PMID- 21970376 TI - Organic dyes containing a coplanar indacenodithiophene bridge for high performance dye-sensitized solar cells. AB - A series of new organic dyes exploiting coplanar indacenodithiophene as the central pi-spacer of the classical donor-(pi-spacer)-acceptor configuration were synthesized and characterized for dye-sensitized solar cells. The coplanarity of the indacenodithiophene core facilitates efficient donor to acceptor charge transfer, imparting the new organic dyes significant bathochromic shifts and remarkable power conversion efficiencies of up to 6.7% (DTInDT) under AM 1.5G radiation. PMID- 21970377 TI - Phospholipid-sepiolite biomimetic interfaces for the immobilization of enzymes. AB - Biomimetic interfaces based on phosphatidylcholine (PC) assembled to the natural silicate sepiolite were prepared for the stable immobilization of the urease and cholesterol oxidase enzymes. This is an important issue in practical advanced applications such as biocatalysis or biosensing. The supported lipid bilayer (BL PC), prepared from PC adsorption, was used for immobilization of enzymes and the resulting biomimetic systems were compared to several other supported layers including a lipid monolayer (ML-PC), a mixed phosphatidylcholine/octyl galactoside layer (PC-OGal), a cetyltrimethylammonium monolayer (CTA), and also to the bare sepiolite surface. Interfacial characteristics of these layers were investigated with a focus on layer packing density, hydrophilicity/hydrophobicity, and surface charge, which are being considered as key points for enzyme immobilization and stabilization of their biological activity. Cytoplasmic urease and membrane-bound cholesterol oxidase, which served as model enzymes, were immobilized on the different PC-based hybrid materials to probe their biomimetic character. Enzymatic activity was assessed by cyclic voltammetry and UV-vis spectrophotometry. The resulting enzyme/bio-organoclay hybrids were applied as active phase of a voltammetric urea biosensor and cholesterol bioreactor, respectively. Urease supported on sepiolite/BL-PC proved to maintain its enzymatic activity over several months while immobilized cholesterol oxidase demonstrated high reusability as biocatalyst. The results emphasize the good preservation of bioactivity due to the accommodation of the enzymatic system within the biomimetic lipid interface on sepiolite. PMID- 21970378 TI - Temperature dependence of metal-organic heteroepitaxy. AB - The nucleation and growth of 2D layers of tetraphenyl porphyrin molecules on Ag(111) are studied with variable-temperature scanning tunneling microscopy. The organic/metal heteroepitaxy occurs by strict analogy to established principles for metal heteroepitaxy. A hierarchy of energy barriers for diffusion on terraces and along edges and around corners of adislands is established. The temperature is key to activating these barriers selectively, thus determining the shape of the organic aggregates, from a fractal shape at lower temperatures to a compact shape at higher temperatures. The energy barriers for the terrace diffusion of porpyrins and the molecule-molecule binding energy were determined to be 30 meV < E(terrace) < 60 and 130 meV < E(diss) < 160 meV, respectively, from measurements of island sizes as a function of temperature. This study provides an experimental verification of the validity of current models of epitaxy for the heteroepitaxy of organics and is thus expected to help establish design principles for complex metal-organic hybrid structures. PMID- 21970387 TI - Anti-alpha-Gal antibody titres remain unaffected by the consumption of fermented milk containing Lactobacillus casei in healthy adults. AB - Alpha-Gal is a glycoconjugate present on cell membranes of non-primate mammals and bacteria, but not in humans, who display anti-Gal antibodies (ABs) in high titres. Probiotics contain bacterial strains which colonize the intestinal tract. In the present study, we investigated whether intake of fermented milk containing Lactobacillus casei (FML) affects anti-Gal AB titres. Serum was drawn from healthy probands (n = 19) for 6 weeks. After the second week, the probands consumed 125 ml of FML per day. Anti-Gal ABs of all isotypes and cytokines were measured. Bacterial cultures were bred from FML and bacteria were stained for alpha-Gal. Concentration of bacteria in FML was manifold higher than in conventional yoghurt (2 * 10(5)/g yoghurt vs. 1.1 * 10(7)/g FML). Both stained highly positive for Alpha-Gal. Alpha-Gal-specific ABs and cytokines remained unaffected by FML intake. Our results indicated that the consumption of FML does not elicit a humoral immune response in healthy adults. PMID- 21970388 TI - Risk factors for re-exploration due to bleeding after coronary artery bypass grafting. AB - OBJECTIVE: The study aimed to investigate relevant clinical risk factors for re exploration due to bleeding after primary coronary artery bypass graft (CABG) surgery, and to evaluate the influence of antiplatelet and antifibrinolytic drugs. DESIGN: Three retrospective analyses were performed on patients who underwent CABG: (1) Logistic regression was used to identify clinical risk factors for re-exploration (n = 3000). (2) A case-control study (n = 228) was used to obtain information on exposure of antithrombotic and hemostatic therapy. (3) Based on exposure to antiplatelet and antifibrinolytic therapy, and odds ratios (ORs) in multivariate logistic models, the proportion of re-explorations attributed to these drugs was calculated. RESULTS: A receiver operating characteristic curve was created for clinical risk factors. The C-index was 0.64, indicating limited ability to predict re-exploration for bleeding. Clopidogrel was the only drug influencing the risk of re-exploration (OR 3.2, 95% CI 1.7 5.9). The harmful effect of clopidogrel was confirmed in multivariate model (OR 4.7, 95% CI 2.2-9.9), and aprotinin had a protective effect of the same magnitude (OR 0.2, 95% CI 0.1-0.6). CONCLUSIONS: Clopidogrel is an essential risk factor for re-exploration due to bleeding, and attributable to at least one-quarter of surveyed cases. Aside from pharmaceuticals, there are no strong clinical risk factors. PMID- 21970398 TI - Masked emotional priming beyond global valence activations. AB - An immense body of research demonstrates that emotional facial expressions can be processed unconsciously. However, it has been assumed that such processing takes place solely on a global valence-based level, allowing individuals to disentangle positive from negative emotions but not the specific emotion. In three studies, we investigated the specificity of emotion processing under conditions of limited awareness using a modified variant of an affective priming task. Faces with happy, angry, sad, fearful, and neutral expressions were presented as masked primes for 33 ms (Study 1) or 14 ms (Studies 2 and 3) followed by emotional target faces (Studies 1 and 2) or emotional adjectives (Study 3). Participants' task was to categorise the target emotion. In all three studies, discrimination of targets was significantly affected by the emotional primes beyond a simple positive versus negative distinction. Results indicate that specific aspects of emotions might be automatically disentangled in addition to valence, even under conditions of subjective unawareness. PMID- 21970400 TI - A simplified technique for ureteral spatulation in laparoscopic pyeloplasty. AB - One of the most difficult, time-consuming, and at the same time critical steps of laparoscopic pyeloplasty is ureteral spatulation. We describe a reproducible technique that greatly simplifies this surgical step. Using standard laparoscopic scissors, the ureter is partially cut just inferior to the ureteropelvic junction (UPJ) at a point where a normal (nonstenotic) ureter is discerned. This first cut involves only half of the circumference of the ureter. The ureter remains attached to the UPJ. Through the most cephalad port, a 5-mm articulating laparoscopic scissors is inserted in the abdomen. The instrument is fully articulated so that the axis of the jaws is almost in line with the ureteral axis. The jaws are opened, one jaw is inserted in the ureteral lumen, and the ureter is spatulated to the requisite length. At this point, the first apical ureteral stitch is placed outside-in while the ureter is stabilized by its remaining attachment to the UPJ. Subsequently, the ureter is freed completely from the UPJ; the UPJ is excised, and the rest of the procedure is performed in a standard fashion. PMID- 21970399 TI - Quantification and visualization of cardiovascular 4D velocity mapping accelerated with parallel imaging or k-t BLAST: head to head comparison and validation at 1.5 T and 3 T. AB - BACKGROUND: Three-dimensional time-resolved (4D) phase-contrast (PC) CMR can visualize and quantify cardiovascular flow but is hampered by long acquisition times. Acceleration with SENSE or k-t BLAST are two possibilities but results on validation are lacking, especially at 3 T. The aim of this study was therefore to validate quantitative in vivo cardiac 4D-acquisitions accelerated with parallel imaging and k-t BLAST at 1.5 T and 3 T with 2D-flow as the reference and to investigate if field strengths and type of acceleration have major effects on intracardiac flow visualization. METHODS: The local ethical committee approved the study. 13 healthy volunteers were scanned at both 1.5 T and 3 T in random order with 2D-flow of the aorta and main pulmonary artery and two 4D-flow sequences of the heart accelerated with SENSE and k-t BLAST respectively. 2D image planes were reconstructed at the aortic and pulmonary outflow. Flow curves were calculated and peak flows and stroke volumes (SV) compared to the results from 2D-flow acquisitions. Intra-cardiac flow was visualized using particle tracing and image quality based on the flow patterns of the particles was graded using a four-point scale. RESULTS: Good accuracy of SV quantification was found using 3 T 4D-SENSE (r2 = 0.86, -0.7 +/- 7.6%) and although a larger bias was found on 1.5 T (r2 = 0.71, -3.6 +/- 14.8%), the difference was not significant (p = 0.46). Accuracy of 4D k-t BLAST for SV was lower (p < 0.01) on 1.5 T (r2 = 0.65, -15.6 +/- 13.7%) compared to 3 T (r2 = 0.64, -4.6 +/- 10.0%). Peak flow was lower with 4D-SENSE at both 3 T and 1.5 T compared to 2D-flow (p < 0.01) and even lower with 4D k-t BLAST at both scanners (p < 0.01). Intracardiac flow visualization did not differ between 1.5 T and 3 T (p = 0.09) or between 4D-SENSE or 4D k-t BLAST (p = 0.85). CONCLUSIONS: The present study showed that quantitative 4D flow accelerated with SENSE has good accuracy at 3 T and compares favourably to 1.5 T. 4D flow accelerated with k-t BLAST underestimate flow velocities and thereby yield too high bias for intra-cardiac quantitative in vivo use at the present time. For intra-cardiac 4D-flow visualization, however, 1.5 T and 3 T as well as SENSE or k-t BLAST can be used with similar quality. PMID- 21970401 TI - Growth characterisation of intra-thoracic organs of children on CT scans. AB - This paper analyses the geometry of intra-thoracic organs from computed tomography (CT) scans performed on 20 children aged from 4 months to 16 years. The aim is to find the most reliable measurements to characterise the growth of heart and lungs from CT data. Standard measurements available on chest radiographies are compared with original measurements only available on CT scans. These measurements should characterise the growth of organs as well as the changes in their position relative to the thorax. Measurements were considered as functions of age. Quadratic regression models were fitted to the data. Goodness of fit of the models was then evaluated. Positions of organs relative to the thorax have a high variability compared with their changes with age. The length and volume of the heart and lungs as well as the diameter of the thorax fit well to the models of growth. It could be interesting to study these measurements with a larger sample size in order to define growth standards. PMID- 21970402 TI - Molecular modeling of hydrotalcite structure intercalated with transition metal oxide anions: CrO4(2-) and VO4(3-). AB - Molecular dynamics (MD) simulations are used to study the interlayer structure, hydrogen bonding, and energetics of hydration of Mg/Al (2:1 and 4:1) layered double hydroxide (LDH) or hydrotalcite (HT) intercalated with oxymetal anions, CrO(4)(2-), and VO(4)(3-). The ab initio forcefield COMPASS is employed for the simulations. The charge on the oxymetal anions is determined by quantum mechanical density functional theory. The structural behavior of the oxymetal anions in LDH directly relates to the energetic relationships, with electrostatic and H-bonding interactions between the anions, hydroxide sites of the metal hydroxide layers, and the interlayer water molecules. Distinct minima in the hydration energy indicate the presence of energetically well-defined structural states with specific water content. The experimentally identified variability in the retention of the CrO(4)(2-) and VO(4)(3-) is well reflected in the calculations and self-diffusion coefficients obtained from the simulations give insight into the mobility of the intercalated species. PMID- 21970403 TI - Possible interaction between B1 retrotransposon-containing sequences and beta(major) globin gene transcriptional activation during MEL cell erythroid differentiation. AB - Repetitive sequences consist of >50% of mammalian genomic DNAs and among these SINEs (short interspersed nuclear elements), e.g. B1 elements, account for 8% of the mouse genome. In an effort to delineate the molecular mechanism(s) involved in the blockade of the in vitro differentiation program of MEL (murine erythroleukaemia) cells by treatment with methylation inhibitors, we detected a DNA region of 559 bp in chromosome 7 located downstream of the 3'-end of the beta(major) globin gene (designated B1-559) with unique characteristics. We have fully characterized this B1-559 region that includes a B1 element, several repeats of ATG initiation codons and consensus DNA-binding sites for erythroid specific transcription factors NF-E2 (nuclear factor-erythroid-derived 2), GATA-1 and EKLF (erythroid Kruppel-like factor). Fragments derived from B1-559 incubated with nuclear extracts form protein complexes in both undifferentiated and differentiated MEL cells. Transient reporter-gene experiments in MEL and human erythroleukaemia K-562 cells with recombinant constructs containing B1-559 fragments linked to HS-2 (hypersensitive site-2) sequences of human beta-globin gene LCR (locus control region) indicated potential cooperation upon erythropoiesis and globin gene expression. The possible interaction between the B1-559 region and beta(major) globin gene transcriptional activation upon execution of erythroid MEL cell differentiation programme is discussed. PMID- 21970404 TI - Assessment of variation in the Alberta Context Tool: the contribution of unit level contextual factors and specialty in Canadian pediatric acute care settings. AB - BACKGROUND: There are few validated measures of organizational context and none that we located are parsimonious and address modifiable characteristics of context. The Alberta Context Tool (ACT) was developed to meet this need. The instrument assesses 8 dimensions of context, which comprise 10 concepts. The purpose of this paper is to report evidence to further the validity argument for ACT. The specific objectives of this paper are to: (1) examine the extent to which the 10 ACT concepts discriminate between patient care units and (2) identify variables that significantly contribute to between-unit variation for each of the 10 concepts. METHODS: 859 professional nurses (844 valid responses) working in medical, surgical and critical care units of 8 Canadian pediatric hospitals completed the ACT. A random intercept, fixed effects hierarchical linear modeling (HLM) strategy was used to quantify and explain variance in the 10 ACT concepts to establish the ACT's ability to discriminate between units. We ran 40 models (a series of 4 models for each of the 10 concepts) in which we systematically assessed the unique contribution (i.e., error variance reduction) of different variables to between-unit variation. First, we constructed a null model in which we quantified the variance overall, in each of the concepts. Then we controlled for the contribution of individual level variables (Model 1). In Model 2, we assessed the contribution of practice specialty (medical, surgical, critical care) to variation since it was central to construction of the sampling frame for the study. Finally, we assessed the contribution of additional unit level variables (Model 3). RESULTS: The null model (unadjusted baseline HLM model) established that there was significant variation between units in each of the 10 ACT concepts (i.e., discrimination between units). When we controlled for individual characteristics, significant variation in the 10 concepts remained. Assessment of the contribution of specialty to between-unit variation enabled us to explain more variance (1.19% to 16.73%) in 6 of the 10 ACT concepts. Finally, when we assessed the unique contribution of the unit level variables available to us, we were able to explain additional variance (15.91% to 73.25%) in 7 of the 10 ACT concepts. CONCLUSION: The findings reported here represent the third published argument for validity of the ACT and adds to the evidence supporting its use to discriminate patient care units by all 10 contextual factors. We found evidence of relationships between a variety of individual and unit-level variables that explained much of this between-unit variation for each of the 10 ACT concepts. Future research will include examination of the relationships between the ACT's contextual factors and research utilization by nurses and ultimately the relationships between context, research utilization, and outcomes for patients. PMID- 21970405 TI - MiR-125b promotes proliferation and migration of type II endometrial carcinoma cells through targeting TP53INP1 tumor suppressor in vitro and in vivo. AB - BACKGROUND: Our previous studies have identified that miR-125b was overexpressed in type II endometrial carcinoma (EC) cells compared with type I using microRNAs microarray. Although recent studies have shown the important role of miR-125b in several tumors and overexpression of miR-125b in advanced EC, its function in this disease has not yet been defined. In the present study, we tried to confirm the result of microRNAs microarray and further investigated the functions of miR 125b in EC, and tried to find new downstream targets of miR-125b. METHODS: Differential expression of miR-125b was detected between type II EC cells (KLE, AN3CA) with ER negative and type I EC cells (ishikawa, RL95-2) with ER positive by qRT-PCR and northern blotting. The effects of miR-125b of on proliferation, migration, and target protein expression were evaluated by CCK8 assay, wound healing assay, transwell migration assay, western blotting, and Tumorigenicity assays in nude mice. In addition, luciferase reporter plasmid was constructed to demonstrate the direct target of miR-125b. RESULTS: MiR-125b was overexpressed in type II EC cells compared with type I. Exogenous miR-125b expression increased proliferation and migration of ishikawa cells and abrogating expression of miR 125b suppressed proliferation, and migration of AN3CA cells in vitro. In addition, in vivo tumor formation assay confirmed that forced miR-125b expression promoted proliferation potential of ishikawa cells, and tumor suppressor gene Tumor Protein 53-Induced Nuclear Protein 1 (TP53INP1) was identified to be the direct target of miR-125b. CONCLUSIONS: TP53INP1 was newly identified to be the direct downstream target of miR-125b. MiR-125b, which was overexpressed in type II EC cells compared with type I, contributes to malignancy of type II EC possibly through down-regulating TP53INP1. PMID- 21970406 TI - Assessment of proteolytic degradation of the basement membrane: a fragment of type IV collagen as a biochemical marker for liver fibrosis. AB - BACKGROUND: Collagen deposition and an altered matrix metalloproteinase (MMP) expression profile are hallmarks of fibrosis. Type IV collagen is the most abundant structural basement membrane component of tissue, which increases 14 fold during fibrogenesis in the liver. Proteolytic degradation of collagens by proteases produces small fragments, so-called neoepitopes, which are released systemically. Technologies investigating MMP-generated fragments of collagens may provide more useful information than traditional serological assays that crudely measure total protein. In the present study, we developed an ELISA for the quantification of a neoepitope generated by MMP degradation of type IV collagen and evaluated the association of this neoepitope with liver fibrosis in two animal models. METHODS: Type IV collagen was degraded in vitro by a variety of proteases. Mass spectrometric analysis revealed more than 200 different degradation fragments. A specific peptide sequence, 1438'GTPSVDHGFL'1447 (CO4 MMP), in the alpha1 chain of type IV collagen generated by MMP-9 was selected for ELISA development. ELISA was used to determine serum levels of the CO4-MMP neoepitope in two rat models of liver fibrosis: inhalation of carbon tetrachloride (CCl4) and bile duct ligation (BDL). The levels were correlated to histological findings using Sirius red staining. RESULTS: A technically robust assay was produced that is specific to the type IV degradation fragment, GTPSVDHGFL. CO4-MMP serum levels increased significantly in all BDL groups compared to baseline, with a maximum increase of 248% seen two weeks after BDL. There were no changes in CO4-MMP levels in sham-operated rats. In the CCl4 model, levels of CO4-MMP were significantly elevated at weeks 12, 16 and 20 compared to baseline levels, with a maximum increase of 88% after 20 weeks. CO4-MMP levels correlated to Sirius red staining results. CONCLUSION: This ELISA is the first assay developed for assessment of proteolytic degraded type IV collagen, which, by enabling quantification of basement membrane degradation, could be relevant in investigating various fibrogenic pathologies. The CO4-MMP degradation fragment was highly associated with liver fibrosis in the two animal models studied. PMID- 21970407 TI - Tunable infrared absorption and visible transparency of colloidal aluminum-doped zinc oxide nanocrystals. AB - Plasmonic nanocrystals have been attracting a lot of attention both for fundamental studies and different applications, from sensing to imaging and optoelectronic devices. Transparent conductive oxides represent an interesting class of plasmonic materials in addition to metals and vacancy-doped semiconductor quantum dots. Herein, we report a rational synthetic strategy of high-quality colloidal aluminum-doped zinc oxide nanocrystals. The presence of substitutional aluminum in the zinc oxide lattice accompanied by the generation of free electrons is proved for the first time by tunable surface plasmon absorption in the infrared region both in solution and in thin films. PMID- 21970408 TI - Electroporation of the E. coli and S. Aureus membranes: molecular dynamics simulations of complex bacterial membranes. AB - Bacterial membranes are complex organelles composed of a variety of lipid types. The differences in their composition are a key factor in determining their relative permeabilities. The success of antibacterial agents depends upon their interaction with bacterial membranes, yet little is known about the molecular level interactions within membranes of different bacterial species. To address this, we have performed molecular dynamics simulations of two bacterial membranes: the outer membrane of E. coli and the cell membrane of S. aureus . We have retained the chemical complexity of the membranes by considering the details of their lipidic components. We identify the extended network of lipid lipid interactions that stabilize the membranes. Our simulations of electroporation show that the S. aureus cell membrane is less resistant to poration than the E. coli outer membrane. The mechanisms of poration for the two membranes have subtle differences; for the E. coli outer membrane, relative differences in mobilities of the lipids of both leaflets are key in the process of poration. PMID- 21970409 TI - Development of a multi-dimensional measure of resilience in adolescents: the Adolescent Resilience Questionnaire. AB - BACKGROUND: The concept of resilience has captured the imagination of researchers and policy makers over the past two decades. However, despite the ever growing body of resilience research, there is a paucity of relevant, comprehensive measurement tools. In this article, the development of a theoretically based, comprehensive multi-dimensional measure of resilience in adolescents is described. METHODS: Extensive literature review and focus groups with young people living with chronic illness informed the conceptual development of scales and items. Two sequential rounds of factor and scale analyses were undertaken to revise the conceptually developed scales using data collected from young people living with a chronic illness and a general population sample. RESULTS: The revised Adolescent Resilience Questionnaire comprises 93 items and 12 scales measuring resilience factors in the domains of self, family, peer, school and community. All scales have acceptable alpha coefficients. Revised scales closely reflect conceptually developed scales. CONCLUSIONS: It is proposed that, with further psychometric testing, this new measure of resilience will provide researchers and clinicians with a comprehensive and developmentally appropriate instrument to measure a young person's capacity to achieve positive outcomes despite life stressors. PMID- 21970411 TI - HIV as a chronic disease considerations for service planning in resource-poor settings. AB - This paper reviews the healthcare issues facing nations which have a substantial caseload of chronic HIV cases. It considers the challenges of extending antiretroviral coverage to an expanding caseload as supplier price rises and international trade agreements come into force to reduce the availability of affordable antiretrovirals just as the economic downturn restricts donor funding. It goes on to review the importance in this context of supporting adherence to drug regimens in order to preserve access to affordable antiretrovirals for those already on treatment, and of removing key barriers such as patient fees and supply interruptions. The demands of those with chronic HIV for health services other than antiretroviral therapy are considered in the light of the fearful or discriminatory attitudes of non-specialist healthcare staff due to HIV-related stigma, which is linked with the weakness of infection control measures in many health facilities. The implications for prevention strategies including those involving criminalisation of HIV transmission or exposure are briefly summarised for the current context, in which the caseload of those whose chronic HIV infection must be controlled with antiretrovirals will continue to rise for the foreseeable future. PMID- 21970412 TI - Effect of nanoscale SubPc interfacial layer on the performance of inverted polymer solar cells based on P3HT/PC71BM. AB - The effect of a nanoscale boron subphthalocyanine chloride (SubPc) interfacial layer on the performance of inverted polymer solar cells based on poly (3-hexyl thiophene) (P3HT) and [6,6]-phenyl-C(71)-butyric acid methyl ester (PC(71)BM) was studied. When a 1 nm SubPc layer was introduced between the active layer (P3HT:PC(71)BM) and MoO(x) in the device with ITO/ZnO/P3HT:PC(71)BM/SubPc/MoO(x)/Al configuration, the power conversion efficiency (PCE) was increased from 3.42 (without SubPc) to 3.59%. This improvement is mainly attributed to the enhanced open-circuit voltage from 0.62 to 0.64 V. When the Flory-Huggins interaction parameters were estimated from the solubility parameters through the contact angle measurement, it revealed that the interaction between SubPc and PC(71)BM is more attractive than that between SubPc and P3HT at the interface of P3HT:PC(71)BM/SubPc, through which charges are well transported from the active layer to the anode. This is supported by a decrease of the contact resistance from 5.49 (SubPc 0 nm) to 0.94 MOmega cm (SubPc 1 nm). The photoelectron spectra provide another evidence for the enhanced PCE, exhibiting that the 1 nm thick SubPc layer extracts more photoelectrons from the active layer than other thicknesses. PMID- 21970410 TI - Molecular analysis of the differentiation potential of murine mesenchymal stem cells from tissues of endodermal or mesodermal origin. AB - Mesenchymal stem cells (MSCs) have received great attention due to their remarkable regenerative, angiogenic, antiapoptotic, and immunosuppressive properties. Although conventionally isolated from the bone marrow, they are known to exist in all tissues and organs, raising the question on whether they are identical cell populations or have important differences at the molecular level. To better understand the relationship between MSCs residing in different tissues, we analyzed the expression of genes related to pluripotency (SOX2 and OCT-4) and to adipogenic (C/EBP and ADIPOR1), osteogenic (OMD and ALP), and chondrogenic (COL10A1 and TRPV4) differentiation in cultures derived from murine endodermal (lung) and mesodermal (adipose) tissue maintained in different conditions. MSCs were isolated from lungs (L-MSCs) and inguinal adipose tissue (A-MSCs) and cultured in normal conditions, in overconfluence or in inductive medium for osteogenic, adipogenic, or chondrogenic differentiation. Cultures were characterized for morphology, immunophenotype, and by quantitative real-time reverse transcription-polymerase chain reaction for expression of pluripotency genes or markers of differentiation. Bone marrow-derived MSCs were also analyzed for comparison of these parameters. L-MSCs and A-MSCs exhibited the typical morphology, immunophenotype, and proliferation and differentiation pattern of MSCs. The analysis of gene expression showed a higher potential of adipose tissue derived MSCs toward the osteogenic pathway and of lung-derived MSCs to chondrogenic differentiation, representing an important contribution for the definition of the type of cell to be used in clinical trials of cell therapy and tissue engineering. PMID- 21970413 TI - Surface modification of gadolinium oxide thin films and nanoparticles using poly(ethylene glycol)-phosphate. AB - The performance of nanomaterials for biomedical applications is highly dependent on the nature and the quality of surface coatings. In particular, the development of functionalized nanoparticles for magnetic resonance imaging (MRI) requires the grafting of hydrophilic, nonimmunogenic, and biocompatible polymers such as poly(ethylene glycol) (PEG). Attached at the surface of nanoparticles, this polymer enhances the steric repulsion and therefore the stability of the colloids. In this study, phosphate molecules were used as an alternative to silanes or carboxylic acids, to graft PEG at the surface of ultrasmall gadolinium oxide nanoparticles (US-Gd(2)O(3), 2-3 nm diameter). This emerging, high sensitivity "positive" contrast agent is used for signal enhancement in T(1) weighted molecular and cellular MRI. Comparative grafting assays were performed on Gd(2)O(3) thin films, which demonstrated the strong reaction of phosphate with Gd(2)O(3) compared to silane and carboxyl groups. Therefore, PEG-phosphate was preferentially used to coat US-Gd(2)O(3) nanoparticles. The grafting of this polymer on the particles was confirmed by XPS and FTIR. These analyses also demonstrated the strong attachment of PEG-phosphate at the surface of Gd(2)O(3), forming a protective layer on the nanoparticles. The stability in aqueous solution, the relaxometric properties, and the MRI signal of PEG-phosphate covered Gd(2)O(3) particles were also better than those from non-PEGylated nanoparticles. As a result, reacting PEG-phosphate with Gd(2)O(3) particles is a promising, rapid, one-step procedure to PEGylate US-Gd(2)O(3) nanoparticles, an emerging "positive" contrast agent for preclinical molecular and cellular applications. PMID- 21970414 TI - Increasing the antioxidant content of food: a personal view on whether this is possible or desirable. AB - A commonly held belief is that higher intake of antioxidants will promote better health through enhanced antioxidant status and lowered oxidative stress. However, the benefits of antioxidant-rich foods have not been reproduced in supplementation trials with pure antioxidants. This has driven research and commercial interest in foods, including traditional foods and their components, with enhanced antioxidant content and improved antioxidant bioavailability, which in many cases is very low. In this paper, evidence for the health benefits of antioxidant-rich foods and methods to increase the antioxidant content and bioavailability of food antioxidants are reviewed briefly, and the concept that increased food antioxidant content/intake per se is beneficial is examined from a cautionary perspective, considering issues of low bioavailability, rapid catabolism, biotransformation and the paradoxical pro-oxidant effects of dietary antioxidants. PMID- 21970415 TI - Zinc(II) complexes with a versatile multitopic tetrazolate-based ligand showing various structures: impact of reaction conditions on the final product structures. AB - Four new zinc(II) complexes based on the same ligand, {Zn(ptp)(H(2)O)](2) (1), [Zn(ptp)(CH(3)OH)](n) (2), [Zn(ptp)](n) (3), and {[Zn(3)(ptp)(3)](DMF)(2)(H(2)O)}(n) (4) [H(2)ptp = 2,3-bis(pyridine-2-yl)-5,6-di 1H-tetrazol-5-ylpyrazine], have been synthesized by solvothermal methods. All of the complexes have been structurally characterized by elemental analysis, IR, powder X-ray diffraction, and single-crystal X-ray diffraction. Structural analyses show that complex 1 possesses a centrosymmetrical neutral dinuclear structure and 2 has 1D right-handed helical chains, with the 2(1) axis expanding along the crystallographic b direction; 3 features a 2D chiral-layered structure with (6,3) net, and complex 4 displays a 3D porous framework with (4,12(2)) topology. The various architectures (0D, 1D, 2D, and 3D) of these four complexes indicated that reaction conditions (temperature and solvent) play an important role in the formation of such coordination structures; namely, various structures can be obtained from the same reactants by controlling and changing the reaction conditions in this system. The luminescent properties of all of the complexes and the corresponding ligand have been investigated in the solid state at room temperature. Moreover, adsorption properties (N(2), H(2), O(2), CO(2), and CH(4)) of the 4a (desolvated 4) have been studied, and the results show that 4a possesses a moderate capability of gas sorption for N(2), H(2), O(2), and CO(2) gases, with high selectivity ratios for O(2) over H(2) at 77 K and CO(2) over CH(4) at 273 K. PMID- 21970416 TI - Dehydrative glycosylation with the Hendrickson reagent. AB - The Hendrickson reagent is able to perform efficiently dehydrative glycosylation of 1-hydroxyglycosyl donors. The reaction occurs under mild conditions through an anomeric oxophosphonium intermediate detected by nuclear magnetic resonance. Further insight into the mechanism was gained by (18)O labeling of anomeric OH. PMID- 21970417 TI - Neutral histidine and photoinduced electron transfer in DNA photolyases. AB - The two major UV-induced DNA lesions, the cyclobutane pyrimidine dimers (CPD) and (6-4) pyrimidine-pyrimidone photoproducts, can be repaired by the light-activated enzymes CPD and (6-4) photolyases, respectively. It is a long-standing question how the two classes of photolyases with alike molecular structure are capable of reversing the two chemically different DNA photoproducts. In both photolyases the repair reaction is initiated by photoinduced electron transfer from the hydroquinone-anion part of the flavin adenine dinucleotide (FADH(-)) cofactor to the photoproduct. Here, the state-of-the-art XMCQDPT2-CASSCF approach was employed to compute the excitation spectra of the respective active site models. It is found that protonation of His365 in the presence of the hydroquinone-anion electron donor causes spontaneous, as opposed to photoinduced, coupled proton and electron transfer to the (6-4) photoproduct. The resulting neutralized biradical, containing the neutral semiquinone and the N3'-protonated (6-4) photoproduct neutral radical, corresponds to the lowest energy electronic ground-state minimum. The high electron affinity of the N3'-protonated (6-4) photoproduct underlines this finding. Thus, it is anticipated that the (6-4) photoproduct repair is assisted by His365 in its neutral form, which is in contrast to the repair mechanisms proposed in the literature. The repair via hydroxyl group transfer assisted by neutral His365 is considered. The repair involves the 5'base radical anion of the (6-4) photoproduct which in terms of electronic structure is similar to the CPD radical anion. A unified model of the CPD and (6-4) photoproduct repair is proposed. PMID- 21970420 TI - Paroxetine-induced dysarthria in a 42-year-old man with pathologic laughing. PMID- 21970428 TI - Social anxiety and difficulty disengaging threat: evidence from eye-tracking. AB - Theoretical models of social phobia propose that biased attention contributes to the maintenance of symptoms; however these theoretical models make opposing predictions. Specifically, whereas Rapee and Heimberg (1997) suggested the biases are characterised by hypervigilance to threat cues and difficulty disengaging attention from threat, Clark and Wells (1995) suggested that threat cues are largely avoided. Previous research has been limited by the almost exclusive reliance on behavioural response times to experimental tasks to provide an index of attentional biases. The current study evaluated the relationship between the time-course of attention and symptoms of social anxiety and depression. Forty-two young adults completed a dot-probe task with emotional faces while eye-movement data were collected. The results revealed that increased social anxiety was associated with attention to emotional (rather than neutral) faces over time as well as difficulty disengaging attention from angry expressions; some evidence was found for a relationship between heightened depressive symptoms and increased attention to fear faces. PMID- 21970429 TI - Superparamagnetic iron oxide nanoparticle attachment on array of micro test tubes and microbeakers formed on p-type silicon substrate for biosensor applications. AB - A uniformly distributed array of micro test tubes and microbeakers is formed on a p-type silicon substrate with tunable cross-section and distance of separation by anodic etching of the silicon wafer in N, N-dimethylformamide and hydrofluoric acid, which essentially leads to the formation of macroporous silicon templates. A reasonable control over the dimensions of the structures could be achieved by tailoring the formation parameters, primarily the wafer resistivity. For a micro test tube, the cross-section (i.e., the pore size) as well as the distance of separation between two adjacent test tubes (i.e., inter-pore distance) is typically approximately 1 MUm, whereas, for a microbeaker the pore size exceeds 1.5 MUm and the inter-pore distance could be less than 100 nm. We successfully synthesized superparamagnetic iron oxide nanoparticles (SPIONs), with average particle size approximately 20 nm and attached them on the porous silicon chip surface as well as on the pore walls. Such SPION-coated arrays of micro test tubes and microbeakers are potential candidates for biosensors because of the biocompatibility of both silicon and SPIONs. As acquisition of data via microarray is an essential attribute of high throughput bio-sensing, the proposed nanostructured array may be a promising step in this direction. PMID- 21970430 TI - Incidence of medication errors in a Moroccan medical intensive care unit. AB - BACKGROUND: Medication errors (ME) are an important problem in all hospitalized populations, especially in intensive care unit (ICU). The aim of the study was to determine incidence, type and consequences of ME. MATERIALS AND METHODS: Prospective observational cohort study during six weeks in a Moroccan ICU. Were included all patients admitted for > 24 hours. ME were collected by two reviewers following three methods: voluntary and verbally report by medical and paramedical staff, chart review and studying prescriptions and transcriptions. Seriousness of events was classified from Category A: circumstances or events that have the capacity to cause error, to Category I: patient's death. RESULTS: 63 patients were eligible with a total of 509 patient-days, and 4942 prescription. We found 492 ME, which incidence was 10 per 100 orders and 967 per 1000 patient-days. There were 113 potential Adverse Drug Events (ADEs) [2.28 per 100 orders and 222 per 1000 patient-days] and 8 ADEs [0.16 per 100 orders and 15.7 per 1000 patient days]. MEs occurred in transcribing stage in 60%cases. Antibiotics were the drug category in 33%. Two ADEs conducted to death. CONCLUSION: MEs are common in Moroccan medical ICU. These results suggest future targets of prevention strategies to reduce the rate of ME. PMID- 21970431 TI - Obesity and nutrition behaviours in Western and Palestinian outpatients with severe mental illness. AB - BACKGROUND: While people with severe mental illness have been found to be more overweight and obese in Western nations, it is unknown to what extent this occurs in Middle Eastern nations and which eating behaviours contribute to obesity in Middle Eastern nations. METHOD: A total of 665 responses were obtained from patients with serious mental illness attending out-patient clinics in Western developed countries (Germany, UK and Australia; n = 518) and Palestine (n = 147). Patients were evaluated by ICD-10 clinical diagnosis, anthropometric measurements and completed a self-report measure of frequencies of consuming different food items and reasons for eating. Nutritional habits were compared against a Western normative group. RESULTS: More participants from Palestine were overweight or obese (62%) compared to Western countries (47%). In the Western sample, obese patients reported consuming more low-fat products (OR 2.54, 95% CI 1.02-6.33) but also greater eating due to negative emotions (OR 1.84, 95% CI 1.31-2.60) than patients with a healthy body-mass index. In contrast, obese patients from Palestine reported increased consumption of unhealthy snacks (OR 3.73 95% CI 1.16 12.00). CONCLUSION: Patients with mental illness have poorer nutritional habits than the general population, particularly in Western nations. Separate interventions to improve nutritional habits and reduce obesity are warranted between Western nations and Palestine. PMID- 21970432 TI - Time-dependent radiolytic yield of OH* radical studied by picosecond pulse radiolysis. AB - Picosecond pulse radiolysis measurements using a pulse-probe method are performed to measure directly the time-dependent radiolytic yield of the OH(*) radical in pure water. The time-dependent absorbance of OH(*) radical at 263 nm is deduced from the observed signal by subtracting the contribution of the hydrated electron and that of the irradiated empty fused silica cell which presents also a transient absoption. The time-dependent radiolytic yield of OH(*) is obtained by assuming the yield of the hydrated electron at 20 ps equal to 4.2 * 10(-7) mol J( 1) and by assuming the values of the extinction coefficients of e(aq)(-) and OH(*) at 782 nm (epsilon(lambda=782 nm) = 17025 M(-1) cm(-1)) and at 263 nm (epsilon(lambda=263 nm) = 460 M(-1) cm(-1)), respectively. The value of the yield of OH(*) radical at 10 ps is found to be (4.80 +/- 0.12) * 10(-7) mol J(-1). PMID- 21970434 TI - Sex chromosome polymorphisms in Arctic charr and their evolutionary origins. AB - Current data on the Y-specific sex-determining region of salmonid fishes from genera Salvelinus, Salmo, and Oncorhynchus indicate variable polymorphisms in the homologous chromosomal locations of the sex-specific determining region. In the majority of the Atlantic lineage Arctic charr, including populations from the Fraser River, in Labrador Canada, as well as Swedish and Norwegian strains, the sex-determining locus maps to linkage group AC-4. Previously, sex-linked polymorphisms (i.e., variation in the associated sex-linked markers on AC-4) have been described in Arctic charr. Here, we report further evidence for intraspecific sex linkage group polymorphisms in Arctic charr (i.e., the detection of the SEX locus on either the AC-1 or AC-21 linkage group) and a possible conservation of a sex linkage arrangement in Icelandic Arctic charr and Atlantic salmon, involving sex-linked markers on the AC-1/21 homeologs and the European AS-1/6 homeologous linkage groups in Atlantic salmon. The evolutionary origins for the multiple sex-determining regions within the salmonid family are discussed. We also relate the variable sex-determining regions in salmonids to their ancestral proto-teleost karyotypic origins and compare these findings with what has been observed in other teleost species in general. PMID- 21970433 TI - Malaria knowledge and long-lasting insecticidal net use in rural communities of central Cote d'Ivoire. AB - BACKGROUND: To improve effectiveness of malaria control interventions, it is essential to deepen the knowledge of contextual factors that govern people's practice for preventive and curative measures. The aim of this study was to determine factors that influence the use of long-lasting insecticidal nets (LLINs) in three rural communities of Cote d'Ivoire, two of which benefited from recent interventions. METHODS: The study was carried out in 957 households in three villages (Bozi, N'Dakonankro and Yoho) located in central Cote d'Ivoire. Indicators of socioeconomic position (SEP), malaria knowledge and practice, placing special emphasis on LLINs, were investigated during a cross-sectional questionnaire survey. Principal component analysis was used to calculate the SEP of households by means of a list of household assets ownership. The concentration index was used to assess the direction of the association between SEP and a given variable. To compare groups or means, Fisher's exact test, chi2 and Kruskal Wallis test were used, as appropriate. RESULTS: Significant differences were found between SEP and reported malaria symptoms, such as fever or hot body, convulsion, anaemia and jaundice (yellow eyes). Individuals from the least poor group cited more often the use of bed nets and insecticide-treated nets (ITNs) compared to poorer groups. The mean number of individuals reporting the use of bed nets and LLINs was different between groups with different educational level. Moreover, the mean number of LLINs in a household was influenced by the presence of children below five years of age. CONCLUSION: The study not only confirmed that education and SEP play important roles in the prevention and control of malaria and promotion of health in general, but pointed at the basic essential knowledge and the key behavioural elements that should guide education and learning processes among the poorer segments of the population. In turn, such knowledge may change behaviour and lead to an increased utilization of LLINs. PMID- 21970435 TI - Fibronectin promotes proplatelet formation in the human megakaryocytic cell line UT-7/TPO. AB - We investigated PPF (proplatelet formation) in the human megakaryocytic cell line UT-7/TPO in vitro and signal transduction pathways responsible for PPF. The megakaryocytic cell lines are useful for studying megakaryocyte biology, although PPF is induced only in the presence of phorbol ester. TPO (thrombopoietin) stimulates megakaryocyte proliferation and differentiation; however, no PPF occurred in the megakaryocytic cell lines, even after the addition of TPO. Therefore, factors other than TPO may play an important role in the process of PPF. As PPF occurs in the bone marrow in vivo, we noted extracellular matrix proteins and found that soluble FN (fibronectin) induced potent PPF in UT-7/TPO without phorbol ester. A Western blot analysis showed that the expression of integrins was not increased by FN treatment. Anti-beta1 antibody and the RGD (arginine-glycine-aspartate) peptide inhibited FN-induced PPF. This result indicates that the signal originated from integrin beta1, which is essential to inducing PPF in UT-7/TPO. Results of the experiments using several inhibitors suggest that activation of the MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase]-ERK and PI3K (phosphoinositide 3 kinase) pathways are necessary for PPF. The phosphorylation of ERK gradually increased for 2 h after the addition of soluble FN, which suggests that activation of ERK is essential for the initial induction of FN-induced PPF in UT 7/TPO. UT-7/TPO is a useful cell line that enables us to study the signals of PPF without effects of chemical compounds. PMID- 21970436 TI - Multiple diffusion pathways in Pluronic F127 mesophases revealed by single molecule tracking and fluorescence correlation spectroscopy. AB - Single molecule tracking (SMT) and fluorescence correlation spectroscopy (FCS) are used to investigate probe molecule diffusion within the mesophase structures of Pluronic F127 gels. Mixtures are prepared in the hexagonal, lamellar, and cubic regions of the ternary F127/water/butanol phase diagram and are doped with nanomolar concentrations of a perylene diimide dye (DTPDI). Flow aligned F127 gels comprised of hexagonally arranged cylindrical micelles exhibit distinct one dimensional (1D) DTPDI motion in wide-field videos, with diffusion occurring parallel to the flow alignment direction. The slow 1D dye motion observed is attributed to single molecule diffusion within the viscous, hydrophobic micelle cores. FCS data acquired from the same samples reveal a bimodal distribution of diffusion coefficients with the slower component assigned to 1D motion in the micelle core and the faster component to 3D diffusion in the interconnected micelle coronas. The rate of diffusion for both components increases with decreasing F127 concentration, reflecting a decrease in gel microviscosity. SMT data from the lamellar and cubic mesophases depict isotropic 2D and 3D diffusion, respectively, and provide supporting evidence for the role of the micelle core and corona in governing diffusion. Trajectory angle distributions from 1D diffusing species in the hexagonal mesophase provide quantitative information on the alignment of the cylindrical micelles. These results, and the rare observation of misaligned trajectories, indicate the hexagonal phase is highly ordered. PMID- 21970437 TI - Avian-induced pluripotent stem cells derived using human reprogramming factors. AB - Avian species are important model animals for developmental biology and disease research. However, unlike in mice, where clonal lines of pluripotent stem cells have enabled researchers to study mammalian gene function, clonal and highly proliferative pluripotent avian cell lines have been an elusive goal. Here we demonstrate the generation of avian induced pluripotent stem cells (iPSCs), the first nonmammalian iPSCs, which were clonally isolated and propagated, important attributes not attained in embryo-sourced avian cells. This was accomplished using human pluripotency genes rather than avian genes, indicating that the process in which mammalian and nonmammalian cells are reprogrammed is a conserved process. Quail iPSCs (qiPSCs) were capable of forming all 3 germ layers in vitro and were directly differentiated in culture into astrocytes, oligodendrocytes, and neurons. Ultimately, qiPSCs were capable of generating live chimeric birds and incorporated into tissues from all 3 germ layers, extraembryonic tissues, and potentially the germline. These chimera competent qiPSCs and in vitro differentiated cells offer insight into the conserved nature of reprogramming and genetic tools that were only previously available in mammals. PMID- 21970438 TI - Colorimetric detection of trace copper ions based on catalytic leaching of silver coated gold nanoparticles. AB - A colorimetric, label-free, and nonaggregation-based silver coated gold nanoparticles (Ag/Au NPs) probe has been developed for detection of trace Cu(2+) in aqueous solution, based on the fact that Cu(2+) can accelerate the leaching rate of Ag/Au NPs by thiosulfate (S(2)O(3)(2-)). The leaching of Ag/Au NPs would lead to dramatic decrease in the surface plasmon resonance (SPR) absorption as the size of Ag/Au NPs decreased. This colorimetric strategy based on size dependence of nanoparticles during their leaching process provided a highly sensitive (1.0 nM) and selective detection toward Cu(2+), with a wide linear detection range (5-800 nM) over nearly 3 orders of magnitude. The cost-effective probe allows rapid and sensitive detection of trace Cu(2+) ions in water samples, indicating its potential applicability for the determination of copper in real samples. PMID- 21970439 TI - Mutifuntional GdPO4:Eu3+ hollow spheres: synthesis and magnetic and luminescent properties. AB - Mondispersed submicrometer GdPO(4):Eu(3+) hollow spheres were synthesized via an effective one-pot hydrothermal process. These hollow spheres have the average diameter of 200 nm, and the shell thickness is about 20 nm. The surface of the spheres consists of a number of nanorods with diameters of about 10 nm and lengths of about 50-80 nm. Both magnetic and luminescent properties of the obtained Eu(3+)-doped GdPO(4) hollow spheres were investigated. The hysteresis plot (M-H) analysis result indicates their paramagnetic property. The fluorescence spectra demonstrate that they emit orange-red color light originated from the (5)D(0) -> (7)F(J) transitions of the Eu(3+) ions. Therefore, the obtained GdPO(4) hollow spheres hold promise for encapsulate drugs with controlled release. Moreover, the GdPO(4):Eu(3+) hollow spheres are attributes for bimodal magnetic resonance imaging (MRI)/optical bioimaging labeling. PMID- 21970440 TI - Consultation etiquette in general practice: a qualitative study of what makes it different for lay cancer caregivers. AB - BACKGROUND: It is commonplace for lay caregivers to overlook their own health concerns when supporting someone with advanced cancer. During this time, caregivers' needs as patients are often marginalised by health professionals, including General Practitioners (GPs), who may miss the breadth of caregivers' needs by focusing on the practicalities of caregiving. GPs traditionally rely on patients to raise their concerns, and then respond to these concerns, but caregivers as patients may be disinclined to cue their GP. The norms of engagement when caregivers consult their GP are less defined, and how they interact with their GP regarding their own health is under-explored. This sub study investigates the norms, assumptions and subtleties which govern caregiver GP consultations, and explores factors affecting their interaction regarding caregivers' own health concerns. METHODS: We conducted semi-structured interviews with six lay caregivers and 19 health professionals in Brisbane, Australia, and analyzed the interview transcripts thematically. RESULTS: Traditional norms of engagement are subjected to assumptions and expectations which caregivers and GPs bring to the consultation. Practice pressures also influence both parties' capacity and willingness to discuss caregivers' health. Nonetheless, some GPs monitor caregivers' health opportunistically. Their interaction is enhanced by the quality of the caregiver-GP relationship and by the GP's skills. CONCLUSIONS: Caregivers are caught in a paradox whereby their health needs may become subsumed by the care recipient's needs in a setting where patient needs are normally scrutinised and supported. Caregivers may not raise their health concerns with their GP, who instead may need to cue them that it is timely and safe to do so. The routine use of a prompt may help to address caregivers' needs systematically, but it needs to be complemented by GPs' desire and capacity to engage with patients in a caregiving role. The potential difference GPs can make to the health of these patients is substantial. PMID- 21970441 TI - Reply to comment on water droplet motion control on superhydrophobic surfaces: exploiting the Wenzel-to-Cassie transition. PMID- 21970443 TI - Strong ligand-protein interactions revealed by ultrafast infrared spectroscopy of CO in the heme pocket of the oxygen sensor FixL. AB - In heme-based sensor proteins, ligand binding to heme in a sensor domain induces conformational changes that eventually lead to changes in enzymatic activity of an associated catalytic domain. The bacterial oxygen sensor FixL is the best studied example of these proteins and displays marked differences in dynamic behavior with respect to model globin proteins. We report a mid-IR study of the configuration and ultrafast dynamics of CO in the distal heme pocket site of the sensor PAS domain FixLH, employing a recently developed method that provides a unique combination of high spectral resolution and range and high sensitivity. Anisotropy measurements indicate that CO rotates toward the heme plane upon dissociation, as is the case in globins. Remarkably, CO bound to the heme iron is tilted by ~30 degrees with respect to the heme normal, which contrasts to the situation in myoglobin and in present FixLH-CO X-ray crystal structure models. This implies protein-environment-induced strain on the ligand, which is possibly at the origin of a very rapid docking-site population in a single conformation. Our observations likely explain the unusually low affinity of FixL for CO that is at the origin of the weak ligand discrimination between CO and O(2). Moreover, we observe orders of magnitude faster vibrational relaxation of dissociated CO in FixL than in globins, implying strong interactions of the ligand with the distal heme pocket environment. Finally, in the R220H FixLH mutant protein, where CO is H-bonded to a distal histidine, we demonstrate that the H-bond is maintained during photolysis. Comparison with extensively studied globin proteins unveils a surprisingly rich variety in both structural and dynamic properties of the interaction of a diatomic ligand with the ubiquitous b-type heme-proximal histidine system in different distal pockets. PMID- 21970444 TI - Estimation of Mayr electrophilicity with a quantitative structure-property relationship approach using empirical and DFT descriptors. AB - Quantitative structure-property relationships (QSPRs) were investigated for the estimation of the Mayr electrophilicity parameter using a data set of 64 compounds, all currently available uncharged electrophiles in Mayr's Database of Reactivity Parameters. Three collections of empirical descriptors were employed, from Dragon, Adriana.Code, and CDK. Models were built with multilinear regressions, k nearest neighbors, model trees, random forests, support vector machines (SVMs), associative neural networks, and counterpropagation neural networks. Quantum chemical descriptors were calculated with density functional theory (DFT) methods and incorporated in QSPR models. The best results were achieved with SVM using seven empirical and DFT descriptors; an R(2) of 0.92 was obtained for the test set (21 compounds). The final seven descriptors were the Parr electrophilicity index, epsilon(LUMO), hardness, and four CDK descriptors (FNSA-3, ATSc5, Kier2, and nAtomLAC). Screening of correlations between individual descriptors and Mayr electrophilicity revealed the highest absolute value of correlation for DFT epsilon(LUMO) (R = -0.82) and comparable correlations for some empirical descriptors, e.g., Dragon's folding degree index (R = -0.80), Kier flexibility index (R = -0.78), and Kier S2K index (R = -0.78). High correlations were observed in the training set between reactivity descriptors calculated by the PM6 semiempirical and DFT methods (R = 0.96 for epsilon(LUMO) and 0.94 for the electrophilicity index). PMID- 21970442 TI - Sequence variability of Rhizobiales orthologs and relationship with physico chemical characteristics of proteins. AB - BACKGROUND: Chromosomal orthologs can reveal the shared ancestral gene set and their evolutionary trends. Additionally, physico-chemical properties of encoded proteins could provide information about functional adaptation and ecological niche requirements. RESULTS: We analyzed 7080 genes (five groups of 1416 orthologs each) from Rhizobiales species (S. meliloti, R. etli, and M. loti, plant symbionts; A. tumefaciens, a plant pathogen; and B. melitensis, an animal pathogen). We evaluated their phylogenetic relationships and observed three main topologies. The first, with closer association of R. etli to A. tumefaciens; the second with R. etli closer to S. meliloti; and the third with A. tumefaciens and S. meliloti as the closest pair. This was not unusual, given the close relatedness of these three species. We calculated the synonymous (dS) and nonsynonymous (dN) substitution rates of these orthologs, and found that informational and metabolic functions showed relatively low dN rates; in contrast, genes from hypothetical functions and cellular processes showed high dN rates. An alternative measure of sequence variability, percentage of changes by species, was used to evaluate the most specific proportion of amino acid residues from alignments. When dN was compared with that measure a high correlation was obtained, revealing that much of evolutive information was extracted with the percentage of changes by species at the amino acid level. By analyzing the sequence variability of orthologs with a set of five properties (polarity, electrostatic charge, formation of secondary structures, molecular volume, and amino acid composition), we found that physico-chemical characteristics of proteins correlated with specific functional roles, and association of species did not follow their typical phylogeny, probably reflecting more adaptation to their life styles and niche preferences. In addition, orthologs with low dN rates had residues with more positive values of polarity, volume and electrostatic charge. CONCLUSIONS: These findings revealed that even when orthologs perform the same function in each genomic background, their sequences reveal important evolutionary tendencies and differences related to adaptation. PMID- 21970445 TI - Delicate dances: immigrant workers' experiences of injury reporting and claim filing. AB - INTRODUCTION: Immigrants often come to Canada for the purpose of employment and make up a large proportion of our labour force. Yet, these workers' labour market experience may not always be positive - new immigrant workers can have difficulties finding a job in their field and may end up working in 'survival jobs' that expose them to workplace hazards. Workers who are new to Canada may not be familiar with legislation designed to protect them at work or with social programs that can help after a work-related injury. METHODS: Through a series of in-depth interviews this study examined the experiences of new immigrants after they were injured on the job. RESULTS: The analysis revealed that many workers were in manual, 'survival jobs' and had not received job or occupational health and safety training. Many did not speak the English language well and knew little about their rights. While workers often felt trepidation about reporting their injury, most told a health care provider or employer that they were injured or in pain. This, however, rarely led to timely or appropriate claim filing. Workers were often discouraged from filing a claim, misinformed about their rights or offered 'time off work' in lieu of reporting the injury to worker's compensation. In instances where a claim was filed, communication problems were common and led to mistakes being made on forms and misunderstandings with the adjudicator and employer. Interpretation services were not always offered consistently or at the correct time. CONCLUSION: Efforts must be made to systematically inform new immigrants of their health and safety rights, responsibilities and entitlements as they are entering the labour market. Systems must be put in place to ensure that immigrants can access the compensation system in the event of a work-related injury and that employers and healthcare providers fulfil their reporting responsibilities. PMID- 21970446 TI - Bioactive compounds extracted from Indian wild legume seeds: antioxidant and type II diabetes-related enzyme inhibition properties. AB - Seven different wild legume seeds (Acacia leucophloea, Bauhinia variegata, Canavalia gladiata, Entada scandens, Mucuna pruriens, Sesbania bispinosa and Tamarindus indica) from various parts of India were analyzed for total free phenolics, l-Dopa (l-3,4 dihydroxyphenylalanine), phytic acid and their antioxidant capacity (ferric-reducing antioxidant power [FRAP] and 2,2-diphenyl-1 picrylhydrazyl [DPPH] assay) and type II diabetes-related enzyme inhibition activitiy (alpha-amylase). S. bispinosa had the highest content in both total free phenolics and l-Dopa, and relatively low phytic acid when compared with other seeds. Phytic acid content, being highest in E. scandens, M. pruriens and T. indica, was highly predictive for FRAP (r = 0.47, p < 0.05) and DPPH (r = 0.66, p < 0.001) assays. The phenolic extract from T. indica and l-Dopa extract from E. scandens showed significantly higher FRAP values among others. All seed extracts demonstrated a remarkable reducing power (7-145 mM FeSO4 per mg extract), DPPH radical scavenging activity (16-95%) and alpha-amylase enzyme inhibition activity (28-40%). PMID- 21970447 TI - Endurance and resistance training lowers C-reactive protein in young, healthy females. AB - The purpose of this study was to determine whether endurance (E) or endurance + resistance (ER) training affects C-reactive protein (CRP) and if these changes are related to alterations in fitness and (or) body composition in young females. Thirty-eight females (aged 18-24 years) were assigned to 1 of 3 groups: (1) E, (2) ER or (3) active control (AC). The E and ER groups completed 15 weeks of marathon training. The ER group performed additional resistance training and the AC group maintained their usual exercise routine. Primary outcomes were measured pre- and post-training and included anthropometric indices, dual-energy x-ray absorptiometry, plasma CRP, time to complete 1.5 miles (in minutes), and upper and lower body strength tests (i.e., 8 repetition max on bench and leg press (ER group only)). There were no differences in any variable among the groups at baseline. After training, the E group decreased time to complete 1.5 miles (p < 0.05). The AC group decreased percent and absolute body fat while the E group decreased percent body fat, absolute body fat, and android and gynoid body fat (p < 0.05). The ER group significantly improved strength (p < 0.001) and reduced plasma CRP from 2.0 +/- 1.1 to 0.8 +/- 0.3 mg.L(-1) (p = 0.03). No significant associations were observed between CRP and measures of body composition or aerobic capacity. Combined endurance and resistance training may be an effective modality for reducing plasma CRP in young adult females independent of changes in aerobic capacity or body composition. PMID- 21970448 TI - Diagnostic assessment of search controls and failure modes in many-objective evolutionary optimization. AB - The growing popularity of multiobjective evolutionary algorithms (MOEAs) for solving many-objective problems warrants the careful investigation of their search controls and failure modes. This study contributes a new diagnostic assessment framework for rigorously evaluating the effectiveness, reliability, efficiency, and controllability of MOEAs as well as identifying their search controls and failure modes. The framework is demonstrated using the recently introduced Borg MOEA, [Formula: see text]-NSGA-II, [Formula: see text]-MOEA, IBEA, OMOPSO, GDE3, MOEA/D, SPEA2, and NSGA-II on 33 instances of 18 test problems from the DTLZ, WFG, and CEC 2009 test suites. The diagnostic framework exploits Sobol's variance decomposition to provide guidance on the algorithms' non-separable, multi-parameter controls when performing a many-objective search. This study represents one of the most comprehensive empirical assessments of MOEAs ever completed. PMID- 21970456 TI - Cytotoxic function of umbilical cord blood natural killer cells: relevance to adoptive immunotherapy. AB - Decreased graft-versus-host disease (GVHD), ease of accessibility, and sustained engraftment encourage the use of umbilical cord blood (UCB) as an alternative source to bone marrow for immune reconstitution in children with leukemia. Natural killer (NK) cells rapidly expand after stem cell transplantation and are important for regulating GVHD and providing graft-versus-leukemia (GVL) effects. This review highlights the phenotypic and functional differences between UCB NK cells and adult peripheral blood (APB) NK cells, and discusses the possible therapeutic benefit of using UCB NK cells for adoptive immunotherapy in leukemia. Alloreactive NK cells show potent cytotoxic activities against human leukocyte antigen (HLA)-nonidentical leukemic cells and reduce leukemia relapses. The higher numbers of NK progenitors in UCB makes it a convenient source for ex vivo expansion of UCB NK cells for posttransplant treatment. UCB NK cells readily respond to interleukin-15, which may greatly enhance their antitumor effect. Activation and expansion protocols for UCB NK cells are currently being developed. PMID- 21970457 TI - Case-based reported mortality associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection in the Netherlands: the 2009-2010 pandemic season versus the 2010-2011 influenza season. AB - BACKGROUND: In contrast to seasonal influenza epidemics, where the majority of deaths occur amongst elderly, a considerable part of the 2009 pandemic influenza related deaths concerned relatively young people. In the Netherlands, all deaths associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection had to be notified, both during the 2009-2010 pandemic season and the 2010-2011 influenza season. To assess whether and to what extent pandemic mortality patterns were reverting back to seasonal patterns, a retrospective analyses of all notified fatal cases associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection was performed. METHODS: The notification database, including detailed information about the clinical characteristics of all notified deaths, was used to perform a comprehensive analysis of all deceased patients with a laboratory-confirmed influenza A(H1N1) 2009 virus infection. Characteristics of the fatalities with respect to age and underlying medical conditions were analysed, comparing the 2009-2010 pandemic and the 2010-2011 influenza season. RESULTS: A total of 65 fatalities with a laboratory-confirmed influenza A(H1N1) 2009 virus infection were notified in 2009-2010 and 38 in 2010-2011. During the pandemic season, the population mortality rates peaked in persons aged 0-15 and 55-64 years. In the 2010-2011 influenza season, peaks in mortality were seen in persons aged 0-15 and 75-84 years. During the 2010-2011 influenza season, the height of first peak was lower compared to that during the pandemic season. Underlying immunological disorders were more common in the pandemic season compared to the 2010-2011 season (p = 0.02), and cardiovascular disorders were more common in the 2010-2011 season (p = 0.005). CONCLUSIONS: The mortality pattern in the 2010-2011 influenza season still resembled the 2009-2010 pandemic season with a peak in relatively young age groups, but concurrently a clear shift toward seasonal patterns was seen, with a peak in mortality in the elderly, i.e. >= 75 years of age. PMID- 21970458 TI - Disruptive selection for sternopleural bristle phenotypes in Drosophila ananassae. AB - Disruptive selection is potentially critical in maintaining variation and initiating speciation and plays an important role in the organization of genetic variability in natural populations. It occurs when extreme phenotypes have a fitness advantage over intermediate phenotypes. Disruptive selection for high and low numbers of sternopleural bristles in Drosophila ananassae was applied for 12 generations to test its effect in induction of behavioural isolation. Pattern of mating between flies of high and low lines was tested in an Elens-Wattiaux mating chamber by using a multiple-choice technique after G(5) and G(12). Data was analyzed by calculating chi(2) under the assumption of random mating to test the difference between homoand heterogamic matings, and sexual isolation was tested by calculating the isolation estimate. The results show that there is no evidence for sexual isolation in G(5) and G(12). The realized heritability, standard error of regression coefficient, and t values suggest that disruptive selection for sternopleural bristle phenotypes was effective, but it does not lead to behavioral isolation in D. ananassae. Rather, it induces differences in mating propensity, which is influenced by sternopleural bristle phenotypes. PMID- 21970459 TI - The current image of single SnO2 nanobelt nanodevice studied by conductive atomic force microscopy. AB - A single SnO2 nanobelt was assembled on a pair of Au electrodes by electric field assembly method. The electronic transport property of single SnO2 nanobelt was studied by conductive atomic force microscopy (C-AFM). Back-to-back Schottky barrier-type junctions were created between AFM tip/SnO2 nanobelt/Au electrode which can be concluded from the I-V curve. The current images of single SnO2 nanobelt nanodevices were also studied by C-AFM techniques, which showed stripes patterns on the nanobelt surface. The current images of the nanobelt devices correlate the microscopy with separate transport properties measurement together. PMID- 21970460 TI - Predictors of in-hospital mortality in elderly patients with bacteraemia admitted to an Internal Medicine ward. AB - BACKGROUND: Infectious diseases are a common cause of increased morbidity and mortality in elderly patients. Bacteraemia in the elderly is a difficult diagnosis and a therapeutic challenge due to age-related vicissitudes and to their comorbidities. The main purpose of the study was to assess independent risk factors for in-hospital mortality among the elderly with bacteraemia admitted to an Internal Medicine Ward. METHODS: Overall, a cohort of 135 patients, 65 years of age and older, with bacteraemia were retrospectively studied. Data related to demographic information, comorbidities, clinical parameters on admission, source and type of infection, microorganism isolated in the blood culture, laboratory data and empirical antibiotic treatment was recorded from each patient. Multivariate logistic regression was performed to identify independent predictors of all-cause in-hospital mortality. RESULTS: Of these 135 patients, 45.9% were women. The most common infections in this group of patients were urinary tract infections (46.7%). The main microorganisms isolated in the blood cultures were Escherichia coli (14.9%), Methicillin-resistant Staphylococcus aureus (MRSA) (12.0%), non-MRSA (11.4%), Klebsiella pneumoniae (9.1%) and Enterococcus faecalis (8.0%). The in-hospital mortality was 22.2%. Independent prognostic factors associated with in-hospital mortality were age >= 85 years, chronic renal disease, bacteraemia of unknown focus and cognitive impairment at admission (OR, 2.812 [95% CI, 1.039-7.611; p = 0.042]; OR, 6.179 [95% CI, 1.840-20.748; p = 0.003]; OR, 8.673 [95% CI, 1.557-48.311; p = 0.014] and OR, 3.621 [95% CI, 1.226 10.695; p = 0.020], respectively). By multivariate analysis appropriate antibiotic therapy was not associated with lower odds of mortality. CONCLUSION: Bacteraemia in the elderly has a high mortality rate. There are no set of signs or clinical features that can predict bacteraemia in the elderly. However, older age (>= 85 years), chronic renal disease, bacteraemia of unknown focus and severe cognitive impairment adversely affects the outcome of elderly patients with bacteraemia admitted to an Internal Medicine ward. PMID- 21970461 TI - Computational study of the binding modes of caffeine to the adenosine A2A receptor. AB - Using the recently solved crystal structure of the human adenosine A(2A) receptor, we applied MM/PBSA to compare the binding modes of caffeine with those of the high-affinity selective antagonist ZM241385. MD simulations were performed in the environment of the lipid membrane bilayer. Four low-energy binding modes of caffeine-A(2A) were found, all of which had similar energies. Assuming an equal contribution of each binding mode of caffeine, the computed binding free energy difference between caffeine and ZM241385 is -2.4 kcal/mol, which compares favorably with the experimental value, -3.6 kcal/mol. The configurational entropy contribution of -0.9 kcal/mol from multiple binding modes of caffeine helps explain how a small molecule like caffeine can compete with a significantly larger molecule, ZM241385, which can form many more interactions with the receptor. We also performed residue-wise energy decomposition and found that Phe168, Leu249, and Ile274 contribute most significantly to the binding modes of caffeine and ZM241385. PMID- 21970462 TI - Transition dipole moments of the Qy band in photosynthetic pigments. AB - From studying the time evolution of the single electron density matrix within a density functional tight-binding formalism we calculate the Q(y) transition dipole moments vector direction and strength for a series of important photosynthetic pigments. We obtain good agreement with first-principles and experimental results and provide insights into the detailed nature of these excitations from the time evolving populations of molecular orbitals involved as well as correlations between pigment chemistry and dipole strength. PMID- 21970464 TI - Toward transparent nanocomposites based on polystyrene matrix and PMMA-grafted CeO2 nanoparticles. AB - The association of transparent polymer and nanosized pigment particles offers attractive optical materials for various potential and existing applications. However, the particles embedded into polymers scatter light due to refractive index (RI) mismatch and reduce transparency of the resulting composite material. In this study, optical composites based on polystyrene (PS) matrix and poly(methyl methacrylate) (PMMA)-grafted CeO(2) hybrid particles were prepared. CeO(2) nanoparticles with an average diameter of 18 +/- 8 nm were precipitated by treating Ce(NO(3)).6H(2)O with urea in the presence of a polymerizable surfactant, 3-methacyloxypropyltrimethoxy silane. PMMA chains were grafted on the surface of the nanoparticles upon free radical in situ solution polymerization. While blending of unmodified CeO(2) particles with PS resulted in opaque films, the transparency of the composite films was remarkably enhanced when prepared by PMMA-grafted CeO(2) hybrid particles, particularly those having a PMMA thickness of 9 nm. The improvement in transparency is presumably due to the reduction in RI mismatch between CeO(2) particles and the PS matrix when using PMMA chains at the interface. PMID- 21970463 TI - Maternal and child health in yushu, qinghai province, china. AB - INTRODUCTION: Surmang, Qinghai Province is a rural nomadic Tibetan region in western China recently devastated by the 2010 Yushu earthquake; little information is available on access and coverage of maternal and child health services. METHODS: A cross-sectional household survey was conducted in August 2004. 402 women of reproductive age (15-50) were interviewed regarding their pregnancy history, access to and utilization of health care, and infant and child health care practices. RESULTS: Women's access to education was low at 15% for any formal schooling; adult female literacy was <20%. One third of women received any antenatal care during their last pregnancy. Institutional delivery and skilled birth attendance were <1%, and there were no reported cesarean deliveries. Birth was commonly attended by a female relative, and 8% of women delivered alone. Use of unsterilized instrument to cut the umbilical cord was nearly universal (94%), while coverage for tetanus toxoid immunization was only 14%. Traditional Tibetan healers were frequently sought for problems during pregnancy (70%), the post partum period (87%), and for childhood illnesses (74%). Western medicine (61%) was preferred over Tibetan medicine (9%) for preventive antenatal care. The average time to reach a health facility was 4.3 hours. Postpartum infectious morbidity appeared to be high, but only 3% of women with postpartum problems received western medical care. 64% of recently pregnant women reported that they were very worried about dying in childbirth. The community reported 3 maternal deaths and 103 live births in the 19 months prior to the survey. CONCLUSIONS: While China is on track to achieve national Millennium Development Goal targets for maternal and child health, women and children in Surmang suffer from substantial health inequities in access to antenatal, skilled birth and postpartum care. Institutional delivery, skilled attendance and cesarean delivery are virtually inaccessible, and consequently maternal and infant morbidity and mortality are likely high. Urgent action is needed to improve access to maternal, neonatal and child health care in these marginalized populations. The reconstruction after the recent earthquake provides a unique opportunity to link this population with the health system. PMID- 21970465 TI - Endothelial dysfunction and increased oxidative stress in mitochondrial diseases. AB - MDs (mitochondrial diseases) are a clinically heterogeneous group of disorders characterized by impairment of the respiratory chain function with altered oxidative phosphorylation. We tested the hypothesis that the function of vascular endothelium is affected by increased oxidative stress in MDs. A total of 12 patients with MDs and pair-matched controls were studied. Endothelial function was assessed by measuring FMD (flow-mediated vasodilation) of brachial and common femoral arteries. The test was repeated after vitamin C (500 mg, twice a day) and E (400 mg, once a day) supplementation for 30 days and 90 days after vitamin withdrawal. FMD was reduced in patients compared with controls [AUC/tau (time averaged area under the curve) for the brachial artery, 1.05+/-0.24 compared with 4.19+/-0.59% respectively, P<0.001; AUC/tau for the femoral artery, 0.98+/-0.19 compared with 2.36+/-0.29% respectively, P=0.001; values are means+/-S.E.M.] and correlated (brachial artery) with plasma lactate (r=-0.63, P<0.01). Urinary 8-iso PGF2alpha (8-iso-prostaglandin F2alpha) was higher in patients than controls (505.6+/-85.9 compared with 302.5+/-38.7 pg/mg of creatinine; P<0.05) and correlated with plasma lactate (r=0.70, P<0.05). Immunohistochemical analysis showed 8-iso-PGF2alpha staining in MD-affected striated muscle cells and in blood vessels in muscle biopsies of patients. Antioxidant vitamins transiently restored FMD in patients [DeltaAUC/tau (change in AUC/tau) for the brachial artery, +1.38+/-0.49%, P<0.05; DeltaAUC/tau for the femoral artery, +0.98+/-0.24%, P<0.01] but had no effect on FMD in controls (brachial artery, -1.3+/-0.63%; and common femoral artery, -0.58+/-0.30%), thus abolishing the differences between patients and controls. The results of the present study indicate that oxidative stress is increased and is, at least partly, responsible for endothelial dysfunction in MDs. PMID- 21970466 TI - Adsorption of RNase A on cationic polyelectrolyte brushes: a study by isothermal titration calorimetry. AB - We present a study of the adsorption of a positively charged protein to a positively charged spherical polyelectrolyte brush (SPB) by isothermal titration calorimetry (ITC). ITC is used to determine the adsorption isotherm as a function of temperature and of salt concentration (at physiological pH 7.2). At low ionic strength, RNase A is strongly adsorbed by the SPB particles despite the fact that both the SPB particles and the protein are positively charged. Virtually no adsorption takes place when the ionic strength is raised through added salt. This is strong evidence for counterion release as the primary driving force for protein adsorption. We calculated that ~2 counterions were released upon RNase A binding. The adsorption of RNase A into like-charged SPB particles is entropy driven, and protein protonation was not significant. Temperature-dependent measurements showed a disagreement between the enthalpy derived via the van't Hoff equation and the calorimetric enthalpy. Further analysis shows that van't Hoff analysis leads to the correct enthalpy of adsorption. The additional contributions to the measured enthalpy are potentially sourced from unlinked equilibria such as conformational changes that do not contribute to the binding equilibrium. PMID- 21970467 TI - Co-morbidity and drug treatment in Alzheimer's disease. A cross sectional study of participants in the dementia study in northern Norway. AB - BACKGROUND: Inappropriate medical treatment of co-morbidities in Alzheimer's disease (AD) is an increasing concern in geriatric medicine. The objective of this study was to compare current drug use related to co-morbidity between individuals with a recent diagnosis of AD and a cognitively healthy control group in a population based clinical trial in Northern Norway. METHODS: SETTING: Nine rural municipalities with 70,000 inhabitants in Northern Norway. PARTICIPANTS: PARTICIPANTS with and without AD recruited in general practice and by population based screening.187 participants with a recent diagnosis of AD were recruited among community dwellers. Of 791 respondents without cognitive symptoms, 500 were randomly selected and invited to further clinical and cognitive testing. The final control group consisted of 200 cognitively healthy individuals from the same municipalities. Demographic characteristics, data on medical history and current medication were included, and a physical and cognitive examination was performed. The statistical analyses were carried out by independent sample t test, chi-square, ANCOVA and logistic regression. RESULTS: A co-morbidity score was significantly higher in AD participants compared to controls. The mean number of drugs was higher for AD participants compared to controls (5.1+/-3.6 and 2.9+/ 2.4 respectively, p<0.001 age and gender adjusted), also when adjusted for co morbidity. AD participants used significantly more anticholinergic, sedative and antidepressant drugs. For nursing home residents with AD the mean number of drugs was significantly higher compared to AD participants living at home (6.9+/-3.9 and 4.5+/-3.3, respectively, p<0.001). CONCLUSIONS: AD participants were treated with a significantly higher number of drugs as compared to cognitively healthy controls, even after adjustment for co-morbidity. An inappropriate use of anticholinergic and sedative drugs was identified, especially among nursing home residents with AD. The drug burden and the increased risk of adverse reactions among individuals suffering from AD need more attention from prescribing doctors. PMID- 21970468 TI - Synthesis of 2H-indazoles by the [3 + 2] dipolar cycloaddition of sydnones with arynes. AB - A rapid and efficient synthesis of 2H-indazoles has been developed using a [3 + 2] dipolar cycloaddition of sydnones and arynes. A series of 2H-indazoles have been prepared in good to excellent yields using this protocol, and subsequent Pd catalyzed coupling reactions can be applied to the halogenated products to generate a structurally diverse library of indazoles. PMID- 21970469 TI - Reduction of surgical site infection using a novel intervention (ROSSINI): study protocol for a randomised controlled trial. AB - BACKGROUND: Surgical site infection (SSI) is a common complication following abdominal surgery. It is associated with considerable morbidity and mortality, and its management results in significant cost to health services within both primary and secondary care. Some surgeons believe that the use of a wound-edge protection device may reduce the incidence of SSI. Whilst there is some encouraging evidence showing that such devices may lead to a reduction in SSI, there are no controlled trials of sufficient size or quality to support their routine use. METHODS/DESIGN: 750 patients will be recruited from around 20 surgical units within the United Kingdom. Patients undergoing laparotomy through any major abdominal incision for any indication, elective or emergency, are eligible. Patients under the age of 18, those undergoing a laparoscopic assisted procedure or who have undergone laparotomy within the previous 3 months, and those who are unable to give informed consent will be excluded. Patients will be randomised (1:1 ratio) to the use of a wound-edge protection device or no wound edge protection device during surgery. Follow up will consist of blinded clinical wound reviews at 5-7 days and 30-33 days postoperatively with a self-completed questionnaire covering the intervening period. Quality of life questionnaires will be completed prior to surgery and at the subsequent wound review points and information on resource usage will also be captured.The primary outcome measure is SSI within 30 days of surgery. Secondary outcomes include the impact of the degree of wound contamination, patient comorbidity, and operative characteristics on the efficacy of a wound-edge protection device in reducing SSI and whether the use of a wound-edge protection device has an effect on health-related quality of life or length of hospital stay and is cost-effective. DISCUSSION: Rossini is the first multicentre observer-blinded randomised controlled trial of sufficient size and quality to establish whether the use of a wound-edge protection device in adult patients undergoing abdominal surgery leads to a lower rate of SSI. The results of this study will be used to inform current surgical practice and may potentially benefit patients undergoing surgery in the future. TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN: ISRCTN40402832. PMID- 21970470 TI - Cellular consequences of copper complexes used to catalyze bioorthogonal click reactions. AB - Copper toxicity is a critical issue in the development of copper-based catalysts for copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions for applications in living systems. The effects and related toxicity of copper on mammalian cells are dependent on the ligand environment. Copper complexes can be highly toxic, can induce changes in cellular metabolism, and can be rapidly taken up by cells, all of which can affect their ability to function as catalysts for CuAAC in living systems. Herein, we have evaluated the effects of a number of copper complexes that are typically used to catalyze CuAAC reactions on four human cell lines by measuring mitochondrial activity based on the metabolism of 3 (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to study toxicity, inductively coupled plasma mass spectrometry to study cellular uptake, and coherent anti-Stokes Raman scattering (CARS) microscopy to study effects on lipid metabolism. We find that ligand environment around copper influences all three parameters. Interestingly, for the Cu(II)-bis-L-histidine complex (Cu(his)(2)), cellular uptake and metabolic changes are observed with no toxicity after 72 h at micromolar concentrations. Furthermore, we show that under conditions where other copper complexes kill human hepatoma cells, Cu(I)-L histidine is an effective catalyst for CuAAC labeling of live cells following metabolic incorporation of an alkyne-labeled sugar (Ac(4)ManNAl) into glycosylated proteins expressed on the cell surface. This result suggests that Cu(his)(2) or derivatives thereof have potential for in vivo applications where toxicity as well as catalytic activity are critical factors for successful bioconjugation reactions. PMID- 21970471 TI - Design, synthesis, and evaluation of a novel dual FMS-like tyrosine kinase 3/stem cell factor receptor (FLT3/c-KIT) inhibitor for the treatment of acute myelogenous leukemia. AB - A high-throughput screen of our compound archive revealed a novel class of dual FMS-like tyrosine kinase 3 (FLT3)/c-KIT inhibitors. With the help of molecular modeling, this class was rapidly optimized for both potency against FLT3 and FLT3/c-KIT and excellent potency in cell-based assays, leading to dose-dependent cell death in acute myelogenous leukemia (AML) patient blast samples. Ultimately, the AML patient blast data defined the preferred target profile as we designed and evaluated a set of FLT3 selective and FLT3/c-KIT dual molecules. Further optimization for pharmacokinetic properties resulted in the selection of the dual FLT3/c-KIT inhibitor, N(3)-(4-(trans-4-morpholinocyclohexyl)phenyl)-1-(pyridin-2 yl)-1H-1,2,4-triazole-3,5-diamine, VX-322 (compound 37), to move forward to preclinical evaluation. PMID- 21970472 TI - Prolongation of the active lifetime of a biomolecular motor for in vitro motility assay by using an inert atmosphere. AB - Over the last few decades, the in vitro motility assay has been performed to probe the biophysical and chemo-mechanical properties as well as the self organization process of biomolecular motor systems such as actin-myosin and microtubule-kinesin. However, aggression of the reactive oxygen species (ROS) and concomitant termination of the activity of biomolecular motors during investigation remains a drawback of this assay. Despite enzymatic protection that makes use of a combination of glucose, glucose oxidase, and catalase, the active lifetime of biomolecular motors is found to be only a few hours and this short lifetime restricts further study on those systems. We have solved this problem by using a newly developed system of the in vitro motility assay that is conducted in an inert nitrogen gas atmosphere free of ROS. Using microtubule-kinesin as a model system we have shown that our system has prolonged the active lifetime of the biomolecular motor until several days and even a week by protecting it from oxidative damage. PMID- 21970473 TI - Fragmentation and site-specific quantification of core fucosylated glycoprotein by multiple reaction monitoring-mass spectrometry. AB - Glycosylation modifications of proteins have been attracting increasing attention due to their roles in the physiological and pathological processes of the cell. Core fucosylation (CF), one special type of glycan structure in glycoproteins, has been linked with tumorigenesis. The study of protein glycosylation has been hindered by the technical challenges caused by the microheterogeneity of glycan modifications. In commonly used methods, sugar chains on the peptide were released using endoglycosidase, and the glycan and peptides were analyzed separately with mass spectrometry. Although mass spectrometric analysis can be performed easily in this way, an increase in false positives when assigning glycosites was inevitable. Our earlier research demonstrated a strategy combining Endo F3-catalyzed partial deglycosylation with MS(3) (MS/MS/MS) scanning triggered by the neutral loss of a fucose to precisely identify CF proteins on a large scale. In this research, fragmentations of partially deglycosylated glycopeptides were studied using a triple quadrupole mass spectrometer, and a quantification method that coupled our published identification strategy with multiple reaction monitoring-mass spectrometry (MRM-MS) analysis was developed to obtain site-specific quantification information of core fucosylated peptides. To illustrate the feasibility of the quantification method, the CF peptides of target proteins in clinical serum were quantified and compared as a preliminary demonstration. PMID- 21970476 TI - Lung carcinoma morphology or mutational profile: that is the question. PMID- 21970477 TI - Selection of residents: is winning only a numbers game? PMID- 21970478 TI - "No pay, no play": the end of professional ethics in pathology? PMID- 21970479 TI - Selected reviews in surgical and molecular pathology: from the Tutorial on Pathology of the GI Tract, Pancreas, And Liver at Weill Cornell Medical College. PMID- 21970480 TI - A clinical and histopathologic focus on Barrett esophagus and Barrett-related dysplasia. AB - CONTEXT: Barrett esophagus is a metaplastic, premalignant lesion associated with approximately 0.5% annual incidence of progression to esophageal adenocarcinoma. Diagnosis and screening of Barrett esophagus and Barrett-related dysplasia relies on histologic evaluation of endoscopic mucosal biopsies, a process that is burdened with interobserver variability. OBJECTIVES: To review the histologic features and classification of Barrett esophagus and Barrett-related dysplasia, to discuss the underlying difficulties in diagnosis and pitfalls, and to provide a brief review of new developments related to therapeutic modalities for patients diagnosed with dysplasia. DATA SOURCES: Sources include a review of relevant literature indexed in PubMed (US National Library of Medicine). CONCLUSIONS: In spite of interobserver variability, histologic assessment of dysplasia is currently the accepted method of surveillance, and subsequent patient management is dictated by this evaluation. Although not universal, endoscopic therapy is increasingly important in replacing esophagectomy for patients with high-grade dysplasia or early carcinoma. PMID- 21970481 TI - Mucinous neoplasms of the appendix and peritoneum. AB - CONTEXT: Appendiceal mucinous neoplasms are considered enigmatic tumors of unpredictable biologic potential. Their importance lies in their potential to spread to the peritoneum and viscera in the form of gelatinous mucin deposits. Extra-appendiceal spread of these tumors is the most common etiology of pseudomyxoma peritonei , which is a descriptive term encompassing a number of neoplastic and nonneoplastic peritoneal disorders. Many studies aimed at evaluating the biologic importance of appendiceal mucinous neoplasms and pseudomyxoma peritonei have employed inconsistent histologic criteria for their diagnosis and descriptive terminology for their classification. As a result, appendiceal mucinous neoplasms and associated peritoneal disease represents one of the most confusing and controversial areas in gastrointestinal pathology. OBJECTIVES: To summarize the literature regarding the biologic potential of appendiceal mucinous neoplasms and pseudomyxoma peritonei and to discuss the similarities and differences between proposed systems for their classification. DATA SOURCES: Literature review and case-derived material. CONCLUSIONS: Many studies have contributed to an increased understanding of the natural progression of mucinous neoplasms of the appendix and peritoneum, and the adoption of a uniform reporting system, as advocated by the American Joint Committee on Cancer and the World Health Organization, will facilitate clear communication among pathologists and clinical colleagues. PMID- 21970482 TI - Microsatellite instability and colorectal cancer. AB - CONTEXT: About 15% of colorectal cancers are characterized by genomic microsatellite instability, and of these, about 1 in 5 (2%-4% overall) are due to Lynch syndrome, a dominantly inherited condition predisposing the patient to cancers of multiple organ systems, including the gastrointestinal tract. Identification of individuals with Lynch syndrome allows for increased surveillance of the affected individual and of potentially affected family members. OBJECTIVE: To review the literature on microsatellite instability in colorectal cancer and current laboratory diagnostic testing strategies for the detection of Lynch syndrome. DATA SOURCES: This review is based on peer-reviewed literature, published guidelines from professional organizations (Evaluation of Genomic Applications in Practice and Prevention Working Group, National Comprehensive Cancer Network), and information from clinical laboratories performing microsatellite instability testing. CONCLUSIONS: Universal screening for Lynch syndrome in all individuals affected with colorectal cancer has been recommended by the Evaluation of Genomic Applications in Practice and Prevention Working Group. Preliminary screening tests can identify individuals unlikely to be affected by Lynch syndrome, thereby reducing the need for full gene analysis. Immunohistochemistry and polymerase chain reaction-based tests for microsatellite instability have similar clinical sensitivity and specificity, and each method has advantages and limitations. BRAF and MLH1 methylation testing are useful reflex tests for those with a defect in MLH1 identified by immunohistochemistry. Emerging technologies, such as high-throughput sequencing, may substantially affect diagnostic algorithms in the future. PMID- 21970483 TI - Epidermal growth factor receptor pathway mutations and colorectal cancer therapy. AB - CONTEXT: Rational anticancer therapy is beginning to expand the practice of surgical pathology beyond a primarily morphologic and immunophenotypic analysis into the molecular arena. Molecular testing of tumors can have both diagnostic and therapeutic value, which guides treatment decisions. This is true for colorectal cancer in which mutations in signaling mediators predict resistance to anti-epidermal growth factor receptor (anti-EGFR) therapy. OBJECTIVE: To review the clinically relevant mutations that currently guide treatment decisions in metastatic colorectal cancer, summarize additional mutations that are expected to improve the prognostic sensitivity of molecular testing, and provide practical suggestions for submitting specimens for molecular analysis. DATA SOURCES: Peer reviewed literature reporting pertinent clinical trial data, mutation analysis, and molecular mechanisms of drug resistance, as well as comprehensive review articles germane to the topic and published testing recommendations from the College of American Pathologists. CONCLUSIONS: Molecular analysis of colorectal cancer is now mandated before initiation of anti-EGFR therapy and directly impacts treatment options and outcomes. Familiarity with the mutations that determine utility and efficacy of therapy, as well as the importance of careful sample selection, will facilitate appropriate testing and optimize patient care. PMID- 21970484 TI - Lymphoproliferative disorders of the gastrointestinal tract: a review and pragmatic guide to diagnosis. AB - CONTEXT: The gastrointestinal tract is the most common site of extranodal lymphomas. Although all histologic categories of malignant lymphoma develop in the gastrointestinal tract, large B-cell lymphomas predominate, followed by extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) type; the latter is especially prevalent in stomach. The acceptance of extranodal marginal zone lymphoma of MALT type as a clinicopathologic entity has reduced the number of cases that formerly were interpreted as florid lymphoid hyperplasia ("pseudolymphoma"). Nonetheless, the distinction of lymphoid hyperplasia from a lymphoma of MALT type in small biopsy specimens remains problematic. OBJECTIVE: To assess the relevant morphologic, immunologic, molecular, and genetic properties of gastrointestinal lymphomas and to present a feasible tactic for diagnosis, expressly for small biopsy specimens. DATA SOURCES: Case-derived material and literature review using PubMed (National Library of Medicine). CONCLUSIONS: Most gastrointestinal lymphomas are readily amenable to an unqualified diagnosis, primarily those cases consisting of monomorphic large cells whether of B- or T-cell lineage, including cases associated with enteropathy. Diagnosis for infiltrates dominated by small lymphocytes remains taxing, as the differential diagnosis embraces not only MALT lymphoma and lymphoid hyperplasia but also mantle cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma. Adherence to strict morphologic criteria is the standard for diagnosis, but these criteria should be augmented by immunologic studies together with judicious use of molecular techniques to determine clonality. In establishing a diagnosis of gastric marginal zone lymphoma of MALT type, determination of t(11;18)(q21;q21) status may be required since this translocation has clinical ramifications. PMID- 21970485 TI - Gastrointestinal stromal tumor: advances in diagnosis and management. AB - CONTEXT: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract and should be differentiated from other mesenchymal tumors. They harbor specific activating mutations in the KIT or platelet-derived growth factor receptor alpha ( PDGFRA ) receptor tyrosine kinases, which makes them responsive to pharmacologic inhibitors, such as imatinib mesylate and sunitinib malate. OBJECTIVES: To provide a comprehensive review of the pathogenesis of GIST and the underlying principles of targeted therapy, to review the salient histologic and immunohistochemical features that facilitate the distinction of GIST from other mesenchymal neoplasms of the gastrointestinal tract, and to present the prognostic parameters for risk stratification that guide clinical management. DATA SOURCES: Review of the English literature through PubMed as well as personal experience. Photographs were taken from cases encountered at the Cleveland Clinic. CONCLUSIONS: The discovery of the KIT -GIST connection has not only improved the diagnostic accuracy of GISTs but also provided us with a better understanding of the histogenesis and molecular pathogenesis of these neoplasms. PMID- 21970486 TI - Benign gastrointestinal mesenchymal BUMPS: a brief review of some spindle cell polyps with published names. AB - CONTEXT: There are several benign, predominantly spindle cell, mesenchymal proliferations involving the mucosa and/or submucosa in the gut, which present as polyps and pathologists see as polypectomy specimens. These include perineuriomas, Schwann cell nodules, ganglioneuromas, leiomyomas of the muscularis mucosae, inflammatory fibroid polyps, and granular cell tumors. OBJECTIVES: To evaluate these mesenchymal polyps for their morphologic, immunohistochemical, ultrastructural, and molecular characteristics and to determine some of their associations. DATA SOURCES: Personal observations based on years of analyzing endoscopic biopsies and a review of the world's literature. CONCLUSIONS: These polyps do surface every so often. There is significant literature covering inflammatory fibroid polyps and granular cell tumors, but there is little literature about the other entities. PMID- 21970487 TI - Liver biopsies in chronic viral hepatitis: beyond grading and staging. AB - CONTEXT: Knowledge of the etiology and pathogenesis of chronic viral hepatitis has grown immensely during the past 50 years. The terminology used to assess liver biopsies with chronic viral hepatitis and the role of the liver biopsy itself have also evolved during this time. Although the focus of much discussion regarding diagnostic assessment of liver biopsies in patients with viral hepatitis has been on grading of activity and staging of fibrosis, each biopsy is also an opportunity to assess many other important features. OBJECTIVES: To discuss opportunities provided by biopsies to assess features such as the presence of virus-associated premalignant or malignancy-related changes, and the presence of other concomitant diseases, including fatty liver disease of diverse causes, and hemochromatosis, hereditary or otherwise. DATA SOURCES: The data were obtained from published literature and professional experience. CONCLUSIONS: The evaluation of liver biopsies with chronic viral hepatitis has evolved beyond grading and staging. Pathologists need to be aware of the other features that may have important clinical implications. PMID- 21970488 TI - Histopathologic characteristics of lung adenocarcinomas with epidermal growth factor receptor mutations in the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society lung adenocarcinoma classification. AB - CONTEXT: The proposed International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of lung adenocarcinomas has been published. OBJECTIVE: To evaluate the correlation between epidermal growth factor receptor mutations and histologic subtypes of lung adenocarcinomas according to the upcoming new classification of lung adenocarcinomas. DESIGN: Medical records and pathologic slides were reviewed for a total of 107 surgically resected lung adenocarcinomas. All tumors were reclassified according to the predominant histologic subtype, and comprehensive histologic subtyping with semiquantitative assessment of each of the histologic subtypes in increments of 5% was performed. Correlations with epidermal growth factor receptor status were then evaluated. RESULTS: Epidermal growth factor receptor mutations were found in 54 cases (50.5%). Epidermal growth factor receptor mutations were significantly associated with the micropapillary predominant subtype (P = .02) and with the presence (any amount) of the lepidic component (P = .02). CONCLUSION: The upcoming International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of lung adenocarcinoma is relevant in that it shows a phenotype genotype correlation. Comprehensive histologic subtyping should be recommended because of the association of particular subtypes with epidermal growth factor receptor mutations. PMID- 21970489 TI - Sudan black B reduces autofluorescence in murine renal tissue. AB - CONTEXT: Renal tissue emits intense autofluorescence, making it difficult to differentiate specific immunofluorescence signals and thus limiting its application to clinical biopsy material. OBJECTIVE: To identify and minimize autofluorescence of renal tissue and demonstrate a simple, efficient method to reduce autofluorescence using Sudan black B. DESIGN: In this study, the sources and features of autofluorescence emitted from kidney tissue were examined. Broad autofluorescence was visualized in both frozen and paraffin kidney sections of normal mice and mice with Adriamycin-induced nephropathy using confocal laser scanning microscopy. Autofluorescence appeared in commonly used 4',6-diamidino-2 phenylindole, fluorescein isothiocyanate, and Texas Red channels but not in far red channel, and emitted extensively from red cells, injured tubulointersitial cells, and protein casts in diseased kidney. To eliminate autofluorescence, Sudan black B was used on formaldehyde-fixed paraffin sections and frozen sections of mouse kidney. The effects of Sudan black B in various concentrations were tested on kidney tissue. RESULTS: The 0.1% Sudan black B effectively blocked autofluorescence from both paraffin and frozen sections without adversely affecting specific fluorescence signals. Interestingly, the solvent for Sudan black B, 70% ethanol, was also shown to reduce autofluorescence on frozen sections, but not on paraffin sections. CONCLUSIONS: This study demonstrates a simple, efficient, and cost-effective method to reduce autofluorescence using Sudan black B, and also provides a comprehensive approach to identify and minimize autofluorescence of renal tissue. PMID- 21970490 TI - Confocal laser endomicroscopy: a primer for pathologists. AB - CONTEXT: The advent of new endoscopic optical techniques is likely to change pathologists' role in diagnosis. OBJECTIVE: To describe how confocal laser endomicroscopy (CLE) works, show its advantages and limitations compared to cytohistologic biopsy, and explore how it may affect the practice of pathology. DATA SOURCES: Literature review. CONCLUSIONS: Confocal laser endomicroscopy is proving its ability to provide histology-like images of tissues in vivo to help avoid risks and costs of conventional biopsies. Confocal imaging restricts light to 1 plane, emulating a paraffin section, and topical or systemic optical contrast agents allow subcellular resolution. New contrast agents could theoretically permit molecular characterization. In vivo imaging has begun to demonstrate novel, dynamic types of diagnostic features. Decreased histologic biopsies can be anticipated for a few scenarios. Significant limitations of CLE include the inability to create a tissue archive for broad molecular classification, suboptimal contrast agents, small fields of view and shallow penetration, paucity of clinical validation studies, and problems with reimbursement. Confocal laser endomicroscopy exposes new opportunities for pathologists: CLE technologies can be exploited in pathology, and diagnostic criteria expanded based on endoscopists' discoveries. Potential synergy exists between CLE and cytology, allowing the low-magnification diagnostic architectural changes by CLE and cytomorphology to emulate the full diagnostic information in a histologic biopsy while providing an archive of material for molecular or immunohistochemical studies. Confocal laser endomicroscopy will decrease some types of biopsies, but offers an opportunity for pathologists to find new ways to provide value and improve patient care. PMID- 21970491 TI - United States Medical Licensing Examination step 1 two-digit score: a correlation with the American Board of Pathology first-time test taker pass/fail rate at the University of Pittsburgh Medical Center. AB - CONTEXT: Factors that correlate with success or failure on the American Board of Pathology (ABP) examination are not known. Other medical residency programs have shown that standardized test scores correlate with specialty board examination scores; however, data from pathology programs are lacking. OBJECTIVE: To investigate whether the 2-digit score on step 1 of the United States Medical Licensing Examination (USMLE) was correlated with ABP examination performance at a large university pathology program. DESIGN: Nine years of data (2001-2009) from pathology residents (n = 72) at the University of Pittsburgh Medical Center (UPMC, Pittsburgh, Pennsylvania) was collected from existing files and deidentified. Step 1 USMLE 2-digit scores and ABP failure rates for first-time test takers were compared. Results are reported as the percentage of residents who failed either the anatomic pathology or clinical pathology part of the ABP examination in cohorts by their USMLE 2-digit score (<=80, 81-85, 86-89, >=90). RESULTS: The rolling 5-year (2005-2009) ABP average failure rate for first-time test takers of the anatomic pathology examination was 3.1% (UPMC) and 14.1% (nationally); in clinical pathology, it was 13.8% (UPMC) and 23.6% (nationally). At UPMC, no resident failed the anatomic pathology or clinical pathology parts of the ABP examination if his or her 2-digit USMLE step 1 score was 90 or more across 9 years of training (2001-2009). CONCLUSIONS: In the UPMC pathology program, 2-digit scores on USMLE step 1 of 90 or more and 80 or less were strong measures of ABP first-time pass/failure rates, whereas scores of 81 to 89 were less-accurate measures. The USMLE step 1 score is one of many criteria that can be used for screening applicants for a pathology residency program. PMID- 21970492 TI - Pleomorphic (spindle and squamous cell) carcinoma arising in a peripheral mixed squamous and glandular papilloma in a 70-year-old man. AB - Solitary papillomas of the bronchial tree are rare, particularly in the distal airways. When encountered, solitary papillomas are not frequently found to undergo malignant transformation. When this does happen, it is usually a squamous cell carcinoma arising in a human papillomavirus-associated squamous papilloma (usually in a central airway). Here we report a unique case of pleomorphic (spindle and squamous cell) carcinoma arising in a mixed glandular and squamous papilloma without human papillomavirus association. PMID- 21970493 TI - Cutaneous infections caused by Herpesviridae: a review. AB - The herpes family of viruses accounts for a significant proportion of human cutaneous disease. Although most episodes of viral infection can be diagnosed clinically, a small subset of these outbreaks will require biopsy for histologic interpretation and diagnosis. Most herpesviruses cause characteristic architectural and cytologic changes in the context of active infection, whereas the effects of some will not manifest until the future as malignant disease. Other infections may go unnoticed secondary to a lack of specific histologic findings. Because herpesviruses cause such a wide spectrum of cutaneous conditions, it is prudent that pathologists be aware of the varied clinical and histopathologic presentations so that these infections will not persist undiagnosed. Additionally, methods of virus detection will briefly be reviewed. PMID- 21970494 TI - Primary diffuse large B-cell lymphoma of the testis. AB - In this short review, we discuss primary diffuse large B-cell lymphoma of the testis, an entity that is most commonly seen in older patients. The most common clinical presentation is a unilateral testicular mass. Microscopically, the tumor shows diffuse infiltration of lymphocytes between intact seminiferous tubules. Spermatogenic arrest, interstitial fibrosis, and tubular hyalinization are commonly seen. The tumor is positive for B-cell markers by immunohistochemistry. Treatment has traditionally been with orchiectomy and combination chemotherapy; however, only a minority of patients enjoy a prolonged disease-free survival. Differential diagnosis includes seminoma and viral and granulomatous orchitis. PMID- 21970496 TI - Modulation of inflammatory responses by a cannabinoid-2-selective agonist after spinal cord injury. AB - The goal of the current investigation was to evaluate the mechanisms through which administration of a selective cannabinoid-2 (CB2) agonist (O-1966) modifies inflammatory responses and helps to improve function following spinal cord injury. A comparison of motor function, autonomic function, and inflammatory responses was made between animals treated with O-1966 (5 mg/kg IP) and animals treated with vehicle 1 h and 24 h following contusion injury to the spinal cord. Motor function was significantly improved in the treated animals at each time point during the 14 days of evaluation. The percentage of animals able to spontaneously void their bladder was also greater over the entire study period in the group treated with the selective CB2 agonist. Seven days following injury there was a significant reduction in both hematopoietic and myeloid cell invasion of the spinal cord, and a reduction in the number of immunoreactive microglia. The results of the evaluation of chemokine/cytokine expression and inflammatory cell invasion also demonstrated a significant effect of treatment on inflammatory reactions following injury. Two days after injury, animals treated with O-1966 had significant reductions in CXCL-9 and CXCL-11, and dramatic reductions in IL 23p19 expression and its receptor IL-23r. Treatment with O-1966 also caused inhibition of toll-like receptor expression (TLR1, TLR4, TLR6 and TLR7) following injury. These results demonstrate that the improvement in motor and autonomic function resulting from treatment with a selective CB2 agonist is associated with a significant effect on inflammatory responses in the spinal cord following injury. PMID- 21970497 TI - Interaction between resveratrol and thrombin and its biological implication. AB - In view of important implication of resveratrol and thrombin in the process of platelet aggregation and apoptosis, the interaction effect between them and its biological implication was studied. Resveratrol could decrease fluorescence emission intensities of thrombin by a dynamic collision quenching process. The binding process was spontaneous and the resveratrol-thrombin complex formation was an endothermal reaction induced by hydrophobic interaction and hydrogen. Non radiation energy transfer occurred from thrombin to resveratrol at the molecular level. Kinetic studies showed that the fluorescence intensity of thrombin linearly decreased along with prolonged time, whereas resveratrol intensity reduced continuously with degressive plateau in the form of second exponential decay function. Moreover, the interaction caused a decrease of alpha-helical structure resulting in thrombin conformation alteration. In addition, the isomerization of resveratrol was not prevented but its stability was improved with the addition of thrombin. This work might give deeper insight into resveratrol as a kind of nutritional factor with the inhibition of platelet aggregation and stimulation of platelet apoptosis in the functional food. PMID- 21970505 TI - Evaluation of hepatic iron overload in Chinese children with beta-thalassemia major. AB - Patients with beta-thalassemia major require long-term blood transfusions, resulting in hepatic iron overload. Thirty-five Chinese children with beta thalassemia major were recruited in the present studies. Hepatic iron overload was evaluated by histological grading. The relationships between hepatic iron overload and both serum biochemical markers and magnetic resonance imaging (MRI) examination were studied. The majority of the patients showed high degrees of hepatic iron overload by histological study. The degree of hepatic iron overload was correlated with serum ferritin (r = .70, P < .01), hyaluronic acid (r = .58, P = .011), and type III precollagen (r = .55, P = .035). Moreover, hepatic iron overload showed a negative correlation with liver to muscle signal intensity ratio (r = -.44, P = .012), and a positive correlation with red marrow area percentage (r = .52, P < .01). These results indicated that hepatic iron overload might be assessed by serum biochemical markers and MRI examination. PMID- 21970506 TI - Secondary hemophagocytosis in 3 patients with organic acidemia involving propionate metabolism. AB - Hemophagocytic lymphohistiocytosis (HLH) may develop secondary to infections, malignancies, immune deficiency syndromes, and rheumatologic and metabolic disorders. Associations between HLH and inborn errors of metabolism, including lysinuric protein intolerance, multiple sulfatase deficiency, galactosemia, Gaucher disease, Pearson syndrome, and galactosialidosis, have previously been reported in the literature. In this report the authors present 3 children with disorders of propionate metabolism--1 with methylmalonic acidemia and 2 with propionic acidemia--who developed secondary HLH during their metabolic attacks. All patients fulfilled the 5 HLH criteria of the Histiocyte Society. Familial HLH was ruled out by molecular analysis. Plasma exchange was performed for 2 of them. Unfortunately 1 died of multiorgan failure despite intensive therapy. This is the first report of such an association. PMID- 21970507 TI - Management of severe refractory thrombocytopenia in dengue hemorrhagic fever with intravenous anti-D immune globulin. AB - Dengue hemorrhagic fever (DHF) is a potentially lethal complication of dengue fever due to shock and/or bleeding. Bleeding in DHF is due to thrombocytopenia and/or coagulopathy. The authors present their experience of usage of intravenous anti-D in 5 children with DHF and severe refractory thrombocytopenia (<10,000/mm(3)). It was administered in a dose of 50 to 75 MUg/kg. Mean platelet count was 6800/mm(3) before and 33,600, 44,600, and 79,000/mm(3) after intravenous anti-D administration at 24, 48, and 72 hours, respectively. Average drop in hemoglobin after administration of anti-D was 2.28 g/dL. Intravenous anti D can possibly be a treatment option for refractory thrombocytopenia in DHF. PMID- 21970508 TI - The effect of menopause on the skin and other connective tissues. AB - Cutaneous ageing manifests itself as a progressive reduction in function and reserve capacity of skin tissue. Collagen atrophy is a major factor in skin ageing. There is a strong correlation between skin collagen loss and oestrogen deficiency due to the menopause. Skin ageing is associated with a progressive increase in extensibility and a reduction in elasticity. With increasing age, the skin also becomes more fragile and susceptible to trauma, leading to more lacerations and bruising. Furthermore, wound healing is impaired in older women. Oestrogen use after the menopause increases collagen content, dermal thickness and elasticity, and it decreases the likelihood of senile dry skin. Large-scale clinical trials are necessary to help make informed recommendations regarding postmenopausal oestrogen use and its role in the prevention of skin ageing. Oestrogen has profound effects on connective tissue turnover, no matter the site. It has been shown that menopause has similar effects on the connective tissue of the carotid artery media, intervertebral discs and bones. PMID- 21970509 TI - Bridging consent: from toll bridges to lift bridges? AB - BACKGROUND: The ability to share human biological samples, associated data and results across disease-specific and population-based human research biobanks is becoming increasingly important for research into disease development and translation. Although informed consent often does not anticipate such cross domain sharing, it is important to examine its plausibility. The purpose of this study was to explore the feasibility of bridging consent between disease-specific and population-based research. Comparative analyses of 1) current ethical and legal frameworks governing consent and 2) informed consent models found in disease-specific and population-based research were conducted. DISCUSSION: Ethical and legal frameworks governing consent dissuade cross-domain data sharing. Paradoxically, analysis of consent models for disease-specific and population-based research reveals such a high degree of similarity that bridging consent could be possible if additional information regarding bridging was incorporated into consent forms. We submit that bridging of consent could be supported if current trends endorsing a new interpretation of consent are adopted. To illustrate this we sketch potential bridging consent scenarios. SUMMARY: A bridging consent, respectful of the spirit of initial consent, is feasible and would require only small changes to the content of consents currently being used. Under a bridging consent approach, the initial data and samples collection can serve an identified research project as well as contribute to the creation of a resource for a range of other projects. PMID- 21970510 TI - Direct-writing of PbS nanoparticles inside transparent porous silica monoliths using pulsed femtosecond laser irradiation. AB - Pulsed femtosecond laser irradiation at low repetition rate, without any annealing, has been used to localize the growth of PbS nanoparticles, for the first time, inside a transparent porous silica matrix prepared by a sol-gel route. Before the irradiation, the porous silica host has been soaked within a solution containing PbS precursors. The effect of the incident laser power on the particle size was studied. X-ray diffraction was used to identify the PbS crystallites inside the irradiated areas and to estimate the average particle size. The localized laser irradiation led to PbS crystallite size ranging between 4 and 8 nm, depending on the incident femtosecond laser power. The optical properties of the obtained PbS-silica nanocomposites have been investigated using absorption and photoluminescence spectroscopies. Finally, the stability of PbS nanoparticles embedded inside the host matrices has been followed as a function of time, and it has been shown that this stability depends on the nanoparticle mean size. PMID- 21970511 TI - A cluster-randomized controlled trial to reduce sedentary behavior and promote physical activity and health of 8-9 year olds: the Transform-Us! study. AB - BACKGROUND: Physical activity (PA) is associated with positive cardio-metabolic health and emerging evidence suggests sedentary behavior (SB) may be detrimental to children's health independent of PA. The primary aim of the Transform-Us! study is to determine whether an 18-month, behavioral and environmental intervention in the school and family settings results in higher levels of PA and lower rates of SB among 8-9 year old children compared with usual practice (post intervention and 12-months follow-up). The secondary aims are to determine the independent and combined effects of PA and SB on children's cardio-metabolic health risk factors; identify the factors that mediate the success of the intervention; and determine whether the intervention is cost-effective. METHODS/DESIGN: A four-arm cluster-randomized controlled trial (RCT) with a 2 * 2 factorial design, with schools as the unit of randomization. Twenty schools will be allocated to one of four intervention groups, sedentary behavior (SB-I), physical activity (PA-I), combined SB and PA (SB+PA-I) or current practice control (C), which will be evaluated among approximately 600 children aged 8-9 years in school year 3 living in Melbourne, Australia. All children in year 3 at intervention schools in 2010 (8-9 years) will receive the intervention over an 18 month period with a maintenance 'booster' delivered in 2012 and children at all schools will be invited to participate in the evaluation assessments. To maximize the sample and to capture new students arriving at intervention and control schools, recruitment will be on-going up to the post-intervention time point. Primary outcomes are time spent sitting and in PA assessed via accelerometers and inclinometers and survey. DISCUSSION: To our knowledge, Transform-Us! is the first RCT to examine the effectiveness of intervention strategies for reducing children's overall sedentary time, promoting PA and optimizing health outcomes. The integration of consistent strategies and messages to children from teachers and parents in both school and family settings is a critical component of this study, and if shown to be effective, may have a significant impact on educational policies as well as on pedagogical and parenting practices. TRIAL REGISTRATION: ACTRN12609000715279; Current Controlled Trials ISRCTN83725066. PMID- 21970513 TI - Cell delivery systems using alginate--carrageenan hydrogel beads and fibers for regenerative medicine applications. AB - The present work was focused on the development and characterization of new hydrogel systems based on natural origin polymers, namely, alginate and carrageenan, into different formats and with adequate properties to sustain the viability of encapsulated cells, envisioning their application as cell delivery vehicles for tissue regeneration. Different formulations of alginate and carrageenan hydrogels and different processing parameters were considered to determine the best conditions required to achieve the most adequate response in terms of the mechanical stability, cell viability, and functionality of the developed systems. The morphology, size, and structure of the hydrogels and their degradation behavior and mechanical properties were evaluated during this study. In addition to cytotoxicity studies, preliminary experiments were carried out to investigate the ability of alginate--carrageenan beads/fibers to encapsulate chondrocytes. The results obtained indicated that the different formulations, both in the form of beads and fibers, have considerable potential as cell-carrier materials for cell delivery in tissue engineering/regenerative medicine applications. PMID- 21970512 TI - Red blood cell transfusion in the critically ill patient. AB - Red blood cell (RBC) transfusion is a common intervention in intensive care unit (ICU) patients. Anemia is frequent in this population and is associated with poor outcomes, especially in patients with ischemic heart disease. Although blood transfusions are generally given to improve tissue oxygenation, they do not systematically increase oxygen consumption and effects on oxygen delivery are not always very impressive. Blood transfusion may be lifesaving in some circumstances, but many studies have reported increased morbidity and mortality in transfused patients. This review focuses on some important aspects of RBC transfusion in the ICU, including physiologic considerations, a brief description of serious infectious and noninfectious hazards of transfusion, and the effects of RBC storage lesions. Emphasis is placed on the importance of personalizing blood transfusion according to physiological endpoints rather than arbitrary thresholds. PMID- 21970515 TI - Graphene bimetallic-like cantilevers: probing graphene/substrate interactions. AB - The remarkable mechanical properties of graphene, the thinnest, lightest, and strongest material in existence, are desirable in applications ranging from composite materials to sensors and actuators. Here, we demonstrate that these mechanical properties are strongly affected by the interaction with the substrate onto which graphene is deposited. By measuring the temperature-dependent deflection of graphene/substrate "bimetallic" cantilevers we determine strain, thermal expansion coefficient, and the adhesion force acting on graphene films attached to a substrate. Graphene deposited on silicon nitride (SiN(x)) is under much larger strain, epsilon(g) ~ 1.5 * 10(-2), compared to graphene on gold (Au), epsilon(g) < 10(-3). The thermal expansion coefficient alpha(g) of graphene attached to SiN(x) is found to be negative, in the range from (- 5... - 1) * 10( 6)K(-1) and smaller in magnitude than alpha(g) of suspended graphene. We also estimate the interfacial shear strength of the graphene/SiN(x) interface to be ~1 GPa at room temperature. PMID- 21970516 TI - Detection of clusters of a rare disease over a large territory: performance of cluster detection methods. AB - BACKGROUND: For many years, the detection of clusters has been of great public health interest. Several detection methods have been developed, the most famous of which is the circular scan method. The present study, which was conducted in the context of a rare disease distributed over a large territory (7675 cases registered over 17 years and located in 1895 units), aimed to evaluate the performance of several of the methods in realistic hot-spot cluster situations. METHODS: All the methods considered aim to identify the most likely cluster area, i.e. the zone that maximizes the likelihood ratio function, among a set of cluster candidates. The circular and elliptic scan methods were developed to detect regularly shaped clusters. Four other methods that focus on irregularly shaped clusters were also considered (the flexible scan method, the genetic algorithm method, and the double connected and maximum linkage spatial scan methods). The power of the methods was evaluated via Monte Carlo simulations under 27 alternative scenarios that corresponded to three cluster population sizes (20, 45 and 115 expected cases), three cluster shapes (linear, U-shaped and compact) and three relative risk values (1.5, 2.0 and 3.0). RESULTS: Three situations emerged from this power study. All the methods failed to detect the smallest clusters with a relative risk lower than 3.0. The power to detect the largest cluster with relative risk of 1.5 was markedly better for all methods, but, at most, half of the true cluster was captured. For other clusters, either large or with the highest relative risk, the standard elliptic scan method appeared to be the best method to detect linear clusters, while the flexible scan method localized the U-shaped clusters more precisely than other methods. Large compact clusters were detected well by all methods, with better results for the circular and elliptic scan methods. CONCLUSIONS: The elliptic scan method and flexible scan method seemed the most able to detect clusters of a rare disease in a large territory. However, the probability of detecting small clusters with relative risk lower than 3.0 remained low with all the methods tested. PMID- 21970517 TI - Cross-linking mechanisms of arginine and lysine with alpha,beta-dicarbonyl compounds in aqueous solution. AB - Cross-linking in proteins by alpha,beta-dicarbonyl compounds is one of the most damaging consequences of reactive carbonyl species in vivo and in foodstuffs. In this article we investigate computationally the cross-linking of glyoxal and methylglyoxal with lysine and arginine residues using density functional theory and the wB97XD dispersion-corrected functional. Five pathways, A-E, have been characterized. In pathways A and B, the reaction proceeds via formation of the Schiff base, aldimine, followed by addition of arginine. In contrast, in pathways C-E, direct addition of arginine to the dicarbonyl compounds occurs first, leading to a dihydroxyimidazolidine intermediate, which then reacts with lysine after dehydration and proton transfer reactions. The results reveal that pathways A, C, and E are competitive whereas reactions via pathways B and D are much less favorable. Inclusion of up to five explicit water molecules in the proton transfer and dehydration steps is found to lower the energy barriers in the feasible pathways by about 5-20 kcal/mol. Comparison of the mechanisms of methylglyoxal-derived imidazolium cross-linking (MODIC) and glyoxal-derived imidazolium cross-linking (GODIC) shows that the activation barriers are lower for GODIC than MODIC, in agreement with experimental observations. PMID- 21970518 TI - Tuning the optical and electronic properties of 4,8-disubstituted benzobisoxazoles via alkyne substitution. AB - In an effort to design new electron-deficient building blocks for the synthesis of conjugated materials, a series of new trans-benzobisoxazoles bearing halogen or alkynyl substituents at the 4,8-positions was synthesized. Additionally, the impact of these modifications on the optical and electronic properties was investigated. Theoretical calculations predicted that the incorporation of various alkynes can be used to tune the energy levels and band gaps of these small molecules. The targeted 4,8-disubstituted benzobisoxazoles were easily prepared in good yields using a two-step reaction sequence: Lewis acid catalyzed orthoester cyclization followed by Sonogashira cross-coupling. The experimentally determined HOMO values for these 4,8-disubstituted benzobisoxazoles ranged from 4.97 to -6.20 eV and showed reasonable correlation to the theoretically predicted values, with a percent deviation that ranged from 2.4-12.8%. However, the deviation between actual and predicted HOMO values was reduced to less than 3.5% when the theoretical values were extrapolated to the long-chain limit and compared to copolymers containing the 4,8-disubstituted benzobisoxazoles. Collectively, these results indicate that these 4,8-disubstituted trans benzobisoxazoles can be used for the synthesis of new conjugated materials with electronic properties that are variable and predictable. PMID- 21970519 TI - Evaluation of epithelial mesenchymal transition in patients with chronic obstructive pulmonary disease. AB - BACKGROUND: The reticular basement membrane (Rbm) in smokers and especially smokers with COPD is fragmented with "clefts" containing cells staining for the collagenase matrix-metalloproteinase-9 (MMP-9) and fibroblast protein, S100A4. These cells are also present in the basal epithelium. Such changes are likely hallmarks of epithelial mesenchymal transition (EMT). We aimed to confirm the epithelial origin of these Rbm cells, and to exclude potential confounding by infiltrating inflammatory cells. METHODS: Endobronchial biopsy sections from 17 COPD current smokers, with documented Rbm splitting and cellularity were stained for neutrophil elastase (neutrophil marker), CD68 (macrophage/mature fibroblasts), CD4+/CD8+ T lymphocytes, CD19 (B-cells), CD11c (dendritic cells/inflammatory cells), and S100 (Langerhans cells). The number of cells in the Rbm and epithelium staining for these "inflammatory" cell markers were then compared to numbers staining for S100A4, "a documented EMT epitope". Slides were double stained for S100A4 and cytokeratin(s). RESULTS: In the basal epithelium significantly more cells stained for S100A4 compared to infiltrating macrophages, fibroblasts or immune cells: median, 26 (21.3 - 37.3) versus 0 (0 - 9.6) per mm, p < 0.003. Markedly more S100A4 staining cells were also observed in the Rbm compared to infiltrating macrophages, neutrophils, fibroblasts or immune cells or any sub-type: 58 (37.3 - 92.6) versus 0 (0 - 4.8) cells/mm Rbm, p < 0.003. Cells in the basal epithelium 26 (21.3 - 37.3) per mm) and Rbm (5.9 (2.3 - 13.8) per mm) frequently double stained for both cytokeratin and S100A4. CONCLUSIONS: These data provide additional support for active EMT in COPD airways. PMID- 21970520 TI - Development of a short form of Mini-Mental State Examination for the screening of dementia in older adults with a memory complaint: a case control study. AB - BACKGROUND: Primary care physicians need a brief and accurate screening test of dementia. The objective of this study was to determine whether a short form of Mini-Mental State Examination (SMMSE) was as accurate as the Mini-Mental State Examination (MMSE) in screening dementia. METHODS: Based on case control design study, SMMSE and MMSE were assessed in 184 community-dwelling older adults (mean age 81.3 +/- 6.5 years, 71.7% women) with memory complaint sent by their primary care physician to a memory clinic. Included participants were separated into two groups: cognitively healthy individuals and demented individuals. RESULTS: The trade-off between sensitivity and specificity of the SMMSE for clinically diagnosed dementia was 4. Based on the cut-off value <= 4 for SMMSE and a cut-off value <= 24 for MMSE, the sensitivity of both tests was similar (89.5% for SMMSE versus 90.0% for MMSE), whereas the specificity, the positive predictive values (PPV) and the negative predictive values (NPV) were higher for SMMSE compared to MMSE (85.4 versus 75.5% for specificity; 95.5% versus 92.8% for PPV; 70.0 versus 68.9 for NPV). The positive and negative Likehood Ratio (LR) of SMMSE were higher than those of MMSE (respectively, 6.1 versus 3.7; 8.1 versus 7.7). In addition, odds ratio (OR) for dementia was higher for the SMMSE compared to the MMSE (OR = 49.8 with 95% confident interval (CI) [18.0; 137.8] versus OR = 28.6 with 95% CI [11.6; 70.3]). CONCLUSIONS: SMMSE seems to be an efficient short screening test for dementia among community-dwelling older adults with a memory complaint. Further research is needed to confirm its predictive values among unselected primary care older patients. PMID- 21970521 TI - Phalangeal densitometry compared with dual energy X-ray absorptiometry for assessment of bone mineral density in elderly women. AB - BACKGROUND: Reduced bone mineral density (BMD) is identified as a major risk factor for fracture. The World Health Organization criterion for diagnosis of osteoporosis (T-score <=-2.5 SD) is based on dual energy X-ray absorptiometry (DXA) measurements. However DXA availability may be limited in some regions. In this study the ability of the phalangeal radiographic absorptiometry (RA) device, MetriScan, to identify women with reduced BMD at the femoral neck assessed by DXA was evaluated. METHODS: The study population contained women with recent low energy distal radius fracture and women recruited from the general population, all aged >=50 years. A triage approach was applied in which two cut-offs for RA T score were defined at which individuals with 90% sensitivity and 90% specificity could be identified to have or not have reduced BMD at the femoral neck defined as T-score <=-2.5 SD. RESULTS: The correlation between phalangeal RA BMD and femoral neck DXA BMD was r=0.65 (p<0.001). The upper and lower RA T-score cut-off was -1.5 SD and -2.9 SD. With the triage approach being used for the whole cohort, 34% would require a central DXA assessment to determine if the femoral neck T-score is below or above -2.5 SD. CONCLUSION: The application of the RA MetriScan device can reduce the number of DXA assessments needed to detect reduced BMD. The device may thus be of clinical value if access to DXA is limited, as well as for screening purposes. PMID- 21970522 TI - Cardiorespiratory fitness, adiposity, and serum 25-dihydroxyvitamin D levels in women: the Cooper Center Longitudinal Study. AB - PURPOSE: We examined the cross-sectional associations among cardiorespiratory fitness (CRF), different measures of adiposity, and serum vitamin D levels in women. METHODS: Between 2007 and 2010, 1320 women completed a health examination. Measures included body mass index (BMI), waist circumference (WC), waist/hip ratio, percent body fat, CRF based on a maximal treadmill exercise test, and measurement of serum vitamin D. Participants were classified by CRF as unfit (lowest 20%) and fit (remaining 80%) based on age, as well as by clinical cutoff points for adiposity measures, and by categories of serum vitamin D. We examined trends of CRF and adiposity exposures across serum vitamin D categories. We calculated odds ratios (OR) of serum vitamin D insufficiency or deficiency across levels of adiposity exposures before and after adjustment for CRF. RESULTS: We observed a significant positive trend for CRF across incremental serum vitamin D categories (p<0.001). When compared to ORs for normal weight women, ORs for serum vitamin D insufficiency or deficiency were significantly higher for overweight women within each adiposity exposure (p<0.05). When grouped into categories of fit and unfit (upper 80% and lower 20% of CRF distribution, respectively), serum vitamin D was significantly lower in unfit than in fit women within each stratum of WC and waist/hip ratio and within the normal weight BMI stratum. CONCLUSIONS: Serum vitamin D levels are positively associated with CRF and negatively associated with different measures of adiposity in women. Higher CRF attenuates the relationship between adiposity level and serum vitamin D. Future prospective studies are warranted. PMID- 21970523 TI - Electrochemical determination of dopamine based on self-assembled peptide nanostructure. AB - Self-assembled peptide nanostructures are electronically insulating as are most biomaterials derived from natural amino acids. To obtain additional properties and increase the applicability of peptide nanomaterials, some chemical modifications can be performed and materials can be functionalized to form hybrid compounds. In this work, we described the formation of L-diphenylalanine nanotubes (PNTs) with cyclic-tetrameric copper(II) species containing the ligand (4-imidazolyl)ethylene-2-amino-1-ethylpyridine [Cu(4)(apyhist)(4)](4+) in the Nafion membrane on a vitreous carbon electrode surface. This copper complex has been studied as structural and functional models for the active centers of copper containing redox enzymes. Scanning electron microscopy was used to confirm the formation of the nanostructures. The electrochemical properties of the PNT [Cu(4)(apyhist)(4)](4+)/Nafion film on a glassy carbon electrode were characterized using cyclic voltammetry and square-wave voltammetry and showed high electrocatalytic activity toward the oxidation of dopamine (DA). The detection sensitivity was found to be enhanced by the use of copper(II) complex in the PNTs/Nafion films. Under the optimum conditions, the square-wave voltammetry peak height was linearly related to the DA concentration over two concentration intervals, viz., 5.0-40 MUmol L(-1) and 40-1000 MUmol L(-1). The detection limit was 2.80 MUmol L(-1) (S/N = 3), and ascorbic acid did not interfere with the DA detection. These results suggested that this hybrid bioinorganic system provides an attractive advantage for a new type of electrochemical sensors. The detection sensitivity was found to be enhanced by use of PNTs. PMID- 21970524 TI - Photogenerated defects in shape-controlled TiO2 anatase nanocrystals: a probe to evaluate the role of crystal facets in photocatalytic processes. AB - The promising properties of anatase TiO(2) nanocrystals exposing specific surfaces have been investigated in depth both theoretically and experimentally. However, a clear assessment of the role of the crystal faces in photocatalytic processes is still under debate. In order to clarify this issue, we have comprehensively explored the properties of the photogenerated defects and in particular their dependence on the exposed crystal faces in shape-controlled anatase. Nanocrystals were synthesized by solvothermal reaction of titanium butoxide in the presence of oleic acid and oleylamine as morphology-directing agents, and their photocatalytic performances were evaluated in the phenol mineralization in aqueous media, using O(2) as the oxidizing agent. The charge trapping centers, Ti(3+), O(-), and O(2)(-), formed by UV irradiation of the catalyst were detected by electron spin resonance, and their abundance and reactivity were related to the exposed crystal faces and to the photoefficiency of the nanocrystals. In vacuum conditions, the concentration of trapped holes (O( ) centers) increases with increasing {001} surface area and photoactivity, while the amount of Ti(3+) centers increases with the specific surface area of {101} facets, and the highest value occurs for the sample with the worst photooxidative efficacy. These results suggest that {001} surfaces can be considered essentially as oxidation sites with a key role in the photoxidation, while {101} surfaces provide reductive sites which do not directly assist the oxidative processes. Photoexcitation experiments in O(2) atmosphere led to the formation of Ti(4+) O(2)(-) oxidant species mainly located on {101} faces, confirming the indirect contribution of these surfaces to the photooxidative processes. Although this work focuses on the properties of TiO(2), we expect that the presented quantitative investigation may provide a new methodological tool for a more effective evaluation of the role of metal oxide crystal faces in photocatalytic processes. PMID- 21970525 TI - De novo malignant solitary fibrous tumor of the kidney. AB - The kidney is a relatively infrequent site for solitary fibrous tumor (SFT). Among the previously reported cases, only two cases of malignant renal SFT developing via dedifferentiation from a pre-existing benign SFT have been reported. Here we reported a case of de novo malignant renal SFT clinically diagnosed as renal cell carcinoma in a 50-year-old woman. The tumor was circumscribed but unencapsulated and showed obvious hemorrhagic necrosis. Microscopically, the tumor was composed of patternless sheets of alternating hypercellular and hypocellular areas of spindle cells displaying mild to moderate nuclear atypia, frequent mitoses up to 8 per 10 high power fields, and a 20% Ki 67 proliferative index. Immunohistochemical studies revealed reactivity for CD34, CD99 and vimentin, with no staining for all other markers, confirming the diagnosis of SFT. No areas of dedifferentiation were seen after extensive sampling. Based on the pathologic and immunohistochemical features, a diagnosis of de novo malignant renal SFT was warranted. Our report expands the spectrum of malignant progression in renal SFTs. Even though this patient has been disease free for 30 months, long-term follow-up is still mandatory. PMID- 21970526 TI - Individual differences in the impact of attentional bias training on cardiovascular responses to stress in women. AB - Experimental studies show that training people to attend to negative stimuli makes them more likely to respond with greater anxiety to stress. The present study investigated this effect in students using measures of cardiovascular responses to stress and examined whether individual differences influence the impact of attention training on stress responses. Using a standard dot probe task, 30 participants underwent negative attentional bias training and 34 participants underwent anti-negative training before completing a stressful speech task. Results indicated that, overall, participants exhibited acclimatization to the procedures (indicated by a dip in blood pressure post training) and normal stress responding (indicated by elevated blood pressure in response to stress; p<.001). However, consideration of participants' scores for neuroticism/emotional-stability revealed important differences in how the intervention impacted on cardiovascular profiles (p=.008). For participants with high neuroticism scores, the negative attentional bias intervention elicited more exaggerated stress responding than the anti-negative intervention. For those with low neuroticism scores (i.e., emotionally stable participants), the anti-negative intervention was associated with elevated post-intervention blood pressure and higher blood pressure reactivity to stress. These findings provide evidence of the impact of attentional bias manipulation on physiological stress reactivity and suggest the effect is highly contingent on individual temperaments. PMID- 21970527 TI - Probiotic upregulation of peripheral IL-17 responses does not exacerbate neurological symptoms in experimental autoimmune encephalomyelitis mouse models. AB - CONTEXT: It is of great importance to evaluate the safety of probiotics in dysregulated immune conditions, as probiotics can possibly modulate immune functions in the host. OBJECTIVE: We tried to confirm the safety of using Lactobacillus casei strain Shirota (LcS) to help prevent autoimmunity in the central nervous system. METHODS: We used two chronic experimental autoimmune encephalomyelitis (EAE) models, a relapse and remission type EAE model in SJL/J mice and a durable type model in C57BL/6 mice. LcS was administered from 1 week before antigen sensitization until the end of the experiments, and neurological symptoms and histopathological changes of the spinal cord were observed. Immunological parameters were also examined in the SJL/J mouse model. RESULTS: LcS administration did not exacerbate neurological symptoms or histopathological changes of the spinal cord in either model but instead tended to improve neurological symptoms in the SJL/J mouse EAE model. LcS administration transiently upregulated IL-17 production by antigen-stimulated lymphocytes of draining lymph nodes 7 days after sensitization. Enhanced production of IL-10 and an increase in the percentage of CD4(+)CD25(+) T regulatory cells were also observed at the same sites. Strong expression of IL-17 mRNA was detected in the spinal cord of mice that displayed severe neurological symptoms on day 12, but this expression was not enhanced by LcS administration. CONCLUSION: These results demonstrate that LcS does not exacerbate, but instead may improve EAE depending on the immunization conditions, and that IL-17 responses at peripheral sites may not always result in a worsening of autoimmune diseases. PMID- 21970528 TI - Photomedicine and LLLT literature watch. PMID- 21970540 TI - The 2,11-cyclized cembranoids: cladiellins, asbestinins, and briarellins (period 1998-2010). AB - The 2,11-cyclized cembranoids are isolated from marine invertebrates of Octocorallia species. They are a very interesting class of natural products sharing a common oxatricyclo[6.6.1.0(2,7)]pentadecane core and carrying a varied substituent pattern. This review presents their structural diversity along with the reported biological activities. The 2,11-cyclized cembranoids were comprehensively reviewed previously in 1998, and this contribution will serve as an update of that work. Since 1998 a number of structural assignments of the isolated products have been revised, some as a result of total synthesis efforts. The chemical reactivity of several of the natural compounds has been studied, and the relevance of these findings to the biosynthesis or the generation of isolation artifacts is discussed. The wide range of biological activities displayed by the 2,11-cyclized cembranoids justifies the interest shown within the synthetic chemistry community and suggests that this class of natural products remains a fruitful area for future synthetic and biological research. PMID- 21970541 TI - Diffusion of polyphosphates into (poly(allylamine)-montmorillonite) multilayer films: flame retardant-intumescent films with improved oxygen barrier. AB - The present paper relies on the original idea to design multifunctional coatings, and in particular highly efficient intumescent flame retardant coatings, based on the diffusion of polyphosphates (PSPs) in exponentially growing "layer-by-layer" films made from montmorillonite (MMT) and poly(allylamine) (PAH). Here, we used polyphosphates as an acid source, polyallylamine as both a carbon source and a swelling agent, and finally clays to reinforce the intumescent char strength and also for their oxygen barrier property. The coatings made from the alternated deposition of n = 60 layer pairs of PAH and MMT reach a considerable thickness of ~18 MUm with well-defined ordering of the MMT in the direction parallel to the substrate. Structural, morphological, mechanical, gas barrier, and fire resistance properties of these films have been studied. Excellent oxygen barrier properties and extraordinary fire resistance properties are demonstrated based on the basis of a strong increase of the time to ignition and on a decrease of the heat release rate of polylactide substrates during mass loss calorimeter tests. This new and innovative intumescent flame retardant system based on (PAH-MMT)(n) PSP coatings is a promising universal treatment for current polymeric materials. PMID- 21970542 TI - Monodisperse Au11 clusters prepared by soft landing of mass selected ions. AB - Preparation of clean monodisperse samples of clusters and nanoparticles for characterization using cutting-edge analytical techniques is essential to understanding their size-dependent properties. Herein, we report a general method for the preparation of high surface coverage samples of monodisperse clusters containing an exact number of atoms. Polydisperse solutions of diphosphine-capped gold clusters were produced by reduction synthesis. Electrospray ionization was used to introduce the clusters into the gas phase where they were filtered by mass-to-charge ratio allowing clusters of a selected size to be deposited onto carbon coated copper grids at well controlled kinetic energies. Scanning transmission electron microscopy (STEM) analysis of the soft landed clusters confirms their monodispersity and high coverage on the substrate. The soft landing approach may be extended to other materials compatible with an array of available ionization techniques and, therefore, has widespread utility as a means for controlled preparation of monodisperse samples of nanoparticles and clusters for analysis by transmission electron microscopy (TEM). PMID- 21970543 TI - Selective formation of tungsten nanowires. AB - We report on a process for fabricating self-aligned tungsten (W) nanowires with polycrystalline silicon core. Tungsten nanowires as thin as 10 nm were formed by utilizing polysilicon sidewall transfer technology followed by selective deposition of tungsten by chemical vapor deposition (CVD) using WF6 as the precursor. With selective CVD, the process is self-limiting whereby the tungsten formation is confined to the polysilicon regions; hence, the nanowires are formed without the need for lithography or for additional processing. The fabricated tungsten nanowires were observed to be perfectly aligned, showing 100% selectivity to polysilicon and can be made to be electrically isolated from one another. The electrical conductivity of the nanowires was characterized to determine the effect of its physical dimensions. The conductivity for the tungsten nanowires were found to be 40% higher when compared to doped polysilicon nanowires of similar dimensions. PMID- 21970544 TI - High-strain-rate brain injury model using submerged acute rat brain tissue slices. AB - Blast-induced traumatic brain injury (bTBI) has received increasing attention in recent years due to ongoing military operations in Iraq and Afghanistan. Sudden impacts or explosive blasts generate stress and pressure waves that propagate at high velocities and affect sensitive neurological tissues. The immediate soft tissue response to these stress waves is difficult to assess using current in vivo imaging technologies. However, these stress waves and resultant stretching and shearing of tissue within the nano- to microsecond time scale of blast and impact are likely to cause initial injury. To visualize the effects of stress wave loading, we have developed a new ex vivo model in which living tissue slices from rat brain, attached to a ballistic gelatin substrate, were subjected to high strain-rate loads using a polymer split Hopkinson pressure bar (PSHPB) with real time high-speed imaging. In this study, average peak fluid pressure within the test chamber reached a value of 1584+/-63.3 psi. Cavitation due to a trailing underpressure wave was also observed. Time-resolved images of tissue deformation were collected and large maximum eigenstrains (0.03-0.42), minimum eigenstrains ( 0.33 to -0.03), maximum shear strains (0.09-0.45), and strain rates (8.4*103/sec) were estimated using digital image correlation (DIC). Injury at 4 and 6 h was quantified using Fluoro-Jade C. Neuronal injury due to PSHPB testing was found to be significantly greater than injury associated with the tissue slice paradigm alone. While large pressures and strains were encountered for these tests, this system provides a controllable test environment to study injury to submerged brain slices over a range of strain rate, pressure, and strain loads. PMID- 21970545 TI - A randomized controlled trial of the effect of rosiglitazone and clomiphene citrate versus clomiphene citrate alone in overweight/obese women with polycystic ovary syndrome. AB - BACKGROUND: In women suffering from polycystic ovary syndrome, correction of hyperinsulinemia results in enhanced responsiveness to ovulation induction agents. The effect of rosiglitazone was investigated on ovulation induction in obese women with PCOS. MATERIALS AND METHODS: A randomized controlled trial was set up. One hundred women were randomly assigned. Group A (n = 46) received rosiglitazone 4 mg b.i.d. plus clomiphene citrate (CC) 100 mg on cycle days 3-7. Group B (n = 45) received CC only. Primary outcome was ovulation. Secondary outcomes included pregnancy as well as changes in fasting glucose and insulin. RESULTS: Both groups were similar with respect to background and hormonal characteristics (age, duration of infertility, BMI, WHR, FSH, LH, E2, testosterone, fasting glucose and insulin). The cumulative ovulation rate over 12 weeks was significantly higher in group A (81.8%) than in group B (55.2%) (p < 0.001), whereas the difference in cumulative pregnancy rate was not statistically significant (30.4% versus 28.8%, respectively) in groups A and B (p = 0.946). Fasting insulin levels significantly declined after rosiglitazone therapy (p < 0.001) without change in glucose levels this resulted in normalization of the mean glucose to insulin ratio. CONCLUSIONS: Short term administration of rosiglitazone to overweight and obese PCOS women results in enhancement of CC induced ovulation as well as improvement of insulin sensitivity. PMID- 21970546 TI - Asymmetry, sex differences and age-related changes in the white matter in the healthy elderly: a tract-based study. AB - BACKGROUND: Hemispherical asymmetry, sex differences and age-related changes have been reported for the human brain. Meanwhile it was still unclear the presence of the asymmetry or sex differences in the human brain occurred whether as a normal development or as consequences of any pathological changes. The aim of this study was to investigate hemispherical asymmetry, sex differences and age-related changes by using a tract-based analysis in the nerve bundles. METHODS: 40 healthy elderly subjects underwent magnetic resonance diffusion tensor imaging, and we calculated fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values along the major white matter bundles. RESULTS: We identified hemispherical asymmetry in the ADC values for the cingulate fasciculus in the total subject set and in males, and a sex difference in the FA values for the right uncinate fasciculus. For age-related changes, we demonstrated a significant increase in ADC values with advancing age in the right cingulum, left temporal white matter, and a significant decrease in FA values in the right superior longitudinal fasciculus. CONCLUSION: In this study, we found hemispherical asymmetry, sex differences and age-related changes in particular regions of the white matter in the healthy elderly. Our results suggest considering these differences can be important in imaging studies. PMID- 21970547 TI - Process development for the elucidation of mycotoxin formation in Alternaria alternata. AB - The black mould Alternaria alternata produces a wide diversity of mycotoxins which are of particular health concern. Since no maximum allowable limits are set for Alternaria toxins in food and feed, prevention of Alternaria infestations and mycotoxin spoilage is the only way to avoid health risks. Thus, the understanding of mycotoxin biosynthesis is essential. For that purpose, a reliable batch process in a 2 L bioreactor was established which enables the study of several parameters influencing the production of the mycotoxins alternariol (AOH), alternariol monomethylether (AME) and tenuazonic acid (TA) by A. alternata DSM 12633. Modified Czapek-Dox medium was used with glucose as carbon source and ammonium and nitrate as nitrogen sources. Consumption of carbon and nitrogen sources as well as formation of the three mycotoxins were monitored; the average data of five independent fermentations was plotted and fitted using a logistic equation with four parameters. Maximum mycotoxin concentrations of 3.49 +/- 0.12 mg/L AOH, 1.62 +/- 0.14 mg/L AME and 38.28 +/- 0.1 mg/L TA were obtained.In this system the effect of different aeration rates (0.53 vvm-0.013 vvm) was tested which exerted a great influence on mycotoxin production. The use of the semi synthetic Czapek-Dox medium allowed the exchange of carbon and nitrogen sources for acetate and aspartic acid. The use of acetate instead of glucose resulted in the sole production of alternariol whereas the exchange of ammonium and nitrate for aspartate enhanced the production of both AOH and AME while TA production was not affected. PMID- 21970548 TI - Knowledge, perceptions and myths regarding infertility among selected adult population in Pakistan: a cross-sectional study. AB - BACKGROUND: The reported prevalence of infertility in Pakistan is approximately 22% with 4% primary and 18% secondary infertility. Infertility is not only a medical but also a social problem in our society as cultural customs and perceived religious dictums may equate infertility with failure on a personal, interpersonal, or social level. It is imperative that people have adequate knowledge about infertility so couples can seek timely medical care and misconceptions can be rectified. We aim to assess the knowledge, perception and myths regarding infertility and suggest ways to improve it. METHODS: A cross sectional survey was carried out by interviewing a sample of 447 adults who were accompanying the patients at two tertiary care hospitals in Karachi, Pakistan. They were interviewed one-on-one with the help of a pretested questionnaire drafted by the team after a thorough literature review and in consultation with infertility specialists. RESULTS: The correct knowledge of infertility was found to be limited amongst the participants. Only 25% correctly identified when infertility is pathological and only 46% knew about the fertile period in women's cycle. People are misinformed that use of IUCD (53%) and OCPs (61%) may cause infertility. Beliefs in evil forces and supernatural powers as a cause of infertility are still prevalent especially amongst people with lower level of education. Seeking alternative treatment for infertility remains a popular option for 28% of the participant as a primary preference and 75% as a secondary preference. IVF remains an unfamiliar (78%) and an unacceptable option (55%). CONCLUSIONS: Knowledge about infertility is limited in the population and a lot of misconceptions and myths are prevalent in the society. Alternative medicine is a popular option for seeking infertility treatment. The cultural and religious perspective about assisted reproductive technologies is unclear, which has resulted in its reduced acceptability. PMID- 21970550 TI - Natural taxanes: developments since 1828. PMID- 21970551 TI - Gallium nitride based logpile photonic crystals. AB - We demonstrate a nine-layer logpile three-dimensional photonic crystal (3DPC) composed of single crystalline gallium nitride (GaN) nanorods, ~100 nm in size with lattice constants of 260, 280, and 300 nm with photonic band gap in the visible region. This unique GaN structure is created through a combined approach of a layer-by-layer template fabrication technique and selective metal organic chemical vapor deposition (MOCVD). These GaN 3DPC exhibit a stacking direction band gap characterized by strong optical reflectance between 380 and 500 nm. By introducing a "line-defect" cavity in the fifth (middle) layer of the 3DPC, a localized transmission mode with a quality factor of 25-30 is also observed within the photonic band gap. The realization of a group III nitride 3DPC with uniform features and a band gap at wavelengths in the visible region is an important step toward realizing complete control of the electromagnetic environment for group III nitride based optoelectronic devices. PMID- 21970552 TI - Femtosecond rotational Raman coherence spectroscopy of cyclohexane in a pulsed supersonic jet. AB - We combine the technique of femtosecond degenerate four-wave mixing (fs-DFWM) with a high repetition-rate pulsed supersonic jet source to obtain the rotational coherence spectrum (RCS) of cold cyclohexane (C(6)H(12)) with high signal/noise ratio. In the jet expansion, the near-parallel flow pattern combined with rapid translational cooling effectively eliminate dephasing collisions, giving near constant RCS signal intensities over time delays up to 5 ns. The vibrational cooling in the jet eliminates the thermally populated vibrations that complicate the RCS coherences of cyclohexane at room temperature [Brugger, G.; et al. J. Phys. Chem. A 2011, 115, 9567]. The rotational cooling reduces the high-J rotational-state population, yielding the most accurate ground-state rotational constant to date, B(0) = 4305.859(9) MHz. Based on this B(0), a reanalysis of previous room-temperature gas-cell RCS measurements of cyclohexane gives improved vibration-rotation interaction constants for the nu(32), nu(6), nu(16), and nu(24) vibrational states. Combining the experimental B(0)(C(6)H(12)) with CCSD(T) calculations yields a very accurate semiexperimental equilibrium structure of the chair isomer of cyclohexane. PMID- 21970549 TI - Proteomic profiling of the influence of iron availability on Cryptococcus gattii. AB - Iron is essential and ubiquitous in living organisms. The competition for this micronutrient between the host and its pathogens has been related to disease establishment. Cryptococcus gattii is an encapsulated yeast that causes cryptococcosis mainly in immunocompetent individuals. In this study, we analyzed the proteomic profile of the C. gattii R265 Vancouver Island isolate under iron depleted and -repleted conditions by multidimensional protein identification technology (MudPIT) and by 2D-GE. Proteins and key mechanisms affected by alteration of iron levels such as capsule production, cAMP-signaling pathway, response to stress, and metabolic pathways related to mitochondrial function were identified. Our results also show both proteomic methodologies employed to be complementary. PMID- 21970553 TI - The relationship between oxidized lipoprotein(a) and carotid atherosclerosis in asymptomatic subjects: a comparison with native lipoprotein(a). AB - BACKGROUND: Oxidized lipoprotein(a) (oxLp(a)) can be a more potent marker of atherogenesis than native Lp(a), although Lp(a) is considered to be a risk factor for atherosclerotic diseases. Limited clinical data are available regarding the significance of oxLp(a) in atherosclerotic manifestations. This study aimed to investigate the association between the serum oxLp(a) and carotid artery intima media thickness (CIMT), in comparison to the serum Lp(a) levels, among asymptomatic subjects. METHODS: The atheroscrerosis-related variables including Lp(a) and oxLp(a) were measured in 136 cardiovascular disease-free subjects (61 males and 75 females, mean age of 64 years). The serum oxLp(a) level was quantified using a sandwich ELISA system. The CIMT level was ultrasonographically measured on bilateral carotid arteries. RESULTS: The median level of Lp(a) was 120 MUmol/L, oxLp(a) was 0.06 nmol/L, and CIMT was 0.7 mm, respectively. A simple correlation test showed that the CIMT was significantly and positively correlated with age, systolic blood pressure and oxLp(a) (r = 0.208, P < 0.05). A multiple linear regression analysis revealed that oxLp(a) continued to show a significant and positive correlation with the CIMT (beta = 0.202, P = 0.01). Although the similar analyses were conducted for Lp(a), it showed only a weak correlation with the CIMT (r = 0.011, beta = 0.041, both P < 0.05). CONCLUSIONS: These results suggest that oxLp(a) may be more closely associated with accelerated carotid atherosclerosis, in comparison to Lp(a), in this population. This finding can be important for obtaining a better understanding of the different atherogenic roles played by oxLp(a) in comparison to Lp(a). PMID- 21970554 TI - Attenuation of lung inflammation and fibrosis in CD69-deficient mice after intratracheal bleomycin. AB - BACKGROUND: Cluster of differentiation 69 (CD69), an early activation marker antigen on T and B cells, is also expressed on activated macrophages and neutrophils, suggesting that CD69 may play a role in inflammatory diseases. To determine the effect of CD69 deficiency on bleomycin(BLM)-induced lung injury, we evaluated the inflammatory response following intratracheal BLM administration and the subsequent fibrotic changes in wild type (WT) and CD69-deficient (CD69-/ ) mice. METHODS: The mice received a single dose of 3 mg/kg body weight of BLM and were sacrificed at 7 or 14 days post-instillation (dpi). Lung inflammation in the acute phase (7 dpi) was investigated by differential cell counts and cytokine array analyses of bronchoalveolar lavage fluid. In addition, lung fibrotic changes were evaluated at 14 dpi by histopathology and collagen assays. We also used reverse transcription polymerase chain reaction to measure the mRNA expression level of transforming growth factor beta1 (TGF-beta1) in the lungs of BLM-treated mice. RESULTS: CD69-/- mice exhibited less lung damage than WT mice, as shown by reductions in the following indices: (1) loss of body weight, (2) wet/dry ratio of lung, (3) cytokine levels in BALF, (4) histological evidence of lung injury, (5) lung collagen deposition, and (6) TGF-beta1 mRNA expression in the lung. CONCLUSION: The present study clearly demonstrates that CD69 plays an important role in the progression of lung injury induced by BLM. PMID- 21970555 TI - Evaluation of cardiovascular biomarkers in HIV-infected patients switching to abacavir or tenofovir based therapy. AB - BACKGROUND: Our objective was to evaluate and compare the effect of abacavir on levels of biomarkers associated with cardiovascular risk. METHODS: In an open label randomized trial, HIV-infected patients were randomized 1:1 to switch from zidovudine/lamivudine to abacavir/lamivudine or tenofovir/emtricitabine. In the present analysis, we measured levels of interleukin-6 (IL-6), high-sensitivity C reactive protein (hs-CRP), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), E-selectin, and myeloperoxidase (MPO) at baseline and 4, 12, and 48 weeks after randomization. D-dimer and fasting lipids were measured at baseline and weeks 12 and 48. Levels of biomarkers at all time points and changes from baseline were compared across study arms using Wilcoxon rank sum test. RESULTS: Of 40 included patients, 35 completed 48 weeks of randomized therapy and follow up. Levels of E-selectin (P=0.004) and sVCAM-1 (P=0.041) increased transiently from baseline to week 4 in the abacavir arm compared with the tenofovir arm, but no long-term increases were detected. We found no significant differences between study arms in the levels or changes in the levels of sICAM-1, MPO, d-dimer, IL-6, or hs-CRP. Levels of total cholesterol and high density lipoprotein (HDL) increased in the abacavir arm relative to the tenofovir arm, but no difference was found in total cholesterol/HDL ratio. CONCLUSION: In patients randomized to abacavir-based HIV treatment transient increases were seen in the plasma levels of E-selectin and sVCAM-1 compared with treatment with tenofovir, but no difference between study arms was found in other biomarkers associated with endothelial dysfunction, inflammation, or coagulation. The clinical significance of these findings is uncertain. TRIAL REGESTRATION: Clinicaltrials.gov identifier: NCT00647244. PMID- 21970556 TI - Attachment of CdSe nanoparticles to TiO2 via aqueous linker-assisted assembly: influence of molecular linkers on electronic properties and interfacial electron transfer. AB - CdSe nanoparticles (NPs) capped with cysteinate (Cys), 3-mercaptopropionate (MP), and mercaptosuccinate (MS) were adsorbed to TiO(2) from basic aqueous dispersions. Native capping groups served as molecular linkers to TiO(2). Thus, the materials-assembly chemistry was simplified and made more reproducible and environmentally benign. The electronic properties of CdSe and the electron transfer reactivity at CdSe-linker-TiO(2) interfaces varied with the structure and functionality of the capping groups. Cys-capped CdSe NPs exhibited a narrow and intense first excitonic absorption band centered at 422 nm, suggesting that they were magic-sized nanocrystals (MSCs) with diameters less than 2 nm. MP- and MS-capped CdSe NPs had broader and lower-energy absorption bands, which are typical of regular quantum dots. Photocurrent action spectra of nanocrystalline TiO(2) films functionalized with Cys-CdSe, MP-CdSe, and MS-CdSe overlaid closely with absorption spectra, indicating that excitation of CdSe gave rise to the injection of electrons into TiO(2). Under white-light illumination, the global energy-conversion efficiency for Cys-capped CdSe ((0.45 +/- 0.11)%) was 1.2-to-6 fold greater than for MP- and MS-capped CdSe. Similarly, the absorbed photon-to current efficiency was 1.3-to-3.3-fold greater. These differences arose from linker-dependent variations of electron-injection and charge-recombination reactivity. Transient absorption measurements indicated that electron injection from Cys-capped CdSe was more efficient than from MS-capped CdSe. In addition, charge recombination at CdSe-MS-TiO(2) interfaces was complete within hundreds of nanoseconds, whereas the charge-separated-state lifetime at CdSe-Cys-TiO(2) interfaces was on the order of several microseconds. Thus, Cys-capped CdSe MSCs are readily attached to TiO(2) and exhibit unusual electronic properties and desirable electron-transfer reactivity. PMID- 21970557 TI - Type and timing of menopause and later life mortality among women in the Iowa Established Populations for theEpidemiological Study of the Elderly (EPESE) cohort. AB - BACKGROUND: The relationship between menopausal characteristics and later life mortality is unclear. We tested the hypotheses that women with surgical menopause would have increased all-cause and cardiovascular mortality compared with women with natural menopause, and that women with earlier ages at natural or surgical menopause would have greater all-cause and cardiovascular mortality than women with later ages at menopause. METHODS: Women who participated in the Iowa cohort of the Established Populations for the Epidemiologic Study of the Elderly (n=1684) reported menopausal characteristics and potential confounding variables at baseline and were followed up for up to 24 years. Participants were aged 65 years or older at baseline and lived in rural areas. We used survival analysis to examine the relationships between menopausal characteristics and all-cause and cardiovascular mortality. RESULTS: A total of 1477 women (87.7% of respondents) died during the study interval. Women with an age at natural menopause >=55 years had increased all-cause and cardiovascular disease mortality compared with women who had natural menopause at younger ages. Type of menopause and age at surgical menopause were not related to mortality. These patterns persisted after adjustment for potential confounding variables. CONCLUSIONS: Among an older group of women from a rural area of the United States, later age at natural menopause was related to increased all-cause and cardiovascular mortality. Monitoring the cardiovascular health of this group of older women may contribute to improved survival times. PMID- 21970558 TI - Synthesis of a redox-responsive quadruple hydrogen-bonding unit for applications in supramolecular chemistry. AB - A redox-responsive quadruple hydrogen-bonding module (eDAN) has been developed. The strong binding between the reduced form and its partner (DeUG) can be significantly decreased upon oxidation but restored upon subsequent reduction. This on-off switch was successfully applied to provide reversible control of macroscopic supramolecular polymer networks. PMID- 21970559 TI - Detection of incoherent joint state due to inaccurate bone motion estimation. AB - In biomechanical modelling and motion analysis, the use of personalised data such as bone geometry would provide more accurate and reliable results. However, there are still a limited number of tools used to measure the evolution of articular interactions. This paper proposes a coherence index to describe the articular status of contact surfaces during motion. The index relies on a robust estimation of the evolution of surfacic interactions between the joint surfaces. The index is first compared to distance maps on simulated motions. It is then used to compare two motion capture protocols (two different localisations of the markers for scapula tracking). The results show that the index detects progressive modifications in the joint and allows distinguishing the two protocols, in accordance with the literature. In the future, the index could, among other things, be used to compare/improve biomechanical models and motion analysis protocols. PMID- 21970560 TI - Artifact quantification and tractography from 3T MRI after placement of aneurysm clips in subarachnoid hemorrhage patients. AB - BACKGROUND: The application of advanced 3T MRI imaging techniques to study recovery after subarachnoid hemorrhage (SAH) is complicated by the presence of image artifacts produced by implanted aneurysm clips. To characterize the effect of these artifacts on image quality, we sought to: 1) quantify extent of image artifact in SAH patients with implanted aneurysm clips across a range of MR sequences typically used in studies of volumetry, blood oxygen level dependent signal change (BOLD-fMRI), and diffusion-weighted imaging (DW-MRI) and 2) to explore the ability to reconstruct white matter pathways in these patients. METHODS: T1- and T2-weighted structural, BOLD-fMRI, and DW-MRI scans were acquired at 3T in two patients with titanium alloy clips in ACOM and left ACA respectively. Intensity-based planimetric contouring was performed on aligned image volumes to define each artifact. Artifact volumes were quantified by artifact/clip length and artifact/brain volume ratios and analyzed by two-way (scan-by-rater) ANOVAs. Tractography pathways were reconstructed from DW-MRI at varying distances from the artifacts using deterministic methods. RESULTS: Artifact volume varied by MR sequence for length (p = 0.007) and volume (p < 0.001) ratios: it was smallest for structural images, larger for DW-MRI acquisitions, and largest on fMRI images. Inter-rater reliability was high (r = 0.9626, p < 0.0001), and reconstruction of white matter connectivity characteristics increased with distance from the artifact border. In both patients, reconstructed white matter pathways of the uncinate fasciculus and inferior fronto-occipital fasciculus were clearly visible within 2 mm of the artifact border. CONCLUSIONS: Advanced 3T MR can successfully image brain tissue around implanted titanium aneurysm clips at different spatial ranges depending on sequence type. White matter pathways near clip artifacts can be reconstructed and visualized. These findings provide a reference for designing functional and structural neuroimaging studies of recovery in aSAH patients after clip placement. PMID- 21970561 TI - Physical structure of standing-up aromatic SAMs revealed by scanning tunneling microscopy. AB - Long-range-ordered aromatic SAMs are formed on Au(111) using 4-nitrophenyl sulfenyl chloride as a precursor. Although the main structure is a ?3 * ?3 with a molecular density similar to that usually found for aliphatic SAMs, particular spots presenting specific shapes are also observed by STM. These include hexagons, partial hexagons, parallelograms, and zigzags resulting from specific arrangements of adsorbed molecules. These molecular arrangements are reversible as they form and dissociate or "vanish" in various areas on the surface. STM shows that these particular structures provide some order to their surrounding because areas void of these structures look less ordered. More interestingly, STM shows submolecular details of the molecules involved in forming these structures, hence providing direct experimental evidence for the ability of the STM to provide physical structure information of standing up SAMs. This is indeed a heavily debated question, and this work reports the first experimental example where submolecular physical structure is revealed by STM for standing-up SAMs. PMID- 21970563 TI - Neuromuscular blockers and ARDS: thou shalt not breathe, move, or die! PMID- 21970562 TI - Quantitative CT improves outcome prediction in acute traumatic brain injury. AB - The admission noncontrast head computed tomography (CT) scan has been demonstrated to be one of several key early clinical and imaging features in the challenging problem of prediction of long-term outcome after acute traumatic brain injury (TBI). In this study, we employ two novel approaches to the problem of imaging classification and outcome prediction in acute TBI. First, we employ the novel technique of quantitative CT (qCT) image analysis to provide more objective, reproducible measures of the abnormal features of the admission head CT in acute TBI. We show that the incorporation of quantitative, rather than qualitative, CT features results in a significant improvement in prediction of the 6-month Extended Glasgow Outcome Scale (GOS-E) score over a wide spectrum of injury severity. Second, we employ principal components analysis (PCA) to demonstrate the interdependence of certain predictive variables. Relatively few prior studies of outcome prediction in acute TBI have used a multivariate approach that explicitly takes into account the potential covariance among clinical and CT predictive variables. We demonstrate that several predictors, including midline shift, cistern effacement, subdural hematoma volume, and Glasgow Coma Scale (GCS) score are related to one another. Rather than being independent features, their importance may be related to their status as surrogate measures of a more fundamental underlying clinical feature, such as the severity of intracranial mass effect. We believe that objective computational tools and data-driven analytical methods hold great promise for neurotrauma research, and may ultimately have a role in image analysis for clinical care. PMID- 21970565 TI - An Internet-based osteoporotic fracture risk program: effect on knowledge, attitudes, and behaviors. AB - OBJECTIVE: The 2004 Surgeon General's Bone Health Report calls for innovative interventions to reduce osteoporotic fracture. We developed an Internet-based risk- and stage-tailored intervention to promote self-management of fracture risk. METHODS: We randomized 121 women to receive 18 personalized Internet-based tutorials with behavior modification strategies for nutrition, exercise, and other behaviors (n=61) or to receive standard information (n=60). Tutorials were tailored for 10-year hip fracture risk, osteoporosis knowledge, attitudes about osteoporosis, nutritional intake, and exercise levels. Participants in both groups completed questionnaires at baseline, 3 months, and 6 months. Qualitative data included tutorial evaluation forms and focus groups. Main outcomes were perceived impact of the intervention, and changes in osteoporosis knowledge and beliefs, calcium and vitamin D intake, and exercise levels. RESULTS: At 6 months, 80% of intervention and 92% of control group participants completed the study. The intervention group significantly increased general osteoporosis knowledge (p=0.03) and calcium knowledge (p=0.02) compared with the control group. At 6 months, intervention participants were not significantly more likely to meet recommendations for calcium (OR: 1.39; 95% CI: 0.64-3.0; p=0.40), vitamin D (OR: 1.27; CI: 0.61-2.66; p=0.53), or aerobic (OR: 1.49; 95% CI: 0.63-3.48; p=0.36) or resistance exercise (OR: 1.36; 95% CI: 0.66-2.79; p=0.40) compared with control group participants. Thematic analyses of two focus groups and 794 tutorial evaluation forms, however, indicated that the intervention improved participant ability to implement and maintain healthy behaviors. Participants suggested program refinements including virtual support groups, applications for portable devices, and tailoring of tutorial length. CONCLUSION: The risk- and stage tailored intervention was associated with improved knowledge but was not associated with significant behavioral improvements. Qualitative results suggest the intervention improved behavior implementation and maintenance. A refined intervention with additional tailoring capabilities could be used with Internet based fracture risk assessment tools to confront the growing societal burden of osteoporotic fractures. PMID- 21970564 TI - Breast cancer knowledge, attitudes, and early detection practices in United States-Mexico border Latinas. AB - INTRODUCTION: Evidence suggests Latinas residing along the United States-Mexico border face higher breast cancer mortality rates compared to Latinas in the interior of either country. The purpose of this study was to investigate breast cancer knowledge, attitudes, and use of breast cancer preventive screening among U.S. Latina and Mexican women residing along the U.S.-Mexico border. METHODS: For this binational cross-sectional study, 265 participants completed an interviewer administered questionnaire that obtained information on sociodemographic characteristics, knowledge, attitudes, family history, and screening practices. Differences between Mexican (n=128) and U.S. Latina (n=137) participants were assessed by Pearson's chi-square, Fischer's exact test, t tests, and multivariate regression analyses. RESULTS: U.S. Latinas had significantly increased odds of having ever received a mammogram/breast ultrasound (adjusted odds ratio [OR]=2.95) and clinical breast examination (OR=2.67) compared to Mexican participants. A significantly greater proportion of Mexican women had high knowledge levels (54.8%) compared to U.S. Latinas (45.2%, p<0.05). Age, education, and insurance status were significantly associated with breast cancer screening use. CONCLUSIONS: Despite having higher levels of breast cancer knowledge than U.S. Latinas, Mexican women along the U.S.-Mexico border are not receiving the recommended breast cancer screening procedures. Although U.S. border Latinas had higher breast cancer screening levels than their Mexican counterparts, these levels are lower than those seen among the general U.S. Latina population. Our findings underscore the lack of access to breast cancer prevention screening services and emphasize the need to ensure that existing breast cancer screening programs are effective in reaching women along the U.S. Mexico border. PMID- 21970566 TI - Self-assessment of fluid intake behavior in women with urinary incontinence. AB - OBJECTIVE: To determine if women with urinary incontinence are able to recognize patterns of fluid intake associated with lower urinary tract symptoms. METHODS: We performed a cross-sectional study of 256 consecutive women with urinary incontinence at an initial visit to a urogynecology practice. Data from the Questionnaire-Based Voiding Diary, a validated instrument that measures volume of fluid intake, fluid intake behavior, and lower urinary tract symptoms, were abstracted. Carbonated, caffeinated, and total fluid intake volumes were analyzed. Behaviors of excess consumption of caffeinated, carbonated, and total fluid intake as well as restriction of fluid intake were measured. Fluid intake volumes were divided into quartiles and correlated to fluid intake behavior and lower urinary tract symptoms. RESULTS: Fluid intake behaviors of drinking excess carbonated and caffeinated beverages were significantly associated with the volume of carbonated (p<0.001) and caffeinated fluid intake (p<0.001). The behavior of drinking excess fluid was significantly associated with the total volume of fluid intake (p=0.019). A significant relationship between quartiles of total fluid intake and increasing number of daily voids (p<0.001) and quartiles of caffeinated fluid intake and increasing severity of urgency urinary incontinence (p=0.038) was noted. A direct statistical association between fluid intake behavior and lower urinary tract symptoms was not noted. CONCLUSIONS: Women with urinary incontinence recognize their pattern of fluid intake and fluid intake behavior. The type and volume of fluid intake are significantly associated with symptoms of urinary frequency and urgency urinary incontinence. PMID- 21970567 TI - Identification and fine-mapping of Xa33, a novel gene for resistance to Xanthomonas oryzae pv. oryzae. AB - Broadening of the genetic base for identification and transfer of genes for resistance to insect pests and diseases from wild relatives of rice is an important strategy in resistance breeding programs across the world. An accession of Oryza nivara, International Rice Germplasm Collection (IRGC) accession number 105710, was identified to exhibit high level and broad-spectrum resistance to Xanthomonas oryzae pv. oryzae. In order to study the genetics of resistance and to tag and map the resistance gene or genes present in IRGC 105710, it was crossed with the bacterial blight (BB)-susceptible varieties 'TN1' and 'Samba Mahsuri' (SM) and then backcrossed to generate backcross mapping populations. Analysis of these populations and their progeny testing revealed that a single dominant gene controls resistance in IRGC 105710. The BC(1)F(2) population derived from the cross IRGC 105710/TN1//TN1 was screened with a set of 72 polymorphic simple-sequence repeat (SSR) markers distributed across the rice genome and the resistance gene was coarse mapped on chromosome 7 between the SSR markers RM5711 and RM6728 at a genetic distance of 17.0 and 19.3 centimorgans (cM), respectively. After analysis involving 49 SSR markers located between the genomic interval spanned by RM5711 and RM6728, and BC(2)F(2) population consisting of 2,011 individuals derived from the cross IRGC 105710/TN1//TN1, the gene was fine mapped between two SSR markers (RMWR7.1 and RMWR7.6) located at a genetic distance of 0.9 and 1.2 cM, respectively, from the gene and flanking it. The linkage distances were validated in a BC(1)F(2) mapping population derived from the cross IRGC 105710/SM//2 * SM. The BB resistance gene present in the O. nivara accession was identified to be novel based on its unique map location on chromosome 7 and wider spectrum of BB resistance; this gene has been named Xa33. The genomic region between the two closely flanking SSR markers was in silico analyzed for putatively expressed candidate genes. In total, eight genes were identified in the region and a putative gene encoding serinethreonine kinase appears to be a candidate for the Xa33 gene. PMID- 21970568 TI - Molecular identification of two vegetative compatibility groups of Fusarium oxysporum f. sp. cepae. AB - Fusarium oxysporum f. sp. cepae, which causes basal rot of onion, consists of seven vegetative compatibility groups (VCGs 0420 to 0426) and several single member VCGs (SMVs). F. oxysporum f. sp. cepae populations in South Africa and Colorado each consist of one main VCG (namely, VCG 0425 and 0421, respectively). The aim of this study was to develop sequence-characterized amplified region (SCAR) markers for the identification of VCGs 0425 and 0421, using 79 previously characterized F. oxysporum isolates. A second aim was to investigate the prevalence of VCG 0425 among 88 uncharacterized South African onion F. oxysporum isolates using (i) the developed SCAR markers and (ii) inter-retrotransposon (IR) and random amplified polymorphic DNA (RAPD) fingerprinting. Only two RAPD primers provided informative fingerprints for VCG 0425 isolates but these could not be developed into SCAR markers, although they provided diagnostic fragments for differentiation of VCG 0425 from VCG 0421. IR fingerprinting data were used to develop a multiplex IR-SCAR polymerase chain reaction method for the identification of VCG 0421, VCG 0425, and SMV 4 isolates as a group. Molecular identification of the uncharacterized collection of 88 F. oxysporum isolates (65 F. oxysporum f. sp. cepae and 23 F. oxysporum isolates nonpathogenic to onion) confirmed that VCG 0425 is the main VCG in South Africa, with all but 3 of the 65 F. oxysporum f. sp. cepae isolates having the molecular characteristics of this VCG. Genotyping and VCG testing showed that two of the three aforementioned isolates were new SMVs (SMV 6 and SMV 7), whereas the third (previously known as SMV 3) now belongs to VGC 0247. PMID- 21970569 TI - Aluminum for nonlinear plasmonics: resonance-driven polarized luminescence of Al, Ag, and Au nanoantennas. AB - Resonant optical antennas are ideal for nanoscale nonlinear optical interactions due to their inherent strong local field enhancement. Indeed second- and third order nonlinear response of gold nanoparticles has been reported. Here we compare the on- and off-resonance properties of aluminum, silver, and gold nanoantennas, by measuring two-photon photoluminescence. Remarkably, aluminum shows 2 orders of magnitude higher luminescence efficiency than silver or gold. Moreover, in striking contrast to gold, the aluminum emission largely preserves the linear incident polarization. Finally, we show the systematic resonance control of two photon excitation and luminescence polarization by tuning the antenna width and length independently. Our findings point to aluminum as a promising metal for nonlinear plasmonics. PMID- 21970570 TI - Small mass-change detectable quartz crystal microbalance and its application to enzymatic one-base elongation on DNA. AB - A highly sensitive 27 MHz quartz crystal microbalance instrument with an automatic flow injection system was developed to obtain realistic minimal frequency noise (+/-0.05 Hz) and to obtain a stable signal baseline (+/-1 Hz/h) by controlling the temperature of each part in the quartz crystal microbalance (QCM) system using three Peltier devices with a resolution of +/-0.001 degrees C and by optimizing the flow system to prevent fluctuation of the internal pressure of the QCM. The improved QCM with an automatic flow injection system enabled detection of small mass changes such as binding of biotin to a streptavidin immobilized QCM with a high signal-to-noise ratio. We also applied this device to enzyme reactions of one-base elongation by DNA polymerase (Klenow fragment, KF). We immobilized dsDNAs including the protruding end of dA, dG, dT, or dC on the QCM electrode and ran complementary dNTP monomers with KF into the QCM flow cell. We could directly detect the enzymatic one-base elongation of DNA as a small mass increase, and we found the difference in the reaction rate for each monomer. PMID- 21970571 TI - Dietary use and conservation concern of edible wetland plants at Indo-Burma hotspot: a case study from Northeast India. AB - BACKGROUND: The wetlands of the North East India fall among the global hotspots of biodiversity. However, they have received very little attention with relation to their intrinsic values to human kind; therefore their conservation is hardly addressed. These wetlands are critical for the sustenance of the tribal communities. METHODS: Field research was conducted during 2003 to 2006 in seven major wetlands of four districts of Manipur state, Northeast India (viz. Imphal East, Imphal-West, Thoubal, and Bishnupur). A total of 224 wetland-plant collectors were interviewed for the use and economics of species using semi structured questionnaires and interview schedules. Imphal, Bishenpur and Thoubal markets were investigated in detail for influx and consumption pattern of these plants. The collectors were also inquired for medicinal use of wetland species. Nutritive values of 21 species were analyzed in laboratory. The vouchers were collected for all the species and deposited in the CSIR-NEIST (Formerly Regional Research Laboratory), Substation, Lamphelpat, Imphal, Manipur, India. RESULTS: We recorded 51 edible wetland species used by indigenous people for food and medicinal purposes. Thirty eight species had high medicinal values and used in the traditional system to treat over 22 diseases. At least 27 species were traded in three markets studied (i.e. Imphal, Thoubal and Bishenpur), involving an annual turnover of 113 tons of wetland edible plants and a gross revenue of Rs. 907, 770/- (US$1 = Rs. 45/-). The Imphal market alone supplies 60% of the total business. Eighty per cent of the above mentioned species are very often used by the community. The community has a general opinion that the availability of 45% species has depleted in recent times, 15 species need consideration for conservation while another 7 species deserved immediate protection measures. The nutrient analysis showed that these species contribute to the dietary balance of tribal communities. CONCLUSIONS: Considering the importance of wild wetland plants in local sustenance, it is suggested to protect their habitats, develop domestication protocols of selected species, and build programs for the long-term management of wetland areas by involving local people. Some medicinal plants may also be used to develop into modern medicines. PMID- 21970572 TI - The footprints of gut microbial-mammalian co-metabolism. AB - Gut microbiota are associated with essential various biological functions in humans through a "network" of microbial-host co-metabolism to process nutrients and drugs and modulate the activities of multiple pathways in organ systems that are linked to different diseases. The microbiome impacts strongly on the metabolic phenotypes of the host, and hence, metabolic readouts can give insights into functional metagenomic activity. We applied an untargeted mass spectrometry (MS) based metabonomics approach to profile normal Wistar rats exposed to a broad spectrum beta-lactam antibiotic imipenem/cilastatin sodium, at 50 mg/kg/daily for 4 days followed by a 14-day recovery period. In-depth metabolic phenotyping allowed identification of a panel of 202 urinary and 223 fecal metabolites significantly related to end points of a functional metagenome (p < 0.05 in at least one day), many of which have not been previously reported such as oligopeptides and carbohydrates. This study shows extensive gut microbiota modulation of host systemic metabolism involving short-chain fatty acids, tryptophan, tyrosine metabolism, and possibly a compensatory mechanism of indole melatonin production. Given the integral nature of the mammalian genome and metagenome, this panel of metabolites will provide a new platform for potential therapeutic markers and mechanistic solutions to complex problems commonly encountered in pathology, toxicology, or drug metabolism studies. PMID- 21970573 TI - Telehealth practice recommendations for diabetic retinopathy, second edition. AB - Ocular telemedicine and telehealth have the potential to decrease vision loss from DR. Planning, execution, and follow-up are key factors for success. Telemedicine is complex, requiring the services of expert teams working collaboratively to provide care matching the quality of conventional clinical settings. Improving access and outcomes, however, makes telemedicine a valuable tool for our diabetic patients. Programs that focus on patient needs, consider available resources, define clear goals, promote informed expectations, appropriately train personnel, and adhere to regulatory and statutory requirements have the highest chance of achieving success. PMID- 21970574 TI - Regional adiposity distribution and insulin resistance in young Chinese and European Australian women. AB - OBJECTIVE: Lower than normal leg fat mass and excessive trunk fat mass are predictive of insulin resistance (IR) in obese women of European descent. Whether this regional adiposity relationship applies to moderately overweight women of Chinese descent is undetermined. Thus, the relationship between leg and trunk fat mass and IR of young (22.3 +/- 0.3 years) sedentary Australian women of either Chinese (CW; n = 22) or European (EW; n = 36) descent was examined. MATERIAL AND METHODS: Subjects underwent a maximal oxygen uptake test, blood draw, and dual energy x-ray absorptiometry to measure body composition. Fasting insulin levels and C-reactive protein (CRP) were assessed by ELISA and IR was calculated by HOMA IR. Blood lipids and glucose were quantified by an automated enzymatic method (Cholestech LDX, USA). RESULTS: Total, arm, trunk, and leg fat was significantly greater (p < 0.05) for the EW group, whereas IR was significantly higher for CW. Fasting lipids and glucose were within normal levels for both groups, whereas CRP levels were significantly higher in EW. For EW trunk fat mass was the only variable significantly correlated with IR (r = 0.40, p < 0.05). In contrast, for CW leg fat mass was significantly correlated with IR (r = - 0.49, p < 0.05). CONCLUSIONS: Greater trunk fat mass was associated with higher IR of Australian women of European descent, whereas smaller leg fat mass was associated with higher IR of women of Chinese descent. PMID- 21970575 TI - High sensitivity C-reactive protein and its relationship with impaired glucose regulation in lean patients with polycystic ovary syndrome. AB - The polycystic ovary syndrome (PCOS) is the most common endocrine-metabolic disorder, also associated with the metabolic syndrome. Serum high sensitivity C reactive protein (hs-CRP), a marker of low-grade chronic inflammation is a potent predictor of cardiovascular events, closely linked to metabolic syndrome features and higher in patients with PCOS. However, hs-CRP in lean patients with PCOS has not been fully evaluated and few data are available. We aimed to investigate the relation between glucose intolerance and hs-CRP levels in lean patients with PCOS, and to evaluate the possible relationship between hs-CRP and PCOS by evaluating PCOS-related metabolic abnormalities in Korean women. We consecutively recruited 115 lean (BMI < 25kg/m(2)) patients diagnosed with PCOS and 103 lean healthy controls. The PCOS group was divided two groups: impaired glucose regulation (IGR) and normal glucose tolerance group (NGT). In lean patients with PCOS, hs-CRP level was higher in the IGR group than in the NGT group (0.60 +/- 1.37 versus 0.18 +/- 0.46, p(Bonf) = 0.023) and other metabolic risk factors were also higher in the IGR group than in the NGT group. And there were close relationships between hs-CRP level and metabolic risk factor, such as 2 h postprandial insulin level in the lean patients with PCOS. PMID- 21970576 TI - Antiphospholipid antibodies in black south africans with hiv and acute coronary syndromes: prevalence and clinical correlates. AB - BACKGROUND: HIV infection is associated with a high prevalence of antiphospholipid antibodies (aPL) and increased thrombotic events but the aetiopathogenic link between the two is unclear. FINDINGS: Prospective single centre study from Soweto, South Africa, comparing the prevalence of aPL in highly active anti-retroviral therapy (HAART) naive HIV positive and negative patients presenting with Acute Coronary Syndromes (ACS). Between March 2004 and February 2008, 30 consecutive black South African HIV patients with ACS were compared to 30 black HIV negative patients with ACS. The HIV patients were younger (43 +/- 7 vs. 54 +/- 13, p = 0.004) and besides smoking (73% vs. 33%, p = 0.002) and lower HDL levels (0.8 +/- 0.3 vs. 1.1 +/- 0.4, p = 0.001) had fewer risk factors than the control group. HIV patients had a higher prevalence of anticardiolipin (aCL) IgG (47% vs. 10%, p = 0.003) and anti-prothrombin (aPT) IgG antibodies (87% vs. 21%, p < 0.001) but there was no difference in the prevalence of the antiphospholipid syndrome (44% vs. 24%, p = N/S) and aPL were not predictive of clinical or angiographic outcomes. CONCLUSIONS: Treatment naive black South African HIV patients with ACS are younger with fewer traditional coronary risk factors than HIV negative patients but have a higher prevalence and different expression of aPL which is likely to be an epiphenomenon of the HIV infection rather than causally linked to thrombosis and the pathogenesis of ACS. PMID- 21970577 TI - Factor analysis of self-treatment in diabetes mellitus: a cross-sectional study. AB - BACKGROUND: Self-treatment is a treatment of oneself without professional help, which may cause health-related consequences. This investigation examined the self treatment behaviors in patients with diabetes mellitus in Iran/kashan. METHODS: The patients who referred to the clinic of diabetes and those who were admitted to the General hospital in the city of Kashan due to diabetes mellitus were asked to participate in this cross-sectional study. For data collection, The 25 item questionnaire of Likert scale type with four scales was used. Factor analysis was performed to define the patterns of self-treatment. RESULTS: 398 patients participated in the study. The mean age of the study population was 54.9 +/- 12.9 years. The majority (97%) had type 2 diabetes. 50% of patients reported self- treatment. The self-treatment score was 45.8 +/- 8.8 (25-100). Female gender, lower education and co-morbid illnesses of hypertension, hyperlipidemia and cardiac disease had significant relationship with self-treatment. The factor analysis procedure revealed seven factors that explained the 43% of variation in the self-treatment. These seven factors were categorized as knowledge, deficiencies of formal treatments, available self-treatment methods, physician related factors, the tendency to use herbal remedies, underlying factors such as gender and factors related to diabetes. CONCLUSIONS: There is a medium tendency for self-treatment in diabetic patients. The assessment of self-treatment practices must be an essential part of patients' management in diabetes care. PMID- 21970578 TI - 3D positioning scheme exploiting nano-scale IR-UWB orthogonal pulses. AB - In these days, the development of positioning technology for realizing ubiquitous environments has become one of the most important issues. The Global Positioning System (GPS) is a well-known positioning scheme, but it is not suitable for positioning in in-door/building environments because it is difficult to maintain line-of-sight condition between satellites and a GPS receiver. To such problem, various positioning methods such as RFID, WLAN, ZigBee, and Bluetooth have been developed for indoor positioning scheme. However, the majority of positioning schemes are focused on the two-dimension positioning even though three-dimension (3D) positioning information is more useful especially in indoor applications, such as smart space, U-health service, context aware service, etc. In this paper, a 3D positioning system based on mutually orthogonal nano-scale impulse radio ultra-wideband (IR-UWB) signals and cross array antenna is proposed. The proposed scheme uses nano-scale IR-UWB signals providing fine time resolution and high-resolution multiple signal specification algorithm for the time-of-arrival and the angle-of-arrival estimation. The performance is evaluated over various IEEE 802.15.4a channel models, and simulation results show the effectiveness of proposed scheme. PMID- 21970587 TI - Surgical treatment of intracystic carcinoma of the breast. AB - BACKGROUND: Intracystic carcinoma of the breast is a type of breast cancer with favorable prognosis where cancer arises from the cystic wall. However, it is a relatively rare disease, and no general consensus has been reached on its definition, including pathogenesis, extramural invasion, and lymph node metastasis. METHODS: Six patients who underwent surgery at the Department of Surgery at Asahikawa Medical University are presented. In each patient, background factors, diagnosis, surgery, pathological diagnosis, and prognosis were investigated. RESULTS: Fine needle aspiration showed class V disease in three patients and class III disease in the other three, and lumpectomy was performed for class III patients. Three patients underwent breast-conserving surgery While extramural invasion was seen in three patients, lymph node metastasis was absent in all patients. CONCLUSION: When it is difficult to diagnose intracystic carcinoma of the breast by fine needle aspiration, active lumpectomy is necessary. Because extramural invasion and lymph node metastasis have been reported, it is necessary to carefully determine the range of excision and rationally perform lymph node dissection, such as sentinel node biopsy. PMID- 21970588 TI - pH-dependent network formation of quantum dots and fluorescent quenching by Au nanoparticle embedding. AB - A simple approach to the creation of colloidal assemblies is in high demand for the development of functional devices. Here, we present the preparation of CdTe QD (quantum dot) networks in as little as 1 day simply by pH modification without the use of oxidants. The QD network was tractable in water and casting from a droplet produced a porous networked film on both hydrophobic and hydrophilic solid substrates. Further, we found that citrate-protected gold nanoparticles (AuNPs, d = 5 nm) could be incorporated into the QD networks to afford a QD/Au composite network, and that the fluorescence from the QDs was largely decreased by the addition of a small proportion of AuNPs (QD:AuNP = 99.4:0.6), probably due to the efficient charge transfer through the network. These data indicate that our method is suitable for application to the creation of metal/QD hybrid materials that can be integrated into wet-based processes. PMID- 21970589 TI - Comparison of adverse drug reaction profiles of two tacrolimus formulations in rats. AB - Tacrobell((r)) (TB) is a generic tacrolimus which showed the comparable efficacy to original product, Prograf((r)) (PG) in renal transplantation, but toxicity between two drugs is unclear. The aim of this study was to compare the toxicity between these two formulations. TB and PG (0.5, 1 and 2 mg/kg/day) was administered to rats for 4 weeks. The rat survival rate, kidney, liver and pancreas injury was investigated. The survival rate was similar between TB- and PG-treated rats. TB and PG induced renal dysfunction in a dose-dependent manner. Compared to PG treatment in equal dose, TB treatment reduced urinary creatinine clearance in a less degree and renal interstitial fibrosis was comparable between two regimens. The r-glutamyl transpeptidase was aggravated by tacrolimus treatment, and this was not different between TB and PG treatment. In the intraperitoneal glucose tolerance test, a significant diabetogenic effect was observed in all tacrolimus treated-rats. The glucose tolerance of TB-treated rats was similar to those of PG-treated rats in each dose. The decrement in pancreatic beta-cell mass by tacrolimus showed the dose-dependent response and it was comparable between TB and PG treatment. In conclusion, TB is similar to PG in terms of nephrotoxicity, hepatoxicity and diabetogenic effect. PMID- 21970590 TI - Morphological and genetic divergence in Swedish postglacial stickleback (Pungitius pungitius) populations. AB - BACKGROUND: An important objective of evolutionary biology is to understand the processes that govern phenotypic variation in natural populations. We assessed patterns of morphological and genetic divergence among coastal and inland lake populations of nine-spined stickleback in northern Sweden. Coastal populations are either from the Baltic coast (n = 5) or from nearby coastal lakes (n = 3) that became isolated from the Baltic Sea (< 100 years before present, ybp). Inland populations are from freshwater lakes that became isolated from the Baltic approximately 10,000 ybp; either single species lakes without predators (n = 5), or lakes with a recent history of predation (n = 5) from stocking of salmonid predators (~50 ybp). RESULTS: Coastal populations showed little variation in 11 morphological traits and had longer spines per unit of body length than inland populations. Inland populations were larger, on average, and showed greater morphological variation than coastal populations. A principal component analysis (PCA) across all populations revealed two major morphological axes related to spine length (PC1, 47.7% variation) and body size (PC2, 32.9% variation). Analysis of PCA scores showed marked similarity in coastal (Baltic coast and coastal lake) populations. PCA scores indicate that inland populations with predators have higher within-group variance in spine length and lower within group variance in body size than inland populations without predators. Estimates of within-group PST (a proxy for QST) from PCA scores are similar to estimates of FST for coastal lake populations but PST >FST for Baltic coast populations. PST >FST for PC1 and PC2 for inland predator and inland no predator populations, with the exception that PST 5% quench response). We report the key finding that the brightest SWNTs are not the best transducers of glycan binding. SWNTs ranging in intensity between 50 and 75% of the maximum show the greatest response. The ability to pinpoint strong-binding, single sensors is promising to build a nanoarray of glycan-lectin transducers as a high throughput method to profile glycans without protein labeling or glycan liberation pretreatment steps. PMID- 21970595 TI - Characterisation of electrophysiological conduction in cardiomyocyte co-cultures using co-occurrence analysis. AB - Cardiac arrhythmias are disturbances of the electrical conduction pattern in the heart with severe clinical implications. The damage of existing cells or the transplantation of foreign cells may disturb functional conduction pathways and may increase the risk of arrhythmias. Although these conduction disturbances are easily accessible with the human eye, there is no algorithmic method to extract quantitative features that quickly portray the conduction pattern. Here, we show that co-occurrence analysis, a well-established method for feature recognition in texture analysis, provides insightful quantitative information about the uniformity and the homogeneity of an excitation wave. As a first proof-of principle, we illustrate the potential of co-occurrence analysis by means of conduction patterns of cardiomyocyte-fibroblast co-cultures, generated both in vitro and in silico. To characterise signal propagation in vitro, we perform a conduction analysis of co-cultured murine HL-1 cardiomyocytes and murine 3T3 fibroblasts using microelectrode arrays. To characterise signal propagation in silico, we establish a conduction analysis of co-cultured electrically active, conductive cardiomyocytes and non-conductive fibroblasts using the finite element method. Our results demonstrate that co-occurrence analysis is a powerful tool to create purity-conduction relationships and to quickly quantify conduction patterns in terms of co-occurrence energy and contrast. We anticipate this first preliminary study to be a starting point for more sophisticated analyses of different co-culture systems. In particular, in view of stem cell therapies, we expect co-occurrence analysis to provide valuable quantitative insight into the integration of foreign cells into a functional host system. PMID- 21970597 TI - Evidence for cosmetics as a source of mineral oil contamination in women. AB - BACKGROUND: There is strong evidence that mineral oil hydrocarbons are the greatest contaminant of the human body, amounting to approximately 1 g per person. Possible routes of contamination include air inhalation, food intake, and dermal absorption. The present study aims to identify the most relevant sources of mineral oil contamination. METHODS: One hundred forty-two women undergoing elective cesarean section were enrolled. A specimen of subcutaneous fat was removed prior to wound closure. On days 4 and 20 postpartum, milk samples were collected from the women. Fat and milk samples were analyzed for mineral oil saturated hydrocarbons (MOSH). All women completed a questionnaire on personal data, nutrition habits, and use of cosmetics. MOSH concentrations in fat tissue were compared with data from the questionnaire and with MOSH concentrations in corresponding milk samples. RESULTS: The predominant predictor for MOSH contamination of fat tissue was age (p<0.001). Furthermore, body mass index (p=0.001), country of main residence (p=0.03), number of previous childbirths (p=0.029), use of sun creams in the present pregnancy (p=0.002), and use of hand creams and lipsticks in daily life (p=0.011 and p=0.007, respectively) were significant independent determinants. No association was found with nutritional habits. A strong correlation was seen between MOSH concentration in fat tissue (median 52.5 mg/kg) and in the corresponding milk fat sample from day 4 (median 30 mg/kg) (p<0.001) and day 20 (median 10 mg/kg) (p=0.028). CONCLUSIONS: The increase in MOSH concentration in human fat tissue with age suggests an accumulation over time. Cosmetics might be a relevant source of the contamination. PMID- 21970596 TI - Pharmacogenetic testing affects choice of therapy among women considering tamoxifen treatment. AB - BACKGROUND: Pharmacogenetic testing holds major promise in allowing physicians to tailor therapy to patients based on genotype. However, there is little data on the impact of pharmacogenetic test results on patient and clinician choice of therapy. CYP2D6 testing among tamoxifen users offers a potential test case of the use of pharmacogenetic testing in the clinic. We evaluated the effect of CYP2D6 testing in clinical practice to determine whether genotype results affected choice of hormone therapy in a prospective cohort study. METHODS: Women planning to take or currently taking tamoxifen were considered eligible. Participants were enrolled in an informational session that reviewed the results of studies of CYP2D6 genotype on breast cancer recurrence. CYP2D6 genotyping was offered to participants using the AmpliChip CYP450 Test. Women were classified as either poor, intermediate, extensive or ultra-rapid metabolizers. Results were provided to clinicians without specific treatment recommendations. Follow-up was performed with a structured phone interview 3 to 6 months after testing to evaluate changes in medication. RESULTS: A total of 245 women were tested and 235 completed the follow-up survey. Six of 13 (46%) women classified as poor metabolizers reported changing treatment compared with 11 of 218 (5%) classified as intermediate, extensive or ultra-rapid metabolizers (P < 0.001). There was no difference in treatment choices between women classified as intermediate and extensive metabolizers. In multi-variate models that adjusted for age, race/ethnicity, educational status, method of referral into the study, prior knowledge of CYP2D6 testing, the patients' CYP2D6 genotype was the only significant factor that predicted a change in therapy (odds ratio 22.8; 95% confidence interval 5.2 to 98.8). Genetic testing did not affect use of co-medications that interact with CYP2D6. CONCLUSIONS: CYP2D6 genotype testing led to changes in therapy among poor metabolizers, even in the absence of definitive data that an alternative medicine improved outcomes. Pharmacogenetic testing can affect choice of therapy, even in the absence of definitive data on clinical impact. PMID- 21970598 TI - Timing of oocyte retrieval and embryo transfer with pregnancy duration. AB - BACKGROUND: Recent studies have suggested that assisted reproductive technology (ART) may be associated with a shorter pregnancy duration, possibly due to various aspects of the ART procedure. The purpose of this study was to examine whether pregnancy duration is affected by timing of oocyte retrieval and embryo transfer with respect to the first day of the last menstrual period (LMP) among pregnancies achieved through in vitro fertilization with or without intracytoplasmic sperm injection. METHODS: A retrospective study was conducted at an academic center in Norfolk, Virginia, with analyses based on 294 ART cycles. RESULTS: Median and interquartile range for pregnancy duration was estimated at 38.2 +/- 3.4 weeks. Similarly, median and interquartile ranges for days between LMP and day of oocyte retrieval (27.0 +/- 2.0) and between LMP and embryo transfer (29.8 +/- 2.2) differed significantly from the standard of 14 days. Timing of oocyte retrieval and embryo transfer with respect to LMP were accelerated among multiple compared with single gestations. For single gestations, pregnancy duration was positively associated with time duration between LMP and embryo transfer (beta=0.14, p=0.036). The number of days between oocyte retrieval and embryo transfer was marginally associated with a shorter pregnancy duration in women with multiple gestations (beta=3.70, p=0.083). Controlling for patient characteristics, timing of oocyte retrieval and embryo transfer were not significantly associated with pregnancy duration. CONCLUSIONS: With few exceptions, timing of oocyte retrieval or embryo transfer did not affect pregnancy duration among ART-conceived live births. PMID- 21970599 TI - Sildenafil improves epicenter vascular perfusion but not hindlimb functional recovery after contusive spinal cord injury in mice. AB - Nitric oxide (NO) is an important regulator of vasodilation and angiogenesis in the central nervous system (CNS). Signaling initiated by the membrane receptor CD47 antagonizes vasodilation and angiogenesis by inhibiting synthesis of cyclic guanosine monophosphate (cGMP). We recently found that deletion of CD47 led to significant functional locomotor improvements, enhanced angiogenesis, and increased epicenter microvascular perfusion in mice after moderate contusive spinal cord injury (SCI). We tested the hypothesis that improving NO/cGMP signaling within the spinal cord immediately after injury would increase microvascular perfusion, angiogenesis, and functional recovery, with an acute, 7 day administration of the cGMP phosphodiesterase 5 (PDE5) inhibitor sildenafil. PDE5 expression is localized within spinal cord microvascular endothelial cells and smooth muscle cells. While PDE5 antagonism has been shown to increase angiogenesis in a rat embolic stroke model, sildenafil had no significant effect on angiogenesis at 7 days post-injury after murine contusive SCI. Sildenafil treatment increased cGMP concentrations within the spinal cord and improved epicenter microvascular perfusion. Basso Mouse Scale (BMS) and Treadscan analyses revealed that sildenafil treatment had no functional consequence on hindlimb locomotor recovery. These data support the hypothesis that acutely improving microvascular perfusion within the injury epicenter by itself is an insufficient strategy for improving functional deficits following contusive SCI. PMID- 21970600 TI - The influence of obesity on androstenedione to testosterone ratio in women with polycystic ovary syndrome (PCOS) and hyperandrogenemia. AB - The aim of the present study was to evaluate the impact of obesity and insulin resistance on testosterone formation from androstenedione and its contribution to biochemical hyperandrogenemia in all different phenotypic subgroups of PCOS patients. The case-control study included 1087 PCOS women and 206 regularly menstruating, ovulatory controls. The main clinical measurements included anthropometric and basal hormonal characteristics and evaluation of hyperandrogenic and insulin resistance-related features. The results were the following: In PCOS women with biochemical hyperandrogenemia, obesity significantly lowers serum A levels and increases T to A ratio. These findings were not present in PCOS women with clinical hypeandrogenemia and in normal ovulatory controls. PMID- 21970601 TI - Adenovirus-mediated siRNA targeting Bcl-xL inhibits proliferation, reduces invasion and enhances radiosensitivity of human colorectal cancer cells. AB - INTRODUCTION: Bcl-xL, an important member of anti-apoptotic Bcl-2 family, plays critical roles in tumor progression and development. Previously, we have reported that overexpression of Bcl-xL was correlated with prognosis of colorectal cancer (CRC) patients. The aim of this study was to investigate the association of Bcl xL expression with invasion and radiosensitivity of human CRC cells. METHODS: RT PCR and Western blot assays were performed to determine the expression of Bcl-xL mRNA and protein in CRC cells and normal human intestinal epithelial cell line. Then, adenovirus-mediated RNA interference technique was employed to inhibit the expression of Bcl-xL gene in CRC cells. The proliferation of CRC cells was analyzed by MTT and colony formation assay. The migration and invasion of CRC cells was determined by wound-healing and tranwell invasion assays. Additionally, the in vitro and in vivo radiosensitivity of CRC cells was determined by clonogenic cell survival assay and murine xnograft model, respectively. RESULTS: The levels of Bcl-xL mRNA and protein expression were significantly higher in human CRC cells than in normal human intestinal epithelial cell line. Ad/shBcl-xL could significantly reduce the expression of Bcl-xL protein in CRC cells. Also, we showed that adenovirus-mediated siRNA targeting Bcl-xL could significantly inhibit proliferation and colony formation of CRC cells. Ad/shBcl-xL could significantly suppress migration and invasion of CRC cells. Moreover, Ad/shBcl-xL could enhance in vitro and in vivo radiosensitivity of CRC cells by increasing caspase-dependent apoptosis. CONCLUSIONS: Targeting Bcl-xL will be a promising strategy to inhibit the metastatic potential and reverse the radioresistance of human CRC. PMID- 21970610 TI - Cystic mucinous adenocarcinoma of the lung: a case report. AB - Mucinous cystic tumors of the lung are uncommon, the preoperative pathologic diagnosis is difficult and their biological behavior is still controversial. We report the case of a patient with a clinically benign cystic lesion that post operatively showed to be consistent with an invasive adenocarcinoma arising in a mucinous cystadenoma of the lung. We underline the difficulty of the clinical pre operative diagnosis of this cystic neoplasia radiologically mimicking a hydatid cyst, and we report the negative TTF1 immunostaining potentially misleading in the differential diagnosis with metastatic mucinous carcinomas. Finallly, we evidence the presence of a pre-existing mucinous benign lesion suggesting early and complete resection of benign appearing lung cysts because they can undergo malignant transformation if left untreated or they can already harbor foci of invasive carcinoma at the time of the presentation. Even if a good prognosis, better than in other lung carcinomas, with no recurrrence or metastasis after complete surgical exicision, has been reported for cystic mucinous cystoadenocarcinomas, the follow-up showed an aggressive biological behaviour, with the early onset of metastasis, in keeping with P53 positive immunostaining and high Ki-67 proliferation index. PMID- 21970612 TI - Improved retroviral suicide gene transfer in colon cancer cell lines after cell synchronization with methotrexate. AB - BACKGROUND: Cancer gene therapy by retroviral vectors is mainly limited by the level of transduction. Retroviral gene transfer requires target cell division. Cell synchronization, obtained by drugs inducing a reversible inhibition of DNA synthesis, could therefore be proposed to precondition target cells to retroviral gene transfer. We tested whether drug-mediated cell synchronization could enhance the transfer efficiency of a retroviral-mediated gene encoding herpes simplex virus thymidine kinase (HSV-tk) in two colon cancer cell lines, DHDK12 and HT29. METHODS: Synchronization was induced by methotrexate (MTX), aracytin (ara-C) or aphidicolin. Gene transfer efficiency was assessed by the level of HSV-TK expression. Transduced cells were driven by ganciclovir (GCV) towards apoptosis that was assessed using annexin V labeling by quantitative flow cytometry. RESULTS: DHDK12 and HT29 cells were synchronized in S phase with MTX but not ara C or aphidicolin. In synchronized DHDK12 and HT29 cells, the HSV-TK transduction rates were 2 and 1.5-fold higher than those obtained in control cells, respectively. Furthermore, the rate of apoptosis was increased two-fold in MTX treated DHDK12 cells after treatment with GCV. CONCLUSIONS: Our findings indicate that MTX-mediated synchronization of target cells allowed a significant improvement of retroviral HSV-tk gene transfer, resulting in an increased cell apoptosis in response to GCV. Pharmacological control of cell cycle may thus be a useful strategy to optimize the efficiency of retroviral-mediated cancer gene therapy. PMID- 21970614 TI - Strategy and its implications of protein bioanalysis utilizing high-resolution mass spectrometric detection of intact protein. AB - Currently, mass spectrometry-based protein bioanalysis is primarily achieved through monitoring the representative peptide(s) resulting from analyte protein digestion. However, this approach is often incapable of differentiating the measurement of protein analyte from its post-translational modifications (PTMs) and/or potential biotransformation (BTX) products. This disadvantage can be overcome by direct measurement of the intact protein analytes. Selected reaction monitoring (SRM) on triple quadrupole mass spectrometers has been used for the direct measurement of intact protein. However, the fragmentation efficiency though the SRM process could be limited in many cases, especially for high molecular weight proteins. In this study, we present a new strategy of intact protein bioanalysis by high-resolution (HR) full scan mass spectrometry using human lysozyme as a model protein. An HR linear ion-trap/Orbitrap mass spectrometer was used for detection. A composite of isotopic peaks from one or multiple charge states can be isolated from the background and used to improve the signal-to-noise ratio. The acquired data were processed by summing extracted ion chromatograms (EIC) of the 10 most intense isotopic ions of octuply protonated lysozyme. Quantitation of the plasma lysozyme was conducted by utilizing high resolving power and an EIC window fitting to the protein molecular weight. An assay with a linear dynamic range from 0.5 to 500 MUg/mL was developed with good accuracy and precision. The assay was successfully employed for monitoring the level of endogenous lysozyme and a potential PTM in human plasma. The current instrumentation limitations and potential advantages of this approach for the bioanalysis of large proteins are discussed. PMID- 21970613 TI - In search of the genetic footprints of Sumerians: a survey of Y-chromosome and mtDNA variation in the Marsh Arabs of Iraq. AB - BACKGROUND: For millennia, the southern part of the Mesopotamia has been a wetland region generated by the Tigris and Euphrates rivers before flowing into the Gulf. This area has been occupied by human communities since ancient times and the present-day inhabitants, the Marsh Arabs, are considered the population with the strongest link to ancient Sumerians. Popular tradition, however, considers the Marsh Arabs as a foreign group, of unknown origin, which arrived in the marshlands when the rearing of water buffalo was introduced to the region. RESULTS: To shed some light on the paternal and maternal origin of this population, Y chromosome and mitochondrial DNA (mtDNA) variation was surveyed in 143 Marsh Arabs and in a large sample of Iraqi controls. Analyses of the haplogroups and sub-haplogroups observed in the Marsh Arabs revealed a prevalent autochthonous Middle Eastern component for both male and female gene pools, with weak South-West Asian and African contributions, more evident in mtDNA. A higher male than female homogeneity is characteristic of the Marsh Arab gene pool, likely due to a strong male genetic drift determined by socio-cultural factors (patrilocality, polygamy, unequal male and female migration rates). CONCLUSIONS: Evidence of genetic stratification ascribable to the Sumerian development was provided by the Y-chromosome data where the J1-Page08 branch reveals a local expansion, almost contemporary with the Sumerian City State period that characterized Southern Mesopotamia. On the other hand, a more ancient background shared with Northern Mesopotamia is revealed by the less represented Y-chromosome lineage J1-M267*. Overall our results indicate that the introduction of water buffalo breeding and rice farming, most likely from the Indian sub-continent, only marginally affected the gene pool of autochthonous people of the region. Furthermore, a prevalent Middle Eastern ancestry of the modern population of the marshes of southern Iraq implies that if the Marsh Arabs are descendants of the ancient Sumerians, also the Sumerians were most likely autochthonous and not of Indian or South Asian ancestry. PMID- 21970615 TI - The specificity of temporal expectancy: evidence from a variable foreperiod paradigm. AB - In speeded choice tasks with variable foreperiods (FPs), individuals behaviourally adapt to various frequency manipulations. Adaptations have been shown to frequencies of different stimulus-response events, to frequencies of different foreperiods, and to frequencies of different event-foreperiod combinations. We have investigated how participants adapt to a situation where all three frequency manipulations are done simultaneously. Three variable foreperiod experiments are reported. In Experiment 1, one target (the peak distributed target) appeared particularly frequently after one particular FP (the peak foreperiod), while another target was less frequent and equally distributed over all foreperiods. In Experiment 2, the equally distributed target was overall more frequent than the peak distributed one. In both experiments, performance advantages for the peak distributed target were specific to the peak foreperiod, and performance advantages at the peak foreperiod were specific to the peak distributed targets. A third experiment showed that, when two differently frequent target are both equally distributed over FPs, the performance distribution over FPs is not significantly different between both targets. Together, the results suggest that participants were able to simultaneously and specifically adapt to frequency manipulations in events, foreperiods, and event foreperiod combinations. PMID- 21970616 TI - Development of a formal catalytic asymmetric [4+2] addition of ethyl-2,3 butadienoate with acyclic enones. AB - Allene esters are unique not only as excellent electrophiles but also because of their ability for subsequent reactivity after the initial nucleophilic attack. A mechanistically inspired cyclization using ethyl-2,3-butadienoate and acyclic enones to provide dihydropyrans in excellent yields and enantioselectivity under solvent-free conditions at room temperature is reported. PMID- 21970617 TI - Tuning the electronic band structure of PCBM by electron irradiation. AB - Tuning the electronic band structures such as band-edge position and bandgap of organic semiconductors is crucial to maximize the performance of organic photovoltaic devices. We present a simple yet effective electron irradiation approach to tune the band structure of [6, 6]-phenyl-C61-butyric acid methyl ester (PCBM) that is the most widely used organic acceptor material. We have found that the lowest unoccupied molecular orbital (LUMO) level of PCBM up-shifts toward the vacuum energy level, while the highest occupied molecular orbital (HOMO) level down-shifts when PCBM is electron-irradiated. The shift of the HOMO and the LUMO levels increases as the irradiated electron fluence increases. Accordingly, the band-edge position and the bandgap of PCBM can be controlled by adjusting the electron fluence. Characterization of electron-irradiated PCBM reveals that the variation of the band structure is attributed to the molecular structural change of PCBM by electron irradiation. PMID- 21970618 TI - How well do the muscular synergies extracted via non-negative matrix factorisation explain the variation of torque at shoulder joint? AB - The way central nervous system manages the excess degrees of freedom to solve kinetic redundancy of musculoskeletal system remains an open question. In this study, we utilise the concept of synergy formation as a simplifying control strategy to find the muscle recruitment based on summation of identified muscle synergies to balance the biomechanical demands (biaxial external torque) during an isometric shoulder task. A numerical optimisation-based shoulder model was used to obtain muscle activation levels when a biaxial external isometric torque is imposed at the shoulder glenohumeral joint. In the numerical simulations, 12 different shoulder torque vectors in the transverse plane are considered. For each selected direction for the torque vector, the resulting muscle activation data are calculated. The predicted muscle activation data are used for grouping muscles in some fixed element synergies by the non-negative matrix factorisation method. Next, torque produced by these synergies are computed and projected in the 2D torque space to investigate the magnitude and direction of torques that each muscle synergy generated. The results confirmed our expectation that few dominant synergies are sufficient to reconstruct the torque vectors and each muscle contributed to more than one synergy. Decomposition of the concatenated data, combining the activation and external torque, provided functional muscle synergies that produced torques in the four principal directions. Four muscle synergies were able to account for more than 95% of variation of the original data. PMID- 21970619 TI - A Bayesian approach for determining protein side-chain rotamer conformations using unassigned NOE data. AB - A major bottleneck in protein structure determination via nuclear magnetic resonance (NMR) is the lengthy and laborious process of assigning resonances and nuclear Overhauser effect (NOE) cross peaks. Recent studies have shown that accurate backbone folds can be determined using sparse NMR data, such as residual dipolar couplings (RDCs) or backbone chemical shifts. This opens a question of whether we can also determine the accurate protein side-chain conformations using sparse or unassigned NMR data. We attack this question by using unassigned nuclear Overhauser effect spectroscopy (NOESY) data, which records the through space dipolar interactions between protons nearby in three-dimensional (3D) space. We propose a Bayesian approach with a Markov random field (MRF) model to integrate the likelihood function derived from observed experimental data, with prior information (i.e., empirical molecular mechanics energies) about the protein structures. We unify the side-chain structure prediction problem with the side-chain structure determination problem using unassigned NMR data, and apply the deterministic dead-end elimination (DEE) and A* search algorithms to provably find the global optimum solution that maximizes the posterior probability. We employ a Hausdorff-based measure to derive the likelihood of a rotamer or a pairwise rotamer interaction from unassigned NOESY data. In addition, we apply a systematic and rigorous approach to estimate the experimental noise in NMR data, which also determines the weighting factor of the data term in the scoring function derived from the Bayesian framework. We tested our approach on real NMR data of three proteins: the FF Domain 2 of human transcription elongation factor CA150 (FF2), the B1 domain of Protein G (GB1), and human ubiquitin. The promising results indicate that our algorithm can be applied in high-resolution protein structure determination. Since our approach does not require any NOE assignment, it can accelerate the NMR structure determination process. PMID- 21970620 TI - Relationship of obesity to physical activity, domestic activities, and sedentary behaviours: cross-sectional findings from a national cohort of over 70,000 Thai adults. AB - BACKGROUND: Patterns of physical activity (PA), domestic activity and sedentary behaviours are changing rapidly in Asia. Little is known about their relationship with obesity in this context. This study investigates in detail the relationship between obesity, physical activity, domestic activity and sedentary behaviours in a Thai population. METHODS: 74,981 adult students aged 20-50 from all regions of Thailand attending the Sukhothai Thammathirat Open University in 2005-2006 completed a self-administered questionnaire, including providing appropriate self reported data on height, weight and PA. We conducted cross-sectional analyses of the relationship between obesity, defined according to Asian criteria (Body Mass Index (BMI) >=25), and measures of physical activity and sedentary behaviours (exercise-related PA; leisure-related computer use and television watching ("screen-time"); housework and gardening; and sitting-time) adjusted for age, sex, income and education and compared according to a range of personal characteristics. RESULTS: Overall, 15.6% of participants were obese, with a substantially greater prevalence in men (22.4%) than women (9.9%). Inverse associations between being obese and total weekly sessions of exercise-related PA were observed in men, with a significantly weaker association seen in women (p(interaction) < 0.0001). Increasing obesity with increasing screen-time was seen in all population groups examined; there was an overall 18% (15-21%) increase in obesity with every two hours of additional daily screen-time. There were 33% (26-39%) and 33% (21-43%) reductions in the adjusted risk of being obese in men and women, respectively, reporting housework/gardening daily versus seldom or never. Exercise-related PA, screen-time and housework/gardening each had independent associations with obesity. CONCLUSIONS: Domestic activities and sedentary behaviours are important in relation to obesity in Thailand, independent of exercise-related physical activity. In this setting, programs to prevent and treat obesity through increasing general physical activity need to consider overall energy expenditure and address a wide range of low-intensity high-volume activities in order to be effective. PMID- 21970621 TI - Anti-inflammatory and anti-oxidant properties of Sida rhombifolia stems and roots in adjuvant induced arthritic rats. AB - Free radical stress leads to tissue injury and progression of disease conditions such as arthritis, hemorrhagic shock, atherosclerosis, diabetes, hepatic injury, aging and ischemia, reperfusion injury of many tissues, gastritis, tumor promotion, neurodegenerative diseases and carcinogenesis. Safer anti-oxidants suitable for long term use are needed to prevent or stop the progression of free radical mediated disorders. Herbal medicine provides a foundation for various traditional medicine systems worldwide. The Sida species is one of the most important families of medicinal plants in India. Hence, the present study was aimed to investigate the possible anti-oxidant potential of Sida rhombifolia extracts for 30 days on adjuvant induced arthritis in experimental rats. The altered levels of hematological parameters were reverted to near normal levels, especially the elevated rate of erythrocyte sedimentation was significantly reduced by S. rhombifolia extracts in experimental rats. Oral administration of root and stem of S. rhombifolia extracts significantly increased the levels of thiobarbituric acid reactive substances and activities of catalase and glutathione peroxidase and decreased the levels of reduced glutathione and superoxide dismutase activity in arthritis induced rats. The free radical scavenging activity of the plant was further evidenced by histological and transmission electron microscopy observations made on the hind limb tissue. PMID- 21970622 TI - Size-tunable hydrothermal synthesis of SnS2 nanocrystals with high performance in visible light-driven photocatalytic reduction of aqueous Cr(VI). AB - SnS(2) nanocrystals with adjustable sizes were synthesized via a hydrothermal method from the aqueous solution of common and inexpensive SnCl(4).5H(2)O, thioacetamide and citric acid, simply by varying the reaction temperature and reaction time. The structures, Brunauer-Emmett-Teller (BET) specific surface areas and optical properties of the resultant SnS(2) nanocrystals were characterized by X-ray diffraction, transmission electron microscopy, N(2) adsorption/desorption isotherms, and UV-vis diffuse reflectance spectra. Besides, their photocatalytic properties were tested for the reduction of aqueous Cr(VI) under visible light (lambda > 420 nm) irradiation. It was found that the photocatalytic activities of SnS(2) nanocrystals in aqueous suspension depended on their synthesis conditions. The product synthesized under suitable hydrothermal conditions (for example, at 150 degrees C for 12 h) not only showed high visible light-driven photocatalytic activity in the reduction of aqueous Cr(VI), but also showed good photocatalytic stability. Our photocatalytic results suggested that SnS(2) nanocrystals are a promising photocatalyst in the efficient utilization of solar energy for the treatment of Cr(VI)-containing wastewater. PMID- 21970624 TI - Simultaneous large enhancements in thermopower and electrical conductivity of bulk nanostructured half-Heusler alloys. AB - Large reductions in the thermal conductivity of thermoelectrics using nanostructures have been widely demonstrated. Some enhancements in the thermopower through nanostructuring have also been reported. However, these improvements are generally offset by large drops in the electrical conductivity due to a drastic reduction in the mobility. Here, we show that large enhancements in the thermopower and electrical conductivity of half-Heusler (HH) phases can be achieved simultaneously at high temperatures through coherent insertion of nanometer scale full-Heusler (FH) inclusions within the matrix. The enhancements in the thermopower of the HH/FH nanocomposites arise from drastic reductions in the "effective" carrier concentration around 300 K. Surprisingly, the mobility increases drastically, which compensates for the decrease in the carrier concentration and minimizes the drop in the electrical conductivity. Interestingly, the carrier concentration in HH/FH nanocomposites increases rapidly with temperature, matching that of the HH matrix at high temperatures, whereas the temperature dependence of the mobility significantly deviates from the typical T(-alpha) law and slowly decreases (linearly) with rising temperature. This remarkable interplay between the temperature dependence of the carrier concentration and mobility in the nanocomposites results in large increases in the power factor at 775 K. In addition, the embedded FH nanostructures also induce moderate reductions in the thermal conductivity leading to drastic increases in the ZT of HH(1 - x)/FH(x) nanocomposites at 775 K. By combining transmission electron microscopy and charge transport data, we propose a possible charge carrier scattering mechanism at the HH/FH interfaces leading to the observed anomalous electronic transport in the synthesized HH(1 - x)/FH(x) nanocomposites. PMID- 21970623 TI - Docosahexaenoic acid pretreatment confers protection and functional improvements after acute spinal cord injury in adult rats. AB - Currently, few interventions have been shown to successfully limit the progression of secondary damage events associated with the acute phase of spinal cord injury (SCI). Docosahexaenoic acid (DHA, C22:6 n-3) is neuroprotective when administered following SCI, but its potential as a pretreatment modality has not been addressed. This study used a novel DHA pretreatment experimental paradigm that targets acute cellular and molecular events during the first week after SCI in rats. We found that DHA pretreatment reduced functional deficits during the acute phase of injury, as shown by significant improvements in Basso-Beattie Bresnahan (BBB) locomotor scores, and the detection of transcranial magnetic motor evoked potentials (tcMMEPs) compared to vehicle-pretreated animals. We demonstrated that, at 7 days post-injury, DHA pretreatment significantly increased the percentage of white matter sparing, and resulted in axonal preservation, compared to the vehicle injections. We found a significant increase in the survival of NG2+, APC+, and NeuN+ cells in the ventrolateral funiculus (VLF), dorsal corticospinal tract (dCST), and ventral horns, respectively. Interestingly, these DHA protective effects were observed despite the lack of inhibition of inflammatory markers for monocytes/macrophages and astrocytes, ED1/OX42 and GFAP, respectively. DHA pretreatment induced levels of Akt and cyclic AMP responsive element binding protein (CREB) mRNA and protein. This study shows for the first time that DHA pretreatment ameliorates functional deficits, and increases tissue sparing and precursor cell survival. Further, our data suggest that DHA-mediated activation of pro-survival/anti-apoptotic pathways may be independent of its anti-inflammatory effects. PMID- 21970626 TI - Persistence of TEM-52/TEM-92 and SHV-12 extended-spectrum beta-lactamases in clinical isolates of Enterobacteriaceae in Italy. AB - Extended-spectrum beta-lactamases (ESBLs) belonging to the TEM and SHV families were investigated in 583 ESBL-producing Enterobacteriaceae collected at the clinical microbiology laboratories of 11 teaching Italian hospitals. By molecular analysis TEM-type and SHV-type ESBLs were confirmed on 154 and 74 isolates, respectively. High variability was found among TEM-types beta-lactamases with the following variants: TEM-5, TEM-6, TEM-12, TEM-15, TEM-24, TEM-26, TEM-29, TEM-52, TEM-92, TEM-134, and TEM-149. Among SHV variants, SHV-2a, SHV-5, SHV-12, and SHV 28 have been detected. The most widespread variants are TEM-52/92 and SHV-12. PMID- 21970625 TI - Baseline characteristics of patients with chronic kidney disease stage 3 and stage 4 in Spain: the MERENA observational cohort study. AB - BACKGROUND: To obtain information on cardiovascular morbidity, hypertension control, anemia and mineral metabolism based on the analysis of the baseline characteristics of a large cohort of Spanish patients enrolled in an ongoing prospective, observational, multicenter study of patients with stages 3 and 4 chronic kidney diseases (CKD). METHODS: Multicenter study from Spanish government hospital-based Nephrology outpatient clinics involving 1129 patients with CKD stages 3 (n = 434) and 4 (n = 695) defined by GFR calculated by the MDRD formula. Additional analysis was performed with GFR calculated using the CKD-EPI and Cockcroft-Gault formula. RESULTS: In the cohort as a whole, median age 70.9 years, morbidity from all cardiovascular disease (CVD) was very high (39.1%). In CKD stage 4, CVD prevalence was higher than in stage 3 (42.2 vs 35.6% p < 0.024). Subdividing stage 3 in 3a and 3b and after adjusting for age, CVD increased with declining GFR with the hierarchy (stage 3a < stage 3b < stage 4) when calculated by CKD-EPI (31.8, 35.4, 42.1%, p 0.039) and Cockcroft-Gault formula (30.9, 35.6, 43.4%, p 0.010) and MDRD formula (32.5, 36.2, 42.2%,) but with the latter, it did not reach statistical significance (p 0.882). Hypertension was almost universal among those with stages 3 and 4 CKD (91.2% and 94.1%, respectively) despite the use of more than 3 anti-hypertensive agents including widespread use of RAS blockers. Proteinuria (> 300 mg/day) was present in more than 60% of patients and there was no significant differences between stages 3 and 4 CKD (1.2 +/- 1.8 and 1.3 +/- 1.8 g/day, respectively). A majority of the patients had hemoglobin levels greater than 11 g/dL (91.1 and 85.5% in stages 3 and 4 CKD respectively p < 0.001) while the use of erythropoiesis-stimulating agents (ESA) was limited to 16 and 34.1% in stages 3 and 4 CKD respectively. Intact parathyroid hormone (i PTH) was elevated in stage 3 and stage 4 CKD patients (121 +/- 99 and 166 +/- 125 pg/mL p 0.001) despite good control of calcium-phosphorus levels. CONCLUSION: This study provides an overview of key clinical parameters in patients with CKD Stages 3 and 4 where delivery or care was largely by nephrologists working in a network of hospital-based clinics of the Spanish National Healthcare System. PMID- 21970627 TI - Antimicrobial susceptibility and distribution of beta-lactamase A (blaA) and beta lactamase B (blaB) genes in enteropathogenic Yersinia species. AB - One hundred eighty-six strains of enteropathogenic Yersinia (Y.) enterocolitica of bioserotypes 2/O:5,27, 2/O:9, 3/O:3, and 4/O:3 and 12 strains of Yersinia pseudotuberculosis of bioserotypes 1/O:1, 1/O:2, and 2/O:1 from different human (feces) and nonhuman (pig, pork, wild boar, monkey, chinchilla, mara, capybara, salad) sources collected in the years 1995-2009 were examined. Antimicrobial resistance patterns for 12 antimicrobial agents were generated using broth microdilution. The presence and characterization of the beta-lactamase genes blaA and blaB were studied using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP), respectively. The expression of beta lactamase BlaA and BlaB was detected using double-disc diffusion. Y. enterocolitica strains showed resistance to ampicillin (92%), streptomycin (13%), and sulfamethoxazole (2%). Intermediate susceptibility to tetracycline was shown by two Y. enterocolitica strains. All Y. pseudotuberculosis strains were susceptible to all tested antimicrobial agents. Most (99%) of the Y. enterocolitica strains carried both beta-lactamase genes. One strain of bioserotype 3/O:3 lacked both genes. In contrast, all Y. pseudotuberculosis strains carried neither of the beta-lactamase genes. Homogeneity was detected in all blaA and blaB genes of Y. enterocolitica using PCR-RFLP. The majority (89%) of Y. enterocolitica strains expressed both beta-lactamase enzymes, whereas none of the Y. pseudotuberculosis strains showed expression of either enzyme. Also, it seems that the resistance of Y. enterocolitica has not changed during the last years. PMID- 21970628 TI - Exclusion of impurity particles during grain growth in charged colloidal crystals. AB - We examine the spatial distribution of fluorescent-labeled charged polystyrene (PS) particles (particle volume fraction phi = 0.0001 and 0.001, diameter d = 183 and 333 nm) added to colloidal crystals of charged silica particles (phi = phi(s) = 0.035-0.05, d = 118 nm). At phi(s) = 0.05, the PS particles were almost randomly distributed in the volume-filling polycrystal structures before the grain growth process. Time-resolved confocal laser scanning microscopy observations reveal that the PS particles are swept to the grain boundaries of the colloidal silica crystals owing to grain boundary migration. PS particles with d = 2420 nm are not excluded from the silica crystals. We also examine influences of the impurities on the grain growth laws, such as the power law growth, size distribution, and existence of a time-independent distribution function of the scaled grain size. PMID- 21970629 TI - The effect of resident physician stress, burnout, and empathy on patient-centered communication during the long-call shift. AB - During the long-call shift medical residents experience a number of stressors that could compromise the quality of care they provide to their patients. The aim of this study was to investigate how perceived stress and burnout affect changes in empathy over the long-call shift and how those changes in empathy are associated with patient-centered communication practices. Residents (n=93) completed self-report measures of stress, burnout, and empathy at the start of their long-call shift and then completed measures of empathy and patient-centered communication at the end of the same shift. There was a significant decline in physician empathy from the beginning to the end of the long-call shift. Perceived stress was significantly associated with higher burnout, which was, in turn, significantly associated with declines in empathy from pre- to posttest. Declines in empathy predicted lower self-reported patient-centered communication during the latter half of the shift. This study suggests that residents who perceive high levels of stress are at risk for burnout and deterioration in empathy toward their patients, both of which may compromise the quality of their interactions with patients. PMID- 21970630 TI - Canonical Wnt signaling is involved in switching from cell proliferation to myogenic differentiation of mouse myoblast cells. AB - BACKGROUND: Wnt/beta-catenin signaling is involved in various aspects of skeletal muscle development and regeneration. In addition, Wnt3a and beta-catenin are required for muscle-specific gene transcription in embryonic carcinoma cells and satellite-cell proliferation during adult skeletal muscle regeneration. Downstream targets of canonical Wnt signaling are cyclin D1 and c-myc. However both target genes are suppressed during differentiation of mouse myoblast cells, C2C12. Underlying molecular mechanisms of beta-catenin signaling during myogenic differentiation remain unknown. RESULTS: Using C2C12 cells, we examined intracellular signaling and gene transcription during myoblast proliferation and differentiation. We confirmed that several Wnt signaling components, including Wnt9a, Sfrp2 and porcupine, were consistently upregulated in differentiating C2C12 cells. Troponin T-positive myotubes were decreased by Wnt3a overexpression, but not Wnt4. TOP/FOP reporter assays revealed that co-expression with Wnt4 reduced Wnt3a-induced luciferase activity, suggesting that Wnt4 signaling counteracted Wnt3a signaling in myoblasts. FH535, a small-molecule inhibitor of beta-catenin/Tcf complex formation, reduced basal beta-catenin in the cytoplasm and decreased myoblast proliferation. K252a, a protein kinase inhibitor, increased both cytosolic and membrane-bound beta-catenin and enhanced myoblast fusion. Treatments with K252a or Wnt4 resulted in increased cytoplasmic vesicles containing phosphorylated beta-catenin (Tyr654) during myogenic differentiation. CONCLUSIONS: These results suggest that various Wnt ligands control subcellular beta-catenin localization, which regulate myoblast proliferation and myotube formation. Wnt signaling via beta-catenin likely acts as a molecular switch that regulates the transition from cell proliferation to myogenic differentiation. PMID- 21970639 TI - The promoter -1031(T/C) polymorphism in tumor necrosis factor-alpha associated with polycystic ovary syndrome. AB - BACKGROUND: A tumor necrosis factor-alpha is a multifunctional pro-inflammation cytokine, which has been considered as one of pathogenic factors for various diseases. The promoter -1031(T/C) polymorphism in the tumor necrosis factor-alpha gene was reported that it plays a part in reproduction-related diseases. Among these, polycystic ovary syndrome (PCOS) is known to be a common gynecological disease of women in reproductive age women. Here, we performed a comparative study of -1031(T/C) polymorphism of TNF-alpha gene with PCOS in a Korean population. METHODS: The -1031(T/C) polymorphism of TNF-alpha gene was analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) in a total of 217 PCOS patients and 144 matched female controls of healthy women. And statistical analysis was performed using HapAnalyzer. X2 test and logistic regression were utilized analyze the association between two groups. A p-value under 0.05 was considered statistically significant. RESULTS: The genotype and allelic frequencies were in Hardy-Weinberg equilibrium (HWE). There was strong association between the -1031(T/C) polymorphism in the promoter region of TNF alpha gene and PCOS (p-value = 0.0003, odd ratio (OR) = 2.53). In addition, the frequency of C allele was significantly higher in PCOS patients compared with controls. Sequence analyses also showed the -1031(T/C) polymorphism of TNF-alpha gene. CONCLUSION: This is the first study on the -1031(T/C) polymorphism of TNF alpha gene in PCOS. We concluded that the -1031(T/C) polymorphism of TNF-alpha gene is associated with PCOS in a Korean population. Therefore, it is possible that it may be considered as a clinical biomarker to diagnose for PCOS, and is helpful in understanding the etiology for the pathogenesis of PCOS. PMID- 21970640 TI - Developing high performance lipoprotein density profiling for use in clinical studies relating to cardiovascular disease. AB - Early detection of the beginning stage of cardiovascular disease (CVD) is an approach to prevention because the process is reversible at this stage. Consequently, several methods for screening for CVD have been introduced in recent years incorporating different analytical methods for characterizing the population of blood-borne lipoprotein subclasses. The gold standard method for lipoprotein subclassification is based on lipoprotein density measured by sedimentation equilibrium using the ultracentrifuge. However, this method has not been adopted for clinical studies because of difficulties in achieving the precision required for distinguishing individuals with and without CVD particularly when statistical classification methods are used. The objective of this study was to identify and improve the major factors that influence the precision of measurement of lipoprotein density profile by sedimentation equilibrium analysis and labeling with a fluorescent probe. The study has two phases, each contributing to precision. The first phase focuses on the ultracentrifugation-related variables, and the second phase addresses those factors involved in converting the fluorescent lipoprotein density profile to a digital format compatible with statistical analysis. The overall improvement in precision was on the order of a factor of 5, sufficient to be effectively applied to ongoing classification studies relating to CVD risk assessment. PMID- 21970641 TI - Medical advances in child sexual abuse. AB - This volume is the first of a two-part special issue detailing state of the art practice in medical issues around child sexual abuse. The six articles in this issue explore methods for medical history evaluation, the rationale for when sexual examinations should take place, specific hymenal findings that suggest a child has been sexually abused, the healing of genital injuries, approaches to interpretation of medical findings, and the neurological harm of sexual abuse. From the initial history to the process of the medical examination, the mechanics of what a genital examination might show, and the neurobiological consequences, it is demonstrated that the harm of sexual abuse is has more effect on the brain than the genital area. PMID- 21970642 TI - Conducting the medical history. AB - A key portion of the medical evaluation of child sexual abuse is the medical history. This differs from interviews or histories obtained by other professionals in that it is focuses more on the health and well-being of the child. Careful questions should be asked about all aspects of the child's medical history by a skilled, compassionate, nonjudgmental, and objective clinician. Often the diagnosis of sexual abuse is based only on the medical history. The history can be further understood by knowledge of how children are abused and their reactions to it. By addressing the child's and parent's concerns, reassurance can also be provided about what is normal and abnormal with the child's body. PMID- 21970643 TI - Timing of the medical examination. AB - The medical examination of the sexually abused child may have evidentiary, medical, and therapeutic purposes, and the timing of the examination requires consideration of each of these objectives. In cases of acute sexual assault, emergent examinations may be needed to identify injury, collect forensic evidence, and provide infection and pregnancy prophylaxis. Alternately, most sexually abused children are not identified immediately after assault, and the timing of the examination needs to balance physical and emotional issues with the availability of qualified examiners. In all cases, the best interests of the child should be paramount. PMID- 21970644 TI - Hymenal characteristics in girls with and without a history of sexual abuse. AB - This article reviews the recent literature on physical findings related to the hymen in pubertal and prepubertal girls with and without a history of sexual abuse. Characteristics of normal hymenal anatomy, acute traumatic findings, and characteristics of healed trauma are discussed, particularly with regard to changes in the interpretation of these findings that have occurred over time. PMID- 21970645 TI - Healing of genital injuries. AB - Child sexual abuse as well as accidental trauma may cause acute injuries in the anogenital area. Most data on residual findings following genital trauma come from longitudinal studies of children who have been sexually assaulted, undergone surgical procedures, or experienced accidental trauma. Like injuries in other part parts of the body, such injuries undergo a predictable pattern of healing. Most superficial injuries heal without any residual evidence. Deeper injuries, as well as those that become infected or experience repeated disruption, may produce permanent changes. While the presence of such changes supports allegations of prior anogenital trauma, their absence does not preclude the trauma from having occurred. PMID- 21970647 TI - Medical evaluation of suspected child sexual abuse: 2011 update. AB - The medical evaluation of children with suspected sexual abuse includes more than just the physical examination of the child. The importance of taking a detailed medical history from the parents and a history from the child about physical sensations following sexual contact has been emphasized in other articles in the medical literature. The examination is important, however, and medical providers who examine children need to be aware of published research on findings in nonabused children, studies of healing of injuries, and studies documenting the association between sexual contact and the diagnosis of sexually transmissible infections in children. This article reviews the current approach to interpreting findings in children who may have been sexually abused and why additional research is needed. PMID- 21970648 TI - Ortho2ExpressMatrix--a web server that interprets cross-species gene expression data by gene family information. AB - BACKGROUND: The study of gene families is pivotal for the understanding of gene evolution across different organisms and such phylogenetic background is often used to infer biochemical functions of genes. Modern high-throughput experiments offer the possibility to analyze the entire transcriptome of an organism; however, it is often difficult to deduct functional information from that data. RESULTS: To improve functional interpretation of gene expression we introduce Ortho2ExpressMatrix, a novel tool that integrates complex gene family information, computed from sequence similarity, with comparative gene expression profiles of two pre-selected biological objects: gene families are displayed with two-dimensional matrices. Parameters of the tool are object type (two organisms, two individuals, two tissues, etc.), type of computational gene family inference, experimental meta-data, microarray platform, gene annotation level and genome build. Family information in Ortho2ExpressMatrix bases on computationally different protein family approaches such as EnsemblCompara, InParanoid, SYSTERS and Ensembl Family. Currently, respective all-against-all associations are available for five species: human, mouse, worm, fruit fly and yeast. Additionally, microRNA expression can be examined with respect to miRBase or TargetScan families. The visualization, which is typical for Ortho2ExpressMatrix, is performed as matrix view that displays functional traits of genes (differential expression) as well as sequence similarity of protein family members (BLAST e-values) in colour codes. Such translations are intended to facilitate the user's perception of the research object. CONCLUSIONS: Ortho2ExpressMatrix integrates gene family information with genome-wide expression data in order to enhance functional interpretation of high-throughput analyses on diseases, environmental factors, or genetic modification or compound treatment experiments. The tool explores differential gene expression in the light of orthology, paralogy and structure of gene families up to the point of ambiguity analyses. Results can be used for filtering and prioritization in functional genomic, biomedical and systems biology applications. The web server is freely accessible at http://bioinf-data.charite.de/o2em/cgi-bin/o2em.pl. PMID- 21970646 TI - Neurodevelopmental biology associated with childhood sexual abuse. AB - Child maltreatment appears to be the single most preventable cause of mental illness and behavioral dysfunction in the United States. Few published studies examine the developmental and the psychobiological consequences of sexual abuse. There are multiple mechanisms through which sexual abuse can cause post-traumatic stress disorder, activate biological stress response systems, and contribute to adverse brain development. This article will critically review the psychiatric problems associated with maltreatment and the emerging biologic stress system research with a special emphasis on what is known about victimization by sexual abuse. PMID- 21970650 TI - Mental representations of arithmetic facts: evidence from eye movement recordings supports the preferred operand-order-specific representation hypothesis. AB - There are three main hypotheses about mental representations of arithmetic facts: the independent representation hypothesis, the operand-order-free single representation hypothesis, and the operand-order-specific single-representation hypothesis. The current study used electrical recordings of eye movements to examine the organization of arithmetic facts in long-term memory. Subjects were presented single-digit addition and multiplication problems and were asked to report the solutions. Analyses of the horizontal electrooculograph (HEOG) showed an operand order effect for multiplication in the time windows 150-300 ms (larger negative potentials for smaller operand first problems than for larger operand first ones). The operand order effect was reversed in the time windows from 400 to 1,000 ms (i.e., larger operand first problems had larger negative potentials than smaller operand first problems). For addition, larger operand first problems had larger negative potentials than smaller operand first in the series of time windows from 300 to 1,000 ms, but the effect was smaller than that for multiplication. These results confirmed the dissociated representation of addition and multiplication facts and were consistent with the prediction of the preferred operand-order-specific representation hypothesis. PMID- 21970649 TI - Hypersensitivity reactions to anticancer agents: data mining of the public version of the FDA adverse event reporting system, AERS. AB - BACKGROUND: Previously, adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) database were reviewed to confirm platinum agent associated hypersensitivity reactions. The present study was performed to confirm whether the database could suggest the hypersensitivity reactions caused by anticancer agents, paclitaxel, docetaxel, procarbazine, asparaginase, teniposide, and etoposide. METHODS: After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving candidate agents were analyzed. The National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 was applied to evaluate the susceptibility to hypersensitivity reactions, and standardized official pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. RESULTS: Based on 1,644,220 AERs from 2004 to 2009, the signals were detected for paclitaxel-associated mild, severe, and lethal hypersensitivity reactions, and docetaxel-associated lethal reactions. However, the total number of adverse events occurring with procarbazine, asparaginase, teniposide, or etoposide was not large enough to detect signals. CONCLUSIONS: The FDA's adverse event reporting system, AERS, and the data mining methods used herein are useful for confirming drug-associated adverse events, but the number of co-occurrences is an important factor in signal detection. PMID- 21970651 TI - Effect of five-membered heteroaromatic linkers to the performance of phenothiazine-based dye-sensitized solar cells. AB - Phenothiazine derivatives with various conjugated linkers (furan, thiophene, and 3,4-ethylenedioxythiophene) were synthesized and used in dye-sensitized solar cells to study the effect of conjugated linkers on device performance. Among them, one with furan as a conjugated linker showed a solar energy-to-electricity conversion efficiency (eta) of 6.58%, an improvement of over 24% compared with the T2-1 reference cells' 5.29% under AM 1.5 G irradiation. PMID- 21970652 TI - Monte Carlo studies of the XY model on two-dimensional curved surfaces. AB - To explore the interaction between topological defects and curvature in materials with orientational order, we perform Monte Carlo studies of the two-dimensional XY model on the surface of curved substrates. Each curved surface is patterned with a random lattice constructed via random sequential absorption, and an XY spin is positioned at each lattice site. Spins lie in the plane locally tangent to the surface and interact with neighbors defined via a distance cutoff. We demonstrate that the relative phase associated with vortices is significant in curved geometries and plays a role in microstructural evolution. We also observe that any nonuniform curvature, e.g., on the surface of a torus, induces spontaneous segregation of positive and negative vortices and promotes the formation of deeply metastable defect microstructures. Though qualitative in nature, these observations provide novel insights into the patterning of topological defects in curved geometries and suggest that the Kosterlitz-Thouless transition may be altered in geometries with nonuniform curvature. PMID- 21970653 TI - Hierarchically controlled helical graphite films prepared from iodine-doped helical polyacetylene films using morphology-retaining carbonization. AB - One-handed helical graphite films with a hierarchically controlled morphology were prepared from iodine-doped helical polyacetylene (H-PA) films using the recently developed morphology-retaining carbonization method. Results from scanning electron microscopy indicate that the hierarchical helical morphology of the H-PA film remains unchanged even after carbonization at 800 degrees C. The weight loss of the film due to carbonization was very small; only 10-29% of the weight of the film before doping was lost. Furthermore, the graphite film prepared by subsequent heating at 2600 degrees C retained the same morphology as that of the original H-PA film and that of the helical carbon film prepared at 800 degrees C. The screwed direction, twisted degree, and vertical or horizontal alignment of the helical graphite film were well controlled by changing the helical sense, helical pitch, and orientation state of the chiral nematic liquid crystal (N*-LC) used as an asymmetric LC reaction field. X-ray diffraction and Raman scattering measurements showed that graphitic crystallization proceeds in the carbon film during heat treatment at 2600 degrees C. Transmission electron microscopy measurements indicate that ultrasonication of the helical graphite film in ethanol for several hours gives rise to a single helical graphite fibril. The profound potentiality of the present graphite films is exemplified in their electrical properties. The horizontally aligned helical graphite film exhibits an enhancement in electrical conductivity and an evolution of electrical anisotropy in which conductivity parallel to the helical axis of the fibril bundle is higher than that perpendicular to the axis. PMID- 21970654 TI - Controllable synthesis of flake-like Al-doped ZnO nanostructures and its application in inverted organic solar cells. AB - Flake-like Al-doped ZnO (AZO) nanostructures including dense AZO nanorods were obtained via a low-temperature (100 degrees C) hydrothermal process. By doping and varying Al concentrations, the electrical conductivity (sigma) and morphology of the AZO nanostructures can be readily controlled. The effect of sigma and morphology of the AZO nanostructures on the performance of the inverted organic solar cells (IOSCs) was studied. It presents that the optimized power conversion efficiency of the AZO-based IOSCs is improved by approximately 58.7% compared with that of un-doped ZnO-based IOSCs. This is attributed to that the flake-like AZO nanostructures of high sigma and tunable morphology not only provide a high conduction pathway to facilitate electron transport but also lead to a large interfacial area for exciton dissociation and charge collection by electrodes. PMID- 21970655 TI - Long circulating PEGylated PLGA nanoparticles of cytarabine for targeting leukemia. AB - The present investigation was aimed at developing PEGylated PLGA nanoparticles of cytarabine. PLGA Nanoparticles were prepared by modified nanoprecipitation method, optimized for mean particle size (152 +/- 6 nm) and entrapment efficiency (41.1 +/- 0.8%) by a 32 factorial design. The PEGylated PLGA nanoparticles of cytarabine had a zeta potential of -7.5 +/- 1.3 mV and sustained the release of cytarabine for 48 h by Fickian diffusion. The IC50 values for L1210 cells were 6.5, 5.3, and 2.2 uM for cytarabine, cytarabine loaded PLGA nanoparticles and cytarabine loaded PLGA-mPEG nanoparticles respectively. Confocal microscopy and flow cytometry showed that the nanoparticles were internalized by the L1210 cells and not simply bound to their surface. Biodistribution studies showed that the PEGylated nanoparticles of cytarabine were present in significantly higher concentrations in blood circulation as well as in brain and bones and avoided RES uptake as compared to the free drug. PMID- 21970656 TI - Preparation and evaluation of easy energy supply property of medium-chain fatty acids liposomes. AB - To develop an easy-energy-supply agent, medium-chain fatty acids (MCFAs) liposomes were prepared by thin-layer dispersion, freeze-thawing and dynamic high pressure microfluidization (DHPM)-freeze-thawing methods. Results showed that MCFAs nanoliposomes obtained by the novel method (DHPM-freeze-thawing) exhibited a smaller size (72.6 +/- 4.9 nm), narrower size distribution (PDI = 0.175 +/- 0.005), higher zeta potential (-41.27 +/- 1.16 mV) and entrapment efficiency (45.9 +/- 6.0%) compared to the other two methods. In the weight-loaded swimming test of the mice, the high-dose group of MCFAs nanoliposomes indicated a significantly longer swimming time (105 +/- 31 min, p < 0.05), a lower serum urea nitrogen (839.5 +/- 111.9 mg/L, p < 0.05) and blood lactic acid (5.7 +/- 1.0 mmol/L, p <= 0.001), and a higher hepatic glycogen (15.0 +/- 3.6 mg/g, p <= 0.001) than those of the control group (53 +/- 13 min, 1153.6 +/- 102.5 mg/L, 12.5 +/- 1.9 mmol/L and 8.8 +/- 3.3 mg/g, respectively). However, no significant difference was found between the high-dose group and MCFAs group. The results suggested that MCFAs nanoliposomes could be used as a potential easy-energy supply agent. PMID- 21970657 TI - Biofunctional textiles prepared with liposomes: in vivo and in vitro assessment. AB - A sun filter, ethyl hexyl methoxycinnamate (EHMC) used as a tracer, was vehiculized by liposomes made up of internal wool lipids (IWL) or phosphatidylcholine (PC) and applied onto cotton and polyamide fabrics by exhaustion treatments. After topical applications of textiles on human volunteers, skin properties were evaluated by non-invasive biophysical techniques. Two methodologies based on percutaneous absorption were used to determine the content of the active principle penetration into the skin. PC liposomes showed more affinity for the fabric than IWL liposomes. Moreover, polyamide fabrics absorbed a slightly higher percentage of liposomes than cotton fabrics. A significantly higher amount of EHMC skin penetration was found when the biofunctional textiles were topically applied than when formulations were applied onto the skin. Moreover, the polyamide was the fibre with the highest released properties in all cases. PMID- 21970658 TI - Biofriendly bonding processes for nanoporous implantable SU-8 microcapsules for encapsulated cell therapy. AB - Mechanically robust, cell encapsulating microdevices fabricated using photolithographic methods can lead to more efficient immunoisolation in comparison to cell encapsulating hydrogels. There is a need to develop adhesive bonding methods which can seal such microdevices under physiologically friendly conditions. We report the bonding of SU-8 based substrates through (i) magnetic self assembly, (ii) using medical grade photocured adhesive and (iii) moisture and photochemical cured polymerization. Magnetic self-assembly, carried out in biofriendly aqueous buffers, provides weak bonding not suitable for long term applications. Moisture cured bonding of covalently modified SU-8 substrates, based on silanol condensation, resulted in weak and inconsistent bonding. Photocured bonding using a medical grade adhesive and of acrylate modified substrates provided stable bonding. Of the methods evaluated, photocured adhesion provided the strongest and most stable adhesion. PMID- 21970659 TI - An indirect comparison of the efficacy of bevacizumab plus carboplatin and paclitaxel versus pemetrexed with cisplatin in patients with advanced or recurrent non-squamous adenocarcinoma non-small cell lung cancer. AB - OBJECTIVE: There are two new treatment options available for the treatment of adenocarcinoma histology non-small cell lung cancer (NSCLC) which offer improved benefit in terms of progression-free (PFS) and overall survival (OS) over chemotherapy. Both bevacizumab and pemetrexed when combined with chemotherapy significantly increase PFS and OS in patients with advanced NSCLC versus chemotherapy alone. The aim of this analysis was to compare the efficacy for patients with non-squamous adenocarcinoma NSCLC treated with bevacizumab, carboplatin and paclitaxel (BCP) to pemetrexed and cisplatin (PC) by using indirect comparison (ITC) methodology. EXPERIMENTAL DESIGN: In the absence of head-to-head trials, ITC was performed on patients with adenocarcinoma histology non-squamous NSCLC to compare the relative benefit of first-line therapies BCP vs. PC by hazard ratios (HR). Subsequently, these HRs were used in a decision analytic Markov model with a lifelong time horizon to extrapolate the long-term effectiveness of the two treatments. RESULTS: ITC estimated HRs for the primary endpoints in the bevacizumab study E4599 showed that BCP treatment in non squamous adenocarcinoma NSCLC patients resulted in a BCP HR of 0.82 versus PC. The long-term predictions from the Markov model yielded a mean survival of 1.48 years (95% CI 1.34, 1.62 years) (or 17.7 months) for BCP compared with 1.29 years (95% CI 1.16, 1.42 years) (or 15.4 months) for PC. CONCLUSIONS: Based on our decision analysis, triplet BCP targeted therapy in patients with advanced non squamous adenocarcinoma NSCLC compared with doublet PC chemotherapy results in improved expected values for overall long-term survival. Therefore, from the efficacy perspective, bevacizumab in combination with platinum-based chemotherapy can be considered as the targeted therapy of choice for patients with advanced non-squamous adenocarcinoma NSCLC. PMID- 21970660 TI - Relative bioavailability of a 5 mg mosapride/10 mg rabeprazole fixed dose combination tablet versus separate single tablets in healthy volunteers: a single dose randomized open-label crossover study. AB - OBJECTIVE: To evaluate the relative bioavailability of a new formulation containing 5 mg mosapride and 10 mg rabeprazole (T) and compare it with the branded formulations of both drugs co-administered in separate tablets (R) to meet the regulatory requirements of bioequivalence in Argentina. METHODS: A randomized-sequence, open-label, two-period crossover study was conducted on 24 healthy Caucasian volunteers in a fasting state. A single oral dose of either T or R formulations was followed by a 7-day washout period. Blood samples for mosapride were collected before administration (baseline) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, and 24 h after administration. Samples for rabeprazole were taken baseline and at 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8 and 10 h after dosing. Mosapride and rabeprazole concentrations were determined using a validated LC-MS/MS method. Adverse events were monitored based on clinical parameters and volunteer reports. RESULTS: The geometric means (90% CI) C(max) for mosapride in T and R were 23.13 (20.05-39.45) and 23.09 (21.69-32.37) ng/mL, the AUC(0-)(t) were 70.80 (66.23-102.37) and 70.81 (66.35-93.26) ng h/mL and the AUC(0-infinity) were 74.05 (69.29-106.11) and 74.98 (70.43-97.77) ng h/mL. For rabeprazole T and R the C(max) were 197.42 (186.12-239.91) and 195.50 (186.08 250.07) ng/mL, the AUC(0-)(t) were 294.90 (275.13-374.15) and 296.96 (280.11 387.89) ng h/mL and the AUC(0-infinity) were 301.12 (280.78-380.82) and 304.07 (286.60-394.21), respectively. No differences were detected between the formulations. The T/R ratios (90% CI) for C(max), AUC(0-)(t) and AUC(0-infinity) were 100.17% (82.35-121.84), 99.99% (87.58-114.16) and 98.77% (87.02-112.11) for mosapride, and 100.99% (85.14-119.77), 99.31% (84.74-116.38) and 99.03% (85.07 115.28) for rabeprazole. No subject complained of adverse events. CONCLUSIONS: In this single-dose study, the mosapride/rabeprazole tablets (test formulation) met the criterion for bioequivalence with the reference formulations. Study limitations include single-dose, open-label design, and a small sample of healthy volunteers. PMID- 21970661 TI - Review of the series "Disease of the year 2011: toxoplasmosis" pathophysiology of toxoplasmosis. AB - Toxoplasma gondii is a major cause of chronic parasitic infection in the world. This protozoan can cause retino-choroiditis in newborns and in adults, both immunocompetent and immunodeficient. This disease tends to be recurrent and can lead to severe visual impairment. The authors review current knowledge on the role of parasite genetics in influencing susceptibility to ocular toxoplasmosis and on the immuno-pathogenesis of this disease. PMID- 21970662 TI - Therapy for ocular toxoplasmosis. AB - PURPOSE: To review current evidence for the treatment of ocular toxoplasmosis (OT). DESIGN: Narrative review and expert recommendations. METHODS: Meta-analysis and selected original articles from the medical literature were reviewed critically. Expert recommendations were analyzed. RESULTS: Numerous observational studies suggest a benefit of short-term antimicrobial therapy for toxoplasmic retinochoroiditis in immunocompetent patients, although its efficacy has not been proven in randomized clinical trials. A randomized clinical trial revealed that intermittent trimethoprim/sulfamethoxazole treatment could decrease the rate of recurrence in high-risk patients. Intravitreal injection of clindamycin and dexamethasone was an acceptable alternative to the classic treatment for OT in a randomized clinical trial. CONCLUSIONS: Opinions about therapy differ and controversy remains about its type, efficacy, and length. Intravitreal therapy may be promising for OT. A recent description of the presence of parasitemia in patients with active and inactive ocular toxoplasmosis raises new questions that need to be explored. PMID- 21970663 TI - Intermediate uveitis in a pediatric Italian population. AB - PURPOSE: To investigate clinical data, outcome, and treatment of intermediate uveitis in children. METHODS: Retrospective cohort study, including 116 children affected by intermediate uveitis. RESULTS: Sixty-two percent of patients were males. Ocular involvement was bilateral in 84%. Mean age at uveitis onset was 10.3 +/- 3.6 years and 12.2 +/- 7 years at first visit. Ninety-seven percent were classified as having idiopathic uveitis. The incidence of ocular complications during follow-up was 0.131/eye-year. Macular edema or a marked vitreous haze at presentation may be risks factors for incident visual loss. The most frequent causes of visual loss were macular edema (64%) and cataract (21%). CONCLUSIONS: Most cases are idiopathic (pars planitis); only few children presented associated systemic disease. Macular edema and severe vitritis at presentation are associated with increased risk of visual impairment. Cystoid macular edema is the main cause of visual impairment. PMID- 21970664 TI - Intraocular parasitic infections. AB - A parasite is a living organism that receives some of its basic nutritional requirements through intimate contact with another living organism. When the parasite reaches the eye, ocular complications occur due to mechanical, immunologic, or allergic reactions. When an ophthalmologist detects a parasite in the eye, it is often difficult to identify the exact organism. Lack of methodological uniformity in management of ocular parasitosis emphasizes the need for standardization, including construction of a management algorithm. Knowledge on immunoreactivity in systemic parasitology has grown remarkably, but translational research from bench to bedside needs to be improved. Newer molecular diagnostic techniques are essential for ophthalmic application. Many parasitic worms are developing resistance to available drugs, necessitating discovery of the next generation of anti-parasitic agents. The aim of this review is to understand the existing literature on ocular parasitosis, to highlight diagnostic and therapeutic advances, and to analyze the management algorithm on ocular parasitosis. PMID- 21970665 TI - Lupus relapse presented as frosted branch retinal angiitis: case report. AB - PURPOSE: To describe a systemic lupus erythematosus (SLE) relapse, which presented as frosted branch retinal angiitis. DESIGN: Clinical case report. METHODS: A 16-year-old female patient had an SLE relapse that appeared as frosted branch angiitis while being treated with deflazacort and azathioprine. RESULTS: Complete resolution of the vasculitis was achieved with a 3-day course of pulsed intravenous methylprednisolone and oral prednisone 3 weeks later. CONCLUSIONS: Even with proper immunosuppressive treatment, SLE can relapse. This case presented as frosted branch retinal angiitis, which is a clinical picture that is rarely described in SLE. PMID- 21970666 TI - Ocular pulse amplitude in Behcet disease. PMID- 21970667 TI - Plasma exchange and rituximab in the management of acute occlusive retinal vasculopathy secondary to systemic lupus erythematosus. AB - PURPOSE: To report a case of acute occlusive retinal vasculopathy secondary to systemic lupus erythematosus (SLE) successfully treated with plasma exchange and rituximab METHODS: Case report. RESULTS: A 25-year-old female presenting acutely with lupus retinal vasculitis was treated urgently with plasma exchange after failure to respond to intravenous methylprednisolone. Following this, fluorescein angiography demonstrated reperfusion of occluded arterioles. Visual acuity improved from 6/60 to 6/6 bilaterally. Remission was maintained following rituximab (Rituxan) in combination with mycophenolatemofetil and oral prednisolone. CONCLUSIONS: Early treatment with plasma exchange achieved reperfusion of the occluded microvascular circulation with correspondingly good visual recovery and should be considered when patients present with corticosteroid refractory retinal vasculitis associated with SLE. PMID- 21970668 TI - Efficacy of tocilizumab in two patients with anti-TNF-alpha refractory uveitis. AB - PURPOSE: To report on two patients with refractory uveitis treated with tocilizumab; a new humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). DESIGN: Retrospective interventional case series. METHODS: Both patients received a monthly infusion of tocilizumab 8 mg/kg; associated with corticosteroids. Outcome measures were visual acuity and central retinal thickness evaluated with optical coherence tomography. RESULTS: An improvement in visual acuity and a decrease in macular edema were observed in these two patients. CONCLUSIONS: Tocilizumab seems to be a promising treatment in refractory uveitis. A prospective study is needed to evaluate the role of this new agent in the management of refractory uveitis. PMID- 21970670 TI - Interaction of microstructure and microcrack growth in cortical bone: a finite element study. AB - Microstructural features including osteons and cement lines are considered to play an important role in determining the crack growth behaviour in cortical bone. This study aims to develop a computational mechanics approach to evaluate microscale fracture mechanisms in bone. In this study, finite element models based on actual human cortical bone images that allow for arbitrary crack growth were utilised to determine the crack propagation behaviour. The simulations varied the cement line and osteon strength and fracture toughness in different bone microstructures to assess the crack propagation trajectory, stress-strain relationship and nonlinear strain energy density. The findings of this study provide additional insight into the individual influence of microstructural features and their properties on crack growth behaviour in bone using a computational approach. PMID- 21970669 TI - Psychometric assessment of HIV/STI sexual risk scale among MSM: a Rasch model approach. AB - BACKGROUND: Little research has assessed the degree of severity and ordering of different types of sexual behaviors for HIV/STI infection in a measurement scale. The purpose of this study was to apply the Rasch model on psychometric assessment of an HIV/STI sexual risk scale among men who have sex with men (MSM). METHODS: A cross-sectional study using respondent driven sampling was conducted among 351 MSM in Shenzhen, China. The Rasch model was used to examine the psychometric properties of an HIV/STI sexual risk scale including nine types of sexual behaviors. RESULTS: The Rasch analysis of the nine items met the unidimensionality and local independence assumption. Although the person reliability was low at 0.35, the item reliability was high at 0.99. The fit statistics provided acceptable infit and outfit values. Item difficulty invariance analysis showed that the item estimates of the risk behavior items were invariant (within error). CONCLUSIONS: The findings suggest that the Rasch model can be utilized for measuring the level of sexual risk for HIV/STI infection as a single latent construct and for establishing the relative degree of severity of each type of sexual behavior in HIV/STI transmission and acquisition among MSM. The measurement scale provides a useful measurement tool to inform, design and evaluate behavioral interventions for HIV/STI infection among MSM. PMID- 21970671 TI - Efficacy of second-generation antihistamines in patients with allergic rhinitis and comorbid asthma. AB - BACKGROUND AND AIMS: Allergic rhinitis (AR) and asthma share common mediators, cytokines, and chemokines from mast cells and basophils that are central to the complex cascade of events involved in the inflammatory response. Histamine is the salient mediator released after immunologic challenge, initiating multiple pathologic processes of the allergic reaction that result in bronchial smooth muscle contraction, vasodilation, mucus hypersecretion, and edema. The recent identification of a fourth histamine receptor has reinforced clinical interest in the pleiotropic effects of histamine and the relative roles of histamine receptors in mediating immune and inflammatory responses. MATERIAL AND METHODS: A comprehensive literature search was conducted for the following terms, alone or in combination: allergic rhinitis, asthma, antihistamines, histamine, and histamine receptors, and for the second-generation antihistamines azelastine, cetirizine, desloratadine, ebastine, fexofenadine, levocetirizine, loratadine, mizolastine, and rupatadine. Clinical trials were included that reported results for patients with AR and comorbid asthma who were treated with second-generation antihistamines. The search dates ranged from 1995 through 2010. Clinical studies that were not placebo controlled or double blinded were excluded from this review. RESULTS: A total of 14 clinical trials of second-generation nonsedating antihistamines were included in this review. CONCLUSION: H1-antihistamines have been shown to attenuate the symptoms associated with early- and late-phase allergic reactions. Cumulative clinical evidence indicates that H1-antihistamines may have a beneficial effect on asthma symptoms and improve quality of life. Scientific significance. Mechanistic and clinical data suggest that the potential of H1-antihistamines to alleviate comorbid asthma symptoms in AR patients should be further investigated. PMID- 21970672 TI - Help a buddy take a knee: creating persuasive messages for military service members to encourage others to seek mental health help. AB - Helping service members returning from the wars in Iraq and Afghanistan who need mental health help is an important problem for the United States military. Tanielian and Jaycox (2008) estimated that approximately 14%, or 300,000, of the service members returning from the wars have posttraumatic stress disorder (PTSD), yet just over half of those needing psychological help seek it despite the availability of effective treatments. This article reports the focus group responses of military personnel about message factors associated with persuading individuals to encourage others to seek mental health help. The results have theoretical and practical implications for future message design for promoting increased usage of mental health services among members of this population. Responses are presented in terms of the communication variables of source, message, channel, and receiver factors. PMID- 21970673 TI - Unearthing potentials for decarbonizing the U.S. aluminum cycle. AB - Global aluminum demand is anticipated to triple by 2050, by which time global greenhouse gas (GHG) emissions are advised to be cut 50-85% to avoid catastrophic climate impacts. To explore mitigation strategies systematically, a dynamic material flow model was developed to simulate the stocks and flows of the U.S. aluminum cycle and analyze the corresponding GHG emissions. Theoretical and realistic reduction potentials were identified and quantified. The total GHG emissions for the U.S. aluminum cycle in 2006 amount to 38 Mt CO(2)-equivalence. However, the U.S. has increasingly relied on imports of aluminum embodied in various products. The in-use stock is still growing fast in most product categories, which limits current scrap availability for recycling and emissions saving. Nevertheless, there is still large emission mitigation potential through recycling. The potentials from "100% old scrap collection" and "low emission energy" were each calculated to be higher than all process technology potential. Total emissions will decrease dramatically and mitigation priorities will change significantly under a stock saturation situation as much more old scrap becomes available for recycling. The nature of in-use stock development over the coming decades will be decisive for the aluminum industry to reach deeper emission cuts. PMID- 21970674 TI - pH manipulation: a facile method for lowering oxidation state and keeping good yield of poly(m-phenylenediamine) and its powerful Ag+ adsorption ability. AB - A method of pH manipulation has been used to improve chemically oxidative polymerization of m-phenylenediamine (mPD) through concurrent addition of NaOH when adding oxidant (NH(4))(2)S(2)O(8). pH detection and open-circuit potential technique were adopted to monitor the polymerization process of mPD and to explain the oxidation state-pH and yield-pH relationships. Results from Fourier transformed infrared (FTIR) and X-ray photoelectron (XPS) spectroscopies indicate that a low oxidation state is under control by regulating NaOH concentration. At 2.5 M NaOH, the oxidation state of poly(m-phenylenediamine) (PmPD) is 64.7 mol % (measured by molar content of quinoid imine from XPS), while the yield is 84%. The synthesized PmPD possesses better Ag(+) adsorption performance when lowering its oxidation state. Moreover, the Ag(+) adsorbance of PmPD can reach 1693 mg g( 1). Meanwhile, Ag(+) adsorption mechanism was studied by pH tracking, X-ray diffraction (XRD) patterns, and X-ray photoelectron spectroscopy. The adsorption process includes redox reaction, chelation, and physical adsorption. PMID- 21970675 TI - High sensitivity of an ELISA kit for detection of the gamma-isoform of 14-3-3 proteins: usefulness in laboratory diagnosis of human prion disease. AB - BACKGROUND: The gamma-isoform of the 14-3-3 protein (14-3-3 gamma) is expressed in neurons, and could be a specific marker for neuronal damage. This protein has been reported as a detectable biomarker, especially in the cerebrospinal fluid (CSF) of Creutzfeldt-Jakob disease (CJD) patients by Western blotting (WB) or enzyme-linked immunosorbent assays (ELISAs). Western blotting for 14-3-3 gamma is not sensitive, and the reported data are conflicting among publications. An ELISA specific for 14-3-3 gamma is not available. METHODS: CJD patients (n=114 sporadic CJD patients, 7 genetic CJD, and 3 iatrogenic CJD) and 99 patients with other neurodegenerative diseases were examined in this study. The CSF samples obtained were analyzed by Western blotting for 14-3-3 gamma, and by ELISA for total tau protein. We evaluated the sensitivity and specificity of the newly developed sandwich ELISA for 14-3-3 gamma. RESULTS: The cut-off value of the 14-3-3 gamma ELISA was >1, 683 AU/ml; and sensitivity was 95.2%, with 72.7% specificity. This specificity was the same for the total tau protein ELISA. Seven CJD cases were negative by WB but positive using the 14-3-3 gamma ELISA, indicating that the ELISA is more sensitive. All 21 cases of early stage CJD could be diagnosed using a combination of the 14-3-3gamma ELISA and diffusion weighted MR imaging (DWI MRI). CONCLUSION: The 14-3-3 gamma ELISA was more sensitive than conventional WB, and was useful for laboratory diagnosis of CJD, similar to the ELISA for the tau protein. Using DWI-MRI and these ELISA tests on CSF, diagnosis of CJD will be possible even at early stages of the disease. PMID- 21970676 TI - Kinase inhibitors can produce off-target effects and activate linked pathways by retroactivity. AB - BACKGROUND: It has been shown in experimental and theoretical work that covalently modified signaling cascades naturally exhibit bidirectional signal propagation via a phenomenon known as retroactivity. An important consequence of retroactivity, which arises due to enzyme sequestration in covalently modified signaling cascades, is that a downstream perturbation can produce a response in a component upstream of the perturbation without the need for explicit feedback connections. Retroactivity may, therefore, play an important role in the cellular response to a targeted therapy. Kinase inhibitors are a class of targeted therapies designed to interfere with a specific kinase molecule in a dysregulated signaling pathway. While extremely promising as anti-cancer agents, kinase inhibitors may produce undesirable off-target effects by non-specific interactions or pathway cross-talk. We hypothesize that targeted therapies such as kinase inhibitors can produce off-target effects as a consequence of retroactivity alone. RESULTS: We used a computational model and a series of simple signaling motifs to test the hypothesis. Our results indicate that within physiologically and therapeutically relevant ranges for all parameters, a targeted inhibitor can naturally induce an off-target effect via retroactivity. The kinetics governing covalent modification cycles in a signaling network were more important for propagating an upstream off-target effect in our models than the kinetics governing the targeted therapy itself. Our results also reveal the surprising and crucial result that kinase inhibitors have the capacity to turn "on" an otherwise "off" parallel cascade when two cascades share an upstream activator. CONCLUSIONS: A proper and detailed characterization of a pathway's structure is important for identifying the optimal protein to target as well as what concentration of the targeted therapy is required to modulate the pathway in a safe and effective manner. We believe our results support the position that such characterizations should consider retroactivity as a robust potential source of off-target effects induced by kinase inhibitors and other targeted therapies. PMID- 21970684 TI - Molecular cloning, spatial and temporal expression analysis of CatSper genes in the Chinese Meishan pigs. AB - BACKGROUND: Sperm ion channel proteins (CatSpers) are essential for sperm hyperactivated motility, and then penetration through the zona pellucida. The CatSper class of proteins have well been characterized in the mouse and human. However, such data for pigs are not available. In the present study, we cloned the porcine CatSper 1-4 genes, analysed their spatial expression in various organs and temporal expression in the testes from birth until sexual maturity in Meishan boars. METHODS: Rapid amplification of cDNA ends (RACE) was performed to clone the full length cDNAs of porcine CatSper genes and bioinformatics analysis of inferred CatSper proteins was also determined. Various organs were collected from 150 day-old pigs to characterize the spatial expression of CatSper genes by qualitative reverse transcriptase polymerase chain reaction (RT-PCR), and testes from birth to 150 day-old boars were sampled to detect the temporal expression of CatSper genes by quantitative real-time RT-PCR. RESULTS: The mRNA sequences of CatSper1 (2452 bp), CatSper2 (2038 bp), CatSper3 (1408 bp), and CatSper4 (1799 bp), including full length of cDNAs, 5' and 3' flanks, were obtained. The bioinformatics analysis indicated that coding regions spanning the ion transport domains were conserved for different species analyzed. Among the four CatSpers, CatSper2, 3, and 4 were more conserved across species, compared with CatSper1. In addition, six conservative trans-membrane domains, a pore forming motif, and a coiled-coil motif were also identified. The spatial analysis from different organs showed that CatSper1 was detected in both testes and hypothalamus, CatSper2 was restricted in testes only, CatSper4 was expressed in testes and rete testes; whereas CatSper3 was more ubiquitously. CatSper3 and CatSper4 transcripts were also detected in ejaculated sperm. At Days 1 and 30 of age, CatSper mRNAs exhibited only sparse expression in the testes. However, these transcripts highly expressed at Day 60 and onward till sexual maturity (Day 150 of age). CONCLUSIONS: The spatial and temporal expression profiles of CatSper genes were reported herein for the first time in pigs. CatSper1, CatSper2 and CatSper4 were primarily expressed in testes, while CatSper3 transcript was prevalent in a variety of organs. CatSper3 and CatSper4 mRNAs were present in mature sperm cells. Substantial upregulation of CatSper genes was initiated at Day 60 and maintained this marked production until sexual maturity. PMID- 21970685 TI - Genome-wide distribution of genetic diversity and linkage disequilibrium in elite sugar beet germplasm. AB - BACKGROUND: Characterization of population structure and genetic diversity of germplasm is essential for the efficient organization and utilization of breeding material. The objectives of this study were to (i) explore the patterns of population structure in the pollen parent heterotic pool using different methods, (ii) investigate the genome-wide distribution of genetic diversity, and (iii) assess the extent and genome-wide distribution of linkage disequilibrium (LD) in elite sugar beet germplasm. RESULTS: A total of 264 and 238 inbred lines from the yield type and sugar type inbreds of the pollen parent heterotic gene pools, respectively, which had been genotyped with 328 SNP markers, were used in this study. Two distinct subgroups were detected based on different statistical methods within the elite sugar beet germplasm set, which was in accordance with its breeding history. MCLUST based on principal components, principal coordinates, or lapvectors had high correspondence with the germplasm type information as well as the assignment by STRUCTURE, which indicated that these methods might be alternatives to STRUCTURE for population structure analysis. Gene diversity and modified Roger's distance between the examined germplasm types varied considerably across the genome, which might be due to artificial selection. This observation indicates that population genetic approaches could be used to identify candidate genes for the traits under selection. Due to the fact that r2 >0.8 is required to detect marker-phenotype association explaining less than 1% of the phenotypic variance, our observation of a low proportion of SNP loci pairs showing such levels of LD suggests that the number of markers has to be dramatically increased for powerful genome-wide association mapping. CONCLUSIONS: We provided a genome-wide distribution map of genetic diversity and linkage disequilibrium for the elite sugar beet germplasm, which is useful for the application of genome-wide association mapping in sugar beet as well as the efficient organization of germplasm. PMID- 21970686 TI - Computational and in vitro studies on the inhibitory effects of herbal compounds on human cytochrome P450 1A2. AB - Human CYP1A2 is an important enzyme for drug metabolism and procarcinogen activation. This study aimed to explore the binding mode of ligands with CYP1A2 and to screen potential inhibitors from a library of herbal compounds using computational and in vitro approaches. The heme prosthetic group and six residues (Thr124, Phe125, Phe226, Phe260, Gly316, and Ala317) in the active site of CYP1A2 were identified as important residues for ligand binding using the LIGPLOT program. Ala317 in helix I immediately above heme was highly conserved in most human CYPs with known crystal structures. In molecular docking, 19 of the 56 herbal compounds examined were identified as potential inhibitors of CYP1A2. Up to 21 of the 56 herbal compounds were hit by the pharmacophore model of CYP1A2 inhibitors developed and validated in this study. In the in vitro inhibition study, 8 herbal compounds were identified as moderate to potent inhibitors of CYP1A2. Five of the 8 herbal compounds predicted to be potential inhibitors were confirmed as CYP1A2 inhibitors in the in vitro study. A combination of computational and in vitro approaches, represent a useful tool to identify potential inhibitors for CYP1A2 from herbal compounds. PMID- 21970687 TI - Full efficacy with no CNS side-effects: unachievable panacea or reality? DMPK considerations in design of drugs with limited brain penetration. AB - Optimising drug properties can be an important strategy to limit penetration into the CNS and offers advantages in reducing the risk of undesirable neurological effects When considering the design of these drugs it is important to consider the relative influx and efflux rates at the relevant biological membranes The highest degree of restriction at the brain is probably achievable by utilising active transport to exclude compounds from the brain Affinity for the efflux transporters Pgp and BCRP has been achieved in two in-house chemistry programmes by increasing polar surface area, which resulted in highly orally bioavailable low CNS penetrant compounds in preclinical species. PMID- 21970689 TI - Enantioselective Michael addition of malonates to 2-enoylpyridine N-oxides catalyzed by chiral bisoxazoline-Zn(II) complex. AB - An enantioselective Michael addition of malonates to 2-enoylpyridine N-oxides catalyzed by a chiral bisoxazoline-Zn(II) complex has been developed. The corresponding Michael adducts have been obtained in high yields with up to 96% ee. A plausible transition-state model has been proposed to explain the stereochemical outcome of the reaction. PMID- 21970688 TI - Effects of plasma concentrations of 5-fluorouracil on long-term survival after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma. AB - BACKGROUND: A substantial body of literature has accumulated during the past 20 years showing the plasma concentrations of 5-fluorouracil (5-FU) to correlate with clinical response and/or toxicity in colorectal cancer, and head and neck cancer, but little information is available concerning effects on long-term survival. Here, Japanese patients with esophageal squamous cell carcinoma (ESCC) were followed up for 5 years after treatment with a definitive 5-FU/cisplatin (CDDP)-based chemoradiotherapy (CRT), and the association between prognosis and the plasma concentration of 5-FU was evaluated. METHODS: Forty-nine patients with ESCC, who were treated with a definitive 5-FU/CDDP-based CRT, were enrolled. A course consisted of the continuous infusion of 5-FU at 400 mg/m2/day for days 1-5 and 8-12, the infusion of CDDP at 40 mg/m2/day on days 1 and 8, and the radiation at 2 Gy/day on days 1 to 5, 8 to 12, and 15 to 19, with a second course repeated after a 2-week interval. Plasma concentrations of 5-FU were determined by high performance liquid chromatography at 5:00 PM on days 3, 10, 38 and 45, and at 5:00 AM on days 4, 11, 39 and 46. RESULTS: The overall 5-year survival rate was 42.9%. Age (P = 0.020), body weight (P = 0.019), and disease stage (P = 0.048) affected the survival, and the survival depended on the clinical response assessed at 1 month after the treatment (P = 0.001). Higher plasma concentrations of 5-FU resulted in a better clinical response (P = 0.043), and trended to prolong survival (P = 0.321). CONCLUSIONS: The long-term survival after treatment with a definitive 5-FU/CDDP-based CRT possibly depends on the plasma concentrations of 5-FU, and further clinical studies with a larger number of cases are needed to clarify the relationship between them. PMID- 21970690 TI - Cultural modulation of self-referential brain activity for personality traits and social identities. AB - Cross-cultural studies have shown that personality traits are less central and social identities are more important to the selfhood of collectivistic people. However, most cultural neuroscience studies using the self-reference effect (SRE) paradigm have only used personality traits to explore cultural differences in the neural circuits of self-referential processes. In the present study, we used both personality traits and social identities as stimuli in the SRE paradigm and investigated whether and how one's cultural orientation (i.e., individualism vs. collectivism) affects the SRE in the brain. The results showed that the medial prefrontal cortex, anterior cingulate, bilateral temporoparietal regions, and precuneus were involved in self-representation for both personality traits and social identities. Importantly, cultural orientation predicted differential activation patterns in these regions. Collectivists showed stronger activation in the left temporoparietal regions than individualists, who mainly recruited the medial prefrontal regions. Our findings suggest that the personal and social self share common neural substrates, the activation of which can be modulated by one's cultural orientation. PMID- 21970691 TI - The Cucumber vein yellowing virus silencing suppressor P1b can functionally replace HCPro in Plum pox virus infection in a host-specific manner. AB - Plant viruses of the genera Potyvirus and Ipomovirus (Potyviridae family) use unrelated RNA silencing suppressors (RSS) to counteract antiviral RNA silencing responses. HCPro is the RSS of Potyvirus spp., and its activity is enhanced by the upstream P1 protein. Distinctively, the ipomovirus Cucumber vein yellowing virus (CVYV) lacks HCPro but contains two P1 copies in tandem (P1aP1b), the second of which functions as RSS. Using chimeras based on the potyvirus Plum pox virus (PPV), we found that P1b can functionally replace HCPro in potyviral infections of Nicotiana plants. Interestingly, P1a, the CVYV protein homologous to potyviral P1, disrupted the silencing suppression activity of P1b and reduced the infection efficiency of PPV in Nicotiana benthamiana. Testing the influence of RSS in host specificity, we found that a P1b-expressing chimera poorly infected PPV's natural host, Prunus persica. Conversely, P1b conferred on PPV chimeras the ability to replicate locally in cucumber, CVYV's natural host. The deleterious effect of P1a on PPV infection is host dependent, because the P1aP1b expressing PPV chimera accumulated in cucumber to higher levels than PPV expressing P1b alone. These results demonstrate that a potyvirus can use different RSS, and that particular RSS and upstream P1-like proteins contribute to defining the virus host range. PMID- 21970692 TI - Functional characteristics of an endophyte community colonizing rice roots as revealed by metagenomic analysis. AB - Roots are the primary site of interaction between plants and microorganisms. To meet food demands in changing climates, improved yields and stress resistance are increasingly important, stimulating efforts to identify factors that affect plant productivity. The role of bacterial endophytes that reside inside plants remains largely unexplored, because analysis of their specific functions is impeded by difficulties in cultivating most prokaryotes. Here, we present the first metagenomic approach to analyze an endophytic bacterial community resident inside roots of rice, one of the most important staple foods. Metagenome sequences were obtained from endophyte cells extracted from roots of field-grown plants. Putative functions were deduced from protein domains or similarity analyses of protein-encoding gene fragments, and allowed insights into the capacities of endophyte cells. This allowed us to predict traits and metabolic processes important for the endophytic lifestyle, suggesting that the endorhizosphere is an exclusive microhabitat requiring numerous adaptations. Prominent features included flagella, plant-polymer-degrading enzymes, protein secretion systems, iron acquisition and storage, quorum sensing, and detoxification of reactive oxygen species. Surprisingly, endophytes might be involved in the entire nitrogen cycle, as protein domains involved in N(2)-fixation, denitrification, and nitrification were detected and selected genes expressed. Our data suggest a high potential of the endophyte community for plant-growth promotion, improvement of plant stress resistance, biocontrol against pathogens, and bioremediation, regardless of their culturability. PMID- 21970693 TI - Microarray analysis shows that recessive resistance to Watermelon mosaic virus in melon is associated with the induction of defense response genes. AB - Resistance to Watermelon mosaic virus (WMV) in melon (Cucumis melo L.) accession TGR-1551 is characterized by a significant reduction in virus titer, and is inherited as a recessive, loss-of-susceptibility allele. We measured virus RNA accumulation in TGR-1551 plants and a susceptible control ('Tendral') by real time quantitative polymerase chain reaction, and also profiled the expression of 17,443 unigenes represented on a melon microarray over a 15-day time course. The virus accumulated to higher levels in cotyledons of the resistant variety up to 9 days postinoculation (dpi) but, thereafter, levels increased in the susceptible variety while those in the resistant variety declined. Microarray experiments looking at the early response to infection (1 and 3 dpi), as well as responses after 7 and 15 dpi, revealed more profound transcriptomic changes in resistant plants than susceptible ones. The gene expression profiles revealed deep and extensive transcriptome remodeling in TGR-1551 plants, often involving genes with pathogen response functions. Overall, our data suggested that resistance to WMV in TGR-1551 melon plants is associated with a defense response, which contrasts with the recessive nature of the resistance trait. PMID- 21970694 TI - Prevalence of high-risk alleles in the LOXL1 gene and its association with pseudoexfoliation syndrome and exfoliation glaucoma in a Latin American population. AB - PURPOSE: Pseudoexfoliation syndrome (XFS) is a major risk factor for exfoliation glaucoma (XFG). A significant association exists between XFG and several SNPs in the lysyl oxidase-like 1 (LOXL1) gene. The purpose of this study was to report the results of the first association study between LOXL1 polymorphisms and XFS and/or XFG in a Latin American population. METHODS: Genotypes of three high-risk SNPs of LOXL1 (rs1048661, rs3825942, and rs2165241) were analyzed by direct sequencing. A case-control study was conducted with 102 unrelated XFS/XFG Mexican patients (42 XFS/60 XFG) as well as 97 control subjects. Allele frequencies, Hardy-Weinberg equilibrium, and haplotype association analysis were assessed with the Haplo View software. RESULTS: The T allele of the intronic SNP rs2165241 was more frequent in XFS/XFG patients than in controls (OR [95% CI] = 2.41 [1.59 3.64]; p = 0.00001). The G allele of rs3825942 was found in a higher frequency in XFS/XFG than in controls (100% vs 95% respectively, p = 0.0019). No significant association between XFS and the rs1048661 (R141L) SNP was observed. The TGT haplotype was observed in a higher frequency in patients than in controls (p = 0.025), and produced the highest risk in our study (OR [95% CI] = 3.20 [1.09 9.39]; p = 0.025). CONCLUSIONS: This is the first study associating LOXL1 gene polymorphism and XFS/XFG in Latin America. LOXL1 variants are associated with an elevated risk for XFS/XFG in the Mexican population. A higher risk was conferred by the T allele of the intronic rs2165241 SNP rather than by the worldwide "high risk" G allele of rs3825942. PMID- 21970695 TI - The relation of nasality and nasalance to nasal port area based on a computational model. AB - OBJECTIVE: The purpose of this study was to examine the relation of perceptual ratings of nasality by experienced listeners, measures of nasalance, and the size of the nasal port opening for three simulated English corner vowels, /i/, /u/, and /a/. DESIGN: Samples were generated using a computational model that allowed for exact control of nasal port size and a direct measure of nasalance. Perceptual ratings were obtained using a paired-stimulus presentation. PARTICIPANTS: Five experienced listeners. MAIN OUTCOME MEASURES: Measures of nasalance and perceptual nasality ratings. RESULTS: Differences in nasalance and perceptual ratings of nasality were noted among the three vowels, with values being greater for the high vowels /i/ and /u/ compared to the low vowel /a/. Listeners detected nasality for the high and low vowels simulated with nasal port areas of 0.01 and 0.15 cm(2), respectively. Correlations between ratings of nasality and nasalance were high for all three vowels. CONCLUSIONS: Results of the present study show a high correlation between ratings of nasality and measures of nasalance for nasal port areas ranging from 0 to 0.5 cm(2). The correlations were based on sustained vowel samples. The restricted speech sample limits generalization of the findings to clinical data; however, the results are a demonstration of the usefulness of modeling to understand the perceptual phenomena of nasality. PMID- 21970696 TI - Manganese triazacyclononane oxidation catalysts grafted under reaction conditions on solid cocatalytic supports. AB - Manganese complexes of 1,4,7-trimethyl-1,4,7-triazacyclononane (tmtacn) are highly active and selective alkene oxidation catalysts with aqueous H(2)O(2). Here, carboxylic acid-functionalized SiO(2) simultaneously immobilizes and activates these complexes under oxidation reaction conditions. H(2)O(2) and the functionalized support are both necessary to transform the inactive [(tmtacn)Mn(IV)(MU-O)(3)Mn(IV)(tmtacn)](2+) into the active, dicarboxylate bridged [(tmtacn)Mn(III)(MU-O)(MU-RCOO)(2)Mn(III)(tmtacn)](2+). This transformation is assigned on the basis of comparison of diffuse reflectance UV visible spectra to known soluble models, assignment of oxidation state by Mn K edge X-ray absorption near-edge spectroscopy, the dependence of rates on the acid/Mn ratios, and comparison of the surface structures derived from density functional theory with extended X-ray absorption fine structure. Productivity in cis-cyclooctene oxidation to epoxide and cis-diol with 2-10 equiv of solid cocatalytic supports is superior to that obtained with analogous soluble valeric acid cocatalysts, which require 1000-fold excess to reach similar levels at comparable times. Cyclooctene oxidation rates are near first order in H(2)O(2) and near zero order in all other species, including H(2)O. These observations are consistent with a mechanism of substrate oxidation following rate-limiting H(2)O(2) activation on the hydrated, supported complex. This general mechanism and the observed alkene oxidation activation energy of 38 +/- 6 kJ/mol are comparable to H(2)O(2) activation by related soluble catalysts. Undesired decomposition of H(2)O(2) is not a limiting factor for these solid catalysts, and as such, productivity remains high up to 25 degrees C and initial H(2)O(2) concentration of 0.5 M, increasing reactor throughput. These results show that immobilized carboxylic acids can be utilized and understood like traditional carboxylic acids to activate non-heme oxidation catalysts while enabling higher throughput and providing the separation and handling benefits of a solid catalyst. PMID- 21970697 TI - Effect of intervertebral disc degeneration on disc cell viability: a numerical investigation. AB - Degeneration of the intervertebral disc may be initiated and supported by impairment of the nutrition processes of the disc cells. The effects of degenerative changes on cell nutrition are, however, only partially understood. In this work, a finite volume model was used to investigate the effect of endplate calcification, water loss, reduction of disc height and cyclic mechanical loading on the sustainability of the disc cell population. Oxygen, lactate and glucose diffusion, production and consumption were modelled with non linear coupled partial differential equations. Oxygen and glucose consumption and lactate production were expressed as a function of local oxygen concentration, pH and cell density. The cell viability criteria were based on local glucose concentration and pH. Considering a disc with normal water content, cell death was initiated in the centre of the nucleus for oxygen, glucose, and lactate diffusivities in the cartilaginous endplate below 20% of the physiological values. The initial cell population could not be sustained even in the non calcified endplates when a reduction of diffusion inside the disc due to water loss was modelled. Alterations in the disc shape such as height loss, which shortens the transport route between the nutrient sources and the cells, and cyclic mechanical loads, could enhance cell nutrition processes. PMID- 21970698 TI - Clinical characteristics, pharmacotherapy, and healthcare resource use among patients with fibromyalgia newly prescribed pregabalin or tricyclic antidepressants. AB - OBJECTIVE: To examine treatment patterns and costs among patients with fibromyalgia prescribed pregabalin or tricyclic antidepressants (TCAs). METHODS: Using the LifeLinkTM Health Plan Claims Database, patients with fibromyalgia (International Classification of Diseases, Ninth Revision, Clinical Modification code 729.1X) newly prescribed (index date) TCAs (n = 898) were identified and propensity score-matched (PSM) with patients newly prescribed pregabalin (n = 898). Pain-related pharmacotherapy, comorbidities, and healthcare resource use/costs were examined during the 12 months, pre-index, and follow-up periods. RESULTS: Both patient groups reported multiple comorbidities and received pain medications in the pre-index and follow-up periods. Among patients prescribed pregabalin, use of non-selective non-steroidal anti-inflammatory drugs (43.3% vs 39.8%), other anticonvulsants (28.6% vs 23.3%), and tetracyclic/miscellaneous antidepressants (28.5% vs 25.8%) significantly decreased, and cyclooxygenase 2 (COX-2) inhibitors (7.7% vs 10.4%), TCAs (4.8% vs 7.9%), and topical agents (10.8% vs 15.1%) increased in the follow-up period (p < 0.05). Among patients prescribed TCAs, there were significant decreases in muscle relaxants (42.0% vs 38.4%) and sedative hypnotics (27.4% vs 23.9%), and increases in COX-2 inhibitors (5.8% vs 7.9%) and anticonvulsants (25.1% vs 33.7%; p < 0.05). There were increases (p < 0.0001) in pharmacy costs in both cohorts and total healthcare costs in the pregabalin cohort from pre-index to follow-up. Median total costs were higher (p < 0.05) in the pregabalin group vs TCAs in the pre-index ($9935 vs $8771) and follow-up ($10,689 vs $8379) periods. LIMITATIONS: Despite attempts to address bias through PSM, the higher pre-index costs in the pregabalin cohort suggest a channeling of patients with more severe fibromyalgia to pregabalin. CONCLUSIONS: Patients with fibromyalgia prescribed pregabalin or TCAs had multiple comorbidities and a sizeable pain medication burden, which increased in the follow-up period for both cohorts. Only 5% of pregabalin initiators had been treated with concomitant TCAs at baseline, suggesting that TCAs were inappropriate for these patients owing to their contraindications. PMID- 21970699 TI - Clinical comorbidities, treatment patterns, and healthcare costs among patients with fibromyalgia newly prescribed pregabalin or duloxetine in usual care. AB - OBJECTIVE: To assess comorbidities, pain-related pharmacotherapy, and healthcare resource use among patients with fibromyalgia (FM) newly prescribed pregabalin or duloxetine (index event) in usual care settings. METHODS: Using the LifeLinkTM Health Plan Claims Database, patients with FM (International Classification of Diseases, Ninth Revision, Clinical Modification code 729.1X) were identified. Patients initiated on duloxetine were propensity score-matched with patients initiated on pregabalin (n = 826; mean age [standard deviation] of 48.3 [9.3] years for both groups). Prevalence of comorbidities, pain-related pharmacotherapy, and healthcare resource use/costs were examined during the 12 month pre-index and follow-up periods. RESULTS: Both patient groups had multiple comorbidities and a substantial pain-related and adjuvant medication burden. In the pregabalin group, use of other anticonvulsants decreased significantly (31.6% vs 24.9%), whereas use of serotonin-norepinephrine reuptake inhibitors (SNRIs; 16.5% vs 22.5%) and topical agents (10.1% vs 13.2%) increased in the follow-up period (p < 0.01). In the duloxetine group, there were significant decreases in the use of other SNRIs (13.0% vs 5.7%), selective serotonin reuptake inhibitors (41.3% vs 21.7%), and tricyclic antidepressants (18.8% vs 13.2%), and an increase in the use of anticonvulsants (28.6% vs 40.1%; p < 0.0001). There were significant increases (p < 0.0001) in pharmacy and total healthcare costs in both cohorts, and a significant increase in outpatient costs (p = 0.0084) in the duloxetine cohort from pre-index to follow-up. There were no significant differences in median total healthcare costs between the pregabalin and duloxetine groups in both the pre-index ($10,159 vs $9,556) and follow-up ($11,390 vs $11,746) periods. LIMITATIONS: Limitations of this study are typical of those associated with retrospective database analyses. CONCLUSIONS: Patients with FM prescribed pregabalin or duloxetine were characterized by a significant comorbidity and pain/adjuvant medication burden. Although healthcare costs increased in both groups, there were no statistically significant differences in direct healthcare costs between the two groups. PMID- 21970700 TI - Chemical looping combustion in a rotating bed reactor--finding optimal process conditions for prototype reactor. AB - A lab-scale rotating bed reactor for chemical looping combustion has been designed, constructed, and tested using a CuO/Al(2)O(3) oxygen carrier and methane as fuel. Process parameters such as bed rotating frequency, gas flows, and reactor temperature have been varied to find optimal performance of the prototype reactor. Around 90% CH(4) conversion and >90% CO(2) capture efficiency based on converted methane have been obtained. Stable operation has been accomplished over several hours, and also--stable operation can be regained after intentionally running into unstable conditions. Relatively high gas velocities are used to avoid fully reduced oxygen carrier in part of the bed. Potential CO(2) purity obtained is in the range 30 to 65%--mostly due to air slippage from the air sector--which seems to be the major drawback of the prototype reactor design. Considering the prototype nature of the first version of the rotating reactor setup, it is believed that significant improvements can be made to further avoid gas mixing in future modified and up-scaled reactor versions. PMID- 21970702 TI - Measuring and analyzing tissue specificity of human genes and protein complexes. AB - Proteins and their interactions are essential for the survival of each human cell. Knowledge of their tissue occurrence is important for understanding biological processes. Therefore, we analyzed microarray and high-throughput RNA sequencing data to identify tissue-specific and universally expressed genes. Gene expression data were used to investigate the presence of proteins, protein interactions and protein complexes in different tissues. Our comparison shows that the detection of tissue-specific genes and proteins strongly depends on the applied measurement technique. We found that microarrays are less sensitive for low expressed genes than high-throughput sequencing. Functional analyses based on microarray data are thus biased towards high expressed genes. This also means that previous biological findings based on microarrays might have to be re examined using high-throughput sequencing results. PMID- 21970701 TI - Nitric oxide involvement in the acrosome reaction triggered by leptin in pig sperm. AB - BACKGROUND: Nitric oxide (NO) is a signaling molecule produced by intracellular nitric oxide synthase (NOS) enzymes. This free radical appears to affect sperm capacitation, a maturation step preceding acrosome reaction. Recent studies have reported leptin ability to promote capacitation and acrosome reaction in pig male gametes. METHODS: This study has investigated nitric oxide production in leptin treated pig spermatozoa by fluorescence-activated cell sorting, while the intracellular NOS isoforms were assessed by Western blot analysis. In addition, acrosome status of treated-spermatozoa was evaluated by FITC-PNA staining. RESULTS: Significant increases of nitric oxide levels and acrosome reaction extent were detected in leptin-treated spermatozoa, but both the effects were reversed in presence of L-NAME. Furthermore, the immunoblots of sperm extracts have evidenced three bands of ~160 Kd(bNOS), ~130 Kd (iNOS) and ~135 Kd (eNOS). CONCLUSIONS: The identification of the three intracellular NOS isoforms suggests that pig spermatozoa could produce NO, while the augmented nitric oxide levels in leptin-treated male gametes indicates the capacity of the hormone to induce nitric oxide production. Furthermore, the inhibitory effect of L-NAME and of Ab ObR on the promotion of acrosome reaction triggered by leptin suggests a possible involvement of NO in the hormone action. PMID- 21970703 TI - Parabolic flight induces changes in gene expression patterns in Arabidopsis thaliana. AB - Our primary objective was to evaluate gene expression changes in Arabidopsis thaliana in response to parabolic flight as part of a comprehensive approach to the molecular biology of spaceflight-related adaptations. In addition, we wished to establish parabolic flight as a tractable operations platform for molecular biology studies. In a succession of experiments on NASA's KC-135 and C-9 parabolic aircraft, Arabidopsis plants were presented with replicated exposure to parabolic flight. Transcriptome profiling revealed that parabolic flight caused changes in gene expression patterns that stood the statistical tests of replication on three different flight days. The earliest response, after 20 parabolas, was characterized by a prominence of genes associated with signal transduction. After 40 parabolas, this prominence was largely replaced by genes associated with biotic and abiotic stimuli and stress. Among these responses, three metabolic processes stand out in particular: the induction of auxin metabolism and signaling, the differential expression of genes associated with calcium-mediated signaling, and the repression of genes associated with disease resistance and cell wall biochemistry. Many, but not all, of these responses are known to be involved in gravity sensing in plants. Changes in auxin-related gene expression were also recorded by reporter genes tuned to auxin signal pathways. These data demonstrate that the parabolic flight environment is appropriate for molecular biology research involving the transition to microgravity, in that with replication, proper controls, and analyses, gene expression changes can be observed in the time frames of typical parabolic flight experiments. PMID- 21970704 TI - An endogenous growth pattern of roots is revealed in seedlings grown in microgravity. AB - In plants, sensitive and selective mechanisms have evolved to perceive and respond to light and gravity. We investigated the effects of microgravity on the growth and development of Arabidopsis thaliana (ecotype Landsberg) in a spaceflight experiment. These studies were performed with the Biological Research in Canisters (BRIC) hardware system in the middeck region of the space shuttle during mission STS-131 in April 2010. Seedlings were grown on nutrient agar in Petri dishes in BRIC hardware under dark conditions and then fixed in flight with paraformaldehyde, glutaraldehyde, or RNAlater. Although the long-term objective was to study the role of the actin cytoskeleton in gravity perception, in this article we focus on the analysis of morphology of seedlings that developed in microgravity. While previous spaceflight studies noted deleterious morphological effects due to the accumulation of ethylene gas, no such effects were observed in seedlings grown with the BRIC system. Seed germination was 89% in the spaceflight experiment and 91% in the ground control, and seedlings grew equally well in both conditions. However, roots of space-grown seedlings exhibited a significant difference (compared to the ground controls) in overall growth patterns in that they skewed to one direction. In addition, a greater number of adventitious roots formed from the axis of the hypocotyls in the flight-grown plants. Our hypothesis is that an endogenous response in plants causes the roots to skew and that this default growth response is largely masked by the normal 1 g conditions on Earth. PMID- 21970705 TI - Searching for biosignatures using electron paramagnetic resonance (EPR) analysis of manganese oxides. AB - Manganese oxide (Mn oxide) minerals from bacterial sources produce electron paramagnetic resonance (EPR) spectral signatures that are mostly distinct from those of synthetic simulants and abiogenic mineral Mn oxides. Biogenic Mn oxides exhibit only narrow EPR spectral linewidths (~500 G), whereas abiogenic Mn oxides produce spectral linewidths that are 2-6 times broader and range from 1200 to 3000 G. This distinction is consistent with X-ray structural observations that biogenic Mn oxides have abundant layer site vacancies and edge terminations and are mostly of single ionic species [i.e., Mn(IV)], all of which favor narrow EPR linewidths. In contrast, abiogenic Mn oxides have fewer lattice vacancies, larger particle sizes, and mixed ionic species [Mn(III) and Mn(IV)], which lead to the broader linewidths. These properties could be utilized in the search for extraterrestrial physicochemical biosignatures, for example, on Mars missions that include a miniature version of an EPR spectrometer. PMID- 21970714 TI - Plasma 24S-hydroxycholesterol levels in elderly subjects with late onset Alzheimer's disease or vascular dementia: a case-control study. AB - BACKGROUND: In central nervous system cholesterol cannot be degraded but is secreted into circulation predominantly in the form of its polar metabolite 24(S) hydroxycholesterol (24S-OH-Chol). Some studies suggested an association between 24S-OH-Chol metabolism and different neurological diseases including dementia. A possible decrease in 24S-OH-Chol plasma levels has been reported late onset Alzheimer's disease (LOAD) and vascular dementia (VD), but results of previous studies are partially contradictory. METHODS: By high-speed liquid chromatography/tandem mass spectrometry we evaluated the plasma levels of 24S-OH Chol in a sample of 160 older individuals: 60 patients with LOAD, 35 patients with VD, 25 subjects affected by cognitive impairment no-dementia (CIND), and 40 (144 for genetics study) cognitively normal Controls. We also investigated the possible association between PPARgamma Pro12Ala polymorphism and dementia or 24S OH-Chol levels. RESULTS: Compared with Controls, plasma 24S-OH-Chol levels were higher in LOAD and lower in VD; a slight not-significant increase in CIND was observed (ANOVA p: 0.001). A positive correlation between 24S-OH-Chol/TC ratio and plasma C reactive protein (CRP) levels was found in the whole sample, independent of possible confounders (multiple regression p: 0.04; r2: 0.10). This correlation was strong in LOAD (r: 0.39), still present in CIND (r: 0.20), but was absent in VD patients (r: 0.08). The PPARgamma Pro12Ala polymorphism was not associated with the diagnosis of LOAD, VD, or CIND; no correlation emerged between the Ala allele and 24S-OH-Chol plasma levels. CONCLUSIONS: Our results suggest that plasma 24S-OH-Chol levels might be increased in the first stages of LOAD, and this phenomenon might be related with systemic inflammation. The finding of lower 24S-OH-Chol concentrations in VD might be related with a more advanced stage of VD compared with LOAD in our sample, and/or to different pathogenetic mechanisms and evolution of these two forms of dementia. PMID- 21970715 TI - Flare hypercalcemia after letrozole in a patient with liver metastasis from breast cancer: a case report. AB - INTRODUCTION: Tamoxifen may occasionally precipitate serious and potentially life threatening hypercalcemia. However, to date, this has not been documented with aromatase inhibitors. CASE PRESENTATION: A 65-year-old Japanese woman with liver metastasis from breast cancer was admitted to our hospital with vomiting, anorexia, fatigue, arthralgia, muscle pain and dehydration. She had started a course of letrozole five weeks earlier. Our patient's calcium level was 11.6 mg/dL. She was rehydrated and elcatonin was administered. Our patient's parathyroid hormone and parathyroid hormone-related protein levels were not increased and a bone scintigram revealed no evidence of skeletal metastasis. After our patient's serum calcium level returned to within the normal range, letrozole was restarted at one-half of the previous dose (1.25 mg). There were no episodes of hypercalcemia. However, 84 days after restarting letrozole, our patient again complained of arthralgia and treatment was changed to toremifene. During these periods, repeated ultrasonograms revealed no progression of liver metastasis. CONCLUSION: To the best of our knowledge, this is the first case report of flare hypercalcemia after treatment with letrozole in a patient with metastatic breast cancer. PMID- 21970706 TI - Incongruence between morphotypes and genetically delimited species in the coral genus Stylophora: phenotypic plasticity, morphological convergence, morphological stasis or interspecific hybridization? AB - BACKGROUND: Morphological data suggest that, unlike most other groups of marine organisms, scleractinian corals of the genus Stylophora are more diverse in the western Indian Ocean and in the Red Sea than in the central Indo-Pacific. However, the morphology of corals is often a poor predictor of their actual biodiversity: hence, we conducted a genetic survey of Stylophora corals collected in Madagascar, Okinawa, the Philippines and New Caledonia in an attempt to find out the true number of species in these various locations. RESULTS: A molecular phylogenetic analysis of the mitochondrial ORF and putative control region concurs with a haploweb analysis of nuclear ITS2 sequences in delimiting three species among our dataset: species A and B are found in Madagascar whereas species C occurs in Okinawa, the Philippines and New Caledonia. Comparison of ITS1 sequences from these three species with data available online suggests that species C is also found on the Great Barrier Reef, in Malaysia, in the South China Sea and in Taiwan, and that a distinct species D occurs in the Red Sea. Shallow-water morphs of species A correspond to the morphological description of Stylophora madagascarensis, species B presents the morphology of Stylophora mordax, whereas species C comprises various morphotypes including Stylophora pistillata and Stylophora mordax. CONCLUSIONS: Genetic analysis of the coral genus Stylophora reveals species boundaries that are not congruent with morphological traits. Of the four hypotheses that may explain such discrepancy (phenotypic plasticity, morphological stasis, morphological convergence, and interspecific hybridization), the first two appear likely to play a role but the fourth one is rejected since mitochondrial and nuclear markers yield congruent species delimitations. The position of the root in our molecular phylogenies suggests that the center of origin of Stylophora is located in the western Indian Ocean, which probably explains why this genus presents a higher biodiversity in the westernmost part of its area of distribution than in the "Coral Triangle". PMID- 21970717 TI - Au nanoparticle monolayers covered with sol-gel oxide thin films: optical and morphological study. AB - In this work, we provide a detailed study of the influence of thermal annealing on submonolayer Au nanoparticle deposited on functionalized surfaces as standalone films and those that are coated with sol-gel NiO and TiO(2) thin films. The systems are characterized through the use of UV-vis absorption, X-ray diffraction (XRD), atomic force microscopy (AFM), scanning electron microscopy (SEM), and spectroscopic ellipsometry. The surface plasmon resonance peak of the Au nanoparticles was found to red-shift and increase in intensity with increasing surface coverage, an observation that is directly correlated to the complex refractive index properties of Au nanoparticle layers. The standalone Au nanoparticles sinter at 200 degrees C, and a relationship between the optical properties and the annealing temperature is presented. When overcoated with sol gel metal oxide films (NiO, TiO(2)), the optical properties of the Au nanoparticles are strongly affected by the metal oxide, resulting in an intense red shift and broadening of the plasmon band; moreover, the temperature-driven sintering is strongly limited by the metal oxide layer. Optical sensing tests for ethanol vapor are presented as one possible application, showing reversible sensing dynamics and confirming the effect of Au nanoparticles in increasing the sensitivity and in providing a wavelength dependent response, thus confirming the potential use of such materials as optical probes. PMID- 21970716 TI - Natural prenylated resveratrol analogs arachidin-1 and -3 demonstrate improved glucuronidation profiles and have affinity for cannabinoid receptors. AB - RATIONALE: The therapeutic promise of trans-resveratrol (tRes) is limited by poor bioavailability following rapid metabolism. We hypothesise that trans-arachidin-1 (tA1) and trans-arachidin-3 (tA3), peanut hairy root-derived isoprenylated analogs of tRes, will exhibit slower metabolism/enhanced bioavailability and retain biological activity via cannabinoid receptor (CBR) binding relative to their non-prenylated parent compounds trans-piceatannol (tPice) and tRes, respectively. RESULTS: The activities of eight human UDP-glucuronosyltransferases (UGTs) toward these compounds were evaluated. The greatest activity was observed for extrahepatic UGTs 1A10 and 1A7, followed by hepatic UGTs 1A1 and 1A9. Importantly, an additional isoprenyl and/or hydroxyl group in tA1 and tA3 slowed overall glucuronidation. CBR binding studies demonstrated that all analogs bound to CB1Rs with similar affinities (5-18 uM); however, only tA1 and tA3 bound appreciably to CB2Rs. Molecular modelling studies confirmed that the isoprenyl moiety of tA1 and tA3 improved binding affinity to CB2Rs. Finally, although tA3 acted as a competitive CB1R antagonist, tA1 antagonised CB1R agonists by both competitive and non-competitive mechanisms. CONCLUSIONS: Prenylated stilbenoids may be preferable alternatives to tRes due to increased bioavailability via slowed metabolism. Similar structural analogs might be developed as novel CB therapeutics for obesity and/or drug dependency. PMID- 21970718 TI - An integrated approach identifies IFN-regulated microRNAs and targeted mRNAs modulated by different HCV replicon clones. AB - BACKGROUND: Infections with hepatitis C virus (HCV) progress to chronic phase in 80% of patients. To date, the effect produced by HCV on the expression of microRNAs (miRs) involved in the interferon-beta (IFN-beta) antiviral pathway has not been explored in details. Thus, we compared the expression profile of 24 selected miRs in IFN-beta-treated Huh-7 cells and in three different clones of Huh-7 cells carrying a self-replicating HCV RNA which express all viral proteins (HCV replicon system). METHODS: The expression profile of 24 selected miRs in IFN beta-treated Huh-7 cells and in HCV replicon 21-5 clone with respect to Huh-7 parental cells was analysed by real-time PCR. To exclude clone specific variations, the level of 16 out of 24 miRs, found to be modulated in 21-5 clone, was evaluated in two other HCV replicon clones, 22-6 and 21-7. Prediction of target genes of 3 miRs, confirmed in all HCV clones, was performed by means of miRGator program. The gene dataset obtained from microarray analysis of HCV clones was farther used to validate target prediction. RESULTS: The expression profile revealed that 16 out of 24 miRs were modulated in HCV replicon clone 21 5. Analysis in HCV replicon clones 22-6 and 21-7 indicated that 3 out of 16 miRs, (miR-128a, miR-196a and miR-142-3p) were modulated in a concerted fashion in all three HCV clones. Microarray analysis revealed that 37 out of 1981 genes, predicted targets of the 3 miRs, showed an inverse expression relationship with the corresponding miR in HCV clones, as expected for true targets. Classification of the 37 genes by Panther System indicated that the dataset contains genes involved in biological processes that sustain HCV replication and/or in pathways potentially implicated in the control of antiviral response by HCV infection. CONCLUSIONS: The present findings reveal that 3 IFN-beta-regulated miRs and 37 genes, which are likely their functional targets, were commonly modulated by HCV in three replicon clones. The future use of miR inhibitors or mimics and/or siRNAs might be useful for the development of diagnostic and therapeutic strategies aimed at the recovering of protective innate responses in HCV infections. PMID- 21970720 TI - The emerging impact of social neuroscience on neuropsychiatry and clinical neuroscience. PMID- 21970719 TI - Global discourses and experiential speculation: Secondary and tertiary graduate Malawians dissect the HIV/AIDS epidemic. AB - BACKGROUND: Since the beginning of the HIV/AIDS epidemic, the perspectives of secondary and tertiary school graduates in sub-Saharan Africa regarding the effectiveness of government and international HIV/AIDS policies and programmes have not been thoroughly examined. When extensive monetary aid is directed toward "development" in a country like Malawi, it is the educated elites - secondary and tertiary graduates who are heavily involved and influential in the domestic re distribution and implementation of millions of dollars worth of aid - on whom international expectations fall to decrease the transmission of HIV. Many Malawian jobs related to public health and HIV/AIDS are created as a direct result of this funding and are occupied by the few secondary and tertiary graduates. Thus, it is a practical venture to understand their perspectives on highly contentious and heavily funded HIV/AIDS issues that affect their nation. METHODS: Qualitative data was collected in this study in efforts to discover in depth perspectives on the HIV/AIDS epidemic. Thirty-eight secondary and tertiary graduate Malawians took part in semi-structured interviews. Data was analysed using an early grounded theory approach and subsequent themes of "global discourses" and "experiential knowledge of HIV/AIDS" emerged. RESULTS: This group of Malawians frequently responded to questions regarding healthcare and access to medicine, sexual behaviours and methods of reducing the spread of HIV/AIDS by citing and explaining the widespread, international and "proper" responses. The secondary and tertiary graduate Malawians also discussed these same topics in terms of what they perceive or have experienced. Experiential responses, such as the counter-productivity of circumcision and condoms, the overestimation of HIV/AIDS prevalence, and calls for more authoritarian policing of commercial sex work, were remarkably divergent from the HIV/AIDS discourse. CONCLUSIONS: The opinions of this group of secondary and tertiary graduate Malawians do not always coincide with the current literature and policies. They give deeper insight into what is perceived and what may be taking place, and hint at what the future holds for their people. The widespread and divergent perspectives must be seriously considered because these experiences describe the potential positive and negative consequences that occur on the ground throughout Malawi as a result of HIV/AIDS policies. PMID- 21970721 TI - Linear and nonlinear optical properties of the thiophene/phenylene-based oligomer and polymer. AB - In this article, we investigate the linear and nonlinear optical properties of the thiophene/phenylene-based oligomer (SL128G) and polymer (FSE59) chemically modified with alquilic chains, which allow greater solubility and provide new optical properties. These compounds present a strong absorption in the UV-visible region, providing a wide transparence window in visible-IR, ideal for applications in nonlinear optics. Employing the Z-scan technique with femtosecond pulses, we show that these compounds exhibit considerable two-photon absorption (2PA), with two 2PA allowed states located at 650 and 800 nm for SL128G and 780 and 920 nm for FSE59. Moreover, we observe the resonance enhancement effect as the excitation wavelength approaches the lowest one-photon-allowed state. By modeling the 2PA spectra considering a four-energy-level diagram within of the sum-over-essential states approach, we obtained the spectroscopic parameters of the electronic transitions to low-energy singlet excited states. Additionally, photoluminescence excited by femtosecond and picosecond pulses were performed to confirm the order of the multiphoton process and estimate the fluorescence lifetime, respectively. PMID- 21970722 TI - The total synthesis of the crinine alkaloid hamayne via a Pd[0]-catalyzed intramolecular alder-ene reaction. AB - The racemic form of the title alkaloid, 1, has been prepared in 13 steps from the ring-fused gem-dibromocyclopropane 7. Key transformations include the thermally induced electrocyclic ring-opening of compound 7, the Pd[0]-catalyzed intramolecular Alder-ene (IMAE) reaction of the derived sulfonamide (+/-)-12, and the conversion of the ensuing C-3a-arylhexahydroindole (+/-)-16 into (+/-) hamayne via a Pictet-Spengler reaction. PMID- 21970723 TI - Emotional processing and executive functioning in children and adults with Tourette's syndrome. AB - Tourette's syndrome (TS) is predominantly a childhood disorder, with many of those who meet diagnostic criteria in childhood experiencing a remission of symptoms in adulthood. This indicates that the influence of TS on cognitive and emotional processing can best be understood by examining performance in both adults and children with TS. The present study examined emotional processing using a battery of face and prosody tasks with increasing levels of difficulty (same-different emotion discrimination, emotion naming, and emotion naming with conflict for prosody only). Experiment 1 compared the performance of children with TS-alone (n = 16) or TS+ADHD (n = 15) to healthy matched control children (n = 27). Compared to healthy control children, no significant group differences were found for those with TS-alone. Children with TS+ADHD showed subtle impairments on the more difficult emotion processing tasks relative to healthy control children, and differences were more pronounced for anger items (voice emotion naming, p < .05; voice emotion naming with conflict, p < .01). Experiment 2 compared the performance of adults with TS-alone (n = 23) to healthy matched controls (n = 21). No significant group differences were found, other than evidence of subtle impairment in the adults with TS-alone on the most complex task, again particularly for anger items (p < .05). Separate measurement of executive skills detected no evidence of impairment in children or adults with TS and little in the way of correlational evidence linking emotion recognition and executive skills. Implications of the findings for our understanding of emotion processing in TS are discussed. PMID- 21970724 TI - A fluorescence displacement assay for antidepressant drug discovery based on ligand-conjugated quantum dots. AB - The serotonin (5-hydroxytryptamine, 5-HT) transporter (SERT) protein plays a central role in terminating 5-HT neurotransmission and is the most important therapeutic target for the treatment of major depression and anxiety disorders. We report an innovative, versatile, and target-selective quantum dot (QD) labeling approach for SERT in single Xenopus oocytes that can be adopted as a drug-screening platform. Our labeling approach employs a custom-made, QD-tagged indoleamine derivative ligand, IDT318, that is structurally similar to 5-HT and accesses the primary binding site with enhanced human SERT selectivity. Incubating QD-labeled oocytes with paroxetine (Paxil), a high-affinity SERT specific inhibitor, showed a concentration- and time-dependent decrease in QD fluorescence, demonstrating the utility of our approach for the identification of SERT modulators. Furthermore, with the development of ligands aimed at other pharmacologically relevant targets, our approach may potentially form the basis for a multitarget drug discovery platform. PMID- 21970725 TI - An evaluation of the resonance frequency analysis device: examiner reliability and repeatability of readings. AB - Initial stability at the placement and development of osseointegration are 2 major issues for implant survival. Many of the presently used noninvasive methods of evaluating the stability of implants are highly subjective. The resonance frequency analysis (RFA) device is claimed to offer a more objective means to assess implant stability. Limited information is available on the interexaminer reliability and repeatability of the RFA device, used to measure implant stability. Two blind in vivo studies were conducted using 50 implant cases. In the first clinical study, 3 investigators took implant stability quotient (ISQ) readings for each implant to check the interoperator reliability for the RFA device. In the second clinical study, implant stability was measured by the same operator using the RFA device for each implant 3 times on the same day with a 15 minute interval, to check the repeatability of the RFA device. Within the limitations of this study, the RFA device demonstrated a high degree of interoperator reliability and repeatability. PMID- 21970726 TI - Determination of material parameters of the two-dimensional Holzapfel-Weizsacker type model based on uniaxial extension data of arterial walls. AB - Soft tissues are anisotropic materials yet a majority of mechanical property tests have been uniaxial, which often failed to recapitulate the tensile response in other directions. This paper aims to study the feasibility of determining material parameters of anisotropic tissues by uniaxial extension with a minimal loss of anisotropic information. We assumed that by preselecting a certain constitutive model, we could give the constitutive parameters based on uniaxial extension data from orthogonal strip samples. In our study, the Holzapfel Weizsacker type strain energy density function (H-W model) was used to determine the material parameters of arterial walls from two fresh donation bodies. The key points we applied were the relationships between strain components in uniaxial tensile tests and the methods of stochastic optimisation. Further numerical experiments were taken. The estimate-effect ratio, defined by the number of data with the precision of estimation less than 0.5% over whole size of data, was calculated to demonstrate the feasibility of our method. The material parameters for Chinese aorta and pulmonary artery were given with the maximum root mean square (RMS) errors 0.042, and the minimal estimate-effect ratio in numerical experiments was 90.79%. Our results suggest that the constitutive parameters of arterial walls can be determined from uniaxial extension data, given the passive mechanical behaviour governed by H-W model. This method may apply to other tissues using different constitutive models. PMID- 21970727 TI - Bathrocephaly: a head shape associated with a persistent mendosal suture. AB - Bathrocephaly, a deformity of the posterior skull with bulging of the midportion of the occipital bone, is often associated with a benign variant of the mendosal suture ( Mulliken and Le, 2008 ). The endochondral and membranous portions of the occipital bone converge at the mendosal suture, which normally closes during fetal life or early infancy. When it persists, it is associated with a characteristic head shape that requires no intervention. We review the clinical findings associated with postnatal persistence of the mendosal suture and discuss other factors that may be associated with bathrocephaly. PMID- 21970728 TI - Toward understanding reactive adsorption of ammonia on Cu-MOF/graphite oxide nanocomposites. AB - The adsorption of ammonia on HKUST-1 (a metal-organic framework, MOF) and HKUST 1/graphite oxide (GO) composites was investigated in two different experimental conditions. From the isotherms, the isosteric heats of adsorption were calculated from the Clausius-Clapeyron equation following the virial approach. The results on HKUST-1 were compared with those obtained using molecular simulation studies. All materials exhibit higher ammonia adsorption capacities than those reported in the literature. The ammonia adsorption on the composites is higher than that measured separately on the MOF component and on GO. The strong adsorption of ammonia caused by chemical interactions on different adsorption sites is evidenced by the trends in the isosteric heats of adsorption. The molecular simulations conducted on HKUST-1 support the trends observed experimentally. In particular, the strong chemisorption of ammonia on the metallic centers of HKUST 1 is confirmed. Nevertheless, higher adsorption capacities are predicted compared with the experimental results. This discrepancy is mainly assigned to the partial collapse of the MOF structure upon exposure to ammonia, which is not accounted for in the simulation study. PMID- 21970729 TI - Dose-response effects of estrogenic mycotoxins (zearalenone, alpha- and beta zearalenol) on motility, hyperactivation and the acrosome reaction of stallion sperm. AB - BACKGROUND: The aim of this study was to investigate the in vitro effects of the Fusarium fungus-derived mycotoxin, zearalenone and its derivatives alpha zearalenol and beta-zearalenol on motility parameters and the acrosome reaction of stallion sperm. Since the toxic effects of zearalenone and its derivatives are thought to result from their structural similarity to 17beta-estradiol, 17beta estradiol was used as a positive control for 'estrogen-like' effects. METHODS: Stallion spermatozoa were exposed in vitro to zearalenone, alpha-zearalenol, beta zearalenol or 17beta-estradiol at concentrations ranging from 1 pM - 0.1 mM. After 2 hours exposure, motility parameters were evaluated by computer-assisted analysis, and acrosome integrity was examined by flow cytometry after staining with fluoroscein-conjugated peanut agglutinin. RESULTS: Mycotoxins affected sperm parameters only at the highest concentration tested (0.1 mM) after 2 hours exposure. In this respect, all of the compounds reduced the average path velocity, but only alpha-zearalenol reduced percentages of motile and progressively motile sperm. Induction of motility patterns consistent with hyperactivation was stimulated according to the following rank of potency: alpha zearalenol > 17beta-estradiol > zearalenone = beta-zearalenol. The hyperactivity associated changes observed included reductions in straight-line velocity and linearity of movement, and an increase in the amplitude of lateral head displacement, while curvilinear velocity was unchanged. In addition, whereas alpha- and beta- zearalenol increased the percentages of live acrosome-reacted sperm, zearalenone and 17beta-estradiol had no apparent effect on acrosome status. In short, alpha-zearalenol inhibited normal sperm motility, but stimulated hyperactive motility in the remaining motile cells and simultaneously induced the acrosome reaction. Beta-zearalenol induced the acrosome reaction without altering motility. Conversely, zearalenone and 17beta-estradiol did not induce the acrosome reaction but induced hyperactive motility albeit to a different extent. CONCLUSIONS: Apparently, the mycotoxin zearalenone has 17beta estradiol-like estrogenic activity that enables it to induce hyperactivated motility of equine sperm cells, whereas the zearalenol derivatives induce premature completion of the acrosome reaction and thereby adversely affect stallion sperm physiology. The alpha form of zearalenol still possessed the estrogenic ability to induce hyperactivated motility, whereas its beta stereo isomere had lost this property. PMID- 21970730 TI - UHPLC-PDA-ESI/HRMS/MS(n) analysis of anthocyanins, flavonol glycosides, and hydroxycinnamic acid derivatives in red mustard greens (Brassica juncea Coss variety). AB - An UHPLC-PDA-ESI/HRMS/MS(n) profiling method was used for a comprehensive study of the phenolic components of red mustard greens ( Brassica juncea Coss variety) and identified 67 anthocyanins, 102 flavonol glycosides, and 40 hydroxycinnamic acid derivatives. The glycosylation patterns of the flavonoids were assigned on the basis of direct comparison of the parent flavonoid glycosides with reference compounds. The putative identifications were obtained from tandem mass data analysis and confirmed by the retention time, elution order, and UV-vis and high resolution mass spectra. Further identifications were made by comparing the UHPLC PDA-ESI/HRMS/MS(n) data with those of reference compounds in the polyphenol database and in the literature. Twenty-seven acylated cyanidin 3-sophoroside-5 diglucosides, 24 acylated cyanidin 3-sophoroside-5-glucosides, 3 acylated cyanidin triglucoside-5-glucosides, 37 flavonol glycosides, and 10 hydroxycinnamic acid derivatives were detected for the first time in brassica vegetables. At least 50 of them are reported for the first time in any plant materials. PMID- 21970731 TI - Sicily statement on classification and development of evidence-based practice learning assessment tools. AB - BACKGROUND: Teaching the steps of evidence-based practice (EBP) has become standard curriculum for health professions at both student and professional levels. Determining the best methods for evaluating EBP learning is hampered by a dearth of valid and practical assessment tools and by the absence of guidelines for classifying the purpose of those that exist. Conceived and developed by delegates of the Fifth International Conference of Evidence-Based Health Care Teachers and Developers, the aim of this statement is to provide guidance for purposeful classification and development of tools to assess EBP learning. DISCUSSION: This paper identifies key principles for designing EBP learning assessment tools, recommends a common taxonomy for new and existing tools, and presents the Classification Rubric for EBP Assessment Tools in Education (CREATE) framework for classifying such tools. Recommendations are provided for developers of EBP learning assessments and priorities are suggested for the types of assessments that are needed. Examples place existing EBP assessments into the CREATE framework to demonstrate how a common taxonomy might facilitate purposeful development and use of EBP learning assessment tools. SUMMARY: The widespread adoption of EBP into professional education requires valid and reliable measures of learning. Limited tools exist with established psychometrics. This international consensus statement strives to provide direction for developers of new EBP learning assessment tools and a framework for classifying the purposes of such tools. PMID- 21970732 TI - Cr(VI)/Cr(III) and As(V)/As(III) ratio assessments in Jordanian spent oil shale produced by aerobic combustion and Anaerobic Pyrolysis. AB - With the increase in the awareness of the public in the environmental impact of oil shale utilization, it is of interest to reveal the mobility of potentially toxic trace elements in spent oil shale. Therefore, the Cr and As oxidation state in a representative Jordanian oil shale sample from the El-Lajjoun area were investigated upon different lab-scale furnace treatments. The anaerobic pyrolysis was performed in a retort flushed by nitrogen gas at temperatures in between 600 and 800 degrees C (pyrolytic oil shale, POS). The aerobic combustion was simply performed in porcelain cups heated in a muffle furnace for 4 h at temperatures in between 700 and 1000 degrees C (burned oil shale, BOS). The high loss-on ignition in the BOS samples of up to 370 g kg(-1) results from both calcium carbonate and organic carbon degradation. The LOI leads to enrichment in the Cr concentrations from 480 mg kg(-1) in the original oil shale up to 675 mg kg(-1) in the >= 850 degrees C BOS samples. Arsenic concentrations were not much elevated beyond that in the average shale standard (13 mg kg(-1)). Synchrotron based X-ray absorption near-edge structure (XANES) analysis revealed that within the original oil shale the oxidation states of Cr and As were lower than after its aerobic combustion. Cr(VI) increased from 0% in the untreated or pyrolyzed oil shale up to 60% in the BOS ash combusted at 850 degrees C, while As(V) increased from 64% in the original oil shale up to 100% in the BOS ash at 700 degrees C. No Cr was released from original oil shale and POS products by the European compliance leaching test CEN/TC 292 EN 12457-1 (1:2 solid/water ratio, 24 h shaking), whereas leachates from BOS samples showed Cr release in the order of one mmol L(-1). The leachable Cr content is dominated by chromate as revealed by catalytic adsorptive stripping voltammetry (CAdSV) which could cause harmful contamination of surface and groundwater in the semiarid environment of Jordan. PMID- 21970733 TI - Antenatal risk factors for peanut allergy in children. AB - BACKGROUND: Prenatal factors may contribute to the development of peanut allergy. We evaluated the risk of childhood peanut allergy in association with pregnancy exposure to Rh immune globulin, folic acid and ingestion of peanut-containing foods. METHODS: We conducted a web-based case-control survey using the Anaphylaxis Canada Registry, a pre-existing database of persons with a history of anaphylaxis. A total of 1300 case children with reported peanut allergy were compared to 113 control children with shellfish allergy. All were evaluated for maternal exposure in pregnancy to Rh immune globulin and folic acid tablet supplements, as well as maternal avoidance of dietary peanut intake in pregnancy. RESULTS: Receipt of Rh immune globulin in pregnancy was not associated with a higher risk of peanut allergy (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.51 to 1.45), nor was initiation of folic acid tablet supplements before or after conception (OR 0.53, 95% CI 0.19 to 1.48). Complete avoidance of peanut containing products in pregnancy was associated with a non-significantly lower risk of peanut allergy (OR 0.53, 95% CI 0.27 to 1.03). CONCLUSION: The risk of childhood peanut allergy was not modified by the following common maternal exposures in pregnancy: Rh immune globulin, folic acid or peanut-containing foods. CLINICAL IMPLICATIONS: Rh immune globulin, folic acid supplement use and peanut avoidance in pregnancy have yet to be proven to modulate the risk of childhood anaphylaxis to peanuts. CAPSULE SUMMARY: Identification of prenatal factors that contribute to peanut allergy might allow for prevention of this life threatening condition. This article explores the role of three such factors. PMID- 21970734 TI - CTCF, cohesin, and histone variants: connecting the genome. AB - During the last decades our view of the genome organization has changed. We moved from a linear view to a looped view of the genome. It is now well established that inter- and intra-connections occur between chromosomes and play a major role in gene regulations. These interconnections are mainly orchestrated by the CTCF protein, which is also known as the "master weaver" of the genome. Recent advances in sequencing and genome-wide studies revealed that CTCF binds to DNA at thousands of sites within the human genome, providing the possibility to form thousands of genomic connection hubs. Strikingly, two histone variants, namely H2A.Z and H3.3, strongly co-localize at CTCF binding sites. In this article, we will review the recent advances in CTCF biology and discuss the role of histone variants H2A.Z and H3.3 at CTCF binding sites. PMID- 21970735 TI - Insulators. PMID- 21970736 TI - Association between maternal comorbidity and preterm birth by severity and clinical subtype: retrospective cohort study. AB - BACKGROUND: Preterm birth (PTB) is a major cause of infant morbidity and mortality, but the relationship between comorbidity and PTB by clinical subtype and severity of gestational age remains poorly understood. We evaluated associations between maternal comorbidities and PTB by clinical subtype and gestational age. METHODS: We conducted a retrospective cohort study of 1,329,737 singleton births delivered in hospitals in the province of Quebec, Canada, 1989 2006. PTB was classified by clinical subtype (medically indicated, preterm premature rupture of membranes (PPROM), spontaneous preterm labour) and gestational age (< 28, 28-31, 32-36 completed weeks). Odds ratios (OR) of PTB by clinical subtype for systemic and localized maternal comorbidities were estimated using polytomous logistic regression, adjusting for maternal age, grand multiparity, and period. Attributable fractions were calculated. RESULTS: PTB rates were higher among mothers with comorbidity (10.9%) compared to those without comorbidity (4.7%). Several comorbidities were associated with greater odds of medically indicated PTB compared with no comorbidity, but only comorbidities localized to the reproductive system were associated with spontaneous PTB. Drug dependence and mental disorders were strongly associated with PPROM and spontaneous PTBs across all gestational ages (OR > 2.0). At the population level, several major comorbidities (placental abruption, chorioamnionitis, oliogohydramnios, structural abnormality, cervical incompetence) were key contributors to all clinical subtypes of PTB, especially at < 32 weeks. Major systemic comorbidities (preeclampsia, anemia) were key contributors to PPROM and medically indicated PTBs. CONCLUSIONS: The relationship between comorbidity and clinical subtypes of PTB depends on gestational age. Prevention of PPROM and spontaneous PTB may benefit from greater attention to preeclampsia, anemia and comorbidities localized to the reproductive system. PMID- 21970737 TI - An access to the beta-anomer of 4'-thio-C-ribonucleosides: hydroboration of 1-C aryl- or 1-C-heteroaryl-4-thiofuranoid glycals and its regiochemical outcome. AB - We have developed a novel method for the synthesis of the beta-anomer of 4'-thio C-ribonucleosides from 3,5-O-(di-tert-butylsilylene)-4-thiofuranoid glycal. Palladium-catalyzed coupling of 1-tributylstannyl-4-thiofuranoid glycal with iodobenzene or a heteroaryl halide gave 1-C-phenyl- or 1-C-heteroaryl-glycals. Hydroboration of these glycals proceeded at the alpha-face, and subsequent alkaline hydrogen peroxide treatment of the resulting 2'-alpha-borane furnished the respective beta-anomer of 4'-thio-C-ribonucleosides. These results demonstrate that this synthetic method has a wider scope in terms of heterocyclic base structure. During this study, unexpected Markovnikov-oriented hydroboration has been observed to lead to the respective 1'-alpha-boranes. These 1'-boranes were converted into either the ring-opened structure or the 2'-deoxy derivatives depending upon their stability. PMID- 21970738 TI - Poor responders to controlled ovarian hyperstimulation for in vitro fertilisation (IVF). AB - The poor responder in assisted conception poses specific challenges to clinicians particularly as the aetiology remains poorly understood and there is, as yet, no consensus on the definition. Studies on this subject are very heterogeneous and therefore there is a lack of any good evidence base on how to deal with this difficult group of patients. As a result, much controversy exists on how to manage a poor responder in assisted conception and every new suggestion has proved contentious. The aim of this review is to provide an update and evaluation of the current evidence on the approach to management of the poor responder in assisted conception and to comment on the methods that have been suggested. PMID- 21970745 TI - Manifestation of a sellar hemangioblastoma due to pituitary apoplexy: a case report. AB - INTRODUCTION: Hemangioblastomas are rare, benign tumors occurring in any part of the nervous system. Most are found as sporadic tumors in the cerebellum or spinal cord. However, these neoplasms are also associated with von Hippel-Lindau disease. We report a rare case of a sporadic sellar hemangioblastoma that became symptomatic due to pituitary apoplexy. CASE PRESENTATION: An 80-year-old, otherwise healthy Caucasian woman presented to our facility with severe headache attacks, hypocortisolism and blurred vision. A magnetic resonance imaging scan showed an acute hemorrhage of a known, stable and asymptomatic sellar mass lesion with chiasmatic compression accounting for our patient's acute visual impairment. The tumor was resected by a transnasal, transsphenoidal approach and histological examination revealed a capillary hemangioblastoma (World Health Organization grade I). Our patient recovered well and substitutional therapy was started for panhypopituitarism. A follow-up magnetic resonance imaging scan performed 16 months postoperatively showed good chiasmatic decompression with no tumor recurrence. CONCLUSIONS: A review of the literature confirmed supratentorial locations of hemangioblastomas to be very unusual, especially within the sellar region. However, intrasellar hemangioblastoma must be considered in the differential diagnosis of pituitary apoplexy. PMID- 21970747 TI - Are predictive biomarkers of toxicity worth having? An economic model. AB - In this paper we model the cost-benefit of excluding populations at risk through predictive toxicity biomarkers and diagnostics. False positives/ negatives inherent in predictive markers and the frequency and nature of adverse events determine whether biomarkers are beneficial and economically viable. We present a model that takes these and other factors into account using data largely in line with real world cases. PMID- 21970746 TI - RAGE and ICAM-1 differentially control leukocyte recruitment during acute inflammation in a stimulus-dependent manner. AB - BACKGROUND: The receptor for advanced glycation endproducts, RAGE, is involved in the pathogenesis of many inflammatory conditions, which is mostly related to its strong activation of NF-kappaB but also due to its function as ligand for the beta2-integrin Mac-1. To further dissect the stimulus-dependent role of RAGE on leukocyte recruitment during inflammation, we investigated beta2-integrin dependent leukocyte adhesion in RAGE-/- and Icam1-/- mice in different cremaster muscle models of inflammation using intravital microscopy. RESULTS: We demonstrate that RAGE, but not ICAM-1 substantially contributes to N-formyl methionyl-leucyl-phenylalanine (fMLP)-induced leukocyte adhesion in TNF-alpha pretreated cremaster muscle venules in a Mac-1-dependent manner. In contrast, fMLP-stimulated leukocyte adhesion in unstimulated cremaster muscle venules is independent of RAGE, but dependent on ICAM-1 and its interaction with LFA-1. Furthermore, chemokine CXCL1-stimulated leukocyte adhesion in surgically prepared cremaster muscle venules was independent of RAGE but strongly dependent on ICAM-1 and LFA-1 suggesting a differential and stimulus-dependent regulation of leukocyte adhesion during inflammation in vivo. CONCLUSION: Our results demonstrate that RAGE and ICAM-1 differentially regulate leukocyte adhesion in vivo in a stimulus-dependent manner. PMID- 21970748 TI - Species difference in the regulation of cytochrome P450 2S1: lack of induction in rats by the aryl hydrocarbon receptor agonist PCB126. AB - CYP2S1 is an evolutionarily conserved, mainly extra-hepatic member of the CYP2 family and proposed to be regulated by the aryl hydrocarbon receptor (AhR). The present study explores AhR's regulation of CYP2S1 in male Sprague Dawley rats using PCB126 (3,3',4,4',5-pentachlorobiphenyl), the most potent AhR agonist among the PCBs. Additionally, CYP2S1 expression was examined after treatments with the classic CYP-inducers beta-naphthoflavone (beta-NF, AhR activator), phenobarbital (PB, CAR activator) and dexamethasone (Dex, PXR activator). CYP2S1 and CYP1A1/2, CYP1B1, CYP2B and CYP3A mRNAs were measured in liver, lung, spleen, stomach, kidney, and thymus at different time points. Constitutive CYP2S1 was expressed at comparable levels to other CYPs with the highest expression levels in stomach, kidney and lung. CYP2S1 mRNA was only non-significantly elevated by beta-NF in liver tissues. PCB126 did not increase CYP2S1 mRNA in any organ and at any time point examined despite a significant induction of CYP1 genes. PCB126 reduced CYP2S1 mRNA by 40% (not significant) from the 7th post-exposure day in thymus. PB and Dex had no effect on CYP2S1 mRNA levels. These observations show that in this model CYP2S1 is not, or only weakly, regulated by AhR and not induced by CAR or PXR activators. PMID- 21970749 TI - Immune-related disorders in families of children with inflammatory bowel disease- a prospective cohort study. AB - BACKGROUND: The aim of this paper was to examine the prevalence of immune-related disorders in families of children with inflammatory bowel disease (IBD) compared to those without IBD. METHODS: Children <=18 years of age presenting to the IBD clinic between September 2007 and August 2009 with an established diagnosis of IBD were recruited. Age and sex matched controls without IBD were recruited. The study was a single-centre prospective cohort study. Outcome measures were prevalence of immune-based/inflammatory diseases in families of both patients and controls. RESULTS: One hundred and eight children in each group were recruited. Asthma was the most frequently reported disease in families of the IBD patients (52.8%) and controls (46.3%). The prevalence of IBD in families of IBD patients was significantly higher than in those without IBD (OR 2.03, 95% CI 1.04-3.95). CONCLUSIONS: The prevalence of immune-based disorders, as a group, in families of children with IBD was not significantly higher when compared to children without IBD. PMID- 21970750 TI - Surface chemistry and annealing-driven interfacial changes in organic semiconducting thin films on silica surfaces. AB - Vibrational sum frequency generation (VSFG) spectroscopy was used in conjunction with steady-state IR spectroscopy, atomic force microscopy (AFM), and spectroscopic ellipsometry to characterize organic semiconductor thin films that were vapor deposited on silica- and trimethoxy(octadecyl)silane (ODTMS) functionalized silica surfaces. The growth of perylene derivative N,N'-dioctyl 3,4,9,10-perylenedicarboximide (PTCDI-C(8)) was found to proceed differently on simple glass slides relative to that of native oxide on silicon and fused quartz slides. VSFG was applied to these samples to isolate structural changes that occurred specifically at the buried interface between the organic semiconductor and the silica dielectric upon thermal annealing. A model was introduced to globally fit the imide carbonyl symmetric and asymmetric interfacial spectra that included contributions from both inner and outer interfaces. The fits to the VSFG data and AFM topographic images revealed significant reordering at the outer interface on all substrates upon thermal annealing. Within the model, the spectroscopic data reported that the inner interfacial PTCDI-C(8) monolayer reoriented to a more reclined phase on bare substrates after annealing but remained essentially unchanged on ODTMS monolayers. Electrical characterization of PTCDI-C(8) field-effect transistors indicated that electron mobilities were higher on bare substrate devices but could be improved by a factor of 2 on both surface types by thermal annealing. The mobility effects were attributed to the annealing-driven coalescence of PTCDI-C(8) grain boundaries. Consistent with previous structural reports, the molecular rearrangements of the first monolayer of PTCDI-C(8) on bare substrates that were reported by VSFG spectroscopy had a noticeable impact on the device performance. PMID- 21970763 TI - Mechanism of recombination of the P+H(A)- radical pair in mutant Rhodobacter sphaeroides reaction centers with modified free energy gaps between P+B(A)- and P+H(A)-. AB - The kinetics of recombination of the P(+)H(A)(-) radical pair were compared in wild-type reaction centers from Rhodobacter sphaeroides and in seven mutants in which the free energy gap, DeltaG, between the charge separated states P(+)B(A)( ) and P(+)H(A)(-) was either increased or decreased. Five of the mutant RCs had been described previously, and X-ray crystal structures of two newly constructed complexes were determined by X-ray crystallography. The charge recombination reaction was accelerated in all mutants with a smaller DeltaG than in the wild type, and was slowed in a mutant having a larger DeltaG. The free energy difference between the state P(+)H(A)(-) and the PH(A) ground state was unaffected by most of these mutations. These observations were consistent with a model in which the P(+)H(A)(-) -> PH(A) charge recombination is thermally activated and occurs via the intermediate state P(+)B(A)(-), with a mean rate related to the size of the DeltaG between the states P(+)B(A)(-) and P(+)H(A)(-) and not the DeltaG between P(+)H(A)(-) and the ground state. A more detailed analysis of charge recombination in the mutants showed that the kinetics of the reaction were multiexponential, and characterized by ~0.5, ~1-3, and 7-17 ns lifetimes, similar to those measured for wild-type reaction centers. The exact lifetimes and relative amplitudes of the three components were strongly modulated by the mutations. Two models were considered in order to explain the observed multiexponentiality and modulation, involving heterogeneity or relaxation of P(+)H(A)(-) states, with the latter model giving a better fit to the experimental results. PMID- 21970764 TI - Exploring the ellipsoidal and core-shell geometries of copper-seamed C alkylpyrogallol[4]arene nanocapsules in solution. AB - Small-angle neutron scattering (SANS) studies were used to probe the stability and geometry of copper-seamed C-alkylpyrogallol[4]arene (PgC(n)Cu; n = 11, 13, 17) hexamers in solution. Novel structural features are observed at chain lengths greater than 10 in both solid and solution phase. Scattering data for the PgC(11)Cu and PgC(13)Cu in chloroform fitted as core-shell spheres with a total spherical radius of about 22.7 and 22.9 A respectively. On the other hand, the scattering curve for the PgC(17)Cu hexamer at both 1% and 5% mass fractions in o xylene did not fit as a discrete sphere but rather as a uniform ellipsoid. The geometric dimensions of the ellipsoid radii are 24 A along the minor axis and 115 A along the major axis. It is expected that an individual hexamer with heptadecyl chains would exhibit a uniform radius of ca. 24 A. However, an approximate ratio of 1:5 between radii lengths for the minor axis and major axis is consistent with interpenetration of the heptadceyl chains of adjacent hexamers to form a single ellipsoidal assembly. PMID- 21970765 TI - A multibody knee model with discrete cartilage prediction of tibio-femoral contact mechanics. AB - Combining musculoskeletal simulations with anatomical joint models capable of predicting cartilage contact mechanics would provide a valuable tool for studying the relationships between muscle force and cartilage loading. As a step towards producing multibody musculoskeletal models that include representation of cartilage tissue mechanics, this research developed a subject-specific multibody knee model that represented the tibia plateau cartilage as discrete rigid bodies that interacted with the femur through deformable contacts. Parameters for the compliant contact law were derived using three methods: (1) simplified Hertzian contact theory, (2) simplified elastic foundation contact theory and (3) parameter optimisation from a finite element (FE) solution. The contact parameters and contact friction were evaluated during a simulated walk in a virtual dynamic knee simulator, and the resulting kinematics were compared with measured in vitro kinematics. The effects on predicted contact pressures and cartilage-bone interface shear forces during the simulated walk were also evaluated. The compliant contact stiffness parameters had a statistically significant effect on predicted contact pressures as well as all tibio-femoral motions except flexion-extension. The contact friction was not statistically significant to contact pressures, but was statistically significant to medial lateral translation and all rotations except flexion-extension. The magnitude of kinematic differences between model formulations was relatively small, but contact pressure predictions were sensitive to model formulation. The developed multibody knee model was computationally efficient and had a computation time 283 times faster than a FE simulation using the same geometries and boundary conditions. PMID- 21970766 TI - Tumor accumulation of NIR fluorescent PEG-PLA nanoparticles: impact of particle size and human xenograft tumor model. AB - Cancer therapies are often terminated due to serious side effects of the drugs. The cause is the nonspecific distribution of chemotherapeutic agents to both cancerous and normal cells. Therefore, drug carriers which deliver their toxic cargo specific to cancer cells are needed. Size is one key parameter for the nanoparticle accumulation in tumor tissues. In the present study the influence of the size of biodegradable nanoparticles was investigated in detail, combining in vivo and ex vivo analysis with comprehensive particle size characterizations. Polyethylene glycol-polyesters poly(lactide) block polymers were synthesized and used for the production of three defined, stable, and nontoxic near-infrared (NIR) dye-loaded nanoparticle batches. Size analysis based on asymmetrical field flow field fractionation coupled with multiangle laser light scattering and photon correlation spectroscopy (PCS) revealed narrow size distribution and permitted accurate size evaluations. Furthermore, this study demonstrates the constraints of particle size data only obtained by PCS. By the multispectral analysis of the Maestro in vivo imaging system the in vivo fate of the nanoparticles next to their accumulation in special red fluorescent DsRed2 expressing HT29 xenografts could be followed. This simultaneous imaging in addition to confocal microscopy studies revealed information about the accumulation characteristics of nanoparticles inside the tumor tissues. This knowledge was further combined with extended size-dependent fluorescence imaging studies at two different xenograft tumor types, the HT29 (colorectal carcinoma) and the A2780 (ovarian carcinoma) cell lines. The combination of two different size measurement methods allowed the characterization of the dependence of nanoparticle accumulation in the tumor on even rather small differences in the nanoparticle size. While two nanoparticle batches (111 and 141 nm in diameter) accumulated efficiently in the human xenograft tumor tissue, the slightly bigger nanoparticles (diameter 166 nm) were rapidly eliminated by the liver. PMID- 21970767 TI - Fast and protecting-group-free synthesis of (+/-)-subincanadine C. AB - The first total synthesis of (+/-)-subincanadine C has been accomplished in a protecting-group-free fashion. This pentacyclic indole alkaloid was synthesized in six steps from the known intermediate 4, featuring Ni(COD)(2)-mediated intramolecular Michael addition as a key transformation. PMID- 21970768 TI - Design, synthesis, and biological activities of arylmethylamine substituted chlorotriazine and methylthiotriazine compounds. AB - Heterocyclic rings were introduced into the core structure of s-triazine to design and synthesize a series of novel triazines containing arylmethylamino moieties. These compounds were characterized by using spectroscopic methods and elemental analysis. Their herbicidal, insecticidal, fungicidal, and antitumor activities were evaluated. Most of these compounds exhibited good herbicidal activity, especially against the dicotyledonous weeds, and compound F8 was almost at the same level as the control compound atrazine. Their structure-activity relationships were discussed. At the same time, some triazines had interesting fungicidal and insecticidal activities, of which F4 exhibited 100% efficacy against Puccinia triticina even at 20 ppm, and F5 showed Lepidopteran-specific activity in both leaf-piece and artificial diet assays. Moreover, these compounds showed antitumor activities against leukemia HL-60 cell line and lung adenocarcinoma A-549 cell line. PMID- 21970769 TI - Clinical toxicology of newer recreational drugs. AB - INTRODUCTION: Novel synthetic 'designer' drugs with stimulant, ecstasy-like (entactogenic) and/or hallucinogenic properties have become increasingly popular among recreational drug users in recent years. The substances used change frequently in response to market trends and legislative controls and it is an important challenge for poisons centres and clinical toxicologists to remain updated on the pharmacological and toxicological effects of these emerging agents. AIMS: To review the available information on newer synthetic stimulant, entactogenic and hallucinogenic drugs, provide a framework for classification of these drugs based on chemical structure and describe their pharmacology and clinical toxicology. METHODS: A comprehensive review of the published literature was performed using PUBMED and Medline databases, together with additional non peer reviewed information sources, including books, media reports, government publications and internet resources, including drug user web forums. EPIDEMIOLOGY: Novel synthetic stimulant, entactogenic or hallucinogenic designer drugs are increasingly available to users as demonstrated by user surveys, poisons centre calls, activity on internet drug forums, hospital attendance data and mortality data. Some population sub groups such as younger adults who attend dance music clubs are more likely to use these substances. The internet plays an important role in determining the awareness of and availability of these newer drugs of abuse. CLASSIFICATION: Most novel synthetic stimulant, entactogenic or hallucinogenic drugs of abuse can be classified according to chemical structure as piperazines (e.g. benzylpiperazine (BZP), trifluoromethylphenylpiperazine), phenethylamines (e.g. 2C or D-series of ring-substituted amfetamines, benzodifurans, cathinones, aminoindans), tryptamines (e.g. dimethyltryptamine, alpha-methyltryptamine, ethyltryptamine, 5-methoxy-alphamethyltryptamine) or piperidines and related substances (e.g. desoxypipradrol, diphenylprolinol). Alternatively classification may be based on clinical effects as either primarily stimulant, entactogenic or hallucinogenic, although most drugs have a combination of such effects. CLINICAL TOXICOLOGY: Piperazines, phenethylamines, tryptamines and piperidines have actions at multiple central nervous system (CNS) receptor sites, with patterns of effects varying between agents. Predominantly stimulant drugs (e.g. benzylpiperazine, mephedrone, naphyrone, diphenylprolinol) inhibit monoamine (especially dopamine) reuptake and are characteristically associated with a sympathomimetic toxidrome. Entactogenic drugs (e.g. phenylpiperazines, methylone) provoke central serotonin release, while newer hallucinogens (e.g. 5 methoxy-N,N-diisopropyltryptamine (5-MeO-DiPT), 2,5-dimethoxy-4-bromoamfetamine (DOB)) are serotonin receptor agonists. As a result, serotoninergic effects predominate in toxicity. CONCLUSIONS: There are limited reliable data to guide clinicians managing patients with toxicity due to these substances. The harms associated with emerging recreational drugs are not fully documented, although it is clear that they are not without risk. Management of users with acute toxic effects is pragmatic and primarily extrapolated from experience with longer established stimulant or hallucinogenic drugs such as amfetamines, 3,4 methylenedioxymethamfetamine (MDMA) and lysergic acid diethylamide (LSD). PMID- 21970770 TI - Earlier recognition of nephrotoxicity using novel biomarkers of acute kidney injury. AB - CONTEXT: A broad range of drugs and chemicals are capable of evoking acute kidney injury, which is conventionally determined by rising serum creatinine concentrations. However there are important limitations to this approach, and there has been interest in alternative biomarkers that might provide a more sensitive and rapid means of detecting acute kidney injury. Most of the available clinical data have thus far been ascertained in patients requiring critical care or with acute sepsis. However, if a sensitive indicator of acute kidney injury were developed, then this could provide a significantly improved means of detecting the effects of acute drug or toxin exposure. OBJECTIVE: To review the available data concerning potential biomarkers of acute kidney injury and to assess their relative strengths and weaknesses in comparison to existing methods based on serum creatinine concentrations. A large number of possible biomarkers have been proposed. Evidence for individual biomarkers is reviewed with a particular emphasis on those with potential application in clinical toxicology. Where available, comparative data are presented. METHODS: There were 236 papers identified using Medline, Embase, and Google Scholar databases, of which 52 were considered directly relevant. CREATININE: Creatinine is subject to glomerular filtration and, to a lesser extent tubular secretion. Serum concentrations are an insensitive marker of acute kidney injury, and the speed of an increase from baseline depends on the magnitude of the acute injury and pre-existing kidney functional reserve. A wide range of inter-individual concentrations means that single time-point determinations are difficult to interpret, and acute kidney injury may not manifest as a detectable increase in serum creatinine concentrations until at least 24-48 h after the primary insult. KIDNEY ENZYMES: Enzymes are often localised to specific anatomical locations, and acute injury may cause a detectable increase in urinary activity due to up-regulated activity or leakage due to cell membrane disruption. Key examples include gamma-glutamyl transpeptidase (GGT), glutathione-S-transferase (GST), and N-acetyl glucosaminidase (NAG), which are found predominantly in the proximal tubule and urinary enzyme activity increases after acute exposure to heavy metals and other nephrotoxins. NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN: Neutrophil gelatinase associated lipocalin (NGAL) is expressed by renal tubular epithelium, and a rise in urinary concentrations may provide an indicator of acute renal injury caused by any one of a broad range of provoking factors that is detectable before a rise in serum creatinine concentrations. CYSTATIN C: Serum and urinary cystatin C concentrations are closely related to kidney function and, for example, in acute tubular necrosis allow better prediction of the need for renal replacement therapy than serum creatinine concentrations. KIDNEY INJURY MOLECULE 1: Kidney injury molecule 1 (KIM-1) is expressed in the proximal tubule in the setting of acute ischaemia. For example, urinary KIM-1 concentrations becomes detectable within 24 h of acute tubular necrosis. Urinary KIM-1 expression may be detected after exposure to a variety of nephrotoxic agents, even when serum creatinine concentrations do not increase, and this has been accepted by regulatory authorities as a sensitive biomarker of acute kidney injury during early drug development. CONCLUSIONS: Novel biomarkers appear capable of offering a more sensitive means of detecting acute kidney injury than existing approaches. Certain of these allow discrimination between the various mechanisms and anatomical site of acute injury. Ultimately, clinical assessment might incorporate a panel of different biomarkers, each informing on the integrated aspects of glomerular, tubular and interstitial function. Presence of biomarkers may in some cases detect mild or transient renal dysfunction that is presently undetected, and the clinical relevance needs further exploration. Whilst many potentially useful biomarkers have been proposed, comparatively few clinical data exist to support their validity in routine practice. Further prospective clinical studies are required to examine the validity of biomarkers after acute drug or toxin exposure, and to establish whether they might offer improved clinical outcomes in the setting of clinical toxicology. PMID- 21970771 TI - Fatty acids antagonize bupivacaine-induced I(Na) blockade. AB - Theories regarding the mechanism of intravenous fat emulsion for bupivacaine cardiotoxicity include creation of an intravascular lipid sink into which the cardiotoxic drug is sequestered, an improvement of impaired cardiac metabolism, and restoration of cardiomyocyte function by increasing intracellular calcium. However, work in this area is inconclusive and a more mechanistic explanation is desirable. We used a heterologous expression system (HEK-293 cells) and voltage clamp techniques to study the electrophysiologic effects of bupivacaine, polyunsaturated, and saturated fatty acids on sodium current (I(Na)) in stable cell lines expressing human cardiac sodium channels. Linolenic (polyunsaturated) and stearic (saturated) fatty acids were selected for study as they are components of commonly used lipid infusions. Bupivacaine-induced significant tonic and use dependent I(Na) block, as expected. Linolenic and stearic fatty acids directly modulated I(Na), inducing primarily tonic block. Greater block was seen with linolenic acid as compared with stearic acid. Simultaneous exposure to bupivacaine and fatty acids reduced both the tonic and use dependent block compared with bupivacaine alone. Reduction of bupivacaine-induced I(Na) block was greatest in cells treated with linolenic acid. These results suggest that the salutary effects of intravenous fat emulsion may be, in part, due to a direct modulatory effect of fatty acids on cardiac sodium channels. PMID- 21970772 TI - Prognostic significance of arterial blood gas analysis in the early evaluation of paraquat poisoning patients. AB - OBJECTIVE: To examine the utility of arterial blood gas analysis (ABG) in early evaluation of prognosis in paraquat poisoning. METHODS: Our aim was to summarize the case data of 138 patients poisoned with oral paraquat treated in the Emergency Department of 307 Hospital of the Chinese People's Liberation Army from June 2009 to Sept. 2010, and analyze the correlations between various indices of arterial blood gas analysis (including pH, PO(2), PCO(2), base excess [BE], HCO(3)(-)) to prognosis and blood PQ concentration of patients presenting within 24 h after taking paraquat. RESULTS: PCO(2), HCO(3)(-) and BE values in deceased patients were significantly lower than those in surviving patients, p values 0.0003, <0.0001, <0.0001; PCO(2), HCO(3)(-) and BE values in patients who died in < 3 d were significantly lower than those in those who died in 3-7 d and 7 d after taking paraquat (p < 0.0001). The results of Cox Regression Analysis showed that there was correlation between paraquat amount, blood paraquat concentration and BE values and patients' survival time; the larger the absolute BE value was, the higher the death rate. Nevertheless, there were no correlations between early pH or PO(2) and prognosis in these patients. CONCLUSION: BE values may be a reliable index in early evaluation of prognosis in paraquat poisoning. PMID- 21970773 TI - One collective case of type A foodborne botulism in Corsica. AB - Foodborne botulism is rare in 21st century Western Europe. The purpose of this report is to describe a collective case of type A botulism caused by ingestion of artisanal-produced food (canned green beans and/or salted roast pork). Five of the seven persons who shared the meal presented signs of severe intoxication leading to the fatal respiratory failure in one 18-year-old girl. Three patients required mechanical ventilation for durations ranging from 37 to 78 days and developed severe infectious, respiratory and/or psychiatric complications. In 4 out of the 5 patients, trivalent antitoxin was administered between days 2 and 7 but did not avoid the need for long-term intubation/mechanical ventilation. Treatment with 3,4-diaminopyridine was ineffective in the 26-year-old man who required long-term breathing assistance. This case of collective foodborne botulism illustrates the potential severity of this hazard. PMID- 21970774 TI - Hemolysis and hemolytic uremic syndrome following five-fold N-acetylcysteine overdose. AB - CONTEXT: Intravenous acetylcysteine (AcetadoteTM in the US) is the treatment of choice for acute acetaminophen poisoning in most of the world. However, the complicated dosing regimen is prone to errors in preparation and administration. CASE REPORT: A 21 year-old woman (70 kg) took an overdose of acetaminophen and ethanol. Her serum acetaminophen concentration was > 200 mg/L. Acetylcysteine infusion was ordered. Due to misreading of the columns in the table in the AcetadoteTM package insert, she received a five-fold overdose of 52.5 g of acetylcysteine in 500 mL over 1 h and then 17.5 g of acetylcysteine in 500 mL to run over 4 h. The dose error was detected 20 min into the second infusion. Her acetaminophen concentration fell quickly, and her highest transaminase concentrations occurred day 2. Her hemoglobin and hematocrit quickly dropped from 14.8 g/dL and 44.0% on admission to 6.2 g/dL and 17.3% on day 7. Subsequently she developed hematuria and a rapidly rising serum creatinine. She was transferred to a tertiary care hospital, where she underwent hemodialysis every two days for two weeks, transfusions of packed red blood cells, and plasmapheresis until hematologic testing ruled out thrombotic thrombocytopenia purpura. DISCUSSION: A five-fold overdose of acetylcysteine was followed by unexpected hemolysis and acute renal failure. The mechanism of hemolysis after acetylcysteine overdose is unclear. A simpler infusion regimen with standard concentrations would prevent a similar error. PMID- 21970776 TI - A novel use of naloxone as a treatment for eucalyptus oil induced central nervous system depression. PMID- 21970775 TI - Severe toxicity following synthetic cannabinoid ingestion. AB - OBJECTIVE: To report a case of seizures and supraventricular tachycardia (SVT) following confirmed synthetic cannabinoid ingestion. BACKGROUND: Despite widespread use of legal synthetic cannabinoids, reports of serious toxicity following confirmed use of synthetic cannabinoids are rare. We report severe toxicity including seizures following intentional ingestion of the synthetic cannabinoid JWH-018 and detail confirmation by laboratory analysis. CASE REPORT: A healthy 48 year old man had a generalized seizure within thirty minutes of ingesting an ethanol mixture containing a white powder he purchased from the Internet in an attempt to get high. Seizures recurred and abated with lorazepam. Initial vital signs were: pulse, 106/min; BP, 140/88 mmHg; respirations, 22/min; temperature, 37.7 degrees C. A noncontrast computed tomography of the brain and EEG were negative, and serum chemistry values were normal. The blood ethanol concentration was 3.8 mg/dL and the CPK 2,649 U/L. Urine drug screening by EMIT was negative for common drugs of abuse, including tetrahydrocannabinol. On hospital day 1, he developed medically refractory SVT. The patient had no further complications and was discharged in his normal state of health 10 days after admission. The original powder was confirmed by gas chromatography mass spectrometry to be JWH-018, and a primary JWH-018 metabolite was detected in the patient's urine (200 nM) using liquid chromatography tandem mass spectrometry. DISCUSSION: Synthetic cannabinoids are legal in many parts of the world and easily obtained over the Internet. Data on human toxicity are limited and real time confirmatory testing is unavailable to clinicians. The potential for toxicity exists for users mistakenly associating the dose and side effect profiles of synthetic cannabinoids to those of marijuana. CONCLUSION: Ingestion of JWH-018 can produce seizures and tachyarrhythmias. Clinicians, lawmakers, and the general public need to be aware of the potential for toxicity associated with synthetic cannabinoid use. PMID- 21970777 TI - Video clip transfer of radiological images using a mobile telephone in emergency neurosurgical consultations (3G Multi-Media Messaging Service). AB - BACKGROUND: The purpose of this study was to validate and assess the accuracy and usefulness of sending short video clips in 3gp file format of an entire scan series of patients, using mobile telephones running on 3G-MMS technology, to enable consultation between junior doctors in a neurosurgical unit and the consultants on-call after office hours. METHOD: A total of 56 consecutive patients with acute neurosurgical problems requiring urgent after-hours consultation during a 6-month period, prospectively had their images recorded and transmitted using the above method. The response to the diagnosis and the management plan by two neurosurgeons (who were not on site) based on the images viewed on a mobile telephone were reviewed by an independent observer and scored. In addition to this, a radiologist reviewed the original images directly on the hospital's Patients Archiving and Communication System (PACS) and this was compared with the neurosurgeons' response. RESULTS: Both neurosurgeons involved in this study were in complete agreement with their diagnosis. The radiologist disagreed with the diagnosis in only one patient, giving a kappa coefficient of 0.88, indicating an almost perfect agreement. CONCLUSION: The use of mobile telephones to transmit MPEG video clips of radiological images is very advantageous for carrying out emergency consultations in neurosurgery. The images accurately reflect the pathology in question, thereby reducing the incidence of medical errors from incorrect diagnosis, which otherwise may just depend on a verbal description. PMID- 21970778 TI - Intramedullary metastasis in a case of vermian medulloblastoma. AB - Medulloblastoma is one of the commonest primary CNS malignancies in children. Leptomeningeal dissemination and distant metastasis have been associated with medulloblastoma, but intramedullary metastases are very rare. CSF cytology and contrast-enhanced MRI are the main modalities used to diagnose leptomeningeal dissemination. However, intramedullary metastases are best picked up with contrast-enhanced axial sequences on MR imaging. In this report, a patient with medulloblastoma who developed intramedullary metastasis is described. The role of imaging and CSF cytology in diagnosing the spread along the CSF pathways is reviewed. Allusions are made to the possible mechanism of intramedullary metastasis in these tumors. PMID- 21970779 TI - Detection of ophthalmic artery occlusion by visual evoked potential during carotid-ophthalmic artery aneurysm clipping. AB - We report an intriguing case of carotid-ophthalmic artery (OA) aneurysm surgery, in which the visual evoked potential (VEP) wave diminished during temporary OA occlusion. VEP waves suddenly disappeared after clipping, and repositioning of the clip restored blood flow to the OA and recovered the VEP wave. PMID- 21970780 TI - Management of delayed oesophagus perforation and osteomyelitis after cervical spine surgery: review of the literature. AB - Oesophagus perforation is a possible complication of anterior cervical spine surgery, which generally occurs during the first postoperative days. Delayed perforation is very rare and its management remains controversial. We report the successful management of a delayed oesophagus perforation associated with an osteomyelitis. PMID- 21970781 TI - Ventriculostomy for acute hydrocephalus in critically ill patients on the ICU- outcome analysis of two different procedures. AB - INTRODUCTION: Burr-hole trephine and insertion of an external ventricular drainage (EVD) is a common procedure in neurosurgical practice. In critically ill patients, the transport to the operating room, OR represents a major risk. Thus, the burr-hole trephine and implantation of an EVD is frequently performed on the Intensive Care Unit (ICU). Since 2004, we have applied two different procedures: the conventional method with a mechanical compressed air or an electric drill, and an alternative method with a manual twist drill, including fixation of the EVD in a skull screw (Bolt Kit, Raumedic AG, Germany). This study was designed to evaluate the outcome of both surgical procedures. PATIENTS AND METHOD: In this retrospective analysis we included 166 consecutive patients with acute hydrocephalus due to intracranial hemorrhage that had been operated at our neurosurgical ICU in a six years interval. We reviewed the charts for gender and age, kind of surgical procedure, cerebrospinal fluid (CSF)-infections, duration of drainage, attempts of insertions, wound infections, misplacement rate, post surgical hemorrhages, revisions, comorbidities and shunt-dependency. RESULTS: In 122 patients we applied the Bolt Kit System, in 44 patients the conventional method was performed. We found a significantly lower rate of CSF-infections and significantly fewer attempts of insertions in the Bolt Kit group (p = 0.002 and p = 0.001, respectively). The rate of wound infections, misplacement, revisions, shunt-dependency and the post-surgical hemorrhages did not differ significantly. DISCUSSION: Our data indicate that the manual drill and the skull screw are safe and feasible tools in the treatment of acute hydrocephalus. Presumably, the direct skin contact is causative for the higher rate of CSF-infections when the conventional method is performed. The skull screw guides the EVD into the ventricle without skin contact. The lower number of insertions needed may be due to the fact that the skull screw allows just one trajectory for the insertion of the EVD. PMID- 21970782 TI - Bilateral cerebellopontine angle lesions not always NF2: diagnostic pitfall. AB - Bilateral internal auditory canal (IAC) tumours are almost exclusively associated with bilateral vestibular schwannomas, and there is very little, if anything, that can mimic this appearance. We present a very rare case of a 75-year-old gentleman who initially presented with bilateral IAC tumours and later diagnosed as an isolated primary CNS myeloma without systemic involvement. This is a very rare presentation and has important diagnostic and therapeutic implications. He was treated with a combination of lenalidomide and dexamethasone. The treatment was well tolerated but with limited response. Although rare, metastasis should be considered as a differential diagnosis of IAC lesions. PMID- 21970783 TI - Choroid plexus tumors in pediatric patients. AB - OBJECTIVE: Choroid plexus tumors are rare intraventricular tumors, accounting for less than 1% of all intracranial tumors and 2-4% of brain tumors in children. The authors present their experience in the management of these lesions, and a review of the literature is performed. METHODS: We retrospectively analyzed the outcome of pediatric patients with choroid plexus tumors treated with surgical resection. The patients' charts were reviewed for demographic data, clinical presentation, surgical therapy and follow-up. RESULTS: This study involves 18 consecutive choroid plexus tumors: 14 papillomas, 2 atypical papillomas and 2 carcinomas. The tumor was located in the lateral ventricles (12), the fourth ventricle (4) and the third ventricle (2). The mean age at presentation was 4.6 years. Surgical resection was performed in all cases and no patients died perioperatively. Survival rate of papilloma patients was 100% without evidence of recurrent disease (mean follow-up for 73 months). Survival rate of carcinoma patients was 50% (mean follow-up for 23.5 months). One carcinoma patient died of disseminated disease 13 months after surgery. The functional outcome in long-term survivors after papilloma surgery was excellent. Postoperative extraventricular drainage (EVD) was performed in 12 patients. Five patients (27.8%) had persistent hydrocephalus after tumor resection and required a ventriculoperitoneal shunt. CONCLUSION: Choroid plexus papilloma is a surgically curable disease. Postoperative EVD was considered effective in lowering the rate of shunt requirement through releasing the blood-tinged CSF and small particles of tumor residue. PMID- 21970785 TI - A tale of two isomerases: compact versus extended active sites in ketosteroid isomerase and phosphoglucose isomerase. AB - Understanding the catalytic efficiency and specificity of enzymes is a fundamental question of major practical and conceptual importance in biochemistry. Although progress in biochemical and structural studies has enriched our knowledge of enzymes, the role in enzyme catalysis of residues that are not nearest neighbors of the reacting substrate molecule is largely unexplored experimentally. Here computational active site predictors, THEMATICS and POOL, were employed to identify functionally important residues that are not in direct contact with the reacting substrate molecule. These predictions then guided experiments to explore the active sites of two isomerases, Pseudomonas putida ketosteroid isomerase (KSI) and human phosphoglucose isomerase (PGI), as prototypes for very different types of predicted active sites. Both KSI and PGI are members of EC 5.3 and catalyze similar reactions, but they represent significantly different degrees of remote residue participation, as predicted by THEMATICS and POOL. For KSI, a compact active site of mostly first-shell residues is predicted, but for PGI, an extended active site in which residues in the first, second, and third layers around the reacting substrate are predicted. Predicted residues that have not been previously tested experimentally were investigated by site-directed mutagenesis and kinetic analysis. In human PGI, single-point mutations of the predicted second- and third-shell residues K362, H100, E495, D511, H396, and Q388 show significant decreases in catalytic activity relative to that of the wild type. The results of these experiments demonstrate that, as predicted, remote residues are very important in PGI catalysis but make only small contributions to catalysis in KSI. PMID- 21970786 TI - Correlation between plasma levels of radical scavengers and hearing threshold among elderly subjects with age-related hearing loss. AB - CONCLUSION: Low plasma melatonin is significant in the development of high frequency hearing loss (HL) among the elderly. OBJECTIVE: To determine the correlation between hearing threshold and the plasma melatonin and ascorbic acid (vitamin C). METHODS: This was a cross-sectional study involving 126 apparently healthy elderly subjects, 59 males and 67 females, aged >60 years. Subjects underwent pure tone audiometry and plasma melatonin and vitamin C were assayed using high-performance liquid chromatography. RESULTS: The mean +/- SD of plasma melatonin among the subjects with normal hearing (NH) (0-30 dB) and those with HL in the speech frequencies was 18.3 +/- 3.6 MUg/L and 16.4 +/- 4.7 MUg/L, respectively. In the high frequencies the values were 17.7 +/- 6.2 MUg/L and 13.1 +/- 6.4 MUg/L for NH and HL, respectively. For vitamin C, the mean +/- SD among subjects with NH and those with HL in the speech frequencies were 1.2 +/- 0.2 MUg/L and 1.0 +/- 0.1 MUg/L, respectively. In the high frequencies, the values were 1.0 +/- 0.2 MUg/L and 0.9 +/- 0.3 MUg/L for NH and HL, respectively. Among subjects with high frequency HL, Spearman's correlation revealed significant correlation between increasing hearing threshold and melatonin (correlation coefficient = -0.30, p = 0.01), but not for vitamin C (correlation coefficient = 0.12, p = 0.22). Linear regression, adjusting for age, still revealed significant correlation between the melatonin (correlation coefficient = -0.03, p = 0.00) and hearing threshold in the high frequencies. PMID- 21970787 TI - Recovery from adaptation of the action potential in idiopathic sudden sensorineural hearing loss investigated using a paired-click stimulation paradigm. AB - CONCLUSION: We studied the compound action potential (AP) recovery from adaptation (AP recovery) in idiopathic sensorineural hearing loss (iSSNHL). Abnormal AP recovery was demonstrated in 15 of 45 patients, consisting of increased recovery (iR) over the normal range in 11 ears and decreased recovery (dR) under the normal range in 4 ears. The mechanisms for occurrence and clinical significance of these phenomena are currently unknown. OBJECTIVES: The purpose of this study was to investigate the pathologic features of AP recovery in iSSNHL. METHODS: Forty-five subjects with iSSNHL were enrolled and 18 normal-hearing subjects participated to assess the normal range of AP recovery. Equilevel paired clicks with inter-click interval from 5 to 100 ms were applied as acoustic stimuli. RESULTS: Eleven ears with iR and four ears with dR were found. The audiogram patterns of 11 iR and 4 dR ears exhibited 10 flat types, 3 high frequency loss types, and 2 low frequency loss types. Only 2 of 11 subjects with iR ears and 0 of 4 with dR ears complained of vertigo. No significant difference was observed in the comparison between AP threshold and hearing level of iR with those of normal recovery (nR) within the normal range. PMID- 21970788 TI - Architecture of a consent management suite and integration into IHE-based Regional Health Information Networks. AB - BACKGROUND: The University Hospital Heidelberg is implementing a Regional Health Information Network (RHIN) in the Rhine-Neckar-Region in order to establish a shared-care environment, which is based on established Health IT standards and in particular Integrating the Healthcare Enterprise (IHE). Similar to all other Electronic Health Record (EHR) and Personal Health Record (PHR) approaches the chosen Personal Electronic Health Record (PEHR) architecture relies on the patient's consent in order to share documents and medical data with other care delivery organizations, with the additional requirement that the German legislation explicitly demands a patients' opt-in and does not allow opt-out solutions. This creates two issues: firstly the current IHE consent profile does not address this approach properly and secondly none of the employed intra- and inter-institutional information systems, like almost all systems on the market, offers consent management solutions at all. Hence, the objective of our work is to develop and introduce an extensible architecture for creating, managing and querying patient consents in an IHE-based environment. METHODS: Based on the features offered by the IHE profile Basic Patient Privacy Consent (BPPC) and literature, the functionalities and components to meet the requirements of a centralized opt-in consent management solution compliant with German legislation have been analyzed. Two services have been developed and integrated into the Heidelberg PEHR. RESULTS: The standard-based Consent Management Suite consists of two services. The Consent Management Service is able to receive and store consent documents. It can receive queries concerning a dedicated patient consent, process it and return an answer. It represents a centralized policy enforcement point. The Consent Creator Service allows patients to create their consents electronically. Interfaces to a Master Patient Index (MPI) and a provider index allow to dynamically generate XACML-based policies which are stored in a CDA document to be transferred to the first service. Three workflows have to be considered to integrate the suite into the PEHR: recording the consent, publishing documents and viewing documents. CONCLUSIONS: Our approach solves the consent issue when using IHE profiles for regional health information networks. It is highly interoperable due to the use of international standards and can hence be used in any other region to leverage consent issues and substantially promote the use of IHE for regional health information networks in general. PMID- 21970789 TI - Transfer of newborns to neonatal care unit: a registry based study in Northern Tanzania. AB - BACKGROUND: Reduction in neonatal mortality has been slower than anticipated in many low income countries including Tanzania. Adequate neonatal care may contribute to reduced mortality. We studied factors associated with transfer of babies to a neonatal care unit (NCU) in data from a birth registry at Kilimanjaro Christian Medical Centre (KCMC) in Tanzania. METHODS: A total of 21 206 singleton live births registered from 2000 to 2008 were included. Multivariable analysis was carried out to study neonatal transfer to NCU by socio-demographic factors, pregnancy complications and measures of the condition of the newborn. RESULTS: A total of 3190 (15%) newborn singletons were transferred to the NCU. As expected, neonatal transfer was strongly associated with specific conditions of the baby including birth weight above 4000 g (relative risk (RR) = 7.2; 95% confidence interval (CI) 6.5-8.0) or below 1500 g (RR = 3.0; 95% CI: 2.3-4.0), five minutes Apgar score less than 7 (RR = 4.0; 95% CI: 3.4-4.6), and preterm birth before 34 weeks of gestation (RR = 1.8; 95% CI: 1.5-2.1). However, pregnancy- and delivery related conditions like premature rupture of membrane (RR = 2.3; 95% CI: 1.9 2.7), preeclampsia (RR = 1.3; 95% CI: 1.1-1.5), other vaginal delivery (RR = 2.2; 95% CI: 1.7-2.9) and caesarean section (RR = 1.9; 95% CI: 1.8-2.1) were also significantly associated with transfer. Birth to a first born child was associated with increased likelihood of transfer (relative risk (RR) 1.4; 95% CI: 1.2-1.5), while the likelihood was reduced (RR = 0.5; 95% CI: 0.3-0.9) when the father had no education. CONCLUSIONS: In addition to strong associations between neonatal transfer and classical neonatal risk factors for morbidity and mortality, some pregnancy-related and demographic factors were predictors of neonatal transfer. Overall, transfer was more likely for babies with signs of poor health status or a complicated pregnancy. Except for a possibly reduced use of transfer for babies of non-educated fathers and a high transfer rate for first born babies, there were no signs that transfer was based on non-medical indications. PMID- 21970790 TI - Heavy metal sorption at the muscovite (001)-fulvic acid interface. AB - The role of fulvic acid (FA) in modifying the adsorption mode and sorption capacity of divalent metal cations on the muscovite (001) surface was evaluated by measuring the uptake of Cu(2+), Zn(2+), and Pb(2+) from 0.01 m solutions at pH 3.7 with FA using in situ resonant anomalous X-ray reflectivity. The molecular scale distributions of these cations combined with those previously observed for Hg(2+), Sr(2+), and Ba(2+) indicate metal uptake patterns controlled by cation-FA binding strength and cation hydration enthalpy. For weakly hydrated cations the presence of FA increased metal uptake by approximately 60-140%. Greater uptake corresponded with increasing cation-FA affinity (Ba(2+) ~ Sr(2+) < Pb(2+) < Hg(2+)). This trend is associated with differences in the sorption mechanism: Ba(2+) and Sr(2+) sorbed in the outer portion of the FA film whereas Pb(2+) and Hg(2+) complexed with FA effectively throughout the film. The more strongly hydrated Cu(2+) and Zn(2+) adsorbed as two distinct outer-sphere complexes on the muscovite surface, with minimal change from their distribution without FA, indicating that their strong hydration impedes additional binding to the FA film despite their relatively strong affinity for FA. PMID- 21970791 TI - Serum lipid profiles are associated with disability and MRI outcomes in multiple sclerosis. AB - BACKGROUND: The breakdown of the blood-brain-barrier vascular endothelium is critical for entry of immune cells into the MS brain. Vascular co-morbidities are associated with increased risk of progression. Dyslipidemia, elevated LDL and reduced HDL may increase progression by activating inflammatory processes at the vascular endothelium. OBJECTIVE: To assess the associations of serum lipid profile variables (triglycerides, high and low density lipoproteins (HDL, LDL) and total cholesterol) with disability and MRI measures in multiple sclerosis (MS). METHODS: This study included 492 MS patients (age: 47.1 +/- 10.8 years; disease duration: 12.8 +/- 10.1 years) with baseline and follow-up Expanded Disability Status Score (EDSS) assessments after a mean period of 2.2 +/- 1.0 years. The associations of baseline lipid profile variables with disability changes were assessed. Quantitative MRI findings at baseline were available for 210 patients. RESULTS: EDSS worsening was associated with higher baseline LDL (p = 0.006) and total cholesterol (p = 0.001, 0.008) levels, with trends for higher triglyceride (p = 0.025); HDL was not associated. A similar pattern was found for MSSS worsening. Higher HDL levels (p < 0.001) were associated with lower contrast enhancing lesion volume. Higher total cholesterol was associated with a trend for lower brain parenchymal fraction (p = 0.033). CONCLUSIONS: Serum lipid profile has modest effects on disease progression in MS. Worsening disability is associated with higher levels of LDL, total cholesterol and triglycerides. Higher HDL is associated with lower levels of acute inflammatory activity. PMID- 21970802 TI - Effects of imidazoline I2 receptor ligands on morphine- and tramadol-induced antinociception in rats. AB - Currently available analgesics cannot meet the increasing clinical needs and new analgesics with better therapeutic profiles are in great demand. The imidazoline I2 receptor is an emerging drug target for analgesics. However, few studies have examined the effects of selective I2 receptor ligands on the antinociceptive activity of opioids. This study examined the antinociceptive effects of the opioids morphine (0.1-10 mg/kg) and tramadol (3.2-56 mg/kg), the nonselective I2 receptor ligand agmatine (10-100 mg/kg), and the selective I2 receptor ligands 2 (2-benzofuranyl)-2-imidazoline hydrochloride (2-BFI; 1-10 mg/kg) and 2-(4, 5 dihydroimidazol-2-yl) quinoline hydrochloride (BU224; 1-10mg/kg), alone and in combination, in a warm water tail withdrawal procedure in rats. Morphine and tramadol but not agmatine, 2-BFI or BU224 increased tail withdrawal latency in a dose-related manner at 48 degrees C water. Agmatine and 2-BFI but not BU224 dose dependently enhanced the antinociceptive effects of morphine and tramadol, shifting the dose-effect curves of morphine and tramadol leftward. The enhancement of agmatine and 2-BFI on morphine and tramadol antinociception was prevented by BU224. These results, combined with the fact that BU224 and 2-BFI share similar behavioral effects under other conditions, suggest that BU224 has lower efficacy than 2-BFI at I2 receptors, and that the enhancement of opioid antinociception by I2 receptor ligands depends on their efficacies. PMID- 21970803 TI - Preventive and therapeutic effects of caffeic acid against inflammatory injury in striatum of MPTP-treated mice. AB - Preventive or therapeutic effects of caffeic acid in brain of 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) treated mice against inflammatory injury were examined. Caffeic acid at 0.5, 1 or 2% was supplied either pre-intake or post intake for 4 weeks. Brain caffeic acid content was increased by caffeic acid pre intake at 1 and 2%, and post-intake at 2% (P < 0.05). MPTP treatment enhanced the release of interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, IL-4 and IL-10 (P < 0.05). Pre-intake of caffeic acid decreased the production of test cytokines (P < 0.05); however, post-intake only at 2% reduced the level of IL 1beta, IL-6 and TNF-alpha (P < 0.05). MPTP treatment up-regulated mRNA expression of inducible nitric oxide synthase (iNOS), neuronal NOS, cyclooxygenase (COX)-2, glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1, and increased production of nitric oxide (NO) and prostaglandin E2 (PGE2) (P < 0.05). Caffeic acid pre-intake at test doses and post-intake at 2% declined the expression of iNOS, COX-2 and GFAP; and lowered the production of NO and PGE2 (P < 0.05). MPTP treatment suppressed mRNA expression of brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor and tyrosine hydroxylase (TH), and lowered dopamine level (P < 0.05). Caffeic acid pre-intake retained the expression of these factors, maintained TH activity and protein production, and dopamine synthesis (P < 0.05). These results suggest that caffeic acid is a potent neuroprotective agent against the development of Parkinson's disease. PMID- 21970804 TI - Inhibition of stearoyl-CoA desaturase1 activates AMPK and exhibits beneficial lipid metabolic effects in vitro. AB - Stearoyl-CoA desaturase1 (SCD1) whole body deficiency protects mice from diet induced obesity. However the specific mechanism of how SCD1 deficiency protects mice from obesity is not clear yet. To understand the tissue-specific role of SCD1 in energy homeostasis, we investigated the responses of adipocytes, hepatocytes and myotubes to SCD1 inhibition. 3T3-L1 adipocytes treated with a SCD1 inhibitor had decreased expression of lipogenic genes including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and sterol-regulatory element binding protein 1c (SREBP1c) while the expression of fatty acid oxidative genes including carnitine palmitoyltransferase 1 (CPT1), uncoupling protein 2 (UCP2), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1 alpha) remained unaltered. In mouse primary hepatocytes, treatment with the inhibitor reduced the expression of FAS, ACC, and SREBP1c but increased the expression of fatty acid oxidative genes including acyl-CoA oxidase (AOX), CPT1, and PGC1-alpha. In addition, inhibitor-treated C2C12 myotubes showed decrease in ACC and FAS expression and increase in expression of CPT1, AOX and PGC1-alpha. AMP-activated protein kinase (AMPK) is known to regulate cellular metabolism in response to available energy and AMPK activation is associated with enhancement of fatty acid oxidation and suppression of lipogenesis. In all tested cell models, AMPK phosphorylation was increased significantly when SCD1 was inhibited. Taken together, our results indicate that inhibition of SCD1 activity has beneficial lipid metabolic effects of decreased lipogenesis and/or increased fatty acid oxidation, which is at least in part due to an increase of AMPK activation. PMID- 21970805 TI - The in vitro metabolism of sphingosine-1-phosphate: identification; inhibition and pharmacological implications. AB - A time-dependent decrease in S1P potency was observed in a [(35)S]-GTPgammaS binding assay using CHO-cell membranes expressing the human S1P(2) receptor. After a three hour incubation with membranes the pEC(50) of S1P was 7.09 +/- 0.03, compared to 8.59 +/- 0.10 for that obtained without pre-incubation. To determine if S1P was subjected to metabolic breakdown we developed a bioassay to measure S1P activity which confirmed the findings from the [(35)S]-GTPgammaS binding experiments. LC-MS/MS techniques were also used to measure the concentrations of S1P and its breakdown product sphingosine. In the presence of CHO-cell membranes the t(1/2) of S1P breakdown to sphingosine was 42.99 +/- 0.40 min, this is in contrast to that obtained without the inclusion of membranes (256.30 +/- 113.84 min), confirming the metabolism of S1P in vitro. Finally, the effects of different phosphatase inhibitors were investigated to determine whether it was possible to prevent the metabolism of S1P. In the presence of sodium orthovanadate, the pEC(50) for S1P obtained in the [(35)S]-GTPgammaS binding assay, after three hour pre-incubation with membranes was 8.91 +/- 0.03. In contrast that obtained without Na(3)VO(4) was 7.19 +/- 0.04. These data suggest that phosphatases are active in cell membrane preparations and are responsible for S1P metabolism in vitro. In the absence of sodium orthovanadate, it is envisaged that experiments involving exogenously applied S1P to broken cell preparations, whole cells or tissues, coupled with long incubation times will be subjected to metabolism. PMID- 21970806 TI - Chemopreventive potential of apigenin in 7,12-dimethylbenz(a)anthracene induced experimental oral carcinogenesis. AB - Aim was to investigate the chemopreventive potential of apigenin by analyzing the tumor incidence as well as monitoring lipid peroxidation, antioxidants and phase I and phase II detoxification as biomarkers during DMBA induced hamster buccal pouch carcinogenesis. Oral tumors were developed in the buccal pouches of golden Syrian hamsters using topical application of 0.5% DMBA (DMBA) three times a week for 14weeks. Tumor incidence, tumor volume and burden were measured in hamsters treated with 7,12-dimethylbenz(a)anthracene and DMBA+apigenin (2.5mg/kg body weight) treated hamsters. Oral administration of apigenin not only completely prevented the formation of oral tumors, it also brought back the status of lipid peroxidation, antioxidants and phase I and phase II detoxification agents to near normal range during DMBA induced oral carcinogenesis. The present study thus concludes that apigenin might have inhibited oral carcinogenesis by improving the status of antioxidant defense mechanism and modulated the activities of phase I and phase II detoxification cascade toward increased excretion of active metabolite of DMBA, during DMBA induced hamster buccal pouch carcinogenesis. PMID- 21970807 TI - Anti-inflammatory effects of maslinic acid, a natural triterpene, in cultured cortical astrocytes via suppression of nuclear factor-kappa B. AB - Maslinic acid (2-alpha, 3-beta-dihydroxyolean-12-en-28-oic acid) is a natural triterpenoid compound from Olea europaea. This compound prevents oxidative stress and pro-inflammatory cytokine generation in vitro. This study was planned to investigate the anti-inflammatory effects of maslinic acid in central nervous system by using rat astrocyte cultures stimulated with lipopolysaccharide (LPS). We evaluated different proteins implicated in the nuclear factor kappa B (NF kappaB) signal transducer pathway employing Western blot and quantitative real time PCR techniques. Results demonstrated that maslinic acid treatment exerted potent anti-inflammatory action by inhibiting the production of Nitric Oxide and tumor necrosis factor alpha (TNF-alpha). Western blot analysis showed that maslinic acid treatment attenuated LPS-induced translocation of NF-kappaB p65 subunit to the nucleus and prevented LPS-induced IkappaBalpha phosphorylation in a concentration-dependent manner, Moreover, maslinic acid significantly suppressed the expression of cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) at protein and mRNA levels. These results suggest that maslinic acid can potentially reduce neuroinflammation by inhibiting NF-kappaB signal transducer pathway in cultured cortical astrocytes. PMID- 21970808 TI - The kappa opioid receptor agonist SA14867 has antinociceptive and weak sedative effects in models of acute and chronic pain. AB - We examined the analgesic effect of the selective kappa opioid receptor agonist SA14867 and the balance of its antinociceptive and sedative effects. The ED(50) values of SA14867 after oral administration for acetic acid-induced writhing, first and second phases of the formalin test, and rotarod test in mice were 6.1, 9.3, 2.7, and 19.5mg/kg, respectively. These values were smaller than those of the conventional kappa receptor agonists asimadoline and U-50488H. However, the balance of the antinociceptive and sedative effects of SA14867 was better than those of the other two drugs. Orally administered SA14867 (0.1-1mg/kg) significantly improved the decreased pain threshold in a specific alternation of rhythm in an environmental temperature (SART)-stressed model by prophylactic and therapeutic treatment. Improvement in the decreased pain threshold of SA14867 treated animals was attenuated by the opioid receptor antagonist naloxone. Furthermore, orally administered asimadoline (10-100mg/kg) improved the decreased pain threshold in a SART-stressed model, but the doses were close to those known to induce sedative effects. In addition, SA14867 (0.1-1mg/kg) significantly inhibited the arthritis-induced decrease in the pain threshold. Subcutaneously administered morphine (0.1-1mg/kg) improved the decreased pain threshold in a SART-stressed model; on the contrary, morphine did not inhibit the arthritis induced decrease in the pain threshold. Moreover, orally administered SA14867 (0.1-1mg/kg) strongly attenuated mechanical allodynia and thermal hyperalgesia in a sciatic nerve ligation model. These results suggest that SA14867 has analgesic effects on chronic pain and may serve as a new therapeutic agent for pain treatment. PMID- 21970809 TI - A challenging case of gastric outlet obstruction (Bouveret's syndrome): a case report. AB - INTRODUCTION: Bouveret's syndrome is a clinically distinct form of gallstone ileus caused by the formation of a fistula between the biliary tract and duodenum. This case reinforces the need for early recognition and treatment of Bouveret's syndrome, as it is associated with high morbidity and mortality rates. CASE PRESENTATION: An 82-year-old Caucasian woman presented with signs and symptoms of small bowel obstruction. Her laboratory workup showed elevated alkaline phosphatase and amylase levels. Computed tomography of her abdomen revealed pneumobilia, a choledochoduodenal fistula and a gallstone obstructing her distal duodenum. The impacted gallstone could not be extracted endoscopically, so our patient underwent open enterolithotomy successfully. However, the postoperative course was complicated by myocardial infarction, respiratory failure and disseminated intravascular coagulation. She died 22 days after surgery, secondary to cardiopulmonary arrest. CONCLUSION: This case clearly highlights the considerable morbidity and mortality associated with Bouveret's syndrome. PMID- 21970811 TI - The epigenome as a target for heritable environmental disruptions of cellular function. AB - The environment is a well-established source of damaging or disrupting influences on cellular function. In the past, studies of the mechanisms by which such disruptions occur have focused largely on either direct toxic effects on cellular function at the protein or cell signaling level, or mutagenic effects that impact the genome. In recent years there has been a growing appreciation for the potential for environmental influences to disrupt the epigenome and mechanisms of epigenetic regulation within the cell. Indeed, because of the inherent lability of the epigenome, this represents a primary target for environmentally induced disruption. This review summarizes the manner in which the epigenome normally regulates cellular function, the effects of disruptions on this function, and the manner in which such disruptions may or may not be corrected within the organism and/or transmitted to subsequent generations. PMID- 21970810 TI - Duodenal and faecal microbiota of celiac children: molecular, phenotype and metabolome characterization. AB - BACKGROUND: Epidemiology of celiac disease (CD) is increasing. CD mainly presents in early childhood with small intestinal villous atrophy and signs of malabsorption. Compared to healthy individuals, CD patients seemed to be characterized by higher numbers of Gram-negative bacteria and lower numbers Gram positive bacteria. RESULTS: This study aimed at investigating the microbiota and metabolome of 19 celiac disease children under gluten-free diet (treated celiac disease, T-CD) and 15 non-celiac children (HC). PCR-denaturing gradient gel electrophoresis (DGGE) analyses by universal and group-specific primers were carried out in duodenal biopsies and faecal samples. Based on the number of PCR DGGE bands, the diversity of Eubacteria was the higher in duodenal biopsies of T CD than HC children. Bifidobacteria were only found in faecal samples. With a few exceptions, PCR-DGGE profiles of faecal samples for Lactobacillus and Bifidobacteria differed between T-CD and HC. As shown by culture-dependent methods, the levels of Lactobacillus, Enterococcus and Bifidobacteria were confirmed to be significantly higher (P = 0.028; P = 0.019; and P = 0.023, respectively) in fecal samples of HC than in T-CD children. On the contrary, cell counts (CFU/ml) of presumptive Bacteroides, Staphylococcus, Salmonella, Shighella and Klebsiella were significantly higher (P = 0.014) in T-CD compared to HC children. Enterococcus faecium and Lactobacillus plantarum were the species most diffusely identified. This latter species was also found in all duodenal biopsies of T-CD and HC children. Other bacterial species were identified only in T-CD or HC faecal samples. As shown by Randomly Amplified Polymorphic DNA-PCR analysis, the percentage of strains identified as lactobacilli significantly (P = 0.011) differed between T-CD (ca. 26.5%) and HC (ca. 34.6%) groups. The metabolome of T CD and HC children was studied using faecal and urine samples which were analyzed by gas-chromatography mass spectrometry-solid-phase microextraction and 1H Nuclear Magnetic Resonance. As shown by Canonical Discriminant Analysis of Principal Coordinates, the levels of volatile organic compounds and free amino acids in faecal and/or urine samples were markedly affected by CD. CONCLUSION: As shown by the parallel microbiology and metabolome approach, the gluten-free diet lasting at least two years did not completely restore the microbiota and, consequently, the metabolome of CD children. Some molecules (e.g., ethyl-acetate and octyl-acetate, some short chain fatty acids and free amino acids, and glutamine) seems to be metabolic signatures of CD. PMID- 21970812 TI - The ratio of growth differentiation factor 9: bone morphogenetic protein 15 mRNA expression is tightly co-regulated and differs between species over a wide range of ovulation rates. AB - Recent evidence suggests that the species-specific ovulation-rate phenotypes may be influenced by differences in the expression levels of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) mRNA and protein. The aim of this study was to compare GDF9 and BMP15 mRNA levels in individual denuded oocytes (DO) from a range of single (i.e. cow, red deer), single-to triple (i.e. sheep) and high (i.e. pig, mouse, rat) ovulation-rate species. Compared to all other species studied, GDF9 mRNA levels were lower in DO of cows and deer, whilst BMP15 levels were highest in DO of pigs. There was no detectable expression of either GDF9 or BMP15 mRNA in CC from any species. The ratio of GDF9:BMP15 mRNA expression was highly correlated (R(2)>0.80) within each species but differed markedly between species (P<0.01). Thus, we conclude that the ratio of GDF9:BMP15 mRNA is species-specific across a wide range of ovulation-rate phenotypes. PMID- 21970813 TI - Circadian rhythms research or "chronobiology" has come of age. PMID- 21970814 TI - A multivariate, multitaper approach to detecting and estimating harmonic response in cortical optical imaging data. AB - The efficiency and accuracy of cortical maps from optical imaging experiments have been improved using periodic stimulation protocols. The resulting data analysis requires the detection and estimation of periodic information in a multivariate dataset. To date, these analyses have relied on discrete Fourier transform (DFT) sinusoid estimates. Multitaper methods have become common statistical tools in the analysis of univariate time series that can give improved estimates. Here, we extend univariate multitaper harmonic analysis methods to the multivariate, imaging context. Given the hypothesis that a coherent oscillation across many pixels exists within a specified bandwidth, we investigate the problem of its detection and estimation in noisy data by constructing Hotelling's generalized T(2)-test. We then extend the investigation of this problem in two contexts, that of standard canonical variate analysis (CVA) and that of generalized indicator function analysis (GIFA) which is often more robust in extracting a signal in spatially correlated noise. We provide detailed information on the fidelities of the mean estimates found with our methods and comparison with DFT estimates. Our results indicate that GIFA provides particularly good estimates of harmonic signals in spatially correlated noise and is useful for detecting small amplitude harmonic signals in applications such as biological imaging measurements where spatially correlated noise is common. We demonstrate the power of our methods with an optical imaging dataset of the periodic response to a periodically rotating oriented drifting grating stimulus experiment in cat visual cortex. PMID- 21970815 TI - Density functional study of the electric double layer formed by a high density electrolyte. AB - We use a classical density functional theory (DFT) to study the electric double layer formed by charged hard spheres near a planar charged surface. The DFT predictions are found to be in good agreement with recent computer simulation results. We study the capacitance of the charged hard-sphere system at a range of densities and surface charges and find that the capacitance exhibits a local minimum at low ionic densities and small electrode charge. Although this charging behavior is typical for an aqueous electrolyte solution, the local minimum gradually turns into a maximum as the density of the hard spheres increases. Charged hard spheres at high density provide a reasonable first approximation for ionic liquids. In agreement with experiment, the capacitance of this model ionic liquid double layer has a maximum at small electrode charge density. PMID- 21970816 TI - Level of muscle regeneration in limb-girdle muscular dystrophy type 2I relates to genotype and clinical severity. AB - BACKGROUND: The balance between muscle regeneration and ongoing degeneration is a relationship that greatly influences the progression of muscular dystrophy. Numerous factors may influence the muscle regeneration, but more information about the relationship between genotype, clinical severity and the ability to regenerate is needed. METHODS: Muscle biopsies were obtained from the tibialis anterior muscle, and frozen sections were stained for general histopathological and immunohistological evaluation. Differences between groups were considered statistical significant at P < 0.05 using Student's unpaired t-test. RESULTS: We found that all patients with limb-girdle muscular dystrophy type 2I (LGMD2I) had a large number of internally nucleated fibers, a sign of previous regeneration. The level of expression of muscle-specific developmental proteins, such as neonatal myosin heavy chain (nMHC) and myogenin, was related to the clinical severity. Additionally, we found that the majority of nMHC-positive fibers did not stain positively for utrophin in patients who were compound heterozygous for the L276I mutation, suggesting that the predominant form of regeneration in these patients is fiber repair rather than formation of new fibers. Double staining showed that many smaller nMHC-positive fibers were positive for antibodies against the glycosylation on alpha-dystroglycan, suggesting that such glycosylation may be a result of muscle regeneration. CONCLUSION: Severely affected patients with LGMD2I have a high level of muscle degeneration, which leads to a high rate of regeneration, but this is insufficient to change the imbalance between degeneration and regeneration, ultimately leading to progressive muscle wasting. Detailed information regarding the level and rate of muscle regeneration and potential obstructions of the regenerative pathway should be of use for future therapies involving satellite-cell activation. PMID- 21970818 TI - Development of a stable dual functional coating with low non-specific protein adsorption and high sensitivity for new superparamagnetic nanospheres. AB - To overcome major challenges of non-specific protein adsorption on nanoparticles for nanosensing and nanodiagnosis, an efficient method for robust chemical modification was developed to achieve excellent specific biorecognition and long term stability in complex biomedia. This method is demonstrated by a highly specific and sensitive immunoassay (IA), using superparamagnetic nanospheres (NSs) with high magnetite content. The non-specific protein adsorption on the NSs was suppressed dramatically when modified with dual functional poly(carboxybetaine methacrylate) (polyCBMA) via surface-initiated atom transfer radical polymerization (SI-ATRP) and chemically grafted with antibodies of the beta subunit of human chorionic gonadotrop (anti-beta-hCG). The response to hCG of IA NSs with polyCBMA coatings was highly consistent in either phosphate buffered saline (PBS) or 50% fetal bovine serum (FBS), which is far less variable than the response of the IA NSs without polyCBMA coatings. After all, a very robust platform for IA NSs with excellent specific biorecognition was obtained. It is expected that this method for nanoparticle modification could be widely used in ultrasensitive nanosensing and nanodiagnosis in the future. PMID- 21970817 TI - Microglial depletion using intrahippocampal injection of liposome-encapsulated clodronate in prolonged hypothermic cardiac arrest in rats. AB - Trauma patients who suffer cardiac arrest (CA) from exsanguination rarely survive. Emergency preservation and resuscitation using hypothermia was developed to buy time for resuscitative surgery and delayed resuscitation with cardiopulmonary bypass (CPB), but intact survival is limited by neuronal death associated with microglial proliferation and activation. Pharmacological modulation of microglia may improve outcome following CA. Systemic injection of liposome-encapsulated clodronate (LEC) depletes macrophages. To test the hypothesis that intrahippocampal injection of LEC would attenuate local microglial proliferation after CA in rats, we administered LEC or PBS into the right or left hippocampus, respectively. After rapid exsanguination and 6min no flow, hypothermia was induced by ice-cold (IC) or room-temperature (RT) flush. Total duration of CA was 20min. Pre-treatment (IC, RTpre) and post-treatment (RTpost) groups were studied, along with shams (cannulation only) and CPB controls. On day 7, shams and CPB groups showed neither neuronal death nor microglial activation. In contrast, the number of microglia in hippocampus in each individual group (IC, RTpre, RTpost) was decreased with LEC vs. PBS by ~34 46% (P<0.05). Microglial proliferation was attenuated in the IC vs. RT groups (P<0.05). Neuronal death did not differ between hemispheres or IC vs. RT groups. Thus, intrahippocampal injection of LEC attenuated microglial proliferation by ~40%, but did not alter neuronal death. This suggests that microglia may not play a pivotal role in mediating neuronal death in prolonged hypothermic CA. This novel strategy provides us with a tool to study the specific effects of microglia in hypothermic CA. PMID- 21970819 TI - Competitive, non-competitive, and mixed format cleavable tag immunoassays. AB - Immunoassays are one of the most useful diagnostic techniques in disease assessment, drug metabolite analysis, and environmental applications due largely in part to the selectivity and sensitivity provided by antibody-antigen interactions. Here, a multiplexed immunoassay termed cleavable tag immunoassay (CTI) was performed in competitive, non-competitive, and mixed formats for the analysis of proteins and small molecule biomarkers of inflammation and tissue damage. Microchip capillary electrophoresis (MCE) with fluorescence detection was employed for the analysis of fluorescently labeled tags corresponding to the analytes of interest cleaved from the detection antibodies. For this work we have selected 3-nitrotyrosine (3-NT) a molecule indicative of reactive nitrogen species (RNS), thyroxine (T4) a molecule used to monitor thyroid gland function, and C-reactive protein (CRP) a marker of chronic inflammation as model analytes to demonstrate the assay principles. The simultaneous detection of 3 nitrotyrosine (3-NT) and thyroxine (T4) was carried out as a proof-of-principle for the competitive CTI while non-competitive CTI performance was demonstrated via the analysis of C-reactive protein (CRP). Limit of detections (LOD) and dynamic ranges were investigated. LOD for 3-NT, T4, and CRP were 0.5MUg/mL, 23nM, and 5MUg/mL, respectively thus demonstrating the ability of the CTI to detect proteins and small molecules within clinical reference ranges. Moreover, this is the first report of the use of mixed format CTI chemistry for the simultaneous detection of proteins (CRP) and small molecules (3-NT) in a single assay. The success of this work demonstrates the ability of CTI to analyze intact proteins and small molecule biomarkers simultaneously. PMID- 21970821 TI - Vacancies in CuInSe2: new insights from hybrid-functional calculations. AB - We calculate the energetics of vacancies in CuInSe(2) using a hybrid functional (HSE06, HSE standing for Heyd, Scuseria and Ernzerhof), which gives a better description of the band gap compared to (semi)local exchange-correlation functionals. We show that, contrary to present beliefs, copper and indium vacancies induce no defect levels within the band gap and therefore cannot account for any experimentally observed levels. The selenium vacancy is responsible for only one level, namely, a deep acceptor level epsilon(0/2-). We find strong preference for V(Cu) and V(Se) over V(In) under practically all chemical conditions. PMID- 21970820 TI - 4th Annual Symposium on Self Monitoring of Blood Glucose (SMBG) Applications and Beyond, May 12-14, 2011, Budapest, Hungary. PMID- 21970822 TI - Post-menopausal women with rheumatoid arthritis who are treated with raloxifene or alendronate or glucocorticoids have lower serum undercarboxylated osteocalcin levels. AB - BACKGROUND: Serum undercarboxylated osteocalcin (ucOC) is a biochemical bone marker of vitamin K insufficiency. It had been reported that bone resorption inhibitors tend to decrease the serum ucOC level in patients with primary osteoporosis. In rheumatoid arthritis (RA) patients, these results have never been reported. AIM: We investigated risk factors which could change serum ucOC level in post-menopausal women with RA (no.=100). SUBJECTS AND METHODS: Twenty patients received no bone resorption inhibitor (control), 30 received raloxifene (RLX), while 50 received alendronate (ALN). This cross-sectional study was limited to patients with low RA disease activity (Disease Activity Score-28 <=3.2). We measured serum ucOC, and the data were analyzed by multivariable analysis, including ucOC and the other variables. RESULTS: Scheffe's F test demonstrated a significant difference in serum ucOC levels between controls and the RLX group (p<0.01), and between controls and the ALN group (p<0.01). Serum ucOC levels were low in both treated groups. An adjusted multivariate analysis was performed for the variables: bone resorption inhibitor use, serum alkaline phosphatase, glucocorticoid dose, age, estimated glomerular filtration rate and matrix metalloproteinase 3. As a result, serum ucOC inversely correlated with bone resorption inhibitor use (p<0.01) and oral glucocorticoid dose (p<0.01), which were independent risk factors of lowering ucOC. CONCLUSIONS: Bone resorption inhibitors and glucocorticoids were independent risk factors for lowering serum ucOC levels in post-menopausal RA patients. PMID- 21970823 TI - Lipopolysaccharide modulates astrocytic S100B secretion: a study in cerebrospinal fluid and astrocyte cultures from rats. AB - BACKGROUND: Inflammatory responses in brain are primarily mediated by microglia, but growing evidence suggests a crucial importance of astrocytes. S100B, a calcium-binding protein secreted by astrocytes, has properties of a neurotrophic or an inflammatory cytokine. However, it is not known whether primary signals occurring during induction of an inflammatory response (e.g. lipopolysaccharide, LPS) directly modulate S100B. METHODS: In this work, we evaluated whether S100B levels in cerebrospinal fluid (CSF) and serum of Wistar rats are affected by LPS administered by intraperitoneal (IP) or intracerebroventricular (ICV) injection, as well as whether primary astrocyte cultures respond directly to lipopolysaccharide. RESULTS: Our data suggest that S100B secretion in brain tissue is stimulated rapidly and persistently (for at least 24 h) by ICV LPS administration. This increase in CSF S100B was transient when LPS was IP administered. In contrast to these S100B results, we observed an increase in in TNFalpha levels in serum, but not in CSF, after IP administration of LPS. In isolated astrocytes and in acute hippocampal slices, we observed a direct stimulation of S100B secretion by LPS at a concentration of 10 MUg/mL. An involvement of TLR4 was confirmed by use of specific inhibitors. However, lower levels of LPS in astrocyte cultures were able to induce a decrease in S100B secretion after 24 h, without significant change in intracellular content of S100B. In addition, after 24 h exposure to LPS, we observed a decrease in astrocytic glutathione and an increase in astrocytic glial fibrillary acidic protein. CONCLUSIONS: Together, these data contribute to the understanding of the effects of LPS on astrocytes, particularly on S100B secretion, and help us to interpret cerebrospinal fluid and serum changes for this protein in neuroinflammatory diseases. Moreover, non-brain S100B-expressing tissues may be differentially regulated, since LPS administration did not lead to increased serum levels of S100B. PMID- 21970824 TI - Diffuse large B-cell non Hodgkin's lymphoma in a 65-year-old woman presenting with hypopituitarism and recovering after chemotherapy: a case report. AB - INTRODUCTION: Diffuse large B-cell non Hodgkin's lymphoma may involve the pituitary either as a primary central nervous system lymphoma or, more frequently, as metastasis from systemic lymphoma leading to hypopituitarism. A partial recovery of pituitary function after treatment with chemotherapy has previously been described but complete recovery with cessation of all hormone supplements is excessively rare. We report a patient presenting with anterior hypopituitarism with subsequent complete and sustained recovery of pituitary function after successful treatment of the lymphoma. CASE PRESENTATION: A 65-year old Caucasian woman with lethargy, loss of appetite and peripheral edema was found to have anterior hypopituitarism. Magnetic resonance imaging showed no mass lesions in the pituitary although a positron emission tomography scan showed abnormal pituitary activity. An abdominal computed tomography scan revealed multiple intra-abdominal lymph nodes, which on histology proved diagnostic of diffuse large B-cell non Hodgkin's lymphoma. She received six cycles of R-CHOP chemotherapy, after which she achieved a complete metabolic response at all known previous sites of the disease, confirmed by positron emission tomography scanning. Concomitant with the tumor response, there was full recovery of adrenal, thyroid and gonadal axes which has persisted at 10 months follow-up. CONCLUSION: Although rare, it is important to recognize lymphomatous infiltration of the pituitary as a potentially reversible cause of hypopituitarism. PMID- 21970825 TI - Acute inflammatory aortitis: utility of hybrid imaging with positron emission tomography/computed tomography in diagnosis and follow-up. PMID- 21970826 TI - Hyperimmunoglobulin E syndromes in pediatrics. AB - PURPOSE OF REVIEW: The hyper-IgE syndromes (HIES) are primary immunodeficiencies characterized by eczema, sinopulmonary infections, and elevated serum IgE. This review discusses the clinical similarities and differences between the autosomal dominant HIES (AD-HIES) and autosomal recessive HIES (AR-HIES) forms, as well as their causative genetic and pathophysiological mechanisms. RECENT FINDINGS: Over the past 4 years, three genetic defects have been identified in HIES. Mutations in STAT3 are associated with AD-HIES, whereas mutations in DOCK8, or rarely TYK2, are associated with AR-HIES. Recent work has confirmed that measuring T helper 17 cell numbers can help predict STAT3 mutations. In AR-HIES, loss of DOCK8 expression was found to impair T cell expansion and durable-specific antibody production by B cells. These factors probably contribute to the viral skin and other infectious susceptibilities, severe allergies, and high risk of malignancies that define this disorder. SUMMARY: Establishing the molecular diagnosis of HIES is important for optimal patient management. Infections in AD HIES are usually well controlled by antibiotics. By contrast, the viral infections in AR-HIES are difficult to manage. Their higher mortality and progressive course emphasizes the need to identify AR-HIES patients early, for consideration of potentially curative hematopoietic cell transplantation. PMID- 21970827 TI - Translational research: Rett syndrome and tuberous sclerosis complex. AB - PURPOSE OF REVIEW: Rare genetic diseases that affect behavior and cognition provide a unique opportunity to study the mechanisms of neurodevelopmental disorders through the examination of animal models, which can lead to development of hypotheses and treatments testable in human beings. Rett syndrome (RTT) and tuberous sclerosis complex (TSC) are both Mendelian disorders that present with autism, epilepsy, and intellectual disability, in which animal model work has been directly translated into clinical treatment trials currently underway. Here, we review the recent advances in our understanding of RTT and TSC pathogenesis and signaling pathways that may be targeted for novel treatments. RECENT FINDINGS: Animal models generated by engineering mutant forms of the mouse homologs of human genes involved in RTT and TSC have allowed dissection of the molecular pathology. They have further acted as in-vivo assays of potential therapeutic strategies that have translated to human clinical trials. SUMMARY: Single-gene disorders associated with neurodevelopmental disorders provide powerful model systems to study the roles of individual molecules and associated signaling pathways in the genesis of autism, epilepsy, cognitive impairment, and neuropsychiatric symptoms. These diseases are leading to disease-modifying human therapies that may eventually translate to wider therapeutic strategies for autism. PMID- 21970829 TI - Atopic dermatitis: from new pathogenic insights toward a barrier-restoring and anti-inflammatory therapy. AB - PURPOSE OF REVIEW: Recent published work on atopic dermatitis focusing on the pathogenesis and epidemiology, which have a direct effect on treatment, is presented. RECENT FINDINGS: Worldwide, the incidence of atopic dermatitis is still increasing, although a plateau seems to be reached in certain industrialized countries. In addition to the filaggrin missense mutations, other mechanisms responsible for impaired skin-barrier function have been identified. These findings have a direct impact on therapy as well as behavior strategies. The barrier defect and the resulting inflammation in the skin, in particular interleukin (IL)-17-mediated responses, play an important role in promoting allergic airway responses and food allergy. SUMMARY: These recent findings on epithelial barrier defects, as well as cells and cytokines important for atopic dermatitis development, provide new insights into its pathogenesis, help to characterize patient subgroups, and identify new therapeutic strategies. PMID- 21970828 TI - Common neurological co-morbidities in autism spectrum disorders. AB - PURPOSE OF REVIEW: Autism spectrum disorders (ASDs) are heterogeneous neurodevelopmental disorders associated with various co-morbidities. Neurological co-morbidities include motor impairments, epilepsy, and sleep dysfunction. These impairments have been receiving more attention recently, perhaps because of their significant impact on the behavior and cognitive function of children with ASDs. Here, we review the epidemiology, etiology, and clinical approach to these neurological co-morbidities and highlight future research directions. RECENT FINDINGS: Motor impairments include stereotypies, motor delays, and deficits, such as dyspraxia, incoordination, and gait problems. Sleep dysfunction typically presents as difficulty with sleep onset and prolonged awakenings during the night. Recent data suggest that abnormalities in melatonin may affect sleep and may be a potential treatment target. There is no classic epilepsy syndrome associated with ASDs. Intellectual disability, syndromic autism, and female sex are specific risk factors. Recent research has focused on identifying the overlapping pathways between these neurological co-morbidities and the core deficits in ASDs, which may have direct and powerful implications for treatment and prognosis. SUMMARY: Motor impairment, epilepsy, and sleep dysfunction are common neurological co-morbidities in ASDs. Clinicians should be aware that recognition and treatment of these issues may improve the function and outcome of children with ASDs. PMID- 21970831 TI - Recent advances in autism spectrum disorders. PMID- 21970830 TI - Recent advances in understanding the neural bases of autism spectrum disorder. AB - PURPOSE OF REVIEW: This article reviews current work investigating the neural bases of autism spectrum disorder (ASD) within the discipline of electrophysiological brain research. The manuscript focuses primarily on advances in understanding related to social information processing and interconnectivity among brain systems in ASD. RECENT FINDINGS: Recent research indicates anomalous function of social brain regions in ASD and highlights the specificity of processing problems to these systems. Atypical activity in this circuitry may reflect genetic susceptibility for ASD, with increased activity in compensatory areas marking the distinction between developing and not developing the disorder. Advances in understanding connectivity in ASD are highlighted by novel work providing initial evidence of atypical interconnectivity in infancy. SUMMARY: Emerging understanding of neural dysfunction in ASD indicates consistent but heterogeneous dysfunction across brain systems in ASD. Key objectives for the immediate future include the use of multimethod approaches that encompass temporal and spatial imaging; behavioral phenotyping carried out in developmental context to reveal subgroups defined uniquely by trajectories; and individual specific profiles of behavioral performance and brain function. PMID- 21970832 TI - Gene therapy for primary immunodeficiency. AB - PURPOSE OF REVIEW: Haematopoietic stem cell transplantation (HSCT) is the mainstay of definitive treatment for children with a wide spectrum of primary immunodeficiencies (PIDs), but outcome is heavily dependent on the availability of a human leukocyte antigen-matched donor. Gene therapy using autologous gene corrected haematopoietic stem cells is an alternative for patients who lack an appropriate donor and has been used to treat children and adults with specific forms of PID, such as severe combined immunodeficiency, for over 10 years. This review summarizes the encouraging long-term outcome data available from these clinical trials and considers the important adverse events that have arisen. Current strategies directed towards improving the efficacy and safety profile of gene therapy will be discussed. RECENT FINDINGS: Effective clinical trials have been conducted for other forms of PID including chronic granulomatous disease and Wiskott-Aldrich syndrome. Preclinical and clinical studies are now focussed on the development of improved viral vectors giving more regulated or tissue specific transgene expression with reduced mutagenic potential. SUMMARY: Gene therapy offers a valuable alternative management option for selected immunodeficiency patients who lack a suitable donor for HSCT. Clinical trials have confirmed proof-of-principle in terms of stem cell transduction and subsequent immune reconstitution, but have also highlighted the potential for clonal disturbances related to semi-random vector insertion within the genome. PMID- 21970833 TI - Congenital disorders of glycosylation: sweet news. AB - PURPOSE OF REVIEW: Congenital disorders of glycosylation (CDG) have grown enormously since the discovery of the first protein glycosylation defect in 1980, presenting with a broad clinical spectrum. Expansion in number and complexity of the CDG group has even necessitated a new nomenclature. By 2011, the CDG group includes lipid glycosylation disorders and other related processes and almost 50 distinct disorders. RECENT FINDINGS: Current research has not only expanded the spectrum of CDG types, but has also given novel insight into those previously described. The discovery of genetic defects in the conserved oligomeric Golgi complex, affecting protein glycosylation and processing through the secretory pathway, raised the concept of 'secondary' glycosylation disorders. The number of lipid glycosylation disorders, linking lipid synthesis to CDG, that were previously regarded as rare, is also increasing rapidly. In other areas of research, the bridge between muscular dystrophies and metabolic disorders is being further reinforced with the discovery of additional defects in the DPM-CDG subgroup, a CDG characterized by significant muscle involvement. SUMMARY: It is of great importance that clinicians stay up-to-date on the field of CDG and consider it in their differential diagnosis of unknown syndromal presentations. Nevertheless, many advances have yet to be made, including information on the natural course of CDG. The lack of treatment for nearly all CDG types is striking, and the field must continue to push for innovative therapies. Clinicians and researchers must work together to describe the natural course and, most importantly, collaborate to find new therapies. PMID- 21970835 TI - Specificity and sensitivity of 99mTc-EDDA/HYNIC-Tyr3-octreotide (99mTc-TOC) for imaging neuroendocrine tumors. AB - OBJECTIVES: Gastroenteropancreatic neuroendocrine tumors (NETs) are cancers originating from neuroendocrine organs such as the pancreas, pituitary, thyroid, and adrenal glands and tumors arising from the diffuse neuroendocrine cells that are widely distributed throughout the body. NETs express somatostatin (SS) and contain a high density of SS receptors; therefore, they can be specifically targeted with SS-based radiopharmaceuticals. The aim of this research was to determine the validity in terms of specificity, sensitivity, and the agreement beyond chance with the biopsy (gold standard) of the 99mTc-EDDA-HYNIC Tyr3octreotide (99mTc-TOC) to image and localize NETs and their metastases. MATERIALS AND METHODS: Freeze-dried kits containing 0.0125 mg HYNIC-octreotide and co-ligands were easily labeled and quality controlled within the hospital radiopharmacy. Fifty-six consecutive Mexican patients with a previous presumptive diagnosis of NETs underwent several clinical and laboratory studies and were referred to the Nuclear Medicine Department for a routine scan with 99mTc-TOC. The patients were injected with 500-600 MBq 99mTc-TOC, and whole-body images were obtained 2 h later with a SPECT or a SPECT/CT camera. Two nuclear medicine physicians observed the images and classified them as 17 negative and 39 positive. After correlating the image of each patient with our 'gold standard' (biopsy, clinical history, morphological images, and tumor marker assays), the 99mTc-TOC images were classified by the same two physicians as 12 true negatives, five false negatives, 38 true positives and one false positive. RESULTS: The validity of 99mTc-TOC in terms of relative frequencies with corresponding 95% confidence intervals were as follows: 92.3% (64-100%) specificity; 88.4% (78-97%) sensitivity; and the agreement beyond chance was 73% (60-84%). The positive predictive value was 97.4% (87-100%); the negative predicted value was 70.6% (48 93%); the accuracy was 89.3% (89-97%); and the prevalence was 76.8% (64-87%). CONCLUSION: Because of these high values, we strongly recommend scintigraphy with the Mexican-produced 99mTc-TOC for the localization of NETs and their metastases, and we conclude that it is a good tool for detecting neuroendocrine disease in a Mexican population. PMID- 21970834 TI - Diffuse increased splenic F-18 fluorodeoxyglucose uptake may be an indirect sign of acute pyogenic cause rather than tuberculous in patients with infectious spondylitis. AB - OBJECTIVE: The aim of this study was to investigate whether diffuse increased splenic fluorodeoxyglucose (FDG) uptake may be an indirect sign of an acute pyogenic cause of infectious spondylitis (IS). METHODS: A retrospective review identified consecutive records of patients with IS who underwent F-18 FDG positron emission tomography-computed tomography scans between January 2007 and July 2008 and recruited 23 patients (57.8 +/- 15.6 years, range: 20-81 years, eight men, 15 women) and their hematological laboratory data. The regions of interest were used to measure the maximum standardized uptake value (SUVmax) for the bone marrow (BM), liver, and spleen in each patient. We calculated the spleen/liver ratio (S/L ratio) by dividing the spleen SUVmax by liver SUVmax and the spleen/BM ratio (S/B ratio) by dividing spleen SUVmax by BM SUVmax as a parameter to assess the splenic FDG uptake. RESULTS: The acute pyogenic cause of the IS group showed statistically significantly higher values of spleen SUVmax (median, 1.71 vs. 1.16, P=0.0108), S/L ratio (median, 1.08 vs. 0.88, P=0.0454), and S/B ratio (median, 1.30 vs. 0.94, P=0.0055) than the chronic tuberculous cause of the IS. The optimal cut-off values for the quantitative indices were spleen SUVmax>1.49, S/B ratio>0.957, and S/L ratio>0.889. CONCLUSION: On the basis of the results presented, this study demonstrated that some quantitative indices from F-18 FDG positron emission tomography/computed tomography images could be indirect signs of an acute pyogenic cause of the IS. Among the various quantitative indices, spleen SUVmax, S/B ratio, and S/L ratio were potent indicators for an acute pyogenic cause of the IS. PMID- 21970836 TI - Striving to be prepared for the painful: Management strategies following a family member's diagnosis of advanced cancer. AB - BACKGROUND: Cancer has consequences not only for the sick person but also for those who have a close relationship with that person. Greater knowledge about how family members manage the situation in the period immediately following the diagnosis means greater opportunity to provide the best possible support for the family. The purpose of this study was to explore management strategies that family members use when the patient is in the early stage of treatment for advanced cancer. METHODS: Twenty family members of cancer patients were included in the study shortly after the diagnosis. The patients had been diagnosed 8-14 weeks earlier with advanced lung cancer or gastrointestinal cancer. The data were collected in interviews with family members and subjected to qualitative latent content analysis. Through the identification of similarities and dissimilarities in the units of meaning, abstraction into codes and sub-themes became possible. The sub-themes were then brought together in one overarching theme. RESULTS: The overall function of management strategies is expressed in the theme Striving to be prepared for the painful. The family members prepare themselves mentally for the anticipated tragedy. Family relationships become increasingly important, and family members want to spend all their time together. They try to banish thoughts of the impending death and want to live as normal a life as possible. It becomes important to family members to live in the present and save their energy for the time when they will need it the most. How participants handle their worries, anxiety and sadness can be categorized into seven sub-themes or management strategies: Making things easier in everyday life, Banishing thoughts about the approaching loss, Living in the present, Adjusting to the sick person's situation, Distracting oneself by being with others, Shielding the family from grief, and Attempting to maintain hope. CONCLUSIONS: The findings revealed that the family members have their own resources for handling the early stage of the cancer trajectory in an acceptable way. There is a need for longitudinal studies to generate knowledge for designing evidence-based intervention programmes that can prevent future ill-health in these vulnerable family members. PMID- 21970837 TI - The inhibition of lipoprotein-associated phospholipase A2 exerts beneficial effects against atherosclerosis in LDLR-deficient mice. AB - AIM: To investigate the effects of darapladib, a specific inhibitor of lipoprotein-associated phospholipase A2 (lp-PLA2), on inflammation and atherosclerotic formation in the low density lipoprotein receptor (LDLR) deficient mice. METHODS: Six-week-old LDLR-deficient mice were fed an atherogenic high-fat diet for 17 weeks and then randomly divided into two groups. One group was administered darapladib (50 mg.kg(-1).d(-1); po) for 6 weeks. The other group was administered saline as a control. Serum lipid levels were measured using the corresponding kits, and three inflammatory markers--interleukin-6 (IL-6), C reactive protein (hs-CRP), and platelet activating factor (PAF)--were determined using ELISA. Atherosclerotic plaque areas were stained with Sudan IV, and inflammatory gene expression at the lesions was evaluated using quantitative real time PCR. RESULTS: The body weight and serum lipid level between the two groups were similar at the end of the dietary period. The serum lp-PLA2 activity, hs-CRP and IL-6 levels, however, were significantly reduced in the darpladib group. The inhibition of lp-PLA2 did not alter the serum PAF level. Furthermore, the plaque area, from the aortic arch to the abdominal aorta, was significantly reduced in the darpladib group. Additionally, the expression of inflammatory genes monocyte chemotactic protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) was significantly reduced at the lesions in the darapladib group. CONCLUSION: Inhibition of lp-PLA2 by darapladib decreases the inflammatory burden and atherosclerotic plaque formation in LDLR-deficient mice, which may be a new strategy for the treatment of atherosclerosis. PMID- 21970838 TI - Metabolism of novel anti-HIV agent 3-cyanomethyl-4-methyl-DCK by human liver microsomes and recombinant CYP enzymes. AB - AIM: To investigate the metabolism of 3-cyanomethyl-4-methyl-DCK (CMDCK), a novel anti-HIV agent, by human liver microsomes (HLMs) and recombinant cytochrome P450 enzymes (CYPs). METHODS: CMDCK was incubated with HLMs or a panel of recombinant cytochrome P450 enzymes including CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4, and 3A5. LC-ion trap mass spectrometry was used to separate and identify CMDCK metabolites. In the experiments with recombinant cytochrome P450 enzymes, specific chemical inhibitors combined with CYP antibodies were used to identify the CYP isoforms involved in CMDCK metabolism. RESULTS: CMDCK was rapidly and extensively metabolized by HLMs. Its intrinsic hepatic clearance estimated from the in vitro data was 19.4 mL.min(-1).kg(-1), which was comparable to the mean human hepatic blood flow rate (20.7 mL.min(-1).kg(-1)). The major metabolic pathway of CMDCK was oxidation, and a total of 14 metabolites were detected. CYP3A4 and 3A5 were found to be the principal CYP enzymes responsible for CMDCK metabolism. CONCLUSION: CMDCK was metabolized rapidly and extensively in human hepatic microsomes to form a number of oxidative metabolites. CYP3A4 and 3A5 were the predominant enzymes responsible for the oxidation of CMDCK. PMID- 21970839 TI - AIMing at metabolic syndrome. -Towards the development of novel therapies for metabolic diseases via apoptosis inhibitor of macrophage (AIM).-. AB - Metabolic syndrome (MetS) is a cascade of metabolic diseases, starting with obesity and progressing to atherosclerosis, and is often fatal because of serious cardiovascular problems such as heart/brain infarction and hemorrhage. Accumulating evidence has revealed a critical involvement of inflammatory responses triggered by lesional macrophages in the pathogenesis of MetS. Importantly, we found that macrophages are associated with disease progression, not only in the induction of inflammation but also in the production of apoptosis inhibitor of macrophages (AIM), which we initially identified as a soluble factor expressed by macrophages. In atherosclerotic plaques, AIM is highly expressed by foam macrophages and inhibits apoptosis of these cells, which results in the accumulation of macrophages, causing inflammatory responses within the lesion, and ultimately disease progression. In adipose tissue, macrophage-derived AIM is incorporated into adipocytes through CD36-mediated endocytosis, thereby reducing the activity of cytosolic fatty acid synthase. This unique response stimulates lipolysis, resulting in a decrease in adipocyte size, which is physiologically relevant to the prevention of obesity. The lipolytic response also stimulates inflammation of adipocytes in association with the induction of metabolic disorders subsequent to obesity. Thus, AIM is involved in the progression of MetS in both an advancing and inhibitory fashion. Regulation of AIM could therefore be therapeutically applicable for MetS. PMID- 21970840 TI - Cilostazol to overcome high on-treatment platelet reactivity in korean patients treated with clopidogrel and calcium-channel blocker. PMID- 21970841 TI - Osteocytes, RANKL and bone loss. PMID- 21970842 TI - SSRIs associated with fracture risk. PMID- 21970843 TI - Unprecedented reactivity of an aluminium hydride complex with ArNH2BH3: nucleophilic substitution versus deprotonation. AB - Reaction of DIPPnacnacAlH(2) with DIPPNH(2)BH(3) did not give the anticipated deprotonation but nucleophilic substitution at B was observed instead. The product DIPPnacnacAl(BH(4))(2) was isolated and structurally characterized. Nucleophilic displacement at B might play a role in mechanistic pathways related to metal amidoborane complexes. PMID- 21970844 TI - Insulin sensitivity in response to a single resistance exercise session in apparently healthy individuals. AB - BACKGROUND: Regular resistance exercise completed for a number of weeks has been shown to increase insulin sensitivity and reduce the risk of diabetes-related complications. However, the acute responses to resistance exercise have not been adequately investigated in relation to training frequency. AIM: To investigate the changes to insulin sensitivity in apparently healthy individuals following a single session of unaccustomed resistance exercise. SUBJECTS AND METHODS: Ten sedentary, apparently healthy individuals performed a baseline oral glucose tolerance test and maximal strength testing. Participants then performed a single session of moderate-high intensity resistance exercise which was followed by 4 consecutive days of oral glucose tolerance testing, for which participants replicated their initial diet. Mean estimated insulin sensitivity change scores from baseline values and their 95% confidence intervals were compared to the previously determined values for a clinically meaningful change. RESULTS: Two participants were identified as having hyperinsulinemia and their data were therefore removed from the main analysis. There was a clinically meaningful increase in insulin response (mean >7237 pmol.l-1.120 min-1) on all days following the exercise session and a clinically meaningful increase in glucose response (mean >81 mmol.l-1.120 min-1) on only the 3rd day following exercise. These changes suggest a potentially adverse short-term effect. Additionally, the 2 individuals with hyperinsulinemia displayed more extreme results. CONCLUSION: These results suggest that insulin sensitivity may be impaired following a single session of unaccustomed resistance exercise for approximately 4 days in healthy untrained, older individuals. Further research is required for individuals with hyperinsulinemia. PMID- 21970845 TI - Transmission through a quantum dot molecule embedded in an Aharonov-Bohm interferometer. AB - We study theoretically the transmission through a quantum dot molecule embedded in the arms of an Aharonov-Bohm four quantum dot ring threaded by a magnetic flux. The tunable molecular coupling provides a transmission pathway between the interferometer arms in addition to those along the arms. From a decomposition of the transmission in terms of contributions from paths, we show that antiresonances in the transmission arise from the interference of the self-energy along different paths and that application of a magnetic flux can produce the suppression of such antiresonances. The occurrence of a period of twice the quantum of flux arises at the opening of the transmission pathway through the dot molecule. Two different connections of the device to the leads are considered and their spectra of conductance are compared as a function of the tunable parameters of the model. PMID- 21970846 TI - On Lamb and Rayleigh wave convergence in viscoelastic tissues. AB - Characterization of the viscoelastic material properties of soft tissue has become an important area of research over the last two decades. Our group has been investigating the feasibility of using a shear wave dispersion ultrasound vibrometry (SDUV) method to excite Lamb waves in organs with plate-like geometry to estimate the viscoelasticity of the medium of interest. The use of Lamb wave dispersion ultrasound vibrometry to quantify the mechanical properties of viscoelastic solids has previously been reported. Two organs, the heart wall and the spleen, can be readily modeled using plate-like geometries. The elasticity of these two organs is important because they change in pathological conditions. Diastolic dysfunction is the inability of the left ventricle (LV) of the heart to supply sufficient stroke volumes into the systemic circulation and is accompanied by the loss of compliance and stiffening of the LV myocardium. It has been shown that there is a correlation between high splenic stiffness in patients with chronic liver disease and strong correlation between spleen and liver stiffness. Here, we investigate the use of the SDUV method to quantify the viscoelasticity of the LV free-wall myocardium and spleen by exciting Rayleigh waves on the organ's surface and measuring the wave dispersion (change of wave velocity as a function of frequency) in the frequency range 40-500 Hz. An equation for Rayleigh wave dispersion due to cylindrical excitation was derived by modeling the excised myocardium and spleen with a homogenous Voigt material plate immersed in a nonviscous fluid. Boundary conditions and wave potential functions were solved for the surface wave velocity. Analytical and experimental convergence between the Lamb and Rayleigh waves is reported in a finite element model of a plate in a fluid of similar density, gelatin plate and excised porcine spleen and left ventricular free-wall myocardium. PMID- 21970847 TI - Management of cerebrospinal fluid leaks after vestibular schwannoma surgery. AB - OBJECTIVE: To evaluate the incidence and treatment of cerebrospinal fluid (CSF) leaks after resection of vestibular schwannomas and to propose a treatment algorithm for their management. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Review of 1,922 subjects who underwent resection of vestibular schwannomas from 1970 to 2010. INTERVENTION: Surgical resection of vestibular schwannoma. MAIN OUTCOME MEASURES: Patient demographics, surgical approach used, CSF leak incidence, meningitis, treatment, and success in the management of CSF leaks. RESULTS: Postoperative CSF leaks were observed in 12.9% of our patients. There was no significant difference between the type of approach and the presence of CSF leak with translabyrinthine, suboccipital and middle fossa CSF leak rates of 12%, 12%, and 13%, respectively (p = 0.07). Patients presented with a wound leak or rhinorrhea almost equally. Ultimately, 92% of patients with rhinorrhea underwent surgical intervention. The probability of a patient with rhinorrhea requiring a second intervention was higher when the initial intervention was conservative rather than surgical. However, the probability of a patient with a wound leak requiring a second intervention was essentially the same when initially treated conservatively or surgically. CONCLUSION: Our data suggests that there is no difference in CSF leak rates between the different surgical approaches. The appropriate treatment strategy is dependent on the presentation of the CSF. Although conservative treatment is effective for managing wound leaks, it is less effective in managing patients with rhinorrhea. Therefore, surgical treatments should play an early role in the treatment algorithm of patients with CSF rhinorrhea. PMID- 21970848 TI - Bilateral third and fourth windows of the inner ear. PMID- 21970849 TI - Langerhans cell histiocytosis of the temporal bone. PMID- 21970850 TI - Sudden brief unilateral tapering tinnitus: prevalence and properties. AB - OBJECTIVE: To systematically characterize unilateral tinnitus typically lasting less than a minute. STUDY DESIGN: Observational study. SETTING: Outpatient clinic in a tertiary referral hospital. PATIENTS: Study I: 62 unselected adults. Study II: 74 adults with sudden brief unilateral tapering tinnitus (SBUTT). INTERVENTIONS: Study I: Structured interview regarding SBUTTs and other types of tinnitus. Study II: Maintaining an SBUTT log for 4 consecutive months. MAIN OUTCOME MEASURES: Study I: Retrospective prevalence of SBUTTs. Study II: Prospective frequency and characteristics of SBUTTs. RESULTS: Study I: 76% of the participants recalled having at least one SBUTT in the past. There was no significant difference in the incidence of SBUTTs with respect to handedness, age, sex, the presence or absence of chronic tinnitus, whether tinnitus could be brought on by exposure to loud sounds, or whether auditory perception could be modulated with strong muscle contractions of the neck or jaw. Study II: SBUTTs mean rate was 1.2 per month (range, 0-11.5). The rate in people with chronic tinnitus was twice that of those without chronic tinnitus. Right ear SBUTTs predominated nearly 2 to 1. Pitch estimates ranged between 0.1 and 4.4 kHz; 75% of SBUTTs lasted 25 seconds or less. A quarter occurred with simultaneous ear fullness. CONCLUSION: In the 76% of adults with SBUTTs, the average rate of occurrence was about once a month. SBUTTs are twice as common for the right ear as the left. One of 4 SBUTTs occurs with ear fullness. A quarter of adults never recalled ever having an SBUTT. PMID- 21970852 TI - Erlotinib as maintenance therapy in patients with advanced non-small cell lung cancer: a pooled analysis of three randomized trials. AB - Three randomized trials (SATURN, ATLAS and IFCT-GFPC 0502) have demonstrated that the oral antiepidermal growth factor receptor tyrosine kinase inhibitor erlotinib can improve progression-free survival (PFS) and overall survival (OS), as maintenance therapy after first-line chemotherapy in advanced non-small cell lung cancer. We pooled the results of these three trials by performing a meta-analysis of hazard ratios (HRs) and the 95% confidence intervals (CIs) for the PFS and the OS for maintenance erlotinib versus observation, standard therapy or placebo. The benefits in the predefined subgroups of patients [according to histology, sex, performance status (PS), and smoking status] were assessed. The OS was superior in the 963 patients treated with erlotinib than in the 979 nontreated patients [HR=0.87 (P=0.003), corresponding to a 13% reduction in the risk of death. The pooled HR for the PFS is 0.76 (P<0.00001), corresponding to a 24% lower risk of being progression free]. All the patients in the subgroup analysis experienced a benefit from erlotinib and, in particular, never-smoking women with nonsquamous histology with a PS of 0. Both responders and those with stable disease obtain PFS benefit. The addition of maintenance erlotinib significantly improves PFS and OS in patients with advanced non-small cell lung cancer who had not progressed after four cycles of first-line chemotherapy. The benefit does not seem to be limited to a particular subgroup, although it is more pronounced in never-smoking women patients with nonsquamous carriers with a PS of 0. PMID- 21970851 TI - Targeting of nanoparticles in cancer: drug delivery and diagnostics. AB - Anticancer agents continue to be a preferred therapeutic option for several malignancies. Despite their effectiveness, oncologists are continually looking for tumor-specific anticancer agents to prevent adverse effects in patients. Targeting of imaging agents to cancerous tissue is another area that is enthusiastically explored to circumvent some of the drawbacks that current imaging agents possess, including the inability to target small tumor cells, inadequate imaging period, and the risk of renal damage. Formulation scientists have explored nanotechnology-based delivery systems for targeting anticancer agents and tumor-imaging agents to cancer tissue. Targeting with nanotechnology based delivery systems has been investigated by both passive and active mechanisms with significant clinical success. This review presents a discussion on targeting strategies used for the delivery of nanoparticles by passive and active mechanisms, focusing more specifically on active targeting of nanoparticles using albumin, folic acid, transferrin, and aptamers as targeting ligands. PMID- 21970853 TI - Wound healing and catheter thrombosis after implantable venous access device placement in 266 breast cancers treated with bevacizumab therapy. AB - The aim of this study was to determine, in a population with metastatic breast cancer treated with bevacizumab therapy, the incidence of wound dehiscence after placement of an implantable venous access device (VAD) and to study the risk of catheter thrombosis. This study enrolled all VADs placed by 14 anesthetists between 1 January 2007 and 31 December 2009: 273 VADs in patients treated with bevacizumab therapy and 4196 VADs in patients not treated with bevacizumab therapy. In the bevacizumab therapy group, 13 cases of wound dehiscence occurred in 12 patients requiring removal of the VAD (4.76%). All cases of dehiscence occurred when bevacizumab therapy was initiated less than 7 days after VAD placement. Bevacizumab therapy was initiated less than 7 days after VAD placement in 150 cases (13 of 150: 8.6%). The risk of dehiscence was the same from 0 to 7 days. In parallel, the VAD wound dehiscence rate in patients not receiving bevacizumab therapy was eight of 4197 cases (0.19%) (Fisher's test significant, P<0.001). No risk factors of dehiscence were identified: anesthetists, learning curves, and irradiated patients. VAD thrombosis occurred in four patients (1.5%). In parallel, VAD thrombosis occurred in 51 of 4197 patients (1.2%) not receiving bevacizumab therapy (Fisher's test not significant; P=0.43). Bevacizumab therapy was permanently discontinued in five patients related to wound dehiscence and in one patient due to extensive skin necrosis. These data suggest the need to observe an interval of at least 7 days between VAD placement and initiation of bevacizumab therapy to avoid the risk of a wound dehiscence requiring chest wall port explant. The risk of VAD thrombosis does not require any particular primary prevention. PMID- 21970854 TI - Long-term remission in a patient with heavily pretreated, advanced ovarian cancer achieved by bevacizumab and metronomic cyclophosphamide treatment. AB - Vascular endothelial growth factor seems to be a promoter of tumor progression for epithelial ovarian cancer. New drugs such as bevacizumab, either alone or in combination with metronomic chemotherapy, suppress tumor growth and have proved to be effective in various tumor types. We present a 60-year-old patient with heavily pretreated, recurrent epithelial ovarian cancer, who received bevacizumab (10 mg/m(2)) every 2 weeks in combination with metronomic administered low-dose cyclophosphamide (50 mg/day orally) after failing four explorative laparotomies and multiple chemotherapy regimes. At the time of writing, February 2011, she was being treated with this combination therapy for 24 months and the progression free survival still continues. Treatment of advanced, refractory epithelial ovarian cancer with bevacizumab in combination with low-dose cyclophosphamide could be a very effective salvage treatment option in heavily pretreated patients. PMID- 21970855 TI - Blockade of fatty acid synthase induces ubiquitination and degradation of phosphoinositide-3-kinase signaling proteins in ovarian cancer. AB - Aberrations within the phosphoinositide-3-kinase (PI3K) pathway occur in greater than 45% of ovarian carcinomas. The PI3K cascade transmits signals from ErbB receptors downstream to S6 and 4EBP1, which are involved in protein biosynthesis. Many ovarian carcinomas reveal hyperactivation of ErbB1 (epidermal growth factor receptor) or ErbB2 (HER2/neu). Unfortunately, the benefit of anti-ErbB drugs is yet rather limited in ovarian carcinomas. Thus, novel targeting strategies are needed for ovarian carcinomas. The lipogenic enzyme fatty acid synthase (FASN) is overexpressed in approximately 80% of ovarian carcinomas. It stimulates cell growth and signifies poor prognosis. FASN inhibition impedes (ErbB) membrane receptor signaling and sensitizes cells against anti-ErbB drugs. Here, we show that the FASN inhibitor C75 and FASN-targeting siRNAs abrogate growth, induce apoptosis, and downregulate phosphorylation/expression of the PI3K effectors AKT, mTOR, p70S6K, S6, and 4EBP1. In contrast, FASN inhibition impairs expression but only weakly affects phosphorylation of ERK1/2 mitogen-activated protein kinases in ovarian carcinoma cells. Cycloheximide-mediated blockade of protein translation reveals that C75- or FASN siRNA-induced shutdown of FASN accelerates decomposition of signaling proteins. This effect is caused by C75- or FASN siRNA dependent stimulation of ubiquitination followed by lysosomal-autophagosomal proteolysis. In contrast, PI3K inhibitor LY294002 blocks phosphorylation but does not reduce expression/stability of PI3K effectors. Forced expression of hyperactive (HA) AKT1, unlike HA-MEK1, impairs the growth-inhibitory action of C75. We provide first evidence that the anticancer action of FASN inhibitors is at least partially mediated by drug-dependent proteolysis of PI3K effectors. FASN is a promising cancer target, whose inhibition not only abrogates lipogenesis, which is indispensable for cancer growth, but also downregulates oncogenic PI3K signaling. PMID- 21970856 TI - Understanding the dual nature of CD44 in breast cancer progression. AB - CD44 has been the subject of extensive research for more than 3 decades because of its role in breast cancer, in addition to many physiological processes, but interestingly, conflicting data implicate CD44 in both tumor suppression and tumor promotion. CD44 has been shown to promote protumorigenic signaling and advance the metastatic cascade. On the other hand, CD44 has been shown to suppress growth and metastasis. Histopathological studies of human breast cancer have correlated CD44 expression with both favorable and unfavorable clinical outcomes. In recent years, CD44 has garnered significant attention because of its utility as a stem cell marker and has surfaced as a potential therapeutic target, necessitating a greater understanding of CD44 in breast cancer. In this review, we attempt to unify the literature implicating CD44 in both tumor promotion and suppression, and explain its dualistic nature. PMID- 21970858 TI - Quantitative prediction of intestinal glucuronidation of drugs in rats using in vitro metabolic clearance data. AB - UDP-glucuronosyltransferase (UGT) is highly expressed in the small intestine and catalyzes the glucuronidation of small molecules, which may affect the oral bioavailability of drugs. However, no method of predicting the in vivo observed fraction of absorbed drug (F(a)F(g)) affected by UGT has yet been established. Here, we investigated the relationship between F(a)F(g) and in vitro clearance of nine UGT substrates (ketoprofen, tolcapone, telmisartan, raloxifene, entacapone, resveratrol, buprenorphine, quercetin, and ezetimibe) via UGT in intestinal microsomes (CL(int, UGT)) in rats. F(a)F(g) was calculated from pharmacokinetic parameters after intravenous and oral administration or using the portal-systemic concentration difference method, with values ranging from 0.027 (ezetimibe) to 1 (tolcapone). Glucuronides of model compounds were observed in the portal plasma after oral administration, with CL(int, UGT) values ranging from 57.8 (tolcapone) to 19,200 uL/min/mg (resveratrol). An inverse correlation between F(a)F(g) and CL(int, UGT) was observed for most compounds and was described using a simplified intestinal availability model reported previously. This model gave accurate predictions of F(a)F(g) values for three in-house compounds. Our results show that F(a)F(g) in rats is affected by UGT and can be predicted using CL(int, UGT). This work should hasten the development of a method to predict F(a)F(g) in humans. PMID- 21970859 TI - Risk factors associated with high glycated hemoglobin levels (>=5.7%) in Korean adults with normal fasting glucose. AB - BACKGROUND: Early detection of high risk for Type 2 diabetes (T2DM) and early diagnosis of T2DM are fundamental for the prevention of diabetes and associated complications. AIM: To identify the major predictors of high glycated hemoglobin (HbA(1C)) levels in people with normal fasting glucose levels. SUBJECTS AND METHODS: This was a cross-sectional study involving 8035 adults aged >=20 yr. Multivariate logistic regression analyses were performed to estimate the odds ratios (OR) of clinical risk factors for high HbA(1C) (>=5.7%) in the subjects with normal fasting glucose levels (<100 mg/dl). RESULTS: Except for fasting glucose levels, age, and total cholesterol levels were significantly associated with HbA(1C) levels. After adjustment for gender, fasting glucose, and behavioral factors, OR for high HbA(1C) levels for age (>=40 yr old) and high total cholesterol levels (>=200 mg/dl) were 2.27 (95% CI: 2.01-2.56) and 1.76 (95% CI: 1.56-1.97), respectively. Each OR was higher than that of metabolic syndrome (MS) (OR=1.59, 95% CI: 1.34- 1.87). Coexistence of both factors had a higher OR (OR=2.40, 95% CI: 2.11-2.72) for high HbA(1C) levels when compared to each factor alone. CONCLUSIONS: HbA(1C) was significantly associated with fasting glucose, age, and total cholesterol levels. In subjects with normal fasting glucose levels, age of over 40 yr or high total cholesterol levels (>=200 mg/dl) is more predictive of high HbA(1C) levels than MS. These findings suggest that both factors might be better predictors than MS for the screening of pre-diabetes or diabetes in clinical practice. PMID- 21970860 TI - Selective mutism: a team approach to assessment and treatment in the school setting. AB - The school nurse plays a pivotal role in the assessment and treatment of selective mutism (SM), a rare disorder found in elementary school children. Due to anxiety, children with SM do not speak in uncomfortable situations, primarily the school setting. Diagnosis of SM is often missed in the formative years because the child does speak at home. Early diagnosis and treatment provide the key to addressing this rare disorder. The school nurse plays a critical role as a member of the Instructional Support Team (IST). The school nurse, as team liaison, provides communication between parents, school staff, and medical personnel. School nurses make a difference by advocating for the child with SM and possessing the necessary knowledge to effectively intervene. This article discusses a team approach to the assessment and treatment of SM and the role of the school nurse in the school setting. PMID- 21970857 TI - Loss of Trop2 promotes carcinogenesis and features of epithelial to mesenchymal transition in squamous cell carcinoma. AB - Trop2, an oncogenic cell surface protein under investigation as a therapeutic target, is commonly overexpressed in several epithelial tumor types yet its function in tumor biology remains relatively unexplored. To investigate the role of Trop2 in epithelial carcinogenesis, we generated Trop2(-/-) mice, which are viable and possess a normal lifespan. Contrary to expectations, Trop2 loss fails to suppress keratinocyte transformation. Instead, ras-transformed Trop2(-/-) keratinocytes preferentially pass through an epithelial to mesenchymal transition (EMT) and form tumors with spindle cell histology. Furthermore, Trop2 loss renders Arf-null mice susceptible to the formation of biphasic sarcomatoid carcinomas containing both squamous and spindle cell components upon carcinogen exposure in an otherwise skin cancer-resistant strain (C57BL/6). Immortalized keratinocytes derived from Trop2(-/-)Arf(-/-) mice exhibit enhanced proliferative and migratory capacity as well as increased activation of mitogen-activated protein kinase and Src prior to transformation. The clinical relevance of these findings was supported by studying the molecular epidemiology of Trop2 in primary head and neck squamous cell carcinomas. This analysis revealed that Trop2 mRNA levels are decreased in a subset of tumors with features of EMT, and total loss of Trop2 protein expression is observed in the spindle cell component of sarcomatoid carcinomas. Therefore, while previous studies have emphasized the potential importance of Trop2 gain of function, these results uncover a role for Trop2 loss in tumorigenesis and the mesenchymal transdifferentiation observed in a subset of squamous cell carcinomas. PMID- 21970861 TI - Outcomes of an elementary school-based vision screening program in North Carolina. AB - School nurses can play a key role in the detection of significant refractive error. The purpose of this study was to assess the impact of a statewide school nurse vision screening program by evaluating the outcomes of screening among first, third, and fifth graders in 10 schools in North Carolina during the 2009 2010 school year. Of the 2,726 children who were screened, 7.7% (n = 209) were abnormal, of which 89% (n = 186) were placed into a comprehensive database for follow-up. No documentation of any follow-up was available for 35% (n = 65) of these children. Of the 106 with complete eye examination data available, 54.7% (n = 58) had myopia, 22.6% (n = 24) had hyperopia, 11.3% (n = 12) had astigmatism, 1.9% (n = 2) had anisometropia, and 9.4% (n = 10) were normal. Even with incomplete follow-up, this screening activity led to identification of 3 cases for every 100 children screened, underscoring the importance of high-quality school-based vision screening programs. PMID- 21970862 TI - Treatment fidelity of motivational interviewing delivered by a school nurse to increase girls' physical activity. AB - Motivational interviewing, which involves the use of person-centered, directive counseling techniques, shows promise for changing adolescent behaviors. The purpose of this article was to describe the methodology and findings related to the treatment fidelity of three face-to-face motivational interviewing sessions involving middle school girls and a school nurse to help the girls increase their moderate-to-vigorous physical activity. The following four areas related to treatment fidelity were addressed: (a) study design, (b) training of interventionists, (c) intervention delivery, and (d) intervention receipt. Findings showed that 34 of 37 (91.9%) girls completed all three sessions. An initial motivational interviewing training workshop followed by evaluation of audiotaped sessions with constructive feedback can result in successful and consistent delivery by a school nurse. PMID- 21970863 TI - Raman spectroscopy of CaSnO3 at high temperature: a highly quasi-harmonic perovskite. AB - Calcium stannate perovskite (CaSnO(3)) has been studied by Raman spectroscopy at two excitation wavelengths (514.5 and 632.8 nm). No phase transition was observed. Rather, the thermal evolution of the Raman lines showed a high degree of harmonicity with small Gruneisen parameters and thermal line broadening following Gamma=Acoththeta/T, where the quantum temperature theta is determined by the phonon branch without further coupling with other degrees of freedom. The geometrical nature of phonon lines has been identified. High-temperature powder x ray diffraction measurements provide thermal expansion coefficients of alpha(x)=13.9 * 10(-6) K(-1), alpha(y)=2.7 * 10(-6) K(-1), alpha(z)=14.3 * 10(-6) K(-1). The strongly quasi-harmonic behaviour observed and the lack of any indication of instability with respect to the post-perovskite structure points to the strongly first-order character of the reported perovskite to post-perovskite phase transition in this material, which appears to behave as a very good analogue to MgSiO(3) in the Earth's interior. PMID- 21970864 TI - Fast and efficient fully 3D PET image reconstruction using sparse system matrix factorization with GPU acceleration. AB - Statistically based iterative image reconstruction has been widely used in positron emission tomography (PET) imaging. The quality of reconstructed images depends on the accuracy of the system matrix that defines the mapping from the image space to the data space. However, an accurate system matrix is often associated with high computation cost and huge storage requirement. In this paper, we present a method to address this problem using sparse matrix factorization and graphics processor unit (GPU) acceleration. We factor the accurate system matrix into three highly sparse matrices: a sinogram blurring matrix, a geometric projection matrix and an image blurring matrix. The geometrical projection matrix is precomputed based on a simple line integral model, while the sinogram and image blurring matrices are estimated from point source measurements. The resulting factored system matrix has far less nonzero elements than the original system matrix, which substantially reduces the storage and computation cost. The smaller matrix size also allows an efficient implementation of the forward and backward projectors on a GPU, which often has a limited memory space. Our experimental studies show that the proposed method can dramatically reduce the computation cost of high-resolution iterative image reconstruction, while achieving better performance than existing factorization methods. PMID- 21970865 TI - Transplantation: Host stem cells boost tolerance of liver grafts. PMID- 21970866 TI - Nutrition: Different feeding regimens could affect the development of necrotizing enterocolitis in preterm neonates. PMID- 21970868 TI - Neurogastroenterology: Improving 3D imaging of the enteric nervous system. PMID- 21970869 TI - IBD: Genetics of IBD in asian populations. PMID- 21970867 TI - Assessment and management of obesity in childhood and adolescence. AB - The increased prevalence of obesity in childhood and adolescence highlights the need for effective treatment approaches. Initial assessments of these patients should include taking a careful history (investigating comorbidities, family history and potentially modifiable behaviors) and physical examination with BMI plotted on a BMI-for-age chart. The degree of investigation is dependent on the patient's age and severity of obesity, the findings on history and physical examination, and associated familial risk factors. There are several broad principles of conventional management: management of comorbidities; family involvement; taking a developmentally appropriate approach; the use of a range of behavior change techniques; long-term dietary change; increased physical activity; and decreased sedentary behaviors. Orlistat can be useful as an adjunct to lifestyle changes in severely obese adolescents and metformin can be used in older children and adolescents with clinical insulin resistance. Bariatric surgery should be considered in those who are severely obese, with recognition of the need for management in centers with multidisciplinary weight management teams and for surgery to be performed in tertiary institutions experienced in bariatric surgery. Finally, given the high prevalence and chronic nature of obesity, coordinated models of care for health-service delivery for the management of pediatric obesity are needed. PMID- 21970870 TI - Acute pancreatitis: Is smoking a risk factor for acute pancreatitis? PMID- 21970871 TI - Optimization of conventional therapy in patients with IBD. AB - The majority of patients with IBD use conventional therapy (namely, aminosalicylates, antibiotics, corticosteroids and immunomodulatory agents) for prolonged periods of time, to both induce and maintain remission. Treatment paradigms in IBD have evolved towards a rapid escalation of therapy to achieve stringent goals, including mucosal healing and a reduction in the need for hospital admission and surgery. In this context, the failure to optimize conventional therapy can lead to a potentially effective treatment being abandoned too early, which is undesirable when only a limited number of drugs are effective in the management of IBD, and could also lead to patients being unnecessarily exposed to potentially toxic and/or expensive biologic drugs. This Review provides an overview of the many ways in which conventional therapy can be optimized, and describes strategies to improve adherence to drug regimens, such as simplifying the dosing regimen, optimizing drug delivery and dose, and tailoring medication on the basis of metabolite levels. PMID- 21970873 TI - Expression and prognostic value of transcription factor PROX1 in colorectal cancer. AB - BACKGROUND: PROX1 is a specific target of the beta-catenin/TCF pathway in the intestinal epithelium. It acts as a regulator of progression from a benign to a highly dysplastic phenotype in colorectal tumours. However, the clinical significance of PROX1 expression is not known. METHODS: We studied the prognostic value of immunohistochemical expression of PROX1 in a series of 517 patients with colorectal cancer (CRC). RESULTS: The majority of the tumour samples expressed PROX1 (91%, 471 out of 517). High PROX1 expression was associated with a poor grade of tumour differentiation (P<0.0001). In the subgroup of patients with colon cancer, high PROX1 expression was associated with unfavourable colorectal cancer-specific survival (CCSS) as compared with low PROX1 expression (CCSS 47% vs 62%; P=0.045; RR 1.47). The association between high PROX1 and poor outcome was further strengthened in female colon cancer patients (CCSS 38% vs 63%; P=0.007; RR 2.02). Nonetheless, in multivariate survival analysis PROX1 expression was not retained as an independent prognostic factor. CONCLUSION: High PROX1 expression is associated with a poor grade of tumour differentiation, and, in colon cancer patients, also with less favourable patient outcome. Our results strengthen the previous preclinical observations that PROX1 has a role in tumour progression in CRC. PMID- 21970872 TI - Risks versus benefits of gastrointestinal endoscopy during pregnancy. AB - Although gastrointestinal endoscopy is generally safe, its safety must be separately analyzed during pregnancy with regard to fetal safety. Fetal risks from endoscopic medications are minimized by avoiding FDA category D drugs, minimizing endoscopic medications, and anesthesiologist attendance at endoscopy. Esophagogastroduodenoscopy seems to be relatively safe for the fetus and may be performed when strongly indicated during pregnancy. Despite limited clinical data, endoscopic banding of esophageal varices and endoscopic hemostasis of nonvariceal upper gastrointestinal bleeding seems justifiable during pregnancy. Flexible sigmoidoscopy during pregnancy also appears to be relatively safe for the fetus and may be performed when strongly indicated. Colonoscopy may be considered in pregnant patients during the second trimester if there is a strong indication. Data on colonoscopy during the other trimesters are limited. Therapeutic endoscopic retrograde cholangiopancreatography seems to be relatively safe during pregnancy and should be performed for strong indications (for example, complicated choledocholithiasis). Endoscopic safety precautions during pregnancy include the performance of endoscopy in hospital by an expert endoscopist and only when strongly indicated, deferral of endoscopy to the second trimester whenever possible, and obstetric consultation. PMID- 21970874 TI - Preclinical emergence of vandetanib as a potent antitumour agent in mesothelioma: molecular mechanisms underlying its synergistic interaction with pemetrexed and carboplatin. AB - BACKGROUND: Although pemetrexed, a potent thymidylate synthase (TS) inhibitor, enhances the cytoytoxic effect of platinum compounds against malignant pleural mesothelioma (MPM), novel combinations with effective targeted therapies are warranted. To this end, the current study evaluates new targeted agents and their pharmacological interaction with carboplatin-pemetrexed in human MPM cell lines. METHODS: We treated H2052, H2452, H28 and MSTO-211H cells with carboplatin, pemetrexed and targeted compounds (gefitinib, erlotinib, sorafenib, vandetanib, enzastaurin and ZM447439) and evaluated the modulation of pivotal pathways in drug activity and cancer cell proliferation. RESULTS: Vandetanib emerged as the compound with the most potent cytotoxic activity, which interacted synergistically with carboplatin and pemetrexed. Drug combinations blocked Akt phosphorylation and increased apoptosis. Vandetanib significantly downregulated epidermal growth factor receptor (EGFR)/Erk/Akt phosphorylation as well as E2F-1 mRNA and TS mRNA/protein levels. Moreover, pemetrexed decreased Akt phosphorylation and expression of DNA repair genes. Finally, most MPM samples displayed detectable levels of EGFR and TS, the variability of which could be used for patients' stratification in future trials with vandetanib-pemetrexed carboplatin combination. CONCLUSION: Vandetanib markedly enhances pemetrexed carboplatin activity against human MPM cells. Induction of apoptosis, modulation of EGFR/Akt/Erk phosphorylation and expression of key determinants for pemetrexed and carboplatin activity contribute to this synergistic interaction, and, together with the expression of these determinants in MPM samples, warrant further clinical investigation. PMID- 21970875 TI - A combination of serum leucine-rich alpha-2-glycoprotein 1, CA19-9 and interleukin-6 differentiate biliary tract cancer from benign biliary strictures. AB - BACKGROUND: Biliary tract cancer (BTC) and benign biliary strictures can be difficult to differentiate using standard tumour markers such as serum carbohydrate antigen 19-9 (CA19-9) as they lack diagnostic accuracy. METHODS: Two dimensional difference gel electrophoresis and tandem mass spectrometry were used to profile immunodepleted serum samples collected from cases of BTC, primary sclerosing cholangitis (PSC), immunoglobulin G4-associated cholangitis and healthy volunteers. The serum levels of one candidate protein, leucine-rich alpha 2-glycoprotein (LRG1), were verified in individual samples using enzyme-linked immunosorbent assay and compared with serum levels of CA19-9, bilirubin, interleukin-6 (IL-6) and other inflammatory markers. RESULTS: We report increased LRG1, CA19-9 and IL-6 levels in serum from patients with BTC compared with benign disease and healthy controls. Immunohistochemical analysis also demonstrated increased staining of LRG1 in BTC compared with cholangiocytes in benign biliary disease. The combination of receiver operating characteristic (ROC) curves for LRG1, CA19-9 and IL-6 demonstrated an area under the ROC curve of 0.98. In addition, raised LRG1 and CA19-9 were found to be independent predictors of BTC in the presence of elevated bilirubin, C-reactive protein and alkaline phosphatase. CONCLUSION: These results suggest LRG1, CA19-9 and IL-6 as useful markers for the diagnosis of BTC, particularly in high-risk patients with PSC. PMID- 21970876 TI - Anti-tumour activity of afatinib, an irreversible ErbB family blocker, in human pancreatic tumour cells. AB - BACKGROUND: The combination of the reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib with gemcitabine obtained FDA approval for treating patients with pancreatic cancer. However, duration of response is often limited and there is currently no reliable predictive marker. METHODS: We determined the sensitivity of a panel of human pancreatic tumour cell lines to treatment with afatinib, erlotinib, monoclonal antibody (mAb) ICR62, and gemcitabine, using the Sulforhodamine B colorimetric assay. The effect of these agents on cell signalling and cell-cycle distribution was determined by western blot and flow cytometry, respectively. RESULTS: At 200 nM, ICR62 had no effect on growth of these tumour cells with the exception of BxPC-3 cells. BxPC-3 cells were also sensitive to treatment with afatinib and erlotinib with respective IC(50) values of 11 and 1200 nM. Compared with erlotinib, afatinib was also more effective in inhibiting the growth of the other human pancreatic tumour cell lines and in blocking the EGF-induced phosphorylation of tyrosine, EGFR, MAPK, and AKT. When tested in BxPC-3 xenografts, afatinib induced significant delay in tumour growth. CONCLUSION: The superiority of afatinib in this study encourages further investigation on the therapeutic potential of afatinib as a single agent or in combination with gemcitabine in pancreatic cancer. PMID- 21970877 TI - Comparing cancer mortality and GDP health expenditure in England and Wales with other major developed countries from 1979 to 2006. AB - BACKGROUND: Cancer and gross-domestic-product on health expenditure (GDPHE) are critical issues for major developed countries (MDC). Each country's economic input, GDPHE 1980-2005 is contrasted with clinical outputs, cancer mortality rates (CMRs), to compare their efficiency and effectiveness in reducing CMR. METHODS: World Health Organization's CMR data for baseline years (1979-1981) are compared with 2004-2006 by sex and age. The chi(2)-tests are used to determine differences between MDC. Efficiency is analysed by calculating a ratio of average GDPHE to reduced CMR over the period. RESULTS: Inputs: All the countries GDPHE grew substantially. For the United Kingdom this reached 9.3%, which is below the MDC average (10%). Outputs: CMR fell substantially (>20%) in six of the ten countries. The male average (15-74 years) CMR in England and Wales had been third highest but by 2004-2006 was sixth, a 31% reduction, which was significantly greater than seven other countries. Initially England and Wales female average CMR was the highest of all countries and is now the second highest. There were significantly greater reductions for the 55-64 and 65-74 years old than in seven and four countries, respectively. GDPHE reduced CMR ratios--the average GDPHE:reduced CMR ratio of England and Wales was 1:120, greater than all MDC and double that in four countries. CONCLUSION: Comparing GDPHE input with CMR output showed that relatively the NHS achieved more with proportionately less than other MDC. PMID- 21970878 TI - Detection of circulating tumour cells with a hybrid (epithelial/mesenchymal) phenotype in patients with metastatic non-small cell lung cancer. AB - BACKGROUND: Circulating tumour cells (CTC) have a crucial role in metastasis formation and can consistently provide information on patient prognosis. Epithelial-mesenchymal transition (EMT) is considered as an essential process in the metastatic cascade, but there is currently very few data demonstrating directly the existence of the EMT process in CTCs. METHODS: CTCs were enriched by blood filtration using ISET (isolation by size of epithelial tumour cells), triply labelled with fluorescent anti-vimentin, anti-pan-keratin antibodies and SYTOX orange nuclear dye, and examined by confocal microscopy in six patients with metastatic non-small cell lung cancer (NSCLC). In parallel, CTCs were morphocytologically identified by an experienced cytopathologist. RESULTS: Isolated or clusters of dual CTCs strongly co-expressing vimentin and keratin were evidenced in all patients (range 5-88/5 ml). CTCs expressing only vimentin were detected in three patients, but were less frequent (range 3-15/5 ml). No CTC expressing only keratin was detected. CONCLUSION: We showed for the first time the existence of hybrid CTCs with an epithelial/mesenchymal phenotype in patients with NSCLC. Their characterisation should provide further insight on the significance of EMT in CTCs and on the mechanism of metastasis in patients with NSCLC. PMID- 21970879 TI - Influence of eicosapentaenoic acid supplementation on lean body mass in cancer cachexia. AB - Cancer cachexia is characterised by a progressive loss of muscle, resulting in functional impairment and shorter survival. Eicosapentaenoic acid, an n-3 polyunsaturated fatty acid found in fish, has been studied for its role as an anti-cachexia therapy. Initial results of eicosapentaenoic supplementation in advanced cancer were promising with improvements in lean body mass (LBM), appetite and quality of life. However, subsequent larger phase III clinical trials reported minimal benefits of supplementation. Recently, several studies have used different study designs, which may provide insight on the effectiveness of eicosapentaenoic in cancer cachexia and also on potential sources of divergent results in previous trials. This review examines the potential benefit of eicosapentaenoic supplementation on LBM and discusses limitations with current studies to identify methods which may aid in progressing the research of future clinical trials. PMID- 21970880 TI - Ki 67 is a major, but not the sole determinant of Oncotype Dx recurrence score. AB - BACKGROUND: Immunohistological assessment of Ki 67 expression is less expensive than Oncotype Dx, which is currently used to identify patients with lymph node negative breast cancer, who will benefit from adjuvant chemotherapy. METHODS: The relationship of immunohistologically measured Ki 67 to Oncotype DX recurrence score (RS) was examined in 53 cases of T1-2 N0 M0 (oestrogen receptor-positive, HER2/neu negative) breast cancer. RESULTS: There was a strong linear correlation between Ki 67 value and the Oncotype Dx RS. All patients in the low Ki 67 group (Ki 67 of <= 10%) had Oncotype Dx RSs of low or intermediate risk. The vast majority of patients (93.8%) in the high-Ki 67 group (Ki 67 >= 25%) had oncotype RSs of high or intermediate risk. CONCLUSION: Ki 67 proliferation value is a major, but not the sole determinant of Oncotype Dx score. PMID- 21970881 TI - Acquired platinum resistance enhances tumour angiogenesis through angiotensin II type 1 receptor in bladder cancer. AB - BACKGROUND: We investigated the changes in reactive oxygen species (ROS) and angiogenesis through angiotensin II (Ang II) type 1 receptor (AT1R) after the development of acquired platinum resistance in bladder cancer. METHODS: Four invasive human bladder cancer cell lines, T24, 5637, T24PR, and 5637PR, were used in vitro, whereas in vivo, T24 and T24PR cells were used. T24PR and 5637PR cells were newly established at our institution as acquired platinum-resistant sublines by culturing in cisplatin (CDDP)-containing conditioned medium for 6 months. RESULTS: Ang II induced significantly higher vascular endothelial growth factor (VEGF) production in T24PR and 5637PR cells than in their corresponding parent cells in vitro, whereas Ang II induced a further increase in VEGF production. These platinum-resistant cells also showed significantly higher AT1R expression than their corresponding parent cells. ROS was also significantly upregulated in T24PR and 5637PR cells, whereas increased AT1R expression was significantly downregulated by scavenging free radicals. We also demonstrated the efficacy of AT1R blockade at suppressing the growth of platinum-resistant xenograft model. CONCLUSION: Our findings indicate a new molecular mechanism for upregulated AT1R signalling through increased ROS when tumours progressed after the CDDP-based regimens, and shed light on the importance of AT1R blockade for platinum resistant bladder cancers. PMID- 21970882 TI - Long-term survival of young women receiving fertility-sparing surgery for ovarian cancer in comparison with those undergoing radical surgery. AB - OBJECTIVES: To compare the clinical outcome of patients with stage I epithelial ovarian cancer (EOC) who received with fertility-sparing surgery (FSS) with those who underwent radical surgery (RS). METHODS: After a central pathological review and search of the medical records from multiple institutions, a total of 572 patients were retrospectively evaluated. All patients were divided into three groups: group A {FSS (n=74); age, <= 40}; groups B and C [RS; age, 40 >={(B), n=52}; 40<{(C), n=446}]. RESULTS: Five-year overall survival (OS) and disease free survival (DFS) rates of patients in the groups were as follows: group A, 90.8% (OS)/87.9% (DFS); group B, 88.3% (OS)/84.4% (DFS); group C, 90.6% (OS)/85.3% (DFS), respectively (OS, P=0.802; DFS, P=0.765). Additionally, there was no significant difference in OS and DFS among the three groups stratified to stage IA or IC (OS (IA), P=0.387; DFS (IA), P=0.314; OS (IC), P=0.993; DFS (IC), P=0.990, respectively). Furthermore, patients with a grade 1-2 or 3 tumours in the FSS group did not have a poorer prognosis than those in the RS group. CONCLUSIONS: Stage I EOC patients treated with FSS showed an acceptable prognosis compared with those who underwent RS. PMID- 21970883 TI - Expression of miR-487b and miR-410 encoded by 14q32.31 locus is a prognostic marker in neuroblastoma. AB - BACKGROUND: Combination of age at diagnosis, stage and MYCN amplification stratifies neuroblastoma into low-risk and high-risk. We aimed to establish whether a microRNA (miRNA) signature could be associated with prognosis in both groups. METHODS: Microarray expression profiling of human miRNAs and quantitative reverse-transcriptase PCR of selected miRNAs were performed on a preliminary cohort of 13 patients. Results were validated on an independent cohort of 214 patients. The relationship between miRNA expression and the overall or disease free survival was analysed on the total cohort of 227 patients using the log-rank test and the multivariable Cox proportional hazard model. RESULTS: A total of 15 of 17 miRNAs that discriminated high-risk from low-risk neuroblastoma belonged to the imprinted human 14q32.31 miRNA cluster and two, miR-487b and miR-410, were significantly downregulated in the high-risk group. Multivariable analyses showed miR-487b expression as associated with overall survival and disease-free survival in the whole cohort, independently of clinical covariates. Moreover, miR-487b and miR-410 expression was significantly associated with disease-free survival of the non-MYCN-amplified favourable neuroblastoma: localised (stage 1, 2 and 3) and stage 4 of infant <18 months. CONCLUSION: Expression of miR-487b and miR-410 shows predictive value beyond the classical high-/low-risk stratification and is a biomarker of relapse in favourable neuroblastoma. PMID- 21970885 TI - A difficult airway course. PMID- 21970884 TI - Risk factors for short- and long-term complications after groin surgery in vulvar cancer. AB - BACKGROUND: The cornerstone of treatment in early-stage squamous cell carcinoma (SCC) of the vulva is surgery, predominantly consisting of wide local excision with elective uni- or bi-lateral inguinofemoral lymphadenectomy. This strategy is associated with a good prognosis, but also with impressive treatment-related morbidity. The aim of this study was to determine risk factors for the short-term (wound breakdown, infection and lymphocele) and long-term (lymphoedema and cellulitis/erysipelas) complications after groin surgery as part of the treatment of vulvar SCC. METHODS: Between January 1988 and June 2009, 164 consecutive patients underwent an inguinofemoral lymphadenectomy as part of their surgical treatment for vulvar SCC at the Department of Gynaecologic Oncology at the Radboud University Nijmegen Medical Centre. The clinical and histopathological data were retrospectively analysed. RESULTS: Multivariate analysis showed that older age, diabetes, 'en bloc' surgery and higher drain production on the last day of drain in situ gave a higher risk of developing short-term complications. Younger age and lymphocele gave higher risk of developing long-term complications. Higher number of lymph nodes dissected seems to protect against developing any long-term complications. CONCLUSION: Our analysis shows that patient characteristics, extension of surgery and postoperative management influence short- and/or long-term complications after inguinofemoral lymphadenectomy in vulvar SCC patients. Further research of postoperative management is necessary to analyse possibilities to decrease the complication rate of inguinofemoral lymphadenectomy; although the sentinel lymph node procedure appears to be a promising technique, in 50% of the patients an inguinofemoral lymphadenectomy is still indicated. PMID- 21970886 TI - Continuous measurement of glucose: facts and challenges. PMID- 21970893 TI - Investigation of the valence electronic states of Ti(IV) in Ti silicalite-1 coupling X-ray emission spectroscopy and density functional calculations. AB - We present an application of valence to core X-ray emission spectroscopy to understand the electronic structure of the industrially relevant catalyst titanium silicalite-1. The experimental spectrum was modelled within density functional theory, adopting a one electron approach, investigating the effects of different basis sets, density functionals and cluster sizes. The description of titanium silicalite-1 valence states follows the Kohn-Sham evaluation of the molecular orbitals involved in the computed transitions. PMID- 21970887 TI - First-line therapy with coagulation factor concentrates combined with point-of care coagulation testing is associated with decreased allogeneic blood transfusion in cardiovascular surgery: a retrospective, single-center cohort study. AB - INTRODUCTION: Blood transfusion is associated with increased morbidity and mortality. We developed and implemented an algorithm for coagulation management in cardiovascular surgery based on first-line administration of coagulation factor concentrates combined with point-of-care thromboelastometry/impedance aggregometry. METHODS: In a retrospective cohort study including 3,865 patients, we analyzed the incidence of intraoperative allogeneic blood transfusions (primary endpoints) before and after algorithm implementation. RESULTS: Following algorithm implementation, the incidence of any allogeneic blood transfusion (52.5 vs. 42.2%; P < 0.0001), packed red blood cells (49.7 vs. 40.4%; P < 0.0001), and fresh frozen plasma (19.4 vs. 1.1%; P < 0.0001) decreased, whereas platelet transfusion increased (10.1 vs. 13.0%; P = 0.0041). Yearly transfusion of packed red blood cells (3,276 vs. 2,959 units; P < 0.0001) and fresh frozen plasma (1986 vs. 102 units; P < 0.0001) decreased, as did the median number of packed red blood cells and fresh frozen plasma per patient. The incidence of fibrinogen concentrate (3.73 vs. 10.01%; P < 0.0001) and prothrombin complex concentrate administration (4.42 vs. 8.9%; P < 0.0001) increased, as did their amount administered per year (179 vs. 702 g; P = 0.0008 and 162 * 103 U vs. 388 * 103 U; P = 0.0184, respectively). Despite a switch from aprotinin to tranexamic acid, an increase in use of dual antiplatelet therapy (2.7 vs. 13.7%; P < 0.0001), patients' age, proportion of females, emergency cases, and more complex surgery, the incidence of massive transfusion [(>=10 units packed red blood cells), (2.5 vs. 1.26%; P = 0.0057)] and unplanned reexploration (4.19 vs. 2.24%; P = 0.0007) decreased. Composite thrombotic/thromboembolic events (3.19 vs. 1.77%; P = 0.0115) decreased, but in-hospital mortality did not change (5.24 vs. 5.22%; P = 0.98). CONCLUSIONS: First-line administration of coagulation factor concentrates combined with point-of-care testing was associated with decreased incidence of blood transfusion and thrombotic/thromboembolic events. PMID- 21970894 TI - A perspective on nonresonant and resonant electronic response theory for time dependent molecular properties. AB - The development of electronic response theory in quantum chemistry has been reviewed, starting from the early 1970's and reaching the current state-of-the art. The general theory has been applied to the calculation of a large number of spectroscopic parameters over the years, and it has been implemented for the majority of standard electronic structure methods. Two formulations of response theory, the Ehrenfest expectation value and the quasi-energy derivative formulation, have turned into leading alternatives for the derivation of computationally tractable expressions of response functions, and they are here reviewed with an attempt to, as far as possible, leave out technical details. A set of four steps are identified as common in derivations of response functions, and the two formulations are compared along this series of steps. Particular emphasis is given to the situation when the oscillation of the weak external electromagnetic field is in resonance with a transition frequency of the system. The formation of physically sound response functions in resonance regions of the spectrum is discussed in light of the causality condition and the Kramers-Kronig relations, and it is achieved in wave function theory by means of the introduction of relaxation parameters in a manner that mimics what one sees in density matrix theory. As a working example, equations are illustrated by their application to a two-state model for para-nitroaniline including the ground and the lowest charge-transfer state in the electric dipole approximation. PMID- 21970895 TI - Carbon dioxide reduction by mononuclear ruthenium polypyridyl complexes. AB - New mononuclear ruthenium complexes with general formula [Ru(bid)(B)(Cl)] (bid is (1Z,3Z)-1,3-bis(pyridin-2-ylmethylene)isoindolin-2-ide; B = bidentate ligand 2,2' bipyridine or R(2)-bpy, where R = COOEt or OMe) were synthesized and tested as precatalysts for the hydrogenative reduction of CO(2) in 2,2,2-trifluoroethanol (TFE) as solvent with added NEt(3). Significant amounts of formic acid were produced by these catalysts and a kinetic analysis based on initial rate constants was carried out. The potential mechanisms including intermediate species for these catalytic systems were investigated by means of quantum chemical calculations to gain deeper insight into the processes. The effect of electron-donating and electron-withdrawing groups on catalyst performance was studied both experimentally and theoretically. PMID- 21970896 TI - The near disappearance of genital warts in young women 4 years after commencing a national human papillomavirus (HPV) vaccination programme. AB - BACKGROUND: Australia provided free quadrivalent human papillomavirus vaccines to 12-18-year-old girls and women aged <=26 years from mid-2007 until the end of 2009. After this time, only girls aged 12-13 years had access to free vaccines. METHODS: Before and after the study, of the proportion of new patients attending Melbourne Sexual Health Centre from mid-2004 to mid-2011, diagnosed with genital warts (GW) by risk group. RESULTS: From July 2004 to June 2011, 52 454 new patients were seen at Melbourne Sexual Health Centre and 5021 (9.6%, 95% CI 9.3% to 9.8%) were diagnosed with GW. From July 2004 to June 2007, the proportions with GW either increased or did not change in all groups. Comparing the two 12 month periods of 2007/2008 and 2010/2011, GW declined in women under 21 years from 18.6% to 1.9% and in heterosexual men under 21 years from 22.9% to 2.9%. The ORs per year for diagnosis of GW adjusted for number of sexual partners from July 2007 until June 2011 in women and heterosexual men <21 years were 0.44 (95% CI 0.32 to 0.58) and 0.42 (95% CI 0.31 to 0.60), respectively. There was no significant change in GW in women >=30 years (OR 0.97, 95% CI 0.84 to 1.12), heterosexual men >=30 years (OR 0.97, 95% CI 0.89 to 1.06) or in homosexual men (OR 0.95, 95% CI 0.85 to 1.07). CONCLUSION: The dramatic decline and near disappearance of GW in women and men under 21 years of age, 4 years after commencing this programme, suggest that the basic reproductive rate has fallen below one. PMID- 21970898 TI - Ionic liquids form ideal solutions. AB - An understanding of the activity of a solute in solution is vital for utilising the full potential of a reactive species. In this work we determine the activity of metal salts in a variety of ionic liquids. Some solutions behave like classical non-polar solvents whereas other are practically ideal solutions up to 1 mol kg(-1) which allows standard redox potentials to be determined. PMID- 21970897 TI - Public health research systems in the European union. AB - BACKGROUND: Strengthening health research is an important objective for international health organisations, but there has been less attention to support for health research in Europe. We describe the public-health (population and organisational level) research systems in the 27 European Union countries. METHODS: We developed a typology for describing health research structures based on funding streams and strategies. We drew data from internet sources and asked country informants to review these for consistency and completeness. The structures were described as organograms and narratives in country profiles for each of the 27 EU member states. National public-health research structures included public and independent funding organisations, 'mixed' institutions (which receive funds, and both use and allocate them) and provider institutions. RESULTS: Most health research is funded through ministries of science or science councils (and sometimes foundations), while parliaments and regions may also contribute. National institutes of public health are usually funded by ministries of health. Many national research organisations both determine research programmes and undertake health research, but there is a move towards public health sciences within the universities, and a transition from internal grants to competitive funding. Of 27 national research strategies, 17 referred to health and 11 to public health themes. Although all countries had strategies for public health itself, we found little coherence in public-health research programmes. The European Commission has country contact points for both EU research and health programmes, but they do not coordinate with national health-research programmes. CONCLUSIONS: Public-health research is broadly distributed across programmes in EU countries. Better understanding of research structures, programmes and results would improve recognition for public health in Europe, and contribute to practice. EU ministries of health should give greater attention to national public-health research strategies and programmes, and the European Union and the World Health Organisation can provide coordination and support. PMID- 21970899 TI - Fast multi-orbital equation of motion impurity solver for dynamical mean field theory. AB - We propose a fast multi-orbital impurity solver for dynamical mean field theory (DMFT). Our DMFT solver is based on the equations of motion (EOMs) for local Green's functions and is constructed by generalizing from the single-orbital case to the multi-orbital case with the inclusion of the inter-orbital hybridizations and applying a mean field approximation to the inter-orbital Coulomb interactions. The two-orbital Hubbard model is studied using this impurity solver within a large range of parameters. The Mott metal-insulator transition and the quasiparticle peak are well described. A comparison of the EOM method with the quantum Monte Carlo method is made for the two-orbital Hubbard model and good agreement is obtained. The developed method hence holds promise as a fast DMFT impurity solver in studies of strongly correlated systems. PMID- 21970900 TI - Comparison of choroidal and retinal endothelial cells: characteristics and response to VEGF isoforms and anti-VEGF treatments. AB - Neovascular eye diseases such as wet age-related macular degeneration and proliferative diabetic retinopathy are two of the most common causes of irreversible visual loss. Although mediated by vascular endothelial growth factor (VEGF), the mechanisms of these diseases are not fully understood. Molecular inhibitors of VEGF including pegaptanib, ranibizumab and bevacizumab are used as treatments for these diseases. However, there have been very few direct comparisons between these agents, and as dose and treatment regimes differ their relative efficacies are hard to determine. In vitro comparisons tend to use cells from different sites or species, which show heterogeneity in their responses. The aim of this study was to compare the characteristics of primary cultures of isolated human choroidal endothelial cells (hCEC) and retinal endothelial cells (hREC), and their proliferation responses to stimulation with VEGF 121 and 165, and to compare the anti-proliferative effects of these three drugs. hCEC and hREC were positive for the cell markers VEGFR1, VEGFR2, CD31, CD34 and von Willebrand's factor (vWF), with greater expression of CD34 on the hREC compared to hCEC. Contrary to previous assumptions VEGF isoforms 121 and 165 were found to be equally potent in stimulating endothelial cell proliferation. However, hREC exhibited higher proliferation with either VEGF isoform compared to hCEC. The anti-VEGF treatments ranibizumab and bevacizumab were effective in decreasing proliferation of hCEC induced by the two VEGF isoforms, individually and in combination, with ranibizumab being moderately more effective, particularly in hREC. Pegaptanib was effective in controlling the proliferation of hCEC stimulated by VEGF 165, but was ineffective against the stimulatory effect of VEGF 121. There were found to be significant differences in microvascular endothelial cells from the retina and choroid, both in the expression of cell markers and their behaviour in response to growth factors and currently available anti-VEGF agents, highlighting the importance of targeting treatments to specific intraocular vascular beds and/or diseases. PMID- 21970903 TI - An overview of osteoporosis: from genetics to clinics. AB - Osteoporosis is the most frequent metabolic bone disease and the one which mostly benefited from the knowledge of bone metabolism, both in terms of diagnosis and therapy. In the future, pharmacogenomics will optimize therapy response by customization on the basis of genotype, improving efficacy, and limiting the onset of side effects. PMID- 21970901 TI - Interaction between mechanical and osmotic forces in the isolated rabbit lens. AB - Based on our previous work showing that cow and rabbit lenses isolated with their accommodation anatomical components intact change volume during simulated accommodation in vitro, and that hyposmolality and hyperosmolality also produce volume changes, we tested the idea that exerting these forces simultaneously may add or counteract each other. Further, we attempted to find a point at which osmotic and mechanical forces may cancel each other. Using previously described methodology, we found that combined stretching and anisotonic conditions applied to a lens always produced less of a volume change than that observed on its paired lens from the fellow eye that was only subjected to anisotonic conditions. Our results suggest that a stretching force that increases the equatorial diameter by 0.4% and reduces the lens volume by 1.8% could be canceled by a hyposmotic force of about -20 to -30 mOsM. Counter-intuitively, lenses that were subjected to stretching and hyperosmolality had less volume decrease than their paired lenses only exposed to hypertonicity. This latter observation is likely due to the prevention by the mechanical stretching forces of the shortening of the equatorial diameter, which normally occurs in hypertonic media. PMID- 21970904 TI - Severe osteoporosis and its identification. AB - The severity of osteoporosis depends not only on densitometric data but implies the occurrence of at least one of the following conditions: increased risk of mortality, worsening of quality of life and significant disability in the performance of activities of daily living, presence of comorbidities that increase the risk of falls, the presence of at least one fragility fracture. PMID- 21970905 TI - Development of knowledge about osteoporosis in the world of orthopedics and traumatology. AB - The development of Orthopedics and Traumatology in the last 50 years have been characterized by the concurrence of several milestone events, such as the disappearance of polio and osteoarticular tuberculosis, the progress of some disciplines such as Anesthesia and Intensive Care, Diagnostic Imaging and technology development. As for other common diseases, also for osteoporosis the evolution of knowledge about pathophysiology and treatment represents a "must" to know for the orthopaedic surgeons. PMID- 21970906 TI - Biomechanical pathogenesis of fragility fractures in vertebrae and femur. AB - The causes of fragility fractures in vertebrae and femur are reviewed, and the possibility of both surgical and pharmacological treatment to prevent their occurrence is indicated. PMID- 21970907 TI - Report of GOST activities for the year 2009 and projects for the biennium 2010 2011. PMID- 21970908 TI - Clinical Governance: myth, hurdle, or new opportunity? AB - The goal of this paper is to outline the pragmatic use of the Clinical Governance and the urge to introduce it in daily practice. The present and future of modern medicine should be based on these principles. The reengineering of the Italian health care system has been mentioned as an example that took place in the early 90s. PMID- 21970909 TI - Clinical and forensic medicine issues in osteoporosis fractures. AB - Severe osteoporosis is characterized by a densitometry T-score lower than 2.5 associated with one or more fragility fractures. Fragility fractures represent a serious social and economic problem; the diagnosis of osteoporosis is an unachieved target by orthopaedic surgeons, despite the chance to detect it in many clinical assets and the availability of effective treatment tools. It is necessary to stick to scientific society guidelines, thus avoiding legal consequences related to the diagnosis, the therapy, the prescription coherence and the correct information due to patients. PMID- 21970910 TI - Prevention of falls and role of calcium and vitamin D. AB - Falls in the elderly are very common and represent a serious cause of morbidity, severe disability and death. Impairments of the mechanisms of postural stability with age and the presence of acute and chronic diseases may favour the occurrence of falls in the elderly. Together with the adoption of non-pharmacological measures, supplementation of calcium and vitamin D demonstrated to reduce hip fracture risk, particularly in institutionalized people. PMID- 21970911 TI - Secondary prevention of fractures and compliance to treatment in osteoporosis. AB - Osteoporosis is a mechanical incompetence of bone which finally leads to fracture. The occurrence of a fracture for a minor trauma is the definitive evidence of bone fragility and an indication of an higher probability for other fractures. Fracture at any site is a strong risk factor for a subsequent fracture, therefore any patient with a prevalent fracture is an ideal candidate for treatment due to the high risk for recurrence and to a favourable cost benefit ratio. Most of the available pharmacological agents approved for osteoporosis treatment are effective in reducing fracture risk in this class of patients. Unfortunately, poor compliance is very common in patients treated for osteoporosis and this leads to reduced benefits and ineffectual costs. Dose regimen simplification is neither the only nor the most important solution to improve compliance, and a multifaceted strategy targeting cognitive, behavioural and emotional factors should be employed. PMID- 21970912 TI - Role of the orthopaedic in fragility fracture and in the prevention of a new fracture: SIOT 2009 recommendations. AB - The progressive aging of the population inevitably leads to an increase in all age-related diseases, with osteoporosis arising as a health and social priority. Fragility fractures, resulting by Osteoporosis, may have important consequences such as hospitalizations with long periods of immobility, need of surgery, increased risk of disability and partial or complete loss of autonomy in the ordinary activities of daily life and related economical burden. It is therefore essential to implement immediately a tertiary prevention to reduce the risk of further fractures through a diagnostic-therapeutic evidence-based pathway. So, starting from the fracture, the orthopaedic surgeon is meant to play an essential role in the management of osteoporotic patients, both to reduce the risk of further fractures and improve long-term outcome in these people, thus lowering the health and life quality downward spiral that often results in fractures in the elderly. PMID- 21970913 TI - Inhibition of RANK ligand: a new option for preventing fragility fractures. AB - Cortical and trabecular bone undergo a continuous and balanced remodeling process, consisting of an osteoclast-mediated bone-resorption phase and an osteoblast- mediated bone-formation phase. An imbalance in this process, which favours bone resorption, results in bone loss and in damage to the skeletal microarchitecture. A new targeted anti-resorptive approach is represented by the inhibition of RANK ligand (RANKL), which is one of the primary mediators of osteoclast activity, essential for osteoclast formation, function and survival. PMID- 21970914 TI - New insights into the role of teriparatide. AB - Parathyroid hormone (PTH) is secreted by the parathyroid glands and is an important regulator of blood calcium concentrations. Synthesis and secretion of PTH are stimulated by a decrease in blood calcium. PTH has three actions: 1) to increase the release of calcium from bone, 2) to reduce renal clearance of calcium, and 3) to stimulate the production of 1,25 (OH)2D3. Human parathyroid hormone is a single chain polypeptide with 84 amino acids and a molecular weight of 9425 Da. The N-terminal region, 1-34, is biologically active and sufficient for regulation of mineral ion homeostasis (1). Recombinant teriparatide {human PTH(1-34) [hPTH (1-34)]}, currently the only bone-forming osteoporosis drug available for clinical use, increases bone turnover with a greater stimulation of formation than resorption (2). Bone turnover markers also rise during treatment with teriparatide (TPTD), with markers of bone formation rising early and rapidly, followed by rises in bone resorption markers. PMID- 21970915 TI - Periprosthetic femoral fractures: risk factors and current options to treatment. AB - The incidence and complexity of the femoral fracture around a previously implanted prosthetic component has been increasing over the last ten years, and treatment can be complex, expensive and associated with an increased risk of local and systemic complications. The surgical treatment options for periprosthetic fractures include open reduction and internal fixation of bone or revision arthroplasty. This review focuses on the current surgical techniques and the pharmacological therapy to provide biological support for the enhancement of bone healing. PMID- 21970916 TI - The possible introduction of anti-osteoporosis drugs as an integrated treatment in total hip arthroplasty. AB - The anchorage of cementless total hip arthroplasty relies on a direct bone to implant bonding. Several factors including material properties and surface treatment determine the interfacial response of the host bone to a foreign material. Another factor that must be taken into account is the bone remodeling after the prosthesis introduction. Considering this bone remodeling, in the last few years the possibility of using anti-osteoporotic drugs has been introduced as a supplementary and integrated treatment in total hip replacement. PMID- 21970917 TI - The use of anti-osteoporosis drugs in total knee arthroplasty. AB - Stress shielding, osteolysis, lack of integration affect the clinical results of total joint arthroplasty. Drugs as bisphosphonates administered after surgery may improve the fixation of the components to the bone, preserving the survival of the implant: however, few reports regarding applications in Total Knee Arthroplasty (TKA) are published. PMID- 21970918 TI - Prosthetic surgery in fragility osteopathy. AB - Elderly osteoporotic patients with a femoral neck fractures should undergo hip prosthesis replacement. Nevertheless, there is still debate about the best choice of treatment (Total Hip Replacement (THR) vs HemiArthroplasty (HA)). The aim of our study is to compare functional results of new polycarbonate- urethane (PCU) cup coupled with large diameter femoral head THR and bipolar HA. To verify our hypothesis, a consecutive series of 60 patients were randomized either to receive a bipolar HA or a THR. No statistically significant difference was found between the two groups in terms of age, surgical time and blood loss. Splitting the Harris Hip Score into two categories, pain and function, a trend for a better functional score was found in THR either at 3 and 12 months when compared to HA. Our study suggests that the use of a PCU acetabular cup with large diameter femoral head is an effective solution for osteoporotic patient and may provide a better hip function to this patient population. These positive results should be confirmed at a longer follow-up in a large cohort of patients. PMID- 21970919 TI - The evolution of vertebral fractures after surgical stabilization treatment. AB - In vertebral fractures, the size of the reductions in the anterior height and the deformity of the body are directly correlated to the intensity of the pain. Among the various therapeutic options, mini-invasive stabilization has been shown to obtain effective antalgic results in the short term, allowing a reduction in hospitalization time, the use of a corset, the employment of analgesic drugs and improvement of quality of life. Clinical improvement can be consequent to re balancing the biomechanics and the physiological resistance of the vertebrae. PMID- 21970920 TI - Case studies of kyphoplasty and vertebroplasty integrated by anti-osteoporotic therapy. AB - In severe osteoporosis with recent vertebral compression fracture, drug treatment with anabolic agent in the first 18 months can stimulate the healing process and reduce the rate of progression, preventing new fractures and improving the quality of life of the patient. The sequential therapy with bisphosphonates for at least another 12 months can help to maintain balanced bone turnover markers without the incidence of new fractures. The association of kyphoplasty or vertebroplasty and anti-osteoporotic drugs can be limited by national rules of eligibility. Hence the need for shared treatment protocols. PMID- 21970921 TI - Criticality of kyphoplasty and vertebroplasty. AB - Kyphoplasty and vertebroplasty are minimally invasive techniques to treat vertebral compression fractures, now considered as implying relative risks and being equally effective. A few considerations must anyway be made due to some unresolved problems. PMID- 21970922 TI - The role of physical forces in the management of bone and cartilage diseases and bone consolidation. AB - The international literature shows how the good results expected by the orthopaedic community and by patients themselves can only be achieved through a complete knowledge of the mechanism of action of physical forces in the management of bone tissue and cartilage, and through knowledge of the clinical indications and modality of treatment. PMID- 21970923 TI - Algorithm for employing physical forces in metabolic bone diseases. AB - Metabolic bone diseases, especially osteoporosis, demand a multidisciplinary approach. The physical forces find a rationale in the treatment of local alterations in bone-cartilage metabolism. In integrated treatment of vertebral fractures caused by fragility, stimulation with electrical fields has been observed to be effective in reducing pain and improving patients' quality of life. PMID- 21970924 TI - Osteosynthesis of fragility fractures. AB - The deepening knowledge about bone pathophysiology, together with the development of less invasive bone implants, fitted for the treatment of fragility fractures, the continuous advances in the creation of osteoconductive and osteoinductive biomaterials, the availability of bone active agents, capable of modulating fracture healing, actually represent the orthopaedic "weapons" to improve the surgical outcome and quality of life in patients with osteoporosis. PMID- 21970925 TI - Fragility fractures' osteosynthesis survey. AB - Surgical operations of fragility fractures are always more frequent, due to progressive population's aging. Proximal femoral fractures are the most frequent fractures in this surgical group. We cannot forget fractures on other districts: even if they are characterized by a lower death rate, they are equally important, especially as regards the outcome and the period of temporary disability. Fragility fractures' recovery is slower than a fracture in a healthy bone. To reduce these inconveniences, we should consider mini-invasive surgical procedures, which favour or simplify the recovery. The therapy against osteoporosis holds a top position to avoid new fractures, refractures, and assumes a bone's better quality in prosthesis. PMID- 21970926 TI - Problematic issues and conclusive remarks. AB - Since 2002, there has been a paradigm shift in the prevention and treatment of osteoporotic fractures. The focus now is on preventing fragility fractures and their associated complications rather than on treating low bone mineral density. Evidence shows that many patients with fractures do not undergo appropriate assessment or treatment. It is important to have an integrated approach in the overall patient management in order to address this care gap for high-risk patients. PMID- 21970927 TI - Bone healing and osteoporosis. AB - A correct fracture healing depends on the synergy between biomechanical, molecular and cellular factors. Focusing on different stages, fracture hematoma represents the starting point of the inflammatory process, with a critical role in triggering the process of fracture healing. The essential factors for bone repair are the activation of mesenchymal stem cells and the release of growth and regulatory factors. Moreover, the efficacy of fracture healing is determined by three ideal conditions: adequate blood supply, good contact between bone fragments and good stability. It is remarkable how the implant choice influences fracture healing after surgical treatment. In osteoporosis, bone quality adversely affects the tissue structural competence, increasing the risk of a complicated fracture healing. The qualitative and quantitative alterations established at the cellular level during osteoporosis explain the progressive deterioration of bone tissue healing ability. PMID- 21970928 TI - Biological and pharmacological factors influencing the fracture healing. AB - Many experimental data are available about the positive effect of some molecules on fracture repair, but data on their efficacy in the clinical use in humans are still lacking. Bone Morphogenetic Proteins are currently used in the treatment of delayed unions, but it is necessary to insert them surgically in the fracture site. The only pharmacological factor with clinical data is teriparatide, but more data are needed to confirm its effect on fracture healing in humans, even if experimental data in animals are robust. Data are also available on the effect on bone healing of other molecules used in osteoporosis treatments. Bisphosphonates favour the formation of a bigger callus, mechanically competent, but with a slow rate of remodelling. Estrogens and strontium ranelate have some experimental evidence of stimulating healing process. Robust experimental data are also available on an anti-Sost antibody. Anti-inflammatory drugs have a negative effect on bone healing, interfering with the early phases of inflammation. In conclusion more data, experimental and mainly clinical, are advocated to define whether it is possible to enhance bone healing, even if promising molecules, as teriparatide, are already available. PMID- 21970929 TI - Osteosynthesis systems in fragility fracture. AB - Atraumatic fractures, more commonly known as "fragility fractures", have as their basis the decreased bone strength due to osteoporosis. The major technical problem is the difficulty in obtaining secure fixation in osteoporotic bone, because the pull-out strength of implant is significantly reduced. The high rate of complications has encouraged extensive research into the development of implant which can improve the bone-implant interface by preventing high stress and distributing the forces transmitted to bone in a load-sharing, rather than load-bearing way. PMID- 21970930 TI - Acetabular fragility fractures in elderly patients. AB - The incidence of acetabular fractures in the elderly is recently becoming common. Acetabular fractures in this age range are more demanding, regarding fracture patterns, poor bone quality, patient status and potential comorbidities. Therefore it is necessary to determine the ideal treatment that should allow patients to obtain early mobilization and prevention of common complications. Different treatment options include conservative management, percutaneous minimally invasive procedures, open reduction and fixation (ORIF) and primary total hip arthroplasty (THA). The purpose of this paper is to review these options in fractured elderly patients. PMID- 21970931 TI - Biomaterials and bone. AB - The healing process of bone is influenced by several biochemical, biomechanics, cellular, hormonal and pathological mechanisms. The ideal biomaterials should therefore guarantee the same mechanisms and be able to "heal". At present we do not have such materials at our disposal. We can anyway select among several biomaterials with different characteristics to best suit our need. In this paper we will overview some of the biomaterials used today in bone surgery with regard to their main biological properties as well as their compatibility. PMID- 21970932 TI - Total hip arthroplasty and bone fragility. AB - The number of elderly people is steadily increasing: in the United States it will increase from 12.9% to 20% in 2030 with respect to the total population. Italy, with UK, Denmark and Sweden are the countries with the largest number of octogenarians (about 4% of the population) and it is estimated that this rate will increase by 300% over the next 50 years. The number of people affected by osteoarthritis will increase significantly and therefore the number of total hip arthroplasties will progressively increase. The success of an implant depends firstly by a flawless surgical technique, a correct and stable implant fixation and an optimal preoperative planning that should consider the bone quality of the patient, in order to choose a proper implant design. Different approaches could be followed to achieve adequate fixation: northern Europe surgeons prefer the cemented implant, instead American orthopedics generally use systems that allow a direct biological osteointegration. Elderly patients often present with multiple local and general problems that could affect significantly the normal course of a prosthetic surgery procedure and its results: they have bone tissue changes that lead to increased bone fragility and, consequently, difficulties to obtain primary stability. Osteoporotic bone is characterized by reduction of bone mass, decrease of cancellous bone trabeculae and by increased porosity of cortical bone. The bone fragility implies a greater risk of iatrogenic intraoperative fractures. Furthermore, difficulties linked to bone stock deficiencies become even more significant in revision surgery, where cortical bone thinning is associated with enlargement of the isthmus thus making more difficult to obtain distal fixation of prosthetic stems. At the moment, the role played by the drugs used for the treatment of osteoporosis during implant osteointegration is still not clearly understood and is still under investigation. PMID- 21970933 TI - Total knee arthroplasty in elderly osteoporotic patients. AB - Often in daily practice the choice of a prosthesis does not rise out of considerations about literature evidences, but it seems to be related to the personal experience and "surgical philosophy" of surgeon. The choice of prosthesis in total joint replacement is usually justified by biological and mechanical parameters that the surgeon considers before surgery. Osteoporosis is a disease characterized by a reduced bone mass and a degeneration of the bone tissue; it leads to bone fragility, so to a higher risk of fractures. Bone resistance, as all the changes in the microarchitecture of the bone tissue, is linked to bone density. Because of the bone density variation and/or the changes in the bone micro-architecture, as the bone strength decreases, the risk of fractures increases. It is important to understand all the factors taking part in both normal and abnormal bone remodelling. Osteoporosis does not imply a concrete bone loss, but a change of the bone micro-architecture itself. In these cases the choice of the patient and implant design are very important. In the period between March 1997-July 2002, we implanted 100 consecutive TKA (total knee arthroplasty) Genesis II in 97 subjects (79 female); mean age was 77.1 years old. All TKA were performed because of primary osteoarthritis of the knee. All patients had complete pain relief and excellent knee score. The surgical and medical complications were in accordance with the published literature. We must consider all existing medical conditions, the state of the knee and local needs of the elderly patient. Thus, within these limits, the total knee can improve the ability of patients to manage the activities of daily living and improve their quality of life. PMID- 21970934 TI - Long-term follow-up of 111 patients with angiotensin-converting enzyme inhibitor related angioedema. AB - OBJECTIVE: To investigate, for the first time, the frequency of recurrences of angiotensin-converting enzyme inhibitor (ACE-I)-related angioedema after the discontinuation of ACE-I. METHODS: This retrospective study was conducted in an outpatient tertiary-level centre for a total period of 173 months (about 14 years). Consecutive patients with recurrent angioedema symptoms, initiated during treatment with an ACE-I, who had been followed for at least 12 months after discontinuation of the drug were eligible. The primary study variable was the incidence of recurrences of angioedema after ACE-I discontinuation. Angioedema location, type of ACE-I and indication for this treatment and the drugs prescribed after the discontinuation of ACE-I were also evaluated. RESULTS: In total, 111 patients were followed; 54 of them (49%) were on enalapril. After discontinuation from ACE-I, 51 patients (46%) had further recurrences of angioedema; in 18 relapsers (16% of the total), the frequency of angioedema recurrences remained unchanged when compared with that reported during ACE-I treatment. The large majority of relapsers (88%) had the first recurrence of angioedema within the first month since ACE-I discontinuation. The switch to a different antihypertensive therapy did not seem associated with a reduction in the frequency of angioedema attacks. CONCLUSION: Even with all the limitations on any observational analysis, this long-term study suggests for the first time that patients with angioedema started while on ACE-I treatment seem to have a condition predisposing to angioedema that is elicited by the treatment with these drugs. Further studies in this field appear advocated due to the potential severity of angioedema attacks. PMID- 21970935 TI - Pathogenesis and management of hypertension after kidney transplantation. AB - Arterial hypertension is frequently encountered after renal transplantation and is associated not only with increased cardiovascular complications but also with decreased allograft survival. Adequate blood pressure control is, thus, as essential as immunologic surveillance for the long-term transplant care. Nevertheless, randomized control trials assessing treatment targets in these patients are not available and most of the evidence comes from studies in patients with native chronic kidney disease or the general population. In this regard, the renal transplant recipient is treated according to recommendations that are applicable to nontransplanted individuals at high cardiovascular risk. However, the accepted treatment targets for the nontransplanted population are recently being disputed and this makes the management of posttransplant hypertension even more challenging. PMID- 21970936 TI - Ability of different adiposity indicators to identify children with elevated blood pressure. AB - OBJECTIVE: Body composition measured by dual-energy X-ray absorptiometry (DXA) is believed to be superior to crude measures such as BMI or waist circumference (WC) to assess health risks associated with adiposity in adults. We compared the ability of BMI, WC, waist-to-height ratio (WHtR), percentage body fat from skinfold thickness, and measures of total and central fat assessed by DXA to identify children with elevated blood pressure (BP). STUDY DESIGN: The QUALITY Study follows 630 Caucasian families (father, mother, and child originally aged 8 10 years). BP, height, weight, WC, and skinfold thickness were measured according to standardized protocols. Elevated BP was defined as systolic or diastolic BP at least 90th age, sex, and height-specific percentile. Total and central fat were determined with DXA. The area under the receiver operating characteristic (ROC) curve (AUC) statistic was computed from logistic models that adjusted for age, sex, height, Tanner stage, and physical activity. RESULTS: All adiposity indicators were highly correlated. WC and WHtR did not show superior ability over BMI to identify children with elevated SBP (P = 0.421 and 0.473). Measures of total and central fat from DXA did not show an improved ability over BMI or WC to identify children with elevated SBP (P = 0.325-0.662). CONCLUSION: Results support the use of BMI in clinical and public health settings, at least in this age group. As all indicators had a limited ability to identify children with elevated BP, results also support measurement of BP in all children of this age independent of a weight status. PMID- 21970937 TI - Cardiac structure and function in relation to central blood pressure components in Chinese. AB - BACKGROUND: Data are limited with regard to the association of central blood pressure (BP) components with cardiac structure and function. METHODS: Our study was conducted in the framework of cardiovascular health examinations for the current and retired employees of a factory and their family members. We measured central BP by SphygmoCor and cardiac structure and function by echocardiography. RESULTS: The 826 participants (mean age 43.0 years) included 285 (34.5%) women and 184 (22.3%) hypertensive patients, of whom 78 (42.4%) took antihypertensive drugs. After adjustment for age, sex, body weight, body height, antihypertensive treatment, current smoking and alcohol intake, left atrial volume and left ventricular mass were significantly associated with brachial and central BP components (r = 0.09-0.21, P <= 0.01), whereas left ventricular diastolic dysfunction, evaluated by E/A ratio and deceleration time of E wave (DTE), was only significantly associated with brachial and central SBP (r = 0.14-0.18, P < 0.001). However, these correlation coefficients were quantitatively but nonsignificantly different between brachial and central BP (P >= 0.06). In regression models with similar adjustments, with 1-SD increase in central SBP (16.7 mmHg), E/A ratio significantly decreased by 5.5 +/- 1.2% and DTE significantly increased by 4.66 +/- 1.22 ms (P < 0.001). Sensitivity analyses in men and women separately and after exclusion of patients on antihypertensive medication were confirmatory. CONCLUSION: Cardiac structure was significantly and comparably associated with central BP components, but left ventricular diastolic dysfunction was only significantly associated with central SBP. PMID- 21970938 TI - Identifying coronary artery disease in men with type 2 diabetes: osteoprotegerin, pulse wave velocity, and other biomarkers of cardiovascular risk. AB - OBJECTIVES: In patients with type 2 diabetes, high serum levels of osteoprotegerin (OPG) have been associated with a greater risk of cardiovascular events. However, it remains unclear how well OPG performs when compared with traditional biomarkers of cardiovascular risk such as high-sensitivity C-reactive protein (hsCRP). Furthermore, OPG levels are also high in the presence of diabetes-related microvascular disease, and it is unclear whether OPG can distinguish microvascular disease from large-vessel atherosclerosis. The first aim of this study was to compare OPG levels against other biomarkers of cardiovascular risk in the identification of patients with documented multivessel coronary artery disease (CAD). The second aim was to compare OPG levels in patients with microvascular complications (microalbuminuria) against those with established CAD. METHODS: Three groups of male patients with type 2 diabetes were recruited: patients without microvascular complications or large-vessel atherosclerosis (n = 24), patients with microalbuminuria only (n = 23), and patients with microalbuminuria and documented multivessel CAD (n = 25). OPG, hsCRP, interleukin 6, urate, and pulse wave velocity were measured. RESULTS: Serum OPG levels were significantly higher in patients with a combination of microalbuminuria and CAD than in those with microalbuminuria alone. There were no significant differences in any of the other biomarkers between the groups. CONCLUSION: OPG was found to be superior to the other biomarkers studied in identifying patients with documented CAD. The presence of CAD was a greater determinant of serum OPG levels than microalbuminuria in our population. These findings support the use of OPG as a biomarker of cardiovascular risk. PMID- 21970939 TI - Metronomic breathing shows altered parasympathetic baroreflex function in untreated Fabry patients and baroreflex improvement after enzyme replacement therapy. AB - OBJECTIVE: In untreated Fabry patients without overt autonomic dysfunction and normal baroreflex sensitivity (BRS) at rest, BRS is impaired during orthostatic, sympathetic challenge but normalizes after enzyme-replacement therapy (ERT) (Hilz et al., J Hypertens 2010; 28:1438-1448). This study evaluated BRS during parasympathetic challenge with six cycles per minute metronomic deep breathing (MDB) in Fabry patients before and after ERT. METHODS: In 22 Fabry patients (28 +/- 8 years), we monitored RR-intervals (RRIs), SBP, and respiratory frequency during spontaneous breathing (spont_breath) and MDB, before and after 18 (11 patients) or 23 months (11 patients) of biweekly ERT (1.0 mg/kg agalsidase beta). We determined spectral powers of mainly sympathetic low-frequency (0.04-0.15 Hz) RRI fluctuations, parasympathetic high-frequency (0.15-0.5 Hz) RRI fluctuations, sympathetically mediated low-frequency powers of SBP and high-frequency powers of SBP. We calculated BRS (ms/mmHg) during spont_breath and MDB as low-frequency high-frequency alpha index (coherence >0.5). We compared parameters during spont_breath and MDB within and between patients before and after ERT and 15 age matched (27 +/- 5 years) healthy men (RANOVA and posthoc analysis; significance: P < 0.05). RESULTS: During spont_breath and MDB, parameters were similar between groups. Within the three groups, RRIs were lower, whereas RRI low-frequency powers and SBP low-frequency powers were higher during MDB than during spont_breath. BRS was similar during MBD and spont_breath in untreated patients (P > 0.05), but increased significantly with MDB in patients after ERT (P = 0.048) and in controls (P = 0.035). CONCLUSION: In untreated Fabry patients, MDB uncovers impaired BRS. After 18 or 23 months of ERT, MDB-induced BRS increase is similar in Fabry patients and controls, demonstrating that ERT not only restores sympathetic but also parasympathetic baroreflex activation. PMID- 21970940 TI - Stability of the Framingham Nutritional Risk Score and its component nutrients over 8 years: the Framingham Nutrition Studies. AB - BACKGROUND/OBJECTIVES: Diet quality indices are increasingly used in nutrition epidemiology as dietary exposures in relation to health outcomes. However, literature on the long-term stability of these indices is limited. We aimed to assess the stability of the validated Framingham Nutritional Risk Score (FNRS) and its component nutrients over 8 years, as well as the validity of the follow up FNRS. SUBJECTS/METHODS: Framingham Offspring/Spouse Study women and men (n=1734) aged 22-76 years were evaluated over 8 years. Individuals' nutrient intake and nutritional risk scores were assessed using 3-day dietary records administered at baseline (1984-1988) and at follow-up (1992-1996). Agreement between baseline and follow-up FNRS and nutrient intakes was evaluated by Bland Altman method; stability was assessed using intra-class correlation (ICC) and weighted Kappa statistics. The effect of diet quality (as assessed by the FNRS) on cardiometabolic risk factors was evaluated using analysis of covariance. RESULTS: Modest changes from baseline (?15%) were observed in nutrient intake. The stability coefficients for the FNRS (ICC: women, 0.49; men, 0.46; P<0.0001) and many nutrients (ICC ?0.3) were moderate. Over half of the women and men (58%) remained in the same or contiguous baseline and follow-up quartile of the FNRS and few (3-4%) shifted >1 quartile. The FNRS was directly associated with body mass index in women (P<0.01) and high-density lipoprotein cholesterol among both women (P<0.001) and men (P<0.01). CONCLUSIONS: The FNRS and its constituent nutrients remained relatively stable over 8 years of follow-up. The stability of diet quality has implications for prospective epidemiological investigations. PMID- 21970941 TI - A mathematical model for the hemoglobin response to iron intake, based on iron absorption measurements from habitually consumed Indian meals. AB - BACKGROUND/OBJECTIVES: The prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) is high in India and appear unchanging over decades. To understand the persistence of these disorders, it is critical to measure iron (Fe) absorption from cereal-based Indian meals, its modulation by ID and the time course of the response of hemoglobin (Hb) to Fe intake. SUBJESTS/METHODS: Fe absorption from rice-based meals was measured by the erythrocyte incorporation of the stable isotope label at 14 days in IDA (N=15) and Fe replete (IR) women (N=15). Hb level was used as surrogate for Fe status, and a response curve for Fe absorption versus the Hb level for a rice-based meal was constructed from measured data. This relationship was used as input for a mathematical model that examined the Hb response to different Fe intakes in normal and anemic women. RESULTS: The mean fractional Fe absorption from a rice-based meal in IR and IDA women was 2.7% and 8.3%, respectively. The model predicted that Fe intakes between 20 and 55 mg/day in low-bioavailability diets would result in stable, non anemic levels of Hb in women over a 1-year period. CONCLUSION: This mathematical model suggests that with a Fe intake of 20-30 mg/day and a dietary bioavailability of 3-5%, Hb concentration would hover around 12 g/dl with a variability of 0.5 g/dl in pre-menopausal adult women. PMID- 21970942 TI - Effect of breakfast glycemic index on metabolic responses during rest and exercise in overweight and non-overweight adolescent girls. AB - BACKGROUND/OBJECTIVES: The metabolic responses to mixed breakfast meals with different glycemic indexes (GI) and their effects on substrate metabolism during exercise in adolescent girls have not been examined. The interaction with weight status also warrants investigation. This study investigated the effect of mixed breakfast meals containing high GI (HGI) or low GI (LGI) carbohydrates on metabolic responses and fat oxidation during rest and exercise in overweight (OW) and non-overweight (NO) adolescent girls. SUBJECTS/METHODS: A total of 8 OW and 12 NO adolescent girls consumed an isoenergetic HGI (GI=73) or LGI (GI=44) breakfast 120 min before completing a 30-min treadmill walk at 50% ?[Vdot]O(2peak). RESULTS: Peak blood glucose concentration was higher for HGI compared with LGI in OW (P=0.023), but not NO (P>0.05) girls. Blood glucose total area under the curve (TAUC) was 13% higher in HGI compared with LGI in OW (P=0.006), but only 4% higher in NO (P=0.072) girls. Plasma insulin data were log(e) transformed (lninsulin). Plasma lninsulin concentrations were not different between HGI and LGI (P>0.05). Peak plasma lninsulin concentration (P=0.016) and TAUC (P=0.001) were greater in OW than NO girls. Fat oxidation during postprandial rest and exercise was not different between breakfasts (P>0.05). CONCLUSIONS: The elevated glycemic response in HGI compared with LGI was more pronounced in OW girls, suggesting a reduced ability to cope with the metabolic demands of the HGI, but not LGI, breakfast. Manipulation of breakfast GI did not alter fat oxidation during rest or subsequent moderate intensity exercise in OW and NO adolescent girls. PMID- 21970943 TI - Risk of metabolic syndrome in adults exposed to the great Chinese famine during the fetal life and early childhood. AB - BACKGROUND/OBJECTIVES: To determine whether exposure to the Chinese famine during fetal life and early childhood was associated with a greater risk of metabolic syndrome in later life. SUBJECTS/METHODS: We used data of adults from the 2008 annual physical examinations in Public Health Center of the First Affiliated Hospital of Chongqing Medical University in Chongqing. To minimize misclassification of the famine exposure periods, subjects born in 1959 and 1962 were excluded. Totally, 5040 participants were enrolled and categorized into control (1963-1964), fetally exposed (1960-1961) and postnatally exposed (1957 1958) group. We adopted the definition of metabolic syndrome recommended by the Chinese Diabetes Society in 2004. RESULTS: Women in fetally and postnatally exposed groups had significantly higher prevalences of metabolic syndrome than in control group (7.3% and 8.6% vs 4.0%, P<0.05, respectively). Women in fetally and postnatally exposed groups had a significantly higher risk of metabolic syndrome, as compared with control women (odds ratio (OR) 1.87 (95% confidence interval (CI) 1.15-3.04, P=0.012), OR 1.50 (95% CI 1.20-1.87, P=0.0003), respectively). Similar association was not observed among men. The prevalences of metabolic syndrome among men in control, fetally and postnatally exposed groups were 20.1%, 22.5% and 18.8%, respectively, but there was no significant difference of prevalences among the three groups. CONCLUSIONS: We found that exposure to the Chinese famine in early life period was associated with higher risk of metabolic syndrome in adulthood of women, but not men. This gender difference might be due to the mortality selection and son preference hypothesis. PMID- 21970944 TI - Vitamin D and K status influences bone mineral density and bone accrual in children and adolescents with celiac disease. AB - BACKGROUND/OBJECTIVES: Children with celiac disease (CD) are at risk for decreased bone mineral density (BMD) because of fat-soluble vitamin malabsorption, inflammation and/or under-nutrition. The study objective was to determine the interrelationships between vitamin K/D status and lifestyle variables on BMD in children and adolescents with CD at diagnosis and after 1 year on the gluten-free diet (GFD). SUBJECTS/METHODS: Children and adolescents aged 3-17 years with biopsy proven CD at diagnosis and after 1 year on the GFD were studied. BMD was measured using dual-energy X-ray absorptiometry. Relevant variables included: anthropometrics, vitamin D/K status, diet, physical activity and sunlight exposure. RESULTS: Whole-body and lumbar-spine BMD-z scores were low (< or = -1) at diagnosis (10-20%) and after 1 year (30-32%) in the children, independent of symptoms. Whole-body BMD-z scores (-0.55+/-0.7 versus 0.72+/-1.5) and serum levels of 25(OH) vitamin D (90.3+/-24.8 versus 70.5+/-19.8 nmol/l) were significantly lower in older children (>10 years) when compared with younger children (< or =10 years) (P<0.001). Forty-three percent had suboptimal vitamin D status (25(OH)-vitamin D <75 nmol/l) at diagnosis; resolving in nearly half after 1 year on the GFD. Twenty-five percent had suboptimal vitamin K status at diagnosis; all resolved after 1 year. CONCLUSIONS: Children and adolescents with CD are at risk for suboptimal bone health at time of diagnosis and after 1 year on GFD; likely due in part to suboptimal vitamin D/K status. Therapeutic strategies aimed at optimizing vitamin K/D intake may contribute to improved BMD in children with CD. PMID- 21970945 TI - Saharan dust and associations between particulate matter and daily mortality in Rome, Italy. AB - BACKGROUND: Outbreaks of Saharan-Sahel dust over Euro-Mediterranean areas frequently induce exceedances of the Europen Union's 24-hr standard of 50 MUg/m3 for particulate matter (PM) with aerodynamic diameter <= than 10 MUm (PM10). OBJECTIVES: We evaluated the effect of Saharan dust on the association between different PM fractions and daily mortality in Rome, Italy. METHODS: In a study of 80,423 adult residents who died in Rome between 2001 and 2004, we performed a time-series analysis to explore the effects of PM2.5, PM2.5-10, and PM10 on natural, cardiac, cerebrovascular, and respiratory mortality. We defined Saharan dust days by combining light detection and ranging (LIDAR) observations and analyses from operational models. We tested a Saharan dust-PM interaction term to evaluate the hypothesis that the effects of PM, especially coarse PM (PM2.5-10), on mortality would be enhanced on dust days. RESULTS: Interquartile range increases in PM2.5-10 (10.8 MUg/m3) and PM10 (19.8 MUg/m3) were associated with increased mortality due to natural, cardiac, cerebrovascular, and respiratory causes, with estimated effects ranging from 2.64% to 12.65% [95% confidence interval (CI), 1.18-25.42%] for the association between PM2.5-10 and respiratory mortality (0- to 5-day lag). Associations of PM2.5-10 with cardiac mortality were stronger on Saharan dust days (9.73%; 95% CI, 4.25-15.49%) than on dust-free days (0.86%; 95% CI, -2.47% to 4.31%; p = 0.005). Saharan dust days also modified associations between PM10 and cardiac mortality (9.55% increase; 95% CI, 3.81 15.61%; vs. dust-free days: 2.09%; 95% CI, -0.76% to 5.02%; p = 0.02). CONCLUSIONS: We found evidence of effects of PM2.5-10 and PM10 on natural and cause-specific mortality, with stronger estimated effects on cardiac mortality during Saharan dust outbreaks. Toxicological and biological effects of particles from desert sources need to be further investigated and taken into account in air quality standards. PMID- 21970946 TI - Homogenization with heat treatment: A cost effective alternative to nucleic acid extraction for herpes simplex virus real-time PCR from viral swabs. AB - Most laboratories use expensive commercial kits to purify nucleic acids and remove PCR inhibitors that may be present in clinical specimens. In this study a simple homogenization with heat treatment of herpes simplex virus types 1 and 2 (HSV-1/2) was shown to be equivalent to commercial kit-based nucleic acid extraction methods. With a cost of less than $1 USD per extraction, this method provides an economical, rapid, and effective method to recover HSV-1/2 DNA from swabs suitable for real-time HSV PCR. PMID- 21970947 TI - A quantitative collagen fibers orientation assessment using birefringence measurements: calibration and application to human osteons. AB - Even though mechanical properties depend strongly on the arrangement of collagen fibers in mineralized tissues, it is not yet well resolved. Only a few semi quantitative evaluations of the fiber arrangement in bone, like spectroscopic techniques or circularly polarized light microscopy methods are available. In this study the out-of-plane collagen arrangement angle was calibrated to the linear birefringence of a longitudinally fibered mineralized turkey leg tendon cut at variety of angles to the main axis. The calibration curve was applied to human cortical bone osteons to quantify the out-of-plane collagen fibers arrangement. The proposed calibration curve is normalized to sample thickness and wavelength of the probing light to enable a universally applicable quantitative assessment. This approach may improve our understanding of the fibrillar structure of bone and its implications on mechanical properties. PMID- 21970948 TI - An antiparallel actin dimer is associated with the endocytic pathway in mammalian cells. AB - The dynamic rearrangement of the actin cytoskeleton plays a key role in several cellular processes such as cell motility, endocytosis, RNA processing and chromatin organization. However, the supramolecular actin structures involved in the different processes remain largely unknown. One of the less studied forms of actin is the lower dimer (LD). This unconventional arrangement of two actin molecules in an antiparallel orientation can be detected by chemical crosslinking at the onset of polymerization in vitro. Moreover, evidence for a transient incorporation of LD into growing filaments and its ability to inhibit nucleation of F-actin filament assembly implicate that the LD pathway contributes to supramolecular actin patterning. However, a clear link from this actin species to a specific cellular function has not yet been established. We have developed an antibody that selectively binds to LD configurations in supramolecular actin structures assembled in vitro. This antibody allowed us to unveil the LD in different mammalian cells. In particular, we show an association of the antiparallel actin arrangement with the endocytic compartment at the cellular and ultrastructural level. Taken together, our results strongly support a functional role of LD in the patterning of supramolecular actin assemblies in mammalian cells. PMID- 21970949 TI - Two adjacent mutations on chromosome 16 discovered in a patient presenting with generalized convulsions after influenza A virus infection. AB - A 49-year-old otherwise healthy man was admitted to our hospital because of repeated generalized convulsions after influenza A virus infection. His family history was notable for consanguinity of parents. Initial laboratory tests revealed metabolic alkalosis with hypomagnesemia, as well as an elevated high density lipoprotein cholesterol level. He was diagnosed with Gitelman's syndrome and cholesteryl ester transfer protein deficiency by identifying homozygous mutations of causative genes, SLC12A3 and CETP, respectively. These two genes are located in the vicinity on chromosome 16, suggesting the possibility of autozygosity. This is the first case report highlighting the co-existence of these genetic disorders. PMID- 21970950 TI - Therapeutic efficacy of bevacizumab for age-related macular degeneration: what are the implications of CATT for routine management? AB - CATT (Comparison of Age-related macular degeneration [AMD] Treatment Trials) examined the efficacy of ranibizumab and bevacizumab for the treatment of neovascular AMD. This prospective, randomized, but unblinded trial revealed a significant improvement in vision with both treatments in terms of visual acuity; importantly, patients with juxtafoveal choroidal neovascularization (CNV) and retinal pigment epithelial detachments were not excluded from the study. Monthly treatment with the drugs resulted in similar increases in visual acuity, although angiograms indicated that ranibizumab was superior in terms of reducing retinal fluid and leakage. As the study also differentiated between a fixed regimen and an as-needed (pro re nata [PRN]) dosing regimen, a larger sample size and Bonferroni statistical correction were necessary. The equivalence of the PRN dosing of bevacizumab to the monthly treatment could not be confirmed. Almost all of the frequent deviations from the protocol (referring to retreatment criteria: 25.7-28.5%) resulted in under-treatment. Since this applied to both drugs equally, under-treatment alone could not explain the larger loss of visual acuity observed in the bevacizumab PRN arm. The PRN regimen was generally associated with a larger lesion size after 12 months compared with the fixed treatment regimens. The investigators accepted the drawbacks of an incomplete masking to allow co-payment by Medicare. As assessments of drug trials are often politically motivated, the higher demands of a non-inferiority trial compared with a superiority design must be emphasized. A comparison of the per-protocol and last observation-carried-forward analysis has not yet been published; ongoing subgroup analysis might highlight the impact of different lesion characteristics. While CATT provided further evidence for the efficacy of bevacizumab treatment, differences in adverse events between the two treatments (e.g. a higher rate of serious adverse events with bevacizumab compared with ranibizumab) were reported; however, these still have to be analysed, with the larger sample sizes of previous ranibizumab studies needing to be taken into account. Preclinical studies imply some differences between the drugs in terms of their adverse event profiles. A possible increased risk of adverse events could not be ruled out by previous clinical case series and CATT because the sample sizes and the follow-up intervals were not adequate. The large discrepancy in the price of bevacizumab versus ranibizumab in the US means a cost-benefit analysis is warranted. A lack of quality-of-life data has prevented calculation of an appropriate bevacizumab price in the context of its performance in the ophthalmological setting. Thus, CATT suggests that a favourable visual acuity might be achieved by very frequent administration of bevacizumab in patients with neovascular AMD. Although there are certain safety caveats, increased focus on subgroup analyses and obtaining longer follow-up data are expected to yield additional information of clinical relevance. PMID- 21970951 TI - Early steps of follicular lymphoma pathogenesis. AB - Follicular lymphoma (FL) pathogenesis is a complex and fascinating multi-hit process, escalating along successive derailments of the distinctive molecular and cellular mechanisms paving B-cell differentiation and activation. This progressive subversion of B-cell receptor diversification mechanisms and B-cell homeostasis likely occurs during a protracted preclinical phase of asymptomatic growth, in which premalignant clones already disseminate and establish "niches" in secondary lymphoid organs. Following FL diagnosis, a parallel indolent behavior is observed in most patients, slowly progressing over a period of many years, to eventually generate a highly refractory (and in some case transform into an aggressive subtype of) lymphoma. Novel insights in human germinal center B-cell biology recently allowed a more comprehensive understanding of the various illegitimate events sequentially involved in the premalignant progression phases. In this review, we will discuss how these new data have modified our perception of early FL pathogenesis, the new questions and challenges it opened up, and how this knowledge could impact on innovative programs of early detection, follow-up, and patient management. PMID- 21970952 TI - "A rose is a rose is a rose," but CVID is Not CVID common variable immune deficiency (CVID), what do we know in 2011? AB - Common variable immune deficiency (CVID) is the commonest symptomatic primary immunodeficiency and represents a heterogenous collection of disorders resulting mostly in antibody deficiency and recurrent infections. However, autoimmunity, granulomatous inflammation and malignancy frequently occur as part of the syndrome. The etiology of the condition has been poorly understood although in recent years, significant progress has been made in elucidating genetic mechanisms that can result in a CVID phenotype. In parallel to this, advances in treatment of the condition have also resulted in improved survival and quality of life for patients. There still remains significant work to be done in improving our understanding of the disease. In addition, recognition of the condition remains poor with significant diagnostic delays and avoidable morbidity. In this article, we review CVID with a particular focus on the areas of improving diagnosis and classification, recent developments in understanding the underlying etiology and genetics; and current treatment and monitoring recommendations for patients. PMID- 21970953 TI - Role of activation-induced cytidine deaminase in inflammation-associated cancer development. AB - Human cancer is a genetic disease resulting from the stepwise accumulation of genetic alterations in various tumor-related genes. Normal mutation rates, however, cannot account for the abundant genetic changes accumulated in tumor cells, suggesting that certain molecular mechanisms underlie such a large number of genetic alterations. Activation-induced cytidine deaminase (AID), a nucleotide editing enzyme that triggers DNA alterations and double-strand DNA breaks in the immunoglobulin gene, has been identified in activated B lymphocytes. Recent studies revealed that AID-mediated genotoxic effects target not only immunoglobulin genes but also a variety of other genes in both B lymphocytes and non-lymphoid cells. Consistent with the finding that several transcription factors including nuclear factor-kappaB (NF-kappaB) mediate AID expression in B cells, proinflammatory cytokine stimulation of several types of gastrointestinal epithelial cells, such as gastric, colonic, hepatic, and biliary epithelium, induces aberrant AID expression through the NF-kappaB signaling pathway. In vivo studies revealed that constitutive AID expression promotes the tumorigenic pathway by enhancing the susceptibility to mutagenesis in a variety of epithelial organs. The activity of AID as a genome mutator provides a new avenue for studies aimed at understanding mutagenesis mechanisms during carcinogenesis. PMID- 21970954 TI - Comparative genomics and evolution of immunoglobulin-encoding loci in tetrapods. AB - The immunoglobulins (Igs or antibodies) as an integral part of the tetrapod adaptive immune response system have evolved toward producing highly diversified molecules that recognize a remarkably large number of different antigens. Antibodies and their respective encoding loci have been shaped by different and often contrasting evolutionary forces, some of which aim to conserve an established pattern or mechanism and others to generate alternative and diversified structural and functional configurations. The genomic organization, gene content, ratio between functional genes and pseudogenes, number and position of recombining genetic elements, and the different levels of divergence present at the germline of the Ig-encoding loci have been evolutionarily shaped and optimized in a lineage- and, in some cases, species-specific mode aiming to increase organismal fitness. Further, evolution favored the development of multiple mechanisms of primary and secondary antibody diversification, such as V(D)J recombination, class switch recombination, isotype exclusion, somatic hypermutation, and gene conversion. Diverse tetrapod species, based on their specific germline configurations, use these mechanisms in several different combinations to effectively generate a vast array of distinct antibody types and structures. This chapter summarizes our current knowledge on the Ig-encoding loci in tetrapods and discusses the different evolutionary mechanisms that shaped their diversification. PMID- 21970955 TI - Pax5: a master regulator of B cell development and leukemogenesis. AB - The B cell lineage of the hematopoietic system is responsible for the generation of high-affinity antibodies, which provide humoral immunity for protection against foreign pathogens. B cell commitment and development depend on many transcription factors including Pax5. Here, we review the different functions of Pax5 in regulating various aspects of B lymphopoiesis. At B cell commitment, Pax5 restricts the developmental potential of lymphoid progenitors to the B cell pathway by repressing B-lineage-inappropriate genes, while it simultaneously promotes B cell development by activating B-lymphoid-specific genes. Pax5 thereby controls gene transcription by recruiting chromatin-remodeling, histone modifying, and basal transcription factor complexes to its target genes. Moreover, Pax5 contributes to the diversity of the antibody repertoire by controlling V(H)-DJ(H) recombination by inducing contraction of the immunoglobulin heavy-chain locus in pro-B cells, which is likely mediated by PAIR elements in the 5' region of the V(H) gene cluster. Importantly, all mature B cell types depend on Pax5 for their differentiation and function. Pax5 thus controls the identity of B lymphocytes throughout B cell development. Consequently, conditional loss of Pax5 allows mature B cells from peripheral lymphoid organs to develop into functional T cells in the thymus via dedifferentiation to uncommitted progenitors in the bone marrow. Pax5 has also been implicated in human B cell malignancies because it can function as a haploinsufficient tumor suppressor or oncogenic translocation fusion protein in B cell precursor acute lymphoblastic leukemia. PMID- 21970956 TI - Development: Predictable looping of the developing vertebrate gut explained. PMID- 21970958 TI - Cancer: Tumors secrete gaseous sulfur-containing compounds. PMID- 21970959 TI - Hepatitis: Genetic variability in HBV resistance. PMID- 21970960 TI - Helicobacter pylori: 14-day triple therapy may be the optimal empirical therapy for Helicobacter pylori eradication in Latin American populations. PMID- 21970962 TI - Obesity: New light shed on obesity-associated gut microbiota. PMID- 21970963 TI - Motility: Magnetic stimulation of the cerebellum could restore swallowing. PMID- 21970964 TI - Endoscopy: ESD is associated with a moderate risk of deep vein thrombosis that may be determined by D-dimer levels. PMID- 21970965 TI - Liver transplantation: Toward a unified allocation system. PMID- 21970966 TI - Superior colliculus lesions impair threat responsiveness in infant capuchin monkeys. AB - The ability to react fast and efficiently in threatening situations is paramount for the survival of organisms and has been decisive in our evolutionary history. Defense mechanisms in primates rely on the fast recognition of potential predators and facial expressions of conspecifics. The neural circuitry responsible for the detection of threat is generally thought to be centered on the amygdala. Although it is a pivotal structure in the processing of emotional stimuli, the amygdala does not seem necessary for the early stages of this process. Here we show that bilateral neurotoxic lesions of the superior colliculus in infant capuchins monkeys impaired the recognition of a rubber-snake in a threat-reward conflict task. Lesioned monkeys were uninhibited by a snake in a food-reward retrieval task. Lack of inhibition in the task was observed over the course of 15 weeks. The long lasting recognition impairment of a natural predator observed here is similar to the tameness aspects of Kluver-Bucy syndrome, indicating an important role of this structure in threat recognition. PMID- 21970967 TI - Overexpression of GRP78 protects glial cells from endoplasmic reticulum stress. AB - Endoplasmic reticulum (ER) stress induces apoptotic cell death by causing the accumulation of structurally abnormal proteins. The 78-kDa glucose-regulated protein (GRP78) is an ER chaperone that regulates protein folding in the ER and has been suggested to contribute to cell survival. Using the rat C6 glioma cell line and flow cytometry, we assessed GRP78 expression following tunicamycin- and glutamate-induced ER stress. The results showed that GRP78 expression is upregulated following ER stress and has protective effects on injured glial cells. Annexin V and propidium iodide labeling revealed cells transiently expressing GRP78 prior to injury were protected against high-concentrations of tunicamycin and glutamate within 72 h. Our findings support the hypothesis that GRP78 inhibits cell death associated with ER stress. PMID- 21970968 TI - Effects of chronic social defeat stress on MAP kinase cascade. AB - Chronic psychological and social stress can cause psychiatric disorders in humans. In this study, we analyzed the mitogen-activated protein kinase (MAPK) cascade in the hippocampus of chronically socially defeated rats. The rats that were subjected to social defeat every day for 5 weeks showed physiological and behavioral changes, including a reduced rate of weight gain, enlarged adrenal glands, and increased immobility in the forced swim test without concomitant changes in locomotor activity in the open field test. Altered body weight and enlarged adrenal glands are typical symptoms of human depression. Prolonged immobility in the forced swim test indicates behavioral despair, a well established index of depression. Because the MAPK cascade plays a pivotal role in depression, we quantified the expression of these molecules in the hippocampus of chronically defeated rats using western blot analysis. We found that phospho-MAPK kinases 1/2 (MEK1/2) and phospho-extracellular signal-regulated kinases 1/2 (ERK1/2) were decreased, whereas MAPK phosphatase-1 (MKP-1) was increased in the hippocampus of chronically defeated rats compared to the control group. These results were consistent with findings in depressed patients and other animal models of depression. In conclusion, our findings suggest that chronic psychosocial stress in Wistar rats induced depression-like behavior and downregulated the MAPK cascade in the hippocampus. PMID- 21970969 TI - Effect of monolayer cells on sphere cells--two types of cells that emerge during the neural differentiation of mouse embryonic stem cells. AB - Embryonic stem (ES) cells represent a valuable resource for transplantation and tissue engineering applications. For derivation of neural cells, a five-stage differentiation protocol has been widely applied, which involves the propagation of ES cells, formation of embryoid bodies (EBs), selection of neural stem cells (NSCs), expansion of NSCs, and further maturation of NSCs to neurons. During the expansion stage (the fourth stage), two types of cells with distinct morphologies normally emerge, with one type being monolayer cells and the other sphere-like aggregates growing on top of the monolayer cells. In this study, we focus on how the monolayer cells may affect different aspects of aggregate cells, which may have important implications for regenerative medicine. We find that monolayer cells can support the proliferation and decrease the apoptosis rate of sphere cells, as well as facilitate the production of Tuj1-positive cells from sphere cells. In addition, transplantation of monolayer cells into nude mice does not result in tumor formation nor affects the tumorigenicity of sphere cells, when grafted together with monolayer cells. PMID- 21970970 TI - Finger force sharing during an adapted power grip task. AB - This study analyses the finger force sharing using power grip task with adapted experimental conditions. This paradigm limits as much as possible the external constraints when the Index (I), Middle (M), Ring (R) and Little (L) fingers act simultaneously: the thumb did not oppose the other fingers and no secondary moments were applied to the wrist. The motor control of these two parameters was limited in contrary to the previous paradigms of the literature. The results showed that the force sharing, the force deficit and the location of the neutral line were different in this condition compared to a classical finger pressing task. We suggest that the observed behaviour was due to the peripheral architecture (muscle bellies, multi-digit motor units) more than the control of the constraints of the tasks. We propose to use this paradigm in further fundamental studies and also during clinical programmes to evaluate the rehabilitation of peripheral architecture characteristics and also finger control. PMID- 21970971 TI - Breaches of the pial basement membrane are associated with defective dentate gyrus development in mouse models of congenital muscular dystrophies. AB - A subset of congenital muscular dystrophies (CMDs) has central nervous system manifestations. There are good mouse models for these CMDs that include POMGnT1 knockout, POMT2 knockout and Large(myd) mice with all exhibiting defects in dentate gyrus. It is not known how the abnormal dentate gyrus is formed during the development. In this study, we conducted a detailed morphological examination of the dentate gyrus in adult and newborn POMGnT1 knockout, POMT2 knockout, and Large(myd) mice by immunofluorescence staining and electron microscopic analyses. We observed that the pial basement membrane overlying the dentate gyrus was disrupted and there was ectopia of granule cell precursors through the breached pial basement membrane. Besides these, the knockout dentate gyrus exhibited reactive gliosis in these mouse models. Thus, breaches in the pial basement membrane are associated with defective dentate gyrus development in mouse models of congenital muscular dystrophies. PMID- 21970972 TI - Neuroprotective effect of silibinin in diabetic mice. AB - Diabetes mellitus is associated with a higher oxidative stress and reduced activity of the antioxidant defense system in different brain regions. Results from numerous studies reported impaired cognitive and neurochemical function in diabetic patients and streptozotocin induced diabetic rodents. It is well established that polyphenols exert potent antioxidant and protective functions. Based on recent findings, one potential target for the antioxidant/antinflammatory properties of polyphenols is the heme oxygenase (HO) 1 pathway. Among various compounds tested silibinin, the main component of silymarin, has been shown to possess a strong antioxidant effect in various experimental models; however a study on the possible neuroprotective effect of this compound on the brain of diabetic animals is currently lacking. Therefore, we studied and measured in lean mice (db/m) and knock out mice for the leptin receptors mice (db/db) the effect of silibinin on HO-1 protein levels, non proteic thiol groups, isoprostanes and 8-OH deoxyguanosine (markers of lipid peroxidation and DNA damage, respectively) in different brain regions. Our results showed that HO-1 is differently expressed in various brain regions in db/db mice when compared to lean animals. Furthermore, silibinin provides DNA protection and reduces oxidative stress in a brain specific area, in part via the activation of the HO system. Silibinin may provide a valid tool to counteract oxidative stress in the diabetic status in the central nervous system under diabetic condition. PMID- 21970973 TI - Impairment of conflict processing in alexithymic individuals. AB - Alexithymia is characterized by difficulties in identifying and describing feelings and in distinguishing between feelings and bodily sensations. Several researchers have examined the impairment of executive functioning in alexithymia; however, only a few studies have been specifically concerned with conflict processing in alexithymia. Utilizing the attention network test (ANT), we investigated whether alexithymia is related to or independent of executive function, especially with respect to conflict processing. Participants included 33 subjects with high alexithymia scores on the 20-item Toronto Alexithymia Scale (TAS-20) and 30 matched subjects with low alexithymia scores. On the ANT, we found a significant difference between the two groups in conflict processing, and no significant difference in alerting and orienting dimensions. These findings suggested that subjects with high alexithymia scores have selective impairment in conflict processing. PMID- 21970974 TI - Alterations in neuronal survival and glial reactions after axotomy by ceftriaxone and minocycline in the mouse hypoglossal nucleus. AB - Some antibiotics are suggested to exert neuroprotective effects via regulation of glial responses. Attenuation of microglial activation by minocycline prevents neuronal death in a variety of experimental models for neurological diseases, such as cerebral ischemia, Parkinson's and Huntington's disease. Ceftriaxone delays loss of neurons in genetic animal models of amyotrophic lateral sclerosis through upregulation of astrocytic glutamate transporter expression (GLT-1). However, it remains largely unknown whether these antibiotics are able to protect neurons in axotomy models for progressive motor neuron diseases. Recent studies have shown that the axotomized motoneurons of the adult rat can survive, whereas those of the adult mouse undergo neuronal degeneration. We thus examined the possible effects of ceftriaxone and minocycline on neuronal loss and glial reactions in the mouse hypoglossal nucleus after axotomy. The survival rate of lesioned motoneurons at 28 days after axotomy (D28) was significantly improved by ceftriaxone and minocycline treatment. There were no significant differences in the cellular densities of astrocytes between ceftriaxone-treated and saline treated animals. Ceftriaxone administration increased the expression of GLT-1 in the hypoglossal nucleus, while it suppressed the reactive increase of glial fibrillary acidic protein (GFAP) expression to control level. The cellular densities of microglia at D28 were significantly lower in minocycline-treated mice than in saline-treated mice. The time course analysis showed that immediate increase in microglia at D3 and D7 was not suppressed by minocycline. The present observations show that minocycline and ceftriaxone promote survival of lesioned motoneurons in the mouse hypoglossal nucleus, and also suggest that alterations in glial responses might be involved in neuroprotective actions of antibiotics. PMID- 21970975 TI - Alterations in the blood brain barrier in ageing cerebral cortex in relationship to Alzheimer-type pathology: a study in the MRC-CFAS population neuropathology cohort. AB - Impairment of the blood brain barrier (BBB) in human brain ageing and its relationship to Alzheimer-type pathology remains poorly defined. We have investigated the BBB in temporal cortex of brain donations from a population representative sample of 92 participants from the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS), a longitudinal study with a programme of brain donation. BBB alteration was investigated by immunohistochemistry to albumin and fibrinogen and to the tight junction proteins claudin-5, zonula occludens-1 (ZO-1) and occludin. BBB leakage showed wide population-variation and increased with progression of Alzheimer-type pathology, though with considerable overlap between different levels of Alzheimer-type pathology. This was accompanied by increased mean vascular density, but not by down-regulation of tight junction proteins. ZO-1 and occludin were also expressed in glia. Mechanisms leading to BBB leakage in brain ageing remain to be defined, but the population-variation in BBB changes and its early increase in relationship to Alzheimer-type pathology progression suggest that BBB dysfunction contributes to brain ageing. PMID- 21970976 TI - Comparison of yttrium-90 quantitative imaging by TOF and non-TOF PET in a phantom of liver selective internal radiotherapy. AB - The aim of this study is to determine the feasibility of achieving quantitative measurement in (90)Y-microspheres liver selective internal radiotherapy (SIRT) by imaging (90)Y with a conventional non-time of flight (TOF) PET device. Instead of the bremsstrahlung x-rays of the beta-decay, the low branch of e(-)- e(+) pair production in the (90)Y-decay was used. The activity distribution in a phantom simulated liver SIRT was obtained by direct (90)Y-PET imaging. We tested a LYSO TOF PET and two GSO and BGO non-TOF PET scanners using a 3.6-l cylindrical phantom filled with the (90)Y solution containing two sets of hot and cold spheres. The best hot contrast was obtained with the LYSO TOF. It was close to the expected value and remained constant, even for short acquisition times. The LYSO non-TOF was about 10% lower. The GSO performed similarly but degraded for shorter times whilst the BGO was the worst with 40% loss. For the cold spheres, the LYSO TOF and the GSO provided the best results, while the LYSO non-TOF and the BGO were the worst. (90)Y PET imaging in liver SIRT is achievable with LYSO TOF. Conventional LYSO and GSO show a loss of contrast and require longer acquisition times. BGO imaging is not feasible for dosimetry calculation. PMID- 21970978 TI - A novel tungsten trioxide (WO3)/ITO porous nanocomposite for enhanced photo catalytic water splitting. AB - Hybrid nanocomposite films of ITO-coated, self-assembled porous nanostructures of tungsten trioxide (WO(3)) were fabricated using electrochemical anodization and sputtering. The morphology and chemical nature of the porous nanostructures were studied by Scanning Electron Microscopy (SEM) and X-ray Photoelectron Spectroscopy (XPS), respectively. The photoelectrochemical (PEC) properties of WO(3) porous nanostructures were studied in various alkaline electrolytes and compared with those of titania nanotubes. A new type of alkaline electrolyte containing a mixture of NaOH and KOH was proposed for the first time to the best of our knowledge and shown to improve the photocurrent response of the photoanodes. Here, we show that both the WO(3) nanostructures and titania nanotubes (used for comparison) exhibit superior photocurrent response in the mixture of NaOH and KOH than in other alkaline electrolytes. The WO(3) porous nanostructures suffered from surface corrosion resulting in a huge reduction in the photocurrent density as a function of time in the alkaline electrolytes. However, with a protective coating of ITO (100 nm), the surface corrosion of WO(3) porous nanostructures reduced drastically. A tremendous increase in the photocurrent density of as much as 340% was observed after the ITO was applied to the WO(3) porous nanostructures. The results suggest that the hybrid ITO/WO(3) nanocomposites could be potentially coupled with titania nanotubes in a multi junction PEC cell to expand the light absorption capability in the solar spectrum for water splitting to generate hydrogen. PMID- 21970979 TI - Human immunodeficiency virus-1 Nef suppresses Hsp70-mediated Tat activation. AB - The human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) contains binding sites for several host transcription factors that contribute to HIV-1 gene expression. Although previous reports have indicated that HIV-1 Nef positively or negatively regulates HIV-1 gene expression, the precise molecular mechanisms by which this occurs remain largely unknown. In this study, we report that Nef suppressed LTR-driven transcription only in the presence of HIV-1 Tat, which was localized to the cytoplasm and degraded by the proteasome. However, the depletion of Hsp70 was found to reduce the suppressive effect of Nef on HIV-1 gene expression. These results suggest that Nef suppresses Hsp70-mediated HIV-1 Tat activation. PMID- 21970980 TI - Competition between Kondo and RKKY correlations in the presence of strong randomness. AB - We propose that competition between Kondo and magnetic correlations results in a novel universality class for heavy fermion quantum criticality in the presence of strong randomness. Starting from an Anderson lattice model with disorder, we derive an effective local field theory in the dynamical mean-field theory approximation, where randomness is introduced into both hybridization and Ruderman-Kittel-Kasuya-Yosida (RKKY) interactions. Performing the saddle-point analysis in the U(1) slave-boson representation, we reveal its phase diagram which shows a quantum phase transition from a spin liquid state to a local Fermi liquid phase. In contrast with the clean limit case of the Anderson lattice model, the effective hybridization given by holon condensation turns out to vanish, resulting from the zero mean value of the hybridization coupling constant. However, we show that the holon density becomes finite when the variance of the hybridization is sufficiently larger than that of the RKKY coupling, giving rise to the Kondo effect. On the other hand, when the variance of the hybridization becomes smaller than that of the RKKY coupling, the Kondo effect disappears, resulting in a fully symmetric paramagnetic state, adiabatically connected to the spin liquid state of the disordered Heisenberg model. We investigate the quantum critical point beyond the mean-field approximation. Introducing quantum corrections fully self-consistently in the non crossing approximation, we prove that the local charge susceptibility has exactly the same critical exponent as the local spin susceptibility, suggesting an enhanced symmetry at the local quantum critical point. This leads us to propose novel duality between the Kondo singlet phase and the critical local moment state beyond the Landau-Ginzburg-Wilson paradigm. The Landau-Ginzburg-Wilson forbidden duality serves the mechanism of electron fractionalization in critical impurity dynamics, where such fractionalized excitations are identified with topological excitations. PMID- 21970977 TI - Multiple genes in the 15q13-q14 chromosomal region are associated with schizophrenia. AB - OBJECTIVE: The chromosomal region, 15q13-q14, including the alpha7 nicotinic acetylcholine receptor gene, CHRNA7, is a replicated region for schizophrenia. This study fine-mapped genes at 15q13-q14 to determine whether the association is unique to CHRNA7. METHODS: Family-based and case-control association studies were performed on Caucasian-non-Hispanic and African-American individuals from 120 families as well as 468 individual patients with schizophrenia and 144 well characterized controls. Single-nucleotide polymorphism (SNP) markers were genotyped, and association analyses carried out for the outcomes of schizophrenia, smoking, and smoking in schizophrenia. RESULTS: Three genes were associated with schizophrenia in both ethnic populations: TRPM1, KLF13, and RYR3. Two SNPs in CHRNA7 were associated with schizophrenia in African-Americans, and a second SNP in CHRNA7 was significant for an association with smoking and smoking in schizophrenia in Caucasians. CONCLUSION: Results of these studies support association of the 15q13-q14 region with schizophrenia. The broad positive association suggests that more than one 15q gene may be contributing to the disorder, either in combination or through a regulatory mechanism. PMID- 21970981 TI - Integrated Oxygenator FX05. AB - In recent years, there has been a trend to incorporate arterial filters into cardiopulmonary bypass (CPB) oxygenators. The FX oxygenators are the first examples of integrating a filter around the fibers of the oxygenator. To assess the efficacy of the FX05 oxygenator, in comparison with our existing CPB setup (RX05 oxygenator + arterial filter), we randomly assigned 40 patients undergoing CPB, with calculated flows <1.5 L/min, to FX05 or RX05 + arterial filter (19 FX and 21 RX). Embolic load was assessed using the emboli detection and classification quantifier, with sensors placed prefilter and postfilter/oxygenator at identical distances for both devices. A total of 6,270 FX readings and 6,183 RX readings were obtained. Because of the extremely skewed nature of the data, the prefilter embolic volumes were divided into deciles, and each decile was analyzed separately. Our results show that the devices perform similarly; both filter out a high percentage of the prefilter embolic load. Our data support that in the clinical setting, the FX05 is as effective at removing emboli as the RX05 with an arterial filter (CXAF02) which, in conjunction with the prime volume reduction and circuit simplification, has warranted our conversion to the FX series of oxygenators. PMID- 21970982 TI - Use of minimal extracorporeal circulation circuit for left ventricular assist device implantation. AB - We describe successful use of a minimal extracorporeal circulation circuit (MECC) as an alternative to conventional cardiopulmonary bypass (CPB) for the implantation of left ventricular assist device (LVAD) in a 65-year-old patient with ischemic dilated cardiomyopathy. A Jarvik 2000 was implanted through a median sternotomy with the outflow graft anastomosed to the ascending aorta. MECC circuit provides optimal circulatory support throughout the procedure and prevents hemodynamic instability caused by marked displacement of the heart for exposure of the left ventricular apex, while minimizing the adverse effects of conventional CPB. PMID- 21970983 TI - Photolabile micropatterned surfaces for cell capture and release. AB - A method for capture and release of cells was developed using a photolabile linker and antibody-attached glass surface with a poly(ethylene glycol) (PEG) pattern. PMID- 21970984 TI - Longitudinal compression: a "new" complication with modern coronary stent platforms--time to think beyond deliverability? PMID- 21970985 TI - Chromatin organization, structure and dynamics. PMID- 21970987 TI - The linker histone H1C contributes to the SCA7 nuclear phenotype. AB - Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disease caused by a polyglutamine expansion in ataxin-7, a subunit of the SAGA coactivator, which leads to progressive neuronal dysfunction and cell death in cerebellum, brainstem and retina. Increased nuclear volume, chromatin decondensation and deregulated gene expression were reported in a SCA7 mouse model expressing mutant ataxin-7 in rod photoreceptors. We analyzed the SCA7-induced chromatin reorganization by immunogold labeling, stereology, electron tomography and showed that in SCA7 rods the most external heterochromatin ring, corresponding to facultative heterochromatin, becomes fragmented and decondensed. The amounts of acetylated histone H3 and H4 tails were found to be unchanged in nuclear extracts of SCA7 retinas and their cellular distribution appeared similar in wild-type and SCA7 mice in so far that in both cases acetylated histones are positioned at the interface between eu- and hetero-chromatin. We found that the amount of the linker histone H1c is strongly reduced in nuclear extracts of SCA7 retinas and that the cellular distribution of H1c is particularly altered in the facultative heterochromatin compartment. The decreased histone H1c content thus provides a coherent explanation for the chromatin decondensation observed in SCA7 rod photoreceptor nuclei. PMID- 21970986 TI - The nuclear envelope as a chromatin organizer. AB - In the past 15 years our perception of nuclear envelope function has evolved perhaps nearly as much as the nuclear envelope itself evolved in the last 3 billion years. Historically viewed as little more than a diffusion barrier between the cytoplasm and the nucleoplasm, the nuclear envelope is now known to have roles in the cell cycle, cytoskeletal stability and cell migration, genome architecture, epigenetics, regulation of transcription, splicing, and DNA replication. Here we will review both what is known and what is speculated about the role of the nuclear envelope in genome organization, particularly with respect to the positioning and repositioning of genes and chromosomes within the nucleus during differentiation. PMID- 21970988 TI - Caenorhabditis elegans as a model system for studying the nuclear lamina and laminopathic diseases. AB - The nuclear lamina is a protein-rich network located directly underneath the inner nuclear membrane of metazoan nuclei. The components of the nuclear lamina have been implicated in nearly all nuclear functions; therefore, understanding the structural, mechanical, and signal transducing properties of these proteins is crucial. In addition, mutations in many of these proteins cause a wide range of human diseases, the laminopathies. The structure, function, and interaction of the lamina proteins are conserved among metazoans, emphasizing their fundamental roles in the nucleus. Several of the advances in the field of the nuclear lamina have come from studies performed in Caenorhabditis elegans or on C. elegans proteins expressed in vitro. Here, we discuss the current knowledge about the nuclear lamina, including an overview of the technical tools offered by C. elegans that make it a powerful model organism for the study of the nuclear lamina and laminopathic diseases. PMID- 21970989 TI - A top-down analysis of Xa- and Xi-territories reveals differences of higher order structure at >= 20 Mb genomic length scales. AB - The active and inactive X (Xa;Xi) territory with its seemingly highly compacted Barr body in nuclei of female mammalian cells provide a key example for studies of structure/function relationships in homologous chromosomes with different functional properties. Here we used about 300 human X-specific large insert clones to generate probe sets, which target physically or functionally defined sub-chromosomal segments. We combined 3D multicolor FISH with quantitative 3D image analysis in order to compare the higher order organization in Xi-and Xa territories in human diploid fibroblasts (HDFs) at various length scales ranging from about 50 Mb down to 1 Mb. Xi-territories were characterized by a rounder shape as compared to the flatter and more extended shape of Xa-territories. The overall compaction of the entire Xi-territory, including the Barr body, was only 1.2-fold higher than the Xa-territory. Significant differences, however, were noted between distinct subchromosomal segments: At 20 Mb length scales higher compaction in Xi-territories was restricted to specific segments, but higher compaction in these segments was not correlated with gene density, transcriptional activity, LINE content or histone markers locally enriched in Xi territories. Notably, higher compaction in Xi-territories observed for 20 Mb segments was not reflected accordingly by inclosed segments of 1-4 Mb. We conclude that compaction differences result mainly from a regrouping of ~1 Mb chromatin domains rather than from an increased condensation of individual domains. In contrast to a previous report, genes subject to inactivation as well as escaping from inactivation were not excluded from the interior of the Barr body. PMID- 21970990 TI - Nonconscious attention bias to threat is correlated with anterior cingulate cortex gray matter volume: a voxel-based morphometry result and replication. AB - An important aspect of the fear response is the allocation of spatial attention toward threatening stimuli. This response is so powerful that modulations in spatial attention can occur automatically without conscious awareness. Functional neuroimaging research suggests that the amygdala and anterior cingulate cortex (ACC) form a network involved in the rapid orienting of attention to threat. A hyper-responsive attention bias to threat is a common component of anxiety disorders. Yet, little is known of how individual differences in underlying brain morphometry relate to variability in attention bias to threat. Here, we performed two experiments using dot-probe tasks that measured individuals' attention bias to backward masked fearful faces. We collected whole-brain structural magnetic resonance images and used voxel-based morphometry to measure brain morphometry. We tested the hypothesis that reduced gray matter within the amygdala and ACC would be associated with reduced attention bias to threat. In Experiment 1, we found that backward masked fearful faces captured spatial attention and that elevated attention bias to masked threat was associated with greater ACC gray matter volumes. In Experiment 2, this association was replicated in a separate sample. Thus, we provide initial and replicating evidence that ACC gray matter volume is correlated with biased attention to threat. Importantly, we demonstrate that variability in affective attention bias within the healthy population is associated with ACC morphometry. This result opens the door for future research into the underlying brain morphometry associated with attention bias in clinically anxious populations. PMID- 21970991 TI - A 14-year-old with rectal bleeding and abdominal pain. PMID- 21970992 TI - Thinking outside the box when dealing with patients with GERD and feeding problems. PMID- 21970993 TI - Zinc monotherapy from time of diagnosis for young pediatric patients with presymptomatic Wilson disease. AB - In 4 young pediatric patients with presymptomatic Wilson disease, we found zinc monotherapy beginning at time of diagnosis to be safe and highly effective for follow-up intervals between 1 and 2 years. Such maintenance therapy with zinc can maintain urinary copper excretion between 1 and 3 MUg . kg(-1) . day. PMID- 21970994 TI - Impaired mucosal barrier function in the small intestine of the cystic fibrosis mouse. AB - OBJECTIVES: The intestinal mucosal barrier protects the body from the large numbers of microbes that inhabit the intestines and the molecules they release. Intestinal barrier function is impaired in humans with cystic fibrosis (CF), including reduced activity of the lipopolysaccharide-detoxifying enzyme intestinal alkaline phosphatase (IAP) and increased permeability. The objective of this study was to determine the suitability of using the CF mouse to investigate intestinal barrier function, and whether interventions that are beneficial for the CF mouse intestinal phenotype (antibiotics or laxative), would improve barrier function. Also tested were the effects of exogenous IAP administration. MATERIALS AND METHODS: The Cftr(tm1UNC) mouse was used. IAP expression (encoded by the murine Akp3 gene) was measured by quantitative reverse transcription-polymerase chain reaction and enzyme activity. Intestinal permeability was assessed by measuring rhodamine-dextran plasma levels following gavage. RESULTS: CF mice had 40% Akp3 mRNA expression and 30% IAP enzyme activity, as compared with wild-type mice. Oral antibiotics and laxative treatments normalized Akp3 expression and IAP enzyme activity in the CF intestine. CF mice had a 5-fold greater transfer of rhodamine-dextran from gut lumen to blood. Antibiotic and laxative treatments reduced intestinal permeability in CF mice. Administration of exogenous purified IAP to CF mice reduced intestinal permeability to wild-type levels and reduced small intestinal bacterial overgrowth by >80%. CONCLUSIONS: The CF mouse intestine has impaired mucosal barrier function, similar to human CF. Interventions that improve other aspects of the CF intestinal phenotype (antibiotics and laxative) also increase IAP activity and decrease intestinal permeability in CF mice. Exogenous IAP improve permeability and strongly reduce bacterial overgrowth in CF mice, suggesting this may be a useful therapy for CF. PMID- 21970995 TI - Detection of pepsinogen in the neonatal lung and stomach by immunohistochemistry. AB - OBJECTIVE: Evaluate the hypothesis that the same pepsinogen C molecule produced in the stomach is also produced by the lung. PATIENTS AND METHODS: Pulmonary and gastric tissues collected postmortem were immunohistochemically stained for pepsinogen C and pepsinogen A. RESULTS: Sixteen patients with diverse causes of death were evaluated. Gestational age at birth ranged between 21 and 37 weeks. Pepsinogen A was detected in 12 of the 13 stomach sections, mainly in the chief cells, but not in any lung sections. Pepsinogen C was detected in all stomach sections in chief and mucus cells and in 9 of the 16 lung sections, mainly in type II pneumocytes. Pepsinogen C was not detected in the 3 lung cases with a gestational age <23 weeks. CONCLUSIONS: The same pepsinogen C molecule is produced in the stomach and in the lung. These findings potentially affect previous study results that used an enzymatic pepsin detection assay to evaluate for and associate gastroesophageal reflux disease with other morbidities. PMID- 21970997 TI - Amanita poisoning and liver transplantation: do we have the right decision criteria? PMID- 21970996 TI - Siglec-F inhibition reduces esophageal eosinophilia and angiogenesis in a mouse model of eosinophilic esophagitis. AB - OBJECTIVES: Eosinophilic esophagitis (EoE) is a disorder characterized histologically by tissue eosinophilia. Sialic acid-binding immunoglobulin-like lectin (Siglec-F) is a receptor highly expressed on mouse eosinophils and mediates eosinophilic apoptosis. We investigated whether administration of an anti-Siglec-F Ab would reduce esophageal eosinophilic inflammation and remodeling in a mouse model of egg ovalbumin (OVA)-induced EoE. SUBJECTS AND METHODS: Three groups of mice were studied (no OVA, OVA + anti-Siglec-F Ab, and OVA + isotype control Ab). Mice were sensitized intraperitoneally and then challenged chronically with intraesophageal OVA. Levels of esophageal eosinophils and features of remodeling (angiogenesis, vascular endothelial growth factor expression, deposition of fibronectin, basal zone hyperplasia, and fibrosis) were quantitated by immunohistochemistry and image analysis. RESULTS: Administration of an anti-Siglec-F Ab to OVA-challenged mice significantly reduced levels of esophageal eosinophils, down to levels noted in non-OVA-challenged mice. The anti Siglec-F Ab also reduced features of OVA-induced remodeling, including angiogenesis, basal zone hyperplasia, and fibronectin deposition. The reduced angiogenesis in anti-Siglec-F Ab-treated mice was associated with reduced numbers of vascular endothelial growth factor-positive cells in the esophagus. The anti Siglec-F antibody did not significantly reduce esophageal fibrosis as assessed by trichrome staining. CONCLUSIONS: Administration of an anti-Siglec-F antibody significantly decreased the number of eosinophils in the esophagus in a mouse model of OVA-induced EoE. The reduction in eosinophilic inflammation was associated with a significant decrease in levels of angiogenesis, deposition of fibronectin, and basal zone hyperplasia. Studies in this pre-clinical model of EoE suggest that Siglec-F (and its human paralog Siglec-8) may be novel therapeutic targets to reduce eosinophilic inflammation in EoE. PMID- 21970998 TI - Duchenne and Becker muscular dystrophy presenting as nonalcoholic fatty liver disease. PMID- 21970999 TI - Endoscopic management of transanal protrusion of subdural peritoneal shunt in a child. PMID- 21971000 TI - Structural properties of human monoamine oxidases A and B. AB - The structural elucidations of human monoamine oxidases A and B (MAO-A and -B) have provided novel insights into their similarities and differences. Although the enzymes exhibit ~70% sequence identities, highly conserved chain folds, and are structurally identical in their flavin adenine dinucleotide (FAD)-binding sites, they differ considerably in the structures of their active sites opposite the flavin cofactor. MAO-A has a monopartite cavity of ~550 A3, and MAO-B exhibits a bipartite cavity structure with an entrance cavity of 290 A3 and a substrate cavity of ~400 A3. Ile199 functions as a conformational "gate" separating the two cavities. Both enzymes are anchored to the outer mitochondrial membrane via C-terminal helical tails. Loop structures are found at the entrances to their active sites at the membrane surface. Although the crystal structure of human MAO-A is monomeric while MAO-B is dimeric, both enzymes are dimeric in their membrane-bound forms. Dimerization may be important for the favorable orientation of the resultant protein dipole moment toward the anionic membrane surface. PMID- 21971002 TI - Kinetic behavior and reversible inhibition of monoamine oxidases--enzymes that many want dead. AB - Monoamine oxidase (MAO) inhibitors have proven to be valuable tools in pharmacology and therapeutics. This account concerns the behavior of the different types of reversible inhibitor and how an understanding of the kinetic mechanisms of MAO may help in their design. PMID- 21971003 TI - The pharmacology of selegiline. AB - Selegiline, the R-optical enantiomer of deprenyl (phenyl-isopropyl-methyl propargylamine), was almost exclusively used MAO-B inhibitor during the past decades to treat Parkinson's disease. Oral treatment prolongs the need of levodopa administration. Selegiline is rapidly metabolized by the microsomal enzymes to amphetamine, methamphetamine, and desmethyl-deprenyl. In addition, the flavin-containing monooxigenase is synthesizing deprenyl-N-oxide. Selegiline in rather low concentrations (10-9-10-13 M), does not influence MAO-B, but it has an antiapoptotic activity in tissue culture. The neuroprotective effect of selegiline has a biphasic character. In higher concentrations than 10-7 M increases the rate of apoptosis (proapoptotic activity). The metabolites are also taking part in the complex pharmacological activity of selegiline. The simultaneous presence of the pro- and antiapoptotic effects of selegiline and its metabolites frequently hindered its clinical usage. During the past years rasagiline has been introduced to replace selegiline in clinical application. MAO B inhibitors beside their effect on the enzyme MAO-B could hold different spectrum of pharmacological activities. Selegiline is administered orally and it possesses an intensive "first pass" metabolism. To circumvent the "first pass" metabolism, parenteral administration of the drug might lead to different distribution and pharmacological activity of selegiline. PMID- 21971004 TI - Type A monoamine oxidase regulates life and death of neurons in neurodegeneration and neuroprotection. AB - In Parkinson's disease, type B monoamine oxidase (MAO-B) is proposed to play an important role in the pathogenesis through production of reactive oxygen species and neurotoxins from protoxicants, such as 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine. In addition, inhibitors of MAO-B protect neurons in the cellular and animal models of Parkinson's and Alzheimer's diseases. However, the role of type A MAO (MAO-A) in neuronal death and neuroprotection by MAO-B inhibitors has been scarcely elucidated. This chapter presents our recent results on the involvement of MAO-A in the activation of mitochondrial death signal pathway and in the induction of prosurvival genes to prevent cell death with MAO B inhibitors. The roles of MAO-A in the regulation of neuronal survival and death are discussed in concern to find a novel strategy to protect neurons in age associated neurodegenerative disorders and depression. PMID- 21971005 TI - Multimodal drugs and their future for Alzheimer's and Parkinson's disease. AB - This chapter discusses the rationale for developing multimodal or multifunctional drugs (also called designed multiple ligands or DMLs) aimed at disease-modifying treatment strategies for the most common neurodegenerative diseases Alzheimer's and Parkinson's disease (AD and PD). Both the prevalence and incidence of AD and PD have seen consistent and dramatic increases, a disconcerting phenomenon which, ironically, has been attributed to extended life expectancy brought about by better health care globally. In spite of these statistics, the development and introduction to the clinic of new therapies proven to prevent or delay the onset of AD and PD have been disappointing. Evidence has accumulated to suggest that the etiopathology of these diseases is extremely complex, with an array of potential drug targets located within a number of deleterious biochemical pathways. Therefore, in these diseases, it is unlikely that the complex pathoetiological cascade leading to disease initiation or progression will be mitigated by any one drug acting on a single pathway or target. The pursuit of novel DMLs may offer far better outcomes. Although certainly not the only, and perhaps not even the best, approach but farthest along the drug development pipeline in the DML paradigm are drugs that combine inhibition of monoamine oxidase with associated etiological targets unique to either AD or PD. These compounds will constitute the major focus of this chapter, which will also explore radically new paradigms that seek to combine cognitive enhancers with proneurogenesis compounds. PMID- 21971001 TI - Behavioral outcomes of monoamine oxidase deficiency: preclinical and clinical evidence. AB - Monoamine oxidase (MAO) isoenzymes A and B are mitochondrial-bound proteins, catalyzing the oxidative deamination of monoamine neurotransmitters as well as xenobiotic amines. Although they derive from a common ancestral progenitor gene, are located at X-chromosome and display 70% structural identity, their substrate preference, regional distribution, and physiological role are divergent. In fact, while MAO-A has high affinity for serotonin and norepinephrine, MAO-B primarily serves the catabolism of 2-phenylethylamine (PEA) and contributes to the degradation of other trace amines and dopamine. Convergent lines of preclinical and clinical evidence indicate that variations in MAO enzymatic activity--due to either genetic or environmental factors--can exert a profound influence on behavioral regulation and play a role in the pathophysiology of a large spectrum of mental and neurodegenerative disorders, ranging from antisocial personality disorder to Parkinson's disease. Over the past few years, numerous advances have been made in our understanding of the phenotypical variations associated with genetic polymorphisms and mutations of the genes encoding for both isoenzymes. In particular, novel findings on the phenotypes of MAO-deficient mice are highlighting novel potential implications of both isoenzymes in a broad spectrum of mental disorders, ranging from autism and anxiety to impulse-control disorders and ADHD. These studies will lay the foundation for future research on the neurobiological and neurochemical bases of these pathological conditions, as well as the role of gene * environment interactions in the vulnerability to several mental disorders. PMID- 21971006 TI - Neuroprotective profile of the multitarget drug rasagiline in Parkinson's disease. AB - Monoamine oxidase (MAO) inhibitors were reported to have therapeutic value in several common neurodegenerative conditions owed to their diverse pharmacological functions in neuron survival. Rasagiline (N-propargyl-1-(R)-aminoindan) is a novel, highly potent irreversible MAO-B inhibitor in the treatment of Parkinson's disease (PD). It has been demonstrated to be neuroprotective in PD model systems by preventing the formation of reactive oxygen species derived from prevention of derived from oxidation of dopamine by MAO-B and via an antiapoptotic action, which appears to be independent of MAO-B inhibition and related to its embedded N propargyl moiety. This review reflects on earlier and present evidence supporting a role for rasagiline as a neuroprotective molecule in the treatment of PD. PMID- 21971007 TI - Rasagiline in Parkinson's disease. AB - It has long been recognized that monoamine oxidase (MAO) inhibitors have a role in the management of Parkinson's disease (PD). The MAO-B inhibitor rasagiline has neuroprotective effects in animal models, mediated partly by its antiapoptotic activity. Rasagiline has been shown to be effective as monotherapy for early PD and as an adjunct to dopaminergic therapy. Clinical trials have also shown putative disease-modifying effects, though rasagiline's potential to alter the long-term course of PD remains controversial. Given the demonstrated benefits of rasagiline, along with its safety and tolerability profile, it has an important role to play in PD therapy. PMID- 21971008 TI - Selective inhibitors of monoamine oxidase type B and the "cheese effect". AB - Potentiation of the cardiovascular and other effects of dietary tyramine by monoamine oxidase (MAO) inhibitors (cheese effect) has been a major limitation to clinical use of these drugs. The discovery that MAO exists in two distinct isoforms, MAO-A and MAO-B, together with the development of selective inhibitors of each isoform, enabled the understanding that selective inhibition of MAO-A, or inhibition of both isoforms, will cause cheese effect, but selective inhibition of MAO-B can be elicited without dangerous pressor reaction. This development has permitted the introduction of selective MAO-B inhibitors to clinical medicine for treatment of Parkinson's disease. This review describes the basic mechanisms involved in cheese effect, as well as providing information on tyramine levels in a variety of foodstuff, and surveys clinical information from tyramine pressor testing with the selective MAO-B inhibitors, selegiline and rasagiline. PMID- 21971009 TI - A novel anti-Alzheimer's disease drug, ladostigil neuroprotective, multimodal brain-selective monoamine oxidase and cholinesterase inhibitor. AB - The novel therapeutic strategy in which drug candidates are designed to possess diverse pharmacological properties and act on multiple targets has stimulated the development of the multimodal drug, ladostigil [(N-propargyl-(3R) aminoindan-5yl) ethyl methyl carbamate]. Ladostigil combines neuroprotective effects with monoamine oxidase-A and -B and cholinesterase inhibitory activities in a single molecule, presently in a Phase IIb clinical trial and intended for the treatment of Alzheimer's disease, and dementia comorbid with extrapyramidal disorders and depression. This chapter will discuss the preclinical scientific evidence for the therapeutic potential use of ladostigil in the clinic and molecular signaling pathways that are considered to be involved in the molecular activities of the drug. PMID- 21971010 TI - Novel MAO-B inhibitors: potential therapeutic use of the selective MAO-B inhibitor PF9601N in Parkinson's disease. AB - Parkinson's disease (PD) is a neurodegenerative disease that is characterized by preferential loss of dopaminergic neurons in the substantia nigra pars compacta, leading to declining levels of dopamine in the striatum. In our search for compounds able not only to extend the effects of dopamine by preventing its degradation but also to halt or slow the neurodegenerative process, we designed, synthesized, and biologically tested a series of propargylamines for their potential use as therapeutic agents for PD. Among them, PF9601N, [N-(2-propynyl) 2-(5-benzyloxy-indolyl) methylamine], showed high potency and selectivity as a MAO-BI (monoamine oxidase type B inhibitor) and also demonstrated remarkable neuroprotective properties in several in vivo and cellular models of PD. In this chapter, we describe the preclinical evidence revealing the novel MAO-BI PF9601N as an interesting candidate for the treatment of PD. PMID- 21971011 TI - Monoamine oxidase and their inhibitors. Preface. PMID- 21971012 TI - Amorphous tunable-size Co-B magnetic nanoparticles from the cobalt-catalyzed NaBH4 hydrolysis. AB - The cobalt-catalyzed hydrolysis of sodium borohydride (NaBH(4)) has become an attractive process in view of the possibilities of using the hydride for hydrogen storage material and also for the production of amorphous and tunable-size magnetic nanoparticles. This process in which the metallic catalyst transforms into a Co- and B-based magnetic by-product when in contact with NaBH(4) has been modified in order to control the mechanism of formation, tune the final size and study the particular magnetic behavior of the Co-B alloy nanoparticles provided. PMID- 21971013 TI - Ethyl-eicosapentaenoate (E-EPA) attenuates motor impairments and inflammation in the MPTP-probenecid mouse model of Parkinson's disease. AB - Parkinson's disease (PD) is a neurodegenerative disorder, characterized by hypokinesia, but also mood and cognitive disorders. Neuropathologically, PD involves loss of nigrostriatal dopamine (DA) and secondary non-dopaminergic abnormalities. Inflammation may contribute to PD pathogenesis, evident by increased production of pro-inflammatory cytokines. PD onset has been positively associated with dietary intake of omega-(n)-6 polyunsaturated fatty acids (PUFA). On the other hand, omega-(n)-3 PUFA may benefit PD. One of these n-3 PUFA, eicosapentaenoic acid (EPA), is a neuroprotective lipid with anti-inflammatory properties, but its neuroprotective effects in PD are unknown. Thus, we presently tested the hypothesis that EPA can protect against behavioral impairments, neurodegeneration and inflammation in the 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-probenecid (MPTP-P) mouse model of PD. MPTP-P injections caused hypokinesia in the rotorod and pole test, hyperactivity in the open field, and impaired mice on the cued version (procedural memory) of the Morris water maze. MPTP-P caused a loss of nigrostriatal DA and altered neurochemistry in the frontal cortex and hippocampus. Furthermore, striatal levels of pro-inflammatory cytokines were increased, while the brain n-3/n-6 lipid profile remained unaltered. Feeding mice a 0.8% ethyl-eicosapentaenoate (E EPA) diet prior to MPTP-P injections increased brain EPA and docosapentaenoic acid (DPA) but not docosahexaenoic acid (DHA) or n-6 PUFA. The diet attenuated the hypokinesia induced by MPTP-P and ameliorated the procedural memory deficit. E-EPA also suppressed the production of pro-inflammatory cytokines. However, E EPA did not prevent nigrostriatal DA loss. Based on this partial protective effect of E-EPA, further testing may be warranted. PMID- 21971014 TI - Finding the right motivation: genotype-dependent differences in effective reinforcements for spatial learning. AB - Memory impairments of DBA/2J mice have been frequently reported in spatial and emotional behavior tests. However, in some memory tests involving food reward, DBA/2J mice perform equally well to C57BL/6J mice or even outperform them. Thus, it is conceivable that motivational factors differentially affect cognitive performance of different mouse strains. Therefore, spatial memory of DBA/2J and C57BL/6J mice was investigated in a modified version of the Barnes maze (mBM) test with increased complexity. The modified Barnes maze test allowed using either aversive or appetitive reinforcement, but with identical spatial cues and motor requirements. Both mouse strains acquired spatial learning in mBM tests with either reinforcement. However, DBA/2J mice learned slower than C57BL/6J mice when aversive reinforcement was used. In contrast, the two strains performed equally well when appetitive reinforcement was used. The superior performance in C57BL/6J mice in the aversive version of the mBM test was accompanied by a more frequent use of the spatial strategy. In the appetitive version of the mBM test, both strains used the spatial strategy to a similar extent. The present results demonstrate that the cognitive performance of mice depends heavily on motivational factors. Our findings underscore the importance of an effective experimental design when assessing spatial memory and challenges interpretations of impaired hippocampal function in DBA/2J mice drawn on the basis of behavior tests depending on aversive reinforcement. PMID- 21971015 TI - Behavioural and cognitive profiles of mouse models for Prader-Willi syndrome. AB - Prader-Willi syndrome (PWS) is a neurodevelopmental disorder with aspects of psychiatric illness caused by genetic mutations at chromosome 15q11-q13. In addition to causing PWS, this interval is also thought to be of importance more generally in the development of autism and psychotic illness. The PWS genetic interval is conserved in mammals, and consequently mice carrying genetic manipulations affecting one or all of the genes in the region of conserved synteny have been generated and used in neurobehavioural studies. Here we give an overview of these models and describe the behavioural and neurobiological analyses that have been performed, many of which have provide new insights into the molecular and neural processes influenced by genes within the PWS interval. PMID- 21971017 TI - Larval fat body cells die during the early pupal stage in the frame of metamorphosis remodelation in Bombyx mori. AB - In holometabolus insects, morphology of the larval fat body is remodeled during metamorphosis. In higher Diptera, remodeling of the fat body is achieved by cell death of larval fat body cells and differentiation of the adult fat body from primordial cells. However, little is known about remodeling of the fat body at pupal metamorphosis in Lepidoptera. In this study, we found that cell death of the larval fat body in Bombyx mori occurs at shortly after pupation. About 30% of the fat body cells underwent cell death on days 1 and 2 after pupation. The cell death involved genomic DNA fragmentation, a characteristic of apoptosis. Surgical manipulation and in vitro culture of fat body cells revealed that 20 hydroxyecdysone and juvenile hormone had no effect on either initiation or progression of cell death. During cell death, a large increase in activity of caspase-3, a key enzyme of cell death, was observed. Western blot analysis of the active form of caspase-3-like protein revealed that the length of caspase-3 of B. mori was much larger than that of caspase-3 in other species. The results suggest that larval fat body cells of B. mori are removed through cell death, which is mediated by a caspase probably categorized in a novel family. PMID- 21971018 TI - Existing and emerging strategies for the synthesis of nanoscale heterostructures. AB - Development of new multifunctional nanostructures relies on the ability to make new materials at the nanoscale with control over size, shape and composition. While this control is extremely important to tune several properties, an alternative strategy is to create active interfaces between two or more nanostructures to form nanoscale heterostructures. In these heterostructures, the interfaces play a key role in stabilizing and enhancing the efficiency of the individual components for various applications. In this article, we discuss synthesis methods of different types of nanoscale heterostructures and the role of interfaces in various applications. We present the current state-of-the-art in designing heterostructures and possible upcoming synthetic strategies with their advantages and disadvantages. We present how such heterostructures are highly efficient for catalytic, photovoltaic and nanoelectronic applications drawing several examples from our own studies and from the literature. PMID- 21971019 TI - The diffusion of hydrogen monomers on hole-doped graphitic lattices: over-barrier transition and quantum tunneling. AB - The diffusion of hydrogen and deuterium monomers on hole-doped graphene (a planar graphitic lattice), the outside wall and the inside wall of hole-doped (6, 0) single-walled carbon nanotubes (a curved graphitic lattice) was investigated using density functional theory and density functional perturbation theory. The jump frequencies for the over-barrier transition and phonon-assisted quantum tunneling were calculated by transition state theory and small-polaron theory, respectively. The effects of the local curvature of the surface and the hole doping on the thermodynamic and kinetic properties of a hydrogen monomer on these graphitic lattices are discussed. Our results demonstrate that it is sufficient to judge the diffusional mobility of a hydrogen monomer on graphitic lattices from just the over-barrier transition, no matter how much it is curved and hole doped, while the quantum tunneling can be safely neglected because it is significantly suppressed by the covalent bonding of hydrogen with the graphitic lattice. PMID- 21971020 TI - Pretreatment with pentoxifylline has antidepressant-like effects in a rat model of acute myocardial infarction. AB - We have observed that, after myocardial infarction (MI), rats display apoptosis in the limbic system that can be prevented by pentoxifylline (PTX), a proinflammatory cytokine inhibitor. We have hypothesized that reduction of apoptosis in the limbic system can attenuate the depressive behaviour occurring post-MI. The present study was, therefore, designed to assess the outcome of PTX on depressive behaviour manifesting after MI. Myocardial ischaemia, induced for 40 min in male Sprague-Dawley rats, was followed by reperfusion (MI groups). Sham groups were subjected to the same protocol without occlusion. PTX (10 mg/kg/day) or saline was administered intraperitoneally 15 min before ischaemia, and then every day until sacrifice. Two weeks after ischaemia, depression was evaluated by the forced swim test and the sucrose preference test. At the end of the experiment, the animals were sacrificed, and myocardial infarct size was examined along with plasma IL-1beta concentrations. MI rats drank less sucrose in the sucrose preference test and were more immobile in the forced swim test than the sham controls. PTX reversed these behaviours in the MI group to a level similar to that in the untreated sham group, without affecting infarct size. PTX reduced plasma IL-1beta concentrations in both sham and MI rats. We conclude that PTX administration significantly reverses the depressive-like behaviour seen after MI in rats. PMID- 21971022 TI - From the editor. PMID- 21971021 TI - Metabotropic glutamate antagonists alone and in combination with morphine: comparison across two models of acute pain and a model of persistent, inflammatory pain. AB - The present study examined the effects of the mGluR1 antagonist JNJ16259685 (JNJ) and the mGluR5 antagonist 2-methyl-6-phenylethynylpyridine (MPEP) alone and in combination with morphine in two acute pain models (hotplate, warm water tail withdrawal), and a persistent, inflammatory pain model (capsaicin). In the hotplate and warm water tail-withdrawal procedures, JNJ and MPEP were ineffective when administered alone. In both procedures, JNJ potentiated morphine antinociception. In the hotplate procedure, MPEP potentiated morphine antinociception at the highest dose examined, whereas in the warm water tail withdrawal procedure MPEP attenuated morphine antinociception at a moderate dose and potentiated morphine antinociception at a high dose. For both JNJ and MPEP, the magnitude of this morphine potentiation was considerably greater in the hotplate procedure. In the capsaicin procedure, the highest dose of MPEP produced intermediate levels of antihyperalgesia and also attenuated the effects of a dose of morphine that produced intermediate levels of antihyperalgesia. In contrast, JNJ had no effect when administered alone in the capsaicin procedure and did not alter morphine-induced antihyperalgesia. The present findings suggest that the effects produced by mGluR1 and mGluR5 antagonists alone and in combination with morphine can be differentiated in models of both acute and persistent pain. PMID- 21971023 TI - Challenges and benefits of adding laboratory data to a mortality risk adjustment method. AB - BACKGROUND: There is increased interest in improving the clinical acceptance and statistical performance of hospital mortality rate comparisons. This study assessed the feasibility of linking separate electronic feeds of laboratory data and claims-based information and, if successful, to identify laboratory data elements that significantly improved mortality rate predictions for All-Patient Refined Diagnosis Related Groups (APRDRGs), a risk of mortality (ROM) classification tool in regular use for public reporting purposes. METHODS: The Florida Agency for Health Care Administration recruited 15 hospitals to supply computerized administrative and laboratory information that could be linked at the patient level. The hospitals, standardized computer code terminology, which was then merged with administrative data. We evaluated the ability of the merged data to improve APRDRG ROM predictions. RESULTS: We describe the procedures that the laboratory information systems used to link the electronic laboratory data with standard claims data. The addition of 11 clinical laboratory test results increased the C statistic by 0.574% and R2 by 4.53%. CONCLUSIONS: This study supports the feasibility of linking laboratory data elements with claims-based administrative data to enhance ROM assessments. This linkage resulted in modest statistical improvement in a commonly used ROM model. PMID- 21971024 TI - Measuring sustainability within the Veterans Administration Mental Health System Redesign initiative. AB - OBJECTIVE: To examine how attributes affecting sustainability differ across Veterans Health Administration organizational components and by staff characteristics. SUBJECTS: Surveys of 870 change team members and 50 staff interviews within the Veterans Affairs' Mental Health System Redesign initiative. METHODS: A 1-way ANOVA with a Tukey post hoc test examined differences in sustainability by Veteran Integrated Service Networks, job classification, and tenure from staff survey data of the Sustainability Index. Qualitative interviews used an iterative process to identify "a priori" and "in vivo" themes. A simple stepwise linear regression explored predictors of sustainability. RESULTS: Sustainability differed across Veteran Integrated Service Networks and staff tenure. Job classification differences existed for the following: (1) benefits and credibility of the change and (2) staff involvement and attitudes toward change. Sustainability barriers were staff and institutional resistance and nonsupportive leadership. Facilitators were commitment to veterans, strong leadership, and use of quality improvement tools. Sustainability predictors were outcomes tracking, regular reporting, and use of Plan, Do, Study, Adjust cycles. CONCLUSIONS: Creating homogeneous implementation and sustainability processes across a national health system is difficult. Despite the Veterans Affairs' best evidence-based implementation efforts, there was significant variance. Locally tailored interventions might better support sustainability than "one-size-fits all" approaches. Further research is needed to understand how participation in a quality improvement collaborative affects sustainability. PMID- 21971025 TI - Evidence-based refinement of health and social services: exploring the possibilities of intravention research. AB - To promote evidence-based refinement of quality health and social services delivery and care, decision makers, researchers, and practitioners often undertake intervention research. Intervention research tests and describes new strategies for achieving desired outcomes. But theoretical, methodological, and practical issues continue to plague even alternative participatory approaches to intervention research, raising questions about its potential for promoting quality health and social services and care. In response to this persistent challenge, the authors of this article propose a radical solution, namely intravention research, laying out its unique features as well as its theoretical and practical implications. Their conceptualization sets the stage for dialogue on options for advancing research methodologies and methods that might better promote evidence-informed health and social services. PMID- 21971026 TI - Effect of surgical safety checklists on postoperative morbidity and mortality rates, Shiraz, Faghihy Hospital, a 1-year study. AB - OBJECTIVE: The study intent was to (1) encourage the use of surgical safety checklists and (2) measure the effect checklists have in reducing surgical complications. DESIGN: An interventional study designed to improve postsurgical outcomes was performed. SETTING: The study site was a 374-bed referral educational hospital in Shiraz, Iran, with 6 operating rooms. The study lasted 6 months. PARTICIPANTS: Patient selection involved a convenient sampling method with all eligible patients entering. INTERVENTION: Our checklist covered 3 surgical stages--before anesthesia, immediately before an incision, and before moving the patient to a recovery room. Persons included were operating room team members. MAIN OUTCOME MEASURES: Rates of postsurgical complication before and after application of the surgical safety checklist underwent comparison. RESULTS: Incidence of any complication before and after intervention was 22.9% and 10% (P = .03). Five checklist items were in total compliance. The most common complication was surgical site infection. Implementation of the checklist, responsibility in 2 stages, such as time out and sign out, were significant (P < .05). In most cases, these items reflected the performance of surgeons and anesthesia professionals as compared with the World Health Organization Surgical Safety Checklist. CONCLUSION: Complications decreased by 57% after intervention. Both high patient information detection and elevated levels of cooperation by surgical personnel were observed. Compliance likely helped prevent some adverse effects associated with surgery. PMID- 21971027 TI - Role of quality improvement in prevention of inappropriate transfusions. AB - PURPOSE: Many different methods are used to manage surgical bleeding and reduce transfusion. Techniques vary by institution, resulting in inconsistent outcomes. We reviewed the current literature on the quality and costs of transfusions, focusing on prevention and management of transfusions during surgery, and provide recommendations on future directions for quality improvement (QI). DATA SOURCES: Ovid, PubMed, and Scopus. STUDY SELECTION: Key words included QI, blood loss, transfusion, hemostasis, and costs. Inclusion criteria were English language, publication between 1999 and 2010, and primary end points of blood loss, transfusion, or hemostasis. DATA EXTRACTION: A total of 1331 abstracts were reviewed; 43 met the inclusion criteria. RESULTS: A variety of bleeding management (BM) techniques were identified, with multiple studies suggesting that algorithms combining pre-, peri-, and postoperative interventions have the greatest potential to minimize transfusions. Most studies assessing the economic impact of BM interventions excluded resources beyond blood acquisition cost and longer-term complications, which may underestimate transfusion costs and bias estimates of the cost-effectiveness of interventions. Despite consensus on avoiding inappropriate transfusions, little agreement exists on optimal use of interventions. CONCLUSIONS: Multifaceted algorithms show promising results. Future QI should focus on reducing practice variation via evidence-based guidelines for effective use of BM interventions. PMID- 21971028 TI - An evolution in blood management: past, present, and future. AB - Blood management is a concept that adopts a principle of improving patient outcome by integrating all available techniques to ensure safety, availability, and appropriate allocation of blood products. This constitutes a model of multidisciplinary care where the changes in culture are system directed on the basis of evidence-based medicine. There are about 14% US hospitals where any kind of blood management program exists, although the idea remains the same but the programs vary in their execution, implementation, and ultimately providing the value to patients. In this article, we have described our experience of creating a patient-centric, cost-effective, evidence-based, and multipronged program creation with scalable results. The use of data, education, process improvement, engagement, and accountability of caregivers have resulted in sustained results and helped in creating a comprehensive blood management program. PMID- 21971029 TI - The impact of a temporary medical ward closure on emergency department and hospital service delivery outcomes. AB - OBJECTIVE: To describe the effect of a 3-week closure of a 28-bed medical ward on Emergency Department (ED) and hospital outcomes. METHODS: This was a prospective comparative observational study of all ED attendances (visits; n = 11 383) made to a regional teaching hospital in Queensland, Australia, during a 9-week period (November 24, 2008-January 4, 2009). A 3-week period of ward closure was compared with equal time periods before and after. Hospital health information systems data were linked manually to describe and compare outcomes: median ED length of stay, access block, hospital length of stay, and in-hospital mortality. RESULTS: Ward closure reduced hospital bed capacity by 5.9%. During ward closure there was a higher proportion of access block (38% vs 33% in both pre- and posttimes), longer wait time to see a doctor, and longer overall ED length of stay, compared with pre-ward closure time period. CONCLUSION: Temporarily closing a medical ward had a negative effect on some ED and hospital outcomes. When major refurbishments are required, alternative capacity measures need to be considered to minimize the impact on health service delivery and patient outcomes. Reducing elective surgery and opening replacement beds elsewhere in the hospital are possible solutions. PMID- 21971030 TI - Optimizing the patient transport function at Mayo Clinic. AB - In this article, we report on the implementation of a computerized scheduling tool to optimize staffing for patient transport at the Mayo Clinic. The tool was developed and implemented in Microsoft Excel and Visual Basic for Applications and includes an easy-to-use interface. The tool allows transport management to consider the trade-offs between patient waiting time and staffing levels. While improved staffing efficiency was a desire of the project, it was important that patient service quality was also maintained. The results show that staffing could be reduced while maintaining historical patient service levels. PMID- 21971031 TI - A system for using patient complaints as a trigger to improve quality. AB - This study aims to explore how hospital organizations can use complaints to drive quality improvement. A teaching hospital in Taiwan was purposefully selected as a case study. Data were collected from a variety of sources, including interview with key managers and social workers, questionnaire survey of managers (n = 53), interview with government organizations (n = 4) and nongovernment organizations (n = 3), document collection and review, and the Critical Incident Technique using a questionnaire and nonparticipant observation (n = 59). This study revealed that the case hospital attempted to resolve complaints on a case-by-case basis. But it did not act on these complaints as a collective group to identify systemic problems and deficiencies. This approach provides single-loop learning, which may be sufficient to handle the problem on hand but is not enough to prevent such problems occurring again in the future. This study suggests some implications in regard to a best practice system for using complaints to improve quality. PMID- 21971034 TI - Low-dose gamma-rays and simulated solar particle event protons modify splenocyte gene and cytokine expression patterns. AB - The goal was to investigate the T helper (Th) response in splenocytes of mice exposed to low-dose/low-dose-rate (LDR) gamma-rays, simulated solar particle event protons (sSPE), or combination of both. C57BL/6 mice were exposed to LDR gamma-radiation ((57)Co) to a total dose of 0.05 Gray (Gy) at 0.024 cGy/h, either with or without subsequent exposure to 2 Gy sSPE protons. Expression of genes related to Th cells was evaluated immediately after exposure (day 0). On day 21, intra- and extracellular cytokine production was assessed after activation with anti-CD3 monoclonal antibodies (mAb) or phorbol 12-myristate 13-acetate/ionophore (PMA/I). Five genes were significantly modulated on day 0 in one or more of the irradiated groups compared to controls (p < 0.05): Ccl11, Ccr5, Cd80, Inha, and Il9. On day 21, numbers of cells positive for interferon-gamma were high in the LDR + sSPE group versus 0 Gy and LDR gamma-rays (p < 0.05), but there was no difference in IL-2 and TNF-alpha. Levels of secreted cytokines after anti-CD3 mAb activation were high for 5 (MIP-1alpha, GM-CSF, IFN-gamma, TNF-alpha, IL-13) and low for 2 (IL-7, IL-9) in all irradiated groups. Priming with LDR photons had a significant effect on IFN-gamma and IL-17 compared to sSPE protons alone; IL-2 was low only in the LDR + sSPE group. The cytokine patterns after anti-PMA/I activation were different compared to anti-CD3 mAb and with fewer differences among groups. The data show that total-body exposure to space-relevant radiation has profound effects on Th cell status and that priming with LDR gamma-rays can in some cases modulate the response to sSPE. PMID- 21971035 TI - Mitigation of ionizing radiation-induced bone marrow suppression by p38 inhibition and G-CSF administration. AB - p38 mitogen-activated protein kinases (p38) has been shown to be activated in hematopoietic stem and progenitors cells after exposure to ionizing radiation (IR) and its activation has been implicated in bone marrow (BM) suppression under various pathological conditions. Therefore, in the present study we investigated whether inhibition of p38 activity alone with SB203580 (SB, a specific p38 inhibitor) or in combination with granulocyte colony-stimulating factor (G-CSF) can mitigate total body irradiation (TBI)-induced BM damage and lethality. Our results showed that p38 inhibition with SB had no significant effect on the 30 day survival rates of the mice exposed to 7.2 Gy TBI when it was used alone but increased the survival of the mice when it was combined with G-CSF. This combined effect may be attributable to a better preservation or stimulation of hematopoietic stem and progenitor cells, because BM cells from SB and G-CSF treated mice produced more colony forming units-granulocyte-macrophage (CFU-GM) and 4-week cobblestone area forming cells (CAFCs) than the cells from either SB or G-CSF-treated mice after TBI in a colony forming cell assay and a CAFC assay, respectively. These findings suggest that the combined therapy with SB and G-GSF is more effective in mitigating TBI-induced acute BM injury than either agent alone. PMID- 21971036 TI - Characterization and radio-resistant function of manganese superoxide dismutase of Rubrobacter radiotolerans. AB - Rubrobacter radiotolerans is the most radio-resistant eubacterium without spore formation in the life cycle, and its D(37) is 16,000 Gy against gamma-rays. To understand the molecular mechanism of the high radio-resistance, we purified and characterized superoxide dismutase (SOD) of this organism as enzymatic radical scavenger, and then analyzed its genetic information. The purified SOD protein formed homo-tetramerization of 24,000 Da-monomer, while maintaining its enzymatic activity against potassium cyanide and hydrogen peroxide. We obtained a partial amino acid sequence of the protein and cloned the gene from it. Sequence analysis of the cloned gene indicated that the protein showed a similarity to other bacterial manganese SODs (Mn-SODs). Sequencing for adjacent regions of the gene showed that the gene had promoter elements with an open reading frame for putative PAS/PAC sensor protein at the 5'-adjacent region. Introduction of the gene into Escherichia coli cells lacking intrinsic SOD genes restored the cellular enzymatic activity and resistance to methyl viologen, indicating the gene at work. A mutant cell harboring this gene also became resistant against gamma-rays. The present results suggest that the protein in question is the Mn SOD of R. radiotolerans, a good candidate as a radio-protection factor for this bacterial radio-resistance. PMID- 21971037 TI - Classification of breast tissue using a laboratory system for small-angle x-ray scattering (SAXS). AB - Structural changes in breast tissue at the nanometre scale have been shown to differentiate between tissue types using synchrotron SAXS techniques. Classification of breast tissues using information acquired from a laboratory SAXS camera source could possibly provide a means of adopting SAXS as a viable diagnostic procedure. Tissue samples were obtained from surgical waste from 66 patients and structural components of the tissues were examined between q = 0.25 and 2.3 nm(-1). Principal component analysis showed that the amplitude of the fifth-order axial Bragg peak, the magnitude of the integrated intensity and the full-width at half-maximum of the fat peak were significantly different between tissue types. A discriminant analysis showed that excellent classification can be achieved; however, only 30% of the tissue samples provided the 16 variables required for classification. This suggests that the presence of disease is represented by a combination of factors, rather than one specific trait. A closer examination of the amorphous scattering intensity showed not only a trend of increased scattering intensity with disease severity, but also a corresponding decrease in the size of the scatterers contributing to this intensity. PMID- 21971038 TI - A WNTer revisit: new faces of beta-catenin and TCFs in pluripotency. AB - New evidence has revealed interesting aspects of how the Wnt-beta-catenin pathway controls self-renewal and lineage differentiation of pluripotent embryonic stem cells. Although Wnt-beta-catenin signaling is dispensable for the self-renewal of naive mouse embryonic stem cells, it facilitates their expansion and resistance to differentiation through an unconventional dual mechanism involving the transcriptional repressor T cell factor (TCF) 3 and the transcriptional activator TCF1. PMID- 21971039 TI - Genome-wide analysis of a Wnt1-regulated transcriptional network implicates neurodegenerative pathways. AB - Wnt proteins are critical to mammalian brain development and function. The canonical Wnt signaling pathway involves the stabilization and nuclear translocation of beta-catenin; however, Wnt also signals through alternative, noncanonical pathways. To gain a systems-level, genome-wide view of Wnt signaling, we analyzed Wnt1-stimulated changes in gene expression by transcriptional microarray analysis in cultured human neural progenitor (hNP) cells at multiple time points over a 72-hour time course. We observed a widespread oscillatory-like pattern of changes in gene expression, involving components of both the canonical and the noncanonical Wnt signaling pathways. A higher-order, systems-level analysis that combined independent component analysis, waveform analysis, and mutual information-based network construction revealed effects on pathways related to cell death and neurodegenerative disease. Wnt effectors were tightly clustered with presenilin1 (PSEN1) and granulin (GRN), which cause dominantly inherited forms of Alzheimer's disease and frontotemporal dementia (FTD), respectively. We further explored a potential link between Wnt1 and GRN and found that Wnt1 decreased GRN expression by hNPs. Conversely, GRN knockdown increased WNT1 expression, demonstrating that Wnt and GRN reciprocally regulate each other. Finally, we provided in vivo validation of the in vitro findings by analyzing gene expression data from individuals with FTD. These unbiased and genome-wide analyses provide evidence for a connection between Wnt signaling and the transcriptional regulation of neurodegenerative disease genes. PMID- 21971040 TI - Itk controls the spatiotemporal organization of T cell activation. AB - During T cell activation by antigen-presenting cells (APCs), the diverse spatiotemporal organization of components of T cell signaling pathways modulates the efficiency of activation. Here, we found that loss of the tyrosine kinase interleukin-2 (IL-2)-inducible T cell kinase (Itk) in mice altered the spatiotemporal distributions of 14 of 16 sensors of T cell signaling molecules in the region of the interface between the T cell and the APC, which reduced the segregation of signaling intermediates into distinct spatiotemporal patterns. Activation of the Rho family guanosine triphosphatase Cdc42 at the center of the cell-cell interface was impaired, although the total cellular amount of active Cdc42 remained intact. The defect in Cdc42 localization resulted in impaired actin accumulation at the T cell-APC interface in Itk-deficient T cells. Reconstitution of cells with active Cdc42 that was specifically directed to the center of the interface restored actin accumulation in Itk-deficient T cells. Itk also controlled the central localization of the guanine nucleotide exchange factor SLAT [Switch-associated protein 70 (SWAP-70)-like adaptor of T cells], which may contribute to the activation of Cdc42 at the center of the interface. Together, these data illustrate how control of the spatiotemporal organization of T cell signaling controls critical aspects of T cell function. PMID- 21971042 TI - Localizing cellular housekeeping. PMID- 21971043 TI - Stem cells: The 'backup' intestinal stem cell. PMID- 21971044 TI - Mechanisms of disease: USP1 keeps ID proteins stable. PMID- 21971041 TI - The nucleoskeleton as a genome-associated dynamic 'network of networks'. AB - In the cytosol, actin polymers, intermediate filaments and microtubules can anchor to cell surface adhesions and interlink to form intricate networks. This cytoskeleton is anchored to the nucleus through LINC (links the nucleoskeleton and cytoskeleton) complexes that span the nuclear envelope and in turn anchor to networks of filaments in the nucleus. The metazoan nucleoskeleton includes nuclear pore-linked filaments, A-type and B-type lamin intermediate filaments, nuclear mitotic apparatus (NuMA) networks, spectrins, titin, 'unconventional' polymers of actin and at least ten different myosin and kinesin motors. These elements constitute a poorly understood 'network of networks' that dynamically reorganizes during mitosis and is responsible for genome organization and integrity. PMID- 21971045 TI - Phosphatidylserine binding is essential for plasma membrane recruitment and signaling function of 3-phosphoinositide-dependent kinase-1. AB - 3-Phosphoinositide-dependent kinase-1 (PDK1) is a ubiquitously expressed serine/threonine kinase that functions downstream of phosphoinositide 3-kinase. Although binding of 3'-phosphoinositides, phosphatidylinositol 3,4,5 trisphosphate and phosphatidylinositol 3,4-bisphosphate, to the pleckstrin homology (PH) domain of PDK1 is known to be essential for its interaction with and activation of downstream kinases, the mechanism by which PDK1 is recruited to the plasma membrane remains controversial. Our surface plasmon resonance analysis of the PDK1 PH domain and selected mutants shows that the PH domain specifically binds phosphatidylserine using a site that is separate from the canonical phosphoinositide-binding site. Further cell studies show that this specific phosphatidylserine binding is important for the plasma membrane localization and signaling function of PDK1. PMID- 21971046 TI - Protein kinase D3 is a pivotal activator of pathological cardiac hypertrophy by selectively increasing the expression of hypertrophic transcription factors. AB - Fetal cardiac gene reactivation is a hallmark of pathological cardiac hypertrophy (PCH) driven by cardiac transcription factors (TFs) such as nuclear factor of activated T-cells (NFATs). Nuclear import of dephosphorylated NFATs catalyzed by calcineurin (CaN) is a well-established hypertrophic mechanism. Here we report that NFATc4 expression is also up-regulated by newly expressed protein kinase D3 (PKD3) to induce PCH. In both in vitro and in vivo cardiac hypertrophic models, the normally undetectable PKD3 was profoundly up-regulated by isoproterenol followed by overt expression of cardiac TFs including NFATc4, NK family of transcription factor 2.5 (Nkx2.5), GATA4 and myocyte enhancer factor 2 (MEF2). Using gene silencing approaches, we demonstrate PKD3 is required for increasing the expression of NFATc4, Nkx2.5, and GATA4 while PKD1 is required for the increase in MEF2D expression. Upstream induction of PKD3 is driven by nuclear entry of CaN-activated NFATc1 and c3 but not c4. Therefore, PKD3 is a pivotal mediator of the CaN-NFATc1/c3-PKD3-NFATc4 hypertrophic signaling cascade and a potential new drug target for the PCH. PMID- 21971047 TI - 17beta-estradiol represses myogenic differentiation by increasing ubiquitin specific peptidase 19 through estrogen receptor alpha. AB - Skeletal muscles express estrogen receptor (ER) alpha and ERbeta. However, the roles of estrogens acting through the ERs in skeletal muscles remain unclear. The effects of 17beta-estradiol (E2) on myogenesis were studied in C2C12 myoblasts. E2 and an ERalpha-selective agonist propylpyrazole-triol depressed myosin heavy chain (MHC), tropomyosin, and myogenin levels and repressed the fusion of myoblasts into myotubes. ER antagonist ICI 182,780 cancelled E2-repressed myogenesis. E2 induced ubiquitin-specific peptidase 19 (USP19) expression during myogenesis. E2 replacement increased USP19 expression in the gastrocnemius and soleus muscles of ovariectomized mice. Knockdown of USP19 inhibited E2-repressed myogenesis. Mutant forms of USP19 lacking deubiquitinating activity increased MHC and tropomyosin levels. E2 decreased ubiquitinated proteins during myogenesis, and the E2-decreased ubiquitinated proteins were increased by knockdown of USP19. Propylpyrazole-triol increased USP19 expression, and ICI 182,780 inhibited E2 increased USP19 expression. Overexpression of ERalpha or knockdown of ERbeta enhanced the effects of E2 on the levels of USP19, MHC, and tropomyosin, whereas knockdown of ERalpha, overexpression of ERbeta, or an ERbeta-selective agonist diarylpropionitrile abolished their effects. A mutant form of ERalpha that is constitutively localized in the nucleus increased USP19 expression and decreased MHC and tropomyosin expression in the presence of E2. Furthermore, in skeletal muscle satellite cells, E2 inhibited myogenesis and increased USP19 expression, and diarylpropionitrile repressed E2-increased USP19 expression. These results demonstrate that (i) E2 induces USP19 expression through nuclear ERalpha, (ii) increased USP19-mediated deubiquitinating activity represses myogenesis, and (iii) ERbeta inhibits ERalpha-activated USP19 expression. PMID- 21971049 TI - Autotaxin regulates vascular development via multiple lysophosphatidic acid (LPA) receptors in zebrafish. AB - Autotaxin (ATX) is a multifunctional ecto-type phosphodiesterase that converts lysophospholipids, such as lysophosphatidylcholine, to lysophosphatidic acid (LPA) by its lysophospholipase D activity. LPA is a lipid mediator with diverse biological functions, most of which are mediated by G protein-coupled receptors specific to LPA (LPA1-6). Recent studies on ATX knock-out mice revealed that ATX has an essential role in embryonic blood vessel formation. However, the underlying molecular mechanisms remain to be solved. A data base search revealed that ATX and LPA receptors are conserved in wide range of vertebrates from fishes to mammals. Here we analyzed zebrafish ATX (zATX) and LPA receptors both biochemically and functionally. zATX, like mammalian ATX, showed lysophospholipase D activity to produce LPA. In addition, all zebrafish LPA receptors except for LPA5a and LPA5b were found to respond to LPA. Knockdown of zATX in zebrafish embryos by injecting morpholino antisense oligonucleotides (MOs) specific to zATX caused abnormal blood vessel formation, which has not been observed in other morphant embryos or mutants with vascular defects reported previously. In ATX morphant embryos, the segmental arteries sprouted normally from the dorsal aorta but stalled in midcourse, resulting in aberrant vascular connection around the horizontal myoseptum. Similar vascular defects were not observed in embryos in which each single LPA receptor was attenuated by using MOs. Interestingly, similar vascular defects were observed when both LPA1 and LPA4 functions were attenuated by using MOs and/or a selective LPA receptor antagonist, Ki16425. These results demonstrate that the ATX-LPA-LPAR axis is a critical regulator of embryonic vascular development that is conserved in vertebrates. PMID- 21971048 TI - The RNA-binding protein HuR opposes the repression of ERBB-2 gene expression by microRNA miR-331-3p in prostate cancer cells. AB - ERBB-2 overexpression is associated with the development and progression of cancer and mediates its resistance to therapy. It has been suggested that post transcriptional mechanisms control the overexpression of ERBB-2 in prostate cancer (PCa). We recently demonstrated that the 3'-untranslated region (3'-UTR) of ERBB-2 mRNA contains two specific target sites for binding of the microRNA miR 331-3p and that miR-331-3p represses ERBB-2 expression and signaling in PCa cells. Here we investigate a U-rich element situated in close proximity to the distal miR-331-3p target site in the ERBB-2 3'-UTR. Specific binding of HuR to this U-rich element promotes ERBB-2 expression in PCa cells. We show that HuR antagonizes the repressive action of miR-331-3p on its distal ERBB-2 3'-UTR target site. These results support a model in which the interplay between RNA binding proteins and microRNAs controls the post-transcriptional regulation of gene expression and suggest that both HuR and miR-331-3p participate in the overexpression of ERBB-2 observed in some PCas. PMID- 21971051 TI - Monocyte chemotactic protein-induced protein 1 (MCPIP1) suppresses stress granule formation and determines apoptosis under stress. AB - It is unclear how stress granule (SG) formation and cellular apoptosis are coordinately regulated. MCPIP1 (monocyte chemotactic protein-induced protein 1), also known as Zc3h12a, is a critical regulator of the inflammatory response and immune homeostasis. However, the role of MCPIP1 in stress response remains unknown. Here, we report that overexpression of MCPIP1 inhibited the assembly of SGs in response to various stresses. Conversely, MCPIP1-deficient splenocytes developed more SGs even without stress. On the other hand, overexpression of MCPIP1 sensitized RAW 264.7 cells to apoptosis under stress, whereas MCPIP1 deficient cells were resistant to stress-induced apoptosis. Mutagenesis study showed that the ability of MCPIP1 to repress SG formation is dependent on its deubiquitinating activity. Consistently, MCPIP1 negatively regulated stress induced phosphorylation of eIF2alpha and thus released stress-induced inhibition of protein translation. However, MCPIP1 also inhibited 15-deoxy-Delta(12,14) prostaglandin J(2)-induced SG formation, which was reported to be independent of eIF2alpha phosphorylation. Taken together, these results suggest that MCPIP1 coordinates SG formation and apoptosis during cellular stress and may play a critical role in immune homeostasis and resolution of macrophage inflammation. PMID- 21971050 TI - LRP130 protein remodels mitochondria and stimulates fatty acid oxidation. AB - Impaired oxidative phosphorylation (OXPHOS) is implicated in several metabolic disorders. Even though mitochondrial DNA encodes several subunits critical for OXPHOS, the metabolic consequence of activating mitochondrial transcription remains unclear. We show here that LRP130, a protein involved in Leigh syndrome, increases hepatic beta-fatty acid oxidation. Using convergent genetic and biochemical approaches, we demonstrate LRP130 complexes with the mitochondrial RNA polymerase to activate mitochondrial transcription. Activation of mitochondrial transcription is associated with increased OXPHOS activity, increased supercomplexes, and denser cristae, independent of mitochondrial biogenesis. Consistent with increased oxidative phosphorylation, ATP levels are increased in both cells and mouse liver, whereas coupled respiration is increased in cells. We propose activation of mitochondrial transcription remodels mitochondria and enhances oxidative metabolism. PMID- 21971052 TI - Graphene oxide-protected DNA probes for multiplex microRNA analysis in complex biological samples based on a cyclic enzymatic amplification method. AB - Based on graphene oxide-protected DNA probes, we have developed a cyclic enzymatic amplification method for sensitive miRNA detection in complex biological samples. By using the quenching nature of graphene oxide for multiple fluorophores, this method can distinguish highly similar miRNA sequences and detect them simultaneously. PMID- 21971054 TI - Stent design back in the picture: an engineering perspective on longitudinal stent compression. PMID- 21971053 TI - Genome-wide association study of coronary artery disease in the Japanese. AB - A new understanding of the genetic basis of coronary artery disease (CAD) has recently emerged from genome-wide association (GWA) studies of common single nucleotide polymorphisms (SNPs), thus far performed mostly in European-descent populations. To identify novel susceptibility gene variants for CAD and confirm those previously identified mostly in populations of European descent, a multistage GWA study was performed in the Japanese. In the discovery phase, we first genotyped 806 cases and 1337 controls with 451 382 SNP markers and subsequently assessed 34 selected SNPs with direct genotyping (541 additional cases) and in silico comparison (964 healthy controls). In the replication phase, involving 3052 cases and 6335 controls, 12 SNPs were tested; CAD association was replicated and/or verified for 4 (of 12) SNPs from 3 loci: near BRAP and ALDH2 on 12q24 (P=1.6 * 10(-34)), HLA-DQB1 on 6p21 (P=4.7 * 10(-7)), and CDKN2A/B on 9p21 (P=6.1 * 10(-16)). On 12q24, we identified the strongest association signal with the strength of association substantially pronounced for a subgroup of myocardial infarction cases (P=1.4 * 10(-40)). On 6p21, an HLA allele, DQB1(*)0604, could show one of the most prominent association signals in an ~8-Mb interval that encompasses the LTA gene, where an association with myocardial infarction had been reported in another Japanese study. CAD association was also identified at CDKN2A/B, as previously reported in different populations of European descent and Asians. Thus, three loci confirmed in the Japanese GWA study highlight the likely presence of risk alleles with two types of genetic effects - population specific and common - on susceptibility to CAD. PMID- 21971055 TI - Phylogenetic inference rejects sporophyte based classification of the Funariaceae (Bryophyta): rapid radiation suggests rampant homoplasy in sporophyte evolution. AB - The moss family Funariaceae, which includes the model systems Funaria hygrometrica and Physcomitrella patens, comprises 15 genera, of which three accommodate approximately 95% of the 250-400 species. Generic concepts are drawn primarily from patterns in the diversity of morphological complexity of the sporophyte. Phylogenetic inferences from ten loci sampled across the three genomic compartments yield a hypothesis that is incompatible with the current circumscription of two of the speciose genera of the Funariaceae. The single clade, comprising exemplars of Funaria with a compound annulus, is congruent with the systematic concept proposed by Fife (1985). By contrast, Entosthodon and Physcomitrium are resolved as polyphyletic entities, and even the three species of Physcomitrella are confirmed to have diverged from distinct ancestors. Although the backbone relationships within the core clade of the Funariaceae remain unresolved, the polyphyly of these genera withstands alternative hypothesis testing. Consequently, the sporophytic characters that define these lineages are clearly homoplasious suggesting that selective pressures (or their relaxation) are in fact driving the diversification rather than the conservation of sporophytic architecture in the Funariaceae. PMID- 21971056 TI - Multilocus phylogeny of Crenicichla (Teleostei: Cichlidae), with biogeography of the C. lacustris group: species flocks as a model for sympatric speciation in rivers. AB - First multilocus analysis of the largest Neotropical cichlid genus Crenicichla combining mitochondrial (cytb, ND2, 16S) and nuclear (S7 intron 1) genes and comprising 602 sequences of 169 specimens yields a robust phylogenetic hypothesis. The best marker in the combined analysis is the ND2 gene which contributes throughout the whole range of hierarchical levels in the tree and shows weak effects of saturation at the 3rd codon position. The 16S locus exerts almost no influence on the inferred phylogeny. The nuclear S7 intron 1 resolves mainly deeper nodes. Crenicichla is split into two main clades: (1) Teleocichla, the Crenicichla wallacii group, and the Crenicichla lugubris-Crenicichla saxatilis groups ("the TWLuS clade"); (2) the Crenicichla reticulata group and the Crenicichla lacustris group-Crenicichla macrophthalma ("the RMLa clade"). Our study confirms the monophyly of the C. lacustris species group with very high support. The biogeographic reconstruction of the C. lacustris group using dispersal-vicariance analysis underlines the importance of ancient barriers between the middle and upper Parana River (the Guaira Falls) and between the middle and upper Uruguay River (the Mocona Falls). Our phylogeny recovers two endemic species flocks within the C. lacustris group, the Crenicichla missioneira species flock and the herein discovered Crenicichla mandelburgeri species flock from the Uruguay and Parana/Iguazu Rivers, respectively. We discuss putative sympatric diversification of trophic traits (morphology of jaws and lips, dentition) and propose these species flocks as models for studying sympatric speciation in complex riverine systems. The possible role of hybridization as a mechanism of speciation is mentioned with a recorded example (Crenicichla scottii). PMID- 21971057 TI - Join the cone of critics. PMID- 21971058 TI - Technical tips for (dry) arthroscopic reduction and internal fixation of distal radius fractures. AB - Contrary to general belief, arthroscopic assisted reduction in distal radius fractures can be done in an expeditious manner and with minimal consumption of operating room resources. This article presents the steps for a pleasant arthroscopic experience in detail. The technique proposed combines the benefits of rigid fixation with volar locking plates (for the extra-articular component) and arthroscopic control of the reduction (for the articular component). It is important that the operation be carried out using the dry arthroscopic technique. However, arthroscopy is just an addition to conventional methods. Thorough knowledge of and facility with classic techniques of distal radius fracture treatment is essential for a good result. PMID- 21971059 TI - Surgical hand antisepsis for the hand surgeon. PMID- 21971060 TI - Update on advances in upper extremity prosthetics. AB - Upper extremity amputations are common. Fortunately, most of these involve loss of only a finger or portion thereof. Hand and upper limb surgeons are best suited to lead the team and help these patients following these injuries. Proximal amputations can be devastating for the patient, but recent prosthetic advances have helped many patients lead a better life and, often, return to activities they were involved in before their amputation. The purpose of this article is to review the current prostheses available for upper extremity amputees. PMID- 21971061 TI - Management of upper limb amputations. AB - Acquired upper extremity amputations beyond the finger can have substantial physical, psychological, social, and economic consequences for the patient. The hand surgeon is one of a team of specialists in the care of these patients, but the surgeon plays a critical role in the surgical management of these wounds. The execution of a successful amputation at each level of the limb allows maximum use of the residual extremity, with or without a prosthesis, and minimizes the known complications of these injuries. This article reviews current surgical options in performing and managing upper extremity amputations proximal to the finger. PMID- 21971063 TI - Electrochemical charge transfer mediated by metal nanoparticles and quantum dots. AB - Electron transfer processes mediated by nanostructured materials assembled at electrode surfaces underpin fundamental processes in novel electrochemical sensors, light energy conversion systems and molecular electronics. Functionalisation of electrode surfaces with hierarchical architectures incorporating self-assembling molecular systems and materials, such as metal nanostructures, quantum dots, carbon nanotubes, graphene or biomolecules have been intensively studied over the last 20 years. Important steps have been made towards the rationalisation of the charge transfer dynamics from redox species in solution across molecular self-assembling systems to electrode surfaces. For instance, a unified picture has emerged describing the factors which determine the rate constant for electron transfer processes across rigid self-assembling molecular barriers. An increasing bulk of evidence has recently shown that the incorporation of nanomaterials into self-assembling monolayers leads to an entirely different electrochemical behaviour. This perspective rationalises some of the key observations associated with nanoparticle mediated charge transfer, such as the apparent distance independent charge transfer resistance observed for redox species in solution. This behaviour only manifests itself clearly in the case where the probability of direct charge transfer from the redox probe to the electrode is strongly attenuated by self-assembling molecular barriers. Here we will highlight specific issues concerning self-assembled monolayers as blocking barriers prior to discussing the effect of nanoparticles on the electrochemical response of the system. Selected examples will provide conclusive evidence that the extent of charge transfer mediation is determined by the overlap between the density of states of the nanostructures and the energy levels of redox species in solution. Only in the case where a strong overlap exists between the energy levels of the two components, the nanostructures behave as "electron launchers", allowing efficient charge transfer across insulating molecular layers. PMID- 21971062 TI - Development of an efficient in vitro transcription system for bloodstream form Trypanosoma brucei reveals life cycle-independent functionality of class I transcription factor A. AB - Trypanosomatid parasites possess extremely divergent transcription factors whose identification typically relied on biochemical, structural and functional analyses because they could not be identified by standard sequence analysis. For example, subunits of the Trypanosoma brucei mediator and class I transcription factor A (CITFA) have no sequence resemblance to putative counterparts in higher eukaryotes. Therefore, homologous in vitro transcription systems have been crucial in evaluating the transcriptional roles of T. brucei proteins but so far such systems have been restricted to the insect-stage, procyclic form (PF) of the parasite. Here, we report the development of a homologous system for the mammalian-infective, bloodstream form (BF) of T. brucei which supports accurately initiated transcription from three different RNA polymerase (pol) I promoters as well as from the RNA pol II-recruiting spliced leader RNA gene promoter. The system is based on a small scale extract preparation procedure which accommodates the low cell densities obtainable in BF culture. BF and PF systems behave surprisingly similar and we show that the CITFA complex purified from procyclic extract is fully functional in the BF system indicating that the transcriptional machinery in general is equivalent in both life cycle stages. A notable difference, however, was observed with the RNA pol I-recruiting GPEET procyclin promoter whose reduced promoter strength and increased sensitivity to manganese ions in the BF system suggests the presence of a specific transcriptional activator in the PF system. PMID- 21971064 TI - Stability and magnetorheological behaviour of magnetic fluids based on ionic liquids. AB - This paper reports the preparation of magnetic fluids consisting of magnetite nanoparticles dispersed in an ionic liquid. Different additives were used in order to stabilize the fluids. Colloidal stability was checked by magnetic sedimentation, centrifugation and direct observation. The results of these tests showed that a true ferrofluid was only obtained when the nanoparticles were coated with a layer of surfactant compatible with the ionic liquid. These experiments also showed that stability could not be reached just by electrostatic repulsion. The conclusions of the stability tests were confirmed by calculations of the interparticle energies of interaction. The rheological behaviour of the magnetic fluids upon magnetic field application was also investigated. The experimental magnetoviscous response was fitted by a microstructural model. The model considered that the fluids consisted of two populations of particles, one with a magnetic core diameter of 9 nm, and another with a larger diameter. Upon field application chain-like structures are supposed to be induced. According to estimations particles of 9 nm are too small to aggregate upon field application. The results of the calculations showed that the intensity of the magnetoviscous response depends on the concentration and size of the large particles, and on the thickness of the surfactant layers. PMID- 21971067 TI - The regional specificity of rapid actions of cocaine. PMID- 21971068 TI - Sensory systems: Charting vomeronasal receptor function. PMID- 21971069 TI - Pain: A prickly solution? PMID- 21971065 TI - Opiate versus psychostimulant addiction: the differences do matter. AB - The publication of the psychomotor stimulant theory of addiction in 1987 and the finding that addictive drugs increase dopamine concentrations in the rat mesolimbic system in 1988 have led to a predominance of psychobiological theories that consider addiction to opiates and addiction to psychostimulants as essentially identical phenomena. Indeed, current theories of addiction - hedonic allostasis, incentive sensitization, aberrant learning and frontostriatal dysfunction - all argue for a unitary account of drug addiction. This view is challenged by behavioural, cognitive and neurobiological findings in laboratory animals and humans. Here, we argue that opiate addiction and psychostimulant addiction are behaviourally and neurobiologically distinct and that the differences have important implications for addiction treatment, addiction theories and future research. PMID- 21971070 TI - Enhancing transgenic pea (Pisum sativum L.) resistance against fungal diseases through stacking of two antifungal genes (chitinase and glucanase). AB - One way of enhancing and broadening resistance of plants to different biotic and abiotic stresses is to combine transgenes expressing several genes into a single line. This can be done using different strategies such as crossing, single vector with multiple genes, co-transformation, sequential transformation and IRES elements. In the present study conventional crossing method was used. Parental transgenic lines transformed via Agrobacterium tumefasciens-mediated gene transformation with pGreenII binary vector harbouring a bar gene as selectable marker in combination with the family 19 chitinase gene from Streptomyces olivaceoviridis for one line and 1,3-beta-glucanase from barley (Hordeum vulgare) for the other line were used for crossing. Both chitinase and glucanase genes were cloned into pGreenII vector under the control of the constitutive double 35S promoter from cauliflower mosaic virus. Progenies expressing the two genes were characterised at the molecular level using PCR, RT-PCR and Southern blot analysis, as well as segregation and stability studies of the respective expression levels. Leaf paint assay was used as functional test for herbicide resistant gene. Stable inheritance of the antifungal genes in the transgenic plants was demonstrated. The synergistic effect of crossed plants was tested using in vitro assay which shows higher inhibition of spore germination. PMID- 21971072 TI - Cardiac myosin binding protein-C is a potential diagnostic biomarker for myocardial infarction. AB - Cardiac myosin binding protein-C (cMyBP-C) is a thick filament assembly protein that stabilizes sarcomeric structure and regulates cardiac function; however, the profile of cMyBP-C degradation after myocardial infarction (MI) is unknown. We hypothesized that cMyBP-C is sensitive to proteolysis and is specifically increased in the bloodstream post-MI in rats and humans. Under these circumstances, elevated levels of degraded cMyBP-C could be used as a diagnostic tool to confirm MI. To test this hypothesis, we first established that cMyBP-C dephosphorylation is directly associated with increased degradation of this myofilament protein, leading to its release in vitro. Using neonatal rat ventricular cardiomyocytes in vitro, we were able to correlate the induction of hypoxic stress with increased cMyBP-C dephosphorylation, degradation, and the specific release of N'-fragments. Next, to define the proteolytic pattern of cMyBP-C post-MI, the left anterior descending coronary artery was ligated in adult male rats. Degradation of cMyBP-C was confirmed by a reduction in total cMyBP-C and the presence of degradation products in the infarct tissue. Phosphorylation levels of cMyBP-C were greatly reduced in ischemic areas of the MI heart compared to non-ischemic regions and sham control hearts. Post-MI plasma samples from these rats, as well as humans, were assayed for cMyBP-C and its fragments by sandwich ELISA and immunoprecipitation analyses. Results showed significantly elevated levels of cMyBP-C in the plasma of all post-MI samples. Overall, this study suggests that cMyBP-C is an easily releasable myofilament protein that is dephosphorylated, degraded and released into the circulation post MI. The presence of elevated levels of cMyBP-C in the blood provides a promising novel biomarker able to accurately rule in MI, thus aiding in the further assessment of ischemic heart disease. PMID- 21971073 TI - Peri-interventional coronary vasomotion. AB - A percutaneous coronary intervention (PCI) is a unique condition to study the effects of ischemia and reperfusion in patients with severe coronary atherosclerosis when coronary vasomotor function is compromised by loss of endothelial and autoregulatory vasodilation. We studied the effects of intracoronary non-selective alpha-, as well as selective alpha(1)- and alpha(2) blockade in counteracting the observed vasoconstriction in patients with stable and unstable angina and in patients with acute myocardial infarction. Coronary vasoconstriction in our studies was a diffuse phenomenon and involved not only the culprit lesion but also vessels with angiographically not visible plaques. Post-PCI vasoconstriction was reflected by increased coronary vascular resistance and associated with decreased LV-function. alpha (1)-Blockade with urapidil dilated epicardial coronary arteries, improved coronary flow reserve and counteracted LV dysfunction. Non-selective alpha-blockade with phentolamine induced epicardial and microvascular dilation, while selective alpha(2)-blockade with yohimbine had only minor vasodilator and functional effects. Intracoronary alpha-blockade also attenuated the no-reflow phenomenon following primary PCI. This article is part of a Special Issue entitled "Coronary Blood Flow". PMID- 21971075 TI - Small changes can make a big difference - microRNA regulation of cardiac hypertrophy. AB - Cardiac hypertrophy is a thickening of the heart muscle that results in enlargement of the ventricles, which is the primary response of the myocardium to stress or mechanical overload. Cardiac pathological and physiological hemodynamic overload causes enhanced protein synthesis, sarcomeric reorganization and density, and increased cardiomyocyte size, all culminating into structural remodeling of the heart. With clinical evidence demonstrating that sustained hypertrophy is a key risk factor in heart failure development, much effort is centered on the identification of signals and pathways leading to pathological hypertrophy for future rational drug design in heart failure therapy. A wide variety of studies indicate that individual microRNAs exhibit altered expression profiles under experimental and clinical conditions of cardiac hypertrophy and heart failure. Here we review the recent literature, illustrating how single microRNAs regulate cardiac hypertrophy by classifying them by their prohypertrophic or antihypertrophic properties and their specific effects on intracellular signaling cascades, ubiquitination processes, sarcomere composition and by promoting inter-cellular communication. PMID- 21971074 TI - Ablation of p21-activated kinase-1 in mice promotes isoproterenol-induced cardiac hypertrophy in association with activation of Erk1/2 and inhibition of protein phosphatase 2A. AB - Earlier investigations in our lab indicated an anti-adrenergic effect induced by activation of p21-activated kinase (Pak-1) and protein phosphatase 2A (PP2A). Our objective was to test the hypothesis that Pak-1/PP2A is a signaling cascade controlling stress-induced cardiac growth. We determined the effects of ablation of the Pak-1 gene on the response of the myocardium to chronic stress of isoproterenol (ISO) administration. Wild-type (WT) and Pak-1-knockout (Pak-1-KO) mice were randomized into six groups to receive either ISO, saline (CTRL), or ISO and FR180204, a selective inhibitor of Erk1/2. Echocardiography revealed that hearts of the Pak-1-KO/ISO group had increased LV fractional shortening, reduced LV chamber volume in diastole and systole, increased cardiac hypertrophy, and enhanced transmitral early filling deceleration time, compared to all other groups. The changes were associated with an increase in relative Erk1/2 activation in Pak-1-KO/ISO mice versus all other groups. ISO-induced cardiac hypertrophy and Erk1/2 activation in Pak-1-KO/ISO were attenuated when the selective Erk1/2 inhibitor FR180204 was administered. Immunoprecipitation showed an association between Pak-1, PP2A, and Erk1/2. Cardiac myocytes infected with an adenoviral vector expressing constitutively active Pak-1 showed a repression of Erk1/2 activation. p38 MAPK phosphorylation was decreased in Pak-1-KO/ISO and Pak 1-KO/CTRL mice compared to WT. Levels of phosphorylated PP2A were increased in ISO-treated Pak-1-KO mice, indicating reduced phosphatase activity. Maximum Ca(2+)-activated tension in detergent-extracted bundles of papillary fibers from ISO-treated Pak-1-KO mice was higher than in all other groups. Analysis of cTnI phosphorylation indicated that compared to WT, ISO-induced phosphorylation of cTnI was blunted in Pak-1-KO mice. Active Pak-1 is a natural inhibitor of Erk1/2 and a novel anti-hypertrophic signaling molecule upstream of PP2A. PMID- 21971076 TI - Enterobacter endophthalmitis: clinicomicrobiologic profile and outcomes. AB - PURPOSE: To report the clinical presentations, antibiotic sensitivities, management, and outcomes of Enterobacter endophthalmitis. METHODS: This is a retrospective, consecutive, noncomparative, interventional case series. The medical records of culture-proven Enterobacter endophthalmitis cases from the endophthalmitis registry between January 1995 and March 2006 were reviewed. RESULTS: Enterobacter was the causative agent in 36 culture-proven cases. The causative event was cataract surgery in 11 and trauma in 25 patients. The presenting visual acuity was light perception in 26 eyes (72.2%). Polymicrobial infection was detected in 7 patients (19.4%). Enterobacter organisms were most sensitive to ciprofloxacin (n = 34; 94%), followed by amikacin (n = 31; 86%) and ceftazidime (n = 28; 78%). In postoperative endophthalmitis, final visual outcome of >=20/200 was achieved in 3 patients (27%) and of >=5/200 in 5 patients (45%). The eyes became phthisical in 3 patients (27%) and evisceration was carried out in 1 patient. In posttraumatic endophthalmitis, final visual outcome of >=20/200 was achieved in 5 patients (20%) and of >=5/200 in 7 patients (28%). The eyes of 11 patients (44%) became phthisical and evisceration was carried out in 1 patient. CONCLUSION: Enterobacter organisms are mostly susceptible to ciprofloxacin, amikacin, and ceftazidime. Despite this coverage, the visual outcome is often poor. PMID- 21971077 TI - Long-term safety, high-resolution imaging, and tissue temperature modeling of subvisible diode micropulse photocoagulation for retinovascular macular edema. AB - PURPOSE: To determine the long-term safety of high-density subvisible diode micropulse photocoagulation (810 nm), compare the clinical findings with computational modeling of tissue hyperthermia and to report results for a subset of eyes treated for diabetic macular edema (ME) documented pre- and postoperatively by spectral-domain optical coherence tomography. METHOD: All eyes treated for ME from diabetic retinopathy (diabetic ME) and branch retinal vein occlusion between April 2000 and January 2010 were reviewed for subvisible diode micropulse laser-induced retinal damage. Therapeutic outcomes were reviewed for a subgroup treated for diabetic ME with pre- and postoperative spectral-domain optical coherence tomography. Laser-induced retinal thermal effects were modeled computationally using Arrhenius formalism. RESULTS: A total of 252 eyes (212 diabetic ME, 40 branch retinal vein occlusion) of 181 patients qualified. None of the 168 eyes treated at irradiance <350 W/cm2 and 7 of 84 eyes at >= 590 W/cm2 had retinal damage (P = 0.0001) (follow-up 3-120 months, median, 47). Sixty-two eyes of 48 patients treated for diabetic ME with pre- and postoperative spectral domain optical coherence tomography with median 12 months follow-up had no retinal injury by infrared, red-free, or fundus autofluorescence photos; fluorescein angiography or indocyanine green angiography; or spectral-domain optical coherence tomography. Central foveal thickness (P = 0.04) and maximum macular thickness decreased (P < 0.0001). Modeling of retinal hyperthermia demonstrates that the sublethal clinical regimen corresponds to Arrhenius integral >0.05, while damage is likely to occur if it exceeds 1. CONCLUSION: Subvisible diode micropulse can effectively treat retinovascular ME without laser induced retinal damage, consistent with Arrhenius modeling of pulsed hyperthermia. PMID- 21971078 TI - Significant differences in gene expression of GABA receptors in peripheral blood leukocytes of migraineurs. AB - Migraine is a debilitating neurovascular disorder, with a substantial genetic component. The exact cause of a migraine attack is unknown; however cortical hyperexcitability is thought to play a role. As Gamma-aminobutyric Acid (GABA) is the major inhibitory neurotransmitter in the brain, malfunctioning of this system may be a cause of the hyperexcitability. To date, there has been limited research examining the gene expression or genetics of GABA receptors in relation to migraine. The aim of our study was to determine if GABA receptors play a role in migraine by investigating their gene expression using profile in migraine affected individuals and non-affected controls by Q-PCR. Gene expression of GABA(A) receptor subunit isoforms (GABRA3, GABRB3, GABRQ) and GABA(B) receptor 2 (GABBR2) was quantified in mRNA obtained from peripheral blood leukocytes from 28 migraine subjects and 22 healthy control subjects. Analysis of results showed that two of the tested genes, GABRA3 and GABBR2, were significantly down regulated in migraineurs (P=0.018; P=0.017), compared to controls. Results from the other tested genes did not show significant gene expression variation. The results indicate that there may be specific GABA receptor gene expression variation in migraine, particularly involving the GABRA3 and GABBR2 genes. This study also identifies GABRA3 and GABBR2 as potential biomarkers to select migraineurs that may be more responsive to GABA agonists with future investigations in this area warranted. PMID- 21971079 TI - A SiPM-based isotropic-3D PET detector X'tal cube with a three-dimensional array of 1 mm(3) crystals. AB - We are developing a novel, general purpose isotropic-3D PET detector X'tal cube which has high spatial resolution in all three dimensions. The research challenge for this detector is implementing effective detection of scintillation photons by covering six faces of a segmented crystal block with silicon photomultipliers (SiPMs). In this paper, we developed the second prototype of the X'tal cube for a proof-of-concept. We aimed at realizing an ultimate detector with 1.0 mm(3) cubic crystals, in contrast to our previous development using 3.0 mm(3) cubic crystals. The crystal block was composed of a 16 * 16 * 16 array of lutetium gadolinium oxyorthosilicate (LGSO) crystals 0.993 * 0.993 * 0.993 mm(3) in size. The crystals were optically glued together without inserting any reflector inside and 96 multi-pixel photon counters (MPPCs, S10931-50P, i.e. six faces each with a 4 * 4 array of MPPCs), each having a sensitive area of 3.0 * 3.0 mm(2), were optically coupled to the surfaces of the crystal block. Almost all 4096 crystals were identified through Anger-type calculation due to the finely adjusted reflector sheets inserted between the crystal block and light guides. The reflector sheets, which formed a belt of 0.5 mm width, were placed to cover half of the crystals of the second rows from the edges in order to improve identification performance of the crystals near the edges. Energy resolution of 12.7% was obtained at 511 keV with almost uniform light output for all crystal segments thanks to the effective detection of the scintillation photons. PMID- 21971080 TI - Characterization of acetonitrile-tolerant marine bacterium Exiguobacterium sp. SBH81 and its tolerance mechanism. AB - A Gram-positive marine bacterium, Exiguobacterium sp. SBH81, was isolated as a hydrophilic organic-solvent tolerant bacterium, and exhibited high tolerance to various types of toxic hydrophilic organic solvents, including acetonitrile, at relatively high concentrations (up to 6% [v/v]) under the growing conditions. Investigation of its tolerance mechanisms illustrated that it does not rely on solvent inactivation processes or modification of cell surface characteristics, but rather, increase of the cell size lowers solvent partitioning into cells and the extrusion of solvents through the efflux system. A test using efflux pump inhibitors suggested that secondary transporters, i.e. resistance nodulation cell division (RND) and the multidrug and toxic compound extrusion (MATE) family, are involved in acetonitrile tolerance in this strain. In addition, its acetonitrile tolerance ability could be stably and significantly enhanced by repetitive growth in the presence of toxic acetonitrile. The marked acetonitrile tolerance of Exiguobacterium sp. SBH81 indicates its potential use as a host for biotechnological fermentation processes as well as bioremediation. PMID- 21971082 TI - Effect of lyophilized powder made from enzymolyzed honeybee larvae on tinnitus related symptoms, hearing levels, and hypothalamus-pituitary-adrenal axis-related hormones. AB - OBJECTIVES: Tinnitus interferes with sleep and concentration which is associated with depression; however, no drug has been effective in treating tinnitus. Our purpose is to evaluate our hypothesis that the treatment with lyophilized powder of enzymolyzed honeybee larvae as a complementary medicine may provide a therapeutic effect on tinnitus-related symptoms. DESIGN: Sixty tinnitus sufferers participated in a randomized double-blind placebo-controlled trial using the lyophilized powder of enzymolyzed honeybee larvae or a placebo. The Tinnitus Handicap Inventory, a visual analog scale to rate the severity of tinnitus, hearing levels, and hypothalamus-pituitary-adrenal axis-related hormones drawn early in the morning were measured upon entry into the study and after 12 wk of follow-up. RESULTS: The lyophilized powder of enzymolyzed honeybee larvae was not superior to placebo with regard to the total score on the Tinnitus Handicap Inventory and the visual analog scale. However, subjects in the honeybee larvae group showed significant improvements in some items about depression associated with tinnitus, whereas subjects in the placebo group showed no improvement in any items. The honeybee larvae group showed significant improvements in the hearing levels at 2 and 4 kHz in the audiogram of the better ear. The intervention of the lyophilized powder of enzymolyzed honeybee larvae was associated with lower serum cortisol levels, serum prolactin levels, and cortisol/dehydroepiandrosterone sulfate ratios. The ratios in the placebo group significantly were increased. CONCLUSIONS: Our results suggest that the lyophilized powder of enzymolyzed honeybee larvae represents an effective complementary medicine to alleviate depression associated with tinnitus by regulating the activity of the hypothalamus-pituitary-adrenal axis. PMID- 21971083 TI - Fathers' coping resources and children's socioemotional adjustment among children with learning disabilities. AB - This study examined a cumulative model of vulnerability and protective factors at the individual level (children's attachment relationships with father and children's sense of coherence) and at the family level as manifested by fathers' coping resources (fathers' sense of coherence, fathers' active and avoidant coping strategies) in helping to explain differences in socioemotional and behavioral adjustment among children at the age 8 to 12 years with learning disabilities (LD) and or with typical development. The sample included 205 father child dyads: 107 fathers and their children having LD and 98 fathers and their children with typical development, from the same public elementary schools. Preliminary analyses indicated significant group differences on all the children's measures as well as on fathers' avoidant coping strategies. Path analysis examined the multidimensional risk model for the LD and non-LD groups. The study found a high fit between the theoretical model and the empirical findings as well as a different pattern of relationship between the model's components for the two populations studied. Discussion focuses on understanding the unique value of vulnerability and protective factors at the individual and family levels on children's well-adjusted functioning. PMID- 21971081 TI - Variability of prokaryotic community structure in a drinking water reservoir (Marathonas, Greece). AB - The structure of the Bacteria and Archaea community in a large drinking water reservoir (Marathonas, Greece; MR) was investigated in October 2007 and September 2008, using 16S rRNA gene clone libraries. The bacterial communities were more diverse than archaeal communities (Shannon diversity index H' 0.81-3.28 and 1.36 1.77, respectively). The overall bacterial community composition was comparable to bacterioplankton community described in other freshwater habitats. Within the Bacteria, Betaproteobacteria dominated, while representatives of Alpha-, Gamma- and Deltaproteobacteria also occurred. Other important phyla were Actinobacteria and Bacteroidetes, while representatives of Acidobacteria, Cyanobacteria, Chloroflexi, Planctomycetes and Verrucomicrobia were also retrieved. Several phylotypes in Alpha- and Betaproteobacteria and Bacteroidetes were related to bacteria capable of cyanotoxin degradation and with aromatic compounds/iron oxidizers or polymer degraders. Euryarchaeota dominated (60.5%) the Archaea community mostly with phylotypes related to Methanobacteriales and Methanosarcinales. Among the Thaumarchaeota, the two most abundant phylotypes were affiliated (97% similarity) with the only cultivated mesophilic thaumarchaeote of marine origin, Nitrosopumilus maritimus. Temporal and spatial comparison of the prokaryotic community structure revealed that three of the most abundant prokaryotic phylotypes, belonging to Actinobacteria, were recovered from all sites both years, suggesting that these Actinobacteria could be important key players in MR ecosystem functioning. PMID- 21971084 TI - Metacognitive strategy use of eighth-grade students with and without learning disabilities during mathematical problem solving: a think-aloud analysis. AB - The purpose of the study was to investigate the metacognitive abilities of students with LD as they engage in math problem solving and to determine processing differences between these students and their low- and average achieving peers (n = 73). Students thought out loud as they solved three math problems of increasing difficulty. Protocols were coded and analyzed to determine frequency of cognitive verbalizations and productive and nonproductive metacognitive verbalizations. Results indicated different patterns of metacognitive activity for ability groups when type of metacognitive verbalization and problem difficulty were considered. Implications for instruction are discussed. PMID- 21971087 TI - One-pot regioselective synthesis and X-ray crystal structure of a stable [60]fullerene trisadduct with the e(edge),e(face),trans-1 addition pattern. AB - The Bingel functionalisation of C(60) with a structurally novel tether equipped with three reactive malonate groups afforded a C(2v)-symmetrical e(edge),e(face),trans-1 trisadduct in a complete regioselective manner and in an excellent yield of 65%. The [60]fullerene trisadduct showed pronounced ability to crystallise and gave X-ray quality single crystals for analysis. PMID- 21971086 TI - Distinct role of Mediator tail module in regulation of SAGA-dependent, TATA containing genes in yeast. AB - The evolutionarily conserved Mediator complex is required for transcription of nearly all RNA Pol II-dependent promoters, with the tail module serving to recruit Mediator to active promoters in current models. However, transcriptional dependence on tail module subunits varies in a gene-specific manner, and the generality of the tail module requirement for transcriptional activation has not been explored. Here, we show that tail module subunits function redundantly to recruit Mediator to promoters in yeast, and transcriptome analysis shows stronger effects on genome-wide expression in a double-tail subunit deletion mutant than in single-subunit deletion mutants. Unexpectedly, TATA-containing and SAGA dependent genes were much more affected by impairment of tail module function than were TFIID-dependent genes. Consistent with this finding, Mediator and preinitiation complex association with SAGA-dependent promoters is substantially reduced in gal11/med15Delta med3Delta yeast, whereas association of TBP, Pol II, and other Mediator modules with TFIID-dependent genes is largely independent of the tail module. Thus, we have identified a connection between the Mediator tail module and the division of promoter dependence between TFIID and SAGA. PMID- 21971085 TI - OCRL controls trafficking through early endosomes via PtdIns4,5P2-dependent regulation of endosomal actin. AB - Mutations in the phosphatidylinositol 4,5-bisphosphate (PtdIns4,5P(2)) 5 phosphatase OCRL cause Lowe syndrome, which is characterised by congenital cataracts, central hypotonia, and renal proximal tubular dysfunction. Previous studies have shown that OCRL interacts with components of the endosomal machinery; however, its role in endocytosis, and thus the pathogenic mechanisms of Lowe syndrome, have remained elusive. Here, we show that via its 5-phosphatase activity, OCRL controls early endosome (EE) function. OCRL depletion impairs the recycling of multiple classes of receptors, including megalin (which mediates protein reabsorption in the kidney) that are retained in engorged EEs. These trafficking defects are caused by ectopic accumulation of PtdIns4,5P(2) in EEs, which in turn induces an N-WASP-dependent increase in endosomal F-actin. Our data provide a molecular explanation for renal proximal tubular dysfunction in Lowe syndrome and highlight that tight control of PtdIns4,5P(2) and F-actin at the EEs is essential for exporting cargoes that transit this compartment. PMID- 21971088 TI - Small-molecule ligands strongly affect the Forster resonance energy transfer between a quantum dot and a fluorescent protein. AB - We report herein the study of Forster resonance energy transfer (FRET) between a CdSe/ZnS core/shell quantum dot (QD) capped with three different small-molecule ligands, 3-mercaptopropionic acid (MPA), glutathione (GSH), and dihydrolipoic acid (DHLA), and a hexa-histidine (His(6))-tagged fluorescent protein, mCherry (FP). The Forster radius (R(0)) and the corresponding donor-acceptor distances (r) for each of the QD-FP FRET systems were evaluated by using the Forster dipole dipole interaction formula. Interestingly, both the FRET efficiency (E) and r were found to be strongly dependent on the capping small-molecule ligands on the QD surface, where E ~ 85% was obtained at a FP:QD copy number of 2:1 for the MPA capped QD, while that for the DHLA capped QD was <25% under the same conditions. A molecular model was proposed to explain the possible reasons behind these observations. The dissociation constants (K(d)s) and kinetics of the self assembled QD-FP systems were also evaluated. Results show that the QD-FP self assembly process is fast (completes in minutes at low nM concentrations), strong (with K(d) ~ 1 nM) and positively cooperative (with the Hill coefficient n > 1), suggesting that the QD-His(6)-tagged biomolecule self-assembly is a facile, effective approach for making compact QD-bioconjugates which may have a wide range of sensing and biomedical applications. PMID- 21971089 TI - KIT mutations in Russian patients with mucosal melanoma. AB - A single institution series of 48 mucosal melanomas (MMs) has been analyzed for the presence of KIT mutations using high-resolution melting and sequencing of abnormally melted DNA fragments. The analysis of exons 9, 11, 13, and 17 has revealed eight of 48 (17%) nonsynonymous alterations, including zero of seven head and neck, six of 24 anorectal, one of 15 genitourinary, one of one gastric, and zero of one mediastinal MMs. Seven of these mutations were potentially associated with the tumor sensitivity to KIT tyrosine kinase inhibitors. One tumor harbored somatically acquired silent nucleotide substitution c.1383A>G (T461T). This study adds to the evidence that a substantial portion of MMs carry a therapeutically relevant mutation in the KIT oncogene. PMID- 21971090 TI - Invited commentary. PMID- 21971092 TI - Utility of duplex ultrasound in detecting and grading de novo femoropopliteal lesions. AB - BACKGROUND: Digital subtraction angiography (DSA) is the gold standard for diagnosing lower extremity (LE) arterial lesions. However, duplex ultrasound (DUS) is a widely used, safe, and noninvasive method of detecting LE lesions. The purpose of this study was to establish DUS criteria for detecting and grading de novo stenotic lesions in the femoropopliteal arterial segment. METHODS: A prospective database was established including all patients who underwent LE endovascular interventions between 2004 and 2009. Patients with de novo stenotic lesions in the femoropopliteal segment were selected. DUS and DSA data pairs <=30 days apart were analyzed. Peak systolic velocity (PSV; cm/s), velocity ratio (Vr), and DSA stenosis were noted. Linear regression and receiver operator characteristic (ROC) curves were used. RESULTS: Two hundred seventy-five lesions in 200 patients were analyzed. Indications were claudication (50.5%), rest pain (12.5%), and tissue loss (37.0%). Mean time interval between DUS and DSA was 24 days. Both PSV (R = .80, R(2) = .641; P < .001) and Vr (R = .73, R(2) = .546; P < .001) showed strong correlation with the degree of angiographic stenosis. ROC analysis showed that to detect >=70% stenosis, a PSV of 200 cm/s had 89.2% sensitivity and 89.7% specificity, and a Vr of 2.0 had 88.7% sensitivity and 90.2% specificity. Similarly, to differentiate between <50% and >=50% stenosis, PSV of 150 cm/s and Vr of 1.5 were highly specific and predictive. Combining PSV 200 cm/s and Vr 2.0 for >=70% stenosis gave 79.0% sensitivity, 99.0% specificity, 99.0% positive predictive value, and 85.0% negative predictive value. CONCLUSION: DUS shows a strong agreement with angiography and has good accuracy in detecting femoropopliteal lesions. We propose DUS criteria of PSV 200 cm/s and Vr 2.0 to differentiate between <70% and >=70% de novo stenosis in the femoropopliteal arterial segment. PMID- 21971093 TI - A systematic review of lower extremity arterial revascularization economic analyses. AB - OBJECTIVE: Economic evaluation remains an understudied aspect of lower extremity vascular reconstructions. This study reviewed the economic-based literature with respect to open and endovascular treatment of peripheral arterial disease. METHODS: This systematic review included economic analyses of open and endovascular treatment of lower extremity peripheral arterial disease, including claudication and critical limb ischemia. Studies were categorized as model-based, cost-consequences, or econometric cost-analyses. Clinical, financial, and time based outcomes were examined. RESULTS: From a candidate list of 1351 studies, 19 were appropriate for the review, comprising 3 model-based, 12 cost-consequence, and 4 cost-analyses. Because of the small numbers, claudication and critical limb ischemia studies were analyzed together. There was a trend favoring initial cost savings with endovascular therapy. Whether this benefit is sustained over time is unknown. We were prevented from drawing cost-efficacy inferences because of a noted lack of standardized patient-centric outcomes, longitudinal data, and reintervention data. CONCLUSIONS: The existing lower extremity arterial revascularization economic literature is inadequate for drawing cost-efficacy conclusions and cannot inform guidelines for open vs endovascular treatment. Overcoming this limitation will require the inclusion of cost (initial and reintervention) and patient-centric outcomes in future studies evaluating lower extremity revascularization technologies. All journals, particularly vascular journals, should enforce standard reporting guidelines of effectiveness and economic studies to enable appropriate comparative and cost-effectiveness analyses. PMID- 21971094 TI - Invited commentary. PMID- 21971095 TI - Debate: whether abdominal aortic aneurysm surgery should be centralized at higher volume centers. AB - Volume-outcome relationships in vascular surgery have become increasingly relevant in recent years. At the individual surgeon level, increased experience has been linked with improved patient outcomes after volume-outcome and learning curve analyses. At the hospital level, further analyses have generally shown a similar relationship linking the busier hospitals with improved outcomes. However, is this relationship sufficient and robust enough to support important health care delivery decisions regarding centralization of care? In England, such information has helped to shape the vascular surgery reorganization process in London. The following discussion presents the advantages and disadvantages of the practical use of such information. PMID- 21971096 TI - Editors' commentary. PMID- 21971099 TI - Regarding "molecular diagnosis of nonaneurysmal infectious aortitis". PMID- 21971101 TI - Endoleaks and the unending saga of a clever new terminology that has proved counterproductive. PMID- 21971103 TI - Association between XRCC1 ARG399GLN and P53 ARG72PRO polymorphisms and the risk of gastric and colorectal cancer in Turkish population. AB - Gastric cancer is one of the most common cancers of the gastrointestinal system, and its overall five-year survival rate is still 15 % to 20 %, as it can mostly be diagnosed at an advanced stage. On the other hand, although colorectal cancer has a rather good prognosis, mortality is one half that of the incidence.As carcinogenesis is believed to involve reactive radicals that cause DNA adduct formation, impaired repair activity, and weakened tumour suppression, it would help to understand the role of the polymorphisms of nucleotide excision repair enzyme XRCC1 and of tumour suppressor gene p53 in gastric and colorectal cancers. Our study included 94 gastric cancer patients, 96 colorectal cancer patients, and 108 cancer-free individuals as control with the aim to see if there was an association between XRCC1 Arg399Gln and p53 Arg72Pro polymorphisms and cancer susceptibility. DNA was extracted from peripheral blood cells and genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism. Polymorphism p53 Arg72Pro was not associated with either gastric or colorectal carcinoma, while XRCC1 Arg399Gln was not associated with the increased risk of colorectal cancer. However, XRCC1 homozygous Gln allele at codon 399 was associated with 2.54 times higher risk of gastric cancer. PMID- 21971104 TI - Elimination of chloramphenicol in rainbow trout receiving medicated feed. AB - Chloramphenicol muscle residue levels in rainbow trout were determined after oral administration of 84 MUg kg-1d-1 of chloramphenicol for four days. Samples were taken one day before treatment and for 43 days after the treatment was over. Chloramphenicol was analysed using an in-house enzyme linked immunoassay (ELISA) validated against the criteria of the Commission Decision 2002/657/EC. Validation parameters confirmed that the method was appropriate for the detection of chloramphenicol at levels below the minimum required performance limit (MRPL) of 0.3 MUg kg-1. The highest chloramphenicol levels were observed on the first day after the treatment had ended (144.3 MUg kg-1). Elimination was significant over the first seven days; significant differences were detected between days 1 and 3 (p<0.001), 3 and 5 (p<0.001), and 5 and 7 (p<0.05). Chloramphenicol levels dropped below MRPL to 0.17 MUg kg-1 on day 9 after the end of treatment. From day 11 to 43, chloramphenicol residues were detectable in a range from 0.091 MUg kg-1 (highest) to 0.011 MUg kg-1 (lowest). Our results indicate that trout muscle tissue could be compliant with health requirements for consumption 10 days after withdrawal from chloramphenicol treatment. PMID- 21971105 TI - Cytotoxic and genotoxic effects of the quercetin/lanthanum complex on human cervical carcinoma cells in vitro. AB - Quercetin is the main flavonoid in diet with a potential in the treatment of cancer, cardiovascular, and neurodegenerative diseases. Due to its specific planar chemical structure, quercetin readily forms chelates with metal ions. Complexes of bioactive compounds and metal ions such as lanthanum often show strong cytotoxic and antitumour properties. The aim of this study was to compare the genotoxic effects of the quercetin/lanthanum complex on human cervical carcinoma cells with compare it to the effects of free ligands, quercetin, and lanthanum alone. The quercetin/lanthanum complex showed considerable cytotoxicity in the concentration range of (100 to 1000) mmol mL-1 and exposure time of three hours. The complex also induced a dose-dependent pro-oxidative effects and the formation of single-strand and double-strand DNA breaks. Although we obtained promising results on the cell level, future experiments should answer whether the quercetin/lanthanum complex is cancer-specific and stable enough in physiological conditions to make a potential new antitumour drug. PMID- 21971106 TI - Estimation of copper intake in moderate wine consumers in croatia. AB - To estimate Cu exposure level from wine consumption and to assess possible health risk for moderate wine consumers, wine samples were collected from different wine growing areas of Croatia. Median concentrations were 180 MUg L-1, range (76 to 292) MUg L-1, in commercial wines and 258 MUg L-1, range (115 to 7600) MUg L-1, in homemade wines (P>0.05). Maximum permitted level of 1000 MUg L-1 was exceeded in three homemade wines. However, daily intake of Cu from wine (in the range from 0.02 mg d-1 to 1.52 mg d-1) estimated from Cu concentration in all wine samples is lower than the tolerable upper intake level of 5 mg d-1 proposed by the EU Scientific Committee on Food and does not present a risk to moderate wine consumers. PMID- 21971107 TI - Side effects of adjuvant radiotherapy in men with testicular seminoma stage I. AB - In this study we followed up the side effects of adjuvant radiotherapy in patients with testicular seminoma stage I over a period from 13 to 84 months (median 28 months). The most frequent side effects during radiotherapy were gastrointestinal (nausea/vomiting), psychological, cognitive, and minor sexual problems.The reported side effects were treated by antiemetics and anxiolytics. After radiotherapy, the side effects persisted in 6 % of patients, but only a few of them required additional treatment. Healthy children were born to 76 % of patients in the 18 to 39 years age group. This study shows that adjuvant radiotherapy of the para-aortic lymph nodes with the total dosage of 24 Gy in 16 daily fractions administered to testicular seminoma patients causes acceptable side effects, does not adversely affect quality of life and fertility, if the approach to treatment is individual and family consulting is provided. This makes adjuvant radiotherapy of the para-aortic lymph nodes an acceptable treatment for testicular seminoma stage I patients. PMID- 21971108 TI - Volumetric assessment of airborne indoor and outdoor fungi at poultry and cattle houses in the Mazandaran Province, Iran. AB - The aim of this study was to assess the volume of airborne fungi in the indoor and outdoor environment of poultry and cattle houses in the Mazandaran Province in Iran. Indoor and outdoor air of twenty cattle houses and twenty-five poultry houses were sampled using a single-stage impactor, which draws air at 20 L min-1 and impacts sampled material onto Petri plates containing malt extract agar. The plates were incubated at 30 degrees C for seven days, after which the resulting colonies were counted. The fungi were identified and counted microscopically and macroscopically. A total of 4,662 fungal colonies were isolated from 90 plates collected from indoor and outdoor air of cattle and poultry houses. Cladosporium (55.3 %), yeast (10.0 %), and Aspergillus (9.4 %) were the most common findings. The concentration of airborne fungi in cattle and poultry houses ranged from 10 CFU m-3 to 1700 CFU m-3 in indoor and 10 CFU m-3 to 2170 CFU m-3 in outdoor environments. Cladosporium had the highest mean indoor (424.5 CFU m-3) and outdoor (449.7 CFU m-3) air concentration in the cattle houses. In the poultry houses, the highest mean concentrations were measured for Cladosporium (551.0 CFU m-3) outdoors and yeast (440.7 CFU m-3) indoors. These levels might present an occupational risk, but threshold levels for these environments have yet to be established worldwide. PMID- 21971109 TI - High-risk biodegradable waste processing by alkaline hydrolysis. AB - Biodegradable waste is by definition degraded by other living organisms. Every day, meat industry produces large amounts of a specific type of biodegradable waste called slaughterhouse waste. Traditionally in Europe, this waste is recycled in rendering plants which produce meat and bone meal and fat. However, feeding animals with meat and bone meal has been banned since the outbreaks of bovine spongiform encephalopathy (BSE). In consequence, new slaughterhouse waste processing technologies have been developed, and animal wastes have now been used for energy production. Certain parts of this waste, such as brains and spinal cord, are deemed high-risk substances, because they may be infected with prions. Their treatment is therefore possible only in strictly controlled conditions. One of the methods which seems to bear acceptable health risk is alkaline hydrolysis. This paper presents the results of an alkaline hydrolysis efficiency study. It also proposes reuse of the obtained material as organic fertiliser, as is suggested by the analytical comparison between meat and bone meal and hydrolysate. PMID- 21971110 TI - Survey of equipment quality control in radiotherapy centres in croatia: first results. AB - Implementation of advanced radiation therapy techniques in clinical practice can greatly improve tumour control and normal tissue sparing. An important part of this implementation is quality control (QC) of every part of the radiotherapy process, as it helps to detect errors and provides instant remedy. This increases the probability of successful radiation treatment and ensures patient radiation safety. Every radiotherapy quality assurance (QA) programme is based on quality control of radiotherapy equipment. The aim of our survey was to review QC practices in a number of radiotherapy centres in Croatia. As a first step, we defined a set of tests to check different parameters of linear accelerators and simulators in these centres. The tests were defined and performed according to protocols developed at two university hospitals. Test results varied largely between the centres. This calls for harmonisation of QC protocols. PMID- 21971111 TI - [Influence of daily set-up errors on dose distribution during pelvis radiotherapy]. AB - An external beam radiotherapy (EBRT) using megavoltage beam of linear accelerator is usually the treatment of choice in cancer patients. The goal of EBRT is to deliver the prescribed dose to the target volume, with as low as possible dose to the surrounding healthy tissue. A large number of procedures and different professions involved in radiotherapy, uncertainty of equipment and daily patient set-up errors can cause a difference between the planned and delivered dose.We investigated a part of this difference caused by measuring daily patient set-up errors for 35 patients. These set-up errors were simulated on five patients, using 3D treatment planning software XiO. The simulation investigated differences in dose distributions between the planned and shifted geometry. Additionally, we investigated the influence of the error on treatment plan selection by analysing changes in dose volume histograms, planning target volume conformity index (CIPTV), and homogeneity index (HI).Simulations showed that patient daily set-up errors can cause significant differences between the planned and actual dose distributions. Moreover, for some patients, those errors could affect the choice of treatment plan since CIPTV fell under 97%. Surprisingly, HI was not as sensitive to set-up errors as CIPTV. Our results have confirmed the need to minimise daily set-up errors through quality assurance programmes. PMID- 21971112 TI - [Risk assessment of human exposure to pesticides in food]. AB - This review presents methods for the assessment of acute and chronic risk from pesticide residues in food. Multiple pesticide residues can often be found in food. Currently, there is no internationally accepted procedure for the assessment of cumulative exposure to multiple pesticide residues in food. Therefore, risk assessment is based on toxicological evaluation of single compounds in a food matrix. The international estimation of short-term intake model (IESTI) has been used to calculate acute intake. IESTI is based on "the worst-case scenario" and addresses the possibility that consumers sometimes eat large amounts of a food item, and such a large amount might contain residues at highest levels. However, it should take into account uneven distribution of pesticide residues in food. Chronic exposure is based on a deterministic approach, analogous to the calculation of the theoretical maximum daily intake. PMID- 21971113 TI - [Notable radiophysicists and radiochemists in Croatia by 1945]. AB - Physicists and chemists were among the first potential victims of occupational exposure to ionising radiation and they were also the first to warn about the harmful effects of radiation on living organisms. This review presents the work of the first notable scientists in the field of radiation science in Croatia from the discovery of radiation (Henry Becquerel in 1896) to 1945. The beginning of radiation science and radiation protection in Croatia can be traced to the end of the 19th century. Our research of the archived material and literature not only gave a deeper insight to the life and work of some of these notable scientists, but also gave a glimpse of previously unknown facts and details important for the history and development of radiation science, radiation protection, as well as medical physics. Our research has shown that Croatian scientists not only kept pace with contemporary scientific knowledge but also made notable contributions from the very beginning. PMID- 21971115 TI - Influence of a long-term high-fat diet on ghrelin secretion and ghrelin-induced food intake in rats. AB - The aims of this study were: (1) to define the extent to which a high-fat (HF) diet given on a long-term basis reduces resting plasma ghrelin (total [acyl+des acyl]) levels and the plasma ghrelin (total) response to fasting, (2) to determine whether a chronic HF diet modifies the orexigenic activity of acyl ghrelin, (3) whether insulin pretreatment inhibits the plasma ghrelin (total) response to fasting, and (4) the extent to which pioglitazone (PIO) treatment will increase stomach and plasma ghrelin (total) levels in rats fed a HF diet. PIO is a drug given to diabetics which improves insulin resistance. Our findings show that a chronic HF diet given for either 10 or 60 weeks exerts a persistent inhibitory effect on resting plasma ghrelin (total) levels. Additionally, the plasma ghrelin (total) elevation to overnight fasting is not altered in rats fed a HF diet on a long-term basis. A HF diet does not impair the ingestive response to acyl-ghrelin. Together, these results suggest that acyl-ghrelin serves as an important orexigenic factor. Results show that insulin pretreatment does not inhibit the plasma ghrelin (total) response to fasting suggesting that meal induced insulin secretion does not have a role in reducing ghrelin (total) secretion. In rats fed a HF diet, PIO administration increases stomach ghrelin (total) levels. Because PIO can reduce systemic glucose and lipid levels, our findings suggest that elevated glucose and lipid levels are part of the inhibitory mechanism behind reduced ghrelin (total) secretion in rats fed a HF diet. PMID- 21971116 TI - Decrease of serum chemerin concentration in patients with end stage renal disease after successful kidney transplantation. AB - Chemerin is an adipokine associated with metabolic syndrome, systemic inflammation and innate immune system. It has been suggested recently that the decrease in renal function may cause an increase in serum chemerin concentration. In this paper we investigated the effect of kidney transplantation on elevated serum chemerin concentration in dialyzed patients with end stage renal disease (ESRD). Twenty five ESRD patients were tested before and 3months after the kidney transplantation. The control group was comprised of twenty one healthy subjects. Serum chemerin concentrations were measured using commercial ELISA kit, and were related to clinical status, and biomarkers of renal function. We have shown that the kidney transplantation resulted in the decrease of the serum chemerin concentration. Concomitantly, serum creatinine, blood urea nitrogen, phosphate and C-reactive protein concentrations were significantly reduced, while estimated glomerular filtration rate (eGFR), calcium and hemoglobin substantially increased. Univariate regression analysis showed that serum chemerin concentration was positively correlated with serum creatinine and phosphate concentrations and negatively correlated with eGFR. The results presented here indicate that the serum chemerin concentration in patients with ESRD normalizes after the kidney transplantation, and provide additional evidence that serum chemerin concentration is related to renal function. PMID- 21971117 TI - Role of tachykinin and neurokinin receptors in the regulation of ovine omasal contractions. AB - The present study investigated a role of tachykinins (TK) and neurokinin (NK) receptors (NK-R) in the non-cholinergic regulation of omasal contractions in sheep. Semiquantitative reverse transcription (RT)-PCR revealed that both preprotachykinin (PPT)-A and PPT-B mRNA were distributed in the omasal muscle layers and that NK-R type-1 (NK-1R) and type-2 (NK-2R) mRNA were largely expressed in the same tissues. Cumulative application of substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) at 0.03-10MUM induced tonic contractions of omasal muscle strips, and the contractile amplitude increased in order of NKB= 18 years) with C2 fractures without spinal cord injury who were treated with either fusion or halo-vest immobilization. Complication rates, hospital length of stay, and costs were compared in a propensity score matched sample. Multivariate analysis was used to identify predictors of in-hospital complications. RESULTS: A total of 3758 patients (1627 fusion and 2131 halo) were identified. Fusion was associated with greater overall complication rates (20.2% vs. 10.1%, P < 0.0001), increased length of stay (8.9 d vs. 6.4 d, P < 0.0001), higher charges ($80,000 vs. $41,000, P < 0.0001), but a lower rate of nonroutine discharge (52.6% vs. 62.6%, P < 0.0001). There was no difference in mortality between the fusion group (2.75%) and the halo group (3.33%). Age, injury score, and comorbidity increased complication rates by a similar degree (odds ratio) in both cohorts. Patients aged 80 years and older were 3.5 times more likely to have a complication than those younger than 60 years. CONCLUSION: Fusion patients had greater overall complication rates, increased length of stay, and greater resource utilization but were discharged home in a greater proportion. Both fusion and halo were associated with significant (more than 3-fold) increase in complication rates in elderly patients aged 80 years or older. Given the similar mortality rate between the fusion group and the halo group and the higher cost and complication rate in the fusion group, our study supports the use of halo vest immobilization in patients where operative therapy is contraindicated. PMID- 21971134 TI - The study on comparison of 3 techniques for transarticular screw placement in the lower cervical spine. AB - STUDY DESIGN: Prospective comparative study. OBJECTIVE: To compare 3 techniques for transarticular screw placement in the lower cervical spine. SUMMARY OF BACKGROUND DATA: The transarticular screw is found to have satisfactory biomechanical stability. According to current studies, there are several techniques for the placement of transarticular screws in the lower cervical spine. Although several techniques are available for transarticular screw implantation in the lower cervical spine, only a few studies in the literature have been carried out to compare these techniques. METHODS: The techniques of transarticular screw placement used by Takayasu (group A), Dalcanto (group B), and Klekamp (group C) were applied in 24 cervical specimens. The facet fractures, the encroachment of the cervical anterior branches of nerve roots and vertebral arteries and the failure of the screws to go through the facets were observed and analyzed. RESULTS: One hundred ninety-two transarticular screws were implanted on both sides in 24 cervical cadavers, 64 for each group. There were 25 splits of inferior facets in group B, 2 splits in group C, and none in group A. Thirty-six screws encroached the vertebral arteries in group A, none in groups B and C. Forty anterior branches of lower cervical nerve roots were involved in group A, 5 in group B, and 3 in group C. Although all screws went through facets in the study except for 5 in group A, there were no significant differences between each group (chi(AB)2 = 3.33, P > 0.05; chi(AC)2 = 3.33, P > 0.05). CONCLUSION: There is a high risk of injury to the anterior branch of the cervical nerve roots and vertebral artery if the screws were too long, and the Takayasu technique was used. However, the rate of facet splitting is high if the Dalcanto technique was applied. Klekamp's technique is recommended. PMID- 21971136 TI - Cellular adaptive response to glutathione depletion modulates endothelial dysfunction triggered by TNF-alpha. AB - Several interrelated cellular signaling molecules are involved in modulating adaptive compensatory changes elicited by low exposures to toxins and other stressors. The most prominent example of signaling pathway typically involved in this adaptive stress response, is represented by the activation of a redox sensitive gene regulatory network mediated by the NF-E2-related factor-2 (Nrf2) which is intimately involved in mediating the Antioxidant Responsive Element (ARE)-driven response to oxidative stress and xenobiotics. We investigated if Nrf2 pathway activation following intracellular glutathione depletion through buthionine sulfoximine (BSO) exposure, might be able to alter the response to TNF alpha, a proinflammatory cytokine, in cultured human umbilical vein endothelial cells. Herein, we revealed that such a change in the cellular redox status is able to reduce TNF-alpha induced endothelial activation (as shown by a decreased gene expression of adhesion molecules) by activating an adaptive response mediated by an increased Nrf2 nuclear translocation and overexpression of the ARE genes HO-1 and NQO-1. Furthermore, we have demonstrated the involvement of ERK1/2 kinases in Nrf2 nuclear translocation activated by BSO-induced glutathione depletion. The coordinate induction of endogenous cytoprotective proteins through adaptive activation of Nrf2 pathway is a field of great interest for potential application in prevention and therapy of inflammatory diseases such as atherosclerosis. PMID- 21971137 TI - Feasibility study of a unilateral RF array coil for MR-scintimammography. AB - Despite its high sensitivity, the variable specificity of magnetic resonance imaging (MRI) in breast cancer diagnosis can lead to unnecessary biopsies and over-treatment. Scintimammography (SMM) could potentially supplement MRI to improve the diagnostic specificity. The synergistic combination of MRI and SMM (MRSMM) could result in both high sensitivity from MRI and high specificity from SMM. Development of such a dual-modality system requires the integration of a radio frequency (RF) coil and radiation detector in a strong magnetic field without significant mutual interference. In this study, we developed and tested a unilateral breast array coil specialized for MRSMM imaging. The electromagnetic field, specific absorption ratio and RF coil parameters with cadmium-zinc telluride detectors encapsulated in specialized RF and gamma-ray shielding mounted within the RF coil were investigated through simulation and experimental measurements. Simultaneous MR and SMM images of a breast phantom were also acquired using the integrated MRSMM system. This work, we feel, represents an important step toward the fabrication of a working MRSMM system. PMID- 21971138 TI - [New strategy for treatment of patients with pancreatic cancer--clinical significance of peptide vaccine for pancreatic cancer]. PMID- 21971139 TI - [Neoadjuvant chemoradiation for the pancreatic cancer]. PMID- 21971140 TI - [Neoadjuvant chemotherapy for pancreatic carcinoma]. PMID- 21971141 TI - [Adjuvant gemcitabine plus S-1 chemotherapy for pancreatic cancer after surgical resection - outcomes and future perspectives]. PMID- 21971142 TI - [Evidences for adjuvant therapy of resected pancreatic cancer]. PMID- 21971143 TI - [A case of meningeal carcinomatosis due to gastric cancer treated with intrathecal chemotherapy]. AB - A 71-year-old man was admitted to our hospital in September 2009 because of severe headache due to meningeal carcinomatosis. In July 2007, subtotal gastrectomy was carried out for gastric cancer. Because intraabdominal cytodiagnosis was positive, he received systemic chemotherapy for 2 years. Recurrent signs were not found on chest or abdominal CT just before hospitalization. He was given NSAIDs and corticosteroid, but his symptom did not improve. Subsequent intrathecal chemotherapy with MTX and Ara-C improved clinical symptoms dramatically. He received care at home for 3 months before he passed away due to pleural and peritoneal recurrence. Recently, since the frequency of meningeal carcinomatosis is increasing, combination treatment of intrathecal chemotherapy and systemic chemotherapy should be considered not only for improvement of clinical manifestations, but also for prognostic improvement. PMID- 21971144 TI - [A case of malignant tumor of the ascending part of duodenum with osteoclast-like giant cells]. AB - Extraskeletal neoplasms with osteoclast-like giant cells are very rare. These tumors are most frequently reported in the breast and pancreas, and but rarely in other sites. We report a case of duodenal malignant tumor with osteoclast-like giant cells. The patient was a 76-year-old man who presented with vomiting. Computed tomography, magnetic resonance imaging, and gastrointestinal endoscopy revealed a giant tumor in the ascending part of duodenum. Biopsy specimens showed an undifferentiated malignant tumor with benign multinucleated giant cells. Immunohistochemical staining indicated that the tumor cells were reactive with vimentin, but not with epithelial markers or the other mesenchymal markers, and the multinucleated giant cells were reactive with CD68. Thus, we diagnosed a malignant tumor of the ascending part of duodenum with osteoclast-like giant cells. To the best of our knowledge, this is the first case of duodenal malignant tumor with osteoclast-like giant cells in Japan. PMID- 21971145 TI - [Recurrent autoimmune hemolytic anemia induced by XELOX chemotherapy for colon cancer]. AB - We describe a 54-year old woman with oxaliplatin-induced autoimmune hemolytic anemia and review the clinical features of similar published cases. The present patient had metastatic colon cancer and was admitted to our hospital with a floating sensation and general malaise on day 4 after undergoing the last of 4 cycles of a 7th round of chemotherapy with XELOX. Laboratory data revealed 4.6g/dl hemoglobin and 8.77 mg/dl creatinine. Direct and indirect Coombs tests of a blood sample for blood transfusion were both positive. We diagnosed immune hemolysis with acute renal failure based on the clinical course and blood samples showing haptoglobin <10mg/dl. We treated her with hemodialysis, plasmapheresis and immune suppression with prednisolone, which improved the anemia and renal failure. PMID- 21971146 TI - [A case of accessory papilla of duodenum causing intestinal bleeding]. AB - A 50-year-old man was admitted to our hospital with a chief complaint of melena. An emergency upper gastrointestinal endoscopic study revealed arterial bleeding from a duodenal submucosal tumor, 1.5cm in diameter and about 2cm in an oral direction from the papilla of Vater. Because it was not possible to stop the bleeding, an emergency resection of the tumor was performed. Macroscopically, the ulcerated tumor was approximately 1.5cm in diameter. Histopathologically, the tumor was determined to be located in the accessory papilla of the duodenum. We report here a rare case of bleeding from the accessory duodenal papilla and discuss the literature. PMID- 21971147 TI - [Intrahepatic portosystemic venous shunt via right renal vein successfully treated with balloon-occluded retrograde transvenous obliteration]. AB - A 66-year-old woman with a history of alcoholic liver cirrhosis and hepatocellular carcinoma was repeatedly hospitalized for the treatment of encephalopathy. Computed tomography demonstrated a portosystemic venous shunt which continued from portal branch P7 to the right renal vein. Since pharmacotherapy for encephalopathy was ineffective, balloon-occluded retrograde transvenous obliteration (B-RTO) was performed to block the portal-renal flow. Hyperammonemia and encephalopathy improved remarkably after the procedure. Intrahepatic portosystemic venous shunt draining into the right renal vein is a rare condition. To the best of our knowledge, management of this type of shunt by B-RTO has not been previously described. We report this case accompanied by a short review of the related literature. PMID- 21971148 TI - [Primary hepatic actinomycosis concomitant with elevation of protein induced by vitamin K absence or antagonist II - report of a case]. AB - We report a case of primary hepatic actinomycosis showing elevation of serum protein induced by vitamin K absence or antagonist II (PIVKA-II). A 68-year-old man visited an affiliated hospital with a complaint of high fever and body weight loss. Hematological examination revealed severe inflammatory reactions and liver dysfunction. Abdominal CT showed a heterogeneous low density area composed of cystic and solid part. We suspected the cystic part with band-like enhancement to be a hepatic abscess and performed percutaneous transhepatic abscess drainage. Although inflammatory reactions decreased after the drainage, the solid part did not shrink and blood chemistry revealed elevation of PIVKA-II. Since we could not rule out the possibility of hepatoma, right hepatectomy was performed. Histological examination revealed actinomycetes. Although primary hepatic actinomycosis is a rare disease, it must be kept in mind in the differential diagnosis of the liver tumor. PMID- 21971149 TI - [A case of early cystic duct carcinoma concomitant with xanthogranulomatous cholecystitis (XGC)]. AB - We reported a case of early cystic duct carcinoma concomitant with xanthogranulomatous cholecystitis (XGC). This case was a 72-year-old man in whom thickening of the gallbladder wall was pointed out an abdominal ultrasonography and elevation of the CA19-9 level was detected at a local clinic. Endoscopic ultrasonography and CT demonstrated a mass in the cystic duct. Mapping biopsy using peroral cholangioscopy (POCS) revealed a diagnosis of cystic carcinoma with superficial flat growth, therefore a pylorus-preserving pancreatoduodenectomy was performed. Histopathological diagnosis was well differentiated papillotubular adenocarcinoma with superficial flat spread and the thickening of the gallbladder wall was XGC. A case of early cystic duct carcinoma concomitant with XGC is extremely rare. PMID- 21971150 TI - [Mass-forming autoimmune pancreatitis caused after resection of an IgG4-related renal pelvic lesion]. AB - A 64-year-old man was found to have a 15-mm tumor in the pancreatic tail by CT angiography 1 year after resection of a left renal pelvic tumor. Clinically, the tumor was preoperatively suspected to be autoimmune pancreatitis. However, surgical resection was performed under a diagnosis of pancreatic ductal cancer, because atypical epithelial cells were detected by endoscopic ultrasonography guided fine needle aspiration (EUS-FNA). Pathological examination of the tumor revealed a mass-forming autoimmune pancreatitis. Mass-forming autoimmune pancreatitis is often difficult to preoperatively differentiate from pancreatic carcinoma. Response to steroid treatment and the detection of extrapancreatic lesions may contribute to an accurate diagnosis, thereby avoiding unnecessary surgery. PMID- 21971151 TI - 14-3-3 proteins--a family of universal scaffolds and regulators. PMID- 21971152 TI - Minireview: Stress-related psychiatric disorders with low cortisol levels: a metabolic hypothesis. AB - Several stress-associated neuropsychiatric disorders, notably posttraumatic stress disorder and chronic pain and fatigue syndromes, paradoxically exhibit somewhat low plasma levels of the stress hormone cortisol. The effects appear greatest in those initially traumatized in early life, implying a degree of developmental programming, perhaps of both lower cortisol and vulnerability to psychopathology. In these conditions, lowered cortisol is not due to any adrenal or pituitary insufficiency. Instead, two processes appear involved. First, there is increased target cell sensitivity to glucocorticoid action, notably negative feedback upon the hypothalamic-pituitary-adrenal (stress) axis. Altered density of the glucocorticoid receptor is inferred, squaring with much preclinical data showing early life challenges can permanently program glucocorticoid receptors in a tissue-specific manner. These effects involve epigenetic mechanisms. Second, early life trauma/starvation induces long-lasting lowering of glucocorticoid catabolism, specifically by 5alpha-reductase type 1 (predominantly a liver enzyme) and 11beta-hydroxysteroid dehydrogenase type 2 (in kidney), an effect also seen in model systems. These changes reflect a plausible early-life adaptation to increase the persistence of active cortisol in liver (to maximize fuel output) and kidney (to increase salt retention) without elevation of circulating levels, thus avoiding their deleterious effects on brain and muscle. Modestly lowered circulating cortisol and increased vulnerability to stress associated disorders may be the outcome. This notion implies a vulnerable early life phenotype may be discernable and indicates potential therapy by modest glucocorticoid replacement. Indeed, early clinical trials with cortisol have shown a modicum of promise. PMID- 21971154 TI - Serum IGF-I is not a reliable pharmacodynamic marker of exogenous growth hormone activity in mice. AB - Serum IGF-I is a well-established pharmacodynamic marker of GH administration in humans and has been used for this purpose in animal studies. However, its general suitability in wild-type laboratory mice has not been demonstrated. Here we show that treatment with recombinant human GH (rhGH) in four different strains of laboratory mice increases body weight, lean body mass, and liver weight but does not increase hepatic expression and release of IGF-I. In contrast and as expected, hypophysectomized rats show a rapid increase in serum IGF-I after rhGH administration. The lack of IGF-I up-regulation in mice occurs despite hepatic activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and is not explained by GH dose, route of administration, origin of GH (i.e. recombinant human, bovine, and murine GH), treatment duration, genetic background, sex, or formation of neutralizing antibodies. Effects on other components of the GH/IGF pathway were highly influenced by genetic background and sex but not consistently affected by rhGH treatment. We conclude that IGF-I is not a reliable indicator of the biological effects of exogenous GH treatment in genetically and pharmacologically unmodified mice. We speculate that IGF-I release is already maximal in these animals and cannot be further increased by exogenous GH treatment. This is also suggested by the observation of restored IGF-I up-regulation in isolated murine hepatocytes after rhGH treatment. Total body weight, lean body mass, and liver weight may be more reliable phenotypic indicators in these models. PMID- 21971153 TI - Cortistatin is not a somatostatin analogue but stimulates prolactin release and inhibits GH and ACTH in a gender-dependent fashion: potential role of ghrelin. AB - Cortistatin (CST) and somatostatin (SST) evolve from a common ancestral gene and share remarkable structural, pharmacological, and functional homologies. Although CST has been considered as a natural SST-analogue acting through their shared receptors (SST receptors 1-5), emerging evidence indicates that these peptides might in fact exert unique roles via selective receptors [e.g. CST, not SST, binds ghrelin receptor growth hormone secretagogue receptor type 1a (GHS-R1a)]. To determine whether the role of endogenous CST is different from SST, we characterized the endocrine-metabolic phenotype of male/female CST null mice (cort-/-) at hypothalamic-pituitary-systemic (pancreas-stomach-adrenal-liver) levels. Also, CST effects on hormone expression/secretion were evaluated in primary pituitary cell cultures from male/female mice and female primates (baboons). Specifically, CST exerted an unexpected stimulatory role on prolactin (PRL) secretion, because both male/female cort-/- mice had reduced PRL levels, and CST treatment (in vivo and in vitro) increased PRL secretion, which could be blocked by a GHS-R1a antagonist in vitro and likely relates to the decreased success of female cort-/- in first-litter pup care at weaning. In contrast, CST inhibited GH and adrenocorticotropin-hormone axes in a gender-dependent fashion. In addition, a rise in acylated ghrelin levels was observed in female cort-/- mice, which were associated with an increase in stomach ghrelin/ghrelin O-acyl transferase expression. Finally, CST deficit uncovered a gender-dependent role of this peptide in the regulation of glucose-insulin homeostasis, because male, but not female, cort-/- mice developed insulin resistance. The fact that these actions are not mimicked by SST and are strongly gender dependent offers new grounds to investigate the hitherto underestimated physiological relevance of CST in the regulation of physiological/metabolic processes. PMID- 21971155 TI - Estrous cycle- and sex-dependent changes in pre- and postsynaptic GABAB control of GnRH neuron excitability. AB - The GnRH neurons are the key neurons controlling fertility in mammals. Although gamma-aminobutyric acid (GABA) plays an important role in the regulation of GnRH neurons, the role of GABA(B) receptors is poorly understood. Using GnRH-green fluorescent protein transgenic mice and a parahorizontal brain slice preparation, we have undertaken a series of electrophysiological experiments to examine 1) postsynaptic GABA(B) receptors expressed by GnRH neurons, and 2) presynaptic GABA(B) receptors located on the terminals of an important neural input to GnRH neurons originating from the anteroventral periventricular nucleus (AVPV). The GABA(B) receptor agonist baclofen induced a direct postsynaptic hyperpolarization of GnRH neurons through induction of an outward current blocked by barium. Baclofen also acted presynaptically to suppress AVPV-activated GABA- and glutamate-evoked postsynaptic currents in GnRH neurons. The number of GnRH neurons exhibiting postsynaptic GABA(B) receptors was significantly (P < 0.05) different in males (22%) and females (70%), whereas presynaptic GABA(B) modulation of AVPV afferents was the same in the two sexes. Across the estrous cycle, a striking approximately 70% reduction (P < 0.05) in presynaptic GABA(B) modulation of AVPV afferents to GnRH neurons was found on proestrus compared with diestrus and estrus. In contrast, postsynaptic GABA(B) receptors did not change. Together, these findings show that GABA(B) receptors are active at both pre- and postsynaptic sites to modulate the excitability of GnRH neurons. The balance of this pre- and postsynaptic activity is different between the sexes and changes in a dynamic manner across the estrous cycle. PMID- 21971156 TI - Proprotein convertase 5/6 is critical for embryo implantation in women: regulating receptivity by cleaving EBP50, modulating ezrin binding, and membrane cytoskeletal interactions. AB - Establishment of endometrial receptivity is vital for successful embryo implantation; its failure causes infertility. Epithelial receptivity acquisition involves dramatic structural changes in the plasma membrane and cytoskeleton. Proprotein convertase 5/6 (PC6), a serine protease of the proprotein convertase (PC) family, is up-regulated in the human endometrium specifically at the time of epithelial receptivity and stromal cell decidualization. PC6 is the only PC member tightly regulated in this manner. The current study addressed the importance and mechanisms of PC6 action in regulating receptivity in women. PC6 was dysregulated in the endometrial epithelium during the window of implantation in infertile women of three demographically different cohorts. Its critical role in receptivity was evidenced by a significant reduction in mouse blastocyst attachment of endometrial epithelial cells after PC6 knockdown by small interfering RNA. Using a proteomic approach, we discovered that PC6 cleaved the key scaffolding protein, ezrin-radixin-moesin binding phosphoprotein 50 (EBP50), thereby profoundly affecting its interaction with binding protein ezrin (a key protein bridging actin filaments and plasma membrane), EBP50/ezrin cellular localization, and cytoskeleton-membrane connections. We further validated this novel PC6 regulation of receptivity in human endometrium in vivo in fertile vs. infertile patients. These results strongly indicate that PC6 plays a key role in regulating fundamental cellular remodeling processes, such as plasma membrane transformation and membrane-cytoskeletal interface reorganization. PC6 cleavage of a crucial scaffolding protein EBP50, thereby profoundly regulating membrane cytoskeletal reorganization, greatly extends the current knowledge of PC biology and provides substantial new mechanistic insight into the fields of reproduction, basic cellular biology, and PC biochemistry. PMID- 21971157 TI - Poly(A) tail length of neurohypophysial hormones is shortened under endoplasmic reticulum stress. AB - Familial neurohypophysial diabetes insipidus (FNDI) is caused by mutations in the gene locus of arginine vasopressin (AVP), an antidiuretic hormone. Although the carriers are normal at birth, polyuria and polydipsia appear several months or years later. Previously, we made mice possessing a mutation causing FNDI and reported that the mice manifested progressive polyuria as do the patients with FNDI. Here, we report that decreases in AVP mRNA expression in the supraoptic nucleus were accompanied by shortening of the AVP mRNA poly(A) tail length in the FNDI mice, a case in which aggregates accumulated in the endoplasmic reticulum (ER) of the hypothalamic AVP neurons. Expression levels of AVP heteronuclear RNA in the supraoptic nucleus, a sensitive indicator for gene transcription, were not significantly different between FNDI and wild-type mice. Incubation of hypothalamic explants of wild-type mice with ER stressors (thapsigargin and tunicamycin) caused shortening of the poly(A) tail length of AVP and oxytocin mRNA, accompanied by decreases in their expression. On the other hand, an ER stress-reducing molecule (tauroursodeoxycholate) increased the poly(A) tail length as well as the expression levels of AVP and oxytocin mRNA. These data reveal a novel mechanism by which ER stress decreases poly(A) tail length of neurohypophysial hormones, probably to reduce the load of unfolded proteins. PMID- 21971158 TI - Mechanisms underlying metformin-induced secretion of glucagon-like peptide-1 from the intestinal L cell. AB - Glucagon-like peptide-1(7-36NH2) (GLP-1) is secreted by the intestinal L cell in response to both nutrient and neural stimulation, resulting in enhanced glucose dependent insulin secretion. GLP-1 is therefore an attractive therapeutic for the treatment of type 2 diabetes. The antidiabetic drug, metformin, is known to increase circulating GLP-1 levels, although its mechanism of action is unknown. Direct effects of metformin (5-2000 MUm) or another AMP kinase activator, aminoimidazole carboxamide ribonucleotide (100-1000 MUm) on GLP-1 secretion were assessed in murine human NCI-H716, and rat FRIC L cells. Neither agent stimulated GLP-1 secretion in any model, despite increasing AMP kinase phosphorylation (P < 0.05-0.01). Treatment of rats with metformin (300 mg/kg, per os) or aminoimidazole carboxamide ribonucleotide (250 mg/kg, sc) increased plasma total GLP-1 over 2 h, reaching 37 +/- 9 and 29 +/- 9 pg/ml (P < 0.001), respectively, compared with basal (7 +/- 1 pg/ml). Plasma activity of the GLP-1-degrading enzyme, dipeptidylpeptidase-IV, was not affected by metformin treatment. Pretreatment with the nonspecific muscarinic antagonist, atropine (1 mg/kg, iv), decreased metformin-induced GLP-1 secretion by 55 +/- 11% (P < 0.05). Pretreatment with the muscarinic (M) 3 receptor antagonist, 1-1-dimethyl-4 diphenylacetoxypiperidinium iodide (500 MUg/kg, iv), also decreased the GLP-1 area under curve, by 48 +/- 8% (P < 0.05), whereas the antagonists pirenzepine (M1) and gallamine (M2) had no effect. Furthermore, chronic bilateral subdiaphragmatic vagotomy decreased basal secretion compared with sham-operated animals (7 +/- 1 vs. 13 +/- 1 pg/ml, P < 0.001) but did not alter the GLP-1 response to metformin. In contrast, pretreatment with the gastrin-releasing peptide antagonist, RC-3095 (100 MUg/kg, sc), reduced the GLP-1 response to metformin, by 55 +/- 6% (P < 0.01) at 30 min. These studies elucidate the mechanism underlying metformin-induced GLP-1 secretion and highlight the benefits of using metformin with dipeptidylpeptidase-IV inhibitors in patients with type 2 diabetes. PMID- 21971159 TI - Aldosterone-producing adenoma formation in the adrenal cortex involves expression of stem/progenitor cell markers. AB - Aldosterone producing adenoma (APA) is the most common form of surgically curable hypertension. To further understand mechanisms involved in APA formation, we investigated the expression of molecules linked to adrenal stem/precursor cells [beta-catenin, Sonic hedgehog (Shh), CD56], and nuclear receptors that play key roles in adrenocortical development and function steroidogenic factor 1, dosage sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1) in six control adrenal glands and 14 adrenals with APA and compared their expression with that of specific markers of zona glomerulosa (ZG) [CYP11B2, Disabled 2 (Dab2)]. Both Dab2 and CD56 were expressed in ZG. Although Dab2 associates uniquely with differentiated ZG cells and its expression is lost when cells transdifferentiate to zona fasciculata (ZF) cells, CD56 was also expressed in ZF and in aldosterone-producing cell clusters, confirming that these structures possess an intermediate phenotype between ZG and ZF cells. Shh was barely detectable in cells located to the outer part of the ZG in the control adrenal; in contrast, its expression was detected in the entire APA and was dramatically increased in the hyperplastic peritumoral ZG. Transcriptome profiling revealed differential expression of components of Shh signaling pathway in a subgroup of APA. Similarly, Wnt/beta-catenin signaling was activated in the majority of APA as well as in the entire peritumoral adrenal cortex; however, no mutation was identified in the CTNNB1 gene that could account for beta-catenin activation. Our data suggest that both APA and adjacent ZG present characteristics of stem/precursor cells; the reexpression of genes involved in fetal adrenal development could underlie excessive ZG cell proliferation and APA formation. PMID- 21971160 TI - Orexins/hypocretins act in the posterior paraventricular thalamic nucleus during repeated stress to regulate facilitation to novel stress. AB - Orexins/hypocretins heavily innervate the posterior division of the paraventricular nucleus of the thalamus (pPVT), which expresses both orexin receptor types. The pPVT is important for adaptations to repeated stress, particularly the ability to facilitate to novel stress after repeated stress exposure. Here, we examined how orexins acting in the pPVT regulate facilitation of hypothalamic-pituitary-adrenal (HPA) responses to novel restraint after 4 d of repeated swim stress. Blockade of orexin receptors in the pPVT with SB334867 before novel restraint did not change the facilitated HPA response. However, blockade of orexin receptors before each of four daily swim exposures prevented the facilitated ACTH and facilitated hypothalamic c-Fos response to restraint as well as the repeated swim stress-induced increase in CRH mRNA in the paraventricular hypothalamus. These results suggest that orexin actions in the pPVT during the 4 d of swim, but not during restraint, are necessary for the facilitated HPA response to heterotypic restraint. Exposure to the fourth swim produced a shift in orexin1 receptors from membrane to cytosolic fractions. OrexinA also changed the firing patterns of pPVT cells to be more responsive in repeatedly swim stressed rats compared with nonstressed rats. Together, the results suggest that orexin actions in the pPVT, mediated by orexin1 receptors, are important for the ability to adapt to repeated stress. PMID- 21971161 TI - Working memory processing of traumatic material in women with posttraumatic stress disorder. AB - BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with medial frontal and amygdala functional alterations during the processing of traumatic material and frontoparietal dysfunctions during working memory tasks. This functional magnetic resonance imaging (fMRI) study investigated the effects of trauma-related words processing on working memory in patients with PTSD. METHODS: We obtained fMRI scans during a 3-back task and an identity task on both neutral and trauma-related words in women with PTSD who had been sexually abused and in healthy, nonexposed pair-matched controls. RESULTS: Seventeen women with PTSD and 17 controls participated in the study. We found no behavioural working memory deficit for the PTSD group. In both tasks, deactivation of posterior parietal midline regions was more pronounced in patients than controls. Additionally, patients with PTSD recruited the left dorsolateral frontal sites to a greater extent during the processing of trauma-related material than neutral material. LIMITATIONS: This study included only women and did not include a trauma-exposed non-PTSD control group; the results may, therefore, have been influenced by sex or by effects specific to trauma exposure. CONCLUSION: Our results broadly confirm frontal and parietal functional variations in women with PTSD and suggest a compensatory nature of these variations with regard to the retreival of traumatic memories and global attentional deficits, respectively, during cognitively challenging tasks. PMID- 21971162 TI - Improving MMR vaccination rates: herd immunity is a realistic goal. AB - PROBLEM: As measles is a highly infectious disease, the United Kingdom recommendation is for at least 95% of children to receive a first vaccination with the measles, mumps, and rubella (MMR) vaccine before age 2 years and a booster before age 5 years to achieve herd immunity and prevent outbreaks. Reported vaccination rates for England have improved since a low level in 2003-4. Coverage for London is consistently lower than for England, however, and concerns have been expressed that there could be an epidemic of measles in the capital. DESIGN: Observational time series study. SETTING: London Borough of Tower Hamlets. Key measurements for improvement Uptake rates for childhood vaccinations. The key target was to reach 95% coverage for the first MMR vaccine before age 2 years. STRATEGIES FOR CHANGE: Financial support for the development of geographically based networks of general practices. Commissioning of care packages, incentivising delivery of high quality integrated care with network level vaccination targets of 95%. Innovative use of information technology to enable robust call and recall processes, active follow-up of defaulters, and increased knowledge about the demography of the children most difficult to reach. EFFECTS OF CHANGE: The development of networks of practices facilitated collaborative working among primary care clinicians and other stakeholders; peer review of achievements; and an element of healthy competition. Uptake improved for all childhood vaccinations, and to herd immunity levels for most. Uptake of the first MMR vaccine before age 2 years rose from 80% in September 2009 to 94% in March 2011. LESSONS LEARNT: Achieving herd immunity for childhood vaccinations is an achievable target in an ethnically mixed, socially deprived inner city borough. The ability to identify characteristics of the difficult to reach groups, including significant differences in uptake across different ethnicities, will allow targeted interventions that may further improve overall coverage. PMID- 21971163 TI - Some light on Islam and medical practices. PMID- 21971164 TI - Necrosis from needlestick injury with live Actinobacillus pleuropneumoniae porcine vaccine. PMID- 21971165 TI - Screening for falls may not be cost effective. PMID- 21971166 TI - Routine test batteries for cognitive impairment in older people may not be cost effective. PMID- 21971167 TI - Is it time for medicine to update its Facebook status? PMID- 21971168 TI - How to tackle the prescription opioid crisis. PMID- 21971169 TI - Ig Nobel awards celebrate studies of motion sickness, bladder control, and a mayor with an armoured tank. PMID- 21971170 TI - Chinese migrant workers are vulnerable to abortion risks, expert says. PMID- 21971171 TI - Rich countries can learn from poor ones about delivering good care at low cost, conference hears. PMID- 21971172 TI - Brain disorders cost Europe 800bn euro a year. PMID- 21971173 TI - Nobel winner dies three days before prize announcement. PMID- 21971174 TI - Abundance of prereplicative complexes (Pre-RCs) facilitates recombinational repair under replication stress in fission yeast. AB - Mcm2-7 complexes are loaded onto chromatin with the aid of Cdt1 and Cdc18/Cdc6 and form prereplicative complexes (pre-RCs) at multiple sites on each chromosome. Pre-RCs are essential for DNA replication and surviving replication stress. However, the mechanism by which pre-RCs contribute to surviving replication stress is largely unknown. Here, we isolated the fission yeast mcm6-S1 mutant that was hypersensitive to methyl methanesulfonate (MMS) and camptothecin (CPT), both of which cause forks to collapse. The mcm6-S1 mutation impaired the interaction with Cdt1 and decreased the binding of minichromosome maintenance (MCM) proteins to replication origins. Overexpression of Cdt1 restored MCM binding and suppressed the sensitivity to MMS and CPT, suggesting that the Cdt1 Mcm6 interaction is important for the assembly of pre-RCs and the repair of collapsed forks. MMS-induced Chk1 phosphorylation and Rad22/Rad52 focus formation occurred normally, whereas cells containing Rhp54/Rad54 foci, which are involved in DNA strand exchange and dissociation of the joint molecules, were increased. Remarkably, G(1) phase extension through deletion of an S phase cyclin, Cig2, as well as Cdt1 overexpression restored pre-RC assembly and suppressed Rhp54 accumulation. A cdc18 mutation also caused hypersensitivity to MMS and CPT and accumulation of Rhp54 foci. These data suggest that an abundance of pre-RCs facilitates a late step in the recombinational repair of collapsed forks in the following S phase. PMID- 21971176 TI - Platinum porphyrins as ionophores in polymeric membrane electrodes. AB - A comparative study of Pt(II)- and Pt(IV)-porphyrins as novel ionophores for anion-selective polymeric membrane electrodes is performed. Polymeric membranes of different compositions, prepared by varying plasticizers, cationic and anionic additives and Pt porphyrins, have been examined by potentiometric and optical techniques. Pt porphyrin-based devices were found to exhibit enhanced potentiometric selectivity toward iodide ion compared to electrodes based on a typical anion-exchanger (e.g. tridodecylmethylammonium chloride). It is shown that Pt(II)-porphyrins function as neutral anion carriers within the electrode membranes, while those based on Pt(IV)TPPCl(2) operate via a mixed mode carrier mechanism, evidencing also a partial reduction of the starting ionophore to Pt(II)TPP. Spectrophotometric measurements of thin polymeric films indicate that no spontaneous formation of hydroxide ion bridged porphyrin dimers occurs in the membrane plasticized both with high or low dielectric constant plasticizer, due to a low oxophilicity of central Pt. The computational study of various anion Pt(IV)TPPCl(2) complex formation by means of semi-empirical and density functional theory (DFT) methods revealed a good correlation between calculated and measured ionophore selectivity. PMID- 21971175 TI - The Escherichia coli clamp loader can actively pry open the beta-sliding clamp. AB - Clamp loaders load ring-shaped sliding clamps onto DNA. Once loaded onto DNA, sliding clamps bind to DNA polymerases to increase the processivity of DNA synthesis. To load clamps onto DNA, an open clamp loader-clamp complex must form. An unresolved question is whether clamp loaders capture clamps that have transiently opened or whether clamp loaders bind closed clamps and actively open clamps. A simple fluorescence-based clamp opening assay was developed to address this question and to determine how ATP binding contributes to clamp opening. A direct comparison of real time binding and opening reactions revealed that the Escherichia coli gamma complex binds beta first and then opens the clamp. Mutation of conserved "arginine fingers" in the gamma complex that interact with bound ATP decreased clamp opening activity showing that arginine fingers make an important contribution to the ATP-induced conformational changes that allow the clamp loader to pry open the clamp. PMID- 21971177 TI - Structures and vibrational spectroscopy of partially reduced gas-phase cerium oxide clusters. AB - This work demonstrates that the most stable structures of even small gas-phase aggregates of cerium oxide with 2-5 cerium atoms show structural motifs reminiscent of the bulk ceria. This is different from main group and transition metal oxide clusters, which often display structural features that are distinctly different from the bulk structure. The structures of Ce(2)O(2)(+), Ce(3)O(4)(+), and (CeO(2))(m)CeO(+) clusters (m = 0-4) are unambiguously determined by a combination of global structure optimizations at the density functional theory level and infrared vibrational predissociation spectroscopy of the cluster-rare gas atom complexes. The structures of Ce(2)O(2)(+) and Ce(2)O(3)(+) exhibit a Ce O-Ce-O four-membered ring with characteristic absorptions between 430 and 680 cm( 1). Larger clusters have common structural features containing fused Ce-O-Ce-O four-membered rings which lead to intense absorption bands at around 500 and 650 cm(-1). Clusters containing a terminal Ce=O bond show a characteristic absorption band between 800 and 840 cm(-1). For some cluster sizes multiple isomers are observed. Their individual infrared signatures are identified by tuning their relative population through the choice of He, Ne or Ar messenger atoms. The present results allow us to benchmark different density functionals which yield different degrees of localization of unpaired electrons in Ce 4f states. PMID- 21971179 TI - The HIF-1alpha-c-Myc pathway and tumorigenesis: evading the apoptotic gate keeper. PMID- 21971180 TI - In situ observation of morphological change in CdTe nano- and submicron wires. AB - We report growth and characterization of CdTe wires 30-400 nm in diameter by the vapor-liquid-solid technique. Individual nanowires were placed on a movable piezotube, which allowed three-dimensional motion toward a scanning tunneling microscope (STM). A bias was applied to the STM tip in contact with the nanowire, and the morphological changes due to Joule heating were observed in situ using a transmission electron microscope (TEM) in real time. For thick CdTe wires (d > ~150 nm), the process results in the growth of superfine nanowires (SFNWs) of 2-4 nm diameter on the surface of the wire. Smaller diameter nanowires, in contrast, disintegrate under the applied bias before the complete evolution of SFNWs on the surface. PMID- 21971178 TI - What makes transposable elements move in the Drosophila genome? AB - Transposable elements (TEs), by their capacity of moving and inducing mutations in the genome, are considered important drivers of species evolution. The successful invasions of TEs in genomes, despite their mutational properties, are an apparent paradox. TEs' transposition is usually strongly regulated to low value, but in some cases these elements can also show high transposition rates, which has been associated sometimes to changes in environmental conditions. It is evident that factors susceptible to induce transpositions in natural populations contribute to TE perpetuation. Different factors were proposed as causative agents of TE mobilization in a wide range of organisms: biotic and abiotic stresses, inter- and intraspecific crosses and populational factors. However, there is no clear evidence of the factors capable of inducing TE mobilization in Drosophila, and data on laboratory stocks show contradictory results. The aim of this review is to have an update critical revision about mechanisms promoting transposition of TEs in Drosophila, and to provide to the readers a global vision of the dynamics of these genomic elements in the Drosophila genome. PMID- 21971181 TI - Suppression of plant-generated reactive oxygen species is required for successful infection by the rice blast fungus. AB - Magnaporthe oryzae is a filamentous ascomycete that continuously threatens global rice production. The infection cycle of this pathogen commences with the attachment of conidia to rice plants, followed by the formation and maturation of a specialized infection structure-the appressorium. Melanized appressoria generate immense turgor pressure, which allows the fungus to break through the plant cuticle and cell wall by means of a penetration peg. These stages occur within the first twenty-four hours after which time the penetration peg gives rise to and subsequent primary and secondary infection hyphae. Upon infection, the plant recognizes the pathogen, triggering a series of defense responses and signaling events including the secretion of reactive oxygen species (ROS). In a recent paper, we showed that barley plants generate ROS and cell wall appositions (CWAs) around infection sites and that a fungal gene we termed MoHYR1 is necessary for ameliorating these defense reactions and ensuring successful infection and colonization. When this gene is deleted from the M. oryzae genome, the plant oxidative responses are stronger and disease is reduced. PMID- 21971182 TI - The two-component sensor kinase KinB acts as a non-canonical switch between acute and chronic infection. AB - P. aeruginosa is an opportunistic pathogen that occupies diverse environmental niches and is capable of causing a range of infections in humans. This versatility suggests that it has sophisticated mechanisms to sense and respond to the surrounding microenvironment. Two-component sensors are commonly used by bacteria to sense and respond to environmental stimuli and Pseudomonas aeruginosa has one of the largest sets of two-component sensors known in bacteria. We took advantage of a non-redundant transposon library and a recently characterized vertebrate model host, Danio rerio, that is amenable to higher throughput analysis than mammalian models, to systematically test the role of 60 two component sensors that are required for P. aeruginosa virulence in acute infection. We found that the sensor kinase KinB is required for acute infection in zebrafish embryos and regulates a number of virulence related phenotypes in a manner independent of its kinase activity and its known response regulator, AlgB. Thus, the regulation of virulence by KinB highlights the increasing recognition of non-canonical two-component signaling mechanisms. PMID- 21971184 TI - Salmonella and produce: survival in the plant environment and implications in food safety. AB - There has been a continuous rise in the number of produce-based foodborne outbreaks in the recent decades despite the perception that foodborne diseases were primarily linked to animal-based products. The Centers for Disease Control and Prevention (CDC) estimates that 95% of Salmonella-based infections originate from foodborne sources, with multiple produce-based salmonellosis outbreaks occurring since 1990. The contamination of produce in both the pre-harvest and post-harvest produce environments is challenging to eliminate since produce is consumed as a raw, fresh commodity. Salmonella spp. contamination is possible through contact with the produce in the field as well as in the processing facility. The field contamination of produce infers the ability of Salmonella spp. to survive on the plant surface. The fitness of Salmonella spp. in the plant habitat is limited as opposed to naturally plant-associated bacteria, but survival is possible. The use of intensive farming practices, globalization of food products, high demand for convenience food products, and increased foodborne disease surveillance also have unknown ramifications in the ascending trends of produce-based outbreaks. A better understanding of the ecology of Salmonella spp. in the plant environment as well as the processing, food handling, and surveillance factors affecting the incidence of foodborne outbreaks will provide a comprehensive view of the etiology and epidemiology of produce-associated foodborne outbreaks. An understanding of the outbreaks and the factors facilitating produce contamination will allow for the development of intervention procedures and strategies to reduce the risk of produce contamination by Salmonella spp. PMID- 21971185 TI - Muco-cutaneous leishmaniasis in the New World: the ultimate subversion. AB - Infection by the human protozoan parasite Leishmania can lead, depending primarily on the parasite species, to either cutaneous or mucocutaneous lesions, or fatal generalized visceral infection. In the New World, Leishmania (Viannia) species can cause mucocutaneous leishmaniasis (MCL). Clinical MCL involves a strong hyper-inflammatory response and parasitic dissemination (metastasis) from a primary lesion to distant sites, leading to destructive metastatic secondary lesions especially in the nasopharyngal areas. Recently, we reported that metastasizing, but not non-metastatic strains of Leishmania (Viannia) guyanensis, have high burden of a non-segmented dsRNA virus, Leishmania RNA Virus (LRV). Viral dsRNA is sensed by the host Toll-like Receptor 3 (TLR3) thereby inducing a pro-inflammatory response and exacerbating the disease. The presence of LRV in Leishmania opens new perspectives not only in basic understanding of the intimate relation between the parasite and LRV, but also in understanding the importance of the inflammatory response in MCL patients. PMID- 21971183 TI - All you need is light: antimicrobial photoinactivation as an evolving and emerging discovery strategy against infectious disease. AB - The story of prevention and control of infectious diseases remains open and a series of highly virulent pathogens are emerging both in and beyond the hospital setting. Antibiotics were an absolute success story for a previous era. The academic and industrial biomedical communities have now come together to formulate consensus beliefs regarding the pursuit of novel and effective alternative anti-infective countermeasures. Photodynamic therapy was established and remains a successful modality for malignancies but photodynamic inactivation has been transformed recently to an antimicrobial discovery and development platform. The concept of photodynamic inactivation is quite straightforward and requires microbial exposure to visible light energy, typically wavelengths in the visible region, that causes the excitation of photosensitizer molecules (either exogenous or endogenous), which results in the production of singlet oxygen and other reactive oxygen species that react with intracellular components, and consequently produce cell inactivation. It is an area of increasing interest, as research is advancing i) to identify the photochemical and photophysical mechanisms involved in inactivation; ii) to develop potent and clinically compatible photosensitizer; iii) to understand how photoinactivation is affected by key microbial phenotypic elements (multidrug resistance and efflux, virulence and pathogenesis determinants, biofilms); iv) to explore novel delivery platforms inspired by current trends in pharmacology and nanotechnology; and v) to identify photoinactivation applications beyond the clinical setting such as environmental disinfectants. PMID- 21971186 TI - The influenza A virus protein PB1-F2: killing two birds with one stone? AB - PB1-F2 is a 90 amino acid protein that is expressed from the +1 open reading frame in the PB1 gene of some influenza A viruses. The PB1-F2 protein has been shown to contribute to viral pathogenicity, but the molecular mechanisms for mediating virulence have been unclear. Previous reports demonstrate that PB1-F2 promotes cell death, causes immunopathology and increases pro-inflammatory responses. Our group has identified a single point mutation from asparagine (N) to serine (S) at position 66 in the PB1-F2 protein that dramatically increases the virulence of highly pathogenic avian H5N1 influenza viruses and of the 1918 pandemic strain. In search for the mechanism by which PB1-F2 N66S increases pathogenicity, we have identified and characterized a novel function of PB1-F2, i.e. interferon antagonism, both in vitro and in the mouse model. Here, we discuss a hypothesis for a possible molecular link between the pro-apoptotic and anti-interferon functions of PB1-F2. PMID- 21971187 TI - Staphylococcus aureus survival in human blood. AB - Methicillin-resistant Staphylococcus aureus (MRSA) is abundant in hospitals and in the United States is a leading cause of mortality due to infectious agents. Community-associated MRSA (CA-MRSA) strains such as USA300, which typically cause disease outside of healthcare settings, are also prevalent in the United States. Although most CA-MRSA infections affect skin and soft tissue, the pathogen can enter the bloodstream and ultimately cause severe disease. In a recent paper, we used USA300-specific microarrays to generate a comprehensive view of the molecules that facilitate S. aureus immune evasion and survival in human blood. Notably, genes encoding proteins involved in iron-uptake and utilization and gamma-hemolysin (hlgABC) are highly up-regulated by USA300 during culture in human blood. Here we discuss the potential implication of these findings and the possible role of gamma-hemolysin in the success of S. aureus as a human pathogen. PMID- 21971188 TI - Oral colonization of Gram-negative anaerobes as a risk factor for preterm delivery. AB - BACKGROUND: Preterm birth significantly impacts on neonatal morbidity and mortality and is apparently increasing world-wide. Several studies have attempted to define a causative role for periodontal disease in adverse pregnancy outcomes but few have focused on the microbiology of periodontal disease in relation to these outcomes. RESULTS: The evidence for a positive correlation is strong, supported by microbiological and immunological findings. Conflicting results are often associated with uncontrolled confounding factors. MATERIALS AND METHODS: A literature search was conducted in order to establish whether or not a role exists for oral Gram-negative bacteria in adverse pregnancy outcomes. Association and intervention studies are summarized along with pathogenic potential of the Gram-negative bacteria most frequently implicated in periodontal disease. PMID- 21971189 TI - Transplantation: Desensitization and transplantation for sensitized patients? PMID- 21971190 TI - Risk factors: Levels of FGF23 predict outcomes in advanced CKD. PMID- 21971191 TI - Polycystic kidney disease: Glomerular hyperfiltration may be a risk factor for progression of ADPKD. PMID- 21971192 TI - Acute kidney injury: Acetylcysteine does not prevent contrast-induced acute kidney injury. PMID- 21971193 TI - Minimal hilar dissection prevents biliary anastomotic stricture after living donor liver transplantation. AB - BACKGROUND: We introduced a new technique called minimal hilar dissection (Min HD) technique in living donor liver transplantation (LDLT) to keep vascular networks around the recipient's bile duct. The aim of this study is to investigate whether the Min-HD technique could prevent biliary anastomotic stricture (BAS) after LDLT with duct-to-duct biliary reconstruction. METHODS: An analysis of 214 adult-to-adult LDLT grafts (left lobe, n=135; right lobe, n=76; posterior segment, n=3) with duct-to-duct biliary reconstruction was performed. RESULTS: There were 46 cases with BAS. The incidence of BAS was 32.1% in the conventional technique group (n=84) and 14.6% in the Min-HD technique group (n=130, P=0.003). Multivariate regression analysis regarding BAS was carried out and detected hepatic artery flow less than 50 mL/min (P=0.002), not using the Min HD technique (P=0.011), biliary anastomotic leakage (BAL, P=0.027) and ductoplasty (P=0.039) for the significant risk factors for BAS. The incidence BAL was 11.9% in the conventional technique group and 0.7% in the Min-HD technique group (P=0.002). No other factors showed an impact on the occurrence of BAL. The treatments for BAS were performed by endoscopic or percutaneous procedures. The cumulative completion rate of the treatment after developing BAS was 45.1% and 78.6% at 1- and 3-year, respectively. The median period for treating BAS was 10.8 months. CONCLUSION: The Min-HD technique is a rational surgical method, and it has the potential for preventing BAS and BAL after duct-to duct biliary reconstruction in LDLT. PMID- 21971194 TI - The History of Greek Psychiatry through the texts of those who have shaped it. PMID- 21971195 TI - [Neurocognitive function in clinically stable patients with schizophrenia or bipolar disorder and normal controls]. AB - There is a substantial body of evidence suggesting that cognitive deficits in schizophrenia (SZeta) and bipolar disorder (BD) persist after the subsidence of active symptoms. However, it is unclear whether the cognitive deficits observed in patients with BD are quantitatively or qualitatively similar to those in SZeta patients. The aim of the study was to assess and compare the cognitive functioning of patients with clinically stable SZ and BD. To the best of our knowledge, this is the first study including a comparison of the Theory of Mind between patients with SZ and BD. General intelligence, attention, speed of processing, working memory, verbal memory and learning, visuospatial ability, executive functions and ToM were assessed in 21 patients with SZ in remission, 23 euthymic BD type I patients, and 27 healthy controls (HC), using WAIS-Vocabulary, Block design, and Digit span, Babcock Story Recall Test, Rey Auditory Verbal Learning Test, Stroop Word-Colour Test, Wisconsin Card Sorting Test, Trail Making Test, and Faux Pas Recognition Test. The three groups were matched for gender, age and education. The SZ and BD groups were also matched in terms of illness duration and the age of the onset of the illness. To be enrolled in the study patients should have been clinically stable for 3 months, operationalized as no change in total Brief Psychiatric Rating Scale, Hamilton Depression Rating Scale (<8), and Young Mania Rating Scale (<6). One-way ANOVA with post hoc Bonferroni corrections was used for the between groups comparisons. Both BD and SC patients were significantly impaired in general intellectual ability, verbal memory and learning, and executive functions compared to HC. Patients with SZ performed significantly worse than patients with BD on verbal memory tasks, whereas BD group did not have significant lower score than SZ in any task. SZ patients performed worse than HC group on attention, processing speed and immediate memory tests, while BD patients on visuospatial ability and working memory. Both SZ and BD groups did not differ from HC regarding Theory of Mind. Our results indicate that stable SZ and euthymic BD exhibit similar profiles of cognitive impairment, consistently with previous studies suggesting that the differences are related to the extent and degree of impairments, rather than being qualitative. Finally, our findings offer support to the hypothesis that the Theory of Mind does not represent a trait marker of schizophrenia or bipolar disorder. PMID- 21971196 TI - [The Life Style Index: correlations with psychological distress and hostility]. AB - The Life Style Index (LSI) was designed to assess defense mechanisms, assuming that their use is related to specific emotional states and diagnostic concepts. Aiming to further investigate the psychometric properties of the Greek version of the LSI, the aim of the present study was to investigate the relationship of specific defense mechanisms with dimensions of psychological distress and hostility features in three different populations. The sample comprised 1261 adults (410 healthy participants, 723 medical patients and 128 psychiatric patients). Along with defense mechanisms (LSI), Psychological Distress (General Health Questionnaire, GHQ-28) and Hostility features (Hostility and Direction of Hostility Questionnaire, HDHQ) were also assessed. The results showed that increased psychological distress is related with increased use of all defenses except Denial, with which psychological distress is negatively associated. Regression is constantly related with psychological distress and differentiates psychiatric patients from the other groups of participants, while Compensation and Reaction Formation are related to depressive symptomatology. In medical patients, Repression was found to increase the physical dimension of psychological distress and the social dysfunction. On the contrary,Denial was negatively associated with these dimensions of psychological distress. In the psychiatric patient and healthy participant samples, Projection plays the most detrimental role. Regarding hostility and direction of hostility, those who were found to introvert their hostility presented with higher scores in Denial, indicating that they possibly 'deny' their hostility, and the degree of the Denial was found to be negatively associated with the degree of Introverted Hostility. Those who directed their hostility towards the others, presented with higher rates of Projection, while neither Denial nor Reaction Formation seemed sufficient enough to temper the degree of Extroverted Hostility. In conclusion,the present results strengthen further the validity of the Greek version of the LSI and provide additional evidence about the relation of defence mechanisms with dimensions of psychological distress and the direction of hostility in different populations, indicating that the empirical assessment of defense mechanisms can contribute significantly in the study of the factors that mediate or moderate the course or the outcome of medical or psychiatric disorders. PMID- 21971197 TI - [Internet use and pathological internet engagement in a sample of college students]. AB - Recent studies indicate multiple consequences of pathologically excessive internet use. This study investigated the correlate of internet usage, with pathological internet engagement. Participants were 514 college students from the University of Athens who completed a questionnaire covering various aspects of internet use, Young's Internet Addiction Test, scales investigating online gambling addiction and cybersexual addiction and scales investigating suicidal ideation and the use of psychoactive substances. We found that the daily Internet use (b=0,38, t=10,38, p<0,001), the use of interactive online games (b=0,21, t=5,15, p<0,001), making acquaintances on the internet (b=0,20, t=5,11, p<0,001) and the participation in online forums (b=0,15, t=3,64, p<0,001) account for 42% of the variance of pathological internet engagement. Subjects at risk for developing pathological internet engagement had significantly higher levels of online gambling addiction, cybersexual addiction, suicidal ideation and alcohol abuse, compared with other groups. Pathological internet engagement, particularly in young people, is a new psychopathological parameter that should be incorporated in the diagnostic and therapeutic horizon of mental health professionals. PMID- 21971198 TI - [Eating disorders and mass media]. AB - During the last 50 years, eating disorders have developed to a complicated and widespread medical and social issue. The latest research results indicate that eating disorders have a quite complicated and multifactorial etiology. According to the multifactorial etiological model, the impact of mass media can be regarded mainly as a precipitating factor. The literature review showed that mass media have a considerable impact on the development and perpetuation of eating disorders. Mass media contribute to the promotion of the thinness ideal as a way to achieve social approval, recognition and success. Mass media also promote dieting and food deprivation, as a successful way of life or as a socially agreeable practice. Furthermore, the literature review showed that mass media remain the main source of information about eating disorders. Considering the above result, mass media could play a major role in the promotion of prevention practices and early diagnosis and treatment of eating disorders. PMID- 21971199 TI - [Post-stroke depression: recognition and treatment interventions]. AB - Depression is the most common neuropsychiatric complication of a stroke (Post Stroke DepressionPSD) and has been shown to impede the recovery and rehabilitation of these patients. Prevalence rates of PSD vary between 6% and 79%. Direct comparison between studies is limited due to their different methodology. Etiology of PSD is determined by biological and psychosocial factors. Symptoms of PSD appear in three areas: affective, somatic and cognitive. Differential diagnosis includes post-stroke fatigue and pseudo depressive manifestations of ischemic infarctions (apathy, aprosody, athymhormia, pseudobulbar palsy). Mortality in post-stroke patients is higher than in non depressed stroke patients and suicide ideation is observed in 6.6-11.3% of stroke patients. Selective serotonin reuptake inhibitors (SSRI) are considered as the first choice treatment of PSD. Other therapeutic approaches include cognitive and functional rehabilitation. PSD is a potentially treatable condition, yet under-diagnosed, and has a negative effect on functional recovery and survival of stroke patients. PMID- 21971200 TI - [The spectrum of Tourette Syndrome and difficulties in differential diagnosis: a case report]. AB - Tourette syndrome (TS) is a neurodevelopmental disorder characterized by early onset motor and vocal tics. TS should be differentiated from various movement disorders. We report the case of a 21 year-old-man who was admitted to our clinic due to treatment resistant cervical dystonia attributed to neuroleptics. During the last five years he had been treated for depressed mood, somatic delusions and aggressive behaviour. He had been given SSRIs and atypical antipsychotics at low doses; six months prior to his admission he had been switched to risperidone. Clinical examination revealed torticollis, motor stereotypies, vocal tics (sniffing, repetition of words), mental koprolalia and obsessive-compulsive symptoms. He complained of repetitive intrusive thoughts of harming his sister and thoughts of a "delusional" nature regarding somatic complaints. The patient was diagnosed as TS and was successfully treated accordingly. The presented case illustrates that TS can mimic other movement disorders. Whether patients with TS are at higher risk of developing dystonia, or tics and dystonia share a common pathophysiological mechanism (dopamine inhibiting processes are probably involved in both conditions) is still debatable. PMID- 21971201 TI - Analytic expression of fluorescence ratio detection correlates with depth in multi-spectral sub-surface imaging. AB - Here we derived analytical solutions to diffuse light transport in biological tissue based on spectral deformation of diffused near-infrared measurements. These solutions provide a closed-form mathematical expression which predicts that the depth of a fluorescent molecule distribution is linearly related to the logarithm of the ratio of fluorescence at two different wavelengths. The slope and intercept values of the equation depend on the intrinsic values of absorption and reduced scattering of tissue. This linear behavior occurs if the following two conditions are satisfied: the depth is beyond a few millimeters and the tissue is relatively homogeneous. We present experimental measurements acquired with a broad-beam non-contact multi-spectral fluorescence imaging system using a hemoglobin-containing diffusive phantom. Preliminary results confirm that a significant correlation exists between the predicted depth of a distribution of protoporphyrin IX molecules and the measured ratio of fluorescence at two different wavelengths. These results suggest that depth assessment of fluorescence contrast can be achieved in fluorescence-guided surgery to allow improved intra-operative delineation of tumor margins. PMID- 21971202 TI - Features associated with cardiac abnormalities in systemic lupus erythematosus. AB - OBJECTIVES: To determine the prevalence of echocardiographic abnormalities and identify associated clinical and laboratory features in a large systemic lupus erythematosus (SLE) cohort. METHODS: Patients fulfilling ACR criteria for SLE underwent a transthoracic echocardiogram (TTE) between January 2005 and June 2006. Variables used as potential correlates included age, sex, ethnicity, lupus duration, lupus disease activity (SLEDAI), cumulative damage (SLICC/ACR damage index (DI)), arterial hypertension, diabetes, current smoking, medication use and laboratory data. Multivariate logistic regression was used to examine the association between TTE abnormalities and potential determinants. RESULTS: For the 217 subjects with a TTE performed during the study, the main abnormalities were of the mitral valve (37.3%) and included thickening (25.4%) and insufficiency (25.8%). Other findings included pulmonary artery pressure (PAP) >= 30( )mm( )Hg (10.1%), pericardial effusion (4.6%), hypokinesis (2.8%), and aortic insufficiency (3.7%). In multivariate analysis, mitral insufficiency was associated with the use of corticosteroids (OR 2.90; 95%CI 1.42-5.94) and hypokinesis with angiotensin-converting enzyme inhibitors (12.89; 1.06-157.18). Elevated PAP was associated with age (1.04; 1.01-1.07) and with DI (1.20; 1.01 1.42). CONCLUSION: Valvular abnormalities are frequent in patients with SLE, with mitral valve lesions occurring in over one third. TTE screening may be indicated in patients with SLE, especially for those with identified risk factors such as corticosteroid use. PMID- 21971203 TI - Resonant IR multi-photon dissociation spectroscopy of a trapped and sympathetically cooled biomolecular ion species. AB - In this work we demonstrate vibrational spectroscopy of polyatomic ions that are trapped and sympathetically cooled by laser-cooled atomic ions. We use the protonated dipeptide tryptophan-alanine (HTyrAla(+)) as a model system, cooled by barium ions to less than 800 mK secular temperature. The spectroscopy is performed on the fundamental vibrational transition of a local vibrational mode at 2.74 MUm using a continuous-wave optical parametric oscillator (OPO). Resonant IR multi-photon dissociation spectroscopy (R-IRMPD) (without the use of a UV laser) generates charged molecular fragments, which are sympathetically cooled and trapped, and subsequently released from the trap and counted. We measured the cross section for R-IRMPD under conditions of low intensity, and found it to be approximately two orders smaller than the vibrational excitation cross section. The observed rotational bandwidth of the vibrational transition is larger than the one expected from the combined effects of 300 K black-body temperature, conformer-dependent line shifts, and intermolecular vibrational relaxation broadening (J. Stearns et al., J. Chem. Phys., 2007, 127, 154322-154327). This indicates that as the internal energy of the molecule grows, an increase of the rotational temperature of the molecular ions well above room temperature (up to on the order of 1000 K), and/or an appreciable shift of the vibrational transition frequency (approx. 6-8 cm(-1)) occurs. PMID- 21971204 TI - In situ ATR-IR study of prochiral 2-methyl-2-pentenoic acid adsorption on Al2O3 and Pd/Al2O3. AB - Adsorption and desorption of trans-2-methyl-2-pentenoic acid (MPeA) in dichloromethane (CH(2)Cl(2)) were investigated by using in situ attenuated total reflection infrared (ATR-IR) spectroscopy. A liquid flow-through spectroscopic cell allowed for high quality spectra to be obtained from deposited thin films of Al(2)O(3) and 1 wt% Pd/gamma-Al(2)O(3) on a ZnSe internal reflection element. The MPeA molecules adsorb on both Al(2)O(3) and Pd surfaces molecularly and dissociatively under the concentration range examined (2-16 mM). In the case of molecular adsorption, both monomer (nu(C=O) ~ 1720 cm(-1)) and dimer (nu(C=O) ~ 1685 cm(-1)) species are observed to adsorb, with the relative amount of monomer to dimer dependent on the surface and the liquid phase acid concentration. In the case of dissociative adsorption, the acid adsorbs predominantly in a bridged bidentate configuration, as adjudged by the ca. 150-220 cm(-1) separation between asymmetric and symmetric vibrational bands. All of these species are found to be strongly adsorbed on both Al(2)O(3) and 1 wt% Pd/gamma-Al(2)O(3) surfaces, even under pure solvent flow after adsorption. PMID- 21971206 TI - Pain treatment after craniotomy: where is the (procedure-specific) evidence? A qualitative systematic review. AB - CONTEXT AND OBJECTIVE: Pain following craniotomy has been demonstrated to be frequent and moderate-to-severe in nature. In recent years, the focus on the challenges in treatment of postoperative pain following craniotomy has increased. Fear of using opioids because of their wide array of side-effects has led to the search for alternative analgesic options. The objective of this systematic review was to evaluate current evidence about analgesic therapy following craniotomy. DATA SOURCES: PubMed database, Embase, Cochrane library, Google scholar and the Cumulative Index to Nursing and Allied Health Literature. ELIGIBILITY CRITERIA: Randomised double-blinded placebo-controlled trials (RCTs) with pain or supplemental postoperative analgesic consumption as an endpoint were included in the analysis. RESULTS: A total of 34 RCTs were identified, and nine RCTs were included in the final analysis, with a total of 519 patients (251 control vs. 268 active treatment). Four treatment modalities - scalp infiltration (five RCTs), nerve scalp block (two RCTs), parecoxib (one RCT) and patient-controlled analgesia with morphine (one RCT) - were evaluated. Scalp infiltration with local anaesthetic may provide adequate analgesia in the first few postoperative hours, and nerve scalp block may provide longer lasting analgesia for about 6 h. Morphine was found to reduce total analgesic rescue doses with no significant effect on nausea and no other side-effects. No significant evidence was found to support the use of parecoxib in the treatment of postcraniotomy pain. CONCLUSION: No firm recommendations on analgesic therapy following craniotomy can be given because the number of well performed RCTs is limited and the study populations are very small. However, evidence on scalp infiltration suggests an analgesic effect in the first few postoperative hours. There is an urgent need for well performed RCTs on pain therapy following craniotomy. PMID- 21971207 TI - Chemical composition, antinociceptive and anti-inflammatory effects in rodents of the essential oil of Peperomia serpens (Sw.) Loud. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Peperomia serpens (Piperaceae), popularly known as "carrapatinho", is an epiphyte herbaceous liana grown wild on different host trees in the Amazon rainforest. Its leaves are largely used in Brazilian folk medicine to treat inflammation, pain and asthma. AIM OF THE STUDY: This study investigated the effects of essential oil of Peperomia serpens (EOPs) in standard rodent models of pain and inflammation. MATERIALS AND METHODS: The antinociceptive activity was evaluated using chemical (acetic acid and formalin) and thermal (hot plate) models of nociception in mice whereas the anti inflammatory activity was evaluated by carrageenan- and dextran-induced paw edema tests in rats croton oil-induced ear edema, as well as cell migration, rolling and adhesion induced by carrageenan in mice. Additionally, phytochemical analysis of the EOPs has been also performed. RESULTS: Chemical composition of the EOPs was analyzed by gas chromatography and mass spectrometry (GC/MS). Twenty-four compounds, representing 89.6% of total oil, were identified. (E)-Nerolidol (38.0%), ledol (27.1%), alpha-humulene (11.5%), (E)-caryophyllene (4.0%) and alpha-eudesmol (2.7%) were found to be the major constituents of the oil. Oral pretreatment with EOPs (62.5-500 mg/kg) significantly reduced the writhing number evoked by acetic acid injection, with an ED(50) value of 188.8 mg/kg that was used thereafter in all tests. EOPs had no significant effect on hot plate test but reduced the licking time in both phases of the formalin test, an effect that was not significantly altered by naloxone (0.4 mg/kg, s.c.). EOPs inhibited the edema formation induced by carrageenan and dextran in rats. In mice, EOPs inhibited the edema formation by croton oil as well as the leukocyte and neutrophil migration, the rolling and the adhesion of leukocytes. CONCLUSIONS: These data show for the first time that EOPs has a significant and peripheral antinociceptive effect that seems unrelated to interaction with the opioid system. EOPs also displays a significant anti-inflammatory effect in acute inflammation models. This effect seems to be related to components which inhibit the production of several inflammatory mediators. These results support the widespread use of Peperomia serpens in popular medicine to treat inflammation and pain. PMID- 21971208 TI - Chronic medical conditions and reproducibility of self-reported age at menopause among community-dwelling women. AB - OBJECTIVE: The aim of this study was to examine the association between chronic medical conditions and reproducibility of self-reported age at menopause among community-dwelling women. METHODS: Age at menopause was assessed in a population based longitudinal survey of 240 women twice, in 1993 and 2004. Women who recalled age at menopause in 2004 within 1 year or less of age at menopause recalled in 1993 (concordant) were compared with women who did not recall age at menopause in 2004 within 1 year of age at menopause recalled in 1993 (discordant). Type of menopause (surgical or natural) and chronic medical conditions were assessed by self-report. RESULTS: One hundred forty-three women (59.6%) reported surgical menopause, and 97 (40.4%) reported natural menopause. In all, 130 (54.2%) women recalled age at menopause in 2004 within 1 year or less of recalled age at menopause in 1994, whereas 110 (45.8%) women did not recall age at menopause in 2004 within 1 year or less of recalled age at menopause in 1994. Among the women with surgical menopause, the women with three or more medical conditions were less likely to have concordant recall of age at menopause than the women with less than three chronic medical conditions (adjusted odds ratio, 0.36; 95% CI, 0.15-0.91) in multivariate models controlling for potentially influential characteristics including cognition and years since menopause. CONCLUSIONS: Among women who underwent surgical menopause, the presence of three or more medical conditions is associated with decreased reproducibility of self-reported age at menopause. PMID- 21971209 TI - Adiponectin and leptin serum levels in osteoporotic postmenopausal women treated with raloxifene or alendronate. AB - OBJECTIVE: Clinical studies evaluating the role of leptin and adiponectin on bone metabolism had shown conflicting results, and data about the effect of anticatabolic drugs on these adipokines are scarce. Our aims were to determine adiponectin and leptin levels in osteoporotic postmenopausal women and their relationship with bone mass and bone turnover and to analyze changes on adiponectin and leptin levels after treatment with raloxifene or alendronate. METHODS: We selected 53 women (mean +/- SD age, 63 +/- 7 y) with postmenopausal osteoporosis divided into two treatment groups: raloxifene (60 mg/d; n = 20) or alendronate (70 mg/wk; n = 33) during a period of 1 year. Bone mineral density by dual-energy x-ray absorptiometry and serum levels of leptin, adiponectin, and bone turnovers markers were determined at baseline and at 1 year after treatment. RESULTS: Baseline levels of leptin were correlated to body mass index (r = 0.47; P < 0.01), waist circumference (r = 0.38, P = 0.01), and estradiol (r = 0.4, P = 0.003). Adiponectin was inversely related to bone-specific alkaline phosphatase (r = -0.41, P < 0.01) and serum crosslaps (r = -0.35; P < 0.01). There was no correlation between bone mineral density, leptin, and adiponectin. After 12 months, no changes were observed in leptin and adiponectin in the alendronate group; however, a significant increase in leptin levels (973.5 +/- 637.4 pM/mL vs 1,305.7 +/- 793.5 pM/mL; P = 0.031) was detected in the raloxifene group, whereas adiponectin levels showed no significant changes (P = 0.46). CONCLUSIONS: In postmenopausal women with osteoporosis, raloxifene induces a significant increase in leptin levels without significant changes in adiponectin serum levels. The antiresorptive effect of raloxifene and alendronate is not substantially influenced by changes in leptin or adiponectin levels. PMID- 21971210 TI - Menopause as risk factor for oxidative stress. AB - OBJECTIVE: The aim of this study was to determine the influence of menopause (hypoestrogenism) as a risk factor for oxidative stress. METHODS: We carried out a cross-sectional study with 187 perimenopausal women from Mexico City, including 94 premenopausal (mean +/- SD age, 44.9 +/- 4.0 y; estrogen, 95.8 +/- 65.7 pg/mL; follicle-stimulating hormone, 13.6 +/- 16.9 mIU/mL) and 93 postmenopausal (mean +/- SD age, 52.5 +/- 3.3 y; estrogen, 12.8 +/- 6.8 pg/mL; follicle-stimulating hormone, 51.4 +/- 26.9 mIU/mL) women. We measured lipoperoxides using a thiobarbituric acid-reacting substance assay, erythrocyte superoxide dismutase and glutathione peroxidase activities, and the total antioxidant status with the Randox kit. An alternative cutoff value for lipoperoxide level of 0.320 MUmol/L or higher was defined on the basis of the 90th percentile of young healthy participants. All women answered the Menopause Rating Scale, the Athens Insomnia Scale, and a structured questionnaire about pro-oxidant factors, that is, smoking, consumption of caffeinated and alcoholic beverages, and physical activity. Finally, we measured weight and height and calculated body mass index. RESULTS: The lipoperoxide levels were significantly higher in the postmenopausal group than in the premenopausal group (0.357 +/- 0.05 vs 0.331 +/- 0.05 MUmol/L, P = 0.001). Using logistic regression to control pro-oxidant variables, we found that menopause was the main risk factor for oxidative stress (odds ratio, 2.62; 95% CI, 1.35-5.11; P < 0.01). We also found a positive correlation between menopause rating score, insomnia score, and lipoperoxides, and this relationship was most evident in the postmenopausal group (menopause scale, r = 0.327 [P = 0.001]; insomnia scale, r = 0.209 [P < 0.05]). CONCLUSIONS: Our findings suggest that the depletion of estrogen in postmenopause could cause oxidative stress in addition to the known symptoms. PMID- 21971211 TI - Physical, psychological, and menopause-related symptoms and minor psychiatric disorders in a community-based sample of Brazilian premenopausal, perimenopausal, and postmenopausal women. AB - OBJECTIVE: The aim of this study was to identify the prevalence of physical, psychological, and menopause-related symptoms and their association with minor psychiatric disorders in premenopausal, perimenopausal, and postmenopausal women. METHODS: This was a nested cross-sectional study. Demographic characteristics, education, and climacteric symptoms were investigated. The 20-item Self-Reporting Questionnaire was used to screen for minor psychiatric disorders, with a score of 8 or higher indicating positive screening. RESULTS: We studied 324 Brazilian women aged 36 to 62 years (86 premenopausal women, 156 perimenopausal women, and 82 postmenopausal women). Mean (SD) age was 44.8 (3.6), 46.3 (4.6), and 53.3 (3.8) years, respectively (P < 0.001); 52.4% had 8 years or less of schooling (whereas 22.8% had 4 years or less). Forty-five (28.8%) perimenopausal women and 32 (39%) postmenopausal women were users of hormone therapy; 15 (17.4%) and 21 (13.5%) premenopausal and perimenopausal participants, respectively, were users of oral contraceptives. Hormone therapy and oral contraceptive users were excluded from the analysis of symptom prevalence. Hot flashes, night sweats, and vaginal dryness were more prevalent among perimenopausal women (P < 0.001). Fatigue was the most frequent complaint in all groups (61%, 81%, and 88% in premenopausal, perimenopausal, and postmenopausal women, respectively). The variables most frequently associated with positive findings during the screening for minor psychiatric disorders were very low education level and memory loss and irritability. Classic vasomotor complaints were weakly associated with nonpsychotic disease. In turn, perimenopausal women, but not postmenopausal women, were at greater risk of minor psychiatric disorders. CONCLUSIONS: Low education level, memory loss, irritability, and the menopausal transition represent risk factors for positive findings in a screening for minor psychiatric disorders. PMID- 21971212 TI - New aspects concerning to the characterization and the relationship with the immune response in vivo of the spiny lobster Panulirus argus nitric oxide synthase. AB - Nitric oxide (NO) is a short-lived radical generated by nitric oxide synthases (NOS). NO is involved in a variety of functions in invertebrates, including host defense. In a previous study, we isolated and sequenced for the first time the NOS gene from hemocytes of Panulirus argus, demonstrating the inducibility of this enzyme by lipopolysaccharide (LPS) in vitro. In the present work, lobster hemocytes and gills exposed to Escherichia coli O55:B5 LPS showed an increase in both NOS activity and NOS gene expression in vivo. This response was dose and time dependent. The 3D NOS structure was predicted by comparative modeling showing the oxygenase and reductase domains. These domains contain the conserved binding motifs of NOS already found in a variety of organisms. The 3D structure prediction analysis allowed the selection of a fragment of 666bp that was cloned and subsequently expressed in E. coli BL21, in which a recombinant product of around 31KDa was obtained. Hyperimmune serum obtained from immunized rabbits was tested and employed to specifically detect the recombinant polypeptide or the endogenous NOS from lobster hemocytes by western blot and immunofluorescence. This study contributes to enlarge the existing knowledge related to NOS structure and NOS participation in the immune response in lobsters. The evaluation of an antibody capable to recognize NOS from lobsters constitutes a novel and interesting tool for the implementation of further studies on NOS functions in crustaceans. PMID- 21971213 TI - Capsaicin instillation for postoperative pain following total knee arthroplasty: a preliminary report of a randomized, double-blind, parallel-group, placebo controlled, multicentre trial. AB - BACKGROUND: Pain following total knee arthroplasty (TKA) interferes with rehabilitation. Capsaicin applied in high concentration to nociceptors can cause relatively selective C-fibre desensitization for a period of weeks to months. Resultant long-lasting analgesia might facilitate rehabilitation. OBJECTIVE: The objective of this study was to determine if direct instillation of a high concentration capsaicin preparation into the wound following TKA would provide pain relief, improve physical functioning and rehabilitation, and reduce opioid requirements. METHODS: This was a randomized, double-blind, parallel-group, placebo-controlled, multicentre, phase II trial carried out in a teaching hospital system. Non-opioid-tolerant males or females aged 18-85 years with a body mass index (BMI) <=45 kg/m2, American Society of Anesthesiologists (ASA) physical status 1-3 and end-stage osteoarthritis who were scheduled for primary unilateral TKA were included. Patients received placebo vehicle or capsaicin 15 mg (Anesiva 4975) by instillation immediately prior to wound closure. Surgery was conducted under spinal anaesthesia and femoral nerve block. Postoperative rescue analgesia consisted of intravenous patient-controlled analgesia with morphine for 24 hours; oral oxycodone was provided thereafter as needed. It was hypothesized prior to data collection that capsaicin instillation would reduce postoperative pain scores and result in improved patient satisfaction and ambulation. The primary outcome was the area under the numerical rating scale (NRS) for pain score-time curve from 4 to 24 hours (AUC(4-24)). NRS for pain scores were obtained every 4 hours for 24 hours then daily with ambulation and physical therapy for 3 days. Function and patient satisfaction were assessed at 14, 28 and 42 days. RESULTS: Data from 14 patients (seven per group) from a single centre (data were not available from other sites because of sponsor bankruptcy) were available for this preliminary report. AUC(4-24) was not significantly different clinically (placebo 70.3; capsaicin 65.7) in this sample; however, a significant opioid-sparing effect was seen in the capsaicin group despite the fact that patients in this group had higher BMIs. Pain scores tended to be lower in the capsaicin group, despite the fact that patients in this group received significantly less rescue opioid medication. Morphine use from 12-24 hours was lower (capsaicin group mean 13.4 mg; 95% confidence interval [CI] 7.4, 19.5; range 10-21 mg vs placebo group mean 25.9 mg; 95% CI 19.8, 32.0; range 15-36 mg; p = 0.009). Total intravenous and oral opioid in morphine equivalents over 72 hours was also lower with capsaicin compared with placebo (p = 0.03). Active range of motion (ROM) was also significantly improved at day 14 in the capsaicin group compared with the placebo group (p = 0.0014). A higher percentage of patients in the capsaicin group reported being extremely satisfied with their treatment. The only statistically significant difference in treatment-emergent adverse events was for pruritus, which was more frequent in the placebo group (p = 0.03). CONCLUSION: Despite having higher BMIs, patients in the capsaicin group achieved comparable or better pain scores with significantly less opioid use in the first 3 postoperative days. They also had less pruritus, which may have been a consequence of the opioid-sparing effect. The effects of capsaicin with respect to function, however, appeared to be longer lasting, with improved active ROM reported at 14 days. PMID- 21971214 TI - FAS-670A/G single nucleotide polymorphism may be associated with human T lymphotropic virus-1 infection and clinical evolution to TSP/HAM. AB - FAS and FASLG genes are closely linked to the apoptosis mechanism of the immune system and several polymorphisms in these genes have been associated with susceptibility to diseases. The present study investigated the polymorphisms at positions -670 in the FAS gene, and -169 and -124 in the FASLG gene, among HTLV-1 infected subjects. Blood samples from HTLV infected subjects and seronegative individuals were collected, and polymorphisms were analyzed using a polymerase chain reaction (PCR) followed by RFLP analysis using restriction endonucleases. The genotype frequencies of the FAS -670 polymorphism was the only one that showed a higher and significant prevalence of genotype -670GG among HTLV-1 infected subjects as compared to the control group (p=0.0160), but the genotype 670AA was more frequent among TSP/HAM patients as compared to the asymptomatic individuals (p=0.0005). TCD4(+) and TCD8(+) lymphocyte counts from HTLV infected and seronegative subjects, as well as the proviral load values, according to the status of symptomatic and asymptomatic infection carrying different genotypes were compared but showed no statistical significance. The present results suggest that FAS -670 polymorphism seems to be associated with susceptibility to HTLV-1 and may increase the chance to develop TSP/HAM among HTLV-1 infected persons. PMID- 21971215 TI - Sequential administration of bovine and human adenovirus vectors to overcome vector immunity in an immunocompetent mouse model of breast cancer. AB - The potential of a bovine adenovirus serotype 3 (BAd3)-based vector to bypass the human adenoviral serotype 5 (HAd5)-specific neutralizing immune response was evaluated in an immunocompetent mouse model of breast cancer. Initially we monitored vector biodistribution, genome persistence, transgene expression, and potential toxicity of HAd-GFP [HAd5 vector expressing green fluorescent protein (GFP)] or BAd-GFP (BAd3 vector expressing GFP) in FVB/n mice bearing tumors. A comparable biodistribution pattern for BAd-GFP and HAd-GFP was evident. In addition, following the development of vector-specific immune responses, animals were inoculated intratumorally (i.t.) with HAd-GFP or BAd-GFP. HAd-GFP immunity did not hamper the transduction and persistence of BAd-GFP into the tumors and other organs, and, similarly, BAd-GFP immunity did not hamper the transduction and persistence of HAd-GFP. Both BAd3 and HAd5 vectors showed relatively higher transgene expression in the presence of heterologous vector immunity. In contrast, the homologous vector immunity was associated with a rapid vector clearance and decline in transgene expression levels. Histopathological changes in BAd-GFP inoculated animals were generally mild with some acute but recoverable hepatic perturbations. Overall, the data suggest the importance of BAd3 vectors for sequential vector administration in overcoming the vector immunity for cancer gene therapy. PMID- 21971216 TI - [Management of viral infections after allogeneic hematopoietic stem cell transplantation]. PMID- 21971217 TI - [Guidelines for febrile neutropenia]. PMID- 21971218 TI - [Current problems on the management of HTLV-1 asymptomatic carriers and ATL patients]. PMID- 21971219 TI - [Anti-HTLV-1 task force by the Prime Minister of Japan and his cabinet: New government policy against HTLV-1/ATL]. PMID- 21971220 TI - [Recent status of the clinical trials and recruitment of patient enrollment in ATL]. PMID- 21971221 TI - [Risk factors and pathogenesis in thrombophilia]. PMID- 21971222 TI - [DVT prophylaxis for medical patients]. PMID- 21971223 TI - [Management of ambulatory chemotherapy for hematological malignancies]. PMID- 21971224 TI - [Developmental status of new drugs for malignant lymphomas in Japan]. PMID- 21971225 TI - [Treatment of multiple myeloma by immunomodulatory drugs]. PMID- 21971226 TI - [Recent advance in the treatment of AL amyloidosis and POEMS syndrome]. PMID- 21971227 TI - [Treatment strategy of aplastic anemia based on the pathophysiology of individual patients]. PMID- 21971228 TI - [Novel therapeutics for paroxysmal nocturnal hemoglobinuria]. PMID- 21971229 TI - [Molecular pathogenesis of MDS]. PMID- 21971230 TI - [Novel therapeutics for myelodysplastic syndromes]. PMID- 21971232 TI - [Progress of pathophysiology and therapeutic evidence in AML]. PMID- 21971231 TI - [Progress and problems in transfusion medicine]. PMID- 21971233 TI - [Hematopoietic stem cell transplantation for adult acute myeloblastic leukemia]. PMID- 21971234 TI - [Classification for myeloproliferative neoplasms and function of novel mutations]. PMID- 21971235 TI - [Standard therapy and current research topics for childhood/adolescent acute lymphoblastic leukemia]. PMID- 21971236 TI - [Current management of adult acute lymphoblastic leukemia/lymphoma]. PMID- 21971237 TI - [Current status and future perspective in imatinib therapy against CML]. PMID- 21971238 TI - [Roles of the 2nd generation TKIs for CML]. PMID- 21971239 TI - [Diagnostic key points and recent researches on the indolent B-cell lymphomas]. PMID- 21971240 TI - [Recent advances in the management of follicular lymphoma]. PMID- 21971241 TI - [Point of diagnosis and treatment of extranodal diffuse large B-cell lymphoma]. PMID- 21971243 TI - [Cancer genome defined by the next generation sequencers]. PMID- 21971242 TI - [Treatment of Burkitt lymphoma and Burkitt-like lymphoma]. PMID- 21971244 TI - [Cell cycle]. PMID- 21971245 TI - [Apoptosis and non-apoptotic cell death]. PMID- 21971246 TI - [Signaling pathways regulating hematopoiesis and their roles in hematopoietic malignancies]. PMID- 21971247 TI - [Epigenome in hematopoietic malignancies]. PMID- 21971248 TI - [How to read clinical trial reports]. PMID- 21971249 TI - [Science and ethics in clinical research]. PMID- 21971250 TI - [Basic and clinical research on HIV-1]. PMID- 21971251 TI - [The cutting edge of antitumor adoptive cell therapy]. PMID- 21971252 TI - [Advanced medical care system, highly advanced medical technology assessment system, and investigator-initiated registration-directed clinical trial]. PMID- 21971254 TI - [Genomic alterations in malignant lymphoma]. PMID- 21971253 TI - [IgG4-related disease-a novel disease concept-]. PMID- 21971255 TI - [Radiation injury to human body: atomic bombs, Chernobyl and Fukushima]. PMID- 21971257 TI - Spectral presaturation inversion recovery MR imaging sequence after gadolinium injection to differentiate fibrotic scar tissue and neoplastic strands in the mesorectal fat in patients undergoing restaging of rectal carcinoma after neoadjuvant chemo- and radiation therapy. AB - RATIONALE AND OBJECTIVES: To retrospectively assess the value of spectral presaturation by inversion-recovery (SPIR) magnetic resonance (MR) imaging sequence after gadolinium injection to differentiate fibrotic scar tissue and tumoral infiltration within the mesorectal fat in patients with rectal carcinoma undergoing MR restaging after neoadjuvant chemo- and radiation therapy (CRT). MATERIALS AND METHODS: Forty-three consecutive patients (mean age, 65.8 years; range, 46-85 years; male:female, 29:14) with locally advanced rectal carcinoma underwent CRT followed by surgery. MR imaging was performed before and after completion of CRT by using T2-weighted turbo spin-echo and T1-weighted SPIR sequences before and after gadolinium injection, and MR images were assessed by two radiologists in consensus. Logistic regression was conducted to test the significance of the MR image findings with histology. RESULTS: After CRT the disease was either limited to the rectal wall (n = 18 patients) or presented perirectal infiltration (n = 25) on histology. In 21 patients, mesorectal enhancing strands were observed. Reticular-shaped enhancing strands reaching the mesorectal fascia presented the highest correlation with tumor infiltration of the mesorectal fat (OR 130.33, 95% CI: 4.1-4220.29; logistic regression), whereas linear-shaped enhancing strands either reaching or not reaching the mesorectal fascia (OR 0.25 or 0.1, 95% CI: 0.024-2.6 or 0.01-1.07) revealed the lowest correlation. CONCLUSIONS: Reticular-shaped enhancing strands on SPIR MR imaging after gadolinium injection are associated with tumor infiltration of the mesorectal fat. PMID- 21971258 TI - Defining the intra-subject variability of whole-lung CT densitometry in two lung cancer screening trials. AB - RATIONALE AND OBJECTIVES: To define a statistically based variation of individual whole-lung densitometry above which a real increase of pulmonary extent can be suspected in lung cancer screening trials. MATERIALS AND METHODS: Baseline and 3 month follow-up low-dose computed tomography (LDCT) examinations of 131 smokers or former smokers recruited in the ITALUNG (32 subjects) and MILD (99 subjects) trials were compared using for each data set two different image processing tools for whole-lung densitometry. Both trials were approved by institutional review boards, and written informed consent was obtained from all participants. Assuming that no change of emphysema extent can occur in a 3-month interval, the Bland and Altman method was used to assess the agreement between baseline and follow-up LDCT examinations for lung volume, 15th percentile (Perc15) of lung density and Perc15 corrected for lung volume by application of a linear detrend on log transformed data. RESULTS: Similar results were obtained in each data set using two different image processing tools. In the ITALUNG cohort the 95% limits of agreement (LoA) interval of volume corrected Perc15 was -9.7 to 10.7% using image processing method 1 and -10.3 to 11.5% using image processing method 2. In the MILD cohort, the 95% LoA interval of volume corrected Perc15 was -14.7 to 17.3% with both image processing methods. CONCLUSION: In the two considered lung cancer screening settings a range of 9.7-14.7% decrease of volume corrected Perc15 represents a statistically defined threshold to suspect a real increase of emphysema extent in serial LDCT examinations. PMID- 21971256 TI - Disposition of ultrasound sensitive polymeric drug carrier in a rat hepatocellular carcinoma model. AB - RATIONALE AND OBJECTIVES: A doxorubicin-loaded microbubble has been developed that can be destroyed with focused ultrasound resulting in fragments, or "nanoshards" capable of escaping through the leaky tumor vasculature, promoting accumulation within the interstitium. This study uses a rat liver cancer model to examine the biodistribution and tumoral delivery of this microbubble platform compared with de novo drug-loaded polymer nanoparticles and free doxorubicin. MATERIALS AND METHODS: Microbubbles (1.8 MUm) and 217-nm nanoparticles were prepared containing 14-C labeled doxorubicin. Microbubbles, nanoparticles, a combination of the two, or free doxorubicin were administered intravenously in rats bearing hepatomas, concomitant with tumor insonation. Doxorubicin levels in plasma, organs, and tumors were quantified after 4 hours and 7 and 14 days. Tumors were measured on sacrifice and evaluated with autoradiography and histology. RESULTS: Animals treated with microbubbles had significantly lower plasma doxorubicin concentrations (0.466 +/- 0.068%/mL) compared with free doxorubicin (3.033 +/- 0.612%/mL, P = .0019). Drug levels in the myocardium were significantly lower in animals treated with microbubbles compared to free doxorubicin (0.168%/g tissue vs. 0.320%/g, P = .0088). Tumors treated with microbubbles showed significantly higher drug levels than tumors treated with free doxorubicin (2.491 +/- 0.501 %/g vs. 0.373 +/- 0.087 %/g, P = .0472). These tumors showed significantly less growth than tumors treated with free doxorubicin (P = .0390). CONCLUSIONS: Doxorubicin loaded microbubbles triggered with ultrasound provided enhanced, sustained drug delivery to tumors, reduced plasma and myocardium doxorubicin levels, and arresting tumor growth. The results suggest that in situ generation of nano particles provides a superior treatment over injection of free drug and also de novo synthesized nanoparticles. PMID- 21971259 TI - An observer study for a computer-aided reading protocol (CARP) in the screening environment for digital mammography. AB - RATIONALE AND OBJECTIVES: The aims of this study were to investigate improving work flow efficiency by shortening the reading time of digital mammograms using a computer-aided reading protocol (CARP) in the screening environment and to increase detection sensitivity using CARP, compared to the current protocol, commonly referred to as the quadrant view (QV). MATERIALS AND METHODS: A total of 200 cases were selected for a receiver-operating characteristic (ROC) study to evaluate two image display work flows, CARP and QV, in the screening environment. A Web-based tool was developed for scoring, reporting, and statistical analysis. Cases were scored for and stratified by difficulty. A total of six radiologists of differing levels of training ranging from dedicated mammographers to senior radiology residents participated. Each was timed while interpreting the 200 cases in groups of 50, first using QV and then, after a washout period, using CARP. The data were analyzed using ROC and kappa analysis. Interpretation times were also assessed. RESULTS: Using QV, readers' average area under the ROC curve was 0.68 (range, 0.54-0.73). Using CARP, readers' average area under the ROC curve was 0.71 (range, 0.66-0.75). There was no statistically significant difference in reader performance using either work flow. However, there was a statistically significant reduction in the average interpretation time of negative cases from 64.7 seconds using QV to 58.8 seconds using CARP. CONCLUSIONS: CARP determines the display order of regions of interest depending on computer-aided detection findings. This is a variation of traditional computer-aided detection for digital mammography that has the potential to reduce interpretation times of studies with negative findings without significantly affecting sensitivity, thus allowing improved work flow efficiency in the screening environment, in which, in most settings, the majority of cases are negative. PMID- 21971261 TI - Educating radiology residents in the new era: implementation and evaluation of online end-of-rotation examinations. AB - RATIONALE AND OBJECTIVES: The aim of this report is to describe preliminary experience with an educational tool implemented to improve radiology education and documentation, in anticipation of upcoming changes from the American Board of Radiology and the Accreditation Council for Graduate Medical Education. MATERIALS AND METHODS: Monthly online end-of-rotation examinations were developed for junior radiology residents. Examinations were administered over a period of 6 months, after which satisfaction surveys were administered to residents and faculty members. RESULTS: Satisfaction with end-of-rotation examinations was high for residents and faculty members, but the level of resident satisfaction was not statistically different when compared to that of residents who had taken fewer examinations. CONCLUSIONS: End-of-rotation examinations are relatively straightforward to implement and facilitate recurring, structured, and meaningful resident evaluation and feedback. Future studies will explore whether examinations such as these result in improved clinical competency. PMID- 21971260 TI - Full field digital mammography and breast density: comparison of calibrated and noncalibrated measurements. AB - RATIONALE AND OBJECTIVES: Mammographic breast density is an important and widely accepted risk factor for breast cancer. A statement about breast density in the mammographic report is becoming a requirement in many States. However, there is significant inter-observer variation between radiologists in their interpretation of breast density. A properly designed automated system could provide benefits in maintaining consistency and reproducibility. We have developed a new automated and calibrated measure of breast density using full field digital mammography (FFDM). This new measure assesses spatial variation within a mammogram and produced significant associations with breast cancer in a small study. The costs of this automation are delays from advanced image and data analyses before the study can be processed. We evaluated this new calibrated variation measure using a larger dataset than previously. We also explored the possibility of developing an automated measure from unprocessed (raw data) mammograms as an approximation for this calibrated breast density measure. MATERIALS AND METHODS: A case-control study comprised of 160 cases and 160 controls matched by age, screening history, and hormone replacement therapy was used to compare the calibrated variation measure of breast density with three variants of a noncalibrated measure of spatial variation. The operator-assisted percentage of breast density measure (PD) was used as a standard reference for comparison. Odds ratio (OR) quartile analysis was used to compare these measures. Linear regression analysis was applied to assess the calibration's impact on the raw pixel distribution. RESULTS: All breast density measures showed significant breast cancer associations. The calibrated spatial variation measure produced the strongest associations (OR: 1.0 [ref.], 4.6, 4.3, 7.4). The associations for PD were diminished in comparison (OR: 1.0 [ref.], 2.7, 2.9, 5.2). Two additional non calibrated measures restricted in region size also showed significant associations (OR: 1.0 [ref.], 2.9, 4.4, 5.4), and (OR: 1.0 [ref.], 3.5, 3.1, 4.9). Regression analyses indicated the raw image mean is influenced by the calibration more so than its standard deviation. CONCLUSION: Breast density measures can be automated. The associated calibration produced risk information not retrievable from the raw data representation. Although the calibrated measure produced the stronger association, the non-calibrated measures may offer an alternative to PD and other operator based methods after further evaluation, because they can be implemented automatically with a simple processing algorithm. PMID- 21971262 TI - Saving manuscripts. PMID- 21971263 TI - Cardiac outflow and wall motion in hypothermic chick embryos. AB - Cardiac outflow in the early developmental stage of a chick embryo is known to be highly variable depending on environmental temperature. To investigate the effects of environmental hypothermia on the blood flow in the outflow tract (OFT) of chick embryonic hearts, microscopic flow images were consecutively captured from chick embryos at HH stage 17 (2.5 days of incubation) at room temperature. Instantaneous velocity field information of blood flow in OFT was obtained using a micro-particle image velocimetry technique. The cyclic variations of the OFT vessel diameter and wall thickness were simultaneously measured. The experimental results show that environmental hypothermia causes bradycardia with a decrease in peak velocity during systole and the occurrence of backflow during diastole in the OFT. These abnormal phenomena seem to be attributed to the suppression of myocardial wall motion under hypothermic conditions. PMID- 21971264 TI - Phase stabilization in nitrogen-implanted nanocrystalline cubic zirconia. AB - The phase stability of nanocrystallites with metastable crystal structures under ambient conditions is usually attributed to their small grain size. It remains a challenging problem to maintain such phase integrity of these nanomaterials when their crystallite sizes become larger. Here we report an experimental-modelling approach to study the roles of nitrogen dopants in the formation and stabilization of cubic ZrO(2) nanocrystalline films. Mixed nitrogen and argon ion beam assisted deposition (IBAD) was applied to produce nitrogen-implanted cubic ZrO(2) nanocrystallites with grain sizes of 8-13 nm. Upon thermal annealing, the atomic structure of these ZrO(2) films was observed to evolve from a cubic phase, to a tetragonal phase and then a monoclinic phase. Our X-ray absorption near edge structure study on the annealed samples together with first-principle modelling revealed the significance of the interstitial nitrogen in the phase stabilization of nitrogen implanted cubic ZrO(2) crystallites via the soft mode hardening mechanism. PMID- 21971265 TI - Hierarchical carbon nanostructure design: ultra-long carbon nanofibers decorated with carbon nanotubes. AB - Hierarchical carbon nanostructures based on ultra-long carbon nanofibers (CNF) decorated with carbon nanotubes (CNT) have been prepared using plasma processes. The nickel/carbon composite nanofibers, used as a support for the growth of CNT, were deposited on nanopatterned silicon substrate by a hybrid plasma process, combining magnetron sputtering and plasma-enhanced chemical vapor deposition (PECVD). Transmission electron microscopy revealed the presence of spherical nanoparticles randomly dispersed within the carbon nanofibers. The nickel nanoparticles have been used as a catalyst to initiate the growth of CNT by PECVD at 600 degrees C. After the growth of CNT onto the ultra-long CNF, SEM imaging revealed the formation of hierarchical carbon nanostructures which consist of CNF sheathed with CNTs. Furthermore, we demonstrate that reducing the growth temperature of CNT to less than 500 degrees C leads to the formation of carbon nanowalls on the CNF instead of CNT. This simple fabrication method allows an easy preparation of hierarchical carbon nanostructures over a large surface area, as well as a simple manipulation of such material in order to integrate it into nanodevices. PMID- 21971266 TI - Porcine xenograft biosynthetic wound dressings for the management of postoperative Mohs wounds. AB - Cadaveric allografts and a large variety of other biologic dressings have been reported as being useful for the postoperative management of Mohs micrographic surgery (MMS) wounds. Although the use of porcine xenografts for the immediate postoperative management of these wounds is known, their use has not been detailed in the dermatology literature. A case series of 15 consecutive Mohs micrographic surgery patients (mean age = 74.9 years, range = 49 to 89 years) with wounds initially managed with porcine xenografts is described. Porcine xenografts were useful in a variety of clinical settings following MMS. These included: (1) wound management when tumor margins were indeterminate pending additional dermatopathology studies and (2) wound management when there are issues such as through and through nasal defects involving the mucosa, large wound depth, exposed cartilage and or bone, or patient medical comorbidities that delay or prevent plans for immediate wound reconstruction. Future controlled studies of biologic dressings are needed to determine which options are best for micrographic surgery wounds. Comparisons should also include the traditional option of second intention healing without biologic dressings. PMID- 21971267 TI - A case of cutaneous protothecosis in a polyarteritis nodosa patient and review of cases reported in Japan. AB - A 76-year-old woman farmer with a 20-year history of oral steroid treatment for polyarteritis nodosa, noted a rash consisting of numerous small papules on the dorsum of her right hand in February 2007. The rash worsened over time, and in April 2008 red papules and pustules as big as grains of rice fused to form plaques extending up her arm from the dorsum of the right hand to the extensor surface of the forearm. The plaques were accompanied by erosions, ulcers, and crusts. Skin biopsy specimens from the dorsum of the right hand showed a dense cell infiltration in the upper to middle layer of the dermis, with numerous morula-like microorganisms within the cells. Cultures of the specimens on Sabouraud dextrose agar produced creamy, yeast-like colonies. The colonies produced sporangia, with cells of varying sizes arranged in the pattern of a spoked-wheel. The microorganisms were identified as Prototheca wickerhamii on the basis of their morphological characteristics, sugar assimilation patterns, and molecular biological techniques. Treatment with amphotericin B was planned, but the patient died from respiratory failure before initiating treatment. We review the characteristics of the cutaneous protothecosis cases reported to date in Japan. PMID- 21971268 TI - Unilateral calciphylaxis in a patient with systemic lupus erythematosus, chronic kidney disease, and hemodialysis-associated steal syndrome. AB - Calciphylaxis is a rare but life-threatening disease characterized by deposition of calcium within small and medium sized vessels, with subsequent thrombosis, cutaneous ischemia, and necrosis. Because of its systemic nature, calciphylaxis is typically a symmetrical, bilaterally-distributed phenomenon. Here, we present an unusual case of unilateral leg calciphylaxis in the setting of relative chronic arterial insufficiency of the affected extremity secondary to steal syndrome. PMID- 21971269 TI - Rapid clinical change in lesions of atypical cutaneous lymphoproliferative disorder in an HIV patient: a case report and review of the literature. AB - BACKGROUND: HIV associated atypical cutaneous lymphoproliferative disorder (ACLD) is a rare condition characterized by a pruritic, often generalized, eruption of patches and plaques or erythroderma clinically simulating mycosis fungoides (MF) or Sezary syndrome. A polyclonal CD8+ T-cell infiltrate on biopsy can help differentiate ACLD from MF or Sezary syndrome, but the clinical and histopathologic appearance must also be considered. Accurate diagnosis is imperative because HAART therapy has been reported to improve this condition in some patients. OBSERVATION: We report a case of HIV associated ACLD, with an atypical presentation, initially consisting of diffuse papules, some with a dusky targetoid center. Two weeks after starting antiviral therapy the papules flattened, evolving to xerotic, hyperpigmented macules. CONCLUSION: The working theory of a reactive etiology for this condition might explain the evolution in appearance following initiation of HAART. The presence of papules with a dusky targetoid center suggests that this condition should be considered in the differential diagnosis with syphilis or atypical erythema multiforme in HIV patients. PMID- 21971270 TI - Malignant chondroid syringoma: report of a case with lymph node metastasis 12 years after local excision. AB - A 46-year-old man noticed a nodule on his sole. The nodule was removed and the specimen showed a lobular proliferation of tumor cells with glandular differentiation embedded in mucinous stroma. A diagnosis of chondroid syringoma was made. Twelve years later, he noted a swelling in the right inguinal region. The mass was surgically removed. The histopathological findings of the lymph node showed the more atypical tumor cells in the mucoid stroma. Upon reexamination, the primary tumor contained malignant chondroid syringoma (MCS) cells; the tumor cells metastasized to lymph node. MCS is rare with 43 reported cases in the literature. The site of the primary tumor was the lower extremity in 35 percent, the head in 28 percent, and the upper extremity in 23 percent. The percentage of malignant cases with local recurrence, nodal metastasis, and distant metastasis was 49 percent, 42 percent, and 40 percent, respectively. In these cases, the average time period until disease recurrence was 23 months, 50 months, and 66 months for local recurrence, nodal metastasis, and distant metastasis, respectively. Of these, 23 percent of the cases succumbed. As MCS may progress very slowly and disease recurrence including metastasis occurs in a relatively high percentage of cases, long-term follow-up of MCS cases is required. PMID- 21971271 TI - [Uncommon causes of leg ulcers: investigative approach and therapeutics]. AB - Chronic wounds of the lower limbs are a major public healthcare problem affecting 1 percent of the adult population and 3 to 5 percent of people older than 65 years. These numbers are rising in the western population as a result of increased life expectancy and increased risk factors for atherosclerotic occlusion, such as smoking, obesity, and diabetes mellitus. This very debilitating condition, which reduces significantly the quality of life, causes social discomfort and generates considerable cost, not only to the patient but also to the society. Treating chronic leg ulcers is always a challenge. Over the last years, the treatment of this condition has been given more attention because of the frequent ineffectiveness of the methods used, the awareness of the psychological and social impact, and the recognition of the risks of malignancy in these wounds. Determining the etiology is an essential factor for directed and more effective wound care. Although 90 percent of ulcers are of vascular origin, the list of other possible causes responsible for the other 10 percent is extremely long. In this review, the authors focus on the differential diagnosis of chronic leg ulcers and the impact of directed treatment in the prognosis of this condition. PMID- 21971272 TI - Leukemia cutis in B-cell chronic lymphocytic leukemia presenting as an episodic papulovesicular eruption. AB - A 53-year-old man presented with a recurrent pruritic eruption accompanied by oral sores. His past medical history was significant for subclinical B-cell chronic lymphocytic leukemia (CLL), which had never been treated. On exam, there were erythematous papules and plaques studded with vesicles on the neck, trunk, and upper extremities. Two skin biopsies showed common features of a perivascular and periadnexal lymphocytic infiltrate in the superficial to mid-dermis. Immunohistochemical staining of the lymphocytes showed co-expression of CD20, CD23, CD5, and CD43, consistent with a diagnosis of cutaneous involvement by the patient's CLL. This case highlights the importance of considering leukemia cutis in patients with underlying CLL presenting with unusual clinical features. PMID- 21971273 TI - Hypocellular medallion-like dermal dendrocyte hamartoma (plaque-like CD34 positive dermal fibroma). AB - Medallion-like dermal dendrocyte hamartoma (MLDDH) is a recently described congenital dermal neoplasm. Only 11 cases have been reported in the English literature and therefore its clinical and pathological manifestations are not completely defined. We report the case of a 20-year-old male presenting with a round, erythematous, atrophic plaque on the midline of the anterior aspect of the neck. The lesion was asymptomatic and was stable since birth. A skin biopsy was performed. Histological examination showed a band like hypocellular fibrotic area in the superficial reticular dermis, which did not spread to subcutaneous tissue. The cells were CD34-positive and S100 and CD56-negative. Elastic fibers were present. Altogether the morphological and immunostaining features were neither suggestive of dermatofibrosarcoma protuberans nor neurofibroma. Thus, the pathological findings were consistent with MLDDH. Clinical differential diagnosis includes anetoderma, aplasia cutis, or atrophic DFSP. Histological differential was made with atrophic scar and striae distensae. Although the histological findings were not identical to those described recently as characteristic, the clinical features were suggestive enough to make the diagnosis of MLDDH. Therefore in our experience, the MLDDH spectrum might include lesions with variable cellular density, which can show similar clinical manifestations. PMID- 21971274 TI - Zosteriform B-cell chronic lymphocytic leukemia infiltration. AB - Cutaneous infiltration by leukemic cells is uncommon and may be associated with progression of disease. The authors present the case of a 77-year-old female patient, referred to the dermatology clinic for red, erythematous, pruritic papules, which had suddenly appeared on her left hemithorax, along the C6 dermatome, with a 4-week duration. She had already been medicated with Valacyclovir and Acyclovir for 4 weeks, without clinical improvement. She also had a diagnosis of B-cell chronic lymphocytic leukemia (B-CLL), type 2 diabetes mellitus, and multinodular goiter. Tzanck smear showed no multinucleated giant cells,and PCR testing for Varicella Zoster Virus (VZV) and Herpes Simplex Virus (HSV) on skin biopsy was negative. Histopathology showed a typical B-CLL infiltrate (CD3+, CD20+) and cytogetic analysis was compatible with alterations seen in the bone marrow, confirming the diagnosis of cutaneous infiltration by B CLL. The patient began chemotherapy with chlorambucil and intravenous human immunoglobulin, which resulted in total regression of the lesions as well as the pruritus. Even though lymphocytic infiltration of Herpes Simplex or Herpes Zoster scars is well documented, cutaneous infiltration with a zosteriform distribution without a previous episode of herpes is very rare. The therapeutic target should be the leukemia itself. PMID- 21971275 TI - Porokeratotic eccrine ostial and dermal duct nevus treated with a combination erbium/CO2 laser: a case and brief review. AB - Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is an uncommon disease that presents early in childhood and is characterized by keratotic papules, often in a linear configuration. We describe a 12-year-old girl with characteristic lesions of PEODDN and describe her response to treatment with a combination CO2/Erbium laser. We also briefly review the literature on PEODDN. PMID- 21971276 TI - Angiokeratoma circumscriptum naeviforme: a case report of a rare disease. AB - Angiokeratomas are relatively rare vascular lesions characterized by ectasias of the papillary dermal blood vessels with secondary epidermal changes in the form of acanthosis and/or hyperkeratosis. Amongst the several variants of angiokeratomas, angiokeratoma circumscriptum is the least common one. Angiokeratoma circumscriptum naeviforme (ACN) is a still rarer type of angiokeratoma, which is typically seen at birth. We report here a case of linear, unilateral, verrucous plaques on the leg of a young man, diagnosed as ACN. PMID- 21971277 TI - Painful growth on right index finger. Subungual glomus tumor. AB - Glomus tumors (GT) are rare, soft-tissue tumors commonly found on the extremities. Because these tumors occur most often in the subungual region, they can be confused with other subungual pathologies including melanoma. Subungual GTs have a unique presentation and history but biopsy is diagnostic. Various imaging techniques are useful in diagnosis and management. We describe a classical case of subungual GT and discuss its presentation, diagnosis, management, as well as "atypical" or "malignant" variants. PMID- 21971278 TI - Ulcerated infantile hemangioma treated with imiquimod. AB - A 5-month-old boy was observed in our department presenting with an ulcerated infantile hemangioma on the right buttock. This lesion appeared during the first week of life and had been growing progressively, showing ulceration for 3 weeks. We started treatment with corticosteroids, first with the association of betametasone and fusidic acid topically, and then systemically. After 6 weeks of oral treatment as there was no significant improvement, corticosteroid therapy was slowly tapered and local application of imiquimod 5 percent cream, on alternate days, was started. After 12 weeks of therapy with imiquimod there was complete resolution of the ulceration. There were no side effects. PMID- 21971279 TI - Letter: Neutrophilic eccrine hidroadenitis with atypical findings. AB - Neutrophilic eccrine hidradenitis (NEH) was originally described as a distinctive dermatosis occurring in patients undergoing chemotherapy, especially associated with the use of cytarabine in the treatment of acute myelogenous leukemia (AML). This disorder is characterized by a neutrophilic infiltrate around the eccrine glands and coils and is associated with necrosis. However, atypical findings in the histology have been reported. To the best of our knowledge, leukocytoclastic vasculitis has not been described in association with NEH. We hypothesize that a toxic effect of cytarabine may damage the vessel wall to some extent, causing a vasculitic phenomenon. PMID- 21971280 TI - New-onset psoriasis associated with adalimumab: a report of two cases. AB - TNF-alpha inhibitors, including adalimumab, are increasingly used in the management of inflammatory cutaneous, gastrointestinal, and rheumatologic diseases. An untoward class effect of these medications is the development of new onset psoriasis, particularly in patients treated for rheumatologic diseases without any personal or family history of cutaneous psoriasis. We report two patients that developed cutaneous and histologic changes consistent with psoriasis while receiving treatment with adalimumab for inflammatory arthridities: one patient with Crohn disease and ankylosing spondylitis who tolerated adalimumab for 15 months before developing psoriasis and another patient with rheumatoid arthritis who developed psoriasis 3 years after starting adalimumab. Both patients experienced rapid resolution of their psoriasis after discontinuation of adalimumab. PMID- 21971281 TI - Regioselectivity control of graphene functionalization by ripples. AB - Ripples naturally occur in graphene sheets. First-principles calculations reveal that, by altering the pyramidalization angles of the carbon atoms, these ripples can be used to direct the chemical reactivity of graphene towards hydrogenation. A fraction of the carbon atoms of a rippled graphene, located around the crests and troughs, show significantly increased reactivity. The remaining carbon atoms have comparable reactivity to those in a flat graphene. To illustrate the increased reactivity, we show that hydrogenation becomes exothermic when the characteristic ratio between the amplitude and wavelength reaches ~0.55. This finding offers a practical chemical venue for regioselectivity control of graphene functionalization. While the rippling does not directly affect the band gap of the graphene, the rippling-induced hydrogenation does. PMID- 21971284 TI - Connective tissue diseases: Immune responses in Mikulicz disease differ from those in SS. PMID- 21971283 TI - Screening: FRAX in clinical practice. PMID- 21971285 TI - Connective tissue diseases: Predicting death in SSc: planning and cooperation are needed. PMID- 21971286 TI - Biochemical signatures of in vitro radiation response in human lung, breast and prostate tumour cells observed with Raman spectroscopy. AB - This work applies noninvasive single-cell Raman spectroscopy (RS) and principal component analysis (PCA) to analyze and correlate radiation-induced biochemical changes in a panel of human tumour cell lines that vary by tissue of origin, p53 status and intrinsic radiosensitivity. Six human tumour cell lines, derived from prostate (DU145, PC3 and LNCaP), breast (MDA-MB-231 and MCF7) and lung (H460), were irradiated in vitro with single fractions (15, 30 or 50 Gy) of 6 MV photons. Remaining live cells were harvested for RS analysis at 0, 24, 48 and 72 h post irradiation, along with unirradiated controls. Single-cell Raman spectra were acquired from 20 cells per sample utilizing a 785 nm excitation laser. All spectra (200 per cell line) were individually post-processed using established methods and the total data set for each cell line was analyzed with PCA using standard algorithms. One radiation-induced PCA component was detected for each cell line by identification of statistically significant changes in the PCA score distributions for irradiated samples, as compared to unirradiated samples, in the first 24-72 h post-irradiation. These RS response signatures arise from radiation induced changes in cellular concentrations of aromatic amino acids, conformational protein structures and certain nucleic acid and lipid functional groups. Correlation analysis between the radiation-induced PCA components separates the cell lines into three distinct RS response categories: R1 (H460 and MCF7), R2 (MDA-MB-231 and PC3) and R3 (DU145 and LNCaP). These RS categories partially segregate according to radiosensitivity, as the R1 and R2 cell lines are radioresistant (SF(2) > 0.6) and the R3 cell lines are radiosensitive (SF(2) < 0.5). The R1 and R2 cell lines further segregate according to p53 gene status, corroborated by cell cycle analysis post-irradiation. Potential radiation-induced biochemical response mechanisms underlying our RS observations are proposed, such as (1) the regulated synthesis and degradation of structured proteins and (2) the expression of anti-apoptosis factors or other survival signals. This study demonstrates the utility of RS for noninvasive radiobiological analysis of tumour cell radiation response, and indicates the potential for future RS studies designed to investigate, monitor or predict radiation response. PMID- 21971287 TI - Potential role of Mycoplasma hominis in interleukin (IL)-17-producing CD4+ T-cell generation via induction of IL-23 secretion by human dendritic cells. AB - BACKGROUND: Mycoplasma hominis, a human urogenital pathogen, is involved in genital and extragenital infections and arthritis, particularly in immunocompromised patients. The interleukin (IL) 23/T helper (Th) 17 axis is associated with inflammatory and autoimmune diseases. The aim of this study was to assess the IL-23 response to M. hominis in human dendritic cells (DCs) and the CD4(+) T-cell differentiation in response to M. hominis-infected DCs. METHODS: Human monocyte-derived DCs were cultured with phosphate-buffered saline, lipopolysaccharide, or M. hominis PG21. Cocultures with heterologous T cells were performed. Extracts from M. hominis were separated and incubated with DCs. Isolates from different clinical syndromes were tested. RESULTS: M. hominis induced the maturation of human DCs with predominant IL-23 secretion in a Toll like receptor 2-dependent manner. The in vitro immunomodulatory capacity of M. hominis was contained in a lipoprotein-enriched fraction from the mycoplasma. M. hominis-activated DCs induced IL-17-producing CD4(+) T cells. Interestingly, clinical isolates differed in their ability to promote IL-23 secretion by DCs. CONCLUSIONS: Taken together, our findings demonstrate a major role for the IL 23/Th17 axis in the defense against M. hominis and indicate a potential role for these bacteria in inflammatory and autoimmune diseases. PMID- 21971288 TI - Neuroblastoma therapy: what is in the pipeline? AB - Despite the expansion of knowledge about neuroblastoma (NB) in recent years, the therapeutic outcome for children with a high-risk NB has not significantly improved. Therefore, more effective therapies are needed. This might be achieved by aiming future efforts at recently proposed but not yet developed targets for NB therapy. In this review, we discuss the recently proposed molecular targets that are in clinical trials and, in particular, those that are not yet explored in the clinic. We focus on the selection of these molecular targets for which promising in vitro and in vivo results have been obtained by silencing/inhibiting them. In addition, these selected targets are involved at least in one of the NB tumorigenic processes: proliferation, anti-apoptosis, angiogenesis and/or metastasis. In particular, we will review a recently proposed target, the microtubule-associated proteins (MAPs) encoded by doublecortin-like kinase gene (DCLK1). DCLK1-derived MAPs are crucial for proliferation and survival of neuroblasts and are highly expressed not only in NB but also in other tumours such as gliomas. Additionally, we will discuss neuropeptide Y, its Y2 receptor and cathepsin L as examples of targets to decrease angiogenesis and metastasis of NB. Furthermore, we will review the micro-RNAs that have been proposed as therapeutic targets for NB. Detailed investigation of these not yet developed targets as well as exploration of multi-target approaches might be the key to a more effective NB therapy, i.e. increasing specificity, reducing toxicity and avoiding long-term side effects. PMID- 21971289 TI - Coupling corona discharge for ambient extractive ionization mass spectrometry. AB - Unlike the extractive electrospray ionization (EESI) technique described elsewhere, a corona discharge instead of electrospray ionization has been utilized to charge a neutral solvent spray under ambient conditions for the generation of highly charged microdroplets, which impact a neutral sample plume for the extractive ionization of the analytes in raw samples without any sample pretreatment. Using the positive ion mode, molecular radical cations were easily generated for the detection of non-polar compounds (e.g., benzene, cyclohexane, etc.), while protonated molecular ions of polar compounds (e.g., acetonitrile, acetic ether) were readily produced for the detection. By dispensing the matrix in a relatively large space, this method tolerates highly complex matrices. For a given sample such as lily fragrances, more compounds were detected by the method established here than the EESI technique. An acceptable relative standard deviation (RSD 8.9%, n = 11) was obtained for the direct measurement of explosives (10 ppb) in waste water samples. The experimental data demonstrate that this method could simultaneously detect both polar and non-polar analytes with high sensitivity, showing promising applications for the rapid detection of a wide variety of compounds present in complex matrices. PMID- 21971291 TI - In vitro genotoxicity testing strategy for nanomaterials and the adaptation of current OECD guidelines. AB - There is a pressing requirement to define a hazard identification and risk management strategy for nanomaterials due to the rapid growth in the nanotechnology industry and their promise of life-style revolutions through the development of wide-ranging nano-containing consumer products. Consequently, a battery of well defined and appropriate in vitro assays to assess a number of genotoxicity endpoints is required to minimise extensive and costly in vivo testing. However, the validity of the established protocols in current OECD recognised genotoxicity assays for nanomaterials is currently being questioned. In this report, we therefore consider the in vitro OECD genotoxicity test battery including the Ames, micronucleus and HPRT forward mutation assays, and their potential role in the safety assessment of nanomaterial induced DNA damage in vitro. PMID- 21971292 TI - Profenofos induced DNA damage in freshwater fish, Channa punctatus (Bloch) using alkaline single cell gel electrophoresis. AB - The aim of the present study was to evaluate the induced genotoxicity (DNA damage) due to organophosphate pesticide profenofos (PFF) in gill cells of freshwater fish Channa punctatus using single cell gel electrophoresis (SCGE)/Comet assay. The 96h LC(50) value of PFF (50% EC) was estimated for the fish species in a semistatic system and then three sub-lethal of LC(50) concentrations viz the sub-lethal 1, sub-lethal 2 and sub-lethal 3 concentrations were determined as 0.58ppb, 1.16ppb and 1.74ppb, respectively. The fish specimens were exposed to these concentrations of the pesticide and the gill tissue samplings were done on 24h, 48h, 72h and 96h post exposure for assessment of DNA damage in terms of percentage of DNA in comet tails. In general, a concentration dependent response was observed in the gill cells with induction of maximum DNA damage at the highest concentration of PFF. The results of the present investigation indicated that PFF could potentially induce genotoxic effect in fish, even in sub-lethal concentrations and SCGE as a sensitive and reliable tool for in vivo assessment of DNA damage caused by the genotoxic agents. PMID- 21971293 TI - Accuracy of prehospital diagnoses by emergency physicians: comparison with discharge diagnosis. AB - OBJECTIVE: A correct prehospital diagnosis of emergency patients is crucial as it determines initial treatment, admitting specialty, and subsequent treatment. We evaluated the diagnostic accuracy of emergency physicians. METHODS: All patients seen by six emergency physicians staffing the local emergency ambulance and rescue helicopter services during an 8-month period were studied. The ambulance and helicopter physicians had 3 and 4 years, respectively, training in anesthesia and intensive care medicine. The admission diagnoses were compared with the discharge diagnoses for agreement. Time of day of the emergency call, patients' age, and sex, living conditions, and presenting symptoms were evaluated as contributing factors. RESULTS: Three hundred and fifty-five ambulance and 241 helicopter deployment protocols were analyzed. The overall degree of agreement between initial and discharge diagnoses was 90.1% with no difference attributable to years of experience. The lowest agreement rate was seen in neurological disorders (81.5%), with a postictal state after an unobserved seizure often being diagnosed as a cerebrovascular accident. Inability to obtain a complete medical history (e.g. elderly patients, patients in nursing homes, neurological impairment) was associated with a lower agreement rate between initial and discharge diagnoses (P<0.05). CONCLUSION: Medical history, physical examination, ECG, and blood glucose enabled a correct diagnosis in most cases, but some were impossible to resolve without further technical and laboratory investigations. Only a few were definitively incorrect. A detailed medical history is essential. Neurological disorders can present with misleading symptoms and when the diagnosis is not clear it is better to assume the worst case. PMID- 21971294 TI - Optimization of 100 MUm alginate-poly-L-lysine-alginate capsules for intravitreous administration. AB - The field of cell microencapsulation is advancing rapidly. Particle size plays a critical role in terms of biocompatibility and limits decisively its applicability. Producing reduced size microcapsules involves broadening the possibilities to employ this technology in the treatment of many disorders. Nervous system diseases (NSD) represent a clear example of that. This work describes the feasibility of reducing the size of alginate-poly-L-lysine-alginate (APA) microcapsules up to 100 MUm in a highly monodisperse way using the novel Flow Focusing technique. C(2)C(12) myoblasts genetically engineered to express the triple reporter gene thymidine kinase-green fluorescent protein-luciferase (TGL) and secrete vascular endothelial growth factor soluble receptor 2 (VEGFR2, also known as KDR) were encapsulated for further characterization. Resulting new particles were assayed in vitro to explore whether their functionality might be affected due to the physicochemical changes arising from such dramatic size reduction. Not only were negative effects at this level not noticed in terms of cell viability, cell proliferation and KDR secretion, but once again the suitability of APA microcapsules was also reinforced against other microcapsule designs. Furthermore, the fully viable and functional biosystems were successfully administered in the intravitreous space of rats, where the activity of encapsulated cells was monitoring over 3 weeks. PMID- 21971295 TI - Poly(glycerol adipate)-fatty acid esters as versatile nanocarriers: From nanocubes over ellipsoids to nanospheres. AB - Poly(glycerol adipate) (PGA) is a biodegradable polymer with promising features for nanoparticulate drug carrier systems. By acylation of PGA with fatty acids, composite systems with amphiphilic properties can be obtained. Variation of the fatty acid (laurate, stearate and behenate) and their substitution degrees lead to a wide range of different polymer structures. This strongly influences the aggregation of the polymer and thus the nature of the resulting colloidal system. Based on the modification of the interfacial deposition method, various self stabilizing nanoparticles with defined sizes and narrow size distributions could be prepared. Non-spherical shapes (squares, pentagons) with an internal lamellar like structure were observed for low substituted PGA-stearates. Higher substitution degrees lead to ellipsoidal or spherical particles. The size, charge, fluidity and polarity of the nanoparticles have been studied comprehensively by PCS, AF4, zeta potential measurements, DSC, NMR, TEM and fluorescence spectroscopy. The chain lengths of the attached fatty acids as well as their substitution degree substantially influence the physicochemical properties of the bulk polymers and the nanoparticles. With their diverse particle shapes and internal structures as well as their different thermal behavior, aggregate states and polarities, the systems offer promising possibilities as delivery systems for lipophilic, amphiphilic and water soluble drugs. PMID- 21971297 TI - Physical activity, body mass index, and health-related quality of life in Canadian adults. AB - PURPOSE: Physical activity (PA) positively influences health-related quality of life (HRQL), whereas obesity is associated with significant HRQL impairments. Active-obese persons often have similar or lower risk of cardiovascular outcomes and mortality than inactive-healthy weight persons; however, the combined PA weight status effects on HRQL are unclear. The aim was to investigate the combined association of PA and body mass index (BMI) with HRQL in Canadian adults and older adults. METHODS: Cross-sectional data included 110,986 participants >= 18 yr from the 2005 Canadian Community Health Survey, representing an estimated 22,563,527 Canadians. HRQL indicators included: Self-Rated Health (SRH), Participation and Activity Limitation due to illness/injury (PAL), and Total Disability Days (physical + mental) during the past 14 d (TDD). Prevalence of adverse HRQL was estimated by BMI, PA, and combined BMI-PA categories. Adjusted logistic regression was used to assess the odds of adverse HRQL by BMI, PA, and BMI-PA. Analyses were stratified by sex and age (18-44, 45-64, >=65 yr). RESULTS: In both men and women of all ages, inactive individuals had greater likelihood of fair/poor SRH, and sometimes/often PAL, at all BMI levels; conversely, in active individuals, being underweight, overweight, or obese had little effect on SRH and PAL. Associations were weaker for TDD, where the greatest influence was in older adults from inactivity combined with underweight. Overweight showed less association to HRQL in males and older adults, whereas underweight showed stronger association in males and older adults. CONCLUSIONS: When examining BMI PA in combination, PA emerges as the more important correlate of HRQL, regardless of weight status. This reinforces the importance of PA to health outcomes over and above the benefits related to weight loss or maintenance. PMID- 21971296 TI - Capturing changes in gene expression dynamics by gene set differential coordination analysis. AB - Analyzing gene expression data at the gene set level greatly improves feature extraction and data interpretation. Currently most efforts in gene set analysis are focused on differential expression analysis--finding gene sets whose genes show first-order relationship with the clinical outcome. However the regulation of the biological system is complex, and much of the change in gene expression dynamics do not manifest in the form of differential expression. At the gene set level, capturing the change in expression dynamics is difficult due to the complexity and heterogeneity of the gene sets. Here we report a systematic approach to detect gene sets that show differential coordination patterns with the rest of the transcriptome, as well as pairs of gene sets that are differentially coordinated with each other. We demonstrate that the method can identify biologically relevant gene sets, many of which do not show first-order relationship with the clinical outcome. PMID- 21971298 TI - Does one size fit all? Building a framework for medical professionalism. AB - PURPOSE: Medical professionalism has gained global attention over the past decade, but there is a paucity of literature on the universal applicability of the dominant professionalism framework developed in the West. This study proposes an institutional approach to build a framework for medical professionalism that incorporates historical and sociocultural contexts. METHOD: From 2008 to 2009, the authors adopted nominal group technique (NGT) to determine professional competencies valued by 91 critical stakeholders of medical education (divided into 12 discipline-specific groups) at their institution and in their native society, Taiwan. An expert committee subsequently constructed a framework for professionalism which accounted for a literature review and their understanding of the institution's values and historical roots. To confirm that the framework encompassed the attributes nominated by NGT participants, the authors analyzed transcripts of NGT exercises to refine the final document. RESULTS: Each of 12 NGT groups raised 5 to 23 core competencies and determined the most important five competencies by summing participants' ratings of each item. The expert panel reached consensus on a framework that included eight competencies. The framework differs from the Western framework in the centrality of self-integrity, harmonizing personal and professional roles. Text analysis of the NGT transcripts demonstrated that the framework successfully incorporated top-ranked NGT results. CONCLUSIONS: This study challenges the universal applicability of the Western framework of medical professionalism and proposes a process to build a professionalism framework that reflects the cultural heritage and the values of local stakeholders. PMID- 21971299 TI - An interesting molecular-assembly of beta-cyclodextrin pipelines with embedded hydrophilic nickel maleonitriledithiolate. AB - A unique tubular molecular-assembly, constructed by beta-cyclodextrin and Na[Ni(mnt)(2)], was identified by X-ray crystallography. Inclusion complex Na[Ni(mnt)(2)]@beta-cyclodextrin (1) crystallized in space group P2(1)2(1)2 as hydrated head-to-head, tail-to-tail, and head-to-tail host pipelines with negatively charged [Ni(mnt)(2)](-) guests included, exhibiting a 3 : 1 (host : guest) stoichiometry. The hydrophilic transition-metal coordination compound (Na[Ni(mnt)(2)]) was embedded within a hydrophobic cyclodextrin cavity, which resulted in a beta-cyclodextrin trimer motif and one-third "empty" host packing model in the crystal. Induced circular dichroism (ICD) spectra of inclusion complex 1 was investigated, which indicated the same penetration pattern of the guests in host cavities in solution phase as that discovered in the crystal structure. In addition, PM3 quantum chemistry calculations strongly supported the co-conformational alignments of inclusion complex 1 that was identified in the crystal as well as in the solution. PMID- 21971300 TI - Simultaneous determination of purity and potency of amphotericin B by HPLC. AB - Currently, the quality-control strategy of amphotericin B in US Pharmacopoeia, British Pharmacopoeia, European Pharmacopoeia and Pharmacopoeia of the People's Republic of China all adopt the combination of purity measurement by HPLC and potency measurement by microbiological assay. In this study, we prepared pure amphotericin B and quantified the relationship between amphotericin B content and potency values using the mass-balance method and microbiological assay. The potency of amphotericin B with an absolute purity of 100% was determined to be 1048.63 U mg(-1). An HPLC method was then established to simultaneously determine the content and potency of amphotericin B, which unified the quality-control procedure for amphotericin B. A good linear relationship was observed between the peak area and the concentration, which could be expressed as y=113074x+4196.5, R(2)=0.9999. The lower limit of quantification was 0.4473 ng. The HPLC method is expected to become the routine quality-control method and replace the current laborious quality-control procedure in pharmacopoeias. PMID- 21971301 TI - Theoretical reconstruction and elementwise analysis of photoelectron spectra for imidazolium-based ionic liquids. AB - We have recently measured core level and valence band XPS, UPS, and MIES spectra of two room temperature ionic liquids composed of bis(trifluoromethylsulfonyl)imide anions ([Tf(2)N](-)) and either 1-ethyl-3 methyl-imidazolium ([EMIm](+)) or 1-octyl-3-methyl-imidazolium cations ([OMIm](+)). [T. Ikari, A. Keppler, M. Reinmoller, W. J. D. Beenken, S. Krischok, M. Marschewski, W. Maus-Friedrichs, O. Hofft and F. Endres, e-J. Surf. Sci. Nanotechnol., 2010, 8, 241.] In the present work we analyze these spectra by means of partial density of states (pDOS) as calculated from a single ion pair of the respective ionic liquid using density functional theory (DFT). Subsequently we reconstruct the XPS and UPS spectra by considering photoemission cross sections and analyze the MIES spectra by pDOS, which provides us decisive hints to the ionic liquid surface structure. PMID- 21971302 TI - Lower incidence of deletions in the survival of motor neuron gene and the neuronal apoptosis inhibitory protein gene in children with spinal muscular atrophy from Serbia. AB - Spinal muscular atrophy (SMA) is the second most frequent autosomal recessive disease characterized by degeneration of the anterior horn cells of the spinal cord, leading to muscular atrophy. SMA is classified into three types according to disease severity and age-onset: severe (type I), intermediate (type II) and mild (type III). Deletions in the survival motor neuron (SMN) gene, located in the chromosome region 5q11.2- 5q13.3, are major determinants of SMA phenotype. Extended deletions that include the neuronal apoptosis inhibitory protein (NAIP) gene may correlate with the severtity of SMA. SMN gene is present in two highly homologous copies, SMN1 and SMN2, but only deletions of the SMN1 gene (exons 7 and 8 or exon 7) are responsible for clinical manifestations of SMA. Here, we present the deletion profiling of SMN1 and NAIP genes in 89 children with SMA from Serbia: 52 patients with type I, 26 with type II, and 11 with type III. The homozygous deletion of the SMN1 gene was confirmed in 72 of 89 (81%) patients, being the most frequent in SMA type I (48/52): 68 patients (94.4%) with deletion of exons 7 and 8 and 4 patients (5.6%) with deletion of exon 7. The extended deletion including the NAIP gene was detected in 18 of 89 (20.2%) patients, mostly affected with type I. This study has revealed the lower incidence of deletions in the SMN1 and NAIP genes in families with SMA in Serbia and will provide important information for genetic counselling in these families. PMID- 21971303 TI - Superantigenic toxin genes coexist with specific staphylococcal cassette chromosome mec genes in methicillin-resistant Staphylococcus aureus. AB - Staphylococcus aureus is a leading cause of human disease in the hospital setting and the community. Superantigenic toxin-producing methicillin-resistant Staphylococcus aureus (MRSA) is currently important for nosocomial infections and food-borne diseases worldwide because of its global spreading and difficulty in therapy. Superantigenic toxins can bypass normal antigen presentation and have strong T cell mitogenic activity, leading to massive release of proinflammatory cytokines and contributing to the severity of S. aureus sepsis. In this study, a total of 131 MRSA isolates from patients in the University Hospital were searched for staphylococcal cassette chromosome mec (SCCmec) genes and the staphylococcal superantigenic toxin genes by multiplex polymerase chain reactions. The MRSA isolates were classified into SCCmec type II (74.8%), type I (13.0%), type IV (3.8%), type V (2.3%), and type I and type II (3.8%). MRSA isolates (102/131) also carried a number of superantigenic toxin genes including staphylococcal enterotoxin (se) and toxic shock syndrome toxin-1 (tst-1) genes. The most frequent superantigen gene profile (55/131, 42.0%) of the MRSA isolates includes staphylococcal enterotoxin C (sec), seg, sei, staphylococcal enterotoxin-like L (sell), selm, seln, selo, and tst-1. Furthermore, SCCmec type I or type II MRSA isolates more frequently harbor sec, seg, sei, sell, selm, seln, selo, and tst-1 genes, compared to other types of MRSA. These results indicate that the selected superantigenic toxin genes are linked to SCCmec type I and type II. The coexistence of these toxins and the SCCmec genes in S. aureus may contribute to the biological fitness and pathogenicity of MRSA. PMID- 21971304 TI - Association between renal dysfunction and the mixed plaque of coronary artery on computed tomographic angiography. AB - Coronary artery plaque is related to development of coronary artery disease (CAD), and chronic kidney disease is associated with CAD. However, the association of renal dysfunction (RD) with coronary artery plaque characteristics has not been fully elucidated. We evaluated the association between RD and coronary artery plaque characteristics in patients with suspected CAD, who underwent multislice computed tomographic angiography (CTA). A total of 918 patients were classified into 4 groups: group with no plaque (NP) (48.9%), group with calcified plaque (CP) (16.0%), group with noncalcified plaque (NCP) (22.4%), and group with mixed plaque (MP) (12.7%). NCP is considered as rupture-prone soft plaque, and CP as more stable lesion. The mean of estimated glomerular filtration rate (eGFR) was 82.5 +/- 15.4 mL/min/1.73 m(2), and the prevalence of RD (defined as eGFR < 60 mL/min/1.73 m(2)) was 6.3%. The prevalence of RD was 3.3% in the NP group, 10.2% in the CP group, 5.3% in the NCP group, and 14.5% in the MP group (P < 0.001 by ANOVA tests). The adjusted odds ratio for RD was 3.38 (95% confidence interval, 1.27-9.04) for the MP group, compared with the NP group. The presence of RD showed an independent association with the MP counts (r = 0.155, P < 0.001); however, there was no association between RD and other plaque characteristics. In conclusion, RD is associated with MP rather than CP or NCP, compared with NP, which may reflect one of the developmental processes of CAD in patients with RD. PMID- 21971305 TI - A vacuum pressure sensor based on ZnO nanobelt film. AB - A vacuum pressure sensor was fabricated by assembling ZnO nanobelt film on the interdigital electrodes, and the current-voltage characteristics were measured with an Agilent semiconductor parameter tester. Under different pressures of 1.0 * 10(3), 6.7 * 10(-3), 8.2 * 10(-4) and 9.5 * 10(-5) mbar, the currents are 8.71, 28.1, 46.1 and 89.6 nA, and the pressure sensitive resistances are 1150, 356, 217 and 112 MOmega, respectively. In the range of 10(-5)-10(3) mbar the smaller the pressure is, the higher the current is. The pressure sensitive resistance of the vacuum pressure sensor increases linearly with the logarithmic pressure, and the measurement range is at least one order of magnitude wider than that of the previous sensors. Under the final pressure, the vacuum pressure sensor has maximum sensitivity (9.29) and power consumption of 0.9 MUW. The sensitivity is larger than that of the previous sensor based on a ZnO single nanowire at that pressure, and the power consumption is much lower than that for the sensor based on a ZnO nanowire array. The pressure sensitive mechanism is reasonably explained by using oxygen chemisorption and energy band theory. PMID- 21971306 TI - When action is not enough: tool-use reveals tactile-dependent access to Body Schema. AB - Proper motor control of our own body implies a reliable representation of body parts. This information is supposed to be stored in the Body Schema (BS), a body representation that appears separate from a more perceptual body representation, the Body Image (BI). The dissociation between BS for action and BI for perception, originally based on neuropsychological evidence, has recently become the focus of behavioural studies in physiological conditions. By inducing the rubber hand illusion in healthy participants, Kammers et al. (2009) showed perceptual changes attributable to the BI to which the BS, as indexed via motor tasks, was immune. To more definitively support the existence of dissociable body representations in physiological conditions, here we tested for the opposite dissociation, namely, whether a tool-use paradigm would induce a functional update of the BS (via a motor localization task) without affecting the BI (via a perceptual localization task). Healthy subjects were required to localize three anatomical landmarks on their right arm, before and after using the same arm to control a tool. In addition to this classical task-dependency approach, we assessed whether preferential access to the BS could also depend upon the way positional information about forearm targets is provided, to subsequently execute the same task. To this aim, participants performed either verbally or tactually driven versions of the motor and perceptual localization tasks. Results showed that both the motor and perceptual tasks were sensitive to the update of the forearm representation, but only when the localization task (perceptual or motor) was driven by a tactile input. This pattern reveals that the motor output is not sufficient per se, but has to be coupled with tactually mediated information to guarantee access to the BS. These findings shade a new light on the action perception models of body representations and underlie how functional plasticity may be a useful tool to clarify their operational definition. PMID- 21971307 TI - About turn: how object orientation affects categorisation and mental rotation. AB - High-density ERPs evoked by rotated alphanumeric characters were examined to determine how neural processing is affected by stimulus orientation during letter/digit classifications and during mirror/normal discriminations. The former task typically produces response times that are unaffected by stimulus orientation while the latter is thought to require mental rotation. Sensitivity to orientation was first observed around 100-140 ms and this effect was attributed to differences in low-level features between vertical and oblique orientations. Subsequently, character misorientation amplified the N170, a neural marker of object classification, between 160 and 220 ms. Top-down processing is reflected in the ERPs beginning at 280-320 ms and this time range may reflect binding of ventral and dorsal stream information. In the case of mirror-normal discrimination these top-down processes can lead to mental rotation between 340 and 700 ms. Therefore, although neural processing reflects object orientation, these effects do not translate into increases in reaction-times or impaired accuracy for categorisation, and precede those that do in the mental-rotation task. PMID- 21971309 TI - Dydrogesterone exerts endothelial anti-inflammatory actions decreasing expression of leukocyte adhesion molecules. AB - Clinical observations and basic studies show that progesterone and progestins have a variable influence on endothelial function. Dydrogesterone (DG) is a widely used progestin, but its endothelial actions have not been thoroughly assessed. In this study, we investigated the effects of DG and its metabolite 20 alpha-dihydro-dydrogesterone (DHD), natural progesterone as well as medroxyprogesterone acetate, on the expression of leukocyte adhesion molecules in human endothelial cells using an in vitro experimental endothelial inflammation system. Our findings show that all progestins significantly suppress endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and inter-cellular adhesion molecule-1 (ICAM-1) induced by bacterial lypopolysaccharide (LPS). These inhibitory effects of DG and DHD require activation of progesterone receptor. DG and DHD decrease adhesion molecule expression associated with LPS administration by preventing nuclear translocation of the pro-inflammatory transcription factor nuclear factor-kappaB. In addition, DG and DHD do not alter the anti-inflammatory effects of 17beta-estradiol. In conclusion, DG and DHD decrease endothelial inflammatory responses induced by LPS, via reduced expression of the pro atherogenic adhesion molecules VCAM-1 and ICAM-1. These actions may be relevant for the vascular effects of DG. PMID- 21971308 TI - The other face of the other-race effect: an fMRI investigation of the other-race face categorization advantage. AB - The present study was the first to use the functional magnetic resonance imaging (fMRI) methodology to investigate the neural correlates of race categorization of own- and other-race faces. We found that Chinese participants categorized the race of Caucasian faces more accurately and faster than that of Chinese faces, replicating the robust effect of the other-race categorization advantage. Regions of interest (ROI) analyses revealed greater neural activations when participants were categorizing own-race faces than other-race faces in the bilateral ventral occipito-temporal cortex (VOT) such as the fusiform face areas (FFAs) and the occipital face areas (OFAs). Within the left FFA, there was also a significant negative correlation between the behavioral difference of own- and other-race face categorization accuracy and the activation difference between categorizing own- and other-race faces. Whole brain analyses showed that categorizing own-race faces induced greater activations in the right medial frontal cortex (MFC) and right inferior frontal gyrus (IFG) than categorizing other-race faces. Psychophysiological interaction (PPI) analyses revealed that the frontal cortical regions interacted more strongly with the posterior VOT during the categorization of own-race faces than that of other-race faces. Overall, our findings suggest that relative to the categorization of other-race faces, more cortical resources are engaged during the categorization of own-race faces with which we have a higher level of processing expertise. This increased involvement of cortical neural sources perhaps serves to provide more in-depth processing of own-race faces (such as individuation), which in turn paradoxically results in the behavioral other-race categorization advantage. PMID- 21971310 TI - Proteomic strategy for the identification of critical actors in reorganization of the post-meiotic male genome. AB - After meiosis, during the final stages of spermatogenesis, the haploid male genome undergoes major structural changes, resulting in a shift from a nucleosome based genome organization to the sperm-specific, highly compacted nucleoprotamine structure. Recent data support the idea that region-specific programming of the haploid male genome is of high importance for the post-fertilization events and for successful embryo development. Although these events constitute a unique and essential step in reproduction, the mechanisms by which they occur have remained completely obscure and the factors involved have mostly remained uncharacterized. Here, we sought a strategy to significantly increase our understanding of proteins controlling the haploid male genome reprogramming, based on the identification of proteins in two specific pools: those with the potential to bind nucleic acids (basic proteins) and proteins capable of binding basic proteins (acidic proteins). For the identification of acidic proteins, we developed an approach involving a transition-protein (TP)-based chromatography, which has the advantage of retaining not only acidic proteins due to the charge interactions, but also potential TP-interacting factors. A second strategy, based on an in-depth bioinformatic analysis of the identified proteins, was then applied to pinpoint within the lists obtained, male germ cells expressed factors relevant to the post-meiotic genome organization. This approach reveals a functional network of DNA-packaging proteins and their putative chaperones and sheds a new light on the way the critical transitions in genome organizations could take place. This work also points to a new area of research in male infertility and sperm quality assessments. PMID- 21971312 TI - MBD 4--a potential substrate for protein kinase X. PMID- 21971311 TI - Frequency of hepatitis B virus DNA in anti-HBc positive, HBsAg negative blood donors in Rasht, northern Iran. AB - BACKGROUND: One of the important factors in the ensuing safety of blood transfusion is to use a sensitive screening assay for detection of blood-born infective agents such as HBV which transmits through transfusion. To improve the detection rate of HBV infection in blood donors, a cross-sectional study was conducted in Rasht, which is the largest city in the north of Iran to explore the possibility of using anti-HBc as a screening test. STUDY DESIGN AND METHODS: A total of 2041 blood samples negative for HBsAg, Anti-HCV, Anti-HIV I, II and RPR were tested to detect anti-HBc and then the positive anti-HBc samples were further checked for the presence of HBV DNA. RESULTS: The prevalence of anti-HBc positive samples was 3.8% and HBV DNA was detected in only one sample. CONCLUSIONS: This study showed that anti-HBc positive blood donors may be a source of HBV transmission and further study for evaluation of HBV DNA in anti HBc positive blood units is needed. PMID- 21971313 TI - Testicular cancer: low gestational age increases risk. PMID- 21971314 TI - Pediatrics: steroids can reduce renal scarring. PMID- 21971315 TI - From urgency to frequency: facts and controversies of TRPs in the lower urinary tract. AB - The members of transient receptor potential (TRP) superfamily of cationic ion channels represent universal sensors, which convert multiple exogenous and endogenous chemical and physical stimuli into electrical and functional cellular responses. TRPs are widely distributed in many different tissues, and expression of numerous TRP types has been reported in lower urinary tract (LUT) tissues, neuronal fibers innervating the bladder and urethra, and epithelial and muscular layers of the bladder and urethral walls, where they are mainly involved in nociception and mechanosensory transduction. As such, they represent attractive targets for treating LUT disorders. Although information on the functional significance of many of the TRP proteins in the LUT remains very limited, compelling evidence has accumulated for a pivotal role of TRPV1, TRPV2, TRPV4, TRPM8, and TRPA1 in normal and pathological LUT function, mainly as sensors of stretch and chemical irritation. Further studies into these and other TRPs in the LUT will facilitate the development of improved therapeutic strategies to target these channels in LUT disorders. PMID- 21971316 TI - Reactive oxygen species-mediated therapeutic control of bladder cancer. AB - Urinary bladder cancer is the fifth most common cancer in the US and the most costly cancer to manage because it requires life-long surveillance to monitor for recurrence and advanced progression. Urothelial carcinomas account for more than 90% of urinary bladder cancer cases. Transurethral resection and intravesical chemotherapy or immunotherapy are effective short-term treatments of urothelial carcinoma, but long-term management has not yet been optimized. Recent therapeutic strategies emphasize the targeted interference with aberrantly regulated signaling modulators that result from genomic alterations. However, targeted therapeutic agents might not distinguish cancer cells from their normal counterparts, resulting in undesirable adverse effects. Thus, a new approach for the treatment of urothelial carcinoma has been suggested that differentially augments cancer-associated events, leading to selective death of cancer cells but not normal cells. Many aberrantly-regulated signaling modulators are associated with the elevation of reactive oxygen species (ROS), and an increasing number of studies report agents with the ability to induce ROS in cancer cells. Accordingly, therapeutic augmentation of ROS to a lethal level in cancer cells only would induce selective death of tumor cells but not normal cells, leading to a highly effective chemotherapy strategy for urothelial carcinoma. PMID- 21971317 TI - Kidney cancer: long-term use of nonaspirin NSAIDs increases RCC risk. PMID- 21971319 TI - Milrinone, a phosphodiesterase III inhibitor, prevents reduction of jugular bulb saturation during rewarming from hypothermic cardiopulmonary bypass. AB - INTRODUCTION: Inadequate cerebral oxygen balance during cardiopulmonary bypass may cause neuropsychological dysfunction. Milrinone, a phosphodiesterase III inhibitor, augments cerebral blood flow by direct vasodilatation. We conducted a prospective, randomized study in patients undergoing cardiac surgery with cardiopulmonary bypass to clarify the clinical efficacy of milrinone in the imbalance of cerebral oxygen supply and demand during the rewarming period of cardiopulmonary bypass. METHODS: This is a prospective, randomized and placebo controlled study. After anesthesia, a 5.5 F fiberoptic oximeter catheter was inserted into the right jugular bulb retrogradely for monitoring the jugular venous oxyhemoglobin saturation (SjO(2)). Patients were randomly assigned to two groups, one receiving a continuous infusion of milrinone, 0.5 ug/kg/min during hypothermic cardiopulmonary bypass, and the other receiving saline as control. RESULTS: Milrinone significantly prevented the reduction of the jugular venous oxyhemoglobin saturation at 10 minutes from the start of rewarming compared with the control group, but did not do so from 10 to 20 minutes after rewarming. CONCLUSION: Milrinone suppresses the reduction of SjO(2) and improves the balance of cerebral oxygen supply and demand during the early rewarming period of hypothermic cardiopulmonary bypass. PMID- 21971320 TI - Prone and ECMO - a contradiction per se? AB - Acute respiratory distress syndrome (ARDS) still represents a serious problem in clinical routine and is associated with a high mortality. Several concepts are known for special treatment, but, in some instances, the application of an extracorporeal membrane oxygenation (ECMO) is necessary for both the improvement of oxygenation and the elimination of carbon dioxide (CO(2)). One basic aspect in lung protective ventilation in this context is alveolar recruitment, which can be achieved by different approaches, such as "the open lung concept", according to Lachmann, or by additional kinetic therapy. The most exposed feature of this entity is 'prone', which may be quite challenging in patients requiring extracorporeal support or organ replacement therapy under ongoing critical illness. We report two outstanding cases of prone under conditions of a veno venous ECMO therapy which improved significantly under this position. Furthermore, we reflect critically possible risk factors and adverse events of such procedures and afford a current view from the literature. PMID- 21971318 TI - Prolactin regulation of the prostate gland: a female player in a male game. AB - Prolactin is best known for its actions on the mammary gland. However, circulating prolactin is also detected in males and its receptor (PRLR) is expressed in the prostate, suggesting that the prostate is a target of prolactin. Germline knockout of prolactin or its receptor has failed to reveal a key role for prolactin signaling in mouse prostate physiology. However, several studies involving rodent models and human prostate cell lines and specimens have supported the contribution of the canonical PRLR-Jak2-Stat5a/b pathway to prostate cancer tumorigenesis and progression. Increased expression of prolactin in the prostate itself (rather than changes in circulating prolactin levels) and crosstalk with androgen receptor (AR) signaling are potential mechanisms for increased Stat5a/b signaling in prostate cancer. In the mouse prostate, prolactin overexpression results in disorganized expansion of the basal/stem cell compartment, which has been proposed to house putative prostate tumor-initiating cells. These findings provide new insight into the molecular and cellular targets by which locally produced prolactin could contribute to prostate cancer initiation and progression. A number of pharmacological inhibitors targeting various levels of the PRLR-Jak2-Stat5a/b pathway have been developed and are entering clinical trials for advanced prostate cancer. PMID- 21971321 TI - Digital image analysis in pathology: benefits and obligation. AB - Pathology has recently entered the era of personalized medicine. This brings new expectations for the accuracy and precision of tissue-based diagnosis, in particular, when quantification of histologic features and biomarker expression is required. While for many years traditional pathologic diagnosis has been regarded as ground truth, this concept is no longer sufficient in contemporary tissue-based biomarker research and clinical use. Another major change in pathology is brought by the advancement of virtual microscopy technology enabling digitization of microscopy slides and presenting new opportunities for digital image analysis. Computerized vision provides an immediate benefit of increased capacity (automation) and precision (reproducibility), but not necessarily the accuracy of the analysis. To achieve the benefit of accuracy, pathologists will have to assume an obligation of validation and quality assurance of the image analysis algorithms. Reference values are needed to measure and control the accuracy. Although pathologists' consensus values are commonly used to validate these tools, we argue that the ground truth can be best achieved by stereology methods, estimating the same variable as an algorithm is intended to do. Proper adoption of the new technology will require a new quantitative mentality in pathology. In order to see a complete and sharp picture of a disease, pathologists will need to learn to use both their analogue and digital eyes. PMID- 21971327 TI - ACMA (9-amino-6-chloro-2-methoxy acridine) forms three complexes in the presence of DNA. AB - The interaction of ACMA (9-amino-6-chloro-2-methoxy acridine) (D) with DNA (P) has been studied by absorbance, fluorescence, circular dichroism, spectrophotometry, viscometry and unwinding electrophoresis. A T-jump kinetic study has also been undertaken. The experimental data show that, totally unlike other drugs, ACMA is able to form with DNA three complexes (PD(I), PD(II), PD(III)) that differ from each other by the characteristics and extent of the binding process. The main features of PD(I) fulfil the classical intercalation pattern and the formation/dissociation kinetics have been elucidated by T-jump techniques. PD(II) and PD(III) are also intercalated species but, in addition to the dye units lodged between base pairs, they also bear dye molecules externally bound, more in PD(III) relative to PD(II). A reaction mechanism is put forward here. Comparison between absorbance, fluorescence and kinetic experiments has enabled us to determine the binding constants of the three complexes, namely (6.5 +/- 1.1) * 10(4) M(-1) (PD(I)), (5.5 +/- 1.5) * 10(4) M(-1) (PD(II)) and (5.7 +/- 0.03) * 10(4) M(-1) (PD(III)). The Comet assay reveals that the ACMA binding to DNA brings about genotoxic properties. The mutagenic potential studied by the Ames test reveals that ACMA can produce frameshift and transversion/transition mutations. ACMA also is able to produce base-pair substitution in the presence of S9 mix. Moreover, the MTT assays have revealed cytotoxicity. The biological effects observed have been rationalized in light of these features. PMID- 21971328 TI - Specific immunotherapy, one century later. PMID- 21971329 TI - Risk factors for systemic reactions to allergen immunotherapy. AB - PURPOSE OF REVIEW: To update safety information regarding allergen-specific immunotherapy (ASIT) in clinical practice and highlight the risk factors associated with the adverse reactions, product and each dose. RECENT FINDINGS: Efforts in recent years have focused on increasing our understanding of the efficacy and safety of ASIT, especially the sublingual variety (SLIT), in multicenter studies. Moreover, new Clinical Practice Guidelines (CPGs) and an international consensus concerning ASIT have been published recently. Although no deaths as a result of subcutaneous immunotherapy or SLIT have been reported in the last 2 years, systemic reactions mainly arising from administration errors still appear. Recent studies support the safety of new forms of specific immunotherapy. SUMMARY: An understanding of the risk factors for each patient, product and dose, and the implementation of CPGs are the main factors that could improve the safety of ASIT. The standardization of all procedures for prescribing and administering ASIT, and the systematic collection of standardized safety data in a multicenter database (postmarketing surveillance), may be required to generate new information on the safety of ASIT. PMID- 21971330 TI - Choices in IgG replacement therapy for primary immune deficiency diseases: subcutaneous IgG vs. intravenous IgG and selecting an optimal dose. AB - PURPOSE OF REVIEW: Subcutaneous IgG (SCIG) is becoming more popular, but there is still uncertainty about efficacy and optimal dosing. This review discusses recent pharmacokinetic studies and applications of SCIG therapy, and its efficacy in the context of emerging understanding of the relationship between dosing and efficacy of both intravenous IgG (IVIG) and SCIG replacement therapy for primary immunodeficiency diseases. RECENT FINDINGS: Three preparations of IgG have been licensed in the US in the past year. Their bioavailabilities are 65-70% of that of IVIG. Pooled analyses show that the efficacy of SCIG in preventing infections is proportional to the steady-state levels achieved, and similar to that of IVIG. Pharmacokinetic studies allow estimation of doses that will yield desired serum levels with both IVIG and SCIG, and when switching from one route to another. SUMMARY: Pooled analyses show that at equivalent total doses, weekly SCIG results in steady-state levels 10-20% higher than troughs on monthly IVIG. For most patients, the choice between routes should be based on individual preference, and the regimen should be individualized to achieve the desired outcomes. PMID- 21971331 TI - The expanding spectrum of hemophagocytic lymphohistiocytosis. AB - PURPOSE OF REVIEW: Hemophagocytic lymphohistiocytosis (HLH) is more widely recognized by clinicians. No longer viewed as a disorder of young children, adult patients are now being identified and treated. In this review, I summarize clinical features of patients with recently identified genetic causes, discuss a new paradigm for understanding the clinical evolution of HLH, and update current results with hematopoietic cell transplantation. RECENT FINDINGS: The list of genetic defects underlying HLH continues to grow. Among the autosomal recessive defects underlying HLH, we add STX11 (Syntaxin 11) - a snare protein, and MUNC18 2 (also known as STXBP2 - Syntaxin-binding protein). These two proteins now join MUNC 13-4 as components of the degranulation machinery in cytotoxic lymphocytes, responsible for the delivery of Perforin and Granzyme B to selectively kill target cells. The mechanism of action in the newest X-linked disorder associated with HLH, XIAP deficiency (also termed XLP 2), is currently unknown. Treatment of HLH has also improved in recent years, at least in experienced centers where a significant number of patients are seen. Clinicians who are familiar with the dynamic evolution of the disease are learning how to modify treatment when initial or continuation therapy fails to achieve a stable clinical status, preferably clinical remission. Use of reduced intensity conditioning protocols pretransplant has resulted in superior short-term and long-term survival rates of greater than 85%. SUMMARY: Substantial progress continues to be made in exploring the complex cause and pathophysiology of HLH. Hand in hand, a greater recognition of the condition has led to improved treatments. PMID- 21971332 TI - Gene therapy for the Wiskott-Aldrich syndrome. AB - BACKGROUND: Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency (PID) characterized by micro-thrombocytopenia, recurrent infections, eczema, which is associated with a high incidence of auto-immunity and lymphoreticular malignancy. One of the first diseases to be successfully treated by allogeneic hematopoietic stem cell transplantation, WAS is currently the subject of several phase I/II gene therapy trials for patients without HLA compatible donors. PURPOSE OF REVIEW: This article reviews the preclinical and clinical data leading to the development of gene therapy of WAS with lentiviral vectors. RECENT FINDINGS: A recent clinical trial using a conventional gammaretroviral vector has demonstrated the proof of principle of gene therapy in WAS, but has also highlighted a common limitation of the technology. Encouraging preclinical efficacy and safety results using refined lentiviral vectors, and the development of robust clinical-grade manufacturing processes have supported the initiation of several phase I/II new studies. SUMMARY: WAS is amenable to hematopoietic stem cell gene therapy. New trials using lentiviral vectors are expected to improve efficacy and safety profiles. Beyond proof of principle, ongoing international efforts to coordinate trials of gene therapy for the WAS may also provide a model for the expedited development of new treatments for other rare diseases. PMID- 21971333 TI - T-cell receptor excision circles in primary immunodeficiencies and other T-cell immune disorders. AB - PURPOSE OF REVIEW: The thymus gland provides an environment for the production of rearranged diversified populations of T-cell receptors (TCRs) expressed on peripheral T cells. These receptors respond to nonself-antigens and are tolerant to self-antigens. During TCR rearrangement processes, unused excised DNA fragments create byproducts termed TCR excision circles (TRECs). Although these byproducts have no function, their detection in the peripheral blood stream is a clear indication that a rearrangement process has occurred. Their enumeration in the latest circle created during TCR delta deletion and the final TCR alpha rearrangement can determine thymus output. RECENT FINDINGS: Since the first description of its monitoring changes in the frequency of recent thymic emigrants with age and in human immunodeficiency virus (HIV)1 infection, TREC assessments have been used in many clinical settings in which T-cell immunity is involved, including diagnosing, understanding and monitoring T-cell immunodeficiencies, HIV infection, aging, autoimmune diseases and immune reconstitution after bone marrow transplantation. SUMMARY: Confounding factors, such as cell division, cell death, longevity of the naive T cells, and intracellular degradation, are known to affect TREC levels, yet measurement of TREC content is still considered the most reliable tool for tracking recent thymic emigrants. Its recent implantation for neonatal screening to diagnose severe combined immunodeficiency by using dry blood spots from Guthrie papers makes TREC the most accurate noninvasive tool to detect T-cell immune disorders. Together with determination of the TCR repertoire, TREC contents can give a clear insight into peripheral T-cell homeostasis. PMID- 21971334 TI - Allergen immunotherapy: a history of the first 100 years. AB - PURPOSE OF REVIEW: To provide a historical perspective on the development of allergen immunotherapy and to describe the progress that has been made in both the clinical application and the scientific understanding of this therapeutic technique in the 100 years since its inception. RECENT FINDINGS: Although allergen immunotherapy has been part of allergy practice for a century, it is only in relatively recent years that the cellular and molecular mechanisms which underlie its clinical efficacy have been elucidated. Most recent studies implicate the T-regulatory cell response as central to the development of a tolerogenic state in response to allergen immunotherapy, with both IL-10 and TGF beta playing crucial roles in the development of this cell subset. The clinical application of immunotherapy continues to advance, with promising contemporary studies noting improved safety and efficacy with pretreatment using omalizumab prior to an immunotherapy program as well as the potential for innate immune system modulation with allergen conjugates which can stimulate pattern recognition receptors such as the toll-like receptors. SUMMARY: After 100 years of clinical application, allergen immunotherapy remains the only treatment modality with the potential for long-term immunologic amelioration of atopic diseases. Future treatment advances in allergen immunotherapy will likely harness the increasing power of molecular and genomic medicine to achieve greater allergen specificity, while improving overall efficacy and minimizing the potential for systemic reactions. PMID- 21971335 TI - Anti-interleukin-5 antibody therapy in asthma and allergies. AB - PURPOSE OF REVIEW: Interleukin 5 (IL-5) has been shown to play an instrumental role in eosinophilic inflammation in allergic diseases. The purpose of this review is to explore clinical trials of anti-IL-5 antibody therapy that have been conducted in patients with asthma, hypereosinophilic syndromes, eosinophilic esophagitis, atopic dermatitis, Churg-Strauss syndrome, and nasal polyposis. RECENT FINDINGS: Recent trials of anti-IL-5 in patients with severe asthma refractory to existing therapies and prominent sputum eosinophilia experienced significant reductions in asthma exacerbations. Studies in patients with hypereosinopihilic syndromes have shown that IL-5 antagonism allows significant reductions in systemic corticosteroid doses while maintaining or improving blood eosinophil counts and symptoms. In children and adults with eosinophilic esophagitis, anti-IL-5 treatment reduced eosinophil numbers in esophageal tissue; it is uncertain whether these findings are predictive of clinical improvement. Clinical studies of individuals with atopic dermatitis do not support efficacy of anti-IL-5 in either reducing allergen patch test intensity or symptoms of chronic dermatitis. In small trials in both Churg Strauss syndrome and nasal polyposis, anti-IL-5 shows promise but larger numbers of patients with these conditions will need to be studied. SUMMARY: Anti-IL-5 is efficacious in treating patients with severe asthma and sputum eosinophilia and hypereosinophilic syndromes. Larger controlled trials with appropriate endpoints will be necessary to assess the role of anti-IL-5 in other eosinophilic disorders. PMID- 21971336 TI - Primary immunodeficiency: a never ending story. PMID- 21971337 TI - Nonviral delivery of genetic medicine for therapeutic angiogenesis. AB - Genetic medicines that induce angiogenesis represent a promising strategy for the treatment of ischemic diseases. Many types of nonviral delivery systems have been tested as therapeutic angiogenesis agents. However, their delivery efficiency, and consequently therapeutic efficacy, remains to be further improved, as few of these technologies are being used in clinical applications. This article reviews the diverse nonviral gene delivery approaches that have been applied to the field of therapeutic angiogenesis, including plasmids, cationic polymers/lipids, scaffolds, and stem cells. This article also reviews clinical trials employing nonviral gene therapy and discusses the limitations of current technologies. Finally, this article proposes a future strategy to efficiently develop delivery vehicles that might be feasible for clinically relevant nonviral gene therapy, such as high-throughput screening of combinatorial libraries of biomaterials. PMID- 21971338 TI - Detection and analysis of airborne particles of biological origin: present and future. AB - Detection and identification of bioaerosols in the environment presents a unique analytical challenge. The complexity and variation of the analyte, coupled with the disparity of the end users required information has led to the establishment of a huge number of approaches for detection. In general these approaches may be divided into two elements; sampling, describing the physical process used to capture the bioaerosols and analysis, the method by which the bioaerosols are counted and identified. There are a large number of methodologies for both these elements, mainly due to the diversity of applications, and a very unhealthy absence of consensus on standardisation for these approaches. This is an analytical application where 'one size does not fit all'; nevertheless standardisation is still essential. The focus of this review will clarify the challenge, by discussing the many different bioaerosols to be measured and the required user output, also to give a critique of the various analytical approaches that exist to date, including other promising methodologies that could be applied. PMID- 21971339 TI - Protein energy malnutrition predicts complications in liver cirrhosis. AB - BACKGROUND: Protein energy malnutrition frequently occurs in liver cirrhosis. Hand-grip strength according to Jamar is most reliable to predict protein energy malnutrition. We aimed to determine whether protein energy malnutrition affects complication risk. METHODS: In 84 cirrhotics, baseline nutritional state was determined and subsequent complications prospectively assessed. Influence of potentially relevant factors including malnutrition (by Jamar hand-grip strength) on complication rates were evaluated with univariate analysis. Effect of malnutrition was subsequently evaluated by multivariate logistic regression with adjustment for possible confounders. RESULTS: Underlying causes of cirrhosis were viral hepatitis in 31%, alcohol in 26%, and other in 43%. Baseline Child-Pugh (CP) class was A, B, or C in 58, 35, and 7%, respectively. Energy and protein intake decreased significantly with increasing CP class, with shift from proteins to carbohydrates. At baseline, according to Jamar hand-grip strength, malnutrition occurred in 67% (n=56). Malnutrition was associated with older age and higher CP class (CP class A 57%, B 79%, C 100%) but not with underlying disease or comorbidity. Complications occurred in 18 and 48% in well-nourished and malnourished patients, respectively, (P=0.007) during 13 +/- 6 months follow up. In multivariate analysis, malnutrition was an independent predictor of complications, after correcting for comorbidity, age, and CP score (adjusted odds ratio 4.230; 95% confidence interval 1.090-16.422; P=0.037). In univariate analysis, mortality (4 vs. 18%; P=0.1) tended to be worse in malnourished patients, but this trend was lost in multivariate analysis. CONCLUSION: Malnutrition is an independent predictor of complications in cirrhosis. PMID- 21971340 TI - Meperidine: a safe analgezic option for percutaneous liver biopsy. PMID- 21971341 TI - Re: Prophylactic analgesia before percutaneous liver biopsy: a clinical comparative study. PMID- 21971342 TI - Additive effect of folic acid deficiency on pegylated interferon's bone marrow toxicity. PMID- 21971343 TI - Acoustic radiation force impulse elastography is useful to exclude nonliver related ascites. PMID- 21971344 TI - The significance of ileo-colonic lymphoid nodular hyperplasia in children with autistic spectrum disorder: expression of concern. PMID- 21971346 TI - Long-term outcome of ablative therapy of post-operative atrial tachyarrhythmias in patients with tetralogy of Fallot: a European multi-centre study. AB - AIM: Post-operative atrial tachyarrhythmias (AT) in patients with tetralogy of Fallot (ToF) are associated with congestive heart failure, stroke, and cardiac death. Effective treatment is therefore essential. The aim of the study is to evaluate long-term outcome of ablative therapy of AT in ToF patients and to study characteristics of AT recurrences. METHODS AND RESULTS: Tetralogy of Fallot patients (N = 38, age 43 +/- 12 years) referred for ablation of post-operative AT, appearing 26 +/- 10 years after complete repair, were studied. Electro anatomical/entrainment mapping was performed prior to ablation. Successful ablation was defined as (i) achievement of bi-directional conduction block for isthmus-dependent atrial flutter (IDAF), (ii) termination during ablation for intra-atrial reentrant tachycardia (IART) and focal atrial tachycardia (FAT). Fifty-two AT were ablated, including 37 IDAF [cycle length (CL) 294 +/- 70 ms], 11 IART (CL 295 +/- 46 ms), and 4 FAT (CL 371 +/- 93 ms). Ablation was successful in 98%. Fifty-one of 52 AT involved the cavo-tricuspid isthmus and/or the area between scar tissue related to prior atriotomy incisions and the inferior caval vein. Multiple AT developed in 11 patients, with different mechanisms in 9. After 45 +/- 24 months, 32 patients were in sinus rhythm; 5 used anti-arrhythmic drugs. CONCLUSION: Ablative therapy of AT in ToF patients is an effective curative treatment modality with a high procedural success rate. Sinus rhythm during long term follow-up was obtained in the majority of patients. Fifty-one of 52 AT originated from sites related to surgical incisions created at complete repair, suggesting that extending the atriotomy incision towards the inferior caval vein during cardiac surgery combined with surgical ablation of the cavo-tricuspid isthmus will be effective in preventing development of AT. PMID- 21971347 TI - A potential copper-regulatory role for cytosolic expression of the DNA repair protein XRCC5. AB - Copper (Cu) has a critical role in the generation of oxidative stress during neurodegeneration and cancer. Reactive oxygen species generated through abnormal elevation or deficiency of Cu can lead to lipid, protein, and DNA damage. Oxidation of DNA can induce strand breaks and is associated with altered cell fate including transformation or death. DNA repair is mediated through the action of the multimeric DNA-PK repair complex. The components of this complex are the Ku autoantigens, XRCC5 and XRCC6 (Ku80 and Ku70, respectively). How this repair complex responds to perturbed Cu homeostasis and Cu-mediated oxidative stress has not been investigated. We previously reported that XRCC5 expression is altered in response to cellular Cu levels, with low Cu inhibiting XRCC5 expression and high Cu levels enhancing expression. In this study we further investigated the interaction between XRCC5 and Cu. We report that cytosolic XRCC5 is increased in response to Cu, but not zinc, iron, or nickel, and the level of cytosolic XRCC5 correlates with protection against oxidative damage to DNA. These observations were made in both HeLa cells and fibroblasts. Cytosolic XRCC5 interacted with the Cu chaperone and detoxification protein human Atox1 homologue (HAH), and down regulation of XRCC5 expression using siRNA led to enhanced HAH expression when cells were exposed to Cu. XRCC5 could also be purified from cytosolic extracts using a Cu-loaded column. These findings provide further evidence that cytosolic XRCC5 has a key role in protection against DNA oxidation from Cu, through either direct sequestration or signaling through other Cu-detoxification molecules. Our findings have important implications for the development of therapeutic treatments targeting Cu in neurodegeneration and/or cancer. PMID- 21971348 TI - Mitochondrial oxidative stress and respiratory chain dysfunction account for liver toxicity during amiodarone but not dronedarone administration. AB - The role played by oxidative stress in amiodarone-induced mitochondrial toxicity is debated. Dronedarone shows pharmacological properties similar to those of amiodarone but several differences in terms of toxicity. In this study, we analyzed the effects of the two drugs on liver mitochondrial function by administering an equivalent human dose to a rat model. Amiodarone increased mitochondrial H(2)O(2) synthesis, which in turn induced cardiolipin peroxidation. Moreover, amiodarone inhibited Complex I activity and uncoupled oxidative phosphorylation, leading to a reduction in the hepatic ATP content. We also observed a modification of membrane phospholipid composition after amiodarone administration. N-acetylcysteine completely prevented such effects. Although dronedarone shares with amiodarone the capacity to induce uncoupling of oxidative phosphorylation, it did not show any of the oxidative effects and did not impair mitochondrial bioenergetics. Our data provide important insights into the mechanism of mitochondrial toxicity induced by amiodarone. These results may greatly influence the clinical application and toxicity management of these two antiarrhythmic drugs. PMID- 21971349 TI - Neuroglial metabolic compartmentation underlying leptin deficiency in the obese ob/ob mice as detected by magnetic resonance imaging and spectroscopy methods. AB - Manganese-Enhanced Magnetic Resonance Imaging (MEMRI), (1)H and (13)C High Resolution-Magic Angle Spinning (HR-MAS) Spectroscopy, and genomic approaches were used to compare cerebral activation and neuronal and glial oxidative metabolism in ad libitum fed C57BL6/J leptin-deficient, genetically obese ob/ob mice. T(1)-weighted Magnetic Resonance Images across the hypothalamic Arcuate and the Ventromedial nuclei were acquired kinetically after manganese infusion. Neuroglial compartmentation was investigated in hypothalamic biopsies after intraperitoneal injections of [1-(13)C]glucose or [2-(13)C]acetate. Total RNA was extracted to determine the effects of leptin deficiency in the expression of representative genes coding for regulatory enzymes of hypothalamic energy pathways and glutamatergic neurotransmission. Manganese-Enhanced Magnetic Resonance Imaging revealed enhanced cerebral activation in the hypothalamic Arcuate and Ventromedial nuclei of the ob/ob mice. (13)C HR-MAS analysis showed increased (13)C accumulation in the hypothalamic glutamate and glutamine carbons of ob/ob mice after the administration of [1-(13)C]glucose, a primarily neuronal substrate. Hypothalamic expression of the genes coding for glucokinase, phosphofructokinase, pyruvate dehydrogenase, and glutamine synthase was not significantly altered while pyruvate kinase expression was slightly upregulated. In conclusion, leptin deficiency associated with obesity led to increased cerebral activation in the hypothalamic Arcuate and Ventromedial nuclei, concomitant with significant increases in neuronal oxidative metabolism and glutamatergic neurotransmission. PMID- 21971351 TI - New clues and new questions regarding leptin and brain metabolism. PMID- 21971350 TI - Lack of neuroprotection of inhibitory peptides targeting Jun/JNK after transient focal cerebral ischemia in spontaneously hypertensive rats. AB - In this study, we have assessed the ability of two TAT-fused peptides PYC36D-TAT and JNKI-1D-TAT (JNKI-1 or XG-102), which respectively inhibit jun proto-oncogene (c-Jun) and c-Jun N-terminal kinase (JNK) activation, to reduce infarct volume and improve functional outcome (adhesive tape removal) after transient focal cerebral ischemia in Spontaneously Hypertensive (SH) rats. PYC36D-TAT and JNKI-1D TAT peptide batches used for experiments were tested in vitro and protected cortical neurons against glutamate excitotoxicity. Rats were treated intravenously with three different doses of PYC36D-TAT (7.7, 76, or 255 nmol/kg), JNKI-1D-TAT (255 nmol/kg), D-TAT peptide (255 nmol/kg), or saline (vehicle control), 10 minutes after reperfusion after 90 minutes of middle cerebral artery occlusion (MCAO). Contrary to other stroke models, no treatment significantly reduced infarct volume or improved functional score measurements compared with vehicle-treated animals when assessed 48 hours after MCAO. Additionally, assessment of the JNKI-1D-TAT peptide, when administered 1 or 2 hours after reperfusion after 90 minutes of MCAO, also did not improve histological or functional outcomes at 48 hours after occlusion. This study is the first to evaluate the efficacy of PYC36D-TAT and JNKI-1D-TAT using the SH rat, which has recently been shown to be more sensitive to AMPA receptor activation rather than to NMDA receptor activation after cerebral ischemia, and which may have contributed to the negative findings. PMID- 21971353 TI - Brain glycogen content and metabolism in subjects with type 1 diabetes and hypoglycemia unawareness. AB - Supercompensated brain glycogen may contribute to the development of hypoglycemia unawareness in patients with type 1 diabetes by providing energy for the brain during periods of hypoglycemia. Our goal was to determine if brain glycogen content is elevated in patients with type 1 diabetes and hypoglycemia unawareness. We used in vivo (13)C nuclear magnetic resonance spectroscopy in conjunction with [1-(13)C]glucose administration in five patients with type 1 diabetes and hypoglycemia unawareness and five age-, gender-, and body mass index matched healthy volunteers to measure brain glycogen content and metabolism. Glucose and insulin were administered intravenously over ~51 hours at a rate titrated to maintain a blood glucose concentration of 7 mmol/L. (13)C-glycogen levels in the occipital lobe were measured at ~5, 8, 13, 23, 32, 37, and 50 hours, during label wash-in and wash-out. Newly synthesized glycogen levels were higher in controls than in patients (P<0.0001) for matched average blood glucose and insulin levels, which may be due to higher brain glycogen content or faster turnover in controls. Metabolic modeling indicated lower brain glycogen content in patients than in controls (P=0.07), implying that glycogen supercompensation does not contribute to the development of hypoglycemia unawareness in humans with type 1 diabetes. PMID- 21971352 TI - Therapeutic high-frequency stimulation of the subthalamic nucleus in Parkinson's disease produces global increases in cerebral blood flow. AB - Chronic, high-frequency electrical stimulation of the subthalamic nuclei (STNs) has become an effective and widely used therapy in Parkinson's disease (PD), but the therapeutic mechanism is not understood. Stimulation of the STN is believed to reorganize neurophysiological activity patterns within the basal ganglia, whereas local field effects extending to tracts adjacent to the STN are viewed as sources of nontherapeutic side effects. This study is part of a larger project investigating the effects of STN stimulation on speech and regional cerebral blood flow (CBF) in human subjects with PD. While generating measures of global CBF (gCBF) to normalize regional CBF values for a subsequent combined analysis of regional CBF and speech data, we observed a third effect of this therapy: a gCBF increase. This effect was present across three estimates of gCBF ranging from values based on the highest activity voxels to those based on all voxels. The magnitude of the gCBF increase was related to the subject's duration of PD. It is not clear whether this CBF effect has a therapeutic role, but the impact of deep brain stimulation on cerebrovascular control warrants study from neuroscience, pathophysiological, and therapeutic perspectives. PMID- 21971354 TI - Cerebral microvascular inflammation in DOCA salt-induced hypertension: role of angiotensin II and mitochondrial superoxide. AB - Angiotensin II-mediated hypertension (HTN) is accompanied by a pro-inflammatory and pro-thrombotic state in the cerebral microvasculature. Whether comparable phenotypic changes are elicited in other models of HTN remains unclear. Using wild-type mice with deoxycorticosterone acetate (DOCA) salt-induced HTN and intravital microscopy, we observed significant increases in the adhesion of both leukocytes and platelets in cerebral venules, compared with uninephrectomized control mice, without an accompanying increase in blood-brain barrier permeability. The cell-cell interactions in hypertensive mice were more pronounced after ischemic stroke, but no difference in infarct size was detected. The blood cell recruitment was largely prevented in the following groups of DOCA salt mice: losartan (angiotensin II AT1 receptor blocker) treated, AT1 receptor knockout mice, tempol (a membrane-permeable oxygen radical scavenger) treated, and mito-TEMPO (a mitochondria-targeted antioxidant) treated. A similar pattern of protection was noted in mice subjected to ischemic stroke. The blunted cell recruitment responses were not accompanied by reductions in blood pressure (BP). These findings implicate mitochondria-derived oxygen radicals and angiotensin II in the cerebral inflammation associated with DOCA salt HTN and suggests that BP per se is not a critical determinant of the phenotypic changes that accompany HTN, even after ischemic stroke. PMID- 21971355 TI - Direct stimulation of angiotensin II type 2 receptor enhances spatial memory. AB - We examined the possibility that direct stimulation of the angiotensin II type 2 (AT(2)) receptor by a newly generated direct AT(2) receptor agonist, Compound 21 (C21), enhances cognitive function. Treatment with C21 intraperitoneal injection for 2 weeks significantly enhanced cognitive function evaluated by the Morris water maze test in C57BL6 mice, but this effect was not observed in AT(2) receptor-deficient mice. However, C21-induced cognitive enhancement in C57BL6 mice was attenuated by coadministration of icatibant, a bradykinin B(2) receptor antagonist. Administration of C21 dose dependently increased cerebral blood flow assessed by laser speckle flowmetry and hippocampal field-excitatory postsynaptic potential (f-EPSP) determined by electrophysiological techniques in C57BL6 mice. Furthermore, activation of the AT(2) receptor by C21 promoted neurite outgrowth of cultured hippocampal neurons prepared from fetal transgenic mice expressing green fluorescent protein. Finally, we investigated the pathologic relevance of C21 for spatial learning using an Alzheimer's disease mouse model with intracerebroventricular injection of amyloid-beta (1 to 40). We observed that treatment with C21 prevented cognitive decline in this model. These results suggest that a direct AT(2) receptor agonist, C21, enhances cognitive function at least owing to an increase in CBF, enhancement of f-EPSP, and neurite outgrowth in hippocampal neurons. PMID- 21971356 TI - Association of HIV neutralizing antibody with lower viral load after treatment interruption in a prospective trial (A5170). AB - OBJECTIVE: We investigated the impact of neutralizing antibodies (NAbs) on CD4 T cell count and viral load in a cohort of HAART recipients who underwent extended structured treatment interruption. DESIGN: Substudy of NAb in the AIDS Clinical Trials Group 5170 trial. METHODS: Early plasma samples from 50 volunteers who discontinued HAART were evaluated in a peripheral blood mononuclear cell-based neutralization assay against a panel of four subtype B primary isolates. RESULTS: We found that high-titer (90% inhibitory dose > 500) NAb against two or more isolates was associated with reduced viral load (P = 0.003 at 12-week posttreatment interruption). This effect faded with time, losing significance (P = 0.161) by study conclusion. Participants possessing the highest NAb levels against individual isolates appeared more likely to have lower viral loads with the association gaining significance against the R5-tropic primary isolate US1 (P = 0.005). There was no association between broader neutralization and CD4 T-cell slope over time. CONCLUSION: The data suggest that high-titer NAb responses at the time of treatment interruption are associated with reduced viral load over time, but not CD4(+) T-cell decline. PMID- 21971358 TI - HIV-1 induces NALP3-inflammasome expression and interleukin-1beta secretion in dendritic cells from healthy individuals but not from HIV-positive patients. AB - OBJECTIVE: NALP3-inflammasome is an innate mechanism, alternative to type-1 interferon, which is able to recognize nucleic acids and viruses in the cytoplasm and to induce pro-inflammatory response. Here, we hypothesized the involvement of inflammasome in the early defense against HIV-1 and in the full maturation of dendritic cells: for this, we evaluated the response of dendritic cells pulsed with HIV-1 in terms of inflammasome activation in healthy donors. Moreover, inflammasome response to HIV was evaluated in HIV-infected individuals. DESIGN AND METHODS: Monocyte-derived dendritic cells isolated from 20 healthy individuals (HC-DC) and 20 HIV-1-infected patients (HIV-DC) were pulsed with alditrithiol-2-inactivated HIV-1. We then analyzed inflammasome genes expression and interleukin-1beta (IL-1beta) secretion. RESULTS: In HC-DC, HIV-1 induced higher NLRP3/NALP3 mRNA expression compared with other inflammasome genes such as NALP1/NLRP1 or IPAF/NLRC4 (P < 0.001). This augmented expression was accompanied by CASP1-increased and IL1B-increased mRNA levels and by a significant increment of IL-1beta secretion (P < 0.05). Otherwise, HIV-1 failed to activate inflammasome and cytokine production in HIV-DC. HIV-DC showed an increased NLRP3/NALP3 basal expression, suggesting a chronic inflammatory profile of patients' immune cells. CONCLUSION: HIV-1 was able to induce a NALP3-inflammasome response in healthy individuals, indicating that this inflammasome could play a role in the first steps of HIV-1 infection; the consequent inflammatory process may be important for directing host immune response against the virus and/or disease progression. HIV-DC seemed to be chronically activated, but unresponsive against pathogens. Our findings could be of interest considering the ongoing research about dendritic cell manipulation and therapeutic strategies for AIDS involving dendritic cell-based immune-vaccines. PMID- 21971357 TI - Early antiretroviral therapy in HIV-1-infected infants, 1996-2008: treatment response and duration of first-line regimens. AB - OBJECTIVE: To investigate virological and immunological response to antiretroviral therapy (ART), and predictors of switching and interrupting treatment among infants starting ART across Europe. DESIGN: Cohort study. METHODS: Nine cohorts from 13 European countries contributed data on HIV-infected infants born 1996-2008 and starting ART before age 12 months. Logistic and linear regression, and competing risks methods were used to assess predictors of virological (viral load <400 copies/ml) and immunological (change in CD4 Z-score) response, switching to second-line ART and treatment interruptions with viral load less than 400 copies/ml. RESULTS: A total of 437 infants were followed for median 5.9 (interquartile range 2.3-7.6) years after starting ART; 30% had an AIDS diagnosis prior to ART initiation. 53% had suppressed viral load <400 copies/ml at 12 months in 1996-1999, increasing to 77% in 2004-2008. Virological and immunological responses at 12 months varied by initial ART type (P < 0.001 and P = 0.03, respectively), with four-drug nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens being superior [virological response <400 copies/ml adjusted odds ratio = 3.00, 95% confidence interval (CI) 1.24-7.23; mean increase in CD4 Z-score coefficient = 0.64, 95% CI 0.10-1.17] to both three drug NNRTI-based (reference) and boosted protease inhibitor regimens which were similar. Rates of switching to second-line ART were lower among children starting four-drug NNRTI-based and boosted protease inhibitor-based regimens compared with three-drug NNRTI regimens (P = 0.03). Sixty five percent of infants remained on first-line ART without treatment interruption after 5 years. CONCLUSION: Effective and prolonged responses to first-line ART can now be achieved in infants starting early ART outside trial settings. Superior responses to four drug NNRTI compared with boosted protease inhibitor or three-drug NNRTI regimens need further evaluation, as does treatment interruption following early ART. PMID- 21971359 TI - Lessons learned in the deployment of a HIV counseling and testing management information system on a new project. AB - OBJECTIVE: To share our experience on how we used simple but detailed processes and deployed a management information system on a new HIV counseling and testing (HCT) project in Nigeria. DESIGN: The procedures used in this study were adopted for their strength in identifying areas of continuous improvement as the project was implemented. METHODS: We used an iterative brainstorming technique among 30 participants (volunteer counselors and project management staff) as well as iterative quality audits to identify several limitations to the success of the project and to propose solutions. We then implemented the solutions and reevaluated for performance. Findings from the evaluations were then reintroduced into the brainstorming and planning sessions. RESULTS: Several limitations were identified with the most prominent being the poor documentation of records at the site and the lack of a document transfer trail for audit purposes. CONCLUSION: Communication, cohesion and team focus are necessary to achieve success on any new project. Institutionalizing routine HIV behavioral surveillance using data collected at HCT will help in streamlining interventions that will be evidence based. PMID- 21971361 TI - Quinolino-triazole linked gold nanoparticles as sensitive 'turn-on' fluorescent Cd(2+) probes. AB - Quinoline derivatives were brought into the surface of gold nanoparticles (Au NPs) through click chemistry. The fluorescence was quenched by Au NPs because of electron transfer between Au NPs and quinoline. However, upon addition of Cd(2+) to the quinoline-triazole Au NP solution, it exhibited an effective switch-on fluorescence response, owing to the coordination between quinoline and Cd(2+) which can efficiently block the electron transfer. What's more, the fluorescent sensor can effectively detect Cd(2+) in aqueous solution with a detection limit of 1.0 * 10(-5) M. PMID- 21971363 TI - Lifetime of vibrational levels from Fourier grid calculations: RbCs example. AB - We present systematic calculations of the lifetimes of vibrational levels of excited Rb(5s)Cs(6p(1/2)) 0(+) electronic states. We show that a precise description of the variation with the internuclear distance of the transition dipole moment between electronic states is essential. It is also crucial to account precisely for the spin-orbit coupling between the Rb(5s)Cs(6p) A (1)Sigma(+) and b (3)Pi states. We describe the general trends of the probability of formation of stable molecules in the Rb(5s)Cs(6s) X (1)Sigma(+) and a (3)Sigma(+) electronic states, through radiative decay from the 0(+)v' levels, together with the branching ratios for the obtention of singlet or triplet molecules, stable with respect to dissociation. Furthermore, this analysis allows us to demonstrate the efficiency of the Mapped Fourier Grid Hamiltonian Representation method (MFGHR) to determine rigorously the energy variation, throughout the continuous part of the spectrum, of the density of an observable connecting bound vibrational levels and continuum states. The resolution in energy can be adapted to the studied problem through a judicious choice of the grid parameters. PMID- 21971360 TI - Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance. AB - OBJECTIVES: Raltegravir is the first integrase strand transfer inhibitor approved for treating HIV-1 infection. Although emerging data suggest that raltegravir may also be useful for HIV-2 treatment, studies addressing the in-vitro susceptibility of HIV-2 to raltegravir are scarce, and the genetic pathways leading to raltegravir resistance in HIV-2 have not been adequately characterized. Our objectives were to directly compare the susceptibilities of HIV-1 and HIV-2 to raltegravir and to examine the role of mutations in HIV-2 integrase in emergent raltegravir resistance. MATERIALS AND METHODS: Single-cycle and spreading infection assays were used to quantify the sensitivities of wild type HIV-1 and HIV-2 strains to raltegravir. HIV-2 integrase mutants were constructed by site-directed mutagenesis, and the replication capacities and raltegravir susceptibilities of the resultant variants were analyzed in single cycle assays. RESULTS: Raltegravir showed comparable activity against wild-type HIV-1 and HIV-2 in both single-cycle and spreading infections, with EC(50) values in the low nanomolar range. Amino acid changes Q148R and N155H individually conferred resistance to raltegravir (14-fold and seven-fold, respectively), whereas the Y143C replacement had no statistically significant effect on raltegravir sensitivity. The combination of Q148R with N155H resulted in high level raltegravir resistance (>1000-fold). In addition, all HIV-2 integrase variants tested showed impairments in replication capacity. CONCLUSION: Our data support clinical studies of raltegravir for treating HIV-2 infection and show that the Q148R and N155H changes alone are sufficient for raltegravir resistance in HIV-2. Further efforts are needed to improve access to HIV-2-active antiretrovirals, including raltegravir, in resource-limited areas where HIV-2 is endemic. PMID- 21971364 TI - Glucocorticoid pulsatility and rapid corticosteroid actions in the central stress response. AB - Glucocorticoid hormones are secreted from the adrenal gland in hourly pulses, on top of which a surge can take place after stress. The current review describes how changes in pulse amplitude and frequency have consequences for the transcriptional responsivity of target tissues to stress-induced rises in glucocorticoids, and also how these altered pulse patterns affect neuroendocrine and behavioural responses. The mechanistic underpinning of these often rapid changes of the effects of pulsatility on stress responsivity has been greatly advanced with the discovery of membrane variants of the nuclear mineralocorticoid and glucocorticoid receptors. The new findings qualify glucocorticoid pulsatility and rapid non-genomic actions as important determinants of the allostatic state. PMID- 21971365 TI - Fast, transient cardiac accelerations and decelerations during fear conditioning in rats. AB - The current study reports on a number of heart rate responses observed in rats subjected to a discriminatory Pavlovian fear conditioning procedure. Rats learned that a series of six auditory pips was followed by a footshock when presented alone, but not when the pip series was preceded by a visual safety signal. Each auditory pip in the series evoked a fast transient (<1s) cardiac deceleration. This was the case on both trials followed by shock and on trials not followed by shock. The onset of the safety light evoked a similar fast deceleration. We propose that these transient decelerations are similar to the human Evoked Cardiac Response 1 (ECR1), a brief modest deceleration evoked by simple sensory stimuli that is thought to reflect an early process of stimulus registration. Immediately following these pip-evoked decelerations, modest fast accelerations were observed. These accelerations were larger when the pip series was followed by shock than when it was not followed by shock. We propose a potential linkage between these accelerations and the human acceleratory ECR2 component, which is associated with more elaborate processing following stimulus registration; something likely to take place when the pip series predicts an aversive event. Both the ECR1- and ECR2-like responses were embedded within a slow, gradual heart rate increase across the entire pip series. This tonic increase was significantly larger on trials with footshock and is therefore probably associated with anticipatory fear of the upcoming shock. An additional special type of cardiac response was found to the first pip in the series not preceded by the safety signal; here, a much larger and more sustained deceleration was apparent. This response appears relatable to the prolonged deceleration reported in humans in response to aversive picture content. We discuss the cardiac responses found in rats in the current study in the context of heart rate responses known in the human literature. PMID- 21971367 TI - Heterogeneous reactivity of chlorine atoms with sodium chloride and synthetic sea salt particles. AB - The uptake of chlorine atoms on sodium chloride (NaCl) and synthetic sea salt (SSS) particles was studied using a discharge flow reactor coupled to a molecular beam mass spectrometer. The reactive surfaces were prepared by coating the inner surface of the reactor using two different methods: either by depositing size selected particles on halocarbon wax or by spray depositing thin films using a constant output atomizer. The observed uptake coefficients of Cl on NaCl particles are gamma(NaCl)(Cl) ~ 2 * 10(-2) for size-selected particles or gamma(NaCl)(Cl) ~ 5 * 10(-2) for thin films and for SSS particles gamma(SSS)(Cl) ~ 4 * 10(-3). Heterogeneous recombination of Cl atoms to Cl(2) molecules was observed for the two solid surfaces. The study was performed over the temperature range 258 to 353 K. The temperature dependence of the uptake was observed and the heat of adsorption of Cl on NaCl particles was estimated at Q(ads) = 63 kJ mol( 1) assuming an Eley-Rideal mechanism. The role of surface adsorbed water has also been shown. The atmospheric implications of these findings are discussed briefly. PMID- 21971366 TI - A comparison of activation patterns of cells in selected prefrontal cortical and amygdala areas of rats which are more or less anxious in response to predator exposure or submersion stress. AB - This study had two purposes. First: to compare predator and water submersion stress cFos activation in medial prefrontal cortices (mPFC) and the medial amygdala (MeA). Second: to identify markers of vulnerability to stressors within these areas. Rats were either predator or submersion stressed and tested 1.75 h later for anxiety. Immediately thereafter, rats were sacrificed and cFos expression was examined. Predator and submersion stress equally increased anxiety like behavior in the elevated plus maze (EPM) and hole board. To examine vulnerability, rats which were less anxious (LA) and more (highly) anxious (MA) in the EPM were selected from among handled control and stressed animals. LA stressed rats were considered stress non-responsive while MA stressed rats were considered stress responsive. Predator stress, but not submersion stress, activated MeA cFos. CFos expression of mPFC cells was elevated in LA rats and reduced in MA rats in predator stressed animals only, correlating negatively with anxiety. These findings are consistent with data implicating greater mPFC excitability in protection against the effects on affect of traumatic stress. The findings also suggest that this conclusion is stressor specific, applying to predator stress but not submersion stress. Both stressors have been suggested to model hyperarousal and comorbid anxiety aspects of PTSD in humans. Hence the use of these paradigms to identify brain bases of vulnerability and resilience to traumatic stress in PTSD has translation potential. On the other hand, our evidence of stressor specificity of vulnerability/resilience markers raises a caution. The data suggest that preclinical markers of vulnerability/resilience in a given stress paradigm are at best suggestive, and translational value must ultimately be confirmed in humans. PMID- 21971368 TI - Red grape skin and seeds polyphenols: Evidence of their protective effects on endothelial progenitor cells and improvement of their intestinal absorption. AB - SCOPE: To evaluate the ability of grape skin and seeds to protect endothelial progenitor cells (EPC) from oxidative stress induced by hyperglycemia (HG) compared to red wine (RW) and prepare innovative pharmaceutical systems for the oral administration of red grape extract allowing the overcoming of its poor intestinal absorption. METHODS AND RESULTS: Human EPC were characterized by expression of cell surface markers. Cells were incubated with different concentrations of total polyphenols from grape components or RW in the presence or absence of HG. Cell viability, migration, adhesion, and reactive oxygen species (ROS) production were assayed. Intestinal permeation of polyphenols was studied in the absence or presence of a quaternary ammonium-chitosan conjugate (N+(60)-Ch). Grape components and RW increased EPC viability, adhesion and migration, and prevented the HG effect (P < 0.01). ROS production induced by HG was significantly reduced only by grape seed extract and RW (P < 0.01). N+(60)-Ch acted as an effective enhancer of polyphenol permeability across the excised rat intestine. CONCLUSIONS: Red grape components are a source of antioxidant compounds that ameliorate EPC viability and function, while preventing endothelial dysfunction. The use of polycationic chitosan derivatives can promote the absorption of polyphenols across intestinal epithelium, thus increasing their bioavailability and potential therapeutic value in atherosclerosis. PMID- 21971369 TI - Twenty years of drug nanocrystals: where are we, and where do we go? PMID- 21971370 TI - Blood pressure modulation following activation of mast cells by cationic cell penetrating peptides. AB - Short cell penetrating peptides (CPP) are widely used in vitro to transduce agents into cells. But their systemic effect has not been yet studied in detail. We studied the systemic effect of the cell penetrating peptides, penetratin, transportan and pro-rich, on rat hemodynamic functions. Intra-arterial monitoring of blood pressure showed that injection of the positively charged penetratin and transportan in a wide range of concentrations (2.5-320 MUg/kg) caused highly significant transient decrease in the systolic and diastolic blood pressure in a dose dependent manner (p<0.01). Pretreatment with histamine receptors blockers or with cromolyn, a mast cell stabilizing agent, significantly attenuated this effect. Furthermore, in vitro incubation of these both peptides with mast cells line, LAD2, caused a massive mast cell degranulation. In vitro studies showed that these CPP in a wide range of concentrations were not cytotoxic without any effect on the survival of LAD2 mast cell line. In contrast, the less positively charged and proline-rich CPP, pro-rich, had no systemic effects with no effect on mast cell degranulation. Our results indicate that intravenously administrated positively charged CPP may have deleterious consequences due to their induced BP drop, mediated by mast cell activation. Therefore, the major effect of mast cell activation on BP should be considered in developing possible future drug therapies based on the injection of membrane-permeable and positively charged CPP. Nevertheless, lower levels of such CPP may be considered as a treatment of systemic high BP through moderate systemic mast cell activation. PMID- 21971371 TI - Fluoxetine, 17-beta estradiol or folic acid combined with intra-lateral septal infusions of neuropeptide Y produced antidepressant-like actions in ovariectomized rats forced to swim. AB - Folic acid is antidepressant, either alone or combined with several antidepressant drugs. However, the antidepressant-like actions of folic acid combined with intra-lateral septal (LSN) infusions of neuropeptide Y (NPY) in the forced swimming test (FST) have not been tested before. Thus, systemic injections of fluoxetine (20.0mg/kg, P<0.05; s.c.) or 17-beta estradiol (10.0 MUg/rat, P<0.05; s.c.) or oral administrations of folic acid (50.0 mg/kg, P<0.05; 75.0 mg/kg, P<0.05) or NPY intra-LSN (3.0 MUg, P<0.05; 3.5 MUg, P<0.05) reduced immobility of ovariectomized Wistar rats. Subthreshold doses of: folic acid (25.0 mg/kg) or 17-beta estradiol (5.0 MUg/rat, P<0.05) or fluoxetine (15.0 mg/kg, P<0.05; s.c.) combined with subthreshold doses of NPY (2.5 MUg/rat, P<0.05; intra LSN) and these combinations produced antidepressant-like actions; which were canceled by BIBP 3226 (a NPY-Y1 receptor antagonist). It is concluded that folic acid produced antidepressant-like effects probably through the participation of the NPY Y1 receptors found in the lateral septal nuclei. PMID- 21971372 TI - Solitary rectal ulcer: ultrasonographic and magnetic resonance imaging patterns mimicking rectal cancer. AB - The objective of this study was to analyze a series of solitary rectal ulcer syndrome (SRUS) cases initially diagnosed as rectal cancer. We analyzed all the patients (1996-2008) initially referred to our colorectal unit with a diagnosis of rectal cancer but with a final diagnosis of SRUS. Demographic data, the diagnostic work-up, and treatment details were collected in a prospective database and analyzed retrospectively. Out of the 5035 patients registered in the colorectal unit database, 14 (0.28%) had a final diagnosis of SRUS. Nine of them had an initial diagnosis of rectal cancer. Out of these, six were preoperatively staged with endorectal ultrasound and/or magnetic resonance and were therefore analyzed for this study. Endorectal ultrasound was performed in all six patients and rectal cancer was diagnosed in five of them; MRI was performed in four patients and a diagnosis of rectal cancer was assessed in three of them; rectal cancer was finally ruled out in all cases by deep-forceps macrobiopsies. The incidence of misdiagnosis between SRUS and rectal cancer does not decrease with the regular use of imaging methods. Clinical judgment and deep-forceps macrobiopsies are essential in avoiding an erroneous diagnosis. PMID- 21971373 TI - Meta-analysis: efficacy and safety of combination therapy of infliximab and immunosuppressives for Crohn's disease. AB - Although infliximab and immunosuppressives have both proved to be effective in the treatment of Crohn's disease (CD), the efficacy and safety of the combination therapy remained undetermined yet. We performed a meta-analysis to evaluate the efficacy and safety of combination therapy of infliximab and immunosuppressives compared with monotherapy for maintaining steroid-free clinical remission on patients with CD. We searched PubMed, Cochrane Library, and EMBASE. The primary end point was steroid-free clinical remission after induction infusion and in short-term and long-term follow-ups. Total adverse events, severe adverse event, infection, severe infection, infusion reaction, sepsis, tuberculosis, and malignancy also were analyzed. Meta-analysis was carried out by combining the odds ratio (OR) between the combination therapy and monotherapy of the individual studies in a global OR, with statistical heterogeneity tested using the chi2-test and the I2-test. Five studies with eight comparisons involving 1026 patients were included. In an overall analysis, combination therapy was more effective than monotherapy for induction of remission at weeks 10-12 [mean OR=2.50; 95% confidence interval (CI)=1.46-4.30; P=0.0009)] and maintenance of remission at weeks 24-26 (mean OR=2.32; 95% CI=1.75-3.08; P<0.00001) and weeks 48-54 (mean OR=1.83; 95% CI=1.44-2.32; P<0.00001). In all five studies, combination therapy did not increase the risk of total adverse event, severe adverse event, infection, severe infection, and infusion reaction. The combination therapy of infliximab and immunosuppressives was more effective than monotherapy in the induction and maintenance remission of CD, and adverse events did not increase. However, larger clinical trials with longer follow-up are warranted to further assess the efficacy and safety profile of combination therapy. PMID- 21971374 TI - Efficacy of different therapeutic regimens on hepatic osteodystrophy in chronic viral liver disease. AB - BACKGROUND AND AIMS: Metabolic bone disease is common in patients with chronic liver disease. Comparative studies on the efficacies of antiosteoporotic agents in hepatic osteodystrophy have not been conducted yet. The aim of this study was to evaluate the safety and efficacy of different therapeutic regimens on hepatic osteodystrophy. METHODS: Eighty-one patients (mean age 48.9 +/- 10 years; 50 cases with chronic viral hepatitis and 31 patients with cirrhosis) were enrolled in the study. Treatment groups consisted of 61 patients who had reduced T scores in at least one region, selected randomly and treated for 1 year with vitamin D 400 IU, calcitonin 200 IU, alendronate 10 mg, alendronate 70 mg, or risedronate 5 mg. An untreated group consisting of 20 patients who had no reduction in T scores was followed up during the study period. RESULTS: No significant adverse effects, including esophageal variceal hemorrhage, were detected. According to the T score at the end of the first year compared with baseline, significant improvements in bone mineral density were observed at all regions with alendronate 70 mg; improvements at the lumbar spine (LS) and distal radius regions with alendronate 10 mg; at the LS and distal radius regions with risedronate; at the LS region with calcitonin; and at the femoral neck region with vitamin D. CONCLUSION: All therapeutic regimens seemed to be safe, and oral biphosphonates were the most effective in preventing both cortical and trabecular bone loss in patients with chronic viral liver disease. Larger studies with longer follow-up are warranted in hepatic osteodystrophy of chronic viral liver diseases. PMID- 21971376 TI - Ethanolamine oleate in resistant idiopathic achalasia: a novel therapy. AB - OBJECTIVES: Idiopathic achalasia (IA) is a chronic disease without definite therapy. Ethanolamine oleate (EO) has multiple biological effects, including inflammatory activities. We investigated the efficacy of EO injection in selected patients with IA. METHODS: One hundred and thirty-six patients with IA were evaluated prospectively. We evaluated the efficacy of EO injection in 13 patients with IA that are resistant to or a poor candidate of pneumatic balloon dilation and/or cardiomyotomy at the Digestive Disease Research Center, Shariati Hospital, Tehran, as the major referral center for achalasia in Iran in an interventional study. Diluted EO was injected in a divided dose into each of four quadrants of lower esophageal sphincter, using a standard sclerotherapy needle. Injection was repeated at 2 and 4 weeks after first injection. The patients were evaluated with achalasia symptom score (ASS) and timed barium esophagogram (TBE) before and after injections. Good response was defined as a decrease in ASS of at least 50% of baseline and decrease in height and volume of barium of at least 50% of baseline in TBE, at 1.5 months after the last injection. Side-effects were recorded. RESULTS: All patients (13 cases) had good ASS (decreased, >= 50%) and good TBE (decreased in height and volume of barium, >= 50%) response rate. The mean ASS decreased from 11.38 (+/- 1.5) to 3.23 (+/- 1.96) at 1.5 months after the last injection (P=0.001). The mean volume of barium in TBE decreased from 81.38 ml (+/- 51.11) to 40.69 ml (+/- 61.22) at 1.5 months after the last injection (P=0.016). The mean duration of follow-up was 17.83 (+/- 1.12) months. Symptoms of six patients relapsed; all of them were treated effectively with reinjection. CONCLUSION: This study indicates that EO is well tolerated and potentially effective in patients with IA that might be explained by the local inflammatory properties of EO. As presented data are too preliminary to support the routine use of EO in the treatment of all patients with IA; its use in selected cases can be considered. PMID- 21971375 TI - The study of relationship between neutropenia and infection during treatment with peginterferon alpha and ribavirin for chronic hepatitis C. AB - OBJECTIVE: Neutropenia is frequent during treatment of chronic hepatitis C (CHC) with peginterferon and ribavirin. It remains unclear whether neutropenia is associated with infection in CHC. The aim was to study the relationship between neutropenia and infection during treatment with peginterferon and ribavirin for CHC. METHODS: A retrospective cohort on 399 patients treated with peginterferon alpha and ribavirin derived from our hospital database was conducted. The occurrence of infections and their relationship to neutropenia were investigated. Potential risk factors for infection were identified by multivariate analysis. RESULTS: During treatment, neutropenia [absolute neutrophil counts (ANC) <1.5 * 109/l] occurred in 251 patients, mild neutropenia [ANC (0.75-1.5) * 109/l] occurred in 132 patients, moderate neutropenia [ANC (0.50-0.75) * 109/l] occurred in 103 patients, and severe neutropenia (ANC<0.50 * 109/l) occurred in 16 patients. Eighty infections (20.1%) occurred, 14 infections (17.5%) were defined as severe. There was no significant difference in infection rate between patients with and without moderate and severe neutropenia (21.0%, 25/119 vs. 19.6%, 55/280; chi2=0.097, P=0.755). There was no significant difference in infection rate between patients with and without peginterferon dose modifications (21.5%, 31/144 vs. 19.2%, 49/255; chi2=0.307, P=0.580). In multivariate logistic regression analysis, the independent factors associated with infection were age (P=0.021), diabetes (P=0.004), and cirrhosis (P=0.012). CONCLUSION: Infections during treatment with peginterferon alpha and ribavirin for CHC are not associated with neutropenia. The independent factors associated with infection are age, diabetes, and cirrhosis. PMID- 21971377 TI - Endotoxin and tumor necrosis factor-receptor levels in portal and hepatic vein of patients with alcoholic liver cirrhosis receiving elective transjugular intrahepatic portosystemic shunt. AB - BACKGROUND/AIMS: In cirrhosis portal hypertension can promote bacterial translocation and increase serum endotoxin levels. Vice versa, endotoxin aggravates portal hypertension by induction of systemic and splanchnic vasodilation, and by triggering hepatic inflammatory response via tumor necrosis factor alpha (TNFalpha). However, the hepatic elimination of endotoxin in cirrhotic patients with severe portal hypertension, in the absence of acute complications, has not been investigated so far. METHODS: Twenty patients with alcoholic liver cirrhosis received transjugular intrahepatic portosystemic shunt at an event-free interval for either refractory ascites or recurrent bleeding. During the transjugular intrahepatic portosystemic shunt procedure portal and hepatic venous blood samples were obtained and endotoxin levels were measured by a chromogenic limulus-assay. In 16 of these patients an enzyme-linked immunosorbent assay was used to measure levels of the soluble TNFalpha-receptors sTNF-R55 and sTNF-R75. RESULTS: Portal venous endotoxin levels correlated with portal vein velocity (P=0.03) and arterial systolic blood pressure (P=0.007). Portal endotoxin levels correlated with portal venous sTNF-R75-levels (P=0.039; r=0.521) and hepatic venous sTNF-R55-levels (P=0.009; r=0.669). Hepatic venous levels of both sTNF-R55 and sTNF-R75 correlated directly with the model for end stage liver disease-score, and inversely with cholinesterase. However, we did not find significant differences in endotoxin levels nor in sTNF-R55-levels and sTNF R75-levels between portal and hepatic venous blood. CONCLUSION: Endotoxin levels correlated with hemodynamic derangement in cirrhotic severe portal hypertension, and with levels of soluble TNFalpha-receptors. Soluble TNFalpha-receptor levels correlated with the severity of liver dysfunction. However, in this study an endotoxin concentration gradient across the liver was absent, suggesting negligible primary hepatic endotoxin elimination in the absence of complications. PMID- 21971378 TI - Clinical efficacy and safety of lactulose for minimal hepatic encephalopathy: a meta-analysis. AB - OBJECTIVE: To evaluate the clinical efficacy of lactulose in patients with minimal hepatic encephalopathy (MHE). METHODS: Randomized controlled trials (RCTs) comparing lactulose with placebo or with no intervention in the management of MHE that were conducted from January 1990 to July 2011 were searched from MEDLINE, EMBASE, SCI, Cochrane Controlled Trials Register, and China Biological Medicine Database. Studies with a Jadad score higher than 3 were included in the meta-analysis and evaluated using RevMan5.0 software for relative risk (RR) or weighted mean difference (WMD) with 95% confidence intervals (95% CI). Sensitivity analysis was performed on the ethnical differences and quality of the trials. Publication bias was observed using an inverted funnel plot. RESULTS: Nine studies with 434 patients were included in the meta-analysis. Compared with placebo or no intervention, lactulose significantly reduced the risk of no improvement in neuropsychological tests (RR: 0.52, 95% CI: 0.44-0.62, P<0.00001), the time required for the completion of the number connection test-A (WMD: 26.95, 95% CI: -37.81 to -16.10, P<0.00001), and the mean number of abnormal neuropsychological tests (WMD: -1.76, 95% CI: -1.96 to -1.56, P<0.00001). Furthermore, the meta-analysis also showed that lactulose prevented the progression to overt hepatic encephalopathy (RR: 0.17, 95% CI: 0.06-0.52, P=0.002), reduced blood ammonia levels (WMD: -9.89 umol/l, 95% CI: -11.01 to 8.77 umol/l, P<0.00001), and improve health-related quality of life (WMD: -6.05, 95% CI: -6.30 to -5.20, P<0.00001). However, no significant difference was observed in the mortality of patients with MHE (RR: 0.75, 95% CI: 0.21-2.72, P=0.66), and lactulose significantly increased the incidence of diarrhea (RR: 4.38, 95% CI: 1.35-14.25, P=0.01). CONCLUSION: Lactulose has significant beneficial effects for patients with MHE compared with placebo or no intervention. PMID- 21971379 TI - Persistent organic pollutant concentrations in first birth mothers across Mexico. AB - This project was initiated by the North America Commission for Environmental Cooperation (CEC). Its main purpose was to obtain an initial profile on pregnant woman's exposure to persistent organic pollutants (POPs) in North America (Canada, the United States and Mexico). Persistent organic pollutants are transferred to the fetus via the placenta during the pregnancy or to the infant via maternal milk; therefore, the pregnant woman's body burden is important because of the higher exposures and potential health effects in the fetus and infant. This paper presents the results from 240 pregnant women in 10 Mexican cities, and includes the concentrations of various POPs such as polychlorinated biphenyls (PCBs), organochlorine pesticides and polychlorinated dibenzo dioxins and furans (PCDDs and PCDFs) in maternal plasma. We found concentrations of p,p' DDE in maternal samples from Coatzacoalcos to be ~60% higher than those found in Ciudad Obregon, which had the second highest concentration. Pregnant women from Merida had higher mean concentrations of PCBs than all women in other regions. Results for PCDDs and PCDFs plus dioxin-like PCBs data were only available on the basis of composite samples, and their concentrations are similar in most cities except for Coatzacoalcos, which had more than double the concentration found in other cities. Although this study provides useful information on the variability of POPs in specific populations and possible regional/local differences, these results cannot be generalized to the entire Mexican population because of differences in age, gender, sources of exposure and nonrandom nature of the sample. PMID- 21971380 TI - High levels of 1-hydroxypyrene and hydroxyphenanthrenes in urine of children and adults from Afghanistan. AB - Among a health cooperation project, we had the opportunity to study the internal polycyclic aromatic hydrocarbon (PAH) exposure of residents from urban and rural areas in Afghanistan. Urine samples from 13 children (age 2.0-9 years) and 42 adults (age 20-65 years) were collected. A total of 25 participants were from Kabul, and 30 participants lived in a rural area. The determination of 1 hydroxypyrene and hydroxyphenanthrenes was carried out by high performance liquid chromatography and fluorescence detection. Median (range) were as follows (n=55): 1-hydroxypyrene 1646 ng/l (71-16,288 ng/l) and sum of 1-, 2- and 9-, 3-, 4-OH phenanthrenes 3602 ng/l (116-19,670 ng/l). These results indicate a high PAH exposure, compared with the general population in more developed countries. The levels of 1-hydroxypyrene in urine of women (all non-smokers) from the rural area were higher than those from Kabul (N, median, range): rural 15, 2095, 334-11,357 ng/l; Kabul 11, 748,137-5332 ng/l. All households from the rural area used open fires for cooking and energy. We conclude that populations in low-developed countries may be at special risk to increased PAH exposure due to inadequate control of air pollution from car emissions and due to burning of biomass fuels for cooking and household energy. PMID- 21971381 TI - An MDAdvisor interview with Heather Howard, Commissioner of the New Jersey Department of Health and Senior Services. Interviewed by Paul J. Hirsch, MD, Patricia A. Costante and Pete Cammarano. PMID- 21971382 TI - Building stronger hospitals in the Garden State. PMID- 21971383 TI - The opportunity for New Jersey to lead national health reform: a political perspective. PMID- 21971384 TI - Protecting medicare for doctors and seniors. PMID- 21971385 TI - Patients' time: the forgotten cost. PMID- 21971386 TI - Pandemic influenza planning is shared responsibility. PMID- 21971387 TI - Clinical integration: the future paradigm of healthcare delivery for physicians. PMID- 21971388 TI - The legacies of Dr. Jokichi Takamine. PMID- 21971389 TI - Improving the complex doctor-patient relationship. PMID- 21971390 TI - Cultural competency and medical malpractice risk: transformations in the standard of care? PMID- 21971391 TI - Roth IRAs should you be planning for 2010? PMID- 21971392 TI - Development and validation of the stanford binet-5 rarely missed items-nonverbal index for the detection of malingered mental retardation. AB - Current research suggests that effort indices designed for the detection of malingered neurocognitive functioning do not have adequate sensitivity or specificity for use in cases where malingered mental retardation (MR) is the issue. Therefore, development and validation of reliable, objective measures for the detection of malingered MR have become imperative for both forensic and disability cases in recent years. The purpose of this study was to develop and validate an embedded malingering index for the Stanford Binet Intelligence Scales, Fifth Edition. Data from individuals in the SB5 standardization sample, who had intellectual deficits in the MR range, were used. Items that were rarely missed by the MR sample were pooled and validated using a sample of 54 college students asked to feign MR. Nonverbal items that were missed significantly more frequently by the malingering "analog MR sample" were retained and composed the Stanford Binet Rarely Missed Items-Nonverbal (SBRMI-NV) index. When only individuals who successfully malingered MR (FSIQ < 71) were included, sensitivity of 0.88 and specificity of 1.00 were obtained. Results indicate that although the SBRMI-NV needs further validation, it shows great promise in the detection of malingered MR. PMID- 21971393 TI - The potential benefits and the role of cerebral monitoring in carotid endarterectomy. AB - PURPOSE OF REVIEW: The benefit of carotid endarterectomy (CEA) in patients with symptomatic severe carotid stenosis is highly dependent on the perioperative stroke rate. Cerebral monitoring plays an important role in reducing the perioperative stroke rate as it allows detection of the main causes of perioperative stroke, being embolism, intraoperative hypoperfusion and postoperative hyperperfusion syndrome. However, some physicians doubt about the benefit of cerebral monitoring and consider it costly and time consuming. The aim of this review is to provide an overview of the available cerebral monitoring modalities and their role in CEA. RECENT FINDINGS: Electroencephalography, transcranial Doppler, stump pressure and sensory-evoked potentials, are known and used for years. Near-infrared spectroscopy is a relatively new valuable technique, as it is noninvasive, easy to apply and applicable in all CEA patients, but remains to be validated. SUMMARY: In our opinion, cerebral monitoring during CEA is essential because it provides direct information regarding new neurological deficits, which might otherwise be missed. Intraoperative cerebral monitoring provides immediate feedback to the treating physician allowing prompt correction in tissue handling. Several monitoring modalities are available for cerebral monitoring in CEA, but no single test is comprehensive. Therefore, a combination of several monitoring modalities with each specific strength not only during but also after CEA is recommended to cover all needs and reduce the perioperative stroke rate. PMID- 21971394 TI - Limitations of anaesthesia depth monitoring. AB - PURPOSE OF REVIEW: We critically review brain function monitors based on the processed electroencephalogram with regards to signal quality, artefacts and other limitations in clinical performance. RECENT FINDINGS: Several studies have been showing that depth of anaesthesia monitors based on processed electroencephalogram has limitations that can lead to a wrong interpretation of the level of anaesthesia. Processed electroencephalogram indices can be altered by nonanaesthetic influences ranging from artefacts that affect signal quality and signal processing, adverse effects of some anaesthetic and nonanaesthetic drugs, neuromuscular blocking agents to conditions inherent to the patient such as cerebral tumours, brain ischemia and temperature. SUMMARY: Clinicians should be aware of the several limitations of the commercial devices intending to monitor the depth of anaesthesia, which may not reflect the real underlying level of unconsciousness. PMID- 21971395 TI - Does depth of anesthesia monitoring improve postoperative outcomes? AB - PURPOSE OF REVIEW: Devices using the electroencephalogram to estimate anesthetic depth have been available since 1996. Despite the use of these monitors for over a decade, there is little agreement among clinicians about the need for or value of depth of anesthesia monitoring. Since the majority of the studies evaluating the impact of depth of anesthesia monitoring on postoperative outcomes have utilized the bispectral index (BIS Covidian), this manuscript will focus on studies with this device. This review will evaluate the evidence that BIS monitoring can improve long-term outcomes. RECENT FINDINGS: BIS-guided anesthesia can reduce the incidence of awareness with recall in high-risk patients, but a recent study found that anesthetic management directed by an end-tidal anesthetic agent concentration protocol is equally effective, and probably less expensive. Deep anesthesia (BIS < 45) during the intraoperative period is associated with increased postoperative mortality, but this relationship may be an epiphenomenon rather than causal. SUMMARY: There is growing concern that anesthetic management and even specific anesthetic agents may worsen outcomes in high-risk patients. There is, however, no conclusive evidence that depth of anesthesia monitors can improve outcomes and no evidenced-based reasons for anesthesia providers to change their current practice. PMID- 21971396 TI - Delirium in the postanaesthesia period. AB - PURPOSE OF REVIEW: Delirium is an acute, potentially life-threatening organ dysfunction with an incidence reported to range from 10-70% after surgery. Postoperative delirium was found to be associated with persisting cognitive deficits, increased physical dependence and institutionalization, and increased mortality. It is a condition particularly relevant to patients with increasing age. RECENT FINDINGS: This study summarizes recent works of the past 2 years, giving a brief overview as well as background information with regard to risk factors, impact on outcome parameters, mechanisms of pathophysiology, current use of hospital medication, and prevention and treatment strategies of postoperative delirium. SUMMARY: Delirium may have an impact on patients' outcomes beyond their stay in hospital, depending on preoperative comorbidities. Delirium can be devastating for activity of daily living, cognitive performance and survival. Predisposing factors should be recognized preoperatively; precipitating factors such as preoperative fasting, deep sedation and choice of psychotropic drugs, including sedatives, should be reconsidered. Regular structured delirium screening is the precondition for early detection and treatment. Treatment options include cognitive training programmes, anti-inflammatory measures and antipsychotic drugs. PMID- 21971397 TI - New training strategies for anaesthesia residents. AB - PURPOSE OF REVIEW: This review intends to give an overview of developments in anaesthesia residency training. RECENT FINDINGS: Healthcare institutions are stimulated to improve residency training programmes by worldwide quality assurance movements. Research and literature has increased the comprehension of which factors are needed to stimulate effective learning. Recent studies promote the use of (electronic) portfolios that stimulate and monitor the learning process, simulation for training and assessment purposes, and quality assurance with a focus on the role of the clinical teacher and the learning environment. SUMMARY: Innovations in the field of educational studies have provided us with tools to improve the training of our residents. Portfolio, simulation and quality assurance are among the most prominent developments aimed at creating successful residency programmes. Financial implications of the implementation of educational innovations should, however, be considered. PMID- 21971398 TI - Development of a highly selective cell-permeable ratiometric fluorescent chemosensor for oxorhenium(V) ion. AB - A novel 6-(2-pyridinyl)-5,6-dihydrobenzimidazo[1,2-c]quinazoline (HL) serves as a first-time highly selective and sensitive ratiometric fluorescent chemosensor probe for oxorhenium (ReO(V)) ion in acetonitrile : water = 9 : 1 (v/v) at 25 degrees C. The decrease in fluorescence at 410 nm and increase in fluorescence at 478 nm with an isoemissive point at 444 nm in the presence of ReO(V) ion is accounted for by the formation of mononuclear [ReOL(2)Cl] complex, characterized by physico-chemical and spectroscopic tools. The fluorescence quantum yield of the chemosensor (HL) was only 0.198 at 410 nm, and it increased more than 3-fold in the presence of 2 equiv. of the ReO(V) ion at 478 nm. Interestingly, the introduction of other metal ions and relevant anions caused the fluorescence intensity at 478 nm to be either unchanged or weakened. The fluorescence-response fits a Hill coefficient of 2.088 indicates the formation of a 1 : 2 stoichiometry for the L-ReO(V) complex. In the concentration range of 0-20 MUM of oxorhenium(V) species calibration graph was linear with correlation coefficient (R) of 0.99994 and the calibration sensitivity was found to be 4.0 * 10(-7) M. The cellular image in the confocal microscope clearly indicated the presence of ReO(V) in Candida albicans cells using this chemosensor (HL). PMID- 21971399 TI - Dinuclear silver(I) complexes for the design of metal-ligand networks based on triazolopyrimidines. AB - Silver(I) coordination complexes with the versatile and biomimetic ligands 1,2,4 triazolo[1,5-a]pyrimidine (tp), 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (dmtp) and 7-amine-1,2,4-triazolo[1,5-a]pyrimidine (7atp) all feature dinuclear [Ag(2)(MU-tp)(2)](2+) building units (where tp is a triazolopyrimidine derivative), which are the preferred motif, independently of the counter-anion used. According to AIM (atoms in molecules) and ELF (electron localization function) analyses, this fact is due to the great stability of these dinuclear species. The complexes structures range from the dinuclear entities [Ag(2)(MU tp)(2)(CH(3)CN)(4)](BF(4))(2) (1), [Ag(2)(MU-tp)(2)(CH(3)CN)(4)](ClO(4))(2) (2), [Ag(2)(MU-7atp)(2)](ClO(4))(2) (3) and [Ag(2)(MU dmtp)(2)(CH(3)CN)](PF(6))(ClO(4)) (4) over the 1D polymer chain [Ag(2)(MU CF(3)SO(3))(2)(MU-dmtp)(2)](n) (5) to the 3D net {[Ag(2)(MU(3) tp)(2)](PF(6))(2).~6H(2)O}(n) (6) with NbO topology. PMID- 21971400 TI - Active cognitive lifestyle associates with cognitive recovery and a reduced risk of cognitive decline. AB - Education and lifestyle factors linked with complex mental activity are thought to affect the progression of cognitive decline. Collectively, these factors can be combined to create a cognitive reserve or cognitive lifestyle score. This study tested the association between cognitive lifestyle score and cognitive change in a population-based cohort of older persons from five sites across England and Wales. Data came from 13,004 participants of the Medical Research Council Cognitive Function and Ageing Study who were aged 65 years and over. Cognition was assessed at multiple waves over 16 years using the Mini-Mental State Examination. Subjects were grouped into four cognitive states (no impairment, slight impairment, moderate impairment, severe impairment) and cognitive lifestyle score was assessed as a composite measure of education, mid life occupation, and current social engagement. A multi-state model was used to test the effect of cognitive lifestyle score on cognitive transitions. Hazard ratios for cognitive lifestyle score showed significant differences between those in the upper compared to the lower tertile with a more active cognitive lifestyle associating with: a decreased risk of moving from no to slight impairment (0.58, 95% CI (0.45, 0.74)); recovery from a slightly impaired state back to a non impaired state (2.93 (1.35, 6.38)); but an increased mortality risk from a severely impaired state (1.28 (1.12, 1.45)). An active cognitive lifestyle is associated with a more favorable cognitive trajectory in older persons. Future studies would ideally incorporate neuroradiological and neuropathological data to determine if there is causal evidence for these associations. PMID- 21971401 TI - Gas1 interferes with AbetaPP trafficking by facilitating the accumulation of immature AbetaPP in endoplasmic reticulum-associated raft subdomains. AB - The amyloid-beta protein precursor (AbetaPP) is a type I transmembrane protein that undergoes maturation during trafficking in the secretory pathway. Proper maturation and trafficking of AbetaPP are necessary prerequisites for AbetaPP processing to generate amyloid-beta (Abeta), the core component of Alzheimer's disease senile plaques. Recently, we reported that the glycosylphosphatidylinositol (GPI)-anchored protein growth arrest-specific 1 (Gas1) binds to and interferes with the maturation and processing of AbetaPP. Gas1 expression led to a trafficking blockade of AbetaPP between the endoplasmic reticulum (ER) and the Golgi. GPI-anchored proteins can exit the ER by transiting through raft subdomains acting as specialized sorting platforms. Here, we show that Gas1 co-partitioned and formed a complex with AbetaPP in raft fractions, wherein Gas1 overexpression triggered immature AbetaPP accumulation. Pharmacological interference of ER to Golgi transport increased immature AbetaPP accumulation upon Gas1 expression in these raft fractions, which were found to be positive for the COPII protein complex component Sec31A, a specific marker for ER exit sites. Furthermore, a Gas1 mutant lacking the GPI anchor that could not transit through rafts was still able to form a complex with AbetaPP but did not lead to immature AbetaPP accumulation in rafts. Together these data show that Gas1 interfered with AbetaPP trafficking by interacting with AbetaPP to facilitate its translocation into specialized ER-associated rafts where immature AbetaPP accumulated. PMID- 21971402 TI - Expression of p75(NTR), a marker for basal forebrain cholinergic neurons, in young and aged dogs with or without cognitive dysfunction syndrome. AB - The canine cognitive dysfunction syndrome (CDS) has been identified as a natural model for Alzheimer's disease (AD). We have used unbiased stereology to estimate the total number of basal forebrain cholinergic neurons expressing the nerve growth factor p75(NTR) receptor in young, aged cognitively-unimpaired (CU) and aged cognitively-impaired (CI) dogs. Aged-CI dogs showed a ~20% decrement (p = 0.009) in p75(NTR) neurons compared to both the young and the aged-CU animals. These results suggest that the basal forebrain cholinergic system is affected in dogs with CDS and provide additional support for the use this canine syndrome as a model for AD research. PMID- 21971403 TI - Cerebrospinal fluid soluble amyloid-beta protein precursor as a potential novel biomarkers of Alzheimer's disease. AB - In this report, we confirm our previous findings of increased concentrations of soluble amyloid-beta protein precursor (sAbetaPP) in cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) in a large cohort of patients (n = 314), not overlapping with those of our previous study, and we extend our observations by including a control group of participants with normal cognition. In addition, we investigate the effects of age, the APOEepsilon4 genotype, and the blood-CSF barrier function on the concentrations of sAbetaPPalpha and sAbetaPPbeta. The study participants were categorized according to clinical-neuropsychological criteria, supported by CSF neurochemical dementia diagnostics (NDD) analyses. sAbetaPPalpha concentrations in the AD group (132.0 +/- 44.8) were significantly higher than in the control group (105.3 +/- 37.3, p < 0.0005) but did not differ from the MCI-AD group (138.5 +/- 39.5, p = 0.91). The MCI-AD group differed significantly from the MCI O (97.3 +/- 34.3, p < 0.05) group. There was no difference between the control and the MCI-O groups (p = 0.94). Similarly, sAbetaPPbeta concentrations in the AD group (160.2 +/- 54.3) were significantly higher than in the control group (129.9 +/- 44.6, p < 0.005) but did not differ from the MCI-AD group (184.0 +/- 56.4, p = 0.20). The MCI-AD group differed significantly from the MCI-O (127.8 +/- 46.2, p < 0.05) group. There was no difference between the control and the MCI-O groups (p > 0.99). We observed highly significant correlation of the two sAbetaPP forms. Age and the CSF-serum albumin ratio were significant albeit weak predictors of the sAbetaPPalpha and sAbetaPPbeta concentrations, while carrying the APOEepsilon4 allele did not influenced the levels of the sAbetaPP forms. Taken together, the results strongly suggest that CSF sAbetaPP concentrations may be considered as an extension of already available NDD tools. PMID- 21971404 TI - Modest amyloid deposition is associated with iron dysregulation, microglial activation, and oxidative stress. AB - There is a well-established literature indicating a relationship between iron in brain tissue and Alzheimer's disease (AD). More recently, it has become clear that AD is associated with neuroinflammatory and oxidative changes which probably result from microglial activation. In this study, we investigated the correlative changes in microglial activation, oxidative stress, and iron dysregulation in a mouse model of AD which exhibits early-stage amyloid deposition. Microfocus X-ray absorption spectroscopy analysis of intact brain tissue sections prepared from AbetaPP/PS1 transgenic mice revealed the presence of magnetite, a mixed-valence iron oxide, and local elevations in iron levels in tissue associated with amyloid beta-containing plaques. The evidence indicates that the expression of markers of microglial activation, CD11b and CD68, and astrocytic activation, GFAP, were increased, and were histochemically determined to be adjacent to amyloid-beta containing plaques. These findings support the contention that, in addition to glial activation and oxidative stress, iron dysregulation is an early event in AD pathology. PMID- 21971405 TI - Metabolic syndrome, cognitive performance, and dementia. AB - Obesity, hypertension, dyslipidemia, and insulin resistance have been associated with an increased risk of cognitive impairment or dementia. Together, these risk factors cluster as metabolic syndrome (MetS). The first aim of this systematic review was to identify and critically review studies assessing associations between MetS and cognition, with consideration given both to early cognitive changes and the severe endpoint of dementia. The second aim was to identify and discuss limitations in the literature and subsequent difficulties in drawing conclusions from research to date. Nine studies that assessed cognitive performance and ten studies that estimated incidence of dementia in relation to MetS were identified and appraised. Limitations in the literature include the lack of standardized nomenclature for cognitive variables, the use of multiple MetS definitions, and the difficulty in differentiating the adverse effects of multiple risk factors on cognition. PMID- 21971407 TI - Vitamin E inhibits oxidative stress-induced denaturation of nerve terminal proteins involved in neurotransmission. AB - One characteristic of age-related neurodegeneration is thought to be cognitive deficits caused by oxidative stress. Neurons in the brain are considered to be particularly vulnerable to oxidative stress, leading to neuronal oxidative damage and neurodegenerative disorders such as Alzheimer's disease (AD) and senile dementia. The process of fusing synaptic plasma membranes and synaptic vesicles involves particular proteins, such as the soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor (SNARE) proteins for docking both membranes, and is integral to neurotransmission. To elucidate whether oxidative stress induces denaturation of SNARE proteins, and whether vitamin E can counteract this process, changes in the expression of synaptobrevin, synaptotagmin, SNAP-25, and syntaxin-1 in rat brain nerve terminals were analyzed using an immunoblotting method. The results showed that oxidative stress induced significant reductions in the levels synaptobrevin and synaptotagmin in synaptic vesicles. Similarly, marked decreases in the levels of SNAP-25 and syntaxin-1 in pre-synaptic plasma membranes were also observed. In the absence of oxidative stress, vitamin E deficient rats exhibited similar decreases in these proteins. In contrast, it was found that decreases in SNARE proteins, except for SNAP-25, were not observed in vitamin E-supplemented rats, even when the rats were subjected to oxidative stress. These results suggest that reactive oxygen species generated by oxidative stress are detrimental to neurons, resulting in the oxidation of SNARE proteins, thereby disrupting neurotransmission. Additionally, vitamin E is capable of protecting against such neurodegeneration. PMID- 21971408 TI - Behavioral improvement after chronic administration of coenzyme Q10 in P301S transgenic mice. AB - Coenzyme Q10 is a key component of the electron transport chain which plays an essential role in ATP production and also has antioxidant effects. Neuroprotective effects of coenzyme Q10 have been reported in both in vitro and in vivo models of neurodegenerative diseases. However, its effects have not been studied in cells or in animals with tau induced pathology. In this report, we administered coenzyme Q10 to transgenic mice with the P301S tau mutation, which causes fronto-temporal dementia in man. These mice develop tau hyperphosphorylation and neurofibrillary tangles in the brain. Coenzyme Q10 improved survival and behavioral deficits in the P301S mice. There was a modest reduction in phosphorylated tau in the cortex of P301S mice. We also examined the effects of coenzyme Q10 treatment on the electron transport chain enzymes, the mitochondrial antioxidant enzymes, and the tricarboxylic acid cycle. There was a significant increase in complex I activity and protein levels, and a reduction in lipid peroxidation. Our data show that coenzyme Q10 significantly improved behavioral deficits and survival in transgenic mice with the P301S tau mutation, upregulated key enzymes of the electron transport chain, and reduced oxidative stress. PMID- 21971406 TI - High-intensity physical activity modulates diet effects on cerebrospinal amyloid beta levels in normal aging and mild cognitive impairment. AB - We previously showed that amyloid-beta 1-42 (Abeta(42)) levels in cerebrospinal fluid (CSF) were markedly altered in response to a 4-week dietary intervention in normal aging and mild cognitive impairment (MCI). Here, we re-examined the data to assess whether diet-induced effects on CSF Abeta(42) were modulated by high intensity physical activity (hi-PA). Normal older adults (n = 18, mean age = 68.6 +/- 7.4 y) and adults with amnestic MCI (n = 23, mean age = 68.0 +/- 6.5 y) received a low saturated fat/low glycemic index (LOW) diet or a high saturated fat/high glycemic index (HIGH) diet, and CSF levels of Abeta(42), tau, and IL-8 were measured at baseline and week 4. Pre-study activity levels were assessed using a 7-d questionnaire, and weekly duration of hi-PA was quantified. At baseline, increased hi-PA in normals predicted lower CSF levels of tau (r = 0.54, p = 0.020) and IL-8 (r = -0.70, p = 0.025). Diet-induced effects on CSF Abeta(42) during the intervention study were modulated by hi-PA, and the nature of this effect differed for normals and MCI (ANOVA, p = 0.039). That is, for normal adults, increased hi-PA attenuated the effects of the HIGH diet on CSF Abeta(42) whereas in MCI, increased hi-PA potentiated the effects of the LOW diet. Our results suggest that normal adults who engage in hi-PA are less vulnerable to the pathological effects of an unhealthy diet, while in MCI, the benefit of a healthy diet on Abeta modulation is greatest when paired with hi-PA. Exercise may thus interact with diet to alter pathological processes that ultimately modify risk of Alzheimer's disease. PMID- 21971409 TI - Stepwise preparation and characterization of molecular wires made of zinc octaethylporphyrin complexes bridged by 4,4'-bipyridine on HOPG. AB - Molecular-scale devices can be made using a step-by-step procedure, in a controllable and highly versatile way. In this report, we describe the growth of molecular wires (MW) from zinc (II) octaethylporphyrin (ZnOEP) assembled on highly oriented pyrolytic graphite (HOPG) by a step-by-step approach using 4,4' bipyridine (BP) to bridge the porphyrin units, via coordination of the nitrogen atom to zinc. In order to gain an insight into the molecular self-organization of these wires, we carried out a detailed scanning tunnelling microscopy (STM) analysis of each monolayer, using a solid/liquid interface technique, up to a complete ZnOEP/BP/ZnOEP/BP/ZnOEP-assembled structure. The electrical properties of the MWs were assessed by scanning tunnelling spectroscopy (STS) and by current sensing atomic force microscopy (CS-AFM), showing an increase of electrical resistance with the length of the MW. PMID- 21971410 TI - Being all that you can be: the weighting of potential in assessments of self and others. AB - An accurate assessment of an individual often requires taking their potential into account. Across six studies the authors found that people are more inclined to do so when evaluating themselves than when evaluating others, such that people credit themselves for their perceived potential more than they credit others for theirs. Participants rated potential as a more telling component of the self than of others, and the importance participants placed on their own potential led to attentional biases toward information about their own future potential that did not apply to information about the potential of others. Furthermore, when assessing themselves and other people, participants required more tangible proof that someone else has a given level of potential than they required of themselves, and they relied more on how they would ideally perform in self assessment but more on how others actually performed in judging them. PMID- 21971411 TI - Co-cyprindiol prescribing in a large, rural general practice in England. AB - OBJECTIVES: To describe current co-cyprindiol prescribing in a large, rural general practice in England. To specifically investigate whether co-cyprindiol is prescribed within its license and Medicines and Healthcare products Regulatory Agency (MHRA) guidelines. To investigate the effect of a simple, low-cost intervention on the number and appropriateness of co-cyprindiol prescriptions. METHODS: The computerised medical record system in a 17,435 patient general practice was examined to identify individuals prescribed co-cyprindiol. The medical records for each individual identified were examined to see if they satisfied the MHRA guidelines in co-cyprindiol use. Prescribers were then contacted and sent copies of the MHRA guideline. All patients were invited to attend for review. Prescriptions for co-cyprindiol were then re-audited. RESULTS: Co-cyprindiol comprised 3.4% of total combined oral contraceptive prescriptions. The most common indication was acne (69%). At baseline, the majority of prescriptions did not meet the MHRA guidelines. Prescriptions that did not meet guidelines tended to have been for longer (32 vs 19.5 months). After the intervention, the number of individuals prescribed co-cyprindiol fell (26 vs 12) and the number of prescriptions that met the guidelines increased (30.7% vs 75%). The largest change was a decrease in inappropriate prescriptions for acne. CONCLUSIONS: In this population, co-cyprindiol was rarely prescribed, though its use often contravened guidelines. Simple interventions can increase appropriateness of prescribing. PMID- 21971412 TI - Bombardment induced ion transport--part II. Experimental potassium ion conductivities in borosilicate glass. AB - A new experimental approach for measuring the ionic conductivity of solid materials is proposed. The experiment is based on bombarding an ion conducting sample with an alkali ion beam. This generates a well defined surface potential which in turn causes ion transport in the material. The ion transport is measured at the back side of the sample. The viability of the concept is demonstrated by measuring the temperature dependence of the potassium ion conductivity of a potassium borosilicate glass. The activation energy for the potassium transport is 1.04 eV +/- 0.06 eV. For comparison, conductivity data obtained by impedance spectroscopy are presented, which support the bombardment induced data. PMID- 21971414 TI - A new force field model of 1-butyl-3-methylimidazolium tetrafluoroborate ionic liquid and acetonitrile mixtures. AB - Recently, we introduced a new force field (FF) to simulate transport properties of imidazolium-based room-temperature ionic liquids (RTILs) using a solid physical background. In the present work, we apply this FF to derive thermodynamic, structure, and transport properties of the mixtures of 1-butyl-3 methylimidazolium tetrafluoroborate, [BMIM][BF(4)], and acetonitrile (ACN) over the whole composition range. Three approaches to derive a force field are formulated based on different treatments of the ion-ion and ion-molecule Coulomb interactions: unit-charge, scaled-charge and floating-charge approaches. The simulation results are justified with the help of experimental data on specific density and shear viscosity for these mixtures. We find that a phenomenological account (particularly, a simple scaled-charge model) of electronic polarization leads to the best-performing model. Remarkably, its validity does not depend on the molar fraction of [BMIM][BF(4)] in the mixture. The derived FF is so far the first molecular model which is able to simulate all transport properties of the mixtures, comprising RTIL and ACN, fully realistically. PMID- 21971413 TI - Rottlerin enhances IL-1beta-induced COX-2 expression through sustained p38 MAPK activation in MDA-MB-231 human breast cancer cells. AB - Cyclooxygenase-2 (COX-2) is an important enzyme in inflammation. In this study, we investigated the underlying molecular mechanism of the synergistic effect of rottlerin on interleukin1beta (IL-1beta)-induced COX-2 expression in MDA-MB-231 human breast cancer cell line. Treatment with rottlerin enhanced IL-1beta-induced COX-2 expression at both the protein and mRNA levels. Combined treatment with rottlerin and IL-1beta significantly induced COX-2 expression, at least in part, through the enhancement of COX-2 mRNA stability. In addition, rottlerin and IL 1beta treatment drove sustained activation of p38 Mitogen-activated protein kinase (MAPK), which is involved in induced COX-2 expression. Also, a pharmacological inhibitor of p38 MAPK (SB 203580) and transient transfection with inactive p38 MAPK inhibited rottlerin and IL-1beta-induced COX-2 upregulation. However, suppression of protein kinase C delta (PKC delta) expression by siRNA or overexpression of dominant-negative PKC delta (DN-PKC-delta) did not abrogate the rottlerin plus IL-1beta-induced COX-2 expression. Furthermore, rottlerin also enhanced tumor necrosis factor-alpha (TNF-alpha), phorbol myristate acetate (PMA), and lipopolysaccharide (LPS)-induced COX-2 expression. Taken together, our results suggest that rottlerin causes IL-1beta-induced COX-2 upregulation through sustained p38 MAPK activation in MDA-MB-231 human breast cancer cells. PMID- 21971415 TI - Antibacterial effect of acrylic dental devices after surface modification by fluorine and silver dual-ion implantation. AB - The purpose of the present study was to examine the effectiveness of fluorine and silver ions implanted and deposited into acrylic resin (poly(methyl methacrylate)) using a hybrid process of plasma-based ion implantation and deposition. The surface characteristics were evaluated by X-ray photoelectron spectroscopy (XPS), contact angle measurements, and atomic force microscopy. In addition, an antibacterial activity test was performed by the adenosine-5' triphosphate luminescence method. XPS spectra of modified specimens revealed peaks due to fluoride and silver. The water contact angle increased significantly due to implantation and deposition of both fluorine and silver ions. In addition, the presence of fluorine and silver was found to inhibit bacterial growth. These results suggest that fluorine and silver dual-ion implantation and deposition can provide antibacterial properties to acrylic medical and dental devices. PMID- 21971416 TI - Cell-based resorption assays for bone graft substitutes. AB - The clinical utilization of resorbable bone substitutes has been growing rapidly during the last decade, creating a rising demand for new resorbable biomaterials. An ideal resorbable bone substitute should not only function as a load-bearing material but also integrate into the local bone remodeling process. This means that these bone substitutes need to undergo controlled resorption and then be replaced by newly formed bone structures. Thus the assessment of resorbability is an important first step in predicting the in vivo clinical function of bone substitute biomaterials. Compared with in vivo assays, cell-based assays are relatively easy, reproducible, inexpensive and do not involve the suffering of animals. Moreover, the discovery of RANKL and M-CSF for osteoclastic differentiation has made the differentiation and cultivation of human osteoclasts possible and, as a result, human cell-based bone substitute resorption assays have been developed. In addition, the evolution of microscopy technology allows advanced analyses of the resorption pits on biomaterials. The aim of the current review is to give a concise update on in vitro cell-based resorption assays for analyzing bone substitute resorption. For this purpose models using different cells from different species are compared. Several popular two-dimensional and three-dimensional optical methods used for resorption assays are described. The limitations and advantages of the current ISO degradation assay in comparison with cell-based assays are discussed. PMID- 21971417 TI - Biological performance of hydroxyapatite-biopolymer foams: in vitro cell response. AB - Uncoated and biopolymer-coated nanocrystalline hydroxyapatite (HA) macroporous foams are presented as promising candidates as scaffolds for bone tissue regeneration. To this end, foam degradability, the cytotoxic effects on osteoblast-like cells of foam degradation by-products and biocompatibility with osteoblast-like cells were assayed on the three-dimensional (3-D) foam surface. The results show that the 3-D interconnected architectural design of these HA foams allows excellent osteoblast internalization, proliferation and differentiation, exhibiting adequate colonization over the entire scaffold surface with an appropriate degradation rate without any cytotoxic effects. PMID- 21971418 TI - Co-culturing monocytes with smooth muscle cells improves cell distribution within a degradable polyurethane scaffold and reduces inflammatory cytokines. AB - Activated monocytes can promote inflammation or wound repair, depending on the nature of the implant environment. Recent work showed that a degradable, polar hydrophobic-ionic polyurethane (D-PHI) induced an anti-inflammatory monocyte phenotype. In the current study it is hypothesized that wound-healing phenotype monocytes (activated by D-PHI material chemistry) will promote human vascular smooth muscle cells (hVSMC) to attach and migrate into porous D-PHI scaffolds. hVSMC migration is necessary for hVSMC population of the scaffold and tissue formation to occur, and then, once tissue formation is complete, the monocyte should promote contractile phenotype markers in the hVSMC. hVSMC were cultured for up to 28 days with or without monocytes and analyzed for cell viability, attachment (DNA) and migration. Lysates were analyzed for the hVSMC contractile phenotype markers calponin and alpha-smooth muscle actin (alpha-SMA) as well as urokinase plasminogen activator (uPA; pro-migration marker) using immunoblotting analysis. Histological staining showed that hVSMC alone remained around the perimeter of the scaffold, whereas co-culture samples had co-localization of monocytes with hVSMC in the pores, a more even cell distribution throughout the scaffold and increased total cell attachment (P<0.05). Co-culture samples had higher cell numbers and more DNA than the addition of both single cell cultures. The water-soluble tetrazolium-1 data suggested that cells were not dying over the 28 day culture period. Calponin, also linked to cell motility, was maintained up to 28 days in the co-culture and hVSMC alone, whereas alpha-SMA disappeared after 7 days. Co-cultures on D-PHI showed that monocytes were activated to a wound healing phenotype (low TNF-alpha, elevated IL-10), while promoting uPA expression. In summary, this study showed that, by co-culturing monocytes with hVSMC, the latter showed increased total cell attachment and infiltration into the D-PHI scaffold compared with hVSMC alone, suggesting that monocytes may promote hVSMC migration, a condition necessary for ultimately achieving uniform tissue formation in porous scaffolds. PMID- 21971419 TI - Electrically polarized micro-arc oxidized TiO2 coatings with enhanced surface hydrophilicity. AB - The use of micro-arc oxidation titania (MAO TiO2) coatings to modify titanium surfaces improves the biocompatibility of implant surfaces. To obtain hydrophilic MAO TiO2 coating surfaces electric polarization, which induces surface electric fields in the materials and produces surface charges, was performed in this study. Electric polarization of the MAO TiO2 coatings was confirmed by measuring the thermally stimulated depolarization current. After electric polarization treatment the MAO TiO2 coatings did not exhibit any obvious changes in surface roughness, morphology, or phase components. X-ray photoelectron spectroscopy results indicated that electric polarization resulted in oxidation of the cathodic-faced surfaces and reduction of the anodic-faced surfaces. This result suggests that the existence of a concentration gradient of oxide ions/oxygen vacancies produced the stored space charge in the coatings. Reduction of the deionized water contact angle on the polarized MAO TiO2 surfaces was maintained for longer periods compared with the non-polarized surface. Our study demonstrated that metastable electric fields across the MAO TiO2 coating produced by electric polarization made it durably wettable by reducing the interfacial surface tension between the material and water. PMID- 21971420 TI - Molecular mechanisms involved in the regulation of neuritogenesis by estradiol: Recent advances. AB - This review analyzes the signaling mechanisms activated by estradiol to regulate neuritogenesis in several neuronal populations. Estradiol regulates axogenesis by the activation of the mitogen activated protein kinase (MAPK) cascade through estrogen receptor alpha located in the plasma membrane. In addition, estradiol regulates MAPK signaling via the activation of protein kinase C and by increasing the expression of brain derived neurotrophic factor and tyrosine kinase receptor B. Estradiol also interacts with the signaling of insulin-like growth factor-I receptor through estrogen receptor alpha, modulating the phosphoinositide-3 kinase signaling pathway, which contributes to the stabilization of microtubules. Finally, estradiol modulates dendritogenesis by the inhibition of Notch signaling, by a mechanism that, at least in hippocampal neurons, is mediated by G protein coupled receptor 30. This article is part of a Special Issue entitled 'Neurosteroids'. PMID- 21971421 TI - Comparative proteomics and phosphoproteomics analyses of DHEA-induced on hepatic lipid metabolism in broiler chickens. AB - Dehydroepiandrosterone (DHEA) is a precursor of the adrenocorticosteroid hormones that are common to all animals, including poultry. The study described herein was undertaken to investigate the effect of DHEA on lipid metabolism in broiler chickens during embryonic development and to determine the regulatory mechanisms involved in its physiological action. Treatment group eggs were injected with 50mg DHEA diluted in 50 MUL dimethyl sulfoxide (DMSO) per kg, while control group eggs (arbor acres [AA] fertilized) were injected with 50 MUL DMSO per kg prior to incubation. Liver samples were collected on days 9, 14 and 19 of embryonic development as well as at hatching. Extracted proteins were analyzed by two dimensional gel electrophoresis (2-DE) in combination with western blotting for specific anti-phosphotyrosine. The differential spots were identified by matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) or MALDI-TOF-TOF-MS. Peptide mass fingerprinting (PMF) of the differentially expressed proteins were performed using the MASCOT, Prospector or proFound server. Thirty-seven proteins and twenty-two tyrosine phosphorylation proteins were successfully identified. All 37 proteins and 22 tyrosine phosphorylation proteins exhibited a significant volume difference from the control group. These results demonstrated that DHEA increased the expression and level of tyrosine phosphorylation and sulfotransferase proteins in broilers (at pI 5.9), therefore promoting the biotransformation of DHEA. The expression of apolipoproteinA-I was increased in the DHEA treatment group, which facilitated the conversion of cholesterol to cholesterol esters. Also, DHEA increased the expression of peroxiredoxin-6 and its tyrosine phosphorylation protein levels, thus enhancing its anti-oxidative activity. Furthermore, pyruvate dehydrogenase expression was decreased and the level of its tyrosine phosphorylation proteins increased in the DHEA treatment group. Take together, those data indicate that DHEA reduces the supply of acetyl-CoA by inhibiting the activity of its target enzyme (i.e., pyruvate dehydrogenase), thus affecting both protein synthesis and phosphorylation level and decreasing fat deposition in broiler chickens during embryonic development, which could reflect a physiologically-relevant DHEA fat reduction mechanism in the broiler chicken. PMID- 21971422 TI - Validation of the Prostate Cancer Risk Index (PRIX): a simple scoring system to predict risk of biochemical relapse after radical prostatectomy for prostate cancer. AB - OBJECTIVE: The Prostate Cancer Risk Index (PRIX) is a simple scoring system for risk stratification of clinically localized prostate cancer that relies on three variables: prostate-specific antigen level at diagnosis, Gleason score at biopsy and clinical T stage. The aim of this study was validation of the ability of the PRIX score to predict biochemical relapse after radical prostatectomy in a series of patients from a single Japanese center. METHODS: From 1995 to 2008, 519 patients who underwent radical prostatectomy for clinically localized prostate cancer with no adjuvant therapies were included in the validation cohort. The biochemical relapse-free rate was estimated using the Kaplan-Meier method. The performance of the PRIX score was assessed with Cox proportional hazards regression model, concordance index and a calibration plot. For comparison, the performance of the D'Amico classification was also assessed. RESULTS: Biochemical relapse-free rate continuously decreased as the PRIX score increased. Each 1 point increment in the PRIX score led to an increase in hazard ratio for biochemical relapse. The concordance index of the PRIX score and the D'Amico classification to predict biochemical relapse was 0.719 and 0.730, respectively. The Kaplan-Meier plots and the calibration plots demonstrated the possibility that the PRIX score could present more detailed stratification than the D'Amico classification. CONCLUSIONS: The results of our investigation showed that in Japanese patients treated at a single center, the PRIX score can accurately predict biochemical relapse after radical prostatectomy and demonstrates reasonable calibration. The PRIX score may be one option as a prediction model for biochemical relapse after radical prostatectomy. PMID- 21971423 TI - Cigarette smoking and pancreas cancer risk: an evaluation based on a systematic review of epidemiologic evidence in the Japanese population. AB - OBJECTIVE: Cigarette smoking has been recognized as an important risk factor for pancreas cancer, but the magnitude of the association may vary among geographical areas. Therefore, we reviewed epidemiologic studies on the association between cigarette smoking and pancreas cancer in the Japanese population. METHODS: Original data were obtained from MEDLINE searched using PubMed or from searches of the Ichushi database, complemented with manual searches. Evaluation of associations was based on the strength of evidence ('convincing', 'probable', 'possible' or 'insufficient') and the magnitude of association ('strong', 'moderate', 'weak' or 'no association'), together with biological plausibility as previously evaluated by the International Agency of Research on Cancer. RESULTS: We identified four cohort studies and three case-control studies. All cohort studies consistently showed positive associations between pancreas cancer and cigarette smoking, although statistical significance in each study is variable. Most of the cohort studies consistently showed that cigarette smoking had a dose response relationship with pancreas cancer. One case-control study showed a strong positive association, but the rest did not show any association. Meta analysis of seven studies indicated that a summary estimate for ever smoking relative to never smoking was 1.68 (95% confidence interval: 1.38-2.05). CONCLUSIONS: We conclude that there is convincing evidence that cigarette smoking moderately increases the risk of pancreas cancer in the Japanese population. PMID- 21971424 TI - Influence of cationic lipid composition on gene silencing properties of lipid nanoparticle formulations of siRNA in antigen-presenting cells. AB - Lipid nanoparticles (LNPs) are currently the most effective in vivo delivery systems for silencing target genes in hepatocytes employing small interfering RNA. Antigen-presenting cells (APCs) are also potential targets for LNP siRNA. We examined the uptake, intracellular trafficking, and gene silencing potency in primary bone marrow macrophages (bmMPhi) and dendritic cells of siRNA formulated in LNPs containing four different ionizable cationic lipids namely DLinDAP, DLinDMA, DLinK-DMA, and DLinKC2-DMA. LNPs containing DLinKC2-DMA were the most potent formulations as determined by their ability to inhibit the production of GAPDH target protein. Also, LNPs containing DLinKC2-DMA were the most potent intracellular delivery agents as indicated by confocal studies of endosomal versus cytoplamic siRNA location using fluorescently labeled siRNA. DLinK-DMA and DLinKC2-DMA formulations exhibited improved gene silencing potencies relative to DLinDMA but were less toxic. In vivo results showed that LNP siRNA systems containing DLinKC2-DMA are effective agents for silencing GAPDH in APCs in the spleen and peritoneal cavity following systemic administration. Gene silencing in APCs was RNAi mediated and the use of larger LNPs resulted in substantially reduced hepatocyte silencing, while similar efficacy was maintained in APCs. These results are discussed with regard to the potential of LNP siRNA formulations to treat immunologically mediated diseases. PMID- 21971425 TI - Stabilization of expanded (CTG)*(CAG) repeats by antisense oligonucleotides. AB - Myotonic dystrophy type 1 (DM1) is caused by expansion of a CTG repeat in the gene DMPK. The expansion is highly unstable in somatic cells, a feature that may contribute to disease progression. The RNA expressed from the mutant allele exerts a toxic gain of function, due to the presence of an expanded CUG repeat (CUG(exp)). This RNA dominant mechanism is amenable to therapeutic intervention with antisense oligonucleotides (ASOs). For example, CAG-repeat ASOs that bind CUG(exp) RNA are beneficial in DM1 models by altering the protein interactions or metabolism of the toxic RNA. Because CUG(exp) RNA has been shown to aggravate instability of expanded CTG repeats, we studied whether CAG-repeat ASOs may also affect this aspect of DM1. In human cells the instability of (CTG)(800) was suppressed by addition of CAG-repeat ASOs to the culture media. In mice that carry a DMPK transgene the somatic instability of (CTG)(800) was suppressed by direct injection of CAG-repeat ASOs into muscle tissue. These results raise the possibility that early intervention with ASOs to reduce RNA or protein toxicity may have the additional benefit of stabilizing CTG:CAG repeats at subpathogenic lengths. PMID- 21971426 TI - Uptake, efficacy, and systemic distribution of naked, inhaled short interfering RNA (siRNA) and locked nucleic acid (LNA) antisense. AB - Antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) promise specific correction of disease-causing gene expression. Therapeutic implementation, however, has been forestalled by poor delivery to the appropriate tissue, cell type, and subcellular compartment. Topical administration is considered to circumvent these issues. The availability of inhalation devices and unmet medical need in lung disease has focused efforts in this tissue. We report the development of a novel cell sorting method for quantitative, cell type specific analysis of siRNA, and locked nucleic acid (LNA) ASO uptake and efficacy after intratracheal (i.t.) administration in mice. Through fluorescent dye labeling, we compare the utility of this approach to whole animal and whole tissue analysis, and examine the extent of tissue distribution. We detail rapid systemic access and renal clearance for both therapeutic classes and lack of efficacy at the protein level in lung macrophages, epithelia, or other cell types. We nevertheless observe efficient redirection of i.t. administered phosphorothioate (PS) LNA ASO to the liver and kidney leading to targeted gene knockdown. These data suggest delivery remains a key obstacle to topically administered, naked oligonucleotide efficacy in the lung and introduce inhalation as a potentially viable alternative to injection for antisense administration to the liver and kidneys. PMID- 21971428 TI - Protonating and determining myosmine intactly by association with citrate anion. AB - Myosmine can not be separated from nornicotine, nicotine and anabasine intactly by capillary zone electrophoresis (CZE) with a phosphate buffer. Using citrate solution at pH 6.5 as a CZE buffer, myosmine is protonated intactly by H(+), charged positively and then separated from other tobacco alkaloids on the baseline. Its sensitivity is ten times higher than gas chromatography (GC) with a nitrogen-phosphorus detector (NPD). The mechanism for protonating myosmine intactly is discussed and the utility of the new method is testified, too. PMID- 21971427 TI - Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene / allele-specific silencing of mutant huntingtin. AB - Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG-expansion in the huntingtin gene (HTT) that results in a toxic gain of function in the mutant huntingtin protein (mHTT). Reducing the expression of mHTT is therefore an attractive therapy for HD. However, wild-type HTT protein is essential for development and has critical roles in maintaining neuronal health. Therapies for HD that reduce wild-type HTT may therefore generate unintended negative consequences. We have identified single-nucleotide polymorphism (SNP) targets in the human HD population for the disease-specific targeting of the HTT gene. Using primary cells from patients with HD and the transgenic YAC18 and BACHD mouse lines, we developed antisense oligonucleotide (ASO) molecules that potently and selectively silence mHTT at both exonic and intronic SNP sites. Modification of these ASOs with S-constrained-ethyl (cET) motifs significantly improves potency while maintaining allele selectively in vitro. The developed ASO is potent and selective for mHTT in vivo after delivery to the mouse brain. We demonstrate that potent and selective allele-specific knockdown of the mHTT protein can be achieved at therapeutically relevant SNP sites using ASOs in vitro and in vivo. PMID- 21971429 TI - Which is the best health system in the world? PMID- 21971431 TI - Public health doctors call for House of Lords to reject health bill. PMID- 21971430 TI - Shirley Williams: still a rebel. PMID- 21971432 TI - Secret filming shows fundamental problems in general practice. PMID- 21971433 TI - Mid-Stafforshire chief executive considered suicide after publication of damning report. PMID- 21971434 TI - Influence of opioid choice on mechanical ventilation duration and ICU length of stay. AB - BACKGROUND: The aim of this study was to assess the impact on mechanical ventilation and ICU outcomes of substituting remifentanil for sufentanil, in an analgesia-based sedation protocol. A database of data prospectively collected was retrospectively analyzed. The study was carried out in a 16-bed tertiary-care ICU. METHODS: The study included 1544 mechanically ventilated patients admitted from January 2001 to December 2006. Patients were compared between two consecutive phases. Analgesia-based sedation guidelines were the same, except for the opiate used. The patient-to-nurse ratio (2.5) and ventilator weaning practices remained unchanged. 794 patients were included during the sufentanil phase, and 750 during the remifentanil phase. Remifentanil was associated with significantly less time spent on mechanical ventilation (10 days[3-21] vs. 14 days[3-27], P<0.01) and in the ICU (16 days[3-22] vs. 19 days[4-26], P<0.01). The difference was significant for patients ventilated no longer than four days (P=0.0035) but not for patients ventilated more than four days (P=0.058). Sedation target on the Ramsay scale was reached more often with remifentanil. The use and amount of hypnotic agents in addition to the opiate were significantly lower with remifentanil. The cost of analgesia-based sedation was similar in the sufentanil and the remifentanil group. CONCLUSION: Our study suggests that using a short-acting opiate with short context-sensitive half-life in an analgesia based sedation protocol may significantly decrease the duration of mechanical ventilation and the ICU length of stay even though not significantly in long term sedation, while improving the achievement of sedation goals despite a lower requirement for adjunctive hypnotic agents, with no additional costs. PMID- 21971435 TI - Airway pressure curve: a good tool to measure neural inspiratory time? AB - BACKGROUND: Considerable asynchrony during pressure-support ventilation has been reported. While the beginning of active inspiration is usually identifiable in the airway pressure (Paw) curve (the inspiratory trigger), there is still a need for accurate, non-invasive methods to identify the end of inspiration. To test the hypothesis that inspiration, particularly the end of inspiration, can be estimated from the Paw curve, we compared indirect measurements based on Paw with simultaneous direct electromyography of the diaphragm (EMGdi). METHODS: We prospectively studied 10 patients during the weaning period after cardiac surgery. Inspiratory pressure support was set at 20, 15, 10, and 5 cm H(2)O; 25 respiratory cycles were analyzed at each pressure level. Recording of the electromyogram was obtained with electrodes inserted into the diaphragm during surgery. RESULTS: The start and end of inspiration were identified in the Paw curve in 99% and 98% of the 1000 cycles analyzed, respectively, and were coincident with the electromyogram in 62% and 53% of the cycles, respectively. The inspiratory time estimated from the Paw curve was well correlated (r=0.94, P<0.0001) with the electromyogram. CONCLUSION: The end of neural inspiration (EMGdi) can be easily and with little error recognized from the Paw curve alone in patients with normal ventilatory mechanics who receive pressure-support ventilation. PMID- 21971436 TI - Do on- and off-pump coronary bypass surgery differently affect perioperative peripheral tissue metabolism? AB - BACKGROUND: Microdialysis allows the in-vivo assessment of interstitial fluids. We studied the metabolic status of peripheral tissues (skeletal muscle) in patients undergoing coronary artery bypass surgery on- (CABG) or off-pump (OPCAB). METHODS: Twenty patients candidates to elective coronary bypass surgery were randomly assigned to undergo CABG or OPCAB. A microdialysis catheter was inserted in the left deltoid muscle before surgery and left in place for 24 hours, and metabolic markers of peripheral tissue perfusion (glucose, lactate, pyruvate, glycerol and lactate/pyruvate (L/P) ratio) were assessed before, at the end, and 24 hours after surgery. RESULTS: Preoperative clinical features were similar in both groups. Interstitial levels of glucose and lactate increased over time, being in both groups significantly higher than baseline 24 hours after surgery, whereas glycerol levels did not change over time and between groups. In addition, there was an increase over time of pyruvate levels which were significantly higher in CABG after surgery, whereas L/P ratio was significantly higher in OPCAB 24 hours after surgery. CONCLUSION: Metabolic changes after coronary bypass surgery occur with some differences related to CPB use. Overall, these changes suggest that, after coronary surgery, a certain degree of hypermetabolic state ensues, lasting up to 24 hours after surgery; the postoperative increase in pyruvate levels in CABG patients, together with the changes in L/P ratio occurring only in OPCAB patients implies an higher risk of tissue hypoperfusion/ischemia for patients submitted to OPCAB, although this does not lead to permanent cellular damage, as the markers of this complication (e.g., glycerol) do not change over time. PMID- 21971437 TI - Tramadol and 0.5% levobupivacaine for single-shot interscalene block: effects on postoperative analgesia in patients undergoing shoulder arthroplasty. AB - BACKGROUND: The aim of this study was to evaluate the efficacy of tramadol as an adjuvant to the local anaesthetic solution in patients undergoing shoulder arthroscopy for rotator cuff tear after middle interscalene block (MIB). METHODS: We enrolled 120 patients (ASA I-II), scheduled for arthroscopic surgery for rotator cuff tear. The patients were sedated with midazolam 0.02 mg/kg and haloperidol 2 mg i.v. before performing MIB. All subjects underwent a MIB with 0.4 mL/kg of 0.5% levobupivacaine. After computerized randomization, all patients were allocated in 1 of 3 groups, each including 40 subjects. Group Placebo (Group P) received 0.4 mL/kg of 0.5% levobupivacaine plus isotonic sodium chloride for MIB and isotonic sodium chloride i.m. Group "Perineural Tramadol" (Group TPN) received 0.4 ml/Kg of 0.5% levobupivacaine plus 1.5 mg/kg of tramadol perineurally and isotonic sodium chloride i.m. Group "Intramuscular Tramadol" (Group TIM) received 0.4 ml/Kg of 0.5% levobupivacaine plus isotonic sodium chloride perineurally and 1.5 mg/kg of tramadol i.m. RESULTS: The MIB onset times were not statistically different in the three groups. The duration of analgesia was significantly longer in Groups TPN and TIM, where tramadol was administered, either i.m. or perineurally, compared with the placebo group. A significant statistical difference was found in the duration of analgesia between the group TPN and TIM. CONCLUSION: The addition of tramadol to the local anaesthetic solution administered for MIB provided a longer duration of analgesia compared with placebo and i.m tramadol administration in patients undergoing arthroscopic surgery for rotator cuff tear. PMID- 21971438 TI - Arterial lactate above 2 mM is associated with increased brain lactate and decreased brain glucose in patients with severe traumatic brain injury. AB - BACKGROUND: Lactate fuels cerebral energy-consuming processes and it is neuroprotective. The impact of arterial lactate on brain metabolism determined by microdialysis was investigated retrospectively in patients with severe traumatic brain injury (TBI). METHODS: Cerebral microdialysis (glucose, lactate), neuromonitoring (ICP, CPP, ptiO2, SjvO2) and blood gas data collected in 20 patients during pharmacologic coma were grouped within predefined arterial lactate clusters (<1, 1-2, >2 mM). Microdialysis samples were only taken from time points characterized by normoventilation (paCO2 34.5-42 mmHg), sufficient oxygenation (paO2 >75 mmHg) and hematocrit (>=24%) to exclude confounding influences. RESULTS: Elevated arterial lactate >=2 mM was associated with significantly increased brain lactate which coincided with markedly decreased brain glucose despite significantly increased arterial glucose levels and sufficient cerebral perfusion indirectly determined by normal SjvO2 and ptiO2 values. At elevated arterial lactate levels signs of significantly increased cerebral lactate uptake coincided with markedly decreased cerebral glucose uptake. Infused lactate above 50 mM per 24 hours was associated with significantly decreased cerebral glucose. CONCLUSION: Increased arterial lactate levels were associated with increased cerebral lactate uptake and elevated brain lactate. At the same time brain glucose uptake and brain glucose were significantly reduced. It remains unclear whether arterial lactate is the driving force for the increased cerebral lactate levels or if the reduced glucose uptake also contributed to the increased cerebral lactate levels. Further studies are required to assess the impact of lactate infusion under clinical conditions. PMID- 21971439 TI - Auto-PEEP in respiratory failure. AB - Intrinsic positive end-expiratory pressure (auto-PEEP) is a common occurrence in patients with acute respiratory failure requiring mechanical ventilation. Auto PEEP can cause severe respiratory and hemodynamic compromise. The presence of auto-PEEP should be suspected when airflow at end-exhalation is not zero. In patients receiving controlled mechanical ventilation, auto-PEEP can be estimated measuring the rise in airway pressure during an end-expiratory occlusion maneuver. In patients who trigger the ventilator or who are not connected to a ventilator, auto-PEEP can be estimated by simultaneous recordings of airflow and airway and esophageal pressure, respectively. The best technique to accurately measure auto-PEEP in patients who actively recruit their expiratory muscle remains controversial. Strategies that may reduce auto-PEEP include reduction of minute ventilation, use of small tidal volumes and prolongation of the time available for exhalation. In patients in whom auto-PEEP is caused by expiratory flow limitation, the application of low-levels of external PEEP can reduce dyspnea, reduce work of breathing, improve patient-ventilator interaction and cardiac function, all without worsening hyperinflation. Neurally adjusted ventilatory assist, a novel strategy of ventilatory assist, may improve patient ventilator interaction in patients with auto-PEEP. PMID- 21971441 TI - Off-pump coronary surgery: is it just a surgical matter? PMID- 21971440 TI - Cytochrome P450 polymorphism and postoperative cognitive dysfunction. AB - BACKGROUND: The etiology of postoperative cognitive dysfunction (POCD) remains unclear but toxicity of anesthetic drugs and their metabolites could be important. We aimed to assess the possible association between POCD after propofol anesthesia and various phenotypes owing to polymorphisms in cytochrome P450 encoding genes. METHODS: We included patients who underwent non-cardiac surgery under total intravenous anesthesia with propofol. POCD was identified using a neuropsychological test-battery administered preoperatively, one week, and three months after surgery. Genotyping of CYP2C19*2, *3, CYP2D6*3, *4, *5 and *6 was performed using pyrosequencing, and patients were characterized according to their phenotype as ultra, extensive, intermediate, or poor metabolizers. RESULTS: In total, 337 patients with a median age of 67 years were included. 30 (9.4%) out of the 319 patients who underwent neuropsychological testing at one week had POCD, and 24 out of 307 (7.8%) had POCD at three months. None of the examined CYP2C19, 2D6 alleles, or various phenotypes were significantly associated with POCD. CONCLUSION: Polymorphisms in CYP2C19, or 2D6 genes do not seem to be related to the occurrence of cognitive dysfunction after non-cardiac surgery in patients anesthetised with propofol. PMID- 21971442 TI - Do surprised faces affect infants' attention toward novel objects? AB - Previous research has shown that expressions of fear have an effect on infants' object processing. This event-related potential study addresses the question whether surprised faces affect infants' brain responses to objects in a similar way, as both expressions share a crucial perceptual feature, wide-opened eyes. Three-month and 9-month-old infants were presented with surprised and neutral faces gazing toward objects. Following each face looking toward an object, the object was presented again without the face. Three-month-olds directed an increased attention to objects that were previously gaze cued by a surprised compared with neutral face as indicated by an enhanced negative central component. This replicates earlier findings using fearful compared with neutral faces as stimuli. Nine-month-olds did not show different responses to objects in both conditions. This suggests that surprised faces have the same effect as fearful faces on 3-month-olds', but not on 9-month-olds' object processing. The findings are discussed in terms of social cognitive and visuoperceptual development. PMID- 21971443 TI - Flavin adenine dinucleotide content of quinone reductase 2: analysis and optimization for structure-function studies. AB - Quinone reductase 2 (NQO2) is a broadly expressed enzyme implicated in responses to a number of compounds, including protein kinase inhibitors, resveratrol, and antimalarial drugs. NQO2 includes a flavin adenine dinucleotide (FAD) cofactor, but X-ray crystallographic analysis of human NQO2 expressed in Escherichia coli showed that electron density for the isoalloxazine ring of FAD was weak and there was no electron density for the adenine mononucleotide moiety. Reversed-phase high-performance liquid chromatography (HPLC) of the NQO2 preparation indicated that FAD was not present and only 38% of the protomers contained flavin mononucleotide (FMN), explaining the weak electron density for FAD in the crystallographic analysis. A method for purifying NQO2 and reconstituting with FAD such that the final content approaches 100% occupancy with FAD is presented here. The enzyme prepared in this manner has a high specific activity, and there is strong electron density for the FAD cofactor in the crystal structure. Analysis of NQO2 crystal structures present in the Protein Data Bank indicates that many may have sub-stoichiometric cofactor content and/or contain FMN rather than FAD. This method of purification and reconstitution will help to optimize structural and functional studies of NQO2 and possibly other flavoproteins. PMID- 21971444 TI - Combining RNA-DNA swapping and quantitative polymerase chain reaction for the detection of influenza A nucleoprotein. AB - The detection of proteinaceous antigens generally relies on traditional immunoassays and, more recently, on immuno-PCR (polymerase chain reaction) assays and their derivatives, which do not take advantage of the intrinsic function or binding property of a protein. The RNA-binding nucleoprotein has been shown to be an excellent target for the development of various influenza A diagnostics due to its high antigenicity and the presence of large numbers in the virus. It binds nonspecifically to the sugar-phosphate backbone of RNA as well as to single stranded DNA (ssDNA) in vitro. We decided to take advantage of this property to develop an ssDNA probe for the detection of nucleoprotein by quantitative PCR (qPCR). We found that recombinant influenza A nucleoprotein from avian H5N1 subtype binds strongest to a 74-base-long ssDNA. Two systems, one comprising an antibody-based nucleoprotein capture surface and the other based on direct nucleoprotein adsorption under denaturing conditions, were developed combining the replacement of RNA bound to nucleoprotein by a discrete ssDNA probe and a qPCR for the detection of nucleoprotein in the low picomolar (pM) range. PMID- 21971445 TI - Rubella revisited: where are we on the road to disease elimination in Central Europe? AB - Rubella is a contagious viral disease with few complications except when contracted by pregnant women. Rubella infection in pregnancy can result in miscarriage, stillbirth or an infant born with congenital rubella syndrome (CRS) which comprises deafness, heart disease, cataracts and other permanent congenital manifestations. Clinical diagnosis of rubella is difficult due to overlapping symptoms with many other diseases and confirmation of rubella is not possible without laboratory testing. Effective vaccination programmes are critical to the elimination of rubella and prevention of CRS. Such programmes have been successful in several countries in Europe and around the world. However, rubella outbreaks still occur due to suboptimal vaccine coverage and in the past 10 years rubella has been reported in Central European countries such as Romania and Poland. Over the past decade the elimination of rubella and prevention of congenital rubella infection in Europe has been a high priority for the WHO European Regional Office. In 2010 the WHO regional committee for Europe renewed its commitment to the elimination of rubella and prevention of CRS with a new target of 2015. This paper examines the current situation for rubella and CRS in Central Europe and describes the different rubella vaccination programmes in the region. The Central European Vaccination Advisory Group (CEVAG) recommends that two doses of measles, mumps and rubella vaccine, MMR, should be given to all children. The first dose should be given between 12 and 15 months of age. The second dose can be given between the ages of 21 months and 13 years with the exact age of administration of the second dose depending on the situation specific to each country. All suspected rubella cases should be laboratory confirmed and monitoring systems to detect and investigate cases of CRS should be strengthened. PMID- 21971446 TI - Building on the success of the Expanded Programme on Immunization: enhancing the focus on disease prevention and control. AB - The Expanded Programme on Immunization (EPI) has succeeded in establishing a vaccine delivery system in all low and middle income (LMI) countries. Because EPI has focused on immunization delivery, its major outcome is measured in many countries only as vaccine coverage, not as disease reduction, the real goal of EPI. Monitoring disease reduction requires real-time case-based disease surveillance and appropriate interventions, for which a functional public health infrastructure is needed. If the highest priority for assessing impact of EPI shifts to disease prevention and control from vaccine coverage, the programme may be transformed to one of control of childhood communicable diseases (CCCD), with the potential of expanding the range of diseases of children and adults for control and of integrating all other current vertical (single disease) control efforts with it. EPI provides the essential platform on which CCCD can be built to create a public health infrastructure. PMID- 21971447 TI - Method for electrical characterization of nanowires. AB - The ability to control conductivity in semiconductor nanostructures is often challenged by surface states trapping the majority of the charge carriers. Addressing this challenge requires a reliable method for assessing electrical properties such as carrier concentration and mobility. Unfortunately, here we are facing another challenge, as the Hall effect is geometrically inapplicable to nanowires while the field effect model is also challenged by the geometry of the common nanowire field effect transistor, and can only yield channel mobility which is very different from Hall mobility. In this paper, we propose a method that combines resistivity and photovoltage measurements with a chemical perturbation to the surface to measure carrier concentration and mobility, as a function of wire diameter, and also to measure the surface state density and the surface band bending before and after the chemical treatment. We apply this method to CVD grown GaN nanowires, before and after a mild HCl etch. Using transmission electron microscope and x-ray photoelectron spectrometry we find that HCl removes the native gallium oxide. The etch is found to reduce the surface state density from 1 * 10(12) to 5.3 * 10(11) cm(2), which is calculated from a reduction of the critical radius for full depletion from 7.6 to 4 nm, and a reduction of the surface band bending from 0.53 to 0.29 eV, observed using surface photovoltage. On the average, the values of carrier concentration we obtain are about ten times smaller, and the mobility about ten times greater, than values obtained using field effect transistors. Interestingly, the weak size dependence of the mobility disappears after etching, suggesting a causal linkage between the as-grown size dependence of the mobility and the density of surface states. The proposed method provides an experimental handle to the study of surface states and their effects on the electrical properties of nanowires. PMID- 21971449 TI - Hippocampal network alterations in Alzheimer's disease and Down syndrome: from structure to therapy. AB - Hippocampal structural and functional alterations in Alzheimer's disease (AD), detected by advanced imaging methods, have been linked to significant abnormalities in multiple internal and external networks in this critical brain region. Uncovering the temporal and anatomical pattern of these network alterations would provide important clues into understanding the pathophysiology of AD and suggest new therapeutic strategies for this multi-system and prevalent disorder. Over the last decade, we have focused on studying brain structures that provide major projections to the hippocampus (HC) and the pattern of de afferentation of this area in mouse models of AD and a related neurodegenerative disorder, i.e. Down syndrome (DS). Our studies have revealed that major inputs into the hippocampal structure undergo significant age-dependent alterations. Studying locus coeruleus (LC), the sole source of noradrenergic terminals for the HC, it has been shown that these neurons show significant age-dependent degeneration in both mouse models of DS and AD. Furthermore, increasing noradrenergic signaling was able to restore cognitive function by improving synaptic plasticity, and possibly promoting microglia recruitment, and amyloid beta (Abeta) clearance in transgenic (tg) mouse models of AD. Here, we re-examine the effects of alterations in major inputs to the hippocampal region and their structural and functional consequences in mouse models of neurodegenerative disorders. We will conclude that improving the function of major hippocampal inputs could lead to a significant improvement in cognitive function in both AD and DS. PMID- 21971448 TI - Imaging the Alzheimer brain. PMID- 21971450 TI - Presence of ApoE epsilon4 allele associated with thinner frontal cortex in middle age. AB - The presence of an ApoE epsilon4 allele (epsilon4+) increases the risk of developing Alzheimer's disease (AD). Previous studies support an adverse relationship between epsilon4+ status and brain structure and function in mild cognitive impairment and AD; in contrast, the presence of an epsilon2 allele may be protective. Whether these findings reflect disease-related effects or pre existing endophenotypes, however, remains unclear. The present study examined the influence of ApoE allele status on brain structure solely during middle-age in a large, national sample. Participants were 482 men, ages 51-59, from the Vietnam Era Twin Study of Aging (VETSA). T1-weighted images were used in volumetric segmentation and cortical surface reconstruction methods to measure regional volume and thickness. Primary linear mixed effects models predicted structural measures with ApoE status (epsilon3/3, epsilon2/3, epsilon3/4) and control variables for effects of site, non-independence of twin data, age, and average cranial vault or cortical thickness. Relative to the epsilon3/3 group, the epsilon3/4 group demonstrated significantly thinner cortex in superior frontal and left rostral and right caudal midfrontal regions; there were no significant effects of epsilon4 status on any temporal lobe measures. The epsilon2/3 group demonstrated significantly thicker right parahippocampal cortex relative to the epsilon3/3 group. The ApoE epsilon4 allele may influence cortical thickness in frontal areas, which are later developing regions thought to be more susceptible to the natural aging process. Previous conflicting findings for mesial temporal regions may be driven by the inclusion of older individuals, who may evidence preclinical manifestations of disease, and by unexamined moderators of epsilon4 related effects. The presence of the epsilon2 allele was related to thicker cortex, supporting a protective role. Ongoing follow-up of the VETSA sample may shed light on the potential for age- and disease-related mediation of the influence of ApoE allele status. PMID- 21971451 TI - Survey of protocols for the manual segmentation of the hippocampus: preparatory steps towards a joint EADC-ADNI harmonized protocol. AB - Manual segmentation from magnetic resonance imaging (MR) is the gold standard for evaluating hippocampal atrophy in Alzheimer's disease (AD). Nonetheless, different segmentation protocols provide up to 2.5-fold volume differences. Here we surveyed the most frequently used segmentation protocols in the AD literature as a preliminary step for international harmonization. The anatomical landmarks (anteriormost and posteriormost slices, superior, inferior, medial, and lateral borders) were identified from 12 published protocols for hippocampal manual segmentation ([Abbreviation] first author, publication year: [B] Bartzokis, 1998; [C] Convit, 1997; [dTM] deToledo-Morrell, 2004; [H] Haller, 1997; [J] Jack, 1994; [K] Killiany, 1993; [L] Lehericy, 1994; [M] Malykhin, 2007; [Pa] Pantel, 2000; [Pr] Pruessner, 2000; [S] Soininen, 1994; [W] Watson, 1992). The hippocampi of one healthy control and one AD patient taken from the 1.5T MR ADNI database were segmented by a single rater according to each protocol. The accuracy of the protocols' interpretation and translation into practice was checked with lead authors of protocols through individual interactive web conferences. Semantically harmonized landmarks and differences were then extracted, regarding: (a) the posteriormost slice, protocol [B] being the most restrictive, and [H, M, Pa, Pr, S] the most inclusive; (b) inclusion [C, dTM, J, L, M, Pr, W] or exclusion [B, H, K, Pa, S] of alveus/fimbria; (c) separation from the parahippocampal gyrus, [C] being the most restrictive, [B, dTM, H, J, Pa, S] the most inclusive. There were no substantial differences in the definition of the anteriormost slice. This survey will allow us to operationalize differences among protocols into tracing units, measure their impact on the repeatability and diagnostic accuracy of manual hippocampal segmentation, and finally develop a harmonized protocol. PMID- 21971453 TI - Ultra-high field 7T MRI: a new tool for studying Alzheimer's disease. AB - Ultra-high field 7T MRI offers superior signal-to-noise and spatial resolution relative to any other noninvasive imaging technique. By revealing fine anatomical details of the living brain, 7T MRI allows neuroimaging researchers the opportunity to observe in patients disease-related structural changes previously apparent only on postmortem tissue analysis. Alzheimer's disease (AD) is a natural subject for this technology, and I review here two AD-related applications of 7T MRI: direct visualization of cortical plaques, and high resolution hippocampal imaging. I also discuss limitations of this technology as well as expected advances that are likely to establish 7T MRI as an increasingly important tool for the diagnosis and tracking of AD. PMID- 21971454 TI - Nuclear medicine diagnostic techniques in the era of pathophysiology-based CSF biomarkers for Alzheimer's disease. AB - Nuclear medicine techniques were the first functional imaging techniques used to support the clinical diagnosis of Alzheimer's Disease (AD). Perfusion-SPECT allows registration of regional cerebral blood flow (rCBF) which is altered in a characteristic temporal-parietal pattern in AD. Numerous studies have shown the diagnostic value of reduced CBF and metabolic changes using perfusion-SPECT and FDG-PET in AD diagnosis as well as in differential diagnosis against frontotemporal dementia (FTD), dementia with Lewy-Bodies (DLB), and vascular cognitive disorders. This renders perfusion-SPECT an important piece of the puzzle (together with other diagnostic tests) by the clinician is often faced when making a final etiologic dementia diagnosis especially between AD and FTD. A similar diagnostic value can be expected when arterial spin labeling (ASL) MRI sequence is used, but the diagnostic value has yet to be confirmed in lager studies. Recently, more pathophysiology-based biomarkers in CSF and Amyloid-PET tracers have been developed that probably have a higher diagnostic accuracy than the more indirect rCBF changes seen in perfusion-SPECT. In the current review, we describe recent advances in AD biomarkers as well as improvements in the SPECT technique. PMID- 21971452 TI - Relationship between CSF biomarkers of Alzheimer's disease and rates of regional cortical thinning in ADNI data. AB - Previously it was reported that Alzheimer's disease (AD) patients have reduced amyloid (Abeta 1-42) and elevated total tau (t-tau) and phosphorylated tau (p-tau 181p) in the cerebro-spinal fluid (CSF), suggesting that these same measures could be used to detect early AD pathology in healthy elderly (CN) and mild cognitive impairment (MCI). In this study, we tested the hypothesis that there would be an association among rates of regional brain atrophy, the CSF biomarkers Abeta 1-42, t-tau, and p-tau 181p and ApoE epsilon4 status, and that the pattern of this association would be diagnosis specific. Our findings primarily showed that lower CSF Abeta 1-42 and higher tau concentrations were associated with increased rates of regional brain tissue loss and the patterns varied across the clinical groups. Taken together, these findings demonstrate that CSF biomarker concentrations are associated with the characteristic patterns of structural brain changes in CN and MCI that resemble to a large extent the pathology seen in AD. Therefore, the finding of faster progression of brain atrophy in the presence of lower Abeta 1-42 levels and higher p-tau levels supports the hypothesis that CSF Abeta 1-42 and tau are measures of early AD pathology. Moreover, the relationship among CSF biomarkers, ApoE epsilon4 status, and brain atrophy rates are regionally varying, supporting the view that the genetic predisposition of the brain to amyloid and tau mediated pathology is regional and disease stage specific. PMID- 21971455 TI - Amyloid-beta and glucose metabolism in Alzheimer's disease. AB - This study used PET with the amyloid-beta (Abeta) imaging agent 11 C Pittsburgh Compound-B (PIB) and the glucose metabolic tracer 18F-fluorodeoxyglucose (FDG) to map the relationship of Abeta deposition to regional glucose metabolism in Alzheimer's disease (AD). Comparison of 13 AD patients' FDG scans with 11 healthy controls confirmed a typical temporo-parietal hypometabolic pattern in AD. In contrast, PIB distribution-volume-ratios showed a distinct pattern of specific tracer retention in fronto-temporo-parietal regions and striatum in AD with peaks in left frontal cortex, precuneus, temporal cortex, striatum and right posterior cingulate. There were no region-to-region or within region correlations between FDG and PIB uptake in PIB positive AD patients but when the impact of Abeta load on glucose metabolism was assessed via probabilistic maps, increased amyloid burden was coupled with decreased metabolism in temporo-parietal regions and the posterior cingulate. However, importantly, severe Abeta burden was not associated with comparable metabolic decreases in large parts of the frontal lobes, the striatum and the thalamus. PMID- 21971456 TI - Florbetaben to trace amyloid-beta in the Alzheimer brain by means of PET. AB - PET imaging of amyloid-beta has recently emerged as a valuable biomarker to support the in vivo diagnosis of Alzheimer's disease (AD). So far, however, no tracer is available suitable for general clinical routine application. Florbetaben is a promising 18F-labeled amyloid-beta-targeted PET tracer currently in Phase 2/3 clinical development. This review provides an overview on the current knowledge and future research activities on florbetaben. Recently, the first worldwide multi-center trial to test the diagnostic performance of amyloid beta PET in AD was conducted with this tracer. From this trial, a sensitivity and specificity of 80 and 91% in the discrimination between patients with probable AD and age-matched healthy controls was reported. Ongoing florbetaben PET trials deal with correlating the in vivo PET signal to post mortem histopathology evaluation, and with investigating the value of the tracer to predict progression to AD at the stage of mild cognitive impairment. The preclinical and clinical data currently available verify florbetaben as a safe and efficacious PET tracer suitable for detection of amyloid-beta deposition in the brain. The results of the ongoing trials will contribute to current knowledge on the characteristics of florbetaben, and will help to determine the future potential of florbetaben PET imaging as a visual adjunct to supplement the routine clinical "AD diagnostic toolbox". PMID- 21971458 TI - The merits of FDDNP-PET imaging in Alzheimer's disease. AB - 2-(1-{6-[(2-[fluorine-18]fluoroethyl)(methyl)amino]-2-naphthyl} ethylidene)malononitrile (FDDNP) is the first positron emission tomography (PET) molecular imaging probe to visualize Alzheimer's disease (AD) pathology in living humans. The most unique features of FDDNP are that (1) it is the only currently available radiotracer to image neurofibrillary tangles, beside amyloid aggregates, in living humans; and (2) it is also the only radiotracer to visualize AD pathology in the hippocampal region of living humans. In this article, we discuss FDDNP's unique ability to image tau pathology in living humans. Emphasizing tau pathology imaging capability using FDDNP in AD, as well as other tauopathies, is timely and beneficial considering that (1) post mortem histopathological studies using human specimens have consistently demonstrated that neurofibrillary tangles, compared with amyloid plaques, are better correlated with the disease severity and neuronal death; and (2) recently reported clinical trial failures of disease-modifying drugs in development, based on the amyloid-cascade hypothesis, suggest that some of the basic assumptions of AD causality warrant reassessment and redirection. PMID- 21971457 TI - Effects of hypoperfusion in Alzheimer's disease. AB - The role of hypoperfusion in Alzheimer's disease (AD) is a vital component to understanding the pathogenesis of this disease. Disrupted perfusion is not only evident throughout disease manifestation, it is also demonstrated during the pre clinical phase of AD (i.e., mild cognitive impairment) as well as in cognitively healthy persons at high-risk for developing AD due to family history or genetic factors. Studies have used a variety of imaging modalities (e.g., SPECT, MRI, PET) to investigate AD, but with its recent technological advancements and non invasive use of blood water as an endogenous tracer, arterial spin labeling (ASL) MRI has become an imaging technique of growing popularity. Through numerous ASL studies, it is now known that AD is associated with both global and regional cerebral hypoperfusion and that there is considerable overlap between the regions implicated in the disease state (consistently reported in precuneus/posterior cingulate and lateral parietal cortex) and those implicated in disease risk. Debate exists as to whether decreased blood flow in AD is a cause or consequence of the disease. Nonetheless, hypoperfusion in AD is associated with both structural and functional changes in the brain and offers a promising putative biomarker that could potentially identify AD in its pre-clinical state and be used to explore treatments to prevent, or at least slow, the progression of the disease. Finally, given that perfusion is a vascular phenomenon, we provide insights from a vascular lesion model (i.e., stroke) and illustrate the influence of disrupted perfusion on brain structure and function and, ultimately, cognition in AD. PMID- 21971459 TI - Research towards tau imaging. AB - Tau-bearing neurofibrillary lesions present a promising biomarker for premortem diagnosis and staging of Alzheimer's disease and certain forms of frontotemporal lobar degeneration by whole brain imaging methods. Although brain penetrating compounds capable of binding tau aggregates with high affinity have been disclosed for this purpose, the major barrier to progress remains the need for tau lesion binding selectivity relative to amyloid-beta plaques and other deposits of proteins in cross-beta-sheet conformation. Here we discuss challenges faced in the development of tau lesion-selective imaging agents, and recent preclinical advances in pursuit of this goal. PMID- 21971460 TI - Disease tracking markers for Alzheimer's disease at the prodromal (MCI) stage. AB - Older persons with Mild Cognitive Impairment (MCI) feature neurobiological Alzheimer's Disease (AD) in 50% to 70% of the cases and develop dementia within the next 5 to 7 years. Current evidence suggests that biochemical, neuroimaging, electrophysiological, and neuropsychological markers can track the disease over time since the MCI stage (also called prodromal AD). The amount of evidence supporting their validity is of variable strength. We have reviewed the current literature and categorized evidence of validity into three classes: Class A, availability of multiple serial studies; Class B a single serial study or multiple cross sectional studies of patients with increasing disease severity from MCI to probable AD; and class C, multiple cross sectional studies of patients in the dementia stage, not including the MCI stage. Several Class A studies suggest that episodic memory and semantic fluency are the most reliable neuropsychological markers of progression. Hippocampal atrophy, ventricular volume and whole brain atrophy are structural MRI markers with class A evidence. Resting-state fMRI and connectivity, and diffusion MR markers in the medial temporal white matter (parahippocampus and posterior cingulum) and hippocampus are promising but require further validation. Change in amyloid load in MCI patients warrant further investigations, e.g. over longer period of time, to assess its value as marker of disease progression. Several spectral markers of resting state EEG rhythms that might reflect neurodegenerative processes in the prodromal stage of AD (EEG power density, functional coupling, spectral coherence, and synchronization) suffer from lack of appropriately designed studies. Although serial studies on late event-related potentials (ERPs) in healthy elders or MCI patients are inconclusive, others tracking disease progression and effects of cholinesterase inhibiting drugs in AD, and cross sectional including MCI or predicting development of AD offer preliminary evidence of validity as a marker of disease progression from the MCI stage. CSF Markers, such as Abeta 1-42, t-tau and p-tau are valuable markers which support the clinical diagnosis of Alzheimer's disease. However, these markers are not sensitive to disease progression and cannot be used to monitor the severity of Alzheimer's disease. For Isoprostane F2 some evidence exists that its increase correlates with the progression and the severity of AD. PMID- 21971461 TI - Resting state cortical rhythms in mild cognitive impairment and Alzheimer's disease: electroencephalographic evidence. AB - Physiological brain aging is characterized by a combination of synaptic pruning, loss of cortico-cortical connections and neuronal apoptosis that provoke age dependent decline of cognitive functions. Neural/synaptic redundancy and plastic remodeling of brain networking, also secondary to mental and physical training, promotes maintenance of brain activity in healthy elderly for everyday life and fully productive affective and intellectual capabilities. Unfortunately, in pathological situations, aging triggers neurodegenerative processes that impact on cognition, like Alzheimer's disease (AD). Oscillatory electromagnetic brain activity is a hallmark of neuronal network function in various brain regions. Modern neurophysiological techniques including digital electroencephalography (EEG) allow non-invasive analysis of cortico-cortical connectivity and neuronal synchronization of firing, and coherence of brain rhythmic oscillations at various frequencies. The present review of field EEG literature suggests that discrimination between physiological and pathological brain aging clearly emerges at the group level, with some promising result on the informative value of EEG markers at the individual level. Integrated approaches utilizing neurophysiological techniques together with biological markers and structural and functional imaging are promising for large-scale, low-cost, widely available on the territory and non-invasive screening of at-risk populations. PMID- 21971463 TI - P300 energy loss in aging and Alzheimer's disease. AB - The amplitude of the event-related potential P300 component is sensitive to aging and Alzheimer's disease (AD). Using a standard 20-electrode configuration, the P300 was measured during an "oddball" task in 14 young normal individuals (YN: 21 41 years), 11 elderly normal individuals (EN: 61-80 years), and 23 probable AD patients (AD: 63-93 years; NINCDS-ADRDA criteria). P300 latencies and amplitudes were measured at PZ. Additionally, algorithmic calculations were made from spline plots across the 11 central electrodes for P300 peak voltage latency and total field energy. The measured versus calculated latencies were in general agreement. Furthermore, the measured P300 voltage amplitude was closely related to the calculated total field energy. P300 voltage latency was significantly prolonged in the elderly, but not more so in AD patients (average latency [ms +/- SD]; YN, 315 +/- 21; EN, 364 +/- 48 and AD, 361 +/- 56). P300 amplitude showed the expected pattern of change from young to elderly to AD (average voltage [uV +/- SD]; YN, 13 +/- 5.1; EN, 8.3 +/- 2.8; and AD, 4.9 +/- 3.3). Summing the squares of each wave (an indication of power: P = V2 R) showed the expected change with age more strongly than the P300 amplitude (average +/- SD; YN, 44,397 +/- 32,386; EN, 9,996 +/- 7,018; and AD, 3,347 +/- 2,971). Mini-Mental State Exam scores showed no relationship to P300 latency and minimal relationship to amplitude. Results suggest that the P300 is not obliterated in early AD, but is barely discernable in late AD. The approaches to calculating the P300 described here are potentially useful for measuring specific neural systems affected by aging and AD. PMID- 21971462 TI - Cognitive event-related potentials: biomarkers of synaptic dysfunction across the stages of Alzheimer's disease. AB - Cognitive event-related brain potential (ERP) studies of decision-making and attention, language, and memory impairments in Alzheimer's disease (AD) and mild cognitive impairment (MCI) are reviewed. Circumscribed lesions of the medial temporal lobe (MTL), as may be the case in individuals with amnestic MCI, generally produce altered plasticity of the late positive P600 component, with relative sparing of earlier sensory ERP components. However, as the neuropathology of AD extends to neocortical association areas, abnormalities of the P300 and N400 (and perhaps even P50) become more common. Critically, ERP studies of individuals at risk for AD may reveal neurophysiological changes prior to clinical deficits, which could advance the early detection and diagnosis of "presymptomatic AD". PMID- 21971464 TI - Evaluation and tracking of Alzheimer's disease severity using resting-state magnetoencephalography. AB - We have conducted multicenter clinical studies in which brain function was evaluated with brief, resting-state magnetoencephalography (MEG) scans. A study cohort of 117 AD patients and 123 elderly cognitively normal volunteers was recruited from community neurology clinics in Denver, Colorado and Minneapolis, Minnesota. Each subject was evaluated through neurological examination, medical history, and a modest battery of standard neuropsychological tests. Brain function was measured by a one-minute, resting-state, eyes-open MEG scan. Cross sectional analysis of MEG scans revealed global changes in the distribution of relative spectral power (centroid frequency of healthy subjects = 8.24 +/- 0.2 Hz and AD patients = 6.78 +/- 0.25 Hz) indicative of generalized slowing of brain signaling. Functional connectivity patterns were measured using the synchronous neural interactions (SNI) test, which showed a global increase in the strength of functional connectivity (cO2 value of healthy subjects = 0.059 +/- 0.0007 versus AD patients = 0.066 +/- 0.001) associated with AD. The largest magnitude disease associated changes were localized to sensors near posterior and lateral cortical regions. Part of the cohort (31 AD and 46 cognitively normal) was evaluated in an identical fashion approximately 10 months after the first assessments. Follow-up scans revealed multiple MEG scan features that correlated significantly with changes in neuropsychological test scores. Linear combinations of these MEG scan features generated an accurate multivariate model of disease progression over 10 months. Our results demonstrate the utility of brief resting-state tests based on MEG. The non-invasive, rapid and convenient nature of these scans offers a new tool for translational AD research and early phase development of novel treatments for AD. PMID- 21971465 TI - Diffusion tensor imaging of the hippocampus in MCI and early Alzheimer's disease. AB - The hippocampus is among the first brain structures to be affected by Alzheimer's disease (AD) pathology. Microstructural alterations within this region have been quantified in vivo using diffusion tensor imaging (DTI), a relatively novel MRI based technique for mapping diffusion properties of water. Existing evidence indicates that DTI-derived mean diffusivity (MD) of the anterior hippocampus is more predictive than ordinary volumetric indices of the degree of episodic memory impairment in patients with early AD. Thus, altered MD of the (anterior) hippocampus might be highly indicative of hippocampal dysfunction, thereby potentially qualifying this measure as a candidate marker for monitoring progression of AD. Longitudinal studies are needed to confirm this concept. DTI based assessment of hippocampal microstructure might be also of value for early AD diagnosis and for predicting the course of cognitive decline in subjects at risk for Alzheimer's dementia. Mean diffusivity as microstructural and volume as macrostructural index of hippocampal integrity seem to reflect different, albeit overlapping, aspects of the neurodegenerative process. In contrast, fractional anisotropy is less efficient for quantifying microstructural integrity of the diseased hippocampus in the clinical context. Development of automatic algorithms, providing MD measurements of the hippocampus for routine use, is a task for future studies. PMID- 21971466 TI - Mapping the structural brain changes in Alzheimer's disease: the independent contribution of two imaging modalities. AB - The macrostructural atrophy of Alzheimer's disease (AD) has been fully described. Current literature reports that also microstructural alterations occur in AD since the early stages. However, whether the microstructural changes offer unique information independent from macrostructural atrophy is unclear. Aim of this study is to define the independent contribution of macrostructural atrophy and microstructural alterations on AD pathology. The study involved 17 moderate to severe AD patients and 13 healthy controls. All participants underwent conventional and non conventional MRI (respectively, T1-weighted and diffusion weighted MR scanning). We processed the images in order to obtain gray and white matter volumes to assess macrostructural atrophy, and fractional anisotropy and mean diffusivity to assess the microstructural damage. Analyses of covariance between patients and controls were performed to investigate microstructural tissue damage independent of macrostructural tissue loss, and vice versa, voxel by voxel. We observed microstructural differences, independent of macrostructural atrophy, between patients and controls in temporal and retrosplenial regions, as well as in thalamus, corticopontine tracts, striatum and precentral gyrus. Volumetric differences, independent of microstructural alterations, were observed mainly in the entorhinal cortex, posterior cingulum, and splenium. Measures of microstructural damage provide unique information not obtainable with volumetric mapping in regions known to be pivotal in AD as well as in others thought to be spared. This work expands the understanding of the topography of pathological changes in AD that can be captured with imaging techniques. PMID- 21971467 TI - Multiple diffusion indices reveals white matter degeneration in Alzheimer's disease and mild cognitive impairment: a tract-based spatial statistics study. AB - Alzheimer's disease (AD) is a progressive neurodegenerative disease involving the decline of memory and other cognitive functions. Mild cognitive impairment (MCI) represents a transition phase between normal aging and early AD. The degeneration patterns of the white matter across the brain in AD and MCI remain largely unclear. Here we used diffusion tensor imaging and tract-based spatial statistics (TBSS) to investigate white matter changes in multiple diffusion indices (e.g., fractional anisotropy, axial, radial and mean diffusivities) in both AD and MCI patients. Compared with the normal controls, the AD patients had reduced fractional anisotropy and increased axial, radial and mean diffusivities in widespread white matter structures, including the corpus callosum and the white matter of lateral temporal cortex, the posterior cingulate cortex/precuneus and the fronto-parietal regions. Similar white matter regions with reduced anisotropy were also found in MCI patients but with a much less extent than in AD. Between the AD and MCI groups, there were significant differences in the axial and mean diffusivities of the white matter tracts adjacent to the posterior cingulate cortex/precuneus without anisotropy changes. Taken together, our findings based upon multiple diffusion indices (FA, axial, radial and mean diffusivities) suggest distinct degeneration behaviors of the white matter in AD and MCI. PMID- 21971469 TI - Searching for novel biomarkers using high resolution diffusion tensor imaging. AB - Diffusion tensor imaging is capable of resolving large fiber bundles (e.g. the corpus callosum) and has been quite informative in understanding the overall structural connectivity of the brain. Recent data has shown that traditional resolution limitations can be exceeded in humans in vivo to submillimeter resolution. This chapter discusses these new techniques, and specific applications to small pathways such as the perforant path in the medial temporal lobe. High-resolution diffusion tensor imaging is a promising new tool that can be used to discover novel biomarkers for Alzheimer's disease and other disorders. It allows for a much more detailed investigation of brain white matter than previously possible, perhaps offering clues into the first signs of synaptic deterioration that may precede frank neuron loss. Although these methods are still in their infancy and many challenges have to be overcome before they can be used in a clinical fashion, results so far have been promising. Challenges and future directions are discussed in detail. PMID- 21971468 TI - DTI analyses and clinical applications in Alzheimer's disease. AB - DTI is one of the most effective MR tools for the investigation of the brain anatomy. In addition to the gray matter, histopathological studies indicate that white matter is also a good target for both the early diagnosis of AD and for monitoring disease progression, which motivates us to use DTI to study AD patients in vivo. There are already a large amount of studies reporting significant differences between AD patients and controls, as well as to predict progression of disease in symptomatic non-demented individuals. Application of these findings in clinical practice remains to be demonstrated. PMID- 21971470 TI - Magnetic resonance imaging and magnetic resonance spectroscopy for detection of early Alzheimer's disease. AB - Alzheimer's disease is the most common form of neurodegenerative disorder and early detection is of great importance if new therapies are to be effectively administered. We have investigated whether the discrimination between early Alzheimer's disease (AD) and elderly healthy control subjects can be improved by adding magnetic resonance spectroscopy (MRS) measures to magnetic resonance imaging (MRI) measures. In this study 30 AD patients and 36 control subjects were included. High resolution T1-weighted axial magnetic resonance images were obtained from each subject. Automated regional volume segmentation and cortical thickness measures were determined for the images. 1H MRS was acquired from the hippocampus and LCModel was used for metabolic quantification. Altogether, this yielded 58 different volumetric, cortical thickness and metabolite ratio variables which were used for multivariate analysis to distinguish between subjects with AD and Healthy controls. Combining MRI and MRS measures resulted in a sensitivity of 97% and a specificity of 94% compared to using MRI or MRS measures alone (sensitivity: 87%, 76%, specificity: 86%, 83% respectively). Adding the MRS measures to the MRI measures more than doubled the positive likelihood ratio from 6 to 17. Adding MRS measures to a multivariate analysis of MRI measures resulted in significantly better classification than using MRI measures alone. The method shows strong potential for discriminating between Alzheimer's disease and controls. PMID- 21971472 TI - MR spectroscopy for assessment of memantine treatment in mild to moderate Alzheimer dementia. AB - OBJECTIVES: Magnetic Resonance Spectroscopy (MRS) may provide a precise and reliable assessment of the extent and severity of neural tissue loss caused by various diseases. In particular, the N-Acetyl Aspartate (NAA) and Creatine (Cr) ratio has been found to be an indicator of the degree of neuronal loss in Alzheimer's disease (AD). Memantine is thought to benefit the AD brain by stabilizing the NMDA receptors on neurons in turn reducing excitotoxicity. Despite its effectiveness in treating moderate to severe AD, memantine has not had similar success in the treatment of mildly demented AD patients. The objective of this study was to test whether memantine would slow or prevent the loss of neurons in mild to moderate AD patients. METHODS: A double-blind placebo controlled study was designed to measure the effect of a year-long course of memantine in patients with a probable AD diagnosis with mild to moderate dementia. The primary outcome measure was stipulated to be change in MRS NAA/Cr ratio in inferior parietal cortex in memantine relative to the placebo treatment condition. The secondary outcome measures were changes in cognitive and function scale scores. RESULTS: This pilot study failed to demonstrate a benefit of memantine on the primary outcome measure, the inferior parietal NAA/Cr ratio, or the secondary outcome measures. CONCLUSIONS: More studies are needed to determine the effect of memantine on regions of the brain significantly affected by AD pathology. PMID- 21971471 TI - Alzheimer's Prevention Initiative: a plan to accelerate the evaluation of presymptomatic treatments. AB - There is an urgent need to find effective presymptomatic Alzheimer's disease (AD) treatments that reduce the risk of AD symptoms or prevent them completely. It currently takes too many healthy people, too much money and too many years to evaluate the range of promising presymptomatic treatments using clinical endpoints. We have used brain imaging and other measurements to track some of the earliest changes associated with the predisposition to AD. We have proposed the Alzheimer's Prevention Initiative (API) to evaluate investigational amyloid modifying treatments in healthy people who, based on their age and genetic background, are at the highest imminent risk of developing symptomatic AD using brain imaging, cerebrospinal fluid (CSF), and cognitive endpoints. In one trial, we propose to study AD-causing presenilin 1 [PS1] mutation carriers from the world's largest early-onset AD kindred in Antioquia, Colombia, close to their estimated average age at clinical onset. In another trial, we propose to study apolipoprotein E (APOE) epsilon4 homozygotes (and possibly heterozygotes) close to their estimated average age at clinical onset. The API has several goals: 1) to evaluate investigational AD-modifying treatments sooner than otherwise possible; 2) to determine the extent to which the treatment's brain imaging and other biomarker effects predict a clinical benefit-information needed to help qualify biomarker endpoints for use in pivotal prevention trials; 3) to provide a better test of the amyloid hypothesis than clinical trials in symptomatic patients, when these treatments may be too little too late to exert their most profound effect; 4) to establish AD prevention registries needed to support these and other presymptomatic AD trials; and 5) to give those individuals at highest imminent risk of AD symptoms access to the most promising investigational treatments in clinical trials. PMID- 21971473 TI - Effects of a 6-month cognitive intervention on brain metabolism in patients with amnestic MCI and mild Alzheimer's disease. AB - The effect of cognitive intervention on brain metabolism in AD is largely unexplored. Therefore, we aimed to investigate cognitive parameters and 18FDG PET to test for effects of a cognitive intervention in patients with aMCI or mild AD. Patients with aMCI (N = 24) or mild AD (N = 15) were randomly assigned either to cognitive intervention groups (IGs), receiving weekly sessions of group-based multicomponent cognitive intervention, or active control groups (CGs), receiving pencil-paper exercises for self-study. We obtained resting-state FDG-PET scans and neuropsychological testing at baseline and after six-months. Normalized FDG PET images were analyzed using voxel-based SPM5 approaches to determine longitudinal changes, group-by-time interactions and correlations with neuropsychological outcome parameters. Primary global cognitive outcome was determined by analyses of covariance with MMSE and ADAS-cog scores as dependent measures. Both, aMCI and AD subgroups of CGs showed widespread bilateral cortical declines in FDG uptake, while the AD subgroup of IGs showed discrete decline or rather no decline in case of the aMCI subgroup. Group by time analyses revealed strongest attenuation of metabolic decline in the aMCI subgroup of the IGs, involving left anterior temporal pole and anterior cingulate gyrus. However, correlation analyses revealed only weak non-significant associations between increased FDG uptake and improvement in primary or secondary outcome parameters. Concurrently, there was significant improvement in global cognitive status in the aMCI subgroup of the IGs. A six-month cognitive intervention imparted cognitive benefits in patients with aMCI, which were concurrent with an attenuated decline of glucose metabolism in cortical regions affected by neurodegenerative AD. PMID- 21971474 TI - Cognitive training changes hippocampal function in mild cognitive impairment: a pilot study. AB - A randomized pilot experiment examined the neural substrates of response to cognitive training in participants with mild cognitive impairment (MCI). Participants performed exercises previously demonstrated to improve verbal memory and an active control group performed other computer activities. An auditory verbal fMRI task was conducted before and after the two-month training program. Verbal memory scores improved significantly and left hippocampal activation increased significantly in the experimental group (gains in 5 of 6 participants) relative to the control group (reductions in all 6 participants). Results suggest that the hippocampus in MCI may retain sufficient neuroplasticity to benefit from cognitive training. PMID- 21971475 TI - An MRI brain atrophy and lesion index to assess the progression of structural changes in Alzheimer's disease, mild cognitive impairment, and normal aging: a follow-up study. AB - BACKGROUND: A brain atrophy and lesion index (BALI) based on high-field magnetic resonance imaging (MRI) has recently been validated to evaluate structural changes in the aging brain. The present study investigated the two-year progression of brain structural deficits in people with Alzheimer's disease (AD) and mild cognitive impairment (MCI), and in healthy control older adults (HC) using the BALI rating. METHODS: T1-weighted high-resolution anatomical imaging data using 3 Tesla MRI at baseline (AD = 39, MCI = 82, HC = 58) and at 24-months were obtained from the Alzheimer's disease Neuroimaging Initiative database. Lesions in various brain structures, including the infratentorial and basal ganglia areas, and the periventricular and deep white matter and global atrophy, were evaluated and combined into the BALI scale. RESULTS: Mean progression of brain deficits over two years was evident in all diagnostic groups (p < 0.001) and was statistically greater in MCI-AD converters than in the non-converters (p = 0.044). An increase in the BALI score was significantly associated with cognitive test scores (p = 0.008 for the Mini-Mental State Examination MMSE and p = 0.013 for the Alzheimer's Disease Assessment Scale-Cognitive Subscale ADAS-cog) in a model that adjusted for age, sex, and education. CONCLUSION: The BALI rating quantified the progression of brain deficits over two years, which is associated with cognitive decline. BALI ratings may be used to help summarize AD-associated structural variations. PMID- 21971476 TI - Power calculations for clinical trials in Alzheimer's disease. AB - The Alzheimer research community is actively pursuing novel biomarker and other biologic measures to characterize disease progression or to use as outcome measures in clinical trials. One product of these efforts has been a large literature reporting power calculations and estimates of sample size for planning future clinical trials and cohort studies with longitudinal rate of change outcome measures. Sample size estimates reported in this literature vary greatly depending on a variety of factors, including the statistical methods and model assumptions used in their calculation. We review this literature and suggest standards for reporting power calculation results. Regardless of the statistical methods used, studies consistently find that volumetric neuroimaging measures of regions of interest, such as hippocampal volume, outperform global cognitive scales traditionally used in clinical treatment trials in terms of the number of subjects required to detect a fixed percentage slowing of the rate of change observed in demented and cognitively impaired populations. However, statistical methods, model assumptions, and parameter estimates used in power calculations are often not reported in sufficient detail to be of maximum utility. We review the factors that influence sample size estimates, and discuss outstanding issues relevant to planning longitudinal studies of Alzheimer's disease. PMID- 21971477 TI - Complexity of MRI white matter hyperintensity assessments in relation to cognition in aging and dementia from the Sunnybrook Dementia Study. AB - PURPOSE: Quantification methods for white matter hyperintensities (WMH) on Magnetic Resonance Imaging are heterogeneous, deterring their application. This study compared three WMH rating scales, varying in complexity, and a volumetric method, to evaluate trade-offs between complexity and clinical utility in differentiating dementia subgroups and in correlating with cognition. METHODS: WMH were rated using the Fazekas, Age-Related White Matter Changes (ARWMC) and Scheltens scales, and segmented by computational volumetry in 108 patients with Alzheimer's Disease (AD), 23 with Mild Cognitive Impairment (MCI) and 34 normal controls (NC). Global and hippocampal atrophy, age and education, were accounted for in correlations of WMH with cognitive domains. RESULTS: Intra- and inter rater reliability were high (intraclass correlation coefficients = 0.88-0.97) across rating scales. WMH scores of all scales were highly correlated with volumes (Spearman r = 0.78-0.90, Ps < 0.001), as well as with each other (Spearman r = 0.86-0.91, Ps < 0.001). The Fazekas scale showed significant separation between AD, MCI and NC using non-parametric analysis, while the ARWMC and Scheltens' scales, and WMH volumes demonstrated significant correlations (standardized beta = -0.19 to -0.24, Ps < 0.05) with cognitive domain scores using multivariate regression analysis, controlling for age, education, global and hippocampal atrophy in patients with AD. CONCLUSIONS: This study suggests that the degree of complexity of WMH rating scales did not affect validation against WMH volumes, but did vary in validation against cognition. The simplest scale performed best in separating cognitive subgroups, but the more complex scales and quantification correlated better with cognitive measures, especially executive function. Hence the best choice of scale depends on the particular application. PMID- 21971478 TI - Principles of classification analyses in mild cognitive impairment (MCI) and Alzheimer disease. AB - The majority of advanced neuroimaging studies implement group level analyses contrasting a group of patients versus a group of controls, or two groups of patients. Such analyses may identify for example changes in grey matter in specific regions associated with a given disease. Although such group investigations provided key contributions to the understanding of the pathological process surrounding a wide range of diseases, they are of limited utility at an individual level. Recently, there is a trend towards individual classification analyses, representing a fundamental shift of the research paradigm. In contrast to group comparisons, these latter studies do not provide insights on vulnerable brain areas but may allow for an early (and ideally preclinical) identification of at risk individuals in routine clinical setting. One currently very popular method in this domain are support vector machines (SVM), yet this method is only one of many available methods in the field of individual classification analyses. The current manuscript reviews the fundamental properties and features of such individual level classification analyses in neurodegenerative diseases. PMID- 21971479 TI - Combinatorial markers of mild cognitive impairment conversion to Alzheimer's disease--cytokines and MRI measures together predict disease progression. AB - Progression of people presenting with Mild Cognitive Impairment (MCI) to dementia is not certain and it is not possible for clinicians to predict which people are most likely to convert. The inability of clinicians to predict progression limits the use of MCI as a syndrome for treatment in prevention trials and, as more people present with this syndrome in memory clinics, and as earlier diagnosis is a major goal of health services, this presents an important clinical problem. Some data suggest that CSF biomarkers and functional imaging using PET might act as markers to facilitate prediction of conversion. However, both techniques are costly and not universally available. The objective of our study was to investigate the potential added benefit of combining biomarkers that are more easily obtained in routine clinical practice to predict conversion from MCI to Alzheimer's disease. To explore this we combined automated regional analysis of structural MRI with analysis of plasma cytokines and chemokines and compared these to measures of APOE genotype and clinical assessment to assess which best predict progression. In a total of 205 people with MCI, 77 of whom subsequently converted to Alzheimer's disease, we find biochemical markers of inflammation to be better predictors of conversion than APOE genotype or clinical measures (Area under the curve (AUC) 0.65, 0.62, 0.59 respectively). In a subset of subjects who also had MRI scans the combination of serum markers of inflammation and MRI automated imaging analysis provided the best predictor of conversion (AUC 0.78). These results show that the combination of imaging and cytokine biomarkers provides an improvement in prediction of MCI to AD conversion compared to either datatype alone, APOE genotype or clinical data and an accuracy of prediction that would have clinical utility. PMID- 21971480 TI - A de novo 8q22.2-24.3 duplication in a patient with mild phenotype. AB - We report a new case of 8q interstitial duplication in a patient with dysmorphic features, umbilical hernia, cryptorchidism, short stature, congenital heart defect and mild mental retardation (MR). Chromosome analysis with high resolution QFQ bands showed 46,XY, 8q+, which was interpreted as a partial duplication of the distal long arm of chromosome 8 (q22 -> qter). This chromosomal aberration was further characterized using fluorescence in situ hybridization (FISH) analyses with multiple DNA probes and array-CGH (Comparative Genomic Hybridization) experiment which demonstrated a de novo direct duplication (8)(q22.2-q24.3). We have compared this case with other partially trisomic 8q patients reported in literature and highlighted the common clinical features in 8q22-8q24 duplication syndrome. PMID- 21971481 TI - Assessing the sensitivity of methods for estimating principal causal effects. AB - The framework of principal stratification provides a way to think about treatment effects conditional on post-randomization variables, such as level of compliance. In particular, the complier average causal effect (CACE) - the effect of the treatment for those individuals who would comply with their treatment assignment under either treatment condition - is often of substantive interest. However, estimation of the CACE is not always straightforward, with a variety of estimation procedures and underlying assumptions, but little advice to help researchers select between methods. In this article, we discuss and examine two methods that rely on very different assumptions to estimate the CACE: a maximum likelihood ('joint') method that assumes the 'exclusion restriction,' (ER) and a propensity score-based method that relies on 'principal ignorability.' We detail the assumptions underlying each approach, and assess each methods' sensitivity to both its own assumptions and those of the other method using both simulated data and a motivating example. We find that the ER-based joint approach appears somewhat less sensitive to its assumptions, and that the performance of both methods is significantly improved when there are strong predictors of compliance. Interestingly, we also find that each method performs particularly well when the assumptions of the other approach are violated. These results highlight the importance of carefully selecting an estimation procedure whose assumptions are likely to be satisfied in practice and of having strong predictors of principal stratum membership. PMID- 21971482 TI - Deficiencies in acetyl-CoA carboxylase and fatty acid synthase 1 differentially affect eggshell formation and blood meal digestion in Aedes aegypti. AB - To better understand the mechanism of de novo lipid biosynthesis in blood fed Aedes aegypti mosquitoes, we quantitated acetyl-CoA carboxylase (ACC) and fatty acid synthase 1 (FAS1) transcript levels in blood fed mosquitoes, and used RNAi methods to generate ACC and FAS1 deficient mosquitoes. Using the ketogenic amino acid (14)C-leucine as a metabolic precursor of (14)C-acetyl-CoA, we found that (14)C-triacylglycerol and (14)C-phospholipid levels were significantly reduced in both ACC and FAS1 deficient mosquitoes, confirming that ACC and FAS1 are required for de novo lipid biosynthesis after blood feeding. Surprisingly however, we also found that ACC deficient mosquitoes, but not FAS1 deficient mosquitoes, produced defective oocytes, which lacked an intact eggshell and gave rise to inviable eggs. This severe phenotype was restricted to the 1st gonotrophic cycle, suggesting that the eggshell defect was due to ACC deficiencies in the follicular epithelial cells, which are replaced after each gonotrophic cycle. Consistent with lower amounts of de novo lipid biosynthesis, both ACC and FAS1 deficient mosquitoes produced significantly fewer eggs than control mosquitoes in both the 1st and 2nd gonotrophic cycles. Lastly, FAS1 deficient mosquitoes, but not ACC deficient mosquitoes, showed delayed blood meal digestion, suggesting that a feedback control mechanism may coordinate rates of fat body lipid biosynthesis and midgut digestion during feeding. We propose that decreased ACC and FAS1 enzyme levels lead to reduced lipid biosynthesis and lower fecundity, whereas altered levels of the regulatory metabolites acetyl-CoA and malonyl-CoA account for the observed defects in eggshell formation and blood meal digestion, respectively. PMID- 21971483 TI - The incidence of thyroid function abnormalities and natural course of subclinical thyroid disorders, Tehran, I.R. Iran. AB - BACKGROUND: Despite the high prevalence of thyroid dysfunction, the epidemiology and natural course of these disorders have not been identified yet. AIM: The present survey was conducted to determine the incidence of thyroid dysfunction and natural course of subclinical thyroid disorders in an urban community of Tehran, I.R. Iran. SUBJECTS AND METHODS: Serum TSH and thyroperoxidase antibody (TPOAb) were measured at baseline and after 6.7 yr from a sample of 1999 randomly selected subjects aged>=20 yr, participants of the Tehran Lipid and Glucose Study (TLGS). Median TSH value and 2.5, 5, 95, and 97.5 TSH percentiles were determined at baseline using data obtained from 808 negative TPOAb subjects with no history of any thyroid disease or surgery, goiter, nodule, taking thyroid hormone preparations or anti-thyroid drugs. In those with abnormal TSH level, total T4 and T3 uptake were measured and free T4 index was calculated. RESULTS: Normal TSH reference range was 0.4-5.8 MUU/ml according to the 2.5 and 97.5 TSH percentiles. The incidence rates of thyroid function abnormalities in 1000 subjects per year were as follows: clinical hypothyroidism: 0.28 in women and 0.21 in men; subclinical hypothyroidism: 11.59 in women and 4.69 in men; clinical hyperthyroidism: 1.4 in women and 0.21 in men; and subclinical hyperthyroidism: 5.72 in women and 3.62 in men. A significant increase was found in the frequency of positive TPOAb in women from 15.9 to 17.7% (p=0.006). Of 8 women with subclinical hypothyroidism at baseline, 5 remained unchanged, 1 became normal, and 1 developed clinical hypothyroidism at followup. Two women with subclinical hyperthyroidism normalized at follow-up. Of 2 men with subclinical hypothyroidism at baseline, 1 remained unchanged, whereas the other progressed to clinical hypothyroidism. CONCLUSION: After a 6.7 yr follow-up significant increase in the incidence of subclinical thyroid disorders was observed in both men and women, as compared to overt thyroid dysfunction. Increase in the prevalence of TPOAb positivity was observed only in women. PMID- 21971484 TI - Assemblies of perylene diimide derivatives with melamine into luminescent hydrogels. AB - We report unique and spontaneous formation of hydrogels of perylene derivatives with melamine. The luminescent gel network is formed by H-type aggregation of the perylene core, supramolecularly cross-linked by melamine units. As a result of controlled aggregation in the extended nanofibers, strong exciton fluorescence emission is observed. PMID- 21971485 TI - Nicotine induced CpG methylation of Pax6 binding motif in StAR promoter reduces the gene expression and cortisol production. AB - Steroidogenic acute regulatory protein (StAR) mediates the rate-limiting step in the synthesis of steroid hormones, essential to fetal development. We have reported that the StAR expression in fetal adrenal is inhibited in a rat model of nicotine-induced intrauterine growth retardation (IUGR). Here using primary human fetal adrenal cortex (pHFAC) cells and a human fetal adrenal cell line NCI-H295A, we show that nicotine inhibits StAR expression and cortisol production in a dose- and time-dependent manner, and prolongs the inhibitory effect on cells proliferating over 5 passages after termination of nicotine treatment. Methylation detection within the StAR promoter region uncovers a single site CpG methylation at nt -377 that is sensitive to nicotine treatment. Nicotine-induced alterations in frequency of this point methylation correlates well with the levels of StAR expression, suggesting an important role of the single site in regulating StAR expression. Further studies using bioinformatics analysis and siRNA approach reveal that the single CpG site is part of the Pax6 binding motif (CGCCTGA) in the StAR promoter. The luciferase activity assays validate that Pax6 increases StAR gene expression by binding to the glucagon G3-like motif (CGCCTGA) and methylation of this site blocks Pax6 binding and thus suppresses StAR expression. These data identify a nicotine-sensitive CpG site at the Pax6 binding motif in the StAR promoter that may play a central role in regulating StAR expression. The results suggest an epigenetic mechanism that may explain how nicotine contributes to onset of adult diseases or disorders such as metabolic syndrome via fetal programming. PMID- 21971486 TI - Shoulder pain in cases of spinal injury: influence of the position of the wheelchair seat. AB - The objective of this study was to determine the relationship between shoulder pain and the position of the seat of a wheelchair relative to the ground and to determine the relationship between shoulder pain and structural damage. A transversal study of a patient cohort of 140 patients with grade A and B spinal cord injuries below the T1 vertebra, who were full-time users of self-propelled wheelchairs, was made. The main variables are angle of the seat of the wheelchair, nuclear magnetic resonance measurements, shoulder joint range, Spinal Cord Index Measurement scale value, Wheelchair User Shoulder Pain Index and visual analogue scale value. Of the 140 patients, 99 were males (70.7%), and 41 were females (29.3%). Of these patients, 78 (55.7%) used a wheelchair seat at a straight angle, whereas 62 (44.3%) maintained an acute angle. A total of 57 (40.7%) patients presented shoulder pain within the last 6 months, and 83 (59.3%) did not. Sixty-nine (49.3%) did not present any type of shoulder injury as determined by nuclear magnetic resonance, whereas 71 (50.7%) had pathological signs. Patients with the seat at a straight angle developed 1.86 times (P<0.01) more shoulder pain and 1.73 times (P<0.001) more structural injuries than those with seats at an acute angle. Patients with structural abnormalities suffered 6.3 fold greater shoulder pain (P<0.001) than those without abnormalities. Wheelchair seats positioned parallel to the ground may be a risk factor for pain and shoulder injury. Patients with structural injuries in their shoulders have a greater risk of shoulder pain. PMID- 21971488 TI - Greg Dunn (1979 - ) hippocampus II (c. 2010). PMID- 21971487 TI - International collaborative project to compare and monitor the nutritional composition of processed foods. AB - BACKGROUND: Chronic diseases are the leading cause of premature death and disability in the world with overnutrition a primary cause of diet-related ill health. Excess energy intake, saturated fat, sugar, and salt derived from processed foods are a major cause of disease burden. Our objective is to compare the nutritional composition of processed foods between countries, between food companies, and over time. DESIGN: Surveys of processed foods will be done in each participating country using a standardized methodology. Information on the nutrient composition for each product will be sought either through direct chemical analysis, from the product label, or from the manufacturer. Foods will be categorized into 14 groups and 45 categories for the primary analyses which will compare mean levels of nutrients at baseline and over time. Initial commitments to collaboration have been obtained from 21 countries. CONCLUSIONS: This collaborative approach to the collation and sharing of data will enable objective and transparent tracking of processed food composition around the world. The information collected will support government and food industry efforts to improve the nutrient composition of processed foods around the world. PMID- 21971489 TI - Multisession radiosurgery for optic nerve sheath meningiomas--an effective option: preliminary results of a single-center experience. AB - BACKGROUND: Traditional treatment options for optic nerve sheath meningiomas (ONSMs) include observation, surgery, and radiotherapy, but to date none of these has become the clear treatment of choice. OBJECTIVE: To evaluate the effectiveness and safety of multisession radiosurgery for ONSMs. METHODS: From May 2004 to June 2008, 21 patients with ONSMs were treated by radiosurgery using the frameless CyberKnife system. Patient age ranged from 36 to 73 years (mean, 54 years). All patients were treated using multisession radiosurgery, with 5 fractions of 5 Gy each to a total dose of 25 Gy prescribed to the 75% to 85% isodose line. Patients were evaluated for tumor growth control and visual function. RESULTS: The median pretreatment tumor volume was 2.8 mL (range, 0.3-23 mL). The mean follow-up was 30 months (range, 11-68 months). All patients tolerated treatment well, with only 1 patient in whom a mild optic neuropathy developed (which remitted after systemic steroid therapy). No other acute or late radiation-induced toxicities were observed. No patients showed ONSM progression on follow-up magnetic resonance imaging. Two patients (10%) had a partial response. No patients had worsening of visual function; visual function was stable in 65% and improved in 35% of patients. CONCLUSION: Multisession radiosurgery for ONSMs was found to be safe and effective. The preliminary results from this study, in terms of growth control, visual function improvement, and toxicity, are quite promising. Further investigations are warranted. PMID- 21971490 TI - Outcome of partial contralateral C7 nerve transfer--results of 46 patients: retraction. PMID- 21971491 TI - Unilateral posterior reversible encephalopathy syndrome with hypertensive therapy of contralateral vasospasm: case report. AB - BACKGROUND AND IMPORTANCE: Hemodynamic treatment of subarachnoid hemorrhage induced vasospasm is associated with a number of systemic and cerebral risks. However, hypertensive encephalopathy has rarely been reported in the setting of induced hypertension. Recognition of this complication is nonetheless critical because failure to lower blood pressure may lead to worsening of deficits and even permanent injury. CLINICAL PRESENTATION: This report details a case of unilateral hypertensive encephalopathy (also referred to as posterior reversible encephalopathy syndrome [PRES]) in a subarachnoid hemorrhage patient who was being treated with induced hypertension for symptomatic vasospasm affecting the contralateral hemisphere. This patient developed right hemispheric deficits associated with angiographic vasospasm of the right middle cerebral artery, which responded to induced hypertension. However, within 24 hours of raising blood pressure, the patient deteriorated with new left hemispheric deficits that paradoxically worsened when blood pressure was raised further in response. Computed tomography imaging was suspicious for evolving infarction in the left hemisphere, but on reevaluation, concern for PRES was raised. Magnetic resonance imaging confirmed left hemispheric PRES, and a dramatic neurological improvement occurred almost immediately after lowering blood pressure. Repeat CT showed resolution of the left hemispheric edema. CONCLUSION: This is the first reported case of unilateral PRES in the setting of subarachnoid hemorrhage. It likely occurred because right-sided vasospasm attenuated ipsilateral distal perfusion pressures, leaving the left hemisphere vulnerable to the consequences of induced hypertension. Hypertensive encephalopathy should be considered in patients with unilateral or asymmetric vasospasm when neurological worsening occurs in the contralateral hemisphere during induced hypertension and/or the patient paradoxically worsens despite raising blood pressure. PMID- 21971493 TI - Are traumatic rectroclival hematomas located epidurally, interdurally, or subdurally? PMID- 21971495 TI - Keyhole concept in aneurysm surgery. PMID- 21971499 TI - Spectroscopic and electrochemical sensing of lanthanides with pi-extended chromophores incorporating ferrocenes and a coordinative end. AB - In this study, we report the synthesis and characterization of three novel "push pull" chromophores, in which multiple phenylenevinylene units are endcapped by ferrocene as donor units and malonate moieties as acceptor units. These chromophores have spectroscopic and electrochemical characteristics which consistently change according to the extension of the conjugated bridge, thus to the variation of the HOMO-LUMO band gap. The 1,3-dicarbonyl units, directly incorporated into the conjugated molecular structures, are able to coordinate Lewis acid-like cations, such as lanthanides, as confirmed by UV/Vis, (1)H NMR and cyclic voltammetry studies. The UV/Vis spectroscopic response upon complexation with Sc(3+) or Eu(3+) as the triflate salts is rather unselective and nonlinear in going from the least to the most pi-extended chromophore. Binding studies in MeCN, analyzed via equilibrium-restricted factor analysis, give values between log K(a) = 1.21 and 3.07 and affirm a 1 : 1 stoichiometry of the host:guest complexes in all cases. On the other hand, cyclic voltammetry reveals a selectivity in the response to Sc(3+) coordination over Ln(3+) (Eu(3+), but also Lu(3+) and Er(3+) were tested) for the two shorter chromophores, whereas the ligand with the longest pi-bridge is able to sense Er(3+) (DeltaE(1/2) complexed/uncomplexed chromophore = 20 mV) selectively over the other lanthanides. PMID- 21971501 TI - Gene expression and phosphoprotein profile of certain key neuronal signaling proteins following soman intoxication. AB - Nerve agents irreversibly inhibit acetylcholinesterase (AChE), leading to cholinergic crisis and death at acute exposure levels. The complexity, delayed onset, and persistent nature of nerve agent induced CNS effects need to be elucidated to block their multiple effects. In the present study gene expression and phosphoprotein profile of certain key neuronal proteins were studied after soman exposure. Quantitative real time PCR analysis of c-Fos, Bax, CREB and caspase 3 genes in the hippocampus, cortex and cerebellum showed that only c-Fos and Bax mRNA expression was increased significantly. Western blot analysis also confirmed the induction of c-Fos at early time points both at 0.5 and 1.0 LD(50) dose of soman exposure. Acute soman exposure caused perturbations in the phosphorylation status of ERK, JNK, p38 MAPK, CREB, c-Jun and NF-kappaB in all the three brain regions. The primary target for soman toxicity, AChE was inhibited in blood and brain up to 90%. Therapeutic treatment comprising of HI-6, atropine and diazepam has completely protected animals from death and reactivated soman inhibited AChE up to 40% in the plasma and RBC. This therapeutic regime also reduced soman induced Bax expression to near control levels, but could not reverse the soman induced changes in c-Fos expression and phosphorylation levels completely. Results suggest that exposure to soman caused persistent changes in these key brain proteins, which could lead to the development of complex neurotoxic effects and there is an urgent need for development of better drugs to stop multiple effects of nerve agents poisoning. PMID- 21971502 TI - Dose-dependent behavioral disturbances after a single neonatal Bisphenol A dose. AB - Bisphenol A is widely used in polymer products for food and beverage packaging, baby bottles, dental sealants, and fillings, adhesives, protective coatings, flame retardants, water supply pipes, and compact discs, and is found in the environment and in placental tissue, fetuses and breast milk. We have recently reported that neonatal exposure to other environmental pollutants can induce persistent aberrations in spontaneous behavior and also affect learning and memory functions in the adult animal. Furthermore, recent reports indicate that pre- and perinatal exposure to Bisphenol A can induce neurotoxic effects. The present study indicates that a single exposure to Bisphenol A on postnatal day 10 can alter adult spontaneous behavior and cognitive function in mice, effects that are both dose-response related and long-lasting/irreversible. Earlier studies on neonatal exposure to persistent organic pollutants (POPs) have shown the cholinergic system to be a target of neurotoxicity, but here only minor effects on the nicotine-induced behavior was seen. Furthermore, Morris swim-maze and the elevated plus-maze did not reveal any effects on spatial learning and anxiety like behaviors. The present findings show similarities with effects earlier reported after pre- and perinatal exposure to Bisphenol A, and also with effects seen after a single postnatal exposure to other POPs, such as PBDEs, PCBs and PFCs. PMID- 21971503 TI - Reprogramming within hours following nuclear transfer into mouse but not human zygotes. AB - Fertilized mouse zygotes can reprogram somatic cells to a pluripotent state. Human zygotes might therefore be useful for producing patient-derived pluripotent stem cells. However, logistical, legal and social considerations have limited the availability of human eggs for research. Here we show that a significant number of normal fertilized eggs (zygotes) can be obtained for reprogramming studies. Using these zygotes, we found that when the zygotic genome was replaced with that of a somatic cell, development progressed normally throughout the cleavage stages, but then arrested before the morula stage. This arrest was associated with a failure to activate transcription in the transferred somatic genome. In contrast to human zygotes, mouse zygotes reprogrammed the somatic cell genome to a pluripotent state within hours after transfer. Our results suggest that there may be a previously unappreciated barrier to successful human nuclear transfer, and that future studies could focus on the requirements for genome activation. PMID- 21971504 TI - Designing attractive models via automated identification of chaotic and oscillatory dynamical regimes. AB - Chaos and oscillations continue to capture the interest of both the scientific and public domains. Yet despite the importance of these qualitative features, most attempts at constructing mathematical models of such phenomena have taken an indirect, quantitative approach, for example, by fitting models to a finite number of data points. Here we develop a qualitative inference framework that allows us to both reverse-engineer and design systems exhibiting these and other dynamical behaviours by directly specifying the desired characteristics of the underlying dynamical attractor. This change in perspective from quantitative to qualitative dynamics, provides fundamental and new insights into the properties of dynamical systems. PMID- 21971505 TI - Spin coupling and relaxation inside molecule-metal contacts. AB - Advances in molecular electronics depend on the ability to control the charge and spin of single molecules at the interface with a metal. Here we show that bonding of metal-organic complexes to a metallic substrate induces the formation of coupled metal-ligand spin states, increasing the spin degeneracy of the molecules and opening multiple spin relaxation channels. Scanning tunnelling spectroscopy reveals the sign and magnitude of intramolecular exchange coupling as well as the orbital character of the spin-polarized molecular states. We observe coexisting Kondo, spin, and vibrational inelastic channels in a single molecule, which lead to pronounced intramolecular variations of the conductance and spin dynamics. The spin degeneracy of the molecules can be controlled by artificially fabricating molecular clusters of different size and shape. By comparing data for vibronic and spin-exchange excitations, we provide a positive test of the universal scaling properties of inelastic Kondo processes having different physical origin. PMID- 21971507 TI - Intracellular protein production in Trichoderma reesei (Hypocrea jecorina) with hydrophobin fusion technology. AB - Insufficient accumulation and the lack of efficient purification methods are the two major bottlenecks hindering the recombinant production of many proteins. Alternative production schemes are urgently needed for proteins that remain challenging to express and purify with conventional techniques. We have found that hydrophobin fusions targeted to endoplasmic reticulum (ER) can enhance the expression of target proteins simultaneously providing means for straightforward purification. Here we show that hydrophobin fusion technology induces formation of large protein bodies in the filamentous fungus Trichoderma reesei. The fusion protein remained soluble in the ER-derived protein bodies. A simple and scalable aqueous two-phase system was demonstrated to purify the hydrophobin fusion protein GFP-HFBI from the complex intracellular extracts with a recovery of up to 62%. PMID- 21971506 TI - Phosphatidylinositol(4,5)bisphosphate coordinates actin-mediated mobilization and translocation of secretory vesicles to the plasma membrane of chromaffin cells. AB - Neurosecretory vesicles undergo docking and priming before Ca(2+)-dependent fusion with the plasma membrane. Although de novo synthesis of phosphatidylinositol(4,5)bisphosphate (PtdIns(4,5)P(2)) is required for exocytosis, its precise contribution is still unclear. Here we show that inhibition of the p110delta isoform of PI3-kinase by IC87114 promotes a transient increase in PtdIns(4,5)P(2), leading to a potentiation of exocytosis in chromaffin cells. We then exploit this pathway to examine the effect of a transient PtdIns(4,5)P(2) increase on neurosecretory vesicles behaviour, outside the context of a secretagogue stimulation. Our results demonstrate that a rise in PtdIns(4,5)P(2) is sufficient to promote the mobilization and recruitment of secretory vesicles to the plasma membrane via Cdc42-mediated actin reorganization. PtdIns(4,5)P(2), therefore, orchestrates the actin-based conveyance of secretory vesicles to the plasma membrane. PMID- 21971508 TI - Short review on face rejuvenation procedures: focus on preoperative antiseptic and anesthetic delivery by JetPeelTM-3 (a high pressure oxygen delivery device). AB - AIM: Nowadays there is great attention in trying to slow and reverse the facial aging process. Esthetic medicine has been primarily based on the surgical approach for many years, but now, in order to solve the problem of aging skin, there is an increasing interest into non-invasive, possibly painless, procedures that can guarantee the patient a quick recovery. In this perspective the use of chemical peeling and dermabrasion, to achieve skin rejuvenation, is growing worldwide. These techniques are also relevant to treat skin pigmentation irregularities and to remove keratoses, lentigines, acne and other skin related conditions. One of the most interesting, safe and painless devices, useful for the effective antiaging face treatment, is JetPeelTM-3. The aim of this study was to assess the device efficacy starting from a short review on face rejuvenation procedures. METHODS: The basic action mechanism of this medical device is a constant high pressure air flux delivery, including oxygen, mixed with different chemical compounds such as peeling molecules, antioxidants, vitamins and hyaluronic acid, which are mechanically forced across the skin surface. Here we report a new approach in the clinical use of JetPeelTM-3, tested in 20 adult volunteers, consisting in the addition to the standard protocol of an anesthetic, carbocaine and a sterilizing and disinfectant agent, that is chlorexidine. In fact disinfection and sterilization of the skin surface is a peculiar step for every antiaging or therapeutic procedure. The procedure has been completed with multiple hyaluronic acid injections of the skin in order to achieve face rejuvenation. The anesthetic power of the JetPeelTM-3-carbocaine protocol has been compared to the Emla cream one. RESULTS: The spontaneous pain sensation perceived by the patients in the hemiface treated with JetPeelTM-3 was significantly lower compared to the hemiface treated with Emla cream (P<0.001) showing, consequently, that JetPeelTM-3-carbocaine protocol had the best anesthetic performance either in dermal, subdermal or subcutaneous injections compared with Emla cream. CONCLUSION: JetPeelTM-3 has proved to be a good non invasive approach and its use is recommended since it induces local anesthesia in a short time. PMID- 21971509 TI - Harnessing regulatory T cells for transplant tolerance in the clinic through mTOR inhibition: myth or reality? AB - PURPOSE OF REVIEW: The inhibition of mTOR promotes immune tolerance in mouse models of transplantation, by favoring the expansion of regulatory T cells over effector T cells. However, attempts at inducing immune tolerance with the mTOR inhibitor (mTOR-I) in humans have so far failed. We herein review the immunological obstacles that need to be overcome in order to translate mTOR-I related tolerogenic properties into the clinic. RECENT FINDINGS: Our knowledge of regulatory T-cell biology has exploded over the past few years, providing clues to explain the complex impact of prolonged mTOR inhibition on the biology of regulatory T cells. Furthermore, recent data have shed light on the unexpected pro-inflammatory burst observed in some transplant recipients treated with mTOR I. We propose that the exposure of an organism to pathogens determines the immunodominant effect of mTOR-I, altering the immune system from a state of tolerance in inbred animals to a state of infection-triggered enhanced inflammation in humans. SUMMARY: Recent advances in the understanding of the pleiotropic effects of mTOR-I on the immune system are paving the way to new therapeutic avenues. Future mTOR-I-based tolerogenic protocols should counter the mTOR-I-related inflammation in order to selectively promote expansion of stable regulatory T cells. We herein envisage promising therapeutic perspectives. PMID- 21971510 TI - Control of instant blood-mediated inflammatory reaction to improve islets of Langerhans engraftment. AB - PURPOSE OF REVIEW: Transplantation of islets of Langerhans is an emerging treatment procedure for patients with severe type 1 diabetes, but despite recent progress the procedure is associated with massive tissue loss caused by an inflammatory reaction termed instant blood-mediated inflammatory reaction (IBMIR). This reaction involves activation of the complement and coagulation cascades, ultimately resulting in clot formation and infiltration of leukocytes into the islets, which leads to disruption of islet integrity and islet destruction. RECENT FINDINGS: In this review we discuss basic mechanisms underlying the IBMIR and emerging strategies for therapeutic regulation of the IBMIR. These include the use of selective inhibitors of the coagulation and complement systems, different procedures to coat the surface of the islets as well as the development of composite islet-endothelial cell grafts. SUMMARY: The IBMIR is a major cause of tissue loss in clinical islet transplantation, and most likely in other cell therapies in which cells are exposed to blood. Thus, it is an obvious target for therapeutic intervention. Due to its complexity, it is necessary to use different strategies to control the IBMIR. PMID- 21971511 TI - Our evolving understanding of late kidney allograft failure. AB - PURPOSE OF REVIEW: Dramatic improvement in short-term results after kidney transplantation has fostered a change in focus for clinical research: further improvement in patient outcomes requires better understanding of late allograft failure. RECENT FINDINGS: As recently as a decade ago, with clinicians and investigators besot by the mistaken assumption that 'rejection' was under control, most late allograft failure was attributed to calcineurin inhibitor nephrotoxicity. Application of newer laboratory-based techniques (C4d staining, solid-phase antibody assays, and molecular profiling) has resulted in a major shift in understanding late graft failure. New data from both clinic and laboratory indicate immunologic injury, perhaps potentiated by drug minimization, as the predominant cause of late allograft failure. SUMMARY: This review traces our evolving understanding of the problem and what looks to be a paradigm change that offers new promise of effective intervention to improve long-term outcomes. PMID- 21971512 TI - Transplantation of the broadly sensitized patient: what are the options? AB - PURPOSE OF REVIEW: Recipient sensitization to a wide variety of human leukocyte antigens (HLA) represents a major barrier to transplantation. We discuss the options for the challenging group of broadly sensitized kidney transplant candidates. RECENT FINDINGS: Transplantation by way of kidney-paired donation (KPD) represents a preferable way to bypass immunological barriers. Recent data suggest that KPD programs can be optimized by the use of innovative serological techniques to define unacceptable HLA antigens, inclusion of altruistic donors or altruistic balanced paired kidney exchange, and complementary recipient desensitization. It has become evident that plasmapheresis and/or intravenous immunoglobulin (IVIG)-based crossmatch conversion may not completely prevent rejection and chronic injury. However, recent evidence suggests major improvements by sophisticated serological risk stratification and new innovative treatment principles. Wait-listed broadly sensitized patients were shown to benefit from specific allocation programs, such as priority allocation of organs via the Eurotransplant acceptable mismatch program. Recent studies have suggested a benefit from IVIG/rituximab-based desensitization on the waitlist, or apheresis based protocols for rapid antibody removal immediately before transplantation. SUMMARY: A multifaceted repertoire of complementary strategies was shown to facilitate successful live and deceased donor kidney transplantation in high-risk patients. Recent promising developments can be expected to significantly improve outcomes. PMID- 21971513 TI - Targeting JAK3 in kidney transplantation: current status and future options. AB - PURPOSE OF REVIEW: This review will discuss the mechanism of action and important clinical trial data in renal transplantation for the small molecule Janus kinase (JAK) 3 inhibitor tofacitinib, formerly known as CP-690,550 and tasocitinib. RECENT FINDINGS: JAKs are cytoplasmic tyrosine kinases that participate in the signaling of a broad range of cell surface receptors, particularly members of the cytokine receptor common gamma (cgamma) chain family. JAK3 inhibition has immunosuppressive effects and treatment with tofacitinib in clinical trials has demonstrated efficacy in autoimmune disorders such as psoriasis and rheumatoid arthritis. Nonhuman primate models of renal transplantation demonstrated prolonged graft survival with tofacitinib compared with vehicle control. Renal transplant clinical trials in humans have demonstrated tofacitinib to be noninferior to cyclosporine in terms of rejection rates and graft survival. There was also a lower rate of new-onset diabetes after transplant. However, there was a trend toward more infections, including cytomegalovirus and BK virus nephritis. SUMMARY: Tofacitinib may be a promising alternative to calcineurin inhibitors. The optimal therapeutic window is still being determined. PMID- 21971514 TI - Steroid avoidance or withdrawal in kidney transplantation. AB - PURPOSE OF REVIEW: Steroid avoidance or early withdrawal in kidney transplantation is supported by recent guidelines, but late steroid withdrawal after the first posttransplant months has been recently discouraged in those guidelines. We have assessed the recent data trying to confirm whether or not these different steroid-sparing strategies are well tolerated. RECENT FINDINGS: Reversible, mild acute rejection rates are increased after steroid avoidance or withdrawal. However, steroid avoidance or early withdrawal is well tolerated in low immunological risk kidney transplant recipients receiving induction with anti IL2 receptor antibodies or thymoglobulin and a drug regimen based on calcineurin inhibitor and mycophenolate mofetil, at least during 5 years, the longest follow up reported. In addition, steroid withdrawal after 3-6 months is associated with stable graft function and survival stable up to 3 years after transplantation, the longest follow-up reported. Although clear benefits (cardiovascular and others) are obvious in some observational studies, true benefits in randomized controlled trials remain unclear. SUMMARY: Both early and late steroid withdrawals are well tolerated in selected low-risk renal allograft recipients treated with modern potent immunosuppression. More trials with carefully designed outcome measures are needed, especially with other modern combinations, including mTOR inhibitors and/or belatacept. PMID- 21971516 TI - Inference of gain and loss events from phyletic patterns using stochastic mapping and maximum parsimony--a simulation study. AB - Bacterial evolution is characterized by frequent gain and loss events of gene families. These events can be inferred from phyletic pattern data-a compact representation of gene family repertoire across multiple genomes. The maximum parsimony paradigm is a classical and prevalent approach for the detection of gene family gains and losses mapped on specific branches. We and others have previously developed probabilistic models that aim to account for the gain and loss stochastic dynamics. These models are a critical component of a methodology termed stochastic mapping, in which probabilities and expectations of gain and loss events are estimated for each branch of an underlying phylogenetic tree. In this work, we present a phyletic pattern simulator in which the gain and loss dynamics are assumed to follow a continuous-time Markov chain along the tree. Various models and options are implemented to make the simulation software useful for a large number of studies in which binary (presence/absence) data are analyzed. Using this simulation software, we compared the ability of the maximum parsimony and the stochastic mapping approaches to accurately detect gain and loss events along the tree. Our simulations cover a large array of evolutionary scenarios in terms of the propensities for gene family gains and losses and the variability of these propensities among gene families. Although in all simulation schemes, both methods obtain relatively low levels of false positive rates, stochastic mapping outperforms maximum parsimony in terms of true positive rates. We further studied the factors that influence the performance of both methods. We find, for example, that the accuracy of maximum parsimony inference is substantially reduced when the goal is to map gain and loss events along internal branches of the phylogenetic tree. Furthermore, the accuracy of stochastic mapping is reduced with smaller data sets (limited number of gene families) due to unreliable estimation of branch lengths. Our simulator and simulation results are additionally relevant for the analysis of other types of binary-coded data, such as the existence of homologues restriction sites, gaps, and introns, to name a few. Both the simulation software and the inference methodology are freely available at a user-friendly server: http://gloome.tau.ac.il/. PMID- 21971515 TI - Nitric oxide and hypoxia exacerbate alcohol-induced mitochondrial dysfunction in hepatocytes. AB - Chronic alcohol consumption results in hepatotoxicity, steatosis, hypoxia, increased expression of inducible nitric oxide synthase (iNOS) and decreased activities of mitochondrial respiratory enzymes. The impact of these changes on cellular respiration and their interaction in a cellular setting is not well understood. In the present study we tested the hypothesis that nitric oxide (NO) dependent modulation of cellular respiration and the sensitivity to hypoxic stress is increased following chronic alcohol consumption. This is important since NO has been shown to regulate mitochondrial function through its interaction with cytochrome c oxidase, although at higher concentrations, and in combination with reactive oxygen species, can result in mitochondrial dysfunction. We found that hepatocytes isolated from alcohol-fed rats had decreased mitochondrial bioenergetic reserve capacity and were more sensitive to NO-dependent inhibition of respiration under room air and hypoxic conditions. We reasoned that this would result in greater hypoxic stress in vivo, and to test this, wild-type and iNOS(-/-) mice were administered alcohol-containing diets. Chronic alcohol consumption resulted in liver hypoxia in the wild-type mice and increased levels of hypoxia-inducible factor 1 alpha in the peri-venular region of the liver lobule. These effects were attenuated in the alcohol-fed iNOS(-/-) mice suggesting that increased mitochondrial sensitivity to NO and reactive nitrogen species in hepatocytes and iNOS plays a critical role in determining the response to hypoxic stress in vivo. These data support the concept that the combined effects of NO and ethanol contribute to an increased susceptibility to hypoxia and the deleterious effects of alcohol consumption on liver. PMID- 21971517 TI - Sequencing and analysis of plastid genome in mycoheterotrophic orchid Neottia nidus-avis. AB - Plastids are the semiautonomous organelles that possess their own genome inherited from the cyanobacterial ancestor. The primary function of plastids is photosynthesis so the structure and evolution of plastid genomes are extensively studied in photosynthetic plants. In contrast, little is known about the plastomes of nonphotosynthetic species. In higher plants, plastid genome sequences are available for only three strictly nonphotosynthetic species, the liverwort Aneura mirabilis and two flowering plants, Epifagus virginiana and Rhizanthella gardneri. We report here the complete sequence of a plastid genome of nonphotosynthetic mycoheterotrophic orchid Neottia nidus-avis, determined using 454 pyrosequencing technology. It was found to be reduced in both genome size and gene content; this reduction is however not as drastic as in the other nonphotosynthetic orchid, R. gardneri. Neottia plastome lacks all genes encoding photosynthetic proteins, RNA polymerase subunits but retains most genes of translational apparatus. Those genes that are retained have an increased rate of both synonymous and nonsynonymous substitutions but do not exhibit relaxation of purifying selection either in Neottia or in Rhizanthella. PMID- 21971518 TI - Glucocorticoid receptors in human epicardial adipose tissue: role of coronary status. AB - BACKGROUND: Epicardial adipose tissue (EAT) is in close contact with coronary vessels and therefore could alter coronary homeostasis. Glucocorticoids are pathophysiological mediators of visceral fat deposition and its associated atherogenic complications. AIM: We investigated in EAT the expression of the glucocorticoid receptor (GR) and its various (A, B, C) promoters. MATERIALS AND METHODS: Paired subcutaneous adipose tissue (SAT) and EAT biopsies were obtained from 15 patients with coronary artery disease (CAD) and 12 patients without CAD (NCAD). GR and 11beta-hydroxysteroid dehydrogenase type 1 protein (11beta-HSD-1, the enzyme which converts inactive cortisone into active cortisol) were studied by immunohistochemistry and GR and its various promoters were studied by mRNA quantitative RT-PCR. RESULTS: GR and 11beta-HSD-1 protein were expressed in adipocytes, stromal areas, isolated stromal cells close to adipocytes, and blood vessels. Total GR mRNA levels did not differ in SAT obtained from NCAD or CAD patients and were decreased in EAT, irrespectively of the coronary status, with parallel changes in promoter B- and C-, but not promoter A-associated transcripts. Total GR mRNA and adipocyte surface in EAT obtained from CAD patients were correlated negatively (p<0.035, r=0.39). CONCLUSIONS: Our findings demonstrate that in EAT, GR gene promoters could play a role in tissue- specific GR expression levels. EAT may be less sensitive to glucocorticoids than SAT, preventing the EAT mass development in CAD patients and suggesting a protective role on coronary homeostasis. PMID- 21971519 TI - p38 Mitogen-activated protein kinase signaling regulates streptococcal M1 protein induced neutrophil activation and lung injury. AB - M1 serotype of Streptococcus pyogenes can cause STSS and acute lung damage. Herein, the purpose was to define the role of p38 MAPK signaling in M1 protein induced pulmonary injury. Male C57BL/6 mice were treated with specific p38 MAPK inhibitors (SB 239063 and SKF 86002) prior to M1 protein challenge. Edema, neutrophil infiltration, and CXC chemokines were determined in the lung, 4 h after M1 protein administration. Flow cytometry was used to determine Mac-1 expression. Phosphorylation and activity of p38 MAPK were determined by immunoprecipitation and Western blot. IVM was used to analyze leukocyte endothelium interactions in the pulmonary microcirculation. M1 protein challenge increased phosphorylation and activity of p38 MAPK in the lung, which was inhibited by SB 239063 and SKF 86002. Inhibition of p38 MAPK activity decreased M1 protein-induced infiltration of neutrophils, edema, and CXC chemokine formation in the lung, as well as Mac-1 up-regulation on neutrophils. IVM showed that p38 MAPK inhibition reduced leukocyte rolling and adhesion in the pulmonary microvasculature of M1 protein-treated mice. Our results indicate that p38 MAPK signaling regulates neutrophil infiltration in acute lung injury induced by streptococcal M1 protein. Moreover, p38 MAPK activity controls CXC chemokine formation in the lung, as well as neutrophil expression of Mac-1 and recruitment in the pulmonary microvasculature. In conclusion, these findings suggest that targeting the p38 MAPK signaling pathway may open new opportunities to protect against lung injury in streptococcal infections. PMID- 21971521 TI - Six new metal-organic frameworks with multi-carboxylic acids and imidazole-based spacers: syntheses, structures and properties. AB - Six new metal-organic frameworks [Cu(obba)(bimb).(obbaH(2))](n) (1), [Cu(obba)(bimb)](n) (2), [Zn(2)(obba)(2)(bimb)(2)(DMF)(2)(H(2)O)(3.5)](n) (3), [Ni(3)(2,2',4,4'-bptcH)(2)(bimb)(2)(H(2)O)(2).(H(2)O)(2)](n) (4), [Ni(2)(bimb)(3)(H(2)O)(6).(aobtc).(DMF)(2).(H(2)O)(2)](n) (5) and [Cd(3,3',4,4' bptcH(2))(H(2)O).(bimb)](n) (6), were obtained by reactions of 4,4'-bis(1 imidazolyl)biphenyl (bimb) and multi-carboxylic acids of 4,4'-oxybis(benzoic acid) (obbaH(2)), 2,2',4,4'-biphenyltetracarboxylate acid (2,2',4,4'-bptcH(4)), azoxybenzene-3,3',5,5'-tetracarboxylic acid (aobtcH(4)), and 3,3',4,4' biphenyltetracarboxylate acid (3,3',4,4'-bptcH(4)) with corresponding metal salts under hydro/solvothermal conditions, respectively. Complexes 1-3 have entangled structures with different topologies: 1 is a 3-fold interpenetrating NbO three dimensional (3D) network; 2 is a 3-fold interpenetrating dmp 3D net; 3 is a 6 fold interpenetrating dia 3D chiral net containing rare 1D helical chains with the same handedness. Complex 4 is an uninodal 6-connected network with a Schafli symbol of (4(8)6(4)8(3)) based on the trinuclear Ni(II) subunits, while complexes 5 and 6 are 1D chains. Interestingly, compound 6 represents the rare example of MOFs that exhibit high photocatalytic activity for dye degradation under visible light and shows good stability towards photocatalysis. Complexes 3 and 6 exhibit intense blue emissions in the solid state at room temperature whereas 3 appears to be a good candidate of novel hybrid inorganic-organic NLO material. PMID- 21971520 TI - Enhanced Toll-like receptor (TLR) responses of TNFR-associated factor 3 (TRAF3) deficient B lymphocytes. AB - The key role of TRAF6 in TLR signaling pathways is well known. More recent evidence has implicated TRAF3 as another TRAF family member important to certain TLR responses of myeloid cells. Previous studies demonstrate that TRAF3 functions are highly context-dependent, displaying receptor and cell-type specificity. We thus examined the TLR responses of TRAF3(-/-)mouse B lymphocytes to test the hypothesis that TRAF3 plays distinct roles in such responses, depending on cell type. TRAF3(-/-) DC are known to have a defect in type 1 IFN production and here, showed diminished production of TNF and IL-10 and unaltered IL-6. In marked contrast, TRAF3(-/-) B cells made elevated amounts of TNF and IL-6 protein, as well as IL-10 and IP-10 mRNA, in response to TLR ligands. Also, in contrast to TRAF3(-/-) DC, the type 1 IFN pathway was elevated in TRAF3(-/-) B cells. Increased early responses of TRAF3(-/-) B cells to TLR signals were independent of cell survival or proliferation but associated with elevated canonical NF kappaB activation. Additionally, TRAF3(-/-) B cells displayed enhanced TLR mediated expression of AID and Ig isotype switching. Thus, TRAF3 plays varied and cell type-specific, biological roles in TLR responses. PMID- 21971522 TI - Translational control mechanisms in metabolic regulation: critical role of RNA binding proteins, microRNAs, and cytoplasmic RNA granules. AB - Regulated cell metabolism involves acute and chronic regulation of gene expression by various nutritional and endocrine stimuli. To respond effectively to endogenous and exogenous signals, cells require rapid response mechanisms to modulate transcript expression and protein synthesis and cannot, in most cases, rely on control of transcriptional initiation that requires hours to take effect. Thus, co- and posttranslational mechanisms have been increasingly recognized as key modulators of metabolic function. This review highlights the critical role of mRNA translational control in modulation of global protein synthesis as well as specific protein factors that regulate metabolic function. First, the complex lifecycle of eukaryotic mRNAs will be reviewed, including our current understanding of translational control mechanisms, regulation by RNA binding proteins and microRNAs, and the role of RNA granules, including processing bodies and stress granules. Second, the current evidence linking regulation of mRNA translation with normal physiological and metabolic pathways and the associated disease states are reviewed. A growing body of evidence supports a key role of translational control in metabolic regulation and implicates translational mechanisms in the pathogenesis of metabolic disorders such as type 2 diabetes. The review also highlights translational control of apolipoprotein B (apoB) mRNA by insulin as a clear example of endocrine modulation of mRNA translation to bring about changes in specific metabolic pathways. Recent findings made on the role of 5'-untranslated regions (5'-UTR), 3'-UTR, RNA binding proteins, and RNA granules in mediating insulin regulation of apoB mRNA translation, apoB protein synthesis, and hepatic lipoprotein production are discussed. PMID- 21971523 TI - Older men exhibit reduced efficacy of and heightened potency downregulation by intravenous pulses of recombinant human LH: a study in 92 healthy men. AB - Direct sampling of the human spermatic veins has disclosed concomitant LH and testosterone (T) pulses, suggesting pulsatile LH concentration-dependent stimulation of T secretion. However, studies to date have examined this hypothesis using only pharmacological stimulation with hCG. The present study tests the hypothesis that age is marked by decreased T secretory responses to repeated near-physiological iv pulses of recombinant human LH administered in a Clinical Translational Science Center. Participants included 92 healthy men aged 18-75 yr with BMI 18-34 kg/m(2). The contribution of endogenous LH pulses was minimized by combined injection of a selective GnRH receptor antagonist sc and successive pulses of biosynthetic LH iv. A new analytical dose response model was applied to estimate the properties of exogenous LH's drive of T secretion. Regression of LH-T dose response potency estimates on age showed that the efficacy of pulses of biosynthetic LH progressively decreased with age (P = 0.014, r = 0.26). Testis sensitivity to exogenous LH pulses also declined with age (P = 0.011, r = 0.27). Moreover, estimated Leydig cell downregulation by LH pulses rose significantly with age (P = 0.039, r = 0.22). These outcomes were selective, since the recovery potency of infused LH was not affected by age but was reduced by increasing BMI (P = 0.011, r = 0.27). Assuming stable bioactivity of infused recombinant human LH, these novel data indicate that factors associated with age and BMI attenuate LH efficacy and testis sensitivity and augment Leydig cell downregulation in healthy men. PMID- 21971524 TI - Mesenchymal stem cell transplantation for the infarcted heart: a role in minimizing abnormalities in cardiac-specific energy metabolism. AB - Intense interest has been focused on cell-based therapy for the infarcted heart given that stem cells have exhibited the ability to reduce infarct size and mitigate cardiac dysfunction. Despite this, it is unknown whether mesenchymal stem cell (MSC) therapy can prevent metabolic remodeling following a myocardial infarction (MI). This study examines the ability of MSCs to rescue the infarcted heart from perturbed substrate uptake in vivo. C57BL/6 mice underwent chronic ligation of the left anterior descending coronary artery to induce a MI. Echocardiography was performed on conscious mice at baseline as well as 7 and 23 days post-MI. Twenty-eight days following the ligation procedure, hyperinsulinemic euglycemic clamps assessed in vivo insulin sensitivity. Isotopic tracer administration evaluated whole body, peripheral tissue, and cardiac specific glucose and fatty acid utilization. To gain insight into the mechanisms by which MSCs modulate metabolism, mitochondrial function was assessed by high resolution respirometry using permeabilized cardiac fibers. Data show that MSC transplantation preserves insulin-stimulated fatty acid uptake in the peri infarct region (4.25 +/- 0.64 vs. 2.57 +/- 0.34 vs. 3.89 +/- 0.54 MUmol.100 g( 1).min(-1), SHAM vs. MI + PBS vs. MI + MSC; P < 0.05) and prevents increases in glucose uptake in the remote left ventricle (3.11 +/- 0.43 vs. 3.81 +/- 0.79 vs. 6.36 +/- 1.08 MUmol.100 g(-1).min(-1), SHAM vs. MI + PBS vs. MI + MSC; P < 0.05). This was associated with an enhanced efficiency of mitochondrial oxidative phosphorylation with a respiratory control ratio of 3.36 +/- 0.18 in MSC-treated cardiac fibers vs. 2.57 +/- 0.14 in the infarct-only fibers (P < 0.05). In conclusion, MSC therapy exhibits the potential to rescue the heart from metabolic aberrations following a MI. Restoration of metabolic flexibility is important given the metabolic demands of the heart and the role of energetics in the progression to heart failure. PMID- 21971525 TI - Regulatory function of conserved sequences upstream of the long-wave sensitive opsin genes in teleost fishes. AB - Vertebrate opsin genes often occur in sets of tandem duplicates, and their expression varies developmentally and in response to environmental cues. We previously identified two highly conserved regions upstream of the long-wave sensitive opsin (LWS) gene cluster in teleosts. This region has since been shown in zebrafish to drive expression of LWS genes in vivo. In order to further investigate how elements in this region control opsin gene expression, we tested constructs encompassing the highly conserved regions and the less conserved portions upstream of the coding sequences in a promoter-less luciferase expression system. A ~4500 bp construct of the upstream region, including the highly-conserved regions Reg I and Reg II, increased expression 100-fold, and successive 5' deletions reduced expression relative to the full 4.5 Kb region. Gene expression was highest when the transcription factor RORalpha was co transfected with the proposed regulatory regions. Because these regions were tested in a promoter-less expression system, they include elements able to initiate and drive transcription. Teleosts exhibit complex color-mediated adaptive behavior and their adaptive significance has been well documented in several species. Therefore these upstream regions of LWS represent a model system for understanding the molecular basis of adaptive variation in gene regulation of color vision. PMID- 21971526 TI - A new precipitation pathway for calcium sulfate dihydrate (gypsum) via amorphous and hemihydrate intermediates. AB - This work investigates the early stages of precipitation of calcium sulfate from aqueous solution at room temperature and shows for the first time that amorphous calcium sulfate (ACS) and calcium sulfate hemihydrate are sequentially precipitated prior to calcium sulfate dihydrate (gypsum). PMID- 21971527 TI - Characterisation of microglia during de- and remyelination: can they create a repair promoting environment? AB - Microglia play a key role in the initiation and perpetuation of de- and remyelination because of their ability to present antigens and clear cell debris by phagocytosis. Different factors expressed or secreted by microglia seem to play an important role in regenerative processes. But it remains unclear which factors lead to a protective microglial phenotype and recent data indicate region specific differences within the central nervous system (CNS) for both de /remyelination and microglial response. In order to identify important factors that promote neuroprotection, we examined changes in microglial phenotypes in the cuprizone model. We undertook an extensive and detailed analysis of the expression of surface markers as well as cytokines, growth factors, and the phagocytosis activity of microglia. We found a pronounced increase of phagocytosis activity of microglia during demyelination associated with an upregulation of phagocytic receptors, from which TREM-2b was the most prominent. The expression of MHC II was only increased at the peak of demyelination but costimulatory molecules showed no significant changes. Interestingly, the proinflammatory cytokine TNF-alpha was upregulated while the anti-inflammatory cytokines IL-10 and TGF-beta remained unchanged. The growth factors IFG-1 and FGF 2, which were both suggested to promote remyelination, were increased during demyelination. Our findings characterise changes of microglial markers during de- and remyelination indicating that debris clearance mediated via TREM-2b plays a central role in the regulation of these processes. Microglial phagocytosis as well as production of TNF-alpha, IGF-1, and FGF-2 seems to be important factors for the creation of an environment promoting regeneration. PMID- 21971528 TI - High-fat diet exacerbates MPTP-induced dopaminergic degeneration in mice. AB - The identification of modifiable nutritional risk factors is highly relevant to the development of preventive strategies for neurodegenerative disorders including Parkinson's disease (PD). In this study, adult C57BL/6 mice were fed either a control (CD-12%kcal) or a high-fat diet (HFD-60%kcal) for 8 weeks prior to MPTP exposure, a toxin which recreates a number of pathological features of PD. HFD-fed mice significantly gained weight (+41%), developed insulin resistance and a systemic immune response characterized by an increase in circulating leukocytes and plasmatic cytokines/chemokines (interleukin-1alpha, MCP-1, MIP 1alpha). As expected, the MPTP treatment produced nigral dopaminergic degeneration as evidenced by the loss of striatal dopamine and the decreased number of nigral tyrosine hydroxylase (TH)- and dopamine transporter-expressing neurons (23% and 25%, respectively). However, exposure to HFD exacerbated the effects of MPTP on striatal TH (23%) and dopamine levels (32%), indicating that diet-induced obesity is associated with a reduced capacity of nigral dopaminergic terminals to cope with MPTP-induced neurotoxicity. Since high-fat consumption is commonplace in our modern society, dietary fat intake may represent an important modifiable risk factor for PD. PMID- 21971529 TI - Adenine-containing codons enhance protein synthesis by promoting mRNA binding to ribosomal 30S subunits provided that specific tRNAs are not exhausted. AB - Adenines downstream of the initiation codon promote protein synthesis; however, some adenine-containing codons (AGA, AGG and AUA) at early positions inhibit protein synthesis when cognate tRNA is exhausted. It has also been reported, although not convincingly, the presence of adenines enhancing mRNA binding to the ribosome. To understand these apparent inconsistencies we analyzed the effect of these codons in mRNA-ribosome binding strength, mRNA stability, the production of peptidyl-tRNA (pep-tRNA) and protein synthesis. Constructs harboring lacZ derivatives were obtained by site directed mutagenesis where tandems of GGG, AGG, AGA, ATA and AAA codons were inserted at codon positions 2-3 and 3-4. Codons containing more adenines, irrespective of being common or rare, (AAA, ATA and AGA) promoted a higher synthesis of beta-galactosidase (beta-gal) in comparison with those rich in guanines (GGG and AGG) in a wild type transcription translation system. Full-length mRNAs were also detected when the adenine-rich constructs were expressed in wild type cells. Under conditions where the pool of tRNAs is readily exhausted (pep-tRNA hydrolase defective cells), the adenine-rich lacZ derivatives caused a stronger and general inhibition of protein synthesis and cell growth. With the exception of the ATA lacZ derivative, only plasmid constructs containing hungry codons generated pep-tRNA (AGA and to a lesser extent AGG) in Pth defective cells. Codons containing more adenines clearly promoted lacZ mRNA binding to 30S subunit. The GGG lacZ mRNA showed a moderate increase in binding when mRNA secondary structures were disrupted by heating mRNAs before the binding assay which agrees with the lacZ mRNA secondary structures predicted with MFOLD. Altogether, these results indicate that mRNA binding to ribosome plays a major role in the enhancement of translation by adenine-rich codons irrespective of codon usage. This effect is naturally expressed in wild type systems and depends on adenine content, in contrast to the inhibition caused after over-expressing the lacZ derivatives containing rare codons in Pth defective cells. PMID- 21971531 TI - Time-resolved photoelectron imaging of the chloranil radical anion: ultrafast relaxation of electronically excited electron acceptor states. AB - The spectroscopy and dynamics of near-threshold excited states of the isolated chloranil radical anion are investigated using photoelectron imaging. The photoelectron images taken at 480 nm clearly indicate resonance-enhanced photodetachment via a bound electronic excited state. Time-resolved photoelectron imaging reveals that the excited state rapidly decays on a timescale of 130 fs via internal conversion. The ultrafast relaxation dynamics of excited states near threshold are pertinent to common electron acceptor molecules based on the quinone moiety and may serve as doorway states that enable efficient electron transfer in the highly exergonic inverted regime, despite the presence of large free energy barriers. PMID- 21971530 TI - Eukaryotic extracellular catalase-peroxidase from Magnaporthe grisea - Biophysical/chemical characterization of the first representative from a novel phytopathogenic KatG group. AB - All phytopathogenic fungi have two catalase-peroxidase paralogues located either intracellularly (KatG1) or extracellularly (KatG2). Here, for the first time a secreted bifunctional, homodimeric catalase-peroxidase (KatG2 from the rice blast fungus Magnaporthe grisea) has been produced heterologously with almost 100% heme occupancy and comprehensively investigated by using a broad set of methods including UV-Vis, ECD and resonance Raman spectroscopy (RR), thin-layer spectroelectrochemistry, mass spectrometry, steady-state & presteady-state spectroscopy. RR spectroscopy reveals that MagKatG2 shows a unique mixed-spin state, non-planar heme b, and a proximal histidine with pronounced imidazolate character. At pH 7.0 and 25 degrees C, the standard reduction potential E degrees ' of the Fe(III)/Fe(II) couple for the high-spin native protein was found to fall in the range typical for the KatG family. Binding of cyanide was relatively slow at pH 7.0 and 25 degrees C and with a K(d) value significantly higher than for the intracellular counterpart. Demonstrated by mass spectrometry MagKatG2 has the typical Trp118-Tyr251-Met277 adduct that is essential for its predominantly catalase activity at the unique acidic pH optimum. In addition, MagKatG2 acts as a versatile peroxidase using both one- and two-electron donors. Based on these data, structure-function relationships of extracellular eukaryotic KatGs are discussed with respect to intracellular KatGs and possible role(s) in host-pathogen interaction. PMID- 21971532 TI - Efficacy and tolerability of venlafaxine versus specific serotonin reuptake inhibitors in treatment of major depressive disorder: a meta-analysis of published studies. AB - Specific serotonin reuptake inhibitors (SSRIs) are considered as first-line treatment in major depressive disorder (MDD). There is evidence that venlafaxine may be more effective than several antidepressants in the treatment of MDD. This meta-analysis includes all published, randomized, double-blind, head-to-head trials, which compared venlafaxine and an SSRI in the treatment of MDD in adults. Twenty-six trials comparing venlafaxine with an SSRI were included (total participants: 5858). Meta-analysis using a random effect model showed that venlafaxine was superior to SSRIs in achieving remission [odds ratio (OR)=1.13, 95% confidence interval (CI)=1.0-1.28, P=0.05] and response (OR=1.17, 95% CI=1.03 1.34, P=0.02). Subgroup analysis found that venlafaxine had a significantly better response rate than fluoxetine (OR=1.28, 95% CI=1.05-1.55, P=0.01). There were no significant differences in response or remission between venlafaxine and other individual SSRIs. There was no significant difference in all cause discontinuation between venlafaxine and SSRIs (OR=1.10, 95% CI=0.97-1.25, P=0.15). Venlafaxine had significantly higher discontinuation due to adverse events compared with SSRIs (OR=1.41, 95% CI=1.10-1.79, P=0.006). The superior efficacy of venlafaxine over SSRIs is of clinical importance. However, higher rates of discontinuation due to adverse events for venlafaxine compared with SSRIs are a disadvantage. Findings of this meta-analysis that included only published studies were similar to those from meta-analysis that included unpublished data. PMID- 21971533 TI - Assessing the relationship between functional impairment/recovery and depression severity: a pooled analysis. AB - The objective of this study was to explore the relationship between assessments of functional impairment, emotional well-being, and depression symptoms. Data were pooled from 3530 outpatients with major depressive disorder enrolled in 10 desvenlafaxine clinical trials. The primary outcome measures included (a) the 17 item Hamilton Rating Scale for Depression (HAM-D17) as a measure of depressive symptom severity and (b) the Sheehan Disability Scale (SDS) and five-item World Health Organization Well-Being Index (WHO-5) as measures of functional impairment and well-being. A linear regression model was used to identify the SDS and WHO-5 values that equate to the predetermined clinically relevant three-point difference between active treatment and placebo on the HAM-D17. A receiver operating characteristic analysis was conducted to determine the SDS score that equates to a remission of depression symptoms (i.e. HAM-D17<=7). An approximate three-point difference between active treatment and placebo on the SDS (2.8) and WHO-5 (2.5) was determined to be clinically relevant in relation to improvements in depressive symptoms. An SDS of less than or equal to 7 was equivalent to a remission of depression symptoms, providing a definition of functional remission. A better understanding of the relationship between depressive symptoms and functional impairment and well-being may provide clinicians with a more comprehensive means of assessing treatment effects in major depressive disorder. PMID- 21971535 TI - Effects of gut-directed hypnotherapy on IBS in different clinical settings results from two randomized, controlled trials. AB - OBJECTIVES: Gut-directed hypnotherapy has been found to be effective in irritable bowel syndrome (IBS). However, randomized, controlled studies are rare and few have been performed outside highly specialized research centers. The objective of this study was to study the effect of gut-directed hypnotherapy in IBS in different clinical settings outside the traditional research units. METHODS: The study population included IBS patients refractory to standard management. In study 1, patients were randomized to receive gut-directed hypnotherapy (12 sessions, 1 h/week) in psychology private practices or supportive therapy, whereas patients were randomized to receive gut-directed hypnotherapy in a small county hospital or to serve as waiting list controls in study 2. Gastrointestinal symptom severity and quality of life were evaluated at baseline, at 3 months follow-up and after 1 year. RESULTS: We randomized 138 IBS patients refractory to standard management, 90 in study 1 and 48 in study 2. In both the studies, IBS related symptoms were improved at 3 months in the gut-directed hypnotherapy groups (P<0.05), but not in the control groups (ns). In study 1, a significantly greater improvement of IBS-related symptom severity could be detected in the gut directed hypnotherapy group than in the control group (P<0.05), and a trend in the same direction was seen in study 2 (P=0.17). The results seen at 3 months were sustained up to 1 year. CONCLUSIONS: Gut-directed hypnotherapy is an effective treatment alternative for patients with refractory IBS, but the effectiveness is lower when the therapy is given outside the highly specialized research centers. PMID- 21971536 TI - Comparison of transient elastography and acoustic radiation force impulse for non invasive staging of liver fibrosis in patients with chronic hepatitis C. AB - OBJECTIVES: Transient elastography (TE) is adequate for a diagnosis of cirrhosis, but its accuracy for milder stages of fibrosis is much less satisfactory. The objective of this study was to compare the performance and the discordance rate of acoustic radiation force impulse (ARFI) and TE with liver biopsy in a cohort of chronic hepatitis C (CHC) patients. METHODS: One hundred thirty-nine consecutive patients with CHC were enrolled in two tertiary centers, and evaluated for histological (Metavir score) and biochemical features. All patients underwent TE and ARFI. RESULTS: TE was unreliable in nine patients (6.5%), while in no cases (0%) were ARFI invalid measurements recorded (P=0.029). By area under receiver operating characteristic curve (AUROC), the best cutoff values for TE and ARFI for significant fibrosis (>=F2) were >=6.5 kPa (AUROC: 0.78) and >=1.3 m/s (AUROC: 0.86), respectively. For severe fibrosis (F3-F4), these cutoff values were 8.8 kPa (AUROC: 0.83) for TE and 1.7 m/s (AUROC: 0.94) for ARFI. For cirrhosis, TE had its best cutoff at >=11 kPa (AUROC: 0.80) and ARFI at >=2.0 m/s (AUROC: 0.89). By pairwise comparison of AUROC, ARFI was significantly more accurate than TE for a diagnosis of significant and severe fibrosis (P=0.024 and P=0.002, respectively), while this difference was only marginal for cirrhosis (P=0.09). By partial AUROC analysis, ARFI performance results significantly higher for all three stages of fibrosis. The average concordance rates of TE and ARFI vs. liver biopsy were 45.4 and 54.7%, respectively. By multivariate analysis, ARFI was not associated with alanine aminotransferase (ALT), body mass index, Metavir grade, and liver steatosis, while TE was significantly correlated with the ALT value (P=0.027). CONCLUSIONS: In a cohort of patients with CHC, ARFI imaging was more accurate than TE for the non-invasive staging of both significant and severe classes of liver fibrosis. PMID- 21971537 TI - Clinical factors associated with non-polypoid colonic adenomas >=6 mm: a prospective study in an asymptomatic population using a high-definition colonoscope. AB - OBJECTIVES: To examine the clinical factors associated with adenomas >=6 mm presenting as non-polypoid polyps. METHODS: We conducted a prospective cross sectional examination with a target population of consecutive asymptomatic patients presenting to a University endoscopy center for screening colonoscopy. Data, which included demographics, known colorectal cancer risk factors, and medications, were collected. One endoscopist using a high-definition wide-angle colonoscope performed all of the colonoscopies. Polyp morphology was classified according to the JRSC (Japanese Research Society for Cancer of Colon and Rectum) JRSC guidelines. RESULTS: A total of 600 patients were screened and 150 adenomas >=6 mm were detected. Of these 150 adenomas, 70 adenomas had a non-polypoid morphology while 80 were polypoid. Adenomas were more likely to present as non polypoid in women as compared with men (adjusted odds ratio (AOR)=2.49; 95% confidence interval (CI)=1.08-5.75, P=0.03). Location of the adenoma in the proximal colon (AOR=4.21; 95% CI=1.83-9.71, P=0.001) and smoking (AOR=2.54; 95% CI=1.01-6.38, P=0.048) were independent predictors of flat morphology. In addition, advanced adenomas were also more likely to be flat in women (AOR=7.99; 95% CI=1.32-48.39, P=0.02) and proximal location was an independent predictor of flat morphology. CONCLUSIONS: Adenomas >=6 mm and advanced lesions were more likely to present as non-polypoid polyps in women when compared with men. Proximal location and smoking were also observed to be independent predictors of flat morphology. PMID- 21971539 TI - Azilsartan medoxomil for the treatment of hypertension. AB - The use of angiotensin receptor blockers (ARBs) represents a favorable approach for the control of blood pressure in patients with hypertension. Azilsartan medoxomil, a prodrug that undergoes rapid hydrolysis to its active moiety azilsartan, is an angiotensin AT(1) receptor antagonist with promising antihypertensive activity and a good safety profile. The agent has been evaluated as monotherapy and in combination with amlodipine or chlorthalidone in phase III trials in patients with essential hypertension. In 2011, azilsartan medoxomil was approved in the U.S. for the treatment of hypertension. PMID- 21971538 TI - Influence of race and gender on the presentation of eosinophilic esophagitis. AB - OBJECTIVES: Eosinophilic esophagitis (EoE) is thought to be more common among males and Caucasians, but little is known about the disease presentation among patients with different genders or racial backgrounds. The objective of this study was to determine the clinical, endoscopic, and histologic characteristics of patients with EoE of different genders or racial backgrounds. METHODS: We conducted a retrospective study of the University of North Carolina EoE clinicopathologic database between January 2000 and December 2008. Cases of EoE were defined per 2007 consensus guidelines and stratified by race and gender for comparison. RESULTS: In all, 208 incident EoE cases were identified (76% males, mean age 26 years, 82% Caucasian, and 12% African American). Caucasians were older at diagnosis than African Americans (27.1 vs. 19.0 years, P=0.05), less likely to present with failure-to-thrive (9 vs. 30%, P=0.002), and more likely to have esophageal rings (41 vs. 12%, P=0.005). These findings persisted after stratification by age. A higher proportion of males were diagnosed under the age of 18 as compared with females (48 vs. 64%, P=0.05). Males were more likely to report dysphagia and food impaction as symptoms (71 vs. 53%, P=0.02 and 35 vs. 20%, P=0.05, respectively), and these findings also persisted after stratification by age. The remainder of clinical, endoscopic, and histologic features did not differ by either race or gender. CONCLUSIONS: While age and dysphagia differed by gender and race among EoE patients, the majority of symptoms and findings were not different across groups, even after stratification by age. Clinicians should maintain a high index of suspicion for EoE, regardless of race or gender, and obtain esophageal biopsies to confirm the diagnosis. PMID- 21971540 TI - Collagenase clostridium histolyticum injection for the treatment of Dupuytren's contracture. AB - Collagenase clostridium histolyticum is a novel treatment for Dupuytren's contracture, approved by the U.S. Food and Drug Administration in February 2010. Prior to its availability, surgery was the only treatment for contracture related to this disorder. Dupuytren's disease is a benign, progressive fibroproliferative disorder affecting the palms of the hands. It is characterized by the formation of collagen- rich nodules and cords, which gradually shorten by the action of myofibroblasts, resulting in finger contractures. Intralesional use of clostridial collagenase has been evaluated in a total of 1,082 patients receiving 2,630 injections during its clinical development, including 2 large prospective, randomized, double-blind, placebo-controlled trials: Collagenase Option for Reduction of Dupuytren's I (CORD I) and CORD II. Both studies showed a statistically significant reduction in contracture compared to placebo and treatment was well-tolerated with the majority of adverse events self-limited. Serious adverse events related to collagenase activity were rare. Maximal improvement was seen in patients with less severe contractures and with contractures of the metacarpophalangeal joint. This first-in-class biologic, injectable clostridial collagenase histolyticum, provides a safe, effective alternative to surgery for patients with Dupuytren's contracture. PMID- 21971541 TI - Bevacizumab and ovarian cancer. AB - Epithelial ovarian cancer is the most lethal of gynecologic malignancies in the United States, with a significant proportion of patients with advanced disease achieving clinical remission with conventional treatment approaches, but dying of recurrence. Bevacizumab is a first-in-class antiangiogenic. This recombinant humanized monoclonal antibody neutralizes vascular endothelial growth factor (VEGF) and inhibits endothelial and tumor cell activation and proliferation. It has a low clearance and long elimination half-life, supporting a convenient 2- or 3-weekly dosing schedule. It is generally well tolerated, although trials have highlighted some toxicity-related concerns, notably gastrointestinal perforation. Phase III trials that evaluate overall survival are not yet mature, and cost effectiveness of bevacizumab is hotly debated. As more evidence for the role of anti-VEGF agents in augmenting therapy and inducing durable tumor dormancy continues to emerge, it is anticipated that antiangiogenic therapy will play an important role in the management ovarian malignancy. PMID- 21971542 TI - Tissue transglutaminase antibodies in celiac disease: focus on the pediatric population. AB - Celiac disease (CD) is an immune-mediated disorder induced by the ingestion of gluten in genetically susceptible individuals. The enzyme tissue transglutaminase (protein-glutamine gamma-glutamyltransferase 2; tTG) plays an important role in the pathogenesis of the disease and antibodies against tTG are used as serological markers for the diagnosis of CD. Discovery of tTG as the autoantigen for endomysial antibodies changed the diagnostic approach to patients with suspected CD and, importantly, made screening for CD more accurate and easier to perform. Studies in pediatric populations confirmed the high sensitivity and specificity of immunoglobulin A (IgA) tTG antibodies in the diagnosis of CD. The aim of this review is to summarize the data on the role of tTG in the pathogenesis of CD and to present current evidence on the accuracy of IgA tTG, IgG tTG and IgA tTG point-of-care tests in the diagnosis of CD in children. This review shows why IgA tTG antibodies replaced endomysial antibodies as the preferred serological marker due to the ease of their use, their high sensitivity and specificity, and the high correlation between high titers and intestinal mucosal lesions. PMID- 21971543 TI - A report from the 47th Annual Meeting of the American Society of Clinical Oncology (June 3-7, 2011 - Chicago, Illinois, USA). AB - Improving survival, as well as the quality of life and functioning of survivors, is the main objective of cancer therapy, for which a very large number of drugs are currently available or under development as therapeutic candidates. Information on many of these compounds was discussed during the 2011 American Society of Clinical Oncology (ASCO) meeting in Chicago. The number of news presentations discussed during the meeting was incredibly high, with plenary, oral abstract, poster discussion and general poster sessions filling room upon room. The following report provides a quick review of major new research into drug and support therapies for cancer as presented at the meeting. PMID- 21971544 TI - Arsenite induces cell transformation by reactive oxygen species, AKT, ERK1/2, and p70S6K1. AB - Arsenic is naturally occurring element that exists in both organic and inorganic formulations. The inorganic form arsenite has a positive association with development of multiple cancer types. There are significant populations throughout the world with high exposure to arsenite via drinking water. Thus, human exposure to arsenic has become a significant public health problem. Recent evidence suggests that reactive oxygen species (ROS) mediate multiple changes to cell behavior after acute arsenic exposure, including activation of proliferative signaling and angiogenesis. However, the role of ROS in mediating cell transformation by chronic arsenic exposure is unknown. We found that cells chronically exposed to sodium arsenite increased proliferation and gained anchorage-independent growth. This cell transformation phenotype required constitutive activation of AKT, ERK1/2, mTOR, and p70S6K1. We also observed these cells constitutively produce ROS, which was required for the constitutive activation of AKT, ERK1/2, mTOR, and p70S6K1. Suppression of ROS levels by forced expression of catalase also reduced cell proliferation and anchorage-independent growth. These results indicate cell transformation induced by chronic arsenic exposure is mediated by increased cellular levels of ROS, which mediates activation of AKT, ERK1/2, and p70S6K1. PMID- 21971545 TI - LC8 dynein light chain (DYNLL1) binds to the C-terminal domain of ATM-interacting protein (ATMIN/ASCIZ) and regulates its subcellular localization. AB - LC8 dynein light chain (now termed DYNLL1 and DYNLL2 in mammals), a dimeric 89 amino acid protein, is a component of the dynein multi-protein complex. However a substantial amount of DYNLL1 is not associated to microtubules and it can thus interact with dozens of cellular and viral proteins that display well-defined, short linear motifs. Using DYNLL1 as bait in a yeast two-hybrid screen of a human heart library we identified ATMIN, an ATM kinase-interacting protein, as a DYNLL1 binding partner. Interestingly, ATMIN displays at least 18 SQ/TQ motifs in its sequence and DYNLL1 is known to bind to proteins with KXTQT motifs. Using pepscan and yeast two-hybrid techniques we show that DYNLL1 binds to multiple SQ/TQ motifs present in the carboxy-terminal domain of ATMIN. Recombinant expression and purification of the DYNLL1-binding region of ATMIN allowed us to obtain a polypeptide with an apparent molecular mass in gel filtration close to 400 kDa that could bind to DYNLL1 in vitro. The NMR data-driven modelled complexes of DYNLL1 with two selected ATMIN peptides revealed a similar mode of binding to that observed between DYNLL1 and other peptide targets. Remarkably, co-expression of mCherry-DYNLL1 and GFP-ATMIN mutually affected intracellular protein localization. In GFP-ATMIN expressing-cells DNA damage induced efficiently nuclear foci formation, which was partly impeded by the presence of mCherry DYNLL1. Thus, our results imply a potential cellular interference between DYNLL1 and ATMIN functions. PMID- 21971546 TI - GTP depletion synergizes the anti-proliferative activity of chemotherapeutic agents in a cell type-dependent manner. AB - Mycophenolic acid (MPA) depletes intracellular GTP by blocking de novo guanine nucleotide synthesis. GTP is used ubiquitously for DNA/RNA synthesis and as a signaling molecule. Here, we made a surprising discovery that the anti proliferative activity of MPA acts synergistically with specific chemotherapeutic agents in a cell type-dependent manner. In MDA-MB-231 cells, MPA shows an extremely potent synergy with 5-FU but not with doxorubicin or etoposide. The synergy between 5-FU and MPA works most effectively against the highly tumorigenic mammary tumor cells compared to the less tumorigenic ones, and does not work in the non-breast cancer cell types that we tested, with the exception of PC3 cells. On the contrary, MPA shows the highest synergy with paclitaxel but not with 5-FU in SCC-25 cells, derived from oral squamous cell carcinomas. Mechanistically, the synergistic effect of MPA on 5-FU in MDA-MB-231 cells can be recapitulated by inhibiting the RNA polymerase-I activity and requires the expression of nucleostemin. This work reveals that the synergy between MPA and anti-proliferative agents is determined by cell type-dependent factors. PMID- 21971547 TI - Disconnected Interacting Protein 1 binds with high affinity to pre-tRNA and ADAT. AB - Disconnected Interacting Protein 1 (DIP1), a member of the double-stranded RNA binding protein family based on amino acid sequence, was shown previously to form complexes with multiple transcription factors in Drosophila melanogaster. To explore this protein further, we have undertaken sedimentation equilibrium experiments that demonstrate that DIP1-c (longest isoform of DIP1) is a dimer in solution, a characteristic common to other members of the dsRNA-binding protein family. The closest sequence identity for DIP1 is found within the dsRBD sequences of RNA editase enzymes. Consistent with this role, we demonstrate binding of DIP1-c to a potential physiological RNA target: pre-tRNA. In addition, DIP1-c was shown to interact with ADAT, a tRNA deaminase that presumably modifies pre-tRNAs. From these data, we hypothesize that DIP1 may serve an integrator role by binding its dsRNA ligand and recruiting protein partners for the appropriate metabolism of the bound RNA. PMID- 21971548 TI - Mnl2, a novel component of the ER associated protein degradation pathway. AB - In eukaryotes, membrane and soluble proteins of the secretory pathway enter the endoplasmic reticulum (ER) after synthesis in an unfolded state. Directly after entry, most proteins are modified with glycans at suitable glycosylation sites and start to fold. A protein that cannot fold properly will be degraded in a process called ER associated degradation (ERAD). Failures in ERAD, either by loss of function or by premature degradation of proteins, are a cause of severe diseases. Therefore, the search for novel ERAD components to gain better insight in this process is of high importance. Carbohydrate trimming is a relevant process in ER quality control. In this work a novel putative yeast mannosidase encoded by the open reading frame YLR057W was identified and named Mnl2. Deletion of MNL2 diminished the degradation efficiency of misfolded CPY(*) in the absence of the cognate mannosidase Mnl1, indicating a specific role in ERAD. PMID- 21971550 TI - Structural modeling of SoxF protein from Chlorobium tepidum: an approach to understand the molecular basis of thiosulfate oxidation. AB - Microbial redox reactions of inorganic sulfur compounds play a vital role in balancing the turnover of this element in the environment. These vital reactions are carried out by the enzyme system encoded by the sox operon. The central player of the sulfur oxidation biochemistry is the SoxY-Z protein complex. Another protein called SoxF having sulfide dehydrogenase activity has the ability to reactivate the inactivated SoxY-Z protein complex. This SoxF protein is obtained from the sox operon of Chlorobium tepidium. In the present work an attempt has been made to understand the structural details of the activity of SoxF protein. A plausible biochemical mechanism has been predicted regarding the involvement of the SoxF protein in biological sulfur anion oxidation process. Since this is the first report regarding the structural biology of SoxF protein this study may shed light in the hitherto unknown molecular biochemistry of sulfur anion oxidation by sox operon. PMID- 21971549 TI - Mechanism of translocation of uracil-DNA glycosylase from Escherichia coli between distributed lesions. AB - Uracil-DNA glycosylase (Ung) is a DNA repair enzyme that excises uracil bases from DNA, where they appear through deamination of cytosine or incorporation from a cellular dUTP pool. DNA repair enzymes often use one-dimensional diffusion along DNA to accelerate target search; however, this mechanism remains poorly investigated mechanistically. We used oligonucleotide substrates containing two uracil residues in defined positions to characterize one-dimensional search of DNA by Escherichia coli Ung. Mg(2+) ions suppressed the search in double-stranded DNA to a higher extent than K(+) likely due to tight binding of Mg(2+) to DNA phosphates. Ung was able to efficiently overcome short single-stranded gaps within double-stranded DNA. Varying the distance between the lesions and fitting the data to a theoretical model of DNA random walk, we estimated the characteristic one-dimensional search distance of ~100 nucleotides and translocation rate constant of ~2*10(6) s(-1). PMID- 21971551 TI - Self-powered electroporation using a singularity-induced nano-electroporation configuration. AB - This study demonstrates the feasibility of creating a self-powered (galvanic) electroporation device using the singularity-induced nano-electroporation configuration. Using this configuration, the electric field in a galvanic electrochemical cell can be amplified and used for electroporation. A secondary current distribution model of a self-powered electroporation device shows that the device can create both reversible and irreversible electroporation-inducing electric field magnitudes, and generate a small amount of power. PMID- 21971552 TI - Simulated microgravity using a rotary cell culture system promotes chondrogenesis of human adipose-derived mesenchymal stem cells via the p38 MAPK pathway. AB - Mesenchymal stem cells (MSCs) are multi-potent, and the chondrogenesis of MSCs is affected by mechanical stimulation. The aim of this study was to investigate, using a rotary cell culture system (RCCS) bioreactor, the effects of microgravity on the chondrogenic differentiation of human adipose-derived MSCs (ADSCs), which were cultured in pellets with or without the chondrogenic growth factor TGF beta1. In addition, we evaluated the role of the p38 MAPK pathway in this process. The real-time PCR and histological results show that microgravity has a synergistic effect on chondrogenesis with TGF-beta1. The p38 MAPK pathway was activated by TGF-beta1 alone and was further stimulated by microgravity. Inhibition of p38 activity with SB203580 suppressed chondrocyte-specific gene expression and matrix production. These findings suggest that the p38 MAPK signal acts as an essential mediator in the microgravity-induced chondrogenesis of ADSCs. PMID- 21971553 TI - Somatic hypermutation and the discovery of A-to-I RNA editing sites? PMID- 21971554 TI - Ebf1 deficiency causes increase of Muller cells in the retina and abnormal topographic projection at the optic chiasm. AB - The Ebf transcription factors play important roles in the developmental processes of many tissues. We have shown previously that four members of the Ebf family are expressed during mouse retinal development and are both necessary and sufficient to specify multiple retinal cell fates. Here we describe the changes in cell differentiation and retinal ganglion cell (RGC) projection in Ebf1 knockout mice. Analysis of marker expression in Ebf1 null mutant retinas reveals that loss of Ebf1 function causes a significant increase of Muller cells. Moreover, there is an obvious decrease of ipsilateral and retinoretinal projections of RGC axons at the optic chiasm, whereas the contralateral projection significantly increases in the mutant mice. These data together suggests that Ebf1 is required for suppressing the Muller cell fate during retinogenesis and important for the correct topographic projection of RGC axons at the optic chiasm. PMID- 21971555 TI - Cell death pathology: the war against cancer. AB - Programmed cell death was a fundamental discovery, awarded with the Nobel price in 2002 to Sulston, Brenner and Horvitz. Since then it has been clear that alteration of apoptotic pathways is a common feature of tumors, enabling cancer cells to survive chemotherapeutic interventions. Thus, apoptosis is an attractive target in cancer therapy, with the aim to revert the cancer-related alterations of the cell death machinery. Here, we overview the fundamental apoptotic pathways and summarize the attempts to target apoptosis to restore cell death in cancer cells with a special focus on the p53-family and autophagy. PMID- 21971556 TI - Temporal assessment of ribose treatment on self-assembled articular cartilage constructs. AB - Articular cartilage cannot repair itself in response to degradation from injury or osteoarthritis. As such, there is a substantial clinical need for replacements of damaged cartilage. Tissue engineering aims to fulfill this need by developing replacement tissues in vitro. A major goal of cartilage tissue engineering is to produce tissues with robust biochemical and biomechanical properties. One technique that has been proposed to improve these properties in engineered tissue is the use of non-enzymatic glycation to induce collagen crosslinking, an attractive solution that may avoid the risks of cytotoxicity posed by conventional crosslinking agents such as glutaraldehyde. The objectives of this study were (1) to determine whether continuous application of ribose would enhance biochemical and biomechanical properties of self-assembled articular cartilage constructs, and (2) to identify an optimal time window for continuous ribose treatment. Self-assembled constructs were grown for 4 weeks using a previously established method and were subjected to continuous 7-day treatment with 30 mM ribose during culture weeks 1, 2, 3, or 4, or for the entire 4-week culture. Control constructs were grown in parallel, and all groups were evaluated for gross morphology, histology, cellularity, collagen and sulfated glycosaminoglycan (GAG) content, and compressive and tensile mechanical properties. Compared to control constructs, it was found that treatment with ribose during week 2 and for the entire duration of culture resulted in significant 62% and 40% increases in compressive stiffness, respectively; significant 66% and 44% increases in tensile stiffness; and significant 50% and 126% increases in tensile strength. Similar statistically significant trends were observed for collagen and GAG. In contrast, constructs treated with ribose during week 1 had poorer biochemical and biomechanical properties, although they were significantly larger and more cellular than all other groups. We conclude that non-enzymatic glycation with ribose is an effective method for improving tissue engineered cartilage and that specific temporal intervention windows exist to achieve optimal functional properties. PMID- 21971557 TI - Antioxidant treatment may protect pancreatic beta cells through the attenuation of islet fibrosis in an animal model of type 2 diabetes. AB - Islet fibrosis could be important in the progression of pancreatic beta cell failure in type 2 diabetes. It is known that oxidative stress is involved in the pancreatic fibrosis through the activation of pancreatic stellate cells. However, no study has investigated the in vivo effects of antioxidants on islet fibrogenesis in type 2 diabetes. In this study, antioxidants (taurine or tempol) were administered in drinking water to Otsuka Long-Evans Tokushima Fatty rats, an animal model of type 2 diabetes, for 16 weeks. An intraperitoneal glucose tolerance test revealed that the blood glucose levels after the glucose injection were decreased by the antioxidants. The insulin secretion after the glucose injection, which was markedly reduced in the rats, was also restored by the antioxidants. Beta cell mass and pancreatic insulin content were greater in the rats treated with the antioxidants than in the untreated rats. Beta cell apoptosis was attenuated in the rats by the antioxidants. Finally, islet fibrosis and the activation of pancreatic stellate cells were markedly diminished in the rats by the antioxidants. Our data suggest that antioxidants may protect beta cells through the attenuation of both islet fibrosis and beta cell apoptosis in type 2 diabetes. PMID- 21971558 TI - Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth. AB - Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth of undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures. PMID- 21971559 TI - Are there opportunities for chemotherapy in the treatment of hepatocellular cancer? AB - Hepatocellular cancer is a significant global health problem yet the prognosis for the majority of patients has not changed significantly over the past few decades. For patients with advanced disease, sorafenib is currently the standard of care providing a survival advantage of 2-3 months in selected patients. Cytotoxic chemotherapy has been used for over 30 years but definite evidence that it prolongs survival has been lacking. Resistance remains a significant barrier for both targeted and cytotoxic agents and an understanding of the underlying mechanisms is critical if outcomes are to be improved. Here, we summarise the past and current data that constitute the evidence base for chemotherapy in HCC, review the causes of chemoresistance and suggest strategies to overcome these barriers. PMID- 21971561 TI - A four coordinate parent imide via a titanium nitridyl. AB - Treatment of d(1) [(nacnac)TiCl(Ntol(2))] with NaN(3) results in NaCl formation and N(2) ejection to yield the first four coordinate, parent imide [(nacnac)Ti=NH(Ntol(2))] (nacnac(-)=[ArNC(CH(3))](2)CH, Ar = 2,6-iPr(2)C(6)H(3), tol = 4-CH(3)C(6)H(4)). PMID- 21971562 TI - Chemoselective oxidation of primary alcohols catalysed by Ce(III)-complex intercalated LDH using molecular oxygen at room temperature. AB - Herein we describe the preparation of an efficient heterogeneous catalyst consisting of an anionic Ce(III)-complex immobilized Zn/Al-layered double hydroxide (LDH) and its use in the catalytic liquid phase oxidation of primary alcohols using molecular O(2) at room temperature. Various primary alcohols could be transformed to their corresponding aldehydes in good to excellent yields using the set of optimal conditions. The heterogeneous catalytic system can also be recovered and reused for several cycles without a significant loss of catalytic activity. PMID- 21971563 TI - Prospects for ultracold carbon via charge exchange reactions and laser cooled carbides. AB - Strategies to produce an ultracold sample of carbon atoms are explored and assessed with the help of quantum chemistry. After a brief discussion of the experimental difficulties using conventional methods, two strategies are investigated. The first attempts to exploit charge exchange reactions between ultracold metal atoms and sympathetically cooled C(+) ions. Ab initio calculations including electron correlation have been conducted on the molecular ions [LiC](+) and [BeC](+) to determine whether alkali or alkaline earth metals are a suitable buffer gas for the formation of C atoms but strong spontaneous radiative charge exchange ensure they are not ideal. The second technique involves the stimulated production of ultracold C atoms from a gas of laser cooled carbides. Calculations on LiC suggest that the alkali carbides are not suitable but the CH radical is a possible laser cooling candidate thanks to very favourable Frank-Condon factors. A scheme based on a four pulse STIRAP excitation pathway to a Feshbach resonance is outlined for the production of atomic fragments with near zero centre of mass velocity. PMID- 21971560 TI - Novel glutamatergic agents for major depressive disorder and bipolar disorder. AB - Mood disorders such as major depressive disorder (MDD) and bipolar disorder (BPD) are common, chronic, recurrent mental illnesses that affect the lives and functioning of millions of individuals worldwide. Growing evidence suggests that the glutamatergic system is central to the neurobiology and treatment of these disorders. Here, we review data supporting the involvement of the glutamatergic system in the pathophysiology of mood disorders as well as the efficacy of glutamatergic agents as novel therapeutics. PMID- 21971564 TI - Cinacalcet efficacy in patients with moderately severe primary hyperparathyroidism according to the European Medicine Agency prescription labeling. AB - BACKGROUND: Patients with primary hyperparathyroidism (PHPT) with contraindications to parathyroidectomy (PTx) or persistent PHPT have few non surgical options. AIM: The aim of the study was to investigate the efficacy of cinacalcet in reducing serum calcium in patients with PHPT, for whom PTx would be indicated according to serum calcium levels, but in whom PTx is not clinically appropriate or is contraindicated [European Medicines Agency (EMA) prescription labeling]. SUBJECTS AND METHODS: The study (open-label prospective, conducted in a single tertiary center) included 12 sporadic and 2 multiple endocrine neoplasia type 1 PHPT patients with serum calcium greater than 11.2 mg/dl. Cinacalcet was administered in increasing doses until normal serum calcium was reached or side effects preventing a further increase occurred. Serum calcium, PTH, phosphate, 25OHD, markers of bone turnover, 24h-urinary calcium and areal bone mineral density (BMD) were measured. Safety biochemical indices and adverse events were monitored. RESULTS: The maintenance cinacalcet dose [median 30 mg twice daily (range 30 daily-60 mg twice daily)] was maintained constant during follow-up (median 12 months). Mean+/-SE baseline serum calcium was 12.2+/-0.3 mg/dl. Serum calcium decreased by at least 1 mg/dl in all patients and normalized in 10. Serum calcium at the last observation was 9.9+/-0.2 mg/dl (p<0.0001 vs baseline). PTH decreased by 17.1% compared to baseline (p=0.13), and never reached a normal value. BMD was unchanged. Adverse events occurred in 6 patients (43%) and required treatment withdrawal in 2. CONCLUSIONS: Cinacalcet reduced and often normalized serum calcium in PHPT patients who met the EMA labeling. PMID- 21971565 TI - Tracheal papillomatosis: what do we know so far? AB - Tracheal papillomatosis (TP) is a benign condition characterized by papillomatous growth of the bronchial epithelium that involves the trachea. This abnormal growth is a result of infection with human papilloma virus (HPV). Two subtypes of HPV were found in most cases of TP, HPV-6 and HPV-11. TP, presents in two forms, the juvenile onset (JO) or adult onset (AO). The clinical presentation is typically nonspecific and it ranges from mild symptoms like cough to life threatening conditions like upper airway obstruction. Treatment depends on the location of the papillomas and age of the patient and the plan of therapy is usually made on an individual basis. Treatment can range from observation with symptomatic control to specific medical therapy and multiple surgeries in case of recurrence or progressively worsening disease. The recent invention of HPV vaccine is expected to be the first step in eradicating respiratory papillomatosis. PMID- 21971566 TI - Availability of vitamin D photoconversion weighted UV radiation in southern South America. AB - Ultraviolet radiation (UVR) plays a key role in several biological functions, including human health. Skin exposure to UVR is the main factor in vitamin D photoconversion. There is also evidence relating low levels of vitamin D with certain internal cancers, mainly colon, breast and prostate, as well as other diseases. Several epidemiological studies have shown an inverse relationship between the above-mentioned diseases and latitude, in accordance with the ultraviolet radiation latitudinal gradient. The aim of this study is to determine whether UV irradiance levels in the southern South America are sufficient to produce suitable levels of vitamin D year around. For this purpose, vitamin D photoconversion weighted-irradiance was analyzed between S.S. de Jujuy (24.17 degrees S, 65.02 degrees W) and Ushuaia (54 degrees 50'S, 68 degrees 18'W). In addition to irradiance, skin type and area of body exposed to sunlight are critical factors in vitamin D epidemiology. Due to a broad ethnic variability, it was assumed that the skin type in this region varies between II and V (from the most to the less sensitive). All sites except South Patagonia indicate that skin II under any condition of body area exposure and skin V when exposing head, hands, arms and legs, would produce suitable levels of vitamin D year round (except for some days in winter at North Patagonian sites). At South Patagonian sites, minimum healthy levels of vitamin D year round can be reached only by the more sensitive skin II type, if exposing head, hands, arms and legs, which is not a realistic scenario during winter. At these southern latitudes, healthy vitamin D levels would not be obtained between mid May and beginning of August if exposing only the head. Skin V with head exposure is the most critical situation; with the exception of the tropics, sun exposure would not produce suitable levels of vitamin D around winter, during a time period that varies with latitude. Analyzing the best exposure time during the day in order to obtain a suitable level of vitamin D without risk of sunburn, it was concluded that noon is best during winter, as determined previously. For skin type II when exposing head, exposure period in winter varies between 30 and 130 min, according to latitude, except for South Patagonian sites. During summer, noon seems to be a good time of day for short periods of exposure, while during leisure times, longer periods of exposure without risk of sunburn are possible at mid-morning and mid-afternoon. At 3 h from noon, solar zenith angles are almost the same for sites between the tropics and North Patagonia, and at 4 h from noon, for all sites. Then, in these cases, the necessary exposure periods varied slightly between sites, only due to meteorological differences. PMID- 21971570 TI - Synthesis and characterization of oxorhenium(v) diamido pyridine complexes that catalyze oxygen atom transfer reactions. AB - The detailed syntheses of complexes 1-4, Re(O)(X)(DAP) (X = Me, 1; Cl, 2; I, 3; OTf (triflate), 4) incorporating the diamido pyridine (DAP) ancillary ligand (2,6 bis((mesitylamino)methyl)pyridine) are described and shown to be effective catalysts for oxygen atom transfer (OAT) reactions of PyO to PPh(3). The catalytic activities are as follows: 4~3 > 2 > 1. The observed electronic trend is consistent with the turnover limiting reduction of the proposed Re(VII) dioxo intermediate, Re(O)(2)(X)(DAP), during the catalytic cycle. The catalytic activity of complexes 1-3 was compared to previously published diamido amine (DAAm) oxorhenium complexes of the type Re(O)(X)(DAAm) (X = Me, 5; Cl, 6; I, 7 and DAAm = N,N-bis(2-arylaminoethyl)methylamine) which exhibit hydrolytic degradation during the catalytic reaction. Complexes 1-3 displayed higher turnover frequencies compared to 5-7. This higher catalytic activity was attributed to the more rigid DAP ligand backbone, which makes the complexes less susceptible to decomposition. However, another decomposition pathway was proposed for this catalytic system due to the observation of Re(O)(3)((MesNCH(2))(MesNCH)NC(5)H(3)) 8 in which one arm of the DAP ligand is oxidized. PMID- 21971569 TI - Tubeimoside-1 induces G2/M phase arrest and apoptosis in SKOV-3 cells through increase of intracellular Ca2+ and caspase-dependent signaling pathways. AB - Tubeimoside-1 (TBMS1) extracted from Bolbostemma paniculatum (Maxim), is a traditional Chinese herb with anticancer potential. It induces apoptosis in a number of human carcinoma cell lines, but the mechanism has remained unclear. In the present study, we investigated the pro-apoptotic activity of TBMS1 against SKOV-3 cell lines and the underlying mechanisms. Treatment with TBMS1 resulted in dose- and time-dependent inhibition of proliferation, led to arrest in phase G2/M of the cell cycle and increased the levels of intracellular Ca2+. Furthermore, TBMS1 up-regulated the levels of the glucose-regulated protein 78/immunoglobuin heavy chain binding protein (GRP78/Bip), C/EBP homologous protein (CHOP), Bax, and cleaved caspase-3 and down-regulated the levels of Bcl-2. It was shown to be linked to activation of the extracellular signal-regulated kinase (ERK) 1 and 2 signal transduction pathway. A decrease in Bcl-2/Bax ratio with increased expression of caspase-3, and intracellular Ca2+ provide compelling evidence that TBMS1-induced apoptosis is mediated by the mitochondrial pathway. The results of the present study suggest that TBMS1 has immense potential in cancer prevention and therapy based on its antiproliferative and apoptosis inducing effects. PMID- 21971567 TI - Immunology and immunotherapy of neuroblastoma. AB - PURPOSE: This review demonstrates the importance of immunobiology and immunotherapy research for understanding and treating neuroblastoma. PRINCIPAL RESULTS: The first suggestions of immune system-neuroblastoma interactions came from in vitro experiments showing that lymphocytes from patients were cytotoxic for their own tumor cells and from evaluations of tumors from patients that showed infiltrations of immune system cells. With the development of monoclonal antibody (mAb) technology, a number of mAbs were generated against neuroblastoma cells lines and were used to define tumor associated antigens. Disialoganglioside (GD2) is one such antigen that is highly expressed by virtually all neuroblastoma cells and so is a useful target for both identification and treatment of tumor cells with mAbs. Preclinical research using in vitro and transplantable tumor models of neuroblastoma has demonstrated that cytotoxic T lymphocytes (CTLs) can specifically recognize and kill tumor cells as a result of vaccination or of genetic engineering that endows them with chimeric antigen receptors. However, CTL based clinical trials have not progressed beyond pilot and phase I studies. In contrast, anti-GD2 mAbs have been extensively studied and modified in pre clinical experiments and have progressed from phase I through phase III clinical trials. Thus, the one proven beneficial immunotherapy for patients with high-risk neuroblastoma uses a chimeric anti-GD2 mAb combined with IL-2 and GM-CSF to treat patients after they have received intensive cyto-reductive chemotherapy, irradiation, and surgery. Ongoing pre-clinical and clinical research emphasizes vaccine, adoptive cell therapy, and mAb strategies. Recently it was shown that the neuroblastoma microenvironment is immunosuppressive and tumor growth promoting, and strategies to overcome this are being developed to enhance anti tumor immunotherapy. CONCLUSIONS: Our understanding of the immunobiology of neuroblastoma has increased immensely over the past 40 years, and clinical translation has shown that mAb based immunotherapy can contribute to improving treatment for high-risk patients. Continued immunobiology and pre-clinical therapeutic research will be translated into even more effective immunotherapeutic strategies that will be integrated with new cytotoxic drug and irradiation therapies to improve survival and quality of life for patients with high-risk neuroblastoma. PMID- 21971572 TI - Influence of various polishing methods on pulp temperature : an in vitro study. AB - OBJECTIVE: After orthodontic debonding, adhesive removal can lead to rises in pulp temperature, causing histological changes or pulp necrosis. The objective of this study was to measure increases in pulp temperature during adhesive removal using different instruments and various cooling procedures. MATERIALS AND METHODS: A thermoelement was introduced into the pulp chamber of 10 human incisors. The teeth were immersed in a 36 degrees C water bath up to the cementoenamel junction. Two carbide burs, one polishing disk and two rubber points were used for polishing. All measurements were taken over a 10 s period by a single investigator, under slight pressure and with constant motion. Three cooling procedures were examined: no cooling, air cooling and water cooling. Pulp temperatures were measured before polishing and after 10 s of polishing. RESULTS: Without cooling, the two rubber points revealed clinically relevant temperature increases of 6.1 degrees C and 12.4 degrees C. Cooling with air and with water reduced pulp temperature in conjunction with all polishing methods. Air cooling was most efficient, except in combination with the polishing disk. CONCLUSION: Under these study conditions, carbide burs and polishing disks can be used safely and without risk to the pulp, even without cooling. On the other hand, rubber points cause a marked increase in pulp temperature when used without cooling. PMID- 21971574 TI - Alteration of protein folding and degradation in motor neuron diseases: Implications and protective functions of small heat shock proteins. AB - Motor neuron diseases (MNDs) are neurodegenerative disorders that specifically affect the survival and function of upper and/or lower motor neurons. Since motor neurons are responsible for the control of voluntary muscular movement, MNDs are characterized by muscle spasticity, weakness and atrophy. Different susceptibility genes associated with an increased risk to develop MNDs have been reported and several mutated genes have been linked to hereditary forms of MNDs. However, most cases of MNDs occur in sporadic forms and very little is known on their causes. Interestingly, several molecular mechanisms seem to participate in the progression of both the inherited and sporadic forms of MNDs. These include cytoskeleton organization, mitochondrial functions, DNA repair and RNA synthesis/processing, vesicle trafficking, endolysosomal trafficking and fusion, as well as protein folding and protein degradation. In particular, accumulation of aggregate-prone proteins is a hallmark of MNDs, suggesting that the protein quality control system (molecular chaperones and the degradative systems: ubiquitin-proteasome-system and autophagy) are saturated or not sufficient to allow the clearance of these altered proteins. In this review we mainly focus on the MNDs associated with disturbances in protein folding and protein degradation and on the potential implication of a specific class of molecular chaperones, the small heat shock proteins (sHSPs/HSPBs), in motor neuron function and survival. How boosting of specific HSPBs may be a potential useful therapeutic approach in MNDs and how mutations in specific HSPBs can directly cause motor neuron degeneration is discussed. PMID- 21971573 TI - Shear bond strengths of seven self-etching primers after thermo-cycling. AB - OBJECTIVE: Self-etching primers are widely used in restorative dentistry. However, only one primer has been developed for orthodontic applications. The objective of this study was to assess the suitabiliy of restorative self-etching primers on unabraded enamel. MATERIAL AND METHODS: Seven self-etching primers (TransbondTM SEP +, Xeno(r) III, ClearfilTM SE, Futurabond(r) NR, One Coat, M Bond and OptiBond(r)) were compared with two conventionally-etched control groups (TransbondTM MIP). All groups with the exception of one of the two control groups underwent thermo-cycling (1000x, 5-55 degrees C). Bovine teeth stored in physiological saline solution were used for the purpose of this study. RESULTS: Both before and after thermo-cycling, the control groups presented very similar shear strengths which did not differ significantly from each other or from the TransbondTM SEP + and ClearfilTM SE specimens. During thermo-cycling, all groups except the control group and the TransbondTM SEP + specimens displayed losses from the shear bodies. These losses occurred on all of the OptiBond(r) samples. The adhesive remnant index (ARI) and enamel tear-outs correlated closely with the adhesive values. CONCLUSIONS: Our adhesive value assessments support the conclusion that only TransbondTM SEP + and ClearfilTM SE can be recommended for clinical use. PMID- 21971575 TI - Comparative evaluation of isosorbide mononitrate and alendronate in management of postmenopausal osteoporosis. AB - BACKGROUND: Osteoporosis, a skeletal disorder that adversely affects bone strength , is common among postmenopausal women primarily due to reduced ovarian estrogens. PURPOSE: The present study was taken up to evaluate the role of isosorbide mononitrate (IMN) in the management of postmenopausal osteoporosis and to compare its efficacy with that of alendronate. METHODS: This prospective systematic randomized study was conducted on 90 postmenopausal women with lumbar spine BMD >2.5 SD below the young adult reference range. The participants received either Tab Alendronate 70 mg orally, once weekly (Group I) or Tab IMN 40 mg orally once daily (Group II) for 9 months, in addition to 500 mg of oral calcium daily. The BMD of the lumbar spine was measured using DEXA scan at enrolment and after 9 months. The data was analyzed by Student's t test and Chi square test. RESULTS: The mean baseline BMD was 0.67 + 0.097 and 0.68 + 0.067 g/cm(2) in Group I and II, respectively. An increase of 11.94% in the mean BMD was noted after 9 months of treatment with alendronate as against 8.82% with IMN. Headache, flushing and palpitations in Group II and nausea, epigastric pain and heart burn in Group I were the most common adverse effects. CONCLUSION: IMN has a beneficial effect on bone turnover in cases of postmenopausal osteoporosis and that the effect is comparable to that of alendronate. IMN is a promising and safe alternative to alendronate for the management of postmenopausal osteoporosis. PMID- 21971576 TI - Increased rate of cesarean section in primiparous women aged 40 years or more: a single-center study in Japan. AB - PURPOSE: To investigate perinatal outcomes in late primiparous women aged 35-39 and >=40 years. Our main research question: "Was the rate of cesarean section similar between these 2 groups of advanced maternal age?" METHODS: Primiparous women aged >=35 years, who delivered in our center between April 2004 and March 2007, were enrolled in this study. They were divided into two groups: women aged 35-39 years and those aged >=40 years. Antenatal complications, deliveries, and neonatal outcomes were analyzed. Fetal abnormalities, abortions, and multiple gestations were excluded. RESULTS: We assessed 752 cases (35-39 years, 610 cases; >=40 years, 142 cases). Incidence of cesarean section (CS) was significantly higher in pregnant women aged >=40 years (P < 0.01). The CS rate amounted to 50.0% of all deliveries in this age group. Among patients with labor deliveries, the CS rate was also significantly higher in the older age group (P < 0.05). With regard to indication for CS with labor deliveries, the rate of non-progressive labor/dystocia was 19.4% in primiparous women aged >=40 years and 11.0% in those aged 35-39 years, respectively (P < 0.05). In contrast, the rates of antenatal complications were not different between the two groups, except for gestational diabetes or leiomyoma. No significant differences between the two groups could be found for neonatal outcomes such as birth weight, Apgar score, and admission to neonatal intensive care unit. CONCLUSIONS: CS rate was 50.0% in primiparous women aged >=40 years. In addition, CS caused by dystocia was almost twice as frequent in primiparous women aged >=40 years as in women aged 35-39 years. Among late pregnancies, primiparous women aged 40 years and older had higher risk of CS. PMID- 21971577 TI - Primary peritoneal borderline mucinous cystadenofibroma. PMID- 21971578 TI - Epidemiology, risk and outcomes of venous thromboembolism in cancer. AB - Cancer is associated with a fourfold increased risk of venous thromboembolism (VTE). The risk of VTE varies according to the type of malignancy (i. e. pancreatic cancer, brain cancer, lymphoma) and its disease stage and individual factors (i. e. sex, race, age, previous VTE history, immobilization, obesity). Preventing cancer-associated VTE is important because it represents a significant cause of morbidity and mortality. In order to identify cancer patient at particularly high risk, who need thromboprophylaxis, risk prediction models have become available and are under validation. These models include clinical risk factors, but also begin to incorporate biological markers. The major American and European scientific societies have issued their recommendations to guide the management of VTE in patients with cancer. In this review the principal aspects of epidemiology, risk factors and outcome of cancer-associated VTE are summarized. PMID- 21971579 TI - Peripheral blood mono-nuclear cells derived from Alzheimer's disease patients show elevated baseline levels of secreted cytokines but resist stimulation with beta-amyloid peptide. AB - OBJECTIVES: Among several other factors, the neuro-toxic beta-amyloid peptide (betaAP)-induced inflammatory mechanisms have also been implicated in the pathogenesis of Alzheimer's dementia (AD). Cytokines have recently emerged as prime candidates underlying this immune reaction. The purpose of this study was to evaluate the inflammatory response of peripheral blood mono-nuclear cells (PBMC) in AD. DESIGN: Cross-sectional (observational) study. SETTING: Behavioral and cognitive neurology clinic of the Universidade Federal de Minas Gerais in Belo Horizonte, Brazil. PARTICIPANTS: AD patients (n=19), healthy elderly (n=19) and young (n=14) individuals. MEASUREMENTS: Cytokine levels were assessed by enzyme-linked immuno-sorbent assay (ELISA) after exposing cells to a broad range of betaAP concentrations (10(-4)-10(-10)M) as a stimulus. AD samples were weighed against leukocytes harvested from non-demented young and elderly subjects. RESULTS: Cytokine production of PBMCs in the youth was characterized by low baseline levels when compared to cells from the older generation. In the aging population, AD cells were distinguished from the healthy elderly sub-group by an even higher basal cytokine secretion. The low resting concentration in young individuals was markedly increased after treatment with betaAP, however cells from the elderly, irrespective of their disease status, showed unchanged cytokine release following betaAP administration. Non-specific activation of PBMCs with anti-CD3/CD28 antibodies resulted in elevated interleukin (IL)-1beta concentrations in AD. CONCLUSIONS: These results demonstrate a general over production of cytokines and resistance to betaAP in the old comparison group, with a more pronounced disruption/boosted pattern in AD. Our findings are in line with the hypothesis of "inflammaging", i.e. an enhanced inflammatory profile with normal aging and a further perturbed environment in AD. The observed cytokine profiles may serve as diagnostic biomarkers in dementia. PMID- 21971580 TI - Neurite outgrowth is differentially impacted by distinct immune cell subsets. AB - Axonal damage can occur in the central nervous system following trauma, during the course of autoimmune and neurodegenerative disease and during viral and bacterial infections. The degree of axonal damage and absence of spontaneous repair are major determinants of long-term clinical outcome. While inflammation is a common feature of these conditions, the impact of particular immune cell subsets and their products on injured axons is not fully known. To investigate the impact of immune cells on neuronal viability and axonal repair, we developed an in vitro culture system in which neurons are exposed to mixed or distinct immune cell subsets. We find that total peripheral blood mononuclear cells (PBMCs) have a significant inhibitory effect on neurite outgrowth that is independent of apoptosis. Using isolated immune cells subsets, we demonstrate that activated CD4+ T cells enhance neurite outgrowth while activated NK cells and CD8+ T cells inhibit neurite outgrowth. We find that NK cell inhibition of neuronal outgrowth is dependent on MAPK activity. Our findings describe heterogeneous effects of individual immune cell subsets on neuronal growth and offer important insights into the cellular and molecular mechanisms that may impact axonal repair in inflammatory CNS conditions. PMID- 21971581 TI - Synthesis and evaluation of physicochemical properties of cross-linked sago starch. AB - Highly substituted sago starch phosphate was synthesized using POCl(3) as cross linking reagent. Titrimetric and Fourier transform infra red (FT-IR) spectral analysis were used to characterize the substitution. Studying the different factors affecting the reaction parameters showed that the optimal conditions for starch phosphorylation were: 4h reaction time and reagent concentration 1.5% (w/w). The physicochemical properties of cross-linked sago starch (CLSS) were done using Scanning electron micrograph (SEM), X-ray powder diffractometer (XRD and Thermogravimetric analysis (TGA). The results revealed that crystalline nature of native sago starch was transformed after cross-linking. TGA report exhibited higher thermal stability, which makes it suitable for various industrial applications. Swelling behavior showed high swelling at low temperature (30 and 60 degrees C) as compared to high temperature (90 degrees C). PMID- 21971582 TI - Anti-proliferative effects of Chinese herb Cornus officinalis in a cell culture model for estrogen receptor-positive clinical breast cancer. AB - Selective estrogen receptor modulators and a combination of mechanistically distinct chemotherapeutic agents represent conventional therapeutic interventions for estrogen receptor-positive (ER+) clinical breast cancer. Long-term treatment with these agents is associated with acquired tumor resistance and other adverse side effects that impact on patient compliance. Herbal medicines are being widely used in complementary and alternative medicine. However, long-term safety and efficacy of the use of herbal medicines, as well as their interaction with conventional endocrine and chemotherapeutic drug regimens remain largely unknown. The present study utilized a human cell culture model for ER+ clinical breast cancer to examine the potential therapeutic efficacy of an aqueous extract prepared from the fruit of popular Chinese herb Cornus officinalis (CO), also known as Fructus cornii. The human mammary carcinoma-derived MCF-7 cell line represented the model. Status of anchorage-independent growth and cellular metabolism of 17beta-estradiol (E2) represented the quantitative end-point biomarkers for efficacy. MCF-7 cells adapted for growth in serum-depleted medium (0.7% serum, <1 nM E2) retained their endocrine responsiveness as evidenced by growth promotion by physiological levels of E2, and growth inhibition by the selective ER modulator tamoxifen at the clinically achievable concentrations. Treatment of MCF-7 cells with CO resulted in inhibition of E2-stimulated growth in a dose-dependent manner. Similarly, CO treatment also produced a dose dependent progressive reduction in the number of anchorage-independent colonies, indicating effective reduction of the carcinogenic risk. Treatment of MCF-7 cells with CO at a maximally effective cytostatic concentration resulted in a 5.1-fold increase in the formation of the anti-prolifertive E2 metabolite 2-hydoxyestrone (2-OHE1), a 63.6% decrease in the formation of the pro-mitogenic metabolite 16alpha-hydroxestrone (16-alphaOHE1) and a 9.1% decrease in the formation of mitogenically inert metabolite estrone (E3). These alterations led to a 14.5-fold increase in the 2-OHE1:16alpha-OHE1, and a 3.3-fold increase in the E3:16alpha OHE1 ratios. These data validate a rapid cell culture-based mechanistic approach to prioritize efficacious herbal medicinal products for long-term animal studies and future clinical trials on ER+ clinical breast cancer. PMID- 21971583 TI - Vincristine potentiates the anti-proliferative effect of an aurora kinase inhibitor, VE-465, in myeloid leukemia cells. AB - Aurora kinases play an essential role in the regulation of mitosis. The kinases are overexpressed in a variety of cancer cells and are involved in tumorgenesis. Although aurora kinase inhibitors are potential agents for treatment of leukemia, the establishment of efficacious combination therapies is an attractive approach for making good use of these agents. In this study, we examined the effects of a specific aurora kinase inhibitor, VE-465, in combination with various conventional anti-leukemia agents, including doxorubicin, daunorubicin, idarubicin, mitoxantron, cytosine arabinoside, vincristine and etoposide, on acute myeloid leukemia cell lines (HL60, U937, THP-1 and KY821), chronic myeloid leukemia cell lines (KCL22, K562 and KU812) and primary leukemia cells. We found that a combination of VE-465 and vincristine had a synergistic/additive inhibitory effect on the growth of leukemia cells. VE-465 initially increased G2/M-phase cells, followed by induction of sub-G1 cells. Vincristine enhanced this effect of VE-465. The combination of VE-465 and vincristine increased the levels of cleaved caspase 3, cleaved caspase 7, cleaved caspase 9, cleaved PARP and Phospho-Chk2, suggesting that the combination caused Chk2-mediated activation of the G2/M checkpoint, resulting in sequential induction of apoptosis. Interestingly, the combination markedly decreased the level of Phospho-ERK1/2, suggesting that the combination alters a network of cellular signaling pathways. In contrast, combinations of VE-465 and other agents showed no synergistic inhibitory effect but rather had an antagonistic effect. In conclusion, our results indicate the utility of the combination of VE-465 and vincristine as a potential therapy for myeloid leukemia. PMID- 21971585 TI - Disturbance and diversity at two spatial scales. AB - The spatial scale of disturbance is a factor potentially influencing the relationship between disturbance and diversity. There has been discussion on whether disturbances that affect local communities and create a mosaic of patches in different successional stages have the same effect on diversity as regional disturbances that affect the whole landscape. In a microcosm experiment with metacommunities of aquatic protists, we compared the effect of local and regional disturbances on the disturbance-diversity relationship. Local disturbances destroyed entire local communities of the metacommunity and required reimmigration from neighboring communities, while regional disturbances affected the whole metacommunity but left part of each local community intact. Both disturbance types led to a negative relationship between disturbance intensity and Shannon diversity. With strong local disturbance, this decrease in diversity was due to species loss, while strong regional disturbance had no effect on species richness but reduced the evenness of the community. Growth rate appeared to be the most important trait for survival after strong local disturbance and dominance after strong regional disturbance. The pattern of the disturbance diversity relationship was similar for both local and regional diversity. Although local disturbances at least temporally increased beta diversity by creating a mosaic of differently disturbed patches, this high dissimilarity did not result in regional diversity being increased relative to local diversity. The disturbance-diversity relationship was negative for both scales of diversity. The flat competitive hierarchy and absence of a trade-off between competition and colonization ability are a likely explanation for this pattern. PMID- 21971584 TI - Atmospheric change alters foliar quality of host trees and performance of two outbreak insect species. AB - This study examined the independent and interactive effects of elevated carbon dioxide (CO(2)) and ozone (O(3)) on the foliar quality of two deciduous trees species and the performance of two outbreak herbivore species. Trembling aspen (Populus tremuloides) and paper birch (Betula papyrifera) were grown at the Aspen FACE research site in northern Wisconsin, USA, under four combinations of ambient and elevated CO(2) and O(3). We measured the effects of elevated CO(2) and O(3) on aspen and birch phytochemistry and on gypsy moth (Lymantria dispar) and forest tent caterpillar (Malacosoma disstria) performance. Elevated CO(2) nominally affected foliar quality for both tree species. Elevated O(3) negatively affected aspen foliar quality, but only marginally influenced birch foliar quality. Elevated CO(2) slightly improved herbivore performance, while elevated O(3) decreased herbivore performance, and both responses were stronger on aspen than birch. Interestingly, elevated CO(2) largely offset decreased herbivore performance under elevated O(3). Nitrogen, lignin, and C:N were identified as having strong influences on herbivore performance when larvae were fed aspen, but no significant relationships were observed for insects fed birch. Our results support the notion that herbivore performance can be affected by atmospheric change through altered foliar quality, but how herbivores will respond will depend on interactions among CO(2), O(3), and tree species. An emergent finding from this study is that tree age and longevity of exposure to pollutants may influence the effects of elevated CO(2) and O(3) on plant-herbivore interactions, highlighting the need to continue long-term atmospheric change research. PMID- 21971586 TI - Terrestrial subsidies to lake food webs: an experimental approach. AB - Cross-ecosystem movements of material and energy are ubiquitous. Aquatic ecosystems typically receive material that also includes organic matter from the surrounding catchment. Terrestrial-derived (allochthonous) organic matter can enter aquatic ecosystems in dissolved or particulate form. Several studies have highlighted the importance of dissolved organic carbon to aquatic consumers, but less is known about allochthonous particulate organic carbon (POC). Similarly, most studies showing the effects of allochthonous organic carbon (OC) on aquatic consumers have investigated pelagic habitats; the effects of allochthonous OC on benthic communities are less well studied. Allochthonous inputs might further decrease primary production through light reduction, thereby potentially affecting autotrophic resource availability to consumers. Here, an enclosure experiment was carried out to test the importance of POC input and light availability on the resource use in a benthic food web of a clear-water lake. Corn starch (a C(4) plant) was used as a POC source due to its insoluble nature and its distinct carbon stable isotope value (delta(13)C). The starch carbon was closely dispersed over the bottom of the enclosures to study the fate of a POC source exclusively available to sediment biota. The addition of starch carbon resulted in a clear shift in the isotopic signature of surface-dwelling herbivorous and predatory invertebrates. Although the starch carbon was added solely to the sediment surface, the carbon originating from the starch reached zooplankton. We suggest that allochthonous POC can subsidize benthic food webs directly and can be further transferred to pelagic systems, thereby highlighting the importance of benthic pathways for pelagic habitats. PMID- 21971587 TI - A Th1 cytokine-enriched microenvironment enhances tumor killing by activated T cells armed with bispecific antibodies and inhibits the development of myeloid derived suppressor cells. AB - In this study, we investigated whether activated T cells (ATC) armed with bispecific antibodies (aATC) can inhibits tumor growth and MDSC development in a Th1 cytokine-enriched (IL-2 and IFN-gamma) microenvironment. Cytotoxicity mediated by aATC was significantly higher (P < 0.001) against breast cancer cell lines in the presence of Th1 cytokines as compared with control co-cultures. In the presence of aATC, CD33+ /CD11b+ /CD14- /HLA-DR- MDSC population was reduced significantly under both control (P < 0.03) and Th1-enriched (P < 0.036) culture conditions. Cytokine analysis in the culture supernatants showed high levels of MDSC suppressive chemokines CXCL9 and CXCL10 in Th1-enriched culture supernatants with highly significant increase (P < 0.001) in the presence of aATC. Interestingly, MDSC recovered from co-cultures without aATC showed potent ability to suppress activated T-cell-mediated cytotoxicity (P < 0.001), IFN-gamma production (P < 0.01) and T-cell proliferation (P < 0.05) compared to those recovered from aATC-containing co-cultures. These data suggest that aATC can mediate enhanced killing of tumor cells and may suppress MDSC and T(reg) differentiation, and presence of Th() cytokines potentiates aATC-induced suppression of MDSC, suggesting that Th1-enriching immunotherapy may be beneficial in cancer treatment. PMID- 21971588 TI - The small molecule TGF-beta signaling inhibitor SM16 synergizes with agonistic OX40 antibody to suppress established mammary tumors and reduce spontaneous metastasis. AB - Effective tumor immunotherapy may require not only activation of anti-tumor effector cells, but also abrogation of tumor-mediated immunosuppression. The cytokine TGF-beta, is frequently elevated in the tumor microenvironment and is a potent immunosuppressive agent and promoter of tumor metastasis. OX40 (CD134) is a member of the TNF-alpha receptor superfamily and ligation by agonistic antibody (anti-OX40) enhances effector function, expansion, and survival of activated T cells. In this study, we examined the therapeutic efficacy and anti-tumor immune response induced by the combination of a small molecule TGF-beta signaling inhibitor, SM16, plus anti-OX40 in the poorly immunogenic, highly metastatic, TGF beta-secreting 4T1 mammary tumor model. Our data show that SM16 and anti-OX40 mutually enhanced each other to elicit a potent anti-tumor effect against established primary tumors, with a 79% reduction in tumor size, a 95% reduction in the number of metastatic lung nodules, and a cure rate of 38%. This positive treatment outcome was associated with a 3.2-fold increase of tumor-infiltrating, activated CD8+ T cells, an overall accumulation of CD4+ and CD8+ T cells, and an increased tumor-specific effector T cell response. Complete abrogation of the therapeutic effect in vivo following depletion of CD4+ and CD8+ T cells suggests that the anti-tumor efficacy of SM16+ anti-OX40 therapy is T cell dependent. Mice that were cured of their tumors were able to reject tumor re-challenge and manifested a significant tumor-specific peripheral memory IFN-gamma response. Taken together, these data suggest that combining a TGF-beta signaling inhibitor with anti-OX40 is a viable approach for treating metastatic breast cancer. PMID- 21971589 TI - Cyclooxygenase inhibitors decrease the growth and induce regression of human esophageal adenocarcinoma xenografts in nude mice. AB - Cyclooxygenase (COX) inhibition has been shown to prevent the development of esophageal adenocarcinoma (EAC). However, the potential of this approach for treatment of established cancer has been poorly investigated. Our objective was to determine whether non-selective or selective inhibition of the COX pathway affects the growth of esophageal adenocarcinoma xenografts in nude mice. A human esophageal adenocarcinoma xenograft model was established by subcutaneous inoculation of OE33 cells in nude mice. Small tumor slices harvested from four OE33 xenografts were implanted in the flanks of new mice that were randomized to different treatments (6 animals per group): indomethacin (3 mg/kg/day), parecoxib (0.11 and 0.22 mg/kg/day) or a selective prostaglandin E2 receptor antagonist (AH 23848B, 1 mg/kg/day). For each treatment, a control group of 6 animals (vehicle) carrying xenografts from the same OE33 tumor was included. Tumor growth was measured twice a week. After 8 weeks mice were euthanized. Tumors were assessed by histological analysis, mRNA expression of COX isoenzymes, PGE2 receptors and PGE2 content. All OE33 tumors were poorly differentiated esophageal adenocarcinomas. Tumors expressed COX-2, EP1, EP2 and EP4 receptor mRNA. Treatment with parecoxib, higher dose or indomethacin significantly inhibited tumor growth. Furthermore, indomethacin induced tumor regression (74 vs 582% in control animals; p<0.01). However, AH-23848B or parecoxib low dose failed to affect tumor growth significantly. PGE2 content in tumors was significantly decreased by high-dose parecoxib and indomethacin. Indomethacin and parecoxib inhibit the growth of human esophageal adenocarcinoma xenografts in nude mice, which suggests a potential role for NSAIDs or selective COX-2 inhibitors for EAC chemotherapy. PMID- 21971591 TI - Clinical trials: The silent minority--unpublished data on cancer care. PMID- 21971590 TI - A comparison of satiety, glycemic index, and insulinemic index of wheat-derived soft pretzels with or without soy. AB - The consumption of nutrient-poor snack foods in Western diets is thought to be contributing to the increasing prevalence of obesity and diabetes. Soy offers unique potential to provide high quality protein, dietary fiber, and phytochemicals to snack foods to produce a more healthful nutritional profile. In this study, 27.3% of wheat flour was replaced with soy ingredients in a soft pretzel and evaluated for impact on satiety, glycemic index (GI), and insulinemic index (II). We first tested the soy pretzel for consumer acceptability by 51 untrained sensory panelists on a 9-point hedonic scale. Second, in a crossover trial, 20 healthy adults consumed soy and traditional pretzels (1000 kJ or 239 kcal each) after an overnight fast. They reported their levels of satiety on a 10 cm visual analog scale (VAS) for 2 h postprandially. Third, 12 healthy, non diabetic subjects consumed soy or traditional pretzels (50 +/- 2 g available carbohydrates) to determine the GI and II of both products. Blood glucose and insulin responses were monitored for 2 h after consumption and compared to a glucose reference. It was found that a consumer-acceptable soy soft pretzel had a lower mean (+/-SD) GI than its traditional counterpart: 39.1 (+/-20.4) for soy and 66.4 (+/-15.3) for wheat, (p = 0.002). However, soy addition did not statistically affect II (p = 0.15), or satiety (p = 0.91). In conclusion, a nutrient-dense soy pretzel formulation with 27.3% of wheat flour replaced by soy ingredients had attenuated postprandial glycemia without significantly affecting insulinemia or satiety in healthy adults. PMID- 21971592 TI - Chemotherapy: Hodgkin lymphoma--absence of evidence not evidence of absence! PMID- 21971595 TI - Parameters from the community of leaf-litter frogs from Estacao Ecologica Estadual Paraiso, Guapimirim, Rio de Janeiro State, southeastern Brazil. AB - We studied the leaf-litter frog community of Estacao Ecologica Estadual Paraiso, in Guapimirim, Rio de Janeiro State, southeastern Brazil. Herein we combined three sampling methods (large plots, visual encounter surveys and pit-fall traps) to present data on species composition, richness, relative abundance and densities. The local assemblage of frogs associated to the leaf-litter was composed by 14 species, belonging to nine families. Haddadus binotatus, a direct developing frog, was the most abundant species in the community. The estimated density of the local leaf-litter frog assemblage based on plot sampling was 4.3 frogs/100 m(2). Haddadus binotatus had the highest density (1.1 ind/100 m(2)). Frogs were predominantly found at night. Thoropa miliaris had the largest values of SVL (39.0 +/- 10.3 mm), whereas the smallest species were Euparkerella brasiliensis (16.7 +/- 2.2 mm) and E. cochranae (16.0 +/- 2.7 mm). Rhinella ornata had the highest mean body mass (12.1 +/- 7.5 g), and E. cochranae the lowest (0.4 +/- 0.2 g). The overall frog mass was 938.6 g/ha. Our data support that higher densities of leaf-litter frogs tend to occur in the Neotropical region compared to the OldWorld tropics, tending to be higher in Central America than in South America. PMID- 21971596 TI - Growth of immature Chironomus calligraphus in laboratory conditions. AB - Chironomidae larvae are important macroinvertebrates in limnic environments, but little knowledge exists about their biometrics development characteristics. This study aims to describe the immature Chironomus calligraphus Goeldi, 1905 under laboratory conditions by the accomplishment of thirteen egg masses from eggs eclosion to adults emergency, at controlled room temperature (25oC) and photoperiod (12-12h). Larvae were feed ad libitum with "Alcon Basic - MEP 200 Complex" fish food and commercial dehydrated Spirulina. The postures had a mean length of 9 +/- 1 mm (n = 13) and 348 +/- 66 eggs. The brownish colored eggs with elliptical shape had length of 160.3 +/- 17.7 um (n = 130), being arranged as an organized string in a pseudo spiral form. The time duration from the first to the four instars were three, four, four and eight days, and the average length of a cephalic capsule to each one of the instars (66.3 +/- 12.3 um, 102.9 +/- 22.1 um, 159 +/- 24.6 um, 249.2 +/- 29.7 um, n = 456) were significantly different (ANOVA, p < 0.001). The Dyar?s Rule showed a constant growth rate, r = 1.5. Our results demonstrated that C. calligraphus is a species with short life cycle, low mortality rate, food adaptability, fast larval growth and easily maintained at laboratory, factors that allowed the use of this native species as a tool for ecotoxicological tests. PMID- 21971597 TI - Phenotypic stability of hybrids of Galia melon in Rio Grande do Norte state, Brazil. AB - The objectives of this study were to determine the importance of simple and complex components of the interaction genotype * environment and to evaluate the adaptability and stability of Galia melon hybrids. Nine hybrids were tested in twelve environments of Rio Grande Norte State from 2000 to 2001. The experiments were carried out in a randomized complete block design with three replications. The statistical methods of Toler and Burrows, Wricke and AMMI (Additive Main effect and Multiplicative Interaction) were used to study the adaptability and stability. The complex component is responsible for most of the genotype * environment interaction for the yield and content of solids soluble of fruits. The environments associated with Mossoro and Assu municipalities are the most suitable to evaluate melon hybrids in the state. The hybrid DRG 1537 was the most likely to be grown in the Agro-industrial Complex Mossoro-Assu due to its stability, high productivity and high content of soluble solids. PMID- 21971599 TI - Synthesis and spectrophotometric P(H) sensing applications of poly-2-[4 (diethylaminophenyl)imino]-5-nitro-phenol and its Schiff base monomer for two different P(H) ranges. AB - Poly-2-[4-(diethylaminophenyl)imino]-5-nitro-phenol (PEAPINP) and 2-[4 (diethylaminophenyl)imino]-5-nitro-phenol (EAPINP) were prepared as new pH sensors. Spectrophotometric and spectrofluorometric response of the novel sensors in various p(H) values were investigated. EAPINP has the ability to respond linearly at alkaline P(H) values, 8 to 9, and can be utilized in absorption and wavelength radiometric methods. PEAPINP has the ability to respond linearly at lower pH values, 6 to 7, and can be used as an alternative pH sensor in this range. The new sensors are yellow-colored in acidic and neutral media and red colored in alkaline P(H)s. With their colorimetric responses at different pH ranges EAPINP and PEAPINP can be used to develop color-tunable P(H) sensors. PMID- 21971601 TI - From the editors' desk: peer review now and in the future. PMID- 21971600 TI - Relationship of health literacy to intentional and unintentional non-adherence of hospital discharge medications. AB - BACKGROUND: Inadequate health literacy is prevalent among seniors and is associated with poor health outcomes. At hospital discharge, medications are frequently changed and patients are informed of these changes via their discharge instructions. OBJECTIVES: Explore the association between health literacy and medication discrepancies 48 hours after hospital discharge and determine the causes of discharge medication discrepancies. DESIGN: Face-to-face surveys assessing health literacy at hospital discharge using the short form of the Test of Functional Health Literacy in Adults (sTOFHLA). We obtained the medication lists from the written discharge instructions. At 48 hrs post-discharge, we phoned subjects to assess their current medication regimen, any medication discrepancies, and the causes of the discrepancies. PARTICIPANTS: Two hundred and fifty-four community-dwelling seniors >= 70 years, admitted to acute medicine services for >24 hours at an urban hospital. RESULTS: Of 254 seniors [mean age 79.3 yrs, 53.1% female], 142 (56%) had a medication discrepancy between their discharge instructions and their actual home medication use 48 hrs after discharge. Subjects with inadequate and marginal health literacy were significantly more likely to have unintentional non-adherence--meaning the subject did not understand how to take the medication [inadequate health literacy 47.7% vs. marginal 31.8% vs. adequate 20.5% p = 0.002]. Conversely, those with adequate health literacy were significantly more likely to have intentional non adherence--meaning the subject understood the instructions but chose not to follow them as a reason for the medications discrepancy compared with marginal and inadequate health literacy [adequate 73.3% vs. marginal 11.1% vs. inadequate 15.6%, p < 0.001]. Another common cause of discrepancies was inaccurate discharge instructions (39.3%). CONCLUSION: Seniors with adequate health literacy are more inclined to purposefully not adhere to their discharge instructions. Seniors with inadequate health literacy are more likely to err due to misunderstanding their discharge instructions. Together, these results may explain why previous studies have shown a lack of association between health literacy and overall medication discrepancies. PMID- 21971602 TI - Evidence, values, guidelines and rational decision-making. AB - Medical decision-making involves choices, which can lead to benefits or to harms. Most benefits and harms may or may not occur, and can be minor or major when they do. Medical research, especially randomized controlled trials, provides estimates of chance of occurrence and magnitude of event. Because there is no universally accepted method for weighing harms against benefits, and because the ethical principle of autonomy mandates informed choice by patient, medical decision making is inherently an individualized process. It follows that the practice of aiming for universal implementation of standardized guidelines is irrational and unethical. Irrational because the possibility of benefits is implicitly valued more than the possibility of comparable harms, and unethical because guidelines remove decision making from the patient and give it instead to a physician, committee or health care system. This essay considers the cases of cancer screening and diabetes management, where guidelines often advocate universal implementation, without regard to informed choice and individual decision-making. PMID- 21971603 TI - Association between promoter polymorphisms of the LIFR gene and schizophrenia with persecutory delusion in a Korean population. AB - Schizophrenia has been associated with an imbalance in inflammatory cytokines. Leukemia inhibitory factor receptor alpha (LIFR) is an integral component of the glycoprotein 130-LIFR signaling complex, which participates in signal transduction by members of the interleukin (IL)-6 cytokine family. The aim of this study was to investigate whether genetic polymorphisms of the LIFR gene are associated with schizophrenia in the Korean population. We also explored possible associations between the polymorphisms and the clinical symptoms of schizophrenia. We selected three single nucleotide polymorphisms (SNPs) (rs2071237 -200C/G, rs2071236 -254C/T and rs6862038 -962A/G) on the promoter region of the LIFR gene and recruited 204 schizophrenia patients and 367 control subjects from the Korean population. All patients were evaluated according to the Operational Criteria Checklist for Psychotic Illness. SNP genotyping was performed by direct sequencing. An analysis of multiple logistic regression models (co-dominant 1, co-dominant 2, dominant, recessive and overdominant) was performed to evaluate odds ratios (ORs), 95% confidence intervals (CIs) and p values. No significant difference was revealed between schizophrenia patients and controls. However, a significant association was detected between the LIFR gene polymorphisms and schizophrenia patients with persecutory delusion (rs2071236, OR=2.18, 95% CI=1.20-3.94, P=0.009 in the overdominant model; rs6862038, OR=2.08, 95% CI=1.16-3.74, P=0.013 in the overdominant model). The present study suggests that the LIFR gene may be related to schizophrenia with persecutory delusion in the Korean population. PMID- 21971604 TI - Treatment of autonomously functioning thyroid nodules at a single institution: radioiodine therapy, surgery, and ethanol injection therapy. AB - OBJECTIVE: The purpose of this study was to clarify the efficacy of radioiodine (RI) therapy in Japanese patients with autonomously functioning thyroid nodules (AFTNs). METHODS: We performed a retrospective analysis to assess the management of AFTN patients. Thyroid lobectomy was performed to treat toxic adenoma (TA) patients, and total thyroidectomy to treat toxic multinodular goiter (TMNG) patients. RI therapy was administered in the form of a single dose (500 MBq) of isotope in the outpatient clinic. Percutaneous ethanol injection therapy (PEIT) was performed under ultrasound guidance. RESULTS: Of the total 205 patients, consisting of 159 TA and 46 TMNG patients, 99 underwent surgery, 50 received RI therapy, and 56 received PEIT. Remission of thyrotoxicosis was achieved in all of the patients who were treated surgically. Hypothyroidism was documented in six of the 72 patients who were treated surgically other than by total thyroidectomy. Remission of thyrotoxicosis was observed in 43 of the 50 patients who were treated by RI therapy. Nine TA patients developed hypothyroidism during the follow-up period after RI therapy. Several PEIT sessions were required to achieve a remission of thyrotoxicosis. Remission of thyrotoxicosis was achieved in 29 of the 56 patients treated by PEIT, and thyrotoxicosis recurred in 17 these 56 patients. CONCLUSION: Surgery is the treatment of choice for large nodules and nodules that are resistant to other treatments, because it allows prompt control of thyrotoxicosis. RI therapy is a safe and effective means of controlling thyrotoxicosis in AFTN patients. We conclude that RI therapy is the treatment of choice for definitive treatment of AFTN patients who do not have local compression symptoms. PMID- 21971605 TI - Diagnostic accuracy of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in differentiated thyroid cancer patients with elevated thyroglobulin and negative (131)I whole body scan: evaluation by thyroglobulin level. AB - BACKGROUND: To evaluate the diagnostic accuracy of (18)F-FDG PET/CT in detection of recurrent differentiated thyroid cancer (DTC) in patients with elevated stimulated thyroglobulin (Tg) or anti-Tg antibody (Ab) levels, and negative (131)I whole body scan according to the Tg level. METHODS: PET/CT images of well DTC patients who had total thyroidectomy and radioiodine ablation were included. Patients showing elevated Tg titer (>=2.0 ng/ml after TSH stimulation) or elevated anti-Tg titer (>=70.0 IU/ml) while diagnostic radioiodine scan was negative were enrolled. PET/CT was classified as positive or negative on the basis of visual interpretation. The maximum standard uptake values (SUVmax) of the suspected lesions on PET/CT were also recorded. The PET/CT findings were compared with histological or clinical follow-up results based on other imaging modalities and serum Tg/anti-Tg Ab titers. The diagnostic performance of PET/CT was compared among 4 subgroups according to the Tg level [2 ng/ml <= stimulated Tg (sTg) < 5 ng/ml, 5 ng/ml <= sTg < 10 ng/ml, 10 ng/ml <= sTg < 20 ng/ml, and >=20 ng/ml]. RESULTS: A total of 68 PET/CT images from 60 patients were included, and histological confirmations were available in 32 images. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of PET/CT were 69.4, 66.7, 69.1, 95.6, and 17.4%, respectively. There were 3 PET/CT cases with high anti-Tg Ab level, and low (<2 ng/ml) Tg level, and all 3 were positive of recurrence. The mean SUVmax of the suspected lesions on PET/CT was 2.9 +/- 4.5 (range 1.3-29.7). The sensitivity of PET/CT according to Tg levels was 28.6% when Tg was between 2 and 5, 57.1% between 5 and 10, 60.0% between 10 and 20, and 85.7% when Tg was equal to or greater than 20 ng/ml sub-groups, respectively. CONCLUSION: Diagnostic accuracy of FDG PET in radioiodine negative thyroid cancer may vary depending on serum Tg levels at imaging. (18)F-FDG PET/CT is useful in detection and localization of recurrent thyroid cancer in patients with negative diagnostic radioiodine scan despite elevated Tg greater than 20 ng/ml or high anti-Tg Ab titers. In contrast, PET/CT provides little additional information when the Tg is less than 5 ng/ml. PMID- 21971606 TI - "Identify-to-reject": a specific strategy to avoid false memories in the DRM paradigm. AB - Previous research using the Deese-Roediger-McDermott (DRM) paradigm has shown that lists of associates in which the critical words were easily identified as the themes of the lists produce lower levels of false memories in adults. In an attempt to analyze whether this effect is due to the application of a specific memory-editing process (the identify-to-reject strategy), two experiments manipulated variables that are likely to disrupt this strategy either at encoding or at retrieval. In Experiment 1, lists were presented at a very fast presentation rate to reduce the possibility of identifying the missing critical word as the theme of the list, and in Experiment 2, participants were pressed to give yes/no recognition answers within a very short time. The results showed that both of these manipulations disrupted the identifiability effect, indicating that the identify-to-reject strategy and theme identifiability play a major role in the rejection of false memories in the DRM paradigm. PMID- 21971607 TI - Use of sugarcane molasses "B" as an alternative for ethanol production with wild type yeast Saccharomyces cerevisiae ITV-01 at high sugar concentrations. AB - Molasses "B" is a rich co-product of the sugarcane process. It is obtained from the second step of crystallization and is richer in fermentable sugars (50-65%) than the final molasses, with a lower non-sugar solid content (18-33%); this co product also contains good vitamin and mineral levels. The use of molasses "B" for ethanol production could be a good option for the sugarcane industry when cane sugar prices diminish in the market. In a complex medium like molasses, osmotolerance is a desirable characteristic for ethanol producing strains. The aim of this work was to evaluate the use of molasses "B" for ethanol production using Saccharomyces cerevisiae ITV-01 (a wild-type yeast isolated from sugarcane molasses) using different initial sugar concentrations (70-291 g L(-1)), two inoculum sizes and the addition of nutrients such as yeast extract, urea, and ammonium sulphate to the culture medium. The results obtained showed that the strain was able to grow at 291 g L(-1) total sugars in molasses "B" medium; the addition of nutrients to the culture medium did not produce a statistically significant difference. This yeast exhibits high osmotolerance in this medium, producing high ethanol yields (0.41 g g(-1)). The best conditions for ethanol production were 220 g L(-1) initial total sugars in molasses "B" medium, pH 5.5, using an inoculum size of 6 * 10(6) cell mL(-1); ethanol production was 85 g L( 1), productivity 3.8 g L(-1 )h(-1) with 90% preserved cell viability. PMID- 21971608 TI - Effects of glutamate decarboxylase and gamma-aminobutyric acid (GABA) transporter on the bioconversion of GABA in engineered Escherichia coli. AB - Gamma-aminobutyric acid (GABA) is a non-essential amino acid and a precursor of pyrrolidone, a monomer of nylon 4. GABA can be biosynthesized through the decarboxylation of L: -glutamate by glutamate decarboxylase. In this study, the effects of glutamate decarboxylase (gadA, gadB), glutamate/GABA antiporter (gadC) and GABA aminotransferase (gabT) on GABA production were investigated in Escherichia coli. Glutamate decarboxylase was overexpressed alone or with the glutamate/GABA antiporter to enhance GABA synthesis. GABA aminotransferase, which redirects GABA into the TCA cycle, was knock-out mutated. When gadB and gadC were co-overexpressed in the gabT mutant strain, a final GABA concentration of 5.46 g/l was obtained from 10 g/l of monosodium glutamate (MSG), which corresponded to a GABA yield of 89.5%. PMID- 21971609 TI - Diagnostic value of multiple biomarker panel for prediction of significant fibrosis in chronic hepatitis C. AB - OBJECTIVES: Whether new biomarkers contribute significantly to the existing, simple noninvasive test (comprising of routine laboratory parameters such as the AST to platelet ratio index (APRI)) for predicting liver fibrosis remains unknown. METHODS: We measured 7 biomarkers in 91 patients with chronic hepatitis C (CHC): haptoglobin, apolipoprotein A1, alpha2-macroglobulin, hyaluronic acid, type III procollagenic peptide, matrix metalloproteinase-2, and tissue inhibitor of metalloproteinase-1. RESULTS: The "multibiomarker" score (based on regression coefficients of significant biomarkers) is an independent predictive factor for significant fibrosis [APRI-adjusted odds ratio, 2.41 (95% CI, 1.28 to 4.55)]. However, the incorporation of the multibiomarker score into the APRI resulted in only a small diagnostic improvement [0.83 (95% CI, 0.74 to 0.92) vs. 0.79 (0.69 to 0.89); p=0.19]. CONCLUSIONS: For assessing significant fibrosis in individual CHC patients, the 7 contemporary biomarkers that we studied add only modestly to the readily available, simple noninvasive index. PMID- 21971610 TI - Mesenchymal stem cells promote tumor engraftment and metastatic colonization in rat osteosarcoma model. AB - Although mesenchymal stem cells (MSCs) are considered to be the cells of origin for most sarcomas, the role of MSCs as a source of tumor stroma is not fully understood in this tumor type. The current study investigated whether MSCs affect the tumor growth and metastatic ability in rat osteosarcoma model. Results from subcutaneous co-implantation of rat osteosarcoma COS1NR cells, established in our laboratory, with rat MSCs isolated from femur bone marrow showed that the incidence of tumor formation and tumor growth rate was higher until 5 weeks compared to COS1NR cell inoculation alone. However, no difference was observed in tumor growth afterwards and in the number of metastatic nodules at 9 weeks (0.75 vs. 1.2). Intravenous MSC injection at weeks 3 and 5 after subcutaneous inoculation of COS1NR cells significantly increased the number of lung nodules in the group with MSC injection compared to the group without MSC injection (17.33 vs. 2.0), while no difference was observed in subcutaneous tumor growth between those groups. Pathway analysis from gene expression profile identified that genes involved in focal adhesion, cytokine-cytokine receptor and extracellular matrix receptor pathways such as CAMs (ICAM and VCAM)-integrins were highly expressed in MSCs, possibly participating in the tumor progression of osteosarcoma. These results suggest that MSCs could provide a source of microenvironments for osteosarcoma cells, and might enhance the ability of settlement and colonization which lead to early onset of growth and metastasis, possibly through their activated pathways interaction. PMID- 21971613 TI - [Acute lymphatic leukemia in childhood]. PMID- 21971612 TI - Postnatal morphine administration alters hippocampal development in rats. AB - Morphine is frequently used as an analgesic and sedative in preterm infants. Adult rats exposed to morphine have an altered hippocampal neurochemical profile and decreased neurogenesis in the dentate gyrus of the hippocampus. To evaluate whether neonatal rats are similarly affected, rat pups were injected twice daily with 2 mg/kg morphine or normal saline from postnatal days 3 to 7. On postnatal day 8, the hippocampal neurochemical profile was determined using in vivo (1)H NMR spectroscopy. The mRNA and protein concentrations of specific analytes were measured in hippocampus, and cell division in dentate gyrus was assessed using bromodeoxyuridine. The concentrations of gamma-aminobutyric acid (GABA), taurine, and myo-insotol were decreased, whereas concentrations of glutathione, phosphoethanolamine, and choline-containing compounds were increased in morphine exposed rats relative to control rats. Morphine decreased glutamic acid decarboxylase enzyme levels and myelin basic protein mRNA expression in the hippocampus. Bromodeoxyuridine labeling in the dentate gyrus was decreased by 60 70% in morphine-exposed rats. These results suggest that recurrent morphine administration during brain development alters hippocampal structure. PMID- 21971616 TI - [Intermittent or persistent rhinitis in children and adolescents with Asthma: "the Swiss LARA paediatrics survey"]. AB - Asthma and allergic rhinitis are chronic inflammatory airway diseases which often occur concomitantly. The objective of the LARA program was to identify the comorbidities and characteristics of asthma (A), intermittent or persistent rhinitis (IPR) and physician defined atopic dermatitis (AD) in 6- to 16-year old asthmatic Swiss children and adolescents. Overall, 126 general practitioners and paediatricians collected the data of 670 asthmatics. Approximately one third of the asthmatic children in Switzerland had well-controlled asthma. Almost two thirds of these asthmatics suffered from concomitant IPR. The latter presented with significantly less symptoms while the treatment rates with inhaled corticosteroids (approximately 90%) and leukotriene-receptorantagonists (approximately 50%) were comparable. However, there were almost twice as many passive smokers in the less well-controlled group. The prevalence of AD was similar in both groups. IPR and AD may play an important role as risk factors in the future development of asthma. PMID- 21971617 TI - [Sport practice and arrhythmias]. AB - Regular exercise decreases the risk of coronary artery disease by controlling risk factors. On the other hand, vigorous exertion increases the risk of sudden cardiac death in subjects with pre-existing cardiac diseases. Long term endurance sport practice may increase the incidence of atrial fibrillation, atrial flutter and sinus node dysfunction in otherwise healthy subjects. PMID- 21971618 TI - [Erythropoietinin oncologic therapy -- what so we know about the risks?]. AB - Erythropoietin is a glycoprotein predominantly produced in the kidney. It is an essential regulator of erythropoiesis in the bone marrow. Although cancer associated anemia is caused by multiple factors, recombinant erythropoietin (rhuEpo) was widely used to treat and prevent this condition. Several clinical studies showed that the use of rhuEpo results in an efficient reduction of red blood cell transfusions in cancer-associated anemia. However, over the past twenty years, Epo and its receptor EpoR were found to be expressed also outside the hematopoietic system and in malignant tumors. This led to a discussion concerning potential risks associated with the application of erythropoiesis stimulating agents in oncology. PMID- 21971619 TI - [Cholesteatoma]. PMID- 21971620 TI - [What is the status of steroids in the treatment of infants with bronchiolitis?]. PMID- 21971621 TI - [Not Available]. PMID- 21971622 TI - [Not Available]. PMID- 21971627 TI - An education initiative concerning lead in an Arkansas community: results from pre- and post-surveys. AB - The Arkansas People Participating in Lead Education (APPLE) Program is a collaborative effort between six Arkansas state, national and community organizations to provide lead awareness, training, and municipal legislation to needy communities in Arkansas. Under this program, APPLE organized and hosted well-designed, hands-on, and effective "call to action" lead awareness workshops for parents and community members in 10 needy communities over a 2 year period. Pre- and post-surveys were given to community members to access knowledge, attitudes and effectiveness of lead workshop activities, with demographic and another 13 and 11 questions on pre- and post-surveys, respectively. There were 709 adult attendees across the 10 workshop (Many children also attended.), with 460 completing pre-surveys, and 199 completed post-survey. Post-surveys were limited to four cities. The majority of those who completed surveys were African American, reported as 78% on pre-surveys, with the majority also being parents (61%) and females. Although, 71% reported knowing that lead paint was bad for their health, more than 60% reported knowing little about lead exposure, and another 25% did not know the age of their residence. On the post-surveys, the majority of respondents found the workshop to be pleasant and informative (98%), while 45% had changed something in their lives to prevent lead exposure for a child and another 53% planned to make a change to prevent lead exposure for a child. PMID- 21971628 TI - Diabetes prevention education program for community health care workers in Thailand. AB - To evaluate the effects of a 4-month training program on the knowledge of CHCWs. CHCWs from 69 communities in Chiang Mai province in Thailand were assigned to the intervention group (IG, n=35) or control group (CG, n=34). All CHCWs were assessed for knowledge at baseline and at 4-months. The intervention group received a training program of 16 sessions of 2.5 h each within a 4-month period. A mix of classroom and E-learning approaches was used. All CHCWs were assessed for knowledge at baseline, 4-month, and follow-up at 8-month. Assessment was based on a pretested examination addressing understanding of nutritional terms and recommendations, knowledge of food sources related to diabetes prevention and diet-disease associations. Overall, the knowledge at baseline of both groups was not significantly different and all CHCWs scored lower than the 70% (mean (SD), 56.5% (6.26) for IG and 54.9% (6.98) for CG). After 4-month, CHCWs in the IG demonstrated improvement in total scores from baseline to 75.5% (6.01), P< .001 and relative to the CG 57.4% (5.59), P< .001. The follow up phase at 8-month, IG were higher in total scores than CG (71.3% (7.36) and 62.4% (6.81), P< .001). The diabetes prevention education program was effective in improving CHCWs' health knowledge relevant to diabetes prevention. The innovative learning model has potential to expand chronic disease prevention training of CHCWs to other parts of Thailand. PMID- 21971629 TI - Carbohydrate content of post-operative diet influences the effect of vertical sleeve gastrectomy on body weight reduction in obese rats. AB - BACKGROUND: Vertical sleeve gastrectomy (VSG) effectively reduces body weight (BW) in obese rats and humans. However, post-surgical weight regain is frequently observed in subjects after VSG, but the underlying reasons remain poorly understood. We therefore investigated if post-surgical consumption of different diets can affect the outcome of VSG. METHODS: VSG or sham operation was performed in Long-Evans rats with diet-induced obesity (n = 37). After post-surgical recovery, rats were fed ad libitum either with standard chow (CH), high-fat (HF) or low-carbohydrate, high-fat (LCHF) diets. BW and food intake were measured every second day; serum leptin, cholesterol, HDL cholesterol, and triglycerides were analyzed 4 weeks after surgery. Energy expenditure and locomotor activity were determined by a combined indirect calorimetry system, lean and fat mass by nuclear magnetic resonance. RESULTS: After 4 weeks, BW gain, fat mass, and leptin were lower in VSG rats when compared to sham controls (p < 0.05). Energy expenditure and locomotor activity were not affected by VSG indicating that weight reduction derives from the significantly lower cumulative 4-week energy intake in VSG compared to sham. Sham rats fed LCHF consumed the most energy, followed by rats fed HF. In contrast, after VSG cumulative energy intake was highest in rats fed HF, but not different between CH and LCHF. Consistently, post surgical BW and fat mass regain were highest in the HF-VSG group. Lipid profiles were improved by VSG but not differentially affected by diets. CONCLUSION: In conclusion, consumption of a HF diet but not the more energy-dense LCHF diet reduced the effectiveness of VSG in rats. PMID- 21971630 TI - Roux limb volvulus in laparoscopic Roux-en-Y gastric bypass due to Roux limb stabilization suture: case series. AB - BACKGROUND: Complications after laparoscopic Roux-en-Y gastric bypass surgery may be related to the type of surgical technique employed. One technique, the placement of a Roux limb stabilization suture, presumably prevents kink at the gastrojejunal anastomosis. However, it can have an adverse effect and we studied a series of cases presenting with intestinal obstruction secondary to this stitch. METHODS: A retrospective review of a prospectively collected database of laparoscopic Roux-en-Y gastric bypass cases who had reoperations for Roux limb volvulus was performed at a single bariatric center by a single surgeon. RESULTS: Out of 199 patients who underwent laparoscopic Roux en Y gastric bypass with placement of Roux limb stabilization suture, 4 patients (2.01%) presented with Roux limb volvulus postoperatively. BMI was 45.35 +/- 2.95. The postoperative time to presentation was 11 +/- 10.6 months. All four patients required surgical exploration to reduce the volvulus. In all cases, the Roux limb volvulus was directly attributable to the presence of the stabilization suture. In subsequent 250 cases where this suture was eliminated, there was no volvulus of Roux limb seen. CONCLUSIONS: The use of a stabilization suture can result in volvulus of the Roux limb causing intestinal obstruction and this complication can be prevented by avoiding this suture. PMID- 21971631 TI - Inhibition of L-type calcium current by tramadol and enantiomers in cardiac myocytes from rats. AB - BACKGROUND: Tramadol is a centrally acting analgesic, whose mechanism of action involves opioid-receptor activation. Previously, we have shown that tramadol and its enantiomers had a negative inotropic effect on the papillary muscle in which the (+)-enantiomer is more potent than (-)- and (+/-)-tramadol. OBJECTIVE: In this study, we investigated the effects of tramadol and its enantiomers on L-type calcium current (ICa-L). METHODS: The experiments were carried out in isolated Wistar rat ventricular myocytes by using the whole cell patch clamp technique. RESULTS: Tramadol (200 uM) reduced the peak amplitude of ICa-L at potentials from 0 to +50 mV. At 0 mV, I(Ca-L) was reduced by 33.7 +/- 7.2%. (+)- and (-)-tramadol (200 uM) produced a similar inhibition of ICa-L, in which the peak amplitude was reduced by 64.4 +/- 2.8% and 68.9 +/- 5.8%, respectively at 0 mV (p > 0.05). Tramadol, (+)- and (-)-tramadol shifted the steady-state inactivation of ICa-L to more negative membrane potentials. Also, tramadol and (+)-tramadol markedly shifted the time-dependent recovery curve of I(Ca-L) to the right and slowed down the recovery of I(Ca-L) from inactivation. The time constant was increased from 175.6 +/- 18.6 to 305.0 +/- 32.9 ms (p < 0.01) for tramadol and from 248.1 +/- 28.1 ms to 359.0 +/- 23.8 ms (p < 0.05) for (+)-tramadol. The agonist of u-opioid receptor DAMGO had no effect on the I(Ca-L). CONCLUSION: The inhibition of ICa-L induced by tramadol and its enantiomers was unrelated to the activation of opioid receptors and could explain, at least in part, their negative cardiac inotropic effect. PMID- 21971632 TI - Effects of angiotensin-I and ischemia on functional recovery in isolated hearts. AB - BACKGROUND: Cardiac arrest resuscitation can present myocardial dysfunction determined by ischemic time, and inhibition of the angiotensin-converting enzyme (ACE) can reduce cardiac dysfunction during reperfusion. OBJECTIVE: To investigate the effects of angiotensin-I and different periods of ischemia on functional recovery in isolated rat hearts. METHODS: Isolated hearts from Wistar rats (n=45; 250-300 g) were submitted to different periods of global ischemia (20, 25 or 30 min) and reperfused (30 min) with Krebs-Henseleit buffer alone or with the addition of 400 nmol/L angiotensin-I, or 400 nmol/L angiotensin-I + 100 MUmol/L captopril along the reperfusion period. RESULTS: The maximal positive derivative of pressure (+dP/dt(max)) and rate-pressure product were reduced in hearts exposed to 25 min ischemia (~73%) and 30 min ischemia (~80%) vs. 20 min ischemia. Left ventricular end-diastolic pressure (LVEDP) and perfusion pressure (PP) were increased in hearts exposed to 25 min ischemia (5.5 and 1.08 fold, respectively) and 30 min ischemia (6 and 1.10 fold, respectively) vs. 20 min ischemia. Angiotensin-I caused a decrease in +dP/dt(max) and rate-pressure product (~85-94%) in all ischemic periods and an increase in LVEDP and PP (6.9 and 1.25 fold, respectively) only at 20 min ischemia. Captopril was able to partially or completely reverse the effects of angiotensin-I on functional recovery in 20 min and 25 min ischemia. CONCLUSION: These data suggest that angiotensin-II directly or indirectly participates in the post-ischemic damage, and the ability of an ACE inhibitor to attenuate this damage depends on ischemic time. PMID- 21971633 TI - Calcium score in the evaluation of atherosclerosis in patients with HIV/AIDS. AB - BACKGROUND: Antiretroviral therapy has dramatically increased life expectancy in patients with HIV/AIDS although atherosclerosis has been associated with long standing therapy. OBJECTIVE: To investigate the prevalence of atherosclerosis in patients with AIDS undergoing antiretroviral therapy and the influence of different schemes and duration of treatment. METHODS: HIV/AIDS patients were approached during routine consultations. Those who had been on antiretroviral therapy for at least two years had their blood collected for analysis of lipid profile and fasting glycemia and underwent cardiac CT for quantification of calcium score within six days at the most. Atherosclerosis was defined as calcium score greater than zero (CAC > 0). Traditional risk factors, metabolic syndrome and Framingham score were analyzed. RESULTS: Fifty-three patients performed cardiac CT. Twenty-seven (50.94%) were male, mean age 43.4 years; 20.00% had hypertension, 3.77% diabetes, 67.92% hypercholesterolemia, 37.74% hypertriglyceridemia and 47.17% low HDL. Thirteen (24.53%) met criteria for metabolic syndrome and 96.23% were classified in Framingham score as "low risk." Ten patients (18.87%) were smokers. Mean duration of antiretroviral treatment was 58.98 months. Coronary atherosclerosis occurred in 11 (20.75%) patients. Duration of antiretroviral therapy was not related to atherosclerosis (p = 0.41) and there were no significant differences between different antiretroviral regimens (p = 0.71). Among traditional risk factors, smoking (OR = 27.20; p = 0.023) and age (OR = 20.59; p = 0.033) were significant in the presence of atherosclerosis. There was a trend towards a positive association of atherosclerosis with hypercholesterolemia (OR = 8.30; p = 0.0668). CONCLUSION: Factors associated with atherosclerosis were age, smoking and hypercholesterolemia. Duration and type of antiretroviral therapy had no influence on the prevalence of atherosclerosis. PMID- 21971634 TI - Association of different anthropometric measures and indices with coronary atherosclerotic burden. AB - BACKGROUND: The association between anthropometric parameters and atherosclerotic burden is not well established and few studies have addressed this issue. OBJECTIVE: To evaluate the association of different anthropometric parameters with the coronary atherosclerotic burden. METHODS: Adult patients undergoing coronary angiography were enrolled in the study. Sociodemographic characteristics and cardiovascular risk factors were collected through a standardized questionnaire. Weight, height, waist circumference (WC), abdominal circumference (AbC), hip circumference (HC) and neck circumference (NC) were measured and body mass index (BMI), waist-hip ratio (WHR), abdominal circumference-hip ratio (AbCHR) and waist-height ratio (WHtR) were calculated. The atherosclerotic burden at the coronary angiography was measured through Friesinger score (FS). Significant atherosclerosis was considered when FS >= 5. RESULTS: The sample consisted of 337 patients, of whom 213 were men (63.2%). The mean age was 60.1 +/ 10 years. Only WHR (r = 0.159 and p = 0.003) showed a significant linear correlation with the coronary atherosclerotic burden as measured by FS. When the sample was stratified by gender, we found a significant correlation between women's AbCHR (r = 0.238 and p = 0.008) and WHR (r = 0.198 and p = 0.028) with FS. Men showed no correlation between anthropometric parameters and FS. After adjusting for gender, age, hypertension, smoking and DM, no anthropometric parameter was associated with coronary atherosclerotic burden as measured by FS in the total sample or when separated by gender. CONCLUSION: No anthropometric parameter was an independent risk factor for coronary atherosclerotic burden. PMID- 21971635 TI - Preoperative C-reactive protein predicts respiratory infection after coronary artery bypass graft surgery. AB - BACKGROUND: Increased levels of high-sensitive C-reactive protein (hsCRP) in the preoperative evaluation for coronary artery bypass graft surgery (CABG) have been associated to poor outcomes in the postoperative period. OBJECTIVE: To evaluate the association of high levels of hsCRP with short-term outcomes after cardiac surgery. METHODS: Prospective cohort with 331 patients who underwent CABG surgery with cardiopulmonary bypass (CPB) at our Institution. Patients were assigned to two groups according to hsCRP levels, measured before surgery: normal (N group) with <3 mg/l hsCRP; and increased (A group) with >= 3 mg/l hsCRP. This cutoff of 3 mg/l had a sensitivity and specificity of 60% for predicting respiratory infection, with a power of 90%. The patients were followed-up during the in hospital period. RESULTS: The mean age was 60 years, and 71.6% of the patients were male. HsCRP was increased (group A) in 144 patients (43.5%). In-hospital mortality was 4.8% and the most frequent complications in both groups were: overall infections (18%), respiratory infections (16%), atrial fibrillation (15%) and acute myocardial infarction (7.6%). The incidence of postoperative overall infections was 14.4% in the N group and 23.6% in the A group (P=0.046). Respiratory infections were also more frequent in the A group (21.5% vs. 11.8%; p = 0.024). Multivariate analyses showed that hsCRP level represented an independent predictor of postoperative respiratory infection (OR=2.08, 95% IC = 1.14-3.79). CONCLUSION: High preoperative hsCRP level is an independent predictor of respiratory infections in the mid-term postoperative period of elective coronary artery bypass graft surgery. PMID- 21971636 TI - Insulin resistance and its association with metabolic syndrome components. AB - BACKGROUND: Individuals with insulin resistance are more prone to the development of metabolic syndrome (MS), Type 2 Diabetes Mellitus and Cardiovascular Disease (CVD) OBJECTIVE: To evaluate the association between insulin resistance (IR) and metabolic syndrome components. METHODS: Cross-sectional study of 196 individuals between 2 and 18 years, treated at the Brazilian Public Healthcare system. The association of IR with the MS components was evaluated by Chi-square test, adopting the Homeostasis model assessment-insulin resistance (HOMA-IR) value > 2.5, and by analysis of variance (ANOVA) and Tukey's test, by comparing the means of the components in the HOMA-IR quartiles. Statistical analysis was performed using SPSS 17.0 software and significance level was set at 5%. RESULTS: IR was observed in 41.3% of the studied population and was associated with age between 10-18 years (p = 0.002 PR = 3.2), to MS in both sexes [Male (p = 0.022 PR = 3.7) and female (p = 0.007 PR = 2.7)] and altered triglycerides (p = 0.005 PR = 2.9) in females. The mean values of the MS components differed significantly between HOMA-IR quartiles (p <0.01), except for HDL-cholesterol. CONCLUSION: Insulin resistance can be considered a marker of cardiovascular risk. PMID- 21971637 TI - Comparison of anti-scatter grids for digital imaging with use of a direct conversion flat-panel detector. AB - Our purpose in this study was to establish a selection standard for anti-scatter grids for a direct conversion flat-panel detector (FPD) system. As indices for grid evaluation, we calculated the selectivity, Bucky factor, and the signal-to noise ratio improvement factor (SIF) by measuring rates of scatter transmission, primary transmission, and total transmission (based on the digitally displayed measurement values of the FPD system), using 4 acrylic phantoms of different thicknesses. The results showed that the SIF was less than 1.0 when the phantom thickness was 5 cm. When the phantom thickness was 25 cm and the grid ratio was 16:1, the SIF was 1.505 and 1.518 (maximum value) at 90 and 120 kV, respectively. Compared with the grid ratio of 12:1, the SIF at the grid ratio 16:1 was improved by 6.1% at 90 kV, and by 7.0% at 120 kV. In a direct-conversion FPD system, the grid ratio of 16:1 is considered adequate for eliminating the scattered-radiation effect when much scattered radiation is present, such as with a thick imaged object or a high X-ray tube voltage. PMID- 21971638 TI - TWIST expression in hypopharyngeal cancer and the mechanism of TWIST-induced promotion of metastasis. AB - The transcription factor TWIST is an important factor in regulating epithelial mesenchymal transition (EMT) and tumor metastasis. To explore the functions of TWIST in hypopharyngeal cancer, we investigated if overexpression of TWIST has an effect on FaDu cell morphology, and if alteration of TWIST has an effect on E cadherin, N-cadherin, c-fos, MMP-9, as well as in cell migration, and the invasion ability of FaDu cells. Moreover, we also studied the relationship between TWIST overexpression and clinicopathological characteristics in hypopharyngeal cancer tissue samples by immunohistochemical assays. The results showed that overexpression of TWIST-induced morphological changes, such as occurrence of EMT. TWIST overexpression also increased cell migration and invasion ability, accompanied by an alteration of E-cadherin, N-cadherin, c-fos and MMP-9 expression. Furthermore, immunohistochemical assays showed that TWIST overexpression was related with tumor differentiation (P=0.038), tumor size (P=0.048) and lymph node metastasis (P=0.044). The data presented reveal that overexpression of TWIST plays a significant role in the metastasis of hypopharyngeal tumors, and alteration of TWIST has an effect on the EMT, c-fos and MMP-9 expression in FaDu cells. We conclude that TWIST promotes hypopharyngeal carcinoma metastasis, and the TWIST/c-fos/MMP-9 signaling pathway may play an important role in the metastasis of FaDu cells. PMID- 21971641 TI - Detection of KRAS mutations in colorectal cancer with Fast COLD-PCR. AB - Patients with metastatic colorectal carcinoma (mCRC) carrying activating mutations of the KRAS gene do not benefit from treatment with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies. Therefore, KRAS mutation testing of mCRC patients is mandatory in the clinical setting for the choice of the most appropriate therapy. Co-amplification-at-lower denaturation-temperature PCR (COLD-PCR) is a novel modification of the conventional PCR method that selectively amplifies minority alleles from a mixture of wild-type and mutant sequences irrespective of the mutation type or position within the sequence. In this study, we compared the sensitivity of a COLD-PCR method with conventional PCR/sequencing and the real-time PCR-based Therascreen kit to detect KRAS mutations. By using dilutions of KRAS mutant DNA in wild-type DNA from colon cancer cell lines with known KRAS status, we found that Fast COLD-PCR is more sensitive than the conventional PCR method, showing a sensitivity of 2.5% in detecting G>A and G>T mutations. The detection of G>C transversions was not improved by either Fast COLD-PCR or Full COLD-PCR. We next analyzed by COLD-PCR, conventional PCR and Therascreen 52 formalin-fixed paraffin-embedded samples from mCRC patients. Among 36 samples with >30% tumor cells, 8 samples were negative by conventional PCR, Therascreen and Fast COLD-PCR; 20 mutations identified by conventional PCR were confirmed by Therascreen and Fast COLD-PCR; 8 cases undetermined by conventional PCR were all confirmed to carry KRAS G>A or G>T mutations by using either Therascreen or Fast COLD-PCR. Conventional PCR was able to detect only 2 KRAS mutations among 16 samples with <30% tumor cells (12.5%), whereas Therascreen and Fast COLD-PCR identified 6 mutants (37.5%). These data suggest that Fast COLD-PCR has a higher clinical sensitivity as compared with conventional PCR in detecting G>C to A>T changes in the KRAS gene, which represent >90% of the mutations of this oncogene in CRC. PMID- 21971643 TI - Change in urinary 8-hydroxydeoxyguanosine in idiopathic nephrotic syndrome. PMID- 21971642 TI - Microalbuminuria in children with primary and white-coat hypertension. AB - Microalbuminuria serves as an early marker of hypertension-related renal damage in adults. However, data on the prevalence of microalbuminuria in paediatric hypertensive patients in general and in children with white-coat hypertension (WCH) specifically are lacking. The aim of our study was to investigate the prevalence of microalbuminuria in children with primary hypertension (PH) and WCH, respectively. This was a retrospective case review of children with PH and WCH treated at three paediatric nephrology centres. Untreated children with either form of hypertension for whom measurements of urinary albumin excretion (UAE) had been performed were enrolled in the study. The study cohort comprised 52 children (39 boys) with hypertension (26 children with PH, 26 with WCH). Microalbuminuria (>3.2 mg/mmol creatinine) was present in 20% of children with PH and none of the children with WCH (p < 0.01). Children with PH had a higher median UAE than those with WCH (1.27 +/- 1.92 vs. 0.66 +/- 0.46 mg/mmol creatinine, p < 0.05). Based on these results, we suggest that children with PH have an increased prevalence of microalbuminuria, while children with WCH show no signs of hypertension-related renal damage. PMID- 21971644 TI - The effect of skin entry site, needle angulation and soft tissue compression on simulated antegrade and retrograde femoral arterial punctures: an anatomical study using Cartesian co-ordinates derived from CT angiography. AB - PURPOSE: Safe femoral arterial access is an important procedural step in many interventional procedures and variations of the anatomy of the region are well known. The aim of this study was to redefine the anatomy relevant to the femoral arterial puncture and simulate the results of different puncture techniques. METHODS: A total of 100 consecutive CT angiograms were used and regions of interest were labelled giving Cartesian co-ordinates which allowed determination of arterial puncture site relative to skin puncture site, the bifurcation and inguinal ligament (ING). RESULTS: The ING was lower than defined by bony landmarks by 16.6 mm. The femoral bifurcation was above the inferior aspect of the femoral head in 51% and entirely medial to the femoral head in 1%. Simulated antegrade and retrograde punctures with dogmatic technique, using a 45-degree angle would result in a significant rate of high and low arterial punctures. Simulated 50% soft tissue compression also resulted in decreased rate of high retrograde punctures but an increased rate of low antegrade punctures. CONCLUSIONS: Use of dogmatic access techniques is predicted to result in an unacceptably high rate of dangerous high and low punctures. Puncture angle and geometry can be severely affected by patient obesity. The combination of fluoroscopy to identify entry point, ultrasound-guidance to identify the femoral bifurcation and soft tissue compression to improve puncture geometry are critical for safe femoral arterial access. PMID- 21971645 TI - The lumbosacral plexus: anatomic considerations for minimally invasive retroperitoneal transpsoas approach. AB - PURPOSE: The minimally invasive transpsoas approach can be employed to treat various spinal disorders, such as disc degeneration, deformity, and lateral disc herniation. With this technique, visualization is limited in comparison with the open procedure and the proximity of the lumbar plexus to the surgical pathway is one limitation of this technique. Precise knowledge of the regional anatomy of the lumbar plexus is required for safe passage through the psoas muscle. The primary objective of this study was to determine the anatomic position of the lumbar plexus branches and sympathetic chain in relation to the intervertebral disc and to define a safe working zone. The second objective was to compare our observations with previous anatomical studies concerning the transpsoas approach. METHODS: A total of 60 lumbar plexus in 8 fresh cadavers from the Department of Anatomy were analyzed in this study. Coronal and lateral X-Ray images were obtained before dissection in order to eliminate spine deformity or fracture. All cadavers were placed in a lateral decubitus position with a lateral bolster. Dissection of the lumbar plexus was performed. All nerve branches and sympathetic chain were identified. Intervertebral disc space from L1L2 to L4L5 was divided into four zones. Zone 1 being the anterior quarter of the disc, zone 2 being the middle anterior quarter, zone 3 the posterior middle quarter and zone 4 the posterior quarter. Crossing of each nervous branch with the disc was reported and a safe working zone was determined for L1L2 to L4L5 disc levels. A safe working zone was defined by the absence of crossing of a lumbar plexus branch. RESULTS: No anatomical variation was found during blunt dissection. As described previously, the lumbar plexus is composed of the ventral divisions of the first four lumbar nerves and from contributions of the sub costal nerve from T12. The safe working zone includes zones 2 and 3 at level L1L2, zone 3 at level L2L3, zone 3 at level L3L4, and zone 2 at level L4L5. No difference was observed between right and left sides as regards the relationships between the lumbar plexus and the intervertebral disc. CONCLUSION: We observed some differences concerning the safe working zone in comparison with other cadaveric studies. The small number of cadaveric specimens used in anatomical studies probably explains theses differences. The minimally invasive transpsoas lateral approach was initially developed to reduce the complications associated with the traditional procedure. The anatomical relationships between the lumbar plexus and the intervertebral disc make this technique particularly risky a L4L5. Alternative techniques, such as transforaminal interbody fusion (TLIF), posterior lumbar interbody fusion (PLIF) or anterior interbody fusion (ALIF) should be used at this level. PMID- 21971646 TI - Applications of stereospecifically-labeled Fatty acids in oxygenase and desaturase biochemistry. AB - Oxygenation and desaturation reactions are inherently associated with the abstraction of a hydrogen from the fatty acid substrate. Since the first published application in 1965, stereospecific placement of a labeled hydrogen isotope (deuterium or tritium) at the reacting carbons has proven a highly effective strategy for investigating the chemical mechanisms catalyzed by lipoxygenases, hemoprotein fatty acid dioxygenases including cyclooxygenases, cytochromes P450, and also the desaturases and isomerases. This review presents a synopsis of all published studies through 2010 on the synthesis and use of stereospecifically labeled fatty acids (71 references), and highlights some of the mechanistic insights gained by application of stereospecifically labeled fatty acids. PMID- 21971649 TI - Effect of short-term ornithine alpha-ketoglutarate pretreatment on intestinal ischemia-reperfusion in rats. AB - PURPOSE: To investigate the effects of preventive enteral administration of ornithine alpha-ketoglutarate (OKG) in an ischemia-reperfusion rat model. METHODS: Sixty rats were randomized into five groups (G1-G5, n = 12). Each group was divided into two subgroups (n = 6) and treated with calcium carbonate (CaCa) or OKG by gavage. Thirty minutes later, the animals were anesthetized with xylazine 15mg + ketamine 1mg ip and subjected to laparotomy. G1-G3 rats served as controls. Rats in groups G4 and G5 were subjected to ischemia for 30 minutes. Ischemia was achieved by clamping the small intestine and its mesentery, delimiting a segment of bowel 5 cm long and 5 cm apart from the ileocecal valve. In addition, G5 rats underwent reperfusion for 30 minutes. Blood samples were collected at the end of the laparotomy (G1), after 30 minutes (G2, G4) and 60 minutes (G3, G5) to determine concentrations of metabolites (pyruvate, lactate), creatine phosphokinase (CPK), thiobarbituric acid reactive substances (TBARS) and glutathione (GSH). RESULTS: There was a significant decrease in tissue pyruvate and lactate and plasma CPK levels in OKG-treated rats at the end of reperfusion period. GSH levels did not change significantly in ischemia and reperfusion groups. However, TBARS levels increased significantly (p<0.05) in tissue samples in OKG-treated rats subjected to ischemia for 30 minutes. CONCLUSION: Short-term pretreatment with OKG before induction of I/R decreases tissue damage, increases pyruvate utilization for energy production in the Krebs cycle and does not attenuate the oxidative stress in this animal model. PMID- 21971647 TI - Factors influencing the use and interpretation of animal models in the development of parenteral drug delivery systems. AB - Depending upon the drug and drug delivery platform, species-specific physiological differences can lead to errors in the interspecies extrapolation of drug performance. This manuscript provides an overview of the species-specific physiological variables that can influence the performance of parenteral dosage forms such as in situ forming delivery systems, nanoparticles, microspheres, liposomes, targeted delivery systems, lipophilic solutions, and aqueous suspensions. Also discussed are those factors that can influence the partitioning of therapeutic compounds into tumors, the central nervous system and the lymphatics. Understanding interspecies differences in the movement and absorption of molecules is important to the interpretation of data generated through the use of animal models when studying parenteral drug delivery. PMID- 21971650 TI - Preconditioning with L-alanyl-glutamine reduces hepatic ischemia-reperfusion injury in rats. AB - PURPOSE: To evaluate the effects of pre-conditioning with L-alanyl-glutamine (L Ala-Gln) in rats subjected to total hepatic ischemia. METHODS: Thirty Wistar rats, average weight 300g, were randomly assigned to 3 groups (n=10): G-1- saline, G-2--L-Ala-Gln, G-3--control (Sham). G-1 and G-3 groups were treated with saline 2.0 ml or L-Ala-Gln (0.75mg/Kg) intraperitoneally (ip) respectively, 2 hours before laparotomy. Anesthetized rats were subjected to laparotomy and total hepatic ischemia (30 minutes) induced by by clamping of portal triad. Control group underwent peritoneal puncture, two hours before the sham operation (laparotomy only). At the end of ischemia (G1 and G2), the liver was reperfused for 60 minutes. Following reperfusion blood samples were collected for evaluation of alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels. Liver (medium lobe) was removed for immunohistochemistry study with antibody for Caspase-3. RESULTS: It was found a significant decrease (p<0.05) of ALT levels (270.6 +40.8 vs 83.3 +5.5 - p <0.05), LDH (2079.0 +262.4 vs. 206.6 +16.2 - p <0.05) and Caspase-3 expression (6.72 +1.35 vs. 2.19 +1.14, p <0.05) in rats subjected to I / R, comparing the group treated with L-Ala -Gln with G-2. Also, the ALT level was significantly lower (P<0.05) in G-1 and G-2 groups than in G-3 (control group). CONCLUSION: L-Ala-Gln preconditioning in rats submitted to hepatic I/R significantly reduces ALT, LDH and Caspase-3 expression, suggesting hepatic protection. PMID- 21971651 TI - Preconditioning with L-alanyl-L-glutamine in a Mongolian gerbil model of acute cerebral ischemia/reperfusion injury. AB - PURPOSE: To investigate the effect of L-alanyl-L-glutamine (L-Ala-Gln) preconditioning in an acute cerebral ischemia/reperfusion (I/R) model in gerbils. METHODS: Thirty-six Mongolian gerbils (Meriones unguiculatus), (60-100g), were randomized in 2 groups (n=18) and preconditioned with saline 2.0 ml (Group-S) or 0.75g/Kg of L-Ala-Gln, (Group-G) administered into the femoral vein 30 minutes prior to I/R. Each group was divided into three subgroups (n=6). Anesthetized animals (urethane, 1.5g/Kg, i.p.) were submitted to bilateral occlusion of common carotid arteries during 15 minutes. Samples (brain tissue and arterial blood) were collected at the end of ischemia (T0) and after 30 (T30) and 60 minutes (T60) for glucose, lactate, myeloperoxidase (MPO), thiobarbituric acid reactive substances (TBARS), glutathione (GSH) assays and histopathological evaluation. RESULTS: Glucose and lactate levels were not different in studied groups. However glycemia increased significantly in saline groups at the end of the reperfusion period. TBARS levels were significantly different, comparing treated (Group-G) and control group after 30 minutes of reperfusion (p<0.05) in cerebral tissue. Pretreatment with L-Ala-Gln promoted a significant increase in cerebral GSH contents in Group-G at T30 (p<0.001) time-point compared with Group-S. At T30 and T60, increased levels of GSH occurred in both time-points. There were no group differences regarding MPO levels. Pyknosis, presence of red neurons and intracellular edema were significantly smaller in Group-G. CONCLUSION: Preconditioning with L-Ala-Gln in gerbils submitted to cerebral ischemia/reperfusion reduces oxidative stress and degeneration of the nucleus (pyknosis) and cell death (red neurons) in the cerebral tissue. PMID- 21971652 TI - L-alanyl-glutamine dipeptide pretreatment attenuates ischemia-reperfusion injury in rat testis. AB - PURPOSE: To investigate the effect of alanyl-glutamine dipeptide (L-Ala-Gln) pre treatment on ischemia-reperfusion (I/R) injury after unilateral testicular torsion-detorsion in a comparative controlled experiment. METHODS: Forty-eight rats (150-200 g) randomly distributed into 4 groups (n=12), and distributed in 2 subgroups (n=6) each, were treated with saline 2.0 ml (G-1, G-3) or L-Ala-Gln 20%, 0.75g/kg dissolved in saline (total volume 2.0 ml) administered in the left saphenous vein 30 minutes before ischemia. Anesthetized rats were subjected to I/R induced by torsion (720 degrees ) of the right spermatic cord lasting 1h (G 1, G-2) or 3 hours (G-3, G4). Anesthesia was again applied at the end of ischemia time (T-0) for testis detorsion and 6 hours later (T-6) for orchiectomy. All operations were performed on the right testes through transverse scrotal incisions. Right orchiectomy was carried out at the end of ischemia (T-0), and 6 hours later (T-6) to evaluate the concentrations of malondialdehyde (MDA) and reduced glutathione (GSH) in the testis. RESULTS: Pretreatment with L-Ala-Gln reduced MDA contents in rat testis at the end of ischemia lasting 3 hours. There was significant increase of GSH levels in T-6 time-point after 1 hour of ischemia. GSH levels also increased in T-0 and T-6 time-points in rats subjected to ischemia for 3 hours. CONCLUSION: L-Ala-Gln administered before torsion/detorsion of the spermatic cord decreases lipid peroxidation during ischemia and protects the testis from oxidative stress by upregulating GSH levels during reperfusion. PMID- 21971653 TI - Effect of glutamine on the mRNA level of key enzymes of malate-aspartate shuttle in the rat intestine subjected to ischemia reperfusion. AB - PURPOSE: To determine the effects of oral L-glutamine (L-Gln) and the dipeptide L alanyl-glutamine (L-Ala-Gln) upon the activity of the malate-aspartate shuttle in the rat distal small intestine following ischemia and reperfusion. METHODS: Seventy-two Wistar rats (350-400g), were randomized in 2 groups (n = 36): group S (Sham) and Group T (Treatment) and divided into 12 subgroups (n = 6): A-A6, and B1-B6. The subgroups A1-A3 were subjected to sham procedures at 30 and 60 minutes. Thirty minutes before the study, rats were treated with calcium caseinate, 0.5g/Kg (subgroups A1, A4, B1, B4), L-Gln, 0.5g / kg (subgroups A2, A5, B2 and B5) or L-Ala-Gln, 0.75g/Kg (subgroups A3, A6, B3, B6), administered by gavage. Ischemia was achieved by clamping the mesenteric vessels, delimiting a segment of bowel 5 cm long and 5 cm apart from the ileocecal valve. Samples were collected 30 and 60 minutes after start of the study for real-time PCR assay of malate dehydrogenases (MDH1-2) and aspartate-aminotransferases (GOT1-2) enzymes. RESULTS: Tissue MDH and GOT mRNA expression in intestinal samples from rats preconditioned with either L-Gln or L-Ala-Gln showed no significant differences both during ischemia and early reperfusion. CONCLUSION: Activation of the malate aspartate shuttle system appears not to be the mechanism of glutamine-mediated elevation of glucose oxidation in rat intestine during ischemia/reperfusion injury. PMID- 21971654 TI - Preconditioning with oil mixes of high ratio Omega-9: Omega-6 and a low ratio Omega-6:Omega-3 in rats subjected to brain ischemia/reperfusion. AB - PURPOSE: This study aimed to assess the effects of preconditioning with mixtures of oils containing high/low ratio of omega-6/omega-3 and omega-9/omega-6, respectively, in an experimental model of cerebral ischemia-reperfusion (I/R). METHODS: Forty-two Wistar rats were randomly distributed into two groups: control (n=24) and test (n=18). Control group was subdivided in 4 subgroups (n=6): G1: Sham-Water; G2: I/R-Water; G3: Sham-Isolipidic and G4: I/R-Isolipid. The animals received water or a isolipid mixture containing omega-3 oils (8:1 ratio) and omega-9/omega-6 (0.4:1 ratio) by gavage for seven days. Test group included 3 subgroups (n=6) G5: I/R-Mix1, G: 6 I/R-Mix2 and G7: I/R-Mix3. Test group animals received oily mixtures of omega-3 (1.4:1 ratio) and omega-6 (3.4:1 ratio), differing only in source of omega-3: G5 (alpha-linolenic acid); G6 (alpha linolenic, docosahexaenoic and eicosapentaenoic acids), and G7 (alpha-linolenic and docosahexaenoic acids). On day 7 I/R rats underwent cerebral ischemia with bilateral occlusion of common carotid arteries for 1 hour followed by reperfusion for 3 hours. G1 and G3 animals underwent sham operation. Concluded the experiment, animals were decapitated and their brains sliced for red neurons (RN) count in CA3 area of the hippocampus. Variables were compared using ANOVA-Tukey test. RESULTS: The use of different mix preparations promoted a decrease in red cell count in all three groups (G5/G6/G7), compared with G2/G4, confirming the protective effect of different oil blends, regardless of omega-3 source. CONCLUSION: Pre-conditioning with mixtures of oils containing high ratio omega 6/omega-3 and low omega-9/omega-6 relationship protects brain neurons against I/R injury in an experimental model. PMID- 21971655 TI - An optimized animal model for partial and total skin thickness burns studies. AB - PURPOSE: Development of an improved animal model for studying skin burns in rats. METHODS: Twenty-four male Wistar rats were randomly assigned to four groups (n=6): G1-Control, G2- T100 degrees C, G3-T150 degrees C and G4-T200 degrees C. Two 10 x 10 mm squares were outlined with a sterile surgical marker on each side and along the vertebral column using a prepared template positioned between the anterior and posterior limbs. G2-G4 rats were subjected to 100 degrees C, 150 degrees C and 200oC thermal burns, respectively. G1 rats served as controls. Burns were inflicted by applying a copper plate connected to an electronic temperature controlling device to the dorsal skin of anesthetized rats. Four burns were produced on each animal (total area: 4 cm2/animal) leaving about 1 cm of undamaged skin between burn areas. Analgesia was administered during 24 h after burn injury by adding 30 mg codeine phosphate hemihydrate to 500 ml tap water. RESULTS: The application of 100 degrees C and 150oC resulted in partial thickness skin burns with central reepithelialization of the burned area only at 100 degrees C. In G4 group the whole thickness of the skin was injured without central reepithelialization. However, there was marginal reepithelialization in all groups. CONCLUSION: The model studied is inexpensive and easily reproducible, enabling the achievement of controlled burns with partial or total impairment of the skin in experimental animals. PMID- 21971656 TI - Acute pulmonary injury induced by experimental muscle trauma. AB - PURPOSE: To develop an easily reproducible model of acute lung injury due to experimental muscle trauma in healthy rats. METHODS: Eighteen adult Wistar rats were randomized in 3 groups (n=6): G-1- control, G-2 - saline+trauma and G-3 - dexamethasone+trauma. Groups G-1 and G-2 were treated with saline 2,0 ml i.p; G-3 rats were treated with dexamethasone (DE) (2 mg/kg body weight i.p.). Saline and DE were applied 2h before trauma and 12h later. Trauma was induced in G-2 and G-3 anesthetized (tribromoethanol 97% 100 ml/kg i.p.) rats by sharp section of anterior thigh muscles just above the knee, preserving major vessels and nerves. Tissue samples (lung) were collected for myeloperoxidase (MPO) assay and histopathological evaluation. RESULTS: Twenty-four hours after muscle injury there was a significant increase in lung neutrophil infiltration, myeloperoxidase activity and edema, all reversed by dexamethasone in G-3. CONCLUSION: Trauma by severance of thigh muscles in healthy rats is a simple and efficient model to induce distant lung lesions. PMID- 21971657 TI - Electroacupuncture stimulation using different frequencies (10 and 100 Hz) changes the energy metabolism in induced hyperglycemic rats. AB - PURPOSE: To investigate the effect of 10 and 100 Hz peripheral electro estimulation (electroacupuncture, EAc) at Zusanli (ST-36) and Zhongwan (CV-12) acupoints on blood glucose and lactate levels and tissue (liver and kidney) concentrations of lactate in hyperglycemic induced anesthetized rats. METHODS: Thirty-six rats were randomly assigned to 3 groups (n=12): G1: basal (anesthesia: ketamine (90mg kg-1 body weight)+ xylazine (10mg/kg-1 body weight, i.p.); G2: anesthesia+EA10Hz EAc and G3: anesthesia+EA100Hz EAc). EAc stimulation was delivered for 30 min at 10 mA at selected acupoints. Blood and tissue (kidney, liver) samples were collected at the end of the EAc application (n=6, T30) and 30 minutes later (n=6, T60) for biochemical analysis. G1 samples were collected at the same timepoints. ANOVA followed by Tukey's Multiple Comparison Test was used for statistical analyses. RESULTS: Glycemia decreased significantly (p<0.001) in G2/G3 rats in all timepoints. Kidney and liver lactate concentrations decreased significantly (p>0.001) in G2/G3 rats at T-60 and at T30 timepoints in G2 compared with G1 rats. Lactacedemia decreased significantly at T30 timepoint in G2 compared with G1 rats. G1/G3 tissue lactate levels were not different. CONCLUSIONS: Electroacupuncture (10 Hz) applied to St-36 and CV-12 acupoints decreases glycemia and lactacedemia and liver and kidney lactate concentrations. We hypothesize that the decrease in lactate levels may be related to greater energy production due to enhanced lactate to pyruvate conversion. Higher frequency (100 Hz) failed to promote the same effect. PMID- 21971658 TI - Experimental model of ultrasound thermotherapy in rats inoculated with Walker-236 tumor. AB - PURPOSE: To develop a model to evaluate the effects of focal pulsed ultrasound (US) waves as a source of heat for treatment of murine subcutaneous implanted Walker tumor. METHODS: An experimental, controlled, comparative study was conducted. Twenty male Wistar rats (160-300 g) randomized in 2 equal groups (G-1: Control and G-2: Hyperthermia) were inoculated with Walker-256 carcinosarcoma tumor. After 5 days G-2 rats were submitted to 45oC hyperthermia. Heat was delivered directly to the tumor by an ultrasound (US) equipment (3 MHz frequency, 1,5W/cm3). Tumor temperature reached 45o C in 3 minutes and was maintained at this level for 5 minutes. Tumor volume was measured on days 5, 8, 11, 14 e 17 post inoculation in both groups. Unpaired t-test was used for comparison. P<0.05 was considered significant. RESULTS: Tumor volume was significantly greater in day 5 and decreased in days 11, 14 and 17 in treated rats. Rats treated with hyperthermia survived longer than control animals. On the 29th day following tumor inoculation, 40% of control rats and 77.78% of hyperthermia-treated rats remained alive. CONCLUSION: The proposed model is quite simple and may be used in less sophisticated laboratory settings for studying the effects of focal hyperthermia in the treatment of malignant implanted tumours or in survival studies. PMID- 21971660 TI - Electroacupuncture attenuates liver and kidney oxidative stress in anesthetized rats. AB - PURPOSE: Investigate the effects of a single electroacupuncture (EA) session at acupoints Zusanli (ST-36) and Zhongwan (CV-12) combined in regulating oxidative stress in liver and kidney in anesthetized rats. METHODS: Eighteen healthy rats randomly assigned to 3 groups (n=6) were anesthetized intraperitoneally with ketamine (90 mg kg-1 body weight) + xylazine (10mg/kg body weight): G-1: Control (anesthesia), G-2: anesthesia+EA10 Hz and 10 mA, 10 Hz) applied to right ST-36 and CV-12 acupoints for 30 minutes. G-3 was likewise treated, using a tenfold higher frequency (100 Hz). G6PDH activity, malondialdehyde (MDA) and glutathione (GSH) levels were assayed spectrophotometrically. RESULTS: Liver MDA and GSH concentrations increased significantly in rats submitted to EA 10Hz (p<0.01) and EA 100 Hz (p<0.001), compared with control G-1. Liver and kidney G6GPH activity decreased significantly in G-2 (p<0.01) and G-3 (p<0.001) compared with G-1 in EA100 Hz rats. A similar pattern was found in kidney G6PDH activity in EA10 Hz rats. CONCLUSION: Single 30-minute EA 10/100 Hz session enhances lipid peroxidation and simultaneously reduces oxidative stress in liver and kidney tissues in a rat model. PMID- 21971659 TI - Effects of Rut-bpy (Cis-[Ru(bpy)2(SO3)(NO)]PF 6), a novel nitric oxide donor, in L-NAME-induced hypertension in rats. AB - PURPOSE: To evaluate the effect of Rut-bpy (Cis-[Ru(bpy)2(SO3)(NO)]PF 6), a novel nitric oxide donor in Nomega-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. METHODS: Twenty-four male Wistar rats were randomly assigned to four groups (n=6), named according to the treatment applied (G1-Saline, G2-Rut bpy, G3-L-NAME and G4-L-NAME+Rut-bpy). L-NAME (30 mg/Kg) was injected intraperitoneally 30 minutes before the administration of Rut-bpy (100 mg/Kg). Mean abdominal aorta arterial blood pressure (MAP) was continuously monitored. RESULTS: Mean arterial blood pressure (MAP) in G3 rats rose progressively, reaching 147+/-16 mmHg compared with 100+/-19 mm Hg in G1 rats (p<0.05). In G4 rats, treated with L-NAME+Rut-bpy, MAP reached 149+11 mm Hg while in G2 rats, treated with Rut-bpy, MAP values were 106+/-11 mm Hg. In G1 rats these values decreased progressively reaching 87+14 mm Hg after 30 minutes. An important finding was the maintenance of the MAP throughout the experiment in G2 rats. CONCLUSION: Rut-bpy does not decrease the MAP in L-Name induced hypertensive rats. However, when it is used in anesthetized hypotensive rats a stable blood pressure is obtained. PMID- 21971661 TI - Metabolic and oxidative effects of sevoflurane and propofol in children undergoing surgery for congenital heart disease. AB - PURPOSE: To evaluate the metabolic and oxidative effects of sevoflurane and propofol in children undergoing surgery for correction of congenital heart disease. METHODS: Twenty children with acyanotic congenital heart disease, scheduled for elective cardiac surgery with cardiopulmonary bypass, age range 1 day to 14 years were randomly assigned to 2 groups: Group GP, programmed to receive total intravenous anesthesia with propofol and group GS scheduled to use balanced anesthesia with sevoflurane. Exclusion criteria were cyanotic heart disease or complex, association with other malformations, severe systemic diseases, infection or children undergoing treatment and palliative or emergency surgery. Blood samples were collected at three different time-points: T0, after radial artery cannulation, T1, 30 minutes after cardiopulmonary bypass (CPB) launch and T2, at the end of procedure. Parameters analyzed included thiobarbituric acid-reactive substance (TBARS), glutathione (GLN), lactate and pyruvate plasmatic concentrations. RESULTS: TBARS, GSH, lactate and pyruvate concentrations did not change significantly by Friedman's test. Lactate/pyruvate ratio (L/P) was >10 in both groups. There was a moderate Pearson correlation for TBARS, in T1 (r=0.50; p=0.13) e T2 (r=0.51;p=0.12). Pearson correlation was high between groups during CPB (T1) for lactate (r=0.68; p=0.02), pyruvate (r=0.75; p=0.01) and L/P ratio (r=0.83; p=0.003). CONCLUSION: Anesthetic techniques investigated in this study showed a similar pattern, with no increase in metabolic substrates and oxidative stress during surgical correction of congenital heart defects in non-cyanotic children. PMID- 21971662 TI - L-alanyl-glutamine pretreatment attenuates acute inflammatory response in children submitted to palatoplasty. AB - PURPOSE: To evaluate the effects of L-alanyl-glutamine (L-Ala-Gln) pretreatment on oxidative stress, glycemic control and inflammatory response in children submitted to palatoplasty. METHODS: Thirty male children scheduled for routine palatoplasty, age range 2-10 years, were randomly assigned to 2 groups (n=15): Group A (saline, control) and Group B (L-Ala-Gln). Group A received normal saline 100 ml, delivered intravenously by infusion pump over 3 hours preceding surgical procedure. Group B was treated with L-Ala-Gln, 20% solution (0.5g/Kg), adding saline to complete 100ml. Peripheral venous blood samples were collected at 5 different time-points: T1- at the beginning of the study, 3 h prior to the surgical procedure; T2- at the end of the infusion (before the surgical procedure), T3- at the end of the surgical procedure, T4- 6 h postoperative and T5- 12 h postoperative. Parameters analyzed included glutathione (GSH), thiobarbituric acid reactive substances (TBARS), glucose, insulin, C-reactive protein (CRP) and interleukin-6 (IL-6). RESULTS: No statistically significant differences were found between groups comparing glucose, insulin, TBARS, GSH and IL-6 levels. However, glucose levels increased (P <0.001) in T4 and T5 as compared to baseline (T1) in control group as opposed to L-Ala-Gln group. IL-6 increased in both groups during the postoperative period, indicating an increased inflammatory response. L-Ala-Gln pretreatment did not suppress the increase of IL 6, but reduced the increase of postoperative CRP levels (T5, p <0.01). CONCLUSION: Pretreatment with L-Ala-Gln in children submitted to palatoplasty attenuates the inflammatory response in early post-operative period and promoted a better glycemic control. PMID- 21971663 TI - Preoperative glutamine infusion improves glycemia in heart surgery patients. AB - PURPOSE: To evaluate the effects of pre-operative L-alanyl-glutamine (L-Ala-Gln) on blood glucose control in patients with coronary obstruction, selected for myocardial revascularization. METHODS: Twenty-two patients (63+/-8 years) were randomly assigned to receive 250 ml of L-Ala-Gln 20% plus saline 750 ml (Group L- Ala-Gln, n=11) or saline 1000 ml (Group Saline, n=11) over 3 hours before operation. Pre-operative blood samples were collected 3h before (T-1) and at the beginning of the surgical procedure (T-2). Intra-operative samples were collected immediately before the start (T-3) and the end of extra-corporeal perfusion (T- 4). Post-operative samples were collected 12h (T-12) and 24h later (T-24). RESULTS: Glycemia decreased significantly in L-Ala-Gln treated patients during the intraoperative period. The same effect did not occur in saline patients. As the rate of insulin infusion, administered routinely to patients undergoing surgery with extracorporeal circulation was constant in both groups during surgery, the reduction of blood glucose in group L-Ala-Gln does not seem to be related to exogenous insulin. CONCLUSION: Pre-operative use of L-Ala-Gln improves glycemic control in patients with coronary artery occlusion, submitted to myocardial revascularization. PMID- 21971664 TI - Oxidative stress parameters in women with breast cancer undergoing neoadjuvant chemotherapy and treated with nutraceutical doses of oral glutamine. AB - PURPOSE: To evaluate the effects of oral administration of GLN on the oxidative stress in women with breast cancer undergoing neoadjuvant FAC chemotherapy (5 fluouracil 500 mg/m2+Doxorubicin 50 mg/m2+Cyclophosphamide 500 mg/m2 body surface area). METHODS: Twenty women (mean age: 51.7 years) with breast ductal carcinomas classified as T3 or T4 were included in the study, regardless of pre or post menopause status. Sachets containing glutamine 15g ("A") or milk protein 15g ("B") were prepared by a registered pharmacist. Allocation of patients was made by software program. Patients who received sachets labeled "A" were included in G1 group. The remaining patients, treated with the preparation labeled "B", were included in group G2. Sachets contents were blended in 150 ml of drinking water, and were given daily to each patient during the entire course of neoadjuvant chemotherapy. Peripheral blood samples were collected in the first day of each of the three cycles of chemotherapy before drug infusion. Tumor and normal breast samples were collected at the end of Patey's surgical procedure. Samples were analysed for GSH and TBARS contents. RESULTS: TBARS and GSH values were not different in breast healthy and tumor tissues nor blood when comparing control (G 2) and glutamine-treated (G-1) patients. Also, no significant differences were found in TBARS and GSH levels comparing different timepoints within the same group. CONCLUSION: Oral GLN (15g/kg/day) offers no protection against systemic or local oxidative stress in women with breast Ca undergoing neoadjuvant chemotherapy (FAC). PMID- 21971665 TI - Altered expression of miR-152 and miR-148a in ovarian cancer is related to cell proliferation. AB - microRNAs (miRs) are endogenous small non-coding RNAs that are aberrantly expressed in various carcinomas. miR-152 and miR-148a have not been comprehensively investigated in ovarian cancer. Thus, the aim of this study was to identify the role of miR-152 and miR-148a in epithelial ovarian cancer. Total RNA was extracted from tissues of 78 patients with epithelial ovarian cancer, 17 normal ovarian epithelium tissues and two ovarian cancer cell lines. Using quantitative real-time PCR (qRT-PCR) followed by the 2-DeltaDeltaCT method for calculating the results, we found that the expression levels of miR-152 were significantly decreased in ovarian cancer tissues compared to normal ovarian epithelium tissues (p<0.05). However, although the expression of miR-148a was also decreased in 65% of patients, no statistically significant difference in expression was found. A strong correlation was found between the expression of miR-152 and miR-148a (p<0.001, Pearson's correlation). The relationship between miR-152 or miR-148a expression levels in ovarian cancer and clinicopathological features, response to therapy and short-term survival was analyzed and the results showed that no correlation existed. In addition, we found that both miR 152 and miR-148a were down-regulated in ovarian cancer cell lines. After miR-152 or miR-148a mimics were transfected into ovarian cancer cell lines, the MTT cell proliferation assay showed that cell proliferation was significantly inhibited. Taken together, miR-152 and miR-148a may be involved in the carcinogenesis of ovarian cancer through deregulation of cell proliferation. They may be novel biomarkers for early detection or therapeutic targets of ovarian cancer. PMID- 21971666 TI - Swiss healthcare cost containment policies and their impact on anaesthetists' density and satisfaction. AB - INTRODUCTION: To control healthcare costs, Federal and Cantonal states have introduced policies to limit expenses and the number of practising physicians. It is unclear to date whether these policies have had a real impact on anaesthetists in Switzerland. The aim of the current study was to assess the density, characteristics and satisfaction of anaesthetists in Latin Switzerland and to compare the results with data collected before the introduction of cost containment policies in 2002. METHOD: We performed a cross-sectional study between March and July 2009 and included all practicing anaesthetists in Latin Switzerland. A questionnaire consisting of 103 items analysing demographics, activity and job satisfaction was used. The results were analysed and compared to a previous survey conducted in 2002. RESULTS: Compared to 2002, there was an overall 12% increase in the number of practising anaesthetists who were older and more often females (42% versus 35% in 2002 (p = 0.06)). The number of non-Swiss anaesthetists significantly increased to 19% compared to 11% in 2002 (p <0.05). In contrast, working hours in public hospitals decreased from 59 to 53 hours/week (p <0.001). The majority of anaesthetists considered that their overall personal situation was better than in the previous 10 years and 87.7% considered that these measures had no impact on their future plans. CONCLUSIONS: Implicit rationing policies introduced in Switzerland to limit healthcare costs and the number of physicians has had no impact on anaesthetists' workforce density, working conditions and overall satisfaction in Latin Switzerland. This opens the question of the real usefulness of these policies, at least for anaesthetists. PMID- 21971667 TI - Efficacy and safety of aprepitant in the prevention of chemotherapy-induced nausea and vomiting: a pooled analysis. AB - PURPOSE: A number of studies have reported that aprepitant has been used to prevent chemotherapy-induced nausea and vomiting. In this study, we aimed to analyze the efficacy and safety of aprepitant, which can provide evidence for aprepitant administration. MATERIALS AND METHODS: Fifteen trials involving patients who received moderately or highly emetogenic chemotherapy were included in this pooled analysis. Antiemetic drugs in these studies included aprepitant, dexamethasone, and 5-HT3 receptor antagonists. RESULTS: A total of 4,798 cases were investigated in these clinical trials. Compared with placebo or the standard antiemetic therapy, the cumulative incidence of emesis was significantly reduced in the patients treated with aprepitant-based (125 mg/80 mg) therapy on the first day [relative risk (RR) = 1.13, 95% confidence interval (CI) 1.10-1.16], from 2 to 5 days (RR = 1.35, 95% CI 1.22-1.48) and in the overall 5 days (RR = 1.30, 95% CI 1.22-1.39). In terms of drug safety, there was no significant difference between aprepitant-based regimens and non-aprepitant regimens. CONCLUSION: Results from the analysis suggest that aprepitant with 5-HT3 receptor antagonists and dexamethasone is highly effective in preventing nausea and vomiting in the days after administration of moderately or highly emetogenic chemotherapy (MEC or HEC) agents. PMID- 21971668 TI - Mild hepatic iron overload in dysmetabolic hyperferritinemia: MRI may overestimate the liver iron concentration values. PMID- 21971669 TI - Case-matched comparison with standard versus reduced intensity conditioning regimen in chronic myeloid leukemia patients. AB - This retrospective case-matched study evaluated the efficacy of reduced intensity conditioning (RIC) regimen on early and late allogeneic transplant outcome in chronic myeloid leukemia (CML) patients. Twenty-eight patients conditioned with RIC regimen were matched to 56 patients who received a myeloablative conditioning (MAC) regimen. The main criteria for case matching among our CML allotransplant cohort were the Gratwohl scoring system. The median score was 2 (1-4) in each group. The pretransplant disease status was first chronic phase (CP1, n = 20), CP2 (n = 2), and advanced phase (n = 6) in RIC, and CP1 (n = 46), CP2 (n = 3), and advanced phase (n = 7) in MAC. The duration of neutropenia and thrombocytopenia was shorter in RIC than MAC. The grade and duration of mucositis were less in RIC. The need for total parenteral nutrition (21% vs. 77%, p < 0.0001) and febrile neutropenic episodes (50% vs. 95%, p < 0.0001) were observed less frequently in RIC compared with MAC-given patients. Acute or chronic graft versus host diseases (GvHD) were not affected by the intensity of conditioning regimen. The incidence of transplant-related mortality was higher in MAC (7% vs. 14%, p = 0.01). Although more relapse/progression was observed in the RIC group, the probability of 5- and 10-year leukemia-free- and overall survival were similar regardless of conditioning regimen intensity (p > 0.05). In early first CP, the pair of female donor-male recipient and the development of chronic GvHD prolonged both leukemia-free survival and overall survival in multivariate analysis. According to our single-center matched-pair analysis, the use of RIC regimens in patients with low-risk CML results with toxicities less, responses later, and relapses more frequent than the MAC regimens. PMID- 21971670 TI - Importance of retinoic acid-inducible gene I and of receptor for type I interferon for cellular resistance to infection by Newcastle disease virus. AB - Newcastle disease virus (NDV) is an avian paramyxovirus with oncolytic properties which shows promising effects in the treatment of cancer. Anti-cancer effects are due to the virus ability: i) to replicate in and kill tumor cells, leading finally to their selective elimination; and ii) to induce the stimulation of antitumor activities in immune cells. NDV does not harm normal cells and has a high safety profile. In this study, we first report a direct correlation between the degree of cell resistance to NDV infection and the cellular expression of the retinoic acid-inducible gene I (RIG-I) which is a cytosolic viral RNA receptor. RIG-I plays an important role in the recognition of and response to infection by RNA viruses. We also demonstrate that impairment of the interferon (IFN) pathway through deletion of the receptor for type I IFN (IFNR1) in primary macrophages leads to NDV replication. In tumor cells, addition of exogenous IFN-alpha4 is shown to lead to tumor growth reduction and inhibition of viral replication. Finally, increase of the RIG-I concentration of tumor cells via plasmid transfection is shown to be associated with a stronger resistance to NDV infection. These findings shed new light on the crucial role played by the cytosolic receptor RIG-I and the plasma membrane receptor IFNR1 as key molecules to protect cells against infection by NDV. PMID- 21971671 TI - [Diagnosis of bovine viral respiratory diseases]. AB - Enzootic bronchopneumonia (EBP) is an infectious, multifactorial respiratory disease of cattle. Different viruses may be involved in its pathogenesis. In this study an adapted method of endoscopic bronchoalveolar lavage (BAL) of caudal parts of the right cranial lung lobe was established and evaluated. The obtained bronchoalveolar lavage fluid (BALF) served as template for the detection of BRSV, BPIV-3 and BCoV specific nucleic acids by RT-PCR. BALF samples of 44 cattle affected with respiratory disease were compared to nasal swabs in their reliability to detect the causative agent(s). In 6/7 animals tested positive for BRSV, RNA of this virus was detected in the BALF, in 4 animals it could be found in the nasal swabs. In two of the three BPIV-3 positive animals, the BALF was the only material that tested positive. The most reliable samples for detection of 15 BCoV positive animals were the nasal swabs. BAL was easy to perform, it led to severe coughing in one case and moderate worsening of dyspnoe in three cases. In conclusion this study shows that BAL of the right cranial lung lobe is in many cases the only tool to detect BRSV and BPIV-3, major viral triggers of EBP. PMID- 21971672 TI - Seroprevalence of Leptospira spp. in clinically healthy horses in Switzerland. AB - A retrospective, cross-sectional study was conducted to determine the leptospiral seroprevalence in clinically healthy horses in Switzerland. A representative sample of 615 horse sera was examined by microscopic agglutination test for the presence of antibodies against 15 Leptospira spp. serovars. In total, 58.5 % (n = 360) of the horses were positive for one or more of the antigens analysed, with 20.3 % of them showing titres >= 400. The most prevalent serovar was Pyrogenes (22.6 %), followed by serovars Canicola (22.1 %) and Australis (19.2 %). Older horses, mares, ponies and animals spending increased time on pasture exhibited significantly higher prevalence rates (p < 0.05). Moreover, the prevalence was higher in summer and autumn (p = 0.003). The high seroprevalence in healthy horses indicates that they are often exposed to or infected with Leptospira spp. without developing signs of disease. Therefore, other laboratory and clinical data should always be taken into consideration when interpreting serological test results for Leptospira spp. PMID- 21971673 TI - A case of congenital unilateral hip dysplasia in a newborn calf. AB - We describe the case of a Simmental calf with congenital unilateral hip dysplasia. In the initial physical exam, the calf was able to stand unsteady when helped and showed severe swinging lameness in the left hind limb. Unilateral hip laxity and a positive Ortolani sign indicated subluxation of the femur within the hip joint. This finding was further confirmed by radiographic examination which also showed malformation of the left femoral head and acetabulum. After a short period of clinical improvement the calf's health deteriorated and it was euthanized due to signs of severe coxarthrosis. Pathological examination of the affected hip joint revealed a severe acetabular and femoral dysplasia with an incomplete formation of the epiphysis of the femoral head and a chronic granulating coxarthritis without evidence of primary infectious events. PMID- 21971674 TI - [Necrotizing granulomatous pneumonia caused by fungal infection in a goat]. AB - This case report describes the clinical and postmortem findings in a 2.5-year-old goat with necrotizing granulomatous pneumonia. The goat was referred to our clinic because of swelling of the head and neck, which was unresponsive to treatment, dysphagia, and deterioration in general condition. Thoracic radiographs showed two soft tissue densities, about 10 cm in diameter, in the left caudodorsal lung. The goat was euthanized and a necropsy was carried out. The two lesions in the left caudodorsal lung were round, firm and clearly demarcated from the surrounding lung tissue. They contained purulent material and compromised about 70 % of the diaphragmatic lung lobe. Histological examination of the lesions revealed a dense network of hyphae characteristic of Mucorales spp. PMID- 21971675 TI - [Intrathoracic esophageal perforation of unknown cause in four horses]. AB - Three horses (age 17 - 23 years) were referred to the equine clinic of the University of Berne due to colic, fever, tachycardia and tachypnea. All horses showed pleural effusion. Clinical findings in 2 of the horses were highly suggestive of an intra-thoracic esophageal perforation. Severe septic pleuropneumonia without suspicion of an esophageal lesion was diagnosed in the 3rd horse. In addition, an 11 year old stallion was referred to the equine clinic for treatment of a presumptive large colon impaction. The horse was given laxatives after nasogastric intubation. Subsequent dramatic clinical deterioration and signs consistent with severe pleuropneumonia suggest that esophageal perforation had occurred when passing the nasogastric tube. All 4 horses were euthanized due to a poor prognosis. Esophageal perforation was diagnosed or confirmed post mortem in all cases. A hypertrophy of the tunica muscularis of the intra-thoracic esophagus was found in 3 of 4 horses. PMID- 21971676 TI - [In Process Citation]. PMID- 21971677 TI - [In Process Citation]. PMID- 21971678 TI - [In Process Citation]. PMID- 21971679 TI - [In Process Citation]. PMID- 21971680 TI - Associations between depressive and anxious symptoms and prenatal alcohol use. AB - Symptoms of depression and anxiety are prevalent during pregnancy and may influence women's health behaviors. The impact of women's mental health on alcohol use may be particularly important to consider as prenatal alcohol use is common and may have serious negative consequences for the developing fetus. The objectives of this study were to investigate the relationships between elevated symptoms of depression and anxiety and subsequent likelihood of any alcohol use and binge drinking during pregnancy. The sample consisted of 12,824 women from a prospective, population-based study from the United Kingdom, the Avon Longitudinal Study of Parents and Children. Participants completed questionnaires assessing alcohol use and depressive and anxious symptoms during the first and third trimesters of pregnancy. A series of multivariable regression models was fit using multiply imputed data. Thirty four percent of women reported having at least one alcoholic drink at 32 weeks' gestation and 17% reported binge drinking. We found a weak association between elevated symptoms of anxiety and any alcohol use but not between elevated symptoms of depression and any alcohol use. Modest associations were found between both elevated symptoms of depression and anxiety at 18 weeks' gestation and binge drinking at 32 weeks' gestation. Elevated symptoms of depression and anxiety may increase risk for binge drinking during pregnancy. Further research into the impact of symptoms of depression and anxiety on binge drinking during pregnancy is needed as this could represent an opportunity for public health intervention. PMID- 21971681 TI - Incremental cost burden to US healthcare payers of atrial fibrillation/atrial flutter patients with additional risk factors. AB - INTRODUCTION: Atrial fibrillation (AF) and atrial flutter (AFL) patients often have cardiovascular (CV) comorbidities, and have an increased risk of hospitalization and death. Little is known about the real-world cost burden of AF/AFL patients with additional risk factors (ARF). We evaluated the medical resource use and cost burden of AF/AFL patients with >=1 ARF (other than heart failure [HF]), in comparison with non-AF/AFL controls. METHODS: This retrospective cohort study included patients from the MarketScan Medicare database who had >=1 inpatient or >=2 outpatient AF/AFL claims. Patients were (1) >=75 years of age or (2) 70-74 years of age with >=1 ARF (hypertension, diabetes, systemic embolism, or stroke/transient ischemic attack), but without HF. The AF/AFL patients were matched on age, gender, region, and enrollment status with non-AF/AFL patients. Hospital resource use and costs over the 12-month post-index period were compared across cohorts. The impacts of comorbidity were seen by subcategorizing hospitalization as all-cause, CV-related, and AF/AFL-related. RESULTS: AF/AFL patients with >=1 ARF had a higher prevalence of comorbidity than non-AF/AFL patients (n=58,555/cohort). Hospitalizations (all-causality) were more than three times more frequent and of longer duration in AF/AFL patients with >=1 ARF than in non-AF/AFL controls (mean [SD]: 0.72 [0.87] vs. 0.21 [0.51] hospitalizations per patient per year and 3.85 [9.30] and 1.03 [4.53] days, respectively; both P<0.0001). Overall mean (SD) costs over the 12-month post index period were higher in AF/AFL patients with >=1 ARF versus the non-AF/AFL control patients for inpatient ($9613 [25,407] vs. $2625 [11,597]; P<0.0001; incremental cost $6988), outpatient ($9447 [15,062] vs. $4906 [11,715]; P<0.0001; incremental cost $4541), and prescription drug costs ($3430 [3637] vs. $2618 [3374]; P<0.0001; incremental cost $812). CONCLUSION: AF/AFL patients with >=1 ARF had significantly greater levels of comorbidity, hospitalizations, prescription, and outpatient claims than non-AF/AFL patients. The incremental costs of AF/AFL patients with >=1 ARF are largely due to higher CV-related inpatient costs. PMID- 21971684 TI - Quantitative promoter hypermethylation analysis of RASSF1A in lung cancer: comparison with methylation-specific PCR technique and clinical significance. AB - Lung cancer is the major health problem and leading cause of cancer-related deaths worldwide owing to late diagnosis and poor prognosis. Aberrant promoter methylation is an important mechanism for silencing tumor-suppressor genes in cancer and a promising tool for the development of molecular biomarkers. Ras association domain family 1A (RASSF1A), a pivotal gatekeeper of cell cycle progression, is highly methylated in a wide range of human sporadic tumors, including lung cancer. However, no significant prognostic implications have been observed in most studies qualitatively analyzed by methylation-specific PCR (MSP). We found that the RASSF1A promoter was aberrantly methylated in 44.7 and 37.4% of the tumors by pyrosequencing (PS) and MSP methods, respectively. RASSF1A methylation evaluated by the two methods was more frequent in ever-smokers and tumors with TP53 mutation than in never-smokers and tumors without TP53 mutation, respectively. Univariate and multivariate analyses revealed that strong methylation was an unfavorable prognostic factor with stage I (adjusted HR, 2.25; 95% CI 1.03-4.90; P=0.003) and squamous cell carcinoma patients (adjusted HR=2.25, 95% CI 1.03-4.90, P=0.042). Taken together, these results suggested that quantitative PS could gain wider applications in clinical samples as a promising method for early detection screening and prognosis compared with MSP. PMID- 21971686 TI - Insufficient endogenous redox buffer capacity may underlie neuronal vulnerability to cerebral ischemia and reperfusion. AB - Reactive oxygen species (ROS) are key players in ischemia-induced neurodegeneration. We investigated whether hippocampal neurons may lack sufficient redox-buffering capacity to protect against ROS attacks. Using organotypic hippocampal slice cultures (OHSCs) transiently exposed to oxygen and glucose deprivation (OGD) and gerbils suffering from a two-vessel occlusion (2VO) as complementary ex vivo and in vivo models, we have elucidated whether the intrinsic redox systems interfere with ischemia-induced neurodegeneration. Cell- type-specific immunohistological staining of hippocampal slice cultures revealed that pyramidal neurons, in contrast to astrocytes and microglia, express free thiols only weakly. In addition, free thiol levels were extensively decreased throughout the hippocampal formation immediately after OGD, but recovered within 24 hr after reperfusion. In parallel, progressive glia activation and proliferation were observed. Increased neuronal exposure to ROS was monitored by dihydroethidium oxidation in hippocampal pyramidal cell layers immediately after OGD. Coadministration of reduction equivalents (alpha-lipoic acid) and thiol stimulating agents (enalapril, ambroxol) decreased ischemia-induced neuronal damage in OGD-treated OHSCs and in gerbils exposed to 2VO, whereas single drug applications remained ineffective. In summary, limited redox buffering capacities of pyramidal neurons may underlie their exceptional vulnerability to cerebral ischemia. Consistently, multidrug treatments supporting endogenous redox systems may offer a strategy to promote valid neuroprotection. PMID- 21971687 TI - Testosterone therapy delays cardiomyocyte aging via an androgen receptor independent pathway. AB - The testicular feminized (Tfm) mouse carries a nonfunctional androgen receptor (AR) and reduced circulating testosterone levels. We used Tfm and castrated mice to determine whether testosterone modulates markers of aging in cardiomyocytes via its classic AR-dependent pathway or conversion to estradiol. Male littermates and Tfm mice were divided into 6 experimental groups. Castrated littermates (group 1) and sham-operated Tfm mice (group 2, N = 8 each) received testosterone. Sham-operated Tfm mice received testosterone in combination with the aromatase inhibitor anastrazole (group 3, N = 7). Castrated littermates (group 4) and sham operated untreated Tfm mice (group 5) were used as controls (N = 8 and 7, respectively). An additional control group (group 6) consisted of age-matched non castrated littermates (N = 8). Cardiomyocytes were isolated from the left ventricle, telomere length was measured by quantitative PCR and expression of p16INK4alpha, retinoblastoma (Rb) and p53 proteins was detected by Western blot 3 months after treatment. Compared with group 6, telomere length was short (P < 0.01) and expression of p16INK4alpha, Rb and p53 proteins was significantly (P < 0.05) up-regulated in groups 4 and 5. These changes were improved to nearly normal levels in groups 1 and 2 (telomere length = 0.78 +/- 0.05 and 0.80 +/- 0.08; p16INK4alpha = 0.13 +/- 0.03 and 0.15 +/- 0.04; Rb = 0.45 +/- 0.05 and 0.39 +/- 0.06; p53 = 0.16 +/- 0.04 and 0.13 +/- 0.03), but did not differ between these two groups. These improvements were partly inhibited in group 3 compared with group 2 (telomere length = 0.65 +/- 0.08 vs 0.80 +/- 0.08, P = 0.021; p16INK4alpha = 0.28 +/- 0.05 vs 0.15 +/- 0.04, P = 0.047; Rb = 0.60 +/- 0.06 vs 0.39 +/- 0.06, P < 0.01; p53 = 0.34 +/- 0.06 vs 0.13 +/- 0.03, P = 0.004). In conclusion, testosterone deficiency contributes to cardiomyocyte aging. Physiological testosterone can delay cardiomyocyte aging via an AR-independent pathway and in part by conversion to estradiol. PMID- 21971688 TI - An MD-PhD program in Brazil: students' concepts of science and of common sense. AB - In 1995, a pioneering MD-PhD program was initiated in Brazil for the training of medical scientists in experimental sciences at the Federal University of Rio de Janeiro. The program's aim was achieved with respect to publication of theses in the form of papers with international visibility and also in terms of fostering the scientific careers of the graduates. The expansion of this type of program is one of the strategies for improving the preparation of biomedical researchers in Brazil. A noteworthy absence of interest in carrying out clinical research limits the ability of young Brazilian physicians to solve biomedical problems. To understand the students' views of science, we used qualitative and quantitative triangulation methods, as well as participant observation to evaluate the students' concepts of science and common sense. Subjective aspects were clearly less evident in their concepts of science. There was a strong concern about "methodology", "truth" and "usefulness". "Intuition", "creativity" and "curiosity" were the least mentioned thematic categories. Students recognized the value of intuition when it appeared as an explicit option but they did not refer to it spontaneously. Common sense was associated with "consensus", "opinion" and ideas that "require scientific validation". Such observations indicate that MD PhD students share with their senior academic colleagues the same reluctance to consider common sense as a valid adjunct for the solution of scientific problems. Overcoming this difficulty may be an important step toward stimulating the interest of physicians in pursuing experimental research. PMID- 21971685 TI - Protease-activated receptor 2 signaling in inflammation. AB - Protease-activated receptors (PARs) are G protein-coupled receptors that are activated by proteolytical cleavage of the amino-terminus and thereby act as sensors for extracellular proteases. While coagulation proteases activate PARs to regulate hemostasis, thrombosis, and cardiovascular function, PAR2 is also activated in extravascular locations by a broad array of serine proteases, including trypsin, tissue kallikreins, coagulation factors VIIa and Xa, mast cell tryptase, and transmembrane serine proteases. Administration of PAR2-specific agonistic and antagonistic peptides, as well as studies in PAR2 knockout mice, identified critical functions of PAR2 in development, inflammation, immunity, and angiogenesis. Here, we review these roles of PAR2 with an emphasis on the role of coagulation and other extracellular protease pathways that cleave PAR2 in epithelial, immune, and neuronal cells to regulate physiological and pathophysiological processes. PMID- 21971690 TI - Segmentectomy of the liver. AB - Segmentectomy is anatomical resection of segments based on the classification of Couinaud. This procedure is performed mainly for hepatocellular carcinoma. Invasion of portal vein and intrahepatic metastases often occur with hepatocellular carcinoma. Thus, it is desirable to perform anatomical resection of the cancer-bearing areas for curative purpose. However, segmentectomy is selected when extensive resection must be avoided to preserve liver function. There are major differences between segmentectomy of the left hemiliver (Sg 2-4) and right hemiliver (Sg 5-8). In the former, the branches (third-order branches) arising from the umbilical portion of the portal vein can be ligated prior to liver resection. In the latter, manipulation is difficult. Therefore, ultrasonically guided segmental staining is performed by puncturing the portal branch and injecting a dye. This report described techniques for segmentectomy. PMID- 21971689 TI - Involvement of beta3-adrenergic receptors in the control of food intake in rats. AB - This study examined the food intake changes evoked by intracerebroventricular (icv) injection of a selective agonist (BRL37344, 2 and 20 nmol) or antagonist (SR59230A, 10 and 50 nmol) of beta3-adrenergic receptors in 24-h fasted rats (adult male Wistar rats, 200-350 g, N = 6/treatment). The animals were also pretreated with saline icv (SAL) or SR59230A (50 nmol) followed by BRL37344 (20 nmol) or SAL in order to determine the selectivity of the effects evoked by BRL37344 on food intake or the selectivity of the effects evoked by SR59230A on risk assessment (RA) behavior. The highest dose of BRL37344 (N = 7) decreased food intake 1 h after the treatment (6.4 +/- 0.5 g in SAL-treated vs 4.2 +/- 0.8 g in drug-treated rats). While both doses of SR59230A failed to affect food intake (5.1 +/- 1.1 g for 10 nmol and 6.0 +/- 1.8 g for 50 nmol), this treatment reduced the RA frequency (number/30 min) (4 +/- 2 for SAL-treated vs 1 +/- 1 for 10 nmol and 0.5 +/- 1 for 50 nmol SR59230A-treated rats), an ethological parameter related to anxiety. While pretreatment with SR59230A (7.0 +/- 0.5 g) abolished the hypophagia induced by BRL37344 (3.6 +/- 0.9 g), BRL37344 suppressed the reduction in RA frequency caused by SR59230A. These results show that the hypophagia caused by BRL37344 is selectively mediated by beta3-adrenergic receptors within the central nervous system. Moreover, they suggest the involvement of these receptors in the control of anxiety. PMID- 21971691 TI - Control of the inflow and outflow system during liver resection. AB - Control of blood loss is a serious problem during liver resection. Bleeding from the inflow system can be controlled by the Pringle maneuver. The time limit for clamping is up to 10-15 min. A shortcoming of the Pringle maneuver is that it causes blood congestion in the portal vein. To avoid this problem other techniques have been developed including selective vascular occlusion and selective clamping of segmental branches. Bleeding from the outflow system is closely related to central venous pressure (CVP). Lowering the CVP reduces blood loss; in particular, keeping CVP <5 cmH(2)O by anesthesiological management is a simple and effective way to reduce blood loss. CVP remains high in some cases despite anesthesiological efforts, but in these circumstances other techniques are available including inferior vena cava clamping below the liver and intraoperative blood salvage. PMID- 21971693 TI - [Psychooncological interventions - what do cancer patients aged 60 years or older wish for?]. AB - OBJECTIVES: To determine the acceptance of psychooncological interventions and predictors of subjective needs in cancer patients over 60 years of age. METHODS: We examined 292 in- and outpatients (51% female, 51.7% aged over 60 years) from the Interdisciplinary Cancer Center of the University Hospital of Munster with a questionnaire designed to assess their wish to participate in various psychooncological interventions (FIPA) and with the Hospital Anxiety and Depression Scale (HADS-D). RESULTS: 73.5 % of those over 60 years and 87.9 % of those under 60 years professed a wish for at least one specific psychooncological intervention. Higher age, lower levels of anxiety and cancer relapse were negative predictors of the readiness to attend psychooncological interventions (9 % variance explained). As to specific interventions, those aged 60 years or older showed lower acceptance only for relaxation techniques. CONCLUSIONS: Readiness to attend psychooncological interventions was high with only marginal differences between the age groups. Because objective features of the patient and the disease resulted only in a low predictability of the subjective need for psychooncological interventions, routine screening of cancer patients seems an important issue. PMID- 21971692 TI - Ethanol extract of Prunella vulgaris var. lilacina inhibits HMGB1 release by induction of heme oxygenase-1 in LPS-activated RAW 264.7 cells and CLP-induced septic mice. AB - The ethanol extract of the flower of P. vulgaris var. lilacina (EEPV) has been used traditionally as an antiinflammatory agent in many countries. Inducers of heme oxygenase-1 (HO-1) reduce high mobility group box 1 (HMGB1), a late phase cytokine, in sepsis. Although EEPV has been used as an antiinflammatory agent, no report is available as to whether it modifies HMGB1 in sepsis due to HO-1 induction. It was found that EEPV increased HO-1 protein expression in RAW 264.7 cells, which was significantly inhibited by LY294002, but not PD98059, SB203580 or SP600125. In addition, EEPV activated NF-E2-related factor (Nrf2) to move from the cytosol to the nucleus, and EEPV-induced HO-1 and activation of ARE luciferase activity were significantly reduced by siNrf2 transfection and LY294002 but not SB203508. EEPV also significantly inhibited NF-kappaB luciferase activity, and decreased both iNOS/NO and COX-2/PGE(2) production in lipopolysaccharide (LPS)-stimulated macrophages which was reversed by siHO-1 RNA transfection. Importantly, EEPV inhibited HMGB1 release in LPS-activated macrophages in a PI3K-sensitive manner and reduced serum HMGB1 level and lung HMGB1 expression in cecal ligation and puncture (CLP)-induced septic mice. It is concluded that EEPV induces HO-1 expression through PI3K/Nrf2 signal pathways, which may be beneficial for the treatment of sepsis due to a reduction of HMGB1 release. PMID- 21971694 TI - [Outcome and catamnesis of psychosomatic hospital treatment of 60+-year-old inpatients]. AB - OBJECTIVES: The catamnesis study examined the effectiveness of inpatient psychotherapy of patients 60+ years of age 1 to 2 years after the treatment. The patients had been treated in the years 2007 and 2008. METHOD: Systematic pre and post inpatient treatment data were available for all patients, collected according to Psy-BaDo. For the purpose of the catamnesis the patients received the complaint questionnaire SCL-90-R as self-evaluation questionnaire, based on a shortened form of the BSI. In addition, we also used a special catamnesis questionnaire developed by the inpatient Group Therapy Research Unit staff and revised at the Rhein-Klinik (Wuchner u. Hess 2005). RESULTS: According to their self-assessments, most patients reported of having gained a "good" to "very good" benefit from the treatment. The effectiveness of the inpatient treatment was high both at the end of the treatment and at the time of the catamnesis (discharge d = 0.86; catamnesis d = 0.84).Nearly 70 % of the patients were also later treated by outpatient psychotherapy, 51 % were prescribed psychopharmacologic drugs and 33 % other forms of medicine. DISCUSSION: The therapeutic framework for the treatment of older patients corresponded to the rules for psychosomatic medicine and psychotherapy. There is no need for any other fundamentally different concepts. After the follow-up outpatient treatments, older patients and the therapists expressed an increased acceptance of psychotherapy. The effectiveness of treatment in older patients may result from their good resources. The results of the catamnesis show encouraging findings for the psychosomatic treatment of older patients, also in the long term from 1,5 to 2 years. PMID- 21971695 TI - [The so-called body-mind problem]. AB - THE PROBLEM: Even psychosomatic researchers seem to want to avoid the so-called body-mind problem, which is actually a mind-brain problem. In line with Beckermann (2008), the first the four possible positions on the mind-brain problem are presented. The debate over the past 100 years has revolved around the question of whether mental events are ontologically independent of brain physiology or whether they are in fact entirely determined by it. Such a physicalism approach based on properties (i.e., mental characteristics or phenomena are physical or can be completely reduced to physical characteristics), however, is diametrically opposed to some of our strongest intuitions, e.g., that computers will never be able to develop qualities of human experience (qualia) and thus become subjects in the first person singular. Yet we are equally unable to prove the fundamental impossibility of such a development. THESIS: In this stalemate situation, a differentiation was undertaken by Gottlob Frege (1892) which could be of help: Expressed in today's language, a distinction is made between the sense of an expression, its contextual presentation (e.g., where there is a difference between "the evening star" and "the morning star"), on the one hand, and its so-called reference (the object to which it refers, here the planet Venus in both cases) on the other. The school of Gestalt psychology that developed in Berlin at the start of the last century similarly posited a "psychophysical level of the CNS," a continuum in a pattern of electrical field forces which manifests itself first in cerebral physiological-neuronal processes as well as in other perspectives such as consciousness and experience. A subsequent speculative concept then extends this model to assume also an (as yet) unknown Alpha configuration as being a common reference of two sense contents: (1) the results of the neurophysiological third-person perspective and (2) of the emotional-cognitive first-person perspectives. Only through the latter will Alpha be able to become self-conscious and an instance acting in his world. RESULTS: Only through the latter will Alpha be able to become self-conscious and an instance acting in his world. The postulate of an Alpha configuration thus retains the possibility of a biology not (yet) accessible to our knowledge, such that our fundamental conviction regarding the holism of soma and psyche can be maintained for us as medical practitioners and scientific physicians. Our patients need both, our medical-scientific competence (3rd-person perspective) as well as our empathic sensibility in exploring their phenomenal experience (1st person perspective). They need us as medical artists. PMID- 21971696 TI - [Assessment and treatment of patients with nonepileptic dissociative seizures in a department of epileptology]. AB - OBJECTIVES: We examined the frequency of dissociative seizures in inpatients of a specialized ward for epilepsy as well as their diagnostic and therapeutic course. The basic principle of the latter is the therapeutic triad of value-free communication of the diagnosis, training of techniques for seizure interruption and problem solving of inner conflicts. METHODS: All inpatients in a department of epileptology with a diagnosis of dissociative seizures were examined retrospectively for the year 2009. RESULTS: 65 patients (11 %) were diagnosed with dissociative seizures, 23 patients with a primary diagnosis of epilepsy and 42 with a secondary diagnosis, epilepsy being the primary diagnosis. Symptoms occurred in the 23 patients with dissociative seizures as primary diagnosis between 2 weeks and 40 years. Possible predisposing factors and psychological comorbidities for the development of dissociative seizures were manifold. A psychopharmacological medication was established in 9 patients (39 %), and psychotherapy was recommended explicitly in all patients. CONCLUSIONS: There is a great heterogeneity in patients with dissociative seizures with a sometimes long course of the disorder. PMID- 21971697 TI - Executive functions in Parkinson's disease: systematic review and meta-analysis. AB - Impairment of executive function (EF) is commonly reported as a feature of PD. However, the exact pattern of executive impairment remains unclear. Also, there is an ongoing discussion surrounding the definition and conceptualization of EF, which might affect the clarity of research evidence on cognition in PD. The aim of this systematic review was to describe the pattern of executive impairment in early-stage PD emerging from the research literature and to identify critical issues for improving consistency in this field. The PsychInfo, MEDLINE, Science Direct, CINAHL, and Cochrane Library databases were searched using the term "Parkinson's disease" combined with each of 14 cognitive abilities defined as representing aspects of EF. The review was limited to studies that investigated EF as the central variable in early-stage, nondemented PD patients. The review identified 33 studies of EF that were operationalized in terms of 30 abilities tested by 60 measures and variously interpreted. Many measures were used only once, so only a small part of the available research evidence could be synthesized in the meta-analysis. The meta-analysis was undertaken using data from five commonly used tests of EF drawn from 18 studies. This revealed consistent evidence for cognitive difficulties across all five EF tests. Research on EF in PD is characterized by a considerable lack of clarity with regard to measure selection and interpretation. The findings support the view that EF impairments are evident in PD. However, the clinical significance of the cognitive abnormalities reported has yet to be clarified. PMID- 21971698 TI - Psychotropic medication use in Swiss nursing homes. AB - BACKGROUND: Psychotropic medication is commonly used in nursing homes, to treat behavioural and psychological symptoms of dementia (BPSD) for example. Treatment with antipsychotics may improve BPSD in some residents but can be associated with serious side effects, such as higher mortality, faster disease progression and cerebrovascular events. In the current study, psychotropic medication use was analysed in a representative sample of nursing home residents in the German speaking part of Switzerland, at entry and during follow-up. METHODS: Retrospective analysis of the Resident Assessment Instrument Minimum Data Set (RAI-MDS) of 90 nursing homes at entry (n = 18853) and during follow-up (n = 12101). RESULTS: At entry, 7580 residents (40.2%) were diagnosed with dementia and 49.0% of them had behavioural symptoms. Residents with dementia received more psychotropic medication than residents without dementia (70.8% vs. 55.0%; p<0.001). The most commonly prescribed medications were antipsychotics (demented 44.8% vs. non-demented 17.4%; p<0.001) and antidepressants (demented 29.6% vs. non-demented 26.7%; p<0.001). Antipsychotics were mainly prescribed for residents with dementia and behavioural disturbances. The longitudinal analysis revealed that most residents with dementia (69.5%) took antipsychotics continuously from entry to the final assessment and the same was true for antidepressants (66.1%). The use of antipsychotics at baseline in residents with dementia predicted (p<0.001) the use of antipsychotics during follow-up. CONCLUSIONS: The long term use of antipsychotics in nursing homes may need to be reconsidered in view of novel treatment recommendations, suggesting that the prescription of antipsychotics for patients with dementia should be a second line treatment, restricted to symptoms of psychosis or severe aggression, and prescribed for the shortest duration possible. PMID- 21971699 TI - Spontaneous intracranial hypotension: case reports and literature review. AB - The clinical syndrome of spontaneous intracranial hypotension (SIH) was first proposed in 1938 and describes a headache syndrome virtually identical to the headaches, which may follow dural puncture. Orthostatic headache, low cerebrospinal fluid opening pressure, and diffuse meningeal enhancement on post contrast T1-weighted MRI brain studies are the major features of this increasingly recognised syndrome. We describe a case series of patients diagnosed with SIH, their treatment and outcome, and a review of the literature. We propose that this is an important cause of new daily persistent headaches, which is usually relatively easy to diagnose, and if recognised early, is eminently treatable. PMID- 21971700 TI - Correlations among ERCC1, XPB, UBE2I, EGF, TAL2 and ILF3 revealed by gene signatures of histological subtypes of patients with epithelial ovarian cancer. AB - The aim of this study was to better understand the mechanisms of tumor development and disease progression in human epithelial ovarian cancer. Fifty genes were screened for gene signature; 20 expressed genes were assessed in tumor and normal samples of EOC patients by RT-PCR. Expression of UBE2I, EGF, TAL2 and ILF3 was validated by qPCR on the ABI Prism 7000 Detection System. ERCC1 and XPB expression was previously determined by RT-PCR in these specimens. Statistical analyses include two-sided Kruskal-Wallis test, pairwise comparison, Pearson correlation coefficient and paired t-test. In comparison to normal samples, 6 genes demonstrated distinct expression patterns in tumor tissues, with high expression observed for ERCC1, XPB and ILF3 (p=0.001, 0.0007 and 0.002, respectively) and low expression observed for TAL2 and EGF (both p<0.0001). This differential expression pattern between normal and tumor tissues may reflect in part the development of ovarian cancer. Significant differences in expression patterns of these genes in clear cell, endometrioid, mucinous and serous ovarian cancer were observed. Comparison of expression of any two EOC subtypes revealed multiple gene involvement in histopathological differentiation and cancer progression. A positive association was found between ERCC1 and XPB expression (r=0.53, p<0.0001) and between TAL2 and EGF expression (r=0.817, p<0.0001) suggesting the existence of gene linkage in these tumors. The differences in expression patterns of studied genes between tumors and normal specimens, between histological subtypes and correlations among studied genes, may indicate their involvement in tumor growth and disease progression in human epithelial ovarian cancer. Further investigation of these genes may enable better understanding of the molecular mechanism of tumorigenesis and identification of potential biomarkers. PMID- 21971701 TI - Detection of antibody against fungal glucosylceramide in immunocompromised patients: a potential new diagnostic approach for cryptococcosis. AB - We have developed an ELISA to determine the value of anti-glucosylceramide antibody for the prediction of disseminated cryptococcosis in immunocompromised subjects and performed a clinical prospective study at the Medical University of South Carolina. The study enrolled a total of 53 patients who were free of active fungal diseases at the time of enrollment but at risk of developing one because they were all immunocompromised, e.g., (1) patients positive for HIV and (2) patients post- or awaiting solid organ transplantation. Among 53 patients enrolled, two patients developed invasive cryptococcosis, and in both patients, IgM anti-GlcCer was detected in sera using the ELISA at least 6 weeks prior to the clinical presentation of the brain disease. These results were corroborated by a cryptococcal antigen lateral flow assay, which was also positive in serum prior to the development of meningoencephalitis. However, a high number of positive results were also detected in patients with no evidence of cryptococcosis. This study highlights the potential utility of this new assay in early diagnostic testing algorithms for patients at risk for cryptococcosis, but further investigations are needed to validate the sensitivity and specificity of the glucosylceramide ELISA as a predictor of cryptococcosis. PMID- 21971702 TI - Expression and characterization of Cryptococcus neoformans recombinant App1. AB - We characterized Cryptococcus neoformans recombinant antiphagocytic protein 1 (rApp1) by SDS-PAGE, gel filtration chromatography, circular dichroism, and fluorescence spectroscopy. rApp1 produced by C. neoformans var. grubii contains an odd number of cysteines; therefore, it has the ability to form intermolecular disulfide bridges which can lead to the formation of amyloid fibrils in the absence of beta-mercaptoethanol or DTT in vitro. Alternate approaches to over expression of rApp1 in the Lepidopteran High Five(TM) Insect cell line using pIZ/V5-His and in lentivirus were explored and are described. Finally, localization of App1 in vivo was examined in the presence and absence of the capsule. PMID- 21971703 TI - fac-[TcO3(tacn)]+: a versatile precursor for the labelling of pharmacophores, amino acids and carbohydrates through a new ligand-centred labelling strategy. AB - Herein, we report a protocol for the synthesis of [(99m)TcO(3)(tacn)](+) ([1](+)) (tacn = 1,4,7-triazacyclononane) that is suitable for clinical translation. Bioconjugates containing pharmacophores ([TcO(NO(2)-Imi)(tacn)](+); [3](+)), artificial amino acids ([TcO(Fmoc-allyl-His)(tacn)](+); [5](+)), and glucose derivatives ([TcO(allyl-tetraacetylglucose)(tacn)](+); [7](+)) were synthesized by cycloaddition strategies and fully characterized ((99)Tc and (99m)Tc). These new technetium complexes are stable at neutral pH and demonstrate the potential and flexibility of the [3+2] cycloaddition labelling concept. In addition to the synthetic work, the first biodistribution studies of [1](+) and the small [3+2] cycloadduct [(99m)TcO(NO(2)-Imi)(tacn)](+) ([3](+)) were completed. The biodistribution studies suggest the stability of these complexes in vivo. Furthermore, it was demonstrated that the high hydrophilicity of the [(99m)TcO(3)(tacn)](+) building block is a complement to the complexes of the fac {Tc(CO)(3)}(+) core. PMID- 21971704 TI - Clinical role of the Duke Activity Status Index in the selection of the optimal type of stress myocardial perfusion imaging study in patients with known or suspected ischemic heart disease. AB - BACKGROUND: Exercise treadmill stress myocardial perfusion imaging (MPI) with single photon emission computed tomography is commonly used to evaluate the extent and severity of inducible ischemia as well as to risk stratify patients with suspected and known coronary artery disease (CAD). Failure to reach adequate stress, defined as not attaining age-appropriate metabolic equivalents (METs), can underestimate the extent and severity of ischemic heart disease, resulting in false negative results. This study evaluates the efficacy of the Duke Activity Status Index (DASI), a simple self-administered 12-item questionnaire, as a predictor of METs achieved by treadmill stress testing. METHODS: The DASI was prospectively administered to 200 randomly selected men and women referred to the nuclear cardiology laboratory at New York University Langone Medical Center for stress MPI. Each patient was asked to complete the 12-item DASI questionnaire independently. 136 patients underwent treadmill exercise with MPI and 64 had pharmacologic stress with MPI. The association between exercise capacity in METs as estimated by the DASI questionnaire and performance on the Bruce treadmill protocol in METS was compared using chi-square statistics. RESULTS: Over 70% of those patients whose DASI score predicted the ability to perform <10 METs were unable to exercise beyond stage 2 of the Bruce protocol (7 METs). For those whose DASI score predicted ability to perform >12.5 METs, over 80% of patients reached >stage 2 of the Bruce protocol with 40% reaching beyond stage 3 (10 METs). When patient age was incorporated into the calculation, a more linear relationship was observed between predicted and obtained METs. CONCLUSION: The DASI is a simple self-administered questionnaire which is a useful pretest tool to determine a patient's ability to achieve appropriate METs. In the nuclear cardiology laboratory, the DASI has the potential to guide selection of exercise treadmill vs pharmacologic stress and ultimately improve laboratory efficiency. PMID- 21971705 TI - Identification of a hyperactive variant of the SecM motif involved in ribosomal arrest. AB - Recent studies in several organisms have shown that certain nascent sticky peptides stall in the ribosome during their own translation. Amino acid sequences present at the C-terminal part of Escherichia coli SecM ((150)FSTPVWISQAQGIRAGP(166)) have a well-characterized role in ribosome stalling. To investigate the determinants of the SecM motif responsible for ribosome stalling, we performed a genetic screen for mutants with an altered SecM motif that resulted in altered ribosome stalling. To do this, we used a cat fusion construct containing the SecM motif and a myc-tag (cat'-'myc-secM). This construct expresses cat'-'myc-secM mRNA transcripts predominantly translated by a subset of ribosomes called specialized ribosomes that recognize an altered ribosome binding sequence in the mRNA. While all of the isolated mutants containing mutations at the functionally conserved amino acid residues at positions between 161 and 166 showed decreased ribosome stalling, one mutant sequence containing an amino acid substitution from serine to lysine at position 157 (S157K) showed enhanced ribosome stalling that consequently increased mRNA cleavage. Our results reveal that a functionally not conserved amino acid residue at position 157 of SecM can also affect ribosome stalling and provide additional insight into the molecular mechanisms underlying sticky-peptide-induced ribosome arrest. PMID- 21971706 TI - Altered glutamate receptor function in the cerebellum of the Ppt1-/- mouse, a murine model of infantile neuronal ceroid lipofuscinosis. AB - The neuronal ceroid lipofuscinoses (NCLs) are a family of devastating pediatric neurodegenerative disorders and currently represent the most common form of pediatric-onset neurodegeneration. Infantile NCL (INCL), the most aggressive of these disorders, is caused by mutations in the CLN1 gene that encodes the enzyme palmitoyl protein thioesterase 1 (PPT1). Previous studies have suggested that glutamatergic neurotransmission may be disrupted in INCL, so the present study investigates glutamate receptor function in the Ppt1(-/-) mouse model of INCL by comparing the sensitivity of cultured wild-type (WT) and Ppt1(-/-) cerebellar granule cells to glutamate receptor-mediated toxicity. Ppt1(-/-) neurons were significantly less sensitive to AMPA receptor-mediated toxicity but markedly more vulnerable to NMDA receptor-mediated cell death. Because glutamate receptor function is regulated primarily by the surface expression level of the receptor, the surface level of AMPA and NMDA receptor subunits in the cerebella of WT and Ppt1(-/-) mice was also examined. Western blotting of surface cross-linked cerebellar samples showed a significantly lower surface level of the GluR4 AMPA receptor subunit in Ppt1(-/-) mice, providing a plausible explanation for the decreased vulnerability of Ppt1(-/-) cerebellar neurons to AMPA receptor-mediated cell death. The surface expression of the NR1, NR2A, and NR2B NMDA receptor subunits was similar in the cerebella of WT and Ppt1(-/-) mice, indicating that there is another mechanism behind the increased sensitivity of Ppt1(-/-) cerebellar granule cells to NMDA toxicity. Our results indicate an AMPA receptor hypofunction and NMDA receptor hyperfunction phenotype in Ppt1(-/-) neurons and provide new therapeutic targets for INCL. PMID- 21971707 TI - Synthesis and photophysical studies of phthalocyanine-gold nanoparticle conjugates. AB - This work reports on the synthesis, characterization and photophysical studies of phthalocyanine-gold nanoparticle conjugates. The phthalocyanine complexes are: tris-(5-trifluoromethyl-2-mercaptopyridine)-2-(carboxy)phthalocyanine (3), 2,9,17,23-tetrakis-[(1, 6-hexanedithiol) phthalocyaninato]zinc(II) (8) and [8,15,22-tris-(naptho)-2(amidoethanethiol) phthalocyanato] zinc(II)(10). The gold nanoparticles were characterized using transmission electron microscopy, X-ray diffraction, atomic force microscopy and UV-vis spectroscopy where the size was confirmed to be ~5 nm. The phthalocyanine Au nanoparticle conjugates showed lower fluorescence quantum yield values with similar fluorescence lifetimes compared to the free phthalocyanines. The Au nanoparticle conjugates of 3 and 10 also showed higher triplet quantum yields of 0.69 to 0.71, respectively. A lower triplet quantum yield was obtained for the conjugate compared to free phthalocyanine for complex 8. The triplet lifetimes ranged from 70 to 92 MUs for the conjugates and from 110 to 304 MUs for unbound Pc complexes. PMID- 21971708 TI - Phosphorylated T567 ezrin is associated with merlin expression in KIT-mutant gastrointestinal stromal tumors. AB - Membrane-cytoskeleton linker organizer ezrin is a member of the ERM (ezrin radixin-moesin) protein family. It has been suggested as an important element in the oncogenic process, particularly in conferring a metastatic ability on tumor cells. We hypothesized that the KIT oncogenic form is one of the proteins that modulates expression of the ezrin protein via phosphorylated ezrin at different residues; furthermore, it may interact with the protein merlin, and promoting tumor development via the PI3K or MAPK pathway. In the present study, we observed that differential expression of ezrin was a common feature in gastrointestinal stromal tumors (GISTs). We further demonstrated that cases exhibiting expression of phosphorylated Thr567 in the ezrin protein were associated with immunoactivities of KIT and merlin expression (p=0.039 and 0.013, respectively). In conclusion, GISTs harbor activation of KIT protein may induce phosphorylation of the downstream protein ezrin at certain residues, thereby triggering subsequent signal transduction cascades and driving downstream pathways of tumor progression. However, a larger series of tumor samples should be analyzed in future studies, as well as the identification of phosphorylated sites to determine the role of ezrin in tumor progression thus shedding light on clinical outcomes. PMID- 21971709 TI - Correlation between glioblastoma stem-like cells and tumor vascularization. AB - Glioblastoma multiforme (GBM) is the most lethal type of brain tumor. The formation of abnormal, dysfunctional tumor vasculature and glioblastoma stem-like cells (GSCs) are believed to be the major components of the inability to treat these tumors effectively. We analyzed 70 glioblastoma samples by immunohistochemistry and double immunofluorescence staining. The immunohistochemical expression of the putative brain tumor stem cell markers CD133 and Nestin in paraffin sections was analyzed using morphometry. In all GBM samples, CD133 or Nestin was expressed in tumor and endothelial cells. Double immunofluorescence stainings showed that the two different marked GSCs were found accumulated around the CD31+ blood vessels and CD133/CD31 or Nestin/CD31 co expression was found in the endothelial cells and GSCs. Furthermore, the vascular endothelial growth factor (VEGF) and the endothelial marker CD31 were co expressed in GSCs. Therefore, GSCs not only showed distinct perivascular distribution but were capable of differentiating into endothelial cells. We demonstrate that GSCs contribute directly to the tumor vasculature by endothelial cell differentiation. GSCs and tumor vascularization are closely related to each other, not only in the regional distribution but also in biological function. These findings describe a new mechanism for tumor vasculo-genesis and may provide new insights for targeted therapy against brain tumors. PMID- 21971710 TI - A five-year prospective study of bone mineral density in men and women with diabetes: the Fremantle Diabetes Study. AB - To examine longitudinally the effect of diabetes on bone structure and metabolism, we measured bone mineral density (BMD) and turnover markers in 26 type 1 (mean age 49 years) and 27 type 2 (mean age 65 years) diabetic patients without known osteoporosis from a community-based sample at baseline and 5 years later. In the 17 type 1 men, BMD fell at the femoral neck (0.804 +/- 0.145 vs. 0.769 +/- 0.129 g/cm(2); P = 0.003) with no change at lumbar spine or forearm. In the 11 type 2 women, BMD decreased at all sites except spine (femoral neck 0.779 +/- 0.119 vs. 0.742 +/- 0.090 g/cm(2); P = 0.019). BMD did not fall at any site in type 1 women or type 2 men. There was an increase in serum alkaline phosphatase and trend to higher serum beta carboxyl-terminal type I collagen telopeptide concentrations in the type 1 patients, and a decrease in free testosterone in the type 1 men. These data show that the rate of demineralization at the femoral neck in type 1 men is similar to that in older post-menopausal type 2 women. Changes in biochemical markers suggest that, in type 1 men, there is ineffective bone formation associated with accelerated bone resorption and lower sex steroid bioavailability. These findings may have implications for the clinical management of young male adults with diabetes. PMID- 21971711 TI - Portuguese version of the bath indexes for ankylosing spondylitis patients: a cross-cultural adaptation and validation. AB - The Bath Ankylosing Spondylitis Activity Index (BASDAI), Functional Index (BASFI), Metrology Index (BASMI), and Global Score (BASG) are commonly used to assess patients with ankylosing spondylitis (AS). The aim of this study was to cross-culturally adapt and validate these indexes into the Portuguese language. Seventy-eight patients were included in the study. After forward and backward translations, the questionnaires were administered and tested for internal consistency, test-retest reliability, face validity, content validity, and construct validity. The outcome measures HAQ, EQ-5D, and SF-36 were also implemented. Metrological parameters (BASMI components) and chest expansion were evaluated. Correlation coefficients for test-retest were 0.875, 0.937, 0.831, and 0.961 for BASDAI, BASFI, BASMI, and BASG, respectively. Internal consistency coefficients were between 0.747 and 0.953. The adapted and translated questionnaires demonstrated an acceptable comprehensibility by a panel of patients, and face validity was assured by the cognitive debriefing performed. Content validity was assured by comparing the scores obtained by the questionnaires when age and gender, age of symptoms onset, and disease duration were considered. Construct validity was assured by significant correlations established between the Bath scores and generic health status HAQ, EQ-5D and SF 36, morning stiffness duration, chest expansion, and physician disease activity assessment. The Portuguese version of the BASDAI, BASFI, BASG, and BASMI showed adequate reliability and validity in patients with AS. The measurement properties were comparable to versions in other languages, indicating that the indexes can be used for evaluation of Portuguese-speaking AS patients. PMID- 21971712 TI - Targeting IL-6 promoter polymorphism -174G/C should be dependent on ethnicity. PMID- 21971713 TI - Multidimensional profiling of plasma lipoproteins by size exclusion chromatography followed by reverse-phase protein arrays. AB - The composition of lipoproteins and the association of proteins with various particles are of much interest in the context of cardiovascular disease. Here, we describe a technique for the multidimensional analysis of lipoproteins and their associated apolipoproteins. Plasma is separated by size exclusion chromatography (SEC), and fractions are analyzed by reverse-phase arrays. SEC fractions are spotted on nitrocellulose slides and incubated with different antibodies against individual apolipoproteins or antibodies against various apolipoproteins. In this way, tens of analytes can be measured simultaneously in 100 MUl of plasma from a single SEC separation. This methodology is particularly suited to simultaneous analysis of multiple proteins that may change their distribution to lipoproteins or alter their conformation, depending on factors that influence circulating lipoprotein size or composition. We observed changes in the distribution of exchangeable apolipoproteins following addition of recombinant apolipoproteins or interaction with exogenous compounds. While the cholesteryl ester transfer protein (CETP)-dependent formation of pre-beta-HDL was inhibited by the CETP inhibitors torcetrapib and anacetrapib, it was not reduced by the CETP modulator dalcetrapib. This finding was elucidated using this technique. PMID- 21971714 TI - Lipid body formation during maturation of human mast cells. AB - Lipid droplets, also called lipid bodies (LB) in inflammatory cells, are important cytoplasmic organelles. However, little is known about the molecular characteristics and functions of LBs in human mast cells (MC). Here, we have analyzed the genesis and components of LBs during differentiation of human peripheral blood-derived CD34(+) progenitors into connective tissue-type MCs. In our serum-free culture system, the maturing MCs, derived from 18 different donors, invariably developed triacylglycerol (TG)-rich LBs. Not known heretofore, the MCs transcribe the genes for perilipins (PLIN)1-4, but not PLIN5, and PLIN2 and PLIN3 display different degrees of LB association. Upon MC activation and ensuing degranulation, the LBs were not cosecreted with the cytoplasmic secretory granules. Exogenous arachidonic acid (AA) enhanced LB genesis in Triacsin C sensitive fashion, and it was found to be preferentially incorporated into the TGs of LBs. The large TG-associated pool of AA in LBs likely is a major precursor for eicosanoid production by MCs. In summary, we demonstrate that cultured human MCs derived from CD34(+) progenitors in peripheral blood provide a new tool to study regulatory mechanisms involving LB functions, with particular emphasis on AA metabolism, eicosanoid biosynthesis, and subsequent release of proinflammatory lipid mediators from these cells. PMID- 21971715 TI - From an epoxide monomer toolkit to functional PEG copolymers with adjustable LCST behavior. AB - The lower critical solution temperature (LCST) behavior of novel poly(ethylene glycol) (PEG)-based copolymers bearing multiple functional groups, obtained by anionic ring-opening (co)polymerization (AROP), has been investigated. Variable comonomer ratios of ethylene oxide (EO) and the corresponding oxiranes isopropylidene glyceryl glycidyl ether (IGG), ethoxyl vinyl glycidyl ether (EVGE), allyl glycidyl ether (AGE), or N,N-dibenzyl amino glycidyl (DBAG), particularly designed to implement functional groups at the PEG backbone, were found to influence the LCST behavior. Sharp transitions from translucent to opaque solutions, comparable to other well-established stimuli-responsive polymers, were observed at temperatures ranging from 9 to 82 degrees C. The influence of the side group hydrophobicity could be quantified by the comparison of the different copolymer systems observed. PMID- 21971716 TI - Heteroatomic Si/Ge Zintl clusters: single-crystal structure determination of Rb4[Si7.8Ge1.2](NH3)5 and [Rb([18]crown-6)Rb3][Si7.5Ge1.5](NH3)4. PMID- 21971717 TI - Two different techniques to facilitate reconstruction of the long incus process with bone cement: a feasibility study in human cadaveric temporal bones. AB - The purpose of this feasibility study was to evaluate two novel techniques facilitating bone cement repair of ossicular discontinuity between the incus and stapes. An isolated damage of the long incus process can be repaired using bone cement. However, bridging of a large gap between incus remnant and stapes head with bone cement is difficult, since viscous cement is not stable and the wet cement bridge may collapse. Ten fresh-frozen cadaveric human temporal bones were used. The long process of the incus was subtotally resected. A novel instrument and polylactide acid (PLA) scaffolds were applied to support ossicular reconstruction with bone cement. Stability of cement bridging was tested by checking for a round window reflex or motion of the stapes by palpating the malleus handle. Both the instrument as well as the PLA scaffolds were relatively easy to insert into the middle ear. However, bone cement adhered to the instrument irrespective of cement viscosity and contact time of the instrument with the ossicles. The bone cement plug had to be detached and sculptured. By contrast, PLA scaffolds could be used in a standardized manner and generated stable cement reconstructions. Curved PLA scaffolds were superior to straight ones. Initial results in cadaveric human temporal bones suggest that implantable PLA scaffolds might be suitable to support bone cement repair, even in very large defects of the long incus process. PMID- 21971718 TI - Comparison of tone burst versus logon stimulation for vestibular evoked myogenic potentials. AB - The following study has been carried out to compare the effectiveness of logon and tone burst acoustic stimulation to elicit vestibular evoked myogenic potential (VEMP) responses. The methods and the subjects include 31 healthy adult volunteers (62 ears) who were enrolled in this study. Two different acoustic stimuli, logon (L-VEMP) and tone burst (T-VEMP), were used to elicit VEMP responses in each subject. Bilateral recordings with simultaneous binaural acoustic stimulations were used during VEMP recordings. During the recording period, the subjects were in supine position with their head elevated. The results observed were that the response rate of p1n1 wave was 91.9% for L-VEMP and 88.7% for T-VEMP. The response rate of n2p2 wave was 80.6% for L-VEMP, and 75.8% for T-VEMP. There were no significant differences between the two groups with respect to the latencies of p1, n1, n2 and p2, p1n1 and n2p2 interval, and p1n1 and n2p2 amplitude. The conclusion was that there was no difference between logon and tone burst stimulation with respect to VEMP response rates and VEMP parameters. Therefore, they are not superior to each other. PMID- 21971719 TI - Detection of passive movement of the arytenoid cartilage in unilateral vocal-fold paralysis by laryngoscopic observation: useful diagnostic findings. AB - In a previous study of patients with unilateral vocal-fold paralysis (UVFP), three-dimensional computed tomography (3DCT) revealed passive movement during phonation, with the arytenoid cartilage on the paralyzed side pushed to the unaffected side and deviated upwards. The present work compares the 3DCT findings with those obtained by 2-dimensional endoscopy to visualize the vertical passive movement of the arytenoid cartilage. The study population consisted of 23 patients with UVFP and two with laryngeal deviation but normal movement of the vocal folds. Two endoscopic findings represented cranial deviation during phonation: posterior deviation of the arytenoid hump and lateral deviation of the muscular process. These two findings were classified into four grades, ranging from 0 (normal) to 3 (severe). Cranial displacement detected by 3DCT was also classified into four grades. Significant correlations were found between the 3DCT determined grade of cranial displacement of the arytenoid cartilage and the grade assigned based on the two endoscopic findings. Moreover, lateral deviation of the muscular process was more significantly correlated with 3DCT grade than with endoscopic grade. Thus, endoscopic findings may be useful in the diagnosis of vocal-fold paralysis, and passive lateral deviation of the muscular process as an indicator of UVFP. PMID- 21971720 TI - Mechanical thrombectomy compared to local-intraarterial thrombolysis in carotid T and middle cerebral artery occlusions: a single center experience. AB - PURPOSE: The aim of the study was to examine the effects of mechanical thrombectomy using the Solitaire stent in patients with thromboembolic occlusions of the intracranial carotid artery bifurcation (carotid T) or middle cerebral artery (MCA) and to compare the results with a historical cohort treated with local intraarterial thrombolysis using urokinase. METHODS: The time intervals from stroke onset to treatment, recanalization rates, occlusion sites, recanalization times and functional outcomes on the modified Rankin scale at 3 months in 25 patients treated with the Solitaire stent between 2010 and 2011 were evaluated. The data were compared with those of a historical cohort of 62 patients treated with local intraarterial thrombolysis between 1992 and 2001. RESULTS: A total of 15 out of 25 (60%) patients treated with mechanical thrombectomy and 25 out of 62 (40%) treated with local intraarterial thrombolysis achieved a modified Rankin score of <=2 (p = 0.07). Occlusion sites, intervals from stroke onset to treatment and rates of parenchymal hematomas, 3 out of 25 (12%) versus 8 out of 62 (13%), were similar in both cohorts while the recanalization rate was significantly higher, 22 out of 25 (88%) versus 33 of 62 (53%), in the mechanical thrombectomy group (p <= 0.01). CONCLUSION: The data show that mechanical thrombectomy is superior to local intraarterial thrombolysis with respect to the recanalization rate in patients with thrombeoembolic carotid T or MCA occlusions. PMID- 21971721 TI - Coordination-driven self-assembly of 2D-metallamacrocycles using a shape selective Pt(II)2-organometallic 90 degrees acceptor: design, synthesis and sensing study. AB - Synthesis of a series of two-dimensional metallamacrocycles via coordination driven self-assembly of a shape-selective Pt(II)(2)-molecular building unit incorporating carbazole-ethynyl functionality is described. An equimolar (1 : 1) combination of a Pt(II)(2)-organometallic 90 degrees acceptor, 1, with rigid linear ditopic donors (L(a) and L(b)) afforded [4 + 4] self-assembled octanuclear molecular squares, 2 and 3, in quantitative yields, respectively [L(a) = 4,4' bipyridine; L(b) = trans-1,2-bis(4-pyridyl)ethylene]. Conversely, a similar treatment of 1 with an amide-based unsymmetrical flexible ditopic donor, L(c), resulted in the formation of a [2 + 2] self-sorted molecular rhomboid (4a) as a single product [L(c) = N-(4-pyridyl)isonicotinamide]. Despite the possibility of several linkage isomeric macrocycles (rhomboid, triangle and square) due to the different connectivity of L(c), the formation of a single and symmetrical molecular rhomboid (4a) as the only product is an interesting observation. All the self-assembled macrocycles (2, 3 and 4a) were fully characterized by multinuclear NMR ((1)H and (31)P) and ESI-MS analysis. Further structural insights about the size and shape of the macrocycles were obtained through energy minimization using density functional theory (DFT) calculations. Decoration of the starting carbazole building unit with Pt-ethynyl functionality enriches the assemblies to be more pi-electron rich and luminescent in nature. Macrocycles 2 and 3 could sense the presence of electron deficient nitroaromatics in solution by quenching of the initial intensity upon gradual addition of picric acid (PA). They exhibited the largest quenching response with high selectivity for nitroaromatics compared to several other electron deficient aromatics tested. PMID- 21971722 TI - Balance and aerobic capacity of independent elderly: a longitudinal cohort study. AB - OBJECTIVE: To evaluate the variation in aerobic capacity and postural balance of independents elderly for a period of three years. METHODS: The aerobic capacity of the volunteers was assessed using a six minutes walk test (6MWT), the postural balance was assessed using the Berg Balance Scale (BBS), the number of falls was self-reported and physical activity level was assessed using the International Physical Activity Questionnaire (IPAQ - long version). Evaluations undertaken in 2008 were compared to those performed in 2005. RESULTS: There were no differences in balance and number of falls between 2008 and 2005 (p>0.05). There was a decrease in aerobic capacity over time of 52.46+/-8.4 meters walked. The IPAQ showed an increase in physical activity on the second evaluation (83.3%). CONCLUSION: The present study demonstrated that balance, evaluated using BBS did not change in the active independent elderly for a period of three years. However, over the there year period there was a decrease in aerobic capacity evaluated using the 6MWT. PMID- 21971723 TI - Influence of change in lateral decubitus on pulmonary aerosol deposition. AB - BACKGROUND: The lateral decubitus position leads to the greatest changes in regional pulmonary ventilation and is used in respiratory physical therapy routines. OBJECTIVES: To evaluate the influence of the lateral decubitus position on the pulmonary deposition of inhaled radioaerosol particles in young people and report the effects of the decubitus position on routine therapy. METHODS: Eight healthy male volunteers, mean age 23.6+/-2.5 years, were included in a randomized study in two phases. In the first phase, aerosol was inhaled for nine minutes in a randomly-selected lateral decubitus position and after an interval of 5 to 7 days, the second phase was conducted. Pulmonary scintigraphy was carried out by inhalation of 25 mCi of 99mTc-DTPA. Following inhalation, images were acquired with scintillation cameras and regions of interest (ROI) were investigated in the longitudinal and cross-sectional divisions of the lungs. Statistical analysis included a paired Student's t-test with a significance level of p<=0.05. RESULTS: Inhalation in the right lateral decubitus position presented higher counts (p<=0.04) in posterior ROI of the right lung than in the posterior ROI of the left lung. In the left lateral decubitus position, the count was higher in the left lung (p<=0.02) than in the posterior ROI of the right lung. CONCLUSIONS: The deposition of aerosol particles during inhalation was position-dependent in the two phases of the study, which confirms the validity of technical and therapeutic resources based on the physiology of position-dependent ventilation and suggests that body positioning can be used to advantage in routine therapy. PMID- 21971724 TI - Anthropometric and musculoskeletal assessment of patients with Marfan syndrome. AB - BACKGROUND: Marfan syndrome (MS) is an autosomic dominant condition of the connective tissue that involves the ocular, cardiovascular and musculoskeletal systems. MS is caused by mutations in the fibrillin-1 gene, leading to joint ligaments flaccidity, joint hypermobility and an overgrowth of the long bones. OBJECTIVES: The aim of the present study was to assess anthropometry, musculoskeletal alterations and the prevalence of physical therapy treatments among patients with MS. METHODS: Twenty-six patients were included in this study [17 females (age: 13.23+/-2.77 years; body mass 51.5+/-24-68 Kg; height 1.70+/ 1.40-1.81 m; arm span: 1.73+/-0.12 m) and 9 males (age: 14.44+/-2.18; body mass: 61.0+/-42-72 Kg; height: 1.83+/-1.66-1.97 m; arm span: 1.93+/-0.13 m)]. Anthropometric measurements and musculoskeletal abnormalities were determined in a standardized fashion: pectus and scoliosis were assessed through radiography and angulation (a) of the scoliosis curve using the Cobb method; arachnodactyly was assessed through the thumb sign and Walker-Murdoch test and dolichostenomelia was assessed by arm span in relation to height. Patients also responded to a questionnaire addressing participation in physical therapy. RESULTS: In comparison to values estimated for the Brazilian population, mass and height were greater among the patients with MS (females: p=0.001 e p<0.0005 e males p=0.019 e p=0.0001, respectively). The following musculoskeletal abnormalities were found: pectus in 3 patients (11%), pectus and scoliosis in 19 (73%), dolichostenomelia in 11 (42%) and arachnodactyly in 21 (80%). Eleven patients (42%) with MS had previously undergone physical therapy. CONCLUSIONS: Patients with MS exhibit altered musculoskeleto and anthropometry and have infrequent physical therapy treatment. PMID- 21971725 TI - Anti-inflammatory action of the Ovis aries lipidic fraction associated to therapeutic ultrasound in an experimental model of tendinitis in rats (Rattus norvegicus). AB - BACKGROUND: Studies have demonstrated the beneficial effects of topical application of fatty acids as healing agents. The lipid fraction of Ovis aries have an anti-inflammatory action that accelerates the healing process. Ultrasound increases blood flow and the extensibility of collagen structures and tendons. OBJECTIVES: To assess the anti-inflammatory action of the Ovis aries lipid fraction associated to pulsed therapeutic ultrasound and friction in an induced tendinitis model. METHODS: Fifty Wistar rats were divided into four groups: control that consisted of Ovis aries gel for topical use; pulsed ultrasound plus oil free sterile lotion; pulsed ultrasound plus Ovis aries gel; and oil free sterile lotion for topical use alone. To induce tendinitis a 10 uL intratendinous injection of collagenase was injected into the right Achilles tendon of rats. Treatment consisted of daily applications of ultrasound using the following parameters: 10% pulsed mode, 10% pulsed frequency of 1 MHz and intensity of 0.5 W/cm2 for seven or fourteen days. RESULTS: After 7 days of treatment, only the Ovis aries plus ultrasound group showed statistically significant difference when compared to the control group.The variation in the number of inflammatory cells on animals treated for fourteen days for the control, ultrasound plus oil free, ultrasound plus Ovis aries, Ovis aries plus massage and massage plus oil free groups were statistically significant different, p<0.01. It was observed in animals treated for seven days that the ultrasound plus Ovis aries group was statistically significant better than the control group, p<0.05. CONCLUSION: It can be concluded that treatment using ultrasound plus Ovis aries is more effective than other treatments as it produces significantly better reduction on the number of inflammatory cells at 7 and 14 days. PMID- 21971726 TI - Impact of resistance exercise program on functional capacity and muscular strength of knee extensor in pre-frail community-dwelling older women: a randomized crossover trial. AB - BACKGROUND: Frailty syndrome in elderly people is characterized by a reduction of energy reserves and also by a decreased of resistance to stressors, resulting in an increase of vulnerability. OBJECTIVE: The aim of this study was to verify the effect of a muscle-strengthening program with load in pre-frail elder women with regards to the functional capacity, knee extensor muscle strength and their correlation. METHODS: Thrity-two pre-frail community-dwelling women participated in this study. Potential participants with cognitive impairment (MEEM), lower extremities orthopedic surgery, fractures, inability to walk unaided, neurological diseases, acute inflammatory disease, tumor growth, regular physical activity and current use of immunomodulators were excluded. All partcipants were evaluated by a blinded assessor using: Timed up and go (TUG), 10-Meter Walk Test (10MWT) and knee extensor muscle strength (Byodex System 3 Pro(r) isokinetic dynamometer at angular speeds of 60 and 180(0)/s). The intervention consisted of strengthening exercises of the lower extremities at 70% of 1RM, three times/ week for ten weeks. The statistical analysis was performed using the ANOVA and Spearman tests RESULTS: After the intervention, it was observed statistical significance on the work at 180(0)/s (F=12.71, p=0.02), on the power at 180(0)/s (F=15.40, p=0.02) and on the functional capacity (TUG, F=9.54, p=0.01; TC10, F=3.80, p=0.01). There was a good negative and statistically significant correlation between the TUG and work at 60(0)/s, such as the TUG and work at 180(0)/s (r=-0.65, p=0.01; r=-0.72, p=0.01). CONCLUSION: The intervention improved the muscular power and the functional capacity. The increase of the power correlated with function, which is an important variable of the quality of life in the pre-frail elders. Article registered in the ISRCT register under number ISRCTN62824599. PMID- 21971727 TI - My manuscript was rejected, and now? PMID- 21971728 TI - Trajectories of body image and sexuality during the first year following diagnosis of breast cancer and their relationship to 6 years psychosocial outcomes. AB - We examined degree and determinants of change in body image and sexuality over the first year following breast cancer diagnosis to differentiate body image and sexuality trajectories, and then explored if differences in trajectories predicted 6 years' psychosocial outcomes. 363/405 (90%) Chinese women receiving surgery for BC were assessed at 5-days (Baseline), 1-month, 4-months, and 8 months post-surgery. Psychological distress, treatment decision making (TDM) difficulties, satisfaction with treatment outcome, optimism, and self-efficacy were assessed at Baseline. Self-image and sexuality were recorded at each follow up assessment. Latent growth mixture modeling identified trajectories of self image and sexuality. Multinominal logistic regression identified factors predicting trajectory patterns. Six years later 211/363 (58%) of the original patients were successfully traced and their psychosocial status assessed. Three distinct trajectories of self-image and sexuality were identified: high-stable, recovery, and high-deteriorating. Most women (64% self-image; 58% sexuality) showed stable levels of self-image and sexuality scores. TDM difficulties, satisfaction with treatment outcomes, physical symptom and psychological distress predicted trajectory patterns. Self-image trajectories over the first year diagnosis predicted 6-years psychosocial outcomes. Women with high-stable level of self-image had the best 6-year self-image and sexuality; women with initial low level of self-image had significantly greater long-term psychological distress. Low TDM difficulties and high treatment outcome satisfaction predicted high and stable self-image and sexuality. Type of surgery showed little impacts on self-image and sexuality. Self-image during acute illness phase predicted long term outcomes. Interventions should focus on minimizing self-image decrement. PMID- 21971729 TI - Prognostic value of chemotherapy-induced neutropenia in early-stage breast cancer. AB - Neutropenia is one of the most important dose-limiting toxicities and often the reason for dose reduction. In this study we aimed to assess whether chemotherapy induced neutropenia could be a marker of efficacy and associate with increased survival. Data from a retrospective survey for early breast cancer patients in our hospital were reviewed. Three hundred and thirty-five patients who had been treated with six cycles of cyclophosphamide, epirubicin, and fluorouracil (CEF) were studied. The association between chemotherapy-induced neutropenia and overall survival (OS) was assessed. According to a multivariate Cox model with time-varying covariates, hazard ratios of death were 0.434 (95% confidence interval (CI), 0.298-0.634; P < 0.001) for patients with mild neutropenia, and 0.640 (95% CI, 0.42-0.975; P = 0.038) for those with severe neutropenia. Neutropenia occurring in early breast cancer patients is an independent predictor of increased survival. These findings suggest that neutropenia in patients who receive chemotherapy is strongly associated with a better prognosis. PMID- 21971730 TI - Bone marrow versus sentinel lymph node involvement in breast cancer: a comparison of early hematogenous and early lymphatic tumor spread. AB - The early spread of tumor cells in primary breast cancer patients may occur either through lymphatic or hematogenous dissemination. Lymph node (LN) status and presence of disseminated tumor cells (DTC) in bone marrow (BM) are independent predictors of poor outcome. It is unknown which factors determine one or the other route of tumor cell spread and whether lymphatic and hematogenous tumor cell dissemination are two independent processes. This study is aimed to compare the DTC status in clinically node-negative (N0) breast cancer patients with their sentinel LN status and to investigate predictors of BM and LN involvement. The DTC status of 1,345 clinically N0 breast cancer patients who underwent SLN biopsy during initial surgery was investigated. BM and LN status were compared and predictors of hematogenous and lymphatic tumor cell spread were investigated. DTCs were present in the BM of 181 (13%) patients. LN involvement was found in 348 (26%) patients. There was no correlation between LN and BM status: 137 of 997 nodal-negative patients (14%) had BM involvement and 44 of 348 nodal-positive patients (13%) were positive for DTCs (P = 0.649). The presence of DTCs was not influenced by tumorbiological factors. Conversely, a high correlation between nodal status and tumor size, histology, ER-status and lymph vessel invasion was found. Hematogenous and lymphatic tumor spread seem to be because of independent pathways of cancer progression. PMID- 21971731 TI - Pneumatic retinopexy for retinal detachment associated with choroidal coloboma. AB - PURPOSE: To report a case of retinal detachment in an eye with choroidal coloboma treated with pneumatic retinopexy and laser. METHODS: Case report. RESULTS: A 34 year-old woman who had had poor vision in her left eye since early childhood and high myopia in her right eye complained a sudden deterioration of vision in her left eye for 3 days. Fundus examination of the left eye showed a large choroidal coloboma, extending to the disc margin from 5-8 o'clock inferiorly and above the inferotemporal arcade, excluding the fovea and the parafovea. Superotemporal bullous detachment of the retina was also observed, including the macula. The patient underwent a pneumatic retinopexy with SF(6) gas (0.5 cc) injection into the vitreous cavity. The following day laser was applied around the margin of the choroidal coloboma. Three months later, visual acuity was 20/200 and fundus examination disclosed a completely attached retina. CONCLUSIONS: This case demonstrates the feasibility of using pneumatic retinopexy in selected cases. PMID- 21971732 TI - Amniotic membrane transplantation in corneal melting after anterior lamellar keratoplasty assisted by femtosecond laser in children. AB - PURPOSE: To evaluate the efficacy of amniotic membrane transplantation in lamella melting after anterior lamellar keratoplasty (ALK) assisted by femtosecond laser in a pediatric patient. METHODS: An 11-year-old girl with progressive keratoconus underwent ALK assisted by femtosecond laser on the right eye. The surgical procedure was performed under general anesthesia. The 60-KHz IntraLase femtosecond laser (Abbott Medical Optics) created both the donor (thickness 350 um; diameter 8.1 mm; side cut 70 degrees ) and recipient (thickness 260 um; diameter 8.0 mm; side cut 70 degrees ) lamellae. The recipient lamella was then gently removed and donor was fitted into place and sutured using 4 interrupted sutures added to a running suture in nylon 10-0. The surgery was uneventful. Two months after surgery, a lamella melting was observed. One month after topical steroid treatment, amniotic membrane transplantation was performed. RESULTS: When lamella melting was observed, the best-corrected visual acuity (BCVA) was 0.1 and 0.5 with foramen and no inflammatory reaction in the anterior chamber was reported. Eleven months after amniotic membrane transplantation, BCVA was 0.9 and no visual acuity increase was recorded with foramen. CONCLUSIONS: Our findings show that amniotic membrane transplantation could be considered in lamella melting after ALK assisted by femtosecond laser in children. PMID- 21971733 TI - Psychometric properties of the Greek NEI-RQL-42. AB - PURPOSE: To evaluate the psychometric properties of the Greek National Eye Institute Refractive Error Quality of Life Questionnaire (NEI-RQL-42). METHODS: We developed the Greek version of the instrument using forward and backward translation. To examine reliability, Cronbach alpha for each subscale was used as an index of internal consistency. Test-retest reliability was evaluated with intraclass correlation coefficients (ICC). Regarding construct validity, both convergent and discriminant validities were calculated by means of multi-trait analysis. Furthermore, the instrument was evaluated by Rasch analysis, as well. RESULTS: Three patient groups were studied (emmetropes (n = 20), myopes (n = 41), and hyperopes (n = 18)). Emmetropes scored significantly better in the majority of subscales, while myopes scored better than hyperopes in clarity of vision (p = 0.012), near vision (p<0.001), and satisfaction with correction (p = 0.001). Cronbach alpha ranged from 0.490 (glare) to 0.948 (expectations), with most subscales having high internal consistency. The ICCs ranged from 0.76 to 0.93 for all subscales. All items passed the convergent and discriminant validity tests. Strong correlations were detected between uncorrected visual acuity and near vision, expectations, activity limitations, dependence on correction, worry, and suboptimal correction subscales. Rasch analysis revealed potential weaknesses of the instrument that are associated with the assumptions of the model itself. Specifically, 3 items and 17.5% of the participants fell outside the tolerance box. Moreover, principal component analysis indicated average unidimensionality for the instrument. CONCLUSIONS: Traditional validation methods indicate that the Greek NEI-RQL-42 scale has adequate psychometric properties for comparative studies in local populations. Rasch analysis indicates significant misfits to the model that should be taken into consideration and evaluated in future studies. These misfits might reflect inherent weaknesses of the original NEI-RQL-42 and not of its adaptation to Greek norms. PMID- 21971734 TI - Corticosteroid-use in primary and secondary brain tumour patients: a review. AB - Corticosteroids have been effective in the management of cerebral oedema, in the context of brain tumours, for many decades. Though their effectiveness is well established, this needs to be balanced against their potential to cause significant side effects. There is currently little consensus in the literature about how this should be done. This article reviews the literature, specifically in relation to the role of corticosteroids in primary and secondary brain tumour patients. Areas reviewed include corticosteroid pharmacology, indications, mechanism of action, toxicity profile, prescribing practices, and corticosteroid sparing agents. PMID- 21971736 TI - Ion channels in pediatric CNS Atypical Teratoid/Rhabdoid Tumor (AT/RT) cells: potential targets for novel therapeutic agents. AB - The central nervous system Atypical Teratoid/Rhabdoid Tumor (CNS AT/RT) is a highly malignant neoplasm that commonly affects infants and young children, and has an extremely poor prognosis. Recently, a small subset of ion channels have been found to be over-expressed in a variety of malignant cells, thus emerging as potential therapeutic targets for difficult to treat tumors. We have studied the electrophysiological properties of AT/RT cell lines with particular attention to cell volume sensitive ion channels (VSC). This class of membrane proteins can play a fundamental role in cellular processes relevant to tumor development. We have found that chloride selective VSCs are particularly active in AT/RT cell lines, compared to non-tumor cells. We evaluated specific inhibitors for activity against chloride selective VSCs and consequently for their ability to inhibit the growth and survival of AT/RT cells in vitro. The results demonstrated that the extent of volume sensitive membrane current inhibition by these agents was correlated with their potency in AT/RT cell growth inhibition in vitro. In addition, we showed that ion channel inhibition enhanced the activity of certain anti-neoplastic agents, suggesting its value in effective drug combination protocols. Results presented provide preliminary in vitro data for possible evaluation of distinct ion channels as plausible therapeutic targets in the treatment of AT/RT. PMID- 21971738 TI - Audiological investigation of otitis media in children with atopy. AB - Otitis media (OM) describes an inflammatory process within the middle ear space that is generally associated with accumulation of fluid and that may lead to hearing loss, learning difficulties, and delays in language development. The pathogenesis of OM is multifactorial, involving the adaptive and native immune system, eustachian tube dysfunction, viral and bacterial load, and genetic and environmental factors. The involvement of IgE-mediated allergic reactions in the pathogenesis of OM has been suggested by clinical observations of a high prevalence of OM among patients with allergies. Evidence from studies involving tympanometric measurements, audiometric measurements, and otoscopic examination confirms the role of atopy in the development and persistence of OM. PMID- 21971737 TI - Cerebrospinal fluid stimulates leptomeningeal and meningioma cell proliferation and activation of STAT3. AB - The role of cerebrospinal fluid (CSF) in the pathogenesis of meningiomas is unknown. Cell cultures from three human leptomeninges, five WHO grade I and seven grade II meningiomas were treated with remnant CSF from 22 patients with no central nervous system disease and normal cell indices. Cells were evaluated by CyQUANT for DNA synthesis/cell proliferation and by western blots for phosphorylation/activation of growth regulatory pathways activated in meningiomas including JAK1-STAT3, MEK1-p44/42MAPK, Akt-mTOR and Rb. Analysis of Caspase 3 activation and survivin was also performed. Finally, the effects of PDGF neutralizing antibody and cucurbitacin, a STAT3 inhibitor on CSF stimulation were tested. Compared to controls and the mitogen PDGF-BB, various CSF samples significantly stimulated DNA synthesis/cell proliferation in 20 and 22 week leptomeningeal cultures and all of the grade I and II meningioma cells tested. Collectively CSF samples, from multiple different patients, stimulated DNA synthesis in tests of 23 of 32 grade I and 18 of 28 grade II meningioma cells. CSF stimulated phosphorylation/activation of STAT3 and reduced p44/42 MAPK in the leptomeningeal, all three grade I and 1 of three grade II meningioma cells. CSF did not affect Caspase 3 activity or survivin levels. PDGF neutralizing antibody had no effect on CSF stimulation but cucurbitacin blocked PDGF and CSF stimulation. While there are limitations to the CSF available since they were not from "normal" volunteers, the studies suggest that, in some settings, CSF is potentially mitogenic to leptomeningeal and meningioma cells and may act, in part, via activation of STAT3. PMID- 21971739 TI - Computed tomography angiography (CTA) to prove circulatory arrest for the diagnosis of brain death in the context of organ transplantation. AB - QUESTION UNDER STUDY: For the determination of brain death (BD) in potential organ donors, confirmatory tests that show cessation of cerebral circulation are used in many countries. Conventional angiography is considered the golden standard among these ancillary examinations. In recent years other angiographic techniques such as CT angiography (CTA) have been increasingly employed to establish the diagnosis of BD. We report our experience with CTA in this setting. MATERIAL AND METHODS: From 2007 to 2010, 29 patients were examined in order to determine BD using CTA. The studies consisted of an unenhanced head scan, a CT angiogram of the brain supplying vessels in the head and neck and a second head scan 80 seconds after contrast injection (venous phase). The studies were retrospectively re-evaluated by two experienced neuroradiologists according to the criteria accepted by the Swiss Academy of Medical Sciences. RESULTS: In 22 patients, cessation of cerebral circulation was confirmed in the venous phase CT. In seven patients, cessation of brain circulation was not confirmed due to residual contrast enhancement in the relevant cerebral vessels, i.e. the M4 segments of the middle cerebral artery and/or the internal cerebral veins. In these patients, clinical re-evaluation after a minimum of six hours confirmed the diagnosis of BD. Using the clinical examination as the "golden standard," CTA achieved a sensitivity of 75.9%. CONCLUSION: CTA is a useful additional tool for the confirmation of the diagnosis of brain death. Pooling of contrast in the relevant cerebral vessels, however, can be detected in up to 25% of CTAs in clinically brain dead patients. PMID- 21971740 TI - Identification of cervicothoracic intervertebral spaces by surface landmarks and ultrasound. AB - PURPOSE: Precise localization of the cervicothoracic vertebral levels is essential for accurate placement of epidural catheters. Previous studies have demonstrated that anesthesiologists are inaccurate when using surface anatomy to locate lumbar vertebral levels. Our study was designed to determine the agreement between anatomical landmarks and the ultrasound technique in identifying the T7-8 and C7-T1 intervertebral spaces. METHODS: Adult healthy volunteers were assessed for the identification of cervicothoracic intervertebral spaces, initially in the anatomic position (AP)-upright, back straight, arms at the sides, and palms forward and then in the epidural position (EP) routinely used for epidural placement-seated, back arched, neck flexed, and arms across the chest. The T7 and C7 spinous processes were identified by one investigator using the inferior tip of the scapula and the vertebra prominens, respectively, as landmarks. Ultrasound was then used by a second investigator to identify the intervertebral spaces corresponding to the previously marked levels. RESULTS: Fifty-five volunteers (23 males, 32 females) were recruited. The T7-8 intervertebral space determined by ultrasound coincided with the landmark findings in the AP and in the EP in 18% and 36% of the cases, respectively. The C7-T1 interspace identified by ultrasound corresponded with the surface landmarks in the AP and in the EP in 53% and 58% of the cases, respectively. In most cases, when the surface landmark and ultrasound findings of T7-8 did not agree, the surface landmark identified a lower interspace than ultrasound. CONCLUSION: Identification of cervicothoracic intervertebral spaces by surface landmarks corresponded poorly with their identification using ultrasound. However, compared with the upright position, agreement in identifying the T7-8 interspace improved in the epidural position. PMID- 21971741 TI - Bilateral thoracic sympathetic block for refractory polymorphic tachycardia. AB - INTRODUCTION: Extensive evidence has established a link between sympathetic nervous system hyperactivity, ventricular arrhythmias, and sudden cardiac death. For this reason, cardiac sympathectomy is often beneficial in the treatment of patients at high risk for ventricular ectopy, although it involves an invasive procedure associated with potential morbidity. We report a case in which we used guided lytic thoracic sympathetic block in a patient with underlying cardiomyopathy and refractory polymorphic ventricular tachycardia. CLINICAL FEATURES: A 74-yr-old African American male with ischemic cardiomyopathy presented with refractory episodes of ventricular tachycardia despite maximal medical therapy involving antiarrhythmic drugs and previous interventions, including endovascular epicardial ablation and open cryoablation via sternotomy. During his inpatient admission, the patient developed sustained ventricular tachycardia associated with cardiac depression requiring vasopressors. An open thoracoscopic sympathectomy was considered as a possible treatment, but in our view, the patient would not tolerate this procedure. As an alternative, the pain medicine team successfully performed a lytic thoracic sympathetic block. Subsequently, the patient demonstrated a period of clinical improvement with no apparent morbidity related to the procedure. CONCLUSION: Lytic thoracic sympathetic blockade is a novel technique for the treatment of sympathetically mediated ventricular tachycardia, and it is less invasive than other types of cardiac sympathectomy. Additional studies are required to evaluate this treatment as a viable alternative in patients at high risk for ventricular ectopy. This report suggests the feasibility of this approach and the potential for minimal morbidity in cases of refractory ventricular arrhythmias. PMID- 21971742 TI - No evidence for superiority of air or oxygen for neonatal resuscitation: a meta analysis. AB - PURPOSE: The aim of this meta-analysis was to re-evaluate the evidence in favour of oxygen or room air as the initial gas mixture for neonatal resuscitation in terms of the following outcomes: death, hypoxic/ischemic encephalopathy, need for tracheal intubation, and APGAR score-Appearance (skin color), Pulse (heart rate), Grimace (reflex irritability), Activity (muscle tone), and Respiration-at five minutes. METHODS: A search with no language restriction for all available controlled clinical trials (CCT) was conducted in PUBMED, Cochrane Central Register of Controlled Trials, and EMBASE. Data were extracted independently by the two investigators. RESULTS: Eight CCTs were retained for analysis. They included 1,500 patients, 772 in the oxygen group and 728 in the air group. The evidence is based mainly on quasi-randomized studies (1,311/1,500) with unblinded resuscitators (1,421/1,500). The expertise/training of the resuscitators was unspecified for four of the eight studies. The risk ratio (RR) for death was 1.35 (95% confidence intervals [CI] = 0.97 to 1.88; P = 0.08; I-squared 0%). The RR for hypoxic/ischemic encephalopathy was 1.03 (95% CI = 0.86 to 1.23; P = 0.74; I squared 0%). The RR for requiring a tracheal intubation was 0.85 (95% CI = 0.69 to 1.05 [random effects model]; P = 0.12; I-squared = 9.51%). CONCLUSIONS: The literature is insufficient to make any statement regarding the superiority of oxygen or room air as the initial gas mixture for neonatal resuscitation. PMID- 21971743 TI - Effects of sitting up for five minutes versus immediately lying down after spinal anesthesia for Cesarean delivery on fluid and ephedrine requirement; a randomized trial. AB - BACKGROUND: Patient position after spinal anesthesia has had variable effects on blood pressure and ephedrine requirements. The aim of this study was to determine the effects that sitting the patient up for five minutes after spinal anesthesia would have on intraoperative fluid and ephedrine requirements. METHODS: The study included 120 women at term gestation who were scheduled for Cesarean delivery under spinal anesthesia. After anesthetic administration, the women were randomized either to sit up for five minutes then lie down (Group S) or to lie down immediately (Group L) to a tilted supine position. A blinded observer recorded sensory block level, systolic blood pressure, heart rate, ephedrine and fluid requirements, adverse events, and time to motor recovery (modified Bromage score of 2). RESULTS: Group S had a lower intraoperative sensory block height than Group L [T4 (1) vs T2 (1), respectively; P < 0.001]; Group S also required less ephedrine (8% vs 47%, respectively; P < 0.001), received less fluid [709 (59) mL vs 789 (90) mL, respectively; P < 0.001], and experienced less nausea and vomiting (5% vs 22%, respectively; P = 0.014) and shortness of breath (3% vs 28%, respectively; P < 0.001) intraoperatively. In Group S, the odds of requiring ephedrine were 0.09 compared with 0.89 in Group L (odds ratio 0.10). There were no differences in systolic blood pressure (P = 0.127) or heart rate (P = 0.831) over time between groups. Time to a modified Bromage score of 2 was longer in Group S than in Group L [101 (15) min vs 88 (14) min, respectively; P < 0.001]. CONCLUSIONS: Sitting the patient up for five minutes rather than laying the patient down immediately after spinal anesthesia for Cesarean delivery decreased intraoperative sensory block height, ephedrine and fluid requirements, and intraoperative nausea, vomiting, and shortness of breath without affecting systolic blood pressure or the success of the anesthetic. However, the method resulted in delayed postoperative motor recovery. PMID- 21971744 TI - A possible explanation for cricoid pressure to improve the laryngeal view with the Truview Evo2TM laryngoscope. PMID- 21971745 TI - Role of gap junctions in chronic pain. AB - Gap junctions are specialized transmembrane channels that allow rapid electrical signalling and direct intercellular communication for maintenance and coordination of normal cellular activities and homeostasis. Although gap junction channels in the nervous system mediate intercellular coupling between glial cells and between neurons, they also contribute to the spread of secondary damage and inflammation under pathological conditions. There is now evidence of the involvement of gap junctions in chronic pain caused by nervous system damage or tissue inflammation. In this Mini-Review, we highlight recent studies demonstrating the dynamic plasticity of gap junctions in response to nervous system injury and the effects of gap junction blockade on neuronal survival and modulation of pain in animal models of neuropathic and inflammatory pain. The involvement of dorsal root ganglia and spinal cord gap junctions in mediating chronic pain and the potential for targeting connexins as a novel modality for the treatment of intractable pain syndromes arising from nervous system injury and disorders are discussed. PMID- 21971746 TI - Expression analysis of a heat-inducible, Myo-inositol-1-phosphate synthase (MIPS) gene from wheat and the alternatively spliced variants of rice and Arabidopsis. AB - Molecular dissection and a deeper analysis of the heat stress response mechanism in wheat have been poorly understood so far. This study delves into the molecular basis of action of TaMIPS, a heat stress-inducible enzyme that was identified through PCR-select subtraction technology, which is named here as TaMIPS2. MIPS (L-Myo-inositol-phosphate synthase) is important for the normal growth and development in plants. Expression profiling showed that TaMIPS2 is expressed during different developing seed stages upon heat stress. Also, the transcript levels increase in unfertilized ovaries and significant amounts are present during the recovery period providing evidence that MIPS is crucial for its role in heat stress recovery and flower development. Alternatively spliced forms from rice and Arabidopsis were also identified and their expression analysis revealed that apart from heat stress, some of the spliced variants were also inducible by drought, NaCl, Cold, ABA, BR, SA and mannitol. In silico promoter analysis revealed various cis-elements that could contribute for the differential regulation of MIPS in different plant systems. Phylogenetic analysis indicated that MIPS are highly conserved among monocots and dicots and TaMIPS2 grouped specifically with monocots. Comparative analyses was undertaken by different experimental approaches, i.e., semi-quantitative RT-PCR, quantitative RT-PCR, Genevestigator as a reference expression tool and motif analysis to predict the possible function of TaMIPS2 in regulating the different aspects of plant development under abiotic stress in wheat. PMID- 21971747 TI - Antioxidant activity of flavonoids evaluated with myoglobin method. AB - Antioxidant activities of four flavonoids (rutin, quercetin, luteolin, and kaempferol) and two non-flavonoids (chlorogenic acid and pyrocatechol) against four reactive oxygen species (ROS) have been measured with a myoglobin method developed by our group. The myoglobin method uses the absorbance changes of myoglobin (a probe molecule) due to the reaction with the ROS as an indicator for the antioxidant activity measurement. Myoglobin protective ratio (MPR) was defined to express the antioxidant activities of the specimens. Antioxidant activities against hypochlorite ion, hydroxyl radical, peroxyl radical, and peroxynitrite were measured with the myoglobin method. The antioxidant activities were comprehensively evaluated by plotting MPR against four ROS and vitamin C equivalent concentration evaluated by DPPH quenching method in 5-axe cobweb charts. The four flavonoids show a very similar pattern in the 5-axe cobweb charts, while the patterns of two non-flavonoids are quite different from that of the flavonoids. This procedure combining the myoglobin method with the cobweb charts is useful in the evaluation of antioxidant activities of plant-derived food, and also can be extended to monitor antioxidant condition of media for plant cell cultures. PMID- 21971748 TI - Dendritic cells transfected with lentiviral vector-encoding hTERT peptide augment antitumor T cell response in vitro. AB - HIV-1 derived lentiviral vectors (LVs) have emerged as a powerful tool for gene delivery. hTERT is an ideal tumor-associated antigen with which to develop a potential dendritic cell (DC) vaccine. The purpose of this study was to construct a recombinant lentivirus vector of the hTERT peptide and to determine the hTERT specific cytotoxic T lymphocyte response elicited by DCs transfected with hTERT lentivirus vectors in vitro. LVs encoding the hTERT peptide were constructed, DCs from cord blood were prepared, their morphology was observed and phenotype was analyzed by flow cytometry. Lenti-hTERT was transfected into DCs to construct the DC vaccines. T lymphocytes stimulated with DC vaccines and HepG2 cells (hTERT+) or 293T cells (hTERT-) were co-cultured for 24 h, respectively. The ability to stimulate proliferation of allogeneic T lymphocytes and the killing activity of CTLs activated by these DCs were determined using the MTT method. According to our results, the recombinant vector lenti-hTERT and lenti-hTERT-DC vaccine were successfully constructed. The stimulatory capacity of the lenti-hTERT DCs in the allogeneic T lymphocyte reaction was markedly enhanced compared with the DC control group (P<0.01). Inhibition rates in HepG2 cells of CTLs stimulated with lenti-hTERT-DCs (CTLT) were significantly higher than CTLs stimulated with the control DC group (CTLN) (P<0.01). Inhibition rates in 293T cells of CTLT and CTLN were low and there was no difference between the different DC groups (P>0.05). DCs transfected with the hTERT peptide were capable of eliciting a stronger hTERT specific CTL response in vitro. Our data indicate that lenti-hTERT-DCs may potentially be used as an effective approach for cancer immunotherapy. PMID- 21971749 TI - Sampling-based exploration of folded state of a protein under kinematic and geometric constraints. AB - Flexibility is critical for a folded protein to bind to other molecules (ligands) and achieve its functions. The conformational selection theory suggests that a folded protein deforms continuously and its ligand selects the most favorable conformations to bind to. Therefore, one of the best options to study protein ligand binding is to sample conformations broadly distributed over the protein folded state. This article presents a new sampler, called kino-geometric sampler (KGS). This sampler encodes dominant energy terms implicitly by simple kinematic and geometric constraints. Two key technical contributions of KGS are (1) a robotics-inspired Jacobian-based method to simultaneously deform a large number of interdependent kinematic cycles without any significant break-up of the closure constraints, and (2) a diffusive strategy to generate conformation distributions that diffuse quickly throughout the protein folded state. Experiments on four very different test proteins demonstrate that KGS can efficiently compute distributions containing conformations close to target (e.g., functional) conformations. These targets are not given to KGS, hence are not used to bias the sampling process. In particular, for a lysine-binding protein, KGS was able to sample conformations in both the intermediate and functional states without the ligand, while previous work using molecular dynamics simulation had required the ligand to be taken into account in the potential function. Overall, KGS demonstrates that kino-geometric constraints characterize the folded subset of a protein conformation space and that this subset is small enough to be approximated by a relatively small distribution of conformations. PMID- 21971750 TI - An early botulinum toxin A treatment in subacute stroke patients may prevent a disabling finger flexor stiffness six months later: a randomized controlled trial. AB - OBJECTIVE: The study asked whether an early botulinum toxin A (BTX-A) injection in subacute stroke patients may prevent a disabling finger flexor stiffness six months later. DESIGN: Single-blind, randomized pilot study. SETTING: Inpatient rehabilitation centre. SUBJECTS: Eighteen stroke patients, interval 4-6 weeks, non-functional arm, Fugl-Meyer arm score (0-66) <20, beginning elevated finger flexor tone, randomly allocated to group A or B. INTERVENTIONS: In group A patients 150 units BTX-A (Xeomin) injected into the deep and superficial finger (100 units) and wrist flexors (50 units), no injection in group B patients. Comprehensive rehabilitation in both groups. MAIN MEASURES: Primary variable was the Modified Ashworth Scale score (0-5) of the finger flexors; secondary variables were whole arm muscle tone with REPAS (a summary rating scale for resistance to passive movement), its motor control with the Fugl-Meyer arm score, and a disability scale, blindly assessed at T0 (start), T1 (four weeks) and T6 (six months). RESULTS: Homogeneous groups at T0. Significantly less finger flexor stiffness in the BTX-A group at T1 and T6, the mean (SD) Modified Ashworth Scale scores in group A (B) were: 1.7 +/- 0.5 (1.6 +/- 0.5) at T0; 0.4 +/- 0.5 (1.9 +/- 0.7) at T1; and 1.4 +/- 0.7 (2.4 +/- 0.9) at T6. Among the secondary measures, the disability score, namely the items pain and passive nail trimming, was lower in group A at T1 and T6. CONCLUSIONS: The results indicate an effect of early BTX A injection on finger flexor stiffness six months later, presumably attributable to a reduced contracture development. Effect size calculation suggests inclusion of at least 17 patients per group excluding drop-outs in a warranted placebo controlled trial. PMID- 21971751 TI - Healthcare tariffs for specialist inpatient neurorehabilitation services: rationale and development of a UK casemix and costing methodology. AB - OBJECTIVE: To describe the rationale and development of a casemix model and costing methodology for tariff development for specialist neurorehabilitation services in the UK. RATIONALE FOR DEVELOPMENT OF A NEW METHODOLOGY: Patients with complex needs incur higher treatment costs. Fair payment should be weighted in proportion to costs of providing treatment, and should allow for variation over time CASEMIX MODEL AND BAND-WEIGHTING: Case complexity is measured by the Rehabilitation Complexity Scale (RCS). Cases are divided into five bands of complexity, based on the total RCS score. The principal determinant of costs in rehabilitation is staff time. Total staff hours/week (estimated from the Northwick Park Nursing and Therapy Dependency Scales) are analysed within each complexity band, through cross-sectional analysis of parallel ratings. A 'band weighting' factor is derived from the relative proportions of staff time within each of the five bands. COSTING METHODOLOGY: Total unit treatment costs are obtained from retrospective analysis of provider hospitals' budget and accounting statements. Mean bed-day costs (total unit cost/occupied bed days) are divided broadly into 'variable' and 'non-variable' components. In the weighted costing model, the band-weighting factor is applied to the variable portion of the bed day cost to derive a banded cost, and thence a set of cost-multipliers. Preliminary data from one unit are presented to illustrate how this weighted costing model will be applied to derive a multilevel banded payment model, based on serial complexity ratings, to allow for change over time. PMID- 21971752 TI - Efficacy of electromyographic biofeedback and electrical stimulation following arthroscopic partial meniscectomy: a randomized controlled trial. AB - OBJECTIVE: To compare the effectiveness of electromyographic biofeedback training and electrical stimulation therapy for rehabilitation following arthroscopic partial meniscectomy. DESIGN: Randomized, prospective, controlled single-blind trial. SETTING: Department of physical medicine and rehabilitation, university hospital. SUBJECTS: Forty-five patients who had undergone surgery for arthroscopic partial meniscectomy were randomly divided into three groups with 15 patients in each group. INTERVENTIONS: The control group had home exercise, the second and third groups received electromyographic biofeedback training or electrical stimulation therapy to quadriceps muscle in addition to home exercise. MAIN MEASURES: The patients were evaluated for: visual analogue scale, gait velocity (m/s), time using a walking aid after surgery, Lysholm Knee Scoring Scale score, knee flexion-extension angle, maximum and average contraction powers of vastus medialis obliquus and vastus lateralis muscles on the day before the operation and two and six weeks after. RESULTS: The time using a walking aid was 8.3 +/- 8.0, 1.5 +/- 2.5 and 4.5 +/- 5.5 days, respectively, for the home exercise, electromyographic biofeedback training and electrical stimulation groups, and significantly shorter in the electromyographic biofeedback training than in the home exercise group (P < 0.017). While significant progress was detected in Lysholm Knee Scoring Scale score in the second and sixth postoperative weeks compared to the preoperative within-group evaluation for each of the three groups (P < 0.017), there was significant difference in Lysholm Knee Scoring Scale in the second postoperative week in favour of electromyographic biofeedback training compared to home exercise (P < 0.017). There were significant differences in vastus medialis obliquus average and vastus lateralis maximum and average contractions in favour of electromyographic biofeedback compared to home exercise and electrical stimulation in the second postoperative week (P < 0.017). CONCLUSIONS: The addition of electromyographic biofeedback training to a conventional exercise programme following arthroscopic partial meniscectomy helps to speed up the rehabilitation process. PMID- 21971753 TI - Inpatient versus home-based rehabilitation for older adults with musculoskeletal disorders: a systematic review. AB - OBJECTIVE: To review and summarize available evidence to compare the outcomes of home-based rehabilitation to inpatient rehabilitation for older patients with musculoskeletal conditions. DATA SOURCES: Relevant articles published prior to August 2011 were identified using MEDLINE, CINAHL and the Cochrane Central Register of Controlled Trials databases. REVIEW METHODS: English-language articles that compared patient outcomes of home-based and inpatient rehabilitation for older adults were included. Outpatient care was not included as home-based or inpatient rehabilitation. Methodological quality of included studies was evaluated by two reviewers using the PEDro scale. RESULTS: A systematic search yielded eight randomized controlled trials and four cohort studies. Older adults who received rehabilitation in the home had equal or higher gains than the inpatient group in function, cognition, and quality of life; they also reported higher satisfaction. CONCLUSION: Home-based rehabilitation may be an effective alternative for treating older patients with musculoskeletal conditions. PMID- 21971754 TI - Effects of treadmill training with optic flow on balance and gait in individuals following stroke: randomized controlled trials. AB - OBJECTIVE: This study examined the effects of treadmill training with optic flow on the functional recovery of balance and gait in stroke patients. DESIGN: Randomized controlled experimental study. PARTICIPANTS: Thirty patients following stroke were divided randomly into the treadmill with optic flow group (n = 10), treadmill group (n = 10) and control group (n = 10). INTERVENTIONS: The subjects in the experimental group wore a head-mounted display to receive speed-modulated optic flow during treadmill training for 30 minutes, while those in the treadmill group and control group received treadmill training and regular therapy for the same time, three times a week for four weeks. MAIN MEASURES: The data were collected using timed up-and-go test, functional reach test, 10-m walk test, and six-minute walk test before and after treatment. RESULTS: The timed up-and-go test in the treadmill with optic flow group (5.55 +/- 2.04) improved significantly greater than the treadmill (1.50 +/- 0.93) and control (0.40 +/- 0.84) groups. The functional reach test in the treadmill with optic flow group (2.78 +/- 1.44) was significantly higher than the control group (0.20 +/- 0.16) only. The gait velocity in the treadmill with optic flow group (0.21 +/- 0.06) showed a significant decrease compared to the treadmill (0.03 +/- 0.02) and control (0.01 +/- 0.02) groups. Finally, the six-minute walk test in the treadmill with optic flow group (24.49 +/- 11.00) showed significant improvement compared to the treadmill training (4.65 +/- 3.25) and control (1.79 +/- 3.08) groups. CONCLUSION: Treadmill using optic flow speed modulation improves the balance and gait significantly in patients with stroke who are able to participate in physical gait training. PMID- 21971755 TI - A randomized controlled trial of electrostimulation effects on effussion, swelling and pain recovery after anterior cruciate ligament reconstruction: a pilot study. AB - OBJECTIVE: To evaluate rehabilitation results of electrostimulation especially on joint effusion, swelling and pain recovery after anterior cruciate ligament reconstruction. DESIGN: A randomized controlled trial; the assessor was not blinded to the group allocation. SETTING: Orthopaedics-traumatology and physical medicine-rehabilitation departments. SUBJECTS: Twenty-nine consecutive patients underwent anterior cruciate ligament reconstruction. INTERVENTIONS: Both groups began the voluntary exercise protocol one day post-surgery. The intervention group (n = 15) also received 30 sessions electrostimulation treatment protocol started four days after the operation. MAIN MEASURES: Numerical bulge-dancing patella signs for effusion assessment; differences in circumferences of the mid centre of the patella between operated and non-operated knees for swelling assessment. A self-report of average daily resting pain assessed by visual analogue scale; Intenational Knee Documentation Committee scoring system and Tegner Activity Scale for subjective response assessment. RESULTS: Twenty-six subjects including 13 patients from the intervention group completed the study. Significantly less effusion and swelling were determined in the intervention group after seven days (1.8 +/- 1.3 versus 2.4 +/- 1.7 for effusion and 1.7 +/- 1.2 versus 3.4 +/- 1.5 for swelling) to 12 weeks (0.2 +/- 0.7 versus 0.6 +/- 0.8 for effusion and 0.2 +/- 0.8 versus 0.8 +/- 0.9 for swelling) postoperative (P < 0.05). Patients treated with electrostimulation had significantly lower pain scores from seven days up to 12 weeks after the operation (P < 0.05). CONCLUSION: Electrostimulation along with exercise therapy appears superior to exercise alone regarding knee effusion, swelling and pain recovery after anterior cruciate ligament reconstruction. Still, there is need for further clinical studies using a radiologic method to demonstrate this effect of electrostimulation. PMID- 21971756 TI - Measures of sensation in neurological conditions: a systematic review. AB - OBJECTIVE: To systematically review the psychometric properties and clinical utility of measures of sensation in neurological conditions to inform future research studies and clinical practice. DATA SOURCES: Electronic databases (MEDLINE, CINAHL, EMBASE and AMED) were searched from their inception to December 2010. REVIEW METHODS: Search terms were used to identify articles that investigated any sensory measures in neurological conditions. Data about their psychometric properties and clinical utility were extracted and analyzed independently. The strength of the psychometric properties and clinical utility were assessed following recommendations. (1) RESULTS: Sixteen sensory measures were identified. Inter-rater reliability and redundancy of testing protocols are particular issues for this area of assessment. Eleven were rejected because they were not available for a researcher or clinician to use. Of the remaining five measures, the Erasmus MC modifications of the Nottingham Sensory Assessment and the Sensory section of the Fugl-Meyer Assessment showed the best balance of clinical utility and psychometric properties. CONCLUSION: Many measures of sensory impairment have been used in research but few have been fully developed to produce robust data and be easy to use. At present, the sensory section of the Fugl-Meyer Assessment and the Erasmus MC modifications of the Nottingham Sensory Assessment show the most effective balance of usability and robustness, when delivered according to the operating instructions. PMID- 21971757 TI - The dilemma of diagnostic uncertainty when treating people with chronic low back pain: a qualitative study. AB - OBJECTIVE: To investigate how physiotherapists prescribe execise for people with non-specific chronic low back pain in the absence of definitive or differential diagnoses. DESIGN: Four guided focus groups were conducted to gather the views of physiotherapists working in primary care. SUBJECTS AND SETTING: Twenty-three primary care physiotherapists from metropolitan Melbourne, Australia, were identified from professional organization member lists and publicly available records. They were recruited via email and assembled for focus groups based on eligibility, availability and location. MAIN MEASURES: Discussions were audio taped, transcribed verbatim and analysed for themes by three independent researchers. RESULTS: The 'dilemma created by diagnostic uncertainty' emerged as a significant overarching theme with the following subthemes. Physiotherapists: (1) perceive that care-seekers want a clear diagnosis, (2) are challenged by diagnostic uncertainty, (3) are critical when patients fail to improve, (4) feel unprepared by traditional education models and (5) seek support from experienced colleagues. Physiotherapists report needing to: (1) educate care-seekers about their injury/diagnosis, despite diagnostic uncertainty, and (2)observe rapid health outcome improvements. They exhibit potentially negative behaviours, including blame attribution, when this does not occur. CONCLUSIONS: Physiotherapists appear under-prepared for the challenges of working with people with chronic conditions. Quality research is warranted to determine best practice in supporting practitioners in the development of suitable therapeutic behaviours to deal with this challenging patient interface. PMID- 21971759 TI - Why is RCM favoured over dimerisation? Predicting and estimating thermodynamic effective molarities by solution experiments and electronic structure calculations. AB - The thermodynamic effective molarities of a series of simple cycloalkenes, synthesised from alpha,omega-dienes by reaction with Grubbs' second generation precatalyst, have been evaluated. Effective molarities were measured from a series of small scale metathesis reactions and agreed well with empirical predictions derived from the number of rotors and the product ring strain. The use of electronic structure calculations (at the M06-L/6-311G** level of theory) was explored for predicting thermodynamic effective molarities in ring-closing metathesis. However, it was found that it was necessary to apply a correction to DFT-derived free energies to account for the entropic effects of solvation. PMID- 21971758 TI - Increased oxidative damage and decreased antioxidant function in aging human substantia nigra compared to striatum: implications for Parkinson's disease. AB - Parkinson's disease (PD) is characterized by selective degeneration and loss of dopaminergic neurons in the substantia nigra (SN) of the ventral mid brain leading to dopamine depletion in the striatum. Oxidative stress and mitochondrial damage have been implicated in the death of SN neurons during the evolution of PD. In our previous study on human PD brains, we observed that compared to SN, striatum was significantly protected against oxidative damage and mitochondrial dysfunction. To understand whether brain aging contributes to the vulnerability of midbrain to neurodegeneration in PD compared to striatum, we assessed the status of oxidant and antioxidant markers, glutathione metabolic enzymes, glial fibrillary acidic protein (GFAP) expression and mitochondrial complex I(CI) activity in SN (n = 23) and caudate nucleus (n = 24) during physiological aging in human brains. We observed a significant increase in protein oxidation (P < 0.001), loss of CI activity (P = 0.04) and increased astrocytic proliferation indicated by GFAP expression (P < 0.001) in SN compared to CD with increasing age. These changes were attributed to significant decrease in antioxidant function represented by superoxide dismutase (SOD) (P = 0.03), glutathione (GSH) peroxidase (GPx) (P = 0.02) and GSH reductase (GR) (P = 0.03) and a decreasing trend in total GSH and catalase with increasing age. However, these parameters were relatively unaltered in CD. We propose that SN undergoes extensive oxidative damage, loss of antioxidant and mitochondrial function and increased GFAP expression during physiological aging which might make it more vulnerable to neurotoxic insults thus contributing to selective degeneration during evolution of PD. PMID- 21971760 TI - Toll-like receptors 2 and 3 agonists differentially affect oligodendrocyte survival, differentiation, and myelin membrane formation. AB - Toll-like receptors (TLRs) play a key role in controlling innate immune responses to a wide variety of pathogen-associated molecules as well as endogenous signals. In addition, TLR expression within nonimmune cells has been recognized as as modulator of cell behavior. In this study we have addressed the question of whether functional TLRs are expressed on oligodendrocytes, the myelinating cells of the central nervous system. Primary cultures of rat oligodendrocytes at different maturation stages were found to express TLR2 and, to lesser extent, TLR3. Immunocytochemical analysis revealed that both TLRs were localized at the cell body and primary processes and were excluded from myelin-like membranes. Interestingly, innate immune receptor ligands were able to modulate oligodendrocyte survival, differentiation, and myelin-like membrane formation, indicating that TLRs on oligodendrocytes are functional. In highly purified oligodendrocytes cultures, the TLR2 agonist zymosan promoted survival, differentiation, and myelin-like membrane formation, whereas poly-I:C, a TLR3 ligand, was a potent inducer of apoptosis. Together, these data indicate that, in addition to other neural cell types, also oligodendrocytes express functional TLRs, which play a role in regulating various aspects of oligodendrocyte behavior. PMID- 21971762 TI - Squamous epithelial changes of the larynx: diagnosis and therapy. AB - It can be confusing for clinicians to work their way through the tangle of pathologic terms used in surgical pathology reports to describe squamous abnormalities in laryngeal biopsies. After a brief review of the normal microscopic anatomy of the larynx and time-honored clinical designations for surface-based abnormalities, this report sorts pathologic changes into 2 groups: those changes that do not carry a premalignant potential (including squamous metaplasia, squamous hyperplasia, pseudoepitheliomatous hyperplasia, keratosis, and parakeratosis) and those that do (including dyskeratosis, laryngeal intraepithelial neoplasia [LIN], atypia, dysplasia, and carcinoma in situ). Generally, lesions in the first group do not require additional therapy or close follow-up; lesions in the second group, however, demand either some form of local therapy or close follow-up to monitor for the development of a more aggressive pathology. PMID- 21971761 TI - What is the blood pressure goal for the elder patient 75 years of age or older? AB - High blood pressure (BP), once believed to represent a normal and progressive component of the aging process, is now recognized as a manifestation of structural and physiologic abnormalities of arterial function. Two phenotypes exist in the older patient: elevated systolic blood pressure (SBP) and diastolic blood pressure (DBP) with a normal pulse pressure (PP), and elevated SBP with an increased PP. Elevated SBP and increased PP unquestionably increase the risk of both fatal and nonfatal cardiovascular events, including stroke, myocardial infarction, and heart failure. Isolated systolic hypertension, defined as an SBP >=140 mm Hg with a DBP less than 90 mm Hg, affects the majority of individuals ages 60 years and older. A number of clinical trials have clearly demonstrated that treatment of hypertension significantly reduces the cardiovascular event rate in older patients. However, controversy continues as to the choice of antihypertensive agents and combinations of agents. It is both appropriate and necessary to treat elderly hypertensive patients aggressively to the same target BPs identified for younger patients. It is also appropriate to initiate treatment with lower doses of antihypertensive agents and to bring the pressure down more slowly, monitoring for orthostatic hypotension, impaired cognition, and electrolyte abnormalities. PMID- 21971763 TI - Transformations of aryl isothiocyanates on tetraphosphine tungsten complexes and reactivity of the resulting dithiocarbonimidate ligand. AB - Treatment of [WH(4)(kappa(4)-P4)] (3: P4 = meso-o C(6)H(4)(PPhCH(2)CH(2)PPh(2))(2)) with aryl isothiocyanate ArNCS at 50 degrees C afforded the dithiocarbonimidate-isocyanide complex [W(kappa(2) S(2)CNAr)(CNAr)(kappa(4)-P4)] (4) in moderate yields. The reaction also produced ArNHCH(3) and a small amount of ArNH(2). The yield of the hydrodesulfurization product ArNHCH(3) increased when the reaction was conducted under H(2) (up to 0.65 equiv. to 3 for Ar = p-MeC(6)H(4) (Tol)). Complex 4 was proposed to be formed via reductive disproportionation of two ArNCS molecules on a zero-valent W species generated by dissociation of H(2) from 3. The reaction of W(0) complex [W(dppe)(kappa(4)-P4)] (dppe = Ph(2)PCH(2)CH(2)PPh(2)) with ArNCS also yielded 4 accompanied by free dppe, in contrast to that of [Mo(dppe)(kappa(4)-P4)], which had been previously reported to undergo sulfur-atom transfer to phosphine ligands. The dithiocarbonimidate ligands in 4a (Ar = Tol) received the addition of electrophiles [PhMe(2)NH][BF(4)], MeI, and PhCOCl selectively at the N atom to afford the cationic dithiocarbamate complexes [W(kappa(2) S(2)CNHTol)(CNTol)(kappa(4)-P4)][BF(4)] (6), [W{kappa(2) S(2)CN(Me)Tol}(CNTol)(kappa(4)-P4)]I (7), and [W{kappa(2) S(2)CN(COPh)Tol}(CNTol)(kappa(4)-P4)]Cl (8). Complexes 4a, 6, 7, and 8 have been characterized by spectroscopic and crystallographic methods, and the donor strengths of their kappa(2)-dithio ligands are discussed. PMID- 21971764 TI - Tunable compositions and luminescent performances on members of the layered rare earth hydroxides (Y1-xLnx)2(OH)5NO3.nH2O (Ln = Tb, Eu). AB - Members of the layered rare-earth hydroxides (LRHs) family with the generalized formula (Y(1-x)Ln(x))(2)(OH)(5)NO(3).nH(2)O (Ln = Tb, Eu; 0% <=x<= 100%) (named as YTb-LRHs, YEu-LRHs) have been synthesized via a hydrothermal route. Crystal structures and elemental compositions have been investigated by X-ray diffraction (XRD), elemental analysis, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). These results show that Ln(3+) species are successfully incorporated into the LRH host lattice to form layered hydroxide solid solutions. The YTb-LRHs and YEu-LRHs samples exhibit well-defined photoluminescence. The color of the luminescence can be tuned by changing the concentration of Ln(3+). Furthermore, the ternary YTbEu-LRH system was also synthesized, an example of the host layers containing variable types of the lanthanide cations. This provides the possibility to tune the chemical composition and the luminescent properties of the lanthanide species with the flexibility of intercalation hosts for potential applications in luminescent materials and field emission displays. PMID- 21971765 TI - Metronomic therapy concepts in the management of adrenocortical carcinoma. AB - Metronomic chemotherapy is the administration of cytotoxic drugs at low doses, on a frequent or continuous schedule, with no extended interruption. This treatment approach can target tumor cells indirectly since it can affect the endothelium of the growing tumor vasculature and stimulates the anticancer immune response. Both the antiangiogenetic and the immunomodulatory roles of metronomic chemotherapy favor a tumor dormancy, a condition that may improve the patient outcome. Prospective clinical trials conducted in several malignancies have shown that metronomic chemotherapy can obtain disease stabilization or responses in tumors that had been made resistant in vivo to conventional chemotherapeutic regimens. Three prospective phase II trials have been conducted in patients with adrenocortical carcinoma (ACC). In all of them, patients heavily pretreated with conventional chemotherapy and mitotane have been enrolled. One trial tested the activity of the association of gemcitabine and fluoropyrimidines administered on a metronomic schedule. In this trial, 40% of patients attained a disease stabilization or disease response that was long lasting in some of them. In the remaining two trials, metronomic chemotherapy was administered in association with antiangiogenetic drugs, and the results were disappointing since no response or stable disease was obtained. In conclusion, metronomic chemotherapy can delay tumor progression in advanced ACC and deserves to be further tested. The concomitant administration of antiangiogenetic drugs may be detrimental. Several important questions remain to be addressed such as the optimal dose and most effective dosing interval, when to use the metronomic approach in the natural history of the disease, the choice of cytotoxic drugs, and the most efficacious way to integrate metronomic chemotherapy with standard therapy protocols. PMID- 21971766 TI - Measuring the potency labelling of onabotulinumtoxinA (Botox((r))) and incobotulinumtoxinA (Xeomin ((r))) in an LD50 assay. AB - The biological potency of botulinum toxin (BT) drugs is determined by a standardised LD50 assay. However, the potency labelling varies vary amongst different BT drugs. One reason for this may be differences in the LD50 assays applied. When five unexpired batches of onabotulinumtoxinA (Botox((r))) and incobotulinumtoxinA (Xeomin((r))) are compared in the Xeomin((r)) batch release assay, the potency variability of both BT drugs fell within the range allowed by the European Pharmacopoiea. Statistical analyses failed to detect differences in the potency labelling of both products. Although the existence of a conversion ratio has been questioned recently, our experimental data are in line with previous clinical experience showing that Botox((r)) and Xeomin((r)) can be compared using a 1:1 conversion ratio. Identical potency labelling allows easy exchange of both BT drugs in a therapeutic setting, and direct comparison of efficacy, adverse effects and costs. PMID- 21971767 TI - Radiation induces epithelial-mesenchymal transition in colorectal cancer cells. AB - Radiotherapy remains a major approach to adjuvant therapy for patients with advanced rectal cancer. Nevertheless, the effects of radiation on malignant processes have yet to be clarified. The aim of this study was to assess the biological effects of radiation on colorectal cancer (CRC) cells with special reference to epithelial-mesenchymal transition (EMT), a key developmental program often activated during cancer invasion and metastasis. We investigated the effect of radiation on two colorectal cancer cell lines, CaR1 and DLD1, assessing cell morphology, motility, migration and invasive ability. Expression of molecules associated with EMT was determined using RT-PCR, Western blotting, and immunofluorescence staining in control and irradiated cells. We also used real time RT-PCR to examine the expression of molecules associated with EMT before and after chemoradiotherapy. Thus, we studied 26 rectal cancer patients who received preoperative chemoradiotherapy followed by radical surgery. In addition, we examined the relationship between disease recurrence and the expression of a number of proteins. Irradiation caused CRC cells to undergo phenotypic changes characteristic of EMT: spindle-cell shape, loss of polarity, intercellular separation and pseudopodia formation. Irradiation enhanced cell migration and invasiveness. In irradiated CRC cells, molecular changes consistent with EMT were observed. In clinical samples, we observed molecular changes consistent with EMT, and those changes were significantly enhanced in patients with recurring disease. These results indicate that irradiation induces an alteration to a malignant phenotype consistent with EMT in colorectal cancer cells. PMID- 21971768 TI - [Galli-Galli disease. Clinical and histopathological investigation using a case series of 18 patients]. AB - Galli-Galli disease, a rare genodermatosis belonging to the spectrum of reticulate pigment dermatoses, is classified as an acantholytic variant of Dowling-Degos disease on the basis of its characteristic clinical and histological findings. In the context of this case series, Galli-Galli disease is characterized in detail based on the clinical and histopathological evaluation of 18 patients. The disease pattern is discussed in view of the current literature. In addition, a classification into two clinical subtypes is made and a genotype/phenotype correlation with mutations in the keratin 5 (KRT5) gene is established. PMID- 21971769 TI - [Maculo-papular exanthem with acute renal failure. Drug-induced hypersensitivity syndrome]. AB - Acute renal failure caused by interstitial nephritis as part of a drug hypersensitivity syndrome constitutes a rare, but potentially life-threatening adverse drug reaction. We describe a patient with a mild maculo-papular rash accompanied by eosinophilia after prolonged treatment with meropenem, vancomycin, and moxifloxacin. Subsequently, a rapidly progressing renal failure developed which dominated the clinical picture. Upon cessation of all suspected drugs and therapy with high-dose steroids for 6 weeks, the renal function slowly returned to normal. PMID- 21971770 TI - [Frontal fibrosing alopecia with androgenetic pattern. A diagnostic challenge - a therapeutic problem]. AB - Diagnosis of scarring alopecia is a particular diagnostic and therapeutic challenge. Frontal fibrosing alopecia was first described by Kossard as a scarring alopecia characterized by progressive recession of the frontal-temporal hair margins leading to permanent alopecia. Primarily affected are postmenopausal women. A 56 year-old woman presented with fibrosing alopecia in a male-pattern distribution. Evaluation of medical history, clinical, dermoscopic and histopathological findings led us to the diagnosis of frontal fibrosing alopecia with additional androgenetic pattern. Other forms of scarring alopecia have to be considered as differential diagnoses. This case emphasizes that dermoscopy of the scalp should become an integral part of the diagnosis of scalp diseases. PMID- 21971772 TI - Marcos Mercadante (1960-2011) and his legacy to Brazilian psychiatry. PMID- 21971773 TI - Targeting the NMDA receptor-nitric oxide-cyclic GMP pathway to develop non dopaminergic antipsychotic medications for schizophrenia. PMID- 21971774 TI - Brief motivational interview and educational brochure in emergency room settings for adolescents and young adults with alcohol-related problems: a randomized single-blind clinical trial. AB - OBJECTIVE: To evaluate the effectiveness of brief motivational interviewing and an educational brochure when delivered in emergency room to reduce alcohol abuse and related problems among adolescents and young adults. METHOD: A randomized single-blind clinical trial with a three-month follow-up was carried out at three emergency rooms from October 2004 to November 2005; subjects assessed were 16-25 years old treated for alcohol related events up to 6 hours after consumption. Socio-demographic data, quantity, frequency and negative consequences of alcohol consumption, motivation to change habits and future risk perception were evaluated. Statistical analysis was performed on subjects who completed follow-up (completers). ANCOVA model was used to analyze the difference between the intervention groups with statistical significance level alpha = 5% and confidence interval (CI) of 95%. RESULTS: 186 subjects formed the initial sample, being 175 included and randomized to the educational brochure group (n = 88) or motivational interviewing group (n = 87). Follow-up assessment was performed in 85.2% of the sample. No significant difference between groups was observed. However, significant reductions (p < 0.01) in related problems and alcohol abuse were found in both groups. CONCLUSION: In this sample a reduction of alcohol use and related problems was observed. Preliminary data indicate that controlled clinical trials with motivational interviewing, educational brochure and nonintervention should be of future interest among Brazilian adolescent populations. PMID- 21971775 TI - Applicability of the Rey auditory-verbal learning test to an adult sample in Brazil. AB - OBJECTIVE: The Rey Auditory-Verbal Learning Test, which is used to evaluate learning and memory, is a widely recognized tool in the general literature on neuropsychology. This paper aims at presenting the performance of Brazilian adult subjects on the Rey Auditory-Verbal Learning Test, and was written after we published a previous study on the performance of Brazilian elderly subjects on this same test. METHOD: A version of the test, featuring a list of high-frequency one-syllable and two-syllable concrete Portuguese substantives, was developed. Two hundred and forty-three (243) subjects from both genders were allocated to 6 different age groups (20-24; 25-29; 30-34; 35-44; 45-54 and 55-60 years old). They were then tested using the Rey Auditory-Verbal Learning Test. RESULTS: Performance on the Rey Auditory-Verbal Learning Test showed a positive correlation with educational level and a negative correlation with age. Women performed significantly better than men. When applied across similar age ranges, our results were similar to those recorded for the English version of the Rey Auditory-Verbal Learning Test. CONCLUSION: Our results suggest that the adaptation of the Rey Auditory-Verbal Learning Test to Brazilian Portuguese is appropriate and that it is applicable to Brazilian subjects for memory capacity evaluation purposes and across similar age groups and educational levels. PMID- 21971776 TI - The relationship between perceived social support and severity of body dysmorphic disorder symptoms: the role of gender. AB - OBJECTIVE: Whether social support is associated with severity of body dysmorphic symptoms is unknown. To address this gap in the literature, the present study aims to examine the association between three domains of perceived social support (i.e., family, friends, and significant others) and severity of body dysmorphic disorder symptoms. METHOD: Participants (N = 400) with symptoms consistent with diagnosis of body dysmorphic disorder completed measures of symptomatology and social support via the internet. RESULTS: More perceived social support from friends and significant others was associated with less severe body dysmorphic disorder symptoms for males, and more perceived social support from family and friends was associated with less severe body dysmorphic disorder symptoms among females. Additionally, gender moderated the association between perceived social support from significant others and symptom severity, such that perceived social support from a significant other was significantly negatively associated with body dysmorphic symptom severity in males, but not females. CONCLUSION: The present study implicates social support as an important area of future body dysmorphic disorder research. PMID- 21971777 TI - Quality of life, diagnosis, and treatment of patients with major depression: a prospective cohort study in primary care. AB - OBJECTIVE: To describe the demographic and clinical characteristics, adequacy of antidepressant treatment, and changes in quality of life of patients with major depression receiving follow-up care from primary care centers. METHOD: A cohort study was performed in which major depression patients were followed-up over a nine-month period. Several evaluation instruments were used, including the World Health Organization Quality of Life and the Quality of Life-Depression, Centers for Epidemiologic Studies-Depression questionnaires. RESULTS: The sample comprised 179 individuals, mostly female (73%), with a mean age of 38 years and mean education of 9 years. At the end of the follow-up period, 42% of the individuals still presented with major depression, 25% had complete symptom remission, and only 9% were properly treated with antidepressants. In relation to quality of life, there were significant differences especially between baseline and after nine months in almost all measures. CONCLUSION: This study demonstrated that depressive symptoms are poorly recognized and that treatment is often inadequate for patients followed-up in primary care units in the south of Brazil. Most of the patients continued to have symptoms of depression over the nine-month period which were associated with impaired quality of life. PMID- 21971778 TI - Affective state dependence and relative trait stability of perfectionism in sleep disturbances. AB - OBJECTIVE: To evaluate the degree of absolute change, relative stability and state dependence of trait perfectionism in sleep disturbances in a sample of university students. METHOD: Participants completed the Multidimensional Perfectionism Scale and two items concerning sleep difficulties. The mean age at T0 (baseline) was 19.59 years (SD = 1.61, range = 17-25) and 62.5% of the sample were female. RESULTS: Absolute changes in self-oriented and socially-prescribed perfectionism were found. Relative stability was found for all perfectionism dimensions. Prior and concurrent sleep disturbances explained a significant amount of variance in perfectionism. Controlling for the effects of sleep measures, prior self-oriented perfectionism and other-oriented perfectionism were the only significant predictors of subsequent self-oriented perfectionism and other-oriented perfectionism, at T1 and T2. Difficulties falling asleep at T1 and socially-prescribed perfectionism at T0 were significant predictors of socially prescribed perfectionism at T1. CONCLUSION: Despite significant changes in perfectionism mean scores over the follow-up, the correlation analyses demonstrated that participants remained quite stable in regard to their relative levels of perfectionism. As concurrent difficulties initiating sleep also predicted concurrent socially-prescribed perfectionism, this seems to be one dimension of perfectionism with trait-state characteristics. PMID- 21971779 TI - Facial emotion recognition deficits in relatives of children with autism are not associated with 5HTTLPR. AB - OBJECTIVE: A large body of evidence suggests that several aspects of face processing are impaired in autism and that this impairment might be hereditary. This study was aimed at assessing facial emotion recognition in parents of children with autism and its associations with a functional polymorphism of the serotonin transporter (5HTTLPR). METHOD: We evaluated 40 parents of children with autism and 41 healthy controls. All participants were administered the Penn Emotion Recognition Test (ER40) and were genotyped for 5HTTLPR. RESULTS: Our study showed that parents of children with autism performed worse in the facial emotion recognition test than controls. Analyses of error patterns showed that parents of children with autism over-attributed neutral to emotional faces. We found evidence that 5HTTLPR polymorphism did not influence the performance in the Penn Emotion Recognition Test, but that it may determine different error patterns. CONCLUSION: Facial emotion recognition deficits are more common in first-degree relatives of autistic patients than in the general population, suggesting that facial emotion recognition is a candidate endophenotype for autism. PMID- 21971780 TI - Serum levels of IL-6, IL-10 and TNF-alpha in patients with bipolar disorder and schizophrenia: differences in pro- and anti-inflammatory balance. AB - OBJECTIVE: Previous reports suggest that cytokines act as potential mediators of the interaction between the immune and neuroendocrine systems, and that a proinflammatory state may be associated with bipolar disorder and schizophrenia. The aim is to compare cytokine levels in both disorders. METHOD: Twenty euthymic bipolar disorder patients, 53 chronic stabilized schizophrenia patients and 80 healthy controls were recruited. Subjects were all non-smokers and non-obese. Cytokines TNF-alpha, IL-6, and IL-10 were examined by sandwich ELISA. RESULTS: IL 6 levels were increased in schizophrenia patients when compared to controls (p < 0.0001) and euthymic bipolar disorder patients (p < 0.0001). IL-6 levels were no different in controls compared to euthymic bipolar disorder patients (p = 0.357). IL-10 was lower in controls compared to schizophrenia patients (p = 0.001) or to bipolar disorder patients (p = 0.004). There was no significant difference in TNF alpha serum levels among the groups (p = 0.284). Gender-based classification did not significantly alter these findings, and no correlation was found between the antipsychotic dose administered and cytokine levels in patients with schizophrenia. DISCUSSION: These findings evidence a chronic immune activation in schizophrenia. Bipolar disorder seems to present an episode-related inflammatory syndrome. Increased anti-inflammatory factor IL-10 in bipolar disorder and schizophrenia suggests different patterns of inflammatory balance between these two disorders. Results further support the need to investigate cytokines as possible biomarkers of disease activity or treatment response. PMID- 21971781 TI - Exposure to violence in incarcerated youth from the city of Sao Paulo. AB - OBJECTIVE: This study aimed to determine the extent of exposure to community violence among delinquent Brazilian youth in the 12-month period prior to their incarceration and to identify factors associated with this exposure. METHOD: With an oversampling of girls, a cross-section of youth under 18 years of age from juvenile detention units in the city of Sao Paulo, Brazil completed a structured interview. Key items related to exposure to violence (witnessed and experienced) were drawn from the Social and Health Assessment questionnaire to cover the 12 month period prior to incarceration. RESULTS: Participants (n = 325, 89% boys) reported high rates of exposure to violence with largely similar levels for boys and girls. Being threatened with physical harm, being beaten or mugged and/or shot at were the most common forms of violence experienced. After controlling for demographic and family variables, the fact of having peers involved in risk behavior, easy access to guns and previous involvement with the justice system were associated with witnessed violence; whereas having slept on the street was the only variable associated with experienced violence. CONCLUSION: This group of youth was exposed to high levels of violence and other adverse experiences. Future research should examine the effectiveness of strategies aimed at reducing the exposure to violence of high-risk youth. PMID- 21971782 TI - Paternal postpartum mood: bipolar episodes? AB - OBJECTIVE: We describe the prevalence of depressive and bipolar spectrum episodes in fathers in antenatal and postnatal periods, as well as at 12 months after childbirth. METHOD: A longitudinal follow-up study was conducted with a representative sample of 739 fathers whose children were born between April 2007 and May 2008 in maternity wards in the city of Pelotas, southern Brazil. Paternal psychopathology was measured with the Mini Neuropsychiatric Interview (MINI) across three time points: between 28 and 34 weeks of pregnancy (T1), 30 to 60 days postpartum (T2), and 12 months after childbirth (T3). RESULTS: The prevalence of depressive episodes was 5.0% at T1, 4.5% at T2, and 4.3% at T3. Mixed episodes were present in 3%, 1.7%, and 0.9% of subjects, respectively, and accounted for 61.1% of the cases of depression in the antenatal period, 37.5% in postpartum, and 21.4% at 12 months. Depressive and manic/hypomanic episodes were significantly associated during pregnancy and in postpartum, but not at 12 months after childbirth. CONCLUSION: Bipolar episodes were common in men with depressive symptoms during their partner's pregnancy in the postpartum period and, to a lesser extent, 12 months after childbirth. Therefore, this population should be carefully investigated for manic and hypomanic symptoms. PMID- 21971783 TI - Instruction in developmental psychiatry: preliminary findings at the undergraduate level in Brazil. AB - BACKGROUND: Although knowledge on developmental psychiatry is fundamental for the early recognition, treatment, and prevention of mental disorders, this subject has not been incorporated into the medical curriculum or psychiatric practice in Brazil. OBJECTIVE: To evaluate the effect of a short course on developmental psychiatry for undergraduate students and to expand education policies concerning developmental psychiatry in Brazil. METHODS: Before and after attending an extracurricular 12-hour, 4-day course on the fundamentals of developmental psychiatry, undergraduate health sciences students were tested regarding their knowledge of the subject. The pre-test/post-test included 12 randomly selected multiple-choice questions designed to evaluate knowledge related to developmental psychiatry and was administered together with a questionnaire designed to evaluate students' attitudes. To compare performances between groups, nonparametric analyses of ordinal categorical data were employed. RESULTS: The final sample comprised 43 students. The mean post-test score was significantly higher than the mean pre-test score (65.0% vs 39.9%; p < 0.0001). We found that strongly positive attitudes correlated with better performance. The 3rd and 4th year medical students performed better than the 1st and 2nd year medical students and the non-medical students. Sex differences favoring males were also observed. CONCLUSION: Our findings encourage additional educational policies related to developmental psychiatry which may result in direct clinical implications. PMID- 21971784 TI - [Guidelines of the Brazilian Medical Association for the treatment of social anxiety disorder]. AB - INTRODUCTION: Social anxiety disorder (SAD) is the most common anxiety disorder, usually with no remission, and is commonly associated with significant functional and psychosocial impairment. The Brazilian Medical Association (BMA), with the project named Diretrizes (Guidelines, in English), seeks to develop consensus for the diagnosis and treatment of common diseases. The aim of this article is to present the most important findings of the guidelines on the treatment of SAD, serving as a reference for the general practitioner and specialist. METHOD: The method used was proposed by the BMA. The search was conducted in the databases of MEDLINE (PubMed), Scopus, Web of Science and LILACS, between 1980 and 2010. The strategy used was based on structured questions as PICO (acronym formed by the initials of "patient or population", "intervention, display or exhibition", "control or comparison" and "outcome"). RESULTS: Studies show that the first-line pharmacological treatment for adults and children are serotonin selective reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors, whereas cognitive-behavioral therapy is considered the best psychotherapeutic treatment. Moreover, some psychiatric comorbidities were associated with a worse outcome of SAD. CONCLUSIONS: Despite its high prevalence, SAD does not receive adequate attention and treatment. The best choice for the treatment of adults is a combination of cognitive-behavioral psychotherapy with serotonin selective reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors. Other options as benzodiazepines or monoamine oxidase inhibitors must be used as second and third choices, respectively. PMID- 21971785 TI - [The safe sexual-affective relationship group for individuals with severe mental disorders]. PMID- 21971786 TI - Depression in general hospital inpatients: challenges for consultation-liaison psychiatry. PMID- 21971787 TI - Gastric neoplasia misdiagnosed as an eating disorder. PMID- 21971788 TI - Executive functions of interns after a night on call. PMID- 21971789 TI - Psychotic symptoms in social anxiety disorder with bipolar-like progression. PMID- 21971792 TI - Protein analysis by SDS-PAGE and detection by Coomassie blue or silver staining. PMID- 21971793 TI - Models of inflammation: measuring gastrointestinal ulceration in the rat. PMID- 21971794 TI - Overview of phosphoinositide hydrolysis. PMID- 21971795 TI - Nitric oxide synthase assays. PMID- 21971796 TI - Analysis of early gene responses. PMID- 21971797 TI - Cyclooxygenase assays. PMID- 21971798 TI - HIV protease assays. PMID- 21971799 TI - Topoisomerase assays. PMID- 21971800 TI - Protein farnesyltransferase assays. PMID- 21971801 TI - Overview of length-tension relationships in isolated tissue. PMID- 21971802 TI - Isolated cardiac muscle assays. PMID- 21971803 TI - Isolated blood vessel assays. PMID- 21971804 TI - alpha-Adrenoceptor assays. PMID- 21971805 TI - beta-Adrenoceptor assays. PMID- 21971806 TI - Opioid receptor assays. PMID- 21971807 TI - Angiotensin II receptor assays. PMID- 21971808 TI - Models of pulmonary disease: acute and chronic allergic asthma in the monkey and acute and chronic viral pulmonitis in the mouse. PMID- 21971809 TI - Models of pain: hot-plate and formalin test in rodents. PMID- 21971810 TI - Overview of receptor cloning. PMID- 21971811 TI - Receptor reporter systems. PMID- 21971812 TI - Expression of cloned receptors in mammalian cell lines. PMID- 21971813 TI - In vitro autoradiography. PMID- 21971814 TI - Overview of chemical diversity. PMID- 21971815 TI - The influence of physicians on colorectal cancer screening behavior. AB - BACKGROUND: Our aims were to determine clinical factors associated with colorectal cancer (CRC) screening and to evaluate the relative role of patient contact with physicians and the quality of these patient-physician interactions in affecting screening. METHODS: Screening-eligible patients were identified from the Health Information National Trends Survey. Determinants of CRC screening were assessed with logistic regression, and a joint effects model that considered the frequency and quality of contact with physicians was developed to explore their influence on screening. RESULTS: There were 4,615 respondents of whom only 66% reported receiving CRC screening. Older age, personal history of non-CRC, family history of any cancer, high-income earners, individuals who visited their physicians >=5 times per year, and those who rated the interactions with their physicians highly were more likely to be screened (all p < 0.05). The joint effects model revealed that quality rather than frequency of physician contact was a stronger predictor of CRC screening, but the odds of screening was highest for those who experienced both frequent and high-quality interactions with their physicians. CONCLUSIONS: Contact with physicians and the quality of this interaction are associated with screening behavior. Interventions to improve these provider-related factors may promote CRC screening. PMID- 21971816 TI - Patterns of meat intake and risk of prostate cancer among African-Americans in a large prospective study. AB - OBJECTIVE: Given the large racial differences in prostate cancer risk, further investigation of diet and prostate cancer is warranted among high-risk groups. The purpose of this study was to examine the association between type of meat intake and prostate cancer risk among African-American men. METHODS: In the large, prospective NIH-AARP Diet and Health Study, we analyzed baseline (1995 1996) data from African-American participants, aged 50-71 years. Incident prostate cancer cases (n = 1,089) were identified through 2006. Dietary and risk factor data were ascertained by questionnaires administered at baseline. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) within intake quantiles. RESULTS: Neither white nor processed meat intake was associated with prostate cancer, regardless of meat-cooking method. Red meats cooked at high temperatures were associated with an increased risk of prostate cancer (HR = 1.18, 95% CI = 1.00-1.38 and HR = 1.22, 95% CI = 1.03-1.44, for the upper two intake tertiles). Intake of the heterocyclic amine (HCA), 2-amino-3,4,8 trimethylimidazo[4,5-f] quinoxaline (DiMeIQx) was positively associated with prostate cancer (HR = 1.30; 95% CI = 1.05-1.61, p = 0.02). No associations were observed for intake of other HCAs. CONCLUSION: Red meats cooked at high temperatures were positively associated with prostate cancer risk among African American men. Further studies are needed to replicate these findings. PMID- 21971817 TI - Socioeconomic deprivation impact on meat intake and mortality: NIH-AARP Diet and Health Study. AB - OBJECTIVE: Previous studies have not examined potential interactions between meat intake and characteristics of the local environment on the risk of mortality. This study examined the impact of area socioeconomic deprivation on the association between meat intake and all-cause and cause-specific mortality after accounting for individual-level risk factors. METHODS: In the prospective NIH AARP Diet and Health Study, we analyzed data from adults, ages 50-71 years at baseline (1995-1996). Individual-level dietary intake and health risk information were linked to the demographic and socioeconomic context of participants' local environment based on census tract data. Deaths (n = 33,831) were identified through December 2005. Multilevel Cox models were used to estimate hazard ratios and 95% confidence intervals for quintiles of area deprivation scores. RESULTS: Associations of red and processed meats with mortality were consistent across deprivation quintiles. Men residing in least-deprived neighborhoods had a stronger protective effect for white meat consumption. No differences by deprivation index were observed for women. CONCLUSION: Red and processed meat intake increases mortality risk regardless of level of deprivation within a given neighborhood suggesting biological mechanisms rather than neighborhood contextual factors may underlie these meat-mortality associations. The effect of white meat intake on cancer mortality was modified by area deprivation among men. PMID- 21971818 TI - Do mosquito-associated bacteria of the genus Asaia circulate in humans? AB - Symbiotic bacteria of the genus Asaia have been proposed as tools for control of mosquito-borne diseases, specifically malaria. However, safety issues are a major concern for paratransgenesis strategies. The aim of this study is to investigate, with immunofluorescence assays and quantitative PCR experiments, whether Asaia spp. is circulating among humans. All human sera and whole blood samples analyzed were negative for Asaia spp., thus suggesting that this organism could be utilized, in the future, as a malaria control tool. PMID- 21971819 TI - Elevated soluble urokinase receptor values in CSF, age and bacterial meningitis infection are independent and additive risk factors of fatal outcome. AB - The aim of the present study was to evaluate the potential role of cerebrospinal fluid soluble urokinase receptor (suPAR) level, infection and age as risk factors for fatal outcome in patients suspected of having meningitis and/or bacteraemia on admission to hospital. A total of 545 cerebrospinal fluid samples from patients with clinically suspected meningitis were sent to the Hellenic National Meningitis Reference Laboratory. Ten of 545 (1.83%) patients died. Analysis by receiver operating characteristics (ROC) curve revealed that both suPAR and age were significant for prediction of fatal outcome. Patients with levels of suPAR above the cut-off values and age >= 51 years, or patients in which either Neisseria meningitis or Streptococcus pneumoniae were detected were categorized as high risk patients. The combination of the above three predictors (suPAR, age and infectious agent) in a logistic regression model with outcome of infection as the dependent variable yielded an overall odds ratio (OR = 85.7, 95% CI 10.6 690.2) with both sensitivity and specificity being equal to the value of 0.9. In conclusion, suPAR, age and type of infection have an additive effect in predicting mortality among patients suspected of meningitis. PMID- 21971820 TI - An observational efficacy and safety analysis of the treatment of acute invasive aspergillosis using voriconazole. AB - The purpose of this study was to evaluate efficacy and safety of voriconazole in patients with acute invasive aspergillosis (IA) in a real-life, clinical setting. This was a multicenter observational study in adult patients treated with voriconazole for invasive mycosis. The study evaluated clinical response, mortality, use of other licensed antifungal therapy (OLAT), and treatment duration. This sub-analysis evaluated treatment and outcome data specifically from adult patients with proven/probable IA, while safety data were assessed in patients with proven/probable/possible IA. Of the 141 patients enrolled, 113 were adults with proven/probable IA and six had possible IA. Voriconazole treatment duration ranged from 1 to 183 days (median, 49.5 days). Voriconazole was used exclusively in 64% (72/113) of patients and in combination/sequentially with OLAT in 36%. Overall successful treatment response was 50% (57/113 patients). Twelve percent (14/113) of patients were switched to OLAT, either because of insufficient response (four patients) or for safety reasons (10 patients). Overall and attributable (entirely or partially due to fungal infection) mortality rates were 52% (59/113) and 17%, respectively. Treatment-related adverse events were reported for 18% (22/119) of patients. This observational study confirms the results of previous clinical trials demonstrating voriconazole as an effective and safe agent for treatment of confirmed acute IA. PMID- 21971821 TI - Efficacy of chronic hepatitis C therapy with pegylated interferon and ribavirin in patients on methadone maintenance treatment. AB - A considerable number of patients undergoing methadone maintenance treatment (MMT) are not considered for treatment against hepatitis C virus (HCV) infection due to a possible lower adherence and efficacy in this population. We aimed to compare the response rates to HCV treatment in patients with or without MMT. HCV infected patients who initiated pegylated interferon plus ribavirin were included in this prospective cohort study. The relation between sustained virologic response (SVR) and MMT was analyzed. A total of 214 patients were included in the study [81 (37.9%) with and 133 (62.1%) without MMT]. No differences in HCV and interleukin 28B (rs12979860) genotype distribution were observed between the two groups. Of these patients, 103 (48.1%) achieved SVR. Among the patients who received MMT, 39 (48.1%) reached SVR compared to 64 (48.1%) subjects without MMT (p = 0.99). The frequency of voluntary drop-out and treatment discontinuations due to adverse events was comparable between the patients with and without MMT [10 (12.3%) versus 14 (10.5%), p = 0.68, and 4 (4.9%) versus 9 (6.8%), p = 0.59, respectively]. The efficacy of HCV therapy in MMT patients is similar to that found in subjects not taking methadone. MMT patients should be equally considered for treatment with pegylated interferon plus ribavirin in HCV-infected patients. PMID- 21971822 TI - Frequency of and predictors for patient-reported medical and medication errors in Switzerland. AB - OBJECTIVES: To analyse the frequency of and identify risk factors for patient reported medical errors in Switzerland. The joint effect of risk factors on error reporting probability was modelled for hypothetical patients. METHODS: A representative population sample of Swiss citizens (n = 1306) was surveyed as part of the Commonwealth Fund's 2010 lnternational Survey of the General Public's Views of their Health Care System's Performance in Eleven Countries. Data on personal background, utilisation of health care, coordination of care problems and reported errors were assessed. Logistic regression analysis was conducted to identify risk factors for patients' reports of medical mistakes and medication errors. RESULTS: 11.4% of participants reported at least one error in their care in the previous two years (8% medical errors, 5.3% medication errors). Poor coordination of care experiences was frequent. 7.8% experienced that test results or medical records were not available, 17.2% received conflicting information from care providers and 11.5% reported that tests were ordered although they had been done before. Age (OR = 0.98, p = 0.014), poor health (OR = 2.95, p = 0.007), utilisation of emergency care (OR = 2.45, p = 0.003), inpatient-stay (OR = 2.31, p = 0.010) and poor care coordination (OR = 5.43, p <0.001) are important predictors for reporting error. For high utilisers of care that unify multiple risk factors the probability that errors are reported rises up to p = 0.8. CONCLUSIONS: Patient safety remains a major challenge for the Swiss health care system. Despite the health related and economic burden associated with it, the widespread experience of medical error in some subpopulations also has the potential to erode trust in the health care system as a whole. PMID- 21971823 TI - Prospective evaluation of 68Ga-DOTA-NOC PET-CT in phaeochromocytoma and paraganglioma: preliminary results from a single centre study. AB - OBJECTIVE: To evaluate the role of (68)Ga-labelled [1, 4, 7, 10 tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid]-1-NaI(3)-Octreotide ((68)Ga DOTA-NOC) whole body positron emission tomography-computed tomography (PET-CT) as a functional imaging approach for phaeochromocytoma and paraganglioma. METHODS: Thirty-five unrelated patients (Median age-34.4 years; range: 15-71) were evaluated in this prospective study. PET-CT was performed after injection of 132 222 MBq of (68)Ga-DOTA-NOC. Images were evaluated by two experienced nuclear medicine physicians both qualitatively as well as quantitatively (standardised uptake value-SUVmax). In addition we compared the findings with (131)I Metaiodobenzylguanidine (MIBG) scintigraphy, which was available for 25 patients. Histopathology and/or conventional imaging with biochemical markers were taken as the reference standard. RESULTS: 44 lesions were detected on (68)Ga-DOTA-NOC PET CT imaging with an additional detection of 12 lesions not previously known, leading to a change in management of 6 patients. Sensitivity, specificity and accuracy were 100%, 85.7%, and 97.1% on a per patient basis and 100%, 85.7% and 98% on per lesion basis, respectively.(131)I MIBG scintigraphy was concordant with (68)Ga-DOTA-NOC PET-CT in 16 patients and false negative in 9 patients. CONCLUSION: (68)Ga-DOTA-NOC PET-CT is highly sensitive and specific for the detection of phaeochromoctyomas and paragangliomas. It seems better than (131)I MIBG scintigraphy for this purpose. KEY POINTS: * ( 68 ) Ga-DOTA-NOC PET-CT seems useful in patients with phaeochromocytoma and paraganglioma. * This prospective single centre study showed that it has high diagnostic accuracy. * (68) Ga-DOTA NOC PET-CT seems superior to (131) I-MIBG in these patients. PMID- 21971824 TI - What is the optimal b value in diffusion-weighted MR imaging to depict prostate cancer at 3T? AB - OBJECTIVE: To determine an optimal b value to visualise prostate cancer using diffusion-weighted magnetic resonance imaging at 3 T. METHODS: Forty one patients with biopsy proven prostate cancer underwent 3 T diffusion-weighted MRI performed with 5 b values (0, 1,000, 1,500, 2,000, 2,500 s/mm(2)) using a 16-channel coil. Best lesion visibility, the central gland-lesion (CG-L) and the peripheral zone lesion (PZ-L) contrast-to-noise ratio (CNR) were compared between different b value images, apparent diffusion coefficient (ADC) were measured. In a subset of 29 patients a high resolution b1,500 s/mm(2)diffusion-weighted sequence was additionally assessed. RESULTS: The b = 1,500 s/mm(2) and b = 2,000 s/mm(2) images provided the best lesion visibility respectively in 27/41 and in 10/41 patients. The highest CG-L and PZ-L CNR were obtained with b = 1,500 s/mm(2) (P < 0.0001). The mean ADC value calculated from 0 to 1,500 s/mm(2) b values in cancer lesions (ADC = 736 +/- 173 10(-6) mm(2)/s) was statistically significantly lower than in the peripheral zone (ADC = 1,338 +/- 256 10(-6) mm(2)/s, P < 0.0001) and in the central gland (ADC = 1,270 +/- 239 10(-6) mm(2)/s, P < 0.0001). The high resolution diffusion sequence was judged of better lesion visibility than (17/29) or equivalent to (6/29) the best images from the 5b sequence. CONCLUSION: At 3 T, prostate cancer lesions are best depicted with b = 1,500 s/mm(2) and b = 2,000 s/mm(2) images, b = 1,500 s/mm(2) high-resolution diffusion images improve the image quality and contrast. KEY POINTS: * Multiple b >= 1,000 s/mm ( 2 ) 3 T-DW Magnetic Resonance Imaging provides excellent prostate cancer depiction. * Prostate DWI and ADC maps are attainable at 3 T without endorectal coil. * Prostate cancer depiction is improved on high resolution b 1,500 s/mm ( 2 ) 3 T DWI. PMID- 21971825 TI - Friend of GATA suppresses the GATA-induced transcription of hepcidin in hepatocytes through a GATA-regulatory element in the HAMP promoter. AB - Hepcidin is an antimicrobial peptide hormone involved in the metabolism of iron, encoded for by the HAMP gene mainly in hepatocytes. It's expressed at lower levels in other cells such as the macrophages. The mechanisms that determine tissue-specific expression of hepcidin remain unclear. GATA- and its co-factor Friend of GATA (FOG) modulate the tissue-specific transcription of other genes involved in the metabolism of iron. GATA proteins are group of evolutionary conserved transcriptional regulators that bind to the consensus motif -WGATAR- in the promoter. We characterized a 1.3 kb fragment of the 5'-flanking sequence of the HAMP gene in Huh7 cells, which express HAMP. Transfection of 5'-deletions of the HAMP promoter in Huh7 cells revealed two regions, -932/-878 and -155/-96, that when deleted decreased promoter activity. Using site-directed mutations in the HAMP promoter region -155/-96 we identified two subregions, -138/-125 and 103/-98, which when mutated suppressed promoter activity by 70 and 90% respectively. Site -103/-98 with a sequence -TTATCT- to which endogenous GATA proteins 4 and 6 bind and transactivate HAMP is a GATA-regulatory element (RE). Mutation of the GATA-RE abrogated binding of GATA proteins 4 and 6 to the promoter and blunted the GATA transactivation of HAMP. FOG proteins 1 and 2 suppressed the endogenous and exogenous GATA activation of the HAMP promoter. We concluded that the GATA-RE, -TTATCT- in the HAMP promoter region -103/-98 is crucial for the GATA-4 and GATA-6 driven transcription of hepcidin in Huh7 cells and that FOG proteins moderate the transcription by suppressing the GATA transactivation of HAMP. PMID- 21971826 TI - Differentiation potential of human mesenchymal stem cells derived from adipose tissue and bone marrow to sinus node-like cells. AB - Adult mesenchymal stem cells (MSCs) hold great promise for the repair of heart defects. Both bone marrow-derived mesenchymal stem cells (BMSCs) and adipose tissue-derived stem cells (ASCs) are multipotent and may be induced by 5 azacytidine to differentiate into cardiomyocytes. However, the differentiation potential of human MSCs into sinus node-like cells has not been studied extensively. The aim of this study was to analyze the differences in proliferation and phenotype of ASCs and BMSCs from the same donors and to evaluate their capacity to differentiate into sinus node-like cells in vitro. Five passaged cells from bone marrow and adipose tissue were treated with 10 uM 5 azacytidine for 48 h and further cultured in complete medium for 4 weeks. A comparative study of cultured ASCs and BMSCs was carried out, and the morphological parameters, proliferative capacity, expression of surface markers and differentiation potential to sinus node-like cells were characterized. No morphologic differences were observed between ASCs and BMSCs. Flow cytometric analysis revealed that ASCs and BMSCs both expressed CD29, CD44, CD90 and CD105 and did not express CD34 and CD14, while CD49d, CD106 and CD34 were differentially expressed. Growth curves and doubling time determined with the Cell Counting Kit-8 (CCK-8) demonstrated that ASCs had a stronger proliferative ability than BMSCs. Histological immuofluorescence staining suggested that ASCs and BMSCs were capable of differentiating into sinus node-like cells and that the positive expression ratios of cTNI were higher in ASCs compared to BMSCs at 4 weeks. Expression of the HCN2 and HCN4 genes was detected by reverse transcriptase polymerase chain reaction, and the results revealed that the expression of the HCN genes appeared earlier in ASC-derived sinus node-like cells. ASCs expressed HCN2 and HCN4 shortly after induction with 5-azacytidine for 2 weeks, although BMSCs expressed these genes after 4 weeks. The expression levels of HCN2 and HCN4 mRNA in ASC-derived cells were higher compared to those of BMSCs at 4 weeks. In conclusion, ASCs may be a better candidate as a novel source of cell therapy in sinus bradycardia disorders than BMSCs. PMID- 21971827 TI - Comparison of polymeric siRNA nanocarriers in a murine LPS-activated macrophage cell line: gene silencing, toxicity and off-target gene expression. AB - PURPOSE: Tumor necrosis factor alpha (TNF-alpha) plays a key role in the progression of rheumatoid arthritis and is an important target for anti-rheumatic therapies. TNF-alpha expression can be silenced with small interfering RNA (siRNA), but efficacy is dependent on efficient and safe siRNA delivery vehicles. We aimed to identify polymeric nanocarriers for anti-TNF-alpha siRNA with optimal efficacy and minimal off-target effects in vitro. METHODS: TNF-alpha silencing with polymeric siRNA nanocarriers was compared in lipopolysaccharide-activated RAW 264.7 macrophages by real-time reverse transcription (RT)-PCR. Expression of non-target genes involved in inflammation, apoptosis, and cell cycle progression was determined by RT-PCR, toxicity evaluated by propidium iodide and annexin V staining. RESULTS: PAMAM dendrimers (G4 and G7) and dextran nanogels mediated remarkably high concentration-dependent gene silencing and low toxicity; dioleoyltrimethylammoniumpropane-modified poly(DL-lactide-co-glycolide acid) nanoparticles, thiolated, trimethylated chitosan and poly[(2 hydroxypropyl)methacrylamide 1-methyl-2-piperidine methanol] polyplexes were less efficient transfectants. There were minor changes in the regulation of off-target genes, mainly dependent on nanocarrier and siRNA concentration. CONCLUSIONS: Dextran nanogels and PAMAM dendrimers mediated high gene silencing with minor toxicity and off-target transcriptional changes and are therefore expected to be suitable siRNA delivery systems in vivo. PMID- 21971828 TI - The use of nano polymeric self-assemblies based on novel amphiphilic polymers for oral hydrophobic drug delivery. AB - PURPOSE: To investigate the use of nano self-assemblies formed by polyallylamine (PAA) modified with 5 or 10% mole fluorenylmethoxy carbonyl (Fmoc(5)/(10)), dimethylamino-1-naphthalenesulfonyl (Dansyl(5)/(10)) and 5% mole cholesteryl group (Ch(5)) for oral hydrophobic drug delivery. METHODS: Propofol, griseofulvin and prednisolone were loaded into amphiphilic PAAs. Particle size and morphology of drug-loaded self-assemblies were determined using photon correlation spectroscopy and transmission electron microscopy. Solubilising capacity, in vitro drug release and formulation stability were analysed by HPLC, and in vitro biocompatibility studies (haemolysis and cytotoxicity) were carried out on bovine erythrocytes and Caco-2 cells, respectively. Dansyl(10) and Ch(5) griseofulvin formulations were administered intra-gastrically to rats, and drug plasma levels were analysed by HPLC. RESULTS: Drug-encapsulated self-assemblies typically have hydrodynamic size of 300-400 nm. Dansyl(10) exhibited universal drug solubiliser property and had significantly improved prednisolone, griseofulvin and propofol solubility by 145, 557 and 224-fold, respectively. Fmoc polymers resulted in modest drug solubility improvement. These polymers were non-haemolytic, did not enhance cytotoxicity compared to unmodified PAA, and demonstrated significant increase in griseofulvin plasma concentration compared to griseofulvin in water after oral administration. CONCLUSIONS: Ch(5) and Dansyl(10) showed promising potential as nano-carriers for oral hydrophobic drug delivery. PMID- 21971829 TI - Liver cancer targeting of Doxorubicin with reduced distribution to the heart using hematoporphyrin-modified albumin nanoparticles in rats. AB - PURPOSE: To evaluate the usefulness of hematoporphyrin (HP)-modification of the surface of doxorubicin (DOX)-loaded bovine serum albumin (BSA) nanoparticles (NPs) in the liver cancer-selective delivery of DOX. METHODS: HP-modified NPs (HP NPs) were prepared by conjugation of amino groups on the surface of NPs with HP, a ligand for low density lipoprotein (LDL) receptors on the hepatoma cells. In vitro cellular accumulation of DOX, in vivo biodistribution of DOX, safety, and anti-tumor efficacy were evaluated for HP-NPs. RESULTS: Cytotoxicity and accumulation of DOX were in the order of HP-NPs>NPs>solution form (SOL). Cellular uptake from HP-NPs was proportional to the expression level of LDL receptors on the cells, indicating possible involvement of LDL receptor-mediated endocytosis (RME) in uptake. The "merit index," an AUC ratio of DOX in liver (target organ) to DOX in heart (major side effect organ) following iv administration of HP-NPs to hepatoma rats, was 132.5 and 4 times greater compared to SOL and NPs, respectively. The greatest suppression of body weight decrease and tumor size increase was observed for iv-administered HP-NPs in tumor-bearing mice. CONCLUSIONS: HP modification appears to be useful in selective delivery of NP loaded DOX to tumors. PMID- 21971831 TI - Crystal structure of the extracellular domain of human myelin protein zero. PMID- 21971832 TI - A ring-closing metathesis (RCM)-based approach to mycolactones A/B. AB - The total synthesis of the mycobacterial toxins mycolactones A/B (1 a/b) has been accomplished based on a strategy built around the construction of the mycolactone core through ring-closing metathesis. By employing the Grubbs second-generation catalyst, the 12-membered core macrocycle of mycolactones, with a functionalized C2 handle attached to C11, was obtained in 60-80 % yield. The C-linked upper side chain (comprising C12-C20) was completed by a highly efficient modified Suzuki coupling between C13 and C14, while the attachment of the C5-O-linked polyunsaturated acyl side chain was achieved by Yamaguchi esterification. Surprisingly, a diene containing a simple isopropyl group attached to C11 could not be induced to undergo ring-closing metathesis. By employing fluorescence microscopy and flow cytometry techniques, the synthetic mycolactones A/B (1 a/b) were demonstrated to display similar apoptosis-inducing and cytopathic effects as mycolactones A/B extracted from Mycobacterium ulcerans. In contrast, a simplified analogue with truncated upper and lower side chains was found to be inactive. PMID- 21971830 TI - Effects of relaxin on arterial dilation, remodeling, and mechanical properties. AB - Administering relaxin to conscious rats and humans elicits systemic and renal vasodilation. The molecular mechanisms vary according to the duration of relaxin exposure-so-called "rapid" (within minutes) or "sustained" (hours to days) vasodilatory responses-both being endothelium-dependent. Rapid responses are mediated by G(alphai/o) protein coupling to phosphoinositol-3 kinase/Akt (protein kinase B)-dependent phosphorylation and activation of nitric oxide synthase. Sustained responses are mediated by vascular endothelial and placental growth factors, as well as increases in arterial gelatinase activity. Thus, after hours or days of relaxin treatment, respectively, arterial MMP-9 or MMP-2 hydrolyze "big" endothelin (ET) at a gly-leu bond to form ET(1-32), which in turn activates the endothelial ET(B) receptor/nitric oxide vasodilatory pathway. Administration of relaxin to conscious rats also increases global systemic arterial compliance and passive compliance of select isolated blood vessels such as small renal arteries (SRA). The increase in SRA passive compliance is mediated by both geometric remodeling (outward) and compositional remodeling (decreased collagen). Relaxin-induced geometric remodeling has also been observed in brain parenchymal arteries, and this remodeling appears to be via the activation of peroxisome proliferator-activated receptor-gamma. Given the vasodilatory and arterial remodeling properties of relaxin, the hormone may have therapeutic potential in the settings of abnormal pregnancies, heart failure, and pathologies associated with stiffening of arteries. PMID- 21971833 TI - Stroke risk and NSAIDs: a systematic review of observational studies. AB - AIMS: To perform a quantitative systematic review of observational studies on the risk of stroke associated with the use of individual NSAIDs. METHODS AND RESULTS: Searches were conducted using the Medline database within PubMed (1990-2008). Observational cohort or case-control studies were eligible if reported on the risk of cardiovascular events associated with individual NSAIDs versus the nonuse of NSAIDs. We found 3193 articles, in which 75 were eligible for review and abstraction. Of the 75 articles, 6 reported relative risk (RR) of stroke. Data were abstracted into a database using a standardized entry form. Two authors assessed study quality, and discrepancies were resolved by consensus. The pooled RR of all subtypes of incident stroke was increased with the current use of rofecoxib (RR = 1.64, 95% CI = 1.15-2.33) and diclofenac (RR = 1.27, 95% CI = 1.08-1.48). The pooled estimates for naproxen, ibuprofen, and celecoxib were close to unity. The risk of ischemic stroke was also increased with rofecoxib (RR = 1.82, 95% CI = 1.09-3.04) and diclofenac (RR = 1.20, 95% CI = 0.99-1.45). Data were inadequate to estimate the pooled RR by dose and duration, for other individual NSAIDs or nonischemic stroke subtypes. CONCLUSION: This meta-analysis supports an increased risk of ischemic stroke with the current use of rofecoxib and diclofenac. Additional studies are required to evaluate most individual NSAIDS, the effect of dose and duration, and the subtypes of stroke. PMID- 21971834 TI - Self assembled tetranuclear Cu4(II), Ni4(II) [2 * 2] square grids and a dicopper(II) complex of heterocycle based polytopic ligands - Magnetic studies. AB - The ditopic ligand PyPzOAP (N-[(Z)-amino(pyridin-2-yl)methylidene]-5-methyl-1 (pyridin-2-yl)-1H-pyrazole-3-carbohydrazonic acid) and the polytopic ligand 2 PzCAP (N'(3),N'(5)-bis[(1E)-1-(pyridin-2-yl)ethylidene]-1H-pyrazole-3,5 dicarbohydrazide) were synthesized in situ by condensation of methyl imino picolinate with 5-methyl-1-(2-pyridyl) pyrazole-3-carbohydrazide and 2-acetyl pyridine with pyrazole-3,5-dicarbohydrazide respectively. The ligands PyPzOAP and PzOAP (reported earlier, Dalton Trans., 2007, 1229) self-assemble to form homoleptic [2 * 2] tetranuclear M(4) (M = Cu(II) and Ni(II)) square grids structures [Cu(4)(PyPzOAP)(4)](NO(3))(4) (1), [Cu(4)(PzOAP)(4)](ClO(4))(4) (2) and [Ni(4)(PyPzOAP)(4)](NO(3))(4).8H(2)O.2CH(3)CN (3). While the ligand 2-PzCAP forms a dicopper(II) complex [Cu(2)(2-PzCAP)(OH)(NO(3))(H(2)O)](NO(3)).2H(2)O (4). The complex 1 is a perfect square grid (a = 4.201 A), whereas, 2 and 3 are almost square grids. All these compounds have been characterized by X-ray structural analyses and variable temperature magnetic susceptibility measurements. EPR studies have also been carried out for complexes 1, 2 and 4. In the Cu(4) grid (1), all the Cu(II) centers are in a distorted octahedral environment with N(4)O(2) chromophore, while, in complex 2, all four Cu(II) centers have a square pyramidal environment with N(3)O(2) chromophore. In complex 3, all four Ni(II) centers have distorted octahedral geometry with N(4)O(2) chromophore. In compound 4, the Cu(II) centers are in square pyramidal environment with N(3)O(2) chromophore. The magnetic properties of compounds 1 and 2 show the presence of intramolecular ferromagnetic exchange interaction (J = 5.88 cm(-1) for 1 and 4.78 cm(-1) for 2). The complex 3 shows weak intramolecular antiferromagnetic interaction (J = -4.02 cm(-1)). While, complex 4, shows strong antiferromagnetic behavior (J = -443 cm(-1)). PMID- 21971835 TI - A healthy bonus. AB - Texas physicians who participate in the Blue Cross and Blue Shield Bridges to Excellence quality improvement program have an opportunity to improve patient care and at the same time increase revenues for their practices. The program allows Blue Cross to reward good physicians, improve the care its beneficiaries receive, and lower costs for the company and for employers who pay for coverage. PMID- 21971836 TI - Drug shortage. AB - Calcium gluconate, neostigmine, propofol, epinephrine, furosemide, and a host of sterile injectables, as well as antibiotics and other medications, are among the drugs on an expansive list of shortages tracked by the U.S. Food and Drug Administration (FDA). A record 246 drugs were in short supply as of June, according to FDA. That figure has many Texas physicians worried about potential risks to patient safety and quality of care. PMID- 21971837 TI - Treating your own. AB - Giving a staff member a flu shot or writing your spouse a prescription for pain medication may not seem like a big deal. But if you fail to maintain a medical record for the employee, or if your spouse gets hooked on a controlled substance, you could be in hot water. Texas Medical Board Executive Director Mari Robinson, JD, says it's not illegal for physicians to treat family members, friends, and employees, but doing so poses risks. PMID- 21971838 TI - Getting coverage. AB - The Pre-existing Condition Insurance Plan, created under the Affordable Care Act, is a new federal program that provides affordable comprehensive health coverage for those with preexisting conditions. The plan was launched in Texas in August 2010 and recently lowered monthly premiums and eased eligibility requirements. PMID- 21971839 TI - Legal backup. AB - The Texas Medical Association regularly collaborates with the Litigation Center of the American Medical Association and State Medical Societies to present a united front in legal cases that might affect the practice of medicine in Texas and even the nation. The Litigation Center has been the medical profession's voice in legal proceedings across the country for 16 years by providing physicians with assistance and expertise. PMID- 21971840 TI - Managing medicaid. AB - Medicaid beneficiaries in the Lower Rio Grande Valley and rural Texas who have little or no experience with HMOs soon will become closely acquainted with them. Under Senate Bill 7, which passed in this summer's special session, the Texas Legislature mandated statewide Medicaid managed care, which previously was limited to large urban areas. The move is one of dozens of cost-cutting initiatives included in SB 7. PMID- 21971841 TI - Cancer incidence and mortality in Texas and the United States: an overview. AB - The US Centers for Disease Control and Prevention releases annually an updated US Cancer Statistics report containing incidence and mortality data for all states and aggregate US data that allow for more meaningful comparisons across populations and geographic regions than do the number of new cases and deaths. This article examines major Texas findings from the most recent report (for the 5 year period 2003-2007) and compares Texas and United States. PMID- 21971843 TI - Myocardial ischemia analysis based on electrocardiogram QRS complex. AB - Electrocardiogram (ECG) is an economic, convenient, and non-invasive detecting tool in myocardial ischemia (MI), and its clinical appearance is mainly exhibited by the changes in ST-T complex. Recently, QRS complex characters were proposed to analyze MI by more and more researchers. In this paper, various QRS complex characters were extracted in ECG signals, and their relationship was analyzed systematically. As a result, these characters were divided into two groups, and there existed good relationship among them for each group, while the poor relationship between the groups. Then these QRS complex characters were applied for statistical analysis on MI, and five characters had significant differences after ECG recording verification, which were: QRS upward and downward slopes, transient heart rate, angle R and angle Q. On the other hand, these QRS complex characters were analyzed in frequency domain. Experimental results showed that the frequency features of RR interval series (Heart Rate Variability, HRV), and QRS barycenter sequence had significant differences between MI states and normal states. Moreover, QRS barycenter sequence performed better. PMID- 21971842 TI - IDH1/2 gene status defines the prognosis and molecular profiles in patients with grade III gliomas. AB - BACKGROUND: The discovery of isocitrate dehydrogenase 1 and 2 gene (IDH1/2) mutations has enabled grade III glioma to be divided into mutated and wild-type IDH1/2 groups, which are known to carry different prognosis and molecular features. However, detailed subgroup analysis of grade III glioma is limited. To address this, we investigated molecular and prognostic features of grade III glioma with and without IDH1/2 mutation. METHODS: We retrospectively analyzed 115 grade III glioma patients. Clinical parameters were obtained from medical records. The mutation of IDH1/2 and TP53 was analyzed by direct sequencing. O(6) methylguanine methyltransferase gene (MGMT) gene promoter methylation status was determined by methylation-specific polymerase chain reaction. Detection of chromosome copy number changes of 1p, 7p (EGFR), 9p (CDKN2A), 10q (PTEN), and 19q was carried out by multiple ligation-dependent probe amplification. Patients were divided into two groups, mutated IDH1/2 and wild-type IDH1/2, for correlation with the factors analyzed. RESULTS: In our series, as previously reported, IDH1/2 mutation was an independent prognostic marker for improved progression-free and overall survival (OS) (P < 0.0001 and P < 0.0001, respectively) in patients with grade III gliomas. Subgroup analysis found that incomplete resection, 7p gain, and TP53 mutation were independent prognostic factors of poor outcome in grade III glioma patients with mutated IDH1/2 (P = 0.0092, P = 0.015 and P = 0.026, respectively), while there were none in patients with wild-type IDH1/2. CONCLUSIONS: IDH1/2 gene status was significantly associated with prognosis in grade III gliomas. Subgroup analysis found that poor prognostic factors existed even in patients with IDH1/2 mutation. PMID- 21971844 TI - How to uncoil your partner--"mating songs" in giant pill-millipedes (Diplopoda: Sphaerotheriida). AB - The stridulation of the giant pill-millipede genus Sphaerotherium from South Africa, one of only three groups of millipedes that produce sounds, was studied. One hundred one stridulation series of a total of nine different species (Sphaerotherium dorsaloide, Sphaerotherium hanstroemi, Sphaerotherium mahaium, Sphaerotherium similare, Sphaerotherium punctulatum, Sphaerotherium convexitarsum, Sphaerotherium dorsale, Sphaerotherium rotundatum, and Sphaerotherium perbrincki) were analyzed. Stridulation sounds are produced only with a special field of ribs on the posterior surface of the posterior telopod, which is actively moved over a field of sclerotized nubs on the inner margin of the anal shield. The Sphaerotherium male usually stridulates only when in contact with a female to initiate mating. This seems to prevent the female from volvating into a ball or stimulate the female to uncoil when already rolled in. The sound analyzes revealed a broad frequency spectrum in all stridulation sounds produced, without obvious differences in frequency distribution among species. However, the temporal pattern of the stridulation varies greatly between species and seems to be species-specific, arguing for a species recognition function of the stridulation during courtship behavior. A single species (S. punctulatum) was found to stridulate during mating while three species also show postcopulatory stridulation. Apparently, pill-millipedes are not capable of acoustic perception, as no hearing organs are known, indicating that the communication is mainly based on perception of temporal vibration patterns, and not of the acoustic signal itself. The need to overcome the rolling-in reflex of the female is developed as a hypothesis why stridulation exists only in millipedes able to coil into a ball, and apparently evolved four times independently in the superorder Oniscomorpha. PMID- 21971845 TI - Myocardial area at risk after ST-elevation myocardial infarction measured with the late gadolinium enhancement after scar remodeling and T2-weighted cardiac magnetic resonance imaging. AB - To evaluate the myocardial area at risk (AAR) measured by the endocardial surface area (ESA) method on late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) when applied after scar remodeling (3 months after index infarction) compared to T2-weighted CMR imaging. One hundred and sixty nine patients with ST-elevation myocardial infarction, treated with primary percutaneous coronary intervention, underwent one CMR within 1 week after index treatment to determine the AAR with T2-weighted imaging and a second scan 3 months after to measure AAR with the ESA method. There was a moderate correlation between the two methods (r = 0.86; P < 0.001). The AAR was significantly higher measured with T2-weighted imaging than with the ESA methods (32 +/- 11% of left ventricle (LV) vs. 26 +/- 10%LV; P < 0.001). The mean difference was 6 +/- 6%LV. Furthermore, the mean difference between the two methods was statistical higher in the patients with myocardial salvage index >=0.90 than in the remaining patients (9 +/- 8%LV vs. 6 +/- 5%LV; P = 0.02). The ESA method performed after scar remodeling (3 months following STEMI) yields significantly lower AAR's and myocardial salvage indices compared to the T2-weighted method. Therefore, T2 weighted CMR plus LGE is the method of choice to assess AAR and myocardial salvage index using CMR. However, the ESA method is an easy and valid method for determining AAR, which can be used in settings where T2-weighted imaging has not been obtained in the acute phase. PMID- 21971846 TI - Transfection by electroporation. AB - Electroporation--the use of high-voltage electric shocks to introduce DNA into cells--can be used with most cell types, yields a high frequency of both stable transformation and transient gene expression, and, because it requires fewer steps, can be easier than alternate techniques. This unit describes electroporation of mammalian cells, including ES cells for the preparation of knock-out, knock-in, and transgenic mice. Protocols are described for the use of electroporation in vivo to perform gene therapy for cancer therapy and DNA vaccination. Also described are modifications for preparation and transfection of plant protoplasts. PMID- 21971847 TI - High-speed multineuron calcium imaging using Nipkow-type confocal microscopy. AB - Conventional confocal and two-photon microscopy scan the field of view sequentially with single-point laser illumination. This raster-scanning method constrains video speeds to tens of frames per second, which are too slow to capture the temporal patterns of fast electrical events initiated by neurons. Nipkow-type spinning-disk confocal microscopy resolves this problem by the use of multiple laser beams. We describe experimental procedures for functional multineuron calcium imaging (fMCI) based on Nipkow-disk confocal microscopy, which enables us to monitor the activities of hundreds of neurons en masse at a cellular resolution at up to 2000 fps. PMID- 21971848 TI - Production of recombinant adeno-associated viral vectors and use in in vitro and in vivo administration. AB - Adeno-associated virus is a nonpathogenic human virus that has been developed into a gene-delivery vector due to its high efficiency of infection for many different cell types and its ability to persist and lead to long-term gene expression. This unit describes efficient methods to generate high-titer, research-grade, adenovirus-free recombinant single-stranded and self complementary adeno-associated virus in various serotypes, along with methods to quantify the viral vectors. Two detailed methods are provided for viral vector delivery into the rodent brain and spinal cord, and for histological detection of transgene expression of GFP. PMID- 21971849 TI - Alphaviruses: Semliki forest virus and Sindbis virus vectors for gene transfer into neurons. AB - Alphaviral vectors based on Semliki Forest virus and Sindbis virus infect many host cell types, causing rapid and high-level transgene expression. In the CNS, Semliki Forest virus and Sindbis virus exhibit an outstanding preference for neurons rather than glial cells, compared to other viruses. Generation of high titer virus stocks is rapid (less than two days) and typically requires biosafety level 1 or 2 containment. Wild-type vectors are cytotoxic, permitting short-term transgene expression. However, mutant vectors with decreased cytotoxicity, to prolong host cell survival, have been developed. They also increase transgene expression and cellular co-infection, permitting heteromeric protein expression in individual cells. In addition, mutants with temperature-dependent control of transgene expression and altered host cell preference to target interneurons and astrocytes rather than principal neurons are available. Other alphavirus vectors based on Venezuelan equine encephalitis and Eastern equine encephalitis virus replicons have been engineered, too. Alphavirus vectors have been successfully used not only in neuroscience, but also for other applications including drug discovery, structural biology, vaccine development, and cancer therapy. PMID- 21971850 TI - A mouse model for observational fear learning and the empathetic response. AB - Research on observed fear and its relation to human mental disorders has been hampered by the lack of a suitable animal model. The empathetic response, which is impaired in various mental disorders, requires the ability to recognize the emotions and feelings of others. Due to the lack of a robust behavioral assay system, studies of empathy in laboratory animals have been absent from the literature. This unit describes a protocol for assessing social observational fear learning as a precursor of empathy in the mouse. In this assay, the observer animal is conditioned for context-dependent fear by observing the behavior of the demonstrator animal receiving aversive stimuli. The magnitude of the fear response of the observer is positively influenced by the animal's familiarity with the demonstrator. This indicates that the degree of familiarity, and its relationship to empathy, can be modeled in an animal system by a method relevant to human disease. PMID- 21971851 TI - [Brazilian College of Surgeons : the present status]. PMID- 21971852 TI - Descriptive study of breast cancer cases in Goiania between 1989 and 2003. AB - OBJECTIVE: To describe cases of breast cancer in women living in Goiania from 1989-2003. METHODS: We conducted a retrospective, descriptive stud, which included all cases of breast cancer occurring in residents of Goiania, identified by the Population-Based Cancer Registry of Goiania (RCBPGO) in the period from 1989 to 2003. The variables were: age, method of diagnosis, topographic location, morphology and extent of breast cancer. We used frequencies and percentage rates, and Poisson regression to determine the annual percentage change (APC). RESULTS: We identified 3204 cases of breast cancer. The most frequent topographic location was the superior-lateral quadrant (53.7%). Infiltrating ductal carcinoma (IDC) was the most frequent, with 2582 cases (80.6%), followed by infiltrating lobular carcinoma (ILC), with 155 cases (4.8%). There was a significant increase of both the IDC and the ILC, with APCs of 11.0% and 15.4%, respectively. The ratio between IDC and ILC was not influenced by age (p = 0.98). As for tumor extent at diagnosis, 45.6% were located in the breast, and the APC was 16.1% (CI = 12.4 to 20.0, p <0.001). There was a trend of APC reduction of metastatic cases (-3.8, CI = -8.6 to 1.2, p = 0.12). CONCLUSION: The topographical location and histological type of breast cancer in the city of Goiania followed the pattern of other countries. The main morphological types were not influenced by age. There was a large increase in initial cases. PMID- 21971853 TI - Improved double-fuse technique for post-bariatric brachioplasty. AB - OBJECTIVE: To evaluate the use of modified brachioplasty, investigating in late postoperative complications and satisfaction with the outcome, in women previously submitted to bariatric surgery. METHODS: The population (N = 18, age 49.2 +/- 11.3 years), which had undergone brachioplasty 25.2 +/- 11.9 months after the bariatric procedure, was contacted after 31.7 +/- 38.8 additional months. Surgical complications and satisfaction with the operation were estimated by interviews, including a questionnaire designed for this purpose. RESULTS: pre bariatric body mass index (BMI) was 57.1 +/- 11.1 kg / m(2), being 28.3 +/- 6.0 kg/m(2) before the brachioplasty, without significant changes thereafter. Three minor surgical complications were recorded (3 / 18, 16.7%), namely, temporary paresthesia, seroma and small imperfection of the scar. The satisfaction rate was approximately 90%, with the three most rewarding results for the patients being the ease of dressing (P = 0.01), decreased weight of the arm (P = 0.03) and absence of edema (P = 0.04). There was a negative correlation between severe weight loss and degree of satisfaction, however, no patients regretted the procedure. CONCLUSION: the modified brachioplasty was successful in cases with severe brachial ptosis with possible extension to the chest. The study confirmed functional and aesthetic benefits, and thanks to the technique applied, most of the complications and disappointments could be avoided. PMID- 21971854 TI - Total thyroidectomy for benign thyroid diseases. AB - OBJECTIVE: To review the indications for total thyroidectomy as the preferred option in certain benign diseases of the thyroid in order to prevent recurrence or future reoperations. METHODS: A retrospective study of patients with benign thyroid diseases, carried out from January 1997 to December 2009, analyzing the data relating to age, surgical treatment and postoperative evolution. RESULTS: The mean age was 51.8 years (21/77), with the highest incidence in the fifth and sixth decades of life, with 34 (51.5%) patients. The most common preoperative diagnosis was nontoxic multinodular goiter, of which seven were also intrathoracic, followed by autoimmune thyroiditis; recurrent goiter occurred in 11 cases. Multinodular goiter was found in 37 (56.1%) patients, autoimmune thyroiditis in 22 (33.3%), follicular adenoma isolated in five (7.6%), Hurthle cell adenoma in two (3.0%). Sixteen patients (24.2%) had more than one histopathological diagnosis. Permanent injury of the recurrent nerve was observed in one patient (1.5%). There was no case of permanent hypoparathyroidism. There was no operative mortality. CONCLUSION: Total thyroidectomy is an operation that can be safely performed, with low incidence of permanent complications, which allows one to broaden its indications in various benign thyroid diseases, thus avoiding future recurrences and reoperations. PMID- 21971855 TI - Local effectiveness and complications of neoadjuvant therapy in esophageal squamous cell carcinoma: radiotherapy versus chemoradiotherapy. AB - OBJECTIVE: To evaluate tumor responses to neoadjuvant therapy, according to the histopathological findings of surgical specimens of patients operated and treated for squamous cell carcinoma of the middle third and distal esophagus. METHODS: We conducted a retrospective nonrandomized study including 97 patients distributed as follows: Group I - 81 (83.5%) underwent neoadjuvant radiation therapy, and group II - 16 (16.5%) underwent neoadjuvant radiotherapy and chemotherapy. A third group of 26 patients undergoing esophagectomy alone was used for comparison of postoperative complications. The characteristics of each patient (age, gender and race), tumor site, staging, and histological evaluation of treatment modalities were reviewed and analyzed. Tumor response to neoadjuvant therapy was evaluated by histopathology of the specimen. RESULTS: There was no statistically significant differences regarding race, gender, age, staging and postoperative complications in patients in the three groups. Patients undergoing radiotherapy and neoadjuvant chemotherapy showed more satisfactory tumor reduction, with improved local efficacy when compared to the group only submitted to neoadjuvant radiotherapy. CONCLUSION: The study suggests that radiotherapy combined with chemotherapy was more efficient in reducing tumor site when compared to the group treated with radiotherapy. In addition, neoadjuvant therapy did not increase the postoperative complications when compared to patients undergoing surgery alone. PMID- 21971856 TI - Weight loss eight years after gastric bypass. AB - OBJECTIVE: To evaluate the effectiveness of banded Roux-en-Y gastric bypass in promoting weight loss after an eight-year follow-up. METHODS: Two hundred and eleven obese patients underwent Roux-en-Y gastric bypass with banding by the same surgical team. The study design was longitudinal, prospective and descriptive. The analysis of weight decrease in the postoperative period was based on the loss of excess weight in percentage and BMI. Failure was considered when patients lost <50% of excess weight. RESULTS: The loss of follow-up was 36.5%, therefore, 134 patients were included in this study. The loss of excess weight in global average rate in the postoperative period was: 67.6 +/- 14.9% in the first year, 72.6 +/- 14.9% in the second year, 69.7 +/- 15.1% in fifth year and 66.8 +/- 7.6 in eight years. Surgical treatment failure occurred in 15 patients (7.1%) over the period. CONCLUSION: Banded Roux-en-Y gastric bypass was effective in promoting and sustaining weight loss in the long term, with low failure rates. PMID- 21971857 TI - Type IV Borrmann gastric adenocarcinoma: analysis of curative resection results. AB - OBJECTIVE: To evaluate the results obtained with curative resection of Borrmann IV gastric adenocarcinoma (B IV) through the analysis of clinical, surgical and pathological data, identifying which of these prognostic factors were associated with survival. METHODS: We retrospectively analyzed 123 patients with B IV gastric adenocarcinoma undergoing surgical treatment at the Department of the pelvic-abdominal surgeries of the National Cancer Institute (INCA) from January 1997 to December 2005. The group undergoing curative resection was examined for various prognostic factors regarding overall survival. RESULTS: Of the 123 patients studied, 68 underwent gastrectomy, 52 (42.3%) with curative intent and 16 (13%) palliative resection, while 55 (44.7%) had disease not subject to resection. Three postoperative deaths followed the curative resection, constituting a mortality rate of 5.76%. In nine (17.3%) patients there were technical complications, and esophagojejunal fistula seven cases, the most frequent. All technical complications and deaths occurred after total gastrectomy, which was the most commonly performed curative resection type in this series. The most common pattern of recurrence was peritoneal carcinomatosis. The location of the tumor, lymph node metastasis, lymphatic invasion and pathological staging were considered significant prognostic factors. The median survival time was 29 months, with a rate of five-year survival of 33% in patients undergoing curative resection. CONCLUSION: The curative resection of B IV gastric adenocarcinoma had a positive impact on survival of patients with the disease in stages IB, II and III, with up to 15 lymph nodes (pN2) and localized type. PMID- 21971858 TI - Treatment of rectal adenocarcinoma by laparoscopy and conventional route: a brazilian comparative study on operative time, postoperative complications, oncological radicality and survival. AB - OBJECTIVE: To compare two surgical routes (laparoscopic and conventional) for the treatment of rectal cancer with regard to postoperative complications, oncological radicality and survival. METHODS: This is a retrospective study of 84 patients with rectal cancer who were admitted to the Barretos Cancer Hospital between 2000 and 2003. Only individuals who underwent elective operations with curative intent were included. The surgical approach was subjectively chosen rather than by location of the tumor. RESULTS: The laparoscopic access was used by 50% of patients. There was no difference (P> 0.05) between the two groups regarding age, sex, topography, staging, neoadjuvant and adjuvant treatment, number of dissected lymph nodes, size of surgical specimen, surgical margins, blood transfusions, postoperative complication rates, hospital stay and overall survival. Surgical time was longer in the laparoscopic group (median: 210x127, 5 min, P <0.001). A reduction in surgical time was noted with the increasing number of laparoscopies performed by the team (rho: -0.387, P = 0.020). CONCLUSION: The laparoscopic and conventional routes, for the treatment of rectal cancer, were equivalent with respect to postoperative complications, oncological radicality and survival. However, the operative time was longer in the laparoscopic group. PMID- 21971859 TI - Liver and peritoneal biopsy by laparoscopy or notes in pigs: comparison of operative parameters and postoperative evolution. AB - OBJECTIVE: To evaluate the impact of NOTES compared to laparoscopic surgery, through the analysis of physiological parameters as well as surgical complications and postoperative outcome, for liver biopsy. METHODS: 12 female pigs were divided into two groups: laparoscopy group (GLap) and NOTES group (GNote). The animals underwent liver biopsy by peritoneal laparoscopy or transvaginal endoscopy. The respiratory rate, heart rate, O2 saturation and expiratory concentrations of CO2 were recorded every 10 minutes. In the seventh postoperative day, the animals underwent laparotomy for evaluation of intra abdominal complications. RESULTS: Most of the animals showed weight loss after the procedure, however in no case more than 5%. There was no difference in percentage change in weight between the groups (p = 0.7535). Also, no differences were observed when comparing the averages of ETCO2 (p = 0.4762), and average heart rate (p = 0.6035). However, the GLap showed higher respiratory rate than the GNote (p = 0.0043), as well as the average O2 saturation (p = 0.0080). However, no animal showed SatO2 less than 87% and this difference was not considered clinically significant. Only one GNote animal presented with an operative complication. CONCLUSION: NOTES is associated with physiological parameters similar to those found in operative laparoscopy. Performing transvaginal peritonioscopy is not associated with increased postoperative complications when compared to laparoscopy. PMID- 21971860 TI - Action of tacrolimus in arginine induced experimental acute pancreatitis. AB - OBJECTIVE: To determine whether tacrolimus administered to rats, in the presence of pancreatitis induced by L-Arginine, interferes with the serum levels of amylase and glucose and the histological pattern of the pancreatic parenchyma. METHODS: Forty Wistar rats were divided into four groups with 10 rats each: control group (C), tacrolimus group (T), pancreatitis group (P) and pancreatitis tacrolimus group (PT). We evaluated serum levels of amylase, glucose, and tacrolimus and made histological assessments of the pancreas. Induction of pancreatitis was made by inoculation of L-Arginine at a dose of 500 mg/100g body weight intraperitoneally, and tacrolimus treatment at a dose of 1ig/kg subcutaneously for four days. RESULTS: Serum amylase was higher (p = 0.0000) in groups PT, P and T than in the control group. The PT group mean was higher (p = 0.0009) than in the T group, but did not differ (p = 0.6802) from the average of the P group. There was no difference between groups P and T (p = 0.2568). Neither in mean blood glucose between the groups (p = 0.4920); serum levels of tacrolimus were similar in PT and T groups (p = 0.7112). There were no histological changes in groups T and C and no hemorrhage in the pancreas of rats in groups P and PT. In group P, there was no edema in 30%, mild edema in 20% and in 50%, moderate; as for inflammatory infiltration, it was moderate in 80% and absent in 20%, and atrophy of the parenchyma was moderate in 60% and severe in 40%. In the PT group, there was edema, inflammatory infiltration or atrophy in the pancreas in all rats. CONCLUSION: Treatment with Tacrolimus induced an increase in serum amylase in normal mice, but did not affect blood glucose or the histological pattern of the pancreatic parenchyma. In the presence of pancreatitis induced by L-Arginine tacrolimus induced edema, inflammatory infiltration and more severe atrophy in the pancreatic parenchyma. PMID- 21971861 TI - Effect of anti-TNF-alpha on peritoneal endometrial implants of rats. AB - OBJECTIVE: To evaluate the effect of anti-TNF-alpha in the treatment of endometrial implants in the peritoneum of rats. METHODS: Endometrial implants were surgically induced in 120 female Wistar-Albino rats. The animals were randomly divided into four groups. Group C (n = 36) received an intraperitoneal injection of 0.2 ml of saline. Group L (n = 41) received a subcutaneous injection of 1mg/kg of leuprolide. Group I5 (n = 20) received a subcutaneous injection of 5mg/kg of monoclonal anti-tumor necrosis factor (TNF) a (infliximab). Group I10 (n = 20) received a subcutaneous injection of 10mg/kg of infliximab. The rats were sacrificed after 21 days to assess the size of the implants and the expression of TNF. RESULTS: Treatment with leuprolide (group L) promoted an absolute reduction in the surface area of the implant when compared with group C (+14 mm vs. 0mm, p = 0.013) and group I10 (+14 mm vs. +5 Mm, p = 0.018). Likewise, a percentage reduction of surface area of the implant was observed comparing group L with group C (+33.3% vs. 0%, p = 0.005) and group I10 (+33.3% vs. +18.3%, p = 0.027). Treatment with infliximab was not able to decrease the surface area of the implants when compared with group C. The expression of TNF alpha in groups L, I5 and I10 was lower than in group C (505.6 mm(2) vs. 660.5 mm(2) vs. 317.2 mm(2) vs. 2519.3 mm(2), respectively; p <0.001). CONCLUSION: The anti-TNF-alpha therapy reduced the expression of TNF-alpha in endometriotic implants, but did not reduce the surface area of the lesion. PMID- 21971862 TI - [Management of high grade squamous intraepithelial lesion of the cervix of adult women]. AB - Cervical cancer is the second most common cancer among women worldwide, despite having great potential for prevention and cure when early diagnosed and treated, which can reduce the mortality rate among the affected. Since there is no consensus among the therapeutic measures in high grade cervical squamous intraepithelial lesions (HGSIL), we discuss its approach when dealing with adult women who have HGSIL and the follow-up after the adopted procedure. We performed electronic searches of MEDLINE (through PubMed), National Guidelines Clearinghouse, Google Scholar and Lilacs. The guidelines identified were evaluated according to their validity and recommendations. In relation to after care, the European use cytology every 6 months, the Australians, cytology and colposcopy every 6 months, the Americans advocate the realization of hybrid capture in six to 12 months or cytology every 6 months. The Brazilian Guidelines Project, on its turn, recommends that clinical reassessments and Pap smear should be performed every three or four months during the first two years of follow-up. Studies comparing the method "See and Treat" with the three steps one (histology, colposcopy, biopsy) concluded that the latter is indicated for women ASCUS/LSIL before undergoing the excision of the transformation zone (ETZ), while the "View and Treat" is indicated in women with proven HGSIL in cytology and suggestive in colposcopy, because it presents advantages such as low cost and immediate solution. All the guidelines are unanimous in stating that when facing proven HGSIL, excision of the injury through ablation or conization or ETZ is indicated. PMID- 21971863 TI - Evaluation of training and professional expectations of surgery residents. AB - Residency programs, especially in surgery, have been undergoing constant changes, not only in our country, but also internationally. Due to the depreciation of medical specialties and their lowering compensation, expectations and profile of residents in surgical fields are changing. The assessment of attitudes, experience in training and professional expectations among residents is an important topic. Recent international studies published in the area demonstrate this fact. It is worth noting the absence of similar studies in our country, as well as others. This study aims to assess the residents of the area of surgery, through a questionnaire, their attitudes, experiences during training and professional expectations. We applied and analyzed questionnaires adapted and translated into Portuguese to 50 professionals of both sexes and different years of residence. The results of this study showed high satisfaction with the specialty, but large financial concern and conflicting opinions about the future of the specialty. PMID- 21971864 TI - [Multiple focal nodular hyperplasia of the liver: mixed hyperplastic and adenomatous subtype]. AB - Focal Nodular Hyperplasia is a benign lesion of the liver, which usually presents with one or two localizations. We report the uncommon case of a 51-year-old female who presents with right upper quadrant pain that worsened in the previous month, without association with feeding. Four hepatic lesions were evidenced at Computerized tomography, the largest being of 8 cm in diameter, of atypical behavior. She was submitted to hepatic segmentectomy of the segment III. The pathologic diagnosis returned focal nodular hyperplasia mixed hyperplastic and adenomatous sub-type. The patient had a good postoperative evolution and is in ambulatory follow-up. PMID- 21971865 TI - [Duodenal gangliocytic paraganglioma]. AB - We present a case of a 42-year-old man with abdominal pain, obstructive jaundice and a mass in the second portion of the duodenum, near the papillary region. The patient was operated and the histological study of the specimen returned duodenal gangliocytic paraganglioma (a rare submucosal benign tumor of the duodenum). We also describe, after revision of the literature, the pathology, the diagnosis and its treatment. PMID- 21971866 TI - Bag3 promotes resistance to apoptosis through Bcl-2 family members in non-small cell lung cancer. AB - In non-small cell lung cancer (NSCLC) certain molecular characteristics, which are related to molecular alterations have been investigated. These are responsible for both the initiation and maintenance of the malignancy in lung cancer. The aim of this study was to evaluate the influence of Bag3 (Bcl-2 associated athanogene 3) in the regulation of apoptosis on NSCLC. Bag3 and Hsp70 expression were examined by immunohistochemistry to confirm their potential roles in the prevalence of NSCLC. We also established human normal bronchial epithelial cells and HOP-62 cell line as the model to analyze cell apoptosis and the expression of Hsp70, Bcl-XL and Bcl-2, which were affected by Bag3. In this study, we found that Bag3 and Hsp70 are highly expressed in few tissues and cell lines of NSCLC. Bag3 inhibits apoptosis in human normal bronchial epithelial cell lines and sustain the survival of NSCLC cells. Bag3, Hsp70, Bcl-XL and Bcl-2 are up-regulated in NSCLC cell lines. At the same time, the silencing of Bag3 results in diminishing protein levels of Bcl-XL and Bcl-2. The results of immunoprecipitation identified that Bag3 could interact with Hsp70, Bcl-XL and Bcl-2 NSCLC cells directly or indirectly. We conclude that NSCLC cells were protected from apoptosis through increasing Bag3 expression and consequently promoted the expression of Bcl-XL and Bcl-2. PMID- 21971867 TI - Neuropeptide Y Y1 receptor hippocampal overexpression via viral vectors is associated with modest anxiolytic-like and proconvulsant effects in mice. AB - Neuropeptide Y (NPY) exerts anxiolytic- and antidepressant-like effects in rodents that appear to be mediated via Y1 receptors. Gene therapy using recombinant viral vectors to induce overexpression of NPY in the hippocampus or amygdala has previously been shown to confer anxiolytic-like effect in rodents. The present study explored an alternative and more specific approach: overexpression of Y1 receptors. Using a recombinant adeno-associated viral vector (rAAV) encoding the Y1 gene (rAAV-Y1), we, for the first time, induced overexpression of functional transgene Y1 receptors in the hippocampus of adult mice and tested the animals in anxiety- and depression-like behavior. Hippocampal Y1 receptors have been suggested to mediate seizure-promoting effect, so the effects of rAAV-induced Y1 receptor overexpression were also tested in kainate induced seizures. Y1 receptor transgene overexpression was found to be associated with modest anxiolytic-like effect in the open field and elevated plus maze tests, but no effect was seen on depression-like behavior using the tail suspension and forced swim tests. However, the rAAV-Y1 vector modestly aggravated kainate-induced seizures. These data indicate that rAAV-induced overexpression of Y1 receptors in the hippocampus could confer anxiolytic-like effect accompanied by a moderate proconvulsant adverse effect. Further studies are clearly needed to determine whether Y1 gene therapy might have a future role in the treatment of anxiety disorders. PMID- 21971869 TI - Communicating diabetes best practices to clients: a preliminary investigation of educator perspectives. AB - PURPOSE: The majority of people with type 2 diabetes do not meet dietary and physical activity recommendations. It is not well understood how diabetes educators translate diet and physical guidelines for their clients and if diabetes educators have sufficient resources to promote healthy eating and physical activity. This research addressed these questions through exploratory qualitative interviews. METHOD: A total of 13 diabetes educators who work in Alberta, Canada, were interviewed. RESULTS: The reasons for lack of client uptake of lifestyle recommendations were complex and interwoven. The strongest theme to emerge was the clients' prior knowledge and skills affecting their ability to uptake knowledge. However, educators recognized that clients are affected by social, environmental, cultural, and personal factors. CONCLUSIONS: Health system and societal issues cause a cascade effect resulting in difficulties for both educators and clients. To achieve appropriate treatment of type 2 diabetes, changes need to occur at a health systems level. PMID- 21971868 TI - Tiam1, overexpressed in most malignancies, is a novel tumor biomarker. AB - T lymphoma invasion and metastasis 1 (Tiam1) is a guanine nucleotide exchange factor (GNEF) family member, and is considered to be involved in many important cellular processes and oncogenesis. In this study, we investigated Tiam1 expression differences between normal tissue and malignant tissue using tissue microarray (TMA), and further studied the Tiam1 mRNA and protein level in 9 hepatoma lines. Forty-nine tumor tissue and 47 normal tissue samples were detected via TMA by immunohistochemistry with polyclonal antibody. Tiam1 expression in 9 human hepatoma cell lines, namely Huh-7, HepG2, Hep3B, SMMC-7721, QGy-7701, QGy-7703, BEL-7402, BEL-7404 and BEL-7405, and 1 normal primary human hepatocyte, HL-7702, was compared by means of fluorescence quantitative PCR, immunocytochemistry assay and Western blotting. We found that Tiam1 was significantly expressed in various malignancies. Tiam1 mRNA and protein levels were significantly elevated in the 9 human hepatoma cell lines compared to the normal primary human hepatocyte. Our results suggest that Tiam1 overexpression in malignant neoplasms could be a novel effective supplementary biomarker for tumors, including hepatocellular carcinoma. PMID- 21971870 TI - Molecular identification of a new begomovirus associated with yellow mosaic disease of Jatropha gossypifolia in India. AB - Yellow mosaic disease was observed on Jatropha gossypifolia plants growing in Kathaupahadi, Madhya Pradesh, India, and whiteflies (Bemisia tabaci) were found in the vicinity. Association of a new begomovirus with yellow mosaic disease of J. gossypifolia has been detected by PCR using begomovirus DNA-A-specific primers. The complete DNA-A genome (~2.7 kb) of this virus isolate was amplified by rolling-circle amplification (RCA) followed by digestion with Bam HI. The ~2.7 kb amplicons was cloned and sequenced, and the data obtained were submitted to GenBank under accession numbers FJ177030. The genome of the virus isolate consisted of six open reading frames (ORFs): V2 (pre-coat protein) and V1 (coat protein) in the virion sense and C3 (REn protein), C2 (TrAP protein), C1 (replication-associated protein) and C4 (C4 protein) in the complementary sense. BLASTn analysis of the nucleotide sequence (2757 nt) of the viral genome (FJ177030) showed 84-85% identity and a distinct phylogenetic relationship with DNA-A of tomato leaf curl virus-Bangalore II (U38239) and tomato leaf curl Karnataka virus (AY754812). Based on its 85% sequence identity to all other begomoviruses known to date and ICTV species demarcating criteria (< 88% identity), the name Jatropha yellow mosaic India virus (JYMIV) is proposed. JYMIV is considered to be monopartite, as neither DNA-B nor DNA-beta components associated with begomoviruses were detected. PMID- 21971871 TI - A member of the virus family Narnaviridae from the plant pathogenic oomycete Phytophthora infestans. AB - A virus that has properties consistent with inclusion in the virus family Narnaviridae was described in Phytophthora infestans, the oomycete that caused the Irish potato famine. The genome of phytophthora infestans RNA virus 4 (PiRV 4) is 2,984 nt with short complementary terminal sequences and a single open reading frame predicted to encode an RNA-dependent RNA polymerase (RdRp) most closely related to saccharomyces cerevisiae narnavirus 20S (ScNV-20S) and ScNV 23S, the members of the genus Narnavirus, family Narnaviridae. This report constitutes the first description of a member of the family Narnaviridae from a host taxon outside of the kingdom Fungi. PMID- 21971872 TI - Promising anticancer mono- and dinuclear ruthenium(III) dithiocarbamato complexes: systematic solution studies. AB - During the last decade, our research group has prepared a number of metal dithiocarbamato derivatives of Pt, Pd and Au that were expected to resemble the main features of cisplatin together with higher activity, improved selectivity and bioavailability, and lower side-effects. Furthermore, we have already published the synthesis, characterization and in vitro cytotoxicity studies of novel ruthenium(III) dithiocarbamato complexes such as [RuL(3)] monomers (11) and alpha-[Ru(2)L(5)]Cl dimers (12) with five different dithiocarbamate ligands. As both the monomer and the dinuclear complexes have shown significant antitumor activity in different human tumor cell lines, we decided to widen the characterization studies and to analyse thoroughly their behavior in physiological-like medium by UV-visible and CD spectroscopy. In the present paper we report on the crystal structure of [Ru(DMDT)(3)], [Ru(PDT)(3)] and [Ru(ESDT)(3)] complexes and we determine the spin state of the paramagnetic Ru(III) by means of Evans' method. Then, we discuss in detail the UV-visible spectral data of the complexes in different medium. All the studied complexes are stable in dimethyl sulfoxide, and show low solubility in phosphate buffered saline solution, particularly the monomer species, even at low concentration, while increased solubility for both types of complexes have been found in the presence of bovine serum albumin (BSA). Moreover, no changes on the coordination sphere of the metal, as well as no direct interaction between the BSA protein and the complex have been identified by UV-visible spectroscopy. However, some conformational changes on the BSA structure, induced by the ruthenium(III) complexes have been confirmed by CD spectroscopy, indicating a probable secondary electrostatic interaction between the metal complex and the peptide. In addition, no significant interaction has been demonstrated with the components of Dulbecco's Modified Eagle's Medium, used for the in vitro assays. PMID- 21971873 TI - The glucocorticoid stress response is repeatable between years in a wild teleost fish. AB - Patterns of glucocorticoid (GC) hormone regulation exhibit considerable inter individual variation that is often examined relative to individual traits and fitness measures. Although stress-induced GC concentrations are repeatable within an individual in captive populations, this assumption remains untested in wild animals in their natural environment across longer time periods. We assessed the repeatability of baseline and post-stress GC concentrations in a wild teleost fish. Largemouth bass (Micropterus salmoides) were captured and subjected to a standard stress protocol and then stocked into a small research lake. Upon recapture by angling up to 1 year later (n = 26), fish were re-sampled following identical methods. After controlling for a strong effect of water temperature, we confirmed repeatability of post-stress cortisol concentrations despite stress presumed to accompany relocation. We documented no consistency in baseline GC concentrations. This study serves as an important validation for the use of post stress cortisol concentrations as an individual trait. However, the effect size of repeatability was lower than that found in other taxa. Results also bring forth the reality that environmental variables such as temperature must be considered in studies where these factors can vary, such as when sampling wild animals at liberty. PMID- 21971874 TI - Validity, reliability and responsiveness of the EQ-5D in German stroke patients undergoing rehabilitation. AB - PURPOSE: To analyse the psychometric properties of the EQ-5D in German stroke survivors undergoing neurological rehabilitation. METHODS: The EQ-5D, the Hospital Anxiety and Depression Scale (HADS) and the Stroke Impact Scale (SIS) were completed before (210 subjects) and after (183 subjects) a patient education programme in seven rehabilitation clinics in Bavaria, Germany. A postal follow-up was conducted after 6 months. Acceptance, validity, reliability and responsiveness of the EQ-5D were tested. The SIS subscales were used as external anchors to classify the patients into change groups between the measurements. RESULTS: The proportion of missing answers ranged from 4.7 to 8.6%. Between 16 and 19% reported no problems in any EQ-5D dimension. At baseline, correlations between EQ-5D index and the SIS subscales ranged from 0.15 (communication) to 0.60 (mobility). Correlations with the EQ VAS were slightly smaller. All scores were reliable in test-retest with intraclass correlations ranging from 0.67 to 0.81. EQ-5D index and EQ VAS were consistently responsive only to improvements in health, showing small- to medium effect sizes (0.27-0.42). CONCLUSIONS: The EQ-5D has shown reasonable validity, reliability and, more limited, responsiveness in stroke patients with mild to moderate limitations of functional status, allowing it to be used in clinical trials in rehabilitation. PMID- 21971875 TI - PROMIS(r) Parent Proxy Report Scales: an item response theory analysis of the parent proxy report item banks. AB - OBJECTIVE: The objective of the present study is to describe the item response theory (IRT) analysis of the National Institutes of Health (NIH) Patient Reported Outcomes Measurement Information System (PROMIS((r))) pediatric parent proxy report item banks and the measurement properties of the new PROMIS((r)) Parent Proxy Report Scales for ages 8-17 years. METHODS: Parent proxy-report items were written to parallel the pediatric self-report items. Test forms containing the items were completed by 1,548 parent-child pairs. CCFA and IRT analyses of scale dimensionality and item local dependence, and IRT analyses of differential item functioning were conducted. RESULTS: Parent proxy-report item banks were developed and IRT parameters are provided. The recommended unidimensional short forms for the PROMIS((r)) Parent Proxy Report Scales are item sets that are subsets of the pediatric self-report short forms, setting aside items for which parent responses exhibit local dependence. Parent proxy-report demonstrated moderate to low agreement with pediatric self-report. CONCLUSIONS: The study provides initial calibrations of the PROMIS((r)) parent proxy-report item banks and the creation of the PROMIS((r)) Parent Proxy-Report Scales. It is anticipated that these new scales will have application for pediatric populations in which pediatric self-report is not feasible. PMID- 21971879 TI - Catalytic hydrofunctionalization of alkynes through P-H bond addition: the unique role of orientation and properties of the phosphorus group in the insertion step. AB - The puzzling question of alkyne insertion into Pd-P and Pd-H bonds leading to the formation of new Pd-C, C-P, and C-H bonds was explored by theoretical calculations at the CCSD(T) and B3LYP levels of theory. The key factors responsible for selectivity of catalytic hydrofunctionalization of alkynes were resolved and studied in details for the models of hydrophosphorylation, hydrophosphinylation, and hydrophospination reactions. In contrast with the generally accepted mechanistic picture, the calculations have shown that several pathways are possible depending on the nature and geometrical arrangement of the phosphorus group. It was found that the product of alkyne insertion into the metal-hydrogen bond should be easily formed under kinetic-control conditions, while the product of alkyne insertion into the metal-phosphorus bond may be formed in certain cases under thermodynamic control. For the first time, the calculations have revealed the role of the oxygen atom in the reactivity of P=P(O)R(2) groups and the role of the interactions involving the lone pair of the P=PR(2) group in the reagent. The fundamental properties of the Pd-P, C-P, and P H bonds were reported, and the larger bond strength upon increasing the number of oxygen atoms bound to phosphorus (P=PR(2), P(O)R(2), and P(O)(OR)(2)) have been shown. The relationship between bond energy, acidity, and reactivity of the studied phosphorus compounds has been determined. PMID- 21971878 TI - Improvement in reflux gastroesophagitis in a patient with spinal muscular atrophy after surgical correction of kyphoscoliosis: a case report. AB - BACKGROUND: Scoliosis, a three-dimensional deformity, has secondary effects on the gastrointestinal system. Reflux gastroesophagitis with hiatus hernia in patients with scoliosis is difficult to manage. We present a patient in whom primary correction of a spinal deformity was associated with resolution of symptoms of reflux. CASE DESCRIPTION: A 15-year-old girl with severe thoracolumbar kyphoscoliosis visited our scoliosis research institute complaining of back pain, positional imbalance, intermittent respiratory tract infections, and gastrointestinal discomfort such as pain, dysphagia, and heartburn for several years. On preoperative CT, her abdominal organs were in a deviant position, and esophagogastroduodenoscopy revealed severe reflux gastroesophagitis, Los Angeles classification (LA) Grade D, and a sliding hiatus hernia. After kyphoscoliosis correction, the patient's truncal balance and pain improved. Postoperatively, the patient reported abdominal pain and dysphagia that gradually subsided after 3 weeks. At 1 year, the patient had no abdominal complaints secondary to reflux gastroesophagitis, and episodes of recurrent respiratory tract infections were substantially reduced. Postoperative evaluation showed the reflux gastroesophagitis had improved to LA Grade A. Postoperative CT showed the abdominal cavity had expanded and the abdominal organs were more centered. LITERATURE REVIEW: The association between scoliosis and reflux gastroesophagitis is well documented. However, the secondary effects of scoliosis correction on gastrointestinal symptoms caused by reflux gastroesophagitis have not been investigated in detail. PURPOSE AND CLINICAL RELEVANCE: This patient illustrates the relationship between spinal deformity and gastrointestinal symptoms. Postural balance correction resulted in the alleviation of reflux gastroesophagitis symptoms secondary to hiatus hernia. PMID- 21971877 TI - A short tapered stem reduces intraoperative complications in primary total hip arthroplasty. AB - BACKGROUND: While short-stem design is not a new concept, interest has surged with increasing utilization of less invasive techniques. Short stems are easier to insert through small incisions. Reliable long-term results including functional improvement, pain relief, and implant survival have been reported with standard tapered stems, but will a short taper perform as well? QUESTIONS/PURPOSES: We compared short, flat-wedge, tapered, broach-only femoral stems to standard-length, double-tapered, ream and broach femoral stems in terms of intraoperative complications, short-term survivorship, and pain and function scores. PATIENTS AND METHODS: We retrospectively reviewed the records of 606 patients who had 658 THAs using a less invasive direct lateral approach from January 2006 to March 2008. Three hundred sixty patients (389 hips) had standard length stems and 246 (269 hips) had short stems. Age averaged 63 years, and body mass index averaged 30.7 kg/m(2). We recorded complications and pain and function scores and computed short-term survival. Minimum followup was 0.8 months (mean, 29.2 months; range, 0.8-62.2 months). RESULTS: We observed a higher rate of intraoperative complications with the standard-length stems (3.1%; three trochanteric avulsions, nine femoral fractures) compared with the shorter stems (0.4%; one femoral fracture) and managed all complications with application of one or more cerclage cables. There were no differences in implant survival, Harris hip score, and Lower Extremity Activity Scale score between groups. CONCLUSIONS: Fewer intraoperative complications occurred with the short stems, attesting to the easier insertion of these devices. While longer followup is required, our early results suggest shortened stems can be used with low complication rates and do not compromise the survival and functional outcome of cementless THA. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID- 21971880 TI - BSP-SLIM: a blind low-resolution ligand-protein docking approach using predicted protein structures. AB - We developed BSP-SLIM, a new method for ligand-protein blind docking using low resolution protein structures. For a given sequence, protein structures are first predicted by I-TASSER; putative ligand binding sites are transferred from holo template structures which are analogous to the I-TASSER models; ligand-protein docking conformations are then constructed by shape and chemical match of ligand with the negative image of binding pockets. BSP-SLIM was tested on 71 ligand protein complexes from the Astex diverse set where the protein structures were predicted by I-TASSER with an average RMSD 2.92 A on the binding residues. Using I-TASSER models, the median ligand RMSD of BSP-SLIM docking is 3.99 A which is 5.94 A lower than that by AutoDock; the median binding-site error by BSP-SLIM is 1.77 A which is 6.23 A lower than that by AutoDock and 3.43 A lower than that by LIGSITE(CSC) . Compared to the models using crystal protein structures, the median ligand RMSD by BSP-SLIM using I-TASSER models increases by 0.87 A, while that by AutoDock increases by 8.41 A; the median binding-site error by BSP-SLIM increase by 0.69A while that by AutoDock and LIGSITE(CSC) increases by 7.31 A and 1.41 A, respectively. As case studies, BSP-SLIM was used in virtual screening for six target proteins, which prioritized actives of 25% and 50% in the top 9.2% and 17% of the library on average, respectively. These results demonstrate the usefulness of the template-based coarse-grained algorithms in the low-resolution ligand-protein docking and drug-screening. An on-line BSP-SLIM server is freely available at http://zhanglab.ccmb.med.umich.edu/BSP-SLIM. PMID- 21971881 TI - Synthesis of highly stable fluorescent Ag nanocluster @ polymer nanoparticles in aqueous solution. AB - Water-soluble, highly stable fluorescent Ag nanoclusters have been synthesized using a novel core/shell solid polymer (PMMA/PMMA-PMAA) nanoparticles as a novel template. The photoluminescence, ultraviolet-visible absorption, X-ray photoelectron (XPS), laser desorption time of flight mass spectroscopies (LDI-ToF MS) and transmission electron microscopy (TEM) were carried out to characterize the optical properties and morphologies of Ag nanoclusters. The quantum yield of Ag nanoclusters reached 6% and the lifetime of Ag nanoclusters was 0.460 ns. Because of the protective structure of three-dimensional network of the polymer template, the Ag nanoclusters have high stability. And this highly stable fluorescent Ag nanoclusters have successfully been applied for bioimaging. PMID- 21971882 TI - Minimum savings requirements in shared savings provider payment. AB - Payer (insurer) sharing of savings is a way of motivating providers of medical services to reduce cost growth. A Medicare shared savings program is established for accountable care organizations in the 2010 Patient Protection and Affordable Care Act. However, savings created by providers cannot be distinguished from the normal (random) variation in medical claims costs, setting up a classic principal agent problem. To lessen the likelihood of paying undeserved bonuses, payers may pay bonuses only if observed savings exceed minimum levels. We study the trade off between two types of errors in setting minimum savings requirements: paying bonuses when providers do not create savings and not paying bonuses when providers create savings. PMID- 21971883 TI - Functional importance of the internal anal sphincter in fistula surgery: correspondence for the original article entitled "For many high anal fistulas, lay open is still a good option" by GK Atkin, J Martins, P Tozer, P Ranchod, RKS Phillips (2011) Tech Coloproctol 15:143-150. PMID- 21971884 TI - [38-year-old patient with weight loss and night sweat. Hairy cell leukemia]. PMID- 21971885 TI - [Diagnostic imaging in patients with coronary artery disease: the nuclear medicine physicians' view]. AB - Actually myocardial perfusion scintigraphy (MIP) is best evaluated imaging modality in patients with coronary artery disease. It detects flow-limiting coronary artery disease with high sensitivity and specificity, enables recognition of the grade of severity and extensiveness of myocardial ischemia, and furthermore enables assessment of future cardiac events independently of clinical and diagnostic parameters. Due to rapid technical evolution in diagnostic tools there is need of comparison between MIP and other concurrent imaging modalities such as stress echocardiography, Cardio-CT and Cardio-MRI in patients with coronary artery disease. PMID- 21971886 TI - [Environmental Chlamydiae with medical significance]. AB - The molecular biological analysis of a chlamydia-like bacterium from Acanthamoeba sp., originated from the nasal mucosa of a female subject, led to the description of the new species Parachlamydia acanthamoebae. It provided the basis for establishing its own family Parachlamydiaceae, which was genetically separated from the traditional Chlamydiaceae. In the following years other chlamydia-like bacteria, replicating within different free-living amoeba species, have been observed. Due to their close genetic distance to P. acanthamoebae, they have been classified as Parachlamydiaceae. Thus, the description of the two novel genera, Neochlamydia and Metachlamydia, as well as a new species, Protochlamydia naegleriophila, was accomplished. Their role as potential pathogens was confirmed in a number of cases by antibodies and DNA detection in patient material. PMID- 21971887 TI - [Surgical replacement or transcatheter implantation?: how decisions should be made in aortic stenosis]. PMID- 21971888 TI - [Inflammation of the jaws during treatment with bisphosphonates]. PMID- 21971890 TI - A phase II study of insulin-like growth factor receptor inhibition with nordihydroguaiaretic acid in men with non-metastatic hormone-sensitive prostate cancer. AB - Insulin-like growth factor (IGF)-mediated signaling is a newly recognized clinical target in prostate cancer, and it is hypothesized that blockade of the IGF receptor (IGF1R) will impair downstream signaling and slow tumor growth. In this study the efficacy of nordihydroguaiaretic acid (NDGA), a small molecule inhibitor of the IGF-1R, was prospectively evaluated in patients with non metastatic hormone-sensitive prostate cancer (HSPC). Eligible patients had non metastatic HSPC with a rising prostate-specific antigen (PSA) and a normal testosterone level. NDGA 2000 mg was given orally daily in 28 day cycles and treatment continued until PSA progression or toxicity. Accrual was stopped early after a pre-planned interim analysis showed no significant PSA declines after 3 cycles of treatment among the first 12 patients enrolled. Median time on treatment was 9 cycles (range 2-19) for 11 patients now off study; 1 patient continues to receive therapy and has been on study for 29 months. Seven patients experienced non-sustained declines in PSA ranging from 1.9 to 15.8% of baseline. PSADT lengthened by a median of 1.4 months for all evaluable patients when compared to pretreatment PSADT (range -6.1 to +19.8 months). Grade 3 events were rare and included nausea/vomiting, syncope due to dehydration, and elevated liver function tests in 1 patient, and cognitive disturbance in another patient. NDGA therapy lengthens median PSADT but does not induce significant PSA declines. Further study may require a placebo-control to determine if changes in PSADT are drug related. PMID- 21971889 TI - Inhibitor of growth-4 mediates chromatin modification and has a suppressive effect on tumorigenesis and innate immunity. AB - Inhibitor of growth-4 (ING4) is a member of the ING family and acts as a tumor suppressor protein. ING4 is a promising candidate for cancer research due to its anti-angiogenic function and its role in the inhibition of cell migration, cell cycle, and induction of apoptosis. Interaction of this protein with the histone acetyl transferase complex plays a vital role in the regulation of multiple nuclear factor kappa light chain enhancer of activated B cells response elements and thus in the regulation of innate immunity. Splice variants of ING4 have different binding affinities to target sites, which results in the enhancement of its functional diversity. ING4 is among the few known regulatory proteins that can directly interact with chromatin as well as with transcription factors. The influence of ING4 on tumor necrosis factor-alpha, keratinocyte chemoattractant, interleukin (IL)-6, IL-8, matrix metalloproteinases, cyclooxygenase-2, and IkappaBalpha expression clearly demonstrates its critical role in the regulation of inflammatory mediators. Its interaction with liprin alpha1 and p53 contribute to mitigate cell spreading and induce apoptosis of cancer cells. Multiple factors including breast cancer melanoma suppressor-1 are upstream regulators of ING4 and are frequently deactivated in tumor cells. In the present review, the different properties of ING4 are discussed, and its activities are correlated with different aspects of cell physiology. Special emphasis is placed on our current understanding of ING4 with respect to its influence on chromatin modification, tumorigenesis, and innate immunity. PMID- 21971891 TI - Construction of a high density integrated genetic map for cucumber (Cucumis sativus L.). AB - The high-density consensus map was constructed based on the GY14 * PI 183967 map from an inter-subspecific cross and the extended S94 * S06 map from an intra subspecific cross. The consensus map was composed of 1,369 loci, including 1,152 SSR loci, 192 SRAP loci, 21 SCAR loci and one STS locus as well as three gene loci of fruit external quality traits in seven chromosomes, and spanned 700.5 cM, of which 682.7 cM (97.5%) were covered by SSR markers. The average genetic distance and physical interval between loci were 0.51 cM and ~268 kbp, respectively. Additionally, the physical position of the sequence-associated markers aligned along the assembled cucumber genome sequence established a relationship between genetic maps and cucumber genome sequence and to a great extent validated the order of markers in individual maps and consensus map. This consensus map with a high marker density and well-ordered markers is a saturated and reliable linkage map for genetic analysis of cucumber or the Cucurbitaceae family of plants. PMID- 21971892 TI - Association of dilated retinal arteriolar caliber with early age-related macular degeneration: the Handan Eye Study. AB - BACKGROUND: To identify factors associated with early age-related macular degeneration (AMD) in a rural Chinese population, with emphasis on retinal vessel caliber. METHODS: The study population comprised the 6,830 participants of the Handan Eye Study. All participants underwent digital retinal photography of both eyes. Trained graders assessed the presence of AMD lesions. Arteriolar and venular diameters were measured with a specific computer-assisted program and were summarized as the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE). RESULTS: The data for the 199 individuals with evaluable retinal photographs and early AMD and 400 age-matched individuals randomly selected from the group without AMD were analyzed. After adjusting for participants' age, sex, smoking status, hypertension, diabetes, BMI, and CRVE, the multivariate adjusted model showed that a higher CRAE was significantly associated with early AMD (OR = 1.34; 95% CI: 1.05-1.71; p = 0.020) and the presence of soft distinct drusen (OR = 1.32 (95% CI: 1.02-1.71, p = 0.037). There were no significant associations between CRVE and early AMD. CONCLUSIONS: Dilated retinal arteriolar caliber is associated with early AMD and soft distinct drusen in this population. We found no significant associations between CRAE and other characteristics of the retina related to AMD or between retinal venal caliber and early AMD. More research is needed to determine whether the difference between these results and those previously published stem from the rural living conditions of the participants or other factors. PMID- 21971893 TI - Healthcare systems: what do we want? PMID- 21971894 TI - Health technology assessment in Brazil: what do healthcare system players think about it? AB - CONTEXT AND OBJECTIVES: The health technology assessment (HTA) process has been developed locally. The aim of this study was to describe, analyze and compare the opinions of participants in international health economics symposia about the HTA process used in Brazil. DESIGN AND SETTING: Observational cross-sectional study at the 2006 and 2008 International Health Economics Symposia, in Sao Paulo. METHODS: A structured questionnaire was applied. For the statistical analysis, the percentage distribution for each category was calculated, and variables were compared using tests for two-sample proportion hypotheses. RESULTS: Totals of 153 and 74 participants answered the 2006 and 2008 surveys, respectively. The response rate was better for the 2006 survey (67.1%) than for the 2008 survey (31.8%). Most interviewees were between the ages of 30 and 49 years and were managers in the healthcare system. Most of them considered that the current HTA process was incomplete and unable to meet the needs of the healthcare system. They mentioned the government, academia and experts as the three main groups of people who should be involved in the process, and selected efficiency/effectiveness, safety and disease relevance as the three main criteria to be considered in the HTA process. There is a trend towards developing decentralized regionalized HTA processes, with separate assessment and decision making for the public and private systems. CONCLUSIONS: The HTA concept is well known. Healthcare system players feel that the process has methodological limitations. Additional surveys are needed to track the HTA process and its application in Brazil. PMID- 21971895 TI - Effects of transcutaneous electrical nerve stimulation (TENS) and interferential currents (IFC) in patients with nonspecific chronic low back pain: randomized clinical trial. AB - CONTEXT AND OBJECTIVE: Transcutaneous electrical nerve stimulation (TENS) and interferential current are the most used electrotherapy methods, although there is little scientific evidence to support their use. The aim of this study was to compare the effects of TENS and interferential current among patients with nonspecific chronic low back pain. DESIGN AND SETTING: Single-blind randomized controlled trial in the Department of Physiotherapy, Centro Universitario de Maringa. METHODS: One hundred and fifty patients were randomly divided into three groups: TENS (group 1), interferential current (group 2) and controls (group 3). The patients designated for electrotherapy received ten 30-minute sessions, while the control group remained untreated. All patients and controls were evaluated before and after treatment using a visual analog scale and the McGill Pain and Roland Morris questionnaires, and regarding their use of additional medications. RESULTS: There was a mean reduction on the visual analog scale of 39.18 mm with TENS, 44.86 mm with interferential current and 8.53 mm among the controls. In the Roland Morris questionnaire, group 1 had a mean reduction of 6.59; group 2, 7.20; and group 3, 0.70 points. In group 1, 84% of the patients stopped using medications after the treatment; in group 2, 75%; and in group 3, 34%. There was no statistically significant difference between the TENS and interferential current groups (P > 0.05); a difference was only found between these groups and the controls (P < 0.0001). CONCLUSION: There was no difference between TENS and interferential current for chronic low back pain treatment. CLINICAL TRIAL REGISTRATION: NCT01017913. PMID- 21971896 TI - Steatosis of indeterminate cause in a pediatric group: is it a primary mitochondrial hepatopathy? AB - CONTEXT AND OBJECTIVE: In children, hepatic steatosis may be related to inborn errors of metabolism (IEMs) or to non-alcoholic fatty liver disease (NAFLD). The aim of this study was to assess and characterize steatosis of indeterminate cause through morphological and morphometric analysis of liver tissue. DESIGN AND SETTING: Cross-sectional study at the Departments of Pathology of Faculdade de Ciencias Medicas, Universidade Estadual de Campinas (FCM-Unicamp) and Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (FMB-Unesp). METHODS: Eighteen consecutive liver biopsies obtained from 16 patients of ages ranging from 3 months to 12 years and nine months that were inserted in a database in the study period were analyzed using optical microscopy and transmission electron microscopy. Through electron microscopy, the mitochondrial density and mean mitochondrial surface area were determined in hepatocytes. Ten patients ranging in age from 1 to 14 years were used as a control group. RESULTS: "Pure" steatosis was detected, unaccompanied by fibrosis or any other histological alteration. Microvesicular steatosis predominated, with a significant increase in mean mitochondrial surface area. CONCLUSION: Microvesicular steatosis may be related to primary mitochondrial hepatopathy, especially due to reduction of beta oxidation or partial stagnation of oxidative phosphorylation. For these reasons, this form of steatosis (which should not be called "pure") is likely to represent an initial stage in the broad spectrum of NAFLD. We have drawn attention to cases of steatosis in the pediatric group, in which the microvesicular form predominates, since this may be associated with mitochondrial disorders. PMID- 21971897 TI - Patient perceptions about anesthesia and anesthesiologists before and after surgical procedures. AB - CONTEXT AND OBJECTIVE: Anesthesiologist-patient relationships are established preoperatively and intraoperatively. These are opportunities for providing correct information about anesthesia/anesthesiologists, thereby improving outcomes. The aim here was to evaluate patients' perceptions about anesthesiologists before anesthesia and to identify whether the anesthetic care would change such perceptions. DESIGN AND SETTING: Prospective cross-sectional study using data obtained in 2007-2008, at a tertiary university hospital. METHODS: 518 patients aged 16 years or over were interviewed before and after anesthesia exposure. A questionnaire was used to determine patient characteristics and perceptions of anesthesia/anesthesiologists. RESULTS: The patients were 16-89 years of age and 59.8% had attended elementary school. 79.1% said that anesthesiologists were specialized physicians. Anesthesiologists' roles were associated with loss of consciousness (35.5% pre-anesthesia; 43.5% post anesthesia), pain relief (29.7% pre-anesthesia, 31.7% post-anesthesia), vital sign monitoring (17.6% pre-anesthesia, 35% post-anesthesia; P < 0.05); and drug administration (10.8% pre-anesthesia, 43.9% post-anesthesia; P < 0.05). The level of confidence in the physician was rated high (82.2% and 89.8% pre- and post anesthesia, respectively; P < 0.05) or intermediate (5.8% and 6.6% pre- and post anesthesia, respectively; P < 0.05). The care provided by anesthesiologists was classified as: elucidating (52.8%), encouraging (52.6%), neutral (10.2%) and careless (0.8%). CONCLUSION: Patients' perceptions of anesthesiologists' roles were fairly good, but improvements in this relationship still need to be pursued, to achieve better outcomes. Anesthetic care was important in providing information, confidence and reassurance among patients, regarding their perceptions. Anesthesiologists should not miss opportunities to provide excellent professional care for patients, thereby improving anesthesia outcomes and their image. PMID- 21971898 TI - Functional assessment of cancer therapy-brain questionnaire: translation and linguistic adaptation to Brazilian Portuguese. AB - CONTEXT AND OBJECTIVE: Quality of life assessment among patients with brain tumors is important, given that new treatments have increased patient survival. The aim of this study was to translate the Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire (version 4) into Portuguese, carry out cross-cultural adaptation and assess its reproducibility. DESIGN AND SETTING: Cohort at the Universidade Federal de Sao Paulo (Unifesp). METHODS: Forty patients with a brain tumor seen at the neuro-oncology outpatient clinic participated in the study. The process of translation and back-translation was carried out, along with adaptation to the Portuguese language and Brazilian culture. The intraclass correlation coefficient (ICC) was used to test the reproducibility of the FACT-Br (version 4). RESULTS: The reproducibility of the questionnaire was excellent (ICC = 0.95; 95% confidence interval, CI: 0.89-0.97). The ICC with a mean interval of 15 days between applications of the questionnaire was very good in all domains (ICC = 0.87 to 0.95). The mean time taken to answer the questionnaire was 6.27 +/- 2.26 minutes, ranging from 3 to 11 minutes. CONCLUSION: The translated version of the FACT-Br questionnaire (version 4) adapted to the Portuguese language and Brazilian culture proved to be easily understood and achieved very good reproducibility among patients with diagnoses of brain tumors. PMID- 21971899 TI - Estrogen and progesterone receptor testing in breast carcinoma: concordance of results between local and reference laboratories in Brazil. AB - CONTEXT AND OBJECTIVE: Breast cancer accounts for approximately one quarter of all cancers in females. Estrogen and progesterone receptor testing has become an essential part of the clinical evaluation of breast carcinoma patients, and accurate results are critical in identifying patients who may benefit from hormone therapy. The present study had the aim of investigating the concordance of the results from hormone receptor tests between a reference laboratory and local (or community) laboratories in Brazil. DESIGN AND SETTING: Retrospective study at a reference pathology laboratory. METHODS: The concordance in the results from hormone receptor tests between a reference laboratory and 146 local laboratories in Brazil was compared in relation to 500 invasive breast carcinoma cases, using immunohistochemistry. RESULTS: There was concordance in 89.4% (447/500 cases) and 85.0% (425/500 cases) of the results from estrogen (kappa = 0.744, P < 0.001) and progesterone (kappa = 0.688, P < 0.001) receptor tests, respectively, between local and reference laboratories. This was similar to findings in other countries. The false negative rates from estrogen and progesterone receptor tests in local laboratories were 8.7% and 14.4%, respectively. The false positive rates from estrogen and progesterone receptor tests in local laboratories were 15.5% and 16.0%, respectively. CONCLUSION: Technical and result interpretation issues may explain most of the discordances in hormone receptor testing in local laboratories. Validation of estrogen and progesterone receptor tests at local laboratories, with rigorous quality control measures, is strongly recommended in order to avoid erroneous treatment of breast cancer patients. PMID- 21971900 TI - Bronchial provocation tests in clinical practice. AB - Bronchial hyperresponsiveness, which consists of an exaggerated response of the airways to bronchoconstrictor stimuli, is one of the main characteristics of asthma, presented in nearly all asthmatic patients. Bronchial hyperresponsiveness may also be present in other diseases, such as allergic rhinitis, chronic obstructive pulmonary disease, cystic fibrosis, heart failure and respiratory infection, and with some medications, such as beta-blockers. Bronchial provocation tests (also known as bronchial challenges) are used to evaluate bronchial responsiveness. These tests have become increasingly used over the last 20 years, with the development and validation of accurate, safe and reproducible tests, and with the publication of well-detailed protocols. Several stimuli can be used in a bronchial challenge, and they are classified as direct and indirect stimuli. There are many indications for a bronchial challenge. In this review, we discuss the main differences between direct and indirect stimuli, and the use of bronchial challenges in clinical practice, especially for confirming diagnoses of asthma, exercise-induced bronchoconstriction and cough-variant asthma, and for use among elite-level athletes. PMID- 21971901 TI - Comparative evaluation of digital mammography and film mammography: systematic review and meta-analysis. AB - CONTEXT AND OBJECTIVE: Mammography is the best method for breast-cancer screening and is capable of reducing mortality rates. Studies that have assessed the clinical impact of mammography have been carried out using film mammography. Digital mammography has been proposed as a substitute for film mammography given the benefits inherent to digital technology. The aim of this study was to compare the performance of digital and film mammography. DESIGN: Systematic review and meta-analysis. METHOD: The Medline, Scopus, Embase and Lilacs databases were searched looking for paired studies, cohorts and randomized controlled trials published up to 2009 that compared the performance of digital and film mammography, with regard to cancer detection, recall rates and tumor characteristics. The reference lists of included studies were checked for any relevant citations. RESULTS: A total of 11 studies involving 190,322 digital and 638,348 film mammography images were included. The cancer detection rates were significantly higher for digital mammography than for film mammography (risk relative, RR = 1.17; 95% confidence interval, CI = 1.06-1.29; I2 = 19%). The advantage of digital mammography seemed greatest among patients between 50 and 60 years of age. There were no significant differences between the two methods regarding patient recall rates or the characteristics of the tumors detected. CONCLUSION: The cancer detection rates using digital mammography are slightly higher than the rates using film mammography. There are no significant differences in recall rates between film and digital mammography. The characteristics of the tumors are similar in patients undergoing the two methods. PMID- 21971902 TI - Anti-Toxoplasma gondii antibodies in pregnant women and their newborn infants in the region of Sao Jose do Rio Preto, Sao Paulo, Brazil. AB - CONTEXT AND OBJECTIVE: Toxoplasmosis transmission during pregnancy can cause severe sequelae in fetuses and newborns. Maternal antibodies may be indicators of risk or immunity. The aim here was to evaluate seropositivity for anti-Toxoplasma gondii (anti-T. gondii) immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies and IgG avidity in pregnant women and their newborn infants. DESIGN AND SETTING: Cross-sectional study in a high-risk pregnancy outpatient clinic. METHODS: Serum samples from pregnant women (n = 87) and their respective newborns (n = 87) were evaluated for anti-T. gondii antibodies using indirect immunofluorescence (IIF) (IgM and IgG), enzyme-linked immunosorbent assay (ELISA) (IgG) and an avidity test. RESULTS: Anti-T. gondii antibodies were identified in 64.4% of the serum samples from the mothers and their infants (56/87). Except for two maternal serum samples (2.3%), all others were negative for anti-T. gondii IgM antibodies, using IIF. The results showed that 92.9% of the pregnant women had high IgG avidity indexes (> 30%) and four samples had avidity indexes between 16 and 30%. Two women in the third trimester of pregnancy were positive for anti T. gondii IgM antibodies; their babies had avidity indexes between 16 and 30%. The avidity indexes of serum from the other 83 newborns were similar to the results from their mothers. CONCLUSIONS: The results showed that 2% of the pregnant women were at risk of T. gondii transmission during the gestational period. These data seem to reflect the real situation of gestational toxoplasmosis in the northwestern region of the state of Sao Paulo. PMID- 21971903 TI - Sydenham's chorea in a family with Huntington's disease: case report and review of the literature. AB - CONTEXT: Sydenham's chorea affects almost 30% of patients with acute rheumatic fever. It is more frequent in females and is rare in the first decade of life, and genetic vulnerability underlies it. Because of easy access to antibiotics, it is now rare in so-called developed countries. CASE REPORT: A 6-year-old boy with a family history of Huntington's disease, who was the only child of an unscreened and asymptomatic mother, was brought for a consultation because of migratory arthralgia, depressed mood, and rapid, abrupt and unintentional movements of his right arm and leg, that had evolved over a three-week period. On physical examination, he presented a grade III/VI systolic heart murmur and right-side choreic movements, giving rise to a deficit of active mobilization. Laboratory tests revealed elevated erythrocyte sedimentation rate (63 mm/h), C-reactive protein (25 mg/l) and antistreptolysin O titer (1,824 U/ml). Cardiovascular evaluation showed mild aortic insufficiency, moderate mitral insufficiency and a prolonged PR interval. A clinical diagnosis of Sydenham's chorea/acute rheumatic fever was made, and therapy consisting of penicillin, haloperidol, captopril and furosemide was instituted, with excellent results. CONCLUSION: In developed countries, Sydenham's chorea seems forgotten and, because of this, little is known about its clinical course and controversy surrounds the therapeutic options available. This occurrence of rheumatic chorea in a family with Huntington's disease highlights the importance of the differential diagnosis for the different forms of chorea. PMID- 21971904 TI - Two consecutive intrauterine pregnancies following transperitoneal ovum migration. AB - CONTEXT: Transperitoneal migration is a mechanism for oocyte retrieval that is generally demonstrated in certain cases of ectopic pregnancy. However, the association between these two conditions is debatable. The rare occasions on which intrauterine pregnancy following transperitoneal migration can be documented are an opportunity for studying this topic. CASE REPORT: We report the case of a female with a history of salpingectomy due to an ectopic pregnancy at 31 years of age. Two subsequent pregnancies were intrauterine. In both of them, ultrasound revealed that the corpus luteum was located in the ovary ipsilateral to the salpingectomy. CONCLUSION: To our knowledge, this is the first reported case of two intrauterine pregnancies following transperitoneal migration, carried to term, and resulting in the delivery of two healthy children. The clinical and physiological implications are discussed. PMID- 21971907 TI - Delayed recovery of paraplegia following surgical evacuation of spontaneous cervicothoracic epidural hematoma. PMID- 21971908 TI - Genetic-environmental interaction in a unique case of Muenke syndrome with intracranial hypertension. PMID- 21971909 TI - Antinociceptive effect of intrathecal administration of hypotaurine in rat models of inflammatory and neuropathic pain. AB - Hypotaurine is an intermediate in taurine biosynthesis from cysteine in astrocytes. Although hypotaurine functions as an antioxidant and organic osmolyte, its physiological role in the central nervous system remains unclear. This study used behavioral assessments to determine whether hypotaurine influenced nociceptive transmission in acute, inflammatory, and neuropathic pain. The tail flick, paw pressure, and formalin tests were performed in male Sprague Dawley rats to examine the effects of the intrathecal administration of hypotaurine (100, 200, 400, 600 MUg) on thermal, mechanical, and chemical nociception. Chronic constriction injury (CCI) to the sciatic nerve was induced in the rats, and the electronic von Frey test and plantar test were performed to assess the effects on neuropathic pain. To determine which neurotransmitter pathway(s) was involved in the action of hypotaurine, in this study, we examined how the antagonists of spinal pain processing receptors altered the effect of 600 MUg hypotaurine. To explore whether hypotaurine affected motor performance, the Rotarod test was conducted. Hypotaurine had antinociceptive effects on thermal, mechanical, and chemical nociception in the spinal cord. In CCI rats, hypotaurine alleviated mechanical allodynia and thermal hyperalgesia. These effects were reversed completely by pretreatment with an intrathecal injection of strychnine, a glycine receptor antagonist. Conversely, hypotaurine did not affect motor performance. This study demonstrated that intrathecal hypotaurine suppressed acute, inflammatory, and neuropathic pain. Hypotaurine may regulate nociceptive transmission physiologically by activating glycinergic neurons in the spinal cord, and it is a promising candidate for treating various pain states. PMID- 21971910 TI - Anti-C1q antibodies as a diagnostic marker of proliferative lupus nephritis: comment on the article by Katsumata et al. PMID- 21971911 TI - The effect of diet and feeding level on survival and weight gain of hand-raised harbor seal pups (Phoca vitulina). AB - Hundreds of stranded harbor seals pups (Phoca vitulina) are brought to wildlife rescue centers every year. Typical hand-rearing diets include artificial milk replacers and diets based on macerated fish fed via gavage, but weight gains are often low and mortality rates can be high. This study compared survival and weight gain of orphaned seal pups fed either artificial milk-replacer or fish formula. Pups admitted to the facility in summer 2007 (n=145) and 2008 (n=98) were randomly assigned to one of two diets and fed by gavage until weaning. In 2007, pups fed milk-replacer gained more (43 +/- 12 g/d) than those fed fish formula (loss of 13 +/- 6 g/d; P<0.002). In 2008, when intake was increased from 8 to 11% of body weight daily, weight gain improved for both diets but remained higher in pups fed milk-replacer (123 +/- 12 g/d, vs. loss of 6 +/- 8 g/day; P<0.001). Pup survival to weaning was significantly higher in 2008 than 2007 (P<0.001) and was higher for pups on milk-replacer compared with those on fish formula (P<0.05). Survival was also correlated with body weight at admittance (P<0.001). Although neither diet achieved the weight gains recorded in mother raised pups (400-800 g/d), the artificial milk-replacer was clearly more successful, and pups fared better in the second year of the study when intake was higher. PMID- 21971912 TI - Electrocardiogram analysis of the normal unanesthetized green peafowl (Pavo muticus). AB - The aim of this study was to describe normal electrocardiogram (ECG) patterns and values in unanesthetized green peafowl (Pavo muticus). The standard bipolar and augmented unipolar limb leads ECGs were recorded in the birds. The waveforms were analyzed in all leads at 50 mm/sec and at 10 mm = 1 mV to determine P, PR (segment and interval), QRS, ST, QT durations, P, net QRS complex and T amplitudes. The polarity of each waveform was tabulated in all leads. The mean electrical axis (MEA) for the frontal plane was calculated using leads II and III. The mean heart rates were calculated from lead II that was 257.5 +/- 5.33 beats/min. The P wave was dominantly positive in all leads. The dominant pattern of waveforms of the QRS complexes were QS in leads II, III, and aVF. In leads I, aVR and aVL, the R pattern was dominant. The T wave was almost positive in leads I, II, and aVF. The average value of the heart MEA was -96.75 +/- 3.31 degrees . Description of normal ECG parameters will facilitate a better realizing of ECG changes of unhealthy green peafowls. PMID- 21971913 TI - Estimating daily walking distance of captive African elephants using an accelerometer. AB - Two central concerns for elephant husbandry and management are whether zoological enclosures are appropriately sized and the degree to which naturalistic exercise and activity are observed in such enclosures. In order to address these issues, accurate data on the daily walking distance of elephants both in situ and ex situ are necessary. We used an accelerometer, a pedometer that measures step count and activity level, to estimate walking distance in African elephants (Loxodonta africana) at the San Diego Zoo's Wild Animal Park. The accelerometer was worn simultaneously with a GPS unit that recorded actual walking distance. Estimates of walking distance were extrapolated from the accelerometer and compared with actual distances determined by GPS data. The accelerometer was found to overestimate step count, and subsequently walking distance, by including false counts of steps. Extrapolating walking distance based upon stride length measurements did not match actual GPS walking distance. However, activity level output from the accelerometer significantly correlated with actual GPS walking distance. In addition, we report that the rate of movement is comparable to that reported in other zoological settings. We provide a linear regression equation that can be utilized by other institutions to estimate daily walking distance of elephants in their collection who are outfitted with accelerometers. PMID- 21971914 TI - Establishment and characterization of human non-small cell lung cancer cell lines. AB - Non-small cell lung cancer (NSCLC), a highly malignant tumor, is common in China and is associated with a very poor 5-year survival rate. To better understand the cancer biology of this disease, we report here the establishment of three new NSCLC cell lines, SCC210011, SCC211441 and ACC212102, from the tumor tissue of three NSCLC patients. By histological analysis, we found that all three cell lines displayed the typical features of endothelial cancer cells. The population doubling times of SCC210011, SCC211441 and ACC212102 cells were 42, 38 and 25 h, respectively. Our cytogenetic studies indicated that these cell lines exhibit structural and numerical chromosomal abnormalities. Furthermore, the tumorigenicity in nude mice was confirmed, and H&E staining results revealed that they resembled the primary tissue. These newly established cell lines may serve as useful models for studying the molecular pathogenesis of NSCLC. PMID- 21971915 TI - The role of glutamate transporter-1a in the induction of brain ischemic tolerance in rats. AB - This study was undertaken to determine the role of glutamate transporter-1a (GLT 1a), one of the splice variants of glutamate transporter-1, in the induction of brain ischemic tolerance by cerebral ischemic preconditioning (CIP). We used a rat global cerebral ischemic model and assessed changes by neuropathological evaluation, Western blot analysis, immunohistochemistry, real-time PCR, in vivo brain microdialysis, and high performance liquid chromatography. We found that CIP induced a significant upregulation of GLT-1a expression in the CA1 hippocampus in a time course corresponding to that of neuroprotection of CIP against brain ischemia. Severe brain ischemia for 8 min induced delayed downregulation of GLT-1a, an obvious increase in glutamate concentration and delayed neuronal death of the pyramidal neurons in the CA1 hippocampus. When the animals were pretreated with CIP before the severe ischemia, the above changes normally induced by the severe ischemia were effectively prevented. Importantly, such a preventive effect of CIP on these changes was significantly inhibited by intracerebroventricular administration of GLT-1a antisense oligodeoxynucleotides, which have been proven to specifically inhibit the expression of GLT-1a protein and mRNA, and had no effect on the expression of GLT-1b. In addition, the concentration of aspartate was also elevated after severe brain ischemic insult. However, CIP had no effect on the elevated aspartate concentrations. These results indicate that GLT-1a participated in the brain ischemic tolerance induced by CIP in rats. PMID- 21971917 TI - A base-free thorium-terminal-imido metallocene: synthesis, structure, and reactivity. AB - The synthesis, structure, and reactivity of a base-free thorium terminal-imido metallocene have been comprehensively studied. Treatment of thorium metallocenes [{eta(5)-1,2,4-(Me(3)C)(3)C(5)H(2)}(2)ThMe(2)] and [{eta(5)-1,3 (Me(3)C)(2)C(5)H(3)}(2)ThMe(2)] with RNH(2) gives diamides [{eta(5)-1,2,4 (Me(3)C)(3)C(5)H(2)}(2)Th(NHR)(2)] (R=Me (7), p-tolyl (8)) and [{eta(5)-1,3 (Me(3)C)(2)C(5)H(3)}(2)Th(NH-p-tolyl)(2)] (9), respectively. Diamides 7 and 9 do not eliminate methylamine or p-toluidine, but sublime without decomposition at 150 degrees C under vacuum (0.01 mmHg), whereas diamide 8 is converted at 140 degrees C/0.01 mmHg into the primary amine p-tolyl-NH(2) and [{eta(5)-1,2,4 (Me(3)C)(3)C(5)H(2)}(2)Th=N(p-tolyl)] (10), which may be isolated in pure form. Imido metallocene 10 does not react with electrophiles such as alkylsilyl halides; however, it reacts with electron-rich or unsaturated reagents. For example, reaction of 10 with sulfur affords the metallacycle [{eta(5)-1,2,4 (Me(3)C)(3)C(5)H(2)}(2)Th{N(p-tolyl)S-S}]. Imido 10 is an important intermediate in the catalytic hydroamination of internal alkynes, and an efficient catalyst for the trimerization of PhCN. Density functional theory (DFT) studies provide a detailed understanding of the experimentally observed reactivity patterns. PMID- 21971916 TI - Epigenetic modulation of human breast cancer by metallofullerenol nanoparticles: in vivo treatment and in vitro analysis. AB - Multi-hydroxylated endohedral metallofullerenol [Gd@C(82)(OH)(22)](n) nanoparticles possess the general physico-chemical characteristics of most nanoparticles. They also exhibit uniquely low toxicity and antineoplastic efficacy. In the current study, the molecular mechanisms and epigenetic characteristics of the antineoplastic action of these nanoparticles are explored. Human breast cancer MCF-7 and human umbilical vein endothelial ECV304 cell lines were used. Cell viability assay, cell hierarchical cluster analysis by cDNA microarray, semi-quantitative reverse transcription-polymerase chain reaction and Western blot analysis were conducted to investigate the changes in molecular and cellular signaling pathways caused by [Gd@C(82)(OH)(22)](n). The results demonstrated the high antitumor activity and low cytotoxicity of [Gd@C(82)(OH)(22)](n) nanoparticles both in vivo and in vitro. Their possible anti-tumor mechanisms were also discussed. The present study may provide new insight into the mechanism of action of these nanoparticles. PMID- 21971918 TI - Syntheses, structural characterization and properties of transition metal complexes of 5,5'-(1,4-phenylene)bis(1H-tetrazole) (H(2)bdt), 5',5''-(1,1' biphenyl)-4,4'-diylbis(1H-tetrazole) (H(2)dbdt) and 5,5',5''-(1,3,5 phenylene)tris(1H-tetrazole) (H(3)btt). AB - The hydrothermal chemistry of a variety of M(II)SO(4) salts with the tetrazole (Ht) ligands 5,5'-(1,4-phenylene)bis(1H-tetrazole) (H(2)bdt), 5',5''-(1,1' biphenyl)4,4'-diylbis(1H-tetrazole) (H(2)dbdt) and 5,5',5''-(1,3,5 phenylene)tris(1H-tetrazole) (H(3)btt) was investigated. In the case of Co(II), three phases were isolated, two of which incorporated sulfate: [Co(5)F(2)(dbdt)(4)(H(2)O)(6)].2H(2)O (1.2H(2)O), [Co(4)(OH)(2)(SO(4))(bdt)(2)(H(2)O)(4)] (2) and [Co(3)(OH)(SO(4))(btt)(H(2)O)(4)].3H(2)O (3.3H(2)O). The structures are three dimensional and consist of cluster-based secondary building units: the pentanuclear {Co(5)F(2)(tetrazolate)(8)(H(2)O)(6)}, the tetranuclear {Co(4)(OH)(2)(SO(4))(2)(tetrazolate)(6)}(4-), and the trinuclear {Co(3)(MU(3) OH)(SO(4))(2) (tetrazolate)(3)}(2-) for 1, 2, and 3, respectively. The Ni(II) analogue [Ni(2)(H(0.67)bdt)(3)].10.5H(2)O (4.10.5H(2)O) is isomorphous with a fourth cobalt phase, the previously reported [Co(2)(H(0.67)bat)(3)].20H(2)O and exhibits a {M(tetrazolate)(3/2)}(infinity) chain as the fundamental building block. The dense three-dimensional structure of [Zn(bdt)] (5) consists of {ZnN(4)}tetrahedra linked through bdt ligands bonding through N1,N3 donors at either tetrazolate terminus. In contrast to the hydrothermal synthesis of 1-5, the Cd(II) material (Me(2)NH(2))(3)[Cd(12)Cl(3)(btt)(8)(DMF)(12)].xDMF.yMeOH (DMF = dimethylformamide; x = ca. 12, y = ca. 5) was prepared in DMF/methanol. The structure is constructed from the linking of {Cd(4)Cl(tetrazolate)(8)(DMF)(4)}(1 ) secondary building units to produce an open-framework material exhibiting 66.5% void volume. The magnetic properties of the Co(II) series are reflective of the structural building units. PMID- 21971919 TI - Unfit for service: the implications of rising obesity for US military recruitment. AB - This paper contributes to the literature on the labor market consequences of unhealthy behaviors and poor health by examining a previously underappreciated consequence of the rise in obesity in the USA: challenges for military recruitment. Specifically, this paper estimates the percentage of the US military age population that exceeds the US Army's current active duty enlistment standards for weight-for-height and percent body fat, using data from the series of National Health and Nutrition Examination Surveys that spans 1959-2008. We calculate that the percentage of military-age adults ineligible for enlistment because they are overweight and overfat more than doubled for men and tripled for women during that time. As of 2007-2008, 5.7 million men and 16.5 million women exceeded the Army's enlistment standards for weight and body fat. We document disparities across race and education in exceeding the standards and estimate that a further rise of just 1% in weight and body fat would further reduce eligibility for military service by over 850 000 men and 1.3 million women. The paper concludes with a discussion of the implications of these findings for military recruitment and defense policy. PMID- 21971920 TI - The intussusception in patients with Crohn's disease: the role of the surgeon. PMID- 21971921 TI - Endoscopic red flags for the detection of high-risk serrated polyps: an observational study. AB - BACKGROUND AND STUDY AIMS: In routine practice, colonoscopy may fail to prevent colorectal cancer (CRC), especially in the proximal colon. A better endoscopic recognition of serrated polyps is important, as this pathway may explain some of the post-colonoscopy cancers. In this study, the endoscopic characteristics of serrated polyps were examined. PATIENT AND METHODS: This was a cross-sectional, single-center study of all consecutive patients referred for elective colonoscopy during 1 year. The endoscopists were familiarized with the detection and treatment of nonpolypoid colorectal lesions. Serrated polyps were classified into high risk serrated polyps, defined as dysplastic or large (>= 6 mm) proximal nondysplastic serrated polyps, and low risk serrated polyps including the remaining nondysplastic serrated polyps. Advanced colorectal neoplasms were defined as multiple (at least three),>= 10 mm in size, high grade dysplastic adenomas or CRC. RESULTS: A total of 2309 patients were included (46.1 % men, mean age 58.4 years), of whom 2.5 % (57) had at least one high risk serrated polyp and 13.9 % (322) had at least one advanced neoplasm. Overall, serrated polyps were more often nonpolypoid than adenomas (16.2 % vs. 11.1 %; P = 0.002). In total, 65 high risk serrated polyps were found, of which 43.1 % (28) displayed a nonpolypoid endoscopic appearance. Patients with advanced neoplasms were more likely to have synchronous high risk serrated polyps than patients without advanced neoplasms: OR 3.66 (95 % CI 2.03 - 6.61, P < 0.001). CONCLUSIONS: High risk serrated polyps are frequently nonpolypoid and are associated with synchronous advanced colorectal neoplasms. Advanced colorectal neoplasms may therefore be considered red flags for the presence of high risk serrated polyps. Detection, diagnosis, and treatment of high risk serrated lesions may be important targets to improve the quality of colonoscopic cancer prevention. PMID- 21971922 TI - New classification for probe-based confocal laser endomicroscopy in the colon. AB - BACKGROUND AND AIMS: Probe-based confocal laser endomicroscopy (pCLE; Cellvizio, Mauna Kea Technologies, Paris, France) enables in vivo histology during colonoscopy and may allow endoscopists to make real-time diagnoses. A collaboration of five experts proposed a new pCLE classification for colonic use. The aim of this study was to assess interobserver agreement and accuracy of the new pCLE classification in the colon. PATIENTS AND METHODS: Eligible patients were prospectively investigated by pCLE. A subset of 13 pCLE video sequences was reviewed post hoc for the establishment of a new classification, which comprised three vessel categories and seven crypt categories. All five blinded observers then scored another set of 102 video sequences, using the new classification. Histopathology was used as a reference standard. RESULTS: The interobserver agreements on vessel and crypt architecture were 'fair' with kappa values of 0.29 and 0.27, respectively. When the classification was reduced to neoplasia vs. non neoplasia (i.e. vessel or crypt type 3), overall agreement became 'moderate' (kappa = 0.56). Overall sensitivity and specificity for predicting neoplasia was 66 % and 83 %, respectively. When all observers agreed (69 % of videos), the corresponding figures became 80 % and 95 %. CONCLUSION: A new classification for pCLE in the colon had a 'moderate' interobserver agreement for differentiating neoplasia from non-neoplastic tissue in the colon. The overall accuracy (81 %) for predicting neoplasia was acceptable and became excellent (94 %) when all five observers agreed. Future research should focus on refinement and validation of the classification. PMID- 21971923 TI - Systematic review of endoscopic mucosal resection versus transanal endoscopic microsurgery for large rectal adenomas. AB - BACKGROUND AND STUDY AIMS: Large ( > 2 cm) rectal adenomas are currently treated by either transanal endoscopic microsurgery (TEM) or piecemeal endoscopic mucosal resection (EMR). The potential lower morbidity of EMR may become irrelevant if EMR is less effective. The aim of this study was to compare the safety and effectiveness of EMR and TEM for large rectal adenomas. PATIENTS AND METHODS: A systematic review of the literature published between January 1980 and January 2009 was conducted. Pooled estimates of the proportion of patients with recurrence or complications in EMR and TEM studies were compared using random effects meta-regression analysis. Early (after single intervention) and late (excluding re-treatment of residual adenoma detected within 3 months) recurrence rates were calculated. RESULTS: A total of 20 EMR studies and 48 TEM studies were included. No studies directly compared EMR with TEM. Mean polyp size was 31 mm (range 2 - 86 mm) for EMR vs. 37 mm (range 3 - 182 mm) for TEM (P = 0.02). Early recurrence rates were 11.2 % (95 % confidence interval [CI] 6.0 - 19.9) for EMR vs. 5.4 % (95 %CI 4.0 - 7.3) for TEM (P = 0.04). Late recurrence rates were 1.5 % (95 %CI 0.6 - 3.9) for EMR vs. 3.0 % (95 %CI 1.3 - 6.9) for TEM (P = 0.29). Postoperative complication rates were 3.8 % (95 %CI 2.8 - 5.3) for EMR vs. 13.0 % (95 %CI 9.8 - 17.0) for TEM (P < 0.001). CONCLUSIONS: After single intervention, EMR for large rectal adenomas appears to be less effective but safer than TEM. When outcome data for re-treatment of residual adenoma within 3 months are included, EMR and TEM seem equally effective. Nevertheless, the added morbidity of additional EMRs could not be accounted for in this analysis. A prospective randomized trial seems imperative before making recommendations concerning the treatment of large rectal adenomas. PMID- 21971924 TI - Combined endobronchial and endoscopic ultrasound-guided fine needle aspiration for mediastinal nodal staging of lung cancer. AB - BACKGROUND: Recently, transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been evaluated for mediastinal nodal staging (N staging) of lung cancer, as this technique is less invasive than mediastinoscopy and possibly more accurate than 18F-fluorodeoxyglucose positron emission tomography with computed tomography (PET-CT). However, EUS-FNA does not provide access to pretracheal and hilar lymph nodes. More recently, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been introduced as a novel technique for accessing pretracheal and hilar lymph nodes. Although the combined endoscopic approach of EUS-FNA and EBUS-TBNA is presumably more accurate than PET CT, only a few reports have quantitatively evaluated its diagnostic ability. Therefore, we prospectively assessed the diagnostic yield of this combined endoscopic approach for mediastinal N staging of lung cancer. METHODS: A consecutive series of 120 patients with suspected resectable lung cancer on CT findings underwent PET-CT and combined EUS-FNA/EBUS-TBNA. The accuracy and other diagnostic indices of the combined approach in mediastinal N staging were compared with those of PET-CT. RESULTS: Among the enrolled patients, a final pathological N stage was established in 110 patients. The accuracy of the combined approach using EUS-FNA and EBUS-TBNA was significantly higher than that of PET-CT (90.0 % vs. 73.6 %; P < 0.0001). The sensitivity, specificity, and positive and negative predictive values were respectively 71.8 %, 100 %, 100 %, and 86.6 % for the combined approach vs. 47.4 %, 87.5 %, 66.7 %, and 75.9 % for PET-CT. CONCLUSIONS: The combined endoscopic approach using EUS-FNA and EBUS-TBNA provided excellent diagnostic performance. Therefore, this approach is strongly recommended before surgery or mediastinoscopy to avoid futile thoracotomy and surgical intervention. PMID- 21971925 TI - Carbon dioxide insufflation vs. conventional saline irrigation for peroral video cholangioscopy. AB - BACKGROUND AND STUDY AIMS: Recent studies have evaluated the efficacy of peroral cholangioscopy (POCS) for diagnosis of biliary diseases. In order to obtain clear images with POCS, saline irrigation, which is performed to replace yellow bile, is carried out for an extended duration. The aim of this study was to evaluate the feasibility of replacing saline irrigation with CO2 insufflation during POCS. PATIENTS AND METHODS: A total of 36 patients who had bile duct lesions and were due to undergo POCS were enrolled in the study. Of these patients, 18 underwent POCS using saline irrigation followed by CO2 insufflation, and 18 patients underwent the reverse approach. The two methods were compared with regard to the time required to obtain a clear endoscopic image and the quality of the images. RESULTS: The median time required to obtain a clear endoscopic image using CO2 insufflation (5.0 min) was significantly shorter than that required for saline irrigation (22.5 min; P < 0.001). The quality of the endoscopic images obtained was similar in 27 cases. However, CO2 insufflation provided better images in four cases that showed an abundance of mucin or biliary sludge, and saline irrigation was superior to CO2 insufflation in five cases that showed severe stricture with bleeding and tall papillary lesions. CONCLUSIONS: CO2 insufflation during POCS can reduce procedure time and simplify cholangioscopy. The overall image quality was similar to that obtained with conventional saline irrigation. PMID- 21971926 TI - Endoscopic management of malignant biliary obstruction by means of covered metallic stents: primary stent placement vs. re-intervention. AB - BACKGROUND AND STUDY AIMS: Recent progress in chemotherapy has prolonged the survival of patients with malignant biliary strictures, leading to increased rates of stent occlusion. Occlusion of covered metallic stents now occurs in about half of all patients with malignant biliary strictures. The removal of metallic stents followed by placement of a second stent has been attempted, but outcomes remain controversial. The aim of the current study was to evaluate the effectiveness and safety of the primary placement and secondary placement (re intervention) of covered metallic stents and to assess the feasibility and safety of stent removal. PATIENTS AND METHODS: The study included 186 patients with unresectable malignant biliary strictures who underwent primary stent placement between October 2001 and March 2010. Covered biliary self-expandable metal stents (SEMSs) were removed in 39 of these patients, and 36 underwent re intervention. The patency times, occlusion rates of the first stent and re intervention, success rates of stent removal, and complications were investigated. RESULTS: Covered SEMSs were placed in 186 patients. The median patency time of the first stent was 352 days. Stent occlusion occurred in 48.9 % of the patients and was mainly caused by debris or food residue (37 %), dislocation (19 %), and migration with hyperplasia (19 %). Stent removal was attempted in 50 patients and was successful without complication in 39 (78 %). Most of the patients in whom stent removal was unsuccessful had migration with hyperplasia. The median patency time of the second stent was 263 days. The stent patency time did not significantly differ between the first and the second stent. CONCLUSIONS: Covered SEMSs could be safely removed at the time of stent occlusion. Patency rates were similar for initial stent placement and re intervention. PMID- 21971927 TI - Endoscopic transesophageal vs. thoracoscopic removal of mediastinal lymph nodes: a prospective randomized trial in a long term animal survival model. AB - BACKGROUND AND STUDY AIMS: In cases where biopsies remain inconclusive, removal of mediastinal lymph nodes for further analysis requires surgical means. Natural orifice transluminal endoscopic surgery (NOTES) procedures allow incision/closure of the gut wall, which might enable endoscopic excision of pre-marked nodes. The aims of the current study were to investigate the feasibility, safety, and reproducibility of lymph node generation in an animal model to enable endoscopic ultrasound-guided (EUS) lymph node removal (ELR) using transesophageal NOTES access/closure and to compare this procedure with thoracoscopic lymph node removal (TLR) in a randomized long term survival animal study. PATIENTS AND METHODS: Lymph node creation using graphite injection was performed in 12 pigs. After randomization into ELR and TLR groups, lymph nodes were marked with newly developed anchors under EUS guidance and removed using either ELR or TLR. ELR included incision of the esophageal wall and closure after lymph node removal. The main outcome measures were success in lymph node generation, technical success of lymph node removal, complications, and comparability of ELR and TLR. RESULTS: Generation of lymph nodes proved successful in all animals in 46/48 sites injected (96 %). Anchors were placed through the selected nodes in a mean of 9.4 minutes. TLR and ELR were successful in all cases. One bleeding occurred during esophageal incision in ELR, which was stopped endoscopically. After lymph node removal, endoscopic suturing of the incision took a mean of 18 minutes. Procedure time was longer for ELR than TLR (mean 48 vs. 42 minutes). All animals survived the procedures. Autopsy after 4 weeks showed two thoracic wall abscesses in the TLR group and none in the ELR group. Microscopic analysis revealed well healed esophageal scars. CONCLUSION: ELR proved to be feasible in this limited sample size and complications were not observed more frequently in this group than in the TLR group. PMID- 21971928 TI - Esophageal tuberculosis: a microgranuloma visualized by narrow-band imaging magnifying endoscopy. PMID- 21971929 TI - A comparison of high definition-image enhanced colonoscopy and standard white light colonoscopy for colorectal polyp detection. AB - BACKGROUND AND STUDY AIMS: Colonoscopy is widely used to detect and remove precancerous polyps, but fails to detect some polyps. Recent studies evaluating different image-enhanced methods have revealed conflicting results. The efficacy of colonoscopy imaging with simultaneous use of commercially available improvements, including high definition narrow band imaging (HD-NBI), and monochromatic charge-coupled device (CCD) video, was compared with a widely used standard definition white light (SDWL) colonoscopy system for detecting colorectal polyps. The primary aim was to determine whether the combination of image-enhanced colonoscopy systems resulted in fewer missed polyps compared with conventional colonoscopy. PATIENTS AND METHODS: In a randomized controlled trial (Clinicaltrials.gov. study number NCT00825292) patients having routine screening and surveillance underwent tandem colonoscopies with SDWL and image-enhanced (HD NBI) colonoscopy. The main outcome measurement was the per-polyp false-negative ("miss") rate. Secondary outcomes were adenoma miss rate, and per-patient polyp and adenoma miss rates. RESULTS: 100 patients were randomized and 96 were included in the analysis. In total, 177 polyps were detected; of these, 72 (41 %) were adenomatous. Polyp and adenoma miss rates for SDWL colonoscopy were 57 % (60/105) and 49 % (19/39); those for image-enhanced colonoscopy were 31 % (22/72) and 27 % (9/33) (P = 0.005 and P = 0.036 for polyps and adenomas, respectively). Image-enhanced and SDWL approaches had similar per-patient miss rates for polyps (6/35 vs. 9/32, P = 0.27) and adenomas (4/22 vs. 8/20, P = 0.11). CONCLUSIONS: Utilization of multiple recent improvements in image-enhanced colonoscopy was associated with a reduced miss rate for all polyps and for adenomatous polyps. It is not known which individual feature or combination of image-enhancement features led to the improvement. PMID- 21971930 TI - The histone deacetylase inhibitor trichostatin A alters microRNA expression profiles in apoptosis-resistant breast cancer cells. AB - The development of drug resistance represents a major complication in the effective treatment of breast cancer. Epigenetic therapy, through the use of histone deacetylase inhibitors (HDACi) or demethylation agents, is an emerging area of therapeutic targeting in a number of ontological entities, particularly in the setting of aggressive therapy-resistant disease. Using the well-described HDAC inhibitor trichostatin A (TSA) we demonstrate the suppression of in vitro clonogenicity in the previously described apoptosis-resistant MCF-7TN-R breast carcinoma cell line. Additionally, recent work has demonstrated that these agents can alter the expression profile of microRNA signatures in malignant cells. Using an unbiased microRNA microarray analysis, changes in miRNA expression of MCF-7TN R cells treated with TSA for 24 h were analyzed. We observed significant up regulation of 22 miRNAs and down-regulation of 10 miRNAs in response to TSA treatment. Our results demonstrate that the HDACi, TSA, exerts anticancer activity in the apoptosis-resistant MCF-7TN-R breast carcinoma cell line. This activity is correlated with TSA alteration of microRNA expression profiles indicative of a less aggressive phenotype. PMID- 21971932 TI - Glucosamine-linked near-infrared fluorescent probes for imaging of solid tumor xenografts. AB - PURPOSE: Near-infrared fluorescence (NIRF) imaging is an attractive technique for studying diseases at the molecular level in vivo. Glucose transporters are often used as targets for in vivo imaging of tumors. The efficiency of a tumor-seeking fluorescent probe can be enhanced by attaching one or more glucosamine (GlcN) moieties. This study was designed to evaluate the use of previously developed GlcN-linked NIRF probes for in vitro and in vivo optical imaging of cancer. PROCEDURES: Cellular uptake of the probes (1 MUM) was investigated in monolayer cultures of luciferase-expressing PC3 (PC3-luc) cells. The prostate tumors were established as subcutaneous xenografts using PC3-luc cells in nude mice. The biodistributions and tumor-targeting specificities of cypate (cyp), cypate-D: (+)-glucosamine (cyp-GlcN), and D: -(+)-gluosamine-cypate-D: -(+)-gluosamine (cyp 2GlcN) were studied. The tumor, muscle, and major organs were collected for ex vivo optical imaging. RESULTS: The tumor cell uptake of the probe containing two glucosamine residues, cyp-2GlcN, was significantly higher than the uptake of both the probe with one glucosamine residue, cyp-GlcN, and the probe without glucosamine, cyp only. Similarly, in in vivo experiments, cyp-2GlcN demonstrated higher maximum fluorescence intensity and longer residence lifetime in tumors than cyp-GlcN or cyp. The ex vivo biodistribution analysis revealed that tumor uptake of cyp-2GlcN and cyp-GlcN was four- and twofold higher than that of cyp at 24 h post-injection, respectively. CONCLUSION: Both cyp-GlcN and cyp-2GlcN NIRF probes exhibited good tumor-targeting properties in prostate cancer cell cultures and live mice. The cyp-2GlcN probe showed the highest uptake with good retention characteristics in vivo. The uptake of cyp-2GlcN and cyp-GlcN is likely mediated by glucosamine-recognizing transporters. The uptake mechanism is being explored further for developing cypate-glucosamine-based probes for in vivo imaging. PMID- 21971933 TI - Spontaneous occurrence of dissecting aneurysms in the region of the ductus arteriosus in four-day-old Wistar rat pups. AB - Dissecting aortic aneurysms, generally involving the thoracic aorta, have been shown to be caused by specific aliphatic amines in developing rats. Whether such lesions might occur spontaneously in control rats is not known. Therefore, in this study, 1,016 four-day-old, untreated rats culled from ongoing scheduled breeding studies were subjected to gross and histopathological examination in order to create a background control data base on the incidence of spontaneous aortic dissecting aneurysms. Two animals (0.2%) were found to have small dissecting aortic aneurysms, and an additional 2 (0.2%) had only hemorrhagic lesions. All of these lesions were limited to the region of the ductus arteriosus. An additional 18 findings were judged to be artifacts. These findings suggest that small vascular dissections may rarely occur in the aortic arch adjacent to the ductus arteriosus. Special attention should be paid in experimental studies to avoid confusing these small spontaneous lesions with treatment-induced lesions or artifacts. PMID- 21971931 TI - Non-surgical approach to the benign nodular goiter: new opportunities by recombinant human TSH-stimulated 131I-therapy. AB - The optimal treatment strategy in a goiter patient depends--among other factors- on goiter size, the degree of cosmetic or compressive symptoms, the age of the patient, the impact on the upper airways, the wish to maintain normal thyroid function, the ability of the thyroid gland to take up (131)I, and the possibility of thyroid malignancy. When treatment is warranted in a patient with benign goiter, the choice usually stands between surgery and (131)I-therapy. Focal destructive treatment, by ethanol sclerotherapy or interstitial laser photocoagulation, may be considered in patients with a solitary benign nodule. If thyroid hyperfunction due to nodular autonomy is the dominant problem, life-long anti-thyroid drug treatment may be relevant in elderly individuals. With the advent of recombinant human TSH (rhTSH) stimulation the goiter reduction following (131)I-therapy is significantly enhanced and this treatment is of particular benefit, as compared with conventional (131)I-therapy, in patients with a low baseline thyroid (131)I uptake and a large goiter. If the rhTSH dose does not exceed 0.1 mg the risk of temporary hyperthyroidism and acute thyroid swelling is low. Since patient satisfaction seemingly is not improved by the greater goiter reduction obtained by rhTSH-stimulated (131)I-therapy, and permanent hypothyroidism is more frequent, it may be more relevant to reduce the administered radioactivity equivalent to the rhTSH-induced increase in the thyroid (131)I uptake. Future large-scale well-controlled studies should explore this strategy, with focus on cost-benefit and quality of life. A major hindrance of widespread and routine use of rhTSH-stimulated (131)I-therapy is its present status as an off-label treatment. PMID- 21971934 TI - The use of immunohistochemistry for biomarker assessment--can it compete with other technologies? AB - A morphology-based assay such as immunohistochemistry (IHC) should be a highly effective means to define the expression of a target molecule of interest, especially if the target is a protein. However, over the past decade, IHC as a platform for biomarkers has been challenged by more quantitative molecular assays with reference standards but that lack morphologic context. For IHC to be considered a "top-tier" biomarker assay, it must provide truly quantitative data on par with non-morphologic assays, which means it needs to be run with reference standards. However, creating such standards for IHC will require optimizing all aspects of tissue collection, fixation, section thickness, morphologic criteria for assessment, staining processes, digitization of images, and image analysis. This will also require anatomic pathology to evolve from a discipline that is descriptive to one that is quantitative. A major step in this transformation will be replacing traditional ocular microscopes with computer monitors and whole slide images, for without digitization, there can be no accurate quantitation; without quantitation, there can be no standardization; and without standardization, the value of morphology-based IHC assays will not be realized. PMID- 21971935 TI - Sponsor-CRO practices that facilitate the creation of a high-quality pathology report: a pharmaceutical sponsor's perspective. PMID- 21971936 TI - Counterpoint to "Analysis of unbiased histopathology data from rodent toxicity studies (or, are these groups different enough to ascribe to treatment?)". PMID- 21971937 TI - Prolactin-induced mammary tumorigenesis is not a rodent-specific response. PMID- 21971939 TI - The effects of limb alignment on anterior cruciate ligament graft tunnel positions estimated from plain radiographs. AB - PURPOSE: The aims of this study were (1) to evaluate the femoral tunnel position after anatomic double-bundle and nonanatomic single-bundle reconstruction; (2) to evaluate the influence of rotation of the femur caused by limb malalignment on measurements of the position of the femoral ACL tunnel aperture relative to Blumensaat's line. METHODS: 3D CT scans were performed in 5 patients after anatomic double-bundle reconstruction and 5 patients after nonanatomic single bundle reconstruction. Digitally reconstructed lateral radiographs were generated from the 3D CT scans to determine the tunnel position on the femur along and perpendicular to Blumensaat's line. The femur was then rotated to simulate internal/external and varus/valgus rotations from 0 degrees to 15 degrees in 5 degrees increments. At each rotated bone position, tunnel position relative to Blumensaat's line was calculated and the difference from the lateral radiograph was calculated. RESULTS: After double-bundle reconstruction, the AM tunnel was located at 31.5 (+/-5.0) % along Blumensaat's line and 29.7 (+/-13.6) % perpendicular to Blumensaat's line, and the PL tunnel at 36.2 (+/-12.9) % along Blumensaat's line and 34.2 (+/-7.6) % perpendicular to Blumensaat's line. Valgus greater than 10 degrees significantly affected the assessment of tunnel position (P = 0.043). After nonanatomic single-bundle reconstruction, the tunnel position was 35.4 (+/-15.0) % along Blumensaat's line and -2.7 (+/-19.4) % perpendicular to Blumensaat's line. Internal rotation of more than 10 degrees significantly affected the assessment of tunnel position (P = 0.043). CONCLUSIONS: Tunnel position after anatomic double-bundle reconstruction and nonanatomic single bundle reconstruction can be determined on lateral radiographs. However, valgus and internal rotation of more than 10 degrees can introduce significant errors in tunnel position estimates. LEVEL OF EVIDENCE: Case series, Level IV. PMID- 21971938 TI - Tibial component designs in primary total knee arthroplasty: should we reconsider all-polyethylene component? AB - PURPOSE: Despite the frequency with which total knee arthroplasties (TKAs) are performed, whether they are best performed using all-polyethylene or metal-backed tibial components remains a controversy. The aim of the present study was to determine the advantages and disadvantages of metal-backed compared with all polyethylene tibial components during TKAs through an evaluation of current literature. METHODS: A meta-analysis and systematic review of randomized and non randomized comparative studies comparing metal-backed with all-polyethylene tibial components during TKAs were performed. The focus of the analysis was on the outcomes of knee score, range of motion (ROM), quality of life, implant alignment, tibial migration, radiolucent line, complication, reoperation, and implant survivorship. RESULTS: A total of 10 randomized/quasi-randomized controlled trials and 13 non-randomized comparative studies assessing 19,767 TKAs were eligible. On the basis of these studies, no significant differences were found between the 2 groups with regard to knee score, ROM, quality of life, complication, and reoperation. The findings indicated that using all-polyethylene tibial components is associated with lower continuous migration rate compared with metal-backed tibial components. Only 13 studies provided adequate data on implant survivorship during intermediate or long-term follow-up. Of these, 9 found that no statistical significance existed between the 2 groups. The other 3 studies found that using all-polyethylene components yielded a higher survival rate than using metal-backed components. CONCLUSIONS: Metal-backed tibial components had no obvious advantages over all-polyethylene tibial components in TKAs. However, this finding should be interpreted with caution due to publication bias, low methodological quality of the included studies, and different surgical interventions. LEVEL OF EVIDENCE: Therapeutic study (systematic review and meta analysis), Level III. PMID- 21971940 TI - Fibrocartilage in various regions of the human glenoid labrum. An immunohistochemical study on human cadavers. AB - PURPOSE: The nature and the distribution of fibrocartilage at the human glenoid labrum are unclear, and a better understanding may help to restore its function in open and arthroscopic Bankart repair. Aim of this study was to describe the fibrocartilage extent within the labrum at clinically relevant sites of the glenoid in order to relate the molecular composition of the labrum to its mechanical environment. METHODS: Twelve fresh frozen human cadaveric shoulders (mean age 38 years) were obtained, and sections perpendicular to the glenoid rim at the 12, 2, 3, 4, 6 and 9 o' clock position were labelled with antibodies against collagen I and II, aggrecan and link protein. RESULTS: A fibrocartilaginous transition zone with a characteristic collagen fibre orientation was found in 81% of cases, evenly distributed (83-92%) around the glenoid rim. The percentage of labrum cross-sectional area comprised of fibrocartilage averaged 28% and ranged from 26% at 12 o'clock on the glenoid clock face to 30% at 3 o'clock. The highest amount of fibrocartilage (82%) was found in the region neighbouring the hyaline articular cartilage. In the region beyond the bony edge of the glenoid, fibrocartilage cross-sectional area did not exceed 12-17%. CONCLUSION: Fibrocartilage is present at all examined positions around the glenoid rim and constitutes up to 1/3 of the cross-sectional area of the labrum. In turn, the percentage of fibrocartilage in different regions of its cross-section varies considerably. The findings suggest that the penetration of fibrocartilaginous tissue may be reduced by avoiding the highly fibrocartilage transition zone during restoration of labral detachment. PMID- 21971942 TI - Prognosis of pneumocystis pneumonia complicated in patients with rheumatoid arthritis (RA) and non-RA rheumatic diseases. AB - Clinical presentation of pneumocystis pneumonia (PCP) during immunosuppressive therapy for rheumatic diseases was compared between patients with rheumatoid arthritis (RA; n = 7) and those without RA (non-RA; n = 12) based on a chart review. Both RA and non-RA patients with PCP were treated with methotrexate (n = 7) combined with steroids (n = 6) and/or biologics (n = 4). RA-PCP patients were found to have a higher mortality rate than non-RA-PCP patients (3/7 vs. 0/12, respectively; p = 0.036) due to a later exacerbation of interstitial pneumonia and a higher presentation rate of diffuse pulmonary lesions (4/7 vs. 1/12, respectively; p = 0.036) despite lower mean levels of serum beta-D: -glucan (314 +/- 214 vs. 1139 +/- 1114 pg/ml, respectively; p = 0.02) that suggested a lower burden of Pneumocystis jirovecii. In conclusion, PCP in RA patients with existing pulmonary lesions may trigger subsequent progression to lethal interstitial pneumonia. PMID- 21971941 TI - A novel nano-structured porous polycaprolactone scaffold improves hyaline cartilage repair in a rabbit model compared to a collagen type I/III scaffold: in vitro and in vivo studies. AB - PURPOSE: To develop a nano-structured porous polycaprolactone (NSP-PCL) scaffold and compare the articular cartilage repair potential with that of a commercially available collagen type I/III (Chondro-Gide) scaffold. METHODS: By combining rapid prototyping and thermally induced phase separation, the NSP-PCL scaffold was produced for matrix-assisted autologous chondrocyte implantation. Lyophilizing a water-dioxane-PCL solution created micro and nano-pores. In vitro: The scaffolds were seeded with rabbit chondrocytes and cultured in hypoxia for 6 days. qRT-PCR was performed using primers for sox9, aggrecan, collagen type 1 and 2. In vivo: 15 New Zealand White Rabbits received bilateral osteochondral defects in the femoral intercondylar grooves. Autologous chondrocytes were harvested 4 weeks prior to surgery. There were 3 treatment groups: (1) NSP-PCL scaffold without cells. (2) The Chondro-Gide scaffold with autologous chondrocytes and (3) NSP-PCL scaffold with autologous chondrocytes. Observation period was 13 weeks. Histological evaluation was made using the O'Driscoll score. RESULTS: In vitro: The expressions of sox9 and aggrecan were higher in the NSP-PCL scaffold, while expression of collagen 1 was lower compared to the Chondro-Gide scaffold. In vivo: Both NSP-PCL scaffolds with and without cells scored significantly higher than the Chondro-Gide scaffold when looking at the structural integrity and the surface regularity of the repair tissue. No differences were found between the NSP-PCL scaffold with and without cells. CONCLUSION: The NSP-PCL scaffold demonstrated higher in vitro expression of chondrogenic markers and had higher in vivo histological scores compared to the Chondro-Gide scaffold. The improved chondrocytic differentiation can potentially produce more hyaline cartilage during clinical cartilage repair. It appears to be a suitable cell-free implant for hyaline cartilage repair and could provide a less costly and more effective treatment option than the Chondro-Gide scaffold with cells. PMID- 21971944 TI - Psychiatric comorbidities in autism spectrum disorders: findings from a Danish Historic Birth Cohort. PMID- 21971943 TI - Effects of intravenous immunoglobulin therapy in Japanese patients with polymyositis and dermatomyositis resistant to corticosteroids: a randomized double-blind placebo-controlled trial. AB - High-dose intravenous immunoglobulin (IVIG) therapy has been effective in treating various autoimmune and systemic inflammatory diseases. Here, we assessed the efficacy and safety of IVIG therapy with polyethylene glycol-treated human IgG (drug code GB-0998) for patients with corticosteroid-refractory polymyositis (PM) and dermatomyositis (DM) by means of a randomized, double-blind, placebo controlled study. We randomly assigned 26 subjects (16 PM and 10 DM) to receive either GB-0998 or placebo. Intragroup comparison in the GB-0998 group showed statistically significant improvements due to GB-0998 administration in the primary endpoint (manual muscle test score) and secondary endpoints (serum creatine kinase level and activities of daily living score). However, significant improvements were also found in the placebo group, and comparison of the GB-0998 group with the placebo group did not show any significant difference between the groups. We discuss possible reasons for the absence of a clear intergroup difference in efficacy. Nineteen adverse drug reactions were observed in 11 of 26 subjects (42.3%), of which 2 events (decreased muscle strength and increased serum creatine kinase) were assessed as serious; however, they are previously known events. These results indicate that GB-0998 can be safely used with the same precautions as other current IVIG therapy. PMID- 21971945 TI - Effects of an aging pulmonary system on expiratory flow limitation and dyspnoea during exercise in healthy women. AB - Aging related changes in pulmonary function may make older women (OW) more susceptible to expiratory flow limitation (EFL) and lead to higher dyspnoea ratings during exercise relative to young women (YW). Accordingly, the purpose of this study was to compare sensory responses and EFL susceptibility and magnitude in 8 YW (29 +/- 7 years) and 8 healthy OW (64 +/- 3 years) matched for percentage predicted forced vital capacity (% predicted FVC) and % predicted forced expiratory volume in 1 s. EFL was calculated as the percent overlap between tidal flow-volume loops during maximal exercise and the maximal expiratory flow-volume (MEFV) curve. Peak oxygen consumption (V'O(2peak)) was lower in the OW compared to the YW (29.4 +/- 3.6 vs. 49.1 +/- 8.9 ml kg(-1) min(-1), P < 0.05) as was maximal ventilation (73.7 +/- 18.4 vs. 108.7 +/- 14.1 l min(-1), P < 0.05). EFL at maximal exercise was present in 2 of 8 YW and in 5 of 8 OW. There were no significant differences in the magnitude of EFL between OW (23 +/- 24, range: 0 69 %EFL) and YW (9 +/- 18, range: 0-46 %EFL, P = 0.21). The magnitude of EFL in OW was inversely related to % predicted FVC (r = -0.69, P = 0.06), but this relationships was not observed in the YW (r = -0.23, P = 0.59). The OW consistently reported greater dyspnoea and leg discomfort for any given absolute work rate, but not when work was expressed as a percentage of maximum. Reduced ventilatory and exercise capacities may cause OW to be more susceptible to EFL during exercise and experience greater dyspnoea relative to YW for a standardized physical task. PMID- 21971947 TI - The spatio-temporal patterning of Hoxa9 and Hoxa13 in the developing zebrafish enteric nervous system. AB - BACKGROUND: Hirschsprung's disease is characterised by the absence of ganglion cells in the distal bowel, a process which is controlled by complex genetic pathways. Homeobox genes have a major role in gut development and this is depicted by the enteric Hox code which describes the different spatial and temporal expression of Hox genes. Hoxa9 and Hoxa13 mutations have been discovered in patients with Hirschsprung's disease (HD). The aim of this study was to determine the spatio-temporal pattern of Hoxa9 and Hoxa13 in enteric nervous system (ENS) development using the zebrafish model. METHODS: Purified plasmids that contained the gene of interest were obtained and inoculated into culture medium to exponentially increase the number of bacteria containing the plasmid. Cells were then harvested by centrifugation and plasmid DNA was extracted, which was then linearised and precipitated. RNA digoxigenin-labelled probes were made by in vitro transcription reaction. In situ hybridisation was carried out using these probes on zebrafish embryos which were collected from 24 to 120 h post fertilisation (hpf), by which time the zebrafish intestine is fully developed. Embryos were then mounted in glycerol and imaged using an Olympus B40 microscope and images were taken using an Olympus Super F1.8 digital camera. RESULTS: At 24 hpf, Hoxa9 expression is seen in the forebrain and hindbrain and also in the very distal myotome whereas Hoxa13 expression, however, is seen only at the forebrain and hindbrain. At 48 hpf, Hoxa9- and Hoxa13-labelled cells are seen migrating distally from the forebrain into the notochord and spinal cord. At 72 hpf, Hoxa9 labelled cells can be seen throughout the spinal cord whereas Hoxa13 positive cells are seen migrating down from the spinal cord and in the proximal gut. By 96 hpf, Hoxa9- and Hoxa13-labelled cells have migrated down the full length of the spinal cord and along the proximal and mid intestine. By 120 hpf, Hoxa9 and Hoxa13 positive cells can be seen along the entire length of the zebrafish intestine. CONCLUSIONS: These results show further evidence that Hoxa9 and Hoxa13 are involved in the early and organised patterning of ENS development in the zebrafish model. PMID- 21971948 TI - Influencing the electronic interaction in diferrocenyl-1-phenyl-1H-pyrroles. AB - Functionalised diferrocenyl-1-phenyl-1H-pyrroles were synthesised using Negishi C,C cross-coupling reactions. The influence of different substituents at the phenyl moiety on the electronic interaction was studied using electrochemistry (cyclic and square-wave voltammetry) and spectro-electrochemistry (in situ UV/Vis NIR spectroscopy). The ferrocenyl moieties gave rise to two sequential, reversible redox processes in each of the diferrocenyl-1-phenyl-1H-pyrroles. The observed DeltaE(1/2) values (DeltaE(1/2) = difference between first and second oxidation) range between 420 and 480 mV. A linear relationship between the Hammett constants sigma of the substituents and the separation of the redox potentials exists. The NIR measurements confirm electronic communication between the iron centers as intervalence charge transfer (IVCT) absorptions were observed in the corresponding mixed-valent monocationic species. All compounds were classified as class II systems according to Robin and Day (M. B. Robin and P. Day, Adv. Inorg. Chem., 1967, 10, 247-423). The oscillator strength of the charge transfer transition highly depends on the electron donating or electron withdrawing character of the phenyl substituents. This enables direct tuning of the intermetallic communication by simple modification of the molecule's functional group. Hence, this series of molecules may be regarded as model compounds for single molecule transistors. PMID- 21971946 TI - Apoptosis sensitizers enhance cytotoxicity in hepatoblastoma cells. AB - PURPOSE: Drug resistance remains a major challenge for the treatment of high-risk hepatoblastoma (HB). To enhance effectiveness of chemotherapy we modulate apoptosis in HB cells in vitro. METHODS: Viability was monitored in HB cells (HuH6, HepT1) and fibroblasts in monolayer and spheroid cultures treated with ABT 737, obatoclax, HA14-1, and TW-37 and each in combination with CDDP, etoposide, irinotecan, paclitaxel, and DOXO in a MTT assay. Western blot analyses were performed to determine expressions of pro- and anti-apoptotic proteins. RESULTS: Obatoclax and ABT-737 led to a dose-dependent decrease of viability in HB cells at concentrations above 0.3 MUM. TW-37 and HA14-1 were less effective. ABT-737 and obatoclax had additive effects when combined with CDDP, etoposide, irinotecan, paclitaxel, or DOXO. This was also observed for fibroblast, however, for higher drug concentrations. In spheroid cultures, relative expression of Bcl XL was increased, Bax was decreased, Mcl-1 was low, and Bcl-2 was not detected compared to 2D cultures, denoting an anti-apoptotic state in spheroids. Obatoclax and ABT-737 have overcome the resistance to CDDP. HuH6 cells have shown higher susceptability for apoptosis sensitizers than HepT1. CONCLUSION: The data provide evidence that ABT-737 and obatoclax might improve treatment results in children with HB. PMID- 21971950 TI - Methodological, ethical, and legal considerations in drug court research. AB - Since their inception in the late 1980s, drug courts have become the most prevalent specialty court in the United States. A large body of outcome research conducted over the past two decades has demonstrated that drug courts effectively reduce drug use and criminal recidivism, which has led to the rapid proliferation of these courts. Importantly, drug court research has flourished despite the many challenges faced by researchers when working with a vulnerable population of justice-involved substance users. In this article, we highlight the most common methodological, ethical, and legal challenges encountered in drug court research, and discuss ways in which researchers can overcome these challenges to conduct high-quality research. Drug court research exemplifies how rigorous empirical investigation can be accomplished in the criminal justice system, and it can serve as a useful model for researchers working in other parts of the judicial system. PMID- 21971951 TI - Predicting the severity of acute pancreatitis: choose the right horse before hitching the cart. PMID- 21971952 TI - Ginsenoside Re lowers blood glucose and lipid levels via activation of AMP activated protein kinase in HepG2 cells and high-fat diet fed mice. AB - Ginsenoside Re is a protopanaxatriol-type saponin isolated from Panax ginseng berry. Although anti-diabetic and anti-hyperlipidemic effects of Re have been reported by several groups, its mechanism of action is largely unknown until now. Here, we examine anti-diabetic and anti-hyperlipidemic activities of Re and action mechanism(s) in human HepG2 hepatocytes and high-fat diet fed C57BL/6J mice. Re suppresses the hepatic glucose production via induction of orphan nuclear receptor small heterodimer partner (SHP), and inhibits lipogenesis via suppression of sterol regulatory element binding protein-1c (SREBP-1c) and its target gene [fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD1)] transcription. These effects were mediated through activation of AMP-activated protein kinase (AMPK), and abolished when HepG2 cells were treated with an AMPK inhibitor, Compound C. C57BL/6J mice were randomly divided into five groups: regular diet fed group (RD), high-fat diet fed group (HFD) and the HFD plus Re (5, 10, 20 mg/kg) groups. Re treatment groups were fed a high-fat diet for 6 weeks, and then orally administered Re once a day for 3 weeks. The in vitro results are likely to hold true in an in vivo experiment, as Re markedly lowered blood glucose and triglyceride levels and protected against hepatic steatosis in high-fat diet fed C57BL/6J mice. In conclusion, the current study suggest that ginsenoside Re improves hyperglycemia and hyperlipidemia through activation of AMPK, and confers beneficial effects on type 2 diabetic patients with insulin resistance and dyslipidemia. PMID- 21971953 TI - Cascade cyclization, dipolar cycloaddition of azomethine imines for the synthesis of pyrazolidines. AB - A tandem multi-step, one-pot reaction of aldehydes with hydrazines has been used for the preparation of tetrahydropyrazoles and dihydropyrazoles. The chemistry involves condensation then cyclization, followed by inter- or intramolecular dipolar cycloaddition of the resulting azomethine imine intermediates. The intramolecular cycloaddition gives fused tricyclic compounds as single diastereoisomers. The intermolecular cycloaddition was successful with a variety of activated alkene and alkyne dipolarophiles. PMID- 21971954 TI - The taming of CN7(-): the azidotetrazolate 2-oxide anion. AB - The highly sensitive 5-azidotetrazolate anion was oxidized to its corresponding N oxide by aqueous oxidation in a buffered oxone solution to the azidotetrazolate 2 oxide anion. After acidic extraction and neutralization with ammonia, the ammonium salt was isolated. Several energetic salts of this novel anion were prepared from the ammonium salt, and in all cases were found to be of lower sensitivity than the corresponding 5-azidotetrazolate salt while still being highly sensitive towards mechanical stimuli. Explosive performances (detonation velocity, detonation pressure) of applicable salts were also found to be higher than the non-N-oxide variants. Preparation of the free acid 2-hydroxy-5 azidotetrazole was achieved by protonation of the anion and identified by NMR spectroscopy, whereas the majority of the azidotetrazolate 2-oxide salts have unequivocal crystallographic proof. PMID- 21971955 TI - Multiscale modeling of composite materials: a roadmap towards virtual testing. AB - A bottom-up, multiscale modeling approach is presented to carry out high-fidelity virtual mechanical tests of composite materials and structures. The strategy begins with the in situ measurement of the matrix and interface mechanical properties at the nanometer-micrometer range to build up a ladder of the numerical simulations, which take into account the relevant deformation and failure mechanisms at different length scales relevant to individual plies, laminates and components. The main features of each simulation step and the information transferred between length scales are described in detail as well as the current limitations and the areas for further development. Finally, the roadmap for the extension of the current strategy to include functional properties and processing into the simulation scheme is delineated. PMID- 21971956 TI - Immune and inflammatory gene signature in rat cerebrum in subarachnoid hemorrhage with microarray analysis. AB - Cerebral vasospasm following subarachnoid hemorrhage (SAH) has been studied in terms of a contraction of the major cerebral arteries, but the effect of cerebrum tissue in SAH is not yet well understood. To gain insight into the biology of SAH expressing cerebrum, we employed oligonucleotide microarrays to characterize the gene expression profiles of cerebrum tissue at the early stage of SAH. Functional gene expression in the cerebrum was analyzed 2 h following stage 1-hemorrhage in Sprague-Dawley rats. mRNA was investigated by performing microarray and quantitative real-time PCR analyses, and protein expression was determined by Western blot analysis. In this study, 18 upregulated and 18 downregulated genes displayed at least a 1.5-fold change. Five genes were verified by real-time PCR, including three upregulated genes [prostaglandin E synthase (PGES), CD14 antigen, and tissue inhibitor of metalloproteinase 1 (TIMP1)] as well as two downregulated genes [KRAB-zinc finger protein-2 (KZF-2) and gamma-aminobutyric acid B receptor 1 (GABA B receptor)]. Notably, there were functional implications for the three upregulated genes involved in the inflammatory SAH process. However, the mechanisms leading to decreased KZF-2 and GABA B receptor expression in SAH have never been characterized. We conclude that oligonucleotide microarrays have the potential for use as a method to identify candidate genes associated with SAH and to provide novel investigational targets, including genes involved in the immune and inflammatory response. Furthermore, understanding the regulation of MMP9/TIMP1 during the early stages of SAH may elucidate the pathophysiological mechanisms in SAH rats. PMID- 21971957 TI - Appropriate application of ZIP for PKMzeta inhibition, LTP reversal, and memory erasure. PMID- 21971958 TI - Systematic review of escalated imatinib doses compared with sunitinib or best supportive care, for the treatment of people with unresectable/metastatic gastrointestinal stromal tumours whose disease has progressed on the standard imatinib dose. AB - INTRODUCTION: We conducted a systematic review of evidence on the effectiveness of imatinib at escalated doses of 600 mg/day or 800 mg/day for treatment of adults with unresectable or metastatic gastrointestinal stromal tumours (GIST), following progression on imatinib at the 400 mg/day dose, compared with sunitinib and/or 'best supportive care'. METHODS: Electronic searches were undertaken to identify relevant randomised controlled trials (RCTs), non-randomised studies, and case series reporting outcome data on survival, quality of life or adverse events. Titles and abstracts were screened by two reviewers and full text reports of potentially relevant studies assessed for inclusion. Included studies were quality assessed by two reviewers and data were extracted. Five studies reported data on the relevant population and were included. RESULTS AND DISCUSSION: Median overall survival for imatinib (800 mg/day) and sunitinib both were less than 2 years. Around 25% of patients required either an imatinib dose delay or reduction. Approximately one-third of patients receiving dose escalated imatinib (either dose) showed either response or stable disease. Amongst those responding to the escalated 800 mg/day dose, median progression-free survival was over 25 months. The statistical likelihood of response may depend on exon mutational status. There were few data and those that were available were potentially biased, due to their non-randomised nature. Further data are needed to justify international guideline recommendations on imatinib dose escalation. CONCLUSION: A prospective audit of management and outcomes for unresectable GIST patients treated with dose escalation upon progression at 400 mg/day may be appropriate as an RCT may be unfeasible. PMID- 21971959 TI - Sexual adjustment following early stage cervical and endometrial cancer: prospective controlled multi-centre study. AB - OBJECTIVE: The primary aim of this study was to investigate objective and subjective aspects of sexual adjustment for women with early stage cervical and endometrial cancer during the first 6 months post-treatment, compared to women with benign and pre-invasive gynaecological conditions. 'Objective' aspects of sexual function were operationalised as the frequency of sexual activity and 'subjective' aspects as the perceived quality of sexual interactions. METHOD: This multi-centre controlled study compared sexual outcomes of women treated for early stage cervical and endometrial cancer (n = 53) with (i) benign gynaecological patients (n = 60), as a comparison group for the physical effects of major pelvic surgery, and (ii) pre-invasive cancer patients (n = 52), as a comparison group for the emotional effect of the perceived threat of cancer. All patients were assessed at baseline and at 6 months follow-up using standardised measures of objective and subjective aspects of sexual function, overall satisfaction with sexual life, relationship satisfaction and psychological distress. RESULTS: Despite experiencing treatment-related physical changes, women with early stage cervical and endometrial cancer did not report more severe or longer-lasting sexual sequelae than the benign or pre-invasive groups. There were no significant differences between the three groups or changes over time for the objective, subjective or overall measures of sexual function, controlling for age, psychological distress and relationship satisfaction. CONCLUSION: The current findings suggest that early stage cervical and endometrial cancer patients fare as well as benign and pre-invasive cancer groups in terms of sexual adjustment over the 6 months post-treatment. PMID- 21971960 TI - Interaction of LHBs with C53 promotes hepatocyte mitotic entry: A novel mechanism for HBV-induced hepatocellular carcinoma. AB - The pre-S mutant LHBs, especially the pre-S2 type, is believed to be crucial in HBV-associated hepatocellular carcinogenesis. However, the mechanism of HBV induced hepatocellular carcinoma is not fully understood. To identify the mechanism, pre-S2 LHBs-interacting proteins were studied, by performing a yeast two-hybrid screen of a human liver cDNA library. Screening of the library resulted in the isolation of several positive clones. Sequencing of the positive clones identified the full-length cDNA of the C53 gene. After identification of the interaction, the roles of LHBs on Cdk1, Chk1 activation and mitotic entry were studied. Screening of the library resulted in the isolation of several positive clones, that encoded the full-length cDNA of the C53 gene. We found that C53 interacts with pre-S2 LHBs both in vitro and in vivo, but not with LHBs or other mutants. The binding of pre-S2 LHBs with C53 causes increased Cdk1 activation and mitotic entry, and the function of Chk1 is partially inhibited by the binding of pre-S2 LHBs with C53. Taken together, our results strongly suggest that the binding of pre-S2 LHBs with C53 is a novel negative regulator of the checkpoint response. By counteracting C53, pre-S2 LHBs promotes Cdk1 activation and mitotic entry in unperturbed cell cycle progression and delays the function of Chk1, which may be a novel potential mechanism for HBV-induced hepatocellular carcinoma (HCC). PMID- 21971962 TI - The immune system in neuroendocrine tumors. AB - During the last 30 years the incidence of neuroendocrine tumors has increased considerably and the overall 5-year survival rate has not changed substantially. Conventional therapeutic approaches appear to show an unsatisfactory effect in the more insidious forms of malignancies. Hence, attempts were made to direct the patient's own immune system against cancer by vaccinating against different tumor antigens. Up to date, only sporadic achievements were demonstrated in the majority cases of vaccination trials. One of the main hindrances to a successful vaccination comprises tumor-immune-escape mechanisms. This review focuses on the current knowledge concerning tumor immunoevasion strategies and the immune system in neuroendocrine tumors. PMID- 21971961 TI - Cellular therapy and induced neuronal replacement for Huntington's disease. AB - Huntington's disease (HD) is an inherited, relentlessly progressive neurodegenerative disease with an invariably fatal outcome. HD is inherited in an autosomal dominant fashion, and is characterized pathologically by the loss of cortical and striatal neurons, and clinically by involuntary choreiform movements accompanied by progressive cognitive impairment and emotional lability. The disorder is caused by an expanded cystosine adenine guanine (CAG) tri-nucleotide repeat encoding polyglutamine (polyQ) in the first exon of the Huntingtin gene. There is a correlation between the number of CAG repeats and disease onset, such that in patients with CAG repeat lengths of 36 to 60, disease symptoms typically manifest after 35 years of age, whereas CAG repeat lengths >60 yield the more severe juvenile form of the disease. Even though mutant huntingtin is expressed throughout the brain, it is characterized by the selective degeneration of medium spiny neurons of the caudate and putamen, which heralds more widespread neuronal degeneration with disease progression. The mechanisms of cell dysfunction and death in HD have been the subjects of a number of studies, which have led to therapeutic strategies largely based on the amelioration of mutant huntingtin related metabolic impairment and cellular toxicity. Each of these approaches has aimed to delay or stop the preferential degeneration of medium spiny neurons early in the disease course. Yet, in later stages of the disease, after cell death has become prominent, cell replacement therapy (whether by direct cell transplantation or by the mobilization of endogenous progenitors) may comprise a stronger potential avenue for therapy. In this review, we will consider recent progress in the transplantation of fetal striatal cells to the HD brain, as well as emerging alternative sources for human striatal progenitor cells. We will then consider the potential application of gene therapy toward the induction of striatal neurogenesis and neuronal recruitment, with an eye toward its potential therapeutic use in HD. PMID- 21971963 TI - Movement toward a novel activity monitoring device. AB - PURPOSE: Although polysomnography is necessary for diagnosis of most sleep disorders, it is also expensive, time-consuming, intrusive, and interferes with sleep. Field-based activity monitoring is increasingly used as an alternative measure that can be used to answer certain clinical and research questions. The purpose of this study was to evaluate the reliability and validity of a novel activity monitoring device (Fitbit) compared to both polysomnography and standard actigraphy (Actiwatch-64). METHODS: To test validity, simultaneous Fitbit and actigraph were worn during standard overnight polysomnography by 24 healthy adults at the West Virginia University sleep research laboratory. To test inter Fitbit reliability, three participants also wore two of the Fitbit devices overnight at home. RESULTS: Fitbit showed high intradevice reliability = 96.5 99.1. Fitbit and actigraph differed significantly on recorded total sleep time and sleep efficiency between each other and polysomnography. Bland-Altman plots indicated that both Fitbit and actigraph overestimated sleep efficiency and total sleep time. Sensitivity of both Fitbit and actigraphy for accurately identifying sleep was high within all sleep stages and during arousals; specificity of both Fitbit and actigraph for accurately identifying wake was poor. Specificity of actigraph was higher except for wake before sleep onset; sensitivity of Fitbit was higher in all sleep stages and during arousals. CONCLUSIONS: The web-based Fitbit, available at a markedly reduced price and with several convenience factors compared to standard actigraphy, may be an acceptable activity measurement instrument for use with normative populations. However, Fitbit has the same specificity limitations as actigraphy; both devices consistently misidentify wake as sleep and thus overestimate both sleep time and quality. Use of the Fitbit will also require specific validation before it can be used to assess disordered populations and or different age groups. PMID- 21971964 TI - Near-infrared optical mammography for breast cancer detection with intrinsic contrast. AB - Optical methods to detect breast cancer on the basis of its increased opacity have been explored for some time. These methods have matured to a point in which they are capable of quantifying the optical properties of breast tissue and translating them into measures of concentrations of relevant tissue components. In particular, near-infrared spectroscopy has been employed to determine the concentrations of hemoglobin, water, and lipids, as well as oxygen saturation of hemoglobin and optical scattering properties in normal and cancerous breast tissue. Dynamic optical measurements can also identify abnormal hemodynamic patterns associated with breast cancer. We review, in this article, a number of results in the field, which show that cancerous tissue is associated with higher hemoglobin and water concentrations, and a lower lipid concentration with respect to normal breast tissue. Indications that breast cancers are characterized by lower hemoglobin saturation and stronger scattering decay as a function of wavelength are less robust, with variable results reported in the literature. Intrinsic sources of optical contrast associated with breast cancer can also be used to monitor individual response to neoadjuvant therapy. PMID- 21971965 TI - Vascular wall engineering via femtosecond laser ablation: scaffolds with self containing smooth muscle cell populations. AB - For tissue-engineered vascular grafts to reach their full potential, three dimensional (3D) cellular micro-integration will be necessary. In this study, we utilize femtosecond laser ablation to produce microchannels inside electrospun polycaprolactone (PCL) scaffolds. These microchannels potentially provide spatially controlled cell distributions approaching those observed in vivo. The ability of such laser-ablated microchannels to direct cell seeding was evaluated. The dimensions chosen were 100 MUm wide, 100 MUm deep and 10 mm long. Femtosecond laser ablation successfully produced these microchannels in the scaffolds without substantially altering the ~900 nm diameter fibers. Flow within these microchannels was studied by injecting fluorescent polystyrene bead solutions. Direct measurement of bead motion yielded an inlet velocity of 2.78 cm s(-1). This was used for modeling two-dimensional (2D) flow using computational fluid dynamics to estimate flow profiles within the microchannel. Successful demonstrations of bead flow were followed by seeding of 500,000 human coronary artery smooth muscle cells (HCASMCs) in proliferative medium at a rate of ~500 MUL min(-1). Confocal microscopy and scanning electron microscopy confirmed that the HCASMCs were seeded down the full 10-mm length of the microchannel and stayed within its boundaries. Both nuclei and F-actin were observed within the seeded cells. The presence of F-actin filaments shows that the cells were adhered strongly to the scaffold and remained viable throughout the culture. The concept of "vascular wall engineering" producing intricate cell seeding through microchannels produced via femtosecond laser ablation was validated. PMID- 21971966 TI - Biomechanical impact response of the human chin and manubrium. AB - Chin-to-chest impact commonly occurs in frontal crash simulations with restrained anthropomorphic test devices (ATDs) in non-airbag situations. This study investigated the biofidelity of this contact by evaluating the impact response of both the chin and manubrium of adult post-mortem human subjects (PMHSs). The adult PMHS data were scaled to a 10-year-old (YO) human size and then compared with the Hybrid III 10YO child (HIII-10C) ATD response with the same test configurations. For both the chin and manubrium, the responses of the scaled PMHS had different characteristics than the HIII-10C ATD responses. Elevated energy impact tests to the PMHS mandible provided a mean injury tolerance value for chin impact force. Chin contact forces in the HIII-10C ATD were calculated in previously conducted HYGE sled crash simulation tests, and these contact forces were strongly correlated with the Head Injury Criterion (HIC(36 ms)). The mean injurious force from the PMHS tests corresponded to a HIC(36 ms) value that would predict an elevated injury risk if it is assumed that fractures of the chin and skull are similarly correlated with HIC(36 ms). Given the rarity of same occupant induced chin injury in booster-seated occupants in real crash data and the disparity in chin and manubrium stiffnesses between scaled PMHS and HIII-10C ATD, the data from this study can be made use of to improve biofidelity of chin-to manubrium contact in ATDs. PMID- 21971967 TI - Diversity and phylogeny of the ectoine biosynthesis genes in aerobic, moderately halophilic methylotrophic bacteria. AB - The genes of ectoine biosynthesis pathway were identified in six species of aerobic, slightly halophilic bacteria utilizing methane, methanol or methylamine. Two types of ectoine gene cluster organization were revealed in the methylotrophs. The gene cluster ectABC coding for diaminobutyric acid (DABA) acetyltransferase (EctA), DABA aminotransferase (EctB) and ectoine synthase (EctC) was found in methanotrophs Methylobacter marinus 7C and Methylomicrobium kenyense AMO1(T). In methanotroph Methylomicrobium alcaliphilum ML1, methanol utilizers Methylophaga thalassica 33146(T) , Methylophaga alcalica M8 and methylamine-utilizer Methylarcula marina h1(T), the genes forming the ectABC-ask operon are preceded by ectR, encoding a putative transcriptional regulatory protein EctR. Phylogenetic relationships of the Ect proteins do not correlate with phylogenetic affiliation of the strains, thus implying that the ability of methylotrophs to produce ectoine is most likely the result of a horizontal transfer event. PMID- 21971968 TI - Comparison of different neuron models to conductance-based post-stimulus time histograms obtained in cortical pyramidal cells using dynamic-clamp in vitro. AB - A wide diversity of models have been proposed to account for the spiking response of central neurons, from the integrate-and-fire (IF) model and its quadratic and exponential variants, to multiple-variable models such as the Izhikevich (IZ) model and the well-known Hodgkin-Huxley (HH) type models. Such models can capture different aspects of the spiking response of neurons, but there is few objective comparison of their performance. In this article, we provide such a comparison in the context of well-defined stimulation protocols, including, for each cell, DC stimulation, and a series of excitatory conductance injections, arising in the presence of synaptic background activity. We use the dynamic-clamp technique to characterize the response of regular-spiking neurons from guinea-pig visual cortex by computing families of post-stimulus time histograms (PSTH), for different stimulus intensities, and for two different background activities (low- and high-conductance states). The data obtained are then used to fit different classes of models such as the IF, IZ, or HH types, which are constrained by the whole data set. This analysis shows that HH models are generally more accurate to fit the series of experimental PSTH, but their performance is almost equaled by much simpler models, such as the exponential or pulse-based IF models. Similar conclusions were also reached by performing partial fitting of the data, and examining the ability of different models to predict responses that were not used for the fitting. Although such results must be qualified by using more sophisticated stimulation protocols, they suggest that nonlinear IF models can capture surprisingly well the response of cortical regular-spiking neurons and appear as useful candidates for network simulations with conductance-based synaptic interactions. PMID- 21971969 TI - Involvement of activation of toll-like receptors and nucleotide-binding oligomerization domain-like receptors in enhanced IgG4 responses in autoimmune pancreatitis. AB - OBJECTIVE: IgG4-related disease is a recently recognized entity affecting multiple organs, including the pancreas, biliary tracts, and salivary glands. Although IgG4-related disease is characterized by systemic IgG4 antibody responses and by infiltration of IgG4-expressing plasma cells, the innate immune responses leading to adaptive IgG4 antibody responses are poorly understood. The aim of this study was to clarify the innate immune responses leading to IgG4 antibody production. METHODS: IgG4 and cytokine responses to various nucleotide binding oligomerization domain (NOD)-like receptor (NLR) and Toll-like receptor (TLR) ligands were examined using peripheral blood mononuclear cells (PBMCs) from healthy control subjects and patients with IgG4-related autoimmune pancreatitis. RESULTS: Activation of NOD-2 in monocytes from healthy control subjects induced IgG4 production by B cells in a BAFF-dependent and T cell-independent manner. In addition, PBMCs from patients with IgG4-related disease produced a large amount of IgG4 upon stimulation with NLR and TLR ligands; this enhanced IgG4 production was associated with the induction of BAFF by NLR and TLR ligands. Monocytes from patients with IgG4-related disease induced IgG4 production by B cells from healthy control subjects upon stimulation with NLR and TLR ligands. CONCLUSION: The results of these studies suggest that abnormal innate immune responses against microbial antigens may underlie the immunopathogenesis of IgG4-related disease. PMID- 21971970 TI - Effects of acute exposure to exogenous ammonia on cerebral monoaminergic neurotransmitters in juvenile Solea senegalensis. AB - The present study explored the potential role of brain catecholaminergic and serotoninergic systems as neuronal targets for the toxicological effects of acute ammonia exposure (0.28 mg l(-1) of un-ionized ammonia for 12 and 24 h) in juvenile sole (Solea senegalensis). In addition, plasma cortisol levels were measured. The results showed significant increases in their concentrations that were similar after 12 and 24 h of exposure. These data indicate that acute exposure (12 and 24 h) to ammonia initiates a typical stress response in the Senegalese sole, with stimulation of the hypothalamus-pituitary-interrenal axis. The concentrations of dopamine (DA), serotonin (5-hydroxytryptamine; 5-HT) and noradrenaline (NA), and their metabolites, 3, 4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxy-3-indoleacetic acid (5HIAA), were measured in the hypothalamus, telencephalon and optic tectum. The main changes induced by acute exposure to ammonia were decreases in the concentrations of 5-HT and DA, which were significant in most of the brain regions studied. The ratios of 5-HIAA/5-HT and DOPAC/DA increased in all regions and at all times studied, although in the case of the DOPAC/DA ratio, the increases were only significant in the hypothalamus (24 h exposure) and in the optic tectum (12 and 24 h exposure). These changes indicated that exposure to ammonia elicited time-dependent increases in serotoninergic and dopaminergic activity in the hypothalamus, telencephalon and optic tectum. PMID- 21971971 TI - Sub-lethal effects induced by a mixture of three non-steroidal anti-inflammatory drugs (NSAIDs) on the freshwater bivalve Dreissena polymorpha. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are the sixth top-selling drugs worldwide and are commonly found in freshwater ecosystems in the high ng/l to low MUg/l range. Recent studies have investigated both the acute and the chronic toxicity of single NSAIDs on different biological models, but these studies have completely neglected the fact that, in the environment, non-target organisms are exposed to mixtures of drugs that have unforeseeable toxicological behavior. This work investigated the sub-lethal effects induced by a mixture of three common NSAIDs, namely, diclofenac, ibuprofen and paracetamol, on the freshwater bivalve, the zebra mussel (Dreissena polymorpha). The mussels were exposed to three different environmental concentrations of the mixture (Low, Mid and High). A multi-biomarker approach was used to highlight cyto-genotoxic effects and the imbalance of the oxidative status of the treated specimens. The Neutral Red Retention Assay (NRRA) was used as a biomarker of cytotoxicity, whereas the activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione S-transferase were measured to assess the role played by the oxidative stress enzymes. In addition, the single cell gel electrophoresis assay, the DNA Diffusion assay and the micronucleus test were used to investigate possible genotoxic effects. According to our NRRA results, each treatment was able to induce a significant cellular stress in bivalves, probably due to the raise of oxidative stress, as indicated by the alteration of enzyme activities measured in treated specimens. Moreover, the mixture induced significant enhancements of DNA fragmentation, which preluded fixed genetic damage, as highlighted by the increase of both apoptotic and micronucleated cells. PMID- 21971972 TI - Flow cytometric analysis to evaluate physiological alterations in herbicide exposed Chlamydomonas moewusii cells. AB - Investigation of herbicide toxicology in non-target aquatic primary producers such as microalgae is of great importance from an ecological point of view. In order to study the toxicity of the widely used herbicide paraquat on freshwater green microalga Chlamydomonas moewusii, physiological changes associated with 96 h-exposures to this pollutant were monitored using flow cytometry (FCM) technique. Intracellular reactive oxygen species concentration, cytoplasmic membrane potential, metabolic activity and cell protein content were monitored to evaluate the toxicological impact of paraquat on algal physiology. Results showed that herbicide paraquat induced oxidative stress in C. moewusii cells, as it indicated the increase of both superoxide anion and hydrogen peroxide levels observed in non-chlorotic cells of cultures exposed to increasing herbicide concentrations. Furthermore, a progressive increase in the percentage of depolarised cells and a decrease in the metabolic activity level were observed in response to paraquat when non-chlorotic cells were analysed. Chlorotic cells were probably non-viable cells, based on the cytoplasmic membrane depolarisation, its metabolically non-active state and its drastically reduced protein content. In view of the obtained results, we have concluded that a range of significant physiological alterations, detected by flow cytometry, occur when C. moewusii, an ubiquitous microalga in freshwater environments, is challenged with environmentally relevant concentrations of the herbicide paraquat. PMID- 21971973 TI - Differences in susceptibility of five cladoceran species to two systemic insecticides, imidacloprid and fipronil. AB - Differences in susceptibility of five cladocerans to the neonicotinoid imidacloprid and the phenyl-pyrazole fipronil, which have been dominantly used in rice fields of Japan in recent years, were examined based on short-term (48-h), semi-static acute immobilization exposure tests. Additionally, we compared the species sensitivity distribution (SSD) patterns of both insecticides between two sets of species: the five tested cladocerans and all other aquatic organisms tested so far, using data from the ECOTOX database of U.S. Environmental Protection Agency (USEPA). The sensitivity of the test species to either imidacloprid or fipronil was consistent, spanning similar orders of magnitude (100 times). At the genus level, sensitivities to both insecticides were in the following descending order: Ceriodaphnia > Moina > Daphnia. A positive relationship was found between body lengths of each species and the acute toxicity (EC(50)) of the insecticides, in particular fipronil. Differences in SSD patterns of imidacloprid were found between the species groups compared, indicating that test cladocerans are much less susceptible than other aquatic species including amphibians, crustaceans, fish, insects, mollusks and worms. However, the SSD patterns for fipronil indicate no difference in sensitivity between cladocerans tested and other aquatic organisms despite the greater exposure, which overestimates the results, of our semi-static tests. From these results, Ceriodaphnia sp. should be considered as more sensitive bioindicators (instead of the standard Daphnia magna) for ecotoxicological assessments of aquatic ecosystems. In addition, we propose that ecotoxicity data associated with differences in susceptibility among species should be investigated whenever pesticides have different physicochemical properties and mode of action. PMID- 21971974 TI - Remote monitoring of heart failure patients using implantable cardiac pacing devices and external sensors: results of the Insight-HF study. AB - AIM: The rapidly increasing prevalence and poor outcome of congestive heart failure have stimulated the development of different telemonitoring technologies. In this study, we monitored remotely self-measured body weight and blood pressure, in parallel with the data automatically transmitted by implantable cardioverter-defibrillators. The primary aim of this study was to evaluate the correlation between different parameters screened by these two telemonitoring systems. METHODS AND RESULTS: Thirty-two patients in NYHA class III heart failure were followed for 164 +/- 48 days after cardioverter-defibrillator implantation. In 29 patients, mean heart rate (MHR), resting heart rate (RHR), and patient activity (determined by implanted devices), weight and blood pressure measurements were received on 85% of all days when remote data transmissions were expected. Based on approximately 4,000 daily pairs of measurements pooled for all patients, weight inversely correlated with activity and with the difference between MHR and RHR. By contrast, blood pressure did not correlate with weight, activity, or the difference between MHR and RHR, but it correlated with MHR and RHR individually. CONCLUSION: Body weight, patient activity, and the difference between MHR and RHR are mutually correlated and may reasonably contribute to an algorithm for predicting heart failure deterioration. Blood pressure appears to offer no additional value. As both genesis and symptoms of heart failure exacerbation are non-uniform and complex, the telemonitoring concepts for heart failure patients should employ continuous monitoring of multiple diagnostic parameters, rather than rely on a single parameter. Provided that patient compliance is strictly supervised, reliable data flow from sensors requiring patient involvement is possible. PMID- 21971976 TI - Up-regulation of TGF-beta via the activation of extracellular signal-regulated kinase 1 and 2 induced by prorenin in human renal mesangial cells. AB - Prorenin is thought to be an inactive precursor of renin. This study investigated whether human prorenin was capable of activating the (pro)renin receptors [(P)RRs], leading to the phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) in cultured human renal mesangial cells (HRMCs). HRMCs cultured in vitro were pretreated with an AT1 and AT2 blocker prior to stimulation by prorenin, PD98059 (an inhibitor of ERK1/2) and handle-region peptide (HRP). Phosphorylated ERK1/2 was evaluated using Western blot analysis, and the concentration of TGF-beta was measured by ELISA. The mRNA of TGF-beta was evaluated by RT-PCR. It was found that prorenin activated the (P)RR in cultured HRMCs, which in turn increased p-ERK1/2. Prorenin induced rapid phosphorylation of ERK1/2 and increased p-ERK1/2 in a time- and dose-dependent manner. The protein levels of TGF-beta increased significantly with the stimulation of prorenin. PD98059 significantly decreased p-ERK1/2 and then downregulated TGF beta. HRP did not inhibit either ERK1/2 phosphorylation or the increase in TGF beta. ERK1/2 phosphorylation induced by prorenin led to a marked increase in TGF beta. The regulation of TGF-beta was highly dependent on ERK1/2. Thus, ERK1/2 may play a key role in the development of kidney disease. HRP neither affects the ERK1/2 signaling nor the level of TGF-beta in HRMCs. PMID- 21971977 TI - What goes up does not always come down: patterns of distress, physical and psychosocial morbidity in people with cancer over a one year period. AB - BACKGROUND: As the concept of distress as the 6th vital sign gains strength in cancer care, research on the experience of patients is critical. This study longitudinally examined patients' physical and psychosocial concerns over the year following diagnosis. METHODS: Between July 2007 and February 2008, patients attending a large tertiary cancer centre were recruited to participate in a study examining their levels of distress, pain, fatigue, depression and anxiety over a year. RESULTS: A total of 877 patients provided baseline data with 620, 589 and 505 retained at 3, 6 and 12 months, respectively. Overall, levels of distress, depression and anxiety decreased significantly over the study period. No significant changes were found in levels of pain or fatigue. Demographics (being unmarried) and medical interventions (particularly having radiation therapy) predicted persistent distress, anxiety and depression, whereas receiving psychosocial support predicted decreased levels of distress, anxiety and depression. Some patients reported continued clinical levels of distress (29%), pain (19%) and fatigue (40%) 12 months post diagnosis. DISCUSSION: For some people, distress, depression, and anxiety may be transient and decrease over time, but for others they may be sustained. Pain and fatigue may remain present in many cancer patients. There is a need to modify current clinical practice to facilitate the appropriate assessment and management of distress. PMID- 21971978 TI - Clinical phenomenology and neuroimaging correlates in ALS-FTD. AB - The overlap of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) has been well documented in FTD patients with co-morbid motor neuron degeneration and in ALS patients with frontotemporal dysfunction. Up to 15% of FTD patients and 30% of ALS patients experience the overlap syndrome. The syndrome may be difficult to identify since patients often present either to a neuromuscular clinic or a memory disorder's center, each which may have limited expertise in the other specialty. Survival is greatly impacted for both disorders in the co-morbid condition, making identification of this syndrome critical. The clinical characteristics of the overlap syndrome with new diagnostic criteria will be discussed along with screening strategies, including the UCSF Screening battery and clinical neurophysiology techniques. Treatable mimics of this disorder will also be described and management techniques. Neuroimaging findings will be summarized, which show that the frontotemporal impairment in ALS patients lies on a continuum. Identification of the overlap syndrome also provides a unique opportunity to study very early signs of FTD and conversely, very early signs of ALS, to gain greater insight into both disorders. PMID- 21971979 TI - Quaternary centres as a tool for modulating foldamer conformation. PMID- 21971980 TI - Efficient delivery of gold nanoparticles by dual receptor targeting. PMID- 21971982 TI - Support, opinion of support and psychological health among survivors of a natural disaster. AB - BACKGROUND: Although formal intervention after disasters is recommended, the evidence base for this is weak. Satisfaction with support after disasters is seldom investigated and the relation to psychological symptoms is unknown. AIMS: To investigate whether dissatisfaction with social and formalized support are associated with post-disaster psychological symptoms. METHODS: A total of 1,505 Swedish survivors of the 2004 Indian Ocean tsunami responded to a questionnaire 14 months after the disaster, including the General Health Questionnaire-12, the Impact of Events Scale - Revised, the Crisis Support Scale, and questions concerning the reception and appraisal of social and formalized support from health care, psychological services and insurance agencies. Disaster exposure and background factors were controlled for in the analyses. RESULTS: Reception of formalized support, but not social support, was associated with both psychological distress and post-traumatic stress. Dissatisfaction with social but not formalized support, with the exception of support from insurance agencies, was associated with psychological distress. CONCLUSIONS: Social support and formalized support should be differentiated in future studies in order to improve preventive intervention efforts after disasters. The reporting of dissatisfaction with social support merits special attention, since this may indicate increased risk for psychological symptoms. PMID- 21971981 TI - Empowering caregivers: impact analysis of FamilyLink Education Programme (FLEP) in Hong Kong, Taipei and Bangkok. AB - BACKGROUND: Education and support for caregivers is lacking in Asia and the peer led FamilyLink Education Programme (FLEP) is one of the few provisions to address this service gap. This study aims to evaluate quantitatively its efficacy in reducing subjective burdens and empowering the participants. METHOD: One hundred and nine caregiver participants in three Asian cities were successfully surveyed at pre-intervention, post-intervention and six-month intervals with a number of standard inventories. Mixed analysis of variance (ANOVA) procedures showed significant programme impact over time intervals for all sites, and subsequently an empowerment measurement model was tested. RESULTS: FLEP was found effective in reducing worry and displeasure, significantly improving intra-psychic strain, depression and all empowerment measures. The measurement model had an acceptable good fit. Baseline difference showed no interference with the programme efficacy. CONCLUSIONS: Apart from the initial support for FLEP, the current study also provides some hindsight on the empowerment practice in mental health for Asia, whose sociocultural political contexts are vastly different from that of the developed countries. It remains to be seen whether qualitative data or more stringent research design will yield consistent results and whether FLEP can also work in rural areas. PMID- 21971983 TI - Early adult outcomes for Irish children with behavioural difficulties. AB - BACKGROUND: There are few longitudinal studies of Irish children and, to date, no studies reporting long-term outcome for those with behavioural disorder in childhood. This paper describes psychological and educational outcomes for a group of Irish children initially assessed at age 11 years and re-examined 10 years later. The period during which the research was conducted coincided with a time of increasing wealth in Ireland and the consequent development of psychological and educational services. AIMS: To follow up and assess psychological and educational outcomes for a group of young people aged 21 years, half of whom had high levels of behavioural problems at age 11. METHOD: Data were gathered at two time points for 97 children and their families. Childhood measures included psychological and behavioural functioning, IQ, family background and economic circumstances. Outcome measures assessed in young adulthood included psychological functioning, educational attainment and trouble with the law. RESULTS: Behavioural deviance at age 11 was found to be highly predictive of negative outcomes in early adulthood including a greater likelihood of involvement in criminal activity and less educational success. The likelihood of educational failure increased with the accumulation of risk factors including economic disadvantage and low IQ. CONCLUSIONS: These findings, supported in other international studies, underline the importance of behavioural difficulties in childhood for adult outcome, even in an environment of greater service and educational opportunities and access. PMID- 21971984 TI - Typology of schizophrenic symptoms and quality of life in patients and their main caregivers in northern Chile. AB - BACKGROUND: Schizophrenia is a serious mental disorder characterized by the presence of both 'positive' and 'negative' symptoms that affect the essential functions through which a person gains his or her sense of individuality and capacity for independent functioning. AIMS: To describe the typology of schizophrenic symptoms and their relationship to quality of life in patients with schizophrenia and their main caregivers. METHODS: Participants were 45 patients and 45 relatives seen by the mental health services in Arica, Chile. Patients were assessed using the Positive and Negative Syndrome Scale (PANSS), the Seville Quality of Life Questionnaire (SQLQ), and the Social Functioning Scale (SFS). The latter was also administered to caregivers, along with the Zarit Burden Interview. RESULTS: Patients reported moderate levels of quality of life, there being a strong relationship with the negative syndrome and the general psychopathology of the disorder. The quality of life of main caregivers was related with the general psychopathology of patients. The results regarding social functioning and the caregivers' perceptions of patients' functional capacity showed that patients had a very limited degree of social integration. CONCLUSIONS: Negative symptoms and general psychopathology are the main predictors of quality of life in both patients and their caregivers. PMID- 21971986 TI - The value of biomedical research training for veterinary anatomic and clinical pathologists. AB - Veterinary pathologists traditionally have been actively engaged in research as principal investigators and as collaborators. Pathologists frequently obtain advanced training in research; however, it appears that in the last 10 years there has been a reversal of a previous trend toward increasing numbers of pathologists obtaining PhD degrees. This has arisen despite an established shortage of veterinarians engaged in research. This article evaluates the benefits of research training for individual pathologists, including a wide spectrum of professional opportunities and additional skill development beyond that usually provided by diagnostic pathology training alone. Various training models are discussed, including combined and sequential diagnostic residency and research degree training as well as the nondegree research fellowship programs more commonly pursued in human medicine. Best-practice recommendations for program infrastructure, mentorship, time management, and a team approach to research and research training are advocated to facilitate the development of successful programs and to encourage a continued emphasis on integrated training for pathologists as both clinical diagnosticians and experimentalists. This article is intended to help prospective and active pathology trainees, their mentors, and educational administrators optimize opportunities to ensure the future vitality of veterinary pathologists, and their contributions, in basic and applied research. PMID- 21971985 TI - S100A8-targeting siRNA enhances arsenic trioxide-induced myeloid leukemia cell death by down-regulating autophagy. AB - Chemoresistance has become a major obstacle to the successful treatment of leukemia. Autophagy, a regulated process of degradation and recycling of cellular constituents, has recently caught increasing attention for its roles in conferring resistance to various commonly used anticancer therapies. Here we showed that the member of the S100 calcium-binding protein family, S100A8, is a critical regulator of chemoresistance in the autophagy process. It positively correlated with the clinical status in childhood acute myeloblastic leukemia (AML) and it was released from leukemia cells after chemotherapy-induced cytotoxicity. Knockdown of S100A8 expression increased the sensitivity of leukemia cells to chemotherapy and apoptosis. Moreover, suppressing S100A8 expression decreased autophagy as evaluated by the increased expression of the autophagic marker microtubule-associated protein light chain 3 (LC3)-II, degradation of SQSTM1/Sequestosome 1 (p62) and formation of autophagosomes. Furthermore, stimuli that enhanced reactive oxygen species (ROS) promoted cytosolic translocation of S100A8 and thereby enhanced autophagy. S100A8 directly interacted with the autophagy protein Beclin1 displacing Bcl-2. These results suggest that S100A8 is a critical pro-autophagic protein that enhances cell survival and regulates chemoresistance in leukemia cells likely through disassociating the Beclin1-Bcl-2 complex. PMID- 21971987 TI - The gene or not the gene--that is the question: understanding the genetically engineered mouse phenotype. AB - Embryonic stem cells have had a significant impact on understanding gene function and gene interactions through the use of genetically engineered mice. However, the genetic context (ie, mouse strain) in which these modifications in alleles are made may have a considerable effect on the phenotypic changes identified in these mice. In addition, tissue- and time-specific gene expression systems may generate unanticipated outcomes. This article discusses the history of embryonic stem cells, reviews how mouse strain can affect phenotype (using specific examples), and examines some of the caveats of conditional gene expression systems. PMID- 21971988 TI - Enzymatic enantiomeric resolution of phenylethylamines structurally related to amphetamine. AB - Both enantiomers of several phenylethylamines, structurally related to amphetamine, have been prepared in good yields and excellent enantiomeric purity by enzymatic kinetic resolution using CAL-B and ethyl methoxyacetate as the acyl donor. In the case of the 4-hydroxyderivative of amphetamine (compound 4i), the S enantiomer racemized possibly in a dynamic kinetic resolution (DKR) under the enzymatic conditions used. PMID- 21971989 TI - Functional expression and characterization in Xenopus laevis oocytes of the ABCG2 transporter derived from A549 human lung adenocarcinoma cells. AB - We cloned the ATP-binding cassette sub-family G member 2 (ABCG2) transporter, the most recently identified among several major human multidrug-resistance pumps, from A549 human lung adenocarcinoma cells in order to characterize its function and substrate specificity. In a previous report, we confirmed that a stem cell like side population of A549 cells highly expressed the ABCG2 gene and had a unique ability to resist the anticancer drug methotrexate (MTX). In this study, ABCG2 cDNA was cloned by RT-PCR and converted into cRNA by an in vitro transcription system for expression in Xenopus laevis (X. laevis) oocytes. The transcribed cRNA of the ABCG2 gene was injected into the oocytes under the absence of cofactors or heterologous partner proteins or some lipids from the media. A high expression of ABCG2 was observed on the oocyte surface by immunofluorescence and confocal laser microscopy. We tested the functional effect of ABCG2 expression on drug efflux by directly injecting MTX into X. laevis oocytes. The drug concentration within the oocytes was quantified with LC-MS/MS; the analysis showed that the accumulation of MTX was significantly decreased in the X. laevis oocytes expressing ABCG2 compared with the control oocytes not expressing ABCG2. These findings show that the ABCG2 protein has an important role in the efflux of MTX through the cell membrane of X. laevis oocytes. Therefore, it might be that ABCG2, abundantly expressed in the stem cell population of A549 cells, can modulate resistance to MTX in lung cancer therapy. PMID- 21971990 TI - The structure, properties, and nature of unconventional pi halogen bond in the complexes of Al4(2-) and halohydrocarbons. AB - Quantum chemical calculations have been performed to study the all-metal pi halogen bonding in Al(4)(2-)...halohydrocarbon complexes. The result shows the existence of the all-metal pi halogen bond in the complexes. There are three interaction modes (top, corner, and side) between Al(4)(2-) and halohydrocarbon. The interaction energy of this interaction varies from a positive value to -90.54 kJ mol(-1) in Al(4)(2-)...I-ethyne-s complex. The interaction strength is affected greatly by the hybridization of C atom and follows the order of C(sp(3)) < C(sp(2)) < C(sp) in most complexes. The methyl group in the halogen donor plays a negative contribution to the formation of halogen bond. The halogen bonding becomes stronger for the heavier halogen atom. The effect of binding site on the strength of halogen bond is related with the nature of halogen atom. The complexes have been analyzed with electrostatic potential, NICS, ELF, NBO, and AIM. PMID- 21971991 TI - Genomic diversity of Ac-like transposable elements in sphaerococcum mutant forms of common wheat (Triticum aestivum L.) and triticale (X Triticosecale Witt.). AB - DNA sequences homologous to the maize Activator (Ac) element are widespread in plant genomes. Nowadays, several reports are available concerning the distribution and characterisation of Ac-homologous sequences in natural populations of different cereal species. but these mobile genetic elements still remain to be comprehensively characterised. In this respect, there is a particular lack of information about the dynamics of Ac-homologous sequences within mutant germplasm collections. Here, we present data on the genomic diversity and methylation patterns of Ac-homologous sequences in ethyl methanesulphonate (EMS)-induced sphaerococcum mutant forms of common wheat (Triticum aestivum L.) and triticale (X Triticosecale Witt.). The results show that the initial EMS treatment has influenced the wheat genome stability by enhancing the dynamics of Ac transposon-homologous sequences. PMID- 21971992 TI - The type I interferon response during viral infections: a "SWOT" analysis. AB - The type I interferon (IFN) response is a strong and crucial moderator for the control of viral infections. The strength of this system is illustrated by the fact that, despite some temporary discomfort like a common cold or diarrhea, most viral infections will not cause major harm to the healthy immunocompetent host. To achieve this, the immune system is equipped with a wide array of pattern recognition receptors and the subsequent coordinated type I IFN response orchestrated by plasmacytoid dendritic cells (pDCs) and conventional dendritic cells (cDCs). The production of type I IFN subtypes by dendritic cells (DCs), but also other cells is crucial for the execution of many antiviral processes. Despite this coordinated response, morbidity and mortality are still common in viral disease due to the ability of viruses to exploit the weaknesses of the immune system. Viruses successfully evade immunity and infection can result in aberrant immune responses. However, these weaknesses also open opportunities for improvement via clinical interventions as can be seen in current vaccination and antiviral treatment programs. The application of IFNs, Toll-like receptor ligands, DCs, and antiviral proteins is now being investigated to further limit viral infections. Unfortunately, a common threat during stimulation of immunity is the possible initiation or aggravation of autoimmunity. Also the translation from animal models to the human situation remains difficult. With a Strengths Weaknesses-Opportunities-Threats ("SWOT") analysis, we discuss the interaction between host and virus as well as (future) therapeutic options, related to the type I IFN system. PMID- 21971993 TI - The themes, institutions, and people of medical education research 1988-2010: content analysis of abstracts from six journals. AB - The present study aimed at providing an overview of the most common themes of research into medical education. Changes in frequency of occurrence of these themes over time and differences between US and European journals were studied. The most productive institutions and researchers in the field were examined. A content analysis was carried out on 10,168 abstracts extracted from the six most influential journals in medical education published since 1988. Twenty-nine major themes were identified, of which student assessment, clinical and communication skills, clinical clerkships, and problem-based learning were the most prominent ones. Some of these themes, such as multiple-choice examinations or computer assisted instruction seemed to have had their day, whereas other topics, such as the study of clinical clerkships, clinical reasoning, and scholarship in education were on their way up. Medical education research turned out to be a thoroughly international affair to which both US and European research centers contribute. The medical education literature shows an overwhelming emphasis on the preparation of medical students for professional practice. Moreover, the emphasis is very much on the individual student; most research seems to have been conducted with a psychological perspective in mind. It is argued that medical education research would profit from broadening its scope, including sociological, economical, ecological, and system perspectives. These perspectives might bring answers to new questions relevant to the quality of medical education. It is suggested that medical education is in need of moving beyond the conventional effectiveness-driven research approach to a more theory- and discovery-driven approach. PMID- 21971994 TI - An ER-targeted calcium-binding peptide confers salt and drought tolerance mediated by CIPK6 in Arabidopsis. AB - Different plant organelles have high internal stores of Ca(2+) compared to the cytoplasm and could play independent roles in stress responses or signal transduction. We used a GFP fusion with the C-domain of calreticulin, which shows low-affinity, high capacity Ca(2+) binding in the ER, as a calcium-binding peptide (CBP) to specifically increase stores in the ER and nucleus. Despite the presence of a signal sequence and KDEL retention sequence, our work and previous studies (Brandizzi et al. Plant Journal 34:269-281, 2003) demonstrated both ER and nuclear localization of GFP-CBP. Under normal conditions, GFP-CBP-expressing lines had ~25% more total Ca(2+) and higher levels of chlorophyll and seed yield than wild type and GFP controls. CBP-expressing plants also had better survival under intermittent drought or high salt treatments and increased root growth. One member of the CIPK (calcineurin B-like interacting protein kinase) gene family, CIPK6, was up-regulated in CBP-expressing plants, even under non-stress conditions. A null mutation in cipk6 abolished the increased stress tolerance of CBP-transgenic plants, as well as the CBP-mediated induction of two stress associated genes, DREB1A and RD29A, under non-stress conditions. Although this suggested that it was the induction of CIPK6, rather than localized changes in Ca(2+), that resulted in increased survival under adverse conditions, CIPK6 induction still required Ca(2+). This work demonstrates that ER (or nuclear) Ca(2+) can directly participate in signal transduction to alter gene expression. The discovery of a method for increasing Ca(2+) levels without deleterious effects on plant growth may have practical applications. PMID- 21971997 TI - Clinical images: Multilocular tenosynovitis as a manifestation of sarcoidosis. PMID- 21971995 TI - Expression of the nucleocapsid protein of porcine reproductive and respiratory syndrome virus in soybean seed yields an immunogenic antigenic protein. AB - Porcine reproductive and respiratory syndrome (PRRS), caused by the PRRS virus (PRRSV), is a serious disease of swine and contributes to severe worldwide economic losses in swine production. Current vaccines against PRRS rely on the use of an attenuated-live virus; however, these are unreliable. Thus, alternative effective vaccines against PRRS are needed. Plant-based subunit vaccines offer viable, safe, and environmentally friendly alternatives to conventional vaccines. In this study, efforts have been undertaken to develop a soybean-based vaccine against PRRSV. A construct carrying a synthesized PRRSV-ORF7 antigen, nucleocapsid N protein of PRRSV, has been introduced into soybean, Glycine max (L.) Merrill. cvs. Jack and Kunitz, using Agrobacterium-mediated transformation. Transgenic plants carrying the sORF7 transgene have been successfully generated. Molecular analyses of T(0) plants confirmed integration of the transgene and transcription of the PRRSV-ORF7. Presence of a 15-kDa protein in seeds of T(1) transgenic lines was confirmed by Western blot analysis using PRRSV-ORF7 antisera. The amount of the antigenic protein accumulating in seeds of these transgenic lines was up to 0.65% of the total soluble protein (TSP). A significant induction of a specific immune response, both humoral and mucosal, against PRRSV-ORF7 was observed following intragastric immunization of BALB/c female mice with transgenic soybean seeds. These findings provide a 'proof of concept', and serve as a critical step in the development of a subunit plant based vaccine against PRRS. PMID- 21971996 TI - Overexpression of Nelumbo nucifera metallothioneins 2a and 3 enhances seed germination vigor in Arabidopsis. AB - Metallothioneins (MTs) are small, cysteine-rich and metal-binding proteins which are involved in metal homeostasis and scavenging of reactive oxygen species. Although plant MTs have been intensively studied, their roles in seeds remain to be clearly established. Here, we report the isolation and characterization of NnMT2a, NnMT2b and NnMT3 from sacred lotus (Nelumbo nucifera Gaertn.) and their roles in seed germination vigor. The transcripts of NnMT2a, NnMT2b and NnMT3 were highly expressed in developing and germinating sacred lotus seeds, and were dramatically up-regulated in response to high salinity, oxidative stresses and heavy metals. Analysis of transformed Arabidopsis protoplasts showed that NnMT2a YFP and NnMT3-YFP were localized in cytoplasm and nucleoplasm. Transgenic Arabidopsis seeds overexpressing NnMT2a and NnMT3 displayed improved resistance to accelerated aging (AA) treatment, indicating their significant roles in seed germination vigor. These transgenic seeds also exhibited higher superoxide dismutase activity compared to wild-type seeds after AA treatment. In addition, we showed that NnMT2a and NnMT3 conferred improved germination ability to NaCl and methyl viologen on transgenic Arabidopsis seeds. Taken together, these data demonstrate that overexpression of NnMT2a and NnMT3 in Arabidopsis significantly enhances seed germination vigor after AA treatment and under abiotic stresses. PMID- 21971998 TI - ralpha Structures of partially oriented pentafluorobenzenes C6F5X (X = H, Cl, I) as determined from 19F NMR spectra with 13C satellites. AB - The (19)F spectra with natural-abundance carbon-13 satellites of C(6)F(5)X (X = H, Cl or I) in ZLI 1695 liquid crystal were analysed. Excluding fluorine-fluorine dipolar coupling constants from the fitting, the vibrationally corrected structures of these molecules were derived and compared with those calculated at DFT/B3LYP level of theory with the aug-cc-pVTZ basis set. The results show that pentafluorobenzene did not exhibit noticeable distortion of the aromatic ring, while chloropentafluorobenzene and iodopentafluorobenzene molecules showed some deformations in their determined structures. Relative anisotropies of F-F couplings have been deduced with accuracy for C(6)F(5)H molecule. Due to uncertainties in structure determination of C(6)F(5)Cl and C(6)F(5)I molecules, it was not possible to obtain precise values for all the corresponding anisotropies. In addition, it was found that the orientation of these molecules in the solvent used can be qualitatively explained in terms of dispersion forces. PMID- 21972000 TI - Posttraumatic growth, social support, and social constraint in hematopoietic stem cell transplant survivors. AB - OBJECTIVE: The relation between posttraumatic growth (PTG) and aspects of the social context, such as social support and social constraint, continues to be unclear in cancer survivors. Social cognitive processing theory is a useful framework for examining the effect of the social context on PTG. In theory, support interactions may either facilitate or hinder cognitive processing and thus lead to different PTG outcomes. The current study tested the hypothesis that emotional support and instrumental support would each explain a unique amount of the variance in PTG in distressed hematopoietic stem cell transplant (HSCT) survivors. Additionally, it was predicted that social constraint on cancer related disclosure would be negatively associated with PTG. METHODS: Forty-nine distressed HSCT survivors with a spouse or partner completed the posttraumatic growth inventory and measures of social support received from their spouse/partner and social constraint from people close to them as part of a larger clinical trial. RESULTS: Both emotional and instrumental social support were positively correlated with PTG, and social constraint on disclosure was not associated with PTG. Contrary to hypotheses, instrumental support was the only unique social contextual predictor of PTG. CONCLUSIONS: The results of this study highlight the importance of examining the effects of subtypes of social support on PTG separately. Findings are discussed in the context of the cognitive (i.e., processing of the traumatic event) versus non-cognitive (i.e., buffering stress) pathways between the social context and PTG. Future research directions are presented. PMID- 21972002 TI - Gold(I) and gold(III) corroles. AB - Corrole complexes with gold(I) and gold(III) were synthesized and their structural, photophysical, and electrochemical properties investigated. This work includes the X-ray crystallography characterization of gold(I) and gold(III) complexes, both chelated by a corrole with fully brominated beta-pyrrole carbon atoms. The mononuclear and chiral gold(I) corrole appears to be the first of its kind within the porphyrinoid family, while the most unique property of the gold(III) corrole is that it displays phosphorescence at ambient temperatures. PMID- 21971999 TI - Psychological stress and aging: role of glucocorticoids (GCs). AB - Psychological stress has extreme adverse consequences on health. However, the molecular mechanisms that mediate and accelerate the process of aging due to stress hormone are not well defined. This review has focused on diverse molecular paths that come out in response to chronic psychological stress via releasing of excessive glucocorticoids (GCs), involved in the aging process. GCs suppress transcription of nuclear cell adhesion molecules which impair synaptic plasticity, memory formation, and cognitive ability. Again, GCs promote muscle atrophy by means of motivating ubiquitin proteasome system and can repress muscle protein synthesis by inhibition of PI3-kinase/Akt pathway. GCs also inhibit interleukin-2 synthesis through suppressing T cell receptor signal that leads to loss of T cell activation, proliferation, and B-cell activation. Moreover, GCs increase the expression of collagenase-3, RANK ligand, and colony stimulating factor-1 that induce bone resorption. In general, stress-induced GCs can play causal role for aging and age-related disorders. PMID- 21972003 TI - Ectopic expression of guanylyl cyclase C and endogenous ligand guanylin correlates significantly with Helicobacter pylori infection in gastric carcinogenesis. AB - The molecular mechanisms leading to gastric carcinogenesis still remain unclear. Recently, several studies demonstrated that over-expression of guanylyl cyclase C (GCC) has been detected in intestinal-type gastric cancer (GC) and precursor lesions. Our objective was to explore the expression levels of GCC and endogenous ligands guanylin (GN) and uroguanylin (UGN) and the correlation between Helicobacter pylori (H. pylori) and GCC, GN, and UGN expressions in patients at different stages from normal mucosa to superficial gastritis, atrophic gastritis, intestinal metaplasia (IM), dysplasia, and finally adenocarcinoma. The expression of GCC and GN was absent in the distal normal gastric tissues and superficial gastritis in all cases, whereas they were measured in IM, dysplasia, and GC. The expression of GCC and GN was closely related to intestinal-type GC. From superficial gastritis to gastric carcinomas, the H. pylori positive rate was 19.7, 33.3, 69.6, 80.0, and 82.1%, respectively. The positive correlation was found between GCC and GN in IM, dysplasia, and GC. Also, the positive correlation was found between GCC, GN, and H. pylori infection in them. These results demonstrate that the detection of GCC and GN will be beneficial to diagnosis human gastric carcinoma and precancerous lesions. Ectopic expression of GCC and GN in human gastric mucosa and H. pylori infection may play an important role in the carcinogenesis of the intestinal-type GC. PMID- 21972004 TI - SNP rs2470152 in CYP19 is correlated to aromatase activity in Chinese polycystic ovary syndrome patients. AB - CYP19 encodes aromatase, a key enzyme essential for estrogen biosynthesis. Single nucleotide polymorphism (SNP) rs2470152 in CYP19 is associated with serum estradiol (E2) level and the E2/T (estradiol/testosterone) ratio. A case-control study including 661 individuals [364 polycystic ovary syndrome (PCOS) patients and 297 controls] was conducted to assess the association of SNP rs2470152 with PCOS. The subjects were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Hormone levels were analyzed among various genotypes. The genotypic distributions of rs2470152 did not differ in PCOS patients when compared to the controls. However, differences in the E2/T ratio were detected, exhibiting a lower ratio in the heterozygous TC genotype in PCOS patients (p=0.01036) and controls (p=0.000). Testosterone levels also differed between the three genotypes of PCOS patients (p=0.00625), with a higher level in the TC genotype. Therefore, rs2470152 in CYP19 was not a major etiological factor for PCOS; however, the heterozygous TC genotype may inhibit aromatase activity, resulting in hyperandrogenism, particularly in PCOS patients. PMID- 21972005 TI - Understanding atmospheric organic aerosols via factor analysis of aerosol mass spectrometry: a review. AB - Organic species are an important but poorly characterized constituent of airborne particulate matter. A quantitative understanding of the organic fraction of particles (organic aerosol, OA) is necessary to reduce some of the largest uncertainties that confound the assessment of the radiative forcing of climate and air quality management policies. In recent years, aerosol mass spectrometry has been increasingly relied upon for highly time-resolved characterization of OA chemistry and for elucidation of aerosol sources and lifecycle processes. Aerodyne aerosol mass spectrometers (AMS) are particularly widely used, because of their ability to quantitatively characterize the size-resolved composition of submicron particles (PM(1)). AMS report the bulk composition and temporal variations of OA in the form of ensemble mass spectra (MS) acquired over short time intervals. Because each MS represents the linear superposition of the spectra of individual components weighed by their concentrations, multivariate factor analysis of the MS matrix has proved effective at retrieving OA factors that offer a quantitative and simplified description of the thousands of individual organic species. The sum of the factors accounts for nearly 100% of the OA mass and each individual factor typically corresponds to a large group of OA constituents with similar chemical composition and temporal behavior that are characteristic of different sources and/or atmospheric processes. The application of this technique in aerosol mass spectrometry has grown rapidly in the last six years. Here we review multivariate factor analysis techniques applied to AMS and other aerosol mass spectrometers, and summarize key findings from field observations. Results that provide valuable information about aerosol sources and, in particular, secondary OA evolution on regional and global scales are highlighted. Advanced methods, for example a-priori constraints on factor mass spectra and the application of factor analysis to combined aerosol and gas phase data are discussed. Integrated analysis of worldwide OA factors is used to present a holistic regional and global description of OA. Finally, different ways in which OA factors can constrain global and regional models are discussed. PMID- 21972006 TI - Development and validation of a comprehensive two-dimensional gas chromatography mass spectrometry method for the analysis of phytosterol oxidation products in human plasma. AB - Phytosterol oxidation products (POPs) have been suggested to exert adverse biological effects similar to, although less severe than, their cholesterol counterparts. For that reason, their analysis in human plasma is highly relevant. Comprehensive two-dimensional gas chromatography (GC*GC) coupled with time-of flight mass spectrometry (TOF-MS) has been proven to be an extremely powerful separation technique for the analysis of very low levels of target compounds in complex mixtures including human plasma. Thus, a GC*GC/TOF-MS method was developed and successfully validated for the simultaneous quantification of ten POPs in human plasma. The calibration curves for each compound showed correlation coefficients (R(2)) better than 0.99. The detection limits were below 0.1 ng mL( 1). The recovery data were between 71.0% and 98.6% (RSDs <10% for all compounds validated). Good results were obtained for within- and between-day repeatability, with most values being below 10%. In addition, non-targeted sterol metabolites were also identified with the method. The concentrations of POPs found in human plasma in the current study are between 0.3 and 4.5 ng mL(-1), i.e., 10-100 times lower than the typical values found for cholesterol oxidation products. PMID- 21972008 TI - Suppression of alpha-MSH and IBMX-induced melanogenesis by cordycepin via inhibition of CREB and MITF, and activation of PI3K/Akt and ERK-dependent mechanisms. AB - Cordycepin has been a traditional medicine in China and Korea for centuries. This study explored the inhibitory effect of cordycepin on melanogenesis and the relative molecular mechanisms. Cordycepin inhibited melanin synthesis-related enzymes, such as tyrosinase, tyrosinase-related protein-1 (TRP1) and tyrosinase related protein-2 (TRP2). alpha-MSH and IBMX were reported as melanin synthesis enhancers. Both of them could increase intracellular melanin synthesis by activation of the microphthalmia-associated transcription factor (MITF) signaling pathway. In the MITF pathway, the phosphorylation of cAMP related binding protein (CREB) activated the transcription of MITF, resulting in increasing melanin synthesis. Cordycepin also decreased the phosphorylation of CREB induced by alpha MSH and IBMX in B16F10 melanoma cells. Accordingly, cordycepin inhibited melanogenesis signaling pathways by activating ERK and AKT signaling pathways to regulate the suppression of MITF and its downstream pathways including tyrosinase, TRP1 and TRP2. These results indicate the role of cordycepin as a potent depigmenting agent for cosmetics. PMID- 21972009 TI - Molecular catalysts confined on and within molecular layers formed on a si(111) surface with direct si-C bonds. AB - Two examples of confined molecular catalysts are presented. PtCl(4) (2-) complexes are attached to a thiol-terminated monolayer by ligand exchange of Cl( ) with a thiolate group and incorporated in a multilayer of viologen moieties by ion exchange. All Cl(-) ligands are replaced by OH(-) or H(2) O before HER takes place. Ex situ and in situ XAFS measurements confirm that the Pt complexes accelerate HER without being converted into Pt particles. PMID- 21972007 TI - Combined fish oil and astaxanthin supplementation modulates rat lymphocyte function. AB - PURPOSE: Higher intakes of n-3 polyunsaturated fatty acids that are abundant in marine fishes have been long described as a "good nutritional intervention" with increasing clinical benefits to cardiovascular health, inflammation, mental, and neurodegenerative diseases. The present study was designed to investigate the effect of daily fish oil (FO-10 mg EPA/kg body weight (BW) and 7 mg DHA/kg BW) intake by oral gavage associated with the antioxidant astaxanthin (ASTA-1 mg/kg BW) on the redox metabolism and the functional properties of lymphocytes from rat lymph nodes. METHODS: This study was conducted by measurements of lymphocyte proliferation capacity, ROS production [superoxide (O2(*-)) and hydrogen peroxide (H2O2)], nitric oxide (NO(*)) generation, intracellular calcium release, oxidative damage to lipids and proteins, activities of major antioxidant enzymes, GSH/GSSG content, and cytokines release. RESULTS: After 45 days of FO + ASTA supplementation, the proliferation capacity of activated T- and B-lymphocytes was significantly diminished followed by lower levels of O2(*-), H2O2 and NO(*) production, and increased activities of total/SOD, GR and GPx, and calcium release in cytosol. ASTA was able to prevent oxidative modification in cell structures through the suppression of the oxidative stress condition imposed by FO. L: -selectin was increased by FO, and IL-1beta was decreased only by ASTA supplementation. CONCLUSION: We can propose that association of ASTA with FO could be a good strategy to prevent oxidative stress induced by polyunsaturated fatty acids and also to potentiate immuno-modulatory effects of FO. PMID- 21972010 TI - A mental health needs assessment of urban American Indian youth and families. AB - American Indian (AI) youth experience significant mental health disparities. The majority of AI youth live in urban areas, yet urban AI youth are underserved and unstudied. This manuscript describes a qualitative study of community mental health needs in an urban population of AI youth, conducted as part of the planning process for a system of care (SOC). Participants included 107 urban AI youth and families that participated in one of 16 focus groups assessing mental health needs and services. Forty-one percent of participants were youth or young adults. Data were coded and analyzed using qualitative software and then further analyzed and interpreted in partnership with a community research workgroup. Results indicated various community characteristics, mental health and wellness needs, and service system needs relevant to developing a system of care in this community. Key community, cultural, and social processes also emerged, reinforcing the importance of broader system changes to promote a sustainable SOC. These systems/policy changes are reviewed in the context of previous literature proposing necessary systems change to support behavioral health care in AI communities as well as to ensure that SOC implementation is consistent with core values and philosophy across all communities. PMID- 21972011 TI - A combination of in situ ESR and in situ NMR spectroelectrochemistry for mechanistic studies of electrode reactions: the case of p-benzoquinone. AB - A combined in situ NMR and in situ ESR spectroelectrochemical study of a reaction mechanism is presented detecting and describing the whole number of paramagnetic and diamagnetic intermediates and final products in an electrode reaction. While in situ NMR spectroelectrochemistry provides a powerful method for the study of structural or electronic changes of diamagnetic molecules in any electrochemical reaction mechanism, in situ ESR spectroelectrochemistry is the method of choice to detect paramagnetic structures and to characterise their electronic state via the g-value and hyperfine splitting in redox reactions. To demonstrate the power of this combination of magnetic spectroscopies in electrochemistry, the reduction of p-benzoquinone to hydroquinone is followed by both these spectroelectrochemical methods at selected pH values, thus considering the influence of the proton on the reaction mechanism. The results of both in situ spectroelectrochemical methods at the same redox system are used to get the complete reaction mechanism of p-benzoquinone at electrodes in aqueous solutions. PMID- 21972012 TI - In vitro evaluation of glass-glass ceramic thermoseed-induced hyperthermia on human osteosarcoma cell line. AB - The use of biomaterials as implantable thermoseeds under the action of an external magnetic field is a very interesting methodology to focus the heat into the target tumors as osteosarcoma. In this study, biocompatible and bioactive G15GC85 thermoseeds, tailored through the combination of sol-gel glasses (G) with a magnetic glass ceramic (GC), were used to induce hyperthermia on cultured human osteosarcoma cells after exposition to alternating magnetic field (MF, 100 kHz/200 Oe). G15GC85 magnetic glass-glass ceramic thermoseeds induced in vitro effective hyperthermia with drastic reduction in proliferation of human osteosarcoma Saos-2 cells and high increase of apoptotic cells after two 40 min consecutive sessions of MF. Deep cell morphology alterations were observed after this hyperthermic treatment, and the proteomic analysis revealed modification of gamma actin molecular properties related to cytoskeleton alterations. These results indicate that G15GC85 thermoseeds allow to induce in vitro effective hyperthermia on human osteosarcoma cells. PMID- 21972013 TI - Structural definition of trehalose 6-monomycolates and trehalose 6,6'-dimycolates from the pathogen Rhodococcus equi by multiple-stage linear ion-trap mass spectrometry with electrospray ionization. AB - The cell wall of the pathogenic bacterium Rhodococcus equi (R. equi) contains abundant trehalose monomycolate (TMM) and trehalose dimycolate (TDM), the glycolipids bearing mycolic acids. Here, we describe multiple-stage (MS(n)) linear ion-trap (LIT) mass spectrometric approaches toward structural characterization of TMM and TDM desorbed as [M + Alk](+) (Alk = Na, Li) and as [M + X](-) (X = CH(3)CO(2), HCO(2)) ions by electrospray ionization (ESI). Upon MS(n) (n=2, 3, 4) on the [M + Alk](+) or the [M + X](-) adduct ions of TMM and TDM, abundant structurally informative fragment ions are readily available, permitting fast assignment of the length of the meromycolate chain and of the alpha-branch on the mycolyl residues. In this way, structures of TMM and TDM isolated from pathogenic R. equi strain 103 can be determined. Our results indicate that the major TMM and TDM molecules possess 6, and/or 6'-mycolyl groups that consist of mainly C14 and C16 alpha-branches with meromycolate branches ranging from C18 to C28, similar to the structures of the unbound mycolic acids found in the cell envelope. Up to 60 isobaric isomers varying in chain length of the alpha-branch and of the meromycolate backbone were observed for some of the TDM species in the mixture. This mass spectrometric approach provides a direct method that affords identification of various TMM and TDM isomers in a mixture of which the complexity of this lipid class has not been previously reported using other analytical methods. PMID- 21972014 TI - The competition of charge remote and charge directed fragmentation mechanisms in quaternary ammonium salt derivatized peptides--an isotopic exchange study. AB - Derivatization of peptides as quaternary ammonium salts (QAS) is a promising method for sensitive detection by electrospray ionization tandem mass spectrometry (Cydzik et al. J. Pept. Sci. 2011, 17, 445-453). The peptides derivatized by QAS at their N-termini undergo fragmentation according to the two competing mechanisms - charge remote (ChR) and charge directed (ChD). The absence of mobile proton in the quaternary salt ion results in ChR dissociation of a peptide bond. However, Hofmann elimination of quaternary salt creates an ion with one mobile proton leading to the ChD fragmentation. The experiments on the quaternary ammonium salts with deuterated N-alkyl groups or amide NH bonds revealed that QAS derivatized peptides dissociate according to the mixed ChR-ChD mechanism. The isotopic labeling allows differentiation of fragments formed according to ChR and ChD mechanisms. PMID- 21972015 TI - Oxidative and nitrosative stress on phagocytes' function: from effective defense to immunity evasion mechanisms. AB - Although oxygen, nitrogen, and chlorine reactive species have been associated with disease pathogenesis, their partial absence is very harmful to the body's innate immune defense. Lacking of adequate release of free radicals from activated phagocytes is related to impaired ability on fungi, bacteria, and protozoa killing. We constructed an updated conceptual landmark regarding the paramount role of free radicals in phagocyte defense systems (phagocyte oxidase, myeloperoxidase, and nitric oxide/peroxynitrite system) on natural immunity. Diverse fungal, bacterial and protozoal pathogens evade the phagocytes' oxidative/nitrosative burst though antioxidant genes, enzymes and proteins. The most important evasion mechanisms were also described and discussed. These interconnected systems were reviewed and discussed on the basis of knowledge from relevant research groups around the globe. Phagocyte-derived free radicals are essential to destroy important human pathogens during the course of innate immunity. PMID- 21972016 TI - NK cells prevalence, subsets and function in viral hepatitis C. AB - Innate immunity appears to play an important role in the pathogenesis of viral hepatitis C. Among various cell subsets of this immunity natural killer (NK) cells raised particular interest. These cells are abundant in liver, possess significant cytotoxic potential and show links with adaptive immunity. They play important role, particularly in the acute phase of viral infections, including hepatitis C. They exhibit various types of receptors, either inhibitory or activating, that are able to react with distinct ligands on infected cells. Homozygosity of some receptors, namely KIR2DL3 reacting with recipient HLA-C1 antigens is a herald of good prognosis in hepatitis C virus (HCV) infection. In the early stage of the latter, both the prevalence and the cytotoxicity of NK cells are increased. Their inhibitory receptors are down regulated whereas activating ones are up regulated. Interferon-gamma secreted by NK56(+bright) NK cells has a direct cytotoxic effect on infected hepatocytes. In contrast, in the chronic phase of HCV liver disease both, the prevalence and function of NK cells are impaired. Nevertheless, their cytotoxicity contributes to liver injury. Cells show change in the polarization profile from NK1 to NK2, manifested by secretion of immunosuppressive cytokines. Some HCV peptides are inhibitory for NK cells leading to the reduction of their antiviral activity. The unwanted effects of HCV peptides can be at least partly reversed by the antiviral therapy. PMID- 21972017 TI - The transcription factor PU.1 is a critical regulator of cellular communication in the immune system. AB - PU.1 is an E26 transformation-specific family transcription factor that is required for development of the immune system. PU.1 functions at both early and late stages of lymphoid and myeloid differentiation. At least 110 direct target genes of PU.1 have been identified since its discovery in 1988. We used the published literature to determine if aspects of PU.1 function can be inferred from the identity of target genes that are directly activated. This analysis revealed that 61% of described PU.1 target genes encode extracellular proteins or transmembrane proteins, most of which are involved in cellular communication. The genes activated by PU.1 can be grouped into pathways based on function. Specific examples of cellular communication pathways regulated by PU.1 include (1) antibodies and antibody receptors, (2) cytokines and cytokine receptors regulating leukocyte growth and development, and (3) cytokines and cytokine receptors regulating inflammation. As a consequence of mutation or repression of the gene encoding PU.1, hematopoietic progenitors may be generated but there is a "failure to thrive" because they cannot interact with their environment. The loss of cellular communication caused by reduced PU.1 levels can lead to leukemia. In summary, PU.1 is a critical regulator of cellular communication in the immune system. PMID- 21972018 TI - Beclin 1 is involved in regulation of apoptosis and autophagy during replication of ectromelia virus in permissive L929 cells. AB - Several reports have brought to light new and interesting findings on the involvement of autophagy and apoptosis in pathogenesis of viral and bacterial diseases, as well as presentation of foreign antigens. Our model studies focused on the involvement of apoptosis during replication of highly virulent Moscow strain of ectromelia virus (ECTV-MOS). Here, we show evidence that autophagy is induced during mousepox replication in a cell line. Fluorescence microscopy revealed increase of LC3 (microtubule-associated protein 1 light chain 3) aggregation in infected as opposed to non-infected control L929 cells. Furthermore, Western blot analysis showed that replication of ECTV-MOS in L929 cells led to the increase in LC3-II (marker of autophagic activity) expression. Beclin 1 strongly colocalized with extranuclear viral replication centers in infected cells, whereas expression of Bcl-2 decreased in those centers as shown by fluorescence microscopy. Loss of Beclin 1-Bcl-2 interaction may lead to autophagy in virus-infected L929 cells. To assess if Beclin 1 has a role in regulation of apoptosis during ECTV-MOS infection, we used small interfering RNA directed against beclin 1 following infection. Early and late apoptotic cells were analyzed by flow cytometry after AnnexinV and propidium iodide staining. Silencing of beclin 1 resulted in decreased percentage of early and late apoptotic cells in the late stage of ECTV-MOS infection in L929 cells. We conclude that Beclin 1 plays an important role in regulation of both, autophagy and apoptosis, during ECTV-MOS replication in L929 permissive cells. PMID- 21972020 TI - Synthetic studies on amaryllidaceae and other terrestrially derived alkaloids. AB - The total syntheses of a wide range of terrestrially derived alkaloids, especially ones isolated from members of the Amaryllidaceae family, are described. Two recurring themes associated with these syntheses are the use of two types of building blocks, namely ring-fused cyclopropanes, especially geminally-dihalogenated ones, and enzymatically derived cis-1,2-dihydrocatechols. These have often served as precursors to 2- or 3-halogenated 2-cyclohexen-1-ols that are themselves engaged in cross-coupling reactions, radical addition elimination processes and/or Claisen- or Overman-type rearrangements so as to construct the highly functionalized six-membered rings associated with the target alkaloids. PMID- 21972021 TI - Charge transport in organic semiconductors. AB - Modern optoelectronic devices, such as light-emitting diodes, field-effect transistors and organic solar cells require well controlled motion of charges for their efficient operation. The understanding of the processes that determine charge transport is therefore of paramount importance for designing materials with improved structure-property relationships. Before discussing different regimes of charge transport in organic semiconductors, we present a brief introduction into the conceptual framework in which we interpret the relevant photophysical processes. That is, we compare a molecular picture of electronic excitations against the Su-Schrieffer-Heeger semiconductor band model. After a brief description of experimental techniques needed to measure charge mobilities, we then elaborate on the parameters controlling charge transport in technologically relevant materials. Thus, we consider the influences of electronic coupling between molecular units, disorder, polaronic effects and space charge. A particular focus is given to the recent progress made in understanding charge transport on short time scales and short length scales. The mechanism for charge injection is briefly addressed towards the end of this chapter. PMID- 21972019 TI - Microarray analysis reveals age-related differences in gene expression during the development of osteoarthritis in mice. AB - OBJECTIVE: To better understand the contribution of age to the development of osteoarthritis (OA). METHODS: Surgical destabilization of the medial meniscus (DMM) was used to model OA in 12-week-old and 12-month-old male C57BL/6 mice. OA severity was evaluated histologically. RNA used for microarray and real-time polymerase chain reaction analysis was isolated from joint tissue collected from the medial side of the joint, including cartilage, meniscus, subchondral bone, and the joint capsule with synovium. Computational analysis was used to identify patterns of gene expression, and immunohistochemistry was used to evaluate tissue distribution of selected proteins. RESULTS: OA was more severe in older mice than in young mice. Only 55 genes showed a similar expression with DMM-induced OA in the 2 age groups, while 493 genes showed differential expression, the majority having increased expression in older mice. Functional categories for similarly expressed genes included extracellular matrix- and cell adhesion-related genes; differentially expressed genes included those related to muscle structure and development and immune response genes. Comparison of expression in sham-operated control joints revealed an age-related decrease in matrix gene expression and an increase in immune and defense response gene expression. Interleukin-33 was present in multiple joint tissue cells, while CCL21 was more localized to chondrocytes and meniscal cells. Periostin was found in the extracellular matrix of cartilage and meniscus. CONCLUSION: Age affects both the basal pattern of gene expression in joint tissues and the response to surgically induced OA. Examining tissue from the joint beyond only cartilage revealed novel genes and proteins that would be important to consider in OA. PMID- 21972022 TI - Fragment screening and HIV therapeutics. AB - Fragment screening has proven to be a powerful alternative to traditional methods for drug discovery. Biophysical methods, such as X-ray crystallography, NMR spectroscopy, and surface plasmon resonance, are used to screen a diverse library of small molecule compounds. Although compounds identified via this approach have relatively weak affinity, they provide a good platform for lead development and are highly efficient binders with respect to their size. Fragment screening has been utilized for a wide range of targets, including HIV-1 proteins. Here, we review the fragment screening studies targeting HIV-1 proteins using X-ray crystallography or surface plasmon resonance. These studies have successfully detected binding of novel fragments to either previously established or new sites on HIV-1 protease and reverse transcriptase. In addition, fragment screening against HIV-1 reverse transcriptase has been used as a tool to better understand the complex nature of ligand binding to a flexible target. PMID- 21972023 TI - Fluorous methods for the synthesis of peptides and oligonucleotides. AB - The non-covalent affinity of a perfluoro chain towards similar has been exploited by many to separate fluorous tagged compounds from non-fluorous compounds by F SPE or F-LLE. This purification strategy found its application across diverse fields including peptide and oligonucleotide synthesis where even slight inefficient couplings result in deletion sequences that are often difficult to remove from the target sequence. Two commonly employed strategies to address this problem involve end-tagging the target sequence or capping the deletion sequences with fluorous tags. Solution phase syntheses using soluble fluorous supports are easier and quicker. These approaches are reviewed here in detail. PMID- 21972024 TI - Thiourea based fluorous organocatalyst. AB - This review deals with general and significant development of the fluorous organocatalysts based on thiourea. The applications of fluorous technology are briefly discussed. The implementations of thiourea based catalysts in organic synthesis are focused on in the chapter. PMID- 21972025 TI - Fluorous organic hybrid solvents for non-fluorous organic synthesis. AB - The rapid progress in fluorous chemistry shed the light on the use of fluorous organic hybrid solvents for fluorous reactions; however, these hybrid solvents also have good potentials as solvents for ordinary organic synthesis. This chapter will survey the state of the art of the fluorous organic hybrid solvents as green substitutes for traditional organic solvents. PMID- 21972027 TI - Structural, physical, and chemical properties of fluorous compounds. AB - The sizes and structures of fluorous molecules are analyzed, particularly with respect to the helical conformations of perfluoroalkyl segments and their phase separation in crystal lattices. Basic molecular properties, bond energies, and special bonding motifs are reviewed. Solubility, adsorption, and related phenomena are treated. Miscibilities of fluorous solvents, and partition coefficients of solutes in fluorous/organic biphase mixtures, are analyzed. Electronic effects and NMR properties are discussed, and some reactions involving the fluorinated parts of fluorous substances are presented. PMID- 21972026 TI - Incorporation of fluorous glycosides to cell membrane and saccharide chain elongation by cellular enzymes. AB - A series of fluorous-tagged glycosides with different number of fluorine atoms are incorporated into the cells, transported to Golgi, elongated by cellular enzymes, and then released to the culture medium. Fluorine content strongly affects on the affinity for cell membrane and glycosylation. Essentially, the fluorocarbon chain in fluorous compound and the hydrocarbon chain are not miscible. However, the fluorous-tagged glycosides have affinity for cell membrane because of its amphiphilicity. The affinity of fluoro-amphiphilic compound for cell membrane is discussed using critical micelle concentration. The separation of glycosylated products by solvent extraction or fluorous solid phase extraction cartridges is also discussed. PMID- 21972028 TI - Fluorous hydroformylation. AB - The application of fluorous phosphine-modified catalysts for the hydroformylation of olefins is reviewed. PMID- 21972030 TI - In silico synergism and antagonism of an anti-tumour system intervened by coupling immunotherapy and chemotherapy: a mathematical modelling approach. AB - Based on the logistic growth law for a tumour derived from enzymatic dynamics, we address from a physical point of view the phenomena of synergism, additivity and antagonism in an avascular anti-tumour system regulated externally by dual coupling periodic interventions, and propose a theoretical model to simulate the combinational administration of chemotherapy and immunotherapy. The in silico results of our modelling approach reveal that the tumour population density of an anti-tumour system, which is subject to the combinational attack of chemotherapeutical as well as immune intervention, depends on four parameters as below: the therapy intensities D, the coupling intensity I, the coupling coherence R and the phase-shifts Phi between two combinational interventions. In relation to the intensity and nature (synergism, additivity and antagonism) of coupling as well as the phase-shift between two therapeutic interventions, the administration sequence of two periodic interventions makes a difference to the curative efficacy of an anti-tumour system. The isobologram established from our model maintains a considerable consistency with that of the well-established Loewe Additivity model (Tallarida, Pharmacology 319(1):1-7, 2006). Our study discloses the general dynamic feature of an anti-tumour system regulated by two periodic coupling interventions, and the results may serve as a supplement to previous models of drug administration in combination and provide a type of heuristic approach for preclinical pharmacokinetic investigation. PMID- 21972031 TI - Success rate of a biological invasion in terms of the spatial distribution of the founding population. AB - We analyze the role of the spatial distribution of the initial condition in reaction-diffusion models of biological invasion. Our study shows that, in the presence of an Allee effect, the precise shape of the initial (or founding) population is of critical importance for successful invasion. Results are provided for one-dimensional and two-dimensional models. In the one-dimensional case, we consider initial conditions supported by two disjoint intervals of length L/2 and separated by a distance alpha. Analytical as well as numerical results indicate that the critical size L*(alpha) of the population, where the invasion is successful if and only if L > L*(alpha), is a continuous function of alpha and tends to increase with alpha, at least when alpha is not too small. This result emphasizes the detrimental effect of fragmentation. In the two dimensional case, we consider more general, stochastically generated initial conditions u0, and we provide a new and rigorous definition of the rate of fragmentation of u0. We then conduct a statistical analysis of the probability of successful invasion depending on the size of the support of u0 and the fragmentation rate of u0. Our results show that the outcome of an invasion is almost completely determined by these two parameters. Moreover, we observe that the minimum abundance required for successful invasion tends to increase in a non linear fashion with the fragmentation rate. This effect of fragmentation is enhanced as the strength of the Allee effect is increased. PMID- 21972032 TI - Head-to-head comparison of eight late gadolinium-enhanced cardiac MR (LGE CMR) sequences at 1.5 tesla: from bench to bedside. AB - PURPOSE: To compare-theoretically and experimentally-clinically available two dimensional/three-dimensional (2D/3D), breathhold and non-breathhold, inversion recovery (IR) gradient-echo (GRE) sequences used to differentiate between nonviable injured and normal myocardium with late gadolinium-enhanced techniques (IR-GRE2D sequence is used as a reference), and to evaluate their respective clinical benefit. MATERIALS AND METHODS: Six breathhold (2D-IR-GRE, 3D-IR-GRE, balanced steady-state free precession 2D-IR-bSSFP and 3D-IR-bSSFP, phase sensitive 2D-PSIR-GRE, and 2D-PSIR-bSSFP) and two non-breathhold late gadolinium enhanced techniques (single-shot 2D-ssbSSFP and 2D-PSIR-ssbSSFP) were consecutively performed in 32 coronary artery disease patients with chronic myocardial infarction. Qualitative assessment and manual planimetry were performed by two independent observers. Quantitative assessment was based on percentage signal intensity elevation between injured and normal myocardium and contrast-to-noise ratio. Theoretical simulations were compared with experimental measurements performed on phantoms with various concentrations of gadolinium. RESULTS: The 3D-IR-GRE image quality appeared better than the other 2D and 3D sequences, showing better delineation of complex nontransmural lesions, with significantly higher percentage signal intensity and contrast-to-noise ratio. PSIR techniques appeared more limited in differentiating sub-endocardial lesions and intracavity blood pool, but in all other cases were comparable to the other techniques. Single-shot PSIR-ssbSSFP appeared to be a valuable alternative technique when breathhold cannot be achieved. CONCLUSION: We recommend 3D-IR-GRE as the method of choice for late gadolinium-enhanced cardiac magnetic resonance imaging in clinical practice. PMID- 21972033 TI - Rhodium-catalyzed annulation of N-benzoylsulfonamide with isocyanide through C-H activation. PMID- 21972034 TI - Estimation of external gamma radiation dose in the area of Bory Stobrawskie forests (PL). AB - The study assessed the radiological risks associated with the presence of natural and artificial radionuclides in the Bory Stobrawskie forests (PL). Using the conversion factors given by UNSCEAR and the measurements results of (232)Th series, (238)U series, (40)K, and (137)Cs specific activities in the 10-cm soil layer the values of absorbed dose (D) and the annual effective dose equivalent derived from terrestrial gamma radiation (E) were calculated. The calculated dose was compared with doses directly measured on the area studied. PMID- 21972035 TI - Unusual coelom formation in the direct-type developing sand dollar Peronella japonica. AB - Peronella japonica is a sand dollar with a zygote that develops into an abbreviated pluteus but then metamorphoses on day three. The adult rudiment formation is unique; it uses a median position of the hydrocoel and a stomodeum like invagination of vestibule that covers the dorsal side of the hydrocoel. However, the developmental processes underlying coelom formation remain unclear. In this study, we examined this process by reconstructing three-dimensional images from serial sections of larvae. We show that the left coelom developed by both schizocoely and enterocoely from the archenteron tip, whereas the hydrocoel and right coelom formed by enterocoely from the archenteron. This coelom formation arranged the coelomic compartments directly along the adult oral-aboral axis by skipping the initial bilateral phases. Furthermore, our data indicate P. japonica retains ancestral asymmetry along the left-right axis in the location of the adult rudiment. PMID- 21972036 TI - Patterned growth of polyaniline nanowire arrays on a flexible substrate for high performance gas sensing. AB - Uniform patterning of polyaniline nanowire arrays on a wafer-sized flexible substrate is achieved by combining photolithography and in situ polymerization techniques. Chemical gas sensors based on the patterned polyaniline nanowire arrays exhibit excellent performance because of their highly ordered morphology and large specific surface area. PMID- 21972037 TI - TR-FRET cellular assays for interrogating posttranslational modifications of histone H3. AB - Posttranslational modifications such as phosphorylation, acetylation, and methylation play important roles in regulating the structures and functions of histones, which in turn regulate gene expression and DNA repair and replication. Histone-modifying enzymes, such as deacetylases, methyltransferases and demethylases, have been pursued as therapeutic targets for various diseases. However, detection of the activities of these enzymes in high-throughput cell based formats has remained challenging. The authors have developed high throughput LanthaScreen cellular assays for Histone H3 site-specific modifications. These assays use cells expressing green fluorescence protein tagged Histone H3 transiently delivered via BacMam and terbium-labeled anti Histone H3 modification-specific antibodies. Robust time-resolved Forster resonance energy transfer signals were detected for H3 lysine-9 acetylation and dimethylation (H3K9me2), serine-10 phosphorylation, K4 di- and trimethylation, and K27 trimethylation. Consistent with previous reports, hypoxic stress increased K4 methylation levels, and methyltransferase G9a inhibitor UNC-0638 decreased K9me2 levels significantly, with little effects on other modifications. To demonstrate the utility of this assay platform in screening, the K9 acetylation assay was used to profile the Enzo Epigenetics Library. Twelve known HDAC inhibitors were identified as hits and followed up in a dose-response format. In conclusion, this assay platform enables high-throughput cell-based analysis of diverse types of posttranslational modifications of Histone H3. PMID- 21972038 TI - Fluorescence-based methods for screening writers and readers of histone methyl marks. AB - The histone methyltransferase (HMT) family of proteins consists of enzymes that methylate lysine or arginine residues on histone tails as well as other proteins. Such modifications affect chromatin structure and play a significant regulatory role in gene expression. Many HMTs have been implicated in tumorigenesis and progression of multiple malignancies and play essential roles in embryonic development and stem cell renewal. Overexpression of some HMTs has been observed and is correlated positively with various types of cancer. Here the authors report development of a continuous fluorescence-based methyltransferase assay in a 384-well format and its application in determining kinetic parameters for EHMT1, G9a, PRMT3, SETD7, and SUV39H2 as well as for screening against libraries of small molecules to identify enzyme inhibitors. They also report the development of a peptide displacement assay using fluorescence polarization in a 384-well format to assay and screen protein peptide interactions such as those of WDR5 and EED, components of MLL and EZH2 methyltransferase complexes. Using these high-throughput screening methods, the authors have identified potent inhibitors and ligands for some of these proteins. PMID- 21972039 TI - DAS28 and Rheumatoid Arthritis: The Need for Standardization. AB - Disease Activity Score in 28 Joints (DAS28) scoring in rheumatoid arthritis (RA) is now recommended as a basis for clinical decisions about treatment initiation and alteration. The British Society of Rheumatology suggests that most RA patients should have a DAS28 assessment at every clinic visit, to monitor disease activity and the impact of therapy. Establishing an accurate baseline assessment of DAS28, with regular re-evaluation, is considered crucial, so that progress towards a defined target of remission (or low disease activity) can be measured. The Treat-to-Target initiative, launched in March 2010, is now impacting on clinical practice throughout the UK and Europe. One of its key recommendations is that patients should be regularly monitored using validated composite measures of disease activity that include joint assessments. DAS28 is recommended as one of the most useful of these methods but, although it is becoming more widely adopted and training is ongoing, supported by materials produced by the European League Against Rheumatism (EULAR), the variability inherent in the four components of DAS28 means that standardization of practice methods is now an important issue. This short report details some of the pitfalls that can occur when applying DAS28 in clinical practice and suggests some workable solutions to enable departments to set up their own standard operating procedure. PMID- 21972040 TI - Germline mutations of the VHL gene in seven Chinese families with von Hippel Lindau disease. AB - Von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome caused by mutations or deletions within the VHL tumor-suppressor gene, but VHL germline mutations in the Chinese have rarely been studied. To investigate the genetic profile of VHL mutations in the Chinese population, we evaluated the clinical characteristics of seven Chinese families suffering from VHL disease and determined the particular germline mutations in their VHL genes. Direct sequencing and real-time quantitative PCR was carried out. Disease-associated genetic abnormalities were identified in all of the seven families examined. Two novel intragenic germline mutations (645 G insertion and 417 G deletion) were identified and are reported for the first time. Partial VHL gene deletions in exon 1 were found in two of the seven families. Three clinically asymptomatic mutation carriers were also identified. The spectrum of VHL gene abnormalities in our group is distinct from that observed in North America, Europe and Japan. These mutations are also different from those previously identified in other Chinese VHL patients. Future meta-analysis will provide greater perspective on the Chinese VHL genetic profile. VHL gene screening can play a key role in identifying asymptomatic patients who are carriers of VHL-predisposing genetic abnormalities. PMID- 21972041 TI - [Working group head and neck presents]. PMID- 21972042 TI - [A systematic guide for reading and interpreting diagnostic accuracy studies]. PMID- 21972044 TI - Nano-photocatalytic materials: possibilities and challenges. AB - Semiconductor photocatalysis has received much attention as a potential solution to the worldwide energy shortage and for counteracting environmental degradation. This article reviews state-of-the-art research activities in the field, focusing on the scientific and technological possibilities offered by photocatalytic materials. We begin with a survey of efforts to explore suitable materials and to optimize their energy band configurations for specific applications. We then examine the design and fabrication of advanced photocatalytic materials in the framework of nanotechnology. Many of the most recent advances in photocatalysis have been realized by selective control of the morphology of nanomaterials or by utilizing the collective properties of nano-assembly systems. Finally, we discuss the current theoretical understanding of key aspects of photocatalytic materials. This review also highlights crucial issues that should be addressed in future research activities. PMID- 21972043 TI - Fast 3D Near-infrared breast imaging using indocyanine green for detection and characterization of breast lesions. AB - PURPOSE: To evaluate fast 3D near-infrared breast imaging using the optical contrast agent indocyanine green (ICG) for the detection and characterization of breast lesions. MATERIALS AND METHODS: 30 patients with suspicious breast lesions on mammography and/or ultrasound underwent fast 2 Hz 3D optical mammography before, during, and after administration of a 25 mg ICG bolus prior to needle biopsy. The bolus kinetics is analyzed using two perfusion parameters and a derived parameter: "peak amplitude" (PA), "time-to-peak" (TTP) and "peak-time grouped amplitude" (PTA). A receiver operating characteristic curve (ROC) analysis was performed to define a PTA cut-off for reader-independent differentiation of benign and malignant lesions. 8 patients had to be excluded from data analysis. Overall 14 breasts bearing a malignant lesion, 8 breasts bearing a benign lesion and 3 healthy breasts were analyzed. RESULTS: The cut-off based PTA analysis allowed correct detection for 12 of 14 malignant lesions (tumor size: 8 - 80 mm; sensitivity = 85.7 %). Two malignant lesions were missed. In the benign study group only one fibroadenoma was detected (specificity = 87.5 %). The PTA values differed significantly between the benign group and the malignant group (Mann-Whitney U-test, p < 0.05). Breasts with malignant lesions showed higher peaks at early time-points in ICG perfusion. CONCLUSION: Early perfusion analysis of ICG-enhanced 3D fast optical mammography revealed different enhancement patterns for benign and malignant lesions. This approach might help with the detection of malignant breast lesions and the differentiation from benign lesions. PMID- 21972045 TI - Impact of bladder-derived acellular matrix, growth factors, and extracellular matrix constituents on the survival and multipotency of marrow-derived mesenchymal stem cells. AB - We investigate the effect of bladder-derived acellular matrix (ACM) on bone marrow mesenchymal stem cells (BM-MSC) growth, survival, and differentiation, and evaluate the effect of collagen I and IV on BM-MSC differentiation potential to SMC. BM-MSCs isolated from CD1(_) mice were characterized by surface markers and differentiation into different lineages. BM-MSC SMC potential was further evaluated in stem cell medium alone or supplemented with TGF-beta1 and recombinant human platelet-derived growth factor (PDGF-BB) on plastic, collagen I and IV using western blot. Furthermore, BM-MSCs were seeded on porcine derived ACM-fortified with hyaluronic acid and cultured in Mesencult+-growth factors, bone, or fat induction media for 3 weeks. Seeded constructs were evaluated by H&E, Ki67 assay, Oil red O, and Alizarin red stain. SMC differentiation was semiquantified via immunohistochemistry. BM-MSCs differentiated into fat and bone when induced. In Mesencult, BM-MSCs differentiated into SMC, expressing alpha SMA, calponin, and MHC. BM-MSCs cultured on collagen I and IV reduced expression of SMC and MHC compared to plastic. On ACM-HA, BM-MSCs maintained multipotent state by differentiating to bone and fat when induced. In Mesencult, BM-MSC seeded ACM-HA expressed alpha-SMA, calponin, and MHC. TGF-beta1 and PDGF-BB enhanced SMC differentiation on collagens and ACM-HA. SMC proteins expression by BM-MSC varies depending on culture substrate. SMC markers are expressed higher on plastic and lower on collagen I, IV, and ACM-HA, suggesting these substrates preferentially maintain undifferentiated state of BM-MSC, which could be advantageous for incorporation of cell-seeded grafts to permit host modulation of tissue regeneration. PMID- 21972047 TI - Unconscious priming of task sets: the role of spatial attention. AB - Unconscious stimuli activate task sets, mental programs that orchestrate performance of complex tasks, but the role of attention in such effects has not been addressed. In previous studies, unconscious prime stimuli appeared at attended locations and were explicitly specified in the task instructions; spatial attention to the prime and/or a specific conscious attentional set may thus be required for such unconscious activation to arise. In the present experiments, a learning phase established associations between unconscious prime stimuli and performance of two tasks. These associations influenced task performance in a subsequent test phase, even though the primes were not specified in current task instructions. This is the first demonstration that unconscious stimuli can prime task sets independently of a current attentional set that specifies stimulus-task mappings. Such priming was not influenced by spatial attention cues, in contrast to clear attention influences in comparison trials that mimicked conditions employed by previous studies. PMID- 21972046 TI - Orienting attention to locations in mental representations. AB - Many cognitive processes depend on our ability to hold information in mind, often well beyond the offset of the original sensory input. The capacity of this visual short-term memory (VSTM) is limited to around three to four items. Recent research has demonstrated that the content of VSTM can be modulated by top-down attentional biases. This has been demonstrated using retrodictive spatial cues, termed "retro-cues," which orient subjects' attention to spatial locations within VSTM. In the present article, we tested whether the use of these cues is modulated by memory load and cue delay. There are a number of important conclusions: (1) Top-down biases can operate on very brief iconic traces as well as on older VSTM representations (Exp. 1). (2) When operating within capacity, subjects use the cue to prioritise where they initiate their memory search, rather than to discard uncued items (Exps. 2 and 3). (3) When capacity is exceeded, there is little benefit to top-down biasing relative to a neutral condition; however, unattended items are lost, with there being a substantial cost of invalid spatial cueing (Exp. 3). (4) These costs and benefits of orienting spatial attention differ across iconic memory and VSTM representations when VSTM capacity is exceeded (Exp. 4). PMID- 21972048 TI - Magnitude of force perception errors during static contractions of the knee extensors in healthy young and elderly individuals. AB - The accuracy of force perception during muscular contraction has not been studied extensively, despite its importance in rehabilitation and training. The purpose of this study was to quantify the errors made by healthy young and elderly individuals in their perceptions of force produced at the knee. Four different tasks were used to evaluate the perception of force and the effect of a sensory motor reference and simultaneous contraction on the accuracy of perception. The absolute errors were similar between groups, with values of 11.9% to 16.3%, depending on the task. The raw perception errors were greater for high levels of force (>50% of the maximal voluntary contraction, or MVC), indicating an overestimation of the forces produced for both groups. At 70% MVC, the sensory motor reference reduced raw perception errors, and the simultaneous contraction improved the accuracy of force production. Healthy young and elderly individuals had about the same capacity to judge the muscular force of their knee extensors. Therapists involved in the training of active elderly individuals should be aware that the accuracy of force perception is not perfect and that these clients have the same ability as young individuals to perceive their knee extension strength. PMID- 21972049 TI - Three-year results from a preclinical implantation study of a long-term resorbable surgical mesh with time-dependent mechanical characteristics. AB - PURPOSE: The purpose of this study was to evaluate the biocompatibility, local tissue effects and performance of a synthetic long-term resorbable test mesh (TIGR((r)) Matrix Surgical Mesh) compared to a non-resorbable polypropylene control mesh following implantation in a sheep model. METHODS: Full-thickness abdominal wall defects were created in 14 sheep and subsequently repaired using test or control meshes. Sacrifices were made at 4, 9, 15, 24 and 36 months and results in terms of macroscopic observations, histology and collagen analysis are described for 4, 9, 15, 24 and 36 months. RESULTS: The overall biocompatibility was good, and equivalent in the test and control meshes while the resorbable mesh was characterized by a collagen deposition more similar to native connective tissue and an increased thickness of the integrating tissue. The control polypropylene mesh provoked a typical chronic inflammation persistent over the 36 month study period. As the resorbable test mesh gradually degraded it was replaced by a newly formed collagen matrix with an increasing ratio of collagen type I/III, indicating a continuous remodeling of the collagen towards a strong connective tissue. After 36 months, the test mesh was fully resorbed and only microscopic implant residues could be found in the tissue. CONCLUSIONS: This study suggests that the concept of a long-term resorbable mesh with time dependent mechanical characteristics offers new possibilities for soft tissue repair and reinforcement. PMID- 21972050 TI - Absence of glutamine supplementation prevents differentiation of murine calvarial osteoblasts to a mineralizing phenotype. AB - Osteoblasts in vitro differentiate from a proliferating to a mineralizing phenotype upon transfer to a medium rich in beta-glycerophosphate and ascorbic acid. The nutritional requirements of the cells at different stages of this differentiation process are not known. In other cell types, nutritional supplementation during surgery can improve the outcome in terms of speed of patient recovery and prognosis. There is therefore the potential for supplementation at the site of fracture repair or bone grafting with critical osteoblast nutritional factors to potentially accelerate healing. In this study we investigate which common cell nutrients are required for the proliferating and mineralizing stages of osteoblast differentiation. Medium containing 5.5 mM glucose was sufficient to achieve maximal proliferation of primary calvarial osteoblasts and human osteoblast cell lines, with some added benefit of additional glutamine supplementation. However, when cells were stimulated to mineralize, glucose was insufficient to support their energetic requirements. Only when cells were supplemented with glucose together with glutamine were high levels of osteocalcin expression observed together with mineralized nodules in culture, suggesting that this would be a useful combination to assess in cultures of primary human osteoblasts to determine whether it may have beneficial effects during fracture surgery, bone grafting, and fixation of uncemented arthroplasty implants. PMID- 21972051 TI - Cause of infection in proximal tibial endoprosthetic reconstructions. AB - INTRODUCTION: The underlying cause of proximal tibial prosthetic failure by infection is unclear. We asked: (1) Is resection amount related to prosthetic infection? (2) What other risk factors are related with infection? (3) What are the survivorship and functional outcomes of proximal tibial endoprosthetic reconstruction? METHODS: Sixty-two patients who underwent modular proximal tibial megaprosthesis reconstruction were analyzed. Follow-up duration averaged 98 months (range 26-240 months). Associations between prognostic variables and prosthesis survival were assessed. RESULTS: The 10-year prosthetic survival of the 62 implants was 73.9 +/- 11.7%. Prostheses were removed in 16 (25.8%) patients for infection and 3 of the 16 underwent amputation. Resection of >37% (P = 0.016) of the tibia was found to be related to infection. Application of chemotherapy (P = 0.912) and use of synthetic material to fix the patella tendon (P = 0.2) were not found to influence prosthetic survival. Functional outcomes (determined by the MSTS system) of the 52 patients that maintained a mobile joint averaged 24.2 (81%) (range 18-28). CONCLUSIONS: Our study suggests that the amount of bone resection is related with prosthetic failure by infection, however, the contribution of other risk factors should not be underestimated. PMID- 21972052 TI - Addition of iron to erythropoiesis-stimulating agents in cancer patients: a meta analysis of randomized trials. AB - BACKGROUND: Iron supplementation could improve the hematopoietic response of erythropoiesis-stimulating agents (ESAs) used for chemotherapy-induced anemia. METHODS: We performed a meta-analysis of randomized, controlled trials by comparing parenteral or oral iron and no iron, when added to ESAs in anemic cancer patients, in order to calculate the relative risk (RR) of hematopoietic response and transfusions, the time required to reach this response, and toxicity. RESULTS: A total of 1,606 patients out of eight trials were available for meta-analysis. The RR of obtaining an hematopoietic response was 1.29 (P = 0.0001) with parenteral iron and 1.04 for oral iron (P = 0.59). The risk of transfusion was reduced with parenteral iron versus no iron (RR 0.77; P = 0.02) but not with oral iron (RR 0.68; P = 0.08). The time to reach hematopoietic response was 1 month shorter and no increased toxicity appeared with iron supplementation. CONCLUSION: Overall parenteral iron reduces the risk of transfusions by 23% and increases the chance of hematopoietic response by 29% when compared with ESAs alone. On the contrary, oral iron does not increase hematopoietic response nor transfusion rate. The significance of these results is that the proportion of non-responders to ESAs will have strongly improved and quality of life and cost ameliorated. PMID- 21972053 TI - Fundamentals of tracer kinetics for dynamic contrast-enhanced MRI. AB - Tracer kinetic methods employed for quantitative analysis of dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) share common roots with earlier tracer studies involving arterial-venous sampling and other dynamic imaging modalities. This article reviews the essential foundation concepts and principles in tracer kinetics that are relevant to DCE MRI, including the notions of impulse response and convolution, which are central to the analysis of DCE MRI data. We further examine the formulation and solutions of various compartmental models frequently used in the literature. Topics of recent interest in the processing of DCE MRI data, such as the account of water exchange and the use of reference tissue methods to obviate the measurement of an arterial input, are also discussed. Although the primary focus of this review is on the tracer models and methods for T(1) -weighted DCE MRI, some of these concepts and methods are also applicable for analysis of dynamic susceptibility contrast-enhanced MRI data. PMID- 21972054 TI - Is it worth looking? Abdominal imaging after pancreatic cancer resection: a national study. AB - INTRODUCTION: Abdominal imaging is often performed after pancreatic cancer resection. We attempted to quantify the volume and estimate the cost of complex imaging after pancreatectomy nationwide, and to determine whether their frequent use confers benefit. METHODS: Patients with pancreatic adenocarcinoma who underwent resection were identified in Surveillance, Epidemiology and End Results Medicare (1991-2005). Claims for abdominal imaging <=5 years after resection were analyzed. Patients receiving annual CT scans were identified. Univariate and multivariate analyses were performed. To assess frequency of annual CT scanning in patients with superior survival, the top decile was further analyzed. RESULTS: Eleven thousand eight hundred fifty studies were performed on 2,217 patients. Ten thousand five hundred forty-two (89%) were CT scans. The median number of scans doubled from three in 1991 to six in 2005 (p < 0.0001). Among patients with sufficient survival to allow for analysis, 51.3% received annual CT scans, while only 32.4% of top-performing patients received annual scans. Univariate analysis of the 10% of patients with superior survival did not reveal any significant benefit associated with annual imaging. CONCLUSION: Utilization of complex imaging after pancreatic cancer resection has increased substantially among Medicare beneficiaries, driven primarily by an increasing number of CT scans. Our study demonstrated no significant survival benefit among patients who received scans on a routine basis. PMID- 21972055 TI - Validation of the updated 7th edition AJCC TNM staging criteria for gastric adenocarcinoma. AB - INTRODUCTION: The recently published 7th edition of the American Joint Committee on Cancer (AJCC) TNM staging criteria for gastric adenocarcinoma contains important revisions to T and N classifications, as well as overall stage grouping. Our goal was to validate the new staging system using a cancer registry. METHODS: Retrospective review of gastric cancer patients from Surveillance, Epidemiology, and End Results (SEER) registry data (2004-2007). Patients were staged according to both 6th and 7th edition criteria, and 3-year disease-specific survival was compared. RESULTS: Thirteen thousand five hundred forty-seven patients with gastric adenocarcinoma were identified with complete staging information. When using 7th edition criteria, there was an increase in the number of patients classified as stage III (23% vs. 13%), and a decrease in patients classified as stage IV (47% vs. 53%). Statistically significant differences in 3-year disease-specific survival were observed for all T and N categories and re-staging the same population according to the 7th edition criteria improved survival discrimination. Multivariate analysis revealed statistically significant differences in survival and linear progression of hazard ratios for each stage grouping. CONCLUSIONS: The 7th edition AJCC staging criteria for gastric adenocarcinoma demonstrate better survival discrimination and risk stratification than previous criteria. PMID- 21972056 TI - Long-term outcome of percutaneous ablation in very early-stage hepatocellular carcinoma. AB - PURPOSE: The aim of this study was to investigate the long-term outcomes of percutaneous ablation (PA) of very early-stage hepatocellulcar carcinoma (HCC) with a multimodal strategy. METHODS: Written informed consent was obtained from all patients before treatment. Percutaneous ethanol injection (PEI) was performed for tumors in unfavorable locations; microwave ablation (MWA) was performed for tumors in favorable positions without a capsule; and radiofrequency ablation (RFA) was carried out in favorable tumors with a capsule. Since 2003, these advanced PA techniques have been used. RESULTS: Eighty-three patients with very early HCC were treated with PA, including 33 with PEI, 19 with MWA, and 31 with RFA. Initial complete response (CR) was achieved in 79 patients (95%). The mean follow-up period was 45 +/- 27 months (range, 24-155 months). Late treatment failure was observed in eight patients (10%), which was significantly associated with tumor size (P = 0.046) and technique advancements (P = 0.009). Sustained CR was achieved in 51 patients (61%) at the end of follow-up. Major complications occurred in two patients (2%). The 1-, 3-, 5-, and 6-year disease-free survival rates were 87%, 69%, 62%, and 59%, respectively. The 1-, 3-, 5-, and 7-year overall survival rates were 94%, 88%, 78%, and 74%, respectively. CONCLUSIONS: Treatment of very early-stage HCC using a multimodal strategy tailored to tumor characteristics achieves equivalent initial CR rates and long-term survival rates compared to surgical resection. PMID- 21972057 TI - The fruits of Cudrania tricuspidata suppress development of atopic dermatitis in NC/Nga mice. AB - The fruits of Cudrania tricuspidata are a medicinal herb in Korea, known for its antiatherosclerotic and antiinflammatory effects. Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by the influx of lymphocytes into the dermis. Using an animal model of AD, we assessed whether C. tricuspidata suppresses the development of AD-like skin lesions. Cudrania tricuspidata was administered orally to NC/Nga mice with Dermatophagoides-farinae-induced AD-like lesions for 49 days. The effects of C. tricuspidata were assessed by measuring clinical symptoms, swelling of the skin on the back and ears, and plasma concentrations of mTARC (mouse thymus and activation regulated chemokine), histamine and immunoglobulin E (IgE). We found that C. tricuspidata (60 mg/kg/day) inhibited the development of AD-like skin lesions, reduced skin dermatitis scores and inhibited the histological changes induced by repeated application of D. farinae. In addition, C. tricuspidata inhibited the increases in plasma concentrations of mTARC, histamine and IgE induced by D. farinae. These findings indicate that C. tricuspidata inhibits the development of AD-like skin lesions induced by repeated applications of D. farinae in sensitized NC/Nga by suppressing plasma concentrations of mTARC, histamine and IgE. PMID- 21972058 TI - Research on Roma health and access to healthcare: state of the art and future challenges. PMID- 21972059 TI - Clinical images: Corneal melt in a woman with longstanding rheumatoid arthritis. PMID- 21972060 TI - Job satisfaction and burnout among VA and community mental health workers. AB - Building on two independent studies, we compared burnout and job satisfaction of 66 VA staff and 86 community mental health center staff in the same city. VA staff reported significantly greater job satisfaction and accomplishment, less emotional exhaustion and lower likelihood of leaving their job. Sources of work satisfaction were similar (primarily working with clients, helping/witnessing change). VA staff reported fewer challenges with job-related aspects (e.g. flexibility, pay) but more challenges with administration. Community mental health administrators and policymakers may need to address job-related concerns (e.g. pay) whereas VA administrators may focus on reducing, and helping workers navigate, administrative policies. PMID- 21972061 TI - Effects of tobacco-related media campaigns on smoking among 20-30-year-old adults: longitudinal data from the USA. AB - OBJECTIVE: Young adults in the USA have one of the highest smoking prevalence rates of any age group, and young adulthood is a critical time period of targeting by the tobacco industry. The authors examined relationships between potential exposure to tobacco-related media campaigns from a variety of sponsors and 2-year smoking change measures among a longitudinal sample of US adults aged 20-30 years from 2001 to 2008. METHODS: Self-report data were collected from a longitudinal sample of 12,931 US young adults from age 20 to 30. These data were merged with tobacco-related advertising exposure data from Nielsen Media Research. Two-year measures of change in smoking were regressed on advertising exposures. RESULTS: Two-year smoking uptake was unrelated to advertising exposure. The odds of quitting among all smokers and reduction among daily smokers in the 2 years between the prior and current survey were positively related to anti-tobacco advertising, especially potential exposure levels of 104 155 ads over the past 24 months. Tobacco company advertising (including corporate image and anti-smoking) and pharmaceutical industry advertising were unrelated to quitting or reduction. CONCLUSION: Continued support for sustained, public health based well-funded anti-tobacco media campaigns may help reduce tobacco use among young adults. PMID- 21972062 TI - Hidden female smokers in Asia: a comparison of self-reported with cotinine verified smoking prevalence rates in representative national data from an Asian population. AB - BACKGROUND: The low smoking prevalence in Asian women may be due to under reporting. We therefore investigated gender difference in self-reported and cotinine-verified smoking prevalence rates in Korea METHODS: We analysed data from 5455 individuals (2387 men and 3068 women) in the 2008 Korean National Health and Nutrition Examination Survey. A urinary cotinine concentration of 50 ng/ml was the cut-off distinguishing smokers from non-smokers. Sensitivity analysis was done using different cut-offs of 25, 75 and 100 ng/ml. RESULTS: Cotinine-verified smoking rates were 50.0% for men and 13.9% for women, or 5.3% point and 8.0% point higher in absolute terms, respectively, than the self reported rates for men and women. Ratios of cotinine-verified to self-reported smoking rates were 2.36 for women and 1.12 for men. Of the 1620 cotinine-verified smokers, 12.1% of men and 58.9% of women classified themselves as non-smokers. Women who live with a spouse or parents tend to under-report their smoking more than those who live alone or with others. CONCLUSION: Since the number of self reported female smokers was less than half of cotinine-verified smokers, current anti-smoking policies based on self-reported smoking prevalence rates in Korea should be further directed towards hidden female smokers. Also, biochemical verification needs to be considered with national tobacco surveys in Asian countries. PMID- 21972063 TI - Is snus the same as dip? Smokers' perceptions of new smokeless tobacco advertising. AB - BACKGROUND: Since 2006, leading US cigarette companies have been promoting new snus products as line extensions of popular cigarette brands. These promotional efforts include direct mail marketing to consumers on cigarette company mailing lists. This study examines smokers' reactions to this advertising and perceptions of the new snus products. METHODS: Eight focus groups (n=65 participants) were conducted in San Francisco and Los Angeles in 2010 with smokers who received tobacco direct mail advertising. The focus group discussions assessed smokers' perceptions of the new snus products. Focus group videos were transcribed and coded using Transana software to identify common themes. RESULTS: Most participants were aware of snus advertising and many had tried free samples. Most were aware that snus was supposed to be 'different' from traditional chewing tobacco but consistently did not know why. Participants willing to try snus still identified strongly as smokers, and for some participants, trying snus reinforced their preference for smoking. Snus' major benefits were use in smoke-free environments and avoiding social stigma related to secondhand smoke. Participants were sceptical of the idea that snus was safer than cigarettes and did not see it as an acceptable substitute for cigarettes or as a cessation aid. CONCLUSIONS: Smokers repeated some messages featured in early snus advertising. Snus was not seen as an acceptable substitute for smoking or way to quit cigarettes. Current smoker responses to snus advertising are not consistent with harm reduction. PMID- 21972064 TI - Cell-cell adhesion defects in Mrj mutant trophoblast cells are associated with failure to pattern the chorion during early placental development. AB - Early placental development in mice involves patterning of the chorion into distinct layers, though little is understood regarding the interactions that regulate its organization. Here we demonstrate that keratin aggregates found in Mrj(-/-) chorionic trophoblast cells are associated with abnormal cell morphology, collapse of the actin cytoskeleton, E-cadherin and beta-catenin misexpression and extracellular matrix (ECM) disorganization. Accordingly, Mrj(-/ ) trophoblast cells in vitro are nonadherent and display erratic migratory behavior. These cells also fail to differentiate into syncytiotrophoblast cells since Rhox4b expression, a marker of syncytiotrophoblast progenitors, was maintained and Gcm1, Synb, and Syna expression failed to increase. This differentiation defect was not solely attributable to E-cadherin misexpression or ECM disorganization. However, plating Mrj-deficient cells on exogenous laminin 511 normalized their cell behavior. Lastly, we show that Mrj(-/-) chorions at embryonic day 8.5 have expanded Rhox4b expression domains and do not form normal layers of gene expression suggesting that chorion patterning requires Mrj. PMID- 21972065 TI - Transportation of silver catfish, Rhamdia quelen, in water with eugenol and the essential oil of Lippia alba. AB - This study investigated the effectiveness of eugenol and of the essential oil (EO) of Lippia alba when used in the transport of the silver catfish (Rhamdia quelen). These investigations involved measurements of blood (pH, PvO(2), PvCO(2) and HCO(3) (-)) and water parameters, survival and ionoregulatory balance. Fish (301.24 +/- 21.40 g, 28.90 +/- 1.30 cm) were transported at a loading density of 169.2 g L(-1) for 4 h in fifteen plastic bags (7 L) divided into five treatments: control, 1.5 or 3.0 MUL L(-1) of eugenol and 10 or 20 MUL L(-1) of EO of L. alba. The water parameters were measured before (0 h) and after (4 h) transportation. The net Na(+), Cl(-) and K(+) losses were higher in fish from the control treatment compared to the other treatments. The PvO(2), PvCO(2) and HCO(3) (-) increased significantly in all of the treatments at the end of the transport period. In conclusion, based on the water (total ammonia nitrogen) and ionoregulatory indicators determined in the present study, our findings indicate that eugenol and the EO of L. alba are recommended for use in the transport of this species because these anesthetics apparently reduce stress. PMID- 21972066 TI - Insights into primary ovarian insufficiency through genetically engineered mouse models. AB - Primary ovarian insufficiency (POI), also known as premature ovarian failure, is a form of hypergonadotropic hypogonadism that causes infertility in ~1% of women <40 years of age. POI has important health consequences for affected patients; however, the mechanisms that cause ovarian dysfunction are poorly understood. Elucidating these mechanisms is paramount to developing better testing and treatment strategies for affected girls and women. For obvious reasons, studies looking directly at the human ovary are extremely limited. Recently, numerous genetically engineered mouse models have been developed to investigate the molecular mechanisms that may be involved in the pathogenesis of POI. Two potential mechanisms may be involved in the development of POI: (1) abnormalities in primordial follicle activation and (2) increased rates of apoptosis of oocytes. Each of these mechanisms may lead to early depletion of ovarian follicular reserve, and thus be a contributing factor in POI. This review addresses current knowledge of molecular mechanisms controlling primordial follicle activation and oocyte apoptosis, as evidenced from various genetic mouse models. Translation of these data into clinically effective treatments or even prevention strategies may improve fertility and quality of life for women with this form of reproductive dysfunction. PMID- 21972067 TI - Probing the electromagnetic field distribution within a metallic nanodisk. AB - A Co nanolayer is used as a local probe to evaluate the vertical inhomogeneous distribution of the electromagnetic (EM) field within a resonant metallic nanodisk. Taking advantage of the direct relation between the magneto-optical activity and the electromagnetic field intensity in the Co layer, it is shown that the nonuniform EM distribution within the nanodisk under plasmon resonant conditions has maximum values close to the upper and lower flat faces, and a minimum value in the middle. PMID- 21972068 TI - Fracture risk in glucocorticoid-induced osteoporosis: comment on the article by Grossman et al. PMID- 21972070 TI - Redox-active Fe(CN)(6)(4-)-doped conducting polymers with greatly enhanced capacity as cathode materials for Li-ion batteries. PMID- 21972069 TI - Na+,K+-ATPase activity in the posterior gills of the blue crab, Callinectes ornatus (Decapoda, Brachyura): modulation of ATP hydrolysis by the biogenic amines spermidine and spermine. AB - We investigated the effect of the exogenous polyamines spermine, spermidine and putrescine on modulation by ATP, K+, Na+, NH4+ and Mg2+ and on inhibition by ouabain of posterior gill microsomal Na+,K+-ATPase activity in the blue crab, Callinectes ornatus, acclimated to a dilute medium (210/00 salinity). This is the first kinetic demonstration of competition between spermine and spermidine for the cation sites of a crustacean Na+,K+-ATPase. Polyamine inhibition is enhanced at low cation concentrations: spermidine almost completely inhibited total ATPase activity, while spermine inhibition attained 58%; putrescine had a negligible effect on Na+,K+-ATPase activity. Spermine and spermidine affected both V and K for ATP hydrolysis but did not affect ouabain-insensitive ATPase activity. ATP hydrolysis in the absence of spermine and spermidine obeyed Michaelis-Menten behavior, in contrast to the cooperative kinetics seen for both polyamines. Modulation of V and K by K+, Na+, NH4+ and Mg2+ varied considerably in the presence of spermine and spermidine. These findings suggest that polyamine inhibition of Na+,K+-ATPase activity may be of physiological relevance to crustaceans that occupy habitats of variable salinity. PMID- 21972071 TI - Infection patterns of Nile tilapia (Oreochromis niloticus L.) by two helminth species with contrasting life styles. AB - The larval stages of Bolbophorus sp. (digenean) and Amirthalingamia macracantha (cestode) are frequently reported in Oreochromis niloticus in Uganda. Little, however, is known about their infection patterns. This study examined the influence of habitat type, host size, and sex and weather patterns on the parasite populations in Uganda. A total of 650 fish were collected between January and November 2008 from a reservoir, cages, fishponds and a stream. The prevalence and intensity of A. macracantha and the prevalence of Bolbophorus sp. differed across the water bodies reflecting the effect of habitat characteristics on parasite transmission. Host sex did not significantly influence the infection patterns, although female fish were slightly more parasitized than male and sexually undifferentiated individuals. The fish size was positively correlated with helminth infections demonstrating accumulation and prolonged exposure of larger (older) fish to the parasites. The metacercariae population did not vary significantly across months, while monthly A. macracantha infection fluctuated markedly. With regard to rain seasons, higher prevalence and intensity of A. macracantha were recorded in wet season. For Bolbophorus sp., only the prevalence varied with seasons, with higher prevalence recorded in the dry season than in wet season. Generally, Bolbophorus sp. responded weakly to changes in water body, host sex and size and weather patterns. Rainfall appears to be an essential cue for coracidia hatching. PMID- 21972072 TI - Large-scale survey of the prevalence of Eimeria infections in domestic rabbits in China. AB - The current study examined the prevalence of Eimeria infections in domestic rabbits in China. A total of 480 faecal samples were collected from 48 farms in 14 provinces of China. Each faecal sample was subjected to oocyst counting and oocyst isolation. The Eimeria species from samples containing isolated and sporulated oocysts were morphologically identified under microscope. The overall prevalence of infections was 41.9% (201/480). Northwest China had the highest prevalence (70%), followed closely by Northeast China (65%) and Southwest China (62.5%). The prevalences in North China (34%) and South China (25.8%) were significantly lower. The large and medium farms had lower prevalences (34.2% and 37.2%, respectively) than the small farms (61.4%). Coccidian oocysts were found in 42.2% (76/180) of faecal samples from meat rabbits, 40% (28/70) from angora rabbits and 44.7% (85/190) from Rex rabbit. In total, ten species of Eimeria were identified from oocyst-positive samples. Concurrent infection with two to eight Eimeria species was found. E. perforans was the most prevalent species (35.2%), followed in order by E. media, E. magna, E. irresidua and E. intestinalis with prevalences of 31.3%, 28.8%, 19.4%, and 14.8%, respectively. Taken together, These results reveal the characteristics of the prevelance of rabbit coccidia infection in China, including the distribution, the scale of farming and the species, which are indispensable to the control of rabbits coccidiosis in China. PMID- 21972073 TI - An improved method for whole protein extraction from yeast Saccharomyces cerevisiae. AB - A new method for protein extraction from yeast Saccharomyces cerevisiae cells is described. This method involves the use of LiAc and NaOH to enhance the permeability of yeast cell wall prior to protein extraction with SDS-PAGE sample buffer. It was safe and efficient compared to other methods reported so far in the literature. The proteins extracted with this new method retained their immunoreactive properties and are suitable for most applications in molecular biology studies. PMID- 21972075 TI - Fanconi- Bickel Syndrome: mutation in an Indian patient. AB - Fanconi -Bickel Syndrome (FBS) is described as an autosomal recessive Glycogen Storage Disorder type XI. The underlying enzyme defect is unknown. The gene GLUT2 maps to 3q26.1-q26.3; encodes a facultative glucose transporter gene. A 6-y-old girl presented with the characteristic facial gestalt, glucose and galactose intolerance, proximal renal tubular dysfunction, hepatomegaly, and altered liver function. To confirm the diagnosis, mutation analysis was performed. Patient showed homozygous mutation in exon 9 of GLUT2 gene 1093 C>T, the mutation causing transition from arginine to stop codon at position 365 and causing premature termination of protein. The mutation was found to be causative as previously described. To the best of authors' knowledge this is first Indian patient ever reported with a mutation. Genetic testing can be employed as a method of confirming diagnosis, especially where definitive mutation can be useful for prenatal diagnosis and prognostication. PMID- 21972074 TI - Functionalization of reactive polymer multilayers with RGD and an antifouling motif: RGD density provides control over human corneal epithelial cell-substrate interactions. AB - Our study demonstrates that substrates fabricated using a "reactive" layer-by layer approach promote well-defined cell-substrate interactions of human corneal epithelial cells. Specifically, crosslinked and amine-reactive polymer multilayers were produced by alternating "reactive" deposition of an azlactone functionalized polymer [poly(2-vinyl-4,4-dimethylazlactone)] (PVDMA) and a primary amine-containing polymer [branched poly(ethylene imine)] (PEI). Advantages of our system include a 5- to 30-fold decrease in deposition time compared to traditional polyelectrolyte films and direct modification of the films with peptides. Our films react with mixtures of an adhesion-promoting peptide containing Arg-Gly-Asp (RGD) and the small molecule D-glucamine, a chemical motif which is nonfouling. Resulting surfaces prevent protein adsorption and promote cell attachment through specific peptide interactions. The specificity of cell attachment via immobilized RGD sequences was verified using both a scrambled RDG peptide control as well as soluble-RGD competitive assays. Films were functionalized with monotonically increasing surface densities of RGD which resulted in both increased cell attachment and the promotion of a tri phasic proliferative response of a human corneal epithelial cell line (hTCEpi). The ability to treat PEI/PVDMA films with peptides for controlled cell-substrate interactions enables the use of these films in a wide range of biological applications. PMID- 21972076 TI - Determination of cranio-spinal canal compliance distribution by MRI: Methodology and early application in idiopathic intracranial hypertension. AB - PURPOSE: To develop a method for derivation of the cranial-spinal compliance distribution, assess its reliability, and apply to obese female patients with a diagnosis of idiopathic intracranial hypertension (IIH). MATERIALS AND METHODS: Phase contrast-based measurements of blood and cerebrospinal fluid (CSF) flows to, from, and between the cranial and spinal canal compartments were used with lumped-parameter modeling to estimate systolic volume and pressure changes from which cranial and spinal compliance indices are obtained. The proposed MRI indices are analogous to pressure volume indices (PVI) currently being measured invasively with infusion-based techniques. The consistency of the proposed method was assessed using MRI data from seven aged healthy subjects. Measurement reproducibility was assessed using five repeated MR scans from one subject. The method was then applied to compare spinal canal compliance contribution in seven IIH patients and six matched healthy controls. RESULTS: In the healthy subjects, as expected, spinal canal contribution was consistently larger than the cranial contribution (average value of 69%). Measurement variability was 8%. In IIH, the spinal canal contribution is significantly smaller than normal controls (60 versus 78%, P < 0.03). CONCLUSION: An MRI-based method for derivation of compliance indices analogous to PVI has been implemented and applied to healthy subjects. The application of the method to obese IIH patients suggests a spinal canal involvement in the pathophysiology of IIH. PMID- 21972077 TI - Molecular imaging of inflammation and carcinogenesis. AB - Development of imaging agents that can be used broadly for early detection of neoplasia at various tissue sites and at various stages of disease and that also can assess states of minimal residual disease would have tremendous utility in the diagnosis and management of cancer. In a series of articles culminating with a report in this issue of the journal (beginning on page 1536), Uddin and colleagues show their ability to systemically target the enzyme COX-2 with imaging probes that will serve as agents for early detection, risk assessment, prognosis, and intervention outcome measures. These probes will enable the detection and localization of regions of inflammation and a wide variety of premalignant lesions and cancers, with utility in monitoring the effects of cancer prevention and therapy. PMID- 21972078 TI - Alu in Lynch syndrome: a danger SINE? AB - Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline loss of a DNA mismatch repair gene. In a significant proportion of cases, loss of function of the MSH2 mismatch repair gene is caused by large heterogeneous deletions involving MSH2 and/or the adjacent EPCAM gene. These deletions usually result from homologous malrecombination events between Alu elements, a family of short interspersed nuclear elements (SINE). Recent recognition that the extent of these deletions influences phenotypic outcome provided new impetus for fine mapping the breakpoints. In doing so, Perez-Cabornero and colleagues uncovered new evidence for Alu-mediated ancestral founder deletions within MSH2 in the Spanish Lynch syndrome population (as reported beginning on pages 1546 and 1556 in this issue of the journal). This is the first such finding to date and prompted a revisitation of the role of Alu elements in the causation of Lynch syndrome. Whether Alu density is a danger sign for genomic regions prone to rearrangement and what additional factors may be required to actuate these events remain to be discovered. PMID- 21972079 TI - Examining stools for colon cancer prevention: what are we really looking for? AB - Fecal immunochemical testing (FIT) is superior to guiac-based testing if we are looking for blood in stools, as it has better one-time colorectal cancer sensitivity and specificity and better patient acceptance. In this issue of the journal, Cai and colleagues (beginning on page 1572) and Khalid-de Bakker and colleagues (beginning on page 1563) present new information about the one-time test performance of FIT. FIT will have a growing appeal to providers and health care systems as resources for clinical preventive services shrink and as incentives to expand colorectal screening rates increase, but there are good reasons to be cautious about the temptation to organize new FIT screening programs. Colorectal screening has two potential objectives: To find cancers in an earlier, more-treatable stage and to find and remove adenomas to prevent cancers from forming in the first place. Because most adenomas, even advanced adenomas, do not bleed, tests designed to identify occult blood in the stool are better for detecting colorectal cancer, whereas direct endoscopic visualization of the colorectum is better for prevention. Even if advanced adenomas did commonly bleed, low compliance with repeat annual testing will seriously erode the benefit of FIT. PMID- 21972080 TI - The origin of intestinal stem cells in Drosophila. AB - Renewing tissues in the adult organism such as the gastrointestinal (GI) epithelium depend on stem cells for epithelial maintenance and repair. Yet, little is known about the developmental origins of adult stem cells and their niches. Studies of Drosophila adult midgut precursors (AMPs), a population of endodermal progenitors, demonstrate that adult intestinal stem cells (ISCs) arise from the AMP lineage and provide insight into the stepwise process by which the adult midgut epithelium is established during development. Here, I review the current literature on AMPs, where local, inductive and long-range humoral signals have been found to control progenitor cell behavior. Future studies will be necessary to determine the precise mechanism by which adult intestinal stem cells are established in the endodermal lineage. PMID- 21972081 TI - Wild Mediterranean dietary plants as inhibitors of pancreatic lipase. AB - Lipids are essential compounds for all living organisms. Agents that inhibit fat digestion are of theoretical benefit in the treatment of obesity. A total of 18 species (21 hydroalcoholic extracts) of edible plants from Calabria region (Italy) were evaluated for their in vitro pancreatic lipase inhibitory activity. Lipase activity was measured by monitoring the hydrolysis of p-NPC, which releases the yellow chromogen, p-nitrophenol. The aqueous ethanol extracts of Portulaca oleracea (leaves) and Silene vulgaris (leaves) exhibited the strongest inhibitory effect on lipase. The amounts of total phenolics, measured by Folin Ciocalteu method, varied widely in the different analysed extracts and ranged from 29 to 482 mg/g of extract. In this study, the findings do not show any relationship between lipase inhibitory activity and total phenolic content. PMID- 21972082 TI - Liver X receptors regulate cholesterol homeostasis in oligodendrocytes. AB - Cholesterol synthesis and transport in oligodendrocytes are essential for optimal myelination and remyelination in pathological conditions such as multiple sclerosis. However, little is known about cholesterol homeostasis in the myelin forming oligodendrocytes. Liver X receptors (LXRs) are nuclear oxysterol receptors that regulate genes involved in cholesterol homeostasis and may therefore play an important role in de- and remyelination. We investigated whether LXRs regulate cholesterol homeostasis in oligodendrocytes. mRNA expression of genes encoding LXR-alpha and LXR-beta and their target genes (ABCA1, ABCG1, ABCG4, apoE, and LDLR) was detected in oligodendrocytes derived from both neonatal and adult rats using quantitative real-time PCR. The expression of LXR-beta and several target genes was increased during oligodendrocyte differentiation. We further demonstrated that treatment of primary neonatal rat oligodendrocytes with the synthetic LXR agonist T0901317 induced the expression of several established LXR target genes, including ABCA1, ABCG1, apoE, and LDLR. Treatment of oligodendrocytes with T0901317 resulted in an enhanced cholesterol efflux in the presence of apolipoprotein A-I or high-density lipoprotein particles. These data show that LXRs are involved in regulating cholesterol homeostasis in oligodendrocytes. PMID- 21972083 TI - Seasonal suitability of three rubber tree clones to Calacarus heveae (Acari, Eriophyidae). AB - The suitability of rubber tree clones to Calacarus heveae was inferred from the life cycle, reproduction and survivorship of this mite. The assays were performed under controlled conditions with leaflets detached from 6-year-old plants. The development of 20 C. heveae individuals on each of the clones GT 1, PB 235 and RRIM 600 was analysed. This experiment was performed four times during periods when C. heveae was abundant in the field: (P1) November-December 2005, (P2) January-February, (P3) March-April and (P4) May-June 2006. Accordingly, the leaflets used in each assay represented the physiological condition of the host plant during each period. This approach allowed us to evaluate the seasonal suitability of rubber tree clones to C. heveae. We observed seasonal differences in the suitability of rubber tree clones to mite attack. The mites reared on the PB235 had a shorter development period, the highest egg production and highest survivorship. This evidence showed that the PB 235 was the most suitable of those tested. We also observed that the leaflets used in the assays during periods P2 and P3 were the most favourable for the development of C. heveae. This finding emphasises the seasonal suitability of rubber tree leaflets. On the other hand, GT 1 showed higher resistance against C. heveae than did RRIM 600 and PB 235, primarily during the period from November to February. This result indicated that use of the GT 1 clone to control the mite might represent an alternative for growers. PMID- 21972084 TI - A review of the natural enemies of the red palm mite, Raoiella indica (Acari: Tenuipalpidae). AB - A review of all the available information about the natural enemies reported in association with the red palm mite, Raoiella indica is presented. Twenty-eight species of predatory arthropods, including mites and insects, have been reported in association with R. indica in Asia, Africa and the Neotropics. In addition, pathogenic fungi associated with R. indica in the Caribbean have been reported. The available literature indicates that each site has a different natural enemy complex with only one predator species, Amblyseius largoensis (Acari: Phytoseiidae), present in all the geographical areas. The phytoseiids, Amblyseius caudatus Berlese, Amblyseius channabasavanni Gupta and A. largoensis, were regarded as important natural enemies of R. indica, and their predatory efficiency was studied in some detail. Among the predatory insects the coccinellids Stethorus keralicus Kapur and Telsimia ephippiger Chapin were reported as major predators of R. indica. The known distribution, abundance and relative importance of each species reported in association with R. indica are discussed. PMID- 21972085 TI - The case of Do-Not-Resuscitate (DNR) orders and the intellectually disabled patient. AB - In the case of an intellectually disabled patient, the attending physician was restricted from writing a Do-Not-Resuscitate (DNR) order. Although the rationale for this restriction was to protect the patient from an inappropriate quality of life judgment, it resulted in a worse death than the patient would have experienced had he not been disabled. Such restrictions that are intended to protect intellectually disabled patients may violate their right to equal treatment and to a dignified death. PMID- 21972086 TI - Resistance tests and field trials with bromadiolone for the control of Norway rats (Rattus norvegicus) on farms in Westphalia, Germany. AB - BACKGROUND: The aim of this study was to determine the incidence and the level of resistance to bromadiolone among rats on farms suspected of being foci of resistance by using the international normalised ratio (INR)-based blood clotting response (BCR) test. Whether the level of reduced susceptibility constitutes 'practical resistance' was subsequently determined in field trials. RESULTS: The 2.5 multiple of the ED(50) baseline was used to test for the incidence of resistance, and higher multiples in the range of the suspected resistance factor were used to investigate the degree of resistance. The ED(50) values of bromadiolone in resistant rats were confirmed in the range 4.70-7.05 mg kg(-1) for males and 4.62-6.61 mg kg(-1) for females. Variations within these ranges appeared between farms. According to the BCR resistance tests, 50-100% of rats were classified as resistant prior to the field trials; 29-100% of rats survived the treatments. CONCLUSION: BCR tests based on the use of the INR and baselines are suitable for determining the incidence and for assessing the level of resistance in populations of Norway rats. The majority of rats of the Westphalian resistant strain, characterised by the Y139C marker in VKOR, are resistant to bromadiolone under practical control conditions. PMID- 21972087 TI - A mobile Sn nanowire inside a beta-Ga2 O3 tube: a practical nanoscale electrically/thermally driven switch. AB - Nanoelectromechanical system switches are seen as key devices for fast switching in communication networks since they can be switched between transmitting and receiving states with an electrostatic command. Herein, the fabrication of practical, nanoscale electrically/thermally driven switches is reported based on a mobile Sn nanowire inside a beta-Ga2 O3 tube. The melting point of Sn inside the Ga2 O3 tube is found to be as low as 58 degrees C-far below the value of bulk Sn (231.89 degrees C)-and its crystal phase (beta-Sn) remains unchanged even at temperatures as low as -170 degrees C. Thus a miniaturization of the unique wide-temperature-range thermometer based on the linear thermal expansion of liquid Sn fillings in the Ga2 O3 tube is realized. In addition, the electrical properties of the Sn-nanowire-filled beta-Ga2 O3 tubes are carefully determined: importantly, the resistance demonstrates a sudden drop (rise) when two Sn nanowires contact (separate), due to the thermally driven motion of the liquid Sn fillings inside the tube. Thus this structure can be switched between its on and off states by controlling the motion, merging or splitting, of the Sn nanowires inside the tube, either electrically, by applying a current, or thermally, at a predetermined temperature. PMID- 21972088 TI - Expression of the nonclassical HLA-G and HLA-E molecules in laryngeal lesions as biomarkers of tumor invasiveness. AB - INTRODUCTION: HLA-G and HLA-E are two nonclassical class I molecules, which have been well recognized as modulators of innate and adaptive immune responses, and the expression of these molecules in virus infected cells has been associated with subversion of the immune response. OBJECTIVE: In this study we performed a cross-sectional study, systematically comparing the expression of HLA-G and HLA-E in benign, pre-malignant and malignant laryngeal lesions, correlating with demographic and clinical variables and with the presence of high-risk and low risk HPV types. MATERIALS AND METHODS: Laryngeal lesions were collected from 109 patients and stratified into 27 laryngeal papillomas, 17 dysplasias, 10 in situ laryngeal carcinomas, 27 laryngeal carcinomas without metastases, 28 laryngeal carcinomas with metastasis along with their respective draining cervical lymph nodes, and 10 normal larynx specimens. The expression of HLA-G and HLA-E molecules was determined by immunohistochemistry. HPV DNA detection and typing was performed using generic and specific primers. RESULTS: HLA nonclassical molecules showed a distinct distribution pattern, according to the larynx lesion grade. HLA-G expression increased in benign and premalignant lesions, and gradually decreased in invasive carcinomas and in respective draining cervical lymph nodes. Conversely, HLA-E expression increased as far as lesion grade increased, including increased molecule expression in the draining lymph nodes of malignant lesions. Only 17 (15.6%) patients were HPV DNA positive. CONCLUSIONS: Overexpression of HLA-E and underexpression of HLA-G appear to be good markers for malignant larynx lesion. PMID- 21972089 TI - Lymphangiogenic VEGF-C and VEGFR-3 expression in genetically characterised gastrointestinal stromal tumours. AB - This study aimed to assess the distribution of VEGF-C and VEGFR-3 expression in gastrointestinal stromal tumours (GISTs), and to analyse the value of lymphatic vessel density (LVD) in a tumour that is believed to preferentially metastasize through blood vessel conduits. A panel of immunohistochemical antibodies was used to evaluate 51 cases of genetically characterised GISTs: VEGF-C, VEGFR-3, D2-40 (for LVD assessment) and CD31 (for blood vessel density--BDV--assessment). The results were correlated with the clinical-pathological data. The large majority of cases (86.2%; 44/51) showed a mutation of the KIT gene, most of them (72.5%; 37/51) revealing mutations in exon 11. VEGFR-3 was predominantly expressed in KIT mutated GISTs (p=0.019). High LVD was correlated with the absence of metastasis (p=0.010) and high BVD showed a positive correlation with the occurrence of metastasis (p=0.049). The strong expression of VEGF-C and VEGFR-3 in GIST's cells was not correlated with the clinical parameters of aggressiveness, nor with high LVD. PMID- 21972090 TI - Immunohistochemical characterisation of dorsal root ganglia neurons supplying the porcine mammary gland. AB - The present study investigated the chemical coding of mammary gland-projecting dorsal root ganglia (DRG) neurons using double-labelling immunohistochemistry. Earlier investigations revealed the presence of Fast blue - positive (FB+) neurons in Th9-Th12 DRG after injection of the tracer into the second, right thoracic mamma. Neurons projecting to the last right abdominal mamma were found in L1-L3 DRG. In the present study, the cryostat sections from these ganglia were stained for calcitonin gene-related peptide (CGRP), substance P (SP), nitric oxide synthase (NOS), galanin (GAL) and pituitary adenylate cyclase activating polypeptide (PACAP). Immunohistochemistry revealed that the vast majority of FB+ mammary gland-projecting neurons contained immunoreactivity to CGRP (68.87+/ 0.7%), SP (63.4+/-0.9%), NOS (32.47+/-0.9%), GAL (16.28+/-0.8%) and less numerous nerve cells stained for PACAP (5.87+/-0.5%). The present results largely correspond with findings dealing with immunohistochemical characterization of nerve fibres supplying porcine mammary gland structures described earlier. PMID- 21972091 TI - An experimental type II mixed cryoglobulinemia with renal glomerulopathy in ICR mice triggered by Capillaria hepatica infection. AB - Type II mixed cryoglobulinemia is characterized by systemic vasculitis with deposition of cryoprecipitatable-immunoglobulins containing rheumatoid factor. Pathogenesis of type II mixed cryoglobulinemia has not yet been completely clarified because of the lack of an experimental animal. Here, we report an animal model of type II mixed cryoglobulinemia that is induced by experimental infection with Capillaria hepatica in ICR mice. Capillaria hepatica is a nematode that causes necrotic hepatitis in several mammals. In this study, mice experimentally infected with C. hepatica eggs developed cryoglobulinemia at 20 and 30 days post injection. Using immunological analysis, cryoglobulinemia in infected mice was classified as type II mixed cryoglobulinemia by detection of monoclonal IgM rheumatoid factor and IgA in the cryoprecipitate of serum. Using immunofluorescence, we observed an increase in the number of double-positive cells for u heavy and kappa light chains of immunoglobulin in the spleens of infected mice. Histopathologically, this model was characterized by glomerulopathy associated with intense deposition of IgM and IgA filling in capillary lumina. Ultrastructural analysis showed that glomerular deposits consisted of stacks of twisted microtubular structures. These serological and histological features resembled those of type II mixed cryoglobulinemia in human. This is the first experimental animal model of type II mixed cryoglobulinemia that will enable detailed studies on the pathogenesis of cryoglobulinemia. PMID- 21972092 TI - PTPIP51, a positive modulator of the MAPK/Erk pathway, is upregulated in glioblastoma and interacts with 14-3-3beta and PTP1B in situ. AB - Glioblastoma multiforme (GBM) is the most common and most malignant primary brain tumour. Protein tyrosine phosphatase interacting protein 51 (PTPIP51) is an interaction partner of 14-3-3beta, which correlates with the grade of malignancy in gliomas. In this study PTPIP51 and its interacting partners 14-3-3beta, PTP1B, c-Src, Raf-1 as well as EGFR were investigated in human glioblastoma. Twenty glioblastoma samples were analyzed on transcriptional and translational level by immunohistochemistry, in situ hybridization and RT-PCR. To compare PTPIP51 expression in gliomas of different malignancies, quantitative RT-PCR for grade II astrocytoma and GBM samples was employed. Additionally, we analyzed the correlation between PTPIP51 and 14-3-3beta transcription, and checked for in situ interaction between PTPIP51 and 14-3-3beta and PTP1B, respectively. PTPIP51 and 14-3-3beta mRNA showed a tumour grade dependent upregulation in gliomas. Glioblastoma cells displayed a strong immunoreaction of PTPIP51, which co localized with 14-3-3beta and PTP1B. The duolink proximity ligation assay corroborated a direct in situ interaction of PTPIP51 with both proteins, known to interact with PTPIP51 in vitro. The in vitro interacting partners Raf-1 and c-Src showed a partial co-localization. Besides, immune cells located in capillaries or infiltrating the tumour tissue and endothelial cells of pseudoglomerular vessels revealed a high PTPIP51 expression. The upregulation of PTPIP51 and its connection with the EGFR/MAPK pathway by 14-3-3beta via Raf-1 and by PTP1B via c Src, argue for a functional role of PTPIP51 in the pathogenesis of human glioblastoma. PMID- 21972093 TI - PGC-1alpha and FOXO1 mRNA levels and fiber characteristics of the soleus and plantaris muscles in rats after hindlimb unloading. AB - Fifteen-week-old rats were subjected to unloading induced by hindlimb suspension for 3 weeks. The peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) and forkhead box-containing protein O1 (FOXO1) mRNA levels and fiber profiles of the soleus and plantaris muscles in rats subjected to unloading (unloaded group) were determined and compared with those of age-matched control rats (control group). The body weight and both the soleus and plantaris muscle weights were lower in the unloaded group than in the control group. The PGC-1alpha mRNA was downregulated in the soleus, but not in the plantaris muscle of the unloaded group. The FOXO1 mRNA was upregulated in both the soleus and plantaris muscles of the unloaded group. The oxidative enzyme activity was reduced in the soleus, but not in the plantaris muscle of the unloaded group. The percentage of type I fibers was decreased and the percentages of type IIA and IIC fibers were increased in the soleus muscle of the unloaded group, whereas there was no change in fiber type distribution in the plantaris muscle of the unloaded group. Atrophy of all types of fibers was observed in both the soleus and plantaris muscles of the unloaded group. We conclude that decreased oxidative capacity and fiber atrophy in unloaded skeletal muscles are associated with decreased PGC-1alpha and increased FOXO1 mRNA levels. PMID- 21972094 TI - Expression of histone deacetylases 1, 2 and 3 in histological subtypes of testicular germ cell tumours. AB - In this study we aimed to evaluate the protein expression of class I histone deacetylases (HDAC) in testicular germ cell tumours (GCT) and to analyse differences between the histological subtypes of testicular GCT. 325 testicular GCT were included in a tissue microarray with each histological subtype of the tumour being separately represented on this array. Expression of class I HDAC isoforms 1, 2 and 3 was assessed by immunohistochemistry. While HDAC2 and 3 were highly expressed in all histological subtypes of GCT, HDAC1 was almost consistently expressed at lower levels. We observed significant differences in the expression of the respective HDACs between seminoma and non-seminoma GCT tissue components. Interestingly, choriocarcinomas showed generally high expression values for all three class I HDAC isoforms. Relevant correlations with clinicopathological parameters could not be demonstrated. Contrasting published findings on other tumour entities, no immediate practical diagnostic or prognostic value for HDAC1-3 in GCT could be inferred. However, the high expression levels might still be indicative for a treatment response to HDAC inhibitors which ought to be evaluated in further studies. PMID- 21972095 TI - Expression of keratin 19, Na-K-Cl cotransporter and estrogen receptor alpha in developing mammary glands of ewes. AB - Mammary gland remodelling is strictly related to intracellular signals and stem cell biology. Among the best candidates to identify the nature and development of mammary cells are cytokeratin 19 (CK19), the Na-K-Cl cotransporter (NKCC1) and receptor of estrogen alpha (ERalpha). In this study, we analyzed the expression of these genes in ewe mammary glands from prepubertal stage to involution. Using Real time PCR we showed that NKCC1 transcription was significantly down regulated during lactation and at involution in comparison to the expression measured in the prepubertal group. No significant differences were found in CK19 expression, whereas ERalpha transcription was significantly down regulated before lambing, during lactation and at involution. In situ hybridization analysis confirmed quantitative data and localized the CK 19 transcript at basal and luminal compartment of terminal ductal unit (TDU) of prepubertal mammary glands. NKCC1 expression was also present in lactating glands and ERalpha in connective tissue surrounding TDU. The characterization and identification of mammary developmental markers in the tissue of dairy animals is necessary to gain knowledge in mammary gland biology. PMID- 21972096 TI - Viability of maxillary bone harvesting by using different osteotomy techniques. A pilot study. AB - The use of autogenous grafts is still considered in bone regeneration surgeries. However, the bone cell viability of such grafts after being harvested from donor sites remains a matter of debate. The aim of the present study is to evaluate particulated and block bone cell viability, in terms of presence or absence of apoptosis and necrosis, obtained from different maxillary intra-oral harvesting methods: bone scraper, rotary carbide burs and piezoelectric device. Five healthy patients were enrolled in the study. The patients required sinus augmentation by lateral window approach. The bone was harvested by the bone scraper, piezoelectric device and rotary surgical instrument. The samples were processed with the Annexin V/FITC (fluorescein isothiocyanate stain) kit and were analyzed by means of Fluoresence-Activated Cell Sorted (FACS) technique. Within the limitations of this pilot study, the results indicated that autogenous bone chips collected from the three harvesting methods presented a large percentage of apoptotic cells, although large scale production of necrotic cells was not detected. In summary, although rotary surgical instrument and piezoelectric devices are frequently used instruments for oral osteotomy, fresh autogenous bone chips collected from them did not present a viable bone cell source. PMID- 21972097 TI - De- and remyelination in the CNS white and grey matter induced by cuprizone: the old, the new, and the unexpected. AB - The copper chelator cuprizone (bis-cyclohexanone oxaldihydrazone) was established as a neurotoxin in rodents in 1966 by Carlton. During the following years the usefulness of cuprizone feeding in mice to induce oligodendrocyte death with secondary demyelination of the superior cerebellar peduncles was described by Blakemore. In 1998 the cuprizone model experienced a renaissance as the group of Matsushima described the effects of cuprizone on the white matter of the cerebrum and focussed on demyelination in the corpus callosum, where the extent of demyelination could be scored more easily and consistently. Since then the toxic cuprizone model has been widely used to study experimental de- and remyelination in the corpus callosum. Recently, we and others have extended these studies and have shown several new aspects characteristic for this model. Many lessons can be learned from these recent findings that have implications for the basic understanding of remyelination and the design of remyelinating and neuroprotective strategies in demyelinating diseases of the CNS. Although the model is often mentioned in the context of multiple sclerosis, it must always be kept in mind that this model has a fundamentally different induction of demyelination. We highlight the important findings delineated from this model and critically discuss both the advantages and the shortcomings of cuprizone induced demyelination. PMID- 21972098 TI - Mechanisms and consequences of hypertriglyceridemia and cellular lipid accumulation in chronic kidney disease and metabolic syndrome. AB - Hypertriglyceridemia and intracellular lipid overload are commonly present in both the chronic kidney disease (CKD) and metabolic syndrome. Hypertriglyceridemia in the metabolic syndrome arises mostly from increased lipoprotein synthesis, while that in the CKD is mainly caused by decreased catabolism. In metabolic syndrome, enhanced plasma levels of free fatty acids and triglyceride (TG) may lead to intracellular fatty acid accumulation in the kidney. However, the mechanisms by which intracellular lipid accumulation occurs in the dieased glomeruli have not been established. I provide evidence that binding/uptake of TG-rich very low-density lipoprotein by glomerular cells is increased in CKD, leading to increased endocytic accumulation of TG. I also provide evidence that cellular damage by fatty acid accumulation in the kidney is particularly severe in podocytes, leading to apoptosis and resulting in glomerulosclerosis. Collectively, these data bring new mechanistic insights into cellular lipid overload and lipotoxicity in CKD. PMID- 21972099 TI - APP transgenic mice and their application to drug discovery. AB - The development of transgenic mice expressing mutated forms of the human amyloid precursor protein (APP) and presenilin-1 (PS1), proteins associated with familial forms of Alzheimer's disease (AD), has provided a backbone for translational studies of potential novel drug therapies. Such mice model some aspects of AD pathology in that they develop senile plaque-like deposits of the amyloid beta protein (Abeta) together with inflammatory pathology and some degree of neurodegeneration. Abeta deposition is considered to be a potentially pathogenic feature of AD and drug discovery programmes utilising such mice and associated with drugs now reaching the clinic have been largely directed towards decreasing the deposition. This goal has been achieved in the mouse models, although the agents developed have not, to date, shown evidence of efficacy in AD sufferers and, in some cases, have worsened the clinical state. Nevertheless, reducing the pathological features of the disease continues to be the objective of pharmacological intervention and ongoing programmes continue to use transgenic mice expressing mutated APP and PS1 transgenes in attempts to overcome issues and difficulties arising from the initial clinical trials and to explore new approaches to AD treatment. PMID- 21972100 TI - Using legacy data to relate biological condition to cumulative aquatic toxicity in the Willamette River Basin (Oregon, USA). AB - In the Willamette River Basin (Oregon, USA), various residential, municipal, industrial, and agricultural activities produce physical, biological, and chemical stressors that may impinge on the basin's aquatic ecosystems. For > 30 years, numerous water-quality and biological-condition data have been accumulated by often disparate monitoring programs. This diagnostic analysis explored whether these legacy data could be used to correlate the presence of chemical stressors with biological condition impacts with the understanding that association is not necessarily causation. Other natural or anthropogenic stressors that may also impact biological conditions were not considered in this study. Acute-toxicity indices were calculated separately for trace metals and organic chemicals detected in surface waters between 1994 and 2010 and then compared with land-use metrics and vertebrate- and invertebrate-assemblage indices from surveys conducted basin-wide during this same period. Half of the possible relations between land use, biological condition, and toxicity were statistically significant at p <= 0.10. These results suggest that conditions for aquatic receptors improve either as agricultural or urban land decreases or as forested land increases and that chemical mixtures (primarily involving pesticides) may have impacted components of the basin's aquatic ecosystems. There may be a need for strengthened chemical-management practices on agricultural and urban lands and for maintaining undisturbed forested land to limit chemical migration into adjacent waters. Although these results indicate some utility for legacy data, they also suggest that a more defensible assessment of chemical stressors requires a program specifically designed for that purpose. PMID- 21972101 TI - Interfacial thermal conductance of transfer-printed metal films. PMID- 21972102 TI - Standardized extracts of Bacopa monniera protect against MPP+- and paraquat induced toxicity by modulating mitochondrial activities, proteasomal functions, and redox pathways. AB - Parkinson's disease (PD) is one of the most common age-related neurodegenerative diseases and affects millions of people worldwide. Strong evidence supports the role of free radicals, oxidative stress, mitochondrial, and proteasomal dysfunctions underlying neuronal death in PD. Environmental factors, especially pesticides, represent one of the primary classes of neurotoxic agents associated with PD, and several epidemiological studies have identified the exposure of the herbicide paraquat (PQ) as a potential risk factor for the onset of PD. The objective of our study was to investigate the neuroprotective effects of the standardized extracts of Bacopa monniera (BM) against PQ-induced and 1-methyl-4 phenyl-pyridinium iodide (MPP(+))-induced toxicities and to elucidate the mechanisms underlying this protection. Our results show that a pretreatment with the BM extract from 50 MUg/ml protected the dopaminergic SK-N-SH cell line against MPP(+)- and PQ-induced toxicities in various cell survival assays. We demonstrate that BM pretreatment prevented the depletion of glutathione (GSH) besides preserving the mitochondrial membrane potential and maintaining the mitochondrial complex I activity. BM pretreatment from 10.0 MUg/ml also prevented the generation of intracellular reactive oxygen species and decreased the mitochondrial superoxide level. BM treatment activated the nuclear factor erythroid 2-related factor 2 pathway by modulating the expression of Keap1, thereby upregulating the endogenous GSH synthesis. The effect of BM on the phosphorylation of Akt further strengthens its role in the promotion of cell survival. By preserving the cellular redox homeostasis and mitochondrial activities and by promoting cell survival pathways, BM extract may have therapeutic uses in various age-related neurodegenerative diseases such as PD. PMID- 21972103 TI - Air-liquid biofilm formation is dependent on ammonium depletion in a Saccharomyces cerevisiae flor strain. AB - Air-liquid biofilm formation appears to be an adaptive mechanism that promotes foraging of Saccharomyces cerevisiae flor strains in response to nutrient starvation. The FLO11 gene plays a central role in this phenotype as its expression allows yeast cells to rise to the liquid surface. Here, we investigated the role of ammonium depletion in air-liquid biofilm formation and FLO11 expression in a S. cerevisiae flor strain. The data obtained show that increasing ammonium concentrations from 0 to 450 m m reduce air-liquid biofilm in terms of biomass and velum formation and correlate with a reduction of FLO11 expression. Rapamycin inhibition of the TOR pathway and deletion of RAS2 gene significantly reduced biofilm formation and FLO11 expression. Taken together, these data suggest that ammonium depletion is a key factor in the induction of air-liquid biofilm formation and FLO11 expression in S. cerevisiae flor strains. PMID- 21972104 TI - Urolithin as a converging scaffold linking ellagic acid and coumarin analogues: design of potent protein kinase CK2 inhibitors. AB - Casein kinase 2 (CK2) is a ubiquitous, essential, and highly pleiotropic protein kinase; its abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and other relevant diseases. Previously, using different in silico screening approaches, two potent and selective CK2 inhibitors were identified by our group: ellagic acid, a naturally occurring tannic acid derivative (K(i)=20 nM) and 3,8-dibromo-7-hydroxy-4-methylchromen-2-one (DBC, K(i)=60 nM). Comparing the crystallographic binding modes of both ellagic acid and DBC, an X-ray structure-driven merging approach was taken to design novel CK2 inhibitors with improved target affinity. A urolithin moiety is proposed as a possible bridging scaffold between the two known CK2 inhibitors, ellagic acid and DBC. Optimization of urolithin A as the bridging moiety led to the identification of 4-bromo-3,8-dihydroxy-benzo[c]chromen-6-one as a novel, potent and selective CK2 inhibitor, which shows a K(i) value of 7 nM against the protein kinase, representing a significant improvement in affinity for the target compared with the two parent fragments. PMID- 21972106 TI - Pain as an important predictor of psychosocial health in patients with rheumatoid arthritis. AB - OBJECTIVE: To examine the evolution of psychosocial aspects of health-related quality of life in rheumatoid arthritis (RA) patients, and to identify their predictors. METHODS: All patients within a Swiss RA cohort and a US RA cohort who completed a Short Form 36 (SF-36) scale at least twice within a 4-year period were included. The primary outcome was psychosocial health as measured by the mental component summary (MCS) score of the SF-36. The evolution of this outcome over time was analyzed using structural equation models, which distinguish between the stable, the variable, and the measurement error components of the outcome's variance. RESULTS: A total of 15,282 patients (48,323 observations) were included. MCS scores were mostly stable over time (between 69% and 75% of the variance was not due to measurement error). The variable component of the SF 36 was mostly due to fluctuations at the moment of measurement and not to a global time trend of psychosocial health. Pain was the most important predictor of both the stable and variable components of psychosocial health, explaining ~44% of the observed psychosocial health variance. CONCLUSION: This large cohort study demonstrates that pain is the most important predictor of a patient's psychosocial health in RA patients. This suggests that physicians should place greater emphasis on pain management. PMID- 21972105 TI - An MDR1 promoter allele with higher promoter activity is common in clinically isolated strains of Candida albicans. AB - In the opportunistic fungal pathogen Candida albicans, up-regulation of MDR1, encoding an efflux transporter, leads to increased resistance to the antifungal drug fluconazole. Antifungal resistance has been linked to several types of genetic change in C. albicans, including changes in genome structure, genetic alteration of the drug target, and overexpression of transporters. High-level over-expression of MDR1 is commonly mediated by mutation in a trans-acting factor, Mrr1p. This report describes a second mechanism that contributes to up regulation of MDR1 expression. By analyzing the sequence of the MDR1 promoter region in fluconazole-resistant and fluconazole-susceptible strains, we identified sequence polymorphisms that defined two linkage groups, corresponding to the two alleles in the diploid genome. One of the alleles conferred higher MDR1 expression compared with the other allele. Strains in which both alleles were of the higher activity type were common in collections of clinically isolated strains while strains carrying only the less active allele were rare. As increased expression of MDR1 confers higher resistance to drugs, strains with the more active MDR1 promoter allele may grow or survive longer when exposed to drugs or other selective pressures, providing greater opportunity for mutations that confer high-level drug resistance to arise. Through this mechanism, higher activity alleles of the MDR1 promoter could promote the development of drug resistance. PMID- 21972107 TI - Hierarchical titanium surface textures affect osteoblastic functions. AB - This study investigated the surface characteristics and in vitro cytocompatibility of hierarchical textured titanium surfaces with nanograins and microroughness, produced by surface mechanical attrition treatment (SMAT). The surface characteristics were evaluated by scanning electron microscopy, X-ray diffraction, transmission electron microscopy, contact angle, and surface energy measurements. The in vitro cytocompatibility of the SMAT processed surfaces (hereafter Ti-SMAT surfaces) were assessed in terms of cellular attachment, morphology, viability, alkaline phosphatase (ALP) activity, and mRNA gene expression. Two other titanium surfaces were compared: well-polished Ti6Al4V surfaces (hereafter Ti-polish surfaces) and thermally sprayed rough surfaces (hereafter Ti-spray surfaces). The Ti-SMAT surfaces showed a higher hydrophilicity and increased surface energy compared with the Ti-polish and Ti spray surfaces. Consequently, these Ti-SMAT surfaces demonstrated enhancement of cell attachment, spreading, viability, and ALP activity. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis showed significantly higher ALP activity and stronger expression of mRNA levels of key osteoblast genes in cells grown on the Ti-SMAT surfaces than the other two surfaces. These results reveal a synergic role played by nanostructure and microtopography in osteoblastic functions and demonstrate the more promising cytocompatibility of the hierarchical textured surfaces. It is suggested that the SMAT process may provide a novel method of surface modification to the currently available metallic biomaterials. PMID- 21972108 TI - Three-dimensional late gadolinium enhancement imaging of the left atrium with a hybrid radial acquisition and compressed sensing. AB - PURPOSE: To develop and test a hybrid radial (stack of stars) acquisition and compressed sensing reconstruction for efficient late gadolinium enhancement (LGE) imaging of the left atrium. MATERIALS AND METHODS: Two hybrid radial acquisition schemes, kx-ky-first and kz-first, are tested using the signal equation for an inversion recovery sequence with simulated data. Undersampled data reconstructions are then performed using a compressed sensing approach with a three-dimensional total variation constraint. The data acquisition and reconstruction framework is tested on five atrial fibrillation patients after treatment by radio-frequency ablation. The hybrid radial data are acquired with free breathing without respiratory navigation. RESULTS: The kz-first radial acquisition gave improved image quality as compared to a kx-ky-first scheme. Compressed sensing reconstructions improved the overall quality of undersampled radial LGE images. An image quality metric that takes into account the signal, noise, artifact, and blur for the radial images was 35% (+/-17%) higher than the corresponding Cartesian acquisitions. Total acquisition time for 36 slices with 1.25 * 1.25 * 2.5 mm(3) resolution was under 3 min for the proposed scheme. CONCLUSION: Hybrid radial LGE imaging of the LA with compressed sensing is a promising approach for obtaining images efficiently and offers more robust image quality than Cartesian acquisitions that were acquired without a respiratory navigator signal. PMID- 21972109 TI - Germline gain-of-function mutations of ALK disrupt central nervous system development. AB - Neuroblastoma (NB) is a frequent embryonal tumor of sympathetic ganglia and adrenals with extremely variable outcome. Recently, somatic amplification and gain-of-function mutations of the anaplastic lymphoma receptor tyrosine kinase (ALK) gene, either somatic or germline, were identified in a significant proportion of NB cases. Here we report a novel syndromic presentation associating congenital NB with severe encephalopathy and abnormal shape of the brainstem on brain MRI in two unrelated sporadic cases harboring de novo, germline, heterozygous ALK gene mutations. Both mutations are gain-of-function mutations that have been reported in NB and NB cell lines. These observations further illustrate the role of oncogenes in both tumour predisposition and normal development, and shed light on the pleiotropic and activity-dependent role of ALK in humans. More generally, missing germline mutations relative to the spectrum of somatic mutations reported for a given oncogene may be a reflection of severe effects during embryonic development, and may prompt mutation screening in patients with extreme phenotypes. PMID- 21972110 TI - NSD1 PHD domains bind methylated H3K4 and H3K9 using interactions disrupted by point mutations in human sotos syndrome. AB - Sotos syndrome is a human developmental and cognitive disorder caused by happloinsufficiency of transcription factor NSD1. Similar phenotypes arise from NSD1 gene deletion or from point mutations in 9 of 13 NSD1 domains, including all 6 PHD domains, indicating that each NSD1 domain performs an essential role. To gain insight into the biochemical basis of Sotos syndrome, we tested the ability of each NSD1 PHD domain to bind histone H3 when methylated at regulatory sites Lys4, Lys9, Lys27, Lys36, and Lys79, and histone H4 at regulatory Lys20, and determined whether Sotos point mutations disrupted methylation site-specific binding. NSD1 PHD domains 1, 4, 5, and 6 bound histone H3 methylated at Lys4 or Lys9. Eleven of 12 Sotos mutations in PHD4, PHD5, and PHD6 disrupted binding to these methylated lysines, and 8 of 9 mutations in PHD4 and PHD6 severely compromised binding to transcription cofactor Nizp1. One mutation in PHD1 did not alter binding to specific methylated histone H3, and one mutation in PHD4 did not alter binding to either methylated histone or Nizp1. Our data suggests that Sotos point mutations in NSD1 PHD domains disrupt its transcriptional regulation by interfering with its ability to bind epigenetic marks and recruit cofactors. PMID- 21972112 TI - A novel mutation in CRYBB1 associated with congenital cataract-microcornea syndrome: the p.Ser129Arg mutation destabilizes the betaB1/betaA3-crystallin heteromer but not the betaB1-crystallin homomer. AB - Congenital cataract-microcornea syndrome (CCMC) is a clinically and genetically heterogeneous condition characterized by lens opacities and microcornea. It appears as a distinct phenotype of heritable congenital cataract. Here we report a large Chinese family with autosomal dominant congenital cataract and microcornea. Evidence for linkage was detected at marker D22S1167 (LOD score [Z]=4.49, recombination fraction [theta]=0.0), which closely flanks the a crystallin gene cluster locus. Direct sequencing of the candidate aB1-crystallin gene (CRYBB1) revealed a c.387C>A transversion in exon 4, which cosegregated with the disease in the family and resulted in the substitution of serine by arginine at codon 129 (p.Ser129Arg). A comparison of the biophysical properties of the recombinant beta-crystallins revealed that the mutation impaired the structures of both betaB1-crystallin homomer and betaB1/betaA3-crystallin heteromer. More importantly, the mutation significantly decreased the thermal stability of betaB1/betaA3-crystallin but not betaB1-crystallin. These findings highlight the importance of protein-protein interactions among beta-crystallins in maintaining lens transparency, and provide a novel insight into the molecular mechanism underlying the pathogenesis of human CCMC. PMID- 21972113 TI - New germline syndrome with brainstem abnormalities and neuroblastoma, caused by ALK mutation. PMID- 21972111 TI - Nonsense mutation-associated Becker muscular dystrophy: interplay between exon definition and splicing regulatory elements within the DMD gene. AB - Nonsense mutations are usually predicted to function as null alleles due to premature termination of protein translation. However, nonsense mutations in the DMD gene, encoding the dystrophin protein, have been associated with both the severe Duchenne Muscular Dystrophy (DMD) and milder Becker Muscular Dystrophy (BMD) phenotypes. In a large survey, we identified 243 unique nonsense mutations in the DMD gene, and for 210 of these we could establish definitive phenotypes. We analyzed the reading frame predicted by exons flanking those in which nonsense mutations were found, and present evidence that nonsense mutations resulting in BMD likely do so by inducing exon skipping, confirming that exonic point mutations affecting exon definition have played a significant role in determining phenotype. We present a new model based on the combination of exon definition and intronic splicing regulatory elements for the selective association of BMD nonsense mutations with a subset of DMD exons prone to mutation-induced exon skipping. PMID- 21972114 TI - Decursin, an active compound isolated from Angelica gigas, inhibits fat accumulation, reduces adipocytokine secretion and improves glucose tolerance in mice fed a high-fat diet. AB - Decursin (De), an active component of Angelica gigas, is known to exert anticancer and neuroprotective effects. However, its antiobesity and antidiabetic potential has not yet been investigated. This study evaluated the antiobesity effect of decursin, particularly focusing on its ability to inhibit adipocyte differentiation in 3T3-L1 cells. Decursin treatment resulted in the inhibition of adipocyte differentiation and the expression of fatty acid synthase. The study further investigated these antiobesity effects using mice fed a normal diet (ND), a high-fat diet (HFD) and a HFD plus decursin 200 mg/kg diet (HFD + De) for 7 weeks. Mice administered HFD plus decursin showed a drastic decrease in weight gain, triglyceride content, total cholesterol content and fat size compared with those that received the HFD alone; this was observed despite similar quantities of total food intake. Furthermore, decursin improved glucose tolerance in mice fed a HFD. Finally, administration of decursin along with the HFD significantly reduced the secretion of HFD-induced adipocytokines such as leptin, resistin, IL 6 and MCP-1. These results suggest that decursin might be useful for the treatment of obesity and diabetes. PMID- 21972115 TI - Modulation of tumor necrosis factor related apoptosis-inducing ligand (TRAIL) receptors in a human osteoclast model in vitro. AB - TRAIL (TNF-related apoptosis-inducing ligand) has been shown to induce apoptosis by binding to TRAIL-R1 and -R2 death receptors, but not to TRAIL-R3 or -R4, its decoy receptors that lack the internal death domain. Osteoclasts (Ocs) are sensitive to TRAIL-induced apoptosis, and modulation of these receptors may change Oc sensitivity to TRAIL. Using human Oc cultures, we first investigated the gene expression profile of these receptors (TNFRSF10 -A, -B, -C, -D encoding TRAIL-Rs 1-4) by real time PCR after adding osteotropic factors during the last week of Oc cultures. We observed a significant decrease in the expression of TNFRSF10-A after the addition of TGFbeta, and an increase in that of TNFRSF10-A and -B post-PTH stimulation. Protein expression of TRAIL-R1 and -R3 was upregulated in the presence of MIP-1alpha, but down-regulated in the presence of TGFbeta (R1), TRAIL (R2) or OPG (R3). The percentage of Ocs expressing the TRAIL R1 and/or -R2 at their surface was increased by MIP-1alpha and TRAIL, increased (R2) or decreased (R1) by TGFbeta, and the percentage expressing TRAIL-R3 was increased by MIP-1alpha, TRAIL and RANKL. Although significant, the magnitude of all these changes was of about 10-15%. While a direct correlation between these changes and TRAIL-induced Oc apoptosis was less clear, a protective effect was observed in Ocs that had been treated with OPG, and an additive effect in Ocs pre treated with TRAIL or TGFbeta increased TRAIL sensitivity. PMID- 21972116 TI - Fabrication and characterization of cytocompatible polypyrrole films inkjet printed from nanoformulations cytocompatible, inkjet-printed polypyrrole films. AB - Inkjet printed polypyrrole (PPy) films with good uniformity and conductivity are fabricated from a stable, printable PPy nanodispersion, and the cytocompatability of these platforms is demonstrated using PC12 cells. This novel approach to fabricating PPy electrodes and films for tissue engineering and cell stimulation is particularly useful where microstructures are required. PMID- 21972118 TI - Muller glial cells induce stem cell properties in retinal progenitors in vitro and promote their further differentiation into photoreceptors. AB - Using stem cells to replace lost neurons is a promising strategy for treating retinal neurodegenerative diseases. Among their multiple functions, Muller glial cells are retina stem cells, with a robust regenerative potential in lower vertebrates, which is much more restricted in mammals. In rodents, most retina progenitors exit the cell cycle immediately after birth, differentiate as neurons, and then cannot reenter the cell cycle. Here we demonstrate that, in mixed cultures with Muller glial cells, rat retina progenitor cells expressed stem cell properties, maintained their proliferative potential, and were able to preserve these properties and remain mitotically active after several consecutive passages. Notably, these progenitors retained the capacity to differentiate as photoreceptors, even after successive reseedings. Muller glial cells markedly stimulated differentiation of retina progenitors; these cells initially expressed Crx and then developed as mature photoreceptors that expressed characteristic markers, such as opsin and peripherin. Moreover, they were light responsive, insofar as they decreased their cGMP levels when exposed to light, and they also showed high-affinity glutamate uptake, a characteristic of mature photoreceptors. Our present findings indicate that, in addition to giving rise to new photoreceptors, Muller glial cells might instruct a pool of undifferentiated cells to develop and preserve stem cell characteristics, even after successive reseedings, and then stimulate their differentiation as functional photoreceptors. This complementary mechanism might contribute to enlarge the limited regenerative capacity of mammalian Muller cells. PMID- 21972119 TI - Investigating the phytotoxicity of the graminicide fluazifop-P-butyl against native UK wildflower species. AB - BACKGROUND: The selective graminicide fluazifop-P-butyl is used for the control of grass weeds in dicotyledonous crops, and commonly applied in amenity areas to reduce grass productivity and promote wildflower establishment. However, evidence suggests that fluazifop-P-butyl might also have phytotoxic effects on some non target plants. This study investigates the effects of fluazifop-P-butyl on the emergence, phytotoxicity and above-ground biomass of nine perennial wildflower species and two grass species, following pre- and post-emergent applications at half, full and double label rates in a series of glasshouse experiments. RESULTS: While pre- and post-emergent applications of fluazifop-P-butyl caused reductions in seedling emergence and increased phytotoxicity on native wildflower and grass species, these effects were temporary for the majority of wildflower species tested, and generally only occurred at the double application rate. No differences in biomass were observed at any of the rates, suggesting good selectivity and no long-term effects of fluazifop-P-butyl application on the wildflower species from either pre-emergent or post-emergent applications. CONCLUSION: These results have direct relevance to the management of amenity areas for biodiversity, as they confirm the suitability of these wildflower species for inclusion in seed mixtures where fluazifop-P-butyl is to be applied to control grass productivity. PMID- 21972117 TI - Psychometric study of the Aberrant Behavior Checklist in Fragile X Syndrome and implications for targeted treatment. AB - Animal studies elucidating the neurobiology of fragile X syndrome (FXS) have led to multiple controlled trials in humans, with the Aberrant Behavior Checklist Community (ABC-C) commonly adopted as a primary outcome measure. A multi-site collaboration examined the psychometric properties of the ABC-C in 630 individuals (ages 3-25) with FXS using exploratory and confirmatory factor analysis. Results support a six-factor structure, with one factor unchanged (Inappropriate Speech), four modified (Irritability, Hyperactivity, Lethargy/Withdrawal, and Stereotypy), and a new Social Avoidance factor. A comparison with ABC-C data from individuals with general intellectual disability and a list of commonly endorsed items are also reported. Reformulated ABC-C scores based on this FXS-specific factor structure may provide added outcome measure specificity and sensitivity in FXS clinical trials. PMID- 21972120 TI - Controlling water capture of bioinspired fibers with hump structures. AB - Geometrically engineered thin fibers that feature introduced hump structures similar to wetted spider capture silk greatly improve the adhesive ability to drops than uniform ones, which is attributed to an unusual three-phase contact line that extends axially along the fibers. The hump structures improve the stability of the contact line through a combination of "slope" and "curvature" effects, which creates sufficient capillary adhesion to pin drops. PMID- 21972122 TI - Sophisticated crystal transformation of a coordination polymer into mesoporous monocrystalline Ti-Fe-based oxide with room-temperature ferromagnetic behavior. PMID- 21972121 TI - Associations between common variants in GC and DHCR7/NADSYN1 and vitamin D concentration in Chinese Hans. AB - Recent studies have identified common variants in or near GC, CYP2R1 and NADSYN1/DHCR7 to be associated with 25-hydroxyvitamin D [25(OH)D] levels in European populations. We aimed to examine whether these variants also influence 25(OH)D levels in Chinese. Seven common variants were successfully genotyped and tested for associations with plasma 25(OH)D levels in a population-based cohort of 3,210 Chinese Hans from Beijing and Shanghai. Six common variants at GC (rs4588, rs7041, rs2282679 and rs1155563) and NADSYN1/DHCR7 (rs3829251 and rs1790349) loci were all significantly associated with lower plasma 25(OH)D levels (-0.036 <= beta <= -0.076 per risk-allele, P <= 5.7 * 10(-5)), while CYP2R1-rs2060793 showed a trend toward association with 25(OH)D levels in the Shanghai subpopulation (P = 0.08), but not in the Beijing subpopulation (P = 0.82). Haplotype-based association analyses of the four GC variants showed that only the haplotype that contained all risk-alleles (TACC) was significantly associated with lower plasma 25(OH)D levels (beta = -0.085, P = 2.3 * 10(-9)), while the haplotype containing the risk-alleles of rs4588 and rs2282679 (TATC) was marginally associated with lower 25(OH)D levels (beta = -0.054, P = 0.0562) when compared with GCTA haplotype carrying the four protective alleles. Most notably, conditional analyses showed that only GC-rs4588 and GC-rs2282679 (r (2) = 0.97) remained significantly associated with 25(OH)D concentrations (P <= 1.9 * 10(-5)) after adjusting for the other two SNPs in GC. In conclusion, GC and NADSYN1/DHCR7 loci individually and collectively contribute to variation in plasma vitamin D levels in Chinese Hans. PMID- 21972123 TI - Optimizing MR signal contrast of the temporomandibular joint disk. AB - PURPOSE: To use a tissue specific algorithm to numerically optimize UTE sequence parameters to maximize contrast within temporomandibular joint (TMJ) donor tissue. MATERIALS AND METHODS: A TMJ specimen tissue block was sectioned in a true sagittal plane and imaged at 3 Tesla (T) using UTE pulse sequences with dual echo subtraction. The MR tissue properties (PD, T(2) , T(2) *, and T(1) ) were measured and subsequently used to calculate the optimum sequences parameters (repetition time [TR], echo time [TE], and theta). RESULTS: It was found that the main contrast available in the TMJ could be obtained from T(2) (or T(2) *) contrast. With the first echo time fixed at 8 MUs and using TR = 200 ms, the optimum parameters were found to be: theta ~ 60 degrees , and TE2 ~ 15 ms, when the second echo is acquired using a gradient echo and theta ~ 120 degrees , and TE2 ~ 15 ms, when the second echo is acquired using a spin echo. CONCLUSION: Our results show that MR signal contrast can be optimized between tissues in a systematic manner. The MR contrast within the TMJ was successfully optimized with facile delineation between disc and soft tissues. PMID- 21972124 TI - Association of body mass index with symptom severity and quality of life in patients with fibromyalgia. AB - OBJECTIVE: To examine the association between body mass index (BMI) and symptom severity and quality of life (QOL) in patients with fibromyalgia. METHODS: We assessed BMI status and its association with symptom severity and QOL in 888 patients with fibromyalgia who were seen in a fibromyalgia treatment program and who completed the Fibromyalgia Impact Questionnaire (FIQ) and the Short Form 36 (SF-36) health survey. RESULTS: The BMI distribution of nonobese (BMI <25.0 kg/m(2)), overweight (BMI 25.0-29.9 kg/m(2)), moderately obese (BMI 30.0-34.9 kg/m(2)), and severely obese (BMI >=35.0 kg/m(2)) patients was 28.4% (n = 252), 26.8% (n = 238), 22.2% (n = 197), and 22.6% (n = 201), respectively. Age was significantly different among the 4 groups, with those having a greater BMI being older (P = 0.004). After adjustment for age, group differences were significant in the number of tender points (P = 0.003) and the FIQ and SF-36 scores. The groups with the greater BMI had greater fibromyalgia-related symptoms with worse FIQ total scores (P < 0.001), as well as worse scores in the FIQ subscales of physical function (P < 0.001), work missed (P = 0.04), job ability (P = 0.003), pain (P < 0.001), stiffness (P < 0.001), and depression (P = 0.03). These groups also had poorer SF-36 scores in physical functioning (P < 0.001), pain index (P = 0.005), general health perceptions (P = 0.003), role emotional (P = 0.04), and physical component summary (P < 0.001). Post hoc analysis among the 4 groups showed that differences resided primarily in the severely obese group compared with the other groups. CONCLUSION: In patients with fibromyalgia, severe obesity (BMI >=35.0 kg/m(2)) is associated with higher levels of fibromyalgia symptoms and lower levels of QOL. PMID- 21972125 TI - Abbreviations and terminology surrounding autism spectrum disorders and intellectual disability. PMID- 21972127 TI - Solution-based synthesis and design of late transition metal chalcogenide materials for oxygen reduction reaction (ORR). AB - Late transition metal chalcogenide (LTMC) nanomaterials have been introduced as a promising Pt-free oxygen reduction reaction (ORR) electrocatalysts because of their low cost, good ORR activity, high methanol tolerance, and facile synthesis. Herein, an overview on the design and synthesis of LTMC nanomaterials by solution based strategies is presented along with their ORR performances. Current solution based synthetic approaches towards LTMC nanomaterials include a hydrothermal/solvothermal approach, single-source precursor approach, hot injection approach, template-directed soft synthesis, and Kirkendall-effect induced soft synthesis. Although the ORR activity and stability of LTMC nanomaterials are still far from what is needed for practical fuel-cell applications, much enhanced electrocatalytic performance can be expected. Recent advances have emphasized that decorating the surface of the LTMC nanostructures with other functional nanoparticles can lead to much better ORR catalytic activity. It is believed that new synthesis approaches to LTMCs, modification techniques of LTMCs, and LTMCs with desirable morphology, size, composition, and structures are expected to be developed in the future to satisfy the requirements of commercial fuel cells. PMID- 21972128 TI - Combined in vivo multiphoton and CARS imaging of healthy and disease-affected human skin. AB - We present combined epi-coherent anti-Stokes Raman scattering (CARS) and multiphoton imaging with both chemical discrimination and subcellular resolution on human skin in vivo. The combination of both image modalities enables label free imaging of the autofluorescence of endogenous fluorophores by two-photon excited fluorescence, as well as imaging of the distribution of intercellular lipids, topically applied substances and water by CARS. As an example for medical imaging, we investigated healthy and psoriasis-affected human skin with both image modalities in vivo and found indications for different lipid distributions on the cellular level. PMID- 21972126 TI - Telomere maintenance genes SIRT1 and XRCC6 impact age-related decline in telomere length but only SIRT1 is associated with human longevity. AB - Leukocyte telomere length is widely considered a biomarker of human age and in many studies indicative of health or disease. We have obtained quantitative estimates of telomere length from blood leukocytes in a population sample, confirming results of previous studies that telomere length significantly decreases with age. Telomere length was also positively associated with several measures of healthy aging, but this relationship was dependent on age. We screened two genes known to be involved in telomere maintenance for association with the age-related decline in telomere length observed in our population to identify candidate longevity-associated genes. A single-nucleotide polymorphism located in the SIRT1 gene and another in the 3' flanking region of XRCC6 had significant effects on telomere length. At each bi-allelic locus, the minor variant was associated with longer telomeres, though the mode of inheritance fitting best differed between the two genes. No statistical interaction was detected for telomere length between the SIRT1 and XRCC6 variants or between these polymorphisms and age. The SIRT1 locus was significantly associated with longevity (P < 0.003). The frequency of the minor allele was higher in long-lived cases than in young controls, which coincides with the protective role of the minor variant for telomere length. In contrast, the XRCC6 variant was not associated with longevity. Furthermore, it did not affect the association of SIRT1 with exceptional survival. The association of the same variant of SIRT1 with longevity was near significant (P < 0.07) in a second population. These results suggest a potential role of SIRT1 in linking telomere length and longevity. Given the differences between this gene and XRCC6, they point to the distinct impact that alternate pathways of telomere maintenance may have on aging and exceptional survival. PMID- 21972129 TI - Comparative analysis of pesticide action plans in five European countries. AB - BACKGROUND: Denmark, Germany, the Netherlands, France and the United Kingdom have launched national initiatives to reduce pesticide use or risk. Faced with multiple environmental, social and economic constraints such as ensuring the competiveness of European agriculture, the various programmes address goal setting, stakeholder involvement and the role of research and extension in different ways. These diverse experiences offer valuable insights for the development of national action plans required by new European legislation on pesticides. RESULTS: The general trend is to move away from volume or use reduction targets towards reductions in risks and impact. All programmes studied pay attention to involving a wide range of stakeholders in the policy-making process to ensure buy-in. Research and extension services are important players that help to define appropriate goals and improve implementation. Collective approaches to implementation appear to be more effective than the classical linear research-extension-farmer model. CONCLUSION: No matter the approach adopted in fine, member states can gain much from sharing their diverse experience through comparisons such as this study and via international policy seminars which serve as valuable forums for exchange. PMID- 21972130 TI - Strategic applications of Baylis-Hillman adducts to general syntheses of 3 nitroazetidines. AB - A novel one-pot highly diastereoselective synthesis of substituted 3 nitroazetidines via an anionic domino process is described. The synthesis involves a high yielding annulation of Baylis-Hillman alcohols and their aldehydes with either N-aryl/tosylphosphoramidates or N aryl/tosylphosphoramidates in combination with a task-specific ionic liquid [bmim][X-Y] to afford the corresponding 1,2,3-tri- and 1,2,3,4-tetrasubstituted azetidines, respectively. Plausible mechanisms for the formation of various 3 nitroazetidines have been suggested. PMID- 21972131 TI - High-level production of 1,3-propanediol from crude glycerol by Clostridium butyricum AKR102a. AB - The aim of this study was to optimize a biotechnological process for the production of 1,3-propanediol (1,3-PD) based on low-quality crude glycerol derived from biodiesel production. Clostridium butyricum AKR102a was used in fed batch fermentations in 1-L and 200-L scale. The newly discovered strain is characterized by rapid growth, high product tolerance, and the ability to use crude glycerol at the lowest purity directly gained from a biodiesel plant side stream. Using pure glycerol, the strain AKR102 reached 93.7 g/L 1,3-PD with an overall productivity of 3.3 g/(L*h). With crude glycerol under the same conditions, 76.2 g/L 1,3-PD was produced with a productivity of 2.3 g/(L*h). These are among the best results published so far for natural producers. The scale up to 200 L was possible. Due to the simpler process design, only 61.5 g/L 1,3-PD could be reached with a productivity of 2.1 g/(L*h). PMID- 21972132 TI - Characterization of the monoclonal antibody against classical swine fever virus glycoprotein E(rns) and its application to an indirect sandwich ELISA. AB - Classical swine fever virus (CSFV) E(rns) is an envelope glycoprotein possessing RNase activity. The E(rns)-based enzyme-linked immunosorbent assay (ELISA) has been considered a discriminating diagnostic test for differentiating infected from vaccinated animals. The purpose of this study was to produce a specific monoclonal antibody (MAb) to E(rns) for further developing an indirect sandwich ELISA. The MAb CW813 was shown to specifically recognize both the monomer and dimer forms of Pichia pastoris yeast-expressed E(rns) (yE(rns)). The antigenic site recognized by MAb CW813 was mapped to the region of amino acid residues 101 160 of E(rns) where it was neither a neutralizing epitope nor essential to RNase activity. Furthermore, MAb CW813 was utilized as a capture antibody to develop a yE(rns)-based indirect sandwich ELISA for detecting swine antibody to E(rns). The assay demonstrated a high sensitivity and specificity that may provide an alternative method for developing a diagnostic kit with easy manipulation and low cost. PMID- 21972133 TI - Production of cyanophycin in Rhizopus oryzae through the expression of a cyanophycin synthetase encoding gene. AB - Cyanophycin or cyanophycin granule peptide is a protein that results from non ribosomal protein synthesis in microorganisms such as cyanobacteria. The amino acids in cyanophycin can be used as a feedstock in the production of a wide range of chemicals such as acrylonitrile, polyacrylic acid, 1,4-butanediamine, and urea. In this study, an auxotrophic mutant (Rhizopus oryzae M16) of the filamentous fungus R. oryzae 99-880 was selected to express cyanophycin synthetase encoding genes. These genes originated from Synechocystis sp. strain PCC6803, Anabaena sp. strain PCC7120, and a codon optimized version of latter gene. The genes were under control of the pyruvate decarboxylase promoter and terminator elements of R. oryzae. Transformants were generated by the biolistic transformation method. In only two transformants both expressing the cyanophycin synthetase encoding gene from Synechocystis sp. strain PCC6803 was a specific enzyme activity detected of 1.5 mU/mg protein. In one of these transformants was both water-soluble and insoluble cyanophycin detected. The water-soluble fraction formed the major fraction and accounted for 0.5% of the dry weight. The water insoluble CGP was produced in trace amounts. The amino acid composition of the water-soluble form was determined and constitutes of equimolar amounts of arginine and aspartic acid. PMID- 21972134 TI - Tubulin potentiates the interaction of the metalloendopeptidase nardilysin with the neuronal scaffold protein p42IP4/centaurin-alpha1 (ADAP1). AB - We found colocalization of the neuronal protein p42(IP4) (centaurin-alpha1; ArfGAP with dual pleckstrin homology domain [ADAP1]), the metalloendopeptidase nardilysin (NRD; involved in axonal maturation and myelination) and tubulin in the cytosol and at the plasma membrane of SH-SY5Y neuroblastoma cells. To examine the importance of tubulin for the interaction of NRD with p42(IP4), we treated cells with nocodazole, which interferes with tubulin polymerization. Nocodazole did not affect the colocalization of p42(IP4) and tubulin but caused a clear redistribution of the proteins in cells, so that the colocalization of p42(IP4), tubulin and NRD was visible exclusively in multiple foci. To reveal the mechanism of the interaction between NRD, p42(IP4) and tubulin observed in neuronal cells, we performed Far-Western blotting, a technique that directly detects protein protein interactions on Western blots. This technique demonstrated that tubulin enhanced the binding of NRD to functionally renatured p42(IP4). The mutation of a highly conserved cysteine residue in NRD to alanine abolished the potentiation by tubulin. NRD lacking the characteristic acidic domain was able to bind p42(IP4) but addition of tubulin did not significantly potentiate the binding of this deletion mutant to p42(IP4). A function-abolishing mutation of the Zn(2+)-binding motif of NRD did not affect the potentiation by tubulin. Thus, the capacity of tubulin to enhance the interaction between p42(IP4) and NRD together with the known interaction of p42(IP4) with F-actin support the novel notion that p42(IP4) plays a possible role as a linker between the two networks, actin and tubulin, in neural cells. PMID- 21972135 TI - Investigation of lipid composition of dissected sentinel lymph nodes of breast cancer patients by 7T proton MR spectroscopy. AB - PURPOSE: To determine lipid composition of excised healthy and metastatic sentinel lymph nodes of breast cancer patients, as lipids are a potential discriminatory marker for malignancy. MATERIALS AND METHODS: Ten breast cancer patients undergoing surgical nodal staging were included. (1)H-magnetic resonance spectroscopic images (MRSI) were acquired without water and lipid suppression (resolution 3.0 * 3.0 * 5.0 mm(3)). MRSI was compared to histopathology. Six groups of lipid resonances (5.4-5.2, 4.3-4.1, 2.8, 2.3-2.0, 1.6-1.3, 0.9 ppm) were identified. The intensity ratios of the total of these resonances to this total including the water resonance and of each lipid resonance to the total of all lipid resonances were determined. For statistical analysis, a mixed model was applied after logistic transformation. The results were expressed as ratios of the median values of these lipid compositions in metastatic to benign nodes. RESULTS: In all, 6/32 (19%) of the excised nodes contained metastases. The ratios of the lipid resonances 5.4-5.2, 4.3-4.1, 2.8, 2.3-2.0, 1.6-1.3, 0.9 ppm between metastatic vs. benign were 0.3, 1.2, 0.2, 0.2, 1.2, and 0.9, respectively. Only the ratios of signals from unsaturated fatty acids to the total lipid signal differed significantly. CONCLUSION: Metastatic axillary lymph nodes contained fewer unsaturated fatty acids than benign nodes. 7T (1)H-MRS may be useful for detecting axillary breast cancer metastases. PMID- 21972136 TI - Similarities and differences in peripheral blood gene-expression signatures of individuals with schizophrenia and their first-degree biological relatives. AB - Several studies have evaluated the potential utility of blood-based whole transcriptome signatures as a source of biomarkers for schizophrenia. This endeavor has been complicated by the fact that individuals with schizophrenia typically differ from appropriate comparison subjects on more than just the presence of the disorder; for example, individuals with schizophrenia typically receive antipsychotic medications, and have been dealing with the sequelae of this chronic illness for years. The inability to control such factors introduces a considerable degree of uncertainty in the results to date. To overcome this, we performed a blood-based gene-expression profiling study of schizophrenia patients (n = 9) as well as their unmedicated, nonpsychotic, biological siblings (n = 9) and unaffected comparison subjects (n = 12). The unaffected biological siblings, who may harbor some of the genetic predisposition to schizophrenia, exhibited a host of gene-expression differences from unaffected comparison subjects, many of which were shared by their schizophrenic siblings, perhaps indicative of underlying risk factors for the disorder. Several genes that were dysregulated in both individuals with schizophrenia and their siblings related to nucleosome and histone structure and function, suggesting a potential epigenetic mechanism underlying the risk state for the disorder. Nonpsychotic siblings also displayed some differences from comparison subjects that were not found in their affected siblings, suggesting that the dysregulation of some genes in peripheral blood may be indicative of underlying protective factors. This study, while exploratory, illustrated the potential utility and increased informativeness of including unaffected first-degree relatives in research in pursuit of peripheral biomarkers for schizophrenia. PMID- 21972138 TI - Metal-ion-promoted electron transfer between tetrathiafulvalene and quinone units within a calix[4]arene framework and tuning through coordination of the neighboring crown ether with a sodium cation. AB - A new calix[4]arene 1 with tetrathiafulvalene (TTF), quinone, and crown ether units in the lower rim was designed and synthesized with the aim to investigate the possibility to tune the metal-ion promoted electron transfer by coordination of the crown ether unit with additional metal ions. Both absorption and electron spin resonance (ESR) spectroscopic studies clearly indicate that electron transfer occurs efficiently from TTF to the quinone units in the presence of Sc(3+)/Pb(2+)/Zn(2+). Moreover, the intramolecular electron transfer within 1 induced by Zn(2+) can be switched off by addition of Na(+) and further turned on by addition of either Sc(3+) or Pb(2+). PMID- 21972137 TI - Preparation of hydrophilic polymer-grafted polystyrene beads for hydrophilic interaction chromatography via surface-initiated atom transfer radical polymerization. AB - A one-step procedure based on surface-initiated atom transfer radical polymerization (SI-ATRP) to hydrophilize monodisperse poly(chloromethylstyrene-co divinylbenzene) beads has been presented in this work, using 2-hydroxyl-3-[4 (hydroxymethyl)-1H-1,2,3-triazol-1-yl]propyl 2-methylacrylate (HTMA) as a monomer. The chain length of the grafted poly(HTMA) was controlled via varying the ratio of HTMA to initiator on the surface of the beads. When using the grafted beads as a stationary phase in hydrophilic interaction chromatography (HILIC), good resolution for nucleobases/nucleosides was obtained with acetonitrile aqueous solution as an eluent; while for phenolic acids and glycosides, they could be eluted and separated in the presence of TFA. The retention time of the solutes increased with the amount of the grafted HTMA. The retention mechanisms of solutes were investigated by the effects of mobile phase composition and buffer pH on the retention of solutes. The results illustrated that the retention behaviors of the tested solutes were dominated by hydrogen bonding interaction and electrostatic interaction. From the chemical structure of the ligands, the modified beads could not only be used as a stationary phase in HILIC, but also act as a useful building block to develop new stationary phases for other chromatographic modes such as affinity media. PMID- 21972139 TI - Phosphorus limitation for the colony formation, growth and photosynthesis of an edible cyanobacterium, Nostoc sphaeroides. AB - The percentage of spherical colonies from the trichomes of Nostoc sphaeroides reached 62-73% after 16 days with 50 and 250 MUM P, but only 10-15% at 0.5 and 5 MUM P. During colony formation from microcolonies to macrocolonies, the growth rates were 95, 206 and 244% higher, respectively at 5, 50 and 250 MUM P than that at 0.5 MUM P. The light-saturated photosynthetic rate, maximum electron transport rate and light-limited photosynthetic efficiency at 0.5 MUM P decreased, respectively, by 45, 51 and 32% than those at 250 MUM P. These indicated that the colony development, growth and photosynthetic capacities were restricted at low P level, suggesting that P might be an important factor limiting the productivity and distribution of N. sphaeroides in the field. PMID- 21972140 TI - Genome shuffling improves production of the low-temperature alkalophilic lipase by Acinetobacter johnsonii. AB - The production of a low-temperature alkalophilic lipase from Acinetobacter johnsonii was improved using genome shuffling. The starting populations, obtained by UV irradiation and diethyl sulfate mutagenesis, were subjected to recursive protoplast fusion. The optimal conditions for protoplast formation and regeneration were 0.15 mg lysozyme/ml for 45 min at 37 degrees C. The protoplasts were inactivated under UV for 20 min or heated at 60 degrees C for 60 min and a fusant probability of ~98% was observed. The positive colonies were created by fusing the inactivated protoplasts. After two rounds of genome shuffling, one strain, F22, with a lipase activity of 7 U/ml was obtained. PMID- 21972141 TI - Regulation of spheroid formation and function by microenvironmental geometric configuration. AB - The effects of microenvironmental geometric configurations on hepatocyte self assembly were investigated for the first time. Primary hepatocytes were cultured on a flat surface and in differently shaped hollow lumens of two gel types: a native hydrogel (alginate) and a synthetic hydrogel (polyethylene glycol, PEG). The lumens were in the shapes of a cylinder, triangular prism and square column. The results of cell morphology and functionality revealed that a better culture environment for rapid spheroid formation was achieved in the hollow lumens of alginate gel than on the flat surface. Among the lumen configurations, the cylindrical one was the best. Additionally, differences between cell behaviors on a flat surface and in a hollow cylinder lumen were more evident in the PEG hydrogel. Hence, a microenvironment with the proper geometric morphology can benefit the aggregation of hepatocytes and facilitate spheroid formation. PMID- 21972142 TI - Resolution of 2-nitroalcohols by Burkholderia cepacia lipase-catalyzed enantioselective acylation. AB - Racemic 2-nitro-1-phenylethanol was resolved by via enantioselective transesterification catalyzed by Burkholderia cepacia lipase. The reaction afforded excellent E values (E > 200) and enantioselectivity (up to >99% enantiomeric excesses [ee]) of both remaining substrates and acetylated product. Moreover, the lipase displayed high enantioselectivity in the resolution of additional 2-nitroalcohols (E up to >200). This method provides an efficient alternative for obtaining enantiopure 2-nitroalcohols. PMID- 21972143 TI - Analysis of HDAC1-mediated regulation of Runx2-induced osteopontin gene expression in C3h10t1/2 cells. AB - Histone deacetylases (HDACs) deacetylate lysine residues of histone and non histone proteins and thereby regulate the cell-cycle, gene expression, and several other processes. We have analyzed the effects of HDAC1 on Runx2-mediated regulation of osteopontin (OPN) promoter activation and gene expression in mesenchymal progenitor C3h10t1/2 cells and show that co-expression of HDAC1 along with Runx2 results in down-regulation of Runx2-induced OPN mRNA expression during both the proliferation and differentiation stages of C3h10t1/2 cells. Luciferase assay results revealed that HDAC1 efficiently down-regulated Runx2-stimulated OPN promoter activity in a dose-dependent manner whereas TSA relieved the HDAC1 mediated repression and up-regulated the Runx2-induced OPN promoter activity and mRNA expression. In vivo HDAC1 co-localized and physically interacted with Runx2 and associated with the OPN promoter. Thus, HDAC1 not only plays a critical role in regulation of Runx2-stimulated expression of osteogenic genes, like OPN, but also regulate the proliferation and differentiation stages of mesenchymal progenitor cells, such as C3h10t1/2. PMID- 21972144 TI - Stromal cell derived factor-1alpha enhances bone formation based on in situ recruitment: a histologic and histometric study in rabbit calvaria. AB - Histological methods were used to assess whether in situ recruitment using stromal cell derived factor-1alpha (SDF-1alpha) enhances bone formation. Four defects were created in the calvarias of 16 rabbits and filled with: (1) a blood clot only (group C); (2) autogenous bone particles (AB, 0.2 ml) (group AB); (3) AB (0.1 ml) + bone marrow derived stromal stem cells (group ABC); or (4) AB (0.1 ml) + SDF-1alpha (group ABS). Bone formation was significantly greater in groups AB and ABC compared with group ABS after 2 weeks (P < 0.05). Bone formation was similar between groups AB, ABC, and ABS after 4 weeks (P > 0.05). SDF-1alpha is a promising candidate for in situ recruitment in bone regeneration. PMID- 21972145 TI - Cloning of an endoglycanase gene from Paenibacillus cookii and characterization of the recombinant enzyme. AB - An endoglycanase gene of Paenibacillus cookii SS-24 was cloned and sequenced. This Pgl8A gene had an open reading frame of 1,230 bp that encoded a putative signal sequence (31 amino acids) and mature enzyme (378 amino acids: 41,835 Da). The enzyme was most homologous to a beta-1,3-1,4-glucanase of Bacillus circulans WL-12 with 84% identity. The recombinant enzyme hydrolyzed carboxymethyl cellulose, swollen celluloses, chitosan and lichenan but not Avicel, chitin powder or xylan. With chitosan as the substrate, the optimum temperature and hydrolysis products of the recombinant enzyme varied at pH 4.0 and 8.0. This is the first report that characterizes chitosanase activity under different pH conditions. PMID- 21972146 TI - Enhancing plant disease suppression by Burkholderia vietnamiensis through chromosomal integration of Bacillus subtilis chitinase gene chi113. AB - Burkholderia vietnamiensis P418 is a plant growth-promoting rhizobacteria. A chitinase gene from Bacillus subtilis was cloned and stably integrated into the chromosome of using the transposon delivery vector, pUTkm1. Chitinase activity was detected in recombinant P418-37 but not in wild type P418. Recombinant P418 37 retained the in vitro growth rate, N(2)-fixation and phosphate and potassium solubilizing characteristics of the wild type. P418-37 significantly (P < 0.05) increased in vitro inhibition of the plant pathogenic fungi Rhizoctonia solani, Fusarium oxysporum f.sp. vasinfectum, Rhizoctonia cerealis, Bipolaris sorokiniana, Verticillium dahliae and Gaeumannomyces graminis var. tritici compared with P418. In planta disease suppression assays indicated that P418-37 significantly (P < 0.05) enhanced suppression of wheat sheath blight (R. cerealis), cotton Fusarium wilt (F. oxysporium f.sp. vasinfectum) and tomato gray mould (Botrytis cinerea), relative to the wild type. PMID- 21972147 TI - Inhibition of hepatitis C virus replication by single and dual small interfering RNA using an HCV-infected cell model. AB - Dual siRNA against different regions of gene in hepatitis C virus (HCV) synergistically inhibited replication of HCV RNA. An HCV-infected cell model was established, and HCV RNA and core protein were detected by RT-PCR and Western blot, respectively. Four HCV-specific siRNAs (siCore, siNS3, siNS4B, siNS5B) were designed and transfected into HCV-infected Huh7.5.1 cells. The antiviral efficacies of the siRNAs were compared using real time PCR and agarose gel electrophoresis. HCV replication in infected cells was inhibited by IFNalpha-2b in a dose-dependent manner. Synergistic inhibition effects were achieved with combination treatment of any two of the siRNAs (siCore, siNS3 and siNS5B) at low doses (0.1 and 10 nM), as compared to single siRNA treatment (P < 0.05). Furthermore, CCK-8 assay showed no toxicity of the siRNAs to Huh7.5.1 cells. These findings indicate a promising new therapeutic approach for treatment of HCV. PMID- 21972148 TI - Resuscitating wild-type p53 expression by disrupting ceramide glycosylation: a novel approach to target mutant p53 tumors. AB - Mutant p53 is frequently detected in cancers in which p53 has lost its ability in tumor suppression and gained function in promoting tumor progression. Restoration of p53 functions by replacement of wild-type p53 and inhibition of its degradation or increment of its transcriptional activity has been applied to the prevention and treatment of cancers. Recent evidence indicates that disrupting ceramide glycosylation can resuscitate wild-type p53 expression and p53-dependent apoptosis in mutant p53 tumors. A posttranscriptional process that can turn on wild-type p53 expression and abrogate mutant p53 may provide a new strategy to eradicate mutant p53 cancers. PMID- 21972149 TI - Male eating disorder patients with and without non-suicidal self-injury: a comparison of psychopathological and personality features. AB - In the present study, we investigated the prevalence and comorbidity of non suicidal self-injury (NSSI) in male eating disorder (ED) patients. In total, 130 male ED patients completed a list of 10 impulse-control problems (including NSSI), the Eating Disorder Inventory-2, the Symptom Checklist-90-Revised and the Temperament and Character Inventory. Overall, 21% of the male ED patients (n = 27) engaged in at least one type of NSSI, and we did not find significant differences between the ED subtypes. Self-injurious male ED patients showed significantly more severe ED symptoms and more affective, interpersonal and impulse-control problems than ED patients without NSSI. As previously described in female ED, our data confirm the affect regulation and impulse regulation functions of NSSI in male ED patients. PMID- 21972151 TI - JICE goes "social". AB - Social media is transforming health care. The Journal of Interventional Cardiac Electrophysiology (JICE) has launched its own social media presence and is now on Facebook. JICE will post each issue's table of contents, special articles, online first publications to allow real-time notifications to JICE's readers and fans of our Facebook page. We encourage you to take the plunge and connect to our Facebook page. PMID- 21972150 TI - Self-management strategies in overweight and obese Canadians with arthritis. AB - OBJECTIVE: To estimate the prevalence of overweight and obese Canadians with arthritis and to describe their use of arthritis self-management strategies, as well as explore the factors associated with not engaging in any self-management strategies. METHODS: Respondents to the 2009 Survey on Living with Chronic Diseases in Canada, a nationally representative sample of 4,565 Canadians age >=20 years reporting health professional-diagnosed arthritis (including more than 100 rheumatic diseases and conditions), were asked about the impact of their arthritis and how it was managed. Among the overweight (body mass index [BMI] 25 29.9 kg/m(2)) and obese (BMI >=30 kg/m(2)) individuals with arthritis (n = 2,869), the use of arthritis self-management strategies (i.e., exercise, weight control/loss, classes, and community-based programs) were analyzed. Log binomial regression analyses were used to examine factors associated with engaging in none versus any (>=1) of the 4 strategies. RESULTS: More than one-quarter (27.4%) of Canadians with arthritis were obese and an additional 39.9% were overweight. The overweight and obese individuals with arthritis were mostly female (59.5%), age >=45 years (89.7%), and reported postsecondary education (69.0%). While most reported engagement in at least 1 self-management strategy (84.9%), less than half (45.6%) engaged in both weight control/loss and exercise. Factors independently associated with not engaging in any self-management strategies included lower education, not taking medications for arthritis, and no clinical recommendations from a health professional. CONCLUSION: Fewer than half of the overweight and obese Canadians with arthritis engaged in both weight control/loss and exercise. The provision of targeted clinical recommendations (particularly low in individuals that did not engage in any self-management strategies) may help to facilitate participation. PMID- 21972152 TI - Mutation of alpha-tubulin genes in trifluralin-resistant water foxtail (Alopecurus aequalis). AB - BACKGROUND: Trifluralin-resistant biotypes of water foxtail (Alopecurus aequalis) have been identified in wheat fields from northern Kyushu, Japan. Water foxtail is a winter-annual grassy weed, causing substantial crop losses. This study reports on mutation in alpha-tubulin (TUA) genes from water foxtail, the site of action of trifluralin. RESULTS: Two trifluralin-sensitive (S) Chikugo and Ukiha biotypes and four trifluralin-resistant (R) Asakura-1, Asakura-2, Tamana and Tosu biotypes of water foxtail were used for herbicide resistance analysis. R biotypes showed 5.7-30.7-fold trifluralin resistance compared with the S biotypes. No differences in the uptake and translocation of (14)C-trifluralin were observed between Chikugo (S) biotype and Asakura-1 (R) biotype. Most of the (14)C detected in the plant material was in the root tissue, and no substantial increases were noted in shoot tissues. Comparative TUA sequence analysis revealed two independent single amino acid changes: change of Val into Phe at position 202 in TUA1 and change of Leu into Met at position 125 in TUA3 in Asakura-1 biotype. In the Tamana (R) biotype, two amino acid changes of Leu to Phe at position 136 and Val to Phe at position 202 were observed in the predicted amino acid sequence of TUA1, compared with Chikugo (S) biotype. CONCLUSION: The results provide preliminary molecular explanation for the resistance of water foxtail to trifluralin, a phenomenon that has arisen as a result of repeated exposure to this class of herbicide. This is the first report of alpha-tubulin mutation in water foxtail and for any Alopecurus species reported in the literature. PMID- 21972153 TI - Peritoneal carcinomatosis: imaging with 64-MDCT and 3T MRI with diffusion weighted imaging. AB - Peritoneal carcinomatosis is usually associated with a poor overall survival rate. Recently, introduction of more aggressive surgical treatment and intraperitoneal chemotherapy appears to significantly increase the overall survival rate for these patients. A detailed preoperative assessment of peritoneal carcinomatosis could be very challenging in the field of imaging, but a new aggressive surgical approach requires an accurate preoperative assessment of the disease. Cross-sectional imaging using CT and MRI with diffusion-weighted imaging (DWI) sequences is important for appropriate management of patients with peritoneal carcinomatosis. Appreciation of the spectrum of diagnostic patterns and pitfalls as well as different sites of involvement of peritoneal carcinomatosis using CT and DWI is crucial for appropriate surgical treatment. PMID- 21972154 TI - Emergent versus elective percutaneous stent implantation in the unprotected left main: long-term outcomes from a single-center registry. AB - BACKGROUND: Unprotected left main (ULM) coronary disease is considered by contemporary guidelines a class I indication for surgery. However, percutaneous coronary intervention (PCI) is often carried out in the ULM in either emergent or high-risk elective procedures. The aim of this study was to evaluate ULM-PCI as a feasible and safe procedure in the emergent setting, and to analyze outcomes in both scenarios. METHODS: Angiographic and clinical data were collected retrospectively for all patients who underwent emergent or elective PCI on ULM at our center from January 2006 to June 2009. All patients were followed up with a clinical visit or telephone interview. Main outcomes included major adverse cardiac events (MACE) and its individual components: cardiac death, myocardial infarction (MI) and target lesion revascularization. These were analyzed at the longest follow-up available. RESULTS: A total of 98 consecutive patients with significant LM disease were included. Fifty-seven of them were treated as a planned procedure (elective group) and 41 as an emergent procedure (emergent group). Procedural success was achieved in 100% of cases in the elective group and in 88% of the emergent group (p = 0.011). Higher use of drug-eluting stents (DES) was recorded in the elective group (75% versus 45% in the emergent group; p <0.002). The emergent group presented a higher in-hospital mortality (24% versus 2% in the elective group; p <0.001). At a mean follow-up of 626 +/- 380 days, the overall MACE rate was similar betweeen the two groups (23% in the emergent group versus 17% in the elective group; p = 0.52). Independent predictors of MACE after discharge follow-up were postprocedure minimal diameter and DES use. CONCLUSIONS: Emergent PCI of the ULM exhibits worse in-hospital outcomes as compared to elective procedures. However, after discharge, long-term outcomes remain comparably good between groups. PMID- 21972155 TI - Left main stenting and landmark analysis - drawing the line. PMID- 21972156 TI - Changes in radial artery volume assessed using intravascular ultrasound: a comparison of two vasodilator regimens in transradial coronary interventions. AB - OBJECTIVES: This study used intravascular ultrasound (IVUS) to evaluate radial artery volume changes after intraarterial administration of nitroglycerin and/or verapamil. BACKGROUND: Radial artery spasm, which is associated with radial artery size, is the main limitation of the transradial approach in percutaneous coronary interventions (PCI). METHODS: This prospective, randomized study compared the effect of two intra-arterial vasodilator regimens on radial artery volume: 0.2 mg of nitroglycerin plus 2.5 mg of verapamil (Group 1; n = 15) versus 2.5 mg of verapamil alone (Group 2; n = 15). Radial artery lumen volume was assessed using IVUS at two time points: at baseline (5 minutes after sheath insertion) and post-vasodilator (1 minute after drug administration). The luminal volume of the radial artery was computed using ECOC Random Fields (ECOC-RF), a technique used for automatic segmentation of luminal borders in longitudinal cut images from IVUS sequences. RESULTS: There was a significant increase in arterial lumen volume in both groups, with an increase from 451 +/- 177 mm3 to 508 +/- 192 mm3 (p = 0.001) in Group 1 and from 456 +/- 188 mm3 to 509 +/- 170 mm3 (p = 0.001) in Group 2. There were no significant differences between the groups in terms of absolute volume increase (58 mm3 versus 53 mm3, respectively; p = 0.65) or in relative volume increase (14% versus 20%, respectively; p = 0.69). CONCLUSIONS: Administration of nitroglycerin plus verapamil or verapamil alone to the radial artery resulted in similar increases in arterial lumen volume according to ECOC-RF IVUS measurements. PMID- 21972157 TI - Radial artery spasm: pick the right cocktail and relax. PMID- 21972158 TI - Single-center experience of catheter ablation for atrial fibrillation using multi electrode mapping and ablation catheters. AB - PURPOSE: Radiofrequency ablation (RFA) is an established therapy for the treatment of paroxysmal and persistent atrial fibrillation (AF). Many techniques have been reported to achieve RFA. We report a single-center experience of RFA using three multi-electrode catheters. METHODS: We collected data of the patients who had RFA for AF using custom-designed multi-electrode mapping and ablation catheters between May 2007 and November 2009 at this center. RESULTS: A total of 105 patients aged 56 +/- 9.6 years underwent RFA using three multi-electrode catheters. Eighty-seven patients were new and 18 patients had re-do AF ablation using the multi-electrode mapping and ablation catheters. In the new patients, the mean procedure duration was 141 +/- 38 minutes and fluoroscopy time was 38 +/ 4 minutes. The mean duration of follow-up was 15.8 +/- 6.4 months. Symptomatic improvement was achieved in 75 patients (86%), 48 patients (55%) remained in sinus rhythm (SR) after the first procedure, while 7 (8%) had multiple procedures and remained in SR without antiarrhythmic drugs (AAD). Fourteen patients (16%) required AAD following a single procedure and 1 patient (1.1%) after multiple procedures to remain in SR. Seven patients (8%) had reduced burden of symptoms. No improvement occurred in 12 patients (13.7%). In the 18 re-do patients, 15 (83.3%) had symptom improvement. Four patients (22.2%) remained in SR after a single procedure and 4 patients (22.2%) required multiple procedures to remain in SR without AAD. One patient (5.5%) remained in SR on AAD following a single procedure and 1 patient (5.5%) remained in SR on AAD following multiple procedures. Five patients (27%) had reduced burden of symptoms and 3 patients (16.6%) had no improvement. CONCLUSION: PVI using multi-electrode mapping and ablation catheters is an effective treatment of paroxysmal and persistent AF with a complication rate equivalent to published data. PMID- 21972159 TI - Catheter ablation of atrial fibrillation: do the newer tools help? PMID- 21972160 TI - High-risk percutaneous coronary intervention with the TandemHeart and Impella devices: a single-center experience. AB - BACKGROUND: Intra-aortic balloon pumps (IABPs) are indicated during high-risk percutaneous coronary intervention (HR-PCI) to reduce major procedural complications. The clinical utility of the newer Impella and TandemHeart devices is not clear. This study determined the baseline characteristics, hemodynamics, and outcomes of patients treated with prophylactic percutaneous left ventricular assist devices (PLVADs) during HR-PCI. METHODS: A retrospective analysis at a private, tertiary referral hospital was conducted of all cases involving prophylactic PLVAD during HR-PCI between January 1, 2008 and June 30, 2010. General practice in this institution involves a tiered approach to PLVAD whereby patients with the least, intermediate, and highest risk of left ventricular failure are treated with an IABP, Impella, or TandemHeart, respectively. RESULTS: Fifty cases were identified (5 IABP, 13 Impella, 32 TandemHeart). Mean ejection fraction was 31 +/- 17%. All devices (100%) were initiated successfully. Angiographic success was achieved in 96% (80% IABP, 100% Impella, 97% TandemHeart). Of the 38 patients not in cardiogenic shock, death occurred in 1 (2.6%), recurrent ischemia in 3 (8%), and stroke in 0%. Shortly after device removal, systolic blood pressure (mean increase, +5 +/- 22 mmHg) and ejection fraction (mean increase, +7.4 +/- 11%; p = 0.0006) increased in all 3 groups, suggesting a beneficial effect on the myocardium. CONCLUSIONS: In patients undergoing HR-PCI with Impella and TandemHeart support, angiographic success was high and major complication rates were low. A tiered approach where patients with the least, intermediate, and highest risk of left ventricular failure are treated with an IABP, Impella, or Tandem- Heart, respectively, theoretically maximizes appropriate hemodynamic support and minimizes complications. Further studies are warranted. PMID- 21972161 TI - What is high-risk PCI, and how do you safely perform it? PMID- 21972162 TI - The StentBoost imaging enhancement technique as guidance for optimal deployment of adjacent-sequential stents. AB - Implantation of two or more adjacent-sequential stents is frequently required during coronary interventions, especially when treating long lesions. We present two cases illustrating that plain fluoroscopic imaging may be misleading when used for guiding optimal deployment of adjacent-sequential stents, whereas implementation of the StentBoostTM (Philips Medical Systems) fluoroscopic technique, which greatly enhances stent visualization in such procedures, may improve the assessment of stent positioning, preventing overlap failure or excessive overlapping. PMID- 21972163 TI - Flexions of the popliteal artery: technical considerations of femoropopliteal stenting. AB - Popliteal artery morphology changes while undergoing knee motion. A main flexion (i.e., the 'hinge point') and other flexions (termed 'accessory flexions') were described as a result of popliteal artery adaptation to knee flexion. Knee dynamics challenge the outcome of popliteal artery endovascular procedures. Complications such us stent fractures were reported despite rapidly improving technology. Understanding popliteal artery dynamics allows us to develop an endovascular technique that facilitates the avoidance of the difficulties of one of the most mobile arteries in the body. Here we report two cases with a novel stent implantation technique in the popliteal artery. The method includes diagnostic angiography, lesion angioplasty, and stenting using both extended and flexed knee in lateral view. The pressure gradients were measured with knee in extension and flexion before and after each step. A successful outcome was achieved in both cases. This method allows us: 1) to identify the flexions of the popliteal artery and its relationship with the lesions; 2) to detect those obstructions not visible with an extended knee; 3) to understand that the hinge point and accessory flexions can develop undesired and unexpected artery obstruction after a stent implantation only observed in knee flexion; and 4) to identify the morphological changes caused in the popliteal artery and its subsequent solution. PMID- 21972164 TI - Achieving optimal arterial access for PCI. PMID- 21972165 TI - The changing paradigm of hemodynamic support device selection for high-risk percutaneous coronary interventions. PMID- 21972166 TI - Occlusion of a left internal mammary artery graft side branch during attempts to deliver an amplatzer vascular plug. AB - We present a case of angina in a patient with a left internal mammary artery graft that had a large side branch. Closure was attempted using an Amplatzer vascular plug but during attempts to position the device, the side-branch occluded, likely due to dissection, obviating the need for device deployment. PMID- 21972167 TI - A case of effective reduction in the amount of contrast medium using selective coronary angiography with a thrombus aspiration catheter. AB - A 78-year-old male presented with exertional chest pain and renal dysfunction. Diagnostic coronary angiogram revealed severe subtotal occlusion in intermediate left anterior descending artery. We conducted percutaneous coronary intervention (PCI) and selective angiography with a thrombus aspiration catheter from the proximal part of the lesion using a contrast volume of only 2.5 ml. After marking the optimal location by in- travascular ultrasonography, we inserted a stent. Selective coronary angiography revealed good expansion. We could complete PCI using a contrast volume of only 5 ml in total. This strategy might be effective in preventing contrast-induced nephropathy. PMID- 21972168 TI - Aortic regurgitation following transcatheter closure of aortopulmonary window. AB - Natural history of aortic regurgitation (AR) following transcatheter closure (TCC) of intracardiac or aortopulmonary shunt needs to be explored. AR can appear immediately or later after TCC and may increase or regress. We describe a previously unreported AR development following successful TCC of aortopulmonary window. PMID- 21972169 TI - Coronary embolus complicating peripartum cardiomyopathy. AB - Peripartum cardiomyopathy is a rare disorder in which heart failure occurs during the last month of pregnancy or within 5 months of delivery, in the absence of any other etiology or prior heart disease. We present the case of a 42-year-old woman with peripartum cardiomyopathy. She was admitted with an acute myocardial infarction. Multiple mobile ventricular thrombi were seen in the echocardiogram. Coronary angiogram showed consequential coronary embolus occluding the left anterior descending artery. A successful embolectomy was performed followed by coronary stenting. There have been only two reports in the medical literature of coronary embolic events in the setting of peripartum cardiomyopathy; however, to our knowledge, we believe our case is the first to describe coronary intervention as treatment for the event. PMID- 21972170 TI - A rare anomaly of the aortic arch: aberrant right subclavian artery associated with common carotid trunk. AB - With increasing use of transradial access (TRA) to perform coronary angiography, arterial anomalies of the upper extremity are more frequently encountered. We describe a patient with an aberrant right subclavian artery (RSCA) originating as the last major branch of the aortic arch, which eventually led to failure of the transradial approach. Subsequent arch aortography revealed an associated common carotid trunk. The combination of both anomalies is a rare finding and may be associated with a number of other arterial and/or mediastinal organ anomalies. PMID- 21972171 TI - Complicated transcatheter closure of postinfarction ventricular acute septal defect. AB - The ventricular septal rupture is an uncommon complication of myocardial infarction (MI) with a reported incidence of 0.2% in the thrombolytic era. The outcome remains extremely poor, and surgical defect closure still remains the only therapeutic option improving survival. There are single reports based on a small series of case reports about transcatheter closure of postinfarction ventricular septal defects (VSD) and experience is limited. We present a case of a 71-year-old man with a posteroinferior MI complicated by a ventricular septal rupture with 24 mm width. Due to the severity of the case, surgical approach was denied; we attempted transcatheter closure of the defect in a lifesaving situation. The VSD was partially closed with a 26 mm Amplatzer(r) septal occluder (AGA Medical Corp., Plymouth, Minnesota) without adequate expansion of the right disc, due the complexity of the tract. The patient died one day after the procedure. PMID- 21972172 TI - Large perfusion defect on scintigraphy explained by severe microcirculatory dysfunction. PMID- 21972173 TI - Estimating non-Gaussian diffusion model parameters in the presence of physiological noise and Rician signal bias. AB - PURPOSE: To assess the effects of Rician bias and physiological noise on parameter estimation for non-Gaussian diffusion models. MATERIALS AND METHODS: At high b-values, there are deviations from monoexponential signal decay known as non-Gaussian diffusion. Magnitude images have a Rician distribution, which introduces a bias that appears as non-Gaussian diffusion. A second factor that complicates parameter estimation is physiological noise. It has an intensity that depends on the b-value in a complicated manner. Hence, the signal distribution is unknown a priori. By measuring a large number of averages, however, the variance at each b-value can be estimated. Using Monte Carlo simulations, we compared uncorrected estimation to a corrected scheme that involves fitting to the mean value of the Rician distribution. We also evaluated effects of weighting with the inverse of the estimated variance in least-squares fitting. A human brain experiment illustrates parameter estimation effects and identifies brain regions affected by physiological noise. RESULTS: The simulations show that the corrected estimator is very accurate. The uncorrected estimator is heavily biased. In the human brain experiment, the magnitude of the relative bias ranges from 6%-31%, depending on the diffusion model. Weighting has negligible effects on accuracy, but improves precision in the presence of physiological noise. At low b-values, physiological noise is prominent in cerebrospinal fluid. At high b-values there is physiological noise in white matter structures near the ventricles. CONCLUSION: Bias correction is essential and weighting may be beneficial. Physiological noise has significant effects. PMID- 21972174 TI - Simultaneous determination of eight active components in Houttuynia cordata injection and its quality control in productive process. AB - A simple, reliable and effective gas chromatography coupled with flame ionization detection method was developed for the simultaneous determination of eight components (alpha-pinene, beta-pinene, myrcene, limonene, terpinen-4-ol, alpha terpineol, bornyl acetate and methyl-n-nonylketone) in Chinese medicine Houttuynia cordata and its injection. The chromatographic separation of all eight components, including undecylene as internal standard was performed on a DB-1 column (30 m*0.25 mm, 0.25 MUm). Excellent linear behaviors including herb and injection over the investigated concentration ranges were observed with the values of r(2) higher than 0.9990 for all analytes. Satisfactory intra-day and inter-day precisions were achieved with RSD less than 2% and the average recoveries for all analytes at three different concentrations obtained were in the range of 93.4-104.4%, with RSD ranging from 1.3 to 4.1%. The proposed method was successfully applied in the simultaneous determination of these active components in H. cordata and H. cordata injection (HCI), including the intermediate product of HCI in productive process, from different pharmaceutical factories and different production batches, indicating that the method in this paper was particularly suitable for the routine analysis of HCI and its quality control in productive process. PMID- 21972175 TI - Functional analysis of variant lysosomal acid glycosidases of Anderson-Fabry and Pompe disease in a human embryonic kidney epithelial cell line (HEK 293 T). AB - The functional significance of missense mutations in genes encoding acid glycosidases of lysosomal storage disorders (LSDs) is not always clear. Here we describe a method of investigating functional properties of variant enzymes in vitro using a human embryonic kidney epithelial cell line. Site-directed mutagenesis was performed on the parental plasmids containing cDNA encoding for alpha-galactosidase A (alpha-Gal A) and acid maltase (alpha-Glu) to prepare plasmids encoding relevant point mutations. Mutant plasmids were transfected into HEK 293 T cells, and transient over-expression of variant enzymes was measured after 3 days. We have illustrated the method by examining enzymatic activities of four unknown alpha-Gal A and one alpha-Glu variants identified in our patients with Anderson-Fabry disease and Pompe diseases respectively. Comparison with control variants known to be either pathogenic or non-pathogenic together with over-expression of wild-type enzyme allowed determination of the pathogenicity of the mutation. One leader sequence novel variant of alpha-Gal A (p.A15T) was shown not to significantly reduce enzyme activity, whereas three other novel alpha-Gal A variants (p.D93Y, p.L372P and p.T410I) were shown to be pathogenic as they resulted in significant reduction of enzyme activity. A novel alpha-Glu variant (p.L72R) was shown to be pathogenic as this significantly reduced enzyme activity. Certain acid glycosidase variants that have been described in association with late-onset LSDs and which are known to have variable residual plasma and leukocyte enzyme activity in patients appear to show intermediate to low enzyme activity (p.N215S and p.Q279E alpha-Gal A respectively) in the over expression system. PMID- 21972176 TI - Association analysis of ANK3 gene variants in nordic bipolar disorder and schizophrenia case-control samples. AB - Genetic variants in ankyrin 3 (ANK3) have recently been shown to be associated with bipolar disorder (BD). We genotyped three ANK3 SNPs previously found to be associated with BD (rs10994336, rs1938526, and rs9804190) in a Scandinavian BD case-control sample (N = 854/2,614). Due to evidence of genetic overlap between BD and schizophrenia (SZ), we also genotyped these three SNPs in a Scandinavian SZ case-control sample (N = 1,073/2,919). Combining our Scandinavian samples with an Icelandic sample (N = 435 BD cases, 651 SZ cases, and 11,491 healthy controls), we found rs10994336 and rs9804190 to be nominally significantly associated with BD in this combined Nordic BD sample (N = 1,289/14,105). Nominal P was 0.015/0.018 (fixed/random effect) for rs10994336 (Bonferroni corrected P = 0.044/0.053) and 0.023 for rs9804190 (Bonferroni corrected P = 0.069). None of the SNPs were significantly associated with SZ in the combined Nordic SZ case control sample (N = 1,724/14,410). These results further support that ANK3 is a susceptibility gene specific to BD and that more than one risk locus is involved. PMID- 21972177 TI - Fish out of water: terrestrial jumping by fully aquatic fishes. AB - Many teleosts that live at the water's edge will voluntarily strand themselves to evade predators or escape poor conditions-this behavior has been repeatedly observed in the field for killifishes (Cyprinodontiformes). Although most killifishes are considered fully aquatic and possess no obvious morphological specializations to facilitate terrestrial locomotion, individuals from several different species have been observed moving across land via a "tail flip" behavior that generates a terrestrial jump. Like aquatic fast starts, terrestrial jumps are produced by high-curvature lateral flexion of the body (stage one), followed by contralateral flexion of the posterior body (stage two). Here, terrestrial jumps and aquatic fast starts are quantified for two littoral teleosts: Gambusia affinis (a killifish, Cyprinodontiformes) and Danio rerio (a small carp, Cypriniformes) to determine if the tail flip is produced by other (non-killifish) teleosts and to test the null hypothesis that the tail flip is a fast start behavior, performed on land. Both Danio and Gambusia produce tail flip driven terrestrial jumps, which are kinematically distinct from aquatic escapes and characterized by (1) a prolonged stage one, during which the fish bends, lifting and rolling the center of mass over the caudal peduncle, and (2) a relatively brief stage two, wherein the caudal peduncle pushes against the substrate to launch the fish into the aerial phase. The ability of these fully aquatic fishes to employ the same structure to produce distinct kinematic patterns in disparate environments suggests that a new behavior has evolved to facilitate movement on land and that anatomical novelty is not a prerequisite for effective terrestrial locomotion. PMID- 21972178 TI - Frequent discordance between clinical and musculoskeletal ultrasound examinations of foot disease in juvenile idiopathic arthritis. AB - OBJECTIVE: To evaluate the levels of agreement from independent clinical examination (CE) by a pediatric rheumatologist and podiatrist and an ultrasound (US) examination of articular and periarticular foot disease in juvenile idiopathic arthritis (JIA). METHODS: Thirty patients with JIA and a history of foot disease underwent CE and US examination of 24 foot joints, 10 tendons, and 6 periarticular soft tissues. Each site was examined independently by a rheumatologist and a podiatrist for synovitis and tenderness/swelling. The same sites were examined independently by a sonographer for effusion, synovial hypertrophy, power Doppler (PD) signal, tenosynovitis, or abnormal tendon thickening. Agreement was estimated using Cohen's unweighted kappa with corresponding 95% confidence intervals. RESULTS: Seven hundred twenty joints, 300 tendons, and 180 soft tissue sites were examined. Clinically detected synovitis, tenderness, and swelling were recorded in 42 (5.8%), 78 (10.8%), and 73 joints (10.1%), respectively. US-detected effusions, synovial hypertrophy, and PD signal were recorded in 88 (12.2%), 47 (6.5%), and 12 joints (1.7%), respectively. Subclinical foot disease was found in 52 joints (7.2%), 5 tendons (1.6%), and 4 soft tissue sites (2.2%). Agreement was consistently less than moderate (kappa = <0.4) for each clinical and US interaction. CONCLUSION: This study uniquely demonstrated an interprofessional evaluation of foot disease in JIA. Interobserver agreement was less than acceptable for CE versus US, and subclinical foot disease is common in joints and periarticular soft tissues. US may be a useful tool to aid CE of the foot in JIA patients. PMID- 21972180 TI - Organotypic slice culture from human adult ventricular myocardium. AB - AIMS: Cardiovascular research requires complex and functionally intact experimental models. Due to major differences in the cellular and subcellular composition of the myocardium between species, the use of human heart tissue is highly desirable. To enhance the experimental use of the human myocardium, we established methods for the preparation of vital tissue slices from the adult ventricular myocardium as well as conditions for their long-term preservation in organotypic culture. METHODS AND RESULTS: Human ventricular heart samples were derived from surgical specimens excised during a therapeutic Morrow myectomy and cut into 300 MUm thick slices. Slices were either characterized in acute experiments or cultured at a liquid-air interface. Viability and functionality were proven by viability staining, enzyme activity tests, intracellular potential recordings, and force measurements. Precision-cut slices showed high viability throughout 28 days in culture and displayed typical cardiomyocyte action potential characteristics, which enabled pharmacological safety testing on the rapid component of the delayed rectifier potassium current (I(Kr)) and ATP dependent potassium channels throughout the whole culture period. Constant expression of major ion channels was confirmed by quantitative PCR. Acute slices developed excitation-dependent contractions with a clear preload dependency and a beta-adrenergic response. Contractility and myosin light chain expression decreased during the first days in culture but reached a steady state with reactivity upon beta-adrenergic stimulation being preserved. CONCLUSION: Organotypic heart slices represent a multicellular model of the human myocardium and a novel platform for studies ranging from the investigation of molecular interactions to tissue engineering. PMID- 21972179 TI - Will it hurt less if I believe I can control it? Influence of actual and perceived control on perceived pain intensity in healthy male individuals: a randomized controlled study. AB - We explored the effects of uncontrollability and subjective helplessness (SHL) on perceived pain intensity (PPI) in 64 healthy men randomly assigned to groups receiving controllable (C) or uncontrollable (UC) painful electric skin stimuli. SHL (d = 1.43), perceived unpleasantness (d = 1.03), and PPI (d = 0.58) were more pronounced in the UC group than in the C group. Multiple regression and bootstrap analyses for testing mediation showed a direct relationship between stressor uncontrollability and PPI (r = 0.28; P < .05), which disappeared when adjusted for the SHL increase (beta = 0.49, P < .001). SHL changes were associated with objective uncontrollability (r = 0.59, P < .001). PPI and unpleasantness were positively correlated (r = 0.37, P < .01). The study suggests that the effect of objective controllability on pain intensity ratings is mediated mainly by ratings of SHL. PMID- 21972182 TI - [Recent advances of diffusion tensor imaging]. PMID- 21972181 TI - Surface modification of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) copolymer films for promoting interaction with bladder urothelial cells. AB - Often bladder dysfunction and diseases lead to therapeutic interventions that require partial or complete replacement of damaged tissue. For this reason, the development of biomaterials to repair the bladder by promoting the adhesion and growth of urothelial cells is of interest. With this aim, a modified copolyester of biocompatible and biodegradable poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(HB-co-HV)] was used as scaffold for porcine urothelial cell culture. In addition to good biocompatibility, the surface of P(HB-co-HV) substrates was modified to provide both, higher hydrophilicity and a better interaction with urothelial cells. Chemical treatments with ethylenediamine (ED) and sodium hydroxide (NaOH) led to substrate surfaces with decreasing hydrophobicity and provided functional groups that enable the grafting of bioactive molecules, such as a laminin derived YIGSR sequence. Physico-chemical properties of modified substrates were studied and compared with those of the pristine P(HB-co-HV). Urothelial cell morphology on treated substrates was studied. The results showed that focal attachment and cell-related properties were improved for peptide grafted polymer compared with both, the unmodified and functionalized copolyester. PMID- 21972183 TI - [Treatment of spontaneous spinal epidural hematoma]. AB - OBJECTIVE: Spontaneous spinal epidural hematoma (SSEH) is rare. There was not enough information about diagnosis and treatment of SSEH, although they require emergency surgery and some surgeons may hesitate to use alternative treatments. We report our six cases SSEH and discuss treatment of SSEH from the literature. MATERIALS AND METHODS: We encountered six cases of SSEH. They were 4 female and 2 male cases and age ranged from 61 to 75 years (averaging 67.3 years). The SSEH were located in the cervical (n=3), cervicothoracic (n=3) regions. In 4 cases, there were hematomas at the right side of the spinal epidural space, and 2 cases were at the left side. RESULTS: All cases experienced severe neck or shoulder pain. In five cases, hemiparesis was noted. Cervical MRI showed that epidural hematoma had compressed the spinal cord posterolateraly. In all cases, cervical CT scans also revealed epidural hematoma, too. Five cases were operated on by removal of the hematoma with hemilaminectomy and one case was operated on with laminectomy because of severe paresis. The mean time since the start of the operation was 11 hours (ranging from 7 to 20 hours). Only one case who had only severe pain without paresis was treated conservatively. All except two patients completely recovered neurologically. The two cases continued to have sensory disturbance. CONCLUSIONS: We successfully treated 6 cases of SSEH. MRI is useful for diagnosis of SSEH, and CT scan can also diagnose it as in our cases. Cases with severe neurological deficit would be considered as needing surgical treatment at an appropriate time and the cases without neurological deficit should be kept under observation until surgery becomes necessary. PMID- 21972184 TI - [Depiction of the cranial nerves around the cavernous sinus by 3D reversed FISP with diffusion weighted imaging (3D PSIF-DWI)]. AB - To evaluate the anatomy of cranial nerves running in and around the cavernous sinus, we employed three-dimensional reversed fast imaging with steady-state precession (FISP) with diffusion weighted imaging (3D PSIF-DWI) on 3-T magnetic resonance (MR) system. After determining the proper parameters to obtain sufficient resolution of 3D PSIF-DWI, we collected imaging data of 20-side cavernous regions in 10 normal subjects. 3D PSIF-DWI provided high contrast between the cranial nerves and other soft tissues, fluid, and blood in all subjects. We also created volume-rendered images of 3D PSIF-DWI and anatomically evaluated the reliability of visualizing optic, oculomotor, trochlear, trigeminal, and abducens nerves on 3D PSIF-DWI. All 20 sets of cranial nerves were visualized and 12 trochlear nerves and 6 abducens nerves were partially identified. We also presented preliminary clinical experiences in two cases with pituitary adenomas. The anatomical relationship between the tumor and cranial nerves running in and around the cavernous sinus could be three-dimensionally comprehended by 3D PSIF-DWI and the volume-rendered images. In conclusion, 3D PSIF-DWI has great potential to provide high resolution "cranial nerve imaging", which visualizes the whole length of the cranial nerves including the parts in the blood flow as in the cavernous sinus region. PMID- 21972185 TI - [Hypertensive intracerebral hemorrhage in isolated islands in Nagasaki Prefecture: a remote teleradiology and helicopter transportation system]. AB - Hypertensive intracerebral hemorrhage (HICH) causes significant morbidity and mortality. The time required to transport the patients to a specialized hospital can influence the prognosis. In the isolated islands in Nagasaki prefecture, there is no medical institution which can offer emergent neurosurgical intervention. We reviewed the cases of HICH in this region from January 2006 to September 2010, who were transferred to Nagasaki Medical Center by a helicopter after consultation via teleradiology. Eighty four cases (23%) were transferred via helicopter to our institution from isolated islands. In three of them (4%), re-hemorrhage was demonstrated on computed tomography after helicopter transportation, and one of three had been administered an anti-coagulant agent. Only one case (1%) has deteriorated during helicopter transportation because of acute obstructive hydrocephalus. The outcome at discharge was as follows: modified Rankin Scale (mRS) I: 3 cases (4%), II: 5 cases (6%), III: 3 cases (4%), IV: 30 cases (36%), V: 31 cases (37%), VI: 12 cases (14%), 43 cases (51%) showed poor outcome (mRS V, VI). For medical management in isolated islands, a remote teleradiology system is indispensable to decide a strategy of treatment rapidly, and a helicopter transportation system is very useful in cases requiring emergent neurosurgical intervention, particular in cases of impending cerebral herniation or acute hydrocephalus. However, we may need to expand logistical supporting hospitals or secure other transportation facilities because many of the patients with poor outcome can not return to their home islands. PMID- 21972186 TI - [A case of primary T-cell central nervous system lymphoma (T-PCNSL) relevant to HTLV-I]. AB - Primary T-cell lymphoma of the central nervous system lymphoma (T-PCNSL) is an extremely rare tumor. A human T-cell lymphoma virus type I(HTLV-I) associated adult TCL often involves the CNS during its course but disease limited to the CNS is exceptional. We report a case of a 63-year-old male with a highly malignant TCL localized in the bilateral cerebral hemispheres. The patient was HTLV-I positive but no systemic disease was detected after various examinations. We discuss the clinico-pathological features of TCL in the CNS reported in the literature including our case and compare them with those of B-cell lymphomas. PMID- 21972187 TI - [A case of intraosseous lipoma in the frontal bone]. AB - A case of intraosseous lipoma in the frontal bone was reported. A 62-year-old woman had a hard tumor affecting the right frontal bone. The slowly growing tumor was first noticed when she was in her late teens. The completely excised right frontal lesion was composed of mature adipose tissue with abundant fibrous stroma. Intraosseous lipoma affecting the skull is extremely rare, with only 17 cases having been reported previously. Presurgical diagnosis of intraosseous lipoma of the skull is difficult because of its non-specific radiological features. Pathological study is indispensable for a correct diagnosis. PMID- 21972188 TI - [Lumbar canal stenosis with overactive bladder presenting urinary incontinence developed by walking: a case report]. AB - A 74-year-old male complained of lower back pain, paresthesia of the bilateral feet and urinary incontinence. Urinary incontinence manifested at rest and worsened with walking. He had a history of surgery for prostatic cancer. Lumbar magnetic resonance imaging (MRI) demonstrated lumbar canal stenosis at the L4/5 level. The investigations including a cystometrogram manifested an overactive bladder caused by lumbar canal stenosis. His clinical symptoms were unresponsive to conservative treatment and posterior decompression at the L4/5 level was performed surgically to treat lumbar canal stenosis. Postoperatively, his symptoms were relieved. Overactive bladder presenting urinary incontinence that deteriorates with walking due to lumbar canal stenosis is suspected of being caused by circulatory disturbance of the cauda equine or conus medullaris. Emergency treatment including surgery is required for urinary retention in patients with lumbar canal stenosis; however, some degree of urinary disturbance may persist even after prompt and adequate surgery. Overactive bladder such as the present case should be considered as a possible symptom of lumbar canal stenosis, and surgical treatment for lumbar canal stenosis may be considered in the 'overactive bladder' stage before urinary retention begins, if the patient does not respond to conservative treatment. PMID- 21972189 TI - [A case of metastatic choroid plexus tumor from cholangiocellular carcinoma]. AB - Metastatic intraventricular tumor located in the choroid plexus is very rare. Only a few cases have been reported in the past. According to past reports, these tumors originated from lung, colon, and so on, but not from the bile duct. This is the first case report of choroid plexus metastasis from cholangiocellular carcinoma. A 57-year-old woman who had a history of cholagiocellular carcinoma, demonstrated intraventricular tumor. Although sufficient examination was performed, the tumor was difficult to diagnose as being a metastatic tumor or a choroid plexus carcinoma. Because of this, we performed endoscopic biopsy of the intraventricular tumor. However intraoperative findings were not helpful in distinguishing metastatic tumor and choroid plexus carcinoma. Postoperatively, histological examination was performed. However it was still difficult to differentiate this rare tumor from choroid plexus carcinoma by only hematoxylin and eosin stain. For further examination, Ber EP-4 stain was performed. Ber EP-4 showed strongly positive which indicates metastatic tumor. This method led us to make an appropriate diagnosis of this extremely rare tumor. We considered that in order to diagnose this rare tumor, appropriate histopathological examination, including immunohistopathological examination should be performed. PMID- 21972190 TI - [A case of symptomatic pituitary metastases from renal cell carcinoma]. AB - Symptomatic metastases to the pituitary from renal cell carcinoma are rare. We present a case of pituitary metastases from renal cell carcinoma showing panhypopituitarism. A 50-year-old man who had renal cell carcinoma with distant metastases in skin, bone and lymph nodes was referred to our department. Clinically he showed severe cognitive function disorder. Endocrinological evaluation revealed central adrenal and gonadal insufficiencies. Brain magnetic resonance imaging demonstrated a hemorrhagic mass in left frontal lobe and a sellar mass with supra sellar cistern extension. After hormonal replacement and surgical removal of the frontal tumor, he immediately recovered from his cognitive function disorder. Subsequently, whole brain radiotherapy for metastatic pituitary tumor was performed. At present, he is being treated with molecular targeting drugs for other distant metastases and he presents no neurological deficit. Palliative therapy for CNS metastases from renal cell carcinoma may result in better quality of life for patients with advanced stage of renal cell carcinoma. PMID- 21972191 TI - [Congenital anomalies in the central nervous system (11) Non-syndromic craniosynostosis]. PMID- 21972192 TI - Using dispersive liquid-liquid microextraction and liquid chromatography for determination of guaifenesin enantiomers in human urine. AB - A simple, rapid, and efficient method, dispersive liquid-liquid microextraction (DLLME) coupled with high-performance liquid chromatography-fluorescence detector, has been developed for the determination of guaifenesin (GUA) enantiomers in human urine samples after an oral dose administration of its syrup formulation. Urine samples were collected during the time intervals 0-2, 2-4, and 4-6 h and concentration and ratio of two enantiomers was determined. The ratio of R-(-) to S-(+) enantiomer concentrations in urine showed an increase with time, with R/S ratios of 0.66 at 2 h and 2.23 at 6 h. For microextraction process, a mixture of extraction solvent (dichloromethane, 100 MUL) and dispersive solvent (THF, 1 mL) was rapidly injected into 5.0 mL diluted urine sample for the formation of cloudy solution and extraction of enantiomers into the fine droplets of CH(2)Cl(2). After optimization of HPLC enantioselective conditions, some important parameters, such as the kind and volume of extraction and dispersive solvents, extraction time, temperature, pH, and salt effect were optimized for dispersive liquid-liquid microextraction process. Under the optimum extraction condition, the method yields a linear calibration curve in the concentration range from 10 to 2000 ng/mL for target analytes. LOD was 3.00 ng/mL for both of the enantiomers. PMID- 21972193 TI - Defence against oxidative stress in two species of land snails (Helix pomatia and Helix aspersa) subjected to estivation. AB - During summer, land snails are exposed to estivation/arousal cycles that imposes oxidative stress, but they exhibit different patterns of antioxidant defence. To test the ability of two related species, Helix pomatia and Helix aspersa, to modulate their antioxidant defence mechanism during estivation/arousal cycles, we examined activities of catalase and glutathione-related enzymes and concentrations of glutathione and thiobarbituric acid reactive substances (TBARS; as products of lipid peroxidation). In both species, estivation evoked changes in activity of total and selenium-dependent glutathione peroxidase (GPx), but did not affect activity of catalase, glutathione reductase, and glutathione transferase, and had no effect on concentration of glutathione. Activity of catalase in estivating snails, instead of the expected increase, showed a tendency to diminish. Extremely low activities of catalase in the foot were usually associated with extremely high activities of both forms of GPx. In conclusion, maintenance of relatively high activities of the antioxidant enzymes and accumulation of glutathione, resulting in a low and stable concentration of TBARS, plays an important role in scavenging oxygen free radicals from the organism of both species. PMID- 21972195 TI - Use of a virtual classroom in training fourth-year medical students on care transitions. AB - BACKGROUND: Transferring complex patients between settings can be fraught with poor communication and adverse outcomes, yet few medical students nationwide are trained in specific skills to improve care transitions. OBJECTIVE: To give medical students the fund of knowledge and skills to develop and implement a safe discharge plan. DESIGN: A new care transitions curriculum imparted to all fourth year medical students from August 2009 to April 2010 during their internal medicine sub-internship. SETTING: Emory University School of Medicine. INTERVENTION: Activities included: 1) discussion of an online case highlighting care transitions issues; 2) preparation of a discharge summary based on online templates; and 3) a postdischarge phone call to one of their patients. MEASUREMENTS: We evaluated the curriculum using questionnaires measuring changes in pretest to posttest confidence in performing discharge tasks, attitudes toward the care transitions process, and performance on a knowledge quiz. We also assessed course satisfaction and the quality of students' discharge summaries and postdischarge call reports performed during the module. RESULTS: Students' confidence in their ability to perform discharge tasks improved from 16.5 to 20.8 on a 25-point scale (P < 0.001). Knowledge quiz scores improved from 68 to 82 out of 100 (P < 0.001); 90.1% (109/121) of discharge summaries and 90.1% (109/121) of postdischarge call reports met all quality criteria. CONCLUSIONS: This curriculum showed that students could acquire the needed skills to prepare quality discharge summaries and communicate well with patients at discharge, as well as improve their overall knowledge surrounding care transitions. PMID- 21972194 TI - Prevalence of systemic lupus erythematosus and systemic sclerosis in the First Nations population of Alberta, Canada. AB - OBJECTIVE: To estimate the population-based prevalence of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) in Alberta, Canada, stratified by First Nations status. METHODS: Physician billing claims and hospitalization data for the province of Alberta (1994-2007) were used to ascertain cases of SLE and SSc using 3 case definitions. A latent class Bayesian hierarchical regression model was employed to account for the imperfect sensitivity and specificity of billing and hospitalization data in case ascertainment. We accounted for demographic factors, estimating prevalence rates for the First Nations and non First Nations populations by sex, age group, and location of residence (urban/rural). RESULTS: Our model estimated the prevalence of SLE in Alberta to be 27.3 cases per 10,000 females (95% credible interval [95% CrI] 25.9-28.8) and 3.2 cases per 10,000 males (95% CrI 2.6-3.8). The overall prevalence of SSc in Alberta was 5.8 cases per 10,000 females (95% CrI 5.1-6.5) and 1.0 case per 10,000 males (95% CrI 0.7-1.4). First Nations females over 45 years of age had twice the prevalence of either SLE or SSc relative to non-First Nations females. There was also a trend toward higher overall SLE prevalence in urban dwellers, and higher overall SSc prevalence in rural residents. CONCLUSION: First Nations females older than 45 years of age have an increased prevalence of either SLE or SSc. This may reflect a true predominance of autoimmune rheumatic diseases in this demographic, or may indicate systematic differences in health care delivery. PMID- 21972196 TI - Pyridostigmine bromide protection against acetylcholinesterase inhibition by pesticides. AB - Pyridostigmine bromide (PB) has been used to protect soldiers from the toxic effects of soman, a chemical warfare agent. Recent research shows that pyridostigmine bromide protects a significant percentage of acetylcholinesterase in isolated human intercostal muscle. Findings presented here indicate that red blood cell acetylcholinesterase is similarly protected by pyridostigmine bromide from the action of diisopropyl fluorophosphate and several organophosphate pesticides including chlorpyrifos-oxon, diazinon-oxon, and paraoxon, but not malaoxon, using the bovine red blood cell as a subject. These findings suggest that pretreatment with PB may protect growers, farmworkers, first responders, and the public, in general, from the effects of selected pesticides. PMID- 21972197 TI - Separation strategies for untargeted metabolomics. AB - Metabolomics has rapidly become a profiling technique of choice for biomarker elucidation and molecular diagnostics in addition to studies focused on understanding disease pathogenesis. Key to the success of metabolomics in these areas has been the techniques to separate and analyze the chemically diverse group of compounds comprising the metabolome by using global and untargeted approaches. Untargeted metabolomic efforts have the goal of examining as many metabolites as possible simultaneously and most frequently use an LC/MS-based approach. Here, the importance of LC in an untargeted metabolomic workflow is outlined and separation strategies for optimization are reviewed within the context of these criteria. PMID- 21972198 TI - Diabetes mellitus risk in rheumatoid arthritis: reduced incidence with anti-tumor necrosis factor alpha therapy. AB - OBJECTIVE: To examine the association of tumor necrosis factor alpha (TNFalpha) inhibitor use and the risk of developing diabetes mellitus in a rheumatoid arthritis (RA) inception cohort. METHODS: Adults diagnosed with RA between January 1, 2001, and December 31, 2009, were identified (n = 1,881). Prevalent cases of diabetes mellitus (n = 294) were excluded. Information on sociodemographic data, medical history, body mass index (BMI), laboratory measures, and medications was collected from the electronic health record. Incident diabetes mellitus was defined using the 2010 American Diabetes Association criteria or physician-established diagnosis. Time-varying Cox proportional hazards regression models were used to adjust for age, sex, race, BMI, rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP), erythrocyte sedimentation rate (ESR), and use of nonsteroidal antiinflammatory drugs (NSAIDs), glucocorticoids, hydroxychloroquine, and methotrexate. RESULTS: A total of 1,587 incident RA patients without diabetes mellitus were included. The anti-TNFalpha users (n = 522) had a lower median age but greater baseline BMI; maximum ESR, RF, and anti-CCP positivity; and NSAID, glucocorticoid, or methotrexate use. The median followup time for the ever and never TNFalpha inhibitor users was 44.9 months (interquartile range [IQR] 23.7 73.0 months) and 37.1 months (IQR 16.3-65.1 months), respectively (P < 0.001). Of the 91 patients developing diabetes mellitus, 16 were ever and 75 were never TNFalpha inhibitor users, yielding incidence rates of 8.6 and 17.2 per 1,000 person-years (P = 0.048), respectively. Adjusting for covariates, the hazard ratio for incident diabetes mellitus in TNFalpha inhibitor users was 0.49 (95% confidence interval 0.24-0.99, P = 0.049) compared to the never users. CONCLUSION: In this inception RA cohort, anti-TNFalpha use was associated with a 51% reduction in risk of developing diabetes mellitus. PMID- 21972199 TI - Differential expression of estrogen receptors in two hippocampal regions during the estrous cycle of the rat. AB - In the hippocampus, estrogens increase dendritic arborization, long-term potentiation, neuroprotection, and participate in many functions related with learning, memory, and affective behaviors. The presence of both estrogen receptors alpha (ERalpha) and beta (ERbeta) isoforms has been described in the hippocampus where they play different physiological roles. The aim of this study was to investigate, by using both techniques immunohistochemistry and Western Blot, the expression pattern of ERalpha and ERbeta in the hippocampus of the rat along the estrous cycle. Western blot analysis was used to confirm the specificity of the antibodies used against ERalpha and ERbeta and its relative content in the hippocampus. Results from immunohistochemical studies indicate that ERbeta expression increased more than the ERalpha in CA1 and CA3 regions during all phases of the estrous cycle. ERbeta immunoreactivity was mainly located in the nucleus and predominantly expressed in CA1 during estrous and metestrus, and in CA3 during diestrus. ERalpha was more abundant during estrous in comparison to other phases of the cycle in CA1 region, while it was more abundant during metestrus in CA3. Interestingly, the immunolocalization of ERalpha subtype was both cytoplasmic and nuclear. The overall results indicate that there is a differential expression, cellular localization, and distribution of both ER subtypes in CA1 and CA3 regions, suggesting different roles for these two receptors in the hippocampus along the estrous cycle. PMID- 21972200 TI - Cost-related medication underuse: prevalence among hospitalized managed care patients. AB - BACKGROUND: The affordability of prescription medications continues to be a major public health issue in the United States. Estimates of cost-related medication underuse come largely from surveys of ambulatory patients. Hospitalized patients may be vulnerable to cost-related underuse and its consequences, but have been subject to little investigation. OBJECTIVE: To determine impact of medication costs in a cohort of hospitalized managed care beneficiaries. METHODS: We surveyed consecutive patients admitted to medical services at an academic medical center. Questions about cost-related underuse were based on validated measures; predictors were assessed with multivariable models. Participants were asked about strategies to improve medication affordability, and were contacted after discharge to determine if they had filled newly prescribed medications. RESULTS: One-hundred thirty (41%) of 316 potentially eligible patients participated; 93 (75%) of these completed postdischarge surveys. Thirty patients (23%) reported cost-related underuse in the year prior to admission. In adjusted analyses, patients of black race were 3.39 times (95% confidence interval [CI], 1.05 to 11.02) more likely to report cost-related underuse than non-Hispanic white patients. Virtually all respondents (n = 123; 95%) endorsed at least 1 strategy to make medications more affordable. Few (16%) patients, prescribed medications at discharge, knew how much they would pay at the pharmacy. Almost none had spoken to their inpatient (4%) or outpatient (2%) providers about the cost of newly prescribed drugs. CONCLUSIONS: Cost-related underuse is common among hospitalized patients. Individuals of black race appear to be particularly at risk. Strategies should be developed to address this issue around the time of hospital discharge. PMID- 21972201 TI - Antibacterial nanofiber materials activated by light. AB - Electrospun polymeric nanofiber materials doped with 5,10,15,20 tetraphenylporphyrin (TPP) photosensitizer were prepared from four different polymers and were characterized with microscopic methods, steady-state, and time resolved fluorescence and absorption spectroscopy. The polymers used included polyurethane LarithaneTM (PUR), polystyrene (PS), polycaprolactone (PCL), and polyamide 6 (PA6). The antibacterial activity of all nanofiber materials against E. coli was activated by visible light and it was dependent on oxygen permeability/diffusion coefficients and the diameter of the polymeric nanofibers. This activity is based on oxidation ability of singlet oxygen O2(1Delta(g)) that is generated upon irradiation. All tested nanofiber materials exhibited prolonged antibacterial properties, even in the dark after long-duration irradiation. The post-irradiation effect was explained by the photogeneration of H2O2, which provided the material with long-lasting antibacterial properties. PMID- 21972202 TI - Separation of monosaccharides by solid-phase extraction with ionic liquid modified microporous polymers. AB - Ionic liquid-modified porous polymers with large surface area and large amount of functional groups were developed and used in SPE to separate four monosaccharides. Adsorption isotherm showed that the sorbent with amino ionic liquid groups had the highest interaction with the target compounds. The mobile phase of acetonitrile/water 85:15 and 73:30 v/v can successfully separate the monosaccharides. The sorbent produced reproducible results and performed stably, demonstrating its potential applicability in the separation of extract from natural plant. PMID- 21972203 TI - Rarity of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies in statin users, including those with self-limited musculoskeletal side effects. AB - OBJECTIVE: Statins, among the most commonly prescribed medications, are associated with a wide range of musculoskeletal side effects. These include a progressive autoimmune myopathy with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibodies that requires immunosuppression. However, it remains unknown whether these antibodies are found in statin users with and without self-limited musculoskeletal side effects; this limits their diagnostic utility. The current work assessed the prevalence of anti-HMGCR antibodies in these groups of statin users. METHODS: We determined the prevalence of anti-HMGCR antibodies in 1,966 participants (including 763 current statin users) in a substudy of the community-based Atherosclerosis Risk in Communities (ARIC) Study and 98 French Canadian subjects with familial hypercholesterolemia, including 51 with documented statin intolerance. RESULTS: No participant in the ARIC substudy, including those with past or current statin exposure at the time of sample collection, had anti-HMGCR antibodies. Similarly, none of 51 patients with self limited statin intolerance or 47 statin-tolerant patients receiving maximal statin therapy were anti-HMGCR positive. CONCLUSION: The majority of patients with and without statin exposure, including those with self-limited statin intolerance, do not develop anti-HMGCR antibodies. Therefore, anti-HMGCR antibodies are highly specific for those with an autoimmune myopathy. PMID- 21972204 TI - Pediatric hospitalist systems versus traditional models of care: effect on quality and cost outcomes. AB - BACKGROUND: Pediatric hospitalist systems are increasing in popularity, but data regarding the effects of hospitalist systems on the quality of care has been sparse, in part because rigorous metrics for analysis have not yet been established. We conducted a literature review of studies comparing the performance of pediatric hospitalists and traditional attendings. OBJECTIVE: To determine the effect of pediatric hospitalists on quality and outcome metrics such as length of stay, cost, patient satisfaction, mortality, readmission rates, and use of evidence-based medicine during care. RESULTS: A Medline literature search identified 11 studies that met criteria for inclusion. Five previously reviewed studies reported lengths of stay between 6% and 14% shorter for hospitalists. Five of the new studies evaluated lengths of stay, with 1 showing significantly lower length of stay and cost for a faculty model, 1 showing lower length of stay for hospitalists for all conditions, 1 for certain conditions only, and 2 showing no statistical difference. Six studies reported on readmission rate, with 4 showing no difference, 1 showing decreased readmissions for hospitalists, and 1 showing decreased readmissions for a traditional faculty service. Hospitalists self-report higher use of evidence-based guidelines. Few differences in patient satisfaction were reported. Mortality on the pediatrics wards is rare, and no studies were adequately powered to evaluate mortality rate. CONCLUSION: Hospitalists can improve the quality and efficiency of inpatient care in the pediatric population, but the effect is not universal, and mechanisms underlying demonstrated improvements are poorly understood. We propose 4 components to improve quality and value in hospital medicine systems: investment in comparative effectiveness research involving delivery system interventions, development and implementation of pediatric quality measures, better understanding of improvement mechanisms for hospital medicine systems, and increased focus on quality and value delivered by hospital medicine groups and individuals. PMID- 21972205 TI - Protein conformation changes on block copolymer surfaces detected by antibody functionalized atomic force microscope tips. AB - Conformational changes of fibronectin (Fn) deposited on poly(methyl methacrylate) and poly(acrylic acid) block copolymers with identical chemical compositions were detected using an antibody-functionalized atomic force microscope (AFM) tip. Based on the antibody-protein adhesive force maps and phase imaging, it was found that the nanomorphology of the triblock copolymer is conducive to the exposure of the arginine-glycine-aspartic acid (RGD) groups in Fn. For the first time, X-ray photoelectron spectroscopy was used to elucidate surface chemical composition and confirm AFM results. The findings demonstrate that block copolymer nanomorphology can be used to regulate protein conformation and potentially cellular response. PMID- 21972206 TI - Enantioselective micro-2D-HPLC determination of aspartic acid in the pineal glands of rodents with various melatonin contents. AB - Enantioselective determination of aspartic acid (Asp) in the pineal gland of rodents with various melatonin contents was performed using a highly sensitive and selective two-dimensional HPLC system. After derivatization of the amino group with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), NBD-Asp was separated using a capillary monolithic ODS column in the first dimension. The fraction of NBD-Asp was automatically collected and transferred to the second dimension, and the D- and L-Asp were separated and determined using a narrowbore enantioselective column. Large amounts of D-Asp were observed in the pineal gland of the rats and specific strains of mice (C3H and CBA) possessing a high concentration of melatonin in their pineal gland. On the other hand, the amounts of D-Asp were small in the pineal gland of mice possessing a trace or no melatonin in their pineal gland (ddY, ICR, C57BL and BALB/c). In other tissues and physiological fluids, no significant strain-dependent changes of the D-Asp amounts were observed. These results indicate that large amounts of D-Asp are present only in the pineal gland containing large amounts of melatonin, and special care should be taken when selecting mouse strains for the investigation of D-Asp. PMID- 21972207 TI - Relationship between obesity and foot pain and its association with fat mass, fat distribution, and muscle mass. AB - OBJECTIVE: To examine the relationship between obesity, body composition, and foot pain as assessed by the Manchester Foot Pain and Disability Index (MFPDI). METHODS: Subjects 25-62 years of age (n = 136) were recruited as part of a study examining the relationship between obesity and musculoskeletal health. Foot pain was defined as current foot pain and pain in the last month, and an MFPDI score of >=1. Body composition (tissue mass and fat distribution) was measured using dual x-ray absorptiometry. RESULTS: The body mass index (BMI) in this population was normally distributed around a mean of 32.1 kg/m(2). The prevalence of foot pain was 55.1%. There was a positive association between BMI and foot pain (odds ratio [OR] 1.11, 95% confidence interval [95% CI] 1.06-1.17). Foot pain was also positively associated with fat mass (OR 1.05, 95% CI 1.02-1.09) and fat mass index (FMI; OR 1.16, 95% CI 1.06-1.28) when adjusted for age, sex, and skeletal muscle mass and age, sex, and fat-free mass index (FFMI), respectively. When examining fat distribution, positive associations were observed for android/total body fat ratio (OR 1.42, 95% CI 1.11-1.83) and android/gynoid fat ratio (OR 35.15, 95% CI 2.60-475.47), although gynoid/total body fat ratio was inversely related to foot pain (OR 0.83, 95% CI 0.73-0.93). Skeletal muscle mass and FFMI were not associated with foot pain when adjusted for fat mass or FMI, respectively. CONCLUSION: Increasing BMI, specifically android fat mass, is strongly associated with foot pain and disability. This may imply both biomechanical and metabolic mechanisms. PMID- 21972208 TI - Severe adverse events associated with the use of second-line BCR/ABL tyrosine kinase inhibitors: preferential occurrence in patients with comorbidities. PMID- 21972209 TI - Epigenetics and mutations in chronic myeloproliferative neoplasms. PMID- 21972210 TI - Chronic lymphocytic leukemia--genomics lead the way. PMID- 21972211 TI - The levels of IL-17A and of the cytokines involved in Th17 cell commitment are increased in patients with chronic immune thrombocytopenia. AB - Th17 cells have been associated with immune-mediated diseases in humans but it has still not been determined whether they play a role in immune thrombocytopenia. We evaluated representative cytokines of the Th17, Th1, Th2 and Treg cell commitment in the serum of patients with chronic immune thrombocytopenia, as well as the cell source of IL-17A. Higher levels of IL-17A and Th17-related cytokines, and an increased percentage of IL-17A producing CD4+ and neutrophils were observed in patients. The levels of cytokines involved in Th1 cell commitment IFN-gamma, IL-2, IL12-p70 and the percentages of Th1 cells were also increased, but IL-4 was not detected. Although the concentrations of IL 10 were higher, the levels of TGF-beta were similar in both groups. In conclusion, our results point to a putative role for Th-17 cells/IL-17A cytokine in the pathogenesis of chronic immune thrombocytopenia. PMID- 21972212 TI - Evaluation of overall survival according to myelodysplastic syndrome-specific comorbidity index in a large series of myelodysplastic syndromes. PMID- 21972213 TI - Overexpression Nanog activates pluripotent genes in porcine fetal fibroblasts and nuclear transfer embryos. AB - Nanog as an important transcription factor plays a pivotal role in maintaining pluripotency and in reprogramming the epigenome of somatic cells. Its ability to function on committed somatic cells and embryos has been well defined in mouse and human, but rarely in pig. To better understand Nanog's function on reprogramming in porcine fetal fibroblast (PFF) and nuclear transfer (NT) embryo, we cloned porcine Nanog CDS and constructed pcDNA3.1 (+)/Nanog and pEGFP-C1/Nanog overexpression vectors and transfected them into PFFs. We studied the cell biological changes and the expression of Nanog, Oct4, Sox2, Klf4, C-myc, and Sall4 in transfected PFFs. We also detected the development potential of the cloned embryos harboring Nanog stably overexpressed fibroblasts and the expression of Oct4, Sox2, and both endogenous and exogenous Nanog in these embryos. The results showed that transient overexpression Nanog in PFF could activate the expression of Oct4 (5-fold), C-myc (2-fold), and Sall4 (5-fold) in somatic cells, but they could not be maintained during G418 selection. In NT embryos, although Nanog overexpression did not have a significant effect on blastocyst development rate and blastocyst cell number, it could significantly activate the expression of endogenous Nanog, Oct4, Sox2 to 160-fold, 93-fold, and 182-fold, respectively (P < 0.05). Our results demonstrate that Nanog could interact with and activate other pluripotent genes both in PFFs and embryos. PMID- 21972214 TI - Health insurance and length of stay for children hospitalized with community acquired pneumonia. AB - BACKGROUND: Disparities in patterns of care and outcomes for ambulatory-care sensitive childhood conditions such as community-acquired pneumonia (CAP) persist. However, the influence of insurance status on length of stay (LOS) for children hospitalized with CAP remains unexplored. METHODS: Secondary analysis of children (<18 years) hospitalized with CAP sampled in the Kids' Inpatient Database (KID) for years 1997, 2000, 2003, and 2006. Insurance status (private, public, uninsured) was based on claims data. Hospital LOS was calculated in days. Taking into account the complex sampling design, negative binomial regression models produced adjusted estimates of incidence rate ratios (IRR) for hospital LOS for children by insurance status. RESULTS: There was little variation in the categories of insurance status of children hospitalized with CAP between 1997 and 2006, with at least 40% privately insured, at least 40% publicly insured, and at least 5% uninsured in each sampled year. In all years, publicly insured children had a significantly longer hospital stay than privately insured children, and uninsured children had a significantly shorter hospital stay than privately insured children. These observed differences persisted after multivariate adjustment. CONCLUSIONS: Differences in LOS between uninsured, publicly insured, and privately insured children with CAP raise concerns about potential differences in hospital discharge practices related to insurance status and type. As healthcare reform is implemented, policy makers should strengthen efforts to reduce these disparities in order to achieve health for the population. PMID- 21972215 TI - Mediation of the migration of endothelial cells and fibroblasts on polyurethane nanocomposites by the activation of integrin-focal adhesion kinase signaling. AB - Model surfaces of polyurethane-gold nanocomposites (PU-Au) were used to examine cell behavior on nanophase-segregated materials. Previously we showed that endothelial cell (EC) migration on these materials was modulated by the PI3K/Akt/eNOS pathway. The present study, investigated the expressions of alpha5/beta3 (alpha5beta3) integrin, focal adhesion kinase (FAK), and other downstream signal molecules such as the Rho family and matrix metalloproteinases 2 (MMP-2) induced by the materials in two different cells, that is bovine arterial endothelial cells (BAEC) and human skin fibroblasts (HSF). Both cells proliferated better on the more phase-separated PU-Au 43.5 ppm than on the less phase-separated controls (PU and PU-Au 174 ppm). On PU-Au 43.5 ppm, BAEC compared to HSF had denser actin fibers and were more extended. BAEC became rounded with Y 27632 treatment and shrunk with LY294002 treatment. Treatment by inhibitors only caused slight changes in HSF. The migration distance of BAEC on PU-Au 43.5 ppm was greater than that of HSF, and was significantly reduced by LY294002 or Y 27632 but not SU-1498. The expressions of p-FAK, p-RhoA, p-Rac/Cdc42, MMP2, and alpha5beta3 integrin induced by PU-Au 43.5 ppm were more pronounced in BAEC versus HSF. Further enhancement in MMP2 and alpha5beta3 integrin expressions by FAK-GFP transfection was more remarkable for cells on PU-Au 43.5 ppm. Our findings suggested that the integrin alpha5beta3/FAK pathway may be induced by nanophase-separated materials in both ECs and fibroblasts to promote their proliferation/migration, while the crosstalk between the PI3K/Akt/eNOS pathway and FAK/Rho-GTPase activation may account for the greater effect in ECs than in fibroblasts. PMID- 21972216 TI - Magnetic solid-phase extraction using magnetic hypercrosslinked polymer for rapid determination of illegal drugs in urine. AB - A novel magnetic material Fe(3)O(4)/SiO(2)/P(MAA-co-VBC-co-DVB) was prepared via the hypercrosslinking of its precursor which was produced via precipitation polymerization of methacrylic acid (MAA), vinylbenzyl chloride (VBC), and divinylbenzene (DVB) in the presence of Fe(3)O(4)/SiO(2) submicrospheres with the surface containing abundant reactive double bonds. The resultant sorbent was characterized by scan electron microscopy, N(2) adsorption, and Fourier transform infrared spectroscopy. It was found that this material had remarkable features such as large surface area (500 m(2)/g) and pore volume (0.32 cm(3)/g), as well as desirable chemical composition (including hydrophobic and ion-exchange moieties). Taking advantages of the Fe(3)O(4)/SiO(2)/P(MAA-co-VBC-co-DVB), a magnetic SPE (MSPE) coupled with capillary electrophoresis (CE) method was developed for the determination of illegal drugs in urine samples. The extraction time could be clearly shortened up to 3 min. The recoveries of these drug compounds were in the range of 84.0-123% with relative standard deviations ranging between 1.7 and 10.5%; the limit of detection was in the range of 4.0-6.0 MUg/L. The proposed method is simple, effective, and low-cost, and provides an accurate and sensitive detection platform for abused drug analysis. PMID- 21972217 TI - Modified Phalen's test as an aid in diagnosing carpal tunnel syndrome. AB - OBJECTIVE: We developed a modified Phalen's test (MPT), which uses sensory testing in Phalen's position, as a diagnostic screening tool for carpal tunnel syndrome (CTS). This study was designed to determine the sensitivity, specificity, and receiver operating characteristic (ROC) curve of the MPT for diagnosis of CTS. METHODS: Electrodiagnostic nerve conduction studies (EDS) were used as the gold standard. MPT was performed by a blinded examiner on patients prior to EDS. MPT was recorded as either positive or negative based on the presence or absence of a median nerve sensory deficit while the hand was in Phalen's position. RESULTS: Sixty-six hands were included in this study. Chi square for the MPT compared to EDS as the gold standard was 41.449 (P < 0.001), and the validity coefficient (phi) was 0.792 (P < 0.01). The traditional Phalen's test (TPT) compared to the EDS demonstrated a chi-square of 15.349 (P < 0.001) and a phi coefficient of 0.482 (P < 0.01). ROC curve estimates for the MPT revealed a sensitivity of 84.4% compared to 50% for the TPT. The standard error of the estimate for sensitivity was 3.3% for the MPT and 5.8% for the TPT. CONCLUSION: The MPT is a highly useful screening diagnostic tool for CTS. The MPT demonstrates greater accuracy than the TPT for predicting CTS. The MPT also demonstrates greater sensitivity than the TPT in predicting a positive electrodiagnostic test for CTS. PMID- 21972218 TI - The dorsal sagittal venous sinus anatomical variations in brachycephalic, dolichocephalic, and mesocephalic dogs and their significance for brain surgery. AB - Dorsal sagittal venous sinus (DSVS) is an encephalic structure located in the midline of brain dorsal surface, starting behind the frontal venous sinus and following the brain falx in its extension. Knowing DSVS morphology and cranial cerebral relationships it is very important for surgeon when he is planning the placement of craniotomies, in order to prevent the damage of this structure. The main purpose of this study were to establish craniometric points that can be used as key points of neurosurgical importance providing an anatomic framework to brain access regarding the localization of DSVS, and to characterize the morphology of DSVS in the three groups considered in study according their type of skull (brachycephalic-B, dolychocephalic-D and mesocephalic-M). The study was performed on 138 formalin-fixed cerebral hemispheres of 69 adult dog cadavers (23 of each group) which had been removed from the skulls after the introduction of plastic catheters through properly positioned burr holes placed on the five craniometric points considered: asterion(ast), bregma(br), glabella(g), stephanion(st) and pterion(pt). From the three groups, DSVS length and width were different, his geometry in B assumed a triangular appearance and in D, M a "butterfly" shape. From all craniometric points considered, only bregma (br) can be useful as a landmark to delimitate DSVS morphology in all three groups. Asterion in M, stephanion in B, glabella and pterion in all three groups, can not be used to compose a framework that help to understand skull surface projection of DSVS morphology, since their measurements were not uniform. PMID- 21972219 TI - Optically and biologically active mussel protein-coated double-walled carbon nanotubes. AB - A method of dispersing strongly bundled double-walled carbon nanotubes (DWNTs) via a homogeneous coating of mussel protein in an aqueous solution is presented. Optical activity, mechanical strength, as well as electrical conductivity coming from the nanotubes and the versatile biological activity from the mussel protein make mussel-coated DWNTs promising as a multifunctional scaffold and for anti fouling materials. PMID- 21972220 TI - Chondrocyte redifferentiation in 3D: the effect of adhesion site density and substrate elasticity. AB - To obtain sufficient cell numbers for cartilage tissue engineering with autologous chondrocytes, cells are typically expanded in monolayer culture. As a result, they lose their chondrogenic phenotype in a process called dedifferentiation, which can be reversed upon transfer into a 3D environment. We hypothesize that the properties of this 3D environment, namely adhesion site density and substrate elasticity, would influence this redifferentiation process. To test this hypothesis, chondrocytes were expanded in monolayer and their phenotypical transition was monitored. Agarose hydrogels manipulated to give different RGD adhesion site densities and mechanical properties were produced, cells were incorporated into the gels to induce redifferentiation, and constructs were analyzed to determine cell number and extracellular matrix production after 2 weeks of 3D culture. The availability of adhesion sites within the gels inhibited cellular redifferentiation. Glycosaminoglycan production per cell was diminished by RGD in a dose-dependent manner and cells incorporated into gels with the highest RGD density, remained positive for collagen type I and produced the least collagen type II. Substrate stiffness, in contrast, did not influence cellular redifferentiation, but softer gels contained higher cell numbers and ECM amounts after 2 weeks of culture. Our results indicate that adhesion site density but not stiffness influences the redifferentiation process of chondrocytes in 3D. This knowledge might be used to optimize the redifferentiation process of chondrocytes and thus the formation of cartilage-like tissue. PMID- 21972221 TI - Decreased cytochrome c oxidase subunit VIIa in aged rat heart mitochondria: immunocytochemistry. AB - Aging decreases oxidative phosphorylation through cytochrome oxidase (COX) in cardiac interfibrillar mitochondria (IFM) in 24-month old (aged) rats compared to 6-month old adult Fischer 344 rats, whereas subsarcolemmal mitochondria (SSM) located beneath the plasma membrane remain unaffected. Immunoelectron microscopy (IEM) reveals in aged rats a 25% reduction in cardiac COX subunit VIIa in cardiac IFM, but not in SSM. In contrast, the content of subunit IV remains unchanged in both SSM and IFM, irrespective of age. These subunits are localized mainly on cristae membranes. In contrast, semi-quantitative immunoblotting, which detects denatured protein, indicates that the content of COX VIIa is similar in IFM and SSM from both aged and adult hearts. IEM provides a sensitive method for precise localizing and quantifying specific mitochondrial proteins. The lack of immunoreaction of COX VIIa subunit by IEM in aged IFM is not explained by a reduction in protein, but rather by a masking phenomenon or by an in situ change in protein structure affecting COX activity. PMID- 21972222 TI - Dipolar versus octupolar triphenylamine-based fluorescent organic nanoparticles as brilliant one- and two-photon emitters for (bio)imaging. AB - Two related triphenylamine-based dipolar and octupolar fluorophores are used to prepare aqueous suspensions of fluorescent organic nanoparticles (FONs) via the reprecipitation method. The obtained spherical nanoparticles (30-40 nm in diameter) are fluorescent in aqueous solution (up to 15% fluorescence quantum yield) and exhibit extremely high one- and two-photon brightness, superior to those obtained for quantum dots. Despite the two chromophores showing similar fluorescence in solution, the fluorescence of FONs made from the octupolar derivative is significantly red-shifted compared to that generated by the dipolar FONs. In addition, the maximum two-photon absorption cross section of the FONs made from the octupolar derivative is 55% larger than that of the dipolar derivative FONs. The experimental observations provide evidence that the different molecular shape (rodlike versus three-branched) and charge distribution (dipolar versus octupolar) of the two chromophores strongly affect the packing inside the nanoparticles as well as their spectroscopic properties and colloidal stability in pure water. The use of these FONs as probes for biphotonic in-vivo imaging is investigated on Xenopus laevis tadpoles to test their utilization for angiography. When using FONs made from the octupolar dye, the formation of microagglomerates (2-5 MUm scale) is observed in vivo, with subsequent lethal occlusion of the blood vessels. Conversely, the nanoparticles of the dipolar dye allow acute imaging of blood vessels thanks to their suitable size and brightness, while no toxic effect is observed. Such a goal cannot be achieved with the dissolved dye, which permeates the vessel walls. PMID- 21972223 TI - Peripheral nerve repair of transplanted undifferentiated adipose tissue-derived stem cells in a biodegradable reinforced nerve conduit. AB - This study proposes a biodegradable nerve conduit containing genipin-cross-linked gelatin annexed with tricalcium phosphate ceramic particles (genipin-gelatin tricalcium phosphate, GGT) in peripheral nerve regeneration. Firstly, cytotoxicity tests revealed that the GGT-extracts were not toxic, and promoted the proliferation and neuronal differentiation of adipose tissue-derived stem cells (ADSCs). Secondly, the GGT composite film effectively supported ADSCs attachment and growth. Additionally, the GGT substrate was biocompatible with the neonatal rat sciatic nerve and produced a beneficial effect on peripheral nerve repair through in vitro tissue culture. Finally, the experiments in this study confirmed the effectiveness of a GGT/ADSCs nerve conduit as a guidance channel for repairing a 10-mm gap in a rat sciatic nerve. Eight weeks after implantation, the mean recovery index of compound muscle action potentials (CMAPs) was significantly different between the GGT/ADSCs and autografts groups (p < 0.05), both of which were significantly superior to the GGT group (p < 0.05). Furthermore, walking track analysis also showed a significantly higher sciatic function index (SFI) score (p < 0.05) and better toe spreading development in the GGT/ADSCs group than in the autograft group. Histological observations and immunohistochemistry revealed that the morphology and distribution patterns of nerve fibers in the GGT/ADSCs nerve conduits were similar to those of the autografts. The GGT nerve conduit offers a better scaffold for the incorporation of seeding undifferentiated ADSCs, and opens a new avenue to replace autologous nerve grafts for the rapid regeneration of damaged peripheral nerve tissues and an improved approach to patient care. PMID- 21972224 TI - Cell response of Escherichia coli to cisplatin-induced stress. AB - Cisplatin is undoubtedly one of the most common and successful anticancer drugs worldwide. Though its DNA-based mechanism of action is well established, the contribution of the proteome to this process remains unclear. The possible impact of particular Escherichia coli proteins on the cytostatic activity of cisplatin was the subject of this study. Our main focus was not only the "bottom-up" identification of novel cisplatin protein targets through LC/LC-MS/MS analysis, but also a label-free quantification of their regulation profile by spectral counting. The regulation of two proteins, aconitate hydratase 2 and 60 kDa chaperonin 1, could be linked to a platinated amino acid in the protein sequence, whereas in the cases of 30S ribosomal protein S1 and enolase, it could be shown that cisplatin fragments are coordinated to an essential site for the functionality of the protein. Nucleoside triphosphate pyrophosphohydrolase (MazG) regulates the programmed cell death and was found to be platinated on the protein surface, which probably correlates with the established mode of action. A possible new chapter in the understanding of cisplatin's mechanism of action and its severe side effects is opened, since evidence is provided that platinated proteins are not only involved in cellular stress response but also in energy metabolism through glycolysis and catabolic processes, in gene regulatory mechanisms and protein synthesis. PMID- 21972226 TI - Development and validation of a prognostic nomogram for terminally ill cancer patients. AB - BACKGROUND: Determining life expectancy in terminally ill cancer patients is a difficult task. We aimed to develop and validate a nomogram to predict the length of survival in patients with terminal disease. METHODS: From February 1, 2003, to December 31, 2005, 406 consecutive terminally ill patients were entered into the study. We analyzed 38 features prognostic of life expectancy among terminally ill patients by multivariable Cox regression and identified the most accurate and parsimonious model by backward variable elimination according to the Akaike information criterion. Five clinical and laboratory variables were built into a nomogram to estimate the probability of patient survival at 15, 30, and 60 days. We validated and calibrated the nomogram with an external validation cohort of 474 patients who were treated from June 1, 2006, through December 31, 2007. RESULTS: The median overall survival was 29.1 days for the training set and 18.3 days for the validation set. Eastern Cooperative Oncology Group performance status, lactate dehydrogenase levels, lymphocyte levels, albumin levels, and time from initial diagnosis to diagnosis of terminal disease were retained in the multivariable Cox proportional hazards model as independent prognostic factors of survival and formed the basis of the nomogram. The nomogram had high predictive performance, with a bootstrapped corrected concordance index of 0.70, and it showed good calibration. External independent validation revealed 68% predictive accuracy. CONCLUSIONS: We developed a highly accurate tool that uses basic clinical and analytical information to predict the probability of survival at 15, 30, and 60 days in terminally ill cancer patients. This tool can help physicians making decisions on clinical care at the end of life. PMID- 21972225 TI - Pregnancy complications and obstetric suboptimality in association with autism spectrum disorders in children of the Nurses' Health Study II. AB - The authors examined pregnancy and obstetric complications in association with autism spectrum disorders (ASD) in children of participants from the Nurses' Health Study II, a prospective national cohort with information collected through biennial mailed questionnaires since 1989. Logistic regression was used to obtain crude and adjusted odds ratios for ASD, and by diagnostic subgroup. Seven hundred and ninety-three cases were reported among 66,445 pregnancies. Pregnancy complications and obstetric suboptimality factors were assessed by maternal report of occurrence in first birth and, in secondary analyses, in any birth. Complications and a suboptimality score were significantly associated with having a child with ASD (OR 1.49, 95% CI 1.26, 1.77, P<0.0001 for pregnancy complications in first birth and 2.76, 95% CI 2.04, 3.74, P<0.0001 comparing individuals with four or more obstetric suboptimality factors in first birth to those with none; results similar when assessed in any birth). In particular, gestational diabetes was associated with a significantly increased risk of ASD in results of primary and sensitivity analyses (OR in primary analysis = 1.76, 95% CI 1.34, 2.32, P<0.0001); suboptimal parity and suboptimal age-at-first-birth were also individual factors associated with ASD. Associations were similar by diagnostic subgroup, suggesting autism, Asperger syndrome, and other Pervasive Developmental Disorders are all associated with pregnancy complications. Consistent with previous research, the general class of pregnancy complications was associated with ASD as a whole. Additional work will be required to more fully assess the role of gestational diabetes. PMID- 21972227 TI - Antimalaria drug offers antitumor strategies. PMID- 21972228 TI - International Cancer Conference: targeted therapies boom expected in 3-5 years. PMID- 21972229 TI - StatBite. Number of MRI units per million population, 2010. PMID- 21972230 TI - Enthusiasm for antibody-drug conjugates. PMID- 21972231 TI - Cautious optimism for proposed European MRI exposure limit exemption. PMID- 21972232 TI - Molecular cloisonne: multicomponent organic alternating nanostructures at vicinal surfaces with tunable length scales. AB - By careful management of the adsorption preference of organic molecules at faceted vicinal surfaces, organic alternating structures can be extended to multilayers and multicomponent with tunable size scales ranging from several to a few tens nanometers. PMID- 21972233 TI - Accuracy of phenotyping children with autism based on parent report: what specifically do we gain phenotyping "rapidly"? AB - Autism spectrum disorder (ASD) is considered among the most heritable of all neurodevelopmental and psychiatric disorders, but identification of etiologically significant genetic markers and risk variants has been hampered by a lack of sufficiently large samples. Rapid phenotyping procedures, where self-report measures are used instead of extensive clinical assessment, have been proposed as methods for amassing large genetic databases due to their hypothesized time efficiency and affordability. We assessed the diagnostic accuracy of potential rapid phenotyping procedures using the Social Communication Questionnaire and the Social Responsiveness Scale in a sample of 333 children who also received extensive phenotypic assessments. While the rapid phenotyping measures were able to accurately identify a large number of children with ASD, they also frequently failed to differentiate children with ASD from children with other complex neurobehavioral profiles. These data support the continued need of expert clinical validation in combination with rapid phenotyping procedures in order to accurately amass large-scale genetic collections of children with ASD. PMID- 21972234 TI - Footwear characteristics and factors influencing footwear choice in patients with gout. AB - OBJECTIVE: Gout is associated with foot pain, impairment, and disability. The aim of this study was to assess footwear characteristics and key factors influencing footwear choice in patients with gout. We also wanted to evaluate the relationship between footwear characteristics and foot disability. METHODS: Fifty patients with a history of acute gout were recruited from rheumatology clinics during the summer months. Clinical characteristics, global function, and foot impairment and disability measures were recorded. Footwear characteristics and the factors associated with choice of footwear were identified using validated assessment tools. Suitability of footwear was assessed using predetermined criteria for assessing adequacy of footwear, based on a previous study of foot pain. RESULTS: The patients had moderate to severe foot pain, impairment, and disability. Poor footwear characteristics included poor cushioning, lack of support, lack of stability, and motion control. More than 50% of shoes were >=12 months old and demonstrated excessive wear patterns. Patients reported comfort (98%), fit (90%), support (90%), and cost (60%) as important factors in choosing their own footwear. No correlation was found between footwear characteristics (length and width) and foot characteristics (foot pain, impairment, and disability). Patients with poor footwear reported higher foot-related impairment and disability. CONCLUSION: Use of poor footwear is common in patients with chronic gout and is associated with foot disability and impairment. PMID- 21972236 TI - Pleiotropic opioid regulation of spinal endomorphin 2 release and its adaptations to opioid withdrawal are sexually dimorphic. AB - We studied adaptations to acute precipitated opioid withdrawal of spinal MU opioid receptor (MOR)-coupled regulation of the release of endomorphin 2 (EM2). The release of this highly MOR-selective endogenous opioid from opioid-naive spinal tissue of male rats is subjected to MOR-coupled positive as well as negative modulation via cholera toxin-sensitive G(s) and pertussis toxin sensitive G(i)/G(o), respectively. The net effect of this concomitant bidirectional modulation is inhibitory. MOR-coupled pleiotropic regulation of EM2 release is retained in opioid-withdrawn spinal tissue of male rats, but the balance of MOR-coupled inhibitory and facilitatory regulation shifted such that facilitatory regulation predominates. Augmented coupling of MOR to G(s) is causally associated with this change. Strikingly, pleiotropic characteristics of MOR-coupled regulation of spinal EM2 release and adaptations thereof to opioid withdrawal are male-specific. In females, MOR-coupled regulation of EM2 release from opioid-naive and -withdrawn spinal tissue does not have a significant G(s) coupled facilitatory component, and MOR-coupled inhibition of EM2 release persists unabated in withdrawn preparations. The male-specific adaptations to chronic morphine that shift the relative predominance of opposing dual G protein coupled MOR pathways provides a mechanism for mitigating inhibitory MOR signaling without losing MOR-coupled feedback regulation. These adaptations enable using endogenous EM2 as a substitute for morphine that had been precipitously removed. The sexually dimorphic functionality and regulation of spinal EM2/MOR-coupled signaling suggest the clinical utility of using sex-specific treatments for addiction that harness the activity of endogenous opioids. PMID- 21972237 TI - Analysis of R- and S-hydroxywarfarin glucuronidation catalyzed by human liver microsomes and recombinant UDP-glucuronosyltransferases. AB - Coumadin (R-, S-warfarin) is a challenging drug to accurately dose, both initially and for maintenance, because of its narrow therapeutic range and wide interpatient variability and is typically administered as a racemic (Rac) mixture, which complicates the biotransformation pathways. The goal of the current work was to identify the human UDP-glucuronosyltransferases (UGTs) involved in the glucuronidation of the separated R- and S-enantiomers of 6-, 7-, and 8-hydroxywarfarin and the possible interactions between these enantiomers. The kinetic and inhibition constants for human recombinant 1A family UGTs toward these separated enantiomers have been assessed using high-performance liquid chromatography (HPLC)-UV-visible analysis, and product confirmations have been made using HPLC-mass spectrometry/mass spectrometry. We found that separated R- and S-enantiomers of 6-, 7-, and 8-hydroxywarfarin demonstrate significantly different glucuronidation kinetics and can be mutually inhibitory. In some cases significant substrate inhibition was observed, as shown by K(m), V(max), and K(i), comparisons. In particular, UGT1A1 and extrahepatic UGT1A10 have significantly higher capacities than other isoforms for S-7-hydroxywarfarin and R 7-hydroxywarfarin glucuronidation, respectively. Activity data generated using a set of well characterized human liver microsomes supported the recombinant enzyme data, suggesting an important (although not exclusive) role for UGT1A1 in glucuronidation of the main warfarin metabolites, including Rac-6- and 7 hydroxywarfarin and their R- and S-enantiomers in the liver. This is the first demonstration that the R- and S-enantiomers of hydroxywarfarins are glucuronidated, with significantly different enzymatic affinity and capacity, and supports the importance of UGT1A1 as the major hepatic isoform involved. PMID- 21972238 TI - The transformation of enterovirus replication structures: a three-dimensional study of single- and double-membrane compartments. AB - All positive-strand RNA viruses induce membrane structures in their host cells which are thought to serve as suitable microenvironments for viral RNA synthesis. The structures induced by enteroviruses, which are members of the family Picornaviridae, have so far been described as either single- or double-membrane vesicles (DMVs). Aside from the number of delimiting membranes, their exact architecture has also remained elusive due to the limitations of conventional electron microscopy. In this study, we used electron tomography (ET) to solve the three-dimensional (3-D) ultrastructure of these compartments. At different time points postinfection, coxsackievirus B3-infected cells were high-pressure frozen and freeze-substituted for ET analysis. The tomograms showed that during the exponential phase of viral RNA synthesis, closed smooth single-membrane tubules constituted the predominant virus-induced membrane structure, with a minor proportion of DMVs that were either closed or connected to the cytosol in a vase like configuration. As infection progressed, the DMV number steadily increased, while the tubular single-membrane structures gradually disappeared. Late in infection, complex multilamellar structures, previously unreported, became apparent in the cytoplasm. Serial tomography disclosed that their basic unit is a DMV, which is enwrapped by one or multiple cisternae. ET also revealed striking intermediate structures that strongly support the conversion of single-membrane tubules into double-membrane and multilamellar structures by a process of membrane apposition, enwrapping, and fusion. Collectively, our work unravels the sequential appearance of distinct enterovirus-induced replication structures, elucidates their detailed 3-D architecture, and provides the basis for a model for their transformation during the course of infection. IMPORTANCE: Positive strand RNA viruses hijack specific intracellular membranes and remodel them into special structures that support viral RNA synthesis. The ultrastructural characterization of these "replication structures" is key to understanding their precise role. Here, we resolved the three-dimensional architecture of enterovirus induced membranous compartments and their transformation in time by applying electron tomography to cells infected with coxsackievirus B3 (CVB3). Our results show that closed single-membrane tubules are the predominant initial virus induced structure, whereas double-membrane vesicles (DMVs) become increasingly abundant at the expense of these tubules as infection progresses. Additionally, more complex multilamellar structures appear late in infection. Based on compelling intermediate structures in our tomograms, we propose a model for transformation from the tubules to DMVs and multilamellar structures via enwrapping events. Our work provides an in-depth analysis of the development of an unsuspected variety of distinct replication structures during the course of CVB3 infection. PMID- 21972239 TI - Raw sewage harbors diverse viral populations. AB - At this time, about 3,000 different viruses are recognized, but metagenomic studies suggest that these viruses are a small fraction of the viruses that exist in nature. We have explored viral diversity by deep sequencing nucleic acids obtained from virion populations enriched from raw sewage. We identified 234 known viruses, including 17 that infect humans. Plant, insect, and algal viruses as well as bacteriophages were also present. These viruses represented 26 taxonomic families and included viruses with single-stranded DNA (ssDNA), double stranded DNA (dsDNA), positive-sense ssRNA [ssRNA(+)], and dsRNA genomes. Novel viruses that could be placed in specific taxa represented 51 different families, making untreated wastewater the most diverse viral metagenome (genetic material recovered directly from environmental samples) examined thus far. However, the vast majority of sequence reads bore little or no sequence relation to known viruses and thus could not be placed into specific taxa. These results show that the vast majority of the viruses on Earth have not yet been characterized. Untreated wastewater provides a rich matrix for identifying novel viruses and for studying virus diversity. IMPORTANCE: At this time, virology is focused on the study of a relatively small number of viral species. Specific viruses are studied either because they are easily propagated in the laboratory or because they are associated with disease. The lack of knowledge of the size and characteristics of the viral universe and the diversity of viral genomes is a roadblock to understanding important issues, such as the origin of emerging pathogens and the extent of gene exchange among viruses. Untreated wastewater is an ideal system for assessing viral diversity because virion populations from large numbers of individuals are deposited and because raw sewage itself provides a rich environment for the growth of diverse host species and thus their viruses. These studies suggest that the viral universe is far more vast and diverse than previously suspected. PMID- 21972240 TI - Novel metabolic attributes of the genus cyanothece, comprising a group of unicellular nitrogen-fixing Cyanothece. AB - The genus Cyanothece comprises unicellular cyanobacteria that are morphologically diverse and ecologically versatile. Studies over the last decade have established members of this genus to be important components of the marine ecosystem, contributing significantly to the nitrogen and carbon cycle. System-level studies of Cyanothece sp. ATCC 51142, a prototypic member of this group, revealed many interesting metabolic attributes. To identify the metabolic traits that define this class of cyanobacteria, five additional Cyanothece strains were sequenced to completion. The presence of a large, contiguous nitrogenase gene cluster and the ability to carry out aerobic nitrogen fixation distinguish Cyanothece as a genus of unicellular, aerobic nitrogen-fixing cyanobacteria. Cyanothece cells can create an anoxic intracellular environment at night, allowing oxygen-sensitive processes to take place in these oxygenic organisms. Large carbohydrate reserves accumulate in the cells during the day, ensuring sufficient energy for the processes that require the anoxic phase of the cells. Our study indicates that this genus maintains a plastic genome, incorporating new metabolic capabilities while simultaneously retaining archaic metabolic traits, a unique combination which provides the flexibility to adapt to various ecological and environmental conditions. Rearrangement of the nitrogenase cluster in Cyanothece sp. strain 7425 and the concomitant loss of its aerobic nitrogen-fixing ability suggest that a similar mechanism might have been at play in cyanobacterial strains that eventually lost their nitrogen-fixing ability. IMPORTANCE: The unicellular cyanobacterial genus Cyanothece has significant roles in the nitrogen cycle in aquatic and terrestrial environments. Cyanothece sp. ATCC 51142 was extensively studied over the last decade and has emerged as an important model photosynthetic microbe for bioenergy production. To expand our understanding of the distinctive metabolic capabilities of this cyanobacterial group, we analyzed the genome sequences of five additional Cyanothece strains from different geographical habitats, exhibiting diverse morphological and physiological attributes. These strains exhibit high rates of N(2) fixation and H(2) production under aerobic conditions. They can generate copious amounts of carbohydrates that are stored in large starch-like granules and facilitate energy-intensive processes during the dark, anoxic phase of the cells. The genomes of some Cyanothece strains are quite unique in that there are linear elements in addition to a large circular chromosome. Our study provides novel insights into the metabolism of this class of unicellular nitrogen-fixing cyanobacteria. PMID- 21972241 TI - Early menopause is an independent predictor of rheumatoid arthritis. AB - BACKGROUND: As rheumatoid arthritis (RA) occurs more often in women than in men, it has been suggested that reproductive hormones may play an important role in the pathogenesis. METHODS: Between 1991 and 1996, 30 447 subjects (18 326 women) were included in a community-based health survey. Information on female hormonal changes and stress-related factors was obtained using a self-administered questionnaire. This population was linked to four different local and national RA registers. The medical records for patients with a diagnosis of RA were subjected to a structured review and all women with incident RA according to the 1987 American College of Rheumatology criteria after inclusion in the health survey were included in a nested case-control study. Matched controls (1:4) were selected from the health survey population. RESULTS: Early age at menopause (<=45 years) was associated with the subsequent development of RA (OR 2.42, 95% CI 1.32 to 4.45). The effect of early menopause remained significant after adjusting for smoking, level of education and length of breastfeeding (OR 1.92, 95% CI 1.02 to 3.64) CONCLUSION: RA was predicted by an early age at menopause. This implicates an influence of hormonal changes during the fertile period on the development of RA in postmenopausal women. PMID- 21972242 TI - Effectiveness of disease-modifying antirheumatic drug co-therapy with methotrexate and leflunomide in rituximab-treated rheumatoid arthritis patients: results of a 1-year follow-up study from the CERERRA collaboration. AB - OBJECTIVES: To compare the effectiveness and safety of rituximab alone or in combination with either methotrexate or leflunomide. METHODS: 10 European registries submitted anonymised datasets with baseline, 3, 6, 9 and 12-month clinical data from patients who started rituximab. RESULTS: 1195 patients were treated with rituximab plus methotrexate, 177 with rituximab plus leflunomide and 505 with rituximab alone. Significantly more patients achieved a European League Against Rheumatism good response at 6 months when treated with rituximab plus leflunomide (29.1%) compared with rituximab plus methotrexate (21.1%) and rituximab alone (19.3%; p=0.02 and p=0.01, respectively). Similar results were observed at 12 months. Adverse events occurred in 10.2%, 13.2% and 13.9% of patients on rituximab plus leflunomide, rituximab plus methotrexate and rituximab alone, respectively. CONCLUSIONS: Leflunomide is an effective and safe alternative to methotrexate as concomitant treatment with rituximab. Slightly better results were obtained by the combination of rituximab and leflunomide than rituximab and methotrexate, raising the possibility of a synergistic effect of leflunomide and rituximab. PMID- 21972243 TI - Hypoxia: a critical regulator of early human tendinopathy. AB - OBJECTIVES: To seek evidence for the role of hypoxia in early human tendinopathy, and thereafter to explore mechanisms whereby tissue hypoxia may regulate apoptosis, inflammatory mediator expression and matrix regulation in human tenocytes. METHODS: Fifteen torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing 'early pathology') biopsies were collected from patients undergoing arthroscopic shoulder surgery. Control samples of the subscapularis tendon were collected from 10 patients undergoing arthroscopic stabilisation surgery. Markers of hypoxia were quantified by immunohistochemical methods. Human tendon-derived primary cells were derived from hamstring tendon tissue obtained during hamstring tendon anterior cruciate ligament reconstruction. The impact of hypoxia upon tenocyte biology ex vivo was measured using quantitative real-time PCR, multiplex cytokine assays, apoptotic proteomic profiling, immunohistochemistry and annexin V fluorescence-activated cell sorter staining. RESULTS: Increased expression of hypoxia-inducible factor 1alpha, Bcl-2 and clusterin was detected in subscapularis tendon samples compared with both matched torn samples and non-matched control samples (p<0.01). Hypoxic tenocytes exhibited increased production of proinflammatory cytokines (p<0.001), altered matrix regulation (p<0.01) with increased production of collagen type III operating through a mitogen-activated protein kinase-dependent pathway. Finally, hypoxia increased the expression of several mediators of apoptosis and thereby promoted tenocyte apoptosis. CONCLUSION: Hypoxia promotes the expression of proinflammatory cytokines, key apoptotic mediators and drives matrix component synthesis towards a collagen type III profile by human tenocytes. The authors propose hypoxic cell injury as a critical pathophysiological mechanism in early tendinopathy offering novel therapeutic opportunities in the management of tendon disorders. PMID- 21972244 TI - Methylation of L1Hs promoters is lower on the inactive X, has a tendency of being higher on autosomes in smaller genomes and shows inter-individual variability at some loci. AB - LINE-1 repeats account for ~17% of the human genome. Little is known about their individual methylation patterns, because their repetitive, almost identical sequences make them difficult to be individually targeted. Here, we used bisulfite conversion to study methylation at individual LINE-1 repeats. The loci studied included 39 X-linked loci and 5 autosomal loci. On the X chromosome in women, we found statistically significant less methylation at almost all L1Hs compared with men. Methylation at L1P and L1M did not correlate with the inactivation status of the host DNA, while the majority of L1Hs that were possible to be studied lie in inactivated regions. To investigate whether the male-female differences at L1Hs on the X are linked to the inactivation process itself rather than to a mere influence of gender, we analyzed six of the L1Hs loci on the X chromosome in Turners and Klinefelters which have female and male phenotype, respectively, but with reversed number of X chromosomes. We could confirm that all samples with two X chromosomes are hypomethylated at the L1Hs loci. Therefore, the inactive X is hypomethylated at L1Hs; the latter could play an exclusive role in the X chromosome inactivation process. At autosomal L1Hs, methylation levels showed a correlation tendency between methylation level and genome size, with higher methylation observed at most loci in individuals with one X chromosome and the lowest in XXY individuals. In summary, loci-specific LINE-1 methylation levels show considerable plasticity and depend on genomic position and constitution. PMID- 21972245 TI - Transcriptional responses to loss or gain of function of the leucine-rich repeat kinase 2 (LRRK2) gene uncover biological processes modulated by LRRK2 activity. AB - Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are the most common genetic cause of Parkinson's disease (PD) and cause both autosomal dominant familial and sporadic PD. Currently, the physiological and pathogenic activities of LRRK2 are poorly understood. To decipher the biological functions of LRRK2, including the genes and pathways modulated by LRRK2 kinase activity in vivo, we assayed genome-wide mRNA expression in the brain and peripheral tissues from LRRK2 knockout (KO) and kinase hyperactive G2019S (G2019S) transgenic mice. Subtle but significant differences in mRNA expression were observed relative to wild-type (WT) controls in the cortex, striatum and kidney of KO animals, but only in the striatum in the G2019S model. In contrast, robust, consistent and highly significant differences were identified by the direct comparison of KO and G2019S profiles in the cortex, striatum, kidney and muscle, indicating opposite effects on mRNA expression by the two models relative to WT. Ribosomal and glycolytic biological functions were consistently and significantly up-regulated in LRRK2 G2019S compared with LRRK2 KO tissues. Genes involved in membrane-bound organelles, oxidative phosphorylation, mRNA processing and the endoplasmic reticulum were down-regulated in LRRK2 G2019S mice compared with KO. We confirmed the expression patterns of 35 LRRK2-regulated genes using quantitative reverse transcription polymerase chain reaction. These findings provide the first description of the transcriptional responses to genetically modified LRRK2 activity and provide preclinical target engagement and/or pharmacodynamic biomarker strategies for LRRK2 and may inform future therapeutic strategies for LRRK2-associated PD. PMID- 21972246 TI - Viable Staphylococcus aureus quantitation using 15N metabolically labeled bacteriophage amplification coupled with a multiple reaction monitoring proteomic workflow. AB - A multiple reaction monitoring liquid chromatography method with tandem mass spectrometric detection for quantitation of Staphylococcus aureus via phage amplification detection is described. This phage amplification detection method enables rapid and accurate quantitation of viable S. aureus by detecting an amplified capsid protein from a specific phage. A known amount of metabolically labeled (15)N reference bacteriophage, utilized as the input phage and as the internal standard for quantitation, was spiked into S. aureus samples. Following a 2-h incubation, the sample was subjected to a 3-min rapid trypsin digest and analyzed by high-throughput liquid chromatography tandem mass spectrometric detection targeting peptides unique to both the (15)N (input phage) and (14)N (progeny phage) capsid proteins. Quantitation was achieved by comparing peak areas of target peptides from the metabolically labeled (15)N bacteriophage peptide internal standard with that of the wild-type (14)N peptides that were produced by phage amplification and subsequent digestion when the host bacteria was present. This approach is based on the fact that a labeled species differs from the unlabeled one in terms of its mass but exhibits almost identical chemical properties such as ion yields and retention times. A 6-point calibration curve for S. aureus concentration was constructed with standards ranging from 5.0 * 10(4) colony forming units (CFU) ml(-1) to 2.0 * 10(6) CFU ml(-1), with the (15)N reference phage spiked at a concentration of 1.0 * 10(9) plaque forming units (PFU) ml(-1). Amplification with (15)N bacteriophage coupled with LC-MS/MS detection offers speed (3 h total analysis time), sensitivity (LOD: < 5.0 * 10(4) CFU ml(-1)), accuracy, and precision for quantitation of S. aureus. PMID- 21972248 TI - Rational design of novel anti-microtubule agent (9-azido-noscapine) from quantitative structure activity relationship (QSAR) evaluation of noscapinoids. AB - An anticough medicine, noscapine [(S)-3-((R)4-methoxy-6-methyl-5,6,7,8-tetrahydro [1,3]dioxolo[4,5-g]isoquinolin-5-yl)-6,7-dimethoxyiso-benzofuran-1(3H)-one], was discovered in the authors' laboratory as a novel type of tubulin-binding agent that mitigates polymerization dynamics of microtubule polymers without changing overall subunit-polymer equilibrium. To obtain systematic insight into the relationship between the structural framework of noscapine scaffold and its antitumor activity, the authors synthesized strategic derivatives (including two new ones in this article). The IC(50) values of these analogs vary from 1.2 to 56.0 uM in human acute lymphoblastic leukemia cells (CEM). Geometrical optimization was performed using semiempirical quantum chemical calculations at the 3-21G* level. Structures were in agreement with nuclear magnetic resonance analysis of molecular flexibility in solution and crystal structures. A genetic function approximation algorithm of variable selection was used to generate the quantitative structure activity relationship (QSAR) model. The robustness of the QSAR model (R(2) = 0.942) was analyzed by values of the internal cross-validated regression coefficient (R(2) (LOO) = 0.815) for the training set and determination coefficient (R(2) (test) = 0.817) for the test set. Validation was achieved by rational design of further novel and potent antitumor noscapinoid, 9 azido-noscapine, and reduced 9-azido-noscapine. The experimentally determined value of pIC(50) for both the compounds (5.585 M) turned out to be very close to predicted pIC(50) (5.731 and 5.710 M). PMID- 21972249 TI - Analytical and preparative instrumentation. PMID- 21972247 TI - Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) impairs the regulation of apoptosis in megakaryocytes by activating NF-kappaB: a proteomic study. AB - We previously showed that the Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and its receptor VPAC1 are negative regulators of megakaryopoiesis and platelet function, but their downstream signaling pathway that inhibits this process still remained unknown. A combined proteomic, transcriptomic, and bioinformatic approach was here used to elucidate the molecular mechanisms underlying PACAP signaling via VPAC1 in megakaryocytes. Two-dimensional difference gel electrophoresis and tandem MS were applied to detect differentially expressed proteins in megakaryocytic CHRF cells stimulated with PACAP. The majority of the 120 proteins modulated by PACAP belong to the class of "cell cycle and apoptosis" proteins. The up- or down-regulated expression of some proteins was confirmed by immunoblot and immunohistochemical analysis. A meta analysis of our data and 12 other published studies was performed to evaluate signaling pathways involved in different cellular models of PACAP response. From 2384 differentially expressed genes/proteins, 83 were modulated by PACAP in at least three independent studies and Ingenuity Pathway Analysis further identified apoptosis as the highest scored network with NF-kappaB as a key-player. PACAP inhibited serum depletion-induced apoptosis of CHRF cells via VPAC1 stimulation. In addition, PACAP switched on NF-kappaB dependent gene expression since higher nuclear levels of the active NF-kappaB p50/p65 heterodimer were found in CHRF cells treated with PACAP. Finally, a quantitative real time PCR apoptosis array was used to study RNA from in vitro differentiated megakaryocytes from a PACAP overexpressing patient, leading to the identification of 15 apoptotic genes with a 4-fold change in expression and Ingenuity Pathway Analysis again revealed NF kappaB as the central player. In conclusion, our findings suggest that PACAP interferes with the regulation of apoptosis in megakaryocytes, probably via stimulation of the NF-kappaB pathway. PMID- 21972250 TI - Testing relationships: ethical arguments for screening for type 2 diabetes mellitus with HbA1C. AB - Since the 1990s, glycated haemoglobin (HbA1C) has been the gold standard for monitoring glycaemic control in people diagnosed as having either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Discussions are underway about diagnosing diabetes mellitus on the basis of HbA1C titres and using HbA1C tests to screen for T2DM. These discussions have focused on the relative benefits for individual patients, with some attention directed towards reduced costs to healthcare systems and benefits to society. We argue that there are strong ethical reasons for adopting HbA1C-based diagnosis and T2DM screening that have not yet been articulated. The rationale includes the differential impact of HbA1C based diabetic testing on disadvantaged groups, and what we are beginning to learn about HbA1C vis-a-vis population health. Although it is arguable that screening must primarily benefit the individual, using HbA1C to diagnose and screen for T2DM may promote a more just distribution of health resources and lead to advances in investigating, monitoring and tackling the social determinants of health. PMID- 21972251 TI - Beers criteria as a proxy for inappropriate prescribing of other medications among older adults. AB - BACKGROUND: The Beers criteria are a compilation of medications deemed potentially inappropriate for older adults, widely used as a prescribing quality indicator. OBJECTIVE: To determine whether Beers criteria serve as a proxy measure for other forms of inappropriate prescribing, as measured by comprehensive implicit review. METHODS: Data for patients 65 years and older were obtained from the Veterans Affairs Enhanced Pharmacy Outpatient Clinic (EPOC) and the Iowa Medicaid Pharmaceutical Case Management (PCM) studies. Comprehensive measurement of prescribing quality was conducted using expert clinician review of medical records according to the Medication Appropriateness Index (MAI). MAI scores attributable to non-Beers medications were contrasted between patients who did and did not receive a Beers criteria medication. RESULTS: Beers criteria medications accounted for 12.9% (EPOC) and 14.0% (PCM) of total MAI scores. Importantly, non-Beers MAI scores were significantly higher in patients receiving a Beers criteria medication in both studies (EPOC: 15.1 vs 12.4, p = 0.02; PCM: 11.1 vs 8.7, p = 0.04), after adjusting for important confounding factors. CONCLUSIONS: Beers criteria utility extended beyond direct measurement of a limited set of inappropriate prescribing practices by serving as a clinically meaningful proxy for other inappropriate practices. Using prescribing quality indicators to guide interventions should thus identify patients for comprehensive medication review, rather than identifying specific medication targets for discontinuation. Future research should explore both the quality measurement and the intervention targeting applications of the Beers criteria, particularly when integrated with other indicators. PMID- 21972252 TI - Neuroleptic malignant syndrome associated with the use of prochlorperazine in a patient with a recent history of antipsychotic-induced neuroleptic malignant syndrome. AB - OBJECTIVE: To describe a case of neuroleptic malignant syndrome (NMS) associated with the use of prochlorperazine in a patient recently hospitalized for NMS secondary to olanzapine. CASE SUMMARY: A 28-year-old African American male with a history of schizophrenia was hospitalized 22 days prior to the current admission for an episode of olanzapine-induced NMS. The patient was discharged from our hospital to an outside psychiatric facility. At this facility, the patient developed nausea and was given 2 doses (unknown amount and route) of prochlorperazine. Over the next 24 hours, the patient exhibited signs and symptoms of NMS including fever, agitation, and muscle rigidity. He was transported to the emergency department and became increasingly agitated. Upon admission, the patient was hyperthermic (rectal temperature 39 degrees C) and tachycardic (heart rate 138 beats/min), with an elevated white blood cell count of 13.5 * 10(3)/MUL, creatine kinase 431 units/L, serum sodium 150 mEq/L, blood urea nitrogen 25 mg/dL, and creatinine 1.1 mg/dL. A diagnosis of NMS was speculated and infectious causes were excluded. The patient was treated with aggressive fluid resuscitation and rapid cooling measures, as well as bromocriptine and lorazepam. Cooling measures were used for 48 hours, during which time the creatine kinase, white blood cell count, sodium, blood urea nitrogen, and creatinine gradually normalized. The patient was discharged to a psychiatry facility with a treatment regimen of oxcarbazepine 600 mg twice daily, lorazepam 2 mg 3 times daily, and clozapine 25 mg at bedtime, which was titrated over 2 months to 200 mg twice daily. There have been no further occurrences of NMS. DISCUSSION: The patient had all of the major characteristics of NMS with no other likely causative factors that may have contributed to his illness. Use of the Naranjo probability scale suggested that NMS was probably related to prochlorperazine. This case highlights the potential increased risk with the use of prochlorperazine in a patient with a history of olanzapine-induced NMS. CONCLUSIONS: NMS should be considered as a rare complication of therapy with antipsychotics and agents that alter dopamine activity, especially in patients with a history of the syndrome. Careful consideration should be given regarding the risks and benefits of using non-antipsychotic dopamine antagonists in patients with a history of antipsychotic-induced NMS. PMID- 21972253 TI - Trophectoderm morphology: an important parameter for predicting live birth after single blastocyst transfer. AB - BACKGROUND: In order to select the best blastocyst for transfer, in humans, three morphological parameters have routinely been used, i.e. degree of blastocoele expansion and appearance of both the trophectoderm (TE) and the inner cell mass (ICM). Although it has been shown that blastocysts with highest scores for all three parameters achieve highest implantation rates, their independent ability to predict pregnancy outcome remains unclear. METHOD: This study is a retrospective analysis of 1117 fresh day 5 single blastocyst transfers and their live birth outcome related to each morphological parameter. RESULTS: All three parameters had a significant effect on live birth however, once adjusted for known significant confounders, it was shown that TE was the only statistically significant independent predictor of live birth outcome. CONCLUSIONS: This study has shown, for the first time, the predictive strength of TE grade over ICM for selecting the best blastocyst for embryo replacement. It may be that, even though ICM is important, a strong TE layer is essential at this stage of embryo development, allowing successful hatching and implantation. PMID- 21972254 TI - Developmental assessment of human vitrified-warmed blastocysts based on oxygen consumption. AB - BACKGROUND: In this study, we aimed to develop a model for embryo selection based on oxygen consumption following cryopreservation, the relationship between the developmental competence of blastocysts and their oxygen consumption was assessed. METHODS: Oxygen consumption of vitrified-warmed human blastocysts was measured at 0, 1.5, 3, 4.5, 6, 7.5, 9 and 24 h after warming using scanning electrochemical microscopy. On the basis of their developmental stage at 24 h, blastocysts were classified into four groups (hatched, hatching, arrested and degenerated). Moreover, cytochrome c oxidase (CCO) activity in vitrified-warmed blastocysts was assessed at 0 and 24 h. RESULTS: The oxygen consumption rate of blastocysts just after warming was significantly lower than that of non-vitrified blastocysts (P< 0.05). The oxygen consumption rate of blastocysts was significantly higher in the hatched group than in the arrested and the degenerated groups after 1.5 h (P< 0.05) and than in the hatching group (P< 0.05) at 7.5 and 9 h. Moreover, CCO activity was absent in vitrified-warmed blastocysts at 0 h, but was detected at 24 h. CONCLUSIONS: The respiratory rate of vitrified blastocysts after warming was significantly lower than non-cryopreserved blastocysts. Oxygen consumption of blastocysts with high developmental potential was restored earlier than that of blastocysts with low developmental potential. The results of this study suggest that it is possible to select vitrified-warmed blastocysts with high developmental potential based on their respiratory activity. PMID- 21972255 TI - Normal serum concentrations of anti-Mullerian hormone in a population of fertile women in their first trimester of pregnancy. AB - BACKGROUND: Anti-Mullerian hormone (AMH) levels are used to evaluate the ovarian reserve. AMH serum concentrations have recently been studied among women attending fertility centers, and among women with regular menstrual cycles but normative values have not been established among fertile women: the objective of this study was to establish those values. METHODS: This prospective cross sectional study included 340 healthy fertile women attending a single centre, aged between 15 and 50 years. The women were all in the first trimester of pregnancy, had no serious medical history and attended the abortion service of the University Hospital of Nice, France. Serum AMH was measured using a second generation AMH enzyme-linked immunosorbent assay. RESULTS: Median AMH concentration was 2.42 ng/ml (25-75 percentiles 1.19-4.12). The relationship between AMH concentration and age was best fitted by a polynomial function. Serum AMH values rose until age 29 years and then showed a significant decline (R(2)= 0.289, P < 0.001). Normative values for serum AMH were established in different age groups between 15 and 50 years. CONCLUSIONS: We established the normative values for serum AMH in a population of French fertile women in their first trimester of pregnancy. PMID- 21972256 TI - Molecular analyses of MADS-box genes trace back to Gymnosperms the invention of fleshy fruits. AB - Botanical fruits derive from ovaries and their most important function is to favor seed dispersal. Fleshy fruits do so by attracting frugivorous animals that disperse seeds together with their own excrements (endozoochory). Gymnosperms make seeds but have no ovaries to be transformed into fruits. Many species surround their seeds with fleshy structures and use endozoochory to disperse them. Such structures are functionally fruits and can derive from different anatomical parts. Ginkgo biloba and Taxus baccata fruit-like structures differ in their anatomical origin since the outer seed integument becomes fleshy in Ginkgo, whereas in Taxus, the fleshy aril is formed de novo. The ripening characteristics are different, with Ginkgo more rudimentary and Taxus more similar to angiosperm fruits. MADS-box genes are known to be necessary for the formation of flowers and fruits in Angiosperms but also for making both male and female reproductive structures in Gymnosperms. Here, a series of different MADS-box genes have been shown for the first time to be involved also in the formation of gymnosperm fruit like structures. Apparently, the same gene types have been recruited in phylogenetically distant species to make fleshy structures that also have different anatomical origins. This finding indicates that the main molecular networks operating in the development of fleshy fruits have independently appeared in distantly related Gymnosperm taxa. Hence, the appearance of the seed habit and the accompanying necessity of seed dispersal has led to the invention of the fruit habit that thus seems to have appeared independently of the presence of flowers. PMID- 21972257 TI - Triclosan antagonizes fluconazole activity against Candida albicans. AB - Triclosan is a broad-spectrum antimicrobial compound commonly used in oral hygiene products. Investigation of its activity against Candida albicans showed that triclosan was fungicidal at concentrations of 16 mg/L. However, at subinhibitory concentrations (0.5-2 mg/L), triclosan antagonized the activity of fluconazole. Although triclosan induced CDR1 expression in C. albicans, antagonism was still observed in cdr1Delta and cdr2Delta strains. Triclosan did not affect fluconazole uptake or alter total membrane sterol content, but did induce the expression of FAS1 and FAS2, indicating that its mode of action may involve inhibition of fatty acid synthesis, as it does in prokaryotes. However, FAS2 mutants did not exhibit increased susceptibility to triclosan, and overexpression of both FAS1 and FAS2 alleles did not alter triclosan susceptibility. Unexpectedly, the antagonistic effect was specific for C. albicans under hypha-inducing conditions and was absent in the non-filamentous efg1Delta strain. This antagonism may be due to the membranotropic activity of triclosan and the unique composition of hyphal membranes. PMID- 21972258 TI - Biologic mechanisms of oral cancer pain and implications for clinical therapy. AB - Cancer pain is an ever-present public health concern. With innovations in treatment, cancer patients are surviving longer, but uncontrollable pain creates a poor quality of life for these patients. Oral cancer is unique in that it causes intense pain at the primary site and significantly impairs speech, swallowing, and masticatory functions. We propose that oral cancer pain has underlying biologic mechanisms that are generated within the cancer microenvironment. A comprehensive understanding of key mediators that control cross-talk between the cancer and peripheral nervous system, and possible interventions, underlies effective cancer pain management. The purpose of this review is to explore the current studies on oral cancer pain and their implications in clinical management for cancer pain in general. Furthermore, we will explore the endogenous opioid systems and novel cancer pain therapeutics that target these systems, which could solve the issue of opiate tolerance and improve quality of life in oral cancer patients. PMID- 21972259 TI - A versatile monosaccharide transporter that operates in the arbuscular mycorrhizal fungus Glomus sp is crucial for the symbiotic relationship with plants. AB - For more than 400 million years, plants have maintained a mutualistic symbiosis with arbuscular mycorrhizal (AM) fungi. This evolutionary success can be traced to the role of these fungi in providing plants with mineral nutrients, particularly phosphate. In return, photosynthates are given to the fungus, which support its obligate biotrophic lifestyle. Although the mechanisms involved in phosphate transfer have been extensively studied, less is known about the reciprocal transfer of carbon. Here, we present the high-affinity Monosaccharide Transporter2 (MST2) from Glomus sp with a broad substrate spectrum that functions at several symbiotic root locations. Plant cell wall sugars can efficiently outcompete the Glc uptake capacity of MST2, suggesting they can serve as alternative carbon sources. MST2 expression closely correlates with that of the mycorrhiza-specific Phosphate Transporter4 (PT4). Furthermore, reduction of MST2 expression using host-induced gene silencing resulted in impaired mycorrhiza formation, malformed arbuscules, and reduced PT4 expression. These findings highlight the symbiotic role of MST2 and support the hypothesis that the exchange of carbon for phosphate is tightly linked. Unexpectedly, we found that the external mycelium of AM fungi is able to take up sugars in a proton-dependent manner. These results imply that the sugar uptake system operating in this symbiosis is more complex than previously anticipated. PMID- 21972260 TI - Tissue-autonomous promotion of palisade cell development by phototropin 2 in Arabidopsis. AB - Light is an important environmental information source that plants use to modify their growth and development. Palisade parenchyma cells in leaves develop cylindrical shapes in response to blue light; however, the photosensory mechanism for this response has not been elucidated. In this study, we analyzed the palisade cell response in phototropin-deficient mutants. First, we found that two different light-sensing mechanisms contributed to the response in different proportions depending on the light intensity. One response observed under lower intensities of blue light was mediated exclusively by a blue light photoreceptor, phototropin 2 (PHOT2). Another response was elicited under higher intensities of light in a phototropin-independent manner. To determine the tissue in which PHOT2 perceives the light stimulus to regulate the response, green fluorescent protein (GFP)-tagged PHOT2 (P2G) was expressed under the control of tissue-specific promoters in the phot1 phot2 mutant background. The results revealed that the expression of P2G in the mesophyll, but not in the epidermis, promoted palisade cell development. Furthermore, a constitutively active C-terminal kinase fragment of PHOT2 fused to GFP (P2CG) promoted the development of cylindrical palisade cells in the proper direction without the directional cue provided by light. Hence, in response to blue light, PHOT2 promotes the development of cylindrical palisade cells along a predetermined axis in a tissue-autonomous manner. PMID- 21972262 TI - Glaucoma research community and FDA look to the future, II: NEI/FDA Glaucoma Clinical Trial Design and Endpoints Symposium: measures of structural change and visual function. PMID- 21972263 TI - Adherence and preexisting major protease inhibitor resistance mutations are associated with virologic failure of a dual-class antiretroviral regimen with inhibitors of HIV-1 viral protease and integrase. AB - OBJECTIVES: Novel treatment strategies are needed for treatment-experienced HIV infected individuals. We retrospectively evaluated virologic outcomes on a dual class, protease inhibitor (PI) plus raltegravir, antiretroviral (ARV) regimen. METHODS: Virologic success was defined by a plasma HIV-RNA level <=200 copies/mL. Adherence was measured using pharmacy refill data. The association between adherence and virologic failure was assessed using bivariate logistic regression. RESULTS: In 39 individuals, median prior antiretroviral therapy (ART) exposure was 11 years. Of 39 individuals, 36 (92%) achieved an HIV-RNA <=200 copies/mL. After a median follow-up of 328 days (interquartile range [IQR] 190-737 days), 74% maintained an HIV-RNA <200 copies/mL but only 44% had <50 copies/mL. Median adherence was 96.4% (IQR 83.3%-100%). For every 10% decrease in adherence, the odds of virologic failure increased by 90% (odds ratio [OR] = 1.9, 95% confidence interval [CI] 1.1-3.3). In all, 4 individuals had >=2 preexisting major PI resistance mutations and all 4 had virologic failure. CONCLUSIONS: Most treatment experienced individuals achieved virologic suppression on a dual-class regimen of a PI plus raltegravir. Success was limited by poor medication adherence and preexisting major PI resistance mutations. PMID- 21972264 TI - Reverse transcriptase genotypes in pediatric patients failing initial antiretroviral therapy in Gaborone, Botswana. AB - BACKGROUND: Limited data are available on patterns of resistance mutations in pediatric patients in southern Africa, where HIV-1 subtype C (HIV-1C) predominates. METHODS: Retrospective chart review of pediatric patients. Nucleoside reverse transcriptase inhibitor (NRTI)- and nonnucleoside reverse transcriptase inhibitor (NNRTI)-associated resistance mutations quantified from population-based sequencing genotypic resistance assay results taken at time of first-line antiretroviral therapy (ART) failure (first-line ART = stavudine [d4T] or zidovudine [ZDV] + lamivudine [3TC] + nevirapine [NVP] or efavirenz [EFV]). RESULTS: Total number of patients with resistance assays analyzed is 45. Nucleoside reverse transcriptase inhibitor-associated mutation frequencies noted were M184V (n = 41; 91.1%); thymidine analogue mutations (TAMs; n = 20; 44.4%); >1 TAM (n = 9; 20%); TAM-2 pathway (n = 10; 22.2%); TAM-1 pathway (n = 7; 15.6%); TAM-1 and TAM-2 pathways (n = 3; 6.7%); K65R (n = 2; 4.4%); Q151M (n = 1; 2.2%); and L74V (n = 0; 0%). Nonnucleoside reverse transcriptase inhibitor-associated mutation frequencies noted were associated with notable resistance to either/both NVP and EFV (n = 40; 88.9%); K103N (n = 15; 33.3%); >=1 mutations associated with etravirine (ETR) failure (K101E, Y181C, and G190A; n =20; 44.4%); and >=2 notable NNRTI mutations (n = 12; 26.7%). CONCLUSIONS: In this cohort, low-genetic barrier mutations were common, as were TAMs, including more than 1 TAM. Mutations compromising nonthymidine analogue backbones were rare, suggesting that it is likely that children who fail first-line NRTI backbones containing d4T or ZDV/3TC would still respond to abacavir (ABC), didanosine (ddI), and, for adolescents, tenofovir (TDF). Our data support the empiric continuation of 3TC in second-line regimens. PMID- 21972261 TI - SCAR mediates light-induced root elongation in Arabidopsis through photoreceptors and proteasomes. AB - The ARP2/3 complex, a highly conserved nucleator of F-actin, and its activator, the SCAR complex, are essential for growth in plants and animals. In this article, we present a pathway through which roots of Arabidopsis thaliana directly perceive light to promote their elongation. The ARP2/3-SCAR complex and the maintenance of longitudinally aligned F-actin arrays are crucial components of this pathway. The involvement of the ARP2/3-SCAR complex in light-regulated root growth is supported by our finding that mutants of the SCAR complex subunit BRK1/HSPC300, or other individual subunits of the ARP2/3-SCAR complex, showed a dramatic inhibition of root elongation in the light, which mirrored reduced growth of wild-type roots in the dark. SCAR1 degradation in dark-grown wild-type roots by constitutive photomorphogenic 1 (COP1) E3 ligase and 26S proteasome accompanied the loss of longitudinal F-actin and reduced root growth. Light perceived by the root photoreceptors, cryptochrome and phytochrome, suppressed COP1-mediated SCAR1 degradation. Taken together, our data provide a biochemical explanation for light-induced promotion of root elongation by the ARP2/3-SCAR complex. PMID- 21972265 TI - Posttranslational regulation of the iron deficiency basic helix-loop-helix transcription factor FIT is affected by iron and nitric oxide. AB - Understanding iron (Fe) sensing and regulation is important for targeting key genes for important nutritional traits like Fe content. The basic helix-loop helix transcription factor FIT (for FER-LIKE FE DEFICIENCY-INDUCED TRANSCRIPTION FACTOR) controls Fe acquisition genes in dicot roots. Posttranscriptional regulation of transcription factors allows rapid adaptation to cellular changes and was also described for FIT. However, the mechanisms behind this regulation of FIT were for a long time not known. Here, we studied the posttranscriptional control mechanisms of FIT in Arabidopsis (Arabidopsis thaliana) and identified nitric oxide as a stabilizing stimulus for FIT protein abundance. Using cycloheximide, we confirmed that the level of FIT protein was regulated by way of protein turnover in wild-type and hemagglutinin-FIT plants. Upon cycloheximide treatment, FIT activity was hardly compromised, since Fe deficiency genes like IRON-REGULATED TRANSPORTER1 and FERRIC REDUCTASE OXIDASE2 were still inducible by Fe deficiency. A small pool of "active" FIT was sufficient for the induction of Fe deficiency downstream responses. Nitric oxide inhibitors caused a decrease of FIT protein abundance and, in the wild type, also a decrease in FIT activity. This decrease of FIT protein levels was reversed by the proteasomal inhibitor MG132, suggesting that in the presence of nitric oxide FIT protein was less likely to be a target of proteasomal degradation. Independent of FIT transcription, FIT protein stability and FIT protein activity, therefore, were targets of control mechanisms in response to Fe and nitric oxide. We summarize our results in a model that explains the different steps of FIT regulation integrating the plant signals that control FIT. PMID- 21972266 TI - Tomato fruit photosynthesis is seemingly unimportant in primary metabolism and ripening but plays a considerable role in seed development. AB - Fruit of tomato (Solanum lycopersicum), like those from many species, have been characterized to undergo a shift from partially photosynthetic to truly heterotrophic metabolism. While there is plentiful evidence for functional photosynthesis in young tomato fruit, the rates of carbon assimilation rarely exceed those of carbon dioxide release, raising the question of its role in this tissue. Here, we describe the generation and characterization of lines exhibiting a fruit-specific reduction in the expression of glutamate 1-semialdehyde aminotransferase (GSA). Despite the fact that these plants contained less GSA protein and lowered chlorophyll levels and photosynthetic activity, they were characterized by few other differences. Indeed, they displayed almost no differences in fruit size, weight, or ripening capacity and furthermore displayed few alterations in other primary or intermediary metabolites. Although GSA antisense lines were characterized by significant alterations in the expression of genes associated with photosynthesis, as well as with cell wall and amino acid metabolism, these changes were not manifested at the phenotypic level. One striking feature of the antisense plants was their seed phenotype: the transformants displayed a reduced seed set and altered morphology and metabolism at early stages of fruit development, although these differences did not affect the final seed number or fecundity. Taken together, these results suggest that fruit photosynthesis is, at least under ambient conditions, not necessary for fruit energy metabolism or development but is essential for properly timed seed development and therefore may confer an advantage under conditions of stress. PMID- 21972268 TI - Neither moxifloxacin nor cefuroxime produces significant attenuation of inflammatory mediator release in patients exposed to cardiopulmonary bypass: a randomized controlled trial. AB - OBJECTIVES: In vitro and experimental studies in animals have established the anti-inflammatory effects of moxifloxacin. Cardiopulmonary bypass (CPB) leads to an inflammatory response. The aim of this study was to assess whether the inflammatory cytokine response to CPB is reduced with a perioperative antibiotic prophylaxis, either moxifloxacin or cefuroxime (the standard prophylaxis). PATIENTS AND METHODS: Twenty-eight patients scheduled for elective coronary artery bypass grafting with CPB were randomly assigned to receive either moxifloxacin or cefuroxime as the perioperative antibiotic prophylaxis. Interleukin (IL)-6, -8, -10 and tumour necrosis factor-alpha (TNF-alpha) serum concentrations were determined at eight time points before and after CPB. RESULTS: In both groups, all cytokine concentrations significantly increased after the start of CPB. There were no statistically significant differences between the moxifloxacin and cefuroxime groups at any point; IL-6 concentrations [median (interquartile range)] 240 min after CPB, the primary endpoint, were 364 (192-598) and 465 (325-906) pg/mL (P = 0.323), respectively. CONCLUSIONS: Neither moxifloxacin nor cefuroxime produced significant attenuation of the inflammatory cytokine response to CPB. The reasons why moxifloxacin did not have significant anti-inflammatory effects in this unique clinical situation may be: (i) the inflammatory response to CPB may be different from that of infectious disease states that were used to establish the immunomodulatory effects of moxifloxacin; and (ii) a single intravenous dose, which was used in this investigation, may not lead to high enough plasma and intracellular concentrations. PMID- 21972267 TI - A comparison of sulfate and selenium accumulation in relation to the expression of sulfate transporter genes in Astragalus species. AB - Sulfate and selenate uptake were investigated in both selenium (Se) hyperaccumulators (Astragalus racemosus and Astragalus bisulcatus) and closely related nonaccumulator species (Astragalus glycyphyllos and Astragalus drummondii). Sulfur (S) starvation increased Se accumulation, whereas increased selenate supply increased sulfate accumulation in both root and shoot tissues. cDNAs for homologs of groups 1 to 4 sulfate transporters were cloned from these Astragalus species to investigate patterns of expression and interactions with sulfate and selenate uptake. In contrast to all other previously analyzed plant species, abundant gene expression of putative sulfate transporters was observed for both Se-hyperaccumulating and nonaccumulating Astragalus, regardless of S and Se status. Furthermore, quantitative analysis of expression indicated a transcript level in Se-hyperaccumulating Astragalus comparable with other plant species under S deprivation. The high expression of sulfate transporters in certain Astragalus species may lead to enhanced Se uptake and translocation ability and therefore may contribute to the Se hyperaccumulation trait; however, it is not sufficient to explain S/Se discriminatory mechanisms. PMID- 21972269 TI - Comparison of European Committee on Antimicrobial Susceptibility Testing (EUCAST) and CLSI screening parameters for the detection of extended-spectrum beta lactamase production in clinical Enterobacteriaceae isolates. AB - OBJECTIVES: To compare the performance of European Committee on Antimicrobial Susceptibility Testing (EUCAST) and CLSI breakpoints following their revision in 2010, for the detection of extended-spectrum beta-lactamase (ESBL) production in Enterobacteriaceae. METHODS: 236 well-characterized clinical isolates (including 118 ESBL producers) were investigated by antibiotic disc testing with cefpodoxime, ceftriaxone, cefepime, cefotaxime EUCAST (5 MUg/disc), ceftazidime EUCAST (10 MUg/disc), cefotaxime CLSI (30 MUg/disc) and ceftazidime CLSI (30 MUg/disc) with the Kirby-Bauer method. Additionally, synergy phenomena were recorded between amoxicillin/clavulanic acid discs (20/10 MUg/disc) and cefepime (30 MUg/disc), EUCAST cefotaxime (5 MUg/disc), EUCAST ceftazidime (10 MUg/disc), CLSI cefotaxime (30 MUg/disc) and CLSI ceftazidime [30 MUg/disc; disc approximation method (DAM)]. RESULTS: Overall sensitivity of the cefotaxime EUCAST non-susceptible breakpoint equalled sensitivity of the cefotaxime CLSI ESBL screening breakpoint (99.2%). With the ceftazidime EUCAST non-susceptible breakpoint, 27/118 ESBL-producing isolates were not detected, whereas the ceftazidime CLSI ESBL screening breakpoint missed 41/118 ESBL-producing isolates. For cefpodoxime the resistant EUCAST breakpoint showed higher sensitivity for ESBL detection compared with the CLSI ESBL screening breakpoint/disc content (100% versus 98.3%, respectively). Sensitivities of ceftazidime and cefotaxime DAM with CLSI or EUCAST disc contents were comparable (sensitivities ranging from 84.7% to 89.8%). DAM with cefepime displayed the highest overall sensitivity (96.6%). In AmpC-producing isolates, synergy of amoxicillin/clavulanic acid with cefepime showed sensitivity and specificity for ESBL detection of 100% and 97.4%, respectively. CONCLUSIONS: EUCAST non-susceptible breakpoints for ceftazidime and cefpodoxime detect more ESBL-producing Enterobacteriaceae isolates compared with corresponding CLSI ESBL screening breakpoints. Implementation of the cefepime DAM can facilitate ESBL screening, especially in strains producing an AmpC beta lactamase since the test shows high sensitivity and specificity. PMID- 21972271 TI - The continuing paradoxes of nursing home policy. PMID- 21972270 TI - In vitro antimicrobial studies of silver carbene complexes: activity of free and nanoparticle carbene formulations against clinical isolates of pathogenic bacteria. AB - OBJECTIVES: Silver carbenes may represent novel, broad-spectrum antimicrobial agents that have low toxicity while providing varying chemistry for targeted applications. Here, the bactericidal activity of four silver carbene complexes (SCCs) with different formulations, including nanoparticles (NPs) and micelles, was tested against a panel of clinical strains of bacteria and fungi that are the causative agents of many skin and soft tissue, respiratory, wound, blood, and nosocomial infections. METHODS: MIC, MBC and multidose experiments were conducted against a broad range of bacteria and fungi. Time-release and cytotoxicity studies of the compounds were also carried out. Free SCCs and SCC NPs were tested against a panel of medically important pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Acinetobacter baumannii (MRAB), Pseudomonas aeruginosa, Burkholderia cepacia and Klebsiella pneumoniae. RESULTS: All four SCCs demonstrated strong efficacy in concentration ranges of 0.5-90 mg/L. Clinical bacterial isolates with high inherent resistance to purified compounds were more effectively treated either with an NP formulation of these compounds or by repeated dosing. Overall, the compounds were active against highly resistant bacterial strains, such as MRSA and MRAB, and were active against the biodefence pathogens Bacillus anthracis and Yersinia pestis. All of the medically important bacterial strains tested play a role in many different infectious diseases. CONCLUSIONS: The four SCCs described here, including their development as NP therapies, show great promise for treating a wide variety of bacterial and fungal pathogens that are not easily killed by routine antimicrobial agents. PMID- 21972272 TI - Clozapine: dangerous orphan or neglected friend? AB - Evidence concerning the superior efficacy and effectiveness of clozapine has not fully informed routine clinical practice. This is possibly because of the perception that clozapine is a dangerous therapeutic agent. Clozapine use may actually promote longevity, and earlier use of clozapine in adequate dosages represents a neglected therapeutic opportunity in this age of stagnated antipsychotic innovation. PMID- 21972273 TI - Circadian rhythms and cognition in schizophrenia. AB - Cognitive impairment is a core feature of schizophrenia. Evidence in this Journal suggests that disrupted circadian synchronisation of sleep-wake phases may be one cause. Circadian synchronisation depends on the external input of light-dark cues and the integrity of central nervous system circadian oscillators; these may represent new interventional targets to improve cognition. PMID- 21972274 TI - The Madrid Declaration: why we need a coordinated Europe-wide effort in mental health research. AB - The Madrid Declaration is being promoted by representatives from seven nationally funded mental health research networks, along with leaders of ongoing European Union-funded mental health projects. It advocates the creation of a Network of Excellent Networks, based on a dynamic and adaptive cross-European network of distinctly qualified research centres. PMID- 21972275 TI - Initiatives to shorten duration of untreated psychosis: systematic review. AB - BACKGROUND: Long duration of untreated psychosis (DUP) is common and associated with poor outcomes. Strategies to enhance early detection of first-episode psychosis have been advocated. AIMS: To evaluate initiatives for early detection of psychosis. METHOD: Systematic review of available evidence on the effectiveness of early detection initiatives to reduce the DUP. RESULTS: The review included 11 studies which evaluated 8 early detection initiatives. Evidence suggests that general practitioner education campaigns and dedicated early intervention services do not by themselves reduce DUP or generate more treated cases. Evidence for multifocus initiatives is mixed: intensive campaigns targeting the general public as well as relevant professionals may be needed. No studies evaluated initiatives targeting young people or professionals from non health organisations. CONCLUSIONS: How early detection can be achieved is not clear. Evidence is most promising for intensive public awareness campaigns: these require organisation and resourcing at a regional or national level. More good-quality studies are needed to address gaps in knowledge. PMID- 21972276 TI - Time course of regional brain activity accompanying auditory verbal hallucinations in schizophrenia. AB - BACKGROUND: The pathophysiology of auditory verbal hallucinations remains poorly understood. AIMS: To characterise the time course of regional brain activity leading to auditory verbal hallucinations. METHOD: During functional magnetic resonance imaging, 11 patients with schizophrenia or schizoaffective disorder signalled auditory verbal hallucination events by pressing a button. To control for effects of motor behaviour, regional activity associated with hallucination events was scaled against corresponding activity arising from random button presses produced by 10 patients who did not experience hallucinations. RESULTS: Immediately prior to the hallucinations, motor-adjusted activity in the left inferior frontal gyrus was significantly greater than corresponding activity in the right inferior frontal gyrus. In contrast, motor-adjusted activity in a right posterior temporal region overshadowed corresponding activity in the left homologous temporal region. Robustly elevated motor-adjusted activity in the left temporal region associated with auditory verbal hallucinations was also detected, but only subsequent to hallucination events. At the earliest time shift studied, the correlation between left inferior frontal gyrus and right temporal activity was significantly higher for the hallucination group compared with non-hallucinating patients. CONCLUSIONS: Findings suggest that heightened functional coupling between the left inferior frontal gyrus and right temporal regions leads to coactivation in these speech processing regions that is hallucinogenic. Delayed left temporal activation may reflect impaired corollary discharge contributing to source misattribution of resulting verbal images. PMID- 21972277 TI - Polygenic dissection of the bipolar phenotype. AB - BACKGROUND: Recent data provide strong support for a substantial common polygenic contribution (i.e. many alleles each of small effect) to genetic susceptibility for schizophrenia and overlapping susceptibility for bipolar disorder. AIMS: To test hypotheses about the relationship between schizophrenia and psychotic types of bipolar disorder. METHOD: Using a polygenic score analysis to test whether schizophrenia polygenic risk alleles, en masse, significantly discriminate between individuals with bipolar disorder with and without psychotic features. The primary sample included 1829 participants with bipolar disorder and the replication sample comprised 506 people with bipolar disorder. RESULTS: The subset of participants with Research Diagnostic Criteria schizoaffective bipolar disorder (n = 277) were significantly discriminated from the remaining participants with bipolar disorder (n = 1552) in both the primary (P = 0.00059) and the replication data-sets (P = 0.0070). In contrast, those with psychotic bipolar disorder as a whole were not significantly different from those with non psychotic bipolar disorder in either data-set. CONCLUSIONS: Genetic susceptibility influences at least two major domains of psychopathological variation in the schizophrenia-bipolar disorder clinical spectrum: one that relates to expression of a 'bipolar disorder-like' phenotype and one that is associated with expression of 'schizophrenia-like' psychotic symptoms. PMID- 21972278 TI - Epilepsy in autism: features and correlates. AB - BACKGROUND: Epilepsy occurs in a significant minority of individuals with autism, but few long-term follow-up studies have been reported, so the prevalence, features (type of seizures, age at onset and severity, etc.) and correlates (IQ history of regression, family history) have only partially been identified. AIMS: To undertake a long-term follow-up study of individuals with autism in order to better characterise the features and correlates of epilepsy in individuals with autism. METHOD: One hundred and fifty individuals diagnosed with autism in childhood were followed up when they were 21+ years of age. All individuals were screened for a history of possible seizures by parental/informant questionnaire. An epilepsy interview was undertaken and medical notes reviewed for individuals with a history of possible seizures. The features and correlates of epilepsy were examined using survival and regression analysis. RESULTS: Epilepsy developed in 22% of participants. In the majority, seizures began after 10 years of age. Generalised tonic-clonic seizures predominated (88%). In over a half (19/33), seizures occurred weekly or less frequently and in the majority of individuals (28/31) they were controlled with the prescription of one to two anticonvulsants. Epilepsy was associated with gender (female), intellectual disability and poorer verbal abilities. Although the presence of epilepsy in the probands was not associated with an increased risk of epilepsy in their relatives, it was associated with the presence of the broader autism phenotype in relatives. This indicates that the familial liability to autism was associated with the risk for epilepsy in the proband. CONCLUSIONS: Epilepsy is an important medical complication that develops in individuals with autism. Seizures may first begin in adolescence or adulthood. Putative risk factors for epilepsy in autism were identified and these will require further investigation in future studies. PMID- 21972279 TI - Childhood eating disorders: British national surveillance study. AB - BACKGROUND: The incidence of eating disorders appears stable overall, but may be increasing in younger age groups. Data on incidence, clinical features and outcome of early-onset eating disorders are sparse. AIMS: To identify new cases of early-onset eating disorders (<13 years) presenting to secondary care over 1 year and to describe clinical features, management and 1-year outcomes. METHOD: Surveillance over 14 months through the established British Paediatric Surveillance System, and a novel child and adolescent psychiatry surveillance system set up for this purpose. RESULTS: Overall incidence was 3.01/100,000 (208 individuals). In total, 37% met criteria for anorexia nervosa; 1.4% for bulimia nervosa; and 43% for eating disorder not otherwise specified. Nineteen per cent showed determined food avoidance and underweight without weight/shape concerns. Rates of comorbidity were 41%; family history of psychiatric disorder 44%; and early feeding difficulties 21%. Time to presentation was >8 months. A total of 50% were admitted to hospital, typically soon after diagnosis. Outcome data were available for 76% of individuals. At 1 year, 73% were reported improved, 6% worse and 10% unchanged (11% unknown). Most were still in treatment, and seven were hospital in-patients for most of the year. CONCLUSIONS: Childhood eating disorders represent a significant clinical burden to paediatric and mental health services. Efforts to improve early detection are needed. These data provide a baseline to monitor changing trends in incidence. PMID- 21972280 TI - Lack of perceived social support among immigrants after a disaster: comparative study. AB - BACKGROUND: Disaster research suggests that immigrant groups who are affected by a disaster receive less emotional support than their native counterparts. However, it is unclear to what extent these differences can be attributed to post-disaster mental health problems or whether they were present before the event. AIMS: To examine the association between lack of social support, immigration status and victim status, as well as differences in support between immigrants and Dutch natives with disaster-related post-traumatic stress disorder (PTSD). METHOD: Social support and psychological distress were assessed among immigrants and Dutch natives, among affected and non-affected individuals 4 years post disaster. Post-traumatic stress disorder was examined in the affected groups. RESULTS: Affected immigrants more often lacked various kinds of perceived social support compared with affected Dutch natives. Remarkably, we found no differences in support between affected immigrants and non-affected immigrants. Immigrants with PTSD differ on only two out of six aspects of support from the Dutch natives with PTSD. CONCLUSIONS: Results clearly indicate that differences in support between immigrants and Dutch natives are not so much a consequence of the disaster but were largely present before the disaster. PMID- 21972281 TI - The classification of psychosis. PMID- 21972282 TI - The classification of psychosis. PMID- 21972283 TI - The classification of psychosis. PMID- 21972285 TI - Theories on the evolutionary persistence of psychosis. PMID- 21972287 TI - Don Quixote and Sancho Panza: folie a deux? PMID- 21972286 TI - Theories on the evolutionary persistence of psychosis. PMID- 21972288 TI - The benefits of an active control arm. PMID- 21972289 TI - ATF5 polymorphisms influence ATF function and response to treatment in children with childhood acute lymphoblastic leukemia. AB - Asparaginase is a standard and critical component in the therapy of childhood acute lymphoblastic leukemia. Asparagine synthetase (ASNS) and the basic region leucine zipper activating transcription factor 5 (ATF5) and arginosuccinate synthase 1 (ASS1) have been shown to mediate the antileukemic effect of asparaginase and to display variable expression between leukemia cells that are resistant and sensitive to treatment. Fourteen polymorphisms in the regulatory and coding regions of these genes were investigated for an association with acute lymphoblastic leukemia outcome. Lower event-free survival (EFS) was associated with ATF5 T1562C, tandem-repeat ASNS polymorphism, derived haplotype, and ASS1 G1343T and G34T substitutions (P <= .03). Associations were limited to patients who received Escherichia coli asparaginase. Variations that sustained correction for multiple testing (ATF5 T1562C, P = .005; ASNS tandem-repeat and related haplotype, P <= .01) were subsequently analyzed in the replication cohort. The E coli-dependent association of the ATF5 T1562 allele with reduced EFS was confirmed (P = .01). A gene-reporter assay showed that the haplotype tagged by T1562 had higher promoter activity (P <= .01). The remaining regulatory polymorphisms also appeared to affect ATF5 function; 2 additional high-activity haplotypes were identified (P <= .02) and were further corroborated by quantitative mRNA analysis in lymphoblastoid cell lines. The ATF5-regulated increase in ASNS expression in response to more efficacious E coli-induced asparagine depletion may explain our observed results. PMID- 21972290 TI - Allo-HLA-reactive T cells inducing graft-versus-host disease are single peptide specific. AB - T-cell alloreactivity directed against non-self-HLA molecules has been assumed to be less peptide specific than conventional T-cell reactivity. A large variation in degree of peptide specificity has previously been reported, including single peptide specificity, polyspecificity, and peptide degeneracy. Peptide polyspecificity was illustrated using synthetic peptide-loaded target cells, but in the absence of confirmation against endogenously processed peptides this may represent low-avidity T-cell reactivity. Peptide degeneracy was concluded based on recognition of Ag-processing defective cells. In addition, because most investigated alloreactive T cells were in vitro activated and expanded, the previously determined specificities may have not been representative for alloreactivity in vivo. To study the biologically relevant peptide specificity and avidity of alloreactivity, we investigated the degree of peptide specificity of 50 different allo-HLA-reactive T-cell clones which were activated and expanded in vivo during GVHD. All but one of the alloreactive T-cell clones, including those reactive against Ag-processing defective T2 cells, recognized a single peptide allo-HLA complex, unique for each clone. Down-regulation of the expression of the recognized Ags using silencing shRNAs confirmed single peptide specificity. Based on these results, we conclude that biologically relevant alloreactivity selected during in vivo immune response is peptide specific. PMID- 21972291 TI - Emergency granulopoiesis promotes neutrophil-dendritic cell encounters that prevent mouse lung allograft acceptance. AB - The mechanisms by which innate immune signals regulate alloimmune responses remain poorly understood. In the present study, we show by intravital 2-photon microscopy direct interactions between graft-infiltrating neutrophils and donor CD11c(+) dendritic cells (DCs) within orthotopic lung allografts immediately after reperfusion. Neutrophils isolated from the airways of lung transplantation recipients stimulate donor DCs in a contact-dependent fashion to augment their production of IL-12 and expand alloantigen-specific IFN-gamma(+) T cells. DC IL 12 expression is largely regulated by degranulation and induced by TNF-alpha associated with the neutrophil plasma membrane. Extended cold ischemic graft storage enhances G-CSF-mediated granulopoiesis and neutrophil graft infiltration, resulting in exacerbation of ischemia-reperfusion injury after lung transplantation. Ischemia reperfusion injury prevents immunosuppression-mediated acceptance of mouse lung allografts unless G-CSF-mediated granulopoiesis is inhibited. Our findings identify granulopoiesis-mediated augmentation of alloimmunity as a novel link between innate and adaptive immune responses after organ transplantation. PMID- 21972292 TI - Molecular dissection of the miR-17-92 cluster's critical dual roles in promoting Th1 responses and preventing inducible Treg differentiation. AB - Mir-17-92 encodes 6 miRNAs inside a single polycistronic transcript, the proper expression of which is critical for early B-cell development and lymphocyte homeostasis. However, during the T-cell antigen response, the physiologic function of endogenous miR-17-92 and the roles of the individual miRNAs remain elusive. In the present study, we functionally dissected the miR-17-92 cluster and revealed that miR-17 and miR-19b are the key players controlling Th1 responses through multiple coordinated biologic processes. These include: promoting proliferation, protecting cells from activation-induced cell death, supporting IFN-gamma production, and suppressing inducible regulatory T-cell differentiation. Mechanistically, we identified Pten (phosphatase and tensin homolog) as the functionally important target of miR-19b, whereas the function of miR-17 is mediated by TGFbetaRII and the novel target CREB1. Because of its vigorous control over the Th1 cell-inducible regulatory T cell balance, the loss of miR-17-92 in CD4 T cells results in tumor evasion. Our results suggest that miR-19b and miR-17 could be harnessed to enhance the efficacy of T cell-based tumor therapy. PMID- 21972293 TI - Positive feedback between PGE2 and COX2 redirects the differentiation of human dendritic cells toward stable myeloid-derived suppressor cells. AB - Dendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) show opposing roles in the immune system. In the present study, we report that the establishment of a positive feedback loop between prostaglandin E(2) (PGE(2)) and cyclooxygenase 2 (COX2), the key regulator of PGE(2) synthesis, represents the determining factor in redirecting the development of CD1a(+) DCs to CD14(+)CD33(+)CD34(+) monocytic MDSCs. Exogenous PGE(2) and such diverse COX2 activators as lipopolysaccharide, IL-1beta, and IFNgamma all induce monocyte expression of COX2, blocking their differentiation into CD1a(+) DCs and inducing endogenous PGE(2), IDO1, IL-4Ralpha, NOS2, and IL-10, typical MDSC-associated suppressive factors. The addition of PGE(2) to GM-CSF/IL-4-supplemented monocyte cultures is sufficient to induce the MDSC phenotype and cytotoxic T lymphocyte (CTL)-suppressive function. In accordance with the key role of PGE(2) in the physiologic induction of human MDSCs, the frequencies of CD11b(+)CD33(+) MDSCs in ovarian cancer are closely correlated with local PGE(2) production, whereas the cancer-promoted induction of MDSCs is strictly COX2 dependent. The disruption of COX2-PGE(2) feedback using COX2 inhibitors or EP2 and EP4 antagonists suppresses the production of MDSC-associated suppressive factors and the CTL-inhibitory function of fully developed MDSCs from cancer patients. The central role of COX2 PGE(2) feedback in the induction and persistence of MDSCs highlights the potential for its manipulation to enhance or suppress immune responses in cancer, autoimmunity, or transplantation. PMID- 21972294 TI - LFA-1 blockade induces effector and regulatory T-cell enrichment in lymph nodes and synergizes with CTLA-4Ig to inhibit effector function. AB - Despite encouraging results using lymphocyte function antigen-1 (LFA-1) blockade to inhibit BM and solid organ transplantation rejection in nonhuman primates and humans, the precise mechanisms underlying its therapeutic potential are still poorly understood. Using a fully allogeneic murine transplantation model, we assessed the relative distribution of total lymphocyte subsets in untreated versus anti-LFA-1-treated animals. Our results demonstrated a striking loss of naive T cells from peripheral lymph nodes, a concomitant gain in blood after LFA 1 blockade, and a shift in phenotype of the cells remaining in the node to a CD62LloCD44hi profile. We determined that this change was due to a specific enrichment of activated, graft-specific effectors in the peripheral lymph nodes of anti-LFA-1-treated mice compared with untreated controls, and not to a direct effect of anti-LFA-1 on CD62L expression. LFA-1 blockade also resulted in a dramatic increase in the frequency of CD4+ FoxP3+ regulatory T cells in graft draining nodes. Our results suggest that the differential impact of LFA-1 blockade on the distribution of naive versus effector and regulatory T cells may underlie its ability to inhibit alloreactive T-cell responses after transplantation. PMID- 21972295 TI - Projected effects of tobacco smoking on worldwide tuberculosis control: mathematical modelling analysis. AB - OBJECTIVES: Almost 20% of people smoke tobacco worldwide--a percentage projected to rise in many poor countries. Smoking has been linked to increased individual risk of tuberculosis infection and mortality, but it remains unclear how these risks affect population-wide tuberculosis rates. DESIGN: We constructed a state transition, compartmental, mathematical model of tuberculosis epidemics to estimate the impact of alternative future smoking trends on tuberculosis control. We projected tuberculosis incidence, prevalence, and mortality in each World Health Organization region from 2010 to 2050, and incorporated changing trends in smoking, case detection, treatment success, and HIV prevalence. RESULTS: The model predicted that smoking would produce an excess of 18 million tuberculosis cases (standard error 16-20) and 40 million deaths from tuberculosis (39-41) between 2010 and 2050, if smoking trends continued along current trajectories. The effect of smoking was anticipated to increase the number of tuberculosis cases by 7% (274 million v 256 million) and deaths by 66% (101 million v 61 million), compared with model predictions that did not account for smoking. Smoking was also expected to delay the millennium development goal target to reduce tuberculosis mortality by half from 1990 to 2015. The model estimated that aggressive tobacco control (achieving a 1% decrease in smoking prevalence per year down to eradication) would avert 27 million smoking attributable deaths from tuberculosis by 2050. However, if the prevalence of smoking increased to 50% of adults (as observed in countries with high tobacco use), the model estimated that 34 million additional deaths from tuberculosis would occur by 2050. CONCLUSIONS: Tobacco smoking could substantially increase tuberculosis cases and deaths worldwide in coming years, undermining progress towards tuberculosis mortality targets. Aggressive tobacco control could avert millions of deaths from tuberculosis. PMID- 21972296 TI - Biobank research: who benefits from individual consent? PMID- 21972297 TI - The cover. The Yerres, effect of rain (L'Yerres, effet de pluie). PMID- 21972298 TI - A piece of my mind. Je vais le faire. PMID- 21972299 TI - IOM review finds vaccine adverse events are rare and usually reversible. PMID- 21972300 TI - Few adults with knee osteoarthritis meet national guidelines for physical activity. PMID- 21972301 TI - Growing list of infections linked to TNF blockers. PMID- 21972302 TI - Evaluating tele-ICU reengineering of critical care processes. PMID- 21972303 TI - Genetic counseling in oncology. PMID- 21972304 TI - Evidence-based practice and health advocacy organizations. PMID- 21972305 TI - Evidence-based practice and health advocacy organizations. PMID- 21972306 TI - Regional variation in the association between advance directives and end-of-life Medicare expenditures. AB - CONTEXT: It is unclear if advance directives (living wills) are associated with end-of-life expenditures and treatments. OBJECTIVE: To examine regional variation in the associations between treatment-limiting advance directive use, end-of-life Medicare expenditures, and use of palliative and intensive treatments. DESIGN, SETTING, AND PATIENTS: Prospectively collected survey data from the Health and Retirement Study for 3302 Medicare beneficiaries who died between 1998 and 2007 linked to Medicare claims and the National Death Index. Multivariable regression models examined associations between advance directives, end-of-life Medicare expenditures, and treatments by level of Medicare spending in the decedent's hospital referral region. MAIN OUTCOME MEASURES: Medicare expenditures, life sustaining treatments, hospice care, and in-hospital death over the last 6 months of life. RESULTS: Advance directives specifying limits in care were associated with lower spending in hospital referral regions with high average levels of end of-life expenditures (-$5585 per decedent; 95% CI, -$10,903 to -$267), but there was no difference in spending in hospital referral regions with low or medium levels of end-of-life expenditures. Directives were associated with lower adjusted probabilities of in-hospital death in high- and medium-spending regions (-9.8%; 95% CI, -16% to -3% in high-spending regions; -5.3%; 95% CI, -10% to 0.4% in medium-spending regions). Advance directives were associated with higher adjusted probabilities of hospice use in high- and medium-spending regions (17%; 95% CI, 11% to 23% in high-spending regions, 11%; 95% CI, 6% to 16% in medium spending regions), but not in low-spending regions. CONCLUSION: Advance directives specifying limitations in end-of-life care were associated with significantly lower levels of Medicare spending, lower likelihood of in-hospital death, and higher use of hospice care in regions characterized by higher levels of end-of-life spending. PMID- 21972307 TI - Hospital-level compliance with asthma care quality measures at children's hospitals and subsequent asthma-related outcomes. AB - CONTEXT: The Children's Asthma Care (CAC) measure set evaluates whether children admitted to hospitals with asthma receive relievers (CAC-1) and systemic corticosteroids (CAC-2) and whether they are discharged with a home management plan of care (CAC-3). It is the only Joint Commission core measure applicable to evaluate the quality of care for hospitalized children. OBJECTIVES: To evaluate longitudinal trends in CAC measure compliance and to determine if an association exists between compliance and outcomes. DESIGN, SETTING, AND PATIENTS: Cross sectional study using administrative data and CAC compliance data for 30 US children's hospitals. A total of 37,267 children admitted with asthma between January 1, 2008, and September 30, 2010, with follow-up through December 31, 2010, accounted for 45,499 hospital admissions. Hospital-level CAC measure compliance data were obtained from the National Association of Children's Hospitals and Related Institutions. Readmission and postdischarge emergency department (ED) utilization data were obtained from the Pediatric Health Information System. MAIN OUTCOME MEASURES: Children's Asthma Care measure compliance trends; postdischarge ED utilization and asthma-related readmission rates at 7, 30, and 90 days. RESULTS: The minimum quarterly CAC-1 and CAC-2 measure compliance rates reported by any hospital were 97.1% and 89.5%, respectively. Individual hospital CAC-2 compliance exceeded 95% for 97.9% of the quarters. Lack of variability in CAC-1 and CAC-2 compliance precluded examination of their association with the specified outcomes. Mean CAC-3 compliance was 40.6% (95% CI, 34.1%-47.1%) and 72.9% (95% CI, 68.8%-76.9%) for the initial and final 3 quarters of the study, respectively. The mean 7-, 30-, and 90-day postdischarge ED utilization rates were 1.5% (95% CI, 1.3%-1.6%), 4.3% (95% CI, 4.0%-4.5%), and 11.1% (95% CI, 10.5%-11.7%) and the mean quarterly 7-, 30-, and 90-day readmission rates were 1.4% (95% CI, 1.2%-1.6%), 3.1% (95% CI, 2.8%-3.3%), and 7.6% (95% CI, 7.2%-8.1%). There was no significant association between overall CAC-3 compliance (odds ratio [OR] for 5% improvement in compliance) and postdischarge ED utilization rates at 7 days (OR, 1.00; 95% CI, 0.98-1.02), 30 days (OR, 0.97; 95% CI, 0.90-1.04), and 90 days (OR, 0.96; 95% CI, 0.77-1.18). In addition, there was no significant association between overall CAC-3 compliance (OR for 5% improvement in compliance) and readmission rates at 7 days (OR, 1.00; 95% CI, 0.99-1.02), 30 days (OR, 0.99; 95% CI, 0.96-1.02), and 90 days (OR, 1.01; 95% CI, 0.90-1.12). CONCLUSION: Among children admitted to pediatric hospitals for asthma, there was high hospital-level compliance with CAC-1 and CAC-2 quality measures and moderate compliance with the CAC-3 measure but no association between CAC-3 compliance and subsequent ED visits and asthma-related readmissions. PMID- 21972308 TI - Prevalence and outcomes of same-day discharge after elective percutaneous coronary intervention among older patients. AB - CONTEXT: Patients undergoing elective percutaneous coronary intervention (PCI) are generally observed overnight in the hospital. The association between same day discharge of older patients and death or readmission is unclear. OBJECTIVE: To evaluate the prevalence and outcomes of same-day discharge among older patients undergoing elective PCI in the United States. DESIGN, SETTING, AND PARTICIPANTS: Multicenter cohort study. Data were from 107,018 patients 65 years or older undergoing elective PCI procedures at 903 sites participating in the CathPCI Registry between November 2004 and December 2008 and were linked with Medicare Part A claims. Patients were divided into 2 groups based on their length of stay after PCI: same-day discharge or overnight stay. MAIN OUTCOME MEASURES: Death or rehospitalization occurring within 2 days and by 30 days after PCI. RESULTS: The prevalence of same-day discharge was 1.25% (95% CI, 1.19%-1.32%; n = 1339 patients) with significant variation across facilities. Patient characteristics were similar between the 2 groups, although same-day discharge patients underwent shorter procedures with less multivessel intervention. There were no significant differences in the rates of death or rehospitalization at 2 days (same-day discharge, 0.37% [95% CI, 0.16%-0.87%] vs overnight stay, 0.50% [95% CI, 0.46%-0.54%]; P = .51) or at 30 days (same-day discharge, 9.63% [95% CI, 8.17%-11.33%] vs overnight stay, 9.70% [95% CI, 9.52%-9.88%]; P = .94). Among patients with adverse outcomes, the median time to death or rehospitalization did not differ significantly between the groups (same-day discharge, 13 days [interquartile range, 7.0-21.0] vs overnight stay, 14 days [interquartile range, 7.0-21.0]; P = .96). After adjustment for patient and procedure characteristics, same-day discharge was not significantly associated with 30-day death or rehospitalization (adjusted odds ratio, 0.95 [95% CI, 0.78-1.16]). CONCLUSION: Among selected low-risk Medicare patients undergoing elective PCI, same-day discharge is rarely implemented but is not associated with death or rehospitalization compared with overnight observation. PMID- 21972309 TI - The physician's role in patients' nursing home care: "She's a very courageous and lovely woman. I enjoy caring for her". AB - More than 1.5 million adults live in US nursing homes, and approximately 30% of individuals in the United States will die with a nursing home as their last place of residence. Physicians play a pivotal role in the rehabilitation, complex medical care, and end-of-life care of this frail and vulnerable population. The reasons for admission are multifactorial and a comprehensive care plan based on the Minimum Data Set guides the multidisciplinary nursing home team in the care of the patient and provides assessments of the quality of care provided. Using the cases of 2 patients with different experiences, we describe the physician's role in planning for admission, participating as a team member in the ongoing assessment and care in the nursing home, and guiding care at the end of life. The increasing population of older adults has also promoted community-based and residential alternatives to traditional nursing homes. The future of long-term care will include additional challenges and rich innovations in services and options for older adults. PMID- 21972310 TI - The medical benefits of male circumcision. PMID- 21972311 TI - Quality indicators for older adults: preventing unintended harms. PMID- 21972312 TI - Time-limited trials near the end of life. PMID- 21972313 TI - The evolution of advance directives. PMID- 21972314 TI - Improving improvement for childhood asthma. PMID- 21972315 TI - JAMA patient page. Irritable bowel syndrome. PMID- 21972324 TI - Type D personality and vulnerability to adverse outcomes in heart disease. AB - General distress, shared across depression, anxiety and anger, partly accounts for the link between mind and heart. The type D (distressed) personality profile identifies individuals who are particularly vulnerable to the adverse effect of general distress. Type D individuals frequently experience negative emotions and are socially inhibited. This profile is more stable than that associated with episodes of clinical depression and describes the chronic nature of distress in some patients. Type D may also partly account for the effect of emotional distress on cardiac prognosis. Type D is associated with a threefold increased risk of adverse cardiovascular outcomes, even after adjustment for depression. This relationship is less obvious in patients with heart failure. Plausible pathways linking type D to cardiovascular complications include hypothalamic pituitary-adrenal-axis hyperreactivity, autonomic and inflammatory dysregulation, and increased oxidative stress. Research needs to further clarify these pathways and investigate whether type D patients may benefit from closer monitoring of risk factors and a personalized approach to behavioral intervention. The DS14 is a brief, well-validated measure of type D that could be incorporated into clinical research and practice to identify high-risk patients. PMID- 21972325 TI - Biofeedback in the treatment of heart disease. AB - Biofeedback is a method of training subjects to regulate their own physiology using feedback from physiologic sensors connected to an output display. Biofeedback-assisted stress management (BFSM) incorporates the physiologic signals with instructions on stress management. The goal of BFSM training is to give subjects the tools to control their own mental and physiologic reactions, leading to improved health and wellness. In cardiovascular disease, overactivation of the sympathetic component of the autonomic nervous system and psychologic stress together negatively affect quality of life and clinical status. BFSM targets both areas. We hypothesize that this intervention can be used in cardiovascular disease to improve clinical status and quality of life, as well as interfere with disease progression. We are conducting trials of BFSM in heart failure and stable coronary artery disease. Preliminary data suggest that use of BFSM by heart failure patients may actually cause cellular and molecular remodeling of the failing heart in the direction of normal. We are comparing the effects of BFSM with usual care in patients with stable coronary artery disease, testing the hypothesis that the intervention will decrease both sympathetic hyperarousal and activation of the inflammatory cascade. Since heart rate variability is abnormal in both cardiovascular disease and depression, and since BFSM has been successfully used to change heart rate variability, we also expect this intervention to have a positive impact on the depression that often accompanies cardiovascular disease. PMID- 21972326 TI - Electrical vagus nerve stimulation for the treatment of chronic heart failure. AB - Autonomic dysregulation is a feature of chronic heart failure (HF) and is characterized by a sustained increase of sympathetic drive and by withdrawal of parasympathetic activity. Both sympathetic overdrive and increased heart rate are predictors of poor long-term outcome in patients with HF. Pharmacologic agents that partially inhibit sympathetic activity, such as beta-adrenergic receptor blockers, effectively reduce mortality and morbidity in patients with chronic HF. In contrast, modulation of parasympathetic activation as a potential therapy for HF has received only limited attention because of its inherent complex cardiovascular effects. This review examines results of experimental animal studies that provide support for the possible use of electrical vagus nerve stimulation (VNS) as a long-term therapy for the treatment of chronic HF. The review also addresses the effects of VNS on potential modifiers of the HF state, including proinflammatory cytokines, nitric oxide elaboration, and myocardial expression of gap junction proteins. Finally, the safety, feasibility, and efficacy trends of VNS in patients with advanced HF are reviewed. PMID- 21972327 TI - Treatment of chronic inflammatory diseases with implantable medical devices. AB - Implantable medical devices are finding increasing use in the treatment of diseases traditionally targeted with drugs. It is well established that the cholinergic anti-inflammatory pathway serves as a physiological regulator of inflammatory responses, but stimulation of this pathway therapeutically by electrical stimulation of the vagus nerve can also diminish excessive or dysregulated states of inflammation. Recent data from a wide variety of animal models, as well as evidence of reduced vagal tone in rheumatoid arthritis and other inflammatory diseases, support the rationale for, and feasibility of, developing implantable vagal nerve stimulation devices to treat chronic inflammation in humans. PMID- 21972329 TI - The Bypassing the Blues trial: collaborative care for post-CABG depression and implications for future research. AB - Depressive symptoms are reported by up to one-half of patients following coronary artery bypass graft (CABG) surgery, and are associated with numerous adverse outcomes, including poorer health-related quality of life, worse functional status, and delayed recovery. Strategies to detect and then manage depression in CABG patients and in cardiac populations are of great interest given the potential for depression treatment to reduce cardiovascular morbidity. Yet, many tested interventions have had little or no effect on mood symptoms in cardiac patients. "Collaborative care" is a safe and proven-effective strategy for treating depression in concert with patients' primary care physicians; however, it had not been tested previously in patients with cardiac disease. This article presents the design and main outcome findings from the National Institutes of Health-funded Bypassing the Blues study, the first trial to examine the impact of a collaborative care strategy for treating depression among patients with cardiac disease, and our efforts to improve upon and expand the model for testing in other cardiac conditions. PMID- 21972328 TI - New frontiers in cardiovascular behavioral medicine: comparative effectiveness of exercise and medication in treating depression. AB - Exercise, considered a mainstay of cardiac rehabilitation, has been shown to reduce cardiac risk factors such as hyperlipidemia and hypertension. Growing evidence also suggests that exercise has beneficial effects on mental health, which is relevant for cardiac patients because of the prognostic significance of depression in patients with coronary heart disease (CHD). Depression has been associated with increased mortality and nonfatal cardiac events in patients with CHD; it is also associated with worse outcomes in patients who undergo coronary artery bypass graft surgery and those who have heart failure. The standard therapy for depression is pharmacologic treatment, often with second-generation antidepressants such as selective serotonin reuptake inhibitors. Despite their widespread use, antidepressants have only modest effects on depression for many patients compared with placebo controls. Exercise therapy, already an established component of cardiac rehabilitation, has potential efficacy as a treatment for depression in cardiac disease patients. Randomized controlled trials are needed to determine the clinical effects of exercise in this population and to compare the effects of exercise with those of antidepressants. PMID- 21972330 TI - Depression: a shared risk factor for cardiovascular and Alzheimer disease. AB - Depression has been linked to cardiovascular disease and cognitive impairment, including Alzheimer disease, but the exact nature of the relationship is poorly understood. Although depression seems to progress little after the onset of Alzheimer disease, depression in earlier life increases the risk of dementia and cognitive impairment many years in the future. Depression is also associated with reduced vascular function and is a poorly recognized but significant risk factor for stroke. PMID- 21972331 TI - Inflammatory signaling in Alzheimer disease and depression. AB - To help define the relationships among inflammation, Alzheimer disease, and depression, the Texas Alzheimer's Research Consortium analyzed an array of inflammatory biomarkers in a cohort of patients with Alzheimer disease and in controls. Inflammation severity was highly correlated with earlier age at onset of Alzheimer disease and was also associated with cognitive decline. The relationship between inflammation and depression was not as clear, and it varied with aspects of depression, gender, and the presence of Alzheimer disease. PMID- 21972332 TI - Vascular signaling abnormalities in Alzheimer disease. AB - Our laboratory has documented that brain microvessels derived from patients with Alzheimer disease (AD) express or release a myriad of factors that have been implicated in vascular activation and angiogenesis. In addition, we have documented that signaling cascades associated with vascular activation and angiogenesis are upregulated in AD-derived brain microvessels. These results are consistent with emerging data suggesting that factors and processes characteristic of vascular activation and angiogenesis are found in the AD brain. Despite increases in proangiogenic factors and signals in the AD brain, however, evidence for increased vascularity in AD is lacking. Cerebral hypoperfusion/hypoxia, a potent stimulus for vascular activation and angiogenesis, triggers hypometabolic, cognitive, and degenerative changes in the brain. In our working model, hypoxia stimulates the angiogenic process; yet, there is no new vessel growth. Therefore, there are no feedback signals to shut off vascular activation, and endothelial cells become irreversibly activated. This activation results in release of a large number of proteases, inflammatory proteins, and other gene products with biologic activity that can injure or kill neurons. Pathologic activation of brain vasculature may contribute noxious mediators that lead to neuronal injury and disease processes in AD brains. This concept is supported by preliminary experiments in our laboratory, which show that pharmacologic blockade of vascular activation improves cognitive function in an animal model of AD. Thus, "vascular activation" could be a novel, unexplored therapeutic target in AD. PMID- 21972333 TI - Stress in medicine: strategies for caregivers, patients, clinicians. PMID- 21972334 TI - Key 2010 publications in behavioral medicine. AB - Previous research has demonstrated an association between depression and incident coronary heart disease (CHD); in 2010, well-controlled studies and meta-analyses went beyond depression to include anxiety, anger expression, and negative affect as predictors of incident CHD. Emerging research suggests that positive emotions and resilience (including the ability to self-regulate) offer protection against CHD. New research is elucidating the pathophysiology to explain the effects of emotion and resilience on disease risk; for example, recent work has begun to consider how the relaxation response promotes resilience and found that it induces genomic changes that counter oxidative stress and associated cellular damage. PMID- 21972335 TI - Imaging for autonomic dysfunction. AB - Direct visualization of heart-brain interactions is the goal when assessing autonomic nervous system function. Cortical topology relevant to neuroimaging consists of the cingulate, insula, and amygdala, all of which share proximity to the basal ganglia. Significant cardiac effects stemming from brain injury are well known, including alteration of cardiac rhythms, cardiac variability, and blood pressure regulation; in some instances, these effects may correlate with neuroimaging, depending on the region of the brain involved. It is difficult to achieve visualization of areas within the brainstem that govern autonomic responses, although investigators have identified brain correlates of autonomic function with the use of functional magnetic resonance imaging and electrocardiographic data obtained simultaneously. The potential utility of brain imaging in sick patients may be limited because of challenges such as the magnetic resonance imaging environment and blunted autonomic responses, but continued investigation is warranted. PMID- 21972336 TI - Neurohormonal control of heart failure. AB - For nearly three decades, starting in the early 1970s, the cardiology research laboratories at the University of Minnesota served as the focal point for the discovery and implementation of much of the information we now apply to the management of heart failure. Director Jay Cohn, building on his expertise in hypertension and hemodynamics, led many creative and committed investigators in the exploration of the mechanisms responsible for increased sensitivity to afterload in heart failure. The neurohormonal hypothesis of heart failure led to the development of several pharmacologic tools, such as angiotensin-converting enzyme inhibitors, beta-adrenergic blockers, and, later, angiotensin-receptor blockers. By the late 1990s, it was understood that neurohormonal antagonists could prevent the progression of left ventricular remodeling and favorably influence the natural history of heart failure. Neurohormonal blockers are now considered standard therapy. Issues remain to be addressed, including early identification and treatment of patients at risk. PMID- 21972375 TI - Chest ultrasonography: where's the beef? PMID- 21972376 TI - The elderly are different: resection for non-small cell lung cancer. PMID- 21972377 TI - Reengineering health care via medical simulation tools: "Lions and tigers and bears. Oh my!". PMID- 21972378 TI - Clinical management of atrial fibrillation: need for a comprehensive patient centered approach. PMID- 21972379 TI - Point: Should tele-ICU services be eligible for professional fee billing? Yes. Tele-ICUs and the triple aim. PMID- 21972380 TI - Counterpoint: Should tele-ICU services be eligible for professional fee billing? No. PMID- 21972381 TI - Simulation to enhance patient safety: why aren't we there yet? AB - The delivery of state-of-the-art medical care is complex, with large numbers of treatment strategies often available to individual patients. It is paramount to ensure that each patient receives optimal treatment in a safe, effective, and timely manner. Evidence suggests that an unacceptably high number of patients currently experience suboptimal care as the result of adverse events and medical error. Simulation-based training reduces medical error, enhances clinical outcomes, and reduces the cost of clinical care. It is surprising that medical simulation is not routinely integrated into the training curricula of all health care professionals. Simulation enables doctors to practice and hone their technical, communication, decision making, and crisis management skills in a safe and educationally orientated environment. The process can foster the development of interprofessional working skills, leading to enhanced patient outcomes. Selection, credentialing, and revalidation of medical professionals are also possible in a simulation setting, enabling maintenance of standards of practice throughout a medical career. In order for simulation to become a part of the medical curriculum, collaborative efforts are required from academics, physicians, managers, and policy makers alike. Bringing these groups together, while a challenge, can lead to high-level outputs in medical care, which will benefit all. PMID- 21972382 TI - Transient receptor potential A1 channels: insights into cough and airway inflammatory disease. AB - Cough is a common symptom of diseases such as asthma and COPD and also presents as a disease in its own right. Treatment options are limited; a recent meta analysis concluded that over-the-counter remedies are ineffective, and there is increasing concern about their use in children. Transient receptor potential cation channel, subfamily A, member 1 (TRPA1) channels are nonselective cation channels that are activated by a range of natural products (eg, allyl isothiocyanate), a multitude of environmental irritants (eg, acrolein, which is present in air pollution, vehicle exhaust, and cigarette smoke), and inflammatory mediators (eg, cyclopentenone prostaglandins). TRPA1 is primarily expressed in small-diameter, nociceptive neurons where its activation probably contributes to the perception of noxious stimuli. Inhalational exposure to irritating gases, fumes, dusts, vapors, chemicals, and endogenous mediators can lead to the development of cough. The respiratory tract is innervated by primary sensory afferent nerves, which are activated by mechanical and chemical stimuli. Recent data suggest that activation of TRPA1 on these vagal sensory afferents by these irritant substances could lead to central reflexes, including dyspnea, changes in breathing pattern, and cough, which contribute to the symptoms and pathophysiology of respiratory diseases. PMID- 21972384 TI - Bronchodilator reversibility in COPD. AB - COPD is a preventable and treatable disease characterized by airflow limitation that is not fully reversible. The diagnosis of COPD is based on spirometric evidence of airways obstruction following bronchodilator administration. Although it used to be commonly believed that patients with COPD have largely irreversible airflow obstruction, evidence now suggests that a considerable proportion of patients exhibit clinically significant bronchodilator reversibility. The complexity and inherent variability of a patient's acute response to a bronchodilator and the lack of a standardized procedure for assessing bronchodilator reversibility have led to significant confusion surrounding this concept. Although bronchodilator reversibility commonly is defined based on thresholds for improvement in FEV(1), lung volume-based measures of pulmonary function may be of particular importance in patients with severe COPD. The usefulness of acute reversibility to short-acting bronchodilators in predicting a patient's long-term response to bronchodilator maintenance therapy is also unclear, although most studies suggest that a lack of acute response to short acting bronchodilators does not preclude a beneficial long-term response to maintenance bronchodilator treatment. This review outlines recent findings about the prevalence and usefulness of bronchodilator reversibility in patients with COPD based on the available literature and proposes areas of future research. PMID- 21972383 TI - New kids on the block: the emerging role of apolipoproteins in the pathogenesis and treatment of asthma. AB - New treatments are needed for patients with severe asthma. We hypothesized that a clinically relevant experimental model of house dust mite (HDM)-induced murine asthma could be used to discover new pathways that regulate disease severity. In HDM-challenged mice, genome-wide expression profiling of the asthmatic lung transcriptome identified apolipoprotein E (apoE) as a steroid-unresponsive gene with persistently upregulated expression despite dexamethasone treatment. ApoE and low-density lipoprotein receptor (LDLR) knockout mice were used to demonstrate that apoE, which is produced by lung macrophages, functions in a paracrine fashion by binding to LDLRs expressed on ciliated airway epithelial cells, to negatively modulate airway hyperreactivity, mucin gene expression, and goblet cell hyperplasia. Furthermore, administration of an apoE mimetic peptide, which corresponded to the LDLR-binding domain of apoE, prevented the induction of airway inflammation, airway hyperreactivity, and goblet cell hyperplasia in HDM challenged apoE knockout mice. This suggests that therapeutic strategies that activate the apoE-LDLR pathway, such as apoE mimetic peptides, may represent a novel treatment approach for patients with asthma. Similarly, we showed that administration of a 5A apolipoprotein A-I mimetic peptide attenuated the induction of HDM-mediated asthma in mice. These preclinical data suggest that apoE and apoA-I mimetic peptides might be developed into alternative treatments for patients with severe asthma. Future clinical trials will be required to determine whether inhaled apolipoprotein E or apolipoprotein A-I mimetic peptides are effective for the treatment of severe asthma, including patients with phenotypes that lack effective therapeutic options. PMID- 21972385 TI - Chylothorax caused by Paragonimus westermani in a native Californian. AB - Paragonimiasis is a parasitic infection endemic in Asia but uncommon in the United States. It presents most frequently with cough and hemoptysis. Pleural effusions are common and can manifest occasionally as a pseudochylothorax, but a true chylothorax has, to our knowledge, never been reported. We report a case of a chylothorax from infection with Paragonimus westermani. The case is also unique because it occurred in a native Californian who had not traveled to Asia and was infected by eating raw crabs at a local sushi restaurant. The freshwater crabs had been imported from Asia. PMID- 21972386 TI - Pulmonary arterial hypertension in a patient with Cowden syndrome and anorexigen exposure. AB - We report a case of pulmonary arterial hypertension (PAH) occurring in a patient with Cowden syndrome with a mutation in the phosphatase and tensin (PTEN) tumor suppressor gene, in the context of exposure to the appetite suppressant dexfenfluramine. Anorexigen exposure is known to be a risk factor for PAH. However, the role of PTEN in cell function and the development of pulmonary vascular remodeling and histopathologic signs of PAH in mice with a Pten depletion in smooth muscle cells suggest that the association of PAH and Cowden syndrome may be relevant. In this case report, we hypothesize that PTEN mutations may be a predisposing factor for the development of PAH, with anorexigen exposure as a potential trigger. PMID- 21972387 TI - Asthma unmasked with tumor necrosis factor-alpha-blocking drugs. AB - We report five cases of asthma unmasked by anti-tumor necrosis factor (TNF)-alpha blocking drugs. Asthma symptoms appeared within an average of 4 months (range 1 24 months) after starting the anti-TNF-alpha treatment for inflammatory disease. The patients did not appear to be predisposed to asthma except for one patient who had asthma during childhood. Four patients stopped anti-TNF-alpha-blocking drugs with an improvement of symptoms within 1 to 5 months. In the patient with a history of childhood asthma, respiratory symptoms recurred when another anti-TNF alpha therapy was started. Asthma control was achieved with inhaled steroids, allowing anti-TNF-alpha treatment to continue. The biotherapy was maintained for the fifth patient in association with inhaled steroids. The pathophysiologic mechanisms are unknown but are probably more complex than the T helper 1/T helper 2 imbalance suggested in the literature, and further studies are required. PMID- 21972388 TI - Toxicology in the ICU: Part 2: specific toxins. AB - This is the second of a three-part series that reviews the generalized care of poisoned patients in the ICU. This article focuses on specific agents grouped into categories, including analgesics, anticoagulants, cardiovascular drugs, dissociative agents, carbon monoxide, cyanide, methemoglobinemia, cholinergic agents, psychoactive medications, sedative-hypnotics, amphetamine-like drugs, toxic alcohols, and withdrawal states. The first article discussed the general approach to the toxicology patient, including laboratory testing; the third article will cover natural toxins. PMID- 21972389 TI - Pulmonary hypertension presenting with apnea, cyanosis, and failure to thrive in a young child. PMID- 21972390 TI - Recurrent sepsis in a 69-year-old woman. PMID- 21972391 TI - Anesthesiologists and obstructive sleep apnea: simple things may still work. PMID- 21972392 TI - Metal particles and endobronchial ultrasound needles. PMID- 21972393 TI - Why conventional exhaled breath condensate pH studies cannot provide reliable estimates of airway acidification. PMID- 21972394 TI - Probiotics in united airways disease. PMID- 21972395 TI - Tako-tsubo cardiomyopathy: is a temporal pattern of onset confirmed? PMID- 21972396 TI - First influenza season outbreak after 2009 pandemic influenza A(H1N1) in Spain. PMID- 21972397 TI - Which mask for noninvasive ventilation in acute respiratory failure? PMID- 21972398 TI - BAL fluid surfactant protein C level is related to parenchymal lung disease in children with sarcoidosis. PMID- 21972399 TI - Detection of lipid-core plaques by intracoronary near-infrared spectroscopy identifies high risk of periprocedural myocardial infarction. AB - BACKGROUND: Percutaneous coronary intervention (PCI) is associated with periprocedural myocardial infarction (MI) in 3% to 15% of cases (depending on the definition used). In many cases, these MIs result from distal embolization of lipid-core plaque (LCP) constituents. Prospective identification of LCP with catheter-based near-infrared spectroscopy (NIRS) may predict an increased risk of periprocedural MI and facilitate development of preventive measures. METHODS AND RESULTS: The present study analyzed the relationship between the presence of a large LCP (detected by NIRS) and periprocedural MI. Patients with stable preprocedural cardiac biomarkers undergoing stenting were identified from the COLOR Registry, an ongoing prospective observational study of patients undergoing NIRS before PCI. The extent of LCP in the treatment zone was calculated as the maximal lipid-core burden index (LCBI) measured by NIRS for each of the 4-mm longitudinal segments in the treatment zone. A periprocedural MI was defined as new cardiac biomarker elevation above 3* upper limit of normal. A total of 62 patients undergoing stenting met eligibility criteria. A large LCP (defined as a maxLCBI(4 mm) >=500) was present in 14 of 62 lesions (22.6%), and periprocedural MI was documented in 9 of 62 (14.5%) of cases. Periprocedural MI occurred in 7 of 14 patients (50%) with a maxLCBI(4 mm) >=500, compared with 2 of 48 patients (4.2%) patients with a lower maxLCBI(4 mm) (P=0.0002). CONCLUSIONS: NIRS provides rapid, automated detection of extensive LCPs that are associated with a high risk of periprocedural MI, presumably due to embolization of plaque contents during coronary intervention. PMID- 21972400 TI - Vascular responses to drug-eluting and bare metal stents in diabetic/hypercholesterolemic and nonatherosclerotic porcine coronary arteries. AB - BACKGROUND: Animal models used to gain insight into the vascular response to drug eluting stents are generally juvenile and nonatherosclerotic, whereas stents are placed in patients with complex atherosclerosis and comorbidities. Hence, models reflecting these complexities are needed to help elucidate the vascular effects of drug-eluting stents. We compared the vascular responses with bare metal stent (BMS) and paclitaxel-eluting stent (PES) implantation in a diabetic/hypercholesterolemic (DM/HC) porcine model of advanced coronary atherosclerosis with the standard juvenile porcine model. METHODS AND RESULTS: Two studies using similar stent procedural protocols were performed in either DM/HC (n=20) or domestic swine (non-DM/HC, n=20). Animals pretreated with dual antiplatelet therapy, underwent BMS or PES implantation (1/artery, 2 stents per animal) and were euthanized 30 or 90 days later. DM/HC resulted in a 24% increase in platelet aggregation (P=0.05 versus baseline), whereas dual-antiplatelet therapy reduced platelet aggregation in both groups (P<0.0001). DM/HC pigs developed substantially greater neointimal area versus non-DM/HC pigs, regardless of stent type, (P=0.004 for BMS at 30 days and P=0.002 at 90 days, P=0.005 for PES at 30 days, P=0.002 at 90 days). Compared with non-DM/HC pigs, reendothelialization was delayed in DM/HC pigs, more so after PES implantation. Increased para-strut leukocytes were observed for PES compared with BMS in the DM/HC pigs at both 30 days (P=0.023) and 90 days (P=0.04). As well, increased T lymphocyte infiltration was seen in the DM/HC pigs. CONCLUSIONS: Stent implantation in a DM/HC swine model provides a metabolic environment closer to human disease, including hyperglycemia, hypercholesterolemia, and increased platelet aggregation. This model augmented differences in the vascular response between PES and BMS that are not as clearly evident in the non-DM/HC swine, including increased neointimal area, delayed reendothelialization, and greater, persistent vascular inflammation. PMID- 21972401 TI - Bleeding risk comparing targeted low-dose heparin with bivalirudin in patients undergoing percutaneous coronary intervention: results from a propensity score matched analysis of the Evaluation of Drug-Eluting Stents and Ischemic Events (EVENT) registry. AB - BACKGROUND: Prior randomized trials have shown reduced bleeding with bivalirudin compared with unfractionated heparin (UFH) in patients undergoing percutaneous coronary intervention (PCI). However, it is not known if this benefit is also present when UFH doses are more tightly controlled (as measured by activated clotting time, ACT). METHODS AND RESULTS: Patients enrolled in the EVENT (Evaluation of Drug-Eluting Stents and Ischemic Events) registry, were divided into 3 groups, based on the antithrombotic drug used during PCI (UFH monotherapy, UFH+glycoprotein IIb-IIIa receptor inhibitor [GPI], or bivalirudin alone). Propensity score matching was used to adjust for measured covariates (89 variables) and to compare bivalirudin versus UFH monotherapy and bivalirudin versus UFH+GPI groups. The UFH groups were stratified based on ACT achieved (optimal ACT defined as 250-300 for UFH monotherapy and 200-250 when GPI was also used). The primary bleeding outcome was in-hospital composite bleeding, defined as events of access site bleeding, Thrombolysis In Myocardial Infarction major/minor bleeding, or transfusion. Primary (in-hospital death/myocardial infarction) and secondary ischemic outcomes (death/MI/unplanned repeat revascularization at 12 months) were also evaluated. Propensity score matching yielded 3022 patients for the UFH monotherapy versus bivalirudin comparison and 3520 patients for the UFH+GPI versus bivalirudin comparison. Bivalirudin use was associated with numerically lower bleeding rates at all categories of achieved ACT when compared with UFH (low, optimal, high ACT: 2.5% versus 4.7%, 1.9% versus 6.0%, 3.1% versus 4.8%, respectively) or heparin+GPI groups (low, optimal, high ACT: 0.0% versus 2.7%, 2.7% versus 5.2%, 2.4% versus 6.1%, respectively) and was not associated with any statistically significant increase in either primary or secondary ischemic outcomes. CONCLUSIONS: Among unselected patients undergoing PCI, bivalirudin use during PCI was associated with a lower risk of bleeding at all comparator ACT levels without an increase in ischemic outcomes. PMID- 21972402 TI - Prognostic implications of creatine kinase-MB elevation after percutaneous coronary intervention: results from the Evaluation of Drug-Eluting Stents and Ischemic Events (EVENT) registry. AB - BACKGROUND: Creatine kinase-MB (CK-MB) elevation after percutaneous coronary intervention (PCI) has been associated with increased risk for mortality. Although most studies have defined periprocedural myocardial infarction (pMI) as an elevation in CK-MB >3* upper limit of normal (ULN), use of different CK-MB assays and variation in site-specific definitions of the ULN may limit the value of such relative thresholds. METHODS AND RESULTS: We used data from the multicenter Evaluation of Drug-Eluting Stents and Ischemic Events (EVENT) registry to examine the impact of variations in site-specific thresholds for CK MB elevation on the incidence of pMI as well as the relationship between absolute peak levels of CK-MB after PCI and 1-year mortality. The study cohort consisted of 6347 patients who underwent nonemergent PCI and had normal CK-MB at baseline. Across the 59 study centers, the ULN for CK-MB ranged from 2.6 to 10.4 ng/mL (median, 5.0 ng/mL), and there was an inverse relationship between the site specific ULN and the incidence of pMI (defined as CK-MB elevation >3* ULN). Although any postprocedure elevation of CK-MB was associated with an adverse prognosis, in categorical analyses, only CK-MB >=50 ng/mL was independently associated with increased 1-year mortality (hazard ratio, 4.71; 95% confidence interval, 2.42 to 9.13; P<0.001). Spline analysis using peak CK-MB as a continuous variable suggested a graded, nonlinear relationship with 1-year mortality, with an inflection point at ~30 ng/mL. CONCLUSIONS: Among unselected patients undergoing PCI, there is a graded relationship between CK-MB elevation after PCI and 1-year mortality that is particularly strong for large CK-MB elevations (>30 to 50 ng/mL). Future studies that include pMI as a clinical end point should consider using a core laboratory to assess CK-MB (to ensure consistency) and raising the threshold for defining pMI above current levels (to enhance clinical relevance). PMID- 21972403 TI - Effects of hydration in contrast-induced acute kidney injury after primary angioplasty: a randomized, controlled trial. AB - BACKGROUND: Intravascular volume expansion represents a beneficial measure against contrast-induced acute kidney injury (CI-AKI) in patients undergoing elective angiographic procedures. However, the efficacy of this preventive strategy has not yet been established for patients with ST-elevation-myocardial infarction (STEMI), who are at higher risk of this complication after primary percutaneous coronary intervention (PCI). In this randomized study we investigated the possible beneficial role of periprocedural intravenous volume expansion and we compared the efficacy of 2 different hydration strategies in patients with STEMI undergoing primary PCI. METHODS AND RESULTS: We randomly assigned 450 STEMI patients to receive (1) preprocedure and postprocedure hydration of sodium bicarbonate (early hydration group), (2) postprocedure hydration of isotonic saline (late hydration group), or (3) no hydration (control group). The primary end point was the development of CI-AKI, defined as an increase in serum creatinine of >=25% or 0.5 mg/dL over the baseline value within 3 days after administration of the contrast medium. Moreover, we evaluated a possible relationship between the occurrence of CI-AKI and total hydration volume administered. There were no significant differences in baseline clinical, biochemical, and procedural characteristics in the 3 groups. Overall, CI-AKI occurred in 93 patients (20.6%): the incidence was significantly lower in the early hydration group (12%) with respect to both the late hydration group (22.7%) and the control group (27.3%) (P for trend=0.001). In hydrated patients (early and late hydration groups), lower infused volumes were associated with a significant increase in CI-AKI incidence, and the optimal cutoff point of hydration volume that best discriminates patients at higher risk was <=960 mL. CONCLUSIONS: Adequate intravenous volume expansion may prevent CI-AKI in patients undergoing primary PCI. A regimen of preprocedure and postprocedure hydration therapy with sodium bicarbonate appears to be more efficacious than postprocedure hydration only with isotonic saline. PMID- 21972404 TI - CYP2C19 but not PON1 genetic variants influence clopidogrel pharmacokinetics, pharmacodynamics, and clinical efficacy in post-myocardial infarction patients. AB - BACKGROUND: Reduced concentrations of clopidogrel active metabolite have been associated with diminished platelet inhibition and higher rates of adverse cardiovascular events. Paraoxonase-1 (PON1) has recently been proposed as a key enzyme for clopidogrel metabolic activation. We tested the effects of PON1 polymorphisms on clopidogrel pharmacokinetics and pharmacodynamics and the occurrence of cardiovascular outcomes in young post-myocardial infarction (MI) patients treated with clopidogrel. METHODS AND RESULTS: We genotyped PON1 (Q192R and L55M) and CYP2C19 variants in 106 patients enrolled in the PK/PD CLOVIS-2 trial. Patients were randomly exposed to a 300-mg or 900-mg clopidogrel loading dose in a crossover study design. Clopidogrel active metabolite isomer H4 (clopi H4) and platelet function testing were measured serially after loading dose. There was no significant association between PON1 Q192R or L55M and clopi-H4 formation or antiplatelet response to clopidogrel after either loading dose. Using multivariable linear regression analyses, the CYP2C19*2 allele was the only predictor of clopi-H4 generation and platelet response irrespective of the platelet function assay. CYP2C19 loss-of-function but not PON1 variants were significantly associated with increased risk of major cardiovascular events (death, MI, and urgent coronary revascularization) occurring during long-term clopidogrel exposure in 371 young post-MI patients (age <45 years) enrolled in the AFIJI cohort (CYP2C19 loss-of-function allele carrier versus noncarrier: hazard ratio, 2.26; 95% confidence interval, 1.15-4.41, P=0.02; PON1 QQ192 versus QR/RR192: hazard ratio, 1.03; 95% confidence interval, 0.50-2.11, P=0.93; PON1 LL55 versus LM/MM55: hazard ratio, 1.52; 95% confidence interval, 0.75-3.08, P=0.24). CONCLUSIONS: Our study does not confirm that PON1 Q192R or L55M can influence clopidogrel pharmacokinetics or pharmacodynamics in post-MI patients. PMID- 21972406 TI - Impact of free universal medical coverage on medical care and outcomes in low income patients hospitalized for acute myocardial infarction: an analysis from the FrenchNational Health Insurance system. AB - BACKGROUND: The type of medical coverage in patients with acute myocardial infarction (AMI) may affect their treatment and outcome. METHODS AND RESULTS: We used the reimbursement database from the French National Health Insurance to determine the impact of full medical coverage (Couverture Medicale Universelle Complementaire, CMUC), a free supplemental insurance for low-income earners <60 years of age, on treatment and outcomes of patients with AMI. The population comprised consecutive patients <60 years of age hospitalized for AMI from January to June 2006 in France. Of 4939 patients with AMI aged <60 years, 587 (12%) were on the CMUC. CMUC patients were younger, with more prior cardiovascular and comorbid conditions. CMUC and non-CMUC patients were admitted to the same types of institutions, including academic hospitals and private clinics. The use of cardiac catheterization and coronary interventions was similar (adjusted relative risk, 0.97; 95% confidence interval, 0.91-1.05; P=0.45). In-hospital mortality was also comparable (3.1% versus 2.8%, P=0.69). There was no difference in early use of secondary prevention medications after multivariate adjustment. At 30 months, survival and acute coronary syndrome-free survival were lower in CMUC patients (trend, not significant after adjustment). Long-term adherence to statin therapy was lower in CMUC patients (64% versus 77%; adjusted relative risk, 0.82; 95% confidence interval, 0.73-0.92). CONCLUSIONS: Free full coverage for socially deprived people levels inequalities in the acute and midterm treatment of AMI patients. However, full reimbursement per se is not sufficient to ensure optimal patient adherence to secondary prevention medications and may not be enough to prevent an excess of long-term events. PMID- 21972405 TI - Impact of incomplete revascularization on long-term mortality after coronary stenting. AB - BACKGROUND: The impact of incomplete revascularization (IR) on adverse outcomes after percutaneous coronary intervention remains inconclusive, and few studies have examined mortality during follow-ups longer than 5 years. The objective of this study is to test the hypothesis that IR is associated with higher risk of long-term (8-year) mortality after stenting for multivessel coronary disease. METHODS AND RESULTS: A total of 13 016 patients with multivessel disease who had undergone stenting procedures with bare metal stents in 1999 to 2000 were identified in the New York State's Percutaneous Coronary Intervention Reporting System. A logistic regression model was fit to predict the probability of achieving complete revascularization (CR) in these patients using baseline risk factors; then, the CR patients were matched to the IR patients with similar likelihoods of achieving CR. Each patient's vital status was followed through 2007 using the National Death Index, and the difference in long-term mortality between IR and CR was compared. It was found that CR was achieved in 29.2% (3803) of the patients. For the 3803 pair-matched patients, the respective 8-year survival rates were 80.8% and 78.5% for CR and IR (P=0.04), respectively. The risk of death was marginally significantly higher for IR (hazard ratio=1.12; 95% confidence interval, 1.01-1.26, P=0.04). The 95% bootstrap confidence interval for the hazard ratio was 0.98 to 1.32. CONCLUSIONS: IR may be associated with higher risk of long-term mortality after stenting with BMS in patients with multivessel disease. More prospective studies are needed to further test this association. PMID- 21972407 TI - Diabetes, glycemic control, and risk of tuberculosis: a population-based case control study. AB - OBJECTIVE: To examine the association between diabetes, glycemic control, and risk of tuberculosis (TB). RESEARCH DESIGN AND METHODS: We conducted a population based case-control study in Northern Denmark. Cases of active TB were all individuals with a first-time principal hospital diagnosis of TB between 1980 and 2008. Each case subject was matched with up to five population control subjects with similar age, sex, place and length of residence in Denmark, and country of emigration. We computed odds ratios (ORs) for a first-time TB diagnosis among people with and without diabetes using regression to control for other comorbidities, alcoholism, immunosuppressive medications, and socioeconomic markers. RESULTS: We identified 2,950 patients, including 156 diabetic individuals (5.3%), with active TB, and 14,274 population control subjects, of which 539 had diabetes (3.8%). The adjusted OR for active TB among subjects with diabetes was 1.18 (95% CI 0.96-1.45) compared with nondiabetic individuals. We found a similar risk increase from diabetes in the 843 (29%) TB case subjects who were immigrants; adjusted OR = 1.23 (95% CI 0.78-1.93). In a subset with laboratory data, diabetic individuals with an HbA(1c) <7.0, 7-7.9, and >=8.0% had ORs of 0.91 (0.51-1.63), 1.05 (0.41-2.66), and 1.19 (CI 0.61-2.30), respectively, compared with individuals without diabetes. CONCLUSIONS: In the low TB-burden country of Denmark, the TB risk increase associated with diabetes is substantially lower than previously suggested. We found no evidence for any association between TB and dysglycemia. PMID- 21972408 TI - Risk of breast cancer after onset of type 2 diabetes: evidence of detection bias in postmenopausal women. AB - OBJECTIVE: To examine the risk of breast cancer in pre- and postmenopausal women with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: This was a population based retrospective cohort study. Cox regression, stratified by pre- (<55 years) and postmenopausal (>=55 years) status, was used to estimate hazard ratios (HRs) for breast cancer, during earlier (0-3 months) and later (3 months to 10 years) time windows after diabetes index date. RESULTS: Compared with women without T2D, HRs for breast cancer were 0.95 (95% CI 0.48-1.86; P = 0.88) and 1.31 (0.92-1.86; P = 0.14) in pre- and postmenopausal women with T2D, respectively, in the early time window, and 0.92 (0.75-1.13; P = 0.45) and 1.00 (0.90-1.11; P = 0.93) in pre and postmenopausal women with T2D, respectively, in the later time window. CONCLUSIONS: We observed a trend toward an increased risk of breast cancer in postmenopausal women with T2D, but only in the time period immediately after diabetes index date. PMID- 21972409 TI - Reduced prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes in young children participating in longitudinal follow-up. AB - OBJECTIVE: Young children have an unacceptably high prevalence of diabetic ketoacidosis (DKA) at the clinical diagnosis of type 1 diabetes. The aim of this study was to determine whether knowledge of genetic risk and close follow-up for development of islet autoantibodies through participation in The Environmental Determinants of Diabetes in the Young (TEDDY) study results in lower prevalence of DKA at diabetes onset in children aged <2 and <5 years compared with population-based incidence studies and registries. RESEARCH DESIGN AND METHODS: Symptoms and laboratory data collected on TEDDY participants diagnosed with type 1 diabetes between 2004 and 2010 were compared with data collected during the similar periods from studies and registries in all TEDDY-participating countries (U.S., SEARCH for Diabetes in Youth Study; Sweden, Swediabkids; Finland, Finnish Pediatric Diabetes Register; and Germany, Diabetes Patienten Verlaufsdokumenation [DPV] Register). RESULTS: A total of 40 children younger than age 2 years and 79 children younger than age 5 years were diagnosed with type 1 diabetes in TEDDY as of December 2010. In children <2 years of age at onset, DKA prevalence in TEDDY participants was significantly lower than in all comparative registries (German DPV Register, P < 0.0001; Swediabkids, P = 0.02; SEARCH, P < 0.0001; Finnish Register, P < 0.0001). The prevalence of DKA in TEDDY children diagnosed at <5 years of age (13.1%) was significantly lower compared with SEARCH (36.4%) (P < 0.0001) and the German DPV Register (32.2%) (P < 0.0001) but not compared with Swediabkids or the Finnish Register. CONCLUSIONS: Participation in the TEDDY study is associated with reduced risk of DKA at diagnosis of type 1 diabetes in young children. PMID- 21972410 TI - Does glycemic control offer similar benefits among patients with diabetes in different regions of the world? Results from the ADVANCE trial. AB - OBJECTIVE: Participants in ADVANCE were drawn from many countries. We examined whether the effects of intensive glycemic control on major outcomes in ADVANCE differ between participants from Asia, established market economies (EMEs), and eastern Europe. RESEARCH DESIGN AND METHODS: ADVANCE was a clinical trial of 11,140 patients with type 2 diabetes, lasting a median of 5 years. Demographic and clinical characteristics were compared across regions using generalized linear and mixed models. Effects on outcomes of the gliclazide modified release based intensive glucose control regimen, targeting an HbA(lc) of <=6.5%, were compared across regions using Cox proportional hazards models. RESULTS: When differences in baseline variables were allowed for, the risks of primary outcomes (major macrovascular or microvascular disease) were highest in Asia (joint hazard ratio 1.33 [95% CI 1.17-1.50]), whereas macrovascular disease was more common (1.19 [1.00-1.42]) and microvascular disease less common (0.77 [0.62-0.94]) in eastern Europe than in EMEs. Risks of death and cardiovascular death were highest in eastern Europe, and the mean difference in glycosylated hemoglobin between the intensive and standard groups was lowest in EMEs. Despite these and other differences, the effects of intensive glycemic control were not significantly different (P >= 0.23) between regions for any outcome, including mortality, vascular end points, and severe hypoglycemic episodes. CONCLUSIONS: Irrespective of absolute risk, the effects of intensive glycemic control with the gliclazide MR-based regimen used in ADVANCE were similar across Asia, EMEs, and eastern Europe. This regimen can safely be recommended for patients with type 2 diabetes in all of these regions. PMID- 21972412 TI - Differential effects of adiposity on pharmacodynamics of basal insulins NPH, glargine, and detemir in type 2 diabetes mellitus. AB - OBJECTIVE: To assess the role of adiposity on the pharmacodynamics of basal insulins NPH, detemir, and glargine in type 2 diabetes mellitus (T2DM), as estimated by glucose infusion rate (GIR) and endogenous glucose production (EGP) rate in the euglycemic clamp. RESEARCH DESIGN AND METHODS: We examined the variables that best predicted GIR and EGP in 32-h clamp studies after treatment with subcutaneous injection of 0.4 units/kg NPH, detemir, and glargine in 18 T2DM subjects (crossover). RESULTS: A multiple regression analysis revealed that BMI best predicted GIR variation during the clamp. BMI was inversely correlated with GIR in all three insulin treatments, but was statistically significant in detemir treatment only. BMI correlated positively with residual suppression of EGP in detemir, but not with glargine and NPH treatments. CONCLUSIONS: Adiposity blunts the pharmacodynamics of all basal insulins in T2DM. However, as adiposity increases, the effect of detemir is lower versus NPH and glargine. PMID- 21972411 TI - The LiP (Lifestyle in Pregnancy) study: a randomized controlled trial of lifestyle intervention in 360 obese pregnant women. AB - OBJECTIVE: To study the effects of lifestyle intervention on gestational weight gain (GWG) and obstetric outcomes. RESEARCH DESIGN AND METHODS: The LiP (Lifestyle in Pregnancy) study was a randomized controlled trial in 360 obese women allocated in early pregnancy to lifestyle intervention or control. The intervention program included dietary guidance, free membership in fitness centers, physical training, and personal coaching. RESULTS: A total of 360 obese pregnant women were included, and 304 (84%) were followed up until delivery. The intervention group had a significantly lower median (range) GWG compared with the control group of 7.0 (4.7-10.6) vs. 8.6 kg (5.7-11.5; P = 0.01). The Institute of Medicine (IOM) recommendations on GWG were exceeded in 35.4% of women in the intervention group compared with 46.6% in the control group (P = 0.058). Overall, the obstetric outcomes between the two groups were not significantly different. CONCLUSIONS: Lifestyle intervention in pregnancy resulted in limited GWG in obese pregnant women. Overall obstetric outcomes were similar in the two groups. Lifestyle intervention resulted in a higher adherence to the IOM weight gain recommendations; however, a significant number of women still exceeded the upper threshold. PMID- 21972413 TI - Arterial stiffness is associated with incident albuminuria and decreased glomerular filtration rate in type 2 diabetic patients. AB - OBJECTIVE: To investigate the association between aortic stiffness and incident albuminuria and the decline in estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We investigated 461 Japanese type 2 diabetic patients, comprising 199 women and 262 men, with a mean age of 59 +/- 11 years. Patients were divided into two groups according to the median value of carotid-femoral pulse wave velocity (cf-PWV), which was used to evaluate aortic stiffness. The end point was defined as the transition from normo to microalbuminuria or micro- to macroalbuminuria. The Cox proportional hazard model was used to calculate the hazard ratio (HR) and 95% CI. The correlation between cf-PWV and rate of change in eGFR was also determined by linear regression analysis. RESULTS: The baseline mean (+/- SD) cf-PWV was 9.6 +/- 2.4 m/s. During a median follow-up period of 5.9 years (range 0.3-8.6), progression of albuminuria was observed in 85 patients. The 5-year cumulative incidence of the end point in patients with cf-PWV below and above the median was 8.5 and 19.4%, respectively (P = 0.002, log-rank test). cf-PWV was significantly associated with incident albuminuria (HR 1.23, 95% CI 1.13-1.33, P < 0.001) by multivariate Cox regression analysis. A significant association between cf-PWV and annual change in eGFR was also suggested by multiple linear regression analysis (standardized estimate -0.095, P = 0.031). CONCLUSIONS: Aortic stiffness is associated with incident albuminuria and the rate of decline in glomerular filtration rate in type 2 diabetic patients. PMID- 21972414 TI - Postpartum metabolic function in women delivering a macrosomic infant in the absence of gestational diabetes mellitus. AB - OBJECTIVE: Gestational diabetes mellitus (GDM) is associated with fetal macrosomia and maternal postpartum dysglycemia, insulin resistance, and beta-cell dysfunction. Indeed, in practice, a prior pregnancy that resulted in a large-for gestational-age (LGA) delivery is often considered presumptive evidence of GDM, whether or not it was diagnosed at the time. If this clinical assumption is correct, however, we would expect these women to exhibit postpartum metabolic dysfunction. Thus, to test this hypothesis, we assessed metabolic function during and after pregnancy in a cohort of women stratified according to the presence/absence of GDM and LGA delivery, respectively. RESEARCH DESIGN AND METHODS: A total of 562 women underwent metabolic characterization, including oral glucose tolerance test (OGTT), in late pregnancy and at 3 months' postpartum. The women were stratified into three groups: those with neither GDM nor LGA delivery (nonGDM, n = 364), those without GDM but with LGA delivery (nonGDM-LGA, n = 46), and those with GDM (n = 152). RESULTS: On logistic regression, GDM predicted postpartum glucose intolerance (OR 4.1 [95% CI 2.5 6.8]; P < 0.0001), whereas nonGDM-LGA did not (P = 0.65). At 3 months' postpartum, the mean adjusted levels of fasting glucose and area under the glucose curve on the OGTT were significantly higher in the GDM women compared with either nonGDM or nonGDM-LGA (all P < 0.05), with no differences between the latter two groups. In a similar manner, mean adjusted insulin sensitivity (Matsuda index) and beta-cell function (Insulin Secretion-Sensitivity Index-2) were lower in GDM women compared with either nonGDM or nonGDM-LGA (all P < 0.05), again with no differences between the latter two groups. CONCLUSIONS: Women with nonGDM-LGA do not exhibit postpartum metabolic dysfunction, arguing against the assumption of undiagnosed GDM in these patients. PMID- 21972415 TI - Furan fatty acid as an anti-inflammatory component from the green-lipped mussel Perna canaliculus. AB - A lipid extract of Perna canaliculus (New Zealand green-lipped mussel) has reportedly displayed anti-inflammatory effects in animal models and in human controlled studies. However, the anti-inflammatory lipid components have not been investigated in detail due to the instability of the lipid extract, which has made the identification of the distinct active components a formidable task. Considering the instability of the active component, we carefully fractionated a lipid extract of Perna canaliculus (Lyprinol) and detected furan fatty acids (F acids). These naturally but rarely detected fatty acids show potent radical scavenging ability and are essential constituents of plants and algae. Based on these data, it has been proposed that F-acids could be potential antioxidants, which may contribute to the protective properties of fish and fish oil diets against chronic inflammatory diseases. However, to date, in vivo data to support the hypothesis have not been obtained, presumably due to the limited availability of F-acids. To confirm the in vivo anti-inflammatory effect of F-acids in comparison with that of eicosapentaenoic acid (EPA), we developed a semisynthetic preparation and examined its anti-inflammatory activity in a rat model of adjuvant-induced arthritis. Indeed, the F-acid ethyl ester exhibited more potent anti-inflammatory activity than that of the EPA ethyl ester. We report on the in vivo activity of F-acids, confirming that the lipid extract of the green-lipped mussel includes an unstable fatty acid that is more effective than EPA. PMID- 21972416 TI - The transcription factors E2A and HEB act in concert to induce the expression of FOXO1 in the common lymphoid progenitor. AB - Recent studies have identified a number of transcriptional regulators, including E proteins, EBF1, FOXO1, and PAX5, that act together to orchestrate the B-cell fate. However, it still remains unclear as to how they are linked at the earliest stages of B-cell development. Here, we show that lymphocyte development in HEB ablated mice exhibits a partial developmental arrest, whereas B-cell development in E2A(+/-)HEB(-/-) mice is completely blocked at the LY6D(-) common lymphoid progenitor stage. We show that the transcription signatures of E2A- and HEB ablated common lymphoid progenitors significantly overlap. Notably, we found that Foxo1 expression was substantially reduced in the LY6D(-) HEB- and E2A-deficient cells. Finally, we show that E2A binds to enhancer elements across the FOXO1 locus to activate Foxo1 expression, linking E2A and FOXO1 directly in a common pathway. In summary, the data indicate that the earliest event in B-cell specification involves the induction of FOXO1 expression and requires the combined activities of E2A and HEB. PMID- 21972419 TI - Understanding how rapid response systems may improve safety for the acutely ill patient: learning from the frontline. AB - INTRODUCTION: Rapid response systems (RRSs) have been introduced to facilitate effective 'rescue' of seriously ill patients on hospital wards. While research has demonstrated some benefit, uncertainty remains regarding impact on patient outcomes. Little is known about the relationship between social contexts and the application of the RRS. DESIGN: This comparative case study of the RRS within the medical services of two UK hospitals used ethnographic methods over a 12-month period in 2009, including observation (ward work and shadowing medical staff = 150 h), interviews with doctors, ward and critical care nurses, healthcare assistants, safety leads and managers (n=35), documentary review and analysis of routine data. Data were analysed using NVivo software. RESULTS: The RRS reduced variability in recording, recognition and response behaviour. The RRS formalised understandings of deterioration and provided a mandate for escalating care across professional and hierarchical boundaries. However, markers of deterioration not assimilated into risk scores were marginalised and it was harder for staff to escalate care without the 'objective evidence' provided by the score. Contextual features (eg, leadership, organisational culture and training) shaped implementation, utilisation and impact of the RRS. Reporting and feedback of audit data enabled learning about 'selected' escalation work on the wards. Difficulties with referral upwards and across medical boundaries were reported by junior medical staff. CONCLUSION: Locating a RRS within a pathway of care for the acutely ill patient illustrates the role of these safety strategies within the social organisation of clinical work. There is a need to broaden the focus of inquiry from detection and initiation of escalation (where the strategies are principally directed) towards team response behaviour and towards those medical response practices which to date have escaped scrutiny and monitoring. PMID- 21972420 TI - Work participation and work transition in patients with systemic sclerosis: a cross-sectional study. AB - OBJECTIVES: To describe work participation and work transition due to health in patients with SSc. Associations are assessed between having made a work transition or not and factors possibly influencing that transition. METHODS: This study included patients visiting the Scleroderma Clinic of the Ghent University Hospital, who regularly undergo an extensive evaluation. For this study, a questionnaire was used to collect work participation and work transition data. RESULTS: Eighty-four patients in the adult working-age population were included. Thirty-eight (45%) out of 84 patients participated in the labour force. Forty-six (55%) out of 84 were not engaged in a paid job; in 34 (74%) out of 46 patients this was attributed to health issues. Seventy-six (90%) out of 84 patients made a work transition. Forty-seven (62%) out of 76 made that transition due to health reasons. The group that made a health-related work transition (47/84, 56%) was compared with the remaining group (37/84, 44%) that made no work transition or a work transition for reasons other than health. There was a significant difference in educational level, skin score, lung disease severity, disease activity, disease duration, scleroderma Health Assessment Questionnaire (sHAQ), visual analogue scale (VAS) for RP, VAS for intestinal disease, VAS for overall disease, VAS for pain, Medical Outcomes Study short form 36 (SF-36), work statute and willingness to participate in training. The multivariate analysis retained sHAQ, SF-36 and disease duration as associating variables. CONCLUSIONS: Work participation is limited in patients with SSc and a majority make a work transition because of health problems. Demographic, disease- and work-related variables, as well as willingness to participate in training are associated with (the occurrence of) work transition. PMID- 21972418 TI - Impaired phosphorylation of Na(+)-K(+)-2Cl(-) cotransporter by oxidative stress responsive kinase-1 deficiency manifests hypotension and Bartter-like syndrome. AB - Na(+)-K(+)-2Cl(-) cotransporters (NKCCs), including NKCC1 and renal-specific NKCC2, and the Na(+)-Cl(-) cotransporter (NCC) play pivotal roles in the regulation of blood pressure (BP) and renal NaCl reabsorption. Oxidative stress responsive kinase-1 (OSR1) is a known upstream regulator of N(K)CCs. We generated and analyzed global and kidney tubule-specific (KSP) OSR1 KO mice to elucidate the physiological role of OSR1 in vivo, particularly on BP and kidney function. Although global OSR1(-/-) mice were embryonically lethal, OSR1(+/-) mice had low BP associated with reduced phosphorylated (p) STE20 (sterile 20)/SPS1-related proline/alanine-rich kinase (SPAK) and p-NKCC1 abundance in aortic tissue and attenuated p-NKCC2 abundance with increased total and p-NCC expression in the kidney. KSP-OSR1(-/-) mice had normal BP and hypercalciuria and maintained significant hypokalemia on a low-K(+) diet. KSP-OSR1(-/-) mice exhibited impaired Na(+) reabsorption in the thick ascending loop on a low-Na(+) diet accompanied by remarkably decreased expression of p-NKCC2 and a blunted response to furosemide, an NKCC2 inhibitor. The expression of total SPAK and p-SPAK was significantly increased in parallel to that of total NCC and p-NCC despite unchanged total NKCC2 expression. These results suggest that, globally, OSR1 is involved in the regulation of BP and renal tubular Na(+) reabsorption mainly via the activation of NKCC1 and NKCC2. In the kidneys, NKCC2 but not NCC is the main target of OSR1 and the reduced p-NKCC2 in KSP-OSR1(-/-) mice may lead to a Bartter-like syndrome. PMID- 21972421 TI - Assessment of active inflammation in juvenile dermatomyositis: a novel magnetic resonance imaging-based scoring system. AB - OBJECTIVE: To assess the reproducibility of a novel scoring system that we have developed for the objective assessment of acute inflammatory change in JDM. This system defines markers of inflammatory change in four muscle groups and the surrounding soft tissues. METHODS: Forty-eight children (33 girls) underwent retrospective assessment of their MRI studies by two musculoskeletal paediatric radiologists for the presence of disease activity. Each observer performed the readings on two separate occasions. The degree of concordance between the two observers and between the two readings was assessed using kappa analysis. The reproducibility of the total score was determined using Bland-Altman analysis. RESULTS: There was fair to moderate agreement between the two observers for all the examined disease activity markers in all muscle groups. There was good intra observer agreement between the two readings. There was no difference according to the side evaluated. The mean total score (out of 20) for Observer 1 was 7.9 and for Observer 2 was 7.5 (mean difference -0.4, 95% limits of agreement -6.8 to 6.0), while the mean total scores for Observer 1 were 9.0 for the first reading and 7.9 for the second reading (mean difference 1.0, 95% limits of agreement -2.6 to 4.6). CONCLUSION: Markers of inflammatory change in JDM can be observed on MRI in a reliable fashion and have been used to make a reliable and objective scoring system. The accuracy of the proposed scoring system is acceptable for the single reader, although there is more variability between two different individuals. PMID- 21972422 TI - Down-regulated HS6ST2 in osteoarthritis and Kashin-Beck disease inhibits cell viability and influences expression of the genes relevant to aggrecan metabolism of human chondrocytes. AB - OBJECTIVE: Primary OA and Kashin-Beck disease (KBD) show similar pathological changes in articular cartilage. The objective was to screen differentially expressed genes between OA and normal cartilage, confirm the candidate gene expression among OA, KBD and normal cartilage, and then clarify its role in vitro. METHODS: Differentially expressed genes in OA cartilage were screened by suppression subtractive hybridization (SSH) and verified by real-time quantitative PCR (Q-PCR) analysis. Heparan sulphate 6-O-sulphotransferase 2 (HS6ST2) expression was identified by Q-PCR and immunohistochemistry. After suppressing HS6ST2 by RNA interference in C28/I2 human chondrocyte line, the effects were analysed through determining the cell viability by 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), the aggrecan contents by toluidine blue staining and the mRNA expression levels of SRY-type high mobility group box 9 (SOX9), AGC1, MMP3, a disintegrin and metalloproteinase domain with thrombospondin motifs 4 (ADAMTS4) and ADAMTS5 by Q-PCR. RESULTS: HS6ST2 in the reverse subtraction library was identified as a down-regulated gene in OA and KBD at both mRNA and protein levels. The percentage of safranion O staining area was correlated positively with the percentage of HS6ST2-positive chondrocytes in OA and KBD cartilage. After HS6ST2-specific short interfering RNA (siRNA) transfection to C28/I2 cells, the cell viability was inhibited significantly, and the mRNA expression levels of SOX9 and AGC1 were reduced markedly, while MMP3 expression was increased significantly. CONCLUSION; HS6ST2 down-regulation was identified in both OA and KBD cartilage. The findings first suggest that HS6ST2 may participate in the pathogenesis of OA and KBD by influencing aggrecan metabolism. PMID- 21972423 TI - Increased MMP-2 in healthy postmenopausal women. AB - BACKGROUND: Matrix metalloproteases 2 (MMP-2) and 9 (MMP-9) are involved in the atherosclerosis process. The objective of the study was to evaluate MMP-2 and MMP 9 activities and other circulating inflammatory factors in healthy postmenopausal women (PMW) as a model of subclinical atherosclerosis. METHODS: Twenty-three PMW and 13 premenopausal women (PreMW) were selected following established criteria. The main measurements in plasma samples were: lipid-lipoprotein profile, high sensitivity C-reactive protein (hs-CRP) (immunoturbidimetry), soluble vascular cellular adhesion molecules (sVCAM-1) enzyme-linked immunosorbent assay and MMP activity by zymography. RESULTS: The relative areas of MMP-2 were increased in PMW: 1.1 (0.1) versus 0.6 (0.05), P < 0.02. MMP-9 was only detected in three PMW and one PreMW. MMP-2 correlated with HDL-cholesterol (r = -0.51), triglycerides (r = 0.67), apolipoprotein B (r = 0.47), hs-CRP (r = 0.42), homeostasis model assessment (r = 0.53) and waist circumference (r = 0.40), at least P < 0.02. sVCAM-1 showed no difference between groups: 28.7 (5.5) versus 35.5 (20) ng/mL, but correlated with MMP-2 and hs-CRP (r = 0.46 and r = 0.48 respectively, P < 0.05). CONCLUSIONS: In postmenopause, the increase in MMP-2 reflects the systemic specific inflammatory process that accompanies atherogenesis. PMID- 21972424 TI - Atorvastatin therapy decreases androstenedione and dehydroepiandrosterone sulphate concentrations in patients with polycystic ovary syndrome: randomized controlled study. AB - BACKGROUND: Hyperandrogenaemia in polycystic ovary syndrome (PCOS) represents a composite of raised serum concentrations of testosterone, androstenedione, dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS). In patients with PCOS, testosterone and androstenedione are primarily derived from the ovaries and DHEAS is a metabolite predominantly from the adrenals. It has been shown that atorvastatin reduces testosterone concentrations in patients with PCOS. The objective was to study the effect of atorvastatin on serum androstenedione and DHEAS concentrations in patients with PCOS. METHODS: A randomized, double-blind, placebo-controlled study was performed. Forty medication-naive patients with PCOs were randomized to either atorvastatin 20mg daily or placebo for three months. Subsequently, a three-month extension study for all patients was undertaken with metformin 1500 mg daily. The main outcome measures were change in androstenedione and DHEAS concentrations. RESULTS: The mean (SD) baseline androstenedione (5.7 [0.8] versus 5.6 [1.3] nmol/L; P = 0.69) and DHEAS (7.1 [1.0] versus 7.2 [1.2] MUmol/L; P = 0.72) concentrations were comparable between two groups. There was a significant reduction of androstenedione (5.7 [0.8] versus 4.7 [0.7] nmol/L; P = 0.03) and DHEAS (7.1 [1.0] versus 6.0 [0.9] MUmol/L; P = 0.02) with three months of atorvastatin while there were no significant changes with placebo. Three months' treatment with metformin maintained the reduction of androstenedione and DHEAS concentrations with atorvastatin compared with baseline. There were no changes in either DHEAS or androstenedione concentrations in the initial placebo group after 12 weeks of metformin. CONCLUSIONS: Twelve weeks of atorvastatin significantly reduced both DHEAS and androstenedione contributing to the total reduction of androgen concentrations and indicating that the reduction of the hyperandrogenaemia could be partly due to the action of atorvastatin at both the ovary and the adrenal gland in PCOS. PMID- 21972426 TI - Taking a different perspective: mindset influences neural regions that represent value and choice. AB - Most choices are complex and can be considered from a number of different perspectives. For example, someone choosing a snack may have taste, health, cost or any number of factors at the forefront of their mind. Although previous research has examined neural systems related to value and choice, very little is known about how mindset influences these systems. In the current study, participants were primed with Health or Taste while they made decisions about snack foods. Some neural regions showed consistent associations with value and choice across Health or Taste mindsets. Regardless of mindset, medial orbitofrontal cortex (MOFC) tracked value in terms of taste, regions in left lateral prefrontal cortex (LPFC) tracked value in terms of health, and MOFC and dorsal anterior cingulate were associated with choice. However, activity in other neural regions was modulated by the mindset manipulation. When primed with Taste, rostral anterior cingulate tracked value in terms of taste whereas left amygdala and left putamen were associated with choice. When primed with Health, right LPFC and posterior MOFC tracked value in terms of health. The findings contribute to the neural research on decision-making by demonstrating that changing perspectives can modulate value- and choice-related neural activity. PMID- 21972427 TI - Abstracts of the 36th European Congress of Cytology. Istanbul, Turkey. September 22-25, 2011. PMID- 21972428 TI - Abstracts of the College of Emergency Medicine Autumn Conference. Gateshead, United Kingdom. September 21-23, 2011. PMID- 21972425 TI - Storm in a coffee cup: caffeine modifies brain activation to social signals of threat. AB - Caffeine, an adenosine A1 and A(2A) receptor antagonist, is the most popular psychostimulant drug in the world, but it is also anxiogenic. The neural correlates of caffeine-induced anxiety are currently unknown. This study investigated the effects of caffeine on brain regions implicated in social threat processing and anxiety. Participants were 14 healthy male non/infrequent caffeine consumers. In a double-blind placebo-controlled crossover design, they underwent blood oxygenation level-dependent functional magnetic resonance imaging (fMRI) while performing an emotional face processing task 1 h after receiving caffeine (250 mg) or placebo in two fMRI sessions (counterbalanced, 1-week washout). They rated anxiety and mental alertness, and their blood pressure was measured, before and 2 h after treatment. Results showed that caffeine induced threat-related (angry/fearful faces > happy faces) midbrain-periaqueductal gray activation and abolished threat-related medial prefrontal cortex wall activation. Effects of caffeine on extent of threat-related amygdala activation correlated negatively with level of dietary caffeine intake. In concurrence with these changes in threat-related brain activation, caffeine increased self-rated anxiety and diastolic blood pressure. Caffeine did not affect primary visual cortex activation. These results are the first to demonstrate potential neural correlates of the anxiogenic effect of caffeine, and they implicate the amygdala as a key site for caffeine tolerance. PMID- 21972429 TI - Treatment of type IV thoracoabdominal aneurysms--open, hybrid technique with debranching or fenestrated stent-graft repair. PMID- 21972430 TI - Abstracts of the AABB Annual Meeting and CTTXPO. San Diego, California, USA. October 22-25, 2011. PMID- 21972431 TI - Cutting feedback in Bayesian regression adjustment for the propensity score. AB - McCandless, Gustafson and Austin (2009) describe a Bayesian approach to regression adjustment for the propensity score to reduce confounding. A unique property of the method is that the treatment and outcome models are combined via Bayes theorem. However, this estimation procedure can be problematic if the outcome model is misspecified. We observe feedback that can bias propensity score estimates. Building on new innovation in Bayesian computation, we propose a technique for cutting feedback in a Bayesian propensity analysis. We use the posterior distribution of the propensity scores as an input in the regression model for the outcome. The method is approximately Bayesian in the sense that it does not use the full likelihood for estimation. Nonetheless, it severs feedback between the treatment and outcome giving propensity score estimates that are free from bias but modeled with uncertainty. We illustrate the method in a matched cohort study investigating the effect of statins on primary stroke prevention. PMID- 21972432 TI - Bayesian inference for partially identified models. AB - Identification can be a major issue in causal modeling contexts, and in contexts where observational studies have various limitations. Partially identified models can arise, whereby the identification region for a target parameter--the set of values consistent with the law of the observable data--is strictly contained in the set of a priori plausible values, but strictly contains the single true value. The first part of this paper reviews the use of Bayesian inference in partially identified models, and describes the large-sample limit of the posterior distribution over the target parameter. This limiting distribution will have the identification region as its support. The second part of the paper focuses on the informativeness of the shape of the limiting distribution. This provides a point of departure with non-Bayesian approaches, since they focus on inferring the identification region without attempting to speak to relative plausibilities of values inside the identification region. The utility of the shape is investigated in several partially identified models. PMID- 21972433 TI - When to start treatment? A systematic approach to the comparison of dynamic regimes using observational data. AB - Dynamic treatment regimes are the type of regime most commonly used in clinical practice. For example, physicians may initiate combined antiretroviral therapy the first time an individual's recorded CD4 cell count drops below either 500 cells/mm3 or 350 cells/mm3. This paper describes an approach for using observational data to emulate randomized clinical trials that compare dynamic regimes of the form "initiate treatment within a certain time period of some time varying covariate first crossing a particular threshold." We applied this method to data from the French Hospital database on HIV (FHDH-ANRS CO4), an observational study of HIV-infected patients, in order to compare dynamic regimes of the form "initiate treatment within m months after the recorded CD4 cell count first drops below x cells/mm3" where x takes values from 200 to 500 in increments of 10 and m takes values 0 or 3. We describe the method in the context of this example and discuss some complications that arise in emulating a randomized experiment using observational data. PMID- 21972434 TI - [Multivariate analysis on virologic breakthrough in HBeAg positive patients treated with lamivudine]. PMID- 21972435 TI - [Expressions and significance of Smadl/5 and p38 MAPK in regenerated liver tissue of rats]. PMID- 21972436 TI - [Expressions and significance of CD133 and CD90 in hepato cellular carcinoma]. PMID- 21972437 TI - [Study on the patients with liver transplantation associated hyperglycemia]. PMID- 21972438 TI - [Effect of indoleamine 2,3-dioxygenase on the biological behaviour of HepG2 cells]. PMID- 21972439 TI - [Chronic hepatitis C combined with Sheehan's syndrome: a case report]. PMID- 21972440 TI - [A case with poly-bone pain, decrease of bone density and in crease of serum creatinine related to adefovir dipivoxil treatment in a chronic hepatitis B patient]. PMID- 21972441 TI - [A giant ectopic liver in right mediastinum: a case report]. PMID- 21972442 TI - [Liver malignant lymphoma with hypercalcaemia: a case report]. PMID- 21972443 TI - [A report from the second symposium on the hots and difficult points during antiviral therapy for chronic hepatitis B]. PMID- 21972444 TI - [Introduction and comments on EASL clinical practice guidelines: management of hepatitis C virus infection]. PMID- 21972445 TI - [The joint pathway of metabolism and inflammation in nonalcoholic fatty liver disease]. PMID- 21972446 TI - [Research advances on chimeric mice with humanized liver]. PMID- 21972447 TI - AcrySof IQ toric IOL implantation combined with limbal relaxing incision during cataract surgery for eyes with astigmatism >2.50 D. AB - PURPOSE: To evaluate the effectiveness of toric intraocular lens (IOL) implantation combined with limbal relaxing incision (LRI) for patients with high amplitude astigmatism. METHODS: This single-center, prospective study evaluated 22 eyes of 19 patients with cataract and >2.50 diopters (D) astigmatism that underwent bimanual micro-phacoemulsification cataract surgery and toric IOL implantation combined with LRI. Pre- and 6-month postoperative uncorrected and corrected distance visual acuity (UDVA and CDVA, respectively), subjective cylindrical error, refractive cylindrical error, keratometric cylinder, and corneal topography were compared. Vector analysis of change in keratometric cylinder was compared pre- and postoperatively. RESULTS: Pre- and postoperative logMAR UDVA were 0.82 +/- 0.46 and 0.13 +/- 0.19, respectively; pre- and postoperative logMAR CDVA were 0.35 +/- 0.39 and 0.005 +/- 0.13, respectively. Mean postoperative refractive cylindrical error was 1.07 +/- 0.60 D. Although predicted residual astigmatism after implantation of the toric IOL was 1.42 +/- 0.76 D, pre- and postoperative subjective cylindrical error and keratometric cylinder changed from 3.90 D to 0.94 D and from 3.46 D to 1.80 D, respectively. CONCLUSIONS: Our results show that the combined surgery of toric IOL implantation and LRI is effective in patients with high-amplitude astigmatism >2.50 D. PMID- 21972448 TI - The use of botulinum toxin for pediatric cricopharyngeal achalasia. AB - OBJECTIVES: Cricopharyngeal achalasia is an uncommon cause of feeding difficulties in the pediatric population, and is especially rare in infants. Traditional management options include dilation or open cricopharyngeal myotomy. The use of botulinum toxin has been preliminarily reported for cricopharyngeal achalasia in children as a modality for diagnosis and management. This study describes the use of botulinum toxin as a definitive treatment for pediatric cricopharyngeal achalasia. METHODS: A retrospective analysis was performed of three patients who were diagnosed with cricopharyngeal achalasia and underwent botulinum toxin injections to the cricopharyngeus muscle. The charts were reviewed for etiology, botulinum toxin dosage delivered, length of follow-up, postoperative need for nasogastric tube placement, and swallow studies. RESULTS: A total of 7 botulinum toxin injections into the cricopharyngeus muscle were performed in three infants with primary cricopharyngeal achalasia between April 2006 and February 2011. Mean dosage was 23.4 units per session (range: 10-44 units), or 3.1 U/kg (range: 1.4-5.3 U/kg). Mean interval period between injections was 3.3 months (range: 2.7-4.0 months). Mean follow-up period was 22.1 months (range: 3.4-44.5 months). One patient required hospital readmission after injection for presumed aspiration but recovered without need for surgical intervention. No long-term complications were noted post-operatively. All patients improved clinically and ultimately had their nasogastric feeding tubes removed. CONCLUSIONS: Botulinum toxin appears to be a safe and effective option in the management of primary cricopharyngeal achalasia in children, and may prevent the need for myotomy. PMID- 21972449 TI - Abstracts of IV Scandinavian COPD Research Symposium. Holmenkollen, Oslo, Norway. November 19-20, 2010. PMID- 21972450 TI - Visual and IOP outcomes after PRK in pigment dispersion syndrome. AB - PURPOSE: To report the results of photorefractive keratectomy (PRK) in patients with pigment dispersion syndrome. METHODS: The pre- and postoperative records of patients with pigment dispersion syndrome who underwent PRK between January 2002 and March 2009 were reviewed. Data for analysis included gender, age, ablation depth, surgical complications, manifest refraction spherical equivalent, uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), intraocular pressure (IOP), central corneal thickness (CCT), cup-to-disc (c/d) ratio, and postoperative complications. RESULTS: Thirty-seven eyes of 19 patients (17 men and 2 women) with a mean age of 37.5 +/- 6.9 years were included for review. At final follow-up, mean 404.1+/-119.5 days postoperative, UDVA was 20/15 or better in 67.6%, 20/20 or better in 91.9%, and 20/25 or better in 100% of eyes; 94.6% of eyes were within 0.50 diopters (D) and 100% were within 1.00 D of emmetropia. Corrected distance visual acuity was unchanged from preoperative in 73% and improved by one line in 27% of eyes. No eye lost 1 or more lines of CDVA. When corrected for change in CCT and curvature, mean postoperative IOP was elevated from baseline (16.7 +/- 3.8 mmHg) at 1 month (18.1 +/- 4.9 mmHg, P =.044) but unchanged at any other time postoperatively. Two (11%) of 19 patients were steroid responders, requiring a single topical agent until completing the course of steroids. No significant change was noted in mean c/d ratio from baseline (0.35+/-0.12) to final postoperative (0.35 +/- 0.13, P = .99). CONCLUSIONS: Although PRK in patients with pigment dispersion syndrome resulted in excellent UDVA, retention of CDVA, and low incidence of adverse effects 1 to 2 years after surgery, long-term safety and efficacy outcomes of PRK in this cohort remain speculative PMID- 21972451 TI - Abstracts of the Annual Congress of the European Association of Nuclear Medicine. October 15-19, 2011. Birmingham, United Kingdom. PMID- 21972452 TI - I never expected to have such an interesting career, meet so many stimulating people and see so many exotic places. PMID- 21972453 TI - [Fluid resuscitation can be harmful in resource-poor countries]. PMID- 21972454 TI - Abstracts of the 8th Annual Controversies in Dialysis Access. Washington, D.C., USA. October 10-11, 2011. PMID- 21972455 TI - [Abstracts of German Pain Congress 2011. October 5-8, 2011. Mannheim, Germany]. PMID- 21972456 TI - [Assessment of the interest of using confirmatory test in ELISA with use of high concentration of heparin-induced thrombocytopenia]. PMID- 21972457 TI - Supplemental fluoride use for moderate and high caries risk adults: a systematic review. AB - OBJECTIVES: Multiple systematic reviews have evaluated fluorides for caries prevention in children, but a need to review the literature regarding supplemental fluoride use in adults still remains. The purpose of this systematic review is to evaluate the research regarding professional and/or supplemental self-applied fluoride for preventing and remineralizing caries in moderate and high caries risk adults. METHODS: Utilizing multiple databases, a comprehensive search was undertaken in both foreign and English languages. Studies included were randomized control trials (RCT) or clinical trials conducted in moderate or high caries risk adult populations, evaluating self- or professionally applied fluoride with the outcomes of caries reduction/remineralization. Studies were excluded if they were in situ, in vitro, split mouth design, or with unclear outcomes specific to fluorides. A quality evaluation of the studies used a checklist of critical domains and elements for an RCT. RESULTS: Seventeen studies were included in the systematic review. Findings were categorized into the following groups: sodium fluoride (NaF) and amine/potassium fluoride mouthrinses of varying strengths, NaF gels and pastes, NaF varnish, and stannous fluoride. Quality evaluation scores varied from 50.2 percent to 88.9 percent. CONCLUSIONS: The strongest studies demonstrated the following modalities as moderately effective in higher caries risk adults: low strength NaF rinses [risk reduction (RRR) for carious lesions: 50-148 percent]; 1.1 percent NaF pastes/gels (RRR for root lesion remineralization: 35-122 percent); fluoride varnishes [RRR for RC remineralization: 63 percent; RRR for decrease in decayed, missing, and filled surfaces: 50 percent]. Evidence regarding 1.1 percent NaF and 5 percent NaF varnishes related primarily to root caries and older adults. PMID- 21972458 TI - Development and validation of a measure of pediatric oral health-related quality of life: the POQL. AB - OBJECTIVE: To develop a brief measure of oral health-related quality of life (OHQL) in children and demonstrate its reliability and validity in a diverse population. METHODS: We administered the initial 20-item Pediatric Oral Health Related Quality of Life (POQL) to children (Child Self-Report) and parents (Parent Report on Child) from diverse populations in both school-based and clinic based settings. Clinical oral health status was measured on a subset of children. We used factor analysis to determine the underlying scales and then reduced the measure to 10 items based on several considerations. Multitrait analysis on the resulting 10-item POQL was used to reaffirm the discrimination of scales and assess the measure's internal consistency and interscale correlations. We established discriminant and convergent validity with clinical status, perceived oral health and responses on the PedsQL, and determined sensitivity to change with children undergoing ECC surgical repair. RESULTS: Factor analysis returned a four-scale solution for the initial items--Physical Functioning, Role Functioning, Social Functioning, and Emotional Functioning. The reduced items represented the same four scales--two each on Physical and Role and three each on Social and Emotional. Good reliability and validity were shown for the POQL as a whole and for each of the scales. CONCLUSIONS: The POQL is a valid and reliable measure of OHQL for use in preschool and school-aged children, with high utility for both clinical assessments and large-scale population studies. PMID- 21972459 TI - Oral health-related quality of life and perceived dental needs in the United States. AB - OBJECTIVES: The purpose of this study is to investigate the oral health-related quality of life (OHRQOL) in the US population by sociodemographic factors, perception of dental needs, reported dental visits, and saliva indicators. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004 were used. NHANES measured OHRQOL by a modified version of the Oral Health Impact Profile. RESULTS: The study had 6,183 subjects who averaged an OHRQOL score of 2.8 points. About 40% had painful aching in the mouth during the last year on at least one occasion. Perceived need to relieve dental pain was the strongest risk factor for poor OHRQOL (resulting in a higher score by 5.2 points), followed by perceived need for a denture or feeling of dry mouth (each resulting in a higher score by about 2 points). CONCLUSIONS: OHRQOL is the poorest among those with perceived dental needs especially those with the perceived need to relieve dental pain. PMID- 21972460 TI - The influence of comorbidity and other health measures on dental and medical care use among Medicare beneficiaries 2002. AB - OBJECTIVE: To assess the impact of comorbidity and other health measures on the use of dental and medical care services among the community-based Medicare population with data from the 2002 Medicare Current Beneficiary Survey. METHODS: A comorbidity index is the main independent variable of our study. It includes oral cancer as a comorbidity condition and was developed from Medicare claims data. The two outcome variables indicate whether a beneficiary had a dental visit during the year and whether the beneficiary had an inpatient hospital stay during the year. Logistic regressions estimated the relationship between the outcome variables and comorbidity after controlling for other explanatory variables. RESULTS: High scores on the comorbidity index, high numbers of self-reported physical limitations, and fair or poor self-reported health status were correlated with higher hospital use and lower dental care utilization. Similar results were found for types of medical care including medical provider visits, outpatient care, and prescription drugs. A multiple imputation technique was used for the approximate 20 percent of the sample with missing claims, but the resulting comorbidity index performed no differently than the index constructed without imputation. CONCLUSIONS: Comorbidities and other health status measures are theorized to play either a predisposing or need role in determining health care utilization. The study's findings confirm the dominant role of these measures as predisposing factors limiting access to dental care for Medicare beneficiaries and as need factors producing higher levels of inpatient hospital and other medical care for Medicare beneficiaries. PMID- 21972461 TI - A typology of models for expanding access to oral health care for people living with HIV/AIDS. AB - OBJECTIVES: This article describes a typology of program models for expanding access to dental services for people living with HIV/AIDS (PLWHA). These programs serve communities with limited access and high unmet need for oral health care, such as rural areas, low-income and racial/ethnic minorities. METHODS: Interviews and site visits with dental and program directors were conducted at participating sites, including AIDS service organizations, community health centers, and university-affiliated medical centers or hospitals. RESULTS: Despite the differences across organizational structure, similar models and approaches were developed to engage and retain PLWHA in dental care. These approaches included: using mobile dental units; expanding the type and availability of previous dental services provided; providing training opportunities for dental residents and hygienists; establishing linkages with medical providers; providing transportation and other ancillary services; using dental case managers and peer navigators to coordinate care; and patient education. CONCLUSIONS: This typology can assist program planners, medical and dental care providers with service delivery strategies for addressing the unmet need for oral health care in their area. PMID- 21972462 TI - Identifying the "vulnerables" in biomedical research: the vox populis from the Tuskegee Legacy Project. AB - OBJECTIVES: This report presents, for the first time, findings on the vox populis as to who constitutes the "vulnerables in biomedical research" METHODS: The 3 City Tuskegee Legacy Project (TLP) study used the TLP questionnaire as administered via random-digit-dial telephone interviews to 1162 adult Black people, non-Hispanic White people, and two Puerto Rican (PR) Hispanic groups: Mainland United States and San Juan (SJ) in three cities. The classification schema was based upon respondents' answers to an open-ended question asking which groups of people were the most vulnerable when participating in biomedical research. RESULTS: Subjects provided 749 valid open-ended responses, which were grouped into 29 direct response categories, leading to a four-tier classification schema for vulnerability traits. Tier 1, the summary tier, had five vulnerability categories: (1) Race/ ethnicity; (2) Age; (3) SES; (4) Health; and, (5) Gender. Black people and Mainland United States PR Hispanics most frequently identified Race/Ethnicity as a vulnerability trait (42.1 percent of Black people and 42.6 percent of Mainland United States. PR Hispanics versus 15.4 percent of White people and 16.7 percent of SJ R Hispanics) (P < 0.007), while White people and SJ PR Hispanics most frequently identified Age (48.3 percent and 29.2 percent) as a vulnerability trait. CONCLUSIONS: The response patterns on "who was vulnerable" were similar for the two minority groups (Black people and Mainland US PR Hispanics), and notably different from the response patterns of the two majority groups (White people and SJ PR Hispanics). Further, the vox populis definition of vulnerables differed from the current official definitions as used by the U.S. federal government. PMID- 21972463 TI - Amoxicillin use during early childhood and fluorosis of later developing tooth zones. AB - OBJECTIVES: Amoxicillin use has been reported to be associated with developmental defects on enamel surfaces. This analysis assessed the association between amoxicillin use and fluorosis on late-erupting permanent teeth. METHODS: As part of the Iowa Fluoride Study, subjects were followed from birth to 32 months with questionnaires every 3-4 months to gather information on fluoride intake and amoxicillin use (n = 357 subjects for this analysis). Permanent tooth fluorosis on late-erupting zones was assessed by three trained dentists using the fluorosis risk index (FRI) at approximately age 13. A case was defined as fluorosis if a subject had at least two FRI classification II zone scores of 2 or 3. Chi-square tests and logistic regression were used, and relative risks (RRs) and odds ratios (ORs) were calculated. RESULTS: There were 113 cases and 244 controls. In bivariate analyses, amoxicillin use from 20 to 24 months significantly increased the risk of fluorosis on FRI classification II zones [44.2 percent versus 30.4 percent, [RR = 1.45, 95 percent confidence interval (CI) 1.05-2.04], but other individual time periods did not. Multivariable logistic regression confirmed the increased risk of fluorosis for amoxicillin use from 20 to 24 months (OR = 2.92, 95 percent CI = 1.34-6.40), after controlling for otitis media, breast-feeding, and fluoride intake. CONCLUSIONS: Amoxicillin use during early childhood could be a risk factor in the etiology of fluorosis on late-erupting permanent tooth zones, but further research is needed. PMID- 21972464 TI - Geographic distribution of dentists in Japan: 1980-2000. AB - OBJECTIVE: In the late 1950s and 1960s, Japan recognized that it had a shortage of dentists and that they were unevenly distributed. To solve these problems, four national and eight private dental schools were established, leading to a significant increase in the number of dental students in the 1970s and 1980s. The purpose of this study was to investigate the effects of this increased supply on the geographic distribution of dentists in Japan. METHOD: We determined the number of dentists and the population in each of Japan's 3252 municipalities. The ratio of the number of dentists to the population of an area was assessed using Gini coefficients calculated from Lorenz curves. RESULTS: From 1980 to 2000, the average number of dentists per 100,000 persons in Japan increased from 44 to 70. The Lorenz curve plotted for 1980-1990 appeared as a nearly diagonal line, with the Gini coefficient decreasing from 0.310 to 0.263. The Gini coefficient in the year 2000 was 0.255, indicating only a slight improvement in 10 years from 1990 to 2000. CONCLUSIONS: The results suggest that the geographical distribution of dentists in Japan is influenced by municipalities' population size. While the number of dentists in municipalities with populations of less than 5000 increased during the years from 1980 to 2000, 25.9 percent of these municipalities still had no dentists at the end of this period. This is an important issue that warrants prompt corrective action. PMID- 21972465 TI - Oral health-related quality of life among low-income adults living with HIV. AB - OBJECTIVES: To explore oral health-related quality of life and its correlates among low-income human immunodeficiency virus (HIV)-positive patients receiving primary HIV care. METHODS: Data were from a randomized experimental trial evaluating an intervention to increase use of oral health services by low-income HIV-positive adults. Interviews were conducted in English or Spanish among 594 adults receiving HIV medical care but not dental care. Oral health-related quality of life was measured with the 49-item Oral Health Impact Profile (OHIP 49).Primary predictor variables included measures of HIV disease: duration of HIV infection, CD4 cell count, and HIV viral load. Other predictors included sociodemographic and behavioral factors. RESULTS: Overall, 62.6 percent of participants had experienced at least one oral health impact very often or fairly often in the 4 weeks preceding the survey, with a mean of 5.8 impacts. The mean number of impacts was significantly higher for women, the unemployed, those living in temporary housing, and current smokers. Neither the prevalence nor the mean number of impacts differed significantly by duration of HIV infection, CD4+ T lymphocyte cell count, or HIV viral load. In bivariate analysis, women had higher mean OHIP-49 scores than men overall (62.6 versus 50.5, P < 0.05) and for most subscales, indicating that women experienced more oral health impacts. In the final multivariate model, significant correlates of OHIP-49 were sex, race/ethnicity, living situation, and smoking status. CONCLUSIONS: Oral health impacts are prevalent among adults in South Florida living with HIV, particularly among women, cigarette smokers, those in prison or other institutional settings, and certain racial and ethnic groups. PMID- 21972466 TI - Predictors of oral health quality of life in HIV-1 infected patients attending routine care in Australia. AB - OBJECTIVE: To examine predictors of oral health quality of life (OHQoL) in a human immunodeficiency virus (HIV)-infected population undergoing routine HIV care in the era of antiretroviral therapy. METHOD: The study was an anonymous self-administered survey of 273 patients. Subjects completed the Oral Health Impact Profile-14 and questionnaires on sociodemographics, HIV, and dental issues. Multiple logistic regression analysis was conducted to determine the predictors of OHQoL. RESULTS: The study found smoking [odds ratio (OR) = 2.44], time to last dental visit (OR = 2.63), denture use (OR = 2.83), and income level (OR = 0.27) were significantly associated with OHQoL. No HIV-related variables predicted OHQoL. CONCLUSION: Smoking, not consulting a dentist in the last year, denture use, and low income were identified as significant predictors which could be targeted to improve quality of life among people living with HIV. Preventing dental diseases may also reduce the risk of activation of latent HIV by oral pathogens. PMID- 21972467 TI - Dental visits among adult Hispanics--BRFSS 1999 and 2006. AB - OBJECTIVES: This study examined and compared utilization of dental services by adult U.S. Hispanics 18 years and older in the years 1999 and 2006. METHODS: Dental utilization data collected by telephone interviews by the state-based Behavioral Risk Factor Surveillance System (BRFSS) were analyzed. RESULTS: In 2006, the state mean and median prevalence of adult Hispanics with dental visits during the past year were 56.2 percent and 62.1 percent, respectively, and had not changed significantly since 1999. In 40 states, utilization was well below the national prevalence of 70.3 percent. Frequency of dental visits was significantly higher among females and those with higher income (> $50,000), higher education, nonsmokers, and persons having medical health insurance. CONCLUSIONS: Findings from this study suggest that barriers to utilization of dental services among Hispanic adults exist in most states and may contribute to existing oral health disparities. The magnitude of this problem may increase in the future with the expansion of the U.S. Hispanic population. PMID- 21972468 TI - Intracellular signaling and the origins of the sensations of itch and pain. AB - The skin is the largest sensory organ of the body. It is innervated by a diverse array of primary sensory neurons, including a heterogeneous subset of unmyelinated afferents called C fibers. C fibers, sometimes classified as nociceptors, can detect various painful stimuli, including temperature extremes. However, it is increasingly evident that these afferents respond to various pruritic stimuli and transmit information to the brain that is perceived as itch; this can subsequently drive scratching behavior. Although itch and pain are distinct sensations, they are closely related and can, under certain circumstances, antagonize each other. However, it is not clear precisely when, where, and how the processes generating these two sensations originate and how they are dissociated. Clues have come from the analysis of the activities of specific ligands and their receptors. New data indicate that specific pruritic ligands carrying both itch and pain information are selectively recognized by different G protein-coupled receptors (GPCRs), and this information may be transduced through different intracellular circuits in the same neuron. These findings raise questions about the intracellular mechanisms that preprocess and perhaps encode GPCR-mediated signals. PMID- 21972469 TI - ["Des hommes noirs et non pas des negres": skin and race in XVIIIth century]. AB - A growing interest in the nature of the black skin and in the origins of the peoples classified under this trait was accompanied in the eighteenth century by an increasing differentiation of their nature from whites, to the point that they were considered either a degenerated variety of humans, a separate species or inferior animals. Skin and race go together in the natural history of man, which comprises not only anatomical and physiological aspects, but also the history of nations, the Sacred History, and the aesthetic reflection. PMID- 21972470 TI - [The discourse on mental disorders in the Hispanic short novel: Amado Nervo's case]. AB - The evolution of Amado Nervo's novellas shows a constant communication with the paradigmatic shifts in the field of psychopathology. His metafictional constructs foreground a playful treatment of some of medicine's key ideas. In some cases, the narrow limits of positivistic psychopathology are overcome in order to anticipate notions that obtain scientific status with modern psychology. PMID- 21972471 TI - [Francisco Ramirez Vas: press and medical philosophy in the third quarter of the 19th century]. PMID- 21972472 TI - [To the study of conventual health in the beginning of 19th century: the pharmacies]. AB - The institution "Junta do Exame do Estado Actual e Melhoramento Temporal das Ordens Regulares" (Examination Council for the Actual State and Temporal Improvement of the Religious Orders) was created in November of 1789. Among other things, each Religious House should inform that institution about its heritage either the movables and the landed estates. The inventorying included all the goods belonging to wards and drugstores. In this paper, we aim to study those places using records obtained from a variety of Religious Houses with no regional or Religious Order preferences. We will try to give answers to questions related to that spaces such as 'Which objects could be found inside the Houses?'; 'Were they properly equipped?'; and 'Were there big differences between them in what concerns Religious Orders and Houses locations?'. PMID- 21972473 TI - "Mathematics made no contribution to the public weal": why Jean Fernel (1497 1558) became a physician. AB - This paper offers a caution that emphasis upon the importance of mathematics in recent historiography is in danger of obscuring the historical fact that, for the most part, mathematics was not seen as important in the pre-modern period. The paper proceeds by following a single case study, and in so doing offers the first account of the mathematical writings of Jean Fernel (1497-1558), better known as a leading medical innovator of the 16th century. After establishing Fernel's early commitment to mathematics, and attempt to forge a career as a cosmographer, it goes on to explain his abandonment of mathematics for a career in medicine. The 'mathematization of the world picture' is usually explained in terms of the perceived usefulness of mathematics, but Fernel's case shows that for many pre modern thinkers, mathematics was not regarded as a useful pursuit. The paper should serve as a reminder, therefore, that the take-up of mathematics by natural philosophers was by no means inevitable, but had to be carefully managed by early modern mathematical practitioners. The case of Fernel indicates that perhaps he was not the only would-be mathematical practitioner to abandon mathematics in favor of a calling that was more appreciated by contemporaries. PMID- 21972474 TI - Constructing a scientist: expert authority and public images of Rachel Carson. AB - This article uses the voluminous public discourse around Rachel Carson and her controversial bestseller "Silent Spring" to explore Americans' views on science and scientists. Carson provides a particularly interesting case study because of intense and public debates over whether she was a scientist at all, and therefore whether her book should be granted legitimacy as science. Her career defied easy classification, as she acted variously as writer, activist, and environmentalist in addition to scientist. Defending her work as legitimate science, which many though not all commentators did, therefore became an act of defining what both science and scientists could and should be. This article traces the variety of nonscientific images and narratives readers and writers assigned to Carson, such as 'reluctant crusader' and 'scientist-poet'. It argues that nonscientific attributes were central to legitimating her as both admirable person and admirable scientist. It explores how debates over "Silent Spring" can be usefully read as debates over the desirability of putatively nonscientific attributes in the professional work of a scientist. And it examines the nature of Carson's very democratized image for changing notions of science and scientists in 1960s United States politics and culture. PMID- 21972475 TI - Infectious disease modeling and military readiness. PMID- 21972476 TI - Lymphatic filariasis. PMID- 21972477 TI - Impact of polystyrene beads as a mosquito control measure to supplement lymphatic filariasis elimination activities in Socotra Island, Yemen. AB - Lymphatic filariasis (LF) is targeted for worldwide elimination. In Yemen, all mainland implementation units met the WHO criteria for stopping mass drug administration (MDA) after 5 rounds. However, in Socotra Island these criteria were not met. Our study evaluated the efficacy of applying expanded polystyrene beads (EPBs) on the Culex population and the effect on LF transmission. Human and mosquito surveys were conducted in 40 randomly selected households in Hadibo (capital of Socotra) before and after application of EPBs. The EPBs intervention resulted in a reduction in mosquito density of 80% and a 64.3% reduction in microfilaria prevalence. The majority of interviewed households (98%) thought EPBs considerably reduced the mosquito population. After the intervention all collected pools tested negative. Application of EPBs is an effective supplement to MDA for achieving the goal of LF elimination. PMID- 21972478 TI - Staff views about the quality of the Communicable Diseases Surveillance System in Khartoum State, Sudan, 2005-2007: a qualitative study. AB - Surveillance staff are vital to the success of surveillance of infectious diseases. In this study, we interviewed staff of the Communicable Diseases Surveillance System (CDSS) in Khartoum state individually and in focus groups to assess their views about the quality of the system for the years 2005-07. The quality of CDSS was considered poor because the system was not representative as it included neither the private nor military sectors nor the important teaching hospitals. It also lacked timeliness due to poor documentation, was inflexible since it did not rapidly respond to emerging and re-emerging diseases such as SARS and avian flu in its notification lists, and it did not use the data collected to apply interventions for control and prevention of communicable diseases on a routine basis. While staff were committed to the surveillance system and felt they worked hard, they were also demotivated and in the long run this might affect their performance. PMID- 21972479 TI - Pilot study of sunlight exposure and vitamin D status in Arab women of childbearing age. AB - Vitamin D deficiency is common in Arab women. In a pilot study we investigated the effect of sun exposure at recommended levels on the vitamin D status of Arab women. Eight healthy Arab women of childbearing age consented to expose their face, arms and hands for 15 minutes per day twice a week for 4 weeks within the privacy of their courtyard and to avoid changes in dietary vitamin D intake. Serum 25-hydroxyvitamin D [25(OH)] levels were measured pre- and post intervention. Although vitamin D levels remained sub-optimal median serum 25(OH)D levels were significantly higher post-intervention (23.0 nmol/L) than pre intervention (17.6 nmol/L). Extending sun exposure for more than 4 weeks should be investigated as part of strategies to improve vitamin D status in high-risk Arab women who lack outdoor sun exposure to the skin. PMID- 21972480 TI - Adiponectin levels in serum of women with preeclampsia. AB - However, reports of the role of adiponectin in pre-eclampsia are conflicting. This study in Egypt investigated the association between serum adiponectin levels and pre-eclampsia and between adiponectin levels and some clinical and hormonal parameters. A sample of 60 pregnant women in the third trimester were divided into 3 equal groups: normal pregnancy, mild pre-eclampsia and severe pre eclampsia. Serum adiponectin levels in pre-eclamptic women were significantly higher than in normal pregnant women and the increase was more marked in cases of severe pre-eclampsia. There was a significant negative correlation between adiponectin levels and arterial blood pressure in all groups. However, there was no correlation between serum adiponectin and proteinuria or estradiol and progesterone levels. The results support the theory that adiponectin might be part of a feedback mechanism improving insulin sensitivity and cardiovascular health in pre-eclamptic patients. PMID- 21972481 TI - Histological findings in women with postmenopausal bleeding: Jordanian figures. AB - Postmenopausal bleeding represents one of the most common reasons for referral to gynaecological services. A retrospective review was made of the hospital records of 482 women presenting with postmenopausal bleeding to a referral hospital in Amman, Jordan. Histopathological reports and patients' records were reviewed and different causes of bleeding were identified and related to patients' age. Adenocarcinoma was responsible for 9% of cases, and hyperplasia for 11%. Atrophy of the endometrium was the most common finding (52% of women), followed by hyperplasia (with and without atypia) (11%) and carcinoma (9%). The risk of cancer increased with increasing age while the incidence of bleeding decreased with age. Other pathology was reported as the main finding in 11 cases (2%) with postmenopausal bleeding. These preliminary data are the first reports from Jordan of histopathological findings in this group of patients, and a larger study is required to establish national figures. PMID- 21972482 TI - Prevalence and risk factors of erectile dysfunction among patients attending primary health care centres in Qatar. AB - Erectile dysfunction is a common health problem affecting the quality of life of men of all ages. The aim of this study was to find the prevalence of and significant risk factors for erectile dysfunction among men of all nationalities attending primary health care centres in Qatar for any reason. Respondents aged > 30 years (n = 1139) completed the sexual health inventory for men plus a questionnaire about their demographic characteristics, lifestyle habits and presence of chronic diseases. The total prevalence of erectile dysfunction was 56.9% (32.7% mild and 2.3% severe cases). All studied sociodemographic variables showed a significant association with erectile dysfunction. A lower prevalence of erectile dysfunction was found in smokers and those who exercised. More than 1 sexual partner, obesity and having a chronic disease (hypertension, coronary heart disease, hypercholesterolaemia or diabetes mellitus) were significantly positively associated with erectile dysfunction. PMID- 21972483 TI - Prevalence of stress among Iranian medical students: a questionnaire survey. AB - A cross-sectional study measured the frequency of self-reported stress symptoms among a weighted random sample of medical students in Isfahan, Islamic Republic of Iran. The data were gathered using the Kessler 10-item psychological distress scale. The overall prevalence of stress among 222 students was 61.3% and there were no statistically significant differences in stress levels between students in the pre-clinical and clinical phases or different years of study. Married students had significantly lower scores than single students but there were no differences between the sexes. Students who chose to study medicine had lower stress scores than those who were influenced by family or had no choice about the subject. Students with mild to moderate stress were significantly more likely to suffer physical problems (OR = 4.42). Interventions are needed to tackle stress and improve Iranian medical students' physical and psychological well-being. PMID- 21972484 TI - Assessment of parental awareness about malocclusion in Shiraz, Islamic Republic of Iran. AB - Information empowers people to take charge of their health. The aim of this study in Shiraz, Islamic Republic of Iran was to evaluate parents' knowledge about dental malocclusion, referral routes and information sources. A random sample of 1000 7-9-year-old schoolchildren were given a questionnaire to complete at home. Questionnaires were completed by 795 parents. Knowledge about malocclusion was significantly greater in families with higher levels of education and income. Most respondents (83.5%) were aware of the importance of maintaining primary teeth to prevent malocclusion, and 25.1% thought that carious primary teeth must be extracted. Half of the parents (50.6%) did not know that spaces between primary teeth are normal. Only 28.8% of the children visited dentists for annual routine check-ups. Television (43.3%) was the most common source of dental information. The level of general public awareness about malocclusion needs to be improved. PMID- 21972485 TI - Skin prick test reactivity to aeroallergens in Jordanian allergic rhinitis patients. AB - Identification of the most common aeroallergens to which patients are sensitized in a specific area is important in the diagnosis and treatment of allergic rhinitis. The aim of this cross-sectional study was to investigate the pattern of skin prick test reactivity to various aeroallergens among allergic rhinitis patients attending outpatient clinics in Amman, Jordan. Skin prick test with 18 standardized allergen extracts was performed on 538 patients. Most allergic rhinitis patients in the study sample had polysensitization. Grasses mix (51.4% of patients), thistleweed (46.9%) and olive tree (45.3%) pollens were the most common allergens in this group of patients (all seasonal). Cat allergen was the most common perennial allergen (41.6%), followed by dust mite Dermatophagoides pteronyssinus (32.9%). These allergens should be given the highest priority when educating allergic rhinitis patients in Amman regarding allergen avoidance strategies. PMID- 21972486 TI - Etiology of pleural effusion among adults in the state of Qatar: a l-year hospital-based study. AB - There have been no systematic studies of diseases causing pleural effusion in Qatar. This prospective, hospital-based study involved all adult patients (> 15 years) with pleural effusions who were admitted to referral hospitals over a 1 year period. A total of 200 cases of pleural effusion were identified (152 males and 48 females); mean age 45.1 (SD 18.5) years. A majority of patients (73.5%) were non-Qataris, mostly from the Asian subcontinent. The most frequent cause of pleural effusions was tuberculosis (32.5%), followed by pneumonia (19%), cancer (15.5%) and cardiac failure (13%). The most frequent cause of malignant effusion was bronchogenic carcinoma (38.7%), whereas Gram-positive organisms were the most frequent isolates from empyema fluid (62.5%). Histological examination and culture of pleural biopsy were the most useful diagnostic workup for tuberculosis effusions, whereas repeated cytological examination of pleural fluid and pleural biopsy were most useful for malignant effusions. PMID- 21972487 TI - The state of affairs at primary health care facilities in Pakistan: where is the state's stewardship? AB - Primary health care (PHC) services in Pakistan, particularly in rural areas, are in a dismal state. Inadequacies, unfairness and ignorance about the importance of the basic health care provided by these facilitates have led to a disorganized and poorly performing system. This paper reviews the situation in certain PHC facilities in Sindh province. Inadequate medicines and supplies, underutilized family planning services, lack of human resources, faulty equipment, and absence of a proper referral mechanism were some of the key findings. There is therefore an urgent need for radical improvement in the PHC system in order to maximize the appropriate use of PHC facilities. In order to do this, the paper argues that the stewardship role of the State must be strengthened. PMID- 21972488 TI - Ethics of medical care for body packers (drug smugglers): untangling a web of fears and conflicts of interest. AB - Body packing by drug smugglers--the transport of illicit drugs in packets swallowed or inserted into body cavities--is a global phenomenon and is becoming more prevalent. The medical care of these patients raises difficult medical and ethical problems. While the medical aspects of treating body packers have been systematically analysed, the ethical issues have received little attention in the literature. The patient may be under police custody or being sought by their criminal patron which may result in imposed interrogations and risky medical procedures. Obtaining informed valid consent for procedures from the patient detainee may thus be compromised. In addition, physicians may be intimidated by the patient's criminal contacts. This article analyses the conflicts of interest that doctors may face when treating body packers, and proposes some principles to promote institutional guidelines for the treatment of these patients. PMID- 21972489 TI - The need for capacity building to prevent chronic diseases in North Africa and the Middle East. AB - Chronic (noncommunicable) diseases, such as cardiovascular disease, stroke, cancer and diabetes mellitus, are a global public health problem that is increasing, particularly in developing countries. According to the World Health Organization, over the period 2006-15, the largest increase in deaths from chronic diseases will occur in the regions of Africa and the Middle East. This article outlines the problems facing theses regions with regard to chronic diseases, and discusses the urgent need for capacity building and community-based programmes in order to enhance regional capability for tackling chronic diseases. PMID- 21972490 TI - The 21st century demand for sociopolitical reforms in the Middle East: will there be a fair focus on the health sector? PMID- 21972491 TI - The potential of Chromolaena odorata (L) to decontaminate used engine oil impacted soil under greenhouse conditions. AB - This study reports on the use of Chromolaena odorata (L) R.M. King and H. Robinson, an Asteraceae (compositae) and an invasive alien weed in Africa for the remediation of soil contaminated with used engine oil. Used engine oilfrom a motor service garage was used to artificially contaminate soil taken from a garden to give total petroleum hydrocarbon (TPH) of between 1 and 40 g kg(-1). Chromolaena odorata (L), propagated by stem cuttings were transplanted into the contaminated soil and watered just enough to keep the soil at about 70% water holding capacity for 90 day. A set of control experiments containing 40 g kg(-1) used engine oil but without plants was set up. All experiments were set up in triplicates. Although the plants in the experiments containing higher than 30 g kg(-1) used engine oil showed relatively slower growth (fewer branches and leaves, and shorter in height) compared to those containing lower concentrations, the plants in all the experiments continued to grow until the end of the 90 day period. Residual TPH after 90 days showed that between 21 and 100% of oil was lost from the planted soil while only 11.5% was lost in the control, which did not contain plants during the same period. Analysis of plant tissues showed that both shoot and root tissues contained detectable levels of TPH and selected PAHs were also detectable. Biomass accumulation by Chromolaena odorata was affected adversely by concentrations of oil higher than 20 g kg(-1). Results of germination rates and germination energy measurements showed that Chromolaena odorata was able to reduce the toxicity of the contaminated soil after 90 days as compared to soils containing freshly contaminated soiL PMID- 21972492 TI - Callus cultures for phytometabolism studies: phytometabolites of 3 trifluoromethylphenol in Lemnaceae plants and callus cultures. AB - Plant callus cultures have the potential to advance phytoremediation science by allowing study of cellular phytometabolism in absence of sorption, translocation, microbial degradation, and other phytoremediation processes; however, studies demonstrating the applicability of results from callus cultures to whole plants are limited. The aim of this study was to evaluate the feasability and applicability of using callus cultures to study phytometabolism. This aim was accomplished through evaluation of induction and growth of Lemnaceae callus cultures and comparison of phytometabolism in callus cultures and whole plants. Four out of eight published methods for callus culture of Lemnaceae successfully induced callus cultures that exhibited doubling times of 1.7 to 23 wks. Callus cultures and whole plants of Landoltia punctata and Lemna minor metabolized 3 trifluoromethylphenol (3-TFMP) through conjugation with glucopyranoside, malonyl glucopyranoside, and glucopyranosyl-apiofuranoside. However, concentrations of metabolites were approximately 10 times less in callus cultures than in plants. While results demonstrated applicability of callus cultures results to whole plants, the low success rate of callus induction procedures, length of time required to produce substantial callus mass, and the low accumulation of metabolites in callus cultures may limit the feasibility of callus cultures for assessing phytometabolism. PMID- 21972493 TI - Enhanced arsenic tolerance of transgenic eastern cottonwood plants expressing gamma-glutamylcysteine synthetase. AB - Arsenic is a metalloid that occurs naturally at parts per million (ppm) levels in the earth's crust. Natural and human activities have contributed to arsenic mobilization and increased concentration in the environment, such that World Health Organization guidelines for arsenic levels in drinking water are exceeded at many locations, worldwide. This translates into an increased risk of arsenic related illnesses for millions of people. Recent studies demonstrate that increasing thiol-sinks in transgenic plants by overexpressing the bacterial gamma glutamylcysteine synthetase (ECS) gene results in a higher tolerance and accumulation of metals and metalloids such as cadmium, mercury, and arsenic. We used Agrobacterium-mediated transformation to genetically engineer eastern cottonwood with a bacterial ECS gene. Eastern cottonwood plants expressing ECS had elevated thiol group levels, consistent with increased ECS activity. In addition, these ECS-expressing plants had enhanced growth on levels of arsenate toxic to control plants in vitro. Furthermore, roots of ECS-expressing plants accumulated significantly more arsenic than control roots (approximately twice as much), while shoots accumulated significantly less arsenic than control shoots (approximately two-thirds as much). We discuss potential mechanisms for shifting the balance of plant arsenic distribution from root accumulation to shoot accumulation, as it pertains to arsenic phytoremediation. PMID- 21972494 TI - Seeding conditions of the halophyte Atriplex patula for optimal growth on a salt impacted site. AB - Salt-impacted soils resulting from oilfield brine spills are increasingly becoming a significant problem in oil-producing areas of Canada such as Alberta and Saskatchewan. The native halophyte Atriplex patula is being considered a potential species for phytoremediation of brine-impacted sites in these hemiboreal climactic zones. The objective of this study was to investigate the optimal seeding conditions under field conditions (with no irrigation) of A. patula for phytoremediation of salt from a brine-impacted site. Atriplex patula was identified in preliminary greenhouse trials to have one of the highest salt accumulations in relation to plant yields. Different seeding methods of A. patula were assessed in an attempt to achieve reproducible growth of this species. While plant yields for A. patula were improved on compacted soil by approximately 30 50%, growth was uneven with regard to density and height. The uneven growth may be due to seed quality and low precipitation during the field season, while improvements in plant yield on compact soil might be due to a lack of competition with other species. PMID- 21972495 TI - Plant species potentially useful in the phytostabilization process for the abandoned CMC mining site in northern Cyprus. AB - The Cupper Mining Company (CMC)'s site located in Lefke-Gemikonagi, Northern Cyprus has been a continuous source of highly dangerous contamination for the surrounding environment, the Lefke region, and the neighboring ecosystems and settlements. Rehabilitation and reuse possibilities of the CMC site due to its vital importance have kept its place in the agenda of Northern Cyprus. Phytostabilization appears to be a convenient and less expensive method that can immediately be used for reducing the negative impacts of the mining site on the region. The main purpose of this study is to identify potential candidate plant species, adapted to grow on polluted sites, for revegetation in the CMC site. Within this context, the method of the study can be summarized as follows: literature review for examining potential candidate plant species for pyhtostabilization in arid and semiarid regions, especially the ones suitable both for the existing ecological and present conditions of Cyprus; identification of native and/or cultural plant species survived in the heavily polluted mining site, and definition of a number of candidate plant species for the study site. The result of sampling revealed that 23 plant species thrive well in the contaminated site. As a result of the literature review and considering drought, metal, salt tolerant features of semiarid environment in the region, 5 tree, 4 shrub, and 23 herbaceous plant species were proposed for starting revegetation with the purpose of phytostabilization on the CMC mining site. PMID- 21972496 TI - Total phosphorus removal from domestic wastewater with Cyperus alternifolius in vertical-flow constructed wetlands at the microcosm level. AB - Vertical-flow constructed wetland (VFCW) is an effective alternative for removal of nutrients, heavy metals, and organic pollutants from wastewaters. This study investigated the uptake and removal of total phosphorus (TP) by Cyperus alternifolius from domestic wastewaters in the simulated VFCWs, The total of eight simulated VFCW treatments, including two different substrates, two different wet-to-dry ratios, and with and without C. alternifolius species (2 x 2 x 2 = 8), were utilized for an operation period of two years in this study. Results show that about 1.1 to 1.4 times more TP was removed from the influent with the presence of C. alternifolius as compared to without this plant species. A linear correlation existed between the aboveground biomass and its TP content. An increase in total biomass by 1000 g would result in an increase in TP accumulation in the aboveground biomass by 4.9 g. Large amounts of TP were removed by the substrate adsorption as compared to those by the aboveground biomass. Results suggest that, although substrate adsorption played a major role in TP removal, C. alternifolius uptake was an alternative pathway for further removal of TP from wastewaters in the VFCWs. PMID- 21972497 TI - The effect of ethylene glycol on the phytovolatilization of 1,4-dioxane. AB - Phytoremediation at contaminated sites is often complicated by the presence of more than one chemical However, the effects of common co-contaminants such as ethylene glycol on the phytoremediation of other chemicals, e.g., 1,4-dioxane, is not well understood. Field studies with DN34 poplar trees revealed a 28% decline in growth rate in response to 10 g/L ethylene glycol in the groundwater, thus indicating a significant and deleterious effect on tree viability, and likely, the plants' utility for phytoremediation. Thorough investigations using Arabidopsis thaliana, with its small size and rapid life cycle, indicated significant growth reduction at 10 g/L and complete inhibition of germination at 40 g/L ethylene glycol Ethylene glycol was almost as severe a stressor as the well characterized osmotic inhibitor, sorbitoL Watering potted trees with 10 g/L ethylene glycol reduced their growth by more than 50%, and similar results were observed in hydroponically grown poplar and willow trees. Under hydroponic conditions, 60 g/L ethylene glycol inhibited the phytovolatilization of l,4 dioxane by more than 80%, and all trees evapo-transpired 1,4-dioxane less efficiently than water. In fact, this efficiency differed between trees and the difference became more pronounced in the presence of ethylene glycol. PMID- 21972498 TI - Phytoextraction of heavy metals from contaminated soil by co-cropping with chelator application and assessment of associated leaching risk. AB - Phytoextraction using hyperaccumulating plants is generally time-consuming and requires the cessation of agriculture. We coupled chelators and a co-cropping system to enhance phytoextraction rates, while allowing for agricultural production. An experiment on I m3 lysimeter beds was conducted with a co-cropping system consisting of the hyperaccumulator Sedum alfredii and low-accumulating corn (Zea Mays, cv. Huidan-4), with addition ofa mixture of chelators (MC), to assess the efficiency of chelator enhanced co-crop phytoextraction and the leaching risk caused by the chelator. The results showed that the addition of MC promoted the growth of S. alfredii in the first crop (spring-summer season) and significantly increased the metal phytoextraction. The DTPA-extractable and total metal concentrations in the topsoil were also reduced more significantly with the addition of MC compared with the control treatments. However, mono-cropped S. alfredii without MC was more suitable for maximizing S. alfredii growth and therefore phytoextraction of Zn and Cd during the autumn-winter seasons. No adverse impact to groundwater due to MC application was observed during the experiments with three crops and three MC applications. But elevated total Cd and Pb concentrations among subsoils compared to the initial subsoil concentrations were found for the co-crop + MC treatment after the third crop. PMID- 21972499 TI - Batch and continuous removal of arsenic using hyacinth roots. AB - Arsenic is considered a primary pollutant in drinking water because of its high toxicity. The unique property of water hyacinth roots (Eichhornia crassipes) to remove heavy metals is of great signiicance for the development of a cost effective phytoremediation technology. An experimental test program was conducted at the United States Environmental Protection (USEPA) Test and Evaluation (T&E) Facility in Cincinnati, Ohio, to investigate the potential of water hyacinth roots to remove arsenic from spiked drinking water samples. Water hyacinth roots were washed, dried, and powdered to provide dried hyacinth roots (DHR) for batch and continuous column experiments, Various quantities of DHR were added to water spiked with 300 micrograms per liter (microg/L) arsenic. A concentration of 20 g/L DHR was found adequate for greater than 90% arsenic removal in the batch tests. Based on the batch test results, continuous column experiments were performed using a 2-L column. In a continuous system, 15 L of water containing 300 microg/L arsenic were treated to below 20 microg/L using 50 g DHR, and 44 L of water containing 600 microg/L arsenic were treated to below 20 microg/L using 100 g DHR, giving a specific accumulation rate of approximately 260 microg As/g DHR. PMID- 21972500 TI - Effects of light regime, temperature, and plant age on uptake of arsenic by Spartina pectinata and Carex stricta. AB - We report here on efforts to show that a combination of native wetland plant species might perform better than a monoculture in wetlands designed for arsenic remediation by supplementing weaknesses. Carex stricta and Spartina pectinata were used in hydroponic experiments. (i) Arsenic uptake was first assessed at two ages via exposure to control or arsenic-laden solutions (0 or 1.5 mg As L(-1) as Na2HAsO4) for two weeks. Age had no significant effect on arsenic concentrations in roots, but translocation factors were greater in older plants of C. stricta and S. pectinata (0.45 and 0.07, respectively) than in younger plants (0.10 and 0.01, respectively). (ii) Seasonal effects were assessed by determining uptake kinetics for both species in conditions representative of spring temperatures (15/5 degrees C) and light regimes (1050 micromol m(-2) s(-1), 13 h day(-1)) and summer temperatures (28/17 degrees C) and light regimes (1300 micromol m(-2) s( 1), 15 h day(-1)). Both species had comparable rates of arsenic uptake into roots in summer conditions (44.0 and 46.5 mg As kg(-1) dry wt. h(-1) in C. stricta and S. pectinata, respectively), but C. stricta had a higher maximum net influx rate in spring conditions (24.5 versus 10.4 mg As kg(-1) dry wt. h(-1)). PMID- 21972501 TI - Lead, chromium and manganese removal by in vitro root cultures of two aquatic macrophytes species: Typha latifolia L. and Scirpus americanus pers. AB - The ability of in vitro roots cultures of Typha latifolia and Scirpus americanus to remove metals was studied. Roots were cultivated on Murashige-Skoog medium with 15 microg L(-1) Cr 11, 60 microg L(-1) Pb II or 1.8 mg L(-1) Mn II. Adsorbed metal to root surface was removed by washing with 0.042% HNO3. T. latifolia roots were able to uptake 68.8 microg Pb g(-1), 22.1 microg Cr g(-1) and 1680 microg Mn g(-1), while the S. americanus roots removed 148.3 microg Pb g(-1), 40.7 microg Cr g(-1) and 4037 microg Mn g(-1). About 80-90% of Pb and Cr were absorbed in both cultures. On the contrary, the Mn removal was due mainly to an adsorption process (82-86%). In comparison to the T. latifolia cultures, S. americanus cultures were twofold more efficient to remove Pb and Cr, and threefold more efficient to remove Mn. Both plant species capture metals in the following order: Cr >Pb >Mn. This investigation confirms that in vitro roots cultures could be an alternative as a phytoremediation approach for contaminated water with heavy metals. PMID- 21972502 TI - Amendments promote the development of Lolium perenne in soils affected by historical copper smelting operations. AB - The Puchuncavi valley, central Chile, has been exposed to aerial emissions from a copper smelter. Nowadays, soils in the surroundings are sparsely-vegetated, acidic, and metal-contaminated, and their remediation is needed to reduce environmental risks. We assessed effectiveness of lime, fly ash, compost, and iron grit as amendments to immobilize Cu in soils and promote plant growth. Amended soils were cultivated with Lolium perenne for 60 days under controlled conditions. Total dissolved Cu and Cu2+ activity in the soil solution, ryegrass biomass, and Cu accumulation in plant tissues were measured. Addition of lime and fly ash decreased Cu concentrations and Cu2+ activity in the soil solution, increased plant biomass, and reduced shoot Cu concentration below 22 mg kg(-1) (the phytotoxicity threshold for the species). The most effective amendment with respect to the shoot biomass yield was a combination of lime and compost. Water content of the substrate and the K accumulation were positively correlated with the compost application rate. Compost combined with iron grit decreased dissolved Cu concentrations during the period of highest solubility, i.e., during the first 60 days after the compost application. However, iron grit incorporation into soils amended with lime and compost decreased the shoot biomass of ryegrass. PMID- 21972503 TI - Phytoextraction of cadmium by four Mediterranean shrub species. AB - The possibility of remediating contaminated soils though the use of high biomass generating, native plant species capable of removing heavy metals is receiving increased attention. The cadmium (Cd) accumulation capacities of the native Mediterranean, perennial shrubs Atriplex halimus, Phyllirea angustifolia, Rhamnus alaternus and Rosmarinus officinalis were tested by growing transplanted specimens in a pine bark compost substrate (pH 5.6) contaminated with 100 mg Cd kg(-1). After 70 days, only R. alaternus showed reduced growth. The increase in biomass seen in all the test species enhanced the phytoextraction of Cd. However, the species behaved as metal excluders, except for the halophyte A. halimus, which behaved as an indicator plant. In this species the leaf Cd concentration reached 35 mg Cd kg(-1), with the shoot responsible for some 86% of total Cd accumulation. Atriplex halimus showed the highest bioconcentration factor (BCF) (0.36) and leaf Cd transport index (1.68); consequently, this species showed the highest Cd phytoextraction capacity. PMID- 21972504 TI - Phytoremediation of Cd, Cr, Cu, Mn, Fe, Ni, Pb and Zn from aqueous solution using Phragmites cummunis, Typha angustifolia and Cyperus esculentus. AB - A comparative bioaccumulation pattern and ultra structural changes were studied in Phragmites cummunis, Typha angustifolia and Cyperus esculentus in mixed metals solution of cadmium (Cd), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), lead (Pb) and zinc (Zn). P. cummunis was observed to be a shoot accumulator for Cr, Fe, Mn, Ni, Pb, and Zn. However, T. angustifolia was found to be a root accumulator for Cd, Cr, Cu, Fe, Ni and Pb. In addition, C. esculentus also accumulated most of the tested heavy metals in the roots, while Mn and Fe were translocated up to leaves. Further, the long term metal treatment showed maximum accumulation of all heavy metals in P. cummunis followed by T. angustifolia and C. esculentus. Among heavy metals, Fe was accumulated maximum, i.e., >1000 microg g(-1) by all three plants. Simultaneously, the adverse effects on biochemical parameters were noted earlier in C. esculentus than T. angustifolia and P. cummunis. Ultra structural observation showed the cellular changes in wetland plants after longer exposure. Results revealed that P. cummunis and T. angustifolia had more potential for tested metals than C. esculentus. This study established that these wetland plants could be used for heavy metals phytoremediation from metal containing industrial wastewater. PMID- 21972505 TI - Phytoremediaton of diethylene glycol contaminated wastewater by Echinodorus cordifolius. AB - Diethylene glycol (DEG) is one of several diols used as a raw material in the production of plasticizers and polyester resins. It has been associated with a number of mass poisonings in several countries. Conventional methods of remediation of DEG contaminated wastewaters are still not very effective. This paper presents an alternative method for remediation of DEG-contaminated waters using the plant Echinodorus cordifolius. The effects of DEG on E. cordifolius were studied along with the plant's efficiency at treating DEG-contaminated wastewater in a constructed wetland. We found that DEG was toxic to the plants with an LD50 of 6238 mg L(-1). The plants exhibited decreased water uptake and showed wilting, chlorosis and necrosis. SEM images showed injury to the cortex tissue. In the constructed wetland, E. cordifolius plants were able to remove and degrade DEG from wastewater, decreasing the pH from 12 to 6.8 and the COD and TDS by approximately 98% and 67%, respectively, in 7 days, while accumulating Ca in the cells. PMID- 21972506 TI - Potential use of Lemna minor for the phytoremediation of isoproturon and glyphosate. AB - Pesticides are being detected in water bodies on an increasingly frequent basis. The present study focused on toxicity and phytoremediation potential of aquatic plants to remove phytosanitary products from contaminated water. We investigated the capacity of Lemna minor (L. minor) to eliminate two herbicides isoproturon and glyphosate from their medium. Since phytoremediation relies on healthy plants, pesticide toxicity was evaluated by exposing plants to 5 concentrations (0-20 microg L(-1) for isoproturon and 0-120 microg L(-1) for glyphosate) in culture media for 4 d using growth rate and chlorophyll a fluorescence as endpoints. At exposure concentrations of 10 microg x L(-1) for isoproturon and 80 microg x L(-1) for glyphosate, effects on growth rate and chlorophyll fluorescence were minor (< 25%), so that this initial concentration was selected to study herbicide removal After a 4-d incubation, removal yields were 25% and 8% for isoproturon and glyphosate, respectively. PMID- 21972507 TI - Phytoremediation and removal mechanisms in Bouteloua curtipendula growing in sterile hydrocarbon spiked cultures. AB - Tolerance index and phytoremediation factors of side oats grama (Bouteloua curtipendula) with recalcitrant polycyclic aromatic hydrocarbons (PAH) phenanthrene (PHE), pyrene (PYR), and benzo[a]pyrene (BaP) and the resulting impact on phenotypic response, were evaluated in sterile conditions with whole plant growing in test-tube cultures with MS medium with PAH and compared with Tall fescue (Festuca arundinacea), control for this study. PAH mixture of PHE, PYR and BaP (1:1:1 w/w/w) blended with Maya crude oil (1:1 w/w), final concentration of 1500 mg kg(-1) was used. After 40 days, BaP removal, in the presence of Maya crude was superior compared with PHE and PYR removal Although the presence of PAH negatively affects the phenotypic response of the plants; sterile conditions experiments were helpful to evaluate phytoremediation factors to elucidate some important questions regarding phytoremediation mechanisms; in this study, B. curtipendula was able to phytostabilizate BaP associated to a significant hydrocarbon removal (57.4%) with high root accumulation but attenuated transport to stems, here reported as translocation factor. To our knowledge, this is the first time that quantifiable phytoremediation factors were used to evaluate the tolerance and removal capacity of a native semi-arid climate plant which is probably able to phytoremediate hydrocarbon contaminated soils. PMID- 21972508 TI - Irrigating poplar energy crops with landfill leachate negatively affects soil micro- and meso-fauna. AB - Increased municipal solid waste generated worldwide combined with substantial demand for renewable energy has prompted testing and deployment of woody feedstock production systems that reuse and recycle wastewaters as irrigation and fertilization. Populus selections are ideal for such systems given their fast growth, extensive root systems, and high water usage rates. Maintaining ecological sustainability (i.e., the capacity for an ecosystem to maintain its function and retain its biodiversity over time) during tree establishment and development is an important component of plantation success, especially for belowground faunal populations. To determine the impact of solid waste leachate on soil micro- and meso-fauna, we compared soilfrom eight different Populus clones receiving municipal solid waste landfill leachate irrigation with clones receiving fertilized (N, P K) well water irrigation. Microfauna (i.e., nematodes) communities were more diverse in control soils. Mesofauna (i.e., insects) were associated with all clones; however, they were four times more abundant around trees found within the control plot than those that received leachate treatments. Nematode and insect abundance varied among Populus clones yet insect diversity was greater in the leachate-treated soils. Phytotechnologies must allow for soil faunal sustainability, as upsetting this balance could lead to great reductions in phytotechnology efficacy. PMID- 21972509 TI - The use of water lettuce (Pistia stratiotes L.) for rhizofiltration of a highly polluted solution by cadmium and lead. AB - The effectiveness of heavy metal uptake from contaminated nutrient solution by four aquatic macrophytes (Pistia stratiotes L., Salvinia auriculata AubL, Salvinia minima Baker, and Azolla filiculoides Lam) was estimated in this study. The influence of cadmium (3.5 mg L(-1) and 10.5 mg L(-1)) and lead (25 mg L(-1) and 125 mg L(-1)) on the stress symptoms was observed through the determination of chlorophyll content and transpiration rate over 14 days of the experiment. The results of the present study showed extreme reductions in Cd and Pb concentrations in solution during the first 4 days. The accumulation of Pb in plant tissues was the highest during the first 4 days and was more than 10 times higher in the roots (42,862 mg kg(-1)) than in the leaves (3867 mg kg(-1)). The accumulation of Cd slowly increased and was the highest at the end of the experiment. Concentrations in roots (3923 mg kg(-1)) were roughly 6 times higher than in the leaves (624 mg kg(-1)). Results showed significant decrease in the transpiration rate at Pb treatment and a significant increase at Cd treatment during 48 hours of exposition. PMID- 21972510 TI - Reclamation of highly calcareous saline sodic soil using Atriplex halimus and by product gypsum. AB - The removal of sodium salts from saline soils by salt tolerant crops, as alternative for costly chemical amendments, has emerged as an efficient low cost technology. Lysimeter experiments were carried out on a highly saline sodic soil (ECe = 65.3 dS m(-1), ESP = 27.4, CEC = 47.9 cmole+ kg(-1), and pH = 7.7) and irrigated with canal water (EC = 2.2 dSm(-1), SAR = 4.8) to investigate reclamation efficiency under four different treatments: control (no crop and no gypsum application) (C), gypsum application equivalent to 100% gypsum requirement (G100), planting sea orach (Atriplex halimus) as phytoremediation crop (Cr), planting sea orach with gypsum application equivalent to 50% gypsum requirement (CrG50). Soil salinity (ECe) and exchangeable sodium percentage (ESP) were significantly reduced compared to the control. Average ESP and ECe (dS m(-1)) in the top layer were 9.1, 5.8 (control), 4.8, 3.7 (Cr), 3.3, 3.9 (CrG50), and 3.8, 3.1 (G100), respectively. Atriplex halimus can be recommended as phytoremediation crop to reclaim highly saline sodic clay loam soils. PMID- 21972511 TI - Effect of nitrogen and phosphorus concentration on their removal kinetic in treated urban wastewater by Chlorella vulgaris. AB - This study evaluates the feasibility of removing nutrients by the microalgae Chlorella vulgaris, using urban wastewater as culture medium, namely the effluent subjected to secondary biological treatment in a wastewater treatment plant (WWTP). For this, laboratory experiments were performed in batch cultures to study the effect of initial nitrogen and phosphorus concentrations on growth and reduction of nutrient performance of C. vulgaris. The microalga was cultivated in enriched wastewater containing different phosphorus (1.3-143.5 mg x L(-1) P.PO4(3 )), ammonium (5.8-226.8 mg x L(-1) N-NH4+) and nitrate (1.5-198.3 mg x L(-1) N NO3-) concentrations. The nutrient removal and growth kinetics have been studied: maximum productivity of 0.95 g SS x L(-1) x day(-1), minimum yield factor for cells on substrate (Y) of 11.51 g cells x g nitrogen(-1) and 0.04 g cells x g phosphorus(-1) were observed. The results suggested that C. vulgaris has a high potential to reduce nutrients in secondary WWTP effluents. PMID- 21972512 TI - Effects of soil amendments and EDTA on lead uptake by Chromolaena odorata: greenhouse and field trial experiments. AB - Greenhouse and field trial experiments were performed to evaluate the use of Chromolaena odorata with various soil amendments for phytoextraction of Pb contaminated soil Pb mine soils contain low amount of nutrients, so the additions of organic (cow manure) and inorganic (Osmocote and NH4NO3 and KCl) fertilizers with EDTA were used to enhance plant growth and Pb accumulation. Greenhouse study showed that cow manure decreased available Pb concentrations and resulted in the highest Pb concentration in roots (4660 mg kg(-1)) and shoots (389.2 mg kg(-1)). EDTA increased Pb accumulation in shoots (17-fold) and roots (11-fold) in plants grown in soil with Osmocote with Pb uptake up to 203.5 mg plant(-1). Application of all fertilizers had no significant effects on relative growth rates of C. odorata. Field trial study showed that C. odorata grown in soil with 99545 mg kg( 1) total Pb accumulated up to 3730.2 and 6698.2 mg kg(-1) in shoots and roots, respectively, with the highest phytoextraction coefficient (1.25) and translocation factor (1.18). These results indicated that C. odorata could be used for phytoextraction of Pb contaminated soil. In addition, more effective Pb accumulation could be enhanced by Osmocote fertilizer. However, the use of EDTA in the field should be concerned with their leaching problems. PMID- 21972513 TI - Phytoremediation potential of Pityrogramma calomelanos var. austroamericana and Pteris vittata L. grown at a highly variable arsenic contaminated site. AB - This study examined the phytoextraction potential of two arsenic (As) hyperaccumulators, Pteris vittata L. and Pityrogramma calomelanos var. austroamericana at a historical As-contaminated cattle dip site in northern New South Wales (NSW), Australia. Total As concentration in the surface soil (0-20 cm) showed a better spatial structure than phosphate-extractable As in the surface and sub-surface soil at this site. P. calomelanos var. austroamericana produced greater frond dry biomass (mean = 130 g plant(-1)) than P. vittata (mean = 81 g plant(-1)) after 10 months of growth. Arsenic concentration and uptake in fronds were also significantly higher in P. calomelanos var. austroamericana (means = 887 mg kg(-1) and 124 mg plant(-1)) than in P. vittata (means = 674 mg kg(-1) and 57 mg plant(-1)). Our results showed that under the field conditions and highly variable soil As at the site, P. calomelanos var. austroamericana performed better than P. vittata. We predict that P. calomelanos var. austroamericana would take approximately 100 years to reduce the total As to below 20 mg kg(-1) at the site compared to > or =200 years estimated for P. vittata. However, long-term data are required to confirm these observations under field conditions. PMID- 21972514 TI - Application of rhizosphere interaction of hyperaccumulator Noccaea caerulescens to remediate cadmium-contaminated agricultural soil. AB - There is an urgent requirement for selecting appropriate technologies to solve food safety problems due to soil contamination. In this study, the hyperaccumulator Noccaea caerulescens and a high Cd accumulator pakchoi cultivar (Brassica rapa L. spp. Chinenesis cv.) were grown in a moderately Cd-contaminated soil with three planting systems (monocrop, inter-crop, and crop-rotation) and three growing durations (25, 50, and 75 days) to study the role of rhizosphere interaction of both species on the uptake of Cd. The Cd accumulations in the shoot of pakchoi were significantly reduced in the inter-crop treatment, also the decreased percentage increased with rhizosphere interaction between the two species. In the inter-crop systems of 75 days, the Cd concentration and amount in the shoot of pakchoi represented 54% and 83% reduction, respectively, while the total depletion of Cd decreased by approximate 19%. Although the Cd concentration and amount in the shoot of pakchoi were significantly reduced by 52% and 44%, respectively, in the crop-rotation treatment, the decreased percentage were markedly lower than in the inter-crop treatment. Therefore, the rhizosphere interaction of hyperaccumulator with non-hyperaccumulator may reduce the risk of vegetable contamination during making full use of or remediating the contaminated soil. PMID- 21972515 TI - Lead uptake and translocation by willows in pot and field experiments. AB - Plant growth and lead (Pb) uptake by seven willow varieties were investigated in pot and field experiments to assess the suitability of willows for phytoremediation of Pb at heavily contaminated sites such as skeet ranges. Differences in uptake and translocation of Pb in Salix were observed between pot and field experiments. In the pot experiment, willows grown in Pb-contaminated field soil for 6 months showed tolerance to very high soil Pb concentration (21,360 mg kg(-1)), and with the addition of EDTA were able to take up and translocate more than 1000 mg kg(-1) Pb into above-ground tissues. In the field experiment, all willow varieties showed tolerance to heterogeneously high soil Pb concentrations. Plants were also able to take up and translocate Pb into above ground tissues. However, after 4.5 months, the lead concentration in the above ground tissues of willows grown in soil amended with EDTA was less than 200 mg kg(-1). The results from the pot experiment suggest that Salix varieties have the potential to take up and translocate significant amounts of Pb into above-ground tissues using EDTA. However, to verify the phytoextraction abilities of Salix in the field, additional research is needed. PMID- 21972516 TI - Rhizosphere concentrations of zinc and cadmium in a metal contaminated soil after repeated phytoextraction by Sedum plumbizincicola. AB - A growth chamber pot experiment and a field plot experiment were conducted with the installation of rhizobags to study the effects of repeated phytoextraction by Sedum plumbizincicola on the bioavailability of Cd and Zn in the rhizosphere and bulk soil Repeated phytoextraction gave significantly lower Cd and Zn concentrations in both rhizosphere and bulk soil solutions compared with soil without repeated phytoextraction. The depletion rates of NH40Ac-extractable Zn in rhizosphere soil in each treatment (L-PS, L-NPS, H-PS, and H-NPS) were 59.7, 18.0, 16.3, and 18.6%, respectively. For NH40Ac-extractable Cd, the depletion rates in treatments L-PS, L-NPS, H-PS, and H-NPS were 6.67, 29.4, 40.3, and 41.4%, respectively. Plant shoot biomass decreased in the order H-PS > H-NPS > L PS > L-NPS, with dry weights of 0.56, 0.42, 1.43, and 1.21 g pot(-1), respectively. Plant Cd uptake increased with increasing aqua-regia extractable metal concentrations. The NH4OAc extraction procedure was satisfactory to predict the bioavailability of Cd and Zn in rhizosphere soil in terms of shoot uptake by S. plumbizincicola with positive correlation coefficients of 0.545 (p < 0.05) and 0.452 (p < 0.05), respectively. The field study results show a slight decrease in water soluble and NH4OAc-extractable metals, a trend similar to that found in the pot experiment. PMID- 21972517 TI - Potential cultivation of Hordeum vulgare L. in soils with high mercury background concentrations. AB - Experimental work was carried out under close-to-real conditions to study mercury uptake by Hordeum vulgare L. cultivated in lysimeter experiments. The soil in the lysimeter experiment was obtained from a test plot located near Almaden (Spain) and had a mean mercury content of 22.9 mg kg(-1). A sequence of four crops was sown starting in autumn 2000 and repeated on a yearly basis until 2004. The first crop was grown in the field prior to the extraction of 5 one-cubic-meter lysimeters. The succeeding crops were sown in the lysimeter experiments at the CIEMAT Research Centre (Madrid, Spain). Samples of root and shoot were obtained during the four seasons. Concentrations of mercury at plant maturity in roots vary between I and 3 mg kg(-1) and in straw and grain the concentrations range from 72 to 480 microg kg(-1) and from 5 to 257 microg kg(-1), respectively. In order to assess the potential risk for human health and animal feed, an evaluation of the mercury content in the edible part of the crop has been carried out. According to legislation, there is no human health intoxication risk with a balanced consumption; otherwise, the forage use would have to be controlled. PMID- 21972518 TI - Assessment of bioaccumulation of heavy metal by Pteris vittata L. growing in the vicinity of fly ash. AB - Pteris vittata L. subsp. vittata, a potential arsenic hyperaccumulator fern, growing naturally in the vicinity offly ash was analyzed for the concentration of nine heavy metals (Fe, Cu, Zn Ni, Al, Cr, Pb, Si, and As) from five different sites around of Kanti Thermal Power Station at Muzaffarpur in Bihar State, India. Metal accumulation in P. vittata was correlated with the level of pollution at five selected sampling sites. The results revealed significantly more accumulation of these metals in the above ground parts of the plant than the parts below ground. Statistical parameters such as the coefficient of variation (CV%) showed a higher for As, Cu, Cr, and a lower one for Fe, Ni, Al. There was high spatial variability in the total metal concentration at different sites. The present study confirmed that P. vittata is a heavy metals accumulator and that it is a highly suitable candidate for phytoremediation of metal contaminated wastelands. PMID- 21972519 TI - Phytostabilization potential of Jatropha curcas L. in polymetallic acid mine tailings. AB - Greenhouse pot experiments were conducted to determine the growth response, metal tolerance, and phytostabilization potential of Jatropha curcas L The plants were grown on different degrees of multi-metal contaminated acid mine soils (T0, control; T1, moderately and T2, highly contaminated soils) with or without limestone amendments. The order of metal accumulation in J. curcas was roots>stems>leaves. The higher tolerance index (>90%) with no phytotoxic symptoms and growth reduction in T1 showed that this plant has the ability to tolerate polymetallic acid mine tailings. Further, various enzymatic and non-enzymatic antioxidants also actively involved in metal defense mechanism in J. curcas. On the other hand, to alleviate the predominant phytoavailable toxic metals such as Al, Cu, and Pb, different rates (0.1, 0.25, 0.50, and 1%) of limestone amendments were added in both T1 and T2 soils. The growth performance of J. curcas was improved due to the increase in soil pH and decrease in phytoavailable soil A1 (95%), Zn (approximately 75%), and Cu (approximately 65%) contents at 0.50% of lime addition. Based on the inherent tolerance ability of J. curcas in existing adverse environmental conditions without liming, it could be used as a suitable candidate for phytostabilization in acid mine tailings. PMID- 21972520 TI - Nickel-induced changes in lipid peroxidation, antioxidative enzymes, and metal accumulation in Lemna gibba. AB - In this study, an experiment was carried out to study the process of stress adaptation in Lemna gibba grown under nickel stress (0-20 mg Ni L(-1)). The results showed that Ni concentrations in plants increased with increasing Ni supply levels and reached a maximum of 142.82 mg.kg1 DW at 0.5 mg x L(-1) Ni treatments. The level of photosynthetic pigments (Chl a, Chi b, and total Chl) and soluble proteins increased upon exposure to high Ni concentrations. At the same time, the level of malondialdehyde (MDA) increased with increasing Ni concentration. These results suggested an alleviation of stress that was presumably the results of antioxidants such as superoxide dismutase (SOD), catalase (CAT) which generally increased linearly with increasing Ni levels. In addition, the proline content in L. gibba increased with increasing nickel levels. Our present work concluded that Lemna gibba has a high level of nickel tolerance and accumulation. We also found that moderate nickel treatment (0.05-5 mg x L(-1)) alleviated oxidative stress in plants, while the addition of higher amounts of nickel (10-20 mg x L(-1)) could cause an increasing generation of ROS, which was effectively scavenged by the antioxidative system. Therefore, L. gibba may be used as a phytoremediator in moderately polluted aquatic ecosystems. PMID- 21972521 TI - Chemical-assisted phytoremediation of CD-PAHs contaminated soils using Solanum nigrum L. AB - A well-characterized cadmium (Cd) hyperaccumulating plant Solanum nigrum was grown in Cd and polycyclic aromatic hydrocarbons (PAHs) co-contaminated soil that was repeatedly amended with chemicals, including EDTA, cysteine (CY), salicylic acid (Sa), and Tween 80 (TW80), to test individual and combined treatment effects on phytoremediation of Cd-PAHs contaminated soils. Plant growth was negatively affected by exogenous chemicals except for EDTA. S. nigrum could accumulate Cd in tissues without assistant chemicals, while there was no visible effect on the degradation of PAHs. Cysteine had significant effects on phytoextraction of Cd and the highest metal extraction ratio (1.27%) was observed in 0.9 mmol/kg CY treatment. Both salicylic acid and Tween 80 had stimulative effects on the degradation of PAHs and there was the maximal degradation rate (52.6%) of total PAHs while 0.9 mmol/kg Sa was applied. Furthermore, the combined treatment T(0.1EDTA+0.9CY+0.5TW80) and T(0.5EDTA+0.9CY+03Sa) could not only increase the accumulation of Cd in plant tissues, but also promote the degradation of PAHs. These results indicated that S. nigrum might be effective in phytoextracting Cd and enhancing the biodegradation of PAHs in the co-contaminated soils with assistant chemicals. PMID- 21972522 TI - Effects of arsenate (AS5+) on growth and production of glutathione (GSH) and phytochelatins (PCS) in Chlorella vulgaris. AB - The effect of arsenate (As5+) on growth and chlorophyll a production in Chlorella vulgaris, its removal by C. vulgaris and the role of glutathione (GSH) and phytochelatins (PCs) were investigated. C. vulgaris was tolerant to As5+ at up to 200 mg/L and was capable of consistently removing around 70% of the As5+ present in growth media over a wide range of exposure concentrations. Spectral analysis revealed that PCs and their arsenic-combined complexes were absent, indicating that the high bioaccumulation and tolerance to arsenic observed was not due to intracellular chelation. In contrast, GSH was found in all samples ranging from 0.8 mg/L in the control to 6.5 mg/L in media containing 200 mg/L As5+ suggesting that GSH plays a more prominent role in the detoxification of As5+ in C. vulgaris than PC. At concentrations below 100 mg/L cell surface binding and other mechanisms may play the primary role in As5+ detoxification, whereas above this concentration As5+ begins to accumulate inside the algal cells and activates a number of intracellular cell defense mechanisms, such as increased production of GSH. The overall findings complement field studies which suggest C. vulgaris as an increasingly promising low cost As phytoremediation method for developing countries. PMID- 21972523 TI - [Effects of multiwall carbon nano-onions on platelet aggregation and hemostatic function]. AB - OBJECTIVE: To observe the effects of multiwall carbon nano-onions (MWCNOs) on platelet aggregation and hemostatic function. METHODS: The platelet aggregation was determined with Born's method at different concentration of MWCNOs (0, 0.2, 2.0, 20.0 microg/ml) in vitro. Twenty male SD rats were randomly divided into 4 groups which were exposed to 0, 2, 4 and 8 mg/kg MWCNOs, respectively. Then platelet count, platelet aggregation, activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), bleeding time (BT) and platelet count (PC) were measured at 12 h after receiving tail intravenous injection of MWCNOs. The effects of MWCNOs (4 mg/kg) on platelet aggregation and platelet count at different time points were observed. RESULTS: In vitro, MWCNOs exhibited the potent inhibitory effects on rat platelet aggregation caused by ADP in a concentration-dependent manner. The platelet aggregation in the highest dosage of 20.0 microg/ml group was 50.0% +/- 6.9% which was significantly lower than that (73.2% +/- 4.3%) in control group (P<0.01). In vivo, the highest inhibitory was up to 20.4%, but there was no significant difference, as compared with control group. MWCNOs did not affect the APTT, PT, TT, BT and PC. CONCLUSION: Under this experimental condition, MWCNOs might inhibit platelet aggregation but not affect hemostatic function. PMID- 21972524 TI - [The study of susceptibility to carbon tetrachloride and benzene in offspring of expanded simple tandem repeats mutation mice exposed to formaldehyde]. AB - OBJECTIVE: To investigate the susceptibility to carbon tetrachloride and benzene in offspring of expanded simple tandem repeats (ESTR) mutation mice exposed to formaldehyde (FA). METHODS: F5 and F10 offspring (200 mg/m3 x 2 hours) served as H group and ICR mice were used as control group (group C). The F5 and F10 offspring were exposed to 10 ml/kg carbon tetrachloride at the doses of 0.05%, 0.50% or 5.00% for 24 hours, respectively or 500 or 1000 mg/kg benzene for 24 hours, respectively by intraperitoneal injection. Serum alanine transaminase (ALT), aspartate transaminase (AST) and the hepatic superoxide dismutase (SOD) or malondialdehyde (MDA) were detected; also the hepatic pathological changes were observed under light microscope; the micronucleus in sternum bone marrow cells as the biomarker of benzene blood toxicity were measured. RESULTS: ALT and AST activities in group C of F5 mice exposed to 0.50% and 5.00% CCl4, ALT in groups C and H of F10 mice exposed to 0.05%, 0.50%, 5.00% CCl4, AST in groups C and H of F10 mice exposed to 0.50% and 5.00% CCl4 were significantly higher than those in controls, respectively (P<0.05); as compared to the control, hepatic SOD activities in group C of F5 and F10 mice exposed to 0.50% and 5.00% CCl4, in group H of F5 mice exposed to 0.50% and 5.00% CCl4 and F10 mice exposed to 5.00% CCl4 were significantly reduced, respectively (P<0.05); however, MDA contents in group C of F10 mice exposed to 0.50% and 5.00% CCl4, in group H of F5 mice exposed to 0.05% and 0.50%, 5.00% CCl4 and F10 mice exposed to 0.50% and 5.00% CCl4 were significantly increased than those in control group, respectively (P<0.05). The susceptibility to CCl4 in ESTR mutation F5 mice exposed to FA was significantly higher than that in control F5 mice, but the susceptibility to CCl4 in ESTR mutation F10 mice exposed to FA was significantly lower than that in control F10 mice. The histopathological examination showed that the injury of hepatocytes in C and H groups significantly increased CCl4 doses, and the injury of hepatocytes in H group was higher than that in C group. The micronuclear rates in C and H group mice exposed to benzene(500 mg/kg C group, F5 and F10 mice; 1000 mg/kg C group, F5 and F10 mice; 500 mg/kg H group, F5 and F10 mice; 1000 mg/kg C group, F5 and F10 mice) were 5.88 per thousand +/- 4.55 per thousand, 8.25 per thousand +/- 2.06 per thousand, 7.50 per thousand +/- 6.99 per thousand, 10.67 per thousand +/- 1.16 per thousand, 7.88 per thousand +/- 3.09 per thousand, 9.20 per thousand +/- 1.30 per thousand, 9.63 per thousand +/- 4.34 per thousand and 13.33 per thousand +/- 2.08 per thousand, respectively, which were significantly higher than those (1.13 per thousand +/- 0.35 per thousand, 1.20 per thousand +/- 0.82 per thousand, 1.25 per thousand +/- 0.46 per thousand, 1.33 per thousand +/- 1.03 per thousand) in the solvent control group (P<0.05 or P<0.01). CONCLUSION: FA could result in the change of susceptibility to CCl4 and benzene in offspring of ESTR mutation mice. ESTR mutation may be a biomarker of the susceptibility to chemicals, but the molecular mechanisms should be investigated in the future. PMID- 21972525 TI - [The roles of Ku80/p53 pathway in silica-induced cell cycle changes in human embryo lung fibroblasts]. AB - OBJECTIVE: To study the roles of Ku80/p53 pathway in silica-induced cell cycle changes in human embryo lung fibroblasts (HELF). METHODS: Ku80 siRNA expression vectors were transfected into HELF by lipofectamine. Flow cytometry was used to detect the distributions of cell cycle and western blot assay was used to determine the expression level of Ku80, p53 and p21 proteins or the phosphorylation levels of p53-ser15 after cells were exposed to silica. RESULTS: The expression levels of Ku80 protein increased in concentration-dependent and time-dependent manners after cells were exposed to silica. The proportion of G1 phases in H-NC cells (controls) decreased from 89.28% +/- 2.19% to 68.93% +/- 3.79% after exposure to silica, and the proportion of G1 phases in HELF cells (H Ku80) decreased from 85.16% +/- 3.73% to 59.92% +/- 3.31% after exposure to silica (P<0.05). The expression levels of Ku80, p53 proteins or p21 proteins or phosphorylation level of p53-ser15 were obviously suppressed in H-Ku80, as compared with H-NC. CONCLUSION: Ku80/p53 pathway plays a role in the cell cycle charges induced by silica in human embryo lung fibroblasts. PMID- 21972526 TI - [Effect of phosphatidylinositol 3-kinase/serine-threonine kinase signalling pathway during the proliferation process of HL-60 cells exposed to benzoquinone]. AB - OBJECTIVE: To explore the effects of phosphatidylinositol 3-kinase/Serine threonine kinase (PI3K/Akt) signal pathway on the proliferation of HL-60 cells exposed to benzoquinone (BQ). METHODS: HL60 cells were divided into 3 groups: control group (treated with PBS), BQ group (treated with 3 micromol/L BQ) and LY294002 plus BQ group (treated with 20 micromol/L LY294002 plus 3 micromol/L BQ). The cell proliferation was measured with alamar blue dye assay. Western blot assay was used to detect the expression of p-Akt and Akt proteins and flow cytometer was used to observe the cell cycle. RESULTS: The cell proliferation rate and the cell proportion in the S, G2 phase of BQ group were 185.00% +/- 30.00%, 48.23% +/- 1.37% and 15.40% +/- 1.21%, respectively, which were significantly higher than those (100.00% +/- 0.00%, 42.47% +/- 0.45% and 5.40% +/ 0.40%) of control group (P<0.05). But the cell proportion rate (36.37% +/- 0.40%) in the G1 phase in BQ group was significantly lower than that (52.13 +/- 0.75%) in control group (P<0.05). The expression level of p-Akt protein in BQ group was significantly higher than that in control group (P<0.05). The cell proliferation rate and the cell proportion in the S, G2 phase of LY294002 plus BQ group were 82.59% +/- 15.00%, 42.03% +/- 0.50% and 3.87% +/- 0.47%, respectively, which were significantly lower than those of BQ group (P<0.05). But the cell proportion rate (54.43% +/- 0.40%) in the G1 phase in LY294002 plus BQ group was significantly higher than that in BQ group (P<0.05). CONCLUSION: The PI3K/Akt signal pathway may play an important role in the proliferation of HL-60 cells exposed to BQ. PMID- 21972527 TI - [Effect of oxygen therapy on the morphology of cardiac muscle, lung and liver in rats with acute hydrogen sulfide intoxication]. AB - OBJECTIVE: To evaluate the effects of different oxygen therapy technique (different concentrations of normobaric oxygen and the hyperbaric oxygen) on the ultrastructure of cardiac muscle, lung and liver in rats with acute hydrogen sulfide intoxication. METHODS: One hundred healthy male Wistar rats were randomly divided into five groups: normal control group (A), poisoned group (B), oxygen therapy group (C), oxygen therapy group (D) and oxygen therapy group (E). After the exposure to 300 ppm H2S for 60 min in a static exposure tank (1 m3), the rats were treated with oxygen therapy, C, D and E groups were given 33% oxygen, 50% oxygen of atmospheric oxygen and hyperbaric oxygen therapy for 100 min, respectively. The rats in normal control group inhaled air under the same environment. After exposure and therapy, the tissues of lung, heart and liver were observed under light microscope and electron microscope. RESULTS: The results of light microscope examination showed that the broken and not well aligned cardiac myofilaments, cytoplasmic edema and pyknosis could be seen in group B. The well aligned and clear cardiac myofilaments appeared in group C, D and E. The alveolar hemorrhage, edema and inflammatory cells exudation could not be seen in group A. Alveolar epithelial cell edema, unsmooth alveolar edge and alveolar inflammatory cells exudation could be found in group B. The unsmooth alveolar septal borders and pulmonary edema could be seen occasionally in group C and D, the alveolar inflammatory cells exudation could not be seen in group E. The regular hepatic boards and the uniform hepatic cellular nuclei were found in group A. The disordered hepatic boards, widened cellular gaps and cytoplasmic edema could be seen occasionally in group B. The irregular hepatic boards and ballooning degeneration could be seen in group C and D. The regular hepatic boards and uniform cytoplasm could be found in group E. The results of electron microscope examination indicated that the mitochondrial swelling, autolyzing, fuzzy and breakage of myocardial cells were observed in group B; the clear mitochondrial structure appeared in group E. The apoptosis and organelle vacuole of alveolar epithelial cells could be observed in group B. The relatively normal nuclei of alveolar epithelial cells could be seen in group E. The lax cytoplast structure of hepatocytes, unclear nuclear membrane, lumped chromatin, slightly swelled mitochondria and phagosomes were observed in group B. However, no improved change was observed in group C, D and E. CONCLUSION: Hydrogen sulfide could induce the extensive and severe damage of myocardial mitochondria, alveolar epithelial cells and hepatocytes, the oxygen therapy in good time could reduce significantly the myocardial injury, and improve the lung injury to some extent. High-pressure oxygen therapy is better than the normobaric oxygen therapy. PMID- 21972528 TI - [The effects of caspase-3 siRNA on the neurobehavior of mice exposed to aluminum]. AB - OBJECTIVE: To investigate the effects of caspase-3 siRNA on the neurobehavior of mice exposed to aluminum. METHODS: Male KunMing mice (3 months old) were randomly divided into 4 groups by weight:blank control group (4 microl normal saline), Al group (4 microl 0.5% AlCl3), Al plus empty vector group(3 microl 0.5% AlCl3 plus control siRNA expression vector)and Al plus RNAi group (3 microl 0.5% AlCl3 plus targeted siRNA expression vector). All groups were treated by lateral cerebral ventricle micro-injection for 5 days. The neurobehavior was tested by the Morris water maze test, Open-field and Step-down tests for all treated mice. Pathological changes in hippocampus was observed by electron microscopy, the caspase-3 gene expression levels were detected using RT-PCR. RESULTS: The results of Step-down test indicated that as compared with control group, the latent time [LT, (44.67 +/- 10.60) s] in A1 group decreased significantly, the error number (3.63 +/- 0.52) in Al group increased significantly and the LT [(68.00 +/- 14.70) s] in Al plus empty vector group decreased significantly (P<0.05). the LT [(239.50 +/- 19.36) s] in Al plus RNAi group increased significantly and the error number in Al plus RNAi group decreased significantly, as compared with Al group (P<0.05). The results of Morris water maze test showed that as compared with control group, the LT in Al group increased significantly, and residence time in the former platform quadrant decreased significantly and the LT in Al plus empty vector group increased significantly (P<0.05). The LT in Al plus RNAi group was significantly longer than that in Al group (P<0.05). The results of open-field test demonstrated that as compared with control group, the time in the central grid in Al group and Al plus empty vector group increased significantly, the rearing number and the modification number in Al group and Al plus empty vector group decreased significantly (P< 0.05). As compared with Al group, the time in the central grid in Al plus RNAi group decreased, the inter-cell number, the rearing number and the modification number increased significantly (P<0.05). The results of electron microscopic examination exhibited that a slight change of hippocampal cells appeared in control group, the obvious pathological changes of hippocampal cells appeared in Al group and Al plus empty vector group, but the pathological changes of hippocampal cells in Al plus RNAi group significantly reduced as compared with Al group. The results of thionin staining indicated that the layers of neural cells of hippocampal CA3 were more clear and there was not obvious denatured injury of neural cells of hippocampal CA3 in control group. The number and Nissl body color of neural cells of hippocampal CA3 in Al group and Al plus empty vector group decreased significantly. After RNA interference, the number and Nissl body color of neural cells of hippocampal CA3 increased obviously. The expression levels of caspase-3 gene in Al group and Al plus empty vector group were 2.24 +/- 0.57 and 2.28 +/- 0.33, respectively, which were significantly higher than that (1.00 +/- 0.00) in control group (P<0.05). The expression level of caspase-3 gene in Al plus RNAi group was 0.44 +/- 0.08, which was significantly lower than those in Al group and control group (P<0.05). CONCLUSION: Aluminum can decrease the learning and memorizing ability, and inhibited the activity or exploration function of mice. It is suggested that Caspase-3 siRNA may reduce the neurotoxicity induced by aluminum to a certain extent. PMID- 21972529 TI - [Six cases of occupational acute 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride poisoning]. PMID- 21972530 TI - [Effects of overexpression of heat shock protein 70 on the damage induced by formaldehyde in vitro]. AB - OBJECTIVE: To investigate the protective role of inducible heat shock protein 70 (Hsp70) against damage induced by formaldehyde. METHODS: Human bronchial epithelium (HBE) cells were transfected with plasmid harboring hsp70 gene to increase the protein expression level. HBE cells transfected with pcDNA3.1 plasmid were used as transfection control and HBE cells cultured at normal condition served as control. Three groups were marked as HBE/hsp70, HBE/pcDNA and HBE. Hsp70 expression levels of 3 groups were detected. The cells of HBE/hsp70 and HBE groups were exposed to different concentrations of formaldehyde (0,0.39,1.56,6.25 mmol/L) for 4 h. The contents of GSH and MDA were measured, and KCl-SDS method was applied to measure DNA-protein crosslink (DPC). RESULTS: Hsp70 level in HBE/hsp70 group increased by 80% compared with HBE group. GSH contents in HBE/hsp70 group significantly increased and were 141.0, 119.6 mg/gpro at 0.39, 1.56 mmol/L, respectively (P<0.01), as compared with HBE group. However, it decreased when formaldehyde concentration increased to 6.25 mmol/L. While GSH content in HBE group remained decreasing. MDA contents in HBE/hsp70 and HBE group increased with formaldehyde. MDA content in HBE/hsp70 was 0.088 micromol/gpro and significantly lower than that (0.138 micromol/gpro) in HBE group (P<0.05) when formaldehyde concentration was 1.56 mmol/L, At the formaldehyde dose of 6.25 mmol/L MDA content in HBE/hsp70 was 0.140 micromol/gpro which was significantly lower than that (0.289 micromol/gpro) in HBE group (P<0.01). DPC% in two groups increased with formaldehyde. At the formaldehyde dose of 0.39 mmol/L, DPC% in HBE/hsp70 group was 3.94% which was significantly lower than that (6.25%) in HBE group (P< 0.01). At the formaldehyde dose of 1.56 mmol/L, DPC% in HBE/hsp70 group was 11.86% which was significantly lower than that (20.89%) in HBE group (P<0.05). CONCLUSION: Hsp70 can reduce formaldehyde-induced damages in human bronchial epithelium cells in vitro. PMID- 21972531 TI - [Study on factors affecting the quality of life for nurses working in night shifts]. AB - OBJECTIVE: To explore the situation of quality of life (QOL) of nurses working in night shifts and the major factors influencing the QOL, and to provide scientific basis of the further effective intervention for the quality of life. METHODS: The nurses working in night shift were sampled randomly in Grade 3A-hospitals of Tianjin, and investigated using WHO Quality of Life-BREF Scale. RESULTS: Three hundred eighty five questionnaires were collected from 398 questionnaires. The average score of subjective QOL perception was 2.90 (the full score is 5), subjective health perception was 2.64 (the full score is 5). The score of physical domain of QOL was 13.21 +/- 2.18; psychological domain of QOL was 13.38 +/- 2.28; social domain of QOL was 14.71 +/- 2.32; environmental domain of QOL was 11.36 +/- 2.31, all of which were significantly lower than norm value (P<0.01). The results analyzed by ordinal logistic regression showed that the factors affecting physical domain of QOL were years of working experience, sleep time, gastrointestinal disorders, family harmony status and regular diet; the factors affecting psychological domain of QOL were family harmony status and gastrointestinal disorders; the factors affecting social domain of QOL were the nature of nursing work and family harmony status; the factors affecting environmental domain of QOL were job title, sleep time, gastrointestinal disorders and regular diet. CONCLUSION: The QOL of nurses working in night shifts is lower than that of general people. The corresponding measures should be taken to raise the quality of life of nurses in night shifts. PMID- 21972532 TI - [Analysis of new pneumoconiosis cases during 2006-2009 in Zhejiang province]. AB - OBJECTIVE: To analyze the characteristics of pneumoconiosis cases in Zhejiang province and to provide the evidence for pneumoconiosis control and prevention measures in Zhejiang province. METHODS: The data of new pneumoconiosis cases were from national surveillance system of occupational disease in Zhejiang province during 2006-2009, and were analyzed for distribution, age, exposure duration, pneumoconiosis phases and enterprise types. RESULTS: During 2006-2009, 819 new pneumoconiosis cases (173, 157, 209 and 280 cases, respectively) were reported, 86.9% cases suffered from silicosis. Most of pneumoconiosis cases were distributed in Ningbo, Wenzhou areas and in building materials, machinery, coal, geological and mining, light industries and construction enterprise. The average ages of new pneumoconiosis cases were (47.8 +/- 10.0), (52.5 +/- 13.1), (55.5 +/- 11.2) and (55.9 +/- 12.2) years old, respectively and showed a significant increase trend (P<0.05). The average exposure duration of new pneumoconiosis cases were (12.4 +/- 8.6), (12.9 +/- 9.4), (12.4 +/- 8.6) and (15.7 +/- 10.0) years. The average exposure duration of phase I, phase II, phase III new pneumoconiosis cases were (14.3 +/- 9.87), (12.4 +/- 8.7) and (11.4 +/- 7.1) years, respectively and there were significant differences (P<0.05). CONCLUSION: New pneumoconiosis cases in Zhejiang province are increasing year by year, the main type of pneumoconiosis is silicosis, the distribution of pneumoconiosis cases is associated with the areas and enterprises, and the exposure duration of new pneumoconiosis cases is relatively shorter. PMID- 21972533 TI - [Evaluating the effects of different oxygen therapies on the rats with acute nitrogen asphyxia]. AB - OBJECTIVE: To Evaluate the effects of different oxygen therapies on the rats with acute nitrogen asphyxia and to study the best oxygen therapic protocol for patients with acute nitrogen asphyxia on the spot. METHODS: Sixty healthy male Wistar rats were divided into 5 groups: control, exposure to nitrogen, 33% oxygen treatment, 50% oxygen treatment and hyperbaric oxygen treatment groups. The behavioral performance, arterial oxygen pressure (PO2), carbon dioxide partial pressure (PCO2) and oxygen saturation (SPO2), biochemical changes in liver and kidney function and myocardial enzymes in 5 groups were measured. RESULTS: The rats exposed to nitrogen firstly were excited then inactive symptoms, but consciousness was recovered after oxygen therapy. The PO2 and SPO2 in nitrogen exposure group were (79.67 +/- 9.12) and (94.92 +/- 2.78) mm Hg, respectively, which were significantly lower than those in control group (P<0.01). The PO2 and SPO2 of 3 oxygen treatment groups were (94.75 +/- 7.24), (94.92 +/- 8.98), (104.58 +/- 7.12)mm Hg and (97.17 +/- 0.83), (96.92 +/- 1.16), (97.42 +/- 0.67)mm Hg, respectively, which were significantly higher than those in nitrogen exposure group (P<0.05). The PO2 in hyperbaric oxygen treatment group was significantly higher than those in other 2 oxygen treatment groups (P<0.05). The SPO2 in hyperbaric oxygen treatment group was (51.42 +/- 6.60) mm Hg which was significantly higher than that [(44.58 +/- 3.42)mm Hg] in 50% oxygen treatment groups (P< 0.05). AST [(270.50 +/- 49.05 )U/L], ALT [(122.67 +/- 55.44 )U/L], BUN [(7.31 +/- 0.93 )mmol/L], Cr[(28.32 +/- 4.35) micromol/L], CK [(1808.42 +/- 582.05)U/L] and CtnI [(22.52 +/- 14.29 )ng/ml] in nitrogen exposure group were significantly higher than those in control group (P<0.05). AST [(165.25 +/- 30.87) U/L], HBDH [(350.83 +/- 103.00)U/L] and CtnI [(11.23 +/- 5.38) ng/ml] in hyperbaric oxygen treatment group were significantly lower than those in other 2 oxygen treatment groups (P<0.05). CONCLUSION: Timely and effective oxygen therapy can significantly increase arterial pressure of oxygen and oxygen saturation in the rats with acute nitrogen asphyxia, and can improve liver function and cardiac damage. The hyperbaric oxygen chamber can significantly increase the therapeutic effects on rats with acute nitrogen asphyxiation. PMID- 21972534 TI - [Screening the proteins of organophosphoms ester-induced delayed neurotoxicity in the cerebral tissue of hens exposed to tri-ortho-cresyl phosphate]. AB - OBJECTIVE: To screen the proteins with differential expression levels in the cerebral tissue of hens exposed to tri-ortho-cresyl phosphate (TOCP), and to provide target proteins for studying the mechanism of organophosphoms ester induced delayed neurotoxicity (OPIDN). METHODS: Thirty two adult Roman hens were randomly divided into four groups: TOCP group was exposed to 1000 mg/kg TOCP, PMSF group was exposed to 40 mg/kg PMSF, PMSF plus TOCP group was exposed to 40 mg/kg PMSF and after 24 h exposed to 1000 mg/kg TOCP, control group was exposed to normal saline. All hens exposed to chemicals by gastro-intestine for 5 days were sacrificed, and the cerebral tissue were dissected and homogenized in ice bath. Total proteins extracted from the cerebral tissue were separated by isoelectric focusing as the first dimension and SDS-PAGE as the second dimension. The 2-DE maps were visualized after silver staining and analyzed by Image Master 2D software. At last ,the expressed protein spots were identified by Mass spectrometry. RESULTS: From total proteins in TOCP group, the PMSF plus TOCP group and PMSF group, 1185, 1294 and 1063 spots were detected, respectively. One thousand three hundred thirty two spots from total proteins in control group were detected. The match rates of protein spots in TOCP group, the PMSF plus TOCP group and PMSF group were 78.32 %, 79.56 % and 80.93%, respectively. There were 235 protein spots with differential expression levels between TOCP group and control group, which included 158 up regulation spots and 77 down regulation spots. According to the PMSF features, there were 102 spots with differential expression levels between TOCP group and control group and without differential expression levels between TOCP group and PMSF plus TOCP group, among them there were 13 spots with 4 fold differential expression levels between TOCP group and control group and without differential expression levels between TOCP group and PMSF group. Seven protein spots (homer-1b, Destrin, heat shock protein 70, eukaryotic translation initiation factors, proteasome alpha1 subunit, lactate dehydrogenase B, glutamine synthetase) were detected by Mass spectrometry. CONCLUSION: There are 112 protein spots with differential expression levels of the cerebral tissue in TOCP group, which may be related to OPIDN, among them 13 protein spots with differential expression levels are associated closely with OPIDN. Seven protein spots detected by Mass spectrometry may be related to the mechanism induced by OPIDN. PMID- 21972535 TI - [The protective effects of Aduola Fuzhenglin on the heart injury induced by microwave exposure in rats]. AB - OBJECTIVE: To study the protective effects of AduoLa Fuzhenglin(ADL) on the heart injury induced by microwave exposure in rats. METHODS: One hundred forty male Wistar rats were divided randomly into 5 groups: control, microwave radiation, 0.75 g x kg(-1) d(-1) ADL, 1.50 g x kg(-1) d(-1) ADL and 3.00 g x kg(-1) d(-1) ADL pretreatment groups. Rats in three ADL pretreatment groups were administrated by ADL per day for 2w then exposed to 30 mW/cm2 microwaves for 15 min. The left ventricle blood of rats was obtained at 7 d and 14 d after exposure to microwaves, and the blood Ca2+, AST and CK were detected with Coulter automatic biochemical analyzer, then the histological changes and ultrastructure of heart were observed under light and electron microscopes. RESULTS: At 7 d and 14 d after exposure to microwaves, the blood Ca2+, AST and CK concentrations significantly increased (P<0.05 or P<0.01) as compared with controls; Heart muscle fibers showed wavilness, endotheliocyte karyopyknosis, anachromasis; The mitochondria swelling and cavitation, intercalary dies blurred in radiation groups. The changes in 0.75 g x kg(-1) d(-1) ADL pretreatment group were similar to the radiation group, but in 1.50 g x kg(-1)d(-1) and 3.00 g x kg(-1) d(-1) ADL pretreatment groups, above indexes of rats significantly reduced as compared with microwaves group (P<0.05); also the blood Ca2+, AST, CK contents were significantly lower than those in microwave group (P<0.05); The heart showed a tendency to improve. CONCLUSION: Microwave radiation (30 mW/cm2) can cause the blood Ca2+, AST and CK turbulence, and heart injury in the histology and ultrastructure; ADL at the dosages of 1.50 g x kg(-1) d(-1) and 3.00 g x kg(-1) d(-1) has a protective effects on the heart injury induced by microwave in rats. PMID- 21972536 TI - [An epidemiological investigation of acute occupational hand injuries]. AB - OBJECTIVE: To study composition, distribution and causes of acute occupational hand injuries in Beijing Jishuitan Hospital. METHODS: From April 1st 2005 to September 30th 2005, all patients with acute hand injuries were investigated by questionnaire focusing on all related epidemiological elements. RESULTS: Two thousand six hundred fifty eight cases with acute hand injuries were about 17.3 % of patients with acute orthopedic injuries. Their mean age was (30.4 +/- 10.8) years old. The radio of males to females in cases with acute hand injuries was 57:1. The cutting and crushing injuries were the main causes of acute hand injuries. Most of cases with acute hand injuries were engaged in work related to machines. The acute hand injuries were mainly involved in index and middle figures of both hands, 94.9 % of acute hand injuries were opening, and 87.6% of acute hand injuries were involved in the deep tissues. CONCLUSION: Acute hand injuries are the common occupational severe injuries for young male workers. The acute hand injuries occur in patients engaged in work related to machines. The prevention of acute hand injuries should be emphasized. PMID- 21972537 TI - [A study of recompression treatment schedule for treating type I decompression illness with medical hyperbaric chamber pressurized]. AB - OBJECTIVE: To observe the therapic effects of the recompression treatment schedule D2 (breathing 100% oxygen at 0.12 MPa gauge pressure) on the type I decompression illness (DCI) by hyperbaric chamber pressurized with air. METHODS: The recompression treatment schedule D2 was from the decompression treatment tables of in Germany BGI690. Seven cases on work site group (work site group) and five cases in hospital (hospital group) were treated using recompression treatment. All cases suffered from type I DCI after normal decompression procedures from working in compressed air in tunnel construction. These patients were treated with basic schedule D2 or extended schedule D2 according to the symptoms of the cases responded to recompression therapy. RESULTS: In the work site group, the pains of joints, arms and legs were released quickly, the therapic effects appeared at (8.1 +/- 8.1) min, the cases were cured with a recompression therapy of basic schedule D2, the total mean time of treatment was (150 +/- 0.0) min. In the hospital group, the pains of joints, arms and legs disappeared slowly, the therapic effects appeared at (115.0 +/- 60.0) min, the cases were cured with a recompression therapy of extended schedule D2, the total mean time of treatment was (270.0 +/- 0.0) min, which was significantly longer than that in the work site group (P<0.01). CONCLUSIONS: The treatment pressure is 0.12 MPa(gauge pressure) in schedule D2 with medical hyperbaric chamber pressurized with air,which can be used for treatment of type I DCI, the curative effects in the work site group are better than those in the hospital group. PMID- 21972538 TI - [Application of the national diagnostic criteria of occupational mercury poisoning]. AB - OBJECTIVE: To investigate the clinical manifestation of patients with renal injury induced by chronic mercury intoxication and the application of the diagnostic criteria of occupational mercury poisoning. METHODS: The clinical data of 8 patients with chronic occupational mercury intoxication were analysed and evaluated. RESULTS: All the observed clinical signs of chronic mercury intoxication correspond with the items of the diagnostic criteria of occupational mercury poisoning. The increasing beta2-MG was one of the clinical manifestations of renal injury induced by chronical mercury intoxication. The renal injury obviously was dose-dependent and reversible. CONCLUSIONS: The national diagnostic criteria of occupational mercury poisoning is practically valuable. The renal injury induced by chronic mercury intoxication should not be neglected. PMID- 21972539 TI - [The comparison of clinical manifestation of organophosphorus pesticide poisoning (OPP) between oral exposure and occupational exposure in field work]. AB - OBJECTIVE: To investigate the differences of clinical manifestation and therapy of organophosphorus pesticide poisoning (OPP) between oral exposure and occupational exposure in field work. METHODS: From July 2007 to July 2010, 85 patients with acute severe OPP were treated in a hospital, which were divided into oral poisoning group (51 cases) and non-oral poisoning group (34 cases). The differences of clinical manifestations, curative effects and prognosis between two groups were compared. RESULTS: The rates of myoclonus and ataxia in cases with moderate poisoning of oral poisoning group were 86.4% and 90.9%, which were significantly higher than those (50.0% and 55.0%) of non-oral poisoning group (P<0.05 or P< 0.01). The rates of myoclonus, lung fluid and coma in cases with severe poisoning of oral poisoning group were 100.0%, 89.7% and 93.1%, respectively, which were significantly higher than those (71.4%, 64.3% and 50.0%) of non-oral poisoning group (P<0.05). The mean detoxification hours in cases with moderate poisoning and cases with severe poisoning of non-oral poisoning group were (35.0 +/- 6.2) and (45.0 +/- 11.1) hours which were significantly lower than those [(49.0 +/- 7.7) and (77.0 +/- 10.3) hours] in cases with moderate poisoning and cases with severe poisoning of oral poisoning group (P<0.05). In 24, 48 and 72 h after treatment, the cholinesterase (ChE) activities of non-oral poisoning group were higher than those of oral poisoning group (P< 0.05 or P<0.01). The used doses of pyraloxime methylchloride (PAM-Cl) or atropine and the used total dose of atropine in non-oral poisoning group were lower than those in oral poisoning group (P<0.05 or P<0.01). CONCLUSIONS: The clinical manifestation of non-oral poisoning group is different from the clinical manifestation of oral poisoning group due to the high morbidity of OPP occurred at field site in summer. The used doses of atropine and PAM-Cl are less and the ChE activity recovers quickly for non-oral poisoning group. PMID- 21972540 TI - [Electromagnetic hypersensitivity: current status and prospect]. PMID- 21972541 TI - [Use of fluorescence in situ hybridization in combination with the comet assay in DNA damage and repair]. PMID- 21972542 TI - [Progress in research on task-based measurement for noise]. PMID- 21972543 TI - [Clinical treatment of acute methanol poisoning]. PMID- 21972544 TI - [A case with a pseudo thrombocytopenia in workers occupationally exposed to benzene]. PMID- 21972545 TI - [One case of acute thallium poisoning]. PMID- 21972546 TI - [Analysis on 22 cases of urinary bladder carcinoma caused by benzidine in a certain dyestuff works]. PMID- 21972547 TI - [Two cases of occupational ethylene oxide poisoning]. PMID- 21972548 TI - [One case of occupational sodium azide poisoning]. PMID- 21972549 TI - [A case with acute sulfureted hydrogen poisoning treated by methylene blue]. PMID- 21972550 TI - [Analysis of the results of health examination for 2017 bus drivers or conductors in a city]. PMID- 21972551 TI - [Bioinformatics technologies for the analysis of antigenic evolution of influenza viruses]. AB - Human influenza viruses mutate from time to time, causing annual epidemics worldwide. The strong immune pressure in the human population selects a new variant every year, and the antigenic change is one of the primary reasons why vaccination is not a perfect measure to control seasonal influenza. Thus prediction of antigenic change of influenza A virus has been one of the major public health goals. In this review bioinformatics technologies that have been developed to achieve this goal were summarized. PMID- 21972552 TI - [Genome-wide association study on and the clinical application to chronic hepatitis C]. AB - Based on the data and technology generated in previous international projects, such as the Human Genome Project and the HapMap, for the building of the common patterns of genetic variation in humans, a genome-wide association study (GWAS) to HCV infection was conducted to reveal genetic effects against treatment response or the induction of side effects. Single nucleotide polymorphisms (SNPs) associated with response to pegylated-interferon (PEG-IFN) and ribavirin (RBV) therapy were determined around IL-28B in chromosome 19, and the strong association was also observed in spontaneous viral clearance regardless of population. These data imply that an important interaction between HCV infection and IL-28B is critical for viral persistence or clearance. PEG-IFN and RBV therapy is associated with a range of treatment-limiting adverse effects. One of the frequent side effects induced by the combination therapy is haemolytic anaemia. The severe anaemia requires the reduction of the RBV dose, which could lead to treatment failure. Genetic variants around inosine triphosphatase gene (ITPA) were associated with heamolytic anaemia. Interestingly, the significant SNPs observed in Europe and the United States were not strongly associated with Japanese population although all significant SNPs were located around ITPA gene, suggesting that SNPs typing using individual population are required for the collection of precise data. These significant SNPs would be useful for prediction prior to treatment for individualized medicine. PMID- 21972553 TI - [Virus, phage, transposon and their regulatory small non-coding RNAs]. AB - Many reports have been accumulated describing not a few microRNAs (miRNAs) in eukaryotes target viral genomes, whereas a number of viruses also encode miRNA genes. These small RNAs play important roles on viral infection and their replication. In germ cells, another small RNA, piRNA is reported to repress endogenous transposons. Furthermore, CRISPR RNA target virus/phage genomes in both archaea and bacteria. Therefore, small RNA is deeply involved in a broad range of biological defense systems. This system may be applied not only to control replication of viruses or phages but also provide implication on regulating the growth of microorganisms including pathogenic bacteria. PMID- 21972554 TI - [Bioinformatics studies on drug resistance against anti-HIV-1 drugs]. AB - More than 20 drugs have been available for anti-HIV-1 treatment in Japan. Combination therapy with these drugs dramatically decreases in morbidity and mortality of AIDS. However, due to high mutation rate of HIV-1, treatment with ineffective drugs toward patients infected with HIV-1 causes accumulation of mutations in the virus, and emergence of drug resistant viruses. Thus, to achieve appropriate application of the drugs toward the respective patients living with HIV-1, methods for predicting the level of drug-resistance using viral sequence information has been developed on the basis of bioinformatics. Furthermore, ultra deep sequencing by next-generation sequencer whose data analysis is also based on bioinformatics, or in silico structural modeling have been achieved to understand drug resistant mechanisms. In this review, I overview the bioinformatics studies about drug resistance against anti-HIV-1 drugs. PMID- 21972555 TI - [Structural mechanism of immune evasion of HIV-1 gp120 by genomic, computational, and experimental science]. AB - The third variable region (V3) of the human immunodeficiency virus type 1 (HIV-1) envelope gp120 subunit participates in determination of viral infection co receptor tropism and host humoral immune responses. Positive charge of the V3 plays a key role in determining viral co-receptor tropism. In our previous papers, we showed a key role of the V3's net positive charge in the immunological escape and co-receptor tropism evolution in vivo. On the other hand, the several papers suggested that trimeric gp120s are protected from immune system by occlusion on the oligomer, by mutational variation, by carbohydrate masking and by conformational masking. If we can reveal the mechanism of neutralization escape, we expect that we will regulate the neutralization of HIV-1. In this review, we will overview the structural mechanism of neutralization escape of HIV 1 gp120 examined by computational science. The computational sciences for virology can provide more valuable information in combination with genomic and experimental science. PMID- 21972556 TI - [Mechanism for HIV invasion via skin or mucosa]. AB - Sexual transmission of HIV is the most common mode of infection in the global HIV epidemic. In the absence of an effective vaccine, there is an urgent need for additional strategies to prevent new HIV infections. An emerging body of evidence now indicates that Langerhans cells (LC) are initial cellular targets in the sexual transmission of HIV, and CD4- and CCR5-mediated infection of LC plays a crucial role in virus dissemination. I focus on the recent advances regarding the cellular events that may occur during heterosexual transmission of HIV. PMID- 21972557 TI - [Mechanisms for inhibition of retrovirus replication by APOBEC3 family]. AB - Human cells developed the defense systems against retrovirus infections during the evolutions. These systems include retroviral restrictions by DNA cytidine deaminases of APOBEC3 family (A, B, C, DE, F, G, and H), which are potent factors to block the viral replication by blocking reverse transcription and/or integration and by hypermutating viral cDNA. In case of HIV-1, the viral protein, Vif abrogates the APOBEC3F/G function through specific machinery of ubiquitination and proteasomal degradation. Without Vif, APOBEC3F/G are incorporated into virus particles and block reverse transcription and/or integration in a newly infected cell. Recent advances in our understanding about biochemical and structure-biological characteristics of the enzymes provide new insights to reveal more detailed molecular mechanisms for anti-retroviral activity by APOBEC3 family. Here I briefly review how APOBEC3 proteins block retrovirus replications, focusing on APOBEC3G. PMID- 21972558 TI - [Viral and host factors affecting efficient revere transcription of HIV-1 genome]. AB - Reverse transcription of retroviral RNA into double stranded DNA is a characteristic feature of rertoviruses including human immunodeficiency virus type I (HIV-1). There has been accumulating evidence for the involvement of retroviral integrase (IN) in the reverse transcription of viral RNA. Here, we summarized recent our studies demonstrating direct functional roles of IN and its binding partner of host factor, Gemin2 in the reverse transcription. We established new in vitro cell-free assay to mimic natural reverse transcription and found that HIV-1 IN and host factor, Gemin2 synergistically stimulate reverse transcriptase (RT) activity. Analysis of intracellular stability and multimer formation of IN suggest that that high-ordered structures, especially tetramer formation of IN is critical for the function. In addition, Gemin2 might have a role to keep the higher-order structure of IN. Thus, we provide new aspects of reverse transcription of HIV-1 through IN and host factors in addition to RT. PMID- 21972559 TI - [Positive and negative regulation of transcription from HIV provirus]. AB - The RNA genome of retroviruses including human immunodeficiency virus type 1 (HIV 1) will be converted into DNA, called "propvirus". This proviral DNA will be integrated into host cell genome and behave like host genes. Since the step at which the viral RNA genome is converted into DNA will not allow any increase of viral genetic information because of the presence of RNaseH activity inherent to the reverse transcriptase and is responsible for the degradation of viral RNA in forming the DNA:RNA hybrid as the intermediate molecule for this conversion. However, during transcription from proviral DNA into viral RNA, hundreds and even thousands of mRNA encoding viral information will be synthesized by the action of host cellular RNA polymerase II, thus producing a large amount of progeny viral particles after translation and assembly. HIV is unique in that it contains virus specific transcriptional activator called Tat. PMID- 21972560 TI - [What's going on post-budding?]. AB - In general, the retrovirus particles become infectious on post-budding with cleavages of structural protein Gag by viral protease. Protease defective mutants bud particles normally, but the particles are non-infectious and called donuts like particle because of their morphology. The viral genomes inside the donuts like particles form very fragile dimer, which are far different from those in wild-type particles. The ordered particle maturation process is essential for infectivity of virus, but its mechanism largely remains unclear. We have constructed HIV-1 Gag cleavage site mutants to enable the steady state observation of virion maturation steps, and precisely study Gag processing, RNA dimerization, virion morphology and infectivity. As results, we found that these process progressed synchronously, but each transition point did not coincide completely. The mutual relationship between viral protein and RNA maturation is discussed for a further understanding of the retroviral life cycle. PMID- 21972561 TI - [Development of viral vectors and the application for viral entry mechanisms]. AB - Virus is identified as one of the obligate intracellular parasites, which only amplify in cells of specific living things. Viral vectors, which are developed by utilizing these properties, are available in the various fields such as basic research of medical biology or application of gene therapy. Our research group has studied development of viral vectors using properties of baculovirus or vesicular stomatitis virus (VSV). Due to the development of new baculoviral vectors for mammalian cells, it is possible to be more efficient transduction of foreign gene in mammalian cells and animals. Furthermore, pseudotype or recombinant VSV possessing the envelope proteins of hepatitis C virus, Japanese encephalitis virus or baculovirus were constructed, and characteristics of the envelope proteins or entry mechanisms of these viruses were analyzed. PMID- 21972562 TI - [Protease-dependent cell entry mechanism of coronaviruses]. AB - Previous studies have demonstrated that the SARS-CoV S protein requires proteolytic cleavage by elastase, cathepsin or TMPRSS2 for S-mediated cell-cell or virus-cell membrane fusion. Activation of viral glycoprotein (GP) by protease also has been reported for influenza virus. The most distinctive difference between influenza virus and SARS-CoV is the stage during virus replication in which viral glycoproteins are cleaved by proteases. In influenza virus, the protease makes a simple cut in the GP during maturation. In contrast, SARS-CoV S protein is cleaved by the protease following receptor-induced conformational changes. The protease cleavage site in S protein is thought to be exposed only after receptor binding. In support of this model, we reported that the S protein of mouse hepatitis virus type 2 (MHV-2), which is highly similar to the S protein of SARS-CoV, requires two-step conformational changes mediated by sequential receptor binding and proteolysis to be activated for membrane fusion. Such a mechanism allows for tight temporal control over fusion by protecting the activating cleavage site from premature proteolysis yet allowing efficient cleavage upon binding to the receptor on target cells. PMID- 21972563 TI - Polishing domestic wastewater on a subsurface flow constructed wetland: organic matter removal and microbial monitoring. AB - Microbial monitoring of constructed wetlands (CWs) treating domestic wastewater is generally scarce, despite the need of more knowledge about its biocenosis. The sanitation quality of a wastewater treated in a CW is a crucial aspect, mainly when the receiving water body is used as a swimming and/or recreation area. The present study was carried out in a horizontal subsurface flow CWplanted with Phragmites australis receiving pre-treated domestic wastewater (mean flow 50 m3 day(-1)), from a population of about 300 inhabitants. The monitoring programme undertaken during the first year operation, revealed removal efficiencies of 61% BOD5, 44% COD, and 65% TSS for inlet water with ca. 90 mg L(-1) BOD5, 157 mg L( 1) COD, and 17 mg L(-1) TSS. Total Coliform (TC) and Faecal Coliform (FC) bacteria were removed from wastewater (mean inlet values of 5 x 10(6) CFU 100 mL( 1) TC and of 9 x 10(5) CFU 100 mL(-1) FC), with efficiencies of 92 and 97%, respectively. The dynamics of microbial communities established in the system assessed by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE), had revealed a high bacterial diversity within the system, with no relevant differences in composition at the CW inlet and outlet but exhibiting temporal differences in bacterial communities. PMID- 21972564 TI - Halophytes--an emerging trend in phytoremediation. AB - Halophytic plants are of special interest because these plants are naturally present in environments characterized by an excess of toxic ions, mainly sodium and chloride. Several studies have revealed that these plants may also tolerate other stresses including heavy metals based on the findings that tolerance to salt and to heavy metals may, at least partly, rely on common physiological mechanisms. In addition, it has been shown that salt-tolerant plants may also be able to accumulate metals. Therefore, halophytes have been suggested to be naturally better adapted to cope with environmental stresses, including heavy metals compared to salt-sensitive crop plants commonly chosen for phytoextraction purposes. Thus, potentially halophytes are ideal candidates for phytoextraction orphytostabilization of heavy metal polluted soils and moreover of heavy metal polluted soils affected by salinity. Some halophytes use excretion processes in order to remove the excess of salt ions from their sensitive tissues and in some cases these glandular structures are not always specific to Na+ and Cl- and other toxic elements such as cadmium, zinc, lead, or copper are accumulated and excreted by salt glands or trichomes on the surface of the leaves--a novel phytoremediation process called "phytoexcretion". Finally, the use of halophytes has also been proposed for soil desalination through salt accumulation in the plant tissue or dissolution of soil calcite in the rhizosphere to provide Ca2+ that can be exchanged with Na+ at cation exchange sites. PMID- 21972565 TI - Effect of circulation on wastewater treatment by Lemna gibba and Lemna minor (floating aquatic macrophytes). AB - In this study, laboratory tests were performed in order to examine growth characteristics of floating aquatic macrophytes (Lemna gibba and Lemna minor) in the presence of wastewater with circulation. The results showed that circulation of the waste water enhanced the kinetics of the process, as compared to the control systems. However, prolonged application of high circulation level had a different effect. In the presence of circulation with aquatic plants, there was additional 85.3-88.2% for BODs and 59.6-66.8% for COD decreases in the water quality indicators. In this study, the effectiveness of L. gibba and L. minor with circulation addition for the removal of four heavy metals (Pb, Ni, Mn, and Cu) from waste water was also investigated. Results from analysis confirmed the accumulation of different metals within the plant and a corresponding decrease of metals in the waste water. At the end of the study of circulation, L. gibba provided the metal removal for Cu, Pb, Ni, and Mn in the waste water as the ratio of 57%, 60%, 60%, and 62%, respectively. In this context, the best results were obtained when the action of L. gibba and L. minor plants, was combined with that of circulation. It is shown that in the presence of L. gibba and L. minor plants that are supplemented with circulation, the national standards of biochemical oxygen demand (BOD5) 27-33 mgL(-1) and chemical oxygen demand (COD) 62-78 mgL(-1) for L. minor and L. gibba, respectively, were reached after treatment. The new results can be used for design calculations regarding expected removal of pollutants by aquatic floating plants. PMID- 21972566 TI - Uptake of heavy metals by native species growing in a mining area in Sardinia, Italy: discovering native flora for phytoremediation. AB - This study assessed the distribution and availability of plant uptake of Zn, Pb, and Cd present in an abandoned mine at Ingurtosu, Sardinia (Italy). Geological matrix samples (sediments, tailings, and soil from a nearby pasture site) and samples of the predominant plant species growing on sediments and tailings were collected. Mean values of total Zn, Pb and Cd were respectively (mg kg(-1)) 7400, 1800, and 56 in tailings, 31000, 2900, and 100 in sediments, and 400, 200, and 8 in the pasture soil. The metal concentration values were high even in the mobile fractions evaluated by simplified sequential extraction (Zn 7485-103, Pb 1015 101, Cd 47-4 mg kg(-1)). Predominant native species were identified and analyzed for heavy metal content in various tissues. Among the plant species investigated Inula viscosa, Euphorbia dendroides, and Poa annua showed the highest metal concentration in aboveground biomass (mean average of Zn: 1680, 1020, 1400; Pb: 420, 240, 80; Cd: 28, 7, 19 mg kg(-1), respectively). The above mentioned species and A. donax could be good candidates for a phytoextraction procedure. Cistus salvifolius and Helichrysum italicus generally showed behavior more suitable for a phytostabilizer. PMID- 21972567 TI - Adaptation of a constructed wetland to simultaneous treatment of monochlorobenzene and perchloroethene. AB - Mixed groundwater contaminations by chlorinated volatile organic compounds (VOC) cause environmental hazards if contaminated groundwater discharges into surface waters and river floodplains. Constructed wetlands (CW) or engineered natural wetlands provide a promising technology for the protection of sensitive water bodies. We adapted a constructed wetland able to treat monochlorobenzene (MCB) contaminated groundwater to a mixture of MCB and tetrachloroethene (PCE), representing low and high chlorinated model VOC. Simultaneous treatment of both compounds was efficient after an adaptation time of 2 1/2 years. Removal of MCB was temporarily impaired by PCE addition, but after adaptation a MCB concentration decrease of up to 64% (55.3 micromol L(-1)) was observed. Oxygen availability in the rhizosphere was relatively low, leading to sub-optimal MCB elimination but providing also appropriate conditions for PCE dechlorination. PCE and metabolites concentration patterns indicated a very slow system adaptation. However, under steady state conditions complete removal of PCE inflow concentrations of 10-15 micromol L(-1) was achieved with negligible concentrations of chlorinated metabolites in the outflow. Recovery of total dechlorination metabolite loads corresponding to 100%, and ethene loads corresponding to 30% of the PCE inflow load provided evidence for complete reductive dechlorination, corroborated by the detection of Dehalococcoides sp. PMID- 21972568 TI - In-situ cadmium phytoremediation using Solanum nigrum L.: the bio-accumulation characteristics trail. AB - In this study, Solanum nigrum L. was used in-situ for Cdphytoremediation in Cd polluted soil on Shenyang Zhangshi Irrigation area (SZIA) in 2008. The performance of the plant over the whole growth stage was assessed. Results showed, during the whole experimental stage, the aboveground biomass of single Solanum nigrum L. grew by a factor of 190, from 1.6 +/- 0.4 g to 300.3 +/- 30.2 g with 141.2 times extracted Cd increase from 0.025 +/- 0.001 to 3.53 +/- 0.16 mg. Both the distribution of biomass and amount of extracted Cd in the above-ground part of the plant changed according to the growth of the plant. Particularly, the percentage of biomass and extracted Cd in the stem increased from 20% to 80% and from 11% to 69%, respectively. The bioconcentration factor and transfer factor both varied significantly during the growth of the plant and the lowest values were measured at the flowering stage (0.94 +/- 0.31 and 3.48 +/- 1.14 respectively). The results in this paper provide reference values for the future research on the application of Solanum nigrum L. in phytoremediation and on chemical or/and agricultural strategies for phytoextraction efficiency enhancement. PMID- 21972569 TI - How phytohormone IAA and chelator EDTA affect lead uptake by Zn/Cd hyperaccumulator Picris divaricata. AB - In this paper, the effects of indole-3-acetic acid (IAA) and/or ethylenediaminetetraacetic acid (EDTA) on lead uptake by a Zn/Cd hyperaccumulator Picris divaricata were studied. P. divaricata responded to Pb by better root system and increased biomass in presence of phytohormone IAA, which was able to reduce the inhibiting effects of Pb on transpiration without reducing the uptake of Pb The application of 100 microM IAA increased plant transpiration rate by about 20% and Pb concentration in leaves by about 37.3% as compared to treatment exposed to Pb alone. The enhanced phytoextraction efficiency could be attributed to the mechanisms played by IAA through alleviating Pb toxicity, creating better root system and plant biomass, promoting a higher transpiration rate as well as regulating the level of nutrient elements. On the contrary, inefficiency of phytoextraction was found with EDTA or the combination of IAA and EDTA probably because most Pb was in the form of Pb-EDTA complex which blocked the uptake by P. divaricata. The present study demonstrated that IAA was able to enhance the phytoextraction of Pb by Zn/Cd hyperaccumulator P. divaricata, providing a feasible method for the phytoremediation of polymetallic contaminated soils. PMID- 21972570 TI - Deposition of particulate matter of different size fractions on leaf surfaces and in waxes of urban forest species. AB - Particulate matter (PM) is an air contaminant in urban and industrial areas that often exceeds limit values, creating serious problems due to its harmful effects on health. Planting trees and shrubs as air filters is a way to improve air quality in these areas. However,further knowledge on species effectiveness in air purification is essential This study compared four species of tree (Acer campestre L, Fraxinus excelsior L, Platanus x hispanica Mill. ex Muenchh. 'Acerifolia', Tilia cordata Mill.), three species of shrub (Forsythia x intermedia Zabel, Physocarpus opulifolius (L.) Maxim., Spiraea japonica L.), and one climber species (Hedera helix L) that are commonly cultivated along streets in Poland to capture fine, coarse and larger particles from air. Separate gravimetric analyses were performed to quantify PM deposited on surfaces and trapped in waxes. Significant differences were found between the plant species tested. The distribution of different particle size fractions differed between and within species and also between leaf surfaces and in waxes. PMID- 21972571 TI - [In Process Citation]. PMID- 21972572 TI - [Health as an interdisciplinary construction. Example of the dialogue between geography, health and territory]. AB - It is common to confuse health and medicine, but this comparison is far too limited to promote health. Health is related to the living conditions of the individual, from all points of view: food, education, housing, work, travels, health care. Obviously the latter is part of it but is just one link in a long chain. A health condition is the result of a system of multiple interactive components at a given time and in a given place: endogenous factors (physical, biological, genetic) and exogenous ones (political, economic, social and cultural environments, features of the living conditions). The discrepancies are the results of the differentiated combinations of these factors. Some contexts associate a series of health protecting factors whereas others associate factors of vulnerability. There has always been a dialogue between, on the one hand, medicine and, on the other hand, sociology, anthropology and economy. It dates back to antiquity for geography (cf: Hippocrates treatise: on air, water and places) but it disappeared at the time of Pasteur revolution. The 20th century marks the return of geography and in 2009 a French law takes hold of one of its key words "territory". Why? What are the contributions of this discipline? Maps are a strong image of this discipline, which cannot be limited to this production. Geography also contributes to the laws of distance, polarity and flows and to the notions of scale, accessibility, network, basin, space for living, territorial dynamics.... We have here a very good opportunity to establish a dialogue between health and geography. Indeed, the perception of the territorial dimension of health issues is being reinforced both through the reading of epidemics such as SARS and flues and through the discrepancies in the health conditions. This reinforcement is related to the territorialization procedures. In the field of health care planning this discipline provides us, thanks to its tools, with decision-making diagnoses necessary for the promotion of a greater territorial equity. At the time of the implementation of the HPST (Law on Hospital - Patient - Health - Territory) and ARS (Regional Agency for Health) laws and of the debates on the health territories, the emphasis will be put on the French health care system. PMID- 21972573 TI - [In Process Citation]. PMID- 21972574 TI - [What about the NICU lighting?]. AB - NICU lighting is an important element of the environment in which preterm infants continue to develop. Although several researchers have conducted studies on the subject, the existing divergence among the findings and the recommendations of neonatal experts limit the generalization of the results of these studies to guide neonatal clinical practice. While nursing practices are based on evidence and recommendations, it is essential to provide a review of the elements in the literature related to the lighting of the neonatal intensive care units. PMID- 21972575 TI - [Learning together to work together: interprofessional education, a myth or reality?]. AB - This article offers a review of the literature on interprofessional education (EIP), a form of education which brings together members of two or more professions in a joint training. In this course, participants gain knowledge through other professionals and about them. The goal of EIP is to improve collaboration between health professionals and the quality of patient care. The EIP is booming worldwide and seems for from a mere fad. This expansion can be explained by several factors: the increasing importance attributed to the quality of care and patient safety, care changes (aging population and increasing chronic diseases) and the shortage of health professionals. The expectations of the EIP are large, while the evidence supporting its effectiveness is being built. PMID- 21972576 TI - [Stress, social support and coping strategies: what influence on perceived parental self-efficacy of primiparous mothers?]. AB - Following comprehensive and semistructured interviews, (N = 30) this article questions the life changes arising in mothers six weeks after the birth of the first child. The birth of a child reflects emotional, behavioral and cognitive changes, requiring consideration and adjustments bythe mothers. We believe there are a number of factors that could impact the perceived self-efficacy and the emotional health of the mothers, and the relationship between mother and child. The research indicates areas of stress encountered by mothers and the strategies put in place by mothers to cope and overcome the stress problem. This article also questions the action taken to reduce stress by the medical team and in particularly the midwife during the birth process. The results show that all stressful events have not the same impacts on the perceived self-efficacy. Breast feeding and the crying of the babies appear to have the most impact. We believe, professional social support has a strong influence on the mothers perceived self efficacy. As well, it is important to consider the value given to people in charge of support. Thus, the research indicates the complex link between stress, social support and coping strategies and leads to a complex transactional pattern. PMID- 21972577 TI - [Social representations, associated with cardiac heart failure, of couples of whom one member is living with the illness]. AB - There is a dearth of literature on the beliefs and constructs that influence couples' experience with cardiac heart failure (HF). This article summarizes a qualitative study that aimed to describe social representations associated to HF of II couples with one member diagnosed with the illness. The social representations that emerged from the study as well as the similitude and difference between spouses trigger interesting reflections on their link with the illness experience. A difference between men and women is especially noticeable in the social representations associated to the role of the patient and of the spouse in managing the illness. Results underline the importance of offering support to both members of the couple. PMID- 21972578 TI - [In Process Citation]. PMID- 21972579 TI - [The efficacy of integrating vaccination in primary heath care program to prevent missed opportunities of vaccination in Ivory Cost]. AB - According to a nursing theory, a model to prevent missed opportunities of vaccination have been implemented in primary care service. The scope of the study was to experiment the efficacy of integrating vaccination in primary health care program in Bouake (Cote d'Ivoire). PMID- 21972580 TI - [Evaluation of the effectiveness of a protocol of intensification of mouth care (teeth brushing and chlorhexidine 0.12%) on the colonisation of tracheal aspirations in intubated and ventilated patients in intensive care]. AB - In intensive care, Ventilator-Assisted Pneumonia (VAP) is frequent with an estimated incidence of 12.6% in 2002. This infection is related to micro inhalation in the trachea of bacterial colonies present in the mouth. However, no recommendation of learned societies has been made concerning how mouth care should be carried out in order to prevent VAP. We have made the hypothesis, then, that intensified mouth care using a standard protocol that includes teeth brushing would be more effective than procedures currently being used to limit tracheal colonization. The objective of this project of research is to compare two protocols of mouth care and to evaluate endotracheal colonization after 14 days for patients who have been on mechanical ventilation for at least 24 hours. Materials and Methods. This is a randomized trial neutral for treatment. 91 patients will be assigned to each group (total of 182 patients) in order to demonstrate an increased average delay of tracheal colonization of 2 days to the power of 80%. The first group will receive a protocol consisting of three sessions per day of mouth care according to a (standard) protocol (including use of Chlorhexidine 0.12%). The second group will benefit by an intensified program consisting of six sessions per a day of mouth care (2 teeth brushings with a suction tooth brush + 4 sessions per day of mouth care with chlorhexidine 0.12%). Patients who are eligible are adults who will be on ventilation for at least 24 hours. Patients who will be excluded are: -those who have pneumonia or colonization on admission (spectum cytology examination Day 0 positive or admission is documented as for pneumonia.) -those who have been on ventilation more than 72 hours. The criteria for the principal results will be: Survival without colonization of tracheal (aspirations) (greater than 10 to the 5) (CFU/ml). Other criteria for the secondary results (jugements) will allow us to respond to the hypothesis, such as rate of tracheal colonization and VAP, length of time of ventilation and hospitalization, improvement of the state of the patient's mouth, etc. The benefits expected from this study concern the prevention of nosocomial infections by reduction of tracheal colonization with a reduction of morbidity and mortality. It will also allow a standardization of nursing care practices and formalizing of evidence-based practices. Finally, we hope to see a reduction in costs associated with VAP. A pilot study is currently ongoing and a project proposed for the (PHRIP) of 2011. PMID- 21972581 TI - [The development of "tobacco control science": progress in the fundamentals of quality health treatment]. PMID- 21972582 TI - [Not Available]. AB - CONTEXT: As part an experimental counselling project carried out with socially unstable drug-addicts to monitor the compliance with their substitution treatment. (Eymard, 2007), we could be analyse the practices of education in health. METHOD: Statistical analysis of linguistics and comprehensive analysis of the practice of professionals and the accounts of 29 subjects in a treatment centre. RESULTS: The multiplicity of obstacles to compliance and their multidirectional complicates the counselling medico-psychosocial. Two models were described in the counselling practice: an action and learning guidance model, and a model which accompanies the subject in the compliance/ non-compliance process by looking for the ties between health risks and quality of life. Sometimes are combined to fit to the process of change of the person in care. Some professionals may use alternately models, or denominate different models depending on the situation to adapt to the change process of the person in care. PMID- 21972583 TI - [Health promotion and nursing education, which challenges? Case of the nurse in a Swiss University of Applied Sciences]. AB - This work presents a research undertaken for a diploma of Master in social sciences in connexion with the conceptions of HES new graduate nurses concerning health promotion. An inductive qualitative approach has been used to explore the influence of the alternation training within the University of Applied Sciences of Health arc on their professionalisation. In addition to the semi-directing interviews, an understanding maintenance in group has been led to account for the reflexivity and difficulties of the new graduates. The results show that they spontaneously refer to the global health model, but are confused when asked to define the concept of health promotion. The practical training seems to be less professionalized in this precise field, in connection with a prevalence of the biomedical model and the nurses' increased workload. We identify socialization in the places of acute care. The results show that the formation at school accurately prepared the nurses to exert their role as a "reflexive practitioner" who takes into account the complexity of the various determinants of health with respect to the situations of care, although the lessons remain very abstract. The analysis of the results show that professionalisation of HES nurses is hesitant and fragile in the field of the promotion of health, due to several conceptual, epistemic, organisational and political factors. A "project-actions" has been worked out and has raised some levers and obstacles with its realisation. This research opens on other tracks of research, which could be able to explore more accurately the difficulties and obstacles at school and on the spot for practise and their influence on the professionalisation of the nurses-to-be. PMID- 21972584 TI - [Diagnosis and treatment of cerebral sinus thrombosis]. AB - Cerebral sinus thrombosis is a rare disease appearing mostly in young women. Typical symptoms include headache, convulsions, visual deterioration and various symptoms of neurological deficits. Magnetic resonance imaging of the brain and venous sinuses is the diagnostic cornerstone, whereby an obstructed venous sinus, thrombus mass and potential intracerebral lesions such as venous infarction or hemorrhage are diagnosed. Anticoagulant therapy should be initiated immediately once the diagnosis is confirmed. PMID- 21972585 TI - [Psychiatric evaluation of the operability of an organ transplant patient]. AB - When evaluating the eligibility of a patient for organ transplantation, psychiatric conditions possibly having a detrimental effect on the patient's prognosis should be recognized and treated in addition to somatic illnesses. Mood and anxiety disorders are often accompanied by poor general compliance. Even profound psychiatric disturbances or psychosocial problems nowadays seldom impede the enrollment of the patient to the waiting list. Psychiatric examination of the living organ donor is also always advisable before the operation. PMID- 21972586 TI - [Immunological regulation of acute inflammatory reaction]. AB - Inflammation is an acute manifestation of the activation of the immune defense. The immunological regulation of an inflammatory reaction is disturbed in many diseases, and inflammation is also involved in numerous conditions that are often considered non-inflammatory such as atherosclerosis, ischemic tissue injury, obesity and Alzheimer's disease. Especially recent progress in the research on the innate immune system has improved our understanding on the manifold cause effect relationships in the regulation of the immune reactions and opened up new possibilities to manage inflammation. PMID- 21972587 TI - [Sodium thiosulfate--new hope for the treatment of calciphylaxis]. AB - Calciphylaxis is a rare disease primarily affecting patients dependent on dialysis. It is characterised by small vessel media calcification leading to cutaneous ischemia and necrosis. The mortality rate is high with infection and sepsis being the most common causes of death. Calcium salts, vitamin D and high levels of serum calcium and phosphorus increase the risk of calciphylaxis. Current therapies including restoration of mineral homeostasis, wound care and pain control, are not entirely effective. Sodium thiosulfate, by dissolving calcium deposits, is a novel therapeutic choice for calciphylaxis. It has proved successful also in cases refractory to conventional treatment. PMID- 21972588 TI - [Boron neutron capture therapy (BNCT) as cancer treatment]. AB - Boron neutron capture therapy leads to a strong local radiotherapy effect. The efficacy of the method in cancer therapy requires sufficient accumulation of boron into and a fairly superficial location of the tumor. The efficacy and tolerability of this therapy has been investigated in Finland especially in locally recurring head and neck cancer. These tumors have responded favorably to boron neutron capture therapy and the treatment has been relatively well tolerated, although most cancers have recurred locally with few cases of durable complete remission. PMID- 21972589 TI - [Hallux valgus--several ways to treat]. AB - Hallux valgus is a progressive exertional metatarsal disturbance altering the kinematics of walking. It may be accompanied by other problems of the foot, such as hammer toe or flatfoot syndrome, symptoms of metatarsalgia or arthrosis of the small joints of the foot. Conservative treatment aims to reactivate the muscles of the foot. Operatively, placement of the 1st metatarsal to its anatomical position over the sesamoid bones is attempted to support the action of the foot muscles. When choosing the operative technique the extent and severity of the disorder as well as the objectives and risk factors of the treatment should be considered. PMID- 21972590 TI - [Psychiatric rating scales in clinical work]. AB - Psychiatric rating scales can be used to support disease screening and assessment of the severity of symptoms and effectiveness of treatment. In Finland, several rating scales suitable for both the general practitioner and the psychiatrist, are in use. The scales can be applied to mood disorders, anxiety disorders, eating disorders, substance use disorders and to the assessment of symptoms associated with psychoses. It is important not to make a psychiatric diagnosis merely on the basis of the score obtained. The use of appropriate rating scales makes the clinical work easier and quicker. PMID- 21972591 TI - [Minor trauma during pregnancy can cause severe fetomaternal hemorrhage]. AB - The principal causes of trauma in pregnancy include falls, motor vehicle accidents and violence. Blunt trauma to the abdomen increases the risk of fetomaternal hemorrhage. Massive fetomaternal hemorrhage is a rare but severe complication which can result in fetal anemia, fetal hypoxia, intrauterine death or neonatal neurologic damage. This case report defines incidence and significance of fetomaternal hemorrhage and shows via two cases that even minor maternal injury can lead to severe fetomaternal hemorrhage and risk of fetal compromise. The most common symptoms of fetomaternal hemorrhage are decreased fetal activity and movements reported by the mother. The cornerstones of evaluation of the third trimester trauma patient after abdominal hit are adequate assessment, CTG monitoring and sonographic fetal surveillance. PMID- 21972592 TI - [One case with mixed infection of Giardia lamblia, Clonorchis sinensis, and Necator americanus]. PMID- 21972593 TI - [Cloning, expression and immunologic identification of C31B8.8 gene of Caenorhabditis elegans]. AB - OBJECTIVE: To clone and express C31B8.8 gene of wild-type Caenorhabditis elegans, and study the immunological characteristic of the recombinant protein. METHODS: Total RNA was extracted from cultivated C. elegans and reversely transcribed into cDNA. C31B8.8 gene was amplified by PCR and cloned into pMD-18T vector for sequencing. The accurate sequence was subcloned into the expression vector pET 30a with (His) 6-tag. The recombinant plasmid was transformed into E. coli BL21 and followed by expression of the protein induced by IPTG. The recombinant protein was identified by using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) and Western blotting 10 BALB/c mice were randomly divided into C31B.8-immunized group and PBS + adjuvant group Mice in C31B8.8-immunized group were immunized with 40 microg of purified C31B8.8 antigen formulated in Freund's adjuvant Mice in PBS + adjuvant group received only adjuvant emulsified with PBS. All the mice received four immunizations every week with the same dose of antigen. Serum samples were collected at pre immunization and certain time after immunization and the antibody titer was analyzed by ELISA. The recombinant C31B8.8 protein and soluble components of Angiostrongylus cantonensis fourth-stage larvae were identified by Western blotting. RESULTS: The constructed recombinant plasmids were identified by enzyme digestion and DNA sequencing. MALDI-TOF-MS and Western blotting analysis showed that the recombinant C31B8.8 protein was the target protein. Compared with PBS + adjuvant group, mice immunized with purified protein C31B8.8 produced higher level of IgG. The anti-C31B8.8 serum recognized recombinant C31B8.8 protein, and reacted with soluble antigens of A. cantonensis fourth-stage larvae. CONCLUSION: C elegans C31B8 gene shows certain immunogenicity and immunoreactivity, and the soluble antigens of A. cantonensis fourth-stage larvae can react with anti C31B8.8 serum. PMID- 21972594 TI - [A case of sparganosis mansoni]. PMID- 21972596 TI - [Retrospective analysis of 39 child cases of paragonimiasis]. AB - Clinical data of 39 children with paragonimiasis treated in Chongqing Three Gorges Central Hospital during 2008-2010 were retrospectively analyzed. The cases aged from 3 to 10 years old, with 25 cases of polyserositis (64.1%), 14 cases of cerebral paragonimiasis (35.9%). Among the cases of polyserositis, all showed dyspnea,tachypnea and diminished respiration (100%). Other symptoms or signs included purulent pleurisy, orthopnea, restricted activity, distant heart sounds, purulent pericarditis, abdominal distension, and hepatomegaly. In the 14 cases of cerebral paragonimiasis, 10 cases (71.4%) complained headache, 8 cases (57.1%) with vomiting, and other symptoms such as seizures, limb rigidity associated with conscious disturbance. Eight patients were treated with surgery and praziquantel, while others with praziquantel alone. After treatment 25 cases (64.1%) were cured, 13 cases (33.3%) improved, and 1 case (2.6%) showed no change. PMID- 21972595 TI - [L-arginine enhances Th1 immune response against Plasmodium yoelii 17XL infection in DBA/2 mice via activation of dendritic cells]. AB - OBJECTIVE: To investigate the effect of L-arginine (L-Arg) during blood-stage infection by P.y17XL in DBA/2 mice. METHODS: DBA/2 mice were divided into 2 groups, 20 mice in each group. Mice were respectively administered with L-Arg (1.5 g/kg, L-Arg group) and normal saline (control group) 7 days before they were infected intraperitoneally by 1 x 10(6) pRBC. Parasitemia were detected by Giemsa stained thin-smear microscopy and survival rate were monitored daily. Flow cytometry was introduced to detect the subsets of splenic CD4+CD69+ T cells, F4/80+CD36+ macrophages, myeloid dendritic cells (mDCs) (CD11c+CD11b+), plasmacytoid dendritic cells (pDCs) (CD11c+B220+) on day 3, 5 post infection (p.i.). The levels of IFN-gamma and NO in the supernatant of splenocytes culture were detected by ELISA and Griess reaction, respectively. RESULTS: Pre-treatment of mice with L-Arg significantly decreased the parasitemia from 45% to 20% and shortened self-cure time from 22d to 20d after infection. The level of F4/80+CD36+ macrophages [(29.61 +/- 0.47)%], IFN-gamma [(485.84 +/- 39.31) pg/ml], CD4+CD69+ T cells [(7.3 +/- 0.68)%], NO [(42.51 +/- 1.32) micromol/L], mDCs(CD11c+CD11b+) [(5.51 +/- 0.87)%] and pDCs(CD11c+B220+) [(5.60 +/- 0.85)%] in L-Arg group was higher than those in control group [(36.46 +/- 1.33)%, (767.86 +/ 20.56) pg/ml, (11.27 +/- 0.97)%, (78.66 +/- 2.89) micromol/L, (10.02 +/- 0.37)%] and (9.01 +/- 0.53)%, respectively]. CONCLUSION: L-Arg enhances Th1 immune responses during the early stage of P.y17XL infection in DBA/2 mice via the activation of DCs. PMID- 21972597 TI - [Conjugation of Plasmodium falciparum Pfs25 to Pseudomonas aeruginosa ExoProtein A with different chemical linkers]. AB - OBJECTIVE: To conjugate Plasmodium falciparum Pfs25 to recombinant Pseudomonas aeruginosa Exo-Protein A (rEPA) and test the effect of conjugation using different chemical linkers. METHODS: The Pfs25 was thiolated by NAHT (DL-N acetylhomocysteine thiolactone), whereas the carrier protein rEPA was modified by Sulfo-EMCS, EMCH, SBAP and Sulfo-SIAB respectively. The Pfs25-rEPA conjugates were formed by incubating the thiolated Pfs25 with modified rEPA under certain conditions. Coomassie blue stained SDS-PAGE was performed to examine the results of the conjugation. RESULTS: The Pfs25 was successfully conjugated to the carrier protein rEPA by the linkers used in this study. For the addition of a chemical group onto the protein, the reaction between the groups of primary amine and NHS (N-hydroxysuccinimide) ester was more efficient than the reaction between the groups of carboxyl and hydrazide with EDC as a crosslinker, for the formation of a conjugate, the reaction between the groups of maleimide and free sulfhydryl was more efficient than the reaction between the groups of haloacetyl and free sulfhydryl. CONCLUSION: The Pfs25 can be conjugated to the rEPA by the chemical linkers with different conjugation efficiency and coupling proteins. PMID- 21972598 TI - [Acaricidal activities of the water extract of Xiushan Sea mud against human demodex mites]. AB - OBJECTIVE: To observe the acaricidal effect of the water extract of Xiushan sea mud on Demodex brevis and D. folliculorum. METHODS: D. brevis an d D. folliculorum were obtained with modified scraping method. Each sample contained 30 or more alive Demodex which were evenly spread on the slides with 200 microl water extract of Xiushan sea mud at a concentration of 2.5, 2.0, 1.5, 1.0 and 0.5 kg/L, respectively. With 10% sulfur emulsion as positive control and saline as blank control, each experiment group was carried out at the same time. Under room temperature of 20 degrees C and relative humidity of 70%, parasite death number was recorded at 5 min, 10 min, 20 min, 40 min, 1h, 2h, 4h, 8h, 12h and 24 h. The acaricidal rate was measured and calculated by counting method. Demodex activity and morphology were observed using microscope. RESULTS: 1.0-2.5 kg/L of the water extract of Xiushan sea mud increased the activities of both kinds of Demodex. D. brevis showed shrinkage, deformation, twisting and the bodies became shorter. The digesting vasoconstrictions of D. folliculorum also shrank and the stretching frequency of the tails moved faster. When the concentration of the sea mud extract decreased from 2.5 kg/L to 1 kg/L, the proportion of active movement of D. brevis and D.folliculorum decreased from 79.4% (27/34), 65.7% (23/35) to 68.9% (26/38), 53.8% (21/39), and the activity time extended from 15 min, 20 min to 100 min, 104 min, respectively. The 0.5 kg/L of the sea mud extract showed no significant effect on the morphology and activity of both species of Demodex. When the concentration decreased from 2.5 kg/L to 1.5 kg/L, the time to kill both Demodex spp. extended from 2 h to 8 h. The extract at a concentration of 1 kg/L showed higher acaricidal effect to D. brevis than that of positive control (P<0.05), while there was no significant difference for D. folliculorum (P>0.05) . When the concentration decreased to 0.5 kg/L, the acaricidal effect for D. brevis and D. folliculorum remarkably reduced and there was no significant difference with the control groups (P>0.05). The lowest effective concentration for both Demodex spp. was 1 kg/L. The values of 1 h median lethal concentration (LC50) of the sea mud extract for D. brevis and D. folliculorum were 1913 mg/L and 2131 mg/L, respectively. CONCLUSION: The water extract of Xiushan sea mud shows acaricidal effect to human Demodex. The effect to D. brevis is slightly better than to D. folliculorum. PMID- 21972599 TI - [Nested PCR for malaria detection and Plasmodium species identification]. AB - According to the sequences of small subunit ribosomal RNA (SSU rRNA) gene of Plasmodium spp., universal and species-specific primers were designed to detect malaria and identify species. 60 blood samples were detected by the established nested PCR method. The results were compared with those of microscopic examination. 40 blood samples were Plasmodium-positive by nested PCR with 22 samples of P. falciparum, 13 of P. vivas, 3 with P. falciparum and P. vivax mixed infection, 1 of P. ovale and 1 of unclassified malaria infection. Altogether, the coincidence between the results of nested PCR and microscopy stood for 76.7% (46/60), including 18 of P. falciparum, 11 of P. vivax and 17 negatives. Further sequence analysis and real-time PCR were performed to detect blood samples with discrepancy, results of which were the same as that of nested PCR. The amplified product of P. ovale was sequenced and showed 100% homology to the corresponding part of P. ovale SSU rRNA gene sequence (GenBank No. DQ845247), which confirmed that the case was imported ovale malaria. PMID- 21972600 TI - [Preliminary study on the immunological characteristics of permissive and non permissive hosts infected with Schistosoma japonicum]. AB - OBJECTIVE: To study the difference among immune responses of three kinds of experimental animals with different susceptibility to the infection of Schistosoma japonicum, and preliminarily explore the mechanism of the immune response in permissive and non-permissive hosts. METHODS: Twelve animals of each kind of rodents, C57BL/6 mice, Sprague Dawley (SD) rats and Microtus fortis, were randomly divided into the infected group and uninfected group each with 6 animals. In infected groups of C57BL/6 mice, SD rats, and M. fortis, each animal was infected with 20, 200 and 1000 cercariae of S. japonicum, respectively. 42 d later, all rodents were sacrificed. Adult worms in portal vein and granulomas in liver were observed and the sera were collected. The levels of cytokines IL-10 and IFN-gamma as well as serum IgG, IgG2a, and IgG1 were detected by ELISA. RESULTS: At the 42th day post infection, worms in portal vein and liver granulomas were observed in C57BL/6 mice and SD rats, but not in M. fortis. The level of IL-10 in the sera of SD rats [(2.21 +/- 0.12) pg/ml] was significantly higher than that in the sera of M. fortis [(1.64 +/- 0.39) pg/ml] and C57BL/6 mice [(0.10 +/- 0.04) pg/ml] (P<0.01). IL-10 in the sera of M. fortis was also significantly higher than that in the sera of C57BL/6 mice (P<0.01). IFN-gamma in the sera of SD rats [(0.21 +/- 0.11) pg/ml] was significantly higher than that in the sera of M. fortis [(0.11 +/- 0.03) pg/ml] and C57BL/6 mice [(0.09 +/- 0.02) pg/ml] (P<0.05), but no difference between M. fortis and C57BL/6 mice (P>0.05). The levels of IgG (1.53 +/- 0.31), IgG1 (1.48 +/- 0.44) and IgG2a (0.41 +/- 0.11) in SD rats were significantly higher than that in the sera of M. fortis (0.48 +/- 0.14, 0.15 +/- 0.03 and 0.12 +/- 0.061) (P<0.01). The levels of IgG (1.21 +/- 0.16), IgG1 (0.88 +/- 0.31) in C57BL/6 mice were significantly higher than that in the sera of M. fortis (P<0.01). IgG1 antibody is the predominant subclass in the three kinds of rodents. The levels of IL-10, IFN-gamma and antibody subclass IgG, IgG1, IgG2a in all non-infected rodents were not detected. CONCLUSION: IL-10 in non-permissive hosts, which is an essential agent in the regulation of Th2 immune response, is higher than that in permissive host It may play an important role in the resistance to schistosome in the non-permissive hosts. PMID- 21972601 TI - [The target of Musca domestica cecropin on human hepatocellular carcinoma BEL 7402 cells]. AB - Human hepatocellular carcinoma BEL-7402 cells were treated with 50 micromol/L Musca domestica cecropin for 12 h, and observed under scanning electron microscope. The effect of Musca domestica cecropin labeled with FITC (FITC cecropin) on BEL-7402 cells was detected by laser scanning confocal microscopy. The scanning electron microscopy showed that most microvilli on the surface of BEL-7402 cells disappeared at 12 h after cecropin treatment. The laser scanning confocal microscopy revealed that most FITC-cecropin combined with BEL-7402 cell membrane, and partly in the cytoplasm. PMID- 21972602 TI - [Effect of Toxoplasma gondii infection on cytokines and spermatogenic cells in rats]. AB - OBJECTIVE: To study on the fluctuation of cytokines of T helper type 1 (Th1) and T helper type 2 (Th2) after Toxoplasma gondii infection, as well as pathological damage of testis and apoptosis of spermatogenic cells in male rats. METHODS: Eighty-eight SD male rats (9-10 week old) were randomly and equally divided into normal control group and infection group. Rats in infection group were infected with 1x10(4) tachyzoites by intraperitoneal injection, while those in normal control group received same volume of PBS. On the day before infection and at the 3rd, 6th, 9th, 12th, ......, and 30th day post infection, four rats from each group were sacrificed for sera and testes. gamma-interferon (IFN-gamma) and interleukin 4 (IL-4) levels in sera were measured by ELISA. The testes were sliced and observed by microscope. The levels of apoptosis relative proteins Bcl 2 and Bax in seminiferous tubules were detected by immunohistochemistry. RESULTS: IFN-gamma in sera of infected rats increased rapidly with the peak [(518.3 +/- 83.6) pg/ml] at the 6th day post infection, and then decreased rapidly. IL-4 increased slowly with the peak [(325.0 +/- 38.6) pg/ml] at the 12th day, and then decreased. Both cytokines were significantly higher than the control, (P<0.01) in the 30-day period. Pathological examination at the 6th day post infection showed that the cell levels of testicular seminiferous tubule disturbed. The number of primary and secondary spermatocytes decreased significantly. There were few sperms within the lumen or cavity which even closed. All the changes did not recover during 30 days. Bax expression in infected rats significantly increased in spermatogenic cells especially in spermatocytes at the 3rd day (P<0.05), reached a peak (0.547 +/- 0.037) at the 6th day, and then gradually decreased to normal after 15 days. The expression of Bcl-2 in infected rats did not change significantly (P>0.05). CONCLUSION: T. gondii causes severe pathological damage in spermatogenic cells of the host. During the acute phase there appears Th1 cytokine polarization accompanied by high expression of apoptosis protein Bax, which is mainly expressed in spermatocytes. After re-balance of Th1/Th2, Bax protein expression decreases without noticeable recovery of spermatogenesis. PMID- 21972603 TI - cDNA cloning and sequence analysis of Musca domestica antifungal peptide-1 (MAF 1). AB - OBJECTIVE: To clone the cDNA sequence of Musca domestica antifungal peptide-1 (MAF-1) and analyze the amino acid sequence of MAF-1 by bioinformatics method. METHODS: Based on the primer designed according to the N-terminal amino acid sequence of MAF-1, the cDNA and amino sequence of MAF-1 were obtained by the methods of RACE and NestPCR. The accuracy of the experiment was confirmed by RT PCR The characteristic of the sequence was analyzed by bioinformatics software. RESULTS: The length of the cDNA sequence of MAF-1 was 568 bp by 3'RACE, including an open reading frame (ORF) of 441 bp length and 3'UTR of 127 bp. It was a novel sequence with the submission number of HM178948 in GenBank since none homology was found when compared with other sequences by Blast. Added with the 9 amino acids that were not used to design primer, the whole sequence of MAF-1 was 156 amino acids conferred from its cDNA. 139 bp cDNA sequence was obtained by 5'RACE and the result was consistent to 3'RACE. The result of RT-PCR showed the cDNA of MAF-1 mature peptide was accurate. The bioinformatics analysis deduced that the theoretic molecular weight and isoelectric point of the whole protein sequence of MAF-1 gene were similar to those detected. The ExPASy illustrated that the MAF-1 gene had a signal peptide. There were abundant a-helix in it, the domain located between the 128 and 153 amino acid residuals. Subcellular analysis showed MAF-1 was almost in the nucleus. Predict Protein found two protein kinase C phosphorylation sites and one N-myristoylation site, and predicted that it was not a globular protein. In the end, the three dimension image of MAF-1 was set up with 3D-pssm of ExPASy. CONCLUSION: The cDNA sequence and the amino acid sequence of MAF-1 have been obtained and analyzed successfully. PMID- 21972604 TI - [Investigation on Anopheles species and their composition in villages at different altitudes of Motuo County, Tibet Autonomous Region]. AB - OBJECTIVE: To study the anopheline species and composition in villages at different altitudes, Muotuo County. METHODS: Six villages with different altitudes were selected as the investigation spots, i.e. Gande, Zhucun, Damu, Motuo, Didong and Beibeng with an altitude 1 966 m, 1 510 m, 1 408 m, 1 178 m, 853 m and 831 m, respectively. Human-baited net traps, cow-baited traps and light traps were set up to collect adult mosquitoes. The trapped mosquitoes were counted and identified according to morphological criteria. Following the classification, the mosquitoes were killed by chloroform and dried on silica-gel, and transported to the laboratory where they were stored at -20 degrees C. Species of Anopheles maculatus complex were identified with multiple PCR method. RESULTS: 5 410 anopheline mosquitoes were collected. Two mosquitoes were captured in high altitude village, one was Anopheles gigas bailieyi, while the other was damaged and unable to identify. There were 541 (36.9%) An. pseudowillmori, 906 An. willmori (61.7%) and 21 An. peditaeniatus (1.4%) collected in semi-high altitude villages; 260 (76.3%) An. pseudowillmori, 2 An. willmori (0.6%) and 79 An. peditaeniatus (23.2%) trapped in middle altitude village; and 3265 (90.7%) An. pseudowillmori, 19 An. willmore (0.5%) and 315 An. peditaeniatus (8.8%) trapped in low altitude villages. CONCLUSION: An. pseudowillmori, An. willmore and An. peditaeniatus make the main anopheline composition. The proportion of An. willmore is higher than An. pseudowillmori in semi-high altitude villages, while An. pseudowillmori take the absolute predominance in middle and low altitude villages. PMID- 21972605 TI - [Investigation on Angiostrongylus cantonensis infection in rodents in Guangdong Province]. AB - OBJECTIVE: To investigate the natural infection of Angiostrongylus cantonensis in Guangdong Province, and to provide the scientific evidence for control measures. METHODS: The investigation was carried out in 56 villages of 28 towns of 28 counties/districts in East Guangdong, West Guangdong, the mountain area of North Guangdong and Peal River Delta of the Province from 2005 to 2010. The rodents were captured with live trap and the species identified. Angiostrongylus cantonensis adult worms were collected from the hearts and lungs of rodents, examined, counted and the sex of worms identified. RESULTS: The rodents were captured from 2005 to 2010, belonged to 2 orders, 2 families (subfamily), 4 genera and 10 species. Seven species of the rodents were found infected with Angiostrongylus cantonensis in all 28 counties/districts. Totally 5 820 rats were examined and 496 infected ones were identified, with a mean infection rate of 8.52%. The infection rate of rodents was highest in the Peal River Delta, reaching 9.8% (205/2084) (chi2=15.25, P<0.01). Rattus norvegicus had the highest infection rate of 16.9% (310/1 835) (chi2=240.91, P<0.01). The mean intensity of infection was 6.1 worms/rat. 1 125 female and 1064 male worms were found respectively (chi2=1.75, P>0.05). CONCLUSION: Natural infection of Angiostrongylus cantonensis in rodents has been found in all the 56 villages selected from the 4 regions of Guangdong Province. PMID- 21972606 TI - [Effect of control pattern with emphasis on canine deworming in a pilot of echinococcosis in highly endemic area, southern Qinghai Plateau]. AB - OBJECTIVE: To evaluate the effect of control pattern with an emphasis on canine deworming in a pilot of echinococcosis in highly endemic area of southern Qinghai Plateau. METHODS: Four pasturing villages in Xiewu Township of Chengduo County were selected as pilot villages in August of 2008. Baseline survey on awareness of echinococcosis prevention knowledge among residents and status of dogs' infection (coproantigen ELISA) was carried out in the villages. After baseline survey, measures of minimizing the control unit, setting up 15th of each month as fixed canine purgation date (praziquantel 1-2 pill/dog), giving health education to residents, selecting and training control personnel, and mobilizing local residents to participate in control of echinococcosis were performed. In October of 2009, a survey was carried out with the same contents as baseline survey to evaluate the effect of the control pattern. RESULTS: After intervention, the awareness rate on echinococcosis prevention knowledge in the residents increased from 76.1% (172/226) in 2008 to 98.8% (237/240) (chi2=55.6, P<0.01) . The positive rate of coproantigen ELISA for canine echinococcosis decreased from 32.6% (43/132) to 4.2% (5/120) (chi2=32.9, P<0.01). CONCLUSION: The knowledge awareness on echinococcosis prevention in residents increased and infection rate in dogs decreased considerably after intervention. PMID- 21972607 TI - [Efficacy of compound dihydroartemisinin/piperaquine in treatment of uncomplicated falciparum malaria in Myanmar]. AB - OBJECTIVE: To observe the therapeutic efficacy of compound dihydroartemisinin piperaquine for treatment of uncomplicated falciparum malaria in Myanmar. METHODS: From 2007 to 2008, patients aged 6 to 60 years with uncomplicated P. falciparum infection and parasite density 500 to 200 000 parasites/microl were enrolled following an informed consent. A three-day course of total 8 tablets compound dihydroartemisinin-piperaquine was administered to an adult (each tablet containing 40 mg of dihydroartemisinin and 320 mg of piperaquine phosphate), dosage for children was based on ages (details in the treatment regimen) . The indices including fever subsiding time, parasite clearance time, asexual parasite clearance time and adverse clinical responses were observed and collected on days 7, 14, 21, and 28 after treatment. RESULTS: A total of 134 patients completed the treatment. The mean fever subsiding time and mean asexual parasite clearance time were (25.5 +/- 2.8) h and (39.5 +/- 7.8) h respectively. Asexual parasite clearance rate was 100% on day 7. Four cases recrudesced on day 28 and 16 cases had slight adverse clinical responses such as uncomfortable gastrointestinal tract, headache, nausea, vomit and diarrhea, which disappeared as soon as drug withdrawal. CONCLUSION: The compound dihydroartemisinin/piperaquine shows a sound efficacy in treating uncomplicated falciparum malaria PMID- 21972608 TI - [Clinical epidemiologic features in children allergic to Dermatophagoides pteronyssinus]. AB - OBJECTIVE: To investigate the prevalence of Dermatophagoides pteronyssinus in children allergic diseases in Hangzhou and its surrounding areas. METHODS: Western blotting was used to detect the serum antibody for 9 422 children who were admitted due to clinically suspected allergic diseases. Clinical epidemiological features were analyzed for those with total IgE>100 IU/ml and Dermatophagoides pteronyssinus-specific IgE > or = 0.35 IU/ml. RESULTS: The prevalence of Dermatophagoides pteronyssinus in children with allergic diseases was 41.2% (3 878/9 422). The most common symptoms were allergic rhinitis [47.8%(1852/3 878)] and asthma [18.5%(716/3 878)]. The allergic diseases were most prevalent in July, August and October. The diseases were more prevalent in children over 3 years old and above. more in males [68.8% (2668/3878)] than females [31.2% (1210/3878)]. CONCLUSION: Data suggest that Dermatophagoides pteronyssinus is an important allergen causing allergic diseases in children in Hangzhou. PMID- 21972609 TI - [Nine cases of hookworm infection in the small intestine detected by capsule endoscopy]. PMID- 21972610 TI - [Illustrated keys to families and genera of the superfamily Ixodoidea under new taxonomic system]. AB - Since molecular biology techniques were applied in the phylogeny of ticks in the late 20th century, changes have taken place in the nomenclature and taxonomy of ticks. However, the illustrated keys to families and genera of ticks published in China were incompetence and the taxonomic system was out of date. This article presents a manual of illustrated keys to families and genera of the superfamily Ixodoidea based on the taxonomic system proposed by Barker and Murrell (2004), and provides a foundation for morphological identification of ticks. PMID- 21972611 TI - [Application of immune colloidal gold technique on the diagnosis of parasitoses]. AB - Immune colloidal gold (ICG) technique is a simple, rapid, accurate diagnosis method. At present, ICG technique has been widely applied in the accessory diagnosis of parasitoses, and this article reviews the latest progress of ICG technique applied in parasitology. PMID- 21972612 TI - [Research progress on the relationship between osteopontin and hepatic echinococcosis]. AB - Osteopontin is a negatively charged, hydrophilic secreted phosphorylated glycoprotein. It is synthesized and secreted by a variety of cells, and is found in various tissues and cells. The protein is similar in structure to matrix proteins, has the characteristics of cytokines in function and involved in a series of pathological processes. Recent studies confirmed that osteopontin is highly expressed in liver hydatid cyst and may play an important role in cyst formation. PMID- 21972613 TI - [Application of in vitro cultivation technique for metacestodes in study of Echinococcus spp]. AB - With the development of the in vitro cultivation of Echinococcus metacestodes, the technique is widely applied in research areas such as the pathogenic biological characteristics and the mechanism of infection and pathopoiesis of echinococcus, and development of novel therapeutic agents against echinococcosis. These will help futher understand the disease and its control. This paper reviews the application of the in vitro cultivation technique of Echinococcus spp. PMID- 21972614 TI - [Effect of epitope-based peptide-DNA dual vaccines against Schistosoma japonicum in mice]. AB - A C-T-B PDDV mixture of the three constructed epitope-based peptide-DNA dual vaccines (PDDV) containing the CTL (C), Th (T) and B-cell (B) epitopes from Sj22.6 tegument (C-PDDV, T-PDDV and B-PDDV) with a 1:1:1 ratio was prepared. Thirty-six mice were randomly divided into six groups averagely named as 18K group, PBS group, C-PDDV group, T-PDDV group, B-PDDV group, and C-T-B PDDV group. All the mice received three immunizations at 2-week intervals with the same dose of antigen (10 microg DNA+28 microg peptide). One week after the last immunization, the mice were sacrificed, the spleens were removed and splenocytes were collected. Splenocyte proliferation was assayed by[3H] TdR incorporation after stimulation with soluble worm antigen (SWA). Levels of IFN-gamma and IL-4 in the splenocyte culture supernatants were determined by ELISA. The results showed that IFN-gamma content in T-PDDV group [(76.0 +/- 11.2) pg/ml] was higher than that of PBS [(13.0 +/- 2.1) pg/ml] and 18K control groups [(14.0 +/- 3.2) pg/ml] (P<0.01). IL-4 level in T-PDDV [(152.0 +/- 21.1) pg/ml] and C-T-B mixture groups [(86.0 +/- 12.2) pg/ml] was higher than others (P<0.01 and P<0.05). The splenocytes from T-PDDV group showed a significant increase in proliferation compared with PBS and 18K control groups after stimulation by SWA (P<0.01). However, there was no significant difference in splenocyte proliferation among C T-B, PBS and 18K control groups (P>0.05). These findings indicate that T-PDDV and C-T-B PDDV mixture induces stronger immune response than that of C-PDDV or B PDDV. PMID- 21972615 TI - [Impacts on the duration of vaginal bleeding and the levels of serum estradiol (E2) and progesterone (P) for patients of midtrimester induction of labor treated with moxibustion at Guanyuan (CV 4) and Shenque (CV 8)]. AB - OBJECTIVE: To verify the efficacy of moxibustion at Guanyuan (CV 4) and Shenque (CV 8) on the duration of vaginal bleeding for patients with midtrimester induction of labor and explore its mechanism. METHODS: One hundred cases of midtrimester induction of labor were divided randomly into an observation group (50 cases) and a control group (50 cases). In control group, on the day of labor induction, Mifepristone was taken orally and intraamnionic injection of Rivanol was administered in the morning. In the morning on the second day, Misoprostol was taken orally. After delivery, the uterine curettage was given and 10 U Oxytocin was injected intramuscularly. In observation group, on the basis of the treatment as control group, moxibustion was given in combination. After Rivanol injection, moxibustion was applied to Shenque (CV 8) and Guanyuan (CV 4), for 15 min each time, once every 8 h. Totally, 4 treatments were required. The mean duration of vaginal bleeding was observed and the levels of serum estradiol (E2) and progesterone (P) were determined before and after treatment in two groups. RESULTS: The mean duration of vaginal bleeding was (8.82 +/- 2.98) days in observation group, which was shortened apparently as compared with (10.59 +/- 3.46) days in control group (P < 0.05). After treatment, the level of serum E2 increased and that of P decreased in either group (all P < 0.01). The increase of E2 in observation group was superior to that in control group (P < 0.05). CONCLUSION: Moxibustion at Guanyuan (CV 4) and Shenque (CV 8) may shorten the duration of vaginal bleeding for patients with midtrimester induction of labor. Probably through the increase of serum E2 level and the decrease of P level, the uterine contraction is effectively enhanced and the excretion of placental villi and deciduas is promoted. As a result, endometrial repair occurs rapidly. PMID- 21972616 TI - [Impacts of electroacupuncture on left hippocampus NAA/Cr for patients of Uygur and Han nationality with mild cognitive impairment]. AB - OBJECTIVE: To observe the clinical efficacy of electroacupuncture (EA) on mild cognitive impairment (MCI) for patients of Uygur and Han nationality and explore the national diversity among the patients with MCI. METHODS: Twenty-five cases were divided into Han nationality group (15 cases) and Uygur nationality group (10 cases) according to patient's nationality. In either group, EA was applied to Baihui (GV 20), Fengchi (GB 20), Xuanzhong (GB 39), Fuliu (KI 7), Sanyinjiao (SP 6) and Taixi (KI 3), once per day, 15 treatments made one session and there were 5 days at the interval among the sessions. Totally, 3 sessions of treatment were required. The proton magnetic resonance spectroscopy (1H-MRS) was used to observe the changes in the ratio of N-acetylaspartate and creatine (NAA/Cr) on the left hippocampus for the patients in two groups before and after treatment as well as the changes in the results of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) separately. RESULTS: NAA/Cr in Uygur nationality group was higher than that in Han nationality group before treatment (1.659 +/- 0.418 vs 1.137 +/- 0.190, P < 0.05). After treatment, MMSE and MoCA scores all increased apparently as compared with those before treatment in two groups (P < 0.05, P < 0.01), and NAA/Cr on the left hippocampus in either group was up-regulated as compared with that before treatment (both P < 0.01). CONCLUSION: EA can improve the overall cognitive function for the patients with MCI. There is the national diversity in the partial brain metabolite level between Uygur patients and Han patients with MCI. PMID- 21972617 TI - [Discussion on the relationship between acupuncture manipulation and effect]. PMID- 21972618 TI - [Twenty-four cases of Tourette's syndrome treated by acupuncture combined with needle pricking Sifeng (EX-UE 10)]. PMID- 21972619 TI - [Clinical observation on depression treated by electroacupuncture combined with western medicine]. AB - OBJECTIVE: To evaluate the clinical therapeutic effect of depression treated by acupuncture and electroacupuncture combined with western medicine. METHODS: Seventy-five patients were randomly divided into 3 groups. In control group, 30 cases were treated by SSRI with oral administration; in observation group 1, 25 cases were treated by acupuncture therapy combined with SSRI, and Shenting (GV 24), Baihui (GV 20), Dazhui (GV 14), Shendao (GV 11) and Zhiyang (GV 9) etc. were selected with regulating qi needling method; in observation group 2, same acupoints were selected with routine needling method, and 20 cases were treated by electroacupuncture therapy combined with SSRI, Baihui (GV 20) and Yintang (EX HN 3) etc. were treated by electroacupuncture. The clinical therapeutic effects and Hamilton Depression Scale scores were evaluated after 1, 2, 4 and 6 weeks treatment. RESULTS: The total effective rates of observation group 1 and 2 were 100.0%, superior to that of 73.3% in control group (both P < 0.05). The total scores of HAMD on each time point dropped, and there were significant differences compard with those before treatment in 3 groups (P < 0.01, P < 0.05); the total scores of HAMD after 1, 2 and 4 weeks improved more obviously than that in control group (P < 0.01, P < 0.05), and there was no significant difference among groups after 6 weeks (all P > 0.05). After one week treatment, the comparison of total scores of HAMD in observation group land 2 indicated significant differences (P < 0.05); after 2, 4 and 6 weeks treatment, there were no significant differences between groups (all P > 0.05). CONCLUSION: The acupuncture therapy and electroacupuncture combined with western medicine for treating depression have better effects than medicine treatment; and there is no obvious difference between acupuncture therapy and electroacupuncture therapy, however, the effect works fast by electroacupuncture. PMID- 21972620 TI - [Blood-letting puncture at Pishu (BL 20) as main for stye]. PMID- 21972621 TI - [Impacts on carotid arterial vessel and blood flow in treatment of carotid atherosclerosis with acupuncture and moxibustion]. AB - OBJECTIVE: To assess the impacts of acupuncture and moxibustion on carotid arterial vascular structure and blood flow parameters for the patients with carotid arteriosclerosis. METHODS: Sixty-eight cases were randomized into an acupuncture-moxibustion group (35 cases) and a medication group (33 cases). In the acupuncture-moxibustion group, Renying (ST 9), Neiguan (PC 6), Zusanli (ST 36), etc. were selected, moxibustion was applied at Zusanli (ST 36). In the medication group, Enteric-coated aspirin was taken orally. The high-frequency ultrasonography was applied to detect common carotid artery (CCA), intima-media thickness (IMT), peak systolic velocity (PSV), end diastolic velocity (EDV), pulsatility index (PI) and resistance index (RI) before and after treatment for the comparative analysis. RESULTS: After treatment, in comparison between acupuncture-moxibustion group and medication group, CCA got bigger [(8.16 +/- 0.80) mm vs (7.69 +/- 0.61) mm, P < 0.01], IMT became thinner [(1.05 +/- 0.09) mm vs (1.10 +/- 0.09) mm, P < 0.05], PSV and EDV were accelerated (all P < 0.01), and PI and RI were down-regulated (P < 0.05, P < 0.01). CONCLUSION: Acupuncture and moxibustion provides a good efficacy on the improvement in carotid arteriosclerosis and blood flow in carotid artery, which contributes to the alleviation of ischemic cerebrovascular diseases and prevention from the occurrence and development of them. PMID- 21972622 TI - [Moxibustion yintang (EX-HN 3) acupoint for insomnia of sleep difficulty]. PMID- 21972623 TI - [Comparative observation of the efficacy on acute gouty arthritis between acupuncture combined with infrared irradiation and western medicine]. AB - OBJECTIVE: To compare the efficacy difference in treatment of acute gouty arthritis between acupuncture combined with infrared irradiation and Indomethachin as well as observe the impacts on liver function. METHODS: One hundred and sixty cases of gout were randomized into an acupuncture group (80 cases) and an Indomethachin group (80 cases). In acupuncture group, acupuncture was applied to Zusanli (ST 36), Sanyinjiao (SP 6), Quchi (LI 11), Xuehai (SP 10), Yanglingquan (GB 34) and Ashi points. Additionally, infrared irradiation was used in the local area. The treatment was given once daily. In Indomethachin group, Indomethachin was taken orally, 25 mg each time, three times per day. The treatment lasted for 5 days in either group. Separately, before and after treatment, pain severity and the levels of blood uric acid (BUA), erythrocyte sedimentation rate (ESR), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected. Additionally, the efficacy and the impacts on liver function were assessed. RESULTS: The curative rate was 52.5% (42/80) in acupuncture group, which was superior to 22.5% (18/80) in Indomethachin group (P < 0.01). In acupuncture group, the analgesia efficacy was better than that in Indomethachin group (P < 0.01) and the effect on reducing BUA and ERS levels was same as that in Indomethachin group (all P > 0.05). After treatment, ALT and AST levels had no changes in acupuncture group, but they increased apparently in Indomethachin group (all P < 0.01). CONCLUSION: Acupuncture combined with infrared irradiation achieves superior efficacy on acute gouty arthritis as compared with oral medication of Indomethachin and the therapy provides a significant effect on analgesia and does not bring the damage of liver function. PMID- 21972624 TI - [Magical effect achieved after fainting needle]. PMID- 21972625 TI - [Clinical observation of lumbar spinal stenosis treated with deep puncture at Jiaji (EX-B 2)]. AB - OBJECTIVE: To explore the clinical efficacy on lumbar spinal stenosis treated with deep puncture at Jiaji (EX-B 2) with round-sharp needle. METHODS: One hundred and fifty cases of lumbar spinal stenosis were divided randomly into a deep puncture at Jiaji (EX-B 2) group (deep puncture group) and a conventional needling group, 75 cases in each one. In deep puncture group, the round-sharp needle was used to puncture Jiaji (EX-B 2) deeply to the nerve root in vertebral canal. Additionally, the conventional acupuncture with filiform needle was applied at the acupoints selected according to the symptoms, such as Shenshu (BL 23), Weizhong (BL 40), Zusanli (ST 36) and Zhibian (BL 54), etc. In conventional needling group, acupuncture with filiform needle was adopted at the acupoints as those in deep puncture group. The clinical symptom scores and efficacies of the patients in two groups were observed after 4 weeks treatment and 3 months of follow-up visit separately. RESULTS: After treatment and in follow-up visit, the clinical symptom scores all increased apparently for the patients in two groups (all P < 0.01). The result in deep puncture group was superior to that in conventional needling group (both P < 0.01). In deep puncture group, the total effective rates were 100.0% (75/75) and 96.0 (72/75) after treatment and in follow-up visit respectively, which were all superior to 92.0% (69/75) and 84.0% (63/75) in conventional needling group (both P < 0.05). CONCLUSION: The deep puncture at Jiaji (EX-B 2) with round-sharp needle achieves superior efficacy as compared with the conventional needling therapy in treatment of lumbar spinal stenosis. The prognosis of it is better and the disease is hardly recurred. PMID- 21972626 TI - [Effect of electroacupuncture and acupoint injection on expression of plasma proinflammatory cytokines and motilin for patients with early postoperative inflammatory intestinal obstruction]. AB - OBJECTIVE: To verify the efficacy of electroacupuncture (EA) and acupoint injection on early postoperative intestinal obstruction and explore its mechanism. METHODS: One hundred and sixteen cases were divided randomly into two groups. In control group (56 cases), the conventional western medicine was applied, including gastrointestinal decompression, parenteral nutrition (PN), anti-inflammation and supporting therapy. In observation group (60 cases), on the basis of the treatment as control group, EA and acupoint injection with Neostigmine were supplemented. Zusanli (ST 36), Shangjuxu (ST 37)/Xiajuxu (ST 39) and Dachangshu (BL 25) were selected as main points. Before treatment and after 3 days treatment, the levels of plasma interleukint (IL-6), tumor necrosis factor alpha (TNF-alpha) and motilin (MOT) were determined. RESULTS: In observation group, the mean recovery time of bowel sound and the mean frequency of passing gas were less than those in control group (both P < 0.01). After treatment, in either group, the levels of IL-6 and TNF-alpha were down-regulated as compared with those before treatment (all P < 0.01). After treatment, in observation group, IL-6 level was (15.2 +/- 4.1) pg/mL and TNF-alpha level was (18.3 +/- 6.5) pg/mL. They were (35.5 +/- 7.2) pg/mL and (52.7 +/- 12.3) pg/mL respectively in control group, indicating significant difference in statistics between two groups (both P < 0.01). In either group, MOT level increased after treatment as compared with that before treatment (both P < 0 01). After treatment, in observation group, the increase of MOT level was superior to that in control group [(190.7 +/ 48. 5 ) pg/mL vs (114.6 +/- 36.9) pg/mL, P < 0.01]. CONCLUSION: Electroacupuncture and acupoint injection are significantly effective in the treatment of early postoperative intestinal obstruction. This therapy may inhibit the release of inflammatory factors to reduce intestinal wall edema and it may promote MOT secretion to increase intestinal peristalsis. As a result, the recovery of gastrointestinal function is promoted. PMID- 21972627 TI - [Primary investigation on fumigation and moxibustion in treatment ulcer and sore of yin syndrome]. AB - To explore the fumigation and moxibustion therapy in treatment of ulcer and sore of yin syndrome. The fumigation and moxibustion therapy is the combination of fumigation and moxibustion, in which, smoking fumigation is provided with warming effect and the actions as moxibustion. This therapy works on the efficacy of both fumigation and moxibustion. In treatment, different herbal medicines can be selected flexibly, acting on dispersing yin and rescuing yang. The fumigation and moxibustion therapy can drain toxin and remove ulcer and sore. It contributes to the treatment of boils and chronic sores of yin syndrome and promotes wound healing. PMID- 21972628 TI - [Twenty-one cases of chronic alcoholic nervous disease treated with acupuncture]. PMID- 21972629 TI - [Peripheral facial paralysis treated with the adapted acupuncture technique of heat-producing needling]. AB - OBJECTIVE: To improve the manipulations of traditional heat-producing needling, and observe its therapeutic effect on peripheral facial paralysis. METHODS: Acupuncture was adopted for all the 50 patients with peripheral facial paralysis. Acupoints such as Dicang (ST 4), Jiache (ST 6), Qianzheng (Extra), Fengchi(GB 20), Yifeng (TE 17) of the affected side, Hegu (LI 4) of the healthy side, Shousanli (LI 10), Zusanli (ST 36) and Taichong (LR 3) of both sides were adopted. And an adapted heat-producing needling was applied. With the left thumb of the doctor press at the point, the needle was rotated slowly with the right thumb moving forward and index finger moving backward to maintain the needling sensation. Then, heavier pressure was given with the left thumb, and a 9-time lifting and thrusting manipulation with small amplitude, low and even frequency by the right thumb and the index finger. Heavy pressure was maintained by the left thumb, and the needle was inserted by the right thumb and index finger to promote the needling sensation. Thus, the tip of the needle was always kept at the level where the needling sensation appeared. Therefore, a heat sensation can be felt by the patient under the needle or at the distal area. The treatment should be given once a day. And therapeutic effect was observed after 15 times continue treatment. RESULTS: All the 50 patients were cured without any sequela. CONCLUSION: Adapted heat-producing needling can promote the recovery of the function of facial muscle, and the effect of treatment of peripheral facial paralysis with the manipulation is confirmed. PMID- 21972630 TI - [Clinical experience of recessive pain point]. PMID- 21972631 TI - [Xie's articular needling and four pain-relieving points]. AB - Xie's articular needling is handed down from the older generations of the family of Mr. XIE Jiguang, which is approved to have extensive indications and capable to treat various pain syndromes and Bi syndromes. Articular needling is a technique of puncturing the area at the junction of the joints, tendons and muscles. Local points and distal points are often combined in the application. The four pain-relieving points are held as distal points in articular needling, which refers to Sanjian (LI 3), Houxi (SI 3), Taibai (SP 3) and Shugu (BL 65). If pain occurs at one side of the body, the four points are supposed to be selected on the opposite side the affected area. While if pain occurs on both sides or for chronic cases, all the 8 points on both sides should be applied. For treatment of local and chronic pain, local points must be combined. Reinforcing manipulations with superficial insertion should be applied for deficient syndrome at the healthy side in most of the situations. Moreover, points around the umbilicus should be selected for tonifying the primary qi. PMID- 21972632 TI - [Abdominal acupuncture as main for vertigo]. PMID- 21972633 TI - [GUO Jian-Hua's experiences of acupoint selection of muscular injury treated with acupuncture]. AB - To introduce the clinical experience and theories of spondylopathy treated with Points Jiaji (EX-B 2), intractable pain and numbness of limbs treated with acupoints of yin meridians, disorders of lumbar vertebra with combination of acupoints in abdomen and lumbar region and muscular injury of joints by acupuncture Kinesitherapy. PMID- 21972634 TI - [Combination of acupoints based on the theory of qi tonification, blood regulation and strengthening the primary source]. AB - The acupuncture technique of tonifying qi, regulating blood and strengthening the primary source of human life is established on the base of the new pathology of dementia due to dysfunction of sanjiao by Prof. HAN Jing-xian. It is held that Tanzhong (CV 17), Zhongwan (CV 12), Qihai (CV 6), Xuehai (SP 10), Zusanli(ST 36) and Waiguan (TE 5) were the basic points for treatment of dementia. There are 3 characteristics of the point combination. Firstly, emphasis should be put on regulation of the stomach and the spleen so as to promote transportation, transformation and distribution; secondly, monarch, minister, assistant and guide points should be selected on the base of meridians, and more attention should be paid to the entity and connections among organs; and thirdly, treatment should be given according to physiological functions of the viscera. PMID- 21972635 TI - [Correctly distinguishing the relationship between abnormal conditions and adverse reactions of acupuncture]. PMID- 21972636 TI - [Effects of electroacupuncture on IL-2-IFN-NKC immunity immunoloregulation net and IL-2 receptor in rats with exercise stress]. AB - OBJECTIVE: To explore the effects of electroacupuncture on exercise-induced immunosuppression in rats and its mechanism. METHODS: Sports immunosuppressive model was established successfully by the rats were conducted high intensity swimming training 150 min/day, 6 days/wk for 8 weeks in this study. Forty-three SD rats were randomly divided into a control group (group A, n = 10), a high intensity swimming training group (group B, n = 17), and a high intensity plus electroacupuncture group (group C, n = 16). Group A did not receive any intervention. Group B was conducted 150 min/day, 6 days/wk swimming training for 8 weeks. Group C was treated with electroacupuncture at "Baihui" (GV 20), "Guanyuan" (CV 4) and "Zusanli" (ST 36) after every exercise-time from the second week, once each day for 7 weeks. The changes of the rats' weight, gamma interferon (gamma-IFN), interleukin-2 (IL-2), solubility IL-2 receptor (SIL-2R) and nature killer cell (NKC) were detected. RESULTS: (1) Compared with group A, gamma-IFN and IL-2 in group B were significantly decreased (P < 0.01, P < 0.05), and NKC in group C was significantly increased (P < 0.01). Meanwhile, gamma-IFN and NKC in group C were both significantly higher than that in group B (P < 0.05, P < 0.01). (2) Compared with group A, the weight of the rats in group B and group C were significantly decreased (both P < 0.01), but SIL-2R in group B was significantly increased (P < 0.05). The weight of the rats in group C was significantly higher than that in group B (P < 0.05) and SIL-2R in group C was significantly lower than that in group B (P < 0.01). CONCLUSION: Lasting gravis exercise stress does decrease the immune function in rats and is even inhibited significantly, but electroacupuncture can up-regulate the exercise-induced immunosuppression. PMID- 21972637 TI - [Experimental study on effects of acupoint application with Leima type II plaster on collagen-induced arthritis in rats]. AB - OBJECTIVE: To observe the therapeutic effect of acupoint application with Leima type II plaster on collagen-induced arthritis (CIA) in rats and probe its mechanism. METHODS: Bovine type II collagen was injected intradermally into the middle line of the back to induce CIA model with 48 Wistar rats. Then the rats were randomly divided into a model control group (group A), a matrix control group (group B), acupoint application group with plaster of low concentration (group C) and high concentration plaster group (group D), 12 rats in each group. Group C and group D were treated with low and high concentration of Leima type II plaster, and "Shenzhu" (GV 12), "Zhiyang" (GV 9) and "Mingmen" (GV 4) were selected, each application for about 15 hours, once each day for 30 days. Group B was used the same method of acupoint application except using non-drug matrix plaster, and group A was not given any treatment. The morphous and the histopathological changes of affection joint were observed. RESULTS: The paw edema volume after 30 days treatment in group C was significantly lower than that in group B (P < 0.01), and the anti-type II collagen antibody level after 15 days treatment in group C was significantly lower than that in group A (P < 0.05), and the synoviocytes proliferation of the knee joint in group C was significantly lower than that in group A and group B (both P < 0.01). The paw edema volume after 25 days treatment, arthritic index after 20 days treatment, pathological change of the paw and the synoviocytes proliferation of the knee joint in group D were significantly lower than those in group A and group B (P < 0.01, P < 0.05), and the anti-type II collagen antibody level after 15 days treatment in group D was significantly lower than that in group A (P < 0.05), and the paw edema volume and the arthritic index after 25 days treatment in group D were significantly lower than those in group C (P < 0.05, P < 0.01). CONCLUSION: Acupoint application with Leima type II plaster has a good therapeutic effect on CIA rats and the protective mechanism is related to the reduction of anti-type II collagen antibody level so as to carry out anti-inflammatory effect and immunosuppression. PMID- 21972638 TI - [Discussion on the Chinese edition of the WHO Standard Acupuncture Point Locations in the Western Pacific Region]. AB - Discussion is made on three aspects of the Chinese section with regards to desperate translations, mistranslations and inconsistent translation format of the WHO Standard Acupuncture Point Locations in the Western Pacific Region (Chinese-English bilingual edition), in the hope to provide some constructive references to help perfecting this book. PMID- 21972639 TI - [Discussion on the constructing principle of syndrome differentiation system according to meridian and collateral theories]. AB - According to the meridian and collateral theories in the Internal Classic, the authors proposed that the construction of the syndrome differentiation system with science characteristics of acupuncture and moxibustion should follow the principle of systemic structure and physiological function. The establishment of the whole frame structure of syndrome differentiation system according to meridian and collateral theories should base on the principle of systemic structure and the establishment of symptom of each syndrome should base on the principle of physiological function. PMID- 21972640 TI - [Innovation in clinical teaching of acupuncture]. AB - To meet the needs of clinical teaching, it is reviewed and studied on the course content, teaching method and conception of teaching in clinical teaching of acupuncture. It is suggested that the modern medical knowledge should be well integrated in clinical practice; it is worthy to introduce the researches at home and abroad, academic development and new techniques; the course content should be improved in the integration of course content and the curriculum arrangement. The perfect teaching methods should be adopted such as experiencing teaching, problem based teaching, open teaching and improving evaluation system, etc. It is sound to cultivate and encourage the mode of Chinese medicine thinking and the standardized concept in order to promote the innovation in clinical teaching of acupuncture. PMID- 21972641 TI - [Deviation index of eye and mouth on peripheral facial paralysis]. AB - Differences of some points, levels and angles of the healthy and affected sides of patients with peripheral facial paralysis were picked out according to photographs. Through analysis of the index between the healthy and affected side of the patients and the difference between healthy people and patients, it is approved that those special points, levels and angles, which are called as deviation index of eye and mouth, can evaluate peripheral facial paralysis objectively and judge the degree of deviation. Therefore, it provides references for the diagnosis of facial paralysis and its degree judgement. PMID- 21972642 TI - [Comparative observation on curative effects of stenosing tenovaginitis of flexor digitorum treated with acupuncture knife therapy and blocking therapy]. AB - OBJECTIVE: To compare the curative effects on stenosing tenovaginitis of flexor digitorum treated with acupuncture knife therapy and blocking therapy so as to explore the better method. METHODS: Three hundred and four cases were randomly divided into acupuncture knife therapy group (164 cases) and blocking therapy group (140 cases). In acupuncture knife therapy group, hooking and cutting were applied on the pressure points and scleromas with Ren's hooked acupuncture knife; routine blocking therapy was applied in blocking therapy group. The curative effects of both groups after 1-2 treatments and the recurrence after treatment in following 6 months were observed. RESULTS: The curative rate was 98.2% (161/164)in acupuncture knife therapy group, superior to that of 65.7% (92/140) in blocking therapy group; the recurrence rate was 1.9% (3/161) in acupuncture knife therapy group, inferior to that of 37.0% (34/92) in blocking therapy group. The differences are significant between groups (both P < 0.01). CONCLUSION: The curative effect of stenosing tenovaginitis of flexor digitorum treated with acupuncture knife therapy is superior to that of blocking therapy, with low recurrence rate. PMID- 21972643 TI - [Case of moyamoya disease]. PMID- 21972644 TI - [Master of Chinese medicine: the career life of Professor HE Pu-Ren]. AB - With his unique comprehension, theoretical contribution and technique of acupuncture, Professor HE Pu-ren has devoted himself into the career of Chinese Medicine for 70 years. Besides the professional contributions, his academic spirit and idea of humanities are also handed down to the next generation. And it is held that his success rests with the spirit of both imitation of the ancients and innovation as well as the practical idea and insistence. PMID- 21972645 TI - [Discussion of relation between acupuncture methods and the directions of qi in meridians]. AB - To search ancient literature and Chinese medicine references, consult the modern humanities research achievement, and discuss the meridians theories such as "going and coming", "going along and against", "acupuncture method of reinforcing and reducing", and "deficiency and excess" etc. the results show that the ancient's space and time idea, meridian qi moving are manifested in meridian theory, and play an important role in "the unity of heaven and humanity". The pulse and circulation of meridian qi can be checked by the method of "waiting for qi arriving", and the acupuncture method of reinforcing and reducing is applied due to the "waiting for qi arriving", in order to promote qi in line with time. Nowadays, compared with ancient method, the acupuncture method of reinforcing and reducing in teaching material is lack of the time factor. PMID- 21972646 TI - [Mild moxibustion at Xuehai (SP 10) for senile pruritus]. PMID- 21972647 TI - [Acupuncture at back-shu points with long-round needle for 194 cases of acne]. PMID- 21972648 TI - [Acupuncture at different meridians based on syndrome differentiation for 30 cases of cervical spondylosis]. PMID- 21972649 TI - [Eighty cases of lumbar spinal stenosis treated by electroacupuncture combined with injection through vertebral canal]. PMID- 21972650 TI - [Forty cases of supraspinal syndemitis of thoracic segments treated by acupuncture combined with ultrashort wave therapy]. PMID- 21972651 TI - [Examine and correct positioning on the Shangguan (GB 3) point]. PMID- 21972652 TI - [Blood-letting with three-edge needle and acupuncture for acute catarrhal conjunctivitis in the summer]. PMID- 21972653 TI - [Forty-four cases of humeral epicondilitis treated by analog needling method]. PMID- 21972654 TI - [Acupuncture at five hu points for narrow radial styloid tenosynovitis]. PMID- 21972655 TI - [Electric-heat needling for 27 cases of stenosing tenosynovitis of radial styloid]. PMID- 21972656 TI - [Advances in cooperativity and mechanism of combination of Back-shu and Front-mu points]. AB - The articles related with combination of Back-shu and Front-mu points searched in CNKI and Pubmed databases during the past 10 years were studied. The conclusions indicate that the application of combination of Back-shu and Front-mu points has solid theoretical basis and experimental evidence, and it is proved that the combination of Back-shu points and Front-mu points is effective in clinic practice. However, the mechanism study still rest on the level of spinal cord, and the breakthrough of combination of Back-Shu and Front-Mu points study is that whether the superior nerve centre involves on the regulation of zang-fu organs by combination of Back-shu and Front-mu points. The key point in future study is to explore the central control mechanism of combination of Back-shu and Front-mu points. PMID- 21972657 TI - Immune reconstitution inflammatory syndrome in leprosy. AB - Immune reconstitution inflammatory syndrome (IRIS) is a paradoxical deterioration in the clinical status of a patient infected with human immunodeficiency virus (HIV) on highly active antiretroviral treatment (HAART). The immune suppression caused by the virus can initially suppress the clinical manifestations of leprosy which can then be unmasked after treatment with HAART or an inflammatory reaction can occur in the initial months of therapy, resulting from dysregulated recovery of immunity to specific antigens. Both these conditions are identified as IRIS in leprosy. Though this syndrome is a widely recognized entity presently, there is still a lack of universally acceptable diagnostic criteria for the condition. The first case published case of leprosy- associated immune reconstitution disease was reported in 2003 and about 47 confirmed cases of IRIS in leprosy have been reported since then, mostly from Brazil and India. Anti-inflammatory drugs and steroids are the drugs of choice in inflammatory episodes with continuation of antiretroviral therapy. With increasing affordability of antiretroviral therapy, clinicians will put more and more number of human immunodeficiency virus infected patients on therapy and hence an increase in the incidence of IRIS is expected. Therefore, it is important to understand all facets of this syndrome which is becoming more prevalent with each passing day. PMID- 21972658 TI - Claw-toes correction: personal technique. AB - Claw-toes deformity is quite common in leprosy because the Posterior Tibial nerve, the nerve supplying the intrinsics of the toes, is often affected. The authors present the details of technique standardized by them for correction of claw-toes of grade 1 and 2. This technique has been successfully used in 485 toes (144 patients). PMID- 21972659 TI - A study of knowledge, attitude and practices regarding leprosy among undergraduates and interns of a medical college and hospital from rural India. AB - Leprosy is an Infectious disease caused by Mycobacterium leprae and acquired through droplet infection. India has been carrying the 2/3rd global leprosy burden. Inadequate or incorrect information and knowledge about the disease and its treatment are the root causes of many stigmas and inhibitions prevalent in the various sections of the community. The present study was undertaken to assess the knowledge, attitude and practices (KAP) regarding leprosy among undergraduates (final year medical students) and interns of Rural Medical College and Pravara Rural Hospital, Loni, Maharashtra, India. It is heartening to note that most of students and interns had good knowledge about regimens, counselling and were willing to work in leprosy. There were, however, misconceptions about several aspects of diseases which were more in case of final year students compared with interns. Significant improvementin the knowledge of interns in comparison offinal year MBBS students was mostly noted on the aspects like transmission of leprosy, involvement of ulnar nerve in the leprosy, immunological relevance, use of vaccine, treatment of leprosy affected person and leprosy associated stigma. This positive change in attitudes as well as knowledge highlight the requirement of proper training and clinical exposure of medical students and important role of internship. There is need to focus on important aspects (such as cardinal signs, public health aspects and definitions, infectivity, misconception about marriage in which insignificant changes were observed. PMID- 21972660 TI - Transfer of disability care of leprosy to the affected persons and the community members. AB - Bargarh district in the western Orissa had high leprosy burden and LEPRA India supported in control activities. Its main focus was on POD care with community participation. After motivation and capacity building, it transferred the responsibility of POD care to affected persons, family, community partners and GHS staff in 2006. The effectiveness of this approach was evaluated in 2009. With personal contact responses from 112 (17%) persons with disability and 18 stakeholders were obtained. Result shows 98% affected persons are staying with family; 92% are practicing self-care; 92% felt self-care is beneficial; 57% and 36% are using commercial and MCR footwear respectively. Surgical correction of deformity is maintained in 80% of cases. Difficulty in activity and in community participation was experienced in about one third of affected persons the latter is mostly due to self stigma. The facilitators were happy with their beneficiaries. PMID- 21972661 TI - Sustainability of integrated leprosy services in rural India: perceptions of community leaders in Uttar Pradesh. AB - As part of a community-based action research to reduce leprosy stigma, village committees were formed in 3 hyper endemic states of India. From a total of 10 village committees with nearly 200 members from Uttar Pradesh, a systematic random sample of 69 men and 23 women were interviewed in-depth regarding their views on sustainability of integrated leprosy services, as currently adopted. Their recommendations were also sought for further enhancement. Percentages were computed and compared for statistical significance using the z-normal test. The findings show that less than 50% of the respondents were confident that the present trend in voluntary early reporting for MDT and management of complications was adequate to sustain the integrated leprosy services. There were no differences by men or women members and they felt that lack of proper facilities, training and orientation of staff are most influencing factors. Many suggestions were given for improving the sustainability. PMID- 21972662 TI - Public awareness on integration of leprosy services at primary health centres in Uttar Pradesh, India. AB - Leprosy services were integrated into the general health a decade ago but it seems that a majority of public are still ignorant of this development. Hence, a study was done in Uttar Pradesh, India to determine the awareness about integration and its relationships to various socio-demographic factors. A multistage representative random sample of 3000 persons was chosen in Faizabad district, selecting a sample of 3 villages each situated within 1 km, 1-3 km and beyond 3 km of a PHC. A systematic random sample of 10% of households was chosen from selected villages and an adult male and an adult female from each household interviewed by a qualified investigator. Data were computerized and cross- tabulated against distance from the PHC, sex, age, education and occupational status. Only 45.7% in Uttar Pradesh are aware of the availability of leprosy treatment facilities at PHC but most knew that MDT was free. A smaller proportion was also aware of other facilities such as ulcer dressing and treatment of complications. Family members and health workers and PHC were the main source of information. It is concluded that massive efforts are urgently needed to educate the rural public on integration. PMID- 21972663 TI - A case of leprosy with multiple cranial neuropathy mimicking Melkerson Rosenthal syndrome. AB - Involvement of cranial nerves is not uncommon in leprosy with trigeminal and facial nerves being commonly affected. Other cranial nerves can also be involved especially in longstanding cases of leprosy towards the lepromatous pole. Herein, we report a case of leprosy with multiple cranial neuropathy mimicking Melkerson Rosenthal syndrome. PMID- 21972664 TI - Type 2 lepra reaction with HIV1 co-infection: a case report with interesting management implications. AB - A patient co-infected with leprosy and Human Immunodeficiency Virus (HIV)-type 1 who developed type 2 lepra reaction in the absence of antiretroviral therapy is presented. The reaction responded only after initiating anti retroviral therapy (ART) despite normal CD4+ counts. The present report suggests that type 2 reactions in leprosy and HIV co-infected patients may not always be the typical manifestation of immune reconstitution inflammatory syndrome (IRIS) and stresses the importance of considering concomitant HIV infection in refractory lepra reactions. Extensive research is required into the manifestations of HIV in leprosy patients. PMID- 21972665 TI - The expansion of health houses and fertility outcomes in rural Iran. AB - Iran experienced a dramatic decline in fertility from 1984 to 2001, which was most rapid in rural areas. Although many attribute the decline to the government's active participation in providing family planning services, most services were provided after the initial fertility decline that took place after 1984. We assess the extent to which timing of exposure to basic healthcare is related to fertility outcomes. We estimate the association between a woman's age of exposure to a health house (clinic) and number of children, using the 2001 Iranian Household Expenditure and Income Survey and the 2006 Iranian Census, and the location and dates of operation for each rural health house. We also look at the probability of a woman's giving birth one year after a clinic opened in her village. We use Poisson and logistic multivariate regressions and we control for individual, household, and village characteristics. Exposure to a health house in a woman's most fertile years (20-34) is associated with an 18 percent decrease in number of children ever born relative to those exposed after age 40. This negative association gets progressively stronger as length of exposure increases. Our findings suggest that early exposure to health services in rural areas contributed to Iran's fertility decline. PMID- 21972666 TI - Estimating abortion incidence in Burkina Faso using two methodologies. AB - Abortion is illegal in Burkina Faso except in cases of incest, rape, fetal defect, or when the woman's life or physical health is endangered. As a result, abortion procedures are often conducted illegally and unsafely and measuring incidence proves difficult. We estimate incidence of abortion and associated morbidity using two methodologies. The first is the Abortion Incidence Complications Method (AICM), which uses information on women hospitalized for abortion-related complications as well as health professionals' assessments of the proportion of women who seek treatment for complications from unsafe abortions. The second is the Anonymous Third Party Reporting (ATPR) method, which entails surveying women about their confidantes' abortions. We conclude that the AICM yields a more accurate result. We estimate that 87,200 abortion procedures were carried out in 2008, representing 25 for every 1,000 women aged 15-49. More than one in four procedures resulted in complications treated at a health facility. The abortion rate estimated using the ATPR approach was 72 percent of that estimated with the AICM. The ATPR method yields information on the characteristics of the women who have abortions as well as the providers and methods they use. PMID- 21972667 TI - Introduction to the special section on abortion legalization in Mexico City. PMID- 21972668 TI - Patient characteristics and service trends following abortion legalization in Mexico City, 2007-10. AB - Legal abortion services have been available in public and private health facilities in Mexico City since April 2007 for pregnancies of up to 12 weeks gestation. As of January 2011, more than 50,000 procedures have been performed by Ministry of Health hospitals and clinics. We researched trends in service users' characteristics, types of procedures performed, post-procedure complications, repeat abortions, and postabortion uptake of contraception in 15 designated hospitals from April 2007 to March 2010. The trend in procedures has been toward more medication and manual vacuum aspiration abortions and fewer done through dilation and curettage. Percentages of post-procedure complications and repeat abortions remain low (2.3 and 0.9 percent, respectively). Uptake of postabortion contraception has increased over time; 85 percent of women selected a method in 2009-10, compared with 73 percent in 2007-08. Our findings indicate that the Ministry of Health's program provides safe services that contribute to the prevention of repeat unintended pregnancies. PMID- 21972669 TI - Women's experiences with legal abortion in Mexico City: a qualitative study. AB - In April 2007, elective first-trimester abortion was legalized in Mexico City. As of June 2011, more than 60,000 women from Mexico City and other Mexican states have obtained legal abortions in the city's public hospitals and health centers, with private facilities providing additional abortion services. This study examines women's experiences of abortion services in one public and two private clinic settings in 2008. Twenty-five in-depth interviews were conducted: 15 with women who obtained abortions in a public health center and 10 who obtained the procedure at either of two private clinics. Participants were highly satisfied with services at both public and private sites, although some had to go to more than one site before receiving services. None expressed doubts about their decision to have an abortion, and they felt unanimously that they were treated with respect. Furthermore, participants were pleased with the counseling they received and most accepted a contraceptive method after the procedure. PMID- 21972670 TI - Public opinion on abortion in Mexico City after the landmark reform. AB - This article presents findings from three opinion surveys conducted among representative samples of Mexico City residents: the first one immediately prior to the groundbreaking legalization of first-trimester abortion in April 2007, and one and two years after the reform. Bivariate and multivariate analyses were performed to assess changes in opinion concerning abortion and correlates of favorable opinion following reform. In 2009 a clear majority (74 percent) of respondents were in support of the Mexico City law allowing for elective first trimester abortion, compared with 63 percent in 2008 and 38 percent in 2007. A significant increase in support for extending the law to the rest of Mexico was found: from 51 percent in 2007 to 70 percent in 2008 and 83 percent in 2009. In 2008 the significant independent correlates of support for the Mexico City law were education, infrequent religious service attendance, sex (being male), and political party affiliation; in 2009 they were education beyond high school, infrequent religious service attendance, and ever having been married. PMID- 21972671 TI - Experiences and opinions of health-care professionals regarding legal abortion in Mexico City: a qualitative study. AB - This study examines the experiences and opinions of health-care professionals after the legalization of abortion in Mexico City in 2007. Sixty-four semistructured interviews were conducted between 1 December 2007 and 16 July 2008 with staff affiliated with abortion programs in 12 hospitals and 1 health center, including obstetricians/gynecologists, nurses, social workers, key decisionmakers at the Ministry of Health, and others. Findings suggest that program implementation was difficult because of the lack of personnel, space, and resources; a great number of conscientious objectors; and the enormous influx of women seeking services, which resulted in a work overload for participating professionals. The professionals interviewed indicate that the program improved significantly over time. They generally agree that legal abortion should be offered, despite serious concerns about repeat abortions. They recommend improving family planning campaigns and post-procedure contraceptive use, and they encourage the opening of primary health-care facilities dedicated to providing abortion services. PMID- 21972672 TI - Public opinion on abortion in eight Mexican states amid opposition to legalization. AB - In opposition to Mexico City's legalization of first-trimester abortion, 17 Mexican states (53 percent) have introduced initiatives or reforms to ban abortion entirely, and other states have similar legislation pending. We conducted an opinion survey in eight states--four where constitutional amendments have already been approved and four with pending amendments. Using logistic regression analyses, we found that higher education, political party affiliation, and awareness of reforms/initiatives were significantly associated with support for the Mexico City law. Legal abortion was supported by a large proportion of respondents in cases of rape (45-70 percent), risk to a woman's life (55-71 percent), and risk to a woman's health (48-68 percent). A larger percentage of respondents favored the Mexico City law, which limits elective legal abortion to the first 12 weeks of gestation (32-54 percent), than elective abortion without regard to gestational limit (14-31 percent). PMID- 21972673 TI - Abortion in Latin America: changes in practice, growing conflict, and recent policy developments. AB - Latin America is undergoing profound social, economic, political, demographic, and epidemiologic change. Reproductive health indicators have generally improved over the past two decades, but most pregnancies are still unintended and more than 4 million are terminated annually. Clandestine abortions necessitated by restrictive legal and social structures cause more than 1,000 deaths and 500,000 hospitalizations per year, primarily among poor and marginalized women. Abortions are becoming safer and less frequent, however, as a consequence of increased modern contraceptive use, misoprostol adoption, emergency contraception availability, and postabortion care provision, notwithstanding many impediments to these changes. Advocacy and conflict over abortion have grown. The contested policy shifts include Mexico City's 2007 legalization of first-trimester abortion. Drawing on numerous sources of evidence, this article provides a regional analysis of the rapidly changing practice and context of abortion in Latin America, and examines emerging issues, legal and policy developments, and contrasting country situations. PMID- 21972674 TI - Madagascar 2008-09: results from the Demographic and Health Survey. PMID- 21972675 TI - Philippines 2008: results from the National Demographic and Health Survey. PMID- 21972676 TI - [VATS in patients with solitary periferal pulmonary tumors]. AB - The patients with periferal solitary pulmonary nodule often present a serious diagnostic and therapeuthic challenge.The aim of our study is to present our experience in VATS for diagnosis and treatment of patients with solitary periferal pulmonary tumors. MATERIAL AND METHODS: For the period of 1997-2009, 146 patients with periferal pulmonary tumors underwent VATS for resection of the tumor. RESULTS: 112 (74.2%) of the patients underwent radical VATS resection of the tumor after intraoperative frozen sections for diagnosis. In the rest 39 cases (25.8%) due to different reasons VATS was converted to open thoracotomy and wedge resection. 54.55% of the resected tumors were malignant and 45.45% of them were benign. In 18 patients the intraoperative frozen sections confirmed primary lung cancer, and the procedure was converted to thoracotomy and radical resection. In 13 patients the results from the intraoperative frozen sections were not definite and we were not able to differ wether the tumor was a pulmonary metastase or a primary lung cancer, and after the final histological examination the patients were submitted to radical resection in interval. In 33 of the cases we resected pulmonary metastases from an extrapulmonary primary tumor. CONCLUSIONS: Despite the advances in diagnostic technics, only the VATS resection of the pulmonary tumor and the histological examination assures definitive diagnosis, it allows the definitive treatment for the benign lesions and indicates the correct treatment for malignant lesions. PMID- 21972677 TI - [Surgical treatment of the perianal and rectovaginal fistulas by means of Surgisis AFP anal fistula plug]. AB - Symptoms of painful and uncomfortably occurred in patients with anal and rectovaginal fistulas witch worsened their quality of life. The introduce of Biodesign Fistula Plug is called "dramatic jump in surgery of the fistulas". We can avoid from the traditionally and technicaly difficult treatment of perianal and rectovaginal fistulas through this advice. Therefore like this surgeons can avert frequently complications of the anal sphyncteric apparatus like incontinence or stenosis. We have only two cases like attempt for now but with excellent result followed up about 31 and 33 months. PMID- 21972678 TI - [Methodology of quality of life assessment with EORTC questionnaires of operated for rectum carcinoma patients. Prognostic factors]. AB - The integral psychometric term quality of life illustrates the subjective sensation of the received results. The instruments developed by EORTC contribute to its dynamic objectification and optimization, by applying the adequate practice. For patients with rectal carcinoma this marker is expected to have a prediction value, like other markers that determine the progress of the disease. PMID- 21972679 TI - [Radical nephrectomy or partial resection in localized (T1aN0M0) renal cell carcinoma]. AB - PURPOSE: To share our experience about partial resection (nephron sparing) in localized (T1aN0M0) renal hypernephroid cancer as organ preserved operation. Opportunities and longterm results. MATERIAL AND METHOD: For last 10 years we have done 89 partial resections in patients with localized renal hypernehroid cancer. In all cases we have done lymphatic dissection of relevant lymph region of the affected side. RESULTS AND DISCUSSING: All operated patients had five years of survival. We observed developing contralateral hypernefroid carcinoma in one patient that necessary performing a partial resection in this place. In two patients we performed a partial resection of a solitarykidney. The results of surgery are very good when we stage properly cancer process that allows organ preservation. PMID- 21972680 TI - [Role of IL-12P40 and IL-10 in progression of colorectal cancer]. AB - The aim of study was to investigate the association between serum levels of IL 12p40 and IL-10 and progression of the colorectal cancer (CRC). Be observed an association between severity of CRC and serum levels of investigated cytokines. IL-12p40 was in the highest level in stage-I (423.6 +/- 224.7 pg/ml) compared to more severe stages. In the opposite direction were the data for immunosuppressive cytokine, IL-10. Patients with stage-IV had the highest level of IL-10 (36.02 +/- 9.5 pg/ml). On the basis of our results we could conclude that IL-12p40 and IL-10 serum levels were associated with tumour progression. More severe stages of CRC are characterized by low IL-12p40 and high IL-10 serum levels. PMID- 21972681 TI - [The renaissance of lumbar sympathectomy]. AB - The question addressed was whether the use of sympathectomy was of benefit in non revascularisable critical leg ischaemia. Altogether 387 papers were found, of which 13 represented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses were tabulated. We conclude that lumbar sympathectomy is a minimally invasive procedure with a low complication rate. Randomized controlled trials have failed to identify any objective benefits for lumbar sympathectomy, but subjective improvements in symptoms for patients with highly symptomatic critical leg ischaemia have been consistently demonstrated in multiple cohort studies with sustained symptom improvements in approximately 60% of patients. Lumbar sympathectomy is in process of renaissance and should be considered for symptomatic patients with critical leg ischaemia as an alternative to amputation in patients with otherwise viable limbs. PMID- 21972682 TI - [Treatment possibilities in patients with glioblastoma multiforme]. AB - Glioblastoma multiforme is the most common primary malignant brain tumor in adults. The actual treatment approach includes surgical excision of the lesion followed by radio- and chemotherapy in standard doses and regimens. In most cases, in spite of aggressive treatment, the survival does not exceed 12-16 months after the initial diagnosis. The present survey provides systematic information about the current treatment modalities for control of the disease as well as the perspectives of introduction of some experimental methods in clinical practice. PMID- 21972683 TI - [Case of massive bleeding from diverticulosis of the colon in high risk mechanically ventilated patient]. AB - This 81 years old man with chronic obstructive pulmonary disease (COPD), chronic sepsis, chronic renal failure dependent on mechanical ventilation presented in the course of treatment with massive lower gastrointestinal bleeding (LGIB). Selective angiography of inferior mesenteric artery was performed 18 hours after first bleeding and localized source of bleeding at the distal colon as a contrast in the lumen of the gut. Direct intraarterial injection of 3.4 micrograms Vasopressin was carried out in inferior mesentery artery for preparation of surgery. During surgery the colonoscopy was done and despite of the high operative risk total colectomy with ileostomy was performed. This case confirms that there are not alternatives of colectomy in continuing LGIB from colonic diverticula even in the high risk patients. PMID- 21972684 TI - [Surgical treatment for intralobar pulmonary sequestration in 50-years old woman with aberrant artery from a. gastrica sin]. AB - A case of 50-years old female, operated on for intralobar sequestration with two 2 anomalous arteries in lig. pulmonale inf., one arising from thoracic aorta and the other--from truncus coeliacus of abdominal aorta. The diagnosis was confirmed by CT scan with i.v. and a left lower lobectomy was carried out with exellent long-term result. PMID- 21972685 TI - [Hepatocellular carcinoma complicated with echinococcal cyst of the liver]. AB - AIM: We present a rare case of concomitant echinococcus and hepatocellular carcinoma in a single lesion, and discuss the possible pathogenesis. MATERIAL AND METHODS: A 64-year-old woman was admitted to the hospital with a few months' history of weakness, weight loss and abdominal discomfort. Ultrasonography and computed tomography showed a cystic lesion measuring 10 cm in diameter in the segments 2 and 3 and multiple well-enhanced nodules adjacent to the cystic portion in the segments 4,5,8. RESULTS: The diagnosis was confirmed intraoperativelly--a hepatocellular carcinoma complicated with echinococcal cyst of the liver. A left trisectionectomy was performed. Mebendazole treatment was begun. CONCLUSION: The simultaneous occurrence of echinococcosis disease and hepatocellular carcinoma is quite rare. Both of these diseases are chronic processes, and this further raises the possibility that echinococcosis could have had a role in the development of the liver cancer. PMID- 21972686 TI - [Malignant melanoma of the anus and rectum]. AB - There is approximately 300 cases of malignant melanoma written in the world literature. We write up 13 operated from us for 15 years cases of melanoma of the anus and rectum. The neoplastic localization is usually at linea dentate area. The patients complains are foreign-body filling and rectohaemorrhagy. This formation considers like haemorrhoid frequently. The pain is not common symptom but ulceration occurs in many percent. The metastasing is in the inguinal lymph nodes. The tumor colour is between light-brown to red-purple in 50% of the cases. The colouring matter is absent in the other half of the cases and these tumors consider like nonpigmentous melanoes. Despite the complex treatment--surgical, chemotherapy etc. the prognosis is at large poor. PMID- 21972687 TI - [Stage of disease as a prognostic factor in radically operated patients with non small cell lung cancer]. AB - Despite the better diagnostic and therapeutic opportunities, lung cancer is still the major cause for cancer mortality. The surgical-pathological TNM-stage is known as the most reliable prognostic factor for survival in patients with lung cancer. MATERIAL AND METHODS: We present 440 patients with non-small cell lung cancer, radically operated in the Clinic of Thoracic and abdominal surgery of University Hospital "St.George" - Plovdiv for the period 01.01.1997 - 01.09.2004 378 men (85.91%) and 62 women (14.09%), age range 23-82 years. RESULTS: The mean time of survival according to the stage is as follows: IA - 77 months, IB - 67, IIA - 55, IIB - 42, IIIA - 33 IIIB - 14, IV - 27 months. CONCLUSIONS: The stage of the disease is an important prognostic factor for patients with lung cancer. We found the lowest survival in stage IIIB. For selected patients in stage IV, the operative treatment leads to good results. PMID- 21972688 TI - [Postoperative survival in patients with inoperable lung cancer]. AB - Despite the advances in treatment in the last two decades, the prognosis in lung cancer remains infavourable. Only 20-25% of the patients are suitable for operative treatment. Almost 75% of the patients are inoperable at the time of diagnosis. MATERIAL AND METHODS: We present 148 patients, who underwent non radical operation for the period 01.01.1997 - 31.12.2005 - 129 men (87.16%) and 19 women (12.84%), age range - 29-65 years (53.67 +/- 0.60). RESULTS: The mean time of survival for the group submitted to radiotherapy is 13.74 months, while for the group without postoperative radiotherapy is 9.31 months. The mean time of survival for the group submitted to chemotherapy is 9.99 months, while for the group without adjuvant chemotherapy is 10.27 months. CONCLUSIONS: The radiotherapy significantly improves the survival in the patients with inoperable lung cancer, while the chemotherapy don't increase the survival. PMID- 21972689 TI - [Extent of resection as a prognostic factor in patients with non-small cell lung cancer]. AB - Despite the new methods of treatment during the last two decades, prognosis in lung cancer remains unfavourable. Only 20-25% of the patients are suitable for surgery, and the surgical resection is the unique alternative with curable intent. The extent of resection is an important prognostic factor in lung cancer patients. MATERIAL AND METHODS: We present 440 patients with non-small cell lung cancer, radically operated in the Clinic of Thoracic and abdominal surgery of University Hospital "St.George" - Plovdiv for the period 01.01.1997 - 01.09.2004.191 underwent lobectomy, 12 - limited resection, 39 - bilobectomy, and 198 - pneumonectomy. RESULTS: 63 patients underwent lobectomy for stage I, and the 5-year survival was 63.49%. For the 12 patients with limited resection we found mean time of survival of 50 months, and the 5-year survival was 50%.331 of our patients were in stage II and III. 123 of them underwent lobectomy--the 5 year survival was 28.46%. 208 patients underwent bilobectomy and pneumonectomy- the 5-year survival in this group was 17.79%. CONCLUSIONS: In conclusion we found that the extent of resection is an important prognostic factor for lung cancer patients in stage I. The patients submitted to lobectomy have better survival compared with those submitted to limited resection. The survival is better for the group of patients who underwent lobectomy,compared with the one for the group with bilobectomy and pneumonectomy, which is probably due to the earlier stage of the disease. PMID- 21972690 TI - [Characteristics and prognosis of visual deficit caused by parasellar meningiomas]. AB - Meningiomas are the most common slow growing tumors of the central nervous system which arise from the arachnoid cells. One certain group of them--tuberculum sellae (TS), cavernous sinus (CS), anterior clinoid (AC), and planum sphenoidale (PS) meningiomas, a group often called "parasellar", present with monocular or binocular visual deterioration, which is often unrecognized by patients until visual loss is severe and the tumor has reached a significant size. AIM: To describes the type of visual deficit, severity of the symptoms and surgical treatment of tumors with the above mentioned localization. MATERIAL AND METHODS: During the period 2003-2007 year, 93 patients (31 man, 62 women) diagnosed with meningiomas of the TS (31 cases), CS (16 cases), AC (21 cases), PS (17 cases), (see text) - 8, were diagnosed and operated on in the Department of Neurosurgery, University Hospital "St. Ivan Rilsky", Sofia, Bulgaria. Retrospective analysis was done. RESULTS: Age at diagnosis ranged from 12 to 74 years, but the majority of cases were in the 5th and 6th decade of life. Localization of was: TS 33%, CS 17%, AC 24%, PS 18% and with more than one area affected in 8 %. The most common symptom was slowly progressing loss of monocular visual acuity (81% of cases). 68% of patients presented with already severely deteriorated vision (0.1-0). Neuro-ophthalmological examination (see text) the patients. Computed tomography and magnetic resonance imaging were the main diagnostic methods. "Gross" total resection was achieved in 62%, subtotal in 12%, partial in 26% of the cases. There was early improvement in 57% of the patients. Death due to cardio respiratory insufficiency occurred in one case. CONCLUSION: the progressive monocular visual deficit is often the first clinical symptom of the parasellar menigiomas. The early diagnosis is important for the success of surgery. Close collaboration between different specialists (ophthalmologists, neurologist and neurosurgeons) is essential for treatment of these tumors and prevention of the visual deterioration. PMID- 21972691 TI - [Mini-invasive approach in the treatment of acute necrotizing pancreatitis]. AB - OBJECTIVES: The study aims to evaluate the efficacy of percutaneous necrosectomy performed under ultrasound control and endoscopic necrosectomy trough secondary sinus track (ENTSST) using nephroscope and cystoscope. MATERIAL AND METHOD: Puncture of fluid collections in the pancreas was performed under ultrasonographic control to 23 patients with acute necrotizing pancreatitis (ANP). ENTSST using nephroscope and cystoscope was performed to 47 patients after open or percutaneous necrosectomy and persistent sepsis (without satellite collection of CT). RESULTS: Seventeen (74%) patients treated with percutaneous necrosectomy recovered without open surgery. Two of this group died. The average hospital stay was 42 days. Twenty-three patients required an average of two (from 1 to 4) ENTSST. CONCLUSIONS: Based on our initial results we believe that the percutaneous necrosectomy and ENTSST in well selected patients might be the better choice than the open necrosectomy and postoperative lavage. Common solution of these methods has not been reached yet. PMID- 21972692 TI - [Sepsis--current aspects]. AB - Sepsis is defined as a clinical syndrome of systemic response to infections. With progression of the disease develop organ failure (i.e. severe sepsis) and hypotension (i.e. septic shock) and mortality increases significantly. Sepsis is an interdisciplinary problem, cause significant morbidity and mortality and higher hospital costs. Deepening ofinflammation, immunity distortions, coagulation and oxygen perfusion have a major role in organ dysfunction and death. Proper diagnosis of sepsis requires an understanding of risk factors, a high index of suspicion and anatomic approach to the localization of the infectious focus. Early detection of septic patients is crucial for the outcome of disease in the application of reasoned therapy. Future treatment of sepsis associated with a better understanding of the molecular bases of pathological process. PMID- 21972693 TI - [Complications from the liver hydatidosis]. AB - Echinococcosis of the liver is widespread disease in Bulgaria. Frequently there is different complications in its development: allergies, portal hypertension, bille duct pathology, chest or nervous complications. These events frequently lead to misdiagnoses with inadequate treatment. Therefore it is necessary in case of these complains have to involve in the differential diagnosis the hydatid disease and widening indications for ultrasonography of the liver. PMID- 21972694 TI - [Ogilvie syndrome (colonic pseudo-obstruction). A case of the practice]. AB - Ogilvie syndrome, or acute colonic pseudo-obstruction (ACPO), is a clinical disorder with the signs, symptoms, and radiographic appearance of an acute large bowel obstruction with no evidence of distal colonic obstruction. The other name of this disease is an acute non-toxic megacolon. The colon may become massively dilated; if not decompressed, the patient risks perforation, peritonitis, and death. The acute state has to be discerned immediatelly and treated adequately. The conservative tactics includes naso-gastric drainage, resustitation the homeostasis and stimulation the colonic peristalsis. The aggressive behavior includes an operative treatment or colonoscopic decompression. Some authors report for considerable rising in the frequency of the cases in postoperative period in some abdominal diseases. That's why they think that Ogilvie syndrome is a postoperative disease. We present a case of the practice-- an operated man with acute colonic pseudo-obstruction (ACPO) involving acute colonic ischaemia with necrosis. PMID- 21972695 TI - [Modification of the transverse coloplasy pouch--experience with this feasible technique in different types of low rectum resections]. AB - The increased number of sphincter-spared patients after low rectal resection requires an up-to-date approach, aiming at better functional results. The authors modify into practice the transverse coloplasy pouch, with a longitudinal seromuscular incision, mucosal liberalization and transverse suture. They describe their experience with this feasible technique in different types of low rectum resections. The conception of the technique is with increased neorectal volume to avoid some unpleasant consequences of this surgery, without changing the oncological effectiveness. The modification with a single-layer suture facilitates the technique, has some advantages and does not worsen the desired effect. PMID- 21972696 TI - [40 years of renal transplantation in UMHAT "Alexandrovska"]. AB - The process of transplantation of tissues and organs, as a highly specialized treatment method, has a unique place in the field of medical science and practice. On occasion of the 40 anniversary of the first renal transplantation in adult in Bulgaria, the developments in this area are reviewed chronologically. The initial experiments on test animals, as well as the first renal transplantation in adult are described in details. For the abovementioned period 435 renal transplantations have been performed in UMHAT "Alexandrovska", 231 (53.2%) form living kidney donor and 204 (46.9%)--from cadaveric renal donors. The benefits of the existing organization of transplantation in UMHAT "Alexandrovska" are outlined, as well as the problems preventing the transplantation process to achieve even wider usage as a method for treatment of end-stage organ diseases. PMID- 21972697 TI - [Retrorectal tumors--15 years experience and literary review]. AB - PURPOSE: Tumors occurring in the retrorectal space are heterogeneous and uncommon. The utility of newer imaging techniques has not been extensively described, and operative approach is variable. This study examined the diagnosis, treatment, and outcome ofretrorectal tumors at a tertiary referral center. METHODS: Patients with primary, extramucosal neoplasms occurring in the retrorectal space were identified using a retropectively maintained, procedural database of all adult colorectal surgical patients (1995-2009). Exclusion criteria included inflammatory processes, locally advanced colorectal cancer, and metastatic malignancy. Medical records, radiology, and pathology reports were reviewed retrospectively. RESULTS: Thirty-eight patients with retrorectal tumors were treated. Malignant tumors comprised 21 percent. Older age, male gender, and pain were predictive of malignancy (P < 0.05). All benign tumors were resected with normal histologic margins and none recurred. Nine patients with malignancy had recurrence/recrudescence of their disease. CONCLUSIONS: Retrorectal tumors remain a diagnostic and therapeutic challenge. Pain, male gender, and advanced age increase the likelihood of malignancy. Various imaging modalities are useful for planning resection but cannot establish a definitive diagnosis. Whereas benign retrorectal tumors can be completely resected, curative resection of malignant retrorectal tumors remains difficult. PMID- 21972698 TI - [The analgesic efficacy of transversus abdominis plane (TAP) block]. AB - The transversus abdominis plane (TAP) block is a novel approach for blocking the abdominal wall neural afferents via the bilateral lumbar triangles of Petit. It was described for the first time in 2007 by McDonnell et al. We applied the technique after the original methodology of the authors. We evaluated its analgesic efficacy first 24 postoperative hours of patients, undergoing to surgical and urological interventions. After induction of anesthesia, 20 ml of 0.375% levobupivacaine was deposited into the transversus abdominis neuro-fascial plane via the bilateral lumbar triangles of Petit. Each patient was evaluated by VAS in the postanesthesia care unit at the 2, 4, 6, 12 and 24 h postoperatively. Despite the results were more unsatisfactory than those of McDonnel, they were good. Our first impression is that the TAP block provided highly effective postoperative analgesia in the first 24 postoperative hours after major abdominal surgery. PMID- 21972699 TI - [Adjuvant and individual application of lumbar sympathectomy at patient with arterial disease in lower limb]. AB - The first lumbar sympathectomy for treatment of arterial occlusive disease of the lower extremity was performed in 1924 by Julio Diez of Buenos Aires. The standart anatomy textbooks indicate, as a rule that the lumbar sympathetic trunk contains four or five ganglia. The overall anatomic denervation is important for achievement of an adequate sympathectomy of a given segment of an extremity. Criteria and indications for complete sympathetic block are still not clear. Exceptionally important for the improvement of the reology of the lower limbs is the option for a direct increase of the collaterals' debit which could be achieved by extensive profundoplasty. As an addition to the arterial reconstructions, the sympathectomy increases the passability of small vessel anastomosis and the recovery of traumatized arteries. Unilateral or bilateral lumbar sympathectomy is performed by retroperitonal access. From 01.01.2008 till 01.11.2008 in our clinic were performed 117 isolated and after arterial reconstruction lumbar sympathectomies. PMID- 21972700 TI - [Gunshot injuries of the ureters--retrospective study of 12 patients over 27 years period]. AB - AIM: To retrospectively study the gunshot injuries of the ureters, operated in the surgical departments of Military Medical Academy, Sofia and Medical Institute Ministry of Interior, Sofia for a period of 27 years. MATERIAL AND METHOD: The gunshot injuries of the ureters of twelve patients are retrospectively studied in the period 1980 to 2007. For all patients the localization of the injuries, urinanalysis, imaging examination results, the associated injuries, the operative procedures and complications were reviewed. RESULTS: All patients are males aged 19-28 years. Seven patients have right ureteral injuries and five have left ureteral inuries. In three patients the urinanalysis is normal, five have microscopic and four have gross hematuria. The injury is located in the proximal third of the urether for six patients, in four it is in the mid and in another two in the the distal ureter. Complications are registered in 40% of the cases. CONCLUSIONS: Due to the high ratio of false negative results from the urinanalysis and the imaging studies, careful and precise exploration of the retroperitoneum in order no to omit a possible injury of the ureters. PMID- 21972701 TI - [External carotid endarterectomy]. AB - Noneoperative treatment of the internal carotid artery (ICA) occlusion is associated with increased recurrent stroke rates. Several randomized trials have validated the use of carotid endarterectomy (CEA) to treat symptomatic internal carotid artery occlusions. The aim of this study is to analyze the data from external CEA for treatment of symptomatic ICA occlusions, to evaluate its safety and outcomes. MATERIAL AND METHODS: 302 surgical interventions on the carotid artery in 295 patients had been operated for 42 months (from January 2006 to June 2009) at the "Department of Vascular Surgery and Angiology" of "St. Ekaterina" University Hospital --Sofia. 30 patients were with symptomatic ICA occlusion, and in 17 of them we used external carotid endarterectomy. The patients had been analyzed according to the type of surgical intervention and clinical picture. The frequency of postoperative complications and outcomes had been investigated. RESULTS: There were no complications in the early postoperative period. We found reduction or disappearing of the neurological signs in the patients. On the 30th day after the surgery patients were without any clinical symptoms. There were no restenosis or reoclusions at the postoperative check up. No patients died in the perioperative period (30 days). CONCLUSION: The restoration of the ICA blood flow reduce the risk of recurrent strokes, which is demonstrated in the long term follow up. External carotid endarterectomy (ECA) is estimate procedure for relieving the hemispheric symptoms in patients with ICA occlusions. PMID- 21972702 TI - [Prognostic value of estrogen receptors--ERalpha and ERbeta, in patients with lung cancer]. AB - SUMMARY: There are over 150 prognostic factors in lung cancer, which allow to predict the outcome of the disease.Many molecular factors are known to have independent prognostic significance. At present these factors are not routinely used in the clinical practice, but they may play an important role in the future for precise individual prognosis. MATERIAL AND METHODS: The study included 122 patients with non-small cell lung cancer.Using immunohistochemistry we examined the expression of estrogen receptors--ERalpha and Erbeta. RESULTS: The median time of survival depending on the expression of Eralpha was 31 months, while for Erbeta was 73 months. CONCLUSIONS: Erbeta is a positive prognostic factor in patients with non-small cell lung cancer. PMID- 21972703 TI - [Prognostic value of the molecular markers ICAM-1 and C-JUN in patients with lung cancer]. AB - Many of the clinical and fundamental scientific studies are directed to the investigation of the prognostic factors in patients with lung cancer. Many molecular factors are known to have independent prognostic significance and although these factors are not routinely used in the clinical practice, they may play an important role in the future. MATERIAL AND METHODS: The study included 122 patients with non-small cell lung cancer. We examined the expression of ICAM 1 and C-Jun. RESULTS: The median time of survival for the group with poor expression of C-Jun was 39 months, and 26 months for the group with strong expresssion. The median time of survival for the group with poor expression of ICAM-1 was 51 months and only 9 months for the group with strong expresssion. CONCLUSION: The increased levels of ICAM-1 and C-Jun are negative prognostic factors for the patients with non-small cell lung cancer. PMID- 21972704 TI - [Cysts of the mammary gland--surgical behavior and treatment]. AB - The goal of the current article is to point the role of the different methods of surgical behavior in cases of mammary gland formations which have been ultrasonographically and mammographically diagnosed as cysts. Thirty-four women, clinically, ultrasonographicaly and mammographicaly diagnosed with cysts, are taken under consideration. Fine needle biopsy is carried out in all of the cases and the cysts' contents are cytologically and microbiologically tested. In 16 of the cases, puncture followed by pneumatocele represents the definitive treatment. In the end of the puncture, a control mammography is performed. Eighteen of the patients undergo surgical treatment due to the density of the cysts' contents, presence of bloody discharge, presence of a bilocular cyst and relapse following the puncture. As a result of the surgical treatment of 18 patients and of the histology are found as follows: benign cysts (13), carcinoma (1), papilloma (1), sclerotic adenosis (1), ADH (1), epidermoid cyst (1). PMID- 21972705 TI - [The role of matrixmetalloproteinases in the tumor growth and metastasis]. AB - Many authors have described the role ofmatrixmetalloproteinases (MMP) in tumor invasion. MMPs are a family of zinc-dependent endopeptidases, which through degradation of the extracellular matrix (ECM) and the basal membrane induce tumor spread and metastasis. There are more than 20 enzymes classified into 6 groups: Collagenases (MMP-1,-8,-13 and -18), Gelatinases (MMP-2 and MMP-9, Stromelysins (MMP-3,-7,-10,-11,-26,-27), Elastases (MMP-12), Membrane type specific MMPs (MMP 14,-15,-16,-17,-24 H -25) and other MMPs (MMP-19,-20,-28,-21,-22,-23). Many authors have demonstrated a positive correlation between the pattern of MMP expression and the tumor invasive and metastatic potential including: rectal and gastric cancer, lung carcinoma, breast, ovarian, prostate, thyroid cancer and brain tumors. The increased expression of tissue inhibitors of MMPS (TIMPs) is a response against the tumor progression leading to suppression of the MMP-activity and preservation of the ECM integrity. Due to the dual role of TIMPs, which together with MT1-MMP activate pro-MMPs it is possible that the correlation between activator/inhibitor is the one defining the tumor growth and metastasis. PMID- 21972707 TI - [Problems of the specialization in surgery in European union and in the world]. PMID- 21972706 TI - [Endovascular or surgical treatment of the carotid arteries]. AB - Ischemic stroke is the third most common cause of death right after myocardial infarction and malignancies. Most cases of stroke are due to extracranial carotid atherosclerotic disease. The percutaneous transluminal angioplasty and stenting of the carotid arteries have emerged as an alternative to the standart carotid endarterectomy mainly because they are less invasive procedures. Carotid stenting with or without the use of neuroprotection devices proves to be effective in high risk patients with carotid stenosis. Nevertheless, there is no clear proof that endovascular techniques outmatch the classic surgical methods. PMID- 21972708 TI - [Solid pseudopapillary pancreatic tumor (tumor of Gruber-Frantz)]. PMID- 21972709 TI - [Late metastases from breast cancer--report of two cases]. AB - INTRODUCTION: Breast cancer is amongst the commonest reasons for brain metastases involving 15-20% of the patients. Metastases discovered 10 or more years after the initial diagnosis of breast cancer are defined as late metastases and present a rare event. We present two cases of late brain metastases of breast cancer discovered 15 and 17 years after initial diagnosis. MATERIALS AND METHODS: In a 46-year old female patient a 5 x 6 cm lesion in the breast was observed and was histologically diagnosed to be a breast invasive ductal carcinoma. Mastectomy was performed (TNM grade - T2N1bM0) with postoperative radiotherapy (40 Gy for 20 days) combined with chemotherapy. All control investigations were normal for the next 17 years. During the last examination CA-15-3 levels were raised. CT scan revealed a lesion involving the frontal, temporal and parietal bones and the adjacent soft tissues as well as dura mater and the subdural space. Gross total resection was performed. In a 38-year old female patient a 3 cm lesion in the breast was observed and was histologically diagnosed to be a low differentiated invasive ductal breast carcinoma. Radical mastectomy was performed TNM grade (T2N1M0) with radio- and chemotherapy. For 13 years all control markers were negative. Last examination demonstrated increase of CA-15-3 levels. Due to complain of headache and nausea CT scan was performed showing a tumor lesion in the right frontal lobe. Gross total resection was performed. CONCLUSION: In the presented cases we describe late brain metastasis from breast cancer 15 and 17 years after initial diagnosis. This observation is important because, regular followup for patients with breast cancer is 6-10 years. Obviously this approach in clinical practice could lead to mistakes and misdiagnosis of these rare lesions. Based on our experience we suggest that the follow-up, in patients treated for breast cancer, even with apparently total regression of the disease, should be extended beyond the routine period of 10 years and tumour markers should be investigated regularly. Metastasis in CNS should be taken into consideration in patients treated for breast cancer no matter the time from the initial diagnosis when clinical symptoms appear. PMID- 21972710 TI - [Operative technique for the oesophago-jejunostomy after gastrectomy for the cancer of the stomach]. AB - Author's described operative technique for the oesophagojejunostomy after gastrectomy for the cancer of the smonach. We are making antireflux termino lateral oesophago-jejunostomy with antiperistaltic including proximal parts of the jejunum and distal parts of the duodenum, and with subcolic dextromesenterial propulsive latero-lateral duodeno-jejunostomy. PMID- 21972712 TI - [Contemporary organ preserving surgical approaches in the breast cancer treatment]. AB - The contemporary approach in breast surgery conduct organ preserving operations like preferable from surgeons and patients more and more. The reconstructive organ preserving and plastic operations are cosmetic with esthetic benefit and also oncologically radical. The local recurrences are in the same percent comparing the radical mastectomy. We report 48% quadrantectomies and 52% mastectomies for 2009. PMID- 21972711 TI - [The role of surgical treatment of primary non-small cell lung cancer with synchronous brain metastases]. AB - Although several studies confirm the superiority of surgical resection of the primary lung cancer and metachronous brain metastases to other treatment modalities, the results of resection of the primary non-small cell lung cancer and synchronous brain metastases are still controversial. MATERIAL AND METHODS: In the clinic of Thoraco-abdominal surgery of the University Hospital "St.George" for the period 01.01.1997-01.09.2004 radically operated are 440 patients with non small cell lung cancer, 6 of them had solitary brain metastases, succefully resected in clinic of neurosurgery. RESULTS: We found 5-year survival in only 1 of the patients, the mean survival for the rest of them was 16 months. CONCLUSIONS: Although the overall survival for the patients with non-small cell lung cancer and brain metastases is poor, the surgical resection may be beneficial in a select group of patients without lymph node metastases. PMID- 21972713 TI - [Prognostic value of the molecular markers cyclin D1 and P53 in patients with lung cancer]. AB - The discovery of new genes with important regulatory functions on cellular level, allowed the investigation of many biological and molecular changes and defining their value as potential prognostic factors. MATERIAL AND METHODS: The study included 122 patients with non-small cell lung cancer. We examined the expression of cyclin D1 and p53. RESULTS: The 5-years survival rate was 26% for the group with strong nuclear expression of cyclin D1, and 80% for the group with moderate expression of the marker. We found 5-years survival rate of 100% for the group with poor expression of p53, and 24.55% for the group with strong expression. CONCLUSIONS: The increased levels of cyclin D1 and p53 are negative prognostic factors for the patients with non-small cell lung cancer. PMID- 21972714 TI - [Nipple-sparing mastectomy (subcutaneal mastectomy with preserving of the areolomammilar complex) like alternative of the modify radical mastectomy in selected cases]. AB - INTRODUCTION: In the last ten years breast's surgery changed significantly. The different types mastectomy which conserve the skin and the halo and nipple are more and more popular. From oncology's point of view this kind of operations show similar results compared with the classical modified radical mastectomy, but they have significantly advantage to imrove the final aesthetic result and to reduce the psychological stress of surgery intervention for the patient. Our main goal is to make survey of medical data and to prove oncological radicality and reconstructive efficiency of nipple-sparing mastectomy (NSM) with one-moment reconstruction. MATERIALS AND METHODS: In period 2006-2009 in our clinic to 52 patients with breast cancer or with high risk of occurrence is done NSM and one moment reconstruction with prothesis or expander. Of this number five patients are operated bilateral. We selected patients with small to medium size breasts and tumor to 3 sm, distant at least 2 sm from NSM. On a stable preparation in two cases (3.8% of all cases) is established invasion of retro-mamilarian tissue with tumor cells which indicated excision of NSM on second stage. This cases are not included in our study. The adjuvant therapy is conducted in indications according with approved standards. RESULTS: After 2-36 months period monitoring non of the patients showed local relapse. One of them (1.75%) receive distant metastases and died. Necrosis of NSM is observed in 13 patients (22.9%) and in all ot these cases it was partial and it was contained with conservative methods. In one case only (1.75%) the patient reported significant change in sensitivity of NSM. The final aesthetic result was evaluated subjectively of the patients and their doctors as very good or excellent in majority of cases. CONCLUSION: Our results are similar with established from other collegues and support the thesis that conserve NSM with one-moment reconstruction is oncologycally justified operation which conserve the patients in good psychological condition, improving the quality of life and it's reasonable alternative of MRM in similar cases. PMID- 21972715 TI - [Assessment of the surgical approaches in liver hydatid disease]. AB - Surgery has major role in liver echinococcosis. Different types of operation techniques are being analyzed in the complicated and uncomplicated forms of the disease. The less traumatic closed methods are preferred, as the best results have been the modified operation of Lagro and Coria by bonding the veil with BTG on fibrous plate. In the yeast echinococcosis with best result has been the half closed method with permanent lavage of the residual cavity. Different complications and behavior have been interpreted. There are offers in the surgery of the uncomplicated echinococcosis to introduced resection of the convex dome with application through pulverization of tissue glue on the remaining fibrosis. Theoretical advantages proved this method. PMID- 21972716 TI - [What is the value of ERCP in the era of MRCP?]. AB - INTRODUCTION: The diagnostic approach in patients suspicious for gallstone disease is represented by two main methods--ERCP and MRCP. The magnetic resonance cholangio-pancreatography is safe and precise method of imaging diagnostics, while the endoscopy combines both good diagnostic and therapeutic possibilities. MATERIALS AND METHODS: 223 patients were enrolled, 68 of theme were with diagnosed cholestasis and endoscopic sphincterotomy, which was therapeutic in 53 cases. In all patients this condition has been diagnosed using MRCP--in 51 cases choledocholithiasis was diagnosed; 11 were with tumor obstruction; in 6 cases no mechanical cause was found. ERCP was performed on 62 patients with following therapeutical sphincterotomy. RESULTS: All 223 with performed cholecystectomy were with rate of conversion of 3% and hospital stay--3 days. There were no cases of pancreatitis after the sphincterotomy or hemorrhages requiring hemotransfusion. CONCLUSION: Algorithm including MRCP with performing endoscopic sphincterotomy is safe and effective in the diagnostic and treatment of choledocholithiasis. MRCP can be applied in addition to ERCP and IOC. PMID- 21972717 TI - [Enzymology of the liver in hydatidosis]. AB - A research has been conducted studying the enzyme system of the liver using biopsy material of the organ taken during the operation from patients with echinococcosis and an experiment with infantile white mice. It is proved reduction of the activity of the alkaline and acid phosphatase as well as of the glycogen along with their progressive reduction during the disease progression. Compared with the other researches--histological and by electronic microscope, etc.--there are proved great hepatic damages due to the echinococcosis that have caused change of the treatment tactics: large preoperative period, including reconstructions of the glycogenic depot in the organ, gentle to the liver anesthesia, exact postoperative reanimation. Very good results have been obtained concerning the postoperative complications and operative mortality: observing the developed acute liver insufficiency--in the past the mortality has been 27.60% throughout 2.49% of the operated patients; after those measures the acute liver insufficiency after this kind of operation is seen just once (0.40% of the patients) and the mortality is 0. PMID- 21972718 TI - [Complex results of investigating the quality of life after rectal surgery]. AB - INTRODUCTION: The recent development of rectal surgery is related to the possibility of avoiding permanent stoma formation, which is presumably believed to be the main factor that decreases quality of life. Despite the modern views of the disease, the adequacy of complex treatment and the technical improvements, low anastomoses often result in poor bowel function. The subjective perception of health is changed for these patients. There arises the question of adequacy of operative approach. The aim of our investigation was analysis of the present QoL data of patients treated in the Specialized Oncology Hospital of Veliko Tarnovo. MATERIALS AND METHODS: The quality of life of 173 patients was examined with the help of EORTC questionnaires QLQ C30 and QLQ C38. The comparison is between a group with high anterior resection (N1 = 50-28.9%), a group with low sphincter sparing operation (N2 = 59-34.3%) and primary extirpated patients (N3 = 53 30.8%). They were questioned preoperatively, in an early and late aspect, as well as before prophylactic stoma closure. RESULTS: The high resected patients present the best QoL values. Performing the extirpation leads to significant preoperative drop and a good adaptation afterwards. Their indexes are not much different from anterior resection group. Compared with the low technique group considerable improvement as regards the scales social functioning and global health status (P < 0.05) was observed. This group has high values of general and specific symptomology (pain, constipation, diarrhea, dyspnoea, financial difficulties, defecational problems and sexual dysfunction) generating low QoL. Their recovery is prolongated in relation with the drop of the modules before the prophylactic stoma closure. CONCLUSION: The best health perception available after treating the rectum carcinoma is for high located tumors. We recon that for patients with extirpation techniques and primary stoma formation there is no objective data of QoL decrease. In comparison, the group with low rectal resections had to undergo another operative intervention, and there were some specific complications and following poor function reducing quality of life. The requirement for very precise selection of patients must be fulfilled. PMID- 21972719 TI - [Surgical hygroscopic bandages for amputations, secreting wounds and diabetes foot]. AB - The authors adopt in clinical practice using of sterile hygroscopic wound dressings 'pampers type'. They use these dressings in 113 patients. The appropriate patients are these with limbs amputations, diabetic foot, suppurative and plenty secreting deep wounds, atonite and decubital wounds. The dressings are sterilised using paraformaldehyde sterilization which do not injure the synthetic materials. The hygroscopic dressings are non- allergic and are well tolerated by the patients. Using these dressings facilitate the medical team work and help to reduce the contamination of the hospital linen and the patients coverlet. They help for accelerating the wound healing process. They are also economic effective by reducing the amount of used dressing material. PMID- 21972720 TI - [Therapy of extracranial carotid artery aneurysms--literature review]. AB - Extracranial carotid artery aneurysms are unusually rare. Their aetiology and clinical picture have significant meaning for their recognition, with the majority involving the common carotid artery--ACC. Approximately one third of these lesions are confined to the ICA, with an equal distribution between the proximal, middle, and distal segments. Nonoperated treatment is associated with a high risk of stroke compare to surgical, wich is think as necessary from most authors, because of the high level of neurologic symptomatic in the studies. Surgical treatment is used for prevention from cerebrovascular deficit. PMID- 21972721 TI - [Microbiological aspects and antibiotic treatment of abdominal gunshot injury]. AB - Abdominal gunshot injury is a life-threatening condition that requires urgent and complex measures: control of hemorrhage and source of infection through a surgical intervention; prophylaxis and antibiotic therapy of the infectious complications; intensive care for cardiology and pulmonary support. First phase in infection process (diffuse peritonitis and bacteremia), is governed by Escherichia coli, Enterococcus spp, Bacteroides fragilis group, while the second (development of abscess)--by anaerobes. Application of antibiotic prophylaxis or therapy depends on the time since the incidence together with the score evaluating severity of patient'status. Empiric antibiotic therapy should be broad spectrum and rapidly bactericidal. PMID- 21972722 TI - [Abdominal TB. Peritonitis due to perforated intestinal TB & upper intestinal fistulas. Surgical treatment]. AB - Nowadays tuberculosis--TB is most popular chronic infections disease in the world. The mortality is high, 3 million approximately death every year in the world. TB affects predominantly the lungs (pulmonary--90%) and exra-pulmonary) skin; bones; joints; urinary tract-UT; gastro intestinal tract-GIT; abdominal TB. There is an increase in diagnosed cases of pulmonary TB last years in Bulgaria. There are very rare cases of diagnosed abdominal TB described. We present a case operated from us in Multi Pro File Hospital Cherven Bryag. A 54 years old male patient with peritonitis due to perforated intestinal TB and upper intestinal fistulas. The patient was not aware of suffering from pulmonary TB in the past. PMID- 21972723 TI - [A rare case with excessive congenital arterio-venous angiodysplasy of the upper extremity]. AB - The congenital vascular anomalies of an upper extremity are rare, but may cause serious complications during them development and haemodynamic. We present a case of one patient with congenital arterio-venous malformation of the right arm and fore-arm, advanced and progressed by impossible level of an operation or invasive treatment. The changes in the venous system are with obligate predisposition for dyabrosis, rupture and profuse bleeding from the extremity. The problems by the complex treatment of the congenital arterio-venous vascular diseases are considerable, in spite of all that the lower frequency and manifest expression to them, in particular in the cases with polyorgans comorbidity. PMID- 21972724 TI - [Necrotizing fasciitis--a clinical case with a review of literature]. AB - Necrotizing fasciitis is a life-threatening dermatosis with an acute clinical course. It represents a severe soft tissue dermal-hypodermal infection of polymicrobic nature. Often it is complicated by systemic deterioration, multi organ dysfunction and lethal outcome. Herein, a clinical case of an immunocompetent patient with necrotizing fasciitis of the lower extremity is presented. A short overview of the recent achievements in diagnostic verification and therapeutic approaches of the disease is laid out. PMID- 21972725 TI - ["The lower, the better:" this was not confirmed in the risk/benefit report of the ACCORD trial]. PMID- 21972726 TI - [Assessment and management of aortic stenosis]. AB - Surgical aortic valve replacement is the sole validated treatment of aortic stenosis. The indications for surgery rely on risk/benefit ratio and on the official recommendations. A symptomatic patient with severe aortic stenosis should be submitted to surgery. The indication of valve replacement is more difficult in asymptomatic patients. The decision should integrate a combination of an exercise test and prognostic parameters associated with poor outcome. Most of them are obtained by Doppler echocardiography. Patients presenting with severe aortic stenosis and low transvalvular gradient constitute a subgroup of patients who require appropriate echocardiographic assessment to determine the potential benefit and risk of surgery. Transluminal aortic valve implantation is a new modality for patients at high surgical risk. PMID- 21972727 TI - [Type 2 diabetes and anti-inflammatory agents: new therapeutic prospects?]. AB - It is now well accepted that a chronic, low-grade inflammation is observed in abdominal obesity, insulin resistance and type 2 diabetes mellitus, and that pro inflammatory cytokines and oxidative stress play a role in the pathogenesis of type 2 diabetes. These new findings raise the question of whether antiinflammatory strategies may have a place in the prevention and treatment of type 2 diabetes. This review article describes the results obtained in studies on patients with metabolic syndrome or type 2 diabetes aiming to test the metabolic effect of anti-inflammatory (salicylates, antagonists of interleukine-1, antagonists of tumor necrosis factor-alpha) and anti-oxydants (succinobucol) drugs. PMID- 21972728 TI - [Renal SGLT2 inhibitors, new agents for the management of type 2 diabetes]. AB - Kidney plays a role in glucose homeostasis, not only by its capacity to produce glucose through local gluconeogenesis, but also, and even more important in presence of diabetes, by its capacity to excrete glucose in urine when hyperglycaemia exceeds tubular reabsorption threshold. Such reabsorption depends on sodium-glucose cotransporters-2 (SGLT2), which can be blocked by selective inhibitors. These pharmacological agents augment glucosuria and reduce hyperglycaemia independently of insulin. Some have already proven their efficacy to improve glucose control, in monotherapy or in combination, while promoting weight loss and without inducing hypoglycaemia. Dapagliflozin should be the first medication of this new pharmacological class to be commercialized for the management of type 2 diabetes. PMID- 21972729 TI - [Hypophosphatemia and tumor-induced osteomalacia]. AB - In this article, we will discuss about hypophosphatemia due to tumor-induced osteomalacia. This disease is characterized by severe muscular and articular tenderness inducing profound walking limitation. Clinical chemistry results show severe hypophosphatemia due to hyperphosphaturia. Fibroblast growth factor 23 (FGF-23) is abnormally high. Physiological role of FGF-23 is examined. We also consider the pathophysiology of tumor induced osteomalacia, the use of different investigations to localize the tumor and therapies available to treat this rare disease. PMID- 21972730 TI - [Current management of myelodysplastic syndromes]. AB - Treatment of myelodysplastic syndromes (MDS) has improved in recent years with better results of allogeneic stem cell therapy (SCT), the advent of new therapeutic options such as hypomethylating agents and lenalidomide, the introduction of iron chelation therapy and the implication of erythropoietic stimulating agents in the treatment of anemia. In this review, we summarize the different diagnostic and prognostic criteria and outline the different treatment options we have in 2011. PMID- 21972731 TI - [Mantle cell lymphoma: management in 2011]. AB - Mantle cell lymphoma is a rare form of non Hodgkin lymphomas. Diagnosis is made by demonstrating a typical immunophenotype as well as the presence of a translocation between chromosomes 11 and 14 with overexpression of cyclin D1. First line therapy for young patients consists in 3 cycles of "R-CHOP21" alternated with 3 "R-DHAP21" and followed by an autograft conditioned by total body irradiation, cyclophosphamide and aracytine. For patients over 65 years of age, the treatment of choice consists in 8 cycles of "R-CHOP21". Maintenance treatment is under evaluation. Allografting is the only chance of cure in relapsed patients with good performance status. Targeted therapies will improve the prognosis of this disease. PMID- 21972732 TI - [AIDS mortality in Switzerland: its characteristics and its impact on overall mortality]. AB - The AIDS epidemic has transformed not only the mortality at some younger ages, but also the perception of the needs in health that we may have, since the rapid spread of HIV/AIDS, coupled with a prognosis fatal disease until the mid-1990s. The eyes of demography, here allows to highlight the characteristics of AIDS mortality in Switzerland, and changes the pattern of mortality that Switzerland experienced by AIDS. The author also suggests, drawing on traditional demographic tools, a method to attempt to measure the impact of AIDS mortality on life expectancy at birth in Switzerland. A parallel with the analysis of mortality from tumors reinforces the importance of the impact of AIDS mortality. PMID- 21972733 TI - [From the epigenome to the exposome]. PMID- 21972734 TI - [Reflexions on some predispositions]. PMID- 21972735 TI - [AIDS and its progression in homosexuals of the Middle East and North Africa]. PMID- 21972736 TI - [The very edifying adventure of Dr. Bonnemaison (1)]. PMID- 21972737 TI - [Guardian angels]. PMID- 21972738 TI - [Maintaining the quality of nursing care]. PMID- 21972739 TI - [The law of nursing care without consent published but still disputed]. PMID- 21972740 TI - [Repeated transcranial magnetic stimulation, an innovative experience]. PMID- 21972741 TI - [Rethinking the management of addictions]. PMID- 21972742 TI - [An alarming portrait of patients and nurses in psychiatry]. PMID- 21972743 TI - [Day hospital in question]. PMID- 21972744 TI - [The day hospital in search of its identity]. AB - After more than fifty years of existence, the day hospital remains a little known tool. Submerged in the new psychiatric landscape, between part time therapeutic care centres, home hospital care and mutual support groups, this institution, which offers appropriate care, finds itself being questioned with regard to its place, its development and its future. PMID- 21972745 TI - [The psychiatric day hospital network, an area of reflection and action]. AB - Created in Belgium forty years ago, the Psychiatric day hospital network today brings together professionals from across the world to reflect on institutional psychotherapy. Beyond the protocols, this approach places the human being at the heart of the care process. PMID- 21972746 TI - [The Adamant, an unusual care centre]. AB - The day care centre of the central Paris area has established itself in an unusual location--a 650 m2 floating building moored on the right bank of the Seine. Patients and caregivers were involved in the design of this original and ecological care centre, which places the emphasis on comfort and safety. PMID- 21972747 TI - [A healing atmosphere]. AB - The day hospital of Abbeville is a building located in the town center, where the atmosphere is more important than prescriptions. The case of a patient in his thirties shows the role of this place, at the meeting point of other psychiatric care structures. This organization is permitted by the specific organization of the French psychiatrical sector, with a work orientation aimed towards care and shared by a team. PMID- 21972748 TI - [Night hospital, a complementary form of care]. AB - In child psychiatry, part time night hospitalisation is an alternative which complements other forms of care such as day hospitals. In Saint-Cyr-au-Mont-d'Or, the development of these night stays is the outcome of a joint reflection carried out over several years. PMID- 21972749 TI - [Bibliography]. PMID- 21972750 TI - [Training future nurses in providing care for patients who committed criminal acts]. AB - Providing care for patients who have carried out criminal acts is a source of questioning for caregivers, who must position themselves in this specific care relationship. For three years, the nursing training institute (IFSI) in Orthez has offered students an optional module in criminology. Through discussions and critical reflection, its aim is to enable future nurses to be better prepared. PMID- 21972751 TI - [Failure of a mourning ritual and reactive depression]. AB - In some African societies, mourning rituals are a way of isolating death from the territory of the living and to allow the bereaved to regain, after a certain time, their place in society. However, for a young educated woman confronted with the brutal death of her sister, the traditional ritual to which her family subjected her resulted in a prolonged reactive depression combined with cognitive disorders.. PMID- 21972752 TI - [The general practitioner faced with somatoform disorders]. AB - Functional pain pathology is a public health issue, due to its prevalence, the costs it generates and the disability it causes the patient. The role of general practitioners is crucial. They must avoid the pitfall of pointless, sometimes dangerous, examinations and treatments, and seek to create with the patient a long-lasting and good quality relationship, key to the treatment of these disorders. PMID- 21972754 TI - Evolution in testing technology enables some urban EDs to implement HIV screening at relatively low cost. AB - Despite strong recommendations from the CDC for EDs and other health care settings to implement routine screening for HIV, only a minority of EDs offer HIV screening programs. However, new testing platforms that enable high-volume, laboratory-based blood tests with a reasonable turnaround time for results, are enabling a number of hospitals in urban areas to implement HIV screening for a relatively low cost. Ben Taub General Hospital in Houston now performs opt-out screening for all ED patients who require a blood draw for any reason. Since this testing program began in 2008, Ben Taub has identified 780 patients as HIV positive, and most of these patients had been to the ED multiple times previously without becoming aware of their disease status. The approach has enabled Ben Taub to lower the cost of HIV screening from $77 per test to about $12 per test. Ben Taub uses service linkage workers to connect patients identified as HIV positive with appropriate resources for care. PMID- 21972753 TI - [Jean-Baptiste Pussin]. PMID- 21972755 TI - Take steps to curb violence, improve safety for ED personnel. AB - While violent eruptions are well documented in the ED, there is a not a lot of research into what strategies are most effective at both curbing violence and managing incidents when they do occur. Experts suggest that ED managers should consider staff training and visible security measures when developing procedures for dealing with violence. In one survey of ED physicians, more than three quarters reported at least one incident of workplace violence in the previous 12 months. Researchers report that many EDs post security at the point of entry, but lack security coverage in patient care areas. Experts suggest that verbal de escalation techniques can be helpful in lowering anxiety levels.They also urge ED managers to bring in assistance when the ED is crowded or waiting times are long. PMID- 21972756 TI - CT use more than triples in the ED, but use of the technology may be linked with a significant drop in hospitalizations. AB - A new study shows that use of computed tomography (CT) scanning has exploded in the ED in recent years, despite high-profile concerns regarding patient exposure to radiation. The retrospective study, which looked at CT use in the ED from 1996 to 2007, suggests that use of the technology grew by 330% during the study period. However, the study suggests that the increase in CT use may be linked with a significant decrease in hospitalization following the use of CT.The rate of hospitalization following a CT went from 26% in 1996 to 12.1% in 2007. However, experts remain concerned that more needs to be done to curb excessive use of CT. In fact, the Joint Commission has issued a Sentinel Event Alert, urging hospitals to implement safeguards with respect to CT scans. Potential targets for improvement include use of CT for flank pain, head injury, neck injury, and pulmonary embolism; experts say evidence-based guidelines suggest alternative diagnostic approaches in these cases. Peer review of testing patterns may help to curb excessive CT use, but experts say ED managers and emergency physicians need to come up with new strategies to address the problem. PMID- 21972757 TI - High-tech approach to medication reconciliation saves time, bolsters safety at hospital in northern Virginia. AB - Clinicians in the ED at Alexandria Inova Hospital in Alexandria, VA, have been able to streamline the medicine reconciliation process with the help of a new high-tech tool that retrieves a patient's medication history in a matter of minutes and transforms the data into a form that can automatically populate the patient's electronic medical record.The approach is facilitated by the regional health information exchange (HIE) organization, and will eventually be available to other providers in northern Virginia. Thus far, 80% to 90% of patients who have come through the ED have consented to have their medication history electronically retrieved. Eventually, administrators anticipate that the same approach will be used to share patient radiology studies, laboratory results, and other patient information across providers. Experts predict this practice will be commonplace among U.S. hospitals within five years, but they encourage hospital and ED administrators to take advantage of opportunities to leverage regional HIEs. PMID- 21972758 TI - Clinically relevant basic science models. PMID- 21972759 TI - Correction of moderate to severe coronal plane deformity with the STAR ankle prosthesis. AB - BACKGROUND: Prior studies have demonstrated a correlation between the degree of preoperative coronal plane deformity and failure following ankle replacement. We reviewed all of our patients who underwent ankle replacement utilizing the STAR prosthesis from 2000 to 2009 to evaluate the outcome of those with moderate (10 to 19 degrees) and severe (20 degrees or greater) coronal plane deformity. MATERIALS AND METHODS: Out of 130 consecutive patients, 43 patients had at least 10 degrees of preoperative coronal plane deformity. Twenty-five ankles had 10 to 19 degrees degrees of deformity and 18 ankles had 20 degrees or greater deformity. Average age was 66 years. Average length of followup was 41 (range, 12 to 98) months. RESULTS: Average talar preoperative deformity was 17.9 (range, 10 to 29) degrees, while average initial talar postoperative deformity was 3.5 (range, 0 to 12) degrees. Average final talar postoperative deformity was 4.7 (range, 0 to 14) degrees. Preoperative and final correction of deformity was statistically significant (p < 0.01), but there was no significant difference between initial and final postoperative correction. Overall, recurrence of the preoperative coronal plane deformity occurred in six of 43 patients (14%). All three patients who had deformities over 25 degrees developed recurrences. Correction of the coronal plane deformities was achieved by using intraoperative soft-tissue balancing, including deltoid ligament release in 12 patients and lateral ligament reconstruction in one patient. Deltoid ligament release was found to be necessary for all patients with greater than 18 degrees of varus plane deformity. CONCLUSION: Correction of moderate to severe coronal plane deformity with the STAR prosthesis was achievable with only soft-tissue balancing procedures with predictable results especially for deformities less than 25 degrees. PMID- 21972760 TI - Incidence of plantar lateral foot pain before and after the use of trial metal wedges in lateral column lengthening. AB - BACKGROUND: One of the major concerns with lateral column lengthening (LCL) in symptomatic flatfoot deformity treatment is the risk of postoperative plantar lateral foot discomfort. We evaluated whether this risk can be minimized by using trial metal wedges. Using our study's evaluation tools, the incidence of postoperative plantar lateral foot discomfort before and after using trial metal wedges was determined. MATERIALS AND METHODS: The incidence of planter lateral foot pain after LCL was retrospectively assessed in 122 consecutive patients (132 feet) after they had undergone flatfoot reconstruction with LCL between 2001 and 2007. To determine if the incidence could be reduced, levels of pain or revision were compared before and after the use of trial metal wedges. The ratio of wedge size to preoperative radiographic calcaneal length was also determined. RESULTS: The overall incidence of plantar lateral discomfort was 11.2%. The incidence of pain or revision was lower after the introduction of trial metal wedges (6.3% compared to 14.7%), but did not reach significance (p = 0.084). There was no significant difference found in the ratio of the size of bone graft wedge to calcaneal length between the two groups (p = 0.805). CONCLUSION: The incidence of plantar lateral foot discomfort overall was 11.2% after LCL. We believe this risk may be reduced using trial metal wedges, properly judging eversion stiffness and carefully assessing the position of the foot intraoperatively. PMID- 21972761 TI - The use of the Lapidus procedure for recurrent hallux valgus. AB - BACKGROUND: The objective of this study was to evaluate the Lapidus procedure or it's modifications for treatment of recurrent hallux valgus (HV). Our hypothesis was that the Lapidus procedure would achieve good correction of recurrent HV and patients would be satisfied. MATERIALS AND METHODS: A retrospective review of 32 feet (30 patients) treated with the Lapidus procedure for recurrent HV with at least 1-year followup was performed. Evaluation included radiographs, examination, and chart review. Outcomes were assessed with a pain visual analog scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) hallux score, SF 12, Revised Foot Function Index (RFFI), and a survey. Twenty-three of 30 patients (25 feet) met the criteria for inclusion in the study and were available for followup evaluation. The average followup was 31.6 months. RESULTS: Arthrodesis was present in 24 out of 25 feet (96%). The time from initial HV correction to revision surgery was 91 months. The initial surgery performed was a distal osteotomy (15), proximal osteotomy (five), exostectomy (two), diaphyseal osteotomy (two), and proximal/distal osteotomy (one). Preoperative evaluation revealed 96% of patients had clinical hypermobility of the first TMT joint and 52% had radiographic findings of instability. The average postoperative AOFAS hallux score was 82.8, SF-12 score was 94.5, and RFFI was 101. The average preoperative hallux valgus angle (HVA), intermetatarsal angle (IMA), and distal metatarsal articular angle (DMAA) were 36.2, 13.6, 18.6 degrees, respectively, which corrected to an average of 15.2, 7.5, 11.7 degrees postoperatively (p < 0.001). The average shortening of the first ray was 2.9 mm. Average pain VAS was 2.4. Eighty-seven percent reported good to excellent results. Using a multivariable linear regression analysis, postoperative HVA along with change in length of the first ray were significant predictors of quality of life based on SF-12 (p < 0.05). CONCLUSION: The Lapidus procedure corrected recurrent HV with a low nonunion rate and excellent radiographic correction and patients were satisfied with their outcome. LEVEL OF EVIDENCE: IV, Retrospective Case Series PMID- 21972762 TI - Outcomes following pantalar arthrodesis in rheumatoid arthritis. AB - BACKGROUND: We report a consecutive series of pantalar arthrodeses in patients with rheumatoid arthritis, using a single laterally based incision and autologous bone graft. MATERIALS AND METHODS: All operations were performed by a single surgeon and were assessed preoperatively and at 6 and 12 months postoperatively. The levels of patient satisfaction, functional improvement and pain scores of the foot following surgery were recorded along with radiological parameters. Seventeen patients (two male and 15 female) underwent 18 hindfoot surgeries and were assessed preoperatively using the SF-12 General Health survey questionnaire, Manchester-Oxford Foot Survey and pain scores. RESULTS: We found a significant improvement in pain levels and SF-12 scores. In addition the patients reported a high level of satisfaction with the outcome of surgery and improvement in function. CONCLUSION: The results show that pantalar arthrodesis is a very effective operative treatment for severe ankle and concomitant hindfoot disease. The treatment period is prolonged and patients should be counselled appropriately. LEVEL OF EVIDENCE: IV, Retrospective Case Series PMID- 21972763 TI - The slot graft technique for foot and ankle arthrodesis in a high-risk patient group. AB - BACKGROUND: High rates of arthrodesis nonunion have been described in the ankle, hindfoot and midfoot in patients with significant risk factors. The purpose of this study was to evaluate fusion rates, risk of reoperation, postoperative pain scores and patient satisfaction for a slot graft inlay arthrodesis technique used in a high-risk group of foot and ankle patients. MATERIALS AND METHODS: We retrospectively reviewed all ankle, hindfoot and midfoot arthrodeses by two foot and ankle surgeons in our institution between January 2000 and January 2009. Seventeen arthrodesis procedures in 16 patients using the slot graft technique were identified. Patient charts were reviewed for medical history, risk factors, previous surgery and postoperative complications. Time to union was evaluated on radiographs. Patients provided final followup by phone with an assessment of pain, overall satisfaction and use of orthotic or assistive devices. RESULTS: Union occurred in 13 arthrodesis procedures (77%) with an average time to union of 5 months. Postoperative infection occurred in one patient. Additional surgery was performed in nine patients. At final followup patients reported low pain scores (3 of 10) and high satisfaction (8 of 10). Fourteen of 15 patients contacted indicated that they would choose to undergo the procedure again. CONCLUSION: The slot graft arthrodesis technique provided satisfactory results in this small group of patients with a low complication rate. Patient satisfaction rates were high with low pain scores at an average of 62 months postoperatively. PMID- 21972764 TI - Alignment of ankle and hindfoot in early stage ankle osteoarthritis. AB - BACKGROUND: Supramlleolar osteotomy has been recommended to correct varus deformity of the tibial plafond, however we have seen only a few ankles with significant deviation of alignment in early stage osteoarthritis, in which realignment treatments might be necessary to modify the course of the disease. Our hypothesis was that there are diverse radiographic features of the tibial plafond and hindfoot in varus ankle osteoarthritis. MATERIALS AND METHODS: The study included 154 ankles of 98 patients with medial osteoarthritis, and 80 ankles of 80 normal subjects. On weightbearing AP radiographs, the tibial anterior surface angle (TAS), tibial axis-medial malleolus angle (TMM) and talar tilt angle was measured. On weightbearing lateral radiographs, tibial lateral surface angle (TLS) was measured. On the hindfoot alignment view, the heel alignment angle and heel alignment ratio were obtained. Inter- and intraobserver reliabilities were obtained for all radiographic parameters. The radiographic parameters were compared among the normal ankles and the ankles in different stages of ankle arthritis by the Takakura classification. RESULTS: Inter- and intraobserver reliability were very high for all radiographic parameters except TLS. There was no statistically significant difference in TAS among stages 2, 3a, and 3b. TAS was 86.9 +/- 2.4 degrees, 86.2 +/- 3.3 degrees, and 85.4 +/- 4 3.1 degrees in stage 2, 3a, 3b, respectively. There was no significant difference in hindfoot alignment among normal, stage 2, stage 3a. The hindfoot alignment angle was 0.5 +/- 8.1 degrees, 0.5 +/- 6.8 degrees, and 9.6 +/- 9.1 degrees in Stage 2, 3a, 3b, respectively. CONCLUSION: Alignment of the tibial plafond and hindfoot was variable in early stage ankle osteoarthritis. LEVEL OF EVIDENCE: III, Retrospective Case Control Study PMID- 21972765 TI - Perfusion pressures and distal oxygenation in individuals with diabetes undergoing chronic hemodialysis. AB - BACKGROUND: The number of diabetic patients worldwide was estimated to be approximately 285 million in 2010. Approximately 5% of all diabetic patients have foot ulcers, often preceded by neuropathy and delayed healing resulting from peripheral vascular disease which leads to increased risk of infection. Additionally, there is a concern that blood flow to the feet may be reduced in patients with diabetes, which may be further compounded by changes in lower extremity perfusion pressure during hemodialysis. Current laser Doppler technology provides the opportunity to identify changes in vascularityin a non invasive fashion. MATERIALS AND METHODS: A prospective, parallel-arm, comparison, pilot study was conducted. A total of 15 patients were enrolled, ten of whom had a documented history of diabetes. All patients required hemodialysis. Peripheral perfusion and oxygenation measurements were obtained before, midway and at the conclusion of three separate dialysis sessions within a 3-week interval for each subject. RESULTS: Preliminary results indicate a significant reduction in toe pressure during and after hemodialysis in the diabetic patient group compared to the non-diabetic group. Significant differences were not found in skin perfusion measurements or in the oxygenation measurements at any time in diabetic and nondiabetic patients undergoing hemodialysis. CONCLUSION: Preliminary results suggest hemodialysis may significantly affect pressure of the lower extremities in diabetic patients. Trends from these data indicate the need to further investigate the effect of hemodialysis on techniques used to heal wounds and ulcers in patients with diabetes. PMID- 21972767 TI - Fore- and rearfoot kinematics in high- and low-arched individuals during running. AB - BACKGROUND: Differences in the location and incidence of lower extremity injuries have been reported between high and low arched individuals. These differences might be related to functional differences between the two foot types. In particular, the characteristics of the medial longitudinal arch may influence foot function. The purpose of this study was to investigate forefoot and rearfoot kinematics as well as tibial shock in participants with both high and low arches. MATERIALS AND METHODS: Fifteen high arched and 15 low arched males were recruited. Tibial acceleration as well as forefoot, rearfoot and shank kinematic data were collected as participants ran at 3.5 m/s wearing gait sandals. Variables of interest included peak tibial acceleration in addition to rearfoot eversion excursion, forefoot eversion excursion, forefoot eversion velocity, forefoot abduction excursion and forefoot abduction velocity. MANOVA and effect sizes were used to investigate kinematic differences between groups. RESULTS: Multivariate analysis revealed that foot type had an effect on the kinematic variables of interest (p = 0.04). Forefoot abduction excursion (High arched = 4.7 +/- 1.3 degrees, Low arched 3.8 +/- 1.0 degrees) and forefoot abduction velocity (High arched = 96.0 +/- 24.8 degrees/s, Low arched = 69.3 +/- 13.3 degrees/s) were greater in the high arched group. Tibial shock (p = 0.24) and other kinematic variables were similar between groups. CONCLUSION: Clear evidence of forefoot and rearfoot motion as a shock attenuation mechanism was not found. Differences in the foot kinematics during early stance were highlighted by a smaller forefoot abduction excursion and reduced forefoot abduction velocity in low arched compared to high arched individuals. It is suggested that low arched feet may have a reduced available range of motion through which the forefoot can pass before reaching the end range of motion point. CLINICAL RELEVANCE: Foot kinematics during early stance warrant further investigation to establish a specific link to injury risk. PMID- 21972766 TI - Locked versus nonlocked plate fixation for hallux MTP arthrodesis. AB - BACKGROUND: Dorsal plate fixation is used commonly for arthrodesis of the hallux first metatarsophalangeal (MTP) joint. Custom dorsal plates incorporating locking technology have been developed recently for applications in the foot to provide relative ease of application and theoretically superior mechanical properties. The purpose of this study is to compare the radiographic and clinical outcomes of patients undergoing hallux MTP joint arthrodesis using a locked plate, or a nonlocked plate. MATERIALS AND METHODS: We compared consecutive patients who underwent hallux MTP arthrodesis for a variety of diagnoses with either a precontoured locked titanium dorsal plate (Group 1) or a precontoured, nonlocked stainless steel plate (Group 2). All patients were evaluated with radiographs, visual analog pain scale, American Orthopaedic Foot and Ankle Society (AOFAS) hallux score, and a detailed patient satisfaction survey. RESULTS: There were 73 feet in Group 1 and 107 feet in Group 2. There was a trend toward a higher nonunion rate in Group 1 compared to Group 2. When considering only patients without rheumatoid arthritis (RA), the union rate was significantly higher in Group 2 compared to Group 1. Hardware failure and the overall complication rate was equivalent between the two Groups. CONCLUSION: As locked plate technology continues to gain popularity for procedures in the foot, it is important that clinical outcomes are reported. Locked titanium plates were associated with higher nonunion rates. Improved plate design, patient selection, and an understanding of plate biomechanics in this unique loading environment may optimize future outcomes for hallux MTP arthrodesis. PMID- 21972768 TI - Tophaceous pseudogout of the ankle: case report. PMID- 21972769 TI - Avulsion fracture of the dorsal talonavicular ligament: a subtle radiographic sign of possible Chopart joint dislocation. PMID- 21972770 TI - Arthroscopic treatment of impingement after total ankle arthroplasty: technique tip. PMID- 21972771 TI - Whole length flexor hallucis longus transfer with a minimally invasive approach: technique tip. PMID- 21972772 TI - Tourniquet application on the difficult thigh: technique tip. PMID- 21972773 TI - FootForum: payer panels and device access. PMID- 21972774 TI - Without a past there is no future: Berson and Yalow-reminiscences. PMID- 21972775 TI - The impact of microRNAs on endocrinology. AB - The endocrine system controls various cellular functions, constitutes a communication network between cells and distant tissues, and is vital for maintaining homeostasis. The couriers of this system are the hormones, which are produced by endocrine cells, secreted into the bloodstream and interact with receptors to exert their effect. The regulatory effect is manifested by either activating signaling cascades or by altering transcription patterns. Though thoroughly examined, many aspects of the endocrine system's function are still unclear. MicroRNAs (miRNAs) are short (approximately 22nt), non-coding RNAs that comprise a new subset of cellular regulatory molecules. MiRNAs regulate gene expression post-transcriptionally, by base pairing with the messenger RNA's (mRNA) 3' untranslated region (3'UTR). In recent years, miRNAs have emerged as key players in all cellular processes, and their aberrant expression has been linked with different types of disease and malignancies. This review focuses on the role of miRNAs in the function of the endocrine system, emphasizing the intricate reciprocal relationship between these two important regulatory systems. PMID- 21972776 TI - Growth hormone therapy: emerging dilemmas. AB - The history of pituitary growth hormone (GH) started 100 years ago but the isolation purification and determination of the chemical structure of the human GH (hGH) took another 50 years. Starting in 1957 hGH was extracted from cadaver pituitaries and its clinical use was restricted to severe GH deficient patient. With the invention of recombinant biosynthetic hGH in 1985; the indications for its use were extended. The major approved medications are GH deficiency and short statured children of various etiologies. This is a critical review of present and future use of human GH. To evaluate the effectiveness of the hGH treatment several pharmaceutical companies established postmarketing follow-up programs which are based on the reliability and cooperation of the treating physicians. Unfortunately they stop when the treatment is terminated and most studies refer to growth stimulation effectiveness during initial years but do not follow the children until final height. The long-term experience enabled to evaluate adverse effects (AE), the majority being due to large dosage. The most serious AE reported are increases in malignancies and early or late mortality in adult age. There is consensus that GH deficient children need replacement therapy. As long term hGH treatment is expensive and the final height gains in non-GH deficient children small the cost-benefit indications to treat short children without a disease has been questioned. To avoid the need of daily injections, long-acting hGH preparations undergo clinical trials. The future will show their effectiveness and eventual adverse effects. PMID- 21972777 TI - Molecular mechanisms underlying insulin-like growth factor action: How mutations in the GH: IGF axis lead to short stature. AB - Insulin-like growth factors (IGFs) act via the Type 1 IGF receptor (IGF-1R) to promote growth and development. Recent structural and site-directed mutagenesis studies have provided detailed insight into the mechanism of interaction between the IGFs and the IGF-IR. Studies of the insulin: insulin receptor interaction have provided important additional understanding of the mechanisms underlying the IGF:IGF-1R interaction. The recent crystal structure of the insulin receptor ectodomain showed a folded over conformation accommodating two potential ligand binding pockets. The ligand interacts with the receptor at two different sites within a binding pocket to achieve high affinity binding and activation of the receptor. In this review the effect of mutations in the human IGF1 and IGF-1R genes so for reported are explained in terms of the effect on ligand binding and receptor activation. The severity of patient phenotype can generally be correlated to the effect of the mutation on protein structure and function. PMID- 21972778 TI - IGFBP-2 at the interface of growth and metabolism--implications for childhood obesity. AB - The growth hormone/insulin-like growth factor-I (IGF-I) axis is at the centre of normal human childhood growth. Six well characterised binding proteins (IGFBP-1 to IGFBP-6) act as general carriers of IGF-I, but they also modulate IGF-I bioavailability and activity in a tissue-specific, and developmentally appropriate, manner. Recent findings also point to several binding proteins possessing specific 'lGF-independent' actions and, in particular, there is now substantial evidence linking IGFBP-2 with nutritional status and insulin sensitivity. IGFBP-2 concentrations are reduced in obesity, and further reductions are seen in those with Type 2 diabetes. As IGFBP-2 is the major IGFBP expressed in infancy, and is also the predominant IGFBP produced from adipocytes, it is ideally positioned to act as a keystone between nutrition, growth and metabolism. Childhood obesity is associated with an increased risk of long-term morbidity and mortality, but the factors that determine which obese children will develop these long-term complications are not fully understood. IGFBP-2 may be integrally involved in the molecular processes that govern the development of obesity and subsequent weight-related disease. Within this manuscript, we explore the associations between IGFBP-2 and obesity with a particular emphasis on how an increased understanding of the role of IGFBP-2 in metabolism may lead to improvements in the prevention and treatment of childhood obesity. PMID- 21972779 TI - The pygmy short stature enigma. AB - The Pigmy populations of Central Africa are known as the shortest human populations worldwide showing an endocrine profile similar to Caucasian individuals with idiopathic short stature. Therefore, the study of these subjects may significantly improve our knowledge of the mechanisms regulating normal growth in humans. In this review we summarize the existing knowledge on Pygmies' short stature, including evolutionary hypothesis, studies on their GH/IGF-I axis and their immune system functioning. We illustrate in depth our recent studies on the ethnic group of Pygmies called Babinga, living in the forest of Cameroon, suggesting that the size of Pygmy subjects is reduced from birth, compared to a neighbouring population, and that it is associated with reduced GH and GH receptor gene expression. These results provide a research target for future epigenetic investigations and suggest that the short stature of African Pygmies is probably determined by complex genetic systems. PMID- 21972780 TI - 8th Annual World Congress in Insulin Resistance, Diabetes & Cardiovascular Disease, November 4-6, 2010. PMID- 21972781 TI - Resolution and mass range performance in distance-of-flight mass spectrometry with a multichannel focal-plane camera detector. AB - Distance-of-flight mass spectrometry (DOFMS) is a velocity-based mass-separation technique in which ions are separated in space along the plane of a spatially selective detector. In the present work, a solid-state charge-detection array, the focal-plane camera (FPC), was incorporated into the DOFMS platform. Use of the FPC with our DOFMS instrument resulted in improvements in analytical performance, usability, and versatility over a previous generation instrument that employed a microchannel-plate/phosphor DOF detector. Notably, FPC detection provided resolution improvements of at least a factor of 2, with typical DOF linewidths of 300 MUm (R((fwhm)) = 1000). The merits of solid-state detection for DOFMS are evaluated, and methods to extend the DOFMS mass range are considered. PMID- 21972782 TI - Spectroscopic and electronic structure studies probing covalency contributions to C-H bond activation and transition-state stabilization in xanthine oxidase. AB - A detailed electron paramagnetic resonance (EPR) and computational study of a key paramagnetic form of xanthine oxidase (XO) has been performed and serves as a basis for developing a valence-bond description of C-H activation and transition state (TS) stabilization along the reaction coordinate with aldehyde substrates. EPR spectra of aldehyde-inhibited XO have been analyzed in order to provide information regarding the relationship between the g, (95,97)Mo hyperfine (A(Mo)), and (13)C hyperfine (A(C)) tensors. Analysis of the EPR spectra has allowed for greater insight into the electronic origin of key delocalizations within the Mo-O(eq)-C fragment and how these contribute to C-H bond activation/cleavage and TS stabilization. A natural bond orbital analysis of the enzyme reaction coordinate with aldehyde substrates shows that both Mo?S pi -> C H sigma* (DeltaE = 24.3 kcal mol(-1)) and C-H sigma -> Mo?S pi* (DeltaE = 20.0 kcal mol(-1)) back-donation are important in activating the substrate C-H bond for cleavage. Additional contributions to C-H activation derive from O(eq) lp -> C-H sigma* (lp = lone pair; DeltaE = 8.2 kcal mol(-1)) and S lp -> C-H sigma* (DeltaE = 13.2 kcal mol(-1)) stabilizing interactions. The O(eq)-donor ligand that derives from water is part of the Mo-O(eq)-C fragment probed in the EPR spectra of inhibited XO, and the observation of O(eq) lp -> C-H sigma* back donation indicates a key role for O(eq) in activating the substrate C-H bond for cleavage. We also show that the O(eq) donor plays an even more important role in TS stabilization. We find that O(eq) -> Mo + C charge transfer dominantly contributes to stabilization of the TS (DeltaE = 89.5 kcal mol(-1)) and the Mo O(eq)-C delocalization pathway reduces strong electronic repulsions that contribute to the classical TS energy barrier. The Mo-O(eq)-C delocalization at the TS allows for the TS to be described in valence-bond terms as a resonance hybrid of the reactant (R) and product (P) valence-bond wave functions. PMID- 21972783 TI - Short hydrogen bond between redox-active tyrosine Y(Z) and D1-His190 in the photosystem II crystal structure. AB - The crystal structure of photosystem II (PSII) analyzed at a resolution of 1.9 A revealed a remarkably short H-bond between redox-active tyrosine Y(Z) and D1 His190 (2.46 A donor-acceptor distance). Using large-scale quantum mechanical/molecular mechanical (QM/MM) calculations with the explicit PSII protein environment, we were able to reproduce this remarkably short H-bond in the original geometry of the crystal structure in the neutral [Y(Z)O...H...N(epsilon)-His-N(delta)H...O?Asn] state, but not in the oxidized states, indicating that the neutral state was the one observed in the crystal structure. In addition to the appropriate redox/protonation state of Y(Z) and D1 His190, we found that the presence of a cluster of water molecules played a key role in shortening the distance between Y(Z) and D1-His190. The orientations of the water molecules in the cluster were energetically stabilized by the highly polarized PSII protein environment, where the Ca ion of the oxygen-evolving complex (OEC) and the OEC ligand D1-Glu189 were also involved. PMID- 21972784 TI - What moves a family doctor to specialise in HIV? Interviews with Australian policy key informants. AB - The population of people living with HIV in Australia is increasing, requiring an expert primary care workforce to provide HIV clinical care into the future. Yet the numbers of family doctors or general practitioners (GPs) training as community-based HIV medication prescribers may be insufficient to replace those retiring, reducing hours or changing roles. We conducted semi-structured interviews between February and April, 2010, with 24 key informants holding senior roles in organisations that shape HIV-care policy to explore their perceptions of contemporary issues facing the HIV general practice workforce in Australia. Informed by interpretive description, our analysis explores how these key informants characterised GPs as being 'moved' by the clinical, professional and political dimensions of the role of the HIV general practice doctor. Each of these dimensions was represented as essential to the engagement of GPs in HIV as an area of special interest, although the political dimensions were often described as the most distinctive compared to other areas of general practice medicine. Our analysis explores how each of these dimensions contributes to shaping the contemporary culture of HIV medicine and suggests that such an approach could be useful for understanding how health professionals become engaged in other under-served areas of medical work. PMID- 21972785 TI - Lesbian and bisexual women's human rights, sexual rights and sexual citizenship: negotiating sexual health in England. AB - Lesbian and bisexual women's sexual health is neglected in much Government policy and practice in England and Wales. This paper examines lesbian and bisexual women's negotiation of sexual health, drawing on findings from a small research project. Themes explored include invisibility and lack of information, influences on decision-making and sexual activities and experiences of services and barriers to sexual healthcare. Key issues of importance in this respect are homophobic and heterosexist social contexts. Drawing on understandings of lesbian, gay and bisexual human rights, sexual rights and sexual citizenship, it is argued that these are useful lenses through which to examine and address lesbian and bisexual women's sexual health and related inequalities. PMID- 21972786 TI - Masculinity and male sexual behaviour in Mozambique. AB - Like many countries in sub-Saharan Africa, Mozambique is facing a severe HIV epidemic. Evidence suggests that male sexual behaviour is one of the driving forces behind the epidemic. Yet, there is limited understanding of how notions of masculinity influence such behaviour in the context of HIV. Using data collected through focus group discussions and in-depth interviews with sexually active men and women, this paper investigates how notions of masculinity influence the risk of HIV infection among men. The study findings suggest that traditional norms of masculinity, the man as the main provider and figure of authority, continue to exert a strong influence on male attitudes and behaviour. Alternative approaches are urgently needed in HIV programming that take into consideration notions of masculinity in order to reduce risky sexual behaviour. PMID- 21972788 TI - Site, rate, and mechanism of photoprotective quenching in cyanobacteria. AB - In cyanobacteria, activation of the Orange Carotenoid Protein (OCP) by intense blue-green light triggers photoprotective thermal dissipation of excess absorbed energy leading to a decrease (quenching) of fluorescence of the light harvesting phycobilisomes and, concomitantly, of the energy arriving to the reaction centers. Using spectrally resolved picosecond fluorescence, we have studied cells of wild-type Synechocystis sp. PCC 6803 and of mutants without and with extra OCP (DeltaOCP and OverOCP) both in the unquenched and quenched state. With the use of target analysis, we managed to spectrally resolve seven different pigment pools in the phycobilisomes and photosystems I and II, and to determine the rates of excitation energy transfer between them. In addition, the fraction of quenched phycobilisomes and the rates of charge separation and quenching were resolved. Under our illumination conditions, ~72% of the phycobilisomes in OverOCP appeared to be substantially quenched. For wild-type cells, this number was only ~29%. It is revealed that upon OCP activation, a bilin chromophore in the core of the phycobilisome, here called APC(Q)(660), with fluorescence maximum at 660 nm becomes an effective quencher that prevents more than 80% of the excitations in the phycobilisome to reach Photosystems I and II. The quenching rate of its excited state is extremely fast, that is, at least (~240 +/- 60 fs)(-1). It is concluded that the quenching is most likely caused by charge transfer between APC(Q)(660) and the OCP carotenoid hECN in its activated form. PMID- 21972789 TI - Complications associated with peripheral or central routes for central venous cannulation. AB - We undertook a review of studies comparing complications of centrally or peripherally inserted central venous catheters. Twelve studies were included. Catheter tip malpositioning (9.3% vs 3.4%, p = 0.0007), thrombophlebitis (78 vs 7.5 per 10,000 indwelling days, p = 0.0001) and catheter dysfunction (78 vs 14 per 10,000 indwelling days, p = 0.04) were more common with peripherally inserted catheters than with central catheter placement, respectively. There was no difference in infection rates. We found that the risks of tip malpositioning, thrombophlebitis and catheter dysfunction favour clinical use of centrally placed catheters instead of peripherally inserted central catheters, and that the two catheter types do not differ with respect to catheter-related infection rates. PMID- 21972790 TI - Polyorchidism with varicocele: a case report and review of literature. AB - Polyorchidism is defined as the presence of more than 2 histologically proven testes. We report the case of a 20-year-old man with polyorchidism, presenting with right scrotal pain and right scrotal ovoid mass. Scrotal examination revealed two ovoid, mobile lumps with testicular sensation in the right side of the scrotum. Scrotal colour Doppler ultrasonography and magnetic resonance imaging confirmed the presence of double testes with common epididymis and common vas. Microscopic varicocele ligation was performed, and then, two ipsilateral testes were sutured together. The testes were then returned to the scrotum with fixation. PMID- 21972791 TI - Quantification of p-phenylenediamine and 2-hydroxy-1,4-naphthoquinone in henna tattoos. AB - BACKGROUND: Very few studies are available in which the components of henna products used by tattoo artists have been analysed. OBJECTIVE: The aim of this study was to quantify the amounts of lawsone (2-hydroxy-1,4-naphthoquinone, the active ingredient in henna) and p-phenylenediamine (PPD) in products used by tattoo artists and in commercial henna preparations used as hair dyes or to create temporary tattoos. METHODS: We used high-performance liquid chromatography to detect and quantify lawsone and PPD concentrations in three products used by henna tattoo artists, 11 commercially available henna preparations, and a batch of henna leaves (Lawsonia inermis). RESULTS: The henna leaves contained 1.85 1.87% lawsone. Only one of the three preparations used by tattoo artists contained lawsone (0.21-0.35%), and all three were adulterated with PPD (1-64%). Of the 11 commercial henna preparations analysed, nine contained lawsone (1-2%) and two contained PPD (2% and 12%). CONCLUSIONS: Products purporting to be henna, but that in fact contain no henna, are being offered. Moreover, these products may contain PPD, which is associated with health risks, especially severe allergic reactions. PMID- 21972792 TI - Effects of ions on the solubility transition and the phase-separation of N isopropylacrylamide in water. AB - The effects of NaCl, NaOH, and HCl on the solubility transition and the phase separation of N-isopropylacrylamide (NIPA) were investigated for the purpose of clarifying the physicochemical mechanism of salting-out and salting-in phenomena. The discrete change in the solubility of NIPA in the salt-free water at the solubility transition (reported in J. Phys. Chem. B 2010, 114, 14995-15002) decreased with the addition of HCl and disappeared in the HCl solutions at concentrations higher than 2 M, while it increased with additions of NaOH and NaCl. A difference in NIPA concentration between the phase-separated solutions decreases with the addition of HCl and increases with additions of NaOH and NaCl. Partition coefficients of HCl in the phase-separated NIPA-rich solutions are higher than those in the NIPA poor solutions, while partition coefficients of NaCl and NaOH between the NIPA-rich and -poor solutions have trends opposite to those of HCl. The present results clearly indicate that the HCl favors the dehydrated NIPA and stabilizes the H(2)O-poor state of the NIPA molecule more than NaCl. PMID- 21972793 TI - Segmentation of virus particle candidates in transmission electron microscopy images. AB - In this paper, we present an automatic segmentation method that detects virus particles of various shapes in transmission electron microscopy images. The method is based on a statistical analysis of local neighbourhoods of all the pixels in the image followed by an object width discrimination and finally, for elongated objects, a border refinement step. It requires only one input parameter, the approximate width of the virus particles searched for. The proposed method is evaluated on a large number of viruses. It successfully segments viruses regardless of shape, from polyhedral to highly pleomorphic. PMID- 21972794 TI - Mad-honey intoxication confirmed by pollen analysis. AB - CONTEXT: Despite numerous publications showing rhythm disturbance and hypotension caused by mad-honey intoxication, none of the findings are associated with ischemic heart disease. CASE DETAILS: A 48-year-old patient was admitted to emergency service with acute anterior wall myocardial infarction after ingestion of mad-honey. Stent was implanted to the 99% stenosis lesion in the mid-portion of left anterior descending coronary artery. In this case, pollen analysis showed the suspected honey heavily contaminated with Rhododendron species pollen. DISCUSSION: Mad-honey intoxication cases often apply to emergency service with similar signs and symptoms of acute coronary syndrome; therefore it may cause acute coronary syndrome to be bypassed. This also shows that in the cases of mad honey intoxication, suspected honey pollen and/or toxin analysis should be done to confirm the diagnosis of mad-honey intoxication. PMID- 21972795 TI - Aspects of reproductive ecology of Clusia valerioi Standl. and Clusia peninsulae Hammel (sp. nov.), two Central American species of Clusiaceae with resin flowers. AB - Clusia valerioi Standl. and C. peninsulae Hammel, sp. nov. (formally established in the Appendix), two Central American species of Clusiaceae offering resin as a floral reward, were studied in the Piedras Blancas National Park, SW Costa Rica. Basic data on phenology, flower structure, course of anthesis, flower visitors, flower visitation and pollination processes, fruit development and seed dispersal are communicated. Resin collection and pollen release are reported and documented in greater detail. The significance of stingless bees for pollination is confirmed, but honeybees were also observed to visit the flowers and to collect resin. The seeds of C. valerioi, exhibiting a clearly ornithochorous character syndrome, were observed to be eaten and dispersed by four species of the tanager family (Thraupidae) and one species of finch (Fringillidae). Ants were also observed to carry away the seeds. PMID- 21972796 TI - Evaluation of anodic behavior of commercially pure titanium in tungsten inert gas and laser welds. AB - PURPOSE: This study evaluated the resistance to corrosion in welds made with Tungsten Inert Gas (TIG) in specimens made of commercially pure titanium (cp Ti) in comparison with laser welds. MATERIALS AND METHODS: A total of 15 circular specimens (10-mm diameter, 2-mm thick) were fabricated and divided into two groups: control group-cp Ti specimens (n = 5); experimental group-cp Ti specimens welded with TIG (n = 5) and with laser (n = 5). They were polished mechanically, washed with isopropyl alcohol, and dried with a drier. In the anodic potentiodynamic polarization assay, measurements were taken using a potentiostat/galvanostat in addition to CorrWare software for data acquisition and CorrView for data visualization and treatment. Three curves were made for each working electrode. Corrosion potential values were statistically analyzed by the Student's t-test. RESULTS: Statistical analysis showed that corrosion potentials and passive current densities of specimens welded with TIG are similar to those of the control group, and had lower values than laser welding. TIG welding provided higher resistance to corrosion than laser welding. CONCLUSION: Control specimens welded with TIG were more resistant to local corrosion initiation and propagation than those with laser welding, indicating a higher rate of formation and growth of passive film thickness on the surfaces of these alloys than on specimens welded with laser, making it more difficult for corrosion to occur. PMID- 21972798 TI - Pain in amyotrophic lateral sclerosis: a population-based controlled study. AB - BACKGROUND AND PURPOSE: To assess the prevalence and characteristics of pain in an epidemiological series of patients with amyotrophic lateral sclerosis (ALS) compared to population-based controls. METHODS: Of the 183 patients with ALS resident in the province of Torino, Italy, 160 accepted to be interviewed. Controls were randomly selected from the lists of general practitioners. Pain was assessed using the Brief Pain Inventory. RESULTS: Patients with ALS reported pain more frequently than controls [91 (56.9%) vs. 53 (33.1%); P = 0.001]. Pain frequency and intensity were correlated with a worse functional score and a longer disease duration. In patients with ALS, pain was more frequently located at the extremities (P = 0.006). Pain interfered with all areas of daily function, but patients reported a greater interference than controls in the domains of enjoyment of life and relation with other people. Sixty-four patients (70.3% of those with pain) and 24 controls (45.3% of those with pain) (P = 0.003) were treated for pain, most frequently with non-steroidal anti-inflammatory drugs. ALS cases were also more frequently prescribed non-opioid analgesics and opioids than controls. CONCLUSIONS: Our study indicates that pain is frequent in all stages of ALS, but that it often goes underrecognized and undertreated. It is significantly more frequent in patients with ALS than in population-based controls. Future studies need to clarify the mechanisms of pain in ALS and determine the most effective treatment strategy. PMID- 21972797 TI - Relative contribution of perception/cognition and language on spatial categorization. AB - This study investigated the relative contribution of perception/cognition and language-specific semantics in nonverbal categorization of spatial relations. English and Korean speakers completed a video-based similarity judgment task involving containment, support, tight fit, and loose fit. Both perception/cognition and language served as resources for categorization, and allocation between the two depended on the target relation and the features contrasted in the choices. Whereas perceptual/cognitive salience for containment and tight-fit features guided categorization in many contexts, language-specific semantics influenced categorization where the two features competed for similarity judgment and when the target relation was tight support, a domain where spatial relations are perceptually diverse. In the latter contexts, each group categorized more in line with semantics of their language, that is, containment/support for English and tight/loose fit for Korean. We conclude that language guides spatial categorization when perception/cognition alone is not sufficient. In this way, language is an integral part of our cognitive domain of space. PMID- 21972799 TI - Pollen limitation and inbreeding depression in an 'old rare' bumblebee-pollinated grassland herb. AB - Habitat fragmentation and reduction of population size have been found to negatively affect plant reproduction in 'new rare' species that were formerly common. This has been attributed primarily to effects of increased inbreeding but also to pollen limitation. In contrast, little is known about the reproduction of 'old rare' species that are naturally restricted to small and isolated habitats and thus may have developed strategies to cope with long-term isolation and small population size. Here we study the effects of pollen source and quantity on reproduction of the 'old rare' bumblebee-pollinated herb, Astragalus exscapus. In two populations of this species, we tested for pollen autodeposition, inbreeding depression and outbreeding depression. Caged plants were left unpollinated or were pollinated with pollen from the same plant, from the same population or from a distant population (50 km). Additionally, we tested for pollen limitation by pollen supplementation in four populations of different size and density. In the absence of pollinators, plants did not produce seed whereas self-pollinated plants did. This indicates a self-compatible breeding system dependent on insect pollination. Both self-pollination and, in one of the two populations, cross pollination with pollen from plants from the distant population resulted in a lower number of seeds per flower than cross-pollination with pollen from plants from the resident population, indicating inbreeding and outbreeding depression. Pollen addition enhanced fruit set and number of seeds per flower in three of the four populations, indicating pollen limitation. The degree of pollen limitation was lowest in the smallest but densest population. Our results suggest that, similar to 'new rare' plant species, also 'old rare' species may be at risk of inbreeding depression and pollen limitation. PMID- 21972801 TI - Prevalence and classification of toxigenic Staphylococcus aureus isolated from refrigerated ready-to-eat foods (sushi, kimbab and California rolls) in Korea. AB - AIMS: To investigate the presence of toxigenic Staphylococcus aureus in ready-to eat (RTE) Korean foods and determine the distribution of genes related to various types of toxin production. METHODS AND RESULTS: A total of 3293 commercial RTE refrigerated foods (sushi, n = 1882; kimbab, n = 975; California rolls, n = 436) were collected from Korean grocery stores, department stores and convenience stores between January 2006 and June 2007. Of these, 197 (5.98%) RTE samples were contaminated with coagulase-positive Staph. aureus, that is, 61 (6.26%) kimbab, 110 (5.84%) sushi and 26 (5.96%) California rolls. Multiplex PCR determined the presence of 12 toxigenic genes: sea, seb, sec, sed, see, seg, seh, sei, sej, tst 1, eta and etb. Approximately half (49.75%) of the Staph. aureus isolates had toxigenic properties, and most of the toxigenic isolates possessed genes coding for the simultaneous production of two or more types of toxin. The most frequent toxigenic types found in Korean RTE foods were as follows: seg = sei > sea > tst 1 > etb > seh > eta > sec > sej. CONCLUSIONS: This study provided a comprehensive analysis of toxigenic S. aureus isolates from Korean RTE foods and their toxigenicity types. This emphasizes the potential risk of various types of toxigenic Staph. aureus in refrigerated RTE food products, which should be better managed to establish safer food chains in global food markets. SIGNIFICANCE AND IMPACT OF THE STUDY: This result may contribute to an extended database on Staph. aureus food contamination and mitigate the lack of available information on microbiological hazards in Southeast Asian Nations. PMID- 21972802 TI - Salvianolic acid A protects against vascular endothelial dysfunction in high-fat diet fed and streptozotocin-induced diabetic rats. AB - Salvianolic acid A (SalA) is one of the main active ingredients of Salvia miltiorrhizae. The objective of this study was to evaluate the effect of SalA on the diabetic vascular endothelial dysfunction (VED). The rats were given a high fat and high-sucrose diet for 1 month followed by intraperitoneal injection of streptozotocin (30 mg/kg). The diabetic rats were treated with SalA (1 mg/kg, 90% purity) orally for 10 weeks after modeling, and were given a high-fat diet. Contractile and relaxant responses of aorta rings as well as the serum indications were measured. Our results indicated that SalA treatment decreased the level of serum Von Willebrand factor and ameliorated acetylcholine-induced relaxation and KCl-induced contraction in aorta rings of the diabetic rats. SalA treatment also reduced the serum malondialdehyde, the content of aortic advanced glycation end products (AGEs), and the nitric oxide synthase (NOS) activity as well as the expression of endothelial NOS protein in the rat aorta. Exposure of EA.hy926 cells to AGEs decreased the cell viability and changed the cell morphology, whereas SalA had protective effect on AGEs-induced cellular vitality. Our data suggested that SalA could protect against vascular VED in diabetes, which might attribute to its suppressive effect on oxidative stress and AGEs induced endothelial dysfunction. PMID- 21972803 TI - Two new compounds from Comastoma pedunlulatum. AB - Two new compounds, a xanthonoid and a flavonoid C-glycoside, were isolated from the ethyl acetate extract of the dried herb of Comastoma pedunlulatum. The structures of the new compounds were elucidated, respectively, as 1,8-dihydroxy 3,5-dimethoxyxanthone 1-O-[2-(4'-hydroxy-3',5'-dimethoxy-E-cinnamoyl)]-beta-D xylopyranosyl-(1-6)-beta-D-glucopyranoside (1) and 6"-O-acetylisoorientin (2) on the basis of their spectroscopic and physicochemical properties. PMID- 21972804 TI - Three new compounds from soil actinomycete Streptomyces albospinus 15-4-2. AB - Three new compounds, 2-methyl-2,5,6-bornantriol (1), 4,4'-(3-hydroxypropane-1,1 diyl)diphenol (2), and 7-(4-methoxybenzyl)-4,5,6,7-tetrahydro-1,3-oxazepine-5,6 diol (3), were isolated from the fermentation broth of the soil actinomycete Streptomyces albospinus 15-4-2. Their structures were completely elucidated using the combination of 1D, 2D NMR techniques (COSY, HMQC, HMBC, and ROESY), and HR ESI-MS analysis. None of the compounds 1-3 showed any inhibitory effect on Fusarium oxysporum f.sp. cubense race 4. PMID- 21972805 TI - Three new flavonoid glycosides from Urena lobata. AB - Three new flavonoid glycosides, kaempferol-3-O-beta-D-apiofuranosyl(1 -> 2)-beta D-glucopyranosyl-7-O-alpha-L-rhamnopyranoside (1), kaempferol-4'-O-beta-D apiofuranosyl-3-O-beta-D-glucopyranosyl-7-O-alpha-l-rhamnopyranoside (2), and 5,6,7,4'-tetrahydroxy-flavone-6-O-beta-D-arabinopyranosyl-7-O-alpha-L rhamnopyranoside (3), were isolated from the aerial parts of Urena lobata L., along with 10 known compounds (4-13). Their structures were determined based on spectroscopic methods including 1D and 2D NMR spectroscopy as well as HR-ESI-MS. PMID- 21972806 TI - Brachystemols A-C, three new furan derivatives from Brachystemma calycinum. AB - Three new furan derivatives, brachystemols A-C (1-3), and 13 known compounds (4 15) were isolated from the EtOH extract of Brachystemma calycinum. Their structures were identified by means of spectroscopic methods. Compounds 4-13 were isolated from this plant for the first time. PMID- 21972807 TI - Sesquiterpenoids and other constituents from the flower buds of Tussilago farfara. AB - One new norsesquiterpenoid, namely tussfarfarin A (1), and four new artifacts resulting from extraction procedure, namely tussfarfarin B (2), 6-(1-ethoxyethyl) 2,2-dimethylchroman-4-ol (3), 5-ethoxymethyl-1H-pyrrole-2-carbaldehyde (4), and 3beta-hydroxy-7alpha-ethoxy-24beta-ethylcholest-5-ene (5), along with 18 known compounds, were isolated from the flower buds of Tussilago farfara. Their structures were elucidated by extensive spectroscopic analysis. PMID- 21972808 TI - Two new furan derivatives from bee-collected rape pollen. AB - Two new furan derivatives named pollenfurans A (1) and B (2) were isolated from the ethyl acetate extract of bee-collected rape pollen. Their structures were elucidated by spectroscopic analysis. The absolute configurations of the 6,7-diol moiety in both compounds 1 and 2 were confirmed by Snatzke's method, observing the induced circular dichroism after the addition of dimolybdenum tetraacetate in DMSO. PMID- 21972809 TI - Diterpenoids from the freshwater green algae Rhizoclonium hieroglyphicum with antibacterial activity. AB - Three new isopimarane diterpenes 7beta-hydroxy-19alpha-methylmalonyloxy-isopimara 8(14),15-diene (1), 7beta-hydroxy-14-oxo-isopimara-8(9),15-dien-19oic acid (2), and 7beta-hydroxy-14-oxo-19alpha-methylmalonyloxy-isopimara-9(11),15-diene (3) in addition to the known compounds isopimaric acid (4), 7oxo-13-epi-pimara-14,15 dien-18oic acid (5), 7oxo-13-epi-pimara-8,15-dien-18oic acid (6), and 6beta hydroxyisopimaric acid (7) were isolated from the hexane extract of Rhizoclonium hieroglyphicum. The structures of compounds 1-7 were established by 1D and 2D NMR techniques. The isolated diterpenoids were screened for antimicrobial activity against gram-positive and gram-negative bacteria and yeast strains. PMID- 21972810 TI - Glycyrrhetinic acid extracted from Glycyrrhiza uralensis Fisch. induces the expression of Toll-like receptor 4 in Ana-1 murine macrophages. AB - Glycyrrhetinic acid (GA) is an active component of licorice root that has long been used as a herbal medicine for the treatment of peptic ulcer, hepatitis, and pulmonary and skin diseases in Asia and Europe. In this study, we analyzed the effect of GA extracted from Glycyrrhiza uralensis Fisch. on the expression of Toll-like receptors (TLRs) that play key roles in regulating the innate immune response against invading pathogens. Stimulation of Ana-1 murine macrophages with GA induced a significant dose-dependent expression of TLR-4, and its mRNA expression that increased from 3-h post-treatment was approximately fivefold over the level in the mock-treated cells. No endotoxin contamination contributed to the GA-induced TLR-4 expression, because polymyxin B treatment did not alter the upregulated expression of TLR-4 in GA-treated cells. Several molecules, such as myeloid differentiation factor 88, interferon-beta, and interleukin-6, which are involved in the TLR-4 downstream signaling pathway, were upregulated significantly in response to GA stimulation. Our findings demonstrate that GA is able to induce the expression of TLR-4 and activate its downstream signaling pathway. PMID- 21972811 TI - A novel degraded sesquiterpene from the fresh stem of Aquilaria sinensis. AB - A novel degraded sesquiterpene, named aquilarin B (1), together with two known compounds (2 and 3), was isolated from the EtOH extract of the fresh stem of Aquilaria sinensis (Lour.) Gilg. Their structures were elucidated by spectroscopic methods including 1D and 2D NMR (HMQC, (1)H-(1)H COSY, HMBC, and ROESY). The cytotoxic activities of the three compounds against three human tumor cell lines K562, SMMC-7721, and SGC-7901 were evaluated, and compound 3 exhibited obvious cytotoxic activity. PMID- 21972812 TI - A new furanoxanthone from the stem bark of Calophyllum inophyllum. AB - The stem bark extracts of Calophyllum inophyllum furnished one new furanoxanthone, inophinnin (1), in addition to inophyllin A (2), macluraxanthone (3), pyranojacareubin (4), 4-hydroxyxanthone, friedelin, stigmasterol, and betulinic acid. The structures of these compounds were determined by spectroscopic analysis of 1D and 2D NMR spectral data ((1)H, (13)C, DEPT, COSY, HMQC, and HMBC) while EI-MS gave the molecular mass. The new xanthone, inophinnin (1), exhibited some anti-inflammatory activity in nitric oxide assay. PMID- 21972813 TI - A new diterpene from the stems of Manihot esculenta. AB - A new diterpene, named yucalexin P-23 (1), together with three known compounds, yucalexin P-15 (2), protocatechuic acid (3), and catalpinic acid (4), was isolated from the stems of Manihot esculenta. Their structures were determined by means of physicochemical evidence and spectral analysis. Compounds 3 and 4 exhibited antimicrobial activity. PMID- 21972814 TI - A new flavonol glucoside from the aerial parts of Sida glutinosa. AB - Phytochemical investigation on the dried aerial parts of Sida glutinosa has led to the isolation of a new flavonol glucoside, glutinoside (1), along with seven known compounds, 24(28)-dehydromakisterone A (2), 1,2,3,9-tetrahydropyrrolo[2,1 b]-quinazolin-3-amine (3), docosanoic acid, 1-triacontanol, campesterol, stigmasterol, and beta-sitosterol. The structures of these compounds were elucidated by means of extensive spectroscopic techniques as well as GC/MS analysis (for sterols) and comparison with the literature data. All these seven known compounds are reported from this plant for the first time. PMID- 21972815 TI - A new carbazole alkaloid from the leaves of Malayan Murraya koenigii. AB - New carbazole alkaloid, 7-hydroxymurrayazolinine (1), was isolated from the ethanol extract of the leaves of Malayan Murraya koenigii, together with five known carbazole alkaloids, mahanimbine (2), bicyclomahanimbine (3), girinimbine (4), koenimbine (5), and murrayamine-D (6). Their structures were elucidated on the basis of spectroscopic analysis. PMID- 21972816 TI - Phosphatidylinositol 4-phosphate is associated to extracellular lipoproteic fractions and is detected in tomato apoplastic fluids. AB - We have recently detected phosphatidylinositol-4-phosphate (PI4P) in the extracellular medium of tomato cell suspensions. Extracellular PI4P was shown to trigger the activation of defence responses induced by the fungal elicitor xylanase. In this study, by applying a differential centrifugation technique, we found that extracellular PI4P is associated with fractions composed of diverse phospholipids and proteins, which were pelleted from the extracellular medium of tomato cell suspensions grown under basal conditions. Using mass spectrometry, we identified the proteins present in these pelleted fractions. Most of these proteins have previously been characterised as having a role in defence responses. Next, we evaluated whether PI4P could also be detected in an entire plant system. For this, apoplastic fluids of tomato plants grown under basal conditions were analysed using a lipid overlay assay. Interestingly, PI4P could be detected in intercellular fluids obtained from tomato leaflets and xylem sap of tomato plants. By employing electrospray ionisation tandem mass spectrometry (ESI-MS/MS), other phospholipids were also found in intercellular fluids of tomato plants. These had a markedly different profile from the phospholipid pattern identified in entire leaflets. Based on these results, the potential role of extracellular phospholipids in plant intercellular communication is discussed. PMID- 21972817 TI - Common and distinct responses in phytohormone and vitamin E changes during seed burial and dormancy in Xyris bialata and X. peregrina. AB - Temperature and humidity are the main factors influencing seed viability, dormancy and longevity of buried seeds. Unfortunately, very little is known about such processes in species of tropical regions, where temperature does not show major seasonal variations. The extent to which germination capacity, phytohormones and vitamin E levels were altered after burial of seeds of Xyris bialata and X. peregrina (Xyridaceae), two species endemic to rupestrian fields of Brazil, was examined. After 2 months of burial, seed germination capacity remained constant, which is associated with decreases in ABA and IAA content in both species. During this period, zeatin levels also decreased in X. bialata, but not in X. peregrina, the latter showing much lower levels of ABA. During the summer (rainy season), seeds of both species experienced a progressive, but severe, decrease in germination capacity, which reversed at the end of the winter (dry season), thus suggesting secondary dormancy. This dormancy appeared to be caused by drastic decreases in GAs, rather than increases in ABA. Levels of GA(4) decreased to non-detectable values during dormancy in both species. Furthermore, zeatin levels decreased in X. bialata but not in X.peregrina during this period. Both species accumulated gamma-tocopherol as the major vitamin E form, and levels of this antioxidant remained constant or even increased during seed burial; however, X. bialata seeds showed a significant decrease in alpha-tocopherol during seed burial and dormancy. It is concluded that in X. peregrina and X. bialata, (i) burial causes significant changes in the phytohormone levels of seeds; (ii) secondary dormancy is induced in seeds; (iii) a GA(4) decrease, rather than an ABA increase, seems to be involved in the induction of secondary dormancy; and (iv) reductions in alpha-tocopherol in buried seeds are not necessarily indicative of reduced germination capacity. PMID- 21972818 TI - Criteria for prick test using soy sauce. AB - BACKGROUND: We previously reported four cases of soy sauce allergy and noted that new criteria are necessary for the prick test. Soy sauce contains histamine and often causes false-positive reactions in the skin tests. It is important to discuss how to interpret the results of prick tests. MATERIALS AND METHODS: Eight female patients with soy sauce allergy and four female volunteers as controls were given the prick test using 15 sauces and were evaluated according to nine criteria. The volume of histamine in 15 sauces was determined by high-performance liquid chromatography. RESULTS: The conventional criteria resulted in nine different reactions. Some of the control subjects showed false-positive reactions according to the conventional criteria. Histamine was detected in 11 sauces and was not detected in four sauces. The positive ratios of these four sauces were low; there were no positive reactions in controls according to the new criteria. Regardless of patients or controls, the positive ratio evaluated using the conventional criteria was higher than that evaluated using the new criteria in the sauces containing histamine. DISCUSSION: It is difficult to evaluate the results of the prick test using soy sauce with the conventional criteria because the results were different depending on each criterion. Our new criteria are more suitable for evaluating the results of the prick test using soy sauce than the conventional criteria, and they could decrease the number of false-positive reactions. Common diagnostic criteria are needed for prick testing using pseudoallergens. PMID- 21972819 TI - Polar development of preprophase bands and cell plates in the Arabidopsis leaf epidermis. AB - Preprophase bands are belts of cortical microtubules that appear at the end of interphase and predict where cell plates will fuse with parental walls during division. Phragmoplasts are microtubule-rich arrays that orchestrate the growth and guidance of cell plates during cytokinesis. Descriptions of the development of these arrays often assume non-polar formation, with preprophase bands developing more or less simultaneously around the cell circumference. Phragmoplasts are often described as initiating at the cell center and then expanding evenly outwards until fusion with parent cell walls. We analyzed the spatio-temporal development of both arrays because initial observations of array growth in the Arabidopsis leaf epidermis revealed directional variability. Almost all preprophase bands formed in a polar fashion, with initiation and maturation occurring first in the cell cortex near the inside of the leaf, and later in the outer cell cortex. A similar polarity developed in phragmoplasts and cell plates, raising the possibility that polarized division is common in plants. Together, these findings identify additional polar features of the epidermis, and thereby provide a visually accessible system for identifying new proteins and subcellular components involved in the development of cell division and the previously formed division site. PMID- 21972820 TI - Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non-valvular atrial fibrillation from the RE-LY trial. AB - BACKGROUND: Dabigatran etexilate (DE) is an orally absorbed prodrug of dabigatran, a thrombin inhibitor that exerts potent anticoagulant and antithrombotic activity. OBJECTIVES: To characterize the pharmacokinetics of dabigatran in patients with non-valvular atrial fibrillation (AF) from the Randomized Evaluation of Long-term Anticoagulant Therapy (RE-LY) trial and to quantify the effect of selected factors on pharmacokinetic (PK) model parameters. PATIENTS AND METHODS: A total of 27 706 dabigatran plasma concentrations from 9522 patients who received DE 110 or 150 mg twice daily were analyzed with non linear mixed-effects modeling. RESULTS: The pharmacokinetics of dabigatran were best described by a two-compartment disposition model with first-order absorption. The covariates creatinine clearance (CRCL), age, sex, heart failure and the ethnic subgroup 'South Asian' exhibited statistically significant effects on apparent clearance of dabigatran. Body weight and hemoglobin significantly influenced the apparent volume of distribution of the central compartment. Concomitant medication with proton-pump inhibitors, amiodarone and verapamil significantly affected the bioavailability. However, all of the statistically significant factors that were identified, except for renal function status, showed only small to moderate effects (< 26% change in exposure at steady state). On the basis of simulations from the final population PK model, a dose of 75 mg twice daily would result in similar exposure for severely renally impaired patients with CRCL of 15-30 mL min(-1) and patients with normal renal function receiving 150 mg twice daily. CONCLUSIONS: The analysis provides a thorough PK characterization of dabigatran in the AF patient population from RE-LY. None of the covariates investigated, with the exception of renal function, warrants dose adjustment. PMID- 21972821 TI - Narrow mass extraction of time-of-flight data for quantitative analysis of proteins: determination of insulin-like growth factor-1. AB - Methods for quantitative analysis of proteins by mass spectrometry have progressed dramatically. While isotope-dilution approaches using selected reaction monitoring of tryptic peptides (also known as bottom up) have become common, the potential to use narrow mass extraction of high-resolution mass spectra provides a compelling alternative. We investigated the relationships between instrument performance and data processing with the aim of determining whether this approach can lead to robust bioanalytical assays for proteins. Our approach utilized off-line sample preparation combined with online sample extraction coupled to HPLC with the effluent from the analytical column directed to a high-resolution, high-mass accuracy quadrupole time-of-flight (qTOF) mass spectrometer operated in full scan mode. Narrow mass extraction of a single isotope from IGF-1 in the 7+ charge state (m/z 1093.5209) was used to generate extracted ion chromatograms. We found that with appropriate attention to instrument performance and data processing, quantitative protein assays with good sensitivity, high selectivity, and excellent analytical performance can be developed. PMID- 21972822 TI - Magnetic anisotropy in Ni(II)-Y(III) binuclear complexes: on the importance of both the first coordination sphere of the Ni(II) ion and the Y(III) ion belonging to the second coordination sphere. AB - The synthesis of a new Ni(II)-Y(III) binuclear complex with a marked elongation axis in the first coordination sphere of the Ni(II) ion is presented. Its zero field splitting (ZFS) is studied by means of magnetic data and state-of-the-art ab initio calculations. A good agreement between the experimental and theoretical ZFS parameter values is encountered, validating the whole approach. The magnetic anisotropy axes are extracted from the ab initio calculations, showing that the elongation axis around the Ni(II) ion corresponds to the hard axis of magnetization and that the sign of the axial D parameter is imposed by this axis. The Ni-Y axis is found to be an easy axis of magnetization, which is, however, not significant according to the sign of D. The already reported [(H(2)O)Ni(ovan)(2)(MU-NO(3))Y(ovan)(NO(3))].H(2)O (ovan = o-vanillin) complex is then revisited. In this case, the elongation axis in the Ni(II) coordination sphere is less marked and the ZFS is dominated by the effect of the Y(III) ion belonging to the second coordination sphere. As a consequence, the D parameter is negative and the low-temperature behavior is dominated by the Ni-Y easy axis of magnetization. A competition between the first coordination sphere of the Ni(II) ion and the electrostatic effect of the Y(III) ion belonging to the second coordination sphere is then evidenced in both complexes, and the positive and negative D parameters are then linked to the relative importance of both effects in each complex. PMID- 21972823 TI - Tricyclic series of heat shock protein 90 (Hsp90) inhibitors part I: discovery of tricyclic imidazo[4,5-c]pyridines as potent inhibitors of the Hsp90 molecular chaperone. AB - A novel class of heat shock protein 90 (Hsp90) inhibitors was developed after a low throughput screen (LTS) of a focused library containing approximately 21K compounds selected by virtual screening. The initial [1-{3-H-imidazo[4-5 c]pyridin-2-yl}-3,4-dihydro-2H-pyrido[2,1-a]isoindole-6-one] (1) compound showed moderate activity (IC(50) = 7.6 MUM on Hsp82, the yeast homologue of Hsp90). A high-resolution X-ray structure shows that compound 1 binds into an "induced" hydrophobic pocket, 10-15 A away from the ATP/resorcinol binding site. Iterative cycles of structure-based drug design (SBDD) and chemical synthesis led to the design and preparation of analogues with improved affinity. These optimized molecules make productive interactions within the ATP binding site as reported by other Hsp90 inhibitors. This resulted in compound 8, which is a highly potent inhibitor in biochemical and cellular assays (K(d) = 0.35 nM on Hsp90; IC(50) = 30 nM on SKBr3 mammary carcinoma cells) and in an in vivo leukemia model. PMID- 21972824 TI - Chiral allene-containing phosphines in asymmetric catalysis. AB - We demonstrate that allenes, chiral 1,2-dienes, appended with basic functionality can serve as ligands for transition metals. We describe an allene-containing bisphosphine that, when coordinated to Rh(I), promotes the asymmetric addition of arylboronic acids to alpha-keto esters with high enantioselectivity. Solution and solid-state structural analysis reveals that one olefin of the allene can coordinate to transition metals, generating bi- and tridentate ligands. PMID- 21972826 TI - Reversible and irreversible interactions of poly(3-hexylthiophene) with oxygen studied by spin-sensitive methods. AB - Understanding of degradation mechanisms in polymer:fullerene bulk-heterojunctions on the microscopic level aimed at improving their intrinsic stability is crucial for the breakthrough of organic photovoltaics. These materials are vulnerable to exposure to light and/or oxygen, hence they involve electronic excitations. To unambiguously probe the excited states of various multiplicities and their reactions with oxygen, we applied combined magneto-optical methods based on multifrequency (9 and 275 GHz) electron paramagnetic resonance (EPR), photoluminescence (PL), and PL-detected magnetic resonance (PLDMR) to the conjugated polymer poly(3-hexylthiophene) (P3HT) and polymer:fullerene bulk heterojunctions (P3HT:PCBM; PCBM = [6,6]-phenyl-C(61)-butyric acid methyl ester). We identified two distinct photochemical reaction routes, one being fully reversible and related to the formation of polymer:oxygen charge transfer complexes, the other one, irreversible, being related to the formation of singlet oxygen under participation of bound triplet excitons on the polymer chain. With respect to the blends, we discuss the protective effect of the methanofullerenes on the conjugated polymer bypassing the triplet exciton generation. PMID- 21972825 TI - Clinical and biochemical landmarks in systemic autoinflammatory diseases. AB - Systemic autoinflammatory diseases are a group of inherited disorders of the innate immune system characterized by seemingly unprovoked inflammation recurring at variable intervals and involving skin, serosal membranes, joints, and gastrointestinal apparatus, with reactive amyloidosis as a possible severe long term complication. Recent advances in genetics and molecular biology have improved our understanding of the pathogenesis of these diseases, including familial Mediterranean fever, mevalonate kinase deficiency syndrome, tumor necrosis factor receptor-associated periodic syndrome, cryopyrin-associated periodic syndromes, and hereditary pyogenic and granulomatous disorders: the vast majority of these conditions are related to the activation of the interleukin-1 pathway, which results in (or from?) a common unifying pathogenetic mechanism. Their diagnostic identification derives from the combination of clinical data, evaluation of acute phase reactants, clinical efficacy in response to specific drugs, and recognition of specific mutations in the relevant genes, although genetic tests may be unconstructive in some cases. This review will discuss clinical and laboratory clues useful for a diagnostic approach to systemic autoinflammatory diseases. PMID- 21972829 TI - Rural children's attitudes to people with HIV/AIDS in Mali: the causes of stigma. AB - Qualitative research among young people and other community members in rural Mali elicited knowledge and attitudes with regard to HIV/AIDS. Findings indicated that rumours concerning methods of infection are likely to increase the stigmatization of those with the disease. The most frequently stated mode of transmission involved urinating in a place where someone with AIDS had already urinated. Shared clothes, food and water were seen as sources of infection. Both children and teachers recommended that people with AIDS be isolated. Even talking to them would lead to a risk of infection. Discriminatory views were likely to have been reinforced by parents and community elders who possessed the same misinformation. The notion that AIDS results from sexual encounters between young women and dogs belonging to white people in Cote d'Ivoire was also widespread. These discourses may reflect perceived xenophobia and risk to migrants associated with current tensions between the two countries, together with misgivings about Western sexual liberalism. A holistic educational programme is proposed to address not simply HIV/AIDS, but the social context in which infection occurs, with view to combating stigma and discrimination associated with not just HIV but also with migration in this setting. PMID- 21972828 TI - Clinical outcome of acute intoxication due to ingestion of auxin-like herbicides. AB - BACKGROUND: The human toxicity of synthetic auxin analogue herbicides has not been extensively studied. METHODS: Clinical outcome was assessed from medical records of 17 patients who had intentionally ingested auxin pesticides with active ingredients like dicamba, triclopyr, MCPA or mecoprop. The patients were interviewed after discharge to follow outcome (interval 2 to 56 months). RESULT: One patient who had ingested 500 mL of a mecoprop product died of hypotension and respiratory failure 36 hours after hospital admission. The other 16 patients recovered and were discharged by hospital day 28. After discharge, four patients died from causes not related to herbicide intoxication. In the 12 surviving patients, no long-term effects were reported. CONCLUSION: Human toxicity of synthetic auxins appears relatively benign with conservative treatment. However, when the amount ingested is above several hundred milliliters of commercial product, especially in combination of mecoprop with other intoxicants (e.g. alcohol), shock with respiratory failure may develop and lead to death. PMID- 21972830 TI - Gay and bisexual men's experiences of bathhouse culture and sex: 'looking for love in all the wrong places'. AB - The aim of this study was to describe gay and bisexual men's experiences of bathhouses and their perceptions of HIV risk associated with sex in this context. Face-to-face, semi-structured interviews were conducted with a purposive sample of gay and bisexual men-14 HIV-positive and 9 HIV-negative-who reported ever frequenting a bathhouse. The sample was selected from the Polaris HIV Seroconversion Study, a longitudinal open cohort study of documented recent seroconverters and HIV-negative controls in Ontario, Canada. Interview transcripts were analysed using a narrative approach. Four major themes were identified concerning views of gay bathhouse culture and environments; moral conceptions of self and others at a bathhouse; identity management at a bathhouse; and psychosocial functions of gay bathhouses. HIV transmission is a salient component of bathhouse culture; therefore, bathhouses are critical environments for the promotion of safer sex activities among gay and bisexual men. PMID- 21972831 TI - Unwanted pregnancy and sexually transmitted infection among young women in rural Kenya. AB - Early sexual debut and premarital sex are increasingly common features of female adolescence in Kenya-putting girls at the risk of unwanted pregnancy and infection by sexually transmitted infections and HIV/AIDS. Levels of knowledge concerning the protective value of condoms and other contraceptives are high, but unprotected sex is still common. Against this background, this paper examines the strategies used by young women to deal with these risks. Qualitative data were obtained from eight focus group discussions conducted with school attending girls aged between 15 and 19 years in Makueni District of Eastern Kenya. Findings suggest that, despite knowledge of the protective value of condoms and other contraceptives, the use of these methods by girls is hampered by inability to access them, the fear of the side effects of contraceptives, and the desire by girls to remain faithful to their religious calling. Most girls also resort to the use of traditional methods such whose potency and efficacy is unproven. These findings suggest the need to make condoms more easily accessible to girls in rural areas, and also for education in the proper use of 'natural' family planning methods. Young women may also benefit from training in how to be more assertive in sexual negotiations. PMID- 21972832 TI - The intentions of gay men in taking an HIV test. AB - The objective of this study was to determine the contributions of a range of psychosocial, demographic and behavioural variables to gay men's intentions to take an HIV test. A cross-sectional self-report survey was undertaken. Researchers approached patrons of all known gay bars in Glasgow and Edinburgh during May 2000. Questionnaires were completed by 803 men (response rate of 78%). Those with a stronger intention to test had previously tested, and they were younger, with two or more recent unprotected anal sex partners. They perceived their HIV status to be unknown, had less fear of a positive test result, and perceived more benefits of testing. Intention to test in those with two or more recent unprotected anal sex partners was attenuated if accompanied by increased fear of a positive test result. Results are considered in the context of the theories of reasoned action and planned behaviour. Intention to test is far from a unitary phenomenon, and the existence of various sub-groups within the gay population demands a new approach to both research and health promotion. PMID- 21972833 TI - The 'natural' body, God and contraceptive use in the southeastern United States. AB - Data collected among African-American and Caucasian women and men in the southeastern USA indicate that participants' perceptions of nature, God's will and the human body influence reproductive health and decision-making. Attitudes about the health care system, pharmaceutical companies and government programmes for fertility regulation reinforce these views and may negatively affect willingness to use contraceptive methods consistently and correctly. PMID- 21972834 TI - Homophobia and the production of shame: young people and same sex attraction. AB - Research among same-sex attracted young people in Western cultures has described a minority group of adolescents whose sexuality is negated by the significant institutions and people in their lives. Very often, there is a silence in the family and at school about same-sex sexuality and when a young person's homosexuality is suspected or disclosed s/he suffers from denial, discrimination and abuse. Not surprisingly, living in hostile environments leaves such young people at high-risk of drug abuse, depression and suicide. This paper describes some of the ways young people resist being positioned in these negative ways. Using autobiographical stories from 200 same-sex attracted young Australians, we document the discursive field of sexuality in which these young people struggle to construct positive identities. Young people were well aware of dominant discourses which characterized homosexuality as 'evil, diseased and unnatural'. Yet they use different strategies to fault, deflect and discount these negative understandings and to highlight other discourse which positions them positively. PMID- 21972837 TI - Pollen:ovule ratio and its relationship with other floral traits in Papilionoideae (Leguminosae): an evaluation with Argentine species. AB - The pollen:ovule ratio (P/O) has traditionally been used as a rough estimator of plant breeding systems. It has been shown that plant breeding systems are associated with particular floral traits. In this study, we determined the P/O in 21 Leguminosae species from Argentina and explored relationships between P/O and taxonomic position, flower size, floral rewards, pollen presentation and pollination mechanisms. According to the results, 15 out of the 21 species classified were obligate xenogamous, although some of them have been recorded as facultative xenogamous in previous studies. There was a significant effect of taxonomic position (genus), reward type and pollination mechanism on P/O. Species offering only nectar as a floral reward (which were species with a brush mechanism) had a significantly lower P/O than species offering pollen or pollen and nectar. Species with the brush pollination mechanism had the lowest P/O, while species with valvular and pump mechanism had the highest P/O. However, pollen presentation (primary and secondary) and flower size did not have a significant effect on P/O. Our results demonstrate that P/O variability is determined by taxonomic position and pollination mechanism in this plant group. PMID- 21972838 TI - New terms for categorizing the outcome of root canal treatment. PMID- 21972839 TI - Reassessing received wisdom in ALS--pain is common when studied systematically. PMID- 21972840 TI - Pollinator directionality as a response to nectar gradient: promoting outcrossing while avoiding geitonogamy. AB - Plants with multiple flowers could be prone to autonomous self-pollination and insect-mediated geitonogamy, but physiological and ecological features have evolved preventing costs related to autogamy. We studied the rare perennial herb Dictamnus albus as a model plant, with the aim of describing the plant-pollinator system from both plant and pollinator perspectives and analysing features that promote outcrossing in an entomophilous species. The breeding system and reproductive success of D. albus were investigated in experimental and natural conditions, showing that it is potentially self-compatible, but only intra inflorescence insect-mediated selfing is possible. Nectar analysis showed gender biased production towards the female phase, which follows the male phase, and during flowering, full blooming is found in flowers at the bottom of the raceme. Among a wide spectrum of insect visitors, three genera (Bombus, Apis, Megachile) were found to be principal pollinators. A study of insect behaviour showed a tendency towards bottom-to-top flights for the most important pollinators Bombus spp. and Apis mellifera: upward movements on the racemes could be explained by foraging behaviour, from more to less rewarding flowers. In accordance with the 'declining reward hypothesis', bumblebees and honeybees leave the plant when gain of reward is low, after which few flowers are visited, reducing the chance of self-pollen transfer among flowers. Intra-flower self-pollination is prevented in D. albus by protandry and herkogamy, while the nectar-induced sequential pattern of pollinator visits avoids geitonogamy and tends to maximise pollen export, promoting outcrossing. All these features for preventing selfing benefit plant fitness and population genetic structure. PMID- 21972841 TI - Structural dynamics of free proteins in diffraction. AB - Among the macromolecular patterns of biological significance, right-handed alpha helices are perhaps the most abundant structural motifs. Here, guided by experimental findings, we discuss both ultrafast initial steps and longer-time scale structural dynamics of helix-coil transitions induced by a range of temperature jumps in large, isolated macromolecular ensembles of an alpha-helical protein segment thymosin beta(9) (Tbeta(9)), and elucidate the comprehensive picture of (un)folding. In continuation of an earlier theoretical work from this laboratory that utilized a simplistic structure-scrambling algorithm combined with a variety of self-avoidance thresholds to approximately model helix-coil transitions in Tbeta(9), in the present contribution we focus on the actual dynamics of unfolding as obtained from massively distributed ensemble-convergent MD simulations which provide an unprecedented scope of information on the nature of transient macromolecular structures, and with atomic-scale spatiotemporal resolution. In addition to the use of radial distribution functions of ultrafast electron diffraction (UED) simulations in gaining an insight into the elementary steps of conformational interconversions, we also investigate the structural dynamics of the protein via the native (alpha-helical) hydrogen bonding contact metric which is an intuitive coarse graining approach. Importantly, the decay of alpha-helical motifs and the (globular) conformational annealing in Tbeta(9) occur consecutively or competitively, depending on the magnitude of temperature jump. PMID- 21972842 TI - Multiplex PCR assay for species identification of bovine mastitis pathogens. AB - AIM: To develop and evaluate a multiplex PCR (mPCR) assay for simultaneous detection of 10 bacterial species causing bovine mastitis namely, Staphylococcus aureus, Staphylococcus chromogenes, Staphylococcus epidermidis, Staphylococcus sciuri, Staphylococcus haemolyticus, Staphylococcus simulans, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus uberis and Escherichia coli in milk. METHODS AND RESULTS: A two-tube mPCR assay was developed. The accuracy of the mPCR was evaluated using 56 standard reference strains and 705 strains comprising of E. coli (n = 99), staphylococci (n = 522) and streptococci (n = 84). The threshold of detection of the mPCR assay was 10 fg of genomic DNA and <10(3) CFU ml(-1). A comparative evaluation of mPCR with culture method using 115 milk samples from subclinical mastitis showed mPCR to be more efficacious. Subsequently, the mPCR showed successful detection of target bacteria, when applied directly for the assessment of 36 bulk milk samples. CONCLUSION: The developed mPCR assay was found to be simple, rapid, reliable and specific in species identification of 10 bacteria at a time. SIGNIFICANCE AND IMPACT OF THE STUDY: The assay will be useful for the detection of mastitis, testing bacteriological safety of milk and for species level differentiation. The assay will be of value in the dairy sector for diagnosis and research. The early and accurate identification of pathogens will enable timely interventions for the treatment and control of bovine mastitis. PMID- 21972843 TI - Addressing social barriers and closing the gender knowledge gap: exposure to road shows is associated with more knowledge and more positive beliefs, attitudes and social norms regarding exclusive breastfeeding in rural Zimbabwe. AB - Exclusive breastfeeding (EBF) is rarely practiced despite its significant child survival benefits. A key constraint to increasing EBF rates in Zimbabwe and most of the developing world is that key decision makers (fathers/partners and other family members) are often poorly informed about EBF and do not attend antenatal clinics where health information is routinely provided. Informed by formative research, a district-wide campaign was conducted in rural Zimbabwe to encourage EBF and expressing and heat treating (EHT) breast milk as a means to maintain EBF. The campaign combined traditional strategies of education, counselling and outreach through health service delivery with a novel road show 'edutainment' intervention to reach men and other community members. A post campaign evaluation measured the association of road show exposure with 20 knowledge items and summative scores of social norms, beliefs and attitudes obtained through exploratory factor analysis. In adjusted models, road show exposure was associated with correct EBF knowledge (beta=1.0, 0.001), EHT knowledge (beta=1.3, P<0.001) and greater perceived benefits of condom use during pregnancy and breastfeeding (beta=0.5, P<0.001), and more positive EBF social norms (beta=0.6, P<0.001), EBF beliefs and attitudes (beta=1.0, P<0.001) and attitudes towards condom use during breastfeeding (beta=0.6, P<0.001). Road show exposure was more strongly associated with EBF knowledge among men (P-value for gender*exposure group interaction=0.03), suggesting that it also closed the knowledge gap between men and women. Longitudinal studies will determine whether road shows were associated with changes in EBF practices. PMID- 21972844 TI - Flow-through microvial facilitating interface of capillary isoelectric focusing and electrospray ionization mass spectrometry. AB - A capillary electrophoresis mass spectrometry (CE-MS) interface utilizing a flow through microvial is used to ensure the electric continuity and supply the catholyte and mobilizer solutions during the capillary isoelectric focusing (cIEF) and mobilization process. The flow-through microvial provides a stable chemical environment and helps to improve the ionization efficiency without significantly diluting the analyte. The CE-MS interface facilitates the transfer of the mobilized cIEF effluent to the site of electrospray ionization, and the gaseous ions can be detected directly by a mass spectrometer. It also allows for complete focusing and mobilization processes to be performed automatically in programmed sequences with commercial CE systems. Two different strategies, using either a part of the capillary or the flow-through microvial of the CE-MS interface as the catholyte reservoir for bare fused silica capillaries or neutral coated capillaries, respectively, were developed for automated cIEF-electrospray ionization (ESI)-MS. Reasonable separation efficiency was achieved using proper concentration of carrier ampholytes and suitable strategies of electroosmotic/electrophoretic mobilization. PMID- 21972845 TI - Vacuoles release sucrose via tonoplast-localised SUC4-type transporters. AB - Arabidopsis thaliana has seven genes for functionally active sucrose transporters. Together with sucrose transporters from other dicot and monocot plants, these proteins form four separate phylogenetic groups. Group-IV includes the Arabidopsis protein SUC4 (synonym SUT4) and related proteins from monocots and dicots. These Group-IV sucrose transporters were reported to be either tonoplast- or plasma membrane-localised, and in heterologous expression systems were shown to act as sucrose/H(+) symporters. Here, we present comparative analyses of the subcellular localisation of the Arabidopsis SUC4 protein and of several other Group-IV sucrose transporters, studies on tissue specificity of the Arabidopsis SUC4 promoter, phenotypic characterisations of Atsuc4.1 mutants and AtSUC4 overexpressing (AtSUC4-OX) plants, and functional comparisons of Atsuc4.1 and AtSUC4-OX vacuoles. Our data show that SUC4-type sucrose transporters from different plant families (Brassicaceae, Cucurbitaceae and Solanaceae) localise exclusively to the tonoplast, demonstrating that vacuolar sucrose transport is a common theme of all SUC4-type proteins. AtSUC4 expression is confined to the stele of Arabidopsis roots, developing anthers and meristematic tissues in all aerial parts. Analyses of the carbohydrate content of WT and mutant seedlings revealed reduced sucrose content in AtSUC4-OX seedlings. This is in line with patch-clamp analyses of AtSUC4-OX vacuoles that characterise AtSUC4 as a sucrose/H(+) symporter directly in the tonoplast membrane. PMID- 21972846 TI - The clinical and radiographic outcome of immediately loaded mini implants supporting a mandibular overdenture. A 3-year prospective study. AB - This article aimed to examine the clinical and radiographic outcome of mini dental implants (MDIs) supporting a mandibular overdenture. Twenty-eight patients (16 men and 12 women) complaining from insufficient retention of their mandibular denture received a total of 112 MDIs (four per patient) in the interforaminal area of the mandible using the non-submerged flapless surgical approach. Implants were immediately loaded with mandibular overdentures after implant insertion. Each implant was evaluated at the time of initial prosthetic loading, 6, 12, 24 and 36 months thereafter. Clinical evaluation was performed using plaque index (PI), gingival index (GI), probing depth (PD) and periotest values (PTVs). Radiographic evaluation was performed in terms of vertical (VBLO) and horizontal (HBLO) alveolar bone loss. Cumulative success and survival rates were calculated using life table analysis. Plaque index, GI, PD, VBLO and HBLO increased significantly in the first year after overdenture insertion, and no significant difference between subsequent observations was noted. Periotest values demonstrated no significant difference between observation times. The cumulative survival and success rates of MDIs were 96.4% and 92.9%, respectively. Within the limitations of this study, clinical and radiographic peri-implant tissue responses of immediately loaded MDIs supporting a mandibular overdenture were favourable after 3 years. However, randomised, controlled clinical trials are needed to compare these responses to that of conventional-diameter implants. PMID- 21972847 TI - Effect of chlorhexidine on denture biofilm accumulation. AB - PURPOSE: Adequate denture hygiene can prevent and treat infection in edentulous patients, who are frequently elderly and have difficulty brushing their teeth. This study evaluated the efficacy of complete denture biofilm removal using a chlorhexidine solution in two concentrations: 0.12% and 2.0%. MATERIALS AND METHODS: Sixty complete denture wearers participated in a trial for 21 days after receiving brushing instructions. They were distributed into three groups, according to the tested solution and regimen (n = 20): (G1) Control (daily overnight soaking in water); (G2) daily immersion at home in 0.12% chlorhexidine for 20 minutes after dinner; and (G3) a single immersion in 2.0% chlorhexidine for 5 minutes at the end of the experimental period, performed by a professional. Biofilm coverage area (%) was quantified on the internal surface of maxillary dentures at baseline and after 21 days. Afterward, the differences between initial and posttreatment results were compared by means of the Kruskal-Wallis test (alpha= 0.05). RESULTS: Median values for biofilm coverage area after treatment were: (G1) 36.0%; (G2) 5.3%; and (G3) 1.4%. Differences were significant (KW = 35.25; p < 0.001), although G2 and G3 presented similar efficacy in terms of biofilm removal. CONCLUSIONS: Both chlorhexidine-based treatments had a similar ability to remove denture biofilm. Immersion in 0.12% or 2.0% chlorhexidine solutions can be used as an auxiliary method for cleaning complete dentures. PMID- 21972848 TI - Factor VIII deficiency does not protect against atherosclerosis. AB - BACKGROUND: Hemophilia A patients have a lower cardiovascular mortality rate than the general population. Whether this protection is caused by hypocoagulability or decreased atherogenesis is unclear. OBJECTIVES: To evaluate atherosclerosis and endothelial function in hemophilia A patients with and without obesity as well as in matched, unaffected controls. METHODS: Fifty-one obese (body mass index [BMI] >= 30 kg m(-2)) and 47 non-obese (BMI <= 25 kg m(-2)) hemophilia A patients, and 42 obese and 50 matched non-obese male controls were included. Carotid and femoral intima-media thickness [IMT] and brachial flow-mediated dilatation (FMD) were measured as markers of atherogenesis and endothelial function. RESULTS: The overall population age was 50 +/- 13 years. Carotid IMT was increased in obese subjects (0.77 +/- 0.22 mm) as compared with non-obese subjects (0.69 +/- 0.16 mm) [mean difference 0.07 mm (95% confidence interval [CI] 0.02-0.13, P = 0.008)]. No differences in mean carotid and femoral IMT between obese hemophilic patients and obese controls were found (mean difference of 0.02 mm [95% CI ) 0.07 0.11, P = 0.67], and mean difference of 0.06 mm [95% CI ) 0.13-0.25, P = 0.55], respectively). Thirty-five per cent of the obese hemophilic patients and 29% of the obese controls had an atherosclerotic plaque (P = 0.49), irrespective of the severity of hemophilia. Brachial FMD was comparable between obese hemophilic patients and obese controls (4.84% +/- 3.24% and 5.32% +/- 2.37%, P = 0.45). CONCLUSION: Hemophilia A patients with obesity develop atherosclerosis to a similar extent as the general male population. Detection and treatment of cardiovascular risk factors in hemophilic patients is equally necessary. PMID- 21972850 TI - Tris(2-(1H-pyrazol-1-yl)pyridine)cobalt(III) as p-type dopant for organic semiconductors and its application in highly efficient solid-state dye-sensitized solar cells. AB - Chemical doping is an important strategy to alter the charge-transport properties of both molecular and polymeric organic semiconductors that find widespread application in organic electronic devices. We report on the use of a new class of Co(III) complexes as p-type dopants for triarylamine-based hole conductors such as spiro-MeOTAD and their application in solid-state dye-sensitized solar cells (ssDSCs). We show that the proposed compounds fulfill the requirements for this application and that the discussed strategy is promising for tuning the conductivity of spiro-MeOTAD in ssDSCs, without having to rely on the commonly employed photo-doping. By using a recently developed high molar extinction coefficient organic D-pi-A sensitizer and p-doped spiro-MeOTAD as hole conductor, we achieved a record power conversion efficiency of 7.2%, measured under standard solar conditions (AM1.5G, 100 mW cm(-2)). We expect these promising new dopants to find widespread applications in organic electronics in general and photovoltaics in particular. PMID- 21972849 TI - The impact of continuity editing in narrative film on event segmentation. AB - Filmmakers use continuity editing to engender a sense of situational continuity or discontinuity at editing boundaries. The goal of this study was to assess the impact of continuity editing on how people perceive the structure of events in a narrative film and to identify brain networks that are associated with the processing of different types of continuity editing boundaries. Participants viewed a commercially produced film and segmented it into meaningful events, while brain activity was recorded with functional magnetic resonance imaging (MRI). We identified three degrees of continuity that can occur at editing locations: edits that are continuous in space, time, and action; edits that are discontinuous in space or time but continuous in action; and edits that are discontinuous in action as well as space or time. Discontinuities in action had the biggest impact on behavioral event segmentation, and discontinuities in space and time had minor effects. Edits were associated with large transient increases in early visual areas. Spatial-temporal changes and action changes produced strikingly different patterns of transient change, and they provided evidence that specialized mechanisms in higher order perceptual processing regions are engaged to maintain continuity of action in the face of spatiotemporal discontinuities. These results suggest that commercial film editing is shaped to support the comprehension of meaningful events that bridge breaks in low-level visual continuity, and even breaks in continuity of spatial and temporal location. PMID- 21972851 TI - An evaluation of graduated driver licensing effects on fatal crash involvements of young drivers in the United States. AB - OBJECTIVE: Graduated driver licensing (GDL) systems are designed to reduce the high crash risk of young novice drivers. Almost all states in the United States have some form of a 3-phase GDL system with various restrictions in the intermediate phase. Studies of the effects of GDL in various states show significant reductions in fatal crash involvements of 16- and 17-year-old drivers; however, only a few national studies of GDL effects have been published. The objective of this national panel study was to evaluate the effect of GDL laws on the fatal crash involvements of novice drivers while controlling for possible confounding factors not accounted for in prior studies. METHODS: The Fatality Analysis Reporting System (FARS) was used to examine 16- and 17-year-old driver involvement in fatal crashes (where GDL laws are applied) relative to 2 young driver age groups (19-20, 21-25) where GDL would not be expected to have an effect. Dates when various GDL laws were adopted in the states between 1990 and 2007 were coded from a variety of sources. Covariates in the longitudinal panel regression analyses conducted included 4 laws that could have an effect on 16- and 17-year-old drivers: primary enforcement seat belt laws, zero-tolerance (ZT) alcohol laws for drivers younger than age 21, lowering the blood alcohol concentration limit for driving to 0.08, and so-called use and lose laws where drivers aged 20 and younger lose their licenses for underage drinking violations. RESULTS: The adoption of a GDL law of average strength was associated with a significant decrease in fatal crash involvements of 16- and 17-year-old drivers relative to fatal crash involvements of one of the 2 comparison groups. GDL laws rated as "good" showed stronger relationships to fatal crash reductions, and laws rated as "less than good" showed no reductions in crash involvements relative to the older driver comparison groups. CONCLUSIONS: States that adopt a basic GDL law can expect a decrease of 8 to 14 percent in the proportion of 16- and 17-year old drivers involved in fatal crashes (relative to 21- to 25-year-old drivers), depending upon their other existing laws that affect novice drivers, such as those used in these analyses. This finding is consistent with recent national studies that used different outcome measures and covariates. The results of this study provide additional support for states to adopt, maintain, and upgrade GDL systems to reduce youthful traffic crash fatalities. PMID- 21972853 TI - An analysis of U.S. road fatalities per population: changes by age from 1958 to 2008. AB - OBJECTIVE: This article presents a time-series analysis of changes in road safety in the United States from a public-health point of view. METHOD: A 50-year period was examined, from 1958 to 2008. The emphasis was on the changes by decades in fatalities per population across different age groups. RESULTS: First, from 1958 to 2008, the overall fatality rate per population decreased by 40 percent. Second, the decrease in the rate was age dependent (with the largest decreases for the youngest and the oldest, and the smallest decreases for the middle-aged). Third, the overall fatality rate increased from 1958 to 1968, but it decreased for each of the 4 following decades. Fourth, the changes in the rate for each decade were age dependent. Fifth, the patterns of these age-dependent changes varied across the decades. CONCLUSIONS: Examples of interventions that are likely to have age-dependent effects consistent with the obtained differential age changes in the fatality rate are discussed. However, other interventions are also likely to have relevant age-dependent effects on the fatality rate. PMID- 21972852 TI - Effect of a postviolation driver improvement class on traffic convictions and crashes. AB - OBJECTIVE: To investigate the effect of a driver improvement class on postclass moving traffic violations and crashes among drivers charged with speeding. METHODS: A total of 5079 drivers who completed an 8-hour class were compared to a control group of 25,275 drivers from the same locale who had been convicted of speeding during the same time period but had not taken the class. Counts of convictions and crashes were available for all drivers for 2 years prior to the class and between 1 and 3 years after the class or key speeding conviction. Zero inflated negative binomial models were used to measure the expected number of convictions among those who took the class compared with subjects who did not take it. RESULTS: Individuals with a moving violation conviction had 2.5 times the odds of having previous convictions for moving violations and almost 1.5 times the odds of having been involved in a crash. Drivers who took the class had convictions similar to the control group after the class (Incidence Rate Ratio [IRR]: 1.03, 95% confidence interval [CI]: 0.95-1.12) but were less likely to be involved in subsequent crashes (IRR: 0.83, 95% CI: 0.77-0.91). CONCLUSIONS: The results suggest that among drivers overall, exposure to driver improvement classes as a means to change drivers' behaviors is not significantly associated with fewer convictions for moving violations but may be effective in reducing crashes. PMID- 21972854 TI - Prevalence and correlates of street racing among Ontario high school students. AB - OBJECTIVES: This study examined the prevalence and correlates of street racing among adolescents derived from the 2009 Ontario Student Drug Use and Health Survey (OSDUHS), an epidemiological survey of students in Ontario, Canada. METHODS: The key response variable, self-reported street racing in past year, was examined in relation to grade level, rural/urban, school marks, cannabis use, drinking and driving, cannabis use and driving, and property, physical, drugs, and weapons delinquencies. All survey estimates were weighted, and variance and statistical tests were corrected for the complex sampling design. RESULTS: Of the 3053 9th- to 12th-graders (66% response rate), 5.6 percent of high-schoolers (an estimated 42,000 in the province) and (20.4% of grade 11 and 12 students with an advanced-level or full license) reported driving a car, truck, or sport utility vehicle (SUV) in a street race in the 12 months before the survey. Logistic regression analysis of the advanced-level or fully licensed students in grades 11 and 12 found that males compared to females and students in grade 11 compared to students in grade 12 had significantly higher adjusted odds of street racing. Supportive of problem behavior theory, students who reported property and drug delinquencies compared to students not engaging in these delinquencies also had significantly higher adjusted odds of street racing. CONCLUSIONS: This first population-based study in North America suggested that the prevalence of street racing at 1 in 5 of advanced or fully licensed high-schoolers in grades 11 and 12 poses significant public health concerns, especially related to the potential for unintentional injury. PMID- 21972855 TI - An evaluation of the roadwise review: a mixed methods approach. AB - OBJECTIVE: The objective of this mixed methods study was to perform an evaluation of the Roadwise Review CD-ROM (RWR), a self-screening tool for older drivers. METHODS: Ninety-six older drivers (67 to 91) used the RWR with a research assistant at two different sites, and then completed written surveys (closed and open-ended questions) immediately after the session as well as two weeks later. In addition, RWR test results by these 96 older drivers were compared to the results of the original sample that was used to establish normative data for the RWR. RESULTS: When test scores were evaluated, almost all participants (96%) were found to have at least one impairment. The rates of impairment varied dramatically between tests from 3 percent (visual acuity) to 75 percent (visual search). Several average test scores were found to be different from the original samples upon which the normative data were derived. Several factors were found that influenced these older drivers' scores on the various components of the RWR, although the explanatory power was very low. Participants reported that the RWR was useful, they made changes to their driving, and talked to their family and friends about driving. Participants also provided many good suggestions for improvements of this tool. CONCLUSION: The RWR offers promise for older drivers to self-screen their ability to drive as well as provide education on safe driving, however modifications are recommended for this tool. PMID- 21972856 TI - Older drivers, crashes and injuries. AB - OBJECTIVE: This article aimed to identify the main features of older driver casualty crashes, including detailed descriptions of injury outcomes. METHODS: Data were obtained from the Transport Accident Commission insurance claims database for 2 groups of drivers: aged 41 to 55 years (middle-aged drivers) and aged 65 years and older (older drivers). RESULTS: In terms of crash circumstances, the majority of crashes involved a collision with another vehicle (70.0% of middle-aged drivers and 68.7% of older drivers). The 2 main maneuvers at the time of crash were driving straight ahead (44.6% of middle-aged drivers and 42.8% of older drivers) and turning right (equivalent of left turn in North America; 15.2% of middle-aged drivers and 17.6% of older drivers). In terms of injury outcomes, older drivers sustained a significantly higher proportion of injuries to the thorax (30.9% compared to 18.5% of middle-aged drivers). Conversely, a significantly higher proportion of middle-aged drivers sustained some form of injury to the neck (30.6% compared to 12.1% of older drivers). CONCLUSION: These findings highlight the situations that are particularly risky for older drivers and provide important insights for developing solutions to reduce older driver crash and injury risk. PMID- 21972857 TI - Driving habits and risk exposure in older drivers: lessons learned from the implementation of a self-regulation curriculum. AB - OBJECTIVE: This article describes the development and pilot testing of Seniors on the MOVE (Mature Operators Vehicular Education), a safe driving education program for older adults. The study aims are to describe driving experiences and habits of a community sample of older drivers and to determine whether the program reduces their driving risk exposures. METHODS: A 2-group randomized design was used. Fifty-eight participants with an average age of 70 were randomly assigned to the MOVE program or a no treatment control group. MOVE is a 4-session program designed to help older drivers better understand and utilize self-regulation skills for safer driving. Baseline and 4-week follow-up questionnaires were completed by both groups, after which the control group received the MOVE program. RESULTS: In the total sample, 14 percent reported having ever been in a traffic crash where someone was injured, and 10 percent reported having received a traffic citation in the past 6 months. Almost one half of the sample (47%) reported thinking about reducing the amount of driving done at night. Nearly one third were thinking about reducing the amount of driving done in unfamiliar places (32%) and the number of miles driven each week (30%). Participants reported most frequently driving between 2 to 10 miles from home, on local roadways, and between 9:00 am and 4:00 pm. Based on responses to items that measured such driving habits, a risk exposure score was created by combining driving exposure variables. Participants were categorized into lower and higher driving risk exposure groups at baseline and follow-up. There were no statistical differences in changes in higher or lower risk driving exposure variables when comparing the 2 groups. CONCLUSIONS: Although the impact of this program on reported driving behaviors yielded null results, descriptions of older drivers' habits and plans are informative. Because many participants were thinking about making changes to their driving habits, and many already had, the need for more effective self-regulation driving safety programs to help with this process is clear. PMID- 21972858 TI - Attempts at the practical on-road driving test and the hazard perception test and the risk of traffic crashes in young drivers. AB - OBJECTIVE: This study separately examined the impact of the outcomes of a practical on-road driving test and a hazard perception test on the likelihood of traffic crashes among a cohort of newly licensed young drivers in New South Wales (NSW), Australia. METHODS: The DRIVE study is a prospective cohort study of drivers aged 17 to 24 years holding their first-year provisional driver license in NSW. Information obtained from 20,822 participants in a detailed baseline questionnaire was linked to information on the number of attempts at a mandatory practical on-road driving test and hazard perception test as well as police reported traffic crashes. RESULTS: After controlling for a number of sociodemographic and behavioral factors as well as factors related to driver learning experiences, multivariate analysis showed that those who failed the practical on-road test at least 4 times had an increased risk of involvement in a traffic crash compared to those who passed the test at first attempt (relative risk [RR]: 1.79, 95% confidence interval [CI]: 1.20-2.65). The crash risk among those who failed the practical on-road test at least 4 times was particularly high in females (RR: 2.10, 95% CI: 1.20-3.68). Similarly, those who failed the hazard perception test at least twice had an increased risk of involvement in a traffic crash (RR: 1.83, 95% CI: 1.27-2.63) compared to those who passed the test on the first attempt. The crash risk of those who failed the hazard perception test at least twice was particularly high in males (RR: 2.5, 95% CI: 1.5-4.1) and among those from rural and remote areas (RR: 5.53, 95% CI: 1.63-18.71). CONCLUSIONS: The findings have implications on licensing practices and suggest the need for adequate strategies to assist young drivers with multiple failures in the driving and hazard perception tests. PMID- 21972859 TI - Visual field defects may not affect safe driving. AB - OBJECTIVE: In Quebec a driver whose acquired visual field defect renders them ineligible for a driver's permit renewal may request an exemption from the visual field standard by demonstrating safe driving despite the defect. For safety reasons it was decided to attempt to identify predictors of failure on the road test in order to avoid placing driving evaluators in potentially dangerous situations when evaluating drivers with visual field defects. METHODS: During a 4 month period in 2009 all requests for exemptions from the visual field standard were collected and analyzed. All available medical and visual field data were collated for 103 individuals, of whom 91 successfully completed the evaluation process and obtained a waiver. RESULTS: The collated data included age, sex, type of visual field defect, visual field characteristics, and concomitant medical problems. No single factor, or combination of factors, could predict failure of the road test. All 5 failures of the road test had cognitive problems but 6 of the successful drivers also had known cognitive problems. Thus, cognitive problems influence the risk of failure but do not predict certain failure. CONCLUSION: Most of the applicants for an exemption were able to complete the evaluation process successfully, thereby demonstrating safe driving despite their handicap. Consequently, jurisdictions that have visual field standards for their driving permit should implement procedures to evaluate drivers with visual field defects that render them unable to meet the standard but who wish to continue driving. PMID- 21972860 TI - In-depth evaluation of real-world car collisions: fatal and severe injuries in children are predominantly caused by restraint errors and unstrapped cargo. AB - OBJECTIVE: Major improvements have taken place in the development of child restraint systems and in-car safety in general, but motor vehicle accidents remain the leading cause of death and disability in children. An interdisciplinary study was therefore performed to investigate the injury mechanisms in car collisions involving children. METHODS: Motor vehicle collisions (MVCs) resulting in death or serious injuries to the drivers or their passengers in the southeastern part of Norway in the period 2007-2009 were included in the study if children less than 16 years of age were passengers. An investigation team examined the crash scene within 24 h of the accident. The internal and external environment of the vehicle was investigated, with particular focus on safety equipment and registration of child occupant contact points. Information was collected from witnesses, crash victims, the police, road authority reports, and medical records. Clinical or postmortem examinations were performed on the child occupants. RESULTS: Fifteen high-impact car crashes involving 27 child occupants were investigated: 7 children died (median [range] age 8 (0-15) years), 8 were severely injured (8 [5-13] years), and 12 sustained minor or no injuries (3.5 [0-14] years). Fourteen out of 15 fatalities or severe injuries (MAIS >=3) were found to be due to various safety errors: harness straps or seat belts incorrectly routed (5/15) or poorly adjusted (4/15), unstrapped luggage (4/15), or technical errors (1/15). All 7 of the fatally injured children died at the crash scene, and 6 died due to head/upper neck trauma. No safety errors were found among the 12 children with either minor or no injuries. No association was found between the instantaneous change in velocity (DeltaV) and the injury severity. CONCLUSION: The risk of child passengers being severely or fatally injured in MVCs is significantly higher when they are incorrectly restrained or exposed to unsecured heavy luggage. Appropriate crash investigations may provide important information regarding the injury mechanisms, which will be necessary for the implementation of preventive measures to reduce future fatalities. PMID- 21972861 TI - IIHS side crash test ratings and occupant death risk in real-world crashes. AB - OBJECTIVE: To evaluate how well the Insurance Institute for Highway Safety (IIHS) side crash test ratings predict real-world occupant death risk in side-impact crashes. METHODS: The IIHS has been evaluating passenger vehicle side crashworthiness since 2003. In the IIHS side crash test, a vehicle is impacted perpendicularly on the driver's side by a moving deformable barrier simulating a typical sport utility vehicle (SUV) or pickup. Injury ratings are computed for the head/neck, torso, and pelvis/leg, and vehicles are rated based on their ability to protect occupants' heads and resist occupant compartment intrusion. Component ratings are combined into an overall rating of good, acceptable, marginal, or poor. A driver-only rating was recalculated by omitting rear passenger dummy data. Data were extracted from the Fatality Analysis Reporting System (FARS) and National Automotive Sampling System/General Estimates System (NASS/GES) for the years 2000-2009. Analyses were restricted to vehicles with driver side air bags with head and torso protection as standard features. The risk of driver death was computed as the number of drivers killed (FARS) divided by the number involved (NASS/GES) in left-side impacts and was modeled using logistic regression to control for the effects of driver age and gender and vehicle type and curb weight. Death rates per million registered vehicle years were computed for all outboard occupants and compared by overall rating. RESULTS: Based on the driver-only rating, drivers of vehicles rated good were 70 percent less likely to die when involved in left-side crashes than drivers of vehicles rated poor, after controlling for driver and vehicle factors. Compared with vehicles rated poor, driver death risk was 64 percent lower for vehicles rated acceptable and 49 percent lower for vehicles rated marginal. All 3 results were statistically significant. Among components, vehicle structure rating exhibited the strongest relationship with driver death risk. The vehicle registration-based results for drivers were similar, suggesting that the benefit was not due to differences in crash risk. The same pattern of results held for outboard occupants in nearside crashes per million registered vehicle years and, with the exception of marginally rated vehicles, also held for other crash types. CONCLUSIONS: Results show that IIHS side crash test ratings encourage designs that improve crash protection in meaningful ways beyond encouraging head protection side air bags, particularly by promoting vehicle structures that limit occupant compartment intrusion. Results further highlight the need for a strong occupant compartment and its influence in all types of crashes. PMID- 21972862 TI - Modeling occupants in far-side impacts. AB - Far-side impacts are not part of any regulated NCAP, FMVSS, or similar test regime despite accounting for 43 percent of the seriously injured persons and 30 percent of the harm in U.S. side impact crashes. Furthermore, injuries to the head and thorax account for over half of the serious injuries sustained by occupants in far-side crashes. Despite this, there is no regulated or well accepted anthropomorphic test device (ATD) or computer model available to investigate far-side impacts. As such, this presents an opportunity to assess a computer model that can be used to measure the effect of varying restraint parameters on occupant biomechanics in far-side impacts. OBJECTIVE: This study sets out to demonstrate the modified TASS human facet model's (MOTHMO) capabilities in modeling whole-body response in far-side impacts. METHOD: MOTHMO's dynamic response was compared to that of postmortem human subjects (PMHS), WorldSID, and Thor-NT in a series of far-side sled tests. The advantages, disadvantages, and differences of using MOTHMO compared to ATDs were highlighted and described in terms of model design and instrumentation. Potential applications and improvements for MOTHMO were also recommended. RESULTS: The results showed that MOTHMO is capable of replicating the seat belt-to-shoulder complex interaction, pelvis impacts, head displacement, neck and shoulder belt loading from inboard mounted belts, and impacts from multiple directions. Overall, the model performed better than Thor-NT and at least as well as WorldSID when compared to PMHS results. Though WorldSID and Thor-NT ATDs were capable of reproducing many of these impact loads, measuring the seat belt-to-shoulder complex interaction and thoracic deflection at multiple sites and directions was less accurately handled. CONCLUSION: This study demonstrated that MOTHMO is capable of modeling whole-body response in far-side impacts. Furthermore, MOTHMO can be used as a virtual design tool to explore the effect of varying restraint parameters on occupant kinematics in far-side crash configurations. PMID- 21972863 TI - Attentional networks functioning, age, and attentional lapses while driving. AB - OBJECTIVE: Based on Posner's (1994) model of attentional functions, the relationship between age and personal proneness to attention-related errors while driving and the functioning of the 3 attentional networks were explored by means of attentional behavioral measures and self-report data. METHODS: A sample of 55 drivers was drawn from the general population of Mar del Plata, Buenos Aires, Argentina. The Attention Network Test for Interactions (ANTI) (Callejas et al. 2004) task was used to obtain behavioral measures of the attentional networks, and we used the Attention-Related Driving Error Scale (ARDES) (Ledesma et al. 2010) questionnaire to obtain a self-report measure of attention-related driving errors. RESULTS: Drivers reporting the greatest propensity to experience attention-related errors showed an overall slowdown in performance, less endogenous preparation for high = priority warning signs, and a better response to conflict in the presence of valid cues than drivers less prone to attention related errors while driving. Older participants showed a slowdown in performance, less endogenous preparation for high-priority warning signs, and worse cognitive control when solving conflict in comparison with younger drivers. CONCLUSIONS: We suggest that each group variable, attention-related error proneness and age, shows a particular combination of attentional network functioning that implies different ways of being distracted, which have different practical implications for safe driving. It can be inferred that drivers who are more prone to commit attentional errors while driving run less risk in situations in which they can deal with response conflict in the presence of valid cues because of the particular way in which their attentional networks are combined when a valid cue is present, could serve to compensate, with a better response conflict, their general slowdown and less endogenous preparedness for high priority signs. It can be inferred that older drivers might show a reduction of the general state of alertness to signs that indicate the presence of a dangerous driving situation and in solving conflict in traffic circumstances. PMID- 21972864 TI - Investigation into the effect of an intersection crash warning system on driving performance in a simulator. AB - OBJECTIVE: The objective of this research was to examine the effects on driving performance of a prototype intersection collision warning system (ICWS) that is based on the dedicated short-range communication (DSRC) technology concept. METHODS: An experimental study with 32 participants using a driving simulator was conducted to examine the effects of ICWS on the driving performance of different drivers sorted by gender (male, female) and experience (experienced, novice) compared across 3 warning conditions: no warning, audio warning, and visual warning. Each participant completed 3 test, drives with each drive comprising 3 events. Each event contained a combination of scenario type (cross-traffic from left/right scenario, right turn against scenario) and warning condition. RESULTS: The results showed that an ICWS, in general, could reduce the number of intersection crashes by approximately 40 to 50 percent and shorten drivers' reaction times to brake in response to emergent events occurring at intersections. Moreover, drivers' reaction times to brake in response to the audio warning system were significantly shorter than in response to the visual warning system in the cross-traffic from right scenario. In addition, speeds were reduced in all 3 scenarios and deceleration rates increased in the cross-traffic from left and right turn against scenario under the influence of ICWS. CONCLUSIONS: In general, the results provide overall support for ICWSs based on the DSRC technology concept. The broader implications of the research are discussed. PMID- 21972865 TI - Effects of countdown timers on driver behavior after the yellow onset at Chinese intersections. AB - OBJECTIVES: Few studies have focused on the effect of countdown timers at signalized intersections in China, where such timers are widely deployed for their perceived benefits of increased safety and capacity. This study examines the effect of countdown timers on driver behavior during the yellow interval. METHOD: Signal phasing and traffic operations were videotaped at 4 comparable signalized intersections under normal conditions. Microscopic details were extracted manually at 25 Hz to yield 24 h of data on onset time of the yellow, onset time of the red, driver location and actions after the onset of the yellow, red light-running violations, etc. For comparable intersections with and without countdown timers, driver behavior measured by driver decision (stop or go) and vehicle entry time (when the vehicle crosses the stop line) were analyzed using binary logistical regression (BLR) and a nonparametric test, respectively. RESULTS: The results suggest that countdown timers can indeed influence driver behaviors, in terms of decisions to stop or cross the intersection as well as the distribution of vehicle entry times. There was a strong correlation between the presence of countdown timers and an increase in red light violations. CONCLUSION: Countdown timers may lead to increased entrance into the intersection during the later portions of the yellow and even the red. This alarming finding calls for further research as well as for serious consideration before the field deployment of countdown timers. PMID- 21972866 TI - Hybrid nanostructures for enhanced light-harvesting: plasmon induced increase in fluorescence from individual photosynthetic pigment-protein complexes. AB - We studied the optical response from more than 13, 000 individual photosynthetic pigment-protein complexes interacting with spherical gold nanoparticles. The nanodots were arranged in a quasi-hexagonal array by diblock copolymer micellar nanolithography. Exciting the proteins within the spectral range of the nanoparticles' plasmon resonance yields a clear enhancement of the protein fluorescence intensity, whereas excitation far out of the plasmon resonance features no effect. This result indicates a strategy for the construction of efficient hybrid light-harvesting devices. PMID- 21972867 TI - Photosynthetic acclimation to light in woody and herbaceous species: a comparison of leaf structure, pigment content and chlorophyll fluorescence characteristics measured in the field. AB - Acclimation of foliage photosynthetic properties occurs with varying time kinetics, but structural, chemical and physiological factors controlling the kinetics of acclimation are poorly understood, especially in field environments. We measured chlorophyll fluorescence characteristics, leaf total carotenoid (Car), chlorophyll (Chl) and nitrogen (N) content and leaf dry mass per area (LMA) along vertical light gradients in natural canopies of the herb species, Inula salicina and Centaurea jacea, and tree species, Populus tremula and Tilia cordata, in the middle of the growing season. Presence of stress was assessed on the basis of night measurements of chlorophyll fluorescence. Our aim was to compare the light acclimation of leaf traits, which respond to light availability at long (LMA and N), medium (Chl a/b ratio, Car/Chl ratio) and short time scales (fluorescence characteristics). We found that light acclimation of nitrogen content per unit leaf area (N(area)), chlorophyll content per unit dry mass (Chl(mass)) and Chl/N ratio were related to modifications in LMA. The maximum PSII quantum yield (F(v) /F(m)) increased with increasing growth irradiance in I. salicina and P. tremula but decreased in T. cordata. Leaf growth irradiance, N content and plant species explained the majority of variability in chlorophyll fluorescence characteristics, up to 90% for steady-state fluorescence yield, while the contribution of leaf total carotenoid content was generally not significant. Chlorophyll fluorescence characteristics did not differ strongly between growth forms, but differed among species within a given growth form. These data highlight that foliage acclimation to light is driven by interactions between traits with varying time kinetics. PMID- 21972868 TI - Relaxation behavior study of ultrasmall superparamagnetic iron oxide nanoparticles at ultralow and ultrahigh magnetic fields. AB - Ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) have attracted attention because of their current and potential usefulness as contrast agents for magnetic resonance imaging (MRI) and nuclear magnetic resonance (NMR). USPIOs are usually used for their significant capacity to produce predominant proton relaxation effects, which result in signal reduction. However, most previous studies that utilized USPIOs have been focused on the relaxation behavior at commonly used magnetic fields of clinical MRI systems (typically 1-3 T). In this paper, magnetic relaxation processes of protons in water surrounding the USPIOs are studied at ultralow (<=10 mT) and ultrahigh magnetic fields (14.1 T). USPIOs used in our experiments were synthesized with a core size of 6 nm, and transferred from organic to water by ligand exchange. The proton spin-lattice relaxation time (T(1)) and spin-spin relaxation time (T(2)) were investigated at ultralow (212 MUT for T(2) and 10 mT for T(1)) and at 14.1 T with different iron concentrations. At all of the fields, there is a linear relationship between the inverse of relaxation times and the iron concentration. The spin-spin relaxivity (r(2)) at 14.1 T is much larger than that value of the ultralow field. At ultralow field, however, the spin-lattice relaxivity (r(1)) is larger than the r(1) at ultrahigh field. The results provide a perspective on potential in vivo and in vitro applications of USPIOs in ultralow and ultrahigh field NMR and MRI. PMID- 21972869 TI - Primary cutaneous CD30-positive anaplastic large cell lymphoma in a 16-year-old girl. PMID- 21972870 TI - Tetrahydrozoline (Visine(r)) concentrations in serum and urine during therapeutic ocular dosing: a necessary first step in determining an overdose. AB - INTRODUCTION: No information exists on therapeutic or toxic concentrations of tetrahydrozoline, which has been reported to be used in drug facilitated sexual assaults. The primary aim of this investigation was to establish baseline therapeutic serum and urine concentrations in a sample of healthy volunteers. METHODS: Ten healthy volunteers consented to have two drops of Original Visine(r) eye drops (0.05% tetrahydrozoline solution) placed directly into the conjunctival sac of each eye, 30 s apart, at times 0, 4, 8, and 12 h. Blood and urine samples were then collected at 2, 5, 9, 13, and 24 h post-application and analyzed for concentrations. Tetrahydrozoline concentrations are described using measures of central tendency and dispersion at each time point, with predictions of serum and urine concentrations over time calculated using a linear mixed effects regression model. RESULTS: Tetrahydrazoline concentrations were detectable in both serum and urine after therapeutic ocular administration. The mean serum half-life of tetrahydrozoline was approximately 6 h. Systemic absorption varied among subjects, with the maximum serum concentrations ranging from 0.068 to 0.380 ng/ml. At 24 h, all patients had detectable urine concentrations of tetrahydrozoline (range = 13?210 ng/ml). CONCLUSION: When used as directed by the manufacturer for therapeutic ocular administration, tetrahydrozoline concentrations were detectable in both serum and urine up to 12 h after the last administered dose. A concentration greatly exceeding the 95% confidence interval of drug present during therapeutic ocular use may be suggestive of illegal adulterant use or accidental or suicidal overdose. PMID- 21972871 TI - Periorbital oedema and treatment-resistant hypertension as rare side effects of clozapine. PMID- 21972872 TI - Guest Editorial: Shifting sexuality among lowland Thai women. PMID- 21972873 TI - Gender and class differences in young people's sexuality and HIV/AIDS risk-taking behaviours in Thailand. AB - This study examines gender and class differences in young people's beliefs about sexuality and HIV/AIDS risk-taking behaviours in Thailand. Sixty young people aged 15-19, divided equally by gender and socioeconomic background, participated in focus groups and in-depth interviews. Four topics were explored: the differences between 'good' and 'bad' girls/boys; young people's perceptions of sexuality; social class variations in young people's knowledge of HIV/AIDS and perceptions of risk; and the most influential institutions shaping young people's sexual attitudes. Results showed that young people screened potential sexual partners utilizing an image of 'good girls/boys' as potential HIV/AIDS-free partners; young people defined sexuality in terms of love/sexual relationships, premarital sex, promiscuity, and virginity; and HIV/AIDS awareness varied according to class. Young people of all classes failed to demonstrate an in-depth understanding of how they can contract AIDS. They neither viewed themselves as being in an at-risk group, nor considered their sexual behaviours to be at-risk behaviours. Finally, family, friends, and mass media were reported to be among the most influential institutions shaping young people's sexual attitudes. In the struggle against HIV/AIDS, these institutions together with health education not only protect but also can empower young people in Thailand. PMID- 21972874 TI - The fluidity of Thai women's gendered and sexual subjectivities. AB - This paper reports on an ethnographic study of gender and sexuality as factors within contemporary Thai factory women's subjectivities. Competing discourses of what it means to be a woman in contemporary Thai society make women's self presentations fluid and incoherent. Data from participant-observation and open ended interviews suggest that the fluidity and inconsistency of women's self presentations reflect both their negative experiences and oppression within the Thai patriarchal system, and women's strength and resistance to the normative discourses that oppress them. By naming or reinterpreting experiences and desires in their own terms, Thai factory women can redraw elements of their own lives. PMID- 21972875 TI - Female Sexuality in Thai Discourses about Maechii ('lay nuns'). AB - By examining competing discourses about women who are maechii (or 'lay nuns') in Buddhist Thai society, this paper demonstrates that, although maechii vow to be celibate, social constructions of their role are grounded in sexuality. The discourses examined are those of the Buddhist canon and Sangha (Order of Monkhood), the Thai Maechii Institute, the mass media, and the government. The analysis is supplemented with field observations and interviews with monks, maechii, and lay persons. Findings suggest that maechii comprise an ambiguous category linguistically, Buddhistically, and in terms of their sexuality. Case studies of the founders of nunneries conducted in ChiangMai indicate that maechii leaders have been resisting the prevalent views that most maechii are social misfits, yet also are capable of undermining monks' celibacy and, by extension, the larger social order. The analysis contributes to the understanding of the interconnectedness of gender and sexuality in contemporary Thai society. PMID- 21972876 TI - Mobility, sexual networks and exchange among bodabodamen in southwest Uganda. AB - In order to examine the sexual behaviour of a highly mobile social group, qualitative data and quantitative data were elicited from 212 private motorbike taxi-men, locally called bodabodamen, from two study sites in Masaka, Uganda. Selection criteria were availability and willingness to participate in the study. Research techniques employed were a questionnaire, focus group discussions, in depth interviews and case studies. Findings indicate that bodabodamen are a highly mobile group who engage in frequent seasonal rural-urban migration. Consequent to this, bodabodamen have a wide network of both occasional and regular sexual partnerships. Both serial and concurrent multiple partnerships are with adults, youths, widows, students, sugar-mummies, barmaids, commercial sex workers, tailors. Exchange plays a significant role in sexual negotiations but the act of giving to a sexual partner is ambivalent in its social interpretation. Since bodabodamen have regular access to cash, they have higher bargaining power for sex. Implications for HIV/AIDS prevention are discussed. PMID- 21972877 TI - Why is teenage pregnancy conceptualized as a social problem? A review of quantitative research from the USA and UK. AB - To explore why teenage pregnancy is regarded by researchers from the USA and UK as a major social problem, a systematic review was conducted of published research on the social influences on teenage pregnancy. Papers published in the USA and UK between 1981 and 2000 were examined with respect to samples, social influences and outcomes. UK studies often justified investigating teenage pregnancy in terms of health. Research from the USA more often viewed teenage pregnancy as problematic because of associated welfare expenditure. A few studies from the USA regarded teenage parenting as mediating the intergenerational transmission of poverty. Such studies often focused on Black and minority ethnic populations. Most research considered economic and cultural influences, with a bias in research from the USA on cultural factors, and in the UK on economic factors. Overall, there were significant differences between research in the USA and UK. These may have arisen from a combination of political, religious and research design factors. PMID- 21972879 TI - Medical pluralism in the andes. PMID- 21972880 TI - What's wrong with addiction? PMID- 21972881 TI - Sexual Selections: What We Can and Can't Learn about Sex from Animals. PMID- 21972882 TI - Effect of insulation material in aging pacing leads: comparison of impedance and other electricals: time-dependent pacemaker insulation changes. AB - BACKGROUND: There has been concern over declining bipolar (BP) impedance (Z) in aging polyurethane (PU) cardiac pacing leads. Subsequently, a prospective study was conducted comparing BP Z, threshold (Th), and R-wave sensing amplitude of 55D PU-insulated (Model 4024, Medtronic, Inc., Minneapolis, MN, USA) and silicone insulated (Model 5024) leads. METHODS: This study was initiated by The Iowa Heart Center. Patients with Model 4024 (N = 162) or 5024 (N = 120) pacing leads with at least 6 years implant time were enrolled and followed for an additional 5 years. RESULTS: There was a significant drop in the mean BP Z for the Model 4024 population, between enrollment (6 years) and the final endpoint (11 years), which was in contrast to the Model 5024 which did not see a significant drop in its mean BP Z for this same period. The trend difference seen in the means between the two models was statistically significant (P < 0.0001). In addition, a statistically significant relationship was found between dropping BP Z and rising Th (P < 0.0001). The analysis showed that if BP Z dropped below 200 ohms, the probability of having a >3X increase over baseline, in Th at 2.5 V, increases from approximately 3-7% to as high as 30%. CONCLUSIONS: A significant drop in BP Z observed in the PU-insulated Model 4024 lead was not present in the silicone insulated Model 5024 lead. The statistically significant relationship between dropping BP Z and rising Th helps to understand how to better manage patients with aging leads. PMID- 21972883 TI - Clinical outcome of spontaneous non-aneurysmal subarachnoid hemorrhage in 108 patients. AB - BACKGROUND: The cause of spontaneous subarachnoid hemorrhage (SAH) is unknown in 15% of cases; idiopathic SAH has a better prognosis than aneurysmal SAH. When bleeding is confined to the perimesencephalic cisterns, SAH has an especially benign course. METHODS: We retrospectively studied 108 patients admitted for spontaneous non-aneurysmal SAH between 1991 and 2004. We divided patients into two groups according to the bleeding pattern at cranial CT: perimesencephalic pattern (n=60) and aneurysmal pattern (n=48). We included only patients in whom no source of bleeding was detected at angiography; patients with aneurysmal pattern underwent at least two angiographic examinations. Mean follow-up was 5.5years; follow-up consisted of telephone interview in 84.7% of patients. RESULTS: All but one patient with perimesencephalic pattern were classified as grade I or II on the Hunt and Hess scale; the exception was the only patient in this group with a complication (hydrocephalus), who was classified as grade IV. Three-quarters of the patients with aneurysmal pattern were classified as grade I or II on the Hunt and Hess scale; 5 patients presented with hydrocephalus that required drainage and 2 with vasospasms without repercussions. No rebleeding or long-term complications were observed in either group. CONCLUSIONS: Non aneurysmal SAH with a perimesencephalic pattern of bleeding has a benign course and excellent short-term and long-term prognosis. Patients with non-aneurysmal SAH with an aneurysmal pattern of bleeding have more complications, and the initial clinical situation has a significant impact on their prognosis. PMID- 21972884 TI - The influence of patient position on withdrawal force of thoracic epidural catheters. AB - We investigated the forces required to remove thoracic epidural catheters to determine the effect of patient position on removal. Eighty-four patients undergoing open thoracotomy and thoracic patient-controlled epidural analgesia were enrolled. Catheterisation was performed under fluoroscopic guidance before surgery, and the patients were allocated to one of three position groups for removal: prone; sitting; and lateral. On the third postoperative day, the peak tension during withdrawal in the assigned position was measured. No differences in mean (SD) forces were found between groups: prone 1.61 (0.39) N, supine 1.62 (0.61) N and lateral 1.36 (0.56) N (p = 0.140). The withdrawal forces required to remove thoracic epidural catheters were not affected by the position. Thus, the position for removal can be determined by patient's choice and clinical judgement. PMID- 21972885 TI - Synthesis and characterization of poly(N-hydroxyethylacrylamide) for long-term antifouling ability. AB - Development of biomaterials with long-term biocompatibility, durability, and stability remains a critical challenge for biomedical devices. Here, we synthesize, characterize, and graft poly(N-(2-hydroxyethyl)acrylamide) (polyHEAA) onto both gold surfaces and gold nanoparticles (AuNPs) via surface-initiated atom transfer radical polymerization (SI-ATRP) to form a stable antifouling coating to resist nonspecific protein adsorption and bacterial attachment. Surface plasmon resonance (SPR) results demonstrate that all of polyHEAA brushes coated on the gold substrate at a wide range of film thickness of ~10-40 nm can achieve almost zero protein adsorption from undiluted blood plasma and serum for 1 h, while static bacteria assay results show that polyHEAA brushes prohibit long-term bacterial colonization by Staphylococcus epidermidis and Escherichia coli RP437 up to 3 days. Moreover, the polyHEAA-coated AuNPs with different diameters remain their hydrodynamic sizes unchanged in human blood plasma and serum for up to 7 days. All these data indicate that polyHEAA can serve as promising biomaterials with long-term biocompatibility and durability suitable for applications in complex biological media. PMID- 21972886 TI - Litter effects on seedling establishment interact with seed position and earthworm activity. AB - Seedling establishment is influenced by litter cover and by seed predators, but little is known about interactions between these two factors. We tested their effects on emergence of five typical grassland species in a microcosm experiment. We manipulated the amounts of grass litter, seed sowing position and earthworm activity to determine whether: (i) the protective effect of litter against seed predation depends on cover amount and seed sowing position, i.e., on top or beneath litter; (ii) seed transport by earthworms changes the effect of seed sowing position on seedling emergence; and (iii) seeds transported into deeper soil layers by earthworms are still germinable. Litter cover and presence of earthworms lowered seedling emergence. The impact of seed position increased with seed size. Emergence of large-seeded species was reduced when sown on the surface. Additionally, we found an important seed position * earthworm interaction related to seed size. Emergence of large-seeded species sown on top of the litter was up to three times higher when earthworms were present than without earthworms. Earthworms also significantly altered the depth distribution of seeds in the soil and across treatments: on average 6% of seeds germinated after burial. In contrast to the seed position effect, we found no size effect on mobility and germinability of seeds after burial in the soil. Nevertheless, the fate of different-sized seeds may differ. While burial will remove large seeds from the regeneration pool, it may enhance seed bank build up in small-seeded species. Consequently, changes in the amount of litter cover and the invertebrate community play a significant role in plant community composition. PMID- 21972887 TI - Protein-ligand structure and electronic coupling of photoinduced charge-separated state: 9,10-anthraquinone-1-sulfonate bound to human serum albumin. AB - To elucidate how the protein-ligand docking structure affects electronic interactions in the electron-transfer process, we have analyzed time-resolved electron paramagnetic resonance spectra of photoinduced charge-separated (CS) states generated by light excitation of 9,10-anthraquinone-1-sulfonate (AQ1S(-)) bound to human serum albumin at a hydrophobic drug-binding region. The spectra have been explained in terms of the triplet-triplet electron spin polarization transfer model to determine both the geometries and the exchange couplings of the CS states of AQ1S(2-*)-histidine-242 radical cation (H242(+*)) and AQ1S(2-*) tryptophan-214 radical cation (W214(+*)). For the CS state of the former, it has been revealed that, due to the orthogonal relationship between the singly occupied molecular orbitals of AQ1S(2-*) and H242(+*), the electronic coupling (5.4 cm(-1)) is very weak, contributing to the prevention of energy-wasting charge recombination, even at a contact edge-to-edge separation. PMID- 21972889 TI - Method of applying internal standard to dried matrix spot samples for use in quantitative bioanalysis. AB - A novel technique is presented that addresses the issue of how to apply internal standard (IS) to dried matrix spot (DMS) samples that allows the IS to integrate with the sample prior to extraction. The TouchSpray, a piezo electric spray system, from The Technology Partnership (TTP), was used to apply methanol containing IS to dried blood spot (DBS) samples. It is demonstrated that this method of IS application has the potential to work in practice, for use in quantitative determination of circulating exposures of pharmaceuticals in toxicokinetic and pharmacokinetic studies. Three different methods of IS application were compared: addition of IS to control blood prior to DBS sample preparation (control 1), incorporation into extraction solvent (control 2), and the novel use of TouchSpray technology (test). It is demonstrated that there was no significant difference in accuracy and precision data using these three techniques obtained using both manual extraction and direct elution. PMID- 21972888 TI - Composition of epiphytic bacterial communities differs on petals and leaves. AB - The epiphytic bacterial communities colonising roots and leaves have been described for many plant species. In contrast, microbiologists have rarely considered flowers of naturally growing plants. We identified bacteria isolated from the surface of petals and leaves of two plant species, Saponaria officinalis (Caryophyllaceae) and Lotus corniculatus (Fabaceae). The bacterial diversity was much lower on petals than on leaves of the same plants. Moreover, the bacterial communities differed strongly in composition: while Pseudomonadaceae and Microbacteriaceae were the most abundant families on leaves, Enterobacteriaceae dominated the floral communities. We hypothesise that antibacterial floral volatiles trigger the low diversity on petals, which is supported by agar diffusion assays using substances emitted by flowers and leaves of S. officinalis. These results suggest that bacteria should be included in the interpretation of floral traits, and possible effects of bacteria on pollination are proposed and discussed. PMID- 21972890 TI - Chrysin protects mice from Staphylococcus aureus pneumonia. AB - AIM: To elucidate the effect of chrysin on alpha-haemolysin production by Staphylococcus aureus and protection against pneumonia in a murine model. METHODS AND RESULTS: Haemolysis, Western blot and real-time RT-PCR assays were performed to evaluate the effect of chrysin on alpha-haemolysin secretion by Staph. aureus. The efficacy of chrysin against human alveolar epithelial cell injury by alpha haemolysin was tested using live/dead staining or by measuring lactate dehydrogenase activity. Furthermore, we determined the protective effect of chrysin against Staph. aureus pneumonia through histopathology experiments in a mouse model. The production of alpha-haemolysin by Staph. aureus was inhibited when presented with an increasing subinhibitory concentration of chrysin in vitro. Consistent with this result, chrysin prevented alpha-haemolysin-mediated cell injury and protected mice from Staph. aureus pneumonia. CONCLUSIONS: Chrysin is a potent inhibitor of alpha-haemolysin expression by Staph. aureus, and it conferred a significant degree of protection against Staph. aureus pneumonia. SIGNIFICANCE AND IMPACT OF STUDY: The chrysin-mediated inhibition of alpha haemolysin production and protection against Staph. aureus pneumonia may offer a new strategy in combating pathogen infections. PMID- 21972891 TI - Rapid floral senescence following male function and breeding systems of some tropical orchids. AB - No comparative study of floral senescence following male function among a range of tropical orchid genera has previously been undertaken. The timing and pattern of floral senescence and occurrence of fruit formation were studied following self-, geitonogamous and cross-pollination in 14 epiphytic and two terrestrial orchid species to determine their breeding system and assess the occurrence of floral abscission following pollinaria removal. Both pollination and pollinaria removal caused rapid floral senescence, and the pattern and timing of the floral changes were the same in all treatments. Six Dendrobium species and Pelatantheria insectifera were self-incompatible (SI) and eight other species, including one terrestrial species, were self-compatible (SC). Capsules produced from outcrossing in four SC species, Phalaenopsis cornu-cervi, Eria pubescens, Cleisostoma appendiculatum and Arundina graminifolia, were larger and heavier than those produced after selfing. Reductions in flower life span following pollinaria removal were positively correlated with flower size and longevity of unpollinated flowers but not with position in the inflorescence or nature of the breeding system. Rapid flower senescence following pollinaria removal reported here suggests that it may be widespread in tropical species. The significant association of the response with size of flowers and inflorescences among the species studied suggests that the cost of flower maintenance outweighs the benefit of remaining open for female function after pollinaria have been removed. Both SC and SI species were found among tropical orchids, but variation in capsule size following self- and cross-pollination indicates that there may be a reduction in seed production following selfing, even in SC species, and that fruit formation alone should not be taken as reliable evidence of full self compatibility. PMID- 21972892 TI - A simple technique to reduce the risk of irreversible gingival recession after the final impression. AB - The chemicomechanical method is the most common tissue displacement technique used to facilitate the final impression for fixed dental prostheses. The article describes a simple technique to minimize the risk of developing gingival irreversible recession because of tissue displacement cords. PMID- 21972893 TI - Intracardiac expression of markers of endothelial damage/dysfunction, inflammation, thrombosis, and tissue remodeling, and the development of postoperative atrial fibrillation. AB - BACKGROUND: Atrial fibrillation (AF) is a common complication of coronary artery bypass grafting (CABG), and may have an inflammatory and/or thrombotic etiology. We sought to determine the expression of inflammatory (interleukin [IL]-6), thrombotic (tissue factor and von Willebrand factor [VWF]) and remodeling (matrix metalloproteinase [MMP]-9 and tissue inhibitor of metalloproteinase [TIMP]-1) markers by left atrial appendage (LAA) and right atrial appendage (RAA) tissue in the prediction of postoperative AF. We determined whether the tissue expression of markers of certain different pathophysiologic mechanisms predicted the development of AF after CABG. METHODS: LAA and RAA tissue was excised during CABG in 100 patients free of AF and inflammation. Tissue marker expression was quantified by immunohistochemistry and was related to 30-day postoperative AF. RESULTS: Overall, there were no significant differences in staining intensity of any marker between LAA tissue and RAA tissue. However, more intense expression of VWF by LAA tissue predicted the 30 patients with postoperative AF as compared with those free of AF (P = 0.006). IL-6, MMP-9 and TIMP-1 expression by RAA and LAA epicardial tissue was stronger than expression by endocardium or cardiomyocytes (all P < 0.025) but failed to predict AF. CONCLUSION: In this study, one of the largest to investigate tissue expression of pathophysiologic markers in relation to postoperative AF, we show that more intense expression of VWF by LAA tissue is a significant predictor of postoperative AF. This points towards a possible role of endothelial damage/dysfunction (as reflected by VWF changes) in the pathogenesis of postoperative AF. PMID- 21972894 TI - Differences in biomechanical features of tongue pressure production between articulation and swallow. AB - Summary The purpose of this study was to compare the tongue pressure against the hard palate during the articulation of a monosyllable with that during swallowing. The participants were 20 healthy adults without swallowing or articulation disorder (10 men and 10 women, mean age +/- standard deviation: 22.5 +/- 0.9 years). Tongue pressure during articulation of [ki] (articulatory pressure) and during dry swallowing (swallowing pressure) was recorded by a 0.1 mm-thick sensor sheet with five measuring points attached to the hard palate. Biomechanical parameters such as maximal magnitude, duration, integrated value and slope gradient were compared between articulatory pressure and swallowing pressure at each measuring point. Although swallowing pressure was produced at each measuring point, articulatory pressure was found only in the posterior circumferential parts of the hard palate and was smaller in magnitude (14.9-16.7% of swallowing pressure) and integrated value, which meant the amount of work by tongue pressing (7.0-7.9%), shorter in duration (26.6-31.8%) and shallower in slope gradient, which meant the speed of tongue pressing (26.9-27.4%). Maximal magnitude was closely correlated with duration (R(2) = 0.386) and slope gradient (R(2) = 0.843) for articulatory pressure. These results first show the biomechanical differences between articulation and swallowing in terms of tongue contact with the hard palate. The findings suggest that tongue pressure measurement might be a useful investigation for patients with tongue motor disorder. PMID- 21972896 TI - Association of MSX1 799 G>T variant with nonsyndromic cleft lip/palate in South Indian adolescent patients. AB - BACKGROUND: Nonsyndromic cleft lip/palate (NSCLP) is a common congenital anomaly with significant medical, psychological, social, and economic ramifications. It is an example of complex genetic trait. There is sufficient evidence to hypothesise that disease locus for this condition can be identified by candidate genes. The purpose of this study was to test whether MSX1 (799 G>T) gene variant was involved in the aetiology of NSCLP. METHODS: Blood samples were collected with informed consent from 25 subjects having NSCLP and 25 controls. Genomic DNA was extracted from the blood samples, polymerase chain reaction was performed (PCR), and digestion products were evaluated. RESULTS: The results showed a positive correlation between MSX1 (799 G>T) gene variant and NSCLP patients. CONCLUSION: MSX1 (799 G>T) gene variants may be a good screening marker for NSCLP. PMID- 21972895 TI - Mice deficient in endothelin-converting enzyme-2 exhibit abnormal responses to morphine and altered peptide levels in the spinal cord. AB - An increasing body of evidence suggests that endothelin-converting enzyme-2 (ECE 2) is a non-classical neuropeptide processing enzyme. Similar to other neuropeptide processing enzymes, ECE-2 exhibits restricted neuroendocrine distribution, intracellular localization, and an acidic pH optimum. However, unlike classical neuropeptide processing enzymes, ECE-2 exhibits a non-classical cleavage site preference for aliphatic and aromatic residues. We previously reported that ECE-2 cleaves a number of neuropeptides at non-classical sites in vitro; however its role in peptide processing in vivo is poorly understood. Given the recognized roles of neuropeptides in pain and opiate responses, we hypothesized that ECE-2 knockout (KO) mice might show altered pain and morphine responses compared with wild-type mice. We find that ECE-2 KO mice show decreased response to a single injection of morphine in hot-plate and tail-flick tests. ECE 2 KO mice also show more rapid development of tolerance with prolonged morphine treatment and fewer signs of naloxone-precipitated withdrawal. Peptidomic analyses revealed changes in the levels of a number of spinal cord peptides in ECE-2 KO as compared to wild-type mice. Taken together, our findings suggest a role for ECE-2 in the non-classical processing of spinal cord peptides and morphine responses; however, the precise mechanisms through which ECE-2 influences morphine tolerance and withdrawal remain unclear. PMID- 21972897 TI - Bayes and blickets: effects of knowledge on causal induction in children and adults. AB - People are adept at inferring novel causal relations, even from only a few observations. Prior knowledge about the probability of encountering causal relations of various types and the nature of the mechanisms relating causes and effects plays a crucial role in these inferences. We test a formal account of how this knowledge can be used and acquired, based on analyzing causal induction as Bayesian inference. Five studies explored the predictions of this account with adults and 4-year-olds, using tasks in which participants learned about the causal properties of a set of objects. The studies varied the two factors that our Bayesian approach predicted should be relevant to causal induction: the prior probability with which causal relations exist, and the assumption of a deterministic or a probabilistic relation between cause and effect. Adults' judgments (Experiments 1, 2, and 4) were in close correspondence with the quantitative predictions of the model, and children's judgments (Experiments 3 and 5) agreed qualitatively with this account. PMID- 21972899 TI - Superfast-response and ultrahigh-power-density electromechanical actuators based on hierarchal carbon nanotube electrodes and chitosan. AB - Here we report a novel single-walled carbon nanotube (SWNT) based bimorph electromechanical actuator, which consists of unique as-grown SWNT films as double electrode layers separated by a chitosan electrolyte layer consisting of an ionic liquid. By taking advantage of the special hierarchical structure and the outstanding electrical and mechanical properties of the SWNT film electrodes, our actuators show orders-of-magnitude improvements in many aspects compared to previous ionic electroactive polymer (i-EAP) actuators, including superfast response (19 ms), quite wide available frequency range (dozens to hundreds of Hz), incredible large stress generating rate (1080 MPa/s), and ultrahigh mechanical output power density (244 W/kg). These remarkable achievements together with their facile fabrication, low driving voltage, flexibility, and long durability enable the SWNT-based actuators many applications such as artificial muscles for biomimetic flying insects or robots and flexible deployable reflectors. PMID- 21972898 TI - Isotope-induced desymmetrization can mimic isotopic perturbation of equilibria. On the symmetry of bromonium ions and hydrogen bonds. AB - The desymmetrizing effect of isotopic substitution on the geometry of otherwise symmetrical structures can be surprisingly large when there is anharmonic coupling between a desymmetrizing mode and modes whose zero-point energies are strongly isotope-dependent. This phenomenon is found to account for experimental observations that had been previously interpreted as implying asymmetry in bromonium ions and in hydrogen phthalate ions in aprotic solvents. The unlabeled structures are concluded to have the higher symmetry found in computed structures. Great care must be taken in applying isotopic perturbation as a test of asymmetry. PMID- 21972901 TI - Application of quantitative 19F and 1H NMR for reaction monitoring and in situ yield determinations for an early stage pharmaceutical candidate. AB - Quantitative NMR spectrometry (qNMR) is an attractive, viable alternative to traditional chromatographic techniques. It is a fast, easy, accurate, and nondestructive technique which allows an analyst to gain quantitative information about a component mixture without the necessity of authentic reference materials, as is the case with most other analytical techniques. This is ideal for the synthesis of active pharmaceutical ingredients (API) that are in the early stages of development where authentic standards of the analytes may not be available. In this paper, the application of (19)F and (1)H qNMR for reaction monitoring and in situ potency determinations will be discussed for an early stage pharmaceutical candidate with several analytical challenges. These challenges include low UV absorption, low ionization, thermal instability, and lack of authentic reference standards. Quantitative NMR provided quick, fit-for-purpose solutions for process development where conventional separation techniques were limited. PMID- 21972900 TI - Spatio-temporal heterogeneity in Arabidopsis thaliana leaves under drought stress. AB - Using chlorophyll (chl) fluorescence imaging, we studied the effect of mild (MiDS), moderate (MoDS) and severe (SDS) drought stress on photosystem II (PSII) photochemistry of 4-week-old Arabidopsis thaliana. Spatio-temporal heterogeneity in all chl fluorescence parameters was maintained throughout water stress. After exposure to drought stress, maximum quantum yield of PSII photochemistry (F(v)/F(m)) and quantum efficiency of PSII photochemistry (Phi(PSIotaIota)) decreased less in the proximal (base) than in the distal (tip) leaf. The chl fluorescence parameter F(v) /F(m) decreased less after MoDS than MiDS. Under MoDS, the antioxidant mechanism of A. thaliana leaves seemed to be sufficient in scavenging reactive oxygen species, as evident by the decreased lipid peroxidation, the more excitation energy dissipated by non-photochemical quenching (NPQ) and decreased excitation pressure (1-q(p)). Arabidopsis leaves appear to function normally under MoDS, but do not seem to have particular metabolic tolerance mechanisms under MiDS and SDS, as revealed by the level of lipid peroxidation and decreased quantum yield for dissipation after down regulation in PSII (Phi(NPQ)), indicating that energy dissipation by down regulation did not function and electron transport (ETR) was depressed. The simultaneous increased quantum yield of non-regulated energy dissipation (Phi(NO)) indicated that both the photochemical energy conversion and protective regulatory mechanism were insufficient. The non-uniform photosynthetic pattern under drought stress may reflect different zones of leaf anatomy and mesophyll development. The data demonstrate that the effect of different degrees of drought stress on A. thaliana leaves show spatio-temporal heterogeneity, implying that common single time point or single point leaf analyses are inadequate. PMID- 21972902 TI - Bcl-2 suppresses hydrogen peroxide-induced programmed cell death via OsVPE2 and OsVPE3, but not via OsVPE1 and OsVPE4, in rice. AB - Hydrogen peroxide (H(2)O(2)) is known to be a key player in apoptosis in animals. The components and pathways regulating H(2)O(2)-induced programmed cell death in plants, however, remain largely unknown. In the present study, rice transgenic lines overexpressing Bcl-2, a human apoptotic suppressor, were obtained. These transgenic lines showed increased tolerance to high levels of H(2)O(2), resulting in increased seed germination rates, root elongation, root tip cell viability and chlorophyll retention compared to control lines. In the control lines, treatment with H(2)O(2) resulted in DNA laddering and a clear terminal transferase dUTP nick end labeling signal, which are the hallmarks of programmed cell death. However, this effect was not detected in the Bcl-2-overexpressing transgenic lines. Further investigations indicated that Bcl-2 suppressed H(2)O(2)-induced programmed cell death but did not inhibit stress-elicited reactive oxygen species production in rice. RT-PCR revealed that the expression of the two vacuolar processing enzyme genes (i.e. OsVPE2 and OsVPE3) was dramatically induced by H(2)O(2) in the wild-type line but not in the Bcl-2-overexpressing line. Moreover, treatment with H(2)O(2) resulted in the disruption of the vacuolar membrane in the wild-type line. The expression levels of OsVPE1 and OsVPE4 did not significantly differ between the wild-type line and the transgenic line that was treated or untreated with H(2)O(2). The similar roles of Bcl-2 and OsVPEs during endogenous reactive oxygen species-triggered programmed cell death were also confirmed by NaCl stress in rice. To our knowledge, the present study is the first to demonsatrate that Bcl-2 overexpression inhibits H(2)O(2)-induced programmed cell death and enhances H(2)O(2) tolerance. We propose that Bcl-2 overexpression in rice suppresses the transcriptional activation of OsVPE2 and OsVPE3, but not of OsVPE1 or OsVPE4. PMID- 21972903 TI - Life-circumstances, working conditions and HIV risk among street and nightclub based sex workers in Lusaka, Zambia. AB - The principal objective of this study was to conduct formative research among sex workers in Lusaka, Zambia, to understand how sex workers' perceptions of their personal identity influences safer sex practices. In-depth interviews were conducted with 20 sex workers in Lusaka, Zambia, including both nightclub and street-based sex workers. Findings indicate important differences of self perception and identity between nightclub-based sex workers and street-based sex workers. The latter have a professional identity and are willing to be publicly acknowledged as sex workers. This makes it easier for them to convince clients to use condoms. In contrast, nightclub-based sex workers are less likely to wish to be identified as sex workers. They are motivated by the desire to meet a man who will perhaps marry them and change their lives. As a consequence, they do not publicly acknowledge their risk of STI/HIV infection and many go against their better judgement by not using condoms. Factors such as the stigmatization of sex work, the harassment of sex workers and the lack of protection available to them interact with sex workers' perceptions of their personal identities and influence their ability to take precautions during high-risk sexual encounters. PMID- 21972904 TI - Stress, trauma, and risky sexual behaviour among American Indians in young adulthood. AB - This paper examines the relationship of risky sexual behaviour to stress and trauma-often the mediators of the content and structure of everyday life-among young American Indians. School, work, social life, and home life bring about demands and stresses for youth; choices young people make may depend on the quantity and content of those demands. Traumatic events or highly distressing situations may shatter fragile (or even resilient) systems of external and internal support from which youth may draw. American Indians live in some of the most impoverished areas of the country, where everyday life includes a heavy burden of stress and trauma. Using data from a representative sample of youth from a Northern Plains tribe, bivariate and adjusted ordered logit models are used to show that stress and trauma do play a role in the sexual decision-making of young people, especially young women. For example, young women who have experienced a trauma have a 20% probability of having had multiple casual partners in the prior year compared to 9% for those who have not experiences a trauma. Types and levels of stress and trauma also make a difference by gender. PMID- 21972905 TI - Saviours and satyrs: ambivalence in narrative meanings of sperm provision. AB - This paper reports on the complex representations of sperm providers in the narratives of donors, recipients and offspring involved in donor-assisted conception. Eighty-seven volunteers from Australia, Canada, UK, USA and Argentina participated in qualitative narrative research. Sperm provision was perceived to be publicly represented as sexualized, provoking both disgust and hilarity; this is interpreted as arising from its association with masturbation and the metaphorical representation of the donor sperm as cuckolding the recipient's husband. Recipients' representations of providers were found to mix gratitude with resentment, embarrassment, and anxiety; their constructions are strongly influenced by the position of the social father. The complex representation of the provider as a genetic father is considered: providers can be seen as threatening the integrity of parents if they become involved in the life of their offspring and abandoning their offspring to confusion and despair if they do not. The research demonstrates that, in spite of its relative frequency and familiarity, donor insemination is still represented ambivalently, including by those who may be said to benefit from it. PMID- 21972906 TI - What do young people want from sex education? The results of a needs assessment from a peer-led sex education programme. AB - This paper presents data on the need for sexual health information and advice of 4353 students aged 13/14 years in 13 English secondary schools. Data were collected by peer educators as part of a sex education programme, and through a questionnaire survey administered by researchers. Data illustrate young people's need for concrete information and advice on issues related to physical development and puberty; transmission of sexually transmitted diseases; accessing and using condoms and other contraception; using sexual health services; managing relationships and dealing with jealousy, love and sexual attraction; how people have sex; sexual pleasure; masturbation; and homosexuality. Differences between the concerns and interests raised by young people and current UK guidance on sex and relationships education are examined, and the implications of these findings for designing future policy and effective school based sex education programmes are discussed. The paper highlights some of the wider social norms around sex and sexuality that influence young people's understanding and sexual behaviour, and the importance of addressing these within sex education is noted. Factors influencing the processes of expressing and assessing needs are explored. PMID- 21972909 TI - Erratum. PMID- 21972907 TI - Patterns of sexual behaviour among secondary school students in Swaziland, southern Africa. AB - Among the many sub-Saharan African countries hardest hit by HIV/AIDS is the Kingdom of Swaziland. In an effort to reduce the spread of HIV, young people are an important group to reach with prevention messages. However, before developing such programmes, it is essential to understand young people's sexual risk behaviours. Students (n=941) from four coeducational secondary schools in Swaziland participated in a cross-sectional survey of sexual behaviours. Results indicate that considerable proportions of young people in this study were sexually experienced, irrespective of gender. Findings also suggest unacceptable high levels of sexual coercion, irrespective of age or gender. While boys may be less likely than girls to experience sexual coercion, being a male in this setting was not a protective factor. No significant differences were found on these variables in relation to location of the schools (rural vs. urban). Implications for developing and implementing HIV prevention programmes are suggested. PMID- 21972910 TI - About the international association for the study of sexuality, culture and society. PMID- 21972911 TI - Classification and differentiation of the genus Peganum indigenous to China based on chloroplast trnL-F and psbA-trnH sequences and seed coat morphology. AB - The genus Peganum (Zygophyllaceae) consists of six species and one subspecies; three of which are distributed in China, P. harmala Linn, P. nigellastrum Bunge and P. multisectum (Maxim.) Bobr. A probable new or intermediate species, Peganum sp., has been suggested in the wild in northwest China. Traditional classification in genus Peganum has focused on hairs on the plant surface. In this study, seed coat characteristics of Peganum species were investigated using light and scanning electron microscopy, demonstrating clear differences in morphology between species. In addition, DNA sequence data from two sequences (chloroplast: trnL-F, psbA-trnH) were used to differentiate Peganum sp. and study polygenetic relationships. Diversity in DNA sequences among Peganum species was found, with inter-specific sequence divergence ranging from 0.6% to 5.6% in psbA trnH, and 0.0% to 1.8% in trnL-F. The variations within species were low: from 0.0% to 0.4% in psbA-trnH and 0.0% to 0.4% in trnL-F. Therefore, Peganum species can now be easily identified as separate entities based on variations in DNA sequences. Phylogenetic trees were constructed from the combined data set for the two gene fragments, and the results indicate that Peganum sp. is monophyletic and sister to P. harmala and P. nigellastrum, while P. multisectum is also monophyletic. DNA data further confirmed that P. multisectum is an independent species and that a new species, Peganum sp., exists within the genus Peganum growing wild in China. PMID- 21972912 TI - 'Rediscovery' revised - the cooperation of Erich and Armin von Tschermak Seysenegg in the context of the 'rediscovery' of Mendel's laws in 1899-1901. AB - The 'rediscovery' of Mendel's laws in 1900 is seen as a turning point in modern research on heredity and genetics. In the first half of the 20th century it was generally held that the 'rediscovery' was made several times, independently, and in a parallel fashion by three European botanists (Carl Correns, Hugo de Vries and Erich von Tschermak-Seysenegg). Since the 1950s, however, serious questions have arisen concerning both the chronology and the specific conceptual contribution of the scientists involved. Not only the independence but also parallelism was analysed in the context of individual research programmes of all three of these scholars. The youngest of them, Austrian botanist Erich von Tschermak-Seysenegg, was excluded from the rank of 'rediscoverers'. It is the aim of this paper to use new archival evidence and add important facts both to the chronology and conceptual framework of Erich von Tschermak-Seysenegg's work. An entirely new aspect is added by identifying his older brother, the physiologist Armin von Tschermak-Seysenegg (1870-1952), as a significant spiritus movens of the events of 1900 and 1901. A selected part of their correspondence, covering the period from 13 March 1898 until 19 November 1901, is made available in transcriptions. PMID- 21972913 TI - Safety and performance of TCI pumps in a magnetic resonance imaging environment. AB - Target controlled infusion (TCI) devices can be associated with significant safety concerns when used during magnetic resonance imaging (MRI). We tested the safety and compatibility of newer TCI systems in a 3-Tesla MRI environment. Two Asena PK and two Agilia TCI pumps were used to administer TCI propofol (at target blood concentrations of 0.5 and 6.0 MUg.ml-1) using the Marsh model under magnetic fields of up to 50 G with a T2-weighted sequence. We assessed the devices for projectile risk, accuracy of drug delivery, alarm function and effects on MR image quality. Both devices did not demonstrate any significant deflection at the tested field strengths, and performed within acceptable limits (cumulative error in total delivered volume < 3%; maximum 10-min interval error < 10%). The Asena pump caused minor artefacts on MR images. The TCI pumps tested perform well and safely implement pharmacokinetic software in a high magnetic field. PMID- 21972914 TI - Monthly variation of multiple sclerosis activity in the southern hemisphere: analysis from 996 relapses in Brazil. AB - BACKGROUND AND PURPOSE: Seasonal variations of multiple sclerosis (MS) activity have been reported, however, most data come from studies in the northern hemisphere. METHODS: We reviewed medical records of MS patients living in Campinas region, Brazil. The first symptoms' date was defined as the relapse month. Climatic information included UV radiation index, median temperature, rainfall, and humidity. RESULTS: Two hundred and nine patients were included. The incidence of relapses was highest in January (11.2%) and December (10.4%) and lowest in November (5.7%) and October (7.0%) (P < 0.015). The months with highest incidence of relapses (December-January) had higher UV radiation index and humidity rates (P = 0.032 and 0.040, respectively). CONCLUSION: Most exacerbations were in the spring/summer transition, which also showed higher UV radiation index and humidity rate. Along with other environmental factors, seasonal fluctuation contributes to MS activity. PMID- 21972915 TI - Statistics, probability, significance, likelihood: words mean what we define them to mean. PMID- 21972916 TI - Severe sodium channel blockade and cardiovascular collapse due to a massive lamotrigine overdose. AB - BACKGROUND: Cardiac arrest due to lamotrigine (LTG) has been reported after co ingestion with bupropion, but severe sodium channel blockade in the absence of other toxins has not been described. We report a case of cardiac arrest and status epilepticus following a massive LTG overdose. CASE REPORT: A 48 year-old female was brought to the ED with seizure-like activity subsequent to ingesting 7.5 g of LTG. Vital signs were HR 131, BP 107/68, T 99.4 degrees F, RR 16. She was intubated in the ED for a low GCS. Initial ECG demonstrated a narrow-complex normal sinus rhythm, and her labs were unremarkable. Three hours after intubation she developed status epilepticus, and a pulseless wide-complex tachycardia. She was aggressively resuscitated during which time pulses were periodically reestablished, but lost each time seizures recurred. She was not stabilized until the convulsions were terminated with vecuronium. Her post-resuscitation ECG demonstrated a junctional tachycardia with a 3 mm R-wave in aVR. The LTG level was 74.7 mcg/ml (therapeutic: 3-14 mcg/ml). Comprehensive LC-MS/MS drug screen was negative for all screened compounds. DISCUSSION: This is the first report of cardiovascular collapse due to LTG with the highest drug concentration to date. CONCLUSION: The degree of neurologic and cardiovascular toxicity seen in this case are novel and illustrate the potential for severe sodium channel blockade after massive LTG poisonings. Drug levels are not clinically relevant in the acute setting due to the time delay in obtaining results, and recurrent seizure activity may be the only clinical finding that precedes severe cardiac toxicity. PMID- 21972917 TI - What is the best age for surgery in drug-resistant mesial temporal lobe epilepsy? PMID- 21972918 TI - Ictal high-frequency oscillations at 80-200 Hz coupled with delta phase in epileptic spasms. AB - Previous studies of epileptic spasms reported that ictal events were associated with high-frequency oscillations (HFOs) or delta waves involving widespread regions. We determined whether ictal HFOs at 80-200 Hz were coupled with a phase of slow-wave, whether ictal slow-waves were diffusely or locally synchronous signals, and whether the mode of coupling between HFOs and slow-wave phases differed between ictal and interictal states. We studied 11 children who underwent extraoperative electrocorticography (ECoG) recording. The phases and amplitudes of slow-waves were measured at the peak of ictal and interictal HFOs in the seizure-onset sites. Ictal HFOs were locked tightly to the phase of slow wave at <=1 Hz. Ictal slow-waves propagated from the seizure-onset site to other regions. In contrast, interictal HFOs in the seizure-onset site were loosely locked to the phase of slow-wave at <=1 Hz but tightly to that of >=3-Hz. Ictal slow-waves coupled with HFOs can be explained as near-field and locally synchronized potentials generated by the neocortex rather than far-field potentials generated by subcortical structures. Ictal slow-waves in epileptic spasms may be generated by a mechanism different from what generates interictal HFOs-slow-wave complexes. PMID- 21972919 TI - Field mapping with nanometer-scale resolution for the next generation of electronic devices. AB - In order to improve the performance of today's nanoscaled semiconductor devices, characterization techniques that can provide information about the position and activity of dopant atoms and the strain fields are essential. Here we demonstrate that by using a modern transmission electron microscope it is possible to apply multiple techniques to advanced materials systems in order to provide information about the structure, fields, and composition with nanometer-scale resolution. Off axis electron holography has been used to map the active dopant potentials in state-of-the-art semiconductor devices with 1 nm resolution. These dopant maps have been compared to electron energy loss spectroscopy maps that show the positions of the dopant atoms. The strain fields in the devices have been measured by both dark field electron holography and nanobeam electron diffraction. PMID- 21972920 TI - Turmerin, the antioxidant protein from turmeric (Curcuma longa) exhibits antihyperglycaemic effects. AB - A wide range of proteinaceous inhibitors are present in plants to protect themselves from hydrolytic enzymes. In this study, turmerin, a water-soluble peptide in turmeric rhizomes, was evaluated for its inhibitory potential against glucosidase and its antioxidant (AO) capacity. Turmerin inhibited alpha-amylase and alpha-glucosidase activities with IC50 values 31 and 192 ug mL-1, respectively. Under the experimental conditions, those values for a standard glucosidase inhibitor, acarbose, were 81 and 296 ug mL-1, respectively. The AO capacity of turmerin was evaluated using in vitro assay systems. Turmerin showed good DPPH (IC50 = 29 ug mL-1) and superoxide (IC50 = 48 ug mL-1) and moderate ABTS (IC50 = 83 ug mL-1) radical scavenging and Fe(II) chelation (IC50 = 101 ug mL-1) capacities. The inhibitory potential showed by turmerin against enzymes linked to type 2 diabetes, as well as its moderate AO capacity, could rationalise the traditional usage of turmeric rhizome preparations against diabetes. PMID- 21972921 TI - Molecular architecture influences the thermally induced aggregation behavior of elastin-like polypeptides. AB - Elastin-like polypeptides are thermally responsive polymers that exhibit phase separation above a transition temperature. The effect of molecular architecture on the temperature responsive behavior of elastin-like polypeptide solutions was investigated by characterization of solutions of three-armed star polypeptides, linear polypeptides, and their mixtures. These biosynthesized polypeptides have precise lengths and amino acid sequences. Transition temperatures were measured as a function of molecular weight and solution concentration and compared to their linear counterparts. Like their linear counterparts, the transition temperature is linearly related to log concentration. A mathematical relationship was used to fit the transition temperature data of different polypeptide lengths to a volume-based concentration using the polymer coil volume. The results of this model suggest that the linear ELP is in a random coil conformation at the transition temperature while the three-armed ELP is in a compact extended coil conformation, consistent with different pathways for aggregation. Solutions containing both trimer and linear constructs have two transition temperatures, further supporting differing aggregation behaviors. PMID- 21972922 TI - Retention of thrombin inhibitory activity by recombinant serpins expressed as integral membrane proteins tethered to the surface of mammalian cells. AB - BACKGROUND: Serpins form a widely distributed protein superfamily, but no integral membrane serpins have been described. OBJECTIVES: To anchor three serpins -alpha(1) -proteinase inhibitor (alpha(1) PI) (M358R), antithrombin (AT), and heparin cofactor II (HCII) - in the plasma membranes of transfected mammalian cells and assess their ability to inhibit thrombin. METHODS: Serpin cDNAs were altered to include N-terminal, non-cleavable plasma membrane-targeting sequences from the human transferrin receptor (TR) (TR-serpin) or the human asialoglycoprotein receptor (AR) (AR-serpin), and used to transfect COS-1 or HEK 293 cells. Cells were analyzed for serpin expression by immunoblotting of subcellular fractions, by immunofluorescence microscopy, or by flow cytometry, with or without exposure to exogenous thrombin; AR-serpins and TR-serpins were also compared with their soluble recombinant counterparts. RESULTS: Both TR alpha(1) PI (M358R) and AR-alpha(1) PI (M358R) were enriched in the integral membrane fraction of transfected COS-1 or HEK 293 cells, and formed inhibitory complexes with thrombin, although less rapidly than soluble alpha(1) PI (M358R). Thrombin inhibition was abrogated by an additional T345R mutation in AR-alpha(1) PI (M358R). Surface-displayed AR-AT also formed serpin-enzyme complexes with thrombin, but to a lesser extent than AR-alpha(1) PI (M358R); AR-HCII inhibitory function was not detected. Immunofluorescence detection and flow cytometric quantification of bound thrombin also supported the status of AR-alpha(1) PI (M358R) and AR-AT as thrombin inhibitors. CONCLUSIONS: Two of three thrombin inhibitory serpins retained functionality when expressed as integral membrane proteins. Our findings could be applied to create and screen hypervariable serpin libraries expressed in mammalian cells, or to confer protease resistance on engineered cells in vivo. PMID- 21972923 TI - Testing the efficiency of Markov chain Monte Carlo with People using facial affect categories. AB - Exploring how people represent natural categories is a key step toward developing a better understanding of how people learn, form memories, and make decisions. Much research on categorization has focused on artificial categories that are created in the laboratory, since studying natural categories defined on high dimensional stimuli such as images is methodologically challenging. Recent work has produced methods for identifying these representations from observed behavior, such as reverse correlation (RC). We compare RC against an alternative method for inferring the structure of natural categories called Markov chain Monte Carlo with People (MCMCP). Based on an algorithm used in computer science and statistics, MCMCP provides a way to sample from the set of stimuli associated with a natural category. We apply MCMCP and RC to the problem of recovering natural categories that correspond to two kinds of facial affect (happy and sad) from realistic images of faces. Our results show that MCMCP requires fewer trials to obtain a higher quality estimate of people's mental representations of these two categories. PMID- 21972924 TI - Restricted expression of chromatin remodeling associated factor Chd3 during tooth root development. AB - BACKGROUND AND OBJECTIVE: The tooth root is one of the critical parts to maintain tooth function; however, the molecular mechanisms of root development remain unknown. We aimed to identify specific factors for root morphogenesis using a newly developed experimental system. MATERIAL AND METHODS: Tentative cementoblasts and periodontal ligament cells from mouse mandibular molars were isolated using laser capture microdissection. More than 500 cementoblasts and periodontal ligament cells were separately captured. After RNA extraction and amplification, mRNA expression in isolated cementoblasts was compared with that of periodontal ligament cells by cDNA microarray analysis. Then, putative cementoblast-specific genes were subjected to in situ hybridization analysis to confirm the results in mouse mandible. RESULTS: Approximately 2000 genes were differentially expressed between these tissues. Among those genes, zinc finger helicase (ZFH), also termed chromodomain-helicase-DNA-binding protein 3 (Chd3), was one of the highly expressed transcripts in tentative cementoblasts. In situ hybridization revealed that ZFH/Chd3 was strongly expressed in Hertwig's epithelial root sheath rather than in cementum. Moreover, its expression disappeared when root formation was advanced in the first molar. In contrast, Chd3 was continuously expressed in dental epithelial cells of the cervical loop, in which root extension is never terminated. CONCLUSION: These results suggest that ZFH/Chd3 might play an important role in tooth root development and subsequent cementogenesis. PMID- 21972925 TI - Environmental, maternal, and child factors which contribute to early childhood caries: a unifying conceptual model. AB - OBJECTIVES: Although the general pathways connecting the external social environment and child risk factors of early childhood caries (ECC) have been previously identified, the maternal and other links to ECC are not well understood. The aim of this paper is to propose a unifying conceptual model that ties together the broad social environmental, maternal, and child factors that are commonly associated with ECC. METHODS: The aetiological factors of ECC are first reviewed individually to demonstrate their connections with ECC risk followed by presentation of the unifying conceptual model. RESULTS: In severe ECC cases, there is usually a background of social disadvantage associated with low socioeconomic status, ethnicity or immigrant status, and low maternal educational level. These factors are commonly associated with economic and familial stresses which may in turn result in maternal psychological distress. The distress may be compounded by difficult temperaments of the children and can lead to dysfunctional parenting behaviours that place a child at risk for ECC. CONCLUSIONS: The proposed conceptual model provides a framework that connects the social, psychological, and behavioural mediating factors involved in ECC. It demonstrates that the causative pathways involved are best explored using a combination of quantitative and qualitative research. PMID- 21972927 TI - Discussion: psychological factors rather than peripheral fatigue have the final say in limiting aerobic performance. PMID- 21972928 TI - Prognosis of implants and fixed restorations after lateral sinus elevation: a literature review. AB - Aim of this review was to investigate the prognosis of implants inserted in augmented sinuses and fixed restorations supported by these implants. Special attention was given to the impact of grafting material, time of implant placement, residual bone height and type of fixed restoration. An electronic search in PubMed, the German database medpilot and the Cochrane Library was executed followed by supplementary manual search in relevant journals. The search was limited to human studies published up to November 2010. Only publications in English and German, in peer-reviewed journals, were considered. After the initial search and application of selection criteria on titles and abstracts, a full-text analysis of 67 articles was performed, out of which six prospective and three retrospective studies were finally included in the review. The heterogeneous properties of the identified articles did not allow systematic analysis of the data. Success rates of implants were between 96.3% and 100%, survival rates were between 75% and 100%, and survival rates of single crowns, splinted crowns and fixed partial dentures ranged between 96.4% and 100% after a follow-up of 12-101 months. Within the limits of this review, the prognosis of implants and fixed restorations seemed not to be influenced by the type of restorations, graft material, residual bone height and time of implant placement. However, conclusions of this review are based on studies with low level of evidence; therefore, careful interpretation is required. Multicentre randomised controlled clinical trials with sufficient statistical power concentrating on few factors are needed to reach sound conclusions. PMID- 21972929 TI - Surgical treatment of circumflex coronary aneurysm with fistulous connection to coronary sinus associated with persistent left superior vena cava. AB - Circumflex coronary arteriovenous fistula associated with aneurysmal dilatation and draining into coronary sinus (CS) is rare. A 57-year-old female presented with progressive dyspnea and was found to have a tortuous multiloculated aneurysm of the circumflex coronary artery terminating into the CS associated with a persistent left superior vena cava. The operative repair and management of coronary arteriovenous fistula are the subject of this case report and review. PMID- 21972930 TI - Study of acute hemodynamic effects of temporary cardiac resynchronization therapy by Straka et al. PMID- 21972931 TI - Spontaneous formation of wurzite-CdS/zinc blende-CdTe heterodimers through a partial anion exchange reaction. AB - Ion exchange of ionic semiconductor nanoparticles (NPs) is a facile method for the synthesis of type-II semiconductor heterostructured NPs with staggered alignment of band edges for photoelectric applications. Through consideration of the crystallographic orientation and strain at the heterointerface, well-designed heterostructures can be constructed through ion exchange reactions. Here we report the selective synthesis of anisotropically phase-segregated cadmium sulfide (CdS)/ cadmium telluride (CdTe) heterodimers via a novel anion exchange reaction of CdS NPs with an organic telluride precursor. The wurtzite-CdS/zinc blende-CdTe heterodimers in this study resulted from spontaneous phase segregation induced by the differences in the crystal structures of the two phases, accompanying a centrosymmetry breaking of the spherical CdS NPs. The CdS/CdTe heterodimers exhibited photoinduced spatial charge separation because of their staggered band-edge alignment. PMID- 21972932 TI - Accurate prediction of binding thermodynamics for DNA on surfaces. AB - For DNA mounted on surfaces for microarrays, microbeads, and nanoparticles, the nature of the random attachment of oligonucleotide probes to an amorphous surface gives rise to a locally inhomogeneous probe density. These fluctuations of the probe surface density are inherent to all common surface or bead platforms, regardless of whether they exploit either an attachment of presynthesized probes or probes synthesized in situ on the surface. Here, we demonstrate for the first time the crucial role of the probe surface density fluctuations in the performance of DNA arrays. We account for the density fluctuations with a disordered two-dimensional surface model and derive the corresponding array hybridization isotherm that includes a counterion screened electrostatic repulsion between the assayed DNA and probe array. The calculated melting curves are in excellent agreement with published experimental results for arrays with both presynthesized and in situ synthesized oligonucleotide probes. The approach developed allows one to accurately predict the melting curves of DNA arrays using only the known sequence-dependent hybridization enthalpy and entropy in solution and the experimental macroscopic surface density of probes. This opens the way to high-precision theoretical design and optimization of probes and primers in widely used DNA array-based high-throughput technologies for gene expression, genotyping, next-generation sequencing, and surface polymerase extension. PMID- 21972933 TI - Intron retention regulates the expression of pectin methyl esterase inhibitor (Pmei) genes during wheat growth and development. AB - Pectin is an important component of the plant cell wall and its remodelling occurs during normal plant growth or following stress responses. Pectin is secreted into the cell wall in a highly methyl-esterified form and subsequently de-methyl-esterified by pectin methyl esterase (PME), whose activity is controlled by the pectin methyl esterase inhibitor protein (PMEI). Cereal cell wall contains a low amount of pectin; nonetheless the level and pattern of pectin methyl esterification play a primary role during development or pathogen infection. Since few data are available on the role of PMEI in plant development and defence of cereal species, we isolated and characterised three Pmei genes (Tdpmei2.1, Tdpmei2.2 and Tdpmei3) and their encoded products in wheat. Sequence comparisons showed a low level of intra- and inter-specific sequence conservation of PMEIs. Tdpmei2.1 and Tdpmei2.2 share 94% identity at protein level, but only 20% identity with the product of Tdpmei3. All three Tdpmei genes code for functional inhibitors of plant PMEs and do not inhibit microbial PMEs or a plant invertase. RT-PCR analyses demonstrated, for the first time to our knowledge, that Pmei genes are regulated by intron retention. Processed and unprocessed transcripts of Tdpmei2.1 and Tdpmei2.2 accumulated in several organs, but anthers contained only mature transcripts. Tdpmei3 lacks introns and its transcript accumulated mainly in stem internodes. These findings suggest that products encoded by these Tdpmei genes control organ- or tissue-specific activity of specific PME isoforms in wheat. PMID- 21972934 TI - Phenotypic plasticity to light of two congeneric trees from contrasting habitats: Brazilian Atlantic Forest versus cerrado (savanna). AB - The Brazilian Atlantic Forest is a typically multi-layer tropical forest, while cerrado (savanna) is a patchy habitat with different physiognomy. Despite these differences, both habitats have high light heterogeneity. Functional traits of Dalbergia nigra and D. miscolobium from the Atlantic Forest and cerrado, respectively, were evaluated under shade (25% of full sunlight) and full sunlight in a nursery experiment. We hypothesised that both species should benefit from high phenotypic plasticity in relation to light. Plasticity was estimated using the relative distance phenotypic index (RDPI). D. miscolobium had lower shoot growth under both light conditions, suggesting it has low competitive capacity in the forest environment, which could explain its limited ability to expand over areas of Atlantic Forest. The studied species exhibited photoprotection strategies under high light and improved light capture under low light. Stomatal conductance, ETR(max) (maximum electron transport rate), PPFD(sat) (saturating photosynthetically active photon flux density), chlorophyll and carotenoid content had higher RDPI than stem morphological traits. Although both species showed considerable phenotypic plasticity, D. miscolobium had higher RDPI for eight of 11 evaluated traits. This high plasticity could be one of the factors that explain the occurrence of this species in a wide range of environmental conditions, from open grassland to dense woodlands, and it could also reflect its adaptation to high light. D. nigra also had considerable plasticity and good growth performance in both shade and full sunlight, but its absence in areas of cerrado suggests that factors other than light limit its occurrence in these habitats. PMID- 21972935 TI - Microcirculation on a large scale: techniques, tactics and relevance of studying the microcirculation in larger population samples. AB - The role of microcirculatory dysfunction is increasingly being recognized in the etiopathogenesis of cardiovascular disease. Whilst the importance of detailed mechanistic studies to determine the exact nature of these disturbances is without question, it was large-scale population-based studies that first identified the associations between deranged microvascular perfusion, autoregulation or structure, and subsequent target organ damage. This is the subject of considerable studies to establish whether there is a causal effect in either direction, or simply represents shared risk factors, although it is most likely to be a complex combination of bidirectional interactions. The techniques for investigating microcirculatory function have evolved almost exponentially over the last 75 years: So too have the strategies for investigation. Current epidemiological studies are focusing on attempting to untangle the inter relationship between risk factors and pathological mechanisms to attempt to determine whether these represent therapeutic targets or simple markers of unmeasured risk. We plan to review the techniques used for these population-based studies, the advances made, and the clinical implications derived. PMID- 21972936 TI - Anti-inflammatory effects and the underlying mechanisms of action of daidzein in murine macrophages stimulated with Prevotella intermedia lipopolysaccharide. AB - BACKGROUND AND OBJECTIVE: Host modulatory agents directed at inhibiting specific proinflammatory mediators could be beneficial in terms of attenuating periodontal disease progression and potentially enhancing therapeutic responses. The aim of this study was to investigate whether daidzein could modulate the production inflammatory mediators in macrophages stimulated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in periodontal disease, and to delineate underlying mechanisms of action. MATERIAL AND METHODS: LPS was extracted from P. intermedia ATCC 25611 cells by the standard hot phenol-water method. The amounts of nitric oxide (NO) and interleukin-6 (IL-6) secreted into the culture medium were assayed. A real-time PCR was performed to quantify inducible nitric oxide synthase (iNOS) and IL-6 mRNA expression. We used immunoblot analysis to characterize iNOS protein expression, phosphrylation of c Jun N-terminal kinase (JNK) and p38, degradation of inhibitory kappaB-alpha (IkappaB-alpha), nuclear translocation of nuclear factor-kappaB (NF-kappaB) subunits and phosphorylation of signal transducer and activator of transcription 1 (STAT1). The DNA-binding activity of NF-kappaB was assessed by using ELISA based kits. RESULTS: Daidzein significantly inhibited the production of NO and IL 6, as well as their mRNA expression, in P. intermedia LPS-treated RAW264.7 cells. The JNK and p38 pathways were not involved in the regulation of LPS-induced NO and IL-6 release by daidzein. Daidzein inhibited the degradation of IkappaB-alpha induced by P. intermedia LPS. In addition, daidzein suppressed NF-kappaB transcriptional activity via regulation of the nuclear translocation and DNA binding activity of NF-kappaB p50 subunit and blocked STAT1 phosphorylation. CONCLUSION: Although additional studies are required to dissect the molecular mechanism of action, our results suggest that daidzein could be a promising agent for treating inflammatory periodontal disease. Further research in animal models of periodontitis is necessary to better evaluate the potential of daidzein as a novel therapeutic agent to treat periodontal disease. PMID- 21972937 TI - A mass cyanide poisoning from pickling bamboo shoots. AB - CONTEXT: Bamboo shoots contain cyanogenic glycosides named taxiphyllin. Cyanide poisoning from cyanogenic glycosides commonly occurs following ingestion. However, toxicity caused by inhalation of hydrogen cyanide gas (HCN) produced from pickled shoots has never been reported. OBJECTIVE: To describe cyanide poisoning in eight victims who were exposed to HCN produced in a well containing pickling bamboo shoots. MATERIALS AND METHODS: Due to a series of botched rescue attempts, a total of eight patients entered into a 27 m(3) well containing pickled bamboo shoots and immediately lost consciousness. After rescue, two patients developed cardiac arrest, metabolic acidosis and died. Four other patients suffered metabolic acidosis, but recovered after supportive care. The remaining two regained consciousness and recovered soon after the event. Ambient air study and cyanide content of bamboo shoots helped confirm the diagnosis. RESULTS: All patients had high anion gap metabolic acidosis with normal oxygenation. Blood cyanide levels ranged from 2.66 to 3.30 mcg/ml (taken after about 18 h of incident). Ambient air study (21 h after incident) revealed oxygen 20.9%, and sulfur dioxide 19.4 ppm. The instrument was unfortunately not equipped to detect HCN. A simulation study revealed HCN and sulfur dioxide in the ambient air at 10 ppm and 7.5 ppm, respectively. Cyanide content in the bamboo shoots ranged from 39 to 434 mg/kg in the wet shoots. DISCUSSION: This series of patients developed sudden onset of alteration of consciousness and metabolic acidosis upon exposure, and cyanide was confirmed in all victims. The simulation study confirmed the presence of HCN in the ambient air of the well containing bamboo shoots. CONCLUSION: We have reported mass acute cyanide poisoning with two fatalities. The source of HCN was unusual as it was produced from pickling bamboo shoot. PMID- 21972938 TI - Infrared nanoscopy of dirac plasmons at the graphene-SiO2 interface. AB - We report on infrared (IR) nanoscopy of 2D plasmon excitations of Dirac fermions in graphene. This is achieved by confining mid-IR radiation at the apex of a nanoscale tip: an approach yielding 2 orders of magnitude increase in the value of in-plane component of incident wavevector q compared to free space propagation. At these high wavevectors, the Dirac plasmon is found to dramatically enhance the near-field interaction with mid-IR surface phonons of SiO(2) substrate. Our data augmented by detailed modeling establish graphene as a new medium supporting plasmonic effects that can be controlled by gate voltage. PMID- 21972940 TI - Teaching of the repair of defective composite restorations in Scandinavian dental schools. AB - Given increased tooth retention into later years of life, dentists face increasing challenges in maintaining teeth with extensive composite restorations. Accompanying the increase in placement of composite restorations in general practice, there has also been increased evidence that repair, rather than replacement, of composite restorations is being increasingly considered as a treatment option. Previous work has demonstrated that such techniques are often underutilised in practice. The aim of this study was to examine contemporary teaching of composite repair techniques in Scandinavian dental schools. A questionnaire was distributed by email to each of the 12 Scandinavian dental schools in late 2010/early 2011. This questionnaire sought information on the undergraduate teaching of composite repair techniques as well as indications and materials utilised for this technique. A 100% response rate was achieved (12 schools). Eleven of the 12 respondent schools indicated that they included the teaching of composite repair techniques within their dental school programme. The most commonly reported indications for the teaching of the repair of direct composite restorations were tooth substance preservation (11 schools) and reduced risk of harmful effects on the pulp (10 schools). The most commonly taught surface treatment was mechanical roughening of the existing composite restoration, including the removal of the surface layer of material, prior to application of fresh composite (11 schools). Overall, the results of this study showed that the teaching of composite repair techniques is established within Scandinavian dental schools. This may influence the practising habits of dentists graduating from these schools when considering treatment options for defective composite restorations. PMID- 21972941 TI - Extra credit is "old school"--not! PMID- 21972943 TI - A content analysis of advertisements related to oral health in children's Tamil television channels--a preliminary report. AB - AIMS: This study was conducted to examine the nature, content, and duration of advertisements broadcasted during children's Tamil television channels and to determine the extent to which television advertising changes during school holiday and non-holiday periods and between prime time and non-prime time broadcast. METHODS: Television broadcasts on two main children's Tamil television channels were video-recorded over 16 days between 17.00-19.00 hours (non-prime time) and 19.00-21.00 hours (prime time). For each commercial, the type of product advertised, as well as the duration (in seconds), was recorded. Advertisements were categorized as 'food' and 'non-food'. The former category was further subdivided into 'sugar-rich foods' and 'other foods'. The sugar-rich foods were further categorized as liquid, solid and sticky, and slowly dissolving sugars. Commercials related to the promotion of oral health products and non-food products were also recorded. RESULTS: Among the total of 128 h of television programmes recorded, advertising accounted for 10.15% (13.01 hours). The advertisement of sugar-rich food products, non-food and oral hygiene products occupied 50.36%, 38.41% and 1.90%, respectively, of the total advertising time. Solid and sticky products made up 100% of advertisements in this category on Chithiram television channel, compared with 62.5% of advertisements on Chutti television channel. CONCLUSION: It was concluded that the advertising of sugar rich foods, particularly solid and sticky food products, was broadcasted more in Chithiram television channel, during school holidays and during prime time. PMID- 21972944 TI - Inhibition of autophagy may suppress the development of hepatoblastoma. AB - Hepatoblastoma (HB) is a rare cancer but represents the most common liver malignancy in children under 3 years of age. Nevertheless, a clear understanding of the pathogenesis is lacking. Although the treatment of HB has been dramatically improved by combining chemotherapy regimens with surgery, its fatal outcome of fast development and recurrence makes new treatment strategies for HB, based on an improved understanding of the pathogenesis, essential. Autophagy is believed to be important in the progression of cancers. However, the role of autophagy in HB remains to be elucidated. Here, we show that autophagy is activated in HB tissues and cells under the conditions of starvation or chemotherapy, coupled with the over-expression of autophagic-related genes BECN1 and ATG5. Suppression of autophagy with pharmacological agents and small interfering RNAs significantly increased cell apoptosis and retarded proliferation in response to nutrition deprivation and treatment with chemotherapeutics. Our data demonstrate that the BECN1 and ATG5-dependent phosphoinositide 3-kinase (PI3K) signaling pathway is essential for the survival of HB cells and their tolerance to chemotherapy and starvation-induced death, and suggests that modifying such autophagic genes may suppress the development of HB, thus offering a therapeutic potential for patients with HB. PMID- 21972946 TI - The impact of antiproteinuric therapy on the prothrombotic state in patients with overt proteinuria. AB - BACKGROUND: Overt proteinuria is a strong risk factor for thromboembolism, owing to changes in the levels of various coagulation proteins and urinary antithrombin loss. The described coagulation disturbances in these patients are based on outdated studies conducted primarily in the 1970s and 1980s. Whether these coagulation disturbances resolve with antiproteinuric therapy has yet to be studied. METHODS: A total of 32 patients with overt proteinuria (median, 3.7 g day(-1) ; interquartile range, 1.5-5.6) were enrolled in this intervention crossover trial designed to assess optimal antiproteinuric therapy with sodium restriction, losartan, and diuretics. Levels of various procoagulant and anticoagulant proteins, and parameters of two thrombin generation assays (calibrated automated thrombogram [CAT] and prothrombin fragment 1 + 2) were compared between the placebo period and the maximum antiproteinuric treatment period. As a secondary analysis, coagulation measurements of the placebo period in these patients were compared with those of 32 age-matched and sex-matched healthy controls. RESULTS: Median proteinuria was significantly lower during the maximum treatment period (median, 0.9 g day(-1) ; interquartile range, 0.6-1.4; P < 0.001) than during the placebo period. Similarly, levels of various liver synthesized procoagulant and anticoagulant proteins, activated protein C resistance and prothrombin fragment 1 + 2 levels were significantly lower during the maximum treatment period than during the placebo period. However, von Willebrand factor and factor VIII levels were similar. On the basis of the higher levels of procoagulant proteins (fibrinogen, FV, FVIII, and von Willebrand factor) and both thrombin generation assays, patients were substantially more prothrombotic than healthy controls (P < 0.004). CONCLUSIONS: Antiproteinuric therapy ameliorates the prothrombotic state. Proteinuric patients are in a more prothrombotic state than healthy controls. PMID- 21972947 TI - Single channel ICD noise without loss of conductor circuit integrity. PMID- 21972945 TI - Deoxyguanosine forms a bis-adduct with E,E-muconaldehyde, an oxidative metabolite of benzene: implications for the carcinogenicity of benzene. AB - Benzene is employed in large quantities in the chemical industry and is an ubiquitous contaminant in the environment. There is strong epidemiological evidence that benzene exposure induces hematopoietic malignancies, especially acute myeloid leukemia, in humans, but the chemical mechanisms remain obscure. E,E-Muconaldehyde is one of the products of metabolic oxidation of benzene. This paper explores the proposition that E,E-muconaldehyde is capable of forming Gua Gua cross-links. If formed in DNA, the replication and repair of such cross-links might introduce structural defects that could be the origin of the carcinogenicity. We have investigated the reaction of E,E-muconaldehyde with dGuo and found that the reaction yields two pairs of interconverting diastereomers of a novel heptacyclic bis-adduct having a spiro ring system linking the two Gua residues. The structures of the four diastereomers have been established by NMR spectroscopy and their absolute configurations by comparison of CD spectra with those of model compounds having known configurations. The final two steps in the formation of the bis-nucleoside (5-ring -> 6-ring -> 7-ring) have significant reversibility, which is the basis for the observed epimerization. The 6-ring precursor was trapped from the equilibrating mixture by reduction with NaBH(4). The anti relationship of the two Gua residues in the heptacyclic bis-adduct precludes it from being formed in B DNA, but the 6-ring precursor could readily be accommodated as an interchain or intrachain cross-link. It should be possible to form similar cross-links of dCyt, dAdo, the epsilon-amino group of lysine, the imidazole NH of histidine, and N termini of peptides with the dGuo-muconaldehyde monoadduct. PMID- 21972951 TI - Floral ontogeny of Ruteae (Rutaceae) and its systematic implications. AB - Floral development was investigated in Ruta graveolens and Psilopeganum sinense, representing two genera in the tribe Ruteae. Special attention was paid to the sequence of initiation of organ whorls in the androecium and gynoecium. The antepetalous stamens arise at the same level as the antesepalous stamens in both species. The carpels are antepetalous in both taxa, indicating the androecium in both genera is obdiplostemonous. Compared with floral ontogeny of the ancestral genus Phellodendron (Toddalioideae), the obdiplostemonous androecium is a derived condition. The floral apex in P. sinense is quadrangular before initiation of the two carpels. Additionally, there are four dorsal and four ventral traces in the ovary. Integrated morphological and anatomical evidence indicates that the bicarpellate gynoecium in Psilopeganum most likely evolved from a tetracarpellate ancestor. Considering the similarities in morphological, geographical and chromosomal features, the ancestor may be Ruta-like. Further molecular phylogenetic and genetic studies are needed to verify this assumption. PMID- 21972952 TI - Decelerated water dynamics and vibrational couplings of hydrated DNA mapped by two-dimensional infrared spectroscopy. AB - Double-stranded DNA oligomers containing 23 alternating adenine-thymine base pairs are studied at different hydration levels by femtosecond two-dimensional (2D) infrared spectrosopy. Coupled NH stretching modes of the A-T pairs and OH stretching excitations of the water shell are discerned in the 2D spectra. Limited changes of NH stretching frequencies and line shapes with increasing hydration suggest spectral dynamics governed by DNA rather than water fluctuations. In contrast, OH stretching excitations of the water shell around fully hydrated DNA undergo spectral diffusion on a ~500 fs time scale. The center line slopes of the 2D spectra of hydrated DNA demonstrate a slower decay of the frequency-time correlation function (TCF) than that in neat water, as is evident from a comparison with 2D spectra of neat H(2)O and theoretical TCFs. We attribute this behavior to reduced structural fluctuations of the water shell and a reduced rate of resonant OH stretching energy transfer. PMID- 21972953 TI - Successful treatment of metastatic extramammary Paget's disease with S-1 and docetaxel combination chemotherapy. PMID- 21972954 TI - Basal cell carcinoma of the finger: report of a case. PMID- 21972955 TI - Skin ulcer mimicking pyoderma gangrenosum in a patient with incontinentia pigmenti. PMID- 21972956 TI - Vegetative reproduction capacities of floodplain willows--cutting response to competition and biomass loss. AB - While several studies on regeneration in Salicaceae have focused on seedling recruitment, little is known about factors controlling their vegetative reproduction. In two greenhouse experiments, we studied the response of floodplain willows (Salix fragilis, S. viminalis, S. triandra) to competition with Poa trivialis, and to shoot and root removal when planted as vegetative cuttings. In the first experiment, growth performance variables were analysed in relation to full competition, shoot competition, root competition and control, taking into account two different water levels. After 9 weeks, shoots were removed and the resprouting capacity of the bare cuttings was recorded. In the second experiment, the cutting performance of the three floodplain and an additional two fen willow species (S. cinerea, S. aurita) was compared when grown in three different soil compositions and with two different water levels. After 9 weeks, shoot and root biomass was removed and the bare cuttings were replanted to test their ability to resprout. Cutting performance and secondary resprouting were negatively affected by full and shoot competition while root competition had no or weak effects. The floodplain species performed better than the fen species in all soil types and water levels. Secondary resprouting capacity was also higher in the floodplain species, which showed an additional strong positive response to the previous waterlogging treatment. The results contribute to understanding of the vegetative regeneration ecology of floodplain willows, and suggest that the use of vegetative plantings in restoration plantings could be an effective strategy for recovering floodplain forests. PMID- 21972958 TI - Effects of phosphorus availability and genetic variation of leaf terpene content and emission rate in Pinus pinaster seedlings susceptible and resistant to the pine weevil, Hylobius abietis. AB - We studied the effects of phosphorus fertilisation on foliar terpene concentrations and foliar volatile terpene emission rates in six half-sib families of Pinus pinaster Ait. seedlings. Half of the seedlings were resistant to attack of the pine weevil Hylobius abietis L., a generalist phloem feeder, and the remaining seedlings were susceptible to this insect. We hypothesised that P stress could modify the terpene concentration in the needles and thus lead to altered terpene emission patterns relevant to plant-insect signalling. The total concentration and emission rate ranged between 5732 and 13,995 MUg.g(-1) DW and between 2 and 22 MUg.g(-1) DW.h(-1), respectively. Storage and emission were dominated by the isomers alpha- and beta-pinene (77.2% and 84.2% of the total terpene amount amassed and released, respectively). In both resistant and susceptible families, P stress caused an increase of 31% in foliar terpene concentration with an associated 5-fold decrease in terpene emission rates. A higher terpene content in the leaves implies that the 'excess carbon', available under limiting growth conditions (P scarcity), is allocated to terpene production. Sensitive families showed a greater increase in terpene emission rates with increasing P concentrations, which could explain their susceptibility to H. abietis. PMID- 21972959 TI - Is body mass index a risk factor for isolated off-pump coronary revascularization? AB - OBJECTIVE: The influence of body mass index (BMI) as a risk factor for isolated off-pump coronary artery bypass (OPCAB) surgery is unknown. We postulated that BMI >= 30 kg/m(2) would adversely affect outcomes following OPCAB at our institution. METHODS: From 2002 to 2009, we selected 742 patients (primary, N = 709 [95.6%], re-operative, N = 33 [4.45%]) who underwent isolated OPCAB for analysis. Patients were stratified into groups by BMI: non-obese (BMI < 30 kg/m(2) ) and obese (BMI >= 30 kg/m(2)). Preoperative risk, operative characteristics, and postoperative outcomes were analyzed. Risk-adjusted models evaluated the occurrence of any complication and mortality. RESULTS: Overall crude mortality was 1.5% (11/742). When compared to non-obese (26.12 +/- 2.72 kg/m(2)) recipients, the obese (35.81 +/- 5.69 kg/m(2)) comprised younger patients (62.46 +/- 9.96 years, p < 0.001). Number of diseased vessels, Left ventricular ejection fraction, and baseline renal function was equivalent across groups. Diabetes (53.24%) and hypertension (90.59%) were more prevalent among obese patients (p < 0.001, respectively). Internal mammary artery utilization (p = 0.47), endoscopic vein harvest (p = 0.74), and intra-aortic balloon pump use (p = 0.58) were similar between groups. Interestingly, postoperative blood product requirement was lower in obese versus non-obese recipients (47.35% vs. 56.72%, p < 0.01). Furthermore, intensive care unit stay (p = 0.93), mortality (p = 0.56), and discharge to home (p = 0.09) remained equivalent between groups. Importantly, multivariable logistic regression did not identify BMI >= 30 kg/m(2) as an independent predictor of any complication (p = 0.21) or mortality (p = 0.74). CONCLUSIONS: Obesity does not influence operative characteristics or effect outcomes after OPCAB. BMI >= 30 kg/m(2) should not be considered a prohibitive risk factor in isolated off-pump coronary revascularization. PMID- 21972957 TI - MRI analysis in temporal lobe epilepsy: cortical thinning and white matter disruptions are related to side of seizure onset. AB - PURPOSE: Past studies reported more widespread structural brain abnormalities in patients with left compared to right temporal lobe epilepsy (TLE), but the profile of these differences remains unknown. This study investigated the relationship between cortical thinning, white matter compromise, epilepsy variables, and the side of seizure onset, in patients with TLE. METHODS: We performed diffusion tensor imaging tractography and cortical thickness analyses of 18 patients with left TLE (LTLE), 18 patients with right TLE (RTLE), and 36 controls. We investigated the relationship among brain structural abnormalities, side of seizure onset, age of seizure onset, and disease duration. KEY FINDINGS: Patients with TLE displayed cortical thinning and white matter compromise, predominately on the side ipsilateral to the seizure onset. Relative to RTLE, patients with LTLE showed more widespread abnormalities, particularly in white matter fiber tracts. Greater compromise in white matter integrity was associated with earlier age of seizure onset, whereas cortical thinning was marginally associated with disease duration. SIGNIFICANCE: These data support previous findings of LTLE showing greater structural compromise than RTLE, and suggest that mechanisms may not be uniform for gray and white matter compromise in patients with LTLE and RTLE. These results may indicate that LTLE is different from RTLE, possibly due to greater vulnerability of the left hemisphere to early injury and the progressive effects of seizures. PMID- 21972960 TI - A study of the population of Paraguay through isonymy. AB - In order to describe the isonymic structure of Paraguay, the distribution of 4,843,868 surnames of 2,882,163 persons was studied in the 18 departments and 237 districts of the nation. The correlations between isonymic and geographic distances for departments were r = 0.713 +/- 0.052 for Euclidean distance, 0.597 +/- 0.074 for Nei's and 0.582 +/- 0.076 for Lasker's, and for districts r = 0.320 +/- 0.007, 0.235 +/- 0.009 and 0.422 +/- 0.008, respectively. Average alpha was 151 for the entire country, 140.6 +/- 6.5 for departments and 108.2 +/- 2.7 for districts. The geographical distribution of districts'alpha is compatible with the settlement of subsequent groups of migrants moving from South towards the Centre and North of Paraguay. The geographical analysis of the first three components of Lasker's isonymy distance matrix is in agreement with such a process. The prevalence of Spanish-Amerindian ethnic groups and the relative absence of indigenous surnames (absence due mainly to the forced surname change of 1848) is in agreement with the diffusion of Spanish speaking males over a low density area populated by indigenous groups. The present distribution of Y markers and mt-markers in the available studies in most Latin American populations is compatible with this process. PMID- 21972961 TI - Chromosome-wide haplotype sharing: a measure integrating recombination information to reconstruct the phylogeny of human populations. AB - The vast amount of recombination information in the human genome has long been ignored or deliberately avoided in studies on human population genetic relationships. One reason is that estimation of the recombination parameter from genotyping data is computationally challenging and practically difficult. Here we propose chromosome-wide haplotype sharing (CHS) as a measure of genetic similarity between human populations, which is an indirect approach to integrate recombination information. We showed in both empirical and simulated data that recombination differences and genetic differences between human populations are strongly correlated, indicating that recombination events in different human populations are evolutionarily related. We further demonstrated that CHS can be used to reconstruct reliable phylogenies of human populations and the majority of the variation in CHS matrix can be attributed to recombination. However, for distantly related populations, the utility of CHS to reconstruct correct phylogeny is limited, suggesting that the linear correlation of CHS and population divergence could have been disturbed by recurrent recombination events over a large time scale. The CHS we proposed in this study is a practical approach without involving computationally challenging and time-consuming estimation of recombination parameter. The advantage of CHS is rooted in its integration of both drift and recombination information, therefore providing additional resolution especially for populations separated recently. PMID- 21972962 TI - Analysis of potential genomic confounding in genetic association studies and an online genomic confounding browser (GCB). AB - Genome-wide association studies have transformed genetic studies of disease susceptibility, identifying many variants that may tag functional polymorphism nearby. Variants are often ascribed to a physically close gene exhibiting plausible functionality for a causal pathway. However, more physically remote genes may be at a lesser linkage or linkage disequilibrium (LD) distance from the tested SNP and could therefore contain the functional variant tagged. This analysis aims to identify instances where research may be misled by misassociation of a variant with a gene and develop tools to analyse genomic confounding. A catalogue of reported associations was systematically analysed for unreported genes which may represent the true functionality ascribed to a reported variant, calculating physical and genetic distances for all genes within 1 cM of the tagging polymorphism. Results revealed 55 SNPs where recombination was lower between the identified SNP and a physically more remote gene than initially reported, and 374 where an alternative gene was genetically and physically closer than the reported gene. Analyses show potential for genomic confounding through false inferences of variant association to a gene. An online visualization tool (http://gcb.genes.org.uk/) was developed to plot genes by physical and genetic distance relative to a variant, along with LD data. PMID- 21972963 TI - Testing for Hardy Weinberg Equilibrium in national household surveys that collect family-based genetic data. AB - In population-based household surveys, for example, the National Health and Nutrition Examination Survey (NHANES), blood-related individuals are often sampled from the same household. Therefore, genetic data collected from national household surveys are often correlated due to two levels of clustering (correlation) with one induced by the multistage geographical cluster sampling, and the other induced by biological inheritance among multiple participants within the same sampled household. In this paper, we develop efficient statistical methods that consider the weighting effect induced by the differential selection probabilities in complex sample designs, as well as the clustering (correlation) effects described above. We examine and compare the magnitude of each level of clustering effects under different scenarios and identify the scenario under which the clustering effect induced by one level dominates the other. The proposed method is evaluated via Monte Carlo simulation studies and illustrated using the Hispanic Health and Nutrition Survey (HHANES) with simulated genotype data. PMID- 21972964 TI - A novel method to detect gene-gene interactions in structured populations: MDR SP. AB - Complex diseases are presumed to be the result of multiple genes and environmental factors, which emphasize the importance of gene - gene and gene - environment interactions. Traditional parametric approaches are limited in their ability to detect high-order interactions and handle sparse data, and standard stepwise procedures may miss interactions with undetectable main effects. To address these limitations, the multifactor dimensionality reduction (MDR) method was developed. MDR is well suited for examining high-order interactions and detecting interactions without main effects. Like most statistical methods in genetic association studies, MDR may also lead to a false positive in the presence of population stratification. Although many statistical methods have been proposed to detect main effects and control for population stratification using genomic markers, not many methods are available to detect interactions and control for population stratification at the same time. In this article, we developed a novel test, MDR in structured populations (MDR-SP), to detect the interactions and control for population stratification. MDR-SP is applicable to both quantitative and qualitative traits and can incorporate covariates. We present simulation studies to demonstrate the validity of the test and to evaluate its power. PMID- 21972965 TI - Toward total automation of microfluidics for extraterrestial in situ analysis. AB - Despite multiple orbiter and landed missions to extraterrestrial bodies in the solar system, including Mars and Titan, we still know relatively little about the detailed chemical composition and quantity of organics and biomolecules in those bodies. For chemical analysis on astrobiologically relevant targets such as Mars, Europa, Titan, and Enceladus, instrumentation should be extremely sensitive and capable of analyzing a broad range of organic molecules. Microchip capillary electrophoresis (MUCE) with laser-induced fluorescence (LIF) detection provides this required sensitivity and targets a wide range of relevant markers but, to date, has lacked the necessary degree of automation for spaceflight applications. Here we describe a fully integrated microfluidic device capable of performing automated end-to-end analyses of amino acids by MUCE with LIF detection. The device integrates an array of pneumatically actuated valves and pumps for autonomous fluidic routing with an electrophoretic channel. Operation of the device, including manipulation of liquids for sample pretreatment and electrophoretic analysis, was performed exclusively via computer control. The device was validated by mixing of laboratory standards and labeling of amino acids with Pacific Blue succinimidyl ester followed by electrophoretic analysis. To our knowledge, this is the first demonstration of completely automated end-to end MUCE analyses on a single, fully integrated microfluidic device. PMID- 21972966 TI - Endophytic colonisation of Bacillus subtilis in the roots of Robinia pseudoacacia L. AB - The endophytic colonisation of Bacillus subtilis strain GXJM08, isolated from roots of Podocarpus imbricatus B1. Enum. P1. Jav., in roots of the leguminous plant Robinia pseudoacacia L. was investigated. Ultrastructure observations showed that B. subtilis caused morphological changes in the root hair and colonised the plant through infected root hairs. The structure of the infection thread was similar to that of rhizobia, but the structure of infected cells was different. B. subtilis is also different from rhizobia and plant pathogens in terms of the formation of a peribacteroid membrane and the mode of penetration through the host cell wall. Our results provide a basis for studying development of the mutualistic symbiotic relationship between B. subtilis and plants, and a basis for studying the mechanism of the B. subtilis-plant interaction. PMID- 21972967 TI - A small nonrule of 3 compatible fragment library provides high hit rate of endothiapepsin crystal structures with various fragment chemotypes. AB - Druglike molecules are defined by Lipinski's rule of 5, to characterize fragment thresholds, they have been reduced from 5 to 3 (Astex's rule of 3). They are applied to assemble fragment libraries, and providers use them to select fragments for commercial offer. We question whether these rules are too stringent to compose fragment libraries with candidates exhibiting sufficient room for chemical subsequent growing and merging modifications as appropriate functional groups for chemical transformations are required. Usually these groups exhibit properties as hydrogen bond donors/acceptors and provide entry points for optimization chemistry. We therefore designed a fragment library (364 entries) without strictly applying the rule of 3. For initial screening for endothiapepsin binding, we performed a biochemical cleavage assay of a fluorogenic substrate at 1 mM. "Hits" were defined to inhibit the enzyme by at least 40%. Fifty-five hits were suggested and subsequently soaked into endothiapepsin crystals. Eleven crystal structures could be determined covering fragments with diverse binding modes: (i) direct binding to the catalytic dyad aspartates, (ii) water-mediated binding to the aspartates, (iii) no direct interaction with the dyad. They occupy different specificity pockets. Only 4 of the 11 fragments are consistent with the rule of 3. Restriction to this rule would have limited the fragment hits to a strongly reduced variety of chemotypes. PMID- 21972968 TI - Green power--a modest experiment. PMID- 21972970 TI - Pathophysiology, staging and therapy of severe sepsis in baboon models. AB - We review our baboon models of Escherichia coli sepsis that mimic, respectively, the shock/disseminated intravascular coagulation (DIC) and organ failure variants of severe sepsis, and analyse the pathophysiologic processes that are unique to each. The multi-stage, multi-factorial characteristics of severe sepsis develop as a result of the initial insult, which - depending on its intensity - activates components of the intravascular compartment leading to overwhelming shock/DIC; or initiates a sequence of events involving both the intra- and extravascular (tissues) compartments that lead to organ failure. In the latter case, the disorder passes through two stages: an initial inflammatory/coagulopathic intravascular first stage triggered by E. coli, followed by an extravascular second stage, involving components unique to each organ and triggered by ischemia/reperfusion (oxidative stress and histone release). Although a myriad of overlapping cellular and molecular components are involved, it is the context in which these components are brought into play that determine whether shock/DIC or organ failure predominate. For example, inflammatory and thrombotic responses amplified by thrombin in the first case whereas similar responses are amplified by complement activation products in the second. Rather than blocking specific mediators, we found that attenuation of the thrombin and complement amplification pathways can effectively reverse the shock/DIC and organ failure exhibited by the LD(100) and LD(50) E. coli models of severe sepsis, respectively. Translation of these concepts to successful intervention in the respective baboon models of E. coli sepsis and the application to their clinical counterparts is described. PMID- 21972971 TI - Low-dose cyclophosphamide associated with hemorrhagic cystitis in a breast cancer patient. AB - Hemorrhagic cystitis is a known complication of high-dose cyclophosphamide treatment, generally occurring at doses greater than 100 g. There are few reports of hemorrhagic cystitis occurring with low-dose cyclophosphamide therapy, and this complication has not been described in breast cancer patients. We present a case of a patient with stage IIB breast cancer who developed clinical, radiographic, and pathologic evidence of hemorrhagic cystitis after a single 600 mg/m(2) dose of cyclophosphamide. Three subsequent cycles of cyclophosphamide with the addition of IV hydration and MESNA were given without complication, and the patient's urologic symptoms resolved. Repeat cystoscopy demonstrated pathologic resolution of the cystitis. We review the literature regarding proposed mechanisms of hemorrhagic cystitis, and discuss the applicability of these hypotheses in our patient. PMID- 21972972 TI - Highlight: the Winter School on proteinases and their inhibitors. PMID- 21972973 TI - Contribution of cathepsin L to secretome composition and cleavage pattern of mouse embryonic fibroblasts. AB - The endolysosomal cysteine endoprotease cathepsin L is secreted from cells in a variety of pathological conditions such as cancer and arthritis. We compared the secretome composition and extracellular proteolytic cleavage events in cell supernatants of cathepsin L-deficient and wild-type mouse embryonic fibroblasts (MEFs). Quantitative proteomic comparison of cell conditioned media indicated that cathepsin L deficiency affects, albeit in a limited manner, the abundances of extracellular matrix (ECM) components, signaling proteins, and further proteases as well as endogenous protease inhibitors. Immunodetection corroborated that cathepsin L deficiency results in decreased abundance of the ECM protein periostin and elevated abundance of matrix metalloprotease (MMP)-2. While mRNA levels of MMP-2 were not affected by cathepsin L ablation, periostin mRNA levels were reduced, potentially indicating a downstream effect. To characterize cathepsin L contribution to extracellular proteolysis, we performed terminal amine isotopic labeling of substrates (TAILS), an N-terminomic technique for the identification and quantification of native and proteolytically generated protein N-termini. TAILS identified >1500 protein N-termini. Cathepsin L deficiency predominantly reduced the magnitude of collagenous cleavage sites C-terminal to a proline residue. This contradicts cathepsin L active site specificity and indicates altered activity of further proteases as a result of cathepsin L ablation. PMID- 21972974 TI - The significance of the C(alpha) substituent in the selective inhibition of matrix metalloproteinases 1 and 9. AB - Matrix metalloproteinases (MMPs) cleave and degrade most components of the extracellular matrix, and unregulated MMP activity has been correlated to cancer and metastasis. Hence there is a burgeoning need to develop inhibitors that bind selectively to structurally similar MMPs. The inhibition profiles of peptidomimetics containing C(alpha) substituents at the alpha,beta unsaturated carbon were evaluated against the recombinant forms of ADAM17, MMP1, and MMP9. The dicarboxylic acid D2 and hydroxamate C2 inhibited MMP9 but not MMP1. The unsaturated compound E2 displayed selective inhibition for MMP1, compared with the saturated precursor C2, with an IC(50) value of 3.91 MUm. The molecular basis for this selectivity was further investigated by the molecular docking of E2 and D2 into the active sites of MMP1 and MMP9. These data demonstrate hydrogen bonding interactions between the carbonyl group of the C(alpha) substituent of E2 and the side chain of Asn180 present in the active site of MMP1. Conversely, the docked MMP9-D2 structure shows hydrophobic and hydrogen bonding between the ligand's morpholine substituent and second carboxylic acid group with Leu187 and an amide, respectively. This study suggests that substituents other than P(1)' and P(2)' may confer selectivity among MMPs and may aid in the search for novel lead compounds. PMID- 21972976 TI - A new furanocoumarin from the mangrove endophytic fungus Penicillium sp. (ZH16). AB - A new furanocoumarin, 5-methyl-8-(3-methylbut-2-enyl) furanocoumarin (1), together with seven known compounds, sterequinone C (2), cyclo(6,7-en-Pro-L-Phe) (3), bergapten, scopoletin, umbelliferone, 1,7-dihydroxyxanthone and 3,5 dimethoxybiphenyl, was isolated from the mangrove endophytic fungus, Penicillium sp. ZH16 obtained from the South China Sea. Their structures were determined by analysis of spectroscopic data. Compound 1 exhibited cytotoxicity against KB and KB(V)200 cells in vitro with IC(50) values 5 and 10 ug mL(-1), respectively. PMID- 21972975 TI - Stroke mechanism in patients with non-valvular atrial fibrillation according to the CHADS2 and CHA2 DS2 -VASc scores. AB - BACKGROUND AND PURPOSE: The CHADS(2) and CHA(2) DS(2) -VASc scores are useful to stratify embolic risks in patients with non-valvular atrial fibrillation (NVAF) and to identify patients eligible for anticoagulation. Although the risk of stoke increases in patients with higher CHADS(2) or CHA(2) DS(2) -VASc scores, it is uncertain why the stroke rate increases in them. Concomitant potential cardiac sources of embolism (PCSE) may be more frequent in patients with higher CHADS(2) or CHA(2) DS(2) -VASc scores because stroke risks increase when concomitant PCSE is present in Atrial fibrillation (AF). On the other hand, atherothrombosis may be the cause when considering that most components of the CHADS(2) and CHA(2) DS(2) -VASc scores are risk factors for atherosclerosis. METHODS: Amongst 5493 stroke patients who were prospectively registered with the stroke registry for 11years, 860 consecutive patients with NVAF were included for this study. We investigated the mechanisms of stroke according to the CHADS(2) /CHA(2) DS(2) VASc score in stroke patients with NVAF. RESULTS: Amongst 860 patients, concomitant PCSE were found in 334 patients (38.8%). The number of PCSE increased as the CHADS(2) /CHA(2) DS(2) -VASc score increased (P<0.001). Of individual PCSE, akinetic left ventricular segment, hypokinetic left ventricular segment and myocardial infarction <4weeks were associated with the CHADS(2) /CHA(2) DS(2) VASc score. The presence of possible atherothrombotic mechanism, in addition to AF, was suggested in 27.3%. The proportion of patients with concomitant presence of possible atherothrombosis was increased as the CHADS(2) /CHA(2) DS(2) -VASc score increased (P<0.001). CONCLUSIONS: Increased frequency of concomitant PCSE and that of the atherothrombotic mechanism may explain the high risk of stroke in patients with higher CHADS(2) /CHA(2) DS(2) -VASc score. PMID- 21972977 TI - Characterization of an oxidoreductase from the arylamine N-acetyltransferase operon in Mycobacterium smegmatis. AB - Mycobacterium tuberculosis, the most successful bacterial pathogen, causes tuberculosis, a disease that still causes more than 2 million deaths per year. Arylamine N-acetyltransferase is an enzyme that is conserved in most Mycobacterium spp. The nat gene belongs to an operon that is important for the intracellular survival of M. tuberculosis within macrophages. The nat operon in Mycobacterium smegmatis and other fast-growing mycobacterial species has a unique organization containing genes with uncharacterized function. Here, we describe the biochemical, biophysical and structural characterization of the MSMEG_0308 gene product (MS0308) of the M. smegmatis nat operon. While characterizing the function of MS0308, we validated the oxidoreductase property; however, we found that the enzyme was not utilizing dihydrofolate as its substrate, hence we first report that MS0308 is not a dihydrofolate reductase, as annotated in the genome. The structure of this oxidoreductase was solved at 2.0 A in complex with the cofactor NADPH and has revealed the hydrophobic pocket where the endogenous substrate binds. PMID- 21972978 TI - Different strategies of Lotus japonicus, L. corniculatus and L. tenuis to deal with complete submergence at seedling stage. AB - Two main strategies allow plants to deal with submergence: (i) escape from below water by means of shoot elongation, or (ii) remaining quiescent under the water until water subsides and then resume growth. We investigated these strategies in seedlings of Lotus japonicus, L. corniculatus and L. tenuis subjected to control and submergence for 12 days, with a subsequent 30-day recovery period. All three species survived submergence but used different strategies. Submerged seedlings of L. japonicus exhibited an escape strategy (emerging from water) as a result of preferential carbon allocation towards shoot mass and lengthening, in detriment to root growth. In contrast, seedlings of L. corniculatus and L. tenuis became quiescent, with no biomass accumulation, no new unfolding of leaves and no shoot elongation. Upon de-submergence, seedlings of L. japonicus had the lowest recovery growth (a biomass and shoot height 58% and 40% less than controls, respectively), L. corniculatus was intermediate and L. tenuis showed the greatest recovery growth. Previously submerged seedlings of L. tenuis did not differ from their controls, either in final shoot biomass or shoot height. Thus, for the studied species, quiescence appears to be an adequate strategy for tolerance of short-term (i.e., 12 days) complete submergence, being consistent with field observations of L. tenuis colonisation of flood-prone environments. PMID- 21972979 TI - Chromosomal stability during ex vivo expansion of UCB CD34(+) cells. AB - OBJECTIVES: Ex vivo expansion is a feasible strategy, which may overcome limitation of the very low frequency of haematopoietic stem/progenitor cells, in umbilical cord blood (UCB). However, both quality of cells and safety of expanded population are critical issues to be addressed for their clinical application. Hence, in this study, we evaluated genetic stability of UCB-derived CD34(+) cells during ex vivo culture, based on karyotype analysis, as well as its effect on cell proliferation characteristics. MATERIALS AND METHODS: CD34(+) cells were isolated from human UCB samples by immunomagnetic separation and were expanded ex vivo over a 28-day period. Expansion of total nucleate cells, CD34(+) cells and CD34(+) CD38(-) cells was investigated. Karyotype analysis of the expanded cells from six randomly selected UCB samples was performed to evaluate their genetic stability. RESULTS: Chromosomal abnormality of expanded cells mainly appeared by day 14, but was seldom sustained until day 28. None of the chromosomal abnormal samples displayed neoplastic proliferation, and expanded cells with altered chromosomes did not show obvious transformation phenomena according to soft agar assay. CONCLUSIONS: Ex vivo expansion could lead to occurrence of chromosomal abnormality, although here it did not produce excessive proliferative advantage of the expended cells. Importantly, chromosomal alteration seemed not to be inheritable and unlikely to result in malignant transformation. However, further in-depth evaluation of potential clinical risks of chromosomal abnormality is warranted. PMID- 21972980 TI - Negative and positive persistent photoconductance in graphene. AB - Persistent photoconductance, a prolonged light-induced conducting behavior that lasts several hundred seconds, has been observed in semiconductors. Here we report persistent negative photoconductance and consecutive prominent persistent positive photoconductance in graphene. Unusually large yields of negative PC (34%) and positive PC (1652%) and remarkably long negative transient response time (several hours) were observed. Such high yields were reduced in multilayer graphene and were quenched under vacuum conditions. Two-dimensional metallic graphene strongly interacts with environment and/or substrate, causing this phenomenon, which is markedly different from that in three-dimensional semiconductors and nanoparticles. PMID- 21972981 TI - Interchangeable effects of gibberellic acid and temperature on embryo growth, seed germination and epicotyl emergence in Ribes multiflorum ssp. sandalioticum (Grossulariaceae). AB - Morphophysiological dormancy was investigated in seeds of Ribes multiflorum Kit ex Roem et Schult. ssp. sandalioticum Arrigoni, a rare mountain species endemic to Sardinia (Italy). There were no differences in imbibition rates between intact and scarified seeds, suggesting a lack of physical dormancy, while methylene blue solution (0.5%) highlighted a preferential pathway for solution entrance through the raphe. Embryos were small at seed dispersal, with an initial embryo:seed ratio (E:S) of ca. 0.2 (embryo length, ca. 0.5 mm), whereas the critical E:S ratio for germination was three times longer (ca. 0.6). Gibberellic acid (GA(3), 250 mg . l(-1)) and warm stratification (25 degrees C for 3 months) followed by low temperature (<15 degrees C) enhanced embryo growth rate (maximum of ca. 0.04 mm . day(-1) at 10 degrees C) and subsequent seed germination (radicle emergence; ca. 80% at 10 degrees C). Low germination occurred at warmer temperatures, and cold stratification (5 degrees C for 3 months) induced secondary dormancy. After radicle emergence, epicotyl emergence was delayed for ca. 2 months for seeds from three different populations. Mean time of epicotyl emergence was affected by GA(3) . Seeds of this species showed non-deep simple (root) - non-deep simple (epicotyl) morphophysiological dormancy, highlighting a high synchronisation with Mediterranean seasonality in all the investigated populations. PMID- 21972982 TI - Difficulties in disengaging attentional resources from self-generated thoughts moderate the link between dysphoria and maladaptive self-referential thinking. AB - Negative emotions increase self-focused attention, a core feature of depression and anxiety-related disorders. However, the cognitive mechanisms associated with the tendency to self-focus-and, conversely, with the ability to voluntarily disengage attentional resources from the self and direct them towards the external environment-remain poorly understood. Thus, this study aimed to examine whether a specific cognitive control mechanism that directs attention between self-generated thoughts and external information might moderate the relationship between dysphoria and maladaptive self-referential thinking. Results showed that dysphoria increases the frequency of rumination, self-blame, and catastrophising, especially for participants who have more difficulty in switching from self generated thoughts to information provided by the environment. These results shed new light on the cognitive mechanisms underlying maladaptive self-referential thinking associated with dysphoria. More specifically, this specific cognitive mechanism might play a key role in the maintenance or amplification of a depressed mood. PMID- 21972983 TI - Patient and cardiologist perceptions on decision making for implantable cardioverter-defibrillators: a qualitative study. AB - BACKGROUND: Although implantable cardioverter-defibrillators (ICDs) reduce mortality in selected patients, they are also associated with potential risks. Periprocedural decision making requires understanding both benefits and risks. METHODS: This qualitative study aims to understand cardiologists' and patients' perspectives about decision making surrounding ICD implantation using semi structured, in-depth interviews. We interviewed 11 cardiologists (including four electrophysiologists) and 20 patients (14 with ICDs; six who declined ICDs). The data were analyzed through the theoretical lens of patient-centered care using the constant comparative method. RESULTS: Cardiologists emphasized the benefits of ICD therapy but varied substantially in the extent to which they emphasized the various risks associated with ICD implantation with patients. Cardiologists indicated that they were influenced by the benefits of therapy as presented in published guidelines. Many patients who chose to receive an ICD indicated that they followed the advice of their physician without questioning the risks and benefits of the device. Some ICD recipients described not learning many of the risks until after device implantation or when they experienced these side effects. Patients who declined ICD implantation were concerned that the ICD was unnecessary or believed that the risks related to sudden death without an ICD did not apply to them. Only one patient considered the trade-off between dying quickly versus living longer with progressive heart failure. CONCLUSIONS: In our sample, cardiologists' desire to adhere to published guidelines appears to inhibit shared decision making. The marked variability in the discussions surrounding ICD decisions highlights a need for an improved process of ICD decision making. PMID- 21972984 TI - Transient hyperammonemia in seizures: a prospective study. AB - PURPOSE: To investigate the incidence and duration of transient hyperammonemia in seizures and to verify the significant confounders related to transient hyperammonemia in seizures. METHODS: One hundred twenty-one noncirrhotic adult patients with seizures admitted to the emergency department were enrolled in the study. Laboratory examination was performed, including plasma ammonia level assessment. In addition, the basic parameters, underlying systemic diseases, and seizure-related conditions were assessed. The patients were classified into a group with hyperammonemia on arrival and a group without, in order to compare seizure-related adverse events that occurred during a 9-month period. KEY FINDINGS: The incidence of hyperammonemia in patients with seizures was 67.77%. Plasma ammonia levels in patients with generalized tonic-clonic (GTC) seizures were significantly higher than those in patients in the non-GTC seizure group (median 174.5 vs. 47 MUg/dl; proportion 76.5% vs. 21.1%; p < 0.001). Median plasma ammonia levels decreased spontaneously from 250 to 54 MUg/dl (p < 0.00001) in an average interval of 466.79 min. GTC seizures (p < 0.0001), male gender (p < 0.0001), bicarbonate (p < 0.0001), diabetes (p = 0.0139), and alcohol-related seizures (p = 0.0002) were significant factors associated with hyperammonemia on arrival. No significant differences related to admission rates or mortalities were found between the two groups. SIGNIFICANCE: The presence of transient hyperammonemia in patients with seizures is significantly related to GTC seizures, male gender, bicarbonate, diabetes, and alcohol-related seizures. The appropriate period to study ammonia levels following a seizure event is within 8 h. Because these phenomena are self-limited, ammonia-lowering management are not necessary. Hyperammonemia on arrival is not necessarily related to adverse outcomes. PMID- 21972985 TI - Left internal thoracic artery composite grafting with the right internal thoracic versus radial artery in coronary artery bypass grafting. AB - BACKGROUND: The aim of this study was to compare the results of all arterial multivessel coronary artery bypass grafting using the left internal thoracic artery composite bypass graft constructed with the right internal thoracic artery or radial artery. METHODS: Patients undergoing coronary artery bypass grafting with a left internal thoracic artery constructed as a composite bypass graft with either a right internal thoracic artery (n = 45; RITA group) or radial artery (n = 352; RA group) between 2003 and 2009 were included in the present study. RESULTS: The three-year patency rates for the RITA and RA groups were 91.8%+/- 4.3% and 78.6%+/- 3.4%, respectively (p = 0.12). Adjustments for covariates revealed the radial artery patency to be significantly inferior to the right internal thoracic artery graft (hazard ratio 4.35, 95% confidence interval 1.05 to 18.0; p = 0.043). Reintervention for target coronary artery occlusion was required in two patients in the RA group over a mean follow-up period of 35.5 +/- 21.5 months. There were 43 deaths in the entire cohort of which 20 were cardiac. After adjustment for significant variables, the risk of all-cause mortality, cardiac death, and the composite of adverse events (death, reintervention, myocardial infarction, and stroke) were similar for the two groups (p = 0.98, 0.99, and 0.21, respectively). CONCLUSIONS: Although superior patency was observed with the right internal thoracic artery over the radial artery graft, a significant commensurate benefit in reducing the incidence of major adverse clinical outcomes was not necessarily shown. PMID- 21972986 TI - Perception of overweight is associated with poor academic performance in US adolescents. AB - BACKGROUND: To improve understanding of the mechanisms affecting the relationship between adolescent obesity and poor academic performance, we examined the association of overweight or perceived weight status with academic achievement. METHODS: We performed a cross-sectional study of 14-17-year-olds (N = 11,012) from the nationally representative 2003 Youth Risk Behavior Survey. The main outcome measure was self-reported grades (mostly A, B, C, D, or F). The primary independent variables were medically defined overweight (body mass index [BMI] >= 85th percentile), obesity (BMI >= 95th percentile), and participants' perception of their weight status. RESULTS: Medically defined overweight youth were less likely to report higher grades in unadjusted analysis (OR 0.67, 95% CI: 0.60 0.76, p < .001) and after adjustment for demographics, depression, television and video game use, and physical activity (OR 0.83, 95% CI: 0.74-0.94, p = .003). Statistically significant results also were seen with medically defined obese participants. Youth who perceived themselves as overweight were less likely to report higher grades (OR 0.82, 95% CI: 0.73-0.92, p = .001) in unadjusted analysis and after adjustment for the same variables (OR 0.79, 95% CI: 0.68-0.91, p = .002). The perception of overweight was a more significant determinant of academic performance (OR 0.81, 95% CI: 0.69-0.95, p = .012) compared to medically defined obesity (OR 0.90, 95% CI: 0.77-1.05, p = .174). CONCLUSIONS: Perceived overweight status is negatively associated with academic performance, regardless of actual weight status. These findings suggest that perception of overweight may be a mechanism for prior results indicating a negative association of obesity and academic achievements, and have implications for the academic health of these adolescents. PMID- 21972987 TI - Alcohol/drug exposure, HIV-related sexual risk among urban American Indian and Alaska Native Youth: evidence from a national survey. AB - BACKGROUND: Migration of the native populations from reservations to the urban areas has resulted in mixed ethnicities of American Indian/Alaskan Native (AIAN) children. Minority youth require special attention and services in urban schools as they disproportionately experience poverty, low educational attainment, unemployment, and single-parent status. METHODS: We used 2005 and 2007 Youth Risk Behavior Survey data to examine alcohol/drug use patterns and their association with sexual risk taking among AIAN only (single-racial) and biracial youth in combination with White, African American, or Hispanic ethnicities (N = 1178). RESULTS: Overall, one half of the students were sexually active, with significantly higher rates among males; AIAN-Black students initiated sex earlier than the other groups. Condom nonuse is higher among AIAN-Whites (>50%) compared to one third of AIAN-Hispanics and one fourth of AIAN-Blacks. Nearly 10% of all students, except AIAN-Blacks, reported lifetime use of heroin/meth. Sexual behavior was significantly associated with episodic drinking. Students with Hispanic background have twice the odds of being sexually active compared to AIANs. CONCLUSIONS: Our findings underscore growing health care needs and targeted prevention initiatives for mixed racial underserved native youth. Urban school settings have potential to deliver services and offer alcohol/drug prevention programs to address the needs of mixed racial native urban youth. Using the School Based Health Clinic model has been successful; we need to reform prevention approaches to accommodate needs of multiracial urban native youth. PMID- 21972988 TI - Promoting uptake of the HPV vaccine: the knowledge and views of school staff. AB - BACKGROUND: School-based human papillomavirus (HPV)/cervical cancer vaccination programs have been implemented widely, but few studies have investigated the knowledge and views of school staff about this new vaccine. METHODS: Prior to the introduction of the HPV vaccine in 2009, we surveyed staff at 14 socioeconomically diverse schools to assess views toward this new program, including staff's information needs, ideas on promoting return of consent forms, and uptake of the vaccine among minority groups. RESULTS: Of 583 invited staff, 456 participated (78%). About 58% of the participants knew about the link between HPV and cervical cancer, and that HPV is passed on during sexual contact. When asked if vaccination would increase sexual activity at a younger age, 71% disagreed, 6% agreed, and 23% were unsure. The majority of staff agreed that vaccine uptake could be improved through provision of information and consent forms in indigenous and Pacific languages; ensuring parents are well informed and girls educated about the vaccine; involving community groups and by extending availability of the vaccine into community settings as well as school and primary care. Three fourths of the staff surveyed wanted more information about the program before and during its implementation. CONCLUSIONS: This important group of stakeholders requires appropriate information so that they can support girls and their parents in deciding whether to have the vaccine. School staff members are potential health advocates with whom consultation should occur before and during the implementation of such programs. PMID- 21972989 TI - The relationship between school multiculturalism and interpersonal violence: an exploratory study. AB - BACKGROUND: Multiculturalism has been purported to be supportive of positive youth development and outcomes. This study examined the relationship between perceived school multiculturalism-whether youth felt and thought that their school and teachers supported and provided activities for diverse intergroup interactions-and serious interpersonal violence, and explored whether this relation was mediated by civic engagement, ethnic identity, ethnocultural empathy, and positive peers. METHODS: An ethnically diverse sample of 324 middle school youth (mean age: 12.5 years; range: 11-15 years; sex: 50% female) from a city in northern California participated in the study. Analyses consisted of structural equation modeling with bootstrapping. RESULTS: The results revealed a negative association between school multiculturalism and interpersonal violence that was fully mediated by positive peers and civic engagement. Although school multiculturalism was positively associated with ethnic identity, ethnic identity, in turn, was not significantly associated with interpersonal violence. CONCLUSIONS: School multiculturalism is an important protective factor against youth violence by facilitating positive peer relationships and community engagement among youth. Teachers, administrators, and health officials need to consider the ways in which they can facilitate and encourage greater understanding, openness, and respect for diversity, and promote harmonious interactions among different groups at schools. Greater institutional support for school multiculturalism through implementation of tolerance curriculum and activities, for example, could in turn facilitate favorable youth outcomes. PMID- 21972990 TI - Weight-based victimization toward overweight adolescents: observations and reactions of peers. AB - BACKGROUND: Weight-based victimization has become increasingly reported among overweight youth, but little is known about adolescents' perceptions and observations of weight-based teasing and bullying. This study examined adolescents' observations of and reactions to weight-based victimization toward overweight students at school. METHODS: Adolescents (N = 1555) at 2 high schools in central Connecticut completed a questionnaire that examined their perceptions of how common weight-based victimization is compared to other forms of teasing at school, what types of weight-based teasing are frequently observed, who typical perpetrators of weight-based victimization are, and their own reactions to observed teasing incidents. Participants also completed the Fat Phobia Scale. RESULTS: Participants perceived being overweight as a primary reason that peers are victimized at school. At least 84% of participants observed overweight students being teased in a mean way and teased during physical activities, and 65% to 77% of students observed overweight and obese peers being ignored, avoided, excluded from social activities, having negative rumors spread about them, and being teased in the cafeteria. Most students also observed verbal threats and physical harassment toward overweight and obese students. Although the majority of participants felt comfortable stepping in to help an overweight peer who has been teased, many remain passive bystanders following these incidents. CONCLUSION: Youth perceive frequent and multiple forms of weight-based victimization. Schools' efforts to address weight bias and assist overweight and obese students are important. PMID- 21972991 TI - School travel planning: mobilizing school and community resources to encourage active school transportation. AB - BACKGROUND: Active school transport (AST), school travel using an active mode like walking, may be important to children's overall physical activity. A "school travel plan" (STP) documents a school's transport characteristics and provides an action plan to address school and neighborhood barriers to AST. METHODS: We conducted a pilot STP intervention at 12 schools in 4 Canadian provinces. Facilitators and school personnel created and implemented AST action plans. Parent's self-reports (N = 1489) were the basis for evaluating the intervention. A content analysis identified type, frequency, and perceived success of initiatives. RESULTS: School travel plans emphasized education and promotion, and AST activities and events. Capital improvement projects were more common at schools in older suburban neighborhoods, whereas enforcement was more common at schools in newer suburban neighborhoods. Rates of active transportation increased from 43.8% to 45.9%. At follow-up, 13.3% of households reported less driving. Parents/caregivers cited weather, convenience, and trip chaining as primary reasons for continued driving. CONCLUSION: The STP process may facilitate changes to patterns of school travel. An STP can expand a school's capacity to address transportation issues through mobilization of diverse community resources. Future STP initiatives may benefit from addressing convenience, safety through enforcement, and by examining how schools can be supported in implementing infrastructure improvements. PMID- 21972992 TI - Associations between academic achievement and psychosocial variables in adolescents with cystic fibrosis. AB - BACKGROUND: Cystic fibrosis (CF) is a chronic genetic disease that leads to the accumulation of thick mucus in multiple organ systems, leading to chronic lung infection and affecting the body's ability to absorb nutrients necessary for growth and development. This cross-sectional, correlational study examined the potential effects of CF on students' psychosocial and academic development. METHODS: Forty adolescents with CF completed a battery of neuropsychological and psychosocial measures. Their school records were reviewed to abstract information about standardized achievement testing results and grade point average (GPA). Academic outcomes were hypothesized to be associated with (1) self-efficacy, (2) disease and school-specific coping strategies, (3) attitude to school, and (4) depression. RESULTS: Cognitive and academic scores were within the normal range, and self-efficacy had the strongest association with standardized cognitive and academic measures and high school grades. School absences were associated with GPA, but not standardized test scores. CONCLUSION: Adolescents with CF require supports in school that foster their sense of self-efficacy and accommodations that address the learning time lost from extended health-related absences. PMID- 21972993 TI - Slap what?: an interactive lesson in nonverbal communication. PMID- 21972994 TI - Case of proximal calciphylaxis with protein S deficiency, successfully treated with multimodality therapy. PMID- 21972995 TI - Neither protogynous nor obligatory out-crossed: pollination biology and breeding system of the European Red List Fritillaria meleagris L. (Liliaceae). AB - For 4 years we studied pollination biology and breeding system of the critically endangered, Red List plant Fritillaria meleagris L. (Liliaceae), in the larger of the two remaining populations of the plant in SE Poland. Our observations indicated that, contrary to literature data, the species is not dichogamous nor is it obligatorily out-crossing. Selfing, although rare in natural populations, results in fully developed seeds. Flowers are visited by several insect species, mostly social and solitary bees. In spite of extremely low visitation rates to this early spring-flowering plant, the species is not pollen limited. Although the largest pollen loads are transferred by solitary bees, the key pollinators are bumblebees (mostly the most common species, Bombus terrestris and B. lapidarius) due to their seasonal and floral constancy, and tolerance of bad weather conditions. The current decline of the studied population seems not to be related to the species' pollination or breeding systems but to plant habitat loss. It is suggested, however, that in smaller populations, the species' dependence on generally rare pollinators and largely out-crossed breeding system may accelerate local extinction. PMID- 21972996 TI - Introduction of an electron withdrawing group on the hydroxyphenylnaphthol scaffold improves the potency of 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2) inhibitors. AB - Estrogen deficiency in postmenopausal women or elderly men is often associated with the skeletal disease osteoporosis. The supplementation of estradiol (E2) in osteoporotic patients is known to prevent bone fracture but cannot be administered because of adverse effect. As 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2) oxidizes E2 to its inactive form estrone (E1) and has been found in osteoblastic cells, it is an attractive target for the treatment of osteoporosis. Twenty-one novel, naphthalene-derived compounds have been synthesized and evaluated for their 17beta-HSD2 inhibition and their selectivity toward 17beta-HSD1 and the estrogen receptors (ERs) alpha and beta. Compound 19 turned out to be the most potent and selective inhibitor of 17beta-HSD2 in cell free assays and had a very good cellular activity in MDA-MB-231 cells, expressing naturally 17beta-HSD2. It also showed marked inhibition of the E1-formation by the rat and mouse orthologous enzymes and strong inhibition of monkey 17beta HSD2. It is thus an appropriate candidate to be further evaluated in a disease oriented model. PMID- 21972998 TI - Reproductive allocation and costs in gynodioecious Leucopogon melaleucoides (Ericaceae): implications for the evolution of gender dimorphism. AB - In dioecious species, females typically allocate more resources to reproduction and incur greater costs of reproduction than males. In gynodioecious species, sex based differences in reproductive allocation (RA) and costs have been less studied. Such knowledge, however, is relevant to address how females establish and increase in frequency in populations. We examine RA and reproductive costs by comparing fruit set, the proportion of biomass allocated to reproduction, and the responses of fruit set and vegetative growth to shoot defoliation in females and hermaphrodites in gynodioecious Leucopogon melaleucoides. Relative to hermaphrodites, females exhibited a two-fold fruit set advantage. Female fruit set increased proportionately with flower number, but hermaphrodite fruit set was reduced on plants with more flowers. Sex-based differences in allocation to other traits were small. Thus, female RA at flowering was similar to hermaphrodite RA, but was 1.4-fold greater at fruiting. Relative to controls, defoliation reduced fruit set and the percentage of shoots that produced new vegetative growth similarly in both sexes. However, females had a lower proportion of shoots with new growth overall. Further, defoliation on females reduced the dry mass of new growth by 44% compared with controls, whereas hermaphrodites were not affected. These results indicate a trade-off between reproduction and vegetative growth, and greater female costs of reproduction, particularly under resource-limiting conditions. In the absence of compensatory traits to offset higher female reproductive costs, such trade-offs have the potential to retard the spread of females in gynodioecious populations. PMID- 21972997 TI - Synthesis and biological evaluation of water-soluble progesterone-conjugated probes for magnetic resonance imaging of hormone related cancers. AB - Progesterone receptor (PR) is strongly associated with disease prognosis and therapeutic efficacy in hormone-related diseases such as endometriosis and breast, ovarian, and uterine cancers. Receptor status is currently determined by immunohistochemistry assays. However, noninvasive PR imaging agents could improve disease detection and help elucidate pathological molecular pathways, leading to new therapies and animal disease models. A series of water-soluble PR-targeted magnetic resonance imaging (MRI) probes were synthesized using Cu(I)-catalyzed click chemistry and evaluated in vitro and in vivo. These agents demonstrated activation of PR in vitro and preferential accumulation in PR(+) compared to PR( ) human breast cancer cells with low toxicity. In xenograft tumor models, the agents demonstrated enhanced signal intensity in PR(+) tumors compared to PR(-) tumors. The results suggest that these agents may be promising MRI probes for PR(+) diseases. PMID- 21972999 TI - Recommendations for the diagnosis and treatment of deep venous thrombosis and pulmonary embolism in pregnancy and the postpartum period. AB - Venous thromboembolism (VTE) in pregnancy and the postpartum is an important cause of maternal morbidity and mortality; yet, there are few robust data from clinical trials to inform an approach to diagnosis and management. Failure to investigate symptoms suggestive of pulmonary embolism (PE) is a consistent finding in maternal death enquiries, and clinical symptoms should not be relied on to exclude or diagnose VTE. In this consensus statement, we present our recommendations for the diagnosis and management of acute deep venous thrombosis (DVT) and PE. All women with suspected DVT in pregnancy should be investigated with whole leg compression ultrasonography. If the scan is negative and significant clinical suspicion remains, then further imaging for iliofemoral DVT maybe required. Imaging should be undertaken in all women with suspected PE, as the fetal radiation exposure with both ventilation/perfusion scans and CT pulmonary angiography is within safe limits. Low-molecular-weight heparin (LMWH) is the preferred therapy for acute VTE that occur during pregnancy. In observational cohort studies, using once-daily regimens appears adequate, in particular with the LMWH tinzaparin; however, pharmacokinetic data support twice daily therapy with other LMWH and is recommended, at least initially, for PE or iliofemoral DVT in pregnancy. Treatment should continue for a minimum duration of six months, and until at least six weeks postpartum. Induction of labour or planned caesarean section maybe required to allow an appropriate transition to unfractionated heparin to avoid delivery in women in therapeutic doses of anticoagulation. PMID- 21973000 TI - Age-related differences in warning symbol comprehension and training effectiveness: effects of familiarity, complexity, and comprehensibility. AB - Age-related changes in selective attention, inhibitory efficiency, and the ability to form new associations suggest that older adults may have greater difficulty with more complex and less comprehensible symbols. We examined comprehension of symbols varying in terms of ratings of familiarity, complexity, and comprehensibility, by younger (aged 18-35) and older (aged 55-70) adults. It was found that older adults have greater difficulty than younger adults in comprehending warning symbols and that accident scenario training improves comprehension. Regression analyses indicated that familiarity and comprehensibility were important in determining performance on the pre-training comprehension test by both younger and older adults. However, training eliminated the effects of stimulus characteristics for younger adults, while older adults' comprehension continued to be significantly influenced by comprehensibility. We suggest that symbol design incorporates cues to knowledge to facilitate the linkage between new knowledge (i.e. the warning symbol) and relevant knowledge in long-term memory. Statement of Relevance: Symbol characteristics play an important role in age-related differences in warning symbol comprehension. To optimise comprehension by older adults, symbols should have a clear relationship with areal-world referent. Alternatively, symbol design could incorporate cues to knowledge to facilitate the linkage between new knowledge and relevant knowledge in long-term memory. PMID- 21973001 TI - Decisional style, mood and work communication: email diaries. AB - To understand the use of technology to support interpersonal interaction, a theory of decisional style was applied to email use within the workplace. Previous research has used self-report and rating scales to address employee email behaviours, but this falls short of management's capability to monitor the actual behaviour. Thirty-nine employed individuals completed a five-day communication diary recording their actual behaviour upon receiving personal and work-related emails as well as the Melbourne Decision Making Questionnaire and the Depression Anxiety Stress Scales. It was found that vigilant individuals were more likely to use email in an efficient manner by deleting personal email and being less likely to open email later. Procrastinators, buckpassers and people experiencing high levels of negative affect were all more likely to delay dealing with email, which could be viewed as dealing with email in a less efficient manner. STATEMENT OF RELEVANCE: This work offers insights as to how people receive and process emails and is thus relevant to the development and implementation of collaborative technologies. Whilst other studies use individual's self-reports, this study uses a more accurate communication diary. Decisional style can predict the monitoring and response to electronic communication. PMID- 21973002 TI - Understanding social collaboration between actors and technology in an automated and digitised deep mining environment. AB - The purpose of this article is to develop knowledge and learning on the best way to automate organisational activities in deep mines that could lead to the creation of harmony between the human, technical and the social system, towards increased productivity. The findings showed that though the introduction of high level technological tools in the work environment disrupted the social relations developed over time amongst the employees in most situations, the technological tools themselves became substitute social collaborative partners to the employees. It is concluded that, in developing a digitised mining production system, knowledge of the social collaboration between the humans (miners) and the technology they use for their work must be developed. By implication, knowledge of the human's subject-oriented and object-oriented activities should be considered as an important integral resource for developing a better technological, organisational and human interactive subsystem when designing the intelligent automation and digitisation systems for deep mines. STATEMENT OF RELEVANCE: This study focused on understanding the social collaboration between humans and the technologies they use to work in underground mines. The learning provides an added knowledge in designing technologies and work organisations that could better enhance the human-technology interactive and collaborative system in the automation and digitisation of underground mines. PMID- 21973003 TI - The effects of focused attention training on the duration of novice drivers' glances inside the vehicle. AB - Several studies have documented that the failure of drivers to attend to the forward roadway for a period lasting longer than 2-3 s is a major cause of highway crashes. Moreover, several studies have demonstrated that novice drivers are more likely to glance away from the roadway than the experienced drivers for extended periods when attempting to do a task inside the vehicle. The present study examines the efficacy of a PC-based training programme (FOrward Concentration and Attention Learning, FOCAL) designed to teach novice drivers not to glance away forthese extended periods of time. A FOCAL-trained group was compared with a placebo-trained group in an on-road test, and the FOCAL-trained group made significantly fewer glances away from the roadway that were more than 2 s than the placebo-trained group. Other measures indicated an advantage for the FOCAL-trained group as well. Statement of relevance: Distracted driving is increasingly a problem, as cell phones, navigation systems, and other in-vehicle devices are introduced into the cabin of the automobile. A training programme is described that has beentested on the open road and can reduce the behaviours that lead to crashes caused by the distracted driving. PMID- 21973004 TI - The impact of cognitive workload on physiological arousal in young adult drivers: a field study and simulation validation. AB - Physiological measures provide a continuous and relatively non-invasive method of characterising workload. The extent to which such measures provide sensitivity beyond that provided by driving performance metrics is more open to question. Heart rate and skin conductance were monitored during actual highway driving in response to systematically increased levels of cognitive demand using an auditory delayed digit recall task. The protocol was consistent with an earlier simulator study, providing an opportunity to assess the validity of physiological measures recorded during driving simulation. The pattern of change in heart rate with increased cognitive demand was highly consistent between field and simulator. The findings meet statistical criteria for both relative and absolute validity, although there was a trend for absolute levels to be higher under actual driving conditions. For skin conductance level, the pattern in both environments was also quite similar and a reasonable case for overall relative validity can be made. STATEMENT OF RELEVANCE: Growing complexity and multiple demands on modern drivers' attention highlight the significance of determining whether physiological measures provide increased sensitivity in workload detection. Better understanding, including whether simulator assessments provide valid measures of real-world response patterns, has implications in evaluating and refining interface designs and for developing advanced workload managers. PMID- 21973005 TI - The associations between psychosocial workload and mental health complaints in different age groups. AB - The objective of the present study was to explore associations between psychosocial workload and mental health complaints in different age groups. A questionnaire was sent to 2021 employees of a Dutch railway company. Six aspects of psychosocial workload (work pressure, mental workload, emotional workload, autonomy, social support from colleagues and social support from supervisors) and three mental health outcomes (work-related fatigue, stress and burnout) were assessed. Associations between the aspects of psychosocial workload (distributed into tertiles) and health complaints were analysed by logistic regression analysis in four age groups (22-35, 36-45, 46-55 and 56-66 years old). In all age groups, worse work pressure was a significant risk factor for having mental health complaints. Worse emotional load in the younger employees and lack of social support in older employees were associated with a higher risk of having mental health complaints. Age-specific preventive measures should be implemented on both individual and group levels. STATEMENT OF RELEVANCE: With an ageing workforce, understanding relationships between age and work-related health ailments is increasingly important. This study found that emotional workload in younger and lack of social support in older employees were associated with a higher risk of mental health complaints. Work pressure was a risk factor in all age groups. PMID- 21973006 TI - Mechanical exposure among general practice dentists in Sweden and possible implications of rationalisation. AB - The present study investigates the dental work in terms of time distribution and mechanical exposure in value-adding work (VAW) and non-VAW. Further rationalisation of dental work would typically involve an increase in the proportion of VAW. Information on mechanical exposure within the classes of VAW and non-VAW may be used to predict possible implications of rationalisation. Sixteen dentists were investigated. Using a data logger, postures and movements were continuously recorded for each subject during the 4 h of work, which included the 45 min of video recording. Time distribution and mechanical exposure for the six different work activities identified were evaluated from the video recordings, using a loss analysis technique. VAW, which comprised 54% of the total working time, generally implied significantly more constrained mechanical exposures as compared with non-VAW. The results suggest that future rationalisation of dental work, involving a reduction of non-VAW, may increase the risk of developing musculoskeletal disorders. Statement of Relevance: The present study illustrates the potential effects of rationalisation on biomechanical exposures for dentists. The results highlight the significance of integrating ergonomic issues into the rationalisation process in dentistry in addition to ordinary workstation and tool design improvements performed by ergonomists. PMID- 21973007 TI - Effect of elliptic handle shape on grasping strategies, grip force distribution, and twisting ability. AB - A generic torque model for various handle shapes has been developed and evaluated using experimental data. Twelve subjects performed maximum isometric torques using circular and elliptic cylinders in medium and large sizes (circular: r = 25.4, 38.1 mm; elliptic: semi-major/minor axes = 30.9/19.3, 47.1/27.8 mm) finished with aluminium and rubber, in two opposite directions. Torque, grip force distribution, and finger position were recorded. Maximum torques were 25%, 7%, and 31% greater for the elliptic, large-size, and rubber-finished cylinders than for the circular, medium-size, and aluminium-finished cylinders, respectively. Greater torque for the elliptic cylinders was associated with 58% greater normal force that the subjects could generate for the elliptic than circular cylinders. The model suggests that greater torques for the large-size and rubber cylinders are related to long moment arms and greater frictional coupling at the hand-cylinder interface, respectively. Subjects positioned their hands differently depending on torque direction to maximise their normal force and torque generation. STATEMENT OF RELEVANCE: Desirable handle features for torque generation may be different from those for grip only. Design of handles per advantageous handle features (e.g., shape, size, and surface) may help increase people's torque strength and contribute to increased physical capacity of people. PMID- 21973008 TI - Handle height and expectation of cart movement affect the control of trunk motion at movement onset in cart pushing. AB - As unexpected sudden unloading of the trunk may cause low-back injury, the objective of the present study was to investigate whether handle height and the expectation of cart movement in pushing affect trunk control at movement onset. Eleven healthy male participants pushed a 200-kg cart with handles at shoulder and hip heights. The cart would suddenly move when externally released (externally triggered condition) or when static friction was overcome (self initiated condition). Before self-initiated cart movement, trunk stiffness and muscle activity were significantly higher than before an externally triggered onset at comparable pushing force. Lower muscle activity and trunk stiffness at shoulder height compared with the hip height before the onset resulted in higher trunk inclination after the onset. In conclusion, higher preparatory activation of trunk muscles serves to increase trunk stiffness in anticipation of cart movement and may reduce the impact of the perturbation associated with the onset of cart movement. STATEMENT OF RELEVANCE: Sudden cart movement in pushing causes an unexpected unloading perturbation to the trunk. This perturbation was shown to cause uncontrolled trunk movement, which may explain how pushing tasks can be associated with low-back injury. Effects of handle height and awareness of the subjects of the possible cart movement suggest directions for prevention. PMID- 21973011 TI - Modified bjork procedure for tricuspid atresia with pulmonary hypertension. AB - Tricuspid atresia (TA) is a rare and life-threatening cyanotic congenital heart anomaly, which is traditionally treated by the Fontan procedure. However, this procedure may be limited by the development of pulmonary hypertension and lead to long-term complications. The Bjork procedure offers an alternative for biventricular repair and right ventricular growth, especially in patients with pulmonary hypertension. We report a case of TA with pulmonary hypertension successfully treated with the modified Bjork procedure using an aortic homograft valved conduit. PMID- 21973012 TI - Two-, three-, and four-component magnetic multilayer onion nanoparticles based on iron oxides and manganese oxides. AB - Magnetic multilayered, onion-like, heterostructured nanoparticles are interesting model systems for studying magnetic exchange coupling phenomena. In this work, we synthesized heterostructured magnetic nanoparticles composed of two, three, or four components using iron oxide seeds for the subsequent deposition of manganese oxide. The MnO layer was allowed either to passivate fully in air to form an outer layer of Mn(3)O(4) or to oxidize partially to form MnO|Mn(3)O(4) double layers. Through control of the degree of passivation of the seeds, particles with up to four different magnetic layers can be obtained (i.e., FeO|Fe(3)O(4)|MnO|Mn(3)O(4)). Magnetic characterization of the samples confirmed the presence of the different magnetic layers. PMID- 21973013 TI - Stretchable graphene transistors with printed dielectrics and gate electrodes. AB - With the emergence of human interface technology, the development of new applications based on stretchable electronics such as conformal biosensors and rollable displays are required. However, the difficulty in developing semiconducting materials with high stretchability required for such applications has restricted the range of applications of stretchable electronics. Here, we present stretchable, printable, and transparent transistors composed of monolithically patterned graphene films. This material offers excellent mechanical, electrical, and optical properties, capable of use as semiconducting channels as well as the source/drain electrodes. Such monolithic graphene transistors show hole and electron mobilities of 1188 +/- 136 and 422 +/- 52 cm(2)/(V s), respectively, with stable operation at stretching up to 5% even after 1000 or more cycles. PMID- 21973014 TI - Fundamental reaction pathway and free energy profile for hydrolysis of intracellular second messenger adenosine 3',5'-cyclic monophosphate (cAMP) catalyzed by phosphodiesterase-4. AB - As important drug targets for a variety of human diseases, cyclic nucleotide phosphodiesterases (PDEs) are a superfamily of enzymes sharing a similar catalytic site. We have performed pseudobond first-principles quantum mechanical/molecular mechanical-free energy perturbation (QM/MM-FE) and QM/MM Poisson-Boltzmann surface area (PBSA) calculations to uncover the detailed reaction mechanism for PDE4-catalyzed hydrolysis of adenosine 3',5'-cyclic monophosphate (cAMP). This is the first report on QM/MM reaction-coordinate calculations including the protein environment of any PDE-catalyzed reaction system, demonstrating a unique catalytic reaction mechanism. The QM/MM-FE and QM/MM-PBSA calculations revealed that the PDE4-catalyzed hydrolysis of cAMP consists of two reaction stages: cAMP hydrolysis (stage 1) and bridging hydroxide ion regeneration (stage 2). The stage 1 includes the binding of cAMP in the active site, nucleophilic attack of the bridging hydroxide ion on the phosphorus atom of cAMP, cleavage of O3'-P phosphoesteric bond of cAMP, protonation of the departing O3' atom, and dissociation of hydrolysis product (AMP). The stage 2 includes the binding of solvent water molecules with the metal ions in the active site and regeneration of the bridging hydroxide ion. The dissociation of the hydrolysis product is found to be rate-determining for the enzymatic reaction process. The calculated activation Gibbs free energy of >=16.0 and reaction free energy of -11.1 kcal/mol are in good agreement with the experimentally derived activation free energy of 16.6 kcal/mol and reaction free energy of -11.5 kcal/mol, suggesting that the catalytic mechanism obtained from this study is reliable and provides a solid base for future rational drug design. PMID- 21973015 TI - Hormonal control of endoreduplication in sugar beet (Beta vulgaris L.) seedlings growing in vitro. AB - The effect on endoreduplication in sugar beet (Beta vulgaris L.) seedlings of five plant hormones in MS medium, ethylene, 24-epibrassinolide (EBR), gibberellic acid (GA(3) ), kinetin and 1-naphthaleneacetic acid (NAA), as well as a combination of kinetin and NAA at two different concentrations, was studied using flow cytometry. Analyses of DNA content in nuclei of the root, hypocotyl and cotyledons of seedlings growing in vitro were performed during their early development, starting from when the root was 0.5-1.0 cm long until expansion of the first pair of leaves. The proportions of nuclei with different DNA contents were established and the mean C-value calculated. The presence of exogenous plant hormones changed endoreduplication intensity, although to different extents, depending on the organ and developmental stage. Ethylene and NAA stimulated the process, while EBR and kinetin suppressed it and GA did not clearly affect it. PMID- 21973016 TI - Successful prophylactic use of recombinant activated factor VII (rFVIIa) in a patient with congenital FVII deficiency and inhibitors to FVII. PMID- 21973017 TI - Overexpression of Dsk2/dUbqln results in severe developmental defects and lethality in Drosophila melanogaster that can be rescued by overexpression of the p54/Rpn10/S5a proteasomal subunit. AB - Polyubiquitin receptors execute the targeting of polyubiquitylated proteins to the 26S proteasome. In vitro studies indicate that disturbance of the physiological balance among different receptor proteins impairs the proteasomal degradation of polyubiquitylated proteins. To study the physiological consequences of shifting the in vivo equilibrium between the p54/Rpn10 proteasomal and the Dsk2/dUbqln extraproteasomal polyubiquitin receptors, transgenic Drosophila lines were constructed in which the overexpression or RNA interference-mediated silencing of these receptors can be induced. Flies overexpressing Flag-p54 were viable and fertile, without any detectable morphological abnormalities, although detectable accumulation of polyubiquitylated proteins demonstrated a certain level of proteolytic disturbance. Flag-p54 was assembled into the 26S proteasome and could fully complement the lethal phenotype of a p54 null mutant Drosophila line. The overexpression of Dsk2 caused severe morphological abnormalities in the late pupal stages, leading to pharate adult lethality, accompanied by a huge accumulation of highly polyubiquitylated proteins. The lethal phenotype of Dsk2 overexpression could be rescued in a double transgenic line coexpressing Flag Dsk2 and Flag-p54. Although the double transgenic line was viable and fertile, it did not restore the proteolytic defects; the accumulation of the highly polyubiquitylated proteins was even more severe in the double transgenic line. Significant differences were found in the Dsk2-26S proteasome interaction in Drosophila melanogaster as compared with Saccharomyces cerevisiae. In yeast, Dsk2 can interact only with DeltaRpn10 proteasomes and not with the wild-type one. In Drosophila, Dsk2 does not interact with Deltap54 proteasomes, but the interaction can be fully restored by complementing the Deltap54 deletion with Flag-p54. PMID- 21973018 TI - Dermoscopic detection of nail fold capillary abnormality in patients with systemic sclerosis. AB - The diagnosis of systemic sclerosis (SSc) is often difficult. The purpose of the present study was to find the distribution of nail fold capillary abnormality in SSc. Sixty-two patients with SSc (male : female = 7:55, age 21-86 years, mean 60.1) admitted to the outpatient clinics were studied. Eighteen age- and sex matched normal subjects, 28 patients with systemic lupus erythematosus (SLE) and 10 with dermatomyositis (DM) were also studied. Nail fold capillary loops were observed under immersion oil at a magnification of *40 with a light microscope. Dilated capillaries, nail fold bleeding and avascular areas were found by dermoscopic observation. The distribution of dilated capillaries, nail fold bleeding and avascular areas in normal controls showed in one (5.6%), one (5.6%) and four cases (22.2%), respectively. The distribution of dilated capillaries, nail fold bleeding and avascular area in SSc patients showed in 27 cases (43.5%), eight cases (12.9%) and 16 cases (25.8%), respectively. The distribution of dilated capillaries and/or nail fold bleeding in SSc patients (29/62, 46.8%) was significantly elevated than that of normal controls (2/18, 11.1%) (P < 0.01). The distribution of overall abnormality in SSc (30/62, 48.4%) showed no significant difference compared with that of normal controls (4/18, 22.2%). Sensitivity and specificity for dilated capillaries and/or nail fold bleeding and overall nail fold abnormality in SSc patients compared with normal controls was calculated as 40.8% and 93.5%, 34.8% and 88.2%, respectively. Dermoscopic observation of dilated capillaries and/or nail fold bleeding is a sensitive and specific method for the detection of SSc. PMID- 21973020 TI - Incidence of severe adverse events requiring hospital care after trastuzumab infusion for metastatic breast cancer: a nationwide survey using an administrative claim database. PMID- 21973019 TI - Inhibition of the mammalian target of rapamycin blocks epilepsy progression in NS Pten conditional knockout mice. AB - PURPOSE: Increased activity of mTOR Complex 1 (mTORC1) has been demonstrated in cortical dysplasia and tuberous sclerosis complex, as well as in animal models of epilepsy. Recent studies in such models revealed that inhibiting mTORC1 with rapamycin effectively suppressed seizure activity. However, seizures can recur after treatment cessation, and continuous rapamycin exposure can adversely affect animal growth and health. Here, we evaluated the efficacy of an intermittent rapamycin treatment protocol on epilepsy progression using neuron subset-specific Pten (NS-Pten) conditional knockout mice. METHODS: NS-Pten knockouts were treated with a single course of rapamycin during postnatal weeks 4 and 5, or intermittently over a period of 5 months. Epileptiform activity was monitored using video-electroencephalography (EEG) recordings, and mossy fiber sprouting was evaluated using Timm staining. Survival and body weight were assessed in parallel. KEY FINDINGS: NS-Pten knockouts treated with a single course of rapamycin had recurrence of epilepsy 4-7 weeks after treatment ended. In contrast, epileptiform activity remained suppressed, and survival increased if knockout mice received additional rapamycin during weeks 10-11 and 16-17. Aberrant mossy fiber sprouting, present by 4 weeks of age and progressing in parallel with epileptiform activity, was also blocked by rapamycin. SIGNIFICANCE: These findings demonstrate that a single course of rapamycin treatment suppresses epileptiform activity and mossy fiber sprouting for several weeks before epilepsy recurs. However, additional intermittent treatments with rapamycin prevented this recurrence and enhanced survival without compromising growth. Therefore, these studies add to the growing body of evidence implicating an important role for mTORC1 signaling in epilepsy. PMID- 21973021 TI - Is there evidence of optimisation for carbon efficiency in plant proteomes? AB - Flowering plants, angiosperms, can be divided into two major clades, monocots and dicots, and while differences in amino acid composition in different species from the two clades have been reported, a systematic analysis of amino acid content and distribution remains outstanding. Here, we show that monocot and dicot proteins have developed distinct amino acid content. In Arabidopsis thaliana and poplar, as in the ancestral moss Physcomitrella patens, the average mass per amino acid appears to be independent of protein length, while in the monocots rice, maize and sorghum, shorter proteins tend to be made of lighter amino acids. An examination of the elemental content of these proteomes reveals that the difference between monocot and dicot proteins can be largely attributed to their different carbon signatures. In monocots, the shorter proteins, which comprise the majority of all proteins, are made of amino acids with less carbon, while the nitrogen content is unchanged in both monocots and dicots. We hypothesise that this signature could be the result of carbon use and energy optimisation in fast growing annual Poaceae (grasses). PMID- 21973022 TI - Notch signalling pathway in tooth development and adult dental cells. AB - Notch signalling is a highly conserved intercellular signal transfer mechanism that includes canonical and non-canonical pathways. It regulates differentiation and proliferation of stem/progenitor cells by means of para-inducing effects. Expression and activation of Notch signalling factors (receptors and ligands) are critical not only for development of the dental germ but also for regeneration of injured tissue associated with mature teeth. Notch signalling plays key roles in differentiation of odontoblasts and osteoblasts, calcification of tooth hard tissue, formation of cusp patterns and generation of tooth roots. After tooth eruption, Notch signalling can also be triggered in dental stem cells of the pulp, where it induces them to differentiate into odontoblasts, thus generating fresh dentine tissue. Other signalling pathways, such as TGFbeta, NF-kappaB, Wnt, Fgf and Shh also interact with Notch signalling during tooth development. PMID- 21973023 TI - The cytotoxic potential of interleukin-15-stimulated cytokine-induced killer cells against leukemia cells. AB - BACKGROUND AIMS: Cytokine-induced killer (CIK) cells may serve as an alternative approach to adoptive donor lymphocyte infusions (DLI) for patients with acute leukemia relapsing after haplo-identical hematopoietic stem cell transplantation (HSCT). We investigated the feasibility of enhancing CIK cell-mediated cytotoxicity by interleukin (IL)-15 against acute myeloid and lymphoblastic leukemia/lymphoma cells. METHODS: CIK cells were activated using IL-2 (CIK(IL-2)) or IL-15 (CIK(IL-15)) and phenotypically analyzed by fluorescence-activated cell sorting (FACS). Cytotoxic potential was measured by europium release assay. RESULTS: CIK(IL-2) cells showed potent cytotoxicity against the T-lymphoma cell line H9, T-cell acute lymphoblastic leukemia (T-ALL) cell line MOLT-4 and subtype M4 acute myeloid leukemia (AML) cell line THP-1, but low cytotoxicity against the precursor B (pB)-cell ALL cell line Tanoue. IL-15 stimulation resulted in a significant enhancement of CIK cell-mediated cytotoxicity against acute lymphoblastic leukemia/lymphoma cell lines as well as against primary acute myeloid and defined lymphoblastic leukemia cells. However, the alloreactive potential of CIK(IL-15) cells remained low. Further analysis of CIK(IL-15) cells demonstrated that the NKG2D receptor is apparently involved in the recognition of target cells whereas killer-cell immunoglobulin-like receptor (KIR)-HLA mismatches contributed to a lesser extent to the CIK(IL-15) cell-mediated cytotoxicity. In this context, CD3 (+) CD8 (+) CD25 (+) CD56(-) CIK(IL-15) cell subpopulations were more effective in the lysis of AML cells, in contrast with CD56 (+) CIK(IL-15) cells, which showed the highest cytotoxic potential against ALL cells. CONCLUSIONS: This study provides the first evidence that CIK(IL-15) cells may offer a therapeutic option for patients with refractory or relapsed leukemia following haplo-identical HSCT. PMID- 21973024 TI - Implementation of a configurable laboratory information management system for use in cellular process development and manufacturing. AB - BACKGROUND AIMS: Regulatory requirements for the manufacturing of cell products for clinical investigation require a significant level of record-keeping, starting early in process development and continuing through to the execution and requisite follow-up of patients on clinical trials. Central to record-keeping is the management of documentation related to patients, raw materials, processes, assays and facilities. METHODS: To support these requirements, we evaluated several laboratory information management systems (LIMS), including their cost, flexibility, regulatory compliance, ongoing programming requirements and ability to integrate with laboratory equipment. After selecting a system, we performed a pilot study to develop a user-configurable LIMS for our laboratory in support of our pre-clinical and clinical cell-production activities. We report here on the design and utilization of this system to manage accrual with a healthy blood donor protocol, as well as manufacturing operations for the production of a master cell bank and several patient-specific stem cell products. RESULTS: The system was used successfully to manage blood donor eligibility, recruiting, appointments, billing and serology, and to provide annual accrual reports. Quality management reporting features of the system were used to capture, report and investigate process and equipment deviations that occurred during the production of a master cell bank and patient products. CONCLUSIONS: Overall the system has served to support the compliance requirements of process development and phase I/II clinical trial activities for our laboratory and can be easily modified to meet the needs of similar laboratories. PMID- 21973025 TI - Efficient cellular delivery of beta-galactosidase mediated by NrTPs, a new family of cell-penetrating peptides. AB - Nucleolar targeting peptides (NrTPs), a recently developed family of cell penetrating peptides, have been shown to be very efficient in entering cells and accumulating in their nucleoli. In this work, we have used conjugates of NrTP6 (YKQSHKKGGKKGSG) covalently linked to beta-galactosidase in order to demonstrate the capacity of NrTP for intracellular delivery of large molecules. NrTP6/beta galactosidase conjugates, prepared by maleimide-based chemistry, were stable and enzymatically active on the standard 4-methylumbelliferyl beta-d galactopyranoside substrate. Their translocation into HeLa cells, monitored by beta-galactosidase activity as a readout of the uptake, showed efficient cellular entry and thus demonstrated the potential of NrTPs for intracellular delivery of large-size cargos with preservation of biological activity. PMID- 21973027 TI - In vivo confocal microscopy visualization of presumed lymph vessels in a case of corneal transplant rejection. PMID- 21973028 TI - Trypanosoma cruzi connatal transmission in dogs with Chagas disease: experimental case report. AB - Trypanosoma cruzi connatal transmission was studied in male and female mongrel dogs. Both dogs were experimentally infected, after which on the 20(th) day, lymphoadenomegaly and fever were found. Four months postinfection, they mated. At this time, Chagas disease was confirmed by two different diagnostic tests. The electrocardiogram and echocardiogram taken at the eight postinoculation month showed data consistent with ischemia, local conduction abnormalities and hypertrophy, as well as a diminished ejection fraction and left ventricular dilation, respectively. Four puppies were born and after weaning had weakness, progressive weight loss, and chronic diarrhea. Necropsy of all four showed digestive alterations and cardiac dilation. Serology in the offspring was positive for Chagas disease. The histopathological study demonstrated a cardiac chronic inflammatory process, although no parasites were found. Clinical data and serological determinations are consistent with death from advanced Chagas disease. PMID- 21973026 TI - Human versus porcine mesenchymal stromal cells: phenotype, differentiation potential, immunomodulation and cardiac improvement after transplantation. AB - Although mesenchymal stromal cells (MSCs) have been applied clinically to treat cardiac diseases, it is unclear how and to which extent transplanted MSCs exert their beneficial effects. To address these questions, pre-clinical MSC administrations are needed for which pigs appear to be the species of choice. This requires the use of porcine cells to prevent immune rejection. However, it is currently unknown to what extent porcine MSCs (pMSCs) resemble human MSCs (hMSCs). Aim of this study was to compare MSC from porcine bone marrow (BM) with human cells for phenotype, multi-lineage differentiation potential, immune modulatory capacity and the effect on cardiac function after transplantation in a mouse model of myocardial infarction. Flow cytometric analysis revealed that pMSC expressed surface antigens also found on hMSC, including CD90, MSCA-1 (TNAP/W8B2 antigen), CD44, CD29 and SLA class I. Clonogenic outgrowth was significantly enriched following selection of CD271+ cells from BM of human and pig (129 +/- 29 and 1961 +/- 485 fold, respectively). hMSC and pMSC differentiated comparably into the adipogenic, osteogenic or chondrogenic lineages, although pMSC formed fat much faster than hMSC. Immuno-modulation, an important feature of hMSC, was clearly demonstrated for pMSC when co-cultured with porcine peripheral blood cells stimulated with PMA and pIL-2. Finally, pMSC transplantation after myocardial infarction attenuated adverse remodelling to a similar extent as hMSC when compared to control saline injection. These findings demonstrate that pMSCs have comparable characteristics and functionality with hMSCs, making reliable extrapolation of pre-clinical pMSC studies into a clinical setting very well possible. PMID- 21973029 TI - Aberrant regulation and function of Src family tyrosine kinases: their potential contributions to glutamate-induced neurotoxicity. AB - Excitotoxicity, a major cause of neuronal death in acute and chronic neurodegenerative diseases and conditions such as stroke and Parkinson's disease, is initiated by overstimulation of glutamate receptors, leading to calcium overload in affected neurons. The sustained high concentration of intracellular calcium constitutively activates a host of enzymes, notably the calcium-activated proteases calpains, neuronal nitric oxide synthase (nNOS) and NADPH oxidase (NOX), to antagonise the cell survival signalling pathways and induce cell death. Upon overactivation by calcium, calpains catalyse limited proteolysis of specific cellular proteins to modulate their functions; nNOS produces excessive amounts of nitric oxide (NO), which, in turn, covalently modifies specific enzymes by S nitrosylation; and NOX produces excessive amounts of reactive oxygen species (ROS) to inflict damage to key metabolic enzymes. Presumably, key regulatory enzymes governing cell survival and cell death are aberrantly modified and regulated by calpains, NO and ROS in affected neurons; these aberrantly modified enzymes then cooperate to induce the death of affected neurons. c-Src, an Src family kinase (SFK) member, is one of the aberrantly regulated enzymes involved in excitotoxic neuronal death. Herein we review how SFKs are functionally linked to the glutamate receptors and the biochemical and structural basis of the aberrant regulation of SFKs. Results in the literature suggest that SFKs are aberrantly activated by calpain-mediated truncation and S-nitrosylation. Thus, the aberrantly activated SFKs are targets for therapeutic intervention to reduce the extent of brain damage caused by stroke. PMID- 21973030 TI - Synthesis of 1,2-dihydroxyindolizidines from 1-(2-pyridyl)-2-propen-1-ol. AB - 1-(2-Pyridyl)-2-propen-1-ol, obtained by vinylation of commercially available picolinaldehyde, resulted a good starting material for the synthesis of the indolizidine skeleton. In particular, a simple process involving bromination, reduction, and nucleophilic substitution (via elimination and addition) allowed an easy conversion of the starting material into (+/-)-lentiginosine in ~27% overall yield. PMID- 21973031 TI - Emotional responses in spider fear are closely related to picture awareness. AB - Theories of emotion propose that responses to emotional pictures can occur independently of whether or not people are aware of the picture content. Because evidence from dissociation paradigms is inconclusive, we manipulated picture awareness gradually and studied whether emotional responses varied with degree of awareness. Spider fearful and non-fearful participants viewed pictures of spiders and flowers at four levels of backward masking while electrodermal activity and heart rate were measured continuously. Recognition ratings confirmed that participants' picture awareness decreased with masking. Critically, effects of spider fear on emotion ratings and heart rate also decreased with masking. These findings suggest that effects of spider fear on emotion ratings and heart rate are closely related to picture awareness. PMID- 21973032 TI - Cardiopulmonary bypass and its direct effects on neonatal piglet kidney morphology. AB - Renal failure after open heart surgery is a serious complication even in the pediatric population. The aim of the present study was to analyze morphological changes after cardiopulmonary bypass (CPB) surgery in a neonatal piglet model. The kidneys of newborn piglets sacrificed 6 h after CPB were examined (CPB; n = 4) regarding tubular dilatation, vacuole formation, leukocytic infiltration, epithelial destruction, and interstitial edema. Thereafter, the findings were compared with the morphology of normal (untreated) neonatal piglet kidneys (control; n = 4). All changes but the interstitial edema were statistically significant if compared with the normal renal tissue: tubular dilatation (CPB vs. control P < 0.05), vacuole formation (CPB vs. control P < .05), leukocytic infiltration (CPB vs. control P < 0.05), and epithelial destruction (CPB vs. control P < 0.001). In conclusion, CPB induces significant changes in the morphology of the neonatal piglet kidneys. PMID- 21973033 TI - Response of Trifolium repens to UV-B radiation: morphological links to plant productivity and water availability. AB - This study used nine populations of Trifolium repens L. (white clover) to investigate possible relationships between plant morphological attributes and responses to ultraviolet-B (UV-B) radiation. Plants were exposed to 0 or 13.3 kJ.m(-2) .day(-1) UV-B for 12 weeks. Drought was applied in parallel to these treatments during the last 4 weeks of the experiment to test whether limited moisture availability would alter morphological UV-B responses. UV-B affected plant morphology under well-watered conditions, reducing leaf size by 15%, leaf number by 5% and stolon elongation by 19%. The number of leaf primordia in the apical bud was decreased by 4% under UV-B, and by 12% under drought. In drought exposed plants, leaf size was reduced by 50%, leaf number by 30% and stolon elongation by 60%. In addition, drought reduced specific leaf area (SLA) by 33% and increased leaf percentage dry mass (PDM) by 40%. UV-B-induced reduction in plant biomass in the T. repens populations was associated with higher plant productivity and this was further linked to larger leaf size as well as to lower PDM. In conclusion, the findings suggest that morphological attributes conferring fast potential growth under productive conditions carry a cost in the form of lower biomass accumulation under UV-B. PMID- 21973034 TI - Association of systemic psoriasis therapies and incidence of myocardial infarction. PMID- 21973035 TI - Characterization of metabolite quantitative trait loci and metabolic networks that control glucosinolate concentration in the seeds and leaves of Brassica napus. AB - * Glucosinolates are a major class of secondary metabolites found in the Brassicaceae, whose degradation products are proving to be increasingly important for human health and in crop protection. * The genetic and metabolic basis of glucosinolate accumulation was dissected through analysis of total glucosinolate concentration and its individual components in both leaves and seeds of a doubled haploid (DH) mapping population of oilseed rape/canola (Brassica napus). * The quantitative trait loci (QTL) that had an effect on glucosinolate concentration in either or both of the organs were integrated, resulting in 105 metabolite QTL (mQTL). Pairwise correlations between individual glucosinolates and prior knowledge of the metabolic pathways involved in the biosynthesis of different glucosinolates allowed us to predict the function of genes underlying the mQTL. Moreover, this information allowed us to construct an advanced metabolic network and associated epistatic interactions responsible for the glucosinolate composition in both leaves and seeds of B. napus. * A number of previously unknown potential regulatory relationships involved in glucosinolate synthesis were identified and this study illustrates how genetic variation can affect a biochemical pathway. PMID- 21973037 TI - This issue: assessment of pediatric mental health. PMID- 21973036 TI - Pediatric mental health issues. PMID- 21973038 TI - Male infant with shallow respirations. PMID- 21973039 TI - Bipolar disorder in children and adolescents. PMID- 21973040 TI - Diagnosis of autism spectrum disorders. PMID- 21973041 TI - Assessment of attention-deficit/hyperactivity disorder. PMID- 21973042 TI - Anxiety disorders in pediatric primary care. PMID- 21973043 TI - Assessment of disruptive behavior disorders. PMID- 21973044 TI - Pediatric depression detection methods. PMID- 21973045 TI - Chronic kidney disease stage 5 as the prognostic complement of International Staging System for multiple myeloma. AB - BACKGROUND: Reversal of renal impairment (RI) in patients with multiple myeloma (MM) has been evaluated using the estimated glomerular filtration rate (eGFR(MDRD) ) formula developed by the Modification of Diet in Renal Disease study group. However, the prognostic impact of eGFR(MDRD) at diagnosis of MM is not well studied, particularly its use in conjunction with the International Staging System (ISS). METHODS: Newly diagnosed patients with MM were enrolled between 1996 and 2007. Data on clinical features, laboratory tests, and overall survival were compared in terms of corresponding eGFR(MDRD). RESULTS: A total of 387 patients with MM (median age, 71 yr) were enrolled. At diagnosis, 56% had ISS stage III disease; the median values of serum creatinine (SCr) and eGFR(MDRD) were 1.4 mg/dL and 38.2 mL/min/1.73 m(2) , respectively. Thirty-four percent of patients had SCr of >= 2.0 mg/dL, and 81.2% had chronic kidney disease stages 3-5 (CKD 3-5). Higher CKD stages were significantly more common in men, older patients (>= 65 yr), and those with Durie-Salmon and ISS stage III, light-chain diseases, anemia, thrombocytopenia, hypercalcemia, elevated serum beta(2) microglobulin, or lactate dehydrogenase. In the Cox regression model, CKD 4-5 or CKD 5 alone was independently associated with poor survival. A diagnosis of CKD 5 was shown to be useful in identifying the subgroup of ISS-III patients at high risk - those with a median overall survival of 7.2 months. CONCLUSIONS: Our study demonstrates the prognostic impact of eGFR(MDRD) in patients with MM and CKD 5 as the ISS-independent surrogate predictor of poorest prognosis. PMID- 21973046 TI - Autologous bone marrow cell therapy for patients with peripheral arterial disease: a meta-analysis of randomized controlled trials. AB - OBJECTIVE: Early-phase clinical trials suggest that autologous bone-marrow derived cells (BMCs) may have a positive effect on patients with severe peripheral arterial disease (PAD). However, the therapeutic effects of BMCs treatment in various aspects remain controversial. RESEARCH DESIGN AND METHODS: We conducted a meta-analysis using data from randomized controlled trials (RCTs) by comparing autologous BMCs therapy with controls in patients with severe PAD. Pubmed, EMBASE, EBSCO and the Cochrane Central Register of Controlled Trials ( to approximately April 2011) were searched. RESULTS: Seven RCTs with 276 patients were included. Pooled comparisons of studies found that BMCs therapy significantly improved ankle-brachial index (ABI) by 0.10 (95% CI, 0.07 to 0.14; p < 0.00001), transcutaneous oxygen tension (TcO(2)) by 13.39 mmHg (95% CI, 6.69 to 20.1 mmHg; p < 0.0001) and pain-free walking distance by 119.91 m (95% CI, 90.71 to 149.11 m; p < 0.00001). BMCs therapy significantly decreased scale of rest pain by 1.13 (95% CI, -1.71 to -0.54, p = 0.0002) and helped heal ulcers (OR, 7.17; 95% CI, 2.66 to 19.32; p < 0.0001). CONCLUSIONS: Our analysis based on seven RCTs suggests that autologous BMCs therapy, has a beneficial effect on physiologic and anatomic parameters in patients with severe PAD. PMID- 21973047 TI - A tunable plasmon resonance in gold nanobelts. AB - Plasmonic nanowires with sub-100-nm rectangular cross sections were found to exhibit a strong transverse plasmon peak at visible wavelengths. By correlating atomic force microscopy measurements of individual nanobelts with their dark field scattering spectra, it is seen that the transverse peak tunes with cross sectional aspect ratio. Simulations revealed that the scattering plasmonic modes are transverse antisymmetric excitations across the nanobelt width. Unlike larger diameter silver nanowires, these nanobelts exhibit sharp, tunable plasmon resonances similar to those of nanoparticles. PMID- 21973048 TI - Designed post-self-assembly structural and functional modifications of a truncated tetrahedron. AB - Post-self-assembly modifications of a discrete metal-organic supramolecular structure have been developed. Such modifications allow the properties of the self-assembled supramolecular species to be changed in a simple and efficient manner (>90% yield). Initiated by the application of chemical stimuli, the post self-assembly modifications described herein result in three distinct changes to the supramolecular system: an individual building-block component change, an overall structural modification, and a functional evolution of a [6+4] metal organic supramolecular structure. The three modifications have been carefully examined by a range of characterization methods, including NMR and UV-vis spectroscopy, electrospray ionization mass spectrometry, pulsed field gradient spin echo NMR measurements, electrochemical analysis, and computational simulations. PMID- 21973049 TI - TNF-alpha inhibits aquaporin 5 expression in human salivary gland acinar cells via suppression of histone H4 acetylation. AB - Sjogren's syndrome is a systemic autoimmune disease characterized by reductions in salivary and lacrimal secretions. The mechanisms underlying these reductions remain unclear. We have previously shown that TNF-alpha plays an important role in the destruction of acinar structures. Here we examined TNF-alpha's function in the expression of aquaporin (AQP) 5 in human salivary gland acinar cells. Immortalized human salivary gland acinar (NS-SV-AC) cells were treated with TNF alpha, and then the expression levels of AQP5 mRNA and protein were analysed. In addition, the mechanisms underlying the reduction of AQP5 expression by TNF-alpha treatment were investigated. TNF-alpha-treatment of NS-SV-AC cells significantly suppressed the expression levels of AQP5 mRNA and protein, and reduced the net fluid secretion rate. We examined the expression and activation levels of DNA methyltransferases (Dnmts) in NS-SV-AC cells treated with TNF-alpha. However, no significant changes were observed in the expression or activation levels of Dnmt1, Dnmt3a or Dnmt3b. Although we also investigated the role of NF-kappaB activity in the TNF-alpha-induced suppression of AQP5 expression in NS-SV-AC cells, we detected similar TNF-alpha suppression of AQP5 expression in non transfected cells and in a super-repressor form of IkappaBalpha cDNA-transfected cell clones. However, interestingly, chromatin immunoprecipitation analysis demonstrated a remarkable decrease in levels of acetylated histone H4 associated with the AQP5 gene promoter after treatment with TNF-alpha in NS-SV-AC cells. Therefore, our results may indicate that TNF-alpha inhibition of AQP5 expression in human salivary gland acinar cells is due to the epigenetic mechanism by suppression of acetylation of histone H4. PMID- 21973050 TI - Special issue: engineering toxins for 21st-century therapies: introduction. AB - This special issue on 'Engineering toxins for 21st century therapies' provides a critical review of the current state of multifaceted aspects of toxin research by some of the leading researchers in the field. It also highlights the clinical potential and challenges for development of novel biologics based on engineered toxin derived products. PMID- 21973051 TI - Pulmonary complications of sickle cell disease. AB - The pulmonary complications of sickle cell disease are a major cause of morbidity and mortality in affected patients. The acute chest syndrome (ACS) is a leading cause of death in patients with sickle cell disease and has a multifactorial etiology. Hydroxyurea (HU), stem cell transplantation (SCT) and chronic transfusions are known to prevent the recurrence of ACS. Careful management of patients admitted for pain crises and surgery including use of incentive spirometry is critical in preventing this complication. Pulmonary hypertension is well known to be associated with sickle cell disease and patients with pulmonary hypertension have increased mortality. Asthma is also commonly seen in patients with sickle cell disease and is associated with a more complicated course. Chronic lung disease develops in a significant proportion of patients with sickle cell disease. PMID- 21973053 TI - Germination, survival and growth of three vascular plants on biological soil crusts from a Mexican tropical desert. AB - Information about the effects of biological soil crusts (BSC) on germination, seedling survival and growth of vascular plants is controversial because they can have positive, neutral or negative effects. This controversy may be because most studies conducted until now have just analysed one or two recruitment stages independently. To understand the BSC effects on vascular plants, it is necessary to consider each stage of the recruitment process and synthesise all this information. The goal of this study was twofold. First, we analyse germination, seedling survival and growth of three vascular plants (Agave marmorata, Prosopis laevigata and Neobuxbaumia tetetzo) on BSC (cyanobacteria and mixed crust) from a tropical desert region of south-central Mexico. Second, we synthesise the information to determine the total effect of BSC on plant species performance. We conducted experiments under controlled conditions to evaluate the proportion of germinated seeds, proportion of surviving seedlings and seedling dry weight in BSC and bare soil. Results showed that BSC have different effects on germination, seedling survival and growth of plant species. Plant species performance was qualitatively higher on BSC than bare soil. The highest performance of A. marmorata and P. laevigata was observed on cyanobacteria and mixed crusts, respectively. The highest performance of N. tetetzo was on both crust types. PMID- 21973052 TI - Evaluation of air-QTM intubating laryngeal airway as a conduit for tracheal intubation in infants--a pilot study. AB - BACKGROUND: Air-QTM intubating laryngeal airway (ILA) has been used successfully as a conduit for tracheal intubation in pediatric difficult airway. However, its use as an airway device and conduit for intubation in infants is not yet evaluated. AIMS: The primary objective was to evaluate ILA as a conduit for tracheal intubation in infants, and secondary objectives were to evaluate ILA in terms of ease of insertion and ventilation, oropharyngeal leak pressure (OLP), glottic view, and complications. METHODS: Twenty infants with normal airway were included. After induction of general anesthesia and neuromuscular blockade, ILA (size 1.0/1.5) was inserted. Fiberoptic bronchoscope (FOB)-guided intubation and removal of ILA with the stabilizing stylet was attempted. RESULTS: The mean age and weight of the infants were 7.5 +/- 2.3 months and 7.3 +/- 1.8 kg. The ILA sizes 1.0 and 1.5 were inserted in 10 infants each according to the weight of the infants. The mean OLP was 18.5 +/- 1.8 cm H2O, and mean time for insertion of ILA was 13.3 +/- 3.9 s. Glottic view was grade I in 6, grade II in 1, grade III in 4, and grade IV in nine infants. Tracheal intubation was successful in 19/20 infants. The mean endotracheal tube (ETT) insertion time and mean total time (ILA insertion to the confirmation of ETT placement) were 95.6 +/- 32.3 s and 306.42 +/- 120.2 s respectively. CONCLUSION: The ILA is a safe and easy-to-use supraglottic airway device for intubation with FOB in infants with normal airway. Insertion and removal of ILA are easy with satisfactory oropharyngeal seal and ventilation. PMID- 21973054 TI - Biologically active arborinane-type triterpenoids and anthraquinones from Rubia yunnanensis. AB - Twelve new arborinane-type triterpenoids (1-12) and four new anthraquinones (13 16), together with 50 known compounds, were isolated from the roots of Rubia yunnanensis. The structures of 1-16 were elucidated by spectroscopic data analysis and chemical methods. All compounds were evaluated for their cytotoxic, antibacterial, and antifungal activities. Rubiyunnanol C (5) is the first example of an arborinane-type triterpenoid with a double bond at C-8-C-9. PMID- 21973055 TI - Accelerating the domestication of trees using genomic selection: accuracy of prediction models across ages and environments. AB - * Genomic selection is increasingly considered vital to accelerate genetic improvement. However, it is unknown how accurate genomic selection prediction models remain when used across environments and ages. This knowledge is critical for breeders to apply this strategy in genetic improvement. * Here, we evaluated the utility of genomic selection in a Pinus taeda population of c. 800 individuals clonally replicated and grown on four sites, and genotyped for 4825 single-nucleotide polymorphism (SNP) markers. Prediction models were estimated for diameter and height at multiple ages using genomic random regression best linear unbiased predictor (BLUP). * Accuracies of prediction models ranged from 0.65 to 0.75 for diameter, and 0.63 to 0.74 for height. The selection efficiency per unit time was estimated as 53-112% higher using genomic selection compared with phenotypic selection, assuming a reduction of 50% in the breeding cycle. Accuracies remained high across environments as long as they were used within the same breeding zone. However, models generated at early ages did not perform well to predict phenotypes at age 6 yr. * These results demonstrate the feasibility and remarkable gain that can be achieved by incorporating genomic selection in breeding programs, as long as models are used at the relevant selection age and within the breeding zone in which they were estimated. PMID- 21973056 TI - SNX-BAR-mediated endosome tubulation is co-ordinated with endosome maturation. AB - Endosomal sorting is essential for cell homeostasis. Proteins targeted for degradation are retained in the maturing endosome vacuole while others are recycled to the cell surface or sorted to the biosynthetic pathway via tubular transport carriers. Sorting nexin (SNX) proteins containing a BAR (for Bin Amphiphysin-Rvs) domain are key regulators of phosphoinositide-mediated, tubular based endosomal sorting, but how such sorting is co-ordinated with endosomal maturation is not known. Here, using well-defined Rab GTPases as endosomal compartment markers, we have analyzed the localization of SNX1 [endosome-to-trans Golgi network (TGN) transport as part of the SNX-BAR-retromer complex], SNX4 (cargo-recycling from endosomes to the plasma membrane) and SNX8 (endosomes-to TGN trafficking in a retromer-independent manner). We show that these SNX-BARs are primarily localized to early endosomes, but display the highest frequency of tubule formation at the moment of early-to-late endosome transition: the Rab5-to Rab7 switch. Perturbing this switch shifts SNX-BAR tubulation to early endosomes, resulting in SNX1-decorated tubules that lack retromer components VPS26 and VPS35, suggesting that both early and late endosomal characteristics of the endosome are important for SNX-BAR-retromer-tubule formation. We also establish that SNX4, but not SNX1 and SNX8, is associated with the Rab11-recycling endosomes and that a high frequency of SNX4-mediated tubule formation is observed as endosomes undergo Rab4-to-Rab11 transition. Our study therefore provides evidence for fine-tuning between the processes of endosomal maturation and the formation of endosomal tubules. As tubulation is required for SNX1-, SNX4- and SNX8-mediated sorting, these data reveal a previously unrecognized co-ordination between maturation and tubular-based sorting. PMID- 21973057 TI - When the alternative would have been better: counterfactual reasoning and the emergence of regret. AB - Counterfactual reasoning about how events could have turned out better is associated with the feeling of regret. However, developmental studies show a discrepancy between the onset of counterfactual reasoning (at 3 years) and the feeling of regret (at 6 years). In four experiments we explored possible reasons. Experiment 1 (3- to 6-year-old children) and Experiment 2 (adult control) show that even when regret is assessed more directly than in previous studies (e.g., Amsel & Smalley, 2000) only adults but not children regret their decision. Experiment 3 (3- to 14-year-old children) suggests that double-questioning- asking children how happy they are with what they got before and after they had seen what they could have got--creates false positive indications of regret in the youngest children and that--when controlling for false positives--regret is not evident before 9 years. However, children before this age make a difference between attractive (three candies) and less attractive (one candy) items (Experiment 4; 6- to 8-year-old children). Taken together, this suggests that before 9 years of age children base their judgements solely on what they got without taking into account what they could have got. PMID- 21973058 TI - Prediction of flowering time in Brassica oleracea using a quantitative trait loci based phenology model. AB - Uniformly developing plants with a predictable time to harvest or flowering under unfavourable climate conditions are a major breeding goal in crop species. The main flowering regulators and their response to environmental signals have been identified in Arabidopsis thaliana and homologues of flowering genes have been mapped in many crop species. However, it remains unclear which genes determine within and across genotype flowering time variability in Brassica oleracea and how genetic flowering time regulation is influenced by environmental factors. The goal of this study is model-based prediction of flowering time in a B. oleracea DH-line population using genotype-specific and quantitative trait loci (QTL) model input parameters. A QTL-based phenology model accounting for genotypic differences in temperature responses during vernalisation and non-temperature sensitive durations from floral transition to flowering was evaluated in two field trials. The model was parameterised using original genotype-specific model input parameters and QTL effects. The genotype-specific model parameterisation showed accurate predictability of flowering time if floral induction was promoted by low temperature (R(2) = 0.81); unfavourably high temperatures reduced predictability (R(2) = 0.65). Replacing original model input parameters by QTL effects reduced the capability of the model to describe across-genotype variability (R(2) = 0.59 and 0.50). Flowering time was highly correlated with a model parameter accounting for vernalisation effects. Within-genotype variability was significantly correlated with the same parameter if temperature during the inductive phase was high. We conclude that flowering time variability across genotypes was largely due to differences in vernalisation response, although it has been shown elsewhere that the candidate FLOWERING LOCUS C (FLC) did not co segregate with flowering time in the same population. FLC independent vernalisation pathways have been described for several species, but not yet for B. oleracea. PMID- 21973059 TI - Operative management and outcomes in children with congenital bleeding disorders: a retrospective review at a single haemophilia treatment centre. AB - Establishing haemostasis for surgical procedures in children with inherited bleeding disorders is challenging. Providers are often hesitant to undertake surgeries in children with bleeding disorders out of fear of bleeding complications. To review the preoperative management and haemorrhagic complications of children with inherited bleeding disorders at our institution, we conducted a retrospective electronic medical record review from 1999 to 2010. Primary focus was review of bleeding complications and factor replacement strategies. A total of 168 procedures were performed in 66 children. Fifteen procedures (8%) in four children were performed in the presence of high-titre factor inhibitors. Procedures included central venous catheter (CVL) placement or revision (41%), otolaryngology procedures (23%), dental (11%), non-synovectomy orthopaedic procedures (8%), synovectomy (5%), circumcision (5%) and miscellaneous (7%). All patients received preoperative factor replacement (100% in haemophilia patients) followed by various factor replacement regimens postoperatively. No deaths or life-threatening bleeding occurred with any procedure. Twelve of 168 procedures (7%) were complicated by bleeding. Tonsillectomy was the most common procedure complicated by haemorrhage 4 of 15 (26%) followed by nasal surgery (3/7 bleeds = 43%). The CVL surgeries were remarkably free of complications with only 1/69 (1.4%) with bleeding. Surgical procedures are safe in children with bleeding disorders with adequate planning and factor replacement. Bleeding remains a problem in a subset of patients and requires ongoing haematological involvement and oversight. Delayed bleeding following T&A was especially common and suggests a need for close follow-up and ongoing factor coverage for this group of patients. PMID- 21973060 TI - Prognostic value of OCT4 in primary intracranial germinoma: a single institute analysis of 31 cases. AB - OCT4 expresses variably in primary intracranial germinomas. In this study, we tested our hypothesis that such variation of OCT4 is predictive of outcome in primary intracranial germinomas. Thirty-one histologically identified CNS germinoma patients were enrolled in our study. We collected medical data, immunohistochemically evaluated the OCT4 expression level, and followed up all patients from April 2001 to May 2010. We found that 7 of the 31 patients expressed OCT4 weakly, 11 expressed OCT4 moderately, and 13 expressed OCT4 strongly. No significant correlation between the OCT4 expression level and clinicopathological characteristics was observed. WV-CS combined treatment modality showed a better 5-year progression-free survival (PFS) rate than other treatment modalities and a low expression level of OCT4 showed a significantly better 5-year PFS. In both the WV-CS combined treatment modality and other treatments modality group, patients received a better 5-year PFS and had a lower level of OCT4 expression. As a result, we suggest OCT4 as a probable prognostic marker for intracranial germinoma. PMID- 21973061 TI - Antibiotic-impregnated catheters for the prevention of CSF shunt infections: a systematic review and meta-analysis. AB - CSF infections are a serious complication of CSF shunts and external ventricular drains (EVDs). Antibiotic-impregnated catheters (AIC) have been tried in order to minimise the risk of such infections. OBJECTIVES: To conduct a systematic review and a meta-analysis comparing AICs versus non-AICs used as ventriculo-peritoneal (VP) shunts or external ventricular drains (EVDs) in the neonatal population. The secondary aim was to include data from a paediatric and adult population if insufficient information was available from neonatal studies. DATA SOURCES: PubMed (March 2011), EMBASE (March 2011), CENTRAL (1980-March 2011), and CINAHL (March 2011) were searched. Study selection. Both randomised controlled trials (RCTs) and observational studies were included. RESULTS: Only three observational studies reported on the use of AI-VP shunt catheters in the neonatal population. Meta-analysis found a statistically significant difference favouring AI shunts (RR: 0.37; CI: 0.16, 0.86; p = 0.02). Twelve studies (one RCT, 11 observational; n = 3284) compared AI versus non-AI VP shunts in a paediatric and adult population. The RCT showed a trend towards benefit using the AICs (RR: 0.38; 95% CI: 0.11, 1.30; p = 0.12). A meta-analysis of the 11 observational studies showed a significant benefit in the AI group (RR: 0.37; CI: 0.23, 0.60; p = 0.0001; n = 3149). Similar benefits were noted for AI-EVDs in RCTs (RR: 0.19; 95% CI: 0.05, 0.64; p = 0.01; n = 472, two studies) and observational studies (RR: 0.31; 95 CI: 0.13, 0.74; p = 0.009; n = 2415, five studies). CONCLUSIONS: A meta-analysis of mainly observational studies suggests that AICs may be an effective way of reducing the incidence of shunt and EVD infections. Well-designed multi-centre RCTs are urgently needed. PMID- 21973062 TI - Atypical presentation of delayed communicating hydrocephalus after supratentorial glioma resection with opening of the ventricles. AB - We report four cases of communicating hydrocephalus, requiring shunt placement, in the subset of patients whose ventricles were breached at the time of glioma resection (a total 97 cases over 3 years). The hydrocephalus in these cases presented without ventricular dilatation on computed tomography (CT) scanning, and in 3 cases without headache. Failure to progress, visual deterioration or cerebrospinal fluid (CSF) leak in the post-operative patient after tumour resection with ventricular opening should alert clinicians to the possibility of hydrocephalus, despite the absence of headache or ventriculomegaly, and lumbar puncture should be performed without delay. PMID- 21973063 TI - The minimum time for cranioplasty insertion from craniectomy is six months to reduce risk of infection--a case series of 82 patients. AB - OBJECTIVE: Cranioplasty is carried out for cosmesis, protection and also for neurological improvement following cranial defect. Infection post cranioplasty is problematic. We look at the outcome from 10 years of cranioplasty patients, and aim to see if there is a correlation between infection and time to insertion of cranial plate. METHODS: A retrospective case series identifying all cranioplasty patients between 1998-2008 using the maxillofacial laboratory data log of all plates that were made during this time. Data was yielded from the clinical case notes and the microbiology database. The outcome measure was infection defined as removal of cranioplasty plate. RESULTS: Total cranioplasties performed = 82. Infected cranioplasties = 9 (7 titanium 2 acrylic). An 11% infection rate of cranioplasties. Craniectomy due to trauma, with cranioplasty occurring between 0 to 6 months had the greatest number of infective cases, with 8 out of 9 occuring in this period (p value = 0.0076). CONCLUSION: Cranioplasty carried out at a minimum of 6 months post craniectomy limits the risk of infection. PMID- 21973064 TI - Introduction: special issue on tomboys and tomboyism. AB - This article provides a critical introduction to, as well as an overview of the articles within, this special issue. The opening portion briefly discusses the history of tomboyism as both a cultural concept and embodied phenomenon. Then, the subsequent paragraphs provide a brief summary of the five essays that comprise this themed edition. In so doing, the Introduction addresses the current state of scholarship on tomboys and tomboyism, while it also highlights possible areas for future study. PMID- 21973065 TI - The tomboyism of faith: spiritual tomboyism in the cult of Sainte Foy. AB - This article offers a reading of premodern, spiritual tomboyism as evident in the cult of Sainte Foy in France during the ninth to eleventh centuries. It draws attention to the signs of differently gendered and aged masculinities in the female child saint. Martyred at the cusp of puberty, Sainte Foy remains forever suspended in her gender development. Bernard of Angers, in the Liber miraculorum, portrays Foy as a trickster tomboy whose miracles are known as her "jokes." But beyond the historical Foy and the textual Foy, there is a third Foy who is embodied in a reliquary statue with an adult male head. In times of social upheaval, Sainte Foy, whose earthly presence is manifest in her relics and reliquary statue, functions as a local patronus who protects her monastery, properties, and devotees. Her male-headed reliquary further affirms her identity as a holy warrior of Christ who fights to uphold the Peace of God. As trickster tomboy and warrior-patronus, Sainte Foy hovers at and crosses over the boundaries of both gender- and age-based identities and practices. PMID- 21973066 TI - Tomboy as protective identity. AB - The tomboy in contemporary U.S. culture is a complex identity, providing meaning to many girls and women. In this article, we argue tomboy as a gendered social identity also provides temporary "protections" to girls and women in three main ways. First, tomboy identity can excuse masculine-typed behavior in girls and women and, in doing so, protect women from presumptions about sexual reputation and sexual orientation. Second, tomboy identities can provide some protection for lesbian girls and women who prefer to not divulge their sexual orientation. And, third, tomboy identity can gain women limited privilege to spaces for which masculinity is an unspoken requirement. The temporary nature of the protections provided to tomboys undermines the ability of tomboys to truly transcend the binary gender system. PMID- 21973067 TI - Tomboy chic: re-fashioning gender rebellion. AB - This article explores the recent celebration of tomboy chic as the latest attempt to discursively intervene on female masculinity. First, the article contextualizes tomboy identity within theories of female masculinity and butch identity. Next, it maps out the proliferation of tomboy recuperation narratives throughout popular culture, from fashion magazines and daytime television to online advice sites. Framing tomboy identity as delayed maturation in need of an intervention, this re-fashioning of tomboy identity as style-over-substance jeopardizes an important outlet for gender rebellion. PMID- 21973068 TI - Studs and protest-hypermasculinity: the tomboyism within black lesbian female masculinity. AB - In this article, I use the ethnographic work I conducted in the summer of 2009 with Black lesbian women from South Carolina to show how Black female masculinity has been influenced by historically based constructions of Black gender. I will argue that these studs strategically construct and perform their masculinity in ways that shield them from sexism, racism, and homophobia both in and out of their Black community. By adopting the particular type of masculinity common among their Black male peers, these studs can gain access to some levels of male privilege and power which, in turn, can act as useful defense mechanisms against multiple types of discrimination and oppression. PMID- 21973069 TI - Online women-seeking-women personal ads and the deployment of "tomboy" identities. AB - This article examines online women-seeking-women (WSW) personal ads that engage with tomboy identities and ideologies. This research demonstrates the importance of body and physicality among lesbian personal ads and the diversity of women using online personal ads. The meaning of "tomboy" in the language of WSW personal ads suggests major themes of use including: as an intermediate identity distinct within a butch/femme dichotomy, as a tempering agent for traditional femininity, as a fluid construct of personality, physicality, and body, as an understood descriptor of a particular aesthetic or physicality, and as synonymous with butch. To be a tomboy is to be simultaneously understood as a social stereotype, but also as complex, fluid, and of multiple meanings. PMID- 21973072 TI - Richter syndrome in chronic lymphocytic leukaemia manifesting only as tumorous hepatomegaly. PMID- 21973074 TI - Inspiratory training increases insulin sensitivity in elderly patients. AB - AIM: Physiological degeneration in the aging process can cause a notable decline in carbohydrate metabolism. Respiratory training has been recommended to elderly patients in an attempt to prevent or minimize the alterations to the cardiorespiratory, metabolic and cognitive systems and to improve their quality of life. The objective of this work was to investigate the influence of inspiratory muscular training, with Threshold, on insulin resistance in elderly people. METHODS: This study included 14 insulin resistant elderly volunteers, ranging in age from 61 to 82 years old. Insulin resistance was confirmed using the homeostatic model assessment. The patients were divided into two groups: experimental and control. The program lasted 12 weeks, with 30-min training daily using Threshold to train the inspiratory muscles. RESULTS: The experimental group had improved insulin resistance, with decreased glycemia and insulin requirements, a lower homeostatic model assessment of insulin resistance, and increased respiratory force and performance. CONCLUSION: The small sample does not allow for conclusions, but we can suggest that inspiratory muscular training improves insulin sensitivity in elderly patients with insulin resistance. PMID- 21973075 TI - Wnt and SHH in prostate cancer: trouble mongers occupy the TRAIL towards apoptosis. AB - Prostate cancer is a serious molecular disorder that arises because of reduction in tumour suppressors and overexpression of oncogenes. The malignant cells survive within the context of a three-dimensional microenvironment in which they are exposed to mechanical and physical cues. These signals are, nonetheless, deregulated through perturbations to mechanotransduction, from the nanoscale level to the tissue level. Increasingly sophisticated interpretations have uncovered significant contributions of signal transduction cascades in governing prostate cancer progression. To dismantle the major determinants that lie beneath disruption of spatiotemporal patterns of activity, crosstalk between various signalling cascades and their opposing and promoting effects on TRAIL-mediated activities cannot be ruled out. It is important to focus on that molecular multiplicity of cancer cells, various phenotypes reflecting expression of a variety of target oncogenes, reversible to irreversible, exclusive, overlapping or linked, coexist and compete with each other. Comprehensive investigations into TRAIL-mediated mitochondrial dynamics will remain a worthwhile area for underlining causes of tumourigenesis and for unravelling interference options. PMID- 21973076 TI - Phosphorus magnetic resonance spectroscopy in malformations of cortical development. AB - PURPOSE: The aim of this study was to evaluate phospholipid metabolism in patients with malformations of cortical development (MCDs). METHODS: Thirty-seven patients with MCDs and 31 control subjects were studied using three-dimensional phosphorus magnetic resonance spectroscopy ((31)P-MRS) at 3.0 T. The voxels in the lesions and in the frontoparietal cortex of the control subjects were compared (the effective volumes were 12.5 cm(3)). Robust quantification methods were applied to fit the time-domain data to the following resonances: phosphoethanolamine (PE); phosphocholine (PC); inorganic phosphate (Pi); glycerophosphoethanolamine (GPE); glycerophosphocholine (GPC); phosphocreatine (PCr); and alpha-, beta-, and gamma-adenosine triphosphate (ATP). We also estimated the total ATP (ATP(t) = alpha-+beta-+gamma-ATP), phosphodiesters (PDE = GPC+GPE), phosphomonoesters (PME = PE+PC), and the PME/PDE, PCr/ATP(t) and PCr/Pi ratios. The magnesium (Mg(2+)) levels and pH values were calculated based on PCr, Pi, and beta-ATP chemical shifts. KEY FINDINGS: Compared to controls and assuming that a p-value < 0.05 indicates statistical significance, the patients with MCDs exhibited significantly lower pH values and higher Mg(2+) levels. In addition, the patients with MCDs had lower GPC and PDE and an increased PME/PDE ratio. SIGNIFICANCE: Mg(2+) and pH are important in the regulation of bioenergetics and are involved in many electrical activity pathways in the brain. Our data support the idea that neurometabolic impairments occur during seizure onset and propagation. The GPC, PDE, and PME/PDE abnormalities also demonstrate that there are membrane turnover disturbances in patients with MCDs. PMID- 21973078 TI - Decreased structural defence of an invasive thistle under warming. AB - Plant structural defences play a key role in preventing fitness loss due to herbivory. However, how structural defences are affected by potential climate change is rarely examined. We examined how leaf morphological traits that relate to the structural defence of an invasive thistle, Carduus nutans, change in a warmer climate. We manipulated warming using open-top chambers (OTCs) and examined the morphology of leaves at three different positions (the 5th, 10th and 15th leaves, counted from the top of the plant) in two destructive summer censuses. We found that structural defence traits were different under ambient versus warmed conditions. Prickle densities (both the number of prickles per leaf area and the number of prickles per leaf mass) were significantly lower in plants grown in a warmer climate. Our results suggest that plant structural defences may be reduced under warming, and therefore should be considered when examining species' responses to climate change. PMID- 21973077 TI - Comprehensive proteomic study identifies serpin and cystatin antiproteases as novel correlates of HIV-1 resistance in the cervicovaginal mucosa of female sex workers. AB - Not all individuals exposed to HIV-1 become infected, and evidence from HIV-1 highly exposed seronegative women (HIV-1-resistant) suggests that mucosal factors in the female genital tract, the first site of contact for the virus, are playing a role. To better understand factors mediating protection from HIV-1, we performed a large clinical study using the tools of systems biology to fully characterize the cervicovaginal mucosa proteome in HIV-1-resistant women. Cervicovaginal lavage fluid was collected from 293 HIV-1-resistant, uninfected, and infected sex workers and analyzed by 2D-LC LTQ-FT-MS. Of the more than 360 unique proteins identified, 41 were differentially abundant (>3-fold cutoff) in HIV-1-resistant women. The majority of over-abundant proteins were antiproteases (>40%), some with described anti-inflammatory and anti-HIV-1 activity. Quantification of specific anti-HIV-1 antiproteases Serpin A1, Serpin A3, and Cystatin B and an epithelial antiprotease A2ML1 found them to be significantly over-abundant in HIV-1-resistant women (p = 0.004; p = 0.046; p = 0.0003; and p = 0.04, respectively). Expression levels were not correlated to sexual practices or other epidemiological factors. Mucosal antiprotease levels correlated with pro inflammatory cytokine concentration (p = <0.0001), but independently of pro inflammatory cytokine levels in HIV-1-resistant women including TNF-alpha, IL-1 alpha, IL-1 beta, IL-6, and IL-8. This comprehensive systems biology approach identifies mucosal serpins and cystatins as novel correlates of HIV-1-resistance. This represents the first study characterizing these factors in the female genital tract. PMID- 21973079 TI - Amelanotic lentigo maligna managed with topical imiquimod. PMID- 21973080 TI - Solution- and solid-state conformations of C(alpha)-alkyl analogues of methylphenidate (Ritalin) salts: avoidance of gauche(+)gauche(-) interactions. AB - Alkyl analogues of methylphenidate (Ritalin) salts are slow onset, long duration dopamine reuptake inhibitors with a potential use as a cocaine abuse pharmacotherapy. X-ray crystallographic studies and nuclear magnetic resonance (NMR) investigations strongly suggest that avoidance of sterically unfavorable gauche(-)gauche(+) orientations effectively influences both the C(alpha)-alkyl side chain conformation and the formation of a predominant rotamer about the CH CH bond ligating piperidine and C(Ar)R moieties. The favored CH-CH rotamer in D(2)O and in CD(2)Cl(2) of the pharmacologically interesting i-Bu and CH(2)-cyc Pnt (RS,RS)-salts has the same antiperiplanar arrangement that was found in the crystal structures, although there clearly is a fast equilibrium involving smaller amounts of synclinal partners. While the rotamer in the (RS,SR)-i-Bu HCl crystal structure exhibits a synclinal orientation for the vicinal pair of adjacent methine protons, the weighted time-averaged arrangement for these protons becomes almost completely antiperiplanar when the crystals are dissolved in D(2)O. Increased steric congestion around the CH-CH bond in the analogous N methyl tertiary ammonium salts seems to augment the quantity of the preferred rotamer within the mixture. The stereochemistry of the species observed via NMR seems to arise from specific combinations of N-methyl orientation and avoidance of sterically unfavorable gauche(-)gauche(+) arrangements. PMID- 21973081 TI - Effects of transient overexpression or knockdown of cytochrome P450 reductase on reactive oxygen species generation and hypoxia reoxygenation injury in liver cells. AB - 1. Literature data suggest that the electron-donating enzyme, cytochrome P450 reductase (CPR), might act as a source of reactive oxygen species (ROS). However, the role of CPR in pathophysiological conditions associated with oxidative stress is unknown. The aim of the present study was to study the role of CPR in the generation of ROS and cellular injury under basal conditions, and after simulated in vitro ischaemia-reperfusion (IR). 2. Plasmid DNA or siRNA approaches were used to transiently overexpress or knockdown the human CPR gene in rat liver epithelial (WB-F344) or human hepatoblastoma (HepG2) cells, respectively. The generation of ROS and/or cellular injury was then studied under the basal conditions and after simulated IR (4 h of ischaemia plus 30 min of reoxygenation). 3. Under the basal conditions, transient overexpression of CPR protein in WB-F344 cells caused a 90% increase in the CPR activity, which was associated with a 100% increase in the ROS production. In contrast, after simulated IR, a 2.5-fold higher CPR activity did not significantly affect the magnitude of ROS generation or cell death. Similarly, although the knockdown of CPR protein resulted in a significant reduction (~30%) in the CPR activity, the ROS production was not substantially altered after simulated IR in HepG2 cells. 4. Our data suggest that CPR plays a major role in the ROS generation by liver cells under the basal conditions. However, the role of CPR in the ROS generation during simulated in vitro IR injury in these cells is minimal, if any. PMID- 21973082 TI - Numerical modeling of anisotropic fiber bundle behavior in oxygenators. AB - Prediction of flow patterns through oxygenator fiber bundles can allow shape optimization so that efficient gas exchange occurs with minimal thrombus formation and hemolysis. Computational fluid dynamics (CFD) simulations can be used to predict three-dimensional flow velocities and flow distribution from spatially dependent variables and they allow estimations of erythrocyte residence time within the fiber bundle. This study builds upon previous work to develop an accurate numerical model for oxygenators, which would allow for accelerated iterations in oxygenator shape and diffuser plate design optimization. Hollow fiber flow channels were developed to permit experimental calculation of fluid permeability in two directions: main flow along the hollow fiber and perpendicular to the hollow fibers. Commercial software was used to develop three dimensional CFD models of the experimental flow channels and an anisotropic porous media model for oxygenators from these experimental results. The oxygenator model was used to predict pressure loss throughout the device, visualize blood distribution within the fiber bundle, and estimate erythrocyte residence time within the bundle. Experimental flow channels measurements produced a streamwise permeability of 1.143e(-8) m(2) and transverse permeability of 2.385e(-9) m(2) . These permeabilities, coupled with previous work with volume porosity, were used to develop the numerical model of anisotropic behavior through porous fiber bundles, which indicated a more uniform flow field throughout the oxygenator. Incorporation of known anisotropic fiber bundle behavior in previous numerical models more accurately represents fluid behavior through an oxygenator fiber bundle. CFD coupled with experimental validation can produce a powerful tool for oxygenator design and development. PMID- 21973083 TI - Airway tissue engineering. AB - INTRODUCTION: Prosthetic replacements, autologous tissue transfer and allografts have so far failed to offer functional solutions for the treatment of long circumferential tracheal defects and loss of a functioning larynx. Interest has therefore turned increasingly to the field of tissue-engineering which applies the principles and methods of bioengineering, material science, cell transplantation and life sciences in an effort to develop in vitro biological substitutes able to restore, maintain or improve tissue and organ function. AREAS COVERED: This article gives an overview of the tissue-engineering approach to airway replacement and will describe the encouraging results obtained so far in tracheal regeneration. The recent advances in the field of tissue-engineering have provided a new attractive approach towards the concept of functional substitutes and may represent an alternative to the shortage of suitable grafts for reconstructive airway surgery. We summarize fundamental questions, as well as future directions in airway tissue engineering. EXPERT OPINION: The replacement of active movement, as would be necessary to replace an entire larynx introduces another order of magnitude of complexity, although progress in this area is starting to bear fruit. In addition, the stem cell field is advancing rapidly, opening new avenues for this type of therapy. PMID- 21973084 TI - Transistor-like behavior of single metalloprotein junctions. AB - Single protein junctions consisting of azurin bridged between a gold substrate and the probe of an electrochemical tunneling microscope (ECSTM) have been obtained by two independent methods that allowed statistical analysis over a large number of measured junctions. Conductance measurements yield (7.3 +/- 1.5) * 10(-6)G(0) in agreement with reported estimates using other techniques. Redox gating of the protein with an on/off ratio of 20 was demonstrated and constitutes a proof-of-principle of a single redox protein field-effect transistor. PMID- 21973085 TI - Age-related changes in the contractile and passive arterial properties of murine mesenteric small arteries are altered by caveolin-1 knockout. AB - Caveolin-1, an integral protein of caveolae, is associated with multiple cardiovascular signalling pathways. Caveolin-1 knockout (KO) mice have a reduced lifespan. As changes in artery structure and function are associated with ageing we have investigated the role of caveolin-1 ablation on age-related changes of small artery contractility and passive mechanical properties. Mesenteric small arteries isolated from 3 and 12-month wild-type (WT) and caveolin-1 KO mice were mounted on a pressure myograph and changes in passive and functional arterial properties were continuously monitored. In WT mice ageing was associated with a reduction in arterial contractility to noradrenaline which was reversed by inhibition of nitric oxide synthase with L-NNA. Similarly, in 3-month-old mice, caveolin-1 KO reduced contractility to noradrenaline by an L-NNA-sensitive mechanism. However, ageing in caveolin-1 KO mice was not associated with any further change in contractility. In WT mice ageing was associated with an increased passive arterial diameter and cross-sectional area (CSA), consistent with outward remodelling of the arterial wall, and a reduced arterial distensibility. Caveolin-1 ablation at 3 months of age resulted in similar changes in passive arterial properties to those observed with ageing in WT animals. However, ageing in caveolin-1 KO mice resulted in a reduced arterial CSA indicating different effects on passive structural characteristics from that observed in WT mice. Thus, caveolin-1 mice show abnormalities of small mesenteric artery function and passive mechanical characteristics indicative of premature vascular ageing. Moreover, caveolin-1 ablation modulates the age-related changes usually observed in mesenteric arteries of WT mice. PMID- 21973086 TI - Identification and verification of heat shock protein 60 as a potential serum marker for colorectal cancer. AB - Colorectal cancer (CRC) is a major public health issue worldwide, and novel tumor markers may contribute to its efficient management by helping in early detection, prognosis or surveillance of disease. The aim of our study was to identify new serum biomarkers for CRC, and we followed a phased biomarker discovery and validation process to obtain an accurate preliminary assessment of potential clinical utility. We compared colonic tumors and matched normal tissue from 15 CRC patients, using two-dimensional difference gel electrophoresis (2D-DIGE), and identified 17 proteins that had significant differential expression. These results were further confirmed by western blotting for heat shock protein (HSP) 60, glutathione-S-transferase Pi, alpha-enolase, T-complex protein 1 subunit beta, and leukocyte elastase inhibitor, and by immunohistochemistry for HSP60. Using mAbs raised against HSP60, we developed a reliable (precision of 5-15%) and sensitive (0.3 ng.mL(-1)) immunoassay for the detection of HSP60 in serum. Elevated levels of HSP60 were found in serum from CRC patients in two independent cohorts; the receiver-operating characteristic curve obtained in 112 patients with CRC and 90 healthy controls had an area under the curve (AUC) of 0.70, which was identical to the AUC of carcinoembryonic antigen. Combination of serum markers improved clinical performance: the AUC of a three-marker logistic regression model combining HSP60, carcinoembryonic antigen and carbohydrate antigen 19-9 reached 0.77. Serum HSP60 appeared to be more specific for late stage CRC; therefore, future studies should evaluate its utility for determining prognosis or monitoring therapy rather than early detection. PMID- 21973087 TI - Abscisic acid-regulated responses of aba2-1 under osmotic stress: the abscisic acid-inducible antioxidant defence system and reactive oxygen species production. AB - We investigated the interaction among abscisic acid (ABA), reactive oxygen species (ROS) and antioxidant defence system in the transduction of osmotic stress signalling using Arabidopsis thaliana WT (Columbia ecotype, WT) and an ABA deficient mutant (aba2-1). For this, 50 MUm ABA and osmotic stress, induced with 40% (w/v) polyethylene glycol (PEG8000; -0.7 MPa), were applied to WT and aba2-1 for 6, 12 or 24 h. Time course analysis was undertaken for determination of total/isoenzyme activity of the antioxidant enzymes, superoxide dismutase (SOD; EC 1.15.1.1), catalase (CAT; EC 1.11.1.6), ascorbate peroxidase (APX; EC 1.11.1.11), NADPH oxidase (NOX; EC 1.6.3.1) activity; scavenging activity of the hydroxyl radical (OH), hydrogen peroxide (H(2) O(2) ); endogenous ABA and malondialdehyde (MDA). The highest H(2) O(2) and MDA content was found in PEG treated groups of both genotypes, but with more in aba2-1. ABA treatment under stress reduced the accumulation of H(2) O(2) and MDA, while it promoted activity of SOD, CAT and APX. APX activity was higher than CAT activity in ABA-treated WT and aba2-1, indicating a protective role of APX rather than CAT during osmotic stress-induced oxidative damage. Treatment with ABA also significantly induced increased NOX activity. Oxidative damage was lower in ABA-treated seedlings of both genotypes, which was associated with greater activity of SOD (Mn-SOD1 and 2 and Fe-SOD isoenzymes), CAT and APX in these seedlings after 24 h of stress. These results suggest that osmotic stress effects were overcome by ABA treatment because of increased SOD, CAT, APX and NOX. PMID- 21973088 TI - OsARF12, a transcription activator on auxin response gene, regulates root elongation and affects iron accumulation in rice (Oryza sativa). AB - * Auxin has an important role in maintaining optimal root system architecture (RSA) that can cope with growth reductions of crops caused by water or nutrient shortages. However, the mechanism of controlling RSA remains largely unclear. Here, we found a limiting factor of RSA--OsARF12--an auxin response factor whose knockout led to decreased primary root length in rice (Oryza sativa). * OsARF12 as a transcription activator can facilitate the expression of the auxin response element DR5::GFP, and OsARF12 was inhibited by osa-miRNA167d by transient expression in tobacco and rice callus. * The root elongation zones of osarf12 and osarf12/25, which had lower auxin concentrations, were distinctly shorter than for the wild-type, possibly as a result of decreased expression of auxin synthesis genes OsYUCCAs and auxin efflux carriers OsPINs and OsPGPs. The knockout of OsARF12 also altered the abundance of mitochondrial iron-regulated (OsMIR), iron (Fe)-regulated transporter1 (OsIRT1) and short postembryonic root1 (OsSPR1) in roots of rice, and resulted in lower Fe content. * The data provide evidence for the biological function of OsARF12, which is implicated in regulating root elongation. Our investigation contributes a novel insight for uncovering regulation of RSA and the relationship between auxin response and Fe acquisition. PMID- 21973089 TI - Quantitative real-time PCR and the (1->3)-beta-D-glucan assay for differentiation between Pneumocystis jirovecii pneumonia and colonization. AB - We evaluated whether quantitative PCR (qPCR) and (1 -> 3)-beta-d-glucan assays could be used to differentiate Pneumocystis pneumonia (PCP) from Pneumocystis jirovecii colonization in immunocompromised patients with pulmonary infiltrates. A total of 40 bronchoalveolar lavage samples and 107 induced sputum samples from 147 patients who were suspected of having PCP were obtained for PCR detection of P. jirovecii. Diagnoses of definite PCP, probable PCP, pneumonia with P. jirovecii colonization (colonization) and pneumonia without colonization (non colonization) were made in 11, 42, 15 and 60 patients, respectively. A PCP diagnosis was undetermined in 19 patients. The copy numbers, determined using qPCR, were significantly higher in definite PCP and probable PCP patients than in colonized patients. The area under the receiver-operating characteristic curve (AUC), sensitivity and specificity for discriminating definite PCP from colonization were 0.96, 100.0% and 80.0%, respectively, at a cut-off value of 1300 copies/mL. The values for discriminating probable PCP from colonization were 0.71, 66.7% and 73.3%, respectively, at a cut-off value of 340 copies/mL. beta-d glucan levels were significantly higher in patients with both definite PCP and probable PCP than in colonized patients. The AUC, sensitivity and specificity for discriminating definite PCP were 0.91, 100.0% and 80.0%, respectively, at a cut off value of 15.6 pg/mL. The values for discriminating probable PCP were 0.78, 76.2% and 73.3%, respectively, at a cut-off value of 6.0 pg/mL. Both qPCR and the beta-d-glucan assay displayed high accuracy for discriminating colonization from definite PCP and displayed moderate accuracy for discriminating colonization from probable PCP. PMID- 21973091 TI - Targeted drug therapy: the platelet side. AB - Targeted therapy is certainly considered the future of cancer treatment. Several new molecules targeting critical intracellular signaling actors, particularly kinases, are arriving in clinics and many other are under development. However, proteins targeted by these drugs are common to many cell types and are particularly implicated in the highly dynamic processes of platelet activation. Therefore, the effects of targeted drugs, including kinase inhibitors, on platelet activation have to be considered in clinical practice. Moreover, their analysis also represents an opportunity to increase our knowledge in platelet biology and physiology and to develop novel antiplatelet strategies. In this review we briefly describe the major platelet signaling pathways that may be affected by these new drugs and discuss some clinical implications of their use. PMID- 21973092 TI - Bootstrap standard error and confidence intervals for the correlations corrected for indirect range restriction. AB - The standard Pearson correlation coefficient, r, is a biased estimator of the population correlation coefficient, rho(XY) , when predictor X and criterion Y are indirectly range-restricted by a third variable Z (or S). Two correction algorithms, Thorndike's (1949) Case III, and Schmidt, Oh, and Le's (2006) Case IV, have been proposed to correct for the bias. However, to our knowledge, the two algorithms did not provide a procedure to estimate the associated standard error and confidence intervals. This paper suggests using the bootstrap procedure as an alternative. Two Monte Carlo simulations were conducted to systematically evaluate the empirical performance of the proposed bootstrap procedure. The results indicated that the bootstrap standard error and confidence intervals were generally accurate across simulation conditions (e.g., selection ratio, sample size). The proposed bootstrap procedure can provide a useful alternative for the estimation of the standard error and confidence intervals for the correlation corrected for indirect range restriction. PMID- 21973093 TI - A simple and effective decision rule for choosing a significance test to protect against non-normality. AB - There is no formal and generally accepted procedure for choosing an appropriate significance test for sample data when the assumption of normality is doubtful. Various tests of normality that have been proposed over the years have been found to have limited usefulness, and sometimes a preliminary test makes the situation worse. The present paper investigates a specific and easily applied rule for choosing between a parametric and non-parametric test, the Student t test and the Wilcoxon-Mann-Whitney test, that does not require a preliminary significance test of normality. Simulations reveal that the rule, which can be applied to sample data automatically by computer software, protects the Type I error rate and increases power for various sample sizes, significance levels, and non-normal distribution shapes. Limitations of the procedure in the case of heterogeneity of variance are discussed. PMID- 21973094 TI - A closer look at the effect of preliminary goodness-of-fit testing for normality for the one-sample t-test. AB - Student's one-sample t-test is a commonly used method when inference about the population mean is made. As advocated in textbooks and articles, the assumption of normality is often checked by a preliminary goodness-of-fit (GOF) test. In a paper recently published by Schucany and Ng it was shown that, for the uniform distribution, screening of samples by a pretest for normality leads to a more conservative conditional Type I error rate than application of the one-sample t test without preliminary GOF test. In contrast, for the exponential distribution, the conditional level is even more elevated than the Type I error rate of the t test without pretest. We examine the reasons behind these characteristics. In a simulation study, samples drawn from the exponential, lognormal, uniform, Student's t-distribution with 2 degrees of freedom (t(2) ) and the standard normal distribution that had passed normality screening, as well as the ingredients of the test statistics calculated from these samples, are investigated. For non-normal distributions, we found that preliminary testing for normality may change the distribution of means and standard deviations of the selected samples as well as the correlation between them (if the underlying distribution is non-symmetric), thus leading to altered distributions of the resulting test statistics. It is shown that for skewed distributions the excess in Type I error rate may be even more pronounced when testing one-sided hypotheses. PMID- 21973095 TI - Scale validity evaluation with congeneric measures in hierarchical designs. AB - A procedure for validity estimation of multi-component measuring instruments in hierarchical designs is outlined. The method is developed within the framework of the popular latent variable modelling methodology. The approach is readily applicable for examining interrelationship indices between composite sum scores and criterion variables in two-level studies. The procedure is also useful for obtaining estimates and confidence intervals of criterion validity coefficients during the process of scale construction and development with hierarchical data. The method is illustrated with an empirical example. PMID- 21973096 TI - Clarifying the role of mean centring in multicollinearity of interaction effects. AB - Moderated multiple regression (MMR) is frequently employed to analyse interaction effects between continuous predictor variables. The procedure of mean centring is commonly recommended to mitigate the potential threat of multicollinearity between predictor variables and the constructed cross-product term. Also, centring does typically provide more straightforward interpretation of the lower order terms. This paper attempts to clarify two methodological issues of potential confusion. First, the positive and negative effects of mean centring on multicollinearity diagnostics are explored. It is illustrated that the mean centring method is, depending on the characteristics of the data, capable of either increasing or decreasing various measures of multicollinearity. Second, the exact reason why mean centring does not affect the detection of interaction effects is given. The explication shows the symmetrical influence of mean centring on the corrected sum of squares and variance inflation factor of the product variable while maintaining the equivalence between the two residual sums of squares for the regression of the product term on the two predictor variables. Thus the resulting test statistic remains unchanged regardless of the obvious modification of multicollinearity with mean centring. These findings provide a clear understanding and demonstration on the diverse impact of mean centring in MMR applications. PMID- 21973097 TI - Plausible measurement analogies to some psychometric models of test performance. AB - Psychometricians hypothesize that cognitive abilities such as reading, writing and spelling are measurable. However, they prefer to model item response probabilities than to study the internal structure of cognitive attributes. The theory of conjoint measurement, via its unique capacity to detect the quantitative structure of non-extensive attributes, can be used for the latter purpose. It is shown that conjoint systems analogous to the numerical composition rules advanced by the Rasch, many facet Rasch and two-parameter logistic models can be formulated using well-established axioms, representation theorems and proofs. Examples using empirical and synthetic data are presented. It was concluded that the lack of descriptive, behavioural theory remains the biggest obstacle to the scientific measurement of cognitive abilities. PMID- 21973098 TI - Constructing bootstrap confidence intervals for principal component loadings in the presence of missing data: a multiple-imputation approach. AB - Earlier research has shown that bootstrap confidence intervals from principal component loadings give a good coverage of the population loadings. However, this only applies to complete data. When data are incomplete, missing data have to be handled before analysing the data. Multiple imputation may be used for this purpose. The question is how bootstrap confidence intervals for principal component loadings should be corrected for multiply imputed data. In this paper, several solutions are proposed. Simulations show that the proposed corrections for multiply imputed data give a good coverage of the population loadings in various situations. PMID- 21973099 TI - Using SAS PROC TCALIS for multigroup structural equation modelling with mean structures. AB - Multigroup structural equation modelling (SEM) is a technique frequently used to evaluate measurement invariance in social and behavioural science research. Before version 9.2, SAS was incapable of handling multigroup SEM. However, this limitation is resolved in PROC TCALIS in SAS 9.2. For the purpose of illustration, this paper provides a step-by-step guide to programming the tests of measurement invariance and partial invariance using PROC TCALIS for multigroup SEM with mean structures. Fit indices and parameter estimates are validated, thus providing an alternative tool for researchers conducting both applied and simulated studies. Other new features (e.g., different types of modelling languages and estimation methods) and limitations (e.g., ordered-categorical SEM and multilevel SEM) of the TCALIS procedure are also briefly discussed. PMID- 21973100 TI - Antiradical properties of red wine portisins. AB - The free radical chemistry of two polyphenolic pigments from red wine, belonging to the family of portisins, has been investigated after reaction with O(2)(*-) radicals using electron paramagnetic resonance (EPR) spectroscopy. Two portisins derived from malvidin-3-glucoside and cyanidin-3-glucoside were used for this study. Stable free radicals were detected with both portisins and correspond to unpaired electrons localized on the B as well as F rings of the portisins. Interpretations were confirmed by comparison with the spectra of free radicals formed by oxidation of the model compounds cyanidin-3-glucoside, malvidin-3 glucoside, and catechin. These results concur with previous work reporting the higher antiradical properties of these pigments compared to their anthocyanin precursors. PMID- 21973101 TI - Bioassay-guided isolation of constituents of Piper sarmentosum using a mitochondrial transmembrane potential assay. AB - Bioassay-guided fractionation was conducted on a chloroform-soluble extract of the aerial parts of Piper sarmentosum collected in Vietnam, monitored by a mitochondrial transmembrane potential assay using HT-29 human colon cancer cells. This led to the isolation of four new C-benzylated dihydroflavones, sarmentosumins A-D (1-4), as well as 14 known compounds. The structures of the new compounds were elucidated on the basis of spectroscopic data interpretation. Among these compounds, 1-4 as well as five known C-benzylated dihydroflavones (5 9) and a piperamide, pipercallosine (11), were found to induce apoptosis in HT-29 cells by moderately reducing the mitochondrial transmembrane potential (DeltaPsim), with ED50 values ranging from 1.6 to 13.6 MUM. Furthermore, 7 methoxydichamanetin (8) and pinocembrin (10) exhibited proteasome inhibitory activities in a human 20S proteasome bioassay with IC50 values of 3.45+/-0.18 and 2.87+/-0.26 MUM, respectively. This is the first time that C-benzylated dihydroflavones have been reported to demonstrate an apoptotic effect associated with disruption of the mitochondrial transmembrane potential. PMID- 21973102 TI - Comparison between the SCL-90-R and MMPI in TMD patients with psychological problems. AB - OBJECTIVE: The aim of the study was to investigate the relationships between the Symptom Checklist-90-Revision (SCL-90-R) and the Minnesota Multiphasic Personality Inventory (MMPI) in temporomandibular disorders (TMD) patients with psychological problems. MATERIALS AND METHODS: Subjective symptoms, objective signs, and psychological characteristics of 36 TMD patients with psychological problems were analyzed. The symptom severity index (SSI) and craniomandibular index (CMI) were used to assess subjective symptoms and objective signs of patients with TMD, respectively. The SCL-90-R and MMPI were used for psychological evaluation. RESULTS: The SSI was not significantly correlated with the CMI in TMD patients with psychological problems, and these indices displayed significant correlations with the SCL-90-R and MMPI in several selected subscales. The results of SCL-90-R had a limited relationship with those of MMPI in these patients. Based on the MMPI diagnosis, the SCL-90-R somatization subscale showed moderate to high sensitivity and specificity, but the SCL-90-R depression subscale showed moderate to low sensitivity and specificity. CONCLUSIONS: Considering the limited relationship between the SCL-90-R and MMPI in TMD patients with psychological problems, more comprehensive psychological tests are recommended when clinicians suspect patients with TMD of having accompanying psychological problems. PMID- 21973103 TI - Faster decline of physical performance in older adults with higher levels of baseline locomotive function. AB - AIM: The purpose of this longitudinal study was to determine whether the rate of decline in community-dwelling older adults varies according to baseline locomotive function levels. METHODS: This longitudinal study was conducted in community-dwelling older adults in Kyoto, Japan. In addition to information about falls, physical performance was assessed using a series of tests, including 10-m walking time, timed up and go (TUG) test, functional reach, one-leg stand test, and five chair stand test. The outcomes for each patient were measured once in 2009 and then followed up 1 year later. The change in physical performance was then determined. We divided the participants into tertiles (T1, T2, and T3) according to timed up and go test results, and the differences among the three groups were compared. RESULTS: Of the 252 individuals who were enrolled in the study, 231 (91.6%) completed the 12-month follow-up: 77 in the T1 group; 78 in the T2 group; and 76 in the T3 group. The T1 group showed a significantly larger decrease than the T2 and T3 groups in the 10-m walking time and TUG tests (P < 0.05). However, there were no significant differences in functional reach, one leg standing test, or five chair stand test among the three groups. In the T1 group, the number of falls and elderly who had developed fear of falling increased during the study period. CONCLUSIONS: This study demonstrated that elderly with the highest baseline performances were more likely to show a greater decline in locomotive performance than the other groups. Further study is required to elucidate the mechanism of faster physical functional decline in robust elderly. PMID- 21973104 TI - The diagnostic performance of allergen-molecules in comparison to allergen extracts. AB - BACKGROUND: This study evaluated the diagnostic performance of naturally purified allergen-molecules compared to that of allergen-extracts for house dust mite, cat dander epithelium and dog dander. METHODS: In vitro tests for allergen-specific IgE were performed on the IMMULITE((r)) 2000 in serum samples from 66 allergic patients. RESULTS: House dust mite: specificity for the allergen-extract (D1) and the allergen-molecules (nDer p 1, nDer f 1, nDer p 2 and nDer f 2) is comparable. The allergen-extract has a significantly higher sensitivity (100%) and total agreement (TA) (93%) relative to sensitivity (57%-70%) and TA (76%-81%) of the individual allergen-molecules. Cat dander epithelium: sensitivity (90%), specificity (96%) and TA (94%) of the allergen-molecule (nFel d 1) are comparable to those of the allergen-extract (E1). Dog dander: The allergen-molecule (nCan d 1) and allergen-extract (E5) have comparable specificity and TA. The allergen extract has a lower sensitivity (52%) than the allergen-molecule (71%), although not significant (p=0.125). CONCLUSIONS: There is no diagnostic benefit of using allergen-molecules instead of allergen-extracts for initial allergy screening on cat dander epithelium and dog dander. However, use of these allergen-molecules might contribute to better standardization of the specific IgE tests. The studied allergen-molecules for house dust mite are of minor diagnostic value, because of loss of sensitivity. PMID- 21973105 TI - Establishing high resolution melting analysis: method validation and evaluation for c-RET proto-oncogene mutation screening. AB - BACKGROUND: Reliable and effective primary screening of mutation carriers is the key condition for common diagnostic use. The objective of this study is to validate the method high resolution melting (HRM) analysis for routine primary mutation screening and accomplish its optimization, evaluation and validation. Due to their heterozygous nature, germline point mutations of c-RET proto oncogene, associated to multiple endocrine neoplasia type 2 (MEN2), are suitable for HRM analysis. Early identification of mutation carriers has a major impact on patients' survival due to early onset of medullary thyroid carcinoma (MTC) and resistance to conventional therapy. METHODS: The authors performed a series of validation assays according to International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines for validation of analytical procedures, along with appropriate design and optimization experiments. After validated evaluation of HRM, the method was utilized for primary screening of 28 pathogenic c-RET mutations distributed among nine exons of c-RET gene. RESULTS: Validation experiments confirm the repeatability, robustness, accuracy and reproducibility of HRM. All c-RET gene pathogenic variants were detected with no occurrence of false-positive/false negative results. CONCLUSIONS: The data provide basic information about design, establishment and validation of HRM for primary screening of genetic variants in order to distinguish heterozygous point mutation carriers among the wild-type sequence carriers. HRM analysis is a powerful and reliable tool for rapid and cost-effective primary screening, e.g., of c-RET gene germline and/or sporadic mutations and can be used as a first line potential diagnostic tool. PMID- 21973106 TI - Gold nanoparticles in the clinical laboratory: principles of preparation and applications. AB - In order to meet the challenges of effective healthcare, the clinical laboratory is constantly striving to improve testing sensitivity while reducing the required time and cost. Gold nanoparticles (AuNPs) are proposed as one of the most promising tools to meet such goals. They have unique optophysical properties which enable sensitive detection of biomarkers, and are easily amenable to modification for use in different assay formats including immunoassays and molecular assays. Additionally, their preparation is relatively simple and their detection methods are quite versatile. AuNPs are showing substantial promise for effective practical applications and commercial utilization is already underway. This article covers the principles of preparation of AuNPs and their use for development of different diagnostic platforms. PMID- 21973107 TI - Ultra-sensitive troponin I levels to exclude acute myocardial infarction from myocardial injury. AB - BACKGROUND: Third generation troponin assays should aid in the rule-out of acute myocardial infarction (AMI). The study aim was to assess the capability of admission measurement of ultra-sensitive troponin I (TnI-Ultra) to exclude AMI from other myocardial injury. METHODS: The first TnI-Ultra sample from 856 patients at presentation to the Emergency Department and subsequent admission to the Cardiac Care Unit were considered in this case series. Myoglobin was simultaneously detected in 684 patients. RESULTS: The sensitivity of the first single TnI-Ultra level was 82.5% in overall AMI, and similar in ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI), admitted, respectively at 3 and 8 h from symptoms. The diagnostic capability of a first single TnI-Ultra level was poor for both STEMI and NSTEMI to discriminate and rule-out overall AMI from myocardial injury, with an area under the receiver-operating curve of 0.65 and a negative likelihood ratio of 0.55. Adopting an optimal test threshold or adding myoglobin detection did not improve TnI-Ultra performances. CONCLUSIONS: The capability of a first single TnI Ultra level to exclude AMI from other myocardial injury in early and late presenters is poor. Addition of myoglobin assay offered no further improvement and was not considered useful. PMID- 21973108 TI - Reactive oxygen species are involved in pollen tube initiation in kiwifruit. AB - The role of reactive oxygen species (ROS) during pollen tube growth has been well established, but its involvement in the early germination stage is poorly understood. ROS production has been reported in germinating tobacco pollen, but evidence for a clear correlation between ROS and germination success remains elusive. Here, we show that ROS are involved in germination and pollen tube formation in kiwifruit. Using labelling with dihydrofluorescein diacetate (H(2) FDA) and nitroblue tetrazolium (NBT), endogenous ROS were detected immediately following pollen rehydration and during the lag phase preceding pollen tube emergence. Furthermore, extracellular H(2) O(2) was found to accumulate, beginning a few minutes after pollen suspension in liquid medium. ROS production was essential for kiwifruit pollen performance, since in the presence of compounds acting as superoxide dismutase/catalase mimic (Mn-5,10,15,20-tetrakis(1 methyl-4-pyridyl)21H,23H-porphin, Mn-TMPP) or as NADPH oxidase inhibitor (diphenyleneiodonium chloride, DPI), ROS levels were reduced and pollen tube emergence was severely or completely inhibited. Moreover, ROS production was substantially decreased in the absence of calcium, and by chromium and bisphenol A, which inhibit germination in kiwifruit. Peroxidase activity was cytochemically revealed after rehydration and during germination. In parallel, superoxide dismutase enzymes, particularly the Cu/Zn-dependent subtype - which function as superoxide radical scavengers - were detected by immunoblotting and by an in-gel activity assay in kiwifruit pollen, suggesting that ROS levels may be tightly regulated. Timing of ROS appearance, early localisation at the germination aperture and strict requirement for germination clearly suggest an important role for ROS in pollen grain activation and pollen tube initiation. PMID- 21973109 TI - The prevalence and correlates of depressive symptoms among adolescent mothers: results from a 17-year longitudinal study. AB - The objective of the authors in this study was to examine the prevalence and correlates of elevated depressive symptoms in a 17-year cohort study of 173 women who were unmarried, pregnant adolescents between June 1988 and January 1990. Multiple logistic regression was used to estimate the associations between correlates and elevated depressive symptoms during five distinct developmental periods of the life course. Depressive symptoms were measured by the Brief Symptom Inventory depression subscale. The prevalence of elevated depressive symptoms in adolescent mothers significantly increased over the 17 years of the study from 19.8% to 35.2%. In adjusted analyses, antenatal depressive symptoms were positively and significantly associated with elevated depressive symptoms at every developmental period. Intimate partner violence was positively and significantly associated with elevated depressive symptoms during all but one developmental period. Other significant correlates of elevated depressive symptoms included welfare receipt, smoking, and parity, all of which were significant at some, but not other, developmental periods. Antenatal depressive symptoms and intimate partner violence were positively and significantly associated with elevated depressive symptoms. Given the public health consequences associated with maternal depression, clinical and community-based interventions should be developed to identify and to treat adolescent mothers at risk for antenatal depression and intimate partner violence. PMID- 21973110 TI - The impact of structured support groups for pregnant South African women recently diagnosed HIV positive. AB - The authors of this study evaluated a structured 10-session psychosocial support group intervention for newly HIV-diagnosed pregnant South African women. Participants were expected to display increases in HIV disclosure, self-esteem, active coping and positive social support, and decreases in depression, avoidant coping, and negative social support. Three hundred sixty-one pregnant HIV infected women were recruited from four antenatal clinics in Tshwane townships from April 2005 to September 2006. Using a quasi-experimental design, assessments were conducted at baseline and two and eight months post-intervention. A series of random effects regression analyses were conducted, with the three assessment points treated as a random effect of time. At both follow-ups, the rate of disclosure in the intervention group was significantly higher than that of the comparison group (p<0.001). Compared to the comparison group at the first follow up, the intervention group displayed higher levels of active coping (t=2.68, p<0.05) and lower levels of avoidant coping (t=-2.02, p<0.05), and those who attended at least half of the intervention sessions exhibited improved self esteem (t=2.11, p<0.05). Group interventions tailored for newly HIV positive pregnant women, implemented in resource-limited settings, may accelerate the process of adjusting to one's HIV status, but may not have sustainable benefits over time. PMID- 21973111 TI - Women's walking program for African American women: expectations and recommendations from participants as experts. AB - Effective interventions that increase adherence to physical activity are important for African American women because generally they are less active and more obese compared to white American women. The purpose of the authors in this study was to elicit from women who began a 12-month physical activity program between 2002 and 2005: (1) their recollections of outcome expectations and barriers, (2) feedback on program components, and (3) suggestions for program change. In 2007, the authors conducted qualitative post-intervention focus group interviews with women who had participated in the enhanced treatment group. Thirty-three African American women aged 44-69 years at the time of the study participated in one of four focus groups held at their community intervention site. Focus groups were formed on the basis of low (walked<50% of expected walks) versus high (walked>=50% of expected walks) adherence and low (0-2) versus high (3-4) attendance at the four workshops held during the 6-month adoption phase. Audio-taped sessions were transcribed, coded independently, and then uploaded into NVivo7 for final coding and data analysis. Suggestions for future program components include a lifestyle physical activity prescription, pedometers for self-monitoring, ongoing group support, and automated telephone support. Focus group participants can serve as experts to assist in content development for improving program effectiveness. PMID- 21973112 TI - Determinants of perceived sexism and their role on the association of sexism with mental health. AB - The authors of this study sought to compare the socioeconomic factors related to perceived sexism in employed and non-employed Spanish women and to examine whether the relationship of perceived sexism with mental health outcomes is reduced when such factors are taken into account. Data were taken from the 2006 Spanish Health Survey, including women aged 20-64 years (n=10,927). Multivariate logistic regression models were used to analyze the independent relationships between socioeconomic variables and perceived sexism and also between perceived sexism and poor mental health. In this latter case, socioeconomic variables were included by blocks in the logistic models. Perceived sexism was higher among employed women (3.9% vs. 2.8% among non-employed) and mainly among those in a managerial position (11.35%; adjusted OR: 2.71, 95% CI: 1.30-5.67) and having irregular working hours (5.5%; adjusted OR: 1.60, 95% CI: 1.10-2.34). Socioeconomic and family characteristics were associated with perceived sexism among women. Perceived sexism was associated with poor mental health, and this remained the case when different independent variables were taken into account. These results highlight the importance of taking into account gender discrimination in different aspects of our society, such as work and family organization, and in planning mental health interventions. PMID- 21973113 TI - Personal growth in mothers: examination of the suitability of the posttraumatic growth inventory as a measurement tool. AB - The validity of the Posttraumatic Growth Inventory for the experience of motherhood was examined in three separate studies, conducted in Israel between 2008 and 2010. Study 1 (n=150) compared the answers of new first-time mothers to an open-ended question regarding changes following childbirth with the Posttraumatic Growth Inventory dimensions. Study 2 replicated this procedure using a more diverse sample (n=157) to confirm the usefulness of the Posttraumatic Growth Inventory among various sub-groups of mothers (first-time and non-first-time mothers, mothers of twins and singletons, mothers of pre-term and full-term infants). Study 3 (n=152 mothers and their own mothers) sought to corroborate mothers' scores on the Posttraumatic Growth Inventory by means of their own mothers' reports of their daughters' growth following childbirth. This study also examined the applicability of the Posttraumatic Growth Inventory's five factor structure-new possibilities, relating to others, personal strength, spiritual change, and appreciation of life-to the population of mothers. The findings indicated that the Posttraumatic Growth Inventory is indeed an effective instrument for the measurement of mothers' perceived positive changes following childbirth, and can be used for this purpose at least for several years after the birth. PMID- 21973114 TI - gamma-Tocotrienol inhibits HGF-dependent mitogenesis and Met activation in highly malignant mammary tumour cells. AB - OBJECTIVES: Aberrant Met signalling is associated with aggressive cancer cell phenotypes. gamma-tocotrienol displays potent anti-cancer activity that is associated with suppression of HER/ErbB receptor signalling. Experiments were conducted to investigate the effects of gamma-tocotrienol treatment on HGF dependent +SA mammary tumour cell proliferation, upon Met activation. MATERIALS AND METHODS: The +SA cells were maintained in serum-free defined media containing 10 ng/ml HGF as the mitogen. Cell viability was determined using the MTT assay, western blot analysis was used to measure protein expression, and Met expression and activation were determined using immunofluorescent staining. RESULTS AND CONCLUSIONS: Treatment with gamma-tocotrienol or Met inhibitor, SU11274, significantly inhibited HGF-dependent +SA cell replication in a dose responsive manner. Treatment with 4 MUmgamma-tocotrienol reduced both total Met levels and HGF-induced Met autophosphorylation. In contrast, similar treatment with 5.5 MUm SU11274 inhibited HGF-induced Met autophosphorylation, but had no effect on total Met levels. Combined treatment with subeffective doses of gamma tocotrienol (2 MUm) and SU11274 (3 MUm) resulted in significant inhibition of +SA cell expansion compared to treatment with individual agents alone. These findings show, for the first time, the inhibitory effects of gamma-tocotrienol on Met expression and activation, and strongly suggest that gamma-tocotrienol treatment may provide significant health benefits in prevention and/or treatment of breast cancer, in women with deregulated HGF/Met signalling. PMID- 21973115 TI - Evaluation of the permeability of agricultural films to various fumigants. AB - A variety of agricultural films are commercially available for managing emissions and enhancing pest control during soil fumigation. These films are manufactured using different materials and processes which can ultimately result in different permeability to fumigants. A systematic laboratory study of the permeability of the agricultural films to nine fumigants was conducted to evaluate the performance of commonly used film products, including polyethylene, metalized, and high-barrier films. The permeability, as expressed by mass transfer coefficient (cm/h), of 27 different films from 13 manufacturers ranged from below 1 * 10(-4) cm/h to above 10 cm/h at 25 degrees C under ambient relative humidity test conditions. The wide range in permeability of commercially available films demonstrates the need to use films which are appropriate for the fumigation application. The effects of environmental factors, such as temperature and humidity, on the film permeability were also investigated. It was found that high relative humidity could drastically increase the permeability of the high-barrier films. The permeability of some high-barrier films was increased by 2-3 orders of magnitude when the films were tested at high relative humidity. Increasing the temperature from 25 to 40 degrees C increased the permeability for some high barrier films up to 10 times more than the permeability at 25 degrees C, although the effect was minimal for several of these films. Analysis of the distribution of the permeability of the films under ambient humidity conditions to nine fumigants indicated that the 27 films largely followed the material type, although the permeability varied considerably among the films of similar material. PMID- 21973116 TI - Leptin and the regulation of endothelial function in physiological and pathological conditions. AB - Obesity and the accompanying metabolic syndrome are among the most important causes of cardiovascular pathologies associated with endothelial dysfunction, such as arterial hypertension and atherosclerosis. This detrimental effect of obesity is mediated, in part, by excessive production of the adipose tissue hormone leptin. Under physiological conditions leptin induces endothelium dependent vasorelaxation by stimulating nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). Leptin activates endothelial NO synthase (eNOS) through a mechanism involving AMP-activated protein kinase (AMPK) and protein kinase B/Akt, which phosphorylates eNOS at Ser(1177) , increasing its activity. Under pathological conditions, such as obesity and metabolic syndrome, the NO mediated vasodilatory effect of leptin is impaired. Resistance to the acute NO mimetic effect of leptin is accounted for by chronic hyperleptinaemia and may result from different mechanisms, such as downregulation of leptin receptors, increased levels of circulating C-reactive protein, oxidative stress and overexpression of suppressor of cytokine signalling-3. In short-lasting obesity, impaired leptin-induced NO production is compensated by EDHF; however, in advanced metabolic syndrome, the contribution of EDHF to the haemodynamic effect of leptin becomes inefficient. Resistance to the vasodilatory effects of leptin may contribute to the development of arterial hypertension owing to unopposed stimulation of the sympathetic nervous system by this hormone. PMID- 21973117 TI - Sensitivity and specificity of Munro microabscess detected by reflectance confocal microscopy in the diagnosis of psoriasis vulgaris. PMID- 21973118 TI - Barriers toward epilepsy surgery. A survey among practicing neurologists. AB - PURPOSE: Guidelines for refractory epilepsy recommend timely referral of potential surgical candidates to an epilepsy center for evaluation. However, this approach is seldom a priority for treating neurologists, possibly because of inertia of previous practice and personal attitudes, leading to a buildup of psychosocial disabilities and increased risk of morbidity and mortality. The aim of this study was to assess knowledge and attitudes toward epilepsy surgery among practicing neurologists and identify the barriers that delay the treatment. METHODS: We surveyed 183 Italian adult and child neurologists with an ad hoc questionnaire exploring physicians' willingness to refer patients for epilepsy surgery when such treatment may be indicated. Thirteen of 14 questions had graded answers ranging from 1 (unfavorable to surgery) to 10 (favorable). We compared the overall scores and per-question scores of the neurologists versus a group of academic and clinical leaders in the field. KEY FINDINGS: The neurologists gave responses characterized by extreme variability (i.e., wide response interquartile range) around intermediate scores. Experts had higher and less variable scores favoring surgery. The two groups differed significantly on issues such as how long to pursue pharmacologic treatment and information about indications and outcome of surgery. Multivariate analysis indicated that neurologists' attitudes correlated with the number of patients referred for surgery (p < 0.01) and the geographical region where specialty was attained (p < 0.01). Other variables such as years in practice, number of patients treated for epilepsy, or type of specialty had no predictive value on physicians' behavior. SIGNIFICANCE: The majority of Italian neurologists have highly variable attitudes toward epilepsy surgery, reflecting ambivalence and uncertainty toward this type of treatment. About two thirds of responders are nonaligned with the opinion leaders, mainly due to differences in handling pharmacologic treatment and information regarding epilepsy surgery, which affect their attitudes and ultimately patient management. Strategies that may solve the lack of agreement include reinforcing the concept of pharmacoresistance and associated risks, as opposed to the safety and potential benefits of surgery, the use of epilepsy quality measures during follow up, and the adoption of structured referral sheets and greater involvement of patients in decision making. These measures should facilitate the referral of potential candidates for surgical evaluation and improve overall quality of care. PMID- 21973119 TI - Prevalence, severity and clinical features of psoriasis in fingernails and toenails in adult patients: Italian experience. AB - BACKGROUND: Psoriasis is a chronic inflammatory skin disease affecting 2.0-6.5% of the European population. Although the most striking clinical features of psoriasis involve the skin, other organs including nails and joints may be affected in a substantial proportion of patients. Literature reports nail involvement in 10-56% of psoriatic patients, with common physical and social impairment. However, the precise prevalence of specific clinical features of nail psoriasis is somewhat under-reported. OBJECTIVES: Our cross-sectional study aimed at describing the prevalence and the clinical features of nail involvement in adult psoriatic patients in a psoriasis referral centre in northern Italy. METHODS: A total of 178 (124 men, 54 women) consecutive adult patients (>=18 years old) with psoriasis were included. Psoriasis Area and Severity Index (PASI) and Nail Psoriasis Severity Index (NAPSI) scores were calculated for each patient. Relevant medical history was recorded. RESULTS: Nail involvement was present in 137 (99 men, 38 women) patients (76.9%). The most common nail abnormality was onycholysis, followed by crumbling, subungual hyperkeratosis, pitting and discoloration. Pitting and onycholysis were the most prevalent patterns observed in fingernails, whereas onycholysis and crumbling were the most frequent changes detected in toenails. The most frequently and severely affected nails were the fourth fingernail and the first toenail. The average PASI score was higher in individuals with nail involvement (12.0 vs. 8.7, P = 0.06). Nail changes were present in 85.7% of patients with psoriatic arthritis. CONCLUSIONS: Our study confirms that nail involvement may be overlooked in psoriasis patients. Different psoriatic patterns in the nail affect specific digits more frequently. PMID- 21973120 TI - Mechanistic investigation and reaction kinetics of the low-pressure copolymerization of cyclohexene oxide and carbon dioxide catalyzed by a dizinc complex. AB - The reaction kinetics of the copolymerization of carbon dioxide and cyclohexene oxide to produce poly(cyclohexene carbonate), catalyzed by a dizinc acetate complex, is studied by in situ attenuated total reflectance infrared (ATR-IR) and proton nuclear magnetic resonance ((1)H NMR) spectroscopy. A parameter study, including reactant and catalyst concentration and carbon dioxide pressure, reveals zero reaction order in carbon dioxide concentration, for pressures between 1 and 40 bar and temperatures up to 80 degrees C, and a first-order dependence on catalyst concentration and concentration of cyclohexene oxide. The activation energies for the formation of poly(cyclohexene carbonate) and the cyclic side product cyclohexene carbonate are calculated, by determining the rate coefficients over a temperature range between 65 and 90 degrees C and using Arrhenius plots, to be 96.8 +/- 1.6 kJ mol(-1) (23.1 kcal mol(-1)) and 137.5 +/- 6.4 kJ mol(-1) (32.9 kcal mol(-1)), respectively. Gel permeation chromatography (GPC), (1)H NMR spectroscopy, and matrix-assisted laser desorption/ionization time-of-flight (MALDI-ToF) mass spectrometry are employed to study the poly(cyclohexene carbonate) produced, and reveal bimodal molecular weight distributions, with narrow polydispersity indices (<=1.2). In all cases, two molecular weight distributions are observed, the higher value being approximately double the molecular weight of the lower value; this finding is seemingly independent of copolymerization conversion or reaction parameters. The copolymer characterization data and additional experiments in which chain transfer agents are added to copolymerization experiments indicate that rapid chain transfer reactions occur and allow an explanation for the observed bimodal molecular weight distributions. The spectroscopic and kinetic analyses enable a mechanism to be proposed for both the copolymerization reaction and possible side reactions; a dinuclear copolymerization active site is implicated. PMID- 21973121 TI - What is the proximate cause for size-dependent ecophysiological differences in vascular epiphytes? AB - Size-related variation in physiological parameters as diverse as photosynthetic capacity, abscisic acid relationships or the relative water deficit at stomatal closure have been reported for a large number of vascular epiphytes, but the proximate mechanism behind these observations has not been identified. We test four possible reasons for size-related changes in photosynthetic capacity, leaf-N content and specific leaf area: (i) plant size itself, (ii) plant age or developmental stage, (iii) previous nutrition, or (iv) previous water regime. A suite of study species and approaches were used: a 'natural experiment' with the orchid Polystachya foliosa; an experimental field study with another orchid, Dimerandra emarginata; and a study under controlled conditions with the tank bromeliad, Vriesea sanguinolenta. Neither size, age nor differences in water supply caused differences in leaf N and photosynthetic capacity, while low supply of nutrients yielded, and high supply with nutrients completely removed, size related trends. The observed size-related trends are thus a consequence of in situ differences in nutrient acquisition. Arguably, the improved nutrient status of larger plants under natural conditions results from larger tanks, holding moisture for increasingly longer intervals, which allows longer periods of decomposition of detritus and of nutrient uptake. PMID- 21973122 TI - Very slow cooling dynamics of photoexcited carriers in graphene observed by optical-pump terahertz-probe spectroscopy. AB - Using optical-pump terahertz-probe spectroscopy, we study the relaxation dynamics of photoexcited carriers in graphene at different substrate temperatures. We find that at lower temperatures the tail of the relaxation transients measured by the differential probe transmission become slower, extending beyond several hundred picoseconds below 50 K. We interpret the observed relaxation transients as resulting from the cooling of the photoexcited carriers via phonon emission. The slow cooling of the photoexcited carriers at low temperatures is attributed to the bulk of the electron and hole energy distributions moving close enough to the Dirac point that both intraband and interband scattering of carriers via optical phonon emission become inefficient for removing heat from the carriers. Our model, which includes intraband carrier scattering and interband carrier recombination and generation, agrees very well with the experimental observations. PMID- 21973123 TI - Ethylene-induced differential petiole growth in Arabidopsis thaliana involves local microtubule reorientation and cell expansion. AB - * Hyponastic growth is an upward petiole movement induced by plants in response to various external stimuli. It is caused by unequal growth rates between adaxial and abaxial sides of the petiole, which bring rosette leaves to a more vertical position. The volatile hormone ethylene is a key regulator inducing hyponasty in Arabidopsis thaliana. Here, we studied whether ethylene-mediated hyponasty occurs through local stimulation of cell expansion and whether this involves the reorientation of cortical microtubules (CMTs). * To study cell size differences between the two sides of a petiole in ethylene and control conditions, we analyzed epidermal imprints. We studied the involvement of CMT orientation in epidermal cells using the tubulin marker line as well as genetic and pharmacological means of CMT manipulation. * Our results demonstrate that ethylene induces cell expansion at the abaxial side of the- petiole and that this can account for the observed differential growth. At the abaxial side, ethylene induces CMT reorientation from longitudinal to transverse, whereas, at the adaxial side, it has an opposite effect. The inhibition of CMTs disturbed ethylene-induced hyponastic growth. * This work provides evidence that ethylene stimulates cell expansion in a tissue-specific manner and that it is associated with tissue-specific changes in the arrangement of CMTs along the petiole. PMID- 21973124 TI - The impact of raised BMI on the outcome of assisted reproduction: current concepts. AB - Obesity contributes to worse outcomes following treatment using assisted reproductive technology (ART), including lower pregnancy and live birth rates and a higher miscarriage rate. This could be mediated through a detrimental effect on oocyte and embryo quality. Oocyte donation studies have suggested that endometrial changes also play a significant role. Endocrine changes associated with obesity, including hyperandrogenism and insulin resistance, as well as changes in local levels of IGFs, cytokines and leptin are thought to underlie the relationship between raised BMI and adverse ART outcomes. This review aims to highlight these underlying mechanisms. PMID- 21973125 TI - Is ultrasound monitoring of the ovaries during ovulation induction by clomiphene citrate essential? A systematic review. AB - The study objective was to investigate whether ultrasound (US) monitoring is essential during treatment with clomiphene citrate (CC) for ovulation induction, as recommended by the Royal College of Obstetricians and Gynaecologists (RCOG) and the National Institute for Clinical Excellence (NICE). We performed a systematic review of all studies investigating the effects of US in the treatment of ovulatory dysfunction with CC. The main objective of this review was to investigate whether US monitoring during CC treatment reduced multiple pregnancy rates. There was insufficient evidence to suggest that US monitoring reduces multiple pregnancy rates or improves pregnancy rates. On the other hand, no indication that treatment with CC is safe without US monitoring was identified. The small number of relevant studies and the heterogeneity observed in the methodologies of each study prohibit reliable conclusions to be drawn. There is currently no basis for amending the evidence base (good-practice points) used in the RCOG and NICE guidelines, which recommend the use of US to monitor the ovaries during stimulation with CC. PMID- 21973126 TI - Pelvic girdle pain during pregnancy and puerperium. AB - Pelvic girdle pain (PGP) is a term used specifically to pregnancy-related pain in the lumbosacral, sacroiliac and symphysis pubis joints. Pregnancy-induced hormonal and physical changes increase the risk of musculoskeletal problems in pregnancy. The severity of these conditions varies from mild self-limiting pain to a severe disabling condition. PGP is common in pregnancy and while most can be managed as outpatients, a few patients require inpatient admission for further investigations and management. Prompt identification of these conditions is essential to avoid serious disability. Lack of awareness and failure of recognition not only results in women feeling isolated, but may also result in long-term morbidity. In this review, we explore the aetiology, presentation, risk factors, risk of recurrence, differential diagnosis and multidisciplinary management of these conditions. We also enclose obstetric guidelines to increase the awareness of the health professionals. PMID- 21973127 TI - Preventing neural tube defects with folic acid: nearly 20 years on, the majority of women remain unprotected. AB - Many countries, including the USA and Canada, have implemented fortification of foods with folic acid, however the British Government only issues advice that supplements should be taken before and after conceiving. In this study, information was collected from women attending antenatal clinics to understand current levels of compliance with health advice and to investigate what is driving womens' behaviour. Eighty-nine percent of women consumed supplements but only 31% took folic acid prior to conceiving. Hence, the vast majority are starting too late to prevent neural tube defects (NTDs). Educational achievement, income and marital status emerged as the most significant factors influencing non compliance. GPs and midwives were the main catalyst for women starting folic acid, however, 81% of these women started post-conception. When asked why they took folic acid, the majority of women did not mention the association with NTDs. Forty-one percent of women who did not take the supplements at all were unaware that it was recommended that they should. Fortification of UK food products offers a major public health opportunity. In the absence of fortification, gaps in the public health message need to be addressed. GPs and midwives cannot be relied upon alone to educate these women. PMID- 21973128 TI - Pregnancy outcome after 1st-trimester inadvertent exposure to barium sulphate as a contrast media for upper gastrointestinal tract radiography. AB - Despite barium being used as a contrast media for decades, the specific assessment of its safety in pregnant women is scarce. We are reporting the favourable pregnancy outcome in women who were inadvertently exposed to barium swallow and associated ionising radiation, early in pregnancy. A control group of age- and gravidity-matched unexposed pregnant women was also included. There were 32 live-born babies in the exposed group and 94 in the control group. Women had undergone diagnostic upper gastrointestinal tract (UGT) fluoroscopic examination at 3.3 +/- 1.5 weeks' gestation. Estimated maternal radiation dose secondary to barium swallow varied widely, the maximum dose was estimated to be 2.45 mSv. Similar pregnancy outcomes were observed between the groups. The number of babies born with major malformations was not significantly different (p = 1.0) between cases and controls: one (3.1%) vs three (3.2%), respectively. In conclusion, our small prospective cohort study of women suggests no association between inadvertent exposure to ionising radiation and barium sulphate during fluoroscopic barium swallow and adverse fetal outcomes. PMID- 21973129 TI - Interpregnancy BMI change and risk of primary caesarean delivery. AB - We conducted a retrospective study using Missouri maternally linked cohort files (1989-2005). We examined the association between interpregnancy body mass index (BMI) change and risk of primary caesarean delivery. BMI was classified as normal (18.5-24.9 kg/m(2)) or obese (>=30.0 kg/m(2)). Interpregnancy BMI change was defined using the following categories: normal-normal, normal-obese, obese-normal and obese-obese. Logistic regression models were used to generate adjusted odds ratios (OR) and 95% confidence intervals (CI) for the risk of primary caesarean delivery in the second pregnancy. Elevated risks for caesarean delivery in the second pregnancy were noted for normal weight mothers becoming obese (OR = 1.41, 95% CI 1.26-1.57) and obese mothers maintaining their obese status across both pregnancies (OR = 1.75, 95% CI 1.65-1.87). Women with a reduction in BMI (obese normal) had a risk level for primary caesarean section that was comparable with that of women with normal BMI status in both pregnancies. PMID- 21973130 TI - The relationship between body mass index and mid-arm circumference in a pregnant population. AB - Our objective was to correlate body mass index (BMI) with mid-arm circumference (MAC) and also to ascertain whether maternal BMI could be calculated from MAC at booking. We approached all Caucasian women who met the inclusion criteria attending the University College Hospital, London between 1 April 1996 and 30 June 1997 and the Rotunda Hospital, Dublin, Ireland between 15 April 2003 and 19 May 2004. A total of 2,912 women agreed to participate in the research. The participants' maternal height and weight were measured. Their BMI was calculated using the formula: BMI = weight (kg) / height (m(2)). The MAC was measured in cm. Statistical analysis was performed using SPSS for Windows version 11 with p < 0.05 as significant. We found that BMI is directly correlated with MAC (r = 0.836) and estimates of BMI may be calculated from the simple equation BMI = MAC +/- 2. Alternatively, a MAC of >= 27 cm allowed for a detection rate for overweight patients of 75%, with a false positive rate of 15%. PMID- 21973131 TI - Severe heart disease complicating pregnancy does not preclude a favourable pregnancy outcome: 15 years' experience in a single centre. AB - Heart disease (HD) in pregnancy remains a major cause of non-obstetric maternal and neonatal mortality and morbidity. This study describes the outcome in 164 pregnant women with HD (158 deliveries in women in New York Heart Association (NYHA) Classes 1 and 2; 17 in NYHA Classes 3 and 4) who received good antenatal care and benefitted from a specific protocol and experience of a dedicated staff. There were no maternal or neonatal deaths; 46 women were diagnosed peripartum. Based on a sub-division into NYHA categories, and when sub-divided by HD, there were no statistically significant differences between groups with regard to maternal age, gestational age at admission or at delivery, birth weight, 5 min Apgar scores, mode of delivery (caesarean delivery), senior obstetric/anaesthesiology staff in attendance or delivery during day/working hours. There was a higher incidence of pre-term deliveries in women with rheumatic heart disease and Marfan syndrome (p = 0.06) relative to others. Babies of women with coronary heart disease had prolonged postpartum course in the NICU (p = 0.0001) and longer total hospital stays for the mother. In conclusion, well managed, motivated mothers with HD who benefit from comprehensive antenatal care, and are managed primarily by their obstetric and anaesthesia teams, can aspire to a good outcome for themselves and their babies. PMID- 21973132 TI - A meta-analysis of eNOS and ACE gene polymorphisms and risk of pre-eclampsia in women. AB - A meta-analyses of endothelial nitric oxide synthase (eNOS) and angiotensin converting enzyme (ACE) gene polymorphisms in pre-eclampsia was performed. We shortlisted 33 studies (17 for ACE; 16 for eNOS gene polymorphisms), of which 29 articles (16 for ACE and 15 for eNOS) were analysed. Overall, 1,620 cases with pre-eclampsia and 2,158 controls were analysed for intron 16 insertion-deletion polymorphism in ACE gene. A total of 1,610 subjects with pre-eclampsia and 2,875 controls were analysed for the Glu298Asp in eNOS gene. Overall, the random effects odds ratio (OR) with Glu298Asp in eNOS gene was 0.958 (95% confidence intervals, CI 0.747-1.228, p > 0.05), and for the insertion-deletion/ACE polymorphism was 0.987 (95% CI 0.698-1.395, p > 0.05). Significant heterogeneity was observed in the studies that evaluated polymorphisms in ACE (Q value = 55.6; I(2) = 73; p value = 0.000); and eNOS (Q value = 37.2; I(2) = 62.4; p value = 0.001) polymorphisms. No significant risk of pre-eclampsia was observed in both eNOS and ACE genes with these polymorphisms. PMID- 21973133 TI - The relationship of ethnicity, maternal height and shoe size, and method of delivery. AB - In a bid to determine the relationship of ethnicity, maternal height and shoe size as predictors of cephalopelvic disproportion, we conducted a prospective comparative study of primigravidas at term with singleton pregnancies, who had undergone spontaneous labour. A total of 208 primigravidas were studied; 151 (62.9%) achieved vaginal delivery and 57 (37.1%) had emergency caesarean section for failure-to-progress. We found a statistically significant positive correlation between maternal height and vaginal delivery (p = 0.04), but no correlation with maternal shoe size was found (p = 0.24). This study also showed that Caucasian women were significantly more than twice as likely to achieve vaginal delivery compared with Africans (p = 0.02). Maternal height of at least 162.5 cm, has a sensitivity of 74% and a specificity of 43% for predicting vaginal delivery. We concluded that the most predictive anthropometric measurement for vaginal delivery is maternal height. PMID- 21973134 TI - A postmenopausal woman developed a giant endometrial polyp during Raloxifene treatment. PMID- 21973135 TI - Challenges of immediate newborn care in maternity units in Lagos, Nigeria: an observational study. AB - Substandard newborn care has been identified as a major contributor to the estimated annual 4 million neonatal deaths and 1 million fresh stillbirths. Low income countries, including Nigeria account for more than 95% of all cases. A cross-sectional comparative study utilising non-participant observation methods was used to study perinatal care at two maternity centres in Lagos, Nigeria. Data on 63 mother-baby pairs were included in the study. Two stillbirths and two early neonatal deaths occurred during the study period, equally divided between the two hospitals. The partograph, a crucial tool for monitoring progress of labour, was in use in 77.4% vs 50% of cases at the two centres. The only interventions utilised for the prevention of hypothermia were drying and covering newborns with towels. Hygiene routines were poor and caring procedures did not demonstrate adequate knowledge related to a newborn's health. An enabling environment and supportive supervision is urgently required. PMID- 21973136 TI - Ovarian lymphoma. AB - Ovarian lymphomas are rare. We reviewed three cases seen at our hospital to determine any similarities and outcome. The women presented with abdominal discomfort and swelling and were staged as stage I, II and IV. All three cases were B-cell lymphomas confirmed with positive staining with CD45 (LCA), CD20 (L26), CD 45 (4KB) CD45RA (MB1) and MB2 on immunohistochemistry. The two patients with more advanced disease died soon after treatment but the one with stage I (primary ovarian lymphoma) was still alive after 2 years. Ovarian lymphoma when detected late carries a poor prognosis. PMID- 21973137 TI - Does post-caesarean dyspareunia reflect sexual malfunction, pelvic floor and perineal dysfunction? AB - The aim was to define post-caesarean dyspareunia as a sexual and pelvic-perineal symptom. Post-caesarean (80 elective, 104 emergency) and 100 vaginally delivered primiparae had domiciliary interviews at 10 months postpartum. A total of 50 (28% and 27%) post-caesarean and 46 (46%) vaginally delivered, reported dyspareunia. Severely impaired general sexual health occurred in 82 (24% elective, 25% emergency, 35% vaginally delivered) as category 3 (dyspareunia with sexual symptoms) and 27 (10% elective, 7% emergency, 12% vaginally delivered) as category 4 (reduced frequency < 6). The risk of dyspareunia (RR 1.14, CI 0.73, 1.77) or impaired general sexual health (RR 0.93, CI 0.32, 2.74) was similar among those with or without perineal trauma. Both caesarean and perineal scars were associated with sexual malfunction. Primiparae with new incontinence had a lower risk of dyspareunia than impaired general sexual health. Awareness of the associations of post-caesarean dyspareunia and impaired general sexual health with incontinence would facilitate appropriate obstetric decision-making. Further research is indicated. PMID- 21973138 TI - Adhesion reduction agents in gynaecological procedures: can NHS aff ord it? An economic cost efficiency analysis. AB - We examined the total costs to the National Health Service (NHS, UK) paid to treat adhesion complications and determine the theoretical savings and cost effectiveness incurred if anti-adhesion agents were adopted. Using Healthcare Resource Groups (HRG) codes, we calculated the costs incurred through Payment by Results (PbR) and then calculated the financial savings that could be realised through the use of anti-adhesion agents. There were 62,186 adhesion-related consultant episodes between 2004 and 2008 encountered within the NHS. If an anti adhesion agent cost L110 per usage, and can reduce adhesions in 25% of patients undergoing surgery, assuming that 25% of patients were readmitted in the first year after the primary surgery, the financial cost to the health service is, at best, savings of more than L700,000 and at worst, cost neutral to the NHS. PMID- 21973139 TI - Removal of intra-abdominal mislocated intrauterine devices by laparoscopy. AB - This retrospective study was carried out on 15 patients who underwent laparoscopy for the removal of a mislocated IUD from 2003 to 2009. The mean duration of usage of an IUD was 16.1 months. The IUD was found in the Pouch of Douglas in six patients; in the posterior wall of the uterus in three patients; in the adnexa in three patients; in the omentum in two patients and it was embedded in the rectal serosa in one patient. The types of the IUDs were TCu-380A (n = 13) and Mirena((r)) (n = 2). The mean laparoscopic operation time was 25 min. No major complications occurred. A second ancillary port was required in three patients. All patients were discharged within 24 h. Laparoscopic removal of the intra abdominal IUD must be the first choice of therapy. If possible, a single ancillary port should be preferred for the removal of mislocated IUDs. We advise that surgical removal and surgical risk should be discussed with the patients, even if asymptomatic. PMID- 21973140 TI - The relationship of sperm DNA fragmentation index with the outcomes of in-vitro fertilisation-embryo transfer and intracytoplasmic sperm injection. AB - This study was conducted to investigate the relationship between sperm DNA fragmentation index (DFI) and the outcomes of in-vitro fertilisation-embryo transfer (IVF-ET) and intracytoplasmic sperm injection (ICSI). Sperm DFI in 116 patients for IVF and 63 patients for ICSI were detected with acridine orange test (AOT), and all the cases were divided into DFI <= 30% group and DFI > 30% group according to the DFI value; then, the relationship of DFI with the outcomes of IVF/ICSI were analysed. Both in IVF and ICSI cycles, good embryo rate and spontaneous abortion rate in DFI > 30% group were significantly different from that in DFI <= 30% group, meanwhile, the fertilisation rate and cleavage rate were similar in two groups. In ICSI cycles, there was a significantly negative correlation between the DFI value and the rates of embryo implantation and pregnancy; the couples with DFI > 30% had significantly lower embryo implantation rate and pregnancy rate than the ones with DFI <= 30%. The receiver operating characteristics curve analysis demonstrated that the DFI value were statistically significant predictors of pregnancy. It is concluded that DNA-damaged sperm could have a potential adverse effect on embryo quality and progression of pregnancy as well as the outcomes of ICSI. PMID- 21973141 TI - Standards of care provided by early pregnancy assessment units (EPAU): a UK-wide survey. AB - Standards of services provided by the EPAUs across the UK vary from one unit to another. The aim of this purposive sampling self-administered survey was to assess these standards against a benchmark set by the Royal College of Obstetricians and Gynaecologists (RCOG). These standards were set out in a report by a RCOG working party (2008). Out of 181 units contacted in this survey, 140 units responded. We looked at the setup of the EPAU, services offered, accessibility and protocols for management of miscarriage and ectopic pregnancy. The survey shows that there is a considerable variation in the management protocols and the quality of services offered by the EPAUs in the UK. Many units do not meet the standards set by the RCOG. PMID- 21973142 TI - Surgical outcome of transobturator tape procedure in obese and non-obese women. AB - The objective of this study was to assess the impact of body mass index (BMI) on transobturator tape (TOT) success rates, patient acceptability and complications 1 year following surgery. The medical records of stress urinary incontinence (SUI) and mixed urinary incontinence (MUI) patients who underwent the TOT operation were retrospectively reviewed. The patients were divided into non-obese (BMI < 25) and obese (BMI >= 30) groups. Baseline and 1 year post-surgical outcomes were assessed by including multichannel urodynamics, Urogenital Distress Inventory (UDI-6) scores, Incontinence Impact Questionnaire (IIQ-7) scores and cure, failure and success rates. There were no significant differences between groups in terms of urodynamic parameters, objective cure rate and subjective success, quality of life scores, or postoperative complications. Both obese and non-obese patients had cure and/or improvement of their symptoms and had better quality-of-life in the postoperative period. As a conclusion, BMI does not affect the clinical effectiveness of TOT operation in the treatment of female SUI or MUI. PMID- 21973143 TI - High-risk human papilloma virus prevalence and its relation with abnormal cervical cytology among Turkish women. AB - In this study we aimed to investigate high-risk human papilloma virus (hrHPV) prevalence among Turkish women. Cervical samples were collected from 501 women for cytological screening and hrHPV testing by Digene Hybrid Capture 2. hrHPV prevalence and its relation with cytological results and epidemiologic data were analysed by SPSS. The prevalence of hrHPV was 4.2% (21 of the 501 women). Women with abnormal cytological screening results have significantly higher risk of hrHPV positivity compared with women with normal cytological results (19% vs 3.5%) (p <= 0.01). The incidence of HPV infection was only associated with the number of sexual partners, but there was no association with age, contraception methods or age at the first sexual intercourse. The prevalence of hrHPV among histological-confirmed cervical intraepithelial neoplasia (CIN) 1, CIN 2 and normal cases were found as 37.5%, 25% and 25%, respectively. The prevalence of cervical hrHPV infection is 4.2% in our population and this rate seems lower than reported rates from other regions. According to further studies with a larger sample size, reflex cytology based on hrHPV positivity should be considered for our national cervical cancer screening programme. PMID- 21973144 TI - Triploidy without molar change presenting as severe pre-eclampsia and left ventricular failure at 15 weeks. PMID- 21973145 TI - Pseudoaneurysm with arteriovenous fistula due to placenta increta following 1st trimester abortion. PMID- 21973146 TI - A case of pituitary apoplexy masquerading as hyperemesis gravidarum. PMID- 21973147 TI - Placental chorioangioma - an unusual cause of acute polyhydramnios with an isolated rise in maternal serum ALT: a clinical marker of disease and/or risk? PMID- 21973148 TI - Uneventful delivery with caesarean section in a woman with a history of endovascular management of an intracranial aneurysm. PMID- 21973149 TI - Prior caesarean section involving the uterine body, cerclage, pre-term labour contraction and uterine rupture. PMID- 21973150 TI - Five recurrent ectopic pregnancies in a patient with MUC1 expression deficiency. PMID- 21973151 TI - Use of mifepristone along with methotrexate in medical management of unruptured ectopic pregnancy. PMID- 21973152 TI - Favourable pregnancy outcome after endometrectomy for a Robert's uterus. PMID- 21973153 TI - Use of haemostatic glue for fistula prevention after iatrogenic combined rupture of anterior vaginal wall, bladder and urethra, during vaginal delivery. PMID- 21973154 TI - Prolapse of a large necrotic cervical fibroid. PMID- 21973155 TI - Spontaneous perforation of pyometra due to acute necrotising endometritis. PMID- 21973156 TI - A rare case of vulval leiomyosarcoma: management and an updated review of the literature. PMID- 21973160 TI - For she that hath, to her shall be given...Implications of flowering in Anemone nemorosa L. AB - We looked for life-history trade-offs between flowering, vegetative growth and somatic maintenance in the common woodland herb Anemone nemorosa. A. nemorosa forms a horizontal rhizome system consisting of previously formed annual segments and terminated by a flowering or non-flowering shoot. Resources acquired by the aboveground parts are used for flowering, seed production, storage and growth of the annual segments. Resources stored in the rhizome during the growing period are used for preformation of buds, somatic maintenance between two growing periods and development of aboveground parts in the following spring. We hypothesised that the decision to invest in flower buds depends on the amount of resources stored in the recently formed annual segment. We also hypothesised a trade-off between flowering and segment growth and, finally, as a consequence, we expected individual rhizomes to alternate between the flowering and the non flowering state. We found that segments producing flower buds were significantly longer than non-flowering segments, indicating that resource level influences the function of the preformed buds. Contrary to our expectations, we found flowering rhizomes produced longer annual segments than non-flowering rhizomes. We suggest the larger leaf area of flowering rhizomes and occasional abortion of flowers or seeds as possible mechanisms behind this pattern. Our study shows that even though the decision to produce a flower bud is taken in another time-frame than that in which the actual flowering and fruiting takes place, an ostensibly inexpedient decision is changed to a neutral or even an advantageous incident. PMID- 21973161 TI - Selecting predictors for discriminant analysis of species performance: an example from an amphibious softwater plant. AB - Selecting an appropriate variable subset in linear multivariate methods is an important methodological issue for ecologists. Interest often exists in obtaining general predictive capacity or in finding causal inferences from predictor variables. Because of a lack of solid knowledge on a studied phenomenon, scientists explore predictor variables in order to find the most meaningful (i.e. discriminating) ones. As an example, we modelled the response of the amphibious softwater plant Eleocharis multicaulis using canonical discriminant function analysis. We asked how variables can be selected through comparison of several methods: univariate Pearson chi-square screening, principal components analysis (PCA) and step-wise analysis, as well as combinations of some methods. We expected PCA to perform best. The selected methods were evaluated through fit and stability of the resulting discriminant functions and through correlations between these functions and the predictor variables. The chi-square subset, at P < 0.05, followed by a step-wise sub-selection, gave the best results. In contrast to expectations, PCA performed poorly, as so did step-wise analysis. The different chi-square subset methods all yielded ecologically meaningful variables, while probable noise variables were also selected by PCA and step-wise analysis. We advise against the simple use of PCA or step-wise discriminant analysis to obtain an ecologically meaningful variable subset; the former because it does not take into account the response variable, the latter because noise variables are likely to be selected. We suggest that univariate screening techniques are a worthwhile alternative for variable selection in ecology. PMID- 21973162 TI - Microbiology of the skin and the role of biofilms in infection. AB - The integrity of human skin is central to the prevention of infection. Acute and chronic wounds can develop when the integrity of skin as a barrier to infection is disrupted. As a multi-functional organ, skin possesses important biochemical and physical properties that influence its microbiology. These properties include a slightly acidic pH, a low moisture content, a high lipid content (which results in increased hydrophobicity) and the presence of antimicrobial peptides. Such factors have a role to play in preventing exogenous microbial colonisation and subsequent infection. In addition, the properties of skin both select for and enhance colonisation and biofilm formation by certain 'beneficial' micro organisms. These beneficial micro-organisms can provide further protection against colonisation by potential pathogens, a process known as colonisation resistance. The aim of this paper is to summarise the microflora of skin and wounds, highlighting the role of certain micro-organisms and biofilms in associated infections. PMID- 21973163 TI - Duodenal expression of iron transport molecules in patients with hereditary hemochromatosis or iron deficiency. AB - Disturbances of iron metabolism are observed in chronic liver diseases. In the present study, we examined gene expression of duodenal iron transport molecules and hepcidin in patients with hereditary hemochromatosis (HHC) (treated and untreated), involving various genotypes (genotypes which represent risk for HHC were examined), and in patients with iron deficiency anaemia (IDA). Gene expressions of DMT1, ferroportin, Dcytb, hephaestin, HFE and TFR1 were measured in duodenal biopsies using real-time PCR and Western blot. Serum hepcidin levels were measured using ELISA. DMT1, ferroportin and TFR1 mRNA levels were significantly increased in post-phlebotomized hemochromatics relative to controls. mRNAs of all tested molecules were significantly increased in patients with IDA compared to controls. The protein expression of ferroportin was increased in both groups of patients but not significantly. Spearman rank correlations showed that DMT1 versus ferroportin, Dcytb versus hephaestin and DMT1 versus TFR1 mRNAs were positively correlated regardless of the underlying cause, similarly to protein levels of ferroportin versus Dcytb and ferroportin versus hephaestin. Serum ferritin was negatively correlated with DMT1 mRNA in investigated groups of patients, except for HHC group. A decrease of serum hepcidin was observed in IDA patients, but this was not statistically significant. Our data showed that although untreated HHC patients do not have increased mRNA levels of iron transport molecules when compared to normal subjects, the expression is relatively increased in relation to body iron stores. On the other hand, post-phlebotomized HHC patients had increased DMT1 and ferroportin mRNA levels possibly due to stimulated erythropoiesis after phlebotomy. PMID- 21973164 TI - Methicillin-susceptible Staphylococcus aureus clone related to the early pandemic phage type 80/81 causing an outbreak among residents of three occupational centres in Barcelona, Spain. AB - In the 1950s an unusually virulent and transmissible penicillin-resistant Staphylococcus aureus clone harbouring Panton-Valentine leukocidin (PVL) genes, known as phage type 80/81 and subsequently identified as multilocus sequence type (ST) 30, emerged and caused serious infections in hospitals and the community. We describe an outbreak of skin infections caused by a PVL-positive, methicillin susceptible S. aureus (MSSA) strain of ST1472, related to phage type 80/81, in three associated occupational centres. After identification of the first patient an active case-finding strategy was initiated among the three centres. Epidemiological and clinical features were indistinguishable from outbreaks currently caused by community-acquired methicillin-resistant S. aureus. The S. aureus was cultured and identified from nasal swabs and skin lesions by conventional methods; PVL was detected using a PCR assay. Pulsed-field gel electrophoresis and DNA-array-based genotyping were applied to MSSA isolates. MSSA was identified in nasal swabs from 49 of 133 individuals (37%). A single pulsed-field gel electrophoresis pattern, belonging to ST1472 (CC30) and PVL positivity, were detected in 20 individuals, including eight of 18 skin cultures, i.e. 15% of the screened individuals were colonized by the epidemic strain. Nasal and cutaneous decontamination with 5% nasal mupirocin ointment and 2% aqueous chlorhexidine was implemented for all individuals. Patients with active skin infections were treated with a first-generation cephalosporin. General recommendations were made to prevent cross-transmission. No new cases were reported over the following 90 days. PMID- 21973165 TI - (-)-Epigallocatechin gallate suppresses proliferation of vascular smooth muscle cells induced by high glucose by inhibition of PKC and ERK1/2 signalings. AB - Proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the development and progression of diabetes-related vascular complications. (-) Epigallocatechin gallate (EGCG), the major catechin derived from green tea, is able to exert antidiabetes effects in animal models. However, it is not known whether or not EGCG inhibits VSMC proliferation induced by high glucose. This study tested the hypothesis that EGCG might have an inhibitory effect on VSMC proliferation induced by high glucose. VSMC proliferation was determined by [(3)H]-thymidine incorporation and uptake of 3-(4,5-dimethylthiazol-2-yl) diphenyltetrazolium bromide (MTT). Extracellular signal-regulated kinase (ERK) 1/2 phosphorylation was determined by immunoblotting, and ERK 1/2 activity was detected by measuring the ability to phosphorylate its substrate Elk-1. Glucose increased VSMC proliferation in a concentration-dependent manner, which was reduced in the presence of EGCG. VSMC proliferation mediated by high glucose (30 mM) was involved in protein kinase C (PKC) and ERK1/2 signalings, because its effect was blocked by PKC inhibitor (PKC inhibitor 19-31) and ERK1/2 inhibitor (PD98059). Pretreatment of VSMCs with EGCG significantly inhibited the stimulatory effect of high glucose on PKC and ERK1/2 activation, followed by attenuation of its downstream transcription factor Elk-1 phosphorylation. Taken together, these results suggest that EGCG could suppress VSMC proliferation induced by high glucose by inhibition of PKC and ERK1/2 signalings in VSMCs, which indicates that EGCG might be a possible medicine to reduce vascular complications in diabetes. PMID- 21973166 TI - Prismaflex HF20 for continuous renal replacement therapy in critically ill children. PMID- 21973167 TI - Cell surface markers CD44 and CD166 localized specific populations of salivary acinar cells. AB - OBJECTIVE: Experimental approaches tested to date for functional restoration of salivary glands (SGs) are tissue engineering, gene transfer, and cell therapy. To further develop these therapies, identifying specific cell surface markers for the isolation of salivary acinar cells is needed. To test a panel of cell surface markers [used in the isolation of mesenchymal stem cells, (MSCs)] for the localization of salivary acinar cells. MATERIALS: Human submandibular and parotid glands were immunostained with a panel of MSC markers and co-localized with salivary acinar cell differentiation markers [alpha-amylase, Na-K-2Cl cotransporter-1, aquaporin-5 (AQP5)]. Additional cell markers were also used, such as alpha-smooth muscle actin (to identify myoepithelial cells), cytokeratin 5 (basal ductal cells), and c-Kit (progenitor cells). RESULTS: CD44 identified serous acini, while CD166 identified mucous acini. Cytokeratin-5 identified basal duct cells and 50% of myoepithelial cells. None of the remaining cell surface markers (Stro-1, CD90, CD106, CD105, CD146, CD19, CD45, and c-Kit) were expressed in any human salivary cell. CONCLUSIONS: CD44 and CD166 localized human salivary serous and mucous acinar cells, respectively. These two cell surface markers will be useful in the isolation of specific populations of salivary acinar cells. PMID- 21973169 TI - Correlation between point-of-care platelet function testing and bleeding after coronary artery surgery. AB - OBJECTIVES: To investigate whether point-of-care platelet function testing immediately before coronary artery bypass grafting correlates to postoperative blood loss and transfusion requirements. DESIGN: Blood samples from 50 patients on antiplatelet therapy were analysed by Plateletworks((r)). Thirty-three of the patients had received clopidogrel, 300-600 mg loading dose followed by 75 mg once daily, within 7 days. Postoperative chest drainage volume was recorded every hour. RESULTS: Plateletworks((r)) ADP-induced platelet aggregation correlated significantly to postoperative chest drainage volume at 5 hours (r = -0.83; p < 0.01) and 12 hours (r = -0.55; p < 0.01), and the tertile of patients with the lowest aggregation had higher postoperative transfusion requirements (p < 0.01) and about three times larger chest drainage volume than remaining patients during the first 5 hours after surgery (p < 0.01). Cessation of clopidogrel correlated to chest drainage volume at 5 hours (r = -0.48; p < 0.01) and 12 hours (r = 0.47; p < 0.01) after surgery. CONCLUSIONS: The significant correlation between Plateletworks((r)) ADP-induced platelet aggregation and blood loss suggests that this test may be useful to predict risk of excessive bleeding and to guide timing of surgery and bleeding treatment in patients undergoing coronary artery bypass grafting. PMID- 21973168 TI - YY1 negatively regulates mouse myelin proteolipid protein (Plp1) gene expression in oligodendroglial cells. AB - YY1 (Yin and Yang 1) is a multifunctional, ubiquitously expressed, zinc finger protein that can act as a transcriptional activator, repressor, or initiator element binding protein. Previous studies have shown that YY1 modulates the activity of reporter genes driven by the myelin PLP (proteolipid protein) (PLP1/Plp1) promoter. However, it is known that Plp1 intron 1 DNA contains regulatory elements that are required for the dramatic increase in gene activity, coincident with the active myelination period of CNS (central nervous system) development. The intron in mouse contains multiple prospective YY1 target sites including one within a positive regulatory module called the ASE (anti silencer/enhancer) element. Results presented here demonstrate that YY1 has a negative effect on the activity of a Plp1-lacZ fusion gene [PLP(+)Z] in an immature oligodendroglial cell line (Oli-neu) that is mediated through sequences present in Plp1 intron 1 DNA. Yet YY1 does not bind to its alleged site in the ASE (even though the protein is capable of recognizing a target site in the promoter), indicating that the down-regulation of PLP(+)Z activity by YY1 in Oli neu cells does not occur through a direct interaction of YY1 with the ASE sequence. Previous studies with Yy1 conditional knockout mice have demonstrated that YY1 is essential for the differentiation of oligodendrocyte progenitors. Nevertheless, the current study suggests that YY1 functions as a repressor (not an activator) of Plp1 gene expression in immature oligodendrocytes. Perhaps YY1 functions to keep the levels of PLP in check in immature cells before vast quantities of the protein are needed in mature myelinating oligodendrocytes. PMID- 21973170 TI - Intra-arterial blood pressure reading in intensive care unit patients in the lateral position. AB - BACKGROUND: Routine lateral turning of patients has become an accepted standard of care to prevent complications of immobility. The haemodynamic and oxygenation effects for patients in both lateral positions (45 degrees ) are still a matter of debate. We aimed to study the effect of these positions on blood pressure, heart rate and oxygenation in a general intensive care population. DESIGN: Observational study. METHOD: Twenty stable intensive care unit patients had intra arterial blood pressure recordings in the supine and lateral positions with the correction of hydrostatic height compared with a fixed reference point (phlebostatic level). A multilevel model was used to analyse the data. RESULTS: Mean arterial pressure readings in the lateral positions were, on average, 5 mmHg higher than in the supine position (p < 0.001). There were no significant differences between mean arterial pressure recordings in the left and right lateral position (p = 1.0). No important differences in oxygenation and heart rate were observed. After correction for covariates, the effects persisted. CONCLUSION: Our study demonstrated an increase, albeit small, in blood pressure in the lateral positions. No major differences between the left and right lateral position were found. No important differences in oxygenation and heart rate were observed. RELEVANCE TO CLINICAL PRACTICE: Turning haemodynamically stable patients in the intensive care unit has no important effects on blood pressure measurements when continuous hydrostatic height correction is applied. PMID- 21973171 TI - Analysis of the subcellular localisation of lipoxygenase in legume and actinorhizal nodules. AB - Plant lipoxygenases (LOXs; EC 1.13.11.12) catalyse the oxygenation of polyunsaturated fatty acids, linoleic (18:2) and alpha-linolenic acid (18:3(n-3)) and are involved in processes such as stress responses and development. Depending on the regio-specificity of a LOX, the incorporation of molecular oxygen leads to formation of 9- or 13-fatty acid hydroperoxides, which are used by LOX itself as well as by members of at least six different enzyme families to form a series of biologically active molecules, collectively called oxylipins. The best characterised oxylipins are the jasmonates: jasmonic acid (JA) and its isoleucine conjugate that are signalling compounds in vegetative and propagative plant development. In several types of nitrogen-fixing root nodules, LOX expression and/or activity is induced during nodule development. Allene oxide cyclase (AOC), a committed enzyme of the JA biosynthetic pathway, has been shown to localise to plastids of nodules of one legume and two actinorhizal plants, Medicago truncatula, Datisca glomerata and Casuarina glauca, respectively. Using an antibody that recognises several types of LOX interspecifically, LOX protein levels were compared in roots and nodules of these plants, showing no significant differences and no obvious nodule-specific isoforms. A comparison of the cell specific localisation of LOXs and AOC led to the conclusion that (i) only cytosolic LOXs were detected although it is generally assumed that the (13S) hydroperoxy alpha-linolenic acid for JA biosynthesis is produced in the plastids, and (ii) in cells of the nodule vascular tissue that contain AOC, no LOX protein could be detected. PMID- 21973172 TI - Identification of a panel of novel serum osteoarthritis biomarkers. AB - Osteoarthritis (OA) is the most common rheumatic pathology. Because currently available diagnostic methods are limited and lack sensitivity, the identification of new specific biological markers for OA has become a focus. The purpose of this study was to identify novel protein biomarkers for moderate and severe OA in serum. Sera were obtained from 50 moderate OA patients, 50 severe OA patients, and 50 nonsymptomatic controls. Serum protein levels were analyzed using isobaric tags for relative and absolute quantitation (iTRAQ) and matrix-assisted laser desorption/ionization (MALDI)-TOF/TOF mass spectrometry. We identified 349 different proteins in the sera, 262 of which could be quantified by calculation of their iTRAQ ratios. Three sets of proteins were significantly (p < 0.05) changed in OA samples compared to controls. Of these, 6 were modulated only in moderate OA, 13 only in severe OA and 7 in both degrees. Although some of these proteins, such as cartilage oligomeric matrix protein, have a previously reported putative biomarker value for OA, most are novel biomarker candidates for the disease. These include some complement components, lipoproteins, von Willebrand factor, tetranectin, and lumican. The specificity and selectivity of these candidates need to be validated before new molecular diagnostic or prognostic tests for OA can be developed. PMID- 21973173 TI - Mass balance of total mercury and monomethylmercury in coastal embayments of a volcanic island: significance of submarine groundwater discharge. AB - To understand the contribution of submarine groundwater discharge (SGD) to the coastal mass budgets of Hg and monomethylmercury (MMHg), preliminary mass balance estimates were made for Hwasun and Bangdu Bays on Jeju Island, known to have large SGD due to the high permeability of the volcanic rocks. The mass balance results indicate that SGD is a main source of Hg in Hwasun Bay (23 +/- 14 * 10( 2) mol yr(-1), 34%) and Bangdu Bay (23 +/- 20 * 10(-2) mol yr(-1), 67%), although the contribution from atmospheric deposition was considerable (25% for Hwasun and 23% for Bangdu). MMHg was also discharged primarily from submarine groundwater at Hwasun (0.30 +/- 0.17 * 10(-2) mol yr(-1), 55%) and Bangdu (0.65 +/- 0.49 * 10( 2) mol yr(-1), 64%), which was higher than atmospheric deposition (6% for Hwasun and 2% for Bangdu) and sediment diffusion flux (5% for Hwasun and 3% for Bangdu). The overall mass balance results suggest that, although there are large spatial variations in SGD rates throughout the region, the coastal mass budgets of Hg and MMHg need to include SGD as well as atmospheric deposition and sediment diffusion as primary sources of Hg and MMHg. PMID- 21973174 TI - Effect of cross-fostering on renal anti-oxidant/oxidant status and development of hypertension in spontaneously hypertensive rats. AB - 1. The hypotensive effect of cross-fostering in spontaneously hypertensive rats (SHR) is thought to involve adjustments in renal function. However, its association with renal anti-oxidant/oxidant balance during cross-fostering is not known. 2. The present study examined the effect of cross-fostering and in fostering of 1-day-old offspring between SHR and Wistar-Kyoto (WKY) dams on renal anti-oxidant/oxidant status and systolic blood pressure (SBP). Renal anti oxidant/oxidant status and SBP were determined in the offspring from 4-16 weeks of age. 3. Cross-fostered SHR had significantly lower SBP than in-fostered SHR at 6, 8 and 12 weeks, but not at 16 weeks (127 +/- 1 vs 144 +/- 2, 138 +/- 1 vs 160 +/- 1, 174 +/- 2 vs 184 +/- 2 and 199 +/- 2 vs 194 +/- 3 mmHg at 6, 8, 12 and 16 weeks, respectively). No differences in SBP were evident between cross-fostered and in-fostered WKY rats. There were no significant differences in levels of thiobarbituric acid-reactive substances (TBARS), protein carbonyl and total anti oxidant status (TAS) or superoxide dismutase, catalase, glutathione peroxidase (GPx), glutathione S-transferase and glutathione reductase activity between cross fostered and in-fostered SHR or WKY offspring. However, compared with WKY rats, catalase activity was higher at 6 and 16 weeks, TAS was higher at 16 weeks and GPx activity and TBARS were lower at 16 weeks in SHR. 4. It appears that cross fostering of SHR offspring to WKY dams during the early postnatal period causes a transient delay in the rise in blood pressure in SHR and that this does not involve the renal anti-oxidant/oxidant system. PMID- 21973175 TI - Retrospective study of 24 patients with large or small plaque parapsoriasis treated with ultraviolet B therapy. PMID- 21973176 TI - Copper(I) catalyzed regioselective asymmetric alkoxyamination of aryl enamide derivatives. AB - The copper(I) catalyzed reaction of an enamide with an iminoiodane, in the presence of an alcohol, triggers the direct alkoxyamination of the double bond. This transformation represents a straightforward access to alpha-amino aminals in a completely regio- and diastereoselective manner. Use of a chiral Box ligand allows this reaction to be carried out in an enantioselective fashion. PMID- 21973177 TI - Accelerated healing of diabetic wounds by NorLeu(3)-angiotensin (1-7). AB - INTRODUCTION: Diabetes is a disorder that is well known to delay wound repair resulting in the formation of colonized, chronic wounds. The resultant ulcers contribute to increased risk of morbidity, including osteomyelitis and amputations, and increased burden to the healthcare system. AREAS COVERED: The only active product approved for the treatment of diabetic ulcers, Regranex, has been shown to reduce amputation risk, but is not widely used due to minimal proven efficacy and recent warnings added to the Instructions for Use. This review provides an overview of the development of NorLeu(3)-angiotensin (1-7) (NorLeu(3)-A(1-7)) as an active agent for the treatment of diabetic wounds. NorLeu(3)-A(1-7) is an analog of the naturally occurring peptide, angiotensin 1 7. The mechanisms of action include induction of progenitor proliferation and accelerated vascularization, collagen deposition and re-epithelialization. EXPERT OPINION: Research to date has shown that NorLeu(3)-A(1-7) is highly effective in the closure of diabetic wounds and is superior to Regranex in animal studies. Further clinical development of this product as a topical agent for the healing of chronic wounds and investigation into the mechanisms by which this product accelerates healing are warranted. PMID- 21973178 TI - Conostegia xalapensis (Melastomataceae): an aluminum accumulator plant. AB - In acidic soils, an excess of Al3+ is toxic to most plants. The Melastomataceae family includes Al-accumulator genera that tolerate high Al3+ by accumulating it in their tissues. Conostegia xalapensis is a common shrub in Mexico and Central America colonizing mainly disturbed areas. Here, we determined whether C. xalapensis is an Al accumulator, and whether it has internal tolerance mechanisms to Al. Soil samples collected from two pastures in the state of Veracruz, Mexico, had low pH and high Al3+ concentrations along with low Ca2+ levels. Leaves of C. xalapensis from pastures showed up to 19,000 mg Al kg-1 DW (dry weight). In laboratory experiments, 8-month-old seedlings treated with 0.5 and 1.0 mM AlCl3 for 24 days showed higher number of lateral roots and biomass. Pyrocatechol violet and hematoxylin staining evidenced that Al localized in epidermis and mesophyll cells in leaves and in epidermis and vascular pith in roots. Scanning electron microscope-energy dispersive X-ray microanalysis of Al-treated leaves corroborated that Al is in abaxial and adaxial epidermis and in mesophyll cells (31.2%) in 1.0 mM Al-treatment. Roots of Al-treated plants had glutathione reductase (EC 1.6.4.2) and superoxide dismutase (EC 1.15.1.1) activity higher, and low levels of O2*- and H2O2. C. xalapensis is an Al-accumulator plant that can grow in acidic soils with higher Al3+ concentrations, and can be considered as an indicator species for soils with potential Al toxicity. PMID- 21973179 TI - The causes and consequences of demographic transition. PMID- 21973180 TI - Diastereocontrol in asymmetric allyl-allyl cross-coupling: stereocontrolled reaction of prochiral allylboronates with prochiral allyl chlorides. AB - Palladium-catalyzed allyl-allyl cross-coupling was investigated with substituted prochiral allylic boronates. These reactions deliver products bearing adjacent stereocenters, and the issue of diastereocontrol is therefore paramount. Under appropriately modified conditions, this allyl-allyl coupling strategy was found to apply to a range of substrates, generally occurring with high enantioselectivity (92:8 to >99:1 er) and good diastereoselection (4:1 to 14:1 dr). PMID- 21973181 TI - Response to first antiepileptic drug trial predicts health outcome in epilepsy. AB - PURPOSE: Failure to respond to the initial antiepileptic drug (AED) is a predictor of increased risk of pharmacoresistant epilepsy. Whether response to the first AED also predicts adverse health outcomes is unknown. METHODS: This longitudinal study compared rates of major adverse health outcomes (loss of driving privileges, unemployment, divorce/separation, injury, emergency room admission, hospitalization, and death) in 33 patients who failed the first AED (cases) and 30 patients who became seizure-free with the first AED (controls). Patient data were obtained by chart review and confirmed through a structured interview with each subject at 5-7 years after starting AED treatment. We also assessed between-group differences in quality of life, depression, and adverse AED effects by using standardized instruments completed by each subject at the end of follow-up. KEY FINDINGS: The number of major adverse health outcomes was similarly high during the first year of AED treatment [mean +/- standard deviation (SD) 2.64 +/- 0.99 for cases and 2.50 +/- 1.14 for controls], but thereafter decreased to a greater extent in controls than in cases (p < 0.001). Controls had a higher cumulative probability of experiencing >=1 year free from major adverse health outcomes compared to cases (p = 0.002). Two cases died during the follow-up, both of sudden unexpected death. Cases had worse quality of life ratings than controls, whereas no significant between-group differences were found for measures of depression and adverse AED effects. In a post hoc analysis limited to cases, patients who became seizure-free with subsequent AED treatments showed for the first 4 years major adverse health outcome rates similar to those recorded in patients with persisting seizures. After 4 years, however, cases who achieved late seizure freedom tended to show a more favorable outcome. SIGNIFICANCE: Patients with epilepsy failing the initial AED trial are at increased risk of experiencing adverse health outcomes, at least for the first 4 years after diagnosis. Incorporating these findings into clinical decision making may aid in reducing delays in surgical referrals for pharmacoresistant epilepsy. PMID- 21973182 TI - Salicylic acid negatively affects the response to salt stress in pea plants. AB - We studied the effect of salicylic acid (SA) treatment on the response of pea plants to salinity. Sodium chloride (NaCl)-induced damage to leaves was increased by SA, which was correlated with a reduction in plant growth. The content of reduced ascorbate and glutathione in leaves of salt-treated plants increased in response to SA, although accumulation of the respective oxidised forms occurred. An increase in hydrogen peroxide also occurred in leaves of salt-exposed plants treated with SA. In the absence of NaCl, SA increased ascorbate peroxidase (APX; 100 MUm) and glutathione-S transferase (GST; 50 MUm) activities and increased catalase (CAT) activity in a concentration-dependent manner. Salinity decreased glutathione reductase (GR) activity, but increased GST and CAT activity. In salt stressed plants, SA also produced changes in antioxidative enzymes: 100 MUm SA decreased APX but increased GST. Finally, a concentration-dependent increase in superoxide dismutase (SOD) activity was induced by SA treatment in salt-stressed plants. Induction of PR-1b was observed in NaCl-stressed plants treated with SA. The treatment with SA, as well as the interaction between salinity and SA treatment, had a significant effect on PsMAPK3 expression. The expression of PsMAPK3 was not altered by 70 mm NaCl, but was statistically higher in the absence than in the presence of SA. Overall, the results show that SA treatment negatively affected the response of pea plants to NaCl, and this response correlated with an imbalance in antioxidant metabolism. The data also show that SA treatment could enhance the resistance of salt-stressed plants to possible opportunistic pathogen attack, as suggested by increased PR-1b gene expression. PMID- 21973183 TI - Correlation of cytological and biochemical parameters with resistance and tolerance to Mycosphaerella graminicola in wheat. AB - This study investigated the infection process of Mycosphaerella graminicola and enzyme activities related to reactive oxygen species (ROS) or oxylipin biosynthesis in four French wheat cultivars with variable resistance to M. graminicola infection. At field level, cultivars Caphorn, Maxyl and Gen11 were susceptible, whereas Capnor showed high levels of quantitative resistance. Moreover, Capnor and Gen11 were tolerant, i.e., their yield was less affected by infection compared to non-tolerant Maxyl and Caphorn. These four cultivars were inoculated under laboratory conditions with the M. graminicola IPO323 reference strain. Cytological and biochemical responses were studied on collected first plantlet leaves and several features discriminated between cultivars. However, resistance and tolerance had no impact on the fungal infection process. Levels of lipoxygenase (LOX), peroxidase (PO) and glutathione-S-transferase (GST) activities were also compared with regard to cultivar resistance or tolerance to M. graminicola. LOX, PO and GST activities did not discriminate resistance and tolerance profiles, although a low level of PO in inoculated and non-inoculated plants could be associated with tolerance. In addition, cell necrosis correlated positively with LOX in non-tolerant cultivars, while mycelia surrounding stomata were positively correlated with PO in the resistant cultivar. GST activity presented correlations between cytological and biochemical parameters only for susceptible cultivars. Stomatal and direct penetration were positively correlated with GST activity in the susceptible non-tolerant cultivars, while these correlations were negative in the tolerant cultivar. When combining cytological and biochemical observations with resistance and tolerance profiles, for each cultivar and at each time point, cultivars could be classified in tight accordance with their previous field characterisation. Moreover, tolerance allowed us to distinguish susceptible cultivars when both biochemical and cytological parameters were considered together. PMID- 21973184 TI - Effect of temperature on the progamic phase in high-mountain plants. AB - Progamic processes are particularly temperature-sensitive and, in lowland plants, are usually drastically reduced below 10 degrees C and above 30 degrees C. Little is known about how effectively sexual processes of mountain plants function under the large temperature fluctuations at higher altitudes. The present study examines duration and thermal thresholds for progamic processes in six common plant species (Cerastium uniflorum, Gentianella germanica, Ranunculus alpestris, R. glacialis, Saxifraga bryoides, S. caesia) from different altitudinal zones in the European Alps. Whole plants were collected from natural sites shortly before anthesis and kept in a climate chamber until further processing. Flowers with receptive stigmas were hand-pollinated with allopollen and exposed to controlled temperatures between -2 and 40 degrees C. Pollen performance (adhesion to the stigma, germination, tube growth, fertilisation) was quantitatively analysed, using the aniline blue fluorescence method. Pollen adhesion was possible from -2 to 40 degrees C. Pollen germination and tube growth occurred from around 0 to 35 degrees C in most species. Fertilisation was observed from 5 to 30-32 degrees C (0-35 degrees C in G. germanica). The progamic phase was shortest in G. germanica (2 h at 30 degrees C, 12 h at 5 degrees C, 24 h at 0 degrees C), followed by R. glacialis (first fertilisation after 2 h at 30 degrees C, 18 h at 5 degrees C). In the remaining species, first fertilisation usually occurred after 4-6 h at 30 degrees C and after 24-30 h at 5 degrees C. Thus, mountain plants show remarkably flexible pollen performance over a wide temperature range and a short progamic phase, which may be essential for successful reproduction in the stochastic high-mountain climate. PMID- 21973185 TI - European dissemination of a single OXA-48-producing Klebsiella pneumoniae clone. AB - A Klebsiella pneumoniae isolate with decreased susceptibility to carbapenems was isolated in April 2011 in a hospital in Amsterdam (the Netherlands) and later found to be the source of an important outbreak in a Rotterdam hospital. The strain, belonging to sequence type (ST) 395, carried the bla(OXA-48) gene located onto a c 62-kb conjugative plasmid, together with the extended-spectrum beta lactamase gene bla(CTX-M-15) . It was closely related or identical to other OXA 48-positive Klebsiella pneumoniae isolates belonging to the same ST type and identified in France and Morocco. This study sheds light on the European dissemination of a single OXA-48 K. pneumoniae clone. PMID- 21973186 TI - Structure characterization and antioxidant activity of a novel polysaccharide isolated from pulp tissues of Litchi chinensis. AB - A novel polysaccharide (LCP50S-2) with antioxidant activity was isolated from Litchi chinensis Sonn. The structure of LCP50S-2 was elucidated on the basis of physicochemical and instrumental analyses, and its average molecular weight was determined by gel permeation chromatography to be 2.19 * 10(2) kDa. The backbone of LCP50S-2 was composed of (1->3)-linked beta-L-rhamnopyranosyl residues, (1->4) linked alpha-D-xylopyranosyl residues, (1->4)-linked beta-D-glucopyranosyl residues, and (1->4)-linked alpha-D-glucopyranosyl residues which branched at O 6. The two branches consisted of alpha-L-arabinopyranosyl residues and (1->6) linked beta-D-galactopyranosyl residues terminated with alpha-L-arabinopyranosyl residues, respectively. In the in vitro antioxidant assay, LCP50S-2 was found to possess DPPH radical-scavenging activity and hydroxyl radical-scavenging activity with IC(50) values of 220 and 266 MUg/mL, respectively. PMID- 21973187 TI - A new tool for the molecular identification of Culicoides species of the Obsoletus group: the glass slide microarray approach. AB - Culicoides species of the Obsoletus group (Diptera: Ceratopogonidae) are potential vectors of bluetongue virus serotype 8 (BTV 8), which was introduced into central Western Europe in 2006. Correct morphological species identification of Obsoletus group females is especially difficult and molecular identification is the method of choice. In this study we present a new molecular tool based on probe hybridization using a DNA microarray format to identify Culicoides species of the Obsoletus group. The internal transcribed spacer 1 (ITS1) gene sequences of 55 Culicoides belonging to 13 different species were determined and used, together with 19 Culicoides ITS1 sequences sourced from GenBank, to design species-specific probes for the microarray test. This test was evaluated using the amplified ITS1 sequences of another 85 Culicoides specimens, belonging to 11 species. The microarray test successfully identified all samples (100%) of the Obsoletus group, identifying each specimen to species level within the group. This test has several advantages over existing polymerase chain reaction (PCR) based molecular tools, including possible capability for parallel analysis of many species, high sensitivity and specificity, and low background signal noise. Hand-spotting of the microarray slide and the use of detection chemistry make this alternative technique affordable and feasible for any diagnostic laboratory with PCR facilities. PMID- 21973188 TI - Composition analysis and material characterization of an emulsifying extracellular polysaccharide (EPS) produced by Bacillus megaterium RB-05: a hydrodynamic sediment-attached isolate of freshwater origin. AB - AIMS: This work was aimed to isolate, purify and characterize an extracellular polysaccharide (EPS) produced by a freshwater dynamic sediment-attached micro organism, Bacillus megaterium RB-05, and study its emulsifying potential in different hydrocarbon media. METHODS AND RESULTS: Bacillus megaterium RB-05 was found to produce EPSs in glucose mineral salts medium, and maximum yield (0.864 g l(-1) ) was achieved after 24-h incubation. The recovery rates of the polysaccharide material by ion-exchange and gel filtration chromatography were around 67 and 93%, respectively. As evident from HPLC and FT-IR analyses, the polysaccharide was found to be a heteropolymer-containing glucose, galactose, mannose, arabinose, fucose and N-acetyl glucosamine. Different oligosaccharide combinations namely hexose(3), hexose(4), hexose(5) deoxyhexose(1) and hexose(5) deoxyhexose(1) pentose(3) were obtained after partial hydrolysis of the polymer using MALDI-ToF-MS. The polysaccharide with an average molecular weight of 170 kDa and thermal stability up to 180 degrees C showed pseudoplastic rheology and significant emulsifying activity in hydrocarbon media. CONCLUSIONS: Isolated polysaccharide was found to be of high molecular weight and thermally stable. The purified EPS fraction was composed of hexose, pentose and deoxyhexose sugar residues, which is a rare combination for bacterial polysaccharides. Emulsifying property was either better or comparable to that of other commercially available natural gums and polysaccharides. SIGNIFICANCE AND IMPACT OF THE STUDY: This is probably one of the few reports about characterizing an emulsifying EPS produced by a freshwater sediment-attached bacterium. The results of this study contribute to understand the influence of chemical composition and material properties of a new microbial polysaccharide on its application in industrial biotechnology. Furthermore, this work reconfirms freshwater dynamic sediment as a potential habitat for bioprospecting extracellular polymer-producing bacteria. This study will improve our knowledge on the exploitation of a nonconventional renewable resource, which also seems to be ecologically significant. PMID- 21973189 TI - Translation of a minigene in the 5' leader sequence of the enterohaemorrhagic Escherichia coli LEE1 transcription unit affects expression of the neighbouring downstream gene. AB - The 5' end of the major RNA transcript of the LEE1 operon of enterohaemorrhagic Escherichia coli contains ~170 bases before the AUG translation start codon of the first recognized gene, ler. This unusually long leader sequence carries three potential alternative AUG start codons. Using a lac fusion expression vector, we confirmed that the ler gene AUG is functional for translation initiation, and we checked for translation initiation at the three alternative AUG codons. Whereas two of the alternative AUG codons appear incompetent for translation initiation, we detected strong initiation at the third AUG, which is followed by one AAA codon and a UAG stop codon. The location of this very short two-codon open reading frame with respect to the ler translation start appears to be critical. Hence mutations that destroy the UAG stop codon, or short deletions between the UAG stop codon and the ler translation initiation region, result in big effects on ler expression. In the context of the full-length LEE1 operon leader sequence, translation of this very short two-codon open reading frame is necessary for optimal expression of the ler gene and for the subsequent interactions of enterohaemorrhagic Escherichia coli with host target cells. PMID- 21973190 TI - Human umbilical cord mesenchymal stem cells suppress breast cancer tumourigenesis through direct cell-cell contact and internalization. AB - The purpose of this study was to investigate how human umbilical cord mesenchymal stem cells (HUMSCs) affect breast cancer tumourigenesis. To observe the influence of HUMSCs on tumourigenesis in vitro, we performed a co-culture of MDA MB-231 breast cancer cells with HUMSCs, and a result of HUMSCs on tumourigenesis in vivo was achieved by injection of HUMSCs into nonobese diabetic/severe combined immunodeficient mice following tumour establishment with MDA-MB231. During the co culture, apoptosis of MDA-MB231 was noted, which was driven either by binding with HUMSC through direct cell-cell contact or by formation of a novel cell-in cell phenomenon after internalization of HUMSC. Also, treatment with HUMSC injection was efficacious in both in situ and metastatic breast cancers in the animal models. Since HUMSCs were proved to efficaciously suppress breast cancer tumourigenesis both in vitro and in vivo, it is our expectation that treatment with HUMSCs can be a viable therapy for breast cancer in the near future. In addition, we share a new point of view on the role of HUMSCs in foetal development during pregnancy. PMID- 21973191 TI - Duodenal surveillance improves the prognosis after duodenal cancer in familial adenomatous polyposis. AB - AIM: Duodenal adenomatosis in familial adenomatous polyposis results in a cancer risk that increases with age. Endoscopic surveillance has been recommended, but the effect has not yet been documented. The aim of this study was to present the results of long-term duodenal surveillance and to evaluate the risk of cancer development. METHOD: Follow up of patients in a previous study with gastroduodenoscopy in 1990-2010. Statistical analysis included the chi(2) test, actuarial method and Kaplan-Meier analysis. RESULTS: Among 304 patients, 261 (86%) had more than one endoscopy. The median follow up was 14 (interquartile range, 9-17) years. The cumulative lifetime risk of duodenal adenomatosis was 88% (95% CI, 84-93), and of Spigelman stage IV was 35% (95% CI, 25-45). The Spigelman stage improved in 32 (12%) patients, remained unchanged in 88 (34%) and worsened in 116 (44%). Twenty (7%) patients had duodenal cancer at a median age of 56 (range, 44-82) years. The cumulative cancer incidence was 18% at 75 years of age (95% CI, 8-28) and increased with increasing Spigelman stage at the index endoscopy to 33% in Spigelman stage IV (P < 0.0001). The median overall survival was 6.4 years (95% CI, 1.7 to not estimated): 8 years after a screen-detected cancer vs 0.8 years (95% CI, 0.03-1.7) after a symptomatic cancer (P < 0.0001). The location of the mutation in the APC gene did not influence the risk of developing Spigelman stage IV (P = 0.46) or duodenal cancer (P = 0.83). CONCLUSION: The risk of duodenal cancer in familial adenomatous polyposis is considerable, and regular surveillance and cancer prophylactic surgery result in a significantly improved prognosis. PMID- 21973192 TI - Heterozygosity-fitness correlations in a migratory bird: an analysis of inbreeding and single-locus effects. AB - Studies in a multitude of taxa have described a correlation between heterozygosity and fitness and usually conclude that this is evidence for inbreeding depression. Here, we have used multilocus heterozygosity (MLH) estimates from 15 microsatellite markers to show evidence of heterozygosity fitness correlations (HFCs) in a long-distance migratory bird, the light-bellied Brent goose. We found significant, positive heterozygosity-heterozygosity correlations between random subsets of the markers we employed, and no evidence that a model containing all loci as individual predictors in a multiple regression explained significantly more variation than a model with MLH as a single predictor. Collectively, these results lend support to the hypothesis that the HFCs we have observed are a function of inbreeding depression. However, we do find that fitness correlations are only detectable in years where population level productivity is high enough for the reproductive asymmetry between high and low heterozygosity individuals to become apparent. We suggest that lack of evidence of heterozygosity-fitness correlations in animal systems may be because heterozygosity is a poor proxy measure of inbreeding, especially when employing low numbers of markers, but alternatively because the asymmetries between individuals of different heterozygosities may only be apparent when environmental effects on fitness are less pronounced. PMID- 21973193 TI - Genomic advances will herald new insights into the Brassica: Leptosphaeria maculans pathosystem. AB - The study of the relationship between plants and phytopathogenic fungi is one of the most rapidly moving fields in the plant sciences, the findings of which have contributed to the development of new strategies and technologies to protect crops. Plants employ sophisticated mechanisms to perceive and appropriately defend themselves against pathogens. A good example of plant and pathogen evolution is the gene-for-gene interaction between the fungal pathogen Leptosphaeria maculans, the causal agent of blackleg disease, and Brassica crops. This interaction has been studied at the genetic and physiological level due to its agro-economic importance. The newly available genome sequence for Brassica spp. and L. maculans will provide the resources to study the co-evolution of this plant and pathogen. Particularly, an understanding of the co-evolution of genes responsible for virulence and resistance will lead to improved plant protection strategies for Brassica canola and provide a model to understand plant-pathogen interactions in other major crops. This review summarises the research-to-date in the study of the Brassica-L. maculans gene-for-gene interaction, with a focus on the genetics of resistance in Brassica and the wealth of information to be gained from genome sequencing efforts. PMID- 21973194 TI - A randomized, observer-blinded, comparison of combined 1064-nm Q-switched neodymium-doped yttrium-aluminium-garnet laser plus 30% glycolic acid peel vs. laser monotherapy to treat melasma. AB - BACKGROUND: Melasma is a common pigmentary disorder that poses therapeutic challenges. Mixed-type melasma usually does not respond to conventional monotherapy. OBJECTIVE: To evaluate the effectiveness and safety of 1064-nm Q switched neodymium-doped yttrium-aluminium-garnet laser (1064 QNYL) and 30% glycolic acid (GA) peel in the treatment of melasma. METHODS: This was a split face study, in which 16 patients were treated with 1064 QNYL (6-mm spot size, 2.0 2.3 J/cm(2) fluence) for six sessions at 1-week intervals to the entire face, and with GA for three sessions at 2-week intervals to the experimental side of the face. Clinical evaluations, measurements on a pigment measuring device (Mexameter), and assessment of patient satisfaction and adverse events were performed at baseline and every visit. RESULTS: After treatment, significant improvements from baseline were seen in Mexameter and modified Melasma Area and Severity Index (mMASI) on both sides of the face. The combined therapy side achieved an average 32.6% improvement in Mexameter readings and 37.4% improvement in mMASI, compared with 22% and 16.7%, respectively, on the side treated with laser only (P <= 0.05). Both the physician and patient assessments correlated with the Mexameter results and mMASI. CONCLUSION: Combined 1064 QNYL and GA seems to be superior to 1064 QNYL alone in the treatment of mixed-type melasma. PMID- 21973196 TI - Elevated uric acid correlates with wound severity. AB - Chronic venous leg ulcers are a major health issue and represent an often overlooked area of biomedical research. Nevertheless, it is becoming increasingly evident that new approaches to enhance healing outcomes may arise through better understanding the processes involved in the formation of chronic wounds. We have for the first time shown that the terminal purine catabolite uric acid (UA) is elevated in wound fluid (WF) from chronic venous leg ulcers with relative concentrations correlating with wound chronicity. We have also shown a corresponding depletion in UA precursors, including adenosine, with increased wound severity. Further, we have shown that xanthine oxidase, the only enzyme in humans that catalyses the production of UA in conjunction with a burst of free radicals, is active in chronic WF. Taken together, this provides compelling evidence that xanthine oxidase may play a critical role in the formation of chronic wounds by prolonging the inflammatory process. PMID- 21973197 TI - Density functional theory studies on the structures and water-exchange reactions of aqueous Al(III)-oxalate complexes. AB - The structures and water-exchange reactions of aqueous aluminum-oxalate complexes are investigated using density functional theory. The present work includes (1) The structures of Al(C(2)O(4))(H(2)O)(4)(+) and Al(C(2)O(4))(2)(H(2)O)(2)(-) were optimized at the level of B3LYP/6-311+G(d,p). The geometries obtained suggest that the Al-OH(2) bond lengths trans to C(2)O(4)(2-) ligand in Al(C(2)O(4))(H(2)O)(4)(+) are much longer than the Al-OH(2) bond lengths cis to C(2)O(4)(2-). For Al(C(2)O(4))(2)(H(2)O)(2)(-), the close energies between cis and trans isomers imply the coexistence in aqueous solution. The (27)Al NMR and (13)C NMR chemical shifts computed with the consideration of sufficient solvent effect using HF GIAO method and 6-311+G(d,p) basis set are in agreement with the experimental values available, indicating the appropriateness of the applied models; (2) The water-exchange reactions of Al(III)-oxalate complexes were simulated at the same computational level. The results show that water exchange proceeds via dissociative pathway and the activation energy barriers are sensitive to the solvent effect. The energy barriers obtained indicate that the coordinated H(2)O cis to C(2)O(4)(2-) in Al(C(2)O(4))(H(2)O)(4)(+) is more labile than trans H(2)O. The water-exchange rate constants (k(ex)) of trans- and cis Al(C(2)O(4))(2)(H(2)O)(2)(-) were estimated by four methods and their respective characteristics were explored; (3) The significance of the study on the aqueous aluminum-oxalate complexes to environmental chemistry is discussed. The influences of ubiquitous organic ligands in environment on aluminum chemistry behavior can be elucidated by extending this study to a series of Al(III)-organic system. PMID- 21973198 TI - Blood glucose and subsequent cardiovascular disease: update of a meta-analysis. AB - BACKGROUND/PURPOSE: A 1999 meta-analysis described the relationship between blood glucose and subsequent cardiovascular events (MI, stroke, cardiovascular mortality). More studies have been published; therefore, we updated and refined estimates of this relationship in people without diabetes. ACCEPTABILITY CRITERIA: We accepted prospective studies that reported screening results for blood glucose levels (either fasting, 2-hour postprandial, 1-hour postprandial, or casual) divided into >=3 quantiles. Required data within each quantile were numbers exposed plus study duration or person-years at risk, and numbers of cardiovascular outcomes (myocardial infarction, stroke, death). No restrictions were placed on language or publication date. DATA SOURCES: Two reviewers searched Medline, Embase, Scopus, and Cochrane databases from inception until December 2009. Consensus settled discrepancies. DATA SYNTHESIS: Poisson regression quantified the relationship between glucose quantile and outcomes. Beta values were combined with inverse variance weightings using a random effects meta analytic model. RESULTS: We found 36 articles with 141 datasets examining the relationship between blood glucose (32 fasting, 52 2-hour postprandial, 37 1-hour postprandial, 20 casual) in 191,249 patients without diabetes (73% male) for 3 million person-years. There were 12,537 (6.6%) cardiovascular deaths, 14,445 (7.6%) cardiovascular events, 6862 (3.6%) cardiac and 3412 (1.7%) stroke deaths. Relative risks/unit increase in blood glucose were all significant for total cardiovascular events (RRs ranged from 1.09-1.51, all p-values < 0.005) and cardiovascular deaths (RR = 1.05-1.24, p < 0.007), and all for cardiac deaths (p < 0.05) except casual glucose; stroke mortality was less clear. The two strongest relationships were found between fasting levels and all events (RR = 1.51, CI: 1.20-1.89) and with cardiovascular mortality (RR = 1.40, CI: 1.18-1.60). With 2 hour postprandial levels, the respective RRs were 1.22 (1.17-1.28) and 1.24 (1.19 1.30). A limitation is the assumption of a continuous relationship between variables. CONCLUSIONS: We have provided refined estimates confirming the association between elevated blood glucose and subsequent cardiovascular events. PMID- 21973199 TI - Long-term safety and efficacy of fenofibrate/pravastatin combination therapy in high risk patients with mixed hyperlipidemia not controlled by pravastatin monotherapy. AB - OBJECTIVE: To assess the long-term safety and efficacy of a fenofibrate/pravastatin 160/40 mg fixed-dose combination in high-risk patients with mixed hyperlipidemia not controlled by pravastatin 40 mg monotherapy. STUDY DESIGN AND METHODS: After an 8-week pravastatin 40 mg and diet run-in period, high-risk patients (n = 248) with low-density lipoprotein cholesterol (LDL-C) >= 100 mg/dL and triglycerides (TG) >= 150 and <=400 mg/dL, were randomized to fenofibrate/pravastatin combination therapy or to pravastatin monotherapy for 12 weeks, followed by an open-label, 52-week safety phase on the combination therapy. RESULTS: Of the 224 patients who continued after the double-blind phase, 211 completed the one-year safety period. Overall, fenofibrate/pravastatin combination therapy was well tolerated during this extension study. Only three patients had an elevation of ALAT > 3 times the upper limit of normal and one patient a CPK elevation >=5, but <10 times the upper limit of normal. At week 64, and by comparison to baseline levels on pravastatin 40 mg, the fenofibrate/pravastatin combination therapy significantly reduced non-high density lipoprotein (non-HDL) cholesterol by 16.3%, LDL-C by 12.2%, TG by 31.6%, apolipoprotein B by 11.0% and increased HDL-cholesterol and apolipoprotein A1 respectively by 4.8 and 9.6% (p < 0.0001 for all the variables). A limitation of this trial is that the study was not powered to assess clinical events. CONCLUSIONS: Long-term co-administration of fenofibrate/pravastatin 160/40 mg in a single capsule was well tolerated and produced complementary benefits on the overall lipid profile of high-risk patients with mixed hyperlipidemia not controlled by pravastatin 40 mg. PMID- 21973200 TI - Fabrication of titanium dioxide and tungstophosphate nanocomposite films and their photocatalytic degradation for methyl orange. AB - Photocatalytic multilayer films with different numbers of bilayers were prepared via an electrostatic layer-by-layer (LbL) self-assembly method. These LbL films were characterized by UV-vis spectroscopy, atomic force microscopy (AFM), and X ray photoelectron spectroscopy (XPS). Our results indicate that TiO(2) and tungstophosphate (H(3)PW(12)O(40), abbreviated as PW(12)) are successfully incorporated into the thin films. The as-prepared (TiO(2)/PW(12))(n) films show good photocatalytic performance toward methyl orange (MO) solution at pH 2.0, which is attributed to the synergistic effect between TiO(2) and PW(12). The effect of experimental parameters including number of bilayers, initial concentration, and pH value of dye solution were also studied. The multilayer films can be easily recovered and reused several times with little change of degradation, indicating that they are stable under the ultraviolet (UV) irradiation. The detection of active species displays that active holes (h(+)) play a dominant role for MO photodegradation in the TiO(2)/PW(12) system. Taking advantage of immobilization of catalysts on glass slides, the problem of recovery is solved. It is expected that photocatalytic multilayer films have substantial applications in industry. PMID- 21973201 TI - Tinea faciei caused by Trichophyton verrucosum in a 20-month-old female: case report and summary of reported cases in Japan. PMID- 21973207 TI - Light activation of a cysteine protease inhibitor: caging of a peptidomimetic nitrile with Ru(II)(bpy)2. AB - A novel method for caging protease inhibitors is described. The complex [Ru(II)(bpy)(2)(1)(2)](PF(6))(2) (2) was prepared from the nitrile-based peptidomimetic inhibitor Ac-Phe-NHCH(2)CN (1). (1)H NMR, UV-vis, and IR spectroscopic and mass spectrometric data confirmed that 2 equiv of inhibitor 1 bind to Ru(II) through the nitrile functional group. Complex 2 shows excellent stability in aqueous solution in the dark and fast release of 1 upon irradiation with visible light. As a result of binding to the Ru(II) center, the nitriles of complex 2 are caged, and 2 does not act as a potent enzyme inhibitor. However, when 2 is irradiated, it releases 1, which inhibits the cysteine proteases papain and cathepsins B, K and L up to 2 times more potently than 1 alone. Ratios of the IC(50) values in the dark versus in the light ranged from 6:1 to 33:1 for inhibition by 2 against isolated enzymes and in human cell lysates, confirming that a high level of photoinduced enzyme inhibition can be obtained using this method. PMID- 21973209 TI - Nitric oxide as a critical factor for perception of UV-B irradiation by microtubules in Arabidopsis. AB - Influence of ultraviolet-B (UV-B) as an abiotic stress factor on plant microtubules (MTs) and involvement of nitric oxide (NO) as a secondary messenger mediating plant cell response to environmental stimuli were investigated in this study. Taking into account that endogenous NO content in plant cells has been shown to be increased under a broad range of abiotic stress factors, the effects of UV-B irradiation and also the combined action of UV-B and NO donor sodium nitroprusside (SNP) or NO scavenger 2-(4-carboxyphenyl)-4,4,5,5 tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO) on the MTs organization in different root cells of Arabidopsis thaliana were tested. Subsequently, realization of the MT-mediated processes such as root growth and development was studied under these conditions. Arabidopsis thaliana seedlings expressing the chimeric gene gfp-map4 were exposed to the enhanced UV-B with or without SNP or c PTIO pretreatment. The UV-B irradiation alone led to a dose-dependent root growth inhibition and to morphological alterations of the primary root manifested in their swelling and excessive root hair formation. Moreover, dose-dependent randomization and depolymerization of MTs in both epidermal and cortical cells under the enhanced UV-B were found. However, SNP pretreatment of the UV-B irradiated A. thaliana seedlings recovered the UV-B inhibited root growth as compared to c-PTIO pretreatment. It has been shown that in 24 h after UV-B irradiation the organization of MTs in root epidermal cells of SNP-pretreated A. thaliana seedlings was partially recovered, whereas in c-PTIO-pretreated ones the organization of MTs has not been distinctly improved. Therefore, we suppose that the enhanced NO levels in plant cells can protect MTs organization as well as MT related processes of root growth and development against disrupting effects of UV B. PMID- 21973210 TI - Type 2 diabetes mellitus interacts with obesity and common variations in PLTP to affect plasma phospholipid transfer protein activity. AB - BACKGROUND: Phospholipid transfer protein (PLTP) is an emerging cardiometabolic risk marker that is important in high-density lipoprotein (HDL) and triglyceride metabolism. Plasma PLTP activity is elevated in type 2 diabetes mellitus, whereas glucose may regulate PLTP gene transcription in vitro. Of interest, common PLTP variations that predict cardiovascular disease have been identified recently. We investigated whether the diabetic state is able to amplify relationships between obesity and PLTP gene variations with circulating PLTP levels. SUBJECTS AND METHODS: Plasma PLTP activity (using a phospholipid vesicles-HDL system), PLTP gene score [number of PLTP activity-decreasing alleles based on two tagging polymorphisms (rs378114 and rs60- 65904)] and waist circumference were determined in two Dutch cohorts comprising 237 patients with type 2 diabetes and 78 control subjects. RESULTS: Patients with diabetes were more obese (P < 0.001 for prevalence of increased waist circumference) and had 13% higher plasma PLTP activity (P < 0.001). PLTP gene score was not different in diabetic and control subjects (P = 0.40). PLTP activity was highest in patients with diabetes with an enlarged waist and lowest in control subjects with a normal waist circumference (P < 0.001). Multiple linear regression analysis revealed a positive interaction between diabetes status and waist circumference on PLTP activity (beta = 0.200, P = 0.005). Furthermore, diabetes status (beta = -0.485, P = 0.046) or HbA1c (beta = -0.240, P = 0.035) interacted with PLTP gene score to affect PLTP activity. CONCLUSIONS: Type 2 diabetes and enlarged waist circumference interact to impact on plasma PLTP activity. Diabetes may also amplify the association between plasma PLTP activity and common PLTP gene variations. Our findings support the hypothesis that diabetes-environment and diabetes-gene interactions govern plasma PLTP activity. PMID- 21973211 TI - Fluorodeoxyglucose positron emission tomography/computed tomography for evaluation of bone marrow involvement in lymphoma: when is it superior to biopsy? PMID- 21973212 TI - Role for p53 in selenium-induced senescence. AB - The tumor suppressor p53 and the ataxia-telangiectasia mutated (ATM) kinase play important roles in the senescence response to oncogene activation and DNA damage. It was previously shown that selenium-containing compounds can activate an ATM dependent senescence response in MRC-5 normal fibroblasts. Here, the shRNA knockdown approach and other DNA damage assays are employed to test the hypothesis that p53 plays a role in selenium-induced senescence. In MRC-5 cells treated with methylseleninic acid (MSeA, 0-10 MUM), depletion of p53 hampers senescence-associated expression of beta-galactosidase, disrupts the otherwise S and G2/M cell cycle arrest, desensitizes such cells to MSeA treatment, and increases genome instability. Pretreatment with KU55933, an ATM kinase inhibitor, or NU7026, an inhibitor of DNA-dependent protein kinase, desensitizes MSeA cytotoxicity in scrambled but not p53 shRNA MRC-5 cells. These results suggest that p53 is critical for senescence induction in the response of MRC-5 noncancerous cells to selenium compounds. PMID- 21973213 TI - Leaf cuticular n-alkanes as markers in the chemotaxonomy of the eggplant (Solanum melongena L.) and related species. AB - The complex of species formed by eggplant (Solanum melongena L.) and its wild and weedy relatives (mainly S. incanum L. and S. insanum L.) is characterised by an extreme morphological divergence that is not always associated with genetic variation. The taxonomy of so-called 'spiny Solanum' species (subgenus Leptostemonum) is therefore extremely unclear. Cultivated eggplant lacks resistance to pests that frequently occur among the wild forms and species. As these wild plants are a potential gene pool for improvement of eggplant cultivars, knowledge of the characteristics of taxonomic relations between plants of different origin is crucial. We suggest using the leaf cuticular n-alkane chain length distribution pattern as an alternative taxonomic marker for eggplant and related species. The results are in good agreement with current knowledge of the systematics of these plants; at the same time, the method developed here is useful for verifying plant identification based on morphological traits. Analysis of 13 eggplant cultivars, five accessions of S. incanum and two lines of S. macrocarpon enabled the intraspecific variation within eggplant to be assessed as low. There was wide variability among S. incanum accessions, probably because plants described as S. incanum are members of a number of different species. Some Asian accessions (sometimes described as S. insanum) were found to be almost identical to S. melongena, while a truly wild African S. incanum plant showed extensive similarity. The usefulness of the chemotaxonomic approach in dealing with the S. melongena-S. incanum complex is discussed. PMID- 21973214 TI - Exclusive conservation of mitochondrial group II intron nad4i548 among liverworts and its use for phylogenetic studies in this ancient plant clade. AB - Liverworts occupy a pivotal position in land plant (embryophyte) phylogeny as the presumed earliest-branching major clade, sister to all other land plants, including the mosses, hornworts, lycophytes, monilophytes and seed plants. Molecular support for this earliest dichotomy in land plant phylogeny comes from strikingly different occurrences of introns in mitochondrial genes distinguishing liverworts from all other embryophytes. Exceptionally, however, the nad5 gene- the mitochondrial locus hitherto used most widely to elucidate early land plant phylogeny--carries a group I type intron that is shared between liverworts and mosses. We here explored whether a group II intron, the other major type of organellar intron, would similarly be conserved in position across the entire diversity of extant liverworts and could be of use for phylogenetic analyses in this supposedly most ancient embryophyte clade. To this end, we investigated the nad4 gene as a candidate locus possibly featuring different introns in liverworts as opposed to the non-liverwort embryophyte (NLE) lineage. We indeed found group II intron nad4i548 universally conserved in a wide phylogenetic sampling of 55 liverwort taxa, confirming clade specificity and surprising evolutionary stability of plant mitochondrial introns. As expected, intron nad4i548g2 carries phylogenetic information in its variable sequences, which confirms and extends previous cladistic insights on liverwort evolution. We integrate the new nad4 data with those of the previously established mitochondrial nad5 and the chloroplast rbcL and rps4 genes and present a phylogeny based on the fused datasets. Notably, the phylogenetic analyses suggest a reconsideration of previous phylogenetic and taxonomic assignments for the genera Calycularia and Mylia and resolve a sister group relationship of Ptilidiales and Porellales. PMID- 21973215 TI - Problem of signal contamination in interhemispheric dual-sided subdural electrodes. AB - Dual-sided subdural electrodes are used in the localization and lateralization of seizure-onset zones when the area of interest is within the interhemispheric fissure. We designed the current study to test the validity of the assumption that each side of the dual-sided electrodes records from the hemisphere it faces. We recorded with dual-sided strip and grid electrodes implanted in the occipital interhemispheric space in two patients with nonoccipital epilepsy during two visual stimulation tasks in which subjects were presented with visual stimuli in the ipsilateral or contralateral visual hemifields. Our findings show substantial contamination of recordings from the opposite hemisphere. Although, as expected, electrodes recording through the falx record faintly from the contralateral cortical surface, they unexpectedly pick up strong signals from the cortex behind them. Therefore, we conclude that these electrodes should not be used for lateralization of the origin of epileptic activity or evoked responses. PMID- 21973216 TI - Development and stability of bacteriocin resistance in Campylobacter spp. AB - AIMS: Several bacteriocins (BCNs) that were identified from chicken commensal bacteria dramatically reduced Campylobacter colonization in poultry and are being directed toward on-farm control of this important foodborne human pathogen. A recent study has shown that BCN resistance in Campylobacter jejuni is very difficult to develop in vitro. In this study, in vivo development and stability of BCN resistance in Campylobacter was examined. METHODS AND RESULTS: Chickens infected with Camp. jejuni NCTC 11168 were treated with BCN E-760 at the dose of 5 mg kg(-1) body weight day(-1) via oral gavages for three consecutive days, which selected BCN-resistant (BCN(r)) mutants in the treated birds. However, all the in vivo-selected mutants only displayed low levels of resistance to BCN (MIC = 2-8 mg l(-1)) when compared to parent strain (MIC = 0.5 mg l(-1)). Inactivation of CmeABC efflux pump of the BCN(r) mutants led to increased susceptibility to BCN (8-32 fold MIC reduction). Three different BCN(r) Campylobacter strains (in vitro- or in vivo-derived) were examined for the stability of BCN resistance using both in vitro and in vivo systems. The low level of BCN resistance in these strains was not stable in vitro or in vivo in the absence of BCN selection pressure. CONCLUSIONS: Usage of BCN E-760 only selected low-level BCN(r) Camp. jejuni mutants in vivo, and the low-level BCN resistance was not stable in vitro and in vivo. SIGNIFICANCE AND IMPACT OF THE STUDY: The study provides helpful information for risk assessment of the future practical application of the anti Campylobacter BCNs in animals. PMID- 21973218 TI - Eccrine porocarcinoma arising within an area of Bowen disease. AB - Summary Very little is known about the aetiology of eccrine porocarcinoma (EP), a rare malignant sweat-gland tumour. Most reported cases have arisen de novo, or from a benign eccrine poroma. We report an unusual case, in which eccrine porocarcinoma arose at the exact site of pre-existing Bowen disease (BD). PMID- 21973217 TI - Pharmaceutical regulation of telomerase and its clinical potential. AB - Telomeres serve the dual function of protecting chromosomes from genomic instability as well as protecting the ends of chromosomes from DNA damage machinery. The enzyme responsible for telomere maintenance is telomerase, an enzyme capable of reverse transcription. Telomerase activity is typically limited to specific cell types. However, telomerase activation in somatic cells serves as a key step toward cell immortalization and cancer. Targeting telomerase serves as a potential cancer treatment with significant therapeutic benefits. Beyond targeting cancers by inhibiting telomerase, manipulating the regulation of telomerase may also provide therapeutic benefit to other ailments, such as those related to aging. This review will introduce human telomeres and telomerase and discuss pharmacological regulation of telomerase, including telomerase inhibitors and activators, and their use in human diseases. PMID- 21973219 TI - Expression characteristics of ARF1 and SAR1 during development and the de etiolation process. AB - ARF1 (ADP-ribosylation factor 1) and SAR1 (secretion-associated RAS super family) are involved in the formation and budding of vesicles throughout plant endomembrane systems. The molecular mechanisms of this transport have been studied extensively in mammalian and yeast cells. However, very little is known about the mechanisms of coat protein complex (COP) formation and recruitment of COP-vesicle cargoes in plants. To provide insights into vesicular trafficking in Pisum sativum L., we investigated mRNA and protein expression patterns of ARF1 and SAR1 in roots and shoots at early growth stages and in the de-etiolation process. We showed that ARF1 was concentrated mostly in the crude Golgi fractions, and SAR1 was concentrated predominantly in the crude ER fractions of de-etiolated shoots. ARF1 and SAR1 proteins were several times more abundant in shoots relative to roots. In total protein homogenates, the expression level of SAR1 and ARF1 was higher in shoots of dark-grown pea plants than light-grown plants. In contrast, ARF1 was higher in roots of light-grown pea relative to roots of dark-grown pea. With ageing, the ARF1 mRNA in roots was reduced, while SAR1 expression increased. Unlike ARF1 transcripts, ARF1 protein levels did not fluctuate significantly in root and shoot tissue during early development. The relative abundance of SAR1 protein in root tissues may suggest a high level of vesicular transport from the ER to the Golgi. Experimental results suggested that white light probably affects the regulation of ARF1 and SAR1 protein levels. On the other hand, short-term white light affects SAR1 but not ARF1. PMID- 21973220 TI - CYBA and GSTP1 variants associate with oxidative stress under hypobaric hypoxia as observed in high-altitude pulmonary oedema. AB - HAPE (high-altitude pulmonary oedema) is characterized by pulmonary hypertension, vasoconstriction and an imbalance in oxygen-sensing redox switches. Excess ROS (reactive oxygen species) contribute to endothelial damage under hypobaric hypoxia, hence the oxidative-stress-related genes CYBA (cytochrome b-245 alpha polypeptide) and GSTP1 (glutathione transferase Pi 1) are potential candidate genes for HAPE. In the present study, we investigated the polymorphisms -930A/G and H72Y (C/T) of CYBA and I105V (A/G) and A114V (C/T) of GSTP1, individually and in combination, in 150 HAPE-p (HAPE patients), 180 HAPE-r (HAPE-resistant lowland natives) and 180 HLs (healthy highland natives). 8-Iso-PGF2alpha (8-iso prostaglandin F2alpha) levels were determined in plasma and were correlated with individual alleles, genotype, haplotype and gene-gene interactions. The relative expression of CYBA and GSTP1 were determined in peripheral blood leucocytes. The genotype distribution of -930A/G, H72Y (C/T) and I105V (A/G) differed significantly in HAPE-p compared with HAPE-r and HLs (P<=0.01). The haplotypes G C of -930A/G and H72Y (C/T) in CYBA and G-C and G-T of I105V (A/G) and A114V (C/T) in GSTP1 were over-represented in HAPE-p; in contrast, haplotypes A-T of 930A/G and H72Y (C/T) in CYBA and A-C of I105V (A/G) and A114V (C/T) in GSTP1 were over-represented in HAPE-r and HLs. 8-Iso-PGF2alpha levels were significantly higher in HAPE-p and in HLs than in HAPE-r (P=2.2*10(-16) and 1.2*10(-14) respectively) and the expression of CYBA and GSTP1 varied differentially (P<0.05). Regression analysis showed that the risk alleles G, C, G and T of -930A/G, H72Y (C/T), I105V (A/G) and A114V (C/T) were associated with increased 8-iso-PGF2alpha levels (P<0.05). Interaction between the two genes revealed over-representation of most of the risk-allele-associated genotype combinations in HAPE-p and protective-allele-associated genotype combinations in HLs. In conclusion, the risk alleles of CYBA and GSTP1, their haplotypes and gene gene interactions are associated with imbalanced oxidative stress and, thereby, with high-altitude adaptation and mal-adaptation. PMID- 21973221 TI - Analysis of the potential role of Apolipoprotein E polymorphism in genetic predisposition to spontaneous abortion. AB - PROBLEM: Up to 20% of pregnancies end in the first trimester by spontaneous abortion, but a significant number remains unexplained. The aim of this study is to investigate the role of variants within the gene for apolipoprotein E (APOE) in the genetic determination of spontaneous abortions. METHOD OF STUDY: We collected DNA from 410 tissue samples of spontaneous abortions, and APOE was genotyped by PCR-RFLP method. The frequencies were compared with a population sample of adults (N = 2606) and with a positive control (1060 women with at least two children). RESULTS: The frequencies of the APOE genotypes in abortions (APOE2E2 + E3E2 = 0.132; APOE3E3 = 0.661; APOE3E4 + E4E4 = 0.195; APOE4E2 = 0.012) did not significantly differ (P = 0.604) from the frequencies in analyzed adult population study (APOE2E2 + E3E2 = 0.132; APOE3E3 = 0.686; APOE3E4 + E4E4 = 0.169; APOE4E2 = 0.014) or from the positive control (APOE2E2 + E3E2 = 0.133; APOE3E3 = 0.691; APOE3E4 + E4E4 =0.166; APOE4E2 = 0.010; P = 0.592). CONCLUSION: Our study suggests that APOE may not be associated with spontaneous abortions in Caucasians. PMID- 21973222 TI - European quality assurance programme in rectal cancer--are we ready to launch? AB - AIM: There have been initiatives to create a European audit project. This paper addresses the issue of differences in data collected by different registries. METHOD: Patients with rectal cancer treated in 2008 and recorded in quality registries from Belgium, Germany/Poland, Spain and Sweden were analyzed. The comparison included number of patients, gender, age, American Society of Anesthesiology (ASA) classification, preoperative diagnostic and staging procedures, neoadjuvant therapy, surgical treatment and quality of surgery, postoperative complications and adjuvant treatment. RESULTS: The Belgian database consisted of 622 patients, the German/Polish database consisted of 3,393 patients, the Spanish database consisted of 1,641 patients and the Swedish database consisted of 1,826 patients. The percentage of patients in each ASA stage was highly variable. MRI use was highest in Spain and Sweden and very low in Germany/Poland. The percentage of cT4 stage tumours in Sweden was much higher than in all other countries. Sweden recorded the highest percentage of primary metastatic disease (20.3%) and Belgium recorded the lowest (10.2%). Neoadjuvant therapy in different protocols was administered to 41.2% patients in Germany/Poland, to 50.8% in Spain, to 55.2% in Belgium and to 62% in Sweden. Laparoscopic surgery (conversion rate) was performed for cure in 5% (28%) of patients in Sweden, in 20.8% (20.6%) in Spain, in 28.6% (15.2%) in Belgium and in 14.5% (8.9%) in Germany/Poland. The 30-day mortality for anterior resection, abdominoperineal excision and Hartmann's procedure in Sweden, Belgium and Spain was 2.0%, 2.3% and 3.1%, respectively. The German/Polish database reported an in hospital mortality of 3.2%. CONCLUSION: A European quality assurance project in rectal cancer is possible only after data collection is standardized. PMID- 21973223 TI - Histochemical screening, metabolite profiling and expression analysis reveal Rosaceae roots as the site of flavan-3-ol biosynthesis. AB - Histochemical screening of 30 Rosaceae genera representing all classic subfamilies demonstrated flavan-3-ols (catechins) as general secondary metabolites in roots of Rosaceae. Semi-quantitative LC-MS analyses confirmed the presence of catechin, epicatechin and various dimeric flavan-3-ols (also representing higher polymeric proanthocyanidins) as prominent polyphenols in root tips of Fragaria (strawberry), Malus (apple), Rosa (rose), Pyrus (pear) and Prunus (plum). Distinct patterns of flavan-3-ol distribution at the cellular level were found in strawberry (Fragaria * ananassa) and apple (Malus * domestica) root tips. The calyptras (root caps) showed the most prominent flavan 3-ol staining for these two genera. Border cells of Fragaria and Malus, as first demonstrated here for Rosaceae, were also found to contain flavan-3-ols. Transcript analyses with cDNA demonstrated root expression of known flavonoid genes expressed in the respective fruits and leaves. Primarily, this proves in situ biosynthesis of flavan-3-ols in these roots. Knowledge of the distinct cellular distribution patterns and their in situ biosynthesis in roots provides a basis for analysis of the functional roles of Rosaceae root flavan-3-ols. PMID- 21973224 TI - Effect of time, temperature, and kinetics on the hysteretic adsorption-desorption of H2, Ar, and N2 in the metal-organic framework Zn2(bpdc)2(bpee). AB - The intriguing hysteretic adsorption-desorption behavior of certain microporous metal-organic frameworks (MMOFs) has received considerable attention and is often associated with a gate-opening (GO) effect. Here, the hysteretic adsorption of N(2) and Ar to Zn(2)(bpdc)(2)(bpee) (bpdc = 4,4'-biphenyldicarboxylate; bpee = 1,2-bipyridylethene) shows a pronounced effect of allowed experimental time at 77 and 87 K. When the time allowed is on the order of minutes for N(2) at 77 K, no adsorption is observed, whereas times in excess of 60 h is required to achieve appreciable adsorption up to a limiting total coverage. Given sufficient time, the total uptake for N(2) and Ar converged at similar reduced temperatures, but the adsorption of Ar was significantly more rapid than that of N(2), an observation that can be described by activated configurational diffusion. N(2) and Ar both exhibited discontinuous stepped adsorption isotherms with significant hysteresis, features that were dependent upon the allowed time. The uptake of H(2) at 77 K was greater than for both N(2) and Ar but showed no discontinuity in the isotherm, and hysteretic effects were much less pronounced. N(2) and Ar adsorption data can be described by an activated diffusion process, with characteristic times leading to activation energies of 6.7 and 12 kJ/mol. Fits of H(2) adsorption data led to activation energies in the range 2-7 kJ/mol at low coverage and nonactivated diffusion at higher coverage. An alternate concentration-dependent diffusion model is presented to describe the stepwise adsorption behavior, which is observed for N(2) and Ar but not for H(2). Equilibrium is approached very slowly for adsorption to molecularly sized pores at low temperature, and structural change (gate opening), although it may occur, is not required to explain the observations. PMID- 21973225 TI - Total synthesis of norcembrenolide B and scabrolide D. AB - An efficient stereoselective synthesis of norcembrenolide B (8) and scabrolide D (9) is reported. The strategy is inspired by biogenetic relationships of related cembrenoids. Central to this approach is the construction of norbipinnatin J which upon selective C2 deoxygenation and C8 oxygenation produces norrubifolide and norcoralloidolide A. A sequence of site-selective oxidations and skeletal reorganizations then yields, in a divergent manner, compounds 8 and 9. The studies allow revision of the proposed structure of scabrolide D (9), which is identical to norcembrenolide C. PMID- 21973226 TI - Where to with treatment for ADHD? PMID- 21973227 TI - Adult ADHD: prevalence of diagnosis in a US population with employer health insurance. AB - OBJECTIVE: The burden of attention-deficit/hyperactivity disorder (ADHD) in adults is increasingly recognized. This retrospective analysis was designed to estimate the prevalence of diagnosed ADHD in a population of insured, employed individuals and their dependents in the United States. METHODS: Health care claims data obtained from the MarketScan Commercial Claims and Encounters Database were analyzed. Patients with ADHD were identified by at least two diagnostic claims per calendar year. Once identified, patient records were examined for evidence of continuing ADHD. RESULTS: Between 2002 and 2007, the MarketScan database identified 342,284 patients with more than one claim for ADHD. Of these, 79,368 patients met the eligibility for the prevalence estimates. During the study period, the prevalence of diagnosed ADHD among adults increased more than three-fold: 1.24 to 4.02 cases per 1000 covered members. The largest proportion of cases was in the 18-24 years age group (42.8%-45.8% per year). Most cases were males; however, the ratio of females-to-males diagnosed increased over time. ADHD with hyperactivity was prevalent across all age groups analyzed, although more common in the 18-24 years group. Pharmacy claims showed patients receiving medical treatment for ADHD increased from 78% to 88.5%. A limitation of this study is that it is restricted to employed persons and their dependents. Thus, the results from this database may underestimate the true prevalence of diagnosed ADHD in the US population. CONCLUSIONS: While the claims database used included employed insured persons and dependents only, study results highlight the rising prevalence of diagnosed ADHD in a US adult population. The prevalence increased more than three-fold from 2002 to 2007 with the largest increase in the 18-24 years age group. These findings on ADHD prevalence highlight the need for greater attention to the medical treatment of this disorder in different age groups, particularly in young adults. PMID- 21973228 TI - ADHD medication use, adherence, persistence and cost among Texas Medicaid children. AB - OBJECTIVES: (1) Describe ADHD medication use, adherence and persistence. (2) Determine factors (e.g., medication type, demographics, concomitant medication use) associated with ADHD medication adherence and persistence. (3) Compare ADHD medication costs. METHODS: Continuously enrolled Texas Medicaid children (3-18 years) with >= 2 ADHD prescription claims (July 2002-December 2008) were included. Prescription claims were grouped by medication type (i.e., immediate release, extended-release, prodrug, non-stimulant); medication class (i.e., stimulant, non-stimulant); and duration of action (i.e., long-acting, short acting). Adherence, using medication possession ratio, was measured continuously and dichotomously (80% cut-off). Persistence was days of continuous therapy without a 30-day gap and medication costs were reimbursement amount paid to dispensing pharmacies. RESULTS: The study sample (n = 62,789) was primarily 6-12 years (61.7%) and male (69.2%). The majority of the subjects were prescribed extended-release agents (70.3%), stimulant agents (86.4%), and long-acting agents (84.5%). Adherence and persistence (adherence mean +/- SD; adherence dichotomous; persistence mean +/- SD) varied among medication type and was highest for non stimulants (52.5 +/- 30.9; 25.8%; 153.3 +/- 124.3), followed by extended-release stimulants (52.1 +/- 30.2; 24.1%; 143.7 +/- 120.8), prodrug stimulants (47.6 +/- 30.9; 21.1%; 113.3 +/- 100.5) and immediate-release stimulants (37.2 +/- 27.1; 9.8%; 95.4 +/- 92.6). Logistic regression showed immediate-release stimulant users were 67% less adherent than non-stimulant users (p < 0.0001) and linear regression showed immediate-release, extended-release and long-acting users (p < 0.0001) were significantly less persistent than non-stimulant users. Females, increase in total number of medications, and comorbid medications were associated with better adherence and persistence. Non-stimulant agents ($4.04 +/- $2.15) had the highest mean medication cost per patient per day and immediate-release stimulants had the lowest ($1.24 +/- $0.97). CONCLUSIONS: ADHD medication adherence and persistence was suboptimal. Although there was no difference in adherence between long-acting stimulant and non-stimulant users, non-stimulant users were more persistent compared to stimulant users. This study was limited due to the use of retrospective prescription claims data, which cannot capture actual patient use patterns, ICD-9 diagnoses, family history and support, or side effect profiles. Because ADHD can be effectively treated with pharmacotherapy, providers should be proactive in identifying patients with poor adherence and intervene to address barriers to medication adherence and persistence. PMID- 21973229 TI - Clinical utility of ADHD symptom thresholds to assess normalization of executive function with lisdexamfetamine dimesylate treatment in adults. AB - OBJECTIVES: This analysis assessed the relationship of various cutoff scores of the ADHD Rating Scale IV (ADHD-RS-IV) to levels of improvement in ADHD-related executive function (EF), measured by the Brown ADD Scale for Adults (BADDS), which may provide a measure of clinically meaningful EF improvement after ADHD treatment. METHODS: Post hoc analysis of a 4-week, open-label, dose-optimization phase in a double-blind, placebo-controlled study of lisdexamfetamine dimesylate (LDX) in adults with ADHD. The BADDS for Adults, a validated, normed, self-report measure of EF in ADHD, provides a qualitative measure to rate treatment progress. The ADHD-RS-IV assesses current symptom status based on DSM-IV criteria. Postbaseline ADHD-RS-IV scores were categorized according to four cutoff criteria of symptom remission: (1) ADHD-RS-IV total score <= 18; (2) ADHD-RS-IV total score <= 10; (3) no ADHD-RS-IV item scored >1; and (4) ADHD-RS-IV total score <= 18 and <= 2 items per subscale with a score of 2. Sensitivity and specificity of criteria for identifying participants with optimal BADDS scores were assessed using receiver operating characteristics (ROC). Safety evaluation included treatment-emergent adverse events (TEAEs). RESULTS: At endpoint, 85/127 participants had optimal BADDS scores. Linear ANOVA indicated limited overlap between BADDS and ADHD-RS-IV scores (r (2) = 0.20; P < 0.0001). Specificity was similar for criteria 1-4 (0.46, 0.39, 0.39, and 0.42), as were ROC (0.699, 0.776, 0.732, and 0.668). Sensitivity was high for criteria 2 and 3 (0.96, 0.92), lower for criteria 1 and 4 (0.72, 0.75). TEAEs were consistent with those of stimulants. CONCLUSION: Criteria 2 and 3 had satisfactorily high sensitivity, but no criteria had adequate specificity. AUC comparison indicated that criteria 2 and 3 ADHD-RS-IV thresholds may be more accurate assessments of EF normalization as measured by the BADDS. The open-label design, small sample size, and selection criteria limit the applicability of these results to a larger treatment population. PMID- 21973230 TI - Effect of atomoxetine on Tanner stage sexual development in children and adolescents with attention deficit/hyperactivity disorder: 18-month results from a double-blind, placebo-controlled trial. AB - OBJECTIVE: To determine the effects of long-term atomoxetine treatment on sexual development in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) as compared with placebo and with a national US survey in non Hispanic white children and adolescents. METHODS: This double-blind, placebo controlled, relapse prevention, multicenter trial was conducted in pediatric patients (6-15 years) with DSM-IV diagnosed ADHD and lasting for ~ 18 months. All patients received 10 weeks of open-label atomoxetine treatment (0.5-1.8 mg/kg/day). Patients responding in the last 2 weeks of treatment were randomized to double-blind treatment with either placebo or atomoxetine for up to 9 months, after which atomoxetine patients were re-randomized to either continued atomoxetine treatment or to placebo for up to another 6 months. Patients randomized to placebo at first randomization remained on placebo. The Tanner stage was assessed by the investigator at baseline and at approximately 6, 12, and 18 months, and the rate of sexual development (change in the Tanner stage) was compared between treatment groups. RESULTS: No statistically significant differences were observed between treatment groups either in sexual development (mean time, in days, to the first Tanner stage change: atomoxetine, 464.3 +/- 23.0; placebo, 433.1 +/- 14.4; p = 0.33) or in the duration of treatment exposure (atomoxetine, 315.3 days; placebo, 315.1 days; p = 0.90). Similar proportions of patients had at least one Tanner stage increase (atomoxetine: 27.1%; placebo: 31.9%; p = 0.39). Proportions of patients in each baseline Tanner stage group moving to higher stages were not statistically significantly different (p = 0.88, p = 0.18, p > 0.99, p = 0.68 for baseline Tanner stages 1-4, respectively). The puberty onset age was similar across treatment groups and consistent with US normative data. CONCLUSIONS: Long-term atomoxetine treatment was not associated with any appreciable impact on or delay in sexual maturation in children with ADHD compared with US normative data. LIMITATIONS: Study limitations include the relatively short duration of exposure to atomoxetine treatment, and the fact that half of the patients had been previously treated with stimulants. In addition, the Tanner stage data were collected as a secondary measure. PMID- 21973231 TI - Treatment outcomes with methylphenidate formulations among patients with ADHD: retrospective claims analysis of a managed care population. AB - OBJECTIVE: Describe treatment patterns, resource use, and predictors of methylphenidate (MPH) switch among children (6-12 years), adolescents (13-17 years), and adults (>= 18 years) with attention-deficit/hyperactivity disorder (ADHD). METHODS: This retrospective U.S. managed care database study used medical, pharmacy, and enrollment data to examine treatment patterns among patients with >= 1 ADHD diagnosis code (ICD-9 314.00-314.9), MPH pharmacy claims during 01/01/2004-09/30/2006, and no ADHD pharmacy claims in prior 6 months. Patients were followed for 1 year for dosage change, switch (change to non-MPH treatment), augmentation, persistence (number days on index medication) and adherence (days supplied/days persistent). End points were assessed by age group and MPH formulation. Cox proportional hazards modeling was conducted to determine predictors of MPH switch. RESULTS: Among 23,860 MPH users, 51.4% had a dosing change, 14% switched to a non-MPH agent, and 4% augmented MPH therapy. Among those prescribed long-acting (LA) MPH (N = 14,681), switching rates were 14% for children, 13% for adolescents, and 16% for adults. Augmentation rates for LA MPH were <5%. Overall, 53% of patients were adherent with mean persistence of 219 days. For the subgroup of patients prescribed LA MPH (n = 14,681), adherence ranged from 49% (adolescents) to 59% (children); persistence varied between 183 days (adults) to 256 days (children). During the 1-year follow-up, office/clinic visits were the major driver of health care resource use in MPH patients (mean 9.7 visits/patient). Patients with psychiatric comorbidity utilized significantly greater services. Predictors of MPH switch included psychiatric comorbidity (hazards ratio [HR] 1.37; 95% confidence interval [CI] = 1.26-1.48; p < 0.0001) and specialty prescribers (HR 1.19, 95% CI = 1.04-1.35; p = 0.011). Potential limitations of this study include use of claims data for definition of drug usage; inclusion of medications approved for use in ADHD; assessment of switching that may not have captured short-term augmentation; absence of economic, clinical and other variables from the claims dataset that may have influenced treatment selection, and outcomes. The 6-month baseline period to determine newly treated patients may not guarantee exclusion of all previously treated patients who restart therapy after an extended period. CONCLUSIONS: Children exhibited the highest persistence of MPH users. ADHD patients on MPH therapy with a psychiatric comorbidity may require additional follow-up to help improve adherence and reduce health care resource use. PMID- 21973232 TI - Variations in serum 25-hydroxyvitamin D during acute pancreatitis: an exploratory longitudinal study. AB - OBJECTIVES: We tested the hypothesis that 25-hydroxyvitamin D3 (25OHD) changes during acute inflammation in humans. METHODS: Patients with first episode of acute pancreatitis were included. Blood samples were acquired on admission and on days 1, 2, and 14. RESULTS: In total, 73 patients (35 males, median age 59) entered the study. On admission, the distribution of 25-OHD levels was as follows: severely deficient (<13 nmol/L) 23%; deficient (13-25 nmol/L) 20%; insufficient (26-50 nmol/L) 40%; and normal (<50 nmol/L) 17%. There was a significant fall and linear trend in 25OHD, albumin, and hemoglobin from day 0 to day 2. From day 0 to day 2 the drop in 25OHD was 3.1 nmol/L (95% CI 0.59-5.63). The changes from day 0 to day 2 in 25OHD were associated with changes in C reactive protein (p = 0.02) but not with leukocyte or monocyte count. CONCLUSIONS: The 25OHD levels dropped during the first 2 days of acute pancreatitis beyond what was expected based on 25OHD half-life. This study supports our hypothesis that an acute inflammatory condition utilizes 25OHD, but other mechanisms could interfere. PMID- 21973233 TI - Serum FGF-21 levels in type 2 diabetic patients. AB - BACKGROUND: Fibroblast growth factor (FGF)-21 has been recently characterized as a potent metabolic regulator, but the physiological role of FGF-21 remains poorly understood. This study was designed to investigate serum FGF-21 levels in type 2 diabetes mellitus (T2DM) patients and explore the correlations between its serum levels and various cardiometabolic parameters in humans. METHODS: Fifty-four newly diagnosed patients with T2DM (NDDM), 54 subjects with long duration of T2DM (LDDM), that is, more than 5 years, and 35 normal controls participated in this study. Fasting serum FGF-21 levels were measured using ELISA kits. The anthropometric parameters, glucose, glycosylated hemoglobin A1c, lipids, insulin, and high-sensitive C-reactive protein (hsCRP) levels were also measured in fasting status. RESULTS: Serum FGF-21 levels were significantly higher in patients with NDDM and LDDM than in controls (361.80 +/- 140.28 pg/mL and 351.17 +/- 133.44 pg/mL vs. 185.89 +/- 59.29 pg/mL, both p < 0.01), but there was no difference in serum FGF-21 levels between NDDM and LDDM. Fasting serum FGF-21 was found to correlate positively and significantly with age, waist-to-hip ratio, systolic blood pressure, fasting plasma glucose, glycosylated hemoglobin A1c, homeostasis model assessment (HOMA) of insulin resistance, and hsCRP, but negatively with HOMA of beta-cell insulin secretion. Furthermore, multiple regression analyses showed that fasting insulin, HOMA of insulin resistance, low density lipoprotein cholesterol, and hsCRP were independent factors influencing serum FGF-21 levels. Logistic regression analyses demonstrated that serum FGF-21 was significantly associated with T2DM. CONCLUSIONS: Serum FGF-21 levels were significantly increased in patients with T2DM. They may play a role in the pathogenesis of T2DM. PMID- 21973234 TI - Anti-proliferative effect and action mechanism of dexamethasone in human medullary thyroid cancer cell line. AB - INTRODUCTION: Dexamethasone is known to inhibit the cell proliferation of certain transformed cell lines. In this study, the effect and action mechanism of dexamethasone were examined in the human medullary thyroid cancer cell line, TT cells. METHODS: TT cells were treated with or without dexamethasone. 5-Bromo-2' deoxyuridine uptake assay was used to evaluate cell proliferation. Cell cycle and its regulatory proteins were assessed by flow cytometry and western blot analysis, respectively. Apoptosis was analyzed by Hoechst staining and Annexin V assay. RESULTS: Dexamethasone significantly reduced TT cell proliferation by 60% (p < 0.01). A substantial portion of cells was arrested at the G1 phase. The expression levels of cyclin D1, cyclin-dependent kinase (CDK)4, and CDK2 were decreased. In addition, the phosphorylation of retinoblastoma protein, which is a critical checkpoint protein in the transition of G1 to S phase, was decreased. On the other hand, the expression level of p27(Kip1), which is a cyclin/CDK inhibitor, was enhanced. Hoechst staining showed many fragmented nuclei in the dexamethasone-treated cells. The proportion of early apoptotic cells was also increased in the Annexin V assay. CONCLUSION: Dexamethasone inhibited the proliferation of TT cells through cell cycle arrest at the G1 phase and increased apoptosis. PMID- 21973235 TI - Human obesity reduces the number of hepatic leptin receptor (ob-R) expressing NK cells. AB - OBJECTIVE: In the industrialized world, obesity is an increasing socioeconomic health problem. Obese subjects have a higher risk of developing several types of cancer. NK cells are an integral component of the innate immune system, able to destruct tumor cells. The adipokine leptin plays a crucial role in the development of obesity and its related diseases. Peripheral leptin signaling is modulated by the liver. METHODS: The aim of this study was to evaluate the number of hepatic NK cells (CD56+) and the number of leptin-receptor positive (Ob-R+) cells in the livers of five normal-weight and five obese humans. Livers were removed during autopsy and accurately defined sections were stained immunohistochemically and CD56+, Ob-R+, and double-positive cells were quantified. RESULTS: Results revealed a dramatic reduction of NK cells and Ob-R expressing NK cells in the livers of obese individuals. CONCLUSIONS: The present study demonstrates, for the first time, body-weight-dependent numbers of hepatic NK cells. This supports the hypothesis of obesity-associated alterations of immune cell numbers in different human organs. PMID- 21973236 TI - Insulin resistance in nodular thyroid disease. AB - BACKGROUND: Insulin had been shown to have a mitogenic effect on thyroid cell cultures. The aim of this study was to investigate insulin resistance in patients with euthyroid nodular goiter. METHODS: Sixty-three patients with nodular thyroid disease and 83 healthy controls were included in the study. Both the patient and the control group were euthyroid, euglycemic and normotensive. None of the study subjects had risk factors for insulin resistance. All the study subjects were evaluated by serum insulin levels and biochemical parameters and thyroid ultrasound. All subjects with thyroid nodules greater than 1cm (n = 36) were offered to undergo thyroid fine needle aspiration biopsy. RESULTS: The two groups were similar with respect to age, gender, BMI, waist circumference, serum lipid levels, serum fT3, fT4 and TSH levels. But HOMA was found to be significantly higher in the patient group (p: 0.007) and thyroid volume was significantly greater in the patient group (p = 0.03). In the patient group there was a significant correlation between HOMA and nodule volume (p < 0.001) while there was not a significant correlation between HOMA and number of thyroid nodules. Thyroid cancer was diagnosed in 3 of the 36 patients (8.33 %). CONCLUSIONS: Insulin resistance may induce increased thyroid proliferation and nodule volume and nodule formation. Therefore, insulin resistance may be a risk factor for euthyoid nodular goiter. PMID- 21973237 TI - Current status of leprosy: epidemiology, basic science and clinical perspectives. AB - Leprosy has affected humans for millennia and remains an important health problem worldwide, as evidenced by nearly 250 000 new cases detected every year. It is a chronic infectious disorder, caused by Mycobacterium leprae, that primarily affects the skin and peripheral nerves. Recent advances in basic science have improved our knowledge of the disease. Variation in the cellular immune response is the basis of a range of clinical manifestations. The introduction of multidrug therapy has significantly contributed to a decrease in the prevalence of the disease. However, leprosy control activities, including monitoring and prevention programs, must be maintained. PMID- 21973238 TI - Slow-cycling therapy-resistant cancer cells. AB - Tumor recurrence after chemotherapy is a major cause of patient morbidity and mortality. Recurrences are thought to be secondary to small subsets of cancer cells that are better able to survive traditional forms of chemotherapy and thus drive tumor regrowth. The ability to isolate and better characterize these therapy-resistant cells is critical for the future development of targeted therapies aimed at achieving more robust and long-lasting responses. Using a novel application for the proliferation marker carboxyfluorescein diacetate, succinimidyl ester (CFSE), we have identified a population of slow-cycling, label retaining tumor cells in both in vitro sphere cultures and in vivo xenograft models. Strikingly, label-retaining cells exhibit a multifold increase in ability to survive traditional forms of chemotherapy and reenter the cell cycle. Further, we demonstrate the innovative application of CFSE to live sort slow-cycling tumor cells and validate their chemoresistance and tumorigenic potential. PMID- 21973239 TI - Complex interactions between molecular ions in solution and their effect on protein stability. AB - Protein stability in ionic solutions depends on the delicate balance between protein-ion and ion-ion interactions. For molecular ions containing multiple charged groups, the role of ion-ion interactions is particularly important. In this study, we show how the interplay between homo- and heteroion pairing influences protein stability using polyarginine salts as a model system. For the chloride salts, protein thermostability decreases as the size of the peptide increases, indicating enhanced binding to the protein. Moreover, it indicates reduced homoion pairing between Gdm(+) and carboxylate groups that is largely responsible for aggregation suppression, rather than denaturation, in monomeric arginine solutions. However, for the sulfate salts, strong heteroion pairing between the Gdm(+) groups and the sulfate counterions compensates for the loss of homoion pairing and, in return, leads to enhanced thermostability and a dramatically reduced (up to 10-30 times) rate of protein aggregation. Molecular dynamics simulations reveal how this ion pairing enhances conformational stability and, at the same time, reduces protein association. This study provides insight into complex ion effects on protein stability and serves as an example of how these intrasolvent interactions can be leveraged to enhance protein stability. PMID- 21973240 TI - Association of genetic variations in mTOR with risk of childhood acute lymphoblastic leukemia in a Chinese population. AB - The mammalian target of rapamycin (mTOR) is an important protein kinase regulating cell survival and apoptosis. To determine whether genetic variations in mTOR are associated with risk of acute lymphoblastic leukemia (ALL) in Chinese children, we genotyped two tag single nucleotide poymorphisms (SNPs) in mTOR (rs2536 and rs2295080) in a case-control study. We observed that the variant genotype TC of mTOR rs2536 was associated with a significantly decreased risk of childhood ALL (adjusted odds ratio [OR] = 0.67, 95% confidence interval [CI] = 0.46-0.96), and the association was more pronounced in high-risk ALL and T phenotype ALL groups. Additionally, we found that the combined genotypes TC/CC decreased the risk of ALL only in the high-risk ALL group (adjusted OR = 0.54, 95% CI = 0.32-0.91) and T-phenotype ALL group (adjusted OR = 0.29, 95% CI = 0.10 0.84). These results suggest that the mTOR rs2536 polymorphism is involved in the susceptibility to childhood ALL in a Chinese population. PMID- 21973242 TI - Moral standards and scientific integrity in journal editorship. PMID- 21973241 TI - Twenty-four-hour profiles of plasma glucose, insulin, C-peptide and free fatty acid in subjects with varying degrees of glucose tolerance following short-term, medium-dose prednisone (20 mg/day) treatment: evidence for differing effects on insulin secretion and action. AB - OBJECTIVE: To determine the time course and prandial effects of short-term, medium-dose prednisone on 24-h metabolic patterns under standardized conditions. CONTEXT: Glucocorticoids (GCs) adversely affect glucose homoeostasis but 24-h profiles of glucose, insulin, C-peptide and free fatty acids (FFAs) following short-term, medium-dose prednisone treatment in persons with varying degrees of glucose tolerance are not well defined. DESIGN: An open-label cross-sectional interventional study. SUBJECTS: Three groups were prospectively studied: persons with type 2 diabetes (T2DM; n = 7), persons 'at risk' for T2DM (AR; n = 8) and persons with normal glucose tolerance (NGT; n = 5). METHODS: Before and after 3 day treatment with prednisone 20 mg each morning, subjects underwent 24-h frequent blood sampling. Eucaloric mixed meals were provided at 08:00, 12:00 and 18:00 h. Insulin/glucose ratio provided an estimate of beta-cell response to meal stimuli. MEASUREMENTS: Plasma glucose, insulin, C-peptide, haemoglobin A1c and FFA. RESULTS: Prednisone induced greater increases in glucose levels from midday (P = 0.001) to midnight (P = 0.02) in the T2DM than the AR and NGT groups. In contrast, insulin (P = 0.03) and C-peptide (P = 0.04) levels decreased postbreakfast in the T2DM group, whereas no changes in the morning but higher C peptide levels (P = 0.03) from midday to midnight were observed in the AR group. In the T2DM group, insulin/glucose ratio decreased postbreakfast (P = 0.04) and increased postdinner (P = 0.03). Fasting glucose, insulin and C-peptide levels were unchanged in all groups, and FFA levels modestly increased postdinner (P = 0.03) in the NGT group. CONCLUSION: Short-term, medium-dose prednisone treatment induces postprandial hyperglycaemia in T2DM and AR predominantly from midday to midnight because of suppression of insulin secretion followed by decreased insulin action that dissipates overnight. Effective treatment of prednisone induced hyperglycaemia should target both rapid onset relative insulin deficiency and a less than 24-h total duration of effect. PMID- 21973244 TI - From Norm to Eric: avoiding lifestyle drift in Australian health policy. PMID- 21973245 TI - Smoking during pregnancy--need for consistent public health data in Australia. PMID- 21973246 TI - Iodine status in Melbourne adults in the early 1990s and 2007-08. AB - OBJECTIVE: To investigate the iodine status of Melbourne adults in 1992-94 and 2007-08, and to assess dietary iodine intake to enable comparison with recommended Nutrient Reference Values. METHOD: A cross-sectional study utilising 24-hr urine samples collected at two time points in a random sample of the Melbourne Collaborative Cohort Study. Two hundred and fifty seven adults (128 males, 129 females) in 1992-94, with a mean age of 56 years, and 265 adults (132 males, 133 females) in 2007-08, with a mean age of 68 years, were assessed, all being Melbourne residents. Urinary iodine concentration (UIC) was determined and daily urinary iodine excretion and daily iodine intake were assessed. RESULTS: In 1992-94, the median UIC was 27 MUg/L and 84% had UIC <50 MUg/L. The median daily iodine intake was 51 MUg/d, and 83% of participants had dietary iodine intakes below the Estimated Average Requirement of 100 MUg/d. In 2007-08, the median UIC was 49 MUg/L, 51% had UIC <50 MUg/L and the median daily iodine intake was 98 MUg/d, with 52% of intakes below the EAR. CONCLUSION: Melbourne adults were moderately iodine deficient in 1992-94, and borderline moderately deficient in 2007-08. IMPLICATIONS: While iodine status appears to have improved, it remains below an adequate level for much of the adult population of Victoria. Adequate monitoring is fundamental to assess whether the mandatory use of iodised salt in bread is effective in reducing iodine deficiency across all population groups. PMID- 21973247 TI - Mortality trends in Fiji. AB - OBJECTIVES: Mortality level and cause of death trends are evaluated to chart the epidemiological transition in Fiji. IMPLICATIONS for current health policy are discussed. METHODS: Published data for infant mortality rate (IMR), life expectancy (LE) and causes of death for 1940-2008 were assessed for quality, and compared with mortality indices generated from recent Ministry of Health death recording. Trends in credible mortality estimates are compared with trends in proportional mortality for cause of death. RESULTS: IMR declined from 60 deaths (per 1,000) in 1945 to below 20 by 2000. IMR for 2006-08 is estimated at 18-20 deaths per 1,000 live births. Excessive LE estimates arise by imputing from the IMR using inappropriate models. LE increased, but has been stable at 64 years for males and 69 years for females since the late 1980s and early 1990s respectively. Proportional mortality from diseases of the circulatory system has increased from around 20% in the 1960s to more than 45%. Extensive variation in published mortality estimates was indentified, including clearly incompatible ranges of IMR and LE. CONCLUSIONS: Mortality decline has stagnated. Relatively low IMR and proportional mortality trends suggest this is largely due to chronic diseases (especially cardiovascular) in adults. IMPLICATIONS: Reconciliation of mortality data in Fiji to reduce uncertainty is urgently needed. Fiji's health services and donor partners should place continued and increased emphasis on effective control strategies for cardiovascular disease. PMID- 21973248 TI - Higher HCV antibody prevalence among Indigenous clients of needle and syringe programs. AB - OBJECTIVE: To compare prevalence of hepatitis C virus (HCV) antibody and associated risk behaviours among Indigenous and non-Indigenous participants in the Australian Needle and Syringe Program Survey. METHODS: During 1 or 2 weeks each October from 1998 to 2008, clients of participating needle and syringe programs (NSPs) completed a self-administered questionnaire on demographics and risk behaviour and provided a capillary blood sample for HIV and HCV antibody testing. After de-duplication, 16,132 individuals participated during the 11 years, of whom 1,380 (8.6%) identified as Indigenous. RESULTS: Higher proportions of Indigenous than non-Indigenous participants were HCV antibody positive (57% versus 51%, p<0.001). In an overall multivariable analysis, Indigenous status (OR 1.17; CI 1.03-1.32) and female gender (OR 1.25; CI 1.16-1.35) were independently associated with HCV antibody seropositivity. Indigenous participants also reported higher rates of risk behaviour, including receptive sharing of needle syringes (21% vs 16%; p<0.001), receptive sharing of ancillary injecting equipment (38% vs 33%; p<0.001), having been injected by others (18% vs 13%; p<0.001), and injecting in public (54% vs 49%; p<0.001). CONCLUSION AND IMPLICATIONS: These results highlight the need for targeted, culturally appropriate programs to minimise risks for bloodborne viral transmission among Indigenous people who inject drugs. PMID- 21973249 TI - Kava drinking associated with suicidal behaviour among young Kanaks using kava in New Caledonia. AB - OBJECTIVE: To examine associations between recreational use of kava and indicators of suicidal behaviour among youth in New Caledonia. METHODS: This cross-sectional community-based survey was administered to 1,400 young people aged 16-25 years. A multivariate analysis tested for associations between lifetime kava use and lifetime suicidal ideation and attempts. Because ethnicity affected the correlation between kava use and suicidal behaviour, data were analysed separately for Kanak youth and youth of other ethnic communities. RESULTS: Overall, 42% of respondents reported any lifetime kava use, 34% reported past suicidal ideation and 12% any suicide attempts. Among Kanak youth, kava use increased the likelihood of reporting both suicidal ideation (aOR = 2.40, 95% CI: 1.58-3.66) and suicide attempts (aOR = 1.98, 95% CI: 1.11-3.52). No such association was found in the non-Kanak group. CONCLUSIONS: The discrepancy between the effects of kava drinking on suicidal behaviour between Kanak youth and youth of other ethnic groups may be related to differences in patterns and quantity of kava use. In view of the paucity of data on the effects of kava on mental health in young people, further investigation is required. IMPLICATIONS: The results call for an increased awareness of the potential adverse health effects of kava consumption in New Caledonia where it has spread in recent times and among communities where previously it was never used. PMID- 21973250 TI - Immigrant status and acculturation influence substance use among New Zealand youth. AB - OBJECTIVE: To investigate the associations between generational status, acculturation and substance use among immigrant and non-immigrant secondary school students in New Zealand. METHODS: A nationally representative sample of secondary school students in New Zealand was selected using a two-stage cluster sample design. Of the 8,999 students in the sample, 23.81% were first-generation immigrants and 20.90% were second-generation immigrants; the remaining 55.29% students are collectively referred to as 'non-immigrant' peers. Logistic regression models adjusted the associations of interest for age, gender, ethnicity, socioeconomic status and experience of ethnic discrimination. RESULTS: First and second-generation immigrants showed significantly lower risks of smoking cigarettes compared with their non-immigrant peers. Similar trends were apparent for consuming alcohol and marijuana weekly. The inclusion of some characteristics suggestive of acculturation in multivariable models did not influence the relationship between generational status and smoking cigarettes, but attenuated the apparent protective effect of being a first-generation immigrant with regard to alcohol and marijuana use. CONCLUSIONS AND IMPLICATIONS: The study shows the lower likelihood of substance use among newer immigrants in a nationally representative sample of New Zealand youth. Policies and health programs that build on this positive profile and reduce the risk of adverse changes over time require attention. PMID- 21973251 TI - Estimating the impact of mandatory folic acid fortification on the folic acid intake of Australian women of childbearing age. AB - OBJECTIVE: The primary aim of this study was to estimate the impact of mandatory folic acid (FA) fortification of bread-making flour on the FA intake of Australian women of childbearing age (16-44 years). The secondary objective was to investigate the relationship between estimated FA intake and socio-economic status (SES) and age. METHOD: Dietary modelling was used to estimate FA intake under four mandatory fortification scenarios--no supplement use, supplement use unrelated to FA intake, supplement use only among the highest consumers of bread, and increased supplement use. Data were obtained from the 1995 National Nutrition Survey for food intake patterns, the 2007 Victorian Population Health Survey for FA supplement use, and a marketplace survey. RESULTS: It is estimated that the National Health and Medical Research Council (NHMRC) recommendation for an additional 400 MUg/day [DOSAGE ERROR CORRECTED] FA will be achieved by a minimum of 3.9, 25.4, 21.7 and 30% of the target population under scenarios 1-4, respectively. The FA upper level of intake is exceeded by a maximum of 0.1, 1.7, 6.1 and 4.1% of the target population for scenarios 1-4, respectively. Conclusions : Mandatory FA fortification is not sufficient for the NHMRC recommendations for minimum and maximum intakes to be met by all of the target population under a number of plausible behaviour scenarios. IMPLICATIONS: Targeted nutrition education campaigns are needed for SES and age sub-groups and research of this nature should be extended to other population groups. Monitoring and evaluation of this policy will be important to ensure appropriate FA intake. PMID- 21973252 TI - Traffic emissions are associated with reduced fetal growth in areas of Perth, Western Australia: an application of the AusRoads dispersion model. AB - BACKGROUND: This study, in a region with relatively low industrial activity, used a highly specific marker for traffic emissions, accounted for the inherent fetal growth potential, and used complete record linkage of births, midwife notifications, deaths, hospital morbidity and birth defect records. METHODS: Clinical records were obtained for pregnancies between 2000 and 2006 in three areas of Perth, Western Australia (n=3,501). We used carbon monoxide as a marker for locally derived traffic emissions, and assessed exposure using the AusRoads dispersion model. Fetal growth was characterised by proportion of optimal birth weight and investigated using multivariate mixed-effects regression. RESULTS: Exposure in the third trimester was associated with a -0.49% (sd=0.23%) change in proportion of optimal birth weight per 10 MUg/m(3) increase in locally derived traffic emissions. However, this result was confined to one of the three study areas due to elevated exposure misclassification among women in the other two areas. Among this group, a neonate who would have otherwise attained an optimal birth weight of 3.5 kg would be expected to be born 58 g lighter for an interquartile increase in third trimester exposure, which was approximately half of the effect observed for maternal smoking during pregnancy. CONCLUSION: We observed an association between maternal exposure to traffic emissions and reduced fetal growth. This effect was supported by sensitivity analyses but only observed in one of the three study areas. Further studies are required to corroborate our results. PMID- 21973253 TI - Not a surgical vaccine: there is no case for boosting infant male circumcision to combat heterosexual transmission of HIV in Australia. AB - OBJECTIVE: To conduct a critical review of recent proposals that widespread circumcision of male infants be introduced in Australia as a means of combating heterosexually transmitted HIV infection. APPROACH: These arguments are evaluated in terms of their logic, coherence and fidelity to the principles of evidence based medicine; the extent to which they take account of the evidence for circumcision having a protective effect against HIV and the practicality of circumcision as an HIV control strategy; the extent of its applicability to the specifics of Australia's HIV epidemic; the benefits, harms and risks of circumcision; and the associated human rights, bioethical and legal issues. CONCLUSION: Our conclusion is that such proposals ignore doubts about the robustness of the evidence from the African random-controlled trials as to the protective effect of circumcision and the practical value of circumcision as a means of HIV control; misrepresent the nature of Australia's HIV epidemic and exaggerate the relevance of the African random-controlled trials findings to it; underestimate the risks and harm of circumcision; and ignore questions of medical ethics and human rights. The notion of circumcision as a 'surgical vaccine' is criticised as polemical and unscientific. IMPLICATIONS: Circumcision of infants or other minors has no place among HIV control measures in the Australian and New Zealand context; proposals such as these should be rejected. PMID- 21973254 TI - Accuracy of national mortality codes in identifying adjudicated cardiovascular deaths. AB - OBJECTIVE: This study investigated the sensitivity and specificity of the national mortality codes in identifying cardiovascular disease (CVD) deaths and documents methods of verification. METHODS: A 12-year retrospective case ascertainment of all ICD-coded CVD deaths was performed for deaths between 1990 and 2002 in the Melbourne Collaborative Cohort Study, comprising 41,528 subjects. Categories of non-CVD codes were also examined. Stratified samples of 750 deaths were adjudicated from a total of 2,230 deaths. Expert panels of cardiologists and neurologists adjudicated deaths. RESULTS: Of the 750 deaths adjudicated, 582 were verified as CVD [392 coronary heart disease (CHD) and 92 stroke] and 168 non-CVD. Estimated sensitivity and specificity of national mortality codes for identifying specific causes of death were: CHD 74.2% (95% CI: 69.8-78.5%) and 97.6% (96.0 99.2%), respectively; myocardial infarction 59.9% (50.9-69.0%) and 94.2% (92.4 96.0%), respectively; haemorrhagic stroke 58.9% (46.0-71.7%) and 99.8% (99.4 100.0%), respectively and; ischaemic stroke 38.7% (20.5-56.9%) and 99.9% (99.6 100.0%), respectively. Misclassification was most common for deaths with primary ICD codes for endocrine-metabolic and genito-urinary diseases. CONCLUSIONS: National mortality coding under-estimated the true proportion of CHD and stroke deaths in the cohort by 13.6% and 50.8%, respectively. IMPLICATIONS: Misclassification of cause of death may have implications for conclusions drawn from epidemiological research. PMID- 21973255 TI - Estimating cancer incidence in Indigenous Australians. AB - OBJECTIVE: To assess data quality of cancer registrations for Indigenous Australians and produce reliable national Indigenous cancer incidence statistics. METHODS: Completeness of Indigenous identification was assessed for the eight Australian cancer registries using an innovative indirect assessment method based on registry-specific registration rates for smoking-related cancers. National age standardised incidence rates and rate ratios (Indigenous:non-Indigenous) were calculated for all cancers combined and 26 individual cancer sites. Multivariate regression analysis was used to investigate trends in Indigenous cancer incidence by time or remoteness of residence, and whether the incidence rate ratio (Indigenous:non-Indigenous) was different in younger than older age-groups. RESULTS: Four registries covering 84% of the Indigenous population had sufficiently complete Indigenous identification to be included in analysis. Compared to other Australians, Indigenous Australians had much higher incidence of lung and other smoking-related cancers, cervix, uterus and liver cancer, but much lower incidence of breast, prostate, testis, colorectal and brain cancer, melanoma of skin, lymphoma and leukaemia. Incidence was higher in remote areas for some cancers (including several smoking-related cancers) but lower for others. The incidence rate ratios (IRRs) for smoking-related cancers were higher in younger than older people. CONCLUSIONS: Indigenous Australians have a different pattern of incidence of specific cancers than other Australians and large geographical variations for several cancers. IMPLICATIONS: All cancer registries need to further improve Indigenous identification, but national Indigenous cancer incidence statistics can, and should, be regularly reported. Tobacco control is a critical cancer-control issue for Indigenous Australians. PMID- 21973256 TI - Development and validation of reporting guidelines for studies involving data linkage. AB - OBJECTIVE: Data or record linkage is commonly used to combine existing data sets for the purpose of creating more comprehensive information to conduct research. Linked data may create additional concerns about error if cases are not linked accurately. It is important that factors compromising the quality of studies using linked data be reported in a clear and consistent way that allows readers and researchers to accurately appraise the results. The aim of this study was to develop and test reporting guidelines for evaluating the methodological quality of studies using linked data. METHOD: The development process included a literature review, a Delphi process and a validation process. Participants in the process were all Australian and included biostatisticians, epidemiologists, registry administrators, academic clinicians and a peer-reviewed journal editor. RESULTS: The final guidelines included four domains and 14 reporting items. These included: data sources (six items), research selected variables (four items), linkage technology and data analysis (three items), and ethics, privacy and data security (one item). CONCLUSION: This study is the first to develop guidelines for appraising the quality of reported data linkage studies. IMPLICATIONS: These guidelines will assist authors to report their results in a consistent, high quality manner. They will also assist readers to interpret the quality of results derived from data linkage studies. PMID- 21973257 TI - Telephone survey methods: implications of the increasing mobile-only population for public health research. PMID- 21973258 TI - Can health partnerships re-orientate health care toward prevention? PMID- 21973259 TI - Fish oil supplementation, learning and behaviour in Indigenous Australian children from a remote community school: a pilot feasibility study. PMID- 21973260 TI - Developing a health workforce from an underserved population in New Zealand. PMID- 21973261 TI - Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine. AB - OBJECTIVE: An observational safety study of the quadrivalent human papillomavirus vaccine (HPV4) in women was conducted. This report presents findings from autoimmune surveillance. Design. Subjects were followed for 180days after each HPV4 dose for new diagnoses of 16 prespecified autoimmune conditions. SETTING: Two managed care organizations in California. Subjects. Number of 189,629 women who received >=1 dose of HPV4 between 08/2006 and 03/2008. OUTCOME: Potential new onset autoimmune condition cases amongst HPV4 recipients were identified by electronic medical records. Medical records of those with >=12-month health plan membership prior to vaccination were reviewed by clinicians to confirm the diagnosis and determine the date of disease onset. The incidence of each autoimmune condition was estimated for unvaccinated women at one study site using multiple imputations and compared with that observed in vaccinated women. Incidence rate ratios (IRR) were calculated. Findings were reviewed by an independent Safety Review Committee (SRC). RESULTS: Overall, 1014 potential new onset cases were electronically identified; 719 were eligible for case review; 31 40% were confirmed as new onset. Of these, no cluster of disease onset in relation to vaccination timing, dose sequence or age was found for any autoimmune condition. None of the estimated IRR was significantly elevated except Hashimoto's disease [IRR=1.29, 95% confidence interval: 1.08-1.56]. Further investigation of temporal relationship and biological plausibility revealed no consistent evidence for a safety signal for autoimmune thyroid conditions. The SRC and the investigators identified no autoimmune safety concerns in this study. CONCLUSIONS: No autoimmune safety signal was found in women vaccinated with HPV4. PMID- 21973262 TI - Physical connection decreases benefits of clonal integration in Alternanthera philoxeroides under three warming scenarios. AB - Physical connection between ramets usually allows clonal plants to perform better but can have the opposite effects in some cases. Clonal integration and the effects of climate warming have been extensively studied, but to date little is known about how climate warming affects the benefits of clonal integration. We conducted a field experiment in which Alternanthera philoxeroides segments with connected and severed stolons were subject to four climate regimes (ambient, day warming, night warming and daily warming), and measured final biomass, number of ramets and total length of stolons. Across the three warming treatments, temperature rise suppressed growth of clonal fragments with connected stolons but increased growth of fragments with severed stolons; temperature rise affected the biomass of distal ramets but not proximal ramets, and had similar effects on the numbers of proximal and distal ramets. When the three warming treatments were considered separately, they had contrasting consequences for the benefits of clonal integration. Specifically, when fragments were exposed to day and night warming, physical connection evened out the advantages of clonal integration that occur under ambient conditions; when fragments were exposed to daily warming, physical connection led to smaller clonal plants. These findings suggest that physical connection between ramets may be disadvantageous to overall performance of A. philoxeroides fragments under climate warming, and also indicate that the net consequences of daily warming outweigh those of day or night warming. PMID- 21973263 TI - Handling of radical prostatectomy specimens: total or partial embedding? PMID- 21973264 TI - Patterns of muscle activation during generalized tonic and tonic-clonic epileptic seizures. AB - PURPOSE: Tonic seizures and the tonic phase of tonic-clonic epileptic seizures are defined as "sustained tonic" muscle contraction lasting a few seconds to minutes. Visual inspection of the surface electromyogram (EMG) during seizures contributed considerably to a better understanding and accurate diagnosis of several seizure types. However, quantitative analysis of the surface EMG during the epileptic seizures has received surprisingly little attention until now. The aim of our study was to elucidate the pathomechanism of the tonic muscle activation during epileptic seizures. METHODS: Surface EMG was recorded from the deltoid muscles, on both sides, during 63 seizures from 20 patients with epilepsy (10 with generalized tonic and 10 with tonic-clonic seizures). Twenty age- and gender-matched normal controls simulated 100 generalized tonic seizures. To characterize the signal properties we calculated the root mean square (RMS) of the amplitudes, the median frequency (MF), and the coherence. Based on the spectrograms of both epileptic and simulated seizures, we chose to determine the relative spectral power (RP) in the higher (100-500 Hz) frequency domain. KEY FINDINGS: During the tonic seizures there was a significant shift toward higher frequencies, expressed by an increase in the MF and the RP (100-500 Hz). The amplitude characteristic of the signal (RMS) was significantly higher during the tonic phase of the tonic-clonic seizures as compared to the simulated ones, whereas the RMS of the tonic seizures was significantly lower than the simulated ones. The EMG-EMG coherence was significantly higher during the epileptic seizures (both types) as compared to the simulated ones. SIGNIFICANCE: Our results indicate that the mechanism of muscle activation during epileptic seizures is different from the physiologic one. Furthermore the sustained muscle activation during the tonic phase of tonic-clonic seizures is different from that during tonic seizures: The tonic phase of tonic-clonic seizures is characterized by increased amplitude of the signal, whereas tonic seizures are produced by a significant increase in the frequency of the signal. PMID- 21973265 TI - Recombinant amphiphilic protein micelles for drug delivery. AB - Amphiphilic block polypeptides can self-assemble into a range of nanostructures in solution, including micelles and vesicles. Our group has recently described the capacity of recombinant amphiphilic diblock copolypeptides to form highly stable micelles. In this report, we demonstrate the utility of protein nanoparticles to serve as a vehicle for controlled drug delivery. Drug-loaded micelles were produced by encapsulating dipyridamole as a model hydrophobic drug with anti-inflammatory activity. Murine studies confirmed the capacity of drug loaded protein micelles to limit the in vivo recruitment of neutrophils in response to an inflammatory stimulus. PMID- 21973266 TI - Malus hupehensis NPR1 induces pathogenesis-related protein gene expression in transgenic tobacco. AB - Most commercially grown apple cultivars are susceptible to fungal diseases. Malus hupehensis has high resistance to many diseases affecting apple cultivars. Understanding innate defence mechanisms would help to develop disease-resistant apple crops. Non-expressor of pathogenesis-related genes 1 (NPR1) plays a key role in regulating salicylic acid (SA)-mediated systemic acquired resistance (SAR). MhNPR1 cDNA, corresponding to genomic DNA and its 5' flanking sequences, was isolated from M. hupehensis. Sequence analysis showed that the regulatory mechanism for oligomer-monomer transition of the MhNPR1 protein in apple might be similar to that of GmNPR1 in soybean, but different from that of AtNPR1 in Arabidopsis. No significant differences in MhNPR1 expression were found in M. hupehensis after infection with Botryosphaeria berengeriana, showing that MhNPR1 might be regulated by pathogens at the protein level, as described for Arabidopsis and grapevine. SA treatment significantly induced MhNPR1 expression in leaves, stems and roots, while methyl jasmonate (MeJA) treatment induced MhNPR1 expression in roots, but not in leaves or stems. The expression of MhNPR1 was highly increased in roots, moderately in leaves, and did not change in stems after treatment with 1-aminocyclopropane-1-carboxylic acid (ACC). SAR marker genes (MhPR1 and MhPR5) were induced by SA, MeJA and ACC in leaves, stems and roots. Overexpression of MhNPR1 significantly induced the expression of pathogenesis-related genes (NtPR1, NtPR3 and NtPR5) in transgenic tobacco plants and resistance to the fungus Botrytis cinerea, suggesting that MhNPR1 orthologues are a component of the SA defence signalling pathway and SAR is induced in M. hupehensis. PMID- 21973267 TI - Penetration of anti-infective agents into pulmonary epithelial lining fluid: focus on antifungal, antitubercular and miscellaneous anti-infective agents. AB - Epithelial lining fluid (ELF) is often considered to be the site of extracellular pulmonary infections. During the past 25 years, a limited number of studies have evaluated the intrapulmonary penetration of antifungal, antitubercular, antiparasitic and antiviral agents. For antifungal agents, differences in drug concentrations in ELF or bronchoalveolar lavage (BAL) fluid were observed among various formulations or routes of administration, and between agents within the same class. Aerosolized doses of deoxycholate amphotericin B, liposomal amphotericin B and amphotericin B lipid complex resulted in higher concentrations in ELF or BAL fluid than after intravenous administration. The mean concentrations in ELF following intravenous administration of both anidulafungin and micafungin ranged between 0.04 and 1.38 MUg/mL, and the ELF to plasma concentration ratios (based on the area under the concentration-time curve for total drug concentrations) were between 0.18 and 0.22 during the first 3 days of therapy. Among the azole agents, intravenous administration of voriconazole resulted in the highest mean ELF concentrations (range 10.1-48.3 MUg/mL) and ratio of penetration (7.1). The range of mean ELF concentrations of itraconazole and posaconazole following oral administration was 0.2-1.9 MUg/mL, and the ELF to plasma concentration ratios were <1. A series of studies have evaluated the intrapulmonary penetration of first- and second-line oral antitubercular agents in healthy adult subjects and patients with AIDS. The ELF to plasma concentration ratio was >1 for isoniazid, ethambutol, pyrazinamide and ethionamide. For rifampicin (rifampin) and rifapentine, the ELF to plasma concentration ratio ranged between 0.2 and 0.32, but in alveolar macrophages the concentration of rifampicin was much higher (145-738 MUg/mL compared with 3.3-7.5 MUg/mL in ELF). No intrapulmonary studies have been conducted for rifabutin. Sex, AIDS status or smoking history had no significant effects on the magnitude of ELF concentrations of antitubercular agents. Subjects who were slow acetylators had higher plasma and ELF concentrations of isoniazid than those who were fast acetylators. Penetration of dapsone into ELF was very good, with the range of mean ELF to plasma concentration ratios being 0.65-2.91 at individual sampling times over 48 hours. Once-daily dosing of aerosolized pentamidine resulted in higher concentrations in BAL fluid than after intravenous administration. The mean BAL concentrations at 15-32 days after once- or twice-monthly administration of aerosolized pentamidine 300 and 600 mg ranged from 6.5 to 28.4 ng/mL. No differences in pentamidine BAL concentrations were observed in symptomatic patients who developed Pneumocystis jirovecii pneumonia compared with patients who did not. Zanamivir concentrations in ELF were similar in magnitude (range 141 326 ng/mL) following administration by continuous intravenous infusion (3 mg/hour), oral inhalation (10 mg every 12 hours) and intravenous bolus (200 mg every 12 hours). Data from case reports have suggested that concentrations of nelfinavir and saquinavir in ELF are undetectable, whereas tipranavir and lopinavir had measureable ELF concentrations (2.20 MUmol/L and 14.4 MUg/mL, respectively) when these protease inhibitors were co-administrated with ritonavir. While the clinical significance of ELF or BAL concentrations remains unknown for this group of anti-infective agents, the knowledge of drug penetration into the extracellular space of the lung should assist in re evaluating and designing specific dosing regimens for use against potential pathogens. PMID- 21973269 TI - Effect of pH and comedication on gastrointestinal absorption of posaconazole: monitoring of intraluminal and plasma drug concentrations. AB - BACKGROUND AND OBJECTIVE: Posaconazole (Noxafil(r)) is an extended-spectrum triazole antifungal agent for prevention and treatment of invasive fungal infections. An inadequate dietary intake and abnormal gastric pH levels are common in critically ill patients receiving antifungal treatment with posaconazole, resulting in unpredictable bioavailability and sub-therapeutic plasma concentrations. This study was carried out to elucidate the impact of pH on posaconazole absorption and to explore the underlying mechanisms of enhanced intestinal absorption when coadministering an acidic carbonated beverage. In contrast to previously published studies, in which only plasma concentrations were determined, we also explored the gastric and intestinal behaviour of posaconazole after a single oral dose. METHODS: A crossover study was performed in five healthy subjects. A single dose (10 mL) of posaconazole suspension (40 mg/mL) was administered orally in four different conditions: with 330 mL of water (condition 1); with 330 mL of a cola beverage [Coca-Cola(r)] (condition 2); with 330 mL of water following intake of the proton pump inhibitor esomeprazole 40 mg once daily for 3 days (condition 3); or with 330 mL of Coca-Cola(r) following intake of esomeprazole 40 mg once daily for 3 days (condition 4). After administration, gastrointestinal fluid and plasma samples were collected at regular time points, and posaconazole concentrations were determined. RESULTS: Compared with administration with water, coadministration of Coca-Cola(r) did not alter the pH of the intraluminal environment but did significantly increase posaconazole gastric concentrations (+102%; p < 0.001) and systemic exposure (+70%; p < 0.05). This enhancement could be attributed to improved posaconazole solubility in Coca-Cola(r) and prolonged gastric residence. Coadministration of esomeprazole led to an increased gastric pH, which was accompanied by decreased posaconazole absorption; the mean plasma and gastric area under the concentration time curve (AUC) values decreased by 37% and 84%, respectively. Simultaneous intake of Coca-Cola(r) could not completely compensate for the increase in pH induced by esomeprazole; compared with the reference condition, the mean plasma and gastric AUC values were still decreased by 19% and 73%, respectively. A good correlation between plasma and gastric posaconazole concentrations was observed (r = 0.8165; p < 0.0001), indicating that dissolution in the stomach dictates absorption of posaconazole. CONCLUSIONS: These results demonstrate that coadministration of Coca-Cola(r) has a positive effect on posaconazole bioavailability in the fasted state. However, it can only be considered a partially efficient strategy to increase absorption in patients with inadequate food intake who exhibit abnormal gastric pH levels due to coadministration of acid-suppressive agents. PMID- 21973270 TI - Pharmacokinetics of metformin in girls aged 9 years. AB - BACKGROUND AND OBJECTIVE: Metformin is a biguanide used in the treatment of type 2 diabetes mellitus. In girls with a low birth weight, and early-normal and rapidly progressive puberty, metformin therapy is capable of modifying this outcome, prolonging pubertal growth, increasing height gain, delaying the age at menarche towards normal and improving the endocrine-metabolic status of these girls. The pharmacokinetics of metformin have been studied in healthy adults and in patients with type 2 diabetes. The objective of this study was to study the pharmacokinetics of metformin in young, non-obese girls. METHODS: The study population consisted of six girls with a combined history of low birth weight and early-normal onset of puberty. At the time of the study, these girls were aged 9 years and had been receiving metformin (850 mg/day at dinner time) for a mean duration of 8 months. Blood samples were obtained from the girls before metformin intake and for 12 hours thereafter. Serum metformin concentrations were assessed by liquid chromatography with tandem mass spectrometry. The area under the serum concentration-time curve (AUC), maximum serum concentration (C(max)), time to reach the C(max) (t(max)), half-life (t(½)), volume of distribution (V(d)) and total clearance (CL) were calculated. RESULTS: Metformin concentration-time curves were similar in girls receiving similar metformin doses (range 21-29 mg/kg): in those girls, the mean AUC was 21 mg . h/L, with a C(max) of 3 mg/L, t(max) of 2.5 hours, t(½) of 4 hours, V(d) of 111 L and CL of 20 L/h. These values are comparable to those observed in adults. CONCLUSION: In girls aged 9 years, the pharmacokinetics of metformin were comparable to those in adults. Trial registration number (International Standard Randomized Controlled Trial Number Register): ISRCTN49334271. PMID- 21973268 TI - Pharmacokinetics of antimalarials in pregnancy: a systematic review. AB - Malaria is a serious parasitic infection, which affects millions of people worldwide. As pregnancy has been shown to alter the pharmacokinetics of many medications, the efficacy and safety of antimalarial drug regimens may be compromised in pregnant women. The objective of this review is to systematically review published literature on the pharmacokinetics of antimalarial agents in pregnant women. A search of MEDLINE (1948-May 2011), EMBASE (1980-May 2011), International Pharmaceutical Abstracts (1970-May 2011), Google and Google Scholar was conducted for articles describing the pharmacokinetics of antimalarials in pregnancy (and supplemented by a bibliographic review of all relevant articles); all identified studies were summarized and evaluated according to the level of evidence, based on the classification system developed by the US Preventive Services Task Force. Identified articles were included in the review if the study had at least one group that reported at least one pharmacokinetic parameter of interest in pregnant women. Articles were excluded from the review if no pharmacokinetic information was reported or if both pregnant and non-pregnant women were analysed within the same group. For quinine and its metabolites, there were three articles (one level II-1 and two level III); for artemisinin compounds, two articles (both level III); for lumefantrine, two articles (both level III); for atovaquone, two articles (both level III); for proguanil, three articles (one level II-1 and two level III); for sulfadoxine, three articles (all level II-1); for pyrimethamine, three articles (all level II-1); for chloroquine and its metabolite, four articles (three level II-1 and one level II-3); for mefloquine, two articles (one level II-1 and one level III); and for azithromycin, two articles (one level II-1 and one level III). Although comparative trials were identified, most of these studies were descriptive and classified as level III evidence. The main findings showed that pharmacokinetic parameters are commonly altered in pregnancy for the majority of recommended agents. Importantly, first-line regimens of artemisinin-based compounds, lumefantrine, chloroquine and pyrimethamine/sulfadoxine may undergo significant changes that could decrease therapeutic efficacy. These changes are usually due to increases in the apparent oral clearance and volume of distribution that commonly occur in pregnant women, and may result in decreased exposure and increased therapeutic failure. In order to assess the clinical implications of these changes and to provide safe and effective dosage regimens, there is an immediate need for dose-optimization studies of all recommended first- and second line agents used in pregnant women with malaria. PMID- 21973272 TI - Obesity and allometric scaling of pharmacokinetics. PMID- 21973271 TI - Population pharmacokinetics and pharmacodynamics of propofol in morbidly obese patients. AB - BACKGROUND AND OBJECTIVES: In view of the increasing prevalence of morbidly obese patients, the influence of excessive total bodyweight (TBW) on the pharmacokinetics and pharmacodynamics of propofol was characterized in this study using bispectral index (BIS) values as a pharmacodynamic endpoint. METHODS: A population pharmacokinetic and pharmacodynamic model was developed with the nonlinear mixed-effects modelling software NONMEM VI, on the basis of 491 blood samples from 20 morbidly obese patients (TBW range 98-167 kg) and 725 blood samples from 44 lean patients (TBW range 55-98 kg) from previously published studies. In addition, 2246 BIS values from the 20 morbidly obese patients were available for pharmacodynamic analysis. RESULTS: In a three-compartment pharmacokinetic model, TBW proved to be the most predictive covariate for clearance from the central compartment (CL) in the 20 morbidly obese patients (CL 2.33 L/min * [TBW/70]^[0.72]). Similar results were obtained when the morbidly obese patients and the 44 lean patients were analysed together (CL 2.22 L/min * [TBW/70]^[0.67]). No covariates were identified for other pharmacokinetic parameters. The depth of anaesthesia in the morbidly obese patients was adequately described by a two-compartment biophase-distribution model with a sigmoid maximum possible effect (E(max)) pharmacodynamic model (concentration at half-maximum effect [EC(50)] 2.12 mg/L) without covariates. CONCLUSION: We developed a pharmacokinetic and pharmacodynamic model of propofol in morbidly obese patients, in which TBW proved to be the major determinant of clearance, using an allometric function with an exponent of 0.72. For the other pharmacokinetic and pharmacodynamic parameters, no covariates could be identified. Trial registration number (clinicaltrials.gov): NCT00395681. PMID- 21973274 TI - Molecular cloning of a copper-dependent laccase from the dye-decolorizing strain Stenotrophomonas maltophilia AAP56. AB - AIMS: To clone the gene encoding the enzyme with laccase activity expressed by Stenotrophomonas maltophilia AAP56 and to construct an insertional mutation in that gene to determine its effect on dye decolourization and laccase activity in this strain. METHODS AND RESULTS: Comparative genomics of Sten. maltophilia strains K279a and R551-3 revealed copA (coding for putative multicopper oxidase) as a candidate gene to encode an enzyme with laccase activity. Stenotrophomonas maltophilia AAP56 copA was amplified by degenerated PCR and cloned. A copA mutant strain, named Stemur, was constructed by homologous recombination. The comparison of wild-type and mutant strains revealed that CopA shows laccase activity, and it is involved in copper resistance and in vitro dye decolorization. On the contrary, the mutation in copA did not affect the in vivo dye removal by Sten. maltophilia. CONCLUSIONS: Stenotrophomonas maltophilia AAP56 shows different mechanisms for dye decolorization. The gene encoding the laccase has been identified, and it has been shown that it is involved in the in vitro decolorization. SIGNIFICANCE AND IMPACT OF THE STUDY: Stenotrophomonas maltophilia is a micro-organism of interest in different biotechnological processes including dye removal. This is the first report to address the molecular mechanism of this capacity, what will contribute to further improvements in the process. PMID- 21973275 TI - Stabilization and study of SrFe(1-x)Mn(x)O2 oxides with infinite-layer structure. AB - A series of layered oxides of nominal composition SrFe(1-x)Mn(x)O(2) (x = 0, 0.1, 0.2, 0.3) have been prepared by the reduction of three-dimensional perovskites SrFe(1-x)Mn(x)O(3-delta) with CaH(2) under mild temperature conditions of 583 K for 2 days. The samples with x = 0, 0.1, and 0.2 exhibit an infinite-layer crystal structure where all of the apical O atoms have been selectively removed upon reduction. A selected sample (x = 0.2) has been studied by neutron powder diffraction (NPD) and X-ray absorption spectroscopy. Both techniques indicate that Fe and Mn adopt a divalent oxidation state, although Fe(2+) ions are under tensile stress whereas Mn(2+) ions undergo compressive stress in the structure. The unit-cell parameters progressively evolve from a = 3.9932(4) A and c = 3.4790(4) A for x = 0 to a = 4.00861(15) A and c = 3.46769(16) A for x = 0.2; the cell volume presents an expansion across the series from V = 55.47(1) to 55.722(4) A(3) for x = 0 and 0.2, respectively, because of the larger effective ionic radius of Mn(2+) versus Fe(2+) in four-fold coordination. Attempts to prepare Mn-rich compositions beyond x = 0.2 were unsuccessful. For SrFe(0.8)Mn(0.2)O(2), the magnetic properties indicate a strong magnetic coupling between Fe(2+) and Mn(2+) magnetic moments, with an antiferromagnetic temperature T(N) above room temperature, between 453 and 523 K, according to temperature dependent NPD data. The NPD data include Bragg reflections of magnetic origin, accounted for with a propagation vector k = ((1)/(2), (1)/(2), (1)/(2)). A G-type antiferromagnetic structure was modeled with magnetic moments at the Fe/Mn position. The refined ordered magnetic moment at this position is 1.71(3) MU(B)/f.u. at 295 K. This is an extraordinary example where Mn(2+) and Fe(2+) ions are stabilized in a square-planar oxygen coordination within an infinite layer structure. The layered SrFe(1-x)Mn(x)O(2) oxides are kinetically stable at room temperature, but in air at ~170 degrees C, they reoxidize and form the perovskites SrFe(1-x)Mn(x)O(3-delta). A cubic phase is obtained upon reoxidation of the layered compound, whereas the starting precursor SrFeO(2.875) (Sr(8)Fe(8)O(23)) was a tetragonal superstructure of perovskite. PMID- 21973276 TI - How often do patients return to the operating room after colorectal resections? AB - AIM: We sought to identify the rate of re-operation after an index colorectal surgical procedure and potential contributing risk factors. METHOD: This is a retrospective cohort study from the American College of Surgeons National Surgical Quality Improvement Program. We identified all patients who either returned or did not return to the operating room after any colorectal resection from January 2005 to December 2008. RESULTS: From a total cohort of 635, 265 patients included in the National Surgical Quality Improvement Program over the 4 year study period, we identified 54, 237 patients who underwent colorectal operations. A return to the operating room was coded in 5.4 +/- 0.1% of non colorectal resection patients and 7.6 +/- 0.2% of colorectal resection patients (P < 0.001). The multivariate model identified patients with postoperative diagnostic codes for abdominal cavity hernia or colostomy complication as having the highest odds of return to the operating room within 30 days. Patients returning to the operating room had longer length of stay and higher overall mortality compared with those patients who did not return to the operating room. CONCLUSION: Return to the operating room is a relatively common occurrence after colorectal resections, with an associated high rate of mortality. Given the association between return to the operating room and adverse patient outcomes, emphasis should be placed on determining strategies to reduce the need for return to the operating room. PMID- 21973277 TI - Self-reported symptoms in patients on antiepileptic drugs in monotherapy. AB - OBJECTIVE: To ascertain the frequency of self-reported symptoms in patients taking antiepileptic drugs (AED). METHODS: We included patients on carbamazepine (CBZ) n = 36, valproate (VPA) n = 21, levetiracetam (LEV) n = 12, phenytoin (PHT) n = 11, lamotrigine (LTG) n = 20, patients not taking anticonvulsive drugs n = 19, and healthy control subjects (CTRL) n = 41 to complete the Liverpool Adverse Event Profile (LAEP). RESULTS: The mean LAEP scores were CBZ/PHT/LEV/VPA/LTG/noAED/CTRL = 44.97/42.00/41.00/40.33/32.42/42.00/30.80. LEV scored overall in the same range as the older AED but had a different adverse effect profile with self-reported anger (33%) and shaky hands (42%) particularly frequent. Patients with depression or uncontrolled epilepsy had significantly higher LAEP scores than patients without depression or uncontrolled epilepsy. CONCLUSION: Our unblinded observational study of self-reported symptoms suggested LTG was overall the drug with the least self-reported symptoms. Larger studies are needed to determine whether this was a truly significant difference. LEV had a different side effect profile to older AED. Confounding factors were depression and uncontrolled epilepsy. This observation should be further tested with randomized studies. PMID- 21973278 TI - Progesterone levels in amyotrophic lateral sclerosis. PMID- 21973280 TI - Characterisation and natural variation of a dehydrin gene in Quercus petraea (Matt.) Liebl. AB - For the first time in sessile oak [Quercus petraea (Matt.) Liebl.], the isolation and characterisation of a full-length dehydrin gene and its promoter region, as well as its allelic variation in natural populations, is reported. Dehydrins (Dhn) are stress-related genes important for the survival of perennial plants in a seasonal climate. A full-length dehydrin gene (Dhn3) was characterised at the nucleotide level and the protein structure was modelled. Additionally, the allelic variation was analysed in five natural populations of Quercus petraea (Matt.) Liebl. sampled along an altitudinal gradient in the French Pyrenees. The analysed sequences contain typical domains of the K(n) class of dehydrins in the coding region. Also, the 5'untranslated region (promoter) of the gene was amplified, which shows typical motifs essential for drought- and cold-responsive gene expression. Single nucleotide substitutions and indels (insertions/deletions) within the coding region determine large biochemical differences at the protein level. However, only low levels of genetic differentiation between populations from different altitudes were detectable. PMID- 21973281 TI - Effects of horizontal misfit and bar framework material on the stress distribution of an overdenture-retaining bar system: a 3D finite element analysis. AB - PURPOSE: To evaluate the influence of horizontal misfit change and bar framework material on the distribution of static stresses in an overdenture-retaining bar system using finite element (FE) analysis. MATERIALS AND METHODS: A 3D FE model was created including two titanium implants and a bar framework placed in the anterior part of a severely resorbed jaw. The model set was exported to mechanical simulation software, where horizontal displacement (10, 50, 100, and 200 MUm) was applied simulating the settling of the framework, which suffered shrinkage during laboratory procedures. Four bar materials (gold alloy, silver palladium alloy, commercially pure titanium, and cobalt-chromium alloy) were also simulated in the analysis using 50 MUm as the horizontal misfit. Data were qualitatively evaluated using von Mises stress, given by the software. RESULTS: The misfit amplification presented a great increase in the stress levels in the inferior region of the bar, screw-retaining neck, cervical and medium third of the implant, and cortical bone tissue surrounding the implant. The higher stiffness of the bar presented a considerable increase in the stress levels in the bar framework only. CONCLUSION: The levels of static stresses seem to be closely linked with horizontal misfit, such that its amplification caused increased levels of stress in the structures of the overdenture-retaining bar system. On the other hand, the stiffness of the bar framework presented a lower effect on the static stress levels. PMID- 21973282 TI - Bridging the gap: addressing challenges toward improvement of cleft teamwork in a tertiary care center in north India: a pilot study. AB - Aim : The aim of this study was the initiation of systematic data collection so as to improve the capacity for outcome measurement after cleft repair. Also, a clinical audit was done for evaluation of the process and assessment of outcomes of cleft care. Design and Setting : A questionnaire-based survey and outcome assessment was carried out over a 1-year period from March 2008 to February 2009 at the combined outpatient cleft clinic of a tertiary care center in India. Patients and Participants : Data collection (basic demographic and environmental information) was done twice a week throughout the year by students from the Department of Pediatric Dentistry, at the outpatient cleft clinic. Results : A total of 68 completed cleft lip and palate registry forms, from which all the information was available, were analyzed. There was a skewed sex ratio, with a higher preponderance of boys seeking treatment. Of affected males, 19.1% were between 2 and 5 years of age when they first reported to the cleft clinic. Surprisingly, no bilateral clefts of lip, unilateral cleft lip (right) and unilateral cleft lip and palate (right) were observed in girls. Oral health was poor in 74% of patients; among the dental referrals only 26% could be recruited for orthodontics with a reasonably good prognosis. Conclusions : Poverty, illiteracy, and superstitions prevent an average patient from India from receiving multidisciplinary cleft care. This emphasizes the need to create systems that suit the needs of our target patients. PMID- 21973283 TI - AAOHN Lillian Carter humanitarian award. PMID- 21973284 TI - 2011 AAOHN Lillian Carter humanitarian award winner: Annette B. Haag, MA, RN, COHN-S/CM, FAAOHN. PMID- 21973285 TI - Protecting pregnant health care workers from occupational hazards. AB - The safety of pregnant health care workers and their infants is paramount. The scope and variety of hazards within the health care field is profound and diverse. The occupational health nurse can identify early risks and correct them, as well as provide ongoing surveillance, counseling, and prudent policy recommendations for the multitude of hazards to which pregnant health care workers are exposed. Policy must reflect the real risks taken by these workers every day they go to work, and how those risks will affect them, their immediate families, and future generations. PMID- 21973286 TI - Swedish entrepreneurs' use of occupational health services. AB - Small-scale enterprises are less often covered by occupational health services and have insufficient awareness about health and risks in the work environment. This study investigated how Swedish entrepreneurs in small-scale enterprises use occupational health services. The study used a questionnaire sent in two waves, 5 years apart. At baseline, 496 entrepreneurs responded, and 251 participated 5 years later. The questionnaire included items about affiliation with and use of occupational health services, physical and psychosocial work environments, work environment management, sources of work environment information, and membership in professional networks. Only 3% of entrepreneurs without employees and 19% of entrepreneurs with employees were affiliated with an occupational health service. Entrepreneurs affiliated with occupational health services were more active in work environment management and gathering information about the work environment. The occupational health services most used were health examinations, health care, and ergonomic risk assessments. Affiliation with occupational health services was 6% at both measurements, 4% at baseline, and 10% 5 years later. PMID- 21973287 TI - Focus on the aging worker. AB - This article discusses select characteristics of the aging work force, health related issues that can impact work productivity, and strategies and resources that can foster a more productive work environment. The older work force is vital to the future of the U.S. economy. Employers should recognize the value of older workers. Occupational health nurses can assist older workers in maintaining and optimizing their health. PMID- 21973289 TI - Eating disorders at work. AB - CDC statistics reflect the dramatic increase in obesity in the United States in the past 20 years, with 33 states having a prevalence of 25% or greater. Eating disorders and obesity have major implications for occupational health nurses. PMID- 21973290 TI - 60Co-gamma radiation induces differential acetylation and phosphorylation of histones H3 and H4 in wheat. AB - Histone modifications occur during DNA damage and repair in eukaryotes. These modifications were analysed in wheat seedlings exposed to (60) Co-gamma radiation. Seedling height was not significantly affected in the first 2 days after irradiation up to 150 Gy. Subsequently, in the next 2 weeks, there was 30 40% reduction in seedling height, indicating that there were late effects of irradiation. The histones isolated from irradiated seedlings were analysed in the initial stages for modifications of H3 and H4 using antibodies. Global acetylation of H3 decreased and H4 increased in a dose-dependent manner till 100 Gy. The time course of individual modifications showed that for H3K4 and H3K9, acetylation decreased, whereas for H3S10 phosphorylation increased. There were fluctuations in acetylation of H4K5, H4K12 and H4K16, whereas H4K8 showed hyper acetylation. The results indicate that gamma radiation induced DNA damage and repair in wheat seedlings and initiated differential acetylation of H3 and H4. This is the first report in plants on site-specific H3 and H4 modifications in response to exposure to ionizing radiation. PMID- 21973291 TI - Combination of 595-nm pulsed dye laser, long-pulsed 755-nm alexandrite laser and microdermabrasion treatment for keratosis pilaris. PMID- 21973292 TI - Smallpox: should we destroy the last stockpile? PMID- 21973293 TI - Why is cytomegalovirus the most frequent cause of congenital infection? PMID- 21973294 TI - Will we ever see the approval of a Staphylococcus aureus vaccine? PMID- 21973297 TI - Early viral kinetics: a novel guide for optimal dosing frequency of pegylated interferon-alpha-2a in HIV/HCV-coinfected patients. AB - The success rate in HCV treatment of HIV/HCV-coinfected patients is still unsatisfactory and new strategies are required to improve the effectiveness of current regimens and eventually optimize the oncoming new antiviral drugs. This article assesses the findings of a recently published paper comparing pharmacokinetics, pharmacodynamics and HCV decay with twice-weekly dosing of pegylated IFN-alpha-2a versus the standard weekly dosing, and weight-based ribavirin. A more rapid HCV-RNA decline was observed in the twice-weekly pegylated interferon arm and associated with a higher induction of interferon stimulated genes, despite a similar pharmacokynetic profile between the two dosing schedules. This promising novel therapeutic approach to improve sustained virologic response in difficult-to-treat populations is discussed in relation to the key findings of the article. PMID- 21973296 TI - Laninamivir octanoate: a new long-acting neuraminidase inhibitor for the treatment of influenza. AB - Oseltamivir and zanamivir are well-established and well-researched drugs for the treatment of influenza in Japan and the rest of the world. A new neuraminidase inhibitor, laninamivir octanoate, has been approved for use in Japanese clinics. Laninamivir octanoate is an inhaled drug with unique characteristics. The inhaled laninamivir octanoate is converted into its active form, laninamivir, in the lungs where a high concentration persists for a long period of time. The concentration of laninamivir exceeds the level necessary for influenza virus replication inhibition for at least 5 days, thus influenza can be treated with a single administration. The drug is delivered using one device requiring four inhalations for children and two devices requiring eight inhalations for adults. Clinical trials have shown comparable efficacy for laninamivir octanoate and oseltamivir. Laninamivir octanoate also displayed a sufficient antiviral effect to treat infection with H275Y-mutated oseltamivir-resistant virus. Laninamivir octanoate has displayed clinical efficacy comparable to that of oseltamivir and zanamivir against the H1N1 pandemic influenza strain from 2009, seasonal H3N2 influenza and influenza B viruses. The prophylactic efficacy of laninamivir octanoate has been shown in animal models. The effectiveness of laninamivir against the highly pathogenic avian influenza virus H5N1 has also been shown in vitro and in animal models. A major clinical benefit of this drug is that the single administration is very convenient for both the patient and doctor, which leads to improved compliance. Furthermore, this drug shows promise for the treatment of influenza in future pandemics. PMID- 21973298 TI - Improving diagnosis of urogenital schistosome infection. AB - Schistosomiasis (commonly known as bilharzia or snail fever) is the second (to malaria) most important human parasitic disease in tropical and subtropical in regions. In Africa, Schistosoma haematobium, the causative agent of urogenital schistosomiasis, is the most prevalent species causing human disease and is responsible for most of the schistosome-related disease in the region. Diagnosis of morbidity in field settings mainly relies on the detection of hematuria (blood in the urine) and proteinuria (protein in the urine) which results from the passage of parasite eggs through the bladder wall. Ultrasound scans of the urinary tract are also used to detect morbidity but are less practical in the majority of field settings owing to the requirement of specialized equipment and trained personnel. Current diagnosis of infection relies on detecting excreted eggs and excreted or circulating parasite products. Diagnostic methods include microscopic examination of eggs in urine (currently considered the gold standard), microscopic examination of tissue biopsies, serological and reagent strip diagnosis of circulating parasite proteins detectable in blood and urine and, more recently, detection of parasite DNA in urine or vaginal lavage samples. All currently used diagnostic methods have limitations associated with them. In particular, the gold standard microscopic enumeration of eggs in urine is less sensitive in low infections and does not detect single sex or prepatent infections, which makes it particularly inaccurate in young children harboring light infections and in older individuals with chronic infections who both excrete low levels of eggs. The detection of parasite DNA in urine samples by PCR described in the article by Ibironke et al. improves on this limitation. This article reviews the method described by Ibironke et al., compares it with current methods and discusses its potential use in field settings. PMID- 21973299 TI - Antimicrobial resistance in Neisseria gonorrhoeae in the UK: surveillance and management. AB - Successful antimicrobial therapy is fundamental to the public health control of gonorrhea, in the absence of a protective immune response. Neisseria gonorrhoeae, the causative agent, has presented a constant challenge for the provision of such therapy as it has demonstrated the ability to become resistant to successive highly active agents chosen for first-line treatment. Acquisition of plasmids from other bacteria and long-term use of a single agent has selected both single step high-level and low-level resistance due to multiple mutations. While therapeutic failure of the current recommended agents cefixime and ceftriaxone begins to emerge, choice of alternative therapies is limited. Guidelines for therapy will be dependent on surveillance programs but individual patient management will require a viable organism to detect emerging resistance. Advances in molecular detection, while advantageous for the diagnosis of gonorrhea, fail to provide a viable organism, posing even greater challenges for the definition of treatment failure, and appropriate end points for test of cure. Innovative and collaborative approaches will be essential to maintain gonorrhea as a treatable infection. PMID- 21973300 TI - Late HIV presentation: epidemiology, clinical implications and management. AB - Late presentation of HIV is common and is associated with several adverse outcomes including an increased risk of clinical progression, blunted immune recovery on highly active antiretroviral therapy and a greater risk of drug toxicity. Late presenters may have higher rates of poor adherence, exacerbated by the same factors that contribute to their late diagnosis, such as lack of knowledge about HIV and the benefits of highly active antiretroviral therapy. We review the definitions of, risk factors for and subsequent impact of late presentation. Evidence regarding how and when to start antiretroviral therapy, and with which agents, will be discussed, as well as issues surrounding vaccination and opportunistic infection prophylaxis for individuals with a low CD4 count. Finally, strategies to increase HIV testing uptake to reduce late presentation will be summarized. PMID- 21973301 TI - Hepatitis B virus infection: pathogenesis, reactivation and management in hematopoietic stem cell transplant recipients. AB - Hepatitis B virus (HBV) is a partially double stranded DNA virus that can integrate into host cell chromosomes as covalently closed circular DNA forms. HBV reactivation following hematopoietic stem cell transplantation in recipients with evidence of past HBV exposure, as well as exacerbation of a current HBV infection in HBV carrier recipients, secondary to chemotherapy and post-transplant immunosuppression that affect both humoral and cell-mediated control of HBV infection, are well documented in the literature. Management options include HBV DNA screening and antiviral prophylaxis. Nucleos(t)ide analogues have been used at the start of chemotherapy and pretransplantation, with the course continuing for 6 months. However, depending on the serum HBV-DNA level, the antiviral agent might be given until a therapeutic end point is reached. PMID- 21973302 TI - Staphylococcus lugdunensis: the coagulase-negative staphylococcus you don't want to ignore. AB - Staphylococcus lugdunensis is a virulent coagulase-negative staphylococcus (CoNS) that behaves like Staphylococcus aureus. Toxic shock syndrome, osteomyelitis, septic arthritis and postoperative endopthalmitis have been observed. Endocarditis complicated by heart failure, periannular abscess formation and embolic phenomenon have brought particular attention to this CoNS. Mortality rates for endocarditis appear higher when compared with other CoNS. Owing to the laboratory methods used, identification may be misleading. beta-lactam antimicrobials are recommended pending sensitivities. Evaluation for endocarditis should be pursued in bacteremic patients due to its pathogenic potential. PMID- 21973303 TI - Will new antimicrobials overcome resistance among Gram-negatives? AB - The spread of resistance among Gram-positive and Gram-negative bacteria represents a growing challenge for the development of new antimicrobials. The pace of antibiotic drug development has slowed during the last decade and, especially for Gram-negatives, clinicians are facing a dramatic shortage in the availability of therapeutic options to face the emergency of the resistance problem throughout the world. In this alarming scenario, although there is a shortage of compounds reaching the market in the near future, antibiotic discovery remains one of the keys to successfully stem and maybe overcome the tide of resistance. Analogs of already known compounds and new agents belonging to completely new classes of antimicrobials are in early stages of development. Novel and promising anti-Gram-negative antimicrobials belong both to old (cephalosporins, carbapenems, beta-lactamase inhibitors, monobactams, aminoglycosides, polymyxin analogues and tetracycline) and completely new antibacterial classes (boron-containing antibacterial protein synthesis inhibitors, bis-indoles, outer membrane synthesis inhibitors, antibiotics targeting novel sites of the 50S ribosomal subunit and antimicrobial peptides). However, all of these compounds are still far from being introduced into clinical practice. Therefore, infection control policies and optimization in the use of already existing molecules are still the most effective approaches to reduce the spread of resistance and preserve the activity of antimicrobials. PMID- 21973304 TI - Candida infections in non-neutropenic children after the neonatal period. AB - There are a variety of diseases, from local mucous membrane infections to invasive systemic infections, that are caused by Candida species. As a causative agent, Candida albicans is the most common; however, the other Candida species can also cause the same clinical syndromes. Most invasive fungal infections in children occur in the hospital setting. Candidemia is a serious condition associated with high morbidity and mortality and increased healthcare costs in pediatric patients. Children at the highest risk are those with prolonged intensive care unit stays, reduced immune function, recent surgery, prior bacterial infection, prior use of antibiotics and/or corticosteroids and other immunosuppressive agents, as well as use of a central venous catheter, total parenteral nutrition, mechanical ventilation and dialysis. Positive blood culture is the gold standard of candidemia; it should not be accepted as contamination or colonization in children with an intravascular catheter. However, in oropharyngeal or vulvovaginal candidiasis, culture of lesions is rarely indicated unless the disease is recalcitrant or recurrent. Recovery of Candida from the sputum should usually be considered as colonization and should not be treated with antifungal therapy. Antigen and antibody detecting tests are evaluated in invasive Candida infections; however, there are no published results in children, and their roles in diagnosis are also unclear. For the therapy of invasive Candida infections in non-neutropenic patients, fluconazole or an echinocandin is usually recommended. Alternatively, amphotericin B deoxycholate or lipid formulations of amphotericin B can also be used. The recommended therapy of Candida meningitis is amphotericin B combined with flucytosine. The combination therapy for Candida infections is usually not indicated. Prophylaxis in non neonatal, immunocompetent children is not recommended. PMID- 21973306 TI - Enhancement of mitomycin C-induced cytotoxicity by curcumin results from down regulation of MKK1/2-ERK1/2-mediated thymidine phosphorylase expression. AB - Curcumin (diferuloylmethane), a phenolic compound obtained from the rhizome of Curcuma longa, has been found to inhibit cell proliferation in various human cancer cell lines, including non-small cell lung cancer (NSCLC). Thymidine phosphorylase (TP) is considered an attractive therapeutic target, because increased TP expression can suppress cancer cell death induced by DNA-damaging agents. Mitomycin C (MMC), a chemotherapeutic agent used to treat NSCLC, inhibits tumour growth through DNA cross-linking and breaking. Whether MMC can affect TP expression in NSCLC is unknown. Therefore, in this study, we suggested that curcumin enhances the effects of MMC-mediated cytotoxicity by decreasing TP expression and ERK1/2 activation. Exposure of human NSCLC cell lines H1975 and H1650 to curcumin decreased MMC-elicited phosphorylated MKK1/2-ERK1/2 protein levels. Moreover, curcumin significantly decreased MMC-induced TP protein levels by increasing TP mRNA and protein instability. Enhancement of ERK1/2 activation by constitutively active MKK1/2 (MKK1/2-CA) increased TP protein levels and cell viability in curcumin- and MMC-co-treated cells. In contrast, U0126, a MKK1/2 inhibitor, augmented the cytotoxic effect and the down-regulation of TP by curcumin and MMC. Specific inhibition of TP by siRNA significantly enhanced MMC induced cell death and cell growth inhibition. Our results suggest that suppression of TP expression or administration of curcumin along with MMC may be a novel lung cancer therapeutic modality in the future. PMID- 21973307 TI - Depressive symptoms, substance use, and HIV-related high-risk behaviors among opioid-dependent individuals: results from the Clinical Trials Network. AB - The sample included 343 opioid-dependent adults enrolled in two national multisite studies of the National Drug Abuse Treatment Clinical Trials Network (CTN001-002). Opioid-dependent individuals were recruited from 12 sites across the United States from January 2001 to July 2002. We examined associations between depressive symptoms, co-occurring substance use (i.e., the use of substances other than opioids), and HIV-related sexual and injection risk behaviors. Data were collected using the Addiction Severity Index and the HIV Risk Behavior Scale, and analyzed using linear regression. Depressive symptoms were associated with an increased level of injection risk behaviors but were not associated with risky sexual behaviors. The co-occurring use of amphetamines also increased the likelihood of risky sexual behaviors. The study limitations and clinical implications are noted. The study was funded by the U.S. National Institute on Drug Abuse. PMID- 21973308 TI - Discovery of a protein-metabolite interaction between unsaturated fatty acids and the nuclear receptor Nur77 using a metabolomics approach. AB - Neuron-derived clone 77 (Nur77) is an orphan nuclear receptor with currently no known natural ligands. Here we applied a metabolomics platform for detecting protein-metabolite interactions (PMIs) to identify lipids that bind to Nur77. Using this approach, we discovered that the Nur77 ligand-binding domain (Nur77LBD) enriches unsaturated fatty acids (UFAs) in tissue lipid mixtures. The interaction of Nur77 with arachidonic acid and docosahexaenoic acid was subsequently characterized using a number of biophysical and biochemical assays. Together these data indicate that UFAs bind to Nur77LBD to cause changes in the conformation and oligomerization of the receptor. UFAs are the only endogenous lipids reported to bind to Nur77, which highlights the use of metabolomics in the discovery of novel PMIs. PMID- 21973309 TI - Circulating endothelial progenitor cells as potential prognostic biomarker in multiple myeloma. AB - Recent studies suggest that endothelial progenitor cells (EPCs) are mobilized from bone marrow to the peripheral circulation and aid in tumor neovascularization. In this study, circulating EPC (cEPC) numbers were assessed and correlation with clinical and laboratory parameters was determined in 75 patients with multiple myeloma (MM). Higher numbers of cEPCs (defined as CD45 /dim CD34+CD133+CD31+cells) were observed in MM as compared to healthy controls (n = 10; p < 0.001), which increased progressively from stage I to stage III (p < 0.001). A significant decline in cEPC numbers after therapy was observed in patients who attained at least a partial response (n = 47; p < 0.001). cEPCs correlated with response duration, at a baseline cut-off value of 19.6 cEPCs/MUL (p = 0.006) and 6.5 cEPCs/MUL after therapy (p < 0.001). This study suggests that cEPC numbers and changes in their levels may serve as a potential biomarker of disease severity, response to therapy and treatment outcome in MM. PMID- 21973310 TI - Immediate and delayed allergic hypersensitivity to corticosteroids: practical guidelines. AB - BACKGROUND: Corticosteroids (CS), anti-inflammatory drugs also widely used to treat various allergic diseases, may themselves give rise to immediate and delayed allergic hypersensitivity reactions. OBJECTIVES: To realise an appropriate diagnostic work-up in order to determine the CS-allergic patient's sensitization/tolerance profile and define the potential replacement agents that can still be tolerated. METHODS: Analysis of the patch test results and concomitant (cross-) reaction patterns obtained with 315 corticosteroid-allergic patients, as well as molecular modelling of molecules. RESULTS: Proposal of a simplified classification of corticosteroids as to their allergenic properties into 3 groups, determination of two patient profiles according to steric and electrostatic properties of the molecules. Conclusion. Practical information to the medical profession in order to detect and manage such reactions is provided. PMID- 21973312 TI - Length scales necessary for proper averaging to characterize polymerization in nanosystems: topochemical polymerization of diacetylene nanocrystals dispersed in a polystyrene matrix as probed by confocal Raman microscopy. AB - The scales necessary to make appropriate spatial averaging on solid-state polymerization were investigated by confocal Raman microscopy with a mapping resolution of 2 MUm. Nanocrystals of an aliphatic diacetylene with an average size of 0.14 MUm, each separated by 0.3 MUm on average, were dispersed in a polystyrene matrix and were polymerized by UV irradiation. The distribution of nanocrystals was inhomogeneous over approximately 20 MUm scale. A large crystal of the same monomer shows that photoinitiation is already averaged at the microscope resolution, while the color transition from the blue to the red form requires a scale greater than 5 MUm. For the nanocrystals at low conversion, UV vis absorption spectroscopy measured over a centimeter scale indicates linear polymerization kinetics and a higher polymer yield at a higher temperature. By contrast, the Raman microscopy reveals that, whereas the 20 MUm region of high monomer concentrations yields more polymers at -24 degrees C, the region of low monomer concentrations gives more polymers at 20 degrees C. We propose thermal initiation, which is not efficient in the large crystals, as an additional initiation process for the apparent discrepancy, implying that the initiation process is not averaged below 20 MUm scale for the dispersed nanocrystals. PMID- 21973311 TI - Differentiation of Populus species using chloroplast single nucleotide polymorphism (SNP) markers--essential for comprehensible and reliable poplar breeding. AB - Within the genus Populus several species belonging to different sections are cross-compatible. Hence, high numbers of interspecies hybrids occur naturally and, additionally, have been artificially produced in huge breeding programmes during the last 100 years. Therefore, determination of a single poplar species, used for the production of 'multi-species hybrids' is often difficult, and represents a great challenge for the use of molecular markers in species identification. Within this study, over 20 chloroplast regions, both intergenic spacers and coding regions, have been tested for their ability to differentiate different poplar species using 23 already published barcoding primer combinations and 17 newly designed primer combinations. About half of the published barcoding primers yielded amplification products, whereas the new primers designed on the basis of the total sequenced cpDNA genome of Populus trichocarpa Torr. & Gray yielded much higher amplification success. Intergenic spacers were found to be more variable than coding regions within the genus Populus. The highest discrimination power of Populus species was found in the combination of two intergenic spacers (trnG-psbK, psbK-psbl) and the coding region rpoC. In barcoding projects, the coding regions matK and rbcL are often recommended, but within the genus Populus they only show moderate variability and are not efficient in species discrimination. PMID- 21973313 TI - Nocebo in fibromyalgia: meta-analysis of placebo-controlled clinical trials and implications for practice. AB - BACKGROUND: Nocebo refers to adverse effects (AEs) generated by negative expectations that medical treatment will likely harm instead of heal and can be assessed in placebo-controlled randomized clinical trials (RCTs). We examined AEs following placebo administration in RCTs for fibromyalgia (FM), a condition characterized by patients' poor medication adherence, which may affect outcome and/or increase healthcare costs. METHODS: Following a systematic Medline search for RCTs for FM pharmacologic treatment published between 2001 and 2010, we assessed percentages of placebo-treated patients reporting at least one AE or discontinuing because of placebo intolerance and searched for factors influencing nocebo's extent. Percentages were compared with those revealed by similar meta analyses of RCTs for multiple sclerosis and primary headaches. RESULTS: Data were extracted from 16 RCTs fulfilling search criteria. Of 2026 placebo-treated patients, 67.2% (95%CI: 51.0-81.5%) reported at least one AE, and 9.5% (95%CI: 8.3-10.9%) discontinued placebo treatment because of intolerance. AEs in placebo arms corresponded quantitatively and qualitatively to those in active drug arms (rho > 0.88, P < 0.0001). Younger age and larger placebo arm size were associated with increased dropout rates. Patients with depression were more likely to withdraw from trials. Nocebo dropouts in FM trials were fourfold and twofold higher than in RCTs for multiple sclerosis treatment and migraine preventive treatment, respectively. CONCLUSIONS: Nocebo is remarkably prevalent in FM patients participating in RCTs. Because nocebo contributes to drug intolerance and treatment failure in clinical practice, identification of predisposing factors and efforts to prevent nocebo by educating these patients appropriately may be important for FM outcome. PMID- 21973314 TI - Treasures from the attic: transparencies digitally remastered and used for web based pathology training and education. PMID- 21973318 TI - Migraine and the presidency. AB - The disclosure that 2012 presidential candidate Michele Bachmann has migraines resulted in intense public and physician interest in the migraine of presidents, migraine and potential presidential disability, and the politics of migraine that are reviewed in this article. Jefferson had severe headaches that may have been a migraine variant. Lincoln, Grant, and Wilson were, John Adams and Eisenhower might have been, and Truman and Kennedy may have been migraineurs. First Ladies Abigail Adams, Lincoln, Eisenhower, and Kennedy all suffered from migraines. Although migraines can usually be effectively treated, disabling attacks could occur because of the accentuated triggers of office that could prevent a future president from being temporarily able to discharge the duties of office. The 25th amendment is available to voluntarily transfer powers of office to the vice president even for a short period of time. The current $13 million per year in research funding provided by the National Institutes of Health is clearly inadequate to the task of improving treatment for such a pervasive, disabling disease that so profoundly affects so many Americans including presidential candidates, presidents, and first ladies. A survey of the Southern Headache Society on migraine and presidential disability is also presented. PMID- 21973320 TI - Roles of DCL4 and DCL3b in rice phased small RNA biogenesis. AB - Higher plants have evolved multiple proteins in the RNase III family to produce and regulate different classes of small RNAs with specialized molecular functions. In rice (Oryza sativa), numerous genomic clusters are targeted by one of two microRNAs (miRNAs), miR2118 and miR2275, to produce secondary small interfering RNAs (siRNAs) of either 21 or 24 nucleotides in a phased manner. The biogenesis requirements or the functions of the phased small RNAs are completely unknown. Here we examine the rice Dicer-Like (DCL) family, including OsDCL1, -3a, -3b and -4. By deep sequencing of small RNAs from different tissues of the wild type and osdcl4-1, we revealed that the processing of 21-nucleotide siRNAs, including trans-acting siRNAs (tasiRNA) and over 1000 phased small RNA loci, was largely dependent on OsDCL4. Surprisingly, the processing of 24-nucleotide phased small RNA requires the DCL3 homolog OsDCL3b rather than OsDCL3a, suggesting functional divergence within DCL3 family. RNA ligase-mediated 5' rapid amplification of cDNA ends and parallel analysis of RNA ends (PARE)/degradome analysis confirmed that most of the 21- and 24-nucleotide phased small RNA clusters were initiated from the target sites of miR2118 and miR2275, respectively. Furthermore, the accumulation of the two triggering miRNAs requires OsDCL1 activity. Finally, we show that phased small RNAs are preferentially produced in the male reproductive organs and are likely to be conserved in monocots. Our results revealed significant roles of OsDCL4, OsDCL3b and OsDCL1 in the 21- and 24-nucleotide phased small RNA biogenesis pathway in rice. PMID- 21973321 TI - The water-soluble extract from cultured medium of Ganoderma lucidum (Reishi) mycelia (Designated as MAK) ameliorates murine colitis induced by trinitrobenzene sulphonic acid. AB - Ganoderma lucidum Karst is well known as 'Reishi', a traditional food in China and Japan. It contains a polysaccharide component known to induce granulocyte macrophage colony-stimulating factor (GM-CSF) production from murine splenocytes. Moreover, GM-CSF may be a therapeutic agent for Crohn's disease. In this study, we investigated the water-soluble, polysaccharide components of Reishi (designated as MAK) in murine colitis induced by trinitrobenzene sulphonic acid (TNBS). We examined the concentration of GM-CSF in peritoneal macrophage cells (PMs) of C57BL/6 mice during in vitro and in vivo stimulation with MAK. After feeding with chow or MAK for 2 weeks, 2 mg of TNBS/50% ethanol was administered to each mouse. After 3 days of TNBS treatment, intestinal inflammation was evaluated, and mononuclear cells of the mesenteric lymph nodes (MLNs) and colon were cultured for ELISA. To determine the preventive role of GM-CSF, the mice were pre-treated with or without anti-GM-CSF antibody before TNBS administration. In vitro and in vivo MAK-stimulated PMs produced GM-CSF in a dose-dependent manner. Intestinal inflammation by TNBS was improved by feeding with MAK. MLNs of mice treated with TNBS produced IFN-gamma, which was inhibited by feeding with MAK. In contrast, MLNs of mice treated with TNBS inhibited GM-CSF production, which was induced by feeding with MAK. The colon organ culture assay also revealed that IFN-gamma was decreased and GM-CSF was increased by MAK. The preventive effect was blocked by the neutralization of GM-CSF. We concluded that the induction of GM-CSF by MAK may provide the anti-inflammatory effect. PMID- 21973322 TI - Detection of Erwinia species from the apple and pear flora by mass spectroscopy of whole cells and with novel PCR primers. AB - AIMS: To detect the apple and pear pathogens Erwinia amylovora and Erwinia pyrifoliae as well as the related epiphytes Erwinia tasmaniensis and Erwinia billingiae, we created novel PCR primers and also applied them to a series of other plant-associated bacteria as control. To facilitate fast diagnosis, we used matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). METHODS AND RESULTS: The PCR primers were deduced from the pstS glmS regions, which can include the gene for levansucrase, and also from regions encoding capsular polysaccharide synthesis. All primer combinations were specific for their associated Erwinia species to detect them with conventional PCR, also in mixed cultures from necrotic plant tissue. Other primers designed for quantitative PCR with SYBR Green or together with TaqMan probes were applied for real-time detection to determine growth of Erw. amylovora, Erw. billingiae, Erw. pyrifoliae and Erw. tasmaniensis in apple blossoms. From whole-cell protein extracts, profiles were generated using a Bruker microflex machine and Erwinia strains classified according to a score scheme. CONCLUSIONS: The designed PCR primers identified the Erwinia species unambiguously and can be applied to qualitative and quantitative tests. MALDI-TOF MS data were in agreement with the PCR assays. SIGNIFICANCE AND IMPACT OF THE STUDY: The applied diagnosis methods allow fast and precise monitoring of two pathogenic and two epiphytic Erwinia species. They are valuable for population studies with apple and pear flowers and with diseased plant material. PMID- 21973323 TI - Effect of submicellar concentrations of conjugated and unconjugated bile salts on the lipid bilayer membrane. AB - The interaction of submicellar concentrations of various physiologically important unconjugated [sodium deoxycholate (NaDC), sodium cholate (NaC)] and conjugated [sodium glycodeoxycholate (NaGDC), sodium glycocholate (NaGC), sodium taurodeoxycholate (NaTDC), sodium taurocholate (NaTC)] bile salts with dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphatidylcholine (DMPC) small unilamellar vesicles in solid gel (SG) and liquid crystalline (LC) phases was investigated using the excited-state prototropism of 1-naphthol. Steady-state and time-resolved fluorescence of the two excited-state prototropic forms of 1 naphthol indicate that submicellar bile salt concentration induces hydration of the lipid bilayer membrane into the core region. This hydration effect is a general phenomenon of the bile salts studied. The bilayer hydration efficiency of the bile salt follows the order NaDC > NaC > NaGDC > NaTDC > NaGC > NaTC for both DPPC and DMPC vesicles in their SG and LC phases. PMID- 21973324 TI - d -> f energy transfer in a series of Ir(III)/Eu(III) dyads: energy-transfer mechanisms and white-light emission. AB - An extensive series of blue-luminescent iridium(III) complexes has been prepared containing two phenylpyridine-type ligands and one ligand containing two pyrazolylpyridine units, of which one is bound to Ir(III) and the second is pendant. Attachment of {Ln(hfac)(3)} (Ln = Eu, Gd; hfac = anion of 1,1,1,5,5,5, hexafluoropentanedione) to the second coordination site affords Ir(III)/Ln(III) dyads. Crystallographic analysis of several mononuclear iridium(III) complexes and one Ir(III)/Eu(III) dyad reveals that in most cases the complexes can adopt a folded conformation involving aromatic pi stacking between a phenylpyridine ligand and the bis(pyrazolylpyridine) ligand, but in one series, based on CF(3) substituted phenylpyridine ligands coordinated to Ir(III), the steric bulk of the CF(3) group prevents this and a quite different and more open conformation arises. Quantum mechanical calculations well reproduce these two types of "folded" and "open" conformations. In the Ir(III)/Eu(III) dyads, Ir -> Eu energy transfer occurs with varying degrees of efficiency, resulting in partial quenching of the Ir(III)-based blue emission and the appearance of a sensitized red emission from Eu(III). Calculations based on consideration of spectroscopic overlap integrals rule out any significant contribution from Forster (dipole dipole) energy transfer over the distances involved but indicate that Dexter-type (exchange) energy transfer is possible if there is a small electronic coupling that would arise, in part, through pi stacking between components. In some cases, an initial photoinduced electron-transfer step could also contribute to Ir -> Eu energy transfer, as shown by studies on isostructural iridium/gadolinium model complexes. A balance between the blue (Ir-based) and red (Eu-based) emission components can generate white light. PMID- 21973325 TI - Manipulation of VOC emissions with methyl jasmonate and carrageenan in the evergreen conifer Pinus sylvestris and evergreen broadleaf Quercus ilex. AB - Plant defence can be induced by exposing plants to the plant hormone jasmonic acid (JA) or its volatile ester, methyl jasmonate (MeJA). Carrageenans (Carr) - sulphated D-galactans extracted from red algae - can also induce plant defences. In this study, the effects of exogenous MeJA and Carr application (concentration 300 and 12.7 MUmol, respectively) on volatile emissions from two widespread evergreen woody species, Pinus sylvestris (nine Turkish and one Finnish provenance) and Quercus ilex (Italian provenance) were investigated. We collected headspace samples from seedlings and analysed the quality and quantity of volatile compounds emitted by treated and control plants. In total, 19 monoterpenes, 10 sesquiterpenes, 10 green leaf volatiles (GLVs) and two aromatic compounds were emitted by P. sylvestris from all the provenances studied. Foliar MeJA application clearly affected the volatile profiles of trees from all the provenances. Effects of Carr were genotype specific. In Q. ilex, emissions of sesquiterpenes, GLVs and the homoterpene (E)-DMNT were all induced by MeJA application. However, emissions of most constitutively emitted monoterpenes were significantly reduced. Carr application also led to a significant reduction in monoterpene emissions, but without corresponding increases in other emissions. Our results indicate that exogenously applied MeJA and Carr can both significantly modify the volatile profiles of P. sylvestris and Q. ilex, but also that there are important provenance- and species-specific differences in the overall degree of elicitation and compositions of elicited compounds. PMID- 21973326 TI - Seed longevity and fire: germination responses of an exotic perennial herb in NW Patagonian grasslands (Argentina). AB - Fire affects grassland composition by selectively influencing recruitment. Some exotic species can increase their abundance as a consequence of fire-stimulated seed germination, but response may depend on seed age. Rumex acetosella L. (Polygonaceae, sheep's sorrel) is a cosmopolitan herb that has invaded NW Patagonia's grasslands. This species forms persistent soil seed banks and increases after disturbances, particularly fire. We studied how fire and seed longevity influence R. acetosella germination. In 2008, we conducted laboratory experiments where we exposed different-aged seeds (up to 19 years old) to heat, smoke, charcoal, ash and control treatments. Total percentage germination and mean germination time depended on both seed age and fire treatment. Germination of younger seeds decreased with increasing temperature. There was no general pattern in germination responses of different-aged seeds to smoke, charcoal and ash. While smoke improved the germination of fresh seeds, charcoal decreased germination. Germination of untreated seeds was negatively correlated with seed age, and mean germination time increased with seed age. In most treatments, fresh seeds had lower germination than 1-5-year-old seeds, indicating an after-ripening requirement. Smoke stimulates R. acetosella germination, causing successful recruitment during post-fire conditions. Fresh seeds are particularly responsive to fire factors, possibly because they have not experienced physical degradation and are more receptive to environmental stimuli. Knowing the colonisation potential from the soil seed bank of this species during post-fire conditions will allow us to predict their impact on native communities. PMID- 21973328 TI - Ultrastructural features of nevus comedonicus. PMID- 21973327 TI - Diagnostic yield and economic implications of endoscopic colonic biopsies in patients with chronic diarrhoea. AB - AIMS: Random colonic biopsies are recommended to exclude microscopic colitis in patients with chronic diarrhoea especially when mucosa is macroscopically normal at endoscopy. This study aimed to assess the clinical outcome and economic impact of such a policy in an unselected group of patients with macroscopically normal mucosa. METHODS: All new patients undergoing colonoscopy for investigation of chronic diarrhoea between April and December 2009 were included. Patients were divided into two groups: macroscopically normal mucosa and macroscopically inflamed mucosa. Endoscopic findings were correlated with histology of random biopsies and haematological parameters. Symptom status and any treatment were established from follow-up. The breakdown and overall cost of random biopsies for each patient with a macroscopically normal mucosa were determined, and cost incurred per diagnosis of microscopic colitis was established. RESULTS: Altogether 137 (90.1%) of 152 patients with chronic diarrhoea had macroscopically normal mucosa at colonoscopy. Overall incidence of microscopic colitis in the study was 1.3% (2/152); both patients belonged to the macroscopically normal mucosa group. At follow-up, both these patients had spontaneous symptom resolution without any specific treatment. The policy of undertaking random biopsies in patients with macroscopically normal mucosa incurred an extra cost of L22,057 to diagnose two cases of microscopic colitis but did not alter medical treatment. CONCLUSIONS: In unselected patients with chronic diarrhoea and macroscopically normal mucosa, random colonic biopsies have a low diagnostic yield and incur a high cost. Continued research for predictive markers to improve patient selection for targeted biopsies is needed to develop a cost-effective investigative algorithm in chronic diarrhoea. PMID- 21973329 TI - Prevalence of Dental Anomalies in Patients With Nonsyndromic Cleft Lip and/or Palate in a Brazilian Population. AB - Objective : Many studies have demonstrated a high frequency of dental anomalies in patients with cleft lip and/or palate. Because dental anomalies may complicate dental treatment, we investigated the prevalence of dental anomalies in a group of Brazilian patients with nonsyndromic cleft lip and/or palate. Design, Participants, Setting : Retrospective analysis was performed using clinical records of 296 patients aged between 12 and 30 years with repaired nonsyndromic cleft lip and/or palate without history of tooth extraction and orthodontic treatment. Associations between oral clefts and presence of dental anomalies outside the cleft area were investigated. Results : Dental anomalies were identified in 39.9% of the nonsyndromic cleft lip and/or palate patients, and tooth agenesis (47.5%), impacted tooth (13.1%), and microdontia (12.7%) were the most common anomalies. Cleft lip patients were less affected by dental anomalies compared with cleft palate or cleft lip and palate patients (p = .057). Specifically, patients with unilateral cleft lip and palate were significantly more affected by dental anomalies than those with bilateral cleft lip and palate (p = .00002), and individuals with unilateral complete cleft lip and palate (p = .002) and complete cleft palate (p = .01) were significantly more affected by tooth agenesis than other cleft types. Agenesis of the premolars (p = .043) and maxillary lateral incisors (p = .03) were significantly more frequent in patients with unilateral complete cleft lip and palate. Conclusions : The present study revealed a high frequency of dental anomalies in nonsyndromic cleft lip and/or palate patients and further demonstrated that patients with unilateral cleft lip and palate were frequently more affected by dental anomalies than those with bilateral cleft lip and palate. Moreover, our results demonstrate that dental anomalies should be considered during dental treatment planning for individuals affected by nonsyndromic cleft lip and/or palate. PMID- 21973330 TI - Harvesting mechanical energy via structural vibrations. PMID- 21973331 TI - Ambient noise in large rivers (L). AB - This paper presents the results of hydroacoustic noise research in three large European rivers: the Danube, the Sava, and the Tisa. Noise in these rivers was observed during a period of ten years, which includes all annual variation in hydrological and meteorological conditions (flow rate, speed of flow, wind speed, etc.). Noise spectra are characterized by wide maximums at frequencies between 20 and 30 Hz, and relatively constant slope toward higher frequencies. Spectral level of noise changes in time in relatively wide limits. At low frequencies, below 100 Hz, the dynamics of noise level is correlated with the dynamics of water flow and speed. At higher frequencies, noise spectra are mostly influenced by human activities on river and on riverbanks. The influence of wind on noise in rivers is complex due to the annual variation of river surface. The influence of wind is less pronounced than in oceans, seas, and lakes. PMID- 21973332 TI - An iterative method to solve acoustic scattering problems using a boundary integral equation. AB - In this work, a simple iterative method to solve the acoustic scattering/radiation problems using the boundary integral equation (BIE) formulation is presented. The operator equation obtained in the BIE formulation is converted into a matrix equation using the well-known method of moments solution procedure. The present method requires much fewer mathematical operations per iteration when compared to other available iterative methods. Further, the present iterative method can easily handle multiple incident fields, a highly desirable feature not available in any other iterative method, much the same way as direct solution techniques. Several numerical examples are presented to illustrate the efficiency and accuracy of the method. PMID- 21973333 TI - Experiments on stress dependent borehole acoustic waves. AB - In the laboratory setup, a borehole traverses a dry sandstone formation, which is subjected to a controlled uniaxial stress in the direction perpendicular to the borehole axis. Measurements are made in a single loading-unloading stress cycle from zero to 10 MPa and then back down to zero stress. The applied stress and the presence of the borehole induce anisotropy in the bulk of the material and stress concentration around the borehole, both azimuthally and radially. Acoustic waves are generated and detected in the water-filled borehole, including compressional and shear headwaves, as well as modes of monopole, dipole, quadrupole, and higher order azimuthal symmetries. The linear and non-linear elastic parameters of the formation material are independently quantified, and utilized in conjunction with elastic theories to predict the characteristics of various borehole waves at zero and finite stress conditions. For example, an analytic theory is developed which is successfully used to estimate the changes of monopole tube mode at low frequency resulted from uniaxial stress, utilizing the measured material third order elasticity parameters. Comparisons between various measurements as well as that between experiments and theories are also presented. PMID- 21973334 TI - The feasibility of pulse compression by nonlinear effective bandwidth extension. AB - Chirp-encoded excitation has been utilized for increased signal-to-noise ratio (SNR) in both linear and harmonic imaging. In either case, it is necessary to isolate the relevant frequency band to avoid artifacts. In contrast, the present study isolates and then combines the fundamental and the higher harmonics, treating them as a single, extended bandwidth. Pulse-inverted sum and difference signals are first used to isolate even and odd harmonics. Matched filters specific to the source geometry and the transmit signal are then separately applied to each harmonic band. Verification experiments are performed using up to the third harmonic resulting from an underwater chirp excitation. Analysis of signal peaks after scattering from a series of steel and nylon wires indicates increased compression using the extended bandwidth, as compared to well established methods for fundamental and second harmonic chirp compression. Using third harmonic bands, a mean pulse width of 56% relative to fundamental compression and 48% relative to second harmonic compression was observed. Further optimization of the compression by altering the transmission indicated 17% additional reduction in the pulse width and a 47% increase in peak-to-sidelobe ratio. Overall, results establish the feasibility of extended bandwidth signal compression for simultaneously increasing SNR and signal resolution. PMID- 21973335 TI - Nonlinear shear wave interaction at a frictional interface: energy dissipation and generation of harmonics. AB - Analytical and numerical modeling of the nonlinear interaction of shear wave with a frictional interface is presented. The system studied is composed of two homogeneous and isotropic elastic solids, brought into frictional contact by remote normal compression. A shear wave, either time harmonic or a narrow band pulse, is incident normal to the interface and propagates through the contact. Two friction laws are considered and the influence on interface behavior is investigated: Coulomb's law with a constant friction coefficient and a slip weakening friction law which involves static and dynamic friction coefficients. The relationship between the nonlinear harmonics and the dissipated energy, and the dependence on the contact dynamics (friction law, sliding, and tangential stress) and on the normal contact stress are examined in detail. The analytical and numerical results indicate universal type laws for the amplitude of the higher harmonics and for the dissipated energy, properly non-dimensionalized in terms of the pre-stress, the friction coefficient and the incident amplitude. The results suggest that measurements of higher harmonics can be used to quantify friction and dissipation effects of a sliding interface. PMID- 21973336 TI - Baseline-free estimation of residual fatigue life using a third order acoustic nonlinear parameter. AB - Prediction of crack growth and fatigue life estimation of metals using linear/nonlinear acousto-ultrasound methods is an ongoing issue. It is known that by measuring nonlinear parameters, the relative accumulated fatigue damage can be evaluated. However, there is still a need to measure two crack propagation states to assess the absolute residual fatigue life. A procedure based on the measurement of a third-order acoustic nonlinear parameter is presented to assess the residual fatigue life of a metallic component without the need of a baseline. The analytical evaluation of how the cubic nonlinear-parameter evolves during crack propagation is presented by combining the Paris law to the Nazarov-Sutin crack equation. Unlike other developed models, the proposed model assumes a crack surface topology with variable geometrical parameters. Measurements of the cubic nonlinearity parameter on AA2024-T351 specimens demonstrated high sensitivity to crack propagation and excellent agreement with the predicted theoretical behavior. The advantages of using the cubic nonlinearity parameter for fatigue cracks on metals are discussed by comparing the relevant results of a quadratic nonlinear parameter. Then the methodology to estimate crack size and residual fatigue life without the need of a baseline is presented, and advantages and limitations are discussed. PMID- 21973337 TI - Elimination of standing wave effects in ultrasound radiation force excitation in air using random carrier frequency packets. AB - The ultrasound radiation force has been used for noncontact excitation of devices ranging from microcantilevers to acoustic guitars. For ultrasound radiation force excitation, one challenge is formation of standing waves between the ultrasound transducer and the device under test. Standing waves result in constructive/destructive interference causing significant variations in the intensity of the ultrasound field. The standing-wave induced intensity variations in the radiation force can result from minor changes in the transducer position, carrier frequency, or changes in the speed of sound due to changes in ambient temperature. The current study demonstrates that by randomly varying the ultrasound carrier frequency in packets, it is possible to eliminate the negative consequences resulting from the formation of standing waves. A converging ultrasound transducer with a central frequency of 550 kHz was focused onto a brass cantilever. The 267 Hz resonance was excited with the ultrasound radiation force with a carrier frequency that randomly varied between 525 kHz to 575 kHz in packets of 10 cycles. Because each packet had a different carrier frequency, the amplitude of standing wave artifacts was reduced by a factor of 20 compared to a constant frequency excitation of 550 kHz. PMID- 21973338 TI - Effect of randomly varying impedance on the interference of the direct and ground reflected waves. AB - A randomly varying ground impedance is introduced into the solution for the sound field produced by a point source in a homogeneous atmosphere above a flat ground. The results show that in general the ground with a random impedance cannot be represented by an effective, non-random impedance. The behavior of the solution is studied with a relaxation model for the impedance in which porosity and the static flow resistivity are random variables. Mean values and standard deviations are adopted from measurements of two types of ground surfaces. For both surfaces, the mean intensity of the sound field above a random-impedance ground deviates only slightly from the intensity above a non-random impedance. The normalized standard deviation of intensity fluctuations can, however, be greater than one, thus indicating that for a particular realization of the random impedance, the sound intensity might significantly deviate from the intensity for a non-random impedance. PMID- 21973339 TI - Experimental study of the influence of low frequency flow modulation on the whistling behavior of a corrugated pipe. AB - It is well known that airflow in a corrugated pipe can excite whistling at the frequencies of the pipe's longitudinal acoustic modes. This short contribution reports on the results of experiments where a low frequency, oscillating flow with velocity magnitudes of the same order as the airflow has been added. Depending on the oscillation strength, it has been found that this flow may silence the pipe or move the whistling to higher harmonics. It is also shown that the low frequency oscillation itself may excite higher frequency whistling sounds in the pipe. PMID- 21973340 TI - The relative effects of particles and turbulence on acoustic scattering from deep sea hydrothermal vent plumes. AB - Acoustic methods are applied to the investigation and monitoring of a vigorous hydrothermal plume within the Main Endeavor vent field at the Endeavor segment of the Juan de Fuca Ridge. Forward propagation and scattering from suspended particulates using Rayleigh scattering theory is shown to be negligible (log amplitude variance sigma(chi) (2)~10(-7)) compared to turbulence induced by temperature fluctuations (sigma(chi) (2)~0.1). The backscattering from turbulence is then quantified using the forward scattering derived turbulence level, which gives a volume backscattering strength of s(V)=6.5 * 10(-8) m(-1). The volume backscattering cross section from particulates can range from s(V)=3.3 * 10(-6) to 7.2 * 10(-10) m(-1) depending on the particle size. These results show that forward scatter acoustic methods in hydrothermal vent applications can be used to quantify turbulence and its effect on backscatter measurements, which can be a dominant factor depending on the particle size and its location within the plume. PMID- 21973341 TI - Localization and source level estimates of black drum (Pogonias cromis) calls. AB - A four hydrophone linear array was used to localize calling black drum and estimate source levels and signal propagation. A total of 1025 source level estimates averaged 165 dB(RMS) relative (re:) 1 MUPa (standard deviation (SD)=1.0). The authors suggest that the diverticulated morphology of the black drum swimbladder increase the bladder's surface area, thus contributing to sound amplitude. Call energy was greatest in the fundamental frequency (94 Hz) followed by the second (188 Hz) and third harmonics (282 Hz). A square root model best described propagation of the entire call, and separately the fundamental frequency and second harmonic. A logarithmic model best described propagation of the third harmonic which was the only component to satisfy the cut-off frequency equation. Peak auditory sensitivity was 300 Hz at a 94 dB re: 1 MUPa threshold based on auditory evoked potential measurements of a single black drum. Based on mean RMS source level, signal propagation, background levels, and hearing sensitivity, the communication range of black drum was estimated at 33-108 m and was limited by background levels not auditory sensitivity. This estimate assumed the source and receiver were at approximately 0.5 m above the bottom. Consecutive calls of an individual fish localized over 59 min demonstrated a mean calling period of 3.6 s (SD=0.48), mean swimming speed of 0.5 body lengths/s, and a total distance swam of 1035 m. PMID- 21973342 TI - Phase calibration of sonar systems using standard targets and dual-frequency transmission pulses. AB - The phase angle component of the complex frequency response of a sonar system operating near transducer resonance is usually distorted. Interpretation and classification of the received sonar signal benefits from the preservation of waveform fidelity over the full bandwidth. A calibration process that measures the phase response in addition to the amplitude response is thus required. This paper describes an extension to the standard-target calibration method to include phase angle, without affecting the experimental apparatus, by using dual frequency transmission pulses and frequency-domain data processing. This approach reduces the impact of unknown range and sound speed parameters upon phase calibration accuracy, as target phase is determined from the relationship of the two frequency components instead of relying on a local phase reference. Tungsten carbide spheres of various sizes were used to simultaneously calibrate the amplitude and phase response of an active sonar system in a laboratory tank. Experimental measurements of target phase spectra are in good agreement with values predicted from a theoretical model based upon full-wave analysis, over an operating frequency of 50-125 kHz. PMID- 21973343 TI - Cavitation clouds created by shock scattering from bubbles during histotripsy. AB - Histotripsy is a therapy that focuses short-duration, high-amplitude pulses of ultrasound to incite a localized cavitation cloud that mechanically breaks down tissue. To investigate the mechanism of cloud formation, high-speed photography was used to observe clouds generated during single histotripsy pulses. Pulses of 5-20 cycles duration were applied to a transparent tissue phantom by a 1-MHz spherically focused transducer. Clouds initiated from single cavitation bubbles that formed during the initial cycles of the pulse, and grew along the acoustic axis opposite the propagation direction. Based on these observations, we hypothesized that clouds form as a result of large negative pressure generated by the backscattering of shockwaves from a single bubble. The positive-pressure phase of the wave inverts upon scattering and superimposes on the incident negative-pressure phase to create this negative pressure and cavitation. The process repeats with each cycle of the incident wave, and the bubble cloud elongates toward the transducer. Finite-amplitude propagation distorts the incident wave such that the peak-positive pressure is much greater than the peak negative pressure, which exaggerates the effect. The hypothesis was tested with two modified incident waves that maintained negative pressure but reduced the positive pressure amplitude. These waves suppressed cloud formation which supported the hypothesis. PMID- 21973344 TI - A frequency selective acoustic transducer for directional Lamb wave sensing. AB - A frequency selective acoustic transducer (FSAT) is proposed for directional sensing of guided waves. The considered FSAT design is characterized by a spiral configuration in wavenumber domain, which leads to a spatial arrangement of the sensing material producing output signals whose dominant frequency component is uniquely associated with the direction of incoming waves. The resulting spiral FSAT can be employed both for directional sensing and generation of guided waves, without relying on phasing and control of a large number of channels. The analytical expression of the shape of the spiral FSAT is obtained through the theoretical formulation for continuously distributed active material as part of a shaped piezoelectric device. Testing is performed by forming a discrete array through the points of the measurement grid of a scanning laser Doppler vibrometer. The discrete array approximates the continuous spiral FSAT geometry, and provides the flexibility to test several configurations. The experimental results demonstrate the strong frequency dependent directionality of the spiral FSAT and suggest its application for frequency selective acoustic sensors, to be employed for the localization of broadband acoustic events, or for the directional generation of Lamb waves for active interrogation of structural health. PMID- 21973345 TI - Modeling and analysis of multiple scattering of acoustic waves in complex media: application to the trabecular bone. AB - The integral equations that describe scattering in the media with step-rise changing parameters have been numerically solved for the trabecular bone model. The model consists of several hundred discrete randomly distributed elements. The spectral distribution of scattering coefficients in subsequent orders of scattering has been presented. Calculations were carried on for the ultrasonic frequency ranging from 0.5 to 3 MHz. Evaluation of the contribution of the first, second, and higher scattering orders to total scattering of the ultrasounds in trabecular bone was done. Contrary to the approaches that use the MUCT images of trabecular structure to modeling of the ultrasonic wave propagation condition, the 3D numerical model consisting of cylindrical elements mimicking the spatial matrix of trabeculae, was applied. The scattering, due to interconnections between thick trabeculae, usually neglected in trabecular bone models, has been included in calculations when the structure backscatter was evaluated. Influence of the absorption in subsequent orders of scattering is also addressed. Results show that up to 1.5 MHz, the influence of higher scattering orders on the total scattered field characteristic can be neglected while for the higher frequencies, the relatively high amplitude interference peaks in higher scattering orders clearly occur. PMID- 21973346 TI - Phase-controlling phononic crystals: realization of acoustic Boolean logic gates. AB - A phononic crystal (PC) consisting of a square array of cylindrical polyvinylchloride inclusions in air is used to construct a variety of acoustic logic gates. In a certain range of operating frequencies, the PC band structure shows square-like equi-frequency contours centered off the gamma point. This attribute allows for the realization of non-collinear wave and group velocity vectors in the PC wave vector space. This feature can be utilized to control with great precision, the relative phase between propagating acoustic waves in the PC. By altering the incidence angle of the impinging acoustic beams or varying the PC thickness, interferences occur between acoustic wave pairs. It is recognized that information can be encoded with this mechanism (e.g., wave amplitudes/interference patterns) and accordingly to construct a series of logic gates emulating Boolean functions. The NAND, XOR, and NOT gates are demonstrated with finite-difference time-domain simulations of acoustic waves impinging upon the PC. PMID- 21973347 TI - Investigation of spherical loudspeaker arrays for local active control of sound. AB - Active control of sound can be employed globally to reduce noise levels in an entire enclosure, or locally around a listener's head. Recently, spherical loudspeaker arrays have been studied as multiple-channel sources for local active control of sound, presenting the fundamental theory and several active control configurations. In this paper, important aspects of using a spherical loudspeaker array for local active control of sound are further investigated. First, the feasibility of creating sphere-shaped quiet zones away from the source is studied both theoretically and numerically, showing that these quiet zones are associated with sound amplification and poor system robustness. To mitigate the latter, the design of shell-shaped quiet zones around the source is investigated. A combination of two spherical sources is then studied with the aim of enlarging the quiet zone. The two sources are employed to generate quiet zones that surround a rigid sphere, investigating the application of active control around a listener's head. A significant improvement in performance is demonstrated in this case over a conventional headrest-type system that uses two monopole secondary sources. Finally, several simulations are presented to support the theoretical work and to demonstrate the performance and limitations of the system. PMID- 21973348 TI - Urban road traffic noise and annoyance: the effect of a quiet facade. AB - Road traffic noise in urban areas is a major source of annoyance. A quiet facade has been hypothesized to beneficially affect annoyance. However, only a limited number of studies investigated this hypothesis, and further quantification is needed. This study investigates the effect of a relatively quiet facade on the annoyance response. Logistic regression was performed in a large population based study (GLOBE, N~18,000), to study the association between road traffic noise exposure at the most exposed dwelling facade (L(den)) and annoyance in: (1) The subgroup with a relatively quiet facade (large difference in road traffic noise level between most and least exposed facade (Q>10 dB); (2) the subgroup without a relatively quiet facade (Q<10 dB). Questionnaire data were linked to individual exposure assessment based on detailed spatial data (GIS) and standard modeling techniques. Annoyance was less likely (OR(Q) (>10)=4-6) number of receivers. PMID- 21973355 TI - Acoustic centering of sources measured by surrounding spherical microphone arrays. AB - The radiation patterns of acoustic sources have great significance in a wide range of applications, such as measuring the directivity of loudspeakers and investigating the radiation of musical instruments for auralization. Recently, surrounding spherical microphone arrays have been studied for sound field analysis, facilitating measurement of the pressure around a sphere and the computation of the spherical harmonics spectrum of the sound source. However, the sound radiation pattern may be affected by the location of the source inside the microphone array, which is an undesirable property when aiming to characterize source radiation in a unique manner. This paper presents a theoretical analysis of the spherical harmonics spectrum of spatially translated sources and defines four measures for the misalignment of the acoustic center of a radiating source. Optimization is used to promote optimal alignment based on the proposed measures and the errors caused by numerical and array-order limitations are investigated. This methodology is examined using both simulated and experimental data in order to investigate the performance and limitations of the different alignment methods. PMID- 21973356 TI - Data completion method for the characterization of sound sources. AB - This paper presents a different approach to solve the inverse acoustic problem. This problem is an "ill-posed" problem since the solution is very sensitive to measurement precision. A classical way to solve this problem consists in inversing a propagation operator which relates structure quantities (acoustic pressures or gradients) to near-field quantities (acoustic pressures or gradients). This can be achieved by using near-field acoustical holography (NAH) in separable coordinate systems. In order to overcome this limitation, the inverse boundary element method (IBEM) can be implemented to recover all acoustic quantities in a three-dimensional space and on an arbitrary three-dimensional source surface. In this paper, the data completion method (DCM) is developed: the acoustic gradients and pressures are known on a surface surrounding the source, but are unknown on its structure. The solution is given by the resolution of the Helmholtz formulation applied on the empty domain between the two boundaries made by the measurements quantities and the structure of the source. The conventional method applies directly the integral formulation for the empty domain. Another way of solving this Helmholtz formulation can be achieved by splitting it in two well-posed subproblems in a Steklov-Poincare's formulation. The data completion method allows one to solve the problem with acoustic perturbations due to sources on the exterior domain, or due to a confined domain, without altering the results. PMID- 21973357 TI - Time-reversal multiple signal classification in case of noise: a phase-coherent approach. AB - The problem of locating point-like targets beyond the classical resolution limit is revisited. Although time-reversal MUltiple SIgnal Classification (MUSIC) is known for its super-resolution ability in localization of point scatterers, in the presence of noise this super-resolution property will easily break down. In this paper a phase-coherent version of time-reversal MUSIC is proposed, which can overcome this fundamental limit. The algorithm has been tested employing synthetic multiple scattering data based on the Foldy-Lax model, as well as experimental ultrasound data acquired in a water tank. Using a limited frequency band, it was demonstrated that the phase-coherent MUSIC algorithm has the potential of giving significantly better resolved scatterer locations than standard time-reversal MUSIC. PMID- 21973358 TI - Direct analysis of dispersive wave fields from near-field pressure measurements. AB - Flexural waves play a significant role for the radiation of sound from plates. The analysis of flexural wave fields enables the detection of sources and transmission paths in plate-like structures. The measurement of these wave fields can be carried out indirectly by means of near-field acoustic holography, which determines the vibrational wave field from pressure information measured in a plane close to the plate under investigation. The reconstruction of the plate vibration is usually obtained by inverting the forward radiation problem, i.e., by inversion of an integral operator. In this article, it is shown that a pressure measurement taken in the extreme near-field of a vibrating plate can directly be used for the approximate analysis of the dispersive flexural wave field. The inversion step of near-field acoustic holography is not necessarily required if such an approximate solution is sufficient. The proposed method enables fast and simple analysis of dispersion characteristics. Application of dispersion compensation to the measured field allows for visualizations of propagating wavefronts, such that sources and scatterers in the plate can be detected. The capabilities of the described approach are demonstrated on several measurements. PMID- 21973359 TI - Masker location uncertainty reveals evidence for suppression of maskers in two talker contexts. AB - In many natural settings, spatial release from masking aids speech intelligibility, especially when there are competing talkers. This paper describes a series of three experiments that investigate the role of prior knowledge of masker location on phoneme identification and spatial release from masking. In contrast to previous work, these experiments use initial stop consonant identification as a test of target intelligibility to ensure that listeners had little time to switch the focus of spatial attention during the task. The first experiment shows that target phoneme identification was worse when a masker played from an unexpected location (increasing the consonant identification threshold by 2.6 dB) compared to when an energetically very similar and symmetrically located masker came from an expected location. In the second and third experiments, target phoneme identification was worse (increasing target threshold levels by 2.0 and 2.6 dB, respectively) when the target was played unexpectedly on the side from which the masker was expected compared to when the target came from an unexpected, symmetrical location in the hemifield opposite the expected location of the masker. These results support the idea that listeners modulate spatial attention by both focusing resources on the expected target location and withdrawing attentional resources from expected locations of interfering sources. PMID- 21973360 TI - Fundamental frequency is critical to speech perception in noise in combined acoustic and electric hearing. AB - Cochlear implant (CI) users have been shown to benefit from residual low frequency hearing, specifically in pitch related tasks. It remains unclear whether this benefit is dependent on fundamental frequency (F0) or other acoustic cues. Three experiments were conducted to determine the role of F0, as well as its frequency modulated (FM) and amplitude modulated (AM) components, in speech recognition with a competing voice. In simulated CI listeners, the signal-to noise ratio was varied to estimate the 50% correct response. Simulation results showed that the F0 cue contributes to a significant proportion of the benefit seen with combined acoustic and electric hearing, and additionally that this benefit is due to the FM rather than the AM component. In actual CI users, sentence recognition scores were collected with either the full F0 cue containing both the FM and AM components or the 500-Hz low-pass speech cue containing the F0 and additional harmonics. The F0 cue provided a benefit similar to the low-pass cue for speech in noise, but not in quiet. Poorer CI users benefited more from the F0 cue than better users. These findings suggest that F0 is critical to improving speech perception in noise in combined acoustic and electric hearing. PMID- 21973361 TI - Psychoacoustic evaluation of multichannel reproduced sounds using binaural synthesis and spherical beamforming. AB - The binaural auralization of a 3D sound field using spherical-harmonics beamforming (SHB) techniques was investigated and compared with the traditional method using a head-and-torso simulator (HATS). The new procedure was verified by comparing simulated room impulse responses with measured ones binaurally. The objective comparisons show that there is good agreement in the frequency range between 0.1 and 6.4 kHz. A listening experiment was performed to validate the SHB method subjectively and to compare it to the HATS method. Two musical excerpts, pop and classical, were used. Subjective responses were collected in two head rotation conditions (fixed and rotating) and six spatial reproduction modes, including phantom mono, stereo, and surround sound. The results show that subjective scales of width, spaciousness, and preference based on the SHB method were similar to those obtained for the HATS method, although the width and spaciousness of the stimuli processed by the SHB method were judged slightly higher than the ones using the HATS method in general. Thus, binaural synthesis using SHB may be a useful tool to reproduce a 3D sound field binaurally, while saving considerably on measurement time because head rotation can be simulated based on a single recording. PMID- 21973362 TI - Perception of interrupted speech: effects of dual-rate gating on the intelligibility of words and sentences. AB - Perception of interrupted speech and the influence of speech materials and memory load were investigated using one or two concurrent square-wave gating functions. Sentences (Experiment 1) and random one-, three-, and five-word sequences (Experiment 2) were interrupted using either a primary gating rate alone (0.5-24 Hz) or a combined primary and faster secondary rate. The secondary rate interrupted only speech left intact after primary gating, reducing the original speech to 25%. In both experiments, intelligibility increased with primary rate, but varied with memory load and speech material (highest for sentences, lowest for five-word sequences). With dual-rate gating of sentences, intelligibility with fast secondary rates was superior to that with single rates and a 25% duty cycle, approaching that of single rates with a 50% duty cycle for some low and high rates. For dual-rate gating of words, the positive effect of fast secondary gating was smaller than for sentences, and the advantage of sentences over word sequences was not obtained in many dual-rate conditions. These findings suggest that integration of interrupted speech fragments after gating depends on the duration of the gated speech interval and that sufficiently robust acoustic phonetic word cues are needed to access higher-level contextual sentence information. PMID- 21973364 TI - A cautionary note on the use of the adaptive up-down method. AB - Up-down staircases with equal sizes for the steps up and down are widely used to estimate detection and discrimination thresholds in psychoacoustics, but the conventional average-of-reversals estimator does not converge on its presumed percent point in Yes-No tasks or in two-alternative forced-choice detection tasks. The particular percent point of convergence is partly determined by the relative size of the steps with respect to the spread (inverse of slope) of the underlying psychometric function. In particular, threshold is increasingly underestimated as the spread of the psychometric function decreases. This characteristic may have serious consequences when thresholds estimated via up down staircases are compared across conditions in which the spread of the psychometric function varies, because then these thresholds do not represent comparable measures of performance. This paper documents the misbehavior of the average-of-reversals estimator under up-down rules and types of forced-choice task that are in common use in psychoacoustics but which have not been studied before in simulations. It is also shown that a relatively simple modification of the up-down design (namely, using steps up and down of different size and in a certain ratio depending only on the task and the up-down rule being used) stabilizes the performance of these staircases. PMID- 21973363 TI - Evidence of across-channel processing for spectral-ripple discrimination in cochlear implant listeners. AB - Spectral-ripple discrimination has been used widely for psychoacoustical studies in normal-hearing, hearing-impaired, and cochlear implant listeners. The present study investigated the perceptual mechanism for spectral-ripple discrimination in cochlear implant listeners. The main goal of this study was to determine whether cochlear implant listeners use a local intensity cue or global spectral shape for spectral-ripple discrimination. The effect of electrode separation on spectral ripple discrimination was also evaluated. Results showed that it is highly unlikely that cochlear implant listeners depend on a local intensity cue for spectral-ripple discrimination. A phenomenological model of spectral-ripple discrimination, as an "ideal observer," showed that a perceptual mechanism based on discrimination of a single intensity difference cannot account for performance of cochlear implant listeners. Spectral modulation depth and electrode separation were found to significantly affect spectral-ripple discrimination. The evidence supports the hypothesis that spectral-ripple discrimination involves integrating information from multiple channels. PMID- 21973365 TI - Resonances and wave propagation velocity in the subglottal airways. AB - Previous studies of subglottal resonances have reported findings based on relatively few subjects, and the relations between these resonances, subglottal anatomy, and models of subglottal acoustics are not well understood. In this study, accelerometer signals of subglottal acoustics recorded during sustained [a:] vowels of 50 adult native speakers (25 males, 25 females) of American English were analyzed. The study confirms that a simple uniform tube model of subglottal airways, closed at the glottis and open at the inferior end, is appropriate for describing subglottal resonances. The main findings of the study are (1) whereas the walls may be considered rigid in the frequency range of Sg2 and Sg3, they are yielding and resonant in the frequency range of Sg1, with a resulting ~4/3 increase in wave propagation velocity and, consequently, in the frequency of Sg1; (2) the "acoustic length" of the equivalent uniform tube varies between 18 and 23.5 cm, and is approximately equal to the height of the speaker divided by an empirically determined scaling factor; (3) trachea length can also be predicted by dividing height by another empirically determined scaling factor; and (4) differences between the subglottal resonances of males and females can be accounted for by height-related differences. PMID- 21973366 TI - Control of phonemic length contrast and speech rate in vocalic and consonantal syllable nuclei. AB - This paper investigates the mechanisms controlling the phonemic quantity contrast and speech rate in nonsense p(1)Np(2)a words read by five Slovak speakers in normal and fast speech rate. N represents a syllable nucleus, which in Slovak corresponds to long and short vowels and liquid consonants. The movements of the lips and the tongue were recorded with an electromagnetometry system. Together with the acoustic durations of p(1), N, and p(2), gestural characteristics of three core movements were extracted: p(1) lip opening, tongue movement for (N)ucleus, and p(2) lip closing. The results show that, although consonantal and vocalic nuclei are predictably different on many kinematic measures, their common phonological behavior as syllabic nuclei may be linked to a stable temporal coordination of the consonantal gestures flanking the nucleus. The functional contrast between phonemic duration and speech rate was reflected in the bias in the control mechanisms they employed: the strategies robustly used for signaling phonemic duration, such as the degree of coproduction of the two lip movements, showed a minimal effect of speech rate, while measures greatly affected by speech rate, such as p(2) acoustic duration, or the degree of p(1)-N gestural coproduction, tended to be minimally influenced by phonemic quantity. PMID- 21973367 TI - Experimental validation of flow models for a rigid vocal tract replica. AB - Flow through the vocal tract is studied through an in vitro rigid replica for different geometrical configurations and steady flow conditions with bulk Reynolds numbers Re<15,000. The vocal tract geometry is approximated by two consecutive obstacles, representing "tongue" and "tooth," in a rectangular channel of fixed length. For the upstream tongue obstacle with fixed constriction degree (81%) the streamwise position is varied and for the downstream obstacle the constriction degree is varied from 0% up to 96%. Different upstream pressures are considered for each geometrical configuration. Point pressure measurements at three fixed locations along the channel are experimentally assessed. In addition, the volume airflow rate is measured. The pressure distribution is estimated with a one-dimensional flow model, and the effects of different corrections to a laminar irrotational flow are assessed. The model outcome is validated against experimental data. Depending on the geometrical configuration, the best model accuracy is obtained by accounting for viscosity (needed for constriction degrees at the tooth that are small, i.e.,<=58%, or very large, i.e., >=96%), a sudden constriction (large gap between both constrictions), or a bending geometry (narrow gap between both constrictions). Best overall model errors vary between 4% and 30% for all assessed geometrical configurations in cases where a tongue obstacle is present. PMID- 21973368 TI - Acoustic-phonetic characteristics of speech produced with communicative intent to counter adverse listening conditions. AB - This study investigated whether speech produced in spontaneous interactions when addressing a talker experiencing actual challenging conditions differs in acoustic-phonetic characteristics from speech produced (a) with communicative intent under more ideal conditions and (b) without communicative intent under imaginary challenging conditions (read, clear speech). It also investigated whether acoustic-phonetic modifications made to counteract the effects of a challenging listening condition are tailored to the condition under which communication occurs. Forty talkers were recorded in pairs while engaged in "spot the difference" picture tasks in good and challenging conditions. In the challenging conditions, one talker heard the other (1) via a three-channel noise vocoder (VOC); (2) with simultaneous babble noise (BABBLE). Read, clear speech showed more extreme changes in median F0, F0 range, and speaking rate than speech produced to counter the effects of a challenging listening condition. In the VOC condition, where F0 and intensity enhancements are unlikely to aid intelligibility, talkers did not change their F0 median and range; mean energy and vowel F1 increased less than in the BABBLE condition. This suggests that speech production is listener-focused, and that talkers modulate their speech according to their interlocutors' needs, even when not directly experiencing the challenging listening condition. PMID- 21973369 TI - Intelligibility of reverberant noisy speech with ideal binary masking. AB - For a mixture of target speech and noise in anechoic conditions, the ideal binary mask is defined as follows: It selects the time-frequency units where target energy exceeds noise energy by a certain local threshold and cancels the other units. In this study, the definition of the ideal binary mask is extended to reverberant conditions. Given the division between early and late reflections in terms of speech intelligibility, three ideal binary masks can be defined: an ideal binary mask that uses the direct path of the target as the desired signal, an ideal binary mask that uses the direct path and early reflections of the target as the desired signal, and an ideal binary mask that uses the reverberant target as the desired signal. The effects of these ideal binary mask definitions on speech intelligibility are compared across two types of interference: speech shaped noise and concurrent female speech. As suggested by psychoacoustical studies, the ideal binary mask based on the direct path and early reflections of target speech outperforms the other masks as reverberation time increases and produces substantial reductions in terms of speech reception threshold for normal hearing listeners. PMID- 21973370 TI - The dynamic range of useful temporal fine structure cues for speech in the presence of a competing talker. AB - Within an auditory channel, the speech waveform contains both temporal envelope (E(O)) and temporal fine structure (TFS) information. Vocoder processing extracts a modified version of the temporal envelope (E') within each channel and uses it to modulate a channel carrier. The resulting signal, E'(Carr), has reduced information content compared to the original "E(O) + TFS" signal. The dynamic range over which listeners make additional use of E(O) + TFS over E'(Carr) cues was investigated in a competing-speech task. The target-and-background mixture was processed using a 30-channel vocoder. In each channel, E(O) + TFS replaced E'(Carr) at either the peaks or the valleys of the signal. The replacement decision was based on comparing the short-term channel level to a parametrically varied "switching threshold," expressed relative to the long-term channel level. Intelligibility was measured as a function of switching threshold, carrier type, target-to-background ratio, and replacement method. Scores showed a dependence on all four parameters. Derived intensity-importance functions (IIFs) showed that E(O) + TFS information from 8-13 dB below to 10 dB above the channel long-term level was important. When E(O) + TFS information was added at the peaks, IIFs peaked around -2 dB, but when E(O) + TFS information was added at the valleys, the peaks lay around +1 dB. PMID- 21973371 TI - Estimating speech spectra for copy synthesis by linear prediction and by hand. AB - Linear prediction is a widely available technique for analyzing acoustic properties of speech, although this method is known to be error-prone. New tests assessed the adequacy of linear prediction estimates by using this method to derive synthesis parameters and testing the intelligibility of the synthetic speech that results. Matched sets of sine-wave sentences were created, one set using uncorrected linear prediction estimates of natural sentences, the other using estimates made by hand. Phoneme restrictions imposed on linguistic properties allowed comparisons between continuous and intermittent voicing, oral or nasal and fricative manner, and unrestricted phonemic variation. Intelligibility tests revealed uniformly good performance with sentences created by hand-estimation and a minimal decrease in intelligibility with estimation by linear prediction due to manner variation with continuous voicing. Poorer performance was observed when linear prediction estimates were used to produce synthetic versions of phonemically unrestricted sentences, but no similar decline was observed with synthetic sentences produced by hand estimation. The results show a substantial intelligibility cost of reliance on uncorrected linear prediction estimates when phonemic variation approaches natural incidence. PMID- 21973372 TI - Ear and pitch segregation in Deutsch's octave illusion persist following switch from stimulus alternation to repetition. AB - Deutsch's octave illusion occurs when two tones that are spaced an octave apart are repeatedly presented in alternation; the sequence is presented to both ears simultaneously but offset by one tone, so that two dichotic chords are repeatedly presented in alternation. The most common illusory percept consists of an intermittent high tone in one ear alternating with an intermittent low tone in the other ear. The aim of this study was to investigate whether, once the illusory percept has emerged, the illusion will persist when the original sequence is followed by another sequence consisting of the repeated presentation of one of the two dichotic chords. Forty naive subjects were tested with stimuli consisting first of a priming sequence containing dichotic octaves alternating between ears followed immediately by a test sequence consisting of a single dichotic octave presented repeatedly. The durations of the priming and test sequences were manipulated. The findings showed that the illusory percept is maintained after the switch from alternation to repetition and that the relative length of the priming and test sequences has a negligible influence on the persistence of the illusory percept. PMID- 21973373 TI - Modal parameters of two incomplete and complete guitars differing in the bracing pattern of the soundboard. AB - Similarities and differences in vibrational behavior of two guitars having a symmetric Torres bracing pattern and an asymmetric pattern forming a lattice on a soundboard are investigated by means of the modal analysis technique and laser Doppler vibrometry (LDV) measurements. Instruments are investigated before and after a bridge and strings assembling (i.e., they are incomplete or complete). The bracing pattern and the absence/presence of the bridge and strings have some effect on modal frequencies and mode shapes. The bracing pattern does not affect the sequence of at least first three low frequency mode shapes of incomplete/complete instruments but affects their modal frequencies. Depending on frequency, the bridge behaves either as a rigid or a flexible structure. PMID- 21973374 TI - A causal and fractional all-frequency wave equation for lossy media. AB - This work presents a lossy partial differential acoustic wave equation including fractional derivative terms. It is derived from first principles of physics (mass and momentum conservation) and an equation of state given by the fractional Zener stress-strain constitutive relation. For a derivative order alpha in the fractional Zener relation, the resulting absorption alpha(k) obeys frequency power-laws as alpha(k) ? omega(1+alpha) in a low-frequency regime, alpha(k) ? omega(1-alpha/2) in an intermediate-frequency regime, and alpha(k) ? omega(1 alpha) in a high-frequency regime. The value alpha=1 corresponds to the case of a single relaxation process. The wave equation is causal for all frequencies. In addition the sound speed does not diverge as the frequency approaches infinity. This is an improvement over a previously published wave equation building on the fractional Kelvin-Voigt constitutive relation. PMID- 21973375 TI - Temperature dependent ultrasonic characterization of biological media. AB - Quantitative ultrasound (QUS) is an imaging technique that can be used to quantify tissue microstructure giving rise to scattered ultrasound. Other ultrasonic properties, e.g., sound speed and attenuation, of tissues have been estimated versus temperature elevation and found to have a dependence with temperature. Therefore, it is hypothesized that QUS parameters may be sensitive to changes in tissue microstructure due to temperature elevation. Ultrasonic backscatter experiments were performed on tissue-mimicking phantoms and freshly excised rabbit and beef liver samples. The phantoms were made of agar and contained either mouse mammary carcinoma cells (4T1) or chinese hamster ovary cells (CHO) as scatterers. All scatterers were uniformly distributed spatially at random throughout the phantoms. All the samples were scanned using a 20-MHz single-element f/3 transducer. Quantitative ultrasound parameters were estimated from the samples versus increases in temperature from 37 degrees C to 50 degrees C in 1 degrees C increments. Two QUS parameters were estimated from the backscatter coefficient [effective scatterer diameter (ESD) and effective acoustic concentration (EAC)] using a spherical Gaussian scattering model. Significant increases in ESD and decreases in EAC of 20%-40% were observed in the samples over the range of temperatures examined. The results of this study indicate that QUS parameters are sensitive to changes in temperature. PMID- 21973376 TI - Automated extraction of odontocete whistle contours. AB - Many odontocetes produce frequency modulated tonal calls known as whistles. The ability to automatically determine time * frequency tracks corresponding to these vocalizations has numerous applications including species description, identification, and density estimation. This work develops and compares two algorithms on a common corpus of nearly one hour of data collected in the Southern California Bight and at Palmyra Atoll. The corpus contains over 3000 whistles from bottlenose dolphins, long- and short-beaked common dolphins, spinner dolphins, and melon-headed whales that have been annotated by a human, and released to the Moby Sound archive. Both algorithms use a common signal processing front end to determine time * frequency peaks from a spectrogram. In the first method, a particle filter performs Bayesian filtering, estimating the contour from the noisy spectral peaks. The second method uses an adaptive polynomial prediction to connect peaks into a graph, merging graphs when they cross. Whistle contours are extracted from graphs using information from both sides of crossings. The particle filter was able to retrieve 71.5% (recall) of the human annotated tonals with 60.8% of the detections being valid (precision). The graph algorithm's recall rate was 80.0% with a precision of 76.9%. PMID- 21973377 TI - Statistics of the envelope of ultrasonic backscatter from human trabecular bone. AB - The paper describes the investigations intended to compare the results of experimental measurements of backscattering properties of the trabecular bone with the results of computer simulations. Ultrasonic RF echoes were collected using two bone scanners operating at 0.58 and 1.3 MHz. The simulations of the backscattered RF echoes were performed using the scattering model of the trabecular bone that consisted of cylindrical and spherical elements uniformly distributed in water-like medium. For each measured or simulated RF backscatter the statistical properties of the signal envelope were determined. Experimental results suggest deviations of the backscattering properties from the Rayleigh distribution. The results of simulation suggest that deviation from Rayleigh distribution depends on the variation of trabeculae diameters and the number of thin trabeculae. Experimentally determined deviations corresponded well to the deviations calculated from simulated echoes assuming trabeculae thickness variation equaled to the earlier published histomorphometric study results. PMID- 21973378 TI - Determining attenuation properties of interfering fast and slow ultrasonic waves in cancellous bone. AB - Previous studies have shown that interference between fast waves and slow waves can lead to observed negative dispersion in cancellous bone. In this study, the effects of overlapping fast and slow waves on measurements of the apparent attenuation as a function of propagation distance are investigated along with methods of analysis used to determine the attenuation properties. Two methods are applied to simulated data that were generated based on experimentally acquired signals taken from a bovine specimen. The first method uses a time-domain approach that was dictated by constraints imposed by the partial overlap of fast and slow waves. The second method uses a frequency-domain log-spectral subtraction technique on the separated fast and slow waves. Applying the time domain analysis to the broadband data yields apparent attenuation behavior that is larger in the early stages of propagation and decreases as the wave travels deeper. In contrast, performing frequency-domain analysis on the separated fast waves and slow waves results in attenuation coefficients that are independent of propagation distance. Results suggest that features arising from the analysis of overlapping two-mode data may represent an alternate explanation for the previously reported apparent dependence on propagation distance of the attenuation coefficient of cancellous bone. PMID- 21973380 TI - Development of a contact call in black-capped chickadees (Poecile atricapillus) hand-reared in different acoustic environments. AB - The tseet contact call, common to black-capped (Poecile atricapillus) and mountain chickadees (P. gambeli), is the most frequently produced vocalization of each species. Previous work has characterized the tseet call of black-capped and mountain chickadees from different geographic locations in terms of nine acoustic features. In the current study, using similar methods, the tseet call of black capped chickadees that were hand reared with either conspecifics, heterospecifics (mountain chickadees), or in isolation from adult chickadees are described. Analysis of call features examined which acoustic features were most affected by rearing environment, and revealed that starting frequency and the slope of the descending portion of the tseet call differed between black-capped chickadees reared with either conspecific or heterospecific adults. Birds reared in isolation from adults differed from the other hand-reared groups on almost every acoustic feature. Chickadee tseet calls are more individualized when they are reared with adult conspecifics or heterospecifics compared to chickadees that are reared in isolation from adults. The current results suggest a role of learning in this commonly used contact call. PMID- 21973379 TI - Estimation of mechanical properties of a viscoelastic medium using a laser induced microbubble interrogated by an acoustic radiation force. AB - An approach to assess the mechanical properties of a viscoelastic medium using laser-induced microbubbles is presented. To measure mechanical properties of the medium, dynamics of a laser-induced cavitation microbubble in viscoelastic medium under acoustic radiation force was investigated. An objective lens with a 1.13 numerical aperture and an 8.0 mm working distance was designed to focus a 532 nm wavelength nanosecond pulsed laser beam and to create a microbubble at the desired location. A 3.5 MHz ultrasound transducer was used to generate acoustic radiation force to excite a laser-induced microbubble. Motion of the microbubble was tracked using a 25 MHz imaging transducer. Agreement between a theoretical model of bubble motion in a viscoelastic medium and experimental measurements was demonstrated. Young's modulii reconstructed using the laser-induced microbubble approach were compared with those measured using a direct uniaxial method over the range from 0.8 to 13 kPa. The results indicate good agreement between methods. Thus, the proposed approach can be used to assess the mechanical properties of a viscoelastic medium. PMID- 21973381 TI - Evidence for simultaneous sound production in the bowhead whale (Balaena mysticetus). AB - Simultaneous production of two harmonically independent sounds, the two-voice phenomenon, is a well-known feature in bird song. Some toothed whales can click and whistle simultaneously, and a few studies have also reported simultaneous sound production by baleen whales. The mechanism for sound production in toothed whales has been largely uncovered within the last three decades, whereas mechanism for sound production in baleen whales remains poorly understood. This study provides three lines of evidence from recordings made in 2008 and 2009 in Disko Bay, Western Greenland, strongly indicating that bowhead whales are capable of simultaneous dual frequency sound production. This capability may function to enable more complex singing in an acoustically mediated reproductive advertisement display, as has been suggested for songbirds, and/or have significance in individual recognition. PMID- 21973382 TI - Source parameters of echolocation clicks from wild bottlenose dolphins (Tursiops aduncus and Tursiops truncatus). AB - The Indian Ocean and Atlantic bottlenose dolphins (Tursiops aduncus and Tursiops truncatus) are among the best studied echolocating toothed whales. However, almost all echolocation studies on bottlenose dolphins have been made with captive animals, and the echolocation signals of free-ranging animals have not been quantified. Here, biosonar source parameters from wild T. aduncus and T. truncatus were measured with linear three- and four-hydrophone arrays in four geographic locations. The two species had similar source parameters, with source levels of 177-228 dB re 1 MUPa peak to peak, click durations of 8-72 MUs, centroid frequencies of 33-109 kHz and rms bandwidths between 23 and 54 kHz. T. aduncus clicks had a higher frequency emphasis than T. truncatus. The transmission directionality index was up to 3 dB higher for T. aduncus (29 dB) as compared to T. truncatus (26 dB). The high directionality of T. aduncus does not appear to be only a physical consequence of a higher frequency emphasis in clicks, but may also be caused by differences in the internal properties of the sound production system. PMID- 21973383 TI - Tonal vocalizations in the red wolf (Canis rufus): potential functions of nonlinear sound production. AB - The purpose of this study is to further understanding of the function of nonlinear vocalizations in red wolves (Canis rufus) by examining the acoustic, structural, and contextual characteristics of nonlinear sounds as compared to linear sounds. Video recordings of captive wolves from a breeding facility were analyzed. The acoustic nature of sound units was consistent with that of other social canids. The sound units included high-frequency squeaks (2600-9500 Hz) and low-frequency wuhs (160-1600 Hz) occurring either as separate units or in combination as nonlinear units (squeak-wuh frequency jumps, biphonations, squeaks with sidebands) and frequency jumps within squeaks. These low-amplitude sounds occurred in trains of 1-30 units that were classified as squeak vocalizations (49%), wuh vocalizations (19%), and nonlinear vocalizations (any combination including one or more nonlinear units, 32%). Nonlinear vocalizations transitioned directionally from high-frequency units to mixed-frequency units which has implications for the study of sound production and function. Wolves squeaked most often when oriented toward others, implying a solicitation function, while wuh vocalizations were more common during social interactions. Nonlinear vocalizations occurred most often during penmate-play or when oriented toward neighbors, indicating that nonlinear sound production may signal an increase in arousal. PMID- 21973384 TI - Passive acoustic survey of Yangtze finless porpoises using a cargo ship as a moving platform. AB - In order to periodically investigate the population and distribution of the Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis) in its main distribution range in the Yangtze River, a passive acoustic system deployed on a cargo ship as a moving platform, rather than a dedicated research ship, was developed. A stereo acoustic event data-logger (A-tag) was installed on the cargo ship to passively detect phonating animals. In three surveys carried out in the Yangtze River from Wuhan to Shanghai, an average of 6059 clicks in each survey and 284 porpoises in total were acoustically detected along an 1100-km stretch. The animals were detected frequently in most of the survey range except two "gap sections" with 40 and 60 km lengths, respectively, where no animals were detected in all three surveys. Detected group sizes of the animals in each 120-s time window were not significantly different among the surveys, but the distribution pattern was different and suggested seasonal migration. The cargo ship based passive acoustic survey was effective in detecting phonating animals and can potentially monitor the distribution and population trend over time. Compared to surveys that used dedicated research ships, the present method is more cost effective. PMID- 21973385 TI - Lateralization of acoustic signals by dichotically listening budgerigars (Melopsittacus undulatus). AB - Sound localization allows humans and animals to determine the direction of objects to seek or avoid and indicates the appropriate position to direct visual attention. Interaural time differences (ITDs) and interaural level differences (ILDs) are two primary cues that humans use to localize or lateralize sound sources. There is limited information about behavioral cue sensitivity in animals, especially animals with poor sound localization acuity and small heads, like budgerigars. ITD and ILD thresholds were measured behaviorally in dichotically listening budgerigars equipped with headphones in an identification task. Budgerigars were less sensitive than humans and cats, and more similar to rabbits, barn owls, and monkeys, in their abilities to lateralize dichotic signals. Threshold ITDs were relatively constant for pure tones below 4 kHz, and were immeasurable at higher frequencies. Threshold ILDs were relatively constant over a wide range of frequencies, similar to humans. Thresholds in both experiments were best for broadband noise stimuli. These lateralization results are generally consistent with the free field localization abilities of these birds, and add support to the idea that budgerigars may be able to enhance their cues to directional hearing (e.g., via connected interaural pathways) beyond what would be expected based on head size. PMID- 21974481 TI - A note about insensitivity to pitch-change direction. AB - Some listeners are insensitive to the direction of pure-tone frequency changes when the standard frequency is roved widely over trials, but less so when the standard frequency is fixed and trial-by-trial feedback is provided. The present experiment tested the hypothesis that fixing the standard frequency and providing feedback is advantageous for direction-impaired listeners because under these conditions the listeners can learn to respond correctly without genuinely perceiving frequency-change direction. This hypothesis was ruled out by the experiment. It appears instead that direction-impaired listeners find it difficult to ignore the irrelevant frequency changes introduced by roving. PMID- 21974482 TI - Scattering of a spherical wave by a small sphere: an elementary solution. AB - Wave scattering by objects that are small compared to the wavelength (Rayleigh scattering) is usually studied for plane incident waves. However, knowledge of the full Green's function of the problem becomes necessary when the separation of scatterers from either an interface or each other is comparable to the scatterers' dimensions. Here, an elementary analytic solution is derived for diffraction of a spherical sound wave by a small, soft sphere. The approximate solution is obtained from asymptotic expansions of an exact solution, holds everywhere outside the sphere, and reduces to classical results due to Kelvin and Rayleigh in appropriate special cases. PMID- 21974483 TI - Modification of digital music files for use in human temporary threshold shift studies. AB - An exposure that is reproducible across clinical/laboratory environments, and appealing to subjects, is described here. Digital music files are level-equated within and across songs such that playlists deliver an exposure that is consistent across time. Modified music is more pleasant to listen to than pure tones or shaped noise, and closely follows music exposures subjects may normally experience. Multiple therapeutics reduce noise-induced hearing loss in animals but human trial design is complicated by limited access to noise-exposed subject populations. The development of standard music exposure parameters for temporary threshold shift studies would allow comparison of protection across agents with real-world relevant stimuli in human subjects. PMID- 21974484 TI - Developmental changes in ultrasonic vocalizations by infant Japanese echolocating bats, Pipistrellus abramus. AB - Developmental changes in vocalizations by Pipistrellus abramus were investigated during the first post-natal month. Vocalizations by pups on the day of birth were frequency-modulated ultrasounds from 30.0 +/- 4.0 kHz to 19.3 +/- 1.9 kHz with multiple harmonics. The terminal frequency of the second harmonic (TF(2)) of pup vocalizations corresponded to that of the fundamental (TF(1)) in adult bats (41.4 +/- 2.6 kHz), suggesting that pup vocalizations can be easily detected by the mother. In addition, there are two types of infant vocalization: short duration echolocation precursor and long duration isolation calls, which showed separate developmental patterns over time. PMID- 21974485 TI - Range aliasing in frequency coherent geoacoustic inversion. AB - This paper discusses the effects of frequency selection on source localization and geoacoustic inversion methods that use frequency coherent objective functions. Matched-field processors based on frequency-coherent objective functions often have rapidly fluctuating range ambiguity surfaces. Insufficient sampling in frequency domain results in range aliasing terms that affect geoacoustic inversion. Range aliasing and its effects on source localization and environmental parameter inversion are demonstrated on data collected during the MAPEX2000 experiment. Guidance for frequency selection to avoid range aliasing is provided. PMID- 21974486 TI - Time reversal communication in a time-varying sparse channel. AB - Recently time reversal (TR) communications has been extended to time-varying channels. The basic idea is to implement it on a block-by-block basis such that within each block the channel remains time-invariant and subsequently is updated using detected symbols (decision-directed mode). Using experimental data (12-20 kHz) collected in shallow water, this letter investigates three different block based TR approaches: (1) without explicit phase tracking, (2) with phase tracking, and (3) exploiting channel sparsity. The TR approaches then are compared to a conventional adaptive multichannel equalizer. It is found that approach (3) generally provides the best performance and robustness. PMID- 21974487 TI - Use of parabolic reflector to amplify in-air signals generated during impact-echo testing. AB - The impact-echo method is a commonly used nondestructive testing technique for elastic plates in civil engineering. The impact-echo mode corresponds to the frequency at zero group velocity of S(1) Lamb mode. Recent development of the air coupled impact-echo (ACIE) method introduces the possibility for rapid scanning of large structures and increases the practicality of in situ measurements. However, sensors used in ACIE are susceptible to ambient noise, which complicates in situ ACIE measurements. This letter presents the results of ACIE measurements taken using a parabolic reflector together with standard measurement microphones to increase the signal to noise ratio for ACIE measurements. The signal gain and effects of sensor location with respect to impact location are discussed. PMID- 21974488 TI - Noise interferometry in an inhomogeneous environment in the geometric limit. AB - An approximation to the transient Green's function G(x(a)?x(b),t) between points x(a) and x(b) can be estimated by taking the time derivative of the correlation function C(ab)(t) of records of ambient noise measured at locations x(a) and x(b). From the general relationship between C(ab)(t) and G(x(a)?x(b),t) it is shown, using a stationary-phase-like argument, that in an inhomogeneous environment in the geometric limit C(ab)(t) consists of a superposition of signed step functions and two-sided logarithmic singularities that are delayed in time by the travel times of the rays connecting x(a) and x(b). PMID- 21974489 TI - Accounting for the stability of microbubbles to multi-pulse excitation using a lipid-shedding model. AB - Interest in microbubble ultrasound contrast agents as therapeutic and quantitative imaging tools has increased the need for accurate modeling of their behavior. Experiments have shown that some bubbles shrink significantly over the course of a single pulse but that the bubbles may eventually reach a stable size after many insonations. Here, it is shown from dimensional arguments that diffusion phenomena are negligible on the time scales that characterize a typical ultrasound pulse. Subsequently, a new model describing both a lipid-shedding mechanism and a nonlinear surface viscosity is developed and shown to provide a more accurate description of the observed experimental behavior. PMID- 21974490 TI - Native dialect matters: perceptual assimilation of Dutch vowels by Czech listeners. AB - Naive listeners' perceptual assimilations of non-native vowels to first-language (L1) categories can predict difficulties in the acquisition of second-language vowel systems. This study demonstrates that listeners having two slightly different dialects as their L1s can differ in the perception of foreign vowels. Specifically, the study shows that Bohemian Czech and Moravian Czech listeners assimilate Dutch high front vowels differently to L1 categories. Consequently, the listeners are predicted to follow different paths in acquiring these Dutch vowels. These findings underscore the importance of carefully considering the specific dialect background of participants in foreign- and second-language speech perception studies. PMID- 21974491 TI - Influence of pitch, loudness, and timbre on the perception of instrument dynamics. AB - The effect of variations in pitch, loudness, and timbre on the perception of the dynamics of isolated instrumental tones is investigated. A full factorial design was used in a listening experiment. The subjects were asked to indicate the perceived dynamics of each stimulus on a scale from pianissimo to fortissimo. Statistical analysis showed that for the instruments included (i.e., clarinet, flute, piano, trumpet, and violin) timbre and loudness had equally large effects, while pitch was relevant mostly for the first three. The results confirmed our hypothesis that loudness alone is not a reliable estimate of the dynamics of musical tones. PMID- 21974492 TI - Stochastic channel simulator based on local scattering functions. AB - This letter addresses the limitations of the stochastic channel simulation approach employed in wireless channels when directly applied to underwater channels. First it is shown analytically why the simulation method fails when the correlated taps each have a different Doppler spectrum. Then, based on the idea of local scattering functions, we propose a simple solution to the problem of simulating a channel with correlated taps where the correlated taps occur in subgroups with each of the subgroups having a different Doppler spectrum, applicable to underwater channels. Our simulation approach is tested successfully on the KAM08 channel. PMID- 21974493 TI - Enhanced bimodal distributions facilitate the learning of second language vowels. AB - This study addresses the questions of whether listening to a bimodal distribution of vowels improves adult learners' categorization of a difficult L2 vowel contrast and whether enhancing the acoustic differences between the vowels in the distribution yields better categorization performance. Spanish learners of Dutch were trained on a natural bimodal or an enhanced bimodal distribution of the Dutch vowels /alpha/ and /a?/, with the average productions of the vowels or more extreme values as the endpoints respectively. Categorization improved for learners who listened to the enhanced distribution, which suggests that adults profit from input with properties similar to infant-directed speech. PMID- 21974494 TI - Nonlinear optoacoustic transformation in the system of dielectric substrate/submicron metal coating/liquid. AB - The optoacoustic method has been shown to be an accurate technique for the measurement of the properties of submicron metal coatings deposited on a dielectric substrate, i.e., mirrors. The method has been previously theoretically described in terms of a linear model of optoacoustic transformation in a system substrate/coating/liquid. The goal of the present work was to determine the limits at which the linear model is still applicable. The modification of the laser induced acoustic signal profiles and transfer functions of optoacoustic transformation versus the laser fluence was studied for two liquids: ethanol and water. PMID- 21974495 TI - Time reversal reconstruction of finite sized sources in elastic media. AB - The ability of the time reversal process to reconstruct sources of finite size relative to a wavelength is investigated. Specifically the quality of the spatial reconstruction of a finite sized source will be presented through the use of time reversal experiments conducted on an aluminum plate. The data presented in the paper show that time reversal can reconstruct a source equally well regarding less of its size, when the source is a half wavelength or less in size. The quality of spatial reconstruction when the source is larger than a half wavelength progressively decreases with the size of the source. PMID- 21974496 TI - Cross-language perceptual similarity predicts categorial discrimination of American vowels by naive Japanese listeners. AB - Current speech perception models propose that relative perceptual difficulties with non-native segmental contrasts can be predicted from cross-language phonetic similarities. Japanese (J) listeners performed a categorical discrimination task in which nine contrasts (six adjacent height pairs, three front/back pairs) involving eight American (AE) vowels [i?, i, epsilon, ae?, alpha?, v, upsilon, u?] in /hVbe/ disyllables were tested. The listeners also completed a perceptual assimilation task (categorization as J vowels with category goodness ratings). Perceptual assimilation patterns (quantified as categorization overlap scores) were highly predictive of discrimination accuracy (r(s)=0.93). Results suggested that J listeners used both spectral and temporal information in discriminating vowel contrasts. PMID- 21974497 TI - Beamforming using compressive sensing. AB - Compressive sensing (CS) is compared with conventional beamforming using horizontal beamforming of at-sea, towed-array data. They are compared qualitatively using bearing time records and quantitatively using signal-to interference ratio. Qualitatively, CS exhibits lower levels of background interference than conventional beamforming. Furthermore, bearing time records show increasing, but tolerable, levels of background interference when the number of elements is decreased. For the full array, CS generates signal-to-interference ratio of 12 dB, but conventional beamforming only 8 dB. The superiority of CS over conventional beamforming is much more pronounced with undersampling. PMID- 21974498 TI - Calibration of otoacoustic emission probe microphones. AB - Recently, investigators of otoacoustic emissions (OAEs) have shown interest in measuring OAEs to frequencies higher than 10 kHz. Most commercial instruments used to measure OAEs do not specify the microphone frequency response at higher frequencies, nor does their typically integrated design make it convenient to measure it. OAE probes manufactured by Etymotic Research have reasonably constant microphone sensitivity up to about 10 kHz and allow direct access to both the sound sources and microphone preamplifier output. A detailed procedure for calibrating the Etymotic Research OAE probe microphone to extend its usable frequency range to frequencies up to 20 kHz is described. PMID- 21974499 TI - The effects of non-cardioid directivity on incidence angle estimation using the polar energy time curve. AB - Assessment of desirable reflections and control of undesirable reflections in rooms are best accomplished if the reflecting surfaces are properly localized. Several measurement techniques exist to identify the incident direction of reflected sound, including the useful polar energy time curve (Polar ETC), which requires six cardioid impulse response measurements along the Cartesian axes. The purpose of this investigation is to quantify the incidence angle estimation error introduced into the Polar ETC by non-cardioid microphone directivities. The results demonstrate that errors may be minimized with a cardioid-family microphone possessing a certain range of directivities and by maximizing the measurement signal-to-noise ratio. PMID- 21974500 TI - Automatic speech recognition using articulatory features from subject-independent acoustic-to-articulatory inversion. AB - An automatic speech recognition approach is presented which uses articulatory features estimated by a subject-independent acoustic-to-articulatory inversion. The inversion allows estimation of articulatory features from any talker's speech acoustics using only an exemplary subject's articulatory-to-acoustic map. Results are reported on a broad class phonetic classification experiment on speech from English talkers using data from three distinct English talkers as exemplars for inversion. Results indicate that the inclusion of the articulatory information improves classification accuracy but the improvement is more significant when the speaking style of the exemplar and the talker are matched compared to when they are mismatched. PMID- 21974501 TI - Probing the interior of a solid volume with time reversal and nonlinear elastic wave spectroscopy. AB - A nonlinear scatterer is simulated in the body of a sample and demonstrates a technique to locate and define the elastic nature of the scatterer. Using the principle of time reversal, elastic wave energy is focused at the interface between blocks of optical grade glass and aluminum. Focusing of energy at the interface creates nonlinear wave scattering that can be detected on the sample perimeter with time-reversal mirror elements. The nonlinearly generated scattered signal is bandpass filtered about the nonlinearly generated components, time reversed and broadcast from the same mirror elements, and the signal is focused at the scattering location on the interface. PMID- 21974502 TI - Effects of roving level and spectral range on vowel formant discrimination. AB - Thresholds of vowel formant discrimination for F1 and F2 of isolated vowels with full and partial vowel spectra were measured for normal-hearing listeners at fixed and roving speech levels. Performance of formant discrimination was significantly better for fixed levels than for roving levels with both full and partial spectra. The effect of vowel spectral range was present only for roving levels, but not for fixed levels. These results, consistent with studies of profile analysis, indicated different perceptual mechanisms for listeners to discriminate vowel formant frequency at fixed and roving levels. PMID- 21974503 TI - Separation of zeros for source signature identification under reverberant path conditions. AB - This paper presents an approach to distinguishing the zeros representing a sound source from those representing the transfer function on the basis of Lyon's residue-sign model. In machinery noise diagnostics, the source signature must be separated from observation records under reverberant path conditions. In numerical examples and an experimental piano-string vibration analysis, the modal responses could be synthesized by using clustered line-spectrum modeling. The modeling error represented the source signature subject to the source characteristics being given by a finite impulse response. The modeling error can be interpreted as a remainder function necessary for the zeros representing the source signature. PMID- 21974504 TI - Communication: strong excitonic and vibronic effects determine the optical properties of Li2O2. AB - The band structure and optical absorption spectrum of lithium peroxide (Li(2)O(2)) is calculated from first-principles using the G(0)W(0) approximation and the Bethe-Salpeter equation, respectively. A strongly localized (Frenkel type) exciton corresponding to the pi(*)->sigma(*) transition on the O(2)(-2) peroxide ion gives rise to a narrow absorption peak around 1.2 eV below the calculated bandgap of 4.8 eV. In the excited state, the internal O(2)(-2) bond is significantly weakened due to the population of the sigma(*) orbital. As a consequence, the bond is elongated by almost 0.5 A leading to an extreme Stokes shift of 2.6 eV. The strong vibronic coupling entails significant broadening of the excitonic absorption peak in good agreement with diffuse reflectance data on Li(2)O(2) which shows a rather featureless spectrum with an absorption onset around 3.0 eV. These results should be important for understanding the origin of the high potential losses and low current densities, which are presently limiting the performance of Li-air batteries. PMID- 21974506 TI - Mayer-sampling Monte Carlo calculations of uniquely flexible contributions to virial coefficients. AB - We present methods for computing contributions to the virial coefficients uniquely associated with molecular flexibility, and we demonstrate their use with application to the third, fourth, and fifth virial coefficients of united-atom models of linear alkanes and methanol belonging to the suite of transferrable potentials for phase equilibria (TraPPE-UA). We find that these uniquely flexible contributions are more difficult to compute than the remainder of the coefficient, especially for the conditions at which they appear to be most important. The significance of these contributions relative to the full virial coefficient grows with the number of sites (the size of the molecule), the number of molecules, and, to a certain extent, the temperature. The nature of the site site interactions is of great importance: the significance of the uniquely flexible contribution at third and fourth order is orders of magnitude larger for TraPPE-UA methanol, which has Coulombic interactions, than for TraPPE-UA propane, which does not, even though both models have three sites per molecule and comparable bending potentials. While the uniquely flexible contribution of TraPPE UA propane has a negligible impact on its third-order virial-equation-of-state estimate of the critical point, the uniquely flexible contribution of TraPPE-UA methanol increases this estimate of its critical pressure by about 5%. PMID- 21974505 TI - Communication: drift velocity of Brownian particle in a periodically tapered tube induced by a time-periodic force with zero mean: dependence on the force period. AB - We study the drift of a Brownian particle in a periodically tapered tube, induced by a longitudinal time-periodic force of amplitude ?F? that alternates in sign every half-period. The focus is on the velocity dependence on the force period, which is usually considered not tractable analytically. For large ?F? we derive an analytical solution that gives the velocity as a function of the amplitude and the period of the force as well as the geometric parameters of the tube. The solution shows how the velocity decreases from its maximum value to zero as the force period decreases from infinity (adiabatic regime) to zero. Our analytical results are in excellent agreement with those obtained from 3D Brownian dynamics simulations. PMID- 21974507 TI - Hierarchical expansion of the kinetic energy operator in curvilinear coordinates for the vibrational self-consistent field method. AB - A new hierarchical expansion of the kinetic energy operator in curvilinear coordinates is presented and modified vibrational self-consistent field (VSCF) equations are derived including all kinematic effects within the mean field approximation. The new concept for the kinetic energy operator is based on many body expansions for all G matrix elements and its determinant. As a test application VSCF computations were performed on the H(2)O(2) molecule using an analytic potential (PCPSDE) and different hierarchical approximations for the kinetic energy operator. The results indicate that coordinate-dependent reduced masses account for the largest part of the kinetic energy. Neither kinematic couplings nor derivatives of the G matrix nor its determinant had significant effects on the VSCF energies. Only the zero-point value of the pseudopotential yields an offset to absolute energies which, however, is irrelevant for spectroscopic problems. PMID- 21974508 TI - A generalized mean field theory of coarse-graining. AB - A general mean field theory is presented for the construction of equilibrium coarse-grained models. Inverse methods that reconstruct microscopic models from low resolution experimental data can be derived as particular implementations of this theory. The theory also applies to the opposite problem of reduction, where relevant information is extracted from available equilibrium ensemble data. Additionally, a complementary approach is presented and problems of representability in coarse-grained modeling analyzed using information theoretic arguments. These problems are central to the construction of coarse-grained representations of complex systems, and commonly used coarse-graining methods and variational principles for coarse-graining are derived as particular cases of the general theory. PMID- 21974509 TI - Marginal states in a cubic autocatalytic reaction. AB - Marginal steady state belongs to a special class of states in nonlinear dynamics. To realize this state we consider a cubic autocatalytic reaction A + 2B -> 3B in a continuous-stirred-tank-reactor, where the flow rate of the reactant A can be controlled to manipulate the dynamical behavior of the open system. We demonstrate that when the flow rate is weakly noisy the autocatalytic reaction admits of a steady state which is marginal in nature and is surrounded by infinite number of periodic trajectories. When the uncatalyzed reaction A -> B is included in the reaction scheme, there exists a marginal steady state which is a critical state corresponding to the point of transition between the flow branch and the equilibrium branch, similar to gas-liquid critical point of transition. This state loses its stability in the weak noise limit. PMID- 21974510 TI - Bond energy analysis revisited and designed toward a rigorous methodology. AB - The present study theoretically revisits and numerically assesses two-body energy decomposition schemes including a newly proposed one. The new decomposition scheme is designed to make the equilibrium bond distance equivalent with the minimum point of bond energies. Although the other decomposition schemes generally predict the wrong order of the C-C bond strengths of C(2)H(2), C(2)H(4), and C(2)H(6), the new decomposition scheme is capable of reproducing the C-C bond strengths. Numerical assessment on a training set of molecules demonstrates that the present scheme exhibits a stronger correlation with bond dissociation energies than the other decomposition schemes do, which suggests that the new decomposition scheme is a reliable and powerful analysis methodology. PMID- 21974511 TI - Monte Carlo and event-driven dynamics of Brownian particles with orientational degrees of freedom. AB - Recently, a simple scaling argument was introduced that allows us to map, with some precautions, Brownian and Monte Carlo dynamics for spherical particles. Here, we extend the scaling to study systems that have orientational degrees of freedom and carefully asses its validity over a wide region of temperature and density. Our work allows us to devise a Brownian Monte Carlo algorithm that produces, to a good approximation, physically meaningful trajectories with a minimum programming effort, although at the expense of some sampling efficiency. PMID- 21974512 TI - Mathematical analysis of the boundary-integral based electrostatics estimation approximation for molecular solvation: exact results for spherical inclusions. AB - We analyze the mathematically rigorous BIBEE (boundary-integral based electrostatics estimation) approximation of the mixed-dielectric continuum model of molecular electrostatics, using the analytically solvable case of a spherical solute containing an arbitrary charge distribution. Our analysis, which builds on Kirkwood's solution using spherical harmonics, clarifies important aspects of the approximation and its relationship to generalized Born models. First, our results suggest a new perspective for analyzing fast electrostatic models: the separation of variables between material properties (the dielectric constants) and geometry (the solute dielectric boundary and charge distribution). Second, we find that the eigenfunctions of the reaction-potential operator are exactly preserved in the BIBEE model for the sphere, which supports the use of this approximation for analyzing charge-charge interactions in molecular binding. Third, a comparison of BIBEE to the recent GBepsilon theory suggests a modified BIBEE model capable of predicting electrostatic solvation free energies to within 4% of a full numerical Poisson calculation. This modified model leads to a projection-framework understanding of BIBEE and suggests opportunities for future improvements. PMID- 21974513 TI - Projected quasiparticle theory for molecular electronic structure. AB - We derive and implement symmetry-projected Hartree-Fock-Bogoliubov (HFB) equations and apply them to the molecular electronic structure problem. All symmetries (particle number, spin, spatial, and complex conjugation) are deliberately broken and restored in a self-consistent variation-after-projection approach. We show that the resulting method yields a comprehensive black-box treatment of static correlations with effective one-electron (mean-field) computational cost. The ensuing wave function is of multireference character and permeates the entire Hilbert space of the problem. The energy expression is different from regular HFB theory but remains a functional of an independent quasiparticle density matrix. All reduced density matrices are expressible as an integration of transition density matrices over a gauge grid. We present several proof-of-principle examples demonstrating the compelling power of projected quasiparticle theory for quantum chemistry. PMID- 21974514 TI - Instanton calculations of tunneling splittings for water dimer and trimer. AB - We investigate the ability of the recently developed ring-polymer instanton (RPI) method [J. O. Richardson and S. C. Althorpe, J. Chem. Phys. 134, 054109 (2011)] to treat tunneling in water clusters. We show that the RPI method is easy to extend to treat tunneling between more than two minima, using elementary graph theory. Tests of the method on water dimer and trimer yield a set of instanton periodic orbits which correspond to all known tunneling pathways in these systems. Splitting patterns obtained from the orbits are in good overall agreement with experiment. The agreement is closer for the deuterated than for the protonated clusters, almost certainly because the main approximation in the calculations is neglect of anharmonicity perpendicular to the tunneling path. All the calculations were performed on a desktop computer, which suggests that similar calculations will be possible on much larger clusters. PMID- 21974515 TI - A parallelizable block cellular automaton for the study of diffusion of binary mixtures containing CO2 in microporous materials. AB - We applied a method based on a block cellular automaton (BCA) algorithm to the study of diffusion of various binary mixtures adsorbed in a model microporous material, such as zeolite ZK4. Our aim was to test the capability of our model to cope with systems in which more than one species is present, using a set of parameters based on heuristic considerations from the molecular dynamics (MD) results present in the literature. A rigorous methodology for the assignment of suitable adsorption energies and diffusion activation barriers for our BCA has not been developed yet, nonetheless the results were quite interesting at this stage and we obtained a good qualitative agreement with MD data in the literature. The mixtures we investigated contain CO(2), which causes the so called segregation-effect, a strong suppression of self-diffusivity of co adsorbed species. This effect gives rise to relevant problems in the application of some well established and robust methods, while our model proved to be able to reproduce both the common features and the segregation anomaly in the trends of diffusion. PMID- 21974516 TI - Ab initio potential energy surface and bound states for the Kr-OCS complex. AB - The first ab initio potential energy surface of the Kr-OCS complex is developed using the coupled-cluster singles and doubles with noniterative inclusion of connected triples [CCSD(T)]. The mixed basis sets, aug-cc-pVTZ for the O, C, and S atom, and aug-cc-pVQZ-PP for the Kr atom, with an additional (3s3p2d1f) set of midbond functions are used. A potential model is represented by an analytical function whose parameters are fitted numerically to the single point energies computed at 228 configurations. The potential has a T-shaped global minimum and a local linear minimum. The global minimum occurs at R = 7.146 a(0), theta = 105.0 degrees with energy of -270.73 cm(-1). Bound state energies up to J = 9 are calculated for three isotopomers (82)Kr-OCS, (84)Kr-OCS, and (86)Kr-OCS. Analysis of the vibrational wavefunctions and energies suggests the complex can exist in two isomeric forms: T-shaped and quasi-linear. The calculated transition frequencies and spectroscopic constants of the three isotopomers are in good agreement with the experimental values. PMID- 21974517 TI - Pulsed discharge jet electronic spectroscopy of the aluminum dicarbide (AlC2) free radical. AB - Laser-induced fluorescence and wavelength resolved emission spectra of the C (2)B(2)-X (2)A(1) band system of the gas phase aluminum dicarbide free radical have been obtained using the pulsed discharge jet technique. The radical was produced by electron bombardment of a precursor mixture of trimethylaluminum in high-pressure argon. The three vibrational frequencies of T-shaped AlC(2) have been determined in both the combining states along with several of the anharmonicity constants. The 0(0)(0) band has been recorded with high resolution and rotationally analyzed. The spectrum is complicated by partially resolved spin rotation and aluminum hyperfine splittings. Where necessary, we have fixed the spin-rotation constants used in the rotational analysis at the values predicted by density functional theory. The derived molecular structures are: r(0)('')(C-C) = 1.271(2) A, r(0)('')(Al-C) = 1.926(1) A, theta(")(C-Al-C) = 38.5(2) degrees , r(0)(')(C-C) = 1.323(2) A, r(0)(')(Al-C) = 1.934(1) A, and theta(')(C-Al-C) = 40.0(2) degrees . Unlike SiC(2), aluminum dicarbide shows no spectroscopic evidence of facile isomerization to the linear structure in the ground electronic state. PMID- 21974518 TI - Physical properties of small water clusters in low and moderate electric fields. AB - Likely candidates for the lowest minima of water clusters (H(2)O)(N) for N <= 20 interacting with a uniform electric field strength in the range E <= 0.6 V/A have been identified using basin-hopping global optimization. Two water-water model potentials were considered, namely TIP4P and the polarizable Dang-Chang potential. The two models produce some consistent results but also exhibit significant differences. The cluster internal energy and dipole moment indicate two varieties of topological transition in the structure of the global minimum as the field strength is increased. The first takes place at low field strengths (0.1 V/A 10) usually forming helical structures. PMID- 21974519 TI - Optical purification of a mixture of chiral forms by dimer formation. AB - We introduce a readily executable method for the optical purification of "scalemic" (non 50%-50%) mixtures of chiral molecules of opposite handedness ("enantiomers"). The method relies on the formation of two types of dimers, (R-R or S-S) "homodimers" and (R-S) "heterodimers." The selectivity is linked to the difference in sign recently discovered by us to exist between certain transition dipole matrix elements of opposite enantiomers. This sign difference results in differences in spectral propensity rules: In homodimers, transitions from the ground state can only take place to inversion symmetric excited states, while in the heterodimer the transitions are much more likely to proceed to antisymmetric excited states (although for heterodimers weak transitions to symmetric states might exist). These opposing propensity rules fully explain the observed large differences in the spectra of homodimers vs. heterodimers, which exist despite the almost identical energy levels positions. We illustrate the general concepts by computationally demonstrating the optically induced enantio-purification of scalemic mixtures of the hydropropionic C(3)H(6)O(3) (lactic) acid. PMID- 21974520 TI - Intramolecular vibrational dynamics in S1 p-fluorotoluene. I. Direct observation of doorway states. AB - Picosecond time-resolved photoelectron spectroscopy is used to investigate intramolecular vibrational redistribution (IVR) following excitation of S(1) 18a(1) in p-fluorotoluene (pFT) at an internal energy of 845 cm(-1), where nu(18a) is a ring bending vibrational mode. Characteristic oscillations with periods of 8 ps and 5 ps are observed in the photoelectron signal and attributed to coupling between the initially excited zero-order bright state and two doorway states. Values for the coupling coefficients connecting these three vibrational states have been determined. In addition, an exponential change in photoelectron signal with a lifetime of 17 ps is attributed to weaker couplings with a bath of dark states that play a more significant role during the latter stages of IVR. A tier model has been used to assign the most strongly coupled doorway state to S(1) 17a(1) 6a(2)('), where nu(17a) is a CH out-of-plane vibrational mode and 6a(2)(') is a methyl torsional level. This assignment signifies that a torsion vibration coupling mechanism mediates the observed dynamics, thus demonstrating the important role played by the methyl torsional mode in accelerating IVR. PMID- 21974521 TI - Spectroscopy and thermochemistry of a jet-cooled open-shell polyene: 1,4 pentadienyl radical. AB - The 1,4-pentadienyl (vinylallyl) radical has been observed for the first time by optical spectroscopy. An excitation spectrum is recorded on m/z 67 by resonant two-color two-photon ionization spectroscopy. Several bands are observed with the origin transition identified at 19 449 cm(-1). The spectrum is assigned by a comparison with ab initio frequencies calculated at the CASPT2/cc-pVTZ level of theory, with an accompanying Franck-Condon calculation of the excitation spectrum, including Dushinsky mixing. The b(1) and a(2) outer C-C bond torsional modes are calculated to halve in frequency upon electronic excitation, bringing about their appearance in the excitation spectrum. This can be readily understood by considering the torsional sensitivity of the frontier molecular orbital energies. High-level quantum chemical calculations of the radical stabilization energy, resulting in a value of nearly 120 kJ mol(-1), provide quantitative confirmation that this radical is highly stabilized. PMID- 21974522 TI - Low energy (0-10 eV) electron driven reactions in the halogenated organic acids CCl3COOH, CClF2COOH, and CF3CHNH2COOH (trifluoroalanine). AB - Negative ion formation following resonant electron attachment to the three title molecules is studied by means of a beam experiment with mass spectrometric detection of the anions. All three molecules exhibit a pronounced resonance in the energy range around 1 eV which decomposes by the loss of a neutral hydrogen atom thereby generating the closed shell anion (M-H)(-) (or RCOO(-)), a reaction which is also a common feature in the non-substituted organic acids. The two chlorine containing molecules CCl(3)COOH and CClF(2)COOH exhibit an additional strong and narrow resonance at very low energy (close to 0 eV) which decomposes by the cleavage of the C-Cl bond with the excess charge finally localised on either of the two fragments Cl(-) and (M-Cl)(-). This reaction is by two to three orders of magnitude more effective than hydrogen loss. Apart from these direct bond cleavages (C-Cl, O-H) resonant attachment of subexcitation electrons trigger additional remarkably complex unimolecular decompositions leading, e.g., to the formation of the bihalide ions ClHCl(-) and ClHF(-) from CCl(3)COOH and CClF(2)COOH, respectively, or the loss of a neutral CF(2) unit from trifluoroalanine thereby generating the fluoroglycine radical anion. These reactions require substantial rearrangement in the transitory negative ion, i.e., the cleavage of different bonds and formation of new bonds. F(-) from both chlorodifluoroacetic acid and trifluoroalanine is formed at comparatively low intensity (more than three orders of magnitude less than Cl(-) from the chlorine containing molecules) and predominantly within a broad resonant feature around 7 8 eV characterised as core excited resonance. PMID- 21974523 TI - Interplay between charge and vibrational delocalization in cationic helium clusters. AB - The stable structures and low temperature thermodynamics of cationic helium clusters are investigated theoretically using a diatomics-in-molecules model for the potential energy surfaces and a computational framework in which both electronic and nuclear degrees of freedom are treated on a quantum mechanical footing. While the charge is generally carried by two atoms, vibrational delocalization significantly spreads out the charge over multiple isomers for clusters containing five or more helium atoms. Our calculations indicate that large clusters are essentially fluid with a well-defined solvation shell around the charged core. PMID- 21974524 TI - Energy levels, Auger branching ratios, and radiative rates of the core-excited states of B-like carbon. AB - Energy levels, Auger branching ratios, and radiative rates of the core-excited states of B-like carbon are calculated by the saddle-point variation and saddle point complex-rotation methods. Relativistic and mass polarization corrections are included using first-order perturbation theory. Calculated Auger channel energies and branching ratios are used to identify high-resolution Auger spectrum in the 300-keV C(+) -> CH(4) collision experiment. It is found that Auger decay of these five-electron core-excited states gives significant contributions to Auger spectrum in the range of 238-280 eV. PMID- 21974525 TI - Torsional vibrational structure of the propene radical cation studied by high resolution photoelectron spectroscopy. AB - The pulsed-field-ionization zero-kinetic-energy photoelectron spectra of the X(+2)A(")<-X(1)A' transition of CH(3)CHCH(2) (propene), CD(3)CDCD(2), and several partially deuterated isotopomers have been recorded in the region of their adiabatic ionization thresholds and up to 2000 cm(-1) of internal energy of the cations. The vibrational structure has been assigned on the basis of the frequency shifts resulting from deuteration of selected sites of the propene molecule. Two highly anharmonic progressions have been identified and assigned to the two torsional modes of the propene cation, the methyl and methylene torsions. The positions of the torsional levels could be approximately reproduced using one dimensional models, allowing a semi-quantitative description of the potential energy surface along each torsional coordinate. The observation of forbidden vibrational bands and the analysis of their partially resolved rotational contours reveal the importance of the vibronic coupling between the X(+2)A(") and the A(+2)A(') states mediated by the methylene (nu(20)) and methyl (nu(21)) torsional modes. PMID- 21974526 TI - The nu2 bending vibrational structure of the X2Sigma+ state of MgNC. AB - We have generated MgNC in supersonic free jet expansions and observed the laser induced fluorescence (LIF) of the A(2)Pi-X(2)Sigma(+) transition. We measured the LIF dispersed spectra from the single vibronic levels of the A(2)Pi electronic state of MgNC, following excitation of each nu(2) bending vibronic band observed, i.e., the kappa series of the (0,v(2)('),0)-(0,0,0), v(2)(') = 0, 1, 2, 4, and 6 vibronic bands. In the vibrational structure in the dispersed fluorescence spectra measured, the long progression of the nu(2) bending mode in the X(2)Sigma(+) state is identified, e.g., up to v(2)('')=14 in the (0,6,0) (0,v(2)(''),0) spectrum. This enables us to derive the potential curve of the nu(2) bending mode in the X(2)Sigma(+) state. We used two kinds of models to obtain the potential curve; (I) the customary formula expressed in the polynomial series of the (v(2)('')+(d(2)/2)) term and (II) the internal rotation model. The potential curve derived from model (I) indicates the convergence of the bending vibrational levels at about 800 cm(-1) from the vibrationless level of MgNC, which may correspond to the barrier height of the isomerization reaction, MgNC ? MgCN, in the X(2)Sigma(+) state. Model (II) gives a simple picture for the isomerization reaction pathway with a barrier height of about 630 cm(-1) from the vibrationless level of the more stable species, MgNC. This shows that the v(2)('')=8 bending vibrational level of MgNC is already contaminated by the v(2)('')=2 bending vibrational level of the isomer, MgCN, and implies that the isomerization reaction begins at the v(2) ('')=8 level. The bending potential surface and the isomerization reaction pathway, MgNC ? MgCN, in the X(2)Sigma(+) state are discussed by comparing the potential derived in this study with the surface obtained by quantum chemical calculation. PMID- 21974527 TI - Franck-Condon simulation, including anharmonicity, of the photodetachment spectrum of P2H(-): restricted-spin coupled-cluster single-double plus perturbative triple and unrestricted-spin coupled-cluster single-double plus perturbative triple -F12x potential energy functions of P2H and P2H(-). AB - Geometry optimization and harmonic vibrational frequency calculations have been carried out on the X(2)A(') state of P(2)H and the X(1)A(') state of P(2)H(-) using the restricted-spin coupled-cluster single-double plus perturbative triple excitation [RCCSD(T)] and explicitly correlated unrestricted-spin coupled-cluster single-double plus perturbative triple excitation [UCCSD(T)-F12x] methods. For RCCSD(T) calculations, basis sets of up to the augmented correlation-consistent polarized valence quintuple-zeta (aug-cc-pV5Z) quality were employed, and contributions from extrapolation to the complete basis set limit and from core correlation of the P 2s(2)2p(6) electrons were also included. For UCCSD(T)-F12x calculations, different atomic orbital basis sets of triple-zeta quality with different associated complementary auxiliary basis sets and different geminal Slater exponents were used. When the P 2s(2)2p(6) core electrons were correlated in these F12x calculations, appropriate core-valence basis sets were employed. In addition, potential energy functions (PEFs) of the X(2)A(') state of P(2)H and the X(1)A(') state of P(2)H(-) were computed at different RCCSD(T) and UCCSD(T) F12x levels, and were used in variational calculations of anharmonic vibrational wavefunctions, which were then utilized to calculate Franck-Condon factors (FCFs) between these two states, employing a method which includes allowance for anharmonicity and Duschinsky rotation. The photodetachment spectrum of P(2)H(-) was then simulated using the computed FCFs. Simulated spectra obtained using the RCCSD(T)/aug-cc-pV5Z and UCCSD(T)-F12x(x = a or b)/aug-cc-pCVTZ PEFs are compared and found to be essentially identical. Based on the computed FCFs, a more detailed assignment of the observed vibrational structure than previously reported, which includes "hot bands," has been proposed. Comparison between simulated and available experimental spectra has been made, and the currently most reliable sets of equilibrium geometrical parameters for P(2)H and its anion have been derived. The photodetachment spectrum of P(2)D, yet to be recorded, has also been simulated. PMID- 21974528 TI - Rotational predissociation of extremely weakly bound atom-molecule complexes produced by Feshbach resonance association. AB - We study the rotational predissociation of atom-molecule complexes with very small binding energy. Such complexes can be produced by Feshbach resonance association of ultracold molecules with ultracold atoms. Numerical calculations of the predissociation lifetimes based on the computation of the energy dependence of the scattering matrix elements become inaccurate when the binding energy is smaller than the energy width of the predissociating state. We derive expressions that represent accurately the predissociation lifetimes in terms of the real and imaginary parts of the scattering length and effective range for molecules in an excited rotational state. Our results show that the predissociation lifetimes are the longest when the binding energy is positive, i.e., when the predissociating state is just above the excited state threshold. PMID- 21974529 TI - Vibrations of H+(D+) in stoichiometric LiNbO3 single crystal. AB - A first principles quantum mechanical calculation of the vibrational energy levels and transition frequencies associated with protons in stoichiometric LiNbO(3) single crystal has been carried out. The hydrogen contaminated crystal has been approximated by a model one obtains by translating a supercell, i.e., a cluster of LiNbO(3) unit cells containing a single H(+) and a Li(+) vacancy. Based on the supercell model an approximate Hamiltonian operator describing vibrations of the proton sublattice embedded in the host crystal has been derived. It is further simplified to a sum of uncoupled Hamiltonian operators corresponding to different wave vectors (ks) and each describing vibrations of a quasi-particle (quasi-proton). The three dimensional (3D) Hamiltonian operator of k=0 has been employed to calculate vibrational levels and transition frequencies. The potential energy surface (PES) entering this Hamiltonian operator has been calculated point wise on a large set of grid points by using density functional theory, and an analytical approximation to the PES has been constructed by non parametric approximation. Then, the nuclear motion Schrodinger equation has been solved by employing the method of discrete variable representation. It has been found that the (quasi-)H(+) vibrates in a strongly anharmonic PES. Its vibrations can be described approximately as a stretching, and two orthogonal bending vibrations. The theoretically calculated transition frequencies agree within 1% with those experimentally determined, and they have allowed the assignment of one of the hitherto unassigned bands as a combination of the stretching and the bending of lower fundamental frequency. PMID- 21974530 TI - Low density mesostructures of confined dipolar particles in an external field. AB - Mesostructures formed by dipolar particles confined between two parallel walls and subjected to an external field are studied by Monte Carlo simulations. The main focus of the work is the structural behavior of the Stockmayer fluid in the low density regime. The dependence of cluster thickness and ordering is estimated as a function of density and wall separation, the two most influential parameters, for large dipole moments and high field strengths. The great sensitivity of the structure to details of the short-range part of the interactions is pointed out. In particular, the attractive part of the Lennard Jones potential is shown to play a major role in driving chain aggregation. The effect of confinement, evaluated by comparison with results for a bulk system, is most pronounced for a short range hard sphere potential. No evidence is found for a novel "gel-like" phase recently uncovered in low density dipolar colloidal suspensions [A. K. Agarwal and A. Yethiraj, Phys. Rev. Lett. 102, 198301 (2009)]. PMID- 21974531 TI - Spectroscopic and computational studies of matrix-isolated iso-CHBr3: structure, properties, and photochemistry of iso-bromoform. AB - Iso-polyhalomethanes are known reactive intermediates that play a pivotal role in the photochemistry of halomethanes in condensed phases. In this work, iso bromoform (iso-CHBr(3)) and its deuterated isotopomer were characterized by matrix isolation infrared and UV/visible spectroscopy, supported by ab initio and density functional theory calculations, to further probe the structure, spectroscopy, and photochemistry of this important intermediate. Selected wavelength laser irradiation of CHBr(3) isolated in Ar or Ne matrices at ~5 K yielded iso-CHBr(3); the observed infrared and UV/visible absorptions are in excellent agreement with computational predictions, and the energies of various stationary points on the CHBr(3) potential energy surface were characterized computationally using high-level methods in combination with correlation consistent basis sets. These calculations show that, while the corresponding minima lie ~200 kJ/mol above the global CHBr(3) minimum, the isomer is bound by some 60 kJ/mol in the gas phase with respect to the CHBr(2) + Br asymptote. The photochemistry of iso-CHBr(3) was investigated by selected wavelength laser irradiation into the intense S(0) -> S(3) transition, which resulted in back photoisomerization to CHBr(3). Intrinsic reaction coordinate calculations confirmed the existence of a first-order saddle point connecting the two isomers, which lies energetically below the threshold of the radical channel. Subsequently, natural bond orbital analysis and natural resonance theory were used to characterize the important resonance structures of the isomer and related stationary points, which demonstrate that the isomerization transition state represents a crossover from dominantly covalent to dominantly ionic bonding. In condensed phases, the ion-pair dominated isomerization transition state structure is preferentially stabilized, so that the barrier to isomerization is lowered. PMID- 21974532 TI - Dynamical transition of glasses: from exact to approximate. AB - We introduce a family of glassy models having a parameter, playing the role of an interaction range, that may be varied continuously to go from a system of particles in d dimensions to a mean-field version of it. The mean-field limit is exactly described by equations conceptually close, but different from, the mode coupling equations. We obtain these by a dynamic virial construction. Quite surprisingly, we observe that in three dimensions, the mean-field behavior is closely followed for ranges as small as one interparticle distance, and still qualitatively for smaller distances. For the original particle model, we expect the present mean-field theory to become, unlike the mode-coupling equations, an increasingly good approximation at higher dimensions. PMID- 21974533 TI - Proton transfer and the mobilities of the H+ and OH- ions from studies of a dissociating model for water. AB - Hydrogen (H(+)) and hydroxide (OH(-)) ions in aqueous solution have anomalously large diffusion coefficients, and the mobility of the H(+) ion is nearly twice that of the OH(-) ion. We describe molecular dynamics simulations of a dissociating model for liquid water based on scaling the interatomic potential for water developed by Ojamae-Shavitt-Singer from ab initio studies at the MP2 level. We use the scaled model to study proton transfer that occurs in the transport of hydrogen and hydroxide ions in acidic and basic solutions containing 215 water molecules. The model supports the Eigen-Zundel-Eigen mechanism of proton transfer in acidic solutions and the transient hyper-coordination of the hydroxide ion in weakly basic solutions at room temperature. The free energy barriers for proton transport are low indicating significant proton delocalization accompanying proton transfer in acidic and basic solutions. The reorientation dynamics of the hydroxide ion suggests changes in the proportions of hyper-coordinated species with temperature. The mobilities of the hydrogen and hydroxide ions and their temperature dependence between 0 and 50 degrees C are in excellent agreement with experiment and the reasons for the large difference in the mobilities of the two ions are discussed. The model and methods described provide a novel approach to studies of liquid water, proton transfer, and acid base reactions in aqueous solutions, channels, and interfaces. PMID- 21974534 TI - Nucleation barriers in tetrahedral liquids spanning glassy and crystallizing regimes. AB - Crystallization and vitrification of tetrahedral liquids are important both from a fundamental and a technological point of view. Here, we study via extensive umbrella sampling Monte Carlo computer simulations the nucleation barriers for a simple model for tetrahedral patchy particles in the regime where open tetrahedral crystal structures (namely, cubic and hexagonal diamond and their stacking hybrids) are thermodynamically stable. We show that by changing the angular bond width, it is possible to move from a glass-forming model to a readily crystallizing model. From the shape of the barrier we infer the role of surface tension in the formation of the crystalline clusters. Studying the trends of the nucleation barriers with the temperature and the patch width, we are able to identify an optimal value of the patch size that leads to easy nucleation. Finally, we find that the nucleation barrier is the same, within our numerical precision, for both diamond crystals and for their stacking forms. PMID- 21974536 TI - First principles calculations on structure, bonding, and vibrational frequencies of SiP2. AB - Pyrite type SiP(2) is reinvestigated by first principles calculations on various levels of functionals including local density approximation, generalized gradient approximation, Becke-Lee-Yang-Parr hybrid functional, and the Hartree-Fock method. SiP(2) is seen as a model compound with molecular [P-P] entities and [SiP(6)] octahedra. Structure and bonding are addressed by electronic structure calculations. Special attention is spent on P-P and Si-P bonds in terms of bond lengths and respective stretching modes from simulated Raman spectra. The electronic structure is analyzed in both direct and momentum space by the electron localization function and site projected density of states. The main goals of this work are to understand the nature of chemical bonding in SiP(2) and to compare and contrast the different methods of calculation. PMID- 21974535 TI - A molecular dynamics investigation of the structural and dynamic properties of the ionic liquid 1-n-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide. AB - Molecular dynamics simulations have been performed to investigate the structure and dynamics of the ionic liquid, 1-n-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([C(4)mim][Tf(2)N]) in the temperature range of 283-460 K. Extensive analysis was carried out to characterize a number of structural and dynamic features. Transport properties were computed using a variety of equilibrium methods that employed the Green-Kubo and Einstein formulations. Nonequilibrium techniques were also used. In general, different methods mostly yielded consistent results, although some differences were observed. Computed self-diffusivities and ionic conductivities tended to be slightly lower than experimental values, while computed viscosities were significantly higher than experiment. Computed thermal conductivities agreed reasonably well with experimental data. Despite these discrepancies, the simulations capture the experimental temperature-dependent trends for all these transport properties. Single ion dynamics were studied by examining diffusional anisotropy, the self-part of the van Hove function, non-Gaussian parameters, and incoherent intermediate scattering functions. It is found that cations diffuse faster than anions and are more dynamically heterogeneous. A clear anisotropy is revealed in cation displacement, with the motion normal to the imidazolium ring plane being the most hindered and the motion along the alkyl chain in the plane of the ring being the most facile. Cations structurally relax faster than anions but they rotationally relax slower than anions. There is a pronounced temperature dependence to the rotational anisotropy of the cations, but only a weak temperature dependence for the anions. The ionic conductivity deviates from the Nernst-Einstein relation due to the correlated motion of cations and anions. The results suggest that the dynamical behavior of this and related ionic liquids is extremely complex and consists of many different modes with widely varying timescales, making the prediction of dynamical trends extremely difficult. PMID- 21974537 TI - Excited-state switching by per-fluorination of para-oligophenylenes. AB - Fluorination has become a versatile route to tune the electronic and optical properties of organic conjugated materials. Herein we report a new phenomenon, excited-state switching by per-fluorination of para-oligophenylenes, placing a low intensity 1(1)B(2) state below the 1(1)B(1) state, giving rise to large Stokes shifts. The switching is attributed to the specific impact of fluorine on the delocalized and localized frontier orbitals as elucidated by quantum-chemical calculations. The sterical demands of the fluorine atom additionally diminish efficient conjugation along the chain, leading to hypsochromic shifts with respect to the unsubstituted counterparts and to a weak chain length dependence of the absorption and unstructured emission spectra and enhanced internal conversion. PMID- 21974538 TI - Nature of phase transitions in crystalline and amorphous GeTe-Sb2Te3 phase change materials. AB - The thermodynamic nature of phase stabilities and transformations are investigated in crystalline and amorphous Ge(1)Sb(2)Te(4) (GST124) phase change materials as a function of pressure and temperature using high-resolution synchrotron x-ray diffraction in a diamond anvil cell. The phase transformation sequences upon compression, for cubic and hexagonal GST124 phases are found to be: cubic -> amorphous -> orthorhombic -> bcc and hexagonal -> orthorhombic -> bcc. The Clapeyron slopes for melting of the hexagonal and bcc phases are negative and positive, respectively, resulting in a pressure dependent minimum in the liquidus. When taken together, the phase equilibria relations are consistent with the presence of polyamorphism in this system with the as-deposited amorphous GST phase being the low entropy low-density amorphous phase and the laser melt quenched and high-pressure amorphized GST being the high entropy high-density amorphous phase. The metastable phase boundary between these two polyamorphic phases is expected to have a negative Clapeyron slope. PMID- 21974539 TI - High resolution quantum cascade laser studies of the nu3 band of methyl fluoride in solid para-hydrogen. AB - Spectra of solid para-H(2) doped with CH(3)F at 1.8 K are studied in the nu(3) region (~1040 cm(-1)) using a quantum cascade laser source. As shown previously, residual ortho-H(2) in the sample (~1000 ppm) gives rise to distinct spectral features due to clusters of the form CH(3)F-(ortho-H(2))(N), with N = 0, 1, 2, 3, etc. Brief annealing at 7 K is found to give narrower spectral lines (>=0.006 cm( 1)) than conventional (5 K) annealing, and causes the N = 3 and 4 lines to fragment into two or more components. The N = 3 line is observed to be particularly stable and persistent. The N = 0 line (no ortho-H(2) neighbors) is resolved into two closely spaced (~0.007 cm(-1)) components which are assigned to the K = 0 and 1 states of CH(3)F rotating around its C(3v) symmetry axis (ortho- and para-CH(3)F, respectively). Similar K-structure is also evident for other lines. Weak but persistent features ("N = 1/2 lines") are observed mid way between N = 0 and 1. PMID- 21974540 TI - Core-softened system with attraction: trajectory dependence of anomalous behavior. AB - In the present article we carry out a molecular dynamics study of the core softened system and show that the existence of the water-like anomalies in this system depends on the trajectory in P-rho-T space along which the behavior of the system is studied. For example, diffusion and structural anomalies are visible along isotherms as a function of density, but disappears along the isochores and isobars as a function of temperature. On the other hand, the diffusion anomaly may be seen along adiabats as a function of temperature, density, and pressure. It should be noted that it may be no signature of a particular anomaly along a particular trajectory, but the anomalous region for that particular anomaly can be defined when all possible trajectories in the same space are examined (for example, signature of diffusion anomaly is evident through the crossing of different isochors. However, there is no signature of diffusion anomaly along a particular isochor). We also analyze the applicability of the Rosenfeld entropy scaling relations to this system in the regions with the water-like anomalies. It is shown that the validity of the Rosenfeld scaling relation for the diffusion coefficient also depends on the trajectory in the P-rho-T space along which the kinetic coefficients and the excess entropy are calculated. PMID- 21974541 TI - Implications of the effective one-component analysis of pair correlations in colloidal fluids with polydispersity. AB - Partial pair-correlation functions of colloidal suspensions with continuous polydispersity can be challenging to characterize from optical microscopy or computer simulation data due to inadequate sampling. As a result, it is common to adopt an effective one-component description of the structure that ignores the differences between particle types. Unfortunately, whether this kind of simplified description preserves or averages out information important for understanding the behavior of the fluid depends on the degree of polydispersity and can be difficult to assess, especially when the corresponding multicomponent description of the pair correlations is unavailable for comparison. Here, we present a computer simulation study that examines the implications of adopting an effective one-component structural description of a polydisperse fluid. The square-well model that we investigate mimics key aspects of the experimental behavior of suspended colloids with short-range, polymer-mediated attractions. To characterize the partial pair-correlation functions and thermodynamic excess entropy of this system, we introduce a Monte Carlo sampling strategy appropriate for fluids with a large number of pseudo-components. The data from our simulations at high particle concentrations, as well as exact theoretical results for dilute systems, show how qualitatively different trends between structural order and particle attractions emerge from the multicomponent and effective one component treatments, even with systems characterized by moderate polydispersity. We examine consequences of these differences for excess-entropy based scalings of shear viscosity, and we discuss how use of the multicomponent treatment reveals similarities between the corresponding dynamic scaling behaviors of attractive colloids and liquid water that the effective one-component analysis does not capture. PMID- 21974542 TI - Experimental study on polarized surface enhanced resonance Raman scattering of rhodamine 6G adsorbed on porous Al2O3 substrates. AB - The polarization properties of surface enhanced resonance Raman scattering (SE(R)RS) of rhodamine 6G molecules, adsorbed to a hexagonally ordered gold nanostructure, are studied with the purpose to discriminate between adsorption sites with different plasmonic properties. The nanostructure is based on a self organizing hexagonally ordered porous Al(2)O(3) substrate sputter-coated with gold. Each hexagonal subunit has D(6h) symmetry, where the symmetry center may act as an isotropic site, whereas the six narrow gaps between the individual Au hemispheres may act as hot-spots. The variation of the depolarization ratio (DPR), measured in resonance for the eight most prominent vibrational modes of the xanthene moiety, is analyzed by rotating the sample. According to theory, the DPR of the SE(R)RS signal obtained from molecules physisorbed in the isotropic sites deviates from the DPR originating from molecules physisorbed in the hot spots in two ways: 1. The DPR associated with the isotropic sites depends differently on the rotation angle than the DPR associated with the hot-spots. 2. The DPR of the SE(R)RS signal obtained from molecules physisorbed in the isotropic sites depends on the nature of the Raman modes, whereas it for molecules physisorbed in the hot-spots is independent of the nature of the Raman modes. By applying the latter in the analysis of the polarized SE(R)RS data, we conclude that the dominating SE(R)RS signal comes from molecules adsorbed in the hot-spots. However, since the DPR's obtained for Raman modes of different symmetry are slightly different, the SE(R)RS signal must contain an additional contribution. Our analysis shows that the small mode-dependent SE(R)RS signal most likely comes from molecules adsorbed in the isotropic sites. The general result that can be derived from the present study is that by measuring the polarization properties in SE(R)RS and SERS it is possible to discriminate between adsorption sites with different plasmonic properties present in a highly symmetric nanostructure, even when the magnitude of the different contributions are highly different. The consequence of the insufficient spatial resolution with respect to a detailed mapping of the substrate often encountered in unpolarized SE(R)RS and in two-photon luminescence microscopy may thereby be circumvented. PMID- 21974543 TI - Dynamics of glass-forming liquids. XV. Dynamical features of molecular liquids that form ultra-stable glasses by vapor deposition. AB - The dielectric relaxation behavior of ethylbenzene (EBZ) in its viscous regime is measured, and the glass transition temperature (T(g) = 116 K) as well as fragility (m = 98) are determined. While the T(g) of EBZ from this work is consistent with earlier results, the fragility is found much higher than what has been assumed previously. Literature data is supplemented by the present results on EBZ to compile the dynamic behavior of those glass formers that are known to form ultra-stable glasses by vapor deposition. These dynamics are contrasted with those of ethylcyclohexane, a glass former for which a comparable vapor deposition failed to produce an equally stable glassy state. In a graph that linearizes Vogel-Fulcher-Tammann behavior, i.e., the derivative of -logtau with respect to T/T(g) raised to the power of -1/2 versus T/T(g), all ultra-stable glass formers fall onto one master curve in a wide temperature range, while ethylcyclohexane deviates for T ? T(g). This result suggests that ultra-stable glass formers share common behavior regarding the dynamics of their supercooled liquid state if scaled to their respective T(g) values, and that fragility and related features are linked to the ability to form ultra-stable materials. PMID- 21974544 TI - Concentration fluctuations in non-isothermal reaction-diffusion systems. II. The nonlinear case. AB - In this paper, we consider a simple reaction-diffusion system, namely, a binary fluid mixture with an association-dissociation reaction between two species. We study fluctuations at hydrodynamic spatiotemporal scales when this mixture is driven out of equilibrium by the presence of a temperature gradient, while still being far away from any chemical instability. This study extends the analysis in our first paper on the subject [J. M. Ortiz de Zarate, J. V. Sengers, D. Bedeaux, and S. Kjelstrup, J. Chem. Phys. 127, 034501 (2007)], where we considered fluctuations in a non-isothermal reaction-diffusion system but still close to equilibrium. The present extension is based on mesoscopic non-equilibrium thermodynamics that we recently developed [D. Bedeaux, I. Pagonabarraga, J. M. Ortiz de Zarate, J. V. Sengers, and S. Kjelstrup, Phys. Chem. Chem. Phys. 12, 12780 (2010)] to derive the law of mass action and fluctuation-dissipation theorems for the random contributions to the dissipative fluxes in the nonlinear macroscopic description. Just as for non-equilibrium fluctuations close to equilibrium, we again find an enhancement of the intensity of the concentration fluctuations in the presence of a temperature gradient. The non-equilibrium concentration fluctuations are in both cases spatially long ranged, with an intensity depending on the wave number q. The intensity exhibits a crossover from a ?q(-4) to a ?q(-2) behavior depending on whether the corresponding wavelength is smaller or larger than the penetration depth of the reacting mixture. This opens a possibility to distinguish between diffusion- or activation-controlled regimes of the reaction experimentally. The important conclusion overall is that non-equilibrium fluctuations in non-isothermal reaction-diffusion systems are always long ranged. PMID- 21974545 TI - Vibrational and orientational dynamics of water in aqueous hydroxide solutions. AB - We report the vibrational and orientational dynamics of water molecules in isotopically diluted NaOH and NaOD solutions using polarization-resolved femtosecond vibrational spectroscopy and terahertz time-domain dielectric relaxation measurements. We observe a speed-up of the vibrational relaxation of the O-D stretching vibration of HDO molecules outside the first hydration shell of OH(-) from 1.7 +/- 0.2 ps for neat water to 1.0 +/- 0.2 ps for a solution of 5 M NaOH in HDO:H(2)O. For the O-H vibration of HDO molecules outside the first hydration shell of OD(-), we observe a similar speed-up from 750 +/- 50 fs to 600 +/- 50 fs for a solution of 6 M NaOD in HDO:D(2)O. The acceleration of the decay is assigned to fluctuations in the energy levels of the HDO molecules due to charge transfer events and charge fluctuations. The reorientation dynamics of water molecules outside the first hydration shell are observed to show the same time constant of 2.5 +/- 0.2 ps as in bulk liquid water, indicating that there is no long range effect of the hydroxide ion on the hydrogen-bond structure of liquid water. The terahertz dielectric relaxation experiments show that the transfer of the hydroxide ion through liquid water involves the simultaneous motion of ~7 surrounding water molecules, considerably less than previously reported for the proton. PMID- 21974546 TI - CO2 adsorption on TiO2(101) anatase: a dispersion-corrected density functional theory study. AB - Adsorption, diffusion, and dissociation of CO(2) on the anatase (101) surface were investigated using dispersion-corrected density functional theory. On the oxidized surface several different local minima were identified of which the most stable corresponds to a CO(2) molecule adsorbed at a five-fold coordinated Ti site in a tilted configuration. Surface diffusion is characterized by relatively small activation barriers. Preferential diffusion takes place along Ti rows and involves a cartwheel type of motion. The presence of a bridging oxygen defect or a surface interstitial Ti atom allows creation of several new strong binding configurations the most stable of which have bent CO(2) structures with simultaneous bonding to two surface Ti atoms. Subsurface oxygen vacancy or interstitial Ti defects are found to enhance the bonding of CO(2) molecules to the surface. CO(2) dissociation from these defect sites is calculated to be exothermic with barriers less than 21 kcal/mol. The use of such defects for catalytic activation of CO(2) on anatase (101) surface would require a mechanism for their regeneration. PMID- 21974547 TI - Resonance and localization effects at a dipolar organic semiconductor interface. AB - The image state manifold of the dipolar organic semiconductor vanadyl naphthalocyanine (VONc) on highly oriented pyrolytic graphite is investigated by angle-resolved two-photon photoemission (AR-TPPE) spectroscopy in the 0-1 monolayer regimes. Interfacial charge-transfer from the image potential state of clean graphite populates a near-resonant VONc anion level, identifiable by the graphite image potential state by its distinct momentum dispersion obtained from AR-TPPE. This affinity level is subject to depolarization by the neighboring molecules, resulting in stabilization of this state with coverage. Near a coverage of one monolayer, a hybrid image potential/anion state is also formed, showing progressive localization with coverage. Intensities for all these features develop rather differently with molecular coverage, pointing towards the different types of charge-transfer interactions at play at this interface. PMID- 21974548 TI - Aggregation of polymer-grafted nanoparticles in good solvents: a hierarchical modeling method. AB - Brownian dynamics simulations are carried out to study the aggregation behavior of polymer-grafted nanoparticles (NPs) in good solvents by using the coarse grained model derived from the all-atom force field, according to the hierarchical modeling strategy, and here PEG-grafted gold nanoparticles (GNPs) were taken as an example. Generally, grafting PEG to the surface of GNPs is to protect them from aggregation in the solution. However, our results reveal that PEG-grafted GNPs may also aggregate when concentration increases. Our simulations indicate that there exists a critical aggregating concentration (CAC), beyond which the PEG-grafted GNPs will aggregate. We further check the effects of grafting density and the length of grafted chains on the aggregation behavior of the grafted GNPs, and find that there exists an optimized length of grafted chain, at which the system has the maximal CAC. Furthermore, the aggregate size of self-assembled mesostructures formed by the grafted GNPs increases with the concentration. Interestingly, it is observed that the aggregation favors to form linear gold nanowires rather than compact gold nanoclusters, and the corresponding mechanism is also addressed. It is expected that this work would provide useful information for the fabrication of metal nanowires and the surface modification of metal nanoparticles. PMID- 21974549 TI - Single-particle and collective excitations in quantum wires made up of vertically stacked quantum dots: zero magnetic field. AB - We report on the theoretical investigation of the elementary electronic excitations in a quantum wire made up of vertically stacked self-assembled InAs/GaAs quantum dots. The length scales (of a few nanometers) involved in the experimental setups prompt us to consider an infinitely periodic system of two dimensionally confined (InAs) quantum dot layers separated by GaAs spacers. The resultant quantum wire is characterized by a two-dimensional harmonic confining potential in the x-y plane and a periodic (Kronig-Penney) potential along the z (or the growth) direction within the tight-binding approximation. Since the wells and barriers are formed from two different materials, we employ the Bastard's boundary conditions in order to determine the eigenfunctions along the z direction. These wave functions are then used to generate the Wannier functions, which, in turn, constitute the legitimate Bloch functions that govern the electron dynamics along the direction of periodicity. Thus, the Bloch functions and the Hermite functions together characterize the whole system. We then make use of the Bohm-Pines' (full) random-phase approximation in order to derive a general nonlocal, dynamic dielectric function. Thus, developed theoretical framework is then specified to work within a (lowest miniband and) two-subband model that enables us to scrutinize the single-particle as well as collective responses of the system. We compute and discuss the behavior of the eigenfunctions, band-widths, density of states, Fermi energy, single-particle and collective excitations, and finally size up the importance of studying the inverse dielectric function in relation with the quantum transport phenomena. It is remarkable to notice how the variation in the barrier- and well-widths can allow us to tailor the excitation spectrum in the desired energy range. Given the advantage of the vertically stacked quantum dots over the planar ones and the foreseen applications in the single-electron devices and in the quantum computation, it is quite interesting and important to explore the electronic, optical, and transport phenomena in such systems. PMID- 21974550 TI - Raman scattering of 4-aminobenzenethiol sandwiched between Ag nanoparticle and macroscopically smooth Au substrate: effects of size of Ag nanoparticles and the excitation wavelength. AB - A nanogap formed by a metal nanoparticle and a flat metal substrate is one kind of "hot site" for surface-enhanced Raman scattering (SERS). Accordingly, although no Raman signal is observable when 4-aminobenzenethiol (4-ABT), for instance, is self-assembled on a flat Au substrate, a distinct spectrum is obtained when Ag or Au nanoparticles are adsorbed on the pendent amine groups of 4-ABT. This is definitely due to the electromagnetic coupling between the localized surface plasmon of Ag or Au nanoparticle with the surface plasmon polariton of the planar Au substrate, allowing an intense electric field to be induced in the gap even by visible light. To appreciate the Raman scattering enhancement and also to seek the optimal condition for SERS at the nanogap, we have thoroughly examined the size effect of Ag nanoparticles, along with the excitation wavelength dependence, by assembling 4-ABT between planar Au and a variable-size Ag nanoparticle (from 20- to 80-nm in diameter). Regarding the size dependence, a higher Raman signal was observed when larger Ag nanoparticles were attached onto 4-ABT, irrespective of the excitation wavelength. Regarding the excitation wavelength, the highest Raman signal was measured at 568 nm excitation, slightly larger than that at 632.8 nm excitation. The Raman signal measured at 514.5 and 488 nm excitation was an order of magnitude weaker than that at 568 nm excitation, in agreement with the finite-difference time domain simulation. It is noteworthy that placing an Au nanoparticle on 4-ABT, instead of an Ag nanoparticle, the enhancement at the 568 nm excitation was several tens of times weaker than that at the 632.8 nm excitation, suggesting the importance of the localized surface plasmon resonance of the Ag nanoparticles for an effective coupling with the surface plasmon polariton of the planar Au substrate to induce a very intense electric field at the nanogap. PMID- 21974551 TI - A low energy electron microscopy study of the initial growth, structure, and thermal stability of 4,4'-biphenyldicarboxylic acid domains on Cu(001). AB - The growth of 4,4(')-biphenyldicarboxylic acid (BDA) on Cu(001) has been studied using low energy electron microscopy and selective area low energy electron diffraction. The emergence of large islands and hydrogen bonding to perpendicularly oriented, adjacent molecules is confirmed. The two benzene rings of adsorbed BDA are twisted along the molecular axis. Unconventional growth of the domains, followed by a second nucleation stage, is observed at room temperature. This unanticipated feature is attributed to the accumulation of stress in the islands. Ostwald ripening in the films and the decay of BDA domains at 448 K exhibits features that are consistent with diffusion limited behavior. PMID- 21974552 TI - C-N coupling on transition metal surfaces: a density functional theory study. AB - We have investigated the formation of C-N bonds from individual atoms and single hydrogenated moieties on a series of transition metals. These reactions play a role in HCN formation at high oxygen coverage, also known as Andrussow oxidation, and they are fundamental to understand the ability of other materials to form part of alloys where Pt is the major component. Dehydrogenations take place quite easily under these high oxygen conditions and thus, the C+N, HC+N, and N+CH recombinations to form HCN or its isomer CNH might represent the rate-limiting steps for the reaction. For all the metals in the present study we have found that the activation energy for the reactions between H(x)C and NH(y) (x,y = 0,1) involved in C-N formation follow a linear relationship with the adsorption energy of the N atom. This is due to the common nature of all these transition states, where N-containing fragments get activated from three-fold hollow sites to bridge positions. The slopes of the linear dependence, though, depend on the valence of the N fragment, i.e., smaller slopes are found for NH moieties with respect to N ones. PMID- 21974553 TI - The effect of doping on the energetics and quantum conductance in graphene nanoribbons with a metallocene adsorbate. AB - Based on a PBE-D2 calculation that empirically includes van der Waals interactions to the standard GGA approximation of Perdew, Berke, and Ernzerhof, we have investigated the adsorption of ferrocene or ruthenocene on pristine and X doped graphene (GrS) or graphene nanoribbons (GNRs), where X (=B or N) is a p type or n-type heteroatom. First, we find that van der Waals interactions play a dominant role in the adsorption. Second, we find that metallocene adsorption on doped GNRs introduces different effects in the low-bias conductance, not far from the linear response regime, of GNRs depending upon the doping type. Adsorption on undoped or p-type GNRs brings about a slight reduction in conductance due to an introduction of quasi-bound states just below the Fermi level. No appreciable reduction is expected in n-type GNRs because those states are introduced far below the Fermi level. PMID- 21974554 TI - Structure-dependent band dispersion in epitaxial anthracene films. AB - The intermolecular band dispersion related to the highest occupied molecular orbital of epitaxial anthracene multilayer films on single-crystalline Bi(0001) has been measured using angle-resolved ultraviolet photoelectron spectroscopy. By comparing the dispersion to that of anthracene multilayers on Cu(110) [F. Bussolotti, Y. Yamada-Takamura, and R. Friedlein, Phys. Rev. B 80, 153402 (2009)], it is shown how the transfer integrals and the difference in on-site energies depend on lattice parameters and how this, in turn, affects the band curvature along high-symmetry directions. PMID- 21974555 TI - Density functional theory of size-dependent surface tension of Lennard-Jones fluid droplets using a double well type Helmholtz free energy functional. AB - A double well type Helmholtz free energy density functional and a model density profile for a two phase vapor-liquid system are used to obtain the size-dependent interfacial properties of the vapor-liquid interface at coexistence condition along the lines of van der Waals and Cahn and Hilliard density functional formalism of the interface. The surface tension, temperature-density curve, density profile, and thickness of the interface of Lennard-Jones fluid droplet vapor equilibrium, as predicted in this work are reported. The planar interfacial properties, obtained from consideration of large radius of the liquid drop, are in good agreement with the results of other earlier theories and experiments. The same free energy model has been tested by solving the equations numerically, and the results compare well with those from the use of model density profile. PMID- 21974556 TI - Supercooled dynamics of grain boundary particles in two-dimensional colloidal crystals. AB - We experimentally investigate the dynamics of particles constituting grain boundaries in a two-dimensional colloidal crystal, using video-microscopy. A clear plateau in the mean square displacement of the grain boundary particles is found, followed by an upswing indicative of cage breaking. The van Hove correlation functions and the non-Gaussian parameter show that grain boundary particle dynamics are highly heterogeneous. Furthermore, we identified clusters of cooperatively moving particles and analyzed the time-dependence of the weight averaged mean cluster size. We find good correlation between the behavior of the mean square displacement, and the time dependence of the non-Gaussian parameter and the cluster size, as also reported for various supercooled systems. Our results therefore provide experimental support for the similarity between particle dynamics in grain boundaries and in supercooled liquids as suggested by recent computer simulations. PMID- 21974557 TI - Re-examining the properties of the aqueous vapor-liquid interface using dispersion corrected density functional theory. AB - First-principles molecular dynamics simulations, in which the forces are computed from electronic structure calculations, have great potential to provide unique insight into structure, dynamics, electronic properties, and chemistry of interfacial systems that is not available from empirical force fields. The majority of current first-principles simulations are driven by forces derived from density functional theory with generalized gradient approximations to the exchange-correlation energy, which do not capture dispersion interactions. We have carried out first-principles molecular dynamics simulations of air-water interfaces employing a particular generalized gradient approximation to the exchange-correlation functional (BLYP), with and without empirical dispersion corrections. We assess the utility of the dispersion corrections by comparison of a variety of structural, dynamic, and thermodynamic properties of bulk and interfacial water with experimental data, as well as other first-principles and force field-based simulations. PMID- 21974558 TI - Average relaxation time of internal spectrum for carbosilane dendrimers: nuclear magnetic resonance studies. AB - A new theoretical description of the interior mobility of carbosilane dendrimers has been tested. Experiments were conducted using measurements of the (1)H NMR spin-lattice relaxation time, T(1H), of two-, three- and four-generation carbosilane dendrimers with three different types of terminal groups in dilute chloroform solutions. Temperature dependences of the NMR relaxation rate, 1/T(1H), were obtained for the internal CH(2)-groups of the dendrimers in the range of 1/T(1H) maximum, allowing us to directly evaluate the average time of the internal spectrum for each dendrimer. It was found that the temperature of 1/T(1H) maximum is practically independent of the number of generations, G; therefore, the theoretical prediction was confirmed experimentally. In addition, the average time of the internal spectrum of carbosilane dendrimers was found to be near 0.2 ns at room temperature, and this value correlates well with the values previously obtained for other dendrimer structures using other experimental techniques. PMID- 21974559 TI - Towards a mesoscopic model of water-like fluids with hydrodynamic interactions. AB - We present a mesoscopic lattice model for non-ideal fluid flows with directional interactions, mimicking the effects of hydrogen bonds in water. The model supports a rich and complex structural dynamics of the orientational order parameter, and exhibits the formation of disordered domains whose size and shape depend on the relative strength of directional order and thermal diffusivity. By letting the directional forces carry an inverse density dependence, the model is able to display a correlation between ordered domains and low density regions, reflecting the idea of water as a denser liquid in the disordered state than in the ordered one. PMID- 21974560 TI - Confinement in nanopores can destabilize alpha-helix folding proteins and stabilize the beta structures. AB - Protein folding in confined media has attracted wide attention over the past decade due to its importance in both in vivo and in vitro applications. Currently, it is generally believed that protein stability increases by decreasing the size of the confining medium, if its interaction with the confining walls is repulsive, and that the maximum folding temperature in confinement occurs for a pore size only slightly larger than the smallest dimension of the folded state of a protein. Protein stability in pore sizes, very close to the size of the folded state, has not however received the attention that it deserves. Using detailed, 0.3-ms-long molecular dynamics simulations, we show that proteins with an alpha-helix native state can have an optimal folding temperature in pore sizes that do not affect the folded-state structure. In contradiction to the current theoretical explanations, we find that the maximum folding temperature occurs in larger pores for smaller alpha-helices. In highly confined pores the free energy surface becomes rough, and a new barrier for protein folding may appear close to the unfolded state. In addition, in small nanopores the protein states that contain the beta structures are entropically stabilized, in contrast to the bulk. As a consequence, folding rates decrease notably and the free energy surface becomes rougher. The results shed light on many recent experimental observations that cannot be explained by the current theories, and demonstrate the importance of entropic effects on proteins' misfolded states in highly confined environments. They also support the concept of passive effect of chaperonin GroEL on protein folding by preventing it from aggregation in crowded environment of biological cells, and provide deeper clues to the alpha -> beta conformational transition, believed to contribute to Alzheimer's and Parkinson's diseases. The strategy of protein and enzyme stabilization in confined media may also have to be revisited in the case of tight confinement. For in silico studies of protein folding in confined media, use of non-Go potentials may be more appropriate. PMID- 21974561 TI - Accelerating atomic-level protein simulations by flat-histogram techniques. AB - Flat-histogram techniques provide a powerful approach to the simulation of first order-like phase transitions and are potentially very useful for protein studies. Here, we test this approach by implicit solvent all-atom Monte Carlo (MC) simulations of peptide aggregation, for a 7-residue fragment (GIINFEQ) [corrected] of the Cu/Zn superoxide dismutase 1 protein (SOD1). In simulations with 8 chains, we observe two distinct aggregated/non-aggregated phases. At the midpoint temperature, these phases coexist, separated by a free-energy barrier of height 2.7 k(B)T. We show that this system can be successfully studied by carefully implemented flat-histogram techniques. The frequency of barrier crossing, which is low in conventional canonical simulations, can be increased by turning to a two-step procedure based on the Wang-Landau and multicanonical algorithms. PMID- 21974562 TI - Photon statistics in blinking fluorescence of single PPV-PPyV molecule. AB - A theoretical six-level model for blinking fluorescence of single PPV-PPyV copolymer molecule excited by CW-laser light is proposed. The model has been chosen in accordance with the following facts found in the Paul Barbara group experiment: (i) alternation of two types of fluorescence with moderate and strong levels of emission, (ii) existence of "dark" states with no fluorescence, (iii) linear dependence of inverse on-interval duration on laser intensity, and (iv) existence of laser intensity independent off-intervals. Relations between the distribution function w''(N, T) for photons emitted by a single molecule, the distribution function w'(N, T) for photons arriving at photomultiplier tube (PMT) and photo-electric pulse distribution w(N, T) created in a PMT are discussed. The theory is able to describe pulse distribution function w(N, T) measured experimentally at signal acquisition time T = 0.1 s. Values of all rate constants of the model have been found from comparison of the theory with the experiment. Distributions w(on, off)(t) of on- and off-times and distribution w(N, T) of pulses have been calculated for infrequent and frequent inter-conformational jumps in single copolymer molecule. PMID- 21974563 TI - Influence of mobile DNA-protein-DNA bridges on DNA configurations: coarse-grained Monte-Carlo simulations. AB - A large literature exists on modeling the influence of sequence-specific DNA binding proteins on the shape of the DNA double helix in terms of one or a few fixed constraints. This approach is inadequate for the many proteins that bind DNA sequence independently, and that are present in very large quantities rather than as a few copies, such as the nucleoid proteins in bacterial cells. The influence of such proteins on DNA configurations is better modeled in terms of a great number of mobile constraints on the DNA. Types of constraints that mimic the influence of various known non-specifically DNA binding proteins include DNA bending, wrapping, and bridging. Using Monte-Carlo simulations, we here investigate the influence of (non-interacting) mobile DNA-protein-DNA bridges on the configurations of a 1000 bp piece of linear DNA, for both homogeneous DNA and DNA with an intrinsic planar bend. Results are compared to experimental data on the bacterial nucleoid protein H-NS that forms DNA-protein-DNA bridges. In agreement with data on H-NS, we find very strong positioning of DNA-protein-DNA bridges in the vicinity of planar bends. H-NS binds to DNA very cooperatively, but for non-interacting bridges we only find a moderate DNA-induced clustering. Finally, it has been suggested that H-NS is an important contributor to the extreme condensation of bacterial DNA into a nucleoid structure, but we find only a moderate compaction of DNA coils with increasing numbers of non-interacting bridges. Our results illustrate the importance of quantifying the various effects on DNA configurations that have been proposed for proteins that bind DNA sequence independently. PMID- 21974567 TI - Optical scanning system for light-absorption measurement of deep biological tissue. AB - A noncontact near-infrared scanning system for multi-distance absorption measurement of deep biological tissue was developed. An 808-nm laser, whose focal point on the surface of biological tissue is controlled by a galvano scanner, is used as a light source. A phosphor is placed at a detection focal point on the tissue surface. The light that propagates through tissue and exits from the tissue surface beneath the phosphor excites the phosphor. The fluorescence emitted from the phosphor is detected by an avalanche photodiode. The system is used to measure 20 points on tissue surface at which source-detector (S-D) distances are 7-45 mm (with 2-mm intervals). Neither the light source nor the detector contacts the tissue surface. The system was validated by using it to measure the absorption change of an absorber (which is embedded in a deep layer of a tissue-simulating phantom) while the surface-layer thickness of the phantom was changed from 1 to 12 mm. It was demonstrated that both the relative absorption change of the absorber and the absolute thickness of the surface layer can be estimated from the measured optical-density change (DeltaOD) and the dependence of DeltaOD on S-D distance, respectively. PMID- 21974566 TI - Invited article: millimeter-wave bolometer array receiver for the Atacama pathfinder experiment Sunyaev-Zel'dovich (APEX-SZ) instrument. AB - The Atacama pathfinder experiment Sunyaev-Zel'dovich (APEX-SZ) instrument is a millimeter-wave cryogenic receiver designed to observe galaxy clusters via the Sunyaev-Zel'dovich effect from the 12 m APEX telescope on the Atacama plateau in Chile. The receiver contains a focal plane of 280 superconducting transition-edge sensor (TES) bolometers instrumented with a frequency-domain multiplexed readout system. The bolometers are cooled to 280 mK via a three-stage helium sorption refrigerator and a mechanical pulse-tube cooler. Three warm mirrors, two 4 K lenses, and a horn array couple the TES bolometers to the telescope. APEX-SZ observes in a single frequency band at 150 GHz with 1' angular resolution and a 22' field-of-view, all well suited for cluster mapping. The APEX-SZ receiver has played a key role in the introduction of several new technologies including TES bolometers, the frequency-domain multiplexed readout, and the use of a pulse-tube cooler with bolometers. As a result of these new technologies, the instrument has a higher instantaneous sensitivity and covers a larger field-of-view than earlier generations of Sunyaev-Zel'dovich instruments. The TES bolometers have a median sensitivity of 890 MUK(CMB)?s (NEy of 3.5 * 10(-4) ?s). We have also demonstrated upgraded detectors with improved sensitivity of 530 MUK(CMB)?s (NEy of 2.2 * 10( 4) ?s). Since its commissioning in April 2007, APEX-SZ has been used to map 48 clusters. We describe the design of the receiver and its performance when installed on the APEX telescope. PMID- 21974568 TI - TRIPLE Q: a three channel quantum cascade laser absorption spectrometer for fast multiple species concentration measurements. AB - A compact and transportable three channel quantum cascade laser system (TRIPLE Q) based on mid-infrared absorption spectroscopy has been developed for time resolved plasma diagnostics. The TRIPLE Q spectrometer encompasses three independently controlled quantum cascade lasers (QCLs), which can be used for chemical sensing, particularly for gas phase analysis of plasmas. All three QCLs are operated in the intra-pulse mode with typical pulse lengths of the order of 150 ns. Using a multiplexed detection, a time resolution shorter than 1 MUs can be achieved. Hence, the spectrometer is well suited to study kinetic processes of multiple infrared active compounds in reactive plasmas. A special data processing and analysis technique has been established to account for time jitter effects of the infrared emission of the QCLs. The performance of the TRIPLE Q system has been validated in pulsed direct current plasmas containing N(2)O/air and NO(2)/air. PMID- 21974569 TI - High signal-to-noise Fourier transform spectroscopy with light emitting diode sources. AB - A temperature tuned light emitting diode (LED) has several advantages over conventional sources for Fourier transform spectroscopy. The large radiation density of LEDs, concentrated in a small spectral region, is ideal for high resolution Fourier transform spectroscopy where a high signal-to-noise (S/N) ratio is desired. A simple, inexpensive LED source leads to a superior performance at high resolutions exceeding that of a tungsten halogen lamp, in the visible region of spectrum. PMID- 21974570 TI - Linac Coherent Light Source soft x-ray materials science instrument optical design and monochromator commissioning. AB - We present the x-ray optical design of the soft x-ray materials science instrument at the Linac Coherent Light Source, consisting of a varied line-spaced grating monochromator and Kirkpatrick-Baez refocusing optics. Results from the commissioning of the monochromator are shown. A resolving power of 3000 was achieved, which is within a factor of two of the design goal. PMID- 21974571 TI - Demonstration of a room temperature 2.48-2.75 THz coherent spectroscopy source. AB - We report the first demonstration of a continuous wave coherent source covering 2.48-2.75 THz, with greater than 10% instantaneous tuning bandwidth and having 1 14 MUW of output power at room temperature. This source is based on a 91.8-101.8 GHz synthesizer followed by a power amplifier and three cascaded frequency triplers. It demonstrates for the first time that purely electronic solid-state sources can generate a useful amount of power in a region of the electromagnetic spectrum where lasers (solid state or gas) were previously the only available coherent sources. The bandwidth, agility, and operability of this THz source have enabled wideband, high resolution spectroscopic measurements of water, methanol, and carbon monoxide with a resolution and signal-to-noise ratio unmatched by any other existing system, providing new insight in the physics of these molecules. Furthermore, the power and optical beam quality are high enough to observe the Lamb-dip effect in water. The source frequency has an absolute accuracy better than 1 part in 10(12) and the spectrometer achieves sub-Doppler frequency resolution better than 1 part in 10(8). The harmonic purity is better than 25 dB. This source can serve as a coherent signal for absorption spectroscopy, a local oscillator for a variety of heterodyne systems and can be used as a method for precision control of more powerful but much less frequency agile quantum mechanical terahertz sources. PMID- 21974572 TI - A tilt sensor with a compact dimension based on a long-period fiber grating. AB - A tilt sensor with a compact dimension based on a long-period fiber grating (LPG) is proposed and experimentally demonstrated. The LPG is fixed in a rigid Plexi glass tubular with a slant orientation and half of the LPG is immersed into the NaCl aqueous solutions, whereas the other half is exposed in air. The tilt angle is obtained by monitoring the dip wavelength shift of the LPG, which changes gradually when the immersed length of the LPG varies with the tilt angle. Experimental results show that the average sensitivity 0.077 nm/ degrees is achieved within the measurement range from -30 degrees to 30 degrees at the static measurement. PMID- 21974573 TI - Repetitive operation of switchless transverse flow transversely excited atmosphere CO2 lasers. AB - The enhanced preionisation efficiency of a mutually coupled parallel spark preioniser has been exploited to achieve switchless operation of a transversely excited atmosphere (TEA) CO(2) laser in the conventional transverse gas flow configuration. This made the laser more compatible to repetitive operation and the satisfactory performance of a switchless TEA CO(2) laser of ~8 cc active volume is reported here up to a maximum repetition rate of 100 Hz at a gas replenishment factor of ~2. PMID- 21974574 TI - A traveling wave decelerator for neutral polar molecules. AB - Recently, a decelerator for neutral polar molecules has been presented that operates on the basis of macroscopic, three-dimensional, traveling electrostatic traps [A. Osterwalder, S. A. Meek, G. Hammer, H. Haak, and G. Meijer, Phys. Rev. A 81, 051401 (2010)]. In the present paper, a complete description of this decelerator is given, with emphasis on the electronics and the mechanical design. Experimental results showing the transverse velocity distributions of guided molecules are shown and compared to trajectory simulations. An assessment of non adiabatic losses is made by comparing the deceleration signals from (13)CO with those from (12)CO and with simulated signals. PMID- 21974575 TI - Single-shot velocity-map imaging of attosecond light-field control at kilohertz rate. AB - High-speed, single-shot velocity-map imaging (VMI) is combined with carrier envelope phase (CEP) tagging by a single-shot stereographic above-threshold ionization (ATI) phase-meter. The experimental setup provides a versatile tool for angle-resolved studies of the attosecond control of electrons in atoms, molecules, and nanostructures. Single-shot VMI at kHz repetition rate is realized with a highly sensitive megapixel complementary metal-oxide semiconductor camera omitting the need for additional image intensifiers. The developed camera software allows for efficient background suppression and the storage of up to 1024 events for each image in real time. The approach is demonstrated by measuring the CEP-dependence of the electron emission from ATI of Xe in strong (~10(13) W/cm(2)) near single-cycle (4 fs) laser fields. Efficient background signal suppression with the system is illustrated for the electron emission from SiO(2) nanospheres. PMID- 21974576 TI - Ultra-low noise single-photon detector based on Si avalanche photodiode. AB - We report operation and characterization of a lab-assembled single-photon detector based on commercial silicon avalanche photodiodes (PerkinElmer C30902SH, C30921SH). Dark count rate as low as 5 Hz was achieved by cooling the photodiodes down to -80 degrees C. While afterpulsing increased as the photodiode temperature was decreased, total afterpulse probability did not become significant due to detector's relatively long deadtime in a passively-quenched scheme. We measured photon detection efficiency >50% at 806 nm. PMID- 21974577 TI - High-precision semiconductor wavelength sensor based on a double-layer photo diode. AB - We present a wavelength sensor setup for monochromatic visible light, based on the double-layer photo diode WS-7.56. Employing high-precision electronics and automatic compensation of different error sources, we achieve a measurement accuracy of +/-0.025 nm with a resolution below 0.01 nm. The described apparatus is particularly suited for the determination of small laser frequency deviations in atomic physics experiments. Various design issues as well as error sources and diode characteristics are discussed. PMID- 21974578 TI - Spectrographic temperature measurement of a high power breakdown arc in a high pressure gas switch. AB - A procedure for obtaining an approximate temperature value of conducting plasma generated during self-break closure of a RIMFIRE gas switch is described. The plasma is in the form of a breakdown arc which conducts approximately 12 kJ of energy in 1 MUs. A spectrographic analysis of the trigger-section of the 6-MV RIMFIRE laser triggered gas switch used in Sandia National Laboratory's "Z Machine" has been made. It is assumed that the breakdown plasma has sufficiently approached local thermodynamic equilibrium allowing a black-body temperature model to be applied. This model allows the plasma temperature and radiated power to be approximated. The gas dielectric used in these tests was pressurized SF(6). The electrode gap is set at 4.59 cm for each test. The electrode material is stainless steel and insulator material is poly(methyl methacrylate). A spectrum range from 220 to 550 nanometers has been observed and calibrated using two spectral irradiance lamps and three spectrograph gratings. The approximate plasma temperature is reported. PMID- 21974579 TI - K-shell emission x-ray imaging of Z-pinch plasmas with a pinhole and a logarithmic spiral crystal. AB - An in-chamber, mini x-ray imaging instrument employs a pinhole and a logarithmic spiral crystal has been developed for obtaining K-shell line images of the imploding aluminum wire array on the "Yang" accelerator. The logarithmic spiral crystal acts as a monochromator and a non-dispersive mirror that reflects the pinhole image to a x-ray film detector with a very narrow photon energy bandwidth (<1 eV, mainly determined by the width of rocking curve of the crystal). Two imaging configurations with the use of Quartz (10 10) crystal and Mica (002) crystal are designed, respectively, to image the Al Ly(alpha2) line (1727.7 eV) emission and Al He(alpha) intercombination line (1588.3 eV) emission. The primary experimental data corresponding to these two configurations are presented and discussed. PMID- 21974580 TI - Spatially resolved charge-state and current-density distributions at the extraction of an electron cyclotron resonance ion source. AB - In this paper we present our measurements of charge-state and current-density distributions performed in very close vicinity (15 mm) of the extraction of our hexapole geometry electron cyclotron resonance ion source. We achieved a relatively high spatial resolution reducing the aperture of our 3D-movable extraction (puller) electrode to a diameter of only 0.5 mm. Thus, we are able to limit the source of the extracted ion beam to a very small region of the plasma electrode's hole (O = 4 mm) and therefore to a very small region of the neutral plasma sheath. The information about the charge-state distribution and the current density in the plane of the plasma electrode at each particular position is conserved in the ion beam. We determined the total current density distribution at a fixed coaxial distance of only 15 mm to the plasma electrode by remotely moving the small-aperture puller electrode which contained a dedicated Faraday cup (FC) across the aperture of the plasma electrode. In a second measurement we removed the FC and recorded m/q-spectra for the different positions using a sector magnet. From our results we can deduce that different ion charge-states can be grouped into bloated triangles of different sizes and same orientation at the extraction with the current density peaking at centre. This confirms observations from other groups based on simulations and emittance measurements. We present our measurements in detail and discuss possible systematic errors. PMID- 21974581 TI - Development of a radio-frequency ion beam source for fast-ion studies on the large plasma device. AB - A helium ion beam source (23 kV/2.0 A) has been constructed for studying fast-ion physics in the cylindrical magnetized plasma of the large plasma device (LAPD). An inductive RF source produces a 10(19) m(-3) density plasma in a ceramic dome. A multi-aperture, rectangular (8 cm * 8 cm) three-grid system extracts the ion beam from the RF plasma. The ion beam is injected at a variety of pitch angles with Alfvenic speeds in the LAPD. The beam current is intense enough to excite magnetic perturbations in the ambient plasma. Measurements of the ion beam profile were made to achieve an optimum beam performance and a reliable source operation was demonstrated on the LAPD. PMID- 21974582 TI - Lithium plasma emitter for collisionless magnetized plasma experiment. AB - This paper presents a newly developed lithium plasma emitter, which can provide quiescent and low-temperature collisionless conditions for magnetized plasma experiments. This plasma emitter generates thermal emissions of lithium ions and electrons to produce a lithium plasma. Lithium type beta-eucryptite and lanthanum hexaboride (LaB(6)) powders were mixed and directly heated with a tungsten heater to synthesize ion and electron emissions. As a result, a plasma with a diameter of ~15 cm was obtained in a magnetic mirror configuration. The typical range of electron density was 10(12)-10(13) m(-3) and that of electron temperature was 0.1 0.8 eV with the emitter operation temperature of about 1500 K. The amplitude fluctuations for the plasma density were lower than 1%. PMID- 21974583 TI - Plasma-assisted catalytic ionization using porous nickel plate. AB - Hydrogen atomic pair ions, i.e., H(+) and H(-) ions, are produced by plasma assisted catalytic ionization using a porous nickel plate. Positive ions in a hydrogen plasma generated by dc arc discharge are irradiated to the porous plate, and pair ions are produced from the back of the irradiation plane. It becomes clear that the production quantity of pair ions mainly depends on the irradiation current of positive ions and the irradiation energy affects the production efficiency of H(-) ions. PMID- 21974584 TI - A new nonlinear reconstruction method based on total variation regularization of neutron penumbral imaging. AB - Neutron penumbral imaging is a significant diagnostic technique in laser-driven inertial confinement fusion experiment. It is very important to develop a new reconstruction method to improve the resolution of neutron penumbral imaging. A new nonlinear reconstruction method based on total variation (TV) regularization is proposed in this paper. A TV-norm is used as regularized term to construct a smoothing functional for penumbral image reconstruction in the new method, in this way, the problem of penumbral image reconstruction is transformed to the problem of a functional minimization. In addition, a fixed point iteration scheme is introduced to solve the problem of functional minimization. The numerical experimental results show that, compared to linear reconstruction method based on Wiener filter, the TV regularized nonlinear reconstruction method is beneficial to improve the quality of reconstructed image with better performance of noise smoothing and edge preserving. Meanwhile, it can also obtain the spatial resolution with 5 MUm which is higher than the Wiener method. PMID- 21974585 TI - A synchronized emissive probe for time-resolved plasma potential measurements of pulsed discharges. AB - A pulsed emissive probe technique is presented for measuring the plasma potential of pulsed plasma discharges. The technique provides time-resolved data and features minimal disturbance of the plasma achieved by alternating probe heating with the generation of plasma. Time resolution of about 20 ns is demonstrated for high power impulse magnetron sputtering (HIPIMS) plasma of niobium in argon. Spatial resolution of about 1 mm is achieved by using a miniature tungsten filament mounted on a precision translational stage. Repeated measurements for the same discharge conditions show that the standard deviation of the measurements is about 1-2 V, corresponding to 4%-8% of the maximum plasma potential relative to ground. The principle is demonstrated for measurements at a distance of 30 mm from the target, for different radial positions, at an argon pressure of 0.3 Pa, a cathode voltage of -420 V, and a discharge current of about 60 A in the steady-state phase of the HIPIMS pulse. PMID- 21974586 TI - Grazing incidence extreme ultraviolet spectrometer fielded with time resolution in a hostile z-pinch environment. AB - This recently developed diagnostic was designed to allow for time-gated spectroscopic study of the EUV radiation (4 nm < lambda < 15 nm) present during harsh wire array z-pinch implosions. The spectrometer utilizes a 25 MUm slit, an array of 3 spherical blazed gratings at grazing incidence, and a microchannel plate (MCP) detector placed in an off-Rowland position. Each grating is positioned such that its diffracted radiation is cast over two of the six total independently timed frames of the MCP. The off-Rowland configuration allows for a much greater spectral density on the imaging plate but only focuses at one wavelength per grating. The focal wavelengths are chosen for their diagnostic significance. Testing was conducted at the Zebra pulsed-power generator (1 MA, 100 ns risetime) at the University of Nevada, Reno on a series of wire array z pinch loads. Within this harsh z-pinch environment, radiation yields routinely exceed 20 kJ in the EUV and soft x-ray. There are also strong mechanical shocks, high velocity debris, sudden vacuum changes during operation, energic ion beams, and hard x-ray radiation in excess of 50 keV. The spectra obtained from the precursor plasma of an Al double planar wire array contained lines of Al IX and AlX ions indicating a temperature near 60 eV during precursor formation. Detailed results will be presented showing the fielding specifications and the techniques used to extract important plasma parameters using this spectrometer. PMID- 21974587 TI - Electron current extraction from a permanent magnet waveguide plasma cathode. AB - An electron cyclotron resonance plasma produced in a cylindrical waveguide with external permanent magnets was investigated as a possible plasma cathode electron source. The configuration is desirable in that it eliminates the need for a physical antenna inserted into the plasma, the erosion of which limits operating lifetime. Plasma bulk density was found to be overdense in the source. Extraction currents over 4 A were achieved with the device. Measurements of extracted electron currents were similar to calculated currents, which were estimated using Langmuir probe measurements at the plasma cathode orifice and along the length of the external plume. The influence of facility effects and trace ionization in the anode-cathode gap are also discussed. PMID- 21974589 TI - X-ray beam induced current method at the laboratory x-ray source. AB - The x-ray beam induced current method (XBIC) is realized on the laboratory x-ray source using the polycapillary x-ray optics. It is shown that rather good images of grain boundaries in Si can be obtained by this method. The parameters of x-ray beam are estimated by the simulation of Schottky diode image. A good correlation between the experimental and calculated grain boundary XBIC contrast is obtained. The possibilities of laboratory source based XBIC method are estimated. PMID- 21974588 TI - Micro axial tomography: a miniaturized, versatile stage device to overcome resolution anisotropy in fluorescence light microscopy. AB - With the development of novel fluorescence techniques, high resolution light microscopy has become a challenging technique for investigations of the three dimensional (3D) micro-cosmos in cells and sub-cellular components. So far, all fluorescence microscopes applied for 3D imaging in biosciences show a spatially anisotropic point spread function resulting in an anisotropic optical resolution or point localization precision. To overcome this shortcoming, micro axial tomography was suggested which allows object tilting on the microscopic stage and leads to an improvement in localization precision and spatial resolution. Here, we present a miniaturized device which can be implemented in a motor driven microscope stage. The footprint of this device corresponds to a standard microscope slide. A special glass fiber can manually be adjusted in the object space of the microscope lens. A stepwise fiber rotation can be controlled by a miniaturized stepping motor incorporated into the device. By means of a special mounting device, test particles were fixed onto glass fibers, optically localized with high precision, and automatically rotated to obtain views from different perspective angles under which distances of corresponding pairs of objects were determined. From these angle dependent distance values, the real 3D distance was calculated with a precision in the ten nanometer range (corresponding here to an optical resolution of 10-30 nm) using standard microscopic equipment. As a proof of concept, the spindle apparatus of a mature mouse oocyte was imaged during metaphase II meiotic arrest under different perspectives. Only very few images registered under different rotation angles are sufficient for full 3D reconstruction. The results indicate the principal advantage of the micro axial tomography approach for many microscopic setups therein and also those of improved resolutions as obtained by high precision localization determination. PMID- 21974590 TI - Atomic force microscopy at ambient and liquid conditions with stiff sensors and small amplitudes. AB - We report on atomic force microscopy (AFM) in ambient and liquid environments with the qPlus sensor, a force sensor based on a quartz tuning fork with an all electrical deflection measurement scheme. Small amplitudes, stiff sensors with bulk diamond tips and high Q values in air and liquid allow to obtain high resolution images. The noise sources in air and liquid are analyzed and compared for standard silicon cantilevers and qPlus sensors. First, epitaxial graphene was imaged in air, showing atomic steps with 3 A height and ridges. As a second sample system, measurements on calcite (CaCO(3)) in liquids were performed in water and polyethylenglycol (PEG). We demonstrate high resolution images of steps in PEG on calcite and nanolithography processes, in particular with frequency modulation AFM the controlled dissolution of calcite monolayers. PMID- 21974591 TI - Whispering-gallery acoustic sensing: characterization of mesoscopic films and scanning probe microscopy applications. AB - Full understanding of the physics underlying the striking changes in viscoelasticity, relaxation time, and phase transitions that mesoscopic fluid like films undergo at solid-liquid interfaces, or under confinement between two sliding solid boundaries, constitutes one of the major challenges in condensed matter physics. Their role in the imaging process of solid substrates by scanning probe microscopy (SPM) is also currently controversial. Aiming at improving the reliability and versatility of instrumentation dedicated to characterize mesoscopic films, a noninvasive whispering-gallery acoustic sensing (WGAS) technique is introduced; its application as feedback control in SPM is also demonstrated. To illustrate its working principle and potential merits, WGAS has been integrated into a SPM that uses a sharp tip attached to an electrically driven 32-kHz piezoelectric tuning fork (TF), the latter also tighten to the operating microscope's frame. Such TF-based SPMs typically monitor the TF's state of motion by electrical means, hence subjected to the effects caused by the inherent capacitance of the device (i.e., electrical resonance differing from the probe's mechanical resonance). Instead, the novelty of WGAS resides in exploiting the already existent microscope's frame as an acoustic cavity (its few centimeter sized perimeter closely matching the operating acoustic wavelength) where standing-waves (generated by the nanometer-sized oscillations of the TF's tines) are sensitively detected by an acoustic transducer (the latter judiciously placed around the microscope's frame perimeter for attaining maximum detection). This way, WGAS is able to remote monitoring, via acoustic means, the nanometer-sized amplitude motion of the TF's tines. (This remote-detection method resembles the ability to hear faint, but still clear, levels of sound at the galleries of a cathedral, despite the extraordinary distance location of the sound source.) In applications aiming at characterizing the dynamics of fluid-like mesoscopic films trapped under shear between the TF probe and the solid substrate, WGAS capitalizes on the well-known fact that the TF's motion is sensitively affected by the shear-forces (the substrate and its adsorbed mesocopic film playing a role) exert on its tip, which occurs when the latter is placed in close proximity to a solid substrate. Thus, WGAS uses a TF as an efficient transducer sandwiched between (i) the probe (that interact with the substrate and mesoscopic film), and (ii) the acoustic cavity (where an assessment of the probe mechanical motion is obtained). In short, WGAS has capability for monitoring probe-sample shear-force interactions via remote acoustic sensing means. In another application, WGAS can also be used as feedback control of the probe's vertical position in SPM. In effect, it is observed that when the microscope's probe stylus approaches a sample, a monotonic change of the WGAS acoustic signal occurs in the last ~20 nm before the probe touches the solid sample's surface, which allows implementing an automated-control of the probe-sample distance for safely scanning the tip across the sample surface. This principle is demonstrated by imaging the topographic features of a standard sample. Finally, it is worth to highlight that this alignment-free acoustic-based method offers a very direct assessment of the probe's mechanical motion state (the mechanical and the WGAS acoustic frequency responses coincide), which makes the WGAS a convenient metrology tool for studying surface interactions, including interfacial friction at the nanometer scale. PMID- 21974592 TI - Optics clustered to output unique solutions: a multi-laser facility for combined single molecule and ensemble microscopy. AB - Optics clustered to output unique solutions (OCTOPUS) is a microscopy platform that combines single molecule and ensemble imaging methodologies. A novel aspect of OCTOPUS is its laser excitation system, which consists of a central core of interlocked continuous wave and pulsed laser sources, launched into optical fibres and linked via laser combiners. Fibres are plugged into wall-mounted patch panels that reach microscopy end-stations in adjacent rooms. This allows multiple tailor-made combinations of laser colours and time characteristics to be shared by different end-stations minimising the need for laser duplications. This setup brings significant benefits in terms of cost effectiveness, ease of operation, and user safety. The modular nature of OCTOPUS also facilitates the addition of new techniques as required, allowing the use of existing lasers in new microscopes while retaining the ability to run the established parts of the facility. To date, techniques interlinked are multi-photon/multicolour confocal fluorescence lifetime imaging for several modalities of fluorescence resonance energy transfer (FRET) and time-resolved anisotropy, total internal reflection fluorescence, single molecule imaging of single pair FRET, single molecule fluorescence polarisation, particle tracking, and optical tweezers. Here, we use a well-studied system, the epidermal growth factor receptor network, to illustrate how OCTOPUS can aid in the investigation of complex biological phenomena. PMID- 21974594 TI - High energy resolution bandpass photon detector for inverse photoemission spectroscopy. AB - We report a bandpass ultraviolet photon detector for inverse photoemission spectroscopy with energy resolution of 82 +/- 2 meV. The detector (Sr(0.7)Ca(0.3)F(2)/acetone) consists of Sr(0.7)Ca(0.3)F(2) entrance window with energy transmission cutoff of 9.85 eV and acetone as detection gas with 9.7 eV photoionization threshold. The response function of the detector, measured using synchrotron radiation, has a nearly Gaussian shape. The n = 1 image potential state of Cu(100) and the Fermi edge of silver have been measured to demonstrate the improvement in resolution compared to the CaF(2)/acetone detector. To show the advantage of improved resolution of the Sr(0.7)Ca(0.3)F(2)/acetone detector, the metal to semiconductor transition in Sn has been studied. The pseudogap in the semiconducting phase of Sn could be identified, which is not possible with the CaF(2)/acetone detector because of its worse resolution. PMID- 21974593 TI - Prototype cantilevers for quantitative lateral force microscopy. AB - Prototype cantilevers are presented that enable quantitative surface force measurements using contact-mode atomic force microscopy (AFM). The "hammerhead" cantilevers facilitate precise optical lever system calibrations for cantilever flexure and torsion, enabling quantifiable adhesion measurements and friction measurements by lateral force microscopy (LFM). Critically, a single hammerhead cantilever of known flexural stiffness and probe length dimension can be used to perform both a system calibration as well as surface force measurements in situ, which greatly increases force measurement precision and accuracy. During LFM calibration mode, a hammerhead cantilever allows an optical lever "torque sensitivity" to be generated for the quantification of LFM friction forces. Precise calibrations were performed on two different AFM instruments, in which torque sensitivity values were specified with sub-percent relative uncertainty. To examine the potential for accurate lateral force measurements using the prototype cantilevers, finite element analysis predicted measurement errors of a few percent or less, which could be reduced via refinement of calibration methodology or cantilever design. The cantilevers are compatible with commercial AFM instrumentation and can be used for other AFM techniques such as contact imaging and dynamic mode measurements. PMID- 21974595 TI - Independently driven four-probe method for local electrical characteristics in organic thin-film transistors under controlled channel potential. AB - We describe an independently driven four-probe method to investigate local channel mobility in organic field-effect transistors (OFETs). In OFET devices, probe-organic contact resistance affects device characteristics even in four probe measurement because a change in contact resistance at the source probe induces a change in channel potential, resulting in different local carrier density. To overcome this problem, we introduced a feedback circuit between the source probe and a channel voltage probe to keep the channel potential constant. We demonstrate four-probe I-V measurement on a pentacene thin film (50 nm thick) under controlled channel potential. The feedback successfully enables us to separate contact resistance and channel resistance even under different contact conditions. We also measured four-probe resistance as a function of gate bias and channel probe position. The present results were in good agreement with two dimensional model calculation by arranging four probes in a defect-free area; the mobility of the pentacene single grain was evaluated to be 0.25 cm(2)/(V s). PMID- 21974596 TI - An instrument for the investigation of actinides with spin resolved photoelectron spectroscopy and bremsstrahlung isochromat spectroscopy. AB - A new system for spin resolved photoelectron spectroscopy and bremsstrahlung isochromat spectroscopy has been built and commissioned at Lawrence Livermore National Laboratory for the investigation of the electronic structure of the actinides. Actinide materials are very toxic and radioactive and therefore cannot be brought to most general user facilities for spectroscopic studies. The technical details of the new system and preliminary data obtained therein will be presented and discussed. PMID- 21974597 TI - Heat transfer simulation and thermal measurements of microfabricated x-ray transparent heater stages. AB - A microfabricated amorphous silicon nitride membrane-based nanocalorimeter is proposed to be suitable for an x-ray transparent sample platform with low power heating and built-in temperature sensing. In this work, thermal characterization in both air and vacuum are analyzed experimentally and via simulation. Infrared microscopy and thermoreflectance microscopy are used for thermal imaging of the sample area in air. While a reasonably large isothermal area is found on the sample area, the temperature homogeneity of the entire sample area is low, limiting use of the device as a heater stage in air or other gases. A simulation model that includes conduction, as well as radiation and convection heat loss, is presented with radiation and convection parameters determined experimentally. Simulated temperature distributions show that the homogeneity can be improved by using a thicker thermal conduction layer or reducing the pressure of the gas in the environment but neither are good solutions for the proposed use. A new simple design that has improved temperature homogeneity and a larger isothermal area while maintaining a thin thermal conduction layer is proposed and fabricated. This new design enables applications in transmission x-ray microscopes and spectroscopy setups at atmospheric pressure. PMID- 21974598 TI - Electrochemical isothermal-capacitance-transient spectroscopy: a new depth profiling method of deep levels. AB - The authors report on a new depth profiling method of deep levels, which we call electrochemical isothermal-capacitance-transient spectroscopy (EICTS). This is combined with electrochemical capacitance-voltage using the Schottky barrier of etchable electrolyte and isothermal-capacitance-transient spectroscopy using the capacitance-transient profile at a fixed temperature. We proved its validity by applying to the ZnSe:N epitaxial film of thickness of more than 1000 nm and comparing the characteristics of an obtained deep level with the results measured by conventional deep-level detection techniques. It is expected that EICTS is very effective to assess the deep levels of wide-bandgap semiconductors that suffer from various point defects and their complexes. PMID- 21974600 TI - Electrical calcium test for moisture barrier evaluation for organic devices. AB - We discuss the electrical calcium test--a method to measure very small rates of water vapor permeation through barrier films with high throughput. The sensitivity range for our design is found to be 10(-5) to 15 g/(m(2) d). Moreover, a closer look at the importance of electrodes series resistance is taken: We show that permeation rates are underestimated if it is neglected. Taking this series resistance and Fickian diffusion into account not only the steady, but also the transient state of the permeation curve can be fitted. Using this approach, permeation barriers with different permeabilities are evaluated leading to water vapor transmission rates well comparable to coulometric measurements. The calcium layer morphology is investigated by atomic force microscopy measurements indicating microscopical inhomogeneities during degradation. Variations of electrode material and calcium layer thickness are carried out to examine their influence on the measured permeation. Additionally, optical and electrical calcium tests are compared. Small differences in the time dependence are observed and discussed. PMID- 21974599 TI - Micromechanical testing with microstrain resolution. AB - Simple test equipment has been developed for studying the elastic limit and plastic deformation of thin metal wires and thin foils (down to 10 MUm) under torsion, tension, and bending. Using load-unload methods and gauge lengths up to 1 m, plastic strain as low as 10(-6) can be measured accurately. PMID- 21974601 TI - Laser ablation-miniature mass spectrometer for elemental and isotopic analysis of rocks. AB - A laser ablation-miniature mass spectrometer (LA-MMS) for the chemical and isotopic measurement of rocks and minerals is described. In the LA-MMS method, neutral atoms ablated by a pulsed laser are led into an electron impact ionization source, where they are ionized by a 70 eV electron beam. This results in a secondary ion pulse typically 10-100 MUs wide, compared to the original 5-10 ns laser pulse duration. Ions of different masses are then spatially dispersed along the focal plane of the magnetic sector of the miniature mass spectrometer (MMS) and measured in parallel by a modified CCD array detector capable of detecting ions directly. Compared to conventional scanning techniques, simultaneous measurement of the ion pulse along the focal plane effectively offers a 100% duty cycle over a wide mass range. LA-MMS offers a more quantitative assessment of elemental composition than techniques that detect ions directly generated by the ablation process because the latter can be strongly influenced by matrix effects that vary with the structure and geometry of the surface, the wavelength of the laser beam, and the not well characterized ionization efficiencies of the elements in the process. The above problems attendant to the direct ion analysis has been minimized in the LA-MMS by analyzing the ablated neutral species after their post-ionization by electron impaction. These neutral species are much more abundant than the directly ablated ions in the ablated vapor plume and are, therefore, expected to be characteristic of the chemical composition of the solid. Also, the electron impact ionization of elements is well studied and their ionization cross sections are known and easy to find in databases. Currently, the LA-MMS limit of detection is 0.4 wt.%. Here we describe LA-MMS elemental composition measurements of various minerals including microcline, lepidolite, anorthoclase, and USGS BCR-2G samples. The measurements of high precision isotopic ratios including (41)K/(39)K (0.077 +/- 0.004) and (29)Si/(28)Si (0.052 +/- 0.006) in these minerals by LA-MMS are also described. The LA-MMS has been developed as a prototype instrument system for space applications for geochemical and geochronological measurements on the surface of extraterrestrial bodies. PMID- 21974602 TI - Design, construction, and testing of a large-cavity, 1-10 GHz Flygare-Balle spectrometer. AB - A large pulsed-beam, Fourier transform microwave spectrometer employing 48 in. diameter mirrors and 35(") (NHS-35) diffusion pump has been constructed at the University of Arizona. The Fabry-Perot-type cavity, using the large mirrors provides Q-values in the 15,000 to 40,000 range. Test spectra were obtained using transverse and coaxial injection of the pulsed-nozzle molecular beams. The measured molecular resonance linewidths were 8 kHz for the transverse injection and 2 kHz for coaxial molecular beam injection. Good signal to noise ratios were obtained for the test signals. Strong lines for butadiene iron tricarbonyl were seen with a single beam pulse (S/N = 5/1). Transitions were measured as low as 900 MHz and some previously unresolved hyperfine structure is now resolved for the butadiene iron tricarbonyl spectra. The spectrometer is operated using a personal computer with LABVIEW programs, with provisions for automatic frequency scanning. The extended, low-frequency range of this spectrometer should make it very useful for making measurements on significantly larger molecules and complexes than have been previously studied. The improved resolution, in the coaxial beam mode, will allow better resolution of hyperfine structure. The large diffusion pump allows a higher beam pulse frequency to compensate for the generally lower sensitivity at lower frequencies. PMID- 21974604 TI - A superconducting gravity gradiometer for measurements from a moving vehicle. AB - A gravity gradiometer designed for operation on an aircraft or ship has been tested in the laboratory. A noise level of 0.53 E (E = 10(-9) s(-2)) rms over a 0.001 to 1 Hz bandwidth has been measured, and the primary error mechanisms have been analyzed and quantified. The design is a continuation in the development of superconducting accelerometer technology at the University of Maryland over more than three decades. A cryogenic instrument presents not only the benefit of reduced thermal noise, but also, the extraordinary stability of superconducting circuits and material properties at very low temperatures. This stability allows precise matching of scale factors and accurate rejection of dynamic errors. The design of the instrument incorporates a number of additional features that further enhance performance in a dynamically noisy environment. PMID- 21974603 TI - A robotics platform for automated batch fabrication of high density, microfluidics-based DNA microarrays, with applications to single cell, multiplex assays of secreted proteins. AB - Microfluidics flow-patterning has been utilized for the construction of chip scale miniaturized DNA and protein barcode arrays. Such arrays have been used for specific clinical and fundamental investigations in which many proteins are assayed from single cells or other small sample sizes. However, flow-patterned arrays are hand-prepared, and so are impractical for broad applications. We describe an integrated robotics/microfluidics platform for the automated preparation of such arrays, and we apply it to the batch fabrication of up to eighteen chips of flow-patterned DNA barcodes. The resulting substrates are comparable in quality with hand-made arrays and exhibit excellent substrate-to substrate consistency. We demonstrate the utility and reproducibility of robotics patterned barcodes by utilizing two flow-patterned chips for highly parallel assays of a panel of secreted proteins from single macrophage cells. PMID- 21974606 TI - Accurate measurement of domain wall velocity in amorphous microwires, submicron wires, and nanowires. AB - A new method for measuring the domain wall velocity in a single, ultrathin ferromagnetic amorphous wire with the diameter down to 100 nm is presented. The method has been developed in order to increase the sensitivity in studying the domain wall propagation in bistable magnetic wires in a wide range of field amplitudes, with much larger values of the applied field as compared to those employed when studying the wall propagation in typical amorphous microwires. The large fields required to propagate the domain walls in ultrathin wires are able to nucleate new domain walls in the samples and, therefore, they can affect the accuracy of the entire measurement. The proposed experimental setup prevents such situations by using a number of complex pick-up coils, which allow the detection of the direction of the wall propagation along with the precise measurement of the domain wall velocity. The newly developed method is especially important now, when large effort is devoted to the development of domain wall logic devices based on ultrathin magnetic wires and nanowires. PMID- 21974607 TI - Interface shear microrheometer with an optically driven oscillating probe particle. AB - We report the first experimental demonstration of an active interfacial shear microrheometer (ISMR) that uses a particle trapped by oscillating optical tweezers (OT) to probe the shear modulus G(s)(*)(omega) of a gas/liquid interface. The most significant advantages of the oscillating OT in a rheology study are: (1) very high sensitivity compared to other active microrheology methods and (2) the ability to measure both the real and imaginary components of the complex shear modulus without relying on the use of Kramers-Kronig relation, which can be problematic at low frequencies for most of the passive methods. We demonstrate the utilities of our ISMR in two case studies: (1) a 1,2-dipalmitoyl sn-glycero-3-phosphocholine monolayer and (2) a composite of poly(styrene sulfonate) and dioctadecyldimethylammonium at the air/water interface in regimes where no other active instruments can explore. PMID- 21974608 TI - An anisotropic magneto resistive sensor with set/reset field. AB - Using a set/reset magnetic field, an anisotropic magneto resistive (AMR) magnetic field sensing system was developed to reduce the low frequency noise of an AMR sensor. The magnetic field resolution of the AMR sensor was improved by about three times at the frequencies below 30 Hz and a magnetic field resolution of about 150 pT/?Hz was obtained at 1 Hz. For magnetic particle detection using an AMR sensor with set/reset method, the thermal disturbance effect was canceled well and the signal-to-noise ratio was improved by about three times. PMID- 21974609 TI - Static voltage distribution between turns of secondary winding of air-core spiral strip transformer and its application. AB - The static voltage distribution between winding turns has great impact on output characteristics and lifetime of the air-core spiral strip pulse transformer (ACSSPT). In this paper, winding inductance was calculated by electromagnetic theory, so that the static voltage distribution between turns of secondary winding of ACSSPT was analyzed conveniently. According to theoretical analysis, a voltage gradient because of the turn-to-turn capacitance was clearly noticeable across the ground turns. Simulation results of Pspice and CST EM Studio codes showed that the voltage distribution between turns of secondary winding had linear increments from the output turn to the ground turn. In experiment, the difference in increased voltage between the ground turns and the output turns of a 20-turns secondary winding is almost 50%, which is believed to be responsible for premature breakdown of the insulation, particularly between the ground turns. The experimental results demonstrated the theoretical analysis and simulation results, which had important value for stable and long lifetime ACSSPT design. A new ACSSPT with improved structure has been used successfully in intense electron beam accelerators steadily. PMID- 21974605 TI - A state observer for the Virgo inverted pendulum. AB - We report an application of Kalman filtering to the inverted pendulum (IP) of the Virgo gravitational wave interferometer. Using subspace method system identification techniques, we calculated a linear mechanical model of Virgo IP from experimental transfer functions. We then developed a Kalman filter, based on the obtained state space representation, that estimates from open loop time domain data, the state variables of the system. This allows the observation (and eventually control) of every resonance mode of the IP mechanical structure independently. PMID- 21974610 TI - LC-circuit calorimetry. AB - We present a new type of calorimeter in which we couple an unknown heat capacity with the aid of Peltier elements to an electrical circuit. The use of an electrical inductance and an amplifier in the circuit allows us to achieve autonomous oscillations, and the measurement of the corresponding resonance frequency makes it possible to accurately measure the heat capacity with an intrinsic statistical uncertainty that decreases as ~t(m)(-3/2) with measuring time t(m), as opposed to a corresponding uncertainty ~t(m)(-1/2) in the conventional alternating current method to measure heat capacities. We have built a demonstration experiment to show the feasibility of the new technique, and we have tested it on a gadolinium sample at its transition to the ferromagnetic state. PMID- 21974611 TI - Nonlinearity characterization of temperature sensing systems for integrated circuit testing by intermodulation products monitoring. AB - This work presents an alternative characterization strategy to quantify the nonlinear behavior of temperature sensing systems. The proposed approach relies on measuring the temperature under thermal sinusoidal steady state and observing the intermodulation products that are generated within the sensing system itself due to its nonlinear temperature-output voltage characteristics. From such intermodulation products, second-order interception points can be calculated as a figure of merit of the measuring system nonlinear behavior. In this scenario, the present work first shows a theoretical analysis. Second, it reports the experimental results obtained with three thermal sensing techniques used in integrated circuits. PMID- 21974612 TI - Comparison between pulsed laser and frequency-domain photoacoustic modalities: signal-to-noise ratio, contrast, resolution, and maximum depth detectivity. AB - In this work, a detailed theoretical and experimental comparison between various key parameters of the pulsed and frequency-domain (FD) photoacoustic (PA) imaging modalities is developed. The signal-to-noise ratios (SNRs) of these methods are theoretically calculated in terms of transducer bandwidth, PA signal generation physics, and laser pulse or chirp parameters. Large differences between maximum (peak) SNRs were predicted. However, it is shown that in practice the SNR differences are much smaller. Typical experimental SNRs were 23.2 dB and 26.1 dB for FD-PA and time-domain (TD)-PA peak responses, respectively, from a subsurface black absorber. The SNR of the pulsed PA can be significantly improved with proper high-pass filtering of the signal, which minimizes but does not eliminate baseline oscillations. On the other hand, the SNR of the FD method can be enhanced substantially by increasing laser power and decreasing chirp duration (exposure) correspondingly, so as to remain within the maximum permissible exposure guidelines. The SNR crossover chirp duration is calculated as a function of transducer bandwidth and the conditions yielding higher SNR for the FD mode are established. Furthermore, it was demonstrated that the FD axial resolution is affected by both signal amplitude and limited chirp bandwidth. The axial resolution of the pulse is, in principle, superior due to its larger bandwidth; however, the bipolar shape of the signal is a drawback in this regard. Along with the absence of baseline oscillation in cross-correlation FD-PA, the FD phase signal can be combined with the amplitude signal to yield better axial resolution than pulsed PA, and without artifacts. The contrast of both methods is compared both in depth-wise (delay-time) and fixed delay time images. It was shown that the FD method possesses higher contrast, even after contrast enhancement of the pulsed response through filtering. PMID- 21974613 TI - Experimental research on a modular miniaturization nanoindentation device. AB - Nanoindentation technology is developing toward the in situ test which requires miniaturization of indentation instruments. This paper presents a miniaturization nanoindentation device based on the modular idea. It mainly consists of macro adjusting mechanism, x-y precise positioning platform, z axis precise driving unit, and the load-depth measuring unit. The device can be assembled with different forms and has minimum dimensions of 200 mm * 135 mm * 200 mm. The load resolution is about 0.1 mN and the displacement resolution is about 10 nm. A new calibration method named the reference-mapping method is proposed to calibrate the developed device. Output performance tests and indentation experiments indicate the feasibility of the developed device and calibration method. This paper gives an example that combining piezoelectric actuators with flexure hinge to realize nanoindentation tests. Integrating a smaller displacement sensor, a more compact nanoindentation device can be designed in the future. PMID- 21974614 TI - Probing liquid distribution in partially saturated porous materials with hydraulic admittance. AB - The distribution of two immiscible fluids in a complex porous material during displacement is often central to understanding its function. Characterization of this distribution is traditionally determined via optically transparent flow cells. However, for opaque or thin porous materials of the order of hundreds of microns, optical visualization proves to be difficult and requires sophisticated imaging techniques that are expensive and difficult to come by. We describe here a bench-top tool that dynamically probes the hydraulic pathways leading to each free-interface within a single capillary and a bundle of seven capillaries at various saturations (i.e., hydraulic path lengths). A small volumetric displacement was applied to each interface such that the interfaces remained pinned at the capillary walls and the resultant oscillatory pressure drop was measured to determine the hydraulic admittance at each applied oscillation frequency. When the magnitude of the hydraulic admittance was plotted vs. applied oscillation frequency, a resonance peak was found for each degenerately filled capillary. The corresponding peaks were represented by a half-loop (100% filled) and full loops (partially filled) in a Nyquist plot. We compared the theoretical and measured admittance curves and found good agreement for both capillary systems at high filled states. The theoretical predictions became worse when the hydraulic path length was comparable to the capillary radius. The analysis for the hydraulic admittance of a bundle of capillaries is developed here and experimentally validated for the first time. PMID- 21974615 TI - A battery-operated, stabilized, high-energy pulsed electron gun for the production of rare gas excimers. AB - We report on the design of a new type of hot-filament electron gun delivering fairly high current (a few hundreds of MU A) at high voltage (up to 100 kV) in continuous or pulsed mode. Its novel features are that the filament is heated by means of a pack of rechargeable batteries floated atop the high-voltage power supply in order to get rid of bulky isolation transformers, and that the filament current and, hence, the electron gun current, is controlled by a feedback circuit including a superluminescent diode decoupled from the high voltage by means of an optical fiber. This electron gun is intended for general purposes, although we have especially developed it to meet the needs of our experiment on the infrared emission spectroscopy of rare gas excimers. Our experiment requires that the charge injection into the sample is pulsed and constant and stable in time. The new electron gun can deliver several tens of nC per pulse of electrons of energy up to 100 keV into the sample cell. The new design also eliminates ripples in the emission current and ensures up to 12 h of stable performance. PMID- 21974616 TI - Distortion in the thermal noise spectrum and quality factor of nanomechanical devices due to finite frequency resolution with applications to the atomic force microscope. AB - The thermal noise spectrum of nanomechanical devices is commonly used to characterize their mechanical properties and energy dissipation. This spectrum is measured from finite time series of Brownian motion of the device, which is windowed and Fourier transformed. Here, we present a theoretical and experimental investigation of the effect of such finite sampling on the measured device quality factor. We prove that if no spectral window is used, the thermal noise spectrum retains its original Lorentzian distribution but with a reduced quality factor, indicating an apparent enhancement in energy dissipation. A simple analytical formula is derived connecting the true and measured quality factors - this enables extraction of the true device quality factor from measured data. Common windows used to reduce spectral leakage are found to distort the (true) Lorentzian shape, potentially making fitting problematic. These findings are expected to be of particular importance for devices with high quality factors, where spectral resolution can be limited in practice. Comparison and validation using measurements on atomic force microscope cantilevers are presented. PMID- 21974617 TI - The techniques of metallic foil electrically exploding driving hypervelocity flyer to more than 10 km/s for shock wave physics experiments. AB - Electrical explosion of metallic foil or wire is widely used to the fields of material science (preparation of nao-meter materials), dynamics of materials, and high energy density physics. In this paper, the techniques of gaining hypervelocity flyer driven by electrical explosion of metallic foil were researched, which are used to study dynamics of materials and hypervelocity impact modeling of space debris. Based on low inductance technologies of pulsed storage energy capacitor, detonator switch and parallel plate transmission lines with solid films insulation, two sets of experimental apparatuses with storage energy of 14.4 kJ and 40 kJ were developed for launching hypervelocity flyer. By means of the diagnostic technologies of velocity interferometer system for any reflectors and fibre-optic pins, the hypervelocity polyester (Mylar) flyers were gained. For the apparatus of 14.4 kJ, flyer of diameter phi6 ~ phi10 mm and thickness of 0.1 ~ 0.2 mm was accelerated to the hypervelocity of 10 ~ 14 km/s. And for the apparatus of 40 kJ, flyer of diameter phi20 ~ 30 mm and thickness of 0.2 mm was launched to the velocity of 5 ~ 8 km/s. The flatness of the flyer is not more than 34 ns for the flyer with diameter of 20 mm, and less than 22 ns for the flyer with diameter of 10 mm. Based on the Lagrange hydrodynamic code, one dimensional simulation was done by introducing database of equation of states, discharging circuit equation and Joule heat equation, and modifying energy equation. The simulation results are well agreed with the experimental results in accelerating processing. The simulation results can provide good advices in designing new experiments and developing new experimental devices. Finally, some experiments of materials dynamics and hypervelocity impact of space debris were done by using the apparatus above. The results show that the apparatus of metallic foil electrically exploding driving hypervelocity flyer is a good and versatile tool for shock dynamics. PMID- 21974618 TI - A novel algorithm combining oversampling and digital lock-in amplifier of high speed and precision. AB - Because of a large amount of arithmetic in the standard digital lock-in detection, a high performance processor is needed to implement the algorithm in real time. This paper presents a novel algorithm that integrates oversampling and high-speed lock-in detection. The algorithm sets the sampling frequency as a whole-number multiple of four of the input signal frequency, and then uses the common downsampling technology to lower the sampling frequency to four times of the input signal frequency. It could effectively remove the noise interference and improve the detection accuracy. After that the phase sensitive detector is implemented. It simply does the addition and subtraction on four points in the period of same phase and replaces almost all the multiplication operations to speed up digital lock-in detection calculation substantially. Furthermore, the correction factor is introduced to improve the calculation accuracy of the amplitude, and an error caused by the algorithm in theory can be eliminated completely. The results of the simulation and actual experiments show that the novel algorithm combining digital lock-in detection and oversampling not only has the high precision, but also has the unprecedented speed. In our work, the new algorithm is suitable for the real-time weak signal detection in the general microprocessor not just digital signal processor. PMID- 21974619 TI - Etched multimode microfiber knot-type loop interferometer refractive index sensor. AB - We propose a novel refractive index sensor based on multimode microfiber knot type loop (NL) interferometer. The middle portion (~5 cm) of a 15 cm long multimode fiber is etched in 48% hydrofluoric acid to reduce its diameter to ~12 MUm. A NL of diameter <1 mm is made from the etched fiber. The ends of etched fiber are spliced with single-mode fibers for launching and detecting light from the NL interferometer. The NL introduces path differences to produce interferometric spectra with free spectral range ~16 nm. The spectrum shifts as the surrounding refractive index of the loop is changed by adding chemicals. We observe the highest sensitivity of the NL interferometer ~172 nm/RIU (refractive index unit) at a refractive index value 1.370 as obtained experimentally using commonly available chemicals. The design could be used as simple, low cost, and highly sensitive biological and chemical sensor. PMID- 21974620 TI - Multipurpose high-pressure high-temperature diamond-anvil cell with a novel high precision guiding system and a dual-mode pressurization device. AB - A novel diamond-anvil cell (DAC) design has been constructed and tested for in situ applications at high-pressure (HP) operations and has proved to be suitable even for HP sample environments at non-ambient temperature conditions. The innovative high-precision guiding mechanism, comparable to a dog clutch, consists of perpendicular planar sliding-plane elements and is integrated directly into the base body of the cylindrically shaped DAC. The combination of two force generating devices, i.e., mechanical screws and an inflatable gas membrane, allows the user to choose independently between, and to apply individually, two different forcing mechanisms for pressure generation. Both mechanisms are basically independent of each other, but can also be operated simultaneously. The modularity of the DAC design allows for an easy exchange of functional core element groups optimized not only for various analytical in situ methods but also for HP operation with or without high-temperature (HT) application. For HP-HT experiments a liquid cooling circuit inside the specific inner modular groups has been implemented to obtain a controlled and limited heat distribution within the outer DAC body. PMID- 21974621 TI - Examination of gas desorption by B4C resin for use in neutron scattering experiment. AB - Gas desorption rates for several types of B(4)C resins were investigated using a throughput method. The investigation was particularly focused on determining the out gas composition, effects of dry air, grain size (density) effects on the gas desorption rates. It is found that water is the main component of out gas and that dry air can effectively reduce gas desorption. PMID- 21974622 TI - Changes in CR-39 proton sensitivity due to prolonged exposure to high vacuums relevant to the National Ignition Facility and OMEGA. AB - When used at facilities like OMEGA and the NIF, CR-39 is exposed to high vacuum environments before and after irradiation by charged particles and neutrons. Using an electrostatic linear accelerator at MIT, studies have been conducted to investigate the effects of high vacuum exposure on the sensitivity of CR-39 to fusion protons in the ~1-9 MeV energy range. High vacuum conditions, of order 10( 5) Torr, experienced by CR-39 samples at these facilities were emulated. It is shown that vacuum exposure times longer than ~16 h before proton irradiation result in a decrease in proton sensitivity, whereas no effect was observed for up to 67 h of vacuum exposure after proton irradiation. CR-39 sensitivity curves are presented for samples with prolonged exposure to high vacuum before and after proton irradiation. PMID- 21974623 TI - A 2 MV Van de Graaff accelerator as a tool for planetary and impact physics research. AB - Investigating the dynamical and physical properties of cosmic dust can reveal a great deal of information about both the dust and its many sources. Over recent years, several spacecraft (e.g., Cassini, Stardust, Galileo, and Ulysses) have successfully characterised interstellar, interplanetary, and circumplanetary dust using a variety of techniques, including in situ analyses and sample return. Charge, mass, and velocity measurements of the dust are performed either directly (induced charge signals) or indirectly (mass and velocity from impact ionisation signals or crater morphology) and constrain the dynamical parameters of the dust grains. Dust compositional information may be obtained via either time-of-flight mass spectrometry of the impact plasma or direct sample return. The accurate and reliable interpretation of collected spacecraft data requires a comprehensive programme of terrestrial instrument calibration. This process involves accelerating suitable solar system analogue dust particles to hypervelocity speeds in the laboratory, an activity performed at the Max Planck Institut fur Kernphysik in Heidelberg, Germany. Here, a 2 MV Van de Graaff accelerator electrostatically accelerates charged micron and submicron-sized dust particles to speeds up to 80 km s(-1). Recent advances in dust production and processing have allowed solar system analogue dust particles (silicates and other minerals) to be coated with a thin conductive shell, enabling them to be charged and accelerated. Refinements and upgrades to the beam line instrumentation and electronics now allow for the reliable selection of particles at velocities of 1 80 km s(-1) and with diameters of between 0.05 MUm and 5 MUm. This ability to select particles for subsequent impact studies based on their charges, masses, or velocities is provided by a particle selection unit (PSU). The PSU contains a field programmable gate array, capable of monitoring in real time the particles' speeds and charges, and is controlled remotely by a custom, platform independent, software package. The new control instrumentation and electronics, together with the wide range of accelerable particle types, allow the controlled investigation of hypervelocity impact phenomena across a hitherto unobtainable range of impact parameters. PMID- 21974624 TI - The magnetic-distortion probe: velocimetry in conducting fluids. AB - A new type of velocimeter, capable of local velocity measurements in conducting fluids, is introduced. The principle of the "magnetic-distortion probe" is based on the measurement of the induced magnetic field by the flow of a conducting fluid in the vicinity of a localized magnetic field. The new velocimeter has no moving parts, and can be enclosed in a sealed cap, easing the implementation in harsh environments, such as liquid metals. The proposed method allows one to probe both the continuous part and fluctuations of the velocity, the temporal and spatial resolution being linked to the actual geometric configuration of the probe. A prototype probe has been tested in a gallinstan pipe flow and in a fully turbulent flow of liquid gallium generated by the counter rotation of two coaxial impellers in a cylinder. The signals have been compared to a reference potential probe and show very good agreement both for time-averaged velocities and turbulent fluctuations. The prototype is shown to detect motion from a few cm s( 1) to a few m s(-1). Moreover, the use of the magnetic-distortion probe with large-scale applied magnetic field is discussed. PMID- 21974625 TI - An experimental setup for high resolution 10.5 eV laser-based angle-resolved photoelectron spectroscopy using a time-of-flight electron analyzer. AB - We present an experimental setup for laser-based angle-resolved time-of-flight photoemission. Using a picosecond pulsed laser, photons of energy 10.5 eV are generated through higher harmonic generation in xenon. The high repetition rate of the light source, variable between 0.2 and 8 MHz, enables high photoelectron count rates and short acquisition times. By using a time-of-flight analyzer with angle-resolving capabilities, electrons emitted from the sample within a circular cone of up to +/-15 degrees can be collected. Hence, simultaneous acquisition of photoemission data for a complete area of the Brillouin zone is possible. The current photon energy enables bulk sensitive measurements, high angular resolution, and the resulting covered momentum space is large enough to enclose the entire Brillouin zone in cuprate high-T(c) superconductors. Fermi edge measurements on polycrystalline Au shows an energy resolution better than 5 meV. Data from a test measurement of the Au(111) surface state are presented along with measurements of the Fermi surface of the high-T(c) superconductor Bi(2)Sr(2)CaCu(2)O(8 + delta) (Bi2212). PMID- 21974626 TI - Viscosity measurements of liquids under pressure by using the quartz crystal resonators. AB - A quartz crystal viscometer has been developed for measuring viscosity in liquids under pressure. It employs an AT-cut quartz crystal resonator of fundamental frequency 3 MHz inserted in a variable-volume vessel designed for working up to 80 MPa. Viscosity is determined by two methods from resonance frequency and bandwidth measurements along up to eight different overtones. The resonance frequency allows an absolute measurement of the viscosity but leads to an accuracy limited to 5% whereas the bandwidth technique which works in a relative way provides an accuracy of 2%. The techniques were tested by carrying out measurements in two pure compounds: heptane and toluene. Measurement results demonstrate the feasibility of the technique in this viscosity range. The apparatus was also used to determine the viscosity of n-decane with dissolved methane. The results obtained with these mixtures reveal the applicability of the apparatus for reservoir fluids study. PMID- 21974627 TI - A broadband ferromagnetic resonance spectrometer to measure thin films up to 70 GHz. AB - We report the development of a broadband ferromagnetic resonance (FMR) system operating in the frequency range from 10 MHz to 70 GHz using a closed-cycle He refrigeration system for measurements of thin films and micron/nano structures. The system is capable of carrying out measurements in frequency and field domain. Using two coplanar waveguides, it is capable of simultaneously measuring two samples in the out of plane and in plane FMR geometries. The system operates in the temperature range of 27-350 K and is sensitive to less than one atomic monolayer of a single crystal Fe film. PMID- 21974628 TI - Note: updates to an ultra-low noise laser current driver. AB - We describe updates to our current driver design allowing for higher output currents, both positive and negative currents, and updated digital interfacing to the microcontroller. We also discuss measurement of the noise spectral density of the driver with a better technique, showing that the driver's actual current noise density is about an order of magnitude lower than the upper limit we previously determined. PMID- 21974629 TI - Note: simple means for selective removal of the 365 nm line from the Hg spectrum using Dy. AB - The emission spectrum of mercury has a notable line at about 365 nm under both low and medium-high pressure conditions. A simple filter based on a solution of dysprosium ions, Dy(3+), is shown to be very useful for applications of Hg-light sources where this line is unwanted. The presented filter is cheap, robust, and stable towards degradation or bleaching - even under intense irradiation. The absorption spectrum for the Dy-filter is presented along with emission spectra from both low-pressure and high-pressure Hg-lamps to illustrate the utility of the technique under best-case and worst-case conditions. Attenuation of the 365 nm spectral line is almost total for the low-pressure source whereas for the high pressure source the attenuation is about a factor of three. PMID- 21974630 TI - Note: an underwater multi-channel plasma array for water sterilization. AB - A simple yet effective method to generate multi-channel plasma array in water is presented in this paper. Thin circular metal disks sandwiched between dielectric layers were used, allowing the production of large-volume underwater plasma array with higher stability. The system can be further scaled up by stacking multiple metal disks, making it suitable for large-scale industrial water treatment. Generation of UV and reactive species was identified by optical emission spectroscopy. Sterilization experiments were performed. Results show that the device was effective in deactivating E. coli in water over a wide range of initial concentrations ranging from 10(4) to 10(8) CFU/ml. PMID- 21974631 TI - Note: femtosecond laser micromachining of straight and linearly tapered capillary discharge waveguides. AB - Gas-filled capillary discharge waveguides are important structures in laser plasma interaction applications, such as the laser wakefield accelerator. We present the methodology for applying femtosecond laser micromachining in the production of capillary channels (typically 200-300 MUm in diameter and 30-40 mm in length), including the formalism for capillaries with a linearly tapered diameter. The latter is demonstrated to possess a smooth variation in diameter along the length of the capillary (tunable with the micromachining trajectories). This would lead to a longitudinal plasma density gradient in the waveguide that may dramatically improve the laser-plasma interaction efficiency in applications. PMID- 21974632 TI - Note: anti-strong-disturbance signal processing method of vortex flowmeter with two sensors. AB - Some digital signal processing methods have been used to deal with the output signal of vortex flowmeter for extracting the flow rate frequency from the noisy output of vortex flow rate sensor and achieving the measurement of small flow rate. In applications, however, the power of noise is larger than that of flow rate sometimes. These strong disturbances are caused by pipe vibration mostly. Under this condition the previous digital signal processing methods will be unavailable. Therefore, an anti-strong-disturbance solution is studied for the vortex flowmeter with two sensors in this Note. In this solution, two piezoelectric sensors are installed in the vortex probe. One is called the flow rate sensor for measuring both the flow rate and vibration noise, and the other is called the vibration sensor for detecting the vibration noise and sensing the flow rate signal weakly at the same time. An anti-strong-disturbance signal processing method combining the frequency-domain substation algorithm with the frequency-variance calculation algorithm is proposed to identify the flow rate frequency. When the peak number of amplitude spectrum of the flow rate sensor is different from that of the vibration sensor, the frequency-domain subtraction algorithm will be adopted; when the peak number of amplitude spectrum of the flow rate sensor is the same as that of the vibration sensor, the frequency-variance calculation algorithm will be employed. The whole algorithm is implemented in real time by an ultralow power micro control unit (MCU) to meet requirements of process instrumentation. The experimental results show that this method can obtain the flow rate frequency correctly even if the power of the pipe vibration noise is larger than that of the vortex flow rate signal. PMID- 21974633 TI - Note: a high transmission Faraday optical isolator in the 9.2 MUm range. AB - We have fabricated and characterized an n-doped InSb Faraday isolator in the mid IR range (9.2 MUm). A high isolation ratio (31(2) dB) and low insertion loss (1.9(3) dB) are obtained. Temperature dependance is analyzed. Further possible improvements are discussed, including the realization of a two-stage isolator. A similar design can be used to cover a wide wavelength range (lambda ~ 7.5-30 MUm). PMID- 21974634 TI - Note: binding energy scale calibration of electron spectrometers for photoelectron spectroscopy using a single sample. AB - The feasibility of calibrating the binding energy scale for photoelectron spectroscopy using a single sample without sputter cleaning was investigated. By measuring the Fermi level of a Au film with both monochromatic Al Kalpha (hnu = 1486.7 eV) and He Ialpha (hnu = 21.22 eV), the binding energy scale was simply and accurately calibrated. This method is found to yield binding energy values for the Cu 2p(3/2), Ag 3d(5/2), and Au 4f(7/2) peaks that agree with the standard tabulated values defined in International Organization for Standardization 15472 to within +/-0.02 eV. PMID- 21974636 TI - First numerical investigation of a conjecture by N. N. Nekhoroshev about stability in quasi-integrable systems. AB - We investigate numerically a conjecture by N. N. Nekhoroshev about the influence of a geometric property, called steepness, on the long term stability of quasi integrable systems. In a Nekhoroshev's 1977 paper, it is conjectured that, among the steep systems with the same number nu of frequencies, the convex ones are the most stable, and it is suggested to investigate numerically the problem. Following this suggestion, we numerically study and compare the diffusion of the actions in quasi-integrable systems with different steepness properties in a large range of variation of the perturbation parameter E and different dimensions of phase space corresponding to nu = 3 and nu = 4 (nu <= 2 is not significant for the conjecture). For six dimensional maps (nu = 4), our numerical experiments perfectly agree with the Nekhoroshev conjecture: for both convex and non convex cases, the numerically computed diffusion coefficient D of the actions is compatible with an exponential fit, and the convex case is definitely more stable than the steep one. For four dimensional maps (nu = 3), since we find that in the steep case D(E) has large oscillations around an exponential behaviour, the agreement of our numerical experiments with the conjecture is not sharp, and it is found by considering a sup over different initial conditions. PMID- 21974637 TI - How to combine independent data sets for the same quantity. AB - This paper describes a new mathematical method called conflation for consolidating data from independent experiments that measure the same physical quantity. Conflation is easy to calculate and visualize and minimizes the maximum loss in Shannon information in consolidating several independent distributions into a single distribution. A formal mathematical treatment of conflation has recently been published. For the benefit of experimenters wishing to use this technique, in this paper we derive the principal basic properties of conflation in the special case of normally distributed (Gaussian) data. Examples of applications to measurements of the fundamental physical constants and in high energy physics are presented, and the conflation operation is generalized to weighted conflation for cases in which the underlying experiments are not uniformly reliable. PMID- 21974638 TI - Complex networks analysis of obstructive nephropathy data. AB - Congenital obstructive nephropathy (ON) is one of the most frequent nephropathy observed among newborns and children, and the first cause of end-stage renal diseases treated by dialysis or transplantation. This pathology is characterized by the presence of an obstacle in the urinary tract, e.g., stenosis or abnormal implantation of the urethra in the kidney. In spite of important advances, pathological mechanisms are not yet fully understood. In this contribution, the topology of complex networks created upon vectors of features for control and ON subjects is related with the severity of the pathology. Nodes in these networks represent genetic and metabolic profiles, while connections between them indicate an abnormal relation between their expressions. Resulting topologies allow discriminating ON subjects and detecting which genetic or metabolic elements are responsible for the malfunction. PMID- 21974639 TI - Synchronization based system identification of an extended excitable system. AB - A basic state and parameter estimation scheme for an extended excitable system is presented, where time series from a spatial grid of sampling points are used to drive and synchronize corresponding model equations. Model parameters are estimated by minimizing the synchronization error. This estimation scheme is demonstrated using data from generic models of excitable media exhibiting spiral wave dynamics and chaotic spiral break-up that are implemented on a graphics processing unit. PMID- 21974640 TI - Lyapunov exponent diagrams of a 4-dimensional Chua system. AB - We report numerical results on the existence of periodic structures embedded in chaotic and hyperchaotic regions on the Lyapunov exponent diagrams of a 4 dimensional Chua system. The model was obtained from the 3-dimensional Chua system by the introduction of a feedback controller. Both the largest and the second largest Lyapunov exponents were considered in our colorful Lyapunov exponent diagrams, and allowed us to characterize periodic structures and regions of chaos and hyperchaos. The shrimp-shaped periodic structures appear to be malformed on some of Lyapunov exponent diagrams, and they present two different bifurcation scenarios to chaos when passing the boundaries of itself, namely via period-doubling and crisis. Hyperchaos-chaos transition can also be observed on the Lyapunov exponent diagrams for the second largest exponent. PMID- 21974641 TI - Novel vibrational resonance in multistable systems. AB - We investigate the role of multistable states on the occurrence of vibrational resonance in a periodic potential system driven by both a low-frequency and a high-frequency periodic force in both underdamped and overdamped limits. In both cases, when the amplitude of the high-frequency force is varied, the response amplitude at the low-frequency exhibits a series of resonance peaks and approaches a limiting value. Using a theoretical approach, we analyse the mechanism of multiresonance in terms of the resonant frequency and the stability of the equilibrium points of the equation of motion of the slow variable. In the overdamped system, the response amplitude is always higher than in the absence of the high-frequency force. However, in the underdamped system, this happens only if the low-frequency is less than 1. In the underdamped system, the response amplitude is maximum when the equilibrium point around which slow oscillations take place is maximally stable and minimum at the transcritical bifurcation. And in the overdamped system, it is maximum at the transcritical bifurcation and minimum when the associated equilibrium point is maximally stable. When the periodicity of the potential is truncated, the system displays only a few resonance peaks. PMID- 21974642 TI - On decomposing mixed-mode oscillations and their return maps. AB - Alternating patterns of small and large amplitude oscillations occur in a wide variety of physical, chemical, biological, and engineering systems. These mixed mode oscillations (MMOs) are often found in systems with multiple time scales. Previous differential equation modeling and analysis of MMOs have mainly focused on local mechanisms to explain the small oscillations. Numerical continuation studies reported different MMO patterns based on parameter variation. This paper aims at improving the link between local analysis and numerical simulation. Our starting point is a numerical study of a singular return map for the Koper model which is a prototypical example for MMOs, which also relates to local normal form theory. We demonstrate that many MMO patterns can be understood geometrically by approximating the singular maps with affine and quadratic maps. Motivated by our numerical analysis we use abstract affine and quadratic return map models in combination with two local normal forms that generate small oscillations. Using this decomposition approach we can reproduce many classical MMO patterns and effectively decouple bifurcation parameters for local and global parts of the flow. The overall strategy we employ provides an alternative technique for understanding MMOs. PMID- 21974643 TI - A phase-synchronization and random-matrix based approach to multichannel time series analysis with application to epilepsy. AB - We present a general method to analyze multichannel time series that are becoming increasingly common in many areas of science and engineering. Of particular interest is the degree of synchrony among various channels, motivated by the recognition that characterization of synchrony in a system consisting of many interacting components can provide insights into its fundamental dynamics. Often such a system is complex, high-dimensional, nonlinear, nonstationary, and noisy, rendering unlikely complete synchronization in which the dynamical variables from individual components approach each other asymptotically. Nonetheless, a weaker type of synchrony that lasts for a finite amount of time, namely, phase synchronization, can be expected. Our idea is to calculate the average phase synchronization times from all available pairs of channels and then to construct a matrix. Due to nonlinearity and stochasticity, the matrix is effectively random. Moreover, since the diagonal elements of the matrix can be arbitrarily large, the matrix can be singular. To overcome this difficulty, we develop a random-matrix based criterion for proper choosing of the diagonal matrix elements. Monitoring of the eigenvalues and the determinant provides a powerful way to assess changes in synchrony. The method is tested using a prototype nonstationary noisy dynamical system, electroencephalogram (scalp) data from absence seizures for which enhanced cortico-thalamic synchrony is presumed, and electrocorticogram (intracranial) data from subjects having partial seizures with secondary generalization for which enhanced local synchrony is similarly presumed. PMID- 21974644 TI - Stability, bifurcations, and dynamics of global variables of a system of bursting neurons. AB - An approximate mean field model of an ensemble of delayed coupled stochastic Hindmarsh-Rose bursting neurons is constructed and analyzed. Bifurcation analysis of the approximate system is performed using numerical continuation. It is demonstrated that the stability domains in the parameter space of the large exact systems are correctly estimated using the much simpler approximate model. PMID- 21974645 TI - Stability of strategies in payoff-driven evolutionary games on networks. AB - We consider a network of coupled agents playing the Prisoner's Dilemma game, in which players are allowed to pick a strategy in the interval [0, 1], with 0 corresponding to defection, 1 to cooperation, and intermediate values representing mixed strategies in which each player may act as a cooperator or a defector over a large number of interactions with a certain probability. Our model is payoff-driven, i.e., we assume that the level of accumulated payoff at each node is a relevant parameter in the selection of strategies. Also, we consider that each player chooses his/her strategy in a context of limited information. We present a deterministic nonlinear model for the evolution of strategies. We show that the final strategies depend on the network structure and on the choice of the parameters of the game. We find that polarized strategies (pure cooperator/defector states) typically emerge when (i) the network connections are sparse, (ii) the network degree distribution is heterogeneous, (iii) the network is assortative, and surprisingly, (iv) the benefit of cooperation is high. PMID- 21974646 TI - Adaptive mechanism between dynamical synchronization and epidemic behavior on complex networks. AB - Many realistic epidemic networks display statistically synchronous behavior which we will refer to as epidemic synchronization. However, to the best of our knowledge, there has been no theoretical study of epidemic synchronization. In fact, in many cases, synchronization and epidemic behavior can arise simultaneously and interplay adaptively. In this paper, we first construct mathematical models of epidemic synchronization, based on traditional dynamical models on complex networks, by applying the adaptive mechanisms observed in real networks. Then, we study the relationship between the epidemic rate and synchronization stability of these models and, in particular, obtain the conditions of local and global stability for epidemic synchronization. Finally, we perform numerical analysis to verify our theoretical results. This work is the first to draw a theoretical bridge between epidemic transmission and synchronization dynamics and will be beneficial to the study of control and the analysis of the epidemics on complex networks. PMID- 21974647 TI - Cascading failures and the emergence of cooperation in evolutionary-game based models of social and economical networks. AB - We study catastrophic behaviors in large networked systems in the paradigm of evolutionary games by incorporating a realistic "death" or "bankruptcy" mechanism. We find that a cascading bankruptcy process can arise when defection strategies exist and individuals are vulnerable to deficit. Strikingly, we observe that, after the catastrophic cascading process terminates, cooperators are the sole survivors, regardless of the game types and of the connection patterns among individuals as determined by the topology of the underlying network. It is necessary that individuals cooperate with each other to survive the catastrophic failures. Cooperation thus becomes the optimal strategy and absolutely outperforms defection in the game evolution with respect to the "death" mechanism. Our results can be useful for understanding large-scale catastrophe in real-world systems and in particular, they may yield insights into significant social and economical phenomena such as large-scale failures of financial institutions and corporations during an economic recession. PMID- 21974648 TI - Nonlinear vocal fold dynamics resulting from asymmetric fluid loading on a two mass model of speech. AB - Nonlinear vocal fold dynamics arising from asymmetric flow formations within the glottis are investigated using a two-mass model of speech with asymmetric vocal fold tensioning, representative of unilateral vocal fold paralysis. A refined theoretical boundary-layer flow solver is implemented to compute the intraglottal pressures, providing a more realistic description of the flow than the standard one-dimensional, inviscid Bernoulli flow solution. Vocal fold dynamics are investigated for subglottal pressures of 0.6 < p(s) < 1.5 kPa and tension asymmetries of 0.5 < Q < 0.8. As tension asymmetries become pronounced the asymmetric flow incites nonlinear behavior in the vocal fold dynamics at subglottal pressures that are associated with normal speech, behavior that is not captured with standard Bernoulli flow solvers. Regions of bifurcation, coexistence of solutions, and chaos are identified. PMID- 21974649 TI - Generating and enhancing lag synchronization of chaotic systems by white noise. AB - In this paper, we study the crucial impact of white noise on lag synchronous regime in a pair of time-delay unidirectionally coupled systems. Our result demonstrates that merely via white-noise-based coupling lag synchronization could be achieved between the coupled systems (chaotic or not). And it is also demonstrated that a conventional lag synchronous regime can be enhanced by white noise. Sufficient conditions are further proved mathematically for noise-inducing and noise-enhancing lag synchronization, respectively. Additionally, the influence of parameter mismatch on the proposed lag synchronous regime is studied, by which we announce the robustness and validity of the new strategy. Two numerical examples are provided to illustrate the validity and some possible applications of the theoretical result. PMID- 21974650 TI - Stability and chaotification of vibration isolation floating raft systems with time-delayed feedback control. AB - This paper presents a systematic study on the stability of a two-dimensional vibration isolation floating raft system with a time-delayed feedback control. Based on the generalized Sturm criterion, the critical control gain for the delay independent stability region and critical time delays for the stability switches are derived. The critical conditions can provide a theoretical guidance of chaotification design for line spectra reduction. Numerical simulations verify the correctness of the approach. Bifurcation analyses reveal that chaotification is more likely to occur in unstable region defined by these critical conditions, and the stiffness of the floating raft and mass ratio are the sensitive parameters to reduce critical control gain. PMID- 21974651 TI - Transient chaos in optical metamaterials. AB - We investigate the dynamics of light rays in two classes of optical metamaterial systems: (1) time-dependent system with a volcano-shaped, inhomogeneous and isotropic refractive-index distribution, subject to external electromagnetic perturbations and (2) time-independent system consisting of three overlapping or non-overlapping refractive-index distributions. Utilizing a mechanical-optical analogy and coordinate transformation, the wave-propagation problem governed by the Maxwell's equations can be modeled by a set of ordinary differential equations for light rays. We find that transient chaotic dynamics, hyperbolic or nonhyperbolic, are common in optical metamaterial systems. Due to the analogy between light-ray dynamics in metamaterials and the motion of light in matter as described by general relativity, our results reinforce the recent idea that chaos in gravitational systems can be observed and studied in laboratory experiments. PMID- 21974652 TI - Flights in a pseudo-chaotic system. AB - We consider the problem of transport in a one-parameter family of piecewise rotations of the torus, for rotation number approaching 1/4. This is a zero entropy system which in this limit exhibits a divided phase space, with island chains immersed in a "pseudo-chaotic" region. We identify a novel mechanism for long-range transport, namely the adiabatic destruction of accelerator-mode islands. This process originates from the approximate translational invariance of the phase space and leads to long flights of linear motion, for a significant measure of initial conditions. We show that the asymptotic probability distribution of the flight lengths is determined by the geometric properties of a partition of the accelerator-mode island associated with the flight. We establish the existence of flights travelling distances of order O(1) in phase space. We provide evidence for the existence of a scattering process that connects flights travelling in opposite directions. PMID- 21974653 TI - Synchronization in counter-rotating oscillators. AB - An oscillatory system can have opposite senses of rotation, clockwise or anticlockwise. We present a general mathematical description of how to obtain counter-rotating oscillators from the definition of a dynamical system. A type of mixed synchronization emerges in counter-rotating oscillators under diffusive scalar coupling when complete synchronization and antisynchronization coexist in different state variables. We present numerical examples of limit cycle van der Pol oscillator and chaotic Rossler and Lorenz systems. Stability conditions of mixed synchronization are analytically obtained for both Rossler and Lorenz systems. Experimental evidences of counter-rotating limit cycle and chaotic oscillators and mixed synchronization are given in electronic circuits. PMID- 21974654 TI - Pinning control of complex networks via edge snapping. AB - In this paper, we propose a hierarchy of novel decentralized adaptive pinning strategies for controlled synchronization of complex networks. This hierarchy addresses the fundamental need of selecting the sites to pin through a fully decentralized approach based on edge snapping. Specifically, we present three different strategies of increasing complexity which use a combination of network evolution and adaptation of the coupling and control gains. Theoretical results are complemented by extensive numerical investigations of the performance of the proposed strategies on a set of testbed examples. PMID- 21974655 TI - Chaotic solitons in the quadratic-cubic nonlinear Schrodinger equation under nonlinearity management. AB - We analyze the response of rational and regular (hyperbolic-secant) soliton solutions of an extended nonlinear Schrodinger equation (NLSE) which includes an additional self-defocusing quadratic term, to periodic modulations of the coefficient in front of this term. Using the variational approximation (VA) with rational and hyperbolic trial functions, we transform this NLSE into Hamiltonian dynamical systems which give rise to chaotic solutions. The presence of chaos in the variational solutions is corroborated by calculating their power spectra and the correlation dimension of the Poincare maps. This chaotic behavior (predicted by the VA) is not observed in the direct numerical solutions of the NLSE when rational initial conditions are used. The solitary-wave solutions generated by these initial conditions gradually decay under the action of the nonlinearity management. On the contrary, the solutions of the NLSE with exponentially localized initial conditions are robust solitary-waves with oscillations consistent with a chaotic or a complex quasiperiodic behavior. PMID- 21974656 TI - Robust outer synchronization between two complex networks with fractional order dynamics. AB - Synchronization between two coupled complex networks with fractional-order dynamics, hereafter referred to as outer synchronization, is investigated in this work. In particular, we consider two systems consisting of interconnected nodes. The state variables of each node evolve with time according to a set of (possibly nonlinear and chaotic) fractional-order differential equations. One of the networks plays the role of a master system and drives the second network by way of an open-plus-closed-loop (OPCL) scheme. Starting from a simple analysis of the synchronization error and a basic lemma on the eigenvalues of matrices resulting from Kronecker products, we establish various sets of conditions for outer synchronization, i.e., for ensuring that the errors between the state variables of the master and response systems can asymptotically vanish with time. Then, we address the problem of robust outer synchronization, i.e., how to guarantee that the states of the nodes converge to common values when the parameters of the master and response networks are not identical, but present some perturbations. Assuming that these perturbations are bounded, we also find conditions for outer synchronization, this time given in terms of sets of linear matrix inequalities (LMIs). Most of the analytical results in this paper are valid both for fractional-order and integer-order dynamics. The assumptions on the inner (coupling) structure of the networks are mild, involving, at most, symmetry and diffusivity. The analytical results are complemented with numerical examples. In particular, we show examples of generalized and robust outer synchronization for networks whose nodes are governed by fractional-order Lorenz dynamics. PMID- 21974657 TI - Lagrangian coherent structures are associated with fluctuations in airborne microbial populations. AB - Many microorganisms are advected in the lower atmosphere from one habitat to another with scales of motion being hundreds to thousands of kilometers. The concentration of these microbes in the lower atmosphere at a single geographic location can show rapid temporal changes. We used autonomous unmanned aerial vehicles equipped with microbe-sampling devices to collect fungi in the genus Fusarium 100 m above ground level at a single sampling location in Blacksburg, Virginia, USA. Some Fusarium species are important plant and animal pathogens, others saprophytes, and still others are producers of dangerous toxins. We correlated punctuated changes in the concentration of Fusarium to the movement of atmospheric transport barriers identified as finite-time Lyapunov exponent-based Lagrangian coherent structures (LCSs). An analysis of the finite-time Lyapunov exponent field for periods surrounding 73 individual flight collections of Fusarium showed a relationship between punctuated changes in concentrations of Fusarium and the passage times of LCSs, particularly repelling LCSs. This work has implications for understanding the atmospheric transport of invasive microbial species into previously unexposed regions and may contribute to information systems for pest management and disease control in the future. PMID- 21974658 TI - Synchronization of impulsively coupled complex systems with delay. AB - This paper investigates the synchronization of complex systems with delay that are impulsively coupled at discrete instants only. Based on the comparison theorem of impulsive differential system, a distributed impulsive control scheme is proposed to achieve the synchronization for systems with delay. In the control strategy, the influence of all nodes to network synchronization relies on its weight. The proposed control scheme is applied to the chaotic delayed Hopfield neural networks and numerical simulations are presented to demonstrate the effectiveness of the proposed scheme. PMID- 21974659 TI - Intrinsic noise induced resonance in presence of sub-threshold signal in Brusselator. AB - In a system of non-linear chemical reactions called the Brusselator, we show that intrinsic noise can be regulated to drive it to exhibit resonance in the presence of a sub-threshold signal. The phenomena of periodic stochastic resonance and aperiodic stochastic resonance, hitherto studied mostly with extrinsic noise, is demonstrated here to occur with inherent systemic noise using exact stochastic simulation algorithm due to Gillespie. The role of intrinsic noise in a couple of other phenomena is also discussed. PMID- 21974660 TI - Intermittent synchronization in a network of bursting neurons. AB - Synchronized oscillations in networks of inhibitory and excitatory coupled bursting neurons are common in a variety of neural systems from central pattern generators to human brain circuits. One example of the latter is the subcortical network of the basal ganglia, formed by excitatory and inhibitory bursters of the subthalamic nucleus and globus pallidus, involved in motor control and affected in Parkinson's disease. Recent experiments have demonstrated the intermittent nature of the phase-locking of neural activity in this network. Here, we explore one potential mechanism to explain the intermittent phase-locking in a network. We simplify the network to obtain a model of two inhibitory coupled elements and explore its dynamics. We used geometric analysis and singular perturbation methods for dynamical systems to reduce the full model to a simpler set of equations. Mathematical analysis was completed using three slow variables with two different time scales. Intermittently, synchronous oscillations are generated by overlapped spiking which crucially depends on the geometry of the slow phase plane and the interplay between slow variables as well as the strength of synapses. Two slow variables are responsible for the generation of activity patterns with overlapped spiking, and the other slower variable enhances the robustness of an irregular and intermittent activity pattern. While the analyzed network and the explored mechanism of intermittent synchrony appear to be quite generic, the results of this analysis can be used to trace particular values of biophysical parameters (synaptic strength and parameters of calcium dynamics), which are known to be impacted in Parkinson's disease. PMID- 21974661 TI - Failure tolerance of spike phase synchronization in coupled neural networks. AB - Neuronal synchronization plays an important role in the various functionality of nervous system such as binding, cognition, information processing, and computation. In this paper, we investigated how random and intentional failures in the nodes of a network influence its phase synchronization properties. We considered both artificially constructed networks using models such as preferential attachment, Watts-Strogatz, and Erdos-Renyi as well as a number of real neuronal networks. The failure strategy was either random or intentional based on properties of the nodes such as degree, clustering coefficient, betweenness centrality, and vulnerability. Hindmarsh-Rose model was considered as the mathematical model for the individual neurons, and the phase synchronization of the spike trains was monitored as a function of the percentage/number of removed nodes. The numerical simulations were supplemented by considering coupled non-identical Kuramoto oscillators. Failures based on the clustering coefficient, i.e., removing the nodes with high values of the clustering coefficient, had the least effect on the spike synchrony in all of the networks. This was followed by errors where the nodes were removed randomly. However, the behavior of the other three attack strategies was not uniform across the networks, and different strategies were the most influential in different network structure. PMID- 21974662 TI - Generating macroscopic chaos in a network of globally coupled phase oscillators. AB - We consider an infinite network of globally coupled phase oscillators in which the natural frequencies of the oscillators are drawn from a symmetric bimodal distribution. We demonstrate that macroscopic chaos can occur in this system when the coupling strength varies periodically in time. We identify period-doubling cascades to chaos, attractor crises, and horseshoe dynamics for the macroscopic mean field. Based on recent work that clarified the bifurcation structure of the static bimodal Kuramoto system, we qualitatively describe the mechanism for the generation of such complicated behavior in the time varying case. PMID- 21974663 TI - Synchronization of period-doubling oscillations in vascular coupled nephrons. AB - The mechanisms by which the individual functional unit (nephron) of the kidney regulates the incoming blood flow give rise to a number of nonlinear dynamic phenomena, including period-doubling bifurcations and intra-nephron synchronization between two different oscillatory modes. Interaction between the nephrons produces complicated and time-dependent inter-nephron synchronization patterns. In order to understand the processes by which a pair of vascular coupled nephrons synchronize, the paper presents a detailed analysis of the bifurcations that occur at the threshold of synchronization. We show that, besides infinite cascades of saddle-node bifurcations, these transitions involve mutually connected cascades of torus and homoclinic bifurcations. To illustrate the broader range of occurrence of this bifurcation structure for coupled period doubling systems, we show that a similar structure arises in a system of two coupled, non-identical Rossler oscillators. PMID- 21974664 TI - Introduction to focus issue on "randomness, structure, and causality: measures of complexity from theory to applications". AB - We introduce the contributions to this Focus Issue and describe their origin in a recent Santa Fe Institute workshop. PMID- 21974665 TI - Increasing complexity with quantum physics. AB - We argue that complex systems science and the rules of quantum physics are intricately related. We discuss a range of quantum phenomena, such as cryptography, computation and quantum phases, and the rules responsible for their complexity. We identify correlations as a central concept connecting quantum information and complex systems science. We present two examples for the power of correlations: using quantum resources to simulate the correlations of a stochastic process and to implement a classically impossible computational task. PMID- 21974666 TI - A geometric approach to complexity. AB - We develop a geometric approach to complexity based on the principle that complexity requires interactions at different scales of description. Complex systems are more than the sum of their parts of any size and not just more than the sum of their elements. Using information geometry, we therefore analyze the decomposition of a system in terms of an interaction hierarchy. In mathematical terms, we present a theory of complexity measures for finite random fields using the geometric framework of hierarchies of exponential families. Within our framework, previously proposed complexity measures find their natural place and gain a new interpretation. PMID- 21974667 TI - Partial information decomposition as a spatiotemporal filter. AB - Understanding the mechanisms of distributed computation in cellular automata requires techniques for characterizing the emergent structures that underlie information processing in such systems. Recently, techniques from information theory have been brought to bear on this problem. Building on this work, we utilize the new technique of partial information decomposition to show that previous information-theoretic measures can confound distinct sources of information. We then propose a new set of filters and demonstrate that they more cleanly separate out the background domains, particles, and collisions that are typically associated with information storage, transfer, and modification in cellular automata. PMID- 21974668 TI - Excess entropy in natural language: Present state and perspectives. AB - We review recent progress in understanding the meaning of mutual information in natural language. Let us define words in a text as strings that occur sufficiently often. In a few previous papers, we have shown that a power-law distribution for so defined words (a.k.a. Herdan's law) is obeyed if there is a similar power-law growth of (algorithmic) mutual information between adjacent portions of texts of increasing length. Moreover, the power-law growth of information holds if texts describe a complicated infinite (algorithmically) random object in a highly repetitive way, according to an analogous power-law distribution. The described object may be immutable (like a mathematical or physical constant) or may evolve slowly in time (like cultural heritage). Here, we reflect on the respective mathematical results in a less technical way. We also discuss feasibility of deciding to what extent these results apply to the actual human communication. PMID- 21974669 TI - Effective theories for circuits and automata. AB - Abstracting an effective theory from a complicated process is central to the study of complexity. Even when the underlying mechanisms are understood, or at least measurable, the presence of dissipation and irreversibility in biological, computational, and social systems makes the problem harder. Here, we demonstrate the construction of effective theories in the presence of both irreversibility and noise, in a dynamical model with underlying feedback. We use the Krohn-Rhodes theorem to show how the composition of underlying mechanisms can lead to innovations in the emergent effective theory. We show how dissipation and irreversibility fundamentally limit the lifetimes of these emergent structures, even though, on short timescales, the group properties may be enriched compared to their noiseless counterparts. PMID- 21974670 TI - Information symmetries in irreversible processes. AB - We study dynamical reversibility in stationary stochastic processes from an information-theoretic perspective. Extending earlier work on the reversibility of Markov chains, we focus on finitary processes with arbitrarily long conditional correlations. In particular, we examine stationary processes represented or generated by edge-emitting, finite-state hidden Markov models. Surprisingly, we find pervasive temporal asymmetries in the statistics of such stationary processes. As a consequence, the computational resources necessary to generate a process in the forward and reverse temporal directions are generally not the same. In fact, an exhaustive survey indicates that most stationary processes are irreversible. We study the ensuing relations between model topology in different representations, the process's statistical properties, and its reversibility in detail. A process's temporal asymmetry is efficiently captured using two canonical unifilar representations of the generating model, the forward-time and reverse-time epsilon-machines. We analyze example irreversible processes whose epsilon-machine representations change size under time reversal, including one which has a finite number of recurrent causal states in one direction, but an infinite number in the opposite. From the forward-time and reverse-time epsilon machines, we are able to construct a symmetrized, but nonunifilar, generator of a process--the bidirectional machine. Using the bidirectional machine, we show how to directly calculate a process's fundamental information properties, many of which are otherwise only poorly approximated via process samples. The tools we introduce and the insights we offer provide a better understanding of the many facets of reversibility and irreversibility in stochastic processes. PMID- 21974671 TI - Challenges for complexity measures: A perspective from social dynamics and collective social computation. AB - We review an empirically grounded approach to studying the emergence of collective properties from individual interactions in social dynamics. When individual decision-making rules, strategies, can be extracted from the time series data, these can be used to construct adaptive social circuits. Social circuits provide a compact description of collective effects by mapping rules at the individual level to statistical properties of aggregates. This defines a simple form of social computation. We consider the properties that complexity measures would need to have to best capture regularities at different level of analysis, from individual rules to circuits to population statistics. One obvious benefit of using the properties and structure of biological and social systems to guide the development of complexity measures is that it is more likely to produce measures that can be applied to data. Principled but pragmatic measures would allow for a rigorous investigation of the relationship between adaptive features at the micro, meso, and macro scales, a long standing goal of evolutionary theory. A second benefit is that empirically grounded complexity measures would facilitate quantitative comparisons of strategies, circuits, and aggregate properties across social systems. PMID- 21974672 TI - Anatomy of a bit: Information in a time series observation. AB - Appealing to several multivariate information measures--some familiar, some new here--we analyze the information embedded in discrete-valued stochastic time series. We dissect the uncertainty of a single observation to demonstrate how the measures' asymptotic behavior sheds structural and semantic light on the generating process's internal information dynamics. The measures scale with the length of time window, which captures both intensive (rates of growth) and subextensive components. We provide interpretations for the components, developing explicit relationships between them. We also identify the informational component shared between the past and the future that is not contained in a single observation. The existence of this component directly motivates the notion of a process's effective (internal) states and indicates why one must build models. PMID- 21974673 TI - Darwinian demons, evolutionary complexity, and information maximization. AB - Natural selection is shown to be an extended instance of a Maxwell's demon device. A demonic selection principle is introduced that states that organisms cannot exceed the complexity of their selective environment. Thermodynamic constraints on error repair impose a fundamental limit to the rate that information can be transferred from the environment (via the selective demon) to the genome. Evolved mechanisms of learning and inference can overcome this limitation, but remain subject to the same fundamental constraint, such that plastic behaviors cannot exceed the complexity of reward signals. A natural measure of evolutionary complexity is provided by mutual information, and niche construction activity--the organismal contribution to the construction of selection pressures--might in principle lead to its increase, bounded by thermodynamic free energy required for error correction. PMID- 21974674 TI - Natural complexity, computational complexity and depth. AB - Depth is a complexity measure for natural systems of the kind studied in statistical physics and is defined in terms of computational complexity. Depth quantifies the length of the shortest parallel computation required to construct a typical system state or history starting from simple initial conditions. The properties of depth are discussed and it is compared with other complexity measures. Depth can only be large for systems with embedded computation. PMID- 21974675 TI - How hidden are hidden processes? A primer on crypticity and entropy convergence. AB - We investigate a stationary process's crypticity--a measure of the difference between its hidden state information and its observed information--using the causal states of computational mechanics. Here, we motivate crypticity and cryptic order as physically meaningful quantities that monitor how hidden a hidden process is. This is done by recasting previous results on the convergence of block entropy and block-state entropy in a geometric setting, one that is more intuitive and that leads to a number of new results. For example, we connect crypticity to how an observer synchronizes to a process. We show that the block causal-state entropy is a convex function of block length. We give a complete analysis of spin chains. We present a classification scheme that surveys stationary processes in terms of their possible cryptic and Markov orders. We illustrate related entropy convergence behaviors using a new form of foliated information diagram. Finally, along the way, we provide a variety of interpretations of crypticity and cryptic order to establish their naturalness and pervasiveness. This is also a first step in developing applications in spatially extended and network dynamical systems. PMID- 21974676 TI - Computational mechanics of molecular systems: Quantifying high-dimensional dynamics by distribution of Poincare recurrence times. AB - A framework that connects computational mechanics and molecular dynamics has been developed and described. As the key parts of the framework, the problem of symbolising molecular trajectory and the associated interrelation between microscopic phase space variables and macroscopic observables of the molecular system are considered. Following Shalizi and Moore, it is shown that causal states, the constituent parts of the main construct of computational mechanics, the epsilon-machine, define areas of the phase space that are optimal in the sense of transferring information from the micro-variables to the macro observables. We have demonstrated that, based on the decay of their Poincare return times, these areas can be divided into two classes that characterise the separation of the phase space into resonant and chaotic areas. The first class is characterised by predominantly short time returns, typical to quasi-periodic or periodic trajectories. This class includes a countable number of areas corresponding to resonances. The second class includes trajectories with chaotic behaviour characterised by the exponential decay of return times in accordance with the Poincare theorem. PMID- 21974677 TI - Local entropy and structure in a two-dimensional frustrated system. AB - We calculate the local contributions to the Shannon entropy and excess entropy and use these information theoretic measures as quantitative probes of the order arising from quenched disorder in the diluted Ising antiferromagnet on a triangular lattice. When one sublattice is sufficiently diluted, the system undergoes a temperature-driven phase transition, with the other two sublattices developing magnetizations of equal magnitude and opposite sign as the system is cooled.(1) The diluted sublattice has no net magnetization but exhibits spin glass ordering. The distribution of local entropies shows a dramatic broadening at low temperatures; this indicates that the system's total entropy is not shared equally across the lattice. The entropy contributions from some regions exhibit local reentrance, although the entropy of the system decreases monotonically as expected. The average excess entropy shows a sharp peak at the critical temperature, showing that the excess entropy is sensitive to the structural changes that occur as a result of the spin glass ordering. PMID- 21974678 TI - Ergodic parameters and dynamical complexity. AB - Using a cocycle formulation, old and new ergodic parameters beyond the Lyapunov exponent are rigorously characterized. Dynamical Renyi entropies and fluctuations of the local expansion rate are related by a generalization of the Pesin formula. How the ergodic parameters may be used to characterize the complexity of dynamical systems is illustrated by some examples: clustering and synchronization, self-organized criticality and the topological structure of networks. PMID- 21974679 TI - Effects of nanometric roughness on surface properties and fibroblast's initial cytocompatibilities of Ti6Al4V. AB - Titanium alloy (Ti6Al4V) has widespread medical applications because of its excellent biocompatibility. Its biological responses can further be enhanced by polishing and passivation. Unfortunately, preparing titanium alloy samples of nanometric roughness is by far much more difficult than preparing those of micrometric roughness, and numerous investigations on roughness induced effects are all focused on micrometric scales. For the remedy, we investigate, at nanometric scale, the influence of roughness on surface properties and biological responses. Six groups of Ti6Al4V with average roughness (R(a)) values of 2.75 30.34 nm are prepared. The results indicated that nanometric roughness of samples change the wettability and amphoteric OH groups. The contact angles monotonically decrease from 2.75 to 30.34 nm and the rougher surfaces lead to higher wettability. The in vitro cell-culture studies, using Murine NIH-3T3 fibroblasts, showed the spindle-shaped morphology on rougher surface compared to round/spherical morphology on smoother surface. A cytodetacher is employed to quantitatively measure the initial adhesion force of fibroblasts to specimen. The adhesion strength of fibroblasts, ranging from 55 to 193 nN, is significantly influenced by the nanometric roughness while the surface is within the range of 2.75-30.34 nm R(a) roughness, and the adhesion strength appeared stronger for rougher surface. The cell number on the smoother surface is higher than on the rougher surface at 5-day culture. The studies indicated that nanometric roughness would alter the surface properties and further influence cell morphology, adhesion strength, and proliferation. PMID- 21974680 TI - X-ray photoelectron spectroscopy characterization of gold nanoparticles functionalized with amine-terminated alkanethiols. AB - Gold nanoparticles (AuNPs) functionalized with a short chain amine-terminated alkanethiol (HS-(CH(2))(2)NH(2) or C2 NH(2)-thiol) are prepared via a direct synthesis method and then ligand-exchanged with a long chain amine-terminated alkanethiol (HS-(CH(2))(11)NH(2) or C11 NH(2)-thiol). Transmission electron microscopy analysis showed the AuNPs were relatively spherical with a median diameter of 24.2 +/- 4.3 nm. X-ray photoelectron spectroscopy was used to determine surface chemistry of the functionalized and purified AuNPs. The ligand exchange process was monitored within the time range from 30 min to 61 days. By the fourth day of exchange all the C2 NH(2)-thiol molecules had been replaced by C11 NH(2)-thiol molecules. C11 NH(2)-thiol molecules continued to be incorporated into the C11 NH(2) self-assembled monolayer between days 4 and 14 of ligand exchange. As the length of the exchange time increased, the functionalized AuNPs became more stable against aggregation. The samples were purified by a centrifugation and resuspension method. The C2 NH(2) covered AuNPs aggregated immediately when purification was attempted. The C11 NH(2) covered AuNPs could be purified with minimal or no aggregation. Small amounts of unbound thiol (~15%) and oxidized sulfur (~20%) species were detected on the ligand-exchanged AuNPs. Some of the unbound thiol and all of the oxidized sulfur could be removed by treating the functionalized AuNPs with HCl. PMID- 21974681 TI - Optimization of protein patterns for neuronal cell culture applications. AB - In the present study, we fabricated two-component extracellular matrix protein patterned substrates with fibronectin (FN) and laminin (LN) because of our interest in the mechanism of axonal regeneration and injury in the central and peripheral nervous systems. The authors investigated how the patterning order and method of attachment affected the spatial distribution and biological activity of the immobilized proteins. Micro-contact printing (MUCP) techniques in concert with reactive surface chemistry were used to modify glass substrates with one- and two-component films of FN and LN, including micrometer-scale patterns of FN and LN. The composition and spatial distributions of both proteins on the patterned surfaces were characterized by x ray photoelectron spectroscopy, epi fluorescence microscopy, atomic force microscopy, and time-of-flight secondary ion mass spectrometry. The authors also characterized the biological activity of the top-most protein layer in a two-layer protein system as well as the ability of the top-most protein layer to mask the biological activity of an underlying protein layer using a fluorescence-based enzyme-linked immunosorbent assay. The order of protein deposition significantly affected the relative biological activity of the upper-most and underlying immobilized proteins. As a result of these optimization studies, maximum biological activity per surface protein was achieved by first immobilizing FN from solution, followed by MUCP of LN on the FN. Addition of MUCP LN films was able to mask ~84% of the underlying FN activity, whereas MUCP FN films were only able to mask ~27% of the underlying LN activity. PMID- 21974682 TI - Direct assessment of living cell mechanical responses during deformation inside microchannel restrictions. AB - The deformation of suspended cells inside microchannel restrictions mimics passive cell transportation in the blood circulation system of the body. The cells traverse or get stuck in narrow vessels, as, e.g., during the metastasis of tumor cells. In this work, the mechanical responses of suspended pancreatic cancer cells as they move through and deform inside microchannel restrictions are assessed with a cantilever-based polydimethylsiloxane (PDMS) force sensor. Incorporated into a flow cell chip, the PDMS cantilever is integrated into the boundary wall of a narrow microrestriction. Upon being forced to enter the restriction by an applied flow, the cell exerts pressure on the cantilever, which then bends. By assuming a uniformly loaded cantilever, the total force and pressure on the cantilever can be calculated using elastic beam theory. This technique has the advantage of presenting an absolute and direct measure, which is independent of the applied flow and frictional processes at the channel-cell interface; in contrast to, e.g., measuring cell mechanics indirectly via cell sliding velocities. Furthermore, a high number of cells can be examined in a short time compared to other single cell mechanical testing devices. PMID- 21974683 TI - Cosmetic powder suspensions in compliant, fingerprintlike contacts. AB - Cosmetic powders are regularly employed in skin creams and cosmetic formulations to improve performance and enhance skin feel. A previous study investigated the effect of particle concentration and size on the lubricating properties of powder suspensions in smooth, compliant contacts [Timm et al., Tribol. Int. (2011)]. In this paper the tribological properties of cosmetic powder suspensions are investigated in compliant contacts having model fingerprintlike surface topography. Friction coefficients were measured for a series of powder suspensions with varying particle size and concentration in a polydimethylsiloxane (PDMS)/PDMS contact. A commercial tribometer (MTM, PCS Instruments) was employed to measure friction as a function of rubbing time (20 min), under pure sliding (50 mm/s) and low load (0.5 N) conditions. Compared to results using smooth surfaces, it was clear that surface topography has a pronounced affect on the time-dependent tribological behavior of the cosmetic powder suspensions studied. A two-stage friction coefficient versus time curve was observed. By varying the particle size and concentration it was shown that the duration and magnitude of each stage can be controlled. PMID- 21974685 TI - 3-Hydroxy-6,7-dihydropyrimido[2,1-c][1,4]oxazin-4(9H)-ones as new HIV-1 integrase inhibitors WO2011046873 A1. AB - Since the discovery of raltegravir, the first FDA-approved integrase inhibitor, Merck and other pharmaceutical companies have continued their research programs in order to introduce novel molecules as second generation integrase inhibitors. Elvitegravir (Japan Tobacco/Gilead) and dolutegravir (Shionogi/GlaxoSmithKline) are in advanced stages of clinical development. Bristol-Myers Squibb has developed molecules leading to BMS-707035, which was stopped at the Phase II clinical trial stage. Herein is presented the last patent from this company where, in particular, new 3-hydroxy-6,7-dihydropyrimido[2,1-c][1,4]oxazin-4(9H) ones are synthesized and their biological properties given. PMID- 21974684 TI - TOF-SIMS imaging of adsorbed proteins on topographically complex surfaces with Bi(3) (+) primary ions. AB - Although previous studies have demonstrated that TOF-SIMS is a powerful method for the characterization of adsorbed proteins due to its specificity and surface sensitivity, it was unclear from earlier work whether the differences between proteins observed on uniform flat surfaces were large enough to facilitate clear image contrast between similar proteins in small areas on topographically complex samples that are more typical of biological tissues. The goal of this study was to determine whether Bi(3) (+) could provide sufficiently high sensitivity to provide clear identification of the different proteins in an image. In this study, 10 MUm polystyrene microspheres were adsorbed with one of three different proteins, human serum albumin (HSA), bovine serum albumin (BSA), and hemoglobin. Spheres coated with HSA were then mixed with spheres coated with either BSA (a very similar protein) or hemoglobin (a dramatically different protein), and deposited on silicon substrates. Fluorescent labeling was used to verify the SIMS results. With maximum autocorrelation factors (MAF) processing, images showed clear contrast between both the very different proteins (HSA and hemoglobin) and the very similar proteins (HSA and BSA). Similar results were obtained with and without the fluorescent labels. MAF images were calculated using both the full spectrum and only characteristic amino acid fragments. Although better image contrast was obtained using the full spectrum, differences between the spheres were still evident when only the amino acid fragments were included in the analysis, suggesting that we are truly observing differences between the proteins themselves. These results demonstrate that TOF-SIMS, with a Bi(3) (+) primary ion, is a powerful technique for characterizing interfacial proteins not only on large uniform surfaces, but also with high spatial resolution on the topographically complex samples typical in biological analysis. PMID- 21974688 TI - Plastidic isoprenoid biosynthesis in tomato: physiological and molecular analysis in genotypes resistant and sensitive to drought stress. AB - Isoprenoid compounds synthesised in the plastids are involved in plant response to water deficit. The functionality of the biosynthetic pathway of these compounds under drought stress has been analysed at the physiological and molecular levels in two related species of tomato (Solanum chilense and Solanum lycopersicum) that differ in their tolerance to abiotic challenge. Expression analysis of the genes encoding enzymes of these pathways (DXS, IPI, GGPPS, PSY1, NCED and HPT1) in plants at different RWC values shows significant differences for only GGPPS and HPT1, with higher expression in the tolerant S. chilense. Chlorophyll, carotenoids, alpha-tocopherol and ABA content was also determined in both species under different drought conditions. In agreement with HPT1 transcriptional activity, higher alpha-tocopherol content was observed in S. chilense than in S. lycopersicum, which correlates with a lower degree of lipoperoxidation in the former species. These results suggest that, in addition to lower stomatal conductance, alpha-tocopherol biosynthesis is part of the adaptation mechanisms of S. chilense to adverse environmental conditions. PMID- 21974689 TI - In vitro study of the effect of three hydrogen peroxide concentrations on the corrosion behavior and surface topography of alumina-reinforced dental ceramic. AB - PURPOSE: This in vitro investigation studied the effect of three hydrogen peroxide (HP) concentrations (30%, 35%, 38% v/v) at two time intervals (1 and 2 hours) on the corrosion behavior and surface topography of a dental ceramic. MATERIALS AND METHODS: A total of 62 Vitadur Alpha discs were constructed following manufacturer instructions. Specimens were divided into four main groups (n = 8). Group 1 (control): specimens were immersed in 4% acetic acid for 18 hours at 80 degrees C. Groups 2, 3, and 4: specimens were immersed in 30%, 35%, and 38% HP concentrations, respectively. Each of the three groups was divided into two subgroups (a and b) according to the immersion time (1 and 2 hours, respectively). Specimens of subgroup a were further immersed in 4% acetic acid for 18 hours at 80 degrees C and were designated as subgroup c. The corrosion behavior of the ceramic specimens were tested by solution analysis using the atomic absorption method, weight loss percent, and corrosion rate. Surface topography was investigated by surface roughness (Ra) measurements and scanning electron microscopy (SEM). Results were statistically analyzed. RESULTS: There was a significant increase for ions leached with the increase in time of immersion for all ions at 35% and 38% HP, while at 30% HP, ions of K(+) , Al(3+) , and Si(4+) did not increase significantly with time. The results also showed that at a fixed time of immersion, all ions released were dependent on the increase of HP concentration except for Al(3+) ions (p < 0.05). The combined treatment of specimens with HP followed by acetic acid had a significant effect on the increase of ions leached (p < 0.05). The surface roughness values for all specimens increased significantly with time of immersion as well as with the increase in concentration of HP (p < 0.05). These results were confirmed with SEM. CONCLUSIONS: The amount of released ions is directly proportional to HP concentration and time of immersion. Specimens exposed to both HP and acetic acid showed increased weight loss and a higher corrosion rate than those exposed to acetic acid only. Surface roughness values were time and HP concentration dependent. PMID- 21974690 TI - Why does needle photosynthesis decline with tree height in Norway spruce? AB - Needle morphological, chemical and physiological characteristics of Norway spruce were studied in a forest chronosequence in Jarvselja Experimental Forest, Estonia. Current-year shoots were sampled from upper canopy positions in five stands, ranging in height from 1.8 to 33.0 m (corresponding age range was 10-85 years). A/C(i) curves were determined to obtain maximum carboxylation rates (V(cmax)) and maximum rates of electron transport (J(max)). Needle nitrogen (N) partitioning into photosynthetic functions was calculated from the values of V(cmax), J(max) and leaf chlorophyll concentration. All needle size parameters (length, width, thickness, volume and cross-sectional areas of mesophyll and xylem) increased significantly with tree height. The needles of taller trees had lower mass-based N and chlorophyll concentrations (21% and 43% difference between shortest and tallest stands, respectively), but higher dry mass per area (35%), dry mass per volume (18%), number of cells per mesophyll cross-section area (40%) and partitioning of N into non-photosynthetic functions (12%). Light saturated net assimilation rate, V(cmax), J(max) and stomatal conductance decreased with tree age (35%, 16%, 12% and 29% difference, respectively). A path analysis model describing tree age-related reduction of photosynthetic capacity as a result of sink limitation provided the best fit to our data. However, since the path model corresponding to source limitation, where photosynthetic reduction derives from changes in needle structure and chemistry was not rejected, we conclude that the decline in photosynthesis with tree age results from several mechanisms (limited sink strength, stomatal and N limitation) operating simultaneously and sequentially. PMID- 21974691 TI - Using touch-screen technology to assess smoking in a low-income primary care clinic: a pilot study. AB - This pilot study examined the use of a touch-screen tablet personal computer to assess smoking and alcohol use among low-income primary care patients (N = 100) and tested cross-method consistency with a paper assessment. Data were collected in 2009. A touch-screen survey assessed smoking, alcohol use, partner smoking, and acceptability. A separate paper survey assessed smoking, partner smoking, and acceptability. The touch-screen assessment was highly acceptable and reliable. Implications and limitations are noted. Future research should explore the use of touch-screen technology for clinical endeavors requiring a quick assessment of substance use. There was no outside funding for this study. PMID- 21974692 TI - Long-term effectiveness of secondary prevention in geriatric nurses with occupational hand eczema: the challenge of a controlled study design. AB - BACKGROUND: The high prevalence of occupational dermatoses indicates the need for effective and sustainable prevention strategies. OBJECTIVES: To evaluate the long term effectiveness of secondary prevention in geriatric nurses. PATIENTS/METHODS: One hundred and two geriatric nurses with occupational hand eczema participated in an interdisciplinary prevention programme [intervention group (IG)]. Members of the control group (CG) (n = 107) were medically treated by local dermatologists. Six years after intervention (T2), data on job continuation, skin lesions and skin protection behaviour were obtained by standardized questionnaires and compared with baseline values (T0) and data from a 3-month follow-up (T1). RESULTS: At T2, 65.3% of the IG and 56.8% of the CG still worked as geriatric nurses; 6.9% of the IG and 13.6% of the CG had given up work because of occupational hand eczema. The skin status improved in both cohorts. The data indicated a lower frequency of skin lesions and morphological signs in the IG, for example vesicles (IG, 12.8%; CG, 40.0%; chi(2) = 7.00, degrees of freedom = 1, p = 0.008). CONCLUSIONS: The results indicate long-term effects regarding job continuation and disease severity, although few results showed statistical significance. It is outlined that controlled long-term studies aiming at proving the general effectiveness of secondary prevention are no longer feasible in Germany, as the statutory accident insurance has led to a legal entitlement of all patients affected by occupational hand eczema to immediate preventive intervention. PMID- 21974693 TI - Computational insight into the carbenic character of nitrilimines from a reactivity perspective. AB - Nitrilimines (R-CNN-R) can be described through a carbenic valence bond structure, and although intermolecular carbenic reactions from nitrilimines are unknown, intramolecular reaction products from ortho-vinyl MeCOO-CNN-Ph (1) and Ph-CNN-Ph (2) that seem to have followed two typical carbene reaction mechanisms, [1+2] cycloaddition and C-H insertion, have been reported. This study sheds light on whether such reaction mechanisms are tenable, using the electron density and its Laplacian (QTAIM), natural bond orbital (NBO) descriptions, and reaction profiles. It is shown that the reaction in 1 is distinctly different from the [1+2] cycloadditions of ethene with the typical singlet carbene CF(2) and the nitrilimine F-CNN-F with its large carbenic character, and the formal [1+2] cycloaddition product from 1 is in fact not the primary product. Similarly, it is shown that the reaction in 2 is fundamentally different from the C-H insertions of CF(2), F-CNN-F, and even H-CNN-H with its small carbenic character into methane, and again the formal C-H insertion product from 2 is not the primary product. The small model reactions from CF(2), F-CNN-F, and H-CNN-H were analyzed using B3LYP, MP2, and B2PLYP with the aug-cc-pVTZ basis set, whereas the full study was performed with B3LYP/6-31+G(2d,2p), as it was shown to be sufficient. PMID- 21974694 TI - Theoretical basis of pathogenic substance removal during plasmapheresis. AB - This article explains theoretical considerations of prescribing plasmapheresis. It is important to consider several factors in prescribing apheresis: (i) the properties of pathogenic substances, such as molecular weight, distribution volume, compartment, and production rate; (ii) therapeutic conditions such as the processed plasma volume and the frequency of processing; and (iii) the patient's condition, such as active bleeding or infection. A substance's molecular weight determines whether it can be removed using a particular membrane filter. Substances with a small distribution volume and low production rate are removed. Consequently, the processed volume per total plasma volume is related to the single-session efficacy. Nevertheless, even frequent therapy cannot reduce the total pool of a substance within the body if movement from outside the vessels is slow. Active bleeding or infection might be exacerbated by modalities other than simple plasma exchange with fresh plasma supplementation because such therapies cannot replenish substances other than albumin. PMID- 21974695 TI - Positive outcomes of high hemoglobin target in patients with chronic kidney disease not on dialysis: a randomized controlled study. AB - Correcting anemia in patients with chronic kidney disease (CKD) to higher hemoglobin (Hb) levels may be associated with increased risk. No optimal target for Hb has been established. This controlled study examined 321 patients with CKD who were not on dialysis, had a Hb level of <10g/dL, and a serum creatinine of 2.0 to 6.0mg/dL. They were randomized into two target Hb groups: 161 to high Hb (11.0-13.0g/dL) to receive darbepoetin alfa and low Hb to 160 (9.0-11.0g/dL) to receive recombinant erythropoietin. The study lasted 48weeks. Of 154 and 153 patients with adverse events, cardiovascular adverse events developed in 42 and 51 patients in the high and low Hb groups, respectively, with no significant difference in the incidence. All quality of life scores improved in the high Hb group and vitality improved significantly more with high Hb (P=0.025). The left ventricular mass index (LVMI) remained stable in the low Hb group, but there was a significant decrease in LVMI in the high group (P<0.001). There were no safety concerns with targeting a higher Hb level during the 48weeks of this study. Patients with a higher Hb target had comparatively better outcomes with respect to quality of life and LVMI. PMID- 21974696 TI - Serum concentration of complement components of the lectin pathway in maintenance hemodialysis patients, and relatively higher levels of L-Ficolin and MASP-2 in Mannose-binding lectin deficiency. AB - Mannose-binding lectin (MBL), L-ficolin and MBL associated serine protease-2 (MASP-2) are molecules involved in initiation of the lectin pathway (LP) in the complement system. Although MBL deficiency is observed in almost 10% of healthy people, studies of associations between MBL deficiency and end-stage renal disease (ESRD) remain rare. The objective of the present study is to clarify the significance of the LP in maintenance hemodialysis (HD) patients, especially in terms of MBL levels. Two hundred and forty-four HD patients who had been followed up for 74+/-84months and 199 healthy controls were included in this study. Measurements of serum concentrations of MBL, L-ficolin, and MASP-2 were performed. Low serum MBL levels (<0.1ug/mL) in the patients were confirmed by examination of a point mutation in the Mbl-2 gene. Seventeen HD patients (7%) and 20 healthy controls (10%) had MBL deficiency. During the follow-up period, 99 patients died. There was no significant difference in the frequency of deaths by infectious diseases between MBL deficient and non-deficient patients. In both patients and healthy controls with MBL deficiency, the serum concentration of L ficolin tended to be high, and that of MASP-2 was significantly high (P<0.05). MBL deficiency is not a risk factor for HD induction or life-threatening infections. It is postulated that the elevation of concentration of the two components of the LP, L-ficolin and MASP-2, may compensate for the insufficient activity of the LP in MBL deficiency. PMID- 21974697 TI - Outcomes of salvage procedures for occluded autogenous radiocephalic arteriovenous fistula. AB - The outcomes of surgical and endovascular treatments for thrombosed access fistulas are variable and provide no definitive indications for treatment choice. We purposed to review our experience in treating thrombosed radiocephalic arteriovenous fistulas (AVFs) and to evaluate the outcome of procedures, including proximal neo-anastomosis (NEO), replacement of the stenosed segment with a polytetrafluoroethylene graft (GI), patch angioplasty (PA), and endovascular procedures (such as percutaneous transluminal angioplasty [PTA]). A total of 117 occluded radiocephalic AVFs were treated by surgery or an endovascular procedure from January 2002 to December 2007. We evaluated the rates of initial success, re-thrombosis, the post-interventional five-year patency rate, and temporary catheter requirement. Forty-five patients (38.5%) underwent NEO, 32 patients (27.4%) GI, 10 patients (8.5%) PA, and 30 patients (25.6%) PTA. The overall initial procedural success rate was 98.3% (surgery 98.9% and PTA 96.7%), and the post-interventional patency rates at five years were 92.2% (97.1% for NEO, 82.7% for GI, 90.0% for PA, and 96.7% for PTA). Twenty-four patients (20.5%) required a temporary catheter during healing of the functioning segment after treatment: four patients for NEO, 18 patients for GI, two patients for PA, and no patients for PTA (P < 0.001). Both surgery and endovascular treatment gave high rates of initial success and low re-thrombosis rates as salvage treatments for occlusion of radiocephalic AVFs, if treatments were selected according to the length, and location of the stenosis to be corrected. When stenosis of a long segment is suspected, endovascular treatment should be attempted first in order to maintain the functional segment and thereby avoid use of a temporary catheter. PMID- 21974698 TI - Influence of antiplatelet medications on bleeding events in hemodialysis patients. AB - Although antiplatelet medication is used in various situations, including for the prevention of ischemic and thrombotic complications, long-term antiplatelet therapy in hemodialysis patients who are at high risk of bleeding may result in a harmful bleeding tendency. We investigated bleeding events that required the cessation of the use of heparin for hemodialysis in all the hemodialysis patients treated in our clinic. This analysis revealed 111 patients, of whom 52 had been treated with antiplatelet agents (female/male, 15/37; age, 70.4+/-11.3years; number of days of hemodialysis treatment in our clinic, 1073+/-696 [31-2144]days; diabetes mellitus [DM]/non-DM, 29/23), and 59 had not been treated with them (female/male, 17/42; age, 66.7+/-14.0 years; number of days of hemodialysis treatment in our clinic, 917+/-605 [26-2102]days; DM/non-DM, 21/38). During treatment in our clinic, 21 of the 52 patients undergoing antiplatelet therapy experienced a bleeding event (gastrointestinal bleeding 16, brain stem hemorrhage 2, others 3), while 7 of the 59 patients not receiving them had a bleeding event (gastrointestinal bleeding 7) (P<0.001). Of note, diabetic patients on antiplatelet therapy had the highest incidence of bleeding events (13 of 29 patients; 44.8%), followed by non-diabetic patients on antiplatelet therapy (7 of 23 patients; 30.4%), diabetic patients not receiving antiplatelets (3 of 21 patients; 14.3%), and finally non-diabetic patients not on antiplatelets (4 of 38 patients; 10.5%). Among the patients on antiplatelet therapy, no correlations were apparent between bleeding events and the duration of such therapy or the number of agents. In conclusion, antiplatelet medications can induce bleeding events more frequently in hemodialysis patients, especially in those with DM, than in non-hemodialysis patients, and such agents should be given only under prudent consideration of the associated risks and benefits. PMID- 21974699 TI - Comparison of acetate-free citrate hemodialysis and bicarbonate hemodialysis regarding the effect of intra-dialysis hypotension and post-dialysis malaise. AB - Compared with acetate dialysate, bicarbonate dialysate has shown beneficial effects in reducing the morbidity associated with dialysis, but a small amount of acetate in bicarbonate dialysate may evoke hypotension or malaise. Acetate-free citrate hemodialysis (AFHD) may avoid these problems. In 44 hemodialysis patients bicarbonate hemodialysis (BHD) was conducted for three months, followed by a switch to AFHD for three months, and a further switch to bicarbonate hemodialysis (ReBHD). In BHD, AFHD and ReBHD, intra-dialysis hypotension and post-dialysis malaise were determined (hypotension: intra-dialysis systolic blood pressure (SBP) was expressed as a percentage of SBP at the start of hemodialysis, malaise was assessed by a self-reported 0 to 3 scale, 0: absence of malaise, 3: unbearable malaise). Compared with BHD, AFHD patients complained of less malaise but the intra-dialysis blood pressure change did not differ significantly (malaise: BHD 0.73 +/- 0.76 vs. AFHD 0.32 +/- 0.47, P < 0.0001, end hemodialysis SBP: BHD 93.6 +/- 8.9 vs. AFHD 93.8 +/- 10.1, P = NS). After switching to ReBHD from AFHD, the malaise score increased (AFHD 0.32 +/- 0.47 vs. ReBHD 0.77 +/- 0.89, P < 0.0001) and the intra-dialysis blood pressure dropped markedly (end hemodialysis SBP: AFHD 93.8 +/- 10.1 vs. ReBHD 87.3 +/- 10.5, P < 0.0001). Malaise was very severe in five patients who could not continue ReBHD. After ten days under ReBHD, ReBHD was changed to AFHD again in all patients. Although the exact mechanisms are not known, AFHD may be preferable to BHD to prevent hemodialysis-induced hypotension and malaise. PMID- 21974700 TI - Long-term efficacy and safety of the small-sized beta2-microglobulin adsorption column for dialysis-related amyloidosis. AB - Dialysis-related amyloidosis (DRA) is one of the major complications often seen in long-term dialysis patients, and is one of the factors that decreases quality of life. beta2-microglobulin (beta2-m) is considered to be a major pathogenic factor in dialysis-related amyloidosis. The Lixelle adsorbent column, with various capacities, has been developed to adsorb beta2-m from the circulating blood of patients with dialysis-related amyloidosis. Using a minimum type of beta2-m-adsorbing column (Lixelle S-15), we evaluated its therapeutic efficacy and safety in dialysis patients. Seventeen hemodialysis patients with DRA were treated with the S-15 column for one year. Treatment was performed three times a week in this study. During the study period, pinch strength, visual analog scale for joint pain, and activities of daily living were evaluated every three months, and blood sampling was performed every six months. After one year's treatment with the S-15 column, the beta2-m level decreased from 29.3+/-9.6mg/L to 24.7+/ 5.1mg/L (P<0.05), and the high sensitive C-reactive protein level decreased from 2996+/-4380ng/mL to 1292+/-1774ng/mL. After one year of S-15 column use, pinch strength increased from 5.9+/-3.0pounds to 7.2+/-3.2pounds (P<0.05), and the visual analog scale for joint pain and activities of daily living score also improved. Long-term use of the Lixelle S-15 column is safe and effective for improvement of quality of life in chronic dialysis patients. Improvement of chronic inflammation may be one of the mechanisms through which the beneficial effects of the column is effected. PMID- 21974701 TI - Efficacy of separated system continuous venovenous hemofiltration in critical acute kidney injury. AB - Integrated system continuous venovenous hemofiltration (CVVH), the most popularly utilized mode for continuous renal replacement therapy (CRRT), needs a sophisticated and expensive machine that is available only in limited critical care units. Separated system CVVH, which can be simply set up, might be an effectively alternative to CRRT. A one-year prospective observational study regarding the efficacy of separated system CVVH was conducted with 192 critically ill patients with acute kidney injury. All patients underwent separated system CVVH with the pre-dilution mode and a mean CVVH dose of 34.9+/-2.7mL/kg/h. The APACHEII score was 23.2+/-8.4 and the Sequential Organ Failure Assessment score was 12.0+/-4.3. No complications, including air-embolism or circuit clotting, were observed and the survival rate was 32.3%. Separated system CVVH is simple, safe, and efficient and could provide cheaper treatments than the integrated system. It could thus be an effective, alternative treatment for critical acute kidney injury patients when the integrated mode is unavailable. PMID- 21974702 TI - Natural history of mineral and bone disorders after living-donor kidney transplantation: a one-year prospective observational study. AB - Mineral and bone disorders (MBD), including hypercalcemia and hypophosphatemia, are common complications after renal transplantation; however, the natural course of these disorders has not been well documented, and the pathogenesis of persistent post-transplant MBD still remains elusive. This study was carried out to show the natural history of mineral metabolism in recipients after living donor kidney transplantation and also to clarify post-transplant risk factors of persistent hypercalcemia and/or hypophosphatemia at 12months after transplantation. Living-donor kidney transplant recipients (N=34) at Tokyo Women's Medical University were prospectively and consecutively recruited. Parameters of MBD, including intact parathyroid hormone and full-length fibroblast growth factor23, were followed. Serum calcium levels increased until the fourth week post-transplantation, after which it reached a plateau; and serum phosphate decreased substantially at one week post-kidney transplantation, but recovered to the reference level at two months. Fibroblast growth factor23 gradually decreased to comparable levels for renal function, while hyperparathyroidism persisted for 12months after transplantation. Multivariate linear regression analysis revealed that intact parathyroid hormone was the best correlating factor with both hypercalcemia and persistent hypophosphatemia at 12months. This study suggests the need for testing of other interventions used for treatment of hyperparathyroidism which may help to offer better management of MBD after kidney transplantation. PMID- 21974703 TI - Preoperative dialysis for liver transplantation in methylmalonic acidemia. AB - Dialysis immediately before liver transplantation for patients with methylmalonic academia (MMA) with the mut0 mutation is considered to be necessary to reduce plasma methylmalonic acid (MMA) levels and prevent metabolic decompensation for a successful surgical outcome; however, this has not yet been conclusively confirmed. Ten pediatric patients underwent living donor liver transplantation at the National Center for Child Health and Development, Tokyo, Japan. Seven patients received dialysis immediately before surgery, but the three most recent patients did not receive dialysis. We monitored plasma MMA levels and evaluated metabolic status during the perioperative period. Plasma MMA levels of patients who received preoperative dialysis were significantly decreased. However, lactic acidosis developed in two patients during surgery. One of the patients who had decreased renal function suffered from severe lactic acidosis after the transplantation and died on post operative day 44. In the three patients who did not receive preoperative dialysis, high plasma MMA levels persisted, but they did not develop metabolic decompensation. Their plasma MMA levels gradually decreased after transplantation. Our results indicated that reducing MMA with preoperative dialysis does not decrease the risk of metabolic decompensation. We will need to evaluate whether preoperative dialysis is necessary for the success of surgery with more cases in the future. Adequate perioperative glucose infusion and careful lactate monitoring are pivotal for success. PMID- 21974704 TI - Role of plasmapheresis performed in hemodialysis units for the treatment of anti neutrophilic cytoplasmic antibody-associated systemic vasculitides. AB - Anti-neutrophilic cytoplasmic antibody (ANCA) positivity is seen in some systemic necrotizing vasculitides. Wegener's granulomatosis and microscopic polyangiitis are among the ANCA-associated systemic vasculitides (AASV) and mortality is very high when renal failure occurs together with alveolar hemorrhage. The role of plasmapheresis in the treatment of these diseases has been studied retrospectively. Twelve patients with AASV who had plasmapheresis together with immunosuppressive medications have been involved. Primary diseases, immunosuppressive protocols, the number of plasmapheresis sessions, the amount of plasma that has been exchanged, urea and creatinine levels before and after treatment, pulmonary findings, the need for hemodialysis, and the outcome of patients were recorded. The mean age of patients was 52.9 +/- 18.2 years. Wegener's granulomatosis was diagnosed in seven (58.3%) and microscopic polyangiitis in five (41.7%) patients. All patients had pulse cyclophosphamide and methylprednisolone followed by maintenance doses and plasmapheresis. Seven patients had hemodialysis at the beginning, and hemodialysis needed to be continued in three patients. Partial and complete remission was seen in 6 (50%) and 3 (25%) patients, respectively, and pulmonary findings regressed in all patients. End-stage renal disease develops generally in AASV due to rapidly progressive glomerulonephritis causing severe irreversible glomerular damage. The mortality rate rises to 50% in cases of renal failure with diffuse alveolar hemorrhage; therefore, pulse immunosuppressive treatment with plasmapheresis may be life-saving, as shown in our study. PMID- 21974705 TI - Low-density lipoprotein adsorption therapy can restore drug sensitivity for immunosuppressants via inhibitory effects upon MDR-1 gene expression. AB - In two patients with steroid-resistant nephrotic syndrome (SRNS), we investigated the relationship between clinical findings during immunosuppressive therapy and multiple drug resistant gene-1 (MDR-1) expression. MDR-1 was detected by real time polymerase chain reaction (PCR). In a boy who initially developed SRNS at 3years, we observed MDR-1 expression over 3years. Maximal and minimal MDR-1 expression were 90,000 and 7800 copies/ug RNA, respectively. In a 4-year-old boy who initially developed SRNS at 3years, we determined MDR-1 expression over 2years. Maximal and minimal MDR-1 expression were 42,000 and 6900, respectively. MDR-1 evaluation requires determination of MDR-1 expression at several time points in a clinical course. Establishment of a normal expression may be needed for each individual patient. Increasing MDR-1 during remission was followed soon by recurrences, an observation that may be a guide for therapeutic choice. LDL influences a humoral factor involved in MDR-1 expression. Both patients responded to LDL adsorption therapy because of elevated LDL levels. While cyclosporine A therapy gradually decreased MDR-1 expression, LDL adsorption therapy decreased expression sharply. Based on the results of the present study, LDL adsorption therapy could contribute to the amelioration of drug sensitivity for immunosuppressants including corticosteroids via inhibitory effects on MDR-1 expression. PMID- 21974706 TI - Amounts of bile acids and bilirubin removed during single-pass albumin dialysis in patients with liver failure. PMID- 21974707 TI - A case of hemodialysis-associated anaphylaxis or anaphylactoid reaction, which responded successfully to very gradual tapering dose of corticosteroid. PMID- 21974708 TI - Plasmapheresis-refractory thrombotic microangiopathy in a hematopoietic stem cell transplant recipient. PMID- 21974709 TI - Finding of kidney arterial aneurysms in a case of Wegener's granulomatosis. PMID- 21974710 TI - Retraction. "Individualization of nadroparin doses inhemodialyzed patients". PMID- 21974713 TI - Hepatitis B infection and myeloma in developing countries: therapeutic dilemmas. PMID- 21974714 TI - The invisible work with tobacco cessation - strategies among dental hygienists. AB - OBJECTIVE: This study elucidates dental hygienists' experiences of work with tobacco cessation among patients who smoke or use snuff. METHODS: Data were obtained and categorized by interviewing 12 dental hygienists, who worked actively with tobacco cessation interventions. Qualitative content analysis was used for analysis. RESULTS: The latent content was formulated into the core category 'the invisible oral health promotion work'. The informants thought that they had a responsibility to work with tobacco cessation. They perceived the financial system in which they perform the activity as frustrating, because tobacco cessation has no treatment code in the dental care insurance. This was one of several reasons why they had to integrate it in other treatment procedures. The results identified three categories: 'balance in the meeting', 'possibilities and hindrance' and 'procedures'. In the narratives, both positive and negative aspects were displayed. CONCLUSIONS: The financial conditions for tobacco cessation interventions need to be reformed and the activity has to be given a higher priority in the organization of dental care. Practical training in performing tobacco cessation interventions is important during the dental hygiene education; otherwise, tobacco cessation interventions will remain invisible in oral health promotion in the future. PMID- 21974715 TI - Edentulism trends among middle-aged and older adults in the United States: comparison of five racial/ethnic groups. AB - OBJECTIVES: This study examined edentulism trends among adults aged 50 and above in five ethnic groups in the United States: Asians, African Americans, Hispanics, Native Americans, and non-Hispanic Caucasians. METHODS: Data came from the National Health Interview Surveys between 1999 and 2008. Respondents included 616 Native Americans, 2,666 Asians, 15,295 African Americans, 13,068 Hispanics, and 86,755 Caucasians. RESULTS: In 2008, Native Americans had the highest predicated rate of edentulism (23.98%), followed by African Americans (19.39%), Caucasians (16.90%), Asians (14.22%), and Hispanics (14.18%). Overall, there was a significant downward trend in edentulism rates between 1999 and 2008 (OR = 0.97, 95% CI: 0.96, 0.98). However, compared with Caucasians, Native Americans showed a significantly less decline of edentulism during this period (OR = 1.10, 95% CI: 1.02, 1.19). CONCLUSIONS: While there was a downward trend in edentulism between 1999 and 2008, significant variations existed across racial/ethnic groups. Innovative public health programs and services are essential to prevent oral health diseases and conditions for minority populations who lack access to adequate dental care. Additionally, given the increasing numbers of adults retaining their natural teeth, interventions designed to assist individuals in maintaining healthy teeth becomes more critical. PMID- 21974716 TI - NMR detection of pH-dependent histidine-water proton exchange reveals the conduction mechanism of a transmembrane proton channel. AB - The acid-activated proton channel formed by the influenza M2 protein is important for the life cycle of the virus. A single histidine, His37, in the M2 transmembrane domain (M2TM) is responsible for pH activation and proton selectivity of the channel. Recent studies suggested three models for how His37 mediates proton transport: a shuttle mechanism involving His37 protonation and deprotonation, a H-bonded imidazole-imidazolium dimer model, and a transporter model involving large protein conformational changes in synchrony with proton conduction. Using magic-angle-spinning (MAS) solid-state NMR spectroscopy, we examined the proton exchange and backbone conformational dynamics of M2TM in a virus-envelope-mimetic membrane. At physiological temperature and pH, (15)N NMR spectra show fast exchange of the imidazole (15)N between protonated and unprotonated states. To quantify the proton exchange rates, we measured the (15)N T(2) relaxation times and simulated them for chemical-shift exchange and fluctuating N-H dipolar fields under (1)H decoupling and MAS. The exchange rate is 4.5 * 10(5) s(-1) for Ndelta1 and 1.0 * 10(5) s(-1) for Nepsilon2, which are approximately synchronized with the recently reported imidazole reorientation. Binding of the antiviral drug amantadine suppressed both proton exchange and ring motion, thus interfering with the proton transfer mechanism. By measuring the relative concentrations of neutral and cationic His as a function of pH, we determined the four pK(a) values of the His37 tetrad in the viral membrane. Fitting the proton current curve using the charge-state populations from these pK(a)'s, we obtained the relative conductance of the five charge states, which showed that the +3 channel has the highest time-averaged unitary conductance. At physiologically relevant pH, 2D correlation spectra indicated that the neutral and cationic histidines do not have close contacts, ruling out the H-bonded dimer model. Moreover, a narrowly distributed nonideal helical structure coexists with a broadly distributed ideal helical conformation without interchange on the sub 10 ms time scale, thus excluding the transporter model in the viral membrane. These data support the shuttle mechanism of proton conduction, whose essential steps involve His-water proton exchange facilitated by imidazole ring reorientations. PMID- 21974717 TI - Direct observation of vibrational energy flow in cytochrome c. AB - Vibrational energy flow in ferric cytochrome c has been examined by picosecond time-resolved anti-Stokes ultraviolet resonance Raman (UVRR) measurements. By taking advantage of the extremely short nonradiative excited state lifetime of heme in the protein (<< ps), excess vibrational energy of 20000-25000 cm(-1) was optically deposited selectively at the heme site. Subsequent energy relaxation in the protein moiety was investigated by monitoring the anti-Stokes UVRR intensities of the Trp59 residue, which is a single tryptophan residue involved in the protein that is located close to the heme group. It was found from temporal changes of the anti-Stokes UVRR intensities that the energy flow from the heme to Trp59 and the energy release from Trp59 took place with the time constants of 1-3 and ~8 ps, respectively. These data are consistent with the time constants for the vibrational relaxation of the heme and heating of water reported for hemeproteins. The kinetics of the energy flow were not affected by the amount of excess energy deposited at the heme group. These results demonstrate that the present technique is a powerful tool for studying the vibrational energy flow in proteins. PMID- 21974718 TI - Genetic relationships of Edwardsiella strains isolated in China aquaculture revealed by rep-PCR genomic fingerprinting and investigation of Edwardsiella virulence genes. AB - AIMS: The aim of this study was to classify Edwardsiella strains isolated from China aquaculture based on biochemical and molecular methods. METHODS AND RESULTS: In this study, biochemical characterization of 19 Edwardsiella tarda isolates and two Edwardsiella ictaluri isolates was performed with API 20E system. Other pathogenicity-related phenotypes such as haemagglutination, haemolytic activities and lethality to fish were also examined in these strains. As it was difficult to categorize the subgroups of Edw. tarda according to their origins or phenotypic properties, three PCR-based methods, i.e. PCR amplification of virulence genes, Enterobacterial repetitive intergenic consensus-PCR and BOX PCR, were carried out to further resolve the relatedness of the Edw. tarda isolates. As a result, all Edw. tarda isolates could be generally grouped into pathogenic and nonpathogenic branches before being classified into strain specific or origin-specific clades. CONCLUSIONS: Biochemical characterization was sensitive for interspecific typing, while PCR-based approaches permitted a more accurate discrimination for intraspecific typing resulting in pathogenic and nonpathogenic clusters and further more delicate clades for Edwardsiella. SIGNIFICANCE AND IMPACT OF THE STUDY: PCR-based genomic fingerprinting to study the relatedness and trace the pathogenicity of the Edwardsiella strains will be helpful in investigating the virulence factors of Edwardsiella and in the development of vaccines and diagnostics for edwardsiellosis. PMID- 21974719 TI - Inheritance of moyamoya disease in a Caucasian family. AB - BACKGROUND AND PURPOSE: Moyamoya disease is a very rare occlusive cerebrovascular disorder characterized by progressive stenosis or occlusion of the intracranial portion of the internal carotid artery and proximal cerebral arteries with an extensive network of fine collaterals. The aetiology and genetic susceptibility of moyamoya disease, especially in Caucasians, still remains unclear. METHODS AND RESULTS: We describe the cases of affected German father, daughter and son with juvenile stroke because of idiopathic moyamoya disease. The rare existing literature is reviewed and discussed. CONCLUSIONS: This is the first report on a father-to-child inheritance pattern in Caucasian patients with idiopathic Moyamoya disease (MMD). Our cases indicate possible genetic risk factors for the genesis of Caucasian Moyamoya disease. PMID- 21974721 TI - Transgenic expression of polygalacturonase-inhibiting proteins in Arabidopsis and wheat increases resistance to the flower pathogen Fusarium graminearum. AB - Fusarium head blight (FHB), caused by Fusarium graminearum, is one of the most important diseases of wheat worldwide, resulting in yield losses and mycotoxin contamination. The molecular mechanisms regulating Fusarium penetration and infection are poorly understood. Beside mycotoxin production, cell wall degradation may play a role in the development of FHB. Many fungal pathogens secrete polygalacturonases (PGs) during the early stages of infection, and plants have evolved polygalacturonase-inhibiting proteins (PGIPs) to restrict pectin degradation during fungal infection. To investigate the role of plant PGIPs in restricting the development of FHB symptoms, we first used Arabidopsis thaliana, whose genome encodes two PGIPs (AtPGIP1 and AtPGIP2). Arabidopsis transgenic plants expressing either of these PGIPs under control of the CaMV 35S promoter accumulate inhibitory activity against F. graminearum PG in their inflorescences, and show increased resistance to FHB. Second, transgenic wheat plants expressing the bean PvPGIP2 in their flowers also had a significant reduction of symptoms when infected with F. graminearum. Our data suggest that PGs likely play a role in F. graminearum infection of floral tissues, and that PGIPs incorporated into wheat may be important for increased resistance to FHB. PMID- 21974720 TI - Finite element modelling of squirrel, guinea pig and rat skulls: using geometric morphometrics to assess sensitivity. AB - Rodents are defined by a uniquely specialized dentition and a highly complex arrangement of jaw-closing muscles. Finite element analysis (FEA) is an ideal technique to investigate the biomechanical implications of these specializations, but it is essential to understand fully the degree of influence of the different input parameters of the FE model to have confidence in the model's predictions. This study evaluates the sensitivity of FE models of rodent crania to elastic properties of the materials, loading direction, and the location and orientation of the models' constraints. Three FE models were constructed of squirrel, guinea pig and rat skulls. Each was loaded to simulate biting on the incisors, and the first and the third molars, with the angle of the incisal bite varied over a range of 45 degrees . The Young's moduli of the bone and teeth components were varied between limits defined by findings from our own and previously published tests of material properties. Geometric morphometrics (GMM) was used to analyse the resulting skull deformations. Bone stiffness was found to have the strongest influence on the results in all three rodents, followed by bite position, and then bite angle and muscle orientation. Tooth material properties were shown to have little effect on the deformation of the skull. The effect of bite position varied between species, with the mesiodistal position of the biting tooth being most important in squirrels and guinea pigs, whereas bilateral vs. unilateral biting had the greatest influence in rats. A GMM analysis of isolated incisor deformations showed that, for all rodents, bite angle is the most important parameter, followed by elastic properties of the tooth. The results here elucidate which input parameters are most important when defining the FE models, but also provide interesting glimpses of the biomechanical differences between the three skulls, which will be fully explored in future publications. PMID- 21974722 TI - Evolution of the YABBY gene family with emphasis on the basal eudicot Eschscholzia californica (Papaveraceae). AB - YABBY genes are seed plant-specific transcriptional regulators that are involved in diverse aspects of leaf, shoot and flower development. A series of duplications gave rise to five gene groups found throughout flowering plants. In Arabidopsis and other species, expression of two gene groups, CRABS CLAW and INNER NO OUTER, is restricted to floral organs. In contrast, members of the FILAMENTOUS FLOWER, YABBY2 and YABBY5 gene groups are also expressed in leaves and have been termed 'vegetative YABBYs'. How the five paralogue groups evolved and how their expression and function diversified have remained largely unresolved, precluding a reconstruction of the natural history of this gene family. Here, we report new genes from Eschscholzia californica (Ranunculales, Papaveraceae) that we use together with currently available database sequences in a comprehensive phylogenetic re-evaluation of the YABBY gene family. Multilayered Bayesian analysis covering seed plants allowed us to locate Eschscholzia YABBY sequences within the gene family phylogeny. We established that vegetative YABBYs do not form a monophyletic clade, and that CRABS CLAW and FILAMENTOUS FLOWER arose from a common ancestor gene. INNER NO OUTER genes are sister to that ancestral gene. We identified several conserved motifs outside of known amino acid domains that define all five angiosperm YABBY gene clades. Further, we inferred the evolution of gene expression and provide evidence for release of purifying constraint in certain branches of the gene family tree. Finally, we report expression patterns for five Eschscholzia YABBY genes consistent with functional conservation between early-diverged and core eudicots. PMID- 21974723 TI - Cooperative spin transition in the two-dimensional coordination polymer [Fe(4,4' bipyridine)2(NCX)2].4CHCl3 (X = S, Se). AB - Two new isostructural two-dimensional (2D) coordination polymers exhibiting spin crossover (SCO) behavior of formulation [Fe(4,4'-bipy)(2)(NCX)(2)].4CHCl(3) (4,4' bipy = 4,4'-bipyridine; X = S [1.4CHCl(3)], Se [2.4CHCl(3)]) have been synthesized and characterized, and both undergo cooperative spin transitions (ST). For 1.4CHCl(3) the ST takes place in two steps with critical temperatures of T(c1)(down) = 143.1 K, T(c2)(down) = 91.2 K, T(c1)(up) = 150.7 K, and T(c2)(up) = 112.2 K. 2.4CHCl(3) displays half ST characterized by T(c)(down) = 161.7 K and T(c)(up) = 168.3 K. The average enthalpy and entropy variations and cooperativity parameters associated with the ST have been estimated to be DeltaH(1)(av) = 5.18 kJ mol(-1), DeltaS(1)(av) = 35 J K(-1) mol(-1), and Gamma(1) = 2.8 kJ mol(-1) and DeltaH(2)(av) = 3.55 kJ mol(-1), DeltaS(2)(av) = 35 J K(-1) mol(-1), and Gamma(2) = 2.6 kJ mol(-1) for 1.4CHCl(3), and DeltaH(av) = 6.25 kJ mol(-1), DeltaS(av) = 38.1 J K(-1) mol(-1), and Gamma = 3.2 kJ mol(-1) for 2.4CHCl(3). At T > [T(c1) (1.4CHCl(3)); T(c) (2.4CHCl(3))], both compounds are in the space group P2/c while at T < [T(c1) (1.4CHCl(3)); T(c) (2.4CHCl(3))] they change to the C2/c space group and display an ordered checkerboard-like arrangement of iron(II) sites where the high- and low-spin states coexist at 50%. PMID- 21974724 TI - Editorial: scientific rigor as the guiding heuristic for SLTB's editorial stance. PMID- 21974725 TI - Transepithelial, Topography-guided Ablation in the Treatment of Visual Disturbances in LASIK Flap or Interface Complications. AB - PURPOSE: To evaluate the efficacy and safety of a single-step, transepithelial, topography-guided surface ablation in the treatment of visual disturbances including irregular astigmatism and light scattering caused by LASIK flap or interface complications. METHODS: Seventeen eyes of 16 patients with LASIK flap or interface complications and central residual stromal thickness >=300 MUm were treated with a topography-guided custom transepithelial "no touch" (cTEN) technique using the iVIS Suite 1-kHz excimer laser (iVIS Technology). Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refraction, corneal irregularity, ocular higher order aberrations (HOAs), and visual symptoms were analyzed. RESULTS: Mean 15.9+/-11.0 months after surgery, mean UDVA improved from 20/87 to 20/25. Mean CDVA improved from 20/28 to 20/19 (P<.001), with 64.7% of eyes gaining two or more lines of CDVA. Mean corneal irregularity index decreased from 25.82 to 20.36 MUm (P=.009). Mean root-mean square (RMS) of total HOAs decreased from 1.30 to 0.49 (P=.042), whereas RMS of the odd-order (3rd and 5th) and even-order (4th and 6th) HOAs decreased from 0.85 to 0.38 (P=.001) and 0.43 to 0.24 (P=.036), respectively. All patients claimed their visual symptoms were better (8 eyes) or cured (9 eyes). CONCLUSIONS: Corneal regularization and removal of the underlying flap or interface pathology by cTEN ablation appears to be an effective treatment for LASIK flap or interface complications associated with visually disturbing irregular astigmatism and light scattering in cases with sufficient residual stromal thickness. PMID- 21974726 TI - Pilomatricoma coexistent with epidermal cyst. PMID- 21974727 TI - A dual regulatory role of Arabidopsis calreticulin-2 in plant innate immunity. AB - Calreticulin (CRT) is an endoplasmic reticulum-resident calcium-binding molecular chaperone that is highly conserved in multi-cellular eukaryotes. Higher plants contain two distinct groups of CRTs: CRT1/CRT2 and CRT3 isoforms. Previous studies have shown that bacterial elongation factor Tu receptor (EFR), a pattern recognition receptor that is responsible for pathogen-associated molecular pattern-triggered immunity, is a substrate for Arabidopsis CRT3, suggesting a role for CRT3 in regulating plant defense against pathogens. Here we report that Arabidopsis CRT2 is another regulator of plant innate immunity. Despite significantly increased salicylic acid levels and constitutive expression of the systemic acquired resistance-associated marker genes PR1, PR2 and PR5, transgenic plants over-expressing CRT2 displayed reduced resistance to virulent Pseudomonas syringae pv. tomato DC3000 (PstDC3000). A (45)Ca(2+) overlay assay and a domain swapping experiment further demonstrated that the negatively charged C-terminal tail of CRT2 is responsible for its high calcium-binding capacity and function in regulating the endogenous salicylic acid level. In addition, over-expression of the His173 mutant of CRT2 greatly enhanced plant defense against PstDC3000, supporting the existence of a self-inhibition mechanism that can counteract the effects of salicylic acid-dependent immune responses. These results suggest that CRT2 functions through its N-terminal domain(s) as a self-modulator that can possibly prevent the salicylic acid-mediated runaway defense responses triggered by its C-terminal calcium-buffering activity in response to pathogen invasion. PMID- 21974728 TI - Risk communication and worry about breast cancer. AB - Feedback concerning breast cancer risk was provided to 59 college-aged women who were overestimating their personal risk. In a 2 (Absolute Risk Feedback; yes or no) * 2 (Comparative Risk Feedback; yes or no) design, women completed a brief risk questionnaire and then received both, one, or neither kind of risk feedback. Absolute information reduced estimates of vulnerability, although not to the levels suggested by the feedback. Absolute feedback had no effect on worry about breast cancer, but worry was lower for women who learned that they were no more at risk than other, similar women. PMID- 21974729 TI - The effect of order of presentation of verbal probability expressions on numerical estimates in a medical context. AB - Many medical decisions are made on a probability estimate. Models of risk benefit calculations in health behaviour rarely articulate how people perceive and appraise such probability. Cognitive processes may mediate the processing of probability expressions and may be important to understand the meaning or the range of meanings that probability statements portray to patients. Past studies have indicated that verbal expressions of probability are vague and subject to individual interpretation. On the theoretical level when subjects are asked to translate a set of verbal probability expressions, ranging from high to low, into their equivalent numerical expressions subjects usually produce a continuum of numerical equivalents also ranging from high to low. In practice clinicians frequently communicate information about uncertainty to the patients by verbal probability estimates. This study explored the effect of the order of presentation of the verbal expressions on the numerical probabilities produced by a group of medical students (n = 87) in relation to medical probabilities. The results showed that the order of presentation (descending vs. random) of the verbal probability expressions was found to have a significant effect on three of the seven numerical probabilities produced by the subjects. The order effect is discussed to together with implications for clinical practice. PMID- 21974730 TI - Changes in psychological well-being in female patients with clinically diagnosed depression: an exploratory approach in a therapeutic setting. AB - The objective of this exploratory one-group pretest-posttest study was to evaluate the nature of psychological change in inward depressed psychiatric patients attending multi-disciplinary treatment, including physical activity, designed to improve mental well-being. Female depressed psychiatric patients (n = 51) were examined before and after this programme over a period of 3 months. The following psychological parameters were assessed: depression, anxiety, global self-esteem, and physical self-perceptions. Depressed patients demonstrated statistically significant improvements in depression, anxiety, global self-esteem and physical self-worth (t(50) ranging from -3.76 to 4.65, all p < 0.007; ES ranging from 0.53 to -0.65). Changes in depression and anxiety displayed a strong negative correlation with changes in global self-esteem, and those changes are independent of the initial severity of the depressive symptoms ( F(2,48) ranging from 0.03 to 0.70, n.s.). Patients with greater improvement in physical self perceptions reported greater improvement anxious symptoms then patients who did not improve. Consequently, within the limitations of the research design it can be concluded that the programme appeared successful in improving psychological well-being in female depressed patients. Results also provide preliminary insight into the potential role of the physical self in recovery. PMID- 21974731 TI - People don't exercise because they can't think of reasons to exercise: an examination of causal reasoning within the Transtheoretical Model. AB - This study compared the accessibility of the pros (advantages) and cons (disadvantages) of exercise in a group of non-exercisers and regular exercisers, using the Transtheoretical Model of behaviour change as a theoretical framework. Pre-contemplators (n = 18), and maintainers (n = 25), were asked to generate a list of 'advantages to taking part in exercise' (pro reasons), and a list of 'disadvantages to taking part in exercise' (con reasons). The time to generate their first item was recorded as well as the total number of items generated within 60 s. The results showed that pre-contemplators provided more con reasons relative to pro reasons; and maintainers provided more pro reasons relative to con reasons for exercise. Pre-contemplators were also quicker to provide their first con reason, relative to their first pro reason, but there was no difference in pro and con latencies in the maintainers. It was concluded that one reason pre contemplation individuals do not participate in regular exercise may be because they cannot think of reasons to exercise. PMID- 21974732 TI - Causal attributions and blame: associations with mothers' adjustment to the birth of a child with Down syndrome. AB - The main purpose of this study is to explore the associations between causal attributions to others, blaming others and mothers' adjustment to the birth of a child with Down syndrome (DS). Participants (n = 214) rated causal attributions to others and blaming others, and completed five measures of adjustment: anger, anxiety, depression, parenting stress, and attitudes towards the child. The adjustment of three groups of mothers was compared: (i) those who made no attributions to others (ii) those who made causal attributions but did not blame, and (iii) those who blamed others. Four years after the births of their children with DS, 16% of mothers blamed others and 17% made causal attributions but did not blame others for this outcome. Those who blamed others had higher levels of anger, anxiety, depression, parenting stress and more negative attitudes towards their children with DS than did those who made causal attributions but did not blame, and those who made who made no attributions to others. The adjustment of the latter two groups did not differ. Investigating blame rather than causal attributions may be a more fruitful area for future research aimed at understanding and facilitating adjustment to illness and other negative life events. PMID- 21974733 TI - An investigation into the psychometric properties of the Hospital Anxiety and Depression Scale in individuals with chronic fatigue syndrome. AB - The study sought to determine the psychometric properties of the Hospital Anxiety and Depression Scale (HADS) in individuals with chronic fatigue syndrome (CFS) assessed using a web-based data collection tool. Exploratory and confirmatory factor analyses were conducted on the HADS to determine its psychometric properties in 117 individuals with CFS. Seven models were tested to determine model fit to the data. Internal reliability estimations of the anxiety and depression sub-scales were found to be acceptable, however, a three-factor model was found to provide a significantly better fit to the data when compared to the bi-dimensional two-factor structure previously assumed to underpin the HADS' construct validity. The clinical utility of the HADS in the assessment of anxiety and depression in CFS appears to be fundamentally compromised by the presence of a three-dimensional underlying factor structure. Future revision of the HADS is recommended if the instrument is to be used reliably to screen CFS patients. PMID- 21974734 TI - Immediate breast reconstruction and psychological adjustment in women who have undergone surgery for breast cancer: a preliminary study. AB - Current debate exists regarding the timing of reconstructive surgery following mastectomy for breast cancer, with research pointing in favour of immediate reconstruction. This cross-sectional study sought to compare the psychological outcome of breast cancer treatment in women who had either received mastectomy and immediate reconstruction using autogenous tissue (n = 30), or mastectomy alone (n = 34), and also determine adjustment factors in this population as a whole. Participants completed measures of depression, anxiety, body image, self esteem, coping and perceived social support at a time point 3 - 15 months after initial surgery. No significant differences were revealed between the two groups on any of the outcome measures. Poor body image, low self-esteem, and a tendency to use coping strategies characterized by helpless/hopelessness and anxious preoccupation, rather than fighting spirit, were highly predictive of distress. Reasons for the lack of differences between the two groups are explored. PMID- 21974735 TI - Intentional and unintentional nonadherence in patients prescribed HAART treatment regimens. AB - The objective was to investigate intentional and unintentional nonadherence to anti-HIV treatment regimens from a decision-making perspective. The participants (n = 117) being treated with anti-HIV medication completed a questionnaire asking about nonadherence; reasons for and against taking the medication; and medical consultation style. Thirty-three participants (29%) reported intentionally missing or altering doses of medication at least 5% of the time; 59 participants (50%) reported forgetting to take medication at least 5% of the time. Intentional nonadherence was associated with the balance of the perceived benefits and losses of taking medication, and extent to which participants were 'prepared for the effects of the medication'. Unintentional nonadherence was associated with demographic and clinical variables. The research highlights the importance of (i) treating intentional and unintentional nonadherence as separate entities; (ii) assessing individuals' idiosyncratic beliefs and internal logic when considering intentional nonadherence; and (iii) ensuring that individuals feel prepared for the effects of their medications. PMID- 21974736 TI - Are exercise social-cognitive factors and behaviours different for adults with diabetes? A randomized community sample. AB - Exercise plays a key role in the prevention and delay of the onset of Type 2 diabetes and in the management of this disorder. To determine if there are differences in key social-cognitive determinants of exercise and self-reported physical activity levels between adults with diabetes and those without the condition, a random selected sample of adults was surveyed. A telephone interview assessed physical activity behaviour and key social-cognitive constructs from major health behaviour change theories/models. The mean energy expenditure was not significantly different between the diabetes (n = 46) and the non-diabetes (n = 1556) groups. The diabetes group reported significantly lower scores for self efficacy and perceived behavioural control, but higher for fear of, and vulnerability to, general health and cardiovascular disease threat. The data suggest that it may not be necessary to promote health threat messages, as threat is already high for this diabetes population and studies have shown that excess threat does not promote recommended exercise and health behaviours. Instead, the low levels of self-efficacy and perceived behavioural control among those with diabetes emphasize the importance of designing specific strategies (e.g., skills, incremental success) to increase their self-confidence in undertaking physical activity. PMID- 21974737 TI - Gender, ethnicity, and health research. PMID- 21974738 TI - 3,4,4'-Trihydroxy-trans-stilbene, an analogue of resveratrol, is a potent antioxidant and cytotoxic agent. AB - Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a naturally occurring polyphenol widely distributed in food and dietary plants. This phytochemical has been intensively studied as an efficient antioxidant and anticancer agent, and a variety of substituted stilbenes have been developed in order to improve the potency of resveratrol. In this work, we described the synthesis of 3,4,4 trihydroxy-trans-stilbene (3,4,4'-THS), an analogue of resveratrol, and studied its antioxidant and cytotoxic activity in vitro. 3,4,4 -THS was much more efficient than resveratrol in protecting against free radical-induced lipid peroxidation, photo-sensitized DNA oxidative damage, and free radical-induced hemolysis of human red blood cells. More potent growth inhibition in cultured human leukemia cells (HL-60) was also observed for 3,4,4 -THS. The relationship between the antioxidant efficiency and cytotoxic activity was discussed, with the emphasis on inhibition of the free radical enzyme ribonucleotide reductase by antioxidants. The result that this subtle structure modification of resveratrol drastically improves its bioactivity provides important strategy to develop novel resveratrol-based molecules. PMID- 21974740 TI - Female sexual function index (FSFI) does not assess female sexual function. PMID- 21974739 TI - New resources for functional analysis of omics data for the genus Aspergillus. AB - BACKGROUND: Detailed and comprehensive genome annotation can be considered a prerequisite for effective analysis and interpretation of omics data. As such, Gene Ontology (GO) annotation has become a well accepted framework for functional annotation. The genus Aspergillus comprises fungal species that are important model organisms, plant and human pathogens as well as industrial workhorses. However, GO annotation based on both computational predictions and extended manual curation has so far only been available for one of its species, namely A. nidulans. RESULTS: Based on protein homology, we mapped 97% of the 3,498 GO annotated A. nidulans genes to at least one of seven other Aspergillus species: A. niger, A. fumigatus, A. flavus, A. clavatus, A. terreus, A. oryzae and Neosartorya fischeri. GO annotation files compatible with diverse publicly available tools have been generated and deposited online. To further improve their accessibility, we developed a web application for GO enrichment analysis named FetGOat and integrated GO annotations for all Aspergillus species with public genome sequences. Both the annotation files and the web application FetGOat are accessible via the Broad Institute's website (http://www.broadinstitute.org/fetgoat/index.html). To demonstrate the value of those new resources for functional analysis of omics data for the genus Aspergillus, we performed two case studies analyzing microarray data recently published for A. nidulans, A. niger and A. oryzae. CONCLUSIONS: We mapped A. nidulans GO annotation to seven other Aspergilli. By depositing the newly mapped GO annotation online as well as integrating it into the web tool FetGOat, we provide new, valuable and easily accessible resources for omics data analysis and interpretation for the genus Aspergillus. Furthermore, we have given a general example of how a well annotated genome can help improving GO annotation of related species to subsequently facilitate the interpretation of omics data. PMID- 21974741 TI - Identification of the abscisic acid receptor VvPYL1 in Vitis vinifera. AB - The phytohormone abscisic acid (ABA) plays a central role in many developmental processes and in responses to several abiotic stresses. Identification of the ABA receptor is a first step towards understanding ABA signalling. In this study, using homology analysis, we cloned three genes, named VvPYL1, VvPYL2 and VvPYL3, from Vitis vinifera. An isothermal titration calorimetry assay suggested that VvPYL1 could bind to ABA. A phosphatase activity assay demonstrated that VvPYL1 inhibits phosphatase activity of ABI1, a negative regulator of ABA signalling, in the presence of ABA. Subcellular localisation demonstrates that VvPYL1 is distributed in both the nucleus and cytosol, which is similar to the subcellular localisation of ABA receptors in Arabidopsis. We therefore conclude that VvPYL1 is an ABA receptor that modulates ABA signalling by inhibiting type 2C protein phosphatases (PP2Cs). PMID- 21974743 TI - Quantitative structure-activity relationships and docking studies of calcitonin gene-related peptide antagonists. AB - Defining the role of calcitonin gene-related peptide in migraine pathogenesis could lead to the application of calcitonin gene-related peptide antagonists as novel migraine therapeutics. In this work, quantitative structure-activity relationship modeling of biological activities of a large range of calcitonin gene-related peptide antagonists was performed using a panel of physicochemical descriptors. The computational studies evaluated different variable selection techniques and demonstrated shuffling stepwise multiple linear regression to be superior over genetic algorithm-multiple linear regression. The linear quantitative structure-activity relationship model revealed better statistical parameters of cross-validation in comparison with the non-linear support vector regression technique. Implementing only five peptide descriptors into this linear quantitative structure-activity relationship model resulted in an extremely robust and highly predictive model with calibration, leave-one-out and leave-20 out validation R(2) of 0.9194, 0.9103, and 0.9214, respectively. We performed docking of the most potent calcitonin gene-related peptide antagonists with the calcitonin gene-related peptide receptor and demonstrated that peptide antagonists act by blocking access to the peptide-binding cleft. We also demonstrated the direct contact of residues 28-37 of the calcitonin gene-related peptide antagonists with the receptor. These results are in agreement with the conclusions drawn from the quantitative structure-activity relationship model, indicating that both electrostatic and steric factors should be taken into account when designing novel calcitonin gene-related peptide antagonists. PMID- 21974742 TI - No evidence for depletion of carbohydrate pools in Scots pine (Pinus sylvestris L.) under drought stress. AB - The physiological mechanisms leading to Scots pine (Pinus sylvestris L.) decline in the dry inner alpine valleys are still unknown. Testing the carbon starvation hypothesis, we analysed the seasonal course of mobile carbohydrate pools (NSC) of Scots pine growing at a xeric and a dry-mesic site within an inner alpine dry valley (750 m a.s.l., Tyrol, Austria) during 2009, which was characterised by exceptional soil dryness. Although, soil moisture content dropped to ca. 10% at both sites during the growing season, NSC concentrations rose in all tissues (branch, stem, root) until the end of July, except in needles, where maxima were reached around bud break. NSC concentrations were not significantly different in the analysed tissues at the xeric and the dry-mesic site. At the dry-mesic site, NSC concentrations in the aboveground tree biomass were significantly higher during the period of radial growth. An accumulation of NSC in roots at the end of July indicates a change in carbon allocation after an early cessation in aboveground growth, possibly due to elevated belowground carbon demand. In conclusion, our results revealed that extensive soil dryness during the growing season did not lead to carbon depletion. However, even though carbon reserves were not exhausted, sequestration of carbohydrate pools during drought periods might lead to deficits in carbon supply that weaken tree vigour and drive tree mortality. PMID- 21974744 TI - Insulin resistance and pathological brain ageing. AB - Sir Harold Himsworth's prescient observations 75 years ago have recently been expanded to include a clear relationship between insulin resistance and central nervous system function. Insulin is a master regulator of corporeal ageing in all known species, determining the rate and expression of ageing in multiple body systems. Thus, it is not surprising that insulin also plays an important role in brain ageing and cognitive decline that is associated with pathological brain ageing. Brain ageing is accompanied by reduced insulin effectiveness, either by an inadequate cellular response to insulin or by insulin deficiency attributable to reduced insulin transport across the blood-brain barrier. Age-associated brain insulin abnormalities may contribute to cognitive decline in ageing, as have been documented in older adults with Type 2 diabetes mellitus and hypertension. With more extreme pathology, brain insulin resistance may be associated with neurogenerative diseases such as Alzheimer's disease, and the condition which precedes Alzheimer's disease, known as amnestic mild cognitive impairment. In the following review, we discuss the mechanisms through which insulin resistance may induce or potentiate pathological brain ageing and thereby create a neurobiological environment that promotes neurodegeneration and associated cognitive decline. This topic is timely, given that insulin resistance-associated conditions such as diabetes and obesity have reached epidemic proportions. The prevalence of such chronic conditions, in combination with a rapidly ageing population, may result in a corresponding increase in the prevalence of Alzheimer's disease and other cognitive disorders. Fortunately, insulin resistance-associated conditions are amenable to both pharmacologic and lifestyle interventions that may reduce the deleterious impact of insulin resistance on the ageing brain. PMID- 21974745 TI - A method for fabricating an implant-retained orbital prosthesis using the existing prosthesis. AB - This article describes a time-saving technique for fabricating a new implant retained orbital prosthesis using the patient's existing prosthesis. The location of the ocular component is transferred; the position and openings of the palpebral anatomic structures and the precise anatomic details of the existing orbital prosthesis are duplicated. Making the impression, fabricating the definitive cast, alignment of the ocular component, and completing the wax sculpture of the prosthesis are accomplished in one appointment. PMID- 21974746 TI - Working Inside for Smoking Elimination (Project W.I.S.E.) study design and rationale to prevent return to smoking after release from a smoke free prison. AB - BACKGROUND: Incarcerated individuals suffer disproportionately from the health effects of tobacco smoking due to the high smoking prevalence in this population. In addition there is an over-representation of ethnic and racial minorities, impoverished individuals, and those with mental health and drug addictions in prisons. Increasingly, prisons across the U.S. are becoming smoke free. However, relapse to smoking is common upon release from prison, approaching 90% within a few weeks. No evidence based treatments currently exist to assist individuals to remain abstinent after a period of prolonged, forced abstinence. METHODS/DESIGN: This paper describes the design and rationale of a randomized clinical trial to enhance smoking abstinence rates among individuals following release from a tobacco free prison. The intervention is six weekly sessions of motivational interviewing and cognitive behavioral therapy initiated approximately six weeks prior to release from prison. The control group views six time matched videos weekly starting about six weeks prior to release. Assessments take place in person 3 weeks after release and then for non-smokers every 3 months up to 12 months. Smoking status is confirmed by urine cotinine. DISCUSSION: Effective interventions are greatly needed to assist these individuals to remain smoke free and reduce health disparities among this socially and economically challenged group. TRIAL REGISTRATION: NCT01122589. PMID- 21974747 TI - Concerted or stepwise hydrogen transfer in the transfer hydrogenation of acetophenone catalyzed by ruthenium-acetamido complex: a theoretical mechanistic investigation. AB - In this paper, the mechanism of transfer hydrogenation of acetophenone catalyzed by ruthenium-acetamido complex was studied using density function theory (DFT) method. The catalytic cycle of transfer hydrogenation consists of hydrogen transfer (HT) step and dehydrogenation (DH) step of isopropanol (IPA). Inner sphere mechanism (paths 1 and 7) and outer sphere mechanism (paths 2-6) in HT step are fully investigated. Calculated results indicate that DH step of IPA (from (i)1 to (i)2) is the rate-determining step in the whole catalytic cycle, which has a potential energy barrier of 16.2 kcal/mol. On the other hand, the maximum potential energy barriers of paths 1-7 in the HT step are 5.9, 12.7, 24.4, 16.8, 23.7, 7.2, and 6.1 kcal/mol, respectively. The inner sphere pathways (paths 1 and 7) are favorable hydrogen transfer modes compared with outer sphere pathways, and the proton transferred to the oxygen atom of acetophenone comes from the hydroxyl group but not from amino group of acetamido ligand. Those theoretical results are in agreement with experimental report. However, in view of this DFT study in the inner sphere mechanism of HT step, hydride transfer and proton transfer are concerted and asynchronous hydrogen transfer but not a stepwise one, and hydride transfer precedes proton transfer in this case. PMID- 21974748 TI - Effect of water on solvation structure and dynamics of ions in the peptide bond environment: importance of hydrogen bonding and dynamics of the solvents. AB - The solvation structure and dynamics of ions in aqueous N-methylacetamide (NMA) solutions are calculated using classical molecular dynamics simulations. Our results are analyzed in terms of varying composition ranging from pure NMA to pure water. We also examined the effect of varying water content on the structure and dynamics of a neutral solute. Altogether we have simulated 38 different systems in the present work. It is found that water molecules have preference over NMA for the ions irrespective of their charge and size, whereas the neutral solute is preferably solvated by methyl groups of NMA. The calculated self diffusion coefficient values show comparatively slower dynamics for ions than the neutral solute which can be attributed to the stronger solvation of ions in aqueous NMA mixtures. Various dynamical properties associated with translational and rotational motion of solvents are also calculated, and similar slower dynamics of solvents is observed which can be attributed to the enhanced stability of the hydrogen bonds and formation of interspecies complexes in the mixtures. PMID- 21974749 TI - Nanomedicine(s) under the microscope. AB - Depending on the context, nanotechnologies developed as nanomedicines (nanosized therapeutics and imaging agents) are presented as either a remarkable technological revolution already capable of delivering new diagnostics, treatments for unmanageable diseases, and opportunities for tissue repair or highly dangerous nanoparticles, nanorobots, or nanoelectronic devices that will wreak havoc in the body. The truth lies firmly between these two extremes. Rational design of "nanomedicines" began almost half a century ago, and >40 products have completed the complex journey from lab to routine clinical use. Here we critically review both nanomedicines in clinical use and emerging nanosized drugs, drug delivery systems, imaging agents, and theranostics with unique properties that promise much for the future. Key factors relevant to the design of practical nanomedicines and the regulatory mechanisms designed to ensure safe and timely realization of healthcare benefits are discussed. PMID- 21974750 TI - Topical calcineurin inhibitors in the treatment of atopic dermatitis - an update on safety issues. AB - Atopic dermatitis is a common chronic skin disorder whose management is complex. Topical corticosteroids have been the mainstay of atopic dermatitis treatment for more than 50 years but have multiple side effects. Topical calcineurin inhibitors including tacrolimus and pimecrolimus are safe and efficacious in atopic dermatitis. In 2005 the FDA issued "black box" warnings for pimecrolimus cream and tacrolimus ointment because of potential safety risks, including skin cancers and lymphomas. However, these concerns are not supported by current data. Topical calcineurin inhibitors are particularly indicated for treating patients with atopic dermatitis in whom topical corticosteroid therapy cannot be employed or may cause irreversible side effects. They can be used advantageously in problem zones. A novel regimen of proactive treatment has been shown to prevent, delay and reduce exacerbations of atopic dermatitis. Therapy with topical calcineurin inhibitors should be managed by an experienced specialist and each patient should receive proper education on how to use them and what possible unwanted effects may be expected. PMID- 21974751 TI - Analysis of patch test referrals: influence of appropriateness of referrals on sensitization rate. AB - BACKGROUND: Few studies have addressed the frequency and the consequences of the appropriateness of referrals for patch testing. OBJECTIVES: To analyse the appropriateness of referrals for patch testing among patients seen in the Allergy Unit, University of Ferrara, and to evaluate whether this selection influences the results of the test. PATIENTS AND METHODS: One thousand six hundred and twenty-seven consecutive patients were enrolled, and 1528 patients were patch tested. On the basis of the history and clinical picture, the appropriateness of referrals for patch testing was judged. RESULTS: Of the patients, 82.30% attended the Allergy Unit with a clinical presentation and/or history considered to be an appropriate indication for patch testing. The rate of appropriate referrals for patch testing from dermatologists was significantly higher (p < 0.001) than that for referrals from other physicians. The sensitization rate was significantly higher among the appropriate referrals than among the inappropriate ones, both in the entire sample (p < 0.001) and in atopic patients (p = 0.012). CONCLUSIONS: Clinical experience was seen to be crucial for the appropriate selection of patients. Furthermore, appropriate referral for patch testing was shown to influence the sensitization rate. PMID- 21974752 TI - Effects of periadolescent fluoxetine and paroxetine on elevated plus-maze, acoustic startle, and swimming immobility in rats while on and off-drug. AB - RATIONALE: Whether selective serotonin reuptake inhibitors (SSRIs) exposure during adolescent brain development causes lasting effects remains unresolved. OBJECTIVE: Assess the effects of fluoxetine and paroxetine 60 days after adolescent exposure compared with when on-drug. METHODS: Male Sprague-Dawley littermates (41 litters) were gavaged on postnatal days 33-53 with fluoxetine (3 or 10 mg/kg/day), paroxetine (3, 10 or, 17 mg/kg/day), or water; half were tested while on-drug (21 litters) and half after 60 days off-drug (20 litters). RESULTS: The highest dose of the drugs reduced body weight gain during treatment that rebounded 1 week post-treatment. On-drug, no significant group differences were found on elevated plus maze time-in-open, zone entries, or latency to first open entry; however, the high dose of paroxetine significantly reduced head-dips (N=20/group). No significant effects were found on-drug for acoustic startle response/prepulse inhibition (ASR/PPI) although a trend (p<0.10) was seen, which after combining dose levels, showed a significant increase in ASR amplitude for both fluoxetine and paroxetine (N=20-21/group). No differences on immobility time were seen in the Porsolt forced swim test or in plasma corticosterone at the end of forced swim (N-19-21/group). Off-drug, no effects were seen in the elevated plus maze (N=16/group), ASR/PPI (N=20/group), forced swim (N=19-20/group), or plasma corticosterone (N=19/group). At the doses tested, fluoxetine and paroxetine induced minor effects with drug on-board but no residual, long-term adverse effects in rats 60 days after drug discontinuation. CONCLUSIONS: The data provide no evidence that fluoxetine or paroxetine have long-term adverse effects on the behaviors measured here after adolescent to young adult exposure. PMID- 21974753 TI - Usefulness of pulmonary function tests and blood gases in acute neuromuscular respiratory failure. AB - BACKGROUND AND PURPOSE: Define the usefulness of pulmonary function tests (PFT) and arterial blood gases (ABG) in patients admitted to the ICU with acute neuromuscular respiratory failure (NMRF). METHODS: We reviewed 76 patients admitted to an ICU at Mayo Clinic (Rochester) between 2003 and 2009 with acute NMRF defined as need for mechanical ventilation (MV) because of primary impairment of the peripheral nervous system. Poor functional outcome was defined as a modified Rankin score >3. RESULTS: Median age was 65years. The most frequent diagnosis was myasthenia gravis (25 patients); 54% of patients had no known neuromuscular diagnosis before admission, and 11% had no specific diagnosis at discharge. Median MV time was 16days; 14% of patients died during hospitalization, and 63% were severely disabled at discharge. Maximal expiratory pressure <=30cm H(2) O and maximal inspiratory pressure (MIP) worse than -28cm H2 O before MV were associated with need for invasive MV for longer than 7days (P=0.02). Indicators of chronic respiratory acidosis (low pH, high pCO2 , and high HCO3 ) before MV were associated with in-hospital death and poor functional outcome, but mostly in patients with progressive, untreatable neuromuscular diagnoses. CONCLUSIONS: In patients with primary acute NMRF, bedside PFT and ABG before MV can be used to predict evolution and outcome. Lower MIP and MEP portend prolonged MV and are more useful than forced vital capacity. Presentation with chronic respiratory acidosis is associated with high risk of in-hospital mortality and severe disability, especially in patients without treatable diagnoses. PMID- 21974754 TI - Implications of ambulatory blood pressure monitoring substudies on the interpretation of clinical trials in hypertension: should the threshold for drug therapy be lower in older patients? PMID- 21974755 TI - Keeping your arteries young: vascular health. PMID- 21974756 TI - It is time to fix the peer-review system. PMID- 21974757 TI - Influence of low high-density lipoprotein cholesterol on arterial stiffening and left ventricular diastolic dysfunction in essential hypertension. AB - The authors investigated whether high-density lipoprotein (HDL) cholesterol plays a role in arterial stiffening and left diastolic dysfunction in essential hypertension. Carotid arterial stiffness parameter and left ventricular (LV) diastolic function index were evaluated in 217 patients with essential hypertension. The correlations of dyslipidemia, especially low HDL cholesterol, to LV diastolic function and arterial stiffness were investigated in these patients. Arterial stiffness parameter increased with the increasing of E/Em (LV diastolic function index: the ratio of transmitral peak velocity of early filling to peak early diastolic motion velocity of mitral annulus) (r = 0.26, P<.01). In univariate regression analysis, HDL cholesterol was inversely associated with arterial stiffness parameter and E/Em (r = -0.23 and r = -0.27, respectively, P<.01). The association of HDL cholesterol with arterial stiffness and LV diastolic function was observed in both men and women. Triglycerides were weakly correlated with arterial stiffness parameter and E/Em, while low-density lipoprotein and total cholesterol were not. In multiple regression analysis, only low HDL cholesterol was found as an independent predictor for both arterial stiffness and LV diastolic dysfunction. Enhanced arterial stiffness is associated with LV diastolic dysfunction. Low HDL cholesterol may lead to the deterioration of both arterial stiffness and LV diastolic function in patients with essential hypertension. PMID- 21974758 TI - Serum calcium levels and hypertension among U.S. adults. AB - Serum calcium levels have been shown to be associated with cardiovascular disease (CVD); however, it is not clear whether serum calcium levels are related to hypertension, a risk factor for CVD. The authors examined the association between serum calcium and hypertension in a representative sample of US adults. A cross sectional study of 12,405 third National Health and Nutrition Examination Survey participants 20 years and older was conducted. Serum total and ionized calcium levels were analyzed as quartiles. The main outcome of interest was hypertension (n=3437), defined as self-reported use of antihypertensive medication and/or systolic blood pressure >=140 mm Hg or diastolic blood pressure >=90 mm Hg. Elevated serum total calcium levels were positively associated with hypertension, independent of potential confounders including C-reactive protein, estimated glomerular filtration rate, serum albumin, 25(OH)D, and phosphorous. Compared with the lowest quartile of serum total calcium (referent category), the multivariable odds ratio (95% confidence interval) of hypertension was 1.49 (1.15 1.93) for the highest quartile (P=.005). This association persisted in subgroup analyses stratified by sex, age, and race-ethnicity. In contrast, serum ionized calcium levels were not associated with hypertension. Higher serum total calcium levels are positively associated with hypertension in a representative sample of U.S. adults. PMID- 21974759 TI - Treating systolic hypertension in the very elderly with valsartan hydrochlorothiazide vs. either monotherapy: ValVET primary results. AB - This 16-week trial investigated the efficacy and safety of single-pill valsartan/hydrochlorothiazide (HCTZ) vs. the individual components in patients 70 years and older with systolic hypertension. Patients were randomized to valsartan/HCTZ 160/12.5 mg (n=128), HCTZ 12.5 mg (n=128), or valsartan 160 mg (n=128) for 4 weeks. Patients whose blood pressure (BP) was >=140/90 mm Hg at weeks 4, 8, or 12 were up-titrated to a maximum of valsartan/HCTZ 320/25 mg. Week 4 systolic BP reduction (primary efficacy outcome) was greater with valsartan/HCTZ than valsartan (-17.3 mm Hg vs. -8.6 mm Hg, P <.0001) but only marginally greater than HCTZ (-13.6 mm Hg, P =.096). Median time to BP control was shorter with valsartan/HCTZ (4 weeks) vs HCTZ (8 weeks, P<.05) or valsartan (12 weeks, P<.0001). Thiazide monotherapy was more effective than angiotensin receptor blocker monotherapy (by about 5 mm Hg), but greater antihypertensive efficacy was achieved by initiating treatment with combination valsartan/HCTZ in the elderly. PMID- 21974760 TI - Office and ambulatory blood pressure-lowering effects of combination valsartan/hydrochlorothiazide vs. hydrochlorothiazide-based therapy in obese, hypertensive patients. AB - The authors evaluated the blood pressure (BP)-lowering effects of combination valsartan/hydrochlorothiazide (HCTZ) vs. amlodipine/HCTZ in a 16-week, double blind, randomized, forced-titration study and ambulatory BP monitoring (ABPM) substudy involving centrally obese hypertensive patients 40 years and older. Patients were started on valsartan/HCTZ 160/12.5 mg or HCTZ 12.5 mg monotherapy, force-titrated at week 4 to valsartan/HCTZ 320/25 mg and HCTZ 25 mg, respectively. The HCTZ group initiated amlodipine 5 mg at week 8 and 10 mg at week 12. A subset of patients had 24-hour ABPM at baseline and weeks 8 and 16. At week 16 in the intent-to-treat population (n=401), valsartan/HCTZ and amlodipine/HCTZ lowered office systolic BP (-30.6 vs. -28.3 mm Hg; P=.14). In the ABPM subgroup (n=111), valsartan/HCTZ was more effective than amlodipine/HCTZ in reducing 24-hour systolic BP (-20.6 vs. -14.5 mm Hg; P=.011). In obese hypertensive patients, valsartan/HCTZ reduced office BP similar to amlodipine/HCTZ but lowered 24-hour systolic BP more. PMID- 21974761 TI - Associations between sleep disorders, sleep duration, quality of sleep, and hypertension: results from the National Health and Nutrition Examination Survey, 2005 to 2008. AB - Sleep is a contributing factor to optimal health and vitality. However, to date, no national study has evaluated the simultaneous relationship between sleep disorders, quality, and duration with hypertension. Using data from National Health and Nutrition Examination Survey (NHANES) (2005 to 2008), hypertension was defined by current use of antihypertensive medication or systolic blood pressure >=140 mm Hg or diastolic blood pressure >=90 mm Hg. Self-reported sleep disorders and duration were categorized from a single household interview question, and sleep quality was determined from several questions on sleeping habits. The prevalence of hypertension was 30.2% and 7.5%, and 33.0% and 52.1% reported having sleep disorders, short sleep, and poor sleep, respectively. After adjustment for demographic characteristics and comorbidities, having sleep disorders only was not significantly associated with hypertension (odds ratio [OR], 1.65; 95% confidence interval [CI], 0.73-3.77). However, this association was modified by sleep duration: significant associations were observed among adults with concurrent sleep disorders and short sleep (OR, 2.30; 95% CI, 1.49 3.56) and with sleep disorders, short sleep, and poor sleep (OR, 1.84; 95% CI, 1.13-2.98). These findings indicate an association between a combination of sleep problems and hypertension, but prospective studies are needed to understand the complex interplay between them. PMID- 21974762 TI - Hemodynamic and arrhythmogenic effects of cocaine in hypertensive individuals. AB - Despite the increased risk of myocardial infarction, aortic dissection, and arrhythmias in patients with hypertension who use cocaine, the hemodynamic and arrhythmogenic effects of cocaine use have not been well characterized in this population. The authors hypothesized that patients with hypertension demonstrate extreme, transient changes in arterial pressures as well as new arrhythmic activity during cocaine use. Ambulatory blood pressures, heart rates, and electrocardiograms (AECGs) were recorded for 48 hours in 10 patients with a history of hypertension who smoke cocaine. Active cocaine use was identified through patient diaries and manual activation of the blood pressure cuff. Of the 10 patients studied (6 men, 7 African Americans, age 49+/-8 years), 8 were taking antihypertensive medications. The mean blood pressure prior to cocaine use was 126/77 mm Hg and average increase in systolic, diastolic, and mean arterial pressure after use was 74 mm Hg, 30 mm Hg, and 45 mm Hg, respectively (P<.0001 for all). There was no significant change in heart rate. AECGs demonstrated arrhythmic activity during cocaine use, including 6 patients with increased atrial and ventricular ectopy, 2 patients with episodes of nonsustained atrial tachycardia, and 1 patient with 3 episodes of nonsustained monomorphic ventricular tachycardia. Cocaine use resulted in extreme elevations in arterial pressures in patients with hypertension taking medication. Cocaine use was also associated with an increase in arrhythmic activity. These findings may underlie the heightened risk of myocardial infarction, aortic dissection, and potentially lethal arrhythmias in patients with hypertension who use cocaine. PMID- 21974763 TI - Development and evaluation of a hypertension knowledge test for Korean hypertensive patients. AB - Patients' knowledge concerning high blood pressure (HBP) is a useful outcome measure in HBP education programs. However, valid and easy-to-use HBP knowledge assessment tools are scarce. The purpose of the study was to validate the HBP Knowledge Test (HKT) in two independent samples of Korean Americans with HBP (N=885). A total of 61% of the sample were women with a mean age of about 61 years (standard deviation=11.0) and 44% reported some college education or greater. Psychometric and item response theory analyses identified 21 items that fit a unidimensional model to form the HKT. Internal consistency was acceptable, with Cronbach's alpha=0.70. Construct validity testing revealed that patients with controlled BP had significantly higher HKT scores than those with uncontrolled BP (P=.012). The HKT is a simple questionnaire for assessing and monitoring HBP knowledge. It is sensitive to differences in blood pressure control status and should provide a valid, reliable, and standardized measure of HBP knowledge with wide relevance. PMID- 21974764 TI - The efficacy and safety of valsartan in obese and non-obese pediatric hypertensive patients. AB - This post hoc analysis assessed the efficacy and tolerability of valsartan for the treatment of hypertension in obese vs non-obese children and adolescents. After a 1-week antihypertensive washout period, 142 obese and 119 non-obese hypertensive children and adolescents aged 6 to 16 years were randomized to 2 weeks of once-daily treatment with valsartan 10 to 20 mg, 40 to 80 mg, or 80 to 160 mg, followed by re-randomization to either valsartan or placebo for an additional 2 weeks. Patients could continue to receive valsartan during an optional 52-week, open-label extension. Valsartan resulted in statistically significant (P<.05) and clinically relevant reductions in mean sitting blood pressure (BP), ranging from approximately 7/4 mm Hg (valsartan 10-20 mg) to 13/9 mm Hg (valsartan 80-160 mg) in both obese and non-obese patients. BP control was achieved in 44% of obese and 56% of non-obese patients. Following re randomization, non-obese patients experienced an increase in BP during placebo treatment, albeit levels remained below baseline, whereas BP reductions were maintained in valsartan recipients (P<.05). The most frequent adverse events during the open-label phase were headache and fever. Valsartan provides similar antihypertensive efficacy in obese and non-obese hypertensive children and adolescents, with good tolerability in both patient populations. PMID- 21974765 TI - Socioeconomic factors influencing the failure to measure the blood pressure of children during clinical examinations. AB - The authors measured the percentage of children aged 6 through 17 whose blood pressure (BP) was not measured during recent nonemergency clinical examination and assessed the relative importance of health, ability-to-pay, language, and race-ethnic factors in determining whether BP was measured. Using a pooled dataset from the Medical Expenditure Panel Survey (MEPS) for 2006 and 2007, the authors calculated the percentage of children whose BP was not measured using a sample of children aged 6 through 17 and constructed a logistic regression model to estimate the relative importance of health, economic, and social factors in the examiner's decision to measure BP. A total of 28.9% of children did not have their BP measured. Within this unmeasured group, 31% had a family history of hypertension, 9% had a family history of diabetes, and 5% had a body mass index >=32 kg/m2 . The logistic regression model of examiners' decisions indicates that social and economic factors strongly compete with health factors in determining which children not to measure. While examiners place many children at risk for hypertension in the measured pool, they also place many at-risk children in the unmeasured pool for economic and social reasons. PMID- 21974766 TI - Prevalence of hypertension in 9- to 10-year-old Icelandic school children. AB - The purpose of the study was to investigate blood pressure (BP) distribution, prevalence of hypertension, and correlation between BP and body mass index (BMI) in 9- to 10-year-old Icelandic children. Two manual and two automated BP measurements were performed in 1071 Icelandic children. Children with elevated BP underwent a second BP screening, and a third screening was performed if the BP was elevated at the second visit. Hypertension was defined as BP >=95th percentile at all three visits. White-coat hypertension was diagnosed in hypertensive children with normal 24-hour ambulatory BP. Of 970 children with complete data, 489 were girls (50.4%). The mean BP was 111/63 mm Hg in girls and 112/64 mm Hg in boys (P<.001). The prevalence of elevated BP was 13.1%, 6.0%, and 3.1% after the first, second, and third screen, respectively. The prevalence of sustained hypertension was 2.5% and an additional 0.6% had white-coat hypertension. A significant correlation between BMI and BP was observed (r=0.338, P<.001) and 8.6% of the obese children had hypertension. The prevalence of hypertension in 9- to 10-year-old Icelandic children is lower than indicated in recent reports and is associated with obesity. PMID- 21974767 TI - New prediction rule for incident hypertension: Atherosclerosis Risk in Communities (ARIC) Study/Cardiovascular Health Study (CHS). PMID- 21974768 TI - Revisiting evidence of blood pressure-dependent and independent effects of amlodipine on the risk of stroke. PMID- 21974769 TI - Spironolactone revisited. PMID- 21974770 TI - Treatment of Davener's dermatosis using a 1064-nm Q-switched Nd:YAG laser with low fluence. PMID- 21974771 TI - Multivariate analyses of salt stress and metabolite sensing in auto- and heterotroph Chenopodium cell suspensions. AB - Global warming increases plant salt stress via evaporation after irrigation, but how plant cells sense salt stress remains unknown. Here, we searched for correlation-based targets of salt stress sensing in Chenopodium rubrum cell suspension cultures. We proposed a linkage between the sensing of salt stress and the sensing of distinct metabolites. Consequently, we analysed various extracellular pH signals in autotroph and heterotroph cell suspensions. Our search included signals after 52 treatments: salt and osmotic stress, ion channel inhibitors (amiloride, quinidine), salt-sensing modulators (proline), amino acids, carboxylic acids and regulators (salicylic acid, 2,4-dichlorphenoxyacetic acid). Multivariate analyses revealed hirarchical clusters of signals and five principal components of extracellular proton flux. The principal component correlated with salt stress was an antagonism of gamma-aminobutyric and salicylic acid, confirming involvement of acid-sensing ion channels (ASICs) in salt stress sensing. Proline, short non-substituted mono-carboxylic acids (C2-C6), lactic acid and amiloride characterised the four uncorrelated principal components of proton flux. The proline-associated principal component included an antagonism of 2,4-dichlorphenoxyacetic acid and a set of amino acids (hydrophobic, polar, acidic, basic). The five principal components captured 100% of variance of extracellular proton flux. Thus, a bias-free, functional high-throughput screening was established to extract new clusters of response elements and potential signalling pathways, and to serve as a core for quantitative meta analysis in plant biology. The eigenvectors reorient research, associating proline with development instead of salt stress, and the proof of existence of multiple components of proton flux can help to resolve controversy about the acid growth theory. PMID- 21974772 TI - Editorial: context and conduct, and accessibility in scientific reporting. PMID- 21974773 TI - Hand warmer related corrosive injury. AB - INTRODUCTION: Corrosive injury of the esophagus and stomach is never been reported after intoxication of hand warmers. Herein we reported a case that had grade IIA corrosive injury found by endoscopic examination. CASE REPORT: An 84 year-old woman with a history of dementia ingested the contents of hand warmers. She had radiopaque patches in the stomach and duodenum. Upper endooscopic examination revealed corrosive injury of the esophagus and stomach. She recovered with the use of deferoxamine and proton pump inhibitor (PPI). DISCUSSION: The hand warmer contains activated charcoal, salt, and vermiculite, and 50% of iron powder. In previous literature, ingestions of one hand warmer packet or less are considered less toxic. But in our case, corrosive injury of the esophagus and stomach is obvious. CONCLUSION: It appears that significant toxicity will occur after ingestion of one hand warmer packet. Appropriate gastrointestinal decontamination and aggressive management are needed for all patients who are hand warmers intoxicated. PMID- 21974774 TI - Next-generation sequencing and syntenic integration of flow-sorted arms of wheat chromosome 4A exposes the chromosome structure and gene content. AB - Wheat is the third most important crop for human nutrition in the world. The availability of high-resolution genetic and physical maps and ultimately a complete genome sequence holds great promise for breeding improved varieties to cope with increasing food demand under the conditions of changing global climate. However, the large size of the bread wheat (Triticum aestivum) genome (approximately 17 Gb/1C) and the triplication of genic sequence resulting from its hexaploid status have impeded genome sequencing of this important crop species. Here we describe the use of mitotic chromosome flow sorting to separately purify and then shotgun-sequence a pair of telocentric chromosomes that together form chromosome 4A (856 Mb/1C) of wheat. The isolation of this much reduced template and the consequent avoidance of the problem of sequence duplication, in conjunction with synteny-based comparisons with other grass genomes, have facilitated construction of an ordered gene map of chromosome 4A, embracing >=85% of its total gene content, and have enabled precise localization of the various translocation and inversion breakpoints on chromosome 4A that differentiate it from its progenitor chromosome in the A genome diploid donor. The gene map of chromosome 4A, together with the emerging sequences of homoeologous wheat chromosome groups 4, 5 and 7, represent unique resources that will allow us to obtain new insights into the evolutionary dynamics between homoeologous chromosomes and syntenic chromosomal regions. PMID- 21974775 TI - Statistical learning is related to reading ability in children and adults. AB - There is little empirical evidence showing a direct link between a capacity for statistical learning (SL) and proficiency with natural language. Moreover, discussion of the role of SL in language acquisition has seldom focused on literacy development. Our study addressed these issues by investigating the relationship between SL and reading ability in typically developing children and healthy adults. We tested SL using visually presented stimuli within a triplet learning paradigm and examined reading ability by administering the Wide Range Achievement Test (WRAT-4; Wilkinson & Robertson, 2006). A total of 38 typically developing children (mean age of 9;5 years, range 6;4-12;5) and 37 healthy adults (mean age of 21 years, range 18-34) were assessed. In children, SL was significantly related to reading ability. Importantly, this relationship was independent of grade and also age. The adult data, too, revealed that SL was significantly related to reading ability. A regression analysis of the combined child and adult data revealed that SL accounted for a unique amount of variance in reading ability, after age and attention had been taken into consideration. For the first time, this study provides empirical evidence that a capacity for more effective SL is related to higher reading ability in the general population. PMID- 21974776 TI - Esthesioneuroblastoma chemotherapy and radiotherapy for extensive disease: a case report. AB - Malignant tumors of the nasal cavity are rare. We report the case of a 48 years old man who consulted us with a 2-year history of progressive nasal obstruction, occasional epistaxis, facial pain, and watering of the eyes. A diagnosis of olfactory neuroblastoma was established by histopathology and confirmed by immunohistochemistry. On staging, the mass was classified as a Kadish stage C tumor with extensive involvement of the nasal cavities, nasopharynx, paranasal sinuses and orbit. Endoscopic excision of the mass was done. Traditionally the mainstay of treatment in such locally advanced patients is craniofacial resection followed by adjuvant radiotherapy. Our patient was treated with limited surgery and chemoradiation. Patient is free of recurrence at a follow-up of 5 years. This case report demonstrates the potential efficacy of planned combined modality therapy, including limited surgery and early chemoradiation in the control of locally advanced olfactory neuroblastoma. PMID- 21974777 TI - Acetabular fractures following rugby tackles: a case series. AB - INTRODUCTION: Rugby is the third most popular team contact sport in the world and is increasing in popularity. In 1995, rugby in Europe turned professional, and with this has come an increased rate of injury. CASE PRESENTATION: In a six-month period from July to December, two open reduction and internal fixations of acetabular fractures were performed in young Caucasian men (16 and 24 years old) who sustained their injuries after rugby tackles. Both of these cases are described as well as the biomechanical factors contributing to the fracture and the recovery. Acetabular fractures of the hip during sport are rare occurrences. CONCLUSION: Our recent experience of two cases over a six-month period creates concern that these high-energy injuries may become more frequent as rugby continues to adopt advanced training regimens. Protective equipment is unlikely to reduce the forces imparted across the hip joint; however, limiting 'the tackle' to only two players may well reduce the likelihood of this life-altering injury. PMID- 21974778 TI - Cloning, expression and purification of extracellular serine protease Esp, a biofilm-degrading enzyme, from Staphylococcus epidermidis. AB - AIMS: Staphylococcus epidermidis Esp, an extracellular serine protease, inhibits Staphylococcus aureus biofilm formation and nasal colonization. To further expand the biotechnological applications of Esp, we developed a highly efficient and economic method for the purification of recombinant Esp based on a Brevibacillus choshinensis expression-secretion system. METHODS AND RESULTS: The esp gene was fused with the N-terminal Sec-dependent signal sequence of the B. choshinensis cell wall protein and a C-terminal hexa-histidine-tag gene. The recombinant Esp was expressed and secreted into the optimized medium as an immature form and subsequently activated by thermolysin. The mature Esp was easily purified by a single purification step using nickel affinity chromatography and showed proteolytic activity as well as Staph. aureus biofilm destruction activity. CONCLUSIONS: The purification yield of the developed extracellular production system was 5 mg recombinant mature Esp per 20-ml culture, which was much higher than that of an intracellular production system in Escherichia coli (3 mg recombinant Esp per 1-l culture). SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings will be a powerful tool for the production and purification of recombinant Esp and also applicable to a large variety of recombinant proteins used for basic researches and biotechnological applications. PMID- 21974779 TI - Interactive effects of salinity and phosphorus availability on growth, water relations, nutritional status and photosynthetic activity of barley (Hordeum vulgare L.). AB - The interactive effects of salinity and phosphorus availability on growth, water relations, nutritional status and photosynthetic activity were investigated in barley (Hordeum vulgare L. cv. Manel). Seedlings were grown hydroponically under low or sufficient phosphorus (P) supply (5 or 180 MUmol KH(2) PO(4) plant(-1) week(-1) , respectively), with or without 100 mm NaCl. Phosphorus deficiency or salinity significantly decreased whole plant growth, leaf water content, leaf osmotic potential and gas exchange parameters, with a more marked impact of P stress. The effect of both stresses was not additive since the response of plants to combined salinity and P deficiency was similar to that of plants grown under P deficiency alone. In addition, salt-treated plants exposed to P deficiency showed higher salt tolerance compared to plants grown with sufficient P supply. This was related to plant ability to significantly increase root:shoot DW ratio, root length, K(+)/Na(+) ratio, leaf proline and soluble sugar concentrations and total non-enzymatic antioxidant capacity, together with restricting Na(+) accumulation in the upper leaves. As a whole, our results indicate that under concomitant exposure to both salt and P deficiency, the impact of the latter constraint is pre-dominant. PMID- 21974780 TI - Parsimonious discovery of synergistic drug combinations. AB - Combination therapies that enhance efficacy or permit reduced dosages to be administered have seen great success in a variety of therapeutic applications. More fundamentally, the discovery of epistatic pathway interactions not only informs pharmacologic intervention but can be used to better understand the underlying biological system. There is, however, no systematic and efficient method to identify interacting activities as candidates for combination therapy and, in particular, to identify those with synergistic activities. We devised a pooled, self-deconvoluting screening paradigm for the efficient comprehensive interrogation of all pairs of compounds in 1000-compound libraries. We demonstrate the power of the method to recover established synergistic interactions between compounds. We then applied this approach to a cell-based screen for anti-inflammatory activities using an assay for lipopolysaccharide/interferon-induced acute phase response of a monocytic cell line. The described method, which is >20 times as efficient as a naive approach, was used to test all pairs of 1027 bioactive compounds for interleukin-6 suppression, yielding 11 pairs of compounds that show synergy. These 11 pairs all represent the same two activities: beta-adrenergic receptor agonists and phosphodiesterase-4 inhibitors. These activities both act through cyclic AMP elevation and are known to be anti-inflammatory alone and to synergize in combination. Thus we show proof of concept for a robust, efficient technique for the identification of synergistic combinations. Such a tool can enable qualitatively new scales of pharmacological research and chemical genetics. PMID- 21974781 TI - A mouse model of reverse cardiac remodelling following banding-debanding of the ascending aorta. AB - AIM: Myocardial remodelling during pressure overload might contribute to development of heart failure. Reverse remodelling normally occurs following aortic valve replacement for aortic stenosis; however, the details and regulatory mechanisms of reverse remodelling remain unknown. Thus, an experimental model of reverse remodelling would allow for studies of this process. Although models of aortic banding are widely used, only few reports of debanding models exist. The aim of this study was to establish a banding-debanding model in the mouse with repetitive careful haemodynamic evaluation by high-resolution echocardiography. METHODS: C57Bl/6 mice were subjected to ascending aortic banding and subsequent debanding. Cardiac geometry and function were evaluated by echocardiography, and left ventricular myocardium was analysed by histology and quantitative real-time polymerase chain reaction. RESULTS: The degree of aortic banding was controlled by non-invasive estimation of the gradient, and we found a close correlation between left ventricular mass estimated by echocardiography and weight at the time of killing. Aortic banding led to left ventricular hypertrophy, fibrosis and expression of foetal genes, indicating myocardial remodelling. Echocardiography revealed concentric left ventricular remodelling and myocardial dysfunction. Following debanding, performed via a different incision, there was rapid regression of left ventricular weight and normalization of both cardiac geometry and function by 14 days. CONCLUSIONS: We have established a reproducible and carefully characterized mouse model of reverse remodelling by banding and debanding of the ascending aorta. Such a model might contribute to increased understanding of the reversibility of cardiac pathology, which in turn might give rise to new strategies in heart failure treatment. PMID- 21974782 TI - Distinct modes of adventitious rooting in Arabidopsis thaliana. AB - The literature describes different rooting protocols for Arabidopsis thaliana as models to study adventitious rooting, and results are generally perceived as comparable. However, there is a lack of investigations focusing on the distinct features, advantages and limitations of each method in the study of adventitious rooting with both wild-type (WT) ecotypes and their respective mutants. This investigation was undertaken to evaluate the adventitious rooting process in three different experimental systems, all using A. thaliana, analysing the same rooting parameters after transient exposure to auxin (indole-3-acetic acid) and control conditions: excised leaves, de-rooted plants and etiolated seedlings. The founding tissues and sites of origin of roots differed depending on the system used, whereas all rooting patterns were of the direct type (i.e., without callus formation). None of the systems had an absolute requirement for exogenous auxin, although rooting was enhanced by this phytohormone, with the exception of de rooted plants, which had adventitious rooting strongly inhibited by exogenous auxin. Root elongation was much favoured in isolated leaves. Auxin-overproducing mutants could not be used in the detached leaf system due to precocious senescence; in the de-rooted plant system, these mutants had a WT-like rooting response, whereas the expression of the 'rooty' phenotype was only evident in the etiolated seedling system. Adventitious rooting of etiolated WT seedlings in the presence of exogenous auxin was inhibited by exogenous flavonoids, which act as auxin transport inhibitors; surprisingly, the flavonoid-deficient mutant chs had a lower rooting response compared to WT. Although Arabidopsis is an excellent model system to study adventitious rooting, physiological and developmental responses differed significantly, underlining the importance of avoiding data generalisation on rooting responses derived from different experimental systems with this species. PMID- 21974783 TI - Expression of amnionless in mouse testes and Leydig cells. AB - Vitamin B(12) (cobalamin) deficiency results in atrophy of seminiferous tubules and aplasia of spermatozoa and spermatid. The transmembrane protein amnionless (AMN) directs endocytosis of cubilin with its ligand, contributing to intrinsic factor-vitamin B(12) absorption. To understand vitamin B(12) transport in testis, we analysed AMN expression in developing mouse testes and in Leydig cells and speculated the possible role of AMN in testis. In testes, Amn mRNA levels were low until 14 days post partum (pp) and markedly increased from puberty onwards. In the interstitium, Amn mRNA levels were low at 14 days pp and increased at puberty (28 days pp) together with 3-beta-hydroxysteroid dehydrogenase type 6 mRNA. Strong AMN immunoreactivity was observed in early spermatocytes from 7 days pp, suggesting that AMN participates in meiosis. In Leydig cells, AMN was not observed until 14 days pp but was strongly expressed after 28 days pp, suggesting a positive relationship between AMN expression and functional differentiation of adult Leydig cells. Together, AMN may participate in meiosis in early spermatocytes and in functional differentiation of adult Leydig cells through the mediation of vitamin B(12) transport in the mouse testes. This is the first report on AMN expression in the germ cells and soma of mammalian testes. PMID- 21974784 TI - Photophysics of the interaction between a fluorescein derivative and Ficoll. AB - Ficoll has been widely used as a crowding agent to mimic intracellular media because it is believed to be noninteracting and is composed of mixed sizes such that smaller and larger diffusing solutes can be studied. Due to the interest that the fluorescent dye 9-[1-(2-methyl-4-methoxyphenyl)]-6-hydroxy-3H-xanthen-3 one (TG-II) as a fluorometric probe of phosphate ions in intracellular media could generate, we describe the spectral characteristics of the system TG-II Ficoll in aqueous solution by means of absorption spectroscopy, steady-state fluorescence, time-resolved fluorescence, time-resolved emission spectroscopy, and fluorescence lifetime correlation spectroscopy. The spectral characteristics found are consistent with the formation of an adsorption complex on the surface of Ficoll, probably due to hydrogen bonding between TG-II and Ficoll. In addition, the diffusion coefficient calculated for the association was similar to the diffusion coefficient previously recovered for Ficoll in the same experimental conditions. Therefore, our overall data clearly demonstrate that Ficoll is not an inert crowding agent when in the presence of fluorescein derivative dyes. PMID- 21974785 TI - Translating long-term potentiation from animals to humans: a novel method for noninvasive assessment of cortical plasticity. AB - Long-term potentiation (LTP) is a synaptic mechanism underlying learning and memory that has been studied extensively in laboratory animals. The study of LTP recently has been extended into humans with repetitive sensory stimulation to induce cortical LTP. In this review article, we will discuss past results from our group demonstrating that repetitive sensory stimulation (visual or auditory) induces LTP within the sensory cortex (visual/auditory, respectively) and can be measured noninvasively with electroencephalography or functional magnetic resonance imaging. We will discuss a number of studies that indicate that this form of LTP shares several characteristics with the synaptic LTP described in animals: it is frequency dependent, long-lasting (> 1 hour), input-specific, depotentiates with low-frequency stimulation, and is blocked by N-methyl-D aspartate receptor blockers in rats. In this review, we also present new data with regard to the behavioral significance of human sensory LTP. These advances will permit enquiry into the functional significance of LTP that has been hindered by the absence of a human model. The ability to elicit LTP with a natural sensory stimulus noninvasively will provide a model system allowing the detailed examination of synaptic plasticity in normal subjects and might have future clinical applications in the diagnosis and assessment of neuropsychiatric and neurocognitive disorders. PMID- 21974786 TI - Mirror neuron activity associated with social impairments but not age in autism spectrum disorder. AB - BACKGROUND: The neurobiology of autism spectrum disorder (ASD) is not particularly well understood, and biomedical treatment approaches are therefore extremely limited. A prominent explanatory model suggests that social-relating symptoms may arise from dysfunction within the mirror neuron system, while a recent neuroimaging study suggests that these impairments in ASD might reduce with age. METHODS: Participants with autism spectrum disorder (i.e., DSM-IV autistic disorder or Asperger's disorder) (n = 34) and matched control subjects (n = 36) completed a transcranial magnetic stimulation study in which corticospinal excitability was assessed during the observation of hand gestures. RESULTS: Regression analyses revealed that the ASD group presented with significantly reduced corticospinal excitability during the observation of a transitive hand gesture (relative to observation of a static hand) (p < .05), which indicates reduced putative mirror neuron system activity within ventral premotor cortex/inferior frontal gyrus. Among the ASD group, there was also a negative association between putative mirror neuron activity and self-reported social-relating impairments, but there was no indication that mirror neuron impairments in ASD decrease with age. CONCLUSIONS: These data provide general support for the mirror neuron hypothesis of autism; researchers now must clarify the precise functional significance of mirror neurons to truly understand their role in the neuropathophysiology of ASD and to determine whether they should be used as targets for the treatment of ASD. PMID- 21974791 TI - Addressing the complexity conundrum in and of nursing. PMID- 21974787 TI - Hostility and cellular aging in men from the Whitehall II cohort. AB - BACKGROUND: Hostility is associated with a significantly increased risk of age related disease and mortality, yet the pathophysiological mechanisms involved remain unclear. Here we investigated the hypothesis that hostility might impact health by promoting cellular aging. METHODS: We tested the relationship between cynical hostility and two known markers of cellular aging, leukocyte telomere length (TL) and leukocyte telomerase activity (TA), in 434 men and women from the Whitehall II cohort. RESULTS: High-hostile men had significantly shorter leukocyte TL than their low-hostile counterparts. They also had elevated leukocyte TA, with a significantly increased likelihood of having both short TL and high TA, compared with low-hostile individuals. CONCLUSIONS: Because telomerase is known to counteract telomere shortening by synthesizing telomeric DNA repeats, particularly in the context of shortened telomeres, heightened TA might represent a compensatory response in high-hostile individuals. The relationship between hostility and disease is stronger in men than in women, and men generally have a shorter life expectancy than women. Our findings suggest that telomere attrition might represent a novel mechanism mediating the detrimental effects of hostility on men's health. PMID- 21974788 TI - Dimensional brain-behavior relationships in children with attention deficit/hyperactivity disorder. AB - BACKGROUND: Emerging neuroscientific and genetic findings emphasize the dimensional rather than the categorical aspects of psychiatric disorders. However, the integration of dimensional approaches within the current categorical diagnostic framework remains unclear. Here, we used resting state functional magnetic resonance imaging to examine whether dimensional measures of psychiatric symptomatology capture brain-behavior relationships unaccounted for by categorical diagnoses. Additionally, we examined whether dimensional brain behavior relationships are modified by the presence of a categorically defined illness, attention-deficit/hyperactivity disorder (ADHD). METHODS: Resting state functional magnetic resonance imaging scans were collected from 37 typically developing children (aged 10.2 +/- 2; 21 female subjects) and 37 children meeting DSM-IV Text Revision criteria for ADHD (9.7 +/- 2; 11 female subjects). Parent rated Child Behavior Checklist Externalizing and Internalizing scores served as dimensional measures in our analyses of default network (DN) resting state functional connectivity (RSFC). RESULTS: Regardless of diagnosis, we observed several significant relationships between DN RSFC and both internalizing and externalizing scores. Increased internalizing scores were associated with stronger positive intra-DN RSFC, while increased externalizing scores were associated with reduced negative RSFC between DN and task-positive regions such as dorsal anterior cingulate cortex. Several of these brain-behavior relationships differed depending on the categorical presence of ADHD. CONCLUSIONS: Our findings suggest that while categorical diagnostic boundaries provide an inadequate basis for understanding the pathophysiology of psychiatric disorders, psychiatric illness cannot be viewed simply as an extreme of typical neural or behavioral function. Efforts to understand the neural underpinnings of psychiatric illness should incorporate both categorical and dimensional clinical assessments. PMID- 21974792 TI - Evaluation of the Scrub Practitioners' List of Intraoperative Non-Technical Skills system. AB - BACKGROUND: The Scrub Practitioners' List of Intraoperative Non-Technical Skills (SPLINTS) system is a new tool for training and assessing scrub practitioner (nurse, technician) behaviours during surgical operations. OBJECTIVES: The aim of the study was to test the psychometric properties including inter-rater reliability of the prototype SPLINTS behavioural rating system. METHODS: Experienced scrub practitioners (n=34) attended a one-day session where they received background training in human factors and non-technical skills and were also trained to use the SPLINTS system. They then used SPLINTS to rate the scrub practitioners' non-technical skill performance in seven standardized simulated, surgical scenarios. RESULTS: Reliability, measured by within-group agreement (r(wg)) for the three skill categories and six out of nine elements, was acceptable (r(wg)>0.7). Participants were within one scale point of expert ratings in >90% of skill categories and elements, and could use SPLINTS to score performance with a reasonable level of accuracy. There was good internal consistency of the system: absolute mean difference was M<0.2 of a scale point for all three categories. Participants were surveyed and they indicated that the system was complete and usable as an assessment tool. CONCLUSION: The reliability of the SPLINTS system was deemed to be adequate for assessing scrub practitioners' non-technical skills in simulated, standardized, video scenarios. On the basis of these results, the system can now move on to usability testing in the real operating theatre. PMID- 21974793 TI - The presence of resilience is associated with a healthier psychological profile in intensive care unit (ICU) nurses: results of a national survey. AB - OBJECTIVE: ICU nurses are repeatedly exposed to work related stresses resulting in the development of psychological disorders including posttraumatic stress disorder and burnout syndrome. Resilience is a learnable multidimensional characteristic enabling one to thrive in the face of adversity. In a national survey, we sought to determine whether resilience was associated with healthier psychological profiles in intensive care unit nurses. DESIGN: Surveys were mailed to 3500 randomly selected ICU nurses across the United States and included: demographic questions, the Posttraumatic Diagnostic Scale, Hospital Anxiety and Depression Scale, Maslach Burnout Inventory and the Connor-Davidson Resilience Scale. MEASUREMENTS AND MAIN RESULTS: Overall, 1239 of the mailed surveys were returned for a response rate of 35%, and complete data was available on a total of 744 nurses. Twenty-two percent of the intensive care unit nurses were categorized as being highly resilient. The presence of high resilience in these nurses was significantly associated with a lower prevalence of posttraumatic stress disorder, symptoms of anxiety or depression, and burnout syndrome (<0.001 for all comparisons). In independent multivariable analyses adjusting for five potential confounding variables, the presence of resilience was independently associated with a lower prevalence of posttraumatic stress disorder (p<0.001), and a lower prevalence of burnout syndrome (p<0.001). CONCLUSIONS: The presence of psychological resilience was independently associated with a lower prevalence of posttraumatic stress disorder and burnout syndrome in intensive care unit nurses. Future research is needed to better understand coping mechanisms employed by highly resilient nurses and how they maintain a healthier psychological profile. PMID- 21974794 TI - Nasogastric feeding practices: a survey using clinical scenarios. AB - BACKGROUND: Bolus nasogastric tube feeding is common. Unsafe practices such as failure to confirm tube placement can result in death. It is vital to ensure that nurses are adopting safe practices. OBJECTIVE: To evaluate nurses' practices on bolus nasogastric feeding relating to verification of tube placement, management of gastric residual volume, and response to complications during feeding. DESIGN: Cross-sectional, self-administered survey using clinical scenarios. SETTING AND PARTICIPANTS: All nurses who worked in the general wards in a tertiary hospital in August 2008. METHODS: We developed six clinical scenarios to describe common clinical situations in nurses' daily practices. Participants were instructed to choose the responses that best reflected their practices, and to return the completed questionnaires to the study member present. RESULTS: The survey participation rate was 99.5% (1203 nurses). Seventy-six percent would choose two or more methods to verify placement when they were in doubt. Percentage of hydrogen (pH) testing was the most common first method of checking tube placement. The second and third self-reported methods were auscultation and the bubble test. Few chose radiography to confirm tube placement. When the aspirate was pH 7, and in the presence of positive auscultation, most participants would take further steps to confirm placement. There were variations in the nurses' responses on managing the gastric residual volume, with 78.1% indicating that they would return the aspirate. Most nurses lacked the knowledge to effectively manage patients' distress during tube feeding. CONCLUSIONS: The findings showed that the majority of participants reported that they would exercise due caution by taking additional measures to check tube placement when in doubt. The practice gaps identified in the study highlighted a need to realign our care to best practices. Following the study, we revised the institution's guideline, reinforced specific safety precautions on nasogastric feeding, and incorporated clinical scenarios in our training. PMID- 21974795 TI - Full-mouth rehabilitation of an edentulous patient with Papillon-Lefevre syndrome using dental implants: a clinical report. AB - Papillon-Lefevre syndrome (PLS) is a rare autosomal recessive disorder. The oral manifestations of the syndrome include rapidly progressive periodontal disease resulting in premature exfoliation of primary and permanent dentitions. Patients are often edentulous at an early age and require prosthodontic treatment. This report is the oral rehabilitation of an edentulous 21-year-old woman with PLS. Treatment included maxillary and mandibular fixed prostheses supported by osseointegrated dental implants. At the 4-year follow-up, the patient presented significant improvements in oral function and psychosocial activities and no prosthetic complications. PMID- 21974796 TI - Effect of magnesium sulphate on bleeding during lumbar discectomy. AB - We assessed the effect of magnesium on the amount of bleeding, coagulation profiles and surgical conditions during lumbar discectomy under general anaesthesia. Forty patients, of ASA physical status 1-2 and aged 18-65 years, undergoing single-level microscopic lumbar discectomy, were randomly assigned to magnesium sulphate (50 mg.kg(-1) in 100 ml saline over 10 min followed by a continuous infusion of 20 mg.kg.h(-1) ) or saline. The mean (SD) estimated blood loss was 190 (95) and 362 (170) ml in the magnesium and saline groups, respectively (mean difference = 172 ml; 95% CI 84-260 ml). The median (IQR [range]) Fromme's scale score for surgical conditions for the magnesium and saline groups were 2 (2-3 [2-3]) and 3 (2-3 [3-4]), respectively (p < 0.05). The bleeding time, haemoglobin, platelet count, prothrombin time, international normalised ratio and fibrinogen levels were similar in the two groups. The activated partial thromboplastin time was prolonged in the magnesium group immediately postoperatively and at 6 h after surgery. After the bolus of magnesium, the heart rate was higher and the mean arterial pressure lower in the magnesium group. The use of magnesium sulphate during lumbar discectomy decreases blood loss, and provides better surgical conditions without marked haemodynamic effects. PMID- 21974797 TI - Neuroendocrine tumor presenting like lymphoma: a case report. AB - INTRODUCTION: Neuroendocrine tumors are a rare but diverse group of malignancies that arise in a wide range of organ systems, including the mediastinum. Differential diagnosis includes other masses arising in the middle mediastinum such as lymphoma, pericardial, bronchogenic and enteric cysts, metastatic tumors, xanthogranuloma, systemic granuloma, diaphragmatic hernia, meningocele and paravertebral abscess. CASE PRESENTATION: We present a case of 42-year-old Caucasian man with a neuroendocrine tumor of the middle-posterior mediastinum and liver metastases, which resembled a lymphoma on magnetic resonance imaging. CONCLUSION: The differential diagnosis in patients with mediastinal masses and liver lesions should include neuroendocrine tumor. PMID- 21974798 TI - Alimentary fluoride intake in preschool children. AB - BACKGROUND: The knowledge of background alimentary fluoride intake in preschool children is of utmost importance for introducing optimal and safe caries preventive measures for both individuals and communities. The aim of this study was to assess the daily fluoride intake analyzing duplicate samples of food and beverages. An attempt was made to calculate the daily intake of fluoride from food and swallowed toothpaste. METHODS: Daily alimentary fluoride intake was measured in a group of 36 children with an average age of 4.75 years and an average weight of 20.69 kg at baseline, by means of a double plate method. This was repeated after six months. Parents recorded their child's diet over 24 hours and collected duplicated portions of food and beverages received by children during this period. Pooled samples of food and beverages were weighed and solid food samples were homogenized. Fluoride was quantitatively extracted from solid food samples by a microdiffusion method using hexadecyldisiloxane and perchloric acid. The content of fluoride extracted from solid food samples, as well as fluoride in beverages, was measured potentiometrically by means of a fluoride ion selective electrode. RESULTS: Average daily fluoride intake at baseline was 0.389 (SD 0.054) mg per day. Six months later it was 0.378 (SD 0.084) mg per day which represents 0.020 (SD 0.010) and 0.018 (SD 0.008) mg of fluoride respectively calculated per kg bw/day.When adding the values of unwanted fluoride intake from the toothpaste shown in the literature (0.17-1.21 mg per day) the estimate of the total daily intake of fluoride amounted to 0.554-1.594 mg/day and recalculated to the child's body weight to 0.027-0.077 mg/kg bw/day. CONCLUSIONS: In the children studied, observed daily fluoride intake reached the threshold for safe fluoride intake. When adding the potential fluoride intake from swallowed toothpaste, alimentary intake reached the optimum range for daily fluoride intake. These results showed that in preschool children, when trying to maximize the benefit of fluoride in caries prevention and to minimize its risk, caution should be exercised when giving advice on the fluoride containing components of child's diet or prescribing fluoride supplements. PMID- 21974799 TI - Sex specific changes in placental growth and MAPK following short term maternal dexamethasone exposure in the mouse. AB - OBJECTIVES: Maternal glucocorticoid (GC) exposure during pregnancy can alter fetal development and program the onset of disease in adult offspring. The placenta helps protect the fetus from excess GC exposure but is itself susceptible to maternal insults and may be involved in sex dependant regulation of fetal programming. This study aimed to investigate the effects of maternal GC exposure on the developing placenta. STUDY DESIGN AND MAIN OUTCOME MEASURES: Pregnant mice were treated with dexamethasone (DEX-1 MUg/kg/h) or saline (SAL) for 60 h via minipump beginning at E12.5. Placentas were collected at E14.5 and E17.5 and the expression of growth factors and placental transporters examined by real-time PCR and/or Western blot. Histological analysis was performed to assess for morphological changes. RESULTS: At E14.5, DEX exposed male and female fetuses had a lower weight compared to SAL animals but placental weight was lower in females only. Hsd11b2 and Vegfa gene expression was increased and MAPK1 protein expression decreased in the placentas of females only. At E17.5 placental and fetal body weights were similar and differences in MAPK were no longer present although HSD11B2 protein was elevated in placentas of DEX females. Levels of glucose or amino acid transporters were unaffected. CONCLUSIONS: Results suggest sex specific responses to maternal GCs within the placenta. Decreased levels of MAPK protein in placentas of female fetuses suggest alterations in the MAPK pathway may contribute to the lower placental weights in this sex. This may contribute towards sex specific fetal programming of adult disease. PMID- 21974800 TI - DNA repair gene polymorphisms and risk of early onset colorectal cancer in Lynch syndrome. AB - DNA repair plays a pivotal role in maintaining genomic integrity with over 130 genes involved in various repair pathways that include base excision repair, nucleotide excision repair, double strand break repair and DNA mismatch repair. Polymorphisms within genes that are involved in these processes have been widely reported to be associated with cancer susceptibility in an extensive range of malignancies that include colorectal cancer (CRC). Lynch syndrome is caused by inherited germline mutations in DNA mismatch repair genes, predominantly in MLH1 and MSH2, that predispose to a variety of epithelial malignancies, most notably CRC. Despite being a relatively well understood hereditary cancer syndrome there remain several questions in relation to genetic influences on disease expression. Since Lynch syndrome is associated with a breakdown in DNA mismatch repair variation in other DNA repair genes may influence disease expression. In this report we have genotyped 424 Australian and Polish Lynch syndrome participants for eight common DNA repair gene polymorphisms to assess any association with the age of CRC onset. The DNA repair gene SNPs included in the study were: BRCA2 (rs11571653), MSH3 (rs26279), Lig4 (rs1805386), OGG1 (rs1052133), XRCC1 (rs25487), XRCC2 (rs3218536 and rs1799793) and XRCC3 (rs861539). Cox multi variant regression modelling failed to provide any convincing evidence of an effect in any of the polymorphisms analysed. The data suggest that polymorphisms in DNA repair genes do not contribute to cancer risk in a population of CRC patients who are at increased risk of disease as a result in a deficiency of DNA mismatch repair. PMID- 21974801 TI - Concomitant pulmonary and thyroid tumors identified by FDG PET/CT and immunohistochemical techniques. AB - BACKGROUND: The exact diagnosis of double primary papillary adenocarcinoma of thyroid and lung is even rarer, to our knowledge no report in the literature by [18F]-2-fluoro-2-deoxy-D-glucose-positron emission tomography/X-ray CT(FDG PET/CT) with surgical specimens immunohistochemistry(IHC). We report a patient with abnormal FDG PET/CT in thyroid and lung, this unusual presentation may lead to misdiagnosis without surgical specimens IHC. CASE PRESENTATION: A 56-year-old man with coughing three months. FDG PET/CT was performed, and resection specimens of lung and thyroid were detected by hematoxylin eosin staining (HE) and IHC. PET/CT: lung tumor SUVmax: 3.69, delay: 5.17; and thyroid tumor SUVmax 19.97. HE reveal papillary adenocarcinoma, but histological differentiation of primary pulmonary adenocarcinoma from metastatic adenocarcinoma is sometimes difficult because of their phenotypic similarities. So IHC was performed, the IHC of lung tumor: cytokeratin 20 (CK20)-, thyroglobulin(Tg)-, cytokeratin7(CK7)+, thyroid transcription factor-1 (TTF-1)+; thyroid tumor: CK7+, TTF-1+, thyroglobulin+, CK20-. Therefore, the final diagnosis was double primary adenocarcinomas of thyroid and lung. CONCLUSION: FDG PET/CT has preliminary diagnostic capacity of multiple primary tumors; the final diagnosis should be adopted for specimens after tumor-specific markers IHC to obtain. Consequently, effective therapeutic approaches can be designed and conducted. PMID- 21974802 TI - Foxp3 inhibits HDAC1 activity to modulate gene expression in human T cells. AB - We have previously reported that HIV-1 preferentially infects Foxp3+ Treg cells in vitro and in vivo, and Foxp3 enhances the HIV-1 LTR expression through epigenetic mechanisms in T cells. We report here that histone deacetylase inhibitor (HDACi) failed to further enhance HIV gene expression in FoxP3+ T cells. We discovered that Foxp3 inhibited cellular HDAC activity in T cells, and mutations in the forkhead domain that ablate Foxp3 function also abolished its ability to inhibit HDAC. When co-expressed, Foxp3 specifically inhibited the deacetylase activity of HDAC1. We further showed that Foxp3 was associated with HDAC1, and mutations in the forkhead domain that ablate Foxp3 function in Treg cells also inhibited Foxp3 association with and inhibition of HDAC1. Finally, Foxp3 failed to enhance HIV-1 gene expression in human T cells expressing HDAC1 specific shRNA. We conclude that Foxp3 modulates gene expression in human T cells at least partly by inhibiting HDAC1 activity. PMID- 21974803 TI - Decoding bacteriophage P22 assembly: identification of two charged residues in scaffolding protein responsible for coat protein interaction. AB - Proper assembly of viruses must occur through specific interactions between capsid proteins. Many double-stranded DNA viruses and bacteriophages require internal scaffolding proteins to assemble their coat proteins into icosahedral capsids. The 303 amino acid bacteriophage P22 scaffolding protein is mostly helical, and its C-terminal helix-turn-helix (HTH) domain binds to the coat protein during virion assembly, directing the formation of an intermediate structure called the procapsid. The interaction between coat and scaffolding protein HTH domain is electrostatic, but the amino acids that form the protein protein interface have yet to be described. In the present study, we used alanine scanning mutagenesis of charged surface residues of the C-terminal HTH domain of scaffolding protein. We have determined that P22 scaffolding protein residues R293 and K296 are crucial for binding to coat protein and that the neighboring charges are not essential but do modulate the affinity between the two proteins. PMID- 21974804 TI - Adjuvant effect of a natural TLR4 ligand on dendritic cell-based cancer immunotherapy. AB - The clinical efficacy of dendritic cell (DC) vaccine in cancer patients has been unsatisfactory due, at least in part, to the deficiency of maturation and impaired migration of ex vivo generated DCs to the draining lymph nodes. To solve this problem, we used angelan, a natural TLR4 ligand, to enhance the maturation and migration of DCs. Angelan increased the expression of MHC-I/II, CD80, and CD86, DC maturation markers, through the NF-kappaB pathway. This compound also increased CCR7 expression in DCs through NF-kappaB and p38 pathway and enhanced their migration against CCL19, which is a key chemokine that guides DCs into lymph nodes. We also showed that angelan enhanced in vivo DC homing from tissues to draining lymph nodes. When treated to DCs in vitro and vivo, angelan increased antitumor activity of DCs in B16F10 syngeneic tumor model. Taken together, the present data suggest that a natural TLR4 ligand might be helpful for overcoming the disadvantages of DC-based cancer therapy, such as impaired maturation and poor migration in cancer patients. PMID- 21974805 TI - Galectin-3--a jack-of-all-trades in cancer. AB - Galectin-3 is a mammalian beta-galactoside-binding protein that is expressed by various types of human cells. Changes in galectin-3 expression and subcellular and intercellular localizations are commonly seen in cancer and pre-cancerous conditions. It is increasingly recognized that galectin-3 is an important regulator of a broad range of cancer cell activities and plays important roles in cancer cell growth, transformation, apoptosis, angiogenesis, adhesion, invasion and metastasis. Such a divergent influence of galectin-3 on cancer cell activities derives from its multiple inter- and sub-cellular localizations where it interacts with a range of different binding partners. This mini-review summaries the diverse influences of galectin-3 on cancer cell behaviours with particular emphasis on its role in tumorigenesis and metastasis. PMID- 21974806 TI - Inhibition of Akt/FOXO3a signaling by constitutively active FOXO3a suppresses growth of follicular thyroid cancer cell lines. AB - Akt-dependent FOXO3a cytoplasmic translocation is an important tumorigenic mechanism for escaping from apoptosis in cancer cells. In the present study, we examined whether non-phosphorylatable FOXO3a can inhibit cell growth of various follicular thyroid carcinoma (FTC) cell lines. Adenovirus carrying the FOXO3a triple mutant (TM) sequence including point mutations at three Akt phosphorylation sites (Ad-FOXO3a-TM) was generated and transduced to the cells to mimic inhibition of Akt/FOXO3a signal. Transduction of Ad-FOXO3a-TM to FTC133 cells induced cell cycle arrest and apoptosis. Injection of Ad-FOXO3a-TM suppressed the growth of xenograft tumors in athymic mice. Consequently, our results indicate that gene therapy based on Ad-FOXO3a-TM has therapeutic potential for FTC. PMID- 21974807 TI - Segmentation of epithelium in H&E stained odontogenic cysts. AB - An algorithm for the automated segmentation of epithelial tissue in digital images of histologic tissue sections of odontogenic cysts (cysts originating from residual odontogenic epithelium) is presented. The algorithm features an image standardization process that greatly reduces variation in luminance and chrominance between images due to variations in sample preparation. Segmentation of the epithelial regions of images uses an algorithm based on binary graph cuts where graph weights depend on probabilities obtained from colour histogram models of epithelium and stroma image regions. Algorithm training used a data set of 38 images of four types of odontogenic cyst and was tested using a separate data set of 35 images of the same four cyst types. The best parameters for the segmentation algorithm were determined using a response-surface optimizer. The best parameter set resulted in an overall mean (+/- std. dev.) sensitivity of 91.5 +/- 17% and overall mean specificity of 85.1 +/- 18.6% on the training set. Particularly good results were obtained for dentigerous and odontogenic keratocysts for which the mean sensitivities/specificities were 91.9 +/- 6.15%/97.4 +/- 2.15% and 96.1 +/- 1.98%/98.7 +/- 3.16%, respectively. Our method is potentially applicable to many pathological conditions in similar tissues, such as skin and mucous membranes where there is a clear microscopic distinction between epithelium and connective tissues. PMID- 21974808 TI - Quality of life, functional ability and physical activity after different surgical interventions for bone cancer of the leg: A systematic review. AB - PURPOSE: To systematically review published studies comparing Quality of Life (QoL), functional ability and/or physical activity between different surgical interventions due to a malignant bone tumour of the leg. METHODS: A systematic literature search, covering the years 2000-2010 was performed using the PubMed, Embase, Web of science and Cochrane databases. Studies were included if they described and statistically compared QoL, functional ability and/or physical activity of at least two surgical interventions for lower extremity bone cancer. In addition, the methodological quality of the selected studies was evaluated by using a 24-point scale. Where appropriate, a qualitative analysis or meta analysis was performed. RESULTS: The search strategy resulted in a list of 246 citations. Based on titles and abstracts 50 full-text articles were selected, of which 13 articles describing 12 studies, were finally included. Overall, the methodological quality of the studies was moderate. Studies were heterogeneous with respect to their categorisation of surgical interventions, average age of patients and average duration of follow-up. Overall, results regarding differences between ablative and limb-sparing surgery varied largely. Meta analysis was considered to be not appropriate due to clinical heterogeneity, methodological differences and flaws. CONCLUSION: Twelve studies comparing the outcomes of QoL, functional ability and physical activity between limb-sparing and ablative surgery groups were identified, with an overall moderate methodological quality. Their largely varying outcomes suggest that no general conclusions on the advantage of either limb-sparing or ablative surgery in patients with malignant bone tumours of the lower extremity can be drawn. PMID- 21974809 TI - Cytotoxic properties of Adamantyl isothiocyanate and potential in vivo metabolite adamantyl-N-acetylcystein in gynecological cancer cells. AB - This study determined the in vitro potential of novel compounds adamantyl-N acetylcystein and adamantyl isothiocyanate to treat gynecological cancers. Adamantyl-N-acetylcystein is postulated to be an in vivo metabolite of adamantyl isothiocyanate as dietary isothiocyanates are converted to N-acetylcysteine conjugates. A viability assay suggested that adamantyl isothiocyanate and adamantyl-N-acetylcystein are cytotoxic to cancer cells including gynecological cell lines. A NCI60 cancer cell assay revealed that growth-inhibition and cytotoxicity of adamantyl-N-acetylcystein were cell line, but not tissue type specific. Cell cycle studies revealed that adamantyl-N-acetylcystein and adamantyl isothiocyanate arrest SKOV-3 ovarian cancer cells in G2/M phase. By TUNEL, immunoblotting, and viability studies employing caspase and p38 mitogen activated protein kinase inhibitors, we proved that reduction in SKOV-3 viability is a consequence of DNA fragmentation and apoptosis. Cytotoxic action of adamantyl-N-acetylcystein in SKOV-3 and endometrial cancer (ECC-1, RL95-2, AN3CA, and KLE) cells required excess generation of reactive oxygen species which could be blocked by antioxidant co-treatment. Adamantyl-N-acetylcystein treatment led to modified expression or activation of apoptotic and oncogenic proteins such as JNK/SAPK, AKT, XIAP, and EGF-R for SKOV-3 and JNK/SAPK and ERK1/2 for ECC-1 cells. We suggest the further development of adamantyl-N-acetylcystein by sensitizing cells to the drug using signaling inhibitors or redox-modulating agents and by evaluating the drug efficacy in ovarian and endometrial in-vivo tumor models. PMID- 21974810 TI - Structural analysis of hubs in human NR-RTK network. AB - BACKGROUND: Currently a huge amount of protein-protein interaction data is available therefore extracting meaningful ones are a challenging task. In a protein-protein interaction network, hubs are considered as key proteins maintaining function and stability of the network. Therefore, studying protein protein complexes from a structural perspective provides valuable information for predicted interactions. RESULTS: In this study, we have predicted by comparative modelling and docking methods protein-protein complexes of hubs of human NR-RTK network inferred from our earlier study. We found that some interactions are mutually excluded while others could occur simultaneously. This study revealed by structural analysis the key role played by Estrogen receptor (ESR1) in mediating the signal transduction between human Receptor Tyrosine kinases (RTKs) and nuclear receptors (NRs). CONCLUSIONS: Although the methods require human intervention and judgment, they can identify the interactions that could occur together or ones that are mutually exclusive. This adds a fourth dimension to interaction network, that of time, and can assist in obtaining concrete predictions consistent with experiments. PMID- 21974811 TI - A plant-based system for rapid production of influenza vaccine antigens. AB - BACKGROUND: Influenza virus is a globally important respiratory pathogen that causes a high degree of annual morbidity and mortality. Significant antigenic drift results in emergence of new, potentially pandemic, virus variants. The best prophylactic option for controlling emerging virus strains is to manufacture and administer pandemic vaccines in sufficient quantities and to do so in a timely manner without impacting the regular seasonal influenza vaccine capacity. Current, egg-based, influenza vaccine production is well established and provides an effective product, but has limited capacity and speed. OBJECTIVES: To satisfy the additional global demand for emerging influenza vaccines, high-performance cost-effective technologies need to be developed. Plants have a potential as an economic and efficient large-scale production platform for vaccine antigens. METHODS: In this study, a plant virus-based transient expression system was used to produce hemagglutinin (HA) proteins from the three vaccine strains used during the 2008-2009 influenza season, A/Brisbane/59/07 (H1N1), A/Brisbane/10/07 (H3N2), and B/Florida/4/06, as well as from the recently emerged novel H1N1 influenza A virus, A/California/04/09. RESULTS: The recombinant plant-based HA proteins were engineered and produced in Nicotiana benthamiana plants within 2 months of obtaining the genetic sequences specific to each virus strain. These antigens expressed at the rate of 400-1300 mg/kg of fresh leaf tissue, with >70% solubility. Immunization of mice with these HA antigens induced serum anti-HA IgG and hemagglutination inhibition antibody responses at the levels considered protective against these virus infections. CONCLUSIONS: These results demonstrate the feasibility of our transient plant expression system for the rapid production of influenza vaccine antigens. PMID- 21974812 TI - A prospective study of catheter-related complications in HPN patients. AB - BACKGROUND & AIMS: Central venous access device (CVAD)-related complications such as catheter-related sepsis, occlusion and breakage contribute to both mortality and morbidity in home parenteral nutrition (HPN) patients. Prospectively collected data in these patients are scarce. METHODS: Data on all CVAD-related complications in four tertiary referral centres in Australia and New Zealand were prospectively collected between 01/01/2009 and 31/12/2009 together with costs of each episode that required admission. RESULTS: Of 53 patients (42 adults and 11 children), 27 suffered a total of 49 episodes of CVAD-associated complications (line infection 36, catheter blockage 5, line fracture 1, line migration 7), giving an incidence of 3.6 per 1000 CVAD days (11.6 per 1000 in patients with a multi-use CVAD). Thirty seven episodes resulted in hospital admission for a median duration of 8 days (range 1-29). Responsible microbes were mainly enteric with klebsiella being the most commonly isolated organism (10 episodes). The average cost of care per episode of CVAD-associated complication requiring inpatient admission was $A9,710 (?6480 approximately). CONCLUSION: CVAD complications, in particular line infection are still a major source of potentially avoidable HPN morbidity and mortality with a high cost to the healthcare system. The predominance of enteric organisms in our series raises the possibility of bacterial translocation as a significant component of the pathogenesis of line sepsis in HPN patients. PMID- 21974813 TI - Insulin secretion, nutritional status and respiratory function in cystic fibrosis patients with normal glucose tolerance. AB - BACKGROUND & AIMS: Impaired growth and nutritional status in CF may be related to progressive insulin deficiency before CF-Related Diabetes has established. Aim of this study was to analyse the association of circulating insulin with nutritional status and lung function in CF patients with normal glucose tolerance (NGT). METHODS: We performed OGTT in 152 consecutive CF patients aged 8-20 years: 115 of them had NGT and were included in the study. Areas under the curves (AUC) of glucose, insulin and c-peptide after 120 min were calculated. Quartiles (Q) of increasing fasting insulin (fINS-Q) and c-peptide (fCP-Q) levels were calculated in CF patients. Respiratory function parameters (FEV1, FVC), Standard Deviation Scores (SDS) of height, weight and BMI were compared between Q1 and the three higher Q. Multiple regression analysis was used to analyse the association of fasting insulin, c-peptide or OGTT derived indices with nutritional or respiratory parameters. RESULTS: Compared to patients in fINS-Q4 or fCP-Q4, those in fINS-Q1 or in fCP-Q1 respectively showed lower levels of insulin AUC or c peptide AUC (both P < 0.0001), weight-SDS (P = 0.013, P = 0.007), BMI-SDS (P = 0.010, P = 0.002), FEV1 (P = 0.076, P = 0.013) and FVC (P = 0.101, P = 0.009). Age- and gender-adjusted regression analysis showed significant associations of fINS and fCP with SDS of BMI (P = 0.023 and P = 0.001 respectively), fCP was significant associated with FEV1 (P = 0.01). AUC insulin/AUC glucose ratio (P < 0.0001) and AUC c-peptide/AUC glucose ratio (P = 0.0001) were significantly associated with FEV1. CONCLUSIONS: Insulin deficiency in CF patients with NGT has a significant impact on clinical outcomes. PMID- 21974814 TI - Single-center experience with levosimendan in children undergoing cardiac surgery and in children with decompensated heart failure. AB - BACKGROUND: Levosimendan has pharmacologic and hemodynamic advantages over conventional intravenous inotropic agents. It has been used mainly as a rescue drug in the pediatric intensive care unit or in the operating room. We present the largest single-center experience of levosimendan in children. METHODS: Retrospective analysis of all children who received levosimendan infusions between July 5, 2001 and July 4, 2010 in a pediatric intensive care unit. The results of a questionnaire for physicians (anesthesiologist/intensivists, cardiologists and cardiac surgeons) concerning their clinical perceptions of levosimendan are evaluated RESULTS: During the study period a total of 484 infusions were delivered to 293 patients 53% of whom were male. The median age of the patients was 0.4 years (4 hours-21.1 years) at the time of levosimendan administration. A majority of levosimendan infusions were administered to children who were undergoing cardiac surgery (72%), 14% to children with cardiomyopathy and 14% to children with cardiac failure. Eighty-nine out of the 293 patients (30.4%) received repeated doses of levosimendan (up to 11 infusions). The most common indication for the use of levosimendan (94%) was when the other inotropic agents were insufficient to maintain stable hemodynamics. Levosimendan was especially used in children with cardiomyopathy (100%) or with low cardiac output syndrome (94%). A majority (89%) of the respondents believed that levosimendan administration postponed the need for mechanical assist devices in some children with cardiomyopathy. Moreover, 44% of respondents thought that the mechanical support was totally avoided in some patients undergoing cardiac surgery after receiving levosimendan. CONCLUSION: Levosimendan is widely used in our institution and many physicians believe that its use could decrease the need for mechanical support in children undergoing cardiac surgery or in children with decompensated heart failure. However, there is a lack of good empirical evidence in children to support this perception. PMID- 21974815 TI - Molecular epidemiology of avian influenza viruses circulating among healthy poultry flocks in farms in northern Vietnam. AB - Repeated epizootics of highly pathogenic avian influenza (HPAI) virus subtype H5N1 were reported from 2003 to 2005 among poultry in Vietnam. More than 200 million birds were killed to control the spread of the disease. Human cases of H5N1 infection have been sporadically reported in an area where repeated H5N1 outbreaks among birds had occurred. Subtype H5N1 strains are established as endemic among poultry in Vietnam, however, insights into how avian influenza viruses including the H5N1 subtype are maintained in endemic areas is not clear. In order to determine the prevalence of different avian influenza viruses (AIVs), including H5N1 circulating among poultry in northern Vietnam, surveillance was conducted during the years 2006-2009. A subtype H5N1 strain was isolated from an apparently healthy duck reared on a farm in northern Vietnam in 2008 and was identified as an HPAI. Although only one H5N1 virus was isolated, it supports the view that healthy domestic ducks play a pivotal role in maintaining and transmitting H5N1 viruses which cause disease outbreaks in northern Vietnam. In addition, a total of 26 AIVs with low pathogenicity were isolated from poultry and phylogenetic analysis of all the eight gene segments revealed their diverse genetical backgrounds, implying that reassortments have occurred frequently among strains in northern Vietnam. It is, therefore, important to monitor the prevalence of influenza viruses among healthy poultry between epidemics in an area where AIVs are endemic. PMID- 21974816 TI - Spatial differences in occurrence of paratuberculosis in Danish dairy herds and in control programme participation. AB - Paratuberculosis is a chronic infection of economic importance to the cattle industry and a voluntary control programme is offered to Danish dairy farmers. Our objective was to evaluate spatial differences in both control programme participation and paratuberculosis prevalence in Denmark. The study included 4414 dairy herds: 1249 were participating in the control programme, and 1503 were tested for antibodies to Mycobacterium avium subsp. paratuberculosis (MAP). Spatial differences were evaluated by kernel smoothing, kriging, and cluster analysis. Participation was lowest among herds on the island Zealand (<=23%). The risk of a herd being infected with MAP was found to be high on most of Zealand, but the uncertainty of this result was large due to a limited number of tested herds. In the rest of the country, the south western part of the peninsula Jutland had the highest risk of MAP (>=91%). The risk of MAP was also high (86 91%) in the northern part of both Jutland and Funen. The predicted apparent within-herd prevalence was highest (5-8.5%) in some local areas across Jutland, in the north western part of the island Funen, and in the south and western part of Zealand. Scan statistics located the primary cluster of herds with high apparent within-herd prevalence in the western part of Funen. Furthermore, a number of significant clusters were found in Jutland and a single significant cluster in Zealand. Consistency was found between kriging and scan statistics results with respect to location of areas with high apparent within-herd prevalence of MAP. Potential explanations for differences in participation include herd size and local herd health advisers, whereas for example soil characteristics might influence prevalence. Further studies are needed to evaluate these and other risk factors. PMID- 21974817 TI - The development of pistillate and perfect florets in Xeranthemum squarrosum (Asteraceae). AB - The formation of capitulum inflorescence with two different types of floret is an interesting issue in floral biology and evolution. Here we studied the inflorescence, floral ontogeny and development of the everlasting herb, Xeranthemum squarrosum, using epi-illumination microscopy. The small vegetative apex enlarged and produced involucral bracts with helical phyllotaxy, which subtended floret primordia in the innermost whorl. Initiation of floret primordia was followed by an acropetal sequence, except for pistillate peripheral florets. The origin of receptacular bracts was unusual, as they derived from the floral primordia rather than the receptacular surface. The order of whorl initiation in both disc and pistillate flowers included corolla, androecium and finally calyx, together with the gynoecium. The inception of sepals and stamens occurred in unidirectional order starting from the abaxial side, whereas petals incepted unidirectionally from the adaxial or abaxial side. Substantial differences were observed in flower structure and the development between pistillate and perfect florets. Pistillate florets presented a zygomorphic floral primordium, tetramerous corolla and androecium and two sepal lobes. In these florets, two sepal lobes and four stamen primordia stopped growing, and the ovary developed neither an ovule nor a typical stigma. The results suggest that peripheral pistillate florets in X. squarrosum, which has a bilabiate corolla, could be considered as an intermediate state between ancestral bilabiate florets and the derived ray florets. PMID- 21974819 TI - [In Process Citation]. PMID- 21974820 TI - [Not Available]. AB - Traditionally, the orthodontists evaluate the modifications made by the general growth of the face by superimposing "as well as possible" (best fit) the serial head-films of beginning and end of treatment on easily locatable anatomical points of the cranial base. Many authors showed that this evaluation method of the development of the facial skeleton is vague and thus generator of considerable errors of appreciation. The process of superimposition of profile head-films on stable structures of the former base of cranium rests primarily on the observation made by De Coster in 1952 on "the immutability of the basi cranial line", confirmed histologically by Melsen in 1971. In 1972, the longitudinal studies undertaken by Bjork and Skieller using metal implants on more than 200 cases highlighted the stability of certain anatomical structures within the maxilla and the mandible. The "Structural Method" of general and local superimpositions, thus developed starting from these discoveries, brought a new vision of the different facial growth patterns and allowed a greater comprehension of the effectiveness of the orthodontic techniques. PMID- 21974818 TI - Identification of the estrogen receptor GPER in neoplastic and non-neoplastic human testes. AB - BACKGROUND: Estrogen signaling is mediated by estrogen receptor beta isoforms in normal and neoplastic human testes. Recently, a G-protein-coupled-receptor (GPER) has been suggested as being involved in rapid responses to estrogens in different normal and tumor cells. METHODS: This study investigated the GPER expression in paraffin-embedded samples from non neoplastic and neoplastic human testes (sex cord stromal and germ cell tumors) by immunohistochemical and Western Blot analyses. RESULTS: In control testes, a positive GPER immunoreactivity was detected in Leydig and in Sertoli cells while all germ cells were immunonegative. Furthermore, neoplastic cells of the Sertoli cell tumor, Leydig cell tumor, seminoma and embryonal carcinoma samples were all immunopositive. The immunoblots of testis extracts confirmed the results. CONCLUSIONS: These findings suggest that GPER could mediate estrogen signaling in both normal and transformed somatic cells of human testis, but they reveal a differential expression of the novel estrogen receptor in non neoplastic and neoplastic germ cells. PMID- 21974821 TI - [Not Available]. AB - This cephalometric study evaluates the stability of skeletal and dento-alveolar changes after 6 to 9 months of early orthodontic treatment of Class II malocclusions with the Distal Active Concept (DAC). An analysis of the results showed significant skeletal changes, notably an average of 8.5 mm of mandibular growth, which remained stable after the close of treatment. However, the correction of the maxillary incisal protrusion relapsed slightly. The treatment provoked lower incisal labial inclination proved to be temporary, with the lower anterior teeth returning to their initial position at the close of the 30-month post-treatment observation period. PMID- 21974822 TI - [Not Available]. AB - Most of dentofacial abnomalies are due to mandibular retrognathisms. These abnomalies are surgically treated mostly by mandibular lenghtening with the help of the sagittal split osteotomy although other procedures could be used. Mandibular distraction and advancement of the receding lower jaw by retrocondylar cartilagenous graft are the two main alternatives. The retrocondylar cartilagenous graft has been introduced by Leon Dufourmentel in 1929. This procedure has strong anatomical and physiological basis and has to be better known because it is effective and respects the temporo-mandibular joint. The permanent advancement of the mandible is assured by a retrocondylar graft placed in the pretympanal and extra-articular space located between tympanal bone and retrocondylar venous plexus. All the mandibule retrognathisms should be treated through this approach, especially with associated obstruction sleep apnea syndrome. PMID- 21974823 TI - [Not Available]. AB - The ICON (Index of Complexity, Outcome and Need) is a new index based on the consensus opinion of 97 European and American orthodontists. It records orthodontics treatment need on the basis of 5 components i.e. crossbite, upper arch crowding/spacing, buccal segment antero-posterior relationship and anterior vertical relationship. This index can be used in epidemiological studies and by public services and third party co-payment for the determination of those patients who may be eligible for public funding or reimbursement of fees. PMID- 21974824 TI - [In Process Citation]. PMID- 21974825 TI - Ileosigmoid fistula and delayed ileal obstruction secondary to blunt abdominal trauma: a case report. AB - INTRODUCTION: Abdominal trauma is a source of significant mortality and morbidity. Bowel injury as a result of blunt abdominal trauma is usually evident within hours or days of the accident. CASE PRESENTATION: A 38-year-old Caucasian Greek man presented with a subtle and delayed small bowel obstruction caused by a post-traumatic ileosigmoid fistula and ileal stricture four months after a road traffic accident. CONCLUSION: Delayed occurrence of post-traumatic small bowel stricture and ileosigmoid fistula is an uncommon surgical emergency. General surgeons as well as emergency physicians should bear this manifestation in mind should a patient return to the hospital several weeks or even years after blunt abdominal trauma with symptoms or signs of bowel obstruction. PMID- 21974826 TI - ICSH recommendations for the measurement of haemoglobin A2. AB - Although DNA analysis is needed for characterization of the mutations that cause beta-thalassaemia, measurement of the Hb A(2) is essential for the routine identification of people who are carriers of beta-thalassaemia. The methods of quantitating Hb A(2) are described together with pitfalls in undertaking these laboratory tests with particular emphasis on automated high-performance liquid chromatography and capillary electrophoresis. PMID- 21974827 TI - Anthropometrically determined nutritional status of urban primary schoolchildren in Makurdi, Nigeria. AB - BACKGROUND: No information exists on the nutritional status of primary school children residing in Makurdi, Nigeria. It is envisaged that the data could serve as baseline data for future studies, as well as inform public health policy. The aim of this study was to assess the prevalence of malnutrition among urban school children in Makurdi, Nigeria. METHODS: Height and weight of 2015 (979 boys and 1036 girls), aged 9-12 years, attending public primary school in Makurdi were measured and the body mass index (BMI) calculated. Anthropometric indices of weight-for-age (WA) and height-for-age (HA) were used to estimate the children's nutritional status. The BMI thinness classification was also calculated. RESULTS: Underweight (WAZ < -2) and stunting (HAZ < -2) occurred in 43.4% and 52.7%, respectively. WAZ and HAZ mean scores of the children were -0.91(SD = 0.43) and 0.83 (SD = 0.54), respectively. Boys were more underweight (48.8%) than girls (38.5%), and the difference was statistically significant (p = 0.024; p < 0.05). Conversely, girls tend to be more stunted (56.8%) compared to boys (48.4%) (p = 0.004; p < 0.05). Normal WAZ and HAZ occurred in 54.6% and 44.2% of the children, respectively. Using the 2007 World Health Organisation BMI thinness classification, majority of the children exhibited Grade 1 thinness (77.3%), which was predominant at all ages (9-12 years) in both boys and girls. Gender wise, 79.8% boys and 75.0% girls fall within the Grade I thinness category. Based on the WHO classification, severe malnutrition occurred in 31.3% of the children. CONCLUSIONS: There is severe malnutrition among the school children living in Makurdi. Most of the children are underweight, stunted and thinned. As such, providing community education on environmental sanitation and personal hygienic practices, proper child rearing, breast-feeding and weaning practices would possibly reverse the trends. PMID- 21974828 TI - Evolution of vacuolar proton pyrophosphatase domains and volutin granules: clues into the early evolutionary origin of the acidocalcisome. AB - BACKGROUND: Volutin granules appear to be universally distributed and are morphologically and chemically identical to acidocalcisomes, which are electron dense granular organelles rich in calcium and phosphate, whose functions include storage of phosphorus and various metal ions, metabolism of polyphosphate, maintenance of intracellular pH, osmoregulation and calcium homeostasis. Prokaryotes are thought to differ from eukaryotes in that they lack membrane bounded organelles. However, it has been demonstrated that as in acidocalcisomes, the calcium and polyphosphate-rich intracellular "volutin granules (polyphosphate bodies)" in two bacterial species, Agrobacterium tumefaciens, and Rhodospirillum rubrum, are membrane bound and that the vacuolar proton-translocating pyrophosphatases (V-H+PPases) are present in their surrounding membranes. Volutin granules and acidocalcisomes have been found in organisms as diverse as bacteria and humans. RESULTS: Here, we show volutin granules also occur in Archaea and are, therefore, present in the three superkingdoms of life (Archaea, Bacteria and Eukarya). Molecular analyses of V-H+PPase pumps, which acidify the acidocalcisome lumen and are diagnostic proteins of the organelle, also reveal the presence of this enzyme in all three superkingdoms suggesting it is ancient and universal. Since V-H+PPase sequences contained limited phylogenetic signal to fully resolve the ancestral nodes of the tree, we investigated the divergence of protein domains in the V-H+PPase molecules. Using Protein family (Pfam) database, we found a domain in the protein, PF03030. The domain is shared by 31 species in Eukarya, 231 in Bacteria, and 17 in Archaea. The universal distribution of the V H+PPase PF03030 domain, which is associated with the V-H+PPase function, suggests the domain and the enzyme were already present in the Last Universal Common Ancestor (LUCA). CONCLUSION: The importance of the V-H+PPase function and the evolutionary dynamics of these domains support the early origin of the acidocalcisome organelle. In particular, the universality of volutin granules and presence of a functional V-H+PPase domain in the three superkingdoms of life reveals that the acidocalcisomes may have appeared earlier than the divergence of the superkingdoms. This result is remarkable and highlights the possibility that a high degree of cellular compartmentalization could already have been present in the LUCA. PMID- 21974829 TI - Long-term monitoring of live cell proliferation in presence of PVP-Hypericin: a new strategy using ms pulses of LED and the fluorescent dye CFSE. AB - During fluorescent live cell imaging it is critical to keep excitation light dose as low as possible, especially in the presence of photosensitizer drugs, which generate free radicals upon photobleaching. During fluorescent imaging, stress by excitation and free radicals induces serious cell damages that may arrest the cell cycle. This limits the usefulness of the technique for drug discovery, when prolonged live cell imaging is necessary. This paper presents a strategy to provide gentle experimental conditions for dynamic monitoring of the proliferation of human lung epithelial carcinoma cells (A549) in the presence of the photosensitizer Polyvinylpyrrolidone-Hypericin. The distinctive strategy of this paper is based on the stringent environmental control and optimizing the excitation light dose by (i) using a low-power pulsed blue light-emitting diode with short pulse duration of 1.29 ms and (ii) adding a nontoxic fluorescent dye called carboxyfluorescein-diacetate-succinimidyl-ester (CFSE) to improve the fluorescence signals. To demonstrate the usefulness of the strategy, fluorescence signals and proliferation of dual-marked cells, during 5-h fluorescence imaging under pulsed excitation, were compared with those kept under continuous excitation and nonmarked reference cells. The results demonstrated 3% cell division and 2% apoptosis due to pulsed excitation compared to no division and 85% apoptosis under the continuous irradiation. Therefore, our strategy allows live cell imaging to be performed over longer time scales than with conventional continuous excitation. PMID- 21974830 TI - Study protocol: the empirical investigation of methods to correct for measurement error in biobanks with dietary assessment. AB - BACKGROUND: The Public Population Project in Genomics (P3G) is an organisation that aims to promote collaboration between researchers in the field of population based genomics. The main objectives of P3G are to encourage collaboration between researchers and biobankers, optimize study design, promote the harmonization of information use in biobanks, and facilitate transfer of knowledge between interested parties. The importance of calibration and harmonisation of methods for environmental exposure assessment to allow pooling of data across studies in the evaluation of gene-environment interactions has been recognised by P3G, which has set up a methodological group on calibration with the aim of; 1) reviewing the published methodological literature on measurement error correction methods with assumptions and methods of implementation; 2) reviewing the evidence available from published nutritional epidemiological studies that have used a calibration approach; 3) disseminating information in the form of a comparison chart on approaches to perform calibration studies and how to obtain correction factors in order to support research groups collaborating within the P3G network that are unfamiliar with the methods employed; 4) with application to the field of nutritional epidemiology, including gene-diet interactions, ultimately developing a inventory of the typical correction factors for various nutrients. METHODS/DESIGN: Systematic review of (a) the methodological literature on methods to correct for measurement error in epidemiological studies; and (b) studies that have been designed primarily to investigate the association between diet and disease and have also corrected for measurement error in dietary intake. DISCUSSION: The conduct of a systematic review of the methodological literature on calibration will facilitate the evaluation of methods to correct for measurement error and the design of calibration studies for the prospective pooling of biobanks. This could increase the efficiency of the design of such studies, improve statistical power, reduce bias, and aid in the assessment of gene-environment interaction effects in complex diseases. The systematic review of calibration of dietary intake information could inform gene-diet interaction investigations involving the pooling of results from studies with nutritional data collected in different ways. PMID- 21974831 TI - The effects of performance appraisal in the Norwegian municipal health services: a case study. AB - INTRODUCTION: Previous research in performance appraisal (PA) indicates that variation exists in learning and job motivation from performance appraisal between occupational groups. This research evaluates the potential effect of job motivation, learning and self-assessment through performance appraisals for health personnel. CASE DESCRIPTION: This article focuses on goal-setting, feedback, participation and training in performance appraisals in municipal health services in Norway; and job motivation, learning and self-assessment of performance are the dependent factors. Questionnaires were distributed to a representative sample of 600 health personnel from the Norwegian municipal health service, with a response rate of 62%. Factor analysis and regression analysis were run in SPSS 12. DISCUSSION AND EVALUATION: The study suggests that respondents learn from performance appraisal. Nurses experienced some higher job motivation from performance appraisal than auxiliary nurses. All subordinates perceived higher job motivation after performance appraisal than managers. CONCLUSION: Useful feedback, active participation and higher education are fundamental elements of discussion in performance appraisal, as well as the role of increasing employees' job motivation. In this study, nurses' job motivation seems to be more effected by PA, than for auxiliary nurses. Both nurses and auxiliary nurses indicate that there is a learning effect from PA. This study may be of interest to health researchers and managers in municipal health services. PMID- 21974833 TI - Novel primers for complete mitochondrial cytochrome b gene sequencing in mammals. AB - Sequence-based species identification relies on the extent and integrity of sequence data available in online databases such as GenBank. When identifying species from a sample of unknown origin, partial DNA sequences obtained from the sample are aligned against existing sequences in databases. When the sequence from the matching species is not present in the database, high-scoring alignments with closely related sequences might produce unreliable results on species identity. For species identification in mammals, the cytochrome b (cyt b) gene has been identified to be highly informative; thus, large amounts of reference sequence data from the cyt b gene are much needed. To enhance availability of cyt b gene sequence data on a large number of mammalian species in GenBank and other such publicly accessible online databases, we identified a primer pair for complete cyt b gene sequencing in mammals. Using this primer pair, we successfully PCR amplified and sequenced the complete cyt b gene from 40 of 44 mammalian species representing 10 orders of mammals. We submitted 40 complete, correctly annotated, cyt b protein coding sequences to GenBank. To our knowledge, this is the first single primer pair to amplify the complete cyt b gene in a broad range of mammalian species. This primer pair can be used for the addition of new cyt b gene sequences and to enhance data available on species represented in GenBank. The availability of novel and complete gene sequences as high-quality reference data can improve the reliability of sequence-based species identification. PMID- 21974832 TI - The enhancement of enzymatic hydrolysis of lignocellulosic substrates by the addition of accessory enzymes such as xylanase: is it an additive or synergistic effect? AB - BACKGROUND: We and other workers have shown that accessory enzymes, such as beta glucosidase, xylanase, and cellulase cofactors, such as GH61, can considerably enhance the hydrolysis effectiveness of cellulase cocktails when added to pretreated lignocellulosic substrates. It is generally acknowledged that, among the several factors that hamper our current ability to attain efficient lignocellulosic biomass conversion yields at low enzyme loadings, a major problem lies in our incomplete understanding of the cooperative action of the different enzymes acting on pretreated lignocellulosic substrates. RESULTS: The reported work assessed the interaction between cellulase and xylanase enzymes and their potential to improve the hydrolysis efficiency of various pretreated lignocellulosic substrates when added at low protein loadings. When xylanases were added to the minimum amount of cellulase enzymes required to achieve 70% cellulose hydrolysis of steam pretreated corn stover (SPCS), or used to partially replace the equivalent cellulase dose, both approaches resulted in enhanced enzymatic hydrolysis. However, the xylanase supplementation approach increased the total protein loading required to achieve significant improvements in hydrolysis (an additive effect), whereas the partial replacement of cellulases with xylanase resulted in similar improvements in hydrolysis without increasing enzyme loading (a synergistic effect). The enhancement resulting from xylanase aided synergism was higher when enzymes were added simultaneously at the beginning of hydrolysis. This co-hydrolysis of the xylan also influenced the gross fiber characteristics (for example, fiber swelling) resulting in increased accessibility of the cellulose to the cellulase enzymes. These apparent increases in accessibility enhanced the steam pretreated corn stover digestibility, resulting in three times faster cellulose and xylan hydrolysis, a seven-fold decrease in cellulase loading and a significant increase in the hydrolysis performance of the optimized enzyme mixture. When a similar xylanase-aided enhancement strategy was assessed on other pretreated lignocellulosic substrates, equivalent increases in hydrolysis efficiency were also observed. CONCLUSIONS: It was apparent that the 'blocking effect' of xylan was one of the major mechanisms that limited the accessibility of the cellulase enzymes to the cellulose. However, the synergistic interaction of the xylanase and cellulase enzymes was also shown to significantly improve cellulose accessibility through increasing fiber swelling and fiber porosity and also plays a major role in enhancing enzyme accessibility. PMID- 21974834 TI - Multi-professional clinical medication reviews in care homes for the elderly: study protocol for a randomised controlled trial with cost effectiveness analysis. AB - BACKGROUND: Evidence demonstrates that measures are needed to optimise therapy and improve administration of medicines in care homes for older people. The aim of this study is to determine the clinical and cost effectiveness of a novel model of multi-professional medication review. METHODS: A cluster randomised controlled trial design, involving thirty care homes. In line with current practice in medication reviews, recruitment and consent will be sought from general practitioners and care homes, rather than individual residents. Care homes will be segmented according to size and resident mix and allocated to the intervention arm (15 homes) or control arm (15 homes) sequentially using minimisation. Intervention homes will receive a multi-professional medication review at baseline and at 6 months, with follow-up at 12 months. Control homes will receive usual care (support they currently receive from the National Health Service), with data collection at baseline and 12 months. The novelty of the intervention is a review of medications by a multi-disciplinary team. Primary outcome measures are number of falls and potentially inappropriate prescribing. Secondary outcome measures include medication costs, health care resource use, hospitalisations and mortality. The null hypothesis proposes no difference in primary outcomes between intervention and control patients. The primary outcome variable (number of falls) will be analysed using a linear mixed model, with the intervention specified as a fixed effect and care homes included as a random effect. Analyses will be at the level of the care home. The economic evaluation will estimate the cost-effectiveness of the intervention compared to usual care from a National Health Service and personal social services perspective.The study is not measuring the impact of the intervention on professional working relationships, the medicines culture in care homes or the generic health-related quality of life of residents. DISCUSSION: This study will establish the effectiveness of a new model of multi-professional clinical medication reviews in care homes, using novel approaches to recruitment and consent. It is the first study to undertake an examination of direct patient outcomes, together with an economic analysis. TRIAL REGISTRATION: ISRCTN: ISRCTN90761620. PMID- 21974835 TI - Suppression of phase transitions in a confined rodlike liquid crystal. AB - The nematic-to-isotropic, crystal-to-nematic, and supercooled liquid-to-glass temperatures are studied in the liquid crystal 4-pentyl-4'-cyanobiphenyl (5CB) confined in self-ordered nanoporous alumina. The nematic-to-isotropic and the crystal-to-nematic transition temperatures are reduced linearly with the inverse pore diameter. The finding that the crystalline phase is completely suppressed in pores having diameters of 35 nm and below yields an estimate of the critical nucleus size. The liquid-to-glass temperature is reduced in confinement as anticipated by the model of rotational diffusion within a cavity. These results provide the pertinent phase diagram for a confined liquid crystal and are of technological relevance for the design of liquid crystal-based devices with tunable optical, thermal, and dielectric properties. PMID- 21974836 TI - Targeted versus universal prevention. a resource allocation model to prioritize cardiovascular prevention. AB - BACKGROUND: Diabetes mellitus brings an increased risk for cardiovascular complications and patients profit from prevention. This prevention also suits the general population. The question arises what is a better strategy: target the general population or diabetes patients. METHODS: A mathematical programming model was developed to calculate optimal allocations for the Dutch population of the following interventions: smoking cessation support, diet and exercise to reduce overweight, statins, and medication to reduce blood pressure. Outcomes were total lifetime health care costs and QALYs. Budget sizes were varied and the division of resources between the general population and diabetes patients was assessed. RESULTS: Full implementation of all interventions resulted in a gain of 560,000 QALY at a cost of ?640 per capita, about ?12,900 per QALY on average. The large majority of these QALY gains could be obtained at incremental costs below ?20,000 per QALY. Low or high budgets (below ?9 or above ?100 per capita) were predominantly spent in the general population. Moderate budgets were mostly spent in diabetes patients. CONCLUSIONS: Major health gains can be realized efficiently by offering prevention to both the general and the diabetic population. However, a priori setting a specific distribution of resources is suboptimal. Resource allocation models allow accounting for capacity constraints and program size in addition to efficiency. PMID- 21974837 TI - Application of latent semantic analysis for open-ended responses in a large, epidemiologic study. AB - BACKGROUND: The Millennium Cohort Study is a longitudinal cohort study designed in the late 1990s to evaluate how military service may affect long-term health. The purpose of this investigation was to examine characteristics of Millennium Cohort Study participants who responded to the open-ended question, and to identify and investigate the most commonly reported areas of concern. METHODS: Participants who responded during the 2001-2003 and 2004-2006 questionnaire cycles were included in this study (n = 108,129). To perform these analyses, Latent Semantic Analysis (LSA) was applied to a broad open-ended question asking the participant if there were any additional health concerns. Multivariable logistic regression was performed to examine the adjusted odds of responding to the open-text field, and cluster analysis was executed to understand the major areas of concern for participants providing open-ended responses. RESULTS: Participants who provided information in the open-ended text field (n = 27,916), had significantly lower self-reported general health compared with those who did not provide information in the open-ended text field. The bulk of responses concerned a finite number of topics, most notably illness/injury, exposure, and exercise. CONCLUSION: These findings suggest generalized topic areas, as well as identify subgroups who are more likely to provide additional information in their response that may add insight into future epidemiologic and military research. PMID- 21974838 TI - Pulmonary venous occlusion and death in pulmonary arterial hypertension: survival analyses using radiographic surrogates. AB - BACKGROUND: Recent studies find that a considerable number of patients with pulmonary arterial hypertension (PAH) develop fibrous obstruction of the pulmonary veins. Such obstruction more commonly accompanies connective tissue disorder (CTD)-associated PAH than idiopathic PAH. However, few researchers have gauged the risk of death involving obstruction of the pulmonary veins. METHODS: Thirty-seven patients with PAH were enrolled (18 patients, idiopathic PAH; 19 patients, CTD-associated PAH). The patients were 49 +/- 18 years and had a World Health Organization functional class of 3.2 +/- 0.6. Thickening of the interlobular septa, centrilobular ground-glass attenuation, and mediastinal adenopathy were surrogates for obstruction of the pulmonary veins, and were detected by a 16-row multidetector computed tomography scanner. RESULTS: The follow-up period was 714 +/- 552 days. Fifteen deaths occurred. Thickening of the interlobular septa, centrilobular ground-glass attenuation, and mediastinal adenopathy were found in 37.8%, 24.3%, and 16.2% of patients, respectively. Cox proportional hazard analysis revealed an increased risk of death with each radiographic surrogate (mediastinal adenopathy: p < 0.0001, hazard ratio = 13.9; thickening of interlobular septa: p < 0.001, hazard ratio = 12.0; ground-glass attenuation: p = 0.02, hazard ratio = 3.7). The statistical significance of these relationships was independent of the cause of PAH and plasma concentration of brain natriuretic peptide. CONCLUSIONS: The results of this study imply that obstruction of the pulmonary veins is associated with an increased risk of death in patients with PAH. PMID- 21974840 TI - Prevalence of hypertension and its correlates in Lusaka urban district of Zambia: a population based survey. AB - BACKGROUND: Hypertension is a leading cause for ill-health, premature mortality and disability. The objective of the study was to determine the prevalence and associated factors for hypertension in Lusaka, Zambia. METHODS: A cross sectional study was conducted. Odds ratios and their 95% confidence intervals were calculated to assess relationships between hypertension and explanatory variables. RESULTS: A total of 1928 individuals participated in the survey, of which 33.0% were males. About a third of the respondents had attained secondary level education (35.8%), and 20.6% of males and 48.6% of females were overweight or obese. The prevalence for hypertension was 34.8% (38.0% of males and 33.3% of females). In multivariate analysis, factors independently associated with hypertension were: age, sex, body mass index, alcohol consumption, sedentary lifestyle, and fasting blood glucose level. CONCLUSIONS: Health education and structural interventions to promote healthier lifestyles should be encouraged taking into account the observed associations of the modifiable risk factors. PMID- 21974841 TI - Progress in the treatment of locally advanced clinically resectable rectal cancer. AB - There have been significant developments in the adjuvant treatment of locally advanced clinically resectable (T3 and/or N+) rectal cancer. Postoperative systemic chemotherapy plus concurrent pelvic irradiation (chemoradiation) significantly improves local control and survival compared with surgery alone. The German Rectal Cancer Trial confirmed that when chemoradiation is delivered preoperatively there is a significant decrease in acute and late toxicity and a corresponding increase in local control and sphincter preservation. Despite these advances, controversies remain. Among these controversies are the role of short course radiation, whether postoperative adjuvant chemotherapy is necessary for all patients, and if the type of surgery after chemoradiation can be modified based on tumor response. Are there more accurate imaging techniques and/or molecular markers to help identify patients with positive pelvic nodes with the goal of reducing the chance of overtreatment with preoperative therapy. Will more effective systemic agents both improve outcome and modify the need for pelvic irradiation? This review examines the advances in chemoradiation as well as addresses these and other opportunities for improvement. PMID- 21974842 TI - A proposed method to investigate reliability throughout a questionnaire. AB - BACKGROUND: Questionnaires are used extensively in medical and health care research and depend on validity and reliability. However, participants may differ in interest and awareness throughout long questionnaires, which can affect reliability of their answers. A method is proposed for "screening" of systematic change in random error, which could assess changed reliability of answers. METHODS: A simulation study was conducted to explore whether systematic change in reliability, expressed as changed random error, could be assessed using unsupervised classification of subjects by cluster analysis (CA) and estimation of intraclass correlation coefficient (ICC). The method was also applied on a clinical dataset from 753 cardiac patients using the Jalowiec Coping Scale. RESULTS: The simulation study showed a relationship between the systematic change in random error throughout a questionnaire and the slope between the estimated ICC for subjects classified by CA and successive items in a questionnaire. This slope was proposed as an awareness measure--to assessing if respondents provide only a random answer or one based on a substantial cognitive effort. Scales from different factor structures of Jalowiec Coping Scale had different effect on this awareness measure. CONCLUSIONS: Even though assumptions in the simulation study might be limited compared to real datasets, the approach is promising for assessing systematic change in reliability throughout long questionnaires. Results from a clinical dataset indicated that the awareness measure differed between scales. PMID- 21974843 TI - Statin use and serum bilirubin levels. PMID- 21974846 TI - The association between cerebral atherosclerosis and arterial stiffness in acute ischemic stroke. AB - OBJECTIVE: Arterial stiffness is associated with cardiovascular risk factors and atherosclerosis. Measurement of pulse wave velocity (PWV) is one of the most representative and noninvasive techniques for assessing arterial stiffness. We investigated the association of cerebral atherosclerosis with brachial-ankle PWV (baPWV) in acute ischemic stroke patients. If present, we sought to determine whether the relationship differed between atherosclerosis in the intracranial artery and atherosclerosis in the extracranial artery. METHODS: We included 801 patients with acute ischemic stroke who had undergone angiographic study and baPWV measurement between January 2007 and May 2010. Patients with cerebral artery atherosclerosis were categorized into those with intracranial atherosclerosis, those with extracranial atherosclerosis and those with both intracranial and extracranial atherosclerosis. We determined factors that were associated with baPWV. RESULTS: Univariate and multivariate analyses showed that high baPWV was significantly associated with older age, lower body mass index, higher brachial systolic pressure, and diabetes mellitus. Increased baPWV was associated with the presence of atherosclerosis (>= 50% stenosis) in the intracranial cerebral artery as well as in both the intracranial and extracranial arteries, but not with atherosclerosis in the extracranial cerebral artery. The burden of intracranial cerebral atherosclerosis, which was assessed based on the number of arteries with atherosclerosis, was also closely associated with baPWV. CONCLUSION: Arterial stiffness was associated with the presence and burden of intracranial cerebral atherosclerosis in stroke patients, but was not associated with the extracranial cerebral atherosclerosis. These findings suggest a potential pathophysiological association between increased arterial stiffness and intracranial cerebral atherosclerosis. PMID- 21974844 TI - Free fatty acids are associated with insulin resistance but not coronary artery atherosclerosis in rheumatoid arthritis. AB - BACKGROUND: Free fatty acids (FFAs) affect insulin signaling and are implicated in the pathogenesis of insulin resistance and atherosclerosis. Inflammatory cytokines such as interleukin-6 (IL-6) increase lipolysis and thus levels of FFAs. We hypothesized that increased IL-6 concentrations are associated with increased FFAs resulting in insulin resistance and atherosclerosis in rheumatoid arthritis (RA). METHODS: Clinical variables, serum FFAs and inflammatory cytokines, homeostasis model assessment for insulin resistance (HOMA-IR), and coronary artery calcium were measured in 166 patients with RA and 92 controls. We compared serum FFAs in RA and controls using Wilcoxon rank sum tests and further tested for multivariable association by adjusting for age, race, sex and BMI. Among patients with RA, we assessed the relationship between serum FFAs and inflammatory cytokines, HOMA-IR, and coronary artery calcium scores using Spearman correlation and multivariable regression analyses. RESULTS: Serum FFAs did not differ significantly in patients with RA and controls (0.56mmol/L [0.38 0.75] and 0.56mmol/L [0.45-0.70] respectively, p=0.75). Presence of metabolic syndrome was associated with significantly increased serum FFAs in both RA and controls (p=0.035 and p=0.025). In multivariable regression analysis that adjusted for age, race, sex and BMI, serum FFAs were associated with HOMA-IR (p=0.011), CRP (p=0.01), triglycerides (p=0.005) and Framingham risk score (p=0.048) in RA, but not with IL-6 (p=0.48) or coronary artery calcium score (p=0.62). CONCLUSIONS: Serum FFAs do not differ significantly in patients with RA and controls. FFAs may contribute to insulin resistance, but are not associated with IL-6 and coronary atherosclerosis in RA. PMID- 21974847 TI - Zinc induces chemokine and inflammatory cytokine release from human promonocytes. AB - Our previous studies found that zinc oxide (ZnO) particles induced expression of intercellular adhesion molecule-1 (ICAM-1) protein in vascular endothelial cells via NF-kappaB and that zinc ions dissolved from ZnO particles might play the major role in the process. This study aimed to determine if zinc ions could cause inflammatory responses in a human promonocytic leukemia cell line HL-CZ. Conditioned media from the zinc-treated HL-CZ cells induced ICAM-1 protein expression in human umbilical vein endothelial cells (HUVEC). Zinc treatment induced chemokine and inflammatory cytokine release from HL-CZ cells. Inhibition of NFkappaB activity by over-expression of IkappaBalpha in HL-CZ cells did not block the conditioned medium-induced ICAM-1 protein expression in HUVEC cells. Zinc treatment induced activation of multiple immune response-related transcription factors in HL-CZ cells. These results clearly show that zinc ions induce chemokine and inflammatory cytokine release from human promonocytes, accompanied with activation of multiple immune response-related transcription factors. Our in vitro evidence in the zinc-induced inflammatory responses of vascular cells provides a critical linkage between zinc exposure and pathogenesis of those inflammatory vascular diseases. PMID- 21974848 TI - Simultaneous removal and evaluation of organic substrates and NH3-N by a novel combined process in treating chemical synthesis-based pharmaceutical wastewater. AB - A full-scale novel combined anaerobic/micro-aerobic and two-stage aerobic biological process is used for the treatment of an actual chemical synthesis based pharmaceutical wastewater containing amoxicillin. The anaerobic system is an up-flow anaerobic sludge blanket (UASB), the micro-aerobic system is a novel micro-aerobic hydrolysis acidification reactor (NHAR) and the two-stage aerobic process comprised cyclic activated sludge system (CASS) and biological contact oxidation tank (BCOT). The influent wastewater was high in COD, NH(3)-N varying daily 4016-13,093 mg-COD L(-1) and 156.4-650.2 mg-NH(3)-N L(-1), amoxicillin varying weekly between 69.1 and 105.4 mg-amoxicillin L(-1), respectively; Almost all the COD, NH(3)-N, amoxicillin were removed by the biological combined system, with removal percentages 97%, 93.4% and 97.2%, respectively, leaving around 104 mg-COD L(-1), 9.4 mg-NH(3)-N L(-1) and 2.6+/-0.8 mg-amoxicillin L(-1) in the final clarifier effluent. The performance evaluation of the wastewater treatment plant (WWTP) by mathematical statistic methods shown that at most of time effluent can meet the higher treatment discharge standard. In addition, the fate of amoxicillin in the full-scale WWTP and the amoxicillin removal rate of each different removal routes in UASB, NHAR, CASS, BCOT and final clarifier processes are investigated in this paper. The results show that biodegradation, adsorption and hydrolysis are the major mechanisms for amoxicillin removal. PMID- 21974849 TI - Re: Chowdhury et al. 2011. J. Hazard. Mater. Disinfection byproducts in Canadian provinces: associated cancer risks and associated medical expenses. 187: 574-584. PMID- 21974850 TI - Preparation and characterization of immobilized [A336][MTBA] in PVA-alginate gel beads as novel solid-phase extractants for an efficient recovery of Hg (II) from aqueous solutions. AB - The coarse PVA-alginate matrix gel beads entrapping the micro-droplets of the ionic liquid tricaprylylmethylammonium 2-(methylthio) benzoate ([A336][MTBA]) as novel solid-phase extractants were prepared for the removal of mercury (II) from aqueous media. The ionic liquid [A336][MTBA] immobilized PVA-alginate beads (PVA/IL) have been characterized by FTIR, SEM and TGA. The influence of the uptake conditions was investigated including aqueous pH, PVA/IL dosage, the content of [A336][MTBA] and initial Hg (II) concentration; maximum Hg (II) ion adsorption capacity obtained was 49.89 (+/- 0.11)mgg(-1) at pH 5.8 with adsorptive removal of approximately 99.98%. The selectivity of the PVA/IL beads towards Hg (II), Pb (II) and Cu (II) ions tested was Hg>Pb>Cu. The rate kinetic study was found to follow second-order and the applicability of Langmuir, Freundlich and Tempkin adsorption isotherm model were tested as well. The results of the study showed that PVA/IL beads could be efficiently used as novel extractants for the removal of divalent mercury from aqueous solutions under comparatively easy operation conditions. PMID- 21974851 TI - Characterization of the propanil biodegradation pathway in Sphingomonas sp. Y57 and cloning of the propanil hydrolase gene prpH. AB - In our previous study, the isoproturon-degrading strain Sphingomonas sp. Y57 was isolated from the wastewater treatment system of an herbicide factory. Interestingly, this strain also showed the ability to degrade propanil (3,4 dichloropropionamilide). The present work reveals that Y57 degrades propanil via the following pathway: propanil was initially hydrolyzed to 3,4-dichloroaniline (3,4-DCA) and then converted to 4,5-dichlorocatechol, which was then subjected to aromatic ring cleavage and further processing. N-acylation and N-deacylation of 3,4-DCA also occurred, and among N-acylation products, 3,4-dichloropropionanilide was found for the first time. The gene encoding the propanil hydrolase responsible for transforming propanil into 3,4-DCA was cloned from Y57 and was designated as prpH. PrpH was expressed in Escherichia coli BL21 and purified using Ni-nitrilotriacetic acid affinity chromatography. PrpH displayed the highest activity against propanil at 40 degrees C and at pH 7.0. The effect of metal ions on the propanil-degrading activity of PrpH was also determined. To our knowledge, this is the first report of a strain that can degrade both propanil and 3,4-DCA and the first identification of a gene encoding a propanil hydrolase in bacteria. PMID- 21974852 TI - An engineered cover system for mine tailings using a hardpan layer: a solidification/stabilization method for layer and field performance evaluation. AB - A cover system for mine tailings with a solidified layer (called an engineered hardpan) was developed in this study to reduce water infiltration, acid generation and sulfide oxidation. Hydrated lime and waterglass were used to produce calcium silicate, which can serve as a binder when constructing a hardpan layer. The compressive strength of each solidified/stabilized material was found to be sufficient in the lab, and the amounts of heavy metals were significantly reduced in chemical leaching tests. Various characteristics of tailings may affect the layer's mechanical strength early on, but a long curing period is capable of compensating for these effects. Heavy metals were stabilized as carbonate-bound phases and sulfide minerals were surrounded by calcium silicate matrix, thereby preventing further reaction. To evaluate the field performance of the system, a hardpan layer was installed on top of tailings on a pilot scale. Leachate with high salt content was generated in the tailings layer in the early stages of monitoring, but after approximately 6 months, the objective was achieved as the hardpan layer gradually stabilized. Notably, during the heavy rainfall season of the later monitoring stage, water infiltration was continuously prevented by the system. PMID- 21974853 TI - The future of robot-assisted laparoscopic surgery: marketing or breakthrough? For patients or for surgeons? PMID- 21974854 TI - History of robotic surgery: from AESOP(r) and ZEUS(r) to da Vinci(r). PMID- 21974855 TI - From Ambroise Pare to the surgeon of the 21(st) century, or, from surgical ligation to robots. PMID- 21974856 TI - Estimation of the prevalence of Fanconi anemia among patients with de novo acute myelogenous leukemia who have poor recovery from chemotherapy. AB - We speculated that some individuals with de novo acute myelogenous leukemia (AML) may have undiagnosed Fanconi Anemia (FA). Data from patients enrolled on AML protocol CCG-2961, published FA cohort studies, SEER, and Bayes rule were used to estimate the probability of FA among all newly diagnosed AML cases, and among those who had no or delayed recovery of the absolute neutrophil count following initial chemotherapy. We determined that the probability of undiagnosed FA in patients in a treatment trial for newly diagnosed patients was around 0.18%, and around 0.83% in the subset who had poor marrow recovery. We suggest that FA or other inherited bone marrow failure syndromes be considered prior to treatment, or certainly among those with poor recovery. PMID- 21974857 TI - Clomiphene as a novel modality for the treatment of acute myeloid leukemia: A pilot phase II study. AB - Clomiphene, an antiestrogen clinically used for ovulation induction, kills leukemic cells ex vivo via apoptosis. This study was designed to evaluate the antileukemic effect of clomiphene in patients with AML. Eleven patients with recurrent or chemoresistant AML aged 54-79 years received oral clomiphene (25 50mg per day), for seven consecutive days per cycle, up to three cycles while concurrent non intravenous chemotherapy was continued. Ten patients showed a partial response or remained stable during therapy; 7 had a rapid increase in disease parameters shortly after cessation of therapy while four patients survived 6-18 months. We believe that clomiphene contributes to stabilizing disease during therapy and appears to prolong survival in a subset of relapsed or refractory patients and may perhaps be considered as a new therapeutic option. PMID- 21974858 TI - Prevalence of efflux-mediated ciprofloxacin and levofloxacin resistance in recent clinical isolates of Pseudomonas aeruginosa and its reversal by the efflux pump inhibitors 1-(1-naphthylmethyl)-piperazine and phenylalanine-arginine-beta naphthylamide. AB - To assess the prevalence of efflux-driven fluoroquinolone (FQ) resistance in recent clinical isolates of Pseudomonas aeruginosa, a worrisome and often hospital-acquired pathogen, 115 unique strains were collected over a 5-month period, of which 27 and 33 had decreased susceptibility to ciprofloxacin (CIP) and levofloxacin (LVX), respectively. The MIC(50) (minimum inhibitory concentration for 50% of the organisms) was 16 MUg/mL for both FQs. The efflux pump inhibitors (EPIs) phenylalanine-arginine-beta-naphthylamide (PAbetaN) and 1 (1-naphthylmethyl)-piperazine (NMP) were then used to evaluate their efficacy in reducing CIP and LVX MICs. NMP did not significantly modify CIP MICs, whilst PAbetaN resulted in MIC(50) values of 2 MUg/mL and 0.125 MUg/mL for CIP and LVX, respectively. With the addition of PAbetaN, susceptibility to CIP and LVX was recovered in 6 (22.2%) and 31 (93.9%) strains, respectively. The best combination to reverse FQ resistance in this set of strains was LVX with PAbetaN. The results of this study show that the effect of an EPI is not only dependent on the species on which it is used but also on the molecule associated with it. Therefore, the design of an EPI equally efficient on all resistance-nodulation-cell division (RND) efflux pumps appears to be difficult and, from a practical point of view, if an EPI is developed for clinical use, the efficiency of its combination with a definite molecule should be assessed carefully against a wide range of clinical isolates to evaluate the real benefit of this combination. PMID- 21974859 TI - Association between IL28B polymorphisms and first-phase viral load decrease in chronic hepatitis C virus-infected patients treated with peginterferon alfa 2b/ribavirin. AB - Host polymorphisms in the IL28B region have recently been associated with outcome of treatment for hepatitis C virus (HCV) infection. This study clearly shows an association between first-phase viral load decrease and the IL28B rs12979860 polymorphism in chronic HCV-infected patients. Furthermore, a higher treatment efficiency factor (E) was found in those HCV-infected patients with a CC genotype compared with those with a CT and TT genotype. This study highlights the importance of host response mechanisms in relation to favourable clearance of HCV. PMID- 21974860 TI - Moderate exercise training and chronic caloric restriction modulate redox status in rat hippocampus. AB - Physical activity has been related to antioxidant adaptations, which is associated with health benefits, including those to the nervous system. Additionally, available data suggest exercise and a caloric restriction regimen may reduce both the incidence and severity of neurological disorders. Therefore, our aim was to compare hippocampal redox status and glial parameters among sedentary, trained, caloric-restricted sedentary and caloric-restricted trained rats. Forty male adult rats were divided into 4 groups: ad libitum-fed sedentary (AS), ad libitum-fed exercise training (AE), calorie-restricted sedentary (RS) and calorie-restricted exercise training (RE). The caloric restriction (decrease of 30% in food intake) and exercise training (moderate in a treadmill) were carried out for 3 months. Thereafter hippocampus was surgically removed, and then redox and glial parameters were assessed. Increases in reduced glutathione (GSH) levels and total antioxidant reactivity (TAR) were observed in AE, RS and RE. The nitrite/nitrate levels decreased only in RE. We found a decrease in carbonyl content in AE, RS and RE, while no modifications were detected in thiobarbituric acid reactive substances (TBARS). Total reactive antioxidant potential (TRAP), superoxide dismutase (SOD) activity, S100B and glial fibrilary acid protein (GFAP) content did not change, but caloric restriction was able to increase glutamine synthetase (GS) activity in RS and glutamate uptake in RS and RE. Exercise training, caloric restriction and both combined can decrease oxidative damage in the hippocampus, possibly involving modulation of astroglial function, and could be used as a strategy for the prevention of neurodegenerative diseases. PMID- 21974861 TI - Pattern of forebrain activation in high novelty-seeking rats following aggressive encounter. AB - We have previously demonstrated that selectively-bred High (bHR) and Low (bLR) novelty-seeking rats exhibit agonistic differences, with bHRs acting in a highly aggressive manner when facing homecage intrusion. In order to discover the specific neuronal pathways responsible for bHRs' high levels of aggression, the present study compared c-fos mRNA expression in several forebrain regions of bHR/bLR males following this experience. bHR/bLR males were housed with female rats for 2 weeks, and then the females were replaced with a male intruder for 10 min. bHR/bLR residents were subsequently sacrificed by rapid decapitation, and their brains were removed and processed for c-fos in situ hybridization. Intrusion elicited robust c-fos mRNA expression in both phenotypes throughout the forebrain, including the septum, amygdala, hippocampus, cingulate cortex, and the hypothalamus. However, bHRs and bLRs exhibited distinct activation patterns in select areas. Compared to bHR rats, bLRs expressed greater c-fos in the lateral septum and within multiple hypothalamic nuclei, while bHRs showed greater activation in the arcuate hypothalamic nucleus and in the hippocampus. No bHR/bLR differences in c-fos expression were detected in the amygdala, cortical regions, and striatum. We also found divergent 5-HT1A receptor mRNA expression within some of these same areas, with bLRs having greater 5-HT1A, but not 5-HT1B, receptor mRNA levels in the septum, hippocampus and cingulate cortex. These findings, together with our earlier work, suggest that bHRs exhibit altered serotonergic functioning within select circuits during an aggressive encounter. PMID- 21974862 TI - Gold nanoparticles induce autophagosome accumulation through size-dependent nanoparticle uptake and lysosome impairment. AB - Development of nanotechnology calls for a comprehensive understanding of the impact of nanomaterials on biological systems. Autophagy is a lysosome-based degradative pathway which plays an essential role in maintaining cellular homeostasis. Previous studies have shown that nanoparticles from various sources can induce autophagosome accumulation in treated cells. However, the underlying mechanism is still not clear. Gold nanoparticles (AuNPs) are one of the most widely used nanomaterials and have been reported to induce autophagosome accumulation. In this study, we found that AuNPs can be taken into cells through endocytosis in a size-dependent manner. The internalized AuNPs eventually accumulate in lysosomes and cause impairment of lysosome degradation capacity through alkalinization of lysosomal pH. Consistent with previous studies, we found that AuNP treatment can induce autophagosome accumulation and processing of LC3, an autophagosome marker protein. However, degradation of the autophagy substrate p62 is blocked in AuNP-treated cells, which indicates that autophagosome accumulation results from blockade of autophagy flux, rather than induction of autophagy. Our data clarify the mechanism by which AuNPs induce autophagosome accumulation and reveal the effect of AuNPs on lysosomes. This work is significant to nanoparticle research because it illustrates how nanoparticles can potentially interrupt the autophagic pathway and has important implications for biomedical applications of nanoparticles. PMID- 21974863 TI - [Cutaneous tuberculosis in an immunocompetent adult]. PMID- 21974864 TI - Melanoma cells in distinct growth phases retain specific invasive qualities during brain metastasis in vivo. PMID- 21974866 TI - Accountability and pediatric physician-researchers: are theoretical models compatible with Canadian lived experience? AB - Physician-researchers are bound by professional obligations stemming from both the role of the physician and the role of the researcher. Currently, the dominant models for understanding the relationship between physician-researchers' clinical duties and research duties fit into three categories: the similarity position, the difference position and the middle ground. The law may be said to offer a fourth "model" that is independent from these three categories.These models frame the expectations placed upon physician-researchers by colleagues, regulators, patients and research participants. This paper examines the extent to which the data from semi-structured interviews with 30 physician-researchers at three major pediatric hospitals in Canada reflect these traditional models. It seeks to determine the extent to which existing models align with the described lived experience of the pediatric physician-researchers interviewed.Ultimately, we find that although some physician-researchers make references to something like the weak version of the similarity position, the pediatric-researchers interviewed in this study did not describe their dual roles in a way that tightly mirrors any of the existing theoretical frameworks. We thus conclude that either physician researchers are in need of better training regarding the nature of the accountability relationships that flow from their dual roles or that models setting out these roles and relationships must be altered to better reflect what we can reasonably expect of physician-researchers in a real-world environment. PMID- 21974867 TI - Overlap of cognitive concepts in chronic widespread pain: an exploratory study. AB - BACKGROUND: A wide variety of cognitive concepts have been shown to play an important role in chronic widespread pain (CWP). Although these concepts are generally considered to be distinct entities, some might in fact be highly overlapping. The objectives of this study were to (i) to establish inter relationships between self-efficacy, cognitive coping styles, fear-avoidance cognitions and illness beliefs in patients with CWP and (ii) to explore the possibility of a reduction of these cognitions into a more limited number of domains. METHODS: Baseline measurement data of a prospective cohort study of 138 patients with CWP were used. Factor analysis was used to study the associations between 16 different cognitive concepts. RESULTS: Factor analysis resulted in three factors: 1) negative emotional cognitions, 2) active cognitive coping, and 3) control beliefs and expectations of chronicity. CONCLUSION: Negative emotional cognitions, active cognitive coping, control beliefs and expectations of chronicity seem to constitute principal domains of cognitive processes in CWP. These findings contribute to the understanding of overlap and uniqueness of cognitive concepts in chronic widespread pain. PMID- 21974868 TI - Optimal public rationing and price response. AB - We study optimal public health care rationing and private sector price responses. Consumers differ in their wealth and illness severity (defined as treatment cost). Due to a limited budget, some consumers must be rationed. Rationed consumers may purchase from a monopolistic private market. We consider two information regimes. In the first, the public supplier rations consumers according to their wealth information (means testing). In equilibrium, the public supplier must ration both rich and poor consumers. Rationing some poor consumers implements price reduction in the private market. In the second information regime, the public supplier rations consumers according to consumers' wealth and cost information. In equilibrium, consumers are allocated the good if and only if their costs are below a threshold (cost effectiveness). Rationing based on cost results in higher equilibrium consumer surplus than rationing based on wealth. PMID- 21974869 TI - Yes, they can! Appropriate weighting of small probabilities as a function of information acquisition. AB - So far, decision makers have mostly been shown to treat small probabilities inappropriately in risky choice. For example, one of the cornerstone assumptions of Cumulative Prospect Theory is that small probabilities are overweighted and this has been repeatedly confirmed in decisions from descriptions. Recent findings in experience-based decision making, in contrast, show that active sequential sampling of outcomes can lead decision makers to make choices which imply underweighting of small probabilities. In light of these findings, we ask whether decision makers really are unable to treat rare events appropriately. In line with theoretical approaches assuming cognitive processes of sampling and accumulation, we conjectured that decision makers display appropriate probability weighting when given the chance to draw large representative samples in little time. Two experiments comprising an "open sampling" condition corroborated this conjecture, revealing that decision makers will neither over- nor underweight small probabilities when they can rely on fast information sampling processes. PMID- 21974870 TI - Perceptual ratings of opposite spatial properties: do they lie on the same dimension? AB - The issue of unidimensionality is dealt with in various research areas in the field of Psychology (e.g. conceptual spaces, semantic modeling, psychometrics) and always involves spatial modeling. An investigation of the dimensionality of opposite spatial scales (even basic) has however not yet been carried out. In this paper we look at whether opposite judgments of height, size, width and length (high/low, large/small, wide/narrow, and long/short) imply underlying unidimensional continua. In three experiments, independent ratings for the 8 above mentioned properties were elicited with participants looking at photographic representations of various objects (Study 1), real life objects (Study 2) and spatial extensions in object-independent conditions (Study 3). Explorative and confirmative factor analysis and Andrich Extended Rating Scale Models were applied in order to determine whether the ratings referred to opposite scales on the same linear continuum. Results from the three studies consistently revealed that this is not the case. A joint analysis of the data showed interesting interactions between the spatial properties analyzed suggesting a possible explanation for the lack of unidimensionality. PMID- 21974871 TI - Relative salience affects the process of detecting changes in orientation and luminance. AB - This study tests the effect of relative saliency on perceptual comparison and decision processes in the context of change detection in which distinct visual mechanisms process two features (e.g., luminance and orientation). Townsend and Nozawa's (1995) systems factorial technology was used to investigate the process architecture and stopping rule when deciding whether luminance or orientation of a Gabor patch had changed. Experiment 1 found individual differences in decision strategies when we did not control relative saliency. One group of participants adopted co-active processing, and the other group adopted serial self-terminating processing to detect the change signals. When Experiment 2 eliminated the relative saliency, all but one observer adopted parallel processing and followed a self-terminating rule. These results support the relative saliency hypothesis and highlight the fact that observers adopt different change-detection strategies for two features, especially when relative saliency exists between the two feature dimensions. PMID- 21974872 TI - Bacterial, viral and turbidity removal by intermittent slow sand filtration for household use in developing countries: experimental investigation and modeling. AB - A two-factor three-block experimental design was developed to permit rigorous evaluation and modeling of the main effects and interactions of sand size (d(10) of 0.17 and 0.52 mm) and hydraulic head (10, 20, and 30 cm) on removal of fecal coliform (FC) bacteria, MS2 bacteriophage virus, and turbidity, under two batch operating modes ('long' and 'short') in intermittent slow sand filters (ISSFs). Long operation involved an overnight pause time between feeding of two successive 20 L batches (16 h average batch residence time (RT)). Short operation involved no pause between two 20 L batch feeds (5h average batch RT). Conditions tested were representative of those encountered in developing country field settings. Over a ten week period, the 18 experimental filters were fed river water augmented with wastewater (influent turbidity of 5.4-58.6 NTU) and maintained with the wet harrowing method. Linear mixed modeling allowed systematic estimates of the independent marginal effects of each independent variable on each performance outcome of interest while controlling for the effects of variations in a batch's actual residence time, days since maintenance, and influent turbidity. This is the first study in which simultaneous measurement of bacteria, viruses and turbidity removal at the batch level over an extended duration has been undertaken with a large number of replicate units to permit rigorous modeling of ISSF performance variability within and across a range of likely filter design configurations and operating conditions. On average, the experimental filters removed 1.40 log fecal coliform CFU (SD 0.40 log, N=249), 0.54 log MS2 PFU (SD 0.42 log, N=245) and 89.0 percent turbidity (SD 6.9 percent, N=263). Effluent turbidity averaged 1.24 NTU (SD 0.53 NTU, N=263) and always remained below 3 NTU. Under the best performing design configuration and operating mode (fine sand, 10 cm head, long operation, initial HLR of 0.01-0.03 m/h), mean 1.82 log removal of bacteria (98.5%) and mean 0.94 log removal of MS2 viruses (88.5%) were achieved. Results point to new recommendations regarding filter design, manufacture, and operation for implementing ISSFs in local settings in developing countries. Sand size emerged as a critical design factor on performance. A single layer of river sand used in this investigation demonstrated removals comparable to those reported for 2 layers of crushed sand. Pause time and increased residence time each emerged as highly beneficial for improving removal performance on all four outcomes. A relatively large and significant negative effect of influent turbidity on MS2 viral removal in the ISSF was measured in parallel with a much smaller weaker positive effect of influent turbidity on FC bacterial removal. Disturbance of the schmutzdecke by wet harrowing showed no effect on virus removal and a modest reductive effect on the bacterial and turbidity removal as measured 7 days or more after the disturbance. For existing coarse sand ISSFs, this research indicates that a reduction in batch feed volume, effectively reducing the operating head and increasing the pore:batch volume ratio, could improve their removal performance by increasing batch residence time. PMID- 21974873 TI - Xenobiotic removal efficiencies in wastewater treatment plants: residence time distributions as a guiding principle for sampling strategies. AB - The effect of mixing regimes and residence time distribution (RTD) on solute transport in wastewater treatment plants (WWTPs) is well understood in environmental engineering. Nevertheless, it is frequently neglected in sampling design and data analysis for the investigation of polar xenobiotic removal efficiencies in WWTPs. Most studies on the latter use 24-h composite samples in influent and effluent. The effluent sampling period is often shifted by the mean hydraulic retention time assuming that this allows a total coverage of the influent load. However, this assumption disregards mixing regime characteristics as well as flow and concentration variability in evaluating xenobiotic removal performances and may consequently lead to biased estimates or even negative elimination efficiencies. The present study aims at developing a modeling approach to estimate xenobiotic removal efficiencies from monitoring data taking the hydraulic RTD in WWTPs into consideration. For this purpose, completely mixed tanks-in-series were applied to address hydraulic mixing regimes in a Luxembourg WWTP. Hydraulic calibration for this WWTP was performed using wastewater conductivity as a tracer. The RTD mixing approach was coupled with first-order biodegradation kinetics for xenobiotics covering three classes of biodegradability during aerobic treatment. Model simulations showed that a daily influent load is distributed over more than one day in the effluent. A 24-h sampling period with an optimal time offset between influent and effluent covers less than the half of the influent load in a dry weather scenario. According to RTD calculations, an optimized sampling strategy covering four consecutive measuring days in the influent would be necessary to estimate the full-scale elimination efficiencies with sufficient accuracy. Daily variations of influent flow and concentrations can substantially affect the reliability of these sampling results. Commonly reported negative removal efficiencies for xenobiotics might therefore be a consequence of biased sampling schemes. In this regard, the present study aims at contributing to bridge the gap between environmental chemistry and engineering practices. PMID- 21974874 TI - Size and structure evolution of kaolin-Al(OH)3 flocs in the electroflocculation process: a study using static light scattering. AB - Electroflocculation (EF) is gaining recognition as an alternative process to conventional coagulation/flocculation. The electrical current applied in EF that generates the active coagulant species creates a unique chemical/physical environment in which competing redox reactions occur, primarily water electrolysis. This causes a transient rise in pH, due to cathodic formation of hydroxyl ions, which, in turn, causes a continuous shift in coagulation/flocculation mechanisms throughout the process. This highly impacts the formation of a sweep floc regime that relies on precipitation of metal hydroxide and its growth into floc. The size and structural evolution of kaolin Al(OH)(3) flocs was examined using static light scattering techniques, in aim of elucidating kinetic aspects of the process. An EF cell was operated in batch mode and comprised of two concentric electrodes - a stainless steel cathode (inner electrode) and an aluminum anode (outer electrode). The cell was run at constant current between 0.042A and 0.22A, and analyses performed at pre-determined time intervals. The results demonstrate that EF is able to generate a range of flocs, exhibiting different growth rates and structural characteristics, depending on the conditions of operation. Growth patterns were sigmoidal and a linear correlation between growth rate and current applied was observed. The dependency of growth rate on current can be related to initial pH and aluminum dosing, with a stronger dependency apparent for initial optimal sweep floc regime. All flocs exhibited a fragile nature and undergo compaction and structural fluctuations during growth. This is the first time size and structural evolution of flocs formed in the EF process is reported. PMID- 21974875 TI - Enantiospecific fate of ibuprofen, ketoprofen and naproxen in a laboratory-scale membrane bioreactor. AB - The enantiospecific fate of three common pharmaceuticals was monitored in a laboratory-scale membrane bioreactor (MBR). The MBR was operated with a hydraulic retention time of 24 h and a mixed liquor suspended solids concentration of 8.6 10 g/L. Standard solutions of ibuprofen, ketoprofen and naproxen were dosed into the synthetic feed of the MBR. Influent and permeate samples were then collected for enantiospecific analysis. The individual (R)- and (S)-enantiomers of the three pharmaceuticals were derivatised using a chiral derivatizing agent to form pairs of diastereomers, which could then be separated and analysed by gas chromatography-tandem mass spectrometry (GC-MS/MS). Accurate quantitation of individual enantiomers was undertaken by an isotope dilution process. By comparing the total concentration (as the sum of the two enantiomers) in the MBR influent and permeate, ibuprofen, ketoprofen and naproxen concentrations were observed to have been reduced as much as 99%, 43% and 68%, respectively. Furthermore, evidence of enantioselective biodegradation was observed for all three pharmaceuticals. (S)-Ibuprofen was shown to be preferentially degraded compared to (R)-ibuprofen with an average decrease in enantiomeric fraction (EF) from 0.52 to 0.39. In contrast, (R)-ketoprofen was preferentially degraded compared to (S)-ketoprofen with a relatively minor increase in EF from 0.52 to 0.63. The use of a relatively pure enantiomeric solution of (S)-naproxen resulted in a significant change in EF from 0.99 to 0.65. However, this experiment consistently revealed significantly increased concentrations of (R)-naproxen during MBR treatment. It is hypothesised that the source of this (R)-naproxen was the enantiomeric inversion of (S)-naproxen. Such enantiomeric inversion of chiral pharmaceuticals during wastewater treatment processes has not previously been reported. PMID- 21974876 TI - Gender and social environment modulate the effects of testosterone on social behavior: comment on Eisenegger et al. PMID- 21974878 TI - Continuous acetone-butanol-ethanol fermentation using SO2-ethanol-water spent liquor from spruce. AB - SO2-ethanol-water (SEW) spent liquor from spruce chips was successfully used for batch and continuous production of acetone, butanol and ethanol (ABE). Initially, batch experiments were performed using spent liquor to check the suitability for production of ABE. Maximum concentration of total ABE was found to be 8.79 g/l using 4-fold diluted SEW liquor supplemented with 35 g/l of glucose. The effect of dilution rate on solvent production, productivity and yield was studied in column reactor consisting of immobilized Clostridium acetobutylicum DSM 792 on wood pulp. Total solvent concentration of 12 g/l was obtained at a dilution rate of 0.21 h(-1). The maximum solvent productivity (4.86 g/l h) with yield of 0.27 g/g was obtained at dilution rate of 0.64 h(-1). Further, to increase the solvent yield, the unutilized sugars were subjected to batch fermentation. PMID- 21974877 TI - Oxidative damages in tubular epithelial cells in IgA nephropathy: role of crosstalk between angiotensin II and aldosterone. AB - BACKGROUND: Inhibition of the renin-angiotensin-aldosterone system (RAAS) slows down the progression of chronic renal diseases (CKD) including IgA nephropathy (IgAN). Herein, we studied the pathogenetic roles of aldosterone (Aldo) in IgAN. METHODS: Human mesangial cells (HMC) was activated with polymeric IgA (pIgA) from IgAN patients and the effects on the expression of RAAS components and TGF-beta synthesis examined. To study the roles of RAAS in the glomerulotubular communication, proximal tubular epithelial cells (PTEC) was cultured with conditioned medium from pIgA-activated HMC with eplerenone or PD123319, the associated apoptotic event was measured by the generation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and reactive oxygen species (ROS). RESULTS: Polymeric IgA up-regulated the Aldo synthesis and aldosterone synthase expression by HMC. The release of TGF-beta by HMC was up-regulated synergistically by AngII and Aldo and this was inhibited by incubation of HMC with losartan plus eplerenone. Cultured PTEC express the mineralocorticoid receptor, but not synthesizing aldosterone. Apoptosis, demonstrated by cleaved PARP expression and caspase 3 activity, was induced in PTEC activated by conditioned medium prepared from HMC cultured with pIgA from IgAN patients. This apoptotic event was associated with increased generation of NADPH oxidase and ROS. Pre-incubation of PTEC with PD123319 and eplerenone achieved complete inhibition of PTEC apoptosis. CONCLUSIONS: Our data suggest that AngII and Aldo, released by pIgA activated HMC, served as mediators for inducing apoptosis of PTEC in glomerulo-tubular communications. Crosstalk between AngII and Aldo could participate in determining the tubular pathology of IgAN. PMID- 21974879 TI - Enzymatic synthesis of fructooligosaccharides with high 1-kestose concentrations using response surface methodology. AB - Response surface methodology was used as an optimization tool for the production of short chain fructooligosaccharides (sc-FOS) using the commercial cellulolytic enzyme preparation, Rohapect CM. Three independent variables, temperature, concentrations of sucrose and enzyme were tested in the reaction medium. The responses of the design were, yield (gsc-FOS/100 g initial sucrose), 1-kestose (g/100 g sc-FOS) and volumetric productivity (gsc-FOS/Lh). Significant effects on the three responses included a quadratic effect (temperature), a linear effect (sucrose and enzyme concentrations) and an interaction between temperature and sucrose concentration. The cost-effective conditions to support the process in a high competitive market were 50 degrees C, 6.6 TU/mL enzyme, 2.103 M sucrose in 50 mM acetate buffer at pH 5.5, and the synthesis for a 5 h reaction time. Under these conditions, a high YP/S (63.8%), QP (91.9 g/Lh) and sGF2 (68.2%) was achieved. PMID- 21974880 TI - Preparation and characterization of cross-linked enzyme aggregates (CLEAs) of recombinant poly-3-hydroxybutyrate depolymerase from Streptomyces exfoliatus. AB - Cross-linked enzyme aggregates of poly-3-hydroxybutyrate (PHB) depolymerase from Streptomyces exfoliatus (PhaZ(Sex)-CLEAs) have been prepared. Acetone was used as the precipitating agent, while addition of bovine serum albumin (BSA) facilitated CLEAs formation. Conditions for enzyme precipitation and cross-linking have been optimized, and confocal scanning microscopy showed a homogeneous enzyme distribution in the biocatalyst. Obtained PhaZ(Sex)-CLEAs presented an average size of 50-300 MUm, showing a high PHB depolymerase activity of 255 U/g wet biocatalyst at 40 degrees C and pH 7.0. Temperature-activity profile of PhaZ(Sex) CLEAs at pH 8.0 showed that the highest activity for pNPB hydrolysis was achieved at 60 degrees C, whereas pH-activity profile at 40 degrees C indicated that highest activity for PHB hydrolysis was achieved at pH 7.0. Additionally, immobilized biocatalyst could be recycled at least for 20 consecutive batch reactions without loss of catalytic activity, and showed higher pH and temperature stability, and better tolerance to several organic solvents than its soluble counterpart. PMID- 21974881 TI - Enhancement of hydrogen production in a single chamber microbial electrolysis cell through anode arrangement optimization. AB - Reducing the inner resistances is crucial for the enhancement of hydrogen generation in microbial electrolysis cells (MECs). This study demonstrates that the optimization of the anode arrangement is an effective strategy to reduce the system resistances. By changing the normal MEC configuration into a stacking mode, namely separately placing the contacted anodes from one side to both sides of cathode in parallel, the solution, biofilm and polarization resistances of MECs were greatly reduced, which was also confirmed with electrochemical impedance spectroscopy analysis. After the anode arrangement optimization, the current and hydrogen production rate (HPR) of MEC could be enhanced by 72% and 118%, reaching 621.3+/-20.6 A/m3 and 5.56 m3/m3 d respectively, under 0.8 V applied voltage. A maximum current density of 1355 A/m3 with a HPR of 10.88 m3/m3 d can be achieved with 1.5 V applied voltage. PMID- 21974882 TI - Co-pyrolysis of sunflower-oil cake with potassium carbonate and zinc oxide using plasma torch to produce bio-fuels. AB - This study examined the effects of additives of potassium carbonate (K2CO3) and zinc oxide (ZnO) on the pyrolysis of waste sunflower-oil cake using a 60 kW pilot scale plasma torch reactor. The major gaseous products were CO and H2. The productions of CO and CH4 increased while that of H2 decreased with the addition of K2CO3. The use of ZnO reduced while enhanced the formation of CO and H2, respectively. In order to match the appeal of resource reutilization, one can use the waste K2CO3 resulted from the sorption of CO2 with KOH in greenhouse gas control and the waste ZnO obtained from the melting process as additives for the co-pyrolysis of sunflower-oil cake, yielding fuels rich in CO and H2, respectively. PMID- 21974883 TI - Activity and stability of immobilized carbonic anhydrase for promoting CO2 absorption into a carbonate solution for post-combustion CO2 capture. AB - An Integrated Vacuum Carbonate Absorption Process (IVCAP) currently under development could significantly reduce the energy consumed when capturing CO2 from the flue gases of coal-fired power plants. The biocatalyst carbonic anhydrase (CA) has been found to effectively promote the absorption of CO2 into the potassium carbonate solution that would be used in the IVCAP. Two CA enzymes were immobilized onto three selected support materials having different pore structures. The thermal stability of the immobilized CA enzymes was significantly greater than their free counterparts. For example, the immobilized enzymes retained at least 60% of their initial activities after 90 days at 50 degrees C compared to about 30% for their free counterparts under the same conditions. The immobilized CA also had significantly improved resistance to concentrations of sulfate (0.4 M), nitrate (0.05 M) and chloride (0.3 M) typically found in flue gas scrubbing liquids than their free counterparts. PMID- 21974884 TI - Logistics system design for biomass-to-bioenergy industry with multiple types of feedstocks. AB - It is technologically possible for a biorefinery to use a variety of biomass as feedstock including native perennial grasses (e.g., switchgrass) and agricultural residues (e.g., corn stalk and wheat straw). Incorporating the distinct characteristics of various types of biomass feedstocks and taking into account their interaction in supplying the bioenergy production, this paper proposed a multi-commodity network flow model to design the logistics system for a multiple feedstock biomass-to-bioenergy industry. The model was formulated as a mixed integer linear programming, determining the locations of warehouses, the size of harvesting team, the types and amounts of biomass harvested/purchased, stored, and processed in each month, the transportation of biomass in the system, and so on. This paper demonstrated the advantages of using multiple types of biomass feedstocks by comparing with the case of using a single feedstock (switchgrass) and analyzed the relationship of the supply capacity of biomass feedstocks to the output and cost of biofuel. PMID- 21974885 TI - Significant factors selection in the chemical and enzymatic hydrolysis of lignocellulosic residues by a genetic algorithm analysis and comparison with the standard Plackett-Burman methodology. AB - A comparison between the classic Plackett-Burman design (PB) ANOVA analysis and a genetic algorithm (GA) approach to identify significant factors have been carried out. This comparison was made by applying both analyses to data obtained from the experimental results when optimizing both chemical and enzymatic hydrolysis of three lignocellulosic feedstocks (corn and wheat bran, and pine sawdust) by a PB experimental design. Depending on the kind of biomass and the hydrolysis being considered, different results were obtained. Interestingly, some interactions were found to be significant by the GA approach and allowed to identify significant factors, that otherwise, based only in the classic PB analysis, would have not been taken into account in a further optimization step. Improvements in the fitting of c.a. 80% were obtained when comparing the coefficient of determination (R2) computed for both methods. PMID- 21974886 TI - Model-based predictions of anaerobic digestion of agricultural substrates for biogas production. AB - A modified Anaerobic Digestion Model No. 1 (ADM1), calibrated on a laboratory digester with a feeding mix of 30% weight of cow manure and 70% weight of corn silage, was implemented, showing its performances of simulation as a decision making and planning-supporting tool for the anaerobic digestion of agricultural substrates. The virtual fermenter obtained was used to conduct simulations with different feeding compositions and loading rates of cow manure, corn silage, grass silage and rape oil. All simulations were started at the same initial state which was represented by a steady state with an organic loading rate of 2.5 kg ODM/(mdigester3*d). The effects of the different feeding combinations on biogas composition and biogas yield were predicted reasonably, and partly verified with the available literature data. Results demonstrated that the simulations could be helpful for taking decisions on agricultural biogas plant operation or experimental set-ups, if used advisedly. PMID- 21974887 TI - Production of fuel ethanol from bamboo by concentrated sulfuric acid hydrolysis followed by continuous ethanol fermentation. AB - An efficient process for the production of fuel ethanol from bamboo that consisted of hydrolysis with concentrated sulfuric acid, removal of color compounds, separation of acid and sugar, hydrolysis of oligosaccharides and subsequent continuous ethanol fermentation was developed. The highest sugar recovery efficiency was 81.6% when concentrated sulfuric acid hydrolysis was carried out under the optimum conditions. Continuous separation of acid from the saccharified liquid after removal of color compounds with activated carbon was conducted using an improved simulated moving bed (ISMB) system, and 98.4% of sugar and 90.5% of acid were recovered. After oligosaccharide hydrolysis and pH adjustment, the unsterilized saccharified liquid was subjected to continuous ethanol fermentation using Saccharomycescerevisiae strain KF-7. The ethanol concentration, the fermentation yield based on glucose and the ethanol productivity were approximately 27.2 g/l, 92.0% and 8.2 g/l/h, respectively. These results suggest that the process is effective for production of fuel ethanol from bamboo. PMID- 21974888 TI - Efficient bioconversion of compactin to pravastatin by the quinoline-degrading microorganism Pseudonocardia carboxydivorans isolated from petroleum-contaminated soil. AB - Pravastatin is one of the first available statins on the market. The purpose of this study was to isolate and identify the quinoline-degrading microorganism from petroleum-contaminated soil that could bioconvert compactin to pravastatin. There were 10,011 microorganism colonies isolated; five strains showed a higher capability for quinoline biodegradation. These five strains were evaluated for their pravastatin bioconversion ability; Pseudonocardia sp. had the highest efficiency for conversion of compactin to pravastatin. The strain was further identified as Pseudonocardia carboxydivorans PAH4. The bioconversion rates were studied under difference incubation conditions. Pre-incubation in medium containing 0.005% compactin sodium, resulted in the compactin utilization rate of almost 100% in a 1mg/ml compactin-containing medium. The rate of conversion of pravastatin was up to 68% after 6 days of incubation. In conclusion, the results of this study suggest that P. carboxydivorans PAH4 could be considered a candidate for the production of pravastatin on an industrial scale. PMID- 21974889 TI - Study of a combined sulfur autotrophic with proton-exchange membrane electrodialytic denitrification technology: sulfate control and pH balance. AB - A novel combined system established for nitrate removal from aqueous solution consisted of two parts: sulfur autotrophic denitrification and bio electrochemical denitrification based on proton-exchange membrane electrodialysis (PEMED). The system was operated at various hydraulic retention times (HRT) and current intensities. Its optimum operation condition was also determined. The combined process had pH adjustment thus generating less nitrite than PEMED process. The denitrification rate of sulfur autotrophic part was dependent on HRT, while shorter HRT could reduce the sulfate generated by the sulfur autotrophic process. The denitrification rate of PEMED process depended on the applied current. For 32+/-1 mg-N/L nitrate in influent, the optimum operation parameters of combined process were: HRT 2h; applied current 350 mA. The combined reactor could achieve 95.8% nitrate removal without nitrite accumulation, the pH of effluent kept neutral and the sulfate of effluent was 202.1 mg/L, lower than the drinking water standard in China. PMID- 21974890 TI - A comparative analysis of dietary intakes during pregnancy in Europe: a planned pooled analysis of birth cohort studies. AB - BACKGROUND: There is growing evidence that despite the absence of marked deficiencies, diet during pregnancy has important implications for maternal and child health in industrialized countries. At present, relatively little is known about prevailing patterns of intake across groups with diverse sociodemographic and lifestyle patterns in these settings. OBJECTIVES: The aims of this study were to develop methods for the standardization of food group intake data and to describe the process of applying these methods to existing pregnancy cohort studies, which included >200,000 women across Europe. DESIGN: The study developed a detailed standardization protocol to harmonize intakes of selected food groups, which included fruit, vegetables, meats, seafood, and dairy products. Standardization is necessary to facilitate valid comparisons of intake patterns and disparities across countries and will lead to the development of harmonized databases for possible future pooled analyses. RESULTS: On the basis of comparisons with previously coordinated multicountry studies, preliminary data suggest that the standardization process yielded sufficiently comparable intake data, which indicate differences in food cultures across the countries that participated. CONCLUSIONS: This project provides lessons on the feasibility of harmonizing dietary intake data from existing studies, which can be applied in future post hoc standardization efforts. The data yielded in this analysis will also provide useful information for the development of food and nutrition policies for pregnant women in Europe, including the identification of population subgroups in which dietary inadequacies during pregnancy may be widespread. PMID- 21974891 TI - The Early Nutrition Programming Project (EARNEST): 5 y of successful multidisciplinary collaborative research. AB - Differences in nutritional experiences during sensitive periods in early life, both before and after birth, can program a person's future development, metabolism, and health. A better scientific understanding of early nutrition programming holds enormous potential for implementing preventive strategies to enhance individuals' long-term health, well-being, and performance. This understanding could reduce costs of health care and social services and may enhance the wealth of societies. The Early Nutrition Programming Project (EARNEST) brought together a multidisciplinary team of international scientists and leaders in key areas of the early nutrition programming field from 40 major research centers across 16 European countries. The project had a total budget of 16.5 million Euros and was funded by the European Communities under the Sixth Framework Program for Research and Technical Development and coordinated by the Children's Hospital at Ludwig-Maximilians-University of Munich. The integrated program of work combined experimental studies in humans, prospective observational studies, and mechanistic animal work, including physiologic studies, cell culture models, and molecular biology techniques. The project lasted from April 2005 to October 2010. After the end of the project, the Early Nutrition Academy (http://www.early-nutrition.org) continues to serve as a platform for the exchange of information, scientific collaboration, and training activities in the area of programming. This article highlights some of the scientific results, achievements, and efforts of EARNEST. PMID- 21974892 TI - Health economic potential of early nutrition programming: a model calculation of long-term reduction in blood pressure and related morbidity costs by use of long chain polyunsaturated fatty acid-supplemented formula. AB - BACKGROUND: The reported effect sizes of early nutrition programming on long-term health outcomes are often small, and it has been questioned whether early interventions would be worthwhile in enhancing public health. OBJECTIVE: We explored the possible health economic consequences of early nutrition programming by performing a model calculation, based on the only published study currently available for analysis, to evaluate the effects of supplementing infant formula with long-chain polyunsaturated fatty acids (LC-PUFAs) on lowering blood pressure and lowering the risk of hypertension-related diseases in later life. DESIGN: The costs and health effects of LC-PUFA-enriched and standard infant formulas were compared by using a Markov model, including all relevant direct and indirect costs based on German statistics. We assessed the effect size of blood pressure reduction from LC-PUFA-supplemented formula, the long-term persistence of the effect, and the effect of lowered blood pressure on hypertension-related morbidity. RESULTS: The cost-effectiveness analysis showed an increased life expectancy of 1.2 quality-adjusted life-years and an incremental cost effectiveness ratio of -630 Euros (discounted to present value) for the LC-PUFA formula in comparison with standard formula. LC-PUFA nutrition was the superior strategy even when the blood pressure-lowering effect was reduced to the lower 95% CI. CONCLUSIONS: Breastfeeding is the recommended feeding practice, but infants who are not breastfed should receive an appropriate infant formula. Following this model calculation, LC-PUFA supplementation of infant formula represents an economically worthwhile prevention strategy, based on the costs derived from hypertension-linked diseases in later life. However, because our analysis was based on a single randomized controlled trial, further studies are required to verify the validity of this thesis. PMID- 21974893 TI - Reproducibility and day time bias correction of optoelectronic leg volumetry: a prospective cohort study. AB - BACKGROUND: Leg edema is a common manifestation of various underlying pathologies. Reliable measurement tools are required to quantify edema and monitor therapeutic interventions. Aim of the present work was to investigate the reproducibility of optoelectronic leg volumetry over 3 weeks' time period and to eliminate daytime related within-individual variability. METHODS: Optoelectronic leg volumetry was performed in 63 hairdressers (mean age 45 +/- 16 years, 85.7% female) in standing position twice within a minute for each leg and repeated after 3 weeks. Both lower leg (legBD) and whole limb (limbBF) volumetry were analysed. Reproducibility was expressed as analytical and within-individual coefficients of variance (CVA, CVW), and as intra-class correlation coefficients (ICC). RESULTS: A total of 492 leg volume measurements were analysed. Both legBD and limbBF volumetry were highly reproducible with CVA of 0.5% and 0.7%, respectively. Within-individual reproducibility of legBD and limbBF volumetry over a three weeks' period was high (CVW 1.3% for both; ICC 0.99 for both). At both visits, the second measurement revealed a significantly higher volume compared to the first measurement with a mean increase of 7.3 ml +/- 14.1 (0.33% +/- 0.58%) for legBD and 30.1 ml +/- 48.5 ml (0.52% +/- 0.79%) for limbBF volume. A significant linear correlation between absolute and relative leg volume differences and the difference of exact day time of measurement between the two study visits was found (P < .001). A therefore determined time-correction formula permitted further improvement of CVW. CONCLUSIONS: Leg volume changes can be reliably assessed by optoelectronic leg volumetry at a single time point and over a 3 weeks' time period. However, volumetry results are biased by orthostatic and daytime-related volume changes. The bias for day-time related volume changes can be minimized by a time-correction formula. PMID- 21974894 TI - Characterization of enhanced-fluidity liquid hydrophilic interaction chromatography for the separation of nucleosides and nucleotides. AB - Hydrophilic interaction chromatography (HILIC) is a liquid chromatographic separation mechanism commonly used for polar biological molecules. The use of enhanced-fluidity liquid chromatography (EFLC) with mixtures of methanol/water/carbon dioxide is compared to acetonitrile/water mobile phases for the separation of nucleosides and nucleotides under HILIC conditions. Enhanced fluidity liquid chromatography involves using common mobile phases with the addition of substantial proportions of a dissolved gas which provides greater mobile phase diffusivity and lower viscosity. The impact of varying several experimental parameters, including temperature, addition of base, salt, and CO2 was studied to provide optimized HILIC separations. Each of these parameters plays a key role in the retention of the analytes, which demonstrates the complexity of the retention mechanism in HILIC. The tailing of phosphorylated compounds was overcome with the use of phosphate salts and the addition of a strong base; efficiency and peak asymmetry were compared with the addition of either triethylamine (TEA), 1,4-diazabicyclo [2.2.2] octane (DABCO) or 1,5 diazabicyclo [4.3.0] non-5-ene (DBN). DBN and DABCO both led to increased efficiency and lower peak asymmetry; DBN provided the best results. Sodium chloride and carbon dioxide were added to enhance the selectivity between the analytes, giving a successful isocratic separation of nucleosides and nucleotides within 8 min. The retention mechanism involved in EFL-HILIC was explored by varying the temperature and the mole fraction of CO2. These studies showed that partitioning was the dominant mechanism. The thermodynamics study confirmed that the solvent strength is maintained in EFLC and that a change in entropy was mainly responsible for the improved selectivity. The selectivity using methanol/water/carbon dioxide varied greatly compared to that obtained with acetonitrile/water. Finally while this study highlights the optimization of EFL HILIC for the separation of nucleosides and nucleotides under isocratic conditions, this is also an example of the broad range of polarities of compounds that EFL-HILIC can separate. PMID- 21974895 TI - Headspace needle-trap analysis of priority volatile organic compounds from aqueous samples: application to the analysis of natural and waste waters. AB - Combining headspace (HS) sampling with a needle-trap device (NTD) to determine priority volatile organic compounds (VOCs) in water samples results in improved sensitivity and efficiency when compared to conventional static HS sampling. A 22 gauge stainless steel, 51-mm needle packed with Tenax TA and Carboxen 1000 particles is used as the NTD. Three different HS-NTD sampling methodologies are evaluated and all give limits of detection for the target VOCs in the ng L-1 range. Active (purge-and-trap) HS-NTD sampling is found to give the best sensitivity but requires exhaustive control of the sampling conditions. The use of the NTD to collect the headspace gas sample results in a combined adsorption/desorption mechanism. The testing of different temperatures for the HS thermostating reveals a greater desorption effect when the sample is allowed to diffuse, whether passively or actively, through the sorbent particles. The limits of detection obtained in the simplest sampling methodology, static HS-NTD (5 mL aqueous sample in 20 mL HS vials, thermostating at 50 degrees C for 30 min with agitation), are sufficiently low as to permit its application to the analysis of 18 priority VOCs in natural and waste waters. In all cases compounds were detected below regulated levels. PMID- 21974896 TI - Lymph vessel density in seminomatous testicular cancer assessed with the specific lymphatic endothelium cell markers D2-40 and LYVE-1: correlation with pathologic parameters and clinical outcome. AB - OBJECTIVES: To evaluate the role of lymph vessel density (LVD) and lymphangiogenesis in seminomatous testicular cancer (STC) by using the lymphatic endothelial cell (LEC) markers LYVE-1 and D2-40. METHODS AND MATERIALS: Paraffin embedded tumor specimens from 40 patients with STC were stained by specific D2-40 and Lyve-1 antibodies. LVD was measured in different representative and standardized areas. Fluorescence double immunostaining for Lyve-1 and Ki-67 was performed and results were correlated with clinicopathologic data. The median follow-up period was 55 (range 10-135) months. RESULTS: Mean intratumoral LVD (D2 40: 1.30 +/- 1.99; Lyve-1: 1.82 +/- 2.34) was significantly lower than peritumoral LVD (D2-40: 4.94 +/- 2.58; Lyve-1: 4.62 +/- 2.73) and LVD in nontumoral areas (D2-40: 4.81 +/- 3.79; Lyve-1: 4.22 +/- 3.19). There was no significant difference between LVD measures when using D2-40 or LYVE-1. Detection rates of lymphatic vascular invasion (LVI) were significantly higher than in conventional HE-stained sections (77.5% vs. 52.5%). No proliferating lymphatic vessels were found. CONCLUSIONS: We found that LVD is decreased within tumor areas of STC. Despite a higher peritumoral LVD, no signs of proliferating endothelial cells were observed, suggesting a lack of lymphangiogenesis in STC. Detection of LVI can be optimized by specific D2-40 or LYVE-1 staining. PMID- 21974897 TI - The calls on the government from the Cancer Research UK. PMID- 21974898 TI - Er,CR:YSGG lasers induce fewer dysplastic-like epithelial artefacts than CO2 lasers: an in vivo experimental study on oral mucosa. AB - Our aim was to assess wounds made by lasers (CO(2) and Er,Cr:YSGG) for their epithelial architectural changes and width of damage. We allocated 60 Sprague Dawley((r)) rats into groups: glossectomy by CO(2) laser at 3 different wattages (n=10 in each); glossectomy by Er,Cr:YSGG laser at two different emissions (n=10 in each), and a control group (n=10). Histological examination assessed both prevalence and site of thermal artefacts for each group. Both lasers (CO(2) and Er,Cr:YSGG) caused the same type of cytological artefacts. The 3W Er,Cr:YSGG laser produced the fewest cytological artefacts/specimen, and was significantly different from the other experimental groups: 3W CO(2) laser (95% CI=0.8 to 1.0); the 6W CO(2) laser (95% CI=0.1 to 2.0) and the 10W CO(2) laser (95% CI=1.1 to 3.0). CO(2) lasers (3-10W) generate epithelial damage that can simulate dysplastic changes with cytological atypia that affects mainly the basal and suprabasal layers. Irradiation with Er,CR:YSGG laser (2-4W) produces significantly fewer cellular artefacts and less epithelial damage, which may be potentially useful for biopsy of oral mucosa. PMID- 21974899 TI - Prototyped flexible grafting tray for reconstruction of mandibular defects. AB - In our previous studies, prototyped individual bone-grafting trays have been used to restore discontinuous mandibular defects. However, the attempts have shown that the trays have shielded the graft from stress, which caused considerable resorption of bone. To eliminate the shielding, we designed a flexible tray. Finite element analysis was used to compare the distribution of strain on the bone grafts that were placed in flexible and conventional trays. The analogue computation suggested that most of the strain on the graft in the flexible tray resulted in a beneficial mechanical environment, while in the conventional tray more than half of graft was in the lowest class of strain (disuse - <50 MUstrains). Animal experiments were conducted on hybrid dogs, and the prototype flexible tray was used to carry particles of autologous cancellous iliac bone to reconstruct a 40 mm defect in the mandibular body. Sequential radionuclide bone imaging was used to monitor the bone metabolism. Animals were killed at 4, 12 and 24 weeks, and specimens processed for quantitative histological examination. The data from the flexible trays were compared with those from the conventional trays, as in our previous study. The results showed that bone metabolism was more active in the flexible tray than in the conventional tray during the early stages. There was increased bony adaptation in the flexible tray. These results indicate that the flexible tray can efficiently eliminate the shielding from stress, and allow more occlusive force to be conducted on to the bone graft, which results in better remodelling of the graft. PMID- 21974900 TI - Polyglycolic acid sheets with fibrin glue (MCFP technique) for resection of oral mucosa. PMID- 21974901 TI - Bayesian probit regression model for the diagnosis of pulmonary fibrosis: proof of-principle. AB - BACKGROUND: The accurate diagnosis of idiopathic pulmonary fibrosis (IPF) is a major clinical challenge. We developed a model to diagnose IPF by applying Bayesian probit regression (BPR) modelling to gene expression profiles of whole lung tissue. METHODS: Whole lung tissue was obtained from patients with idiopathic pulmonary fibrosis (IPF) undergoing surgical lung biopsy or lung transplantation. Controls were obtained from normal organ donors. We performed cluster analyses to explore differences in our dataset. No significant difference was found between samples obtained from different lobes of the same patient. A significant difference was found between samples obtained at biopsy versus explant. Following preliminary analysis of the complete dataset, we selected three subsets for the development of diagnostic gene signatures: the first signature was developed from all IPF samples (as compared to controls); the second signature was developed from the subset of IPF samples obtained at biopsy; the third signature was developed from IPF explants. To assess the validity of each signature, we used an independent cohort of IPF and normal samples. Each signature was used to predict phenotype (IPF versus normal) in samples from the validation cohort. We compared the models' predictions to the true phenotype of each validation sample, and then calculated sensitivity, specificity and accuracy. RESULTS: Surprisingly, we found that all three signatures were reasonably valid predictors of diagnosis, with small differences in test sensitivity, specificity and overall accuracy. CONCLUSIONS: This study represents the first use of BPR on whole lung tissue; previously, BPR was primarily used to develop predictive models for cancer. This also represents the first report of an independently validated IPF gene expression signature. In summary, BPR is a promising tool for the development of gene expression signatures from non neoplastic lung tissue. In the future, BPR might be used to develop definitive diagnostic gene signatures for IPF, prognostic gene signatures for IPF or gene signatures for other non-neoplastic lung disorders such as bronchiolitis obliterans. PMID- 21974902 TI - Histopathological liver alterations in juvenile rabbit fish (Siganus canaliculatus) exposed to light Arabian crude oil, dispersed oil and dispersant. AB - With the heavy transport of crude oil there is an increasing risk of a major oil spill in the Gulf waters; however, there have been few studies on the impact of oil spills and subsequent remedial action on Gulf fish. The aim of the experiment was to investigate the effects of acute exposure to water soluble fraction (WAF) of light Arabian crude oil, dispersed oil and dispersant on the liver of the juvenile rabbit fish (Siganus canaliculatus), observing several histopathological biomarkers of the liver at different time points and different doses. The concentrations used (3-100 percent WAF) simulated a range of possible oil pollution events. The main alterations observed in this study include hepatocyte swelling and cytoplasmic vacuolisation, megalocytosis, coagulative dispersed necrosis, lymphocytic infiltration, melanomacrophage aggregates, spongiosis hepatis, pericholangiitis, and bile stagnosis. Treated livers showed significantly higher total index values than the control group (p<0.01). According to the total liver index, liver exposed to WAF, dispersed oil or dispersant showed significant histopathologic alterations compared with the control fish (Mann-Whitney U-test; p<0.01). Components of the total liver index, (circulatory, degenerative, proliferative, and inflammatory changes) differed significantly from the control groups. There was a significant correlation between exposure time and the total liver index values and the different reaction pattern indexes of treated fish (Spearman correlation; p>0.05). The present study indicates that dispersed oil is not more toxic, to livers of juvenile rabbit fish, than crude oil or dispersant. PMID- 21974903 TI - Contrast dispersal patterns as a predictor of clinical outcome with transforaminal epidural steroid injection for lumbar radiculopathy. AB - OBJECTIVE: To assess the relationship between epidural contrast dispersal patterns from lumbar transforaminal epidural steroid injections (TFESIs) and both immediate- and short-term pain reduction. We also investigated the effect of the grade of nerve root compression on contrast dispersal pattern and pain reduction. DESIGN: Retrospective review of data from a previous prospective study of outcomes after TFESI. SETTING: Academic spine and musculoskeletal clinic. PATIENT SAMPLE: Thirty-eight subjects who underwent single-level lumbar TFESI for unilateral lumbar radicular pain. METHODS: A retrospective assessment of a digital database of TFESIs for unilateral lumbar radicular pain. Type of contrast pattern was analyzed by 2 physiatrists as type I (tubular appearance); type II (nerve root visible as a filling defect); or type III (cloudlike appearance). Grade of nerve root compression on magnetic resonance also was analyzed by 2 physiatrists as grade I abutment, grade II displacement, or grade III entrapment. OUTCOME MEASURES: Effect of type of contrast pattern and grade of nerve root compression on change in Numeric Pain Rating Scale (NPRS) at time of injection (T1), 2 weeks after (T2), and 2 months after (T3). RESULTS: Mean decrease in NPRS at all time points was statistically significant with both types I and III contrast dispersal patterns. Groups with grades II and III nerve root compression had statistically significant reductions in NPRS at all time points. CONCLUSIONS: In this retrospective review we found that TFESIs can have an immediate beneficial effect on pain regardless of contrast pattern type or grade of nerve root compression. Subjects with higher grades of nerve root compression and a type I or III contrast pattern have significantly greater reductions in pain at 15 minutes, 2 weeks, and 2 months. Our findings are limited by methodological restrictions, and further confirmation with a prospective trial to review other possible associated factors is recommended. PMID- 21974904 TI - Bupivacaine injection leads to muscle force reduction and histologic changes in a murine model. AB - OBJECTIVE: To evaluate the effect of bupivacaine on muscle force and histology. We hypothesize that bupivacaine will worsen the muscle's physiological activity. SETTING: Controlled laboratory experiment. METHODS: Bupivacaine (0.5 mL, 0.5%) was injected into the mid belly and distal portions of the right gastrocnemius in 32 Wistar male rats (the left gastrocnemius was used as a control). After 5, 14, 21, and 28 days, in groups of 4, muscle force was evaluated and the animals were euthanized by an overdose of anesthetic for histologic evaluation. One-way analysis of variance was used to analyze data from force and weight measurements. Only the values of P < .05 were considered to be statistically significant. RESULTS: Bupivacaine causes a process of degeneration-regeneration of the muscle fibers and it also causes a reduction in muscle force, which is significant at 2 and 3 weeks and does not normalize at 4 weeks. The muscle injury is obvious after 5 days, and the degenerative process is predominant at 2 and 3 weeks. We found an increase in muscle mass in the acute phase and a decrease in muscle force. CONCLUSION: Although our results do not allow a direct clinical application, we believe that caution should be warranted when intramuscular bupivacaine is used. PMID- 21974905 TI - Segmental limb volume change as a predictor of the onset of lymphedema in women with early breast cancer. AB - OBJECTIVE: To demonstrate that segmental changes along the upper extremity occur before the onset of breast cancer-related lymphedema (BCRL). These changes may be subclinical in nature and may be predictive of the onset of chronic lymphedema. DESIGN: A retrospective subset analysis of a larger prospective cohort trial. PATIENT COHORT: A total of 196 patients provided consent and were enrolled in the prospective study. Subclinical lymphedema developed in 46 of these patients. Limb volume data were available for 45 of these 46 patients from visits before the onset of lymphedema and were used in this analysis. We compared this group with an age-matched control group without BCRL from the same cohort (n = 45). SETTING: Military hospital outpatient breast care center. METHODS: Women were enrolled and assessed preoperatively. Baseline measures of limb volume were obtained with the use of optoelectronic perometry, and reassessment was conducted at 1, 3, 6, 9, and 12 months postoperatively. BCRL was identified in 46 of 196 women at an average of 6.9 months postoperatively. A retrospective analysis was conducted in which we examined volume changes over four 10-cm segments of the limb at the visits before the onset of BCRL. By using repeated-measures multivariate analysis of variance, we compared segmental volumes between groups at preoperative baseline, time of diagnosis of BCRL, and time of follow-up after early intervention. Linear regression analysis was performed to determine the strength of the relationship between total limb volume change with segmental volumes at the time of diagnosis of BCRL. MAIN OUTCOME MEASUREMENTS: We hypothesized that segmental volume changes occur and can be measured in the limb before the onset of lymphedema. RESULTS: At arm segments 10-20 cm (P = .044) and 20-30 cm (P <.001), a significant volume increase was noted before the diagnosis of subclinical BCRL. Segmental volume changes correlated to the total limb volume (TLV) change. At segments 20-30 cm, the coefficient of determination was r(2) = 0.952, and at 10-20 cm it was r(2) = 0.845, suggesting that these segments predicted TLV changes. CONCLUSION: Serial interval assessment of limb volume segments may be an important clinical tool to detect early-onset lymphedema before TLV changes. PMID- 21974906 TI - Insulin-containing layer-by-layer films deposited on poly(lactic acid) microbeads for pH-controlled release of insulin. AB - Layer-by-layer (LbL) thin films containing insulin were deposited on the surface of biodegradable poly(lactic acid) (PLA) microbeads and the pH-triggered release of insulin was studied. The LbL films were successfully prepared by the alternate deposition of insulin and poly(vinyl sulfate) (PVS) or dextran sulfate (DS) at pH 4.0 through the electrostatic force of attraction between positively charged insulin and polyanions. The loading of insulin on the microbeads was dependent on the number of insulin layers and the type of polyanions used; higher insulin loading was observed for thicker films and when PVS was used as the polyanion. Insulin was released from the microbeads when they were exposed to neutral solution (pH 7.4) due to a loss of electrostatic attraction between the insulin and polyanions in the films, which in turn was caused by the charge reversal of insulin from positive to negative in the neutral medium. The pH threshold for insulin release was found to be pH 5.0-6.0. The released insulin retained its original secondary structure as evidenced by circular dichroism spectra. The insulin loaded on the microbeads was satisfactorily stable even in the presence of a digestive enzyme (pepsin) at pH 1.5. These results suggest a potential future use for insulin-loaded microbeads in the oral delivery of insulin. PMID- 21974907 TI - Amphiphilic comb-like polymer for harvest of conductive nano-cellulose. AB - In this study, electrically conductive bacterial cellulose (BC) was prepared by culturing Gluconacetobacter xylinus in a carbon nanotube (CNT)-dispersed medium. The CNTs were dispersed by adopting a non-covalent approach in the presence of non-ionic amphiphilic comb-like polymer (CLP). Specifically, the hydrophobic backbone of CLP was chemophysically attached to the surface of the CNTs and the hydrophilic side chains were released freely toward the medium in an aqueous environment. CLP-modified CNTs were stable and did not show any noticeable sediment, even after centrifugation at 15,000 rpm for 30 min. Notably, the dispersion solution of CLP-modified CNTs was stable at room temperature for several months because the long-range entropic repulsion among polymer-decorated tubes acted as a barrier to aggregation. The morphology of the BC membrane was studied by field-emission scanning electron microscopy. The presence of CLP bound to the CNT surface was characterized by Fourier transform infrared spectroscopy and the conductivity of the CNT-incorporated BC membrane was measured by four probe measurements. PMID- 21974908 TI - Preparation and surface properties of polyrotaxane-containing tri-block copolymers as a design for dynamic biomaterials surfaces. AB - A tri-block copolymer series containing hydrophilic polyrotaxane and hydrophobic poly(iso-butylmethacrylate) (PiBMA) segments was prepared by atom transfer radical polymerization (ATRP), starting from a pseudopolyrotaxane consisting of 2 bromoisobutyryl end-capped poly(ethylene glycol) (PEG) and alpha-cyclodextrin (alpha-CD) and followed by methylation. The dynamic wettability and molecular mobility of the copolymer surfaces were evaluated by dynamic contact angle (DCA) and quartz crystal microbalance with dissipation (QCM-D) measurements, respectively. The polyrotaxane tri-block copolymer surfaces were found to show pronounced dynamic wettability and molecular mobility compared to the control surfaces-a tri-block polymer consisting of PEG and PiBMA, and a PiBMA homopolymer suggesting that a polyrotaxane loop-like structure exists at the outermost surface in an aqueous environment and exhibits dynamic properties attributable to the possible mobile nature of hydrated alpha-CD molecules along the PEG backbone. Finally, excellent protein adsorption repellency was achieved on the polyrotaxane tri-block copolymer surface, presumably due to the mobile nature of the supramolecular architecture on the surface. PMID- 21974909 TI - pH-induced phase transition control of thermoresponsive nano-micelles possessing outermost surface sulfonamide moieties. AB - Diblock copolymer comprising thermoresponsive poly(N-isopropylacrylamide-co-N,N dimethylacrylamide) (PIPAAm-co-DMAAm) and hydrophobic poly(benzyl methacrylate) blocks was prepared by reversible addition-fragmentation chain transfer radical polymerization. Terminal functionalization of thermoresponsive blocks with either pH-responsive sulfadimethoxine (SD) or hydroxyl groups was performed through coupling reactions with thiol groups exposed by the aminolysis of dithiobenzoate groups located at P(IPAAm-co-DMAAm) termini. Outermost surface functionalized polymeric micelles were formed through the multi-assemblies of end-functional diblock copolymers with low critical micelle concentration (3.1-3.3 mg/L) regardless of their terminal groups. Variety of outermost surface functional groups had little influence on nano-scale diameters of approximately 19 nm at various pH values. Although the zeta-potentials of nonionic (phenyl and hydroxyl) surface micelles were independent of pH values ranged 8.1-5.4, those of SD surface polymeric micelles changed from -12 to -4 mV with reducing pH value, which caused by the protonation of surface SD units (pK(a)=6.2). In addition, lower critical solution temperature (LCST) of SD-surface micelles significantly shifted from 38.6 to 22.6 degrees C with lowering pH from 5.4 to 8.1. These pH induced lower LCST shifts were caused by extremely increasing surface hydrophobicity through the charge neutralization of SD moieties and the subsequent promoted dehydration of corona-forming polymer chains. These results indicated that the phase transition behavior of thermoresponsive nano-micelles was particularly controlled by modulating the properties of outermost surface chemistry via specific signals (e.g., pH, light, and biomolecular interaction). PMID- 21974910 TI - Design and in vitro evaluation of multiparticulate floating drug delivery system of zolpidem tartarate. AB - Zolpidem tartarate is a non-benzodiazepine, sedative-hypnotic, which finds its major use in various types of insomnia. The present work relates to development of multiparticulate floating drug delivery system based on gas generation technique to prolong the gastric residence time and to increase the overall bioavailability. Modified release dosage form of zolpidem tartarate adapted to release over a predetermined time period, according to biphasic profile of dissolution, where the first phase is immediate release phase for inducing the sleep and the second phase is modified release phase for maintaining the sleep up to 10 h. The system consists of zolpidem tartarate layered pellets coated with effervescent layer and polymeric membrane. The floating ability and in vitro drug release of the system were dependent on amount of the effervescent agent (sodium bicarbonate) layered onto the drug layered pellets, and coating level of the polymeric membrane (Eudragit((r)) NE 30D). The system could float completely within 5 min and maintain the floating over a period of 10 h. The multiparticulate floating delivery system of zolpidem tartarate with rapid floating and modified drug release was obtained. PMID- 21974911 TI - The adsorption of xyloglucan on cellulose: effects of explicit water and side chain variation. AB - The interaction between para-crystalline cellulose and the cross-linking glycan xyloglucan (XG) plays a central role for the strength and extensibility of plant cell walls. The coating of XGs on cellulose surfaces is believed to be one of the most probable interaction patterns. In this work, the effects of explicit water and side chain variation on the adsorption of XGs on cellulose are investigated by means of atomistic molecular dynamics simulations. The adsorption properties are studied in detail for three XGs on cellulose Ibeta 1-10 surface in aqueous environment, namely GXXXGXXXG, GXXLGXXXG, and GXXFGXXXG, which differ in the length and composition of one side chain. Our work shows that when water molecules are included in the theoretical model, the total interaction energies between the adsorbed XGs and cellulose are considerably smaller than in vacuo. Furthermore, in water environment the van der Waals interactions prevail over the electrostatic interactions in the adsorption. Variation in one side chain does not have significant influence on the interaction energy and the binding affinity, but does affect the equilibrium structural properties of the adsorbed XGs to facilitate the interaction between both the backbone and the side chain residues with the cellulose surface. Together, this analysis provides new insights into the nature of the XG-cellulose interaction, which helps to further refine current molecular models of the composite plant cell wall. PMID- 21974912 TI - Highly conductive, mechanically robust, and electrochemically inactive TiC/C nanofiber scaffold for high-performance silicon anode batteries. AB - Silicon has a high specific capacity of 4200 mAh/g as lithium-ion battery anodes, but its rapid capacity fading due to >300% volume expansion and pulverization presents a significant challenge for practical applications. Here we report a core-shell TiC/C/Si inactive/active nanocomposite for Si anodes demonstrating high specific capacity and excellent electrochemical cycling. The amorphous silicon layer serves as the active material to store Li(+), while the inactive TiC/C nanofibers act as a conductive and mechanically robust scaffold for electron transport during the Li-Si alloying process. The core-shell TiC/C/Si nanocomposite anode shows ~3000 mAh g(-1) discharge capacity and 92% capacity retention after 100 charge/discharge cycles. The excellent cycling stability and high rate performance could be attributed to the tapering of the nanofibers and the open structure that allows facile Li ion transport and the high conductivity and mechanical stability of the TiC/C scaffold. PMID- 21974913 TI - Visual field progression outcomes in glaucoma subtypes. AB - PURPOSE: To determine whether glaucoma subtype is an independent risk factor for visual field (VF) progression. METHODS: We reviewed the charts of glaucoma suspects and glaucoma patients seen in a referral practice between 1999 and 2009. Automated pointwise linear regression analysis determined the rates of VF change. A progression endpoint was determined when two or more adjacent test locations in the same hemifield showed a threshold sensitivity decline at a rate of >=1.0 dB/year with p < 0.01. RESULTS: We included 841 eyes (841 patients; mean age, 64.1 +/- 12.6 years; mean number of VF tests, 10.8 +/- 2.8; mean follow-up, 6.4 +/- 1.7 years). The glaucomatous group consisted of angle-closure glaucoma (76 eyes), juvenile primary open-angle glaucoma (37 eyes), normal-tension glaucoma (81 eyes), pigmentary glaucoma (34 eyes), primary open-angle glaucoma (275 eyes) and exfoliative glaucoma (XFG, 84 eyes). Normal-tension glaucoma eyes were more likely to present with beta-zone parapapillary atrophy and disc haemorrhage (p < 0.01). Exfoliative glaucoma eyes had the fastest rates of global VF change (-0.65 dB/year), as well as the highest mean, fluctuation, and peak intraocular pressure during follow-up (16.5, 3.0 and 22.0 mmHg, respectively) and reached a progression endpoint more frequently (40%). After adjusting for all covariates, including the glaucoma phenotype, there was no difference among groups regarding global rates of VF change and the risk of reaching a progression endpoint. CONCLUSIONS: Despite different clinical features, epidemiology and genetics, glaucoma phenotype is not an independent risk factor for VF progression. Rather, variations in well-known, reported risk factors remain important disease parameters that affect progression. PMID- 21974914 TI - Observational measure of implementation progress in community based settings: the Stages of Implementation Completion (SIC). AB - BACKGROUND: An increasingly large body of research is focused on designing and testing strategies to improve knowledge about how to embed evidence-based programs (EBP) into community settings. Development of strategies for overcoming barriers and increasing the effectiveness and pace of implementation is a high priority. Yet, there are few research tools that measure the implementation process itself. The Stages of Implementation Completion (SIC) is an observation based measure that is used to track the time to achievement of key implementation milestones in an EBP being implemented in 51 counties in 53 sites (two counties have two sites) in two states in the United States. METHODS: The SIC was developed in the context of a randomized trial comparing the effectiveness of two implementation strategies: community development teams (experimental condition) and individualized implementation (control condition). Fifty-one counties were randomized to experimental or control conditions for implementation of multidimensional treatment foster care (MTFC), an alternative to group/residential care placement for children and adolescents. Progress through eight implementation stages was tracked by noting dates of completion of specific activities in each stage. Activities were tailored to the strategies for implementing the specific EBP. RESULTS: Preliminary data showed that several counties ceased progress during pre-implementation and that there was a high degree of variability among sites in the duration scores per stage and on the proportion of activities that were completed in each stage. Progress through activities and stages for three example counties is shown. CONCLUSIONS: By assessing the attainment time of each stage and the proportion of activities completed, the SIC measure can be used to track and compare the effectiveness of various implementation strategies. Data from the SIC will provide sites with relevant information on the time and resources needed to implement MTFC during various phases of implementation. With some modifications, the SIC could be appropriate for use in evaluating implementation strategies in head-to-head randomized implementation trials and as a monitoring tool for rolling out other EBPs. PMID- 21974916 TI - Dosimetric comparison of liver tumour radiotherapy in all respiratory phases and in one phase using 4DCT. AB - PURPOSE: Delineation of target volume could be performed on all respiratory phases and radiation is delivered during free breathing cycle, or on the basis of one respiratory phase and deliver gated treatment choosing a specific phase for irradiation. We performed the comparison of both techniques in terms of target and normal tissue dose distributions. MATERIALS AND METHODS: We analysed 26 metastatic liver tumours using 4DCT to characterize tumour motion and to create treatment volumes: GITV4D was based on all 8 respiratory phases and GTVGAT was based on one specific phase. A 5mm automatic expansion was added to the GTVs to create PTVs. Two treatment plans were prepared to the total dose of 36 Gy in 3 fractions and dose-volume distributions were analysed for the target and organs at risk. Target motion along the superior-inferior direction was greatest with the mean of 1.1 cm +/- 0.3, and in the lateral the mean was 0.7 cm +/- 0.3. RESULTS: GTV and PTV volumes were larger in the 4D than in the GAT, mean 30.7 vs. 19.3 cm(3), and 66.7 vs. 45.1cm(3). We achieved similar dose coverage in PTV4D, for the 4D plan, and PTVGAT for the GAT plan, but a decrease in the average minimum dose to 17.8 Gy and the average mean dose to 35.3 Gy was found in PTV4D in the GAT plan. Radiotherapy delivered using GAT resulted in lower liver doses than using 4D with reduction of mean volume receiving 5 Gy by 6.5%+/-5, V(15Gy) by 4.5%+/-3.4, V(21Gy) by 3.4%+/-2.8 and reduction of mean kidney volume receiving 5 Gy by 9.1%+/-7.9, V(15Gy) by 4.1%+/-6.4, V(21Gy) by 3.2%+/-5.6. We also found correlations between PTV volume reduction with GAT, GTV motion and doses to normal tissues. CONCLUSIONS: Gated radiotherapy could potentially allow a reduction in PTV volumes from those delineated on all respiratory phases, maintaining acceptable target coverage. Smaller target volumes improve doses distribution in normal tissue especially in the liver and kidney, but also spinal cord and intestine. A significant correlation has been found between dose and volume reduction in the OARs and both GTV motion and PTV volume reduction. PMID- 21974915 TI - Symptomatic reactions, clinical outcomes and patient satisfaction associated with upper cervical chiropractic care: a prospective, multicenter, cohort study. AB - BACKGROUND: Observational studies have previously shown that adverse events following manipulation to the neck and/or back are relatively common, although these reactions tend to be mild in intensity and self-limiting. However, no prospective study has examined the incidence of adverse reactions following spinal adjustments using upper cervical techniques, and the impact of this care on clinical outcomes. METHODS: Consecutive new patients from the offices of 83 chiropractors were recruited for this practice-based study. Clinical outcome measures included 1) Neck pain disability index (100-point scale), 2) Oswestry back pain index (100-point scale), 3) 11-point numerical rating scale (NRS) for neck, headache, midback, and low back pain, 4) treatment satisfaction, and 5) Symptomatic Reactions (SR). Data were collected at baseline, and after approximately 2 weeks of care. A patient reaching sub-clinical status for pain and disability was defined as a follow-up score <3 NRS and <10%, respectively. A SR is defined as a new complaint not present at baseline or a worsening of the presenting complaint by >30% based on an 11-point numeric rating scale occurring <24 hours after any upper cervical procedure. RESULTS: A total of 1,090 patients completed the study having 4,920 (4.5 per patient) office visits requiring 2,653 (2.4 per patient) upper cervical adjustments over 17 days. Three hundred thirty- eight (31.0%) patients had SRs meeting the accepted definition. Intense SR (NRS >=8) occurred in 56 patients (5.1%). Outcome assessments were significantly improved for neck pain and disability, headache, mid-back pain, as well as lower back pain and disability (p <0.001) following care with a high level (mean = 9.1/10) of patient satisfaction. The 83 chiropractors administered >5 million career upper cervical adjustments without a reported incidence of serious adverse event. CONCLUSIONS: Upper cervical chiropractic care may have a fairly common occurrence of mild intensity SRs short in duration (<24 hours), and rarely severe in intensity; however, outcome assessments were significantly improved with less than 3 weeks of care with a high level of patient satisfaction. Although our findings need to be confirmed in subsequent randomized studies for definitive risk-benefit assessment, the preliminary data shows that the benefits of upper cervical chiropractic care may outweigh the potential risks. PMID- 21974917 TI - Impact of elective neck dissection on regional recurrence and survival in cN0 staged oral maxillary squamous cell carcinoma. AB - To evaluate the impact of elective neck dissection (END) on regional recurrence and survival in cN0 staged patients with maxillary squamous cell carcinoma (SCC). Eighty-six patients with maxillary SCC and clinically staged N0 cervical lymph nodes were evaluated in this single center retrospective study. Seventy-four of 86 patients were included in this analysis, of which 36 patients were treated with END, 38 without END. Following END, pathohistologically verified regional lymph-nodes in the initially cN0 neck were found in three (8%) patients. In both the +END and non-END group regional recurrences occurred exclusively in patients with T4 primaries. The overall regional recurrence rate was 17% in the +END and 18% in the non-END group, respectively. The 5-year overall survival rate for all tumor stages combined (T1-T4) was 86% in the +END group and 82% in the -END group. Within the patients groups with T4 tumors, 5-year overall survival was 81% for the +END group and 56% for the -END group. Over all tumor stages combined (T1 T4), END did not significantly improve overall survival rates and did not prevent the rate of regional recurrence in cN0 staged patients with maxillary alveolar, gingival and palatal SCC. However, in the subgroup of patients with locally advanced T4 tumors, their seemed to be a clear tendency towards improvement of overall survival in the END group. END can therefore be recommended for these patients. PMID- 21974918 TI - Mimicking natural superhydrophobic surfaces and grasping the wetting process: a review on recent progress in preparing superhydrophobic surfaces. AB - A typical superhydrophobic (ultrahydrophobic) surface can repel water droplets from wetting itself, and the contact angle of a water droplet resting on a superhydrophobic surface is greater than 150 degrees , which means extremely low wettability is achievable on superhydrophobic surfaces. Many superhydrophobic surfaces (both manmade and natural) normally exhibit micro- or nanosized roughness as well as hierarchical structure, which somehow can influence the surface's water repellence. As the research into superhydrophobic surfaces goes deeper and wider, it is becoming more important to both academic fields and industrial applications. In this work, the most recent progress in preparing manmade superhydrophobic surfaces through a variety of methodologies, particularly within the past several years, and the fundamental theories of wetting phenomena related to superhydrophobic surfaces are reviewed. We also discuss the perspective of natural superhydrophobic surfaces utilized as mimicking models. The discussion focuses on how the superhydrophobic property is promoted on solid surfaces and emphasizes the effect of surface roughness and structure in particular. This review aims to enable researchers to perceive the inner principles of wetting phenomena and employ suitable methods for creation and modification of superhydrophobic surfaces. PMID- 21974919 TI - Chlorine residuals and haloacetic acid reduction in rapid sand filtration. AB - It is quite rare to find biodegradation in rapid sand filtration for drinking water treatment. This might be due to frequent backwashes and low substrate levels. High chlorine concentrations may inhibit biofilm development, especially for plants with pre-chlorination. However, in tropical or subtropical regions, bioactivity on the sand surface may be quite significant due to high biofilm development--a result of year-round high temperature. The objective of this study is to explore the correlation between biodegradation and chlorine concentration in rapid sand filters, especially for the water treatment plants that practise pre-chlorination. In this study, haloacetic acid (HAA) biodegradation was found in conventional rapid sand filters practising pre-chlorination. Laboratory column studies and field investigations were conducted to explore the association between the biodegradation of HAAs and chlorine concentrations. The results showed that chlorine residual was an important factor that alters bioactivity development. A model based on filter influent and effluent chlorine was developed for determining threshold chlorine for biodegradation. From the model, a temperature independent chlorine concentration threshold (Cl(threshold)) for biodegradation was estimated at 0.46-0.5mgL(-1). The results imply that conventional filters with adequate control could be conducive to bioactivity, resulting in lower HAA concentrations. Optimizing biodegradable disinfection by product removal in conventional rapid sand filter could be achieved with minor variation and a lower-than-Cl(threshold) influent chlorine concentration. Bacteria isolation was also carried out, successfully identifying several HAA degraders. These degraders are very commonly seen in drinking water systems and can be speculated as the main contributor of HAA loss. PMID- 21974921 TI - Self-organized TiO2 nanorod arrays on glass substrate for self-cleaning antireflection coatings. AB - Herein we report the direct fabrication of TiO(2) subwavelength structures with 1 dimensional TiO(2) nanorods on glass substrate through solvothermal process to form self-cleaning antireflection coatings. TiO(2) precursor solutions with different solvent constituents create TiO(2) nanorods with much different morphologies grown on glass substrates. Apiculate TiO(2) nanorods with vertical orientation are grown on the glass substrate which is solvothermally treated in the precursor solution containing ethylene glycol. This glass substrate exhibit the highest transmittance of 70-85% in the range of 520-800 nm and negligible absorption in visible light region (400-800 nm). Furthermore, the TiO(2) nanorod arrays show high hydrophobicity and photocatalytic degradation ability which offer the glass substrate self-cleaning properties for both hydrophilic and oily contaminants. PMID- 21974922 TI - Surface mercapto engineered magnetic Fe3O4 nanoadsorbent for the removal of mercury from aqueous solutions. AB - In this study, mercapto-functionalized nano-Fe(3)O(4) magnetic polymers (SH Fe(3)O(4)-NMPs) have been prepared and characterized by transmission electron microscopy (TEM), X-ray diffractometer (XRD), vibrating sample magnetometer (VSM), thermogravimetry and differential thermogravimetry analyses (TG-DTA), as well as Fourier-transformed infrared spectroscopy (FTIR). The adsorptive characteristics of the SH-Fe(3)O(4)-NMPs intended for removal of mercury (II) were deeply studied. The results showed that the adsorption efficiency increased with pH increasing and reached a plateau at pH above 3.0. The adsorption data obtained at the optimized condition, i.e., 308 K and pH of 3.0, were well fitted with the Freundlich isotherm. The adsorption of Hg(II) reached equilibrium within 60 min. Thermodynamic parameters such as DeltaH(theta), DeltaS(theta) and DeltaG(theta) suggested that the adsorption processes of Hg(II) onto the SH Fe(3)O(4)-NMPs were endothermic and entropy favored in nature, with DeltaH(theta) at 30.31 kJ mol(-1), DeltaS(theta) at 111.41 J mol(-1) K(-1). The effects of mercury salts, i.e., Hg(NO(3))(2), HgSO(4), and different acids, were also deeply investigated and showed that the adsorption capacity of Hg(II) onto the SH Fe(3)O(4)-NMPs decreased when Cl(-) existed. PMID- 21974923 TI - Targeted therapy of SMMC-7721 liver cancer in vitro and in vivo with carbon nanotubes based drug delivery system. AB - A new type of drug delivery system (DDS) involved chitosan (CHI) modified single walled carbon nanotubes (SWNTs) for controllable loading/release of anti-cancer doxorubicin (DOX) was constructed. CHI was non-covalently wrapped around SWNTs, imparting water-solubility and biocompatibility to the nanotubes. Folic acid (FA) was also bounded to the outer CHI layer to realize selective killing of tumor cells. The targeting DDS could effectively kill the HCC SMMC-7721 cell lines and depress the growth of liver cancer in nude mice, showing superior pharmaceutical efficiency to free DOX. The results of the blood routine and serum biochemical parameters, combined with the histological examinations of vital organs, demonstrating that the targeting DDS had negligible in vivo toxicity. Thus, this DDS is promising for high treatment efficacy and low side effects for future cancer therapy. PMID- 21974924 TI - Facile synthesis of polyoxometalate-thionine composite via direct precipitation method and its photocatalytic activity for degradation of rhodamine B under visible light. AB - (TH)(3)PW(12) (TH=thionine, PW(12)=PW(12)O(40)(3-)) composite was prepared by direct precipitation of TH and PW(12). The (TH)(3)PW(12) was characterized via UV vis spectrum, FT-IR, SEM, and BET surface area. PW(12) was intact during the precipitation process. The composite has a bar-like shape and relatively large surface area (Langmuir surface of (TH)(3)PW(12) was 31.59 m(2)g(-1), BET surface was 20.26 m(2)g(-1)). Using the material as the photocatalyst, rhodamine B (RhB) was efficiently bleached and mineralized under visible light irradiation (lambda>420 nm). The kinetics of the photodecomposition follow the first-order reaction. The (TH)(3)PW(12) catalyst can be easily separated from the reaction system and has good stability for reuse. PMID- 21974925 TI - Specific interactions between nucleolipid doped liposomes and DNA allow a more efficient polynucleotide condensation. AB - The interactions between cationic liposomes doped with the anionic nucleolipid 1,2-dipalmitoyl-sn-glycero-3-cytidine diphosphate (DP-Cyt) and deoxyribonucleic acid (DNA) were investigated. Toward this goal, new liposomal and lipoplex formulations characterized by the presence of the anionic amphiphile DP-Cyt were proposed. The effects of incorporation of the cytosine functionalized lipid DP Cyt into the cationic bilayers were analyzed by means of electrophoretic mobility, dynamic light scattering (DLS) and fluorescence spectroscopy techniques. These approaches allowed us to follow the DNA condensation process and to identify specific electrokinetic characteristics of liposome and DNA liposome complexes formation. Specifically, DP-Cyt liposomes and DNA were shown to form electrically stable or unstable complexes depending on the charge ratio between the phosphate group of DNA and the cationic lipid. Remarkably, a prominent role for DP-Cyt in enhancing the DNA binding capacity on liposomes was demonstrated. Zeta potential experiments performed on systems with different liposomes/DNA ratio showed that the value of the charge neutralization point is a function of the content of the incorporated DP-Cyt. As a whole, our data demonstrate that the association of cationic DP-Cyt doped liposomes with DNA is driven by both electrostatic interaction and additional specific interactions at the polar head level based on the cytidine nucleobase. PMID- 21974926 TI - Effects of home-based rehabilitation on health-related quality of life and psychological status in Chinese patients recovering from acute myocardial infarction. AB - OBJECTIVE: This study evaluated the effects of a home-based rehabilitation program for Chinese patients with myocardial infarction in terms of health related quality of life and psychological status. METHODS: This was a randomized, controlled trial with data collected at 2 university-affiliated public general hospitals in Xian (Shaanxi Province, People's Republic of China). One hundred and sixty patients with a myocardial infarction were randomly assigned to either the interventional group (a home-based cardiac rehabilitation program using a self help manual) or the control group (usual care). Health-related quality of life (generic, Chinese Short Form 36-Item Health Survey; disease-specific, Chinese Myocardial Infarction Dimensional Assessment Scale) and psychological status (the Chinese Hospital Anxiety and Depression Scale) were measured at baseline, program completion (6 weeks), and 3 and 6 months after hospital discharge. RESULTS: Significant differences were evident in the main outcomes when the home-based group was compared with the usual care group at 6 weeks, 3 months, and 6 months. The home-based group had significantly higher scores on 4 of the 8 domains of the Chinese Short Form 36-Item Health Survey and on 3 of the 7 dimensions of the Chinese Myocardial Infarction Dimensional Assessment Scale, with significantly lower scores on the anxiety, but not the depression, subscale of the Chinese Hospital Anxiety and Depression Scale. CONCLUSIONS: A simple, home-based cardiac rehabilitation program for patients with acute myocardial infarction, using a self-help manual, improves health-related quality of life and reduces anxiety. It appears feasible and acceptable, and does not produce inferior outcomes compared with usualcare in China. PMID- 21974927 TI - Regional contrast agent quantification in a mouse model of myocardial infarction using 3D cardiac T1 mapping. AB - BACKGROUND: Quantitative relaxation time measurements by cardiovascular magnetic resonance (CMR) are of paramount importance in contrast-enhanced studies of experimental myocardial infarction. First, compared to qualitative measurements based on signal intensity changes, they are less sensitive to specific parameter choices, thereby allowing for better comparison between different studies or during longitudinal studies. Secondly, T1 measurements may allow for quantification of local contrast agent concentrations. In this study, a recently developed 3D T1 mapping technique was applied in a mouse model of myocardial infarction to measure differences in myocardial T1 before and after injection of a liposomal contrast agent. This was then used to assess the concentration of accumulated contrast agent. MATERIALS AND METHODS: Myocardial ischemia/reperfusion injury was induced in 8 mice by transient ligation of the LAD coronary artery. Baseline quantitative T1 maps were made at day 1 after surgery, followed by injection of a Gd-based liposomal contrast agent. Five mice served as control group, which followed the same protocol without initial surgery. Twenty-four hours post-injection, a second T1 measurement was performed. Local DeltaR1 values were compared with regional wall thickening determined by functional cine CMR and correlated to ex vivo Gd concentrations determined by ICP MS. RESULTS: Compared to control values, pre-contrast T1 of infarcted myocardium was slightly elevated, whereas T1 of remote myocardium did not significantly differ. Twenty-four hours post-contrast injection, high DeltaR1 values were found in regions with low wall thickening values. However, compared to remote tissue (wall thickening > 45%), DeltaR1 was only significantly higher in severe infarcted tissue (wall thickening < 15%). A substantial correlation (r = 0.81) was found between CMR-based DeltaR1 values and Gd concentrations from ex vivo ICP MS measurements. Furthermore, regression analysis revealed that the effective relaxivity of the liposomal contrast agent was only about half the value determined in vitro. CONCLUSIONS: 3D cardiac T1 mapping by CMR can be used to monitor the accumulation of contrast agents in contrast-enhanced studies of murine myocardial infarction. The contrast agent relaxivity was decreased under in vivo conditions compared to in vitro measurements, which needs consideration when quantifying local contrast agent concentrations. PMID- 21974928 TI - Thyroid hormone drives fetal cardiomyocyte maturation. AB - Tri-iodo-l-thyronine (T(3)) suppresses the proliferation of near-term serum stimulated fetal ovine cardiomyocytes in vitro. Thus, we hypothesized that T(3) is a major stimulant of cardiomyocyte maturation in vivo. We studied 3 groups of sheep fetuses on gestational days 125-130 (term ~145 d): a T(3)-infusion group, to mimic fetal term levels (plasma T(3) levels increased from ~0.1 to ~1.0 ng/ml; t(1/2)~24 h); a thyroidectomized group, to produce low thyroid hormone levels; and a vehicle-infusion group, to serve as intact controls. At 130 d of gestation, sections of left ventricular freewall were harvested, and the remaining myocardium was enzymatically dissociated. Proteins involved in cell cycle regulation (p21, cyclin D1), proliferation (ERK), and hypertrophy (mTOR) were measured in left ventricular tissue. Evidence that elevated T(3) augmented the maturation rate of cardiomyocytes included 14% increased width, 31% increase in binucleation, 39% reduction in proliferation, 150% reduction in cyclin D1 protein, and 500% increase in p21 protein. Increased expression of phospho-mTOR, ANP, and SERCA2a also suggests that T(3) promotes maturation and hypertrophy of fetal cardiomyocytes. Thyroidectomized fetuses had reduced cell cycle activity and binucleation. These findings support the hypothesis that T(3) is a prime driver of prenatal cardiomyocyte maturation. PMID- 21974930 TI - Two strikes: limited NIH R55 and R56 retooling funds and abolishment of the A2 grant mechanism. AB - The U.S. National Institutes of Health (NIH) are facing significant budgetary challenges as a result of the current economic climate. The recent sunset of investigator-initiated R01-type research grants after one revised submission, coupled with the present lack of an NIH retooling funding mechanism for such grant applicants, creates a concerning risk that talented and well-trained investigators may be forced to give up their research careers. Existing NIH retooling mechanisms include the R55 Shannon Award, which was established in 1991 and was essentially replaced in 2005 by the R56 award. There is an urgent need to either significantly expand the R55/R56 mechanisms and definition of NIH grant bridging/retooling support for unfunded meritorious proposals or introduce a new mechanism that provides specific support to investigators with competitive but unfunded R01 revised grants. An expanded retooling funding mechanism deserves implementation during continuing assessment of whether allowance of only one revision of research proposals has achieved its initial intended goals. PMID- 21974929 TI - Fetal progenitor cells naturally transferred through pregnancy participate in inflammation and angiogenesis during wound healing. AB - The phenotype and fate of fetal microchimeric cells transfered into the maternal circulation during pregnancy are not well described. Since progenitors from distal sites mobilize during wound healing, we analyzed the recruitment and plasticity of fetal progenitors into maternal wounds. Wounds were generated on normal and bleomycin-induced fibrotic skin of parous or pregnant wild-type females with fluorescent GFP(+) fetuses. Analyses were performed on skin and blood specimens through PCR, immunohistochemistry, and flow cytometry. Controls consisted of parous and pregnant females without wounds and virgin females with wounds. Fetal cells were detected in all skin specimens of parous mice as long as healing was not achieved. During early stages of wound healing, fetal cells expressed mainly leukocyte markers, while in later phases endothelial markers prevailed. Fetally derived vessels connected to maternal circulation were also found, demonstrating the transfer of fetal endothelial progenitor cells. Wounding mobilized fetal CD34(+)ckit(-) cells into the blood during pregnancy. Most of this population was CD11b(-)VEGFR2(-). Another part was CD11b(+) with a fraction expressing VEGFR2. VEGFa-spiked Matrigel plugs partially mimicked this fetal progenitor recruitment and mobilization into the blood. In summary, fetal cells that mobilize in response to wounding are mainly progenitor cells and participate in angiogenesis and inflammation. PMID- 21974931 TI - A novel treatment strategy for ovarian cancer based on immunization against zona pellucida protein (ZP) 3. AB - We tested the principle of treating malignant ovarian tumors by vaccination against their ectopically expressed protein, zona pellucida glycoprotein (ZP) 3, using as the experimental model the granulosa cell tumors that develop in transgenic mice expressing the simian virus 40 T-antigen under the inhibin-alpha promoter (inhalpha/Tag). We found high ZP3 expression in granulosa cell tumors of the transgenic mice, in human surface ovarian cancer and granulosa cell lines, and in human granulosa cell tumors and their metastases. Early preventive immunization (between 2 and 5.5 mo of age) of transgenic mice with recombinant human (rh) ZP3 prevented ovarian tumorigenesis, and delayed therapeutic immunization (between 4.5 and 7 mo) reduced weights of existing tumors by 86 and 75%, respectively (P<0.001), compared to vehicle-treated control mice. No objective side effects of the immunizations were observed. Liver metastases were found in nontreated/vehicle-treated controls (n=7/39), but none following active rhZP3 immunizations (n=0/36; P<0.05). Immunization with rhZP3 was highly effective, as demonstrated by the induction of anti-ZP3 antibodies, as well as proliferative responses to the ZP3 antigen. These results signal rhZP3 immunization as a novel strategy to be developed for the immunotherapy of ovarian granulosa cell tumors, as well as for that of other malignancies that may express ZP3. PMID- 21974932 TI - Nuclear PLCs affect insulin secretion by targeting PPARgamma in pancreatic beta cells. AB - Type 2 diabetes is a heterogeneous disorder caused by concomitant impairment of insulin secretion by pancreatic beta cells and of insulin action in peripheral target tissues. Studies with inhibitors and agonists established a role for PLC in the regulation of insulin secretion but did not distinguish between effects due to nuclear or cytoplasmic PLC signaling pathways that act in a distinct fashion. We report that in MIN6 beta cells, PLCbeta1 localized in both nucleus and cytoplasm, PLCdelta4 in the nucleus, and PLCgamma1 in the cytoplasm. By silencing each isoform, we observed that they all affected glucose-induced insulin release both at basal and high glucose concentrations. To elucidate the molecular basis of PLC regulation, we focused on peroxisome proliferator activated receptor-gamma (PPARgamma), a nuclear receptor transcription factor that regulates genes critical to beta-cell maintenance and functions. Silencing of PLCbeta1 and PLCdelta4 resulted in a decrease in the PPARgamma mRNA level. By means of a PPARgamma-promoter-luciferase assay, the decrease could be attributed to a PLC action on the PPARgamma-promoter region. The effect was specifically observed on silencing of the nuclear and not the cytoplasmic PLC. These findings highlight a novel pathway by which nuclear PLCs affect insulin secretion and identify PPARgamma as a novel molecular target of nuclear PLCs. PMID- 21974933 TI - The changing burden of infectious disease in Europe. AB - Infectious diseases continue to pose major public health challenges in developed, as well as developing, countries. The European Academies Science Advisory Council aims to integrate multidisciplinary analyses to define priorities for European surveillance of new, growing, or potential threats from antimicrobial resistance, vector-borne disease, and pandemic influenza. There is a concomitant need to apply such knowledge toward the development of improved health care and robust policies. We discuss how translational medicine can bridge these global issues by helping to mobilize resources between academia, industry, health care services, and policy-makers. PMID- 21974934 TI - Striking a balance between feasible and realistic biological models. AB - The fusion of empirical science with large-scale computing platforms has allowed rapid advances in our ability to model physiological and pathophysiological processes in silico. In this week's issue of Science Translational Medicine, Tran et al. present a simple framework for the quantitative modeling of oncogene addiction that provides mechanistic insights into tumor biology. PMID- 21974935 TI - Increased gene dosage of Ube3a results in autism traits and decreased glutamate synaptic transmission in mice. AB - People with autism spectrum disorder are characterized by impaired social interaction, reduced communication, and increased repetitive behaviors. The disorder has a substantial genetic component, and recent studies have revealed frequent genome copy number variations (CNVs) in some individuals. A common CNV that occurs in 1 to 3% of those with autism--maternal 15q11-13 duplication (dup15) and triplication (isodicentric extranumerary chromosome, idic15)--affects several genes that have been suggested to underlie autism behavioral traits. To test this, we tripled the dosage of one of these genes, the ubiquitin protein ligase Ube3a, which is expressed solely from the maternal allele in mature neurons, and reconstituted the three core autism traits in mice: defective social interaction, impaired communication, and increased repetitive stereotypic behavior. The penetrance of these autism traits depended on Ube3a gene copy number. In animals with increased Ube3a gene dosage, glutamatergic, but not GABAergic, synaptic transmission was suppressed as a result of reduced presynaptic release probability, synaptic glutamate concentration, and postsynaptic action potential coupling. These results suggest that Ube3a gene dosage may contribute to the autism traits of individuals with maternal 15q11-13 duplication and support the idea that increased E3A ubiquitin ligase gene dosage results in reduced excitatory synaptic transmission. PMID- 21974936 TI - Neutrophil-derived cathelicidin protects from neointimal hyperplasia. AB - Percutaneous transluminal angioplasty with stent implantation is used to dilate arteries narrowed by atherosclerotic plaques and to revascularize coronary arteries occluded by atherothrombosis in myocardial infarction. Commonly applied drug-eluting stents release antiproliferative or anti-inflammatory agents to reduce the incidence of in-stent stenosis. However, these stents may still lead to in-stent stenosis; they also show increased rates of late stent thrombosis, an obstacle to optimal revascularization possibly related to endothelial recovery. Here, we examined the contribution of neutrophils and neutrophilic granule proteins to arterial healing after injury. We found that neutrophil-borne cathelicidin (mouse CRAMP, human LL-37) promoted reendothelization and thereby limited neointima formation after stent implantation. We then translated these findings to an animal model using a neutrophil-instructing, biofunctionalized, miniaturized Nitinol stent coated with LL-37. This stent reduced in-stent stenosis in a mouse model of atherosclerosis, suggesting that LL-37 may promote vascular healing after interventional therapy. PMID- 21974938 TI - Liver biopsy is a superior diagnostic method in some patients showing the typical laboratory features of autoimmune hepatitis. AB - AIMS: To investigate whether liver diseases other than autoimmune hepatitis (AIH) can present with the typical features of AIH, and to determine the impact of liver biopsy for differentiating AIH from these conditions. PATIENTS AND METHODS: The study used data collected at Hacettepe university hospital and numune education and research hospital from 2007 to 2011. The clinical, laboratory and histological findings of patients diagnosed with non-alcoholic steatohepatitis, drug-induced liver injury, primary biliary cirrhosis, primary sclerosing cholangitis, hemochromatosis and Wilson's disease were evaluated to identify those who presented with the typical features of AIH, but had no liver histology compatible with or suggestive of AIH. RESULTS: A total of 386 patients were evaluated, and four patients with typical features of AIH were identified. Three patients were positive for antinuclear antibodies, and one was positive for smooth muscle antibodies. Also, all four had increased levels of immunoglobulin G, and aminotransferase levels that were five times above the upper limit. According to simplified AIH criteria, all patients had a score of 6, indicating probable AIH. On liver biopsy, two patients were diagnosed with non-alcoholic steatohepatitis, another with drug-induced liver injury and a further one with primary biliary cirrhosis. CONCLUSION: Liver diseases other than AIH can present with the typical laboratory features of AIH and, without liver biopsy, it is difficult to distinguish AIH than these conditions. Although histological findings have little impact on patients' management and outcomes, for a definitive diagnosis of AIH, liver biopsy is essential and should be performed in all patients in whom it is suitable and not contraindicated. PMID- 21974939 TI - To determine the level of satisfaction among medical students of a public sector medical university regarding their academic activities. AB - BACKGROUND: An ongoing evaluation system is essential to determine if the academic system in place has worked to produce a better product, hence the objective of our study was to evaluate the satisfaction level among medical students regarding their academic teaching and assessment method and what measures will they suggest for the future to rectify the current situation.This questionnaire based cross sectional study was conducted in a public sector medical university from February to July 2010. A well structured questionnaire was administered to a random sample of 375 final year medical students. However 292 of the students provided informed consent and filled in the questionnaire which included their demographic profile as well as questions in line with the study objective. Data was entered in a Statistical Package for Social Sciences (SPSS version.16) and analyzed using descriptive statistics. FINDINGS: The male to female ratio in our study was 1:2. Most of the students (57.2%) were dissatisfied with the quality of teaching in the university. Fifty-seven percent of the participants believed that the current standard of their institute were not at par with those of international medical universities. BCQ's were the mode of examination questions preferred by the majority of the students. Most of the students (66.1%) wanted the university to conduct career planning seminars to help them plan their career. CONCLUSIONS: These results suggest that the students of public sector medical universities are unsatisfied from current academic facilities and teaching activities. Students recommend increased emphasis on better lectures and practical training as well as a need to incorporate career planning sessions for the students to help plan them their future career paths. PMID- 21974937 TI - Survival and death signals can predict tumor response to therapy after oncogene inactivation. AB - Cancers can exhibit marked tumor regression after oncogene inhibition through a phenomenon called "oncogene addiction." The ability to predict when a tumor will exhibit oncogene addiction would be useful in the development of targeted therapeutics. Oncogene addiction is likely the consequence of many cellular programs. However, we reasoned that many of these inputs may converge on aggregate survival and death signals. To test this, we examined conditional transgenic models of K-ras(G12D)--or MYC-induced lung tumors and lymphoma combined with quantitative imaging and an in situ analysis of biomarkers of proliferation and apoptotic signaling. We then used computational modeling based on ordinary differential equations (ODEs) to show that oncogene addiction could be modeled as differential changes in survival and death intracellular signals. Our mathematical model could be generalized to different imaging methods (computed tomography and bioluminescence imaging), different oncogenes (K ras(G12D) and MYC), and several tumor types (lung and lymphoma). Our ODE model could predict the differential dynamics of several putative prosurvival and prodeath signaling factors [phosphorylated extracellular signal-regulated kinase 1 and 2, Akt1, Stat3/5 (signal transducer and activator of transcription 3/5), and p38] that contribute to the aggregate survival and death signals after oncogene inactivation. Furthermore, we could predict the influence of specific genetic lesions (p53-/-, Stat3-d358L, and myr-Akt1) on tumor regression after oncogene inactivation. Then, using machine learning based on support vector machine, we applied quantitative imaging methods to human patients to predict both their EGFR genotype and their progression-free survival after treatment with the targeted therapeutic erlotinib. Hence, the consequences of oncogene inactivation can be accurately modeled on the basis of a relatively small number of parameters that may predict when targeted therapeutics will elicit oncogene addiction after oncogene inactivation and hence tumor regression. PMID- 21974941 TI - Operational conditions: legal capacity of a patient soldier refusing medical treatment. AB - Using a three-dimensional ethical role-specific model, this article considers the dual loyalty conflict between following military orders and professional codes of practice in an operational military environment when a patient soldier refuses life-saving medical treatment and where their legal capacity is questionable. The article suggests that although every competent patient has the right to refuse medical treatment even though they may die as a consequence. Ordinarily, it is unethical to exert any undue influence on a patient to accept medical treatment, in a military operational environment where attack from the enemy is likely, it may be reasonable and understandable to exert undue influence over a patient when they lack legal capacity. PMID- 21974940 TI - Ethical conflicts with hospitals: the perspective of nurses and physicians. AB - Nurses and physicians may experience ethical conflict when there is a difference between their own values, their professional values or the values of their organization. The distribution of limited health care resources can be a major source of ethical conflict. Relatively few studies have examined nurses' and physicians' ethical conflict with organizations. This study examined the research question 'What are the organizational ethical conflicts that hospital nurses and physicians experience in their practice?' We interviewed 34 registered nurses, 10 nurse managers, and 31 physicians as part of a larger study, and asked them to describe their ethical conflicts with organizations. Through content analysis, we identified themes of nurses' and physicians' ethical conflict with organizations and compared the themes for nurses with those for physicians. PMID- 21974942 TI - Changes in how ICU nurses perceive the DNR decision and their nursing activity after implementing it. AB - This study investigated the perceptions and attitudes of ICU nurses towards the 'do not resuscitate' (DNR) decision and changes in their nursing activities after implementation of the DNR decision in South Korea. A data survey was conducted in South Korea between August and October 2008, with a convenience sample of 252 ICU nurses who had more than one year of clinical experience. The data were collected via a self-administered questionnaire. Most of the nurses perceived the necessity of the DNR decision in cases where there would be no chance of patient recovery despite massive efforts. Very few of the nurses' activities changed, either passively or actively, after implementation of the DNR decision. Moreover, the findings of this research provide suggestions for the future direction of the DNR decision and ethical nursing guidelines in South Korea. Further investigations are needed for the development of decision-making skills and intervention guidelines for end-of-life nursing. PMID- 21974943 TI - Frequency and burden with ethical conflicts and burnout in nurses. AB - Many studies examine a stressors-professional burnout (PB) relation, but only few consider the role of ethical conflicts (ECs) in this context. The aim of this study was to characterize ECs' frequency and level of burden with them among nurses and to establish the relations between ECs' frequency, burden and PB. One hundred nurses participated in this study. ECs' frequency and burden were tested with an originally developed questionnaire. PB was examined with Maslach Burnout Inventory. Most frequent ECs concerned a nurse-patient relationship. PB was positively related to ECs' frequency (r = .54; p = .001) and burden (r = .22; p = .03). Frequency of specific conflict did not imply burden with it and vice versa. ECs' frequency seems more important for PB than a level of burden with them. The most frequent and the most burdening conflicts may lead to development of PB but the less frequent and less burdening ones are also dangerous. PMID- 21974944 TI - Orthodox Jewish perspectives on withholding and withdrawing life-sustaining treatment. AB - The Jewish religious tradition summons its adherents to save life. For religious Jews preservation of life is the ultimate religious commandment. At the same time Jewish law recognizes that the agony of a moribund person may not be stretched. When the time to die has come this has to be respected. The process of dying should not needlessly be prolonged. We discuss the position of two prominent Orthodox Jewish authorities - the late Rabbi Moshe Feinstein and Rabbi J David Bleich - towards the role of life-sustaining treatment in end-of-life care. From the review, the characteristic halachic and heterogeneous character of Jewish ethical reasoning appears. The specificity of Jewish dealing with ethical dilemmas in health care indicates the importance for contemporary healthcare professionals of providing care which is sensitive to a patient's culture and worldview. PMID- 21974945 TI - Rare gallbladder adenomyomatosis presenting as atypical cholecystitis: case report. AB - BACKGROUND: Gallbladder adenomyomatosis is a benign condition characterized by hyperplastic change in the gallbladder wall and overgrowth of the mucosa because of an unknown cause. Patients with gallbladder adenomyomatosis usually present with abdominal pain. However, we herein describe a case of a patient with gallbladder adenomyomatosis who did not present with abdominal pain, but with only fever. CASE PRESENTATION: A 34-year-old man presented to our hospital with a fever. No abdominal discomfort was declared. His physical examination showed no abnormalities. Ultrasound of the abdomen revealed thickness of the gallbladder. Acute cholecystitis was diagnosed. The fever persisted even after 1 week of antibiotic therapy. Magnetic resonance imaging of the abdomen showed gallbladder adenomyomatosis with intramural Rokitansky-Aschoff sinuses. Exploratory laparotomy with cholecystectomy was performed. The fever recovered and no residual symptoms were reported at the 3-year follow-up. CONCLUSIONS: Gallbladder adenomyomatosis can present with fever as the only symptom. Although the association between gallbladder adenomyomatosis and malignancy has yet to be elucidated, previous reports have shown a strong association between gallbladder carcinoma and a subtype of gallbladder adenomyomatosis. Surgical intervention remains the first-choice treatment for patients with gallbladder adenomyomatosis. PMID- 21974946 TI - Molecular taxonomic relationships of Psoroptes and Chorioptes mites from China based on COI and 18S rDNA gene sequences. AB - In this present study, the mitochondrial DNA gene cytochrome coxidase subunit I (COI) and the small subunit ribosomal RNA (18S rDNA) gene were used to determine the taxonomic relationships of Psoroptes and Chorioptes mites from China. The neighbor-joining and maximum-parasimony approach were used to evaluate the evolutionary relatedness among different hosts in the genera Psoroptes and Chorioptes. Phylogenetic analysis showed that Psoroptes cuniculi and Psoroptes natalensis may be two different species within the genus Psoroptes, and Chorioptes texanus and Chorioptes panda are different species within the genus Chorioptes. PMID- 21974947 TI - First report of Lagochilascaris (Nematoda: Ascarididae) eggs in a public park in Southern Brazil. AB - Public parks, especially in developing countries, are places where stray animals run free and may contaminate the environment with different species of parasites. In an evaluation of environmental sanitation of these sites, soil samples were collected monthly from public parks in the Pelotas city, Rio Grande do Sul State, Southern Brazil. Eggs of the nematode Lagochilascaris sp. were found in a public playground. This is the first report of identification of this nematode in Southern Brazil. PMID- 21974948 TI - The first detection of Echinococcus multilocularis in slaughtered pigs in Poland. AB - Alveolar echinococcosis is a serious zoonosis caused by the larval stage of Echinococcus multilocularis. Pigs, as humans, can play the role of non-specific intermediate hosts of this parasite. Detection of E. multilocularis in swine can be taken as an indicator of infection risk for humans. This paper presents the first cases where E. multilocularis larval forms have been detected in pigs in Poland. A total of 256 pig livers with different lesions were collected from slaughterhouses in southern Poland and examined by nested PCR method. Three of them were identified as E. multilocularis positive. They contained noticeable spherical nodular whitish forms on the surface of the liver, recessed partially into the liver tissue. In two cases only single lesions (3mm and 6mm in diameter) were found, while in one case numerous (eight) lesions (2mm in diameter) were found. PCR E. multilocularis identification was confirmed by sequencing and comparison with the GenBank database. PMID- 21974949 TI - Discovery of a new class of glucosylceramide synthase inhibitors. AB - A novel series of potent inhibitors of glucosylceramide synthase are described. The optimization of biochemical and cellular potency as well as ADME properties led to compound 23c. Broad tissue distribution was obtained following oral administration to mice. Thus 23c could be another useful tool compound for studying the effects of GCS inhibition in vitro and in vivo. PMID- 21974950 TI - A fluorescent probe for GM1 gangliosidosis related beta-galactosidase: N (dansylamino)hexylaminocarbonylpentyl-1,5-dideoxy-1,5-imino-D-galactitol. AB - N-(Dansylamino)hexylaminocarbonylpentyl-1,5-dideoxy-1,5-imino-D-galactitol, a strong competitive inhibitor of beta-galactosidase, enhances residual beta galactosidase activities in fibroblasts and serves as lead en route to diagnostic compounds for tracking the fate of mutant beta-gal as well as aberrant GM1 gangliosides by live cell imaging. PMID- 21974951 TI - Synthesis and anti-HIV-1 activity of 4-substituted-7-(2'-deoxy-2'-fluoro-4'-azido beta-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine analogues. AB - Three novel 4-subsituted-7-(2'-deoxy-2'-fluoro-4'-azido-beta-D ribofuranosyl)pyrrolo[2,3-d]pyrimidine analogues were designed, synthesized, and tested for their anti-HIV-1 activity. Initial biological studies indicated that among these pyrrolo[2,3-d]pyrimidine ribonucleoside analogues, 4-amino-7-(2' deoxy-2'-fluoro-4'-azido-beta-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine 10 exhibited the most potent anti-HIV-1 activity (EC(50)=0.5+/-0.3 MUM), while 4 hydroxy-7-(2'-deoxy-2'-fluoro-4'-azido-beta-D-ribofuranosyl)pyrrolo[2,3-d] pyrimidine 9 and 4-amino-5-fluoro-7-(2'-deoxy-2'-fluoro-4'-azido-beta-D ribofuranosyl)pyrrolo[2,3-d] pyrimidine 11 showed moderate activity (EC(50)=13+/ 8 and 5.4+/-0.3 MUM, respectively). The cytotoxicity of these compounds has also been assessed. No significant cytotoxicities were found for any of these compounds with concentrations up to 25 MUM. PMID- 21974952 TI - Synthesis and in vivo evaluation of cyclic diaminopropane BACE-1 inhibitors. AB - The synthesis, evaluation, and structure-activity relationships of a set of related constrained diaminopropane inhibitors of BACE-1 are described. The full in vivo profile of an optimized inhibitor in both normal and P-gp deficient mice is compared with data generated in normal rats. PMID- 21974953 TI - Functional characterization of rat glutaryl-CoA dehydrogenase and its comparison with straight-chain acyl-CoA dehydrogenase. AB - Glutaryl-CoA dehydrogenase catalyzes the oxidative decarboxylation of the gamma carboxylate of the substrate, glutaryl-CoA, to yield crotonyl-CoA and CO(2). The enzyme is a member of the acyl-CoA dehydrogenase (ACD) family of flavoproteins. In the present study, the catalytic properties of this enzyme, including its substrate specificity, isomerase activity, and interactions with inhibitors, were systematically studied. Our results indicated that the enzyme has its catalytic properties very similar to those of short-chain and medium-chain acyl-CoA dehydrogenase except its additional decarboxylation reaction. Therefore, the inhibitors of fatty acid oxidation targeting straight chain acyl-CoA dehydrogenase could also function as inhibitors for amino acid metabolism of lysine, hydroxylysine, and tryptophan. PMID- 21974954 TI - Acid mediated formation of an N-acyliminium ion from tubulysins: a new methodology for the synthesis of natural tubulysins and their analogs. AB - Tubuylsins are extremely potent cytotoxic agents which inhibit tubulin polymerization and lead to cell cycle arrest and apoptosis. Tubulysins have been isolated from fermentation mixtures and have been chemically synthesized; however, these efforts have been hampered by poor yields and arduous purifications. In contrast, treatment of a mixture of natural tubulysins A, B, C, G, and I, obtained from a fermentation batch with trifluoroacetic acid results in the formation of a single N-acyliminium ion. Subsequent addition of butyric, isopentyl, or acetic acid results in the formation of tubulysin B, A, or I, respectively, as a single species. New tubulysin analogs can be formed upon treatment of the acyliminium ion with other nucleophiles such as alcohols, thiols, and nitriles, resulting in corresponding N-acyl-N,O-acetals, N-acyl-N,S thioacetals, and N,N'-diacyl-aminals. Carbon-carbon bond formation is also possible with a modification of this protocol. The cytotoxicies of the natural tubulysins and tubulysin analogs synthesized by this method were evaluated on KB cells. PMID- 21974955 TI - Protein binding site analysis by means of structural interaction fingerprint patterns. AB - We introduce a new approach to the known concept of interaction profiles, based on Structural Interaction Fingerprints (SIFt), for precise and rapid binding site description. A set of scripts for batch generation and analysis of SIFt were prepared, and the implementation is computationally efficient and supports parallelization. It is based on a 9-digit binary interaction pattern that describes physical ligand-protein interactions in structures and models of ligand protein complexes. The tool performs analysis and identifies binding site residues (crucial and auxiliary) and classifies interactions according to type (hydrophobic, aromatic, charge, polar, side chain, and backbone). It is convenient and easy to use, and gives manageable output data for both, interpretation and further processing. In the presented Letter, SIFts are applied to analyze binding sites in models of antagonist-5-HT7 receptor complexes and structures of cyclin dependent kinase 2-ligand complexes. PMID- 21974956 TI - AHL-dependent quorum sensing inhibition: synthesis and biological evaluation of alpha-(N-alkyl-carboxamide)-gamma-butyrolactones and alpha-(N-alkyl-sulfonamide) gamma-butyrolactones. AB - New N-acylhomoserine lactone (AHL) analogues in which the amide function is replaced by a reverse-amide one have been studied as AHL QS modulators. The series of compounds consists of alpha-(N-alkyl-carboxamide)-gamma-butyrolactones, alpha-(N-alkyl-sulfonamide)-gamma-butyrolactones, and 2-(N-alkyl-carboxamide) cyclopentanones and cyclopentanols. Most active compounds exhibited antagonist activities against LuxR reaching the 30 MUM range. PMID- 21974957 TI - Identification of novel NK1/NK3 dual antagonists for the potential treatment of schizophrenia. AB - During the lead optimization of NK(1)/NK(3) receptor antagonists program, a focused exploration of molecules bearing a lactam moiety was performed. The aim of the investigation was to identify the optimal position of the carbonyl and hydroxy methyl group in the lactam moiety, in order to maximize the in vitro affinity and the level of insurmountable antagonism at both NK(1) and NK(3) receptors. The synthesis and biological evaluation of these novel lactam derivatives, with potent and balanced NK(1)/NK(3) activity, were reported in this paper. PMID- 21974958 TI - Anti-Pim-1 mAb inhibits activation and proliferation of T lymphocytes and prolongs mouse skin allograft survival. AB - Pim-1 is an important signaling molecule mediating cell proliferation and survival. Our previous study identified a Pim-1 specific monoclonal antibody, P9, with significant inhibitory effect on cell proliferation. Herein, we report that P9 inhibited the activation and proliferation of PHA-stimulated human PBMC and induced them to undergo apoptosis. In contrast, P9 showed little effect on freshly isolated human blood T lymphocytes which poorly expressed Pim-1. P9 also detected an up-regulation of Pim-1 in mouse lymphocytes after mitogen stimulation, and showed similar selective inhibition on stimulated cells as observed with hPBMC. Furthermore, P9 inhibited the in vitro mixed lymphocyte reaction and P9 treatment significantly prolonged the survival of mouse skin allografts (P<0.001). It is concluded that Pim-1 expression correlates with lymphocyte proliferation and activation. P9 functions as a Pim-1 antagonist and is potential for immunosuppressive therapy. PMID- 21974960 TI - Electrochemical behavior of monolayer and bilayer graphene. AB - Results of a study on the electrochemical properties of exfoliated single and multilayer graphene flakes are presented. Graphene flakes were deposited on silicon/silicon oxide wafers to enable fast and accurate characterization by optical microscopy and Raman spectroscopy. Conductive silver paint and silver wires were used to fabricate contacts; epoxy resin was employed as a masking coating in order to expose a stable, well-defined area of graphene. Both multilayer and monolayer graphene microelectrodes showed quasi-reversible behavior during voltammetric measurements in potassium ferricyanide. However, the standard heterogeneous charge transfer rate constant, k degrees , was estimated to be higher for monolayer graphene flakes. PMID- 21974959 TI - Incidence of seed migration to the chest, abdomen, and pelvis after transperineal interstitial prostate brachytherapy with loose (125)I seeds. AB - BACKGROUND: The aim was to determine the incidence of seed migration not only to the chest, but also to the abdomen and pelvis after transperineal interstitial prostate brachytherapy with loose (125)I seeds. METHODS: We reviewed the records of 267 patients who underwent prostate brachytherapy with loose (125)I seeds. After seed implantation, orthogonal chest radiographs, an abdominal radiograph, and a pelvic radiograph were undertaken routinely to document the occurrence and sites of seed migration. The incidence of seed migration to the chest, abdomen, and pelvis was calculated. All patients who had seed migration to the abdomen and pelvis subsequently underwent a computed tomography scan to identify the exact location of the migrated seeds. Postimplant dosimetric analysis was undertaken, and dosimetric results were compared between patients with and without seed migration. RESULTS: A total of 19,236 seeds were implanted in 267 patients. Overall, 91 of 19,236 (0.47%) seeds migrated in 66 of 267 (24.7%) patients. Sixty nine (0.36%) seeds migrated to the chest in 54 (20.2%) patients. Seven (0.036%) seeds migrated to the abdomen in six (2.2%) patients. Fifteen (0.078%) seeds migrated to the pelvis in 15 (5.6%) patients. Seed migration occurred predominantly within two weeks after seed implantation. None of the 66 patients had symptoms related to the migrated seeds. Postimplant prostate D90 was not significantly different between patients with and without seed migration. CONCLUSION: We showed the incidence of seed migration to the chest, abdomen and pelvis. Seed migration did not have a significant effect on postimplant prostate D90. PMID- 21974961 TI - The end of innocence: flowering networks explode in complexity. AB - Substantial recent advances in genome-scale transcription factor target mapping have provided a fresh view of the gene networks governing developmental transitions. In particular, our understanding of the fine-scale spatial and temporal dynamics underlying the floral transition at the shoot apex has seen great advances in the past two years. Single transcription factors are regularly observed to act in complex manners, directly promoting the expression of particular targets while directly repressing the expression of others, based at least partly on defined heterodimerization patterns. For single regulators this behavior reaches into distinct physiological processes, providing compelling evidence that particular transcription factors act to directly integrate diverse processes to orchestrate complex developmental transitions. PMID- 21974962 TI - Acute low back pain is marked by variability: An internet-based pilot study. AB - BACKGROUND: Pain variability in acute LBP has received limited study. The objectives of this pilot study were to characterize fluctuations in pain during acute LBP, to determine whether self-reported 'flares' of pain represent discrete periods of increased pain intensity, and to examine whether the frequency of flares was associated with back-related disability outcomes. METHODS: We conducted a cohort study of acute LBP patients utilizing frequent serial assessments and Internet-based data collection. Adults with acute LBP (lasting <=3 months) completed questionnaires at the time of seeking care, and at both 3 day and 1-week intervals, for 6 weeks. Back pain was measured using a numerical pain rating scale (NPRS), and disability was measured using the Oswestry Disability Index (ODI). A pain flare was defined as 'a period of increased pain lasting at least 2 hours, when your pain intensity is distinctly worse than it has been recently'. We used mixed-effects linear regression to model longitudinal changes in pain intensity, and multivariate linear regression to model associations between flare frequency and disability outcomes. RESULTS: 42 of 47 participants (89%) reported pain flares, and the average number of discrete flare periods per patient was 3.5 over 6 weeks of follow-up. More than half of flares were less than 4 hours in duration, and about 75% of flares were less than one day in duration. A model with a quadratic trend for time best characterized improvements in pain. Pain decreased rapidly during the first 14 days after seeking care, and leveled off after about 28 days. Patients who reported a pain flare experienced an almost 3-point greater current NPRS than those not reporting a flare (mean difference [SD] 2.70 [0.11]; p < 0.0001). Higher flare frequency was independently associated with a higher final ODI score (beta [SE} 0.28 (0.08); p = 0.002). CONCLUSIONS: Acute LBP is characterized by variability. Patients with acute LBP report multiple distinct flares of pain, which correspond to discrete increases in pain intensity. A higher flare frequency is associated with worse disability outcomes. PMID- 21974963 TI - Comparison of acute coronary syndrome in patients receiving versus not receiving chronic dialysis (from the Global Registry of Acute Coronary Events [GRACE] Registry). AB - Patients with end-stage renal disease commonly develop acute coronary syndromes (ACS). Little is known about the natural history of ACS in patients receiving dialysis. We evaluated the presentation, management, and outcomes of patients with ACS who were receiving dialysis before presentation for an ACS and were enrolled in the Global Registry of Acute Coronary Events (GRACE) at 123 hospitals in 14 countries from 1999 to 2007. Of 55,189 patients, 579 were required dialysis at presentation. Non-ST-segment elevation myocardial infarction was the most common ACS presentation in patients receiving dialysis, occurring in 50% (290 of 579) of patients versus 33% (17,955 of 54,610) of those not receiving dialysis. Patients receiving dialysis had greater in-hospital mortality rates (12% vs 4.8%; p <0.0001) and, among those who survived to discharge, greater 6-month mortality rates (13% vs 4.2%; p <0.0001), recurrent myocardial infarction (7.6% vs 2.9%; p <0.0001), and unplanned rehospitalization (31% vs 18%; p <0.0001). The outcome in patients receiving dialysis was worse than that predicted by their calculated GRACE risk score for in-hospital mortality (7.8% predicted vs 12% observed; p <0.05), 6-month mortality/myocardial infarction (10% predicted vs 21% observed; p <0.05). In conclusion, in the present large multinational study, approximately 1% of patients with ACS were receiving dialysis. They were more likely to present with non-ST-segment elevation myocardial infarction, and had markedly greater in hospital and 6-month mortality. The GRACE risk score underestimated the risk of major events in patients receiving dialysis. PMID- 21974964 TI - Shape-tailoring and catalytic function of anisotropic gold nanostructures. AB - We report a facile, one-pot, shape-selective synthesis of gold nanoparticles in high yield by the reaction of an aqueous potassium tetrachloroaurate(III) solution with a commercially available detergent. We prove that a commercial detergent can act as a reducing as well as stabilizing agent for the synthesis of differently shaped gold nanoparticles in an aqueous solution at an ambient condition. It is noteworthy that the gold nanoparticles with different shapes can be prepared by simply changing the reaction conditions. It is considered that a slow reduction of the gold ions along with shape-directed effects of the components of the detergent plays a vital function in the formation of the gold nanostructures. Further, the as-prepared gold nanoparticles showed the catalytic activity for the reduction reaction of 4-nitrophenol in the presence of sodium borohydride at room temperature. PMID- 21974965 TI - No evidence of Bartonella quintana but detection of Acinetobacter baumannii in head lice from elementary schoolchildren in Paris. AB - The human body louse is the only known vector of Bartonella quintana. However, the presence of this bacterium has recently been detected in the head lice of homeless individuals and Nepalese slum children. Previous studies have reported the isolation of Acinetobacter baumannii from the body lice of homeless individuals. An epidemiological survey including 74 schools was conducted between 2008 and 2009 in Paris. After a first visual examination, the hair of children with suspected pediculosis was combed with a fine-tooth comb to collect live adult head lice. Molecular studies were performed on randomly selected DNA samples to detect B. quintana and A. baumannii by specific quantitative real-time PCR. Among a collection of 288 DNA samples, B. quintana was not detected, but A. baumannii was detected in 95 DNA samples (33%). Further study is needed to determine the significance of the finding of A. baumannii in head lice. PMID- 21974966 TI - Granulomatous interstitial nephritis associated with disseminated histoplasmosis in an immunocompetent patient. AB - We present a case of a 64-year-old man with a prolonged history of fatigue, weight loss, fever, and kidney failure. Kidney biopsy showed severe granulomatous interstitial nephritis with numerous giant cells. Silver stains identified fungal micro-organisms consistent with Histoplasma species. Despite antifungal treatment, the patient died of overwhelming infection a few weeks later. This report emphasizes the importance of diagnosing histoplasmosis early. A high degree of suspicion is required to make the diagnosis of histoplasmosis in a case of granulomatous interstitial nephritis. PMID- 21974967 TI - New insights into human minimal change disease: lessons from animal models. AB - The pathogenesis of minimal change disease (MCD), considered to be the simplest form of nephrotic syndrome, has been one of the major unsolved mysteries in kidney disease. In this review, recent landmark studies that have led to the unraveling of MCD are discussed. A recent study now explains the molecular basis of major clinical and morphologic changes in MCD. Overproduction of angiopoietin like 4 (ANGPTL4) in podocytes in MCD causes binding of ANGPTL4 to the glomerular basement membrane, development of nephrotic-range selective proteinuria, diffuse effacement of foot processes, and loss of glomerular basement membrane charge, but is not associated with changes shown by light microscopy in the glomerular and tubulointerstitial compartments. At least some of this ability of ANGPTL4 to induce proteinuria is linked to a deficiency of sialic acid residues because oral supplementation with sialic acid precursor N-acetyl-d-mannosamine improves sialylation of podocyte-secreted ANGPTL4 and significantly decreases proteinuria. Animal models of MCD, recent advances in potential biomarkers, and studies of upstream factors that may initiate glomerular changes also are discussed. In summary, recent progress in understanding MCD is likely to influence the diagnosis and treatment of MCD in the near future. PMID- 21974968 TI - Microarray profiling reveals the integrated stress response is activated by halofuginone in mammary epithelial cells. AB - BACKGROUND: The small molecule Halofuginone (HF) is a potent regulator of extracellular matrix (ECM ) gene expression and is unique in its therapeutic potential. While the basis for HF effects is unknown, inhibition of TGFbeta signaling and activation of the amino acid restriction response (AAR) have been linked to HF transcriptional control of a number of ECM components and amelioration of fibrosis and alleviation of autoimmune disease by regulation of Th17 cell differentiation, respectively. The aim of this study was to generate a global expression profile of HF targets in epithelial cells to identify potential mediators of HF function in this cell type. RESULTS: We report that HF modulation of the expression of the ECM remodeling protein Mmp13 in epithelial cells is separable from previously reported effects of HF on TGFbeta signal inhibition, and use microarray expression analysis to correlate this with transcriptional responses characteristic of the Integrated Stress Response (ISR). CONCLUSIONS: Our findings suggest activation of the ISR may be a common mechanism underlying HF biological effects. PMID- 21974969 TI - Influence of catechol-o-methyltransferase genotype (Val158Met) on endocrine, sympathetic nervous and mucosal immune systems in breast cancer survivors. AB - Stress can play an important role in development of cancer-related fatigue (CRF) by activating the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic nervous system (SNS), and altering the immune system. This study examined the influence of catechol-O-methyltransferase (COMT) Val158Met genotypes on salivary markers of HPA axis (cortisol), SNS (alpha-amylase) and immune (IgA) systems, as well as on CRF in breast cancer survivors (BCS). One-hundred BCS participated. After amplifying Val158Met COMT polymorphisms by polymerase chain reaction, three COMT genotypes were considered: Val/Val, Val/Met, Met/Met. Salivary cortisol, alpha-amylase activity, salivary flow rate, and IgA concentration were collected from non-stimulated saliva. CRF was assessed with the fatigue subscale of the Profile of Mood State (POMS) questionnaire. We found that BCS carrying Met/Met genotype reported higher cortisol concentration, alpha-amylase activity and greater CRF than those with Val/Met (P < 0.05) and Val/Val (P < 0.001) genotypes. No differences in salivary flow rate or IgA concentration (P > 0.20) were found. The results suggest that BCS carrying Met/Met genotype exhibit greater dysfunction of the HPA axis and SNS system associated with severe CRF. This study is important because it strives to understand biological factors that predispose some BCS to higher levels of CRF. PMID- 21974971 TI - Pathogen associated molecular pattern motifs from Gram-positive and Gram-negative bacteria induce different inflammatory mediator profiles in equine blood. AB - Although the incidence of Gram-positive infection in horses is increasing, little is known about differences in inflammatory response between Gram-positive and Gram-negative organisms in this species. Equine blood was stimulated with components of both Gram-negative and Gram-positive organisms: lipopolysaccharide (LPS); lipoteichoic acid (LTA); peptidoglycan (PG); with combinations of LPS, LTA and PG; and with phosphate buffered saline (control). LPS, LTA and PG stimulated tumor necrosis factor (TNF) and interleukin (IL)-6 production but only LTA and PG stimulated IL-1beta production from whole blood. LPS was a more potent inducer of TNF than either LTA or PG and both LPS and LTA were more potent inducers of IL-6 than PG. Generally, combinations of pathogen associated molecular patterns (PAMPs) did not elicit greater inflammatory mediator responses when compared to LPS, LTA or PG alone, although there was some synergism between the effects of LPS and LTA. The repertoire of inflammatory mediators provoked by Gram-positive vs. Gram-negative motifs is thus distinctly different. As novel immunomodulatory therapies are developed for use in the horse, care should be exercised when applying treatments for endotoxemia to animals with Gram-positive infections given the different cytokine response profiles. PMID- 21974972 TI - Glycoprotein IIb-IIIa inhibitors. AB - Platelets play a pivotal role in the pathogenesis of coronary artery disease and myocardial infarction. Therefore, great interests have been focused in the last decades on improvement in antiplatelet therapies, that currently are regarded as main pillars in the prevention and treatment of coronary artery disease, with special attention to glycoprotein IIb-IIIa (GP IIb-IIIa) receptors, that mediates the final stage of platelet activation. GP IIb-IIIa inhibitors, especially abciximab, have been shown to improve clinical outcome in patients undergoing primary angioplasty for STEMI. Upstream administration cannot routinely recommended, but may potentially be considered among high-risk patients within the first 4 h from symptoms onset. In case of periprocedural administration of antithrombotic therapy, Bivalirudin should be considered, especially in patients at high risk for bleeding complications. Among high-risk patients with acute coronary syndromes, an early invasive strategy with selective downstream administration of GP IIb-IIIa inhibitors is the strategy of choice, whereas bivalirudin should be considered in patients at high risk for bleeding complications. Among patients with unstable angina GP IIb-IIIa inhibitors should be considered only in case of evidence of intracoronary thrombus or in case of thrombotic complications (as provisional use). Further, randomized trials are certainly needed in the era of new oral antiplatelet therapies, and with strategies to prevent bleeding complications such as larger use of radial approach, mechanical closure devices, bivalirudin, or postprocedural protamine administration to promote early sheat removal. PMID- 21974973 TI - Disease-modifying drug initiation patterns in commercially insured multiple sclerosis patients: a retrospective cohort study. AB - BACKGROUND: The goal of this research was to compare the demographics, clinical characteristics and treatment patterns for newly diagnosed multiple sclerosis (MS) patients in a commercial managed care population who received disease modifying drug (DMD) therapy versus those not receiving DMD therapy. METHODS: A retrospective cohort study using US administrative healthcare claims identified individuals newly diagnosed with MS (no prior MS diagnosis 12 months prior using ICD-9-CM 340) and >=18 years old during 2001-2007 to characterize them based on demographics, clinical characteristics, and pharmacologic therapy for one year prior to and a minimum of one year post-index. The index date was the first MS diagnosis occurring in the study period. Follow-up of subjects was done by ICD-9 CM code identification and not by actual chart review. Multivariate analyses were conducted to adjust for confounding variables. RESULTS: Patients were followed for an average of 35.7+/-17.5 months after their index diagnosis. Forty-three percent (n=4,462) of incident patients received treatment with at least one of the DMDs during the post-index period. Treated patients were primarily in the younger age categories of 18-44 years of age, with DMD therapy initiated an average of 5.3+/-9.1 months after the index diagnosis. Once treatment was initiated, 27.7% discontinued DMD therapy after an average of 17.6+/-14.6 months, and 16.5% had treatment gaps in excess of 60 days. CONCLUSIONS: Nearly 60% of newly-diagnosed MS patients in this commercial managed care population remained untreated while over a quarter of treated patients stopped therapy and one-sixth experienced treatment gaps despite the risk of disease progression or a return of pre-treatment disease activity. PMID- 21974974 TI - Contribution of thin slice (1 mm) oblique coronal proton density-weighted MR images for assessment of anteromedial and posterolateral bundle damage in anterior cruciate ligament injuries. AB - PURPOSE: To evaluate the diagnostic efficacy of using additional oblique coronal 1 mm proton density-weighted (PDW) MR imaging of the knee for detection and grading anterior cruciate ligament (ACL), anteromedial bundle (AMB) and posterolateral bundle (PLB) injuries. MATERIALS AND METHODS: We prospectively assessed preoperative MR images of 50 patients (36 men, 14 women; age range, 18 62 years). First, we compared the diagnostic performance of routine sagittal (3 mm) and additional oblique coronal images (1 mm) for ACL tears. Then, we compared the tear types (AMB or PLB) and grade presumed from oblique coronal MR imaging with arthroscopy. RESULTS: Arthroscopy revealed ACL tear in 24 (48%) patients. There was significant difference between sagittal images and arthroscopy results for ACL tear recognition (p<0.001). No significant difference was detected for oblique coronal images when compared with arthroscopy results (p=0.180). Sensitivity and specificity values for ACL tear diagnosis were 37.04% and 95.65% for sagittal images; 74.07% and 91.30% for oblique coronal images. There was no significant difference between arthroscopy and oblique coronal MR images in grading AMB and PLB injuries (p>0.05). CONCLUSION: Addition of thin slice oblique coronal images to conventional sequences could better contribute to better verifying the presence of ACL tear and in determining its grade. PMID- 21974975 TI - Social deprivation stress is a triggering factor for the emergence of anxiety- and depression-like behaviours and leads to reduced brain BDNF levels in C57BL/6J mice. AB - Stress is a main risk factor that can trigger psychiatric disorders, including anxiety and major depression. Neurotrophins, such as Brain-Derived Neurotrophic Factor (BDNF), have been identified as neuroendocrine effectors involved in the response to stress and in the neurobehavioural changes associated with depression. Aim of this paper was to study the relationship between neuroendocrine activation (circulating corticosterone and brain BDNF levels) and a wide array of depression- and anxiety-like behaviours (anhedonia, behavioural despair, generalised and social anxiety) resulting from exposure to chronic stress. To this end, 3-month-old C57BL/6J male mice were exposed to either chronic disruption of the social structure (SS), to a stable social structure (SG) or to social deprivation (SD), a condition lacking social stimuli. Results show that, despite not developing anhedonia (decreased preference for a sucrose solution), SD mice were characterised by increased emotionality and hypothalamic pituitary-adrenal axis reactivity in addition to reduced BDNF levels. By contrast, SG and SS mice showed increased anhedonia accompanied by no alterations in the behavioural and neuroendocrine profile. The results here reported indicate that mice exposed to different social housing conditions use different behavioural strategies to cope with external challenges. In addition they suggest that social deprivation might represent a stressful condition triggering the emergence of both anxiety- and depression-like behaviours and clearly indicate BDNF as a main neurobiological variable mediating these responses. PMID- 21974976 TI - Hair cortisol as a biological marker of chronic stress: current status, future directions and unanswered questions. AB - The detrimental effects of stress on human health are being increasingly recognized. There is a critical need for the establishment of a biomarker that accurately measures its intensity and course over time. Such a biomarker would allow monitoring of stress, increase understanding of its pathophysiology and may help identify appropriate and successful management strategies. Whereas saliva and urine cortisol capture real-time levels, hair cortisol analysis presents a complementary means of monitoring stress, capturing systemic cortisol exposure over longer periods of time. This novel approach for cortisol quantification is being increasingly used to identify the effects of stress in a variety of pathological situations, from chronic pain to acute myocardial infarctions. Because of its ability to provide a long-term, month-by-month measure of systemic cortisol exposure, hair cortisol analysis is becoming a useful tool, capable of answering clinical questions that could previously not be answered by other tests. In this paper we review the development, current status, limitations and outstanding questions regarding the use of hair cortisol as a biomarker of chronic stress. PMID- 21974977 TI - Ovarian morphology in premenstrual dysphoria. AB - Ovarian cyclicity is a prerequisite for premenstrual dysphoria (PMD), as illustrated by the fact that this condition is effectively eliminated by ovariectomy or by treatment with a GnRH agonist. Despite the possibility of differences in ovarian function between women with and without PMD, no study comparing ovarian morphology in these two groups has ever been published. Fifty two women were recruited for this study; 26 had premenstrual dysphoria, fulfilling criteria slightly modified from those of the premenstrual dysphoric disorder, and 26 were asymptomatic age-matched controls. Ovarian morphology was assessed using transvaginal 7 MHz ultrasonography on day 5 after the start of menses, and venous blood was sampled for hormone analysis on days 3 and 8, the expected day of ovulation, and day -4 of the menstrual cycle. There were no significant differences between the groups with respect to the prevalence of polycystic ovaries (PCO), the total number of follicles, the total ovarian volume or serum levels of androgen hormones. In addition, serum free testosterone levels in late premenstrual phase showed an inverse association to premenstrual symptoms of irritability and a similar inverse association trend to symptoms of depressed mood. Unexpectedly, the prevalence of ovaries with fewer than five antral or growing follicles was significantly higher in women with PMD than in controls (p=0.016). While the results do not support a role for PCO or androgen hormones in eliciting late luteal phase irritability, the possible relationship between oligofollicular ovaries and PMD deserves further study. PMID- 21974978 TI - Cavernostomy x resection for pulmonary aspergilloma: a 32-year history. AB - BACKGROUND: The most adequate surgical technique for the treatment of pulmonary aspergilloma is still controversial. This study compared two groups of patients submitted to cavernostomy and pulmonary parenchyma resection. METHODS: Cases of pulmonary aspergilloma operated upon between 1979 and 2010 were analyzed retrospectively. Group 1 consisted of patients submitted to cavernostomy and group 2 of patients submitted to pulmonary parenchyma resection. The following variables were compared between groups: gender, age, number of hospitalizations, pre- and postoperative length of hospital stay, time of follow-up, location and type of aspergilloma, preoperative symptoms, underlying disease, type of fungus, preoperative pulmonary function, postoperative complications, patient progression, and associated diseases. RESULTS: A total of 208 patients with pulmonary aspergilloma were studied (111 in group 1 and 97 in group 2). Group 1 was older than group 2. The number of hospitalizations, length of hospital stay and time of follow-up were higher in group 1. Hemoptysis was the most frequent preoperative symptom in group 1. Preoperative respiratory malfunction was more severe in group 1. Hemorrhagic complications and recurrence were more frequent in group 1 and infectious complications and residual pleural space were more common in group 2. Postoperative dyspnea was more frequent in group 2. Patient progression was similar in the two groups. No difference in the other factors was observed between groups. CONCLUSIONS: Older patients with severe preoperative respiratory malfunction and peripheral pulmonary aspergilloma should be submitted to cavernostomy. The remaining patients can be treated by pulmonary resection. PMID- 21974979 TI - Reduction of nectarine decay caused by Rhizopus stolonifer, Botrytis cinerea and Penicillium digitatum with Aloe vera gel alone or with the addition of thymol. AB - Two nectarine cultivars ('Flavela' and 'Flanoba') were treated with Aloe vera gel alone, or with the addition of thymol, and then inoculated with Rhizopus stolonifer, Botrytis cinerea and Penicillium digitatum. Both treatments were effective in reducing the decay incidence caused by the 3 fungi species, although the addition of thymol did not generally improve the efficacy of Aloe vera gel on reducing the infection damage. The coatings were clearly effective in reducing the postharvest ripening process of both nectarine cultivars manifested by a delay in ethylene production and respiration rate, weight loss and softening. Interestingly, these coatings showed effectiveness on reducing decay development in inoculated fruits and thus Aloe vera could be considered as natural antifungal compound and might serve as alternative of synthetic fungicides. PMID- 21974980 TI - Detection of Helicobacter pylori in raw bovine milk by fluorescence in situ hybridization (FISH). AB - The transmission pathways of Helicobacter pylori in humans have not been fully elucidated. Research in the last decade has proposed that foodborne transmission, among others, may be a plausible route of human infection. Owing to the organism's fastidious growth characteristics and its ability to convert to viable, yet unculturable states upon exposure to stress conditions, the detection of H. pylori in foods via culture-dependent methods has been proven to be laborious, difficult and in most cases unsuccessful. Hence, nucleic acid-based methods have been proposed as alternative methods but, to date, only PCR-based methods have been reported in the literature. In the current study, fluorescence in situ hybridization (FISH) was used for the detection of H. pylori in raw, bulk tank bovine milk. After repeated milk centrifugation and washing steps, the bacterial flora of raw milk was subjected to fixation and permeabilization and H. pylori detection was conducted by FISH after hybridization with an H. pylori specific 16S rRNA-directed fluorescent oligonucleotide probe. Using this protocol, H. pylori was detected in four out of the twenty (20%) raw milk samples examined. The data presented in this manuscript indicate that FISH can serve as an alternative molecular method for screening raw bovine milk for the presence of H. pylori. PMID- 21974981 TI - The grape must non-Saccharomyces microbial community: impact on volatile thiol release. AB - Several studies have reported the beneficial influence of non-Saccharomyces yeasts and their potential applications in the wine industry, mainly in mixed culture fermentation with S. cerevisiae. The potential impact of 15 non Saccharomyces strains from 7 species on 4-methyl-4-sulfanylpentan-2-one (4MSP) and 3-sulfanylhexan-1-ol (3SH) release in model medium and Sauvignon Blanc must was evaluated after partial fermentation. Whereas the impact of non-Saccharomyces on 4MSP release in both media was low, some M. pulcherrima, T. delbrueckii and K. thermotolerans strains had a high capacity to release 3SH, despite their minimal fermentation activity. As previously demonstrated for Saccharomyces yeast, this contribution is strain dependant. Taking into account their dynamic and quantitative presence during the whole process, the real impact of non Saccharomyces yeast on 4MSP and 3SH release was evaluated using a recreated community simulating the yeast ecosystem. Our results revealed a positive impact on 3SH release in Sauvignon Blanc wines by promoting non-Saccharomyces yeast activity and delaying the growth of S. cerevisiae. Some non-Saccharomyces yeast strains are capable of making a positive contribution to volatile thiol release in wines, essentially during the pre-fermentation stage in winemaking, when this microbiological sub-population is dominant. PMID- 21974982 TI - [Research in surgery: an easy road?]. PMID- 21974984 TI - Thermoelectric properties of Ca0.8Dy0.2MnO3 synthesized by solution combustion process. AB - High-quality Ca0.8Dy0.2MnO3 nano-powders were synthesized by the solution combustion process. The size of the synthesized Ca0.8Dy0.2MnO3 powders was approximately 23 nm. The green pellets were sintered at 1150-1300 degrees C at a step size of 50 degrees C. Sintered Ca0.8Dy0.2MnO3 bodies crystallized in the perovskite structure with an orthorhombic symmetry. The sintering temperature did not affect the Seebeck coefficient, but significantly affected the electrical conductivity. The electrical conductivity of Ca0.8Dy0.2MnO3 increased with increasing temperature, indicating a semiconducting behavior. The absolute value of the Seebeck coefficient gradually increased with an increase in temperature. The highest power factor (3.7 * 10-5 Wm-1 K-2 at 800 degrees C) was obtained for Ca0.8Dy0.2MnO3 sintered at 1,250 degrees C. In this study, we investigated the microstructure and thermoelectric properties of Ca0.8Dy0.2MnO3, depending on sintering temperature. PMID- 21974983 TI - rTMS combined with task-oriented training to improve symmetry of interhemispheric corticomotor excitability and gait performance after stroke: a randomized trial. AB - BACKGROUND: The model of interhemispheric competition after stroke has been established for the upper but not for the lower extremity. Repetitive transcranial magnetic stimulation (rTMS) of the brain has been shown to modulate cortical excitability. OBJECTIVE: The purpose of this study was to investigate the effects of rTMS followed by task-oriented training on cortical excitability and walking performance in individuals with chronic stroke. METHODS: A total of 24 patients with average Fugl-Meyer lower limb scores of 17.88 +/- 5.27 and average walking speeds of 63.81 +/- 18.25 cm/s were randomized into an experimental group and a control group. Participants received rTMS (experimental group) or sham rTMS (control group) followed by task-oriented training (30 minutes) for 10 sessions over 2 weeks. Repetitive TMS was applied at a 1-Hz frequency over the leg area of the motor cortex of the unaffected hemisphere for 10 minutes. Outcomes, including motor-evoked potential (MEP), lower-extremity Fugl-Meyer score, and gait performance, were measured before and after training. RESULTS: Decreased interhemispheric asymmetry of the amplitude of the MEP was noted after rTMS and task-oriented training. Improvement in spatial asymmetry of gait was comparable with increased symmetry in interhemispheric excitability. Motor control and walking ability were also significantly improved after rTMS and task-oriented training. CONCLUSIONS: rTMS enhances the effect of task-oriented training in those with chronic stroke, especially by increasing gait spatial symmetry and corticomotor excitability symmetry. PMID- 21974985 TI - Attitudes among medical and law students toward decision-making in regard to involuntary psychiatric hospitalization. AB - BACKGROUND: The management of individuals with mental illnesses sometimes requires involuntary hospitalization. The Israel Mental Health Act requires that cases of involuntary psychiatric hospitalization (IPH) be periodically reviewed by the district psychiatric committee. The discussion in the committee often leads to debate regarding the need for an IPH potentially depriving the patient of his freedom. Little is known about the way in which the psychiatrists and attorneys on these committees arrive at their decisions. The present study was designed to examine the views of future doctors and attorneys concerning cases of possible IPH to determine whether their decisions would be influenced by their respective professional educational backgrounds. METHODS: After compiling demographic data, we asked 170 students from each of the two disciplines what their decision would be in two hypothetical cases that dealt with the question of a prolongation of a psychiatric hospitalization. Questionnaires examining social distance and possible stigmatizing views concerning psychiatric patients were also distributed and collected. RESULTS: The response rates for the medical and law students were, respectively, 90% and 85%. We found no differences between the medical and law students regarding their views on prolongation of a psychiatric hospitalization. This was consistent regardless of whether the hospitalization was against the patient's will or according to his wish and against the treating physicians' advice. We also found that the medical and law students had similar general views regarding psychiatric patients, but that the latter evidenced greater social distance than the former. CONCLUSIONS: Academic background and socialization were not found to influence the decisions of students regarding IPH. Educational programs and exposure to psychiatric patients during law studies are proposed to lessen psychiatric stigma and promote better understanding between members of the two disciplines. PMID- 21974987 TI - Back to basics: Understanding the terminology associated with light- and energy based technology. PMID- 21974988 TI - Amniotic fluid inflammatory score is associated with pregnancy outcome in patients with mid trimester short cervix. AB - OBJECTIVE: We propose a novel amniotic fluid inflammatory score from a comprehensive cytokine analysis of patients with mid-trimester short cervix. STUDY DESIGN: Amniotic fluid from singleton gestations (n = 44) with a cervical length of <=25 mm between 16-24 weeks was assayed for 25 inflammatory mediators. Patient data were stratified according to gestational age at delivery (<34 vs >=34 weeks). Mediators that reached statistical significance were included in the amniotic fluid inflammatory score. Patients were assigned 1 point for each significant mediator if their level was in the upper quartile. The amniotic fluid inflammatory score was determined, and its relationship to other clinical characteristics was examined. RESULTS: Fourteen mediators met the criteria. A score of >=8 was predictive of delivery at <34 weeks' gestation (sensitivity, 87.0%; specificity, 100%; positive predictive value, 100%; negative predictive value, 87.5%). Twenty patients had a high inflammatory score (>=8); 24 patients had a low score. All patients with a high inflammatory score delivered at <30 weeks' gestation. CONCLUSION: The amniotic fluid inflammatory score is related to delivery outcome and clinical characteristics. PMID- 21974986 TI - Design and development of a peptide-based adiponectin receptor agonist for cancer treatment. AB - BACKGROUND: Adiponectin, a fat tissue-derived adipokine, exhibits beneficial effects against insulin resistance, cardiovascular disease, inflammatory conditions, and cancer. Circulating adiponectin levels are decreased in obese individuals, and this feature correlates with increased risk of developing several metabolic, immunological and neoplastic diseases. Thus, pharmacological replacement of adiponectin might prove clinically beneficial, especially for the obese patient population. At present, adiponectin-based therapeutics are not available, partly due to yet unclear structure/function relationships of the cytokine and difficulties in converting the full size adiponectin protein into a viable drug. RESULTS: We aimed to generate adiponectin-based short peptide that can mimic adiponectin action and be suitable for preclinical and clinical development as a cancer therapeutic. Using a panel of 66 overlapping 10 amino acid-long peptides covering the entire adiponectin globular domain (residues 105 254), we identified the 149-166 region as the adiponectin active site. Three dimensional modeling of the active site and functional screening of additional 330 peptide analogs covering this region resulted in the development of a lead peptidomimetic, ADP 355 (H-DAsn-Ile-Pro-Nva-Leu-Tyr-DSer-Phe-Ala-DSer-NH2). In several adiponectin receptor-positive cancer cell lines, ADP 355 restricted proliferation in a dose-dependent manner at 100 nM-10 MUM concentrations (exceeding the effects of 50 ng/mL globular adiponectin). Furthermore, ADP 355 modulated several key signaling pathways (AMPK, Akt, STAT3, ERK1/2) in an adiponectin-like manner. siRNA knockdown experiments suggested that ADP 355 effects can be transmitted through both adiponectin receptors, with a greater contribution of AdipoR1. In vivo, intraperitoneal administration of 1 mg/kg/day ADP 355 for 28 days suppressed the growth of orthotopic human breast cancer xenografts by ~31%. The peptide displayed excellent stability (at least 30 min) in mouse blood or serum and did not induce gross toxic effects at 5-50 mg/kg bolus doses in normal CBA/J mice. CONCLUSIONS: ADP 355 is a first-in-class adiponectin receptor agonist. Its biological activity, superior stability in biological fluids as well as acceptable toxicity profile indicate that the peptidomimetic represents a true lead compound for pharmaceutical development to replace low adiponectin levels in cancer and other malignancies. PMID- 21974989 TI - Vaginal cuff dehiscence: risk factors and management. AB - Vaginal cuff dehiscence and evisceration are rare but serious complications of pelvic surgery, specifically hysterectomy. The data on risks of vaginal cuff dehiscence are variable, and there is no consensus on how to manage this complication. In our review, we present a summary of the risk factors, with symptoms, precipitating events, and treatment options for patients with vaginal cuff dehiscence after pelvic surgery. In addition, we provide a review of the current literature on this important surgical outcome and suggestions for future research on the incidence and prevention of vaginal cuff dehiscence. PMID- 21974990 TI - Placental mesenchymal dysplasia. AB - Placental mesenchymal dysplasia is a benign condition that can be confused with a molar pregnancy by ultrasound scanning and gross examination. Conservative management should be considered with a normal-appearing singleton fetus and a cystic-appearing placenta. We present a case of placental mesenchymal dysplasia with a favorable outcome. PMID- 21974991 TI - Safer conception options for HIV-serodiscordant couples. PMID- 21974992 TI - One-year objective and functional outcomes of a randomized clinical trial of vaginal mesh for prolapse. AB - OBJECTIVE: The purpose of this study was to show 12-month outcomes of a randomized trial that compared vaginal prolapse repair with and without mesh. STUDY DESIGN: Women with stage >=2 prolapse were assigned randomly to vaginal repair with or without mesh. The primary outcome was prolapse stage <=1 at 12 months. Secondary outcomes included quality of life and complications. RESULTS: All 65 evaluable participants were followed for 12 months after trial stoppage for mesh exposures. Thirty-two women had mesh repair; 33 women had traditional repair. At 12 months, both groups had improvement of pelvic organ prolapse quantification test points to similar recurrence rates. The quality of life improved and did not differ between groups: 96.2% mesh vs 90.9% no-mesh subjects reported a cure of bulge symptoms; 15.6% had mesh exposures, and reoperation rates were higher with mesh. CONCLUSION: Objective and subjective improvement is seen after vaginal prolapse repair with or without mesh. However, mesh resulted in a higher reoperation rate and did not improve 1-year cure. PMID- 21974993 TI - Contrasting patterns of evolution following whole genome versus tandem duplication events in Populus. AB - Comparative analysis of multiple angiosperm genomes has implicated gene duplication in the expansion and diversification of many gene families. However, empirical data and theory suggest that whole-genome and small-scale duplication events differ with respect to the types of genes preserved as duplicate pairs. We compared gene duplicates resulting from a recent whole genome duplication to a set of tandemly duplicated genes in the model forest tree Populus trichocarpa. We used a combination of microarray expression analyses of a diverse set of tissues and functional annotation to assess factors related to the preservation of duplicate genes of both types. Whole genome duplicates are 700 bp longer and are expressed in 20% more tissues than tandem duplicates. Furthermore, certain functional categories are over-represented in each class of duplicates. In particular, disease resistance genes and receptor-like kinases commonly occur in tandem but are significantly under-retained following whole genome duplication, while whole genome duplicate pairs are enriched for members of signal transduction cascades and transcription factors. The shape of the distribution of expression divergence for duplicated pairs suggests that nearly half of the whole genome duplicates have diverged in expression by a random degeneration process. The remaining pairs have more conserved gene expression than expected by chance, consistent with a role for selection under the constraints of gene balance. We hypothesize that duplicate gene preservation in Populus is driven by a combination of subfunctionalization of duplicate pairs and purifying selection favoring retention of genes encoding proteins with large numbers of interactions. PMID- 21974994 TI - Changes in exon-intron structure during vertebrate evolution affect the splicing pattern of exons. AB - Exon-intron architecture is one of the major features directing the splicing machinery to the short exons that are located within long flanking introns. However, the evolutionary dynamics of exon-intron architecture and its impact on splicing is largely unknown. Using a comparative genomic approach, we analyzed 17 vertebrate genomes and reconstructed the ancestral motifs of both 3' and 5' splice sites, as also the ancestral length of exons and introns. Our analyses suggest that vertebrate introns increased in length from the shortest ancestral introns to the longest primate introns. An evolutionary analysis of splice sites revealed that weak splice sites act as a restrictive force keeping introns short. In contrast, strong splice sites allow recognition of exons flanked by long introns. Reconstruction of the ancestral state suggests these phenomena were not prevalent in the vertebrate ancestor, but appeared during vertebrate evolution. By calculating evolutionary rate shifts in exons, we identified cis-acting regulatory sequences that became fixed during the transition from early vertebrates to mammals. Experimental validations performed on a selection of these hexamers confirmed their regulatory function. We additionally revealed many features of exons that can discriminate alternative from constitutive exons. These features were integrated into a machine-learning approach to predict whether an exon is alternative. Our algorithm obtains very high predictive power (AUC of 0.91), and using these predictions we have identified and successfully validated novel alternatively spliced exons. Overall, we provide novel insights regarding the evolutionary constraints acting upon exons and their recognition by the splicing machinery. PMID- 21974995 TI - Response to 2009 pandemic and seasonal influenza vaccines co-administered to HIV infected and HIV-uninfected former drug users living in a rehabilitation community in Italy. AB - BACKGROUND: 2009 A(H1N1) pandemic influenza vaccination was recommended as a priority to essential workers and high-risk individuals, including HIV-infected patients and people living in communities. METHODS: HIV-infected and HIV uninfected former drug-users (18-60 years old) living in a rehabilitation community (San Patrignano, Italy) received one dose of a MF59-adjuvanted 2009 pandemic influenza vaccine and one dose of a 2009-2010 seasonal trivalent inactivated influenza vaccine (containing A/Brisbane/59/2007(H1N1), A/Brisbane/10/2007(H3N2), B/Brisbane/60/2008) simultaneously. Antibodies against each vaccine antigen were determined at the time of vaccination and one and six months post-vaccination by hemagglutination-inhibition test. RESULTS: 49 HIV infected and 60 HIV-uninfected subjects completed the study. Most (98%) HIV infected participants were on antiretroviral treatment, the median CD4+ cell count was 350 (IQR 300)cells/MUl and viremia was suppressed in 91.8% of cases. One month post-vaccination, no significant changes in immune-virological parameters were observed. One month post-vaccination, the immune responses to both pandemic and seasonal vaccine met the EMA-CPMP criteria for immunogenicity of influenza vaccines in both HIV-infected and HIV-uninfected subjects. No difference in vaccine responses was observed between the two groups. Six months after vaccination, the percentages of vaccinees with antibody titres >=1:40 and antibody geometric mean titres significantly decreased in both groups. However, they were significantly lower in HIV-infected than in HIV-uninfected vaccinees. In subjects who had been primed to seasonal influenza the year before (through either vaccination or natural infection), levels of antibodies against 2009 A(H1N1) were higher than those measured in unprimed subjects, both one month and six months post-vaccination. CONCLUSIONS: The co-administration of a single dose of 2009 pandemic MF59-adjuvanted influenza vaccine with a seasonal vaccine provided a protective immune response in both HIV-infected and HIV-uninfected individuals. Subjects who had been primed to seasonal influenza in the year preceding the pandemic had a more vigorous and long-lasting antibody response to 2009 pandemic vaccine. PMID- 21974996 TI - Band-selective chemical exchange saturation transfer imaging with hyperpolarized xenon-based molecular sensors. AB - Molecular imaging based on saturation transfer in exchanging systems is a tool for amplified and chemically specific magnetic resonance imaging. Xenon-based molecular sensors are a promising category of molecular imaging agents in which chemical exchange of dissolved xenon between its bulk and agent-bound phases has been use to achieve sub-picomolar detection sensitivity. Control over the saturation transfer dynamics, particularly when multiple exchanging resonances are present in the spectra, requires saturation fields of limited bandwidth and is generally accomplished by continuous wave irradiation. We demonstrate instead how band-selective saturation sequences based on multiple pulse inversion elements can yield saturation bandwidth tuneable over a wide range, while depositing less RF power in the sample. We show how these sequences can be used in imaging experiments that require spatial-spectral and multispectral saturation. The results should be applicable to all CEST experiments and, in particular, will provide the spectroscopic control required for applications of arrays of xenon chemical sensors in microfluidic chemical analysis devices. PMID- 21974997 TI - Robust slice-selective broadband refocusing pulses. AB - Slice-selective broadband refocusing pulses are of great interest in localized MR spectroscopy for improving spatial selectivity, reducing chemical-shift displacement errors, and reducing anomalous J modulation. In practice the bandwidth of RF pulses is limited by the maximum available B1 amplitude. The goal of the present work is to design slice-selective and broadband refocusing pulses which are tolerant against B1 deviations. Pulse design is performed by numerical optimization based on optimal control theory. A comprehensive study of different cost functions and their effect on the optimization is given. The optimized slice selective broadband refocusing pulses are compared to conventional Shinnar-Le Roux (SLR), broadband SLR, and hyperbolic secant pulses. In simulations and experiments optimized pulses were shown to fulfill broadband slice specifications over a range of +/-20% B1 scalings. Experimental validation showed a reduction of chemical-shift displacement error by a factor of 3 compared to conventional SLR pulses. PMID- 21974998 TI - Transfer of hyperpolarization from long T1 storage nuclei to short T1 neighbors using FLOPSY-8. AB - Nuclei with long T1s are optimal targets for dynamic nuclear polarization (DNP). Therefore, most of the agents used in metabolic imaging and spectroscopy studies are based on carboxylic acid moieties that lack protons, a strong source of dipolar relaxation. Metabolic flux information encoded into spectra of small molecule metabolites in the form of the 13C isotopomer data cannot be accessed using standard 13C hyperpolarization methods because protonated carbons relax too quickly through T1 dipolar relaxation. It is shown here that the longitudinal mixing sequence FLOPSY-8 can be used to transfer polarization from a long T1 storage nucleus to adjacent protonated carbons so that they may be detected with high sensitivity. We demonstrate that FLOPSY-8 allows a direct readout of isotopomer populations in butyrate and glutamate in vitro. PMID- 21974999 TI - Theory of mirrored time domain sampling for NMR spectroscopy. AB - A generalized theory is presented for novel mirrored hypercomplex time domain sampling (MHS) of NMR spectra. It is the salient new feature of MHS that two interferograms are acquired with different directionality of time evolution, that is, one is sampled forward from time t=0 to the maximal evolution time tmax, while the second is sampled backward from t=0 to -tmax. The sampling can be accomplished in a (semi) constant time or non constant-time manner. Subsequently, the two interferograms are linearly combined to yield a complex time domain signal. The manifold of MHS schemes considered here is defined by arbitrary settings of sampling phases ('primary phase shifts') and amplitudes of the two interferograms. It is shown that, for any two given primary phase shifts, the addition theorems of trigonometric functions yield the unique linear combination required to form the complex signal. In the framework of clean absorption mode (CAM) acquisition of NMR spectra being devoid of residual dispersive signal components, 'secondary phase shifts' represent time domain phase errors which are to be eliminated. In contrast, such secondary phase shifts may be introduced by experimental design in order to encode additional NMR parameters, a new class of NMR experiments proposed here. For generalization, it is further considered that secondary phase shifts may depend on primary phase shifts and/or sampling directionality. In order to compare with MHS theory, a correspondingly generalized theory is derived for widely used hypercomplex ('States') sampling (HS). With generalized theory it is shown, first, that previously introduced 'canonical' schemes, characterized by primary phases being multiples of pi/4, afford maximal intensity of the desired absorptive signals in the absence of secondary phase shifts, and second, how primary phases can be adjusted to maximize the signal intensity provided that the secondary phase shifts are known. Third, it is demonstrated that theory enables one to accurately measure secondary phase shifts and amplitude imbalances. Application to constant time 2D [13C, 1H] HSQC spectra recorded for a protein sample with canonical MHS/HS schemes showed that accurate CAM data acquisition can be readily implemented on modern spectrometers for experiments based on through-bond polarization transfer. Fourth, when moderate variations of secondary phase shifts with primary phase shift and/or sampling directionality are encountered, generalized theory allowed comparison of the robustness of different MHS/HS schemes for CAM data acquisition, and thus to identify the scheme best suited to suppress dispersive peak components and quadrature image peaks. Moreover, it is shown that for spectra acquired with several indirect evolution periods, the best suited scheme can be identified independently for each of the periods. PMID- 21975000 TI - Occurrence, fate and removal of synthetic oral contraceptives (SOCs) in the natural environment: a review. AB - Synthetic oral contraceptives (SOCs) are a group of compounds with progestagenic and/or androgenic activities, with some also possessing estrogenic activities. Recent research has documented that some of these emerging contaminants have adverse effects on aquatic organisms at very low concentrations. To facilitate the evaluation of their latent risks, published works on their occurrence and fate in the environment are reviewed. Androgenic/progestagenic relative potencies or relative binding affinity of these SOCs as well as their physicochemical properties and toxicity are summarized. Appropriate analytical methods are outlined for various environmental sample types, including methods of sample preparation and limit of detection/quantification (LOD/LOQ). Finally results on their occurrence and fate in wastewater treatment plants (WWTPs) and other environments are critically examined. PMID- 21975001 TI - Cyanobacterial blooms: statistical models describing risk factors for national scale lake assessment and lake management. AB - Cyanobacterial toxins constitute one of the most high risk categories of waterborne toxic biological substances. For this reason there is a clear need to know which freshwater environments are most susceptible to the development of large populations of cyanobacteria. Phytoplankton data from 134 UK lakes were used to develop a series of Generalised Additive Models and Generalised Additive Mixed Models to describe which kinds of lakes may be susceptible to cyanobacterial blooms using widely available explanatory variables. Models were developed for log cyanobacterial biovolume. Water colour and alkalinity are significant explanatory variables and retention time and TP borderline significant (R2-adj=21.9%). Surprisingly, the models developed reveal that nutrient concentrations are not the primary explanatory variable; water colour and alkalinity were more important. However, given suitable environments (low colour, neutral-alkaline waters), cyanobacteria do increase with both increasing retention time and increasing TP concentrations, supporting the observations that cyanobacteria are one of the most visible symptoms of eutrophication, particularly in warm, dry summers. The models can contribute to the assessment of risks to public health, at a regional to national level, helping target lake monitoring and management more cost-effectively at those lakes at the highest risk of breaching World Health Organisation guideline levels for cyanobacteria in recreational waters. The models also inform restoration options available for reducing cyanobacterial blooms, indicating that, in the highest risk lakes (alkaline, low colour lakes), risks can generally be lessened through management aimed at reducing nutrient loads and increasing flushing during summer. PMID- 21975002 TI - Relationship between the presence of newborn and the house dust endotoxin. AB - BACKGROUND: Exposure to house dust endotoxin induces of airways' inflammation. Endotoxin are produced by the Gram-negative bacteria, which are released into the stools and could contaminate domestic environment. OBJECTIVE: The newborn could contaminate his mattress by endotoxin. METHODS: The dusts of mattress and carpets of 97 newborn' dwellings were sampled at birth and after six months of life. Samplings were made in the bedroom from the baby and in the second place where the baby spent the longer time. The endotoxin concentration was measured by a quantitative Limulus assay and the bacterial contamination was evaluated using 3 selective agar media. RESULTS: Endotoxin concentration at birth was positively associated with the presence of both sibling and the number of inhabitants (p<0.01). At 6 months of life, the endotoxin concentration raised significantly not only in the mattresses (from a median of 17.6 (ranges: 0.4-346.7) to 79.6 (3.8-518.8) EU/mg) (p<0.0001), but also in the dust from the second place where the baby is sleeping (from 20.4 (0.8-226.3) to 101.8 (6.5-634.3) EU/mg) (p<0.001). Importantly, there was no change in endotoxin concentration from the carpets dust, and the environmental dwelling characteristics remained unchanged. The total bacterial contamination was also positively associated with endotoxin concentration in newborn mattress at birth (p<0.01) and showed a significant increase at 6 months of life of the newborn (p<0.01). CONCLUSION: The newborn is a significant source of house dust's endotoxin. PMID- 21975003 TI - Urinary mycoestrogens, body size and breast development in New Jersey girls. AB - BACKGROUND: Despite extensive research and interest in endocrine disruptors, there are essentially no epidemiologic studies of estrogenic mycotoxins, such as zeranol and zearalenone (ZEA). ZEA mycoestrogens are present in grains and other plant foods through fungal contamination, and in animal products (e.g., meat, eggs, dairy products) through deliberate introduction of zeranol into livestock to enhance meat production, or by indirect contamination of animals through consumption of contaminated feedstuff. Zeranol is banned for use in animal husbandry in the European Union and other countries, but is still widely used in the US. Surprisingly, little is known about the health effects of these mycoestrogens, including their impact on puberty in girls, a period highly sensitive to estrogenic stimulation. OBJECTIVES AND METHODS: We conducted a cross sectional analysis among 163 girls, aged 9 and 10 years, participating in the Jersey Girl Study to measure urinary mycoestrogens and their possible relationship to body size and development. RESULTS: We found that mycoestrogens were detectable in urine in 78.5% of the girls, and that urinary levels were predominantly associated with beef and popcorn intake. Furthermore, girls with detectable urinary ZEA mycoestrogen levels tended to be shorter and less likely to have reached the onset of breast development. CONCLUSIONS: Our findings suggest that ZEA mycoestrogens may exert anti-estrogenic effects similar to those reported for isoflavones. To our knowledge, this was the first evaluation of urinary mycoestrogens and their potential health effects in healthy girls. However, our findings need replication in larger studies with more heterogeneous populations, using a longitudinal approach. PMID- 21975004 TI - High temperature effects on out-patient visits and hospital admissions in Chiang Mai, Thailand. AB - OBJECTIVES: This study investigated the short-term effects of temperature on out patient visits and hospital admissions in Chiang Mai, Thailand. While mortality outcomes in the literature have been reported, there is less evidence of morbidity effects with very few studies conducted in developing countries with subtropical or tropical climate. METHODS: Time-series regression analysis was employed using generalized negative binomial regression to model the short-term relationships between temperature and morbidity after controlling for seasonal patterns and other potential confounders. Lag effects up to 13 days and effect modification by age (0-14 years, 15-64 years, >=65 years) were examined. RESULTS: Temperature effects with wide confidence intervals were found, with an increase in diabetic visits of 26.3% (95% CI: 7.1%-49.0%), and circulatory visits of 19.2% (95% CI: 7.0%-32.8%) per 1 degrees C increase in temperature above an identified threshold of 29 degrees C. Additionally, there was a rise of both visits (3.7% increase, 95% CI: 1.5%-5.9%) and admissions (5.8% increase, 95% CI: 2.3%-9.3%) due to intestinal infectious disease in association with each 1 degrees C increase across the whole temperature range. The effects of temperature were stronger in the elderly though not statistically significant. CONCLUSIONS: Daily morbidity in Chiang Mai was positively associated with temperature with a lag effect of up to 2 weeks, which was longer than lag effects previously reported. Public health preparedness and interventions should be considered to minimise possible increased hospital visits and admissions during hot weather. PMID- 21975006 TI - Nationwide monitoring of selected antibiotics: Distribution and sources of sulfonamides, trimethoprim, and macrolides in Japanese rivers. AB - We report the results of a nationwide survey of commonly used human and veterinary antibiotics (7 sulfonamides, trimethoprim, and 4 macrolides) in 37 Japanese rivers. Concentrations of the sum of the 12 target antibiotics ranged from undetectable to 626 ng/L, with a median of 7.3 ng/L for the 37 rivers. Antibiotics concentrations were higher in urban rivers than in rural rivers and were correlated with those of molecular markers of sewage (crotamiton and carbamazepine). Macrolides were dominant over sulfonamides in urban rivers. Sulfonamides, especially sulfamethazine (used in animals), were dominant in a few rivers in whose catchment animal husbandry is active. However, these signals of veterinary antibiotics were overwhelmed by those of human antibiotics in lower reaches of most rivers. The analysis of the antibiotics in all 88 samples showed that the target antibiotics in Japanese rivers are derived mainly from urban sewage, even though larger amounts of antibiotics are used in livestock. Most of the livestock waste-derived antibiotics are unlikely to be readily discharged to surface waters. PMID- 21975007 TI - Phytotoxicity and uptake of nitroglycerin in a natural sandy loam soil. AB - Nitroglycerin (NG) is widely used for the production of explosives and solid propellants, and is a soil contaminant of concern at some military training ranges. NG phytotoxicity data reported in the literature cannot be applied directly to development of ecotoxicological benchmarks for plant exposures in soil because they were determined in studies using hydroponic media, cell cultures, and transgenic plants. Toxicities of NG in the present studies were evaluated for alfalfa (Medicago sativa), barnyard grass (Echinochloa crusgalli), and ryegrass (Lolium perenne) exposed to NG in Sassafras sandy loam soil. Uptake and degradation of NG were also evaluated in ryegrass. The median effective concentration values for shoot growth ranged from 40 to 231 mg kg(-1) in studies with NG freshly amended in soil, and from 23 to 185 mg kg(-1) in studies with NG weathered-and-aged in soil. Weathering-and-aging NG in soil did not significantly affect the toxicity based on 95% confidence intervals for either seedling emergence or plant growth endpoints. Uptake studies revealed that NG was not accumulated in ryegrass but was transformed into dinitroglycerin in the soil and roots, and was subsequently translocated into the ryegrass shoots. The highest bioconcentration factors for dinitroglycerin of 685 and 40 were determined for roots and shoots, respectively. Results of these studies will improve our understanding of toxicity and bioconcentration of NG in terrestrial plants and will contribute to ecological risk assessment of NG-contaminated sites. PMID- 21975008 TI - The effect of nitrate, bicarbonate and natural organic matter on the degradation of sunscreen agent p-aminobenzoic acid by simulated solar irradiation. AB - Our experiments revealed that a model sunscreen agent, p-aminobenzoic acid (PABA), can be effectively transformed through reactions that are mediated by simulated solar irradiation. We systematically explored the effects of nitrate ions, bicarbonate and different types of natural organic matter (NOM) on the degradation of PABA by simulated solar irradiation. Experimental data suggest that these components ubiquitous in nature water have different influence on the rates of the photoinduced removal of PABA. Products were extracted and analyzed using LC/MS and a total of four products probably resulting from OH and NO2 radicals attack were identified and the possible reaction pathways were proposed. The findings in this study provide useful information for understanding the environmental transformation of sunscreen agent in aquatic system. PMID- 21975009 TI - An old friend in a new light: the role of osteocalcin in energy metabolism. AB - Accumulating evidence suggests interactions between bone and energy metabolism, which may affect the risk of cardiovascular disease. Recent animal studies indicate that osteocalcin (OC) plays a key role in the coordinated regulation of glucose and insulin metabolism while insulin receptors on osteoblasts may regulate bone turnover and circulating OC levels. Association studies, weight loss interventions, and observational data lend some support to the existence and relevance of these mechanisms in humans. However, corroborating evidence from pharmacologic interventions in either bone or glucose metabolism is limited by the number, design, and complex pharmacological effects of the drugs used. Furthermore, such clinical trials are complicated by the alteration of metabolic feedback mechanisms in the insulin resistant state. Purpose-designed studies are needed to further establish the existence and significance of the role of OC and its subfractions in human insulin metabolism. In this review we summarize existing animal evidence regarding the role of OC and its subfractions in bone and energy metabolism and assess current clinical trial evidence relating to the significance and consequences of this relationship in humans. PMID- 21975011 TI - Patient and public involvement in pressure ulcer research. PMID- 21975012 TI - ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate transmembrane cargos in hESC-derived human neurons. AB - BACKGROUNDS: Endosomal sorting complex required for transport (ESCRT) is involved in several fundamental cellular processes and human diseases. Many mammalian ESCRT proteins have multiple isoforms but their precise functions remain largely unknown, especially in human neurons. RESULTS: In this study, we differentiated human embryonic stem cells (hESCs) into postmitotic neurons and characterized the functional properties of these neurons. Moreover, we found that among the three human paralogs of the yeast ESCRT-III subunit Snf7, hSnf7-1 and hSnf7-2 are most abundantly expressed in human neurons. Both hSnf7-1 and hSnf7-2 are required for the survival of human neurons, indicating a non-redundant essential function. Indeed, hSnf7-1 and hSnf7-2 are preferentially associated with CHMP2A and CHMP2B, respectively, and regulate the turnover of distinct transmembrane cargos such as neurotransmitter receptors in human neurons. CONCLUSION: These findings indicate that different mammalian paralogs of the yeast ESCRT-III subunit Snf7 have non redundant functions in human neurons, suggesting that ESCRT-III with distinct subunit compositions may preferentially regulate different cargo proteins. PMID- 21975014 TI - Foot-and-mouth disease virus (FMDV) leader proteinase negatively regulates the porcine interferon-lambda1 pathway. AB - Foot-and-mouth disease is a highly contagious viral disease caused by foot-and mouth disease virus (FMDV) of wild and domestic cloven-hoofed animals, and causes an economically important disease in the swine industry. In this study, we found that the replication of FMDV in IBRS-2 cells could be significantly inhibited after treatment with the purified recombinant porcine interferon lambda 1 (IFN lambda1), a newly identified type III interferon. However, FMDV could not activate the IFN-lambda1 promoter and IFN-lambda1 mRNA expression in infected IBRS-2 cells, suggesting that FMDV has evolved mechanisms to interrupt the antiviral function of IFN-lambda1. The cause of this inhibition was determined by screening all structural and non-structural proteins of FMDV, and the leader proteinase (L(pro)) was found to exhibit the highest potential to inhibit poly(I:C)-induced IFN-lambda1 promoter activity. Further study revealed that the catalytic activity and a SAP (SAF-A/B, Acinus, and PIAS) domain of L(pro) were required for suppressing poly(I:C)-induced IFN-lambda1 production. These data suggest that FMDV replication could be inhibited by porcine IFN-lambda1, but that the virus has evolved specific mechanisms to inhibit this action. PMID- 21975015 TI - The association between cigarette smoking and multiple sclerosis. AB - Genetic factors partially explain the susceptibility of multiple sclerosis (MS) and might even relate to the clinical course. Still, many epidemiological studies point at an important role for environmental factors in MS. Smoking is one of the major candidates. In this review we provide an overview of the epidemiological studies on cigarette smoking and the association on MS risk and MS clinical course. In addition, we discuss the possible biological pathways that may influence neurological damage in MS. Moreover, the relation of smoking with other environmental MS risk factors will be addressed. PMID- 21975016 TI - Cerebral oxygen metabolism in patients with early Parkinson's disease. AB - AIM: Decreased activity of the mitochondrial electron transport chain (ETC) has been implicated in the pathogenesis of Parkinson's disease (PD). This model would most likely predict a decrease in the rate of cerebral oxygen consumption (CMRO(2)). To test this hypothesis, we compared CMRO(2) and cerebral blood flow (CBF) PET scans from PD patients and healthy controls. MATERIALS AND METHODS: Nine early-stage PD patients and 15 healthy age-matched controls underwent PET scans for quantitative mapping of CMRO(2) and CBF. Between-group differences were evaluated for absolute data and intensity-normalized values. RESULTS: No group differences were detected in regional magnitudes of CMRO(2) or CBF. Upon normalization using the reference cluster method, significant relative CMRO(2) decreases were evident in widespread prefrontal, parieto-occipital, and lateral temporal regions. Sensory-motor and subcortical regions, brainstem, and the cerebellum were spared. A similar pattern was evident in normalized CBF data, as described previously. CONCLUSION: While the data did not reveal substantially altered absolute CMRO(2) in brain of PD patients, employing data-driven intensity normalization revealed widespread relative CMRO(2) decreases in cerebral cortex. The detected pattern was very similar to that reported in earlier CBF and CMRglc studies of PD, and in the CBF images from the same subjects. Thus, the present results are consistent with the occurrence of parallel declines in CMRO(2), CBF, and CMRglc in spatially contiguous cortical regions in early PD, and support the hypothesis that ETC dysfunction could be a primary pathogenic mechanism in early PD. PMID- 21975018 TI - Selective inhibition of GluN2D-containing N-methyl-D-aspartate receptors prevents tissue plasminogen activator-promoted neurotoxicity both in vitro and in vivo. AB - BACKGROUND: Tissue plasminogen activator (tPA) exerts multiple functions in the central nervous system, depending on the partner with which it interacts. In particular, tPA acts as a positive neuromodulator of N-methyl-D-aspartate glutamatergic receptors (NMDAR). At the molecular level, it has been proposed that the pro-neurotoxicity mediated by tPA might occur through extrasynaptic NMDAR containing the GluN2D subunit. Thus, selective antagonists targeting tPA/GluN2D-containing NMDAR signaling would be of interest to prevent noxious effects of tPA. RESULTS: Here, we compared three putative antagonists of GluN2D containing NMDAR and we showed that the new compound UBP145 ((2R*,3S*)-1-(9 bromophenan-threne-3-carbonyl)piperazine-2,3-dicarboxylic acid) is far more selective for GluN2D subunits than memantine and PPDA (phenanthrene derivative (2S*, 3R*)-1-(phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid). Indeed, in vitro, in contrast to the two other compounds, UBP145 prevented NMDA toxicity only in neurons expressing GluN2D (ie, in cortical but not hippocampal neurons). Furthermore, in cultured cortical neurons, UBP145 fully prevented the pro excitotoxic effect of tPA. In vivo, we showed that UBP145 potently prevented the noxious action of exogenous tPA on excitotoxic damages. Moreover, in a thrombotic stroke model in mice, administration of UBP145 prevented the deleterious effect of late thrombolysis by tPA. CONCLUSIONS: In conclusion, tPA exerts noxious effects on neurons by acting on GluN2D-containing NMDAR and pharmacological antagonists of GluN2D-containing NMDAR could be used to prevent the ability of tPA to promote neurotoxicity. PMID- 21975017 TI - XVI European Charcot Foundation lecture: nutrition and environment: can MS be prevented? AB - Multiple sclerosis (MS) is a relatively common debilitating neurologic disease that affects people in early adulthood. While the characteristic pathology of MS has been well described, the etiology of the disease is not well understood, despite decades of research and the identification of strong genetic and environmental candidates for susceptibility. A question central to all diseases, but posed specifically for MS at the XVI European Charcot Foundation Lecture, was 'Can MS be prevented?' To address this question, we have evaluated the available data regarding nutritional and environmental factors that may be related to MS susceptibility and suggest the extent to which a potential intervention may reduce disease burden. It is our opinion that intervention, particularly supplementation with vitamin D, could have a dramatic impact on disease prevalence. Understanding that any intervention or behavioral modification will surely act in the context of genetic susceptibility and unidentified stochastic events, it is likely that not all MS is 'preventable'. Epidemiologic observation has provided key insights into environmental and nutritional factors that may alter one's susceptibility to MS, however, there are still many questions in unraveling the etiology of this complex disease. PMID- 21975020 TI - Application of liquid chromatography-direct-electron ionization-MS in an in vitro dermal absorption study: quantitative determination of trans-cinnamaldehyde. AB - We propose a new analytical approach, based on liquid chromatography (LC) coupled to electron ionization mass spectrometry (EI-MS), using a Direct-EI interface, for dermal absorption evaluation studies. Penetration through the skin of a given compound is evaluated by means of in vitro assays using diffusion cells. Currently, the most popular approach for the analysis of skin and fluid samples is LC coupled to electrospray ionization tandem mass spectrometry (ESI-MS/MS). However, this technique is largely affected by sample matrix interferences that heavily affect quantitative evaluation. LC-Direct-EI-MS is not affected by matrix interference and produces accurate quantitative data in a wide range of concentrations. Trans-cinnamaldehyde was chosen as test substance and applied in a suitable dosing vehicle on dermatomed human skin sections. This compound was then quantified in aliquots of receptor solution, skin extract, cell wash, skin wash, carbon filter extract, cotton swab extract, and tape strip digest. On column limits of detection (LOD) and limits of quantitation (LOQ) of 0.1 and 0.5 ng/MUL, respectively, were achieved. Calibration showed satisfactory linearity and precision for the concentration range of interest. Matrix effects (ME) were evaluated for all sample types, demonstrating the absence of both signal enhancement and signal suppression. The Direct-EI absorption profile was compared with that obtained with liquid scintillation counting (LSC), a recognized ME free approach. A good correlation was found with all samples and for the overall recovery of the dosed substance. PMID- 21975019 TI - The epidemic of sexually transmitted infections in China: implications for control and future perspectives. AB - China has experienced an increasing epidemic of sexually transmitted infections (STIs), including HIV. High risk groups likely to be infected include female sex workers (FSWs) and their clients, men who have sex with men (MSM), drug users and migrant workers. Prevention can be achieved through education of the population, condom promotion, early detection of symptomatic and asymptomatic people, and effective diagnosis and treatment of these patients and their partners. This article aims to describe the profile of the epidemic in high-risk groups in China as well as to detail the contributing factors and the implications for control. Programmes for the control of STIs should be immediate priorities in China, and primary and secondary prevention strategies are vital to this process. PMID- 21975021 TI - Chemical profiling of the cytotoxic triterpenoid-concentrating fraction and characterization of ergostane stereo-isomer ingredients from Antrodia camphorata. AB - Antrodia camphorata (AC), also known as Antrodia cinnamomea, an endemic species in Taiwan, is one of the treasured medicinal mushrooms. AC is traditionally used for its chemopreventive biofunctions. In this investigation, we report a convenient method for concentrating the antiproliferative active triterpenoid rich fraction (FEA), from ethanolic extract of AC (EEAC). A series of stereo isomers of zhankuic acids (1-8) from the FEA was purified by HPLC using an efficient acidic solvent system. The structures of compounds 1-8 were elucidated based on spectroscopic data analysis, and the absolute configuration of alpha chiral carboxylic acid at C-25 in the structures was assigned based on reaction with (R)- and (S)-1-(9-anthryl)-2,2,2-trifluoroethanol. Major ingredients of FEA (eight ergostanes 1-8 and two lanostanes 9-10) were further characterised by high performance liquid chromatography-photodiode array detection/mass spectrometry (HPLC-PDA/MS). Compounds 1-8 and their pair mixture forms (antcin K, antcin C, zhankuic acid C, and zhankuic acid A) were subjected to anti-proliferative assay against three human leukemia cell lines. Among them, the derivatives with carbonyl group at C-3 showed cytotoxicity with IC(50) values ranging from 16.44 to 77.04 MUg/ml. PMID- 21975022 TI - High-resolution imaging and antitumor effects of GFP(+) bone marrow-derived cells homing to syngeneic mouse colon tumors. AB - Bone marrow-derived cells (BMDCs) participate in the growth and spread of tumors of the breast, brain, lung, and stomach. To date, there are limited reports of bone marrow involvement in colon cancer pathogenesis, but such findings would have the potential to generate novel treatments for colon cancer patients. We have established a mouse model for imaging BMDCs from whole tumor to single-cell resolution, whereby the bone marrow of lethally irradiated host animals is reconstituted with EGFP-expressing bone marrow cells from matched TgActb(EGFP) donors. The BM transplants yield mice with fluorescently labeled bone marrow, and so BMDCs can subsequently be monitored within a tumor through optical imaging. Successful BM reconstitution was confirmed at 8 weeks after transplantation, when surviving BALB/c mice were injected with CT26 mouse colon cancer cells. We find that up to 45% of cells dissociated from the tumors are GFP(+) and approximately 50% of Lin(+), CD11b(+), and CD3(+) cells express high levels of GFP. Notably, tumor growth is reduced in BM transplanted animals, compared with untransplanted host mice or EGFP-expressing BM donor mice. A needed next step is to separate the molecular and cellular (eg, T cells, NK cells, macrophages) bases of the antitumor effect of the BMDCs from any protumorigenic effect that could be subverted for therapeutic gain. PMID- 21975023 TI - Early mortality and overall survival in oncology phase I trial participants: can we improve patient selection? AB - BACKGROUND: Patient selection for phase I trials (PIT) in oncology is challenging. A typical inclusion criterion for PIT is 'life expectancy > 3 months', however the 90 day mortality (90DM) and overall survival (OS) of patients with advanced solid malignancies are difficult to predict. METHODS: We analyzed 233 patients who were enrolled in PIT at Princess Margaret Hospital. We assessed the relationship between 17 clinical characteristics and 90DM using univariate and multivariate logistic regression analyses to create a risk score (PMHI). We also applied the Royal Marsden Hospital risk score (RMI), which consists of 3 markers (albumin < 35g/L, > 2 metastatic sites, LDH > ULN). RESULTS: Median age was 57 years (range 21-88). The 90DM rate was 14%; median OS was 320 days. Predictors of 90DM were albumin < 35g/L (OR = 8.2, p = 0.01), > 2 metastatic sites (OR = 2.6, p = 0.02), and ECOG > 0 (OR = 6.3, p = 0.001); all 3 factors constitute the PMHI. To predict 90DM, the PMHI performed better than the RMI (AUC = 0.78 vs 0.69). To predict OS, the RMI performed slightly better (RMI >= 2, HR = 2.2, p = 0.002 vs PMHI >= 2, HR = 1.6, p = 0.05). CONCLUSIONS: To predict 90DM, the PMHI is helpful. To predict OS, risk models should include ECOG > 0, > 2 metastatic sites, and LDH > ULN. Prospective validation of the PMHI is warranted. PMID- 21975024 TI - Past and current alcohol consumption patterns and elevations in serum hepatic enzymes among US adults. AB - OBJECTIVE: The aim of this study was to examine the association between patterns of past and current alcohol consumption and elevations in serum hepatic enzymes among a nationally representative sample of adults in the United States. METHODS: We estimated the age-adjusted prevalence of elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyltransferase (GGT) among 8993 adults aged 20 years or older who participated in the 2005-2008 National Health and Nutrition Examination Survey (NHANES). We produced prevalence ratios by using patterns of alcohol consumption as a predictor; elevations in serum ALT, AST, and GGT were used as an outcome variable while adjusting for covariates in multivariate regression models. RESULTS: The age-adjusted prevalence of elevated serum ALT, AST, and GGT in adults was 9.7%, 16.0%, and 8.6%, respectively. Male excessive current drinkers had 50%-71% and 75%-314% increased likelihoods of having elevated serum AST and GGT, respectively; female excessive drinkers with a history of consuming 5 or more drinks almost daily had a 226% increased likelihood of having elevated serum GGT, when compared to their respective counterparts who were lifetime abstainers. CONCLUSIONS: The results of this study indicate that elevations in serum hepatic enzymes, especially AST and GGT, are common in adults who are excessive current drinkers. There is evidence to suggest that excessive current drinkers with a history of protracted drinking are especially vulnerable to potential liver injury. These findings lend further support to the early identification of excessive drinkers who may have an increased risk for alcohol-related morbidity and mortality in health care settings. PMID- 21975025 TI - Aging in neighborhoods differing in walkability and income: associations with physical activity and obesity in older adults. AB - While there is a growing literature on the relations between neighborhood design and health factors such as physical activity and obesity, less focus has been placed on older adults, who may be particularly vulnerable to environmental influences. This study evaluates the relations among objectively measured neighborhood design, mobility impairment, and physical activity and body weight in two U.S. regional samples of community dwelling older adults living in neighborhoods differing in walkability and income levels. An observational design involving two time points six months apart was employed between 2005 and 2008. U.S. Census block groups in Seattle-King County, Washington and Baltimore, Maryland-Washington DC regions were selected via geographic information systems to maximize variability in walkability and income. Participants were 719 adults ages 66 years and older who were able to complete surveys in English and walk at least 10 feet continuously. Measurements included reported walking or bicycling for errands (i.e., transport activity) and other outdoor aerobic activities measured via the CHAMPS questionnaire: accelerometry-based moderate-to-vigorous physical activity; reported body mass index; and reported lower extremity mobility impairment measured via the Late-Life Function and Disability Instrument. Across regions, time, and neighborhood income, older adults living in more walkable neighborhoods had more transport activity and moderate-to- vigorous physical activity and lower body mass index relative to those living in less walkable neighborhoods. The most mobility-impaired adults living in more walkable neighborhoods reported transport activity levels that were similar to less mobility-impaired adults living in less walkable neighborhoods. The results add to the small literature aimed at understanding how neighborhood design may influence physical activity and related aspects of health linked with day-to-day function and independence as people age. PMID- 21975026 TI - Allocation of household responsibilities influences change in dietary behavior. AB - This study was undertaken to understand dietary behavior as situated within the household, an important social context that serves to either inhibit or promote a healthy diet. Data were collected as part of a worksite-based health behavior intervention trial that took place between 1999 and 2003 in small manufacturing businesses in New England, U.S.A. The subjects were a cohort of 790 male and female workers who participated in the intervention trial and responded to both the baseline and the 18-month follow-up surveys. Regression models were built to determine whether proportion of household responsibility predicted daily fruit and vegetable consumption and weekly red meat consumption at 18-months. The results indicate that participants who were responsible for earning most or all of the money to support the household ate more servings of fruits and vegetables per day at 18-month follow-up than those without this responsibility. Further, those responsible for earning about half ate fewer servings of red meat than those responsible for earning most or all of the money to support the household. The results for red meat consumption differed by sex, such that responsibility for more than half or less than half of the money to support the household had different effects for men and women. The results of this study demonstrate that the distribution of household responsibilities can be an important factor in determining the effectiveness of a worksite-based health behavior intervention and that these effects can be different for women versus men. PMID- 21975027 TI - Why is U.K. medicine no longer a self-regulating profession? The role of scandals involving "bad apple" doctors. AB - This article identifies the role played by a series of medical scandals in the U.K., occurring from the mid-1990s onwards, in ending a collegial model of self regulation of the medical profession that had endured for 150 years. The state's original motive in endorsing professional self-regulation was to resolve the principal-agent problem inherent in the doctor-patient relationship. The profession, in return for its self-regulating privileges, undertook to act as a reliable guarantor for the competence and conduct of each of its members. Though sufficient to ensure that most doctors were "good", the collegial model adopted by the profession left it fatally vulnerable to the problem of "bad apples": those unwilling, incapable or indifferent to delivering on their professional commitments and who betrayed the trust of both patients and peers. Weak administrative systems in the NHS failed to compensate for the defects of the collegium in controlling these individuals. The scandals both provoked and legitimised erosion of the profession's self-regulatory power. Though its vulnerability to bad apples had been present since the founding of the 19th century profession, it was the convergence of social and political conditions at a particular historical moment that transformed the scandals into an unstoppable imperative for reform. Huge public anger, the voice permitted to a coalition of critics, shifts in social attitudes, the opportunity presented for imposing standards for accountability, and the increasing ascendancy of pro interventionist managerialist and political agendas from the early 1990s onwards were all implicated in the response made to scandals and the shape the reforms took. Scandals need to be understood not as simple determinants of change, but as one performative element in a constellation of socially contingent forces and contexts. The new rebalancing of the "countervailing powers" has dislodged the profession as the senior partner in the regulation of doctors, but may introduce new risks. PMID- 21975028 TI - The costs of infection and resistance as determinants of West Nile virus susceptibility in Culex mosquitoes. AB - BACKGROUND: Understanding the phenotypic consequences of interactions between arthropod-borne viruses (arboviruses) and their mosquito hosts has direct implications for predicting the evolution of these relationships and the potential for changes in epidemiological patterns. Although arboviruses are generally not highly pathogenic to mosquitoes, pathology has at times been noted. Here, in order to evaluate the potential costs of West Nile virus (WNV) infection and resistance in a primary WNV vector, and to assess the extent to which virus vector relationships are species-specific, we performed fitness studies with and without WNV exposure using a highly susceptible Culex pipiens mosquito colony. Specifically, we measured and compared survival, fecundity, and feeding rates in bloodfed mosquitoes that were (i) infected following WNV exposure (susceptible), (ii) uninfected following WNV exposure (resistant), or (iii) unexposed. RESULTS: In contrast to our previous findings with a relatively resistant Cx. tarsalis colony, WNV infection did not alter fecundity or blood-feeding behaviour of Cx. pipiens, yet results do indicate that resistance to infection is associated with a fitness cost in terms of mosquito survival. CONCLUSIONS: The identification of species-specific differences provides an evolutionary explanation for variability in vector susceptibility to arboviruses and suggests that understanding the costs of infection and resistance are important factors in determining the potential competence of vector populations for arboviruses. PMID- 21975029 TI - Dose of enoxaparin in review of rivaroxaban versus enoxaparin for prophylaxis of venous thromboembolism. PMID- 21975030 TI - Risk of bleeding in low-risk atrial fibrillation patients on warfarin waiting for elective cardioversion. AB - INTRODUCTION: Systemic embolism is the most serious complication of cardioversion of atrial fibrillation (AF) and the immediate post-cardioversion period is associated with increased risk for thrombus formation. For this reason, treatment with vitamin K antagonist (VKA) is recommended for patients with AF. No information is available about bleeding risk related to this practice. METHODS: We performed a prospective multicentre study on 242 low-risk AF patients (CHADS(2) score 0-1) that started on warfarin for elective cardioversion to evaluate their bleeding risk. RESULTS: 178 were males (73.6%), mean age 63.9 +/- 9.8 years, 60 patients (25%) were aged <= 59 years. Patients with CHADS(2) score = 0 were 73 (30%), those with CHADS(2) score = 1 were 169 (70%). Patients were on VKA treatment, maintained at INR intended therapeutic range 2.0-3.0, for a median time of 159 days (range 30-631)total follow-up period 127 patient-years (pt-yrs). Quality of anticoagulation and occurrence of bleeding events were recorded. Patients spent 23%, 64% and 8% of time below, within and above the intended therapeutic range, respectively. When we observed the INR levels, we found that 62 patients (25.6%) had INR>4.5 at least in one occasion, and 23 (9.5%) in >= 2. During follow-up, 2 patients had major bleeds (rate 1.6% pt-yrs), one fatal. No embolic complications were recorded. CONCLUSION: Our results show that low-risk AF patients, treated with VKA for elective cardioversion, carry a not irrelevant risk of bleeding. Efforts are required to properly select patients who could benefit from this procedure, reducing the time of warfarin exposure. PMID- 21975031 TI - Systemic and local factors associated with coronary plaque disruption. AB - INTRODUCTION: Yellow plaques are regarded vulnerable; and disrupted yellow plaques are the major cause of acute coronary syndrome. We examined the factors associated with the disruption of yellow plaques among patients and lesion characteristics. MATERIALS AND METHODS: Consecutive 161 patients with ischemic heart diseases who received coronary angioscopic examination were analyzed. Yellow plaques in the segments to which intervention had never been performed were included, and their yellow color grade and presence/ absence of disruption were examined. Associated factors for plaque disruption were examined among patients and lesion characteristics. RESULTS: In 161 patients, 392 yellow plaques were included for analysis and 70 of them were disrupted. Frequency of plaque disruption (=disrupted / all yellow plaques) was significantly higher at the segments of severer stenosis (stenosis>=75% vs. 75-25% vs. <25%: 34% vs. 21% vs. 14%, p=0.006). Multivariate analysis revealed angiographic stenosis (odds ratio [OR], 1.014; 95% confidence interval [CI], 1.005-1.023; p=0.003), yellow color grade (OR, 3.297; 95% CI, 2.062-5.273, p<0.001), LDL-cholesterol (OR, 1.012; 95% CI, 1.004-1.020, p=0.003), male gender (OR, 3.608; 95% CI, 1.538-8.465; p=0.003), and hypertension (OR, 2.552; 95% CI, 1.094-5.953; p=0.030) as significant associated factors for plaque disruption. CONCLUSION: Angiographic stenosis, yellow color grade, LDL-cholesterol, male gender, and hypertension were significantly associated with the disruption of yellow plaques. PMID- 21975032 TI - Protein Z/protein Z-dependent protease inhibitor system in human non-small-cell lung cancer tissue. AB - INTRODUCTION: NSCLC progression is often associated with VTE. Activation of factor X is an important step in blood coagulation activation in cancer patients. PZ)/ZPI contribute to direct factor Xa inhibition, and ZPI - attenuates factors IXa and XIa activity. The role of the PZ/ZPI in NSCLC is obscure. The aim of the study was to localize ZPI and PZ in NSCLC tissue in relation to factors X, IX and XI, as well as indicators of blood coagulation activation: prothrombin fragment F1+2 (F1+2) and fibrin. MATERIAL & METHODS: Immunohistochemical studies were performed on surgical NSCLC specimens employing antibodies against ZPI, PZ, coagulation factors X, IX, XI, as well as fibrinogen, F1+2 and fibrin. A semiquantitative analysis (acc. to immunoreactive score-IRS) was conducted. RESULTS: Medium expression of ZPI(IRS=6.5), together with weak expression of PZ(IRS=4), was observed in cancer cells. Strong or medium staining for factors IX, X, and XI(IRS=8-9) was revealed in cancer cells. Fibrinogen(IRS=10) and fibrin(IRS=8) were demonstrated in tumor stroma and cancer cells. F1+2(IRS=10) was localized in NSCLC cells. Endothelial cells (ECs) and tumor infiltrating macrophages (TAMs) were characterized by a positive staining for ZPI and PZ. CONCLUSIONS: ZPI and PZ expression in NSCLC cells, ECs and TAMs may suggest a role for PZ/ZPI in the anticoagulant mechanisms at the tumor site. The presence of F1+2 and fibrin, along with a disproportional expression of ZPI and PZ, might point to impaired function of the coagulation inhibitory system in NSCLC tissue. PMID- 21975034 TI - Altered oxygen metabolism associated to neurogenesis of induced pluripotent stem cells derived from a schizophrenic patient. AB - Schizophrenia has been defined as a neurodevelopmental disease that causes changes in the process of thoughts, perceptions, and emotions, usually leading to a mental deterioration and affective blunting. Studies have shown altered cell respiration and oxidative stress response in schizophrenia; however, most of the knowledge has been acquired from postmortem brain analyses or from nonneural cells. Here we describe that neural cells, derived from induced pluripotent stem cells generated from skin fibroblasts of a schizophrenic patient, presented a twofold increase in extramitochondrial oxygen consumption as well as elevated levels of reactive oxygen species (ROS), when compared to controls. This difference in ROS levels was reverted by the mood stabilizer valproic acid. Our model shows evidence that metabolic changes occurring during neurogenesis are associated with schizophrenia, contributing to a better understanding of the development of the disease and highlighting potential targets for treatment and drug screening. PMID- 21975035 TI - Radiofrequency energy loop primes cardiac, neuronal, and skeletal muscle differentiation in mouse embryonic stem cells: a new tool for improving tissue regeneration. AB - Radiofrequency (RF) waves from Wi-Fi (wireless fidelity) technologies have become ubiquitous, with Internet access spreading into homes, and public areas. The human body harbors multipotent stem cells with various grading of potentiality. Whether stem cells may be affected by Wi-Fi RF energy remains unknown. We exposed mouse embryonic stem (ES) cells to a Radio Electric Asymmetric Conveyer (REAC), an innovative device delivering Wi-Fi RF of 2.4 GHz with its conveyer electrodes immersed into the culture medium. Cell responses were investigated by real-time PCR, Western blot, and confocal microscopy. Single RF burst duration, radiated power, electric and magnetic fields, specific absorption rate, and current density in culture medium were monitored. REAC stimulation primed transcription of genes involved in cardiac (GATA4, Nkx-2.5, and prodynorphin), skeletal muscle (myoD) and neuronal (neurogenin1) commitment, while downregulating the self renewal/pluripotency-associated genes Sox2, Oct4, and Nanog. REAC exposure enhanced the expression of cardiac, skeletal, and neuronal lineage-restricted marker proteins. The number of spontaneously beating ES derived myocardial cells was also increased. In conclusion, REAC stimulation provided a "physical milieu" optimizing stem cell expression of pluripotentiality and the attainment of three major target lineages for regenerative medicine, without using chemical agonists or vector-mediated gene delivery. PMID- 21975036 TI - Autobiographical memory in adults with autism spectrum disorder: the role of depressed mood, rumination, working memory and theory of mind. AB - Autobiographical memory difficulties have been widely reported in adults with autism spectrum disorder (ASD). The aim of the current study was to explore the potential correlates of autobiographical memory performance (including depressed mood, rumination, working memory and theory of mind) in adults with ASD, relative to a group of typical adults matched for age, gender and IQ. Results demonstrated that the adults with ASD reported higher levels of depressed mood and rumination than the typical adults, and also received lower scores on measures of theory of mind and working memory. Correlational analysis suggested that theory of mind and working memory were associated with autobiographical memory performance in the adults with ASD, but no significant relationships were observed between autobiographical memory, depressed mood and rumination in this group. To explore these patterns further, two cases of adults with a dual diagnosis of ASD and depression are discussed. These participants present a profile in line with the idea that depressed mood and rumination do not have the same influence on autobiographical memory in adults with ASD as they do in typical adults. PMID- 21975037 TI - Feasibility of exposure response prevention to treat repetitive behaviors of children with autism and an intellectual disability: a brief report. AB - There is a lack of evidence-based behavioral therapies or pharmacotherapies to treat repetitive behaviors found in autism. Effective behavioral therapies are needed to counter any negative consequences these behaviors may have on the child's early learning and socialization. The purpose of this proof-of-principle study was to test the feasibility of modifying exposure response prevention, an evidence-based strategy for obsessive-compulsive disorder, to treat the repetitive behaviors found in autism. Five school-aged participants (ages 5-11) diagnosed with an autism spectrum disorder participated in the study. Our preliminary findings suggest it is feasible, and potentially efficacious, to modify standard exposure response prevention to treat the specific forms of repetitive behaviors found in individuals with autism and comorbid intellectual disabilities. A larger clinical trial is needed to substantiate these preliminary findings. PMID- 21975038 TI - Versatility of PRMT5-induced methylation in growth control and development. AB - Arginine methylation governs important cellular processes that impact growth and proliferation, as well as differentiation and development. Through their ability to catalyze symmetric or asymmetric methylation of histone and non-histone proteins, members of the protein arginine methyltransferase (PRMT) family regulate chromatin structure and expression of a wide spectrum of target genes. Unlike other PRMTs, PRMT5 works in concert with a variety of cellular proteins including ATP-dependent chromatin remodelers and co-repressors to induce epigenetic silencing. Recent work also implicates PRMT5 in the control of growth promoting and pro-survival pathways, which demonstrates its versatility as an enzyme involved in both epigenetic regulation of anti-cancer target genes and organelle biogenesis. These studies not only provide insight into the molecular mechanisms by which PRMT5 contributes to growth control, but also justify therapeutic targeting of PRMT5. PMID- 21975040 TI - Amperometric biosensor based on multilayer containing carbon nanotube, plasma polymerized film, electron transfer mediator phenothiazine, and glucose dehydrogenase. AB - We report on a novel fabrication approach of amperometric biosensor based on multilayer films containing carbon nanotubes (CNT), a nano-thin plasma polymerized film (PPF), electron transfer mediator phenothiazine (PT), and enzyme glucose dehydrogenase (GDH). The configuration of the electrochemical electrode is sequentially composed of sputtered gold, acetonitrile PPF, PT, GDH, and acetonitrile PPF (denoted as PPF/GDH/PT/CNT/PPF/Au). First PPF deposited on Au acts as a permselective membrane and as a scaffold for CNT layer formation. Second PPF directly deposited on GDH acts as a matrix for enzyme immobilization. To facilitate the electrochemical communication between the CNT layer and GDH, CNT was treated with nitrogen plasma. The electron transfer mediator PT plays a role as the mediator in which the electron caused by enzymatic reaction transports to the electrode. The synergy between the mediator and CNT provides benefits in terms of lowering the operational potential and enhancing the sensitivity (current). The optimized glucose biosensor revealed a sensitivity of 5.1 +/- 0.9 MUA mM(-1) cm(-2) at + 0.2V vs. Ag/AgCl, linear dynamic range of 4.9 19 mM, and a response time of 5 +/- 1 s. Unlike conventional wet-chemical processes that are incompatible with mass production techniques, this dry chemistry procedure has great potential for enabling high-throughput production of bioelectronic devices. Furthermore, those devices can be applied and expands for the cell biological functional field as a useful, helpful, or indispensable tool. PMID- 21975039 TI - Generation of reactive oxygen species in 1-methyl-4-phenylpyridinium (MPP+) treated dopaminergic neurons occurs as an NADPH oxidase-dependent two-wave cascade. AB - BACKGROUND: Reactive oxygen species (ROS), superoxide and hydrogen peroxide (H2O2), are necessary for appropriate responses to immune challenges. In the brain, excess superoxide production predicts neuronal cell loss, suggesting that Parkinson's disease (PD) with its wholesale death of dopaminergic neurons in substantia nigra pars compacta (nigra) may be a case in point. Although microglial NADPH oxidase-produced superoxide contributes to dopaminergic neuron death in an MPTP mouse model of PD, this is secondary to an initial die off of such neurons, suggesting that the initial MPTP-induced death of neurons may be via activation of NADPH oxidase in neurons themselves, thus providing an early therapeutic target. METHODS: NADPH oxidase subunits were visualized in adult mouse nigra neurons and in N27 rat dopaminergic cells by immunofluorescence. NADPH oxidase subunits in N27 cell cultures were detected by immunoblots and RT PCR. Superoxide was measured by flow cytometric detection of H2O2-induced carboxy H2-DCFDA fluorescence. Cells were treated with MPP+ (MPTP metabolite) following siRNA silencing of the Nox2-stabilizing subunit p22phox, or simultaneously with NADPH oxidase pharmacological inhibitors or with losartan to antagonize angiotensin II type 1 receptor-induced NADPH oxidase activation. RESULTS: Nigral dopaminergic neurons in situ expressed three subunits necessary for NADPH oxidase activation, and these as well as several other NADPH oxidase subunits and their encoding mRNAs were detected in unstimulated N27 cells. Overnight MPP+ treatment of N27 cells induced Nox2 protein and superoxide generation, which was counteracted by NADPH oxidase inhibitors, by siRNA silencing of p22phox, or losartan. A two-wave ROS cascade was identified: 1) as a first wave, mitochondrial H2O2 production was first noted at three hours of MPP+ treatment; and 2) as a second wave, H2O2 levels were further increased by 24 hours. This second wave was eliminated by pharmacological inhibitors and a blocker of protein synthesis. CONCLUSIONS: A two-wave cascade of ROS production is active in nigral dopaminergic neurons in response to neurotoxicity-induced superoxide. Our findings allow us to conclude that superoxide generated by NADPH oxidase present in nigral neurons contributes to the loss of such neurons in PD. Losartan suppression of nigral-cell superoxide production suggests that angiotensin receptor blockers have potential as PD preventatives. PMID- 21975041 TI - Epilation for trachomatous trichiasis and the risk of corneal opacification. AB - PURPOSE: Eight million people have trachomatous trichiasis (TT). The World Health Organization (WHO) recommends entropion surgery for TT regardless of severity. However, epilation is widely practiced for treating minor TT (1-5 lashes touching the globe). We report the frequency and effectiveness of patient-initiated epilation and its relationship to corneal opacity. DESIGN: Cross-sectional baseline data of individuals recruited to 2 randomized, clinical trials. PARTICIPANTS: We included 2556 individuals (4310 eyes) with previously unoperated TT in >= 1 eye. METHODS: A single ophthalmologist examined all participants for signs of trachoma using WHO grading systems with additional assessment of entropion grading, location and number of trichiatic lashes, and evidence of epilation. A questionnaire enquired about epilation practices. MAIN OUTCOME MEASURES: The association between epilation and degree of corneal opacity. Epilation practices of TT patients. RESULTS: Central corneal scarring was present in 1436 (33%) eyes. Entropion was absent/mild in 2328 (54%) eyes, moderate in 1259 (29.2%), and severe in 723 (16.8%). The median number of lashes touching the eye was 2 (interquartile range, 1-5; range, 0-133). There was clinical evidence of epilation in 3018 (70%) eyes, of which 738 (24%) were successfully epilated (no lashes touching globe). Epilation was performed frequently (at least monthly in 3311 [76.8%] eyes), by someone other than the patient (92.8%), and using locally made forceps (88.9%). Controlling for age and degree of entropion, successful epilation was associated with less corneal opacity (odds ratio [OR], 0.61; 95% confidence interval [CI]. 0.43-0.88; P = 0.007). The association was only significant in patients with severe entropion (OR, 0.07; 95% CI, 0.02-0.25; P<0.005). CONCLUSIONS: We found an association between successful epilation and less central corneal opacity. This indicates the importance of preventing eyelashes from touching the cornea, particularly in individuals with severe entropion. This is a cross-sectional study; therefore, a causative relationship cannot be concluded. However, the results suggest that among patients who decline or are unable to access surgery, and perhaps in minor TT where the management remains controversial, the provision of high-quality forceps and epilation training may be beneficial. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article. PMID- 21975042 TI - Minimal exposure (one or two cycles) of intra-arterial chemotherapy in the management of retinoblastoma. AB - PURPOSE: To assess the efficacy of less than 3 cycles of intra-arterial chemotherapy (IAC) for retinoblastoma. DESIGN: Retrospective, nonrandomized, interventional case series. PARTICIPANTS: Eight patients. INTERVENTION: Intra arterial chemotherapy. MAIN OUTCOME MEASURES: Tumor control and globe salvage. RESULTS: Eight patients received fewer than 3 cycles of IAC for retinoblastoma because there was complete tumor control with no residual viable tumor (n = 7) or poor response (n = 1) with little hope that further therapy would benefit the patient. In 3 cases, additional vascular compromise precluded further IAC. The treatment was primary in 6 cases and secondary after failure of other treatment in 2 cases. The 8 eyes were classified (International Classification of Retinoblastoma) as group C (n = 2), group D (n = 3), group E (n = 1), and secondary treatment (n = 2). At initial examination, the main tumor showed a mean basal diameter of 16 mm, a thickness of 8.6 mm, vitreous seeds (n = 2), subretinal seeds (n = 6), and iris neovascularization (n = 1). Three patients were treated with a single cycle of IAC, and 5 patients were treated with 2 cycles of IAC. After IAC, complete tumor response was found in 7 eyes (88%) and partial response was found in 1 eye (13%). Over a mean of 13 months follow-up, there was intraretinal tumor recurrence (n = 1), subretinal seed recurrence (n = 1), and no case of vitreous seed recurrence. Globe salvage was achieved in 2 of 2 group C eyes (100%), 3 of 3 group D eyes (100%), 0 of 1 group E eye (0%), and 1 of 2 secondary treatment eyes (50%). Globe salvage was achieved in 6 of 8 eyes (75%), and 2 of 8 eyes (25%) required enucleation. CONCLUSIONS: One or 2 cycles of IAC can be sufficient for selected eyes with group C or D retinoblastoma, with remarkable tumor control. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. PMID- 21975043 TI - The structure, properties, and nature of HArF-benzene complex: redshift and blueshift of Ar-H stretch frequency and rare gas atomic number dependence of hydrogen bonds. AB - Ab initio calculations have been performed for the complexes of benzene with HArF, HKrF, and HXeF. The computed results indicate that the complexes of benzene HArF exist in different conformations and among them those with pi-hydrogen bonds are the more stable than those with C-H...F hydrogen bonds. Interestingly, the Ar H stretching frequency is redshifted in the more stable isomer and blueshifted in the less stable form. The Ng (Ng=Ar, Kr, and Xe) atomic number dependence of the Ng-H...pi and C-H...F hydrogen bonds has been explored. The result indicates that the strength of Ng-H...pi and C-H...F hydrogen bonds is weakened with the increase of Ng atomic number. Natural bond orbital analysis has been performed to understand the interaction nature, frequency shift of H-Ng stretch, and dependence of Ng-H...pi and C-H...F hydrogen bonds on the Ng atomic number. PMID- 21975044 TI - Ultrasound-mediated structural changes in cells revealed by FTIR spectroscopy: a contribution to the optimization of gene and drug delivery. AB - Ultrasound effects on biological samples are gaining a growing interest concerning in particular, the intracellular delivery of drugs and genes in a safe and in a efficient way. Future progress in this field will require a better understanding of how ultrasound and acoustic cavitation affect the biological system properties. The morphological changes of cells due to ultrasound (US) exposure have been extensively studied, while little attention has been given to the cells structural changes. We have exposed two different cell lines to 1 MHz frequency ultrasound currently used in therapy, Jurkat T-lymphocytes and NIH-3T3 fibroblasts, both employed as models respectively in the apoptosis and in the gene therapy studies. The Fourier Transform Infrared (FTIR) Spectroscopy was used as probe to reveal the structural changes in particular molecular groups belonging to the main biological systems. The genotoxic damage of cells exposed to ultrasound was ascertained by the Cytokinesis-Block Micronucleus (CBMN) assay. The FTIR spectroscopy results, combined with multivariate statistical analysis, regarding all cellular components (lipids, proteins, nucleic acids) of the two cell lines, show that Jurkat cells are more sensitive to therapeutic ultrasound in the lipid and protein regions, whereas the NIH-3T3 cells are more sensitive in the nucleic acids region; a meaningful genotoxic effect is present in both cell lines only for long sonication times while in the Jurkat cells also a significant cytotoxic effect is revealed for long times of exposure to ultrasound. PMID- 21975045 TI - Influence of sodium fluoride (NaF) on the crystallization and spectral properties of L-tyrosine. AB - L-Tyrosine (C(9)H(11)NO(3)) is an essential amino acid in living organisms. It is also a building unit in protein, takes part in bio-synthesis of hormones, neurotransmitters, pigments and one of the organic chemical constituents of urinary stones. L-Tyrosine has been crystallized in silica gel by double diffusion technique with and without the addition of NaF. The crystals had rosette-like shape. In case of fluoride addition, two types of crystals have formed: rosette like crystallites, at the gel-solution interface and reticulate type crystallites beneath the interface. XRD results confirmed that both the products are of l-tyrosine with identical crystal structures. Crystal structure, morphology, thermal and spectral properties are analyzed using powder X-ray diffraction (XRD), scanning electron microscopy (SEM), thermogravimetric and differential thermal analysis (TG-DTA), Fourier transform infrared spectroscopy (FTIR) and UV-vis transmittance studies. The TG-DTA results suggest that the thermal stability of L-tyrosine has markedly improved due to fluoride doping. Optical band gap energy of NaF grown l-tyrosine crystallite is estimated as 4.28eV. Second harmonic generation efficiency test indicates that L-tyrosine crystals can be used for application in nonlinear optical devices. PMID- 21975046 TI - Mie lidar observations of lower tropospheric aerosols and clouds. AB - Mie lidar system is developed at Laser Science and Technology Centre, Delhi (28.38 degrees N, 77.12 degrees E) by using minimal number of commercially available off-the-shelf components. Neodymium Yttrium Aluminum Garnet (Nd:YAG) laser operating at 1064nm with variable pulse energies between 25 and 400 mJ with 10 Hz repetition rate and 7ns pulse duration is used as a transmitter and off axis CASSEGRAIN telescope with 100mm diameter as a receiver. Silicon avalanche photodiode (Si-APD) module with built-in preamplifier and front-end optics is used as detector. This system has been developed for the studies of lower tropospheric aerosols and clouds. Some experiments have been conducted using this set up and preliminary results are discussed. The characteristics of backscattered signals for various transmitter pulse energies are also studied. Atmospheric aerosol extinction coefficient values are calculated using Klett lidar inversion algorithm. The extinction coefficient, in general, falls with range in the lower troposphere and the values lie typically in the range 7.5*10( 5) m(-1) to 1.12*10(-4) m(-1) in the absence of any cloud whereas this value shoots maximum up to 1.267*10(-3) m(-1) (peak extinction) in the presence of clouds. PMID- 21975047 TI - Vibrational spectroscopy of synthetic stercorite H(NH4)Na(PO4).4H2O--a comparison with the natural cave mineral. AB - In order to mimic the chemical reactions in cave systems, the analogue of the mineral stercorite H(NH(4))Na(PO(4)).4H(2)O has been synthesised. X-ray diffraction of the stercorite analogue matches the stercorite reference pattern. A comparison is made with the vibrational spectra of synthetic stercorite analogue and the natural Cave mineral. The mineral in nature is formed by the reaction of bat guano chemicals on calcite substrates. A single Raman band at 920 cm(-1) (Cave) and 922 cm(-1) (synthesised) defines the presence of hydrogen phosphate in the mineral. In the synthetic stercorite analogue, additional bands are observed and are attributed to the dihydrogen and phosphate anions. The vibrational spectra of synthetic stercorite only partly match that of the natural stercorite. It is suggested that natural stercorite is more pure than that of synthesised stercorite. Antisymmetric stretching bands are observed in the infrared spectrum at 1052, 1097, 1135 and 1173 cm(-1). Raman spectroscopy shows the stercorite mineral is based upon the hydrogen phosphate anion and not the phosphate anion. Raman and infrared bands are found and assigned to PO(4)(3-), H(2)O, OH and NH stretching vibrations. Raman spectroscopy shows the synthetic analogue is similar to the natural mineral. A mechanism for the formation of stercorite is provided. PMID- 21975048 TI - Desorption electrospray ionization then MALDI mass spectrometry imaging of lipid and protein distributions in single tissue sections. AB - Imaging mass spectrometry (MS) is a powerful technique for mapping the spatial distributions of a wide range of chemical compounds simultaneously from a tissue section. Co-localization of the distribution of individual molecular species, including particular lipids and proteins, and correlation with the morphological features of a single tissue section are highly desirable for comprehensive tissue analysis and disease diagnosis. We now report on the use, in turn, of desorption electrospray ionization (DESI), matrix assisted laser desorption ionization (MALDI), and then optical microscopy to image lipid and protein distributions in a single tissue section. This is possible through the use of histologically compatible DESI solvent systems, which allow for sequential analyses of the same section by DESI then MALDI. Hematoxylin and eosin (H&E) staining was performed on the same section after removal of the MALDI matrix. This workflow allowed chemical information to be unambiguously matched to histological features in mouse brain tissue sections. The lipid sulfatide (24:1), detected at m/z 888.8 by DESI imaging, was colocalized with the protein MBP isoform 8, detected at m/z 14117 by MALDI imaging, in regions corresponding to the corpus callosum substructure of the mouse brain, as confirmed in the H&E images. Correlation of lipid and protein distributions with histopathological features was also achieved for human brain cancer samples. Higher tumor cell density was observed in regions demonstrating higher relative abundances of oleic acid, detected by DESI imaging at m/z 281.4, and the protein calcyclin, detected by MALDI at m/z 10085, for a human glioma sample. Since correlation between molecular signatures and disease state can be achieved, we expect that this methodology will significantly enhance the value of MS imaging in molecular pathology for diagnosis. PMID- 21975050 TI - Revival of "unsuccessful" chemotherapeutics for highly glycolytic cancers? PMID- 21975049 TI - HNF1alpha inhibition triggers epithelial-mesenchymal transition in human liver cancer cell lines. AB - BACKGROUND: Hepatocyte Nuclear Factor 1alpha (HNF1alpha) is an atypical homeodomain-containing transcription factor that transactivates liver-specific genes including albumin, alpha-1-antitrypsin and alpha- and beta-fibrinogen. Biallelic inactivating mutations of HNF1A have been frequently identified in hepatocellular adenomas (HCA), rare benign liver tumors usually developed in women under oral contraceptives, and in rare cases of hepatocellular carcinomas developed in non-cirrhotic liver. HNF1alpha-mutated HCA (H-HCA) are characterized by a marked steatosis and show activation of glycolysis, lipogenesis, translational machinery and mTOR pathway. We studied the consequences of HNF1alpha silencing in hepatic cell lines, HepG2 and Hep3B and we reproduced most of the deregulations identified in H-HCA. METHODS: We transfected hepatoma cell lines HepG2 and Hep3B with siRNA targeting HNF1alpha and obtained a strong inhibition of HNF1alpha expression. We then looked at the phenotypic changes by microscopy and studied changes in gene expression using qRT-PCR and Western Blot. RESULTS: Hepatocytes transfected with HNF1alpha siRNA underwent severe phenotypic changes with loss of cell-cell contacts and development of migration structures. In HNF1alpha-inhibited cells, hepatocyte and epithelial markers were diminished and mesenchymal markers were over-expressed. This epithelial-mesenchymal transition (EMT) was related to the up regulation of several EMT transcription factors, in particular SNAIL and SLUG. We also found an overexpression of TGFbeta1, an EMT initiator, in both cells transfected with HNF1alpha siRNA and H HCA. Moreover, TGFbeta1 expression is strongly correlated to HNF1alpha expression in cell models, suggesting regulation of TGFbeta1 expression by HNF1alpha. CONCLUSION: Our results suggest that HNF1alpha is not only important for hepatocyte differentiation, but has also a role in the maintenance of epithelial phenotype in hepatocytes. PMID- 21975051 TI - Virus interference. Did rhinoviruses activity hamper the progress of the 2009 influenza A (H1N1) pandemic in Norway? AB - During summer and autumn 2009 Norway, like several other European countries, experienced an unexpected delay in the progress of the 2009 pandemic influenza A (H1N1) virus. It is considered whether interference with other respiratory viruses, in particular rhinoviruses, may have hampered the development of the influenza pandemic, and if interference phenomena are common in the development of outbreaks with epidemic viruses. If so, cytokines, in particular interferon, are the most probable executor of this effect. PMID- 21975052 TI - Cardiac MRI in restrictive cardiomyopathy. AB - Restrictive cardiomyopathy (RCM) is a specific group of heart muscle disorders characterized by inadequate ventricular relaxation during diastole. This leads to diastolic dysfunction with relative preservation of systolic function. Although short axis systolic function is usually preserved in RCM, the long axis systolic function may be severely impaired. Confirmation of diagnosis and information regarding aetiology, extent of myocardial damage, and response to treatment requires imaging. Importantly, differentiation from constrictive pericarditis (CCP) is needed, as only the latter is managed surgically. Echocardiography is the initial cardiac imaging technique but cannot reliably suggest a tissue diagnosis; although recent advances, especially tissue Doppler imaging and spectral tracking, have improved its ability to differentiate RCM from CCP. Cardiac catheterization is the reference standard, but is invasive, two dimensional, and does not aid myocardial characterization. Cardiac magnetic resonance (CMR) is a versatile technique providing anatomical, morphological and functional information. In recent years, it has been shown to provide important information regarding disease mechanisms, and also been found useful to guide treatment, assess its outcome and predict patient prognosis. This review describes the CMR features of RCM, appearances in various diseases, its overall role in patient management, and how it compares with other imaging techniques. PMID- 21975053 TI - Assessment of Japanese iodine intake based on seaweed consumption in Japan: A literature-based analysis. AB - Japanese iodine intake from edible seaweeds is amongst the highest in the world. Predicting the type and amount of seaweed the Japanese consume is difficult due to day-to-day meal variation and dietary differences between generations and regions. In addition, iodine content varies considerably between seaweed species, with cooking and/or processing having an influence on iodine content. Due to all these factors, researchers frequently overestimate, or underestimate, Japanese iodine intake from seaweeds, which results in misleading and potentially dangerous diet and supplementation recommendations for people aiming to achieve the same health benefits seen by the Japanese. By combining information from dietary records, food surveys, urine iodine analysis (both spot and 24-hour samples) and seaweed iodine content, we estimate that the Japanese iodine intake- largely from seaweeds--averages 1,000-3,000 MUg/day (1-3 mg/day). PMID- 21975054 TI - Immunohistochemical study of arginase 1 and 2 in various tissues of rats. AB - Arginase 1 and arginase 2 catalyze the hydrolysis of arginine to ornithine and urea. The localization of these enzymes was studied in various tissues in Sprague Dawley rats by immunohistochemistry and Western blotting. Western blot analysis showed that both arginase 1 and 2 were differentially expressed in the various organs examined. Arginase 1 was expressed at high levels in the liver, at moderate levels in the pancreas, and at low levels in the cerebrum, cerebellum, spinal cord, stomach, small and large intestines, kidneys, lungs, and spleen. The levels of arginase 2 immunoreactivity were high in the kidneys and pancreas, and moderate in the cerebrum, spinal cord, stomach, small intestine, large intestine, and lungs; the levels were very low in the liver and spleen compared with that in the cerebellum. Immunohistochemical analysis largely confirmed the results of the Western blot analysis. These findings indicate that the levels of arginase 1 and 2 varied among organs, suggesting that the arginase isoforms may play organ specific roles in the urea cycle. PMID- 21975055 TI - Production, characterization and applications of a tetanus toxin specific monoclonal antibody T-62. AB - Tetanus neurotoxin (TeNT) represents a potent toxin that binds to its receptors on neurons and inhibits the release of neurotransmitters. Additionally, its fragments are used to transport pharmacological substances to neuronal cell bodies. The main objective of this study was the development of a suitable model system to study internalization of the TeNT. We have produced a monoclonal antibody (MoAb) specific for TeNT by hybridoma technology, after immunization of BALB/c mice with tetanus toxoid, and have named it T-62. The immunochemical characteristics of MoAb T-62 were tested using ELISA, PAGE and immunoblotting. Finally, we have used an immunohistochemical method to detect specific binding of MoAb T-62 to TeNT bound to PC 12 cells. Our results show that MoAb T-62 is highly specific for TeNT, even when it is bound to its receptor, and that it could be of considerable importance in studies regarding fundamental research on TeNT receptors, intracellular transport of TeNT, as well as retrograde transport of pharmaceutical substances and non-invasive delivery of polypeptides through the blood brain barrier. In addition, MoAb T-62 is an invaluable tool in TeNT vaccine production as it can be used for the detection of reverse toxicity, which could drastically reduce the need to use animals in these experiments. PMID- 21975057 TI - "I couldn't do this with opposition from my colleagues": a qualitative study of physicians' experiences as clinical tutors. AB - BACKGROUND: Clinical contact in the early curriculum and workplace learning with active tutorship are important parts of modern medical education. In a previously published study, we found that medical students' tutors experienced a heavier workload, less reasonable demands and less encouragement, than students. The aim of this interview study was to further illuminate physicians' experiences as clinical tutors. METHODS: Twelve tutors in the Early Professional Contact course were interviewed. In the explorative interviews, they were asked to reflect upon their experiences of working as tutors in this course. Systematic text condensation was used as the analysis method. RESULTS: In the analysis, five main themes of physicians' experiences as clinical tutors in the medical education emerged: (a) Pleasure and stimulation. Informants appreciated tutorship and meeting both students and fellow tutors, (b) Disappointment and stagnation. Occasionally, tutors were frustrated and expressed negative feelings, (c) Demands and duty. Informants articulated an ambition to give students their best; a desire to provide better medical education but also a duty to meet demands of the course management, (d) Impact of workplace relations. Tutoring was made easier when the clinic's management provided active support and colleagues accepted students at the clinic, and (e) Multitasking difficulties. Combining several duties with those of a tutorship was often reported as difficult. CONCLUSIONS: It is important that tutors' tasks are given adequate time, support and preparation. Accordingly, it appears highly important to avoid multitasking and too heavy a workload among tutors in order to facilitate tutoring. A crucial factor is acceptance and active organizational support from the clinic's management. This implies that tutoring by workplace learning in medical education should play an integrated and accepted role in the healthcare system. PMID- 21975058 TI - Changes in thrombin generation, fibrinolysis, platelet and endothelial cell activity, and inflammation following endovascular abdominal aortic aneurysm repair. AB - BACKGROUND: Abdominal aortic aneurysm (AAA) is a chronic inflammatory condition associated with a prothrombotic, hypofibrinolytic diathesis that may increase the risk of cardiovascular events. The effect of endovascular aneurysm repair (EVAR) on this prothrombotic diathesis is not fully understood, especially over the medium and long term. A better understanding of these postintervention changes may improve the risk of cardiovascular complications in the long term. The purpose of this study was to examine thrombin generation, fibrinolysis, platelet and endothelial activation, and the inflammatory response during the 12 months following EVAR. METHODS: Twenty-nine patients (mean age, 76.9 years) undergoing EVAR for AAA (mean diameter 6.9 cm) had prothrombin fragment (PF) 1 + 2, thrombin antithrombin complex (TAT), plasminogen activator inhibitor (PAI) activity, tissue plasminogen activator (t-PA) activity and antigen, soluble P- and E selectin, and highly sensitive C-reactive protein (hsCRP) measured before and at 24 hours, and 1, 6, and 12 months after surgery. RESULTS: PF1 + 2 were markedly elevated prior to EVAR and remained so at 24 hours and 1 month, but had decreased significantly at 6 and 12 months. TAT was also elevated prior to EVAR and increased still further by 24 hours, but fell to below baseline levels thereafter. PAI activity and t-PA antigen were normal prior to EVAR, increased significantly at 24 hours, and then fell to baseline levels. t-PA activity was only detectable at 1 and 6 months; there was a significant rise in soluble P- and E-selectin after EVAR, which was sustained for 12 months. hsCRP increased transiently in response to EVAR but returned to preoperative levels by 1 month. CONCLUSIONS: The prothrombotic, hypofibrinolytic diathesis associated with AAA is normalized 12 months after EVAR. This beneficial systemic effect of EVAR for AAA disease may help protect patients against future thromboembolic cardiovascular events. PMID- 21975059 TI - Early diagnosis and resection of an asymptomatic leiomyosarcoma of the inferior vena cava prior to caval obstruction. AB - Leiomyosarcoma of the inferior vena cava is a rare and aggressive tumor, characterized by a slow growth and usually late diagnosis. The mainstay of therapy is surgical resection with limited role for chemotherapy or radiotherapy; resection modalities and the need for caval reconstruction are still matters of debate. In this case report, we describe an asymptomatic intraluminal leiomyosarcoma of the inferior vena cava diagnosed incidentally prior to caval occlusion during a routine ultrasound examination of the upper abdomen. PMID- 21975060 TI - Nonsurgical treatment of scalp arteriovenous malformation using a combination of ultrasound-guided thrombin injection and transarterial coil embolization. AB - Scalp arteriovenous malformations are treated by surgical excision in many patients. We report a patient with a scalp arteriovenous malformation who was successfully treated by a combination of ultrasound-guided thrombin injection (UGTI) and transarterial coil embolization. This patient was a 52-year-old man with a subcutaneous mass in the left retroauricular region. An angiogram showed that the mass was a nidus of arteriovenous malformation. We performed UGTI after transarterial coil embolization. No recurrence or complication was reported during 2 years of follow-up. This report describes the advantages of UGTI and the method for complete occlusion of the collateral artery. PMID- 21975061 TI - The natural history of duplex-detected stenosis after femoropopliteal endovascular therapy suggests questionable clinical utility of routine duplex surveillance. AB - OBJECTIVE: Duplex ultrasound (DU) surveillance (DUS) criteria for vein graft stenosis and thresholds for reintervention are well established. The natural history of DU-detected stenosis and the threshold criteria for reintervention in patients undergoing endovascular therapy (EVT) of the femoropopliteal system have yet to be determined. We report an analysis of routine DUS after infrainguinal EVT. METHODS: Consecutive patients undergoing EVT of the superficial femoral artery (SFA) or popliteal artery were prospectively enrolled in a DUS protocol (<=1 week after intervention, then at 3, 6, and 12 months thereafter). Peak systolic velocity (PSV) and velocity ratio (Vr) were used to categorize the treated artery: normal was PSV <200 cm/s and Vr <2, moderate stenosis was PSV = 200-300 cm/s or Vr = 2-3, and severe stenosis was PSV >300 cm/s or Vr >3. Reinterventions were generally performed for persistent or recurrent symptoms, allowing us to analyze the natural history of DU-detected lesions and to perform sensitivity and specificity analysis for DUS criteria predictive of failure. RESULTS: Ninety-four limbs (85 patients) underwent EVT for SFA-popliteal disease and were prospectively enrolled in a DUS protocol. The initial scans were normal in 61 limbs (65%), and serial DU results remained normal in 38 (62%). In 17 limbs (28%), progressive stenoses were detected during surveillance. The rate of thrombosis in this subgroup was 10%. Moderate stenoses were detected in 28 (30%) limbs at initial scans; of these, 39% resolved or stabilized, 47% progressed to severe, and occlusions developed in 14%. Five (5%) limbs harbored severe stenoses on initial scans, and 80% of lesions resolved or stabilized. Progression to occlusion occurred in one limb (20%). The last DUS showed 25 limbs harbored severe stenoses; of these, 13 (52%) were in symptomatic patients and thus required reintervention regardless of DU findings. Eleven limbs (11%) eventually occluded. Sensitivity and specificity of DUS to predict occlusion were 88% and 60%, respectively. CONCLUSIONS: DUS does not reliably predict arterial occlusion after EVT. Stenosis after EVT appears to have a different natural history than restenosis after vein graft bypass. EVT patients are more likely to have severe stenosis when they present with recurrent symptoms, in contrast to vein graft patients, who commonly have occluded grafts when they present with recurrent symptoms. The potential impact of routine DU-directed reintervention in patients after EVT is questionable. The natural history of DU-detected stenosis after femoropopliteal endovascular therapy suggests questionable clinical utility of routine DUS. PMID- 21975062 TI - Inferior vena cava graft-enteric fistula after extended hepatectomy with caval replacement. AB - A case of an inferior vena cava (IVC) graft-enteric fistula manifesting with recurrent sepsis 11 years after a right hepatectomy extending to segments I and IV, the extrahepatic bile duct, and IVC followed by chemotherapy and external beam radiation therapy is described. A preoperative workup revealed graft thrombosis with air bubbles inside the lumen. Laparotomy found a chronic fistula between the graft and the enteric biliary loop. Removal of the graft without further vascular reconstruction, a take-down of the biliary loop, and a redo hepaticojejunostomy were performed successfully. The diagnostic challenges, possible etiology, and therapeutic implications of this case are discussed. PMID- 21975063 TI - Clinical analysis of the corona phlebectatica. AB - BACKGROUND: The corona phlebectatica (CP) is classically described as the presence of abnormally visible cutaneous blood vessels at the ankle with four components: "venous cups," blue and red telangiectases, and capillary "stasis spots." Previous studies showed that the presence of CP is strongly related to the clinical severity of chronic venous disorders (CVD) and the presence of incompetent leg perforators. The aim of this study was to select the most informative components of the CP in the assessment of the clinical severity of CVD patients. METHODS: A multicentric series of 262 unselected patients (524 limbs) consulted for CVD were clinically evaluated using a standardized form to record the CEAP "C" items and the presence of the four CP components. Standard categorical and ordinal statistics were used to describe the external validity of the CP components as severity indexes, taking the "C" classes as reference. RESULTS: "Stasis spots" (P < .001; r = .44) and blue telangiectases (P < .01; r = .32) were linearly associated with the ascending order of "C" classes, whereas the relationship is less clear for the red telangiectases and the "venous cups." The association pattern of the four components showed that only the blue telangiectases and the "stasis spots" were consistent with each other. Blue telangiectases were found more sensitive (0.91 vs 0.75) but less specific (0.52 vs 0.80) than "stasis spots" for advanced venous insufficiency (CEAP "C4-6"). CONCLUSION: This study shows that only blue telangiectases and "stasis spots" provide valuable information in patients with CVD and deserve to be taken into account in the evaluation of such patients. Further studies are needed to show the reproducibility of this data, which we regard as essential for clinical use. PMID- 21975065 TI - Synthesis and characterization of [125I]2-iodo N-[(S)-{(S)-1-methylpiperidin-2 yl}(phenyl)methyl]3-trifluoromethyl-benzamide as novel imaging probe for glycine transporter 1. AB - In this study, 2-iodo substituted 1-methylpiperidin-2-yl benzamide derivatives were synthesized and evaluated as candidate SPECT imaging agents for glycine transporter 1 (GlyT1). In JAR cells, which predominantly express GlyT1, 2-iodo N [(S)-{(S)-1-methylpiperidin-2-yl}(phenyl)methyl]3-trifluoromethyl-benzamide (5) showed excellent inhibitory activity of [(3)H]glycine uptake (IC(50)=2.4 nM). Saturation assay in rat cortical membranes revealed that [(125)I]5 had a single high affinity binding site with a K(d) of 1.54 nM and a B(max) of 3.40 pmol/mg protein. In vitro autoradiography demonstrated that [(125)I]5 showed consistent accumulation with GlyT1 expression. The in vitro binding was greatly inhibited by GlyT1 inhibitors but not by other site ligands, which suggested the high specific binding of [(125)I]5 with GlyT1. In the biodistribution and ex vivo autoradiography studies using mice, [(125)I]5 showed high blood-brain barrier permeability (1.68-2.17% dose/g at 15-60 min) and similar regional brain distribution pattern with in vitro results. In addition, pre-treatment of GlyT1 ligands resulted in significant decrease of [(125)I]5 binding in the GlyT1-rich regions. This preliminary study demonstrated that radio-iodinated 5 is a promising SPECT imaging probe for GlyT1. PMID- 21975064 TI - Delayed inflammatory mRNA and protein expression after spinal cord injury. AB - BACKGROUND: Spinal cord injury (SCI) induces secondary tissue damage that is associated with inflammation. We have previously demonstrated that inflammation related gene expression after SCI occurs in two waves - an initial cluster that is acutely and transiently up-regulated within 24 hours, and a more delayed cluster that peaks between 72 hours and 7 days. Here we extend the microarray analysis of these gene clusters up to 6 months post-SCI. METHODS: Adult male rats were subjected to mild, moderate or severe spinal cord contusion injury at T9 using a well-characterized weight-drop model. Tissue from the lesion epicenter was obtained 4 hours, 24 hours, 7 days, 28 days, 3 months or 6 months post-injury and processed for microarray analysis and protein expression. RESULTS: Anchor gene analysis using C1qB revealed a cluster of genes that showed elevated expression through 6 months post-injury, including galectin-3, p22PHOX, gp91PHOX, CD53 and progranulin. The expression of these genes occurred primarily in microglia/macrophage cells and was confirmed at the protein level using both immunohistochemistry and western blotting. As p22PHOX and gp91PHOX are components of the NADPH oxidase enzyme, enzymatic activity and its role in SCI were assessed and NADPH oxidase activity was found to be significantly up-regulated through 6 months post-injury. Further, treating rats with the nonspecific, irreversible NADPH oxidase inhibitor diphenylene iodinium (DPI) reduced both lesion volume and expression of chronic gene cluster proteins one month after trauma. CONCLUSIONS: These data demonstrate that inflammation-related genes are chronically up regulated after SCI and may contribute to further tissue loss. PMID- 21975066 TI - Formulating a new basis for the treatment against botulinum neurotoxin intoxication: 3,4-Diaminopyridine prodrug design and characterization. AB - Botulism is a disease characterized by neuromuscular paralysis and is produced from botulinum neurotoxins (BoNTs) found within the Gram positive bacterium Clostridium botulinum. This bacteria produces the most deadliest toxin known, with lethal doses as low as 1 ng/kg. Due to the relative ease of production and transport, the use of these agents as potential bioterrorist weapons has become of utmost concern. No small molecule therapies against BoNT intoxication have been approved to date. However, 3,4-diaminopyridine (3,4-DAP), a potent reversible inhibitor of voltage-gated potassium channels, is an effective cholinergic agonist used in the treatment of neuromuscular degenerative disorders that require cholinergic enhancement. 3,4-DAP has also been shown to facilitate recovery of neuromuscular action potential post botulinum intoxication by blocking K(+) channels. Unfortunately, 3,4-DAP displays toxicity largely due to blood-brain-barrier (BBB) penetration. As a dual-action prodrug approach to cholinergic enhancement we have designed carbamate and amide conjugates of 3,4 DAP. The carbamate prodrug is intended to be a slowly reversible inhibitor of acetylcholinesterase (AChE) along the lines of the stigmines thereby allowing increased persistence of released acetylcholine within the synaptic cleft. As a secondary activity, cleavage of the carbamate prodrug by AChE will afford the localized release of 3,4-DAP, which in turn, will enhance the pre-synaptic release of additional acetylcholine. Being a competitive inhibitor with respect to acetylcholine, the activity of the prodrug will be greatest at the synaptic junctions most depleted of acetylcholine. Here we report upon the synthesis and biochemical characterization of three new classes of prodrugs intended to limit previously reported stability and toxicity issues. Of the prodrugs examined, compound 32, demonstrated the most clinically relevant half-life of 2.76 h, while selectively inhibiting AChE over butyrylcholinesterase--a plasma-based high activity esterase. Future in vivo studies could provide validation of prodrug 32 as a potential treatment against BoNT intoxication as well as other neuromuscular disorders. PMID- 21975067 TI - Binding of isoxazole and pyrazole derivatives of curcumin with the activator binding domain of novel protein kinase C. AB - The protein kinase C (PKC) family of serine/threonine kinases is an attractive drug target because of its involvement in the regulation of various cellular functions, including cell growth, differentiation, metabolism, and apoptosis. The endogenous PKC activator diacylglycerol contains two long carbon chains, which are attached to the glycerol moiety via ester linkage. Natural product curcumin (1), the active constituent of Curcuma L., contains two carbonyl and two hydroxyl groups. It modulates PKC activity and binds to the activator binding site (Majhi et al., Bioorg. Med. Chem.2010, 18, 1591). To investigate the role of the carbonyl and hydroxyl groups of curcumin in PKC binding and to develop curcumin derivatives as effective PKC modulators, we synthesized several isoxazole and pyrazole derivatives of curcumin (2-6), characterized their absorption and fluorescence properties, and studied their interaction with the activator-binding second cysteine-rich C1B subdomain of PKCdelta, PKCepsilon and PKCtheta. The EC(50)s of the curcumin derivatives for protein fluorescence quenching varied in the range of 3-25 MUM. All the derivatives showed higher binding with the PKCthetaC1B compared with PKCdeltaC1B and PKCepsilonC1B. Fluorescence emission maxima of 2-5 were blue shifted in the presence of the C1B domains, confirming their binding to the protein. Molecular docking revealed that hydroxyl, carbonyl and pyrazole ring of curcumin (1), pyrazole (2), and isoxazole (4) derivatives form hydrogen bonds with the protein residues. The present result shows that isoxazole and pyrazole derivatives bind to the activator binding site of novel PKCs and both carbonyl and hydroxy groups of curcumin play roles in the binding process, depending on the nature of curcumin derivative and the PKC isotype used. PMID- 21975068 TI - Chemical synthesis, biological evaluation and structure-activity relationship analysis of azaisoindolinones, a novel class of direct enoyl-ACP reductase inhibitors as potential antimycobacterial agents. AB - The synthesis and biological evaluation of azaisoindolinone compounds embedding a lipophilic chain on the framework were performed. These compounds were designed as InhA inhibitors and as anti-Mycobacterium tuberculosis agents. Structure activity relationships concerning the length and the location of the lipophilic chain around the azaisoindolinone framework, the suppression of the phenyl group, the bioisosteric substitution of ether link and alkylating of the tertiary hydroxyl and the hemiamidal nitrogen were also investigated, revealing insightful information and thereby enabling further diversification of the azaisoindolinone scaffold for new antitubercular agents. PMID- 21975069 TI - Melanin-concentrating hormone receptor 1 antagonists: synthesis, structure activity relationship, docking studies, and biological evaluation of 2,3,4,5 tetrahydro-1H-3-benzazepine derivatives. AB - Melanin-concentrating hormone receptor 1 (MCHR1) antagonists have been studied as potential agents for the treatment of obesity. Initial structure-activity relationship studies of in-house hit compound 1a and subsequent optimization studies resulted in the identification of tetrahydroisoquinoline derivative 23, 1 (2-acetyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-[4-(4-chlorophenyl)piperidin-1 yl]butan-1-one, as a potent hMCHR1 antagonist. A homology model of hMCHR1 suggests that these compounds interact with Asn 294 and Asp 123 in the binding site of hMCHR1 to enhance binding affinity. Oral administration of compound 23 dose-dependently reduced food intake in diet-induced obesity (DIO)-F344 rats. PMID- 21975070 TI - Defining the optimal dose of radiation in leukemic patients with extramedullary lesions. AB - BACKGROUND: Analysis of the clinical response of extramedullary lesions in leukemic patients treated with radiation therapy (RT) and defining the optimal dose of radiation. METHODS: Forty-two extramedullary lesions found in 24 leukemic patients treated with RT were reviewed. The radiation was delivered usually 2 Gy/day, up to a median of 20 Gy (range: 18.0-40.8). The clinical response and symptom palliation effect were analyzed. The factors affecting the response were also included in the analysis. RESULTS: After a median time of 7.9 weeks, the overall response rate was 76.2%. A complete response (CR) was achieved in 35.7%, a partial response in 40.5%. The symptom was relieved in 85.7% sites. The overall response rate was better in patients whose initial tumor size was smaller than 10 cm2 (p = 0.010) or who were treated with more than 25 Gy (p = 0.031). The overall CR rate was also higher in those who had smaller tumors (smaller than 6 cm or 30 cm2) (p = 0.015), or when the tumor was located in soft tissue (p = 0.029). CONCLUSIONS: Extramedullary lesions in leukemic patients can be successfully treated with RT. The tumor response rate was excellent and symptom relief was achieved in almost all patients. There was a better response to treatment when the tumor was small or it was located in soft tissue. Although, there was no definite correlation between volume reduction and total dose, it seems that higher total dose more of than 25 Gy is needed for better response. PMID- 21975071 TI - Outbreak of equine herpesvirus myeloencephalopathy in France: a clinical and molecular investigation. AB - Equid herpesvirus 1 (EHV-1)-associated myeloencephalopathy (EHM) is a disease affecting the central nervous system of horses. Despite the constantly increasing interest about this syndrome, epidemiological data are limited especially when related to the description of large outbreaks. The aim of this article is to describe clinical, virological and molecular data obtained throughout a severe outbreak of EHM, with emphasis on laboratory diagnostic methods. The epidemic disease concerned a riding school in France where 7/66 horses aged 12-22 years developed signs of neurological disease in July 2009. Diagnosis of EHM was supported by EHV-1 detection using both real-time PCR and virus culture, and SNP PCR test for viral strain characterization. EHM morbidity was 10.6% (7/66), mortality was 7.5% (5/66) and case fatality rate was 71.4% (5/7). Clinical presentation of the disease was characterized by the fact that fever was systematically present within 2 days before the severe neurological signs were noted. EHV-1 was detected by PCR in each available blood and nasal swab samples. Neuropathogenic strain only (G(2254) ) was isolated during the current outbreak; C(t) values, used as an indicative level of the viral load, ranged 26.0-37.0 among the six sampled horses. The amount of virus in biological samples was not systematically related to the intensity of the clinical signs being observed. In conclusion, this article described a severe outbreak of EHM while limited in time and restricted to one premise. Molecular data strongly suggested taking into account any low viral load as being a potential risk factor for neurological manifestations. PMID- 21975072 TI - Classification of extensively damaged teeth to evaluate prognosis. AB - The restoration of teeth with extensive structural damage is an important clinical procedure in dental practice. However, despite the availability of a variety of materials, techniques and studies in the scientific literature, the criteria for selection of such teeth for restoration need clarification. The approach to severely compromised teeth should be based on consistent scientific evidence to reduce dental error and improve the prognosis. If restoration is indicated, it must conserve and protect the remaining tooth structure. In this article, we develop and suggest clinical criteria and guidelines that clinicians may use to identify and classify extensively damaged teeth to help in the diagnosis, treatment plan and prognosis. PMID- 21975073 TI - Toward safer care: reporting systems, checklists and process standardization. PMID- 21975074 TI - Metabolic syndrome and oral markers of cardiometabolic risk. AB - Metabolic syndrome is associated with increased risk of cardiovascular disease and type 2 diabetes mellitus. However, clinical diagnosis of metabolic syndrome alone does not permit proper assessment of cardiometabolic risk. Instead, it should be viewed as a modifiable risk factor. The development and progression of metabolic syndrome may be the result of many elements, with visceral obesity as a central component. Both metabolic syndrome and visceral obesity are linked to chronic inflammation, which leads to atherosclerosis and, thus, increases cardiometabolic risk. Obesity has been related to caries, traumatic injury, hyposalivation, tooth loss and periodontal diseases, and the latter have been associated with almost every feature of atherosclerosis. Thus, severe or refractory periodontal disease or a significant loss of teeth could serve as markers of cardiometabolic risk. Finally, there is growing evidence that saliva can reflect virtually the entire spectrum of normal and disease states; thus, we are likely to see increased use of saliva as a diagnostic tool and consequently, dentists may have a greater involvement in the identification and monitoring of non-oral disorders. PMID- 21975075 TI - Let's build a treasure together. PMID- 21975076 TI - Primary HIV-1 drug resistance in the C-terminal domains of viral reverse transcriptase among drug-naive patients from Southern Brazil. AB - BACKGROUND: Major and accessory drug resistance mutations have been recently characterized in the C-terminal RT subdomains of HIV-1, connection and RNase H. However, their presence in treatment-naive patients infected with HIV-1 non-B subtypes remains largely unknown. OBJECTIVES: To characterize the patterns of primary resistance at the C-terminal RT subdomains of HIV-1 infecting subjects in the southern region of Brazil, where HIV-1 subtypes B and C co-circulate. STUDY DESIGN: Plasma viral RNA was extracted from patients recently diagnosed for HIV infection (2005-2008). The protease and reverse transcriptase regions were PCR amplified and sequenced. Infecting HIV subtypes were assigned by phylogenetic inference and drug resistance mutations were determined following the IAS consensus and recent reports on C-terminal RT mutations. RESULTS: The major mutation to NNRTI T369I/V was found in 1.8% of patients, while A376S was present in another 8.3%. In the RNase H domain, the compensatory mutation D488E was more frequently observed in subtype C than in subtype B (p=0.038), while the inverse was observed for mutation Q547K (p<0.001). The calculated codon genetic barrier showed that 22% of subtype B isolates, but no subtype C, carried T360, requiring two transitions to change into the resistance mutation 360V. CONCLUSIONS: Major resistance-conferring mutations to NNRTI were detected in 10% of RT connection domain viral sequences from treatment-naive subjects. We showed for the first time that the presence of specific polymorphisms can constrain the acquisition of definite resistance mutations in the connection and RNase H subdomains of HIV-1 RT. PMID- 21975077 TI - Mumps virus diagnosis and genotyping using a novel single RT-PCR. AB - BACKGROUND: IgM detection is considered as the gold standard for mumps diagnosis. Currently, most cases in developed countries occur in highly vaccinated populations due to secondary vaccine failure. In these patients, pre-existing vaccine-induced antibodies are not able to neutralise the virus, but prevent the typical primary response, so that specific IgM is not always elicited. Consequently, acute infection has to be demonstrated by direct detection of the virus by viral isolation or genomic amplification. RT-PCR allows a diagnosis with the maximum sensitivity to be made and also forms the basis for genotype characterisation by sequencing the SH gene, according to WHO recommendations. However, none of the RT-PCR techniques properly evaluated for the diagnosis of acute mumps infection yields an amplification fragment useful for genotyping, and none of the amplification techniques described for genotyping has proved to be sensitive enough for diagnosis. OBJECTIVES: Development of a RT-PCR for the mumps virus diagnosis and genotyping, properly evaluated in comparison with serological gold-standard technique. STUDY DESIGN: 195 suspected mumps cases and six wild type MuV genotypes were studied. RESULTS: Our method was able to detect 0.001 TCID(50) of mumps virus. Fifty-eight of these showed positive results, of which 54 (93.3%) showed mumps RNA in saliva, while only 20 (34.5%) had mumps IgM in serum. Genotypes G1, G2, H1, H2, D1 and C were identified in positive samples. CONCLUSIONS: The technique described could be a very useful tool for mumps surveillance, management and control. PMID- 21975078 TI - Detection and verification of glycosylation patterns of glycoproteins from clinical specimens using lectin microarrays and lectin-based immunosorbent assays. AB - Aberrant glycosylation is a fundamental characteristic of progression of diseases such as cancer. Therefore, characterization of glycosylation patterns of proteins from disease tissues may identify changes specific to the disease development and improve diagnostic performance. Thus, analysis strategies with sufficient sensitivity for evaluation of glycosylation patterns in clinical specimens are needed. Here, we describe an analytical strategy for detection and verification of glycosylation patterns. It is based on a two-phase platform including a pattern discovery phase to identify the glycosylation changes using high-density lectin microarrays and a verification phase by developing lectin-based immunosorbent assays using the identified lectins. We evaluated the analytical performance of the platform using the glycoprotein standard and found that the lectin microarray could detect specific bindings of glycoprotein to lectins at the nanogram level and the lectin-based immunosorbent assay could be used for verification of protein glycosylation. We then applied the approach to the analysis of glycosylation patterns of two glycoproteins, which are highly expressed in prostate cancer in our prior studies, prostate specific antigen (PSA) and membrane metallo-endopeptidase (MME), from aggressive (AC) and nonaggressive prostate cancer (NAC) tissues. The observed differences in glycosylation patterns of PSA and MME may represent a significant clinical importance and could be used to develop multiplex assays for diagnosis of aggressive prostate cancer. PMID- 21975079 TI - Arrow-elicited cueing effects at short intervals: Rapid attentional orienting or cue-target stimulus conflict? AB - The observation of cueing effects (faster responses for cued than uncued targets) rapidly following centrally-presented arrows has led to the suggestion that arrows trigger rapid automatic shifts of spatial attention. However, these effects have primarily been observed during easy target-detection tasks when both cue and target remain on the screen until the behavioral response. We manipulated stimulus duration and task difficulty in an attention-cueing experiment to explore non-attentional explanations for rapid cueing effects. Contrary to attention-based predictions, short-interval cueing effects were observed only for long-duration cue and target stimuli, occurred even when the cue and target were presented simultaneously, and were driven by slowing of the uncued-target responses, rather than any facilitation for cued targets. We propose that, under these long-duration, short-interval conditions, the processing of the cue and target interact more extensively in the brain, and that when the cue and target convey incongruent spatial information (i.e., on invalidly cued trials) it leads to conflict-related slowing of responses. PMID- 21975080 TI - Glycyrrhiza glabra protects from myocardial ischemia-reperfusion injury by improving hemodynamic, biochemical, histopathological and ventricular function. AB - Present study evaluated the cardioprotective effect of Glycyrrhiza glabra against ischemia-reperfusion injury (I-R) induced by ligation of left anterior descending coronary artery (LADCA) in rats. Ligation of LADCA for 45 min followed by 60 min of reperfusion has induced significant (p<0.05) heart dysfunction evidenced by significant (p<0.05) decrease in mean arterial pressure (MAP), heart rate (HR), contractility; (+)LVdP/dtmax and relaxation; (-)LVdP/dtmax along with increased left ventricular end diastolic pressure (LVEDP). Ligation induced I-R injury also significantly (p<0.05) decreased myocyte injury enzymes, creatine phosphokinase MB (CK-MB) isoenzyme and lactate dehydrogenase (LDH) as well as antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). Furthermore, I-R injury also induced lipid peroxidation evidenced by significant (p<0.05) increase in malondialdehyde (MDA) formation and histological perturbations concomitant to depletion of glutathione (GSH) from heart. However, pretreatment with G. glabra significantly (p<0.05) prevented the depletion of the antioxidant enzymes; SOD, CAT, GSH-Px and myocyte injury marker enzymes; CK-MB isoenzyme and LDH. Pretreatment with G. glabra also prevented GSH depletion and inhibited lipid peroxidation in heart. In addition to improving biochemical indices of myocardial function, G. glabra also significantly (p<0.05) reinstated MAP, HR, (+/-)LVdP/dtmax and attenuated abrupt rise in LVEDP. Histopathological preservation evidenced by reduced infiltration of cells and myonecrosis depicted the myocardial salvaging effect of G. glabra. Taken together, results of the present study clearly suggest the cardioprotective potential of G. glabra against myocardial infarction by amelioration of oxidative stress and favorable modulation of cardiac function. PMID- 21975081 TI - [Validation of the Yale Physical Activity Survey in chronic obstructive pulmonary disease patients]. AB - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) perform limited physical activity. Surprisingly, there is a lack of research in COPD about the validity of physical activity questionnaires. Our aim was to validate the Yale Physical Activity Survey in COPD patients in order to quantify and classify their levels of physical activity. METHODS: 172 COPD patients from 8 university hospitals in Spain wore an accelerometer (SenseWear((r))Pro(2)Armband) for 8 days and answered the questionnaire 15 days later. Statistical analyses used to compare both tools measures included: (i) Spearman's correlation coefficient, (ii) intraclass correlation coefficient (ICC) and Bland-Altman plots, (iii) distribution of accelerometer measurements according to tertiles of the questionnaire, and (iv) receiver operating characteristic (ROC) curves to detect sedentary patients. RESULTS: 94% of participants were men, 28% were active smokers and 7% were currently working. Mean (standard deviation) age was 70 (8) years, mean post-bronchodilator FEV(1) was 52 (15)% predicted, and median (p25 p75) steps taken was 5,702 (3,273-9,253) steps per day(-1). Spearman correlations were low to moderate (from 0.29 to 0.52, all P<.001). ICCs showed weak agreement (from 0.34 to 0.40, all P<.001). A wide variability in agreement was observed in the Bland-Altman plots. Significant differences in accelerometer measurements were found according to questionnaire tertiles (all P<.001). The area under the ROC for identifying sedentarism was 0.71 (95% CI: 0.63-0.79). CONCLUSIONS: The Yale Physical Activity Survey may be a valid tool to classify, but not to quantify, physical activity performed by COPD patients. The summary index of this questionnaire, based on seven short questions, shows the best validity properties. This suggests that it should be considered a screening tool to identify patients at risk for sedentarism. PMID- 21975082 TI - A method to evaluate cardiac surgery mortality: phase of care mortality analysis. AB - BACKGROUND: This is a study of a method of mortality review, adopted by the Michigan Society of Thoracic and Cardiovascular Surgeons, to enhance understanding of mortality and potentially avoidable deaths after cardiac surgery, utilizing a voluntary statewide database. METHODS: A system to categorize mortality was developed utilizing a phase of care mortality analysis approach as well as providing criteria to classify mortality as potentially "avoidable." For each mortality, the operating surgeon categorized a cardiac surgery mortality trigger into 1 of 5 time frames: preoperative, intraoperative, intensive care unit (ICU), postoperative floor, and discharge. RESULTS: A total of 53,674 adult cardiac operations were performed from January 1, 2006 to June 30, 2010 with a crude mortality of 3.5% (1,905 of 53,674). Of the mortalities analyzed, 35% (618 of 1,780) were preoperative, 25% (451 of 1,780) were ICU, 19% (333 of 1,780) were intraoperative, 11% (198 of 1,780) were floor, and 10% (180 of 1,780) were discharge phase. "Avoidable" mortality triggers occurred in 53% (174 of 333) of the intraoperative, 41% (253 of 618) and (184 of 451) of the preoperative and ICU phases, 42% (83 of 198) of the floor, and 19% (35 of 180) of the discharge phase. Overall potentially avoidable mortality was 41% (729 of 1780). Thirty-six percent (644 of 1,780) of the mortalities were coronary artery bypass grafting patients and 29% (188 of 644) of these were in the preoperative phase, with a mean predicted risk of 16%. CONCLUSIONS: This analysis identifies the occurrence of potentially avoidable mortalities in the 4 hospital phases of care, with the largest absolute number of avoidable mortalities occurring in the preoperative phase. A focus on these phases of care provides significant opportunity for quality improvement initiatives. Utilizing phase of care mortality analysis stimulates surgeons and hospitals to develop and refine mortality reviews and provides a structured statewide platform for discussion, education, quality improvement, and enhanced outcomes. PMID- 21975083 TI - Generic integration of content-based image retrieval in computer-aided diagnosis. AB - Content-based image retrieval (CBIR) offers approved benefits for computer-aided diagnosis (CAD), but is still not well established in radiological routine yet. An essential factor is the integration gap between CBIR systems and clinical information systems. The international initiative Integrating the Healthcare Enterprise (IHE) aims at improving interoperability of medical computer systems. We took into account deficiencies in IHE compliance of current picture archiving and communication systems (PACS), and developed an intermediate integration scheme based on the IHE post-processing workflow integration profile (PWF) adapted to CBIR in CAD. The Image Retrieval in Medical Applications (IRMA) framework was used to apply our integration scheme exemplarily, resulting in the application called IRMAcon. The novel IRMAcon scheme provides a generic, convenient and reliable integration of CBIR systems into clinical systems and workflows. Based on the IHE PWF and designed to grow at a pace with the IHE compliance of the particular PACS, it provides sustainability and fosters CBIR in CAD. PMID- 21975084 TI - A model to personalize scheduling of complex prescriptions. AB - Medication adherence tends to affect the recovery of patients. Patients having poor medication adherence show a worsening of their condition and/or increased complications. Unfortunately, between 20% and 50% of chronic patients are unable to manage their medications. This study proposes a model to improve the patients' medication compliance by reducing medication frequency. Published studies have shown that, based on the patients' lifestyle, simplification of the medication frequency and remodeling of the medication schedule is able to help improve medication adherence. Therefore, this study tried to simplify medication frequency by combining therapies. Moreover, by adjusting according to lifestyle, the study also tries to remodel medication timing in relation to mealtimes to create personal medication schedules. In this study, we used 19,393,452 outpatient prescriptions from the National Health Insurance Research Database to verify our system (algorithm optimized). At the same time, we examined the differences between the frequency summarized by general public and experts' advice medication behavior. Compared with the experts' advice method, this system has reduced the medication frequency in about 49% of prescriptions. Using combined medication to simplify medication frequency is able to reduce the medication frequency significantly and improve medication adherence. Furthermore, this should also improve patient recovery, reduce drug hazards and result in less drug wastage. PMID- 21975085 TI - Impact of pulmonary vascular stiffness and vasodilator treatment in pediatric pulmonary hypertension: 21 patient-specific fluid-structure interaction studies. AB - Recent clinical studies of pulmonary arterial hypertension (PAH) have found correlations between increased pulmonary vascular stiffness (PVS) and poorer disease outcomes. However, mechanistic questions remain about the relationships amongst PVS, RV power, and vascular hemodynamics in the setting of progressive PAH that are difficult or impossible to answer using direct measurements. Clinically validated patient-specific computational modeling may allow exploration of these issues through perturbation-based predictive testing. Here we use a simple patient-specific model to answer four questions: how do hemodynamics change as PAH worsens? How does increasing PVS impact hemodynamics and RV power? For a patient with moderate PAH, what are the consequences if the pressures increase modestly yet sufficiently to engage collagen in those vessels? What impact does pressure-reducing vasodilator treatment have on hemodynamics? Twenty-one sets of model-predicted impedance and mean PA pressure (mPAP) show good agreement with clinical measurements, thereby validating the model. Worsening was modeled using data from three PAH outcomes groups; these show not only the expected increase in mPAP, but also an increase in pressure pulsatility. Interestingly, chronically increasing mPAP decreased WSS, suggesting that increased PA cross-sectional area affected WSS greater than increased PVS. For a patient with moderately high PVR (12.7 WU) with elastin-based upstream vascular remodeling, moving from elastin-dominant vessel behavior to collagen-dominant behavior caused substantial increases in mPAP, pressure and WSS pulsatility. For the same patient, reducing PVR through a simulated vasodilator to a value equivalent to mild PAH did not decrease pressure pulsatility and dramatically increased WSS pulsatility. Overall, these results suggest a close association between PVS and hemodynamics and that hemodynamics may play an important role in progressing PAH. These support the hypothesis that treatments should target decreasing or reversing upstream vascular remodeling in addition to decreasing mean pressures. PMID- 21975086 TI - Numerical streamline patterns at swimmer's surface using RANS equations. AB - The objective of this article is to perform a numerical modeling on the flow dynamics around a competitive female swimmer during the underwater swimming phase for a velocity of 2.2 m/s corresponding to national swimming levels. Flow around the swimmer is assumed turbulent and simulated with a computational fluid dynamics method based on a volume control approach. The 3D numerical simulations have been carried out with the code ANSYS FLUENT and are presented using the standard k-omega turbulence model for a Reynolds number of 6.4 * 10(6). To validate the streamline patterns produced by the simulation, experiments were performed in the swimming pools of the National Institute of Sports and Physical Education in Paris (INSEP) by using the tufts method. PMID- 21975087 TI - Population genetic structure of Anopheles arabiensis and Anopheles gambiae in a malaria endemic region of southern Tanzania. AB - BACKGROUND: Genetic diversity is a key factor that enables adaptation and persistence of natural populations towards environmental conditions. It is influenced by the interaction of a natural population's dynamics and the environment it inhabits. Anopheles gambiae s.s. and Anopheles arabiensis are the two major and widespread malaria vectors in sub-Saharan Africa. Several studies have examined the ecology and population dynamics of these vectors. Ecological conditions along the Kilombero valley in Tanzania influence the distribution and population density of these two vector species. It remains unclear whether the ecological diversity within the Kilombero valley has affected the population structure of An. gambiae s.l. populations. The goal of this study was to characterise the genetic structure of sympatric An. gambiae s.s and An. arabiensis populations along the Kilombero valley. METHODOLOGY: Mosquitoes were collected from seven locations in Tanzania: six from the Kilombero valley and one outside the valley (-700 km away) as an out-group. To archive a genome-wide coverage, 13 microsatellite markers from chromosomes X, 2 and 3 were used. RESULTS: High levels of genetic differentiation among An. arabiensis populations was observed, as opposed to An. gambiae s.s., which was genetically undifferentiated across the 6,650 km2 of the Kilombero valley landscape. It appears that genetic differentiation is not attributed to physical barriers or distance, but possibly by ecological diversification within the Kilombero valley. Genetic divergence among An. arabiensis populations (FST = 0.066) was higher than that of the well-known M and S forms of An. gambiae s. s. in West and Central Africa (FST = 0.035), suggesting that these populations are maintained by some level of reproductive isolation. CONCLUSION: It was hypothesized that ecological diversification across the valley may be a driving force for observed An. arabiensis genetic divergence. The impact of the observed An. arabiensis substructure to the prospects for new vector control approaches is discussed. PMID- 21975088 TI - Norwegian trauma team leaders--training and experience: a national point prevalence study. AB - BACKGROUND: The treatment of trauma victims is a complex multi-professional task in a stressful environment. We previously found that trauma team members perceive leadership as the most important human factor. The aim of the present study was to assess the experience and education of Norwegian trauma team leaders, and allow them to describe their perceived educational needs. METHODS: We conducted an anonymous descriptive study using a point prevalence methodology based on written questionnaires. All 45 hospitals in Norway receiving severely injured trauma victims were contacted on a randomly selected weeknight during November 2009. Team leaders were asked to specify what trauma related training programs they had participated in, how much experience they had, and what further training they wished, if any. RESULTS: Response rate was 82%. Slightly more than half of the team leaders were residents. The median working experience as a surgeon among team leaders was 7.5 years. Sixty-eight percent had participated in multi professional training in non-technical skills, while 54% had passed the advanced trauma life support(ATLS) course. Fifty-one percent were trained in damage control surgery. A median of one course per team leader was needed to comply with the new proposed national standards. Team leaders considered training in damage control surgery the most needed educational objective. CONCLUSIONS: Level of experience among team leaders was highly variable and their educational background insufficient according to international and proposed national standards. Proposed national standards should be urgently implemented to ensure equal access to high quality trauma care. PMID- 21975089 TI - Impact of antiretroviral therapy on fertility desires among HIV-infected persons in rural Uganda. AB - BACKGROUND: Little is known about the fertility desires of HIV infected individuals on highly active antiretroviral therapy (HAART). In order to contribute more knowledge to this topic we conducted a study to determine if HIV infected persons on HAART have different fertility desires compared to persons not on HAART, and if the knowledge about HIV transmission from mother-to-child is different in the two groups. METHODS: The study was a cross-sectional survey comparing two groups of HIV-positive participants: those who were on HAART and those who were not. Semi-structured interviews were conducted with 199 HIV patients living in a rural area of western Uganda. The desire for future children was measured by the question in the questionnaire "Do you want more children in future." The respondents' HAART status was derived from the interviews and verified using health records. Descriptive, bivariate and multivariate methods were used to analyze the relationship between HAART treatment status and the desire for future children. RESULTS: Results from the multivariate logistic regression model indicated an adjusted odds ratio (OR) of 1.08 (95% CI 0.40-2.90) for those on HAART wanting more children (crude OR 1.86, 95% CI 0.82-4.21). Statistically significant predictors for desiring more children were younger age, having a higher number of living children and male sex. Knowledge of the risks for mother-to-child-transmission of HIV was similar in both groups. CONCLUSIONS: The conclusions from this study are that the HAART treatment status of HIV patients did not influence the desire for children. The non-significant association between the desire for more children and the HAART treatment status could be caused by a lack of knowledge in HIV-infected persons/couples about the positive impact of HAART in reducing HIV transmission from mother-to-child. We recommend that the health care system ensures proper training of staff and appropriate communication to those living with HIV as well as to the general community. PMID- 21975091 TI - Experimental evolution reveals antagonistic pleiotropy in reproductive timing but not life span in Caenorhabditis elegans. AB - Many mutations that dramatically extend life span in model organisms come with substantial fitness costs. Although these genetic manipulations provide valuable insight into molecular modulators of life span, it is currently unclear whether life-span extension is unavoidably linked to fitness costs. To examine this relationship, we evolved a genetically heterogeneous population of Caenorhabditis elegans for 47 generations, selecting for early fecundity. We asked whether an increase in early fecundity would necessitate a decrease in longevity or late fecundity (antagonistic pleiotropy). Caenorhabditis elegans experimentally evolved for increased early reproduction and decreased late reproduction but suffered no total fitness or life-span costs. Given that antagonistic pleiotropy among these traits has been previously demonstrated in some cases, we conclude that the genetic constraint is not absolute, that is, it is possible to uncouple longevity from early fecundity using genetic variation segregating within and among natural populations. PMID- 21975092 TI - Gait speed, body composition, and dementia. The EPIDOS-Toulouse cohort. AB - BACKGROUND: Slow gait speed (GS) predicts dementia, but this association might be mediated by body composition parameters like total fat mass (TFM) or total lean mass (TLM). The aim of the study was to evaluate whether GS, TLM, and TFM were associated factors with an increased risk for subsequent dementia in community dwelling older women. METHODS: A case-control study was nested in the EPIDemiologie de l'OSteoporose cohort. GS (at usual pace more than 6 m), TLM, and TFM (assessed by dual energy x-ray absorptiometry) were measured at baseline. Cognitive performance was evaluated at baseline and at 7 years of follow-up. The presence of dementia was assured by two blinded memory experts based on best practice and validated criteria. Multivariate logistic regression models assessed the association of GS, TLM, and TFM with dementia risk. RESULTS: Of the initial 1,462 women, 75 years old and older, 647 (43.4%) were cognitively intact at baseline and had a full cognitive assessment at 7 years (145 of them developed dementia). Controlled for covariates (demographics, physical activity, self reported disabilities, and comorbidities), GS was an independent associated factor for subsequent dementia as a continuous variable (odds ratio [OR] 2.28, 95% CI: 1.32-3.94) and as a categorized variable (OR 2.38, 95% CI: 1.28-4.43 highest vs lowest quartile). Neither interaction with GS nor a statistically significant association with dementia risk was found for TLM and TFM. CONCLUSIONS: GS was an independent associated factor for subsequent dementia not mediated by TLM or TFM. PMID- 21975093 TI - Effect of partial wrist denervation on wrist kinesthesia: wrist denervation does not impair proprioception. AB - PURPOSE: To evaluate the potential effect of partial wrist denervation on wrist kinesthesia, we hypothesized that anesthetizing the anterior interosseous nerve and the posterior interosseous nerve does not impair the kinesthesia. METHODS: We performed a double-blinded, prospective, randomized study on 80 healthy volunteers (20-54 y old) to compare the ability to detect active and passive wrist movement in 2 conditions. The test group received an anesthetic block of the anterior and posterior interosseous nerves, and the control group subjects received an injection of saline. The kinesthesia of the 2 groups was then tested in 2 conditions by measuring the error in an active and passive wrist repositioning task. Results were analyzed using a repeated measures analysis of variance. RESULTS: In both active and passive conditions, there was no difference in the repositioning errors between the test group and the control group. CONCLUSIONS: Our results show that kinesthesia is not impaired by blocking the anterior and posterior interosseous nerves. These findings are consistent for both active and passive motion. The study gives strong evidence that partial denervation does not impair wrist kinesthesia. However, because only kinesthesia was studied, we cannot conclude that partial denervation is a totally safe procedure for all aspects of proprioception. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I. PMID- 21975090 TI - Muscle strength and BMI as predictors of major mobility disability in the Lifestyle Interventions and Independence for Elders pilot (LIFE-P). AB - BACKGROUND: Muscle weakness and obesity are two significant threats to mobility facing the increasing number of older adults. To date, there are no studies that have examined the association of strength and body mass index (BMI) on event rates on a widely used performance measure of major mobility disability. METHODS: This study was a secondary analysis of a randomized controlled trial in which sedentary functionally limited participants (70-89 years, Short Physical Performance Battery <= 9) who were able to complete a 400-m walk test at baseline were randomized to a physical activity or health education intervention and reassessed for major mobility disability every 6 months for up to 18 months. We evaluated whether baseline grip strength and BMI predicted failure to complete the 400-m walk test in 15 minutes or less (major mobility disability). RESULTS: Among N = 406 participants with baseline measures, lower grip strength was associated with an increased risk for developing major mobility disability, with and without covariate adjustment (p < .01): The hazard ratio (95% confidence interval) for the lowest versus high sex-specific quartile of grip strength was 6.11 (2.24-16.66). We observed a U-shaped relationship between baseline BMI and the risk of developing major mobility disability, such that the risk for participants with a BMI of 25-29 kg/m(2) was approximately half that of participants with BMI less than 25 or 30 kg/m(2) or more (p = .04 in fully adjusted analyses). CONCLUSIONS: Our data highlight the importance of muscle weakness, low BMI, and obesity as risk factors for major mobility disability in older adults. Being overweight may be protective for major mobility disability. PMID- 21975094 TI - A ganglion within the ulnar nerve and communication with the distal radioulnar joint via an articular branch: case report. AB - An intraneural ganglion is rare, and involvement of an articular nerve may suggest a possible pathogenesis. We report an intraneural ganglion of the ulnar nerve with a connection to the distal radioulnar joint via the articular branch. We excised the ganglion, the stalk, and the articular branch. To date, there has been no recurrence. PMID- 21975095 TI - Assessing the impact of antibiotic prophylaxis in outpatient elective hand surgery: a single-center, retrospective review of 8,850 cases. AB - PURPOSE: Prophylactic antibiotics have been shown to prevent surgical site infection (SSI) after some gastrointestinal, orthopedic, and plastic surgical procedures, but their efficacy in clean, elective hand surgery is unclear. Our aims were to assess the efficacy of preoperative antibiotics in preventing SSI after clean, elective hand surgery, and to identify potential risk factors for SSI. METHODS: We queried the database from an outpatient surgical center by Current Procedural Terminology code to identify patients who underwent elective hand surgery. For each medical record, we collected patient demographics and characteristics along with preoperative, intraoperative, and postoperative management details. The primary outcome of this study was SSI, and secondary outcomes were wound dehiscence and suture granuloma. RESULTS: From October 2000 through October 2008, 8,850 patient records met our inclusion criteria. The overall SSI rate was 0.35%, with an average patient follow-up duration of 79 days. The SSI rates did not significantly differ between patients receiving antibiotics (0.54%; 2,755 patients) and those who did not (0.26%; 6,095 patients). Surgical site infection was associated with smoking status, diabetes mellitus, and longer procedure length irrespective of antibiotic use. Subgroup analysis revealed that prophylactic antibiotics did not prevent SSI in male patients, smokers, or diabetics, or for procedure length less than 30 minutes, 30 to 60 minutes, and greater than 60 minutes. CONCLUSIONS: Prophylactic antibiotic administration does not reduce the incidence of SSI after clean, elective hand surgery in an outpatient population. Moreover, subgroup analysis revealed that prophylactic antibiotics did not reduce the frequency of SSI among patients who were found to be at higher risk in this study. We identified 3 factors associated with the development of SSI in our study: diabetes mellitus status, procedure length, and smoking status. Given the potential harmful complications associated with antibiotic use and the lack of evidence that prophylactic antibiotics prevent SSIs, we conclude that antibiotics should not be routinely administered to patients who undergo clean, elective hand surgery. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III. PMID- 21975096 TI - Arthroscopic treatment of an osteochondral lesion in a child with chronic wrist pain: case report. AB - Osteochondral lesions of the wrist are rare in the pediatric and adolescent population. We report a case of an osteochondral lesion of the lunate facet of the radiocarpal joint in a 6-year-old girl with chronic wrist pain after falling on her hand. Arthroscopic debridement of the osteochondral fragment relieved the symptoms and improved wrist function. Osteochondral lesions should be considered in the differential diagnosis of chronic wrist pain in children with a history of trauma. PMID- 21975097 TI - Oblique ulnar styloid osteotomy--a treatment for ulnar styloid impaction syndrome. AB - PURPOSE: We report a series of 5 patients (mean age, 41 y) presenting with ulnar styloid impingement syndrome (USIS) and treated by an oblique ulnar styloid osteotomy. The purpose of the study was to determine whether the osteotomy is an effective method for treating USIS. METHODS: The diagnosis of USIS was made based on a history of ulnar-sided wrist pain supported by clinical and radiological findings. Clinical assessment included provocative tests to differentiate USIS from pain associated with ulnocarpal impaction syndrome. The ulnar styloid length was assessed with a posteroanterior X-ray using the methods of Garcia-Elias and Biyani. The ulnar styloid was deemed excessively long if the ulnar styloid process index was greater than 0.21 or if the overall styloid length was greater than 6 mm. Ulnar variance was recorded. All wrists were assessed by computed tomography arthrography and magnetic resonance imaging studies to rule out any associated soft tissue abnormalities, including ligamentous injuries. Preoperative and postoperative pain levels were recorded using a pain scoring system. RESULTS: Patients were followed up for a mean of 46 months. Before surgery, the mean styloid length was 10 mm, and the ulnar styloid process index was 0.32. The reported pain score was significantly reduced following surgery and all patients, except one, returned to premorbid levels of activity. CONCLUSIONS: Oblique ulnar styloid osteotomy is an effective means of relieving impaction of the ulnar styloid while preserving the integrity of the intrinsic ulnar styloid ligaments. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 21975098 TI - Epidemiology of upper extremity replantation surgery in the United States. AB - PURPOSE: Replantation remains an important technique in the management of hand trauma. Given the resources necessary for a successful replantation program, regionalization of replantation care may ultimately be required. The purposes of this study were to analyze the geographic distribution of upper extremity replant procedures, analyze factors of patients undergoing replantation, and characterize the facilities performing these procedures. METHODS: We performed a cohort study using the National Inpatient Sample of the Healthcare Cost and Utilization Project from 2001, 2004, and 2007. Patients with an upper extremity amputation were defined, and a subgroup of patients undergoing replantation was delineated. We analyzed patient demographics and injury characteristics and characteristics of treating facilities. RESULTS: A total of 9,407 patients were treated for upper extremity amputation, 1,361 of whom underwent replantation. Mean age of patients undergoing replantation was 36 years (range, 0-86 y), compared with 44 years (range, 0-104 y) in patients not undergoing replantation. Hospital charges (P < .001) and length of stay (P < .001) were significantly higher for patients with replantations versus those without replantations. Patients treated at teaching facilities were more likely to undergo replantation than those at a non-teaching facility (19% replantation rate at teaching hospitals vs 7% at non-teaching). Large hospitals and urban hospitals were more likely to perform replantation. Self-pay, Medicare, and Medicaid patients all had lower replantation rates than patients with other payer status. CONCLUSIONS: Patients who undergo replantation are younger, incur higher hospital charges, and have longer hospital stays compared with patients who do not undergo replantation. Treatment at large, urban, and teaching facilities is associated with higher replantation rates. Payer status appears to have some bearing on replantation rates. Further studies are needed to better elucidate the relationship between patient and injury characteristics, treatment location, and outcomes, to adequately distribute the finite resources for replantation. TYPE OF STUDY/LEVEL OF EVIDENCE: Economic and Decision Analysis IV. PMID- 21975099 TI - Orf infection of the hand. PMID- 21975101 TI - Ancient schwannoma of the hand. AB - Ancient schwannoma is a schwannoma subtype, characterized by extensive degeneration and diffuse hypocellular areas. These changes are believed to occur because it takes a long time for ancient schwannomas to develop. Schwannomas with these degenerative changes can be misdiagnosed as sarcomas or other soft-tissue neoplasms. We present a case of a slowly enlarging ancient schwannoma of the thenar area in a 67-year-old woman. The differential diagnosis included atypical soft tissue sarcomas and tumors of neural origin. The combination of ultrasound and magnetic resonance imaging findings provided features that narrowed the differential diagnosis, and histology confirmed the presence of an encapsulated schwannoma with extensive myxomatous degeneration and multiple vessel thrombosis. The clinical, radiological, and histological features and the diagnostic approach of this rare entity are described. PMID- 21975100 TI - Performance of simplified scoring systems for hand diagrams in carpal tunnel syndrome screening. AB - PURPOSE: Katz et al have published a standardized scoring system of hand diagrams for carpal tunnel syndrome. The purpose of this study was to quantitatively evaluate an alternative scoring of the hand diagram for detection of carpal tunnel syndrome. METHODS: In a prospective study of 1,107 workers, 221 workers with hand symptoms completed hand diagrams and electrodiagnostic testing for carpal tunnel syndrome. Scoring algorithms for the hand diagrams included the Katz rating; a median nerve digit score (0-2) with a maximum of 2 symptomatic digits of thumb, index, and long fingers; and isolated digit scores (0-1) of thumb, index, or long finger. Intraclass correlation coefficients quantified inter-rater reliability. Sensitivity, specificity, and logistic regression analyses evaluated the scoring systems' ability to predict abnormal median nerve conduction. RESULTS: One hundred ten subjects illustrated symptoms within the median nerve distribution. All scoring systems demonstrated substantial inter rater reliability. "Classic" or "probable" Katz scores, median nerve digit score of 2, and positive long finger scores were significantly associated with abnormal median nerve distal sensory latency and median-ulnar difference. Abnormal distal motor latency was significantly associated with the median nerve digit score of 2 and positive long finger scores. Increasing Katz scores from "possible" to "probable" and "classic" were not associated with greater odds of electrodiagnostic abnormality. Positive long finger scores performed at least as well as the most rigorous scoring by Katz. CONCLUSIONS: Symptoms diagrammed within the median nerve distribution are associated with abnormal nerve conduction among workers. The median nerve digit score and the long finger score offer increased ease of use compared to the Katz method, while maintaining similar performance characteristics. The long finger appears best suited for isolated digit scoring to predict abnormal median nerve conduction in a working population. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II. PMID- 21975102 TI - [Syphilitic arthropathy: a case report with positive PCR]. PMID- 21975106 TI - Trace elements of normal, benign hypertrophic and cancerous tissues of the human prostate gland investigated by neutron activation analysis. AB - The Ag, Co, Cr, Fe, Hg, Rb, Sb, Sc, Se, and Zn contents in normal (n=37), benign hypertrophic (n=43), and cancerous tissues (n=60) of the human prostate gland were investigated by neutron activation analysis. Mean values (M+/-SEpsilonMU) for content (mg/kg, dry weight basis) of trace elements in the normal tissue were: Ag-0.048+/-0.009, Co-0.045+/-0.004, Cr-0.53+/-0.08, Fe-111+/-9, Hg-0.056+/ 0.011, Rb-12.7+/-0.9, Sb-0.045+/-0.007, Sc-0.029+/-0.005, Se-0.70+/-0.04, and Zn 1000+/-110, respectively. It was observed that in benign hypertrophic tissues the contents of Co, Cr, Hg, Sb, and Se were higher than in normal tissues, with statistically significant differences. The contents of Co, Rb, Sc, and Zn were significantly lower and those of Ag, Cr, Fe, Hg, and Sb were significantly higher in cancerous tissues than in normal tissues. PMID- 21975107 TI - Automated synthesis of [18F]gefitinib on a modular system. AB - In recent years, [(18)F]gefitinib PET has successfully been employed for a number of applications ranging from oncology to in vivo studies of drug transporter proteins. We here report a reliable, automated procedure for routine synthesis of this radiotracer on an Eckert and Ziegler modular system. The 3-step radiosynthesis followed by preparative HPLC-purification provided [(18)F]gefitinib in 17.2+/-3.3% (n=22) overall decay-corrected radiochemical yield with radiochemical purity >99% in a total synthesis time of about 2.5h. PMID- 21975108 TI - A review of electrodeposition methods for the preparation of alpha-radiation sources. AB - This paper addresses an approach to the theory and practice of electrodeposition processes of alpha-emitting nuclides. Some of the main contributions made to this field are reviewed, including the rotating disk electrode technique. Also, several interpretations concerning the electrodeposition process as well as a number of practical recommendations are included in the study. PMID- 21975109 TI - Vector autoregression, structural equation modeling, and their synthesis in neuroimaging data analysis. AB - Vector autoregression (VAR) and structural equation modeling (SEM) are two popular brain-network modeling tools. VAR, which is a data-driven approach, assumes that connected regions exert time-lagged influences on one another. In contrast, the hypothesis-driven SEM is used to validate an existing connectivity model where connected regions have contemporaneous interactions among them. We present the two models in detail and discuss their applicability to FMRI data, and their interpretational limits. We also propose a unified approach that models both lagged and contemporaneous effects. The unifying model, structural vector autoregression (SVAR), may improve statistical and explanatory power, and avoid some prevalent pitfalls that can occur when VAR and SEM are utilized separately. PMID- 21975110 TI - Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia: a randomized clinical trial - the SMART trial protocol. AB - BACKGROUND: Treatment of schizophrenia frequently includes prolonged benzodiazepine administration despite a lack of evidence of its use. It is often difficult to discontinue benzodiazepines because of the development of dependence. We aim to assess if melatonin can facilitate the withdrawal of prolonged benzodiazepine administration in patients with schizophrenia. Furthermore, we aim to investigate the association of benzodiazepine dose reduction with the following clinically important variables: sleep, psychophysiology, cognition, social function, and quality of life. METHODS/DESIGN: Randomized, blinded, two-armed, parallel superiority trial. We plan to include 80 consenting outpatients diagnosed with schizophrenia or schizoaffective disorder, 18-55 years of age, treated with antipsychotic drug(s) and at least one benzodiazepine derivative for the last three months before inclusion. EXCLUSION CRITERIA: currently under treatment for alcohol or drug abuse, aggressive or violent behavior, known mental retardation, pervasive developmental disorder, dementia, epilepsy, terminal illness, severe co morbidity, inability to understand Danish, allergy to melatonin, lactose, starch, gelatin, or talc, hepatic impairment, pregnancy or nursing, or lack of informed consent. After being randomized to prolonged-release melatonin (Circadin(r)) 2 mg daily or matching placebo, participants are required to slowly taper off their benzodiazepine dose. The primary outcome measure is benzodiazepine dose at 6 months follow-up. Secondary outcome measures include sleep, psychophysiological, and neurocognitive measures. Data are collected at baseline and at 6 months follow-up regarding medical treatment, cognition, psychophysiology, sleep, laboratory tests, adverse events, psychopathology, social function, and quality of life. Data on medical treatment, cognition, psychophysiology, adverse events, social function, and quality of life are also collected at 2 and 4 months follow up. DISCUSSION: The results from this trial will examine whether melatonin has a role in withdrawing long-term benzodiazepine administration in schizophrenia patients. This group of patients is difficult to treat and therefore often subject to polypharmacy which may play a role in the reduced life expectancy of patients compared to the background population. The results will also provide new information on the association of chronic benzodiazepine treatment with sleep, psychophysiology, cognition, social function, and quality of life. Knowledge of these important clinical aspects is lacking in this group of patients. TRIAL REGISTRATION: ClinicalTrials NCT01431092. PMID- 21975111 TI - Identification and localization of the structural proteins of anguillid herpesvirus 1. AB - Many of the known fish herpesviruses have important aquaculture species as their natural host, and may cause serious disease and mortality. Anguillid herpesvirus 1 (AngHV-1) causes a hemorrhagic disease in European eel, Anguilla anguilla. Despite their importance, fundamental molecular knowledge on fish herpesviruses is still limited. In this study we describe the identification and localization of the structural proteins of AngHV-1. Purified virions were fractionated into a capsid-tegument and an envelope fraction, and premature capsids were isolated from infected cells. Proteins were extracted by different methods and identified by mass spectrometry. A total of 40 structural proteins were identified, of which 7 could be assigned to the capsid, 11 to the envelope, and 22 to the tegument. The identification and localization of these proteins allowed functional predictions. Our findings include the identification of the putative capsid triplex protein 1, the predominant tegument protein, and the major antigenic envelope proteins. Eighteen of the 40 AngHV-1 structural proteins had sequence homologues in related Cyprinid herpesvirus 3 (CyHV-3). Conservation of fish herpesvirus structural genes seemed to be high for the capsid proteins, limited for the tegument proteins, and low for the envelope proteins. The identification and localization of the structural proteins of AngHV-1 in this study adds to the fundamental knowledge of members of the Alloherpesviridae family, especially of the Cyprinivirus genus. PMID- 21975113 TI - Unraveling the brainstem mysteries in late-preterm infants. PMID- 21975114 TI - Anatomy in the Third Reich. PMID- 21975115 TI - New insights in prism orientation within human enamel. AB - The knowledge about the orientation of the prisms in human dental enamel is mainly based on morphological observations (light optical, SEM, etc.). Hence there are many schematic drawings, showing the orientation as seen in the microscope. Locally resolved direct measurements of the orientations, proofing the observations, have not been done in detail up to now. X-ray diffraction methods adapted from material science are used in this study, providing directly the orientation of the crystallites in the examined positions. Hereby new and better detailed information was obtained, showing the orientation of the prisms and giving information about their intrinsic structure. Based on the measurements, existing prism orientation models can be enhanced and two structural suggestions can be made, showing possible inner building principles for the prisms. Future planned measurements will even allow deciding which of the two models is more likely. PMID- 21975116 TI - The expression of antioxidant enzymes in the gingivae of type 2 diabetics with chronic periodontitis. AB - OBJECTIVES: There is controversial evidence regarding the levels of antioxidant molecules in type 2 diabetes periodontitis patients. Thus, the aim of the present study was to evaluate the gene expression of antioxidant enzymes in the gingival tissue of poorly and well-controlled type 2 diabetic subjects with chronic periodontitis (CP). DESIGN: Gingival biopsies were harvested from systemically and periodontally healthy subjects (n=12), systemically healthy subjects with CP (n=15), well-controlled (n=8) and poorly controlled (n=14) diabetic subjects with CP. The messenger RNA (mRNA) levels of peroxiredoxin (PRDX) 1 and 2, catalase (CAT), glutathione peroxidase (GPX1) and superoxide dismutase (SOD) 1 and 2 were measured by quantitative polymerase chain reaction (qPCR). RESULTS: The results showed that PRDX1 and GPX1 were up-regulated by periodontitis (p<0.05), independently of the glycaemic status, whilst PRDX2 and SOD2 genes were slightly influenced by periodontitis, but significantly induced when periodontitis was associated with DM, especially under a poor glycaemic control (p<0.05). Moreover, CAT and SOD1 expressions were not significantly influenced by any of these inflammatory disorders (p>0.05). CONCLUSION: In conclusion, both PRDX1 and GPX1 were overexpressed in CP whilst PRDX2 and SOD2 were up-regulated especially in the poorly controlled diabetic group with CP. PMID- 21975117 TI - Association between mouth opening and upper body movement with intake of different-size food pieces during eating. AB - Head rotation is coordinated with mandibular movement during mouth opening, and the range of head rotation and mouth opening change with food size. However, past research did not include upper body movement, and no reports have related head and mandibular movement during realistic eating. The purpose of this study was to analyse head and mandibular movements with intake of different-sized food pieces during realistic eating. The test food consisted of apple cut into two different cube sizes (10mm and 20mm). Head and mandibular movements of 20 healthy young adults eating the apple pieces were simultaneously recorded in three dimensions by a wireless opto-electronic system. Reflective markers were attached to the upper lip and chin to measure the mouth opening range. Five markers were attached to eyeglasses frames to measure linear motion and rotation of the head. One marker was attached to the jugular notch of the sternum to measure linear motion of the upper body. Linear motion, and the inclination angle of the head and upper body, and mouth opening range were compared during intake of different-sized apple pieces. Mouth opening, head-neck rotation angle and the amount of upper body forward translation and inclination increased with larger apple pieces. However, isolated relative head motion was stabilized. We conclude that upper body forward motion and head-neck rotation assist mouth opening whilst stabilizing head orientation, and that the range of head-neck rotation angle, upper body translation and range of mouth opening change with food size during realistic eating. PMID- 21975118 TI - Orthodontic anomalies and malocclusions in Late Antique and Early Mediaeval period in Croatia. AB - OBJECTIVE: Malocclusions are relative infrequently analysed in bioarchaeological investigations and if investigated the samples are very small. This research provides analysis of orthodontic anomalies of even 1118 individuals from the Late Antique (LA) and Early Mediaeval (EM) period. Aims were to describe the prevalence of orthodontic anomalies in this historical period and to analyse which orthodontic anomalies are best suitable for bioarchaeological investigations. METHODS: 1118 skulls were examined for anomalies of tooth number, tooth displacement (rotation, malposition, diastema and crowding) as well as for malocclusions. RESULTS: The prevalence of hypodontia in the LA was 41.02% and 30.61% in the EM sample. Tooth displacement was noticed in 15.63% individuals from the LA and in 12.42% individuals from EM. About 26% of the LA sample and 7.19% of the EM sample were affected with tooth crowding and the difference was statistically significant. CONCLUSION: Orthodontic anomalies affecting only one tooth or group of teeth are more suitable for examination in bioarchaeological investigations than orthodontic features requiring presence of both jaws and all or almost all teeth. Clinical investigation protocols and methodology should be adopted for bioarchaeological researches and international standards and recommendations should be established for this kind of investigation on skeletal remains. PMID- 21975119 TI - Pre-steady state kinetic studies show that an abasic site is a cognate lesion for the yeast Rev1 protein. AB - Rev1 is a eukaryotic DNA polymerase that rescues replication forks stalled at sites of DNA damage by inserting nucleotides opposite the damaged template bases. Yeast genetic studies suggest that Rev1 plays an important role in rescuing replication forks stalled at one of the most common forms of DNA damage, an abasic site; however, steady state kinetic studies suggest that an abasic site acts as a significant block to nucleotide incorporation by Rev1. Here we examined the pre-steady state kinetics of nucleotide incorporation by yeast Rev1 with damaged and non-damaged DNA substrates. We found that yeast Rev1 is capable of rapid nucleotide incorporation, but only a small fraction of the protein molecules possessed this robust activity. We characterized the nucleotide incorporation by the catalytically robust fraction of yeast Rev1 and found that it efficiently incorporated dCTP opposite a template abasic site under pre-steady state conditions. We conclude from these studies that the abasic site is a cognate lesion for Rev1. PMID- 21975120 TI - Human MutS and FANCM complexes function as redundant DNA damage sensors in the Fanconi Anemia pathway. AB - The Fanconi Anemia (FA) pathway encodes a DNA damage response activated by DNA damage-stalled replication forks. Current evidence suggests that the FA pathway initiates with DNA damage recognition by the FANCM complex (FANCM/FAAP24/MHF). However, genetic inactivation of FANCM in mouse and DT40 cells causes only a partial defect in the FA pathway activation, suggesting the existence of redundant DNA damage sensors. Here we show that the MutS homologs function in this capacity. A RNAi screen revealed that MSH2 silencing caused defective FA pathway activation, as assessed by damage-induced FANCD2 mono-ubiquitination. A similar FA pathway defect was observed with MSH3 or MSH6 silencing. MSH2 depletion caused cellular phenotypes associated with defective FA pathway, including mitomycin C hypersensitivity and chromosomal instability. Further, silencing of FANCM in MSH2 deficient HEC59 cells caused a more severe FA defect relative to comparable silencing in MSH2 complemented HEC59+Chr2 cells, suggesting redundant functions between MSH2 and FANCM. Consistent with this hypothesis, depletion of MSH2 resulted in defective chromatin localization of the FA core complex upon DNA damage. Further, MSH2 was co-purified and co immunoprecipitated with FA core complex components. Taken together, our results suggest that human MutS homologs and FANCM complexes function as redundant DNA damage sensors of the FA pathway. PMID- 21975121 TI - Electrochemical biosensors employing an internal electrode attachment site and achieving reversible, high gain detection of specific nucleic acid sequences. AB - Electrochemical DNA (E-DNA) sensors, which are rapid, reagentless, and readily integrated into microelectronics and microfluidics, appear to be a promising alternative to optical methods for the detection of specific nucleic acid sequences. Keeping with this, a large number of distinct E-DNA architectures have been reported to date. Most, however, suffer from one or more drawbacks, including low signal gain (the relative signal change in the presence of complementary target), signal-off behavior (target binding reduces the signaling current, leading to poor gain and raising the possibility that sensor fouling or degradation can lead to false positives), or instability (degradation of the sensor during regeneration or storage). To remedy these problems, we report here the development of a signal-on E-DNA architecture that achieves both high signal gain and good stability. This new sensor employs a commercially synthesized, asymmetric hairpin DNA as its recognition and signaling probe, the shorter arm of which is labeled with a redox reporting methylene blue at its free end. Unlike all prior E-DNA architectures, in which the recognition probe is attached via a terminal functional group to its underlying electrode, the probe employed here is affixed using a thiol group located internally, in the turn region of the hairpin. Hybridization of a target DNA to the longer arm of the hairpin displaces the shorter arm, allowing the reporter to approach the electrode surface and transfer electrons. The resulting device achieves signal increases of ~800% at saturating target, a detection limit of just 50 pM, and ready discrimination between perfectly matched sequences and those with single nucleotide polymorphisms. Moreover, because the hairpin probe is a single, fully covalent strand of DNA, it is robust to the high stringency washes necessary to remove the target, and thus, these devices are fully reusable. PMID- 21975122 TI - Transcriptional response of peripheral blood mononuclear cells to recombinant human growth hormone in a routine four-days IGF-I generation test. AB - BACKGROUND: There are very few laboratory markers which reflect the biological sensitivity of children to recombinant human growth hormone (rhGH) treatment. Genome-wide transcriptional changes in peripheral blood mononuclear cells (PBMC) have been widely used as functional readout for different pharmacological stimuli. OBJECTIVE: To characterize transcriptional changes in PBMC induced by rhGH during a routine short-term IGF-I generation test (IGFGT) in children with growth disorders. MATERIALS AND METHODS: Blood was obtained for IGF-I determination and RNA-preparation from PBMC of 12 children before and after 4days treatment with 30MUgrhGH/kg body weight/day s.c. Transcriptional changes were assessed by cDNA-microarrays in the first six children. Selected genes were validated in all 12 cases by RT-qPCR. RESULTS: Serum IGF-I rose in all patients except one (p<0.0001), confirming biological response to rhGH. Unsupervised microarray data analysis in the first six children revealed 313 transcripts with abundant transcriptional changes but considerable inter-individual variability of response patterns. Many patients showed a large cluster of up-regulated genes, including EGR1, EGR2, FOS and to a lesser extent STAT2 and 5b. Exemplarily, EGR1, EGR2 and FOS data were independently reproduced by RT-qPCR. Gene ontology analysis revealed that pathways involved in cell proliferation and immune functions were significantly over represented. CONCLUSION: The IGFGT is a suitable method for measuring reproducible and biologically conclusive transcriptional changes in PBMC. As our unsupervised data analysis strategy exposed a considerable inter-individual variability of response profiles a search for molecules of diagnostic and even prognostic value needs to be based on large long-term studies. PMID- 21975123 TI - Prevalence of at-risk genotypes for genotoxic effects decreases with age in a randomly selected population in Flanders: a cross sectional study. AB - BACKGROUND: We hypothesized that in Flanders (Belgium), the prevalence of at-risk genotypes for genotoxic effects decreases with age due to morbidity and mortality resulting from chronic diseases. Rather than polymorphisms in single genes, the interaction of multiple genetic polymorphisms in low penetrance genes involved in genotoxic effects might be of relevance. METHODS: Genotyping was performed on 399 randomly selected adults (aged 50-65) and on 442 randomly selected adolescents. Based on their involvement in processes relevant to genotoxicity, 28 low penetrance polymorphisms affecting the phenotype in 19 genes were selected (xenobiotic metabolism, oxidative stress defense and DNA repair, respectively 13, 6 and 9 polymorphisms). Polymorphisms which, based on available literature, could not clearly be categorized a priori as leading to an 'increased risk' or a 'protective effect' were excluded. RESULTS: The mean number of risk alleles for all investigated polymorphisms was found to be lower in the 'elderly' (17.0 +/- 2.9) than the 'adolescent' (17.6 +/- 3.1) subpopulation (P = 0.002). These results were not affected by gender nor smoking. The prevalence of a high (> 17 = median) number of risk alleles was less frequent in the 'elderly' (40.6%) than the 'adolescent' (51.4%) subpopulation (P = 0.002). In particular for phase II enzymes, the mean number of risk alleles was lower in the 'elderly' (4.3 +/- 1.6 ) than the 'adolescent' age group (4.8 +/- 1.9) P < 0.001 and the prevalence of a high (> 4 = median) number of risk alleles was less frequent in the 'elderly' (41.3%) than the adolescent subpopulation (56.3%, P < 0.001). The prevalence of a high (> 8 = median) number of risk alleles for DNA repair enzyme-coding genes was lower in the 'elderly' (37,3%) than the 'adolescent' subpopulation (45.6%, P = 0.017). CONCLUSIONS: These observations are consistent with the hypothesis that, in Flanders, the prevalence of at-risk alleles in genes involved in genotoxic effects decreases with age, suggesting that persons carrying a higher number of at risk alleles (especially in phase II xenobiotic-metabolizing or DNA repair genes) are at a higher risk of morbidity and mortality from chronic diseases. Our findings also suggest that, regarding risk of disease associated with low penetrance polymorphisms, multiple polymorphisms should be taken into account, rather than single ones. PMID- 21975124 TI - Comparison of endpoint data treatment methods for estimation of kinematics and kinetics near impact during the tennis serve. AB - Tennis stroke mechanics have attracted considerable biomechanical analysis, yet current filtering practice may lead to erroneous reporting of data near the impact of racket and ball. This research had three aims: (1) to identify the best method of estimating the displacement and velocity of the racket at impact during the tennis serve, (2) to demonstrate the effect of different methods on upper limb kinematics and kinetics and (3) to report the effect of increased noise on the most appropriate treatment method. The tennis serves of one tennis player, fit with upper limb and racket retro-reflective markers, were captured with a Vicon motion analysis system recording at 500 Hz. The raw racket tip marker displacement and velocity were used as criterion data to compare three different endpoint treatments and two different filters. The 2nd-order polynomial proved to be the least erroneous extrapolation technique and the quintic spline filter was the most appropriate filter. The previously performed "smoothing through impact" method, using a quintic spline filter, underestimated the racket velocity (9.1%) at the time of impact. The polynomial extrapolation method remained effective when noise was added to the marker trajectories. PMID- 21975126 TI - Quantifying the health impacts of future changes in temperature in California. AB - BACKGROUND: Several epidemiological studies demonstrate associations between high summer temperatures and increased mortality. However, the quantitative implications of projected future increases in temperature have not been well characterized. OBJECTIVE: This study quantifies the effects of projected future temperatures on both mortality and morbidity in California, including the potential effects of mitigation. DATA AND METHODS: We first estimated the association between temperature and mortality for populations close to weather stations throughout the state. These dose-response estimates for mortality were then combined with local measures of current and projected changes in population, and projected changes in temperature, using a baseline of average temperatures from 1961 to 1990, for the years 2025 and 2050. The latter were based on two greenhouse gas emissions scenarios (A2 and B1) developed for the Intergovernmental Panel on Climate Change. In addition, we assessed the impacts of future adaptation through use of air conditioners. Several sensitivity analyses were conducted to determine the likely range of estimates. RESULTS: These analyses indicate that for the high emissions scenario, the central estimate of annual premature mortality ranges from 2100 to 4300 for the year 2025 and from 6700 to 11,300 for 2050. The highest estimates are from the models that use age-specific dose-response functions, while the low estimates are from the models that adjust for ozone. Estimates using the low emissions scenario are roughly half of these estimates. Mitigation based on our estimates of the effects of 10% and 20% increase in air conditioner use would generate reductions of 16% and 33% in the years 2025 and 2050, respectively. CONCLUSION: Our estimates suggest significant public health impacts associated with future projected increases in temperature. PMID- 21975125 TI - Epstein - Barr virus Latent Membrane Protein 1 suppresses reporter activity through modulation of promyelocytic leukemia protein-nuclear bodies. AB - The Epstein-Barr virus (EBV) encoded Latent Membrane Protein 1 (LMP1) has been shown to increase the expression of promyelocytic leukemia protein (PML) and the immunofluorescent intensity of promyelocytic leukemia nuclear bodies (PML NBs). PML NBs have been implicated in the modulation of transcription and the association of reporter plasmids with PML NBs has been implicated in repression of reporter activity. Additionally, repression of various reporters in the presence of LMP1 has been noted. This study demonstrates that LMP1 suppresses expression of reporter activity in a dose responsive manner and corresponds with the LMP1 induced increase in PML NB intensity. Disruption of PML NBs with arsenic trioxide or a PML siRNA restores reporter activity. These data offer an explanation for previously conflicting data on LMP1 signaling and calls attention to the possibility of false-positives and false-negatives when using reporter assays as a research tool in cells expressing LMP1. PMID- 21975127 TI - Multiple organ inflammatory response to portosystemic shunt in the rat. AB - Portosystemic shunt surgery is the best procedure to prevent recurrent bleeding of esophageal varices, but carries a high risk of postoperative inflammatory complications, including hepatic encephalopathy. Thus, portosystemic shunting procedures could induce a systemic inflammatory response with multiple organ dysfunction syndrome, including hepatic encephalopathy. To verify this hypothesis we used male Wistar rats at 6 weeks of postoperative evolution: Control (CR; n=14), Sham-operated (SO; n=8) and rats with end-to-side portacaval shunt (PCS; n=15). TNF-alpha, IL-1beta and IL-10 were assayed by ELISA techniques, the expression of the endothelial constitutive nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), constitutive and inducible heme-oxygenase (HO-1 and HO-2) were assayed by Western-blot. mRNA levels of HO-1, HO-2, TNF alpha, IL-1beta and IL-10 were quantified by reverse transcriptase polymerase chain reaction amplification (RT-PCR) in the small bowel, liver, spleen and lungs. Portacaval shunting in the rat produces an interorgan imbalance of pro- and anti-inflammatory mediators. TNF-alpha mRNA expression is decreased in the liver (0.69+/-0.28, p<0.05). The hepatic production of IL-Ibeta (204.13+/-71.90 pg/100 g; p<0.001) and IL-10 (4505.47+/-337.97 pg/100 g; p<0.001) is also decreased. However, the intestinal pro-inflammatory (TNF-alpha: 1471.86+/-153.62 pg/100 g, p<0.001; IL-1beta: 48.35+/-9.84 pg/100 g, p<0.001 and iNOS: 0.59+/ 0.01, p<0.01) and anti-inflammatory (IL-10: 1503.39+/-53.5 pg/100 g, p<0.001 and HO-1: 2.23+/-0.16, p<0.001) mediators are increased. Total portacaval shunting in the rat induces impairments of pro- and anti-inflammatory mediators in the splanchnic-lung axis that could be associated with a multiple organ dysfunction syndrome. Therefore, the complications after portosystemic shunts could be integrated into a systemic inflammatory response of possible intestinal origin. PMID- 21975128 TI - Effects of captopril and angiotensin II receptor blockers (AT1, AT2) on myocardial ischemia-reperfusion induced infarct size. AB - The renin-angiotensin system (RAS) plays a major role in regulating the cardiovascular system, and disorders of the RAS contribute largely to the cardiac pathophysiology, including myocardial ischemia-reperfusion (MI/R) injury. Two subtypes of angiotensin II (Ang II) receptors have been defined on the basis of their differential pharmacological properties. The current study was undertaken to address the question as to whether the inhibition of the angiotensin converting enzyme (ACE) by captopril and the AT1 and AT2 receptor blockers losartan and PD123319 modulate MI/R-induced infarct size in an in vivo rat model. To produce necrosis, a branch of the descending left coronary artery was occluded for 30 min followed by two hours of reperfusion. ECG changes, blood pressure, and heart rate were measured during the experiment. Captopril (3 mg/kg), losartan (2 mg/kg), and PD123319 (20 MUg/kg/min) were given in an IV 10 min before ischemia and were continued during the ischemic period. The infarcted area was measured by TTC staining. The volume of infarct and the risk zone was determined by planimetry. Compared to the control group (55.62+/-4.00%) both captopril and losartan significantly reduced the myocardial infarct size (30.50+/-3.26% and 37.75+/-4.44%), whereas neither PD123319 nor PD123319+losartan affected the infarct size volume (46.50+/-3.72% and 54.62+/-2.43%). Our data indicates that captopril and losartan exert cardioprotective activity after an MI/R injury. Also, infarct size reduction by losartan was halted by a blockade of the AT2 receptor. Therefore, the activation of AT2 receptors may be potentially protective and appear to oppose the effects mediated by the AT1 receptors. PMID- 21975129 TI - Pituitary apoplexy can mimic acute meningoencephalitis or subarachnoid haemorrhage. AB - Pituitary apoplexy is an uncommon but life-threatening condition that is often overlooked and underdiagnosed. We report a 45-year-old man who presented to our emergency department with a sudden onset headache, acute confusion, signs of meningeal irritation and ophthalmoplegia. An initial diagnosis of acute meningoencephalitis was made, which was amended to pituitary apoplexy following thorough investigation within the emergency department.A 45-year-old man was brought to our emergency department by ambulance with a history of sudden onset of frontal headache and acute confusion. His wife provided the history. There was no significant past medical history of diabetes, hypertension, recent travel abroad, exposure to sick contacts, involvement in outdoor pursuits such as hiking/cave diving, or trauma. He worked in a bank and had been well until 24 h prior to the onset of sudden headache, which was gradually worsening in nature and associated with increasing confusion. The patient's wife reported that he had neither experienced any fevers, night sweats, or coryzal symptoms nor received any recent vaccinations. He was not on any regular medications. He was a non smoker and occasionally consumed alcohol. There was no significant family history. On examination in the ED, his temperature was 37.6 degrees C, his pulse was 110/min, and he was normotensive and normoglycaemic. A macular blanching rash was noted over the patient's trunk. The patient was disoriented to time and place. Neurological examination revealed reduced GCS (11/15-E3, M6, V2), marked neck stiffness, a positive Kernig's sign and a right sixth nerve palsy.A provisional diagnosis of acute meningoencephalitis was made and the patient was started on a course of intravenous antibiotics with benzyl penicillin 1.2 g, cefotaxime 2 g and acyclovir 750 mg. Baseline blood investigations revealed hyponatraemia (122 mmol/l), a white-cell count of 11 * 109/l and a C-reactive protein > 250. Due to the sudden onset of the symptoms and lack of prodrome, an urgent CT head scan was performed to rule out a cerebrovascular event. The scan demonstrated an enlarged pituitary gland (3 cm in diameter) with impingement of the optic chiasm. The centre of the enlarged pituitary gland was noted to be hypodense in comparison to its periphery, which was consistent with a diagnosis of pituitary apoplexy. A subsequent MRI confirmed the diagnosis (Figure 1) of an enlarged sella containing abnormal soft tissue with increased signal intensity suggestive of haemorrhage (Figure 1A).Post-MRI a lumbar puncture was performed revealing glucose 3.4 mmol/l, protein 1.0 g/l, red cells of 53/mm3 and white cells of 174/mm3 with predominant neutrophilia. No organisms were seen, and CSF cultures and HSV DNA tests were found to be negative. Endocrinological investigations demonstrated low concentrations of thyroid hormones [TSH: 0.14 mIu/l (0.35-5.5 mlU/l), FT3: 1.1 nmol/l (1.2-3.0 nmol/l), FT4: 9.6 pmol/l (8-22 pmol/l)], gonadal hormones (LH: < 1 u/l) and prolactin: 16 u/l (<450 u/l). Serum FSH was 2.9 u/l (0.8-11.5 u/L) and cortisol 575 nmol/l (450-700 nmol/l). The patient was treated for hypopituitarism based on clinical and radiological findings with intravenous fluids, hydrocortisone (100 mg) and thyroxine (50 MUg) as loading doses in the ED.Within 24 h of commencement of therapy the patient's GCS rose to 15, and within 48 h there was marked improvement in the right sixth cranial nerve palsy. Formal visual field assessment demonstrated temporal visual field loss in the left eye. The patient was discharged to his usual residence a week later and follow-up was organised with both the endocrinologists and ophthalmologists. Follow-up MRI demonstrated that there was no significant change in either size or signal characteristics of the pituitary fossa mass (Figure 1B). PMID- 21975130 TI - Atrial septal defect closure in the elderly is associated with excellent quality of life, functional improvement, and ventricular remodelling. AB - BACKGROUND: While atrial septal defect (ASD) closure is known to improve morbidity and mortality in children and adults, data are only beginning to emerge about its role in elderly cohorts. The goals of this study were to compare outcomes after device or surgical closure of ASDs in the elderly, and to quantitatively assess quality of life. METHODS: Patients>60 years old who underwent ASD repair were studied. Functional status, arrhythmia burden, biventricular size and function were compared before and after ASD closure. Quality of life after ASD closure was assessed with the RAND SF-36 instrument. RESULTS: Sixty-seven patients, mean age of 68 years (range 60-86 years), were followed for 3.3 years. Nineteen percent underwent surgical closure and 81% underwent device closure. Major complication rates were 23% and 7% respectively with no procedure- related deaths. After surgical and device closure, quality of life was comparable to age-matched healthy controls, right ventricular end diastolic dimension decreased by 10 mm (P<0.001), left ventricular end-diastolic dimension increased by 4 mm (P=0.001), biventricular function improved (right ventricular, P<0.001; left ventricular, P=0.007) and New York Heart Association class improved (P<0.001). Prevalence of atrial arrhythmias however, was unchanged. Beneficial effects were similar for patients treated surgically or with device closure. CONCLUSIONS: Given the favorable structural, functional, and quality of life outcomes after ASD closure in the elderly, advanced age alone should not be a contraindication to recommending surgical or device closure of an ASD. PMID- 21975131 TI - Giant left ventricular aneurysm mimicking myocardial bridge. AB - An 81-year-old woman was admitted due to acute pulmonary edema. The electrocardiogram showed new Q-waves in anterior leads with ST-elevation in anterolateral leads. Coronary angiogram showed a 100% occluded second diagonal branch with an image of systolic and diastolic compression of the mid-to-distal portion of the left anterior descending coronary artery (LAD) causing a long "bridgelike" effect. Ventriculography revealed a giant aneurysm of the anterolateral wall. A 3-dimensional volume-rendered cardiac computed tomography scan suggested that the aneurysm produced extrinsic compression of the LAD. PMID- 21975132 TI - REFLEX, a social-cognitive group treatment to improve insight in schizophrenia: study protocol of a multi-center RCT. AB - BACKGROUND: Insight is impaired in a majority of people with schizophrenia. Impaired insight is associated with poorer outcomes of the disorder. Based on existing literature, we developed a model that explains which processes may possibly play a role in impaired insight. This model was the starting point of the development of REFLEX: a brief psychosocial intervention to improve insight in schizophrenia. REFLEX is a 12-sessions group training, consisting of three modules of four sessions each. Modules in this intervention are: "coping with stigma", "you and your personal narrative", and "you in the present". METHODS/DESIGN: REFLEX is currently evaluated in a multicenter randomized controlled trial. Eight mental health institutions in the Netherlands participate in this evaluation. Patients are randomly assigned to either REFLEX or an active control condition, existing of cognitive remediation exercises in a group. In a subgroup of patients, fMRI scans are made before and after training in order to assess potential haemodynamic changes associated with the effects of the training. DISCUSSION: REFLEX is one of the few interventions aiming specifically to improving insight in schizophrenia and has potential value for improving insight. Targeting insight in schizophrenia is a complex task, that comes with several methodological issues. These issues are addressed in the discussion of this paper. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN50247539. PMID- 21975133 TI - Biblio-MetReS: a bibliometric network reconstruction application and server. AB - BACKGROUND: Reconstruction of genes and/or protein networks from automated analysis of the literature is one of the current targets of text mining in biomedical research. Some user-friendly tools already perform this analysis on precompiled databases of abstracts of scientific papers. Other tools allow expert users to elaborate and analyze the full content of a corpus of scientific documents. However, to our knowledge, no user friendly tool that simultaneously analyzes the latest set of scientific documents available on line and reconstructs the set of genes referenced in those documents is available. RESULTS: This article presents such a tool, Biblio-MetReS, and compares its functioning and results to those of other user-friendly applications (iHOP, STRING) that are widely used. Under similar conditions, Biblio-MetReS creates networks that are comparable to those of other user friendly tools. Furthermore, analysis of full text documents provides more complete reconstructions than those that result from using only the abstract of the document. CONCLUSIONS: Literature based automated network reconstruction is still far from providing complete reconstructions of molecular networks. However, its value as an auxiliary tool is high and it will increase as standards for reporting biological entities and relationships become more widely accepted and enforced. Biblio-MetReS is an application that can be downloaded from http://metres.udl.cat/. It provides an easy to use environment for researchers to reconstruct their networks of interest from an always up to date set of scientific documents. PMID- 21975134 TI - Sociodemographic and psychopathological risk factors in repeated suicide attempts: gender differences in a prospective study. AB - BACKGROUND: The prevention of the repetition of suicide attempts is an important feature of the care of attempters but current data fail to give actual predictors of repetition. The aim of this study was to characterize sociodemographic and psychopathological features and risk factors associated with future repetition of suicide attempts in two years. The study focused on differences between men and women. METHODS: 273 participants selected in psychiatric emergency units after their admission for a suicide attempt (index) were included in the study. Subsequent suicide attempts occurring within a two year follow-up were identified from the regional observatory of suicide attempts. At inclusion, sociodemographic variables and psychopathological data were collected. In particular, psychometric evaluations were performed using the following scales: BDI-SF, SIS, BIS and BDHI. The lifetime history of suicide attempt was also noted. RESULTS: Repetition of suicide attempt in 2 years was associated with current follow up and treatment, a personal history of multiple suicide attempt, post traumatic stress disorder, current recurrent psychotic syndrome and substance misuse. Specific features of men and women repeaters have been identified. Men repeaters were characterized by substance use disorders whereas the re-attempt in women was associated with current follow up and treatment, post traumatic stress disorder and higher BDI-SF score. CONCLUSIONS: Repeaters must be considered as a specific population among suicide attempters and gender differences must be taken into account in this particular population in order to promote more personalized prevention programs for suicidal recurrence and completed suicide. PMID- 21975135 TI - Impact on prisoners of participating in research interviews related to near lethal suicide attempts. AB - BACKGROUND: Prisoners have a high risk of suicide. Research studies have investigated factors contributing to this, some through interviews with survivors of suicide attempts, others with informants such as family and friends of suicide victims. However, there is little information regarding the effects of participating in such interviews. AIMS: To investigate the effects on participants of taking part in detailed interviews about suicidal behaviour and contributory factors. METHOD: Case-control studies of 120 prisoners who made near lethal suicide attempts (cases) and 120 prisoners who had never carried out near lethal suicide attempts in prison (controls) were conducted. Information regarding effects on prisoners of participating in the interviews was collected using quantitative and qualitative methods. RESULTS: For both male cases and controls, and female controls, self-reported mood levels improved significantly by the end of the interviews. For female cases, the interviews had no negative effect on their self-reported mood. Whilst some prisoners found the interviews upsetting, nearly all said they were pleased to have participated. LIMITATIONS: The same researchers carried out the interviews and collected data on the effects of participation. Also, several potential participants were excluded from the study and the likely effect of the interview on them is unknown. CONCLUSIONS: We found little evidence that participation of prisoners in interview-based research on suicidal behaviour has negative effects on them; indeed, it can be beneficial. Inclusion of similar instruments to measure the effects of research participation in future investigations could provide valuable feedback to researchers and ethics committees. PMID- 21975136 TI - Long-term impact of the life goals group therapy program for bipolar patients. AB - BACKGROUND: Psychoeducation added to biological treatment enhances overall effectiveness in bipolar disorders. Here, we evaluated the long-term impact of a 2-phase structured psycho-educative group program (Life Goals Program or LGP) for bipolar patients, on parameters such as number and length of hospitalizations, mood stability, relapse prevention and social relationships. METHODS: Eighty-five patients (55 females, 30 males) with bipolar disorder (48 bipolar I, 37 bipolar II) were included retrospectively. Fifty patients participated in phase 1 and 35 participated in phases 1 and 2 of the LGP. Impact on the number and cumulative length of hospitalization was evaluated by comparing the 3-year period before and after participation in phase 1 (6 weeks) or phases 1 and 2 (median duration 24 months, range 3-74). RESULTS: Number of hospitalizations significantly decreased from the 3-year period before to the 3-year period after participation in phase 1 only (p=0.017), as well as participation in both phases (p=0.035). After attending phase 1 or phases 1 and 2, a majority of participants reported subjective improvement in mood stability, efficient prevention of relapse and better coping with relapse. Perceived improvement of social relationships was significantly higher for patients who attended phases 1 and 2 than for participants in phase 1 only. LIMITATIONS: Uncontrolled retrospective study design. CONCLUSIONS: Results suggest that both phase 1 only and the full 2-phase LGP have long-term positive effects on the number of hospitalizations, mood stability and relapse prevention. PMID- 21975137 TI - Developing a clinical typology of dysfunctional anger. AB - BACKGROUND: This study attempted to validate a clinical typology of dysfunctional anger proposed by DiGiuseppe and Tafrate (2007) using assessment data obtained from 197 participants assessed at an outpatient clinic for anger problems. METHODS: Several self-report scales assessing anger, hostility, impulsivity and aggression, as well as a structured interview regarding anger experience and expression, were administered; Axis I and II comorbidity were assessed using clinical assessment and the SCID-II PQ. RESULTS: We found support for four of the proposed eight types described by DiGiuseppe and Tafrate - Pervasive Dysfunctional Anger, Impulsive Type; Pervasive Dysfunctional Anger, Mixed Type; Impulsive Aggressive Dysfunctional Anger; and Suppressed Dysfunctional Anger - with significant, predicted group differences on self-report measures of anger, aggression, and impulsivity, as well as differences in Axis I and II diagnoses. LIMITATIONS: Patients were rarely assigned to the other four dysfunctional anger types and thus we could not examine the validity of these types. We relied heavily on self-report data. CONCLUSIONS: Anger is a common symptom in outpatient psychiatry clinics. It is associated with both mood and anxiety disorder diagnoses, and often co-occurs with substance use problems. Different types of angry patients will likely require different assessment and treatment approaches. PMID- 21975138 TI - Young people's beliefs about preventive strategies for mental disorders: findings from two Australian national surveys of youth. AB - BACKGROUND: Political interest in prevention of mental illness has increased in recent years. However, relatively little is known about the public's beliefs about prevention, and the predictors of these beliefs. Since many disorders start in the first decades of life, a focus on young people is warranted. METHODS: Young people's prevention beliefs were assessed by a national telephone survey of 3746 Australian youths aged 12-25 years in 2006. A similar survey was repeated in 2011 with 3021 youths aged 15-25. In both surveys, respondents were presented with a vignette portraying depression, psychosis, social phobia, or depression with alcohol abuse in a young person. The 2011 survey also included depression with suicidal thoughts and post-traumatic stress disorder. Respondents rated the helpfulness of seven potential prevention strategies, and reported on any experience of mental health problems and treatment in the past year, exposure to beyondblue and mental health information at school or work. RESULTS: Most respondents believed that regular contact with friends and family and regular physical activity would be helpful. Respondents who had recently experienced mental health problems, younger respondents, females, and those not exposed to beyondblue or mental health information were more likely to hold beliefs that differed from those of health professionals or available evidence. No significant changes were observed between surveys. LIMITATIONS: Actual preventive actions and reasons behind respondents' beliefs were not assessed. CONCLUSIONS: Future prevention efforts should target subgroups with beliefs that differ from professionals' and research evidence. Beyondblue and school and work settings may be promising avenues for these efforts. PMID- 21975139 TI - Combined anxiety and depressive symptoms before diagnosis of breast cancer. AB - PURPOSE: To determine the relationship between pre-diagnosis state anxiety, depressive symptoms, and combined state anxiety and depressive symptoms (CADS) with quality of life (QOL), fatigue, state anxiety and depressive symptoms one and two years after surgery in women with breast cancer. METHODS: Women with breast problems referred to a Dutch outpatient clinic were recruited for the study. Participants (N=428) completed a set of questionnaires before diagnosis (Time0) and the women with breast cancer subsequently received questionnaires at 12 (Time1) and 24 months (Time2) after surgical treatment. The questionnaire set consisted of questionnaires on demographics, state anxiety, depressive symptoms, fatigue, QOL, neuroticism, and trait anxiety. Chi-square tests, independent samples T-tests, and multivariate linear regression analyses were used to do the analyses. RESULTS: Before their diagnosis of breast cancer, 111 women (28%) had CADS. Of the CADS-group, a higher percentage had elevated levels of anxiety, depressive symptoms, and CADS at all follow-up moments than of the non-CADS group. CADS-score at before diagnosis and neuroticism were the most important predictors of outcome measures at Time1 and Time2. CONCLUSIONS: More than one in four women, who later received the diagnosis breast cancer, had elevated levels of both state anxiety and depressive symptoms (CADS) just before diagnosis. This factor was also a major predictor of QOL, state anxiety, depressive symptoms, and fatigue 12 and 24 months after surgery. This implies that women with a higher score on both state anxiety and depressive symptoms should be identified as soon as possible in the process of diagnosis and treatment of breast cancer using validated questionnaires or screening instruments. Only by identifying this group of patients, tailored psychological care can be accomplished. PMID- 21975140 TI - Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): increased interleukin-1, tumor necrosis factor-alpha, PMN-elastase, lysozyme and neopterin. AB - BACKGROUND: There is evidence that inflammatory pathways and cell-mediated immunity (CMI) play an important role in the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Activation of inflammatory and CMI pathways, including increased levels of cytokines, is known to induce fatigue and somatic symptoms. Given the broad spectrum inflammatory state in ME/CFS, the aim of this study was to examine whether inflammatory and CMI biomarkers are increased in individuals with ME/CFS. METHODS: In this study we therefore measured plasma interleukin-(IL)1, tumor necrosis factor (TNF)alpha, and PMN-elastase, and serum neopterin and lysozyme in 107 patients with ME/CFS, 37 patients with chronic fatigue (CF), and 20 normal controls. The severity of ME/CFS was measured with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale. RESULTS: Serum IL-1, TNFalpha, neopterin and lysozyme are significantly higher in patients with ME/CFS than in controls and CF patients. Plasma PMN-elastase is significantly higher in patients with ME/CFS than in controls and CF patients and higher in the latter than in controls. Increased IL 1 and TNFalpha are significantly correlated with fatigue, sadness, autonomic symptoms, and a flu-like malaise; neopterin is correlated with fatigue, autonomic symptoms, and a flu-like malaise; and increased PMN-elastase is correlated with concentration difficulties, failing memory and a subjective experience of infection. CONCLUSIONS: The findings show that ME/CFS is characterized by low grade inflammation and activation of CMI. The results suggest that characteristic symptoms of ME/CFS, such as fatigue, autonomic symptoms and a flu-like malaise, may be caused by inflammatory mediators, e.g. IL-1 and TNFalpha. PMID- 21975141 TI - Genotyping of selected bacterial enteropathogens in Norway. AB - In Norway the Norwegian Institute of Public Health (NIPH) is the primary facility for nationwide surveillance of foodborne infections, and it is vital that we can perform rapid and high resolution identification of foodborne bacteria at the strain level. During the last decade a rapid introduction of DNA-based methods has been introduced, which show promise in enhancing the speed and discriminatory capability of the typing laboratory. The laboratory responsible for genotyping enteropathogens at NIPH is limited in staff, thus methods demanding reduced labour, high degree of automation and increased ease of interpretation is essential. We found that this could be achieved by focusing on MLVA for some of the most predominant enteropathogenic species. Bacterial genotyping is performed by several laboratories in Norway, however this review will address the use of routine genotyping by MLVA of common foodborne bacteria at NIPH. The emphasis will be on Escherichia coli, Salmonella typhimurium, Shigella spp. Yersinia enterocolitica and Listeria monocytogenes. This review is based on an oral presentation given at the 9th International Meeting on Microbial Epidemiological Markers in Wernigerode Germany on September 1st 2010. PMID- 21975142 TI - The correlation between subordinate fish eye colour and received attacks: a negative social feedback mechanism for the reduction of aggression during the formation of dominance hierarchies. AB - Eye darkening has been linked to social status in fish. The subordinate's eyes darken, while the eyes of the dominant fish become pale. Although this phenomenon has been described in salmonid fishes and in the African cichlid Nile tilapia Oreochromis niloticus, it is unclear whether eye darkening correlates with a reduction in aggressive behaviour. Thus, we evaluated the link between social status and eye darkening. We evaluated whether the eye colours of subordinate fish correlate with the frequency of received attacks in a neotropical fish, the pearl cichlid Geophagus brasiliensis. We paired pearl cichlids and quantified both the aggressive behaviour and the eye darkening of each fish. As has been described for Nile tilapia and Atlantic salmon, a clear-cut hierarchical relationship formed, where dominance and subordination were associated with pale and dark eye colours, respectively. Initially, eye colour darkening was positively correlated with the frequency of received attacks; however, a negative association occurred following eye darkening, in which the intensity of aggressive interactions decreased. Thus, fish that initially received a high number of attacks signalled subordination more rapidly and intensely (rapid and dramatic eye darkening), thereby inducing a negative social feedback mechanism that led to reduced aggression. PMID- 21975143 TI - Variation of the Fourier transform mass spectra phase function with experimental parameters. AB - It has been known for almost 40 years that phase correction of Fourier transform ion cyclotron resonance (FTICR) data can generate an absorption-mode spectrum with much improved peak shape compared to the conventional magnitude-mode. However, research on phasing has been slow due to the complexity of the phase wrapping problem. Recently, the method for phasing a broadband FTICR spectrum has been solved in the MS community which will surely resurrect this old topic. This paper provides a discussion on the data processing procedure of phase correction and features of the phase function based on both a mathematical treatment and experimental data. Finally, it is shown that the same phase function can be optimized by adding correction factors and can be applied from one experiment to another with different instrument parameters, regardless of the sample measured. Thus, in the vast majority of cases, the phase function needs to be calculated just once, whenever the instrument is calibrated. PMID- 21975144 TI - Cytology-based treatment decision in primary lung cancer: is it accurate enough? AB - Accurate distinction of lung cancer types has become increasingly important as recent trials have shown differential response to chemotherapy among non-small cell lung carcinoma (NSCLC) subtypes. Cytological procedures are frequently used but their diagnostic accuracy has been previously questioned. However, new endoscopic and cytological techniques might have improved cytological accuracy in comparison with prior findings. The aim of this study was to reassess cytological accuracy for diagnosis of lung cancer subtypes. A retrospective chart review of subjects who underwent fiberoptic bronchoscopy (FOB) for suspicion of lung cancer in 2007-2008, was undertaken. Reports of bronchoscopically derived cytological specimens were compared to those of histological material. Endoscopic findings and specific investigational techniques were taken into account. A total of 467 FOB with both cytological and histological diagnostic techniques were performed in 449 subjects. Patients consisted of 345 men and 104 women (median age, 65 yrs). Cytology proved malignancy in 157 patients. Cytologically diagnosed carcinomas were classified into squamous cell carcinoma (SqCC) in 56, adenocarcinoma (ADC) in 6, small cell lung carcinoma (SCLC) in 12, non-small cell lung carcinoma not otherwise specified (NSCLC-NOS) in 71, and unclassified carcinoma in 12. Cytology correlated fairly with biopsy specimens, as agreement was observed in 83% of SCLC, 100% of ADC, 74% of SqCC and 8% of NSCLC-NOS. Interestingly, 61% of cytologically identified NSCLC-NOS were classified as ADC by histology. Cytological accuracy improved in case of an endobronchial lesion, mainly for SqCC. These results indicate that cytological accuracy remains fair with regard to diagnosis of squamous and non-squamous lung cancer subtypes. Improvement of cytological accuracy is expected however with novel diagnostic strategies. PMID- 21975146 TI - Omalizumab. An option in vernal keratoconjunctivitis? PMID- 21975145 TI - Heated indoor swimming pools, infants, and the pathogenesis of adolescent idiopathic scoliosis: a neurogenic hypothesis. AB - BACKGROUND: In a case-control study a statistically significant association was recorded between the introduction of infants to heated indoor swimming pools and the development of adolescent idiopathic scoliosis (AIS). In this paper, a neurogenic hypothesis is formulated to explain how toxins produced by chlorine in such pools may act deleteriously on the infant's immature central nervous system, comprising brain and spinal cord, to produce the deformity of AIS. PRESENTATION OF THE HYPOTHESIS: Through vulnerability of the developing central nervous system to circulating toxins, and because of delayed epigenetic effects, the trunk deformity of AIS does not become evident until adolescence. In mature healthy swimmers using such pools, the circulating neurotoxins detected are chloroform, bromodichloromethane, dibromochloromethane, and bromoform. Cyanogen chloride and dichloroacetonitrile have also been detected. TESTING THE HYPOTHESIS: In infants, the putative portals of entry to the blood could be dermal, oral, or respiratory; and entry of such circulating small molecules to the brain are via the blood brain barrier, blood-cerebrospinal fluid barrier, and circumventricular organs. Barrier mechanisms of the developing brain differ from those of adult brain and have been linked to brain development. During the first 6 months of life cerebrospinal fluid contains higher concentrations of specific proteins relative to plasma, attributed to mechanisms continued from fetal brain development rather than immaturity. IMPLICATIONS OF THE HYPOTHESIS: The hypothesis can be tested. If confirmed, there is potential to prevent some children from developing AIS. PMID- 21975147 TI - The interest of FEF(25-75) in evaluating bronchial hyperresponsiveness with the methacholine test. AB - BACKGROUND: Bronchial hyperresponsiveness is the pathogenic basis of asthma, and measurement of its intensity is investigated using the methacholine provocation test, which not only and particularly evaluates the reduction in FEV1 (PD20) but also takes forced mid-expiratory flow or FEF(25-75) (PD40) into account. The present study aims to evaluate the usefulness of both parameters. MATERIAL AND METHODS: Provocation testing was carried out in 151 patients between 7 and 22 years of age diagnosed with asthma, tracheobronchitis and/or rhinitis, using a short method that allows quantification of the methacholine administered. The subjects were divided into three groups according to the amount of methacholine needed to obtain the mentioned parameters (group 1: <=1000MUg; group 2: 1001 2000MUg; group 3: >=2001MUg). RESULTS: Greater variability was recorded for FEF(25-75) than for FEV1. Paired comparison among the three groups for FEV1 proved significant, in the same way as for FEF(25-75) between groups 2 and 3, and 1 and 3, but not between groups 1 and 2. Calculation was made of the amount of methacholine required to obtain PD20 and PD40 from the same dose. Only the significant differences corresponded to the comparison of group 1 versus the rest, with no differences between the means of the total mean values. CONCLUSIONS: The utility of PD20 is more evident, considering the variability of PD40; the latter may be useful in patients with rhinitis or tracheobronchitis when PD20 proves scantly demonstrative. PMID- 21975148 TI - A randomized controlled study investigating static and dynamic balance in older adults after training with Pilates. AB - OBJECTIVE: To evaluate effects of a Pilates intervention on balance and function in community-dwelling older (aged >60y) adults. DESIGN: Randomized crossover study design lasting 16 weeks. SETTING: University exercise clinic. PARTICIPANTS: Ambulatory older community-dwelling adults (N=32) were recruited, and 27 (mean +/ SD age, 67.3+/-6.5y) completed the program. INTERVENTION: Participants were allocated to either 5 weeks of a group Pilates training intervention or 5 weeks of usual activity (control). After a 6-week washout period, participants performed the alternate intervention. MAIN OUTCOME MEASURES: Static and dynamic balance measures (mediolateral sway range, Four Square Step Test, Timed Up and Go Test) and leg strength were recorded at 4 times before and after each intervention (baseline [t1], interim time immediately after the first group intervention [t2], after 5-week washout [before the second intervention period] [t3], and at study conclusion after the second group intervention [t4]). RESULTS: There were no significant differences between the Pilates and control groups for any measured variables (P>.05) despite static and dynamic balance significantly improving during the study and from pre- to post-Pilates (P<.05) without significant changes occurring during the control phase. Improvements that occurred during Pilates between t1 and t2 did not return to baseline after the washout period (t3). There were no changes in leg strength. Mediolateral sway range standing on a foam cushion with eyes closed improved -1.64cm (95% confidence interval, -2.47 to -0.82) and had the largest effect size post-Pilates (d=.72). CONCLUSIONS: Although there were no significant between-group differences, participation in the Pilates component of the study led to improved static and dynamic balance. The absence of differences between conditions may be a result of small sample size or the crossover study design because Pilates may produce neuromuscular adaptations of unknown resilience. PMID- 21975149 TI - The use of triage in Danish emergency departments. AB - INTRODUCTION: The emergency departments (EDs) handle approximately 1,000,000 contacts annually. Danish health care is undergoing reorganization that involves the creation of fewer and larger EDs to handle these contacts. There is therefore a need to prioritize the use of resources to optimize treatment. We thus wanted to investigate if Danish EDs are using triage systems and, if so, which systems they are using. MATERIAL AND METHODS: We performed a cross-sectional study on triage at all EDs in the 20 Danish hospitals that have been designated for emergency care. RESULTS: The response rate was 100% (n = 20). We found that triage was used at 75% (n = 15) of the EDs. Adaptive process triage (ADAPT) was the most frequently used validated triage system (25% (n = 5)), while 40% (n = 8) used non-validated systems. Triage was performed by nurses at 73% (n = 11) of the EDs using triage. CONCLUSION: Triage systems were used in 75% of Danish EDs. ADAPT was the primary triage system in 25% of the EDs, while 40% used non validated triage systems. An improvement in the quality of health care in Danish EDs may possibly be achieved by implementing validated triage, i.e. ADAPT. FUNDING: not relevant. TRIAL REGISTRATION: not relevant. PMID- 21975150 TI - Patient-reported outcome of hip resurfacing arthroplasty and standard total hip replacement after short-term follow-up. AB - INTRODUCTION: The purpose of this study was to investigate patient-reported outcome in terms of satisfaction in two study groups that had undergone hip resurfacing arthro-plasty (HRA) or total hip replacement (THR). The procedure consists of placing a hollow, mushroom-shaped metal cap over the femoral head while a matching metal cup is placed in the acetabulum (pelvis socket). MATERIAL AND METHODS: The two study groups included a total of 84 patients with an average age of 57 years who had idiopathic hip osteoarthritis or secondary arthritis based on mild dysplasia with arthritis. A descriptive cross-sectional design was used. A patient-reported questionnaire was used to evaluate patient outcome three years after hip surgery. RESULTS: The study showed that both groups (HRA and THR) reported high levels of overall satisfaction, with 97% and 93% being very satisfied or satisfied. Men were more satisfied with their ability to walk longer distances than women (p < 0.05) and the THR group claimed to be treating their artificial hip with more caution than the HRA group (p < 0.05). CONCLUSION: The choice of prosthesis (HRA or THR) does not appear to affect the overall satisfaction or patient-perceived functional outcome three years after surgery in patients who on average were 57 years old and who had idiopathic hip osteoarthritis or secondary arthritis based on mild dysplasia. FUNDING: A number of the patients included in this study were enrolled in a randomized controlled trial that was financially supported by Protesekompagniet. Furthermore, Centre for Applied Health Services Research and Technology Assessment (CAST) has paid wages in the preparation of the qualitative aspect of the research. TRIAL REGISTRATION: The survey was not registered at Clinical Trials because the starting point for this study was a health technology assessment report based on a randomized controlled trial (RCT). This RCT was registered at Clinical Trials with the identification number NCT01113762. The patient population was partly taken from this RCT and partly from an earlier pilot study conducted at Odense University Hospital. The present study was registered at the Danish Data Protection Agency, registration number 2010-41-5661. PMID- 21975151 TI - Nurses' evaluation of a new formalized triage system in the emergency department a qualitative study. AB - INTRODUCTION: Formalized triage in the emergency department (ED) is not widely used in Denmark; this study explores the effects of introducing a five-level process triage system in a Danish ED. MATERIAL AND METHODS: Semi-structured qualitative interviews were conducted with 15 emergency nurses. The interviews were preceded by observations of the work of the ED nurses in which focus was on the triage process. RESULTS: Formalized triage was experienced to improve the overview of patients and resources at the ED, and the nurses described that they felt more assured when prioritizing between patients. Communication and coordination were also improved by the triage system. But more time spent on documentation and reevaluation may cause the nurses to feel professionally inadequate if adequate resources are not provided. Furthermore, the triage system has reduced the focus on the humanistic and psychosocial aspects of nursing. Difficulties were occasionally experienced when categorizing patients with diffuse symptoms according to the standardized triage symptoms and signs' algorithms. CONCLUSION: Introducing a formalized triage system in the ED was experienced to give a better overview and more overall control of ED patients. Adequate resources are needed to ensure that a stronger focus on documentation and re-evaluation related to triage does not produce a feeling of professional inadequacy among the staff. FUNDING: not relevant. TRIAL REGISTRATION: not relevant. PMID- 21975152 TI - Five easy equations for patient flow through an emergency department. AB - INTRODUCTION: Queue models are effective tools for framing management decisions and Danish hospitals could benefit from awareness of such models. Currently, as emergency departments (ED) are under reorganization, we deem it timely to empirically investigate the applicability of the standard "M/M/1" queue model in order to document its relevance. MATERIAL AND METHODS: We compared actual versus theoretical distributions of hourly patient flow from 27,000 patient cases seen at Frederiksberg Hospital's ED. Formulating equations for arrivals and capacity, we wrote and tested a five equation simulation model. RESULTS: The Poisson distribution fitted arrivals with an hour-of-the-day specific parameter. Treatment times exceeding 15 minutes were well-described by an exponential distribution. The ED can be modelled as a black box with an hourly capacity that can be estimated either as admissions per hour when the ED operates full hilt Poisson distribution or from the linear dependency of waiting times on queue number. The results show that our ED capacity is surprisingly constant despite variations in staffing. These findings led to the formulation of a model giving a compact framework for assessing the behaviour of the ED under different assumptions about opening hours, capacity and workload. CONCLUSION: The M/M/1 almost perfectly fits our. Thus modeling and simulations have contributed to the management process. FUNDING: not relevant. TRIAL REGISTRATION: not relevant. PMID- 21975153 TI - Nationwide analysis of prolonged hospital stay and readmission after elective ventral hernia repair. AB - INTRODUCTION: Early outcome after elective ventral hernia repair is unsatisfactory, but detailed analyses are lacking. The aim of this study was to describe the aetiology of prolonged hospital stay (LOS), readmission and death < 30 days after elective ventral hernia repair. MATERIAL AND METHODS: The present study was a nationwide case-control study based on prospective results from elective ventral hernia repairs (incisional, umbilical/epigastric, parastomal and other rare ventral hernia repairs) performed in Denmark during 2008. The exclusion criteria were emergency operation and ventral hernia repair in addition to another surgical procedure. The study group were patients with poor outcome (a LOS >= 5 days and/or readmission and/or death <= 30 days) and the control group were patients without a poor outcome. Major complications were defined as severe and potentially fatal complications. RESULTS: The cohort included 2,258 patients (a study group counting 258 patients (259 repairs) and a control group comprising 2,000 patients (2,016 repairs)). Patients in the study group underwent repair significantly more often for incisional (76% versus 28%, p < 0.001), parastomal (3% versus 1%, p = 0.001) and recurrent hernia (21% versus 12%, p < 0.001). Furthermore, hernia defects were significantly larger (median 8 cm versus 2 cm, p < 0.001) in the study group than in the control group. Prolonged LOS was mainly due to pain (27%), major complications (19%), and seroma formation (9%). Readmissions were primarily caused by wound infections and pain. CONCLUSION: Readmissions and prolonged hospital stay after ventral hernia repair were mainly due to pain, major complications, wound infections and seroma formation. FUNDING: The foundation of Engineer Johs. E. Ormstrup and wife Grete Ormstrup and Region Zealand"s foundation for health-care research provided funding for this study. TRIAL REGISTRATION: The study was registered with the Danish Data Protection Agency (ref. no. 2008-58-0020) and www.clinicaltrials.gov (ref. no. NCT01388634). PMID- 21975154 TI - Outstanding challenges for rotavirus vaccine introduction in low-income countries -a systematic review. AB - Rotavirus infections are the most common cause of severe diarrhoea in children worldwide. Two internationally licensed rotavirus vaccines have proven to be efficacious in middle and high-income countries and they could potentially be valuable tools for the prevention of rotavirus-associated diarrhoea in low-income countries where the disease burden is greatest. However, before the vaccines can be introduced into the national immunisation programmes in these countries, many challenges related to the financing of vaccine purchase, the cold chain capacity and vaccine efficacy must be overcome. There is also a need for political commitment to prevent rotavirus infections as well as a need for an overall strengthening of the health systems in low-income countries. If these challenges were met, rotavirus vaccination could substantially improve child health and survival from rotavirus-associated diarrhoea. PMID- 21975155 TI - Screening for fall risk in the elderly in the capital region of Copenhagen: the need for fall assessment exceeds the present capacity. AB - INTRODUCTION: As falls in the elderly are a major problem, the Danish National Board of Health recommends systematic screening of 65+ year-olds who visit an emergency department following a fall. MATERIAL AND METHODS: As part of a fall prevention programme, screening for fall risk was carried out in four different settings where health staff meets elderly fallers. All falls were recorded and patients interviewed. RESULTS: A total of 2,016 falls were registered. Among these, 1,074 were accidental episodes of which 413 occurred in elderly patients with good balance. There were significant differences between the various screening locations. Need for fall prevention ranged from 50% to 84%. Elderly who were cognitively or physically impaired and elderly with abuse issues fell frequently and a need for fall preventive actions was observed in up to two of three falls in this subgroup of elderly. CONCLUSION: The study shows that the need for fall prevention is considerable and that the estimated need for fall prevention far exceeds the capacity of geriatric fall clinics. As the number of elderly will increase in coming years, it should be explored to which extent recommendations concerning identification and assessment of elderly fallers are followed and whether recommendations result in fall preventive actions. FUNDING: The project was supported by the Ministry of Interior and Health and by The Fund for Scientific Work in the Geriatric Field within the former Copenhagen Hospital Corporation. TRIAL REGISTRATION: not relevant. PMID- 21975156 TI - Lack of consensus between general practitioners and official guidelines on alcohol abstinence during pregnancy. AB - INTRODUCTION: Many pregnant women in Denmark have been advised that some alcohol intake is acceptable. In the 1999-2007-period, the Danish National Board of Health advised pregnant women that some alcohol intake was acceptable. From 2007, alcohol abstinence has been recommended. We aimed to describe the attitudes towards and knowledge about alcohol in pregnancy among general practitioners (GPs) in Denmark in 2000 and in 2009. MATERIAL AND METHODS: In 2000, we invited a representative sample of GPs in the catchment area of the Antenatal Care Centre in Aarhus to participate in the study. Participants were interviewed about their attitudes, beliefs, knowledge and information practice in relation to alcohol in pregnancy. Identical questions were sent to all GPs in the area in 2009. RESULTS: In 2000, most GPs (71%) considered that some alcohol intake in pregnancy was acceptable, mostly on a weekly level. There was considerable interperson variation in the participants' attitudes and recommendations to pregnant women. In 2009, significantly more GPs (51%) considered abstinence to be preferable, and significantly more GPs (53%) gave this advice to pregnant women than in 2000. Their knowledge about the official recommendations on alcohol was good. Older GPs were more likely to recommend abstinence. CONCLUSION: The attitudes towards and knowledge about drinking in pregnancy among GPs have changed along with the change in official policy. FUNDING: In 2000, data collection was funded by The Danish National Board of Health (J.no. 407-15-1999). TRIAL REGISTRATION: not relevant. PMID- 21975157 TI - Gait and postural instability in Parkinson's disease treated with deep brain stimulation of the subthalamic nucleus. AB - In late stage Parkinson's disease (PD), medical treatment may not control the symptoms adequately, and the patient may become eligible for bilateral high frequency deep brain stimulation (DBS) in the subthalamic nucleus (STN). The effect of STN DBS on gait and postural instability is not always as predictable as the effect on clinical symptoms tremor, rigidity and bradykinesia. This may relate to the type of gait disorder or the stimulating electrode localization in the STN. We sought to evaluate the effect of STN DBS on gait performance during overground walking and gait initiation--assessed with 3D optokinetic movement analyses--and to compare the DBS effect with stimulation site localized on peri operative MRI. The stimulation sites were grouped according to STN borders visualised on pre-operative MRI, and the active stimulation site was compared with clinical improvement and gait parameters. STN DBS is associated with improved movement amplitude while movement duration may be unaffected by both disease and stimulation. This may imply an improvement primarily on hypokinesia including gait hypokinesia. PMID- 21975158 TI - Migrants' access to healthcare. AB - There are strong pragmatic and moral reasons for receiving societies to address access to healthcare for migrants. Receiving societies have a pragmatic interest in sustaining migrants' health to facilitate integration; they also have a moral obligation to ensure migrants' access to healthcare according to international human rights principles. The intention of this thesis is to increase the understanding of migrants' access to healthcare by exploring two study aims: 1) Are there differences in migrants' access to healthcare compared to that of non migrants? (substudy I and II); and 2) Why are there possible differences in migrants' access to healthcare compared to that of non-migrants? (substudy III and IV). The thesis builds on different methodological approaches using both register-based retrospective cohort design, cross-sectional design and survey methods. Two different measures of access were used to explore differences: 1) cancer stage at diagnosis as a clinical outcome and 2) emergency room (ER) contacts as a utilisation measure. Both informal and formal barriers to access were studied to explore why possible differences existed including: 1) motivation for using ER; and 2) asylum seekers' healthcare entitlements. Different definitions of migration and ethnicity were investigated including: country of birth and residence status. Substudy I showed a tendency towards more advanced stage at diagnosis or unknown stage among most subgroups of migrant women with a history of cancer compared to non-migrant women. Sub-study II found that some migrants (those born in Somalia, Turkey and Ex-Yugoslavia) use ER services more frequently than do non-migrants whereas others have the same or lower utilisation levels. As a consequence, substudy III was undertaken, which documented that more migrant within all subgroups had considered contacting a primary caregiver before visiting the ER compared to non-migrants, but that migrants experienced communication problems herein. Additionally, more migrants had irrelevant ER visits as evaluated by caregivers. Substudy IV addressed formal and informal barriers to access and screening. According to the law asylum seekers are entitled to emergency care only in 10 out of 24 countries. Medical screening was carried out in all but one of the 24 EU countries; however, the content and extent of screening programmes vary. The thesis aimed to explore if there are differences in migrants' access to healthcare compared to that of non-migrants. Differences in utilisation and clinical outcome were identified between migrants and non-migrants. Reasons why disparities exist were also identified in relation to communication with primary care and on policy level. The thesis shows that various perspectives and scientific problems are important to get a full understanding of the process of access to healthcare for different migrant groups. Moreover, various complementary methodological approaches are needed when studying problems of migrants' access to healthcare. PMID- 21975159 TI - Diagnosis and treatment of fistulising Crohn's disease. AB - A fistula is defined as a pathological connection between the intestine and an inner (bladder or other intestine) or outer (vagina or skin) epithelial surface. Fistulas are discovered in up to 25% of all Crohn's disease patients during long term follow-up examinations. Most are perianal fistulas, and these may be classified as simple or complex. The initial investigation of perianal fistulas includes imaging (MRI of the pelvis and rectum), examination under anaesthesia (EUA) with digital imaging, endoscopy, probing and anal ultrasound. Non-perianal fistulas require contrast imaging and/or CT/MRI for complete anatomical definition. Any abscess should be drained, and the disease extent throughout the entire gastrointestinal tract should be evaluated. Treatment goals for perianal fistulas include reduced fistula secretion or none, evaluated by clinical examination; the absence of abscesses; and patient satisfaction. MR imaging is required to demonstrate definitive fistula closure. Fistulotomy is considered for simple perianal fistulas. In complex perianal fistulas, antibiotics and azathioprine or 6-mercaptopurine, which are often combined with a loose seton, constitute the first-line medical therapy. In cases with persistent secretion, infliximab at 5 mg/kg is given at weeks 0, 2, and 6 and subsequently every 8 weeks. Adalimumab may improve fistula response in both infliximab-naive patients and following infliximab treatment failure. Local therapy with fibrin glue or fistula plugs is rarely effective. Definitive surgical closure of perianal fistulas using an advancement flap may be attempted, but this procedure is associated with a high risk of relapse. Colostomy and proctectomy are the ultimate surgical treatment options for fistulas. Intestinal resection is almost always needed for the closure of symptomatic non-perianal fistulas. PMID- 21975160 TI - Comparison of 2- and 3-dimensional shoulder ultrasound to magnetic resonance imaging in a community hospital for the detection of supraspinatus rotator cuff tears with improved worktime room efficiency. AB - PURPOSE: The purpose of this study was to evaluate whether 3-dimensional (3D) volumetric acquisition of shoulder ultrasound (US) data for supraspinatus rotator cuff tears is as sensitive when compared with conventional 2-dimensional (2D) US and routine magnetic resonance imaging (MRI), and whether there is improved workroom time efficiency when using the 3D technique compared with the 2D technique. METHODS: In this prospective study, 39 shoulders underwent US and MRI examination of their rotator cuff to confirm the accuracy of both the 2D and 3D techniques. The difference in sensitivities was compared by using confidence interval analysis. The mean times required to obtain the 2D and 3D US data and to review the scans were compared by using a 1-tailed Wilcoxon test. RESULTS: Sensitivity and specificity of 2D US in detecting supraspinatus full- and partial thickness tears was 100% and 96%, and 80% and 100%, respectively, and similar values were obtained with 3D US at 100% and 100%, and 90% and 96.6%, respectively. Analysis of the confidence limits of the sensitivities showed no significant difference. The mean time (+/- SD) of the overall 2D examination of the shoulder, including interpretation was 10.02 +/- 3.28 minutes, whereas, for the 3D examination, it was 7.08 +/- 0.35 minutes. Comparison between the 2 cohorts when using a 1-tailed Wilcoxon test showed a statistically significant difference (P < .05). CONCLUSION: 3D US of the shoulder is as accurate as 2D US when compared with MRI for the diagnosis of full- and partial-thickness supraspinatus rotator cuff tears, and 3D US examination significantly reduced the time between the initial scan and the radiologist interpretation, ultimately improving workplace efficiency. PMID- 21975162 TI - iRefScape. A Cytoscape plug-in for visualization and data mining of protein interaction data from iRefIndex. AB - BACKGROUND: The iRefIndex consolidates protein interaction data from ten databases in a rigorous manner using sequence-based hash keys. Working with consolidated interaction data comes with distinct challenges: data are redundant, overlapping, highly interconnected and may be collected and represented using different curation practices. These phenomena were quantified in our previous studies. RESULTS: The iRefScape plug-in for the Cytoscape graphical viewer addresses these challenges. We show how these factors impact on data-mining tasks and how our solutions resolve them in a simple and efficient manner. A uniform accession space is used to limit redundancy and support search expansion and searching on multiple accession types. Multiple node and edge features support data filtering and mining. Node colours and features supply information about search result provenance. Overlapping evidence is presented using a multi-graph and a bi-partite representation is used to distinguish binary and n-ary source data. Searching for interactions between sets of proteins is supported and specifically includes searches on disease-related genes found in OMIM. Finally, a synchronized adjacency-matrix view facilitates visualization of relationships between sets of user defined groups. CONCLUSIONS: The iRefScape plug-in will be of interest to advanced users of interaction data. The plug-in provides access to a consolidated data set in a uniform accession space while remaining faithful to the underlying source data. Tools are provided to facilitate a range of tasks from a simple search to knowledge discovery. The plug-in uses a number of strategies that will be of interest to other plug-in developers. PMID- 21975161 TI - Abrogation of contaminating RNA activity in HIV-1 Gag VLPs. AB - BACKGROUND: HIV-1 Gag virus like particles (VLPs) used as candidate vaccines are regarded as inert particles as they contain no replicative nucleic acid, although they do encapsidate cellular RNAs. During HIV-1 Gag VLP production in baculovirus based expression systems, VLPs incorporate the baculovirus Gp64 envelope glycoprotein, which facilitates their entry into mammalian cells. This suggests that HIV-1 Gag VLPs produced using this system facilitate uptake and subsequent expression of encapsidated RNA in mammalian cells - an unfavourable characteristic for a vaccine. METHODS: HIV-1 Gag VLPs encapsidating reporter chloramphenicol acetyl transferase (CAT) RNA, were made in insect cells using the baculovirus expression system. The presence of Gp64 on the VLPs was verified by western blotting and RT-PCR used to detect and quantitate encapsidated CAT RNA. VLP samples were heated to inactivate CAT RNA. Unheated and heated VLPs incubated with selected mammalian cell lines and cell lysates tested for the presence of CAT protein by ELISA. Mice were inoculated with heated and unheated VLPs using a DNA prime VLP boost regimen. RESULTS: HIV-1 Gag VLPs produced had significantly high levels of Gp64 (~1650 Gp64 molecules/VLP) on their surfaces. The amount of encapsidated CAT RNA/MUg Gag VLPs ranged between 0.1 to 7 ng. CAT protein was detected in 3 of the 4 mammalian cell lines incubated with VLPs. Incubation with heated VLPs resulted in BHK-21 and HeLa cell lysates showing reduced CAT protein levels compared with unheated VLPs and HEK-293 cells. Mice inoculated with a DNA prime VLP boost regimen developed Gag CD8 and CD4 T cell responses to GagCAT VLPs which also boosted a primary DNA response. Heating VLPs did not abrogate these immune responses but enhanced the Gag CD4 T cell responses by two-fold. CONCLUSIONS: Baculovirus-produced HIV-1 Gag VLPs encapsidating CAT RNA were taken up by selected mammalian cell lines. The presence of CAT protein indicates that encapsidated RNA was expressed in the mammalian cells. Heat-treatment of the VLPs altered the ability of protein to be expressed in some cell lines tested but did not affect the ability of the VLPs to stimulate an immune response when inoculated into mice. PMID- 21975163 TI - Sexual risk taking behaviour: prevalence and associated factors. A population based study of 22,000 Danish men. AB - BACKGROUND: Sexual habits and risky sexual behaviour strongly affect public health. Available data indicate that sexually transmitted infections are increasing in many EU countries. Changes in the epidemiology of sexually transmitted diseases across Europe are among other factors suggested to be driven by changes in sexual behaviour patterns. The purpose of our study is to assess the occurrence of risky behaviour in men aged 18-45 years from the general population. Furthermore, we aim to examine factors associated with risky sexual behaviour. METHODS: A random sample of 33,000 Danish men (18-45 years) was selected from the general population. The participants (participation-rate: 71.0%) received a self-administered questionnaire which could be returned in a paper-based version or as a web-based questionnaire. Non-respondents were subsequently asked to participate in a telephone interview with the same questions as in the paper- or web-based questionnaire. We defined risky sexual behaviour as > 8 lifetime sexual partners, >=2 new sexual partners in the past 6 months and intercourse with a commercial sex worker. RESULTS: The Danish men reported having had sexual intercourse with a median of 8 female partners during their lifetime and 9.8% of the men have had >=2 new sexual partners in the past 6 months. Sexual intercourse with a commercial sex worker was reported by 11.3% of the men. Furthermore, men reporting > 8 lifetime partners or >=2 recent sex partners were more likely to have other risk taking behaviours such as early sexual debut, current smoking and regular binge drinking. A similar pattern was seen in men who had sex with a commercial sex worker. CONCLUSIONS: Our results show that a high proportion of Danish men have had sexual contact with a large number of partners, and risky sexual behaviour is closely related to other risk taking behaviours such as smoking and binge drinking. PMID- 21975164 TI - Time trends and individual characteristics associated with polybrominated diphenyl ethers in breast milk samples 2006-2009 in Lower Saxony, Germany. AB - BACKGROUND: Since 2006 polybrominated diphenyl ether (PBDE) concentrations have been analyzed within the scope of the breast milk project conducted by the Governmental Institute of Public Health of Lower Saxony. OBJECTIVES: Temporal trends and regional distributions of the resident population as well as the relevance of individual factors influencing PBDE concentration were to be determined. METHODS: Four PBDE congeners (BDE-47, BDE-153, BDE-99, BDE-100) have been analyzed. The concentrations are fitted by linear regression models, whereby individual factors of the mother are surveyed by a standardized questionnaire. RESULTS: A total of 2173 samples taken between 2006 and 2009 shows an estimated total PBDE mean value of 1.68 ng/g lipid weight (l.w.). In contrast to most other studies, the proportion of BDE-153 exceeds the one of BDE-47 (median: 0.51 ng/g l.w. vs. 0.31 ng/g l.w.). BMI shows a positive correlation with BDE-47 and a negative correlation with BDE-153, both statistically significant (p<0.001). For BDE-153, other significant factors (former breast feeding periods, birth year of the mother and country of birth) reflect also dilution effects and the time of accumulation. A decreasing temporal trend is observed for BDE-47 but not for BDE 153. CONCLUSIONS: The correlation patterns, the temporal trends and the various influencing factors may reflect differences in exposure sources and/or metabolism between the major congeners BDE-47 and BDE-153. Therefore it seems to be necessary to discuss the concentrations of BDE-47 and BDE-153 separately as leading indicators instead of using a total PBDE. PMID- 21975166 TI - [Reply to the letter "Fundamental topics in the training of new diagnostic imaging specialists"]. PMID- 21975165 TI - Cytochrome P450 enzymes in the brain: emerging evidence of biological significance. AB - Cytochrome P450 (CYP) enzymes are responsible for the metabolism of many exogenous and endogenous compounds. CYPs are abundant in the liver and are also expressed in many extra-hepatic tissues including the brain. Although total CYP levels in the brain are much lower than in the liver, brain CYPs are concentrated near drug targets in specific regions and cell types, and can potentially have a considerable impact on local metabolism. Individual differences in brain CYP metabolism, due to inducers, inhibitors or genetic variation, can influence sensitivity and response to centrally acting drugs. Brain CYPs may also play a role in modulating brain activity, behavior, susceptibility to central nervous system diseases and treatment outcomes. This review highlights recent progress that has been made in understanding the functional significance of CYPs in the brain. PMID- 21975167 TI - [Technicians and ultrasound]. PMID- 21975168 TI - [Articular and periarticular tumors: differential diagnosis using magnetic resonance imaging]. AB - Most patients with articular or periarticular tumors present with chronic monoarthritis and nonspecific alterations on laboratory tests; thus, it is important to know the changes on magnetic resonance imaging (MRI) that can suggest their diagnosis and the differential diagnosis of these tumors. MRI defines the anatomic origin and the tissue characteristics of articular and periarticular tumors, making it possible to reach a specific diagnosis in most cases. It is important to evaluate the MRI findings together with the plain-film findings because this helps in the characterization of mineralized tumors. PMID- 21975169 TI - [Haemobilia secondary to a liver pseudoaneurysm after choledochostomy using a Kehr tube]. PMID- 21975171 TI - Assessment of anxiolytic and panicolytic effects of dichloromethane fraction from stems of Kielmeyera coriacea. AB - Kielmeyera coriacea Mart. (Calophyllaceae) is known popularly as "Pau Santo". The hydroethanolic extract (HE) of Kielmeyera coriacea stems and its semi-pure dichloromethane (DCM) constituent produced an antidepressant-like effect in rats. The purpose of this study was to investigate the effects of repeated administration (21 days) by gavage of the DCM fraction (5, 10 or 15mg/kg) in rats submitted to the elevated T-maze (ETM), a model of generalized anxiety and panic disorders. The tricyclic antidepressant imipramine (15mg/kg) was used as a positive control. Rat locomotion was assessed using the open field test (OFT) following each drug treatment. The 2-hydroxy-1-methoxyxanthone (1), aucuparin (2), swertinin (3), 1,3,7-trihydroxy-2-(3-methylbut-2-enyl)-xanthone (4) and 1,3,5-trihydroxy-2-(3-methylbut-2-enyl)-xanthone (5) were identified in DCM fraction, and suggest that the xanthone (4) is related with the antidepressant like profile of this plant. Pharmacological evaluation showed that DCM fraction (10 and 15 mg/kg) decreased the inhibitory avoidance latency from the closed arm and increased the one-way escape latency from the open arm in the ETM, which is indicative of anxiolytic and panicolytic effects, respectively, as occurs with the positive control, imipramine (15 mg/kg), when compared to their control group (vehicle). Locomotor activity was not significantly altered by the different treatments. This study suggests that the DCM fraction from stems of Kielmeyera coriacea can be an important therapeutic alternative in the treatment of anxiety disorders, such as generalized anxiety and panic disorders. PMID- 21975172 TI - Climate change and tropical biodiversity: a new focus. AB - Considerable efforts are focused on the consequences of climate change for tropical rainforests. However, potentially the greatest threats to tropical biodiversity (synergistic interactions between climatic changes and human land use) remain understudied. Key concerns are that aridification could increase the accessibility of previously non-arable or remote lands, elevate fire impacts and exacerbate ecological effects of habitat disturbance. The growing climatic change literature often fails to appreciate that, in coming decades, climate-land use interactions might be at least as important as abiotic changes per se for the fate of tropical biodiversity. In this review, we argue that protected area expansion along key ecological gradients, regulation of human-lit fires, strategic forest-carbon financing and re-evaluations of agricultural and biofuel subsidies could ameliorate some of these synergistic threats. PMID- 21975170 TI - Person-specific changes in motor performance accompany upper extremity functional gains after stroke. AB - In animal models, hundreds of repetitions of upper extremity (UE) task practice promote neural adaptation and functional gain. Recently, we demonstrated improved UE function following a similar intervention for people after stroke. In this secondary analysis, computerized measures of UE task performance were used to identify movement parameters that changed as function improved. Ten people with chronic poststroke hemiparesis participated in high-repetition UE task-specific training 3 times per week for 6 weeks. Before and after training, we assessed UE function with the Action Research Arm Test (ARAT), and evaluated motor performance using computerized motion capture during a reach-grasp-transport release task. Movement parameters included the duration of each movement phase, trunk excursion, peak aperture, aperture path ratio, and peak grip force. Group results showed an improvement in ARAT scores (p = .003). Although each individual changed significantly on at least one movement parameter, across the group there were no changes in any movement parameter that reached or approached significance. Changes on the ARAT were not closely related to changes in movement parameters. Since aspects of motor performance that contribute to functional change vary across individuals, an individualized approach to upper extremity motion analysis appears warranted. PMID- 21975173 TI - Increased expression of immunoreactive thymic stromal lymphopoietin in patients with severe asthma. AB - BACKGROUND: Thymic stromal lymphopoietin (TSLP) is a cytokine implicated in the pathophysiology of asthma through 2 distinct pathways: a TSLP-OX40 ligand (OX40L) T cell axis and a TSLP-mast cell axis. Whether these pathways are active in human asthma is unknown. OBJECTIVE: We sought to investigate whether mucosal TSLP protein expression relates to asthma severity and distinct immunologic pathways. METHODS: In healthy subjects and patients with mild-to-severe asthma, we immunostained bronchial biopsy specimens for TSLP, OX40, OX40L, T(H)2 cytokines, and inflammatory cell markers. We examined gene expression using RNA microarrays and quantitative RT-PCR. RESULTS: There was considerable heterogeneity in the levels of TSLP, IL-13, and IL-4 immunostaining across the cohort of asthmatic patients examined. Overall, TSLP protein expression was significantly increased in airway epithelium and lamina propria of asthmatic patients, particularly in patients with severe asthma. TSLP immunostaining in both compartments correlated with the severity of airflow obstruction. The majority of leukocytes expressing IL-13 were possibly nuocytes. Accounting for intersubject variability, the 55% of asthmatic patients with increased IL-13 immunostaining in the lamina propria also had increased IL-4 and TSLP expression. This was further substantiated by significant correlations between TSLP gene expression, a T(H)2 gene expression signature, and eosinophilic inflammation in bronchial biopsy specimens. Immunostaining for OX40, OX40L, and CD83 was sparse, with no difference between asthmatic patients and healthy subjects. CONCLUSION: TSLP expression is increased in a subset of patients with severe asthma in spite of high-dose inhaled or oral corticosteroid therapy. Targeting TSLP might only be efficacious in the subset of asthma characterized by increased TSLP expression and T(H)2 inflammation. PMID- 21975174 TI - Low incidence and high remission of allergic sensitization among adults. AB - BACKGROUND: Prospective studies on the incidence and remission of allergic sensitization among adults are rare. OBJECTIVE: We sought to assess the incidence, remission, risk factors, and prevalence of allergic sensitization in relation to aging over a 10-year period. METHODS: In 1994, a sample of 664 adults (68% of invited) participated in clinical examinations, including a structured interview and skin prick tests (SPTs). The sample was randomly selected from a large questionnaire survey in Northern Sweden. In 2004, 555 subjects (93% of invited) were re-examined by using the same methods as in 1994. IgE levels were also measured in 2004. RESULTS: In 1994, the prevalence of any positive SPT response was significantly related to age, with the highest prevalence (55%) in subjects aged 20 to 29 years and the lowest prevalence (26%) in subjects aged 50 to 60 years. A similar age-related prevalence was found in 2004, and sensitization to pollen and pets was most common in both years. The results of the SPTs were verified by means of specific IgE measurement. The incidence of any positive SPT response was low. Only 9 subjects had any positive SPT response (ie, a cumulative incidence of 5% over 10 years). Remission was greater (ie, 32% over 10 years). The main risk factors for allergic sensitization were young age and a family history of allergy. Having had furred animals at home during childhood was negatively related to specific IgE levels. CONCLUSION: The low incidence and high remission in adulthood explain the decreasing prevalence of allergic sensitization by age. Thus the low prevalence of allergic sensitization among the elderly found in cross-sectional studies is an effect of normal aging and not primarily a birth cohort effect. PMID- 21975175 TI - IL-10 controls dendritic cell-induced T-cell reactivation in the skin to limit contact hypersensitivity. AB - BACKGROUND: IL-10 is a pleiotropic cytokine and potent negative regulator of both innate and adaptive immune responses. Consequently, IL-10-deficient (IL-10(-/-)) mice have enhanced contact hypersensitivity (CHS) to topical hapten. OBJECTIVE: Although the importance of IL-10 production by (regulatory) T cells and Langerhans cells in regulating CHS has been established by cell type-specific il 10 gene targeting, it remains elusive to what extent IL-10 controls dendritic cell (DC) function in vivo. METHODS: To this aim, we generated mice with a DC specific deletion of the IL-10 receptor (IL-10R). RESULTS: Despite the ability of IL-10 to inhibit DC maturation in vitro, DCs of resting DC-IL10R(-/-) mice retained their immature phenotype in vivo. In contrast, IL-10R(-/-) DCs produced increased levels of proinflammatory cytokines and IL-10 after in vitro stimulation. Induction of CHS was indistinguishable from that seen in control mice at 24 hours after hapten challenge but resulted in increased ear swelling at 48 hours and delayed resolution of the inflammatory reaction. Adoptive T-cell transfer experiments revealed that only T-cell reactivation and not sensitization by IL-10R(-/-) DCs leads to enhanced CHS. Accordingly, the expression of proinflammatory cytokines and IL-10 was augmented in the skin of DC-IL10R(-/-) mice after hapten challenge. CONCLUSION: Our data demonstrate that IL-10 signaling in DCs is dispensable during naive T-cell priming but is critical to prevent an exaggerated effector T-cell response in the skin. PMID- 21975177 TI - Comparing the performance of two clinical models in estimating the risk of endometrial cancer in symptomatic postmenopausal women. AB - OBJECTIVE: The aim of this study was to internally evaluate the accuracy measures of the two newly developed predictive models, called DEFAB and DFAB, used to estimate the risk of endometrial cancer in postmenopausal women presenting with vaginal bleeding. STUDY DESIGN: Prospective study including postmenopausal women presenting with vaginal bleeding. RESULTS: Over a 46-month-period, 3795 postmenopausal women presented with vaginal bleeding and were included in the study. A total of 221 (6%) women were diagnosed with endometrial carcinoma. The DEFAB predictive model incorporates known risk factors such as presence of Diabetes, Endometrial thickness measurement on transvaginal ultrasonography, Frequency of bleeding, Age, and Body mass index. The DFAB model is based on the above clinical characteristics excluding the ultrasonography result. For the recommended cut-off values, there was no evidence (p-value=0.221) of a difference in the diagnostic ability with respect to sensitivity, specificity, area under receiver operating curve, positive predictive value and negative predictive value. There was strong evidence (p-value<0.0001) to suggest that the diagnostic ability of DEFAB and DFAB agree as evidenced by the excellent Kappa statistic 0.950 (95% CI 0.940-0.960). We found strong evidence (p-value<0.0001) that the variables incorporated in both predictive models simultaneously correctly classify an individual to either having cancer or not having cancer with respect to logistic discriminant analysis. CONCLUSION: We recommend that these two predictive models can be used interchangeably. PMID- 21975176 TI - Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy. AB - BACKGROUND: The main obstacle to elucidating the role of CD4(+) T cells in allergen-specific immunotherapy (SIT) has been the absence of an adequately sensitive approach to directly characterize rare allergen-specific T cells without introducing substantial phenotypic modifications by means of in vitro amplification. OBJECTIVE: We sought to monitor, in physiological conditions, the allergen-specific CD4(+) T cells generated during natural pollen exposure and during allergy vaccination. METHODS: Alder pollen allergy was used as a model for studying seasonal allergies. Allergen-specific CD4(+) T cells were tracked and characterized in 12 subjects with alder pollen allergy, 6 nonallergic subjects, and 9 allergy vaccine-treated subjects by using peptide-MHC class II tetramers. RESULTS: Allergen-specific CD4(+) T cells were detected in all of the subjects with alder pollen allergy and nonallergic subjects tested. Pathogenic responses- chemoattractant receptor homologous molecule expressed on T(H)2 lymphocytes (CRTH2) expression and T(H)2 cytokine production--are specifically associated with terminally differentiated (CD27(-)) allergen-specific CD4(+) T cells, which dominate in allergic subjects but are absent in nonallergic subjects. In contrast, CD27(+) allergen-specific CD4(+) T cells are present at low frequencies in both allergic and nonallergic subjects and reflect classical features of the protective immune response with high expression of IL-10 and IFN-gamma. Restoration of a protective response during SIT appears to be due to the preferential deletion of pathogenic (CD27(-)) allergen-specific CD4(+) T cells accompanied by IL-10 induction in surviving CD27(+) allergen-specific CD4(+) T cells. CONCLUSIONS: Differentiation stage divides allergen-specific CD4(+) T cells into 2 distinct subpopulations with unique functional properties and different fates during SIT. PMID- 21975178 TI - Congenital vesicovaginal fistula with menouria: an anomaly of the urogenital sinus. AB - OBJECTIVE: To describe the diagnostic and therapeutic process for a congenital exceptional anomaly. To analyze the pathogenesis of the embryologic anomalies associated with menouria and congenital vesicovaginal fistula (VVF). STUDY DESIGN: The case of a 28-year-old female with menouria and impossibility of consummating coitus is described. The diagnostic method is analyzed. The type of treatment is described and finally we conclude with a hypothesis about embryology of congenital anomalies with VVF and menouria. RESULTS: For management of anomalies as congenital VVF, imaging tests including cystography and urography could not correctly visualize the fistulous tract. It was identified by cystoscopy, performed during the time of menouria. Surgical treatment consisted in repairing the VVF and vaginoplasty according to the McIndoe technique. CONCLUSIONS: All women with menouria need complete investigation with exhaustive exploration, analytic evaluation, ultrasound, imaging tests (principally magnetic resonance) and, very importantly, cystoscopy on the days of menouria. Surgical treatment must be careful and individualized. This case allows us to hypothesise that the blind vagina encountered reflects an anomaly of correct urogenital sinus development. PMID- 21975179 TI - Effects of the pullover exercise on the pectoralis major and latissimus dorsi muscles as evaluated by EMG. AB - The aim of the current study was to investigate the EMG activity of pectoralis major and latissimus dorsi muscles during the pullover exercise. Eight healthy male volunteers took part in the study. The EMG activity of the pectoralis major and that of the latissimus dorsi of the right side were acquired simultaneously during the pullover exercise with a free-weight barbell during both the concentric and eccentric phases of the movement. After a warm-up, all the subjects were asked to perform the pullover exercise against an external load of 30% of their body weight, during 1 set * 10 repetitions. The criterion adopted to normalize the EMG data was the maximal voluntary isometric activation. The present findings demonstrated that the barbell pullover exercise emphasized the muscle action of the pectoralis major more than that of the latissimus dorsi, and the higher activation depended on the external force lever arm produced. PMID- 21975180 TI - Emergence of tularemia in France: paradigm of the Burgundy region. AB - We report three consecutive cases of tularemia occurring in Burgundy, France, a region previously considered not endemic for tularemia. The patients presented with varied and unspecific clinical manifestations. The epidemiological circumstances, especially the mode of contamination, were not particularly suggestive of tularemia. Serological diagnosis was delayed in two cases because of the lack of significant antibody titers at the time of admission. In contrast, a diagnosis could readily be obtained in all three cases by detection of Francisella tularensis DNA from clinical samples using PCR-based methods. These cases highlight the increased incidence and geographical spread of tularemia in France, and the usefulness of real-time PCR technology for the early diagnostic confirmation of tularemia. PMID- 21975182 TI - [Standards for patient observation are difficult to implement]. PMID- 21975181 TI - A retrospective cohort study of stroke onset: implications for characterizing short term effects from ambient air pollution. AB - BACKGROUND: Case-crossover studies used to investigate associations between an environmental exposure and an acute health response, such as stroke, will often use the day an individual presents to an emergency department (ED) or is admitted to hospital to infer when the stroke occurred. Similarly, they will use patient's place of residence to assign exposure. The validity of using these two data elements, typically extracted from administrative databases or patient charts, to define the time of stroke onset and to assign exposure are critical in this field of research as air pollutant concentrations are temporally and spatially variable. Our a priori hypotheses were that date of presentation differs from the date of stroke onset for a substantial number of patients, and that assigning exposure to ambient pollution using place of residence introduces an important source of exposure measurement error. The objective of this study was to improve our understanding on how these sources of errors influence risk estimates derived using a case-crossover study design. METHODS: We sought to collect survey data from stroke patients presenting to hospital EDs in Edmonton, Canada on the date, time, location and nature of activities at onset of stroke symptoms. The daily mean ambient concentrations of NO2 and PM(2.5) on the self-reported day of stroke onset was estimated from continuous fixed-site monitoring stations. RESULTS: Of the 336 participating patients, 241 were able to recall when their stroke started and 72.6% (95% confidence interval [CI]: 66.9-78.3%) experienced stroke onset the same day they presented to the ED. For subjects whose day of stroke onset differed from the day of presentation to the ED, this difference ranged from 1 to 12 days (mean = 1.8; median = 1). In these subjects, there were no systematic differences in assigned pollution levels for either NO2 or PM(2.5) when day of presentation rather than day of stroke onset was used. At the time of stroke onset, 89.9% (95% CI: 86.6-93.1%) reported that they were inside, while 84.5% (95% CI: 80.6 - 88.4%) reported that for most of the day they were within a 15 minute drive from home. We estimated that due to the mis-specification of the day of stroke onset, the risk of hospitalization for stroke would be understated by 15% and 20%, for NO2 and PM(2.5), respectively. CONCLUSIONS: Our data suggest that day of presentation and residential location data obtained from administrative records reasonably captures the time and location of stroke onset for most patients. Under these conditions, any associated errors are unlikely to be an important source of bias when estimating air pollution risks in this population. PMID- 21975183 TI - [The complexity of the implementation of an observation and tracking chart for critical illness]. AB - Critically ill patients on wards are identified too late. At Aarhus University Hospital, Aarhus Sygehus, staff did not act appropriate to unacceptable values. The solution presented is development and implementation of a Track and Trigger System: a standardised observation chart encompassing frequency of vital signs measurement combined with a decision algorithm based on scores dictating skill level of decision-making. Educational programmes and specialist function for ward staff as well as action cards containing identification, situation, background, analysis, and advice and an airway, breathing, circulation, disability and environment approach to support clinical decision-making are introduced. PMID- 21975184 TI - [Triage quickens the treatment of the most sick patients]. AB - Systematic process triage is a relatively unknown concept in Denmark. Currently there are no national recommendations regarding triage models for use in the emergency department (ED). Four medium-sized EDs from different regions across the country cooperated in a joint venture to develop a new triage model, Danish Emergency Process Triage (DEPT). DEPT is inspired by the Swedish ADAPT system, but modified for a Danish context. This paper summarizes the cumulated experience with the new system. PMID- 21975185 TI - [People's cancer awareness and beliefs]. AB - Lack of awareness of cancer symptoms, cancer risk factors, and erroneous beliefs about cancer may influence delay in presentation of cancer symptoms and thereby treatment outcomes. This paper refers cancer awareness population studies (mainly from the UK) and describes associations between elements of the Health Belief Model and cancer-related health behavior. Denmark is part of the International Cancer Benchmarking Partnership which, inter alia, will examine whether differences in cancer survival across countries can be explained by different levels of cancer awareness and erroneous beliefs about cancer. PMID- 21975186 TI - [An oto-neurological approach to the acutely dizzy patient]. AB - Benign paroxysmal positional vertigo, vestibular neuronitis and Meniere's disease cause most cases of acute vertigo. However, doctors must consider central neurological reasons to vertigo. If it is determined that a patient has oto neurological vertigo, the next task is to determine whether the patient has a peripheral or a central cause of vertigo, if the condition is potentially lethal and if there is a need for acute radiological imaging and/or medical intervention. This review highlights the oto-neurological approach to the dizzy patient with particular focus on the patient's history, clinical tests and treatment. PMID- 21975187 TI - [Cogan's syndrome--an interdisciplinary diagnostic challenge]. AB - Cogan's syndrome is a rare autoimmune-like disorder characterised by nonsyphilitic interstitial keratitis and Meniere's syndrome-like audiovestibular function disorder. David G. Cogan initially described the syndrome in 1945. In 1980 Haynes et al proposed diagnostic criteria for patients with other ocular symptoms and suggested this to be atypical Cogan's syndrome. We report a case of a 43 year-old woman with atypical Cogan's syndrome. The patient received a cochlear implant prior to diagnosis. PMID- 21975188 TI - [Sandfly virus meningitis in a Danish traveller returning from Tuscany]. AB - We report the first case of Sandfly virus meningitis in a Danish traveller returning from Tuscany. A 52 year-old man was admitted with headache, fever and photophobia. Spinal fluid showed evidence of aseptic meningitis. Indirect immuno fluorescence assays showed presence of immunoglobulin (Ig)M and IgG antibodies reactive against Toscana virus, and Phlebovirus RNA was detected in blood by real time polymerase chain reaction. The patient recovered spontaneously. Since Sandfly virus is a very common cause of meningitis in the Mediterranean countries, it is important to be aware of this disease in travellers returning from these areas. PMID- 21975189 TI - Short-term exposure to an endocrine disruptor affects behavioural consistency in male threespine stickleback. AB - It has been established that exposure to xenooestrogens can have profound effects on reproductive and aggressive behaviours in aquatic organisms. Studies on the effects of 17alpha-ethinyloestradiol (EE2) on behaviour, however, rarely examine these effects over multiple trials, across time, or across contexts. In addition, it is possible that individuals vary in their sensitivity to EE2 and individuals may differ in the degree to which their behaviour is affected. The study of consistent individual differences in behaviour has grown in popularity in recent years perhaps because of the evolutionary questions this behavioural variation raises. Adult male threespine stickleback (Gasterosteus aculeatus) from an anadromous population repeatedly received the simultaneous presentation of a dummy male and dummy female conspecific both before and after exposure to a short term, nominal (15 ng L(-1)) concentration of 17alpha-ethinyloestradiol (EE2). These before and after measures were then compared against one another as well as against responses of males in a control group that was not exposed to EE2. Courtship, aggression, and nesting behaviours were all affected by EE2 exposure. In addition, behavioural consistency over trials was markedly reduced after EE2 exposure, as shown by lower repeatability values in the after exposure measures and in weaker correlations between the before and after exposure measures in the EE2 group compared to the control group. This suggests that male threespine stickleback vary in their sensitivity to EE2. This study is one of the first to examine the effects of short-term EE2 exposure on behaviour across trials and has important implications for population-level fitness consequences of xenooestrogens. PMID- 21975190 TI - Protrusio acetabuli and total hip arthroplasty in patients with Marfan syndrome. AB - Our goals were (1) to quantify protrusio acetabuli in patients with Marfan syndrome who underwent total hip arthroplasty and (2) to identify clinical results and complications associated with total hip arthroplasty in those patients. We reviewed the preoperative radiographs of the 29 patients (38 hips) in our study and analyzed the related patient operative reports, postoperative records, and self-administered questionnaires (mean follow-up, 116 +/- 102 months). The mean preoperative center-edge angle of Wiberg was 50.9 degrees +/- 14 degrees . Loosening (3) and radiolucent lines (4) occurred in femoral but not acetabular components. The hips had 15 complications, including 8 reoperations. High questionnaire scores (82 +/- 13 points) indicated good hip function regardless of preoperative protrusio severity. PMID- 21975191 TI - Evolution of the apomixis transmitting chromosome in Pennisetum. AB - BACKGROUND: Apomixis is an intriguing trait in plants that results in maternal clones through seed reproduction. Apomixis is an elusive, but potentially revolutionary, trait for plant breeding and hybrid seed production. Recent studies arguing that apomicts are not evolutionary dead ends have generated further interest in the evolution of asexual flowering plants. RESULTS: In the present study, we investigate karyotypic variation in a single chromosome responsible for transmitting apomixis, the Apospory-Specific Genomic Region carrier chromosome, in relation to species phylogeny in the genera Pennisetum and Cenchrus. A 1 kb region from the 3' end of the ndhF gene and a 900 bp region from trnL-F were sequenced from 12 apomictic and eight sexual species in the genus Pennisetum and allied genus Cenchrus. An 800 bp region from the Apospory-Specific Genomic Region also was sequenced from the 12 apomicts. Molecular cytological analysis was conducted in sixteen Pennisetum and two Cenchrus species. Our results indicate that the Apospory-Specific Genomic Region is shared by all apomictic species while it is absent from all sexual species or cytotypes. Contrary to our previous observations in Pennisetum squamulatum and Cenchrus ciliaris, retrotransposon sequences of the Opie-2-like family were not closely associated with the Apospory-Specific Genomic Region in all apomictic species, suggesting that they may have been accumulated after the Apospory-Specific Genomic Region originated. CONCLUSIONS: Given that phylogenetic analysis merged Cenchrus and newly investigated Pennisetum species into a single clade containing a terminal cluster of Cenchrus apomicts, the presumed monophyletic origin of Cenchrus is supported. The Apospory-Specific Genomic Region likely preceded speciation in Cenchrus and its lateral transfer through hybridization and subsequent chromosome repatterning may have contributed to further speciation in the two genera. PMID- 21975192 TI - An exploration of economic reasoning in hoarding disorder patients. AB - Current models of hoarding disorder (HD) emphasize problems of decision-making. Evidence for neuropsychological impairment in HD, however, has been mixed. The present study examined whether HD patients show problems of economic reasoning that could be associated with decision-making problems. Forty-two HD patients, 29 obsessive-compulsive disorder (OCD) patients, and 36 healthy control participants completed the Iowa gambling task (IGT), a computerized card playing game that assesses participants' ability to learn and utilize a rule of sacrificing short term gain for long-term gain, and a cognitive dissonance reduction task that measured changes in preference for items (art prints) after selecting or rejecting them. Results showed no deficits on the IGT for HD participants, and no difference in dissonance reduction results after selecting or rejecting items on the dissonance reduction task. Furthermore, performance on these two tasks was unrelated to hoarding symptom severity or self-reported indecisiveness. It is suggested that the problems of cognitive processing in HD patients may be largely related to as-yet understudied processes, including idiosyncratic categorization problems for personally-owned items as well as other aspects of economic reasoning. PMID- 21975193 TI - A feasibility study of Acceptance and Commitment Therapy for emotional dysfunction following psychosis. AB - The experience of psychosis can lead to depression, anxiety and fear. Acceptance and Commitment Therapy (ACT) facilitates individuals to accept difficult mental experiences and behave in ways that are consistent with personally held values. This study was a single (rater) blind pilot randomised controlled trial of ACT for emotional dysfunction following psychosis. Twenty-seven participants with psychosis were randomised to either: ten sessions of ACT plus treatment as usual (TAU) or TAU alone. The Hospital Anxiety and Depression Scale, Positive and Negative Syndrome Scale, Acceptance and Action Questionnaire, Kentucky Inventory of Mindfulness Skills and Working Alliance Inventory were used. Individuals were assessed at baseline and 3 months post-baseline. The individuals randomised to receive ACT found the intervention acceptable. A significantly greater proportion of the ACT group changed from being depressed at time of entry into the study to not being depressed at follow-up. The ACT group showed a significantly greater increase in mindfulness skills and reduction in negative symptoms. Results indicated that individuals randomised to ACT had significantly fewer crisis contacts over the study. Changes in mindfulness skills correlated positively with changes in depression. ACT appears to offer promise in reducing negative symptoms, depression and crisis contacts in psychosis. PMID- 21975194 TI - A translational behavioral model of mood-based impulsivity: Implications for substance abuse. AB - BACKGROUND: Laboratory tasks that measure various facets of impulsivity derived from self-report questionnaires are important for elucidating the behavioral consequences of impulsivity in humans and for back-translating these facets to non-human species. Negative urgency, or mood-based rash action, is a self-report facet of impulsivity linked to problem substance use; however, a valid behavioral task is lacking. METHODS: The current studies were designed to bridge self-report questionnaire and behavioral measures of negative urgency in humans and to determine if this could be back-translated to rats. RESULTS: Humans scoring high in negative urgency showed greater behavioral responding and increased frustration following unexpected reward omission on a monetary-based task compared to subjects low in negative urgency. Rats also showed elevated responding for either sucrose pellets or intravenous amphetamine following unexpected reward omission. CONCLUSION: These results suggest that impulsive behavior engendered by unexpected reward omission may represent a valid behavioral model of negative urgency linked to substance abuse. PMID- 21975195 TI - Separate and combined effects of the GABA reuptake inhibitor tiagabine and Delta9 THC in humans discriminating Delta9-THC. AB - BACKGROUND: The involvement of non-cannabinoid neurotransmitter systems in the abuse-related behavioral effects of cannabis has not been well characterized in humans. GABAergic drugs have overlapping effects with cannabis and Delta(9) tetrahydrocannabinol (Delta(9)-THC) on certain behavioral measures, but those measures lack the specificity to draw conclusions regarding the involvement of GABA in cannabinoid effects. The aim of this study was to assess the separate and combined effects of the GABA reuptake inhibitor tiagabine and Delta(9)-THC using more pharmacologically specific drug-discrimination procedures. METHODS: Eight cannabis users learned to discriminate 30 mg oral Delta(9)-THC from placebo and then received tiagabine (6 and 12 mg), Delta(9)-THC (5, 15 and 30 mg) and placebo, alone and in combination. Self-report, task performance and physiological measures were also collected. RESULTS: Delta(9)-THC produced subjective effects typically associated with cannabinoids (e.g., High, Stoned, Like Drug), elevated heart rate and impaired rate and accuracy on psychomotor performance tasks. The higher tiagabine dose substituted for the Delta(9)-THC discriminative stimulus and engendered subjective and performance-impairing effects that overlapped with those of Delta(9)-THC when administered alone. In combination, tiagabine shifted the discriminative-stimulus effects of Delta(9) THC leftward/upward and enhanced Delta(9)-THC effects on other outcomes. CONCLUSIONS: These results indicate that GABA is involved in the clinical effects of Delta(9)-THC, and by extension, cannabis. Future studies should test selective GABAergic compounds to determine which receptor subtype(s) are responsible for the effects observed when combined with cannabinoids. PMID- 21975196 TI - Skeletal muscle protein metabolism in the elderly: Interventions to counteract the 'anabolic resistance' of ageing. AB - Age-related muscle wasting (sarcopenia) is accompanied by a loss of strength which can compromise the functional abilities of the elderly. Muscle proteins are in a dynamic equilibrium between their respective rates of synthesis and breakdown. It has been suggested that age-related sarcopenia is due to: i) elevated basal-fasted rates of muscle protein breakdown, ii) a reduction in basal muscle protein synthesis (MPS), or iii) a combination of the two factors. However, basal rates of muscle protein synthesis and breakdown are unchanged with advancing healthy age. Instead, it appears that the muscles of the elderly are resistant to normally robust anabolic stimuli such as amino acids and resistance exercise. Ageing muscle is less sensitive to lower doses of amino acids than the young and may require higher quantities of protein to acutely stimulate equivalent muscle protein synthesis above rest and accrue muscle proteins. With regard to dietary protein recommendations, emerging evidence suggests that the elderly may need to distribute protein intake evenly throughout the day, so as to promote an optimal per meal stimulation of MPS. The branched-chain amino acid leucine is thought to play a central role in mediating mRNA translation for MPS, and the elderly should ensure sufficient leucine is provided with dietary protein intake. With regards to physical activity, lower, than previously realized, intensity high-volume resistance exercise can stimulate a robust muscle protein synthetic response similar to traditional high-intensity low volume training, which may be beneficial for older adults. Resistance exercise combined with amino acid ingestion elicits the greatest anabolic response and may assist elderly in producing a 'youthful' muscle protein synthetic response provided sufficient protein is ingested following exercise. PMID- 21975197 TI - Transcobalamin 2 variant associated with poststroke homocysteine modifies recurrent stroke risk. AB - OBJECTIVES: The Vitamin Intervention for Stroke Prevention trial found an association between baseline poststroke homocysteine (Hcy) and recurrent stroke. We investigated genes for enzymes and cofactors in the Hcy metabolic pathway for association with Hcy and determined whether associated single nucleotide polymorphisms (SNPs) influenced recurrent stroke risk. METHODS: Eighty-six SNPs in 9 candidate genes (BHMT1, BHMT2, CBS, CTH, MTHFR, MTR, MTRR, TCN1, and TCN2) were genotyped in 2,206 subjects (83% European American). Associations with Hcy measures were assessed using linear regression models assuming an additive genetic model, adjusting for age, sex, and race and additionally for baseline Hcy when postmethionine load change was assessed. Associations with recurrent stroke were evaluated using survival analyses. RESULTS: Five SNPs in the transcobalamin 2 (TCN2) gene were associated with baseline Hcy (false discovery rate [FDR] adjusted p = 0.049). TCN2 SNP rs731991 was associated with recurrent stroke risk in the low-dose arm of the trial under a recessive model (log-rank test p = 0.009, hazard ratio 0.34). Associations with change in postmethionine load Hcy levels were found with 5 SNPs in the cystathionine beta-synthase (CBS) gene (FDR adjusted p < 0.031). CONCLUSIONS: TCN2 variants contribute to poststroke Hcy levels, whereas variants in the CBS gene influence Hcy metabolism. Variation in the TCN2 gene also affects recurrent stroke risk in response to cofactor therapy. PMID- 21975198 TI - Meralgia paresthetica: relation to obesity, advanced age, and diabetes mellitus. AB - OBJECTIVE: To determine the incidence of meralgia paresthetica (MP) and its relationship to diabetes mellitus (DM) and obesity. METHODS: A population-based study was performed within Olmstead County Minnesota, from January 1, 1990, to December 31, 1999. MP incidence and its association with age, gender, body mass index (BMI), and DM were reviewed. RESULTS: A total of 262 patients with MP, 262 normal controls, and 262 BMI-matched normal controls with mean age of 50 years were identified (51% men). The age- and sex-adjusted incidence of MP was 32.6 per 100,000 patient years, whereas the incidence of MP in people with DM was 247 per 100,000 patient years, 7 times the occurrence of MP in the general population. Of the patients with MP, 28% had DM vs 17% of BMI-matched controls and the majority of people with MP developed DM after the diagnosis of MP. Patients with MP are 2 times more likely to develop DM (odds ratio 2, 95% confidence interval 1.3-3.0, p = 0.0027). The mean BMI of patients with MP (30.1 kg/m(2), obese class I) was significantly higher than that of age- and gender-matched controls (27.3 kg/m(2), overweight). MP incidence increased 12.9 per 100,000 patient years in the hemidecade study period with an associated increase in both BMI (2.2 kg/m(2)) and average age (3 years). CONCLUSIONS: MP is a frequent painful neuropathy associated with obesity, advancing age, and DM. The incidence rate of MP is predicted to increase as these demographics increase in world populations. Because MP associates with DM beyond weight- and age-matched controls, more aggressive counseling of these patients in prevention of DM may be warranted. PMID- 21975199 TI - The long march to surrogates of meaningful clinical outcomes in MS trials: are we there yet? PMID- 21975200 TI - Combined MRI lesions and relapses as a surrogate for disability in multiple sclerosis. AB - OBJECTIVE: In multiple sclerosis (MS), the aim of therapies is to prevent the accumulation of irreversible disability. This is difficult to assess given the short time course of clinical trials. MRI markers and relapses are often used as surrogate of disability in MS studies, but their validity remains controversial. We sought to validate, at the individual patient level, MRI lesions and relapses as surrogates for disability progression over the course of MS trials. METHODS: Individual patient data from a large, placebo-controlled trial of interferon beta 1a in relapsing-remitting MS (RRMS) were analyzed. The Prentice criteria were applied to evaluate surrogacy of 1-year MRI active lesions and relapses for disability worsening (Expanded Disability Status Scale [EDSS]) over the 2-year follow-up. RESULTS: All Prentice criteria were satisfied. Treatment reduced by 31% the odds of having EDSS worsening over 2 years, reducing the mean number of MRI lesions by 61% and the mean number of relapses by 36% over 1 year. Both 1 year MRI lesion activity and relapses, when considered independently, accounted for more than 60% of the treatment effect on 2-year EDSS worsening. A combination of 1-year MRI lesion activity and relapses explained 100% of the treatment effect on EDSS worsening over 2 years. CONCLUSIONS: A combined measure of 1-year changes in MRI lesions and relapses after interferon therapy fully estimated the corresponding effect on 2-year EDSS worsening. This short-term combined measure appears to be a surrogate for disability progression over a longer term when evaluating the effect of interferon in RRMS. PMID- 21975201 TI - MR brain iron mapping in MS: a potential neurodegenerative marker or just another technique? PMID- 21975203 TI - Early seizures in intracerebral hemorrhage: incidence, associated factors, and outcome. AB - OBJECTIVE: In patients with spontaneous intracerebral hemorrhage (ICH), the occurrence of early seizures (ES) may be a prognostic marker. Therefore, we aimed to identify incidence, associated factors, and influence on outcome of ES in patients with ICH. METHODS: Between November 2004 and March 2009, we prospectively recruited 562 consecutive adults with a spontaneous ICH (Prognosis of InTra-Cerebral Hemorrhage cohort). Patients with previous seizures (n = 40) were excluded. ES were defined as seizures occurring within 7 days of stroke onset, and their associated factors were identified with Cox regression. For a subgroup of onset seizures, we used logistic regression. Data influencing outcome (mortality at day 7 and month 6 and functional outcome at month 6) were studied using survival analyses. RESULTS: ES occurred in 71 (14%; 95% confidence interval [CI] 11-17) of 522 patients (274 male; median age 72 years, interquartile range 58-79 years). The only factor associated with ES was cortical involvement of ICH (odds ratio [OR] = 2.06; 95% CI 1.28-3.31). Regarding onset seizures (n = 38) (7%; 95% CI 5-10), associated factors were previous ICH (OR = 4.76; 95% CI 1.53 14.84), cortical involvement (OR = 2.21; 95% CI 1.11-4.43), younger age (OR = 0.97 per 1 year increase; 95% CI 0.95-0.99), and severity of the neurologic deficit at admission (OR = 1.03 per 1 point increase in the National Institutes of Health Stroke Scale score; 95% CI 1.01-1.06). ES did not influence vital or functional outcome. CONCLUSIONS: ES are a frequent complication in patients with spontaneous ICH; however, their occurrence does not influence outcome at 6 months. PMID- 21975204 TI - Reversible right vagal neuropathy. PMID- 21975202 TI - Age-related changes in the default mode network are more advanced in Alzheimer disease. AB - OBJECTIVE: To investigate age-related default mode network (DMN) connectivity in a large cognitively normal elderly cohort and in patients with Alzheimer disease (AD) compared with age-, gender-, and education-matched controls. METHODS: We analyzed task-free-fMRI data with both independent component analysis and seed based analysis to identify anterior and posterior DMNs. We investigated age related changes in connectivity in a sample of 341 cognitively normal subjects. We then compared 28 patients with AD with 56 cognitively normal noncarriers of the APOE epsilon4 allele matched for age, education, and gender. RESULTS: The anterior DMN shows age-associated increases and decreases in fontal lobe connectivity, whereas the posterior DMN shows mainly age-associated declines in connectivity throughout. Relative to matched cognitively normal controls, subjects with AD display an accelerated pattern of the age-associated changes described above, except that the declines in frontal lobe connectivity did not reach statistical significance. These changes survive atrophy correction and are correlated with cognitive performance. CONCLUSIONS: The results of this study indicate that the DMN abnormalities observed in patients with AD represent an accelerated aging pattern of connectivity compared with matched controls. PMID- 21975205 TI - Hypereosinophilia in patients with multiple sclerosis treated with natalizumab. AB - OBJECTIVE: To report asymptomatic hypereosinophilia as a potential side effect in patients treated with natalizumab, an alpha-4 integrin blocking agent. METHODS: A case series of 3 patients treated with natalizumab for relapsing-remitting multiple sclerosis including functional and phenotypic characterization of their peripheral blood lymphocytes and eosinophils is presented. RESULTS: Marked peripheral blood eosinophilia with more than 2,000 cells/mm(3) emerged in all 3 patients after the fourth natalizumab infusion and was asymptomatic. Hypereosinophilia was associated with enhanced Th2 activity, ceased with drug discontinuation, and in 2 of 3 patients recurred with drug resumption. Despite persistently high eosinophil counts, there were no signs of end-organ damage. CONCLUSIONS: Hypereosinophilia may occur during treatment with natalizumab. It seems to reflect enhanced Th2 activity and recedes with systemic corticosteroids. If the patient is asymptomatic, natalizumab may be continued, provided that other causes of eosinophilia are excluded and the patient is carefully monitored. PMID- 21975207 TI - Effect of public deliberation on attitudes toward surrogate consent for dementia research. AB - OBJECTIVE: To assess the informed, deliberative views of the older general public toward a policy of allowing surrogate consent for Alzheimer disease (AD) research. METHODS: A total of 503 persons aged 50+ recruited by random digit dialing were randomly assigned to 1 of 3 groups: deliberation, education, or control. The deliberation group attended an all-day education/peer deliberation session; the education group received written information only. Participants were surveyed at baseline, after deliberation session (or equivalent time), and 1 month after the session, regarding their attitudes toward a policy of allowing surrogate consent for research studies of varying risks and potential benefits (a lumbar puncture study, a drug randomized controlled trial, a vaccine randomized controlled trial, and an early phase gene transfer trial). RESULTS: At baseline, a policy of surrogate consent for AD research was supported by 55%-91%, depending on the scenario. The education group had a transient increase in support for one research scenario after receiving the information materials. In the deliberation group, support for surrogate consent was higher after deliberation for all scenarios (67% to 97%), with much of the increase sustained 1 month after the deliberation session. No changes occurred in the control group. The study's limitations include self-selection of participants due to the demanding nature of attendance at the deliberation sessions. CONCLUSIONS: This sample of the older general public generally supported a policy of surrogate consent for AD research at baseline. Their support increased with democratic deliberation involving informed, in-depth exploration of the relevant scientific and ethical issues. PMID- 21975209 TI - Self-rated health and risk of incident dementia: a community-based elderly cohort, the 3C study. AB - OBJECTIVES: We examined the relationship between self-rated health and incident dementia, and investigated the impact of cognitive complaints, depressive symptoms, and functional status on this relationship. METHODS: Participants of the 3C Study, a prospective cohort study composed of 8,169 community-dwelling persons aged >=65 years, were asked to rate their health at the baseline examination in 1999-2001. They were followed for a median of 6.7 years during which dementia was screened and diagnosed. Hazard ratios (HR) of dementia according to baseline self-rated health (good, fair, or poor) were estimated with a Cox model adjusted for potential confounders. RESULTS: During the 46,990 person years of follow-up, 618 participants developed dementia. Risk of dementia was increased in participants with poor (adjusted HR 1.70, 95% confidence interval [CI] 1.22-2.37) or fair (adjusted HR 1.34, 95% CI 1.13-1.59) self-rated health compared to those with good self-rated health. Poor self-rated health was associated with both AD (1.48, 1.00-2.24) and vascular dementia (3.38, 1.25 9.17). Self-rated health was a stronger predictor of dementia in participants without cognitive complaints (risk of dementia in subjects without cognitive complaints rating their health as poor: 1.96 [1.24-3.09], p = 0.004) and in those without functional disability. CONCLUSIONS: Participants rating their health as poor or fair at baseline were at increased risk of incident dementia during follow-up. Self-rated health could help raise awareness of medical doctors about a patient's risk of dementia, especially in those without conditions indicative of potential cognitive impairment. PMID- 21975210 TI - Determinants of brain iron in multiple sclerosis: a quantitative 3T MRI study. AB - OBJECTIVES: Abnormal high cerebral iron deposition may be implicated in chronic neurologic disorders, including multiple sclerosis (MS). R2* relaxometry has been recently validated in a postmortem study to indicate brain iron accumulation in a quantitative manner. We used this technique to assess brain iron levels in different stages of MS and healthy controls (HC) and determined their relation with demographic, clinical, neuropsychological, and other imaging variables. METHODS: We studied 113 consecutive patients (35 clinically isolated syndrome [CIS], 78 MS) and 35 HC with 3 T MRI and clinical and neuropsychological examination. Iron deposition in subcortical gray matter structures was assessed by automated, regional calculation of R2* rates. RESULTS: Basal ganglia (BG) R2* levels were significantly increased in MS compared to CIS (p < 0.001) and HC (p < 0.005). They were correlated with age (r = 0.5, p < 0.001), disease duration (r = 0.5, p < 0.001), Expanded Disability Status Scale (r = 0.3, p < 0.005), and the z values of mental processing speed (r = -0.3, p < 0.01). Stepwise linear regression analysis revealed gray matter atrophy as the strongest independent predictor of BG R2* levels (p < 0.001), followed by age (p < 0.001) and T2 lesion load (p < 0.005). CONCLUSION: BG iron accumulation in MS occurs with advancing disease and is related to the extent of morphologic brain damage, which argues for iron deposition as an epiphenomenon. The absence of increased iron levels in patients with CIS indicates that iron accumulation does not precede the development of MS. PMID- 21975211 TI - Editor's note: self-rated health and risk of incident dementia: a community- based elderly cohort, the 3C study. PMID- 21975208 TI - Incidence and predictors of acute symptomatic seizures after stroke. AB - OBJECTIVE: To assess incidence and predictors of acute symptomatic seizures in a prospective cohort of patients with first stroke. METHODS: Patients with first stroke hospitalized in 31 Italian centers were recruited. Relevant demographic data, disease characteristics, and risk factors were collected. Acute symptomatic seizures (<=7 days) were recorded and correlated to age, gender, family history of epilepsy, and vascular risk factors. RESULTS: A total of 714 patients (315 women, 399 men; age 27-97 years) were enrolled. A total of 609 (85.3%) had cerebral infarction (32 cerebral infarction with hemorrhagic transformation [CIHT]) and 105 (14.7%) primary intracerebral hemorrhage (PIH). A total of 141 (19.7%) had a large lesion (>3 cm) and 296 (41.5%) cortical involvement. Twelve patients reported family history of seizures. Forty-five patients (6.3%) presented acute symptomatic seizures, 24 with cerebral infarction (4.2%), 4 with CIHT (12.5%), and 17 (16.2%) with PIH. In multivariate analysis, compared to cerebral infarction, PIH carried the highest risk (odds ratio [OR] 7.2; 95% confidence interval [CI] 3.5-14.9) followed by CIHT (OR 2.7; 95% CI 0.8-9.6). Cortical involvement was a risk factor for PIH (OR 6.0; 95% CI 1.8-20.8) and for CI (OR 3.1; 95% CI 1.3-7.8). Hyperlipidemia (OR 0.2; 95% CI 0.03-0.8) was a protective factor for IPH. CONCLUSION: The incidence of acute symptomatic seizures is the highest reported in patients with first stroke with prospective follow-up. Hemorrhagic stroke and cortical lesion were independent predictors of acute symptomatic seizures. Hyperlipidemia was a protective factor for hemorrhagic stroke. PMID- 21975212 TI - Vertebral artery dissection leading to stroke caused by violent neck tics of Tourette syndrome. PMID- 21975213 TI - A ticcing time bomb? PMID- 21975206 TI - A phase III study evaluating the efficacy and safety of MBP8298 in secondary progressive MS. AB - OBJECTIVE: To evaluate the efficacy and safety of MBP8298 in subjects with secondary progressive multiple sclerosis (SPMS) who express human leukocyte antigen (HLA) haplotype DR2 or DR4 (DR2(+) or DR4(+)). METHODS: This multicenter randomized 2-year, double-blind, placebo-controlled study included 612 subjects with a diagnosis of SPMS and an Expanded Disability Status Scale (EDSS) score of 3.5-6.5, stratified according to baseline EDSS score (3.5-5.0, or 5.5-6.5) and HLA haplotype (DR2(+) or DR4(+), or DR2(-)/DR4(-)). Upon entry of 100 DR2(-)/DR4( ) subjects, further study enrollment was limited to DR2(+) or DR4(+) subjects. Subjects were randomly assigned to either 500 mg MBP8298 or placebo, given by IV injection once every 6 months for 2 years. The primary outcome measure was time to progression by >=1.0 EDSS point (or 0.5 point if baseline EDSS was 5.5 or higher), confirmed 6 months later. Secondary outcomes included mean change in EDSS, mean change in Multiple Sclerosis Functional Composite, MRI changes, annualized relapse rate, and quality of life. RESULTS: There were no significant differences between treatment groups in either the primary or secondary endpoints. MBP8298 was well tolerated in all treated subjects with no safety issues identified. CONCLUSION: In the population studied, treatment with MBP8298 did not provide a clinical benefit compared to placebo. CLASSIFICATION OF EVIDENCE: This study provides Class 1 evidence that MBP8298 is not effective in patients with SPMS who are HLA DR2(+) or DR4(+). PMID- 21975214 TI - Mental ill-health across the continuum of body mass index. AB - BACKGROUND: Several studies have found a non-linear relationship between mental ill-health and BMI with higher rates in both the underweight and the obese. This study evaluated the shape of the relationship between BMI and distress, suicidal ideation and self-reported mental ill-health conditions in a large population sample. METHODS: Data were drawn from the South Australian Monitoring and Surveillance System (SAMSS) for the years 2002 to 2009 (n = 46,704). SAMSS monitors population trends in state and national risk factors and chronic diseases. Samples are drawn from all households with a functioning number in the Australian White Pages. Computer assisted telephone interviews collected information on self-reported height and weight, demographic and health behaviours. Respondents completed the Kessler Distress and suicidal ideation scales and reported specific mental ill-health conditions. BMI was categorized into deciles to allow for assessment of the shape of any associations with other variables. Logistic regression was used to examine associations between each mental ill-health condition and BMI-decile controlling for age in the base model. This was followed by a full model that added SES and the health-adverse coping behaviours of smoking, alcohol and physical activity to test for changes from the base model. RESULTS: Non-linear associations were observed between BMI-decile and mental ill-health but statistically significantly greater odds of mental ill health were observed only in the obese and not in the underweight after controlling for age, health-adverse behaviours and socioeconomic status. The association between BMI and mental ill-health might best be described as 'threshold'. Elevated odds were apparent for middle-aged persons, whereas younger and older individuals had a significantly lower odds of having a mental ill health condition. CONCLUSIONS: In conclusion, this study has provided no support for the hypothesis of increased mental ill-health problems in the underweight but it has demonstrated the non-linear relationships between BMI and mental ill health and between BMI and health-adverse behaviours. Non-linear relationships with BMI need to be recognized and addressed during analysis. PMID- 21975215 TI - Factors associated with antimicrobial-resistant Escherichia coli in zoo animals. AB - Factors associated with the carriage of antimicrobial-resistant Escherichia coli isolates were analysed among zoo animals. An association was observed between selection of amoxicillin as the first-line therapy and a significantly higher percentage of resistance to ampicillin (54.5%) from 11 animals treated with antimicrobials, compared with isolates from 32 untreated animals (9.4%). In addition, the percentage resistance to kanamycin (36.4%), gentamicin (27.3%), trimethoprim (27.3%) and tetracycline (63.6%) from 11 treated animals was significantly higher than those from 32 untreated animals (3.1%, 3.1%, 3.1% and 25%, respectively), although these antimicrobials were rarely used. All kanamycin , gentamicin- and trimethoprim-resistant isolates and more than half of the tetracycline-resistant isolates from treated animals were also resistant to ampicillin. Co-resistance to other antimicrobials with ampicillin was suggested to contribute to an increasing of resistance towards antimicrobials that were rarely administered. The present investigation revealed an association of antimicrobial treatment with the spread of antimicrobial-resistant bacteria among zoo animals. PMID- 21975219 TI - Effect of biofilm formation on the survival of Acinetobacter baumannii on dry surfaces. AB - BACKGROUND: Acinetobacter baumannii is emerging as an important hospital pathogen, which can persist in the environment for extended periods of time. It is known to produce biofilms, a community of bacteria enclosed within a protective polymeric matrix. AIM: To establish whether the effect of biofilm formation by Acinetobacter baumannii may be associated with persistence in the hospital environment. METHODS: The effect of biofilm formation on the survival of A. baumannii on dry surfaces was investigated in biofilm-forming compared to non biofilm-forming strains. Survival assays were determined by viable counts of the cells inoculated on to glass cover slips and stored under controlled conditions of temperature and relative humidity. FINDINGS: The survival times for the biofilm-forming strains were longer than for the non-biofilm-forming ones (36 vs 15 days, respectively, P<0.001). Scanning and transmission electron microscopy studies showed a polysaccharide layer and appendages in the biofilm-forming strains, not in the non-biofilm forming ones. CONCLUSION: Biofilm formation increases the survival rate of A. baumannii on dry surfaces and may contribute to its persistence in the hospital environment, increasing the probability of causing nosocomial infections and outbreaks. PMID- 21975218 TI - E4BP4 facilitates glucocorticoid-evoked apoptosis of human leukemic CEM cells via upregulation of Bim. AB - BACKGROUND: Synthetic GCs serve as therapeutic agents for some lymphoid leukemias because of their ability to induce transcriptional changes via the GC receptor (GR) and trigger apoptosis. Upregulation of the BH3-only member of Bcl-2 family proteins, Bim, has been shown to be essential for GC-evoked apoptosis of leukemic lymphoblasts. Using human T cell leukemic sister clones CEM-C7-14 and CEM-C1-15, we have previously shown that the bZIP transcriptional repressor, E4BP4, is preferentially upregulated by GCs in CEM-C7-14 cells that are susceptible to GC evoked apoptosis, but not in refractory CEM-C1-15 cells. E4BP4 is an evolutionarily conserved member of the PAR family of bZIP transcription factors related to the C. elegans death specification gene ces2. RESULTS: Mouse E4BP4 was ectopically expressed in CEM-C1-15 cells, resulting in sensitization to GC-evoked apoptosis in correlation with restoration of E4BP4 and Bim upregulation. shRNA mediated modest knockdown of E4BP4 in CEM-C7-14 cells resulted in concomitant reduction in Bim expression, although GC-evoked fold-induction and sensitivity to apoptosis was similar to parental cells. CONCLUSION: Data presented here suggest that GC-mediated upregulation of E4BP4 facilitates Bim upregulation and apoptosis of CEM cells. Since the Bim promoter does not contain any consensus GRE or EBPRE sequences, induction of Bim may be a secondary response. PMID- 21975220 TI - Effect of length of progesterone exposure during ovulatory wave development on pregnancy rate. AB - The objective was to determine the effects of the duration of progesterone exposure during the ovulatory wave on fertility (pregnancy rate) in beef cattle. We tested the hypothesis that short-progesterone exposure during the growing and early-static phase of the ovulatory follicle (analogous to the ovulatory wave of 3-wave cycles) is associated with higher fertility than a longer duration of exposure (analogous to the ovulatory wave of 2-wave cycles). Three to 5 days after ovulation, beef heifers (n = 172) and suckled beef cows (n = 193) were given an intravaginal progesterone-releasing device (CIDR) and 2.5 mg estradiol - 17beta +50 mg progesterone im to induce a new follicular wave. Cattle were allocated to short- or long-progesterone exposure groups (for 3 and 6 d after wave emergence, respectively) after which prostaglandin F(2alpha) was administered and CIDR were removed. Forty-eight hours later, all cattle were given 12.5 mg pLH and artificially inseminated (AI) with frozen-thawed semen. The diameter of the two largest follicles and the corpus luteum were measured by transrectal ultrasonography at CIDR removal, insemination, and 36 h after insemination. Pregnancy diagnosis was done ultrasonically 38 and 65 d post-AI. There was no difference in pregnancy rates in short- vs long-progesterone exposure in heifers (53 vs 47%, P = 0.44) or cows (63 vs 58%, P = 0.51). However, the diameter of the ovulatory follicle at CIDR removal and AI was smaller in short- than in long-progesterone groups (P < 0.02), and larger in cows than in heifers (P < 0.006). In conclusion, short-progesterone exposure during the growing and early-static phase of the ovulatory follicle (similar to 3-wave cycles) was not associated with higher fertility than a longer progesterone exposure (similar to 2-wave cycles). PMID- 21975221 TI - Blood manganese levels in patients with hepatic encephalopathy. AB - PROJECT: Hepatic encephalopathy is an increasingly common disease. Identification of prognosis risk factors in patients with liver damage may lead to preventive actions, towards decreasing its mortality. Manganese (Mn) levels are increased in basal ganglia of patients with hepatic encephalopathy as well as in cases of cirrhotic and liver failure patients. The present is a clinical, prospective, prolective and observational study developed at the Internal Medicine Service from "Dr. Dario Fernandez Fierro" General Hospital, ISSSTE, Mexico City. The objective of this work was to report whole blood Mn levels and mortality in encephalopathic patients. PROCEDURE: Consecutive patients over 18 years of age, diagnosed with hepatic encephalopathy were recruited at the emergency room service. An informed consent, signed by their families was collected. Patients' clinical characteristics, biochemical tests of renal function, hemoglobin, glucose, bilirubins and albumin levels were obtained along with a blood sample to analyze Mn. Patients evolution was followed up for 6 months. RESULTS: Blood Mn in patients [median, (range)] [20.5, (10.5-39.5) MUg/L] were higher than blood levels from a group of healthy volunteers [7.5, (6.1-12.8) MUg/L] (P<0.001). Among 9 patients studied four died, 2 women and 2 men, those patients showed higher (P=0.032) Mn levels [28, (17-39.5) MUg/L] than those alive [13.5, (10.5 32) MUg/L] after the follow up period. CONCLUSIONS: In this pilot study, Mn blood levels were higher in hepatic encephalopathy that died as consequence of the disease that those that survived in a 6 month follow up period. Blood Mn could be a potential prognosis factor for death in patients with hepatic encephalopathy. PMID- 21975223 TI - Identification of stromal proteins overexpressed in nodular sclerosis Hodgkin lymphoma. AB - Hodgkin lymphoma (HL) represents a category of lymphoid neoplasms with unique features, notably the usual scarcity of tumour cells in involved tissues. The most common subtype of classical HL, nodular sclerosis HL, characteristically comprises abundant fibrous tissue stroma. Little information is available about the protein composition of the stromal environment from HL. Moreover, the identification of valid protein targets, specifically and abundantly expressed in HL, would be of utmost importance for targeted therapies and imaging, yet the biomarkers must necessarily be accessible from the bloodstream. To characterize HL stroma and to identify potentially accessible proteins, we used a chemical proteomic approach, consisting in the labelling of accessible proteins and their subsequent purification and identification by mass spectrometry. We performed an analysis of potentially accessible proteins in lymph node biopsies from HL and reactive lymphoid tissues, and in total, more than 1400 proteins were identified in 7 samples. We have identified several extracellular matrix proteins overexpressed in HL, such as versican, fibulin-1, periostin, and other proteins such as S100-A8. These proteins were validated by immunohistochemistry on a larger series of biopsy samples, and bear the potential to become targets for antibody-based anti-cancer therapies. PMID- 21975224 TI - Reproduction opportunists in the new global sex trade: PGD and non-medical sex selection. AB - Regulatory differences between countries are an important driver of the cross border trade in assisted reproduction as people move to seek services unavailable in their home countries. The development of a lucrative global trade in non medical sex selection needs to be considered in ethical debates over its availability. I suggest that depictions of non-medical sex selection as a means of 'family balancing' or supportive of reproductive autonomy serve to distance the technologies rhetorically from the gender stereotyping inherent in their use and the commodification upon which they depend. They construct new social categories such as the 'unbalanced' family, the pathologization of 'gender disappointment' and a limited and highly individualized definition of reproductive freedom that permits medical interventions on healthy bodies. Orientalism pervades ethical debate depicting non-medical sex selection in the West as more acceptable to practices in 'Asia'. A case study of the interconnections between Australia and Thailand highlights the global economy sustaining the practice. PMID- 21975226 TI - Biosensor microprobes with integrated microfluidic channels for bi-directional neurochemical interaction. AB - This paper reports on silicon-based microprobes, 8 mm long and 250 um * 250 um cross-section, comprising four recessed biosensor microelectrodes (50 um * 150 um) per probe shank coated with an enzymatic layer for the selective detection of choline at multiple sites in brain tissue. Integrated in the same probe shank are up to two microfluidic channels for controlled local liquid delivery at a defined distance from the biosensor microelectrodes. State-of-the-art silicon micromachining processing was applied for reproducible fabrication of these experiment-tailored multi-functional probe arrays. Reliable electric and fluidic interconnections to the microprobes are guaranteed by a custom-made holder. The reversible packaging method implemented in this holder significantly reduces cost and assembly time and simplifies storage of the biosensor probes between consecutive experiments. The functionalization of the electrodes is carried out using electrochemically aided adsorption. This spatially controlled deposition technique enables a parallel deposition of membranes and is especially useful when working with microelectrode arrays. The achieved biosensors show adequate characteristics to detect choline in physiologically relevant concentrations at sufficient temporal and spatial resolution for brain research. Sensitivity to choline better than 10 pA um(-1), detection limit below 1 uM and response time of 2 s were obtained. The proposed combination of biosensors and microfluidic injectors on the same microprobe allows simultaneous chemical stimulation and recording as demonstrated in an agarose gel-based brain phantom. PMID- 21975225 TI - Wolbachia infections that reduce immature insect survival: predicted impacts on population replacement. AB - BACKGROUND: The evolutionary success of Wolbachia bacteria, infections of which are widespread in invertebrates, is largely attributed to an ability to manipulate host reproduction without imposing substantial fitness costs. Here, we describe a stage-structured model with deterministic immature lifestages and a stochastic adult female lifestage. Simulations were conducted to better understand Wolbachia invasions into uninfected host populations. The model includes conventional Wolbachia parameters (the level of cytoplasmic incompatibility, maternal inheritance, the relative fecundity of infected females, and the initial Wolbachia infection frequency) and a new parameter termed relative larval viability (RLV), which is the survival of infected larvae relative to uninfected larvae. RESULTS: The results predict the RLV parameter to be the most important determinant for Wolbachia invasion and establishment. Specifically, the fitness of infected immature hosts must be close to equal to that of uninfected hosts before population replacement can occur. Furthermore, minute decreases in RLV inhibit the invasion of Wolbachia despite high levels of cytoplasmic incompatibility, maternal inheritance, and low adult fitness costs. CONCLUSIONS: The model described here takes a novel approach to understanding the spread of Wolbachia through a population with explicit dynamics. By combining a stochastic female adult lifestage and deterministic immature/adult male lifestages, the model predicts that even those Wolbachia infections that cause minor decreases in immature survival are unlikely to invade and spread within the host population. The results are discussed in relation to recent theoretical and empirical studies of natural population replacement events and proposed applied research, which would use Wolbachia as a tool to manipulate insect populations. PMID- 21975227 TI - [New oral anticoagulant agents and atrial fibrilation]. PMID- 21975228 TI - [Systolic blood pressure and functional outcome in patients with acute stroke: a Mexican registry of acute cerebrovascular disease (RENAMEVASC)]. AB - OBJECTIVE: To analyze the association between the admission systolic blood pressure (SBP) and 30-day outcome in patients with acute cerebrovascular disease. METHODS: The REgistro NAcional Mexicano de Enfermedad VAScular Cerebral (RENAMEVASC) is a hospital-based multicenter registry performed between November 2002 and October 2004. A total of 2000 patients with clinical syndromes of acute cerebrovascular disease confirmed by neuroimaging were registered. The modified Rankin scale was used for outcome stratification. RESULTS: We analyzed 1721 patients who had registered their SBP: 78 (4.5%) had transient ischemic attack, 894 (51.9%) brain infarction, 534 (30.9%) intracerebral hemorrhage, 165 (9.6%) subarachnoid hemorrhage and 50 (2.9%) cerebral venous thrombosis. Among 1036 (60.2%) patients with the antecedent of hypertension, only 32.4% had regular treatment. The 30-day case fatality rate presented a J pattern with respect to SBP, so that the risk of death was highest in <100 mmHg (37.5%), decreased between 100 and 139, and reached gradually a new zenith in ?220 mmHg (35.3%). The best functional outcome corresponded to patients who had SBP between 100 mmHg and 159 mmHg. In a Cox proportional hazards model, SBP <100 mmHg or ?220 mmHg was an independent risk factor for 30-day mortality (RR: 1.52, IC 95%: 1.07 - 2.15), as well as the antecedent of hypertension (RR: 1.33, IC 95%: 1.06 - 1.65) and age >65 years (RR: 2.16, IC 95%: 1.74 - 2.67). CONCLUSION: Both hypotension and significant arterial hypertension at hospital admission are associated with an adverse outcome after acute cerebrovascular disease. Nevertheless, a good functional outcome can be attained in a wide range of SBP. PMID- 21975229 TI - [Systolic blood pressure and functional outcome in patients with acute stroke: a Mexican registry of acute cerebrovascular disease (RENAMEVASC)]. PMID- 21975230 TI - [Congenital heart disease: surgical results in a public hospital in Argentina]. AB - OBJECTIVE: To describe the results of congenital heart surgery at the Hospital de Pediatria J. P.Garrahan. METHODS: Between 2004 and 2009, 2942 patients, median age 2.5 years (1 d to 22.5 y), median weight 11.5 kg (1.6 kg to 96 kg), and 84% with cardiopulmonary bypass, were analyzed. Adjusted mortality risk analysis using RACHS and Aristotle score was performed. Newborn surgery and one stage repair in Fallot and ventricular septal defect with coarctation were analyzed as subgroupes. RESULTS: Mortality was 5.5%. Required mechanical ventilation 45%, 5% peritoneal dialysis, 12% delayed sternal closure and 8.4% reoperation. Twenty five percent with previous surgery, and 10% in poor clinical conditions. RACHS-1 categories morality distribution were 0.4% in one, 2.4% in two, 7.1% in three, 14% in four y 34 % in 5 and 6. One stage repair was performed in 84% of Fallots and 90% of ventricular septal defects with coarctation, with 3.2% and 10% mortality rate respectively. Two hundred and five newborns were operated with cardiopulmonary bypass with a mortality rate of 15% in the last year. CONCLUSIONS: Almost every congenital heart disease can be repaired without previous palliation, with satisfactory results in our institution. Poor clinical conditions significantly increased morbidity and mortality. PMID- 21975231 TI - Design and implementation of the TRACIA: intracoronary autologous transplant of bone marrow-derived stem cells for acute ST elevation myocardial infarction. AB - OBJECTIVE: To describe the design of a protocol of intracoronary autologous transplant of bone marrow-derived stem cells for acute ST-elevation myocardial infarction (STEMI) and to report the safety of the procedure in the first patients included. METHODS: The TRACIA study was implemented following predetermined inclusion and exclusion criteria. The protocol includes procedures such as randomization, bone marrow retrieval, stem cells processing, intracoronary infusion of stem cells in the infarct-related artery, preand- post MRI, pre-and-post SPECT with radioisotope ventriculography, and clinical follow up at 6 months. RESULTS: Eight patients with a diagnosis of acute STEMI and duration of symptoms of ?24 hours that were perfused successfully through primary percutaneous coronary intervention (PPCI) with a LVEF of ?45% were assigned randomly to two groups (n = 4 each). One group treated with stem cells and the other corresponded to the control group. Neither death, re-infarction, no need for revascularization or thrombosis of the stent were observed at follow-up. CONCLUSIONS: The initial experience at the Instituto Nacional de Cardiologia Ignacio Chavez in the treatment of acute STEMI by means of autologous transplantation of bone marrow-derived stem cells is encouraging. Implementation was possible in the first eight patients with no complications. PMID- 21975232 TI - [Oxidized LDL and anti-oxidized LDL antibodies according uric acid levels in overweight women]. AB - OBJECTIVE: To establish whether increased serum uric acid is associated with higher levels of oxidized LDL (oxLDL), antibodies against human oxidized LDL (oxLDL Ab) and ratios of LDL oxidation in overweight women. METHODS: Cross sectional study that included 114 women with body mass index ? 25 kg/m2. We determined weight, height, waist circumference, blood pressure, glycemia, uric acid, lipid profile, creatinine, Apolipoprotein B (ApoB), oxLDL, oxLDL Ab, insulin and insulin resistance was estimated using HOMA. Body mass index, LDL associated ApoB, rates of LDL oxidation and tertiles of uric acid were calculated. Metabolic syndrome was defined using NCEP/ATP III criteria. RESULTS: Of the women studied 51.8% were overweight and the rest was classified as obese; 66.7% had metabolic syndrome. In the total group and overweight group, only the oxLDL/HDL cholesterol ratio was significantly higher in the last tertile of uric acid. The serum levels of circulanting oxLDL and oxLDL/cholesterol, oxLDL/HDL cholesterol, oxLDL/ApoB and oxLDL/ LDL-associated ApoB ratios were significantly higher among obese women located in the highest tertile of uric acid. Concentrations of oxLDL Ab and oxLDL/oxLDL Ab were not related to the uric acid. Serum uric acid and ApoB predicted the elevation of oxLDL. CONCLUSION: Increased serum uric acid was associated with more oxidation of LDL among obese women. This suggests the importance of regular monitoring of uric acid in overweight women. Prospective research should be conducted. PMID- 21975233 TI - [Clinical characteristics and treatment of ventricular septum rupture after acute myocardial infarction]. AB - OBJECTIVE: To identify the characteristics, management strategy and mortality of patients with acute myocardial infarction (AMI) and rupture of ventricular septum (RVS). METHODS: The study included 40 patients admitted during a period of 8 years, due to AMI complicated with RVS. RVS was confirmed by echocardiogram. The clinical characteristics, type of treatment and hospital mortality were evaluated. Variables were compared by Mann-Withney U tests or Fisher exact test. RESULTS: Patients were 64 years old (56 - 73), 67% men, 53% diabetes mellitus, 43% hypertension, 40% smokers. Treatments were medical (45%), surgical (38%) or Amplatzer (17%). Overall mortality was 65%, in conservative group was 45%, in surgery group 38%, and Amplatzer group 17% (p = 0.02), it was associated to shorter time between AMI and RVS (p <0.001) and shorter time between and treatment (p <0.001). All patients with Killipp Kimbal III or IV died. CONCLUSIONS: Currently there is no management strategy in RSV with demonstrated advantage over other strategies. The only marker with good prognosis could be a long time between rupture and treatment. It is likely that the indication of management of International guidelines does not apply to all patients and these should be stratified according to their hemodynamic status. PMID- 21975234 TI - [Prevalence of positive serology to Trypanosoma cruzi in patients with clinical diagnosis of dilated myocardiopathy in the state of Campeche]. AB - The prevalence of chronic Chagas' heart disease as a cause of dilated cardiomyopathy is unknown in the State of Campeche, Mexico. A study was conducted to determine the prevalence of positive serology for Trypanosoma cruzi in patients with clinical diagnosis of dilated cardiomyopathy. Of a total of 127 patients diagnosed with dilated cardiomyopathy, we studied 91 with two positive serological tests for T. cruzi. We identified 14 positive cases for a prevalence of 15 % of chronic Chagas' heart disease. This prevalence is similar to that reported for the rest of the Yucatan Peninsula. PMID- 21975235 TI - The role of pulmonary pressure/cardiac index to identify pulmonary hemodynamic responders to acute oxygen breathing pulmonary hypertension COPD patients. AB - OBJECTIVES: We sought to analyze exercise-derived mean pulmonary artery pressure (Mpap) - cardiac index (CI) - relationship to expand the concepts regarding its nature and to better identify pulmonary hemodynamic responders to acute oxygen breathing (AOB - 99.5%) in pulmonary hypertension (PH) - COPD patients. METHODS: mPAP/CI and extrapolated pressure (Pext) to zero flow were obtained breathing room air (BRA) and under AOB - 99.5% in 40 stable COPD patients with rest and exercise PH. Hemodynamic characteristics were analyzed for the entire cohort and separate for cases those with resting < or > 30 mmHg mPAP (cohort - A and B, respectively). RESULTS: mPAP/CI abnormal location, slope (Sp: 5.77; 95% CI: 5.02 6.52 mmHg/L min/m2) and Pext values (15.8 mmHg) were associated with hypoxemia/decreased mixed venous - PO2 and lung mechanics abnormalities. Hemodynamic conditions that did not change for Sp (5.47; 95% CI: 3.64 - 7.3 mmHg/L min/m2, p = 0.4) and Pext (15.7 mmHg, p = 0.2) associated with a mPAP/CI significantly decrease in parallel during AOB - 99.5%. For cohort - A, an averagemPAP decline (12.3 mmHg, p <0.004) associated with a slope decrease (from 6.02; 95% CI: 4.04 - 8 to 4.3; 95% CI: 4.11 - 4.49 mmHg/L min/m2, (p <0.008), mPAP/CI - 95% CI down-ward displacement and Pext decrease (from 8.58 +/- 3 to 4.7 +/- 1.4 mmHg, p <0.01) in relation to BRA were observed. For cohort-B, average mPAP and mPAP/CI - 95% CI location did not change, Sp show a trend to decrease (p = 0.08) and Pext significantly increase (from 12 +/- 2.9 to 20.6 +/- 4.9 mmHg, p <0.03) in relation to BRA. Under AOB - 99.5%, significant differences for mPAP/ CI - 95% CI location, average-mPAP (A: 19.5 +/- 6 vs. B: 41.2 +/- 11.5 mmHg, p <0.001) and Pext (A: 4.7 +/- 1.4 vs. B: 20.6 +/- 4.9 mmHg, p <0.001), without Sp change between cohorts A and B were documented. CONCLUSIONS: When exercise derived mPAP/CI is analyzed, valuable information for linearpulmonary vascular resistance - (LPVR) could be obtained for PH - COPD patients. mPAP/CI abnormalities not always reflect "pure arteriolar" increased LPVR for all PH-COPD patients. Hemodynamic benefit on the pulmonary circulation and right ventricular afterload could be expected with long-term oxygen therapy in resting <30 mmHg mPAP-PH-COPD patients. PMID- 21975236 TI - [Multiple cardiac rhabdomyoma associated to intrauterine death]. AB - Rhabdomyoma is the most common cardiac tumor detected during fetal life and childhood; nevertheless its incidence is very low. This is a histologically benign tumor, but in some cases may cause hemodynamic repercussion with date of low cardiac output, arrhythmias and exceptionally intrauterine death as occurred in our case, which was detected by obstetric ultrasound and fetal echocardiogram and corroborated by histological study. PMID- 21975237 TI - [Refractory, incomplete and atypical Kawasaki disease. Case report and review of the literature]. AB - We report the case of a 2 year 7 month old boy with the diagnosis of incomplete and atypical Kawasaki disease, whom showed only two of the classical criteria: fever and conjunctival injection without exudate, presenting clinical manifestations that are reported less often, such as gallbladder hydrops, aseptic meningitis, arthralgia, sterile pyuria, coronary aneurysms and myocardial ischemia. This patient had recurrent and refractory Kawasaki disease not responding to treatment with intravenous immunoglobulin and thus requiring steroids and immunosuppressive management. PMID- 21975238 TI - [Hemorrhagic complications of acute coronary syndromes treatment]. AB - Acute coronary syndromes represent a problem of public health. The main goal of the treatment includes early reperfusion and avoidance of recurrent ischemic events. For this, thrombolytic, anticoagulant and antiplatelet drugs are used and, although they clearly improve the ischemic prognosis, are also associated with bleeding. It is now clear that bleeding has a negative impact in the patient's evolution and that its treatment can be also detrimental. It is important to recognize patients at high bleeding risk and to choose the therapy with the best risk-benefit profile. If the patient develops bleeding, it should be identified and treated properly to minimize its negative impact in the patient's prognosis. PMID- 21975239 TI - [Genetic and genomic studies in the hypertension: an actualization of the genomic studies]. AB - The arterial hypertension is considered to be the main risk factor for myocardial infarction, heart failure, ventricular arrhythmias, kidney failure, blindness and other diseases. Arterial hypertension is a multifactorial disease derived from environmental, genetic, gender and ethnic factors. In recent years, the World Health Organization estimated that approximately 17.5 million of deaths were due to cardiovascular diseases worldwide and that this pathology will become the leading cause of death in the next decade. Data from the National Survey of Mexican Ministry of Health (2006), reported approximately 17 million hypertensive adults, equivalent to a prevalence of 30.8% among Mexican population. As a consequence, hypertension represents the leading cause of morbidity from 2000 to 2005 and is increasing in recent years. However, studies have failed to clearly identify the molecular and genetic mechanisms of this pathology so far. Nevertheless, using the new technologies for analysis of variants in the genome, several genes in different loci that confer susceptibility to develop hypertension have been identified. In this review we compared the different studies in genetics and genomics of the hypertension that have been made worldwide and in Mexico, with the aim of identifying important genes involved in susceptibility to the development of this pathology. PMID- 21975240 TI - [Paraoxonase: its multiple functions and pharmacological regulation]. AB - Homocysteine, a non-protein amino acid, important risk factor for atherosclerosis and thrombosis, causes dysfunction of vascular endothelial cells traduced in inadequate vasodilatation mechanism, is pro-inflammatory and induces endoplasmic reticulum stress. The more reactive conformation is the homocysteine thiolactone (HcyT), product to the nonspecific action of methionyl-tRNA synthetase, which is incorporated into proteins by disulfide bonds (S homocysteinilation) or amide bonds (N-homocysteinilation) affecting protein structure and function leading to cell toxicity, autoimmune responses and atherogenesis. The enzyme paraoxonase-1 (PON1), part of high density lipoprotein (HDL), had been studied only for its ability to hydrolyze organophosphate derivatives. But, more recently it has been attributed other important role. The enzyme activities are involving in protecting against the development of atherosclerosis, by preventing oxidation of lipoproteins and hydrolyze HcyT. There is growing evidence about the protective role of PON1 in vascular disease. Genetic factors (polymorphisms of the PON1), environmental and lifestyle influence their concentration and biological activity, but drugs used as cardioprotectives and lipid-lowering or others, such as antibiotics and steroids, are also important modulators. This review is an updated of the most prominent information on clinical and experimental studies for understanding the role of the PON-1 in the protection against development of atherosclerosis. PMID- 21975241 TI - [Evidence-based cardiology: practical applications from epidemiology. III. Diagnostic capacity of a clinical test]. AB - This article reviews different characteristics of validity in a clinical diagnostic test. In particular, we emphasize the likelihood ratio as an instrument that facilitates the use of epidemiologic concepts in clinical diagnosis. PMID- 21975242 TI - [Therapeutic adherence]. AB - The lack of adherence to treatment of chronic cardiovascular disease is a clinical problem. Goes beyond doctor-patient relationship to what's new in social and public health worldwide. There is no one solution, but the potential for broad collaboration to resolve it with doctors, patients and facilities that provide organized community action. The Mexican Society of Cardiology aware of its leading role in the affair has taken the initiative to master the problem. This article is the initial report containing a review of the literature and a qualitative research study. Has focused on the interpretation of statements organized discussion "on purpose" at the recent Congress of Cardiology. Stresses the need to organize, promote the culture of health, acting in the rehabilitation of the doctor patient relationship according to the new demands of modernity and radical changes. PMID- 21975243 TI - [Collaboration strategies for the Iberoamerican Cardiovascular Journals network]. PMID- 21975244 TI - [Other observations regarding the Jupiter study]. PMID- 21975245 TI - [Author's response]. PMID- 21975246 TI - [Beware from the dangers of the heart!]. PMID- 21975247 TI - [Abdo Bisteni Adem MD]. PMID- 21975248 TI - HIV risk and associations of HIV infection among men who have sex with men in peri-urban Cape Town, South Africa. AB - BACKGROUND: The HIV epidemic in Sub Saharan Africa has been traditionally assumed to be driven by high risk heterosexual and vertical transmission. However, there is an increasing body of data highlighting the disproportionate burden of HIV infection among MSM in the generalized HIV epidemics across of Southern Africa. In South Africa specifically, there has been an increase in attention focused on the risk status and preventive needs of MSM both in urban centers and peri-urban townships. The study presented here represents the first evaluation of HIV prevalence and associations of HIV infection among MSM in the peri-urban townships of Cape Town. METHODS: The study consisted of an anonymous probe of 200 men, reporting ever having had sex with another man, recruited through venue-base sampling from January to February, 2009. RESULTS: Overall, HIV prevalence was 25.5% (n = 51/200). Of these prevalent HIV infections, only 6% of HIV-1 infected MSM were aware of their HIV status (3/50). 0% of men reported always having safe sex as defined by always wearing condoms during sex and using water-based lubricants. Independent associations with HIV infection included inconsistent condom use with male partners (aOR 2.3, 95% CI 1.0-5.4), having been blackmailed (aOR 4.4, 95% CI 1.6-20.2), age over 26 years (aOR 4.2, 95% CI 1.6-10.6), being unemployed (aOR 3.7, 95% CI 1.5-9.3), and rural origin (aOR 6.0, 95% CI 2.2 16.7). Bisexual activity was reported by 17.1% (34/199), and a total of 8% (16/200) reported having a regular female partner. Human rights violations were common with 10.5% (n = 21/200) reporting having been blackmailed and 21.0% (n = 42/200) reporting being afraid to seek health care. CONCLUSIONS: The conclusions from this study include that a there is a high risk and underserved population of MSM in the townships surrounding Cape Town. The high HIV prevalence and high risk sexual practices suggest that prevalence will continue to increase among these men in the context of an otherwise slowing epidemic. These data further highlight the need to better characterize risk factors for HIV prevention and appropriate targeted combination packages of HIV interventions including biomedical, behavioural, and structural approaches to mitigate HIV risk among these men. PMID- 21975250 TI - The future of pharmacologic treatment for bladder pain syndrome/interstitial cystitis: lessons from a meta-analysis. PMID- 21975252 TI - Mechanics of jazz shoes and their effect on pointing in child dancers. AB - There has been little scientific investigation of the impact of dance shoes on foot motion or dance injuries. The pointed (plantar-flexed) foot is a fundamental component of both the technical requirements and the traditional aesthetic of ballet and jazz dancing. The aims of this study were to quantify the externally observed angle of plantar flexion in various jazz shoes compared with barefoot and to compare the sagittal plane bending stiffness of the various jazz shoes. Sixteen female recreational child dancers were recruited for 3D motion analysis of active plantar flexion. The jazz shoes tested were a split-sole jazz shoe, full-sole jazz shoe, and jazz sneaker. A shoe dynamometer measured the stiffness of the jazz shoes. The shoes had a significant effect on ankle plantar flexion. All jazz shoes significantly restricted the midfoot plantar flexion angle compared with the barefoot condition. The split-sole jazz shoe demonstrated the least restriction, whereas the full-sole jazz shoe the most midfoot restriction. A small restriction in metartarsophalangeal plantar flexion and a greater restriction at the midfoot joint were demonstrated when wearing stiff jazz shoes. These restrictions will decrease the aesthetic of the pointed foot, may encourage incorrect muscle activation, and have an impact on dance performance. PMID- 21975253 TI - The bucket and the searchlight: formulating and testing risk hypotheses about the weediness and invasiveness potential of transgenic crops. AB - The bucket and the searchlight are metaphors for opposing theories of the growth of scientific knowledge. The bucket theory proposes that knowledge is gained by observing the world without preconceptions, and that knowledge emerges from the accumulation of observations that support a hypothesis. There are many problems with this theory, the most serious of which is that it does not appear to offer a means to distinguish between the many hypotheses that could explain a particular set of observations. The searchlight theory proposes that preconceptions are unavoidable and that knowledge advances through the improvement of our preconceptions - our hypotheses - by continuous criticism and revision. A hypothesis is a searchlight that illuminates observations that test the hypothesis and reveal its flaws, and knowledge thereby increases through the elimination of false hypotheses. Research into the risks posed by the cultivation of transgenic crops often appears to apply the bucket theory; many data are produced, but knowledge of risk is not advanced. Application of the searchlight theory, whereby risk assessments test hypotheses that transgenic crops will not be harmful, seems to offer a better way to characterise risk. The effectiveness of an environmental risk assessment should not be measured by the size of the bucket of observations on a transgenic crop, but by the power of the risk hypothesis searchlights to clarify the risks that may arise from cultivation of that crop. These points are illustrated by examples of hypotheses that could be tested to assess the risks from transgenic crops and their hybrids becoming weeds or invading non-agricultural habitats. PMID- 21975251 TI - Trunk acceleration for neuroprosthetic control of standing: a pilot study. AB - This pilot study investigated the potential of using trunk acceleration feedback control of center of pressure (COP) against postural disturbances with a standing neuroprosthesis following paralysis. Artificial neural networks (ANNs) were trained to use three-dimensional trunk acceleration as input to predict changes in COP for able-bodied subjects undergoing perturbations during bipedal stance. Correlation coefficients between ANN predictions and actual COP ranged from 0.67 to 0.77. An ANN trained across all subject-normalized data was used to drive feedback control of ankle muscle excitation levels for a computer model representing a standing neuroprosthesis user. Feedback control reduced average upper-body loading during perturbation onset and recovery by 42% and peak loading by 29% compared with optimal, constant excitation. PMID- 21975249 TI - The impact of tumor multifocality on outcomes in patients treated with radical nephroureterectomy. AB - BACKGROUND: The prognostic impact of multifocal upper-tract urothelial carcinoma (UTUC) is poorly understood. OBJECTIVE: To investigate the association between tumor multifocality and clinicopathologic features and outcomes of UTUC in patients managed by radical nephroureterectomy (RNU). DESIGN, SETTING, AND PARTICIPANTS: The study included 2492 patients treated with either open or laparoscopic RNU. Tumor and patient characteristics included tumor stage, tumor grade, lymph node status, lymphovascular invasion (LVI), tumor architecture, tumor location, unifocal or multifocal disease, gender, age, history of bladder cancer (BCa), Eastern Cooperative Oncology Group (ECOG) performance status (PS), and adjuvant chemotherapy. tumor multifocality of UTUC was defined as the synchronous presence of multiple tumors in the renal pelvis or ureter. INTERVENTION: All patients were treated with either open or laparoscopic RNU. MEASUREMENTS: Univariable and multivariable models tested the effect of tumor multifocality on disease progression and cancer-specific mortality. RESULTS AND LIMITATIONS: Five hundred ninety patients (23.7%) had tumor multifocality at the time of RNU. The median follow-up was 45 mo (interquartile range [IQR]: 0-101). Tumor multifocality was significantly associated with a history of previous BCa (p=0.032), lymph node involvement (p=0.036), tumor location in the ureter (p=0.003), higher tumor stage (p<0.001), higher tumor grade (p<0.001), sessile tumor architecture (p=0.003), and LVI (p=0.001). In organ-confined patients, tumor multifocality was an independent predictor of both disease progression (hazard ratio [HR]: 1.43; p=0.019) and cancer-specific mortality (HR: 1.46; p=0.027). When assessed in all patients, tumor multifocality was associated with both disease progression and cancer-specific mortality in univariable (p=0.005 and p=0.006, respectively) but not in multivariable analyses (p=0.468 and p=0.798, respectively). The main limitation is the retrospective design of the study. CONCLUSIONS: Tumor multifocality is an independent prognosticator of disease progression and cancer-specific mortality in patients with organ-confined UTUC treated with RNU. Multifocal organ-confined patients with UTUC may need closer follow-up. Integration of tumor multifocality with other factors may help identify those patients who would benefit from multimodal therapy. PMID- 21975254 TI - The CINMa index: assessing the potential impact of GM crop management across a heterogeneous landscape. AB - While significant progress has been made on the modification of crops for the benefit of producers, the same cannot be said in regards to eliciting the potential impact that these crops may have on the wider landscape and the diversity of life therein. Management impacts can create difficulties when making policy, regulation and licensing decisions in those countries where agriculture has a significant social and ecological position in the landscape. To begin to gauge the potential impacts of the management of a selection of GM crops on an agricultural landscape, four key biodiversity stressors (Chemicals, Introgression, Nutrients and Management: CINMa) were identified and a grading system developed using published data. Upon application to five selected GM crops in a case study area, CINMa identifies areas in the wider landscape where biodiversity is likely to be negatively or positively impacted, as well as agricultural zones which may benefit from the land use change associated with the management of GM crops and their associated post market environmental monitoring. PMID- 21975255 TI - Cross-fertilization between genetically modified and non-genetically modified maize crops in Uruguay. AB - The cultivation of genetically modified (GM) Bt maize (Zea mays L.) events MON810 and Bt11 is permitted in Uruguay. Local regulations specify that 10% of the crop should be a non-GM cultivar as refuge area for biodiversity, and the distance from other non-GM maize crops should be more than 250 m in order to avoid cross pollination. However, the degree of cross-fertilization between maize crops in Uruguay is unknown. The level of adventitious presence of GM material in non-GM crops is a relevant issue for organic farming, in situ conservation of genetic resources and seed production. In the research reported here, the occurrence and frequency of cross-fertilization between commercial GM and non-GM maize crops in Uruguay was assessed. The methodology comprised field sampling and detection using DAS-ELISA and PCR. Five field-pair cases where GM maize crops were grown near non-GM maize crops were identified. These cases had the potential to cross fertilize considering the distance between crops and the similarity of the sowing dates. Adventitious presence of GM material in the offspring of non-GM crops was found in three of the five cases. Adventitious presence of event MON810 or Bt11 in non-GM maize, which were distinguished using specific primers, matched the events in the putative sources of transgenic pollen. Percentages of transgenic seedlings in the offspring of the non-GM crops were estimated as 0.56%, 0.83% and 0.13% for three sampling sites with distances of respectively 40, 100 and 330 m from the GM crops. This is a first indication that adventitious presence of transgenes in non-GM maize crops will occur in Uruguay if isolation by distance and/or time is not provided. These findings contribute to the evaluation of the applicability of the "regulated coexistence policy" in Uruguay. PMID- 21975256 TI - Using existing data to predict and quantify the risks of GM forage to a population of a non-target invertebrate species: a New Zealand case study. AB - Determining the effects of genetically modified (GM) crops on non-target organisms is essential as many non-target species provide important ecological functions. However, it is simply not possible to collect field data on more than a few potential non-target species present in the receiving environment of a GM crop. While risk assessment must be rigorous, new approaches are necessary to improve the efficiency of the process. Utilisation of published information and existing data on the phenology and population dynamics of test species in the field can be combined with limited amounts of experimental biosafety data to predict possible outcomes on species persistence. This paper presents an example of an approach where data from laboratory experiments and field studies on phenology are combined using predictive modelling. Using the New Zealand native weevil species Nicaeana cervina as a case study, we could predict that oviposition rates of the weevil feeding on a GM ryegrass could be reduced by up to 30% without threat to populations of the weevil in pastoral ecosystems. In addition, an experimentally established correlation between feeding level and oviposition led to the prediction that a consistent reduction in feeding of 50% or higher indicated a significant risk to the species and could potentially lead to local extinctions. This approach to biosafety risk assessment, maximising the use of pre-existing field and laboratory data on non-target species, can make an important contribution to informed decision-making by regulatory authorities and developers of new technologies. PMID- 21975257 TI - Developing biosafety risk hypotheses for invertebrates exposed to GM plants using conceptual food webs: a case study with elevated triacylglyceride levels in ryegrass. AB - Regulators are acutely aware of the need for meaningful risk assessments to support decisions on the safety of GM crops to non-target invertebrates in determining their suitability for field release. We describe a process for developing appropriate, testable risk hypotheses for invertebrates in agroecosystems that might be exposed to plants developed by GM and future novel technologies. An existing model (PRONTI) generates a ranked list of invertebrate species for biosafety testing by accessing a database of biological, ecological and food web information about species which occur in cropping environments and their potential interactions with a particular stressor (Eco Invertebase). Our objective in this contribution is to explore and further utilise these resources to assist in the process of problem formulation by identifying potentially significant effects of the stressor on the invertebrate community and the ecosystem services they provide. We propose that for high ranking species, a conceptual food web using information in Eco Invertebase is constructed, and using an accepted regulatory risk analysis framework, the likelihood of risk, and magnitude of impact for each link in the food web is evaluated. Using as filters only those risks evaluated as likely to extremely likely, and the magnitude of an effect being considered as moderate to massive, the most significant potential effects can be identified. A stepwise approach is suggested to develop a sequence of appropriate tests. The GM ryegrass plant used as the "stressor" in this study has been modified to increase triacylglyceride levels in foliage by 100% to increase the metabolisable energy content of forage for grazing animals. The high ranking "test" species chosen to illustrate the concept are New Zealand native species Wiseana cervinata (Walker) (Lepidoptera: Hepialidae), Persectania aversa (Walker) (Lepidoptera: Noctuidae), and the self-introduced grey field slug, Deroceras reticulatum (Muller). PMID- 21975258 TI - Geographical distribution of salmonella infected pig, cattle and sheep herds in Sweden 1993-2010. AB - BACKGROUND: The Swedish salmonella control programme covers the entire production chain, from feed to food. All salmonella serotypes are notifiable. On average, less than 20 cases of salmonella in food-producing animals are reported every year. In some situations, the cases would be expected to cluster geographically. The aim of this study was to illustrate the geographic distribution of the salmonella cases detected in pigs, cattle and sheep. METHODS: Data on all herds with pigs, cattle and sheep found to be infected with salmonella during the time period from 1993 to 2010 were obtained from the Swedish Board of Agriculture. Using the ArcGIS software, various maps were produced of infected herds, stratified on animal species as well as salmonella serotype. Based on ocular inspection of all maps, some were collapsed and some used separately. Data were also examined for temporal trends. RESULTS: No geographical clustering was observed for ovine or porcine cases. Cattle herds infected with Salmonella Dublin were mainly located in the southeast region and cattle herds infected with Salmonella Typhimurium in the most southern part of the country. Some seasonal variation was seen in cattle, but available data was not sufficient for further analyses. CONCLUSIONS: Analyses of data on salmonella infected herds revealed some spatial and temporal patterns for salmonella in cattle. However, despite using 18 years' of data, the number of infected herds was too low for any useful statistical analyses. PMID- 21975259 TI - Review of venous anatomy for venographic interpretation in chronic cerebrospinal venous insufficiency. AB - Chronic cerebrospinal venous insufficiency (CCSVI) represents a recently described condition that may potentially contribute to the symptoms experienced by patients with multiple sclerosis. The evaluation of a prospective patient for CCSVI often involves an invasive evaluation with venography of the internal jugular and azygos veins. The purpose of this article is to review the normal anatomy of the internal jugular, vertebral, and azygos veins, as an understanding of these veins is necessary for appropriate interpretation of the venograms obtained to evaluate patients for CCSVI. PMID- 21975260 TI - Diagnostic accuracy of 123I-FP-CIT (DaTSCAN) in dementia with Lewy bodies: a meta analysis of published studies. AB - PURPOSE: A systematic meta-analysis of published studies on the diagnostic accuracy of presynaptic dopaminergic imaging with 123I-FP-CIT (DaTSCAN) in dementia with Lewy bodies (DLB). METHODS: We included (a) studies in which DaTSCAN was performed in cases of diagnostic uncertainty to differentiate between DLB and non-DLB dementia and (b) studies of patients with already established diagnoses of DLB, non-DLB dementia, or normalcy, against which the diagnostic accuracy of DaTSCAN was tested. We applied fixed-effects Mantel-Haenszel and hierarchical logistic regression models for meta-analysis of the diagnostic test's accuracy. The pooled sensitivity, specificity and diagnostic odds ratio (DOR) were estimated. Heterogeneity among studies was estimated by calculating the corresponding I2 statistic. We tested for publication or other bias by creating the respective funnel plot. RESULTS: Four studies, with a total of 419 subjects, were judged to be suitable for meta-analysis. According to hierarchical models, the estimated pooled sensitivity of DaTSCAN in differentiating DLB versus no DLB was 86.5% [95% Confidence Intervals (CI): 72-94.1%], the specificity was 93.6% (95% CI: 88.5-96.6%), and the DOR was 94.2 (95% CI: 25.7-345). The Mantel Haenszel estimate of overall DOR was calculated at 48.95 (95% CI: 26.16-91.59). There was some heterogeneity among studies (I2 = 45%), but this was not found statistically significant (chi2 test for heterogeneity p value = 0.142). Funnel plot analysis showed no significant bias. CONCLUSION: Allowing for the small number of studies in the meta-analysis, our results showed high diagnostic accuracy of DaTSCAN in DLB diagnosis, especially in terms of specificity. PMID- 21975261 TI - Cognitive impairment is common in Parkinson's disease without dementia in the early and middle stages in a Han Chinese cohort. AB - BACKGROUND: Cognitive impairments have been reported to be common in Parkinson's disease (PD) without dementia, which occur not only in the late stages of PD, but also in the early and middle stages. Until now, no reports on the profile of cognitive impairment in Chinese non-demented PD population have been published yet. Different ethnic groups should be assessed to improve evaluation of cognitive impairment in clinical practice. The aims of this study are to estimate the frequencies and profile of cognitive impairments and to explore the risk factors of cognitive impairments in Han Chinese non-demented PD patients at early and middle stages. METHODS: Eighty non-demented PD patients in early and middle stages and 86 healthy controls were invited to participate in this study. Neuropsychological batteries testing executive function, visuospatial function, memory and attention were evaluated. Cognitive impairments were defined as impaired performance in at least one cognitive domain. RESULTS: Neuropsychological batteries detected 30 cases with executive dysfunction, 27 cases with memory impairment, eight cases with visuospatial dysfunction and seven cases with attention impairment. As many as 48 cases (60%) of PD patients presented cognitive impairment. Logistic regression analysis indicated that education level and Hoehn & Yahr stage were associated with cognitive impairment in PD. CONCLUSIONS: Cognitive impairment is common in the early and middle stages of PD without dementia; executive function is the most common domain impaired in a Chinese PD population. Cognitive impairment might be predicted by lower education level and higher Hoehn and Yahr stage. PMID- 21975262 TI - Loss of ability to work and ability to live independently in Parkinson's disease. AB - OBJECTIVE: Ability to work and live independently is of particular concern for patients with Parkinson's disease (PD). We studied a series of PD patients able to work or live independently at baseline, and evaluated potential risk factors for two separate outcomes: loss of ability to work and loss of ability to live independently. METHODS: The series comprised 495 PD patients followed prospectively. Ability to work and ability to live independently were based on clinical interview and examination. Cox regression models adjusted for age and disease duration were used to evaluate associations of baseline characteristics with loss of ability to work and loss of ability to live independently. RESULTS: Higher UPDRS dyskinesia score, UPDRS instability score, UPDRS total score, Hoehn and Yahr stage, and presence of intellectual impairment at baseline were all associated with increased risk of future loss of ability to work and loss of ability to live independently (P <= 0.0033). Five years after initial visit, for patients <=70 years of age with a disease duration <=4 years at initial visit, 88% were still able to work and 90% to live independently. These estimates worsened as age and disease duration at initial visit increased; for patients >70 years of age with a disease duration >4 years, estimates at 5 years were 43% able to work and 57% able to live independently. CONCLUSIONS: The information provided in this study can offer useful information for PD patients in preparing for future ability to perform activities of daily living. PMID- 21975263 TI - What determines resilience in patients with Parkinson's disease? AB - OBJECTIVE: To investigate the relationship of resilience to disease severity, disability, quality of life (QoL) and non-motor symptoms in Parkinson's disease (PD). A secondary objective was to investigate whether resilience is distinct from other personality domains in PD. BACKGROUND: Resilience is the ability to reestablish emotional equilibrium in the face of adversity. It may play a pivotal role in disability and quality of life and has not been studied in PD. METHODS: 83 PD patients (Age 66.3 +/- 10.6, Total Unified Parkinson's Disease Rating Scale (T-UPDRS) 36.9 +/- 17.8) completed the Resilience Scale 15 (RS-15). Scales measuring disability, mental and physical health-related QoL, non-motor symptoms (depression, anxiety, somatization, apathy, fatigue), and personality domains were completed. Pearson's correlations were analyzed between these scales and the RS-15. RESULTS: Greater resilience correlated with less disability (r = -.30, p = .01), and better physical and mental QoL (r = .31, p < .01; r = .29, p = .01), but not with PD severity (T-UPDRS, r = -.17, p > .05). Among non-motor symptoms and personality domains, resilience strongly correlated with less apathy (r = .66), less depression (r = -.49), and more optimism (r = .54, all p < .001). Moderate correlations were seen between more resilience, reduced fatigue (r = .40) and anxiety (r = -.34; both p < .001). CONCLUSIONS: Resilience correlated with less disability and better QoL but not with PD severity. Resilience was also highly associated with both non-motor symptoms (less apathy, depression, fatigue) and a personality domain (more optimism). The role of resilience in helping patients adapt to living with symptoms of chronic disease may explain its lack of correlation with PD severity. PMID- 21975264 TI - Functional electrical stimulation for the treatment of lower extremity dystonia. PMID- 21975265 TI - Plasma proteome changes associated with refractory cytopenia with multilineage dysplasia. AB - BACKGROUND: Refractory cytopenia with multilineage dysplasia (RCMD) is a subgroup of myelodysplastic syndrome (MDS), which belongs to oncohematological diseases, occurring particularly in elderly patients, and represents a heterogeneous group of bone marrow diseases. The goal of this study was to look for plasma proteins that changed quantitatively or qualitatively in RCMD patients. RESULTS: A total of 46 plasma samples were depleted, proteins were separated by 2D SDS-PAGE (pI 4 7), and proteomes were compared using Progenesis SameSpots statistical software. Proteins were identified by nanoLC-MS/MS. Sixty-one unique, significantly (p < 0.05, ANOVA) different spots were found; proteins in 59 spots were successfully identified and corresponded to 57 different proteins. Protein fragmentation was observed in several proteins: complement C4-A, complement C4-B, inter-alpha trypsin inhibitor heavy chain H4, and endorepellin. CONCLUSIONS: This study describes proteins, which change quantitatively or qualitatively in RCMD patients, and represents the first report on significant alterations in C4-A and C4-B complement proteins and ITIH4 fragments in patients with MDS-RCMD. PMID- 21975266 TI - Predictors of outcome in a cognitive-behavioral group program for children and adolescents with social anxiety disorder. AB - The present study examined predictors of treatment outcome among children and adolescents with social anxiety disorder (SAD). Seventy-five participants (8-13 years) participated in a 12-session cognitive behavioral group treatment (CBT). Potential predictors were the pre-treatment severity of anxious symptoms assessed from both the child's and parent's perspective as well as depressive symptoms (child report only) and general emotional distress in parent (parent self report). Furthermore, the relationship between treatment outcome and child's self reported pre-post changes in self-consciousness and maladaptive anxiety regulation was investigated. Pre-treatment level of social anxiety reported by the child was a significant predictor for outcome, i.e. children with higher levels of social anxiety at pretreatment reported a greater reduction in social anxiety at post-treatment. Reduction in self-consciousness and maladaptive anxiety regulation both predicted reduction in social anxiety, although not independently. The results suggest that tailoring intervention to include strategies for emotion regulation of anxiety may improve treatment outcome. PMID- 21975267 TI - Two is better than one. PMID- 21975268 TI - Hormonal contraception and HIV: an unanswered question. PMID- 21975271 TI - Should there be a (or any) limit to IVF cycles? A rejoinder to Stewart et al. PMID- 21975269 TI - Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study. AB - BACKGROUND: Hormonal contraceptives are used widely but their effects on HIV-1 risk are unclear. We aimed to assess the association between hormonal contraceptive use and risk of HIV-1 acquisition by women and HIV-1 transmission from HIV-1-infected women to their male partners. METHODS: In this prospective study, we followed up 3790 heterosexual HIV-1-serodiscordant couples participating in two longitudinal studies of HIV-1 incidence in seven African countries. Among injectable and oral hormonal contraceptive users and non-users, we compared rates of HIV-1 acquisition by women and HIV-1 transmission from women to men. The primary outcome measure was HIV-1 seroconversion. We used Cox proportional hazards regression and marginal structural modelling to assess the effect of contraceptive use on HIV-1 risk. FINDINGS: Among 1314 couples in which the HIV-1-seronegative partner was female (median follow-up 18.0 [IQR 12.6-24.2] months), rates of HIV-1 acquisition were 6.61 per 100 person-years in women who used hormonal contraception and 3.78 per 100 person-years in those who did not (adjusted hazard ratio 1.98, 95% CI 1.06-3.68, p=0.03). Among 2476 couples in which the HIV-1-seronegative partner was male (median follow-up 18.7 [IQR 12.8 24.2] months), rates of HIV-1 transmission from women to men were 2.61 per 100 person-years in couples in which women used hormonal contraception and 1.51 per 100 person-years in couples in which women did not use hormonal contraception (adjusted hazard ratio 1.97, 95% CI 1.12-3.45, p=0.02). Marginal structural model analyses generated much the same results to the Cox proportional hazards regression. INTERPRETATION: Women should be counselled about potentially increased risk of HIV-1 acquisition and transmission with hormonal contraception, especially injectable methods, and about the importance of dual protection with condoms to decrease HIV-1 risk. Non-hormonal or low-dose hormonal contraceptive methods should be considered for women with or at-risk for HIV-1. FUNDING: US National Institutes of Health and the Bill & Melinda Gates Foundation. PMID- 21975273 TI - Child and adolescent suicide in the United States: a population at risk. PMID- 21975270 TI - DNA priming and influenza vaccine immunogenicity: two phase 1 open label randomised clinical trials. AB - BACKGROUND: Because the general population is largely naive to H5N1 influenza, antibodies generated to H5 allow analysis of novel influenza vaccines independent of background immunity from previous infection. We assessed the safety and immunogenicity of DNA encoding H5 as a priming vaccine to improve antibody responses to inactivated influenza vaccination. METHODS: In VRC 306 and VRC 310, two sequentially enrolled phase 1, open-label, randomised clinical trials, healthy adults (age 18-60 years) were randomly assigned to receive intramuscular H5 DNA (4 mg) at day 0 or twice, at day 0 and week 4, followed by H5N1 monovalent inactivated vaccine (MIV; 90 MUg) at 4 or 24 weeks, and compared with a two-dose regimen of H5N1 MIV with either a 4 or 24 week interval. Antibody responses were assessed by haemagglutination inhibition (HAI), ELISA, neutralisation (ID(80)), and immunoassays for stem-directed antibodies. T cell responses were assessed by intracellular cytokine staining. After enrolment, investigators and individuals were not masked to group assignment. VRC 306 and VRC 310 are registered with ClinicalTrials.gov, numbers NCT00776711 and NCT01086657, respectively. FINDINGS: In VRC 306, 60 individuals were randomly assigned to the four groups (15 in each) and 59 received the vaccinations. In VRC 310, of the 21 individuals enrolled, 20 received the vaccinations (nine received a two-dose regimen of H5N1 MIV and 11 received H5 DNA at day 0 followed by H5N1 MIV at week 24). H5 DNA priming was safe and enhanced H5-specific antibody titres following an H5N1 MIV boost, especially when the interval between DNA prime and MIV boost was extended to 24 weeks. In the two studies, DNA priming with a 24-week MIV boost interval induced protective HAI titres in 21 (81%) of 26 of individuals, with an increase in geometric mean titre (GMT) of more than four times that of individuals given the MIV-MIV regimen at 4 or 24 weeks (GMT 103-206 vs GMT 27-33). Additionally, neutralising antibodies directed to the conserved stem region of H5 were induced by this prime-boost regimen in several individuals. No vaccine-related serious adverse events were recorded. INTERPRETATION: DNA priming 24 weeks in advance of influenza vaccine boosting increased the magnitude of protective antibody responses (HAI) and in some cases induced haemagglutinin-stem-specific neutralising antibodies. A DNA-MIV vaccine regimen could enhance the efficacy of H5 or other influenza vaccines and shows that anti-stem antibodies can be elicited by vaccination in man. FUNDING: National Institutes of Health. PMID- 21975274 TI - Methicillin-resistant Staphylococcus aureus: new treatment guidelines for an old bug. PMID- 21975275 TI - Comparison of tiotropium plus fluticasone propionate/salmeterol with tiotropium in COPD: a randomized controlled study. AB - BACKGROUND: The combination of tiotropium and fluticasone propionate/salmeterol (FSC) is commonly used to treat chronic obstructive pulmonary disease (COPD), but no study had evaluated the effectiveness of tiotropium plus FSC with 250 MUg of fluticasone propionate. Our aim was to assess whether tiotropium (18 MUg once daily) plus FSC (250/50 MUg twice daily) provides better clinical outcomes compared to tiotropium monotherapy. METHODS: In this 24-week, randomized, open label, multicenter two-arm parallel study, 479 patients received tiotropium plus FSC (n = 237) or tiotropium alone (n = 242). RESULTS: After 24 weeks of treatment, the triple-inhaled treatment group had a significant improvement in pre-bronchodilator FEV(1) (L) compared to the tiotropium-only group (0.090 L vs. 0.038 L; P = 0.005). Regarding health-related quality of life, the mean change in total score on the St. George's Respiratory Questionnaire for COPD patients (SGRQ C) was -6.6 points in the tiotropium plus FSC group, but -1.5 points in the tiotropium-only group (P = 0.001). In the subgroup of GOLD stage II patients with COPD, treatment with tiotropium plus FSC also improved FEV(1) compared to tiotropium alone (0.088 L vs. 0.030 L; P = 0.011) and improved the total SGRQ-C score than tiotropium alone (-4.5 points vs. -1.0 points, respectively). This triple-inhaled treatment approach did not induce more adverse events, such as pneumonia. CONCLUSION: Over the course of 24 weeks, FSC (250/50 MUg twice daily) added to tiotropium provided greater improvement in lung function and quality of life in patients with COPD (FEV(1) <= 65%) than tiotropium alone. PMID- 21975277 TI - The health impact of social disadvantage in early childhood; the Generation R study. AB - Inequalities in child health are of major concern to policymakers, public health specialists and clinicians. This review of studies within the context of the Generation R study illustrates that inequalities in population health, at least partly, originate in pregnancy and early childhood. The review shows inequalities with regard to the health of the pregnant mother, with regard to the growth of the fetus, with regard to birth outcomes, and with regard to health indicators in early childhood. These results are shown with regard to both biological/somatic outcomes, as well as with regard to psychosocial outcomes and healthy lifestyles. Both socioeconomic inequalities and ethnic inequalities in health are present. Although some inequalities can be explained by known determinants, research needs to be done to reach a full understanding of the pathways between social disadvantage and ill health in early childhood. PMID- 21975276 TI - Shifts in cell-type expression accompany a diminishing role of spinal p38 mapkinase activation over time during prolonged postoperative pain. AB - BACKGROUND: Surgery often causes prolonged postoperative pain, the mechanisms of which are unknown. The authors investigated the role of p38, a pain-associated mitogen-activated protein kinase, in induction and maintenance of such pain. METHODS: Male rats were subjected to the skin-muscle incision retraction procedure at the saphenous region; the procedure causes ~4 weeks of secondary tactile hyperalgesia in the ipsilateral plantar region, indicating central sensitization. The spinal cord was sectioned from L3 and L4 + L5 vertebral segments and stained for activated p38 (P-p38) at postoperative day 3 (POD 3), just as secondary hyperalgesia develops; at PODs 10-12, the time of maximum hyperalgesia; and at POD 35, after the resolution of hyperalgesia. Some sections were costained for microglia, astrocytes, and neurons. Intrathecal injections of a P-p38 inhibitor were performed at POD 2 or POD 9, and subsequent changes in pain were monitored. RESULTS: Skin-muscle incision retraction increased the numbers of dorsal horn P-p38 positive cells in L3 by ~3-fold and in L4 + L5 by ~7 fold from POD 3 to PODs 11-12. This increase was accompanied by a shift from microglia to neurons, resulting in a ~20-fold increase in P-p38-positive neurons in L4-L5 over this time. No P-p38 was detected in astrocytes. A P-p38 inhibitor given at POD 2 prevented development of secondary hypersensitivity, but when given at POD 9 the same dose gave weak relief of pain for less than 3 h. CONCLUSIONS: Spinal P-p38 mitogen-activated protein kinase, activated after incision retraction, is important for the induction of prolonged pain, but despite increased pain near the time of maximum pain, its functional importance for the maintenance of pain is not great. PMID- 21975278 TI - Association between cocaine abuse in pregnancy and placenta-associated syndromes using propensity score matching approach. AB - AIMS: We used propensity scores matching techniques to assess the association between maternal cocaine abuse in pregnancy and the occurrence of placenta associated syndromes (PAS). STUDY DESIGN: Mothers who abused cocaine (n=5026) were matched to controls (n=5026) from a sample of 1,693,197, unexposed mothers in Florida from 1998 to 2007. Cocaine abuse was identified using the ICD-9 principal and secondary diagnosis codes (304.2 for cocaine dependence and 305.6 for cocaine abuse). The outcome of interest, PAS, was identified as any indication in diagnosis field of ICD-9-CM codes for: placental abruption (641.2), oligohydramnios (658.0), placental infarction (656.7, 656.8, 656.9), gestational hypertension (642.3, 642.9), preeclampsia (642.4, 642.5, and 642.7) or eclampsia (642.6). RESULTS: Nearly 6% of mothers in the study sample experienced a condition associated with PAS prior to matching. Women who abused cocaine were 58% more likely to have PAS when compared to women who did not (OR=1.48, 95% confidence interval: 1.33, 1.66). Women who abused cocaine were at elevated odds for placental abruption, placenta infarction and preeclampsia with the most pronounced odds noted for placental abruption (OR=2.79, 95% confidence interval: 2.19, 3.55). CONCLUSIONS: These findings indicate that cocaine abuse during pregnancy is associated with more placenta-related disorders than previously reported. PMID- 21975279 TI - Maternal pregnancy levels of trans-nonachlor and oxychlordane and prevalence of cryptorchidism and hypospadias in boys. AB - BACKGROUND: The etiologies of the male urogenital anomalies--cryptorchidism and hypospadias--are poorly understood. Given positive associations between chlordane isomers and testicular germ cell tumors, it is reasonable to assume that chlordanes might also be associated with other testicular dysgenesis syndrome disorders, namely cryptorchidism and hypospadias. OBJECTIVE: To examine whether exposure to in utero chlordane is related to cryptorchidism and hypospadias, we evaluated levels of chlordane derivatives, trans-nonachlor and oxychlordane, among pregnant women enrolled in the Collaborative Perinatal Project (CPP). METHODS: From 1959 to 1965, the CPP enrolled pregnant women at 12 U.S. medical centers. We analyzed serum trans-nonachlor and oxychlordane levels measured in third-trimester serum from the mothers of 217 sons with cryptorchidism, 197 sons with hypospadias, and 557 sons with neither condition. Adjusted odds ratios (ORs) and 95% confidence intervals were calculated using conditional logistic regression. RESULTS: The quartile-specific ORs for cryptorchidism or hypospadias show no notable associations with trans-nonachlor or oxychlordane. Further, there were no significant trends with increasing quartile of maternal trans-nonachlor or oxychlordane level in either cryptorchidism or hypospadias (p-trend all > 0.45). CONCLUSIONS: The results do not support an association between chlordane levels and cryptorchidism or hypospadias. It is unlikely that current chlordane exposure is related to the development of either anomaly, given that serum chlordane levels at the time of sample collection, the early 1960s, were considerably higher than levels at present. PMID- 21975280 TI - Accuracy assessment of CKC high-density surface EMG decomposition in biceps femoris muscle. AB - The aim of this study was to assess the accuracy of the convolution kernel compensation (CKC) method in decomposing high-density surface EMG (HDsEMG) signals from the pennate biceps femoris long-head muscle. Although the CKC method has already been thoroughly assessed in parallel-fibered muscles, there are several factors that could hinder its performance in pennate muscles. Namely, HDsEMG signals from pennate and parallel-fibered muscles differ considerably in terms of the number of detectable motor units (MUs) and the spatial distribution of the motor-unit action potentials (MUAPs). In this study, monopolar surface EMG signals were recorded from five normal subjects during low-force voluntary isometric contractions using a 92-channel electrode grid with 8 mm inter electrode distances. Intramuscular EMG (iEMG) signals were recorded concurrently using monopolar needles. The HDsEMG and iEMG signals were independently decomposed into MUAP trains, and the iEMG results were verified using a rigorous a posteriori statistical analysis. HDsEMG decomposition identified from 2 to 30 MUAP trains per contraction. 3 +/- 2 of these trains were also reliably detected by iEMG decomposition. The measured CKC decomposition accuracy of these common trains over a selected 10 s interval was 91.5 +/- 5.8%. The other trains were not assessed. The significant factors that affected CKC decomposition accuracy were the number of HDsEMG channels that were free of technical artifact and the distinguishability of the MUAPs in the HDsEMG signal (P < 0.05). These results show that the CKC method reliably identifies at least a subset of MUAP trains in HDsEMG signals from low force contractions in pennate muscles. PMID- 21975281 TI - Effects of ferulic acid on diabetic nephropathy in a rat model of type 2 diabetes. AB - Diabetic nephropathy is the most serious complication in diabetes mellitus. It is known that oxidative stress and inflammation play a central role in the development of diabetic nephropathy. In this study, we investigated that ferulic acid (FA) known as anti-oxidative agent could effect on diabetic nephropathy by anti-oxidative and anti-inflammatory mechanism. We examined the effects of FA in obese diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats. We treated FA to experimental rats from 26 to 45 weeks of age. We evaluated ACR, MDA and MCP-1 in 24 h urine and examined renal histopathology and morphologic change in extracted kidneys from rats. Also, we evaluated the ROS production and MCP-1 levels in cultured podocyte after FA treatment. In the FA-treated OLETF rats, blood glucose was significantly decreased and serum adiponectin levels were increased. Urinary ACR was significantly reduced in FA-treated OLETF rats compared with diabetic OLETF rats. In renal histopathology, FA-treated OLETF rats showed decreased glomerular basement membrane thickness, glomerular volume, and mesangial matrix expansion. FA treatment decreased oxidative stress markers and MCP-1 levels in 24 h urine of rats and supernatants of cultured podocyte. In conclusion, it was suggested that FA have protective and therapeutic effects on diabetic nephropathy by reducing oxidative stress and inflammation. PMID- 21975282 TI - Inhibition of NF-kappaB prevents high glucose-induced proliferation and plasminogen activator inhibitor-1 expression in vascular smooth muscle cells. AB - Recent epidemiologic studies clearly showed that early intensive glucose control has a legacy effect for preventing diabetic macrovascular complications. However, the cellular and molecular processes by which high glucose leads to macrovascular complications are poorly understood. Vascular smooth muscle cell (VSMC) dysfunction due to high glucose is a characteristic of diabetic vascular complications. Activation of nuclear factor-kappaB (NF-kappaB) may play a key role in the regulation of inflammation and proliferation of VSMCs. We examined whether VSMC proliferation and plasminogen activator inhibitor-1 (PAI-1) expression induced by high glucose were mediated by NF-kappaB activation. Also, we determined whether selective inhibition of NF-kappaB would inhibit proliferation and PAI-1 expression in VSMCs. VSMCs of the aorta of male SD rats were treated with various concentrations of glucose (5.6, 11.1, 16.7, and 22.2 mM) with or without an inhibitor of NF-kappaB or expression of a recombinant adenovirus vector encoding an IkappaB-alpha mutant (Ad-IkappaBalphaM). VSMC proliferation was examined using an MTT assay. PAI-1 expression was assayed by real-time PCR and PAI-1 protein in the media was measured by ELISA. NF-kappaB activation was determined by immunohistochemical staining, NF-kappaB reporter assay, and immunoblotting. We found that glucose stimulated VSMC proliferation and PAI-1 expression in a dose-dependent manner up to 22.2 mM. High glucose (22.2 mM) alone induced an increase in NF-kappaB activity. Treatment with inhibitors of NF-kappaB such as MG132, PDTC or expression of Ad-IkappaB-alphaM in VSMCs prevented VSMC proliferation and PAI-1 expression induced by high glucose. In conclusion, inhibition of NF-kappaB activity prevented high glucose-induced VSMC proliferation and PAI-1 expression. PMID- 21975284 TI - Lower extremity joint moments during carrying tasks in children. AB - Farm youth often carry loads that are proportionally large and/or heavy, and field measurements have determined that these tasks are equivalent to industrial jobs with high injury risks. The purpose of this study was to determine the effects of age, load amount, and load symmetry on lower extremity joint moments during carrying tasks. Three age groups (8-10 years, 12-14 years, adults), three load amounts (0%, 10%, 20% BW), and three load symmetry levels (unilateral large bucket, unilateral small bucket, bilateral small buckets) were tested. Inverse dynamics was used to determine maximum ankle, knee, and hip joint moments. Ankle dorsiflexion, ankle inversion, ankle eversion, knee adduction, and hip extension moments were significantly higher in 8-10 and 12-14 year olds. Ankle plantar flexion, ankle inversion, knee extension, and hip extension moments were significantly increased at 10% and 20% BW loads. Knee and hip adduction moments were significantly increased at 10% and 20% BW loads when carrying a unilateral large bucket. Of particular concern are increased ankle inversion and eversion moments for children, along with increased knee and hip adduction moments for heavy, asymmetrical carrying tasks. Carrying loads bilaterally instead of unilaterally avoided increases in knee and hip adduction moments with increased load amount. PMID- 21975285 TI - Building adherence-competent communities: factors promoting children's adherence to anti-retroviral HIV/AIDS treatment in rural Zimbabwe. AB - Given relatively high levels of adherence to HIV treatment in Africa, we explore factors facilitating children's adherence, despite poverty, social disruption and limited health infrastructure. Using interviews with 25 nurses and 40 guardians in Zimbabwe, we develop our conceptualisation of an 'adherence competent community', showing how members of five networks (children, guardians, community members, health workers and NGOs) have taken advantage of the gradual public normalisation of HIV/AIDS and improved drug and service availability to construct new norms of solidarity with HIV and AIDS sufferers, recognition of HIV-infected children's social worth, an ethic of care/assistance and a supporting atmosphere of enablement/empowerment. PMID- 21975287 TI - Multiplex polymerase chain reaction pathogen detection in patients with suspected septicemia after trauma, emergency, and burn surgery. AB - BACKGROUND: The goal of this study is to determine the clinical value of multiplex polymerase chain reaction (PCR) study for enhancing pathogen detection in patients with suspected septicemia after trauma, emergency, and burn surgery. PCR-based pathogen detection quickly reveals occult bloodstream infections in these high-risk patients and may accelerate the initiation of targeted antimicrobial therapy. METHODS: We conducted a prospective observational study comparing results for 30 trauma and emergency surgery patients to 20 burn patients. Whole-blood samples collected with routine blood cultures (BCs) were tested using a new multiplex, PCR-based, pathogen detection system. PCR results were compared to culture data. RESULTS: PCR detected rapidly more pathogens than culture methods. Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Multiple Organ Dysfunction (MODS) scores were greater in PCR-positive versus PCR-negative trauma and emergency surgery patients (P <= .033). Negative PCR results (odds ratio, 0.194; 95% confidence interval, 0.045-0.840; P = .028) acted as an independent predictor of survival for the combined surgical patient population. CONCLUSION: PCR detected the presence of pathogens more frequently than blood culture. These PCR results were reported faster than blood culture results. Severity scores were significantly greater in PCR-positive trauma and emergency surgery patients. The lack of pathogen DNA as determined by PCR served as a significant predictor of survival in the combined patient population. PCR testing independent of traditional prompts for culturing may have clinical value in burn patients. These results warrant further investigation through interventional trials. PMID- 21975286 TI - Adolescent physical activity and the built environment: a latent class analysis approach. AB - This study used latent class analysis to classify adolescent home neighborhoods (n=344) according to built environment characteristics, and tested how adolescent physical activity, sedentary behavior, and screen time differ by neighborhood type/class. Four distinct neighborhood classes emerged: (1) low-density retail/transit, low walkability index (WI), further from recreation; (2) high density retail/transit, high WI, closer to recreation; (3) moderate-high-density retail/transit, moderate WI, further from recreation; and (4) moderate-low density retail/transit, low WI, closer to recreation. We found no difference in adolescent activity by neighborhood class. These results highlight the difficulty of disentangling the potential effects of the built environment on adolescent physical activity. PMID- 21975288 TI - Lack of significant liver enzyme elevation and gallstones and/or sludge on ultrasound on day 1 of acute pancreatitis is associated with recurrence after cholecystectomy: a population-based study. AB - BACKGROUND: In a population-based study, we examined recurrence rates of acute pancreatitis (AP) after cholecystectomy performed to prevent recurrences of AP. METHODS: We abstracted data from medical records of all Olmsted county residents who underwent cholecystectomy at Mayo Clinic for the management of presumed gallstone or idiopathic AP between 1990 and 2005 (n = 239). Based on (i) significantly elevated liver enzymes (>=threefold increase of alanine aminotransferase or aspartate aminotransferase) on day 1 and (ii) the presence of gallstones/sludge in the gall bladder, we categorized patients into 4 groups: A (i + ii), B (i but not ii), C (ii but not i), and D (neither i nor ii). Recurrence rates of AP after cholecystectomy were determined in all groups. RESULTS: The median follow-up after cholecystectomy was 99 months (range, 8-220). AP recurred in 13 of 142 patients (9%) in group A, 1 of 17 patients (6%) in group B, 13 of 57 patients (23%) in group C, and 14 of 23 patients (61%) in group D (P < .0001 D vs. all other groups and P = .001 C vs. groups A and B). No difference was seen in recurrence rates in groups A vs. B (P = 1.0). Recurrences were more frequent in patients with normal liver enzymes (A + B vs. C + D; P = .000003) and in patients without sonographic evidence of gallstones/sludge (A + C vs. B + D; P = .0008). CONCLUSION: When AP is associated with significantly elevated liver enzymes on day 1, recurrence rates after cholecystectomy are low (9%). However, postcholecystectomy recurrence rates of AP are high in those without such laboratory abnormalities (34%), especially in those without gall bladder stones/sludge (61%) on abdominal ultrasonography. Our results raise doubts about the efficacy of cholecystectomy to prevent recurrent AP in patients with the absence of either a significant elevation of liver tests on day 1 of AP or gallstones and/or sludge in the gall bladder on initial ultrasound examination. PMID- 21975289 TI - The impact of CD4+ CD25+ T cells in the tumor microenvironment of hepatocellular carcinoma. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is the most common liver cancer. Therapeutic results are usually unsatisfactory because liver tumors recur often. Immunologic factors may be related to the recurrence of HCC; however, this possibility is mentioned only rarely. METHODS: Thirty HCC patients undergoing hepatectomies were divided into 3 groups according to the diameters of their HCCs: group A (n = 8), diameter <=3 cm; group B (n = 8), diameter >3 cm and <=5 cm; and group C (n = 14), diameter >5 cm. T-lymphocytes from peripheral blood, nontumor liver tissue, and the HCC were analyzed. RESULTS: The percentage of CD25+ in the CD4+ T cells did not differ between the peripheral blood and the nontumor liver tissue among the 3 groups. CD25+ cells were increased in the tumor tissue in group C patients (range, 6-41%; median, 22.9%; P = .003), compared to group A patients. The percentage of CD25+ in the CD4+ T cells in tumor tissue was positively correlated with tumor sizes (r = 0.556). These CD4+ CD25+ lymphocytes produced transforming growth factor-beta and interferon-gamma but not interleukin 10, and were anergic to plate-coated monoclonal antibodies (anti-CD3/anti-CD28). The characteristics of these antibodies were comparable to those of regulatory T cells. When the infiltration lymphocytes including CD4+ CD25+ T cells were added to the mixed lymphocyte reaction activated by autologous tumor lysate-pulsed dendritic cells, the proliferation of lymphocytes was inhibited. CONCLUSION: The increase of CD4+ CD25+ T cells in the tumor microenvironment correlates with tumor sizes. These CD4+ CD25+ regulatory T cells appeared to suppress the immune response activated by dendritic cells. PMID- 21975290 TI - Intraductal papillary mucinous neoplasm of the pancreas: associated cancers, family history, genetic predisposition? AB - BACKGROUND: High rates of extrapancreatic malignancies (EPM) have been observed in patients with intraductal papillary mucinous neoplasm (IPMN). IPMN in patients with familial pancreatic cancer have also been reported. Our purpose was to evaluate the association of IPMN with EPM, malignancies in family members, and germline BRCA1 and BRCA2 mutations. METHODS: Using retrospective analysis on prospectively collected data from 82 patients with IPMN and direct contact for familial cancer history, data were compared with those of 150 patients with pancreatic ductal adenocarcinoma (PDAC). The common germline mutations in the BRCA1 and BRCA2 genes were evaluated on available IPMN patients. RESULTS: EPM rates were greater in IPMN than PDAC patients (P = .002). Malignancies in first degree relatives, specifically pancreatic cancer, were more common among IPMN than PDAC patients (P = .028). IPMN patients with EPM had high rates of relatives with colorectal cancer (31%). Two of the 51 genetically tested patients (4%) were BRCA2 mutation carriers, and both had first-degree relatives with pancreatic cancer. One patient fulfilled the Amsterdam criteria for hereditary nonpolyposis colon cancer; however, the neoplasm was microsatellite stable. CONCLUSION: Our results demonstrated high rates of EPM among IPMN patients. There was an increased rate of cancer in families of IPMN patients, specifically pancreatic cancer. A high rate of colorectal cancer in families of IPMN patients who have EPM was also observed. These findings suggest a genetic component in the pathogenesis of IPMN. Possible genetic changes include BRCA2 mutations, which are found in 25% of IPMN patients with a family history of pancreatic cancer. PMID- 21975291 TI - Arginase inhibition promotes wound healing in mice. AB - OBJECTIVE: Arginase plays important regulatory roles in polyamine, ornithine, and nitric oxide syntheses. However, its role in the healing process has not been delineated. In this study, we used a highly potent and specific inhibitor of arginase, namely 2(S)-amino-6-boronohexanoic acid NH4 (ABH) to evaluate the role of arginase function in wound healing. MATERIALS AND METHODS: ABH or saline was applied topically to full thickness, dorsal, excisional wounds in C57BL/6 mice every 8 hours for 14 days post surgery and the rate of wound closure was estimated planimetrically. Wound tissue was harvested from mice sacrificed on postoperative days 3 and 7 and examined histologically. The extent of epithelial, connective, and granulation tissue present within the wound area was estimated histomorphometrically. The effect of ABH on wound arginase activity, production of nitric oxide metabolites (NO(x)), and presence of smooth muscle actin positive cells (myofibroblasts) was evaluated. RESULTS: While arginase activity was inhibited in vivo, the rate of wound closure significantly increased 7 days post surgery, (21 +/- 4%: P < .01; Student t test) in ABH treated animals. This was accompanied by an early increase in wound granulation tissue and accumulation of NO(x) followed by enhanced re-epithelialization and localization of myofibroblasts beneath the wound epithelium. CONCLUSION: Arginase inhibition improves excisional wound healing and may be used to develop therapeutics for early wound closure. PMID- 21975292 TI - Rates and patterns of death after surgery in the United States, 1996 and 2006. AB - BACKGROUND: Nationwide rates and patterns of death after surgery are unknown. METHODS: Using the Nationwide Inpatient Sample, we compared deaths within 30 days of admission for patients undergoing surgery in 1996 and 2006. International Classification of Diseases codes were used to identify 2,520 procedures for analysis. We examined the inpatient 30-day death rate for all procedures, procedures with the most deaths, high-risk cardiovascular and cancer procedures, and patients who suffered a recorded complication. We used logistic regression modeling to adjust 1996 mortality rates to the age and gender distributions for patients undergoing surgery in 2006. RESULTS: In 1996, there were 12,573,331 admissions with a surgical procedure (95% confidence interval [CI], 12,560,171 12,586,491) and 224,111 inpatient deaths within 30 days of admission (95% CI, 221,912-226,310). In 2006, there were 14,333,993 admissions with a surgical procedure (95% CI, 14,320,983-14,347,002) and 189,690 deaths (95% CI, 187,802 191,578). Inpatient 30-day mortality declined from 1.68% in 1996 to 1.32% in 2006 (P < .001). Of the 21 procedures with the most deaths in 1996, 15 had significant declines in adjusted mortality in 2006. Among these 15 procedures, 8 had significant declines in operative volume. The inpatient 30-day mortality rate for patients who suffered a complication decreased from 12.10% to 9.84% (P < .001). CONCLUSION: Nationwide reporting on surgical mortality suggests that the number of inpatient deaths within 30 days of surgery has declined. Additional research to determine the underlying causes for decreased mortality is warranted. PMID- 21975293 TI - An increase in endogenous erythropoietin concentrations has no cardioprotective effects in patients undergoing coronary artery bypass graft surgery. AB - OBJECTIVE: Preliminary data showed an increase in endogenous erythropoietin (EPO) concentrations after acute normovolemic hemodilution (ANH) in patients undergoing coronary artery bypass graft (CABG) surgery. Numerous studies have shown the organ protective properties of EPO. The aim of this study was to investigate the cardioprotective effects of these increased EPO concentrations that resulted from ANH during cardiac surgery. DESIGN: A prospective, randomized, blind study. SETTING: A university hospital. PARTICIPANTS: A total of 93 patients undergoing isolated CABG surgery with or without cardiopulmonary bypass (CPB). INTERVENTIONS: Subjects with CPB were randomized into the control (C) or ANH group. Those in the off-pump coronary artery bypass group underwent no treatment. In the ANH group, a precalculated amount of blood was withdrawn and replaced by colloids after the induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters were recorded intra- and postoperatively. Troponin concentrations were measured as a routine parameter postoperatively. Upon intensive care unit arrival, the EPO levels were higher in the ANH group than in the C group. There was no significant difference between the troponin values of the C and the ANH groups at 4 hours postoperatively. CONCLUSIONS: In patients undergoing CABG surgery on CPB, an increase in endogenous EPO concentrations in the physiologic range has no cardioprotective effects. PMID- 21975294 TI - Caspase-8 activity has an essential role in CD95/Fas-mediated MAPK activation. AB - Stimulation of CD95/Fas/APO-1 results in the induction of both apoptotic and non apoptotic signaling pathways. The processes regulating these two opposing pathways have not been thoroughly elucidated to date. In this study, using quantitative immunoblots, imaging, and mathematical modeling, we addressed the dynamics of the DED proteins of the death-inducing signaling complex (DISC), procaspase-8, and cellular FLICE inhibitory proteins (c-FLIPs) to the onset of CD95-mediated ERK1/2 and p38 mitogen-activated protein kinase (MAPK) activation. We found that CD95 DISC-induced caspase-8 activity is important for the initiation of ERK1/2 and p38 MAPK activation. The long c-FLIP isoform, c-FLIP(L), and the short c-FLIP isoform, c-FLIP(R), inhibited MAPK induction by blocking caspase-8 processing at the DISC. Furthermore, we built a mathematical model describing CD95 DISC-mediated MAPK activation and apoptosis. The model quantitatively defined the dynamics of DED proteins, procaspase-8, and c-FLIP, which lead to caspase-8 activation and induction of apoptotic and non-apoptotic signaling pathways. In conclusion, the combination of biochemical analysis with mathematical modeling provides evidence for an important role of caspase-8 in CD95-mediated activation of MAPKs, while c-FLIP exerts a regulatory function in this process. PMID- 21975295 TI - Hydrogen peroxide: a Jekyll and Hyde signalling molecule. AB - Reactive oxygen species (ROS) are a group of molecules produced in the cell through metabolism of oxygen. Endogenous ROS such as hydrogen peroxide (H2O2) have long been recognised as destructive molecules. The well-established roles they have in the phagosome and genomic instability has led to the characterisation of these molecules as non-specific agents of destruction. Interestingly, there is a growing body of literature suggesting a less sinister role for this Jekyll and Hyde molecule. It is now evident that at lower physiological levels, H2O2 can act as a classical intracellular signalling molecule regulating kinase-driven pathways. The newly discovered biological functions attributed to ROS include proliferation, migration, anoikis, survival and autophagy. Furthermore, recent advances in detection and quantification of ROS-family members have revealed that the diverse functions of ROS can be determined by the subcellular source, location and duration of these molecules within the cell. In light of this confounding paradox, we will examine the factors and circumstances that determine whether H2O2 acts in a pro-survival or deleterious manner. PMID- 21975297 TI - Solitary pulmonary nodule of benign metastasizing leiomyoma associated with primary lung cancer: a case report. AB - INTRODUCTION: Benign metastasizing leiomyoma in the lung is a very rare disease characterized by the growth of uterine leiomyoma tissue. In most cases there is a previous history of hysterectomy for uterine leiomyoma. CASE PRESENTATION: A 50 year-old Asian woman underwent a total abdominal hysterectomy for uterine leiomyoma at the age of 37 years old. She was referred to our hospital because of sudden anterior chest pain. A chest computed tomography scan revealed a ground glass opacity in her left S10 lung segment and a solitary small nodule in her left bronchial segment, S4. We performed a left lower lobectomy and an upper lung partial resection in order to make a definitive diagnosis and to enable us to determine a further therapeutic strategy. The ground-glass opacity in her left S10 was a primary lung adenocarcinoma, while the small nodule in her left S4 was diagnosed as a benign metastasizing leiomyoma. No additional therapy was done and our patient was followed up with chest computed tomography. Up to date, repetitive evaluation by chest computed tomography has shown no sign of benign metastasizing leiomyoma or lung cancer recurrence. CONCLUSION: This is a very rare case of benign metastasizing leiomyoma of the lung associated with primary lung cancer. This comorbid association should be considered in the differential diagnosis when a solitary lung nodule is detected in a patient with a history of uterine leiomyoma. PMID- 21975296 TI - Cytokine-dependent and cytokine-independent roles for Mcl-1: genetic evidence for multiple mechanisms by which Mcl-1 promotes survival in primary T lymphocytes. AB - Myeloid cell leukemia sequence-1 (Mcl-1) is a critical anti-apoptotic factor in T lymphocytes. However, in spite of the many pro-apoptotic proteins with proposed binding to Mcl-1, the specific interactions by which Mcl-1 regulates primary T cell survival under different conditions have not been fully explored. Further, how different trophic cytokines modulate the specific role(s) of Mcl-1 is unknown. Here, we use genetic mouse models to dissect the roles of Mcl-1 in primary T lymphocytes. Using the inducible Mcl-1-floxed estrogen receptor-Cre fusion protein (Mcl-1(f/f)ERCre) deletion system in combination with genetic modification of other B-cell lymphoma 2 (Bcl-2) family members, we show that loss of pro-apoptotic Bcl-2 homologous antagonist/killer (Bak) rescues the survival of Mcl-1-deficient T cells in the presence of IL-7. Without IL-7, the survival of Mcl-1-deficient cells cannot be rescued by loss of Bak, but is partially rescued by overexpression of Bcl-2 or loss of Bcl-2-interacting mediator of cell death (Bim). Thus, Mcl-1 and Bcl-2 have a shared role, the inhibition of Bim, in promoting T-cell survival during cytokine withdrawal. Finally, we show that other common gamma-chain (gammac) cytokines differentially modulate the roles of Mcl-1. IL-15 has effects similar to those of IL-7 in memory T cells and naive CD8(+) cells, but not naive CD4(+) cells. However, IL-4 maintains Mcl-1 and Bcl-2 but also upregulates Bim and Bcl-2-associated X protein (Bax), thus altering the cell's dependence on Mcl-1. PMID- 21975298 TI - An online diary for tracking epilepsy. AB - My Epilepsy Diary is a free Web-based application on the public website epilepsy.com, available for patients to track epilepsy and to aid clinicians with data-based, individualized management. The first aim of this descriptive study was to outline electronic diary functions. Second, the study retrospectively profiled a large cohort of 2010 calendar year diary users including demographics, seizure types, temporal distribution of seizures, triggers, and use and side effects of antiepileptic drugs (AEDs). A total of 1944 users provided demographic information and 1877 recorded seizure data. Most (64%) users were women. Average age was 29.9+/-16.0 years. A total of 70,990 seizure entries and 15,630 AED entries were logged. Events were apportioned as 79% seizures and 21% seizure clusters. Specific AEDs were detailed in 7331 entries: monotherapy was used in 18% and polytherapy in 82%. Mood-related side effects were most commonly reported in 19% of 1027 users. PMID- 21975299 TI - Heart rate variability measures as biomarkers in patients with psychogenic nonepileptic seizures: potential and limitations. AB - Heart rate variability (HRV) metrics provide reliable information about the functioning of the autonomic nervous system (ANS) and have been discussed as biomarkers in anxiety and personality disorders. We wanted to explore the potential of various HRV metrics (VLF, LF, HF, SDNN, RMSSD, cardiovagal index, cardiosympathetic index, approximate entropy) as biomarkers in patients with psychogenic nonepileptic seizures (PNES). HRV parameters were extracted from 3 minute resting single-lead ECGs of 129 subjects (52 with PNES, 42 with refractory epilepsy and 35 age-matched healthy controls). Compared with healthy controls, both patient groups had reduced HRV (all measures P<0.03). Binary logistic regression analyses yielded significant models differentiating between healthy controls and patients with PNES or patients with epilepsy (correctly classifying 86.2 and 93.5% of cases, respectively), but not between patients with PNES and those with epilepsy. Interictal resting parasympathetic activity and sympathetic activity differ between healthy controls and patients with PNES or those with epilepsy. However, resting HRV measures do not differentiate between patients with PNES and those with epilepsy. PMID- 21975300 TI - Home composting as an alternative treatment option for organic household waste in Denmark: An environmental assessment using life cycle assessment-modelling. AB - An environmental assessment of the management of organic household waste (OHW) was performed from a life cycle perspective by means of the waste-life cycle assessment (LCA) model EASEWASTE. The focus was on home composting of OHW in Denmark and six different home composting units (with different input and different mixing frequencies) were modelled. In addition, incineration and landfilling was modelled as alternatives to home composting. The most important processes contributing to the environmental impact of home composting were identified as greenhouse gas (GHG) emissions (load) and the avoided emissions in relation to the substitution of fertiliser and peat when compost was used in hobby gardening (saving). The replacement of fertiliser and peat was also identified as one of the most sensible parameters, which could potentially have a significant environmental benefit. Many of the impact categories (especially human toxicity via water (HTw) and soil (HTs)) were affected by the heavy metal contents of the incoming OHW. The concentrations of heavy metals in the compost were below the threshold values for compost used on land and were thus not considered to constitute a problem. The GHG emissions were, on the other hand, dependent on the management of the composting units. The frequently mixed composting units had the highest GHG emissions. The environmental profiles of the home composting scenarios were in the order of -2 to 16 milli person equivalents (mPE) Mg(-1) wet waste (ww) for the non-toxic categories and -0.9 to 28mPEMg(-1) ww for the toxic categories. Home composting performed better than or as good as incineration and landfilling in several of the potential impact categories. One exception was the global warming (GW) category, in which incineration performed better due to the substitution of heat and electricity based on fossil fuels. PMID- 21975301 TI - Benefits of supplementing an industrial waste anaerobic digester with energy crops for increased biogas production. AB - Currently, there is increasing competition for waste as feedstock for the growing number of biogas plants. This has led to fluctuation in feedstock supply and biogas plants being operated below maximum capacity. The feasibility of supplementing a protein/lipid-rich industrial waste (pig manure, slaughterhouse waste, food processing and poultry waste) mesophilic anaerobic digester with carbohydrate-rich energy crops (hemp, maize and triticale) was therefore studied in laboratory scale batch and continuous stirred tank reactors (CSTR) with a view to scale-up to a commercial biogas process. Co-digesting industrial waste and crops led to significant improvement in methane yield per ton of feedstock and carbon-to-nitrogen ratio as compared to digestion of the industrial waste alone. Biogas production from crops in combination with industrial waste also avoids the need for micronutrients normally required in crop digestion. The batch co digestion methane yields were used to predict co-digestion methane yield in full scale operation. This was done based on the ratio of methane yields observed for laboratory batch and CSTR experiments compared to full scale CSTR digestion of industrial waste. The economy of crop-based biogas production is limited under Swedish conditions; therefore, adding crops to existing industrial waste digestion could be a viable alternative to ensure a constant/reliable supply of feedstock to the anaerobic digester. PMID- 21975302 TI - Life Cycle Assessment of the MBT plant in Ano Liossia, Athens, Greece. AB - The aim of this paper is the application of Life Cycle Assessment to the operation of the MBT facility of Ano Liossia in the region of Attica in Greece. The region of Attica is home to almost half the population of Greece and the management of its waste is a major issue. In order to explicitly analyze the operation of the MBT plant, five scenarios were generated. Actual operation data of the MBT plant for the year 2008 were provided by the region of Attica and the LCA modeling was performed via the SimaPro 5.1 software while impact assessment was performed utilizing the Eco-indicator'99 method. The results of our analysis indicate that even the current operation of the MBT plant is preferable to landfilling. Among the scenarios of MBT operation, the one with complete utilization of the MBT outputs, i.e. compost, RDF, ferrous and non-ferrous metals, is the one that generates the most environmental gains. Our analysis indicates that the exploitation of RDF via incineration is the key factor towards improving the environmental performance of the MBT plant. Our findings provide a quantitative understanding of the MBT plant. Interpretation of results showed that proper operation of the modern waste management systems can lead to substantial reduction of environmental impacts and savings of resources. PMID- 21975303 TI - Changes in the expression of Toll-like receptors in the chicken testis during sexual maturation and Salmonella infection. AB - Rooster infertility is a major concern in the poultry industry and chicken male reproductive organs are the infectious tissues of various pathogenic microorganisms. Protection of the chicken male reproductive organs from pathogens is therefore an essential aspect of reproductive physiology. Recently Toll-like receptors (TLRs) have been identified as one of the key components of innate immunity in vertebrate species and have been reported to be expressed in the reproductive organs in various female species, including the chicken. However, mechanisms of antimicrobial protection of male reproductive organs mediated by TLRs are poorly understood. The objectives of this study were to determine the expression profile of the entire family of the ten chicken TLR genes in the chicken testis, to investigate whether sexual maturation affects their testicular mRNA abundance and to determine the changes in their expression levels in response to Salmonella enteritidis (SE) infection. RNA was extracted from the testis of healthy pre-pubertal, sexually mature and aged birds, and from sexually mature SE infected birds. RT-PCR analysis revealed that all TLRs, apart from TLR1 1 (TLR6), were expressed in the chicken testis. Quantitative real-time PCR analysis revealed that the testicular mRNA abundance of certain TLRs was developmentally regulated with respect to sexual maturation, while SE infection resulted in a significant induction of TLR2-1, 4, 5, 15 and 21 in the testis of sexually mature birds compared, to healthy birds of the same age. These findings provide strong evidence to suggest a key role of TLRs in the innate immune responses of chicken testis against Salmonella colonization. PMID- 21975304 TI - Reproductive gonadal steroidogenic activity in the fishing cat (Prionailurus viverrinus) assessed by fecal steroid analyses. AB - Non-invasive fecal steroid analyses were used to characterize gonadal activity in the fishing cat (Prionailurus viverrinus). Estrogen, progestagen and androgen metabolites were quantified in fecal samples collected for 12 months from four males and 10 females housed at seven North American zoological institutions. Male reproductive hormone concentrations did not vary (P>0.05) among season, and estrogen cycles were observed year-round in females and averaged (+/-SEM) 19.9+/ 1.0 days. Mean peak estrogen concentration during estrus (460.0+/-72.6ng/g feces) was five-fold higher than baseline (87.3+/-14.0ng/g feces). Five of seven females (71.4%) housed alone or with another female demonstrated spontaneous luteal activity (apparent ovulation without copulation), with mean progestagen concentration (20.3+/-4.7MUg/g feces), increasing nearly five-fold above baseline (4.1+/-0.8MUg/g feces). The non-pregnant luteal phase averaged 32.9+/-2.5 days (n=13). One female delivered kittens 70 days after natural mating with fecal progestagen concentrations averaging 51.2+/-5.2MUg/g feces. Two additional females were administered exogenous gonadotropins (150IU eCG; 100IU hCG), which caused hyper-elevated concentrations of fecal estrogen and progestagen (plus ovulation). Results indicate that: (1) male and female fishing cats managed in North American zoos are reproductively active year round; (2) 71.4% of females experienced spontaneous ovulation; and (3) females are responsive to exogenous gonadotropins for ovulation induction, but a regimen that produces a normative ovarian steroidogenic response needs to be identified. PMID- 21975305 TI - Effect of eCG on early resumption of ovarian activity in postpartum dairy cows. AB - The purpose of the present study was to hasten the resumption of ovarian activity early postpartum in lactating dairy cows, using equine chorionic gonadotropin (eCG), to enhance follicular growth, followed by hCG, to induce ovulation. Primiparous Holstein dairy cows (n=21) were assigned equally into eCG, eCG-hCG and Control groups. Cows in the eCG and eCG-hCG groups received an i.m. injection of eCG (500 IU Folligon(r)) on Day 6 postpartum. Cows in the eCG-hCG group were also given an i.m. injection of hCG (500 IU Chorulon(r)), once dominant follicle reached the diameter of 13-16 mm following eCG injection. Cows in Control group did not receive any treatment. Daily blood sampling and ultrasound examination were conducted, starting at Day 6 postpartum until confirming the third ovulation. Follicles >=10 mm in diameter were detected on Day 11.5+/-1.48, 10.1+/ 0.52 and 11.1+/-1.36 after calving in Control, eCG and eCG-hCG groups, respectively (P>0.05). The first wave dominant follicle ovulated in 71.4% of cows treated with eCG and eCG-hCG. In contrast, none of the first wave dominant follicles ovulated in Control cows. By Day 20 postpartum, all cows in eCG group, 6/7 cows in eCG-hCG group and none of the cows in Control group ovulated (P<0.05). Short estrous cycles (<=16 days) were detected in 2/7, 1/7 and 6/7 cows in eCG, eCG-hCG and control groups, respectively (P<0.05). In conclusion, injection of eCG on Day 6 postpartum could assist the early resumption of ovarian activity by enhancing ovarian follicle growth and early ovulation in postpartum cows. In this context, subsequent hCG injection may not provide any more beneficial effect. PMID- 21975306 TI - Effect of surface treatments on adhesion of low-fusing porcelain to titanium as determined by strain energy release rate. AB - OBJECTIVE: This study evaluated the effect of different chemical surface treatments on the surface characteristics of commercially pure titanium (cp Ti) and the adhesion of the porcelain-titanium system by means of strain energy release rate (G-value, J/m(2)). Surface roughness and morphology of treated cp Ti were additionally evaluated. METHODS: Two hundred and thirty specimens of machined cp Ti plates grade II were prepared. The specimens were divided into ten groups in each test according to the surface treatment used; Gr 1 (control; machined), Gr 2 (sandblasted), Gr 3 (CH(2)Cl(2) for 5 min), Gr 4 (CH(2)Cl(2) for 10 min), Gr 5 (10% H(2)O(2) for 5 min), Gr 6 (10% H(2)O(2) for 10 min), Gr 7 (30% H(2)O(2) for 5 min), Gr 8 (30% H(2)O(2) for 10 min), Gr 9 (9% HF for 5 min) and Gr 10 (9% HF for 10 min). Titanium-porcelain (Vita Titankeramik) was applied to each group for testing the adhesion. The G-value (J/m(2)) was measured with a four-point bending configuration. Following fracture testing specimens were examined with a scanning electron microscope (SEM). Surface roughness and SEM analysis were carried out. Data were analyzed using ANOVA and Tukey's test. RESULTS: Groups treated with 9% HF or CH(2)Cl(2) baths for 10 or 5 min showed the highest adhesion values (J/m(2)) (34.23+/-4.31, 30.75+/-4.91, 28.92+/-4.33 and 22.54+/-3.58) respectively among the groups. The machined groups demonstrated the lowest value (8.18+/-1.95) (J/m(2)). SEM analysis indicated a combination of cohesive and adhesive fractures for 9% HF, CH(2)Cl(2), sandblasted and 30% H(2)O(2) (10 min) groups, while mainly adhesive fractures were found with the other groups. There was no direct correlation between surface roughness and adhesion. SIGNIFICANCE: Adhesion between porcelain and cp Ti can be improved by the use of certain chemical surface treatments prior to porcelain firing as alternative techniques to sandblasting treatment. PMID- 21975307 TI - Failure responses of a dental porcelain having three surface treatments under three stressing conditions. AB - OBJECTIVES: Surface conditions are of interest in all-ceramic restorations since they can control both bonding and strength. Tensile testing methods are commonly used to evaluate surface conditions of ceramics. This work evaluated tensile properties of a feldspathic ceramic as-finished, sandblasted and etched under three stressing conditions: (1) biaxial flexure; (2) monotonic mastication loading, dry; and, (3) cyclic mastication loading, wet. MATERIALS AND METHODS: Feldspathic CAD/CAM blocks were sliced into Tabs 1mm thick, n=135 specimens were divided into 3 groups assigned to as-finished (600 grit SiC; control), sandblasted, and etched. Of the 45 specimens per group, 35 specimens were used for bonded tests and 10 specimens for biaxial flexure testing. Pin-on-three ball biaxial testing was performed per ISO 6872. 35 specimens were bonded to dentin analog bases and loaded to radial crack pop-in beneath a 3mm diameter piston. 20 specimens were tested dry with failure determined by acoustic emission methods. 15 specimens, bonded to bases having micro-channels for water transport, were cyclically loaded beneath the 3mm piston under water at 15Hz for 500,000 cycles. RESULTS: Biaxial flexure distinguished among all three surface conditions (p<0.05, ANOVA). Monotonic testing could not distinguish among groups. Cyclic testing could not distinguish between sandblasted and etched groups but both were weaker than as-finished. CONCLUSIONS: Mastication loading of bonded specimens creates a different stress state than simple flexure due to contributions of the cement-ceramic interface. Water adds a damage accumulation effect. Tensile stress conditions need to be chosen with the desired outcomes considered. PMID- 21975308 TI - Rosiglitazone enhances learning, place cell activity, and synaptic plasticity in middle-aged rats. AB - As an antidiabetic agent, rosiglitazone (ROSI) binds and activates peroxisome proliferator-activator receptor gamma (PPARgamma), altering the expression of genes involved in glucose uptake and disposal, ultimately affecting glucose regulation. ROSI might therefore be a potential treatment to ameliorate age related decline in cognitive function, particularly on an insulin-resistant background, where improvements in peripheral insulin sensitivity and central nervous system (CNS) glucose utilization may facilitate recovery of cognitive function. We therefore examined the amelioration potential of ROSI for neurocognitive deficits resulting from aging in an animal model. Behaviorally, acute and chronic ROSI treatments enhanced acquisition of learning in the water plus maze, a modified version of the Morris water maze task. In parallel, restoration of synaptic plasticity in the dentate gyrus of ROSI-treated middle aged rats was evident after a single dose intake. Additionally, the spatial receptive fields of hippocampal CA1 place cells were significantly improved by chronic ROSI administration. ROSI treatment reversed basal plasma insulin abnormalities and increased hippocampal glucose transporter (GLUT)-3 expression in middle-aged rats. Taken together, these results suggest that ROSI modulates hippocampal circuitry effectively to promote an improvement in cognitive function, possibly via a glucose transporter-3 mechanism. PMID- 21975310 TI - Slit ventricle syndrome after cyst-peritoneal shunting for the arachnoid cyst--a report of two cases. PMID- 21975309 TI - Research opportunities concerning youth and the Family Smoking Prevention and Tobacco Control Act. PMID- 21975311 TI - Persistent primitive first cervical intersegmental artery (proatlantal artery II) associated with subarachnoid hemorrhage of unknown origin. PMID- 21975312 TI - Gaze-independent brain-computer interfaces based on covert attention and feature attention. AB - There is evidence that conventional visual brain-computer interfaces (BCIs) based on event-related potentials cannot be operated efficiently when eye movements are not allowed. To overcome this limitation, the aim of this study was to develop a visual speller that does not require eye movements. Three different variants of a two-stage visual speller based on covert spatial attention and non-spatial feature attention (i.e. attention to colour and form) were tested in an online experiment with 13 healthy participants. All participants achieved highly accurate BCI control. They could select one out of thirty symbols (chance level 3.3%) with mean accuracies of 88%-97% for the different spellers. The best results were obtained for a speller that was operated using non-spatial feature attention only. These results show that, using feature attention, it is possible to realize high-accuracy, fast-paced visual spellers that have a large vocabulary and are independent of eye gaze. PMID- 21975313 TI - Neuronal and oscillatory activity during reward processing in the human ventral striatum. AB - Accumulated evidence from animal studies implicates the ventral striatum in the processing of reward information. Recently, deep brain stimulation (DBS) surgery has enabled researchers to analyze neurophysiological recordings from humans engaged in reward tasks. We present data recorded from the human ventral striatum during deep brain stimulation surgery as a participant played a video game coupled to the receipt of visual reward images. To our knowledge, we identify the first instances of reward-sensitive single unit activity in the human ventral striatum. Local field potential data suggest that alpha oscillations are sensitive to positive feedback, whereas beta oscillations exhibit significantly higher power during unrewarded trials. We report evidence of alpha-gamma cross frequency coupling that differentiates between positive and negative feedback. PMID- 21975314 TI - Lentivirus-mediated APP695-RNAi reduces apoptosis in APP transgenic mouse neurons. AB - Amyloid-beta peptide (Abeta) is a cleavage product of the amyloid precursor protein (APP), which is thought to be important in the pathogenesis of Alzheimer's disease (AD). Recent evidence suggests that Abeta induces neuronal apoptosis in the brain and in primary neuronal cultures. If decreased Abeta whether could reduce the neuronal apoptosis? In this study, APP695-siRNA was delivered to hippocampal and cortical neurons of APP695 transgenic mice (AD model) in vitro using a recombinant lentivirus vector. The results show that lentivirus-mediated RNA interference of the APP695 gene could reduce neuronal apoptosis, possibly through the reduction of caspase-3 activity and the neuronal apoptosis pathway. These results suggest that lentivirus-mediated RNA interference may be a potential therapeutic for AD. PMID- 21975316 TI - Medicare costs and surgeon supply in hospital service areas. AB - OBJECTIVE: To quantify the correlates of variations of Medicare per beneficiary costs at the hospital service area level and determine whether physician supply and the specialty of physicians has a significant relationship with cost variation. BACKGROUND: The American Medical Association Masterfile data on physician and surgeon location, characteristics and specialty; Census derived sociodemographic data from 2006 ZIP code level Claritas PopFacts database; and Medicare per beneficiary costs from the Dartmouth Atlas of Health Care project. METHODS: A correlational analysis using bivariate plots and fixed effects linear regression models controlling for hospital service area sociodemographics and the number and characteristics of the physician supply. Data were aggregated to the Dartmouth hospital service area level from ZIP code level files. RESULTS: We found that costs are strongly related to the sociodemographic character of the hospital service areas and the overall supply of physicians but a mixed correlation to the specialist supply depending on the interaction of the proportion of the physician supply who are international medical graduates. The ratio of general surgeons and surgical subspecialists to population are associated with lower costs in the models, again with difference depending on the influence of international medical graduates. There is a strong association between higher costs and the local proportion of physician supply made up of graduates of non-US or Canadian medical schools and female graduates. CONCLUSIONS: These results suggest that strategies to reduce overall costs by changing physician supply must consider more than just overall numbers. PMID- 21975315 TI - Cardiovascular risk factors and menstrual cycle phase in pre-menopausal women. AB - BACKGROUND: Exogenous estrogens have been shown to affect markers of cardiovascular risk in women. AIM: The objective of this study was to determine the effect of menstrual cycle phase on markers of cardiovascular risk in young, healthy women with regular menstrual cycles. SUBJECTS AND METHODS: This prospective cohort study examined 20 healthy pre-menopausal women at 2 time points in the menstrual cycle, in early follicular phase and early luteal phase. RESULTS: In the early luteal phase, levels of estrogen, progesterone, LH, total cholesterol, and HDL were significantly higher, compared with the early follicular phase. In contrast, there were no significant differences in LDL or triglyceride levels between the 2 phases. Furthermore, there were no significant effects of menstrual cycle phase on glycemic indices (fasting blood glucose, glycohemoglobin or homeostatic model assessment of insulin resistance), markers of inflammation (C-reactive protein, soluble CD40 ligand, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, or adiponectin), or vascular function, as measured by brachial artery reactivity. CONCLUSIONS: Although menstrual cycle phase affects total cholesterol and HDL levels, it does not affect other markers of cardiovascular risk in young women with regular menstrual cycles. PMID- 21975318 TI - Comparison of adjuvant systemic chemotherapy with or without hepatic arterial infusional chemotherapy after hepatic resection for metastatic colorectal cancer. AB - BACKGROUND: The potential benefit of adjuvant hepatic arterial infusional floxuridine (HAI-FUDR) in addition to modern systemic chemotherapy using oxaliplatin or irinotecan remains unknown for patients with resected liver confined colorectal metastases (CRLM). The principle aim of this study was to compare outcomes in patients receiving modern systemic chemotherapy with or without HAI-FUDR. METHODS: Between 2000 and 2005, 125 patients underwent resection of CRLM followed by adjuvant HAI-FUDR plus dexamethasone (Dex) and concurrent systemic chemotherapy including oxaliplatin or irinotecan. These patients were compared retrospectively to 125 consecutive patients who received modern systemic chemotherapy alone after liver resection. RESULTS: The median follow-up for all patients was 43 months. There were no differences in clinical risk score, disease-free interval, size of largest CRLM, number of CRLM, or prehepatectomy CEA level between the 2 groups. Adjuvant HAI-FUDR was associated with an improved overall and liver recurrence-free survival (liver RFS) and disease-specific survival (DSS). For the adjuvant HAI-FUDR group, the 5-year liver RFS, overall RFS, and DSS were 75%, 48%, and 79%, respectively, compared to 55%, 25%, and 55% for the systemic alone group (P < 0.01). On multivariate analysis, adjuvant treatment including HAI-FUDR was independently associated with improved liver RFS (HR = 0.34), overall RFS (HR = 0.65), and DSS (HR = 0.39), P < 0.01. CONCLUSIONS: Adjuvant HAI-FUDR combined with modern systemic chemotherapy is independently associated with improved survival compared to adjuvant systemic chemotherapy alone. A randomized clinical trial between these 2 regimens is justified. PMID- 21975317 TI - The use, safety and cost of bariatric surgery before and after Medicare's national coverage decision. AB - OBJECTIVE: To determine the impact of the Centers for Medicare and Medicaid Services' (CMS) bariatric surgery national coverage decision (NCD) on the use, safety, and cost of care CMS beneficiaries. BACKGROUND: In February 2006, the CMS issued a NCD restricting reimbursement for bariatric surgery to accredited centers and including coverage for laparoscopic adjustable gastric band (LAGB). METHODS: A pre/postinterrupted time-series cohort study using nationwide Medicare data (2004-2008) evaluating rates of bariatric procedures/100,000 enrollees, 90 day mortality, readmission rate and payments. RESULTS: Forty-seven thousand thirty patients underwent procedures at 928 sites pre-NCD and 662 post-NCD. The procedure rate/100,000 patients dropped after the NCD to 17.8 (from 21.9 in 2005) increasing to 23.8 and 29.1 in 2007 and 2008, respectively. Open roux-en-y gastric bypass (ORYGB) and laparoscopic roux-en-y gastric bypass (LRYGB) were common pre-NCD (56.0% ORYGB, 35.5% LRYGB) changing post-NCD with LAGB inclusion (12.8% ORYGB, 48.7% LRYGB, 36.7% LAGB). 90-day mortality pre-NCD was 1.5% (1.8% ORYGB, 1.1% LRYGB) and post-NCD was 0.7% (1.7% ORYGB, 0.8% LRYGB, 0.3% LAGB; P < 0.001). The 90-day rates of readmission decreased post-NCD (19.9% to 15.4%), reoperation (3.2% to 2.1%) and payments ($24,363 to $19,746; P for all <0.001). Differences in outcome and cost were largely explained by a shift in procedure type and patient characteristics. CONCLUSIONS: The NCD was associated with a temporary reduction in procedure rate and a shift in types of procedures and patients undergoing bariatric surgery. It was associated with a significant decrease in the risk of death, complications, readmissions, and per patient payments. PMID- 21975319 TI - Reliability of whole sentinel lymph node analysis by one-step nucleic acid amplification for intraoperative diagnosis of breast cancer metastases. AB - OBJECTIVE: To assess the reliability of using the One-Step Nucleic Acid Amplification (OSNA) assay as a single test on whole sentinel lymph nodes (SLN) as a method of intraoperative diagnosis and staging of SLNs in breast cancer. BACKGROUND: Combining histological and molecular assessment of metastasis on the same SLN may not fully reproduce the actual load of cancer cells present in the SLN and create problems in decisions regarding axillary dissection. METHODS: Selection criteria for the whole SLN OSNA test required that the primary tumor expressed CK19 in more than 80% of tumor cells. Imprint cytology analysis of SLNs was performed together with the OSNA. RESULTS: Of the 279 patients enrolled for SLN evaluation, 123 gave consent to the OSNA protocol and 156 to the standard histology. Thirteen patients were excluded from OSNA evaluation because of low CK19 gene expression in the primary tumor; only 2.3% were truly negative. The kappa of concordance between the imprint cytology and OSNA results was 0.52. The rate of macrometastases determined by OSNA was 11% versus 20% determined by histology, whereas the rate of OSNA-micrometastases (18%) was significantly higher than that determined by histology (8%). The rate of SLN-negative cases was similar between the 2 protocols. Macrometastases correlated with the presence of vascular invasion in both protocols. The rate of axillary lymph node metastases was consistent with SLN tumor load. CONCLUSIONS: Intraoperative OSNA assay performed on the whole SLN gave objective and reproducible results that were useful for directing decisions regarding axillary dissection and for accurately defining the SLN stage. PMID- 21975320 TI - Sentinel lymph node biopsy in patients with thin primary cutaneous melanoma. AB - OBJECTIVES: To determine the rate and clinicopathologic factors predictive of sentinel lymph node (SLN) positivity, regional lymph node recurrence, and survival in a large series of patients with thin primary cutaneous melanoma who underwent SLN biopsy (SLNB). METHODS: Patients with thin (<=1 mm) melanomas who underwent SLNB between 1992 and 2009 at Melanoma Institute Australia were identified from the Melanoma Institute Australia database. The association of clinicopathologic features with SLN status, lymph node recurrence, and survival was analyzed. RESULTS: In 432 patients [226 men, 206 women; median age 49.5 years (range: 14.4-85.0 years)], SLNB was positive for metastatic melanoma in 29 (6.7%) patients. No SLN positivity was detected in 37 patients with primary tumor thickness 0.50 mm or less. Breslow thickness (P = 0.012) and presence of lymphovascular invasion (P = 0.018) were the only factors significantly associated with SLN positivity. Regional lymph node recurrence was significantly more common in tumors located in the head/neck region (4/33, 12%) than in extremities (3/245, 1.2%) and trunk (2/154, 1.3%) (P < 0.001). Primary tumor mitotic rate was a significant predictor of melanoma-specific survival (Hazard Ratio [HR] = 1.2, 95% confidence interval: 1.09-1.35, P < 0.001). CONCLUSIONS: There is a low but significant rate of SLN positivity in patients with primary melanomas 0.51 to 1.0 mm in thickness. Given its prognostic importance, SLNB should be considered in such patients, particularly if there is lymphatic permeation by melanoma at the primary tumor site. More frequent regional node field recurrences in patients with head/neck primary tumors may be a consequence of complex lymphatic drainage patterns in this region. PMID- 21975321 TI - Case-matched outcomes in bariatric surgery for treatment of type 2 diabetes in the morbidly obese patient. AB - OBJECTIVE: To compare the relative efficacy of medical management, the duodenal switch (DS), and the laparoscopic adjustable gastric band (LAGB) to the Roux-en-Y gastric bypass (RYGB) for treatment of type 2 diabetes mellitus (T2DM). BACKGROUND: The RYGB resolves T2DM in a high proportion of patients and is considered the standard operation for T2DM resolution in morbidly obese patients. However, no data exist comparing the efficacy of medical management and other bariatric operations to the RYGB for treatment of T2DM in comparable patient populations. METHODS: We performed a retrospective case-matched study of morbidly obese patients with T2DM who had undergone medical management (nonsurgical controls [NSC]; N = 29), LAGB (N = 30), or DS (N = 27) and were compared with matched T2DM patients who had undergone RYGB. Matching was performed with respect to age, sex, body mass index, and hemoglobin A1C (HbA1C). Outcomes assessed were changes in body mass index, HbA1C, and diabetes medication scores at 1 year. RESULTS: The Roux-en-Y gastric bypass produced greater weight loss, HbA1C normalization, and medication score reduction compared to both NSC and LAGB matched cohorts. Duodenal switch produced greater reductions in HbA1C and medication score than RYGB, despite no greater weight loss at 1 year. Surgical complications were rarely life threatening. CONCLUSIONS: This study provides an important perspective about the comparative efficacy of LAGB, DS, and NSC to the RYGB for treatment of T2DM among obese patients. After 1 year of follow-up, RYGB is superior to NSC and LAGB with respect to weight loss and improvement in diabetes whereas DS is superior to RYGB in reducing HbA1C and medication score. PMID- 21975322 TI - Safety of intermittent Pringle maneuver cumulative time exceeding 120 minutes in liver resection: a further step in favor of the "radical but conservative" policy. AB - OBJECTIVE: We retrospectively compared the short-term outcome of a consecutive cohort of patients who underwent hepatectomy with intermittent clamping ranging between 60 and 120 minutes with those having a clamping time exceeding 120 minutes. BACKGROUND: Intermittent Pringle maneuver is widely used to minimize blood loss during hepatectomy, without an established time limit. However, many authors claim it is dangerous for patient outcome. MATERIAL AND METHODS: Among 426 consecutive patients who underwent hepatectomy, we retrospectively selected 189 whose intermittent clamping time exceeded 60 minutes: 117 of these had intermittent Pringle maneuver lasting less than 120 minutes (group 1) and 72 clamping time exceeded 120 minutes (group 2). Groups were homogeneous for demographics, preoperative laboratory tests, background liver, and type of tumors. RESULTS: Operation length, and number of lesions removed, was significantly higher in group 2. Conversely, the two groups experienced similar amount of blood loss, rate of blood transfusions, overall and major morbidity, and 30- and 90-day postoperative mortality. In particular, in group 2 there was no mortality at all. Mean serum total bilirubin and alanine aminotransferase level on seventh pod resulted significantly higher in group 2, conversely mean aspartate aminotransferase, cholinesterases, and prothrombin time not differed in 2 groups. CONCLUSIONS: This study shows that hepatectomies done with intermittent clamping exceeding 120 minutes are as safe as those performed with shorter one despite more complex tumor presentations. This seems encouraging the diffusion of procedures done in 1 stage for extensive liver diseases despite the prolonged clamping time. PMID- 21975323 TI - Selective diaphragm muscle weakness after contractile inactivity during thoracic surgery. AB - RATIONALE: Postoperative pulmonary complications are significant contributors to morbidity in patients who have undergone upper abdominal, thoracic, or cardiac surgery. The pathophysiology of these complications might involve postoperative inspiratory muscle weakness. The nature of postoperative inspiratory muscle weakness is unknown. OBJECTIVE: To investigate the effect of surgery on the functioning of the diaphragm, the main muscle of inspiration. METHODS: Serial biopsies from the diaphragm and the latissimus dorsi muscle were obtained from 6 patients during thoracotomy for resection of a tumor in the right lung. Biopsies were taken as soon as the diaphragm had been exposed (t(0)) and again after 2 hours (t(2)). The contractile performance of demembranated muscle fibers, as well as fiber morphology and markers for proteolysis, was determined. RESULTS: In all patients, the force-generating capacity of diaphragm muscle fibers at t(2) was significantly reduced (~35%) compared with that at t(0), with a more pronounced force loss in type 2 fibers compared with type 1 fibers. Diaphragm weakness was not part of a generalized muscle weakness as contractile performance of latissimus dorsi fibers was preserved at t(2). Diaphragm fiber size and myofibrillar structure were not different at t(2) compared with t0, but myosin heavy chain type 2 was significantly reduced at t(2) and MuRF-1 mRNA and protein levels were elevated at t(2). CONCLUSIONS: Only 2 hours of thoracic surgery causes marked, and selective, diaphragm muscle fiber weakness. PMID- 21975324 TI - Ethnic variations in chest pain and angina in men and women: Scottish Ethnicity and Health Linkage Study of 4.65 million people. AB - BACKGROUND: European research on ethnic variations in cardiovascular disease has mostly examined mortality endpoints using country of birth as a proxy for ethnicity. We report on chest pain and angina by ethnic group. DESIGN AND METHODS: Retrospective cohort linking the Census 2001 for Scotland (providing 14 ethnic group categories) and hospital discharge/community and hospital deaths data. Directly age-standardized rates and rate ratios were calculated. Risk ratios were adjusted for age and then highest educational qualification of the individual using Poisson regression. Ratios were multiplied by 100 and 95% confidence intervals (CI) were calculated. The reference was the White Scottish population (100). In the results below, the 95% CI excludes 100. RESULTS: There was raised chest pain mortality/hospital discharge risk in Indian men (rate ratio 141.2), Other South Asian women (rate ratio 140.9), and Pakistanis (rate ratio 216.2 in men, 243.0 in women). Rate ratios were lowest in other White British (rate ratio 76.1 in men, 73.7 in women) and Chinese (rate ratio 67.6 in men, 76.7 in women). Adjustment for age and education attenuated, but did not abolish, differences in other White British (risk ratio from 73.5 to 83.5) and Pakistani (risk ratio from 209.0 to 198.2) male populations and increased them in most others, e.g. other South Asian men (from risk ratio of 128.9 to 140.1). Pakistani populations had the highest risk of angina (rate ratio 189.3 in men, 159.7 in women). Other White British (rate ratio 81.4 for men, 78.0 for women), Other White (rate ratio 89.6 men, 85.2 women), and Chinese (rate ratio 60.5 men, 67.4 women) had the lowest risk. Adjustment for education did not greatly alter these patterns. CONCLUSIONS: There were important ethnic variations. The results call for replication elsewhere in Europe and targeted prevention programmes and vigilant diagnosis and management by clinicians. PMID- 21975325 TI - Mechanism and release rates of surface confined cyclodextrin guests. AB - The dissociation of a cobalt bisdiphenylterpyridine, [Co(biptpy)(2)](2+), guest at mixed (gamma-CD-(py)(2))-alkanethiol layers (where gamma-CD-(py)(2) is di 6(A), 6(B)- deoxy-6-(4-pyridylmethyl)amino- gamma-cyclodextrin) formed on platinum electrodes is reported. Cyclic voltammetry (CV) shows reversible one electron surface confined waves consistent with the Co(2/3+) couple bound at the interface. The quantity of [Co(biptpy)(2)](3+) reduced is found to be dependent on the scan rate employed, with greater amounts at higher scan rates. This behavior is in contrast to the CD guest ferrocene, which upon oxidation to the ferrocenium ion shows little charge associated with reduction even at elevated scan rates. Chronocoulometry was conducted to systematically vary the time spent oxidizing [Co(biptpy)(2)](2+) and to measure the resulting charge associated with the reduction of [Co(biptpy)(2)](3+). It is determined experimentally that as the pulse width increases, i.e. greater time spent in the oxidizing region, the amount of charge needed to reduce [Co(biptpy)(2)](3+) decreases dramatically. This decrease, along with the CV data, suggests strongly that the [Co(biptpy)(2)](3+) dissociates from the cavity. Significantly, this dissociation of the interfacial host-guest complex occurs on a much longer timescale (the order of seconds) compared to the oxidation of [Co(biptpy)(2)](2+) to [Co(biptpy)(2)](3+), which has been measured using high speed chronoamperometry to occur with a rate contant, k(0), of approximately 10(3) s(-1). The comparison of the timescale for dissociation of the interfacial complex and for electron transfer signifies that the electron transfer step occurs before dissociation, i.e. dissociation via an EC mechanism. The dissociation mechanism of [Co(biptpy)(2)](3+) is contrasted with that of the ferrocene/ferrocenium couple. PMID- 21975326 TI - Primary choriocarcinoma of the renal pelvis presenting as intracerebral hemorrhage: a case report and review of the literature. AB - INTRODUCTION: A choriocarcinoma is a malignant neoplasm normally arising in the gestational trophoblast, gonads and, less frequently, the retroperitoneum, mediastinum and pineal gland. Primary choriocarcinomas of the renal pelvis are extremely rare. CASE PRESENTATION: We report a case of primary choriocarcinoma of the renal pelvis in a 38-year-old Greek woman of reproductive age, presenting with a sudden development of intracerebral hemorrhage due to metastatic lesions. The diagnosis was established with a renal biopsy, along with an elevated serum level of beta-human chorionic gonadotropin. An extensive diagnostic work up confirmed the origin of the choriocarcinoma to be the renal pelvis. CONCLUSION: Extragonadal choriocarcinomas are rare neoplasms that require extensive laboratory and imaging studies to exclude a gonadal origin. Moreover, this is the first case of severe intracerebral hemorrhage as the initial presentation of primary choriocarcinoma of the renal pelvis. Nonetheless, choriocarcinomas should be considered in the differential diagnosis of women of reproductive age. PMID- 21975327 TI - "Intra base off/inter base on" coordination: self-assembly of a dimeric vitamin B12 derivative with a versatile tail. AB - A self-complementary, artificial vitamin B12 derivative dimerises in an unprecedented "intra base off/inter base on" coordination mode. PMID- 21975328 TI - Principal signalling complexes in haematopoiesis: structural aspects and mimetic discovery. AB - Blood production is a highly regulated process involving multiple inhibitory and stimulatory cytokines present in the haematopoietic stem cell niche. Small molecules mimics of these signalling molecules have substantial potential as drugs and in the development of bioreactors to generate blood products. We review the structural biology of the extracellular signalling domains of five of the most important cytokines, analyze their structure-property relationships, and summarize the progress in developing small molecule mimics using the molecular information from structural biology and mutation studies. PMID- 21975329 TI - Or why translational research is vital for the future treatment of rectal cancer. PMID- 21975330 TI - MET and VEGF: synergistic targets in castration-resistant prostate cancer. AB - Recent advances in the treatment of prostate cancer have resulted in improved outcomes, including longer survival, but new options are needed for treating patients with castration-resistant disease, particularly in the presence of bone metastasis. Data from preclinical models and clinical biomarker studies indicate that antiangiogenic agents should be a promising treatment for this patient population, and multiple agents in this class have demonstrated activity in early stage clinical trials. Pivotal trials in prostate cancer with agents targeting vascular endothelial growth factor (VEGF) signalling have resulted in significant improvements in tumour response and progression-free survival. However, overall survival was not significantly improved. Recent preclinical studies suggest that the limited impact on overall survival may result from the development of evasive resistance after inhibition of angiogenesis, possibly through upregulation of MET (hepatocyte growth factor receptor) signalling. MET plays important roles in angiogenesis, tumour cell invasion and bone metastasis, all of which are key factors in castration-resistant prostate cancer. Inhibition of both the MET and VEGF pathways may improve the efficacy of angiogenesis inhibitors in prostate cancer. PMID- 21975331 TI - Targeted therapy with bevacizumab (Avastin) for metastatic colorectal cancer. AB - During the last decade, the development of new drugs known as targeted therapies was the result of a better understanding of the processes involved in the transformation of normal cells into cancer. The term targeted therapy refers to drugs that selectively target specific molecular pathways involved in tumorigenesis or tumour progression. Angiogenesis is important for tumour growth and metastasis, and is an important target for new biological agents. Bevacizumab is a humanised recombinant antibody that prevents vascular endothelial growth factor (VEGF) receptor binding, and inhibits angiogenesis and tumour growth. On February 26, 2004, the Food and Drug Administration approved bevacizumab as first line treatment for patients with metastatic colorectal cancer (CRC). The integration of targeted therapies in the treatment of colon cancer has resulted in significant improvements in efficacy outcomes. The efficacy of bevacizumab in the treatment of metastatic CRC is presented in this review article. PMID- 21975332 TI - Synchrotron radiation in cancer treatments and diagnostics: an overview. AB - During the last 30 years many groups have carried out experiments and trials to develop new imaging and radiotherapy techniques in oncology, based on the use of synchrotron X-rays. There are several synchrotron biomedical stations around the world, which offer an excellent platform to improve either the imaging diagnosis or radiotherapy treatment for different tumour types. In the coming months the first radiotherapy clinical trials will be seen at the Biomedical Beamline at the ESRF synchrotron in Grenoble (France). In this article we highlight the results of some of the techniques and strategies that have been developed at different biomedical synchrotron stations. PMID- 21975333 TI - Multidisciplinary approach of colorectal liver metastases. AB - Colorectal cancer (CRC) is the second most common cause of cancer death in Spain. Fifty percent of patients will develop colorectal liver metastases (CLM) during the course of the disease. Less than 20% of patients with CLM are initially resectable and for them 5-year disease-free survival (DFS) is about 20-25%, with a high recurrence rate. CLM is a heterogeneous disease. From a clinical point of view, four main groups can be differentiated: initially resectable, not optimally resectable, unresectable that could be resectable and unresectable that never will be likely to be resected. Treatment of CLM must be established, always, in a multidisciplinary team discussion with an analysis of prognostic factors and resectability. For patients with resectable CLM, the EORTC trial 364 demonstrated that chemotherapy plus surgery is better than surgery alone. Consequently most patients should be treated with perioperative chemotherapy based on oxaliplatin, and if resection has been done without chemotherapy, they should receive adjuvant chemotherapy after R0 resection. Based on oncological factors, the 5-year survival rate after resection of CLM ranges from 60% to only 14% with a poor score. If a patient has more than one of the poor prognostic factors he should probably be referred for preoperative (induction) chemotherapy. Only a minority of patients with CLM are amenable to surgery; therefore, efforts have been made to increase the percentage of patients who could be candidates for resection. Studies, mostly retrospective, have confirmed the ability of neoadjuvant chemotherapy (conversion chemotherapy) to render some metastases resectable. The regimens we must use depend on the KRAS mutational status and the toxicity profiles of drugs in the context of each patient. In k-ras mutated tumours we can use bevacizumab combined with standard chemotherapy or concomitant administration of the three active agents (FOLFOXIRI) in suitable patients. In k-ras wild-type patients, the combination of cetuximab and FOLFIRI-FOLFOX improved response rates and resection rate in phase III-II trials. With a lower level of evidence, panitumumab is an alternative combined with FOLFOX. Bevacizumab is also an alternative as it does not depend on KRAS status. Radiotherapy is becoming an alternative in selected patients, where surgery is not an alternative. For the majority of patients, who will never be resectable, the continuum of care with chemotherapy will be the paradigm for their management. PMID- 21975334 TI - Asthma and risk of lung cancer. AB - Asthma is a very common chronic disease that occurs in all age groups. Its high prevalence has significant health costs, which are even higher in the most severe disease forms. Lung cancer has the highest incidence of all cancers in the developed world and is an important cause of mortality. Patients with lung cancer are a big economic burden on health services, both in direct and indirect costs. Different authors suggest that atopic constitution, including different manifestations of allergy and asthma, are possible risk factors for lung cancer, above all in never-smokers. Given the high asthma prevalence and lung cancer incidence and mortality in developed countries, this association would have important public health implications. Uncertainties about the association and the underlying physiopathological mechanisms, however, seem to require further studies. PMID- 21975335 TI - Prognostic significance of biochemical markers in African Burkitt's lymphoma. AB - BACKGROUND AND PURPOSE Endemic Burkitt's lymphoma (eBL) remains the prevalent form of paediatric cancer in tropical Africa with subtle pathological differences. This calls for intensified efforts to validate the global prognostic markers within local settings for improved cancer treatment and survival. This study proposes prognostic markers for enhanced eBL treatment and management. PATIENTS AND METHOD One hundred and eighty histologically and/or clinically diagnosed BL patients at Komfo Anokye Teaching Hospital, Kumasi, Ghana were eligible for this cross-sectional eight-year retrospective study. Biochemical, clinical and demographic data, before chemotherapy administration, were documented and examined for their progression-free (PFS) and overall survival (OS) significance. RESULTS A mean age of 6 (SD=2.7, range: 1-16) years was observed with general male dominance (M:F=1.69:1). Total serum lactate dehydrogenase (HR=2.04; 95% CI, 1.25-3.32; log rank=8.3; p=0.004), serum creatinine (HR=3.59; 95% CI, 1.62-7.98; log rank=15.4; p=0.002) and St. Jude stage (HR=1.74; 95% CI, 1.11-2.73; log rank=8.0; p=0.015) were important independent prognostic biochemical markers for both PFS and OS. Age, serum calcium, uric acid, potassium, sodium and phosphorus were non-prognostic. CONCLUSION The better monitoring of these prognostic indices coupled with risk stratification treatment may improve patients' survival, especially in resource limited settings. PMID- 21975336 TI - Does gender matter in glioblastoma? AB - BACKGROUND The clinical outcome of glioblastoma (GBM) patients who receive radiotherapy alone or with chemotherapy is well established. However, little is known about how many patients do not receive this treatment. We consider it is important to investigate why a proportion of operated patients do not receive further treatment after surgery. METHODS We reviewed all consecutive GBM patients operated on in our hospital between January 2000 and December 2008. RESULTS A total of 216 patients with GBM were identified. Fifty-five (25%) did not receive any treatment after surgery. Univariate analysis showed that factors associated with no further treatment after surgery were older than 60 years (p=0.002), of female gender (p=0.03), had a KPS<70 (p<0.001) and had had a biopsy (p<0.001). Multivariate analysis indicated that age =60 years and KPS <70 were independent predictors of no further treatment after surgery. Gender was not an independent variable. However, women in the whole series were older than 60 years (p=0.01), and they had a worse KPS (p=0.02) and more biopsies (p=0.04) than men. In the whole group, median survival time was 10.4 months for men (n=125) vs. 7.2 months for women (n=91), log rank p<0.04. This difference was not observed in the group that was treated after surgery. CONCLUSIONS One out of four patients could not be treated after surgery. Independent predictors were older age and low KPS. These poor risk variables were more frequent in women and their survival was therefore lower than men in our series. PMID- 21975337 TI - A safety and toxicity assessment of the administration of multiple intracerebral injections of irinotecan or doxorubicin drug-eluting beads. AB - OBJECTIVE Previous research in a rat glioma model has shown that the local intratumoral application of polymerbased drug-eluting beads (DEBs) loaded with doxorubicin or irinotecan suppress tumour growth and prolong survival. For translation into a clinical setting, the present experiment investigates in the healthy cat brain the local and systemic toxicity of a multiple injection shot technique. METHODS Three injection shots were placed, each at a 1 cm distance in the frontal lobe. The DEBs were suspended in an aqueous alginate excipient solution, which becomes subject to a sol-gel transition when injected into the Ca(2+)- rich brain tissue environment. Systemic and local side effects were monitored over a period of two weeks. Injection sites were histologically investigated. RESULTS Gelling of the alginate results in the permanent immobilisation of the microspheres at the implantation site. A distinct local cytotoxic effect of doxorubicin was found with intracerebral and intraventricular haemorrhages, and signs of brain tissue necrosis. In cats injected with irinotecan DEBs, such local adverse side effects did not occur. No signs of systemic toxicity were found with both chemotherapeutics. DISCUSSION We conclude that the multiple injection shot technique with irinotecan DEBs meets feasibility criteria and safety requirements for a clinical application. PMID- 21975338 TI - Change of telomerase activity in peripheral whole blood of head and neck squamous cell carcinoma patients before and after surgery: a pilot study. AB - BACKGROUND The purpose of this study was to evaluate telomerase activity in peripheral whole blood from head and neck squamous cell carcinoma (HNSCC) patients as a biomarker for diagnosis of HNSCC or detection of recurrence during follow-up. MATERIALS AND METHODS Telomerase activity was measured from peripheral whole blood extracts by telomerase repeat amplification protocol (TRAP) in HNSCC patients before and after surgery and in a control group. Sixty-two HNSCC patients and 42 control subjects were included. RESULTS Telomerase activity was found in 41 out of 62 (66.1%) HNSCC patients before surgery and in 8 out of 42 (19.0%) controls (p<0.001). Among 41 HNSCC patients who showed positive telomerase activity before surgery, 32 (78.1%) showed a conversion of telomerase activity to negative after surgery. In follow-up, 6 out of 8 (75%) showed conversion of telomerase activity from negative to positive after recurrence. Telomerase activity was changed to negative in 4 out of 6 (66%) recurred patients with positive telomerase activity after second surgery. CONCLUSION The telomerase activity in peripheral whole blood extracts of HNSCC patients might be a useful biomarker for detecting recurrence after treatment. Further study with larger sample size using a more sensitive detection method of telomerase activity is necessary to verify these results. PMID- 21975340 TI - Prevention of acute radiation enteritis: efficacy and tolerance of glutamine. AB - PURPOSE Our primary endpoint is to determine the effect of L-glutamine Resource (Nestle Healthcare Nutrition) in the prevention of induced enteritis after pelvic radiotherapy (RT). METHODS We observed the incidence of diarrhoea during and after pelvic radiation therapy in patients receiving L-glutamine Resource (Nestle Healthcare Nutrition) supplementation. To assess results, patients were stratified according to prior treatment (prior surgery and/or concomitant chemotherapy, or no prior or concomitant treatment). RESULTS Incidence of diarrhoea observed is similar to published series in which glutamine is not administered. Grade 1 intestinal toxicity was observed in 4 patients (15.4%), grade 2 in 10 patients (38.4%) and grade 3 in 5 patients (19.2%). Mean dose of RT at the start of enteritis was 23.55 Gy (12-40). No grade 4 toxicity occurred and in 7 patients (27%) no toxicity was reported. No differences in toxicity incidence were observed between RT dose levels. CONCLUSIONS Administration of glutamine to patients during pelvic RT does not appear to prevent the incidence of enteritis (diarrhoea). No differences were observed between patients who underwent concomitant chemotherapy (where you would expect an increase in toxicity) and those who did not. PMID- 21975339 TI - Molecular changes consistent with increased proliferation and invasion are common in rectal cancer. AB - BACKGROUND Survival in rectal cancer remains unchanged despite improved treatment modalities. Molecular biology may hold the key to new strategies. Gene expression abnormalities need identification in tumour specimens to identify targets for therapy. The impact of neoadjuvant therapy on induced gene expression changes needs to be assessed to distinguish the intrinsic tumour-specific changes from those changes that may be induced by neoadjuvant therapy. METHODS Gene expression changes were examined in 21 rectal tumours plus matched normal mucosa and cells exposed to 5-FU and gamma radiation, using DNA membrane arrays. These arrays contained 100 genes in common cancer pathways. The most commonly up-regulated gene, c-FOS, was quantified using real-time PCR. RESULTS c-FOS was the most commonly up-regulated gene, occurring in 7 of 21 samples (33%), all samples having a greater than 2-fold increase. SERPINE-1 was the second most commonly up regulated gene with 6 of 21 samples showing up-regulation (29%). There was no clear correlation between up-regulation of c-FOS or SERPINE-1 and clinico pathological data. Neither c-FOS nor SERPINE-1 gene expression was induced by 5 FU treatment or gamma irradiation in vitro, but MUC 18 was up-regulated by 5-FU treatment. This suggests that FOS and SERPINE-1 expression changes are specific to the tumour and will not arise as artefacts of neoadjuvant therapy. CONCLUSION The study suggests that c-FOS and SERPINE-1 may have important but as yet unclear roles in the tumour biology of rectal cancer but probably only represent a small part of the complex molecular biology of rectal cancer. PMID- 21975341 TI - A versatile and highly sensitive probe for Hg(II), Pb(II) and Cd(II) detection individually and totally in water samples. AB - The detection of heavy metal ions using enzyme-linked immunosorbent assays (ELISA) has been reported by several research groups. However, highly sensitive and selective detection of total heavy metal ions using ELISA is a major technical limitation. Here we describe the development of a versatile and highly sensitive probe combining goat anti-mice IgG, colloidal gold nanoparticles (AuNPs) and horseradish peroxidase (HRP). We demonstrate the utility of this probe using three kinds of heavy metal complete antigens and three monoclonal antibodies (McAbs) in one ELISA system to establish a high-throughput screening protocol. The procedure was successfully applied to analysis of Hg(II), Pb(II) and Cd(II) individually and totally from different water samples. The sensitivities for the detection of Hg(II), Pb(II) and Cd(II) individually and totally are 27.4, 3.9, 15.8 and 18.2 nM, respectively. And all limit of detection (LODs) are lower than 1.2 nM. The recovery results obtained from the developed technique showed a good correlation (R(2)=0.983) with those from ICP-MS. The major advantage of the probe is the versatility and high sensibility. The probe could be potentially used, upon demand, as a sensitive and versatile detector for a broad range of applications. PMID- 21975342 TI - Hyponatremia in hospitalized nursing home residents and outcome: minimize hospitalization and keep the stay short! PMID- 21975343 TI - Dementia-related agitation. PMID- 21975344 TI - Current dilemmas of nursing homes in Chengdu: a cross-sectional survey. AB - OBJECTIVES: Chengdu, China, is facing challenges from the growth of the elderly population. There are nursing homes in Chengdu, but there is no study on the current status of these nursing homes and their residents. The present study was conducted to investigate the current situation of nursing homes in Chengdu. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study randomly selected 10 nursing agencies from the 110 agencies in Chengdu (5 main zones and districts) using a cluster random sampling method. Descriptive statistics were used to analyze the data. RESULTS: Ten agencies (10%) were surveyed: 5 government-run social welfare, 2 collective run, and 3 private institutions. The basic service in the nursing home includes personal care, basic medical care, room cleaning, meals, and laundry. Standard setting, assessment, rehabilitation therapy, and some equipment and volunteer service monitoring are inadequate. Most care staff receive little training in elder care. Some have no qualified certification and they have low income, heavy work, and insufficient knowledge. The whole team has a high mobility. CONCLUSIONS: Nursing homes in Chengdu are at a lower level than those in developed countries. PMID- 21975345 TI - Developing a valid patient-reported outcome measure. PMID- 21975346 TI - Mechanisms involved in placebo and nocebo responses and implications for drug trials. PMID- 21975347 TI - Acetaminophen metabolism after major surgery: a greater challenge with increasing age. AB - Patients undergoing major surgery represent a good model for the study of the hepatic metabolism of acetaminophen (APAP) after surgery and for the evaluation of how the detoxification process is influenced by aging. Thirty patients received intravenous APAP (1 g/6 h) for 4 days (D1-D4). Daily 24-h urinary metabolites-cysteine-APAP, mercapturate-APAP, APAP, and glucuronide and sulfate conjugates-as well as blood glutathione levels were compared with repeated measures analysis of variance (significance, P<0.05). Between D1 and D4, cysteine APAP increased (308+/-308 mg vs. 570+/-512 mg, P=0.005), and sulfate and glucuronide conjugates decreased (1,365+/-1,084 mg vs. 694+/-600 mg, P<0.0001 and 2,418+/-817 mg vs. 1,513+/-1,076 mg, P=0.011, respectively). Blood glutathione decreased (790+/-125 vs. 623+/-132 umol/l, P<0.0001. These changes increased with aging. APAP disposition after major surgery shifts toward the oxidative pathways of metabolism, and this is enhanced with aging. Supplementation with sulfur containing amino acids should be investigated further as it might minimize the effect on antioxidant defenses, especially in older persons undergoing more extensive surgical procedures. PMID- 21975348 TI - Pharmacokinetics, pharmacodynamics, safety, and tolerability of JNJ-38431055, a novel GPR119 receptor agonist and potential antidiabetes agent, in healthy male subjects. AB - The incidence of type 2 diabetes mellitus is increasing worldwide. Several G protein-coupled receptor agonists are being studied for their efficacy as antidiabetes agents. JNJ-38431055 is a novel, potent, and orally available selective agonist of the glucose-dependent insulinotropic (GPR119) receptor. Double-blind, randomized, placebo-controlled studies were conducted to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of JNJ-38431055 (2.5-800 mg) in healthy male volunteers. The systemic exposure of JNJ-38431055 in plasma increased in proportion to the dose and was not influenced by coadministration of food. The terminal elimination half-life was ~13 h when administered as an oral suspension formulation. JNJ-38431055 was well tolerated and was not associated with hypoglycemia. As compared with placebo, single-dose oral JNJ-38431055 increased postmeal plasma glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and peptide YY (PYY) concentrations but did not significantly decrease glucose excursion or increase insulin secretion. However, in a graded glucose infusion study, JNJ 38431055 was shown to induce a higher insulin secretion rate (ISR) relative to placebo at elevated plasma glucose levels. These studies provide evidence for the potential efficacy of JNJ-38431055 as an antidiabetes agent in humans. PMID- 21975349 TI - Linking pharmacology to clinical reports: cyclobenzaprine and its possible association with serotonin syndrome. AB - The link between cyclobenzaprine (Flexeril) administration and serotonin syndrome (SS) is subject to debate. Establishing such a connection is difficult because of the limited number of case reports available and the almost complete ignorance of its preclinical pharmacology. In this context, evidence is provided here that cyclobenzaprine blocks the serotonin and norepinephrine transporters and binds to another set of five serotonin receptors. SS should be considered when indicative signs occur in the context of cyclobenzaprine use. PMID- 21975351 TI - Theoretical and numerical calculation of the acoustic radiation force acting on a circular rigid cylinder near a flat wall in a standing wave excitation in an ideal fluid. AB - The acoustic radiation force acting on a cylinder near a flat wall in a standing wave is calculated by analytical methods and numerical simulations. An exact theoretical solution is presented as well as an approximate solution. The approximate solution is in algebraic form and quite easy to compute. The numerical simulation is based on FVM (Finite Volume Method) on unstructured triangular meshes. The exact theoretical, approximate and numerical solutions are compared with each other and good agreements are obtained. Furthermore, the effects of the flat wall are investigated in detail by the three methods. PMID- 21975352 TI - Incidence of impaired renal function after lung transplantation. AB - BACKGROUND: Impaired renal function is a frequent complication after lung transplantation (LTx). Since the early days of LTx, recipient eligibility criteria slowly became less strict, while treatment regimens evolved. These developments may have had opposing effects on the risk for impaired renal function. We aimed to study changes in recipient characteristics in conjunction with incidence of impaired renal function in consecutive series of lung transplant recipients (LTRs). METHODS: Three hundred forty adult LTRs (mean age 45 +/- 12 years, 50.3% male, median follow-up 3.4 [1.0 to 7.1] years) were divided into four consecutive patient time-series: 1990 to 1996 (n = 93); 1997 to 2001 (n = 79); 2002 to 2005 (n = 89); and 2006 to 2008 (n = 79). The primary end point was cumulative incidence of doubling of serum creatinine (DSC), taking into account the competing risk of death. Measured glomerular filtration rate (mGFR; (125)I-Iothalamate) was assessed as a secondary end-point. RESULTS: Mean age at transplantation (p = 0.001), prevalence of hypertension (p = 0.005), pack-years of former smoking (p = 0.001) and body mass index (p = 0.05) increased across the consecutive series. The cumulative incidence of DSC at 24 months after LTx was 43%, 37%, 35% and 29%, respectively, in the consecutive series (p = 0.01). Despite higher prevalence of renal risk factors, there was lower adjusted risk of DSC in the consecutive series, with hazard ratios [95% CI] of 0.62 [0.34 to 1.15], 0.50 [0.25 to 0.98] and 0.31 [0.154 to 0.67], respectively, compared with the 1990 to 1996 series. Accordingly, mGFRs at 24 months after LTx were 51 +/- 17, 53 +/- 17, 57 +/- 21 and 63 +/- 21 ml/min/1.73 m(2) in the consecutive series (p = 0.002). CONCLUSIONS: Despite the higher prevalence of renal risk factors in more recently transplanted patients, renal outcome after LTx has improved over time. Nevertheless, impaired renal function remains a frequent complication after LTx. PMID- 21975350 TI - Plasma letrozole concentrations in postmenopausal women with breast cancer are associated with CYP2A6 genetic variants, body mass index, and age. AB - The associations between plasma letrozole concentrations and CYP2A6 and CYP3A5 genetic variants were tested in the Exemestane and Letrozole Pharmacogenomics (ELPH) trial. ELPH is a multicenter, open-label prospective clinical trial in women randomly assigned (n~250 in each arm) to receive 2 years of treatment with either oral letrozole (2.5 mg/day) or oral exemestane (25 mg/day). CYP2A6 and CYP3A showed effects on letrozole metabolism in vitro. DNA samples were genotyped for variants in the CYP2A6 and CYP3A5 genes. Plasma letrozole concentrations showed high interpatient variability (>10-fold) and were associated significantly with CYP2A6 genotypes (P<0.0001), body mass index (BMI) (P<0.0001), and age (P=0.0035). However, CYP3A5 genotypes showed no association with plasma letrozole concentrations. These data suggest that CYP2A6 is the principal clearance mechanism for letrozole in vivo. CYP2A6 metabolic status, along with BMI and age, may serve as a biomarker of the efficacy of letrozole treatment or a predictor of adverse effects. PMID- 21975353 TI - Prehension synergy: use of mechanical advantage during multifinger torque production on mechanically fixed and free objects. AB - The aim of this study was to test the mechanical advantage (MA) hypothesis in multifinger torque production tasks in humans: fingers with longer moment arms produce greater force magnitudes during torque production tasks. There were eight experimental conditions: two prehension types determined by different mechanical constraints (i.e., fixed- and free-object prehension) with two torque directions (supination and pronation) and two torque magnitudes (0.24 and 0.48 N.m). The subjects were asked to produce prescribed torques during the fixed-object prehension or to maintain constant position of the free hand-held object against external torques. The index of MA was calculated for agonist and antagonist fingers, which produce torques in the same and opposite directions to the target torques, respectively. Within agonist fingers, the fingers with longer moment arms produced greater grasping forces while within antagonist fingers, the fingers with shorter moment arms produced greater forces. The MA index was greater in the fixed-object condition as compared with the free-object condition. The MA index was greater in the pronation condition than in the supination condition. This study supports the idea that the CNS utilizes the MA of agonist fingers, but not of antagonist fingers, during torque production in both fixed- and free-object conditions. PMID- 21975354 TI - Exercise blood pressure response is related to asymmetric dimethylarginine and osteoprotegerin in hypertension. PMID- 21975355 TI - Predictors of myocardial microvascular obstruction in patients treated by primary percutaneous coronary intervention and a short ischemic time. PMID- 21975356 TI - Current treatment strategies, complications and considerations for the use of HIV antiretroviral therapy during pregnancy. AB - The global prevalence of HIV infection in the female population presents a significant healthcare burden in terms of mother-to-child transmission (MTCT) of the disease. This review aims to discuss current trends and treatment guidelines for the use of antiretroviral therapy during pregnancy and associated complications in this population. Historically, antiretroviral monotherapy with zidovudine was commonly used for preventing MTCT, and monotherapy with single dose nevirapine is still used for prevention in resource-limited settings. Evidence suggests that combination therapy with HAART is a more effective treatment option than monotherapy when managing HIV in pregnant women. Current treatment guidelines recommend the use of HAART with a protease inhibitor (PI) or a nonnucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside reverse transcriptase inhibitors (NRTI) as first-line therapy for the management of HIV infection in pregnant women and for preventing MTCT. Complications associated with the use of antiretroviral therapy during pregnancy should be taken into consideration when selecting a new antiretroviral regimen, or when continuing certain antiretroviral regimens in HIV-infected women who become pregnant while on therapy. NNRTI have been associated with severe and sometimes fatal hepatoxicity in some pregnant women and potentially teratogenic side effects in the fetus, and their use raises concerns regarding the development of drug- and class-resistant mutations. PI-based HAART has been associated with an increased risk of adverse effects such as premature delivery, low birth weight, dyslipidemia, glucose intolerance, and lipodystrophy. Despite this, initiating antiretroviral therapy with a PI plus two NRTI may become the preferred treatment option in pregnant women. Many of the side effects associated with PI were more prevalent when older PI and PI-based regimens that included those in combination with thymidine analog NRTI were used. An individual's history and baseline clinical and laboratory parameters should also be taken into consideration when choosing the most appropriate antiretroviral regimen during pregnancy. PMID- 21975357 TI - HIV drug resistance assessment in the Western Pacific region. A systematic review. AB - Antiretroviral therapy is being rapidly scaled-up in Western Pacific region countries. Prevention and assessment of HIV drug resistance is an essential component of successful global antiretroviral therapy scale-up. We performed a systematic review of public health surveys and HIV drug resistance studies conducted in the low- and middle-income countries in the Western Pacific region. A total of 38 publications assessing HIV drug resistance were reviewed. Studies assessing transmitted drug resistance in recently infected individuals or drug resistance among individuals starting antiretroviral therapy found low rates of HIV drug resistance. Assessments of HIV drug resistance emerging in populations receiving antiretroviral therapy demonstrated variable rates of drug resistance, but suggest an urgent need to support antiretroviral therapy adherence and retention in care, ensure the use of quality assured drugs, and guarantee continuous drug supplies. Additionally, programmatic assessment informed by routine standardized surveillance of transmitted and acquired HIV drug resistance is essential to optimize antiretroviral therapy delivery in the Western Pacific region. PMID- 21975358 TI - Protease inhibitors as preferred initial regimen for antiretroviral-naive HIV patients. AB - At present, the majority of patients who have initiated their first antiretroviral therapy have received a combination comprising a nonnucleoside and two nucleoside analogues. The use of nonnucleosides as first-line therapy has been favored for their more convenient dosing, with less pill numbers, and the possibility of co-formulation with nucleoside analogues. Although protease inhibitors are also considered to be a preferred standard, they have been less frequently used as first regimen of choice because of their adverse effects in the short to medium term. The introduction of darunavir and atazanavir as new protease inhibitors boosted with ritonavir has resulted in a significant change in this area. These drugs show a lower incidence of adverse effects, allow once-a day administration, and have a high barrier to resistance that prevents the selection of resistance mutations in case of virologic failure. On this basis, it is likely that over the next few years these drugs will become a standard of care, gaining acceptance and being used more frequently as preferred first-line regimen. PMID- 21975359 TI - Evolutionary mechanisms of retroviral persistence. AB - Retroviruses are known to exhibit remarkable genomic pliancy, a capacity that has been attributed to one or more error prone steps in the viral replication cycle. However, increasing evidence suggests that such error represents a key element in viral survival, as exemplified by studies on virus immune evasion, shifts of cellular tropism, and anatomic compartmentalization, which facilitate persistent virus reservoirs. Understanding the dynamic mechanisms that contribute to the establishment and maintenance of retroviral persistence is critical toward the goal of attaining HIV-1 eradication. PMID- 21975360 TI - Bone turnover markers in HIV disease. AB - Biomarkers are being increasingly used in basic and clinical research of HIV disease as well as clinical management of infected individuals. Bone metabolism can be assessed by measurement of bone turnover markers, molecules released during bone formation and removal of old bone (resorption). In HIV-infected adults, there is a higher prevalence of low bone mineral density and fractures compared to the general population. This review discusses the findings regarding bone turnover markers in HIV-uninfected and -infected populations and their potential role in assessing fracture risk and predicting bone loss. Studies in postmenopausal women and elderly men show that increased bone turnover markers levels are associated with bone loss, and high levels of resorption markers may predict fractures independently of bone mineral density. Several HIV-related factors, including HIV infection and inflammation, have been found to affect the balance between bone formation and resorption. Some clinical studies found increased levels of bone turnover markers in HIV-infected adults compared to uninfected controls. Furthermore, bone turnover marker levels increased following initiation or switch to different antiretroviral agents in recent randomized trials. The clinical value of bone turnover markers is currently limited due to different sources of variability and limited data from studies in HIV-infected populations. Further research is needed to explore the potential value of bone turnover markers as additional measurements to bone mineral density in fracture risk assessment and monitoring treatment-induced bone effects in HIV-infected patients. PMID- 21975362 TI - Widowhood, illegitimacy, marital reproduction and female longevity in a rural Spanish population. AB - Using data from parish and civil registers in a rural community in northwest Spain (Los Nogales), family reconstitution provided 1502 complete reproductive histories, of which 584 corresponded to first marriages of women dying after their 50th birthday. A homogeneous sample consisting of women married in the period 1877-1899 (N=311) provided information concerning their reproductive performance, including ages at first and last maternity and number of children born alive and surviving, which was related to the mother's post-menopausal longevity, also considering premarital fertility and her marital status (widow/married). The results obtained indicate that mothers with a lower proportion of children dying before the first birthday and the age of 15 (mainly males) have a greater post-reproductive longevity. Moreover, women with a more protracted end to their reproductive period and greater fertility live for more years beyond their 50th birthday. These results do not prove a causality between maternal longevity and more successful reproduction; instead, they are indicative of a holistic condition of health. A wide spectrum of favorable biological and environmental factors will have positive consequences for a woman's life trajectory, affecting both her reproductive performance and her own likelihood of surviving. PMID- 21975363 TI - Nonmetric tooth crown traits in a Sri Lankan aboriginal Vedda population. AB - This study was conducted to determine the frequencies of non-metric tooth crown traits of Vedda of Sri Lanka and to investigate the affinities of these morphological variations with those of other world populations. Fifty dental plaster casts were observed. The Arizona State University dental anthropology system was adopted for classification of the 16 traits observed. We used 13 traits to compare the Vedda and other world populations. Using the frequencies of 13 traits, Smith Mean Measure of Divergence was calculated to determine inter population distances. Affinities among the Vedda and other world populations were expressed in two dimensions of the principal coordinate analysis. Cusp number in mandibular second molar and hypocone absence in maxillary second molar had the highest frequency at 95.9% and 93.8%, respectively. Shovelling, double shovelling in the maxillary central incisor and deflecting wrinkle in the mandibular first molar had the lowest frequency at 0%. The principal coordinate analysis showed that Sino American and Western Eurasian populations were separated in negative and positive directions in the first principal coordinate axis. Vedda located with the Western Eurasian population groups. Sahul and Sunda Pacific populations located in the intermediate position between Sino American and Western Eurasian populations. The dental phenotype of Vedda has close affinities with those of early south Asian populations. They are far different from Sino American and Sunda pacific populations. Vedda shows closer affinities to Sahul Pacific and South African (Bantu) populations. PMID- 21975364 TI - Towards a system-paced near-infrared spectroscopy brain-computer interface: differentiating prefrontal activity due to mental arithmetic and mental singing from the no-control state. AB - Near-infrared spectroscopy (NIRS) has recently been investigated as a non invasive brain-computer interface (BCI) for individuals with severe motor impairments. For the most part, previous research has investigated the development of NIRS-BCIs operating under synchronous control paradigms, which require the user to exert conscious control over their mental activity whenever the system is vigilant. Though functional, this is mentally demanding and an unnatural way to communicate. An attractive alternative to the synchronous control paradigm is system-paced control, in which users are required to consciously modify their brain activity only when they wish to affect the BCI output, and can remain in a more natural, 'no-control' state at all other times. In this study, we investigated the feasibility of a system-paced NIRS-BCI with one intentional control (IC) state corresponding to the performance of either mental arithmetic or mental singing. In particular, this involved determining if these tasks could be distinguished, individually, from the unconstrained 'no control' state. Deploying a dual-wavelength frequency domain near-infrared spectrometer, we interrogated nine sites around the frontopolar locations (International 10-20 System) while eight able-bodied adults performed mental arithmetic and mental singing to answer multiple-choice questions within a system paced paradigm. With a linear classifier trained on a six-dimensional feature set, an overall classification accuracy of 71.2% across participants was achieved for the mental arithmetic versus no-control classification problem. While the mental singing versus no-control classification was less successful across participants (62.7% on average), four participants did attain accuracies well in excess of chance, three of which were above 70%. Analyses were performed offline. Collectively, these results are encouraging, and demonstrate the potential of a system-paced NIRS-BCI with one IC state corresponding to either mental arithmetic or mental singing. PMID- 21975365 TI - More than mothers: aligning indicators with women's lives. PMID- 21975366 TI - Lyotropic liquid crystal engineering-ordered nanostructured small molecule amphiphile self-assembly materials by design. AB - Future nanoscale soft matter design will be guided to a large extent by the teachings of amphiphile (lipid or surfactant) self-assembly. Ordered nanostructured lyotropic liquid crystalline mesophases may form in select mixtures of amphiphile and solvent. To reproducibly engineer the low energy amphiphile self-assembly of materials for the future, we must first learn the design principles. In this critical review we discuss the evolution of these design rules and in particular discuss recent key findings regarding (i) what drives amphiphile self-assembly, (ii) what governs the self-assembly structures that are formed, and (iii) how can amphiphile self-assembly materials be used to enhance product formulations, including drug delivery vehicles, medical imaging contrast agents, and integral membrane protein crystallisation media. We focus upon the generation of 'dilutable' lyotropic liquid crystal phases with two- and three-dimensional geometries from amphiphilic small molecules (225 references). PMID- 21975367 TI - A simple ultrasound score for the identification of candidates to fine needle aspiration of thyroid nodules. AB - BACKGROUND: Cytological examination of fine needle aspirates (FNA) is the standard procedure for discriminating potentially malignant thyroid nodules to be referred to surgery. In a fraction of cases, ultrasound (US) examination could provide information theoretically sufficient to avoid FNA, when typical US features suggesting malignancies are lacking. AIM: The aim of this study was to construct a simple US score predicting malignant nodules so as to reduce the number of unnecessary FNA. SUBJECTS AND METHODS: In a series of 1632 consecutive patients undergoing US-guided FNA (1812 nodules), echostructure, echogenicity, margins, halo, microcalcification, and vascularization were assessed. RESULTS: At multivariate analysis, the following parameters showed a strong predictive value for positive cytology (Thy 4 and Thy 5, suspicious and diagnostic for malignancy, respectively, according to the Thyroid British Association): solid echostructure, irregular margins and hypoechogenicity [adjusted odd ratio (OR) 5.13 (1.58 16.66), 3.03 (1.70-5.39), 2.05 (1.17-3.57), respectively]. A 10-point Thyroid Risk Ultrasound Score (TRUS) was constructed on the basis of the adjusted OR. A TRUS>=6 identified malignant nodules with sensitivity and specificity of 73% and 65%, respectively. Among the patients with follicular lesions (Thy 3) and final diagnosis of carcinoma, about 65% had a TRUS>=6.0. CONCLUSIONS: The sensitivity of TRUS, although higher than that of other scores, could still be insufficient for the identification of patients who could avoid FNA in routine clinical practice, whereas its predictive value for Thy 3 lesions deserves further investigations. PMID- 21975368 TI - Graphene and graphene-based nanomaterials: the promising materials for bright future of electroanalytical chemistry. AB - Similar to its popular older cousins of fullerene and carbon nanotubes (CNTs), the latest form of nanocarbon, graphene, is inspiring intensive research efforts in its own right. As an atomically thin layer of sp(2)-hybridized carbon, graphene possesses spectacular electronic, optical, magnetic, thermal and mechanical properties, which make it an exciting material in a variety of important applications. In this review, we present the current advances in the field of graphene electroanalytical chemistry, including the modern methods of graphene production, and graphene functionalization. Electrochemical (bio) sensing developments using graphene and graphene-based materials are summarized in more detail, and we also speculate on their future and discuss potential progress for their applications in electroanalytical chemistry. PMID- 21975369 TI - Integrating informatics into the BSN curriculum: a review of the literature. AB - Even though health informatics (HI) education is an essential component of the undergraduate nursing curriculum, it remains controversial with no clear consensus on which knowledge and skills should be integrated in a baccalaureate nursing program. The purpose of this review article is to integrate literature on HI education in the nursing curriculum by examining previous and current literature on this topic, synthesizing the findings, and recommending guidelines and future directions for nurse educators. The computerized databases of CINAHL, MEDLINE, ERIC, Academic Search Premier, and Google Scholar were used to generate relevant literature. Nineteen studies published between 2000 and 2010 on HI education were included in this review, and from the critical and synthesis of those reports emerged four overarching themes: (a) lack of consensus on HI education; (b) impact on patient care outcomes; (c) faculty development through organizational collaboration; and (d) global disparities in HI education. Implications for nursing education and patient outcomes in clinical practice are also discussed. Further studies are warranted to promote the understanding and awareness of HI education in undergraduate nursing curriculum. PMID- 21975370 TI - Guillain-Barre syndrome after tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine: a case report. AB - INTRODUCTION: The association of Guillain-Barre syndrome with vaccination has been described in the literature; it is infrequent and controversial. An association with swine influenza, influenza, hepatitis and tetanus vaccination has been documented in few case reports. CASE PRESENTATION: A 40-year-old Caucasian man sustained a small right temporal epidural hematoma and nondisplaced right skull fractures after a fall from a roof. He was managed conservatively; a tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine was administered and a week later he was discharged home. A few days after his discharge, he experienced weakness and numbness in his legs, which progressed to involve his arms. Three weeks after his initial fall, he was readmitted with quadriparesis. A lumbar puncture revealed a cerebrospinal fluid protein of 790 mg/dL and one white blood cell. We diagnosed Guillain-Barre syndrome. Our patient was treated with intravenous immunoglobulin. Three months later his muscle strength had improved, but he continued to have tingling in his hands and feet and used a walker intermittently. CONCLUSION: To the best of our knowledge, this is the first case of Guillain-Barre syndrome to be reported in the English literature after administration of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine. PMID- 21975371 TI - A membrane-less enzymatic fuel cell with layer-by-layer assembly of redox polymer and enzyme over graphite electrodes. AB - Layer-by-layer (LBL) assembly of alternate osmium redox polymers and glucose oxidase, at anode, and laccase, at cathode, using graphite electrodes form a membrane-less glucose/O(2) enzymatic fuel cell providing a power density of 103 MUW cm(-2) at pH 5.5. PMID- 21975372 TI - Effects of vertical loading on arch characteristics and intersegmental foot motions. AB - The medial longitudinal arch plays a major role in determining lower extremity kinematics. Thus, it is necessary to understand the dynamics of the arch structure in response to load. The purpose of this study was to examine arch function in high- and low-arched feet during a vertical loading condition. Ten high- and ten low-arched females performed five trials in a sit-to-stand exercise. Ground reaction force (1200 Hz) and three-dimensional kinematics (240 Hz) were collected simultaneously. The high-and low-arched athletes had no differences in vertical deformation of the arch. High-arched participants were less everted than the low-arched athletes; furthermore, the high-arched athletes had smaller mid-forefoot eversion excursions. Differences between the high-arched and low-arched athletes occur through and motion at the mid-forefoot joint. PMID- 21975373 TI - Rac1 activation comes full circle. PMID- 21975374 TI - G4 DNA: at risk in the genome. PMID- 21975375 TI - Von Willebrand factor folds into a bouquet. PMID- 21975376 TI - Engineering MIL-53(Al) flexibility by controlling amino tags. AB - The flexibility of MIL-53(Al) can be tuned by adjusting the ratio of terephthalate and 2-amino terephthalate linkers incorporated into the framework during hydrothermal synthesis. PMID- 21975380 TI - Method development and validation of the simultaneous determination of a novel topoisomerase 1 inhibitor, the prodrug, and the active metabolite in human plasma using column-switching LC-MS/MS, and its application in a clinical trial. AB - A robust and sensitive method using liquid chromatography-tandem mass spectrometry was developed and validated for the simultaneous determination of a novel topoisomerase 1 inhibitor CH0793076 (3076), the prodrug CH4556300 (TP300), and the active metabolite CH0793011 (3011) in human plasma. All plasma analyzed with this method was acidified with 1M HCl and 46% citric acid solution in a ratio of 100:10:1 (v:v:v) to avoid the pH-based degradation of TP300 and to shift the equilibria of 3076 and 3011 between the lactone and carboxylate forms towards the lactone forms. After the plasma proteins were precipitated with methanol:acetonitrile:HCl 1M (50:50:1, v:v:v) containing stable isotopic internal standards, the analytes were trapped on an Xterra MS C18 column (10*2.1 mm i.d., 5 MUm) and separated on a Gemini C18 column (50*2.0 mm i.d., 5 MUm) using column switching liquid chromatography. Electrospray ionization in the positive-ion mode and multiple reaction monitoring were used to quantify the analytes with transitions m/z 587.2>441.2 for TP300, 459.1>415.2 for 3076, and 475.1>361.1 for 3011. The inter- and intra-day precisions were below 12%, and the accuracy was between -16% and 16% at the lower limit of quantitation (LLOQ) and between -11% and 14% at the other quality controls. The LLOQs of TP300, 3076, and 3011 were 0.8, 0.04, and 0.04 ng/mL, respectively. The validated method was successfully applied to clinical sample analysis and incurred sample reanalysis was also conducted. PMID- 21975377 TI - Vitamin D receptor gene polymorphisms and sex steroid secretion in girls with precocious pubarche in Southern Brazil: a pilot study. AB - BACKGROUND: Evidence suggests that precocious pubarche (PP) girls may have higher risk of developing polycystic ovary syndrome (PCOS) at later ages. Vitamin D receptor (VDR) gene polymorphisms have been implicated in the risk of diabetes and PCOS, but little is known about the role of VDR in PP. AIM: To assess the frequencies of VDR gene ApaI, TaqI, BsmI, and FokI polymorphisms and to determine whether these variants are associated with sex hormone concentrations in patients with PP and controls from southern Brazil. SUBJECTS AND METHODS: Blood was collected from 36 girls with PP and 197 controls for genotyping of BsmI and FokI polymorphisms using real-time PCR and of ApaI e TaqI polymorphisms using restriction fragment length polymorphism. Hormone levels were also determined. RESULTS: Genotype GG of the ApaI single nucleotide polymorphism (SNP) was more frequent in PP (30.6%) than in controls (16.2%) [odds ratio (OR): 2.269; confidence interval 95% (95%CI): 1.015-5.076; p=0.042]. This genotype was also associated with lower estradiol [35.30 (14.80-50.48) pg/ml vs 12.22 (6.49-23.69) pg/ml; p=0.025] and total testosterone levels (0.52 (0.39-0.84) ng/ml vs 0.20 (0.11-0.47) ng/ml; p=0.005) as compared with the TT + TG genotypes in girls with PP. The distribution of TaqI, BsmI, and Fokl SNP was similar in PP and controls, and no association was found between these polymorphisms and sex steroid levels. CONCLUSIONS: The ApaI SNP of the VDR gene was associated with PP in the studied population and may modulate ovarian steroid secretion in these girls. PMID- 21975381 TI - Simulation study of poled low-water ionomers with different architectures. AB - The role of the ionomer architecture in the formation of ordered structures in poled membranes is investigated by molecular dynamics computer simulations. It is shown that the length of the sidechain L(s) controls both the areal density of cylindrical aggregates N(c) and the diameter of these cylinders in the poled membrane. The backbone segment length L(b) tunes the average diameter D(s) of cylindrical clusters and the average number of sulfonates N(s) in each cluster. A simple empirical formula is noted for the dependence of the number density of induced rod-like aggregates on the sidechain length L(s) within the parameter range considered in this study. PMID- 21975382 TI - Potential role of FDG PET imaging in predicting metastatic potential and assessment of therapeutic response to neoadjuvant chemotherapy in Ewing sarcoma family of tumors. AB - AIMS AND OBJECTIVES: The aim of this study was to retrospectively correlate FDG uptake in primary Ewing sarcoma family of tumors (ESFT) with tumor behavior, and to evaluate whether FDG PET can be used to predict response to neoadjuvant chemotherapy (NACT) in this patient group. METHODS: Out of the total 54 patients of recently diagnosed ESFT who underwent pretreatment FDG PET imaging, group I included patients without metastasis at presentation (n = 34) and group II included those with metastasis at presentation (n = 20). Fourteen of these patients had undergone FDG PET after 4 cycles of induction chemotherapy and surgical resection of primary tumor. In this subgroup of 14 patients, maximum standardized uptake value (SUVmax) of primary tumor was estimated before and after 4 cycles of induction chemotherapy and was correlated with the histopathological response in terms of necrosis in the tumor specimen. RESULTS: Mean SUVmax in the primary tumor in group I patients was 6.84 and in group II patients, it was 11.31. The difference between mean SUVmax of these 2 groups was significant by Wilcoxon test analysis, with P < 0.01. In group II patients, SUVmax in metastasis with maximum FDG uptake was consistently lower as compared with that of primary tumor. In subgroup of 14 patients, Pearson correlation analysis showed that percentage change in SUVmax of primary tumor correlated well with percentage necrosis on histopathological examination (P < 0.01). CONCLUSION: FDG uptake in primary ESFT reflected its metastatic potential and hence the aggressive behavior. The significant correlation between change in metabolic activity of the primary tumor and histopathological response after neoadjuvant chemotherapy suggests that FDG PET may be an ideal noninvasive method to assess tumor behavior and response to therapy in ESFT. PMID- 21975383 TI - Comparison of MRI, F-18 FDG, and 11C-choline PET/CT for their potentials in differentiating brain tumor recurrence from brain tumor necrosis following radiotherapy. AB - OBJECTIVE: To compare potentials of magnetic resonance imaging (MRI), F-18 FDG, and 11C-Choline PET/CT in differentiating brain tumor recurrence from necrosis after radiotherapy. METHODS: Fifty-five patients with suspected brain tumor recurrence or necrosis after radiotherapy underwent MRI, F-18 FDG, and 11C choline PET/CT examinations, and all the patients were followed up for at least 11 months. Lesion diagnoses based on medical imaging were compared with pathology or follow-up outcomes. RESULTS: The sensitivities of MRI, F-18 FDG PET/CT, and 11C-Choline PET/CT in lesion diagnosis were 87.2%, 76.9%, and 92.3%, respectively, and their specificities were 81.3%, 62.5%, and 87.5%, respectively. CONCLUSION: The results suggest that 11C-Choline PET/CT with higher sensitivity and specificity may be better in distinguishing recurrent brain tumor from radionecrosis compared with F-18 FDG PET/CT and MRI. PMID- 21975384 TI - Thallium-201 scintigraphy is an effective diagnostic modality to distinguish malignant from benign soft-tissue tumors. AB - BACKGROUND: The aim of this study is to evaluate whether thallium-201 (201-Tl) scintigraphy can differentiate malignant from benign soft-tissue tumors. METHODS: Between April 1995 and December 2005, 192 patients with soft-tissue tumors (85 malignant and 107 benign) underwent 201-Tl scintigraphy before treatment. Isotope uptake was used as a proxy for tumor-to-background ratio (TBR). The accuracy of TBR on early and delayed imaging was evaluated using the Mann-Whitney U and chi(2) tests. RESULTS: There was a statistically significant difference in mean TBR on early and delayed imaging of malignant and benign soft-tissue tumors (124% +/- 109% vs. 22% +/- 42%, and 82% +/- 83% vs. 12% +/- 25%, P < 0.0001). A TBR cutoff of 20% indicated the probability of malignancy on early and delayed imaging (82% sensitivity and 77% specificity; 82% sensitivity and 84% specificity, P < 0.0001). Well-differentiated liposarcomas showed low isotope accumulation, while pigmented villonodular synovitis and giant cell tumors of the tendon sheath showed high isotope accumulation. CONCLUSIONS: Thallium-201 scintigraphy can distinguish malignant from benign tumors with relatively high accuracy. With the exception of low grade liposarcomas and locally aggressive benign tumors, 201-Tl scintigraphy may be an effective diagnostic modality to differentiate malignant from benign soft-tissue tumors. PMID- 21975385 TI - Tc-99m red blood cell bleeding scan in a pregnant woman presenting with hematemesis: a brief review of indications and guidelines for radionuclide scans during pregnancy. AB - A 6-month pregnant 35-year-old woman with hematemesis and dark blood in her stool was evaluated for location of an active gastrointestinal bleeding site. The findings from 2 esophagogastroduodenoscopies and a colonoscopy were negative. The patient was referred for a Tc-99m red blood cell scintigraphy, for location of an active bleeding site. As the patient was 6 months pregnant, the necessity of the case was discussed with the patient's referring physician and after determining that this study was necessary, the risk of radiation exposure to the fetus was discussed with the radiation safety officer and the patient. The procedure was performed after the patient signed informed consent regarding the considerations of radiation safety to the fetus. The Tc-99m red blood cell bleeding scan clearly shows activity in the fetus in addition to a large arteriovenous malformation in the patient. The visualized fetus prompted this report to discuss radiation risks concerns and a brief review of indications and guidelines for performing nuclear medicine procedures in pregnant patients. PMID- 21975386 TI - Quantitative evaluation of striatal I-123-FP-CIT uptake in essential tremor and parkinsonism. AB - AIM: The aim of this study was to quantitatively evaluate the striatal uptake in 3 groups of patients: essential tremor (ET), drug-induced parkinsonism (DIP), and Parkinson disease (PD), using a voxel-based methodology and volumes of interests (VOIs) analysis. PATIENTS AND METHOD: Sixty patients from the Neurology Department Movement Disorders outpatient clinic in a tertiary hospital with I-123 FP-CIT SPECT were selected. After a clinical follow-up period of 2 years, a final clinical diagnosis of DIP was established for 20 patients (first group); 20 patients were diagnosed with ET (second group), and the third group was made up of 20 patients with a qualitatively pathologic SPECT who were diagnosed with PD.Once processed, DIP studies were spatially normalized to Montreal Neurologic Institute space and an average image was computed to create an I-123-FP-CIT SPECT template using statistical parametric mapping (SPM). Then all the I-123-FP-CIT images from all groups (DIP, ET, and PD) were registered to the new template. VOIs were defined in a digital atlas in Montreal Neurologic Institute space (caudate nucleus, putamen, and occipital cortex). Finally, mean counts were extracted from all VOIs and putamen-occipital and caudate-occipital ratios were computed. Analysis of variance tests were performed with all ratios.A SPM study of patterns evaluated the efficacy of the automated technique to determine whether the significant differences among groups corresponded to the same regions that the method purported to evaluate. RESULTS: The analysis of variance test revealed significant differences between DIP and ET as compared with PD, both in the putamen and in the caudate nucleus. There were significant differences between DIP and ET populations only in the putamen but not in the caudate.The SPM found a lower uptake in the PD group in comparison with the ET and DIP groups. Therefore, in the organic parkinsonism cases, the most significant changes in uptake decrease were found in the putamen nuclei when compared with the DIP and the ET cases. No significant changes were observed between the ET and DIP groups. CONCLUSIONS: This study provides a fairly simple, reproducible, and useful methodology to be applied in everyday practice to quantify the studies of dopamine transporters using FP-CIT.We present the different ratios for putamen and caudate nucleus for 3 different groups with FP-CIT images. We obtained an optimal discrimination threshold value between the reference population and the pathologic population for the putamen ratio. PMID- 21975387 TI - The usefulness of Tc-99m-tetrofosmin SPECT/CT in the detection of residual tumors and axillary lymph node metastases in breast cancer patients following neoadjuvant therapy. AB - Single photon emission computed tomography (SPECT)/CT is emerging as a useful diagnostic tool in several oncological fields. In this prospective study, we assessed the usefulness of Tc-99m-tetrofosmin SPECT/CT in the detection of both residual breast tumors and axillary lymph node metastases following neoadjuvant therapy. Thirty-seven consecutive breast cancer patients scheduled to surgery following neoadjuvant therapy preoperatively underwent a Tc-99m-tetrofosmin SPECT/CT study, using a dual head gamma camera integrated with a x-ray tube for low-dose CT, including both breasts and axillary regions in the field of view. Within 1 week of SPECT/CT, all 37 patients had breast surgery with associated axillary lymph node dissection in 33/37 cases. At surgery, 31/37 patients had breast residues (microscopic in 4/31 cases and macroscopic in 27/31 cases). Axillary lymph node metastases were ascertained in 19/33 cases (N1mi: 2 cases, N1a: 8 cases, N2a: 6 cases, N2b: 3 cases). SPECT/CT sensitivity, specificity, and accuracy in detecting residual tumors were 87%, 100%, and 89.2%, respectively; the corresponding values in detecting axillary lymph node metastases were 36.8%, 92.8%, and 60.6%. SPECT/CT missed breast cancer residues in 4/31 patients, including 2 cases with microscopic residual disease. Moreover, lymph node metastases were missed in 12/19 patients (10/12 with pN1mi or pN1a metastases), all with lymph nodes with post-therapy fibrotic changes and small deposits of metastases. Tc-99m-tetrofosmin SPECT/CT proved a useful diagnostic tool in the detection and in the localization of residual breast tumors following neoadjuvant therapy. The procedure lacked in sensitivity in identifying axillary lymph node metastases, especially in patients with a limited lymph node involvement. According to our data, SPECT/CT may guide the surgeon to the most appropriate breast surgical treatment and to eventually select the most suitable axillary lymph node sampling (axillary lymph node dissection or sentinel node biopsy). PMID- 21975388 TI - 13N-NH3 versus F-18 FDG in detection of intracranial meningioma: initial report. AB - PURPOSE: Relatively high Tl-201 uptakes have been reported in all types of meningiomas, and it have been proposed that (201)TlCl SPECT could predict histologic types of meningiomas and differentiate the benign and aggressive meningiomas. Similar to Tl-201, (13)N-(13)NH(4)(+) is an analog of K(+) and could substitute K(+) in some cases. The aim of this study was to evaluate the capacity of PET with (13)N-NH(3) to discriminate meningioma from healthy tissue, and compare with F-18 FDG. METHODS: Eleven patients with the neuroradiologic diagnosis of meningiomas were studied with (13)N-NH(3), and 10 of them were performed with F-18 FDG PET within 3 days. Ten of them were histologically confirmed (6 grade I, 4 grade II), and another one was proved by radiologic (computed tomography and magnetic resonance imaging) and clinical investigation.The PET images were evaluated by semiquantitative analysis using tumor-to-white matter ratio (T/W). RESULTS: (13)N-NH(3) uptake was obviously increased in all 11 meningiomas with a good contrast to the surrounding normal brain tissues. Conversely, F-18 FDG uptake was decreased in comparison with the contralateral side in all 7 patients with grade I meningiomas and moderately increased in the remaining patient with grade II meningioma. The T/W ratio of (13)N-NH(3) was higher than that of F-18 FDG (7.03 +/- 1.62 vs. 1.44 +/- 0.57, P < 0.005). T/W of (13)N-NH(3) uptake was not useful for differentiating benign (Grade I) from atypical (Grade II) meningiomas (P = 0.88), whereas the T/W ratio of F-18 FDG uptake was better than that of N-NH3 for differentiating benign from malignant meningiomas (P = 0.037). CONCLUSIONS: These preliminary results suggest that (13)N-NH(3) has relatively greater uptake in meningiomas in comparison with F-18 FDG. Clinical applications of (13)N-NH(3) PET for grading and follow-up of meningiomas need to be assessed in further studies. PMID- 21975389 TI - Prognostic impact of standardized uptake value of F-18 FDG PET/CT in nasopharyngeal carcinoma. AB - PURPOSE: We evaluated the use of metabolic parameters of F-18 fluorodeoxyglucose positron emission tomography (FDG PET) for the assessment of the primary tumor and nodal metastasis in predicting survival in nasopharyngeal carcinoma (NPC) patients. MATERIALS AND METHODS: The F-18 FDG PET/CT (computed tomography) scans of 46 consecutive newly diagnosed NPC patients were retrospectively reviewed. Maximal standardized uptake value (SUVmax) corrected for lean body mass of primary tumor (pSUVmax) and highest SUVmax of cervical lymph nodes (nSUVmax) were recorded. The association of FDG uptake and 2-year disease-free survival (DFS) was examined. RESULTS: Significantly better DFS was found in patients with pSUVmax <7.5 and nSUVmax <6.5 (P = 0.042 and P = 0.019, respectively). In multivariate analysis, both pSUVmax and nSUVmax were significant independent predictors of DFS. CONCLUSIONS: The SUVmax of the primary tumor and nodal metastasis are useful parameters for predicting DFS in NPC patients. PMID- 21975391 TI - Tips for leaders part IV: managing oneself and interacting well with others. AB - It is important that a leader assesses his strengths and weaknesses and evaluates where and how he does well. It is also important that a leader is aware of his emotions and is able to use that to better manage himself. Finally, a leader should be aware of the emotions of others, feel and show empathy, and use that understanding to exhibit better leadership within groups of people. This is referred to as emotional intelligence. This article examines these principles. PMID- 21975390 TI - Estimation of Tc-99m MAG3 clearance using camera-based methods without blood sampling. AB - PURPOSE: To establish camera-based methods for estimating Tc-99m mercaptoacetyltriglycine (MAG3) clearance without blood sampling. MATERIALS AND METHODS: The results of renal scintigraphy with Tc-99m MAG3 obtained from 160 patients were analyzed retrospectively. Eight renogram parameters were calculated for each patient based on the area under the renogram (area method) and slope of the renogram (slope method) using different periods for analysis (1-2 and 1-2.5 minutes for the area method; 0.5-1.5 and 0.5-2 minutes for the slope method) and different backgrounds for subtraction (perirenal and subrenal backgrounds). The 8 parameters were then correlated with MAG3 clearance measured by the single-sample methods proposed by Russell et al and Bubeck et al to determine the equation for the conversion of renogram parameters to clearance. RESULTS: All 8 renogram parameters were highly correlated with clearance measured by the single-sample methods, and the obtained equations enabled the estimation of clearance from image data. Selection between the area and slope methods, between different periods for analysis, or between perirenal and subrenal backgrounds did not cause large differences in the estimation. CONCLUSION: The camera-based methods determined in the present study allow the estimation of MAG3 clearance with acceptable accuracy. PMID- 21975392 TI - Tc-99m and I-131 uptake in widespread bone metastases from undetectable digestive adenocarcinoma. PMID- 21975393 TI - Radiotracer visualization within a saline breast implant due to inadvertent needle penetration during lymphoscintigraphy. PMID- 21975394 TI - Oncocytic carcinoid of the kidney positively detected by I-131 MIBG scintigraphy. PMID- 21975395 TI - Tc-99m MDP uptake in a giant pulmonary chondroma. PMID- 21975396 TI - Scrotal lymphedema mimicking urine leakage. PMID- 21975397 TI - Bone metastasis from thyroid cancer diagnosed by I-131 whole-body scan without identifiable lesion in the thyroid. PMID- 21975398 TI - False-positive F-18 FDG PET/CT from foreign body reaction on anterior chest wall after endoscopic total thyroidectomy via axillo-breast approach for thyroid cancer: two case reports. PMID- 21975399 TI - Graves' disease in a patient with ectopic mediastinal thyroid. PMID- 21975400 TI - Diffuse splenic F-18 FDG uptake in visceral leishmaniasis. PMID- 21975401 TI - Secondary retroperitoneal fibrosis due to polyarteritis nodosa evaluated by F-18 FDG PET/CT. PMID- 21975402 TI - Superscan pattern of F-18 sodium fluoride PET/CT study in a case of prostate cancer. PMID- 21975403 TI - PET scan: findings in a patient with severe cutaneous and systemic sarcoidosis. PMID- 21975404 TI - Metabolic pattern of glomic tumor by F-18 FDG PET/CT. PMID- 21975405 TI - A low F-18 FDG uptake in the nasopharynx plasmacytoma detected by FDG PET/CT. PMID- 21975406 TI - Tc-99m human serum albumin lymphoscintigraphy with SPECT/CT in chylothorax. PMID- 21975407 TI - Imaging features of adult neuroblastoma in F-18 FDG PET/CT. PMID- 21975408 TI - Intraosseous lipoma of rib with intense radiotracer uptake on bone scintigraphy. PMID- 21975409 TI - In vivo visualization of somatostatin receptor expression with Ga-68-DOTA-TATE PET/CT in advanced metastatic prostate cancer. PMID- 21975410 TI - Unexpected gallbladder emptying from visual stimulation: controlling sensory factors in hepatobiliary scintigraphy. PMID- 21975411 TI - Current readings in nuclear medicine. PMID- 21975412 TI - Use of F-18 fluoride PET to differentiate septic from aseptic loosening in total hip arthroplasty patients. AB - PURPOSE: The preoperative differentiation of aseptic and septic loosening following a total hip arthroplasty (THA) remains a challenging issue for clinicians to which several molecular imaging techniques have been applied. In our current study, we used F-18 fluoride positron emission tomography (PET) to evaluate THA cases with stable, septic or septic loosened implants to assess the possibility of differentiating these clinical settings using a novel uptake-type classification approach. MATERIALS AND METHODS: A total of 65 joints were enrolled in this prospective study comprising 27 asymptomatic stable hips (control group), 11 painful hips conservatively treated after THA due to a suspicion of loosening, and 27 painful hips surgically treated after THA. PET imaging was classified into 3 types according to the uptake pattern. The maximum standardized uptake value (SUVmax) was then measured for each joint. A final diagnosis was made via tissue examinations of surgically treated cases, and by serological and radiographic findings in conservatively treated cases. RESULTS: There were significant differences found between the SUVmax values for the aseptic and septic loosening THA cases. In the diagnosis of infection with type 3 pattern, the sensitivity and specificity were measured at 0.95 and 0.98 for all cases, and 0.95 and 0.88 for surgically treated cases, respectively. CONCLUSIONS: The results of our current study demonstrate that F-18 fluoride PET has considerable potential as a method for differentiating septic from aseptic loosening following a THA. The type classification of the uptake pattern can be performed relatively simply, and quantifications using the SUVmax values can then provide an objective evaluation. PMID- 21975413 TI - Congenital agenesis of right parotid gland confounds MIBG scan interpretation in craniocervical neuroblastoma. AB - A 10-month-old boy with left infraorbital temporal neuroblastoma presented for I 123 metaiodobenzylguanidine scan with SPECT/CT for staging. Symmetrical metaiodobenzylguanidine uptake in salivary glands is usually considered normal. In this case of right parotid agenesis, symmetrical uptake was misleading. Tumor in the right mandibular ramus masqueraded as normal parotid gland. Repeat imaging 3 months after chemotherapy revealed absence of physiologic right parotid gland activity. Correlation with CT from SPECT/CT demonstrated right parotid agenesis, confirmed on MRI. Few cases of unilateral parotid agenesis are reported in published literature. We also discuss the potential added value of higher-quality CT images in SPECT/CT tumor imaging. PMID- 21975414 TI - Splenic-gonadal fusion in a 6-year-old boy, confirmed by Tc-99m sulfur colloid scanning. AB - Splenic-gonadal fusion is a rare congenital anomaly, in which splenic tissue is connected to the gonad. It is almost always on the left side, is difficult to be recognized, and unfortunately the final diagnosis is confirmed after an unnecessary orchiectomy in one-third of the cases. We report a case of splenic gonadal fusion in a 6-year-old boy, referred for a palpable mass at the left testicle. Ultrasound and MRI were performed; and the final diagnosis was confirmed by Tc-99m colloid scanning. The child was operated, orchiectomy was avoided, the mass was removed, and pathology confirmed normal splenic tissue. PMID- 21975415 TI - Rib fracture following stereotactic body radiotherapy: a potential pitfall. AB - Although the incidence of rib fractures after conventional radiotherapy is generally low (<2%), rib fractures are a relatively common complication of stereotactic body radiotherapy. For malignancy adjacent to the chest wall, the incidence of rib fractures after stereotactic body radiotherapy is as high as 10%. Unrecognized bone fractures can mimic bone metastases on bone scintigraphy, can lead to extensive workup, and can even lead to consideration of unnecessary systemic chemotherapy, as treatment decisions can be based on imaging findings alone. Nuclear medicine physicians and diagnostic radiologists should always consider rib fracture in the differential diagnosis. PMID- 21975416 TI - Synchronous squamous cell carcinomas of the esophagus and renal pelvis. AB - A 55-year-old man was incidentally diagnosed with a superficial squamous cell carcinoma of esophagus. However, the systemic survey with FDG PET/CT revealed a picture of more advanced disease because of the regional lymph node metastases and a suspected distal metastasis in the left renal pelvis, which was somewhat strange for a small superficial esophageal cancer. Subsequently, the renal pelvic lesion was confirmed as squamous cell carcinoma. However, a primary tumor rather than metastasis in the renal pelvis was considered according to the histologic characteristics and radiologic findings. PMID- 21975417 TI - Intense focal F-18 FDG uptake in vocal cord associated with injection of calcium hydroxylapatite microspheres. AB - Lower F-18 fluorodeoxyglucose (FDG) uptake on PET/CT is generally expected on the side of a paralyzed vocal cord (VC). The contrary pattern of increased uptake can raise concern for metastasis or a primary VC malignancy. We present a case showing paradoxical development of intense FDG uptake in the paralyzed VC, unrelated to malignancy. History revealed injection of calcium hydroxylapatite microspheres for treatment of VC paralysis. This new synthetic material can stimulate local fibroblast activity and macrophage accumulation, leading to increased FDG uptake. The case illustrates the importance of obtaining accurate history before interpreting intense FDG uptake in a paralyzed VC. PMID- 21975418 TI - Brain SPECT thallium using cadmium zinc telluride: a first experience. AB - A 70-year-old man underwent a thallium-201 brain SPECT in the work-up and characterization of a frontotemporal mass. SPECT images were performed on cadmium zinc telluride system during only 5 minutes and after the injection of only 2 mCi. Images demonstrated high thallium uptake in frontotemporal areas considered as a potential malignant tumor. Surgical removal confirmed the diagnosis of malignant glioblastoma. The thallium SPECT fast acquisition imaging on cadmium zinc telluride systems is feasible with reduced injected dose. This method allows a significantly decrease of patient radiation exposure without compromising the image quality. This initial experience needs to be confirmed and optimized in larger clinical studies. PMID- 21975419 TI - Persons with multiple sclerosis show altered joint kinetics during walking after participating in elliptical exercise. AB - Patients with multiple sclerosis (MS) experience abnormal gait patterns and reduced physical activity. The purpose of this study was to determine if an elliptical exercise intervention for patients with MS would change joint kinetics during gait toward healthy control values. Gait analysis was performed on patients with MS (n = 24) before and after completion of 15 sessions of supervised exercise. Joint torques and powers were calculated, while also using walking velocity as a covariate, to determine the effects of elliptical exercise on lower extremity joint kinetics during gait. Results show that elliptical exercise significantly altered joint torques at the ankle and hip and joint powers at the ankle during stance. The change in joint power at the ankle indicates that, after training, patients with MS employed a walking strategy that is more similar to that of healthy young adults. These results support the use of elliptical exercise as a gait training tool for patients with MS. PMID- 21975420 TI - Dermatofibrosarcoma presenting as a nodule in the breast of a 75-year-old woman: a case report. AB - INTRODUCTION: Dermatofibrosarcoma protuberans is a rare neoplasm of soft tissues and its location in the breast is extremely uncommon. Confusion is possible with other primary breast lesions. CASE PRESENTATION: A 75-year-old Caucasian woman presented with a mass in her left breast 21 years after being diagnosed with invasive ductal carcinoma of the right breast, treated by a right mastectomy and axillary dissection followed by radiotherapy and breast reconstruction. Mammography revealed a dish-shaped skin nodule formation in the upper outer quadrant of her left breast. Echography confirmed the presence of a lesion measuring 1.4 * 0.8 cm. Based on imaging, the diagnosis was a probable angiosarcoma. Due to the presence of a pacemaker for cardiac arrhythmia and full anticoagulation therapy for a pulmonary embolism, magnetic resonance imaging and a biopsy were not done. We proceeded directly to a quadrantectomy and the final diagnosis revealed a dermatofibrosarcoma protuberans, 1. 8 cm in its greatest microscopic dimension, located 0.1 cm from the upper surgical margin. To ensure the wide resection margins required for this type of neoplasm, a re-excision was performed. CONCLUSION: A dermatofibrosarcoma protuberans of the breast is an uncommon discovery. The aim of this case report is to highlight the importance of the surgical procedure in cases of the discovery of dermatofibrosarcoma protuberans. Re-excision may be necessary to ensure adequate resection margins. PMID- 21975421 TI - Crystal violet as a G-quadruplex-selective probe for sensitive amperometric sensing of lead. AB - A sensitive and selective amperometric sensing platform for lead (Pb(2+)) was developed based on a Pb(2+)-induced G-rich DNA conformational switch from a random-coil to G-quadruplex (G4) with crystal violet as the G4-binding indicator. PMID- 21975422 TI - On the organizing role of nonmuscular forces during performance of a giant circle in gymnastics. AB - Five elite gymnasts performed giant circles on the high bar under different conditions of loading (without and with 6-kg loads attached to the shoulders, waist or ankles). Comparing the gymnasts' kinematic pattern of movement with that of a triple-pendulum moving under the sole influence of nonmuscular forces revealed qualitative similarities, including the adoption of an arched position during the downswing and a piked position during the upswing. The structuring role of nonmuscular forces in the organization of movement was further reinforced by the results of an inverse dynamics analysis, assessing the contributions of gravitational, inertial and muscular components to the net joint torques. Adding loads at the level of the shoulders, waist or ankles systematically influenced movement kinematics and net joint torques. However, with the loads attached at the level of the shoulders or waist, the load-induced changes in gravitational and inertial torques provided the required increase in net joint torque, thereby allowing the muscular torques to remain unchanged. With the loads attached at the level of the ankles, this was no longer the case and the gymnasts increased the muscular torques at the shoulder and hip joints. Together, these results demonstrate that expert gymnasts skillfully exploit the operative nonmuscular forces, employing muscle force only in the capacity of complementary forces needed to perform the task. PMID- 21975423 TI - Enantioselective methodologies for the synthesis of spiro compounds. AB - The enantioselective synthesis of spirocycles has been a long time pursued dream for organic chemists. Since the first pioneering efforts of Tamao and coworkers in the enantioselective construction of spirosilanes, many efforts have been devoted to the development of new and promising asymmetric methodologies. Remarkably, with the advent of organocatalysis the number of methodologies has been highly increased. The aim of this tutorial review is to summarize the last trends and developments reported in the literature in the enantioselective synthesis of spirocompounds. PMID- 21975424 TI - Skeletal muscle regeneration is delayed by reduction in Xin expression: consequence of impaired satellite cell activation? AB - Xin is a striated muscle-specific actin-binding protein whose mRNA expression has been observed in damaged skeletal muscle. Here we demonstrate increased Xin protein expression early postinjury (<= 12 h) and localization primarily to the periphery of damaged myofibers. At 1 day postinjury, Xin is colocalized with MyoD, confirming expression in activated satellite cells (SCs). By 5 days postinjury, Xin is evident in newly regenerated myofibers, with a return to preinjury levels by 14 days of regeneration. To determine whether the increased Xin expression is functionally relevant, tibialis anterior muscles of wild-type mice were infected with Xin-short hairpin RNA (shRNA) adenovirus, whereas the contralateral tibialis anterior received control adenovirus (Control). Four days postinfection, muscles were harvested or injured with cardiotoxin and collected at 3, 5, or 14 days thereafter. When compared with Control, Xin-shRNA infection attenuated muscle regeneration as demonstrated by Myh3 expression and fiber areas. Given the colocalization of Xin and MyoD, we isolated single myofibers from infected muscles to investigate the effect of silencing Xin on SC function. Relative to Control, SC activation, but not proliferation, was significantly impaired in Xin-shRNA-infected muscles. To determine whether Xin affects the G0 G1 transition, cell cycle reentry was assessed on infected C2C12 myoblasts using a methylcellulose assay. No difference in reentry was noted between groups, suggesting that Xin contributes to SC activation by means other than affecting G0 G1 transition. Together these data demonstrate a critical role for Xin in SC activation and reduction in Xin expression results in attenuated skeletal muscle repair. PMID- 21975425 TI - The elusive phosphotyrosine: pinning down a rare species. Focus on "Large-scale phosphotyrosine proteomic profiling of rat renal collecting duct epithelium reveals predominance of proteins involved in cell polarity determination". PMID- 21975426 TI - Absolute amounts and diffusibility of HSP72, HSP25, and alphaB-crystallin in fast and slow-twitch skeletal muscle fibers of rat. AB - Heat shock proteins (HSPs) are essential for normal cellular stress responses. Absolute amounts of HSP72, HSP25, and alphaB-crystallin in rat extensor digitorum longus (EDL) and soleus (SOL) muscle were ascertained by quantitative Western blotting to better understand their respective capabilities and limitations. HSP72 content of EDL and SOL muscle was only ~1.1 and 4.6 MUmol/kg wet wt, respectively, and HSP25 content approximately twofold greater (~3.4 and ~8.9 MUmol/kg, respectively). alphaB-crystallin content of EDL muscle was ~4.9 MUmol/kg but in SOL muscle was ~30-fold higher (~140 MUmol/kg). To examine fiber heterogeneity, HSP content was also assessed in individual fiber segments; every EDL type II fiber had less of each HSP than any SOL type I fiber, whereas the two SOL type II fibers examined were indistinguishable from the EDL type II fibers. Sarcolemma removal (fiber skinning) demonstrated that 10-20% of HSP25 and alphaB crystallin was sarcolemma-associated in SOL fibers. HSP diffusibility was assessed from the extent and rate of diffusion out of skinned fiber segments. In unstressed SOL fibers, 70-90% of each HSP was readily diffusible, whereas ~95% remained tightly bound in fibers from SOL muscles heated to 45 degrees C. Membrane disruption with Triton X-100 allowed dispersion of HSP72 and sarco(endo)plasmic reticulum Ca(2+)-ATPase pumps but did not alter binding of HSP25 or alphaB-crystallin. The amount of HSP72 in unstressed EDL muscle is much less than the number of its putative binding sites, whereas SOL type I fibers contain large amounts of alphaB-crystallin, suggesting its importance in normal cellular function without upregulation. PMID- 21975427 TI - Activation of Wnt3a signaling stimulates intestinal epithelial repair by promoting c-Myc-regulated gene expression. AB - In response to mucosal injury, epithelial cells modify the patterns of expressed genes to repair damaged tissue rapidly. Our previous studies have demonstrated that the transcription factor c-Myc is necessary for stimulation of epithelial cell renewal during mucosal healing, but the up-stream signaling initiating c-Myc gene expression after injury remains unknown. Wnts are cysteine-rich glycoproteins that act as short-range ligands to locally activate receptor mediated signaling pathways and correlate with the increased expression of the c Myc gene. The current study tested the hypothesis that Wnt3a signaling is implicated in intestinal epithelial repair after wounding by stimulating c-Myc expression. Elevated Wnt3a signaling in intestinal epithelial cells (IEC-6 line) by coculturing with stable Wnt3a-transfected fibroblasts or ectopic overexpression of the Wnt3a gene enhanced intestinal epithelial repair after wounding. This stimulatory effect on epithelial repair was prevented by silencing the Wnt coreceptor LRP6 or by c-Myc silencing. Activation of the Wnt3a signaling pathway increased beta-catenin nuclear translocation by decreasing its phosphorylation and stimulated c-Myc expression during epithelial repair after wounding. In stable Wnt3a-transfected IEC-6 cells, increased levels of c-Myc were associated with an increase in expression of c-Myc-regulated genes cyclcin D1 and cyclin E, whereas c-Myc silencing inhibited expression of cyclin D1 and cyclin E and delayed epithelial repair. These results indicate that elevated Wnt3a signaling in intestinal epithelial cells after wounding stimulates epithelial repair by promoting c-Myc-regulated gene expression. PMID- 21975428 TI - A novel route to copper(II) detection using 'click' chemistry-induced aggregation of gold nanoparticles. AB - A simple colorimetric method for the detection of copper ions in water is described. This method is based on the 'click' copper(I)-catalyzed azide-alkyne cycloaddition reaction and its use in promoting the aggregation of azide-tagged gold nanoparticles by a dialkyne cross-linker is described. Nanoparticle cross linking, evidenced as a colour change, is used for the detection of copper ions. The lowest detected concentration by the naked eye was 1.8 MUM, with the response linear with log(concentration) between 1.8-200 MUM. The selectivity relative to other potentially interfering ions was evaluated. PMID- 21975429 TI - Genetic variations and heterosexual HIV-1 infection: analysis of clustered genes encoding CC-motif chemokine ligands. AB - Several CC-motif chemokine ligands (CCLs) can block HIV-1-binding sites on CC motif chemokine receptor 5 (CCR5) and inhibit viral entry. We studied single nucleotide polymorphisms (SNPs) in genes encoding three CCR5 ligands (CCL3 (MIP 1a), CCL4 (MIP-1b)and CCL5 (RANTES)) along with an adjacent gene encoding a CCR2ligand (CCL2 (MCP-1)) to identify candidate markers for HIV-1 infection and pathogenesis. Analyses of 567 HIV-1 serodiscordant Zambian couples revealed that rs5029410C (in CCL3 intron 2) was associated with lower viral load (VL) in seroconverters, adjusted for gender and age (regression beta=-0.57 log(10), P=4x10(-6)). Inaddition, rs34171309A in CCL3 exon 3 was associated with increased risk of HIV-1 acquisition in exposed seronegatives(hazard ratio=1.52, P=0.006 when adjusted for VL of the initially seropositive partner and genital ulcer/inflammation). SNPrs34171309 encodes a conservative Glu-to-Asp substitution. Fiven eighboring SNPs in tight linkage disequilibrium with rs34171309all showed similar associations with HIV-1 acquisition. How these multiple CCL3 SNPs may alter the occurrence or course of HIV-1 infection remains to be determined [corrected]. PMID- 21975430 TI - Genetic control of susceptibility to infection with Plasmodium chabaudi chabaudi AS in inbred mouse strains. AB - To identify genetic effects modulating the blood stage replication of the malarial parasite, we phenotyped a group of 25 inbred mouse strains for susceptibility to Plasmodium chabaudi chabaudi AS infection (peak parasitemia, survival). A broad spectrum of responses was observed, with strains such as C57BL/6J being the most resistant (low parasitemia, 100% survival) and strains such as NZW/LacJ and C3HeB/FeJ being extremely susceptible (very high parasitemia and uniform lethality). A number of strains showed intermediate phenotypes and gender-specific effects, suggestive of rich genetic diversity in response to malaria in inbred strains. An F2 progeny was generated from SM/J (susceptible) and C57BL/6J (resistant) parental strains, and was phenotyped for susceptibility to P. chabaudi chabaudi AS. A whole-genome scan in these animals identified the Char1 locus (LOD=7.40) on chromosome 9 as a key regulator of parasite density and pointed to a conserved 0.4-Mb haplotype at Char1 that segregates with susceptibility/resistance to infection. In addition, a second locus was detected in [SM/J * C57BL/6J] F2 mice on the X chromosome (LOD=4.26), which was given the temporary designation Char11. These studies identify a conserved role of Char1 in regulating response to malaria in inbred mouse strains, and provide a prioritized 0.4-Mb interval for the search of positional candidates. PMID- 21975431 TI - Methylation status of CpG sites in the MCP-1 promoter is correlated to serum MCP 1 in Type 2 diabetes. AB - AIM: Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine and plays an important role in atherosclerosis of Type 2 diabetes. The aim of this study was to investigate the methylation status of CpG sites in the MCP-1 promoter in Type 2 diabetic patients and its correlation to serum MCP- 1 level, and blood glucose level. METHODS: The 32 patients with Type 2 diabetes and 15 healthy controls were enrolled into the study. Bodymass index, blood pressure, blood lipid, blood glucose, glycosylated hemoglobin (HbA1c), and serum MCP-1 were measured. Genomic DNA was isolated fromthe peripheral blood mononuclear cells (PBMC). Methylation status of CpG sites in theMCP-1 promoter was determined using methylation specific polymerase chain reaction. RESULTS: The promoter region (2890-3050 bp) was predominantly methylated in PBMC from controls.Methylation of CpGmotifs were less methylated in the patients than in the controls (25% vs 80%; p<0.001), while the level of MCP-1 in serum was higher in patients with Type 2 diabetes (193.95+/-74.96 vs 88.46+/-55.10; p<0.001). MCP-1 promoter methylation was significantly correlated to serum MCP-1, HbA1c, fasting blood glucose, and triglyceride. CONCLUSION: These data suggest that hypomethylation of CpG sites in the MCP-1 promoter region may be affected by blood glucose and TG, which then increase the serum MCP-1 level and may play a role in the vascular complications of Type 2 diabetes. PMID- 21975432 TI - A rare case of perforated ileal diverticulitis. PMID- 21975433 TI - Chronic viral hepatitis and risk of lymphoid malignancies: a retrospective twelve year population-based cohort study in Cote d'Or, France. AB - BACKGROUND: The association between hepatitis C infection and lymphoid malignancies is still a matter of debate. The hypothesis of a relationship between hepatitis B and lymphoid neoplasms is more recent and has been far less thoroughly explored. AIM: The aim of this study was to evaluate the association between hepatitis C and B infections and B cell non-Hodgkin and Hodgkin lymphomas. METHODS: We took advantage of the co-existence in the French administrative area of Cote d'Or of two specialized registries - one for viral hepatitis and one for haematological diseases - to conduct a population-based, cohort study covering a 12-year period. The databases were anonymized and then linked using a probabilistic model. RESULTS: There were 8234 person-years at risk in the hepatitis C cohort and 2784 in the hepatitis B cohort. We found 6 cases of non-Hodgkin lymphoma in the hepatitis C cohort, resulting in an overall adjusted standardized incidence ratio of 3.42 (CI: 1.25-7.45). Three of these 6 cases were diffuse-large-B-cell-lymphoma. Cirrhosis was associated with a higher risk of non Hodgkin lymphoma in the hepatitis C cohort (relative risk=8.4, p<0.01, using a Poisson regression). We found one case of chronic lymphocytic leukaemia amongst the hepatitis B carriers. CONCLUSION: Hepatitis C carriers are at a higher risk of developing non-Hodgkin lymphoma than the general population. The role of cirrhosis and the association between hepatitis B and lymphoid malignancies deserve to be further assessed. PMID- 21975434 TI - Liver metastases of pancreatic cancer: role of repetitive transarterial chemoembolization (TACE) on tumor response and survival. AB - OBJECTIVE: To evaluate the effect of chemoembolization on pancreatic cancer liver metastases. METHOD: Thirty-two patients with pancreatic cancer liver metastases retrospectively underwent chemoembolization (4- to 8-week intervals). Size-based evaluation (response evaluation criteria in solid tumors [RECIST]) and survival indexes were assessed overall and for sex and number of lesions. RESULTS: Of the patients, 71.87% showed stable disease, 9.37% partial response (PR) and 18.75% progressive disease (PD). Survival rate for 1, 3, and 5 years from first TACE was 60%, 25%, and 11%, respectively. Median survival time was 16 months and for stable disease group was 20 months. Progression-free survival for 6 months and 1, 3, and 5 years was 84%, 57.3%, 20%, and 10%, respectively. There was significant difference between men and women in response. Survival rates for 1 and 5 years for the men were 80% and 14% and for the women were 47% and 0%. There was no significant difference between oligonodular liver lesion (n < 5) and multinodular (n > 5) groups. Survival rates for 1 and 5 years for oligonodular were 84% and 14%, and for multinodular was 50% and 0%. CONCLUSION: Repetitive TACE resulted in a relevant response for the control of liver metastases of pancreatic cancer with respectable median survival time. Interestingly, the number of lesions, statistically, was not an effective factor. PMID- 21975435 TI - Prognostic clinicopathologic factors in longitudinally followed patients with metastatic small bowel carcinoid tumors. AB - OBJECTIVES: Neuroendocrine tumors demonstrate heterogeneous behavior based on the site of origin and histology. This study aimed to delineate prognostic clinicopathologic features in patients with metastatic midgut carcinoid. METHODS: All patients underwent resection of the primary tumor in the setting of metastatic disease. Survival was measured from the date of primary tumor resection and calculated by Kaplan-Meier estimation. Clinical data include age, sex, serum biomarkers, primary tumor size, Ki-67 index, and the performance of hepatic cytoreductive procedure. Serially collected serum biomarkers were considered as mean values within periods relative to primary resection: preoperative, 0 to 1 year postoperative, and years 1 to 5 postoperative. Log-rank comparisons were used to assess the prognostic value of the aforementioned features. RESULTS: Forty-nine patients (21 men) with metastatic midgut carcinoid who underwent primary tumor resection were identified. Median survival was 121 months. The overall 5-year survival rate was 83%. Age higher than 65 years (P = 0.01) and late postoperative chromogranin A (CgA; P = 0.02) were associated with decreased survival. CONCLUSIONS: This study highlights the favorable prognosis of patients with metastatic small bowel carcinoid in a multidisciplinary treatment program. Among other factors, elevated postoperative CgA is associated with decreased survival. The significance of increased CgA over time underlies the importance of longitudinal follow-up for these patients. PMID- 21975436 TI - Autoimmune pancreatitis (AIP) type 1 and type 2: an international consensus study on histopathologic diagnostic criteria. AB - OBJECTIVES: To develop and validate histologic diagnostic criteria for autoimmune pancreatitis (AIP) and its types. METHODS: Thirteen pathologists participated in this 2-phase study to develop diagnostic criteria for AIP types 1 and 2 (phase 1) and validate them (phase 2). A virtual library of 40 resected pancreata with AIP and other forms of chronic pancreatitis (CP) was constructed. Readers reviewed the slides online and filled out a questionnaire for histopathologic findings and diagnosis. RESULTS: Diagnostic criteria for AIP and its types were proposed according to the results from the top 5 reviewers in phase 1. The interobserver agreement was significantly improved in phase 2 by applying the proposed diagnostic criteria. Features distinguishing AIP from alcoholic and obstructive forms of CP were periductal lymphoplasmacytic infiltrate, inflamed cellular stroma with storiform fibrosis, obliterative phlebitis, and granulocytic epithelial lesions. Although there was overlap, 2 types of AIP were recognized. Type 1 had dense lymphoplasmacytic infiltrate with storiform fibrosis and obliterative phlebitis, whereas type 2 was distinguished from type 1 by the presence of granulocytic epithelial lesions. CONCLUSIONS: Autoimmune pancreatitis can be distinguished from other forms of CP with substantial interobserver agreement. The 2 types of AIP can be distinguished by the proposed consensus histopathologic diagnostic criteria. PMID- 21975437 TI - Prognostic impact of left ventricular mass severity according to the classification proposed by the American Society of Echocardiography/European Association of Echocardiography. AB - BACKGROUND: The American Society of Echocardiography (ASE) and European Association of Echocardiography (EAE) recommend the use of quantitative estimation of left ventricular (LV) mass and defined partition values for mild, moderate, and severe hypertrophy. However, the prognostic implications associated with this categorization are unknown. METHODS: In this observational cohort study of unselected adults undergoing echocardiography for any indication, LV hypertrophy was assessed using the ASE/EAE-recommended formula and measurement convention from LV linear dimensions indexed to body surface area. Mortality and incident hospitalizations for cardiovascular disease were the outcomes of this study. RESULTS: Of 2,545 subjects (mean age, 61.9 +/- 15.8 years; 56.3% women), 52.9% had normal LV mass, and 15.4% had mild, 12.1% moderate, and 19.6% severe LV hypertrophy. During a mean follow-up period of 2.5 +/- 1.2 years, 121 deaths and 292 incident hospitalizations for cardiovascular disease occurred. In multivariate models including age, gender, LV ejection fraction, wall motion score index, significant valvular disease, and atrial fibrillation, the adjusted hazard ratios for death were 1.81 (95% confidence interval [CI], 1.03-3.20; P = .041) for mild, 2.31 (95% CI, 1.33-4.01; P = .003) for moderate, and 2.30 (95% CI, 1.39-3.79, P = .001) for severe LV hypertrophy. The adjusted hazard ratios for incident cardiovascular hospitalizations were 1.24 (95% CI, 0.84-1.82; P = .277) for mild, 2.02 (95% CI, 1.42-2.88; P = .0001) for moderate, and 2.38 (95% CI, 1.75-3.22, P < .0001) for severe LV hypertrophy. After adjustment for known risk predictors, there was a 1.3-fold risk for death and cardiovascular disease events per category of LV mass (P = .001). CONCLUSIONS: In a cohort study of unselected adult outpatients, the categorization of LV mass according to the ASE/EAE recommendations offered prognostic information independently of age, gender, and other known predictors. PMID- 21975438 TI - Electronic transport through side-contacted graphene nanoribbons: effects of overlap, aspect ratio and orientation. AB - We numerically calculate the conductance and shot noise Fano factor of graphene nanoribbons (GNRs) side-contacted to metallic leads. A tight-binding model and Landauer's formalism are used in combination with a modified recursion method for Green's functions. The interfaces are modeled as a contact region between an infinite metallic electrode and a segment of the GNR put on top of it. The key question to answer in this study is how the size and orientation of the GNR and the GNR/electrode interface area influence the transport properties. It turns out that in general the transport characteristics depend strongly on overlap, meant as the ratio between the electrode-supported GNR length and the unsupported one. Moreover, a speed of convergence (with the overlap length) depends on both the transport direction and the aspect ratio of the GNR. It is shown that a short overlap interface is often, but not always, advantageous in nanoelectronics. These findings reconcile some seemingly conflicting opinions reported in the literature. PMID- 21975439 TI - Nickel-oxido structure of a water-oxidizing catalyst film. AB - The atomic structure of an electrodeposited Ni catalyst film is dominated by extensive di-MU-oxido bridging between Ni(III/IV) ions, as revealed by X-ray absorption spectroscopy. The structure is surprisingly similar to that of an analogous Co-based film and colloidal Mn-based catalysts. Structural requirements for water oxidation are discussed. PMID- 21975440 TI - Gene transfer using micellar nanovectors inhibits corneal neovascularization in vivo. AB - PURPOSE: The efficacy of gene therapy using nonviral vector based on polyplex micelle has been studied against corneal neovascularization in mice. METHODS: A block copolymer, poly(ethylene glycol) (PEG)-block-polycation carrying ethylenediamine units in the side chain (PEG-b-P[Asp(DET)]), was prepared. PEG-b P[Asp(DET)] formed a polyplex micelle through the polyion complex formation with plasmid DNA. To evaluate in vivo gene transfer efficiency, PEG-b-P[Asp(DET)] micelle was injected into the subconjunctival space of mice, and the expression of the reporter gene was assessed. Furthermore, mouse corneal neovascularization models were treated with the PEG-b-P[Asp(DET)] polyplex micelle containing expression plasmid vector of soluble vascular endothelial growth factor receptor 1 (sflt-1). RESULTS: Subconjunctival injection of the PEG-b-P[Asp(DET)] polyplex micelle containing a reporter gene showed prolonged gene expression with low cytotoxicity. Also, gene transfer into subconjunctival space by the polyplex micelle containing sflt-1 plasmid showed significant inhibition of corneal neovascularization in mice. CONCLUSIONS: Nonviral gene therapy using PEG-b P[Asp(DET)] polyplex micelle may have potential for safe and effective therapeutic treatment of corneal neovascularization. PMID- 21975441 TI - The distribution of corneal thickness in a 40- to 64-year-old population of Shahroud, Iran. AB - PURPOSE: To determine the distribution of central and peripheral corneal thickness values and its determinants in an Iranian population. METHODS: This population-based study was conducted between 2009 and 2010 in Shahroud, with a response rate of 82.2%. Here in, we present the data on central and peripheral corneal thickness in 3890 participants of the study, which included all 40- to 64 year-old participants except those with a history of ocular surgery. Measurements were done with the Pentacam, and correlations with age, gender, height, body mass index, and refraction were tested. RESULTS: The mean age (+/- standard deviation) of the participants was 50.7 years (+/- 6.2 years). Mean corneal thickness in the thinnest point, the center, and 3 mm away from it in the inferior, superior, nasal, and temporal directions were 525.5 +/- 35.9 MUm, 528.5 +/- 35.8 MUm, 608.2 +/- 39.8 MUm, 635.5 +/- 41.9 MUm, 611.7 +/- 43.2 MUm, and 601.0 +/- 40.4 MUm, respectively. The thinnest point was in the inferotemporal quadrant in 87.5% of cases. The center of the cornea was thinner than 500 MUm in 36.6% of myopic cases and 21.8% of hyperopic cases. The thickness and location difference between the center and thinnest point were statistically significant (P < 0.001). Central corneal thickness was directly correlated with refraction (P = 0.028) and inversely with age (P = 0.027). CONCLUSIONS: In this population-based study, the thinnest point was usually located inferotemporally and the thickest point superiorly. The peripheral cornea was significantly thicker than the central cornea but thinned faster with age. The thickness difference between the thinnest and central points was significantly greater in men. People with hyperopia had thicker corneas compared with those with myopia. PMID- 21975442 TI - Probing the kinome in real time with fluorescent peptides. AB - Protein phosphorylation is the most frequent post-translational modification used to regulate protein activity. Protein kinases, the enzymes that catalyze the phosphoryl transfer, are implicated in practically every aspect of normal as well as abnormal cell functions. Consequently, sensitive, selective, high-throughput and widely applicable methods for monitoring protein kinase activity will provide valuable tools to screen inhibitor candidates for therapeutics and chemical biology, and to unravel the diverse signaling cascades in which these enzymes are pivotal. Peptide-based chemosensors that rely on fluorescence changes upon phosphorylation are highly desirable, because these systems allow a continuous readout offering an excellent spatial and temporal resolution to observe in real time the kinase activity. This tutorial review briefly summarizes the different fluorescent continuous peptide-based strategies that are being commonly employed to sense protein phosphorylation, introduces a few novel and attractive emerging assays, discusses their advantages and limitations, and highlights possible future directions. PMID- 21975443 TI - Response to imatinib rechallenge in a patient with a recurrent gastrointestinal stromal tumor after adjuvant therapy: a case report. AB - INTRODUCTION: Adjuvant imatinib improves recurrence-free survival of patients following resection of primary KIT-positive gastrointestinal stromal tumors. However, it is unknown whether patients who previously received adjuvant imatinib therapy will respond to imatinib rechallenge as treatment for recurrent disease. Here we present the first report documenting the benefits of imatinib rechallenge in a patient previously exposed to imatinib during adjuvant treatment. CASE PRESENTATION: A 51-year-old Asian woman with a wedge-resected primary gastric gastrointestinal stromal tumor at high risk of relapse underwent two years of adjuvant treatment with imatinib. Only 10 months after the completion of adjuvant imatinib treatment, a computed tomography scan revealed gastrointestinal stromal tumor recurrence in this patient, with multiple peritoneal nodules in the upper abdomen being detected. Our patient was rechallenged with imatinib 400 mg/day and had a partial response after one month of treatment. Imatinib rechallenge was well tolerated by our patient; the only adverse events she experienced were grade 1 edema, anemia and fatigue. Our patient maintained a partial response two years and six months after the imatinib rechallenge. However, computed tomography scans three months later showed that our patient had disease progression. CONCLUSIONS: This case report demonstrates that a patient with a gastrointestinal stromal tumor who had previously received adjuvant imatinib therapy responded to imatinib rechallenge as treatment for her recurrent disease. These results indicate that imatinib sensitivity can be maintained in a patient with previous exposure to adjuvant imatinib therapy. PMID- 21975445 TI - Inhibition of the slow afterhyperpolarization restores the classical spike timing dependent plasticity rule obeyed in layer 2/3 pyramidal cells of the prefrontal cortex. AB - The induction of long-term potentiation (LTP) and long-term depression (LTD) of excitatory postsynaptic currents was investigated in proximal synapses of layer 2/3 pyramidal cells of the rat medial prefrontal cortex. The spike timing dependent plasticity (STDP) induction protocol of negative timing, with postsynaptic leading presynaptic stimulation of action potentials (APs), induced LTD as expected from the classical STDP rule. However, the positive STDP protocol of presynaptic leading postsynaptic stimulation of APs predominantly induced a presynaptically expressed LTD rather than the expected postsynaptically expressed LTP. Thus the induction of plasticity in layer 2/3 pyramidal cells does not obey the classical STDP rule for positive timing. This unusual STDP switched to a classical timing rule if the slow Ca(2+)-dependent, K(+)-mediated afterhyperpolarization (sAHP) was inhibited by the selective blocker N-trityl-3 pyridinemethanamine (UCL2077), by the beta-adrenergic receptor agonist isoproterenol, or by the cholinergic agonist carbachol. Thus we demonstrate that neuromodulators can affect synaptic plasticity by inhibition of the sAHP. These findings shed light on a fundamental question in the field of memory research regarding how environmental and behavioral stimuli influence LTP, thereby contributing to the modulation of memory. PMID- 21975444 TI - Prestin in HEK cells is an obligate tetramer. AB - The unusual membrane motor protein prestin is essential for mammalian hearing and for the survival of cochlear outer hair cells. While prestin has been demonstrated to be a homooligomer, by Western blot and FRET analyses, the stoichiometry of self association is unclear. Prestin, coupled to the enhanced green fluorescent protein, was synthesized and membrane targeted in human embryonic kidney cells by plasmid transfection. Fragments of membrane containing immobilized fluorescent molecules were isolated by osmotic lysis. Diffraction limited fluorescent spots consistent in size with single molecules were observed. Under continuous excitation, the spots bleached to background in sequential and approximately equal-amplitude steps. The average step count to background levels was 2.7. A binomial model of prestin oligomerization indicated that prestin was most likely a tetramer, and that a fraction of the green fluorescent protein molecules was dark. As a positive control, the same procedure was applied to cells transfected with plasmids coding for the human cyclic nucleotide-gated ion channel A3 subunit (again coupled to the enhanced green fluorescent protein), which is an obligate tetramer. The average step count for this molecule was also 2.7. This result implies that in cell membranes prestin oligomerizes to a tetramer. PMID- 21975446 TI - Cerebellar regions involved in adaptation to force field and visuomotor perturbation. AB - Studies with patients and functional magnetic resonance imaging investigations have demonstrated that the cerebellum plays an essential role in adaptation to visuomotor rotation and force field perturbation. To identify cerebellar structures involved in the two tasks, we studied 19 patients with focal lesions after cerebellar infarction. Focal lesions were manually traced on magnetic resonance images and normalized using a new spatially unbiased template of the cerebellum. In addition, we reanalyzed data from 14 patients with cerebellar degeneration using voxel-based morphometry. We found that adjacent regions with only little overlap in the anterior arm area (lobules IV to VI) are important for adaptation in both tasks. Although adaptation to the force field task lay more anteriorly (lobules IV and V), lobule VI was more important for the visuomotor task. In addition, regions in the posterolateral cerebellum (Crus I and II) contributed to both tasks. No consistent involvement of the posterior arm region (lobule VIII) was found. Independence of the two kinds of adaptation is further supported by findings that performance in one task did not correlate to performance in the other task. Our results show that the anterior arm area of the cerebellum is functionally divided into a more posterior part of lobule VI, extending into lobule V, related to visuomotor adaption, and a more anterior part including lobules IV and V, related to force field adaption. The posterolateral cerebellum may process common aspects of both tasks. PMID- 21975447 TI - Hierarchical control of motor units in voluntary contractions. AB - For the past five decades there has been wide acceptance of a relationship between the firing rate of motor units and the afterhyperpolarization of motoneurons. It has been promulgated that the higher-threshold, larger-soma, motoneurons fire faster than the lower-threshold, smaller-soma, motor units. This relationship was based on studies on anesthetized cats with electrically stimulated motoneurons. We questioned its applicability to motor unit control during voluntary contractions in humans. We found that during linearly force increasing contractions, firing rates increased as exponential functions. At any time and force level, including at recruitment, the firing rate values were inversely related to the recruitment threshold of the motor unit. The time constants of the exponential functions were directly related to the recruitment threshold. From the Henneman size principle it follows that the characteristics of the firing rates are also related to the size of the soma. The "firing rate spectrum" presents a beautifully simple control scheme in which, at any given time or force, the firing rate value of earlier-recruited motor units is greater than that of later-recruited motor units. This hierarchical control scheme describes a mechanism that provides an effective economy of force generation for the earlier-recruited lower force-twitch motor units, and reduces the fatigue of later-recruited higher force-twitch motor units-both characteristics being well suited for generating and sustaining force during the fight-or-flight response. PMID- 21975448 TI - Plantarflexor stretch training increases reciprocal inhibition measured during voluntary dorsiflexion. AB - Agonist-mediated reciprocal inhibition (RI) in distal skeletal muscles is an important neurophysiological phenomenon leading to improved movement coordination and efficiency. It has been shown to be reduced in aged and clinical populations, so the development of interventions augmenting RI is an important research goal. We examined the efficacy of using chronic passive muscle stretching to augment RI. The influence of 3 wk of plantarflexor stretching (4 * 30 s, two times/day) on RI of soleus and gastrocnemius initiated by tonic, voluntary dorsiflexion contractions [20% of maximum voluntary contraction (MVC)] was examined in 11 healthy men who performed stretch training and in nine nontraining controls. Hoffmann's reflexes (H-reflexes) were elicited by tibial nerve stimulation during both weak isometric (2% MVC) plantarflexions and dorsiflexion contractions at 20% MVC. Changes were examined at three joint angles, normalized to each subject's range of motion (ROM; plantarflexed = 10 +/- 0 degrees , neutral = -3.3 +/- 2.9 degrees , dorsiflexed = -16.5 +/- 5.6 degrees ). No changes were detected in controls. A 20% increase in ROM in the stretch subjects was associated with a significant decrease in maximum H-reflex (H(max)): maximum evoked potential (M(max)), measured during 2% plantarflexion at the plantarflexed and neutral angles in soleus and at the plantarflexed angle in gastrocnemius (P < 0.05-0.01). By contrast, decreases in H(max):M(max) during 20% dorsiflexion contract were also seen at each angle in soleus and at the dorsiflexed angle in gastrocnemius. However, a greater decrease in H(max):M(max) measured during voluntary dorsiflexion rather than during plantarflexion, which indicates a specific change in RI, was detected only at the dorsiflexed angle (-30.7 +/- 9.4% and -35.8 +/- 6.8% for soleus and gastrocnemius, respectively). These results demonstrate the efficacy of soleus-gastrocnemius stretch training in increasing agonist-mediated RI from tibialis anterior onto soleus-gastrocnemius in young, healthy individuals at dorsiflexed, but not plantarflexed, joint angles. PMID- 21975450 TI - Contribution of execution noise to arm movement variability in three-dimensional space. AB - Reaching movements are subject to noise associated with planning and execution, but precisely how these noise sources interact to determine patterns of endpoint variability in three-dimensional space is not well understood. For frontal plane movements, variability is largest along the depth axis (the axis along which visual planning noise is greatest), with execution noise contributing to this variability along the movement direction. Here we tested whether these noise sources interact in a similar way for movements directed in depth. Subjects performed sequences of two movements from a single starting position to targets that were either both contained within a frontal plane ("frontal sequences") or where the first was within the frontal plane and the second was directed in depth ("depth sequences"). For both sequence types, movements were performed with or without visual feedback of the hand. When visual feedback was available, endpoint distributions for frontal and depth sequences were generally anisotropic, with the principal axes of variability being strongly aligned with the depth axis. Without visual feedback, endpoint distributions for frontal sequences were relatively isotropic and movement direction dependent, while those for depth sequences were similar to those with visual feedback. Overall, the results suggest that in the presence of visual feedback, endpoint variability is dominated by uncertainty associated with planning and updating visually guided movements. In addition, the results suggest that without visual feedback, increased uncertainty in hand position estimation effectively unmasks the effect of execution-related noise, resulting in patterns of endpoint variability that are highly movement direction dependent. PMID- 21975449 TI - Assessing the role of inferior olivary sensory signaling in the expression of conditioned eyeblinks using a combined glutamate/GABAA receptor antagonist protocol. AB - The inferior olive (IO) is a major component of the eyeblink conditioning neural network. The cerebellar learning hypothesis assumes that the IO supplies the cerebellum with a "teaching" unconditioned stimulus input required for the acquisition of the conditioned response (CR) and predicts that inactivating this input leads to the extinction of CRs. Previous tests of this prediction attempted to block the teaching input by blocking glutamatergic sensory inputs in the IO. These tests were inconclusive because blocking glutamate neurotransmission in the IO produces a nonspecific tonic malfunction of cerebellar circuits. The purpose of the present experiment was to examine whether the behavioral outcomes of blocking glutamate receptors in the IO could be counterbalanced by reducing GABA mediated inhibition in the IO. We found that injecting the IO with the glutamate antagonist gamma-d-glutamylglycine (DGG) abolished previously learned CRs, whereas injecting the GABA(A) receptor antagonist gabazine at the same site did not affect CR incidence but shortened CR latencies and produced tonic eyelid closure. To test whether the glutamate antagonist-induced behavioral deficit could be offset by elevating IO activity with GABA(A) antagonists, rabbits were first injected with DGG and then with gabazine in the same training session. While DGG abolished CRs, follow-up injections of gabazine accelerated their recovery. These findings suggest that the level of IO neuronal activity is critical for the performance of CRs, and that combined pharmacological approaches that maintain spontaneous activity at near normal levels hold tremendous potential for unveiling the role of IO-mediated signals in eyeblink conditioning. PMID- 21975451 TI - Sensitivity to temporal modulation rate and spectral bandwidth in the human auditory system: MEG evidence. AB - Slow acoustic modulations below 20 Hz, of varying bandwidths, are dominant components of speech and many other natural sounds. The dynamic neural representations of these modulations are difficult to study through noninvasive neural-recording methods, however, because of the omnipresent background of slow neural oscillations throughout the brain. We recorded the auditory steady-state responses (aSSR) to slow amplitude modulations (AM) from 14 human subjects using magnetoencephalography. The responses to five AM rates (1.5, 3.5, 7.5, 15.5, and 31.5 Hz) and four types of carrier (pure tone and 1/3-, 2-, and 5-octave pink noise) were investigated. The phase-locked aSSR was detected reliably in all conditions. The response power generally decreases with increasing modulation rate, and the response latency is between 100 and 150 ms for all but the highest rates. Response properties depend only weakly on the bandwidth. Analysis of the complex-valued aSSR magnetic fields in the Fourier domain reveals several neural sources with different response phases. These neural sources of the aSSR, when approximated by a single equivalent current dipole (ECD), are distinct from and medial to the ECD location of the N1m response. These results demonstrate that the globally synchronized activity in the human auditory cortex is phase locked to slow temporal modulations below 30 Hz, and the neural sensitivity decreases with an increasing AM rate, with relative insensitivity to bandwidth. PMID- 21975452 TI - Neural coding of continuous speech in auditory cortex during monaural and dichotic listening. AB - The cortical representation of the acoustic features of continuous speech is the foundation of speech perception. In this study, noninvasive magnetoencephalography (MEG) recordings are obtained from human subjects actively listening to spoken narratives, in both simple and cocktail party-like auditory scenes. By modeling how acoustic features of speech are encoded in ongoing MEG activity as a spectrotemporal response function, we demonstrate that the slow temporal modulations of speech in a broad spectral region are represented bilaterally in auditory cortex by a phase-locked temporal code. For speech presented monaurally to either ear, this phase-locked response is always more faithful in the right hemisphere, but with a shorter latency in the hemisphere contralateral to the stimulated ear. When different spoken narratives are presented to each ear simultaneously (dichotic listening), the resulting cortical neural activity precisely encodes the acoustic features of both of the spoken narratives, but slightly weakened and delayed compared with the monaural response. Critically, the early sensory response to the attended speech is considerably stronger than that to the unattended speech, demonstrating top-down attentional gain control. This attentional gain is substantial even during the subjects' very first exposure to the speech mixture and therefore largely independent of knowledge of the speech content. Together, these findings characterize how the spectrotemporal features of speech are encoded in human auditory cortex and establish a single-trial-based paradigm to study the neural basis underlying the cocktail party phenomenon. PMID- 21975453 TI - Theta oscillations reflect a putative neural mechanism for human sensorimotor integration. AB - Hippocampal theta oscillations (3-12 Hz) may reflect a mechanism for sensorimotor integration in rats (Bland BH. Prog Neurobiol 26: 1-54, 1986); however, it is unknown whether cortical theta activity underlies sensorimotor integration in humans. Rather, the mu rhythm (8-12 Hz) is typically found to desynchronize during movement. We measured oscillatory EEG activity for two conditions of an instructed delayed reaching paradigm. Conditions 1 and 2 were designed to differentially manipulate the contribution of the ventral visuomotor stream during the response initiation phase. We tested the hypothesis that theta activity would reflect changes in the relevant sensorimotor network: condition 2 engaged ventral stream mechanisms to a greater extent than condition 1. Theta oscillations were more prevalent during movement initiation and execution than during periods of stillness, consistent with a sensorimotor relevance for theta activity. Furthermore, theta activity was more prevalent at temporal sites in condition 2 than condition 1 during response initiation, suggesting that theta activity is present within the necessary sensorimotor network. Mu activity desynchronized more during condition 2 than condition 1, suggesting mu desynchronization is also specific to the sensorimotor network. In summary, cortical theta synchronization and mu desynchronization may represent broadly applicable rhythmic mechanisms for sensorimotor integration in the human brain. PMID- 21975454 TI - Features of hand-foot crawling behavior in human adults. AB - Interlimb coordination of crawling kinematics in humans shares features with other primates and nonprimate quadrupeds, and it has been suggested that this is due to a similar organization of the locomotor pattern generators (CPGs). To extend the previous findings and to further explore the neural control of bipedal vs. quadrupedal locomotion, we used a crawling paradigm in which healthy adults crawled on their hands and feet at different speeds and at different surface inclinations (13 degrees , 27 degrees , and 35 degrees ). Ground reaction forces, limb kinematics, and electromyographic (EMG) activity from 26 upper and lower limb muscles on the right side of the body were collected. The EMG activity was mapped onto the spinal cord in approximate rostrocaudal locations of the motoneuron pools to characterize the general features of cervical and lumbosacral spinal cord activation. The spatiotemporal pattern of spinal cord activity significantly differed between quadrupedal and bipedal gaits. In addition, participants exhibited a large range of kinematic coordination styles (diagonal vs. lateral patterns), which is in contrast to the stereotypical kinematics of upright bipedal walking, suggesting flexible coupling of cervical and lumbosacral pattern generators. Results showed strikingly dissimilar directional horizontal forces for the arms and legs, considerably retracted average leg orientation, and substantially smaller sacral vs. lumbar motoneuron activity compared with quadrupedal gait in animals. A gradual transition to a more vertical body orientation (increasing the inclination of the treadmill) led to the appearance of more prominent sacral activity (related to activation of ankle plantar flexors), typical of bipedal walking. The findings highlight the reorganization and adaptation of CPG networks involved in the control of quadrupedal human locomotion and a high specialization of the musculoskeletal apparatus to specific gaits. PMID- 21975455 TI - The function of neuromuscular compartments in human shoulder muscles. AB - The aim of this study was to use a surface electromyographic (sEMG) technique with a ballistic isotonic shoulder joint adduction movement to determine the function of the neuromuscular compartments (NMCs) within the pectoralis major, deltoid, and latissimus dorsi muscles. Sixteen male subjects (mean age 22 yr) with no known history of shoulder pathologies volunteered to participate. Timing and intensity of muscle contraction, recorded with 15 pairs of bipolar sEMG electrodes, were compared during performance of 40 degrees coronal-plane ballistic [movement time (MT) < 400 ms] shoulder joint adduction movements. The results suggested that heterogeneous sEMG was present across the breadth of all three muscles, indicating the presence of individual NMCs with significant (P < 0.05) differences observed within the three muscles in NMC onset, duration, timing of peak NMC intensity, or relative intensity of NMC activation. For example, within the deltoid NMC activation was closely related to moment arm (MA) length with the NMC, with the largest antagonist MA deltoid NMC3 having a late period of activation [antagonist (Ant)] to slow glenohumeral joint (GHJ) rotation and maintain its final joint position [with agonist 2 burst (Ag2)]. The most obvious triphasic EMG patterns (e.g., Ag1-Ant-Ag2) were observed between the first NMCs activated in the two agonist muscles and the last NMC activated in the antagonist deltoid muscle. In conclusion, our findings suggest the presence of in parallel NMCs within the superficial muscles of the GHJ and show that biomechanical parameters, such as the MA at end-point movement position, influence the function of each NMC and its contribution to alternating patterns of agonist and antagonist muscle activity typical of ballistic movement. PMID- 21975457 TI - Decreased frontal plane hip joint moments in runners with excessive varus excursion at the knee. AB - Knee varus position and motion have been correlated with increased medial knee loading during gait. The purpose of this study is to determine whether runners with excessive varus excursion (EVE) at the knee demonstrate frontal plane knee and hip kinetics that are different from those of runners with normal varus excursion (NVE). Twelve runners with EVE were compared with 12 NVE subjects using three-dimensional kinematics and kinetics. Frontal plane angles and moments were compared at the knee and hip. Runners with EVE had significantly greater abductor moment of the knee (p = .004) and lower peak abductor moment of the hip (p = .047). Runners with EVE demonstrate knee and hip mechanics thought to be associated with increased medial tibiofemoral loading. Further understanding of how changing hip abductor moments may affect changes in knee abductor moments during running may potentially lead to interventions that augment long-term risk of injury. PMID- 21975458 TI - Production of stable aqueous dispersion of poly(3,4-ethylenedioxythiophene) nanorods using graphene oxide as a stabilizing agent and their application for nitrite detection. AB - A stable aqueous dispersion of poly(3,4-ethylenedioxythiophene) (PEDOT) nanorods stabilized by graphene oxide (GO) has been successfully prepared via interface polymerization of EDOT in the presence of GO for the first time. The non-covalent functionalization of PEDOT by GO leads to a PEDOT-GO dispersion that can be stable for several days without the observation of any floating or precipitated particles. Several analytical techniques including Raman spectroscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) have been used to characterize the resultant PEDOT-GO nanocomposites. It is found that such PEDOT-GO nanocomposites exhibit good catalytic activity toward the oxidation of nitrite, leading to a sensor for detection of nitrite. The linear detection range and detection limit are estimated to be 4 MUM to 2.48 mM (r = 0.999), and 1.2 MUM at a signal-to-noise ratio of 3, respectively. PMID- 21975456 TI - Nerve growth factor enhances the excitability of rat sensory neurons through activation of the atypical protein kinase C isoform, PKMzeta. AB - Our previous work showed that nerve growth factor (NGF) increased the excitability of small-diameter capsaicin-sensitive sensory neurons by activating the p75 neurotrophin receptor and releasing sphingolipid-derived second messengers. Whole cell patch-clamp recordings were used to establish the signaling pathways whereby NGF augments action potential (AP) firing (i.e., sensitization). Inhibition of MEK1/2 (PD-98059), PLC (U-73122, neomycin), or conventional/novel isoforms of PKC (bisindolylmaleimide I) had no effect on the sensitization produced by NGF. Pretreatment with a membrane-permeable, myristoylated pseudosubstrate inhibitor of atypical PKCs (aPKCs: PKMzeta, PKCzeta, and PKClambda/iota) blocked the NGF-induced increase in AP firing. Inhibitors of phosphatidylinositol 3-kinase (PI3K) also blocked the sensitization produced by NGF. Isolated sensory neurons were also treated with small interfering RNA (siRNA) targeted to PKCzeta. Both Western blots and quantitative real-time PCR established that PKMzeta, but neither full-length PKCzeta nor PKClambda/iota, was significantly reduced after siRNA exposure. Treatment with these labeled siRNA prevented the NGF-induced enhancement of excitability. Furthermore, consistent with the high degree of catalytic homology for aPKCs, internal perfusion with active recombinant PKCzeta or PKCiota augmented excitability, recapitulating the sensitization produced by NGF. Internal perfusion with recombinant PKCzeta suppressed the total potassium current and enhanced the tetrodotoxin-resistant sodium current. Pretreatment with the myristoylated pseudosubstrate inhibitor blocked the increased excitability produced by ceramide or internal perfusion with recombinant PKCzeta. These results demonstrate that NGF leads to the activation of PKMzeta that ultimately enhances the capacity of small-diameter capsaicin-sensitive sensory neurons to fire APs through a PI3K-dependent signaling cascade. PMID- 21975459 TI - Kinematic and kinetic synergies of the lower extremities during the pull in olympic weightlifting. AB - The purpose of this study was to identify multijoint lower extremity kinematic and kinetic synergies in weightlifting and compare these synergies between joints and across different external loads. Subjects completed sets of the clean exercise at loads equal to 65, 75, and 85% of their estimated 1-RM. Functional data analysis was used to extract principal component functions (PCF's) for hip, knee, and ankle joint angles and moments of force during the pull phase of the clean at all loads. The PCF scores were then compared between joints and across loads to determine how much of each PCF was present at each joint and how it differed across loads. The analyses extracted two kinematic and four kinetic PCF's. The statistical comparisons indicated that all kinematic and two of the four kinetic PCF's did not differ across load, but scaled according to joint function. The PCF's captured a set of joint- and load-specific synergies that quantified biomechanical function of the lower extremity during Olympic weightlifting and revealed important technical characteristics that should be considered in sports training and future research. PMID- 21975460 TI - Repairing critical-sized calvarial defects with BMSCs modified by a constitutively active form of hypoxia-inducible factor-1alpha and a phosphate cement scaffold. AB - Tissue engineering combined with gene therapy represents a promising approach for bone regeneration. The Hypoxia-inducible factor-1alpha (HIF-1alpha) gene is a pivotal regulator of vascular reactivity and angiogenesis. Our recent study has showed that HIF-1alpha could promote osteogenesis of bone mesenchymal stem cells (BMSCs) using a gene point mutant technique. To optimize the function of HIF 1alpha on inducing stem cells, another constitutively active form of HIF-1alpha (CA5) was constructed with truncation mutant method and its therapeutic potential on critical-sized bone defects was evaluated with calcium-magnesium phosphate cement (CMPC) scaffold in a rat model. BMSCs were treated with Lenti (lentivirus) -CA5, Lenti-WT (wild-type HIF-1alpha), and Lenti-LacZ. These genetically modified BMSCs were then combined with CMPC scaffolds to repair critical-sized calvarial defects in rats. The results showed that the overexpression of HIF-1alpha obviously enhanced the mRNA and protein expression of osteogenic markers in vitro and robust new bone formation with the higher local bone mineral density (BMD) was found in vivo in the CA5 and WT groups. Furthermore, CA5 showed significantly greater stability and osteogenic activity in BMSCs compared with WT. These data suggest that BMSCs transduced with truncation mutanted HIF-1alpha gene can promote the overexpression of osteogenic markers. CMPC could serve as a potential substrate for HIF-1alpha gene modified tissue engineered bone to repair critical sized bony defects. PMID- 21975461 TI - Thermosensitive/magnetic poly(organophosphazene) hydrogel as a long-term magnetic resonance contrast platform. AB - A thermosensitive/magnetic poly(organophosphazene) hydrogel (a magnetic hydrogel) was designed and synthesized for long-term magnetic resonance (MR) imaging. To turn a thermosensitive poly(organophosphazene) hydrogel (an original hydrogel) into a long-term MR contrast platform, cobalt ferrite (CoFe(2)O(4)) nanoparticles, which have hydrophobic surfaces, were bound to the original hydrogel via interactions between the hydrophobic surfaces of the nanoparticles and the (L)-isoleucine ethyl esters of the polymer. The magnetic hydrogel showed extremely low cytotoxicity and adequate magnetic properties for use in long-term MR imaging, in addition to possessing the same properties of the original hydrogel, such as viscosity, thermosensitivity, biodegradability, biocompatibility, a reversible sol-to-gel phase transition near body temperature, and injectability. The magnetic hydrogel was injected into a rat brain using stereotactic surgery. After the injection, the applicable potentiality as a long term MR contrast platform was successfully estimated over 4-5 weeks. Consequently, it was shown that a magnetic hydrogel as a long-term MR contrast platform has the potential to be applied in a long-term theranostic hydrogel system. Furthermore, it is expected that this platform can be useful in the clinical field of incurable diseases due to either surgical difficulties or lethality, such as with brain tumors, when the platform is combined with therapeutic drugs for long-term MR theragnosis in further studies. PMID- 21975462 TI - Low-density lipoprotein receptor gene transfer in hypercholesterolemic mice improves cardiac function after myocardial infarction. AB - Left ventricular (LV) function post-myocardial infarction (MI) is adversely influenced by hypercholesterolemia independent of the severity of coronary atherosclerosis. The objective of this study was to evaluate whether lipid lowering by adenoviral low-density lipoprotein (LDL) receptor (AdLDLr) gene transfer in C57BL/6 LDL receptor (LDLr)-deficient mice beneficially affects ventricular remodeling and cardiac function post-MI independent of effects on the coronary circulation. AdLDLr transfer reduced plasma cholesterol by 77% (P<0.0001). Survival 28 days post-MI was higher in AdLDLr-treated mice (95%) compared with control mice (80%) (P<0.05) (hazard ratio for mortality 0.26, 95% confidence interval 0.11-0.84). Infarct size was not significantly different at day 1 and day 7 but was reduced by 18% (P<0.05) at day 28 in AdLDLr MI mice compared with control MI mice. Cardiomyocyte hypertrophy and interstitial fibrosis were reduced and neovascularization was increased in AdLDLr MI mice. LDLr gene transfer had beneficial effects on endothelial progenitor cell (EPC) number and ex vivo EPC function. LV contractility and relaxation were better preserved in AdLDLr MI mice compared with control MI mice. In conclusion, lipid lowering in hypercholesterolemic mice exerts direct cardioprotective effects resulting in enhanced survival, reduced infarct size, decreased ventricular remodeling and better cardiac function. PMID- 21975463 TI - MicroRNA-150-regulated vectors allow lymphocyte-sparing transgene expression in hematopoietic gene therapy. AB - Endogenous microRNA (miRNA) expression can be exploited for cell type-specific transgene expression as the addition of miRNA target sequences to transgenic cDNA allows for transgene downregulation specifically in cells expressing the respective miRNAs. Here, we have investigated the potential of miRNA-150 target sequences to specifically suppress gene expression in lymphocytes and thereby prevent transgene-induced lymphotoxicity. Abundance of miRNA-150 expression specifically in differentiated B and T cells was confirmed by quantitative reverse transcriptase PCR. Mono- and bicistronic lentiviral vectors were used to investigate the effect of miRNA-150 target sequences on transgene expression in the lymphohematopoietic system. After in vitro studies demonstrated effective downregulation of transgene expression in murine B220(+) B and CD3(+) T cells, the concept was further verified in a murine transplant model. Again, marked suppression of transgene activity was observed in B220(+) B and CD4(+) or CD8(+) T cells whereas expression in CD11b(+) myeloid cells, lin(-) and lin(-)/Sca1(+) progenitors, or lin(-)/Sca1(+)/c-kit(+) stem cells remained almost unaffected. No toxicity of miRNA-150 targeting in transduced lymphohematopoietic cells was noted. Thus, our results demonstrate the suitability of miRNA-150 targeting to specifically suppress transgene expression in lymphocytes and further support the concept of miRNA targeting for cell type-specific transgene expression in gene therapy approaches. PMID- 21975464 TI - The oncolytic adenovirus AdDeltaDelta enhances selective cancer cell killing in combination with DNA-damaging drugs in pancreatic cancer models. AB - Pancreatic adenocarcinomas are aggressive and frequently develop resistance to all current therapies. Replication-selective adenoviruses can overcome resistance to chemotherapeutics through their sensitizing effects on drug-induced cell killing. We previously found that adenovirus deleted in the anti-apoptotic E1B19K gene enhanced gemcitabine-induced apoptotis. Here we demonstrate that our engineered double-deleted AdDeltaDelta mutant (deleted in the pRb-binding E1ACR2 region and E1B19K) selectively replicates and enhances cell killing in combination with DNA-damaging cytotoxic drugs in pancreatic cancer cells. Combinations of AdDeltaDelta with gemcitabine, irinotecan or cisplatin resulted in two- to fourfold decreases in EC(50) (half maximal effective concentration) values and was more efficent than similar combinations with wild-type virus, the dl1520 (ONYX-015) and dl922-947 mutants. AdDeltaDelta replication was impaired in normal bronchial human epithelial cells and did not sensitize the cells to drugs. Gemcitabine-insensitive AsPC-1, BxPC-3 and PANC-1 cells were efficiently killed by irinotecan in combination with AdDeltaDelta. Suboptimal doses of AdDeltaDelta and gemcitabine significantly prolonged time to tumor progression in two human pancreatic tumor xenograft in vivo models, PT45 and SUIT-2. We conclude that AdDeltaDelta has low toxicity to normal cells while potently sensitizing pancreatic cancer cells to DNA-damaging drugs, and holds promise as an improved therapeutic strategy for pancreatic cancer. PMID- 21975465 TI - Novel Clostridium perfringens enterotoxin suicide gene therapy for selective treatment of claudin-3- and -4-overexpressing tumors. AB - Bacterial toxins are known to be effective for cancer therapy. Clostridium perfringens enterotoxin (CPE) is produced by the bacterial Clostridium type A strain. The transmembrane proteins claudin-3 and -4, often overexpressed in numerous human epithelial tumors (for example, colon, breast, pancreas, prostate and ovarian), are the targeted receptors for CPE. CPE binding to them triggers formation of membrane pore complexes leading to rapid cell death. In this study, we aimed at selective tumor cell killing by CPE gene transfer. We generated expression vectors bearing the bacterial wild-type CPE cDNA (wtCPE) or translation-optimized CPE (optCPE) cDNA for in vitro and in vivo gene therapy of claudin-3- and -4-overexpressing tumors. The CPE expression analysis at messenger RNA and protein level revealed more efficient expression of optCPE compared with wtCPE. Expression of optCPE showed rapid cytotoxic activity, hightened by CPE release as bystander effect. Cytotoxicity of up to 100% was observed 72 h after gene transfer and is restricted to claudin-3-and -4-expressing tumor lines. MCF-7 and HCT116 cells with high claudin-4 expression showed dramatic sensitivity toward CPE toxicity. The claudin-negative melanoma line SKMel-5, however, was insensitive toward CPE gene transfer. The non-viral intratumoral in vivo gene transfer of optCPE led to reduced tumor growth in MCF-7 and HCT116 tumor-bearing mice compared with the vector-transfected control groups. This novel approach demonstrates that CPE gene transfer can be employed for a targeted suicide gene therapy of claudin-3- and -4-overexpressing tumors, leading to the rapid and efficient tumor cell killing in vitro and in vivo. PMID- 21975466 TI - Gene therapy for retinal ganglion cell neuroprotection in glaucoma. AB - Glaucoma is the leading cause of irreversible blindness worldwide. The primary cause of glaucoma is not known, but several risk factors have been identified, including elevated intraocular pressure and age. Loss of vision in glaucoma is caused by the death of retinal ganglion cells (RGCs), the neurons that convey visual information from the retina to the brain. Therapeutic strategies aimed at delaying or halting RGC loss, known as neuroprotection, would be valuable to save vision in glaucoma. In this review, we discuss the significant progress that has been made in the use of gene therapy to understand mechanisms underlying RGC degeneration and to promote the survival of these neurons in experimental models of optic nerve injury. PMID- 21975467 TI - A pilot cluster randomized controlled trial of structured goal-setting following stroke. AB - OBJECTIVE: To determine the feasibility, the cluster design effect and the variance and minimal clinical importance difference in the primary outcome in a pilot study of a structured approach to goal-setting. DESIGN: A cluster randomized controlled trial. SETTING: Inpatient rehabilitation facilities. SUBJECTS: People who were admitted to inpatient rehabilitation following stroke who had sufficient cognition to engage in structured goal-setting and complete the primary outcome measure. INTERVENTIONS: Structured goal elicitation using the Canadian Occupational Performance Measure. MAIN MEASURES: Quality of life at 12 weeks using the Schedule for Individualised Quality of Life (SEIQOL-DW), Functional Independence Measure, Short Form 36 and Patient Perception of Rehabilitation (measuring satisfaction with rehabilitation). Assessors were blinded to the intervention. RESULTS: Four rehabilitation services and 41 patients were randomized. We found high values of the intraclass correlation for the outcome measures (ranging from 0.03 to 0.40) and high variance of the SEIQOL DW (SD 19.6) in relation to the minimally importance difference of 2.1, leading to impractically large sample size requirements for a cluster randomized design. CONCLUSIONS: A cluster randomized design is not a practical means of avoiding contamination effects in studies of inpatient rehabilitation goal-setting. Other techniques for coping with contamination effects are necessary. PMID- 21975468 TI - A four-week walking exercise programme in patients with knee osteoarthritis improves the ability of dual-task performance: a randomized controlled trial. AB - OBJECTIVE: To investigate whether a four-week walking exercise programme in patients with knee osteoarthritis improves the ability of dual-task performance in older adults with knee osteoarthritis. DESIGN: A randomized controlled trial with two groups: a walking group and a control group. SUBJECTS: Forty older adults with knee osteoarthritis, 20 participants in each group. INTERVENTION: The walking intervention was designed to increase the number of steps walked daily. The walking group was instructed to increase their number of steps to 3000 steps more than before the intervention. MAIN OUTCOME MEASURES: Dual-task performance was computed by an automaticity index: the walking velocity under single-task condition/under dual-task conditions * 100 (%), defined as automaticity. The nearer to 100% automaticity, the better the dual-task performance. Decrease of the Trail Making Test (TMT) performance was defined as DeltaTMT. DeltaTMT was calculated as the difference between times (part B-part A) as a measure of executive function. In addition, functional ability was measured by the Japanese Knee Osteoarthritis Measure. RESULTS: The walking group improved significantly in automaticity (P < 0.001, from 75.2 (7.6) to 86.9 (10.4), DeltaTMT (P < 0.001, from 63.4 (43.1) to 48.3 (29.6)) and Japanese Knee Osteoarthritis Measure score (P < 0.001, from 54.4 to 51.9) compared with before the intervention, while the control group displayed no significant differences. CONCLUSIONS: We found that walking exercise improves executive function and dual-task performance. PMID- 21975469 TI - A cost analysis of specialist inpatient neurorehabilitation services in the UK. AB - OBJECTIVE: To determine the range and variation in costs and service characteristics between different levels of specialist neurorehabilitation services in England, and to determine key predictors of service costs. DESIGN: A retrospective analysis of service costs, staffing and activity levels, with comparison across service types. SETTING: Specialist neurorehabilitation services (n = 17) from different areas of England, were divided into three types according to predefined criteria: adult level 1 (tertiary) (n = 8) and level 2a (supra district) (n = 7) services; and children's services (n = 2). MAIN MEASURES: Annual service costs were collated using a standard costing template, and divided according to principal cost type (direct/indirect/overheads) and behaviour (variable/non-variable). For comparison between the level 1 and 2a services, costs and service characteristics were calculated per occupied bed. RESULTS: The percentage breakdown of costs was consistent across all three service types, with direct costs making up 83%, indirect 10%, and overheads 7% of total costs. The median variable component ranged from 75 to 76%. Staff pay made up 66% and accounted for 95% of the variance of the total costs in adult services. Level 1 services had higher total staffing costs, mainly reflecting higher therapy staff numbers (z = -2.0, P = 0.05). The median total costs/bed-day were: level 1 L530 (interquartile range (IQR) 435-574) (equivalent to US$860 or ?650) and level 2a L402 (US$650 or ?459) (IQR 326-451) (z = -2.5, P = 0.009). Children's services cost almost twice that (L1017-1177). CONCLUSIONS: Expected variations in cost are largely due to differences in staff costs. Total staff costs projected by 150% provided a reasonable estimate of total unit costs. PMID- 21975470 TI - Systematic back muscle exercise after percutaneous vertebroplasty for spinal osteoporotic compression fracture patients: a randomized controlled trial. AB - OBJECTIVE: To analyze the clinical significance of postoperative back muscle exercises after percutaneous vertebroplasty for spinal osteoporotic compression fracture patients. DESIGN: Clinical randomized controlled trials of parallel group nonpharmacologic study. SETTING: Patients practised back muscle exercises in the spinal surgery department, rehabilitation department and at their residences. SUBJECTS: Osteoporotic compression fracture patients who had undergone percutaneous vertebroplasty and processed sufficient muscle strength to participate in the training were studied. INTERVENTIONS: Patients were randomized into two groups, which were titled A and B. General postoperation therapy, including antiosteoporotic medications and education, was offered to all patients. Group B patients received additional systematic back muscle exercise. MAIN MEASURES: Both Oswestry Disability Index (ODI) and visual analogue scale (VAS) were recorded preoperatively and postoperatively at three-day, one-month, six-month, one-year and two-year follow-up. RESULTS: From January 2006 to January 2009, a total of 82 patients were assessed for eligibility, 60 patients were enrolled and randomized into two groups. Forty-two (70%) patients (20 of 30 in Group A and 22 of 30 in Group B) were successfully followed-up for two years. Systematic back muscle exercises resulted in a significant advantage in both measurements. The ODI of Group B was significantly better than Group A at the six month, one-year and two-year follow-ups (P < 0.05). The pain level of Group B was significantly lower than in Group A at the one- and two-year follow-ups (P < 0.05). At the end of our study, the mean (SD) of the ODI in Groups A and B were 39.1 (9.14) and 23.4 (5.62); the mean (SD) of the VAS in Groups A and B were 3.4 (1.15) and 2.1 (0.84), respectively. CONCLUSIONS: Our findings suggest that the benefit of the exercises required at least six months to be observed; however, the favourable effects could last for two years. Therefore, systematic back muscle exercise should be recommended as one of the treatment guidelines for postpercutaneous vertebroplasty patients. PMID- 21975472 TI - A prospective comparison of two commercial mesh kits in the management of anterior vaginal prolapse. AB - INTRODUCTION AND HYPOTHESIS: Vaginal mesh kits are increasingly used in the management of pelvic organ prolapse. This study aimed to determine similarity of outcomes of the Anterior Prolift with Perigee systems for anterior compartment prolapse. METHODS: Consecutive women undergoing Perigee or Anterior Prolift for symptomatic stage 2 or greater anterior vaginal prolapse were prospectively evaluated. Main outcome measures included objective and subjective success rates, perioperative outcomes, patient satisfaction, and complications. RESULTS: One hundred and six women (Prolift, 52; Perigee, 54) completed questionnaires, and 91 (Prolift, 46; Perigee, 45) were examined postoperatively. At follow-up (Prolift: median, 11.0; range, 5-23 months; Perigee: median, 11.5; range, 6 - 23 months), objective success rates (Prolift, 89%; Perigee, 80%; p = 0.23), subjective success rates (Prolift, 94%; Perigee, 96%; p=0.62), mean +/- SD patient satisfaction (Prolift, 8.2 +/- 2.0; Perigee, 8.2 +/- 1.8; p = 0.91), and complication rates did not differ significantly between the two groups. CONCLUSIONS: The Anterior Prolift was found to not differ significantly from Perigee at 11 months. PMID- 21975473 TI - Full-color InGaN/GaN dot-in-a-wire light emitting diodes on silicon. AB - We report on the achievement of a new class of nanowire light emitting diodes (LEDs), incorporating InGaN/GaN dot-in-a-wire nanoscale heterostructures grown directly on Si(111) substrates. Strong emission across nearly the entire visible wavelength range can be realized by varying the dot composition. Moreover, we have demonstrated phosphor-free white LEDs by controlling the indium content in the dots in a single epitaxial growth step. Such devices can exhibit relatively high internal quantum efficiency (>20%) and no apparent efficiency droop for current densities up to ~ 200 A cm(-2). PMID- 21975474 TI - Callista Roy's adaptation model. PMID- 21975475 TI - The power of theoretical knowledge. AB - Nursing theoretical knowledge has demonstrated powerful contributions to education, research, administration and professional practice for guiding nursing thought and action. That knowledge has shifted the primary focus of the nurse from nursing functions to the person. Theoretical views of the person raise new questions, create new approaches and instruments for nursing research, and expand nursing scholarship throughout the world. PMID- 21975476 TI - Conceptual development of an instrument to measure the internalized stigma of AIDS based on the Roy adaptation model. AB - In this column the author describes the development of an instrument to measure internalized stigma of HIV/AIDS based on the self-concept adaptive mode of the Roy adaptation model. The Internalized Stigma of AIDS Tool is a 10-item instrument that is derived from the physical self (body sensation and image) and personal self (self-consistency, self-ideal and moral-ethical-spiritual self) as set forth by Roy. An overview of the Roy adaptation model and the theory of the person as an adaptive system illustrates how this instrument was derived. PMID- 21975477 TI - Angst for nursing theory. PMID- 21975478 TI - Research based on the Roy adaptation model: last 25 years. AB - Two key events lead to the prominence of links among Roy's grand theory, derived middle-range theories and the design of research. The author in this column describes this work in two formats. Essential details of two areas of research are presented in episodic form-the first is work on secondary analysis of Roy model-based research over 40 years and the author's study of persons' cognitive recovery from mild head injury. The second is a project on re-conceptualizing coping and adaptation processing in sequential detail within the context of work in the field and the significance of on-going work for nursing practice. PMID- 21975479 TI - Reading between the lines: a leading-following phenomenon. AB - The climate of contemporary healthcare is chaotic and in constant change. University faculty members receive incessant societal calls to better educate and graduate greater numbers of nurse leaders. Healthcare literature is replete with discussions of the desired qualities of successful leaders. In this column, readers are invited to reflect upon potential meanings for holding up the mirror and for the metaphor of reading between the lines from a humanbecoming theoretical perspective in leading-following situations. PMID- 21975480 TI - What Is Not Yet: cultivating the imagination. AB - In this column, the author describes imaginative capacities that encourage imaginative thinking and creating anew. Concepts from the nursing theory of humanbecoming are presented to further explore the applicability of focusing on cultivating the imagination in nursing curricula. A nursing seminar is proposed, entitled What Is Not Yet, that could foster the creative potential of nurse leaders. PMID- 21975481 TI - Analyze this... PMID- 21975482 TI - Phenomenon development from practice to research. AB - One of the most prudent and efficient ways of conquering the task of developing new knowledge, is the utilization of practice to find phenomena. The purpose of this column is to present the construction of a phenomenon to be utilized for future study and explication utilizing this format. New nursing knowledge was developed by constructing a practice situation, identifying a phenomenon of interest, grounding the phenomenon in the focus of the discipline, and defining concepts related to the phenomenon. Through this evolutionary process one is able to identify a phenomenon to focus on, apply it to a particular population, ground it in theory, and lastly develop it into the foundation of future research. PMID- 21975483 TI - Extending the Roy adaptation model to meet changing global needs. AB - The purpose of this article is to articulate how the Roy adaptation model has been extended as a conceptual framework to meet changing global needs. Nursing's social mandate is described within the significant global changes of this century. The required synthesis of the individual and common good is predicated within the thinking of the model. Changes are described with specific examples of groups from the family to global society levels. The implications of this work for knowledge development are identified. PMID- 21975484 TI - Women's perceptions of caesarean birth: a Roy international study. AB - The purpose of this Roy adaptation model-based multi-site international mixed method study was to examine the relations of type of caesarean birth (unplanned/planned), number of caesarean births (primary/repeat), and preparation for caesarean birth to women's perceptions of and responses to caesarean birth. The sample included 488 women from the United States (n = 253), Finland (n = 213), and Australia (n = 22). Path analysis revealed direct effects for type of and preparation for caesarean birth on responses to caesarean birth, and an indirect effect for preparation on responses to caesarean birth through perception of birth the experience. PMID- 21975485 TI - Using the Roy adaptation model to develop an antenatal assessment instrument. AB - The utility of a nursing model as a framework to understand and explain a health phenomenon is fundamental to guide nursing practice. In this article, the authors aim to provide an examination of the Roy adaptation model as a basis for the development of an instrument used for assessing the health needs of pregnant women. With the congruence between the concepts in the Roy adaptation model and antenatal practice, an antenatal assessment instrument is developed. The assessment areas focus on pregnant women's behaviors in the four adaptation modes. The current experience is valuable for nurses who are involved in instrument development and midwifery practice. PMID- 21975486 TI - Toward development of a middle-range theory of psychological adaptation in death and dying. AB - This paper presents a middle-range theory of psychological adaptation in death and dying that was abstracted from a series of quantitative and qualitative studies. The findings from these studies are described, a conceptual definition for end-of-life psychological adaptation is given, evidence is synthesized into a limited number of assumptions, testable hypotheses are derived, and the constructed middle-range theory is linked to the conceptual-theoretical framework of the Roy adaptation model. PMID- 21975487 TI - Thai nurses' experience of caring for persons who had a peaceful death in intensive care units. AB - This phenomenological study describes the lived experience of caring for persons who had a peaceful death in the intensive care units. Ten intensive care nurses in south Thailand participated in individual interviews. Van Manen's approach was utilized to synthesize data. The lived experience of Thai nurses caring for persons who had a peaceful death is: understanding the other through valuing experience and enhancing relationships with others by recognizing time is short and is a priority. Boykin and Schoenhofer's theory of nursing as caring provided the theoretical lens for interpreting the meaning of the phenomenon. PMID- 21975488 TI - Lessons for nursing from the Lakota. PMID- 21975489 TI - The beauty of the moment: Lakota and humanbecoming perspective of time. AB - Time is an enigmatic concept, that despite considerable attention by philosophers and scientists, remains poorly understood by nurses. After a brief discussion of the general literature on time, the author discusses Parse's humanbecoming school of thought and the Lakota Native American view of time and related concepts. Implications for nursing are discussed. PMID- 21975490 TI - A legacy of leadership in nursing. AB - This introduces the guest author's column on perspectives on leadership developed through a career as a nurse leader. Parse's essentials of leadership: commitment to a vision, willingness to risk, and reverence for others, are noted in tributes from other leaders and followers, which point to the rich legacy of a distinguished career. PMID- 21975491 TI - Perspectives on leadership: moving out of the corner of our room. AB - Perspectives on leadership developed through a career as a nurse leader are shared, including the author's guiding vision, a valuing of nursing as knowledge work, how to create a learning organization that supports professional practice, and other lessons learned through experience. Readers are urged to find the leadership voice within, be courageous, engage surrounding opportunities, and be guided by their vision of what nursing should be in the future. PMID- 21975492 TI - Nursing Science Quarterly Best Paper Award 2010. PMID- 21975493 TI - Tibial plateau levelling osteotomy implant removal: a retrospective analysis of 129 cases. AB - OBJECTIVE: To evaluate a cohort of dogs undergoing tibial plateau levelling osteotomy (TPLO) implant removal to determine key clinical features, prevalence, and indications for implant removal. METHODS: Medical records of dogs undergoing TPLO implant removal at a private referral practice (Dallas Veterinary Surgical Center) between 2004-2008 were reviewed. Patient signalment, implant type, presence of concurrent medical disease, surgeon, antibiotic use, aerobic bacterial culture result, and operative findings were recorded. Data were analyzed using paired t-test, Fisher's exact test, and Wilcoxon-rank sum test. Statistical significance was set at p <0.05. RESULTS: The TPLO implants were removed from 126 dogs (n = 129, 4.8% of TPLO procedures) during the study period. Average time interval from TPLO to implant removal was 16.0 +/- 17.8 months. The most common clinical signs were the presence of an open wound (n = 80), draining tract (n = 64), and lameness (n = 59). Culture of tissue or fluid from the implant bed or implants was positive for bacterial growth in 95/115 cases. A significantly greater proportion of the implants removed were Slocum TPLO plates (n = 109; 6.1%) when compared to other TPLO plate types (n = 20; 2.3%) (p <0.0001). No association was identified between a positive bacterial culture and measured variables. CLINICAL SIGNIFICANCE: Local bacterial infection and clinical signs of inflammation were the most common reasons for TPLO implant removal. There may be an increased implant-associated complication rate for Slocum TPLO plates in the study population. PMID- 21975494 TI - Pyrilamine-induced prolonged QT interval in adolescent with drug overdose. AB - The widespread availability of antihistamines in many over-the-counter preparations can lead to significant hazard to the public because of their possible link to potential ventricular arrhythmias secondary to prolongation of QT interval. The effect can be further compounded by the use of other commonly used medications such as macrolides, antifungal agents, antipsychotics, and other antihistamine-containing preparations. The effect of antihistamines on QT interval is not a class effect but is unique to certain medications. Pyrilamine, a first-generation antihistaminic agent, is considered safe as there are no reports regarding its cardiac toxicity available in literature. We report a case of an adolescent with prolonged QT interval after an overdose of pyrilamine. PMID- 21975495 TI - Acute macroglossia in the pediatric patient: worth a look. AB - Macroglossia is defined as an enlarged tongue that in the resting position protrudes beyond the alveolar ridge or teeth. Macroglossia may be a chronic, indolent phenomenon or may be acute. We present a case of acute traumatic macroglossia in a pediatric patient following accidental self-application of an orthodontic elastic band. The 5-year-old patient presented with swelling of the anterior portion of the tongue unassociated with upper airway obstruction. The diagnosis was delayed until the patient was in the operating room under general anesthesia for repair of a presumed traumatic laceration, 3 weeks after her initial presentation. A thorough history may not reveal the cause of acute macroglossia. Examination under sedation may be necessary to establish a definitive diagnosis. PMID- 21975496 TI - Bacterial tracheitis: a varied entity. AB - OBJECTIVE: The objective of the study was to highlight the different presentations of bacterial tracheitis (BT), a potential life-threatening cause of airway obstruction in children. DESIGN: Case series. METHODS: A review of medical records of 4 cases of BT who presented with differing signs and symptoms was performed. RESULTS: Clinical manifestations of 4 patients with BT are presented with corresponding endoscopic appearances of the airway. Two patients were afebrile and nontoxic, and 2 had an elevated white cell count. Three had different degrees of stridor. One had a respiratory arrest. Cultures grew Staphylococcus aureus in 2 and Moraxella catarrhalis in 1 and were mixed in 1 patient. None required intubation. All were successfully treated with antibiotics and bronchoscopic debridement of the membranes. CONCLUSIONS: Bacterial tracheitis needs a high index of suspicion because of its varied presentations. Certain forms have less severe clinical manifestations. These forms also require aggressive management as they can result in airway obstruction from membranes and edema. PMID- 21975497 TI - Nausea, vomiting, and diarrhea in a 9-year-old girl. AB - Cryptosporidiosis is reported in an otherwise healthy child. Her history was significant for playing in natural waters during a camping trip 1 week prior. Several days later, she began improving despite an incorrect diagnosis and inappropriate antibiotic therapy. Nitazoxanide was given once the diagnosis was established. Obtaining a thorough patient history, administering appropriate antibiotics, and counseling patients on preventive measures are critical steps in treating and managing the transmission of this parasite. The case emphasizes the value of stool ova and parasite examination for proper diagnosis of pediatric diarrheal illness in the emergency setting. In addition, the often overlooked diagnosis of cryptosporidiosis is reviewed as an important cause of diarrheal illness in the immunocompetent pediatric population. PMID- 21975498 TI - Neurogenic pulmonary edema associated with pediatric status epilepticus. AB - Neurogenic pulmonary edema (NPE) can result from various central nervous system disorders such as brain malignancies, traumatic brain injuries, infections, and seizures. Although the pathogenesis is not completely understood, NPE creates an increase in pulmonary interstitial and alveolar fluid. In adults, it has been reported with prolonged seizure activity. In pediatric patients, pulmonary edema has rarely been reported after status epilepticus, and respiratory compromise is most often due to anticonvulsant-related respiratory depression. Treatment for NPE is largely supportive. If unrecognized, it can lead to hypoxia and respiratory arrest. We report a case of status epilepticus-related pulmonary edema in a female toddler, the youngest patient to be reported in the literature. PMID- 21975499 TI - Neisseria sicca endocarditis requiring mitral valve replacement in a previously healthy adolescent. AB - Infective endocarditis due to Neisseria sicca, a normal inhabitant of the upper respiratory tract, is rarely reported but associated with embolic phenomena and large vegetations often requiring surgical intervention. We report a previously healthy 12-year-old girl who presented with prolonged fever and altered mental status. The patient developed rapidly progressive respiratory insufficiency and cardiovascular instability, and echocardiography demonstrated a large vegetation on the mitral valve. She developed worsening mitral regurgitation with resultant pulmonary hemorrhage and underwent mitral valve replacement. Her blood culture was positive for N. sicca. This infection should be considered in patients with prolonged high fever and multiorgan dysfunction. Despite a typically severe course, reported mortality is low. PMID- 21975500 TI - Acute liver failure, autoimmune hepatitis, and leptospirosis: a case report. AB - The etiology of acute liver failure varies widely in children, but the most common causes are viral hepatitis, drugs, and toxins. We report herein a case of autoimmune hepatitis and acute liver failure caused by leptospirosis, which is involved rarely in etiology. PMID- 21975501 TI - The role of imaging studies for evaluation of stroke in children. AB - Stroke is a major cause of morbidity and mortality in children and long-term neurological deficits. Although cerebrovascular disorders occur less often in children than in adults, recognition of stroke in children has probably increased because of the widespread application of noninvasive diagnostic studies such as magnetic resonance imaging and computed tomography.Computed tomography (CT) should be the first imaging choice in the emergency setting when stroke is suspected. It will show the presence of hemorrhage (eg, bleeding from arteriovenous malformation). It is often normal within the first hours in arterial ischemic stroke. As in adults, magnetic resonance imaging is the neuroimaging modality to confirm the clinical diagnosis of ischemic stroke. In children, however, magnetic resonance imaging requires sedation and may not be as readily available as CT. Perfusion imaging demonstrates flow within the brain and can detect areas that are at risk of ischemia; however, further studies in the pediatric population need to be validated for this technique in children. Angiography detects arterial disease (eg, aneurysm); however, its use has been largely superseded by better magnetic resonance angiography, which is sensitive enough to visualize lesions in the proximal anterior cerebral artery, middle cerebral artery, and distal internal carotid artery (ICA). Magnetic resonance imaging using diffusion- weighted imaging is the most versatile and sensitive imaging technique for identifying ischemic lesions. In the future, we need to identify the pediatric patient presenting to the emergency department with an acute stroke and develop a pathway for the use of particular imaging techniques (eg, CT vs magnetic resonance imaging). PMID- 21975503 TI - Iron poisoning: a literature-based review of epidemiology, diagnosis, and management. AB - Although seen less frequently than acetaminophen or salicylate poisoning, acute iron poisoning remains a dangerous threat, particularly to pediatric patients. Multiple factors-including legal and manufacturing practices-have changed the landscape of iron poisoning over the decades. Despite these changes, diagnosis and management of iron poisoning have minimally evolved, and the current evidence for iron poisoning is yet based principally on case series, expert consensus, animal studies, and adult volunteer studies. This review article describes in detail the epidemiology of acute iron poisoning as it relates to the pediatric patient, as well as the historical and current array of literature on diagnosis and management. PMID- 21975504 TI - Use of emergency ultrasound in the diagnostic evaluation of an infant with vomiting. AB - The use of bedside emergency ultrasound in pediatric abdominal emergencies is becoming more widespread and can be a useful adjunct in the assessment of children who present with abdominal pain. Our case describes an infant who presented to the emergency department with vomiting, in whom an emergency ultrasound evaluation led to timely diagnosis and intervention of an unanticipated condition. PMID- 21975505 TI - ECGs in the ED. PMID- 21975506 TI - Pediatric emergency medicine: legal briefs. PMID- 21975508 TI - C-Reactive protein-directed immobilization of phosphocholine ligands on a solid surface. AB - The complexes of C-reactive protein (CRP) with its polymerizable phosphocholine ligands adsorbed at the styrene-water interface were polymerized. The molecularly imprinted polymer (MIP) exhibited a binding affinity for CRP comparable to that of immobilized anti-CRP antibody. The determination of human serum CRP using the MIP-based sandwich immunoassay has been demonstrated. PMID- 21975509 TI - Robotic-assisted reconstructive urology. AB - PURPOSE OF REVIEW: The use of robotic surgery in reconstructive urology has steadily increased since the year 2000. Articles in the MEDLINE database (from January 2000 to May 2011) identified using the Boolean search: robotic or robot assisted and reconstructive surgery and urology. In addition, the reference lists of previously published articles on robotic-assisted reconstructive surgery were checked for additional studies. This review will summarize the current advances in robotic-assisted reconstructive urology. RECENT FINDINGS: Even though many advocate the introduction of robot-assisted technique in reconstructive urology, relatively few studies have been published. Researchers do report shorter hospital stays and less blood loss than are reported for patients operated on with open reconstructive techniques and also report acceptable short-term outcomes. SUMMARY: The current literature shows that complex robot-assisted urological reconstructive surgical procedures may be used for both children and adults. With appropriate experience, this technique offers the expected advantages of decreased blood loss and transfusion rate, reduced analgesic requirements, and early hospital discharge in comparison with the open approach. However, robotic-assisted reconstructive urologic surgery needs to be evaluated in larger randomized studies with long-term follow-up. PMID- 21975507 TI - Congenital myasthenic syndrome with tubular aggregates caused by GFPT1 mutations. AB - Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous group of inherited disorders of the neuromuscular junction. A difficult to diagnose subgroup of CMS is characterised by proximal muscle weakness and fatigue while ocular and facial involvement is only minimal. DOK7 mutations have been identified as causing the disorder in about half of the cases. More recently, using classical positional cloning, we have identified mutations in a previously unrecognised CMS gene, GFPT1, in a series of DOK7 negative cases. However, detailed description of clinical features of GFPT1 patients has not been reported yet. Here we describe the clinical picture of 24 limb-girdle CMS (LG-CMS) patients and pathological findings of 18 of them, all carrying GFPT1 mutations. Additional patients with CMS, but without tubular aggregates, and patients with non-fatigable weakness with tubular aggregates were also screened. In most patients with GFPT1 mutations, onset of the disease occurs in the first decade of life with characteristic limb-girdle weakness and fatigue. A common feature was beneficial and sustained response to acetylcholinesterase inhibitor treatment. Most of the patients who had a muscle biopsy showed tubular aggregates in myofibers. Analysis of endplate morphology in one of the patients revealed unspecific abnormalities. Our study delineates the phenotype of CMS associated with GFPT1 mutations and expands the understanding of neuromuscular junction disorders. As tubular aggregates in context of a neuromuscular transmission defect appear to be highly indicative, we suggest calling this condition congenital myasthenic syndrome with tubular aggregates (CMS-TA). PMID- 21975510 TI - Current world literature. PMID- 21975512 TI - Epigenetic changes in B lymphocytes associated with house dust mite allergic asthma. AB - Although there is no doubt about the influence of the genetic background in the onset of the allergic diseases, Epigenome-Wide Association Studies are needed to elucidate the possible relationship between allergic diseases and epigenomic dysregulation. In this study we aimed to analyze the epigenetic patterns, in terms of DNA methylation, of three well-characterized populations of house dust mite allergic subjects, aspirin-intolerant asthmatics and controls. As a first, genome-wide phase, we used the HELP assay to study the methylation patterns in CD19 (+) B lymphocytes in these populations, and found that there are reproducible epigenetic differences at limited numbers of loci distinguishing the groups, corroborated by bisulphite MassArray in a second validation phase of an expanded 40 subject group. These validated epigenetic changes occur at loci characterized as important for the immune response. One such locus is a new candidate gene, CYP26A1, which shows differential methylation patterns and expression levels between groups. Our results suggest that epigenomic dysregulation may contribute to the susceptibility to allergic diseases, showing for the first time differences in DNA methylation between allergic and non allergic healthy subjects, both globally and at specific loci. These observations indicate that the epigenome may offer new pathophysiological insights and therapeutic targets in atopic diseases. PMID- 21975513 TI - Epigenetic regulation of gene expression in porcine epiblast, hypoblast, trophectoderm and epiblast-derived neural progenitor cells. AB - After fertilization, lineage specification is governed by a complicated molecular network in which permissiveness and repression of expression of pluripotency- and differentiation-associated genes are regulated by epigenetic modifications. DNA methylation operates as a very stable repressive mark in this process. In this study, we investigated the relationship between DNA methylation and expression of pluripotency-associated genes (OCT4, NANOG and SOX2), a trophectoderm (TE) specific gene (ELF5), and genes associated with neural differentiation (SOX2 and VIMENTIN) in porcine Day 10 (E10) epiblast, hypoblast, and TE as well as in epiblast-derived neural progenitor cells (NPCs). We found that OCT4, NANOG, and SOX2 were highly expressed in the epiblast and hypoblast, while VIMENTIN was only highly expressed in the epiblast. Moreover, low expression of OCT4, NANOG, SOX2 and VIMENTIN was noted in the TE. Most CpG sites of OCT4, NANOG, SOX2 and VIMENTIN displayed low methylation levels in the epiblast and hypoblast and, strikingly, also in the TE. Hence, the expression patterns of these genes were not directly related to levels of DNA methylation in the TE in contrast to the situation in the mouse. In contrast, ELF5 was exclusively expressed in the TE and was correspondingly hypomethylated in this tissue. In NPCs, we observed down regulation of NANOG and OCT4 expression, which correlated with hypermethylation of their promoters, whereas VIMENTIN displayed up-regulation in accordance with hypomethylation of its promoter. In conclusion, DNA methylation is an inconsistently operating epigenetic mechanism in porcine E10 blastocysts, whereas in porcine epiblast-derived NPCs, expression of pluripotency-associated and differentiation genes appear to be regulated by this modification. PMID- 21975515 TI - Application of synchrotron FTIR microspectroscopy for determination of spatial distribution of methylene blue conjugated onto a SAM via"click" chemistry. AB - We report, for the first time, the application of synchrotron FTIR microspectroscopy to determine the spatial distribution of methylene blue conjugated onto a self-assembled monolayer surface via Sharpless "click" chemistry. PMID- 21975516 TI - Nitrergic nerves derived from the pterygopalatine ganglion innervate arteries irrigating the cerebrum but not the cerebellum and brain stem in monkeys. AB - The functional roles of the nitrergic nerves innervating the monkey cerebral artery were evaluated in a tension-response study examining isolated arteries in vitro and cerebral angiography in vivo. Nicotine produced relaxation of arteries by stimulation of nerve terminals innervating isolated monkey arteries irrigating the cerebrum, cerebellum and brain stem. Relaxation of arteries induced by nicotine was abolished by treatment with N(G)-nitro-L-arginine, a nitric oxide synthase inhibitor, and was restored by addition of L-arginine. Cerebral angiography showed that electrical stimulation of the unilateral greater petrosal nerve, which connects to the pterygopalatine ganglion via the parasympathetic ganglion synapse, produced vasodilatation of the anterior, middle and posterior cerebral arteries in the stimulated side. However, stimulation failed to produce vasodilatation of the superior and anterior-inferior cerebellar arteries and the basilar artery in anesthetized monkeys. Therefore, nitrergic nerves derived from the pterygopalatine ganglion appear to regulate cerebral vasomotor function. In contrast, circulation in the cerebellum and brain stem might be regulated by nitrergic nerves originating not from the pterygopalatine ganglion, but rather from an unknown ganglion (or ganglia). PMID- 21975514 TI - Thermophilic proteins: insight and perspective from in silico experiments. AB - Proteins from thermophilic and hyperthermophilic organisms are stable and function at high temperatures (50-100 degrees C). The importance of understanding the microscopic mechanisms underlying this thermal resistance is twofold: it is key for acquiring general clues on how proteins maintain their fold stable and for targeting those medical and industrial applications that aim at designing enzymes that can work under harsh conditions. In this tutorial review we first provide the general background of protein thermostability by specifically focusing on the structural and thermodynamic peculiarities; next, we discuss how computational studies based on Molecular Dynamics simulations can broaden and refine our knowledge on such special class of proteins. PMID- 21975517 TI - Detection of Single Quantum Dots in Model Systems with Sheet Illumination Microscopy. AB - Single molecule detection and tracking provides at times the only possible method to observe the interactions of low numbers of biomolecules, inlcuding DNA, receptors and signal mediating proteins in living systems. However, most existing imaging methods do not enable both high sensitivity and non-invasive imaging of large specimens. In this study we report a new setup for selective plane illumination microscopy (SPIM), which enables fast imaging and single molecule tracking with the resolution of confocal microscopy and the optical penetration beyond 300 MUm. We detect and report our instrumental figures of merit, control values of fluorescence properties of single nano crystals in comparison to both standard widefield configurations, and also values of nanocrystals in multicellular "fruiting bodies" of Dictyostelium, an excellent control as a model developmental system. In the Dictyostelium , we also report some of our first tracking of single nanocrystals with SPIM. The new SPIM setup represents a new technique, which enables fast single molecule imaging and tracking in living systems. PMID- 21975519 TI - Printing of sub-20 nm wide graphene ribbon arrays using nanoimprinted graphite stamps and electrostatic force assisted bonding. AB - Nano-graphene ribbons are promising in many electronic applications, as their bandgaps can be opened by reducing the widths, e.g. below 20 nm. However, a high throughput method to pattern large-area nano-graphene features is still not available. Here we report a fabrication method of sub-20 nm ribbons on graphite stamps by nanoimprint lithography and a transfer-printing of the graphene ribbons to a Si wafer using electrostatic force assisted bonding. These methods provide a path for fast and high-throughput nano-graphene device production. PMID- 21975520 TI - Effects of vertebroplasty for delayed-onset paraplegia caused by vertebral pseudarthrosis. AB - BACKGROUND: The effectiveness of percutaneous vertebroplasty for osteoporotic vertebral pseudarthrosis with delayed-onset paraplegia has not been reported. We performed vertebroplasty for such patients and tried to investigate the effectiveness of this surgery. METHODS: We studied 11 patients (2001-2007) treated with percutaneous vertebroplasty for osteoporotic vertebral pseudarthrosis with delayed-onset paraplegia. The mean age of the patients was 71.9 +/- 5.2 years and the affected vertebrae were located in the thoracolumbar junction. The mean period between the onset of motor weakness and the day of the surgery was 9.5 +/- 5.7 weeks. Vertebroplasty was performed by filling the intravertebral cleft with polymethylmethacrylate. The clinical course was estimated using the Denis pain scale, the Eastern Cooperative Oncology Group performance status scale and the modified Medical Research Council grade before the surgery, 0, 1, 3, 6 months and 1 year following the surgery, and at the latest follow-up visit. The instability angle and local kyphotic angle were evaluated with X-rays. RESULTS: Significant improvements were observed in the pain scale in all patients, as they did not experience severe pain, and the performance status following the surgery. These conditions continued until the final clinical examination. Most patients had motor weakness, with a preoperative manual motor test score of 0-3, which gradually improved to 4-5 over the examination period. The stabilities of the affected vertebrae were confirmed on imaging at the final examination. Kyphotic changes were initially realigned, but a correction loss occurred in 7 of the 11 patients as a result of adjacent vertebral fractures. Increase in kyphosis following the surgery did not affect the muscle strength recovery. Bridging callus formations were observed around the affected vertebrae within 6 months in all cases. CONCLUSION: Percutaneous vertebroplasty for vertebral pseudarthrosis with delayed-onset paraplegia is effective for recovering muscle strength, improving performance status and relief from pain, despite local kyphosis. PMID- 21975521 TI - Reference values for hand grip strength, muscle mass, walking time, and one-leg standing time as indices for locomotive syndrome and associated disability: the second survey of the ROAD study. AB - BACKGROUND: We established reference values for hand grip strength, muscle mass, walking time, and one-leg standing time as indices reflecting components of locomotive syndrome and associated disability using a large-scale population based sample from the second survey of the Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) cohort. METHODS: We measured the above-mentioned indices in 2,468 individuals >= 40 years old (826 men, 1,642 women; mean age 71.8 years) during the second visit of the ROAD study. Disability was defined as certified disability according to the long-term care insurance system through public health centres of each municipality. RESULTS: Mean values for hand grip strength (weaker side), muscle mass of the thighs, walking time for 6 m at the usual pace, and the fastest pace for men were 32.7 kg, 7.0 kg, 5.6 s, and 3.7 s, respectively, and those for women were 20.8 kg, 5.2 kg, 5.9 s, and 4.1 s, respectively. The median values for one-leg standing time (weaker side) were 14 s for men and 12 s for women. The prevalence of disability in men aged 65-69, 70-74, 75-79, and >= 80 was 0.0, 1.0, 6.3, and 8.8%, respectively, and in women was 3.4, 3.5, 9.2, and 14.7%, respectively. There were significant associations between the presence of disability and walking time for 6 m at the usual pace and at the fastest pace, and between the presence of disability and walking speed. CONCLUSIONS: We established reference values for indices reflecting components of locomotive syndrome, and identified significant associations between walking ability and disability. PMID- 21975522 TI - Cervical intramedullary ependymoma masquerading as cervical spondylotic myelopathy on MRI analysis. PMID- 21975523 TI - A regulator's view of comparative effectiveness research. AB - BACKGROUND: 'Comparative effectiveness' is the current enthusiasm, and for good reason. After knowing a treatment works, the most critical question is how it compares with alternatives. Comparative studies are not commonly conducted by drug companies and they represent a significant methodological challenge. Comparative data could include evidence of overall superiority to an alternative or advantages in identifiable subsets, for example, people who do not respond to or tolerate alternatives, or members of a genetic subset and could also include convincing evidence that there is little difference between two treatments. PURPOSE: To describe regulations, guidance, and Food and Drug Administration experience related to studies of comparative effectiveness, including approaches to showing superiority and problems encountered in showing similarity. METHODS: Review of Food and Drug Administration regulations and guidance and experience with showing superiority and similarity, particularly related to randomized trials and epidemiologic studies. RESULTS: Methods exist, and they have been successful for showing overall superiority of one drug over another, advantages in specific population subsets. Efforts to show true equivalence face problems of definition and very large sample sizes needed to rule out small differences. LIMITATIONS: There is need for further discussion of what is meant by similarity or equivalence of two treatments. CONCLUSION: Comparative studies are challenging because differences between effective therapies are likely to be small and can be detected reliably only in randomized trials, often large ones. Despite the difficulties, comparative trials have been successful and we clearly would like to see more of them. PMID- 21975524 TI - Minimally invasive repair of central tarsal bone luxation in a dog. AB - OBJECTIVES: To describe the use of closed reduction and minimally invasive fixation for treatment of a central tarsal bone luxation in a six-year-old spayed female, mixed breed dog with acute onset non-weight bearing right hindlimb lameness. METHODS: Physical examination and tarsal radiographs resulted in a diagnosis of central tarsal bone luxation. Closed reduction and minimally invasive screw stabilization were performed with fluoroscopic guidance. External coaptation for six weeks was followed by a gradual return to full function. RESULTS: Follow-up examination at 34 months post-surgery revealed the patient to be fully functional on the surgically repaired limb. Radiographs revealed ankylosis of the intertarsal joints. CLINICAL SIGNIFICANCE: Minimally invasive ankle surgery is commonly performed in humans but is uncommon in dogs. Based on the results of this single case, minimally invasive reduction and stabilization of central tarsal bone luxation is feasible. PMID- 21975525 TI - An International Survey-based Algorithm for the Pharmacologic Treatment of Irritability in Huntington's Disease. AB - It is generally believed that treatments are available to manage irritability in Huntington's disease (HD). However, lack of an evidence base prevents the establishment of treatment guidelines for this symptom. The research literature fails to address behavioral intervention strategies, drug selection, drug dosing, management of inadequate response to a single drug, or preferred drugs when additional behavioral symptoms comorbid to irritability are present. In an effort to inform clinical decision-making we surveyed an international group of experts to address these points. The experts consistently endorsed an antipsychotic drug (APD) as first choice for treatment of urgent and aggressive irritability behaviors. However, there was variation in practice patterns for treating less severe symptoms. Serotonin reuptake inhibitors (SSRIs) were first choice drug treatments by most respondents across all geographic regions. However, APDs were also endorsed as first choice for mild or moderate irritability, more frequently in Europe than in North America and Australia. Antiepileptic mood stabilizers (AEDs) were used by fewer respondents as first choice drug. Perceived efficacy for control of mild or moderate irritability was judged somewhat higher for APDs than SSRIs or AEDs. Benzodiazepines were not used as monotherapy, but frequently as an adjunctive drug in the setting of comorbid anxiety. Though many cited lack of experience with mirtazapine, others familiar with its use in HD chose it as an alternative monotherapy, or as adjunctive therapy if insomnia was a comorbid factor. This report presents survey results, reviews available irritability studies, and lastly proposes an algorithm for the treatment of irritability in HD derived from expert preferences obtained through this survey. PMID- 21975526 TI - Immunology and Cell Biology Publication of the Year Awards 2010. PMID- 21975529 TI - Knee kinematic coupling in males and females: open and closed-chain tasks. AB - The purpose of this study was to compare the magnitude of knee kinematic coupling between genders and among open- and closed-chain tasks. A secondary purpose was to compare the consistency of knee kinematic coupling between genders and among open- and closed-chain tasks. Vector-coding methods were used to quantify coupling in the sagittal and transverse planes of the knee between full extension and 20 degrees of flexion as 10 males and 10 females walked, ascended and descended stairs, and performed a passive pendulum leg drop. An ANOVA showed no main effect of gender. There was a main effect of task, where coupling during the stance phase of walking was significantly greater than each of the other tasks. Intraclass correlation values suggested that males were slightly more consistent than females. A general lack of divergence between genders may be related to the tasks analyzed in this study. It is possible that more strenuous tasks may elicit larger differences. PMID- 21975530 TI - Longitudinal relationship between retinal nerve fiber layer thickness parameters assessed by scanning laser polarimetry (GDxVCC) and visual field in glaucoma. AB - PURPOSE: To investigate the longitudinal relationship between retinal nerve fiber layer (RNFL) thickness parameters assessed by scanning laser polarimetry with variable corneal compensation (GDxVCC) and visual field parameters obtained with the Humphrey field analyzer (HFA) in patients with glaucoma, and to assess the usefulness of GDxVCC in longitudinal follow-up. METHODS: A total of 242 eyes in 122 patients with glaucoma were periodically assessed using GDxVCC and HFA program SITA fast 30-2 for 3-5 years. Eyes with more than four times of reliable HFA and GDxVCC data were obtained from during the follow-up periods were included in the analysis. Changes in HFA parameters (mean deviation [MD], pattern standard deviation [PSD]) and those in GDxVCC parameters (superior average, inferior average, temporal-superior-nasal-inferior-temporal [TSNIT] average, TSNIT standard deviation [SD], nerve fiber indicator [NFI]) were determined by regression analysis. The relationship between HFA and GDxVCC parameters at the initial point and their annual changes were analyzed with canonical correlation analysis and Pearson's correlation coefficients. RESULTS: Twenty-four eyes (9.9%) of 19 patients that met inclusion criteria were statistically analyzed. Longitudinal progression was 0.039 +/- 0.971 dB/year in MD, 0.156 +/- 0.644 dB/year in PSD, -0.197 +/- 0.970 MUm/year in TSNIT average, -0.503 +/- 1.341 MUm/year in superior average, -0.282 +/- 0.974 MUm/year in inferior average, 0.284 +/- 1.013/year in TSNIT SD and 1.269 +/- 2.560/year in NFI. In canonical correlation analysis at the initial point, first canonical variates were not statistically significant between HFA and GDxVCC parameters. First canonical variates of annual changes significantly correlated between HFA and GDxVCC parameters (p < 0.01), with correlation coefficient of 0.85. In Pearson's correlation analysis of each parameter, there was a significant relationship between MD and NFI at the initial point (r = -0.46, p < 0.05). There was a statistically significant relationship between progressions in MD and NFI (r = 0.54, p < 0.01) and in PSD and NFI (r = 0.53, p < 0.01). CONCLUSIONS: Longitudinal progression in NFI obtained with GDxVCC was significantly correlated with that in HFA parameters, such as MD and PSD. GDxVCC is a useful tool for longitudinal follow-up assessment of glaucoma. PMID- 21975531 TI - Ciliary body cysts in neurofibromatosis: a new coexistence? AB - PURPOSE: Neurofibromatosis 1 (NF1) is an autosomal dominant, multisystem disorder that also effects the eye. Herein, we aimed to investigate the posterior iris surface and ciliary body morphology of NF1 patients by ultrasonic biomicroscopy (UB). MATERIALS & METHODS: Nine consecutive unrelated subjects with NF1, and as a control group 25 healthy subjects, were included in the study. All patients underwent ophthalmic examination including visual acuity testing, slit-lamp biomicroscopy, tonometry, gonioscopy (Schaffer classification), and dilated ophthalmoscopy, UB. RESULTS: Mean age was 35.1 +/- 16.2 (range, 11-57) and 34.5 +/- 15.6 (range, 9-60) for NF1 and control groups respectively (p>0.05). Lisch nodules were present in 16 of 18 eyes (88.8%) in NF1 group. Fundoscopic examination of the control group and 15 eyes of NF1 (83.3%) patients was normal, whereas hypoplastic and tilted optic nerve were present in three eyes, and temporally-located bone-spicule-like lesions was present in one eye of the NF1 group. UB revealed ciliary body cyst in 77.7% (14/18) of the eyes among NF1 group, and 8% (4/50) among control group (p<0.05). The mean size of the cysts were 520 +/- 191 MU (range, 220-860 MU) and 495 +/- 231 MU (range, 300-830 MU) at NF1 and control groups, respectively. Gonioscopic evaluation revealed that 55% of the NF1 patients have an unoccludable anterior chamber angle (Grade 3 or 4), 45% occludable angle (Grade 1 or 2), and 78% irregular pigment patches. However, occludable angle rate was just 4% in the control group, and none of the patients had irregular pigment patches. CONCLUSION: The coexistence of ciliary body cysts and NF1, and the effect of these cysts in the eye should be enlightened with further studies. PMID- 21975532 TI - Photosensitized electron transfer processes of nanocarbons applicable to solar cells. AB - Photosensitized electron-transfer processes of nanocarbon materials hybridized with electron donating or electron accepting molecules have been surveyed in this tutorial review on the basis of the recent results reported mainly from our laboratories. As nano-carbon materials, fullerenes and single wall carbon nanotubes (SWCNTs) have been employed. Fullerenes act as photo-sensitizing electron acceptors with respect to a wide variety of electron donors; in addition, the fullerenes act as good ground state electron acceptors in the presence of light-absorbing electron donors such as porphyrins and phthalocyanines. In the case of SWCNTs, their ground states act as electron acceptor and electron donors, depending on the photosensitizers. For example, with respect to the photoexcited porphyrins and phthalocyanines, SWCNTs usually act as electron acceptors, whereas for the photoexcited fullerenes, SWCNTs act as electron donors. The diameter sorted semi-conductive SWCNTs have been used to verify the size-dependent electron transfer rates. For the confirmation of the electron transfer processes, the transient absorption methods have been widely used, in addition to the time-resolved fluorescence spectral measurements. The kinetic data thus obtained in solution are found to be quite useful to predict the efficiencies of photovoltaic cells constructed on semiconductor nanoparticle modified electrodes and their photocatalytic processes. PMID- 21975533 TI - Trends in inpatient urinary incontinence surgery in the USA, 1998-2007. AB - INTRODUCTION AND HYPOTHESIS: This study was conducted to assess national rates in stress urinary incontinence (SUI) surgery in the USA from 1998 to 2007. METHODS: We utilized the 1998-2007 Nationwide Inpatient Sample and assessed women aged 20 years and older who underwent SUI surgery based on the International Classification of Diseases, 9th Revision (ICD-9) procedure and diagnosis codes. RESULTS: The total number of SUI surgeries performed during this 10-year period was 759,821. The annual number of procedures increased from 37,953 in 1998 to 94,910 in 2007. The type of SUI surgery performed also changed (p < 0.001). In 1998, retropubic suspensions represented 52.3%, decreasing to 13.8% in 2007. "Other repair of SUI" (ICD-9 59.79) comprised 22.4% in 1998, increasing to 75.2% in 2007, likely representing midurethral slings. CONCLUSIONS: The total number and incidence rates of SUI surgeries have increased from 1998 to 2007. The type of SUI surgery performed has also changed significantly, likely secondary to adoption of midurethral slings. PMID- 21975534 TI - Cobalt-doped cadmium selenide colloidal nanowires. AB - Co(2+)-doped CdSe colloidal nanowires with tunable size and dopant concentration have been prepared by a solution-liquid-solid (SLS) approach for the first time. These doped nanowires exhibit anomalous photoluminescence temperature dependence in comparison with undoped nanowires. PMID- 21975536 TI - [Tunneled hemodialysis catheters complications: a retrospective and monocentric comparative study of two devices]. AB - PURPOSE: In a monocentric retrospective study, two tunneled hemodialysis catheters have been compared: a twin cylinder catheter (Dualcath) and a split tip catheter (Hemosplit). PATIENTS AND METHODS: Patients who got catheters from January 1st 2007 to December 31st 2008 have been selected. Thrombotic events, as well as infectious events, were recorded in their dialysis file during this period of time. MAIN RESULTS: The study was carried out on 50 patients. Thirty of them were given Dualcath, 23 were given Hemosplit, and three both of them. A Kaplan-Meier analysis has enabled to draw up the catheter survival curves, and the log-rank test enables to establish a survival of 93.1% at 20 months for Dualcath while 42.2% for Hemosplit. As far as the thrombotic complications with catheter incident are concerned, their incidence is 25.5 and 46.4 out of 1000 catheter-days (P<0,0001). The ones with catheter manipulation have incidences of 6.78 and 9.33 out of 1000 catheter-days, respectively for Dualcath and Hemosplit (NS). Dualcath presents catheter-related infections with a rate of 4.38 out of 1000-catheter days while 5.07 for Hemosplit (NS). CONCLUSION: The Dualcath catheter presents a better survival than the Hemosplit catheter as well as weaker incident type thrombotic complications. PMID- 21975535 TI - Immune cell-mediated neuroprotection is independent of estrogen action through estrogen receptor-alpha. AB - It has been well documented that both estrogen and immune cells (CD4+ T cells) mediate neuroprotection in the mouse facial nerve axotomy model. Estrogen has been shown to play an important role in regulating the immune response. However, it is unclear whether immune cell-mediated neuroprotection is dependent on estrogen signaling. In this study, using FACS staining, we confirmed that the majority of CD4+ T cells express high levels of estrogen receptor-alpha (ERalpha), suggesting that CD4+ T cell-mediated neuroprotection may be modulated by estrogen signaling. We previously found that immunodeficient Rag-2KO mice showed a significant increase in axotomy-induced facial motoneuron death compared to immunocompetent wild-type mice. Therefore, we investigated axotomy-induced facial motoneuron loss in immunodeficient Rag-2KO mice that received 17beta estradiol treatment or adoptive transfer of immune cells from mice lacking functional ERalpha. Our results indicate that while estradiol treatment failed to rescue facial motoneurons from axotomy-induced cell death in Rag-2KO mice, immune cells lacking ERalpha successfully restored facial motoneuron survival in Rag-2 KO mice to a wild-type level. Collectively, we concluded that CD4+ T cell mediated neuroprotection is independent of estrogen action through ERalpha. PMID- 21975537 TI - [Genetic polymorphisms: how to interpret studies?]. AB - During the last years, publications upon potential association between genetic polymorphisms and clinical outcomes have exponentially increased. Conflicting results between similar studies have contributed to seriously distrust the validity of this approach. This review emphasizes on intrinsic properties of SNP and methodological prerequisites for such studies. PMID- 21975539 TI - Combined DFT and BS study on the exchange coupling of dinuclear sandwich-type POM: comparison of different functionals and reliability of structure modeling. AB - The exchange coupling of a group of three dinuclear sandwich-type polyoxomolybdates [MM'(AsMo7O27)2](12-) with MM' = CrCr, FeFe, FeCr are theoretically predicted from combined DFT and broken-symmetry (BS) approach. Eight different XC functionals are utilized to calculate the exchange-coupling constant J from both the full crystalline structures and model structures of smaller size. The comparison between theoretical values and accurate experimental results supports the applicability of DFT-BS method in this new type of sandwich type dinuclear polyoxomolybdates. However, a careful choice of functionals is necessary to achieve the desired accuracy. The encouraging results obtained from calculations on model structures highlight the great potential of application of structure modeling in theoretical study of POM. Structural modeling may not only reduce the computational cost of large POM species but also be able to take into account the external field effect arising from solvent molecules in solution or counterions in crystal. PMID- 21975540 TI - Molecular modeling of temperature dependence of solubility parameters for amorphous polymers. AB - A molecular modeling strategy is proposed to describe the temperature (T) dependence of solubility parameter (delta) for the amorphous polymers which exhibit glass-rubber transition behavior. The commercial forcefield "COMPASS" is used to support the atomistic simulations of the polymer. The temperature dependence behavior of delta for the polymer is modeled by running molecular dynamics (MD) simulation at temperatures ranging from 250 up to 650 K. Comparing the MD predicted delta value at 298 K and the glass transition temperature (T(g)) of the polymer determined from delta-T curve with the experimental value confirm the accuracy of our method. The MD modeled relationship between delta and T agrees well with the previous theoretical works. We also observe the specific volume (v), cohesive energy (U(coh)), cohesive energy density (E(CED)) and delta shows a similar temperature dependence characteristics and a drastic change around the T(g). Meanwhile, the applications of delta and its temperature dependence property are addressed and discussed. PMID- 21975541 TI - Size and chain length effects on structural behaviors of biphenylcyclohexane based liquid crystal nanoclusters by a coarse-grained model. AB - Size and chain length effects on structural behaviors of liquid crystal nanoclusters were examined by a coarse-grained model and the configurational-bias Monte Carlo (CBMC) simulation. The nanoclusters investigated in this study are composed of the biphenylcyclohexane-based BCH5H liquid crystal molecule and its derivatives. Results of the study show that the average energy decreases (i.e., more negative) as the cluster size (i.e., the number of molecules) increases. With the increasing cluster size, the equilibrium conformation of the nanocluster changes gradually from a pipe-like structure (for the smaller systems) to a ball like cluster (for the larger systems). The order parameter of the system reduces with the transition of the equilibrium conformation. Regarding the chain length effect, the pipe-like equilibrium conformation (for the smaller systems) was observed more close to a pipe as the length of the tail alkyl chain of the derivatives extended. However, due to the flexibility of the tail alkyl chain, the pipe conformation of the system deflects slightly about its cyclohexyl group as the tail extends further. PMID- 21975542 TI - Improvement of oxygen reduction reaction and methanol tolerance characteristics for PdCo electrocatalysts by Au alloying and CO treatment. AB - The mass ORR activity of CO heat-treated PdCoAu/C catalysts, compared to Pd/C, is enhanced approximately 6-fold, and even 25-fold in a methanol containing environment due to the formation of delicate PdCo and PdAu alloys enriched in the core and PdAu alloy species enriched on the shell structure. PMID- 21975543 TI - Supercurrent through InAs nanowires with highly transparent superconducting contacts. AB - One-dimensional superconducting transistors have been fabricated with individual InAs nanowires (NWs) using radio-frequency sputter cleaning followed by in situ metal deposition. Because of the highly transparent contacts formed in between the InAs NWs and the metals, supercurrent, multiple Andreev reflections and Shapiro steps under microwave radiation have been observed. Near pinch-off gate regions, Fabry-Perot interference and a normal conductance quantization with resonant features have been observed, which were found to be correlated with a supercurrent flow. PMID- 21975544 TI - Practical guide to choosing an appropriate data display. AB - The primary objective of graphing research data is to communicate key information visually in a rapid, accurate, and concise way. Graphs might be considered visual take-home lessons of the major point(s) of the manuscript. In choosing a graph, it is tempting to concentrate only on ways of illustrating summary statements characterizing the group(s). However, individual patients are unique, and their characteristics or outcomes may not be predicted by a group summary. Consequently, if possible, graphs should demonstrate individual responses as well as group summaries. "Graphical literacy," "graphical excellence," and "graphical acumen" are achievable with work and collaboration. To produce a well-designed graph, a combination of by-subject detail and overall results should be the goal within the same illustration. The practice gap addressed in this article is that little attention from authors, reviewers, editors, and publishers seems to be paid to graphical literacy. The purpose of this article is to present some practical guidelines for choosing or evaluating more appropriate data displays. PMID- 21975545 TI - Quantitative and phenotypic analysis of bone marrow-derived cells in the intact and inflamed central nervous system. AB - Bone marrow has been proposed as a possible source of cells capable of replacing injured neural cells in diseases such as Multiple Sclerosis (MS). Previous studies have reported conflicting results regarding the transformation of bone marrow cells into neural cells in vivo. This study is a detailed analysis of the fate of bone marrow derived cells (BMDC) in the CNS of C57Bl/6 mice with and without experimental autoimmune encephalomyelitis using flow cytometry to identify GFP-labeled BMDC that lacked the pan-hematopoietic marker, CD45 and co expressed neural markers polysialic acid-neural cell adhesion molecule or A2B5. A small number of BMDC displaying neural markers and lacking CD45 expression was identified within both the non-inflamed and inflamed CNS. However, the majority of BMDC exhibited a hematopoietic phenotype. PMID- 21975546 TI - Phenylboronic acid is a more potent inhibitor than boric acid of key signaling networks involved in cancer cell migration. AB - Previous studies from our lab have shown that both boric (BA) and phenylboronic- acid (PBA) inhibit the migration of prostate cancer cell lines, as well as non tumorigenic prostate cells. Our results indicate that PBA is more potent than BA in targeting metastatic and proliferative properties of cancer cells. Here we focus on the impact of BA and PBA on Rho family of GTP-binding proteins and their downstream targets. Treatment with 1mM PBA and BA decreases activities of RhoA, Rac1, and Cdc42 in DU-145 metastatic prostate cancer cells, but not in normal RWPE-1 prostate cells. Furthermore, ROCKII activity and phosphorylation of myosin light chain kinase decrease as a result of either PBA or BA treatment in DU-145 cells, suggesting these compounds target actomyosin-based contractility. PMID- 21975547 TI - C. elegans as a genetic model to identify novel cellular and molecular mechanisms underlying nervous system regeneration. AB - Research into conditions that improve axon regeneration has the potential to open a new door for treatment of brain injury caused by stroke and neurodegenerative diseases of aging, such as Alzheimer, by harnessing intrinsic neuronal ability to reorganize itself. Elucidating the molecular mechanisms of axon regeneration should shed light on how this process becomes restricted in the postnatal stage and in CNS and therefore could provide therapeutic targets for developing strategy to improve axon regeneration in adult CNS. In this review, we first discuss the general view about nerve regeneration and the advantages of using C. elegans as a model system to study axon regeneration. We then compare the conserved regeneration patterns and molecular mechanisms between C. elegans and vertebrates. Lastly, we discuss the power of femtosecond laser technology and its application in axon regeneration research. PMID- 21975548 TI - Integrin alpha9 (ITGA9) expression and epigenetic silencing in human breast tumors. AB - Integrin alpha9 (ITGA9) is one of the less studied integrin subunits that facilitates accelerated cell migration and regulates diverse biological functions such as angiogenesis, lymphangiogenesis, cancer cell proliferation and migration. In this work, integrin alpha9 expression and its epigenetic regulation in normal human breast tissue, primary breast tumors and breast cancer cell line MCF7 were studied. It was shown that integrin alpha9 is expressed in normal human breast tissue. In breast cancer, ITGA9 expression was downregulated or lost in 44% of tumors while another 45% of tumors showed normal or increased ITGA9 expression level (possible aberrations in the ITGA9 mRNA structure were supposed in 11% of tumors). Methylation of ITGA9 CpG-island located in the first intron of the gene was shown in 90% of the breast tumors with the decreased ITGA9 expression while no methylation at 5'-untranslated region of ITGA9 was observed. 5-aza-dC treatment restored integrin alpha9 expression in ITGA9-negative MCF7 breast carcinoma cells, Trichostatin A treatment did not influenced it but a combined treatment of the cells with 5-aza-dC/Trichostatin A doubled the ITGA9 activation. The obtained results suggest CpG methylation as a major mechanism of integrin alpha9 inactivation in breast cancer with a possible involvement of other yet unidentified molecular pathways. PMID- 21975549 TI - Filopodia initiation: focus on the Arp2/3 complex and formins. AB - Filopodia are long, slender, actin-rich cellular protrusions, which recently have become a focus of cell biology research because of their proposed roles as sensory and exploratory organelles that allow for "intelligent" cell behavior. Actin nucleation, elongation and bundling are believed to be essential for filopodia formation and functions. However, the identity of actin filament nucleators responsible for the initiation of filopodia remains controversial. Two alternative models, the convergent elongation and tip nucleation, emphasize two different actin filament nucleators, the Arp2/3 complex or formins, respectively, as key players during filopodia initiation. Although these two models in principle are not mutually exclusive, it is important to understand which of them is actually employed by cells. In this review, we discuss the existing evidence regarding the relative roles of the Arp2/3 complex and formins in filopodia initiation. PMID- 21975551 TI - Filopodia and adhesion in cancer cell motility. AB - Slender bundled actin containing plasma membrane protrusions, called filopodia, are important for many essential cellular processes like cell adhesion, migration, angiogenesis and the formation of cell-cell contacts. In migrating cells, filopodia are the pioneers at the leading edge which probe the environment for cues. Integrins are cell surface adhesion receptors critically implicated in cell migration and they are transported actively to filopodia tips by an unconventional myosin, myosin-X. Integrin mediated adhesion stabilizes filopodia and promotes cell migration even though integrins are not essential for filopodia initiation. Myosin-X binds also PIP3 and this regulates its activation and localization to filopodia. Filopodia stimulate cell migration in many cell types and increased filopodia density has been described in cancer. Furthermore, several proteins implicated in filopodia formation, like fascin, are also relevant for cancer progression. To investigate this further, we performed a meta analysis of the expression profiles of 10 filopodia-linked genes in human breast cancer. These data implicated that several different filopodia inducing genes may contribute in a collective manner to cancer progression and the high metastasis rates associated with basal-type breast carcinomas. PMID- 21975552 TI - The filopodium: a stable structure with highly regulated repetitive cycles of elongation and persistence depending on the actin cross-linker fascin. AB - The ability of mammalian cells to adhere and to migrate is an essential prerequisite to form higher organisms. Early migratory events include substrate sensing, adhesion formation, actin bundle assembly and force generation. Latest research revealed that filopodia are important not only for sensing the substrate but for all of the aforementioned highly regulated processes. However, the exact regulatory mechanisms are still barely understood. Here, we demonstrate that filopodia of human keratinocytes exhibit distinct cycles of repetitive elongation and persistence. A single filopodium thereby is able to initiate the formation of several stable adhesions. Every single filopodial cycle is characterized by an elongation phase, followed by a stabilization time and in many cases a persistence phase. The whole process is strongly connected to the velocity of the lamellipodial leading edge, characterized by a similar phase behavior with a slight time shift compared to filopodia and a different velocity. Most importantly, re-growth of existing filopodia is induced at a sharply defined distance between the filopodial tip and the lamellipodial leading edge. On the molecular level this re-growth is preceded by a strong filopodial reduction of the actin bundling protein fascin. This reduction is achieved by a switch to actin polymerization without fascin incorporation at the filopodial tip and therefore subsequent out-transport of the cross-linker by actin retrograde flow. PMID- 21975550 TI - The role of actin bundling proteins in the assembly of filopodia in epithelial cells. AB - The goal of this review is to highlight how emerging new models of filopodia assembly, which include tissue specific actin-bundling proteins, could provide more comprehensive representations of filopodia assembly that would describe more adequately and effectively the complexity and plasticity of epithelial cells. This review also describes how the true diversity of actin bundling proteins must be considered to predict the far-reaching significance and versatile functions of filopodia in epithelial cells. PMID- 21975553 TI - S100A4 downregulates filopodia formation through increased dynamic instability. AB - Cell migration requires the initial formation of cell protrusions, lamellipodia and/or filopodia, the attachment of the leading lamella to extracellular cues and the formation and efficient recycling of focal contacts at the leading edge. The small calcium binding EF-hand protein S100A4 has been shown to promote cell motility but the direct molecular mechanisms responsible remain to be elucidated. In this work, we provide new evidences indicating that elevated levels of S100A4 affect the stability of filopodia and prevent the maturation of focal complexes. Increasing the levels of S100A4 in a rat mammary benign tumor derived cell line results in acquired cellular migration on the wound healing scratch assay. At the cellular levels, we found that high levels of S100A4 induce the formation of many nascent filopodia, but that only a very small and limited number of those can stably adhere and mature, as opposed to control cells, which generate fewer protrusions but are able to maintain these into more mature projections. This observation was paralleled by the fact that S100A4 overexpressing cells were unable to establish stable focal adhesions. Using different truncated forms of the S100A4 proteins that are unable to bind to myosin IIA, our data suggests that this newly identified functions of S100A4 is myosin-dependent, providing new understanding on the regulatory functions of S100A4 on cellular migration. PMID- 21975554 TI - Protein fluxes along the filopodium as a framework for understanding the growth retraction dynamics: the interplay between diffusion and active transport. AB - We present a picture of filopodial growth and retraction from physics perspective, where we emphasize the significance of the role played by protein fluxes due to spatially extended nature of the filopodium. We review a series of works, which used stochastic simulations and mean field analytical modeling to find the concentration profile of G-actin inside a filopodium, which, in turn, determines the stationary filopodial length. In addition to extensively reviewing the prior works, we also report some new results on the role of active transport in regulating the length of filopodia. We model a filopodium where delivery of actin monomers towards the tip can occur both through passive diffusion and active transport by myosin motors. We found that the concentration profile of G actin along the filopodium is rather non-trivial, containing a narrow minimum near the base followed by a broad maximum. For efficient enough actin transport, this non-monotonous shape is expected to occur under a broad set of conditions. We also raise the issue of slow approach to the stationary length and the possibility of multiple steady state solutions. PMID- 21975555 TI - The ICI classification for calcaneal injuries: a validation study. AB - INTRODUCTION: The integral classification of injuries (ICI), by Zwipp et al. has been developed as a classification system for injuries of the bones, joints, cartilage and ligaments of the foot. It follows the principles of the comprehensive classification of fractures by Muller et al. The ICI was developed for 'everyday use' and scientific purposes. Our aim was to perform a validation study for this classification system applied to the calcaneal injuries. METHODS: A panel of five experienced trauma and orthopaedic surgeons evaluated the ICI score in 20 calcaneal injuries. After 2 months, a second classification was performed in a different order. Inter- and intra-observer variability were evaluated by kappa statistics. RESULTS: Panel members were not able to evaluate capsule and ligamental injuries based on X-ray and computed tomography (CT) films. Two injuries were excluded for logistical reasons. The inter-observer agreement based on 18 injuries of bone and joints was slight; kappa 0.14 (90% confidence interval (CI): 0.05-0.22). The intra-observer agreement was fair; kappa 0.31 (90% CI: 0.22-0.41). Overall, the panel rated the system as very complicated and not practical. CONCLUSION: The ICI is a complicated classification system with slight to fair inter- and intra-observer variabilities. It might not be a practical classification system for calcaneal injuries in 'everyday use' or scientific purposes. PMID- 21975556 TI - Selective faecal diversion in open pelvic fractures: reassessment based on recent experience. PMID- 21975557 TI - Carboxyl and negative charge-functionalized superparamagnetic nanochains with amorphous carbon shell and magnetic core: synthesis and their application in removal of heavy metal ions. AB - This communication describes carboxyl-functionalized nanochains with amorphous carbon shell (18 nm) and magnetic core using ferrocene as a single reactant under the induction of an external magnetic field (0.40 T), which shows a superparamagnetic behavior and magnetization saturation of 38.6 emu g(-1). Because of mesoporous structure (3.8 nm) and surface negative charge (-35.18 mV), the nanochains can be used as adsorbent for removing the heavy metal ions (90%) from aqueous solution. PMID- 21975558 TI - Long-term administration of quarterly IV ibandronate is effective and well tolerated in postmenopausal osteoporosis: 5-year data from the DIVA study long term extension. AB - Long-term bone mineral density (BMD) gains, bone marker levels, and safety of 3 mg quarterly intravenous (IV) ibandronate were studied in this 3-year extension to the Dosing IntraVenous Administration (DIVA) trial. Quarterly IV ibandronate consistently increased lumbar spine bone mineral density measured with dual energy X-ray absorptiometry (DXA-BMD) over 5 years (8.1%) and was well tolerated in women with postmenopausal osteoporosis. INTRODUCTION: Treatment with IV ibandronate regimens, 2 mg bimonthly and 3 mg quarterly, has been studied for up to 5 years in a long-term extension (LTE) to the 2-year DIVA trial. METHODS: DIVA LTE is an open-label extension to a 2-year randomized, double-blind, double dummy, noninferiority, phase III study (DIVA core). DIVA LTE involved postmenopausal women who had completed 2 years of DIVA core, comparing daily oral and IV ibandronate (>=75% adherence with IV ibandronate in year 2 of DIVA). Patients previously treated with 2 mg bimonthly or 3 mg quarterly IV ibandronate continued on the same regimen; patients who had received 2.5 mg daily oral ibandronate and placebo IV in DIVA core were switched to IV ibandronate. RESULTS: Pooled analysis of 497 intent-to-treat (ITT) patients receiving IV ibandronate from DIVA core baseline showed consistent increases over 5 years in lumbar spine DXA-BMD (8.4% [95% confidence interval (CI) = 7.5, 9.3] with 2 mg bimonthly and 8.1% [95% CI = 7.2, 8.9] with 3 mg quarterly). Three-year data relative to DIVA LTE baseline in the full ITT population (756 patients randomized or reallocated from DIVA, including those previously on daily treatment) showed maintenance of DXA-BMD gains from DIVA core with further gains in lumbar spine DXA-BMD. These benefits are supported by sustained reductions in markers of bone metabolism. No tolerability concerns or new safety signals were observed. CONCLUSIONS: Treatment with IV ibandronate 2 mg bimonthly or 3 mg quarterly is effective and well tolerated for up to 5 years in women with postmenopausal osteoporosis. PMID- 21975559 TI - Post hoc analysis of a single IV infusion of zoledronic acid versus daily oral risedronate on lumbar spine bone mineral density in different subgroups with glucocorticoid-induced osteoporosis. AB - This study summarizes the treatment effect of zoledronic acid infusion on lumbar spine bone mineral density in different subgroups with glucocorticoid-induced osteoporosis. Zoledronic acid is significantly more effective than risedronate in increasing lumbar spine (LS) bone mineral density (BMD) in both prevention and treatment of glucocorticoid-induced osteoporosis. Introduction In patients on glucocorticoids, a single zoledronic acid infusion significantly increased BMD versus daily oral risedronate. We assessed treatment effect on LS BMD in different patient subgroups at month 12 that contributed to the risk of osteoporosis in addition to glucocorticoids. Methods Patients randomized to a single IV infusion of zoledronic acid 5 mg or risedronate (5 mg/day) and stratified based on glucocorticoids duration [treatment (>3 months) and prevention (<= 3 months) subpopulations]were subgrouped by age; gender; menopausal status in women; dose and duration of prednisone during the trial; and baseline serum 25-OH vitamin D, LS BMD T-score, creatinine clearance, and concomitant medication use. Results At month 12, zoledronic acid significantly increased LS BMD versus risedronate in patients <= 74 years (P<0.05) in the treatment and 65-74 years (P = 0.0008) in the prevention subpopulation. At month 12, zoledronic acid significantly increased LS BMD versus risedronate in both subpopulations irrespective of gender (all P<0.05), cumulative prednisone dose (all P<0.01), and postmenopausal status (all P<0.05). In premenopausal women, in both subpopulations, zoledronic acid significantly increased total hip BMD (all P<0.05) versus risedronate at month 12 but not LS BMD. Osteoporotic patients in the prevention (P=0.0189) and osteopenic patients in the treatment subpopulation (P=0.0305) showed significant LS BMD increases with zoledronic acid versus risedronate at month 12. Conclusions This post hoc analysis suggests that zoledronic acid is significantly more effective than risedronate in increasing LS BMD in prevention and treatment of glucocorticoid-induced osteoporosis across a wide range of patients. PMID- 21975560 TI - The importance of morphometric radiographic vertebral assessment for the detection of patients who need pharmacological treatment of osteoporosis among postmenopausal diabetic Korean women. AB - Many diabetic patients with vertebral fractures remain undiagnosed and untreated. We found that more than two-thirds of osteoporotic diabetic women could not be identified for pharmacological treatment according to the NOF guidelines if without radiographic vertebral assessment. This study shows the importance of radiographic vertebral assessment for identifying patients who need treatment for osteoporosis in diabetic women. INTRODUCTION: Diagnosis of vertebral fracture (VF) is important for identifying patients who need pharmacologic therapy for osteoporosis. However, many patients with vertebral fractures remain undiagnosed and untreated. This study evaluated the number of patients with VFs who would be unrecognized as candidates for osteoporosis treatments according to the National Osteoporosis Foundation (NOF) Clinician's Guidelines to the Treatment of Osteoporosis, among postmenopausal diabetic Korean women without spinal imaging. METHODS: A total of 873 postmenopausal diabetic women were enrolled. Lateral plain radiographs of the thoracolumbar spine and total hip BMD were obtained. The Fracture Risk Assessment Tool (FRAX(r)) probability was computed using the algorithm available online at http://www.shef.ac.uk/FRAX (South Korea version). The subjects with and without VFs were classified into candidates for osteoporosis treatment [Tx+by NOF] and not candidates for osteoporosis treatment [Tx-by NOF] according to the NOF pharmacologic treatment guidelines, regardless of the presence of VFs. RESULTS: Forty-six percent of postmenopausal diabetic womenhad morphometric VFs. Among the subjects with morphometric VFs, only 2% of the patients had previously diagnosed VFs by medical doctors. In addition, 73.6% of the patients with VFs were not included in the [Tx+by NOF] group, given the assumption of no radiographic diagnosis of VFs. CONCLUSIONS: With regard to increased risk of VFs in postmenopausal Korean women with type 2 diabetes mellitus, radiographic vertebral assessment would be useful for the clinical identification of osteoporosis and fractures. PMID- 21975563 TI - Fast and direct measurements of the electrical properties of graphene using micro four-point probes. AB - We present measurements of the electronic properties of graphene using a repositionable micro four-point probe system, which we show here to have unique advantages over measurements made on lithographically defined devices; namely speed, simplicity and lack of a need to pattern graphene. Measurements are performed in ambient, vacuum and controlled environmental conditions using an environmental scanning electron microscope (SEM). The results are comparable to previous results for microcleaved graphene on silicon dioxide (SiO(2)). We observe a pronounced hysteresis of the charge neutrality point, dependent on the sweep rate of the gate voltage; and environmental measurements provide insight into the sensor application prospects of graphene. The method offers a fast, local and non-destructive technique for electronic measurements on graphene, which can be positioned freely on a graphene flake. PMID- 21975561 TI - T-cadherin (Cdh13) in association with pancreatic beta-cell granules contributes to second phase insulin secretion. AB - Glucose homeostasis depends on adequate control of insulin secretion. We report the association of the cell-adhesion and adiponectin (APN)-binding glycoprotein T cadherin (Cdh13) with insulin granules in mouse and human beta-cells. Immunohistochemistry and electron microscopy of islets in situ and targeting of RFP-tagged T-cadherin to GFP-labeled insulin granules in isolated beta-cells demonstrate this unusual location. Analyses of T-cadherin-deficient (Tcad-KO) mice show normal islet architecture and insulin content. However, T-cadherin is required for sufficient insulin release in vitro and in vivo. Primary islets from Tcad-KO mice were defective in glucose-induced but not KCl-mediated insulin secretion. In vivo, second phase insulin release in T-cad-KO mice during a hyperglycemic clamp was impaired while acute first phase release was unaffected. Tcad-KO mice showed progressive glucose intolerance by 5 mo of age without concomitant changes in peripheral insulin sensitivity. Our analyses detected no association of APN with T-cadherin on beta-cell granules although colocalization was observed on the pancreatic vasculature. These data identify T-cadherin as a novel component of insulin granules and suggest that T-cadherin contributes to the regulation of insulin secretion independently of direct interactions with APN. PMID- 21975564 TI - Light-initiated hydroxylation of lauric acid using hybrid P450 BM3 enzymes. AB - We have developed hybrid P450 BM3 enzymes consisting of a Ru(II)-diimine photosensitizer covalently attached to non-native single cysteine residues of P450 BM3 heme domain mutants. These enzymes are capable, upon light activation, of selectively hydroxylating lauric acid with 40 times higher total turnover numbers compared to the peroxide shunt. PMID- 21975565 TI - Novel 1-indanone Thiosemicarbazone Antiviral Candidates: Aqueous Solubilization and Physical Stabilization by Means of Cyclodextrins. AB - PURPOSE: To investigate cyclodextrin-mediated solubilization and physical stabilization of novel 1-indanone thiosemicarbazone (TSC) candidate drugs that display extremely high self-aggregation and precipitation tendency in water. METHODS: TSC/CD complexes were produced by co-solvent method, and TSC/CD phase solubility diagrams were obtained by plotting TSC concentration as a function of increasing CD concentration. Size, size distribution, and zeta-potential of the different TSC/CD complexes and aggregates were fully characterized by dynamic light scattering. The morphology of the structures was visualized by atomic force microscopy. RESULTS: Results indicated the formation of Type A inclusion complexes; the solubility of different TSCs was enhanced up to 215 times. The study of physical stability revealed that, as opposed to free TSCs that self aggregate, crystallize, and precipitate in water very rapidly, complexed TSCs remain in solution for at least 1 week. On the other hand, a gradual size growth was observed. This phenomenon stemmed from the self-aggregation of the TSC/CD complex. CONCLUSIONS: 1-indanone TSC/CD inclusion complexes improved aqueous solubility and physical stability of these new drug candidates and constitute a promising technological approach towards evaluation of their activity against the viruses hepatitis B and C. PMID- 21975566 TI - The promise of inhibition of smooth muscle tone as a treatment for erectile dysfunction: where are we now? AB - Ten years ago, the inhibition of Rho kinase by intracavernosal injection of Y 27632 was found to induce an erectile response. This effect did not require activation of nitric oxide-mediated signaling, introducing a novel target pathway for the treatment of erectile dysfunction (ED), with potential added benefit in cases where nitric oxide bioavailability is attenuated (and thus phosphodiesterase type 5 (PDE5) inhibitors are less efficacious). Rho-kinase antagonists are currently being developed and tested for a wide range of potential uses. The inhibition of this calcium-sensitizing pathway results in blood vessel relaxation. It is also possible that blockade of additional smooth muscle contractile signaling mechanisms may have the same effect. In this review, we conducted an extensive search of pertinent literature using PUBMED. We have outlined the various pathways involved in the maintenance of penile smooth muscle tone and discussed the current potential benefit for the pharmacological inhibition of these targets for the treatment of ED. PMID- 21975568 TI - Effect of the length of the superficial plate on bending stiffness, bending strength and strain distribution in stacked 2.0-2.7 veterinary cuttable plate constructs. An in vitro study. AB - OBJECTIVES: Use of stacked veterinary cuttable plates (VCP) increases the construct stiffness, but it also increases the stress protection and concentrates the stress at the extremities of the implants. We hypothesized that by shortening the superficial plate, it would not reduce the stiffness of the construct, but that it would reduce the stress concentration at the plate ends. METHODS: A 3 mm fracture gap model was created with copolymer acetal rods, stacked 2.0-2.7 VCP and 2.7 screws. The constructs consisted of an 11-hole VCP bottom plate and a 5-, 7-, 9- or 11-hole VCP superficial plate. Five of each construct were randomly tested for failure in four-point bending and axial loading. Stiffness, load at yield, and area under the curve until contact (AUC) were measured. Strains were recorded during elastic deformation for each configuration. RESULTS: During both testing methods, stiffness, load at yield and AUC progressively decreased when decreasing the length of the superficial plate. No statistically significant differences were obtained for load at yield in four-point bending and AUC in axial loading. The strain within the implant over the gap increased as the length of the superficial plate decreased. CLINICAL SIGNIFICANCE: Shortening the superficial plate reduces the stiffness and strength of the construct, and decreases stress concentration at the implants ends. As the cross section of the implant covering the gap remained constant, friction between the plates may play a role in the mechanical properties of stacked VCP. PMID- 21975569 TI - Isomorphous tetrazolate MnII and CoII compounds built on Delta-chain showing different magnetic behaviors. AB - As a continuation of the study on using the tetrazolate ligands to construct coordination polymers, two isomorphous 3D coordination polymers built on Delta chain topological rod-shaped SBUs have been synthesized with formulae [M(2)(MU(3) OH)L(1)L(2)](n) (5-amino-1H-tetrazole (HL(1)), 2,3-pyrazinedicarboxylic acid (H(2)L(2)) and different 3d spin carriers (M = Mn(II), 1 and Co(II), 2)). The SBU consists of corner-sharing [M(3)(MU(3)-OH)] isosceles triangle motifs with mixed multiple (MU(4)-tetrazolyl, MU(3)-OH, syn-syn carboxylate) bridges. The SBUs were further linked by syn-anti carboxylates to form the sra net. Spin-competing was observed in the Mn(II) compound, whereas the Co(II) compound exhibits spin canting. PMID- 21975567 TI - Increased cavernosal relaxation by Phoneutria nigriventer toxin, PnTx2-6, via activation at NO/cGMP signaling. AB - Erectile dysfunction (ED) mechanisms in diabetic patients are multifactorial and often lead to resistance to current therapy. Animal toxins have been used as pharmacological tools to study penile erection. Human accidents involving the venom of Phoneutria nigriventer spider are characterized by priapism. We hypothesize that PnTx2-6 potentiates cavernosal relaxation in diabetic mice by increasing cyclic guanosine monophosphate (cGMP). This effect is neuronal nitric oxide synthase (nNOS) dependent. Cavernosal strips were contracted with phenylephrine (10(-5) M) and relaxed by electrical field stimulation (20 V, 1-32 Hz) in the presence or absence of PnTx2-6 (10(-8) M). Cavernosal strips from nNOS and endothelial nitric oxide synthase (eNOS)-knockout (KO) mice, besides nNOS inhibitor (10(-5) M), were used to evaluate the role of this enzyme in the potentiation effect evoked by PnTx2-6. Tissue cGMP levels were determined after stimulation with PnTx2-6 in presence or absence of N-nitro-L-arginine methyl ester (L-NAME) (10(-4) M) and omega-conotoxin GVIA (10(-6) M), an N-type calcium channel inhibitor. Results showed that PnTx2-6 enhanced cavernosal relaxation in diabetic mice (65%) and eNOS KO mice, but not in nNOS KO mice. The toxin effect in the cavernosal relaxation was abolished by nNOS inhibitor. cGMP levels are increased by PnTx2-6, however, L-NAME abolished this enhancement as well as omega conotoxin GVIA. We conclude that PnTx2-6 facilitates penile relaxation in diabetic mice through a mechanism dependent on nNOS, probably via increasing nitric oxide/cGMP production. PMID- 21975573 TI - Functionalization of DNA nanostructures with proteins. AB - Proteins possess intrinsic functionalities, which have been optimized in billions of years of natural evolution. The conjugation of proteins with artificial nucleic acids allows one to further functionalize proteins with a synthetically accessible, physicochemically robust tag, which is addressable in a highly specific manner by Watson-Crick hybridization. The resulting DNA-protein conjugates can be advantageously used in a variety of applications, ranging from biomedical diagnostics to DNA-based nanofabrication. This critical review provides an overview on chemical approaches to the synthesis of DNA-protein conjugates and their applications in biomolecular nanosciences (96 references). PMID- 21975574 TI - Anti-"negative-doping" testing: a new perspective in anti-doping research? PMID- 21975575 TI - Measurement of Power in Selectorized Strength Training Equipment. AB - We derived the exact analytical expression of the instantaneous joint power in exercises with single-joint, variable-resistance, selectorized strength-training equipment, taking into account all the relevant geometric, kinematic and dynamic variables of both the movable equipment elements (resistance input lever, cam pulley system, weight stack) and of the user's exercising limb. A numerical algorithm was also designed to express, in the presence of a cam, the rectilinear kinematic variables of the weight stack as a function of the rotational kinematic variables of the resistance input lever, and vice versa. Given that information, one can measure the value of the instantaneous and mean joint power exclusively by means of a linear encoder placed on the weight stack or, alternatively, only by the use of an angular encoder placed on the rotational axis of the resistance lever. The results highlight that, for knee extension exercises with leg extension equipment, the real values of both instantaneous and mean joint power may differ by more than 50% in comparison with the values obtained by taking into account only the mass and velocity of the weight stack. These differences are notable not only in explosive exercises, but whenever considerable joint velocities/accelerations occur within the range of motion. PMID- 21975576 TI - Incidental computed tomography sacroiliitis: clinical significance and inappropriateness of the New York radiological grading criteria for the diagnosis. AB - The clinical implications of computed tomography (CT) detected sacroiliac joint (SIJ) changes compatible with sacroiliitis has been rarely discussed in the literature. The aim of the present study was to describe prevalence and clinical correlations of sacroiliitis, noted incidentally by abdominal CT in patients referred for non-musculoskeletal complaints, utilizing the New York radiological grading criteria for reference. Five hundred ninety-eight CT scans of the abdomen of patients 18-55 years old, performed at a community medical center, were prospectively examined for the presence of imaging changes consistent with sacroiliitis. Patients with the evidence of bilateral sacroiliitis of grade >=2 were interviewed and underwent a rheumatologic examination. Twenty-two patients (13 females) were enrolled. Only eight patients (six males) had a history and clinical picture compatible with previously undiagnosed axial spondyloarthritis (SpA). Only the presence of erosions/joint space irregularity and/or inhomogeneous osseous sclerosis around SIJs on CT correlated with the clinical diagnosis of axial SpA. Dense homogenous osseous sclerosis was unrelated to axial SpA and was seen almost exclusively in females. The prevalence of incidental CT sacroiliitis is low, while the New York radiological grading criteria for diagnosing sacroiliitis may be inappropriate for CT imaging. CT noted erosions of the SIJ appear to be a reliable diagnostic sign of sacroiliitis, while the significance of the osseous sclerosis, seen on CT adjacent to SIJs requires better understanding. PMID- 21975577 TI - Visual observation of the mercury-stimulated peroxidase mimetic activity of gold nanoparticles. AB - Mercury-stimulated peroxidase mimetic activity of gold nanoparticles was presented, with which a sensitive label-free colorimetric method for Hg(2+) was developed. PMID- 21975578 TI - Partial Response and Cardiovascular Recovery after Sorafenib Dose Reduction in a Multinodular HCC Patient. PMID- 21975580 TI - Neurophysiological functioning of occasional and heavy cannabis users during THC intoxication. AB - RATIONALE: Experienced cannabis users demonstrate tolerance to some of the impairing acute effects of cannabis. OBJECTIVES: The present study investigates whether event-related potentials (ERPs) differ between occasional and heavy cannabis users after acute Delta9-tetrahydrocannabinol (THC) administration, as a result of tolerance. METHODS: Twelve occasional and 12 heavy cannabis users participated in a double-blind, placebo-controlled, crossover study. On two separate days, they smoked a joint containing 0 or 500 MUg/kg body weight THC. ERPs were measured while subjects performed a divided attention task (DAT) and stop signal task (SST). RESULTS: In the DAT, THC significantly decreased P100 amplitude in occasional but not in heavy cannabis users. P300 amplitude in the DAT was significantly decreased by THC in both groups. The N200 peak in the SST was not affected by treatment in neither of the groups. Performance in the SST was impaired in both groups after THC treatment, whereas performance in the DAT was impaired by THC only in the occasional users group. CONCLUSIONS: The present study confirms that heavy cannabis users develop tolerance to some of the impairing behavioral effects of cannabis. This tolerance was also evident in the underlying ERPs, suggesting that tolerance demonstrated on performance level is not (completely) due to behavioral compensation. PMID- 21975581 TI - An International Survey-based Algorithm for the Pharmacologic Treatment of Chorea in Huntington's Disease. AB - It is generally believed that treatments are available to manage chorea in Huntington's disease (HD). However, lack of evidence prevents the establishment of treatment guidelines. The HD chorea research literature fails to address the indications for drug treatment, drug selection, drug dosing and side effect profiles, management of inadequate response to a single drug, and preferred drug when behavioral symptoms comorbid to chorea are present. Because there is lack of an evidence base to inform clinical decision-making, we surveyed an international group of experts to address these points. Survey results showed that patient stigma, physical injury, gait instability, work interference, and disturbed sleep were indications for a drug treatment trial. However, the experts did not agree on first choice of chorea drug, with the majority of experts in Europe favoring an antipsychotic drug (APD), and a near equal split in first choice between an APD and tetrabenazine (TBZ) among experts from North America and Australia. All experts chose an APD when comorbid psychotic or aggressive behaviors were present, or when active depression prevented the use of TBZ. However, there was agreement from all geographic regions that both APDs and TBZ were acceptable as monotherapy in other situations. Perceived efficacy and side effect profiles were similar for APDs and TBZ, except for depression as a significant side effect of TBZ. Experts used a combination of an APD and TBZ when treatment required both drugs for control of chorea and a concurrent comorbid symptom, or when severe chorea was inadequately controlled by either drug alone. The benzodiazepines (BZDs) were judged ineffective as monotherapy but useful as adjunctive therapy, particularly when chorea was exacerbated by anxiety. There was broad disagreement about the use of amantadine for chorea. Experts who had used amantadine described its benefit as small and transient. In addition to survey results, this report reviews available chorea studies, and lastly presents an algorithm for the treatment of chorea in HD which is based on expert preferences obtained through this international survey. PMID- 21975582 TI - Important work of this skilled group of maternity nurses. PMID- 21975584 TI - Quantitative analysis of nanoparticle growth through plasmonics. AB - Plasmon excitation appears to be a powerful and flexible tool for probing in situ and in real time the growth of supported conducting metal nanoparticles. However, although models exist for analysing optical profiles, limitations arise in the realistic modelling of particle shape from the lack of knowledge of temperature effects and of broadening sources. This paper reports on the growth of silver on alumina at 190-675 K monitored by surface differential reflectivity spectroscopy in the UV-visible range. In the framework of plasmonic response analysis, particles are modelled by truncated spheres. Their polarizabilities are computed within the quasi-static approximation and used as an input to the interface susceptibilities model in order to determine the Fresnel reflection coefficient. The pivotal importance of the thermal variation of the metal dielectric constant is demonstrated. Finite-size effects are accounted for. As size distribution fluctuations contribute marginally to the lineshape compared to the aspect ratio (diameter/height) distribution, a convolution method for representing the experimental broadening is introduced. Effects of disorder on the lineshape are discussed. It is highlighted that beside the quality of the fit (not a proof by itself!), physical meaning of the parameters related to the sticking probability, growth and wetting is crucially required for validating models. The proposed modelling opens interesting perspectives for the quantitative study of growth via plasmonics, in particular in the case of noble metals. PMID- 21975583 TI - Development of an improved methodology to detect infectious airborne influenza virus using the NIOSH bioaerosol sampler. AB - A unique two-stage cyclone bioaerosol sampler has been developed at NIOSH that can separate aerosols into three size fractions. The ability of this sampler to collect infectious airborne viruses from a calm-air chamber loaded with influenza A virus was tested. The sampler's efficiency at collecting aerosolized viral particles from a calm-air chamber is essentially the same as that from the high performance SKC BioSampler that collects un-fractionated particles directly into a liquid media (2.4 * 10(4) total viral particles per liter of sampled air (TVP/L) versus 2.6 * 10(4) TVP/L, respectively, after 15 min) and the efficiency is relatively constant over collection times of 15, 30 and 60 min. Approximately 34% of the aerosolized infectious virus collected after 15 min with the NIOSH bioaerosol sampler remained infectious, and infectious virus was found in all three size fractions. After 60 min of sampling, the infectious virus/liter air found in the NIOSH bioaerosol sampler was 15% of that found in the SKC BioSampler. This preservation of infectivity by the NIOSH bioaerosol sampler was maintained even when the initial infectivity prior to aerosolization was as low as 0.06%. The utility of the NIOSH bioaerosol sampler was further extended by incorporating an enhanced infectivity detection methodology developed in our laboratory, the viral replication assay, which amplified the infectious virus making it more readily detectable. PMID- 21975585 TI - Brain. Editorial. PMID- 21975586 TI - Electroencephalographic source imaging: a prospective study of 152 operated epileptic patients. AB - Electroencephalography is mandatory to determine the epilepsy syndrome. However, for the precise localization of the irritative zone in patients with focal epilepsy, costly and sometimes cumbersome imaging techniques are used. Recent small studies using electric source imaging suggest that electroencephalography itself could be used to localize the focus. However, a large prospective validation study is missing. This study presents a cohort of 152 operated patients where electric source imaging was applied as part of the pre-surgical work-up allowing a comparison with the results from other methods. Patients (n = 152) with >1 year postoperative follow-up were studied prospectively. The sensitivity and specificity of each imaging method was defined by comparing the localization of the source maximum with the resected zone and surgical outcome. Electric source imaging had a sensitivity of 84% and a specificity of 88% if the electroencephalogram was recorded with a large number of electrodes (128-256 channels) and the individual magnetic resonance image was used as head model. These values compared favourably with those of structural magnetic resonance imaging (76% sensitivity, 53% specificity), positron emission tomography (69% sensitivity, 44% specificity) and ictal/interictal single-photon emission computed tomography (58% sensitivity, 47% specificity). The sensitivity and specificity of electric source imaging decreased to 57% and 59%, respectively, with low number of electrodes (<32 channels) and a template head model. This study demonstrated the validity and clinical utility of electric source imaging in a large prospective study. Given the low cost and high flexibility of electroencephalographic systems even with high channel counts, we conclude that electric source imaging is a highly valuable tool in pre-surgical epilepsy evaluation. PMID- 21975587 TI - Imaging the seizure onset zone with stereo-electroencephalography. AB - Stereo-electroencephalography is used to localize the seizure onset zone and connected neuronal networks in surgical candidates suffering from intractable focal epilepsy. The concept of an epileptogenicity index has been proposed recently to represent the likelihood of various regions being part of the seizure onset zone. It quantifies low-voltage fast activity, the electrophysiological signature of seizure onset usually assessed visually by neurologists. Here, we revisit epileptogenicity in light of neuroimaging tools such as those provided in statistical parametric mapping software. Our goal is to propose a robust approach, allowing easy exploration of patients' brains in time and space. The procedure is based upon statistical parametric mapping, which is an established framework for comparing multi-dimensional image data that allows one to correct for inherent multiple comparisons. Statistics can also be performed at the group level, between seizures in the same patient or between patients suffering from the same type of epilepsy using normalization of brains to a common anatomic atlas. Results are obtained from three case studies (insular reflex epilepsy, cryptogenic frontal epilepsy and lesional occipital epilepsy) where tailored resection was performed, and from a group of 10 patients suffering from mesial temporal lobe epilepsy. They illustrate the basics of the technique and demonstrate its very good reproducibility and specificity. Most importantly, the proposed approach to the quantification of the seizure onset zone allows one to summarize complex signals in terms of a time-series of statistical parametric maps that can support clinical decisions. Quantitative neuroimaging of stereo electroencephalographic features of seizures might thus help to provide better pre-surgical assessment of patients undergoing resective surgery. PMID- 21975588 TI - Altered functional-structural coupling of large-scale brain networks in idiopathic generalized epilepsy. AB - The human brain is a large-scale integrated network in the functional and structural domain. Graph theoretical analysis provides a novel framework for analysing such complex networks. While previous neuroimaging studies have uncovered abnormalities in several specific brain networks in patients with idiopathic generalized epilepsy characterized by tonic-clonic seizures, little is known about changes in whole-brain functional and structural connectivity networks. Regarding functional and structural connectivity, networks are intimately related and share common small-world topological features. We predict that patients with idiopathic generalized epilepsy would exhibit a decoupling between functional and structural networks. In this study, 26 patients with idiopathic generalized epilepsy characterized by tonic-clonic seizures and 26 age and sex-matched healthy controls were recruited. Resting-state functional magnetic resonance imaging signal correlations and diffusion tensor image tractography were used to generate functional and structural connectivity networks. Graph theoretical analysis revealed that the patients lost optimal topological organization in both functional and structural connectivity networks. Moreover, the patients showed significant increases in nodal topological characteristics in several cortical and subcortical regions, including mesial frontal cortex, putamen, thalamus and amygdala relative to controls, supporting the hypothesis that regions playing important roles in the pathogenesis of epilepsy may display abnormal hub properties in network analysis. Relative to controls, patients showed further decreases in nodal topological characteristics in areas of the default mode network, such as the posterior cingulate gyrus and inferior temporal gyrus. Most importantly, the degree of coupling between functional and structural connectivity networks was decreased, and exhibited a negative correlation with epilepsy duration in patients. Our findings suggest that the decoupling of functional and structural connectivity may reflect the progress of long-term impairment in idiopathic generalized epilepsy, and may be used as a potential biomarker to detect subtle brain abnormalities in epilepsy. Overall, our results demonstrate for the first time that idiopathic generalized epilepsy is reflected in a disrupted topological organization in large-scale brain functional and structural networks, thus providing valuable information for better understanding the pathophysiological mechanisms of generalized tonic clonic seizures. PMID- 21975589 TI - Gelastic epilepsy and hypothalamic hamartomas: neuroanatomical analysis of brain lesions in 100 patients. AB - Hypothalamic hamartomas present with isolated fits of ictal laughter (gelastic epilepsy) or a combination of gelastic and other types of seizures. Many of these patients also suffer from cognitive decline, neuropsychiatric comorbidities and precocious puberty. Although there is a large body of anecdotal evidence about hypothalamic hamartomas and gelastic seizures, many questions still remain to be answered. For instance, which specific hypothalamic regions are most affected by the location of hamartomas causing laughing versus other types of seizures? Does the neuroanatomical localization of the lesions differ in cases with only gelastic seizures or a combination of gelastic and other types of seizures? Does the location of the lesions correlate with the presence of precocious puberty, and does the type of lesion influence the severity or the type of seizures? In a retrospective review of clinical and structural neuroimaging data from 100 cases of gelastic epilepsy and hypothalamic hamartoma, we aimed to address these questions by analysing the clinical presentation and the neuroanatomical features of the hypothalamic lesions in these patients. Our findings suggest that in all 100 cases, lesions were centred at the level of the mammillary bodies in the posterior hypothalamus. Compared with the patients with pure gelastic seizures (n = 32), those with gelastic and other types of seizures (n = 68) had significantly longer duration of epilepsy (P < 0.001), whereas age of seizure onset, the volume of lesions and the proximity to the mammillary bodies were not different between the two groups. In contrast, patients with cognitive or developmental impairment and those with precocious puberty had significantly larger lesions involving the anterior and posterior hypothalamus. PMID- 21975590 TI - The neural correlates of inner speech defined by voxel-based lesion-symptom mapping. AB - The neural correlates of inner speech have been investigated previously using functional imaging. However, methodological and other limitations have so far precluded a clear description of the neural anatomy of inner speech and its relation to overt speech. Specifically, studies that examine only inner speech often fail to control for subjects' behaviour in the scanner and therefore cannot determine the relation between inner and overt speech. Functional imaging studies comparing inner and overt speech have not produced replicable results and some have similar methodological caveats as studies looking only at inner speech. Lesion analysis can avoid the methodological pitfalls associated with using inner and overt speech in functional imaging studies, while at the same time providing important data about the neural correlates essential for the specific function. Despite its advantages, a study of the neural correlates of inner speech using lesion analysis has not been carried out before. In this study, 17 patients with chronic post-stroke aphasia performed inner speech tasks (rhyme and homophone judgements), and overt speech tasks (reading aloud). The relationship between brain structure and language ability was studied using voxel-based lesion-symptom mapping. This showed that inner speech abilities were affected by lesions to the left pars opercularis in the inferior frontal gyrus and to the white matter adjacent to the left supramarginal gyrus, over and above overt speech production and working memory. These results suggest that inner speech cannot be assumed to be simply overt speech without a motor component. It also suggests that the use of overt speech to understand inner speech and vice versa might result in misleading conclusions, both in imaging studies and clinical practice. PMID- 21975591 TI - Process and progress: John Hughlings Jackson's philosophy of science. AB - Some scepticism has been voiced over whether the work of John Hughlings Jackson possesses any significant philosophical orientation. This article argues that Hughlings Jackson was acquainted with the work of a wide range of philosophers. In particular, certain aspects of the writings of John Stuart Mill are reflected in Hughlings Jackson's own work. From early in his career, Hughlings Jackson adopted a critical stance in his neurological papers, seeking to expose shortcomings in the conventional practices of his peers and urging greater methodological rigour and sophistication in order to advance their science. This critical and 'procedurist' bias endows Hughlings Jackson's writings with a characteristically modern character. PMID- 21975592 TI - Closed reduction and percutaneous fixation of sacroiliac luxations in cats using 2.4 mm cannulated screws - a cadaveric study. AB - OBJECTIVES: To describe fluoroscopically assisted percutaneous placement of 2.4 mm cannulated screws for fixation of artificially induced sacroiliac luxations in cats, and to evaluate the success of this technique in restoration of normal pelvic anatomy. METHODS: Fluoroscopically assisted closed reduction and percutaneous fixation of sacro-iliac luxations using 2.4 mm cannulated screws was performed in cadavers of 12 cats. Pre- and postoperative radiographs and postoperative computed tomographic scans were used to evaluate screw placement, screw purchase within the sacral body, reduction of the sacroiliac joint, pelvic canal diameter ratio, and hemipelvic canal width ratio. RESULTS: Mean total surgical time was 6 minutes and 10 seconds +/- 53 seconds and mean total time of fluoroscopic screening for each procedure was 44 seconds +/- 6 seconds. Mean percent of reduction was 98.33% and mean screw purchase within the sacral body was 73%. Eleven out of 12 screws were placed in a satisfactory location in the sacral body. Pelvic canal diameter ratio and hemipelvic canal width ratio indicated successful restoration of the pelvic anatomy. CLINICAL SIGNIFICANCE: Our results confirm that fluoroscopically assisted percutaneous placement of 2.4 mm cannulated screws is a feasible technique for fixation of sacroiliac luxations in cats. Mechanical properties of this fixation technique need to be evaluated before the use in clinical patients. PMID- 21975593 TI - Effect of a dissonance-based prevention program on risk for eating disorder onset in the context of eating disorder risk factors. AB - Test (a) whether a dissonance-based eating disorder prevention program that reduces thin-ideal internalization mitigates the effects of risk factors for eating disorder onset and (b) whether the risk factors moderate the effects of this intervention on risk for eating disorder onset, to place the effects of this intervention within the context of established risk factors. Female adolescents (N=481) with body image concerns were randomized to the dissonance-based program, healthy weight control program, expressive writing control condition, or assessment-only control condition. Denial of costs of pursuing the thin-ideal was the most potent risk factor for eating disorder onset during the 3-year follow-up (OR=5.0). The dissonance program mitigated the effect of this risk factor. For participants who did not deny costs of pursuing the thin-ideal, emotional eating and externalizing symptoms increased risk for eating disorder onset. Negative affect attenuated the effects of each of the active interventions in this trial. Results imply that this brief prevention program offsets the risk conveyed by the most potent risk factor for eating disorder onset in this sample, implicate three vulnerability pathways to eating pathology involving thin-ideal pursuit, emotional eating, and externalizing symptoms, and suggest that negative affect mitigates the effects of eating disorder prevention programs. PMID- 21975595 TI - A generalized probe selection method for DNA chips. AB - The flaws in the present probe selection methods restrained the development of the DNA chip technology and its applications. The presented generalized probe selection method for the DNA chips elaborates the length of the probe, the melting temperatures, the specificity of the probe, and the position where the probe may bind to the targets. PMID- 21975594 TI - Altered expression of tight junction proteins in mammary epithelium after discontinued suckling in mice. AB - Milk production is modulated by the paracellular barrier function of tight junction (TJ) proteins located in the mammary epithelium. The aim of our study was the molecular analysis of TJs in native lactating murine mammary gland epithelium as this process may strongly challenge epithelial barrier properties and regulation. Mammary gland tissue specimens from lactating control mice and animals after a 20-h interruption of suckling were prepared; histological analyses were performed by light and electron microscopy; and expression of TJ proteins was detected by PCR, Western blotting, immunofluorescent staining, and confocal laser scanning microscopy. Discontinuation of suckling resulted in a substantial accumulation of milk in mammary glands, an increase of alveolar size, and a flattening of epithelial cells without effects on inflammatory indicators. In control tissues, PCR and Western blots showed signals for occludin, and claudin-1, -2, -3, -4, -5, -7, -8, -15, and -16. After a 20-h accumulation of milk, expression of two sealing TJ proteins, claudin-1 and -3, was markedly increased, whereas two TJ proteins involved in cation transport, claudin-2 and 16, were reduced. Real-time PCR validated increased transcripts of claudin-1 and claudin-3. During extension of mammary glands in the process of lactation, claudin-1 and -3 are markedly induced and claudin-2 and -16 are decreased. Volume and composition of milk might be strongly dependent on this counter-regulation of sealing claudins with permeability-mediating claudins, indicating a physiological process of a tightening of TJs against a back-leak of solutes and ions from the alveolar lumen. PMID- 21975596 TI - Seasonal Synechococcus and Thaumarchaeal population dynamics examined with high resolution with remote in situ instrumentation. AB - Monterey Bay, CA is an Eastern boundary upwelling system that is nitrogen limited much of the year. In order to resolve population dynamics of microorganisms important for nutrient cycling in this region, we deployed the Environmental Sample Processor with quantitative PCR assays targeting both ribosomal RNA genes and functional genes for subclades of cyanobacteria (Synechococcus) and ammonia oxidizing Archaea (Thaumarchaeota) populations. Results showed a strong correlation between Thaumarchaea abundances and nitrate during the spring upwelling but not the fall sampling period. In relatively stratified fall waters, the Thaumarchaeota community reached higher numbers than in the spring, and an unexpected positive correlation with chlorophyll concentration was observed. Further, we detected drops in Synechococcus abundance that occurred on short (that is, daily) time scales. Upwelling intensity and blooms of eukaryotic phytoplankton strongly influenced Synechococcus distributions in the spring and fall, revealing what appear to be the environmental limitations of Synechococcus populations in this region. Each of these findings has implications for Monterey Bay biogeochemistry. High-resolution sampling provides a better-resolved framework within which to observe changes in the plankton community. We conclude that controls on these ecosystems change on smaller scales than are routinely assessed, and that more predictable trends will be uncovered if they are evaluated within seasonal (monthly), rather than on annual or interannual scales. PMID- 21975597 TI - Massive multiplication of genome and ribosomes in dormant cells (akinetes) of Aphanizomenon ovalisporum (Cyanobacteria). AB - Akinetes are dormancy cells commonly found among filamentous cyanobacteria, many of which are toxic and/or nuisance, bloom-forming species. Development of akinetes from vegetative cells is a process that involves morphological and biochemical modifications. Here, we applied a single-cell approach to quantify genome and ribosome content of akinetes and vegetative cells in Aphanizomenon ovalisporum (Cyanobacteria). Vegetative cells of A. ovalisporum were naturally polyploid and contained, on average, eight genome copies per cell. However, the chromosomal content of akinetes increased up to 450 copies, with an average value of 119 genome copies per akinete, 15-fold higher than that in vegetative cells. On the basis of fluorescence in situ hybridization, with a probe targeting 16S rRNA, and detection with confocal laser scanning microscopy, we conclude that ribosomes accumulated in akinetes to a higher level than that found in vegetative cells. We further present evidence that this massive accumulation of nucleic acids in akinetes is likely supported by phosphate supplied from inorganic polyphosphate bodies that were abundantly present in vegetative cells, but notably absent from akinetes. These results are interpreted in the context of cellular investments for proliferation following a long-term dormancy, as the high nucleic acid content would provide the basis for extended survival, rapid resumption of metabolic activity and cell division upon germination. PMID- 21975599 TI - Walk as directed! Adolescents' adherence to pedometer intervention protocol. AB - BACKGROUND: Despite frequent use of pedometers in interventions targeting youth PA, there is no literature that addresses the prevalence and reasons for protocol nonadherence. METHODS: Adherence behaviors of early adolescents (n = 43; Meanage = 12.3 +/- 1.0) in an 8-week, faith-based intervention were monitored/recorded. Students provided reasons for various aspects of protocol breach, which were used to develop a post intervention questionnaire. Analyses included calculations of frequency/percentage as well as cross tabulations/chi square to detect gender/age differences. RESULTS: Over the intervention, recording PA in logs decreased by 85% and was attributed to forgetfulness and lack of time. For pedometers, highest frequency events included error codes (n = 501), incorrect wear (37%, >= 1 day), and shaking (58%-69%, >= 1 time). Top reasons for shaking were to make up for lost step opportunities and get further along the route. Of permissible stepping strategies, males used ambulatory activity on the playground and stair usage more, while 6th graders used speed stepping in place more than their respective counterparts. CONCLUSIONS: Students admit to basal levels of nonadherence, which should be taken into consideration when designing/implementing interventions. Integrating intervention tasks into the regular curriculum and providing sufficient opportunities to perform them may alleviate some barriers to adherence. Future research should attempt to confirm results in other school types/levels as well as quantify these behaviors in free-living or unstructured settings. PMID- 21975598 TI - Diversity and dynamics of rare and of resident bacterial populations in coastal sands. AB - Coastal sands filter and accumulate organic and inorganic materials from the terrestrial and marine environment, and thus provide a high diversity of microbial niches. Sands of temperate climate zones represent a temporally and spatially highly dynamic marine environment characterized by strong physical mixing and seasonal variation. Yet little is known about the temporal fluctuations of resident and rare members of bacterial communities in this environment. By combining community fingerprinting via pyrosequencing of ribosomal genes with the characterization of multiple environmental parameters, we disentangled the effects of seasonality, environmental heterogeneity, sediment depth and biogeochemical gradients on the fluctuations of bacterial communities of marine sands. Surprisingly, only 3-5% of all bacterial types of a given depth zone were present at all times, but 50-80% of them belonged to the most abundant types in the data set. About 60-70% of the bacterial types consisted of tag sequences occurring only once over a period of 1 year. Most members of the rare biosphere did not become abundant at any time or at any sediment depth, but varied significantly with environmental parameters associated with nutritional stress. Despite the large proportion and turnover of rare organisms, the overall community patterns were driven by deterministic relationships associated with seasonal fluctuations in key biogeochemical parameters related to primary productivity. The maintenance of major biogeochemical functions throughout the observation period suggests that the small proportion of resident bacterial types in sands perform the key biogeochemical processes, with minimal effects from the rare fraction of the communities. PMID- 21975600 TI - Real-time monitoring of the aging of single plasmonic copper nanoparticles. AB - We demonstrate that the continuous real-time monitoring of the growth and surface oxidation process of single Cu nanoparticles (NPs) on an indium-tin oxide (ITO) substrate by dark-field microscopy (DFM) and plasmon resonance Rayleigh scattering (PRRS) spectroscopy is possible. PMID- 21975602 TI - Fluorescence polarization biosensor based on an aptamer enzymatic cleavage protection strategy. AB - A novel fluorescence polarization (FP) aptasensing platform based on target induced aptamer enzymatic cleavage protection is reported. The method relies on the FP analysis of the phosphodiesterase I mediated size variation of a dye labeled aptamer. The tyrosinamide/antityrosinamide DNA aptamer couple was firstly tested as a model system to establish the proof-of-concept. In the absence of the target, the labeled aptamer was enzymatically cleaved into small DNA fragments, leading to a low FP signal. Upon tyrosinamide binding, the DNA substrate was partially protected against the enzymatic attack, leading to an increase in the fluorescence anisotropy response as a result of the higher average molecular volume of the weakly digested probe. The method was subsequently applied to two other systems, i.e., for the detection of ochratoxin A and adenosine. Such an approach was found to combine simplicity and general applicability features. PMID- 21975603 TI - Nanoparticle encapsulated silver carbene complexes and their antimicrobial and anticancer properties: a perspective. AB - This perspective discusses the uses of silver for both antimicrobial and anticancer applications. It focuses on the synthesis of silver N-heterocyclic carbene complexes (SCCs) and their in vitro efficacy against a broad spectrum of bacteria, as well as their antitumor properties. Finally, different polymeric nanoparticles are discussed as delivery vehicles for the encapsulation of SCCs and other therapeutic agents for use in vivo. PMID- 21975604 TI - Occurrence of antibiotic resistance and characterization of resistance genes and integrons in Enterobacteriaceae isolated from integrated fish farms in South China. AB - Antibiotics are still widely applied in animal husbandry to prevent diseases and used as feed additives to promote animal growth. This could result in antibiotic resistance to bacteria and antibiotic residues in animals. In this paper, Enterobacteriaceae isolated from four integrated fish farms in Zhongshan, South China were tested for antibiotic resistance, tetracycline resistance genes, sulfonamide resistance genes, and class 1 integrons. The Kirby-Bauer disk diffusion method and polymerase chain reaction (PCR) assays were carried out to test antibiotic susceptibility and resistance genes, respectively. Relatively high antibiotic resistance frequencies were found, especially for ampicillin (80%), tetracycline (52%), and trimethoprim (50%). Out of 203 Enterobacteriaceae isolates, 98.5% were resistant to one or more antibiotics tested. Multiple antibiotic resistance (MAR) was found highest in animal manures with a MAR index of 0.56. Tetracycline resistance genes (tet(A), tet(C)) and sulfonamide resistance genes (sul2) were detected in more than 50% of the isolates. The intI1 gene was found in 170 isolates (83.7%). Both classic and non-classic class 1 integrons were found. Four genes, aadA5, aadA22, dfr2, and dfrA17, were detected. To our knowledge, this is the first report for molecular characterization of antibiotic resistance genes in Enterobacteriaceae isolated from integrated fish farms in China and the first time that gene cassette array dfrA17-aadA5 has been detected in such fish farms. Results of this study indicated that fish farms may be a reservoir of highly diverse and abundant antibiotic resistant genes and gene cassettes. Integrons may play a key role in multiple antibiotic resistances posing potential health risks to the general public and aquaculture. PMID- 21975601 TI - STC1 induction by PACAP is mediated through cAMP and ERK1/2 but not PKA in cultured cortical neurons. AB - The neuroprotective actions of PACAP (pituitary adenylate cyclase-activating polypeptide) in vitro and in vivo suggest that activation of its cognate G protein coupled receptor PAC1 or downstream signaling molecules,and thus activation of PACAP target genes, could be of therapeutic benefit. Here, we show that cultured rat cortical neurons predominantly expressed the PAC1hop and null variants. PACAP receptor activation resulted in the elevation of the two second messengers cAMP and Ca(2+) and expression of the putative neuroprotectant stanniocalcin 1(STC1). PACAP signaling to the STC1 gene proceeded through the extracellular signal-regulated kinases 1 and 2(ERK1/2), but not through the cAMP dependent protein kinase (PKA), and was mimicked by the adenylate cyclase activator forskolin. PACAP- and forskolin-mediated activation of ERK1/2 occurred through cAMP, but not PKA.These results suggest that STC1 gene induction proceeds through cAMP and ERK1/2, independently of PKA, the canonical cAMP effector. In contrast, PACAP signaling to the BDNF gene proceeded through PKA, suggesting that two different neuroprotective cAMP pathways co-exist in differentiated cortical neurons. The selective activation of a potentially neuroprotective cAMP-dependent pathway different from the canonical cAMP pathway used in many physiological processes, such as memory storage, has implications for pharmacological activation of neuroprotection in vivo. PMID- 21975605 TI - Comparison of mortality between nosocomial and community-acquired febrile neutropenia patients treated initially with cefazolin plus tobramycin: retrospective chart review. AB - Cefazolin plus tobramycin have been determined to be effective for community acquired FN, but have not been evaluated in the treatment of nosocomial FN. This study compared the incidence of mortality from 2002 to 2004 with 2008 to 2009 in patients with nosocomial FN treated with cefazolin plus tobramycin and compared characteristics of patients with nosocomially acquired FN to community acquired FN. A retrospective chart review of 45 nosocomial FN episodes from 2008 to 2009, and 54 episodes from 2002 to 2004 treated with cefazolin plus tobramycin was conducted. Data on the community acquired FN episodes was obtained from our previous research. Nosocomial FN mortality increased from 4% in 2002-2004 to 13% in 2008-2009 (p = 0.08). The nosocomial cohort was at higher risk of medical complications and mortality than the community-acquired cohort based on several variables (neutrophil nadir, duration of neutropenia and fever, hematological malignancy, MASCC and Talcott score; p < 0.05). As a result, the nosocomial cohort was treated with longer courses of antibiotic therapy (14 days vs 7 days; p < 0.0001) and were more likely to require broader spectrum antibiotics (64 out of 99 vs 34 out of 96; p < 0.0001). There was an observed increased risk of mortality from 2002 to 2004 compared with 2008 to 2009 in patients treated with cefazolin plus tobramycin for nosocomial FN, this was notable despite not attaining statistical significance. Therefore, this regimen is not appropriate for nosocomial FN. PMID- 21975606 TI - The impact of psychiatric comorbidity on quality of life in patients undergoing herniated disc surgery. AB - BACKGROUND: Recent studies examined the role of psychiatric comorbidity in the process of rehabilitation in patients undergoing herniated disc surgery. These patients suffer from physical and psychosocial complaints or symptoms, which impact their everyday life negatively and the success of rehabilitation potentially. The objectives of this study are (1) to examine the quality of life (QoL) in disc surgery patients and to compare the findings with reference data from the general German population, and (2) to investigate the impact of psychiatric comorbidity on QoL of patients undergoing herniated disc surgery. METHODS: This study consists of 305 patients aged between 18 and 55 years who took part in face-to-face interviews during their hospital stay. Psychiatric comorbidity was assessed with the Composite International Diagnostic Interview (CIDI-DIA-X). By means of the 36-Item Short-Form Health Survey (SF-36), QoL was assessed in patients undergoing herniated disc surgery with and without psychiatric comorbidity. These findings were compared with the QoL of a representative sample of the general German population. RESULTS: Compared with the general population, QoL in patients with herniated disc surgery was lower in all domains of the SF-36. Psychiatric comorbidity impacts the QoL in patients with herniated disc surgery in all SF-36 domains except "physical function". The patients with psychiatric comorbidity showed significantly lower levels of QoL in the domains "bodily pain", "vitality", "social function", "role emotional", and "mental health". CONCLUSIONS: Psychiatric comorbidity has a substantial adverse effect on QoL in patients undergoing disc surgery. Therefore, it will be necessary to diagnose psychiatric comorbidities at an early stage and to include psychosocial interventions in the treatment of herniated disc patients aimed at improving deficits in psychosocial functioning and QoL. PMID- 21975607 TI - Periodic magnetoresistance oscillations induced by superconducting vortices in single crystal Au nanowires. AB - We show in this paper that it is possible to induce superconducting vortices in a gold nanowire connected to superconducting electrodes. The gold nanowire acquires superconductivity by the proximity effect. The differential magnetoresistance of the nanowire beyond a critical magnetic field shows uniform oscillations with increasing field with a period of Phi(0)/(2pir(2)) (Phi(0) = h/2e is the superconducting flux quantum, r = 35 nm is the radius of the nanowire). Our analysis indicates that these periodic oscillations are the signatures of the sequential generation and moving of vortices across the gold nanowire. PMID- 21975609 TI - Beyond must: supporting the evolving role of the designated institutional official. PMID- 21975612 TI - The direct, indirect, and intangible benefits of graduate medical education programs to their sponsoring institutions and communities. AB - Declining reimbursement for graduate medical education (GME) as well as increasing hospital competition has placed the cost of GME in the spotlight of institutional administrators. Traditional hospital-generated cost center profit and loss statements fail to accurately reflect the full economic impact of training programs on the institution as well as the larger community. A more complete analysis would take into consideration the direct, indirect, and "intangible" benefits of GME programs. The GME programs usually have a favorable impact on the trainees themselves, the sponsoring institution, the local community, university sponsors and affiliates, and the greater community, and all of these areas need to be considered in the economic analysis. Complete analyses of programs often demonstrate very positive benefits to their sponsoring institutions that would not be recognized on simple cost center profit and loss reports. Studies in the literature that quantify the net economic benefits of GME programs are consistent in their favorable findings. PMID- 21975613 TI - Use of an institutional template for annual program evaluation and improvement: benefits for program participation and performance. AB - PURPOSE: The Accreditation Council for Graduate Medical Education (ACGME) expects programs to engage in ongoing, meaningful improvement, facilitated in part through an annual process of program assessment and improvement. The Duke University Hospital Office of Graduate Medical Education (OGME) used an institutional practice-based learning and improvement strategy to improve the annual evaluation and improvement of its programs. METHODS: The OGME implemented several strategies including the development and dissemination of a template for the report, program director and coordinator development, a reminder and tracking system, incorporation of the document into internal reviews, and use of incentives to promote program adherence. RESULTS: In the first year of implementation (summer 2005), 27 programs (37%) submitted documentation of their annual program evaluation and improvement to the OGME; this increased to 100% of programs by 2009. A growing number of programs elected to use the template in lieu of written minutes. The number of citations related to required program review and improvement decreased from 12 in a single academic year to 3 over the last 5 years. CONCLUSION: Duke University Hospital's institutional initiative to incorporate practice-based learning and improvement resulted in increased documentation, greater use of a standardized template, fewer ACGME-related citations, and enhanced consistency in preparing for ACGME site visits. PMID- 21975614 TI - Use of the kalamazoo essential elements communication checklist (adapted) in an institutional interpersonal and communication skills curriculum. AB - BACKGROUND: This study examined the psychometric properties of the Kalamazoo Essential Elements Communication Checklist (Adapted) (KEECC-A), which addresses 7 key elements of physician communication identified in the Kalamazoo Consensus Statement, in a sample of 135 residents in multiple specialties at a large urban medical center in 2008-2009. The KEECC-A was used by residents, standardized patients, and faculty as the assessment tool in a broader institutional curriculum initiative. METHODS: Three separate KEECC-A scores (self-ratings, faculty ratings, and standardized patient ratings) were calculated for each resident to assess the internal consistency and factor structure of the checklist. In addition, we analyzed KEECC-A ratings by gender and US versus international medical graduates, and collected American Board of Internal Medicine Patient Satisfaction Questionnaire (PSQ) scores for a subsample of internal medicine residents (n = 28) to examine the relationship between this measure and the KEECC-A ratings to provide evidence of convergent validity. RESULTS: The KEECC-A ratings generated by faculty, standardized patients, and the residents themselves demonstrated a high degree of internal consistency. Factor analyses of the 3 different sets of KEECC-A ratings produced a consistent single factor structure. We could not examine the relationship between KEECC-A and the PSQ because of substantial range restriction in PSQ scores. No differences were seen in the communication scores of men versus women. Faculty rated US graduates significantly higher than international medical graduates. CONCLUSION: Our study provides evidence for the reliability and validity of the KEECC-A as a measure of physician communication skills. The KEECC-A appears to be a psychometrically sound, user-friendly communication tool, linked to an expert consensus statement, that can be quickly and accurately completed by multiple raters across diverse specialties. PMID- 21975615 TI - An institutional approach to assist program directors and coordinators with meeting the challenges of graduate medical education. AB - OBJECTIVE: To investigate whether a multimethod approach, including a new position dedicated to graduate medical education (GME) educator, online education modules, and program file audits, was associated with quality improvement in our residency programs. METHOD: Data related to GME audits, residency review committee citations and cycle lengths were entered into a database. We conducted statistical analyses and calculated effect sizes to explore whether these resources were associated with program quality, as measured by maintaining necessary program policies and files, implementation of multiple assessments, increased residency review committee cycle lengths, and reductions in the number of citations. RESULTS: The statistical analyses support the implementation of the GME educator, file audits, and online courses designed to improve the quality of residency education. CONCLUSIONS: The GME office will continue to conduct audits, develop online learning resources, and provide one-on-one communication between the GME educator and program coordinators and directors. Our approach could serve as a model for other institutions interested in enhancing institutional oversight and the quality of their programs. PMID- 21975616 TI - Educating Physicians-in-Training About Resource Utilization and Their Own Outcomes of Care in the Inpatient Setting. AB - BACKGROUND: Despite significant policy concerns about the role of inpatient resource utilization on rising medical costs, little information is provided to residents regarding their practice patterns and the effect on resource use. Improved knowledge about their practice patterns and costs might reduce resource utilization and better prepare physicians for today's health care market. METHODS: We surveyed residents in the internal medicine residency at the Hospital of the University of Pennsylvania. Based on needs identified via the survey, discussions with experts, and a literature review, a curriculum was created to help increase residents' knowledge about benchmarking their own practice patterns and using objective performance measures in the health care market. RESULTS: The response rate to our survey was 67%. Only 37% of residents reported receiving any feedback on their utilization of resources, and only 20% reported receiving feedback regularly. Even fewer (16%) developed, with their attending physician, a concrete improvement plan for resource use. A feedback program was developed that included automatic review of the electronic medical record to provide trainee specific feedback on resource utilization and outcomes of care including number of laboratory tests per patient day, laboratory cost per patient day, computed tomography scan ordering rate, length of stay, and 14-day readmission rate. Results were benchmarked against those of peers on the same service. Objective feedback was provided biweekly by the attending physician, who also created an action plan with the residents. In addition, an integrated didactic curriculum was provided to all trainees on the hospitalist service on a biweekly basis. CONCLUSIONS: Interns and residents do not routinely receive feedback on their resource utilization or ways to improve efficiency. A method for providing objective data on individual resource utilization in combination with a structured curriculum can be implemented to help improve resident knowledge and practice. Ongoing work will test the impact on resource utilization and outcomes. PMID- 21975617 TI - A reliable billing method for internal medicine resident clinics: financial implications for an academic medical center. AB - BACKGROUND: The financial success of academic medical centers depends largely on appropriate billing for resident-patient encounters. Objectives of this study were to develop an instrument for billing in internal medicine resident clinics, to compare billing practices among junior versus senior residents, and to estimate financial losses from inappropriate resident billing. METHODS: For this analysis, we randomly selected 100 patient visit notes from a resident outpatient practice. Three coding specialists used an instrument structured on Medicare billing standards to determine appropriate codes, and interrater reliability was assessed. Billing codes were converted to US dollars based on the national Medicare reimbursement list. Inappropriate billing, based on comparisons with coding specialists, was then determined for residents across years of training. RESULTS: Interrater reliability of Current Procedural Terminology components was excellent, with kappa ranging from 0.76 for examination to 0.94 for diagnosis. Of the encounters in the study, 55% were underbilled by an average of $45.26 per encounter, and 18% were overbilled by an average of $51.29 per encounter. The percentages of appropriately coded notes were 16.1% for postgraduate year (PGY) 1, 26.8% for PGY-2, and 39.3% for PGY-3 residents (P < .05). Underbilling was 74.2% for PGY-1, 48.8% for PGY-2, and 42.9% for PGY-3 residents (P < .01). There was significantly less overbilling among PGY-1 residents compared with PGY-2 and PGY-3 residents (9.7% versus 24.4% and 17.9%, respectively; P < .05). CONCLUSIONS: Our study reports a reliable method for assessing billing in internal medicine resident clinics. It exposed large financial losses, which were attributable to junior residents more than senior residents. The findings highlight the need for educational interventions to improve resident coding and billing. PMID- 21975618 TI - An assessment of an educational intervention on resident physician attitudes, knowledge, and skills related to adverse event reporting. AB - OBJECTIVE: Reporting and learning from events linked to patient harm and unsafe conditions is critical to improving patient safety. Programs that engage resident physicians in adverse event reporting can enhance patient safety and simultaneously address all 6 Accreditation Council for Graduate Medical Education competencies. Yet fewer than 60% of physicians know how to report adverse events and near misses, and fewer than 40% know what to report. Our study evaluated the effect of an educational intervention on anesthesiology residents' attitudes, knowledge, and skills related to adverse event reporting and the associated follow-up. METHODS: In a prospective study, anesthesiology residents participated in a training program focused on the importance of reporting methods and on reporting adverse events for patient safety. Quarterly adverse event reports were analyzed retrospectively for 2 years before the intervention and prospectively for 7 quarters after the intervention. Residents also completed a survey, before and 1 year after the intervention, that evaluated their attitudes, experience, and knowledge regarding adverse event reporting. RESULTS: After the intervention, the number of adverse event reports increased from 0 per quarter to almost 30 per quarter. We identified several categories of harm events, near misses, and unsafe conditions, including reports of disruptive providers. Of the harm events associated with invasive procedures, more than half were associated with lack of attending physician supervision. We also observed significant progress in the residents' ability to appropriately file a report, improved attitudes regarding the value of reporting and available emotional support, and a reduction in the perceived impediments to reporting. CONCLUSIONS: An educational intervention increased the number of adverse event reports submitted by anesthesiology residents, improved their attitudes about the importance of reporting, and produced a source for learning opportunities and process improvements in the delivery of anesthesia care. PMID- 21975619 TI - Defining the roles of advisors and mentors in postgraduate medical education: faculty perceptions, roles, responsibilities, and resource needs. AB - BACKGROUND: Residency program directors rely on an informal network of faculty mentors to provide guidance for residents. Faced with increasingly sophisticated competency-based evaluation systems and scrutiny of patient safety and resident well-being in today's environment, residency programs need more structured mechanisms for mentoring. OBJECTIVE: To clarify the role of resident advisors and mentors so that residents receive the right combination of direction and oversight to ensure their successful transition to the next phase of their careers. METHODS: The Duke Internal Medicine Residency Program undertook a formal assessment of the roles, responsibilities, and resource needs of its key faculty through a focus group made up of key faculty. A follow-up focus group of residents and chief residents was held to validate the results of the faculty group assessment. RESULTS: The distinction between advising and mentoring was our important discovery and is supported by literature that identifies that mentors and advisors differ in multiple ways. A mentor is often selected to match resources and expertise with a resident's needs or professional interests. An advisor is assigned with a role to counsel and guide the resident through the residency processes, procedures, and key learning milestones. CONCLUSION: The difference between the role of advisor and that of mentor is of critical importance and allowed for the evolution of faculty participants' role as resident advisors, including the formulation of expectations for advisors, and the creation of an advisor toolkit. Our modifiable toolkit can enhance the advising process for residents in many disciplines. We saw an improvement in resident satisfaction from 2006 to 2009. PMID- 21975620 TI - Who's My Doctor? First-Year Residents and Patient Care: Hospitalized Patients' Perception of Their "Main Physician". AB - BACKGROUND: Studies have shown that a large portion of patient satisfaction is related to physician care, especially when the patient can identify the role of the physician on the team. Because patients encounter multiple physicians in teaching hospitals, it is often difficult to determine who the patient feels is his or her main caregiver. Surveys evaluating resident physicians would help to improve patient satisfaction but are not currently implemented at most medical institutions. INTERVENTION: We created a survey to judge patient satisfaction and to determine who patients believe is their "main physician" on the teaching service. METHODS: Patients on a medical teaching service at The Miriam Hospital during 20 days in March 2008 were asked to complete the survey. A physician involved in the research project administered the surveys. Surveys included 3 questions that judged patient's perception and identification of their primary physician and 7 questions regarding patient satisfaction. Completed surveys were analyzed using averages. RESULTS: Of the 126 patients identified for participation, 102 (81%) completed the survey. Most patients identified the intern (first-year resident) as their main physician. Overall, more than 90% of patients expressed satisfaction with their main physician. CONCLUSION: Most patients on the teaching service perceived the intern as their main physician and were satisfied with their physician's care. One likely reason is that interns spend the greatest amount of time with patients on the teaching service. PMID- 21975621 TI - Mentoring for subspecialty training program directors: an unrecognized, unmet need? AB - BACKGROUND: The benefits of mentoring residents have been studied, but there is no research about mentoring new program directors. Program directors' responsibilities have become increasingly complicated, and they may not be adequately prepared for their role at the time of appointment without the benefit of mentoring that is specific to their new role. OBJECTIVE: To assess whether nephrology subspecialty program directors were specifically mentored and whether they felt prepared for the educational and administrative aspects of this role. METHODS: We conducted an electronic needs assessment survey of the nephrology subspecialty program directors through the American Society of Nephrology listserv for program directors. RESULTS: The survey response rate was 42% (58 of 139). Of the respondents, 58% did not feel adequately prepared when they first became subspecialty program directors, and only 32% reported having formal or informal mentoring for the role. Individuals who had served as associate program directors (34%) were more likely to report mentoring than those who had not (P = .02). Eighty percent of respondents reported that mentoring from another nephrology program director would have been beneficial during their first several years. CONCLUSIONS: This appears to be the first study specifically evaluating mentoring experiences relevant to the role of nephrology program director. As a result of this survey, the American Society of Nephrology Training Program Director Executive Committee recognized the need to provide opportunities for mentoring new nephrology program directors and formed a New Training Program Director Training and Mentoring Work Group to recommend initiatives for mentoring and training new program directors. Further investigation is needed to assess whether mentoring benefits subspecialty program directors and whether these findings can be generalized to other specialties and subspecialties. PMID- 21975622 TI - Utilization and barriers to mental health services among depressed medical interns: a prospective multisite study. AB - BACKGROUND: Compared with graduate students and young adults in the general population, depression is more prevalent among training physicians, yet physicians are often reluctant to seek mental health treatment. The purpose of this study is to identify perceived barriers to mental health treatment among depressed training physicians. METHODS: Subjects for this study were drawn from intern classes during the 2007-2008 and 2008-2009 academic years from 6 and 13 participating community and university hospitals, respectively. At 3-month intervals throughout the intern year, participants completed the Patient Health Questionnaire regarding current depressive symptoms and questions regarding current mental health treatment. We explored potential barriers to mental health treatment at the end of the intern year and determined the proportion of subjects screening positive for depression and seeking treatment through analysis of subject responses. Stepwise binary logistic regression was conducted to compare baseline characteristics among depressed interns who sought mental health treatment and those that did not. RESULTS: Of the 42.5% (278 of 654) of interns who screened positive for depression, 22.7% (63 of 278) reported receiving treatment during the intern year. The most frequently cited barriers to seeking treatment were time (91.5%), preference to manage problems on their own (75.1%), lack of convenient access (61.8%), and concerns about confidentiality (57.3%). Interns who had previously sought treatment for depression were more likely to seek treatment during internship. CONCLUSIONS: Despite high rates of depression, few interns appear to seek mental health treatment due to time constraints, lack of convenient access, concerns about confidentiality, and a preference to manage problems on their own. By identifying barriers to mental health treatment we can begin to remove obstacles to the delivery of evidence-based treatments and implement prevention, screening, and early detection programs to improve the mental health of physicians in training. PMID- 21975623 TI - Improving quality and patient satisfaction in a pediatric resident continuity clinic through advanced access scheduling. AB - OBJECTIVE: To evaluate the impact of advanced access scheduling in a pediatric residency clinic on resident and patient satisfaction, medical education, practice quality, and efficiency. METHODS: Residents were assigned to either the advanced access template (10 appointments available to patients and 2 physician overbooks) or the prior template (5 available and 8 overbooks). Outcomes included resident and patient satisfaction, appointment availability, and continuity of care and clinic costs. RESULTS: Patient satisfaction improved in 7 areas (P < .001). Residents in either template did not report an impact on medical education experiences. Significant increases were realized with appointment availability and the number of patients seen. Continuity also increased as the overflow/acute visits decreased (P < .001). Overall costs per visit decreased 22%. Because of the significant improvements in access, continuity, and efficiency, all residents were switched to the advanced access template after completion of the study. CONCLUSIONS: Improvement in access to the primary physician has a significant impact on patient satisfaction with health care delivery. This model optimizes the limited time that residents have in continuity clinic, and it has implications for health care delivery quality improvement. PMID- 21975624 TI - Quality Education and Safe Systems Training (QuESST): Development and Assessment of a Comprehensive Cross-Disciplinary Resident Quality and Patient Safety Curriculum. AB - BACKGROUND: Over the past decade, regulatory bodies have heightened their emphasis on health care quality and safety. Education of physicians is a priority in this effort, with the Accreditation Council for Graduate Medical Education requiring that trainees attain competence in practice-based learning and improvement and systems-based practice. To date, several studies about the use of resident education related to quality and safety have been published, but no comprehensive interdisciplinary curricula seem to exist. Effective, formal, comprehensive cross-disciplinary resident training in quality and patient safety appear to be a vital need. METHODS: To address the need for comprehensive resident training in quality and patient safety, we developed and assessed a formal standardized cross-disciplinary curriculum entitled Quality Education and Safe Systems Training (QuESST). The curriculum was offered to first-year residents in a large urban medical center. Preintervention and postintervention assessments and participant perception surveys evaluated the effectiveness and educational value of QuESST. RESULTS: A total of 138 first-year medical and pharmacy residents participated in the QuESST course. Paired analysis of preintervention and postintervention assessments showed significant improvement in participants' knowledge of quality and patient safety. Participants' perceptions about the value of the curriculum were favorable, as evidenced by a mean response of 1.8 on a scale of 1 (strongly agree) to 5 (strongly disagree) that the course should be taught to subsequent residency classes. CONCLUSION: QuESST is an effective comprehensive quality curriculum for residents. Based on these findings, our institution has made QuESST mandatory for all future first year resident cohorts. Other institutions should explore the value of QuESST or a similar curriculum for enhancing resident competence in quality and patient safety. PMID- 21975625 TI - Factors impacting hand hygiene compliance among new interns: findings from a mandatory patient safety course. AB - BACKGROUND: Residency is a critical transition during which individuals acquire lifelong behaviors important for professionalism and optimal patient care. One behavior is proper hand hygiene (HH), yet poor compliance with accepted HH practices remains a critical issue in many settings. This study explored the factors affecting hand hygiene compliance (HHC) in a diverse group of interns at the beginning of graduate training. METHODS: During a required patient safety course, we observed HH behaviors using a standardized patient encounter. Interns were instructed to perform a focused exam in a simulated inpatient environment with HH products available and clearly visible. Participants were blinded to the HH component of the study. An auditory alert was triggered if participants failed to perform prepatient encounter HH. Compliance rates and the number of alerts were recorded. All encounters were videotaped. RESULTS: The HHC among the 169 participants was 37.9% pre-encounter and was higher among female interns than males, although this difference was not statistically significant (41.6% versus 31.5%, P = .176). International medical graduates had significantly lower HHC compared with US graduates (23.2% versus 45.1%, P = .006). Most initially noncompliant participants performed HH after 1 alert (87.6%). DISCUSSION: The initial low rate of HHC in our sample is comparable to other studies. Using direct video surveillance and auditory alarms, we improved our success rates for prepatient encounter HHC. Our study identified medical school origin as an important factor for HHC, and the significantly lower compliance for international medical graduates compared with US graduates has not been previously reported. These findings should be considered in designing interventions such as intern orientation and clinical education programs to improve HH behaviors. PMID- 21975626 TI - A pilot study assessing knowledge of clinical signs and physical examination skills in incoming medicine residents. AB - BACKGROUND: Physical exam skills of medical trainees are declining, but most residencies do not offer systematic clinical skills teaching or assessment. OBJECTIVE: To assess knowledge of clinical signs and physical exam performance among incoming internal medicine residents. METHOD: For this study, 45 incoming residents completed a multiple choice question test to assess knowledge of clinical signs. A random selection of 20 underwent a faculty-observed objective structured clinical examination (OSCE) using patients with abnormal physical findings. Mean percentage scores were computed for the multiple choice question test, overall OSCE, and the 5 individual OSCE systems. RESULTS: The mean scores were 58.4% (14.6 of 25; SD 11. 5) for the multiple choice question test and 54.7% (31.7 of 58; SD 11.0) for the overall OSCE. Mean OSCE scores by system were cardiovascular 30.0%, pulmonary 69.2%, abdominal 61.6%, neurologic 67.0%, and musculoskeletal 41.7%. Analysis of variance showed a difference in OSCE system scores (P < .001) with cardiovascular and musculoskeletal scores significantly lower than other systems. CONCLUSION: Overall, physical exam knowledge and performance of new residents were unsatisfactory. There appears to be a pressing need for additional clinical skills training during medical school and residency training and we are planning a new clinical skills curriculum to address this deficiency. PMID- 21975627 TI - Night float teaching and learning: perceptions of residents and faculty. AB - BACKGROUND: Most internal medicine residency programs use a night float system to comply with resident duty hour limits. Night float assignments often comprise 7 to 10 weeks of scheduled clinical time during training. Despite this substantial allotment of time to night float, few studies have assessed the adequacy of learning opportunities during these rotations. We designed an exploratory study to assess resident and faculty views about the educational aspects of a typical internal medicine night float system. METHODS: Wright State University Boonshoft School of Medicine internal medicine residents and attending faculty were asked to complete a 25-item voluntary, anonymous survey. A 5-point Likert scale was used to assess perceptions of education during day and night rotations. RESULTS: The response rate was 52% (85 of 164). Residents rated teaching and learning on day rotations more positively than on night rotations for 17 of 25 (68%) items. Regarding night float, residents rated 14 of 25 items below 3.00; only one item was rated below 3.00 ("...H & P skills observed by attending") for day rotations. Attending physicians rated day rotations more highly for all 25 survey items. Faculty rated 13 of 25 items below 3.00 for night float and they rated no items below 3.00 for day rotations. Resident and faculty ratings differed significantly for 10 items, with 5 items receiving higher ratings by residents and 5 being rated more positively by faculty. CONCLUSION: Despite a substantial allotment of time to night rotations, there appear to be lost teaching and learning opportunities in the current night float system. Modification of the existing format may improve its educational value. PMID- 21975628 TI - Resident evaluation and remediation: a comprehensive approach. AB - BACKGROUND: A comprehensive evaluation and remediation program is an essential component of any residency program. The evaluation system should identify problems accurately and early and allow residents with problems to be assigned to a remediation program that effectively deals with them. Elements of a proactive remediation program include a process for outlining deficiencies, providing resources for improvement, communicating clear goals for acceptable performance, and reevaluating performance against these goals. INTERVENTION: In recognition of the importance of early detection and prompt remediation of the struggling resident, we sought to develop a multifaceted approach to resident evaluation with the aim of early identification and prompt remediation of difficulties. This article describes our comprehensive evaluation program and remediation program, which uses resources within our radiology department and institutional graduate medical education office. DISCUSSION: An effective evaluation system should identify problems accurately and early, whereas a proactive remediation program should effectively deal with issues once they are identified. PMID- 21975629 TI - Subtest scores from the in-training examination: an evaluation tool for an obstetric-anesthesia rotation. AB - OBJECTIVE: To evaluate resident performance in the obstetric-anesthesia rotation using resident portfolios and their In-Training Examination scores, which are provided by the American Board of Anesthesiology/American Society of Anesthesiologists. METHODS: We reviewed academic portfolios for second- and third year anesthesiology residents at a single institution from 2006-2008 to examine United States Medical Licensing Exam Step 1 and 2 scores, grade for obstetrics gynecology in medical school, and performance on the In-Training Examination. Faculty evaluation of medical knowledge and correlations for the various scores were obtained. RESULTS: We examined scores for 43 residents. The subtest score for obstetric anesthesia increased after completing a rotation in obstetric anesthesia, 26.1 +/- 10.3 versus 36.3 +/- 10.6 (P = .02). The subtest score correlated with United States Medical Licensing Exam Step 2, r = 0.46 (P = .027) but not with United States Medical Licensing Exam Step 1 or with the grade obtained in medical school. There was no correlation between faculty evaluations of medical knowledge and resident subtest scores in obstetric anesthesia. CONCLUSIONS: Subtest scores in obstetric anesthesia are valid and provide a tool for the assessment of the educational program of a rotation. Knowledge as assessed by a faculty member is different from the knowledge assessed on a written examination. Both methods can help provide a more complete assessment of the resident and the rotation. PMID- 21975630 TI - Teaching systems-based competency in anesthesiology residency: development of an education and assessment tool. AB - BACKGROUND: The Accreditation Council for Graduate Medical Education requires programs to educate and evaluate residents in 6 competencies, including systems based practice. We designed a survey and assessment tool to address the competency as it pertains to anesthetic drug costs in an academic center. METHODS: Residents, certified registered nurse anesthetists, and faculty were asked to complete an anesthetic drug-cost survey without relying on reference materials. After a combination of compulsory in-class didactic sessions and web based education, the participants were asked to design an anesthetic, give example cases, and determine costs. The initial task was repeated 1 year later. RESULTS: Our preintervention survey revealed that most practitioners knew very little about anesthetic drug costs, regardless of level of training or degree. All residents completed the mandatory online education tool, more than 80% attended the departmental grand rounds program, and 100% met the goal of designing an anesthetic for all cases within the preset price limit. A repeat of the cost estimate produced an improvement in cost estimates with reduction in variability (P < .05, Student unpaired t test), although estimates of volatile anesthetic and reversal agent costs did not achieve significance at the .05 level for any of the 3 cases. CONCLUSION: Introducing a formalized teaching and assessment tool has improved our residents' understanding of anesthetic drug costs, and improved our ability to teach and assess the systems-based practice competency. PMID- 21975632 TI - Multisource feedback in the ambulatory setting. AB - BACKGROUND: The Accreditation Council for Graduate Medical Education has mandated multisource feedback (MSF) in the ambulatory setting for internal medicine residents. Few published reports demonstrate actual MSF results for a residency class, and fewer still include clinical quality measures and knowledge-based testing performance in the data set. METHODS: Residents participating in a year long group practice experience called the "long-block" received MSF that included self, peer, staff, attending physician, and patient evaluations, as well as concomitant clinical quality data and knowledge-based testing scores. Residents were given a rank for each data point compared with peers in the class, and these data were reviewed with the chief resident and program director over the course of the long-block. RESULTS: Multisource feedback identified residents who performed well on most measures compared with their peers (10%), residents who performed poorly on most measures compared with their peers (10%), and residents who performed well on some measures and poorly on others (80%). Each high-, intermediate-, and low-performing resident had a least one aspect of the MSF that was significantly lower than the other, and this served as the basis of formative feedback during the long-block. CONCLUSION: Use of multi-source feedback in the ambulatory setting can identify high-, intermediate-, and low-performing residents and suggest specific formative feedback for each. More research needs to be done on the effect of such feedback, as well as the relationships between each of the components in the MSF data set. PMID- 21975631 TI - Preparation, confidence, and attitudes about chronic noncancer pain in graduate medical education. AB - BACKGROUND: Physicians report they feel ill-prepared to manage chronic noncancer pain (CNCP), in part because of inadequate training. Published studies and clinical observation demonstrate that trainees lack confidence and reflect negative attitudes about CNCP. Overall, there is minimal published guidance on specific specialty roles and responsibilities in CNCP management. OBJECTIVE: The purpose of this study was to assess resident preparation, confidence, and attitudes about CNCP across graduate medical education programs and to assess resident perception of roles and responsibilities in CNCP management. METHODS: In 2006 we surveyed residents from 13 graduate medical education programs in 3 institutions about CNCP and report quantitative and qualitative analyses of survey responses from 246 respondents. RESULTS: A total of 59% of respondents rated their medical school preparation and 36% rated their residency preparation as "fair" or "poor"; only 17% reported being "confident" or "very confident" in assessing patients with CNCP; and 30% used negative or derogatory terms (eg, manipulative, irritable, needy) to describe patients with CNCP. Respondents from postgraduate years 3-6 were more than twice as likely as postgraduate year 1 or postgraduate year 2 respondents (44% versus 21% and 20%, respectively) to use negative or derogatory terms (P = .0007). Respondents were significantly more likely to report that pain specialists are "good" or "excellent" in managing CNCP compared with generalists (73% versus 6%; P < .0001). CONCLUSION: Education in pain management should begin in medical school and continue through graduate medical education, regardless of specialty. Early and sustained training interventions are needed to foster empathy in caring for patients with pain. Residency and fellowhip training should impart a clear understanding of each specialty's role and responsibilities in pain management to better foster patient centered pain care. PMID- 21975633 TI - Enhancing competency in professionalism: targeting resident advance directive education. AB - BACKGROUND: Education about advance directives typically is incorporated into medical school curricula and is not commonly offered in residency. Residents' experiences with advance directives are generally random, nonstandardized, and difficult to assess. In 2008, an advance directive curriculum was developed by the Scott & White/Texas A&M University System Health Science Center College of Medicine (S&W/Texas A&M) internal medicine residency program and the hospital's legal department. A pilot study examining residents' attitudes and experiences regarding advance directives was carried out at 2 medical schools. METHODS: In 2009, 59 internal medicine and family medicine residents (postgraduate year 2-3 [PGY-2, 3]) completed questionnaires at S&W/Texas A&M (n = 32) and The University of Texas Medical School at Houston (n = 27) during a validation study of knowledge about advance directives. The questionnaire contained Likert response items assessing attitudes and practices surrounding advance directives. Our analysis included descriptive statistics and analysis of variance (ANOVA) to compare responses across categories. RESULTS: While 53% of residents agreed/strongly agreed they had "sufficient knowledge of advance directives, given my years of training," 47% disagreed/strongly disagreed with that statement. Most (93%) agreed/strongly agreed that "didactic sessions on advance directives should be offered by my hospital, residency program, or medical school." A test of responses across residency years with ANOVA showed a significant difference between ratings by PGY-2 and PGY-3 residents on 3 items: "Advance directives should only be discussed with patients over 60," "I have sufficient knowledge of advance directives, given my years of training," and "I believe my experience with advance directives is adequate for the situations I routinely encounter." CONCLUSION: Our study highlighted the continuing need for advance directive resident curricula. Medical school curricula alone do not appear to be sufficient for residents' needs in this area. PMID- 21975634 TI - Smoking cessation in family medicine: effects of an area health education center training program. AB - BACKGROUND AND OBJECTIVES: Many clinicians have not received adequate training in smoking cessation. We examined the effects of a tobacco training program on clinician behavior, attitudes, knowledge, and comfort related to smoking cessation. METHODS: In a prospective cohort study, family medicine residents and faculty completed a pretest, followed by an educational intervention that encompassed presentations on smoking cessation resources, motivational interviewing, and the neurobiology of addiction and pharmacotherapy. After 3 months, participants completed a postintervention survey. Results were analyzed using chi-square tests to examine the effects of training. RESULTS: Thirty-three residents and faculty completed the pretraining survey and 25 completed the posttraining survey. Following training, participants were more familiar and comfortable with Public Health Service Clinical Practice Guidelines (P < .0001). No significant differences were found in performance of the 5 As (Ask, Advise, Assess, Assist, and Arrange) or other behaviors, including providing assistance with counseling, cessation plans, resources, or pharmacotherapy. There were no improvements in knowledge of specific intervention plans or attitudes related to identifying and counseling smokers. CONCLUSION: A multidisciplinary tobacco training program increases clinician familiarity and comfort with practice guidelines, and may contribute to improving care activities that promote a healthy lifestyle. Future research should explore other interventions that have the potential of changing practice patterns on a larger scale. Future studies should also assess the effect of training programs on patient-oriented outcomes. PMID- 21975635 TI - Revisiting Social Network Utilization by Physicians-in-Training. AB - OBJECTIVE: To measure and compare the frequency and content of online social networking among 2 cohorts of medical students and residents (2007 and 2009). METHODS: Using the online social networking application Facebook, we evaluated social networking profiles for 2 cohorts of medical students (n = 528) and residents (n = 712) at the University of Florida in Gainesville. Objective measures included existence of a profile, whether it was made private, and whether any personally identifiable information was included. Subjective outcomes included photographic content, affiliated social groups, and personal information not generally disclosed in a doctor-patient encounter. We compared our results to our previously published and reported data from 2007. RESULTS: Social networking continues to be common amongst physicians-in-training, with 39.8% of residents and 69.5% of medical students maintaining Facebook accounts. Residents' participation significantly increased (P < .01) when compared to the 2007 data. Individuals in the 2009 cohort had significantly more "friends" (P < .01), belonged to more "groups" (P < .01), and were more likely to limit public access to their profiles through the use of privacy settings (P < .01) than the individuals in the 2007 cohort. DISCUSSION: Online social networking application use by physicians-in-training remains common. While most now limit access to their profiles, personal profiles that still allow public access exhibited a few instances of unprofessional behavior. Concerns remain related to the discovery of content in violation of patient privacy and the expansive and impersonal networks of online "friends" who may view profiles. PMID- 21975636 TI - Addressing the primary care deficit: building primary care leaders for tomorrow. PMID- 21975637 TI - Should Medical Grades be Standardized? Improving the Resident Selection Process. PMID- 21975638 TI - Experiential leadership training for pediatric chief residents: impact on individuals and organizations. AB - BACKGROUND: The past decade has seen a proliferation of leadership training programs for physicians that teach skills outside the graduate medical education curriculum. OBJECTIVE: To determine the perceived value and impact of an experiential leadership training program for pediatric chief residents on the chief residents and on their programs and institutions. METHODS: The authors conducted a retrospective study. Surveys were sent to chief residents who completed the Chief Resident Training Program (CRTP) between 1988 and 2003 and to their program directors and department chairs asking about the value of the program, its impact on leadership capabilities, as well as the effect of chief resident training on programs and institutions. RESULTS: Ninety-four percent of the chief residents and 94% of program directors and department chairs reported that the CRTP was "very" or "somewhat" relevant, and 92% of the chief residents indicated CRTP had a positive impact on their year as chief resident; and 75% responded it had a positive impact beyond residency. Areas of greatest positive impact included awareness of personality characteristics, ability to manage conflict, giving and receiving feedback, and relationships with others. Fifty-six percent of chief residents reported having held a formal leadership position since chief residency, yet only 28% reported having received additional leadership training. CONCLUSION: The study demonstrates a perceived positive impact on CRTP participants and their programs and institutions in the short and long term. PMID- 21975639 TI - Institutional attributes associated with innovation and improvement: results of a multisite study. AB - BACKGROUND: To date, no studies have explored why some teaching hospitals and health systems appear to offer a more fertile environment for innovation and improvement in the learning environment. As a consequence, little is known about the role of organizational attributes and culture in fostering innovation and improvements in settings where residents learn and participate in care, though these have been studied extensively in the general literature on organizations. AIMS: The goals of our study entailed (1) gathering ground-level observations on processes and common attributes; (2) disseminating this information for adoption and adaptation; and (3) exploring whether the current accreditation model may present barriers to institution- and program-level innovation. METHODS: We conducted a qualitative study of 4 institutions, successful in innovation and improvement in their learning environment, and sought to replicate the findings with a second group of 5 institutions. RESULTS: THREE THEMES EMERGED FROM THE INTERVIEWS AND SITE VISITS OF THE PARTICIPANTS IN THE ALPHA PHASE: (1) a structure and culture that promote integration and inclusion; (2) a recognition of the value of resident education to the institution; and (3) a learning organization rooted in the extensive use of data and ongoing change, improvement, and innovation. CONCLUSIONS: Some of the concepts identified in our small sample of "innovative" institutions could be relatively easily adopted or adapted by others that seek to enhance innovation and improvement in the learning environment. In contrast, the structural factors that characterized 3 of the 4 alpha participants, particularly the organization and compensation of faculty, may not be generalizable to many other institutions. PMID- 21975640 TI - Defining neurocognitive disorders. PMID- 21975641 TI - Environmental influences on physical activity in rural adults: the relative contributions of home, church and work settings. AB - BACKGROUND: This study examines the relative contribution of social (eg, social support) and physical (eg, programs and facilities) aspects of worksite, church, and home settings to physical activity levels among adults in rural communities. METHODS: Data are from a cross-sectional survey of 268 African American and Caucasian adults, ages 40-70, living in southwest Georgia. Separate regression models were developed for walking, moderate, vigorous, and total physical activity as measured in METs-minutes-per-week. RESULTS: Social support for physical activity was modest in all 3 settings (mean scores 1.5-1.9 on a 4-point scale). Participants reported limited (<1) programs and facilities for physical activity at their worksites and churches. An interaction of physical and social aspects of the home setting was observed for vigorous and moderate physical activity and total METs. There were also interactions between gender and social support at church for vigorous activity among women, and between race and the physical environment at church for moderate physical activity. A cross-over interaction was found between home and church settings for vigorous physical activity. Social support at church was associated with walking and total METs. CONCLUSIONS: Homes and churches may be important behavioral settings for physical activity among adults in rural communities. PMID- 21975643 TI - The algebra of the general Markov model on phylogenetic trees and networks. AB - It is known that the Kimura 3ST model of sequence evolution on phylogenetic trees can be extended quite naturally to arbitrary split systems. However, this extension relies heavily on mathematical peculiarities of the associated Hadamard transformation, and providing an analogous augmentation of the general Markov model has thus far been elusive. In this paper, we rectify this shortcoming by showing how to extend the general Markov model on trees to include incompatible edges; and even further to more general network models. This is achieved by exploring the algebra of the generators of the continuous-time Markov chain together with the "splitting" operator that generates the branching process on phylogenetic trees. For simplicity, we proceed by discussing the two state case and then show that our results are easily extended to more states with little complication. Intriguingly, upon restriction of the two state general Markov model to the parameter space of the binary symmetric model, our extension is indistinguishable from the Hadamard approach only on trees; as soon as any incompatible splits are introduced the two approaches give rise to differing probability distributions with disparate structure. Through exploration of a simple example, we give an argument that our extension to more general networks has desirable properties that the previous approaches do not share. In particular, our construction allows for convergent evolution of previously divergent lineages; a property that is of significant interest for biological applications. PMID- 21975644 TI - A multiscale hybrid model for pro-angiogenic calcium signals in a vascular endothelial cell. AB - Cytosolic calcium machinery is one of the principal signaling mechanisms by which endothelial cells (ECs) respond to external stimuli during several biological processes, including vascular progression in both physiological and pathological conditions. Low concentrations of angiogenic factors (such as VEGF) activate in fact complex pathways involving, among others, second messengers arachidonic acid (AA) and nitric oxide (NO), which in turn control the activity of plasma membrane calcium channels. The subsequent increase in the intracellular level of the ion regulates fundamental biophysical properties of ECs (such as elasticity, intrinsic motility, and chemical strength), enhancing their migratory capacity. Previously, a number of continuous models have represented cytosolic calcium dynamics, while EC migration in angiogenesis has been separately approached with discrete, lattice-based techniques. These two components are here integrated and interfaced to provide a multiscale and hybrid Cellular Potts Model (CPM), where the phenomenology of a motile EC is realistically mediated by its calcium dependent subcellular events. The model, based on a realistic 3-D cell morphology with a nuclear and a cytosolic region, is set with known biochemical and electrophysiological data. In particular, the resulting simulations are able to reproduce and describe the polarization process, typical of stimulated vascular cells, in various experimental conditions. Moreover, by analyzing the mutual interactions between multilevel biochemical and biomechanical aspects, our study investigates ways to inhibit cell migration: such strategies have in fact the potential to result in pharmacological interventions useful to disrupt malignant vascular progression. PMID- 21975645 TI - New insights into ion regulation of cephalopod molluscs: a role of epidermal ionocytes in acid-base regulation during embryogenesis. AB - The constraints of an active life in a pelagic habitat led to numerous convergent morphological and physiological adaptations that enable cephalopod molluscs and teleost fishes to compete for similar resources. Here, we show for the first time that such convergent developments are also found in the ontogenetic progression of ion regulatory tissues; as in teleost fish, epidermal ionocytes scattered on skin and yolk sac of cephalopod embryos appear to be responsible for ionic and acid-base regulation before gill epithelia become functional. Ion and acid-base regulation is crucial in cephalopod embryos, as they are surrounded by a hypercapnic egg fluid with a Pco(2) between 0.2 and 0.4 kPa. Epidermal ionocytes were characterized via immunohistochemistry, in situ hybridization, and vital dye staining techniques. We found one group of cells that is recognized by concavalin A and MitoTracker, which also expresses Na(+)/H(+) exchangers (NHE3) and Na(+) K(+)-ATPase. Similar to findings obtained in teleosts, these NHE3-rich cells take up sodium in exchange for protons, illustrating the energetic superiority of NHE based proton excretion in marine systems. In vivo electrophysiological techniques demonstrated that acid equivalents are secreted by the yolk and skin integument. Intriguingly, epidermal ionocytes of cephalopod embryos are ciliated as demonstrated by scanning electron microscopy, suggesting a dual function of epithelial cells in water convection and ion regulation. These findings add significant knowledge to our mechanistic understanding of hypercapnia tolerance in marine organisms, as it demonstrates that marine taxa, which were identified as powerful acid-base regulators during hypercapnic challenges, already exhibit strong acid-base regulatory abilities during embryogenesis. PMID- 21975646 TI - Functional characterization and localization of a gill-specific claudin isoform in Atlantic salmon. AB - Claudins are the major determinants of paracellular epithelial permeability in multicellular organisms. In Atlantic salmon (Salmo salar L.), we previously found that mRNA expression of the abundant gill-specific claudin 30 decreases during seawater (SW) acclimation, suggesting that this claudin is associated with remodeling of the epithelium during salinity change. This study investigated localization, protein expression, and function of claudin 30. Confocal microscopy showed that claudin 30 protein was located at cell-cell interfaces in the gill filament in SW- and fresh water (FW)-acclimated salmon, with the same distribution, overall, as the tight junction protein ZO-1. Claudin 30 was located at the apical tight junction interface and in cell membranes deeper in the epithelia. Colocalization with the alpha-subunit of the Na(+)-K(+)-ATPase was negligible, suggesting limited association with mitochondria-rich cells. Immunoblotting of gill samples showed lower claudin 30 protein expression in SW than FW fish. Retroviral transduction of claudin 30 into Madin-Darby canine kidney cells resulted in a decreased conductance of 19%. The decreased conductance correlated with a decreased permeability of the cell monolayer to monovalent cations, whereas permeability to chloride was unaffected. Confocal microscopy revealed that claudin 30 was expressed in the lateral membrane, as well as in tight junctions of Madin-Darby canine kidney cells, thereby paralleling the findings in the native gill. This study suggests that claudin 30 functions as a cation barrier between pavement cells in the gill and also has a general role in cell-cell adhesion in deeper layers of the epithelium. PMID- 21975647 TI - Glucagon-like peptide-1 receptor agonists suppress water intake independent of effects on food intake. AB - Glucagon-like peptide-1 (GLP-1) is produced by and released from the small intestine following ingestion of nutrients. GLP-1 receptor (GLP-1R) agonists applied peripherally or centrally decrease food intake and increase glucose stimulated insulin secretion. These effects make the GLP-1 system an attractive target for the treatment of type 2 diabetes mellitus and obesity. In addition to these more frequently studied effects of GLP-1R stimulation, previous reports indicate that GLP-1R agonists suppress water intake. The present experiments were designed to provide greater temporal resolution and site specificity for the effect of GLP-1 and the long-acting GLP-1R agonists, exendin-4 and liraglutide, on unstimulated water intake when food was and was not available. All three GLP 1R ligands suppressed water intake after peripheral intraperitoneal administration, both in the presence of and the absence of food; however, the magnitude and time frame of water intake suppression varied by drug. GLP-1 had an immediate, but transient, hypodipsic effect when administered peripherally, whereas the water intake suppression by IP exendin-4 and liraglutide was much more persistent. Additionally, intracerebroventricular administration of GLP-1R agonists suppressed water intake when food was absent, but the suppression of intake showed modest differences depending on whether the drug was administered to the lateral or fourth ventricle. To the best of our knowledge, this is the first demonstration of GLP-1 receptor agonists affecting unstimulated, overnight intake in the absence of food, the first test for antidipsogenic effects of hindbrain application of GLP-1 receptor agonists, and the first test of a central effect (forebrain or hindbrain) of liraglutide on water intake. Overall, these results show that GLP-1R agonists have a hypodipsic effect that is independent of GLP-1R-mediated effects on food intake, and this occurs, in part, through central nervous system GLP-1R activation. PMID- 21975648 TI - Rapid post-oral stimulation of intake and flavor conditioning by glucose and fat in the mouse. AB - Although widely assumed to have only satiating actions, nutrients in the gut can also condition increases in intake in some cases. Here we studied the time course of post-oral nutrient stimulation of ingestion in food-restricted C57BL/6J mice. In experiment 1, mice adapted to drink a 0.8% sucralose solution 1 h/day, rapidly increased their rate of licking (within 4-6 min) when first tested with an 8% glucose solution and even more so in tests 2 and 3. Other mice decreased their licking rate when switched from sucralose to 8% fructose, a sugar that is sweet like glucose but lacks positive post-oral effects in mice. The glucose-stimulated drinking is due to the sugar's post-oral rather than taste properties, because sucralose is highly preferred to glucose and fructose in brief choice tests. A second experiment showed that the glucose-stimulated ingestion is associated with a conditioned flavor preference in both intact and capsaicin-treated mice. This indicates that the post-oral stimulatory action of glucose is not mediated by capsaicin-sensitive visceral afferents. In experiment 3, mice consumed flavored saccharin solutions as they self-infused water or glucose via an intragastric (IG) catheter. The glucose self-infusion stimulated ingestion within 13-15 min in test 1 and produced a conditioned increase in licking that was apparent in the initial minute of tests 2 and 3. Experiment 4 revealed that IG self-infusions of a fat emulsion also resulted in post-oral stimulation of licking in test 1 and conditioned increases in tests 2 and 3. These findings indicate that glucose and fat can generate stimulatory post-oral signals early in a feeding session that increase ongoing ingestion and condition increases in flavor acceptance and preference revealed in subsequent feeding sessions. The test procedures developed here can be used to investigate the peripheral and central processes involved in stimulation of intake by post-oral nutrients. PMID- 21975649 TI - Adenosine A1-receptor deficiency diminishes afferent arteriolar and blood pressure responses during nitric oxide inhibition and angiotensin II treatment. AB - Adenosine mediates tubuloglomerular feedback responses via activation of A(1) receptors on the renal afferent arteriole. Increased preglomerular reactivity, due to reduced nitric oxide (NO) production or increased levels of ANG II and reactive oxygen species (ROS), has been linked to hypertension. Using A(1) receptor knockout (A(1)(-/-)) and wild-type (A(1)(+/+)) mice we investigated the hypothesis that A(1)-receptors modulate arteriolar and blood pressure responses during NO synthase (NOS) inhibition or ANG II treatment. Blood pressure and renal afferent arteriolar responses were measured in nontreated mice and in mice with prolonged N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME) or ANG II treatment. The hypertensive responses to L-NAME and ANG II were clearly attenuated in A(1)(-/-) mice. Arteriolar contractions to L-NAME (10(-4) mol/l; 15 min) and cumulative ANG II application (10(-12) to 10(-6) mol/l) were lower in A(1)(-/-) mice. Simultaneous treatment with tempol (10(-4) mol/l; 15 min) attenuated arteriolar responses in A(1)(+/+) but not in A(1)(-/-) mice, suggesting differences in ROS formation. Chronic treatment with L-NAME or ANG II did not alter arteriolar responses in A(1)(-/-) mice, but enhanced maximal contractions in A(1)(+/+) mice. In addition, chronic treatments were associated with higher plasma levels of dimethylarginines (asymmetrical and symmetrical) and oxidative stress marker malondialdehyde in A(1)(+/+) mice, and gene expression analysis showed reduced upregulation of NOS-isoforms and greater upregulation of NADPH oxidases. In conclusion, adenosine A(1)-receptors enhance preglomerular responses during NO inhibition and ANG II treatment. Interruption of A(1) receptor signaling blunts l-NAME and ANG II-induced hypertension and oxidative stress and is linked to reduced responsiveness of afferent arterioles. PMID- 21975650 TI - Male lineages in the Himalayan foothills: a commentary on Y-chromosome haplogroup diversity in the sub-Himalayan Terai and Duars populations of East India. PMID- 21975651 TI - Mass migration on a polymer surface caused by photoinduced molecular rotation. AB - We demonstrated the formation of a photoinduced surface relief grating using thin films comprising a photochromic molecular motor, 9-(2-phenyl-2,3-dihydro cyclopenta[a]naphthalen-1-ylidene)-9H-fluorene. Results show that mass migration occurred by patterned light irradiation prepared from interfered laser beams and a photomask. PMID- 21975652 TI - Ti-STT: a new zeotype shape selective oxidation catalyst. AB - A new zeotype titanium silicate oxidation catalyst with the STT topology has been synthesized from direct synthesis. Ti-STT has a microporous structure with small pore openings, allowing shape selective oxidation catalysis. The isomorphous substitution of Si by Ti in the framework has been confirmed by Raman, FT-IR, UV VIS and XANES spectroscopies. PMID- 21975653 TI - From evidence-based medicine to guidelines and recommendations: a long and winding road. PMID- 21975654 TI - Risks of being an anaesthesiologist. PMID- 21975656 TI - Useful sign to diagnose tinea capitis-'ear sign'. PMID- 21975655 TI - Mosaic trisomy 9 presenting with congenital heart disease, facial dysmorphism and pigmentary skin lesions: intricate issues of genetic counseling. AB - Chromosomal mosaicism for full aneuploidy involving chromosome 9 is an uncommon chromosomal abnormality. Mosaic trisomy 9 clinical manifestations are highly variable and difficult to predict. The authors present a case of mosaic trisomy 9 with typical clinical manifestations(facial dysmorphism, various internal organ malformations and severe psychomotor retardation), pigmentary mosaic skin lesions along the lines of Blaschko and evidence of maternal uniparental disomy in skin. PMID- 21975657 TI - Universal acquired melanosis in siblings. AB - Generalized pigmentation in a child may be seen in a variety of disorders which can be clinically differentiated. Accuracy of diagnosis can be increased by classifications based on both clinical and histological findings. The authors report a case of siblings in whom hyperpigmentation started at age of about 6 mo and was progressing. Histology of skin revealed shortening and blunting of rete ridges with presence of melanocytes in stratum basal layer. This is a rare type of hypermelanosis and termed as universal acquired melanosis or carbon baby syndrome. This is a rare presentation and first case report in siblings. PMID- 21975660 TI - Using implicit associations towards fruit consumption to understand fruit consumption behaviour and habit strength relationships. AB - An implicit association test (IAT) was used to investigate how habit strength, implicit attitudes and fruit consumption interrelate. Fifty-two participants completed a computerized IAT and provided measures of fruit consumption and related habit strength. Implicit attitudes moderated the habit strength-fruit consumption relationship; stronger relationships were observed when implicit attitudes were more positive. Amongst those with strong fruit habits, more positive associations with fruit were found for those who had recently consumed sufficient fruits compared to those who had not. Findings demonstrate the relevance of implicit positive associations in understanding the relationship between fruit consumption habits and subsequent fruit consumption. PMID- 21975659 TI - Long bone fracture detection in suspected child abuse: contribution of lateral views. AB - BACKGROUND: ACR guidelines for routine skeletal survey for child abuse recommend only AP radiographs of the long bones; however, many institutions add lateral radiographs. OBJECTIVES: To evaluate whether adding lateral radiographs for long bones changes the frequency and confidence of fracture detection in skeletal survey radiographs for suspected abuse. MATERIALS AND METHODS: We identified 100 children younger than 2 years of age who underwent skeletal survey for child abuse; 56 with multiple long bone fractures, 22 with a single fracture and 22 with no fractures. Four radiologists (two pediatric radiologists, one pediatric radiology fellow and one general radiologist) evaluated two randomized series (one series included only frontal, and the other series, frontal and lateral radiographs). Likert scale of 1-5 was used to score for detection of metaphyseal and diaphyseal fractures. RESULTS: For combined readers, significantly more metaphyseal fractures (P = 0.01) were detected with the two-views series of radiographs compared with the frontal-only view; there was no significant difference for diaphyseal fractures. Confidence was also significantly higher for the two-views series. Kappa improved (from 0.32 to 0.48) when the lateral view was added only for the metaphyseal fractures. CONCLUSION: Adding lateral radiographs resulted in increased detection and confidence levels of metaphyseal fractures. PMID- 21975661 TI - Type D personality is associated with maladaptive health-related behaviours. AB - Type D personality (the combination of negative affect and social inhibition) is associated with poor prognosis in cardiac patients. The current study aims to investigate the relationship between Type D and health-related behaviours. In a cross-sectional study, 200 healthy participants completed measures of Type D personality, and health-related behaviours. The results showed that Type D individuals engaged in more unhealthy behaviours including smoking, poor diet and lack of physical activity than non-Type D individuals. The association between Type D personality and maladaptive health behaviours may represent one mechanism to explain the link between Type D and ill-health. PMID- 21975662 TI - Parents' anxieties about the risk of HIV/AIDS for their Deaf and hard of hearing adolescents in South Africa: a qualitative study. AB - Adolescents who are Deaf or hard of hearing may be vulnerable to HIV/AIDS. Adolescents' open communication with parents encourages positive sexuality. The relationship between the Deaf adolescent and their parent could be obstructed by communication difficulties. This article explores parents' anxieties about HIV risk. We interviewed nine parents of Deaf adolescents in South Africa. We explored their fears of the risk of HIV/AIDS for their children. Participants believed that their children were at risk of HIV infection. Although they did communicate with their children about sexuality and HIV/AIDS, some experienced communication difficulties. Communicative relationships between these adolescents and their parents should be encouraged. PMID- 21975663 TI - Impact of metal on the DNA photocleavage activity and cytotoxicity of ferrocenyl terpyridine 3d metal complexes. AB - Ferrocenyl terpyridine 3d metal complexes and their analogues, viz. [M(Fc tpy)(2)](ClO(4))(2) (1-4), [Zn(Ph-tpy)(2)](ClO(4))(2) (5) and [Zn(Fc-dpa)(2)]X(2) (X = ClO(4), 6; PF(6), 6a), where M = Fe(II) in 1, Co(II) in 2, Cu(II) in 3 and Zn(II) in 4, Fc-tpy is 4'-ferrocenyl-2,2':6',2''-terpyridine, Ph-tpy is 4'-phenyl 2,2':6',2''-terpyridine and Fc-dpa is ferrocenyl-N,N-dipicolylmethanamine, are prepared and their DNA binding and photocleavage activity in visible light studied. Complexes 2, 4, 5 and 6a that are structurally characterized by X-ray crystallography show distorted octahedral geometry with the terpyridyl ligands binding to the metal in a meridional fashion, with Fc-dpa in 6a showing a facial binding mode. The Fc-tpy complexes display a charge transfer band in the visible region. The ferrocenyl (Fc) complexes show a quasi-reversible Fc(+)-Fc redox couple within 0.48 to 0.66 V vs. SCE in DMF-0.1 M TBAP. The DNA binding constants of the complexes are ~10(4) M(-1). Thermal denaturation and viscometric data suggest DNA surface binding through electrostatic interaction by the positively charged complexes. Barring the Cu(II) complex 3, the complexes do not show any chemical nuclease activity in the presence of glutathione. Complexes 1-4 exhibit significant plasmid DNA photocleavage activity in visible light via a photoredox pathway. Complex 5, without the Fc moiety, does not show any DNA photocleavage activity. The Zn(II) complex 4 shows a significant PDT effect in HeLa cancer cells giving an IC(50) value of 7.5 MUM in visible light, while being less toxic in the dark (IC(50) = 49 MUM). PMID- 21975665 TI - Congenital thoracic arterial anomalies in adults: a CT overview. AB - Congenital thoracic arterial anomalies can be incidentally detected in adults from imaging studies performed for other indications. Multidetector computed tomography plays a critical role in the noninvasive assessment of these anomalies and associated cardiac, mediastinal, or parencyhmal changes by providing volumetric data. Radiologists should be familiar with imaging findings of these anomalies to avoid misinterpretation and to establish accurate diagnosis. In this article, we review the imaging characteristics of congenital aortic, pulmonary, and aortopulmonary anomalies with an emphasis on multidetector computed tomography findings. We illustrate the CT findings of congenital arterial anomalies such as double aortic arch, right aortic arch, aortic coarctation, pseudocoarctation, interrupted aortic arch, interruption (absence) of the pulmonary artery, pulmonary artery sling, pulmonary artery stenosis, transposition of great vessels, truncus arteriosus, aortopulmonary window, and patent ductus arteriosus. PMID- 21975664 TI - Pediatricians' awareness of diagnostic medical radiation effects and doses: are the latest efforts paying off? AB - PURPOSE: The number of radiological exams performed on children increases each year. We assessed the current understanding of radiation doses and risks among a sample group of pediatricians and evaluated whether the latest efforts to improve radiation awareness affected the results. MATERIALS AND METHODS: A multiple choice survey comprising 16 questions was answered by 237 pediatricians in 10 hospitals. RESULTS: Although the overall knowledge was poor, underestimation of radiation doses of common radiological procedures was significantly lower (75.2%) than that reported in previous surveys (87%-97%). In contrast to previous reports, the percentage of underestimates did not increase for computed tomography (74.8%), and residents scored (7.5+/-5.1) better than specialists (11.0+/-6.3) in estimating the radiation doses (P < 0.001). Only 3.1% of the pediatricians had received formal education on medical radiation, and 89% were not aware of the ALARA (As Low As Reasonably Achievable) principle. CONCLUSION: Pediatricians' radiation dose awareness is better than it was a few years ago, and the latest educational efforts in the form of campaigns, reports, publications, and news media seem to have had a beneficial effect. The younger generation had better knowledge, possibly because they were exposed to discussions of radiation dosage at an earlier stage in their training. PMID- 21975666 TI - Gray-scale and color Doppler US findings of amniotic sheets. AB - PURPOSE: To identify the gray-scale and color Doppler ultrasonography (US) findings of amniotic sheets. MATERIALS AND METHODS: Among 1201 pregnant patients who underwent detailed second trimester US, nine had amniotic sheets. An amniotic sheet was defined as a shelf-like structure in the uterine cavity with a free edge not attached to the fetus or umbilical cord. There was no major fetal anomaly observed in any patient. Eight patients had solitary amniotic sheets, and one patient had double sheets. All gray-scale and Doppler US features of amniotic sheets were noted. RESULTS: The incidence of an amniotic sheet was determined to be 0.75% (ten amniotic sheets were observed in nine patients). On gray-scale US images, amniotic sheets were observed as bands of tissue that originated from the uterine wall with a triangular-shaped base that tapered toward the free edge. A three-layered appearance was identified in seven amniotic sheets. Using Doppler US images, four of ten sheets showed a low-resistance arterial flow, and five of ten sheets showed non-pulsatile venous flows. No vascularization was observed in one patient with a thin, membranous sheet. CONCLUSION: Gray-scale US is sufficient for the diagnosis of amniotic sheets because of the typical US characteristics; however, Doppler US findings of amniotic sheets are highly variable. Thus, Doppler US may not be beneficial in the diagnosis of amniotic sheets. PMID- 21975668 TI - Growth hormone to improve short bowel syndrome intestinal autonomy: a pediatric randomized open-label clinical trial. AB - BACKGROUND: The ability of growth hormone (GH) to promote the weaning-off of parenteral nutrition (PN) in short bowel syndrome (SBS) is unclear. No randomized controlled study is available in children. This study was undertaken to determine if GH could enhance the weaning off of PN in PN-dependent children with SBS. METHODS: A prospective randomized open-label multicenter study was performed in 14 patients (mean age, 9 +/- 1.4 years) with SBS (average small bowel length, 33 cm) and long-term PN dependency (8 years) on an unrestricted diet. A standardized PN decrease with and without GH (0.14 mg/kg/d) was conducted. The patients were randomized to either a GH group (4 months of GH) or a control (CTR) group (4 months without GH, followed by 4 months with GH). Blood tests and a nutrition assessment of enteral and parenteral intakes were performed. Groups were compared with the Wilcoxon test. RESULTS: Treatment with GH did not improve the weaning off of PN (decrease in PN caloric intake of 32.5% +/- 9.6% in the GH group vs 35.2% +/- 8.7% in the CTR group, nonsignificant). In the CTR group, GH treatment induced an additional but not statistically significant decrease of 8.8% +/- 12.4% in daily calories. Parenteral needs returned to near basal rates 6 months after GH discontinuation (GH: 77.6% +/- 10.6% vs CTR: 73.2% +/- 7.4%). Weight decreased slightly in both groups. No biological parameters varied significantly. CONCLUSIONS: GH did not improve the weaning off of PN in PN-dependent children with SBS. PMID- 21975672 TI - Developing epidemiologic studies of people's lived experience: the Swiss Spinal Cord Injury Cohort Study as a case in point. PMID- 21975670 TI - Central venous catheter thrombosis associated with 70% ethanol locks in pediatric intestinal failure patients on home parenteral nutrition: a case series. AB - Central venous catheter (CVC) ethanol locks may reduce catheter-related bloodstream infection (CRBSI). Four children with intestinal failure on home parenteral nutrition (HPN) were selected for 70% ethanol locks because of their high rate of CRBSI. The 70% ethanol locks were instilled at a volume equal to the estimated internal volume of the CVC. Two children (aged 4 and 11 years) received 70% ethanol locks as CRBSI prophylaxis; another 2 children (aged 10 and 11 years) received 70% ethanol locks as adjunctive treatment for CRBSI. All 4 children developed either visible thrombosis in the CVC or CVC occlusion. To the authors' knowledge, this is the first report of CVC thrombosis associated with ethanol lock therapy in the pediatric HPN population. Although none of the CVCs were removed due to occlusion, these events raise serious concerns about the use of high-concentration ethanol locks. PMID- 21975669 TI - Nutrition in burns: Galveston contributions. AB - Aggressive nutrition support is recommended following severe burn injury. Initially, such injury results in a prolonged and persistent hypermetabolic response mediated by a 10- to 20-fold elevation in plasma catecholamines, cortisol, and inflammatory mediators. This response leads to twice-normal metabolic rates, whole-body catabolism, muscle wasting, and severe cachexia. Thus, it is relevant to review the literature on nutrition in burns to adjust/update treatment. Failure to meet the increased substrate requirements may result in impaired wound healing, multiorgan dysfunction, increased susceptibility to infection, and death. Therefore, aggressive nutrition support is essential to ensure adequate burn care, attenuate the hypermetabolic response, optimize wound healing, minimize devastating catabolism, and reduce morbidity and mortality. Here, the authors provide nutrition recommendations gained from prospective trials, retrospective analyses, and expert opinions based on the authors' practices in Galveston, Texas, and Vienna, Austria. PMID- 21975673 TI - Setting up a cohort study on functioning: deciding what to measure. AB - The objectives of this article were to (1) answer the question of what to measure in a cohort study in which the main focus is the understanding of functioning over time for a specific population and to (2) describe the process of determining what to measure using a theory-informed selection of domains of functioning based on the International Classification of Functioning, Disability and Health (ICF). The Swiss Spinal Cord Injury Cohort Study, a cohort study being carried out in Switzerland for a population of persons with spinal cord injury, was used as an example. A set of domains for the Swiss Spinal Cord Injury Cohort Study was identified demonstrating the application of the methodology. This set consisted of 45 categories of the ICF. Defining what to measure using the ICF is a valuable technique for the cohort researcher because it guarantees comparability of data and comprehensiveness of scope, enhancing the prospects of the study results being understood and is consequently used by health professionals as well as in other contexts, such as in health and social policy. PMID- 21975674 TI - How to measure what matters: development and application of guiding principles to select measurement instruments in an epidemiologic study on functioning. AB - The purpose of this article was to describe and to apply a comprehensive set of guiding principles in the selection of measurement instruments for a longitudinal epidemiologic study focusing on functioning using the International Classification of Functioning, Disability, and Health (ICF) as reference framework. Based on the literature, the ICF linkage rules, and the definition of ICF categories to be measured, the following guiding principles for selecting measurement instruments are defined: redundancy, efficiency, level of detail of information, comparability, feasibility, and truth and discrimination. Examples illustrate that the application of guiding principles allows for a systematic and reasoned process of measurement instrument selection and thus offers a potential solution for the multifaceted challenges that one encounters in the selection of measurement instruments. It is transparently demonstrated how the ICF linkage rules enable researchers to address issues such as efficiency, comparability, and redundancy and how the definition of a set of ICF categories to be measured allows assessing inefficiencies in measurement instruments. Because of the ICF linkage rules and the definition of ICF categories to be measured, new guiding principles for selecting measurement instruments emerge. The main challenges lie in the difficulty to quantify and prioritize the applicability of guiding principles and the fact that they strongly interact. Notably, the prioritization and application of guiding principles must be defined considering the specific characteristics and aims of the specific study. PMID- 21975675 TI - Category specification and measurement instruments in large spinal cord injury studies: a comparison using the International Classification of Functioning, Disability, and Health as a reference. AB - The objective of this paper was to examine whether large longitudinal studies have comprehensively covered the functioning of persons with spinal cord injuries (SCI), using the International Classification of Functioning, Disability and Health (ICF) as reference framework. First, the literature was reviewed to select relevant studies. Second, category specifications measured in the included studies were linked to the ICF and compared with the Brief ICF Core Sets for postacute and chronic situations. Finally, all measurement instruments used to assess these category specifications were listed according to the corresponding ICF category. Four studies were included: the National SCI Database in the United States, the Australian SCI Register, the European Multicenter Study about SCI, and the Dutch research program "Restoration of mobility in SCI rehabilitation." All measures could be linked to the ICF Core Sets. However, all studies only partly covered (range, 14-27) the 49 categories of the Brief ICF Core Sets. Least well covered were categories of body structures and environmental factors. Besides the International Standards for Neurological Classification of SCI (American Spinal Injury Association Impairment Scale), the areas of functioning were measured using the same measurement instruments in all studies. None of the included longitudinal studies comprehensively cover functioning. There is the need to develop truly comprehensive longitudinal studies in SCI. PMID- 21975676 TI - Design of the Swiss Spinal Cord Injury Cohort Study. AB - The overall goal of the Swiss Spinal Cord Injury Cohort Study (SwiSCI) is to gain a better understanding of how to support functioning, health maintenance, and quality-of-life of persons with spinal cord injury (SCI) along the continuum of care, in the community, and along their life span. The purpose of this study was to present the SwiSCI study design. SwiSCI is composed of three complementary pathways and will include Swiss persons 16 yrs or older who have diagnoses of traumatic or nontraumatic SCI. Pathway 1 is a retrospective study of medical files of patients admitted to one of the collaborating SCI centers between 2005 and 2009. Pathway 2 is a nationwide survey of persons with chronic SCI. Pathway 3 is an inception cohort study including persons with newly acquired SCI. SwiSCI is conducted in collaboration with the Swiss Paraplegic Association and the major specialized rehabilitation centers in Switzerland. Measurement instruments that are to be used in Pathway 2 and 3 cover body structures and functions, activities, participation, life satisfaction, and personal and environmental factors. SwiSCI is a prospective cohort study that will contribute to a comprehensive understanding of the lived experience of persons with SCI. PMID- 21975677 TI - Measuring body structures and body functions from the International Classification of Functioning, Disability, and Health perspective: considerations for biomedical parameters in spinal cord injury research. AB - OBJECTIVE: The aims of this study were to provide a selection of biomedical domains based on the comprehensive International Classification of Functioning, Disability, and Health (ICF) core sets for spinal cord injury (SCI) and to present an overview of the corresponding measurement instruments. DESIGN: Based on the Biomedical Domain Set, the SCI literature, the International Spinal Cord Society international data sets, and the Spinal Cord Injury Rehabilitation Evidence project publications were used to derive category specifications for use in SCI research. Expert opinion was used to derive a priority selection. The same sources were used to determine candidate measurement instruments for the specification of body functions and body structures using an example, and guiding principles were applied to select the most appropriate biomedical measurement instrument(s) for use in an SCI research project. RESULTS: Literature searches were performed for 41 second-level ICF body functions categories and for four second-level ICF body structures categories. For some of these categories, only a few candidate measurement instruments were found with limited variation in the type of measurement instruments. CONCLUSIONS: An ICF-based measurement set for biomedical aspects of functioning with SCI was established. For some categories of the ICF core sets for SCI, there is a need to develop measurement instruments. PMID- 21975678 TI - Domain sets and measurement instruments on participation and environmental factors in spinal cord injury research. AB - The understanding and measurement of participation and environmental context in spinal cord injury (SCI) is critically important. However, there is limited understanding of the environment-participation relationship in SCI research. There is little consensus on what is and on how to measure participation and its environmental determinants in the SCI. The objective of this article is to develop a set of International Classification of Functioning, Disability and Health (ICF)-based SCI Participation and Environment Domain Set and measurement instruments that intend to measure those domains. ICF categories from the ICF components of activities and participation and environmental factors based on the comprehensive ICF Core Set for SCI and the ICF Core Set for vocational rehabilitation were merged. Measurement instruments were selected based on published systematic reviews of measurement instruments in SCI. There were 128 ICF categories or domains in total (38 for environmental factors and 90 for activities and participation). There were six measurement instruments on environmental factors and six for participation based on existing systematic reviews. This article presents a domain set that is relevant to conducting research on the social and environmental perspectives, in an effort to understand and measure functioning in SCI (i.e., "SCI participation domain set" and "SCI environment domain set," respectively). The sample of SCI Participation and Environment Measurement Instruments gathered indicate the comprehensiveness and depth of the different domains. Guiding principles on the utilization of these measurement instruments depending on the purpose and design of a research study are highly recommended to investigators. PMID- 21975679 TI - Capturing the psychologic-personal perspective in spinal cord injury. AB - OBJECTIVE: The overall objective of this study was to illustrate a systematic approach for capturing the psychologic-personal perspective in International Classification of Functioning, Disability and Health-based comprehensive research on spinal cord injury (SCI) in terms of what and how to measure. The specific aims were to identify (1) relevant areas of research for capturing the psychologic-personal factors in a study that is planned and conceptualized according to the comprehensive context of the International Classification of Functioning, Disability and Health, using SCI as a case in point; (2) a set of domains relevant for SCI research from a psychologic-personal perspective; and (3) suitable measurement instruments that can be considered for the assessment of those identified domains based on a set of predefined guiding principles. DESIGN: The psychologic-personal factor structure was developed based on an item pool of 1246 entries from secondary analyses of available data from SCI studies. The domain set for psychologic-personal factors was identified through reviewing the scientific literature in PubMed and PsycInfo. The set of measurement instruments was collected using available measurement reviews, searches in the literature, instrument databases, and further sources and was selected using guiding principles. RESULTS: Forty specific psychologic-personal factors, subdivided into seven areas of research, were identified: (1) sociodemographic personal characteristics, (2) the position in the immediate social and physical context, (3) personal history and biography, (4) feelings, (5) thoughts and beliefs, (6) motives, and (7) patterns of experience and behavior. The psychologic-personal factors domain set contains both cross-cutting outcome domains, namely quality-of life, life satisfaction, subjective well-being, and sociodemographic personal characteristics, life events, positive and negative affect, perceived stress, locus of control, self-efficacy, purpose in life, coping, lifestyle, and personality. For each of the identified domains, a pool of measurement instruments was listed, and the application of predefined guiding principles for measurement instrument selection was exemplified for self-efficacy. It resulted in the selection of the General Self-Efficacy Scale by Schwarzer and Jerusalem (Measures in Health Psychology: A User's Portfolio. Causal and Control Beliefs. pp. 35-37; 1995). CONCLUSIONS: The results of the current article contributed to creating a transparent protocol for the Swiss Spinal Cord Injury Cohort study, coordinated by the Swiss Paraplegic Research in Nottwil, Switzerland. This article also stresses the relevance of the comprehensive approach to SCI and the consideration of the psychologic-personal perspective in this approach. The study, therefore, hopes to encourage scientists to use the International Classification of Functioning, Disability and Health and the psychologic-personal perspective as a frame of reference for their research. Furthermore, the research reported in this article can inform the World Health Organization's future development of the personal factors classification in the International Classification of Functioning, Disability and Health. PMID- 21975680 TI - Investigation of beta-catenin and E-cadherin expression in Dukes B2 stage colorectal cancer with tissue microarray method. Is it a marker of metastatic potential in rectal cancer? AB - beta-catenin and E cadherin are both membrane-associated proteins which are essential regulators and providers of cellular adhesion. In the metastatic cascade of malignant tumours, detachment of tumour cells from each other is a very important step. It has been shown in several tumour types, that reduced expression of these proteins is important. The aim of our study was to clarify the expression profile of these proteins, and correlate the findings with the metastasizing potential of early stage colon and rectal cancers. Formalin fixed and paraffin embedded samples from 79 Dukes B2 stage colorectal cancer were examined using a tissue microarray approach. The expression of beta-catenin and E cadherin proteins was determined immunohistochemically. Our findings indicated that there is a tendency for metastatic spread in cases when membranous expression of beta-catenin is lost (p = 0.062). Similarly metastases in negative cases developed more rapidly, than in positive ones (p = 0.05). Survival rate was worse in the negative cases. The risk of metastasis in rectal cancer was significantly higher in the beta-catenin membranously negative than positive groups (p = 0.024) and in case of beta-catenin nuclear expression the risk was also higher (p = 0.047). Reduced E-cadherin expression also correlated with development of metastatic disease, but this association was statistically not significant. The immunohistochemical analysis of 79 cases shows that in Dukes B2 stage colorectal tumours clarification of beta-catenin and E-cadherin expression patterns is reliable for predicting the metastatic potential of early stage rectal cancer and hence the method may have relevant implications in the therapeutic management of these cancers. PMID- 21975681 TI - Transparent reporting of studies relevant to physical therapy practice. AB - BACKGROUND: There was a clear grow, in the last 2 decades, of up to 6 fold in scientific articles that are directly relevant to physical therapy practice. However, along with this fast grow; little attention has been given to transparency when reporting research methods and results. More recently, groups of researchers around the world have made successful attempts to address this issue by creating guidelines that will help researchers not only on the preparation of manuscripts but also on making sure that important details related to design and methodology are controlled and reported. OBJECTIVE: To present four specific reporting guidelines, which are best known as "statements". DISCUSSION: A network named EQUATOR (Enhancing the Quality and Transparency of Health Research) was created with the main mission of providing basic principles for responsible and transparent reporting. The EQUATOR network encompasses, among others, the CONSORT statement which is related to randomized controlled trials; the PRISMA statement, which is related to systematic reviews and meta-analysis; the STROBE Statement, which is related to observational studies; and the STARD statement, which is related to reporting of accuracy of diagnostic tests. Some journals have recommended the use of these statements, while in others their use is mandatory. The goal of the use of these statements by journals is to guarantee fast decisions regarding publication and the best possible quality of reporting. Ultimately, it will help readers, including physical therapists, to make better decisions in clinical practice. PMID- 21975682 TI - High-voltage electrical stimulation improves nerve regeneration after sciatic crush injury. AB - BACKGROUND: Peripheral nerve injury causes prolonged functional limitation being a clinical challenge to identify resources that accelerates its recovery. OBJECTIVES: To investigate the effect of high-voltage electrical stimulation (HVES) on the morphometric and functional characteristics of the regenerated nerve after crush injury in rats. METHODS: Twenty Wistar rats were randomly allocated into 4 groups: Control (CON) - without injury and without HVES; Denervated (D) - sciatic nerve crush only; Denervated + HVES - sciatic nerve crush and HVES; SHAM - without injury but HVES. The HVES and SHAM groups were stimulated (100 Hz; minimum voltage of 100 V, 20 MUs, 100 MUs interpulse interval) for 30 min/day, 5 days/week. The sciatic functional index (SFI) was evaluated before the injury and at the 7th, 14th and 21st postoperatory (PO) days. Neural components and the area density of connective tissue, blood vessels and macrophages were analyzed. RESULTS: Axonal diameter was higher on the HVES than on D group, reaching almost 80% above the control values after 21 days (p<0.05). Fiber diameter and myelin sheath thickness were higher on the HVES than on D group (p<0.05) reaching 96.5% and 100% of the control values, respectively. Functional recovery at the 14th PO day was better on group HVES. The macrophages and connective tissue area density was lower on the HVES group, while blood vessels number did not differ among groups. CONCLUSIONS: The HVES accelerated the functional recovery, potentiated the nerve fibers maturation and decreased macrophages and connective tissue area density, suggesting acceleration of neural repair. PMID- 21975683 TI - Upper extremity joint stresses during walkerassisted ambulation in post-surgical patients. AB - BACKGROUND: A walker is a common device prescribed for ambulatory assistance for individuals with balance difficulties or to reduce lower extremity demands following injury or surgery. The long-term use of a walker imposes significant demands on the patient's upper extremities that may lead to increased risk for development of secondary conditions such as wrist, elbow or shoulder pain. OBJECTIVE: To describe the joint kinematics, forces and moments of the wrist, elbow and shoulder in a sample of twenty patients that were using a walker as a result of total joint surgery of the hips and knees. METHODS: Three-dimensional upper extremity kinematics were recorded using a motion capture system synchronized with forces and torques transmitted through a walker instrumented with force transducers in the handles. RESULTS: Compressive forces were found to be nearly 20% of the body weight at each of the upper extremity joints, both surgical and non-surgical sides, being the greatest force at the wrist and decreasing proximally. Compression forces were greater in the non-surgical side limb at the wrist and at the elbow. CONCLUSION: Our findings indicated that loads on upper extremity joints associated with the use of a walker for assisted ambulation are high and further studies are needed to address the cause-effect relationship between the actual joint loading and the development of secondary musculoskeletal upper extremity complaints in more frail patients. PMID- 21975684 TI - Babesia ovis as the main causative agent of sheep babesiosis in Iran. AB - Babesiosis is a haemoparasitic disease with high economical losses in livestock industry worldwide. The early diagnosis and successful therapy of babesiosis belong to the key steps of control and health management of livestock. Ethanol fixed blood samples of 400 sheep were analyzed for Babesia infection. Reverse line blot (RLB) was established specifically for Theileria lestoquardi, Theileria (China 1), Theileria (China 2), Theileria ovis, Theileria separata, Babesia ovis, Babesia motasi, Babesia crassa, and Babesia (Lintan). The DNA was extracted from the ethanol-fixed blood samples and amplified with a common primer pair derived from 18S rRNA gene, amplifying both Theileria spp. as well as Babesia spp. Regarding the differences in the length of nucleotide sequences of the polymerase chain reaction (PCR) products obtained from Theileria spp. and Babesia spp., the PCR products derived from Babesia spp. were out screened and analyzed by RLB. The RLB analysis showed that 28 samples within the 400 blood samples were B. ovis positive. No B. motasi, B. crassa, or Babesia (Lintan) could be detected. The sequence analysis of one PCR product as a representative for other B. ovis positive PCR products confirmed the results of RLB. Our results and the results of other investigators showed that B. ovis could be considered as a main causative agent of sheep babesiosis in Iran. Furthermore, our results also showed that RLB can be used as a reliable method for a simultaneous differentiation of Theileria and Babesia species from each other. PMID- 21975685 TI - Retraction note to: Conservative management of acute appendicitis. PMID- 21975686 TI - Multidisciplinary management of recurrent hepatocellular carcinoma following liver transplantation. AB - INTRODUCTION: Tumor recurrence remains a main limitation to the long-term survival of patients following liver transplantation for hepatocellular carcinoma (HCC). While the majority of patients recur in the first two years after transplantation, late recurrence is not infrequent. DISCUSSION: Most common sites of recurrence in order of decreasing frequency are liver graft, lung, bone, abdominal lymph nodes, adrenal glands and peritoneum. Reported five-year survival after surgical resection ranges from 27-88%. Few patients, however, are candidates for surgical resection. Other therapeutic options for recurrent HCC include systemic therapy, intra-arterial therapy, or radiation therapy. Although systemic molecular targeted therapy is generally tolerated with very few interactions with immunosuppressive medications, there is only modest success regarding prolongation of survival. Utilization of radiation therapy for extrahepatic recurrences similarly has minimal impact on overall survival, but may effectively in palliate symptoms. While late recurrence is associated with a more favorable prognosis than early recurrences, prognosis is still poor. CONCLUSION: Late recurrence of HCC following transplantation should be borne in mind even after many years from transplant. Surgical salvage, when feasible, remains a viable treatment option in select patients with a chance for long-term survival. A multi-disciplinary approach is critical as different therapeutic modalities have a role in treating recurrent HCC following transplant. PMID- 21975687 TI - Colorectal Infraperitoneal anastomosis: the effects of perioperative supplemental oxygen administration on the anastomotic dehiscence. AB - BACKGROUND: The role of supplemental oxygen therapy in the healing of colorectal anastomosis is still very much at an experimental stage. The aim of the present study, prospective randomized, was to assess the effect of administration of perioperative supplemental oxygen therapy on infraperitoneal anastomosis, where the risk of leakage is higher. METHODS: We enrolled 72 patients between February, 2008 and February, 2011, who underwent elective open infraperitoneal anastomosis for rectal cancer (middle and low). Patients were assigned randomly to an oxygen/air mixture with a fraction of inspired oxygen (FiO2) of 30% (n = 37) or 80% (n = 35). Administration was commenced after induction of anesthesia and maintained for 6 h after surgery. RESULTS: The overall anastomotic leak rate was 16.6% (12 out of 72); 8 patients (21.6%) had an anastomotic dehiscence in the 30% FiO2 group and 4 (11.4%) in the 80% FiO2 group (p < 0.05). The risk of anastomotic leak was 46% lower in the 80% FiO2 group (RR, 0.63; 95% confidence interval, 0.42-0.98) vs. the 30% FiO2. CONCLUSION: Therefore, supplemental 80% FiO2 during and for 6 h after major rectal cancer surgery, reducing postoperative anastomotic dehiscence, should be considered part of ongoing quality improvement activities related to surgical care, with few risks to the patient and little associated cost. PMID- 21975688 TI - Laser treatment for verrucous hemangioma. PMID- 21975689 TI - Association of hypertension with small, dense low-density lipoprotein in patients without metabolic syndrome. AB - A higher proportion of small, dense low-density lipoprotein (sdLDL) is known to be associated with a high prevalence of cardiovascular disease in association with metabolic syndrome (MS). Hypertension (HTN) is one of the known risk factors for MS. However, whether HTN is associated with sdLDL in patients without MS is not yet clear. The lipid profiles, including low-density-lipoprotein (LDL) subfractions, of 383 consecutive subjects were evaluated. The patients without MS consisted of 198 hypertensive patients (non-MS/HTN group) and 108 normotensive subjects (non-MS/non-HTN group). The peak and mean particle diameter of LDL were measured by gradient gel electrophoresis. Plasma total cholesterol, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride (TG), HDL cholesterol/Apo A1, LDL-C/ApoB and Apo(A1, B, CII and E) levels did not differ between the non-MS/non-HTN and non-MS/HTN groups. When analyzing LDL subfraction, the absolute amount of patterns A and B was not different between the non-MS/non HTN and non-MS/HTN groups. Compared with the non-MS/non-HTN groups, the proportion of sdLDL was higher in the non-MS/HTN group (37.7% versus 39.9%, P=0.046), but not significant after adjustment of waist circumference, serum TG, age and statin usage. The proportion of sdLDL to total LDL was higher in hypertensive subjects, even those without MS, than in normotensive subjects. However, this difference of LDL subfraction in hypertensive patients is associated with higher waist circumference, higher serum TG, older age and more statin usage. This result suggests that HTN may contribute to atherosclerosis and endothelial dysfunction with associated risk factors that influence LDL size. PMID- 21975690 TI - The relationship between aortic stiffness and changes in retinal microvessels among Asian ischemic stroke patients. AB - Large-artery stiffness is a risk factor for stroke, including cerebral small vessel disease. Retinal microvascular changes are thought to mirror those in cerebral microvessels. We investigated the relationship between aortic stiffness and retinal microvascular changes in Asian ischemic stroke patients. We studied 145 acute ischemic stroke patients in Singapore who had aortic stiffness measurements using carotid-femoral pulse wave velocity (cPWV). Retinal photographs were assessed for retinal microvessel caliber and qualitative signs of focal arteriolar narrowing, arteriovenous nicking and enhanced arteriolar light reflex. Aortic stiffening was associated with retinal arteriolar changes. Retinal arteriolar caliber decreased with increasing cPWV (r=-0.207, P=0.014). After adjusting for age, gender, hypertension, diabetes, mean arterial pressure and small-vessel stroke subtype, patients within the highest cPWV quartile were more likely to have generalized retinal arteriolar narrowing defined as lowest caliber tertile (odds ratio (OR) 6.84, 95% confidence interval (CI) 1.45-32.30), focal arteriolar narrowing (OR 13.85, CI 1.82-105.67), arteriovenous nicking (OR 5.08, CI 1.12-23.00) and enhanced arteriolar light reflex (OR 3.83, CI 0.89 16.48), compared with those within the lowest quartile. In ischemic stroke patients, aortic stiffening is associated with retinal arteriolar luminal narrowing as well as features of retinal arteriolosclerosis. PMID- 21975691 TI - Valve-based microfluidic compression platform: single axon injury and regrowth. AB - We describe a novel valve-based microfluidic axon injury micro-compression (AIM) platform that enables focal and graded compression of micron-scale segments of single central nervous system (CNS) axons. The device utilizes independently controlled "push-down" injury pads that descend upon pressure application and contact underlying axonal processes. Regulated compressed gas is input into the AIM system and pressure levels are modulated to specify the level of injury. Finite element modeling (FEM) is used to quantitatively characterize device performance and parameterize the extent of axonal injury by estimating the forces applied between the injury pad and glass substrate. In doing so, injuries are normalized across experiments to overcome small variations in device geometry. The AIM platform permits, for the first time, observation of axon deformation prior to, during, and immediately after focal mechanical injury. Single axons acutely compressed (~5 s) under varying compressive loads (0-250 kPa) were observed through phase time-lapse microscopy for up to 12 h post injury. Under mild injury conditions (< 55 kPa) ~73% of axons continued to grow, while at moderate (55-95 kPa) levels of injury, the number of growing axons dramatically reduced to 8%. At severe levels of injury (> 95 kPa), virtually all axons were instantaneously transected and nearly half (~46%) of these axons were able to regrow within the imaging period in the absence of exogenous stimulating factors. PMID- 21975692 TI - Donor-acceptor molecular figures-of-eight. AB - The intermolecular template-directed synthesis, separation and characterisation of two constitutional isomers that are self-complexing donor-acceptor [1]rotaxanes has been achieved by click chemistry, starting from a pi-electron deficient tetracationic cyclophane containing two azide functions and a pi electron rich 1,5-dioxynaphthalene-containing polyether chain terminated by propargyl groups. PMID- 21975693 TI - Coexpression of chaperonin GroEL/GroES markedly enhanced soluble and functional expression of recombinant human interferon-gamma in Escherichia coli. AB - Recombinant human interferon-gamma (rhIFN-gamma) is a protein of great potential for clinical therapy due to its multiple biological activities. However, overexpressing rhIFN-gamma in Escherichia coli was found to accumulate as cytoplasmic inclusion bodies. In this work, a system for soluble and active expression of rhIFN-gamma was constructed by coexpressing chaperonin GroEL/GroES in E. coli. The rhIFN-gamma gene was fused to a pET-28a expression vector, and rhIFN-gamma was partially expressed as the soluble form following coexpression with a second vector producing chaperonin GroEL/GroES. The fermentation of recombinant E. coli harboring rhIFN-gamma and GroEL/GroES plasmids was investigated, and the optimized conditions were as follows: culture temperature of 25 degrees C, incubation time of 8 h, isopropyl-beta-D-thio-galactoside concentration of 0.2 mM, and L-arabinose concentration of 0.5 g/L. As a result, the expression level of rhIFN-gamma was improved accordingly by 2.2-fold than the control, while a significantly positive correlation was also found between the ratio of supernatant to precipitate of rhIFN-gamma and the amount of chaperonin. Circular dichroism spectra, fluorescence spectra, size exclusion chromatography, and chemical crosslinking method were applied to characterize rhIFN-gamma, indicating that the three-dimensional structure of rhIFN-gamma was identical to that of the native rhIFN-gamma. The enzyme-linked immunosorbent assay for active rhIFN-gamma quantification showed that coexpression yielded 72.91 mg rhIFN-gamma per liter fermentation broth. Finally, protein-protein interactions between rhIFN gamma and chaperonin were analyzed using the yeast two-hybrid system, which provided the direct evidence that chaperonin GroEL/GroES interacted with rhIFN gamma to increase the soluble expression and presented the potential in producing efficiently recombinant proteins. PMID- 21975694 TI - Development of a novel probiotic delivery system based on microencapsulation with protectants. AB - The establishment of the health-promoting benefits of probiotics is challenged by the antimicrobial bio-barriers throughout the host's gastrointestinal (GI) tract after oral administration. Although microencapsulation has been frequently utilised to enhance the delivery of probiotics, microcapsules of sub-100 MUm were found to be ineffective and therefore questioned as an effective delivery vehicle for viable probiotics despite the sensory advantage. In this study, four probiotics strains were encapsulated in chitosan-coated alginate microcapsules of sub-100 MUm. Only a minor protective effect was observed from this original type of microcapsule. In order to enhance the survival of these probiotics, sucrose, a metabolisable sugar, and lecithin vesicles were added to the wall material. Both of the ingredients could be readily encapsulated with the probiotics, and protected them from stresses in the simulated GI fluids. The metabolisable sugar effectively increased the survival of the probiotics in gastric acid, mainly through energizing the membrane-bound F1F0-ATPases. The lecithin vesicles proved to alleviate the bile salt stress, and hence notably reduced the viability loss at the elevated bile salt concentrations. Overall, three out of the total four probiotics in the reinforced sub-100 MUm microencapsules could significantly survive through an 8-h sequential treatment of the simulated GI fluids, giving less than 1-log drop in viable count. The most vulnerable strain of bifidobacteria also yielded a viability increase of 3-logs from this protection. In conclusion, the sub-100 MUm microcapsules can be a useful vehicle for the delivery of probiotics, as long as suitable protectants are incorporated in the wall matrix. PMID- 21975695 TI - The early on-treatment perihepatic lymph node response predicts sustained viral response of anti-hepatitis C virus therapy. AB - BACKGROUND AND AIMS: In chronic hepatitis C, the change of perihepatic lymph nodal size after antiviral therapy could be a marker of virologic response. Whether the on-treatment nodal manifestations predict virologic responses is unknown. METHODS: Patients (n=88) with biopsy-proven chronic hepatitis C received standard doses of bi-therapy for 24 weeks; sequential changes of the perihepatic lymph nodes were evaluated prospectively by ultrasound. Pretreatment and on treatment factors were analyzed and correlated with sustained virologic response, focusing on early on-treatment nodal changes (12 weeks). RESULTS: Perihepatic lymph nodes were prevalent in 75% of the patients; 72 patients (81.8%) achieved sustained viral response. Before treatment, no factor was significantly associated with the nodal prevalence or size. The pretreatment nodal width (mean 5.3 vs. 3.6 mm; P=0.023) and the on-treatment nodal manifestations including a reduction in nodal width at 12 weeks of antiviral treatment (median; 1.05 vs. 0 mm, P=0.029) and a reduction of nodal volume at the end of treatment (24 weeks; median 0.62 vs. -0.01 ml, P=0.015) were significantly correlated with the sustained virologic response. A reduction of nodal width greater than 2.5 mm at 12 weeks always predicts sustained virologic response (100 vs. 77%; P=0.019). CONCLUSION: Results confirm the high prevalence of perihepatic lymphadenopathy in patients with chronic hepatitis C. The use of the nodal width measurement in routine ultrasound follow-up may be a simpler early predictor of sustained virologic response during standard bi-therapy. PMID- 21975696 TI - Fecal immunochemical test and small bowel lesions detected on capsule endoscopy: results of a prospective study in patients with obscure occult gastrointestinal bleeding. AB - BACKGROUND: Fecal immunochemical test (FIT) is gaining popularity as a screening tool for colorectal cancer. The introduction of capsule endoscopy (CE) enables an assessment of the relationship between small bowel (SB) lesions and FIT results. AIM: To determine whether SB lesions found by CE are associated with an increased rate of positive FIT. METHODS: Consecutive patients undergoing CE for obscure occult gastrointestinal bleeding also underwent FIT. CE was performed using the PillCam SB and FIT was performed with OC-Micro (three samples, threshold 75 and 100 ng/ml). RESULTS: Fifty-one patients were included; the mean lowest hemoglobin was 9.1 +/- 2.1 g/dl. Twenty-six patients (51.0%) had SB lesions identified by CE and were classified as the probable or suspected source of bleeding. At the threshold of 75 and 100 ng/ml, 12 of 26 (46.1%) and 10 of 26 (38.4%), respectively had a positive FIT. In contrast, only two of 25 (8.0%) patients without SB lesions had a positive FIT at both thresholds (P=0.002 and 0.010 respectively). The mean fecal hemoglobin in patients with SB lesions classified as probable or suspected source of bleeding versus patients with normal SB was 345.6 +/- 773 and 25.0 +/- 37.7 ng/ml, respectively (P=0.025). CONCLUSION: A positive FIT can be explained by significant SB lesions detected by CE. Further studies are still needed to evaluate whether asymptomatic patients with positive FIT and nonexplanatory colonoscopy should undergo further study of the SB. PMID- 21975697 TI - Percutaneous endoscopic gastrostomy tube occlusion in malignant peritoneal carcinomatosis-induced bowel obstruction. AB - OBJECTIVE: Percutaneous endoscopic gastrostomy (PEG) tube placement for decompression in advanced peritoneal carcinomatosis with bowel obstruction is a safe and feasible palliative procedure. We describe a rare, previously unreported phenomenon of PEG tube occlusion by gastric mucosal herniation. METHODS: A consecutive case series of 73 patients with advanced abdominal carcinomatosis induced bowel obstruction from January 2007 to June 2010. All patients had a 28 Fr (Bard) PEG tube placed for drainage. None of them were surgical candidates due to extensive peritoneal involvement. Patients with PEG tube occlusion as a result of gastric mucosal herniation were further evaluated. RESULTS: Nineteen patients were men and 54 were women. The mean age was 53.3 years. The most common cancer types were ovary, pancreas, colon, and stomach. All patients had PEG tube functioning well after the procedure with immediate relief of obstructive symptoms. Subsequently, 10 patients developed acute occlusion of PEG tubes with reoccurrence of obstructive symptoms. The time between the placement of the PEG tube and its occlusion ranged from 5 to 129 days. Repeat endoscopy showed the PEG tube occluded with gastric mucosa from the opposite wall. PEG tube was replaced with a 28 Fr balloon replacement tube leading to symptom improvement in all 10 patients. CONCLUSION: This rare but correctable phenomenon of obliteration of PEG tube from the gastric mucosa should be considered in any patient who develops intermittent occlusive symptoms. This phenomenon can be corrected by replacing the PEG tube with a ballooned replacement tube as well as occasional manipulation of the tube. PMID- 21975698 TI - DFT calculations of 29Si-NMR chemical shifts in Ru(II) silyl complexes: searching for trends and accurate values. AB - The (29)Si chemical shifts in a series of closely related Ru(II) silyl complexes have been calculated by DFT methods and compared to the experimental values. The factors that lead to possible discrepancies between experimental and calculated values have been identified. It is shown that it is necessary to include the spin orbit coupling associated with the relativistic effects of the heavy atoms for quantitative agreement with observed chemical shifts but trends are reasonably reproduced when the calculations do not include this correction. An NBO analysis of the NMR contributions from the bonds to Si and the Si core shows the greater importance of the former and a fine tuning originating from the latter. PMID- 21975699 TI - Sharpening the focus on systems-based practice. PMID- 21975701 TI - Charting the road to competence: developmental milestones for internal medicine residency training. AB - BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) Outcome Project requires that residency program directors objectively document that their residents achieve competence in 6 general dimensions of practice. INTERVENTION: In November 2007, the American Board of Internal Medicine (ABIM) and the ACGME initiated the development of milestones for internal medicine residency training. ABIM and ACGME convened a 33-member milestones task force made up of program directors, experts in evaluation and quality, and representatives of internal medicine stakeholder organizations. This article reports on the development process and the resulting list of proposed milestones for each ACGME competency. OUTCOMES: The task force adopted the Dreyfus model of skill acquisition as a framework the internal medicine milestones, and calibrated the milestones with the expectation that residents achieve, at a minimum, the "competency" level in the 5-step progression by the completion of residency. The task force also developed general recommendations for strategies to evaluate the milestones. DISCUSSION: The milestones resulting from this effort will promote competency-based resident education in internal medicine, and will allow program directors to track the progress of residents and inform decisions regarding promotion and readiness for independent practice. In addition, the milestones may guide curriculum development, suggest specific assessment strategies, provide benchmarks for resident self-directed assessment-seeking, and assist remediation by facilitating identification of specific deficits. Finally, by making explicit the profession's expectations for graduates and providing a degree of national standardization in evaluation, the milestones may improve public accountability for residency training. PMID- 21975702 TI - Centralized assessment in graduate medical education: cents and sensibilities. AB - RATIONALE: The start of residency represents an "educational handoff." Accreditation and credentialing organizations have called for better assessments of learner and patient outcomes and improved patient safety and quality of care. INTERVENTION: We describe the development of centralized assessments of baseline, core residency competencies at 2 institutions, and summarize principles and lessons learned for other institutions interested in developing similar interventions. RESULTS: At one institution, 70% of 1 083 new residents assessed via the Objective Standardized Clinical Examination stated they learned a new skill; 80% believe it was a useful way to spend orientation; 78% felt better prepared for aspects of internship; and 80% would recommend it for next year's interns. High levels of satisfaction are expressed by participants at the other institution, especially with the immediate provision of feedback after each station. At this institution, average new resident performance in the communication skills domain approached 90%, but patient care domain scores showed wide variability. The lowest scores were related to performing the psychomotor skills of aseptic technique. DISCUSSION: From a patient safety perspective, results suggest a need to improve the preparation of new residents, along with careful supervision of their early clinical work. The presence of skill deficits likely adds to the highly stressful transition into residency. Teaching institutions may use centralized assessment to enhance education and patient safety and to promote accountability to accrediting bodies, residents, and patients. The approach may identify gaps in the undergraduate curriculum. The addition of hand hygiene and aseptic technique teaching and assessment modules are currently being piloted at each of the institutions. PMID- 21975703 TI - Commentary: centralized assessment in graduate medical education: how can it help us reinvent training? PMID- 21975704 TI - Assessing intern core competencies with an objective structured clinical examination. AB - BACKGROUND: Residents are evaluated using Accreditation Council for Graduate Medical Education (ACGME) core competencies. An Objective Structured Clinical Examination (OSCE) is a potential evaluation tool to measure these competencies and provide outcome data. OBJECTIVE: Create an OSCE to evaluate and demonstrate improvement in intern core competencies of patient care, medical knowledge, practice-based learning and improvement, interpersonal and communication skills, professionalism, and systems-based practice before and after internship. METHODS: From 2006 to 2008, 106 interns from 10 medical specialties were evaluated with a preinternship and postinternship OSCE at Madigan Army Medical Center. The OSCE included eight 12-minute stations that collectively evaluated the 6 ACGME core competencies using human patient simulators, standardized patients, and clinical scenarios. Interns were scored using objective and subjective criteria, with a maximum score of 100 for each competency. Stations included death notification, abdominal pain, transfusion consent, suture skills, wellness history, chest pain, altered mental status, and computer literature search. These stations were chosen by specialty program directors, created with input from board-certified specialists, and were peer reviewed. RESULTS: All OSCE testing on the 106 interns (ages 25 to 44 [average, 28.6]; 70 [66%] men; 65 [58%] allopathic medical school graduates) resulted in statistically significant improvement in all ACGME core competencies: patient care (71.9% to 80.0%, P < .001), medical knowledge (59.6% to 78.6%, P < .001), practice-based learning and improvement (45.2% to 63.0%, P < .001), interpersonal and communication skills (77.5% to 83.1%, P < .001), professionalism (74.8% to 85.1%, P < .001), and systems-based practice (56.6% to 76.5%, P < .001). CONCLUSION: An OSCE during internship can evaluate incoming baseline ACGME core competencies and test for interval improvement. The OSCE is a valuable assessment tool to provide outcome measures on resident competency performance and evaluate program effectiveness. PMID- 21975705 TI - Vital signs: how early can resident evaluation predict acquisition of competency in surgical pathology? AB - OBJECTIVES: To determine whether a longitudinal, case-based evaluation system can predict acquisition of competency in surgical pathology and how trainees at risk can be identified early. DESIGN: Data were collected for trainee performance on surgical pathology cases (how well their diagnosis agreed with the faculty diagnosis) and compared with training outcomes. Negative training outcomes included failure to complete the residency, failure to pass the anatomic pathology component of the American Board of Pathology examination, and/or failure to obtain or hold a position immediately following training. FINDINGS: Thirty-three trainees recorded diagnoses for 54 326 surgical pathology cases, with outcome data available for 15 residents. Mean case-based performance was significantly higher for those with positive outcomes, and outcome status could be predicted as early as postgraduate year-1 (P = .0001). Performance on the first postgraduate year-1 rotation was significantly associated with the outcome (P = .02). Although trainees with unsuccessful outcomes improved their performance more rapidly, they started below residents with successful outcomes and did not make up the difference during training. There was no significant difference in Step 1 or 2 United States Medical Licensing Examination (USMLE) scores when compared with performance or final outcomes (P = .43 and P = .68, respectively) and the resident in-service examination (RISE) had limited predictive ability. DISCUSSION: Differences between successful- and unsuccessful outcome residents were most evident in early residency, ideal for designing interventions or counseling residents to consider another specialty. CONCLUSION: Our longitudinal case-based system successfully identified trainees at risk for failure to acquire critical competencies for surgical pathology early in the program. PMID- 21975706 TI - The development of a competency-based assessment rubric to measure resident milestones. AB - BACKGROUND: The outcomes-based assessment rubric is a novel systematic instrument for documenting improvement in clinical learning. APPROACH: This article describes the development of a rubric aimed at introducing specific performance indicators to measure the Accreditation Council for Graduate Medical Education competencies. RESULTS: The potential benefits and implications for medical education include specifying performance indicators and outcomes, ensuring that assessment is coherent and consistent for all residents, measuring resident outcomes based on real-life criteria, providing opportunities for residents to demonstrate proficiency in a specific competency and outcome level, and improving the quality of assessment. PMID- 21975707 TI - Systems-based practice defined: taxonomy development and role identification for competency assessment of residents. AB - PURPOSE: To demonstrate a methodology for coding and taxonomy development and to operationally define residents' competence in systems-based practice (SBP) in terms of observable roles, actions, and behaviors. METHODS: The Accreditation Council for Graduate Medical Education's (ACGME's) full-text definition of SBP and the 6 discrete expectations it contains were content analyzed. Structured interviews of 88 health care professionals using a variant of focus group interviews called nominal group processes were conducted and qualitatively analyzed to identify the key attributes of SBP. Themes obtained from these 2 procedures were conceptually matched and organized to create a taxonomy of observable SPB behaviors and the SBP domain. RESULTS: Six general resident roles emerged, under which 35 specific behavioral attributes were subsumed. From the SBP domain specified. Sample SBP items categorized by roles were derived that reflected "in-context" representations of ACGME SBP expectations. CONCLUSION: Our comprehensive analysis created an operational representation of the SBP competency. The taxonomy development model provides a framework for constructing assessment instrument(s) that could be applied to the other ACGME competencies or complex concepts in medical education. PMID- 21975708 TI - Training otologic surgical skills through simulation-moving toward validation: a pilot study and lessons learned. AB - INTRODUCTION: Methods for surgical education and training have changed little over the years. Recent calls to improve surgical efficiency and safety impose additional pressures that have an impact on surgical education and training. USE OF SIMULATION: Integration of data from advanced imaging technologies and computer technologies are creating simulation environments of unprecedented realism. Surgical education and training are poised to exploit low-cost simulation technologies to mitigate these pressures that are having an adverse impact on curricula. To become effective, simulation needs to undergo rigorous validation studies. INTERVENTION: With funding from that National Institute on Deafness and Other Communicative Disorders, we have embarked on a research design project to develop, disseminate, and validate a surgical system for use in otologic resident training and assessment and present key steps from this process. DISCUSSION: We discuss limiting factors related to technology and conducting multi-institutional studies, along with current developments to integrate curricula, as well as training and assessment capabilities in surgical education using simulation. PMID- 21975709 TI - Patient care management teams: improving continuity, office efficiency, and teamwork in a residency clinic. AB - BACKGROUND AND PROBLEM STATEMENT: The goals of the patient-centered medical home (PCMH) include the efficient and effective delivery of patient-centered care in the context of a continuity relationship. In residency training programs, competing demands on faculty, residents, and office staff create considerable challenge in demonstrating these vital attributes of the PCMH to residents. Given the emphasis on the PCMH, primary care residency programs need to strengthen the methods for teaching and modeling continuity, office efficiency, and team-based approaches to care. INTERVENTION: We designed and implemented a new system of "patient care management teams" in our family medicine residency and evaluated its impact on team members. Our quality improvement interventions included the creation of team structures linking faculty advisors and residents with patients, intrateam management of office tasks, and the implementation of multidisciplinary team meetings. EVALUATION: We surveyed faculty (n = 11), residents/fellows (n = 39), and staff (n = 12) before and at 2 points after the patient care management team interventions, and we collected patient satisfaction data during the intervention time period. RESULTS: The intervention resulted in significant improvements in perceptions of continuity of patient care, office efficiency, and team communication before and after the team interventions. During a 2-year period, the greatest improvements were in the areas of office efficiency and continuity of care. Independent patient satisfaction scores correlated with patient care management team improvements. CONCLUSIONS: Team structures, streamlined team-based management of routine office tasks, and consistent and frequent multidisciplinary meetings can improve the sense of continuity, office efficiency, and team collaboration in primary care residency clinics. PMID- 21975710 TI - Description of a developmental criterion-referenced assessment for promoting competence in internal medicine residents. AB - RATIONALE: End-of- rotation global evaluations can be subjective, produce inflated grades, lack interrater reliability, and offer information that lacks value. This article outlines the generation of a unique developmental criterion referenced assessment that applies adult learning theory and the learner, manager, teacher model, and represents an innovative application to the American Board of Internal Medicine (ABIM) 9-point scale. INTERVENTION: We describe the process used by Southern Illinois University School of Medicine to develop rotation-specific, criterion-based evaluation anchors that evolved into an effective faculty development exercise. RESULTS: The intervention gave faculty a clearer understanding of the 6 Accreditation Council for Graduate Medical Education competencies, each rotation's educational goals, and how rotation design affects meaningful work-based assessment. We also describe easily attainable successes in evaluation design and pitfalls that other institutions may be able to avoid. Shifting the evaluation emphasis on the residents' development of competence has made the expectations of rotation faculty more transparent, has facilitated conversations between program director and residents, and has improved the specificity of the tool for feedback. Our findings showed the new approach reduced grade inflation compared with the ABIM end-of-rotation global evaluation form. DISCUSSION: We offer the new developmental criterion-referenced assessment as a unique application of the competences to the ABIM 9-point scale as a transferable model for improving the validity and reliability of resident evaluations across graduate medical education programs. PMID- 21975711 TI - Development of the objective structured system-interaction examination. AB - STUDY OBJECTIVE: The purpose of this study was to develop an objective method of evaluating resident competency in systems-based practice. STUDY DESIGN: Faculty developed a 12-station examination, the Objective Structured System-Interaction Examination (OSSIE), patterned after the Objective Structured Clinical Examinations (OSCEs), to evaluate residents' ability to effectively work within the complex medical system of care. Scenarios consisted of multiple situations, such as patient hand-offs, consultations, complicated discharges, and family meetings, in which residents interacted with simulated professionals, simulated patients, and simulated family members to demonstrate the systems-based skills. Twelve second-year residents participated in the OSSIE. FINDINGS: Along with the standardized professionals, a faculty member provided the resident with immediate feedback and completed an evaluation form designed specifically to assess systems based practice. Residents, faculty, and staff evaluated the OSSIE and felt it provided a rich learning experience and was a beneficial means of formative assessment. The residents' third-year learning experiences were adapted to meet their needs, and suggestions were offered for curriculum revision. DISCUSSION: The OSSIE is unique in that it uses standardized professionals, involves scenarios in a variety of settings, and incorporates current technology, including an electronic health record and a state-of-the-art simulation laboratory, into the examination. Challenges to implementation include faculty time, scheduling of residents, and availability of resources. CONCLUSION: By using the OSSIE, faculty are able to assess, provide constructive feedback, and tailor training opportunities to improve resident competence in systems-based practice. Reliability and validity of an instrument developed for use with the OSSIE are currently being determined. PMID- 21975712 TI - Assessing colonoscopy training outcomes using quality indicators. AB - PURPOSE: Training numbers for colonoscopy vary among specialties. Tracking colonoscopy quality indicators for program graduates may provide reliable outcome data to improve educational programs and establish training requirements. The purpose of this study was to measure specific colonoscopy quality indicators for a family medicine graduate to determine if outcome can be used to assess the quality of procedure training and contribute to more objective means of establishing training numbers. METHODS: We present a case series of the first 800 colonoscopies performed by a newly credentialed family physician who had performed 101 procedures during residency training. Procedure reports and medical records were reviewed for all patients receiving a colonoscopy by this physician from September 2003 to September 2007. Selected quality indicators were compared to recommended colonoscopy standards. RESULTS: The overall reach-the-cecum rate was 98.6%. Adenomas were detected in 21.6% of females and 33.7% of males. All polyps measuring less than 2 cm were removed. Epinephrine was used for 3 patients with hemostasis after polypectomy. There were no perforations. CONCLUSIONS: Quality indicators for colonoscopy were met after 101 supervised procedures. Postgraduate tracking of nationally recognized colonoscopy quality indicators can provide valuable outcome data to improve residency training and assist in establishing uniform training requirements among specialties. PMID- 21975713 TI - Lessons learned from a 5-year experience with a 4-week experiential quality improvement curriculum in a preventive medicine fellowship. AB - BACKGROUND: Competency in practice-based learning and improvement (PBLI) and systems-based practice (SBP) empowers learners with the skills to plan, lead, and execute health care systems improvement efforts. Experiences from several graduate medical education programs describe the implementation of PBLI and SBP curricula as challenging because of lack of adequate curricular time and faculty resources, as well as a perception that PBLI and SBP are not relevant to future careers. A dedicated experiential rotation that requires fellow participation in a specialty-specific quality improvement project (QIP) may address some of these challenges. METHOD: We describe a retrospective analysis of our 5-year experience with a dedicated 3-week PBLI-SBP experiential curriculum in a preventive medicine fellowship program at Mayo Clinic, Rochester, Minnesota. RESULTS: Between 2004 and 2008, 19 learners including 7 preventive medicine fellows participated in the rotation. Using just-in-time learning, fellows work together on a relatively complex QIP of community or institutional significance. Since 2004, all 19 learners (100%) participating in this rotation have consistently demonstrated statistically significant increase in their quality improvement knowledge application tool (QIKAT) scores at the end of the rotation. At the end of the rotation, all 19 learners stated that they were either confident or very confident of making a change to improve health care in a local setting. Most of the QIPs resulted in sustainable practice improvements, and resultant solutions have been disseminated beyond the location of the original QIP. CONCLUSION: A dedicated experiential rotation that requires learner participation in a QIP is one of the effective methods to address the needs of the SBP and PBLI competencies. PMID- 21975714 TI - Commentary: principle-based teaching competencies. PMID- 21975715 TI - The virtual practice: using the residents' continuity clinic to teach practice management and systems-based practice. AB - BACKGROUND: Education in systems-based practice is a required component of all postgraduate medical education programs in the United States. Competency in this area requires that trainees have an understanding of the health care system sufficient to provide optimal care to patients. Most trainees in residency programs have little understanding of the complexities and challenges of present day practice in the current system of care and consider themselves unprepared to undertake this activity following completion of training. Training in practice management in residency programs has not been emphasized as an important component of systems-based practice. Historically, practice management training in residency programs has been done using a fully didactic model, and residents have expressed a desire to learn this skill by becoming more directly involved in the operations and management of a practice. The patient visit touches many aspects of the health care system, including clinic operations, insurance, quality, and finances. APPROACH: At our institution, we used the residents' continuity clinic practices as a vehicle to provide education in practice management and systems-based practice by creating a curriculum that included the residents' perceived gaps in knowledge regarding going into practice. This is known as the virtual practice. This curriculum is taught using data obtained from residents' practice to illustrate concepts in many areas, including primary practice operations, malpractice insurance, financial benchmarks, and career planning. RESULTS: Resident self-assessed knowledge of these areas increased after participating in the curriculum, and resident testimonials indicate satisfaction with the project. In addition, residents have become engaged and interested in how their effort translates into performance and how they participate in the health care system. PMID- 21975716 TI - Computer-enhanced visual learning method: a paradigm to teach and document surgical skills. AB - INNOVATION: Changes in health care are stimulating residency training programs to develop new methods for teaching surgical skills. We developed Computer-Enhanced Visual Learning (CEVL) as an innovative Internet-based learning and assessment tool. The CEVL method uses the educational procedures of deliberate practice and performance to teach and learn surgery in a stylized manner. AIM OF INNOVATION: CEVL is a learning and assessment tool that can provide students and educators with quantitative feedback on learning a specific surgical procedure. Methods involved examine quantitative data of improvement in surgical skills. Herein, we qualitatively describe the method and show how program directors (PDs) may implement this technique in their residencies. RESULTS: CEVL allows an operation to be broken down into teachable components. The process relies on feedback and remediation to improve performance, with a focus on learning that is applicable to the next case being performed. CEVL has been shown to be effective for teaching pediatric orchiopexy and is being adapted to additional adult and pediatric procedures and to office examination skills. The CEVL method is available to other residency training programs. PMID- 21975717 TI - Teaching error disclosure to residents: a curricular innovation and pilot study. AB - OBJECTIVE: To compare change in obstetrics and gynecology residents' self efficacy in disclosing medical errors after a formal educational session. METHODS: This was a retrospective postintervention survey to assess change in perceived preparedness to disclose medical errors. We used a 4-hour educational seminar that included a didactic component (30 minutes) and experiential learning with a trained facilitator (3 hours). Change in self-efficacy was measured using a 5-point Likert-type scale (1 is lowest, and 5 is highest) and was compared using sign test (alpha = .05). RESULTS: In our pilot study, 13 of 15 residents reported having previously participated in error disclosure. After the session, residents considered themselves more prepared for the following: to know what to include in and how to introduce error discussions, to deal with a patient's emotional reaction, to respond to a patient's questions regarding how an error occurred, and to recognize one's own emotions when discussing medical errors. Residents believed that they would be likely to use the skills learned in the remainder of residency and in their future career. CONCLUSIONS: This curriculum was associated with improvement in self-efficacy regarding error disclosure. Given the unique malpractice issues that obstetricians/gynecologists face, it seems particularly useful for residents to learn these skills early in their career. In addition, this topic represents an ideal educational opportunity for residencies to improve patient care and to address other core competencies in resident education such as communication skills and professionalism. PMID- 21975718 TI - Residents Learn to Improve Care Using the ACGME Core Competencies and Institute of Medicine Aims for Improvement: the Health Care Matrix. AB - OBJECTIVES: This article describes how internal medicine residents at Vanderbilt University Medical Center learn to assess and improve care using the Institute of Medicine aims for improvement and the Accreditation Council for Graduate Medical Education core competencies combined in a tool called the health care matrix. The most important and popular use of the health care matrix has been with suboptimal care, in which care is not safe, timely, effective, efficient, equitable, or patient centered. BACKGROUND: The core competencies provide a means of defining why care was not safe, timely, effective, efficient, equitable, or patient centered. The Institute of Medicine aims for improvement are also important because they are used to frame most publicly reported measures of quality. Few residents have an understanding of these public measures and how their futures will be affected by the growing trend toward quality report cards. INTERVENTION: To help the residents understand the significance of public measures of quality, they learn to assess their patients as a "panel," looking at the care they provide for patients with coronary artery disease and diabetes mellitus. Residents use the health care matrix to analyze 1 of their patients, and then as a group they select a health care matrix for their improvement project. The way the health care matrix is formatted and the sequencing of the core competencies allow for the analysis of the cells to lead to the final question "What was learned and what needs to be improved?" The residents are then taught the tools and methods of quality improvement and complete their project. Some of these projects have had a significant influence on external measures of quality for this organization. The article describes the 8-week course that residents complete, the use of the health care matrix, the analysis of the patient panel, and finally an example of a completed project in which they improve the timeliness of antibiotics administration to patients with pneumonia (a public measure of quality). PMID- 21975719 TI - A faculty and resident development program to improve learning and teaching skills. AB - OBJECTIVE: To assess the value of a faculty and resident medical education development program. STUDY DESIGN: Modules on Accreditation Council for Graduate Medical Education (ACGME) competencies and evaluation, teaching methods, and Residency Review Committee guidelines were created, beta tested, and installed on a website. Pretests and posttests were developed. Faculty and residents were required to complete the course. At initiation and 6 months after training, residents completed a feedback perception survey. Statistical analysis was performed using Student t test. P < .05 was considered significant. RESULTS: Forty-nine voluntary faculty members and residents completed the course. The posttest scores on all the ACGME competencies were significantly higher than the pretest scores (P < .05). The results of the residents' survey indicated that the educational development program significantly improved their perceptions of corrective and immediate feedback by faculty. CONCLUSION: A formal Internet-based program significantly increases short-term cognitive knowledge about the ACGME competencies among participants and improves trainees' perceptions of the quality of faculty feedback up to 6 months after training. PMID- 21975720 TI - Evaluation of a formal mentoring program in an obstetrics and gynecology residency training program: resident feedback and suggestions. AB - OBJECTIVE: A formal mentoring program for residents was introduced at our Department of Obstetrics and Gynecology in 2004. The objective of this study was to assess residents' attitudes toward and suggestions for the mentoring program. STUDY DESIGN/METHODS: An anonymous questionnaire with Likert-scaled questions on multiple areas of the program was distributed to all residents. The responses were scored with a rating of 0, 1, and 2, and mean ratings were calculated. RESULTS/CONCLUSIONS: The response rate was 28 of 40 (70.0%). Areas of the mentoring program deemed most important were "career planning" (mean score 1.85) and "scientific research" (1.51). The most negative aspects of the program were "lack of time" of the mentees (1.57) and the mentors (1.29). When matching mentees with mentors, the most important factors were "specialty/subspecialty" (1.71), "research interests"(1.65), "personality"(1.54), and the "ability to pick one's own mentor"(1.31). The majority of respondents (9 of 14, 64.3%) welcomed e mail reminders to set up meetings with their mentor. These data have resulted in significant changes in our mentoring program. Future directions include continued surveillance of our program and collaboration between different residency programs in order to maximize the benefit of the resident mentor program. PMID- 21975721 TI - Assessing patient safety culture of internal medicine house staff in an academic teaching hospital. AB - PURPOSE: Patient safety culture (PSC) examines how individuals perceive an organization's commitment and proficiency in health and safety management. The primary objective of this study was to assess hospital PSC from the perspective of internal medicine house staff, and to compare the results by postgraduate year (PGY) of training and to national hospital benchmark data. METHODS: The authors modified and used a version of the Hospital Survey on Patient Safety Culture (HSOPSC), which has 12 PSC dimensions. Each dimension uses a 5-level Likert scale of agreement ("Strongly disagree" to "Strongly agree") or frequency ("Never" to "Always"). The survey was distributed to 68 PGY-2 and PGY-3 internal medicine house staff at an academic medical center between December 2006 and February 2007. Composite scores were created for each respondent by calculating the proportion of positive responses for each domain. Domain score means were compared between PGYs and to survey data from hospitals that administered the HSOPSC (ie, benchmark data). RESULTS: The overall response rate was 85.3% (58/68). House staff scored lower on 6 and 4 of the 12 PSC dimensions, when compared with the overall national hospital and medicine unit benchmarks, respectively (P < .05). PGY-3 staff scored lower than PGY-2 staff in 2 dimensions (P < .05). CONCLUSIONS: PGY-2 and PGY-3 internal medicine house staff at our institution were in agreement on most of the PSC dimensions. Overall, house staff PSC was significantly lower than national hospital benchmark data for half of the dimensions. The results of this study will be used to establish internal PSC benchmarks and to identify targets for interventions to further improve PSC. PMID- 21975722 TI - Building faculty community: fellowship in graduate medical education administration. AB - INTRODUCTION: The Department of Graduate Medical Education at Stanford Hospital and Clinics has developed a professional training program for program directors. This paper outlines the goals, structure, and expected outcomes for the one-year Fellowship in Graduate Medical Education Administration program. BACKGROUND: The skills necessary for leading a successful Accreditation Council for Graduate Medical Education (ACGME) training program require an increased level of curricular and administrative expertise. To meet the ACGME Outcome Project goals, program directors must demonstrate not only sophisticated understanding of curricular design but also competency-based performance assessment, resource management, and employment law. Few faculty-development efforts adequately address the complexities of educational administration. As part of an institutional-needs assessment, 41% of Stanford program directors indicated that they wanted more training from the Department of Graduate Medical Education. INTERVENTION: To address this need, the Fellowship in Graduate Medical Education Administration program will provide a curriculum that includes (1) readings and discussions in 9 topic areas, (2) regular mentoring by the director of Graduate Medical Education (GME), (3) completion of a service project that helps improve GME across the institution, and (4) completion of an individual scholarly project that focuses on education. RESULTS: The first fellow was accepted during the 2008 2009 academic year. Outcomes for the project include presentation of a project at a national meeting, internal workshops geared towards disseminating learning to peer program directors, and the completion of a GME service project. The paper also discusses lessons learned for improving the program. PMID- 21975723 TI - Demographic and work-life study of chief residents: a survey of the program directors in internal medicine residency programs in the United States. AB - CONTEXT: Chief residents play a crucial role in internal medicine residency programs in administration, academics, team building, and coordination between residents and faculty. The work-life and demographic characteristics of chief residents has not been documented. OBJECTIVE: To delineate the demographics and day-to-day activities of chief residents. DESIGN, SETTING, AND PARTICIPANTS: The Survey Committee of the Association of Program Directors in Internal Medicine (APDIM) developed a Web-based questionnaire. A link was sent in November 2006 by e-mail to 381 member programs (98%). Data collection ended in April 2007. MEASUREMENTS: Data collected include the number of chief residents per residency, the ratio of chief residents per resident, demographics, and information on salary/benefits, training and mentoring, and work life. RESULTS: The response rate was 62% (N = 236). There was a mean of 2.5 chief residents per program, and on average there was 1 chief resident for 17.3 residents. Of the chief residents, 40% were women, 38% international medical graduates, and 11% minorities. Community-based programs had a higher percentage of postgraduate year 3 (PGY-3)-level chief residents compared to university-based programs (22% versus 8%; P = .02). Mean annual salary was $60 000, and the added value of benefits was $21 000. Chief residents frequently supplement their salaries through moonlighting. The majority of formal training occurs by attending APDIM meetings. Forty-one percent of programs assign academic rank to chief residents. CONCLUSION: Most programs have at least 2 chief residents and expect them to perform administrative functions, such as organizing conferences. Most programs evaluate chief residents regularly in administration, teaching, and clinical skills. PMID- 21975725 TI - International Medical Education Outreach: Benefits for US Medical Education and Practice: An Interview with Joseph Kolars, MD. PMID- 21975724 TI - Achieving the AAAs of Ambulatory Care: Aptitude, Appeal, and Appreciation. AB - BACKGROUND: In the current health care environment more patient care has moved from in-hospital care to the ambulatory primary care settings; however, fewer internal medicine residents are pursuing primary care careers. Barriers to residents developing a sense of competency and enjoyment in ambulatory medicine include the complexity of practice-based systems, patients with multiple chronic diseases, and the limited time that residents spend in the outpatient setting. OBJECTIVE: In an effort to accelerate residents' ambulatory care competence and enhance their satisfaction with ambulatory practice, we sought to change the learning environment. Interns were provided a series of intensive, focused, ambulatory training sessions prior to beginning their own continuity clinic sessions. The sessions were designed to enable them to work confidently and effectively in their continuity clinic from the beginning of the internship year, and it was hoped this would have a positive impact on their perception of the desirability of ambulatory practice. METHODS: Improvement needs assessment after a performance, so we developed a structured, competency-based, multidisciplinary curriculum for initiation into ambulatory practice. The curriculum focused on systems-based practice, patient safety, quality improvement, and collaborative work while emphasizing the importance of continuity of care and long-term doctor patient relationships. Direct observation of patient encounters was done by an attending physician to evaluate communication and physical examination skills. Systems of care commonly used in the clinic were demonstrated. Resources for practice-based learning were used. CONCLUSION: The immersion of interns in an intensive, hands-on experience using a structured ambulatory care orientation curriculum early in training may prepare the intern to be a successful provider and learner in the primary care ambulatory setting. PMID- 21975726 TI - Communities of practice and learning: disseminating their work. PMID- 21975727 TI - Assessing duty hour compliance: practical lessons for programs and institutions. PMID- 21975728 TI - Inhibition of nicotinamide phosphoribosyltransferase modifies LPS-induced inflammatory responses of human monocytes. AB - Recent studies have identified enzymes that use NAD as a substrate, thus contributing to its net consumption. To maintain the intracellular pool, NAD is re-synthesized by a salvage pathway using nicotinamide, the by-product generated by the enzymatic cleavage of NAD. Enzymes involved in NAD re-synthesis include nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase. Our studies show, that NAMPT was substantially up-regulated by LPS in primary human monocytes, suggesting that it may be especially required during the process of monocyte activation. To evaluate the contribution of the NAD rescue pathway to LPS-induced biological responses in human monocytes, we used APO866, a well-characterized inhibitor of NAMPT. Concomitant with the inhibition of NAMPT, LPS-induced TNF-alpha protein synthesis declined, while TNF alpha mRNA levels were minimally affected. Moreover, APO866 strongly decreased the production of reactive oxygen species (ROS), increased surface expression of the NAD-consuming enzyme CD38, and modified the production of selective eicosanoids. We further demonstrate that protein ADP-ribosylation was strongly reduced, indicating a possible link between this post-translational protein modification and human monocyte inflammatory responses. Despite a substantial reduction in intracellular NAD levels, activated monocytes were resistant to apoptosis, while resting monocytes were not. Taken together, our data suggest that activated monocytes strongly depend on the NAD salvage pathway to mount an appropriate inflammatory response. Their survival is not affected by NAD depletion, probably as a result of LPS-mediated anti-apoptotic signals. PMID- 21975729 TI - Assessment of wearable global positioning system units for physical activity research. AB - BACKGROUND: Responding to the growing interest in the environmental influences on physical activity, and the concerns about the limitations of self-report data, this study evaluates Global Positioning System (GPS) units for measuring outdoor physical activity. METHODS: Four GPS models were selected to test their accuracy related to adherence to an actual route walked, variations based on position of unit on user's body, and variations against a known geodetic point. A qualitative assessment was performed using the following criteria: a) battery life, b) memory capacity, c) initial satellite signal acquisition time, d) ease of data transfer to other programs, e) wearability, f) ease of operation, g) suitability for specific study populations, and h) price. RESULTS AND CONCLUSIONS: The Garmin Forerunner provided the most accurate data for data points collected along a known route. Comparisons based on different body placement of units showed some variations. GlobalSat reported battery life of 24 hours, compared with 9-15 hours for the other units. The static test using ANOVA showed that the Garmin Foretrex's data points compared with a geodetic point was significantly more accurate than the other 3 models. GPS units appear promising as a tool to capture objective data on outdoor physical activities. PMID- 21975730 TI - Oral steroids for long-term use in cystic fibrosis. AB - BACKGROUND: In cystic fibrosis (CF) airway obstruction and recurrent respiratory infection lead to inflammation, long-term lung damage, respiratory failure and death. Anti-inflammatory agents, e.g. oral corticosteroids are used since inflammation occurs early in disease. OBJECTIVES: To assess the effectiveness of oral corticosteroids in respiratory complications in CF, particularly lung function and adverse events. We examined long-term use (over 30 days) only. SEARCH STRATEGY: We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 06 April 2011. SELECTION CRITERIA: Randomised trials comparing oral corticosteroids given for more than 30 days with placebo or no additional therapy in people with CF. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility and quality. MAIN RESULTS: Of nine studies identified, three (354 participants) were included: two with four year follow up and one with 12-weeks follow up. Data were lacking on predefined outcomes; common outcomes were examined at different time-points and presented differently. Meta-analyses were not possible.In one study, oral corticosteroids at prednisolone-equivalent dose of 1 mg/kg alternate days slowed progression of lung disease; at two and four years, % predicted FEV(1) in the 1 mg/kg group changed significantly more than in the placebo group (P < 0.02). During the first two years, the 2 mg/kg group was not significantly different from the placebo group. Linear growth retardation was observed from six months in the 2 mg/kg alternate days prednisolone group and from 24 months in the 1 mg/kg alternate days prednisolone group.Adverse events terminated one four-year study early. Year 10 follow up showed catch-up growth started two years after treatment ceased. Alternate-day treatment with oral corticosteroids may have impaired growth until adulthood in boys. AUTHORS' CONCLUSIONS: Oral corticosteroids at prednisolone equivalent dose of 1 to 2 mg/kg alternate days appear to slow progression of lung disease in CF; benefit should be weighed against occurrence of adverse events. Risk-benefit analysis of low-dose alternate days corticosteroids is important and the short-term use of oral corticosteroids should be better evaluated. PMID- 21975731 TI - Vitamin A supplementation to prevent mortality and short- and long-term morbidity in very low birthweight infants. AB - BACKGROUND: Vitamin A is necessary for normal lung growth and the integrity of respiratory tract epithelial cells. Preterm infants have low vitamin A status at birth, and this has been associated with increased risk of developing chronic lung disease. OBJECTIVES: To evaluate vitamin A supplementation on the incidence of death and/or neonatal chronic lung disease and long-term neurodevelopmental disability in very low birthweight infants (VLBW); and to consider the effect of the supplementation route, dose, and timing. SEARCH STRATEGY: In August 2011, the Cochrane Central Regsiter of Controlled Trials (Central, The Cochrane Library), MEDLINE, Science Citation Index and the Oxford Database of Perinatal Trials were searched. The reference lists of relevant trials, paediatric and nutrition journals, and conference abstracts and proceedings were handsearched up to 2007. SELECTION CRITERIA: Randomised controlled trials comparing vitamin A supplementation with a control (placebo or no supplementation) or other dosage regimens in VLBW infants (birthweight <= 1500 g or < 32 weeks' gestation). DATA COLLECTION AND ANALYSIS: Both review authors screened the search results, extracted data, and assessed the trials' risk of bias. Results were reported as risk ratios (RR), risk differences (RD), and number needed to treat to benefit (NNTB), all with 95% confidence intervals (CI). Trialists were contacted for additional data. MAIN RESULTS: Nine trials met the inclusion criteria, eight compared vitamin A supplementation with a control (1291 infants), and one compared different regimens (120 infants). Compared to the control group, vitamin A appears to be beneficial in reducing death or oxygen requirement at one month of age (RR 0.93, 95% CI 0.88 to 0.99; RD -0.05, 95% CI -0.10 to -0.01; NNTB 20, 95% CI 10 to 100; 1165 infants) and oxygen requirement at 36 weeks' postmenstrual age (RR 0.87, 95% CI 0.77 to 0.98; RD -0.08, 95% CI -0.14 to -0.01; NNTB 13, 95% CI 7 to 100; 824 infants). A trend towards a reduction in death or oxygen requirement at 36 weeks' postmenstrual age was also noted (RR 0.91, 95% CI 0.82 to 1.00; 1001 infants). Neurodevelopmental assessment of 88% of surviving infants in the largest trial showed no differences between the groups at 18 to 22 months of age, corrected for prematurity. The different dosage vitamin A regimens showed similar results. AUTHORS' CONCLUSIONS: Whether clinicians decide to utilise repeat intramuscular doses of vitamin A to prevent chronic lung disease may depend upon the local incidence of this outcome and the value attached to achieving a modest reduction in this outcome, balanced against the lack of other proven benefits and the acceptability of treatment. Information on long-term neurodevelopmental status suggests no evidence of either benefit or harm from the intervention. PMID- 21975732 TI - Human albumin solution for resuscitation and volume expansion in critically ill patients. AB - BACKGROUND: Human albumin solutions are used for a range of medical and surgical problems. Licensed indications are the emergency treatment of shock and other conditions where restoration of blood volume is urgent, such as in burns and hypoproteinaemia. Human albumin solutions are more expensive than other colloids and crystalloids. OBJECTIVES: To quantify the effect on mortality of human albumin and plasma protein fraction (PPF) administration in the management of critically ill patients. SEARCH STRATEGY: We searched the Cochrane Injuries Group Specialised Register (searched 31 May 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE (Ovid) (1948 to week 3 May 2011), EMBASE (Ovid) (1980 to Week 21 2011), CINAHL (EBSCO) (1982 to May 2011), ISI Web of Science: Science Citation Index Expanded (SCI EXPANDED) (1970 to May 2011), ISI Web of Science: Conference Proceedings Citation Index - Science (CPCI-S) (1990 to May 2011), PubMed (www.ncbi.nlm.nih.gov/sites/entrez/) (searched 10 June 2011, limit: last 60 days). Reference lists of trials and review articles were checked, and authors of identified trials were contacted. SELECTION CRITERIA: Randomised controlled trials comparing albumin or PPF with no albumin or PPF or with a crystalloid solution in critically ill patients with hypovolaemia, burns or hypoalbuminaemia. DATA COLLECTION AND ANALYSIS: We collected data on the participants, albumin solution used, mortality at the end of follow up, and quality of allocation concealment. Analysis was stratified according to patient type. MAIN RESULTS: We found 38 trials meeting the inclusion criteria and reporting death as an outcome. There were 1,958 deaths among 10,842 trial participants.For hypovolaemia, the relative risk of death following albumin administration was 1.02 (95% confidence interval (CI) 0.92 to 1.13). This estimate was heavily influenced by the results of the SAFE trial, which contributed 75.2% of the information (based on the weights in the meta-analysis). For burns, the relative risk was 2.93 (95% CI 1.28 to 6.72) and for hypoalbuminaemia the relative risk was 1.26 (95% CI 0.84 to 1.88). There was no substantial heterogeneity between the trials in the various categories (Chi(2) = 26.66, df = 31, P = 0.69). The pooled relative risk of death with albumin administration was 1.05 (95% CI 0.95 to 1.16). AUTHORS' CONCLUSIONS: For patients with hypovolaemia, there is no evidence that albumin reduces mortality when compared with cheaper alternatives such as saline. There is no evidence that albumin reduces mortality in critically ill patients with burns and hypoalbuminaemia. The possibility that there may be highly selected populations of critically ill patients in which albumin may be indicated remains open to question. However, in view of the absence of evidence of a mortality benefit from albumin and the increased cost of albumin compared to alternatives such as saline, it would seem reasonable that albumin should only be used within the context of well concealed and adequately powered randomised controlled trials. PMID- 21975733 TI - Decision aids for people facing health treatment or screening decisions. AB - BACKGROUND: Decision aids prepare people to participate in decisions that involve weighing benefits, harms, and scientific uncertainty. OBJECTIVES: To evaluate the effectiveness of decision aids for people facing treatment or screening decisions. SEARCH STRATEGY: For this update, we searched from January 2006 to December 2009 in MEDLINE (Ovid); Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, issue 4 2009); CINAHL (Ovid) (to September 2008 only); EMBASE (Ovid); PsycINFO (Ovid); and grey literature. Cumulatively, we have searched each database since its start date. SELECTION CRITERIA: We included published randomised controlled trials (RCTs) of decision aids, which are interventions designed to support patients' decision making by providing information about treatment or screening options and their associated outcomes, compared to usual care and/or alternative interventions. We excluded studies in which participants were not making an active treatment or screening decision. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts for inclusion, extracted data, and assessed potential risk of bias. The primary outcomes, based on the International Patient Decision Aid Standards, were:A) decision attributes;B) decision making process attributes.Secondary outcomes were behavioral, health, and health system effects. We pooled results of RCTs using mean differences (MD) and relative risks (RR), applying a random effects model. MAIN RESULTS: Of 34,316 unique citations, 86 studies involving 20,209 participants met the eligibility criteria and were included. Thirty-one of these studies are new in this update. Twenty-nine trials are ongoing. There was variability in potential risk of bias across studies. The two criteria that were most problematic were lack of blinding and the potential for selective outcome reporting, given that most of the earlier trials were not registered.Of 86 included studies, 63 (73%) used at least one measure that mapped onto an IPDAS effectiveness criterion: A) criteria involving decision attributes: knowledge scores (51 studies); accurate risk perceptions (16 studies); and informed value based choice (12 studies); and B) criteria involving decision process attributes: feeling informed (30 studies) and feeling clear about values (18 studies).A) Criteria involving decision attributes:Decision aids performed better than usual care interventions by increasing knowledge (MD 13.77 out of 100; 95% confidence interval (CI) 11.40 to 16.15; n = 26). When more detailed decision aids were compared to simpler decision aids, the relative improvement in knowledge was significant (MD 4.97 out of 100; 95% CI 3.22 to 6.72; n = 15). Exposure to a decision aid with expressed probabilities resulted in a higher proportion of people with accurate risk perceptions (RR 1.74; 95% CI 1.46 to 2.08; n = 14). The effect was stronger when probabilities were expressed in numbers (RR 1.93; 95% CI 1.58 to 2.37; n = 11) rather than words (RR 1.27; 95% CI 1.09 to 1.48; n = 3). Exposure to a decision aid with explicit values clarification compared to those without explicit values clarification resulted in a higher proportion of patients achieving decisions that were informed and consistent with their values (RR 1.25; 95% CI 1.03 to 1.52; n = 8).B) Criteria involving decision process attributes:Decision aids compared to usual care interventions resulted in: a) lower decisional conflict related to feeling uninformed (MD -6.43 of 100; 95% CI 9.16 to -3.70; n = 17); b) lower decisional conflict related to feeling unclear about personal values (MD -4.81; 95% CI -7.23 to -2.40; n = 14); c) reduced the proportions of people who were passive in decision making (RR 0.61; 95% CI 0.49 to 0.77; n = 11); and d) reduced proportions of people who remained undecided post-intervention (RR 0.57; 95% CI 0.44 to 0.74; n = 9). Decision aids appear to have a positive effect on patient-practitioner communication in the four studies that measured this outcome. For satisfaction with the decision (n = 12) and/or the decision making process (n = 12), those exposed to a decision aid were either more satisfied or there was no difference between the decision aid versus comparison interventions. There were no studies evaluating the decision process attributes relating to helping patients to recognize that a decision needs to be made or understand that values affect the choice.C) Secondary outcomesExposure to decision aids compared to usual care continued to demonstrate reduced choice of: major elective invasive surgery in favour of conservative options (RR 0.80; 95% CI 0.64 to 1.00; n = 11). Exposure to decision aids compared to usual care also resulted in reduced choice of PSA screening (RR 0.85; 95% CI 0.74 to 0.98; n = 7). When detailed compared to simple decision aids were used, there was reduced choice of menopausal hormones (RR 0.73; 95% CI 0.55 to 0.98; n = 3). For other decisions, the effect on choices was variable. The effect of decision aids on length of consultation varied from -8 minutes to +23 minutes (median 2.5 minutes). Decision aids do not appear to be different from comparisons in terms of anxiety (n = 20), and general health outcomes (n = 7), and condition specific health outcomes (n = 9). The effects of decision aids on other outcomes (adherence to the decision, costs/resource use) were inconclusive. AUTHORS' CONCLUSIONS: New for this updated review is evidence that: decision aids with explicit values clarification exercises improve informed values-based choices; decision aids appear to have a positive effect on patient-practitioner communication; and decision aids have a variable effect on length of consultation.Consistent with findings from the previous review, which had included studies up to 2006: decision aids increase people's involvement, and improve knowledge and realistic perception of outcomes; however, the size of the effect varies across studies. Decision aids have a variable effect on choices. They reduce the choice of discretionary surgery and have no apparent adverse effects on health outcomes or satisfaction. The effects on adherence with the chosen option, patient-practitioner communication, cost-effectiveness, and use with developing and/or lower literacy populations need further evaluation. Little is known about the degree of detail that decision aids need in order to have positive effects on attributes of the decision or decision-making process. PMID- 21975734 TI - Venepuncture versus heel lance for blood sampling in term neonates. AB - BACKGROUND: Heel lance has been the conventional method of blood sampling in neonates for screening tests. Neonates undergoing heel lance experience pain which cannot be completely alleviated. OBJECTIVES: To determine whether venepuncture or heel lance is less painful and more effective for blood sampling in term neonates. SEARCH STRATEGY: Randomized or quasi-randomised controlled trials comparing pain response to venepuncture versus heel lance were identified by searching the Cochrane Central Regsiter of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, EMBASE, CINAHL, and clinical trials registries in May 2011. SELECTION CRITERIA: Trials comparing pain response to venepuncture versus heel lance with or with out the use of a sweet tasting solution as a co intervention in term neonates. DATA COLLECTION AND ANALYSIS: Outcomes included pain response to venepuncture versus heel lance with or without the use of a sweet tasting solution using validated pain measures, the need of repeat sampling and cry characteristics. Analyses included typical relative risk (RR), risk difference (RD), number needed to treat (NNT), weighted mean difference (WMD) and standardized mean difference (SMD) with their 95% confidence intervals (CI). Between study heterogeneity was reported including the I squared (I(2)) test. MAIN RESULTS: Six studies (n = 478) of variable quality were included. A composite outcome of Infant Pain Scale (NIPS), Neonatal Facial Action Coding System (NFCS) and/or Premature Infant Pain Profile (PIPP) score was reported in 288 infants, who did not receive a sweet tasting solution. Meta-analysis showed a significant reduction in the venepuncture versus the heel lance group (SMD -0.76, 95% CI -1.00 to -0.52; I(2) = 0%). When a sweet tasting solution was provided the SMD remained significant favouring the venepuncture group (SMD - 0.38, 95% CI 0.69 to -0.07). The typical RD for requiring more than one skin puncture for venepuncture versus heel lance (reported in 4 studies; n = 254) was -0.34 (95% CI -0.43 to -0.25; I(2) = 97%). The NNT to avoid one repeat skin puncture was 3 (95% CI 2 to 4). Cry characteristics favoured the venepuncture group but the differences were reduced by the provision of sweet tasting solutions prior to either procedure. AUTHORS' CONCLUSIONS: Venepuncture, when performed by a skilled phlebotomist, appears to be the method of choice for blood sampling in term neonates. The use of a sweet tasting solution further reduces the pain.Further well designed randomised controlled trials should be conducted in settings where several individuals perform the procedures. PMID- 21975735 TI - Treatments for iron-deficiency anaemia in pregnancy. AB - BACKGROUND: Iron deficiency, the most common cause of anaemia in pregnancy worldwide, can be mild, moderate or severe. Severe anaemia can have very serious consequences for mothers and babies, but there is controversy about whether treating mild or moderate anaemia provides more benefit than harm. OBJECTIVES: To assess the effects of different treatments for anaemia in pregnancy attributed to iron deficiency (defined as haemoglobin less than 11 g/dL or other equivalent parameters) on maternal and neonatal morbidity and mortality. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (7 June 2011), CENTRAL (2011, Issue 5), PubMed (1966 to June 2011), the International Clinical Trials Registry Platform (ICTRP) (2 May 2011), Health Technology Assessment Program (HTA) (2 May 2011) and LATINREC (Colombia) (2 May 2011). SELECTION CRITERIA: Randomised controlled trials comparing treatments for anaemia in pregnancy attributed to iron deficiency. DATA COLLECTION AND ANALYSIS: We identified 23 trials, involving 3.198 women. We assessed their risk of bias. Three further studies identified are awaiting classification. MAIN RESULTS: Many of the trials were from low-income countries; they were generally small and frequently methodologically poor. They covered a very wide range of differing drugs, doses and routes of administration, making it difficult to pool data. Oral iron in pregnancy showed a reduction in the incidence of anaemia (risk ratio 0.38, 95% confidence interval 0.26 to 0.55, one trial, 125 women) and better haematological indices than placebo (two trials). It was not possible to assess the effects of treatment by severity of anaemia. A trend was found between dose and reported adverse effects. Most trials reported no clinically relevant outcomes nor adverse effects. Although the intramuscular and intravenous routes produced better haematological indices in women than the oral route, no clinical outcomes were assessed and there were insufficient data on adverse effects, for example, on venous thrombosis and severe allergic reactions. Daily low-dose iron supplements may be effective at treating anaemia in pregnancy with less gastrointestinal side effects compared with higher doses. AUTHORS' CONCLUSIONS: Despite the high incidence and burden of disease associated with this condition, there is a paucity of good quality trials assessing clinical maternal and neonatal effects of iron administration in women with anaemia. Daily oral iron treatment improves haematological indices but causes frequent gastrointestinal adverse effects. Parenteral (intramuscular and intravenous) iron enhances haematological response, compared with oral iron, but there are concerns about possible important adverse effects (for intravenous treatment venous thrombosis and allergic reactions and for intramuscular treatment important pain, discolouration and allergic reactions). Large, good quality trials, assessing clinical outcomes (including adverse effects) as well as the effects of treatment by severity of anaemia are required. PMID- 21975737 TI - Exercise training for adults with chronic kidney disease. AB - BACKGROUND: Chronic kidney disease (CKD) is a worldwide public health problem. In the National Kidney Foundation Disease Outcomes Quality Initiative guidelines it is stressed that lifestyle issues such as physical activity should be seen as cornerstones of the therapy. The physical fitness in adults with CKD is so reduced that it impinges on ability and capacity to perform activities in everyday life and occupational tasks. An increasing number of studies have been published regarding health effects of various regular exercise programmes in adults with CKD and in renal transplant patients. OBJECTIVES: We aimed to: 1) assess the effects of regular exercise in adults with CKD and kidney transplant patients; and 2) determine how the exercise programme should be designed (e.g. type, duration, intensity, frequency of exercise) to be able to affect physical fitness and functioning, level of physical activity, cardiovascular dimensions, nutrition, lipids, glucose metabolism, systemic inflammation, muscle morphology and morphometrics, dropout rates, compliance, adverse events and mortality. SEARCH STRATEGY: We searched the Cochrane Renal Group's specialised register, CENTRAL, MEDLINE, EMBASE, CINAHL, Web of Science, Biosis, Pedro, Amed, AgeLine, PsycINFO and KoreaMed. We also handsearched reference lists of review articles and included studies, conference proceeding's abstracts. There were no language restrictions.Date of last search: May 2010. SELECTION CRITERIA: We included any randomised controlled trial (RCT) enrolling adults with CKD or kidney transplant recipients undergoing any type of physical exercise intervention undertaken for eight weeks or more. Studies using less than eight weeks exercise, those only recommending an increase in physical activity, and studies in which co interventions are not applied or given to both groups were excluded. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of study and data quality were performed independently by the two authors. Continuous outcome data are presented as standardised mean difference (SMD) or mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS: Forty-five studies, randomising 1863 participants were included in this review. Thirty two studies presented data that could be meta-analysed. Types of exercise training included cardiovascular training, mixed cardiovascular and resistance training, resistance-only training and yoga. Some studies used supervised exercise interventions and others used unsupervised interventions. Exercise intensity was classed as 'high' or 'low', duration of individual exercise sessions ranged from 20 minutes/session to 110 minutes/session, and study duration was from two to 18 months. Seventeen per cent of studies were classed as having an overall low risk of bias, 33% as moderate, and 49% as having a high risk of bias.The results shows that regular exercise significantly improved: 1) physical fitness (aerobic capacity, 24 studies, 847 participants: SMD -0.56, 95% CI -0.70 to -0.42; walking capacity, 7 studies, 191 participants: SMD -0.36, 95% CI-0.65 to -0.06); 2) cardiovascular dimensions (resting diastolic blood pressure, 11 studies, 419 participants: MD 2.32 mm Hg, 95% CI 0.59 to 4.05; resting systolic blood pressure, 9 studies, 347 participants: MD 6.08 mm Hg, 95% CI 2.15 to 10.12; heart rate, 11 studies, 229 participants: MD 6 bpm, 95% CI 10 to 2); 3) some nutritional parameters (albumin, 3 studies, 111 participants: MD -2.28 g/L, 95% CI -4.25 to -0.32; pre-albumin, 3 studies, 111 participants: MD - 44.02 mg/L, 95% CI -71.52 to -16.53; energy intake, 4 studies, 97 participants: SMD -0.47, 95% CI -0.88 to -0.05); and 4) health-related quality of life. Results also showed how exercise should be designed in order to optimise the effect. Other outcomes had insufficient evidence. AUTHORS' CONCLUSIONS: There is evidence for significant beneficial effects of regular exercise on physical fitness, walking capacity, cardiovascular dimensions (e.g. blood pressure and heart rate), health-related quality of life and some nutritional parameters in adults with CKD. Other outcomes had insufficient evidence due to the lack of data from RCTs. The design of the exercise intervention causes difference in effect size and should be considered when prescribing exercise with the aim of affecting a certain outcome. Future RCTs should focus more on the effects of resistance training interventions or mixed cardiovascular- and resistance training as these exercise types have not been studied as much as cardiovascular exercise. PMID- 21975736 TI - Adjuvant chemotherapy for endometrial cancer after hysterectomy. AB - BACKGROUND: Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. OBJECTIVES: To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. DATA COLLECTION AND ANALYSIS: We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. MAIN RESULTS: Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly favouring the addition of postoperative platinum based chemotherapy. The HR for progression-free survival is 0.75 (0.64 to 0.89). This means that chemotherapy reduces the risk of being dead at any censorship by a quarter. Chemotherapy reduces the risk of developing the first recurrence outside the pelvis (RR = 0.79 (0.68 to 0.92), 5% absolute risk reduction; NNT = 20). The analysis of pelvic recurrence rates is underpowered but the trend suggests that chemotherapy may be less effective than radiotherapy in a direct comparison (RR = 1.28 (0.97 to 1.68)) but it may have added value when used with radiotherapy (RR = 0.48 (0.20 to 1.18)). AUTHORS' CONCLUSIONS: Postoperative platinum based chemotherapy is associated with a small benefit in progression free survival and overall survival irrespective of radiotherapy treatment. It reduces the risk of developing a metastasis, could be an alternative to radiotherapy and has added value when used with radiotherapy. PMID- 21975738 TI - Graduated driver licensing for reducing motor vehicle crashes among young drivers. AB - BACKGROUND: Graduated driver licensing (GDL) has been proposed as a means of reducing crash rates among novice drivers by gradually introducing them to higher risk driving situations. OBJECTIVES: To examine the effectiveness of GDL in reducing crash rates among young drivers. SEARCH STRATEGY: Studies were identified through searching MEDLINE, EMBASE, CINAHL, Healthstar, Web of Science, NTIS Bibliographic Database, TRIS Online, SIGLE, the World Wide Web, conference proceedings, consultation with experts and reference lists in relevant published literature. The searches were conducted from the time of inception to May 2009, and the Cochrane Injuries Group conducted an updated search of the TRANSPORT database in September 2009. SELECTION CRITERIA: Studies were included if: 1) they compared outcomes pre- and post-implementation of a GDL program within the same jurisdiction, 2) comparisons were made between jurisdictions with and without GDL, or 3) both. Studies had to report at least one objective, quantified outcome. DATA COLLECTION AND ANALYSIS: Results were not pooled due to substantial heterogeneity. Percentage change was calculated for each year after the intervention, using one year prior to the intervention as baseline. Results were adjusted by internal controls. Analyses were stratified by denominators (population, licensed drivers). Results were calculated for the different crash types and presented for 16 year-olds alone as well as all teenage drivers. MAIN RESULTS: We included 34 studies evaluating 21 GDL programs and 2 analyses of >40 US states. GDL programs were implemented in the US (n=16), Canada (n=3), New Zealand (n=1), and Australia (n=1) and varied in their restrictions during the intermediate stage. Based on the Insurance Institute for Highway Safety (IIHS) classification, eleven programs were good, four were fair, five were marginal, one was poor and two could not be assessed. Reductions in crash rates were seen in all jurisdictions and for all crash types. Among 16 year-old drivers, the median decrease in per population adjusted overall crash rates during the first year was 15.5% (range -27 to -8%, five studies). There was a decrease in per population adjusted injury crash rates (median -21%, range -46 to -2%, five studies). Results for all teenage drivers, rates per licensed driver, and rates adjusting for internal controls were generally reduced when comparing within jurisdictions. AUTHORS' CONCLUSIONS: GDL is effective in reducing crash rates among young drivers, although the magnitude of the effect varies. The conclusions are supported by consistent findings, temporal relationship, and plausibility of the association. Stronger GDL programs (i.e. more restrictions or higher quality based on IIHS classification) appear to result in greater fatality reduction. Future studies should focus on which components and combination of components yield the greatest reductions. PMID- 21975739 TI - Impact of tobacco advertising and promotion on increasing adolescent smoking behaviours. AB - BACKGROUND: The tobacco industry denies that their marketing is targeted at young nonsmokers, but it seems more probable that tobacco advertising and promotion influences the attitudes of nonsmoking adolescents, and makes them more likely to try smoking. OBJECTIVES: To assess the effects of tobacco advertising and promotion on nonsmoking adolescents' future smoking behaviour. SEARCH STRATEGY: We searched the Cochrane Tobacco Group specialized register, the Cochrane Central Register of Controlled Trials, MEDLINE, the Cochrane Library, Sociological Abstracts, PsycLIT, ERIC, WorldCat, Dissertation Abstracts, ABI Inform and Current Contents to August 2011. SELECTION CRITERIA: We selected longitudinal studies that assessed individuals' smoking behaviour and exposure to advertising, receptivity or attitudes to tobacco advertising, or brand awareness at baseline, and assessed smoking behaviour at follow ups. Participants were adolescents aged 18 or younger who were not regular smokers at baseline. DATA COLLECTION AND ANALYSIS: Studies were prescreened for relevance by one reviewer. Two reviewers independently assessed relevant studies for inclusion. Data were extracted by one reviewer and checked by a second. MAIN RESULTS: Nineteen longitudinal studies that followed up a total of over 29,000 baseline nonsmokers met inclusion criteria. The studies measured exposure or receptivity to advertising and promotion in a variety of ways, including having a favourite advertisement or an index of receptivity based on awareness of advertising and ownership of a promotional item. One study measured the number of tobacco advertisements in magazines read by participants. All studies assessed smoking behaviour change in participants who reported not smoking at baseline. In 18 of the 19 studies the nonsmoking adolescents who were more aware of tobacco advertising or receptive to it, were more likely to have experimented with cigarettes or become smokers at follow up. There was variation in the strength of association, and the degree to which potential confounders were controlled for. AUTHORS' CONCLUSIONS: Longitudinal studies consistently suggest that exposure to tobacco advertising and promotion is associated with the likelihood that adolescents will start to smoke. Based on the strength and specificity of this association, evidence of a dose-response relationship, the consistency of findings across numerous observational studies, temporality of exposure and smoking behaviours observed, as well as the theoretical plausibility regarding the impact of advertising, we conclude that tobacco advertising and promotion increases the likelihood that adolescents will start to smoke. PMID- 21975740 TI - Oral immunoglobulin for the treatment of rotavirus diarrhea in low birth weight infants. AB - BACKGROUND: Rotavirus infection is the most common neonatal nosocomial viral infection. It is a major health problem worldwide. Epidemics with the newer P(6)G9 strains have been reported in neonatal units globally. These strains can cause severe symptoms in most infected infants. Infection control measures become necessary and the utilization of hospital resources increase. Local mucosal immunity in the intestine to rotavirus is important in the resolution of infection and protection against subsequent infections. Boosting local immunity by oral administration of anti-rotaviral immunoglobulin preparations might be a useful strategy in treating rotaviral infections, especially in low birth weight babies. OBJECTIVES: To determine the effectiveness and safety of oral immunoglobulin preparations for the treatment of rotavirus diarrhea in hospitalized low birth weight infants (birth weight less than 2500 g) SEARCH STRATEGY: Electronic databases including The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2004), MEDLINE, EMBASE and CINAHL, Biological Abstracts (BIOSIS) were searched by the strategy outlined in the protocol. Science Citation Index search for all articles that referenced Barnes 1982 were searched. The proceedings of the Pediatric Academic Societies published online at 'Abstracts Online' were searched. Ongoing registered trials at www.clinicaltrials.gov and www.controlled-trials.com were searched. Authors prominent in the field were contacted for any unpublished articles and more information on published articles was sought. Reference lists of identified clinical trials and personal files were also reviewed. The above search was updated in July 2011. SELECTION CRITERIA: The criteria used to select studies for inclusion were: 1) DESIGN: randomized or quasi-randomized controlled trials 2) Hospitalized low birth weight infants with rotavirus diarrhea 3) INTERVENTION: Oral immunoglobulin preparations compared to placebo or no intervention 4) At least one of the following outcomes were reported: All cause mortality during hospital stay, mortality due to rotavirus infection during hospital stay, duration of diarrhea, need for rehydration, duration of viral excretion, duration of infection control measures, length of hospital stay in days, recurrent diarrhea or chronic diarrhea DATA COLLECTION AND ANALYSIS: The two reviewers were to independently abstract data from eligible trials. No data were available for analysis. MAIN RESULTS: No eligible randomized controlled trials were found. AUTHORS' CONCLUSIONS: No randomized controlled trials that assessed the effectiveness or safety of oral immunoglobulin preparations for the treatment of rotavirus diarrhea in hospitalized low birth weight infants were found. Clinical trials that address the issue of oral immunoglobulin treatment of rotavirus infection are needed. PMID- 21975741 TI - Granulocyte transfusions for neonates with confirmed or suspected sepsis and neutropenia. AB - BACKGROUND: Neonates have immature granulopoiesis, which frequently results in neutropenia after sepsis. Neutropaenic septic neonates have a higher mortality than non-neutropenic septic neonates. Therefore, granulocyte transfusion to septic neutropenic neonates may improve outcomes. OBJECTIVES: The primary objective was to determine the effect of granulocyte or buffy coat transfusions as adjuncts to antibiotics, after confirmed or suspected sepsis in neutropenic neonates, on all-cause mortality during hospital stay and neurological outcome at >= year of age. Secondary objectives were to determine the effects of granulocyte transfusions on length of hospital stay in survivors to discharge, adverse effects and immunologic outcomes at >= year of age. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE, EMBASE and CINAHL, proceedings of the PAS conferences and ongoing trials at clinicaltrials.gov and clinical-trials.com were searched in July 2011. SELECTION CRITERIA: Studies where neutropenic neonates with suspected or confirmed sepsis were randomised or quasi-randomised to granulocyte or buffy coat transfusions at any dose or duration, and reporting any outcome of interest were included. DATA COLLECTION AND ANALYSIS: Relative risk (RR) and risk difference (RD) with 95% confidence intervals using the fixed effects model were reported for dichotomous outcomes. Pre-specified subgroup analyses were performed. MAIN RESULTS: Four trials were eligible for inclusion. Forty-four infants with sepsis and neutropenia were randomised in three trials to granulocyte transfusions or placebo/no transfusion. In another trial, 35 infants with sepsis and neutropenia on antibiotics were randomised to granulocyte transfusion or IVIG.When granulocyte transfusion was compared with placebo or no transfusion, there was no significant difference in 'all-cause mortality' (three trials; typical RR 0.89, 95% CI 0.43 to 1.86; typical RD -0.05, 95% CI -0.31 to 0.21).When granulocyte transfusion was compared with intravenous immunoglobulin (one trial), there was a reduction in 'all-cause mortality' of borderline statistical significance (RR 0.06, 95% CI 0.00 to 1.04; RD -0.34, 95% CI -0.60 to -0.09; NNT 2.7, 95% CI 1.6 to 9.1).Pulmonary complications were the only adverse effect reported in the trials that used buffy coat transfusions. None of the trials reported on neurological outcome at one year of age or later, length of hospital stay in survivors to discharge or immunological outcome at one year of age or later. AUTHORS' CONCLUSIONS: Currently, there is inconclusive evidence from randomised controlled trials (RCTs) to support or refute the routine use of granulocyte transfusions in neutropenic, septic neonates. Researchers are encouraged to conduct adequately powered multi-centre trials of granulocyte transfusions in neutropenic septic neonates. PMID- 21975742 TI - Psychosocial combined with agonist maintenance treatments versus agonist maintenance treatments alone for treatment of opioid dependence. AB - BACKGROUND: Maintenance treatments are effective in retaining patients in treatment and suppressing heroin use. Questions remain regarding the efficacy of additional psychosocial services. OBJECTIVES: To evaluate the effectiveness of any psychosocial plus any agonist maintenance treatment versus standard agonist treatment for opiate dependence SEARCH STRATEGY: We searched the Cochrane Drugs and Alcohol Group trials register (June 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 6, 2011), PUBMED (1996 to 2011); EMBASE (January 1980 to 2011); CINAHL (January 2003 to 2011); PsycINFO (1985 to 2003) and reference list of articles. SELECTION CRITERIA: Randomised controlled trials and controlled clinical trial comparing any psychosocial plus any agonist with any agonist alone for opiate dependence. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality quality and extracted data. MAIN RESULTS: 35 studies, 4319 participants, were included. These studies considered thirteen different psychosocial interventions. Comparing any psychosocial plus any maintenance pharmacological treatment to standard maintenance treatment, results do not show benefit for retention in treatment, 27 studies, 3124 participants, RR 1.03 (95% CI 0.98 to 1.07), abstinence by opiate during the treatment, 8 studies, 1002 participants, RR 1.12 (95% CI 0.92 to 1.37), compliance, three studies, MD 0.43 (95% CI -0.05 to 0.92), psychiatric symptoms, 3 studies, MD 0.02 (-0.28 to 0.31), depression, 3 studies, MD -1.70 (95% CI -3.91 to 0.51) and results at the end of follow up as number of participants still in treatment, 3 studies, 250 participants, RR 0.90 (95% CI 0.77 to 1.07) and participants abstinent by opioid, 3 studies, 181 participants, RR 1.15 (95% CI 0.98 to 1.36). Comparing the different psychosocial approaches, results are never statistically significant for all the comparisons and outcomes. AUTHORS' CONCLUSIONS: For the considered outcomes, it seems that adding any psychosocial support to standard maintenance treatments do not add additional benefits. Data do not show differences also for contingency approaches, contrary to all expectations. Duration of the studies was too short to analyse relevant outcomes such as mortality. It should be noted that the control intervention used in the studies included in the review on maintenance treatments, is a program that routinely offers counselling sessions in addition to methadone; thus the review, actually, did not evaluate the question of whether any ancillary psychosocial intervention is needed when methadone maintenance is provided, but the narrower question of whether a specific more structured intervention provides any additional benefit to a standard psychosocial support. These interventions probably can be measured and evaluated by employing diverse criteria for evaluating treatment outcomes, aimed to rigorously assess changes in emotional, interpersonal, vocational and physical health areas of life functioning. PMID- 21975743 TI - Evening versus morning dosing regimen drug therapy for hypertension. AB - BACKGROUND: Variation in blood pressure levels display circadian rhythms. The morning surge in blood pressure is known to increase the risk of myocardial events in the first several hours post awakening. A systematic review of the administration-time-related-effects of evening versus morning dosing regimen of antihypertensive drugs in the management of patients with primary hypertension has not been conducted. OBJECTIVES: To evaluate the administration-time-related effects of antihypertensive drugs administered as once daily monotherapy in the evening versus morning administration regimen on all cause mortality, cardiovascular morbidity and reduction of blood pressure in patients with primary hypertension. SEARCH STRATEGY: We searched Cochrane CENTRAL on Ovid (4th Quarter 2009), Ovid MEDLINE (1950 to October 2009), EMBASE (1974 to October 2009), the Chinese Biomedical literature database (1978 to 2009) and the reference lists of relevant articles. No language restrictions were applied. SELECTION CRITERIA: Randomized controlled trials comparing the administration-time-related effects of evening with morning dosing monotherapy regimens in patients with primary hypertension were included. Patients with known secondary hypertension, shift workers or white coat hypertension were excluded. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed trial quality. Disagreements were resolved by discussion or a third reviewer. Data synthesis and analysis were done using RevMan 5.1. Random effects meta-analysis and sensitivity analysis were conducted. MAIN RESULTS: 21 randomized controlled trials (RCTs) in 1,993 patients with primary hypertension met the inclusion criteria for this review - ACEIs (5 trials), CCBs (7 trials), ARBs (6 trials), diuretics (2 trials), alpha-blockers (1 trial), and beta-blockers (1 trial). Meta-analysis showed significant heterogeneity across trials.No RCT reported on all cause mortality, cardiovascular mortality, cardiovascular morbidity and serious adverse events.There was no statistically significant difference for overall adverse events (RR=0.78, 95%CI: 0.37 to 1.65) and withdrawals due to adverse events (RR=0.53, 95%CI: 0.26 to 1.07).No significant differences were noted for morning SBP (-1.62 mm Hg, 95% CI: -4.19 to 0.95) and morning DBP (-1.21 mm Hg, 95% CI: 3.28 to 0.86); but 24-hour BP (SBP: -1.71 mm Hg, 95% CI: -2.78 to -0.65; DBP: 1.38 mm Hg, 95% CI: -2.13 to -0.62) showed a statistically significant difference. AUTHORS' CONCLUSIONS: No RCT reported on clinically relevant outcome measures - all cause mortality, cardiovascular morbidity and morbidity. There were no significant differences in overall adverse events and withdrawals due to adverse events among the evening versus morning dosing regimens. In terms of BP lowering efficacy, for 24-hour SBP and DBP, the data suggests that better blood pressure control was achieved with bedtime dosing than morning administration of antihypertensive medication, the clinical significance of which is not known. PMID- 21975744 TI - Drugs and pacemakers for vasovagal, carotid sinus and situational syncope. AB - BACKGROUND: Neurally mediated reflex syncope is the most common cause of transient loss of consciousness. In patients not responding to non pharmacological treatment, pharmacological or pacemaker treatment might be considered. OBJECTIVES: To examine the effects of pharmacological therapy and pacemaker implantation in patients with vasovagal syncope, carotid sinus syncope and situational syncope. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 1, 2008), PubMed (1950 until February 2008), EMBASE on OVID (1980 until February 2008) and CINAHL on EBSCOhost (1937 until February 2008). No language restrictions were applied. SELECTION CRITERIA: We included parallel randomized controlled trials and randomized cross-over trials of pharmacological treatment (beta-blockers, fludrocortisone, alpha-adrenergic agonists, selective serotonine reuptake inhibitors, ACE inhibitors, disopyramide, anticholinergic agents or salt tablets) or dual chamber pacemaker treatment. Studies were included if pharmacological or pacemaker treatment was compared with any form of standardised control treatment (standard treatment), placebo treatment, or (other) pharmacological or pacemaker treatment. We did not include non-randomized studies. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the risk of bias. Using a standardised data extraction form, they extracted characteristics and results of the various studies. In a consensus meeting they discussed any disagreements that had occurred during data extraction. If no agreement could be reached, a third reviewer was asked to make a decision. Summary estimates with 95% confidence intervals of treatment effect were calculated using relative risks, rate ratios or weighted means differences depending on the type of outcome reported. MAIN RESULTS: We included 46 randomized studies, 40 on vasovagal syncope and six on carotid sinus syncope. No studies on situational syncope matched the criteria for inclusion in our review. Studies in general were small with a median sample size of 42. A wide range of control treatments were used with 22 studies using a placebo arm. Blinding of patients and treating physicians was applied in eight studies. Results varied considerably between studies and between types of outcomes.For vasovagal syncope, the occurrence of syncope upon provocational head up tilt testing was lower upon treatment with beta-blockers, ACE-inhibitors and anticholinergic agents compared to standard treatment. For carotid sinus syncope, the occurrence of syncope upon carotid sinus massage was lower on midodrine treatment compared to placebo treatment in one study. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the use of any of the pharmacological or pacemaker treatments for vasovagal syncope and carotid sinus syncope. Larger studies using patient relevant outcomes are needed. PMID- 21975745 TI - Pentoxifylline for treatment of sepsis and necrotizing enterocolitis in neonates. AB - BACKGROUND: Mortality and morbidity due to neonatal sepsis and necrotizing enterocolitis (NEC) is high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline, a phosphodiesterase inhibitor, is one such agent. OBJECTIVES: The primary objectives were to assess the effect on mortality and the safety of intravenous pentoxifylline as an adjunct to antibiotic therapy in neonates with suspected or confirmed sepsis and NEC. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2011), MEDLINE, EMBASE and CINAHL, Science Citation Index for articles referencing Lauterbach 1996, proceedings of the Pediatric Academic Societies (1990 to 2011), BIOSIS (1992 to 2011), conference proceedings (1992 to 2011), ongoing trials and reference lists of identified RCTs were searched in July 2011. SELECTION CRITERIA: Randomised or quasi-randomised trials assessing the efficacy of pentoxifylline as an adjunct to antibiotics for treatment of suspected or confirmed sepsis or NEC in neonates were eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted information for the outcomes of interest. Typical relative risk (RR) and risk difference (RD) with 95% confidence intervals (CI) using fixed effects model are reported for dichotomous outcomes and mean differences for continuous outcomes. NNT was calculated for outcomes for which there was a statistically significant reduction in RD. MAIN RESULTS: In four randomised controlled trials, 227 neonates with suspected or confirmed sepsis were randomised to pentoxifylline or placebo. Pentoxifylline therapy significantly decreased "all cause mortality during hospital stay" in the overall population of infants with sepsis [typical RR 0.40 (95%CI 0.20 to 0.77); typical RD -0.15 (95%CI -0.26 to -0.05); NNT 7 (95%CI 4 to 20)]. Subgroup analyses revealed significant reduction in mortality in preterm infants, infants with confirmed sepsis and gram-negative sepsis. Pentoxifylline treatment significantly decreased length of hospital stay [mean difference -11.20 [95%CI -22.09 to -0.31] but not development of NEC in neonates with sepsis [typical RR 0.29 (95%CI 0.07 to 1.24); typical RD -0.20 (95%CI -0.41 to 0.01)]. No adverse effects due to pentoxifylline were noted. No completed trial of treatment with pentoxifylline for treatment of NEC was identified. AUTHORS' CONCLUSIONS: Current evidence from four small studies suggests that the use of pentoxifylline as an adjunct to antibiotics in neonatal sepsis decreases mortality without any adverse effects. Researchers are encouraged to undertake large well-designed multicenter trials to confirm or refute the effectiveness of pentoxifylline in reducing mortality and adverse outcomes in neonates with suspected or confirmed neonatal sepsis and NEC. PMID- 21975746 TI - Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever). AB - BACKGROUND: Typhoid and paratyphoid are febrile illnesses, due to a bacterial infection, which remain common in many low- and middle-income countries. The World Health Organization (WHO) currently recommends the fluoroquinolone antibiotics in areas with known resistance to the older first-line antibiotics. OBJECTIVES: To evaluate fluoroquinolone antibiotics for treating children and adults with enteric fever. SEARCH STRATEGY: We searched The Cochrane Infectious Disease Group Specialized Register (February 2011); Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library (2011, Issue 2); MEDLINE (1966 to February 2011); EMBASE (1974 to February 2011); and LILACS (1982 to February 2011). We also searched the metaRegister of Controlled Trials (mRCT) in February 2011. SELECTION CRITERIA: Randomized controlled trials examining fluoroquinolone antibiotics, in people with blood, stool or bone marrow culture confirmed enteric fever. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the trial's methodological quality and extracted data. We calculated risk ratios (RR) for dichotomous data and mean difference for continuous data with 95% confidence intervals (CI).Comparative effectiveness has been interpreted in the context of; length of treatment, dose, year of study, known levels of antibiotic resistance, or proxy measures of resistance such as the failure rate in the comparator arm. MAIN RESULTS: Twenty-six studies, involving 3033 patients, are included in this review.Fluoroquinolones versus older antibiotics (chloramphenicol, co-trimoxazole, amoxicillin and ampicillin)In one study from Pakistan in 2003-04, high clinical failure rates were seen with both chloramphenicol and co-trimoxazole, although resistance was not confirmed microbiologically. A seven-day course of either ciprofloxacin or ofloxacin were found to be superior. Older studies of these comparisons failed to show a difference (six trials, 361 participants).In small studies conducted almost two decades ago, the fluoroquinolones were demonstrated to have fewer clinical failures than ampicillin and amoxicillin (two trials, 90 participants, RR 0.11, 95% CI 0.02 to 0.57).Fluoroquinolones versus current second-line options (ceftriaxone, cefalexin, and azithromycin)The two studies comparing a seven day course of oral fluoroquinolones with three days of intravenous ceftriaxone were too small to detect important differences between antibiotics should they exist (two trials, 89 participants).In Pakistan in 2003-04, no clinical or microbiological failures were seen with seven days of either ciprofloxacin, ofloxacin or cefixime (one trial, 139 participants). In Nepal in 2005, gatifloxacin reduced clinical failure and relapse compared to cefixime, despite a high prevalence of NaR in the study population (one trial, 158 participants, RR 0.04, 95% CI 0.01 to 0.31).Compared to a seven day course of azithromycin, a seven day course of ofloxacin had a higher rate of clinical failures in populations with both multi-drug resistance (MDR) and nalidixic acid resistance (NaR) enteric fever in Vietnam in 1998-2002 (two trials, 213 participants, RR 2.20, 95% CI 1.23 to 3.94). However, a more recent study from Vietnam in 2004-05, detected no difference between gatifloxacin and azithromycin with both drugs performing well (one trial, 287 participants). AUTHORS' CONCLUSIONS: Generally, fluoroquinolones performed well in treating typhoid, and maybe superior to alternatives in some settings. However, we were unable to draw firm general conclusions on comparative contemporary effectiveness given that resistance changes over time, and many studies were small. Policy makers and clinicians need to consider local resistance patterns in choosing a fluoroquinolone or alternative.There is some evidence that the newest fluoroquinolone, gatifloxacin, remains effective in some regions where resistance to older fluoroquinolones has developed. However, the different fluoroquinolones have not been compared directly in trials in these settings. PMID- 21975747 TI - Treatment for anemia in people with AIDS. AB - BACKGROUND: Anemia is common in persons with HIV infection and is associated with poor prognosis. There is a need to assess the effects of anemia treatments, and to determine whether these interventions are beneficial. OBJECTIVES: To determine the efficacy and safety of treatments for anemia in people with HIV infection and AIDS. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 10, 2010), MEDLINE (1980-November 25, 2010), EMBASE (1980 November 25, 2010), LlLACS (1982 to November 25, 2010), Africa Index Medicus (up to November 9, 2010), ISI Web of Knowledge (2005 to October 9, 2010), Scirus (October 9, 2010) reference lists of relevant articles. We asked the Cochrane HIV/AIDS and Pregnancy and Childbirth Groups to check their Specialised Registers. We also checked the reference lists of all trials identified by the above methods. SELECTION CRITERIA: Randomized trials assessing the effects of treatments for anemia in people diagnosed with HIV infection. There were no age restrictions. DATA COLLECTION AND ANALYSIS: Two authors independently assessed relevant studies for inclusion. Data extraction and quality assessment of relevant studies was performed by two authors and checked by the other two authors. MAIN RESULTS: Six trials with a high risk of bias, including 537 patients, met the inclusion criteria. These trials only covered recombinant Human erythropoietin alfa (rHuEPO). Two of them including adult and paediatric participants (84 participants and 4 events) comparing rHuEPO to placebo did not reduce the risk of mortality with a follow up to 12 weeks (pooled RR 0.56, 95% confidence interval (CI) 0.08 to 4.05, I(2) = 0%). Any trials that compared rHuEPO to placebo did not show any benefit on hematological values response, number of patients transfused, or number of packed red cell transfused. Two trial compared the effects of two rHuEPO dosing regimens on hemoglobin value and quality of life, but the effects are unclear. Three RCT reported high risk of attrition bias; therefore, were not included in a meta-analysis. AUTHORS' CONCLUSIONS: This updated Cochrane review provides evidence that rHuEPO compared with placebo does not reduce mortality, does not reduce transfusion requirements, did not increase hemoglobin levels, and did not improve quality of life in HIV infected patients with anemia. The results are based on six RCTs with high risk of bias. Therefore prescription of this intervention for treating anemia in patients with AIDS is not justified, unless new evidence from a large high quality trial alters this conclusion. PMID- 21975748 TI - Thiazide diuretics and the risk of hip fracture. AB - BACKGROUND: Thiazide diuretics are one of the most commonly prescribed antihypertensive agents worldwide. Thiazides reduce urinary calcium excretion. Chronic ingestion of thiazides is associated with higher bone mineral density. It has been suggested that thiazides may prevent hip fracture. However, there are concerns that diuretics, by increasing the risk of fall in elderly, could potentially negate its beneficial effects on hip fracture. OBJECTIVES: To assess any association between the use of thiazide diuretics and the risk of hip fracture in adults. SEARCH STRATEGY: We searched eligible studies up to December 2008 in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), International Pharmaceutical Abstracts, the Database of Abstracts of Review of Effects (DARE) and reference lists of previous reviews and included studies. SELECTION CRITERIA: All randomized controlled trials and observational studies, which assessed the association between thiazide diuretic use and hip fracture. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the selection criteria, extracted data and assessed risk of bias of each study selected. The results were summarized descriptively and quantitatively. Cohort studies and case control studies were analysed separately. MAIN RESULTS: No randomized control trials were found. Twenty-one observational studies with nearly four hundred thousand participants were included. Six of them were cohort studies and 15 were case-control studies. Two cohort studies appear to involve the same cohort so there were only 5 unique ones. The risk of bias was assessed with the Newcastle-Ottawa Scale (NOS). Five cohort studies had low risk of bias and one had moderate risk of bias. Seven case control studies had low risk of bias and 8 had moderate risk of bias. Meta-analysis of cohort studies showed that thiazide use was associated with a reduction in risk of hip fracture by 24%, pooled RR 0.76 (95% CI 0.64-0.89; p = 0.0009). We chose not to provide a pooled summary statistics for case-control studies because of high heterogeneity (Tau(2) = 0.03, I(2) = 62%, p = 0.0008). AUTHORS' CONCLUSIONS: Thiazides appear to reduce the risk of hip fracture based on observational studies. Randomized controlled trials are needed to confirm these findings. PMID- 21975749 TI - Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease. AB - BACKGROUND: Pulmonary rehabilitation has become a cornerstone in the management of patients with stable Chronic Obstructive Pulmonary Disease (COPD). Systematic reviews have shown large and important clinical effects of pulmonary rehabilitation in these patients. However, in unstable COPD patients who have recently suffered an exacerbation, the effects of pulmonary rehabilitation are less established. OBJECTIVES: To assess the effects of pulmonary rehabilitation after COPD exacerbations on future hospital admissions (primary outcome) and other patient-important outcomes (mortality, health-related quality of life and exercise capacity). SEARCH STRATEGY: Trials were identified from searches of CENTRAL, MEDLINE, EMBASE, PEDRO and the Cochrane Airways Group Register of Trials. Searches were current as of March 2010. SELECTION CRITERIA: Randomized controlled trials comparing pulmonary rehabilitation of any duration after exacerbation of COPD with conventional care. Pulmonary rehabilitation programmes needed to include at least physical exercise. Control groups received conventional community care without rehabilitation. DATA COLLECTION AND ANALYSIS: We calculated pooled odds ratios and weighted mean differences (MD) using random effects models. We requested missing data from the authors of the primary studies. MAIN RESULTS: We identified nine trials involving 432 patients. Pulmonary rehabilitation significantly reduced hospital admissions (pooled odds ratio 0.22 [95% CI 0.08 to 0.58], number needed to treat (NNT) 4 [95% CI 3 to 8], over 25 weeks) and mortality (OR 0.28; 95% CI 0.10 to 0.84), NNT 6 [95% CI 5 to 30] over 107 weeks). Effects of pulmonary rehabilitation on health-related quality of life were well above the minimal important difference when measured by the Chronic Respiratory Questionnaire (MD for dyspnea, fatigue, emotional function and mastery domains between 0.81 (fatigue; 95% CI 0.16 to 1.45) and 0.97 (dyspnea; 95% CI 0.35 to 1.58)) and the St. Georges Respiratory Questionnaire total score (MD -9.88; 95% CI -14.40 to -5.37); impacts domain (MD -13.94; 95% CI -20.37 to -7.51) and for activity limitation domain (MD -9.94; 95% CI -15.98 to 3.89)). The symptoms domain of the St. Georges Respiratory Questionnaire showed no significant improvement. Pulmonary rehabilitation significantly improved exercise capacity and the improvement was above the minimally important difference (six-minute walk test (MD 77.70 meters; 95% CI 12.21 to 143.20) and shuttle walk test (MD 64.35; 95% CI 41.28 to 87.43)). No adverse events were reported in three studies. AUTHORS' CONCLUSIONS: Evidence from nine small studies of moderate methodological quality, suggests that pulmonary rehabilitation is a highly effective and safe intervention to reduce hospital admissions and mortality and to improve health-related quality of life in COPD patients who have recently suffered an exacerbation of COPD. PMID- 21975750 TI - Endovenous ablation (radiofrequency and laser) and foam sclerotherapy versus conventional surgery for great saphenous vein varices. AB - BACKGROUND: Minimally invasive techniques to treat great saphenous varicose veins include ultrasound-guided foam sclerotherapy (USGFS), radiofrequency ablation (RFA) and endovenous laser therapy (EVLT). Compared with conventional surgery (high ligation and stripping (HL/S)), proposed benefits include fewer complications, quicker return to work, improved quality of life (QoL) scores, reduced need for general anaesthesia and equivalent recurrence rates. OBJECTIVES: To review available randomised controlled clinical trials (RCT) data comparing USGFS, RFA, EVLT to HL/S for the treatment of great saphenous varicose veins. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases (PVD) Group searched their Specialised Register (July 2010) and CENTRAL (The Cochrane Library 2010, Issue 3). In addition the authors performed a search of EMBASE (July 2010). Manufacturers of EVLT, RFA and sclerosant equipment were contacted for trial data. SELECTION CRITERIA: All RCTs of EVLT, RFA, USGFS and HL/S were considered for inclusion. Primary outcomes were recurrent varicosities, recanalisation, neovascularisation, technical procedure failure or need for re-intervention, patient quality of life (QoL) scores and associated complications. Secondary outcomes were type of anaesthetic, procedure duration, hospital stay and cost. DATA COLLECTION AND ANALYSIS: CN, RE, VB, PC, HB and GS independently reviewed, assessed and selected trials which met the inclusion criteria. CN and RE extracted data. The Cochrane Collaboration's tool for assessing risk of bias was used. CN contacted trial authors to clarify details. MAIN RESULTS: Thirteen reports from five studies with a combined total of 450 patients were included. Rates of recanalisation were higher following EVLT compared with HL/S, both early (within four months) (5/149 versus 0/100; odds ratio (OR) 3.83, 95% confidence interval (CI) 0.45 to 32.64) and late recanalisation (after four months) (9/118 versus 1/80; OR 2.97 95% CI 0.52 to 16.98), although these results were not statistically significant. Technical failure rates favoured EVLT over HL/S (1/149 versus 6/100; OR 0.12, 95% CI 0.02 to 0.75). Recurrence following RFA showed no difference when compared with surgery. Recanalisation within four months was observed more frequently following RFA compared with HL/S although not statistically significant (4/105 versus 0/88; OR 7.86, 95% CI 0.41 to 151.28); after four months no difference was observed. Neovascularisation was observed more frequently following HL/S compared with RFA, but again this was not statistically significant (3/42 versus 8/51; OR 0.39, 95% CI 0.09 to 1.63). Technical failure was observed less frequently following RFA compared with HL/S although this was not statistically significant (2/106 versus 7/96; OR 0.48, 95% CI 0.01 to 34.25). No randomised clinical trials comparing HL/S versus USGFS met our study inclusion criteria. QoL scores and operative complications were not amenable to meta-analysis. AUTHORS' CONCLUSIONS: Currently available clinical trial evidence suggests RFA and EVLT are at least as effective as surgery in the treatment of great saphenous varicose veins. There are insufficient data to comment on USGFS. Further randomised trials are needed. We should aim to report and analyse results in a congruent manner to facilitate future meta-analysis. PMID- 21975751 TI - WITHDRAWN: Azithromycin for treating uncomplicated typhoid and paratyphoid fever (enteric fever). AB - BACKGROUND: Review status: Current question - no update intended. Azithromycin treatments are included in the review: Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever). (Thaver D, Zaidi AKM, Critchley JA, Azmatullah A, Madni SA, Bhutta ZA. Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever). Cochrane Database of Systematic Reviews 2008, Issue 4. Art. No.: CD004530. DOI: 10.1002/14651858.CD004530.pub3.) This latter review is being updated, and will be published in late 2011.Enteric fever (typhoid and paratyphoid fever) is potentially fatal. Infection with drug-resistant strains of the causative organism Salmonella enterica serovar Typhi or Paratyphi increases morbidity and mortality. Azithromycin may have better outcomes in people with uncomplicated forms of the disease. OBJECTIVES: To compare azithromycin with other antibiotics for treating uncomplicated enteric fever. SEARCH STRATEGY: In August 2008, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2008, Issue 3), MEDLINE, EMBASE, LILACS, and mRCT. We also searched conference proceedings, reference lists, and contacted researchers and a pharmaceutical company. SELECTION CRITERIA: Randomized controlled trials comparing azithromycin with other antibiotics for treating children and adults with uncomplicated enteric fever confirmed by cultures of S. Typhi or Paratyphi in blood and/or stool. DATA COLLECTION AND ANALYSIS: Both authors independently extracted data and assessed the risk of bias. Dichotomous data were presented and compared using the odds ratio, and continuous data were reported as arithmetic means with standard deviations and were combined using the mean difference (MD). Both were presented with 95% confidence intervals (CI). MAIN RESULTS: Seven trials involving 773 participants met the inclusion criteria. The trials used adequate methods to generate the allocation sequence and conceal allocation, and were open label. Three trials exclusively included adults, two included children, and two included both adults and children; all were hospital inpatients. One trial evaluated azithromycin against chloramphenicol and did not demonstrate a difference for any outcome (77 participants, 1 trial). When compared with fluoroquinolones in four trials, azithromycin significantly reduced clinical failure (OR 0.48, 95% CI 0.26 to 0.89; 564 participants, 4 trials) and duration of hospital stay (MD -1.04 days, 95% CI -1.73 to -0.34 days; 213 participants, 2 trials); all four trials included people with multiple-drug resistant or nalidixic acid-resistant strains of S. Typhi or S. Paratyphi. We detected no statistically significant difference in the other outcomes. Compared with ceftriaxone, azithromycin significantly reduced relapse (OR 0.09, 95% CI 0.01 to 0.70; 132 participants, 2 trials) and not other outcome measures. Few adverse events were reported, and most were mild and self limiting. AUTHORS' CONCLUSIONS: Azithromycin appears better than fluoroquinolone drugs in populations that included participants with drug-resistant strains. Azithromycin may perform better than ceftriaxone. PMID- 21975752 TI - Non-pharmacological management of infant and young child procedural pain. AB - BACKGROUND: Infant acute pain and distress is commonplace. Infancy is a period of exponential development. Unrelieved pain and distress can have implications across the lifespan. OBJECTIVES: To assess the efficacy of non-pharmacological interventions for infant and child (up to three years) acute pain, excluding breastmilk, sucrose, and music. Analyses accounted for infant age (preterm, neonate, older) and pain response (pain reactivity, pain-related regulation). SEARCH STRATEGY: We searched CENTRAL in The Cochrane Library (2011, Issue 1), MEDLINE (1966 to April 2011), EMBASE (1980 to April 2011), PsycINFO (1967 to April 2011), Cumulative Index to Nursing and Allied Health Literature (1982 to 2011), Dissertation Abstracts International (1980 to 2011) and www.clinicaltrials.gov. We also searched reference lists and contacted researchers via electronic list-serves. SELECTION CRITERIA: Participants included infants from birth to three years. Only randomized controlled trials (RCTs) or RCT cross-overs that had a no-treatment control comparison were eligible for inclusion in the analyses. We examined studies that met all inclusion criteria except for study design (e.g. had an active control) to qualitatively contextualize results. DATA COLLECTION AND ANALYSIS: We refined search strategies with three Cochrane-affiliated librarians. At least two review authors extracted and rated 51 articles. Study quality ratings were based on a scale by Yates and colleagues. We analyzed the standardized mean difference (SMD) using the generic inverse variance method. We also provided qualitative descriptions of 20 relevant but excluded studies. MAIN RESULTS: Fifty-one studies, with 3396 participants, were analyzed. The most commonly studied acute procedures were heel-sticks (29 studies) and needles (n = 10 studies). The largest SMD for treatment improvement over control conditions on pain reactivity were: non-nutritive sucking-related interventions (preterm: SMD -0.42; 95% CI -0.68 to -0.15; neonate: SMD -1.45, 95% CI -2.34 to -0.57), kangaroo care (preterm: SMD -1.12, 95% CI -2.04 to -0.21), and swaddling/facilitated tucking (preterm: SMD -0.97; 95% CI -1.63 to -0.31). For immediate pain-related regulation, the largest SMDs were: non-nutritive sucking-related interventions (preterm: SMD -0.38; 95% CI -0.59 to -0.17; neonate: SMD -0.90, 95% CI -1.54 to -0.25), kangaroo care (SMD -0.77, 95% CI 1.50 to -0.03), swaddling/facilitated tucking (preterm: SMD -0.75; 95% CI -1.14 to -0.36), and rocking/holding (neonate: SMD -0.75; 95% CI -1.20 to -0.30). The presence of significant heterogeneity limited our confidence in the lack of findings for certain analyses. AUTHORS' CONCLUSIONS: There is evidence that different non-pharmacological interventions can be used with preterms, neonates, and older infants to significantly manage pain behaviors associated with acutely painful procedures. PMID- 21975753 TI - Glucagon-like peptide analogues for type 2 diabetes mellitus. AB - BACKGROUND: Glucagon-like peptide analogues are a new class of drugs used in the treatment of type 2 diabetes that mimic the endogenous hormone glucagon-like peptide 1 (GLP-1). GLP-1 is an incretin, a gastrointestinal hormone that is released into the circulation in response to ingested nutrients. GLP-1 regulates glucose levels by stimulating glucose-dependent insulin secretion and biosynthesis, and by suppressing glucagon secretion, delayed gastric emptying and promoting satiety. OBJECTIVES: To assess the effects of glucagon-like peptide analogues in patients with type 2 diabetes mellitus. SEARCH STRATEGY: Studies were obtained from electronic searches of The Cochrane Library (last search issue 1, 2011), MEDLINE (last search March 2011), EMBASE (last search March 2011), Web of Science (last search March 2011) and databases of ongoing trials. SELECTION CRITERIA: Studies were included if they were randomised controlled trials of a minimum duration of eight weeks comparing a GLP-1 analogue with placebo, insulin, an oral anti-diabetic agent, or another GLP-1 analogue in people with type 2 diabetes. DATA COLLECTION AND ANALYSIS: Data extraction and quality assessment of studies were done by one reviewer and checked by a second. Data were analysed by type of GLP-1 agonist and comparison treatment. Where appropriate, data were summarised in a meta-analysis (mean differences and risk ratios summarised using a random-effects model). MAIN RESULTS: Seventeen randomised controlled trials including relevant analyses for 6899 participants were included in the analysis. Studies were mostly of short duration, usually 26 weeks.In comparison with placebo, all GLP-1 agonists reduced glycosylated haemoglobin A1c (HbA1c) levels by about 1%. Exenatide 2 mg once weekly and liraglutide 1.8 mg reduced it by 0.20% and 0.24% respectively more than insulin glargine. Exenatide 2 mg once weekly reduced HbA1c more than exenatide 10 MUg twice daily, sitagliptin and pioglitazone. Liraglutide 1.8 mg reduced HbA1c by 0.33% more than exenatide 10 MUg twice daily. Liraglutide led to similar improvements in HbA1c compared to sulphonylureas but reduced it more than sitagliptin and rosiglitazone.Both exenatide and liraglutide led to greater weight loss than most active comparators, including in participants not experiencing nausea. Hypoglycaemia occurred more frequently in participants taking concomitant sulphonylurea. GLP-1 agonists caused gastrointestinal adverse effects, mainly nausea. These adverse events were strongest at the beginning and then subsided. Beta-cell function was improved with GLP-1 agonists but the effect did not persist after cessation of treatment.None of the studies was long enough to assess long-term positive or negative effects. AUTHORS' CONCLUSIONS: GLP-1 agonists are effective in improving glycaemic control. PMID- 21975754 TI - Oral iron supplements for children in malaria-endemic areas. AB - BACKGROUND: Iron-deficiency anaemia is common during childhood. Iron supplementation has been claimed to increase the risk of malaria. OBJECTIVES: To assess the effect of iron on malaria and deaths. SEARCH STRATEGY: We searched The Cochrane Library, PUBMED, MEDLINE, LILACS; and trial registry databases, all up to June 2011. We scanned references of included trials. SELECTION CRITERIA: Individually and cluster randomized controlled trials conducted in hypoendemic to holoendemic malaria regions and including children below 18 years of age. We included trials comparing orally administered iron, iron with antimalarial treatment, or iron with folic acid versus placebo or no treatment. Iron fortification was excluded. Antihelminthics could be administered to either group. Additional micronutrients had to be administered equally to both groups. DATA COLLECTION AND ANALYSIS: The primary outcomes were clinical (symptomatic) malaria, severe malaria, and death. Two authors independently selected the studies and extracted the data. We assessed heterogeneity and conducted subgroup analyses by the presence of anaemia at baseline, age, and malaria endemicity. We assessed risk of bias using domain-based evaluation. We performed a fixed-effect meta-analysis for all outcomes and random-effects meta-analysis for hematological outcomes. We adjusted analyses for cluster randomized trials. MAIN RESULTS: Seventy-one trials (45,353 children) were included. For clinical malaria, no significant difference between iron alone and placebo was detected, (risk ratio (RR) 0.99, 95% confidence intervals (CI) 0.90 to 1.09, 13 trials). The results were similar in the subgroups of non-anaemic children and children below 2 years of age. There was no significant difference in deaths in hyper- and holoendemic areas, risk difference +1.93 per 1000 children (95% CI -1.78 to 5.64, 13 trials, 17,898 children). Iron administered for treatment of anaemia resulted in a larger increase in haemoglobin than iron given for prevention, and the benefit was similar in hyper- or holoendemic and lower endemicity settings. Iron and folic acid supplementation resulted in mixed results for severe malaria. Overall, the risk for clinical malaria was higher with iron or with iron plus folic acid in trials where services did not provide for malaria surveillance and treatment. Iron with antimalarial treatment significantly reduced malaria. Iron supplementation during an acute attack of malaria did not increase the risk for parasitological failure, (RR 0.96, 95% CI 0.74 to 1.24, three trials) or deaths. AUTHORS' CONCLUSIONS: Iron alone or with antimalaria treatment does not increase the risk of clinical malaria or death when regular malaria surveillance and treatment services are provided. There is no need to screen for anaemia prior to iron supplementation. PMID- 21975755 TI - Cooling for cerebral protection during brain surgery. AB - BACKGROUND: The brain is at risk of ischaemia during a variety of neurosurgical procedures, and this can lead to devastating results. Induced hypothermia is the controlled lowering of core body temperature for therapeutic purposes. This remains the current practice during neurosurgery for the prevention or minimization of ischaemic brain injury. Brain surgery may lead to severe complications due to factors such as requirement for brain retraction, vessel occlusion, and intraoperative haemorrhage. Many anaesthesiologists believe that induced hypothermia is indicated to protect the central nervous system during surgery. Although hypothermia is often used during brain surgery, clinical efficacy has not yet been established. OBJECTIVES: To evaluate the effectiveness and safety of induced hypothermia versus normothermia for neuroprotection in patients undergoing brain surgery. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 10), MEDLINE, LILACS, EMBASE and Current Controlled Trials (from inception to November 2010), reference lists of identified trials, and bibliographies of published reviews. We also contacted researchers in the field. There were no language restrictions. SELECTION CRITERIA: We included randomized controlled trials and quasi-randomized controlled trials of induced hypothermia versus normothermia for neuroprotection in patients undergoing brain surgery. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. MAIN RESULTS: We included four trials of cooling for cerebral protection during brain surgery, involving a total of 1219 patients. We did not find any evidence that hypothermia for neuroprotection in patients undergoing brain surgery is either effective or unsafe when compared to normothermia. AUTHORS' CONCLUSIONS: Although there is some evidence that mild hypothermia is safe, its effectiveness is not clear when compared with normothermia. We need to perform more clinical trials in order to establish the benefit, if any, of hypothermia for cerebral protection during brain surgery before making firm recommendations for the routine use of this intervention. PMID- 21975756 TI - Intermittent preventive treatment regimens for malaria in HIV-positive pregnant women. AB - BACKGROUND: Intermittent preventive treatment is recommended for pregnant women living in malaria endemic countries due to benefits for both mother and baby. However, the impact may not be the same in HIV-positive pregnant women, as HIV infection impairs a woman's immunity. OBJECTIVES: To compare intermittent preventive treatment regimens for malaria in HIV-positive pregnant women living in malaria-endemic areas. SEARCH STRATEGY: In June 2011, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE; EMBASE; LILACS, the metaRegister of Controlled Trials (mRCT), reference lists and conference abstracts. We also contacted researchers and organizations for information on relevant trials. SELECTION CRITERIA: Randomized controlled trials comparing different intermittent preventive treatment regimens for preventing malaria in HIV-positive pregnant women in malaria-endemic areas. DATA COLLECTION AND ANALYSIS: Two authors extracted data and assessed risk bias. Dichotomous variables were combined using risk ratios (RR) and mean differences (MD) for continuous outcomes, both with 95% confidence intervals (CI). MAIN RESULTS: Two randomized trials with 722 HIV-positive pregnant women were included, comparing monthly regimens of sulfadoxine-pyrimethamine (SP) to the standard 2-dose regimen in the second and third trimesters. There were no statistically significant differences between monthly SP and 2-dose SP in rates of maternal anaemia, low birth weight, and neonatal mortality. In primigravidae and secondigravidiae, the monthly regimen was associated with less placental parasitaemia (RR 0.38, 95% CI 0.21 to 0.70, two trials) and less peripheral parasitaemia (RR 0.25, 95% CI 0.14 to 0.43, two trials), but no effect was demonstrated in multigravid women. Babies born to primigravidae and secundigravida women on monthly SP had a higher mean birth weight (weighted mean difference (WMD) 130 g; 95% CI 120 g to 150 g, two trials) than babies born to mothers on 2-dose SP. Multigravidae women treated with monthly SP had significant higher haemoglobin level than those treated with treated 2 dose SP (WMD 0.21 g/dL, 95% CI 0.15 g/dL to 0.27 g/dL, one trial). There were no trials that assessed other treatment regimens for intermittent preventive treatment in HIV-positive pregnant women. AUTHORS' CONCLUSIONS: Three or more doses of SP is superior to the standard two doses in HIV-positive pregnant women. However, since SP cannot be administered concurrently with co trimoxazole - a drug often recommended for infection prophylaxis in HIV-positive pregnant women, new drugs and research is needed to address needs of HIV-positive pregnant women. PMID- 21975757 TI - Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease. AB - BACKGROUND: Current guidelines recommend that acute exacerbations of chronic obstructive pulmonary disease (COPD) be treated with systemic corticosteroids (SCs) for seven to 14 days. Intermittent SC use is cumulatively associated with adverse effects such as osteoporosis, hyperglycaemia and muscle weakness. Shorter treatment could therefore reduce the risk of adverse effects. OBJECTIVES: To compare the efficacy of short-duration (seven days or fewer) and longer-duration (more than seven days) SC treatment of acute COPD exacerbations in adults. SEARCH STRATEGY: We searched the Cochrane Airways Group Register of Trials (to April 2011) Cochrane Central Register of Controlled Trials (to April 2011), MEDLINE (from 1950 to October 2010), EMBASE (from 1980 to October 2010) and the reference lists of articles. SELECTION CRITERIA: Randomised controlled trials comparing different durations of SC (seven days or fewer or more than seven days). Other interventions, e.g. bronchodilators and antibiotics, were standardised; studies in other lung diseases were excluded, unless data on participants with COPD were available. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data that were pooled them using Review Manager 5. We sought missing data from authors of studies published as abstracts only. MAIN RESULTS: We identified seven studies including 288 participants; two studies were fully published and five were published as abstracts. We obtained data for two studies published as abstracts from authors; these two abstracts and the two full papers contributed to meta-analysis. No study specified COPD diagnostic criteria and only one specified exacerbation criteria. Short course treatment varied between three and seven days and longer duration 10 to 15 days, at equivalent daily doses of corticosteroids; five studies used oral prednisolone (dose 30 mg, four studies, one tapered dose) and two studies used intravenous corticosteroid treatment. Mean ages of participants ranged from 64 to 73 years. We assessed the risk of allocation and blinding bias as low for these studies. PRIMARY OUTCOMES: risk of treatment failure did not differ significantly by treatment duration, but the confidence interval (CI) was too wide to conclude equivalence (Peto odds ratio (OR) 0.82; 95% CI 0.24 to 2.79) (three studies, n = 146). Forced expiratory volume in 1 second (FEV1) did not differ significantly when measured up to seven days (mean difference (MD) -0.07 L; 95% CI -0.19 to 0.05) or after seven days (MD -0.02 L;95% CI -0.10 to 0.06) in four studies (n = 187). The likelihood of an adverse event (four studies, n = 192) did not differ significantly by treatment duration, but again the CI was wide (OR 0.58, 95% CI 0.14 to 2.40). AUTHORS' CONCLUSIONS: We based assessment of the efficacy of short (seven days or less) compared to longer duration (more than seven days) systemic corticosteroid therapy for acute exacerbations of COPD in this review on four of the seven included studies for which data were available. Two studies were fully published and two were published as conference abstracts but trialists were able to supply data requested for the review.The finding in this review that there is no significant increase in treatment failure with shorter systemic corticosteroid treatment for seven days or less for acute exacerbations of COPD, does not give conclusive evidence to recommend change in clinical practice due to a wide confidence interval around the estimate of effect. The four studies which contributed to the meta-analysis were of relatively low quality and five of the seven studies were not published as full articles. Thus there are insufficient data to allow firm conclusions concerning the optimal duration of corticosteroid therapy of acute exacerbations of COPD to be drawn. PMID- 21975758 TI - Neonatal vitamin A supplementation for the prevention of mortality and morbidity in term neonates in developing countries. AB - BACKGROUND: Vitamin A deficiency is a major public health problem in developing countries. Vitamin A supplementation in children greater than six months of age has been found to be beneficial, with no effect of supplementation between one to five months. Supplementation in the neonatal period has been suggested to have an impact by increasing body stores in early infancy. OBJECTIVES: To evaluate the role of vitamin A supplementation in term neonates in developing countries with respect to the prevention of mortality and morbidity. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, May 2010), EMBASE and MEDLINE (1966 to May 2010) via PubMed. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials. Trials with factorial designs were also included. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted the data. MAIN RESULTS: Seven trials (51,446 neonates) were included in this review, with only few trials reporting disaggregated data for term infants. Therefore, we analysed data and presented estimates for term infants (where specified) followed by all infants.Data for term neonates from three studies showed a statistically significant effect on the risk of infant mortality at six months in the vitamin A group compared with the control group (typical risk ratio (RR) 0.82; 95% CI 0.68 to 0.99; I(2) 63%). Analysis of data for all infants from five studies showed a 14% reduction in the risk of infant mortality at six months in neonates supplemented with vitamin A compared to control; this reduction was statistically significant (typical RR 0.86; 95% CI 0.77 to 0.97; I(2) 39%). These findings should be interpreted with caution, however, due to the small number of included studies, wide confidence intervals with upper levels close to the null effect and statistical heterogeneity. Vitamin A supplementation failed to show any significant effect on infant mortality at 12 months of age compared to control (typical rate ratio 1.03; 95% CI 0.87 to 1.23; I(2) 49%). Limited data were available for the outcomes of cause-specific mortality and morbidity, vitamin A deficiency, anaemia and adverse events. AUTHORS' CONCLUSIONS: Considering mortality in early infancy being a major contributory cause of overall child mortality for the under five year old group in developing countries, it is critical to obtain sound scientific evidence of the effect of vitamin A supplementation in neonates. Evidence provided in this review does indicate a potential beneficial effect of supplementing neonates with vitamin A at birth for reducing mortality in the first half of infancy. Considering the absence of a clear indication of the biological mechanism and conflicting findings from individual studies in settings with varying levels of maternal vitamin A deficiency and infant mortality, and given four additional ongoing trials with approximately 100,000 neonates being enrolled, we propose a delay in any policy recommendations for neonatal vitamin A supplementation. PMID- 21975759 TI - Inhaled corticosteroids versus long-acting beta(2)-agonists for chronic obstructive pulmonary disease. AB - BACKGROUND: Long-acting beta(2)-agonists and inhaled corticosteroids can be used as maintenance therapy by patients with moderate to severe chronic obstructive pulmonary disease. These interventions are often taken together in a combination inhaler. However, the relative added value of the two individual components is unclear. OBJECTIVES: To determine the relative effects of inhaled corticosteroids (ICS) compared to long-acting beta(2)-agonists (LABA) on clinical outcomes in patients with stable chronic obstructive pulmonary disease. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register of trials (latest search August 2011) and reference lists of articles. SELECTION CRITERIA: We included randomised controlled trials comparing inhaled corticosteroids and long-acting beta(2)-agonists in the treatment of patients with stable chronic obstructive pulmonary disease. DATA COLLECTION AND ANALYSIS: Three authors independently assessed trials for inclusion and then extracted data on trial quality, study outcomes and adverse events. We also contacted study authors for additional information. MAIN RESULTS: We identified seven randomised trials (5997 participants) of good quality with a duration of six months to three years. All of the trials compared ICS/LABA combination inhalers with LABA and ICS as individual components. Four of these trials included fluticasone and salmeterol monocomponents and the remaining three included budesonide and formoterol monocomponents. There was no statistically significant difference in our primary outcome, the number of patients experiencing exacerbations (odds ratio (OR) 1.22; 95% CI 0.89 to 1.67), or the rate of exacerbations per patient year (rate ratio (RR) 0.96; 95% CI 0.89 to 1.02) between inhaled corticosteroids and long-acting beta(2)-agonists. The incidence of pneumonia, our co-primary outcome, was significantly higher among patients on inhaled corticosteroids than on long acting beta(2)-agonists whether classified as an adverse event (OR 1.38; 95% CI 1.10 to 1.73) or serious adverse event (Peto OR 1.48; 95% CI 1.13 to 1.93). Results of the secondary outcomes analysis were as follows. Mortality was higher in patients on inhaled corticosteroids compared to patients on long-acting beta(2)-agonists (Peto OR 1.17; 95% CI 0.97 to 1.42), although the difference was not statistically significant. Patients treated with beta(2)-agonists showed greater improvements in pre-bronchodilator FEV(1) compared to those treated with inhaled corticosteroids (mean difference (MD) 18.99 mL; 95% CI 0.52 to 37.46), whilst greater improvements in health-related quality of life were observed in patients receiving inhaled corticosteroids compared to those receiving long acting beta(2)-agonists (St George's Respiratory Questionnaire (SGRQ) MD -0.74; 95% CI -1.42 to -0.06). In both cases the differences were statistically significant but rather small in magnitude. There were no statistically significant differences between ICS and LABA in the number of hospitalisations due to exacerbations, number of mild exacerbations, peak expiratory flow, dyspnoea, symptoms scores, use of rescue medication, adverse events, all cause hospitalisations, or withdrawals from studies. AUTHORS' CONCLUSIONS: Placebo controlled trials have established the benefits of both long-acting beta-agonist and inhaled corticosteroid therapy for COPD patients as individual therapies. This review, which included trials allowing comparisons between LABA and ICS, has shown that the two therapies confer similar benefits across the majority of outcomes, including the frequency of exacerbations and mortality. Use of long acting beta-agonists appears to confer a small additional benefit in terms of improvements in lung function compared to inhaled corticosteroids. On the other hand, inhaled corticosteroid therapy shows a small advantage over long-acting beta-agonist therapy in terms of health-related quality of life, but inhaled corticosteroids also increase the risk of pneumonia. This review supports current guidelines advocating long-acting beta-agonists as frontline therapy for COPD, with regular inhaled corticosteroid therapy as an adjunct in patients experiencing frequent exacerbations. PMID- 21975760 TI - Tocolytics for preterm premature rupture of membranes. AB - BACKGROUND: In women with preterm labor, tocolysis has not been shown to improve perinatal mortality; however, it is often given for 48 hours to allow for the corticosteroid effect for fetal maturation. In women with preterm premature rupture of membranes (PPROM), the use of tocolysis is still controversial. In theory, tocolysis may prolong pregnancy in women with PPROM, thereby allowing for the corticosteroid benefit and reducing the morbidity and mortality associated with prematurity. OBJECTIVES: To assess the potential benefits and harms of tocolysis in women with preterm premature rupture of membranes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (6 April 2011), CENTRAL (The Cochrane Library 2011, Issue 1), MEDLINE (1966 to 6 April 2011) and EMBASE (1974 to 6 April 2011). SELECTION CRITERIA: We included pregnant women with singleton pregnancies and PPROM (23 weeks to 36 weeks and six days). We included any tocolytic therapy compared to no tocolytic, placebo, or another tocolytic. DATA COLLECTION AND ANALYSIS: All review authors assessed the studies for inclusion. We extracted and quality assessed data. MAIN RESULTS: We included eight studies with a total of 408 women. Seven of the studies compared tocolysis to no tocolysis. One study compared nifedipine to terbutaline. Compared to no tocolysis, tocolysis was not associated with a significant effect on perinatal mortality in women with PPROM (risk ratio (RR) 1.67; 95% confidence interval (CI) 0.85 to 3.29). Tocolysis was associated with longer latency (mean difference (MD) 73.12 hours; 95% CI 20.21 to 126.03; three trials of 198 women) and fewer births within 48 hours (average RR 0.55; 95% CI 0.32 to 0.95; six trials of 354 women; random-effects, T(2) = 0.18, I(2) = 43%) compared to no tocolysis. However, tocolysis was associated with increased five-minute Apgar of less than seven (RR 6.05; 95% CI 1.65 to 22.23; two trials of 160 women) and increased need for ventilation of the neonate (RR 2.46; 95% CI 1.14 to 5.34; one trial of 81 women). In the subgroup analysis comparing betamimetic to no betamimetics, tocolysis was associated with increased latency and borderline significance for chorioamnionitis. Prophylactic tocolysis with PPROM was associated with increased overall latency, without additional benefits for maternal/neonatal outcomes. For patients with PPROM before 34 weeks, there was a significantly increased risk of chorioamnionitis in women who received tocolysis. However, neonatal outcomes were not significantly different. There were no significant differences in maternal/neonatal outcomes in subgroup analyses comparing cox inhibitor versus no tocolysis, calcium channel blocker versus betamimetic, antibiotic, corticosteroid or combined antibiotic/corticosteroid. AUTHORS' CONCLUSIONS: Our review suggests there is insufficient evidence to support tocolytic therapy for women with PPROM, as there was an increase in maternal chorioamnionitis without significant benefits to the infant. However, studies did not consistently administer latency antibiotics and corticosteroids, both of which are now considered standard of care. PMID- 21975761 TI - Calcium supplementation (other than for preventing or treating hypertension) for improving pregnancy and infant outcomes. AB - BACKGROUND: Maternal nutrition during pregnancy is known to have an effect on fetal growth and development. It is recommended that women increase their calcium intake during pregnancy and lactation, although the recommended dosage varies among professionals. Currently, there is no consensus on the role of routine calcium supplementation for pregnant women other than for preventing or treating hypertension. OBJECTIVES: To determine the effect of calcium supplementation on maternal, fetal and neonatal outcomes (other than for preventing or treating hypertension) as well as any possible side effects. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (17 March 2011). SELECTION CRITERIA: We considered all published, unpublished and ongoing randomised controlled trials (RCTs) comparing maternal, fetal and neonatal outcomes in pregnant women who received calcium supplementation versus placebo or no treatment. We excluded quasi- and pseudo-RCTs. DATA COLLECTION AND ANALYSIS: Two review authors identified studies for inclusion and extracted the data. Two review authors performed data analysis. MAIN RESULTS: This review includes data from 21 studies (involving 16,602 women). There were no statistically significant differences between women who received calcium supplementation and those who did not in terms of reducing preterm births (less than 37 weeks' gestation) (risk ratio (RR) 0.90; 95% confidence interval (CI) 0.73 to 1.11; 12 studies, 15615 women; random-effects model) and also in less than 34 weeks' gestation (RR 1.11; 95% CI 0.84 to 1.46; three trials, 5145 women). There was no significant difference in infant low birth weight between the two groups (RR 0.91; 95% CI 0.72 to 1.16; four trials, 13449 infants; random-effects). However, compared to the control group, women in the calcium supplementation group gave birth to slightly heavier birth weight infants (mean difference (MD) 64.66 g; 95% CI 15.75 to 113.58; 19 trials, 8287 women; random-effects). AUTHORS' CONCLUSIONS: Calcium supplementation is associated with a significant protective benefit in the prevention of pre-eclampsia, and should be used for this indication according to a previous review. This review indicates that there are no additional benefits for calcium supplementation in prevention of preterm birth or low infant birth weight. While there was a statistically significant difference of 80 g identified in mean infant birth weight, there was significant heterogeneity identified, and the clinical significance of this difference is uncertain. PMID- 21975762 TI - Dance/movement therapy for improving psychological and physical outcomes in cancer patients. AB - BACKGROUND: Current cancer care increasingly incorporates psychosocial interventions. Cancer patients use dance/movement therapy to learn to accept and reconnect with their bodies, build new self-confidence, enhance self-expression, address feelings of isolation, depression, anger and fear and to strengthen personal resources. OBJECTIVES: To compare the effects of dance/movement therapy and standard care with standard care alone or standard care and other interventions in patients with cancer. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, Science Citation Index, CancerLit, International Bibliography of Theatre and Dance, Proquest Digital Dissertations, ClinicalTrials.gov, Current Controlled Trials and the National Research Register (all to March 2011). We handsearched dance/movement therapy and related topics journals, reviewed reference lists and contacted experts. There was no language restriction. SELECTION CRITERIA: We included all randomized and quasi-randomized controlled trials of dance/movement therapy interventions for improving psychological and physical outcomes in patients with cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data and assessed the methodological quality. Results were presented using standardized mean differences. MAIN RESULTS: We included two studies with a total of 68 participants. No evidence was found for an effect of dance/movement therapy on body image in women with breast cancer. The data of one study with moderate risk of bias suggested that dance/movement therapy had a large beneficial effect on participants' quality of life (QoL). The second trial reported a large beneficial effect on fatigue. However, this trial was at high risk of bias. The individual studies did not find support for an effect of dance/movement therapy on mood, distress,and mental health. It is unclear whether this was due to ineffectiveness of the treatment or limited power of the trials. Finally, the results of one study did not find evidence for an effect of dance/movement therapy on shoulder range of motion (ROM) or arm circumference in women who underwent a lumpectomy or breast surgery. However, this was likely due to large within-group variability for shoulder ROM and a limited number of participants with lymphedema. AUTHORS' CONCLUSIONS: We did not find support for an effect of dance/movement therapy on body image. The findings of one study suggest that dance/movement therapy may have a beneficial effect on QoL. However, the limited number of studies prevents us from drawing conclusions concerning the effects of dance/movement therapy on psychological and physical outcomes in cancer patients. PMID- 21975763 TI - Different strategies for diagnosing gestational diabetes to improve maternal and infant health. AB - BACKGROUND: Gestational diabetes mellitus (GDM) is carbohydrate intolerance resulting in hyperglycaemia with onset or first recognition during pregnancy. If untreated, perinatal morbidity and mortality may be increased. Accurate diagnosis allows appropriate treatment. OBJECTIVES: To evaluate and compare alternative tests for diagnosis of GDM, in terms of maternal and infant health and use of health service resources. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2011). SELECTION CRITERIA: We included randomised trials if they evaluated tests carried out to diagnose GDM. We excluded studies that used a quasi-random model. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, trial quality and extracted data. MAIN RESULTS: We identified five small trials, including 578 women. One trial compared three different methods of delivering glucose: a candy bar (39 women), a 50 g glucose polymer drink (40 women) and a 50 g glucose monomer drink (43 women). We have reported results for this trial as two separate comparisons.75 g oral glucose tolerance test (OGTT) versus a 100 g OGTT (one trial, 248 women): women given the 75 g OGTT had a higher relative risk of being diagnosed with GDM (risk ratio (RR) 2.55, 95% confidence interval (CI) 0.96 to 6.75).This difference was borderline for statistical significance. No other measures of maternal morbidity, or outcome for the baby were reported.Candy bar versus 50 g glucose monomer drink (one trial, 82 women): women receiving the candy bar, rather than glucose monomer, reported fewer side effects (RR 0.50, 95% CI 0.26 to 0.97) and preferred the taste (RR 0.62, 95% CI 0.44 to 0.87). No outcomes were reported for the baby.50 g glucose polymer versus 50 g glucose monomer (three trials, 259 women): mean difference (MD) in gestation at birth was -0.80 weeks (one trial, 100 women; 95% CI -1.69 to 0.09). Side effects were less common with the glucose polymer (one trial 82 women; RR 0.20 95% CI 0.07 to 0.54), with no clear difference in taste acceptability (one trial 83 women; RR 0.96; 95% CI 0.78 to 1.18). Significantly fewer women reported nausea following the 50 g glucose polymer drink compared to the 50 g glucose monomer drink (one trial 66 women; RR 0.29; 95% CI 0.11 to 0.78) and bloatedness (two trials 149 women; RR 0.22; 95% CI 0.08 to 0.60). No other measures of maternal morbidity or outcome for the baby were reported.50 g glucose in food versus 50 g glucose drink (one trial, 30 women): women receiving glucose in their food, rather than as a drink, reported fewer side effects (RR 0.08, 95% CI 0.01 to 0.56). There was no clear difference in number of women requiring further testing (RR 0.14, 95% CI 0.01 to 2.55). No other measures of maternal morbidity or outcome for the baby were reported. AUTHORS' CONCLUSIONS: There is insufficient evidence to assess which is the best strategy for diagnosing GDM. PMID- 21975764 TI - Single dose intravenous propacetamol or intravenous paracetamol for postoperative pain. AB - BACKGROUND: Paracetamol (acetaminophen) is the most commonly prescribed analgesic for the treatment of acute pain. It may be administered orally or intravenously. The efficacy and safety of intravenous (IV) formulations of paracetamol, IV paracetamol and IV propacetamol, compared with placebo and other analgesics, is unclear. OBJECTIVES: To assess the efficacy and safety of IV formulations of paracetamol for treatment of postoperative pain in both adults and children. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 2), MEDLINE (1950 to May 2010), EMBASE (1980 to 2010, Week 18), LILACS (1992 to May 2010) and reference lists of retrieved articles. SELECTION CRITERIA: Randomized, double-blind, placebo- or active-controlled single dose clinical trials of IV propacetamol or IV paracetamol for acute postoperative pain in adults or children. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risk of bias and extracted data. We contacted study authors for additional information. We collected adverse event information from the studies. MAIN RESULTS: Thirty-six studies (3896 participants) were included. Thirty-seven percent of participants receiving IV propacetamol/paracetamol experienced at least 50% pain relief over four hours compared with 16% of those receiving placebo (number needed to treat to benefit (NNT = 4.0; 95% confidence interval 3.5 to 4.8). The proportion of participants in IV propacetamol/paracetamol groups experiencing at least 50% pain relief diminished over six hours, as reflected in a higher NNT of 5.3 (4.2 to 6.7). Participants receiving IV propacetamol/paracetamol required 30% less opioid over four hours than those receiving placebo. However, this did not translate to a reduction in opioid-induced adverse events.Meta-analysis of efficacy comparisons between IV propacetamol/paracetamol and active comparators (opioids or nonsteroidal anti-inflammatories (NSAIDs)) were either not statistically significant, not clinically significant, or both.Adverse events occurred at similar rates with IV propacetamol or IV paracetamol and placebo. However, pain on infusion occurred more frequently in those receiving IV propacetamol versus placebo (23% versus 1%).Meta-analysis did not demonstrate statistically significant differences between IV propacetamol/paracetamol and active comparators for any adverse event except a reduction in the rate of hypotension versus NSAIDs and a reduction in the rate of gastrointestinal disorders versus opioids. AUTHORS' CONCLUSIONS: A single dose of both IV propacetamol and IV paracetamol provides around four hours of effective analgesia for about 37% of patients with acute postoperative pain. Both formulations are associated with few adverse events, although patients receiving IV propacetamol have a higher incidence of pain on infusion than both placebo and IV paracetamol. PMID- 21975765 TI - Oral lactoferrin for the prevention of sepsis and necrotizing enterocolitis in preterm infants. AB - BACKGROUND: Lactoferrin, a normal component of human colostrum, milk, tears and saliva can enhance host defence and may be effective in the prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates. OBJECTIVES: To assess the safety and effectiveness of oral lactoferrin in the prevention of sepsis and NEC in preterm neonates. SEARCH STRATEGY: We used the search strategy of the Cochrane Neonatal Review Group (CNRG) including searches of CENTRAL (The Cochrane Library), MEDLINE and PREMEDLINE, EMBASE and CINAHL. We also searched trials registries and the conference proceedings of Pediatric Academic Society. Searches updated in July 2011. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials evaluating oral lactoferrin at any dose or duration for the prophylaxis of sepsis or NEC in preterm neonates. DATA COLLECTION AND ANALYSIS: Data collection and analysis were performed according to the standard methods of the CNRG. MAIN RESULTS: One trial (Manzoni 2008) that randomized 472 very low birth weight infants was eligible. A statistically significant reduction in late onset sepsis was observed in the groups that received either lactoferrin alone (RR 0.34, 95% CI 0.17 to 0.70) or in combination with Lactobacillus rhamnosus GG (RR 0.27, 95% CI 0.12 to 0.60).In subgroup analyses, infants weighing less than 1000 g and those fed exclusively on maternal milk had a significant reduction in late-onset sepsis after oral lactoferrin supplementation alone. In the group supplemented with oral lactoferrin and Lactobacillus rhamnosus, infants weighing less than 1000 g had a significant reduction in late-onset sepsis, a result not seen in infants fed maternal milk exclusively.Prophylaxis with oral lactoferrin alone did not reduce the incidence of NEC (RR 0.33, 95% CI 0.09 to 1.17), but a significant reduction in NEC with a combination of lactoferrin and Lactobacillus rhamnosus GG was noted (RR 0.05, 95% CI 0.00 to 0.90).No adverse effects due to lactoferrin were observed in this study. Long-term neurological outcomes were not assessed in this trial. AUTHORS' CONCLUSIONS: Oral lactoferrin prophylaxis reduces the incidence of late-onset sepsis in infants weighing less than 1500 g and most effective in infants weighing less than 1000 g. There is no evidence of efficacy of oral lactoferrin (given alone) in the prevention of NEC in preterm neonates.Well designed, randomized trials should address dosing, duration, type of lactoferrin (bovine or human) prophylaxis in prevention of sepsis and NEC. The effect of exclusive maternal milk feeding should be clarified. PMID- 21975766 TI - Oral lactoferrin for the treatment of sepsis and necrotizing enterocolitis in neonates. AB - BACKGROUND: Neonatal sepsis and necrotizing enterocolitis (NEC) cause significant neonatal mortality and morbidity in spite of appropriate antibiotic therapy. Enhancing host defence and modulating inflammation by using lactoferrin as an adjunct to antibiotics in the treatment of sepsis and/or NEC may improve clinical outcomes. OBJECTIVES: The primary objective is to assess safety and efficacy of oral lactoferrin as an adjunct to antibiotics in the treatment of neonates with suspected or confirmed sepsis and/or NEC. SEARCH STRATEGY: Relevant trials in any language were searched in July 2011 in the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, PREMEDLINE, EMBASE, CINAHL, web sites: www.clinicaltrials.gov and www.controlled-trials.com, abstracts from the annual meeting of Pediatric Academic Societies (1990 to July 2011), by contacting authors who have published in this field, from the reference lists of identified clinical trials and in the reviewer's personal files. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials evaluating oral lactoferrin (at any dose or duration) used as an adjunct to antibiotic therapy compared with antibiotic therapy alone (with or without placebo) or other adjuncts to antibiotic therapy to treat neonates at any gestational age up to 44 weeks postmenstrual age with confirmed or suspected sepsis or necrotizing enterocolitis (Bell's Stage II or III). DATA COLLECTION AND ANALYSIS: We used the standardized methods of the Cochrane Neonatal Review Group (CNRG) for conducting a systematic review and for assessing the methodological quality of the studies (http://neonatal.cochrane.org/en/index.html). The titles and the abstracts of studies identified by the search strategy were independently assessed by the two review authors and full text version was obtained for assessment if necessary. Forms were designed for trial inclusion/exclusion and data extraction. MAIN RESULTS: We did not identify any eligible neonatal trial evaluating lactoferrin for treatment of neonatal sepsis or NEC. AUTHORS' CONCLUSIONS: IMPLICATIONS FOR PRACTICE: Currently there is no evidence to recommend or refute the use of lactoferrin for the treatment of neonatal sepsis or necrotizing enterocolitis as an adjunct to antibiotic therapy. IMPLICATIONS FOR RESEARCH: The safety and efficacy of different preparations and doses of lactoferrin need to be established in neonates. Well designed adequately powered randomized multicenter trials are needed to address the efficacy and safety of lactoferrin in the treatment of neonatal sepsis and necrotizing enterocolitis. These trials should evaluate long-term neurodevelopmental and pulmonary outcomes in addition to short term outcomes. PMID- 21975767 TI - High dose versus low dose oxytocin for augmentation of delayed labour. AB - BACKGROUND: A major cause of failure to achieve spontaneous vaginal birth is delay in labour caused by presumed inefficient uterine action. High dose may potentially increase the number of spontaneous vaginal births, but as oxytocin can cause hyperstimulation of the uterus, there is a possibility of increased adverse events. OBJECTIVES: To compare starting dose and increment of amount of oxytocin for augmentation for women delayed in labour to determine whether augmentation by high dose of oxytocin improves labour outcomes and the effect on both maternal/neonatal outcomes and women's birth experiences. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 February 2011) and reference lists of retrieved studies. SELECTION CRITERIA: We included all randomised and quasi-randomised controlled trials for women in delayed in labour requiring augmentation by oxytocin comparing high starting and increment dose (defined as starting dose and increment of equal to or more than 4 mU per minute) with low dose (defined as starting dose and an increment of less than 4 mU per minute. Increase interval: between 15 and 40 minutes. The separation of low and high doses is based on an arbitrary decision. DATA COLLECTION AND ANALYSIS: Three review authors undertook assessment of trial eligibility, risk of bias, and data extraction independently. MAIN RESULTS: We included four studies involving 660 pregnant women. Three studies were randomised controlled trials and one trial was a quasi-randomised study. A higher dose of oxytocin was associated with a significant reduction in length of labour reported from one trial (mean difference (MD) -3.50 hours; 95% confidence interval (CI) 6.38 to -0.62; one trial, 40 women). There was a decrease in rate of caesarean section (risk ratio (RR) 0.53; 95% CI 0.38 to 0.75, four trials, 650 women) and an increase in the rate of spontaneous vaginal birth (RR 1.37; 95% CI 1.15 to 1.64, two trials, 350 women). There were no significant differences for neonatal mortality, hyperstimulation, chorioamnionitis, epidural analgesia; or neonatal outcomes of Apgar scores, umbilical cord pH or admission to special care baby unit. The following outcomes were not evaluated in the included studies: perinatal mortality, women's satisfaction, instrumental vaginal birth, uterine rupture, postpartum haemorrhage, abnormal cardiotocography, women's pyrexia, dystocia and neonatal neurological morbidity. AUTHORS' CONCLUSIONS: Higher dose of oxytocin starting and increment dose (4 mU per minute or more) was associated with a reduction in the length of labour and in caesarean section, and an increase in spontaneous vaginal birth. However, there is insufficient evidence. The number of studies and the quality of the available evidence is of concern. Additionally, there is insufficient evidence for other maternal and neonatal outcomes, and how women feel about the higher doses of oxytocin. Therefore, no firm recommendation can be made. Further research should evaluate the effect of high dose oxytocin for women delayed in labour and should include these outcomes. PMID- 21975768 TI - Zinc supplementation as an adjunct to antibiotics in the treatment of pneumonia in children 2 to 59 months of age. AB - BACKGROUND: Diarrhoeal disorders and acute respiratory infections (ARIs), especially pneumonia, are the most common causes of death in low-income countries. Studies evaluating the impact of zinc supplementation as an adjunct in the management of pneumonia are limited and have shown variable results. OBJECTIVES: To evaluate zinc supplementation, as an adjunct to antibiotics, in the treatment (clinical recovery) of pneumonia in children aged two to 59 months. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), which contains the Cochrane Acute Respiratory Infections (ARI) Group's and the Cochrane Infectious Diseases Group's Specialised Registers, MEDLINE (1950 to March week 2, 2011), EMBASE (1974 to March 2011), CINAHL (1981 to March 2011), LILACS (1985 to March 2011), AMED (1985 to March 2011), CAB Abstracts (1910 to March 2011) and Web of Science (2000 to March 2011). SELECTION CRITERIA: Randomised control trials (RCTs) evaluating supplementation of zinc as an adjunct to antibiotics for pneumonia in children aged two to 59 months. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and screened all available titles and abstracts for inclusion. If the relevance could not be ascertained by screening the title and abstract, we retrieved and reviewed the full text of the article. MAIN RESULTS: We included four trials in which 3267 children aged two to 35 months participated. Analysis showed that zinc supplementation in addition to standard antibiotic therapy in children with severe and non-severe pneumonia failed to show a statistically significant effect on clinical recovery (risk ratio (RR) 1.02; 95% confidence interval (CI) 0.93 to 1.11). Similary, zinc supplementation in children with severe pneumonia, as an adjunct to standard antibiotic therapy, did not show a statistically significant effect on clinical recovery measured as resolution of tachypnoea (respiratory rate > 50 breaths per minute) (RR 1.13; 95% CI 0.82 to 1.57) and cessation of chest indrawing (RR 1.08; 95% CI 0.88 to 1.31) as compared to the control group. Zinc supplementation in children with severe pneumonia also showed a non-significant effect on the duration of hospitalization stay as compared to the control (RR 1.04; 95% CI 0.89 to 1.22). AUTHORS' CONCLUSIONS: Evidence provided in this review is insufficient to recommend the use of zinc as an adjunct to standard antibiotic therapy for pneumonia in children aged two to 35 months. PMID- 21975769 TI - Interventions for treatment of neonatal hyperglycemia in very low birth weight infants. AB - BACKGROUND: Early neonatal hyperglycemia is common among very low birth weight (VLBW) neonates. Increased risks for death and major morbidities have been observed among VLBW neonates who develop hyperglycemia. It is uncertain whether the hyperglycemia per se is a cause of adverse clinical outcomes or whether the incidence of adverse outcomes can be reduced by treatment. OBJECTIVES: To assess the effects on clinical outcomes of interventions for treating neonatal hyperglycemia in the VLBW neonate receiving total or partial parenteral nutrition. SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4 of 12, 2011), MEDLINE (1966 to April 2011), EMBASE (1980 to April 2011) and CINAHL (1982 to July 2008). We searched for abstracts submitted for the annual meetings of Pediatric Academic Societies 2000 to 2011 and The European Society for Pediatric Research 2005 to 2010. SELECTION CRITERIA: Randomized or quasi-randomized trials of interventions for the treatment of hyperglycemia in hyperglycemic VLBW neonates were eligible for inclusion in this review. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for eligibility and extracted data on study design, methodology, clinical features, and treatment outcomes. Additional information on study design and outcomes was obtained from the lead investigator of each of the two included trials. The included trials were assessed for blinding of randomization, blinding of caretakers to the intervention, completeness of follow-up, and blinding of outcome measurement. The treatment effect measures for categorical outcomes were relative risk (RR) and risk difference (RD) with their 95% confidence intervals (CI); for continuous outcomes the measure was mean difference and 95% CI. MAIN RESULTS: Only two eligible trials were found (Collins 1991; Meetze 1998). Both were randomized but of very small size (24 and 23 neonates randomized in each trial, respectively).No trial compared reduction versus no reduction of glucose infusion.Collins 1991 compared insulin infusion with standard care. Insulin infusion had no significant effect on death or bacterial sepsis; effects on other major morbidities were not assessed. Insulin infusion resulted in significant increases in non-protein energy intake, glucose intake, and short-term weight gain.Meetze 1998 compared insulin infusion with reduction of glucose infusion. Insulin infusion had no significant effects on death, severe intraventricular hemorrhage, retinopathy of prematurity, bacterial sepsis, fungal sepsis, or necrotizing enterocolitis; effects on other major morbidities were not assessed. Insulin infusion resulted in significant increases in glucose intake and total energy intake. AUTHORS' CONCLUSIONS: Evidence from randomized trials in hyperglycemic VLBW neonates is insufficient to determine the effects of treatment on death or major morbidities. It remains uncertain whether the hyperglycemia per se is a cause of adverse clinical outcomes or how the hyperglycemia should be treated. Much larger randomized trials in hyperglycemic VLBW neonates that are powered on clinical outcomes are needed in order to determine whether, and how, the hyperglycemia should be treated. PMID- 21975770 TI - Vitamin A supplementation for the prevention of morbidity and mortality in infants six months of age or less. AB - BACKGROUND: Vitamin A deficiency is a significant public health problem in low and middle income countries. Vitamin A supplementation (VAS) provided to lactating postpartum mothers or to infants less than six months of age are two possible strategies to improve the nutrition of infants at high risk of vitamin A deficiency and thus potentially reduce their mortality and morbidity. OBJECTIVES: To evaluate the effect of:1. VAS in postpartum breast feeding mothers in low and middle income countries, irrespective of antenatal VAS status, on mortality, morbidity and adverse effects in their infants up until the age of one year.2. VAS initiated in the first half of infancy (< 6 months of age) in low and middle income countries, irrespective of maternal antenatal or postnatal VAS status, on mortality, morbidity and adverse effects up until the age of one year. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), EMBASE, MEDLINE, clinical trials websites, conference proceedings, donor agencies, 'experts' and researchers (up to October 15, 2010). SELECTION CRITERIA: Randomized or quasi-randomised, individually or cluster randomised, placebo controlled trials involving synthetic VAS provided to the postpartum mothers or their infants up to the age of six months were eligible. DATA COLLECTION AND ANALYSIS: Two review authors assessed the studies for their risk of bias and collected data on outcomes. MAIN RESULTS: Of the 18 included studies, eight provided information on maternal VAS and 15 on infant VAS.For maternal VAS, there was no evidence of a reduced risk of mortality of their babies during infancy (96,203 participants, seven studies, high quality evidence; random-effects model RR 1.00, 95% CI 0.94 to 1.06, P = 0.9; test of heterogeneity I(2) = 0%, P = 0.9) or in the neonatal period (moderate quality evidence); nor of morbidities (very low quality evidence). For infant VAS, there was no evidence of a reduced risk of mortality during infancy (59,402 participants, nine studies, moderate quality evidence; random-effects model RR 0.97, 0.83 to 1.12, P = 0.65; test of heterogeneity I(2) = 49%, P = 0.05) or in the neonatal period, nor morbidities (low quality evidence), but an increased risk of bulging fontanelle (32,978 participants, 10 studies, low quality evidence; random-effects model RR 1.55, 1.05 to 2.28, P = 0.03; test of heterogeneity I(2) = 68%, P = 0.0009). AUTHORS' CONCLUSIONS: There is no convincing evidence that either maternal postpartum or infant vitamin A supplementation results in a reduction in infant mortality or morbidity in low and middle income countries. PMID- 21975771 TI - Short-course versus prolonged-course antibiotic therapy for hospital-acquired pneumonia in critically ill adults. AB - BACKGROUND: Pneumonia is the most common hospital-acquired infection affecting patients in the intensive care unit (ICU). However, the optimal duration of antibiotic therapy for hospital-acquired pneumonia (HAP) is uncertain. OBJECTIVES: To assess the effectiveness of short versus prolonged-course antibiotic administration for HAP in critically ill adults, including patients with ventilator-associated pneumonia (VAP). SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1950 to February week 4, 2011), EMBASE (1974 to March 2011), LILACS (1985 to March 2011) and Web of Science (1985 to March 2011). SELECTION CRITERIA: We considered all randomised controlled trials (RCTs) comparing fixed durations of antibiotic therapy, or comparing a protocol intended to limit duration of therapy with standard care, for HAP (including patients with VAP) in critically ill adults. DATA COLLECTION AND ANALYSIS: Two review authors conducted data extraction and assessment of risk of bias. We contacted trial authors for additional information. MAIN RESULTS: Eight studies (1703 patients) were included. Methodology varied considerably and we found little evidence regarding patients with a high probability of HAP who were not mechanically ventilated. For patients with VAP, a short seven to eight-day course of antibiotics compared with a prolonged 10 to 15-day course (three studies, N = 508) increased 28-day antibiotic-free days (odds ratio (OR) 4.02; 95% confidence interval (CI) 2.26 to 5.78) and reduced recurrence of VAP due to multi-resistant organisms (OR 0.44; 95% CI 0.21 to 0.95), without adversely affecting other outcomes. However, for cases of VAP due to non-fermenting Gram-negative bacilli (NF-GNB), recurrence was greater after short-course therapy (OR 2.18; 95% CI 1.14 to 4.16; two studies, N = 176), though other outcome measures did not significantly differ. Discontinuation strategies utilising clinical features (one study; N = 302) or procalcitonin (three studies; N = 323) led to a reduction in duration of therapy and, in the procalcitonin studies, increased 28-day antibiotic-free days (mean difference (MD) 2.80; 95% CI 1.39 to 4.21) without negatively affecting other outcomes. AUTHORS' CONCLUSIONS: We conclude that for patients with VAP not due to NF-GNB, a short fixed-course (seven or eight days) antibiotic therapy may be more appropriate than a prolonged course (10 to 15 days). Use of an individualised strategy (incorporating clinical features or serum procalcitonin) appears to safely reduce duration of antibiotic therapy for VAP. PMID- 21975772 TI - Interventions for prevention of neonatal hyperglycemia in very low birth weight infants. AB - BACKGROUND: Among very low birth weight (VLBW) infants, early neonatal hyperglycemia is common and is associated with increased risks for death and major morbidities. It is uncertain whether hyperglycemia per se is a cause of adverse clinical outcomes or whether outcomes can be improved by preventing hyperglycemia. OBJECTIVES: To assess effects on clinical outcomes of interventions for preventing hyperglycemia in VLBW neonates receiving full or partial parenteral nutrition. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, issue 4 of 12, 2011; MEDLINE (1966 to April 2011); EMBASE (1980 to April 2011); CINAHL (1982 to Nov 2008); abstracts of Pediatric Academic Societies 2000 to 2011 and European Society for Pediatric Research 2005 to 2010. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials of interventions for prevention of hyperglycemia in neonates with birth weight < 1500 g or gestational age < 32 wk. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for eligibility and extracted data on study design, methods, clinical features, and treatment outcomes. Included trials were assessed for blinding of randomization, intervention and outcome measurement, and completeness of follow up. Treatment effect measures for categorical outcomes were relative risk and risk difference, and for continuous outcomes, mean difference, each with their 95% confidence intervals. MAIN RESULTS: We detected four eligible trials. Two trials compared lower versus higher rates of glucose infusion in the early postnatal period. These trials were too small to assess effects on mortality or major morbidities. Two trials, one a moderately large multicentre trial (NIRTURE, Beardsall 2008), compared insulin infusion with standard care. Insulin infusion reduced hyperglycemia but increased death before 28 days and hypoglycemia. Reduction in hyperglycemia was not accompanied by significant effects on major morbidities; effects on neurodevelopment are awaited. AUTHORS' CONCLUSIONS: Glucose infusion rate: There is insufficient evidence from trials comparing lower with higher glucose infusion rates to inform clinical practice. Large randomized trials are needed, powered on clinical outcomes including death, major morbidities and adverse neurodevelopment.Insulin infusion: The evidence reviewed does not support the routine use of insulin infusions to prevent hyperglycemia in VLBW neonates. Further randomized trials of insulin infusion may be justified. They should enrol extremely low birth weight neonates at very high risk for hyperglycemia and neonatal death. They might use real time glucose monitors if these are validated for clinical use. Refinement of algorithms to guide insulin infusion is needed to enable tight control of glucose concentrations within the target range. PMID- 21975773 TI - Natalizumab for relapsing remitting multiple sclerosis. AB - BACKGROUND: Natalizumab (NTZ) (Tysabri((r))) is a monoclonal antibody that inhibits leukocyte migration across the blood-brain barrier, thus reducing inflammation in central nervous system, and has been approved worldwide for the treatment of relapsing-remitting multiple sclerosis (RRMS). OBJECTIVES: To evaluate the efficacy, tolerability and safety of NTZ in the treatment of patients with RRMS. SEARCH STRATEGY: We searched the Cochrane Multiple Sclerosis Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2010, Issue 1), MEDLINE (PubMed) and EMBASE, all up to 19 February 2010, and bibliographies of papers. Handsearching was carried out. Trialists and pharmaceutical companies were contacted. Furthermore, the websites of US Food and Drug Administration (FDA), the European Medicines Evaluation Agency (EMA) and the National Institute for health and Clinical Excellence (NICE) were also checked. SELECTION CRITERIA: All double-blind, randomised, controlled trials analysing more than a single infusion of NTZ (dosage > 3 mg/kg intravenous infusion every 4 weeks), also including its use as add-on treatment, versus placebo or other drugs in patients with RRMS. No restrictions on the basis of duration of treatment or length of follow up. DATA COLLECTION AND ANALYSIS: Three reviewers independently selected articles which met the inclusion criteria. Disagreements were solved by discussion. Two reviewers independently extracted the data and assessed the methodological quality of each trial. Missing data was sought by contacting principal authors and Biogen Idec, through Biogen-Dompe Italia. MAIN RESULTS: Three studies met the inclusion criteria. These included one placebo-controlled trial (942 patients) and two add-on placebo-controlled trials, i.e. one plus glatiramer acetate (110 patients) and the second plus interferon beta-1a (1171 patients).This review assessed the efficacy, tolerability and safety of NTZ in patients with RRMS. Data was conclusive with respect to efficacy and tolerability, but not safety. As far as efficacy is concerned, the results showed statistically significant evidence in favour of NTZ for all the primary outcomes and for the secondary ones where data was available. NTZ reduced the risk of experiencing at least one new exacerbation at 2 years by about 40% and of experiencing progression at 2 years by about 25% as compared to a control group. MRI parameters showed statistical evidence in favour of participants receiving NTZ. Infusion reactions, anxiety, sinus congestion, lower limb swelling, rigors, vaginitis and menstrual disorders were reported as adverse events (AEs) more frequently after NTZ treatment. In this review NTZ was found to be well tolerated over a follow-up period of two years: the number of patients experiencing at least one AE (including severe and serious AEs) during this period did not differ between NTZ-treated patients and controls. Safety concerns have been raised about Progressive Multifocal Leukoencephalopathy (PML). In the trials included in this review, two cases of PML were encountered: one in a patient who had received 29 doses of NTZ and a second fatal case of PML in another patient after 37 doses of NTZ. Our protocol was insufficient to evaluate PML risk as well as other rare and long-term adverse events such as cancers and other opportunistic infections, which are very important issues in considering the risk/benefit ratio of NTZ. AUTHORS' CONCLUSIONS: Although one trial did not contribute to efficacy results due to its duration, we found robust evidence in favour of a reduction in relapses and disability at 2 years in RRMS patients treated with NTZ. The drug was well tolerated. There are current significant safety concerns due to reporting of an increasing number of PML cases in patients treated with NTZ. This review was unable to provide an up-to-date systematic assessment of the risk due to the maximum 2 year-duration of the trials included. An independent systematic review of the safety profile of NTZ is warranted. NTZ should be used only by skilled neurologists in MS centres under surveillance programs.All the data in this review came from trials supported by the Pharmaceutical Industry. In agreement with the Cochrane Collaboration policy, this may be considered a potential source of bias. PMID- 21975774 TI - Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for adults with early (stage 1 to 3) non-diabetic chronic kidney disease. AB - BACKGROUND: Chronic kidney disease (CKD) is a long term condition that occurs as a result of damage to the kidneys. Early recognition of CKD is becoming increasingly common due to widespread laboratory estimated glomerular filtration rate (eGFR) reporting, raised clinical awareness, and international adoption of Kidney Disease Outcomes Quality Initiative (K/DOQI) classification. Early recognition and management of CKD affords the opportunity not only to prepare for progressive kidney impairment and impending renal replacement therapy, but also for intervening to reduce the risk of progression and cardiovascular disease. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are two classes of antihypertensive drugs that act on the renin-angiotensin aldosterone system. Beneficial effects of ACEi and ARB on renal outcomes and survival in people with a wide range of severity of renal impairment have been reported; however, their effectiveness in the subgroup of people with early CKD (stage 1 to 3) is less certain. OBJECTIVES: This review aimed to evaluate the benefits and harms of ACEi and ARB or both in the management of people with early (stage 1 to 3) CKD who do not have diabetes mellitus. SEARCH STRATEGY: In March 2010 we searched The Cochrane Library, including The Cochrane Renal Group's specialised register and The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. Reference lists of review articles and relevant studies were also checked. The search was conducted using the optimally sensitive strategy developed by the Cochrane Collaboration for the identification of randomised controlled trials (RCTs) with input from an expert in trial search strategy. SELECTION CRITERIA: All RCTs reporting the effect of ACEi or ARB in people with early (stage 1 to 3) CKD who did not have diabetes mellitus were selected for inclusion. Only studies of at least four weeks duration were selected. Authors, working in teams of two, independently assessed the retrieved titles and abstracts, and whenever necessary the full text of these studies were screened to determine which studies satisfied the inclusion criteria. DATA COLLECTION AND ANALYSIS: Data extraction was carried out by two authors, independently, using a standard data extraction form and cross checked by two other authors. Methodological quality of included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross checked by another author. When more than one study reported similar outcomes, data were pooled using the random-effects model, but a fixed-effect model was also analysed to ensure the robustness of the model chosen and to check susceptibility to outliers. Heterogeneity was analysed using a Chi2 test on N-1 degrees of freedom, with an alpha of 0.05 used for statistical significance and with the I2 test. Where data permitted, subgroup analysis was used to explore possible sources of heterogeneity. The quality of the evidence was analysed. MAIN RESULTS: Four RCTs enrolling 2177 participants met our inclusion criteria. Of these, three compared ACEi with placebo and one compared ACEi with ARB. Two studies had an overall low risk of bias, and the other two were considered to be at moderate to high risk of bias. Low to moderate quality of evidence (from two studies representing 1906 patients) suggested that ACEi had no impact on all cause mortality (RR 1.80, 95% CI 0.17 to 19.27, P = 0.63) or cardiovascular events (RR 0.87, 95% CI 0.66 to 1.14, P = 0.31) in people with stage 3 CKD. For all-cause mortality, there was substantial heterogeneity in the results. One study (quality assessment: low risk of bias) reported no difference in the risk of end-stage kidney disease in those with an eGFR > 45 mL/min/1.74 m2 treated with ACEi versus placebo (RR 1.00, 95% CI 0.09 to 1.11, P = 0.99). The (high risk of bias) study that compared ACEi with ARB reported little difference in effect between the treatments when urinary protein, blood pressure or creatinine clearance were compared. No published studies comparing ARB with placebo or ACEi and ARB with placebo were identified. AUTHORS' CONCLUSIONS: Our review demonstrated that there is currently insufficient evidence to determine the effectiveness of ACEi or ARB in patients with stage 1 to 3 CKD who do not have diabetes mellitus. We have identified an area of significant uncertainty for a group of patients who account for most of those labelled as having CKD. PMID- 21975775 TI - Epidermal growth factor receptor blockers for the treatment of ovarian cancer. AB - BACKGROUND: Ovarian cancer is the seventh most common cause of cancer death in women world-wide. Treatment consists of a combination of surgical debulking and platinum-based chemotherapy, alone or in combination with paclitaxel. Between 55% and 75% of women who respond to first-line therapy relapse within two years of completing treatment. Second-line chemotherapy is palliative and aims to reduce symptoms and prolong survival. Increased understanding about the molecular basis of ovarian cancer has led to the development of novel agents, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, and their effectiveness and toxicities in women with advanced ovarian cancer needs to be assessed. OBJECTIVES: To compare the effectiveness and toxicities of epidermal growth factor receptor (EGFR) inhibitors alone or in combination with standard chemotherapy in the treatment of ovarian cancer. SEARCH STRATEGY: We searched the Cochrane Gynaecological Cancer Group Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) Issue 4, 2010, MEDLINE and EMBASE up to October 2010. We also searched registers of clinical trials, abstracts of scientific meetings, and reference lists of included studies, and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing anti-EGFR agents with or without conventional chemotherapy versus conventional chemotherapy alone or no treatment in women with histologically proven ovarian cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risk of bias. We reported adjusted hazard ratios (HRs) for overall and progression-free survival and risk ratios (RRs) comparing adverse events in women who received gemcitabine plus pertuzumab and gemcitabine plus placebo. MAIN RESULTS: We found only one completed and three ongoing RCTs that met our inclusion criteria. The completed trial randomised 131 women with relapsed ovarian cancer to receive gemcitabine and pertuzumab or placebo and gemcitabine (control). There was no statistically significant difference in overall survival (OS), progression-free survival (PFS) and response between women who received gemcitabine and pertuzumab and those who received control, although PFS approached borderline significance (adjusted HR = 0.66, 95% CI 0.43 to 1.03; P = 0.06). The trial reported a higher rate of adverse events in the gemcitabine and pertuzumab arm for most outcomes, but most were not statistically significant (although many approached borderline significance) because the trial lacked statistical power due to its relatively small size and the low number of observed events. The trial was at moderate risk of bias. AUTHORS' CONCLUSIONS: EGFR inhibitors, including pertuzumab, may add activity to conventional chemotherapy for treatment of platinum-resistant ovarian cancer. Certain subsets of women with particularly aggressive tumours resistant to conventional chemotherapy may benefit from EGFR inhibitor treatment. Further RCTs are necessary before EGFR inhibitors are introduced as first- or second-line treatment of ovarian cancer. PMID- 21975776 TI - Repetitive transcranial magnetic stimulation for tinnitus. AB - BACKGROUND: Tinnitus is the perception of sound, in the ear or in the head, in the absence of any external acoustic stimulation. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive means of inducing electrical currents in the brain, and has received increasing attention in recent years for the treatment of many neuropsychiatric disorders, including tinnitus. OBJECTIVES: To assess the effectiveness and safety of rTMS versus placebo in patients with tinnitus. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 24 May 2011. SELECTION CRITERIA: Randomised controlled trials of rTMS versus sham rTMS. DATA COLLECTION AND ANALYSIS: Two review authors reviewed the titles, abstracts and keywords of all records retrieved. Three review authors independently collected and extracted data, and assessed the risk of bias of the trials. MAIN RESULTS: Five trials comprising of 233 participants met our inclusion criteria. Each study described the use of a different rTMS device that delivered different waveforms at different frequencies. All five trials were relatively small studies but generally they demonstrated a low risk of bias.When considering the impact of tinnitus on patients' quality of life, the results of only one study demonstrated a statistically significant improvement in Tinnitus Handicap Inventory (THI) scores at four months follow-up (defined as a 'partial improvement' by the study authors (THI reduction of 21% to 80%)) when low-frequency rTMS was compared with a sham control treatment. However, no statistically significant improvement was demonstrated by another two studies that considered rTMS at the same frequency. Furthermore, this single positive finding should be taken in the context of the many different variables which were recorded at many different points in time by the study authors.In accordance with our pre-specified subgroup analysis we extracted the data from one study to consider the differential effectiveness between 'lower' low-frequency rTMS (1 Hz) and 'higher' low-frequency rTMS (10 Hz, 25 Hz). In doing this we were able to demonstrate a statistically significant difference between rTMS employing a frequency of 1 Hz and the sham group when considering tinnitus severity and disability after four months follow-up ('partial' improvement). However, no statistically significant difference was demonstrated between 10 Hz and 25 Hz rTMS, and the sham control group, when considering the severity and disability of tinnitus at four months follow-up.When considering tinnitus loudness in patients undergoing rTMS we were able to demonstrate a statistically significant reduction in tinnitus loudness when the results of two studies were pooled (risk ratio 4.17, 95% confidence interval 1.30 to 13.40). However, this finding was based on two small trials and consequently the confidence interval was particularly wide.No serious adverse effects were reported in any of the trials. AUTHORS' CONCLUSIONS: There is very limited support for the use of low-frequency rTMS for the treatment of patients with tinnitus. When considering the impact of tinnitus on patients' quality of life, support is from a single study with a low risk of bias based on a single outcome measure at a single point in time. When considering the impact on tinnitus loudness, this is based on the analysis of pooled data with a large confidence interval.Studies suggest that rTMS is a safe treatment for tinnitus in the short term, however there were insufficient data to provide any support for the safety of this treatment in the long-term.More prospective, randomised, placebo controlled, double-blind studies with large sample sizes are needed to confirm the effectiveness of rTMS for tinnitus patients. Uniform, validated, tinnitus specific questionnaires and measurement scales should be used in future studies. PMID- 21975777 TI - Transtheoretical model for dietary and physical exercise modification in weight loss management for overweight and obese adults. AB - BACKGROUND: Obesity is a global public health threat. The transtheoretical model stages of change (TTM SOC) model has long been considered a useful interventional approach in lifestyle modification programmes, but its effectiveness in producing sustainable weight loss in overweight and obese individuals has been found to vary considerably. OBJECTIVES: To assess the effectiveness of dietary and physical activity interventions based on the transtheoretical model, to produce sustainable weight loss in overweight and obese adults. SEARCH STRATEGY: Studies were obtained from searches of multiple electronic bibliographic databases. Date of last search for The Cochrane Library was issue 10, 2010, for MEDLINE Dezember 2010, for EMBASE January 2011 and for PSYCHINFO Januar 2011. SELECTION CRITERIA: Trials were included if they fulfilled the following criteria: randomised controlled clinical trials using TTM SOC as a model, theoretical framework or guideline in designing lifestyle modification strategies, mainly dietary and physical exercise versus a comparison intervention of usual care; one of the outcome measures of the study was weight loss; and participants were overweight or obese adults. DATA COLLECTION AND ANALYSIS: Two researchers independently applied the inclusion criteria to the identified studies and assessed risk of bias. Disagreement was resolved by discussion or by intervention of a third party. Descriptive analysis was conducted for the review. MAIN RESULTS: A total of five studies met the inclusion criteria and a total of 3910 participants were evaluated. The total number of participants randomised to intervention groups was 1834 and 2076 were randomised to control groups. Overall risk of bias was high. The trials varied in length of intervention from six weeks to 24 months, with a median length of nine months. The intervention was found to have limited impact on weight loss (about 2 kg or less) and other outcome measures. There was no conclusive evidence for sustainable weight loss. However, TTM SOC and a combination of physical activity, diet and other interventions tended to produce significant outcomes (particularly change in physical activity and dietary intake). TTM SOC was used inconsistently as a theoretical framework for intervention in the trials. Death and weight gain are the two adverse events reported by the included trials. None of the trials reported health-related quality of life, morbidity, and costs as outcomes. AUTHORS' CONCLUSIONS: TTM SOC and a combination of physical activity, diet and other interventions resulted in minimal weight loss, and there was no conclusive evidence for sustainable weight loss. The impact of TTM SOC as theoretical framework in weight loss management may depend on how it is used as a framework for intervention and in combination with other strategies like diet and physical activities. PMID- 21975778 TI - Non-pharmacological interventions for caregivers of stroke survivors. AB - BACKGROUND: A substantial component of care is provided to stroke survivors by informal caregivers. However, providing such care is often a new and challenging experience and has been linked to a number of adverse outcomes. A range of interventions targeted towards stroke survivors and their family or other informal caregivers have been tested in randomised controlled trials (RCTs). OBJECTIVES: To evaluate the effect of interventions targeted towards informal caregivers of stroke survivors or targeted towards informal caregivers and the care recipient (the stroke survivor). SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (March 2011), CENTRAL (The Cochrane Library Issue 2010, Issue 4), MEDLINE (1950 to August 2010), EMBASE (1980 to December 2010), CINAHL (1982 to August 2010), AMED (1985 to August 2010), PsycINFO (1967 to August 2010) and 11 additional databases. In an effort to identify further published, unpublished and ongoing studies, we searched conference proceedings and trials registers, scanned reference lists of relevant articles and contacted authors and researchers. There were no language restrictions. SELECTION CRITERIA: We included RCTs if they evaluated the effect of non-pharmacological interventions (compared with no care or routine care) on informal caregivers of stroke survivors. We included trials of interventions delivered to stroke survivors and informal caregivers only if the stroke survivor and informal caregiver were randomised as a dyad. We excluded studies which included stroke survivors and caregivers if the stroke survivors were the primary target of the intervention. DATA COLLECTION AND ANALYSIS: Two review authors selected studies for inclusion, independently extracted data and assessed methodological quality. We sought original data from trialists. We categorised interventions into three groups: support and information, teaching procedural knowledge/vocational training type interventions, and psycho-educational type interventions. The primary outcome was caregivers' stress or strain. We resolved disagreements by consensus. MAIN RESULTS: Eight studies, including a total of 1007 participants, met our inclusion criteria. We did not pool the results of all the studies because of substantial methodological, statistical and clinical heterogeneity. For caregivers' stress or strain we found no significant results within categories of intervention, with the exception of one single-centre study examining the effects of a 'vocational training' type intervention which found a mean difference between the intervention and comparator group at the end of scheduled follow-up of -8.67 (95% confidence interval -11.30 to -6.04, P < 0.001) in favour of the 'teaching procedural knowledge' type intervention group. AUTHORS' CONCLUSIONS: It was not possible to carry out a meta-analysis of the evidence from RCTs because of methodological, clinical and statistical heterogeneity. One limitation across all studies was the lack of a description of important characteristics that define the informal caregiver population. However, 'vocational educational' type interventions delivered to caregivers prior to the stroke survivor's discharge from hospital appear to be the most promising intervention. However, this is based on the results from one, small, single centre study. PMID- 21975779 TI - Interventions for visual field defects in patients with stroke. AB - BACKGROUND: Visual field defects are estimated to affect 20% to 57% of people who have had a stroke. Visual field defects can affect functional ability in activities of daily living (commonly affecting mobility, reading and driving), quality of life, ability to participate in rehabilitation, and depression, anxiety and social isolation following stroke. There are many interventions for visual field defects, which are proposed to work by restoring the visual field (restitution); compensating for the visual field defect by changing behaviour or activity (compensation); substituting for the visual field defect by using a device or extraneous modification (substitution); or ensuring appropriate diagnosis, referral and treatment prescription through standardised assessment or screening, or both. OBJECTIVES: To determine the effects of interventions for people with visual field defects after stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (February 2011), the Cochrane Eyes and Vision Group Trials Register (December 2009) and nine electronic bibliographic databases including CENTRAL (The Cochrane Library 2009, Issue 4), MEDLINE (1950 to December 2009), EMBASE (1980 to December 2009), CINAHL (1982 to December 2009), AMED (1985 to December 2009), and PsycINFO (1967 to December 2009). We also searched reference lists and trials registers, handsearched journals and conference proceedings and contacted experts. SELECTION CRITERIA: Randomised trials in adults after stroke, where the intervention was specifically targeted at improving the visual field defect or improving the ability of the participant to cope with the visual field loss. The primary outcome was functional ability in activities of daily living and secondary outcomes included functional ability in extended activities of daily living, reading ability, visual field measures, balance, falls, depression and anxiety, discharge destination or residence after stroke, quality of life and social isolation, visual scanning, adverse events and death. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts, extracted data and appraised trials. We undertook an assessment of methodological quality for allocation concealment, blinding of outcome assessors, method of dealing with missing data, and other potential sources of bias. MAIN RESULTS: Thirteen studies (344 randomised participants, 285 of whom were participants with stroke) met the inclusion criteria for this review. However, only six of these studies compared the effect of an intervention with a placebo, control or no treatment group and were included in comparisons within this review. Four studies compared the effect of scanning (compensatory) training with a control or placebo intervention. Meta-analysis demonstrated that scanning training is more effective than control or placebo at improving reading ability (three studies, 129 participants; mean difference (MD) 3.24, 95% confidence interval (CI) 0.84 to 5.59) and visual scanning (three studies, 129 participants; MD 18.84, 95% CI 12.01 to 25.66) but that scanning may not improve visual field outcomes (two studies, 110 participants; MD -0.70, 95% CI -2.28 to 0.88). There were insufficient data to enable generalised conclusions to be made about the effectiveness of scanning training relative to control or placebo for the primary outcome of activities of daily living (one study, 33 participants). Only one study (19 participants) compared the effect of a restitutive intervention with a control or placebo intervention and only one study (39 participants) compared the effect of a substitutive intervention with a control or placebo intervention. AUTHORS' CONCLUSIONS: There is limited evidence which supports the use of compensatory scanning training for patients with visual field defects (and possibly co-existing visual neglect) to improve scanning and reading outcomes. There is insufficient evidence to reach a conclusion about the impact of compensatory scanning training on functional activities of daily living. There is insufficient evidence to reach generalised conclusions about the benefits of visual restitution training (VRT) (restitutive intervention) or prisms (substitutive intervention) for patients with visual field defects after stroke. PMID- 21975780 TI - Interventions for disorders of eye movement in patients with stroke. AB - BACKGROUND: Eye movement disorders may affect over 70% of stroke patients. These eye movement disorders can result in difficulty maintaining the normal ocular position and difficulty moving the eyes appropriately. The resulting functional disabilities include a loss of depth perception, reduced hand-to-eye co ordination, marked difficulties with near tasks and reading and reduced ability to scan the visual environment. They can also impact on the effectiveness of rehabilitation therapy. There are a wide variety of different treatment interventions proposed for eye movement disorders after stroke. However, in the past, there has been a lack of evidence specific to the impact of interventions on the functional outcome of patients with stroke. OBJECTIVES: To determine the effects of interventions for eye movement disorders on functional ability following stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (February 2011), the Cochrane Eyes and Vision Group Trials Register (December 2009) and nine electronic bibliographic databases including CENTRAL (The Cochrane Library 2009, Issue 4), MEDLINE (1950 to December 2009), EMBASE (1980 to December 2009), CINAHL (1982 to December 2009), AMED (1985 to December 2009), and PsycINFO (1967 to December 2009). We also searched reference lists and trials registers, handsearched journals and conference proceedings, and contacted experts. SELECTION CRITERIA: Randomised trials in adults after stroke where the intervention was specifically targeted at improving the eye movement disorder or improving the ability of the participant to cope with the eye movement disorder. The primary outcome was functional ability in activities of daily living. Secondary outcomes included functional ability in extended activities of daily living, eye movement measures, balance, falls, depression or anxiety, discharge destination or residence after stroke, quality of life and social isolation, adverse events, and death. DATA COLLECTION AND ANALYSIS: Two authors independently screened abstracts, extracted data and appraised trials. We undertook assessment of methodological quality for allocation concealment, blinding of outcome assessor, method of dealing with missing data, and other potential sources of bias. MAIN RESULTS: Two studies (28 participants but only five were people with stroke) met the inclusion criteria and were included in this review. Both studies investigated pharmacological interventions for disorders of eye movement in patients with stroke. It was not appropriate to pool data and we were not able to draw conclusions from these studies. We found no other randomised studies which investigated interventions for disorders of eye movement in patients with stroke. AUTHORS' CONCLUSIONS: There is insufficient evidence to reach conclusions about the effectiveness of interventions for patients with eye movement disorders after stroke. High quality research in the form of well-designed randomised trials are urgently required. PMID- 21975781 TI - Sweet tasting solutions for reduction of needle-related procedural pain in children aged one to 16 years. AB - BACKGROUND: Large numbers of studies have shown that oral sucrose or glucose, with or without non-nutritive sucking given prior to painful procedures result in a significant reduction in behavioral pain responses during or following painful procedures compared with placebo, no treatment or non-nutritive sucking alone, in newborns and infants up to 12 months of age. It is not known if these pain reducing effects exist for older infants and children one year to 16 years of age. OBJECTIVES: To determine the efficacy of sweet tasting solutions or substances for reducing needle-related procedural pain in children beyond one year of age. SEARCH STRATEGY: We searched the following databases: the Cochrane Register of Controlled Trials (CCTR), MEDLINE, EMBASE, PsycINFO, ACP Journal Club, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), Cochrane Methodology Register, Health Technology Assessment, and the NHS Economic Evaluation Database, and on the EBSCOhost interface: CINAHL. We applied no language or document type restrictions. We used the standard methods of The Cochrane Collaboration. The last date of the search was June 30, 2011. SELECTION CRITERIA: Randomized controlled trials (RCTs) in which children from one year up to 16 years of age, received a sweet tasting solution or substance for needle-related procedural pain. Control conditions included water, non-sweet tasting substances, pacifier, distraction, no treatment, positioning/containment or breastfeeding. DATA COLLECTION AND ANALYSIS: Outcome measures included composite pain scores, physiological or behavioral pain indicators, self-report of pain or parental- or healthcare professional-report of child's pain. We reported mean differences (MD) with 95% confidence intervals (CI) using fixed-effect or random-effects models as appropriate for continuous outcome measures. We planned to report risk ratio (RR) and risk difference (RD) for dichotomous outcomes. We used the Chi(2) test and I(2) statistic to assess between-study heterogeneity. MAIN RESULTS: We included four studies (330 participants). Two studies focused on toddlers and pre-school children receiving sucrose for immunization pain compared with water or no treatment and two studies included school-aged children receiving sweet or unsweetened chewing gum before, or, before and during immunization and blood collection. Results for the toddlers/pre-school children were conflicting. Participants in the sucrose group in one study had significantly lower cry duration and behavioral pain scores, compared with the no intervention group, while crying time did not differ between the sucrose and the no intervention group in the other study. For school-aged children, chewing sweet gum either before, or during the procedure, did not significantly reduce pain scores. AUTHORS' CONCLUSIONS: Based on these four studies, two of which were subgroups of small numbers of eligible toddlers from larger studies, there is insufficient evidence of the analgesic effects of sweet tasting solutions or substances during acute painful procedures in children over one year of age. Further well-conducted RCTs are warranted in this population. PMID- 21975782 TI - Angioplasty versus stenting for subclavian artery stenosis. AB - BACKGROUND: There is insufficient evidence to guide stent usage following angioplasty in subclavian artery stenosis. OBJECTIVES: The aim of this review was to determine whether stenting is more effective than angioplasty alone for stenosis of the subclavian artery. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched August 2011) and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3). In addition, the authors searched the MEDLINE, EMBASE and LILACS databases, and handsearched relevant journals. Informal enquiries were made with the major stent device manufacturers to obtain information on unpublished data and any ongoing trials. There was no restriction on language. SELECTION CRITERIA: Randomized controlled trials of endovascular treatment of subclavian artery lesions comparing angioplasty alone and stent implantation. DATA COLLECTION AND ANALYSIS: Two authors independently evaluated studies to assess eligibility. Discrepancies were resolved by discussion. If there was no agreement, the third author was asked to assess the study for inclusion. MAIN RESULTS: To date we have not identified any completed or ongoing randomized controlled trials comparing percutaneous transluminal angioplasty and stenting for subclavian artery stenosis. AUTHORS' CONCLUSIONS: There is currently insufficient evidence to determine whether stenting is more effective than angioplasty alone for stenosis of the subclavian artery. PMID- 21975783 TI - Home-based educational interventions for children with asthma. AB - BACKGROUND: While guidelines recommend that children with asthma should receive asthma education, it is not known if education delivered in the home is superior to usual care or the same education delivered elsewhere. The home setting allows educators to reach populations (such as the economically disadvantaged) that may experience barriers to care (such as lack of transportation) within a familiar environment. OBJECTIVES: To perform a systematic review on educational interventions for asthma delivered in the home to children, caregivers or both, and to determine the effects of such interventions on asthma-related health outcomes. We also planned to make the education interventions accessible to readers by summarising the content and components. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register of trials, which includes the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED and PsycINFO, and handsearched respiratory journals and meeting abstracts. We also searched the Education Resources Information Center database (ERIC), reference lists of trials and review articles (last search January 2011). SELECTION CRITERIA: We included randomised controlled trials of asthma education delivered in the home to children, their caregivers or both. In the first comparison, eligible control groups were provided usual care or the same education delivered outside of the home. For the second comparison, control groups received a less intensive educational intervention delivered in the home. DATA COLLECTION AND ANALYSIS: Two authors independently selected the trials, assessed trial quality and extracted the data. We contacted study authors for additional information. We pooled dichotomous data with fixed-effect odds ratio and continuous data with mean difference (MD) using a fixed-effect where possible. MAIN RESULTS: A total of 12 studies involving 2342 children were included. Eleven out of 12 trials were conducted in North America, within urban or suburban settings involving vulnerable populations. The studies were overall of good methodological quality. They differed markedly in terms of age, severity of asthma, context and content of the educational intervention leading to substantial clinical heterogeneity. Due to this clinical heterogeneity, we did not pool results for our primary outcome, the number of patients with exacerbations requiring emergency department (ED) visit. The mean number of exacerbations requiring ED visits per person at six months was not significantly different between the home-based intervention and control groups (N = 2 studies; MD 0.04; 95% confidence interval (CI) -0.20 to 0.27). Only one trial contributed to our other primary outcome, exacerbations requiring a course of oral corticosteroids. Hospital admissions also demonstrated wide variation between trials with significant changes in some trials in both directions. Quality of life improved in both education and control groups over time.A table summarising some of the key components of the education programmes is included in the review. AUTHORS' CONCLUSIONS: We found inconsistent evidence for home-based asthma educational interventions compared to standard care, education delivered outside of the home or a less intensive educational intervention delivered at home. Although education remains a key component of managing asthma in children, advocated in numerous guidelines, this review does not contribute further information on the fundamental content and optimum setting for such educational interventions. PMID- 21975784 TI - Statins for women with polycystic ovary syndrome not actively trying to conceive. AB - BACKGROUND: Statins, as lipid-lowering agents with pleiotropic actions, are likely not only to improve the dyslipidaemia associated with polycystic ovary syndrome but may also exert other beneficial metabolic and endocrine effects. OBJECTIVES: To assess the efficacy and safety of statin therapy for women with polycystic ovary syndrome (PCOS) who are not actively trying to conceive. SEARCH STRATEGY: We searched the following databases (from inception to week 1, July 2011): the Cochrane Menstrual Disorders and Subfertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and CINAHL. We handsearched relevant conference proceedings and references of the identified articles for additional studies. We also contacted experts for further studies in progress. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing a statin versus placebo or statin in combination with another drug versus another drug alone in women with PCOS. DATA COLLECTION AND ANALYSIS: Two review authors performed data collection and analysis independently. MAIN RESULTS: Four trials fulfilled the criteria for inclusion. They comprised a total of 244 women with PCOS receiving 12 weeks or 6 weeks of treatment. Two trials (184 women randomised) studied the effects of simvastatin and two trials (60 women randomised) studied the effects of atorvastatin. There was no good evidence that statins improved menstrual regularity, spontaneous ovulation rate, hirsutism or acne, either alone or in combination with the combined oral contraceptive pill (OCP). Nor were there any significant effects on body mass index (BMI). Statins were effective in lowering testosterone levels (nmol/L) (mean difference (MD) -0.90, 95% CI -1.18 to -0.62, P < 0.00001, 3 RCTs, 105 women) when used alone or with the OCP. Statins also improved total cholesterol, low-density lipoprotein (LDL) and triglycerides but had no significant effect on high-density lipoprotein (HDL) levels, high sensitivity (HS) C-reactive protein (HS-CRP), fasting insulin or homeostatic model assessment (HOMA) insulin resistance. No serious adverse events were reported in any of the included studies. AUTHORS' CONCLUSIONS: Although statins improve lipid profiles and reduce testosterone levels in women with PCOS, there is no evidence that statins improve resumption of menstrual regularity or spontaneous ovulation, nor is there any improvement of hirsutism or acne. There is a need for further research to be performed with large sample sizes and well designed RCTs to assess clinical outcomes. PMID- 21975785 TI - Hematopoietic stem cell transplantation for people with beta-thalassaemia major. AB - BACKGROUND: Thalassemia is an inherited blood disorder, caused by mutations in regulatory genes and transmitted as an autosomal recessive disorder, which results in a reduced rate of synthesis of one of the globin chains that make up haemoglobin. In beta-thalassaemia major there is an underproduction of beta globin chains combined with excess of free alpha-globin chains. The excess free alpha-globin chains damage the red blood cell membranes, leading to their destruction and a phenomenon termed ineffective erythropoiesis. The conventional approach to treatment is based on the correction of haemoglobin status through regular blood transfusions and iron chelation therapy for iron overload. Although conventional treatment has the capacity to improve the quality of life of people with beta-thalassaemia major, allogeneic hematopoietic stem cell transplantation is the only currently available procedure which has the potential to definitively cure the disease. OBJECTIVES: To evaluate the effectiveness and safety of different types of allogeneic hematopoietic stem cell transplantation, in people with severe transfusion-dependant beta-thalassaemia major, beta-thalassaemia intermedia or beta0/+- thalassaemia variants requiring chronic blood transfusion. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 27 May 2011. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials comparing allogeneic hematopoietic stem cell transplantation with each other or with standard therapy (regular transfusion and chelation regimen). DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies and had planned to extract data and assess risk of bias using standard Cochrane Collaboration methodologies but no studies were identified for inclusion. MAIN RESULTS: No relevant studies were retrieved after a comprehensive search of the literature. AUTHORS' CONCLUSIONS: We were unable to identify any randomised controlled trials or quasi-randomised controlled trials on the effectiveness and safety of different types of allogeneic stem cell transplantation in people with severe transfusion-dependant beta-thalassaemia major or beta0/+- thalassaemia variants requiring chronic blood transfusion. The absence of high-level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately-powered, randomised controlled clinical trials. PMID- 21975786 TI - Allogeneic hematopoietic cell transplantation for adult acute lymphoblastic leukemia (ALL) in first complete remission. AB - BACKGROUND: Consolidation chemotherapy, autologous hematopoietic cell transplantation (HCT) and allogeneic HCT represent potential treatment alternatives for post-remission therapy in adult acute lymphoblastic leukemia (ALL), but there is genuine uncertainty regarding the optimal approach. OBJECTIVES: To assess the effect of matched sibling donor vs. no donor status for adults with ALL in first complete remission (CR1). SEARCH STRATEGY: We performed a search of CENTRAL, MEDLINE and EMBASE electronic databases in September 2010 along with handsearching of literature cited in relevant primary articles, search of abstracts from American Society of Hematology and American Society of Clinical Oncology meetings, as well as consultation with content experts in the field. SELECTION CRITERIA: Review was performed by two authors, and Inclusion criteria included the following: controlled trials with donor vs. no donor comparison with assignment by genetic randomizationin adults with ALL in CR1. DATA COLLECTION AND ANALYSIS: We extracted data on benefits (overall survival, progression-free survival) and harms (treatment-related mortality, relapse) of compared treatments. Adverse events were considered, but analysis of individual adverse events was not possible from the reported literature. We pooled summary results from each study using a random-effects model. We assessed heterogeneity. We performed subgroup analyses for disease risk categories. We performed sensitivity analyses according to methodological quality. MAIN RESULTS: A total of 14 relevant trials were identified, consisting of a total of 3157 patients. There was a statistically significant overall survival advantage in favor of the donor versus no donor group (HR 0.86; 95% CI 0.77 to 0.97; P = 0.01), as well as significant improvement in disease-free survival in the donor group(HR 0.82; 95% CI 0.72 to 0.94; P = 0.004). Those in the donor group had significant reduction in primary disease relapse(RR 0.53; 95% CI 0.37 to 0.76; P = 0.0004) and significant increase in non-relapse mortality(RR 2.8; 95% CI 1.66 to 4.73; P = 0.001). Significant heterogeneity was detected in analysis of relapse (Chi(2) 40.51, df = 6, P < 0.00001; I(2) = 85%). In regard to methodologic quality, the majority of included studies were free of selective reporting, and performed analyses according to intention to treat. Conversely, few reported sample size calculation that informed the study design. While blinding was considered as an important domain of methodological quality, none of the studies reported on whether any of the study personnel were blinded (e.g. subjects, personnel, outcome assessors, data analysts etc). Therefore, we did not consider blinding further in the analysis of methodological quality in this review. AUTHORS' CONCLUSIONS: The results of this systematic review and meta-analysis support matched sibling donor allogeneic hematopoietic cell transplantation as the optimal post-remission therapy in ALL patients aged 15 years or over. This therapy offers superior overall survival and disease-free survival, and significantly reduces the risk of disease relapse, but does impose an increased risk of non-relapse mortality. Importantly these data are based on adult ALL treated with largely total body irradiation-based myeloablative conditioning and sibling donor transplantation and, therefore, cannot be generalized to pediatric ALL, alternative donors including HLA (human leukocyte antigen) mismatched or unrelated donors, or reduced toxicity or non-myeloablative conditioning regimens. PMID- 21975787 TI - Pharmacologic treatment for memory disorder in multiple sclerosis. AB - BACKGROUND: Memory disorder is one of the most frequent cognitive impairment and has a great negative impact on the quality of life in patients with multiple sclerosis (MS). A few pharmacologic agents appear to be effective to memory disorder in patients with MS in some existing randomised controlled trials. OBJECTIVES: To assess the absolute and comparative efficacy, tolerability and safety of pharmacologic treatments for memory disorder in adult patients with MS. SEARCH STRATEGY: We searched the Cochrane Multiple Sclerosis Group's Trials Register (17 January 2011), PsycINFO (January 1980 - April Week 4 2011) and CBMdisc (January 1978 - 6 April 2011), and checked reference lists of identified articles, searched some relevant journals manually, registers of clinical trials and published abstracts of conference proceedings. SELECTION CRITERIA: All double blind, randomized controlled parallel trials on pharmacologic treatment versus placebo treatment or no treatment or one or more pharmacologic treatments, without restrictions regarding dose, route of administration and frequency, administration duration>=12 weeks for memory disorder in adult patients with MS who display at least mild memory impairment at 0.5 standard deviations below age and-sex-based normative data on a validated memory scale. Adequately randomized or quasi-randomized trials were included. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Disagreements were discussed and resolved by consensus among review authors. Principal investigators of included studies were contacted for additional data or confirmation. MAIN RESULTS: Four RCTs involving adult patients with all the types of MS and at least mild memory impairment were included, evaluating donepezil, Ginkgo biloba (GB), memantine and rivastigmine respectively vs placebo in treating memory disorder in MS.There were no serious adverse events in intervention groups.The quality of the included studies was overall low, some of important variables were not matched between groups at baseline, the samples of subjects were relatively small and the follow-up was short. Three RCTs which evaluate GB, memantine, rivastigmine respectively vs placebo are currently ongoing. AUTHORS' CONCLUSIONS: Until the results of ongoing studies are available, there is no convincing evidence to support pharmacologic intervention as an effective treatment for memory disorder in MS patients. However, donepezil, Ginkgo biloba, memantine and rivastigmine resulted to be safe and well tolerated as adverse events such as nausea, diarrhea, somnolence, and constipation were not frequent, while no serious adverse effects were reported. Future high quality randomised controlled trials are needed. PMID- 21975788 TI - Combination therapy for pain management in inflammatory arthritis (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis). AB - BACKGROUND: Despite optimal therapy with disease-modifying antirheumatic drugs, many people with inflammatory arthritis (IA) continue to have persistent pain that may require additional therapy. OBJECTIVES: To assess the benefits and safety of combination pain therapy for people with IA (rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA) and other spondyloarthritis (SpA)). We planned to assess differences in effects between patients on background disease-modifying antirheumatic drug (DMARD) therapy and patients on no background therapy in subgroup analyses. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); MEDLINE; and EMBASE. We did not impose any date or language restrictions in the search. We also handsearched conference proceedings of the American College of Rheumatology and the European League against Rheumatism (2008 10). SELECTION CRITERIA: Randomised and controlled clinical trials (RCTs and CCTs) assessing combination therapy (at least two drugs from the following classes: analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, opioid-like drugs and neuromodulators (antidepressants, anticonvulsants and muscle relaxants)) compared with monotherapy, for adults with IA (RA, AS, PsA and other SpA). We speficically excluded studies that did not report pain or studies without a standardised pain scale as an outcome measure. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, assessed risk of bias and extracted data. MAIN RESULTS: Twenty-three trials (total of 912 patients) met the inclusion criteria (22 in RA; one in a mixed population of RA and osteoarthritis); all except one were published before 1990. Most study populations were not taking DMARDs (e.g. methotrexate, sulphasalazine, hydroxychloroquine and leflunomide) and all studies were performed prior to the introduction of biologic therapies (e.g. etanercept, infliximab and adalimumab). All trials were at high risk of bias, heterogeneity precluded meta-analysis, and we were only able to report a general description of results.The majority (18 studies, 78%) found no differences between the combination and monotherapy treatments they studied, while five (22%) reported conflicting results, favouring either the combination or monotherapy arms.From the 12 trials on NSAID + analgesic vs NSAID, nine reported no significant difference between the interventions, while three did: in two, the combination therapy achieved better pain control; and the third trial compared combination therapy with two different dosages of monotherapy (NSAID alone) and reported that a high dose phenylbutazone was superior to combination therapy (paracetamol + aspirin), which was superior to low dose phenylbutazone.From the five studies on the combination of two NSAIDS vs one NSAID, four reported no significant differences between interventions, and one reported significantly better pain control with combination therapy.The single trial comparing a combination of opioid + neuromodulator vs opioid reported better pain control with monotherapy.The remaining trials (NSAID + neuromodulator vs NSAID (3 trials); opioid + NSAID vs NSAID (1 trial); and opioid + analgesic vs analgesic (1 trial)) found no significant difference between combination therapy and monotherapy.Information regarding withdrawals due to inadequate analgesia and safety was incompletely reported, but in general there were no differences between combination therapy and monotherapy.No data were available that addressed the value of combination pain therapy or monotherapy for people with IA who have optimal disease suppression. There were no studies that included patients with AS, PsA or SpA. AUTHORS' CONCLUSIONS: Based on 23 trials, all at high risk of bias, there is insufficient evidence to establish the value of combination therapy over monotherapy for people with IA. Importantly, there are no studies addressing the value of combination therapy for patients with IA who have persistent pain despite optimal disease suppression. Well designed trials are needed to address this question. PMID- 21975789 TI - Pain management for rheumatoid arthritis and cardiovascular or renal comorbidity. AB - BACKGROUND: Pain in rheumatoid arthritis is common, is often multi-factorial and many different pharmacotherapeutic agents are routinely used for pain management. There are concerns that some of the pain pharmacotherapies currently used may increase the risk of adverse events in people with rheumatoid arthritis and concurrent cardiovascular or renal disease. OBJECTIVES: To systematically assess and collate the scientific evidence on the efficacy and safety of using pain pharmacotherapy in people with rheumatoid arthritis and cardiovascular or renal comorbidities. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 4); MEDLINE, from 1950; EMBASE, from 1980; the Cochrane Database of Systematic Reviews (CDSR) and the Database of Abstracts of Reviews of Effects (DARE). We also handsearched the conference proceedings for American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) for 2008-09, and checked the websites of regulatory agencies for reported adverse events, labels and warnings. SELECTION CRITERIA: We considered randomised controlled trials and non-randomised studies comparing the efficacy and safety of pain pharmacotherapies in patients with rheumatoid arthritis, with and without comorbid cardiovascular or renal conditions.In addition, we also considered controlled before-after studies, interrupted time series, cohort and case control studies and case series (N >= 20) to assess safety.For the purpose of our review, pain pharmacotherapy was defined as including simple analgesics (such as paracetamol), non-steroidal anti inflammatory drugs (NSAIDs), opioids or opioid-like drugs (such as tramadol), and neuromodulators (including anti-depressants, anti-convulsants, and muscle relaxants). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the search results and planned to extract data and appraise the risk of bias of included studies. MAIN RESULTS: We did not identify any studies meeting our inclusion criteria. Many of the trials of NSAIDs explicitly excluded patients with cardiovascular or renal comorbidities.We did identify one trial that reported evidence in mixed populations (including both rheumatoid arthritis and osteoarthritis) taking either diclofenac or etoricoxib. In this study, the presence of cardiovascular disease increased the likelihood of a further cardiovascular event three-fold. Patients with two or more cardiovascular comorbidities showed a two-fold increased likelihood of adverse cardiovascular events. AUTHORS' CONCLUSIONS: There were no trials that specifically compared the efficacy and safety of pain pharmacotherapies for patients with rheumatoid arthritis, with and without comorbid cardiovascular or renal conditions.In the absence of specific evidence in rheumatoid arthritis, current guidelines recommend that NSAIDs be used with caution in the general rheumatoid arthritis population while highlighting the added need for extra vigilance in patients with established cardiovascular disease or risk factors for its development. Current guidelines regarding the use of NSAIDs and opioids in moderate to severe renal impairment should also be applied to the rheumatoid arthritis population.Further research is required to guide clinicians when treating pain in rheumatoid arthritis. PMID- 21975790 TI - Luteal phase support for assisted reproduction cycles. AB - BACKGROUND: Progesterone prepares the endometrium for pregnancy by stimulating proliferation in response to human chorionic gonadotropin (hCG), which is produced by the corpus luteum. This occurs in the luteal phase of the menstrual cycle. In assisted reproduction techniques (ART) the progesterone or hCG levels, or both, are low and the natural process is insufficient, so the luteal phase is supported with either progesterone, hCG or gonadotropin releasing hormone (GnRH) agonists. Luteal phase support improves implantation rate and thus pregnancy rates but the ideal method is still unclear. This is an update of a Cochrane Review published in 2004 (Daya 2004). OBJECTIVES: To determine the relative effectiveness and safety of methods of luteal phase support in subfertile women undergoing assisted reproductive technology. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, Database of Abstracts of Reviews of Effects (DARE), LILACS, conference abstracts on the ISI Web of Knowledge, OpenSigle for grey literature from Europe, and ongoing clinical trials registered online. The final search was in February 2011. SELECTION CRITERIA: Randomised controlled trials of luteal phase support in ART investigating progesterone, hCG or GnRH agonist supplementation in in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles. Quasi-randomised trials and trials using frozen transfers or donor oocyte cycles were excluded. DATA COLLECTION AND ANALYSIS: We extracted data per women and three review authors independently assessed risk of bias. We contacted the original authors when data were missing or the risk of bias was unclear. We entered all data in six different comparisons. We calculated the Peto odds ratio (Peto OR) for each comparison. MAIN RESULTS: Sixty-nine studies with a total of 16,327 women were included. We assessed most of the studies as having an unclear risk of bias, which we interpreted as a high risk of bias. Because of the great number of different comparisons, the average number of included studies in a single comparison was only 1.5 for live birth and 6.1 for clinical pregnancy.Five studies (746 women) compared hCG versus placebo or no treatment. There was no evidence of a difference between hCG and placebo or no treatment except for ongoing pregnancy: Peto OR 1.75 (95% CI 1.09 to 2.81), suggesting a benefit from hCG. There was a significantly higher risk of ovarian hyperstimulation syndrome (OHSS) when hCG was used (Peto OR 3.62, 95% CI 1.85 to 7.06).There were eight studies (875 women) in the second comparison, progesterone versus placebo or no treatment. The results suggested a significant effect in favour of progesterone for the live birth rate (Peto OR 2.95, 95% CI 1.02 to 8.56) based on one study. For clinical pregnancy (CPR) the results also suggested a significant result in favour of progesterone (Peto OR 1.83, 95% CI 1.29 to 2.61) based on seven studies. For the other outcomes the results indicated no difference in effect.The third comparison (15 studies, 2117 women) investigated progesterone versus hCG regimens. The hCG regimens were subgrouped into comparisons of progesterone versus hCG and progesterone versus progesterone + hCG. The results did not indicate a difference of effect between the interventions, except for OHSS. Subgroup analysis of progesterone versus progesterone + hCG showed a significant benefit from progesterone (Peto OR 0.45, 95% CI 0.26 to 0.79).The fourth comparison (nine studies, 1571 women) compared progesterone versus progesterone + oestrogen. Outcomes were subgrouped by route of administration. The results for clinical pregnancy rate in the subgroup progesterone versus progesterone + transdermal oestrogen suggested a significant benefit from progesterone + oestrogen. There was no evidence of a difference in effect for other outcomes.Six studies (1646 women) investigated progesterone versus progesterone + GnRH agonist. We subgrouped the studies for single-dose GnRH agonist and multiple-dose GnRH agonist. For the live birth, clinical pregnancy and ongoing pregnancy rate the results suggested a significant effect in favour of progesterone + GnRH agonist. The Peto OR for the live birth rate was 2.44 (95% CI 1.62 to 3.67), for the clinical pregnancy rate was 1.36 (95% CI 1.11 to 1.66) and for the ongoing pregnancy rate was 1.31 (95% CI 1.03 to 1.67). The results for miscarriage and multiple pregnancy did not indicate a difference of effect.The last comparison (32 studies, 9839 women) investigated different progesterone regimens:intramuscular (IM) versus oral administration, IM versus vaginal or rectal administration, vaginal or rectal versus oral administration, low-dose vaginal versus high-dose vaginal progesterone administration, short protocol versus long protocol and micronized progesterone versus synthetic progesterone. The main results of this comparison did not indicate a difference of effect except in some subgroup analyses. For the outcome clinical pregnancy, subgroup analysis of micronized progesterone versus synthetic progesterone showed a significant benefit from synthetic progesterone (Peto OR 0.79, 95% CI 0.65 to 0.96). For the outcome multiple pregnancy, the subgroup analysis of IM progesterone versus oral progesterone suggested a significant benefit from oral progesterone (Peto OR 4.39, 95% CI 1.28 to 15.01). AUTHORS' CONCLUSIONS: This review showed a significant effect in favour of progesterone for luteal phase support, favouring synthetic progesterone over micronized progesterone. Overall, the addition of other substances such as estrogen or hCG did not seem to improve outcomes. We also found no evidence favouring a specific route or duration of administration of progesterone. We found that hCG, or hCG plus progesterone, was associated with a higher risk of OHSS. The use of hCG should therefore be avoided. There were significant results showing a benefit from addition of GnRH agonist to progesterone for the outcomes of live birth, clinical pregnancy and ongoing pregnancy. For now, progesterone seems to be the best option as luteal phase support, with better pregnancy results when synthetic progesterone is used. PMID- 21975791 TI - Valproic acid and sodium valproate for neuropathic pain and fibromyalgia in adults. AB - BACKGROUND: Valproic acid and its sodium salt (sodium valproate) are antiepileptic drugs that are sometimes used to treat chronic neuropathic pain and fibromyalgia, although they are not licensed for this use. OBJECTIVES: To evaluate the analgesic efficacy and adverse effects of valproic acid and sodium valproate in the management of chronic neuropathic pain and fibromyalgia. SEARCH STRATEGY: We identified randomised controlled trials (RCTs) of valproic acid and sodium valproate in acute, and chronic pain by searching MEDLINE, EMBASE and Cochrane CENTRAL to June 2011, together with reference lists of retrieved papers and reviews. SELECTION CRITERIA: RCTs that were double blind and of eight-weeks duration or longer, reporting on analgesic effects and adverse events with valproic acid and sodium valproate in the treatment of chronic neuropathic pain and fibromyalgia. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted results and scored for quality. We extracted efficacy and adverse event data, and examined issues of study quality. MAIN RESULTS: We included three studies, two in diabetic neuropathy (42 participants treated with valproate, 42 with placebo), and one in post-herpetic neuralgia (23 treated with divalproex sodium, 22 with placebo). Study duration was eight or 12 weeks. No studies were found in fibromyalgia.Only one study reported one of our primary outcomes (>= 50% pain relief), while all three reported group means for pain reduction from baseline to endpoint. In all three studies; efficacy results were given only for participants who completed the study. One study in diabetic neuropathy and the study in post-herpetic neuralgia reported significant differences between active and placebo groups, but there were insufficient data for reliable pooled analysis.More adverse events were reported with active treatment than placebo, and included nausea, drowsiness and abnormal liver function tests. One participant taking sodium valproate withdrew due to serious derangement of liver enzymes. AUTHORS' CONCLUSIONS: These three studies no more than hint that sodium valproate may reduce pain in diabetic neuropathy, and divalproex sodium in post herpetic neuralgia, but the use of 'completer' analysis may overestimate efficacy, and there were too few data for pooled analysis of efficacy or harm, or to have confidence in the results of the individual studies. There is insufficient evidence to support the use of valproic acid or sodium valproate as a first-line treatment for neuropathic pain. There is more robust evidence of greater efficacy for a small number of other drugs. PMID- 21975792 TI - If there are no randomised controlled trials, do we always need more research? PMID- 21975793 TI - Post-operative pain management. PMID- 21975794 TI - Centralised access to evidence-informed nutrition actions. PMID- 21975795 TI - Accuracy of fit of 3-to-3 retainers after adhesive fixation using a neodymium iron-boron magnet chain. AB - BACKGROUND AND OBJECTIVE: Six-base retainers are often used to prevent tertiary crowding. To minimize shear stress on the retainer, these should be fitted as precisely as possible. The aim of this study was to compare the accuracy of fit of 6-base retainers after adhesive fixation using a neodymium-iron-boron (NdFeB) magnet chain or a resin positioning aid. MATERIALS AND METHODS: A 6-base retainer was prepared for 40 pseudo-anonymous lower jaw models (2 * 20). Temporary fixation was performed with a resin positioning aid or a NdFeB magnet chain. The adhesive fixation of the retainers was randomized. The area and vertical distance between wire and teeth were determined by histomorphometry. The results were evaluated by ANOVA. The probability of error was specified as 5%. RESULTS: With the magnetic chain method, the area was significantly smaller than with the positioning aid (p = 0.0125). The difference between the two methods was ca. 1.3 mm2. Moreover, the measured distance was affected significantly by the method used (p < 0.0002). With the magnet chain, the distance between the tooth and retainer was reduced by a mean of 0.05 mm. Conclusion. The fit of the retainer wire improves somewhat when the NdFeB magnet chain is used even though the wire is not as precisely positioned as it would be with a custom-made positioning aid. PMID- 21975796 TI - Omacor and omega-3 fatty acids for treatment of coronary artery disease and the pleiotropic effects. AB - Omega-3 polyunsaturated fatty acids are found in fish oil and they have been shown to mitigate the risk of cardiovascular disease. Omega-3 fatty acids are essential fatty acids because they cannot be synthesized de novo and must be consumed from dietary sources such as marine fish. It reduces fatal and nonfatal myocardial infarction, stroke, coronary artery disease, sudden cardiac death, and all-cause mortality. It also has beneficial effects in mortality reduction after a myocardial infarction. Omacor is a highly potent form of Omega-3 fatty acids that lowers plasma triglycerides. In patients with severe hypertriglyceridemia who are refractory to statins, it helps augment triglyceride reduction. Omacor also increases high-density lipoprotein and decreases low-density lipoprotein levels. It is well tolerated with minimal adverse effects and no known interactions causing rhabdomyolysis. In high doses, Omacor has pronounced cardiovascular benefits with improvement of triglycerides and various lipid parameters. Omega-3 fatty acids have also been shown to have beneficial effects on arrhythmias, inflammation, and heart failure. It may also decrease platelet aggregation and induce vasodilation. Omega-3 fatty acids also reduce atherosclerotic plaque formation and stabilize plaques preventing plaque rupture leading to acute coronary syndrome. Moreover, omega-3 fatty acids may have antioxidant properties that improve endothelial function and may contribute to its antiatherosclerotic benefits. In this review, we sought to provide the current literature on the use of omega-3 fatty acids and the potent formulation Omacor in the treatment of coronary artery disease. PMID- 21975797 TI - Clinical utility of chromosomal microarray analysis in invasive prenatal diagnosis. AB - Novel methodologies for detection of chromosomal abnormalities have been made available in the recent years but their clinical utility in prenatal settings is still unknown. We have conducted a comparative study of currently available methodologies for detection of chromosomal abnormalities after invasive prenatal sampling.A multicentric collection of a 1-year series of fetal samples with indication for prenatal invasive sampling was simultaneously evaluated using three screening methodologies: (1) karyotype and quantitative fluorescent polymerase chain reaction (QF-PCR), (2) two panels of multiplex ligation dependent probe amplification (MLPA), and (3) chromosomal microarray-based analysis (CMA) with a targeted BAC microarray. A total of 900 pregnant women provided informed consent to participate (94% acceptance rate). Technical performance was excellent for karyotype, QF-PCR, and CMA (~1% failure rate), but relatively poor for MLPA (10% failure). Mean turn-around time (TAT) was 7 days for CMA or MLPA, 25 for karyotype, and two for QF-PCR, with similar combined costs for the different approaches. A total of 57 clinically significant chromosomal aberrations were found (6.3%), with CMA yielding the highest detection rate (32% above other methods). The identification of variants of uncertain clinical significance by CMA (17, 1.9%) tripled that of karyotype and MLPA, but most alterations could be classified as likely benign after proving they all were inherited. High acceptability, significantly higher detection rate and lower TAT, could justify the higher cost of CMA and favor targeted CMA as the best method for detection of chromosomal abnormalities in at-risk pregnancies after invasive prenatal sampling. PMID- 21975799 TI - Synthesis of grandisol, the sexual attracting insect pheromone. AB - In this issue, Suh's group reported a new formal total synthesis of (+/-) grandisol featuring a palladium-catalyzed 4-exo-trig cyclization. Grandisol's interesting cyclobutane structure has been a popular test model for various cyclization methods over the years. This report summarizes Suh's formal synthesis of grandisol along with a concise review of the four-membered ring cyclization strategies employed in the synthesis of grandisol. PMID- 21975800 TI - Discovery of hepatitis C virus NS5A inhibitors as a new class of anti-HCV therapy. AB - Chronic hepatitis C virus (HCV) infection is responsible for development of liver cirrhosis and hepatocellular carcinoma. In addition to PEGylated interferon alpha, ribavirin, and HCV NS3 protease inhibitors, recently identified HCV NS5A inhibitors such as BMS-790052 showed a great promise in clinical trials as another new class of direct-acting anti-HCV therapeutics with a distinct mechanism of action. This clinical proof-of-concept study with NS5A inhibitors demonstrated that small molecules targeting a viral protein without any known enzymatic activity can also have profound antiviral effects. In conclusion, NS5A inhibitors will serve as a valuable component of future therapy for HCV patients. PMID- 21975801 TI - Myocardial postconditioning: next step to cardioprotection. AB - Myocardial ischemia is a condition in which lack of blood flow to the cardiac muscle occurs resulting in deficient oxygen and nutrient supply to the heart. The restoration of blood flow to an organ or tissue is termed reperfusion. Brief episodes of ischemia and reperfusion given after prolonged ischemia and at the onset of reperfusion denotes postconditioning. Myocardial postconditioning is a phenomenon in which myocardium from lethal ischemia-reperfusion injury is protected. However, numerous experimental studies reveal that the cardioprotective effects of postconditioning are suppressed in various pathological states. This review critically discusses the mechanisms involved in the cardioprotective effects of postconditioning and factors affecting the cardioprotective potential of myocardial postconditioning. PMID- 21975802 TI - Design and synthesis of new 1,4-dihydropyridines containing 4(5)-chloro-5(4) imidazolyl substituent as a novel calcium channel blocker. AB - New analogues of nifedipine, in which the ortho-nitro phenyl group at position 4 has been replaced by 4(5)-chloro-5(4)-imidazolyl substituent and which are able to interact with the receptor by hydrogen binding were designed, synthesized, and evaluated as calcium channel antagonists. The designed dihydropyridines were synthesized using the Hantzsch condensation and evaluated as calcium channel antagonists using the high K+ contraction of guineapig ileal longitudinal smooth muscle. A docking study was performed using the AutoDock4 program, and QSAR equations were obtained using multilinear regression. Our computational studies indicated that the oxygen of the ester (O10) and the N3' of the imidazole ring form a hydrogen bonding interaction with the NH of HIS 363 and NH of LYS354, respectively, and that the sum of the BEHp5 and RDF075p are the most significant descriptors. The results of calcium channel antagonist evaluation demonstrated that increasing the chain length in C3 and C5 ester substituents increased activity. The most potent compound was the bis-phenylpropyl ester (5l) derivative, in that it was more active than the reference drug nifedipine and that the bis-phenylethyl ester (5k) derivative had comparable activity with nifedipine. The present research revealed that the 4(5)-chloro-5(4)-imidazolyl moiety is a bioisoster of o-nitrophenyl in nifedipine and provided novel dihydropyridines with more activity as calcium channel antagonists. PMID- 21975803 TI - Antimicrobial activity of a new series of benzimidazole derivatives. AB - Due to antimicrobial importance of benzimidazoles and hydrazones, some benzimidazole-hydrazone compounds were synthesized to screen their antimicrobial activity. Structures of the synthesized compounds were elucidated by (1)H-NMR, IR and ES-MS spectral data and elemental analysis. The synthesized benzimidazole hydrazones exhibited very weak antibacterial activity. However, antifungal activity of some of the synthesized compounds was very notable against Candida species. The compounds displaying important antifungal activity were screened for their toxicity. Artemia salina 96-well assay was used to determine cytotoxicity of the compounds. Tested compounds exhibited toxicity to different extents (LD(50) = 126.33-368.72 MUg/mL). Nevertheless, determination of 3-14 folds higher LD(50) than minimum inhibitory concentration is a significant finding, which demonstrates that the compounds display antifungal activity at non-toxic concentration. PMID- 21975804 TI - A versatile synthetic approach to grandisol monoterpene pheromone. AB - A versatile and efficient synthetic procedure for the grandisol pheromone library has been established. The key feature of our synthesis involves a versatile and highly regioselective Pd(0)-catalyzed intramolecular allylic alkylation for the key cyclobutane skeleton of grandisol. In this connection, the concise synthesis of (+/-)-grandisol as well as mechanism study of Pd(0)-catalyzed regioselective cyclization as a key reaction have also been accomplished. PMID- 21975805 TI - Protective constituents against sepsis in mice from the root barks of Ulmus davidiana var. japonica. AB - In the course of isolating preventive agents against sepsis based on the in vivo assay model, eleven known compounds, (-)-catechin (1), catechin-7-O-beta apiofuranoside (2), catechin-7-O-alpha-Lrhamnopyranoside (3), catechin-3-O-alpha L-rhamnopyranoside (4), catechin-7-O-beta-D-glucopyranoside (5), butyl (+)-5' methoxyisolariciresinol-9'-O-beta-D-xylopyranoside (6), lyoniside (7), nudiposide (8), alpha-nigerose (9), butyl alpha-D-fructofuranoside (10), and procyanidin B(3) (11) were isolated from the root barks of Ulmus davidiana var. japonica. Compounds 2, 6, and 8 significantly protected against sepsis in a mouse model with survival rates of mice exposed to 10 mg/kg of LPS/D-GalN ranged from 80% 100%. Among them, 8 exhibited the most potent protective effect and decreased the plasma levels of TNF-alpha, IL-10 and ALT activity. PMID- 21975806 TI - A python-based docking program utilizing a receptor bound ligand shape: PythDock. AB - PythDock is a heuristic docking program that uses Python programming language with a simple scoring function and a population based search engine. The scoring function considers electrostatic and dispersion/repulsion terms. The search engine utilizes a particle swarm optimization algorithm. A grid potential map is generated using the shape information of a bound ligand within the active site. Therefore, the searching area is more relevant to the ligand binding. To evaluate the docking performance of PythDock, two well-known docking programs (AutoDock and DOCK) were also used with the same data. The accuracy of docked results were measured by the difference of the ligand structure between x-ray structure, and docked pose, i.e., average root mean squared deviation values of the bound ligand were compared for fourteen protein-ligand complexes. Since the number of ligands' rotational flexibility is an important factor affecting the accuracy of a docking, the data set was chosen to have various degrees of flexibility. Although PythDock has a scoring function simpler than those of other programs (AutoDock and DOCK), our results showed that PythDock predicted more accurate poses than both AutoDock4.2 and DOCK6.2. This indicates that PythDock could be a useful tool to study ligand-receptor interactions and could also be beneficial in structure based drug design. PMID- 21975807 TI - Antioxidative and anti-inflammatory effects of phenolic compounds from the roots of Ulmus macrocarpa. AB - The roots of Ulmus macrocarpa Hance (Ulmaceae) have been used as an oriental traditional medicine for the treatment of inflammation, ulcers, cancers, and parasites. Activity guided isolation from the roots of U. macrocarpa yielded three flavonoids [catechin 7-O-beta-D-apiofuranoside (1), (+)-catechin (2), taxifolin 6-C-glucopyranoside (3)], and one coumarin [fraxin (4)]. To investigate the antioxidative and anti-inflammatory effects of these compounds, DPPH radical scavenging activity and inhibitory activity against nitric oxide (NO) production in LPS-stimulated RAW 264.7 cells were examined and the expression of inducible NO synthase (iNOS) and cyclooxidase-2 (COX-2) were measured by RT-PCR and Western Blotting in HaCaT cells. Compounds 1, 2, and 3 showed moderate antioxidative activities compared with L-ascorbic acid as a positive control. NO production was reduced and the expressions of iNOS and COX-2 and their mRNA were inhibited by the addition of samples (1-4). These results suggest that the phenolic compounds from the roots of U. macrocarpa might be developed as antioxidant and anti inflammatory agents. PMID- 21975808 TI - Formulation optimization of solid dispersion of mosapride hydrochloride. AB - Mosapride citrate (MSP) is a gastroprokinetic agent that acts as a selective 5 HT(4) agonist and accelerates the gastric emptying, and is used for the treatment of acid reflux, irritable bowel syndrome, and functional dyspepsia. The purpose of this study is to investigate the solid dispersion formulations of MSP with controlled release characteristic using various polymers, elucidate the release mechanism, and characterize the interaction patterns between MSP and polymers. Solid dispersions of MSP with different drug-to-polymer ratios were prepared by a solvent evaporation method and characterized in comparison with the simple physical mixtures. Eudragit RSPO, Eudragit RLPO, hydroxypropylmethylcellulose (HPMC) or Kollidon SR was used as a controlled-release polymer along with polyvinylpyrrolidone (PVP) as a carrier. Characterization of MSP solid dispersion was performed using thermal analysis (DSC), powder X-ray diffraction (XRD), Fourier transform-infrared (FT-IR) spectroscopy, where the drug was converted from the crystalline state to amorphous state in all polymeric carriers used. In vitro dissolution studies showed that the drug release has been extended up to 24 h by using Eudragit RSPO or HPMC. Moreover, the formulations containing higher polymer content ratio showed better slow-release profile. These results indicate that the solid dispersion formulation containing PVP/Eudragit RSPO or HPMC mixture could serve as a good controlled-release system for MSP. PMID- 21975809 TI - Enhancement and mechanism of transdermal absorption of terpene-induced propranolol hydrochloride. AB - For the purpose of efficient and safe transdermal administration of propranolol hydrochloride (PHCl), effects of (+)-borneol, (+)-camphor, and alpha-bisabolol (5 w/v%) in 66.6% ethanol solution on transdermal permeation across rat skin in vitro and their enhancement mechanism was investigated with fourier transform infrared spectroscopy, differential scanning calorimetry, and PHCl-stratum corneum binding studies. Each of (+)-borneol, (+)-camphor, and alpha-bisabolol significantly increased the transdermal flux of PHCl through rat skin in comparison to the control. The enhancement mechanism of the terpenes is involved with disruption of the lipid bilayer and increase of PHCl partitioning coefficient to the stratum corneum. As for alpha-bisabolol, the protect effect of skin from dehydration and an important reason of irritation incident were observed with differential scanning calorimetry for the first time. PMID- 21975810 TI - Improved antitumor efficacy and reduced toxicity of liposomes containing bufadienolides. AB - Long-circulating liposomes are used extensively nowadays for enhancing the therapeutic effect and reducing the toxicity of anticancer drugs. In this paper, a traditional Chinese medicine, toad venom, which has long been used in the clinic for tumor therapy with unpleasant side effects, was incorporated into poloxamer modified liposomes to increase its antitumor effect and reduce its toxicity. Our preparation of bufadienolides liposomes had a particle size of around 70 nm and an entrapment efficiency of about 87.6%. Lyophilized liposomes well retained their appearance, particle size and encapsulation efficiency for 3 months. The in vitro release results verified the sustained release properties of the bufadienolides liposomes. The concentration of bufadienolides in modified liposomes that caused 50% cell killing was much lower than that of free drug for both Lovo cells and NCI-H157 cells. Compared to the bufadienolides solution and the unmodified liposomes, the bufadienolides liposomes significantly prolonged the retention time and increased the area under the curve in vivo. The antitumor efficiency of the bufadienolides liposomes against mice bearing H22 liver cancer cells and Lewis pulmonary cancer cells were 2.15 and 2.96, respectively, times that of a bufadienolides solution at the same toxicity. The safety test results demonstrated that the bufadienolides liposomes had an LD(50) that was 3.5 times the LD(50) of bufadienolides solution and caused no allergen-related or blood vessel irritation effects. All these results proved that poloxamer modified bufadienolides liposomes have improved antitumor efficacy and safety. PMID- 21975811 TI - Anti-inflammatory activity of 6-hydroxy-2,7-dimethoxy-1,4-henanthraquinone from tuberous roots of yam (Dioscorea batatas) through inhibition of prostaglandin D2 and leukotriene C4 production in mouse bone marrow-derived mast cells. AB - 6-Hydroxy-2,7-dimethoxy-1,4-phenanthraquinone (PAQ) isolated from the tuberous roots of Yam (Dioscorea batatas) inhibited cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) dependent prostaglandin D(2) (PGD(2)) generation in mouse bone marrow-derived mast cells in a concentration-dependent manner with IC(50) values of 0.08 MUM and 0.27 MUM, respectively. In the Western blotting with specific anti-COX-2 antibodies, the decrease of the quantity of PGD(2) was accompanied by a decrease in the COX-2 protein level. But PAQ did not affect COX 1 protein level. In addition, this compound inhibited 5-lipoxygenase (5-LOX) dependent production of leukotriene C(4) in a dose-dependent manner, with an IC(50) of 0.032 MUM. These results demonstrate that PAQ has a dual COX-2/5-LOX inhibitory activity. This compound also inhibited the degranulation reaction in a dose-dependent manner with an IC(50) of 2.7 MUM. Thus, these results suggest that PAQ may be useful in regulating mast cell-mediated inflammatory diseases. PMID- 21975812 TI - Simultaneous determination of eight marker compounds in the traditional herbal medicine, Sipjundaebo-tang by HPLC-DAD. AB - Sipjundaebo-tang, known as a traditional herbal medicine, has been used in the treatment of anemia, inflammation, and tumor. For simultaneous determination of eight components, namely 5-HMF, paeoniflorin, ferulic acid, cinnamaldehyde, decursinol, 6-gingerol, decursin, and glycyrrhizin in Sipjundaebo-tang, a high performance liquid chromatography-diode array detector (HPLC-DAD) method was established. In order to develop and validate this HPLC-DAD method, C(18) column (S-5 MUm, 4.6 * 250 mm) was used with gradient mobile phase at the column temperature of 35 degrees C. The mobile phase was consisted of water and methanol containing 0.1% trifluoroacetic acid. UV wavelength was set at 230, 254, 280, and 300 nm. Validation of the analytical method was evaluated by linearity, precision, and accuracy test. Calibration curve for eight marker compounds showed good linearity with R(2) > 0.9994. Limits of detection and Limits of quantification ranged from 0.01 MUg/mL to 0.13 MUg/mL and 0.03 MUg/mL to 0.41 MUg/mL, respectively. The relative standard deviations (RSDs) value of precision test, intra-day and inter-day test, was less than 1.14% and 2.54%, respectively. The results of accuracy test were varied from 98.31% to 104.88% with RSD < 2%. This developed simultaneous determination method was efficient to the quality control of Sipjundaebo-tang. PMID- 21975813 TI - The effects of cannabidiolic acid and cannabidiol on contractility of the gastrointestinal tract of Suncus murinus. AB - Cannabidiol (CBD) has been shown to inhibit gastrointestinal (GI) transit in pathophysiologic in vivo models, while having no effect in physiologic controls. The actions of the precursor of CBD, cannabidiolic acid (CBDA), have not been investigated in the GI tract. The actions of these phytocannabinoids on the contractility of the GI tract of Suncus murinus were investigated in the current study. The effects of CBDA and CBD in resting state and pre-contracted isolated intestinal segments, and on the contractile effects of carbachol and electrical field stimulation (EFS) on the intestines of S. murinus were examined. CBDA and CBD induced a reduction in resting tissue tension of isolated intestinal segments which was not blocked by the cannabinoid CB1 receptor antagonist, AM251, the CB(2) receptor antagonist AM630, or tetrodotoxin. CBDA and CBD reduced the magnitude of contractions induced by carbachol and the tension of intestinal segments that were pre-contracted with potassium chloride. In tissues stimulated by EFS, CBDA inhibited contractions induced by lower frequencies (0.1-4.0 Hz) of EFS, while CBD inhibited contractions induced by higher frequencies (4.0-20.0 Hz) of EFS. The data suggest that CBDA and CBD have inhibitory actions on the intestines of S. murinus that are not neuronallymediated or mediated via CB(1) or CB(2) receptors. PMID- 21975814 TI - Effects of epinephrine and cortisol on the analgesic activity of metyrosine in rats. AB - Some endogenous hormones (epinephrine and cortisol) can change an individual's pain threshold. Propranolol is a non-selective beta adrenergic receptor blocker which antagonises the anti-inflammatory effect of non-steroidal anti-inflammatory drugs via the beta1 and beta2 adrenergic receptors. The roles of epinephrine and cortisol were investigated in the analgesic activity of metyrosine in rats with reduced epinephrine levels induced by metyrosine. Pain threshold measurement was performed using an analgesimeter with different doses and the single or combined usage of metyrosine, prednisolone, metyrapone and propranolol in rats. Epinephrine and corticosterone levels were measured by high-performance liquid chromatography in metyrosineadministered rats. Metyrosine reduces the epinephrine levels without affecting the corticosterone levels, thereby creating an analgesic effect. It was determined that prednisolone did not have an analgesic effect in rats with normal epinephrine levels, but its analgesic activity increased with a parallel decrease in the epinephrine levels. Similarly, the combined use of prednisolone and metyrosine provided a stronger analgesic effect than that rendered by metyrosine alone. The strongest analgesic effect, however, was observed in the group of rats with the lowest epinephrine level in whom the metyrosine + prednisolone combination was administered. The findings of this study may be useful in severe pain cases in which the available analgesics are unable to relieve the individual's pain. PMID- 21975816 TI - Attenuating sevoflurane-induced cellular injury of human peripheral lymphocytes by propofol in a concentration-dependent manner. AB - Sevoflurane, one of the most commonly used inhalation anesthetics, induces apoptosis and oxidative stress in lymphocytes. Propofol, an intravenous anesthetic, exhibits antiapoptotic and antioxidative activities. Therefore, the present study aimed to investigate whether propofol attenuates sevoflurane induced cellular injury in human peripheral lymphocytes. Lymphocytes harvested from healthy volunteers were assigned to treatments with different concentrations of propofol, or 8% sevoflurane, or their combination. Propofol at concentrations of 5, 10 or 25 MUg/mL had little effect, but 50 MUg/mL propofol or 8% sevoflurane significantly reduced cell viability and mitochondrial membrane potential (DeltaPhim), and increased cell apoptosis, activation of caspase-3 and the production of intracellular reactive oxygen species, compared with untreated cells. Five and ten MUg/mL propofol attenuated the impact of sevoflurane on cell viability, apoptosis and DeltaPhim, and 5, 10 and 25 MUg/mL propofol inhibited the production of intracellular reactive oxygen species stimulated by sevoflurane. However, a combination of 50 MUg/mL propofol and 8% sevoflurane led to more severe cellular injury than sevoflurane alone. The results suggest that propofol can attenuate sevoflurane-induced cellular injury of human peripheral lymphocytes in a concentration-dependent manner, providing a rational for the clinical use of sevoflurane combined with appropriate doses of propofol. PMID- 21975815 TI - The effect of quercetin-3-O-beta-D-glucuronopyranoside on indomethacin-induced gastric damage in rats via induction of mucus secretion and down-regulation of ICAM-1 expression. AB - The mechanism of the protective effect of quercetin-3-O-beta-D glucuronopyranoside (QGC) from the leaves of Rumex aqauticus on indomethacin (IND, a representative NSAID)-induced gastric damage in rats was investigated. Pre-treatment with QGC significantly attenuated IND-induced gastric mucosal injury. An increase in myeloperoxidase (MPO) activity and expression of intercellular adhesion molecule (ICAM)-1 protein and mRNA expression of the pro inflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta, as well as a decrease in gastric mucus secretion were detected in the gastric mucosa of IND-treated rats. QGC reversed the side effect of IND on MPO activity and mucus production. Furthermore, QGC pre-treatment notably decreased ICAM-1 protein and mRNA expression of the pro-inflammatory cytokines, suggesting that QGC protection from IND-induced damage is associated with increased gastric mucus secretion, inhibition of free radical production by activated neutrophils via ICAM-1, and pro-inflammatory cytokine downregulation. PMID- 21975817 TI - Involvement of heme oxygenase-1 induction in inhibitory effect of ethyl gallate isolated from Galla Rhois on nitric oxide production in RAW 264.7 macrophages. AB - In the present study, we investigated an anti-inflammatory effect of ethyl gallate (EG) isolated from Galla Rhois as evaluated by inhibition of nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression, and a potential role of heme oxygenase-1 (HO-1) in the inhibition of NO production elicited by EG. Treatment of RAW264.7 macrophages with EG significantly inhibited the production of NO and iNOS expression stimulated by lipopolysaccharide (LPS). We also demonstrated that EG treatment increased HO-1 mRNA and protein expression, as assessed by quantitative RT-PCR and Western blot analysis. EG treatment also increased the levels of nuclear factor-erythroid 2-related factor 2, which is critical for transcriptional induction of HO-1. In addition, treatment with SnPP (tin protoporphyrin IX), a selective HO-1 inhibitor, counteracted the inhibitory effect of EG on nitrite production, suggesting that HO-1 is, at least in part, implicated in the inhibition of NO production induced by EG treatment. Taken together, these results indicate that EG isolated from Galla Rhois suppresses NO production in LPS-stimulated RAW 264.7 macrophages via HO-1 induction. PMID- 21975818 TI - Protective effect of astragaloside IV against matrix metalloproteinase-1 expression in ultraviolet-irradiated human dermal fibroblasts. AB - Ultraviolet (UV) irradiation induces skin photoaging associated with up-regulated matrix metalloproteinase (MMP) expression. Inhibition of MMP expression is suggested to alleviate photoaging induced by UV irradiation. Astragaloside IV (As IV), one of the main active ingredients of Astragalus membranaceus (Fisch) Bge, has been reported to have various biological activities. However, its anti photoaging effect has not been examined to date. In the present study, we observed the effect of As-IV on matrix metalloproteinase-1 (MMP-1) expression in UV-irradiated human dermal fibroblasts (HDFs). We found that treatment with As-IV significantly decreased UV-induced MMP-1 expression at the messenger RNA and protein levels. In addition, western blotting analysis revealed that As-IV concentration-dependently suppressed UV-induced phosphorylation of extracellular regulated protein kinase, Jun-N-terminal kinase and p38 mitogen-activated protein kinase (MAPK). Furthermore, treatment with As-IV markedly inhibited UV-induced nuclear factor kappaB (NF-kappaB) activity. These results suggest that As-IV down regulates UV-induced MMP-1 expression, perhaps through suppression of MAPK and NF kappaB activation in HDFs. As-IV is thus a potential agent for the management of skin photoaging. PMID- 21975819 TI - Inhibition of 5-lipoxygenase and skin inflammation by the aerial parts of Artemisia capillaris and its constituents. AB - The aerial parts of Artemisia capillaris Thunberg (Compositae) have been used in Chinese medicine as a liver protective agent, diuretic, and for amelioration of skin inflammatory conditions. This study was conducted to establish the scientific rationale for treating skin inflammation and to find active principles from A. capillaris. To accomplish these goals, the 70% ethanol extract of the aerial parts of A. capillaris (AR) was prepared and its 5-lipoxygenase (5-LOX) inhibitory action was studied since 5-LOX products are known to be involved in several allergic and skin inflammatory disorders. AR showed potent inhibitory activity against 5-LOX-catalyzed leukotriene production by ionophore-induced rat basophilic leukemia-1 cells, with an IC(50) of < 1.0 MUg/mL. Nine major compounds, scopoletin, scopolin, scoparone, esculetin, quercetin, capillarisin, isorhamnetin, 3-O-robinobioside, isorhamnetin 3-O-galactoside and chlorogenic acid, were isolated from A. capillaris, and their effects were examined to identify the active principle(s). Several coumarin and flavonoid derivatives were found to be 5-LOX inhibitors. In particular, esculetin and quercetin were potent inhibitors, with IC(50) values of 6.6 and 0.7 MUM, respectively. Against arachidonic acid-induced ear edema in mice, AR, and esculetin strongly inhibited edematic response. AR and esculetin also inhibited delayed-type hypersensitivity response in mice. In conclusion, AR and some of their major constituents are 5 LOX inhibitors, and these in vitro and in vivo activities may contribute to the therapeutic potential of AR in skin inflammatory disorders in traditional medicine. PMID- 21975820 TI - Inhibitory effects of sepiapterin on vascular endothelial growth factor-A-induced proliferation and adhesion in human umbilical vein endothelial cells. AB - Tetrahydrobiopterin (BH(4)) has been known to be an essential cofactor for the activities of nitric oxide (NO) synthase and aromatic amino acid hydroxylases, which are involved in physiological and pathological processes. In the present study, we report that sepiapterin, the more stable form of BH4 precursor, modulates vascular endothelial growth factor-A (VEGF-A)-induced cell proliferation and adhesion in human umbilical vein endothelial cells (HUVECs). The antiproliferative activity of sepiapterin in VEGF-A-treated HUVECs is associated with inhibition of the expression of cyclin-dependent kinases (Cdks) such as Cdk4 and Cdk2. Pretreatment with NO synthase inhibitor does not abrogate the ability of sepiapterin to inhibit VEGF-A-induced cell proliferation and adhesion, indicating that the suppressive effects of sepiapterin on VEGF-Ainduced responses are mediated by NO-independent mechanism. Finally, we show that sepiapterin modulates VEGF-A-induced cell proliferation and adhesion through down regulation of VEGF receptor-2 downstream signaling pathways. Taken together, these findings represent a novel function of sepiapterin in the regulation of angiogenesis, supporting further development and evaluation of sepiapterin as an antiangiogenic agent. PMID- 21975821 TI - Yield of practice-based depression screening in VA primary care settings. AB - BACKGROUND: Many patients who should be treated for depression are missed without effective routine screening in primary care (PC) settings. Yearly depression screening by PC staff is mandated in the VA, yet little is known about the expected yield from such screening when administered on a practice-wide basis. OBJECTIVE: We characterized the yield of practice-based screening in diverse PC settings, as well as the care needs of those assessed as having depression. DESIGN: Baseline enrollees in a group randomized trial of implementation of collaborative care for depression. PARTICIPANTS: Randomly sampled patients with a scheduled PC appointment in ten VA primary care clinics spanning five states. MEASUREMENTS: PHQ-2 screening followed by the full PHQ-9 for screen positives, with standardized sociodemographic and health status questions. RESULTS: Practice based screening of 10,929 patients yielded 20.1% positive screens, 60% of whom were assessed as having probable major depression based on the PHQ-9 (11.8% of all screens) (n = 1,313). In total, 761 patients with probable major depression completed the baseline assessment. Comorbid mental illnesses (e.g., anxiety, PTSD) were highly prevalent. Medical comorbidities were substantial, including chronic lung disease, pneumonia, diabetes, heart attack, heart failure, cancer and stroke. Nearly one-third of the depressed PC patients reported recent suicidal ideation (based on the PHQ-9). Sexual dysfunction was also common (73.3%), being both longstanding (95.1% with onset >6 months) and frequently undiscussed and untreated (46.7% discussed with any health care provider in past 6 months). CONCLUSIONS: Practice-wide survey-based depression screening yielded more than twice the positive-screen rate demonstrated through chart-based VA performance measures. The substantial level of comorbid physical and mental illness among PC patients precludes solo management by either PC or mental health (MH) specialists. PC practice- and provider-level guideline adherence is problematic without systems-level solutions supporting adequate MH assessment, PC treatment and, when needed, appropriate MH referral. PMID- 21975823 TI - Integration of intra- and extravasation in one cell-based microfluidic chip for the study of cancer metastasis. AB - Most studies of cancer metastasis focus on cancer cell invasion utilizing adhesion assays that are performed independently, and are thus limited in their ability to mimic complex cancer metastasis on a chip. Here we report the development of an integrated cell-based microfluidic chip for intra- and extravasation that combines two assays on one chip for the study of the complex cascade of cancer metastasis. This device consists of two parts; one is an intravasation chamber for the three-dimensional (3-D) culture of cancer cells using a Matrigel matrix, and the other is an extravasation chamber for the detection of metastasized cancer cells by adhesion molecules expressed by epithelial cells. In this novel system, the intravasation and extravasation processes of cancer metastasis can be studied simultaneously using four screw valves. Metastatic LOVO and non-metastatic SW480 cells were used in this study, and the invasion of LOVOs was found to be higher compared to SW480. In contrast, invasion of cells treated with metalloproteinase (MMP) inhibitors decreased within the intravasation chamber. Degraded cancer cells from the intravasation chamber were detected within the extravasation chamber under physiological conditions of shear stress, and differences in binding efficiency were also detected when CA19-9 antibody, an inhibitor of cancer cell adhesion, was used to treat degraded cancer cells. Our results support the potential usefulness of this new 3D cell-based microfluidic system as a drug screening tool to select targets for the development of new drugs and to verify their effectiveness. PMID- 21975822 TI - Inappropriate medication in a national sample of US elderly patients receiving home health care. AB - BACKGROUND: With substantial morbidity and functional impairment, older patients receiving home health care are especially susceptible to the adverse effects of unsafe or ineffective medications. Home health agencies' medication review and reconciliation services, however, provide an added mechanism of medication safety that could offset this risk. OBJECTIVE: To estimate the prevalence of potentially inappropriate medications (PIMs) among current elderly home health patients in the US. DESIGN: Cross-sectional analysis using data from the 2007 National Home and Hospice Care Survey. SUBJECTS: 3,124 home health patients 65 years of age or older on at least one medication. MAIN MEASURES: Prevalence and classification of PIM use and the association between PIM use and patient and home health agency characteristics.Key Results In 2007, 38% (95% CI: 36-41) of elderly home health patients were taking at least one PIM. Polypharmacy was associated with an increased risk of PIM use; admission to home health care from a nursing home or other sub-acute facility (compared to admission from the community) and a payment source other than Medicare or Medicaid were associated with a decreased risk of PIM use. CONCLUSIONS: The prevalence of PIM use in older home health patients is high despite potential mechanisms for improved safety. Policies to improve the review and reconciliation processes within home health agencies and to improve physician-home health clinician collaboration are likely needed to lower the prevalence of PIM use in older home health patients. PMID- 21975824 TI - UVA1 induces cyclobutane pyrimidine dimers but not 6-4 photoproducts in human skin in vivo. AB - UVB readily induces cyclobutane pyrimidine dimers, mainly thymine dimers (TTs), and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs) in DNA. These lesions result in "UVB signature mutations" found in skin cancers. We have investigated the induction of TTs and 6-4PPs in human skin in vivo by broadband UVA1, and have compared this with comparable erythemal doses of monochromatic UVB (300 nm). In vitro and ex vivo studies have shown the production of TTs, without 6-4PPs, by UVA1. We show that UVA1 induces TTs, without 6-4PPs, in the epidermis of healthy volunteers in vivo, whereas UVB induced both photoproducts. UVB induced more TTs than UVA1 for the same level of erythema. The level of UVA1-induced TTs increased with epidermal depth in contrast to a decrease that was seen with UVB. UVA1- and UVB-induced TTs were repaired in epidermal cells at a similar rate. The mechanism by which UVA1 induces TTs is unknown, but a lack of intra-individual correlation between our subjects' UVB and UVA1 minimal erythema doses implies that UVA1 and UVB erythema occur by different mechanisms. Our data suggest that UVA1 may be more carcinogenic than has previously been thought. PMID- 21975825 TI - A humanized stromal bed is required for engraftment of isolated human primary squamous cell carcinoma cells in immunocompromised mice. AB - Epithelial cancers are the most common malignancies and the greatest cause of cancer mortality worldwide. The incidence of keratinocyte-derived (non-melanoma) skin cancers is increasing rapidly. Despite access to abundant tumor tissue and ease of observation, acceptance of non-melanoma skin cancers as model carcinomas has been hindered by the lack of a reliable xenograft model. Herein we describe conditions that allow routine xeno-engraftment of primary human squamous cell carcinoma (SCCa) cells. Tumor development required creation of an appropriate stromal bed before xenografting tumor tissue onto the backs of athymic nude mice. We also demonstrate that the stromal bed must be "humanized" if primary human SCCa is to be propagated from cell suspensions. SCCa xenografts recapitulated the histological grade and phenotype of the original tumors with considerable fidelity, even after serial passage, irrespective of the histological grade of the primary human SCCa. This model, which to our knowledge is previously unreported, can be used for drug testing, as well as for studies that are relevant to the biology of primary human SCCa and other epithelial cancers. PMID- 21975826 TI - C-H activation of arenes and heteroarenes by early transition metallaborane, [(Cp*Ta)2B5H11] (Cp* = eta5-C5Me5). AB - C-H activation of arenes and heteroarenes has been achieved by a hydrogen rich tantalaborane cluster [(Cp*Ta)(2)B(5)H(11)] that leads to the formation of C-H functionalized products. Furthermore, we examined the reaction of substituted thiophene and pyrrole derivatives with tantalaborane which provided a convenient and efficient route to regio-defined C-H functionalized heteroarenes. PMID- 21975827 TI - Prevalence and associated sociodemographic factors of myopia in Korean children: the 2005 third Korea National Health and Nutrition Examination Survey (KNHANES III). AB - PURPOSE: To evaluate the sociodemographic factors of myopia and the care of myopia in Korean children. METHODS: We acquired data from 8,633 children who had completed the Health Interview Survey portion of the third Korea National Health and Nutrition Examination Survey. We assessed the prevalence of eye problems in subjects younger than 19. Sociodemographic factors that affect myopia and myopia care were identified by multivariate logistic regression analysis. RESULTS: The prevalence of child myopia in Korea was 22.6%. The results indicated a significant association between increasing age and myopia. There was a relation between the prevalence of myopia and income level. Participants living in homes owned by their parents or in urban areas as well as those with disabilities were more likely to have myopia. In terms of myopia care, age and monthly household income were significant factors. CONCLUSIONS: Public education and strategies such as a national vision screening programs are needed for appropriate vision care as children get older, and more effort needs to be made in assisting disabled persons with vision care. PMID- 21975828 TI - Relationship between macular ganglion cell complex parameters and visual field parameters after tumor resection in chiasmal compression. AB - PURPOSE: To evaluate the relationship between macular ganglion cell complex (GCC) parameters and visual field (VF) parameters in chiasmal compression and the potential for GCC parameters in order to predict the short-term postsurgical VF. METHODS: Twenty-three eyes of 12 patients with chiasmal compression and 33 control eyes were studied. All patients underwent transsphenoidal tumor resection. Before surgery a 3D scan of the macula was taken using spectral-domain optical coherence tomography. All patients underwent Humphrey 24-2 VF testing after surgery. Spearman's rank correlation coefficients were used to evaluate the relationship between the GCC parameters and VF parameters [mean deviation (MD), pattern standard deviation]. Coefficients of determination (R2) were calculated using linear regression. RESULTS: Average thickness in the patients was significantly thinner than that of controls. Average thickness, global loss volume and focal loss volume (FLV) significantly correlated with the MD. We observed the greatest R2 between FLV and MD. CONCLUSIONS: Examining the macular GCC was useful for evaluating structural damage in patients with chiasmal compression. Preoperative GCC parameters, especially FLV, may be useful in predicting visual function following surgical decompression of chiasmal compression. PMID- 21975829 TI - Intraocular pressure elevation in the early postoperative period after vitrectomy for rhegmatogenous retinal detachment. AB - PURPOSE: The purpose of this study was to determine the incidence of and risk factors for intraocular pressure (IOP) elevation within 24 h following vitrectomy for rhegmatogenous retinal detachment (RD). METHODS: We assessed 34 eyes of 34 consecutive patients with RD undergoing vitrectomy and 12 eyes of 12 patients with macular hole as controls. IOP was measured using Tonopen XL before surgery, at the end of surgery, and at 5 h and 1 day postoperatively. IOP at the end of surgery was adjusted to 15.0 +/- 2.0 mmHg. RESULTS: IOP elevation was found in five RD eyes at 5 h and in 13 1 day postoperatively. IOP in patients with RD at both 5 h and 1 day postoperatively was significantly higher than that of controls. Circumferential dimension of retinal tears and disease duration were significantly associated with IOP elevation at both 5 h and 1 day postoperatively. CONCLUSIONS: IOP elevation in the early postoperative period following vitrectomy for RD is common. The risk factors for IOP elevation include the extent of retinal tears and duration of detachment. Prophylactic treatment may be useful in eyes with higher risks of IOP elevation. PMID- 21975830 TI - A highly sensitive and selective sensing ECL platform for naringin based on beta Cyclodextrin functionalized carbon nanohorns. AB - A new electrochemiluminescent sensing platform utilizing beta-Cyclodextrin functionalized carbon nanohorns as an electrochemiluminescent amplification and sensing element was developed for sensitive detection of naringin with good specificity and excellent stability. PMID- 21975831 TI - Evoked EMG-based torque prediction under muscle fatigue in implanted neural stimulation. AB - In patients with complete spinal cord injury, fatigue occurs rapidly and there is no proprioceptive feedback regarding the current muscle condition. Therefore, it is essential to monitor the muscle state and assess the expected muscle response to improve the current FES system toward adaptive force/torque control in the presence of muscle fatigue. Our team implanted neural and epimysial electrodes in a complete paraplegic patient in 1999. We carried out a case study, in the specific case of implanted stimulation, in order to verify the corresponding torque prediction based on stimulus evoked EMG (eEMG) when muscle fatigue is occurring during electrical stimulation. Indeed, in implanted stimulation, the relationship between stimulation parameters and output torques is more stable than external stimulation in which the electrode location strongly affects the quality of the recruitment. Thus, the assumption that changes in the stimulation torque relationship would be mainly due to muscle fatigue can be made reasonably. The eEMG was proved to be correlated to the generated torque during the continuous stimulation while the frequency of eEMG also decreased during fatigue. The median frequency showed a similar variation trend to the mean absolute value of eEMG. Torque prediction during fatigue-inducing tests was performed based on eEMG in model cross-validation where the model was identified using recruitment test data. The torque prediction, apart from the potentiation period, showed acceptable tracking performances that would enable us to perform adaptive closed loop control through implanted neural stimulation in the future. PMID- 21975833 TI - [Medizinische Klinik - Intensivmedizin und Notfallmedizin]. PMID- 21975832 TI - The significance of bremsstrahlung SPECT/CT after yttrium-90 radioembolization treatment in the prediction of extrahepatic side effects. AB - Purpose Unwanted deposition of 90Y microspheres in organs other than the liver during radioembolization of liver tumours may cause severe side effects such as duodenal ulcer. The aim of this study was to evaluate the significance of posttherapy bremsstrahlung (BS) SPECT/CT images of the liver in comparison to planar and SPECT images in the prediction of radioembolization-induced extrahepatic side effects.Methods A total of 188 radioembolization procedures were performed in 123 patients (50 women, 73 men) over a 2-year period. Planar, whole-body and BS SPECT/CT imaging were performed 24 h after treatment as a part of therapy work-up.Any focally increased extrahepatic accumulation was evaluated as suspicious. Clinical follow-up and gastroduodenoscopy served as reference standards. The studies were reviewed to evaluate whether BS SPECT/CT imaging was of benefit.Results In the light of anatomic data obtained from SPECT/CT, apparent extrahepatic BS in 43% of planar and in 52% of SPECT images proved to be in the liver and hence false positive.The results of planar scintigraphy could not be analysed further since 12 images were not assessable due to high scatter artefacts. On the basis of the gastrointestinal (GI)complications and the results of gastroduodenoscopy, true positive,true-negative, false-positive and false negative results of BS SPECT and SPECT/CT imaging in the prediction of GI ulcers were determined. The sensitivity, specificity, positive and negative predictive values and the accuracy of SPECT and SPECT/CT in the prediction of GI ulcers were 13%, 88%, 8%,92% and 82%, and 87%, 100%, 100%, 99% and 99%,respectively.Conclusion Despite the low quality of BS images, BSSPECT/CT can be used as a reliable method to confirm the safe distribution of 90Y microspheres and in the prediction of GI side effects. PMID- 21975834 TI - [Acute renal failure]. PMID- 21975835 TI - [Old, older, very old : intensive care medicine facing new (old) challenges]. PMID- 21975836 TI - [Medical geriatric aspects in intensive care therapy of elderly patients]. AB - For elderly patients specific medical problems, such as the consequences of aging organs, comorbidities or geriatric syndromes must be considered in the intensive care treatment of acute diseases. Under these circumstances special instruments for geriatric assessment are particularly useful. Up to now geriatrics and intensive care medicine have made complementary contributions in the treatment of severely ill elderly patients. A closer interdisciplinary cooperation of the two disciplines could be of substantial beneficial value in the care of the sick and elderly to overcome the many open questions and pressing problems. PMID- 21975837 TI - [Drug treatment of elderly patients]. AB - Drug therapy in seniors needs to be adapted to the capacity of the aged organism. The dosages of a high number of drugs from several classes (e.g., antibiotics, low molecular weight heparins) have to be modified according to age or reduced renal function, which is a common feature in old age. Moreover, elderly patients due to their physiological alterations exhibit an increased response to drugs having an influence on renal function: diuretics, nonsteroidal anti-inflammatory drugs, inhibitors of the renin-angiotensin-aldosterone system, and contrast media. The choice of drugs should consider their age-specific tolerability, i.e., fall-risk increasing drugs and those with strong anticholinergic side effects should be avoided. Analgesics, sedatives, and narcotics have to be selected according to the age of the patient and dosages should be adapted. Multimorbidity is often treated with polypharmacy, whereby it is not unusual that this is the cause for acute hospital admission. The necessity of all drugs prescribed has to be scrutinized and the drug burden should be reduced as clinically required. PMID- 21975838 TI - [Geriatric patients in intensive care medicine. Ethical aspects]. AB - Due to demographic change and progress in medicine, the percentage of geriatric patients treated in intensive care is continuously increasing. In addition to the acute disease, many of these patients may also have chronic illnesses, multimorbidity, and cognitive limitations. In view of these conditions, it might become questionable whether intensive care treatment is medically and economically justifiable and really in the interest of the patient. From an ethical perspective, age might indeed be a factor to consider when making a decision about initiating or continuing intensive care treatment in an individual case. The denial of access to intensive care, however, cannot be justified by the advanced age of the patient alone. This would display an ethically problematic form of discrimination (ageism). PMID- 21975839 TI - [Long-term outcome of elderly patients after intensive care treatment]. AB - In general, elderly patients have poorer outcomes than younger patients after intensive care treatment. Diagnosis at admission and high age mainly influence short-term mortality within the first few months after intensive care, while comorbitities and functional status are more pivotal regarding long-term mortality. Furthermore, the main reasons for reduced physical fitness and neurocognitive consequences that often last for many months after intensive care treatment of older patients are described. Many outcome studies show that physical und mental sequelae after intensive care treatment are not only substantial but also unpredictable. Due to the constant improvement of intensive care treatment during recent decades, increasingly more patients survive their acute critical disease. Now it is time to focus on translational research to discover causal relationships between intensive care treatment and morbidity during follow-up to improve the quality of survival. PMID- 21975840 TI - [Scientific acquisition of knowledge in operative medicine. The importance of intensive care medicine]. AB - The forms of treatment in intensive care medicine and the medicinal and instrumental equipment for maintaining the circulation, pulmonary and renal functions as well as surveillance for recognition of life-threatening arrhythmias or multiorgan failure have experienced an enormous development in recent decades. Survival of traumatized or critically ill patients has been substantially improved. Due to these developments surgeons are confronted with new patterns of diseases which necessitate the development of new operative measures. This article gives a review of the most important changes in operative medicine (e.g. traumatology and vascular surgery) which can essentially be attributed to experience and success in intensive care medicine. PMID- 21975841 TI - [Mid-term outcome of cardiac surgery patients with prolonged postoperative intensive care treatment]. AB - BACKGROUND: The number of patients of advanced age and with severe comorbidities undergoing cardiac surgery is rising. Therefore, in addition to the cardiac surgery procedure itself, postoperative intensive care treatment plays an increasingly important role. The mid-term outcome of patients with postoperative long-term stays in intensive care and perioperative risk factors for an adverse outcome have not been sufficiently evaluated. MATERIAL AND METHODS: All patients who underwent cardiac surgery in our institution between 2000 and 2004 and who required intensive care treatment on our cardiac surgery intensive care unit for at least 1 week were analyzed. Patients who received heart or lung transplantation or surgery for congenital heart failure were excluded. A total of 31 perioperative variables were evaluated for 230 patients. Follow-up was performed 1 year postoperatively. RESULTS: In all, 4.3% of our patients required a prolonged stay in intensive care following cardiac surgery. Overall 1-year mortality among patients with a long-term stay in intensive care was 26.9%. The logistic regression identified postoperative renal failure requiring dialysis (OR 4.98) as the strongest predictor for mortality within the first year after surgery, followed by postoperative tracheotomy and preoperatively known atrial fibrillation. CONCLUSION: Mid-term survival among patients who underwent cardiac surgery followed by a complicated postoperative course is encouragingly high. The risk factors identified for an adverse prognosis may be helpful in improving therapy strategies and general therapy decision-making. PMID- 21975842 TI - [Diagnostic laparoscopy under dual antiplatelet therapy with clopidogrel and aspirin]. AB - Dual antiplatelet therapy using aspirin and a thienopyridine (e.g. clopidogrel) is known to be essential in patients in whom percutaneous coronary intervention with stent implantation has been performed in order to prevent stent thrombosis and its fatal consequences. On the other hand dual antiplatelet therapy increases the incidence of perioperative bleeding complications. In case of urgent or emergency surgery the risk of perioperative stent thrombosis on the one hand and the perioperative bleeding risk on the other has to be evaluated carefully in order to keep time period without sufficient platelet inhibition as short as possible. The presented case offers a strategy for managing perioperative administration of antiplatelet agents. PMID- 21975843 TI - [Volume replacement therapy options for critically ill patients]. AB - For critically ill patients with hypovolemia, volume replacement therapy is important to maintain sufficient tissue perfusion and oxygenation. Nearly all patients receive crystalloids and often additionally colloids. The advantages of the former are low costs, immediate availability, the ability to fill both the intravascular and extravascular fluid spaces and a non-allergenic potential. Administration of excessive fluid with extravasation can, however, be a problem with crystalloids and promotes the formation of tissue edema, particularly with large volumes. Colloids are more efficient volume expanders and tissue edema can be avoided. The disadvantages compared to crystalloids are the higher costs and the risk of rare but potentially severe anaphylactic reactions. Artificial colloids (hydroxyethyl starch) are cheaper than the natural colloid albumin but the safety profile is less favorable. PMID- 21975846 TI - Galanin in adrenocorticotropic hormone cells is decreased by castration. AB - Galanin (GAL) is a neuropeptide that is widely expressed in neuroendocrine tissues, including the adenohypophysis. Since GAL is expressed at higher levels in females, little attention has been paid to the regulation of GAL secretion in males. Here, we show that testosterone regulates GAL secretion in the adenohypophysis of male rats. Using double immunoelectron microscopy, we demonstrate that GAL cells possess three types of secretory granule: those with colocalization of GAL and adrenocorticotropic hormone (ACTH), those with GAL only, and those with ACTH only. The predominant granule type was that containing both GAL and ACTH, suggesting that GAL and ACTH are secreted at the same time. Indeed, adrenalectomy induced an acute decrease in the number of both GAL cells and ACTH cells. In contrast, castration resulted in a decrease in the proportion of GAL cells, while the proportion of ACTH cells remained unchanged. In addition, ACTH-strongly positive and GAL-positive cells were decreased while ACTH-weakly positive and GAL-negative cells were increased after castration. Testosterone treatment of castrated animals resulted in restoration of these levels to those of intact and sham operated animals. These results indicated that testosterone regulates GAL secretion in male animals. PMID- 21975847 TI - Distribution of immune cells and expression of interleukin receptors in ileal Peyer's patches of calves. AB - Newborn calves lack a mature immune system. The immune system develops with age, but the role of the expression of cytokine receptors in the development of immune cells of Peyer's patches (PPs) in the intestines of calves in the first 2 months has not yet been elucidated. In this study, the distribution of immune cells and the expression of interleukin (IL) receptors (R) in the ileal PPs of newborn and 2-month-old calves were investigated immunohistochemically with monoclonal antibodies against bovine CD4, CD8, IgM, gammadeltaTCR, T19, WC3, WC5, and WC6 antigens. The expression of ILRs was examined with antibodies against CD25 (IL 2Ralpha), IL-2Rgamma, IL-4R, IL-6R, IL-10R, and IL-13R antigens. CD4(+), CD8(+), gammadeltaTCR(+), T19(+), and WC6(+) cells were found to be more widely distributed in the ileal PPs of 2-month-old calves than in those of newborn calves. Moreover, the expression of CD25 (IL-2Ralpha), IL-4R, and IL-13R in the ileal PPs of 2-month-old calves was more prominent than that in newborn calves. These data suggest that the immune system of calves at 2 months of age is developed by reactions to foreign antigens and aging. PMID- 21975848 TI - Concepts of mental health: definitions and challenges. PMID- 21975850 TI - A new approach for the pistoning measurement in transtibial prosthesis. AB - BACKGROUND: Good suspension lessens the pistoning (vertical displacement) of the residual limb inside the prosthetic socket. Several methods are used for measuring the pistoning. STUDY DESIGN: Clinical trial. OBJECTIVES: To introduce and evaluate a new simple method for measuring the pistoning between the soft liner and socket in transtibial prostheses. METHODS: Five transtibial prostheses with Iceross silicone liner and shuttle lock were made for the subjects. The pistoning was measured between the liner and socket by a photographic method in single limb support on the prosthetic limb (full weight bearing), non-weight bearing and under three static axial loading conditions (30, 60 and 90 N). RESULTS: This new method enabled us to measure the pistoning between the liner and prosthetic socket. The reproducibility of measurements in different trials of one session and between two sessions by two observers was shown to be high. The average of displacement between the liner and socket was about 9 mm in non-weight bearing compared with full weight bearing. Furthermore, as we expected, the average of pistoning increased consistently by adding the loads. CONCLUSIONS: This new method provides for easy and inexpensive determination of pistoning between the liner and socket by every prosthetist in clinical settings. PMID- 21975851 TI - Sagittal plane kinematics of the foot during passive ankle dorsiflexion. AB - BACKGROUND: Measurement of ankle joint dorsiflexion is an essential examination technique that needs to be performed prior to prescription of foot orthoses since the presence or absence of ankle equinus will affect the design of such devices. The purpose of this study was to investigate the effect of foot posture on sagittal plane kinematics of various foot segments during passive dorsiflexion. STUDY DESIGN: Comparative repeated measures design. OBJECTIVES: To determine the effect of foot posture on inter segmental kinematics during passive dorsiflexion. METHODS: An optoelectronic movement analysis system was employed to collect kinematic data. A validated marker set (Oxford Foot Model) was applied to 16 subjects (12 males, 4 females) with a mean age of 35.5 years (range 20-56 years), who provided informed consent. An upward force was applied to the forefoot until maximum resistance. Sagittal movement of the hindfoot and forefoot segments along with the whole foot movement were analyzed in the pronated, neutral and supinated foot postures. RESULTS: While maximum foot dorsiflexion angle showed a significant difference between the three postures (p = 0.000) the actual recorded difference between the neutral and supinated postures was only 2.49 degrees . For the hindfoot and forefoot segments, mean angle range of movement for the pronated foot posture was significantly higher than the other foot postures. The forefoot to hindfoot angle demonstrated a significant (p = 0.005) increase during dorsiflexion between the pronated and supinated postures. These results indicate that during passive dorsiflexion, the forefoot travels through a greater degree of movement than the hindfoot. CONCLUSIONS: While the maximum foot dorsiflexion angle differs significantly between the pronated and supinated foot postures, hindfoot movement also varies significantly between foot postures. Furthermore, the forefoot to tibia angle travels through a greater range than the hindfoot to tibia angle, in all three foot postures. The hindfoot to forefoot angle does not remain constant during passive dorsiflexion, but increases upon application of a dorsiflexing force, indicating that the forefoot movement cannot be eliminated completely by placing the foot in any particular posture. PMID- 21975852 TI - Characterization of the self-association of human interferon-alpha2b, albinterferon-alpha2b, and pegasys. AB - The self-association of human interferon-alpha2b (hIFN-alpha2b), albinterferon alpha2b (a recombinant protein with human serum albumin and hIFN-alpha2b peptides fused together in a single polypeptide chain), and Pegasys (PEGylated hIFN alpha2a) was characterized by analytical ultracentrifugation analyses. By examining the apparent sedimentation coefficient distribution profiles of each protein at different concentrations, it was concluded that the above three proteins are self-associating in albinterferon-alpha2b formulation buffer. By model fitting of sedimentation data using SEDANAL software, the stoichiometry and equilibrium constants of the self-association of these proteins were characterized. The self-association of hIFN-alpha2b results in the formation of stable dimers, fast-reversible tetramers, octamers, and hexadecamers. In contrast, although both albinterferon-alpha2b and Pegasys are self-associated, their self-association stoichiometries are significantly different from that of hIFN-alpha2b. The self-association of albinterferon-alpha2b results in the formation of reversible dimers and trimers, whereas the self-association of Pegasys gives only reversible dimers. The self-association behaviors of hIFN alpha2b and albinterferon-alpha2b involves attractive electrostatic forces, which can be suppressed to a negligible level in low pH (pH 4.0-4.5) and high salt concentration (400 mM NaCl) buffer, allowing quantification of their size variant contents by sedimentation velocity analysis. PMID- 21975853 TI - Hepatoprotective activity of Tribulus terrestris extract against acetaminophen induced toxicity in a freshwater fish (Oreochromis mossambicus). AB - The potential protective role of Tribulus terrestris in acetaminophen-induced hepatotoxicity in Oreochromis mossambicus was investigated. The effect of oral exposure of acetaminophen (500 mg/kg) in O. mossambicus at 24-h duration was evaluated. The plant extract (250 mg/kg) showed a remarkable hepatoprotective activity against acetaminophen-induced hepatotoxicity. It was judged from the tissue-damaging level and antioxidant levels in liver, gill, muscle and kidney tissues. Further acetaminophen impact induced a significant rise in the tissue damaging level, and the antioxidant level was discernible from the enzyme activity modulations such as glutamate oxaloacetic transaminase, glutamate pyruvic transaminase, alkaline phosphatase, acid phosphatase, glucose-6-phosphate dehydrogenase, lactate dehydrogenase, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase, lipid peroxidase and reduced glutathione. The levels of all these enzymes have significantly (p < 0.05) increased in acetaminophen-treated fish tissues. The elevated levels of these enzymes were significantly controlled by the treatment of T. terrestris extract (250 kg/mg). Histopathological changes of liver, gill and muscle samples were compared with respective controls. The results of the present study specify the hepatoprotective and antioxidant properties of T. terrestris against acetaminophen-induced toxicity in freshwater fish, O. mossambicus. PMID- 21975854 TI - Endocrine differentiation of rat enterocytes in long-term three-dimensional co culture with intestinal myofibroblasts. AB - The proliferation and differentiation of the small intestinal epithelium depends on the microenvironment surrounding the stem cells, such as intestinal subepithelial myofibroblasts. Although there have been many culture studies of intestinal epithelial-mesenchymal interaction, a culture which allows long-term observations has been difficult. This study investigated the influence of intestinal subepithelial myofibroblasts on the proliferation and differentiation of intestinal epithelial cells with a relatively long-term observation of 3 wk using a 3D co-culture system. Cultured rat intestinal subepithelial myofibroblasts, obtained from the duodenum, were embedded in collagen gel and cells from the rat intestinal epithelial cell line IEC-6 seeded onto it. Histologic sections of the cell-embedded gels were made and histochemical and immunohistochemical examinations were carried out in conjunction with expression analysis of the pancreatic duodenal homeobox 1 (pdx-1) transcription factor in IEC-6 cells. The IEC-6 cells showed increased proliferation and displayed characteristic endocrine features when co-cultured with rat intestinal subepithelial myofibroblasts, arranging themselves into multilayer structures and becoming cuboidal, with abundant cytoplasm and oval nuclei. Some IEC-6 cells were immunohistochemically positive for chromogranin A and glicentin. They also expressed the pdx-1 transcription factor at both the mRNA and protein levels. The number and percentage of chromogranin A-positive cells increased with culture time, whereas no increase was observed in cells cultured without rat intestinal subepithelial myofibroblasts. The present study using a long-term 3D co-culture model has obtained evidence of the participation of intestinal subepithelial myofibroblasts in enteroendocrine differentiation, supported by the expression of pdx-1 and glicentin production. PMID- 21975856 TI - Infantile childhood onset of spinocerebellar ataxia type 2. AB - Spinocerebellar ataxia type 2 (SCA2) is a late-onset autosomal dominant cerebellar ataxia caused by triplet CAG/CTG expansion in the ATX2 gene. The initial symptoms usually appear when subjects are in their 30s.Pediatric onset is less common and usually associated with larger triplet expansions. We here report the case of a 1-year-old girl who presented with facial dysmorphism,dystonic features, developmental delay, and retinitis pigmentosa.She was diagnosed as carrying an expanded CAG/CTG tract (92 repeats) before a molecular diagnosis of SCA2 was made in her father. Facial dysmorphism associated with developmental delay and retinitis pigmentosa in early childhood should prompt a careful family investigation for ataxia and study of ATX2. PMID- 21975855 TI - Calcium as a trigger for cerebellar long-term synaptic depression. AB - Cerebellar long-term depression (LTD) is a form of long-term synaptic plasticity that is triggered by calcium(Ca2+) signals in the postsynaptic Purkinje cell. This Ca2+comes both from IP3-mediated release from intracellular Ca2+ stores, as well as from Ca2+ influx through voltage-gated Ca2+ channels. The Ca2+ signal that triggers LTD occurs locally within dendritic spines and is due to supralinear summation of signals coming from these two Ca2+ sources. The properties of this postsynaptic Ca2+signal can explain several features of LTD, such as its associativity, synapse specificity, and dependence on thetiming of synaptic activity, and can account for the slow kinetics of LTD expression. Thus, from a Ca2+ signaling perspective, LTD is one of the best understood forms of synaptic plasticity. PMID- 21975857 TI - Hyperglycemia as a predictor of poor outcome at discharge in patients with acute spontaneous cerebellar hemorrhage. AB - Acute stroke patients commonly suffer from hyperglycemia. However, the relationship between hyperglycemia and poor outcome after discharge of patients with acute cerebellar hemorrhage (CH) had not been hitherto investigated.Sixty two patients with acute spontaneous CH were retrospectively analyzed. The consciousness level, blood glucose/sugar (BS) on arrival and maximum diameter of hematoma, etc., were obtained. Patient prognosis was scored by the Glasgow Outcome Scale (GOS) at discharge and we divided them into good outcome (GOS score of 4 or 5) and poor outcome (GOS score of 1 or 2 or 3) groups. The association between early outcome and clinical characteristics were investigated by multivariate logistic regression. There were 33 (53.4%) patients in the poor outcome group and 29(46.6%) in the good outcome group. The initial BS was significantly higher in the poor outcome group (186.4+/-57 mg/dl) compared with good outcome group (136.6+/-31.1 mg/dl)(p<0.001). BS>=140 mg/dl (OR=25.217, p=0.008) and maximum diameter of hematoma >=3 cm (OR=216.422, p<0.001) were independently correlated with poor outcome. We report the first study that hyperglycemia (BS>=140 mg/dl) on arrival and maximum diameter of hematoma >=3 cm were found to be strong predictive factors of poor outcome at discharge in patients with acute spontaneous CH. PMID- 21975858 TI - Cerebellar cognitive affective syndrome in Machado Joseph disease: core clinical features. AB - The cerebellum is no longer considered a purely motor control device, and convincing evidence has demonstrated its relationship to cognitive and emotional neural circuits. The aims of the present study were to establish the core cognitive features in our patient population and to determine the presence of Cerebellar Cognitive Affective Syndrome (CCAS) in this group. We recruited 38 patients with spinocerebellar ataxia type 3 (SCA3) or Machado-Joseph disease (MJD)-SCA3/MJD and 31 controls. Data on disease status were recorded (disease duration, age, age at onset, ataxia severity, and CAG repeat length). The severity of cerebellar symptoms was measured using the International Cooperative Ataxia Rating Scale and the Scale for the Assessment and Rating of Ataxia. The neuropsychological assessment consisted of the Mini-Mental State Examination, Clock Drawing Test, Wechsler Adult Intelligence Scale, Rey-Osterrieth Complex Figure, Wisconsin Card Sorting Test, Stroop Color-Word Test, Trail-Making Test, Verbal Paired Associates, and verbal fluency tests. All subjects were also submitted to the Hamilton Anxiety Scale and Beck Depression Inventory. After controlling for multiple comparisons, spatial span, picture completion, symbol search, Stroop Color-Word Test, phonemic verbal fluency, and Trail-Making Tests A and B were significantly more impaired in patients with SCA3/MJD than in controls. Executive and visuospatial functions are impaired in patients with SCA3/MJD, consistent with the symptoms reported in the CCAS. We speculate on a possible role in visual cortical processing degeneration and executive dysfunction in our patients as a model to explain their main cognitive deficit. PMID- 21975859 TI - Which eligible breast conservation patients choose mastectomy in the setting of newly diagnosed breast cancer? AB - PURPOSE: Breast conserving therapy (BCT) and mastectomy offer equivalent survival for women with newly diagnosed breast cancer (BrCa). Despite this, many women eligible for BCT elect mastectomy. Herein, we identify factors associated with choosing ipsilateral mastectomy instead of BCT when mastectomy is not required. METHODS: Between July 2007 and June 2010, 520 women with BrCa were treated by a single surgeon who prospectively documented patient eligibility for BCT. For patients who did not require mastectomy (n=392), we evaluated associations between treatment choice and potential predictors using odds ratios (ORs) obtained from multivariable logistic regression models. P values<=0.0029 were significant after correction for multiple testing. RESULTS: Of 392 women eligible for BCT, 106 (27%) chose mastectomy and 286 (73%) chose BCT. Multivariate analysis found an increased likelihood of electing mastectomy over BCT for patients with no comorbidities (OR 5.4; P<0.001) and those with previous mastectomy (OR 23.2; P<0.001). MRI and biopsy findings were associated with treatment choice because patients who had a second-site biopsy positive for cancer in the same quadrant as the index tumor were more likely to elect mastectomy compared with patients with no additional MRI abnormalities (OR 4.3; P=0.0027). No association existed on multivariate analysis between choice of mastectomy and patient age, family history, or tumor stage. CONCLUSIONS: One in four eligible BCT patients chooses mastectomy. Factors independently associated with choosing mastectomy over BCT include findings of second-site biopsy, previous mastectomy, and absence of comorbidities but not primary tumor characteristics. Further study into a patient's choice for mastectomy is warranted. PMID- 21975860 TI - Antioxidant therapy in hemodialysis patients: a systematic review. AB - Antioxidants have been used as therapies to decrease oxidative stress and improve CVD risk in hemodialysis (HD) patients. A systematic search of the Medline database (search date 30 April 2011) found 56 studies investigating the effects of antioxidant therapies on biomarkers of oxidative stress (53 studies) or clinical outcomes (3 studies). The majority were small trials using a nonrandomized open-label design with a single HD group (no HD controls). Alpha tocopherol was the most investigated antioxidant, with 20/25 studies reporting that this vitamin decreased oxidative stress, and one clinical outcome trial in 196 patients finding that it protected against secondary CVD. Studies using vitamin C were more equivocal, with 4/11 showing decreased oxidative stress and one clinical outcome trial showing no effect on morbidity or mortality. N acetylcysteine was the most efficacious agent, with 4/4 studies indicating a decrease in oxidative stress and one trial (n=134) showing reduced CVD events. Seven studies have used therapy containing a combination of antioxidants, with five of these reporting decreased oxidative stress. Most intervention studies in HD patients, such as statin therapy and increased dialysis dose, have failed to show improvement in CVD outcomes. Two intervention trials using different antioxidants have found CVD benefits, suggesting that this line of therapy is effective in this resistant population. These studies require validation in larger, adequately powered trials. PMID- 21975861 TI - Altered expression of microRNA miR-146a correlates with the development of chronic renal inflammation. AB - MicroRNAs (miRNAs) are highly conserved small non-coding RNAs that act as post transcriptional regulators of target mRNA. In this study, we sought to identify the microRNA underlying local inflammation in a murine model of chronic kidney disease (CKD). In microarray analysis of kidneys, the expression of miR-146a/b was elevated in B6.MRLc1 CKD mice that spontaneously develop renal inflammation with age. Primary-microRNA analysis found that elevated miR-146a/b expression in the kidneys of B6.MRLc1 mice was mainly derived from miR-146a rather than miR 146b, and this expression increased with the development of CKD. Histopathological scores for glomerular and interstitial lesions, mRNA expression of inflammatory mediators, and macrophage infiltration were significantly higher in B6.MRLc1 than C57BL/6 mice and were positively correlated with miR-146a expression. In situ hybridization and laser microdissection-RT-PCR showed that miR-146a expression in interstitial lesions containing inflammatory cells was higher than in the glomerulus. The increased expression of the inflammatory associated genes RELA, IRAK1, IL1B, IL10, and CXCLs was noted in miR-146a/b silenced human monocytes. The amount of miR-146a was higher in urine sediments of B6.MRLc1 than of C57BL/6 mice. Thus, miR-146a expression in the kidneys and its urinary excretion was specifically associated with the development of interstitial lesions and correlated with inflammatory cell infiltration. PMID- 21975862 TI - Interleukin-1 accounts for intrarenal Th17 cell activation during ureteral obstruction. AB - Interleukin 17A-secreting T-helper 17 (Th17) cells are pathogenic in inflammatory kidney diseases, but their intrarenal regulation is poorly understood. In order to better define Th17 cell dynamics during interstitial inflammation, we utilized the mouse unilateral ureteral obstruction model to analyze inflammatory cell subtypes by multicolor flow cytometry and cell sorting and by effects on in vitro generated Th17 cells. Interleukin 17A expression localized to CCR6(+)CCR4(+/ )CD4(+) T-cells and progressively increased in obstructed kidneys. The number of CCR6(+)CD4(+) T-cells increased over 10-fold by 72 h, were enriched for interleukin 17A production, and were highly proliferative based on in vivo bromodeoxyuridine incorporation. Secreted products of leukocytes isolated from obstructed kidneys enhanced the interleukin 17A production of in vitro-generated Th17 cells. This Th17-enhancing activity was identified as interleukin-1 produced by renal dendritic cells and monocytes. The in vivo validity of these findings was confirmed in mice lacking the interleulin-1 receptor and in mice treated with a recombinant interleukin-1 receptor antagonist, each of which exhibited reduced intrarenal Th17 activity compared with control mice. Thus, the inflamed kidney accumulates CCR6(+) Th17 cells that undergo activation and proliferation. Production of interleukin 1 family cytokines by resident dendritic cells and infiltrating monocytes enhances intrarenal Th17 activation in acute kidney injury. PMID- 21975864 TI - Vascular access surveillance: an ongoing controversy. AB - Hemodialysis vascular access surveillance continues to be widely recommended despite ongoing controversy as to its benefit in prolonging access patency compared with clinical monitoring alone. The most common screening tests are access blood flow and dialysis venous pressure measurements. When surveillance test results cross a predetermined threshold, accesses are referred for intervention with correction of stenosis to reduce future thrombosis and prolong access survival. Current surveillance strategies have four components: (1) underlying condition; (2) screening test; (3) intervention; and (4) outcomes. However, limitations exist within each component that may prevent achieving the desired outcomes. This review discusses these limitations and their consequences. To date, randomized controlled trials have not consistently shown that surveillance improves outcomes in grafts, and there is limited evidence that surveillance reduces thrombosis without prolonging the life of native fistulae. In conclusion, current evidence does not support the concept that all accesses should undergo routine surveillance with intervention. PMID- 21975865 TI - AKI in the ICU: definition, epidemiology, risk stratification, and outcomes. AB - Acute kidney injury (AKI) has emerged as a major public health problem that affects millions of patients worldwide and leads to decreased survival and increased progression of underlying chronic kidney disease (CKD). Recent consensus criteria for definition and classification of AKI have provided more consistent estimates of AKI epidemiology. Patients, in particular those in the ICU, are dying of AKI and not just simply with AKI. Even small changes in serum creatinine concentrations are associated with a substantial increase in the risk of death. AKI is not a single disease but rather a syndrome comprising multiple clinical conditions. Outcomes from AKI depend on the underlying disease, the severity and duration of renal impairment, and the patient's renal baseline condition. The development of AKI is the consequence of complex interactions between the actual insult and subsequent activation of inflammation and coagulation. Contrary to the conventional view, recent experimental and clinical data argue against renal ischemia-reperfusion as a sine qua non condition for the development of AKI. Loss of renal function can occur without histological signs of tubular damage or even necrosis. The detrimental effects of AKI are not limited to classical well-known symptoms such as fluid overload and electrolyte abnormalities. AKI can also lead to problems that are not readily appreciated at the bedside and can extend well beyond the ICU stay, including progression of CKD and impaired innate immunity. Experimental and small observational studies provide evidence that AKI impairs (innate) immunity and is associated with higher infection rates. PMID- 21975863 TI - Resveratrol improves renal microcirculation, protects the tubular epithelium, and prolongs survival in a mouse model of sepsis-induced acute kidney injury. AB - The mortality rate of patients who develop acute kidney injury during sepsis nearly doubles. The effectiveness of therapy is hampered because it is usually initiated only after the onset of symptoms. As renal microvascular failure during sepsis is correlated with the generation of reactive nitrogen species, the therapeutic potential of resveratrol, a polyphenol vasodilator that is also capable of scavenging reactive nitrogen species, was investigated using the cecal ligation and puncture (CLP) murine model of sepsis-induced acute kidney injury. Resveratrol when given at 5.5 h following CLP reversed the decline in cortical capillary perfusion, assessed by intravital microscopy, at 6 h in a dose dependent manner. Resveratrol produced the greatest improvement in capillary perfusion and increased renal blood flow and the glomerular filtration rate without raising systemic pressure. A single dose at 6 h after CLP was unable to improve renal microcirculation assessed at 18 h; however, a second dose at 12 h significantly improved microcirculation and decreased the levels of reactive nitrogen species in tubules, while improving renal function. Moreover, resveratrol given at 6, 12, and 18 h significantly improved survival. Hence, resveratrol may have a dual mechanism of action to restore the renal microcirculation and scavenge reactive nitrogen species, thus protecting the tubular epithelium even when administered after the onset of sepsis. PMID- 21975866 TI - Synthesis of silane surface modified ZnO quantum dots with ultrastable, strong and tunable luminescence. AB - Surface modified ZnO quantum dots (QDs) with ultrastable, strong and tunable luminescence have been successfully prepared via silanization during the growth process by (3-(2,3-epoxypropoxy)propyl)trimethoxysilane. The as-prepared ZnO QDs are demonstrated to be promising for anti-counterfeit applications in expensive high-end liquors, etc. PMID- 21975867 TI - Guiding, distribution, and storage of trains of shape-dependent droplets. AB - We present a simple method of guiding, distributing, and storing of a train of shape-dependent droplets by using side flows, cavity guiding tracks, and storage chambers. The squeezing flow makes a train of flattened droplets to align to one side of the wall and the pushing flow guides it to one of the designated guiding tracks. Then the guided droplets move along the guiding track due to the lowered surface energy when they flow along the track. In addition, simultaneous droplet guiding and storing process has been demonstrated. An array of storage chambers placed in each track could store each train containing differently concentrated droplets. The proposed method will be useful for distribution of droplets for further processes or storing for multiplex, large-scale, dynamic assays over time. PMID- 21975868 TI - A-kinase anchoring proteins: temporal and spatial regulation of intracellular signal transduction in the cardiovascular system. PMID- 21975869 TI - Norepinephrine uptake mechanisms in cardiovascular disease deserve our attention. PMID- 21975870 TI - Increases in blood pressure and heart rate induced by caffeine are inhibited by ( )-epigallocatechin-3-O-gallate: involvement of catecholamines. AB - In a previous experiment, (-)-epigallocatechin-3-O-gallate (EGCG) reduced caffeine-induced locomotor activity and stereotyped behaviors and inhibited caffeine-induced neuronal stimulant activity. This research was performed to give additional evidence that EGCG counteracts caffeine-induced stimulant effects in animals. EGCG inhibited caffeine-induced cardiovascular activation measures, such as arterial pressure and heart rate. In addition, the increases in the levels of adrenaline and noradrenaline in the blood induced by caffeine was reduced by EGCG. We suggest that EGCG may reduce caffeine-induced increases in blood pressure and heart rate and may decrease the levels of catecholamines in the blood. Therefore, EGCG counteracts caffeine-induced cardiovascular activity. The stimulant effects of caffeine should be reduced by the amount of EGCG in green tea. PMID- 21975871 TI - Ion transporting proteins of human bronchial epithelium. AB - The electrolyte transport system across human airway epithelium followed by water movement is essential for the normal mucociliary clearance that allows the maintenance of the aseptic condition of the respiratory tract. The function of epithelial cells is to control and regulate ionic composition and volume of fluids in the airways. Various types of proteins taking part in assuring effective ions and water transport in apical and basolateral membranes of the airway epithelium have been found (e.g., CFTR, ENaC, CaCC, ORCC, potassium channels, NaKATPase, aquaporins). The paper reviews the current state of the art in the field of ion channels, transporters, and other signaling proteins identified in the human bronchial epithelium. PMID- 21975874 TI - Genetic deletion of the P2Y2 receptor offers significant resistance to development of lithium-induced polyuria accompanied by alterations in PGE2 signaling. AB - Lithium (Li)-induced polyuria is due to resistance of the medullary collecting duct (mCD) to the action of arginine vasopressin (AVP), apparently mediated by increased production of PGE(2). We previously reported that the P2Y(2) receptor (P2Y(2)-R) antagonizes the action of AVP on the mCD and may play a role in Li induced polyuria by enhancing the production of PGE(2) in mCD. Hence, we hypothesized that genetic deletion of P2Y(2)-R should ameliorate Li-induced polyuria. Wild-type (WT) or P2Y(2)-R knockout (KO) mice were fed normal or Li added diets for 14 days and euthanized. Li-induced polyuria, and decreases in urine osmolality and AQP2 protein abundance in the renal medulla, were significantly less compared with WT mice despite the lack of differences in Li intake or terminal serum or inner medullary tissue Li levels. Li-induced increased urinary excretion of PGE(2) was not affected in KO mice. However, prostanoid EP(3) receptor (EP3-R) protein abundance in the renal medulla of KO mice was markedly lower vs. WT mice, irrespective of the dietary regimen. The protein abundances of other EP-Rs were not altered across the groups irrespective of the dietary regimen. Ex vivo stimulation of mCD with PGE(2) generated significantly more cAMP in Li-fed KO mice (130%) vs. Li-fed WT mice (100%). Taken together, these data suggest 1) genetic deletion of P2Y(2)-R offers significant resistance to the development of Li-induced polyuria; and 2) this resistance is apparently due to altered PGE(2) signaling mediated by a marked decrease in EP3-R protein abundance in the medulla, thus attenuating the EP3-mediated decrease in cAMP levels in mCD. PMID- 21975872 TI - Imatinib ameliorates renal morphological changes in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent malignant hypertension. AB - The present study was performed to assess the effects of the platelet-derived growth factor (PDGF) receptor kinase inhibitor imatinib mesylate on the renal morphological changes occurring during the development of malignant hypertension in transgenic rats with inducible expression of the Ren2 gene [TGR(Cyp1a1Ren2)]. Arterial blood pressure was measured by radiotelemetry in male Cyp1a1-Ren2 rats during control conditions and during dietary administration of indole-3-carbinol (I3C; 0.3%) for 14 days to induce malignant hypertension. Rats induced with I3C (n = 5) had higher mean arterial pressures (178 +/- 4 vs. 109 +/- 2 mmHg, P < 0.001) and increased urinary albumin excretion (Ualb; 13 +/- 5 vs. 0.6 +/- 0.2 mg/day) compared with noninduced rats (n = 5). Chronic administration of imatinib (60 mg.kg(-1).day(-1) in drinking water, n = 5) did not alter the magnitude of the hypertension (176 +/- 8 mmHg) but prevented the increase in Ualb (1.6 +/- 0.3 mg/day). Quantitative analysis of proliferating cell nuclear antigen using immunohistochemistry demonstrated increased proliferating cell number in cortical tubules (38 +/- 5 vs. 18 +/- 1 cells/mm(2)) and cortical interstitium (40 +/- 7 vs. 13 +/- 6 cells/mm(2)) of hypertensive rat kidneys. Renal cortical fibrosis evaluated by picrosirius red staining showed increased collagen deposition in kidneys of the hypertensive rats (1.6 +/- 0.1 vs. 0.4 +/- 0.1% of cortical area). Imatinib attenuated the increase in proliferating cell number in cortical tubules and interstitium (22 +/- 5 vs. 38 +/- 5 and 22 +/- 6 vs. 40 +/- 7 cells/mm(2), respectively) and reduced the degree of collagen deposition (0.8 +/- 0.2 vs. 1.6 +/- 0.1%) in the kidneys of hypertensive rats. These findings demonstrate that the renal pathological changes that occur during the development of malignant hypertension in Cyp1a1-Ren2 rats involve activation of PDGF receptor kinase. PMID- 21975873 TI - Increase of sodium delivery stimulates the mitochondrial respiratory chain H2O2 production in rat renal medullary thick ascending limb. AB - The mitochondria-rich epithelial cells of the renal medullary thick ascending limb (mTAL) reabsorb nearly 25% of filtered sodium (Na(+)) and are a major source of cellular reactive oxygen species. Although we have shown that delivery of Na(+) to the mTAL of rats increases superoxide (O(2)(.-)) production in mTAL, little is known about H(2)O(2) production, given the lack of robust and selective fluorescent indicators for determining changes within the whole cell, specifically in the mitochondria. The present study determined the effect of increased tubular flow and Na(+) delivery to mTAL on the production of mitochondrial H(2)O(2) in mTAL. H(2)O(2) responses were determined in isolated, perfused mTAL of Sprague-Dawley rats using a novel mitochondrial selective fluorescent H(2)O(2) indicator, mitochondria peroxy yellow 1, and a novel, highly sensitive and stable cytosolic-localized H(2)O(2) indicator, peroxyfluor-6 acetoxymethyl ester. The results showed that mitochondrial H(2)O(2) and cellular fluorescent signals increased progressively over a period of 30 min following increased tubular perfusion (5-20 nl/min), reaching levels of statistical significance at ~10-12 min. Responses were inhibited with rotenone or antimycin A (inhibitors of the electron-transport chain), polyethylene glycol-catalase and by reducing Na(+) transport with furosemide or ouabain. Inhibition of membrane NADPH oxidase with apocynin had no effect on mitochondrial H(2)O(2) production. Cytoplasmic H(2)O(2) (peroxyfluor-6 acetoxymethyl ester) increased in parallel with mitochondrial H(2)O(2) (mitochondria peroxy yellow 1) and was partially attenuated (~65%) by rotenone and completely inhibited by apocynin. The present data provide clear evidence that H(2)O(2) is produced in the mitochondria in response to increased flow and delivery of Na(+) to the mTAL, and that whole cell H(2)O(2) levels are triggered by the mitochondrial reactive oxygen species production. The mitochondrial production of H(2)O(2) may represent an important target for development of more effective antioxidant therapies. PMID- 21975876 TI - Beyond measure: teaching clinical skills. PMID- 21975875 TI - High glucose-induced RhoA activation requires caveolae and PKCbeta1-mediated ROS generation. AB - Glomerular matrix accumulation is a hallmark of diabetic nephropathy. We previously showed that RhoA activation by high glucose in mesangial cells (MC) leads to matrix upregulation (Peng F, Wu D, Gao B, Ingram AJ, Zhang B, Chorneyko K, McKenzie R, Krepinsky JC. Diabetes 57: 1683-1692, 2008). Here, we study the mechanism whereby RhoA is activated. In primary rat MC, RhoA activation required glucose entry and metabolism. Broad PKC inhibitors (PMA, bisindolylmaleimide, Go6976), as well as specific PKCbeta blockade with an inhibitor and small interfering RNA (siRNA), prevented RhoA activation by glucose. PKCbeta inhibition also abrogated reactive oxygen species (ROS) generation by glucose. The ROS scavenger N-acetylcysteine (NAC) or NADPH oxidase inhibitors apocynin and DPI prevented glucose-induced RhoA activation. RhoA and some PKC isoforms localize to caveolae. Chemical disruption of these microdomains prevented RhoA and PKCbeta1 activation by glucose. In caveolin-1 knockout cells, glucose did not induce RhoA and PKCbeta1 activation; these responses were rescued by caveolin-1 reexpression. Furthermore, glucose-induced ROS generation was significantly attenuated by chemical disruption of caveolae and in knockout cells. Downstream of RhoA signaling, activator protein-1 (AP-1) activation was also inhibited by disrupting caveolae, was absent in caveolin-1 knockout MC and rescued by caveolin-1 reexpression. Finally, transforming growth factor (TGF)-beta1 upregulation, mediated by AP-1, was prevented by RhoA signaling inhibition and by disruption or absence of caveolae. In conclusion, RhoA activation by glucose is dependent on PKCbeta1-induced ROS generation, most likely through NADPH oxidase. The activation of PKCbeta1 and its downstream effects, including upregulation of TGF beta1, requires caveolae. These microdomains are thus important mediators of the profibrogenic process associated with diabetic nephropathy. PMID- 21975877 TI - An Intergenerational Reflection on the First Night on Call-plus ca change, plus c'est la meme chose? (The More Things Change, the More They Stay the Same?). PMID- 21975879 TI - Measuring progressive independence with the resident supervision index: theoretical approach. AB - BACKGROUND: Graduate medical education is based on an on-the-job training model in which residents provide clinical care under supervision. The traditional method is to offer residents graduated levels of responsibility that will prepare them for independent practice. However, if progressive independence from supervision exceeds residents' progressive professional development, patient outcomes may be at risk. Leaders in graduate medical education have called for "optimal" supervision, yet few studies have conceptually defined what optimal supervision means and whether optimal care is theoretically compatible with progressive independence, nor have they developed a test for progressive independence. OBJECTIVE: This research develops theory and analytic models as part of the Resident Supervision Index to quantify the intensity of supervision. METHODS: We introduce an explicit set of assumptions for an ideal patient centered theory of optimal supervision of resident-provided care. A critical assumption is that informed attending staff will use available resources to optimize patient outcomes first and foremost, with residents gaining clinical competencies by contributing to optimal care. Next, we derive mathematically the consequences of these assumptions as theoretical results. RESULTS: Under optimal supervision, (1) patient outcome is expected to be no worse than if residents were not involved, (2) supervisors will avoid undersupervising residents (when patients are at increased risk for poor outcomes) or oversupervising residents (when residents miss clinical opportunities to practice care), (3) optimal patient outcomes will be compatible with progressive independence, (4) progressive development can be inferred from progressive independence whenever residents contribute to patient care, and (5) analytic models that test for progressive independence will emphasize adjusting the association between length of graduate medical education training and supervision for case complexity and clinic workload, but not patient health outcomes. CONCLUSION: An explicit theoretical framework is critical to measure scientifically progressive independence from supervision using graduate medical education data. PMID- 21975880 TI - Measuring progressive independence with the resident supervision index: empirical approach. AB - BACKGROUND: A Resident Supervision Index (RSI) developed by our research team quantifies the intensity of resident supervision in graduate medical education, with the goal of testing for progressive independence. The 4-part RSI method includes a survey instrument for staff and residents (RSI Inventory), a strategy to score survey responses, a theoretical framework (patient centered optimal supervision), and a statistical model that accounts for the presence or absence of supervision and the intensity of patient care. METHODS: The RSI Inventory data came from 140 outpatient encounters involving 57 residents and 37 attending physicians during a 3-month period at a Department of Veterans Affairs outpatient clinic. Responses are scored to quantitatively measure the intensity of resident supervision across 10 levels of patient services (staff is absent, is present, participated, or provided care with or without a resident), case discussion (resident-staff interaction), and oversight (staff reviewed case, reviewed medical chart, consulted with staff, or assessed patient). Scores are analyzed by level and for patient care using a 2-part model (supervision initiated [yes or no] versus intensity once supervision was initiated). RESULTS: All resident encounters had patient care supervision, resident oversight, or both. Consistent with the progressive independence hypothesis, residents were 1.72 (P = .019) times more likely to be fully responsible for patient care with each additional postgraduate year. Decreasing case complexity, increasing clinic workload, and advanced nonmedical degrees among attending staff were negatively associated with supervision intensity, although associations varied by supervision level. CONCLUSIONS: These data are consistent with the progressive independence hypothesis in graduate medical education and offer empirical support for the 4 part RSI method to quantify the intensity of resident supervision for research, program evaluation, and resident assessment purposes. Before informing policy, however, more scientific research in actual teaching settings is needed to better understand the relationships among patient outcomes, clinic workload, case complexity, and graduate medical education experience in resident supervision and professional development. PMID- 21975881 TI - Disparity between resident and attending physician perceptions of intraoperative supervision and education. AB - BACKGROUND: As part of an ongoing evaluation of our residency program, a needs assessment was performed to assess resident and attending perspectives on current methods of surgical skills training in the operating room. METHODS: Participants included obstetrics-gynecology residents and faculty at a university program. Two surveys were developed and validated. Results were analyzed with 2-sample t tests, comparing Likert scores. Findings were significant if the difference between means was >1. RESULTS: Thirty of 31 residents and 40 of 60 attending physicians responded to the survey. Residents and attending physicians agreed that the surgical skills training program needs improvement (difference in mean, 0.39; confidence interval [CI]: -0.98 to 0.20). The areas of most disagreement were regarding feedback on surgical skills and instrument handling (difference in mean, 2.53; CI: 1.81-3.26, and difference in mean, 2.24; CI: 1.44-3.05). CONCLUSIONS: A significant proportion of surgical skills training during residency occurs as on-the-job training, and operating room time provides a key learning opportunity. This report demonstrates that there is a noteworthy difference in the perception of attending physicians and residents about the quality of teaching and feedback that is currently occurring in the operating room. The difference in perspectives among residents and attending physicians reported in this survey suggests a need for improved communication and systematic feedback in order to capitalize on operating room time as a critical surgical skills training arena. PMID- 21975882 TI - How residents view their clinical supervision: a reanalysis of classic national survey data. AB - BACKGROUND: Concerns over patient safety have made adequacy of clinical supervision an important component of care in teaching settings. Yet, few studies have examined residents' perceptions about the quality and adequacy of their supervision. We reanalyzed data from a survey conducted in 1999 to explore residents' perspectives on their supervision. METHODS: A national, multispecialty survey was distributed in 1999 to a 14.5% random sample of postgraduate year 2 (PGY-2) and PGY-3 residents. The response rate was 64.4%. Residents (n = 3604) were queried about how often they had cared for patients "without adequate supervision" during their preceding year of training. RESULTS: Of responding residents, 21% (n = 737) reported having seen patients without adequate supervision at least once a week, with 4.5% saying this occurred almost daily. Differences were found across specialties, with 45% of residents in ophthalmology, 46% in neurology, and 44% in neurosurgery stating that they had experienced inadequate supervision at least once a week throughout the year, compared with 1.5% of residents in pathology and 3% in dermatology. Inadequate supervision was found to be inversely correlated with residents' positive ratings of their learning, time with attendings, and overall residency experience (P < .001 for all), and positively correlated with negative features of training, including medical errors, sleep deprivation, stress, conflict with other medical personnel, falsifying patient records, and working while impaired (P < .001). CONCLUSIONS: In residents' self-report, inadequate clinical supervision correlates with other reported negative aspects of training. Collectively, this may detrimentally affect resident learning and patient safety. PMID- 21975883 TI - Strategies for effective on-call supervision for internal medicine residents: the superb/safety model. AB - BACKGROUND: Supervision is central to resident education and patient safety, yet there is little published evidence to describe a framework for clinical supervision. The aim of this study was to describe supervision strategies for on call internal medicine residents. METHODS: Between January and November 2006, internal medicine residents and attending physicians at a single hospital were interviewed within 1 week of their final call on the general medicine rotation. Appreciative inquiry and critical incident technique were used to elicit perspectives on ideal and suboptimal supervision practices. A representative portion of transcripts were analyzed using an inductive approach to develop a coding scheme that was then applied to the entire set of transcripts. All discrepancies were resolved via discussion until consensus was achieved. RESULTS: Forty-four of 50 (88%) attending physicians and 46 of 50 (92%) eligible residents completed an interview. Qualitative analysis revealed a bidirectional model of suggested supervisory strategies, the "SUPERB/SAFETY" model; an interrater reliability of 0.70 was achieved. Suggestions for attending physicians providing supervision included setting expectations, recognizing uncertainty, planning communication, having easy availability, reassuring residents, balancing supervision, and having autonomy. Suggested resident strategies for seeking supervision from attending physicians included seeking input early, contacting for active clinical decisions or feeling uncertain, end of life issues, transitions in care, or help with systems issues. Common themes suggested by trainees and attending physicians included easy availability and preservation of resident decision-making autonomy. DISCUSSION: Residents and attending physicians have explicit expectations for optimal supervision. The SUPERB/SAFETY model of supervision may be an effective resource to enhance the clinical supervision of residents. PMID- 21975884 TI - The effect of overnight in-house attending coverage on perceptions of care and education on a general medical service. AB - BACKGROUND: An increased emphasis on patient safety has led to calls for closer supervision of medical trainees. It is unclear what effect an increased degree of faculty presence will have on educational and clinical outcomes. The aim of this study was to evaluate resident and attending attitudes and preferences regarding overnight attending supervision. METHODS: This study was a cross-sectional electronic survey of physicians. Participants were resident and faculty physicians recently on inpatient service rotations after implementation of an overnight attending coverage system. RESULTS: Of 58 total respondents, most faculty (91%) and resident (92%) physicians reported they were satisfied with the overall quality of care delivered and believed the quality of care delivered overnight improved with an in-house attending system (90% and 85%, respectively). Most resident physicians (82%) believed the educational experience improved with the system of increased attending availability. Nearly all faculty (95%) and resident (97%) physicians preferred the in-house attending system to the traditional system of attendings being available by pager. The implementation of such coverage resulted in increased cost to the hospital for compensating covering hospitalist physicians. CONCLUSION: In-house attending coverage was acceptable to both residents and faculty, with perceived improvements in quality and educational experience. PMID- 21975885 TI - On-site Night Float by Attending Physicians: A Model to Improve Resident Education and Patient Care. AB - BACKGROUND: In 2003, the Accreditation Council for Graduate Medical Education instituted common duty hour limits, and in 2008 the Institute of Medicine recommended additional limits on continuous duty hours. Using a night-float system is an accepted approach for adhering to duty hour mandates. OBJECTIVE: To determine the effect of an on-site night-float attending physician on resident education and patient care. METHODS: Night-float residents and daytime ward residents were surveyed at the end of their rotation about the impact of an on site night-float attending physician on education and quality of patient care. Responses were provided on a 5-point Likert scale ranging from 1, strongly agree, to 5, strongly disagree. RESULTS: Overall, 92 of the 140 distributed surveys were completed (66% response rate). Night-float residents found the night-float attending physician to be helpful with cross-cover issues (mean = 2.00), initial history and physical examination (mean = 1.56), choosing appropriate diagnostic tests (mean = 1.79), developing a treatment plan (mean = 1.74), and improving overall patient care (mean = 1.91). Daytime ward residents were very satisfied with the quality of the admission workups (mean = 1.78), tests and diagnostic procedures (mean = 1.76), and initial treatment plan (mean = 1.62) provided by the night-float service. CONCLUSION: A night-float system that includes on-site attending physician supervision can provide a valuable opportunity for resident education and may help improve the quality of patient care. PMID- 21975886 TI - Patient-centered collaborative care: the impact of a new approach to postpartum rounds on residents' perception of their work environment. AB - OBJECTIVE: At our institution, traditional postpartum rounds consisted of separate visits from all members of the obstetric team. This led to patient care inefficiencies and miscommunication. In an effort to improve patient care, patient-centered collaborative care (PCCC) was established, whereby physicians, residents, medical students, nurses, case managers, and social workers conduct rounds as a team. The goal of this observational study was to evaluate how PCCC rounds affected resident physicians' assessment of their work environment. METHODS: Obstetrics and gynecology residents completed a 13-question written survey designed to assess their sense of workflow, education, and workplace cohesion. Surveys were completed before and 6 months after the implementation of PCCC. Responses were compared in aggregate for preintervention and postintervention with Pearson chi(2) test. RESULTS: Ninety-two percent of the obstetrics residents (n = 23) completed the preintervention survey, and 79% (n = 19) completed the postintervention survey. For most measures, there was no difference in resident perception between the 2 time points. After implementation of PCCC rounds, fewer residents felt that rounds were educational (preintervention = 39%, postintervention = 7%; P = .03). CONCLUSION: Residents did not report negative impacts on workflow, cohesion, or general well being after the implementation of PCCC rounds. However, there was a perception that PCCC rounds negatively impacted the educational value of postpartum rounds. This information will help identify ways to improve the resident physician experience in the obstetric service while optimizing patient care. PMID- 21975887 TI - A new approach to postpartum rounds: patient-centered collaborative care improves efficiency. AB - OBJECTIVE: At our institution, traditional postpartum rounds were time consuming and inefficient with a low percentage (approximately 12%) of patients meeting the goal of being discharged by 11:00 am. A patient-centered collaborative care (PCCC) initiative was implemented to improve discharge efficiency, staff communication, and patient satisfaction. We investigated whether this paradigm shift to PCCC could improve clinical inefficiencies and timely discharge. METHODS: The PCCC rounding system was created by a representative group of physicians, residents, nurses, case managers, and social workers. An intervention study was conducted to examine the impact of PCCC during which physicians, residents, medical students, nurses, case managers, and social workers made rounds together. Efficiency data were collected for patients whose infants were delivered by the obstetric service for a 1-month period before and 6 months after implementing PCCC. Comparisons were made on the time of discharge and whether Foley catheter removal affected discharge time. chi(2) test, Wilcoxon 2-sample test, and Pearson correlation coefficient were used where appropriate. RESULTS: Three hundred five patients were included in this analysis, of which 156 participated in traditional postpartum rounds and 149 in PCCC rounds. Discharge efficiency significantly improved with PCCC rounds, with 20.8% of patients being discharged by 11:00 am as compared to 11.5% for traditional postpartum rounds (P = .03). Early Foley catheter removal was significantly associated with time to discharge order (Pearson correlation coefficient, 0.22; P = .01) and discharge time (Pearson correlation coefficient, 0.28; P = .002). CONCLUSIONS: Patient centered collaborative care rounds improve the efficiency of postpartum care and discharge time. PMID- 21975888 TI - Balancing Knowledge Among Resident Specialties: Lecture-Based Training and the OUCH Card to Treat Children's Pain. AB - BACKGROUND: There are well-established deficiencies in residents' knowledge of acute-pain assessment and treatment in hospitalized children. METHODS: Among residents in 3 specialties (anesthesiology, orthopedics, and pediatrics), we investigated whether a pediatric pain management (PPM) curriculum that offered a lecture combined with a demonstration of how to use the OUCH card would yield higher performance on a subsequent PPM knowledge assessment. The OUCH card was created as a portable reference tool for trainees to provide analgesic dosing information, pain-assessment tools, and treatment of opioid-induced adverse effects. There was an initial convenience sample of 60 residents randomized to Form A or B of the pretest. From this, 39 residents (15 anesthesiology, 13 orthopedic, 11 pediatric) completed a PPM knowledge posttest approximately 4 weeks after the pretest, PPM lecture, and OUCH card instruction. RESULTS: Using a repeated measure design, the interaction of resident specialty and pretest to posttest scores was significant (P = .01) along with the covariate of residency year (P = .026). CONCLUSIONS: These preliminary data based on a convenience sample of residents suggest that PPM training along with use of the OUCH card may help to reduce knowledge differences among residents. Faculty whose clinical practice includes children with acute pain should consider including learning or performance aids like the OUCH card in education and clinical care for its potential benefit in resident learning. PMID- 21975889 TI - Teaching community pediatrics: a community resource fair for residents. AB - BACKGROUND: Pediatric residency programs are required to provide community and child advocacy experiences, but providing such community knowledge within the context of a busy, largely hospital-based training program can be challenging. OBJECTIVE: To assess the effectiveness of a community resource fair as a tool for increasing residents' knowledge of community-oriented care resources. DESIGN/METHODS: We organized a community resource fair for pediatrics and family medicine residents. Exhibitors (n = 31) represented a wide range of pediatric resources. An anonymous preassessment and postassessment was administered. RESULTS: Thirty-two trainees participated in the resource fair. On the basis of the preassessment, 62% (8 of 13) of the pediatrics residents reported that they had little or no knowledge about community resources, while 38% (5 of 13) were neutral; none felt somewhat or very knowledgeable. After the fair, 91% (10 of 11) of residents felt somewhat knowledgeable and 9% (1 of 11) felt very knowledgeable about community resources. Of the resident participants, 92% (12 of 13) found this to be a "worthwhile experience." CONCLUSIONS: The community resource fair provides an interactive format that brings residents and community organizations face-to-face to discuss what services are offered and how they can work together to coordinate patient care. PMID- 21975890 TI - A strategy to reduce interruptions at hospital morning report. AB - BACKGROUND: The learning atmosphere of hospital morning report is frequently interrupted by nonurgent beeper pages to participating residents. INTERVENTION: During 176 consecutive internal medicine morning reports, 1 of the 4 chief residents at a single academic medical center collected and answered house staff pages during the 30-minute conference. RESULTS: A total of 884 pages were answered during this period. Of these, 743 could wait until after the end of morning report, resulting in more than 4 interruptions averted per session. Over half of the pages were from nursing personnel. There was no significant decrease in the total number of pages or nurse pages during the observation period. DISCUSSION: In summary, our simple system of holding intern pages resulted in a dramatic reduction in interruptions during hospital morning report. PMID- 21975891 TI - An assessment tool for aseptic technique in resident physicians: a journey towards validation in the real world of limited supervision. AB - PURPOSE: The purpose of this study was to describe the validation process for assessing an instrument to assess residents' aseptic technique skills. METHODS: The validation study entailed comparisons of the performance of aseptic technique procedures between postgraduate year-1 (PGY-1) surgical residents and PGY-2/3 surgical residents. We also compared the performance of PGY-1 surgical residents from 2 different academic years for the same procedures. Finally, we compared the performance of novices (medical students) and experts (operating room nurses) in an effort to determine validity. RESULTS: Our initial analysis found no significant difference between the performance of PGY-1 (mean score, 75.8) and PGY-2/3 (mean score, 75.6) surgical residents for aseptic technique (t((55)) = 0.84, P = 0.404). Further investigation of validity was obtained to determine whether the no difference results reflected a lack of reliability or validity or a true equivalence between the 2 cohorts. The comparison of novices and experts produced the following findings. For reliability, the internal consistency of the checklist for each of the 2 raters was 0.87 and 0.71 (Cronbach alpha), interrater reliability was 0.74, with P < 0.001 (intraclass correlation coefficient) for the global scale. (Internal consistency was done within instrument, ie, between items not between raters.) For validity, operating room nurses outperformed students on the global scale (t(14) = 7.47, P < 0.0001 and t((14)) = 10.66, P < 0.0001 for the 2 raters, respectively) and on several checklist items. The effect size values for raters were large (Cohen d = 3.0 and 4.4), providing validity evidence for the ability of this assessment to detect difference in performance on this task. CONCLUSION: The validation study showed that the instrument exhibited reliability and evidence for validity, making it useful for the assesment of aseptic technique skills in different specialties. Programs may want to consider using a validated instrument to check competence given that appropriate use of sterile technique frequently occurs in the context of unsupervised activities. Further work is needed to enhance resident skills in the area of aspectic technique because of limited improvement despite additional clinical experience. PMID- 21975892 TI - Using the american board of internal medicine practice improvement modules to teach internal medicine residents practice improvement. AB - BACKGROUND: Although residency programs must prepare physicians who can analyze and improve their practice, practice improvement (PI) is new for many faculty preceptors. We describe the pilot of a PI curriculum incorporating a practice improvement module (PIM) from the American Board of Internal Medicine for residents and their faculty preceptors. METHODS: Residents attended PI didactics and completed a PIM during continuity clinic and outpatient months working in groups under committed faculty. RESULTS: All residents participated in PI group projects. Residents agreed or strongly agreed that the projects and the curriculum benefited their learning and patient care. A self-assessment revealed significant improvement in PI competencies, but residents were just reaching a "somewhat confident" level. CONCLUSION: A PI curriculum incorporating PIMs is an effective way to teach PI to both residents and faculty preceptors. We recommend the team approach and use of the PIM tutorial approach especially for faculty. PMID- 21975893 TI - Using the cross-cultural care survey to assess cultural competency in graduate medical education. AB - BACKGROUND: Cultural competency is an important part of medical policy and practice, yet the evidence base for the effectiveness of training in this area is weak. One reason is the lack of valid, reliable, and feasible tools to quantify measures of knowledge, skill, and attitudes before and/or after cultural training. Given that cultural competency is a critical aspect of "professionalism" and "interpersonal and communication skills," such a tool would aid in assessing the impact of such training in residency programs. OBJECTIVES: The aim of this study is to enhance the feasibility and extend the validity of a tool to assess cultural competency in resident physicians. The work contributes to efforts to evaluate resident preparedness for working with diverse patient populations. METHOD: Eighty-four residents (internal medicine, psychiatry, obstetrics-gynecology, and surgery) completed the Cross-Cultural Care Survey (CCCS) to assess their self-reported knowledge, skill, and attitudes regarding the provision of cross-cultural care. The study entailed descriptive analyses, factor analysis, internal consistency, and validity tests using bivariate correlations. RESULTS: Feasibility of using the CCCS was demonstrated with reduced survey completion time and ease of administration, and the survey reliably measures knowledge, skill, and attitudes for providing cross-cultural care. Resident characteristics and amount of postgraduate training relate differently to the 3 different subscales of the CCCS. CONCLUSIONS: Our study confirmed that the CCCS is a reliable and valid tool to assess baseline attitudes of cultural competency across specialties in residency programs. Implications of the subscale scores for designing training programs are discussed. PMID- 21975894 TI - Contextualizing SEGUE: Evaluating Residents' Communication Skills Within the Framework of a Structured Medical Interview. AB - BACKGROUND: The SEGUE (Set the stage, Elicit information, Give information, Understand the patient's perspective, and End the encounter) Framework is a checklist-style rating scale to facilitate the teaching and assessment of communication skills in medical learners. It has been used for over 15 years, and it is recommended in the Accreditation Council for Graduate Medical Education toolbox of assessment methods for resident training. When it was developed, its ability to provide objective scoring was a substantial improvement over global ratings. METHODS: In this article we describe the strengths and weaknesses of the SEGUE Framework. We highlight one residency program's experience with using the SEGUE Framework to evaluate residents' communication skills. Specifically, we cite previous studies and describe our own analysis of resident interviewing performance that demonstrates how the SEGUE Framework did not distinguish between different levels of interviewing skill level in our sample. RESULTS: Two case examples illustrate how the SEGUE Framework is not an ideal instrument to measure either the quality or the process of medical interviews. CONCLUSION: Therefore, we propose a new method of contextualized assessment that builds on the SEGUE Framework. Our system evaluates discrete interviewing behaviors within the context of an ambulatory medical interview. We describe our interview structure, as well as a new instrument (the Wy-Mii, pronounced "why me"), to assess both communication and interpersonal skills. We expect that our new method of contextualized assessment will better differentiate between beginning and advanced levels of medical interviewing skills for residents. PMID- 21975895 TI - A simplified observation tool for residents in the outpatient clinic. AB - BACKGROUND: The Accreditation Council for Graduate Medical Education promotes direct observation of residents as a key assessment tool for competency in patient care, professionalism, and communication skills. Although tools exist, validity and reliability have not been demonstrated for most, and many tools may have limited feasibility because of time constraints and other reasons. We conducted a study to measure feasibility of a simplified observation tool to evaluate these competencies and provide timely feedback. METHODS: In the pediatric resident continuity clinic of a large children's hospital, we used a direct observation form with a 3-point scale for 16 items in the domains of patient care, professionalism, and communication skills. The form was divided by portion of visit, with specific items mapped to 1 or more of the competencies, and was used to provide direct oral feedback to the resident. Faculty and residents completed surveys rating the process (ease of use, satisfaction, and self-assessed usefulness) on a 5-point Likert scale. RESULTS: The study encompassed 89 surveys completed by attending physicians; 98% (87 of 89) of the time the form was easy to use, 99% (88) of the time its use did not interfere with patient flow, and 93% (83) of the observations provided useful information for resident feedback. Residents completed 70 surveys, with the majority (69%, 48) reporting they were comfortable about being observed by an attending physician; 87% (61) thought that direct observation did not significantly affect their efficiency. Ninety-seven percent of the time (68) residents reported that direct observation provided useful feedback. CONCLUSION: The data suggest the form was well-received by both faculty and residents, and enabled attending physicians to provide useful feedback. PMID- 21975896 TI - Use of a standardized patient exercise to assess core competencies during fellowship training. AB - BACKGROUND: The Accreditation Council for Graduate Medical Education requires fellows in many specialties to demonstrate attainment of 6 core competencies, yet relatively few validated assessment tools currently exist. We present our initial experience with the design and implementation of a standardized patient (SP) exercise during gastroenterology fellowship that facilitates appraisal of all core clinical competencies. METHODS: Fellows evaluated an SP trained to portray an individual referred for evaluation of abnormal liver tests. The encounters were independently graded by the SP and a faculty preceptor for patient care, professionalism, and interpersonal and communication skills using quantitative checklist tools. Trainees' consultation notes were scored using predefined key elements (medical knowledge) and subjected to a coding audit (systems-based practice). Practice-based learning and improvement was addressed via verbal feedback from the SP and self-assessment of the videotaped encounter. RESULTS: Six trainees completed the exercise. Second-year fellows received significantly higher scores in medical knowledge (55.0 +/- 4.2 [standard deviation], P = .05) and patient care skills (19.5 +/- 0.7, P = .04) by a faculty evaluator as compared with first-year trainees (46.2 +/- 2.3 and 14.7 +/- 1.5, respectively). Scores correlated by Spearman rank (0.82, P = .03) with the results of the Gastroenterology Training Examination. Ratings of the fellows by the SP did not differ by level of training, nor did they correlate with faculty scores. Fellows viewed the exercise favorably, with most indicating they would alter their practice based on the experience. CONCLUSIONS: An SP exercise is an efficient and effective tool for assessing core clinical competencies during fellowship training. PMID- 21975897 TI - The Associations Between Residents' Behavior and the Thomas-Kilmann Conflict MODE Instrument. AB - OBJECTIVE: To assess if the Thomas-Kilmann Conflict MODE Instrument predicts residents' performance. STUDY DESIGN: Nineteen residents were assessed on the Thomas-Kilmann conflict modes of competing, collaborating, compromising, accommodating, and avoiding. Residents were classified as contributors (n = 6) if they had administrative duties or as concerning (n = 6) if they were on remediation for academic performance and/or professionalism. Data were compared to faculty evaluations on the Accreditation Council for Graduate Medical Education (ACGME) competencies. P value of < .05 was considered significant. RESULTS: Contributors had significantly higher competing scores (58% versus 17%; P = .01), with lower accommodating (50% versus 81%; P 5 .01) and avoiding (32% versus 84%; P = .01) scores; while concerning residents had significantly lower collaborating scores (10% versus 31%; P = .01), with higher avoiding (90% versus 57%; P = .006) and accommodating (86% versus 65%; P = .03) scores. There were significant positive correlations between residents' collaborating scores with faculty ACGME competency evaluations of medical knowledge, communication skills, problem-based learning, system-based practice, and professionalism. There were also positive significant correlations between compromising scores and faculty evaluations of problem-based learning and professionalism with negative significant correlations between avoiding scores and faculty evaluations of problem-based learning, communication skills and professionalism. CONCLUSIONS: Residents who successfully execute administrative duties are likely to have a Thomas-Kilmann profile high in collaborating and competing but low in avoiding and accommodating. Residents who have problems adjusting are likely to have the opposite profile. The profile seems to predict faculty evaluation on the ACGME competencies. PMID- 21975898 TI - Immediate impact of participation in the electronic residency application service on a fellowship program. AB - OBJECTIVE: This study sought to evaluate the immediate impact of participation in the Electronic Residency Application Service (ERAS) on a single cardiology fellowship program. METHOD: The study reviewed all applications (n = 1824) made to the Geisinger Medical Center cardiology fellowship program over a 4-year period (2004-2007). The aggregate data for the first 2 years (pre-ERAS, 2004 and 2005) was compared to that of the last 2 years (post-ERAS, 2006 and 2007). RESULTS: Compared to the pre-ERAS period, the total number of applications in the post-ERAS period increased by 49% (732 versus 1092; p<.05) and the number of complete applications increased by 70% (577 versus 983; p<.05). Other significant differences (p<.05) included a higher percentage of applications from female candidates (81 of 732 [11%] versus 186 of 1092 [17%]), and a greater geographic distance from applicants' internal medicine residency institutions (420 +/- 454 miles versus 585 +/- 559 miles]. Comparison of applicants' age, citizenship status, graduation origin, years since medical school graduation, and United States Medical Licensing Examination scores yielded no significant differences between pre-ERAS and post-ERAS periods. CONCLUSION: Participation in ERAS resulted in an immediate increase in the total number of applications, higher proportion of applications with complete data, a higher number and proportion of female applicants, and a wider geographic distribution of applications. This likely reflects ease of application submission through a central electronic service. However, the administrative burden on fellowship programs and the effects of wider geographic distribution of applications on the fellowship matching process merit further evaluation. PMID- 21975899 TI - Developing a predictive model to assess applicants to an internal medicine residency. AB - BACKGROUND: Residency programs strive to accurately assess applicants' qualifications and predict future performance. However, there is little evidence based guidance on how to do this. The aim of this study was to design an algorithm for ranking applicants to an internal medicine residency program. METHODS: Ratings of overall performance in residency were compared to application characteristics of 230 graduating residents from 2000-2005. We analyzed 5 characteristics of the application: medical school, overall medical school performance, performance in junior medicine clerkship, United States Medical Licensing Examination (USMLE) Step 1 score, and interview ratings. Using bivariate correlations and multiple regression analysis, we calculated the association of each characteristic with mean performance ratings during residency. RESULTS: In multiple regression analysis, the most significant application factors (r(2) = 0.22) were the quality of the medical school and the applicant's overall performance in medical school (P < .001). CONCLUSION: This data has allowed the creation of a weighted algorithm to rank applicants that uses 4 application factors-school quality, overall medical school performance, medicine performance, and USMLE Step 1 score. PMID- 21975900 TI - Efficacy and efficiency of webcast orientations versus live resident orientations: results of a 2-year survey. AB - BACKGROUND: Beginning a graduate medical education training program is associated with a steep learning curve for incoming residents. OBJECTIVE: To compare the efficacy and efficiency of live versus webcast formats for Institutional Orientation. METHODS: This 2-year non-blinded study, with a nonrandomized cohort, compares outcomes for trainees oriented Summer 2005 in a ''live-lecture'' format with trainees oriented Summer 2006 using a webcast format. Outcomes include posttest success, the time required, presentation quality and utility, and cost. RESULTS: In 2005, 249 trainees attended the live orientation. Of the 211 who completed the posttest; 132 (63%) passed it within 3 attempts. Of the 241 trainees in 2006, 236 completed the posttest. Of these, 215 (91%) passed it within 3 attempts. Compared to the live-lecture cohort, the webcast cohort rated the posttest as more difficult. Despite performing better, significantly fewer trainees in the webcast cohort rated the posttest as "appropriate" (chi(2) = 5 28.57, df 5 1, P , .001). There were no significant differences between the 2 groups on their perceptions of quality and utility of the presentations. While the first year cost of the webcast exceeded that of live lectures, the amortized cost was nearly identical to the live-lecture costs. DISCUSSION: As corroborated by resident comments, the web-based approach was more effective because it provided trainees flexibility regarding when to study, options on how to view the material, and opportunities to review it if needed for mastery. We plan to continue using the webcast strategy, revising the content as needed. PMID- 21975901 TI - Supervision in medical education: logical fallacies and clear choices. PMID- 21975902 TI - Supervision, preoccupation with failure, and the cultural shift in patient handover. PMID- 21975905 TI - [Reconstruction of extended defects of the Achilles tendon using a flexor hallucis longus tendon transfer.] AB - OBJECTIVE: The aim of flexor hallucis longus (FHL) transfer is to bridge long defects of the Achilles tendon. In addition to the substitution of the Achilles tendon by the tendon graft, the flexor hallucis longus muscle changes its function to plantar flexion of the ankle. A part of the muscle belly is placed into the paratendon sheath which supports healing even in patients with critical soft tissue injuries. INDICATIONS: Extended Achilles tendon defects, extended degenerative disease of the Achilles tendon, and reruptures, especially in patients with significant soft tissue injuries. CONTRAINDICATIONS: Ruptures of the Achilles tendon which can be treated by direct reconstruction. SURGICAL TECHNIQUE: The patient is placed in a prone position. After a central longitudinal approach to the Achilles tendon and debridement of the diseased tendon material, the deep fascia is split. After identification of the flexor hallucis longus tendon, the tendon is retracted with a plantiflexed hallux and dissected at the entrance point to the tarsal tunnel. The tendon is fixed to the calcaneus via a 6 mm drill hole using an interference screw in the press-fit technique. POSTOPERATIVE MANAGEMENT: A lower limb orthosis is used for the first 8 weeks: the first 4 weeks plantar flexion of 30 degrees with partial weight bearing of 20 kg, then full weight bearing for 2 weeks with 15 degrees plantar flexion, and another 2 weeks with neutral position of the ankle. After removal of the orthosis, a heel lift of 1.5 cm (e.g., silicon heel cushion) is recommended for 3 months. Running activities are restricted for 6 months. RESULTS: In a series of 25 consecutive patients (15 men, 10 women) with an average age of 61 years (range 37-79 years), it was possible in all cases to reconstruct the Achilles tendon function. The AOFAS Hindfoot Score improved from 62 to 89 points. Especially in the category pain, the patients reached 38 of a maximum of 40 points. Compared to the healthy leg, a limitation in maximum strength in plantar flexion was found (42 of a maximum of 50 points). PMID- 21975906 TI - [Arthroscopic filling of misplaced and wide bone tunnels after reconstruction of the anterior cruciate ligament with bone graft in patients with recurrent instability.] AB - OBJECTIVE: Arhroscopically performed autologous bone grafting of the femoral or tibial tunnel after anterior cruciate ligament (ACL) reconstruction in symptomatic anterior knee instability. INDICATIONS: Subjective and objective instability in cases with recurrent instability following ACL reconstruction with tibial or femoral tunnel malplacement and tunnel widening. CONTRAINDICATIONS: Open growth plates, severe osteoarthritic changes. SURGICAL TECHNIQUE: Arthroscopic ACL graft resection and implant removal followed by debridement of the tunnel and the sclerotic tunnel walls. Cortical bone cylinders and cancellous bone grafts are harvested from the iliac crest and transplanted into the enlarged and malplaced tunnels. The harvest site may be filled with bone substitutes. RESULTS: Arthroscopic filling of malplaced or enlarged bone tunnels was performed in 42 patients (14 men, 28 women, age range 18-37 years) with recurrent instability after ACL reconstruction. All patients presented with tunnel malplacement, while 38 patients also had tunnel widening. In 39 cases, a tibial bone graft was necessary; in 12 cases the femoral defect was filled with autologous bone. No complications, such as hematomas of infections, were observed. CT scans showed complete integration of the osseous grafts after 3-6 months. PMID- 21975907 TI - [Upper leg amputation. Transfemoral amputation]. AB - Objective. Amputation through the diaphysis of the femur at the most peripheral level possible. The stump, covered with soft tissue flaps, is free from pain. It can be fitted with a total contact prosthetic socket. The hip joint is preserved with its full range of motion.Indications. When no possibility to amputate at a more distal level through the tibia or the knee joint exists.Contraindications. When it is possible to amputate at a more distal level.Surgical technique. Symmetrical flaps in the frontal plane are recommended. Asymmetrical flaps and flaps in the sagittal plane can also be made. Their muscles are fixed to each other (myodesis) or the bone end by means of transosseous sutures (myopexy). The ischial nerve has to be shortened about 2 inches proximal to the end of the femur.In peripheral vascular diseases, this procedure is not suitable. An alternative technique is suggested.In chronic osteomyelitis (e.g., after intramedullary nailing), the ventral half of the femur can be removed and the medullary cavity cleansed and filled with a muscular flap in order to maintain length. Lengthening procedures of the femur are discussed.Postoperative management. Avoid active or passive movement of the stump for the first 2 weeks in order not to disturb healing of the muscle sutures. Physical therapy, prosthetic fitting after 4-6 weeks, according to the expected functional level 0 4. Aids: crutches, wheel chair, adjustable bed, modified hand-controlled automobile.The walking ability of a patient with a double amputation above the knee is severely limited and in patients with peripheral artery disease remains the exception. PMID- 21975908 TI - Facile synthesis of Ag@Pd satellites-Fe3O4 core nanocomposites as efficient and reusable hydrogenation catalysts. AB - Well-dispersed Ag@Pd supported on magnetite nanoparticles have been obtained through a simple colloidal impregnation method. The as-synthesised nanocomposite exhibits greatly enhanced catalytic reactivity and reusability towards 4 nitrophenol hydrogenation. PMID- 21975910 TI - Pulmonary neuroendocrine carcinomas: progress and pitfalls. PMID- 21975909 TI - A one-pot synthesis of 7-phenylindolo[3,2-a]carbazoles from indoles and beta nitrostyrenes, via an unprecedented reaction sequence. AB - A six-step one-pot reaction was designed for synthesizing homodimeric 7 phenylindolo[3,2-a]carbazoles from 1H-indoles and beta-nitrostyrenes, in the presence of SnCl(2).2H(2)O. The reactions proceeded under very mild conditions and the desired heterocycles were obtained in moderate to good yields. An unprecedented mechanism involving sequential indole dimerization, regioselective nucleophilic conjugate addition of the resulting 2,3'-biindole to beta nitrostyrene and formal intramolecular [4 + 2]-cycloaddition is proposed. PMID- 21975911 TI - Small cell lung cancer. PMID- 21975912 TI - Large-cell neuroendocrine carcinoma: controversies in diagnosis and treatment. AB - The diagnosis and treatment of large cell neuroendocrine carcinoma are controversial, difficult, and clearly still evolving. Diagnosing this particular entity can be hampered by the limitations and restrictions imposed by its own definition in the current WHO classification. These complexities in the semantics of diagnostic criteria can puzzle not only the pathologist but also the treating physician, and lead to difficulties in choosing treatment for individual patients. Because of its low incidence (2%-3% of non-small cell carcinomas) and the difficulties in diagnosis, data regarding treatment outcomes are based on series in which the diagnosis is frequently made retrospectively in reclassification, the numbers of patients are small, and the determinants of therapy choice (e.g., treatment with or without adjuvant chemotherapy postresection) cannot be known. Thus, the evidence on which to base recommendations for stage-based treatment paradigms is flawed in many respects. This article discusses these difficult issues for pathologists and oncologists, offers a perspective regarding approaches in treatment, and suggests ways in which prospective data on this uncommon cancer can be gathered to inform treatment guidelines and improve patient outcomes. PMID- 21975913 TI - Surgery for early-stage small cell lung cancer. AB - Limited-stage small cell lung cancer remains one of the more frustrating malignancies to treat. Current standard of care typically includes platinum-based chemotherapy with thoracic radiation, and although response to therapy is high, most patients will ultimately experience relapse and die of recurrent disease. No high-level data exist supporting surgical resection of early-stage disease; however, several retrospective reviews and small single-arm studies suggest surgery may benefit patients with very limited extent of disease. This article reviews the available literature, and proposes guidelines for including potentially curative resection in the management of patients with limited-stage small cell lung cancer. PMID- 21975914 TI - Multiple myeloma. PMID- 21975915 TI - Evolving paradigms in the treatment of newly diagnosed multiple myeloma. AB - The treatment of multiple myeloma has undergone significant changes in the past few years. The introduction of novel agents, such as the immunomodulatory drugs thalidomide and lenalidomide and the proteasome inhibitor bortezomib, has dramatically improved the outcome of this disease and considerably increased the treatment options available. Several trials have shown the advantages linked to the use of novel agents both in young patients, who are considered eligible for transplantation, and elderly patients, for whom a conventional therapy should be considered. These novel agents may increase the efficacy of autologous stem cell transplantation with deeper and long-lasting response. In the transplant setting, different novel agent combinations have proved to be superior to the traditional vincristine-doxorubicin-dexamethasone. Similarly, novel agents have also changed the treatment paradigm of patients not eligible for transplantation, thus replacing the traditional melphalan-prednisone approach. Preliminary data also support the role of consolidation and maintenance therapy to further improve outcomes. This article provides an overview of the latest strategies, including novel agents used to treat patients with multiple myeloma, both in the transplant and nontransplant settings. PMID- 21975916 TI - The impact of genomics on the management of myeloma. AB - Myeloma is a complex disease, characterized by a wide heterogeneity in clinical presentation, evolution, and molecular portraits. The successive use of cytogenetics, molecular cytogenetics, expression genomics, copy number genomics, and, more recently, deep sequencing, has shown that this heterogeneity can be used to identify markers usable for not only prognostication but also therapeutic choice and, ultimately, discovery of druggable targets. The use of some of these techniques is now mandatory for the management of patients. Although risk-adapted therapy is not yet a routine practice in myeloma, these molecular changes are essential for the definition of the prognosis. PMID- 21975917 TI - Management of relapsed and relapsed/refractory multiple myeloma. AB - Despite significant progress in the treatment of multiple myeloma (MM) over the past decade, this disease remains incurable and almost all patients ultimately experience relapse and become refractory to treatment over time. However, the outlook for patients with relapsed MM has improved markedly with the use of the immunomodulatory drugs thalidomide and lenalidomide, and the proteasome inhibitor bortezomib. Moreover, the development of new drug classes based on preclinical rationale and the introduction of next-generation agents is likely to further expand treatment options and improve outcomes for relapsed MM. PMID- 21975919 TI - Effects of eicosapentaenoic acid versus docosahexaenoic acid on serum lipids: a systematic review and meta-analysis. AB - Omega-3 fatty acid supplements containing both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to reduce triglycerides but also increase low-density lipoprotein (LDL). Whether EPA or DHA given as monotherapy has differential effects on serum lipoproteins has not been systematically evaluated. We performed a meta-analysis of randomized placebo-controlled trials of monotherapy with EPA (n=10), DHA (n=17), or EPA versus DHA (n=6). Compared with placebo, DHA raised LDL 7.23 mg/dL (95% CI, 3.98-10.5) whereas EPA non significantly reduced LDL. In direct comparison studies, DHA raised LDL 4.63 mg/dL (95% CI, 2.15-7.10) more than EPA. Both EPA and DHA reduced triglycerides, with a greater reduction by DHA in direct comparison studies. DHA also raised high-density lipoprotein (4.49 mg/dL; 95% CI, 3.50-5.48) compared with placebo, whereas EPA did not. Although EPA and DHA both reduce triglycerides, they have divergent effects on LDL and high-density lipoprotein. Further research is needed to elucidate the mechanisms and significance of these differences. PMID- 21975920 TI - Sexual hookups among college students: sex differences in emotional reactions. AB - The purpose of the study was to test four predictions derived from evolutionary (sexual strategies) theory. The central hypothesis was that men and women possess different emotional mechanisms that motivate and evaluate sexual activities. Consequently, even when women express indifference to emotional involvement and commitment and voluntarily engage in casual sexual relations, their goals, their feelings about the experience, and the associations between their sexual behavior and prospects for long-term investment differ significantly from those of men. Women's sexual behavior is associated with their perception of investment potential: long-term, short-term, and partners' ability and willingness to invest. For men,these associations are weaker or inversed. Regression analyses of survey data from 333 male and 363 female college students revealed the following: Greater permissiveness of sexual attitudes was positively associated with number of sex partners; this association was not moderated by sex of subject (Prediction 1); even when women deliberately engaged in casual sexual relations, thoughts that expressed worry and vulnerability crossed their minds; for females, greater number of partners was associated with increased worry-vulnerability whereas for males the trend was the opposite (Prediction 2); with increasing numbers of sex partners, marital thoughts decreased; this finding was not moderated by sex of subject; this finding did not support Prediction 3; for both males and females, greater number of partners was related to larger numbers of one-night stands, partners foreseen in the next 5 years, and deliberately casual sexual relations. This trend was significantly stronger for males than for females (Prediction 4). PMID- 21975921 TI - Female breast size attractiveness for men as a function of sociosexual orientation (restricted vs. unrestricted). AB - Mate preferences are context-dependent and may vary with different ecological conditions and raters. The present study investigated whether sociosexual orientation influenced men's rating of attractiveness of female breast size. Participants (N=128) rated female breast attractiveness as a function of size (five levels) and viewing angles (front view, oblique view, and side view). Men were divided into two groups (restricted and unrestricted), based on their responses to the Revised Sociosexual Orientation Inventory (SOI-R). As predicted, men with higher SOI-R scores (unrestricted) generally gave higher ratings than did men who scored lower on the SOI-R(restricted), but the difference was significant only at larger breast sizes. We also found that medium to large sizes were rated as the most attractive by both male groups and that viewing angle changed rating of female attractiveness and breast presented in oblique view were rated generally higher than in side view. The results of the study indicate that sociosexuality influences male perception of female breast attractiveness and confirm that accentuation of female-specific physical traits produces a stronger response in unrestricted than in restricted men. PMID- 21975922 TI - Early maladaptive schemas and sexual dysfunction in men. AB - The objective of the present study was to investigate the role played by early maladaptive schemas (EMS) on male sexual functioning and clarify the way these nuclear cognitive structures discriminate men with and without sexual dysfunction. A total of 242 men participated in the study (a community sample of 200 men and a clinical sample of 42 men with a DSM-IV diagnosis of sexual dysfunction). The community sample was divided into a control group (n=147) and a sub-clinical group (n=53), according to the cutoff scores of the International Index of Erectile Dysfunction (Rosen et al., 1997). All participants completed a set of measures assessing EMS (Young & Brown, 1989), sexual functioning (Rosen et al., 1997), psychopathology (Derogatis & Spencer, 1982), and cognitive schemas activated in hypothetical unsuccessful sexual situations (Nobre & Pinto-Gouveia, 2009a). Findings supported the hypothesis of a typical cognitive pattern in men with sexual difficulties. After controlling for psychopathology, men with sexual dysfunction reported more dependence/incompetence EMS and activated more difference, helpless, and particularly incompetence schemas in hypothetical unsuccessful sexual situations, in comparison to sexually healthy men. These results have important therapeutic implications for sex therapy. PMID- 21975923 TI - Prevalence of same-sex behavior and orientation in England: results from a national survey. AB - There are few data sources on the prevalence of same-sex sexual orientation in England.We aimed to measure the prevalence of same-sex orientation and behavior in the English general population and assess the impact of enquiry format on reporting. The Adult Psychiatric Morbidity Survey 2007 used a multi-stage, stratified probability-sampling design (n=7,403). Two questions addressed sexual orientation and sexual partnership and each had two versions. Version A of the sexual orientation question used "homosexual." Version B used "gay or lesbian." Version A of the sexual partnership question required participants who had male and female partners to say which was predominant, while Version B had a midpoint response option: "about equally with men and women." Participants were randomized between versions. Overall, 5.3% of men and 5.6%of women reported they were not entirely heterosexual. The question using "gay or lesbian" elicited higher (though not statistically significant) reporting of non-heterosexual orientation than the question using "homosexual." A significantly larger proportion of men and women (96.0 and 96.1%) reported entirely heterosexual partnerships in response to Version A of the partnership question than in response to Version B (94.0 and 92.9%) where Version B asked specifically about "kissing, touching, intercourse, or any other form of sex." These figures constitute the first national prevalence data on combined sexual orientation and sexual behavior in England, based on a random probability sample of the general population. They demonstrate that people are willing to report their sexual orientation in survey research, but reporting is sensitive to question wording. PMID- 21975924 TI - The costs of rape. AB - The current study examined costs experienced by victims of completed rape (n=49) and attempted sexual assault (n=91) using quantitative analyses of 13 domains: health, self-esteem, self-perceived attractiveness, self-perceived mate value, family relationships,work life, social life, social reputation, sexual reputation, desire to have sex, frequency of sex, enjoyment of sex, and long term, committed relationships. Women also provided descriptive accounts of their experiences, and we used these to illustrate the costs in the victims' own words.Compared to victims of an attempted sexual assault, victims of a completed rape reported significantly more negative outcomes in 11 of the 13 domains. The most negatively affected domains were self-esteem, sexual reputation, frequency of sex, desire to have sex, and self-perceived mate value. Although victims of rape experienced more negative effects than victims of attempted sexual assault,both groups of victims reported negative effects in every domain.Discussion focuses on the implications of the differing degrees and patterns of the costs of attempted and completed sexual victimization. PMID- 21975925 TI - Efficacy of cilostazol for intracranial arterial stenosis evaluated by digital subtraction angiography/magnetic resonance angiography. AB - INTRODUCTION: Intracranial arterial stenosis is an important factor in the development of cerebral infarction; however, no effective treatment has been established. A phosphodiesterase 3 (PDE3) inhibitor, cilostazol, has been reported to suppress progression of symptomatic intracranial arterial stenosis in combination with aspirin, but the study used magnetic resonance angiography (MRA) for evaluation, which is not considered optimal for assessment of stenotic lesions. METHODS: A preliminary study was conducted to investigate the efficacy of cilostazol using MRA and intra-arterial digital subtraction angiography (DSA). DSA was performed in 18 patients for whom intracranial arterial stenosis was suspected from MRA. Cilostazol (200 mg/day) was administered orally for 1 year to 13 patients with 16 lesions (nine symptomatic, seven asymptomatic) confirmed by DSA. MRA and DSA were repeated at 6 and 12 months. RESULTS: Through MRA at 6 and 12 months, regression was observed in nine (56.3%) and eight (50.0%) patients, six (37.5%) and seven (43.8%) patients remained stationary, and one (6.3%) and one (6.3%) patient progressed, respectively. From DSA, percent stenosis for all lesions significantly improved from 49.2 (+/-15.4%) to 42.6 (+/-12.7%) at 12 months (P=0.023). In nine symptomatic lesions, stenosis was 55.3 (+/-7.3%) at baseline, 46.3 (+/-12.5%) at 6 months (P=0.029), and 47.7 (+/-9.9%) at 12 months (P=0.049). In contrast, in seven asymptomatic lesions, no significant improvement was observed at 6 months (P=0.113) or 12 months (P=0.157). When evaluated by severity, there was a significant improvement in 11 lesions with >=50% stenosis, but no significant improvement was observed in five lesions with <50% stenosis. No patient developed symptomatic stroke events. CONCLUSION: Cilostazol may induce improvement of symptomatic intracranial arterial stenosis or severe lesions. A combination of MRA and DSA might be another diagnostic option for more precise examination. PMID- 21975926 TI - Pharmacokinetic pilot study of the antiangiogenic activity of standardized platycodi radix. AB - INTRODUCTION: Platycodi radix is a radish used in food, such as Korean kimchi, and has been shown to cause weight loss in rodents. Platycodin D is considered its active ingredient and has been shown to inhibit lipases. The authors hypothesized that platycodi radix and the platycodin D it contains inhibit angiogenesis; another mechanism for weight loss. METHODS: This study tested platycodi radix extract, platycodin D, and an extract of platycodi radix standardized to platycodin D for their ability to inhibit angiogenesis in a human adipose tissue assay. This study treated five healthy volunteers, orally, with platycodi radix extract standardized to 414 mg of platycodin D. Three volunteers were treated under fasting conditions, one volunteer with a 400 kcal meal, and one volunteer treated with a placebo. Blood was drawn over 5 hours to compare serum inhibition of the human adipose tissue angiogenesis. RESULTS: Platycodin radix extract, platycodin D, and platycodi radix extract standardized to platycodin D all inhibited angiogenesis. The three volunteers who consumed platycodi radix extract standardized to 414 mg of platycodin D had a 25.76% reduction in angiogenesis from baseline at 60 minutes (P<0.002), and had a statistically significant reduction in angiogenesis from 30 to 240 minutes (P<0.05 to P<0.002). The placebo decreased angiogenesis by 5.6% between 30 and 240 minutes, compared with 17.8% by the extract. The meal delayed absorption by approximately 3.5 hours. CONCLUSION: Platycodi radix extract standardized to platycodin D inhibited angiogenesis in human volunteers, and paves the way for a dose-response study and a human clinical obesity trial. PMID- 21975927 TI - Idiopathic pulmonary fibrosis: treatment update. AB - Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. Despite multiple recent clinical trials, there is no strong evidence supporting a survival advantage for any agent in the management of patients with IPF. The limited effectiveness of current treatment regimes has led to a search for novel therapies including antifibrotic strategies. This article reviews the evidence supporting the treatments currently used in the management of IPF. PMID- 21975928 TI - Highly effective synthesis and photoluminescence of Sr2Si5N8:Eu2+ red-emitting phosphor for LEDs. AB - We developed a highly effective and self-sustaining route for synthesizing Sr(2)Si(5)N(8):Eu(2+) red-emitting phosphor particles for use in light emitting diodes (LEDs). The phosphors thus synthesized showed excellent emission characteristics under a blue excitation wavelength of 450 nm, had a uniform particle size distribution, and showed high performance in LED packages. PMID- 21975929 TI - Chemotherapy enhances metastasis formation via VEGFR-1-expressing endothelial cells. AB - Recent studies suggest that chemotherapy, in addition to its cytotoxic effects on tumor cells, can induce a cascade of host events to support tumor growth and spread. Here, we used an experimental pulmonary metastasis model to investigate the role of this host response in metastasis formation. Mice were pretreated with chemotherapy and after clearance of the drugs from circulation, tumor cells were administered intravenously to study potential "protumorigenic" host effects of chemotherapy. Pretreatment with the commonly used chemotherapeutic agents cisplatin and paclitaxel significantly enhanced lung metastasis in this model. This corresponded to enhanced adhesion of tumor cells to an endothelial cell monolayer that had been pretreated with chemotherapy in vitro. Interestingly, chemotherapy exposure enhanced the expression of VEGF receptor 1 (VEGFR-1) on endothelial cells both in vitro and in vivo. Administration of antibodies targeting VEGFR-1 reversed the early retention of tumor cells in the lungs, thereby preventing the formation of chemotherapy-induced pulmonary metastases. The data indicate that chemotherapy-induced expression of VEGFR-1 on endothelial cells can create an environment favorable to tumor cell homing. Inhibition of VEGFR-1 function may therefore be used to counteract chemotherapy-induced retention of tumor cells within the metastatic niche, providing a novel level of tumor control in chemotherapy. PMID- 21975930 TI - Decreased lymphangiogenesis and lymph node metastasis by mTOR inhibition in head and neck cancer. AB - Despite our improved understanding of cancer, the 5-year survival rate for head and neck squamous cell carcinomas (HNSCC) patients remains relatively unchanged at 50% for the past three decades. HNSCCs often metastasize to locoregional lymph nodes, and lymph node involvement represents one of the most important prognostic factors of poor clinical outcome. Among the multiple dysregulated molecular mechanism in HNSCCs, emerging basic, preclinical, and clinical findings support the importance of the mTOR signaling route in HNSCC progression. Indeed, we observed here that the activation of mTOR is a widespread event in clinical specimens of HNSCCs invading locoregional lymph nodes. We developed an orthotopic model of HNSCC consisting of the implantation of HNSCC cells into the tongues of immunocompromised mice. These orthotopic tumors spontaneously metastasize to the cervical lymph nodes, where the presence of HNSCC cells can be revealed by histologic and immunohistochemical evaluation. Both primary and metastatic experimental HNSCC lesions exhibited elevated mTOR activity. The ability to monitor and quantitate lymph node invasion in this model system enabled us to explore whether the blockade of mTOR could impact HNSCC metastasis. We found that inhibition of mTOR with rapamycin and the rapalog RAD001 diminished lymphangiogenesis in the primary tumors and prevented the dissemination of HNSCC cancer cells to the cervical lymph nodes, thereby prolonging animal survival. These findings may provide a rationale for the future clinical evaluation of mTOR inhibitors, including rapamycin and its analogues, as part of a molecular targeted metastasis preventive strategy for the treatment of patients with HNSCC. PMID- 21975932 TI - EGFR-AKT-Smad signaling promotes formation of glioma stem-like cells and tumor angiogenesis by ID3-driven cytokine induction. AB - Aberrant activation of receptor tyrosine kinases (RTK) is causally linked to the pathobiological traits of glioblastoma and genesis of glioma stem-like cells (GSC), but the underlying mechanism is still unknown. Here, we show that epidermal growth factor receptor (EGFR) signaling regulates the proliferation, angiogenesis, and acquisition of GSC characteristics by inducing inhibitor of differentiation 3 (ID3) and ID3-regulated cytokines [GRO1 and interleukins (IL)-6 and 8] induction. We found that EGFR-mediated ID3 expression was regulated by Smad5, which was directly phosphorylated by AKT. Furthermore, ID3 alone imparted GSC features to primary astrocytes derived from Ink4a/Arf-deficient mouse, and EGFR-ID3-IL-6 signaling axis gave rise to tumor cell heterogeneity. Conversely, EGFR inhibitors suppressed EGFR-AKT-Smad5-driven induction of ID3, which led to a decrease in the tumorsphere forming ability of GSCs and U87MG cells that possess an active mutant EGFR, EGFRvIII, without obvious cytotoxic effects. However, these cells seemed to regain colonogenic ability after removal of the EGFR inhibitors. Together, the results delineate a novel integrative molecular mechanism in which the RTK-ID signaling pathway governs genesis and maintenance of GBM histopathologic features, such as GSCs-based tumor initiation, progression, and angiogenesis. PMID- 21975931 TI - Increased skin papilloma formation in mice lacking glutathione transferase GSTP. AB - The glutathione S-transferase GSTP is overexpressed in many human cancers and chemotherapy-resistant cancer cells, where there is evidence that GSTP may have additional functions beyond its known catalytic role. On the basis of evidence that Gstp-deficient mice have a comparatively higher susceptibility to skin carcinogenesis, we investigated whether this phenotype reflected an alteration in carcinogen detoxification or not. For this study, Gstp(-/-) mice were interbred with Tg.AC mice that harbor initiating H-ras mutations in the skin. Gstp(-/ )/Tg.AC mice exposed to the proinflammatory phorbol ester 12-O tetradecanoylphorbol-13-acetate (TPA) exhibited higher tumor incidence and multiplicity with a significant thickening of skin after treatment, illustrating hyperproliferative growth. Unexpectedly, we observed no difference in cellular proliferation or apoptosis or in markers of oxidative stress, although higher levels of the inflammatory marker nitrotyrosine were found in Gstp(-/-)/Tg.AC mice. Instead, gene set enrichment analysis of microarray expression data obtained from skin revealed a more proapoptotic and proinflammatory environment shortly after TPA treatment. Within 4 weeks of TPA treatment, Gstp(-/-)/Tg.AC mice displayed altered lipid/sterol metabolism and Wnt signaling along with aberrant processes of cytoskeletal control and epidermal morphogenesis at both early and late times. In extending the evidence that GSTP has a vital role in normal homeostatic control and cancer prevention, they also strongly encourage the emerging concept that GSTP is a major determinant of the proinflammatory character of the tumor microenvironment. This study shows that the GSTP plays a major role in carcinogenesis distinct from its role in detoxification and provides evidence that the enzyme is a key determinant of the proinflammatory tumor environment. PMID- 21975933 TI - Novel histone demethylase LSD1 inhibitors selectively target cancer cells with pluripotent stem cell properties. AB - Histone modification determines epigenetic patterns of gene expression with methylation of histone H3 at lysine 4 (H3K4) often associated with active promoters. LSD1/KDM1 is a histone demethylase that suppresses gene expression by converting dimethylated H3K4 to mono- and unmethylated H3K4. LSD1 is essential for metazoan development, but its pathophysiologic functions in cancer remain mainly uncharacterized. In this study, we developed specific bioactive small inhibitors of LSD1 that enhance H3K4 methylation and derepress epigenetically suppressed genes in vivo. Strikingly, these compounds inhibited the proliferation of pluripotent cancer cells including teratocarcinoma, embryonic carcinoma, and seminoma or embryonic stem cells that express the stem cell markers Oct4 and Sox2 while displaying minimum growth-inhibitory effects on non-pluripotent cancer or normal somatic cells. RNA interference-mediated knockdown of LSD1 expression phenocopied these effects, confirming the specificity of small molecules and further establishing the high degree of sensitivity and selectivity of pluripotent cancer cells to LSD1 ablation. In support of these results, we found that LSD1 protein level is highly elevated in pluripotent cancer cells and in human testicular seminoma tissues that express Oct4. Using these novel chemical inhibitors as probes, our findings establish LSD1 and histone H3K4 methylation as essential cancer-selective epigenetic targets in cancer cells that have pluripotent stem cell properties. PMID- 21975935 TI - Sonic hedgehog pathway promotes metastasis and lymphangiogenesis via activation of Akt, EMT, and MMP-9 pathway in gastric cancer. AB - Activation of sonic hedgehog (Shh) signaling has been implicated in progression of a variety of tumors. In this study, we elucidated a role for Shh in the invasion of gastric tumors and determined the mechanism by which Shh is regulated. Immunohistochemical analysis of 178 primary human gastric tumor biopsies indicated that Shh expression was positively correlated with lymph node metastasis, high lymphatic vessel density, and poor prognosis. In mouse xenograft models of human gastric cancer, enforced expression of Shh significantly enhanced the incidence of lung metastasis compared with nonexpressing controls. Mechanistic investigations revealed that phosphoinositide 3-kinase (PI3K)/Akt inhibition blocked Shh-induced epithelial-mesenchyme transition, the activity of matrix metalloproteinase 9 (MMP-9), and lymphangiogenesis, reducing tumor invasiveness and metastasis. Taken together, our findings establish that Shh signaling promotes the metastasis of gastric cancer through activation of the PI3K/Akt pathway, which leads to mesenchymal transition and MMP-9 activation. These findings offer preclinical validation of Shh as a candidate therapeutic target for treatment of metastatic gastric cancers. PMID- 21975934 TI - c-MYC functions as a molecular switch to alter the response of human mammary epithelial cells to oncostatin M. AB - Cytokines play an important role in creating an inflammatory microenvironment, which is now considered a hallmark of cancer. Although tumor cells can exploit cytokine signaling to promote growth, invasion, and metastasis, the response of normal and premalignant epithelial cells to cytokines present in a developing tumor microenvironment remains unclear. Oncostatin M (OSM), an IL-6 family cytokine responsible for STAT3 activation, has been implicated in cancer development, progression, invasion, and metastasis. Paradoxically, OSM can also suppress the growth of normal cells and certain tumor-derived cell lines. Using isogenic human mammary epithelial cells (HMEC) at different stages of neoplastic transformation, we found that OSM signaling suppressed c-MYC expression and engaged a p16- and p53-independent growth arrest that required STAT3 activity. Inhibition of STAT3 activation by expressing a dominant-negative STAT3 protein or a STAT3-shRNA prevented the OSM-mediated arrest. In addition, expression of c-MYC from a constitutive promoter also abrogated the STAT3-mediated arrest, and strikingly, cooperated with OSM to promote anchorage-independent growth (AIG), a property associated with malignant transformation. Cooperative transformation by c-MYC and OSM required PI3K and AKT signaling, showing the importance of multiple signaling pathways downstream of the OSM receptor in defining the cellular response to cytokines. These findings identify c-MYC as an important molecular switch that alters the cellular response to OSM-mediated signaling from tumor suppressive to tumor promoting. PMID- 21975937 TI - Electron spin labeling reveals the highly dynamic N-terminal arms of the SOS mutagenesis protein UmuD. AB - Electron paramagnetic resonance (EPR) spectroscopy was used to probe the conformational dynamics of the N-terminal arms of the umuD gene products. We determined that the arms of UmuD(2) display a large degree of motion, are largely unbound from the globular C-terminal domain, and that the free energy of dissociation is +2.1 kJ mol(-1). PMID- 21975936 TI - Secretory IgA's complex roles in immunity and mucosal homeostasis in the gut. AB - Secretory IgA (SIgA) serves as the first line of defense in protecting the intestinal epithelium from enteric toxins and pathogenic microorganisms. Through a process known as immune exclusion, SIgA promotes the clearance of antigens and pathogenic microorganisms from the intestinal lumen by blocking their access to epithelial receptors, entrapping them in mucus, and facilitating their removal by peristaltic and mucociliary activities. In addition, SIgA functions in mucosal immunity and intestinal homeostasis through mechanisms that have only recently been revealed. In just the past several years, SIgA has been identified as having the capacity to directly quench bacterial virulence factors, influence composition of the intestinal microbiota by Fab-dependent and Fab-independent mechanisms, promote retro-transport of antigens across the intestinal epithelium to dendritic cell subsets in gut-associated lymphoid tissue, and, finally, to downregulate proinflammatory responses normally associated with the uptake of highly pathogenic bacteria and potentially allergenic antigens. This review summarizes the intrinsic biological activities now associated with SIgA and their relationships with immunity and intestinal homeostasis. PMID- 21975938 TI - Strategies for pathway analysis from GWAS data. AB - Genome-wide association studies (GWAS) are a standard approach for investigating the relationship of common variation within the human genome to a given phenotype of interest. However, single-allele association results published for many GWAS studies represent only the tip of the iceberg for the information that can be extracted from these datasets. The primary analysis strategy for GWAS entails association analysis in which only the single nucleotide polymorphisms (SNPs) with the strongest p values are declared statistically significant due to issues arising from multiple testing and type I error concerns. Factors such as locus heterogeneity, epistasis, and multiple genes conferring small effects contribute to the complexity of the genetic models underlying phenotype expression. Thus, many biologically meaningful associations having lower effect sizes at individual genes are overlooked, as they are difficult to separate from a sea of false positive associations. Organizing these individual SNPs into biologically meaningful groups to look at overall effects of minor perturbations to genes and pathways is desirable. This pathway-based approach provides researchers with insight into the functional foundations of the phenotype being studied and allows testing of various genetic scenarios. PMID- 21975939 TI - Using the PhenX Toolkit to Add Standard Measures to a Study. AB - The PhenX (consensus measures for Phenotypes and eXposures) Toolkit (https://www.phenxtoolkit.org/) offers high-quality, well-established measures of phenotypes and exposures for use by the scientific community. The Toolkit contains 295 measures drawn from 21 research domains (fields of research). The measures were selected by Working Groups of domain experts using a consensus process that included input from the scientific community. The Toolkit provides a description of each PhenX measure, the rationale for including it in the Toolkit, protocol(s) for collecting the measure, and supporting documentation. Users can browse by measures, domains, or collections, or can search the Toolkit using the Smart Query Tool. Once users have selected some measures, they can download a customized Data Collection Worksheet that specifies what information needs to be collected, and a Data Dictionary that describes each variable included in their Data Collection Worksheet. To help researchers find studies with comparable data, PhenX measures and variables are being mapped to studies in the database of Genotypes and Phenotypes (dbGaP). PMID- 21975940 TI - The UCSC Genome Browser. AB - The University of California Santa Cruz (UCSC) Genome Browser is a popular Web based tool for quickly displaying a requested portion of a genome at any scale, accompanied by a series of aligned annotation "tracks." The annotations generated by the UCSC Genome Bioinformatics Group and external collaborators include gene predictions, mRNA and expressed sequence tag alignments, simple nucleotide polymorphisms, expression and regulatory data, phenotype and variation data, and pairwise and multiple-species comparative genomics data. All information relevant to a region is presented in one window, facilitating biological analysis and interpretation. The database tables underlying the Genome Browser tracks can be viewed, downloaded, and manipulated using another Web-based application, the UCSC Table Browser. Users can upload personal datasets in a wide variety of formats as custom annotation tracks in both browsers for research or educational purposes. This unit describes how to use the Genome Browser and Table Browser for genome analysis, download the underlying database tables, and create and display custom annotation tracks. PMID- 21975942 TI - Searching NCBI Databases Using Entrez. AB - One of the most widely used interfaces for the retrieval of information from biological databases is the NCBI Entrez system. Entrez capitalizes on the fact that there are pre-existing, logical relationships between the individual entries found in numerous public databases. The existence of such natural connections, mostly biological in nature, argued for the development of a method through which all the information about a particular biological entity could be found without having to sequentially visit and query disparate databases. Two basic protocols describe simple, text-based searches, illustrating the types of information that can be retrieved through the Entrez system. An alternate protocol builds upon the first basic protocol, using additional, built-in features of the Entrez system, and providing alternative ways to issue the initial query. The support protocol reviews how to save frequently issued queries. Finally, Cn3D, a structure visualization tool, is also discussed. PMID- 21975941 TI - Next generation sequencing to characterize mitochondrial genomic DNA heteroplasmy. AB - This protocol describes the methodology to characterize mitochondrial DNA (mtDNA) heteroplasmy by parallel sequencing. Mitochondria play an important role in essential cellular functions. Each eukaryotic cell contains hundreds of mitochondria with hundreds of mitochondria genomes. Mutant and wild-type mtDNA may co-exist as heteroplasmy, and cause human disease. The purpose of this protocol is to simultaneously determine mtDNA sequence and quantify the heteroplasmic level. This protocol includes a two-fragment mitochondrial genome DNA PCR amplification. The PCR product is then mixed at an equimolar ratio. The samples are then barcoded and sequenced with high-throughput, next-generation sequencing technology. This technology is highly sensitive, specific, and accurate in determining mtDNA mutations and the level of heteroplasmy. PMID- 21975943 TI - Inhibition by zinc of deoxycholate-induced apoptosis in HCT-116 cells. AB - The bile acid, deoxycholate, can induce apoptosis although the effect of trace elements on such cell death is unknown. The aim of this study was to determine if deoxycholate-induced apoptosis is influenced by zinc. HCT-116 colon epithelial cells were pre-treated with zinc and then exposed to deoxycholate. Membrane blebbing, formation of apoptotic bodies, and greater overall production of reactive oxygen species (ROS) occurred in cells exposed to deoxycholate, but zinc inhibited the occurrence of these three events caused by deoxycholate. Upon finer analysis, stimulation of mitochondrial superoxide production, mitochondrial dysfunction, and cytochrome c release were detected in cells exposed to deoxycholate, but zinc did not inhibit any of these three effects caused by deoxycholate. Additionally, caspase-3 activation, plasma membrane phospholipid translocation, and also chromatin condensation and fragmentation were observed in cells exposed to deoxycholate, but all of these effects of deoxycholate, including the greater overall ROS production, were all inhibited by zinc. Because zinc did not prevent the three mitochondrial effects caused by deoxycholate, the last set of findings suggested that zinc hampered activation of an initiator caspase upstream of effector caspase-3, in inhibiting deoxycholate-induced HCT 116 cell death. In examining this possibility, it was found that caspase-8 activation caused by deoxycholate was blocked by zinc. Collectively, the results suggest that zinc can inhibit deoxycholate-induced apoptotic cell death mediated by caspases. PMID- 21975944 TI - Conformational polymorphism on imatinib mesylate: grinding effects. AB - Crystal structures of polymorphs alpha and beta of imatinib mesylate were obtained. Thermal behavior and grinding effects were studied by X-ray powder diffraction and differential scanning calorimetry techniques. Molecules in forms alpha and beta exhibit significant conformational differences due to dissimilar intramolecular interactions, which stabilize their molecular conformations. In spite of that, both crystal structures present a dimer-chain arrangement. Dimers are mainly determined by hydrogen bonding interactions and some weak pi-pi interactions. Connections between dimers are provided by mesylate ions to determine chains of dimers. Neighboring chains are linked by very weak interactions: C-H...pi interactions in form alpha and pi-pi interactions in form beta. At room temperature, thermal disorder was observed in the mesylate ion in form alpha, which could be removed at low temperatures (-123 degrees C). Form beta was found to be the more stable form at room temperature. Both polymorphs exhibit a tendency to generate amorphous material by grinding, which can be converted to a crystalline phase by either temperature or aging. When amorphous crystallization is kinetically studied at room temperature, form beta is obtained after a week. Conversely, when the crystallization is activated by temperature, the final obtained crystal form depends on the starting material, proving the importance of seeding. PMID- 21975945 TI - Multiple hydrogen bondings in a platinum complex. AB - An unprecedented example of a platinum(II) complex with simultaneous formation of intermolecular NH...I-Pt and CH...I-Pt H-bondings (with neighboring platinum center) and an intramolecular CH...Pt hydrogen bonding in solid state is described. There are indications showing that the complex in solution probably forms a different kind of H-bonding type interaction. PMID- 21975946 TI - Variability of medial and posterior offset in patients with fourth-generation stemmed shoulder arthroplasty. AB - PURPOSE: Most anthropometric data on the proximal humerus has been obtained from deceased healthy individuals with no deformities. Endoprostheses are implanted for primary and secondary osteoarthritis, rheumatoid arthritis,humeral-head necrosis, fracture sequelae and other humeral-head deformities. This indicates that pathologicoanatomical variability may be greater than previously assumed. We therefore investigated a group of patients with typical shoulder replacement diagnoses, including posttraumatic and rheumatic deformities. MATERIAL AND METHODS: One hundred and twenty-two patients with a double eccentrically adjustable shaft endoprosthesis served as a specific dimension gauge to determine in vivo the individual humeral-head rotation centres from the position of the adjustable prosthesis taper and the eccentric head. RESULTS: All prosthesis heads were positioned eccentrically.The entire adjustment range of the prosthesis of 12 mm medial/lateral and 6 mm dorsal/ventral was required. Mean values for effective offset were 5.84 mm mediolaterally[standard deviation (SD) 1.95, minimum +2, maximum +11]and 1.71 mm anteroposteriorly (SD 1.71, minimum -3,maximum 3 mm), averaging 5.16 mm (SD 1.76, minimum +2,maximum + 10). The posterior offset averaged 1.85 mm(SD 1.85, minimum -1, maximum + 6 mm). CONCLUSIONS: In summary, variability of the combined medial and dorsal offset of the humeral-head rotational centre determined in patients with typical underlying diagnoses in shoulder replacement was not greater than that recorded in the literature for healthy deceased patients.The range of deviation is substantial and shows the need for an adjustable prosthetic system. PMID- 21975947 TI - Iron oxide magnetic nanoparticles used as probing agents to study the nanostructure of mixed self-assembled monolayers. AB - Self-assembled monolayers (SAMs) of organic molecules are of exceptional technological importance since they represent a convenient, flexible, and simple system for tuning the chemical and physical properties of surfaces. The fine control of surface properties is directly dependent on the structure of mixed SAMs which is difficult to characterize at the nanoscale with usual techniques such as scanning probe microscopies. In this study, we report on a general method to investigate at the nanoscale the structure of molecular patterns which consist in SAMs of two components. Iron oxide nanoparticles (NPs) have been used as probing agents to study indirectly the structure of mixed SAMs. Mixed SAMs were prepared by the replacement of mercaptododecane (MDD) adsorbed by mercaptoundecanoic acid (MUA) molecules on gold substrates. Therefore, the SAM surface displays both chelating carboxylic terminal groups and non-chelating methylene terminal groups. As NPs have been previously demonstrated to specifically interact with carboxylic acid groups, the increasing density in NPs was correlated with the evolution of the COOH/CH(3) terminal groups ratio. Therefore the structure of mixed SAMs was studied indirectly as well as the kinetic of the replacement reaction and its mechanism. With this aim, we took advantage of the SPR properties of the gold substrate and of the high refractive index of iron oxide nanoparticles to follow their assembling on mixed SAMs as a time resolved study. The high sensitivity and tuning of the SPR signal over a wide range of wavelengths are correlated with the NP density. Furthermore, SEM combined with image analysis has allowed studying the replacement rate of MDD by MUA in SAMs. We took also advantages of the magnetic properties of NPs to evaluate qualitatively the replacement of thiol molecules. PMID- 21975948 TI - Enhancing masculinity by slandering homosexuals: the role of homophobic epithets in heterosexual gender identity. AB - The current studies investigate the effects of homophobic labels on the self perception of heterosexual males, hypothesizing that when exposed to homophobic epithets, they are motivated to underline their masculinity and claim a distinctly heterosexual identity by taking distance from homosexuals and, to a lesser degree, from women. Heterosexual male participants were subliminally (Study 1) and supraliminally (Study 2) primed either by a homophobic epithet or by a category label, and completed the Traditional Beliefs About Gender and Gender Identity scale. Participants stressed their heterosexual identity, but not their gender distinctiveness, when exposed to homophobic epithets, compared to category labels. Study 2 demonstrated that the relation between the homophobic label and the participants' heterosexual identity was mediated by how negatively they reacted to the antigay label. Heterosexual identity was enhanced in reaction to homophobic labels but not to an equally derogatory label referring to regional identity. Results are discussed within an intergroup framework. PMID- 21975949 TI - Reappraising the situation and its impact on aggressive behavior. AB - Much work has focused on how reappraisal is related to emotions, but not behaviors. Two experiments advanced aggression theory by (a) testing how cognitive and attributional forms of reappraisal are related to aggressive affect and behavior, (b) testing variables that theoretically mediate the relation between attributional reappraisal and aggressive behavior, (c) testing the moderating influences of cognitive and attributional reappraisal on aggressive behavior, and (d) developing and testing an intervention aimed at reducing vengeance through reappraisal training. Study 1 used an essay writing task in a 3 (feedback: provocation, no feedback, praise) * 2 (mitigating information: present, absent) experimental design. Provoked participants who did not receive mitigating information were significantly more aggressive than provoked participants who received mitigating information. State vengeance was a significant mediator. Study 2 examined an experimental intervention on vengeance over a 16-week semester. Intervention participants who had the largest increase in reappraisal displayed the greatest decrease in vengeance. Overall, these findings suggest that reappraisal reduces vengeance and aggressive behavior. PMID- 21975950 TI - Temperature-dependent conductivity of Emim+ (Emim+ = 1-ethyl-3-methyl imidazolium) confined in channels of a metal-organic framework. AB - A 3D metal-organic framework, featuring three kinds of cation channels, was obtained through an ionothermal reaction. Investigation on its temperature dependent conductivity indicates the contribution of order and disorder of the Emim(+) (Emim(+) = 1-ethyl-3-methyl imidazolium bromide) in the channel to its conductivity. PMID- 21975951 TI - Protolimonoids and norlimonoids from the stem bark of Toona ciliata var. pubescens. AB - Six new tirucallane protolimonoids, toonapubesins A-F (1-6), one new rearranged tirucallane protolimonoid, toonapubesin G (7), and two new 21,22,23 trinorapotirucallane limonoids, toonapubesic acids A (8) and B (9), possessing an unprecedented carbon skeleton, along with five known tirucallane protolimonoids (10-14) and one known apotirucallane limonoid (15), were isolated from the stem bark of Toona ciliata var. pubescens. Their structures and relative configurations were determined by detailed spectroscopic analysis and by chemical methods. The proposed structures of 8 and 11 were confirmed by X-ray diffraction analysis of their respective derivatives (8a and 11a). The absolute configuration of 8 was determined by a novel solid-state TDDFT ECD approach on its derivative 8a while the absolute configuration of 10 was determined by the modified Mosher's method. In addition, the structures of dyvariabilin H (10c) proposed by Sticher et al. and cneorin-NP(36) (11b) by Mondon et al. were corrected as 10 and 11, respectively. Toonapubesin G (7) showed promising inhibitory activity against CDC25B with an IC(50) value of 2.1 MUM, while compound 8a showed significant cell protecting activity against H(2)O(2)-induced SH-SY5Y cell damage with 11.5% increase in cell viability. PMID- 21975952 TI - 23-Gauge transconjunctival sutureless vitrectomy for retained lens fragments after complicated cataract surgery. AB - PURPOSE: The purpose of this study was to evaluate the effectiveness and safety of 23-gauge (23-G) transconjunctival sutureless vitrectomy in patients with retained lens fragments after complicated cataract surgery. METHODS: In this retrospective consecutive case series, 17 eyes of 17 patients with retained lens fragments after complicated cataract surgery and managed by using 23-G transconjunctival sutureless vitrectomy were evaluated between January 2007 and March 2009 at our institution. RESULTS: Mean follow-up time was 8.5 +/- 3.00 months. Nine patients (53%) were pseudophakic, and 8 (47%) were aphakic. A foldable acrylic intraocular lens was implanted in eight eyes with aphakia. In 2 eyes (11.8%), one of 23-G sclerotomy port was enlarged and intravitreal phacoemulsification was performed with 20-gauge phacofragmatome to remove hard nucleus. Visual acuity improved in 100% of eyes and was 20/40 or better in 70.6% of eyes. Postoperative complications were transient elevation of intraocular pressure (29.4%), decentralization of the intraocular lens (5.9%), fibrin reaction (5.9%), mild vitreous hemorrhage (5.9%), and macular retinal pigment epithelial changes (5.9%). CONCLUSION: Twenty-three-gauge transconjunctival sutureless vitrectomy was observed to be effective and safe in patients with retained lens fragments after complicated cataract surgery. In cases with hard nucleus, 23-G vitrectomy probe may not be adequate to remove the lens fragments. PMID- 21975953 TI - Protein glycosylation and its impact on biotechnology. AB - Glycosylation is a post-translational modification that is of paramount importance in the production of recombinant pharmaceuticals as most recombinantly produced therapeutics are N- and/or O-glycosylated. Being a cell-system-dependent process, it also varies with expression systems and growth conditions, which result in glycan microheterogeneity and macroheterogeneity. Glycans have an effect on drug stability, serum half-life, and immunogenicity; it is therefore important to analyze and optimize the glycan decoration of pharmaceuticals. This review summarizes the aspects of protein glycosylation that are of interest to biotechnologists, namely, biosynthesis and biological relevance, as well as the tools to optimize and to analyze protein glycosylation. PMID- 21975955 TI - Microenvironment design for stem cell fate determination. AB - Stem cells are characterized by their dual ability for self-renewal and differentiation, potentially yielding large numbers of cells that can be used in cell therapy and tissue engineering for repairing devastating diseases. Attaining control over stem cell fate decision in culture is a great challenge since these cells integrate a complex array of "niche" signals, which regulate their fate. Given this, the recent findings that synthetic microenvironments can be designed to gain some level of control over stem cell fate are encouraging. This chapter provides an overview of the current state and knowledge of the design of synthetic microenvironments bio-inspired by the adult stem cell niche. We describe the biomaterials used for reconstituting the niche, highlighting the bioengineering principles used in the process. Such synthetic microenvironments constitute powerful tools for elucidating stem cell regulatory mechanisms that should fuel the development of advanced culture systems with accurate regulation of stem cell fate. PMID- 21975956 TI - Bioresorption and degradation of biomaterials. AB - The human body is a composite structure, completely constructed of biodegradable materials. This allows the cells of the body to remove and replace old or defective tissue with new material. Consequently, artificial resorbable biomaterials have been developed for application in regenerative medicine. We discuss here advantages and disadvantages of these bioresorbable materials for medical applications and give an overview of typically used metals, ceramics and polymers. Methods for the quantification of bioresorption in vitro and in vivo are described. The next challenge will be to better understand the interface between cell and material and to use this knowledge for the design of "intelligent" materials that can instruct the cells to build specific tissue geometries and degrade in the process. PMID- 21975957 TI - Self-assembled dye-layered double hydroxide-Pt nanoparticles: a novel H2 evolution system with remarkably enhanced stability. AB - A novel photocatalytic hydrogen evolution system was constructed by using well dispersed layered double hydroxide (LDH) to immobilize the photosensitizer (rose bengal, RB) and photocatalyst (Pt). The produced amount of H(2) from such a self assembled RB-LDH-Pt system is a few times more than that from the Free system (without LDH). Moreover, RB-LDH-Pt can be reused for at least 6 times (still having 64% of the activity in the 6(th) run) by a simple method of centrifugation which makes this system more economical by recycling the expensive Pt. The total turnover number (TON) obtained after six runs for RB-LDH-Pt was calculated to be 304 based on Pt, which gave at least 13-fold enhancement compared with that from the Free system. PMID- 21975958 TI - [Report of a case of poisoning by double snake bite with neurotrope venom at the National Donka Hospital, Conakry (Guinea)]. AB - Poisoning by snake bites remains an important cause of death in developing countries and in Africa in particular. Positive diagnosis is mostly easy because of the interrogation of the family and the local reactions that occur in the bite area. However, it is easy to know the type of the snake because the description by the victim is often unclear. We report a case of poisoning due to double bite by an unidentified snake that led to a clinical picture dominated by neurological and respiratory signs, suggestive of a neurotoxin poisoning in a young man living in rural area. Despite the delay in the management due to the ritual traditional treatment, the symptoms improved after the administration of polyvalent anti venom. This observation raises the delicate problem of identification of snakes from the clinical symptomatology observed, considering their variety PMID- 21975954 TI - Harnessing cell-biomaterial interactions for osteochondral tissue regeneration. AB - Articular cartilage that is damaged or diseased often requires surgical intervention to repair the tissue; therefore, tissue engineering strategies have been developed to aid in cartilage regeneration. Tissue engineering approaches often require the integration of cells, biomaterials, and growth factors to direct and support tissue formation. A variety of cell types have been isolated from adipose, bone marrow, muscle, and skin tissue to promote cartilage regeneration. The interaction of cells with each other and with their surrounding environment has been shown to play a key role in cartilage engineering. In tissue engineering approaches, biomaterials are commonly used to provide an initial framework for cell recruitment and proliferation and tissue formation. Modifications of the properties of biomaterials, such as creating sites for cell binding, altering their physicochemical characteristics, and regulating the delivery of growth factors, can have a significant influence on chondrogenesis. Overall, the goal is to completely restore healthy cartilage within an articular cartilage defect. This chapter aims to provide information about the importance of cell-biomaterial interactions for the chondrogenic differentiation of various cell populations that can eventually produce functional cartilage matrix that is indicative of healthy cartilage tissue. PMID- 21975959 TI - To transplant or not to transplant: certainly one of the questions. PMID- 21975961 TI - Hypothyroidism is a rare cause of isolated constipation. AB - The prevalence of constipation in children is high and accounts for a large percentage of pediatric and pediatric gastroenterology visits. Thyroid testing is frequently ordered to evaluate constipation and other gastrointestinal complaints in children. We reviewed all of the patients with thyroid testing ordered by our pediatric gastroenterology division during a 5-year period. We found 873 patients on whom thyroid testing was performed, and 56 patients had evidence of hypothyroidism. Nine patients had constipation and clinically significant hypothyroidism in this group; however, only 1 child had constipation as their sole presenting symptom. The contribution of occult hypothyroidism to isolated constipation in children may have been previously overestimated. PMID- 21975962 TI - Glycogenic hepatopathy. PMID- 21975963 TI - A decade of hospital discharges related to eosinophilic esophagitis. AB - Eosinophilic esophagitis (EoE) is a recently characterized chronic, allergic, gastrointestinal disorder. Using the Pediatric Health Information System, we report trends in diagnostic codes related to EoE in inpatients from 1999 through 2010. Esophagitis not elsewhere classifiable, EoE, and dysphagia have increased over time. Similar to other allergic disorders, EoE appears to be increasing across the United States. PMID- 21975964 TI - Autoimmune cholecystitis. PMID- 21975965 TI - Safe and effective procedural sedation for gastrointestinal endoscopy in children. AB - OBJECTIVE: The aim of the study was to assess, by a review of published evidence, the safest and most effective way to provide procedural sedation (PS) in children undergoing gastrointestinal endoscopy (GIE). METHODS: The databases MEDLINE, Cochrane Library, and Embase were used. Search terms "endoscopy, gastrointestinal" or "endoscopy, digestive system" were combined with "sedation," "conscious sedation," "moderate sedation," "deep sedation," and "hypnotics and sedatives." The final review was restricted to studies reporting specifically on safety (incidences of adverse events) and/or effectiveness (time characteristics, need for supplemental sedation, need for restraint, procedural success, provider satisfaction, and patient comfort) of PS for GIE in children younger than 18 years. RESULTS: The search yielded 182 references and the final selection included 11 randomized controlled trials (RCTs) and 15 non-RCTs. Six sedation categories were identified: propofol, opioid/benzodiazepine, premedication, ketamine-, sevoflurane-, and midazolam-based. Only a few RCTs have compared different categories. Opioid/benzodiazepine- and propofol-based PS have a similar safety profile and a low incidence of major adverse events. Propofol-based sedation turned out to be the most effective regimen, with effectiveness comparable to general anesthesia. The addition of midazolam, fentanyl, remifentanil, and/or ketamine to propofol may increase the effectiveness without creating more adverse events. Data on midazolam-, ketamine- and sevoflurane-based sedation were generally too limited to draw conclusions. CONCLUSIONS: Despite a lack of RCTs containing all aspects of effectiveness and safety, the present evidence indicates propofol-based PS to be the best practice for PS in children undergoing GIE. Propofol can be safely administered by specifically trained nonanesthesiologists. PMID- 21975966 TI - Bioconversion into ethanol of decorticated red sorghum (Sorghum bicolor L. Moench) supplemented with its phenolic extract or spent bran. AB - The effect of extracted phenolics or spent bran added to decorticated red sorghum kernels during fuel ethanol production was studied and compared to maize and whole red and white sorghums. After liquefaction, free amino nitrogen ranged from 65 to 101 mg/l and at the end of saccharification all mashes had approx. 80 g glucose and 2-5 g maltose/100 g meal (dry basis). Saccharified worts were fermented giving 50-90 ml ethanol/l. The lowest fermentation efficiency (76%) was obtained in the white sorghum. Ethanol yields indicate that sorghum bran or its associated phenolics did not significantly affect the efficiency of the sequential steps involved in ethanol production. Red sorghum is a good alternative to maize to produce ethanol and the difference regarding white sorghum and maize was mainly due to endosperm protein structure and composition. PMID- 21975967 TI - Genetic determinants of variability in glycated hemoglobin (HbA(1c)) in humans: review of recent progress and prospects for use in diabetes care. AB - Glycated hemoglobin A(1c) (HbA(1c)) indicates the percentage of total hemoglobin that is bound by glucose, produced from the nonenzymatic chemical modification by glucose of hemoglobin molecules carried in erythrocytes. HbA(1c) represents a surrogate marker of average blood glucose concentration over the previous 8 to 12 weeks, or the average lifespan of the erythrocyte, and thus represents a more stable indicator of glycemic status compared with fasting glucose. HbA(1c) levels are genetically determined, with heritability of 47% to 59%. Over the past few years, inroads into understanding genetic predisposition by glycemic and nonglycemic factors have been achieved through genomewide analyses. Here I review current research aimed at discovering genetic determinants of HbA(1c) levels, discussing insights into biologic factors influencing variability in the general and diabetic population, and across different ethnicities. Furthermore, I discuss briefly the relevance of findings for diabetes monitoring and diagnosis. PMID- 21975968 TI - Characterization of the nucleophilic reactivities of thiocarboxylate, dithiocarbonate and dithiocarbamate anions. AB - The kinetics of the reactions of thiocarboxylate and thiocarbonate anions with benzhydrylium ions have been determined in acetonitrile solution using laser flash photolytic techniques. The second-order rate constants (k) correlate linearly with the electrophilicity parameters E of the benzhydrylium ions, as required by the correlation log k (20 degrees C) = s(N)(N + E) (J. Am. Chem. Soc., 2001, 123, 9500-9512), allowing us to calculate the nucleophile-specific parameters N and s(N) for these anions. With these parameters, a direct comparison of the reactivities of thiocarboxylate, dithiocarbonate and dithiocarbamate anions with other nucleophiles becomes possible. PMID- 21975969 TI - Flowering timing prediction in Australian native understorey species (Acrotriche R.Br Ericaceae) using meteorological data. AB - The aim of this study was to determine the climatic influences on floral development for five members of the Australian native plant genus Acrotriche R.Br (Ericaceae). An observed period of summer floral dormancy suggests temperature is involved in flowering regulation in these species. Models were developed to determine temperature requirements associated with the likelihood of flowering occurring on any one day. To this end, the timing of flowering and meteorological data were collated for several sites, and multivariate logistic regressions performed to identify variables with a significant influence on flowering timing. The resultant models described a large amount of variation in flowering presence/absence, with (r2) values ranging from 0.72 to 0.79. Temperature was identified as influential on both floral development and flowering timing in each of the study species. The positive influence of short photoperiods on flowering in three of the winter flowering species was not surprising. However, the reporting here ofa significant association between interdiurnal temperature and flowering in one species is novel. The predictive power of the models was validated through a jackknife sequential recalculation approach, revealing strong positive and negative predictive ability for flowering for four of the five species. Applications of the models include assisting in determination of the suitability of areas for vegetation restoration and identifying the possible effects of climate change on flowering in the study species. PMID- 21975971 TI - Resident burnout: working hours or working conditions? PMID- 21975972 TI - The revolution in medical education-the role of simulation. AB - The last major change in medical education was the Flexner Report, over a century ago. Since that time, iterative improvements have occurred to the question-and answer and "see one, do one, teach one" educational environment. However, multiple external forces-from the 80-hour work week to the emphasis on patient safety to competing demands on student and faculty time-have raised calls for a fundamental revamping of the entire medical educational process. Fortunately, new methods, curricula, and processes, such as Accreditation Council for Graduate Medical Education competencies or Objective Structured Assessment of Technical Skills, as well as innovative technologies such as web-based learning and simulation, have provided opportunities to support the revolution in medical education that will be responsive to national priorities, the public concern, and, most of all, to patient safety. PMID- 21975970 TI - Daily average temperature and mortality among the elderly: a meta-analysis and systematic review of epidemiological evidence. AB - The impact of climate change on the health of vulnerable groups such as the elderly has been of increasing concern. However, to date there has been no meta analysis of current literature relating to the effects of temperature fluctuations upon mortality amongst the elderly. We synthesised risk estimates of the overall impact of daily mean temperature on elderly mortality across different continents. A comprehensive literature search was conducted using MEDLINE and PubMed to identify papers published up to December 2010. Selection criteria including suitable temperature indicators, endpoints, study-designs and identification of threshold were used. A two-stage Bayesian hierarchical model was performed to summarise the percent increase in mortality with a 1 degrees C temperature increase (or decrease) with 95% confidence intervals in hot (or cold) days, with lagged effects also measured. Fifteen studies met the eligibility criteria and almost 13 million elderly deaths were included in this meta analysis. In total, there was a 2-5% increase for a 1 degrees C increment during hot temperature intervals, and a 1-2 % increase in all-cause mortality for a 1 degrees C decrease during cold temperature intervals. Lags of up to 9 days in exposure to cold temperature intervals were substantially associated with all cause mortality, but no substantial lagged effects were observed for hot intervals. Thus, both hot and cold temperatures substantially increased mortality among the elderly, but the magnitude of heat-related effects seemed to be larger than that of cold effects within a global context. PMID- 21975974 TI - Institute of medicine committee report on resident duty hours: a view from a trench. AB - BACKGROUND: In late 2008, the Institute of Medicine (IOM) published a report recommending more restrictive limits on resident work hours to promote patient safety. Reaction from the graduate medical education community has focused on concerns about a lack of evidence supporting the IOM's recommendations. We highlight 3 concerns with the report: 1) a disproportionate attention to resident fatigue when changes in other areas may have a larger impact on patient safety. Data supporting a causal link between resident fatigue and medical errors that harm patients are not robust. Two areas where data support a stronger impact on patient safety include resident supervision and transitions of care; 2) a "one size fits all" model when specialty-specific recommendations may be more appropriate. For example, 16 hours on task is not at all similar for residents in different specialties (ie, surgery and primary care); and 3) the absence of a process to evaluate the impact of current or potential duty hour requirements on outcomes. Because these potential impacts have not been sufficiently researched, it is premature to support additional changes at this time. RECOMMENDATIONS: TO MOVE FORWARD IN A COMPREHENSIVE MANNER, WE RECOMMEND THE FOLLOWING: 1) support more research to evaluate the effects of duty hours in conjunction with other interrelated factors on patient safety, 2) encourage individual Accreditation Council for Graduate Medical Education (ACGME) Review committees to develop specialty specific duty hour limitations, and 3) develop partnerships between the IOM, ACGME, and the institutions directly involved with medical education to study how to maximize patient safety while maintaining quality educational outcomes. PMID- 21975975 TI - Failure to thrive: pediatric residents weigh in on feasibility trial of the proposed 2008 institute of medicine work hour restrictions. AB - BACKGROUND: In December 2008 the Institute of Medicine (IOM) released a report recommending limits on resident hours that are considerably more restrictive than the current Accreditation Council for Graduate Medical Education duty hour standards. INTERVENTION: In March 2009, a large pediatric residency program implemented a 1-month trial of a schedule and team structure fully congruent with the IOM recommendations to study the implications of such a schedule. METHODS: Comparison of the interns' experience in the trialed intervention schedule was made to interns working a traditional schedule with every fourth night call. RESULTS: The residents on the intervention schedule averaged 7.8 hours of sleep per 24-hour period compared to 7.6 hours for interns in a traditional schedule. Participation in bedside rounds and formal didactic conferences was decreased in the intervention schedule. Several factors contributed to increased perceived work intensity for interns in the intervention schedule. Redistribution of work during busy shifts altered the role of senior residents and attending physicians which may have a negative effect on senior residents' ability to develop skills as supervisors and educators. CONCLUSIONS: The trial implementation suggests it is possible to implement the proposed duty hour limits in a pediatric residency, but it would require a significant increase in the resident workforce (at least 25% and possibly 50%) to care for the same number of patients. Furthermore, the education model would need to undergo significant changes. Further trials of the IOM recommendations are needed prior to widespread implementation in order to learn what works best and causes the least harm, disruption, and unnecessary cost to the system. PMID- 21975976 TI - One possible future for resident hours: interns' perspective on a one-month trial of the institute of medicine recommended duty hour limits. AB - BACKGROUND: In December 2008, the Institute of Medicine (IOM) released the report of a consensus committee recommending added limits on resident duty hours. METHODS: Perceptions of interns participating in a 1-month trial implementation of the IOM-recommended duty hour limits in one large pediatric residency program during March 2009 were aggregated. RESULTS: Interns experienced benefits from the shift-based schedule, including reduced hours and more nights at home. These were accompanied by shortcomings of the new schedule, most prominently increased intensity during the hours worked, weaknesses in sign-outs and handing off of tasks, and inability to know and "own" all patients on the interns' team. The experiment also changed the role and the level of engagement expected from attending physicians. CONCLUSIONS: The trial implementation of the IOM recommended limits highlighted that to adapt to additional reduction in hours, residency education needs a significant culture change, including better sign outs, improved organization of bedside and didactic education, and attention to the added work intensity of a team-based model with daily admissions. Ultimately this may require an adjustment in residents' workload and different expectations and models of support from attending physicians. PMID- 21975977 TI - Toward a new paradigm in graduate medical education in the United States: elimination of the 24-hour call. AB - BACKGROUND: Sleep deprivation negatively affects resident performance, education, and safety. Concerns over these effects have prompted efforts to reduce resident hours. This article describes the design and implementation of a scheduling system with no continuous 24-hour calls. Aims included meeting Accreditation Council for Graduate Medical Education work hour requirements without increasing resident complement, maximizing continuity of learning and patient care, maintaining patient care quality, and acceptance by residents, faculty, and administration. METHODS: Various coverage options were formulated and discussed. The final schedule was the product of consensus. After re-engineering the master rotation schedule, service-specific conversion of on-call schedules was initiated in July 2003 and completed in July 2004. Annual in-training and certifying examination performance, length of stay, patient mortalities, resident motor vehicle accidents/near misses, and resident satisfaction with the new scheduling system were tracked. RESULTS: Continuous 24-hour call has been eliminated from the program since July 2004, with the longest assigned shift being 14 hours. Residents have at least 1 free weekend per month, a 10-hour break between consecutive assigned duty hours, and a mandatory 4-hour "nap" break if assigned a night shift immediately following a day shift. Program-wide, duty hours average 66 hours per week for first-year residents, 63 hours per week for second-year residents, and 60 hours per week for third-year residents. Self-reported motor vehicle accidents and/or near misses of accidents significantly decreased (P < .001) and resident satisfaction increased (P = .42). The change was accomplished at no additional cost to the institution and with no adverse patient care or educational outcomes. CONCLUSIONS: Pediatric residency training with restriction to 14 consecutive duty hours is effective and well accepted by stakeholders. Five years later, the re-engineered schedule has become the new "normal" for our program. PMID- 21975978 TI - Impact of proposed institute of medicine duty hours: family medicine residency directors' perspective. AB - PURPOSE: To examine the opinions of family medicine residency program directors concerning the potential impact of the Institute of Medicine (IOM) resident duty hour recommendations on patient care and resident education. METHODS: A survey was mailed to 455 family medicine residency program directors. Data were summarized and analyzed using Epi Info statistical software. Significance was set at the P < .01 level. RESULTS: A total of 265 surveys were completed (60.9% response rate). A majority of family medicine residency program directors disagreed or strongly disagreed that the recent IOM duty hour recommendations will, in general, result in improved patient safety and resident education. Further, a majority of respondents disagreed or strongly disagreed that the proposed IOM rules would result in residents becoming more compassionate, more effective family physicians. CONCLUSION: A majority of family medicine residency program directors believe that the proposed IOM duty hour recommendations would have a primarily detrimental effect on both patient care and resident education. PMID- 21975979 TI - Work hour regulations: do we need further changes now? A survey of internal medicine faculty and residents. AB - BACKGROUND: In 2003, the Accreditation Council for Graduate Medical Education standardized and regulated work hours for physicians in training in the United States. In December 2008, the Institute of Medicine (IOM) recommended further reductions in duty hours to ensure safer conditions for patients and residents and fellows. Significantly, the IOM committee acknowledged that there are barriers to implementing its recommendations. METHODS: IN THE WAKE OF THE IOM PROPOSALS, WE CHOSE TO SURVEY A REFERENCE CLOSER TO HOME: residency program directors, faculty, and residents. Our survey allowed them the opportunity to express their opinions regarding the IOM proposals. RESULTS: The majority of the faculty oppose the proposed IOM changes, arguing that there is no definite evidence to support the hypothesis that fewer work hours mean better outcomes in patient safety and education. First-year residents and residents who moonlight were more likely to experience stress and to support decreased work hours. CONCLUSIONS: The thoughts and opinions of faculty and residents collected through this survey, in combination with evidence-based studies from trial implementation of these standards, will contribute real answers to the challenging questions on resident work hours. PMID- 21975980 TI - Residents' perceptions of their own professionalism and the professionalism of their learning environment. AB - BACKGROUND: The competency of professionalism encompasses a range of behaviors in multiple domains. Residency programs are struggling to integrate and effectively assess professionalism. We report results from a survey assessing residents' perceptions of their professional competence and the professionalism of their learning environment. METHODS: A survey was developed to assess specific behaviors reflecting professionalism based on the conceptualizations of key accrediting bodies. Residents rated their ability to perform the behaviors and reported the frequency with which they observed their fellow residents failing to perform the behaviors. Eighty-five senior residents in emergency medicine, internal medicine, pediatrics, psychiatry, and surgery specialties completed the survey (response rate = 77%). Differences among domains (and among items within domains) were assessed. Correlations between perceived professionalism and the professionalism of the learning environment were described. RESULTS: Cronbach alpha for professionalism competence was .93 and for professionalism in the learning environment it was .86. Residents reported feeling most competent in being accountable (mean score = 51.4%; F = 10.3, p<.001) and in demonstrating respect. Some residents reported having trouble being sensitive to patients (n = 5 to 23). Disrespectful behaviors were the most frequently witnessed professionalism lapse in the learning environment (mean = 41.1%; F = 8.1, p<.001). While serious lapses in professionalism were not witnessed with great frequency in the learning environment, instances of over-representing qualifications were reported. Problems in accountability in the learning environment were negatively associated with residents' perceived competence. CONCLUSIONS: Residents reported being able to perform professionally most of the time, especially in terms of accountability and respect. However, disrespect was a feature of the learning environment for many residents and several serious lapses were witnessed by a small number of residents. Accountability in the learning environment may be an important indicator of or influence on residents' professionalism. PMID- 21975981 TI - Evaluating professionalism and interpersonal and communication skills: implementing a 360-degree evaluation instrument in an anesthesiology residency program. AB - OBJECTIVES: To implement a 360-degree resident evaluation instrument on the postanesthesia care unit (PACU) rotation and to determine the reliability, feasibility, and validity of this tool for assessing residents' professionalism and interpersonal and communication skills. METHODS: Thirteen areas of evaluation were selected to assess the professionalism and interpersonal and communication skills of residents during their PACU rotation. Each area was measured on a 9 point Likert scale (1, unsatisfactory performance, to 9, outstanding performance). Rating forms were distributed to raters after the completion of the PACU rotation. Raters included PACU nurses, secretarial staff, nurse aides, and medical technicians. Residents were aware of the 360-degree assessment and participated voluntarily. The multiple raters' evaluations were then compared with those of the traditional faculty. Intraclass correlation coefficients were calculated to measure the reliability of ratings within each category of raters by the Pearson correlation coefficient. RESULTS: Four hundred twenty-nine rating forms were returned during the study period. Fifteen residents were evaluated. The response rate was 88%. Residents were ranked highest on availability and lowest on management skill. The average rating across all areas was high (8.23). The average mean rating across all items from PACU nurses was higher (8.34) than from secretarial staff (7.99, P > .08). The highest ranked resident ranked high with all raters and the lowest ranked was low with most raters. The intraclass coefficients of correlations were 0.8719, 0.7860, 0.8268, and 0.8575. CONCLUSIONS: This type of resident assessment tool may be useful for PACU rotations. It appears to correlate with traditional faculty ratings, is feasible to use, and provides formative feedback to residents regarding their professionalism and interpersonal and communication skills. PMID- 21975982 TI - Residents' perspectives on professionalism. AB - BACKGROUND: Research defining professionalism exists, yet little is known about how residents view this important attribute for medical practice. Knowing more about residents' interpretations of professionalism and about how they value professionalism would enhance definitions and facilitate support for the development of professionalism skills and behaviors at the graduate level. PURPOSE: The purpose of this phenomenological study was to investigate how residents think about professionalism, how they value it, and how it plays out in their educational lives. METHODS: This study uses qualitative methods, employing 5 focus groups representative of a range of disciplines. Methods include providing unstructured prompts, member checking and informant feedback to support credibility, and content analysis to discern significant patterns. RESULTS: Content analysis supported that residents highly value professionalism and see it as a complex construct, dependent on the situation, discipline, and on personal experience. Challenges to professionalism are common in graduate medical education and a great concern for residents. CONCLUSIONS: Physician educators often discuss professionalism as an overarching concept in medicine, especially in classes during the preclinical years. Although some general principles are applicable, residents relate more deeply to aspects of professionalism that concern their own clinical practice, situation, and specialty. Implications for measurement of professional skills and for further research are included in this report. PMID- 21975983 TI - Changing the Conversation From Burnout to Wellness: Physician Well-being in Residency Training Programs. AB - BACKGROUND: The existing literature either does not address physician wellness or defines it as a lack of burnout. The goal of this article is to call attention to this important gap in the literature and provide ideas for how to fill it. We need a culture change, and we propose that this change begin within graduate medical education. METHODS: We describe a case example of culture change and definitions of wellness at William Beaumont Hospitals, Troy Family Medicine Residency Program, a community-based, university-affiliated program in suburban Detroit, Michigan. RESULTS: We developed a toolbox of practical steps to create a culture that emphasizes wellness. We present a general timeline illustrating necessary steps toward accomplishing a true cultural change. DISCUSSION: The time has come for academic medicine to move beyond a simple discussion of physician burnout. To do this, we must first develop a shared definition of physician wellness followed by interventional strategies to bolster it. The benefits of cultural change include providing a more positive educational environment for residents and faculty, raising awareness of burnout and its symptoms, decreasing the stigma associated with admitting burnout symptoms, enabling the development of prevention strategies, and creating a more positive, strength-based approach to understanding the toll of physician-patient relationships on physicians. PMID- 21975984 TI - Burnout, psychological skills, and empathy: balint training in obstetrics and gynecology residents. AB - OBJECTIVES: To assess burnout, behavioral-medicine skills, and empathy among obstetrics and gynecology residents before and after implementation of Balint training. METHODS: This was a prospective educational study. Balint training was introduced into the obstetrics and gynecology residency curriculum in July 2005. All 36 residents were approached for this study. The Psychological Medicine Inventory, the Maslach Burnout Inventory, and the Jefferson Scale of Physician Empathy were administered prior to initiating training and at 12 months. Baseline and 12-month scores were compared by Wilcoxon signed rank test. RESULTS: Seventeen residents completed baseline and 12-month questionnaires: 6 were postgraduate year (PGY) 1, 3 were PGY-2, 6 were PGY-3, and 2 were PGY-4. At baseline, 70% of participating residents reported high burnout scores. Burnout and empathy remained unchanged at 12 months. Psychological medicine skills improved at 12 months. CONCLUSIONS: This study showed that obstetrics and gynecology residents are at high risk for burnout. Interest and confidence in handling psychological aspects of patient care improved at 12 months after the introduction of Balint training. PMID- 21975986 TI - Integrating Teamwork into the "DNA" of Graduate Medical Education: Principles for Simulation-Based Training. PMID- 21975985 TI - Burnout during residency training: a literature review. AB - OBJECTIVE: Burnout is a state of mental and physical exhaustion related to work or care giving activities. Burnout during residency training has gained significant attention secondary to concerns regarding job performance and patient care. This article reviews the relevant literature on burnout in order to provide information to educators about its prevalence, features, impact, and potential interventions. METHODS: Studies were identified through a Medline and PsychInfo search from 1974 to 2009. Fifty-one studies were identified. Definition and description of burnout and measurement methods are presented followed by a thorough review of the studies. RESULTS: An examination of the burnout literature reveals that it is prevalent in medical students (28%-45%), residents (27%-75%, depending on specialty), as well as practicing physicians. Psychological distress and physical symptoms can impact work performance and patient safety. Distress during medical school can lead to burnout, which in turn can result in negative consequences as a working physician. Burnout also poses significant challenges during early training years in residency. Time demands, lack of control, work planning, work organization, inherently difficult job situations, and interpersonal relationships, are considered factors contributing to residents' burnout. Potential interventions include workplace-driven and individual-driven measures. Workplace interventions include education about burnout, workload modifications, increasing the diversity of work duties, stress management training, mentoring, emotional intelligence training, and wellness workshops. Individual-driven behavioral, social, and physical activities include promoting interpersonal professional relations, meditation, counseling, and exercise. CONCLUSIONS: Educators need to develop an active awareness of burnout and ought to consider incorporating relevant instruction and interventions during the process of training resident physicians. PMID- 21975987 TI - Simulation for the training of human performance and technical skills: the intersection of how we will train health care professionals in the future. AB - AIMS: The aims of this research are to begin to understand health care teams in their operational environment, establish metrics of performance for these teams, and validate a series of scenarios in simulation that elicit team and technical skills. The focus is on defining the team model that will function in the operational environment in which health care professionals work. METHODS: Simulations were performed across the United States in 70- to 1000-bed hospitals. Multidisciplinary health care teams analyzed more than 300 hours of videos of health care professionals performing simulations of team-based medical care in several different disciplines. Raters were trained to enhance inter-rater reliability. RESULTS: The study validated event sets that trigger team dynamics and established metrics for team-based care. Team skills were identified and modified using simulation scenarios that employed the event-set-design process. Specific skills (technical and team) were identified by criticality measurement and task analysis methodology. DISCUSSION: In situ simulation, which includes a purposeful and Socratic Method of debriefing, is a powerful intervention that can overcome inertia found in clinician behavior and latent environmental systems that present a challenge to quality and patient safety. In situ simulation can increase awareness of risks, personalize the risks, and encourage the reflection, effort, and attention needed to make changes to both behaviors and to systems. PMID- 21975988 TI - Team behavior during trauma resuscitation: a simulation-based performance assessment. AB - INTRODUCTION: Trauma resuscitations require a coordinated response from a diverse group of health care providers. Currently, there are no widely accepted methods of assessing team effectiveness in this setting. Simulation affords a method to assess team effectiveness. The purpose of this study was to use a simulation setting to develop a specialized assessment instrument for team response in trauma resuscitation. METHODS: We developed our assessment instrument using clinical simulation. Four teams of 3 postgraduate year-2 surgical trainees in conjunction with scripted confederates were videotaped enacting 6 separate trauma resuscitation scenarios that mirrored clinical conditions encountered at our level 1 trauma center. Ten of the resulting videotaped scenarios represented a spectrum of team behavior (ineffective to effective) and were scored by 8 experienced clinicians using the Mayo High Performance Teamwork Scale. RESULTS: Based in part on the Mayo High Performance Teamwork Scale, we created a prototype trauma team assessment tool consisting of 7 attributes that we scored in binary fashion (present/absent). We validated this prototype by assigning a normalized ranking score to each of the 10 scenarios based on the score supplied by each rater. The presence/absence of the 7 attributes varied significantly among scenarios (52.5% to 93.8%; P < .001). Median scores differed significantly comparing the 5 lowest-ranking scenarios with the 5 highest-ranking scenarios (P < .001). CONCLUSION: Our prototype instrument may be effective at assessing team effectiveness during trauma resuscitations. This instrument may prove useful for assessing team competency skills, providing timely feedback to teams, and examining the relationship between effective team function and clinically important outcomes. Further, it may be applicable to other high-acuity, time sensitive clinical situations. PMID- 21975989 TI - Use of a postpartum hemorrhage simulator for instruction and evaluation of residents. AB - OBJECTIVE: Postpartum hemorrhage is a common and potentially life-threatening obstetric emergency. We sought to create a realistic simulation and validate a standardized grading form to evaluate competency in the management of postpartum hemorrhage. METHODS: Residents from 3 programs underwent training with a postpartum hemorrhage simulation using a standard obstetric birthing model equipped with an inflatable uterus to simulate uterine atony. All simulations were graded by staff physicians with a standardized grading sheet constructed from the current literature on the topic. Residents were expected to recognize the hemorrhage and take appropriate steps, including asking the assistant to administer medications, to correct the problem. Objective and subjective performance was measured with standardized grading sheets, and results were analyzed for reliability using Cronbach alpha and intraclass correlation coefficients. This project was conducted in accordance with the hospital Institutional Review Board policies at each institution. RESULTS: Forty residents from 3 institutions underwent simulation training. The majority were unable to correct the hemorrhage within 5 minutes and almost half also made at least 1 error, either the dose or route, in the medications they requested. Reliability was evaluated with Cronbach alpha and demonstrated the grading sheets were valid and had good interrater reliability. DISCUSSION: A simulated postpartum hemorrhage scenario can identify important deficiencies in resident knowledge and performance, with no risk to patients. The standardized grading form worked well for our purposes and was reliable in our study. Further testing is needed to evaluate whether the training improves performance in real-life hemorrhages. PMID- 21975990 TI - Grommets and glue guns: standardization of a pfannenstiel model for low-fidelity obstetrics-gynecology education. AB - OBJECTIVE: To validate standardized instructions for the creation, implementation, and performance assessment of a low-fidelity model for Pfannenstiel incision. STUDY DESIGN: The Pfannenstiel model used at the University of Florida-Jacksonville was broken down into composite steps and constructed by obstetrics-gynecology faculty from across the country. The model was then utilized at participants' home institutions and evaluated with respect to realism of the model, ability to replicate the simulation, appropriateness of the skills checklists, and perceived utility of a publication of similarly catalogued simulation modules for use in obstetrics-gynecology training programs. RESULTS: The model was correctly constructed by 94.7% (18 of 19) participants and 72.2% (13 of 18) completed a post construction/post simulation survey indicating a high degree of perceived educational utility, feasibility of construction, and desire for additional catalogued modules. CONCLUSIONS: A low-fidelity simulation model was developed, successfully reproduced using inexpensive materials, and implemented across multiple training programs. This model can serve as a template for developing, standardizing and cataloging other low-fidelity simulations for use in resident education. As discussions among medical educators continue regarding further restrictions on duty hours, it is highly likely that more programs will be looking for guidance in establishing quick, inexpensive, and reliable means of developing and assessing surgical skills in their learners. Furthermore, the Accreditation Council for Graduate Medical Education (ACGME) has well-defined goals of programs developing better and more reproducible tools for all of their assessments. For programs with limited resources, preparing and disseminating reproducible, validated tools could be invaluable in complying with future ACGME mandates. PMID- 21975991 TI - Creating a common patient safety denominator: the interns' course. AB - AIM: After finishing medical school, interns are in many ways unprepared for handling patient care challenges independently. Recognizing that interns may benefit from a patient safety orientation, we developed an innovative curriculum to impart competencies related to their role in preventing medical errors. In the course, which runs during the first week of the intern year, we specifically address 1) calling for help; 2) teamwork and communication; 3) hand hygiene compliance; and, 4) preventing medication and other system errors. METHODS: The course consists of a lecture, interactive workshop, and a Web-based didactic component. Small-group simulation sessions allow instructors to assess interns' baseline competence in hand hygiene and patient hand-offs. In an individual exercise, interns performed a directed physical exam on a standardized patient and their hand hygiene adherence was recorded. In a group exercise, team performance was evaluated in accepting a hand-off from another provider and managing a deteriorating patient. RESULTS: Of the 131 interns, 35% (41) did not wash their hands before and 95% (121) did not wash their hands after patient examination. In the team exercise, scores for 23 teams ranged from 8 to 18 out of 30. None of the participants asked for additional information prior to accepting responsibility for the patient, despite a clearly inadequate hand-off. Post course surveys indicate that interns consider the course worthwhile: 95% (121) found it beneficial, acquired new teamwork skills, had more appreciation for patient safety, and felt better prepared for clinical duties. DISCUSSION: We observed serious gaps in hand-hygiene compliance and in communication during hand offs, both significant impediments to quality patient care. Nevertheless, positive responses to the course from both the interns and the institution reflect an important step in fostering a culture of patient safety. PMID- 21975992 TI - Components of Critical Decision Making and ABSITE Assessment: Toward a More Comprehensive Evaluation. AB - RATIONALE: Accurate assessment of resident competency is a fundamental requisite to assure the training of physicians is adequate. In surgical disciplines, structured tests as well as ongoing evaluation by faculty are used for evaluating resident competency. Although structured tests evaluate content knowledge, faculty ratings are a better measure of how that knowledge is applied to real world problems. In this study, we sought to explore the performance of surgical residents in a simulation exercise (strategic management simulations [SMS]) as an objective surrogate of real-world performance. METHODS: Forty surgical residents participated in the SMS simulation that entailed decision making in a real-world oriented task situation. The task requirements enable the assessment of decision making along several parameters of thinking under both crisis and noncrisis situations. Performance attributes include "simpler" measures of competency (activity level), intermediate categories (information management and emergency responses) to complex measures (breadth of approach and strategy). Scores obtained in the SMS were compared with the scores obtained on the American Board of Surgery In-Training Examination (ABSITE). RESULTS: The data were intercorrelated and subjected to a multiple regression analysis with ABSITE as the dependent variable and simulation scores as independent variables. Using a 1 tail test analysis, only 3 simulation variables correlated with performance on ABSITE at the .01 level (ie, basic activity, focused activity, task orientation). Other simulation variables showed no meaningful relationships to ABSITE scores at all. CONCLUSIONS: The more complex real-world-oriented decision-making parameters on SMS did not correlate with ABSITE scores. We believe that techniques such as the SMS, which focus on critical thinking, complement assessment of medical knowledge using ABSITE. The SMS technique provides an accurate measure of real world performance and provides objective validation of faculty ratings. PMID- 21975993 TI - Advancing resident assessment in graduate medical education. AB - BACKGROUND: The Outcome Project requires high-quality assessment approaches to provide reliable and valid judgments of the attainment of competencies deemed important for physician practice. INTERVENTION: The Accreditation Council for Graduate Medical Education (ACGME) convened the Advisory Committee on Educational Outcome Assessment in 2007-2008 to identify high-quality assessment methods. The assessments selected by this body would form a core set that could be used by all programs in a specialty to assess resident performance and enable initial steps toward establishing national specialty databases of program performance. The committee identified a small set of methods for provisional use and further evaluation. It also developed frameworks and processes to support the ongoing evaluation of methods and the longer-term enhancement of assessment in graduate medical education. OUTCOME: The committee constructed a set of standards, a methodology for applying the standards, and grading rules for their review of assessment method quality. It developed a simple report card for displaying grades on each standard and an overall grade for each method reviewed. It also described an assessment system of factors that influence assessment quality. The committee proposed a coordinated, national-level infrastructure to support enhancements to assessment, including method development and assessor training. It recommended the establishment of a new assessment review group to continue its work of evaluating assessment methods. The committee delivered a report summarizing its activities and 5 related recommendations for implementation to the ACGME Board in September 2008. PMID- 21975994 TI - Mapping cognitive overlaps between practice-based learning and improvement and evidence-based medicine: an operational definition for assessing resident physician competence. AB - PURPOSE: The complex competency labeled practice-based learning and improvement (PBLI) by the Accreditation Council for Graduate Medical Education (ACGME) incorporates core knowledge in evidence-based medicine (EBM). The purpose of this study was to operationally define a "PBLI-EBM" domain for assessing resident physician competence. METHOD: The authors used an iterative design process to first content analyze and map correspondences between ACGME and EBM literature sources. The project team, including content and measurement experts and residents/fellows, parsed, classified, and hierarchically organized embedded learning outcomes using a literature-supported cognitive taxonomy. A pool of 141 items was produced from the domain and assessment specifications. The PBLI-EBM domain and resulting items were content validated through formal reviews by a national panel of experts. RESULTS: The final domain represents overlapping PBLI and EBM cognitive dimensions measurable through written, multiple-choice assessments. It is organized as 4 subdomains of clinical action: Therapy, Prognosis, Diagnosis, and Harm. Four broad cognitive skill branches (Ask, Acquire, Appraise, and Apply) are subsumed under each subdomain. Each skill branch is defined by enabling skills that specify the cognitive processes, content, and conditions pertinent to demonstrable competence. Most items passed content validity screening criteria and were prepared for test form assembly and administration. CONCLUSIONS: The operational definition of PBLI-EBM competence is based on a rigorously developed and validated domain and item pool, and substantially expands conventional understandings of EBM. The domain, assessment specifications, and procedures outlined may be used to design written assessments to tap important cognitive dimensions of the overall PBLI competency, as given by ACGME. For more comprehensive coverage of the PBLI competency, such instruments need to be complemented with performance assessments. PMID- 21975995 TI - Utilizing quality improvement methods to improve patient care outcomes in a pediatric residency program. AB - OBJECTIVE: Although there is an expectation for outcomes-oriented training in residency programs, the reality is that few guidelines and examples exist as to how to provide this type of education and training. We aimed to improve patient care outcomes in our pediatric residency program by using quality improvement (QI) methods, tools, and approaches. METHODS: A series of QI projects were implemented over a 3-year period in a pediatric residency program to improve patient care outcomes and teach the residents how to use QI methods, tools, and approaches. Residents experienced practice-based learning and systems-based assessment through group projects and review of their own patient outcomes. Resident QI experiences were reviewed quarterly by the program director and were a mandatory part of resident training portfolios. RESULTS: Using QI methodology, we were able to improve management of children with obesity, to achieve high compliance with the national patient safety goals, improve the pediatric hotline service, and implement better patient flow in resident continuity clinic. CONCLUSION: Based on our experiences, we conclude that to successfully implement QI projects in residency programs, QI techniques must be formally taught, the opportunities for resident participation must be multiple and diverse, and QI outcomes should be incorporated in resident training and assessment so that they experience the benefits of the QI intervention. The lessons learned from our experiences, as well as the projects we describe, can be easily deployed and implemented in other residency programs. PMID- 21975996 TI - Medical-legal partnerships: addressing competency needs through lawyers. AB - BACKGROUND: Many low- and moderate-income individuals and families have at least one unmet legal need (for example, unsafe housing conditions, lack of access to food and/or income support, lack of access to health care), which, if left unaddressed, can have harmful consequences on health. Eighty unique medical-legal partnership programs, serving over 180 clinics and hospitals nationwide, seek to combine the strengths of medical and legal professionals to address patients' legal needs before they become crises. Each partnership is adapted to serve the specific needs of its own patient base. INTERVENTION: This article describes innovative, residency-based medical-legal partnership educational experiences in pediatrics, internal medicine, and family medicine at 3 different sites (Boston, Massachusetts; Newark, New Jersey; and Tucson, Arizona). This article addresses how these 3 programs have been designed to meet the Accreditation Council for Graduate Medical Education's 6 competencies, along with suggested methods for evaluating the effectiveness of these programs. Training is a core component of medical-legal partnership, and most medical-legal partnerships have developed curricula for resident education in a variety of formats, including noon conferences, grand rounds, poverty simulations and day-long special sessions. DISCUSSION: Medical-legal partnerships combine the skill sets of medical professionals and lawyers to teach social determinants of health by training residents and attending physicians to identify and help address unmet legal needs. Medical-legal partnership doctors and lawyers treat health disparities and improve patient health and well-being by ensuring that public programs, regulations, and laws created to benefit health and improve access to health care are implemented and enforced. PMID- 21975997 TI - Effect of number of clinics and panel size on patient continuity for medical residents. AB - BACKGROUND: Accreditation Council for Graduate Medical Education program requirements for internal medicine residency training include a longitudinal, continuity experience with a panel of patients. OBJECTIVE: To determine whether the number of resident clinics, the resident panel size, and the supervising attending physician affect patient continuity. To determine the number of clinics and the panel size necessary to maximize patient continuity. DESIGN: We used linear regression modeling to assess the effect of number of attended clinics, the panel size, and the attending physician on patient continuity. PARTICIPANTS: Forty medicine residents in an academic medicine clinic. MEASUREMENTS: Percent patient continuity by the usual provider of care method. RESULTS: Unadjusted linear regression analysis showed that patient continuity increased 2.3% +/- 0.7% for each additional clinic per 9 weeks or 0.4% +/- 0.1% for each additional clinic per year (P = .003). Conversely, patient continuity decreased 0.7% +/- 0.4% for every additional 10 patients in the panel (P = .04). When simultaneously controlling for number of clinics, panel size, and attending physician, multivariable linear regression analysis showed that patient continuity increased 3.3% +/- 0.5% for each additional clinic per 9 weeks or 0.6% +/- 0.1% for each additional clinic per year (P < .001). Conversely, patient continuity decreased 2.2% +/- 0.4% for every additional 10 patients in the panel (P < .001). Thus, residents who actually attend at least 1 clinic per week with a panel size less than 106 patients can achieve 50% patient continuity. Interestingly, the attending physician accounted for most of the variability in patient continuity (51%). CONCLUSIONS: Patient continuity for residents significantly increased with increasing numbers of clinics and decreasing panel size and was significantly influenced by the attending physician. PMID- 21975998 TI - Expanding the SOAP Note to SOAPS (With S for Safety): A New Era in Real-time Safety Education. AB - The challenges inherent in medical education are multiple, including recognition of different learning styles among students, incorporation of the Accreditation Council for Graduate Medical Education competencies and outcomes measurement into the curriculum, and compliance with mandated duty hours along with a heightened awareness of patient safety required by our regulatory institutions. With the requirement that safety become an explicit part of the residency curriculum across all specialties, educators are charged with innovative ways of achieving this goal. The following commentary addresses this need and suggests an innovative approach to the traditional daily rounds' SOAP (subjective, objective, assessment, and plan) note to incorporate a second S for safety. The use of a SOAPS note elevates each encounter by integrating quality and error avoidance as a component of care. This method teaches the next generation of physicians the importance of patient safety as an integral part of every doctor-patient interaction. PMID- 21975999 TI - The accreditation and certification system after next. PMID- 21976000 TI - Making sense: duty hours, work flow, and waste in graduate medical education. AB - Parsimony, and not industry, is the immediate cause of the increase of capital. Industry, indeed, provides the subject which parsimony accumulates. But whatever industry might acquire, if parsimony did not save and store up, the capital would never be the greater.Adam Smith, The Wealth of Nations, book 2, chapter 31In 2003, the Accreditation Council for Graduate Medical Education implemented resident duty hour limits that included a weekly limit and limits on continuous hours. Recent recommendations for added reductions in resident duty hours have produced concern about concomitant reductions in future graduates' preparedness for independent practice. The current debate about resident hours largely does not consider whether all hours residents spend in the educational and clinical care environment contribute meaningfully either to residents' learning or to effective patient care. This may distract the community from waste in the current clinical-education model. We propose that use of "lean production" and quality improvement methods may assist teaching institutions in attaining a deeper understanding of work flow and waste. These methods can be used to assign value to patient- and learner-centered activities and outputs and to optimize the competing and synergistic aspects of all desired outcomes to produce the care the Institute of Medicine recommends: safe, effective, efficient, patient-centered, timely, and equitable. Finally, engagement of senior clinical faculty in determining the culture of the care and education system will contribute to an advanced social-learning and care network. PMID- 21976001 TI - The ACGME Resident Survey Aggregate Reports: An Analysis and Assessment of Overall Program Compliance. AB - BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) uses a 29-question Resident Survey for yearly residency program assessments. This article describes methodology for aggregating Resident Survey data into 5 discrete areas of program performance for use in the accreditation process. This article also describes methodology for setting thresholds that may assist Residency Review Committees in identifying programs with potential compliance problems. METHODS: A team of ACGME staff and Residency Review Committee chairpersons reviewed the survey for content and proposed thresholds (through a modified Angoff procedure) that would indicate problematic program functioning. RESULTS: Interrater agreement was high for the 5 content areas and for the threshold values (percentage of noncompliant residents), indicating that programs above these thresholds may warrant follow-up by the accrediting organization. Comparison of the Angoff procedure and the actual distribution of the data revealed that the Angoff thresholds were extremely similar to 1 standard deviation above the content area mean. CONCLUSION: Data from the ACGME Resident Survey may be aggregated into internally consistent and consensually valid areas that may help Residency Review Committees make more targeted and specific judgments about program compliance. PMID- 21976002 TI - The 2003 common duty hour limits: process, outcome, and lessons learned. PMID- 21976003 TI - NLRP1 gene polymorphism influences gene transcription and is a risk factor for rheumatoid arthritis in han chinese. AB - OBJECTIVE: The inflammasome-related protein NLRP1/NALP1 has been implicated in the onset and progression of some autoimmune diseases. This study was undertaken to determine whether a polymorphism in the NLRP1 gene is associated with susceptibility to rheumatoid arthritis (RA) in Han Chinese and to assess the functional implications of this association. METHODS: RA patients (n = 190) and matched healthy controls (n = 190) residing in the city of Chengdu were genotyped for the NLRP1 promoter polymorphisms rs6502867 and rs878329. Genotyping for rs878329 was performed in a second set of subjects (n = 1,514) residing in the city of Chongqing. The effect of each polymorphism on NLRP1 transcription was evaluated by dual-luciferase assay, while the effect on DNA protein interaction was determined by electrophoretic mobility shift assay. Differential expression of NLRP1 in individuals with different genotypes was investigated by real-time quantitative polymerase chain reaction. RESULTS: The polymorphism rs878329, but not rs6502867, was associated with RA (odds ratio [OR] 0.83, P = 0.02 for the C allele; OR 0.42, P = 0.01 for the CC genotype). The GG genotype of rs878329 was the risk genotype for RA (OR 2.38) and had a runt-related transcription factor 1 binding site that up-regulated NLRP1 transcription. Individuals with the RA risk genotype GG had significantly higher NLRP1 messenger RNA levels than those with the CC genotype among the Han Chinese population. CONCLUSION: Our findings indicate that NLRP1 is associated with RA in Han Chinese. The G allele of rs878329 in the NLRP1 promoter up-regulates gene transcription and confers the risk of RA. PMID- 21976004 TI - Human umbilical cord Wharton's jelly stem cells and its conditioned medium support hematopoietic stem cell expansion ex vivo. AB - Bone marrow mesenchymal stromal cells (BMMSCs) have been used as feeder support for the ex vivo expansion of hematopoietic stem cells (HSCs) but have the limitations of painful harvest, morbidity, and risk of infection to the patient. This prompted us to explore the use of human umbilical cord Wharton's jelly MSCs (hWJSCs) and its conditioned medium (hWJSC-CM) for ex vivo expansion of HSCs in allogeneic and autologous settings because hWJSCs can be harvested in abundance painlessly, are proliferative, hypoimmunogenic, and secrete a variety of unique proteins. In the presence of hWJSCs and hWJSC-CM, HSCs put out pseudopodia-like outgrowths and became highly motile. Time lapse imaging showed that the outgrowths helped them to migrate towards and attach to the upper surfaces of hWJSCs and undergo proliferation. After 9 days of culture in the presence of hWJSCs and hWJSC-CM, MTT, and Trypan blue assays showed significant increases in HSC numbers, and FACS analysis generated significantly greater numbers of CD34(+) cells compared to controls. hWJSC-CM produced the highest number of colonies (CFU assay) and all six classifications of colony morphology typical of hematopoiesis were observed. Proteomic analysis of hWJSC-CM showed significantly greater levels of interleukins (IL-1a, IL-6, IL-7, and IL-8), SCF, HGF, and ICAM-1 compared to controls suggesting that they may be involved in the HSC multiplication. We propose that cord blood banks freeze autologous hWJSCs and umbilical cord blood (UCB) from the same umbilical cord at the same time for the patient for future ex vivo HSC expansion and cell-based therapies. PMID- 21976005 TI - Long-term impact of pretransplant and posttransplant diabetes mellitus on kidney transplant outcomes. AB - BACKGROUND: The aim of this study was to compare the impact of preexisting diabetes mellitus (pre-DM), posttransplant DM (PTDM), and non-DM on the long-term outcomes of renal transplant recipients (RTRs). METHODS: This is a retrospective observational cohort study of 427 RTRs who underwent transplantation from 1999 to 2008. Patients were divided into non-DM, pre-DM, and PTDM groups. The primary outcome was the composite of doubling of the serum creatinine (SCr) level, graft failure, or death. Secondary outcomes were biopsy-proven acute rejection (BPAR), biopsy-proven interstitial fibrosis and/or tubular atrophy (IF/TA), and individual components of the primary outcome. RESULTS: A total of 70 patients (16.4%) had pre-DM, 104 (24.2%) had PTDM, and 253 (59.3%) had non-DM. Kaplan Meier analysis indicated significant differences in the development of the primary outcome: p = 0.003 (log rank test). Relative to the non-DM group, the pre DM group had a 6.36-fold increased risk [95% confidence interval (CI) 2.43-16.33; p < 0.001), and the PTDM group had a 2.00-fold increased risk (95% CI 1.08-3.73; p = 0.029) for development of the primary outcome. Patients in the pre-DM group had 6.73-fold (95% CI 2.46-18.42; p < 0.001), 4.56-fold (95% CI 1.77-11.78; p = 0.002), and 13.95-fold (95% CI 2.96-65.75; p < 0.001) increased risks for the development of SCr doubling, biopsy-proven IF/TA, and death-censored graft failure, respectively. Patients in the PTDM group had a 2.09-fold (95% CI 1.10 3.99; p = 0.025), increased risk for the development of SCr doubling. CONCLUSIONS: The presence of pre-DM or PTDM significantly impaired kidney allograft outcome. PMID- 21976006 TI - No outcome differences between a laparoscopic and retroperitoneoscopic approach in synchronous bilateral adrenal surgery. AB - BACKGROUND: Two main approaches have been described for endoscopic adrenalectomy: the transperitoneal approach with the patient in the lateral decubitus position (LA) and the retroperitoneal approach with the patient in the prone position (ERA). The goal of the present study was to compare the results of LA and ERA for endoscopic bilateral synchronous adrenalectomy. PATIENTS AND METHODS: Between 1994 and 2008, 34 patients underwent bilateral synchronous adrenalectomy in two referral centers: 20 patients underwent LA in Pisa (group A), and 14 patients underwent ERA in Halle (group B). Sex, age, preoperative diagnosis, body mass index, preoperative medical treatments, diameter of glands, blood loss, operative time, complications, conversion, intensive care unit stay, day of first oral intake, length of postoperative recovery, histology report, and outcome were analyzed. RESULTS: There were 7 men and 13 women in group A and 6 men and 8 women in group B. Mean age was 48.1 years in group A and 38.9 years in group B. Body mass index was similar in the two groups. Diameters of the glands were larger in group A than in group B, at 61.1 versus 42.8 mm for the right side and 64.1 versus 37.4 mm for the left side. Mean hospital stay was longer in group B (8.2 versus 5.25 days; P = 0.002), whereas the intensive care unit stay was longer in group A (1.44 versus 1 day). CONCLUSIONS: It is not possible to determine which of the two approaches is better; both are feasible, safe, and effective and patient outcomes are almost the same. PMID- 21976007 TI - Anatomical variations of hepatic veins: three-dimensional computed tomography scans of 200 subjects. AB - BACKGROUND: The impact of hepatic venous anatomic variations on hepatic resection and transplantation is the least understood aspect of liver surgery. METHODS: A prospective three-dimensional computed tomography study was undertaken on 200 consecutive subjects with normal livers to determine the prevalence of surgically significant hepatic venous anatomic variations. RESULTS: The prevailing pattern of the three hepatic veins in these subjects was a right hepatic vein (RHV) and a common trunk for the middle (MHV) and left (LHV) hepatic veins (122/200, 61%). The remaining patients had the RHV, MHV, and LHV draining independently into the inferior vena cava (IVC). In 39% of patients, the RHV was small and was compensated by a large right inferior hepatic vein (21.0%), an accessory RHV (8.5%) or a well-developed MHV (6.5%). A segment 4 vein was seen in 51.5% of patients. This segment 4 vein joined the LHV (26%), the MHV (17.5%), or the IVC (8%). An umbilical vein and a segment 4 vein were seen in 3.5% of patients. These two veins joined either the LHV (2.0%) or the MHV (1.5%). CONCLUSIONS: Knowing the variations of hepatic veins before surgery is useful during both partial hepatectomy and donor operations for living related liver transplantation. PMID- 21976008 TI - Effect of perioperative intensive insulin therapy for liver dysfunction after hepatic resection. AB - BACKGROUND: Intensive insulin therapy (IIT) reduces morbidity and mortality in patients in surgical care units, yet the benefits of IIT during liver surgery, especially on liver function after hepatic resection, are not known. The aim of the present study was to assess the effects of IIT, with a focus on postoperative liver function, in hepatectomized patients. METHODS: A total of 150 patients who underwent surgical management for hepatic diseases between September 2007 and March 2009 at Kochi Medical School were investigated. Patients were divided into two groups: (1) those receiving IIT via a closed-loop glycemic control system (i.e., an artificial pancreas; AP group; n = 74); or (2) those receiving conventional insulin therapy using the sliding scale method (SS group; n = 76). The targeted blood glucose zones in the AP and SS groups were 80-110 and 150-200 mg/dl, respectively. RESULTS: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels increased and prothrombin time (%) decreased immediately after surgery in both groups. There was a significant difference in postoperative ALT levels between the two groups on postoperative days 1 and 6. Hepatocyte injury and changes in AST and ALT levels after surgery (compared with preoperative levels) were significantly greater in the SS group than AP group after liver resection. During the first 18 h after hepatic resection, 174 IU of insulin was required per patient for tight glycemic control with IIT. CONCLUSIONS: Perioperative IIT ameliorated liver dysfunction after hepatic resection. Liver regeneration and/or an antiinflammatory effect of IIT may underlie its protective effects against hepatocyte injury in hepatectomized patients. PMID- 21976009 TI - Cytoplasmic Forkhead box M1 (FoxM1) in esophageal squamous cell carcinoma significantly correlates with pathological disease stage. AB - Esophageal cancer is a deadly cancer with esophageal squamous cell carcinoma (ESCC) as the major type. Until now there has been a lack of reliable prognostic markers for this malignancy. This study aims to investigate the clinical correlation between Forkhead box M1 (FoxM1)and patients' parameters in ESCC. METHODS: Immunohistochemistry was performed to investigate the expression and localization of FoxM1 in 64ESCC tissues and 10 nontumor esophageal tissues randomly selected from 64 patients before these data were used for clinical correlations. RESULTS: Cytoplasmic and nuclear expressions of FoxM1 were found in 63 and 16 of the 64 ESCC tissues, respectively.Low cytoplasmic expression of FoxM1 was correlated with early pathological stage in ESCC (P = 0.018),while patients with nuclear FoxM1 were younger in age than those without nuclear expression (P?0.001).Upregulation of FoxM1 mRNA was found in five ESCCcell lines (HKESC-1, HKESC-2, HKESC-3, HKESC-4,and SLMT-1) when compared to non-neoplastic esophageal squamous cell line NE-1 using quantitative polymerase chain reaction (qPCR). Except for HKESC-3, all studied ESCC cell lines demonstrated a high expression of FoxM1 protein using immunoblot. A high mRNA level of FoxM1 was observed in all of the ESCC tissues examined when compared to their adjacent nontumor tissues using qPCR. CONCLUSION: Cytoplasmic FoxM1 was correlated with pathological stage and might be a biomarker for advanced ESCC. PMID- 21976010 TI - Candida peritonitis: an update on the latest research and treatments. PMID- 21976011 TI - Enterocutaneous fistulas and a hostile abdomen: reoperative surgical approaches. AB - Damage-control surgery and open-abdomen is an acceptable-and often lifesaving approach to the treatment of patients with severe trauma, abdominal compartment syndrome, necrotizing soft tissue catastrophes, and other abdominal disasters, when closing the abdomen is not possible, ill advised, or will have serious sequelae. However, common consequences of open-abdomen management include large abdominal wall defects, enterocutaneous fistulas (ECFs), and enteroatmospheric fistulas (EAFs). Furthermore, in such patients, a frozen and hostile abdomen (alone or combined with ECFs) is not uncommon. Adding biologic mesh to our surgical armamentarium has revolutionized hernia surgery. PMID- 21976012 TI - Preservation of genital innervation in women during total mesorectal excision: which anterior plane? AB - BACKGROUND: Erectile dysfunction, principally related to injury of the autonomic nerve fibers in men, is a major cause of postoperative morbidity after anterolateral dissection during total mesorectal excision (TME) for rectal adenocarcinoma. However, the autonomic innervation of erectile bodies is less known in women, and the anterolateral plane of dissection during TME remains unclear. The existence of the rectovaginal septum(RVS) is controversial. The purpose of the present study was to identify the RVS in the human fetus and adult female by dissection, immunohistochemistry, and three-dimensional reconstruction, and to define its relationship with erectile nerve fibers so as to determine the anterolateral plane of dissection during TME, which could reduce postoperative sexual dysfunction in women. METHOD: Macroscopic dissection, histologic studies, and immunohistochemistry examination with 3D reconstruction were performed in six fresh female adult cadavers and six female fetuses. RESULTS: The RVS was clearly definable in all adult specimens. It was composed of multiple connective tissue, with smooth muscle fibers originating from the uterus and the vagina. It is closely applied to the vagina and has a relationship with the neurovascular bundles (NVBs) that contain erectile fibers intended for the clitoris. The NVBs are situated anteriorly to the posterior extension of rectovaginal septum. This posterior extension protects the NVBs during the anterior and anterolateral dissection for removal of rectal cancer. CONCLUSIONS: To reduce the risk of postoperative sexual dysfunction in women undergoing TME for rectal cancer, we recommend careful dissection to the anterior mesorectum to develop a plane of dissection behind the posterior extension of the RVS if oncologically reasonable. PMID- 21976013 TI - NCCN Biosimilars White Paper: regulatory, scientific, and patient safety perspectives. AB - Biologics are essential to oncology care. As patents for older biologics begin to expire, the United States is developing an abbreviated regulatory process for the approval of similar biologics (biosimilars), which raises important considerations for the safe and appropriate incorporation of biosimilars into clinical practice for patients with cancer. The potential for biosimilars to reduce the cost of biologics, which are often high-cost components of oncology care, was the impetus behind the Biologics Price Competition and Innovation Act of 2009, a part of the 2010 Affordable Care Act. In March 2011, NCCN assembled a work group consisting of thought leaders from NCCN Member Institutions and other organizations, to provide guidance regarding the challenges health care providers and other key stakeholders face in incorporating biosimilars in health care practice. The work group identified challenges surrounding biosimilars, including health care provider knowledge, substitution practices, pharmacovigilance, naming and product tracking, coverage and reimbursement, use in off-label settings, and data requirements for approval. PMID- 21976014 TI - Expanding molecular transition metal cubane clusters of the form [M4(MU3) O)4]12+: syntheses, spectroscopic and structural characterizations of molecules M4(MU3-O)4(O2P(Bn)2)4(O4), M = V(V) and W(V). AB - Oxidizing the trimer V(3)(MU(3)-O)(O(2))(MU(2)-O(2)P(Bn)(2))(6)(H(2)O) in the presence of excess (t)BuOOH results in V(4)(MU(3)-O)(4)(MU(2) O(2)P(Bn)(2))(4)(O(4)) and heating W(CO)(6) and bis(benzyl)phosphinic acid in 1:1 EtOH/THF at 120 degrees C produces W(4)(MU(3)-O)(4)(MU(2) O(2)P(Bn)(2))(4)(O(4)). PMID- 21976015 TI - A low-fidelity simulator for nasendoscopy training. PMID- 21976016 TI - Robustness index score: a new stability parameter for designing robustness into biologic formulations. AB - Formulation robustness is critical to product quality. A challenge in designing robustness into biologic formulations is the absence of one global parameter, which allows equitable comparison across formulations and quality measures. The new measure introduced here derived from accelerated testing data allows for the design of globally optimal robust formulations. The measure is easy to understand and also numerically and computationally stable when performing optimizations. The measure termed here as robustness index (RobX) score is a relative measure allowing for global optimization across multiple critical quality attributes. Described here are the calculation methods, a discussion of the measure characteristics, and a brief example of using RobX to find a global optimal formulation across multiple quality characteristics within the framework of a mixture experimental design. The data presented are actual stability data generated during a formulation experimental design for a monoclonal antibody. We anticipate this approach will provide a good general measure of drug stability and will help to accelerate the drug development process. We believe it will improve formulation robustness, long-term stability, and the delivery of quality drug products to the patient. PMID- 21976017 TI - Rapid and sensitive colorimetric visualization of phthalates using UTP-modified gold nanoparticles cross-linked by copper(II). AB - A simple and reliable colorimetric method for determination of phthalates is developed utilizing uridine-5'-triphosphate (UTP)-modified gold nanoparticles as a color indicator and Cu(2+) as a cross-linker. The method demonstrates superior sensitivity with a detection limit of phthalates of ca. 0.5 ppm. PMID- 21976018 TI - Genetic and epigenetic effects of environmental arsenicals. AB - Environmental arsenic compounds and their methylated metabolites do not form adducts with DNA, but do cause oxidative DNA damage. Chromosome aberrations are seen at toxic concentrations. Genetic effects that occur at non-toxic concentrations include aneuploidy, comutagenesis (resulting from indirect effects on DNA repair), and delayed mutagenesis (probably secondary to aneuploidy and/or epigenetic effects). Effects of trivalent arsenicals on poly(ADP ribose) polymerase and P53 activation may mediate effects on DNA repair and aneuploidy. A growing literature points to the epigenetic effects of arsenic compounds in cells and in vivo. A review of the current literature on DNA methylation, histone modifications and microRNA effects is presented. PMID- 21976019 TI - Multifunctional amphiphilic carbonaceous microcapsules catalyze water/oil biphasic reactions. AB - Multifunctional amphiphilic hollow carbonaceous spheres assembled into Pickering emulsions exhibit reversible pH-dependent phase-transfer behavior and can efficiently catalyze water/oil biphasic reactions, facilitating the recycling of the catalysts and separation of the products. PMID- 21976020 TI - Metabolic priming by a secreted fungal effector. AB - Maize smut caused by the fungus Ustilago maydis is a widespread disease characterized by the development of large plant tumours. U. maydis is a biotrophic pathogen that requires living plant tissue for its development and establishes an intimate interaction zone between fungal hyphae and the plant plasma membrane. U. maydis actively suppresses plant defence responses by secreted protein effectors. Its effector repertoire comprises at least 386 genes mostly encoding proteins of unknown function and expressed exclusively during the biotrophic stage. The U. maydis secretome also contains about 150 proteins with probable roles in fungal nutrition, fungal cell wall modification and host penetration as well as proteins unlikely to act in the fungal-host interface like a chorismate mutase. Chorismate mutases are key enzymes of the shikimate pathway and catalyse the conversion of chorismate to prephenate, the precursor for tyrosine and phenylalanine synthesis. Root-knot nematodes inject a secreted chorismate mutase into plant cells likely to affect development. Here we show that the chorismate mutase Cmu1 secreted by U. maydis is a virulence factor. The enzyme is taken up by plant cells, can spread to neighbouring cells and changes the metabolic status of these cells through metabolic priming. Secreted chorismate mutases are found in many plant-associated microbes and might serve as general tools for host manipulation. PMID- 21976021 TI - Active tactile exploration using a brain-machine-brain interface. AB - Brain-machine interfaces use neuronal activity recorded from the brain to establish direct communication with external actuators, such as prosthetic arms. It is hoped that brain-machine interfaces can be used to restore the normal sensorimotor functions of the limbs, but so far they have lacked tactile sensation. Here we report the operation of a brain-machine-brain interface (BMBI) that both controls the exploratory reaching movements of an actuator and allows signalling of artificial tactile feedback through intracortical microstimulation (ICMS) of the primary somatosensory cortex. Monkeys performed an active exploration task in which an actuator (a computer cursor or a virtual-reality arm) was moved using a BMBI that derived motor commands from neuronal ensemble activity recorded in the primary motor cortex. ICMS feedback occurred whenever the actuator touched virtual objects. Temporal patterns of ICMS encoded the artificial tactile properties of each object. Neuronal recordings and ICMS epochs were temporally multiplexed to avoid interference. Two monkeys operated this BMBI to search for and distinguish one of three visually identical objects, using the virtual-reality arm to identify the unique artificial texture associated with each. These results suggest that clinical motor neuroprostheses might benefit from the addition of ICMS feedback to generate artificial somatic perceptions associated with mechanical, robotic or even virtual prostheses. PMID- 21976022 TI - Low-Mach-number turbulence in interstellar gas revealed by radio polarization gradients. AB - The interstellar medium of the Milky Way is multiphase, magnetized and turbulent. Turbulence in the interstellar medium produces a global cascade of random gas motions, spanning scales ranging from 100 parsecs to 1,000 kilometres (ref. 4). Fundamental parameters of interstellar turbulence such as the sonic Mach number (the speed of sound) have been difficult to determine, because observations have lacked the sensitivity and resolution to image the small-scale structure associated with turbulent motion. Observations of linear polarization and Faraday rotation in radio emission from the Milky Way have identified unusual polarized structures that often have no counterparts in the total radiation intensity or at other wavelengths, and whose physical significance has been unclear. Here we report that the gradient of the Stokes vector (Q, U), where Q and U are parameters describing the polarization state of radiation, provides an image of magnetized turbulence in diffuse, ionized gas, manifested as a complex filamentary web of discontinuities in gas density and magnetic field. Through comparison with simulations, we demonstrate that turbulence in the warm, ionized medium has a relatively low sonic Mach number, M(s) ? 2. The development of statistical tools for the analysis of polarization gradients will allow accurate determinations of the Mach number, Reynolds number and magnetic field strength in interstellar turbulence over a wide range of conditions. PMID- 21976024 TI - Ocean-like water in the Jupiter-family comet 103P/Hartley 2. AB - For decades, the source of Earth's volatiles, especially water with a deuterium to-hydrogen ratio (D/H) of (1.558 +/- 0.001) * 10(-4), has been a subject of debate. The similarity of Earth's bulk composition to that of meteorites known as enstatite chondrites suggests a dry proto-Earth with subsequent delivery of volatiles by local accretion or impacts of asteroids or comets. Previous measurements in six comets from the Oort cloud yielded a mean D/H ratio of (2.96 +/- 0.25) * 10(-4). The D/H value in carbonaceous chondrites, (1.4 +/- 0.1) * 10( 4), together with dynamical simulations, led to models in which asteroids were the main source of Earth's water, with <=10 per cent being delivered by comets. Here we report that the D/H ratio in the Jupiter-family comet 103P/Hartley 2, which originated in the Kuiper belt, is (1.61 +/- 0.24) * 10(-4). This result substantially expands the reservoir of Earth ocean-like water to include some comets, and is consistent with the emerging picture of a complex dynamical evolution of the early Solar System. PMID- 21976023 TI - An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. AB - Activation of the aryl hydrocarbon receptor (AHR) by environmental xenobiotic toxic chemicals, for instance 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin), has been implicated in a variety of cellular processes such as embryogenesis, transformation, tumorigenesis and inflammation. But the identity of an endogenous ligand activating the AHR under physiological conditions in the absence of environmental toxic chemicals is still unknown. Here we identify the tryptophan (Trp) catabolite kynurenine (Kyn) as an endogenous ligand of the human AHR that is constitutively generated by human tumour cells via tryptophan-2,3-dioxygenase (TDO), a liver- and neuron-derived Trp-degrading enzyme not yet implicated in cancer biology. TDO-derived Kyn suppresses antitumour immune responses and promotes tumour-cell survival and motility through the AHR in an autocrine/paracrine fashion. The TDO-AHR pathway is active in human brain tumours and is associated with malignant progression and poor survival. Because Kyn is produced during cancer progression and inflammation in the local microenvironment in amounts sufficient for activating the human AHR, these results provide evidence for a previously unidentified pathophysiological function of the AHR with profound implications for cancer and immune biology. PMID- 21976025 TI - Crystal structure of a bacterial homologue of the bile acid sodium symporter ASBT. AB - High cholesterol levels greatly increase the risk of cardiovascular disease. About 50 per cent of cholesterol is eliminated from the body by its conversion into bile acids. However, bile acids released from the bile duct are constantly recycled, being reabsorbed in the intestine by the apical sodium-dependent bile acid transporter (ASBT, also known as SLC10A2). It has been shown in animal models that plasma cholesterol levels are considerably lowered by specific inhibitors of ASBT, and ASBT is thus a target for hypercholesterolaemia drugs. Here we report the crystal structure of a bacterial homologue of ASBT from Neisseria meningitidis (ASBT(NM)) at 2.2 A. ASBT(NM) contains two inverted structural repeats of five transmembrane helices. A core domain of six helices harbours two sodium ions, and the remaining four helices pack in a row to form a flat, 'panel'-like domain. Overall, the architecture of the protein is remarkably similar to the sodium/proton antiporter NhaA, despite having no detectable sequence homology. The ASBT(NM) structure was captured with the substrate taurocholate present, bound between the core and panel domains in a large, inward facing, hydrophobic cavity. Residues near this cavity have been shown to affect the binding of specific inhibitors of human ASBT. The position of the taurocholate molecule, together with the molecular architecture, suggests the rudiments of a possible transport mechanism. PMID- 21976026 TI - Developmental changes of nasal and oral calls in the goitred gazelle Gazella subgutturosa, a nonhuman mammal with a sexually dimorphic and descended larynx. AB - In goitred gazelles (Gazella subgutturosa), sexual dimorphism of larynx size and position is reminiscent of the case in humans, suggesting shared features of vocal ontogenesis in both species. This study investigates the ontogeny of nasal and oral calls in 23 (10 male and 13 female) individually identified goitred gazelles from shortly after birth up to adolescence. The fundamental frequency (f0) and formants were measured as the acoustic correlates of the developing sexual dimorphism. Settings for LPC analysis of formants were based on anatomical dissections of 5 specimens. Along ontogenesis, compared to females, male f0 was consistently lower both in oral and nasal calls and male formants were lower in oral calls, whereas the first two formants of nasal calls did not differ between sexes. In goitred gazelles, significant sex differences in f0 and formants appeared as early as the second week of life, while in humans they emerge only before puberty. This result suggests different pathways of vocal ontogenesis in the goitred gazelles and in humans. PMID- 21976027 TI - Utilization of two web-based continuing education courses evaluated by Markov chain model. AB - OBJECTIVES: To evaluate the web structure of two web-based continuing education courses, identify problems and assess the effects of web site modifications. DESIGN: Markov chain models were built from 2008 web usage data to evaluate the courses' web structure and navigation patterns. The web site was then modified to resolve identified design issues and the improvement in user activity over the subsequent 12 months was quantitatively evaluated. MEASUREMENTS: Web navigation paths were collected between 2008 and 2010. The probability of navigating from one web page to another was analyzed. RESULTS: The continuing education courses' sequential structure design was clearly reflected in the resulting actual web usage models, and none of the skip transitions provided was heavily used. The web navigation patterns of the two different continuing education courses were similar. Two possible design flaws were identified and fixed in only one of the two courses. Over the following 12 months, the drop-out rate in the modified course significantly decreased from 41% to 35%, but remained unchanged in the unmodified course. The web improvement effects were further verified via a second order Markov chain model. CONCLUSIONS: The results imply that differences in web content have less impact than web structure design on how learners navigate through continuing education courses. Evaluation of user navigation can help identify web design flaws and guide modifications. This study showed that Markov chain models provide a valuable tool to evaluate web-based education courses. Both the results and techniques in this study would be very useful for public health education and research specialists. PMID- 21976029 TI - Fast detection of genetic information by an optimized PCR in an interchangeable chip. AB - In this paper, we report the construction of a polymerase chain reaction (PCR) device for fast amplification and detection of DNA. This device consists of an interchangeable PCR chamber, a temperature control component as well as an optical detection system. The DNA amplification happens on an interchangeable chip with the volumes as low as 1.25 MUl, while the heating and cooling rate was as fast as 12.7 degrees C/second ensuring that the total time needed of only 25 min to complete the 35 cycle PCR amplification. An optimized PCR with two temperature approach for denaturing and annealing (Td and Ta) of DNA was also formulated with the PCR chip, with which the amplification of male-specific sex determining region Y (SRY) gene marker by utilizing raw saliva was successfully achieved and the genetic identification was in-situ detected right after PCR by the optical detection system. PMID- 21976028 TI - Patient portal doldrums: does an exam room promotional video during an office visit increase patient portal registrations and portal use? AB - The patient portal is a web service which allows patients to view their electronic health record, communicate online with their care teams, and manage healthcare appointments and medications. Despite advantages of the patient portal, registrations for portal use have often been slow. Using a secure video system on our existing exam room electronic health record displays during regular office visits, the authors showed patients a video which promoted use of the patient portal. The authors compared portal registrations and portal use following the video to providing a paper instruction sheet and to a control (no additional portal promotion). From the 12,050 office appointments examined, portal registrations within 45 days of the appointment were 11.7%, 7.1%, and 2.5% for video, paper instructions, and control respectively (p<0.0001). Within 6 months following the interventions, 3.5% in the video cohort, 1.2% in the paper, and 0.75% of the control patients demonstrated portal use by initiating portal messages to their providers (p<0.0001). PMID- 21976030 TI - Tension-type headache mimics. PMID- 21976031 TI - Diagnosis of ADHD in adults: what is the appropriate DSM-5 symptom threshold for hyperactivity-impulsivity? AB - OBJECTIVE: To empirically identify the appropriate symptom threshold for hyperactivity-impulsivity for diagnosis of ADHD in adults. METHOD: Participants were 88 adults (M [SD] age = 41.69 [11.78] years, 66% female, 16% minority) meeting formal DSM-IV criteria for ADHD combined or predominantly inattentive subtypes based on a structured diagnostic interview keyed to DSM-IV (Conners' Adult ADHD Diagnostic Interview for DSM-IV [CAADID]). All participants also completed the Conners' Adult ADHD Rating Scale (CAARS), which was normed on the general adult population and includes subscales for DSM-IV inattentive and DSM-IV hyperactive-impulsive symptoms. A T-score threshold of 65 (at least 1.5 SD above population mean) on the CAARS DSM-IV hyperactive-impulsive dimension was used to identify participants with empirically elevated symptom severity. RESULTS: Of 88 participating adults, 48 (55%) had a T-score of at least 65 (1.5 SD) on the CAARS DSM-IV Hyperactive-Impulsive scale. Of these, only 25 (52%) met the DSM-IV cutoff of six hyperactive-impulsive symptoms on the CAADID. Thus, approximately half of those who reported empirically elevated hyperactive-impulsive complaints on the CAARS did not concurrently meet the six-symptom DSM-IV cutoff on the CAADID. An alternative cutoff of four hyperactive-impulsive symptoms on the CAADID captured 39 (81%) cases identified by the CAARS. CONCLUSION: In adults, mandating at least six hyperactive-impulsive symptoms excludes a significant percentage (almost half) of adults who are at least 1.5 SD above the population mean on a dimensional measure of hyperactivity-impulsivity. These data provide a compelling basis for lowering the symptom threshold of hyperactivity-impulsivity for adults in the DSM-5. PMID- 21976032 TI - Putting families in the center: family perspectives on decision making and ADHD and implications for ADHD care. AB - OBJECTIVE: To examine components of family-centered care in families' stories about treatment decision making for their child with ADHD. METHOD: Twenty-eight families participated in qualitative interviews that addressed families' perspectives on (a) the treatment decision-making process, (b) the cause and impact of their child's symptoms, and (c) treatment goals and preferences. RESULTS: The majority of families preferred to be primary or shared decision makers regarding treatment decisions. Families' perspectives on the cause of the child's symptoms varied and often were not consistent with a biomedical framework. Families described multiple areas of impairment on child, family relationships, and family functioning. Perspectives toward evidence-based treatments were mixed, with families also expressing interest in and pursuing interventions not delineated in current treatment guidelines. CONCLUSION: These findings reinforce the importance of eliciting families' perspectives and involving these important stakeholders in shared decision making as critical components of family-centered care for children with ADHD. PMID- 21976033 TI - ADHD and female specific concerns: a review of the literature and clinical implications. AB - ADHD was once thought of as a predominantly male disorder. While this may be true for ADHD in childhood, extant research suggests that the number of women with ADHD may be nearly equal to that of men with the disorder (Faraone et al., 2000). There is accumulating research which clearly indicates subtle but important sex differences exist in the symptom profile, neuropathology and clinical course of ADHD. Compared to males with ADHD, females with ADHD are more prone to have difficulties with inattentive symptoms than hyperactive and impulsive symptoms, and females often receive a diagnosis of ADHD significantly later than do males (Gaub & Carlson, 1997; Gershon, 2002a, 2002b). Emerging evidence suggests differences exist in the neuropathology of ADHD, and there are hormonal factors which may play an important role in understanding ADHD in females. Although research demonstrates females with ADHD differ from males in important ways, little research exists that evaluates differences in treatment response. Given the subtle but important differences in presentation and developmental course of ADHD, it is essential that both clinical practice and research be informed by awareness of these differences in order to better identify and promote improved quality of care to girls and women with ADHD. PMID- 21976034 TI - Possible logistic and sociodemographyc factors on breast cancer screening in Turkey: lessons from a women's health project in Mersin province. AB - Mortality from breast cancer is decreasing partly owing to early detection. In Mersin province in our country, local health authorities launched an education program on sexual diseases and breast cancer early detection for women over 15 years of age. After the educational session, clinical breast examination was offered by a nurse or physician, and if suspicious they were recommended to apply a specialist for further examination. Here, we report the results on those women with abnormal clinical breast examination. In this second project, socio demographic variables were investigated such as educational level and place of living,parameters to measure the success of previous project, whether they followed the recommendation themselves, whether mammograms were reported in accordance with Breast Imaging Reporting and Data System (BIRADS). Of 3,793 women recruited, mean age was 42.2 years, 42.3%were younger than 40.0 years. Majority (88.5%) were married, graduate of primary school (60.6%), without a job(91.2%), and inhabiting in the province (38.7%). Of the population, 98.1% believe in the importance of screening in the treatment of breast cancer. According to 70.3%,monthly breast self-examination enables early detection, 33.5% believe that clinical breast examination detects cancer early, and 35.5% think that annual mammography can detect it early. Among 2,183 women 40 years of age or over, 41.5% had mammography at once before participating in the first project. Breast self examination was being carried out by 56.6% on a monthly basis. After an abnormal breast examination, 86.4% applied to hospitals for specialist examination. Reasons for declining to seek for further examination among 410 women answering were as follows:42.0% did not accept, 27.0% did not know it was important, 16.6% because of economical reasons, and 5.0% were too shy to be examined. Being older, being married, being the graduate of primary and secondary school, residing in rural areas, having a mammogram positively affected the decision in univariate analyses (p<0.05). All but educational level (p=0.059) remained significant in multivariate analysis. Mammography was reported in accordance with BIRADS in only 45 (1.2%). Awareness of population on breast cancer early detection can be raised through education. Generally, women follow professional recommendation from professionals. Mammography reporting among radiologist in accordance with BIRADS is rare. Successful early detection of breast cancer may be obtained by public education together with improving detection methods. PMID- 21976036 TI - Validation of the Brazilian Portuguese version of the Medical Outcomes Study Social Support Survey in Hodgkin's lymphoma survivors. AB - PURPOSE: The aim of this study was to assess the psychometric properties of the Brazilian Portuguese version of the "Medical Outcomes Study-Social Support Survey (MOS-SSS)" in Hodgkin's lymphoma (HL) survivors. METHODS: The MOS-SSS is a 19 item questionnaire with five scales covering different aspects of social support (affection, positive social interaction, emotional, informational, and material). A sample of 200 HL survivors completed a self-administered questionnaire at the treatment center or at home. RESULTS: The median age of the patients at diagnosis was 29 years (16-77), and the median follow-up since diagnosis was 7 years (3.6 12.7). Item-corrected Pearson correlation coefficients between items and their dimensions varied from 0.57 to 0.76. Internal consistency, evaluated using Cronbach's alpha, was 0.95 for the overall scale, ranging from 0.78 to 0.87 for the five subscales proposed by the original instrument. An exploratory factor analysis yielded a three-factor solution, aggregating affection and positive social interaction, and emotional and informational dimensions of social support. Higher socioeconomic status and higher social network were associated with higher levels of all kinds of support. CONCLUSION: Results show good general psychometric properties of the Brazilian version of the MOS-SSS when applied to HL survivors. The three-factor structure identified in this study is in line with a previous validation among Brazilian healthy civil servants. The Brazilian Portuguese version will now be used to evaluate social support and its association with long-term disease outcomes and quality of life of Hodgkin's lymphoma survivors. PMID- 21976035 TI - Incidence of delayed nausea and vomiting in patients with colorectal cancer receiving irinotecan-based chemotherapy. AB - PURPOSE: This study sought to prospectively determine the frequency of delayed nausea and vomiting with irinotecan-based chemotherapy following day 1 prophylaxis with a 5-HT3 receptor antagonist and dexamethasone. METHODS: Patients with colorectal cancer aged >= 18 years with ECOG performance status <= 2 receiving irinotecan alone, combined with cetuximab or as part of a standard folinic acid, 5- fluorouracil, irinotecan (FOLFIRI) regimen for the first time were eligible. All patients received a 5-HT3 receptor antagonist and dexamethasone 8 mg on day 1 prior to irinotecan. No routine prophylaxis for delayed emesis was given. Antiemetic outcome was recorded in patient-completed diaries for the 120-h study period after irinotecan administration. Primary endpoint was frequency of delayed (24-120 h) emesis. RESULTS: Forty-four patients were enrolled, and all are evaluable. The median age was 61 (39-79) years; the male-female ratio was 37:7. Four patients (9%) experienced vomiting or retching during the delayed period. Three patients (7%) vomited during the first 24 h after irinotecan. The overall no emesis rate was 89% (39/44). Fifteen patients (34%) experienced delayed nausea (mildin 11 patients, moderate in four patients). Six patients (14%) took rescue antiemetics during the delayed period. Delayed and overall complete response (no emesis or use of rescue antiemetics) rates were 82% and 77% respectively. CONCLUSIONS: The use of a 5-HT3 antagonist and dexamethasone prior to irinotecan results in excellent control of nausea and vomiting (CR 86%) during the 24 h after chemotherapy. Without further antiemetic treatment, most patients (82%) will not experience delayed emesis or require rescue antiemetics. Routine prophylaxis for delayed emesis following irinotecan does not appear to be warranted. PMID- 21976038 TI - Syntheses, reactions, and ethylene polymerization of half-sandwich titanium complexes containing salicylbenzoxazole and salicylbenzothiazole ligands. AB - Half-sandwich titanium salicylbenzoxazole complexes CpTiLCl(2) 2a-2c [L = R-2 (benzo[d]xazol-2-yl)phenol (R = H (2a), R = 6-CH(3) (2b), R = 4-CH(3)-6-(t)Bu (2c)] and salicylbenzothiazole complexes CpTiLCl(2) 2d-2g [L = R-2 (benzo[d]thiazol-2-yl)phenol (R = H (2d), R = 6-CH(3) (2e), R = 6-(t)Bu (2f), R = 4-Cl (2g)] were synthesized by the reaction of CpTiCl(3) with the sodium salts of their corresponding precursors. Complexes 2a-2g were fully characterized by (1)H and (13)C NMR spectra and elemental analyses. The molecular structures of 2a and 2b were determined by single crystal X-ray diffraction methods. When activated by excess methylaluminoxane (MAO) these half-sandwich titanium complexes showed moderate to high activities for ethylene polymerization and produced high molecular weight polyethylenes. The half-sandwich titanium salicylbenzoxazole complexes (2a-2c) exhibited higher activities, of up to 1.23 * 10(6) g PE mol Ti( 1) h(-1) for the 2b/MAO system, than those of their analogues, half-sandwich titanium salicylbenzothiazole complexes (2d-2g). PMID- 21976039 TI - Radiofrequency guide wire recanalization of venous occlusions in patients with malignant superior vena cava syndrome. AB - Fibrotic central venous occlusions in patients with thoracic malignancy and prior radiotherapy can be impassable with standard catheters and wires, including the trailing or stiff end of a hydrophilic wire. We report two patients with superior vena cava syndrome in whom we successfully utilized a radiofrequency guide wire (PowerWire, Baylis Medical, Montreal, Quebec, Canada) to perforate through the occlusion and recanalize the occluded segment to alleviate symptoms. PMID- 21976040 TI - Pro-inflammatory cytokines induce odontogenic differentiation of dental pulp derived stem cells. AB - Postnatal dental pulp stem cells (DPSCs) represent a unique precursor population in the dental pulp, which have multipotential and harbor great potential for tissue engineering purposes. However, for therapy applications, transplanted cells are often exposed to unfavorable conditions such as cytokines released from necrotic or inflammatory cells in injured tissues. It is not clear how stem cells exposed to these conditions changes in their characteristics. In this study, the effects of pro-inflammatory cytokines, such as IL-1 and TNF, on DPSCs were investigated. Cells were treated with IL-1, TNF, or both for 3, 7, and 12 days. The cultures were evaluated for cell proliferation, ALP activity, and real-time PCR. We found that a short treatment (3 days) of pro-inflammatory cytokines induced the odontogenic differentiation of DPSCs. Furthermore, post 3 days treatment with pro-inflammatory cytokines, the cell-scaffold complexes were implanted subcutaneously in mice for 8 weeks. Histological analysis demonstrated that the cultures gave obviously mineralized tissue formation, especially for both IL-1 and TNF applied. These data suggest that IL-1 and TNF produced in the early inflammatory reaction may induce the mineralization of DPSCs. PMID- 21976041 TI - [Diagnose importance of multiparametric magnetic resonance tomography for prostate cancer]. AB - Prostate cancer is biologically and clinically a heterogeneous disease which makes imaging evaluation challenging. Magnetic resonance imaging (MRI) has considerable potential to improve prostate cancer detection and characterization. Until recently morphologic MRI has not been routinely incorporated into clinical care because of its limitation to detect, localize and characterize prostate cancer. Performing prostate gland MRI using functional techniques has the potential to provide unique information regarding tumor behavior, including treatment response. In order for multiparametric MRI data to have an impact on patient management, the collected data need to be relayed to clinicians in a standardized way for image construction, analysis and interpretation. This will ensure that patients are treated effectively and in the most appropriate way. Scoring systems similar to those employed successfully for breast imaging need to be developed. PMID- 21976042 TI - Opposite effects of amphetamine on impulsive action with fixed and variable delays to respond. AB - Impulsive action, the failure to withhold an inappropriate response, is treated clinically with dopamine agonists such as amphetamine. Despite the therapeutic efficacy, these drugs have inconsistent effects on impulsive action in rodents, causing improvements or disruptions in different tasks. Thus, we hypothesized that amphetamine is producing an effect by altering distinct cognitive processes in each task. To test this idea, we used the response inhibition (RI) task and trained rats to withhold responding for sucrose until a signal is presented. We then varied the duration that subjects were required to inhibit responding (short=4 s; long=60 s; or variable=1-60 s) and examined whether this influenced the pattern of premature responses. We also tested the effects of amphetamine (0.0, 0.125, 0.25, 0.5, and 1.0 mg/kg) on each task variant. The probability of premature responding varied across the premature interval with a unique pattern of time-dependent errors emerging in each condition. Amphetamine also had distinct effects on each version: the drug promoted premature responding when subjects expected a consistent delay, regardless of its duration, but reduced premature responding when the delay was unpredictable. We propose that the ability to inhibit a motor response is controlled by a different combination of cognitive processes in the three task conditions. These include timing, conditioned avoidance, and attention, which then interact with amphetamine to increase or decrease impulsive action. The effect of amphetamine on impulsive action, therefore, is not universal, but depends on the subject's experience and expectation of the task demands. PMID- 21976043 TI - Somatic treatments for mood disorders. AB - Somatic treatments for mood disorders represent a class of interventions available either as a stand-alone option, or in combination with psychopharmacology and/or psychotherapy. Here, we review the currently available techniques, including those already in clinical use and those still under research. Techniques are grouped into the following categories: (1) seizure therapies, including electroconvulsive therapy and magnetic seizure therapy, (2) noninvasive techniques, including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and cranial electric stimulation, (3) surgical approaches, including vagus nerve stimulation, epidural electrical stimulation, and deep brain stimulation, and (4) technologies on the horizon. Additionally, we discuss novel approaches to the optimization of each treatment, and new techniques that are under active investigation. PMID- 21976047 TI - Significant proteins affecting cerebral vasospasm using complementary ICPMS and MALDI-MS. AB - Cerebral vasospasm (CV) following subarachnoid hemorrhagic stroke affects more than one million people each year. The etiology and prevention of CV is currently of great interest to researchers in various fields of medical science. More recently, the idea that selenium could be playing a major role in the onset of cerebral vasospasm has come into the spotlight. This study focused on using newly established metallomics techniques in order to explore the proteome associated with CV and if selenium might affect the discovered proteins. Size exclusion chromatography coupled to inductively coupled plasma mass spectrometry, along with LC-MALDI-TOF/TOF were both essential in determining protein identifications in three different sample types; a control (normal, healthy patient, CSF control), SAH stroke patients (no vasospasm, CSF C) and SAH CV patients (CSF V). The results of this study, although preliminary, indicate the current methods are applicable and warrant further application to these clinically important targets. PMID- 21976045 TI - Reversal of dopamine inhibition of dopaminergic neurons of the ventral tegmental area is mediated by protein kinase C. AB - Adaptation of putative dopaminergic (pDA) neurons in the ventral tegmental area (VTA) to drugs of abuse may alter information processing related to reward and reinforcement and is an important factor in the development of addiction. We have demonstrated that prolonged increases in the concentration of dopamine (DA) result in a time-dependent decrease in sensitivity of pDA neurons to DA, which we termed DA inhibition reversal (DIR). In this study, we used extracellular recordings to examine factors mediating DIR. A 40 min administration of DA (2.5 10 MUM), but not the DA D2 receptor agonist quinpirole (50-200 nM), resulted in inhibition of neuronal firing followed by DIR. In the presence of 100 nM cocaine, inhibition followed by DIR was seen with much lower DA concentrations. Reversal of quinpirole inhibition could be induced by an activator of protein kinase C, but not of protein kinase A. Inhibitors of protein kinase C or phospholipase C blocked the development of DIR. Disruption of intracellular calcium release also prevented DIR. Reduction of extracellular calcium or inhibition of store-operated calcium entry blocked DIR, but the L-type calcium channel blocker nifedipine did not. DIR was age-dependent and not seen in pDA VTA neurons from rat pups younger than 15 days postnatally. Our data indicate that DIR is mediated by protein kinase C, and implicate a conventional protein kinase C. This characterization of DIR gives insight into the regulation of autoinhibition of pDA VTA neurons, and the resulting long-term alteration in information processing related to reward and reinforcement. PMID- 21976048 TI - Application of mesoporous silicon dioxide and silicate in oral amorphous drug delivery systems. AB - Aqueous solubility of an active pharmaceutical ingredient is an important consideration to ensure successful drug development. Mesoporous materials have been investigated as an amorphous drug delivery system owing to their nanosized capillaries and large surface areas. The complex interactions of crystalline compounds with mesoporous media and their implication in drug delivery are not well understood. Molecules interacting with porous media behave very differently than those in bulk phase. Their altered dynamics and thermodynamics play an important role in the properties and product performance of the amorphous system. In this review, application of mesoporous silicon dioxide and silicates in drug amorphization is the main focus. First, as background, the nature of gas-porous media interactions is summarized. The synthesis of various types of mesoporous silica, which are used by many investigators in this field, is described. Second, the behavior of molecules confined in mesopores is compared with those in bulk, crystalline phase. The molecular dynamics of compounds due to confinement, analyzed using various techniques, and their consequences in drug delivery are discussed. Finally, the preparation and performance of drug delivery systems using mesoporous silica are examined. PMID- 21976046 TI - The neuropeptide Y (NPY)-ergic system is associated with behavioral resilience to stress exposure in an animal model of post-traumatic stress disorder. AB - Converging evidence implicates the regulatory neuropeptide Y (NPY) in anxiety- and depression-related behaviors. The present study sought to assess whether there is an association between the magnitude of behavioral responses to stress and patterns of NPY in selected brain areas, and subsequently, whether pharmacological manipulations of NPY levels affect behavior in an animal model of PTSD. Animals were exposed to predator-scent stress for 15 min. Behaviors were assessed with the elevated plus maze and acoustic startle response tests 7 days later. Preset cutoff criteria classified exposed animals according to their individual behavioral responses. NPY protein levels were assessed in specific brain regions 8 days after the exposure. The behavioral effects of NPY agonist, NPY-Y1-receptor antagonist, or placebo administered centrally 1 h post-exposure were evaluated in the same manner. Immunohistochemical technique was used to detect the expression of the NPY, NPY-Y1 receptor, brain-derived neurotrophic factor, and GR 1 day after the behavioral tests. Animals whose behavior was extremely disrupted (EBR) selectively displayed significant downregulation of NPY in the hippocampus, periaqueductal gray, and amygdala, compared with animals whose behavior was minimally (MBR) or partially (PBR) disrupted, and with unexposed controls. One-hour post-exposure treatment with NPY significantly reduced prevalence rates of EBR and reduced trauma-cue freezing responses, compared with vehicle controls. The distinctive pattern of NPY downregulation that correlated with EBR as well as the resounding behavioral effects of pharmacological manipulation of NPY indicates an intimate association between NPY and behavioral responses to stress, and potentially between molecular and psychopathological processes, which underlie the observed changes in behavior. The protective qualities attributed to NPY are supported by the extreme reduction of its expression in animals severely affected by the stressor and imply a role in promoting resilience and/or recovery. PMID- 21976049 TI - Fluorescent 'two-faced' polymer wafers with embedded pyrene-functionalised gelator nanofibres. AB - Pyrene-functionalised gelators self-assemble into nano-fibrillar organogels in DMSO/styrene/divinylbenzene mixtures, which when polymerised yield polymer wafers with two distinct faces, only one of which is fluorescent and has embedded gelator nanofibres. PMID- 21976044 TI - Cognitive mechanisms of treatment in depression. AB - Cognitive abnormalities are a core feature of depression, and biases toward negatively toned emotional information are common, but are they a cause or a consequence of depressive symptoms? Here, we propose a 'cognitive neuropsychological' model of depression, suggesting that negative information processing biases have a central causal role in the development of symptoms of depression, and that treatments exert their beneficial effects by abolishing these biases. We review the evidence pertaining to this model: briefly with respect to currently depressed patients, and in more detail with respect to individuals at risk for depression and the effects of antidepressant treatments. As well as being present in currently depressed individuals, negative biases are detectable in those vulnerable for depression due to neuroticism, genetic risk, or previous depressive illness. Recent evidence provides strong support for the notion that both antidepressant drugs and psychological therapies modify negative biases, providing a common mechanism for understanding treatments for depression. Intriguingly, it may even be possible to predict which patients will benefit most from which treatments on the basis of neural responses to negative stimuli. However, further research is required to ascertain whether negative processing biases will be useful in predicting, detecting, and treating depression, and hence in preventing a chronic, relapsing course of illness. PMID- 21976050 TI - Some questions about two different surgical approaches of laminoplasty. PMID- 21976052 TI - The potential of smoking cessation programmes and a smoking ban in public places: comparing gain in life expectancy and cost effectiveness. AB - BACKGROUND: Interventions aimed at reducing the number of smokers are generally believed to be cost effective. However as the cost of the interventions should be paid up front whereas the gains in life years only appear in the future--the budgetary consequences might be a barrier to implementing such interventions. AIMS: The aim of the present paper was to assess the long-term cost effectiveness as well as the short-term (10 years) budget consequences of cessation programmes and a smoking ban in enclosed public places. METHODS: We develop a population based Markov model capable of analyzing both interventions and assess long-term costs effectiveness as well as short-term budgetary consequences and outcome gains. The smoking cessation programme model was based on data from the Danish National Smoking Cessation Database (SCDB), while the model of the smoking ban was based on effect estimates found in the literature. RESULTS: On a population level the effect of a smoking ban has the largest potential compared with the effect of smoking cessation programmes. Our results suggest that smoking cessation programmes are cost saving and generate life-years, whereas the costs per life-year gained by a smoking ban are 40,645 to 64,462 DKK (100 DKK = ?13.4). These results are conservative as they do not include the healthcare cost saving related to reduced passive smoking. CONCLUSIONS: Our results indicate that smoking cessation programmes and a smoking ban in enclosed public places both in the short term and the long term are cost-effective strategies compared with the status quo. PMID- 21976053 TI - Intake of whole grain in Scandinavia: intake, sources and compliance with new national recommendations. AB - AIMS: The aim of the present study was to describe the intake of whole grain (WG) in Norway, Sweden and Denmark, and to investigate what proportion of the study population that met the new WG recommendation (75 g WG/day per 10 MJ). METHODS: Descriptive study. Data is from one 24h dietary recall (24HDR) collected in 1995 2000 from a subset (n = 8,702) of the large Scandinavian cohort "HELGA" consisting of participants aged 30-65 years from three cohorts. RESULTS: The mean WG intake was far below the recommended level. Between 16% (Danish men) and 35% (Norwegian women) consumed at least the recommended intake of WG. Among women, the median intake of WG products (g WG products/day) was 114 g/day in Norway and 108 g/day in Denmark, whereas the intake was much lower in Sweden (64 g/day). For women, the median intake of WG in absolute amounts (g WG/day) was again highest in Norway (44 g/day), but lower in both Sweden (35 g/day) and Denmark (31 g/day). For men (no data available for Norwegian men), the intake of WG products was higher in Denmark (138 g/day) compared to Sweden (79 g/day), but when looking at the WG intake in absolute amounts, the intake was highest in Sweden (49 g/day) compared to Denmark (41 g/day). CONCLUSIONS: The present study described the intake of WG as well as the sources of WG in Norway, Sweden and Denmark. Between 16% and 35% met the new recommendations on intake of WG. PMID- 21976054 TI - Socioeconomic differences in outpatient healthcare utilisation are mainly seen for musculoskeletal problems in groups with poor self-rated health. AB - AIM: To assess whether there are socioeconomic (SES) differences in outpatient visits within groups of comparable morbidity (medical disease and self-rated health) and whether psychosocial factors can explain these differences. METHODS: Baseline data for SES, presence of disease, self-rated health (SRH), and psychosocial factors were collected during 2003-04 from 923 men and women aged 45 69 years in southeast Sweden. Outcome data were all registered outpatient healthcare visits to physicians during 2004-08. Cumulative incidences and standardised rate ratios (SSR) were calculated for strata of comparable morbidity for all visits, for visits due to cardiovascular disorders (CVD)/diabetes and for musculoskeletal problems. RESULTS: Low SES was associated with more outpatient visits due to musculoskeletal problems (SRR for education 1.52, 95% CI 1.35-1.73; for occupation 1.40, 95% CI 1.26-1.56) and accentuated in groups with poor SRH. The SES effect was significant for visits to primary care and to hospitals, for men and women, and independent of present disease, SRH, and psychosocial factors. Low SES was significantly associated with more total outpatient visits at primary healthcare centres. In contrast, for outpatient visits due to CVD/diabetes, high SES was related to more visits to hospitals among people with good SRH at baseline. CONCLUSIONS: We found a consistent pattern for outpatient visits related to musculoskeletal problems where people with low SES counted more visits and this was most prominent in groups of poor SRH. The results demonstrate the need to apply different morbidity measures when studying inequalities in healthcare utilisation. PMID- 21976056 TI - Compliance and persistence of endocrine adjuvant breast cancer therapy. AB - This study evaluates compliance and persistence in adjuvant endocrine breast cancer (BC) therapy by clearly analyzing reasons of therapy cessation by differentiating clinical meaningful situations. In order to illuminate the complex field of personal motivation to therapy, a single institution study with a more individual-based approach might better be suited to provide a detailed case documentation than the more epidemiologic approach of large database studies. An unselected cohort of 698 patients (<= 80 years) diagnosed with hormonal receptor-positive BC from 1997 to 2008 at the University Hospital Basel, Switzerland, was analyzed. The term "non-persistence" was exclusively used for patients where the discontinuation of endocrine therapy (ET) could have been modified by more intensive care and improved counseling (e.g., in women who lost faith/motivation to therapy or those who suffered from therapy-related side effects). These cases must be differentiated from cases where therapy cessation was inevitable (e.g., due to recurrent disease or severe intercurrent illness). Out of the 685 patients to whom ET was recommended, 42 patients (6.1%) refused and never began treatment (non-compliance). Women younger than 50 were more likely to be non-compliant (P < 0.001). 12.9% of the patients who started therapy were non-persistent to therapy. Patients who were treated by general practitioners tended to be non-persistent more often compared to those treated by oncologists (17.7% vs. 11.3%; P = 0.07). The aim of a non-persistence rate between 10 and 15% is realistic when patients are treated by specialized oncologists. Interventions are needed to support patients, particularly the younger ones, to comply with therapy. Efforts should be made to make sure that all physicians, above all general practitioners, who are involved in BC treatment, are provided with current knowledge as to guarantee an optimal patient management. PMID- 21976055 TI - Dose-dense doxorubicin and cyclophosphamide followed by dose-dense albumin-bound paclitaxel plus bevacizumab is safe as adjuvant therapy in patients with early stage breast cancer. AB - Every-2-week (dose-dense) adjuvant doxorubicin (A) plus cyclophosphamide (C) followed by cremophor-formulated paclitaxel (cf-P) was efficacious in metastatic breast cancer (BC). Albumin-bound paclitaxel (ab-P) was safe and more effective than cf-P, and the addition of bevacizumab to cf-P improved efficacy. This study compared the safety of dose-dense ab-P vs cf-P plus bevacizumab following dose dense adjuvant AC for early-stage BC. PATIENTS AND METHODS: Women with operable, histologically confirmed BC were randomized to 4 cycles of dose-dense A 60 mg/m(2) plus C 600 mg/m(2) IV with SC pegfilgrastim, followed by 4 cycles of either dose-dense IV ab-P 260 mg/m(2) or cf-P 175 mg/m(2). Bevacizumab was given during and following chemotherapy. 97 and 96% of patients completed 4 cycles of AC therapy, while 84 and 85% of patients completed 4 cycles of taxane therapy in the ab-P and cf-P arms, respectively (N = 197). Baseline patient characteristics were similar. The most common grade >=3 taxane-related adverse events (AEs) were fatigue and neutropenia. Dose reductions were similar between the treatment arms. During AC therapy, the majority of dose reductions were due to febrile neutropenia; during taxane therapy, the majority of cases were due to neuropathy. No taxane-related dose interruption occurred in the ab-P arm, while 3 occurred in the cf-P arm due to hypersensitivity reactions. The mean cumulative paclitaxel dose was 950.5 and 660.8 mg/m(2) in the ab-P and cf-P arms, respectively. A 44% higher paclitaxel dose was delivered in the ab-P compared with the cf-P arm (P < 0.0001), while achieving a similar safety profile. ab-P plus bevacizumab following AC therapy without prophylactic premedications was tolerable in early stage BC patients. PMID- 21976057 TI - Ageing in worms: N-acylethanolamines take control. PMID- 21976059 TI - A successful international cooperation with a bumpy start. PMID- 21976058 TI - Biotin biosynthesis in Mycobacterium tuberculosis: physiology, biochemistry and molecular intervention. AB - Biotin is an important micronutrient that serves as an essential enzyme cofactor. Bacteria obtain biotin either through de novo synthesis or by active uptake from exogenous sources. Mycobacteria are unusual amongst bacteria in that their primary source of biotin is through de novo synthesis. Here we review the importance of biotin biosynthesis in the lifecycle of Mycobacteria. Genetic screens designed to identify key metabolic processes have highlighted a role for the biotin biosynthesis in bacilli growth, infection and survival during the latency phase. These studies help to establish the biotin biosynthetic pathway as a potential drug target for new anti-tuberculosis agents. PMID- 21976060 TI - CUEDC2: an emerging key player in inflammation and tumorigenesis. AB - CUE domain-containing 2 (CUEDC2) is a protein involved in the regulation of the cell cycle, inflammation, and tumorigenesis and is highly expressed in many types of tumors. CUEDC2 is phosphorylated by Cdk1 during mitosis and promotes the release of anaphase-promoting complex or cyclosome (APC/C) from checkpoint inhibition. CUEDC2 is also known to interact with IkB kinase alpha (IKKalpha) and IKKbeta and has an inhibitory role in the activation of transcription factor nuclear factor-kappaB. Moreover, CUEDC2 plays an important role in downregulating the expression of hormone receptors estrogen receptor-alpha and progesterone receptor, thereby impairing the responsiveness of breast cancer to endocrine therapies. In this review, current knowledge on the multi-functions of CUEDC2 in normal processes and tumorigenesis are discussed and summarized. PMID- 21976061 TI - Pseudouridines in spliceosomal snRNAs. AB - Spliceosomal RNAs are a family of small nuclear RNAs (snRNAs) that are essential for pre-mRNA splicing. All vertebrate spliceosomal snRNAs are extensively pseudouridylated after transcription. Pseudouridines in spliceosomal snRNAs are generally clustered in regions that are functionally important during splicing. Many of these modified nucleotides are conserved across species lines. Recent studies have demonstrated that spliceosomal snRNA pseudouridylation is catalyzed by two different mechanisms: an RNA-dependent mechanism and an RNA-independent mechanism. The functions of the pseudouridines in spliceosomal snRNAs (U2 snRNA in particular) have also been extensively studied. Experimental data indicate that virtually all pseudouridines in U2 snRNA are functionally important. Besides the currently known pseudouridines (constitutive modifications), recent work has also indicated that pseudouridylation can be induced at novel positions under stress conditions, thus strongly suggesting that pseudouridylation is also a regulatory modification. PMID- 21976063 TI - Elevated levels of serum antibodies against alpha-1, 6-glucan in patients with systemic lupus erythematosus or rheumatoid arthritis. AB - This study was undertaken to investigate whether levels of anti-alpha-1, 6-glucan antibodies in human sera correlate with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Serum samples were collected from patients with SLE (n = 30), RA (n = 30) and healthy adult volunteers. IgG, IgA and IgM levels against alpha-1, 6-glucan were measured using enzyme linked immunosorbent assays. Anti alpha-1, 6-glucan IgG prevalence was raised in patients with active SLE (73.3%) and RA (60%) compared with healthy controls (13.3%). Strong correlation between anti-alpha-1,6-glucan-IgG levels and anti-perinuclear factor (r = 0.642; p < 0.05) in RA patients or anti-nuclear antibodies (r = 0.675; p < 0.05) in SLE patients was observed. No significant differences in anti-alpha-1,6-glucan-IgA or IgM levels were noted between different groups. We conclude that anti-alpha-1,6 glucan-IgG levels were significantly elevated in patients with SLE or RA and positively correlated with disease activity. PMID- 21976064 TI - Structural view of the regulatory subunit of aspartate kinase from Mycobacterium tuberculosis. AB - The aspartate kinase (AK) from Mycobacterium tuberculosis (Mtb) catalyzes the biosynthesis of aspartate family amino acids, including lysine, threonine, isoleucine and methionine. We determined the crystal structures of the regulatory subunit of aspartate kinase from Mtb alone (referred to as MtbAKbeta) and in complex with threonine (referred to as MtbAKbeta-Thr) at resolutions of 2.6 A and 2.0 A, respectively. MtbAKbeta is composed of two perpendicular non-equivalent ACT domains [aspartate kinase, chorismate mutase, and TyrA (prephenate dehydrogenase)] per monomer. Each ACT domain contains two alpha helices and four antiparallel beta strands. The structure of MtbAKbeta shares high similarity with the regulatory subunit of the aspartate kinase from Corynebacterium glutamicum (referred to as CgAKbeta), suggesting similar regulatory mechanisms. Biochemical assays in our study showed that MtbAK is inhibited by threonine. Based on crystal structure analysis, we discuss the regulatory mechanism of MtbAK. PMID- 21976062 TI - Molecular regulation of telomerase activity in aging. AB - The process of aging is mitigated by the maintenance and repair of chromosome ends (telomeres), resulting in extended lifespan. This review examines the molecular mechanisms underlying the actions and regulation of the enzyme telomerase reverse transcriptase (TERT), which functions as the primary mechanism of telomere maintenance and regulates cellular life expectancy. Underpinning increased cell proliferation, telomerase is also a key factor in facilitating cancer cell immortalization. The review focuses on aspects of hormonal regulations of telomerase, and the intracellular pathways that converge to regulate telomerase activity with an emphasis on molecular interactions at protein and gene levels. In addition, the basic structure and function of two key telomerase enzyme components-the catalytic subunit TERT and the template RNA (TERC) are discussed briefly. PMID- 21976065 TI - The role of the CNOT1 subunit of the CCR4-NOT complex in mRNA deadenylation and cell viability. AB - The human CCR4-NOT deadenylase complex consists of at least nine enzymatic and non-enzymatic subunits. Accumulating evidence suggests that the non-enzymatic subunits are involved in the regulation of mRNA deadenylation, although their precise roles remain to be established. In this study, we addressed the function of the CNOT1 subunit by depleting its expression in HeLa cells. Flow cytometric analysis revealed that the sub G(1) fraction was increased in CNOT1-depleted cells. Virtually, the same level of the sub G1 fraction was seen when cells were treated with a mixture of siRNAs targeted against all enzymatic subunits, suggesting that CNOT1 depletion induces apoptosis by destroying the CCR4-NOT associated deadenylase activity. Further analysis revealed that CNOT1 depletion leads to a reduction in the amount of other CCR4-NOT subunits. Importantly, the specific activity of the CNOT6L immunoprecipitates-associated deadenylase from CNOT1-depleted cells was less than that from control cells. The formation of P bodies, where mRNA decay is reported to take place, was largely suppressed in CNOT1-depleted cells. Therefore, CNOT1 has an important role in exhibiting enzymatic activity of the CCR4-NOT complex, and thus is critical in control of mRNA deadenylation and mRNA decay. We further showed that CNOT1 depletion enhanced CHOP mRNA levels and activated caspase-4, which is associated with endoplasmic reticulum ER stress-induced apoptosis. Taken together, CNOT1 depletion structurally and functionally deteriorates the CCR4-NOTcomplex and induces stabilization of mRNAs, which results in the increment of translation causing ER stress-mediated apoptosis. We conclude that CNOT1 contributes to cell viability by securing the activity of the CCR4-NOT deadenylase. PMID- 21976067 TI - Serendipity strikes again: scopolamine as an antidepressant agent in bipolar depressed patients. AB - The adrenergic-cholinergic balance hypothesis of mania and depression suggests that depression may be due to an over-activity or a hypersensitivity to central acetylcholine. From this hypothesis, it is logical that scopolamine, a centrally acting antimuscarinic agent, would be useful as an antidepressant. Authors, working at the Intramural Program at NIMH in Bethesda Maryland have shown that intravenous scopolamine is a rapidly acting, effective antidepressant and have than replicated this finding. They now report that this antidepressant effect occurs in bipolar, as well as unipolar depressed patients. The clinical and theoretical implications of this finding for difficult to treat bipolar depressed patients is considerable, and the finding is in need of independent replication. PMID- 21976066 TI - Spikes with short inter-spike intervals in frog retinal ganglion cells are more correlated with their adjacent neurons' activities. AB - Correlated firings among neurons have been extensively investigated; however, previous studies on retinal ganglion cell (RGC) population activities were mainly based on analyzing the correlated activities between the entire spike trains. In the present study, the correlation properties were explored based on burst-like activities and solitary spikes separately. The results indicate that: (1) burst like activities were more correlated with other neurons' activities; (2) burst like spikes correlated with their neighboring neurons represented a smaller receptive field than that of correlated solitary spikes. These results suggest that correlated burst-like spikes should be more efficient in signal transmission, and could encode more detailed spatial information. PMID- 21976068 TI - Comparative study of myocytes from normal and mdx mice iPS cells. AB - Recently, induced pluripotent stem cells (iPS cells) have been derived from various techniques and show great potential for therapy of human diseases. Furthermore, the iPS technique can be used to provide cell models to explore pathological mechanisms of many human diseases in vitro, such as Duchenne muscular dystrophy (DMD), which is a severe recessive X-linked form of muscular dystrophy without effective treatment. In this study, we try to determine whether there are different characteristics of myocytes from mdx iPS cells and C57BL/10 iPS cells. Our results showed that both of mdx and C57BL/10 cells could be induced into iPS cells in vitro, whereas colony-forming ability of mdx iPS cells was much weaker than that of C57BL/10 iPS cells. Meanwhile, mdx iPS cells could be induced to differentiate into myocytes, whereas their differentiation efficiency was much lower than that of C57BL/10 iPS cells. And, the number of apoptotic cells in differentiated myocytes from mdx iPS cells was significantly higher than that from C57BL/10 iPS cells. More importantly, treatment of a pan caspase inhibitor (Z-VAD) produced a significant decrease in apoptotic cells. This study might add some insight to the biology study of dystrophin gene. PMID- 21976069 TI - [Plagiarism techniques in practice journal Johannes Franc (1649-1725) and copying practice illustrated by urology texts]. AB - In the seventeenth century it was customary in medicine to copy texts from other authors without citing the source. This practice is illustrated by the diary of Johannes Franc (1649-1725), a physician in the city of Ulm, who handwrote a practice journal in Latin and German Gothic script entering text passages plagiarized as follows: he reproduced them almost word for word in order to pass them off as his own experiences, used them as a model for his prescriptions and as a template for his case histories, and integrated them into his work to support his argumentation. In addition, he summarized texts from various sources, refined them by omitting portions, and incorporated his own experiences for embellishment. These plagiarism techniques and the purpose they served are analyzed and compared to some passages taken from the original texts. PMID- 21976070 TI - Left hepatectomy. AB - Left hepatectomy is one of the most common types of hepatectomy. In order to perform the procedure, surgeons need to possess all the basic skills for accomplishing any liver resection. The most important points to bear in mind in relation to left hepatectomy are: (1) a precise recognition of the surgical anatomy of the vascular structures of the liver, especially the bile duct, because of the wide anatomic variations; (2) recognition that the procedure consists of the following three parts: hilar dissection, mobilization of the left liver, and liver resection; (3) an understanding that these steps need to be accomplished with great care to control bleeding and to avoid injury to the vessels supplying the right hemiliver. PMID- 21976071 TI - Neutral zinc, lower-order zincate and higher-order zincate derivatives of pyrrole: synthesis and structural characterisation of zinc complexes with one, two, three or four pyrrolyl ligands. AB - Towards a systematic development of the zinc chemistry of the important five membered nitrogen heterocycle pyrrole, this work reports the synthesis and characterisation of five crystalline zinc-pyrrolyl complexes. Pyrrolyl in this context means where conversion of the N-H bond to an N-zinc bond has occurred. Two neutral complexes, [(t)BuZn(NC(4)H(4))(TMEDA).HNC(4)H(4)] 1 and [Zn(NC(4)H(4))(2)(TMEDA)] 2, containing one and two pyrrolyl ligands, respectively, were synthesised by reacting di-t-butylzinc with different amounts of pyrrole in the presence of TMEDA (TMEDA is N,N,N',N' tetramethylethylenediamine). X-ray crystallographic studies established that both adopt mononuclear structures with the salient feature of the former the presence of an additional parent protonated pyrrole molecule which engages its anionic counterpart in N-H...piC-C interactions. Employing a similar synthetic approach but adding n-butylsodium to the reaction mixture in attempts to form ate derivatives delivered three distinct sodium zincate (anionic zinc) compounds in [{(THF)(2).NaZn(THF)(NC(4)H(4))(3)}(infinity)] 3, [{(TMEDA).Na}(2)Zn(NC(4)H(4))(4)] 4, and [{(PMDETA).Na}(2)Zn(NC(4)H(4))(4)] 5 (PMDETA is N,N,N',N'',N''-pentamethyldiethylenetriamine). From their crystal structures, the 1 : 1, Na:Zn complex 3 can be classified as a lower-order zincate having three pyrrolyl ligands bound to zinc in a polymeric chain arrangement, while the 2 : 1, Na:Zn complexes 4 and 5 are molecular higher-order zincates having Zn centres fully saturated by four pyrrolyl ligands. Discussion of the structures of 1-5 focuses on the interplay of sigma-bonding and pi-bonding between the pyrrolyl ligands and the metal centres. Revealingly, the zinc-free sodiopyrrole complex [{(PMDETA).Na(NC(4)H(4))}(2)] 6, made and characterised for comparison, shows that on its own sodium prefers the former type of bonding, but is forced to switch to the latter type when combined with the stronger Lewis acid zinc in the zincate compositions. Complexes 1-6 have also been characterised in solution by NMR spectroscopy. PMID- 21976072 TI - Assessment of genotoxicity induced by 7,12-dimethylbenz(a)anthracene or diethylnitrosamine in the Pig-a, micronucleus and Comet assays integrated into 28 day repeat dose studies. AB - As part of the Stage 3 of the Pig-a international trial, we evaluated 7,12 dimethylbenz(a)anthracene (DMBA) for induction of Pig-a gene mutation using a 28 day repeat dose study design in Sprague-Dawley rats. In the same study, chromosomal damage in peripheral blood and primary DNA damage in liver were also investigated by the micronucleus (MN) assay and the Comet assay, respectively. In agreement with previously published data (Dertinger et al., [2010]: Toxicol Sci 115:401-411), DMBA induced dose-dependent increases of CD59-negative erythrocytes/reticulocytes and micronucleated reticulocytes (MN-RETs). However, there was no significant increase in DNA damage in the liver cells when tested up to 10 mg/kg/day, which appears to be below the maximum tolerated dose. When tested up to 200 mg/kg/day in a follow-up 3 dose study, DMBA was positive in the liver Comet assay. Additionally, we evaluated diethylnitrosamine (DEN), a known mutagen/hepatocarcinogen, for induction of Pig-a mutation, MN and DNA damage in a 28-day study. DEN produced negative results in both the Pig-a mutation assay and the MN assay, but induced dose-dependent increases of DNA damage in the liver and blood Comet assay. In summary, our results demonstrated that the Pig-a mutation assay can be effectively integrated into repeat dose studies and the data are highly reproducible between different laboratories. Also, integration of multiple genotoxicity endpoints into the same study not only provides a comprehensive evaluation of the genotoxic potential of test chemicals, but also reduces the number of animals needed for testing, especially when more than one in vivo genotoxicity tests are required. PMID- 21976073 TI - Slouching towards bethlehem: journal of graduate medical education as midwife. PMID- 21976075 TI - Successfully matching into surgical specialties: an analysis of national resident matching program data. AB - OBJECTIVE: We explored the impact that attributes of US medical school seniors have on their success in matching to a surgical residency, in order to analyze trends for National Resident Matching Program (NRMP) match outcomes in surgical specialties between 2007 and 2009. METHODS: Using Electronic Residency Application Service data and NRMP outcomes, we analyzed medical students' attributes and their effect in successfully matching students into residency positions in surgery, otolaryngology, orthopedic surgery, plastic surgery, and obstetrics and gynecology. Attributes analyzed included self-reported United States Medical Licensing Examination (USMLE) Step 1 and Step 2 scores, Alpha Omega Alpha (AOA) Honor Medical Society membership, research experience, additional graduate degree status, and graduation from a top 40 National Institutes of Health (NIH)-funded medical school. Odds ratios were calculated for each criterion, and 95% confidence intervals were used to determine significance. RESULTS: Between 2007 and 2009, the number of surgical specialty residency positions increased by 86, and the number of applicants increased by 34. Membership in AOA, USMLE Step 1 and Step 2 scores, research experience, and graduation from a top 40 NIH-funded medical school frequently had a significant impact on residents successfully matching into many specialties, while additional graduate degrees had no effect on matching into surgical specialties (range 0.64 to 1.2). CONCLUSIONS: Although the statistical significance varied across specialties, higher USMLE Step 1 and Step 2 scores, AOA membership, research experience, and graduation from a top 40 NIH-funded medical school generally had a positive impact on match success to surgical residency for US allopathic seniors. Test preparation and seeking research experience during undergraduate medical education may be effective approaches for increasing the likelihood of success for US seniors matching into a surgical specialty. PMID- 21976076 TI - Can medical school performance predict residency performance? Resident selection and predictors of successful performance in obstetrics and gynecology. AB - BACKGROUND: During the evaluation process, Residency Admissions Committees typically gather data on objective and subjective measures of a medical student's performance through the Electronic Residency Application Service, including medical school grades, standardized test scores, research achievements, nonacademic accomplishments, letters of recommendation, the dean's letter, and personal statements. Using these data to identify which medical students are likely to become successful residents in an academic residency program in obstetrics and gynecology is difficult and to date, not well studied. OBJECTIVE: To determine whether objective information in medical students' applications can help predict resident success. METHOD: We performed a retrospective cohort study of all residents who matched into the Johns Hopkins University residency program in obstetrics and gynecology between 1994 and 2004 and entered the program through the National Resident Matching Program as a postgraduate year-1 resident. Residents were independently evaluated by faculty and ranked in 4 groups according to perceived level of success. Applications from residents in the highest and lowest group were abstracted. Groups were compared using the Fisher exact test and the Student t test. RESULTS: Seventy-five residents met inclusion criteria and 29 residents were ranked in the highest and lowest quartiles (15 in highest, 14 in lowest). Univariate analysis identified no variables as consistent predictors of resident success. CONCLUSION: In a program designed to train academic obstetrician-gynecologists, objective data from medical students' applications did not correlate with successful resident performance in our obstetrics-gynecology residency program. We need to continue our search for evaluation criteria that can accurately and reliably select the medical students that are best fit for our specialty. PMID- 21976077 TI - Out-of-Match Residency Offers: The Possible Extent and Implications of Prematching in Graduate Medical Education. AB - BACKGROUND: When the data from the National Resident Matching Program (NRMP) are used to analyze trends in medical students' career preferences, positions offered outside the match are omitted. The purpose of the study was to evaluate the extent and nature of out-of-match residency offers. METHODS: We obtained total resident complements and postgraduate year-1 positions offered in 7 specialties in 2007 and compared these with the 2007 NRMP match data. We compared the percentage of positions offered outside the match to "success" in matching United States medical doctors (USMDs) and to the availability of fellowship positions, using the Spearman rank order test (SROT). RESULTS: A total of 18 030 postgraduate year-1 positions were offered in 9 specialty areas. Of 15 205 positions offered in the match, 54% were taken by USMDs. The percentage of outside-the-match offers was found to vary by specialty, from 7% in obstetrics gynecology to 23% in internal medicine, and was inversely correlated with the specialty's "success" in matching USMDs (SROT = -0.87). The 3 nonprocedural primary care specialties (internal medicine, family medicine, and pediatrics) accounted for 10 091 (46.2%) of the 21 845 total positions offered in the match, with 4401 (43.6%) offered almost entirely to non-USMDs. Another 2467 positions were offered outside the match, resulting in 6868 positions offered to non-USMDs (55% of all primary care positions). In internal medicine, the percentage of outside-the-match offers was significantly and inversely associated with the availability of intrainstitutional fellowship programs (P < .0001). Prematching of independent applicants was significantly higher in primary care than in procedural-lifestyle programs (P < .0001). CONCLUSION: The NRMP's match data do not account for positions filled outside the match, a finding that appears to be significant. In 2007, 1 in 5 positions in primary care was offered outside the match. PMID- 21976078 TI - The NRMP's Perspective on Positions Offered Outside the Match: Commentary on: Outside-the-Match Residency Offers: The Possible Extent and Implications of "Prematching" in Postgraduate Medical Education. PMID- 21976079 TI - Potentially discriminatory questions during residency interviews: frequency and effects on residents' ranking of programs in the national resident matching program. AB - BACKGROUND: Medical students rank residency programs as part of the selection process in the National Resident Matching Program, also known as the match. Applicants to medical residency positions are protected against discriminatory employment practices by federal employment laws. OBJECTIVES: To explore students' recall of being asked potentially illegal or discriminatory questions during the selection interview, and whether these questions affected students' ranking of the programs in the match. METHODS: Fourth-year medical students from a single medical school were surveyed after the match. Students were questioned about their recall of the frequency of potentially illegal or discriminatory interview questions and their effect on the program's rank. RESULTS: Ninety percent of the 63 respondents in the study remember being asked at least one potentially discriminatory question. Among these, students were asked about their marital status (86%), about children (31%), about plans for pregnancy (10%), where they were born (54%) and/or about their national origin (15%), and about religious and ethical beliefs (24%). The majority of students did not think the questions changed their decision to rank the program, although the questions changed the way some students ranked the program, either lowering or raising the rank. CONCLUSION: Nearly all students reported that they were asked at least one potentially discriminatory question, although these questions for the most part do not appear to affect whether they ranked the programs. PMID- 21976080 TI - Residents as role models: the effect of the obstetrics and gynecology clerkship on medical students' career interest. AB - BACKGROUND: Medical students' choice of residency specialty is based in part on their clerkship experience. Postclerkship interest in a particular specialty is associated with the students' choice to pursue a career in that field. But, many medical students have a poor perception of their obstetrics and gynecology clerkships. OBJECTIVE: To determine whether fourth-year medical students' perceptions of teaching quality and quantity and amount of experiential learning during the obstetrics-gynecology clerkship helped determine their interest in obstetrics-gynecology as a career choice. METHODS: We distributed an anonymous, self-administered survey to all third-year medical students rotating through their required obstetrics and gynecology clerkship from November 2006 to May 2007. We performed bivariate analysis and used chi(2) analysis to explore factors associated with general interest in obstetrics and gynecology and interest in pursuing obstetrics and gynecology as a career. RESULTS: Eighty-one students (N = 91, 89% response rate) participated. Postclerkship career interest in obstetrics and gynecology was associated with perceptions that the residents behaved professionally (P < .0001) and that the students were treated as part of a team (P = .008). Having clear expectations on labor and delivery procedures (P = .014) was associated with postclerkship career interest. Specific hands-on experiences were not statistically associated with postclerkship career interest. However, performing more speculum examinations in the operating room trended toward having some influence (P = .068). Although more women than men were interested in obstetrics and gynecology as a career both before (P = .027) and after (P = .014) the clerkship, men were more likely to increase their level of career interest during the clerkship (P = .024). CONCLUSIONS: Clerkship factors associated with greater postclerkship interest include higher satisfaction with resident professional behavior and students' sense of inclusion in the clinical team. Obstetrics and gynecology programs need to emphasize to residents their role as educators and professional role models for medical students. PMID- 21976081 TI - Implementation and experience of the first chief residency program in singapore. AB - BACKGROUND: Like their counterparts in many other nations, physicians in Singapore are tasked with providing care, conducting research, and teaching and providing leadership to junior doctors. In this paper, we describe our experience implementing the first chief residency program in Singapore. INITIATIVE: A pilot of a chief residency program was initiated in the Department of Medicine at National University Hospital in July 2008, with 1 chief resident (CR) and 2 associate CR positions. The pilot used the US model for CR training as the initial framework. CRs would assist in the orientation and integration of new residents, teach residents, promote camaraderie among residents, help resolve issues, function as a liaison to senior staff, and would be developed as potential health care leaders and physician role models. RESULTS: The CRs performed a host of administrative duties and initiated several improvements in the residency, including better practices for leave scheduling, call roster planning, and a night float system. CRs attended monthly meetings with division heads and participated in departmental strategic planning as well as professional development and leadership courses. The CR position was well regarded by the other residents, and this resulted in increased interest in identifying and addressing opportunities for improvement. The introduction of a chief residency also made the department a more attractive posting for residents and contributed to a significant increase in the number of applicants for residency rotations. CONCLUSIONS: A chief residency program can benefit residents' morale and a CR's development as a leader, and it can facilitate linkage between junior and senior hospital management that promotes active involvement in problem solving and clinical and education improvement. Support from hospital administrators and senior clinicians is essential, and mentoring and succession planning are important to ensure the program's continued success. PMID- 21976082 TI - The effect of blinded versus nonblinded interviews in the resident selection process. AB - OBJECTIVE: To evaluate whether resident applicants' academic performance biases the assessment of nonacademic qualities. METHODS: In this prospective, descriptive study, 2 blinded (personal statement only) and 1 nonblinded (application) 30-minute interviews were compared for candidates ranking into Top 10, Upper Third, Middle Thirds, Lower Third, and Do Not Rank classes. RESULTS: A total of 234 candidates were interviewed from 2005 to 2007. The association between blinded interviewers for the categories was 87%, 63%, 68%, 73%, and 90% (P = .0000), respectively. Comparing blinded to nonblinded interviewers showed an association of 75% (63%), 71% (86%), 68% (58%), 66% (79%), and 72.7% (82%) (P = .0000), respectively. A strong degree of agreement (Cohen kappa, 0.75) for the 2 ranking scores resulted in 90% agreement for Top 10 and Upper Third and 85% for Middle Third and Lower Third categories. No correlation was found between United States Medical Licensing Examination scores and final ranking; moderate agreement was found between ranking and deans' letters (Cohen kappa, 0.59, P = .0000). CONCLUSION: Candidate rankings on nonacademic attributes were not affected by interview type. PMID- 21976083 TI - Evidence for increasing diversity in graduate medical education: the competence of underrepresented minority residents measured by an intern objective structured clinical examination. AB - OBJECTIVE: Some have commented that the limited number of underrepresented minorities (URMs) in United States' residency programs is due to a lack of qualified candidates. At the University of Michigan, an objective structured clinical examination is administered to incoming residents at the beginning of training to determine baseline competence. In this study we wanted to determine if competence differed for underrepresented minorities when compared to non-URM residents. METHOD: The postgraduate orientation assessment, a 10-station examination, was developed that focused specifically on the knowledge and skills needed in the first 6 to 18 weeks of training. Stations assessed competence in informed consent, aseptic technique, evidence-based medicine, diagnostic images, critical laboratory values, cross-cultural communication, and Joint Commission requirements such as surgical fire safety, pain assessment, and management. We used various assessment measures including standardized patients, computer-based testing, and multiple-choice questions. RESULTS: Our study found no significant differences in overall mean scores between URM residents and all other residents for the 5 years during which we administered the examination, except for 2002. This stands in contrast to the consistently worse performances of URM students on USMLE Step 1 and Step 2 Clinical Knowledge. Also, URM residents did not perform better or worse than their non-URM colleagues on standardized patient stations during the course of 5 years during which the examination was administered. CONCLUSIONS: The postgraduate orientation assessment provides residency program directors with a standard format to measure initial clinical skills. When compared to incoming non-URM residents from a variety of medical schools, URM residents perform as well as other trainees. Our results may aid in the recruitment efforts of URM medical students into academic residency programs such as those at the University of Michigan. PMID- 21976084 TI - Match rates into higher-income, controllable lifestyle specialties for students from highly ranked, research-based medical schools compared with other applicants. AB - BACKGROUND: Factors impacting medical student specialty career choice are poorly understood, but may include income potential and lifestyle features such as limited and predictable work hours. METHODS: Data from the National Resident Matching Program and the San Francisco Match were used to examine match rates into higher-income controllable lifestyle (CL), lower-income CL, and noncontrollable lifestyle (NCL) specialties from 2002 to 2007. We studied 3 cohorts: students from highly ranked, research-based medical schools, other US senior medical students, and independent applicants (consisting mostly of graduates from foreign medical schools). RESULTS: By 2007, 22.5% of students from highly ranked schools matched into a higher-income CL specialty compared with 16.5% of other US seniors and 8.4% of independent applicants. During the study period, students from highly ranked schools increased their match rate in higher income CL specialties by 7.9%, while all cohorts experienced declines in match rates for NCL specialties. Compared with other US seniors, students from highly ranked schools were more likely to match into higher-income CL specialties (odds ratio [OR], 1.46; 95% confidence interval [CI]: 1.27-1.68), while independent applicants were much less likely to do so (OR, 0.46; 95% CI: 0.42-0.51). Independent applicants had the highest odds (OR, 2.38; 95% CI: 2.25-2.52) of matching into NCL specialties. CONCLUSIONS: All cohorts had declining match rates into NCL specialties from 2002 to 2007. When compared with other US seniors, students from highly ranked schools had the highest odds of matching in higher income CL specialties, while independent applicants had the highest odds of matching into NCL specialties. These trends are important to consider in light of recent efforts to better balance the physician workforce. PMID- 21976085 TI - Evaluation of a transition to practice program for neurosurgery residents: creating a safe transition from resident to independent practitioner. AB - BACKGROUND: In 2004, the Department of Neurosurgery at the University of Florida implemented a major curriculum innovation called the Transition to Practice program. This program was established to prepare residents to more safely transition to the role of independent practitioner. METHODS: A qualitative and quantitative evaluation of the program was conducted after its fifth year using online surveys and interviews. Study participants included Transition to Practice graduates, faculty, and current residents. RESULTS: Of the 26 respondents, 89% of faculty and all graduates were very satisfied with the program. Strengths identified included an independent yet mentored broad operative experience, the development of self-confidence, and a real sense of responsibility for patients. Medical billing and coding instruction and career mentoring were areas of the program that required additional attention. CONCLUSION: Overall, this program is meeting the stated objectives and is well received by the graduates and faculty. Based on the results of this evaluation, curricular changes such as instructions in practice management and implementation of a career-mentoring program have occurred. The Transition to Practice program is a unique curricular response to change that other surgical specialties may find useful in addressing the current day stresses on graduate medical education. PMID- 21976086 TI - Medicine in the 21st century: recommended essential geriatrics competencies for internal medicine and family medicine residents. AB - BACKGROUND: Physician workforce projections by the Institute of Medicine require enhanced training in geriatrics for all primary care and subspecialty physicians. Defining essential geriatrics competencies for internal medicine and family medicine residents would improve training for primary care and subspecialty physicians. The objectives of this study were to (1) define essential geriatrics competencies common to internal medicine and family medicine residents that build on established national geriatrics competencies for medical students, are feasible within current residency programs, are assessable, and address the Accreditation Council for Graduate Medical Education competencies; and (2) involve key stakeholder organizations in their development and implementation. METHODS: Initial candidate competencies were defined through small group meetings and a survey of more than 100 experts, followed by detailed item review by 26 program directors and residency clinical educators from key professional organizations. Throughout, an 8-member working group made revisions to maintain consistency and compatibility among the competencies. Support and participation by key stakeholder organizations were secured throughout the project. RESULTS: The process identified 26 competencies in 7 domains: Medication Management; Cognitive, Affective, and Behavioral Health; Complex or Chronic Illness(es) in Older Adults; Palliative and End-of-Life Care; Hospital Patient Safety; Transitions of Care; and Ambulatory Care. The competencies map directly onto the medical student geriatric competencies and the 6 Accreditation Council for Graduate Medical Education Competencies. CONCLUSIONS: Through a consensus building process that included leadership and members of key stakeholder organizations, a concise set of essential geriatrics competencies for internal medicine and family medicine residencies has been developed. These competencies are well aligned with concerns for residency training raised in a recent Medicare Payment Advisory Commission report to Congress. Work is underway through stakeholder organizations to disseminate and assess the competencies among internal medicine and family medicine residency programs. PMID- 21976087 TI - Teaching and assessing systems-based practice: a pilot course in health care policy, finance, and law for radiation oncology residents. AB - BACKGROUND: Under the Accreditation Council for Graduate Medical Education (ACGME) Outcome Project, residency programs are required to provide data on educational outcomes and evidence for how this information is used to improve resident education. OBJECTIVE: To teach and assess systems-based practice through a course in health care policy, finance, and law for radiation oncology residents, and to determine its efficacy. METHODS AND MATERIALS: We designed a pilot course in health care policy, finance, and law related to radiation oncology. Invited experts gave lectures on policy issues important to radiation oncology and half of the participants attended the American Society for Therapeutic Radiation and Oncology (ASTRO) Advocacy Day. Participants completed pre- and postcourse tests to assess their knowledge of health policy. RESULTS: Six radiation oncology residents participated, with 5 (84%) completing all components. For the 5 residents completing all assessments, the mean precourse score was 64% and the mean postcourse score was 84% (P = .05). Improvement was noted in all 3 sections of health policy, finance, and medical law. At the end of the course, 5 of 6 residents were motivated to learn about health policy, and 4 of 6 agreed it was important for physicians to be involved in policy matters. CONCLUSIONS: Teaching radiation oncology residents systems-based practice through a course on health policy, finance, and law is feasible and was well received. Such a course can help teaching programs comply with the ACGME Outcome Project and would also be applicable to trainees in other specialties. PMID- 21976088 TI - Creating and evaluating a data-driven curriculum for central venous catheter placement. AB - BACKGROUND: Central venous catheter placement is a common procedure with a high incidence of error. Other fields requiring high reliability have used Failure Mode and Effects Analysis (FMEA) to prioritize quality and safety improvement efforts. OBJECTIVE: To use FMEA in the development of a formal, standardized curriculum for central venous catheter training. METHODS: We surveyed interns regarding their prior experience with central venous catheter placement. A multidisciplinary team used FMEA to identify high-priority failure modes and to develop online and hands-on training modules to decrease the frequency, diminish the severity, and improve the early detection of these failure modes. We required new interns to complete the modules and tracked their progress using multiple assessments. RESULTS: Survey results showed new interns had little prior experience with central venous catheter placement. Using FMEA, we created a curriculum that focused on planning and execution skills and identified 3 priority topics: (1) retained guidewires, which led to training on handling catheters and guidewires; (2) improved needle access, which prompted the development of an ultrasound training module; and (3) catheter-associated bloodstream infections, which were addressed through training on maximum sterile barriers. Each module included assessments that measured progress toward recognition and avoidance of common failure modes. Since introducing this curriculum, the number of retained guidewires has fallen more than 4-fold. Rates of catheter-associated infections have not yet declined, and it will take time before ultrasound training will have a measurable effect. CONCLUSION: The FMEA provided a process for curriculum development. Precise definitions of failure modes for retained guidewires facilitated development of a curriculum that contributed to a dramatic decrease in the frequency of this complication. Although infections and access complications have not yet declined, failure mode identification, curriculum development, and monitored implementation show substantial promise for improving patient safety during placement of central venous catheters. PMID- 21976089 TI - Women's Health Curriculum for Internal Medicine Residents: Development, Implementation, and Evaluation. AB - OBJECTIVE: Women's health knowledge and skills are important for physicians, but training is often inadequate. The objective of this project was to develop, implement, and evaluate a women's health curriculum for an internal medicine residency program. METHODS: After assessing institutional factors, we developed a curriculum for a multidisciplinary clinical rotation with a web-based tutorial. We recruited faculty from several specialties relevant to the care of women to precept for the rotation and/or to provide teaching materials for the tutorial. RESULTS: The curriculum for the 1-month rotation covered most of the recommended women's health topics. Internal medicine residents worked in a variety of clinical settings and were assigned to a web-based tutorial and a pretest and posttest. A statistically significant increase was seen in participants' mean posttest (71.7%) versus pretest (61.1%) scores (difference, 10.7%; 95% confidence interval [CI]: 4.7-16.6; P = .0009). No difference was seen in controls' mean posttest (56.5%) versus pretest (57.2%) scores (difference, -0.7%; 95% CI: -12.1 10.7; P = .9). Mean rotation evaluation responses ranged from 7.09 to 7.45 on a 9-point scale. The majority (93%) of survey respondents agreed that the rotation increased their skills in caring for women, and all agreed the program was well organized and that it increased their awareness of women's health issues. CONCLUSION: A women's health curriculum using a web-based tutorial with a multidisciplinary clinical rotation can be successfully implemented in an internal medicine residency. The curriculum satisfied women's health training requirements, was associated with improvements in learning outcomes, and may be a model for women's health education. PMID- 21976090 TI - Acute coronary syndrome and cardiac arrest: using simulation to assess resident performance and program outcomes. AB - BACKGROUND: Simulation training has emerged as an effective method of educating residents in cardiac emergencies. Few studies have used emergency simulation scenarios as an outcome measure to identify training deficiencies within residency programs. PURPOSE: The purpose of this study was to evaluate postgraduate year-1 (PGY-1) residents on their ability to manage an acute coronary syndrome and cardiac arrest scenario before and after internship in order to provide outcome data to improve program performance. METHODS: A total of 58 PGY-1 residents from 10 medical specialties were evaluated using a human patient simulator before and after internship. They were given 12 minutes to manage a patient with acute coronary syndrome and ventricular fibrillation due to hyperkalemia. An objective checklist following basic and advanced cardiac life support guidelines was used to assess performance. RESULTS: A total of 58 interns (age, 25 to 44 years [mean, 29.1]; 38 [65.6%] men; 41 [70.7%] allopathic medical school graduates) participated in both the incoming and outgoing examination. Overall chest pain scores increased from a mean of 60.0% to 76.1% (P < .01). Medical knowledge performance improved from 51.1% to 76.1% (P < .01). Systems based practice performance improved from 40.9% to 71.0% (P < .01). However, patient care performance declined from 93.4% to 80.2% (P < .01). CONCLUSIONS: A simulated acute coronary syndrome and cardiac arrest scenario can evaluate incoming PGY-1 competency performance and test for interval improvement. This assessment tool can measure resident competency performance and evaluate program effectiveness. PMID- 21976091 TI - The pediatrics milestones: conceptual framework, guiding principles, and approach to development. AB - BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) and the American Board of Pediatrics (ABP) have partnered to initiate the Pediatrics Milestone Project to further refine the 6 ACGME competencies and to set performance standards as part of the continued commitment to document outcomes of training and program effectiveness. INTERVENTION: Members of the Pediatrics Milestone Project Working Group searched the medical literature and beyond to create a synopsis of models and evidence for a developmental ontogeny of the elements for 52 subcompetencies. For each subcompetency, we created a series of Milestones, grounded in the literature. The milestones were vetted with the entire working group, engaging in an iterative process of revisions until reaching consensus that their narrative descriptions (1) included all critical elements, (2) were behaviorally based, (3) were properly sequenced, and (4) represented the educational continuum of training and practice. OUTCOMES: We have completed the first iteration of milestones for all subcompetencies. For each milestone, a synopsis of relevant literature provides background, references, and a conceptual framework. These milestones provide narrative descriptions of behaviors that represent the ontogeny of knowledge, skill, and attitude development across the educational continuum of training and practice. DISCUSSION: The pediatrics milestones take us a step closer to meaningful outcome assessment. Next steps include undertaking rigorous study, making appropriate modifications, and setting performance standards. Our aim is to assist program directors in making more reliable and valid judgments as to whether a resident is a "good doctor" and to provide outcome evidence regarding the program's success in developing doctors. PMID- 21976092 TI - Beyond competencies and milestones: adding meaning through context. PMID- 21976093 TI - Evaluating professionalism, practice-based learning and improvement, and systems based practice: utilization of a compliance form and correlation with conflict styles. AB - OBJECTIVE: The purpose of this article was to develop and determine the utility of a compliance form in evaluating and teaching the Accreditation Council for Graduate Medical Education competencies of professionalism, practice-based learning and improvement, and systems-based practice. METHODS: In 2006, we introduced a 17-item compliance form in an obstetrics and gynecology residency program. The form prospectively monitored residents on attendance at required activities (5 items), accountability of required obligations (9 items), and completion of assigned projects (3 items). Scores were compared to faculty evaluations of residents, resident status as a contributor or a concerning resident, and to the residents' conflict styles, using the Thomas-Kilmann Conflict MODE Instrument. RESULTS: Our analysis of 18 residents for academic year 2007-2008 showed a mean (standard error of mean) of 577 (65.3) for postgraduate year (PGY)-1, 692 (42.4) for PGY-2, 535 (23.3) for PGY-3, and 651.6 (37.4) for PGY-4. Non-Hispanic white residents had significantly higher scores on compliance, faculty evaluations on interpersonal and communication skills, and competence in systems-based practice. Contributing residents had significantly higher scores on compliance compared with concerning residents. Senior residents had significantly higher accountability scores compared with junior residents, and junior residents had increased project completion scores. Attendance scores increased and accountability scores decreased significantly between the first and second 6 months of the academic year. There were positive correlations between compliance scores with competing and collaborating conflict styles, and significant negative correlations between compliance with avoiding and accommodating conflict styles. CONCLUSIONS: Maintaining a compliance form allows residents and residency programs to focus on issues that affect performance and facilitate assessment of the ACGME competencies. Postgraduate year, behavior, and conflict styles appear to be associated with compliance. A lack of association with faculty evaluations suggests measurement of different perceptions of residents' behavior. PMID- 21976094 TI - Use of a 360-degree evaluation in the outpatient setting: the usefulness of nurse, faculty, patient/family, and resident self-evaluation. AB - BACKGROUND: Faculty have traditionally evaluated resident physician professionalism and interpersonal skills without input from patients, family members, nurses, or the residents themselves. The objective of our study was to use "360-degree evaluations," as suggested by the Accreditation Council for Graduate Medical Education (ACGME), to determine if nonfaculty ratings of resident professionalism and interpersonal skills differ from faculty ratings. METHODS: Pediatrics residents were enrolled in a hospital-based resident continuity clinic during a 5-week period. Patient/families (P/Fs), faculty (MD [doctor of medicine]), nurses (RNs [registered nurses]), and residents themselves (self) completed evaluator-specific evaluations after each clinic session by using a validated 10-item questionnaire with a 5-point Likert scale. The average Likert score was tallied for each questionnaire. Mean Likert scale scores for each type of rater were compared by using analysis of variance, text with pair wise comparisons when appropriate. Agreement between rater types was measured by using the Pearson correlation. RESULTS: A total of 823 evaluations were completed for 66 residents (total eligible residents, 69; 95% participation). All evaluators scored residents highly (mean Likert score range, 4.4 to 4.9). However, MDs and RNs scored residents higher than did P/Fs (mean scores: MD, 4.77, SD [standard deviation], 0.32; RN, 4.85, SD, 0.30; P/F, 4.53, SD, 0.96; P < .0001). MD and RN scores also were higher than residents' self-evaluation scores, but there was no difference between self-scores and P/F scores (average resident self-score, 4.44, SD, 0.43; P < .0001 compared to MD and RN; P = .19 compared to P/F). Correlation coefficients between all combinations of raters ranged from 0.21 to 0.21 and none were statistically significant. CONCLUSION: Our study found high ratings for resident professionalism and interpersonal skills. However, different members of the health care team rated residents differently, and ratings are not correlated. Our results provide evidence for the potential value of 360-degree evaluations. PMID- 21976095 TI - Validation of an online assessment of orthopedic surgery residents' cognitive skills and preparedness for carpal tunnel release surgery. AB - BACKGROUND: Surgical competence requires both cognitive and technical skills. Relatively little is found in the literature regarding the value of Web-based assessments to measure surgery residents' mastery of the competencies. OBJECTIVE: To determine the validity and reliability of 2 online instruments for predicting the cognitive preparedness of residents for performing carpal tunnel release surgery. METHOD: Twenty-eight orthopedic residents and 2 medical school students responded to an online measure of their perception of preparedness and to an online cognitive skills assessment prior to an objective structured assessment of technical skills, in which they performed carpal tunnel release surgery on cadaveric specimens and received a pass/fail assessment. The 2 online assessments were analyzed for their internal reliability, external correlation with the pass/fail decision, and construct validity. RESULTS: The internal consistency of the perception of preparedness measure was high (alpha = .92) while the cognitive assessment was less strong (alpha = .65). Both instruments demonstrated moderately strong correlations with the pass/fail decision, with Spearman correlation of .606 (P = .000) and .617 (P = .000), respectively. Using logistic regression to analyze the predictive strength of each instrument, the perception of preparedness measure demonstrated a 76% probability (eta(2) = .354) and the cognitive skills assessment a 73% probability (eta(2) = .381) of correctly predicting the pass/fail decision. Analysis of variance modeling resulted in significant differences between levels at P < .005, supporting good construct validity. CONCLUSIONS: The online perception of preparedness measure and the cognitive skills assessment both are valid and reliable predictors of readiness to successfully pass a cadaveric motor skills test of carpal tunnel release surgery. PMID- 21976096 TI - Direct versus indirect supervision of fellows covering football events: a survey of fellows and program directors. AB - BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) program requirements mandate "adequate supervision," of residents, but there is little guidance for sports medicine fellowship directors regarding the transition from direct to indirect supervision of fellows covering football games. OBJECTIVE: We sought to gather evidence of current supervision practices in the context of injury outcomes. METHODS: Fellows and program directors of ACGME accredited sports medicine fellowship programs were invited to complete an online survey regarding their experience and current supervision practice at football games. Criteria for transition to autonomy and desired changes in supervision practice were elicited. Player safety was quantified by noting the number of field-side emergencies, whether an attending was present, and whether better outcomes might have resulted from the presence of an attending. RESULTS: A total of 80 fellows and 50 program directors completed the online survey. Direct supervision was lacking in about 50% of high school games and 20% of college games. A resulting cost in terms of player safety was estimated to apply to 5% of serious injuries by fellows' report but less than 0.5% by directors' report. Written criteria for transitioning from direct supervision to autonomy were the exception rather than the rule. The majority of fellows and directors expressed satisfaction with the current level of supervision, but 20% of fellows would prefer more supervision through postgame review. CONCLUSIONS: Football games covered by fellows are often not directly supervised. Absence of an attending affected the outcomes of 5% or less of serious injuries. Transition to autonomy does not usually require meeting written criteria. Fellows might benefit from additional off-site supervision. PMID- 21976097 TI - Reflective practice and competencies in global health training: lesson for serving diverse patient populations. AB - BACKGROUND: Resident interest in global health care training is growing and has been shown to have a positive effect on participants' clinical skills and cultural competency. In addition, it is associated with career choices in primary care, public health, and in the service of underserved populations. The purpose of this study was to explore, through reflective practice, how participation in a formal global health training program influences pediatric residents' perspectives when caring for diverse patient populations. METHODS: Thirteen pediatric and combined-program residents enrolled in a year-long Global Health Scholars Program at Cincinnati Children's Hospital Medical Center during the 2007 2008 academic year. Educational interventions included a written curriculum, a lecture series, one-on-one mentoring sessions, an experience abroad, and reflective journaling assignments. The American Society for Tropical Medicine and Hygiene global health competencies were used as an a priori coding framework to qualitatively analyze the reflective journal entries of the residents. RESULTS: Four themes emerged from the coded journal passages from all 13 residents: (1) the burden of global disease, as a heightened awareness of the diseases that affect humans worldwide; (2) immigrant/underserved health, reflected in a desire to apply lessons learned abroad at home to provide more culturally effective care to immigrant patients in the United States; (3) parenting, or observed parental, longing to assure that their children receive health care; and (4) humanitarianism, expressed as the desire to volunteer in future humanitarian health efforts in the United States and abroad. CONCLUSIONS: Our findings suggest that participating in a global health training program helped residents begin to acquire competence in the American Society for Tropical Medicine and Hygiene competency domains. Such training also may strengthen residents' acquisition of professional skills, including the Accreditation Council for Graduate Medical Education competencies. PMID- 21976098 TI - The neighborhood health exchange: developing a community partnership in residency. AB - BACKGROUND: The current system of residency training focuses on the hospital setting, and resident exposure to the surrounding community is often limited. However, community interaction can play an important role in ambulatory training and in learning systems-based practice, a residency core competency. The goal of the Neighborhood Health Exchange was to develop a community partnership to provide internal medicine residents with an opportunity to interface with community members through a mutually beneficial educational experience. METHODS: Internal medicine residents received training during their ambulatory block and participated in a voluntary field practicum designed to engage community members in discussions about their health. Community members participated in education sessions led by resident volunteers. RESULTS: Resident volunteers completed a survey on their experiences. All residents stated that the opportunity to lead an exchange was very useful to their overall residency training. Eight exchanges were held with a total of 61 community participants, who completed a 3-question survey following the session. This survey asked about the level of material, the helpfulness of the exchanges, and opportunities for improvement. We received 46 completed surveys from community members: 91% stated that the material was presented "at the right level" and 93% stated that the presentations were somewhat or very helpful. Eighty percent gave positive and encouraging comments about the exchange. CONCLUSION: Effective community partnerships involve assessing needs of the stakeholders, anticipating leadership turnover, and adapting the Neighborhood Health Exchange model to different groups. Community outreach can also enhance internal medicine ambulatory training experience, provide residents with patient counseling opportunities, and offer a novel method to enhance resident understanding of systems-based practice, especially within the larger community in which their patients live. PMID- 21976099 TI - Postgraduate year-1 residency training in emergency psychiatry: an acute care psychiatric clinic at a community mental health center. AB - OBJECTIVE: The purpose of this study was to determine resident satisfaction with an acute care psychiatric clinic designed in collaboration with a nearby community mental health center. We also sought to demonstrate that this rotation helps meet program requirements for emergency psychiatry training, provides direct assessments of resident interviewing skills and clinical knowledge in the postgraduate year-1, and provides exposure to public sector systems of care. METHODS: We developed a resident satisfaction questionnaire and fielded it to each of the residents who participated in the clinic over the first 3 years. Data were collected, organized, and analyzed. RESULTS: Of the 15 residents in the acute care psychiatric clinic, 12 completed and returned the satisfaction questionnaires. Educational aspects of the clinic experience were rated favorably. CONCLUSIONS: This postgraduate year-1 acute care psychiatric clinic provides a mechanism for the fulfillment of emergency psychiatry training as well as direct supervision of clinical encounters, which is a satisfactory and useful educational experience for trainees. PMID- 21976100 TI - Quality of cardiovascular care in an internal medicine resident clinic. AB - BACKGROUND: Attainment of treatment goals derived from evidence-based practice guidelines can be a useful measure of the quality of cardiovascular care. To date, there are few studies of the quality of care provided in a resident continuity clinic, as measured by success in meeting nationally defined guidelines for control of cardiovascular risk factors. There also is limited information regarding the quality of care in resident continuity clinics serving multiethnic uninsured/underinsured populations. This study assessed the efficacy of residents in internal medicine in attaining evidence-based, guideline-defined treatment goals for control of hypertension, dyslipidemia, and hyperglycemia in an uninsured/underinsured multiethnic population. METHODS: In a cross-sectional study of patients treated exclusively by residents (with faculty supervision) between July 1 and December 31, 2005, data were abstracted from the medical records of 628 consecutive patients (mean age, 55.6 years; 62% female; 61.3% non white; 55.5% uninsured) with hypertension, hyperlipidemia, and/or diabetes mellitus. Quality measures were the proportion of diabetic and nondiabetic patients who met guideline-defined treatment goals for hypertension, dyslipidemia, and hyperglycemia in diabetic patients. RESULTS: Goal attainment overall was 44.9% for high blood pressure, 55.7% for dyslipidemia, and 43.3% for hemoglobin A(1c) for diabetic patients. There was no relationship between age, gender, race/ethnicity, insurance, or body weight to attainment of hypertension, dyslipidemia, or hemoglobin A(1c) goals in diabetic and nondiabetic cohorts from multivariate analysis. Risk factor control rates were higher in this study than in comparable educational programs. CONCLUSION: An internal medicine resident continuity clinic can provide high-quality care that meets guideline-defined cardiovascular risk factor control goals in a racially and ethnically diverse, underinsured/uninsured, low-income population in a community-based academic medical center. PMID- 21976101 TI - Practice-based learning and systems-based practice: detection and treatment monitoring of generalized anxiety and depression in primary care. AB - OBJECTIVES: Quality assurance/quality improvement projects are an important part of professional development in graduate medical education. The purpose of our quality improvement study was to evaluate whether (1) the Generalized Anxiety Disorder (GAD-7) scale questionnaire increases detection of anxiety and (2) the Quick Inventory for Depressive Symptomatology Self Report (QIDS-SR) increases detection of depression in a primary care setting. We also aimed to determine whether monitoring patients with depression or generalized anxiety using the QIDS SR and GAD-7 scales influences treatment changes in the primary care setting. METHODS: Patients seen in a general internal medicine clinic between August 2008 and March 2009 were asked to fill out the QID-SR questionnaire and GAD-7 as part of a resident quality improvement project. We measured the prevalence of anxiety and depression during 6 months prior to the use of the GAD-7 and QIDS-SR instruments during the intervention period. We also compared the frequency of treatment changes initiated both 12 months prior to and during the intervention period. The aforementioned measures were performed with use of a retrospective chart review. RESULTS: The prevalence of anxiety was 15.2% in the pre intervention period and 33.3% in the intervention period, and the prevalence of depression was 38.9% in the prescreening period and 54.8% during the screening period (P value for both was <0.001). The change in anxiety therapy was 21.6% in the prescreening period and 62.2% in the screening period (P = .028). The change in depression therapy was 23.2% in the pre-intervention period and 52.1% in the intervention period (P = .025). CONCLUSION: Routine screening for depression and anxiety may help clinicians detect previously undiagnosed anxiety and depression and also may facilitate identification of needed treatment changes. Further work is needed to determine whether routine screening improves patient outcomes. PMID- 21976102 TI - Advantages and challenges of working as a clinician in an academic department of medicine: academic clinicians' perspectives. AB - BACKGROUND: The provision of high-quality clinical care is critical to the mission of academic and nonacademic clinical settings and is of foremost importance to academic and nonacademic physicians. Concern has been increasingly raised that the rewards systems at most academic institutions may discourage those with a passion for clinical care over research or teaching from staying in academia. In addition to the advantages afforded by academic institutions, academic physicians may perceive important challenges, disincentives, and limitations to providing excellent clinical care. To better understand these views, we conducted a qualitative study to explore the perspectives of clinical faculty in prominent departments of medicine. METHODS: Between March and May 2007, 2 investigators conducted in-depth, semistructured interviews with 24 clinically excellent internal medicine physicians at 8 academic institutions across the nation. Transcripts were independently coded by 2 investigators and compared for agreement. Content analysis was performed to identify emerging themes. RESULTS: Twenty interviewees (83%) were associate professors or professors, 33% were women, and participants represented a wide range of internal medicine subspecialties. Mean time currently spent in clinical care by the physicians was 48%. Domains that emerged related to faculty's perception of clinical care in the academic setting included competing obligations, teamwork and collaboration, types of patients and productivity expectations, resources for clinical services, emphasis on discovery, and bureaucratic challenges. CONCLUSIONS: Expert clinicians at academic medical centers perceive barriers to providing excellent patient care related to competing demands on their time, competing academic missions, and bureaucratic challenges. They also believe there are differences in the types of patients seen in academic settings compared with those in the private sector, that there is a "public" nature in their clinical work, that productivity expectations are likely different from those of private practitioners, and that resource allocation both facilitates and limits excellent care in the academic setting. These findings have important implications for patients, learners, and faculty and academic leaders, and suggest challenges as well as opportunities in fostering clinical medicine at academic institutions. PMID- 21976103 TI - Professional bankruptcy for the academic physician. AB - In modern academic medicine, the amount of academic time is decreasing as the workload and commitments are increasing. As physicians take on so many professional obligations that there is no way to meet all of the demands of the ever-expanding responsibilities, the question becomes: Should academic physicians ever consider filing for their own "professional bankruptcy"? Presented here are 10 steps to successful academic bankruptcy for the overextended junior faculty. Although somewhat fanciful, this method allows faculty to take an honest and critical assessment of their personal and professional goals and to align their career with these goals. With a critical eye to the future, this alignment will allow faculty to decrease their workload while maintaining productivity. PMID- 21976104 TI - Commentary: clinical faculty, academic culture, and the future of medical professionalism. PMID- 21976105 TI - A retrospective study of tibial plateau translation following tibial plateau levelling osteotomy stabilisation using three different plate types. AB - OBJECTIVE: To retrospectively evaluate mediolateral translation of the proximal tibial segment (tibial plateau) after tibial plateau levelling osteotomy (TPLO), stabilised with three types of plate. METHOD: Pre- and postoperative radiographs of 79 dogs that had TPLO surgery using three different types of plates were reviewed. Two plate types incorporated non-locking screws: Slocum (22 cases) and Orthomed Delta (33 cases) plates. The third plate type incorporated locking screws: Synthes TPLO Locking Compression Plate (LCP) (24 cases). The radiographs were viewed by three Diplomate surgeons who were blinded to the type of implant used. Medial or lateral translation of the proximal tibial plateau relative to the tibial diaphysis was assessed and measured at the lateral tibial cortex at the osteotomy site. RESULTS: Mean lateral translation of the tibial plateau was significantly greater when using the Synthes TPLO LCP with locking screws (+2.1 mm) compared to the non-locking Slocum (+0.4 mm) or Orthomed Delta (0.0 mm) plates. CLINICAL SIGNIFICANCE: The use of the Synthes TPLO LCP will maintain a malalignment of the tibial plateau. Accurate alignment of the tibial plateau must be ensured prior to application of the Synthes TPLO LCP. PMID- 21976106 TI - Evaluation of circulating soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) to predict risk profile, response to antimicrobial therapy, and development of complications in patients with chemotherapy-associated febrile neutropenia: a pilot study. AB - The soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) is a useful marker of infection in patients with sepsis, but has not been adequately evaluated in patients with chemotherapy-associated febrile neutropenia (FN). The value of sTREM-1 in this setting has been tested in a retrospective, pilot study using stored serum from 48 cancer patients with documented FN. On presentation, patients were categorized according to the Talcott risk-index clinical score. Circulating soluble sTREM-1 was measured using an ELISA procedure, while procalcitonin (PCT) or interleukins 6 (IL-6) and 8 (IL-8), included for comparison, were measured using an immunoluminescence-based assay and Bio-Plex(r) suspension bead array system, respectively. Circulating concentrations of both sTREM-1 and PCT were significantly (P < 0.05) elevated in patients at high risk for complications or death, as predicted by the Talcott score and were significantly lower in patients who responded to empiric antimicrobial agents. Neither IL-6 nor IL-8 accurately predicted serious complications in patients with FN. These observations, albeit from a pilot study, demonstrate that sTREM-1 is indeed elevated in high-risk patients with FN and is potentially useful to predict their clinical course, either together with, or as an alternative to PCT. PMID- 21976107 TI - Successful transfusion care for a patient with the Rhesus -D- phenotype and antibodies against Rh17 and two additional alloantibodies. PMID- 21976108 TI - Vincristine-induced vocal cord paralysis in a patient with acute lymphoblastic leukemia. PMID- 21976110 TI - A hot-melt extruded intravaginal ring for the sustained delivery of the antiretroviral microbicide UC781. AB - Microbicide intravaginal rings (IVRs) are a promising woman-controlled strategy for preventing sexual transmission of human immunodeficiency virus (HIV). An IVR was prepared and developed from polyether urethane (PU) elastomers for the sustained delivery of UC781, a highly potent nonnucleoside reverse transcriptase inhibitor of HIV-1. PU IVRs containing UC781 were fabricated using a hot-melt extrusion process. In vitro release studies of UC781 demonstrated that UC781 release profiles are loading dependent and resemble matrix-type, diffusion limited kinetics. The in vitro release methods employed over predicted the in vivo release rates of UC781 in rabbits. Accelerated stability studies showed good chemical stability of UC781 in prototype formulations, but surface crystallization of UC781 was observed following long-term storage at higher UC781 loadings, unless formulated with a polyvinylpyrrolidone/glycerol surface coating. Mechanical stability testing of prototype rings showed moderate stiffening upon storage. The PU and UC781 had minimal to no impact on viability, tissue integrity, barrier function, or cytokine expression in the tissue irritation model, and UC781 was shown to be delivered to and permeate through this tissue construct in vitro. Overall, UC781 was formulated in a stable PU IVR and provided controlled release of UC781 both in vitro and in vivo. PMID- 21976111 TI - ATR controls the p21(WAF1/Cip1) protein up-regulation and apoptosis in response to low UV fluences. AB - The universal cyclin-dependent kinase inhibitor p21(WAF1/Cip1) promotes cell cycle arrest and inhibits apoptosis in response to UV-induced DNA damage. Since the protein kinase ATR plays a major role in the cellular response to these carcinogenic lesions, we investigated the possible role of ATR in the modulation of p21(WAF1/Cip1) expression in response to UVC radiation. We have shown that p21(WAF1/Cip1) is up-regulated in human fibroblast and epithelial cells, but only in response to low UV fluences and low passage cells. Importantly, this up regulation is ATR-dependent. In fact, in ATR-deficient or caffeine-treated cells UV light rather down-regulated the p21(WAF1/Cip1) protein through SKP2-dependent ubiquitination and degradation via the proteasomal pathway. Furthermore, we present evidence that ATR inhibits apoptosis in response to low fluences of UV light, through inhibiting the cleavage of caspase 3 and PARP as well as the repression of the proapoptotic proteins BAX and BAK. Interestingly, ATR is also required for the stability of the p21(WAF1/Cip1) protein in absence of genotoxic stress. Together, these results indicate that during the cellular response to low UVC fluences the ATR protein kinase up-regulates p21(WAF1/Cip1) and inhibits apoptosis. (c) 2011 Wiley Periodicals, Inc. PMID- 21976109 TI - Association of obesity-related genetic variants with endometrial cancer risk: a report from the Shanghai Endometrial Cancer Genetics Study. AB - Obesity is a well-established risk factor for endometrial cancer, the most common gynecologic malignancy. Recent genome-wide association studies (GWAS) have identified multiple genetic markers for obesity. The authors evaluated the association of obesity-related single nucleotide polymorphisms (SNPs) with endometrial cancer using GWAS data from their recently completed study, the Shanghai Endometrial Cancer Genetics Study, which comprised 832 endometrial cancer cases and 2,049 controls (1996-2005). Thirty-five SNPs previously associated with obesity or body mass index (BMI; weight (kg)/height (m)(2)) at a minimum significance level of <=5 * 10(-7) in the US National Human Genome Research Institute's GWAS catalog (http://genome.gov/gwastudies) and representing 26 unique loci were evaluated by either direct genotyping or imputation. The authors found that for 22 of the 26 unique loci tested (84.6%), the BMI associated risk variants were present at a higher frequency in cases than in population controls (P = 0.0003). Multiple regression analysis showed that 9 of 35 BMI-associated variants, representing 7 loci, were significantly associated (P <= 0.05) with the risk of endometrial cancer; for all but 1 SNP, the direction of association was consistent with that found for BMI. For consistent SNPs, the allelic odds ratios ranged from 1.15 to 1.29. These 7 loci are in the SEC16B/RASAL, TMEM18, MSRA, SOX6, MTCH2, FTO, and MC4R genes. The associations persisted after adjustment for BMI, suggesting that genetic markers of obesity provide value in addition to BMI in predicting endometrial cancer risk. PMID- 21976112 TI - Design and synthesis of catenated rings based on toroidal DNA structures. AB - Strand proximity and self-crossing that occur intrinsically in the relaxed forms of toroidal DNA are utilized unprecedentedly in our investigations for creating catenated DNA rings. In addition, our current studies show that the geometrical shapes of our newly obtained catenated DNA circles as well as their topological arrangements are vividly visible under atomic force microscopic examination. PMID- 21976113 TI - Single-incision laparoscopic colectomy: technical aspects and short-term results. AB - Single-incision laparoscopic surgery (SILS) is currently regarded as the next major advance in the progress of minimally invasive techniques in colorectal surgery. We describe our initial experience using SILS for the management of colorectal disease and present preliminary short-term results. Between February 2010 and April 2011, 7 patients (4 females and 3 males, mean age 55 years, range 32-74) underwent SILS for either benign or malignant colorectal disease. Preoperative diagnosis was diverticular disease of the sigmoid colon in two patients, malignant polyps of the sigmoid colon in two other patients and large villous tumor of the right colon in three patients. Surgical procedures, 4 anterior resections of the rectum and 3 right hemicolectomies, were performed through a 3 cm single umbilical incision using a SILS multi port device with conventional or articulated laparoscopic instruments. There were no intraoperative complications or conversions in the standard laparoscopic procedure. The mean operative time for anterior resections was 160.0 +/- 10.6 min, whereas it was 160.6 +/- 20 for right hemicolectomies. Blood loss was minimal. No postoperative complications were reported in any of the patients. The overall mean hospital stay was 4.8 +/- 0.2 days (range 4-5). For the subset of patients with malignant or pre-malignant disease, the mean number of retrieved lymph nodes was 15.6 +/- 4.4 (range 6-31). Cosmetic results were considered excellent by all the patients after 15 days. In conclusion, our preliminary experience shows that SILS for colorectal disease is feasible and safe with potential reproducible oncologic results. PMID- 21976114 TI - Dynamic alterations in integrin alpha4 expression by hypoxia are involved in trophoblast invasion during early implantation. AB - Implantation of the blastocyst into the maternal endometrium is mediated by a population of well-differentiated primary cells of the placenta known as trophoblasts, which grow in an invasive and destructive fashion similar to tumor cells. Interactions between the endometrium and trophoblasts are regulated by a coordinated interplay of extracellular matrix (ECM) proteins secreted by the invading extravillous trophoblasts. Integrins act as adhesion receptors and mediate both cell-ECM and cell-cell interactions. However, the correlation between integrin expression and trophoblast invasion under hypoxia is unclear. Here, we analyzed the expression of integrins in HTR-8/SVneo trophoblast cells exposed to hypoxic conditions in order to demonstrate an association between invasion activity and integrin expression in trophoblasts. Trophoblasts were examined by microarray analysis, RT-PCR, western blotting, and zymography after 1% hypoxic treatment, and cell invasion was estimated. The dynamic expression of integrins and human matrix metalloproteinases (MMPs) was observed under hypoxic conditions. The invasiveness of trophoblasts cultured under 1% hypoxic conditions was significantly greater than that of trophoblasts cultured under normoxic conditions through alterations in MMP-2 and -9 (P < 0.05). Notably, integrin alpha4 expression during early hypoxia was negatively regulated by hypoxia inducible factor-1alpha (HIF-1alpha) expression in trophoblasts. The downregulation of integrin alpha4 expression by siRNA treatment controlled trophoblast invasion activity (P < 0.05). Taken together, we suggest that dynamic changes in integrins, including those in integrin alpha4 expression by hypoxia, play a regulatory role in trophoblast invasion. These findings expand our understanding of the potential roles of integrin alpha4 in implantation. PMID- 21976115 TI - Nonfatal traumatic brain injuries related to sports and recreation activities among persons aged <=19 years--United States, 2001-2009. AB - Traumatic brain injuries (TBIs) from participation in sports and recreation activities have received increased public awareness, with many states and the federal government considering or implementing laws directing the response to suspected brain injury. Whereas public health programs promote the many benefits of sports and recreation activities, those benefits are tempered by the risk for injury. During 2001--2005, an estimated 207,830 emergency department (ED) visits for concussions and other TBIs related to sports and recreation activities were reported annually, with 65% of TBIs occurring among children aged 5--18 years. Compared with adults, younger persons are at increased risk for TBIs with increased severity and prolonged recovery. To assess and characterize TBIs from sports and recreation activities among children and adolescents, CDC analyzed data from the National Electronic Injury Surveillance System--All Injury Program (NEISS-AIP) for the period 2001--2009. This report summarizes the results of that analysis, which indicated that an estimated 173,285 persons aged <=19 years were treated in EDs annually for nonfatal TBIs related to sports and recreation activities. From 2001 to 2009, the number of annual TBI-related ED visits increased significantly, from 153,375 to 248,418, with the highest rates among males aged 10--19 years. By increasing awareness of TBI risks from sports and recreation, employing proper technique and protective equipment, and quickly responding to injuries, the incidence, severity, and long-term negative health effects of TBIs among children and adolescents can be reduced. PMID- 21976116 TI - Acute illness and injury from swimming pool disinfectants and other chemicals- United States, 2002-2008. AB - Swimming pools require disinfectants and other chemicals to maintain water quality and prevent swimmers from acquiring infections. When these chemicals are stored or used improperly or when they are handled or applied by persons not using appropriate personal protective equipment (PPE), illness or injury can result. To assess the frequency of illness and injury related to pool chemicals, CDC analyzed data for the period 2002--2008 from six states participating in the Sentinel Event Notification System for Occupational Risk (SENSOR)--Pesticides surveillance program and from the National Electronic Injury Surveillance System (NEISS). This report describes the results of that analysis, which identified 584 cases of illness or injury associated with pool chemicals in the six SENSOR Pesticides states and indicated an estimated national total of 28,071 cases (based on 688 NEISS cases) during that period. For the 77% of state cases and 49% of NEISS cases that had sufficient information to determine factors contributing to illness or injury, the most common contributing factors included mixing incompatible products, spills and splashes of chemicals, lack of appropriate PPE use, and dust clouds or fumes generated by opening a chemical container. Adhering to existing CDC recommendations can prevent some of the reported illnesses and injuries, but additional measures (e.g., improving package design to limit the release of dust clouds and fumes when a container is opened, making containers child-proof, and making product labels easier to understand) might reduce them further. PMID- 21976117 TI - Health plan implementation of U.S. Preventive Services Task Force A and B recommendations--Colorado, 2010. AB - The Patient Protection and Affordable Care Act (PPACA) is aimed at expanding access to health care and lowering cost barriers to seeking and receiving care, particularly high-value preventive care. The legislation requires Medicare and all qualified commercial health plans (except grandfathered individual and employer-sponsored plans) to cover routine preventive services graded A and B by the U.S. Preventive Services Task Force (USPSTF) at no cost to the consumer, along with recommended immunizations and additional preventive care and screenings for women. In 2009, Colorado passed a law with similar USPTF A and B service coverage requirements. To determine how Colorado health plans had interpreted the state and federal law, the Colorado Department of Public Health and Environment (CDPHE) interviewed representatives of commercial health plans serving Colorado residents. The results of those interviews indicated that different health plans interpreted certain USPSTF recommendations differently, including tobacco screening and pharmacotherapy, colorectal cancer screening, and obesity screening and counseling. One health plan communicated the scope, eligibility criteria, and content of the new preventive services coverage to its members or providers. The differences in interpretation of the USPSTF recommendations and limited communication to consumers or health-care providers in Colorado might be repeated in other states. To ensure optimal consumer and health-care provider utilization of preventive service benefits, the preventive services supported by USPSTF A and B recommendations should be clearly defined in health plan benefit language, with processes put in place for consistent implementation and eligibility criteria communicated to both consumers and providers. The experience in Colorado shows that public health organizations can play a key role in successfully implementing PPACA prevention services provisions. PMID- 21976118 TI - Vital signs: alcohol-impaired driving among adults--United States, 2010. AB - BACKGROUND: Alcohol-impaired driving crashes account for nearly 11,000 crash fatalities, or about one third of all crash fatalities in the United States. METHODS: CDC analyzed data from the 2010 Behavioral Risk Factor Surveillance System survey to obtain the prevalence, episodes, and rates of alcohol-impaired driving (defined as driving "when you've had perhaps too much to drink" in the past 30 days) among U.S. adults aged >=18 years who responded to the survey by landline telephone. RESULTS: In 2010, an estimated 4 million U.S. adult respondents reported at least one episode of alcohol-impaired driving, for an estimated total of approximately 112 million alcohol-impaired driving episodes or 479 episodes per 1,000 adult population. From a peak in 2006, such episodes decreased 30% through 2010. Men accounted for 81% of all episodes with young men aged 21--34 years accounting for 32% of all episodes. Additionally, 85% of alcohol-impaired driving episodes were reported by persons who also reported binge drinking, and the 4.5% of the adult population who reported binge drinking at least four times per month accounted for 55% of all alcohol-impaired driving episodes. Episode rates were nearly four times higher among persons who reported not always wearing seatbelts compared with persons who reported always wearing seatbelts. CONCLUSIONS: Rates of self-reported alcohol-impaired driving have declined substantially in recent years. However, rates remain disproportionally high among young men, binge drinkers, and those who do not always wear a seat belt. IMPLICATIONS FOR PUBLIC HEALTH: States and communities should continue current evidence-based strategies, such as sobriety checkpoints and enforcement of 0.08 g/dL blood alcohol concentration laws to deter the public from driving while impaired. Additionally, all states should consider requiring ignition interlocks on the vehicles of all persons convicted of alcohol-impaired driving. States without primary seatbelt laws should consider enacting them to reduce fatalities in alcohol-impaired driving crashes. PMID- 21976119 TI - Multistate outbreak of listeriosis associated with Jensen Farms cantaloupe- United States, August-September 2011. AB - Listeriosis is caused by Listeria monocytogenes, a gram-positive bacillus common in the environment and acquired by humans primarily through consumption of contaminated food. Infection causes a spectrum of illness, ranging from febrile gastroenteritis to invasive disease, including sepsis and meningoencephalitis. Invasive listeriosis occurs predominantly in older adults and persons with impaired immune systems. Listeriosis in pregnant women is typically a mild "flu like" illness, but can result in fetal loss, premature labor, or neonatal infection. Listeriosis is treated with antibiotics. On September 2, 2011, the Colorado Department of Public Health and Environment (CDPHE) notified CDC of seven cases of listeriosis reported since August 28. On average, Colorado reports two cases of listeriosis annually in August. By September 6, all seven Colorado patients interviewed with the Listeria Initiative* questionnaire reported eating cantaloupe in the month before illness began, and three reported eating cantaloupe marketed as "Rocky Ford." PMID- 21976120 TI - [Recurrence prevention of urolithiasis with respect to economic aspects]. AB - Recurrence prevention in urinary stone disease not only makes good medical but also economic sense. Up to 40% of recurrences can be prevented by a rational urinary stone metaphylaxis whereby not only treatment costs but also the cost of lost productive work time can be saved. Detailed knowledge of stone composition and medical history of the patient is a prerequisite for a rational metaphylaxis which according to the S2 guidelines results in assignment to the high or low risk group. The required diagnostic and therapeutic measures are also decided by this classification. In addition to general metaphylaxis (reduction of overweight, physical activity, appropriate fluid intake, balanced diet) further specific measures may be necessary depending on the risk group and stone type. PMID- 21976123 TI - [Interview with Professor Dr. Michael Sohn (interview by the Pressestelle der DGU)]]. PMID- 21976121 TI - [Third-line therapy for metastasized renal cell carcinoma: a randomized, multicenter non-blinded phase III study to compare safety and effectiveness of TF1258 versus sorafenib in patients with metastasized renal cell carcinoma following failure of antiangiogenic (VEGF targeted and mTOR inhibition) therapy (GOLD-AN 31/11 of the Working Group Urological Oncology)]. PMID- 21976124 TI - [Karlsruhe allows more advertising for physicians]. PMID- 21976125 TI - ["Specialists don't work enough"!]. PMID- 21976127 TI - Antibacterial and anti-inflammatory activity of traditional Chinese herb pairs, Angelica sinensis and Sophora flavescens. AB - The purpose of the present study was to investigate the antibacterial and anti inflammatory activity of Angelica sinensis extract (AE), Sophora flavescens extract (SE), and herb pair A. sinensis and S. flavescens extract (HPE). Endotoxin-induced uveitis (EIU) was induced in rats by a footpad injection of lipopolysaccharide. The anti-inflammatory potential of AE, SE, and HPE in the regulation of nuclear factor kappa B (NF-kappaB), maleic dialdehyde (MDA), polymorphonuclear cells (PMN), interleukin-1beta (IL-1beta), inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha), adhesion molecule (ICAM-1), and cyclooxygenase-2 (COX-2) was determined by ELISA and immunohistochemistry. HPE showed strong antibacterial activity at all tested concentrations (1.25, 2.5, and 5 MUg/ml) to Escherichia coli, Staphylococcus aureus, and Shigella Castellani and Chalmers. HPE significantly inhibited EIU induced upregulation of NF-kappaB activation and the production of IL-1beta, TNF alpha, iNOS, ICAM-1, and COX-2. Moreover, HPE suppressed MDA and infiltration of PMN. The study supports the hypothesis that the antipimple and anti-eczema activities of Dangguikushen compound recipe are attributed to herb pairs, A. sinensis and S. flavescens, used in combination. PMID- 21976128 TI - Barrier protective activities of phloroglucinol on lipopolysaccharide (LPS) induced barrier disruption in human endothelial cells. AB - Phloroglucinol plays an important role in oxidative stress, inflammatory responses, and matrix metalloproteinase (MMP) regulation. However, the barrier protective functions of phloroglucinol are not well studied. The objective of this study was to fill this gap. We did this by investigating the barrier protective activities of phloroglucinol on lipopolysaccharide (LPS)-induced barrier disruption in human endothelial cells measured by cellular permeability, monocytes adhesion, and migration toward human endothelial cells. The results showed that phloroglucinol inhibited LPS-induced barrier hyperpermeability, monocyte adhesion, and migration. These inhibitory effects were significantly correlated with the inhibitory functions of phloroglucinol on LPS-induced cell adhesion molecules. Furthermore, LPS-induced nuclear factor-kappaB (NF-kappaB) and tumor necrosis factor-kappaB (TNF-kappaB) release from human umbilical vein endothelial cells (HUVECs) was inhibited by phloroglucinol. Given these results, phloroglucinol could be a candidate as a therapeutic agent for various systemic inflammatory diseases. PMID- 21976129 TI - Update on the Management of Acute Decompensated Heart Failure. AB - OPINION STATEMENT: Treatment goals of acute decompensated heart failure are to decrease congestion, afterload, and neurohormonal activation in order to improve hemodynamics and symptoms and, perhaps, reduce in-hospital events, re hospitalizations, and mortality while avoiding toxicities of therapy such as hypotension, arrhythmias, and renal dysfunction. Relief of congestion through intravenous loop diuretics is a mainstay of therapy. In cases where diuretics are not effective, ultrafiltration may be used to achieve euvolemia. Beta-blockers should be continued or reduced in dose at admission but should not typically be held. In patients with normotensive or hypertensive heart failure, afterload reduction with vasodilators should be instituted at presentation. Choice of a particular agent such as nitroglycerin, nitroprusside, or nesiritide depends on patient characteristics such as presence of ischemia, degree of congestion, and renal function. Nitroprusside may be preferable in patients with congestion and low cardiac output, but with caution in patients with significant hypotension. Intravenous inotropes/inodilators, such as dobutamine and milrinone, should be limited to hypotensive patients with evidence of poor tissue perfusion. Milrinone may be preferable in patients who have significant pulmonary venous hypertension. In patients who do not respond to initial medical therapy and who are candidates for either cardiac transplantation or destination left ventricular assist device, mechanical circulatory support should be considered early, prior to the development of end-organ damage. PMID- 21976130 TI - Synthesis of d-f coordination polymer nanoparticles and their application in phosphorescence and magnetic resonance imaging. AB - Magneto-phosphorescent d-f coordination polymer nanoparticles (f-CPPs) were conveniently synthesized by phosphorescent carboxyl-functionalized iridium complexes as building blocks and magnetic Gd(III) ions as metallic nodes. They reveal uniform hollow spheres with an average diameter of around 60 nm and wall thickness of about 10 nm. Water soluble f-CPPs were obtained by polyvinylpyrolidone modification (denoted as f-CPPs@PVP), which had an intense red phosphorescence, moderate longitudinal relaxivity (r(1)) and low cytotoxicity. Furthermore, inductively coupled plasma atomic emission spectroscopy (ICP-AES) and confocal laser scanning microscopy (CLSM) confirmed f CPPs@PVP could be taken up by living cells effectively. Therefore, they should be a novel nano-bioprobe for the multimodal imaging of cancer cells. PMID- 21976131 TI - An alternative linear trend analysis for assessing the results of the mouse lymphoma assay. AB - As recommended by the mouse lymphoma assay (MLA) Workgroup of the International Workshop on Genotoxicity Testing (Aberdeen, 2003), a trend test is critical if an induced mutant frequency (MF) of at least 126 * 10(-6) (global evaluation factor, GEF) is achieved at one or more test concentrations. Only those responses that both achieve the GEF and a significant trend are biologically relevant. While no specific trend test was recommended by the Workshop, a trend test was recommended by the UK Environmental Mutagen Society (1989). The test uses MF (untransformed) averaged over replicate cultures following a consistency test (against a historical heterogeneity factor) in a weighted linear regression with chi-square (chi(2)) test for slope and returns significant results in virtually all cases that are positive for the GEF, including those with no apparent dose-response. We have explored an alternative method where the natural logarithm of MF and its variance are estimated for each replicate culture separately and used in a weighted ordinary linear regression with t-test for slope. Using test cases positive for the GEF, the P-value from this model is shown to be sensitive to changes in the number of replicates, the shape and magnitude of mutant induction, in contrast to the chi(2) model. Cases with no apparent dose-response and thereby questionable biological significance are tested negative by our method but positive by the chi(2) model. Our method is thus straight-forward and provides a meaningful complement to the GEF in assessing the biological significance of the MLA results. PMID- 21976132 TI - Dasatinib combined with docetaxel for castration-resistant prostate cancer: results from a phase 1-2 study. AB - BACKGROUND: To determine the potential efficacy of targeting both the tumor and bone microenvironment in patients with castration-resistant prostate cancer (PC), the authors conducted a phase 1-2 trial combining docetaxel with dasatinib, an oral SRC inhibitor. METHODS: In phase 1, 16 men received dasatinib 50 to 120 mg once daily and docetaxel 60 to 75 mg/m(2) every 21 days. In phase 2, 30 additional men received dasatinib 100 mg once daily/docetaxel 75 mg/m(2) every 21 days. Efficacy endpoints included changes in prostate-specific antigen (PSA), measurable disease, bone scans, and markers of bone metabolism. Safety and pharmacokinetics were also studied. RESULTS: Combination dasatinib and docetaxel therapy was generally well tolerated. Thirteen of 46 patients (28%) had a grade 3 4 toxicity. Drug-drug interactions and a maximum tolerated dose were not identified. Durable 50% PSA declines occurred in 26 of 46 patients (57%). Of 30 patients with measurable disease, 18 (60%) had a partial response. Fourteen patients (30%) had disappearance of a lesion on bone scan. In bone marker assessments, 33 of 38 (87%) and 26 of 34 (76%) had decreases in urinary N telopeptide or bone-specific alkaline phosphatase levels, respectively. Twenty eight patients (61%) received single-agent dasatinib after docetaxel discontinuation and had stabilization of disease for an additional 1 to 12 months. CONCLUSIONS: The high objective response rate and favorable toxicity profile are promising and justify randomized studies of docetaxel and dasatinib in castration-resistant PC. Parallel declines in levels of PSA and bone markers are consistent with cotargeting of epithelial and bone compartments of the cancer. Treatment with single-agent dasatinib following docetaxel cessation warrants further study. Cancer 2012;. (c) 2011 American Cancer Society. PMID- 21976133 TI - Usefulness of miriplatin as an anticancer agent for transcatheter arterial chemoembolization in patients with unresectable hepatocellular carcinoma. AB - BACKGROUND: Injection of a suspension of miriplatin into the hepatic artery has been employed for the treatment of hepatocellular carcinoma (HCC). The efficacy and safety of transcatheter arterial chemoembolization (TACE) using miriplatin were evaluated. METHODS: A total of 236 patients with unresectable HCC received miriplatin administration through the hepatic artery, followed by embolization with porous gelatin particles. The efficacy of this treatment modality was evaluated by contrast-enhanced computed tomography performed 1 month later and its safety based on the Common Terminology Criteria for Adverse Events (CTCAE). RESULTS: Miriplatin was used at a median dose of 66 mg. The therapeutic efficacy was evaluated in 130 patients, and the overall and complete response rates were 70.0 and 37.7%, respectively. The efficacies differed depending on the staging and Japan integrated staging (JIS) scores of the HCCs, with the overall and complete response rates being 87.7 and 66.7% for stage I and stage II HCC, and 56.2 and 15.1% for stage III and stage IV HCC, respectively; the corresponding rates were 93.2 and 70.5%, respectively, for HCCs with score 0 and score 1, and 58.1 and 20.9%, respectively, for those with scores 2-4. The stage of HCC was a significant independent factor associated with curative effects of TACE using miriplatin. Grade 3 elevation of serum transaminase levels was found in 23.4% of the patients; however, the values returned to the baseline levels. CONCLUSIONS: Miriplatin is a useful and safe agent for TACE in patients with HCC stage I or II and/or JIS score 0 or 1 only when radiofrequency ablation and liver resection cannot be performed. PMID- 21976134 TI - Serum gamma-glutamyltransferase level is associated with serum superoxide dismutase activity and metabolic syndrome in a Japanese population. AB - BACKGROUND: Serum gamma-glutamyltransferase level has attracted considerable attention as a predictor of various conditions, such as cardiovascular disease and cancer. Although the mechanism that links the serum gamma-glutamyltransferase level to these diseases is not fully understood, one explanation is that gamma glutamyltransferase may be closely related to oxidative stress. We conducted a large cross-sectional study to evaluate the relationship between serum gamma glutamyltransferase and oxidative stress. METHODS: We examined anti-oxidative stress activity and accumulation of oxidative stress in serum obtained from 2907 subjects who underwent a complete health check-up. We used serum total superoxide dismutase activity as an index of anti-oxidative stress activity. Superoxide dismutase is one of the most important intracellular and extracellular defense systems against superoxide, but the relationship between serum superoxide dismutase activity and the serum gamma-glutamyltransferase level is unclear. RESULTS: The serum gamma-glutamyltransferase level was negatively correlated with serum superoxide dismutase activity, a correlation that was observed even within the normal range. A subgroup analysis stratified by the amount of alcohol consumed also showed a similar correlation. In contrast, the serum gamma glutamyltransferase level was positively correlated with serum lipid peroxide level, even in the normal range. Furthermore, an increased serum gamma glutamyltransferase level was significantly associated with the progression of metabolic syndrome and carotid artery intima-media thickness. CONCLUSIONS: The serum gamma-glutamyltransferase level, even in the normal range, was significantly associated with anti-oxidative stress activity, the accumulation of oxidative stress, metabolic syndrome, and atherosclerosis. Measuring the serum gamma-glutamyltransferase level is simple and inexpensive, and this level can be used as a sensitive marker of oxidative stress and metabolic syndrome. PMID- 21976135 TI - Modification of the cranial closing wedge ostectomy technique for the treatment of canine cruciate disease. Description and comparison with standard technique. AB - OBJECTIVE: To describe a modification of the cranial closing wedge ostectomy (CCWO) technique and to compare its efficacy to the standard technique on cadaveric specimens. METHODS: The standard and modified CCWO technique were applied to eight pairs of cadaveric tibiae. The following parameters were compared following the ostectomy: degrees of plateau levelling achieved (degrees), tibial long axis shift (degrees), reduction in tibial length (mm), area of bone wedge removed (cm2), and the area of proximal fragment (cm2). RESULTS: The size of the removed wedge of bone and the reduction in tibial length were significantly less with the modified CCWO technique. CLINICAL SIGNIFICANCE: The modified CCWO has two main advantages. Firstly a smaller wedge is removed, allowing a greater preservation of bone stock in the proximal tibia, which is advantageous for implant placement. Secondly, the tibia is shortened to a lesser degree, which might reduce the risk of recurvatum, fibular fracture and patella desmitis. These factors are particularly propitious for the application of this technique to Terrier breeds with excessive tibial plateau angle, where large angular corrections are required. The modified CCWO is equally effective for plateau levelling and results in an equivalent tibial long-axis shift. A disadvantage with the modified technique is that not all of the cross sectional area of the distal fragment contributes to load sharing at the osteotomy. PMID- 21976136 TI - Osmotic release of bioactive VEGF from biodegradable elastomer monoliths is the same in vivo as in vitro. AB - The feasibility of generating an extended period of linear release of therapeutic proteins from photo-cross-linked, biodegradable elastomer monolithic devices in vitro has been previously demonstrated. The release is driven primarily by the osmotic pressure generated upon the dissolution of the encapsulated particles within the polymer. The osmotic pressure is provided by co-incorporation into the particle of trehalose as an osmotigen. Herein, we demonstrate that the release rate of a therapeutic protein, vascular endothelial growth factor (VEGF), by this osmotic pressure mechanism is the same in vivo as found in vitro. (125) I-VEGF was colyophilized with trehalose and serum albumin and distributed as particles throughout a photo-cross-linked elastomer composed of trimethylene carbonate, epsilon-caprolactone, and d,l-lactide. The release of VEGF from the device was monitored by measuring the decrease in radioactivity within the devices in vitro and within explanted devices that had been implanted subcutaneously in the dorsal area of Wistar rats. The released VEGF remained bioactive in vivo, inducing the formation of blood vessels that contained red blood cells. Furthermore, the released trehalose was well tolerated by the surrounding tissue. PMID- 21976137 TI - Targeting of hepatocellular carcinoma with glypican-3-targeting peptide ligand. AB - Hepatocellular carcinoma is a common malignancy. The carcinoma cells express glypican-3 (GPC-3) on the cell membrane. GPC-3 is also expressed in melanoma cells. Therefore, GPC-3 might be a potential target for tumor imaging or therapy. Here, proteomic mass spectrometry was used to identify peptides that target GPC-3 expressing tumors. A mammalian expression vector expressing a FLAG-GPC-3 fusion protein was cloned for immunoprecipitation. With the use of liposomes, the vector was transfected into HepG2 (HepG2/FLAG-GPC-3) and HEK 293 cells, and the transfected cell lines were selected with geneticin. HepG2/FLAG-GPC-3 cells were used for immunoprecipitation of FLAG-GPC-3 fusion protein. Seven peptide candidates (L1-L7) were selected for GPC-3-targeting ligands by mass spectrometric analysis. The L5 peptide with 14 amino acids (Arg-Leu-Asn-Val-Gly Gly-Thr-Tyr-Phe-Leu-Thr-Thr-Arg-Gln) showed selective binding to the GPC-3 expressing tumor cells, as did a shortened L5 peptide (L5-2) with seven amino acids (Tyr-Phe-Leu-Thr-Thr-Arg-Gln). These peptide ligands have potential as targeting moieties to GPC-3-expressing tumors for diagnostic and/or therapeutic purposes. PMID- 21976139 TI - Further evidence that the expression of CD38 and HLA-DR(+) in CD8(+) lymphocytes does not correlate to disease progression in HIV-1 vertically infected children. AB - BACKGROUND: In adults, an increase in CD8(+)CD38(+) T cell levels is a strong indicator of disease progression in HIV infection. However, in children, data are conflicting. Slow-progressing children (SPC) provide an exceptional resource for the investigation and clarification of the immunological and virological mechanisms of natural control of HIV infection and can be used to investigate prognostic indicators of disease progression. OBJECTIVES: To investigate the immune activation status and T regulatory (Treg) cell levels in SPC. STUDY DESIGN: A cross-sectional study was carried out on 28 children 8 years old and older who were vertically infected with HIV. The children were stratified into 3 groups according to their clinical outcome: SPC (anti-retroviral-therapy-naive; >=8 years-old; CD4 >=20%; viral load <25,000 copies), IF/VF (anti-retroviral therapy but with no therapeutic response), and IS/VS (anti-retroviral therapy with good therapeutic response). Uninfected children (NI) were assessed as healthy control group. RESULTS: A higher percentage of activated CD8(+) T cells were found in all HIV infected children, regardless of the evolution of disease. The activation of CD8(+) T cells was not associated with either viral load or the percentage of CD4(+) T cells. In addition, Treg cell levels did not show any correlation with the clinical outcome or the activation status of CD8(+) T cells. CONCLUSIONS: HIV-1-infected children presented an increased percentage of activated CD8(+) T cells and an unaltered percentage of Treg cells, regardless of their clinical evolution. Thus, these immunological parameters should not be used for prognostic evaluation. PMID- 21976138 TI - Human pluripotent stem cell therapy for Huntington's disease: technical, immunological, and safety challenges human pluripotent stem cell therapy for Huntington's disease: technical, immunological, and safety challenges. AB - Intra-striatal transplantation of homotypic fetal tissue at the time of peak striatal neurogenesis can provide some functional benefit to patients suffering from Huntington's disease. Currently, the only approach shown to slow down the course of this condition is replacement of the neurons primarily targeted in this disorder, although it has been transient and has only worked with a limited number of patients. Otherwise, this dominantly inherited neurodegenerative disease inevitably results in the progressive decline of motricity, cognition, and behavior, and leads to death within 15 to 20 years of onset. However, fetal neural cell therapy of Huntington's disease, as with a similar approach in Parkinson's disease, is marred with both technical and biological hurdles related to the source of grafting material. This heavily restricts the number of patients who can be treated. A substitute cell source is therefore needed, but must perform at least as well as fetal neural graft in terms of brain recovery and reconstruction, while overcoming its major obstacles. Human pluripotent stem cells (embryonic in origin or induced from adult cells through genetic reprogramming) have the potential to meet those challenges. In this review, the therapeutic potential in view of 4 major issues is identified during fetal cell therapy clinical trials: 1) logistics of graft procurement, 2) quality control of the cell preparation, 3) immunogenicity of the graft, and 4) safety of the procedure. PMID- 21976141 TI - Notch2-induced COX-2 expression enhancing gastric cancer progression. AB - Gastric carcinoma is one of the most common and mortal types of malignancy worldwide. To date, the mechanisms controlling its aggressiveness are not yet fully understood. Notch signal pathway can function as either an oncogene or a tumor suppressor in tumorigenesis. Four members (Notch1-4) of Notch receptors were found in mammals and each exhibits distinct roles in tumor progression. Previous study showed that the activated Notch1 receptor promoted gastric cancer progression through cyclooxygenase-2 (COX-2). This study addressed whether Notch2 signal pathway is also involved in gastric cancer progression. Constitutive expression of Notch2 intracellular domain (N2IC), the activated form of Notch2 receptor, promoted both cell proliferation and xenografted tumor growth of human stomach adenocarcinoma SC-M1 cells. The colony formation, migration, invasion, and wound-healing abilities of SC-M1 cells were enhanced by N2IC expression, whereas these abilities were suppressed by Notch2 knockdown. Similarly, Notch2 knockdown inhibited cancer progressions of AGS and AZ521 gastric cancer cells. Expression of N2IC also caused epithelial-mesenchymal transition in SC-M1 cells. Furthermore, N2IC bound to COX-2 promoter and induced COX-2 expression through a CBF1-dependent manner in SC-M1 cells. The ability of N2IC to enhance tumor progression in SC-M1 cells was suppressed by knockdown of COX-2 or treatment with NS-398, a COX-2 inhibitor. Moreover, the suppression of tumor progression by Notch2 knockdown in SC-M1 cells was reversed by exogenous COX-2 or its major enzymatic product PGE(2) . Taken together, this study is the first to demonstrate that the Notch2-COX-2 signaling axis plays an important role in controlling gastric cancer progression. PMID- 21976140 TI - Involvement of tissue bacteria in the onset of diabetes in humans: evidence for a concept. AB - AIMS/HYPOTHESIS: Evidence suggests that bacterial components in blood could play an early role in events leading to diabetes. To test this hypothesis, we studied the capacity of a broadly specific bacterial marker (16S rDNA) to predict the onset of diabetes and obesity in a general population. METHODS: Data from an Epidemiological Study on the Insulin Resistance Syndrome (D.E.S.I.R.) is a longitudinal study with the primary aim of describing the history of the metabolic syndrome. The 16S rDNA concentration was measured in blood at baseline and its relationship with incident diabetes and obesity over 9 years of follow-up was assessed. In addition, in a nested case-control study in which participants later developed diabetes, bacterial phylotypes present in blood were identified by pyrosequencing of the overall 16S rDNA gene content. RESULTS: We analysed 3,280 participants without diabetes or obesity at baseline. The 16S rDNA concentration was higher in those destined to have diabetes. No difference was observed regarding obesity. However, the 16S rDNA concentration was higher in those who had abdominal adiposity at the end of follow-up. The adjusted OR (95% CIs) for incident diabetes and for abdominal adiposity were 1.35 (1.11, 1.60), p = 0.002 and 1.18 (1.03, 1.34), p = 0.01, respectively. Moreover, pyrosequencing analyses showed that participants destined to have diabetes and the controls shared a core blood microbiota, mostly composed of the Proteobacteria phylum (85 90%). CONCLUSIONS/INTERPRETATION: 16S rDNA was shown to be an independent marker of the risk of diabetes. These findings are evidence for the concept that tissue bacteria are involved in the onset of diabetes in humans. PMID- 21976142 TI - Effects of dimethylsulfoxide on behavior and antioxidant enzymes response of planarian Dugesia japonica. AB - In this study, the toxicity, behavioral and antioxidant activity effects of dimethylsulfoxide (DMSO) on planarian Dugesia japonica were investigated. The results showed that the mortality was directly proportional to the DMSO concentration, and planarian locomotor velocity decreased as the concentration of DMSO increased. The recovery of the motility for planarians pre-exposed to DMSO was found to be time- and dose-dependent, and only those pre-exposed to 0.1-3% DMSO resulted in full recovery. The antioxidant enzymes of planarians in response to long-term DMSO stress was also altered in a time- and dose-dependent manner. Planarians revealed more tolerance to DMSO toxicity at low DMSO (0.1%) level in short- and long-term DMSO stress, in which an efficient antioxidant system was involved and the motility was not affected. PMID- 21976143 TI - Dimethoate-induced oxidative damage in erythrocytes of female adult rats: possible protective effect of vitamin E and selenium supplemented to diet. AB - Pesticide hazards have been accentuated by the sharp rise in their agricultural, industrial and domestic use. Acute exposure to pesticides can cause oxidative damage. Our study investigated the potential ability of selenium (Se) and/or vitamin E, used as nutritional supplements, to alleviate erythrocyte oxidative damage induced by dimethoate (DM), an organophosphate pesticide. Female Wistar rats were exposed to DM (0.2g/L(-1) of drinking water), DM + Se (0.5 mg/kg of diet), DM + vitamin E (100 mg/kg of diet), or DM + Se + vitamin E. Rats exposed to DM for 30 days showed an increase in malondialdehyde levels, superoxide dismutase and glutathione peroxidase activities in their erythocytes, while Na(+),K(+)-ATPase and catalase activities, glutathione, non-protein thiol, vitamin E and vitamin C levels decreased. We also noted an increase in lactate dehydrogenase activity, marker of haemolysis and a decrease in acetylcholinesterase, the principal mode of organophosphorus action. Co administration of Se or vitamin E to the diet of DM-treated rats ameliorated the biochemical parameters cited above. But the combined effect of Se and vitamin E was more powerful in antagonizing DM-induced oxidative stress. Therefore, our investigation revealed that both Se and vitamin E were useful elements in preventing DM-induced erythrocytes damage. PMID- 21976145 TI - A case study in ultracold reactive scattering: D + H2. AB - We report theoretical results for reaction and vibrational quenching of the ultracold collision D + H(2) (v, j = 0) for a wide range of initial vibrationally excited states v. The v-dependence of the zero-temperature limit of the reaction rate coefficient shows two distinct regimes: a barrier dominated regime for 0 <= v <= 4, and a barrierless regime for v >= 5. We also present detailed distributions over the rovibrational states of the products. We find an approximate conservation of the internal vibrational energy; namely, the branching ratios always favor the highly excited final states, which have vibrational energies similar to that of the entrance channel. PMID- 21976144 TI - A systems biology approach to identify molecular pathways altered by HDAC inhibition in osteosarcoma. AB - Osteosarcoma (OS) is the most common primary tumor in humans and dogs affecting the skeleton, and spontaneously occurring OS in dogs serves as an extremely useful model. Unacceptable toxicities using current treatment protocols prevent further dose-intensification from being a viable option to improve patient survival and thus, novel treatment strategies must be developed. Histone deacetylase inhibitors (HDACi) have recently emerged as a promising class of therapeutics demonstrating an ability to enhance the anti-tumor activity of traditional chemotherapeutics. To date, gene expression analysis of OS cell lines treated with HDACi has not been reported, and evaluation of the resultant gene expression changes may provide insight into the mechanisms that lead to success of HDACi. Canine OS cells, treated with a clinically relevant concentration of the HDACi valproic acid (VPA), were used for expression analysis on the Affymetrix canine v2.0 genechip. Differentially expressed genes were grouped into pathways based upon functional annotation; pathway analysis was performed with MetaCore and Ingenuity Pathways Analysis software. Validation of microarray results was performed by a combination of qRT-PCR and functional/biochemical assays revealing oxidative phosphorylation, cytoskeleton remodeling, cell cycle, and ubiquitin-proteasome among those pathways most affected by HDACi. The mitomycin C-bioactivating enzyme NQ01 also demonstrated upregulation following VPA treatment, leading to synergistic reductions in cell viability. These results provide a better understanding of the mechanisms by which HDACi exert their effect in OS, and have the potential to identify biomarkers that may serve as novel targets and/or predictors of response to HDACi-containing combination therapies in OS. PMID- 21976146 TI - Patient and surgeon characteristics associated with primary anterior cruciate ligament reconstruction graft selection. AB - BACKGROUND: It has been suggested that a surgeon's experience and training are the most important factors associated with graft selection, but no studies have qualified this association. Graft usage prevalence has not been described for large anterior cruciate ligament reconstruction (ACLR) populations in the United States. PURPOSE: To describe the prevalence of graft usage in a large community based practice and evaluate the association of patient, surgeon, and site characteristics with choice of primary ACLR graft. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Primary ACLRs performed between February 2005 and June 2010 were selected for the study. A community-based ligament registry was used to identify cases and variables used for analysis. Graft choice (any allograft, hamstring autograft, and bone-patellar tendon-bone [BPTB] autograft) was compared by patient characteristics and surgeon and site characteristics. Associations between independent variables and graft choice were evaluated using a polychotomous regression model. RESULTS: Of the 9849 patients included in the study, 64% were male, and overall median age was 28 years. Of these, 2796 (28.4%) received BPTB autografts, 3013 (30.6%) received hamstring autografts, and 4040 (41.0%) received allografts. The prevalence of graft source by patients' gender, race, age, body mass index (BMI), as well as surgeons' fellowship training status, average volume, and site volume were significantly different (all P < .001). Adjusted models showed that patients' gender (P < .001), race (P = .018), age (P < .001), BMI (P < .001), as well as surgeons' fellowship training status (P < .001), average volume (P < .001), and site volume (P < .001) are associated with graft selection. Older and female patients with lower BMI were more likely to receive allografts and hamstring autografts than BPTB autografts. Cases performed by non-fellowship-trained surgeons, lower volume sites, and/or lower volume surgeons were also more likely to be performed with allografts or hamstring autografts than BPTB autografts. CONCLUSION: Gender, age, race, as well as facility and surgeon characteristics such as volume and location are associated with ACL graft choices. PMID- 21976149 TI - An apolipophorin III protein from the hemolymph of desert locust, Schistocerca gregaria. AB - Apolipophorin III (apoLp-III) from insects and apolipoprotein A-I from humans, are major component of the lipoprotein and share various properties. ApoLp-III is an abundant hemolymph protein. Besides its crucial role in lipid transport, apoLp III is able to associate with fungal and bacterial membranes and stimulate cellular immune responses. ApoLp-III was isolated and purified from the hemolymph of desert locust Schistocerca gregaria by ion-exchange and reversed-phase chromatography. The purity and the molecular weight of apoLp-III were determined at ~19,000 Da by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. According to similarities in the amino terminal sequence, molar mass and retention on reversed-phase analytical HPLC column, this protein is a Schistocerca gregaria homologue of Locusta migratoria apoLp-III. PMID- 21976150 TI - Study on the pyrolysis of cellulose for bio-oil with mesoporous molecular sieve catalysts. AB - Mesoporous materials possess a hexagonal array of uniform mesopores, high surface areas, and moderate acidity. They are one of the important catalysts in the field of catalytic pyrolysis. In this paper, mesoporous materials of Al-MCM-41, La-Al MCM-41, and Ce-Al-MCM-41 were synthesized, characterized, and tested as catalysts in the cellulose catalytic pyrolysis process using a fixed bed pyrolysis reactor. The results showed that mesoporous materials exhibited a strong influence on the pyrolytic behavior of cellulose. The presence of these mesoporous molecular sieve catalysts could vary the yield of products, which was that they could decrease the yield of liquid and char and increase the yield of gas product, and could promote high-carbon chain compounds to break into low-carbon chain compounds. Mesoporous molecular sieve catalysts were benefit to the reaction of dehydrogenation and deoxidation and the breakdown of carbon chain. Further, La-Al MCM-41 and Ce-Al-MCM-41 catalysts can produce more toluene and 2-methoxy-phenol, as compared to the non-catalytic runs. PMID- 21976147 TI - The prevalence of common CFTR mutations in Iranian infertile men with non-CAVD obstructive azoospermia by using ARMS PCR techniques. AB - PURPOSE: To evaluate five common cystic fibrosis trans-membrane conductance regulator (CFTR) mutations (DeltaF508, G542X, R117H, W1282X and N1303K) in the Iranian infertile men with noncongenital absence of vas deferens (CAVD) obstructive azoospermia. METHODS: The common CFTR gene mutations were tested on blood samples from 53 infertile men with non-CAVD obstructive azoospermia and 50 normal men as control individuals. Genomic DNA is extracted from the whole blood and the common CFTR mutations have been detected by the amplification refractory mutation system (ARMS) techniques. RESULTS: The common CFTR mutations were found positive in 5/53)9.43%(for DeltaF508 and 4/53)7.55%(for G542X mutation of all patients tested. Also, no CFTR mutations were detected in the normal men. CONCLUSION: The common CFTR mutations were detected in 9/53(17%) infertile men with non-CAVD obstructive azoospermia. Pre-treatment CFTR mutation analysis remains critical to distinguish cystic fibrosis (CF) genotypes for men with non CAVD obstructive azoospermia. PMID- 21976151 TI - Solvent-Free Production of Bioflavors by Enzymatic Esterification of Citronella (Cymbopogon winterianus) Essential Oil. AB - Enzymatic esterification of citronella essential oil towards the production of geranyl and citronellyl esters may present great scientific and technological interest due to the well-known drawbacks of the chemical-catalyzed route. In this context, this work reports the maximization of geranyl and citronellyl esters production by esterification of oleic and propionic acids in a solvent-free system using a commercial immobilized lipase as catalyst. Results of the reactions showed that the strategy adopted for the experimental design proved to be useful in evaluating the effects of the studied variables on the reaction conversion using Novozym 435 as catalyst. The operating conditions that maximized the production of each ester were determined, leading, in a general way, to conversions of about 90% for all systems. New experimental data on enzymatic esterification of crude citronella essential oil for geranyl and citronellyl esters production in solvent-free system are reported in this work. PMID- 21976152 TI - Influence of the compound selection process on the performance of human clearance prediction methods. AB - This is a commentary on the series of five manuscripts written as part of the Pharmaceutical Research and Manufacturers of America Clinical and Preclinical Development Committee initiative on predictive models of human pharmacokinetics (PK). In particular, we wish to comment on the third paper in the series, which describes the performance of prediction methods of human clearance (CL). Human CL prediction methods described in the third manuscript are fundamental to the work presented in manuscripts four and five on the prediction of human PK profiles. In this commentary, we examine the influence of the compound selection process by performing a probability analysis and examining the CL properties of compounds that are selected using an idealized drug discovery screening process focused on PK optimization. The results of the analysis suggest that the selection of screening species can influence the performance of various predictive models of human CL. PMID- 21976154 TI - Need and potential value of the Pig-ain vivo mutation assay-a HESI perspective. AB - The Health and Environmental Sciences Institute (HESI), a global branch of the International Life Sciences Institute (ILSI), initiated a project committee entitled "Relevance and Follow-up of Positive Results from In Vitro Genetic Toxicity Testing (IVGT)" with the overall objective of improving the scientific basis for the interpretation of results from genetic toxicology testing. The IVGT committee has also recognized the need to develop follow-up strategies for determining the relevance of in vitro test results to human health, and moving genetic toxicology testing from the sole purpose of hazard identification toward a more quantitative risk assessment approach. In this context, a group of experts evaluated the potential utility of the emerging in vivo mutational assessment model commonly known as the Pig-a gene mutation assay to follow-up positive in vitro genetic toxicology findings and to generate robust dose-response data for quantitative assessment of the in vivo mutagenicity. The IVGT experts participating in this effort represented academia, industry, and government agencies from across the globe and addressed such issues as the optimal sample size and experimental design for generating robust dose-response data. This expert group concluded that the emerging Pig-a gene mutation assay holds great promise as an in vivo mutagenicity assay, either as a stand-alone study or integrated into repeat-dose toxicology studies, and therefore supports further validation of the model. PMID- 21976155 TI - The effect of betel nut chewing on contour and object masking. AB - The betel nut is a common stimulant in many Asian countries. We employed the masking task developed by Enns and Di Lollo (Trends in Cognitive Sciences, 4, 345 352, 1997) to investigate the effects of betel nuts on sensory and attentional processing. In the masking task, participants needed to identify a target that was masked by either a contour mask or an object mask. Sensory processing was assessed by examining target identification in the contour mask condition when the target was presented only centrally, whereas attentional processing was assessed by examining target identification in the object mask condition when the target was presented randomly in either a central or a parafoveal location. The results showed that chewing betel nut and chewing gum produced significant contour masking with a large effect size, similar to the pure control condition, in which participants chewed nothing, and the placebo control condition, in which what participants chewed was disguised. This suggests that neither betel nut nor gum affects sensory processing. Alternatively, betel nut chewing could produce a reduction in object masking for the habitual chewers and the nonchewers, suggesting an effect of betel nut on attentional processing. This concentrated attention was also observed in the placebo control condition; thus, it cannot be exclusively driven by the expectation effect. Also, chewing per se reduced the attentional distribution foveally. PMID- 21976153 TI - Regulatory gene network circuits underlying T cell development from multipotent progenitors. AB - Regulatory gene circuits enable stem and progenitor cells to detect and process developmental signals and make irreversible fate commitment decisions. To gain insight into the gene circuits underlying T cell fate decision making in progenitor cells, we generated an updated T-lymphocyte developmental gene regulatory network from genes and connections found in the literature. This reconstruction allowed us to identify candidate regulatory gene circuit elements underlying T cell fate decision making. Here, we examine the roles of these circuits in facilitating different aspects of the decision making process, and discuss experiments to further probe their structure and function. PMID- 21976157 TI - Surgical decompression of a caudal vertebral disc extrusion by dorsal laminectomy. AB - A 3.5-year-old female spayed Beagle cross was presented to our emergency and referral facility for the complaint of acute onset paralysis of the tail. A full physical and neurological examination was performed which confirmed the absence of motor function in the tail. Signs of superficial and deep pain sensation to the tail remained intact. Orthogonal view survey radiographs identified mineralization superimposed over the intervertebral foramen of the first and second caudal vertebrae. A dorsal laminectomy was performed for surgical decompression of the caudal nerve roots. On the fourth postoperative day, the patient exhibited good motor function of the tail. Neurological improvement continued and 11 days postoperatively the patient demonstrated normal neurological function, free range-of-motion of the tail, and it did not exhibit any signs of pain. Follow-up examination was performed 76 days after surgery, at which time the patient exhibited normal neurological function and signs of a pain free range-of-motion on manipulation of its tail. PMID- 21976156 TI - Normal levels of peripheral CD19(+) CD5(+) CLL-like cells: toward a defined threshold for CLL follow-up -- a GEIL-GOELAMS study. AB - BACKGROUND: The development of flow cytometry as a useful tool for the detection of minimal residual disease (MRD) in chronic lymphocytic leukemia (CLL) is potentially hampered by the fact that a normal subset of B-cells with a similar immunophenotype is present in the peripheral blood. This subset of CLL-like cells is not well defined in terms of frequency. METHODS: Here, we performed a multicenter study with a panel of four-color antibody combinations possibly useful for the detection of MRD in CLL, to establish the levels of normal CLL like cells in 49 healthy controls. ROC curves established the upper level of such cells at 4 * 10(-4) . The two best combinations were further applied to 419 samples from 117 treated CLL patients. RESULTS: The combinations CD19/CD5/CD43/CD79b and CD19/CD5/CD81/CD22 appeared very robust and well correlated to enumerate normal CLL-like cells in a lysis no-wash approach. In follow-up samples from CLL patients, they disclosed only 9.8% of the samples within the normal range. In more than 90% of the cases, it was thus possible to report confidently on the absence or presence of MRD in these patients. CONCLUSIONS: This manuscript reports on the frequency of CD19(+) CD5(+) B-cells in normal peripheral blood and confirms the combinations recommended by the European research initiative on CLL as being performing to assess remaining CLL cells above a threshold of 4 * 10(-4) white blood cells. PMID- 21976158 TI - Laboratory contributions to public health. PMID- 21976159 TI - Public health then and now: celebrating 50 years of MMWR at CDC. Foreword. PMID- 21976160 TI - Public health then and now: celebrating 50 years of MMWR at CDC. Introduction. PMID- 21976161 TI - A history of MMWR. PMID- 21976162 TI - The cornerstone of public health practice: public health surveillance, 1961- 2011. PMID- 21976163 TI - Evolution of epidemic investigations and field epidemiology during the MMWR era at CDC--1961-2011. PMID- 21976164 TI - History of statistics in public health at CDC, 1960-2010: the rise of statistical evidence. PMID- 21976165 TI - Changing methods of NCHS surveys: 1960-2010 and beyond. PMID- 21976166 TI - Vaccine-preventable diseases, immunizations, and MMWR--1961-2011. PMID- 21976167 TI - Control of health-care-associated infections, 1961-2011. PMID- 21976168 TI - AIDS: the early years and CDC's response. PMID- 21976169 TI - Fifty years of progress in chronic disease epidemiology and control. PMID- 21976170 TI - Injury prevention, violence prevention, and trauma care: building the scientific base. PMID- 21976171 TI - Environmental health in MMWR--1961-2010. PMID- 21976172 TI - Occupational epidemiology and the National Institute for Occupational Safety and Health. PMID- 21976173 TI - Trends in global health and CDC's international role, 1961-2011. PMID- 21976174 TI - Advice to a modern-day Rip Van Winkle: changes in state and local public health practice during the MMWR era at CDC. PMID- 21976175 TI - Rearrangements of a [36]octaphyrin triggered by nickel(II) metalation: metamorphosis to a directly meso-beta-linked diporphyrin. PMID- 21976176 TI - Analgesic effect of bilateral ultrasound-guided pudendal nerve blocks in management of interstitial cystitis. PMID- 21976177 TI - [Most desirable is to take care of oneself as long as possible. Transitions into old age with respect to habitation]. AB - In the past, retiring from work life was considered the central threshold for the transition into the life phase of old age. In the meantime, however, the de standardization of the life course calls for a redefinition of this transition: it has to be assumed that the exit from work life cannot be considered the only indicator for the transition into old age anymore. The results presented here address transitions into old age with respect to habitation. Adopting a qualitative empirical approach, older peoples' attitudes towards housing arrangements in late adulthood and at the end of life were surveyed and analyzed. The article focuses on the interviewees' descriptions regarding their anticipated and preferred housing scenarios which then serve as a basis for the reconstruction of concepts of transition into old age with respect to habitation. PMID- 21976178 TI - [Patients unable to give consent and without a power of attorney or legal guardian in the geriatric department]. AB - BACKGROUND: The importance of powers of attorney and legal guardians for patients in hospitals who are unable to make decisions for themselves is growing. Without an authorized person in these cases, treatment and discharge are more difficult. The goal of this study was to describe the problem from the point of view of an acute geriatric department and discuss the problems with respect to duration and expense of hospitalization. In addition, an attempt was undertaken to improve cooperation with the legal authorities in order to reduce the time required to process the request for the appointment of a legal guardian. MATERIALS AND METHOD: A total of 24 consecutive patients appointed a legal guardian during their hospitalization were compared with 25 patients after the intervention. RESULTS: Of all patients treated in 2008, 2.1% needed an application for an appointed legal guardian (4.6% in 2009). These patients were more seriously ill and treated longer in the hospital compared to all patients. The intervention reduced the length of stay on average by 2.8 days. Independent risk factors for longer treatment were more seriously ill patients and later submission of the application after admittance to the hospital. For patients above the maximum length of stay, the move to a nursing home and the need of a professional legal guardian prolonged significantly the hospital treatment compared to those below the maximum length of stay. CONCLUSION: The data demonstrate that the German DRG system does not sufficiently consider the difficult management caused by patients without the ability to give consent to treatment and without a valid power of attorney. The time required until a professional legal guardian is appointed is too long for patients in a hospital. The necessity of a power of attorney has to be promoted more intensely to the public. Currently, the only two ways to minimize the problem is to identify the patients without, but needing a power of attorney as quickly as possible and to remain in close contact with the legal authorities. PMID- 21976179 TI - Superior and inferior gluteal artery perforator flaps in reconstruction of gluteal and perianal/perineal hidradenitis suppurativa lesions. AB - BACKGROUND: Hidradenitis suppurativa is a debilitating disease with a tendency to form abscesses, sinus tracts, and scar formation. In this report, our experience with reconstruction of hidradenitis lesions of the gluteal and perianal/perineal area using superior and inferior gluteal artery perforator flaps (SGAP and IGAP) are discussed. PATIENTS: A prospective study was conducted in collaboration with the general surgery department for patients with gluteal and perianal/perineal hidradenitis suppurativa between December 2005 and May 2010. Data of each patient included age, sex, disease localization, duration of symptoms, comorbidities, size of defect after excision, perforator flap chosen, complications, and postoperative follow-up. RESULTS: Eleven SGAP and six IGAP flaps were used in 12 patients with gluteal and perianal/perineal involvement. There was one flap necrosis for whom delayed skin grafting was performed. The mean follow-up period was 20 months without recurrences. CONCLUSION: Patients with gluteal and perineal/perianal hidradenitis suppurativa are usually neglected by surgeons because of lack of collaboration of general and plastic surgery departments. Most surgical treatment options described in the literature such as secondary healing after excision and skin grafting prevent patients from returning to daily life early, and cause additional morbidities. Fasciocutaneous flaps other than perforator flaps may be limited by design such that both gluteal regions may have to be used for reconstruction of large defects. SGAP and IGAP flaps have long pedicles with a wide arc of rotation. Large defects can be reconstructed with single propeller flap designs, enabling preservation of the rest of the perforators of the gluteal region. PMID- 21976180 TI - Nerve growth factor combined with an epineural conduit for bridging a short nerve gap (10 mm). A study in rabbits. AB - The purpose of this study was to evaluate the effect of direct administration of nerve growth factor (NGF) into an epineural conduit across a short nerve gap (10 mm) in a rabbit sciatic nerve model. The animals were divided into two groups. In group 1, n = 6, a 10-mm defect was created in the sciatic nerve and bridged with an epineural flap. A dose of 1 MUg of NGF was locally administered daily for the first 21 days. NGF administration was made inside the epineural flap using a silicone reservoir connected to a silicone tube. In group 2, n = 6, the 10-mm defect was bridged with a nerve graft. This group did not receive any further treatment. At 13 weeks, all animals, before euthanasia, underwent electromyography (EMG) studies and then specimen sent for histology morphometric analysis. NGF administration ensured a significantly increased average number of myelinated axons per MUm(2) (P = 0.028) and promoted fiber maturation (P = 0.031) and better EMG results (P = 0.046 for latency P = 0.048 for amplitude), compared with the control group. Although nerve grafts remain the gold standard for peripheral nerve repair, NGF-treated epineural conduits represent a good alternative, particularly when an unfavorable environment for nerve grafts is present. PMID- 21976181 TI - A free composite de-epithelialized anterolateral thigh and the vastus lateralis muscle flap for the reconstruction of a large defect of the anterior skull base: a case report. AB - Reconstruction of the anterior skull base is one of the greatest challenges for reconstructive surgeons. Sometimes, the defect is so large that a local flap is insufficient for the reconstruction. In this report, we present a case of malignant meningioma of the anterior skull base. The tumor was treated by surgical excision resulting in a large defect from the anterior skull base to the nasal cavity. The entire defect was within the cranial vault. The reconstruction was achieved using a free composite de-epithelialized anterolateral thigh and the vastus lateralis muscle flap. Postoperative monitoring included hand Doppler and daily endoscopic inspection. This patient was satisfied with the cosmetic result. After 10 months, magnetic resonance imaging (MRI), performed to assess the flap, demonstrated that the volume of the de-epithelialized skin paddle of the anterolateral thigh flap had not changed, and that there was no tissue atrophy between the patient's eyes that could have resulted in deformity. PMID- 21976182 TI - Intraoperative color Doppler sonography in the elevation of anterolateral thigh flap. PMID- 21976183 TI - Intestinal transplantation using cuff-glue sutureless technique for microanastomosis in rats. PMID- 21976184 TI - Novel microsurgical precision grip and spring-handled instrument with a variable stabilizer. PMID- 21976185 TI - Delivery of helium-oxygen mixture during spontaneous breathing: evaluation of three high-concentration face masks. AB - PURPOSE: To evaluate the efficacy of delivering a mixture of helium and oxygen gas (He-O2) in spontaneous ventilation. Three high oxygen flow reservoir masks were tested: the Heliox21, specifically designed for helium; the Hi-Ox80 mask, with an inspiratory and an expiratory valve; and a standard high-concentration face mask. METHODS: This prospective randomized crossover study was performed in six healthy volunteers in a laboratory setting. Volunteers breathed a mixture of 78% He/22% O2 through each of the masks under two different breathing conditions (rest and hyperventilation: minute ventilation of 14.9 +/- 6.1 and 26.7 +/- 8.7 L min(-1), respectively) and four different He-O2 flow rates (7, 10, 12, and 15 L min(-1)). RESULTS: A nasopharyngeal catheter was used to estimate He pharyngeal concentration (Fp [He]) in the airways in order to determine the percentage of contamination with room air (% air cont) at end-expiration. Under all testing conditions, the Hi-Ox80 mask presented a significantly lower % air cont. During resting breathing pattern, a Fp [He] higher than 50% was achieved in 54% of the tests performed with the Hi-Ox80 mask compared to 29% for the Heliox21 mask and only 17% for the standard mask. At hyperventilation, a Fp [He] higher than 50% was achieved in 17% of the tests performed with the Hi-Ox mask compared to 4% for the other two masks. CONCLUSION: He-O2 administration via the usual high concentration reservoir masks results in significant dilution by room air. The Hi Ox80 mask minimized room air contamination and much more frequently achieved a pharyngeal He concentration higher than 50%. PMID- 21976186 TI - A metabolomic approach for diagnosis of experimental sepsis. AB - BACKGROUND: The search for reliable diagnostic biomarkers of sepsis remains necessary. Assessment of global metabolic profiling using quantitative nuclear magnetic resonance (NMR)-based metabolomics offers an attractive modern methodology for fast and comprehensive determination of multiple circulating metabolites and for defining the metabolic phenotype of sepsis. OBJECTIVE: To develop a novel NMR-based metabolomic approach for diagnostic evaluation of sepsis. METHODS: Male Sprague-Dawley rats (weight 325-375 g) underwent cecal ligation and puncture (n = 14, septic group) or sham procedure (n = 14, control group) and 24 h later were euthanized. Lung tissue, bronchoalveolar lavage (BAL) fluid, and serum samples were obtained for (1)H NMR and high-resolution magic angle spinning analysis. Unsupervised principal components analysis was performed on the processed spectra, and a predictive model for diagnosis of sepsis was constructed using partial least-squares discriminant analysis. RESULTS: NMR-based metabolic profiling discriminated characteristics between control and septic rats. Characteristic metabolites changed markedly in septic rats as compared with control rats: alanine, creatine, phosphoethanolamine, and myoinositol concentrations increased in lung tissue; creatine increased and myoinositol decreased in BAL fluid; and alanine, creatine, phosphoethanolamine, and acetoacetate increased whereas formate decreased in serum. A predictive model for diagnosis of sepsis using these metabolites classified cases with sensitivity and specificity of 100%. CONCLUSIONS: NMR metabolomic analysis is a potentially useful technique for diagnosis of sepsis. The concentrations of metabolites involved in energy metabolism and in the inflammatory response change in this model of sepsis. PMID- 21976187 TI - Tidal volume delivery during surfactant administration in the delivery room. AB - PURPOSE: Reduced mortality for infants born at less than 30 weeks' gestation after prophylactic surfactant administration has led many to advocate routine intubation and administration of surfactant in all infants at risk of respiratory distress syndrome. However, surfactant administration is associated with adverse events including bradycardia, changes in cerebral blood flow and endotracheal tube obstruction. The aim of this study was to analyse respiratory function immediately before and after surfactant administration in the delivery room. METHODS: We reviewed video recordings of the initial resuscitation in the delivery room of infants born at less than 32 weeks' gestation between February 2007 and March 2010. Positive pressure ventilation was delivered with either a Neopuff T-piece or self-inflating bag. Respiratory parameters were recorded with a respiratory function monitor (RFM). Each RFM recording was analysed for 30 s before and 2 min after surfactant administration. RESULTS: Of 230 infants recorded during the study period 16 infants received surfactant in the delivery room. Their mean (standard deviation, SD) gestation and birth weight were 25 (1) weeks and 757 (249) g, respectively. Complete airway obstruction was seen in 4/16 (25%) infants. The median (interquartile range, IQR) duration of this obstruction was 16 (8-27) s. The median (IQR) expired tidal volume before surfactant delivery was 8.0 (5.2-11.2) mL/kg compared to 4.6 (4.1-7.3) mL/kg (p = 0.03) after surfactant administration. CONCLUSION: Substantial tidal volume changes occur before, during and after surfactant administration in the delivery room. Complete airway obstruction is common. Monitoring respiratory function during this procedure may help to assess the delivered tidal volume and airway pressures after surfactant treatment. PMID- 21976189 TI - Is accuracy of weight perception associated with health risk behaviors in a diverse sample of obese adolescents? AB - Current evidence is equivocal as to whether adolescent's perception of weight status is linked to both healthy and risky behaviors. This study examined the association between accurate and inaccurate perception of weight and self reported health and risk behaviors among a diverse sample of obese, urban adolescents. Data were analyzed from 1,180 participants in the 2009 Philadelphia Youth Risk Behavior Survey. Health behaviors of obese students self-identifying as very or slightly overweight were compared to obese students who underestimated their weight status. Accurate self-identifiers of weight status were significantly more likely to report trying to lose weight, bullying victimization, and suicide attempts as compared to obese students underestimating their weight status. Findings suggest that it is important for school nurses to understand that perceived weight status confers distinct risk profiles and differing needs for health-related services related to the physical, mental, and social health of adolescents. PMID- 21976188 TI - New insights into weaning from mechanical ventilation: left ventricular diastolic dysfunction is a key player. AB - PURPOSE: To investigate the diagnostic performance of Doppler echocardiography (DE) in predicting the outcome of weaning from mechanical ventilation in patients without overt cardiac disease. METHODS: Fifty critical care noncardiac patients who fulfilled predetermined criteria for weaning underwent DE before and at the end of spontaneous breathing trial (pre-SBT/end-SBT, respectively). "Conventional" mitral inflow analysis and "advanced" DE parameters [tissue Doppler imaging (TDI)-derived mitral/tricuspid annular velocities and color M mode Doppler velocity of propagation (V p)] were used to assess left ventricular (LV) diastolic function/filling pressures. Weaning was considered successful if patients had been extubated after successful SBT and sustained spontaneous breathing for more than 48 h. RESULTS: Twenty-eight patients (56%) failed weaning: 23 patients failed SBT and 5 required reintubation within 48 h. Weaning failure was associated with the degree of LV diastolic dysfunction at pre-SBT (P = 0.01). Patients who failed weaning presented evidence of increased LV filling pressures at pre-SBT, by demonstrating increased E/E m and E/V p ratios compared with patients with successful outcome (P <= 0.004); pre-SBT values of lateral E/E m greater than 7.8 and E/V p greater than 1.51 predicted weaning failure with an area under the curve, sensitivity (%), and specificity (%) of 0.86, 79, and 100, and 0.74, 75, and 73, respectively. Lateral E/E m was the only factor independently associated with weaning failure before SBT; OR (95% CI) 5.62 (1.17 26.96), P = 0.03. CONCLUSIONS: Our findings suggest that LV diastolic dysfunction is significantly associated with weaning outcome in critically ill patients with preserved LV systolic function. An E/E m ratio greater than 7.8 may identify patients at high risk of weaning failure. PMID- 21976190 TI - Efficacy of alcohol-based hand sanitizer on hands soiled with dirt and cooking oil. AB - Handwashing education and promotion are well established as effective strategies to reduce diarrhea and respiratory illness in countries around the world. However, access to reliable water supplies has been identified as an important barrier to regular handwashing in low-income countries. Alcohol-based hand sanitizer (ABHS) is an effective hand hygiene method that does not require water, but its use is not currently recommended when hands are visibly soiled. This study evaluated the efficacy of ABHS on volunteers' hands artificially contaminated with Escherichia coli in the presence of dirt (soil from Tanzania) and cooking oil. ABHS reduced levels of E. coli by a mean of 2.33 log colony forming units (CFU) per clean hand, 2.32 log CFU per dirt-covered hand, and 2.13 log CFU per oil-coated hand. No significant difference in efficacy was detected between hands that were clean versus dirty or oily. ABHS may be an appropriate hand hygiene method for hands that are moderately soiled, and an attractive option for field settings in which access to water and soap is limited. PMID- 21976191 TI - Surveillance of influenza A and the pandemic influenza A (H1N1) 2009 in sewage and surface water in the Netherlands. AB - The role of the water cycle in spreading human pathogenic influenza viruses is poorly studied and is not considered to be significant. However, gastrointestinal symptoms developed in a large proportion of influenza A (H1N1) 2009 virus infected people during the pandemic in 2009 and fecal shedding was reported. This fecal route could potentially play a role in the entry of human pathogenic influenza viruses in to the water cycle. Monitoring of influenza viruses in sewage and surface water during the pandemic in 2009 showed that influenza A viruses were detected in sewage and surface water. However, the pandemic influenza A (H1N1) 2009 virus was not detected. These findings imply that the water cycle did not play a relevant role in spreading the pandemic influenza virus during the epidemic in the Netherlands in 2009. Analyses of deliberately contaminated water samples confirmed the ability of quantitative RT-PCR to detect influenza viruses in sewage samples whereas the analysis of large volumes of surface water was strongly hampered by the presence of PCR-inhibiting substances. PMID- 21976193 TI - Recovery of Salmonella from biofilms in a headwater spring ecosystem. AB - Salmonellae are pathogenic bacteria often detected in waters impacted by human or animal wastes. In order to assess the fate of salmonellae in supposedly pristine environments, water and natural biofilm samples along with snails (Tarebia granifera) and crayfish (Procambarus clarkia) were collected before and up to 7 days following four precipitation events from sites within the headwater springs of Spring Lake, San Marcos, TX. The samples were analyzed for the presence of salmonellae by polymerase chain reaction (PCR) after semi-selective enrichment. Salmonellae were detected in one water sample directly after precipitation only, while detection in ten biofilm and two crayfish samples was not related to precipitation. Salmonellae were not detected in snails. Characterization of isolates by rep-PCR revealed shared profiles in water and biofilm samples, biofilm and crayfish samples, and biofilm samples collected 23 days apart. These results suggest that salmonellae are infrequently washed into this aquatic ecosystem during precipitation runoff and can potentially take up residency in biofilms which can help facilitate subsequent long-term persistence and eventual transfer through the food chain. PMID- 21976192 TI - Daily measures of microbes and human health at a non-point source marine beach. AB - Studies evaluating the relationship between microbes and human health at non point source beaches are necessary for establishing criteria which would protect public health while minimizing economic burdens. The objective of this study was to evaluate water quality and daily cumulative health effects (gastrointestinal, skin, and respiratory illnesses) for bathers at a non-point source subtropical marine recreational beach in order to better understand the inter-relationships between these factors and hence improve monitoring and pollution prevention techniques. Daily composite samples were collected, during the Oceans and Human Health Beach Exposure Assessment and Characterization Health Epidemiologic Study conducted in Miami (Florida, USA) at a non-point source beach, and analyzed for several pathogens, microbial source tracking markers, indicator microbes, and environmental parameters. Analysis demonstrated that rainfall and tide were more influential, when compared to other environmental factors and source tracking markers, in determining the presence of both indicator microbes and pathogens. Antecedent rainfall and F+ coliphage detection in water should be further assessed to confirm their possible association with skin and gastrointestinal (GI) illness outcomes, respectively. The results of this research illustrate the potential complexity of beach systems characterized by non-point sources, and how more novel and comprehensive approaches are needed to assess beach water quality for the purpose of protecting bather health. PMID- 21976194 TI - Combining modeling and monitoring to study fecal contamination in a small rural catchment. AB - The present study sought to identify Escherichia coli sources in a small catchment and to use the agro-hydrological model soil and water assessment tool (SWAT) to estimate their impact on river water quality. The innovative aspects of this research are to assess the hourly variations of fecal contamination and to take these variations into account in the model to provide a better evaluation of river quality. Thus, water samples were taken weekly at the river outlet (n = 4) and 24-h monitoring sessions were performed during low and high-flow periods (n = 74). E. coli variations were found to be primarily linked to rainfall and not to resuspension mechanisms. Subdaily fluctuations and deviations were +/-0.33 log(10) cfu/100 mL and +/-0.70 log(10) cfu/100 mL for dry (<3 mm/day) and wet (>3 mm/day) weather, respectively. After river flow calibration, all known pollution sources (septic systems, manure spreading, farm discharges) were introduced into SWAT. The model reproduced the fecal contamination in the river and the use of subdaily deviations allowed us to evaluate the simulation quality and compare grab samplings with simulated daily E. coli concentration, thus confirming that the performance of the model is better when additional information on hourly concentration variations is used. PMID- 21976195 TI - Long-term study of migration of volatile organic compounds from cross-linked polyethylene (PEX) pipes and effects on drinking water quality. AB - The objectives of this study were to investigate migration of volatile organic compounds (VOCs) from cross-linked polyethylene (PEX) pipes used for drinking water produced by different production methods, and to evaluate their potential risk for human health and/or influence on aesthetic drinking water quality. The migration tests were carried out in accordance with EN-1420-1, and VOCs were analysed by gas chromatography-mass spectrometry. The levels of VOC migrating from new PEX pipes were generally low, and decreasing with time of pipe use. No association was found between production method of PEX pipes and concentration of migration products. 2,4-di-tert-butyl phenol and methyl tert-butyl ether (MTBE) were two of the major individual components detected. In three new PEX pipes, MTBE was detected in concentrations above the recommended US EPA taste and odour value for drinking water, but decreased below this value after 5 months in service. However, the threshold odour number (TON) values for two pipes were similar to new pipes even after 1 year in use. For seven chemicals for which conclusions on potential health risk could be drawn, this was considered of no or very low concern. However, odour from some of these pipes could negatively affect drinking water for up to 1 year. PMID- 21976196 TI - Does calcium in drinking water modify the association between nitrate in drinking water and risk of death from colon cancer? AB - The objective of this study was to explore whether calcium (Ca) levels in drinking water modified the effects of nitrate on colon cancer risk. A matched case-control study was used to investigate the relationship between the risk of death from colon cancer and exposure to nitrate in drinking water in Taiwan. All colon cancer deaths of Taiwan residents from 2003 through 2007 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth and year of death. Information on the levels of nitrate nitrogen (NO(3)-N) and Ca in drinking water have been collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cases and controls was assumed to be the source of the subject's NO(3)-N and Ca exposure via drinking water. We observed evidence of an interaction between drinking water NO(3)-N and Ca intake via drinking water. This is the first study to report effect modification by Ca intake from drinking water on the association between NO(3)-N exposure and risk of colon cancer mortality. PMID- 21976197 TI - Effects of tap water processing on the concentration of disinfection by-products. AB - AIM: This study examined the effects on disinfection by-product (DBP) concentrations of common household methods for processing drinking water. METHODS: We investigated the effects of refrigerator storage, jug filtering, boiling in an electric kettle, and supply from an instant boiling water unit, with or without filtering, on four species of trihalomethanes (THMs) and nine species of haloacetic acids (HAAs) in water ready for consumption in Sydney, Australia. Water samples were processed in such a way as to simulate real life conditions for drinking filtered water or hot water drinks prepared from tap water drawn from public water supply systems. RESULTS: There was a large reduction in total THMs in kettle-boiled water, instant boiled water, jug filtered water and instant boiled-filtered water (reductions of 85.8, 93.5, 92.6 and 87.8% of their concentration in tap water respectively). Refrigerator storage did not appear to have a consequential effect on THMs or HAAs. Jug-filtering and instant boiling and filtering resulted in large decreases (77-94%) in all species of HAAs in tap water. CONCLUSION: This study suggests that different methods of processing tap water can change DBP concentration to an extent that would have a meaningful impact on exposure assessment in epidemiological studies. PMID- 21976198 TI - Occurrence of water-borne enteric viruses in two settlements based in Eastern Chad: analysis of hepatitis E virus, hepatitis A virus and human adenovirus in water sources. AB - Hepatitis E virus (HEV) is a common cause of water-borne acute hepatitis in areas with poor sanitation. In 2004 an outbreak of HEV infection affected around 2,000 people in Eastern Chad (Dar Sila). This paper describes the decrease in the incidence of acute jaundice syndrome (AJS) from 2004 until 2009 when a mean incidence of 0.48 cases/1,000 people/year was recorded in the region. Outbreaks of AJS were identified in some of the camps in 2007 and 2008. Moreover, water samples from drinking water sources were screened for human adenoviruses considered as viral indicators and for hepatitis A virus and HEV. Screening of faecal samples from donkeys for HEV gave negative results. Some of the samples were also analysed for faecal coliforms showing values before disinfection treatment between 3 and >50 colony forming units per 100 mL. All water samples tested were negative for HEV and HAV; however, the presence of low levels of human adenoviruses in 4 out of 16 samples analysed indicates possible human faecal contamination of groundwater. Consequently, breakdowns in the treatment of drinking water and/or increased excretion of hepatitis viruses, which could be related to the arrival of a new population, could spread future outbreaks through drinking water. PMID- 21976199 TI - Quality assessment of roof-harvested rainwater in the West Bank, Palestinian Authority. AB - Rain harvesting is becoming more common in the Palestinian Territories as a result of drinking water scarcity. Although it might pose serious human health risk, this water is being consumed without treatment in many areas of the West Bank. The present study evaluates the physicochemical and microbial quality of harvested rainwater that is used as potable water in the West Bank. Samples from roof-harvested rainwater storage tanks (n = 42) were collected in summer (SS) 2006/winter (WS) 2007. Physicochemical parameters measured were: temperature, pH, electrical conductivity, salinity, total dissolved solids, turbidity, nitrate, copper and lead. With few exceptions, all these parameters were within WHO guideline values. All samples (100%) were found to contain coliforms and to be heavily contaminated with heterotrophic bacteria. About 67% of all samples were contaminated with fecal coliforms. Specific PCR technique confirmed the presence of five pathogenic microorganisms that can be ordered according to their prevalence as: Citrobacter (83%) > Acinetobacter (78%) > Aeromonas (52%) > Pseudomonas and Campylobacter (7%). Prevalence of microorganisms in SS was higher than in WS. Although the physicochemical quality of most harvested rainwater samples was in accordance with WHO guidelines for drinking water, stored rainwater was significantly contaminated with bacteria resulting in significant human health risk from infectious diseases. PMID- 21976200 TI - Electrochemical inactivation kinetics of boron-doped diamond electrode on waterborne pathogens. AB - A boron-doped diamond (BDD) electrode was constructed as a water disinfector for the inactivation of water borne pathogens. The bactericidal effect of the disinfector was evaluated on artificially contaminated waters containing, respectively, Escherichia coli, Pseudomonas aeruginosa and Legionella pneumophila at high density. By treating the bacterial suspensions with 4 V of constant voltage between the BDD and the counter-electrode for 50 min, the population of E. coli and P. aeruginosa decreased from (10E + 7-8 colony-forming unit mL(-1)) to below the detection limits of the colony-formation method. Meanwhile, L. pneumophila were reduced to virtually zero when analyzed by fluorescence-based staining. The influences of production parameters (voltage, NaCl concentration and flow rate) on the disinfection kinetics of the BDD disinfector were examined with respect to operational conditions. Voltage was the most significant factor for adjusting the extent of electrolysis, followed by NaCl concentration and flow rate, to influence the disinfection efficiency. The disinfection of natural river water samples containing numerous microbes was performed for a practicability investigation of the BDD electrode. Approximately 99.99% bactericidal efficiency was confirmed by viability detection for E. coli and common germs in treated water. The results showed that the BDD electrode is a promising tool for various wastewater disinfections to combat waterborne diseases. PMID- 21976201 TI - Occurrence of norovirus and other enteric viruses in untreated groundwaters of Korea. AB - A total of 39 water samples from 23 different groundwater wells in Korea were collected and analyzed in order to monitor the occurrence of norovirus (NoV) and other indicator microbes as the first part of a national survey of groundwater. More than 500 L of untreated groundwater were filtered through 1MDS filters. Following elution and concentration by organic flocculation, PCR and sequence analysis were employed to detect and identify NoV, enterovirus, rotavirus, hepatitis A virus and adenovirus (Adv). Somatic and F-specific phages, heterotrophic bacteria, total coliforms and Escherichia coli were also analyzed to infer possible fecal contamination. NoVs were detected in 18% of the 39 samples. Five out of seven NoV-positive samples (71%) were identified as GI while the other two (29%) were GII. Enteroviruses and Advs were detected in two and three samples, respectively. Rotavirus and hepatitis A virus were not detected. Total coliforms, E. coli and coliphages were detected in 49, 15 and 13% of the samples, respectively, but did not appear to be suitable indicators of enteric virus contamination in groundwater. These results suggest that additional treatment may be needed for a significant number of groundwaters prior to use as drinking water. PMID- 21976202 TI - Beach communications: a need for evaluation of current approaches. AB - AIMS: Programs to notify the public about water quality at beaches are developed at the state and local levels. We sought to characterize the messages and message delivery options in use, and information about the effectiveness of these beach notification programs. METHODS: A telephone survey of 37 US state, tribal and territorial and 18 county, city or local beach programs was conducted to characterize current public notification practices and any evaluations of those practices. RESULTS: Beach notification practices vary substantially at the state and local levels. Color-coded signs or flags are commonly used, but not universally, and the color schemes and their meanings vary. New communication approaches utilizing text messaging and the internet are in use or under development for local use. Few communication methods had undergone systematic evaluations of their content, delivery methods or effectiveness in promoting behavior change. CONCLUSION: The prevention of waterborne illness requires communications that effectively promote the avoidance of swimming when water quality is impaired. Current communication practices are variable and generally have not undergone formal evaluations for their effectiveness. It is not known whether or how they impact health risk. PMID- 21976203 TI - Outbreak of acute gastroenteritis due to a washwater-contaminated water supply, Switzerland, 2008. AB - An operating error in a sewage treatment plant led to severe drinking water contamination in a well-defined district of a suburban municipality of Zurich, Switzerland. Despite the alert issued to the local population on the same day advising people not to consume the contaminated water, cases of acute gastroenteric diseases were subsequently observed. Considerable faecal contamination was detected the day after the incident in water samples taken up to 500 m from the sewage plant. In a retrospective epidemiological study involving 240 persons living in the affected area, 126 cases of acute gastrointestinal illness were documented. The epidemic curve revealed a peak incidence two days after the event. Stool samples from 11 of 20 patients were positive for noroviruses or Campylobacter jejuni. Although these microorganisms were not detected in the contaminated water, the subsequently conducted case control study among the surveyed population showed that consumption of contaminated drinking water was associated with gastrointestinal illness (odds ratio 29.1; 95% confidence interval: 9.8-86.4; p = 0.001). The study also revealed the very probable time period of infection. We present the dimension and chronology of this outbreak and discuss the reasons for its localised and temporary spread. PMID- 21976204 TI - Microbiologic effectiveness of boiling and safe water storage in South Sulawesi, Indonesia. AB - In Indonesia, where diarrhea remains a major cause of mortality among children <5 years, the government promotes boiling of drinking water. We assessed the impact of boiling on water quality in South Sulawesi. We surveyed randomly selected households with at least one child <5 years old in two rural districts and tested source and stored water samples for Escherichia coli contamination. Among 242 households, 96% of source and 51% of stored water samples yielded E. coli. Unboiled water samples, obtained from 15% of households, were more likely to yield E. coli than boiled samples [prevalence ratios (PR) = 2.0, 95% confidence interval (CI) 1.7-2.5]. Water stored in wide-mouthed (PR = 1.4, 95% CI = 1.1-1.8) or uncovered (PR = 1.8, 95% CI = 1.3-2.4) containers, or observed to be touched by the respondent's hands (PR = 1.6, 95% CI = 1.3-2.1) was more likely to yield E. coli. A multivariable model showed that households that did not boil water were more likely to have contaminated stored water than households that did boil water (PR = 1.9, 95% CI = 1.5-2.3). Although this study demonstrated the effectiveness of boiling in reducing contamination, overall impact on water quality was suboptimal. Future studies are needed to identify factors behind the success of boiling water in Indonesia to inform efforts to scale up other effective water treatment practices. PMID- 21976205 TI - Application of an optimized system for the well-defined exposure of human lung cells to trichloramine and indoor pool air. AB - In this study an in vitro exposure test to investigate toxicological effects of the volatile disinfection by-product trichloramine and of real indoor pool air was established. For this purpose a set-up to generate a well-defined, clean gas stream of trichloramine was combined with biotests. Human alveolar epithelial lung cells of the cell line A-549 were exposed in a CULTEX((r)) device with trichloramine concentrations between 0.1 and 40 mg/m(3) for 1 h. As toxicological endpoints the cell viability and the inflammatory response by the cytokines IL-6 and IL-8 were investigated. A decreasing cell viability could be observed with increasing trichloramine concentration. An increase of IL-8 release could be determined at trichloramine concentrations higher than 10 mg/m(3) and an increase of IL-6 release at concentrations of 20 mg/m(3). Investigations of indoor swimming pool air showed similar inflammatory effects to the lung cells although the air concentrations of trichloramine of 0.17 and 0.19 mg/m(3) were much lower compared with the laboratory experiments with trichloramine as the only contaminant. Therefore it is assumed that a mixture of trichloramine and other disinfection by-products in the air of indoor pool settings contribute to that effect. PMID- 21976206 TI - Effect of storage of shelled Moringa oleifera seeds from reaping time on turbidity removal. AB - Moringa oleifera is an indigenous plant to Malaysia whose seeds are used for water purification. Many studies on Moringa oleifera have shown that it is highly effective as a natural coagulant for turbidity removal. In this study, two different methods for extraction of Moringa's active ingredient were investigated. Results of sodium chloride (NaCl) and distilled water extraction of Moringa oleifera seeds showed that salt solution extraction was more efficient than distilled water in extracting Moringa's active coagulant ingredient. The optimum dosage of shelled Moringa oleifera seeds extracted by the NaCl solution was comparable with that of the conventional chemical coagulant alum. Moreover, the turbidity removal efficiency was investigated for shelled Moringa oleifera seeds before drying in the oven under different storage conditions (i.e. open and closed containers at room temperature, 27 degrees C) and durations (fresh, and storage for 2, 4, 6 and 8 weeks from the time the seeds were picked from the trees). Our results indicate that there are no significant differences in coagulation efficiencies and, accordingly, turbidity removals between the examined storage conditions and periods. PMID- 21976207 TI - Genotyping of Acanthamoeba isolated from water in recreational areas of Tehran, Iran. AB - A comprehensive survey assessing the presence of Acanthamoeba was conducted on 50 samples from water sources in parks and public squares from 22 municipal districts of Tehran, Iran. The prevalence and genotypes of Acanthamoeba were determined by PCR and the PCR fragments of ribosomal RNA genes sequenced. Sixteen (32%) samples were positive for Acanthamoeba spp. Sequence analysis revealed that the positive isolates belonged to the T4 and T5 genotypes. Fourteen isolates (87.5%) were T4, and two (12.5%) were T5. Acanthamoeba may be a problematic organism for contact lens wearers and for immunocompromised individuals. In Iran, Acanthamoeba keratitis has increased in recent years, mainly due to poor hygiene in contact lens wearers. A thorough survey for the prevalence of this amoeba could have a significant role in prevention of disease. This is the first report of the T5 genotype from water in recreational areas of Tehran. PMID- 21976208 TI - Assessing the potential risks of burial practices on groundwater quality in rural north-central Nigeria. AB - Several cultures of north-central Nigeria do not use community cemeteries. Instead, human remains are buried in and around family compounds, often in shallow and sometimes unmarked graves. At several locations, graves and drinking water wells end up too close to be presumed environmentally safe. This paper reports findings of a pilot study that explored the potential for groundwater contamination from gravesites in some rural settlements of north-central Nigeria. Preliminary results suggest that the long-standing burial practices among some cultures of rural north-central Nigeria may potentially compromise groundwater quality, which is, by far, their most important source of drinking water. PMID- 21976209 TI - How dual bridging atoms tune structural and optoelectronic properties of ladder type heterotetracenes?--a theoretical study. AB - Ladder-type heterotetracenes possessing fully ring-fused structures are a promising class of optoelectronic materials in terms of the lack of any conformational disorder, intense emission and high carrier mobility. To uncover how dual bridging atoms tune their structural and optoelectronic properties, the heterotetracenes were systematically investigated by theoretical calculations from several aspects, such as (i) the geometrical structures of ground and excited states; (ii) the highest occupied molecular orbitals (HOMO), the lowest unoccupied molecular orbitals (LUMO); (iii) ionization potentials (IP), electron affinities (EA), hole extraction potentials (HEP), electron extraction potentials (EEP), internal reorganization energies (lambda(int)) and transfer integrals (V); (iv) the absorption and emission spectra in vacuum and the dichloromethane (CH(2)Cl(2)) solvent, band gaps (E(g)), excitation energies at the lowest singlet (E(S1)) or triplet (E(T1)) states as well as radiative lifetimes (tau). The theoretical investigations may be useful for finding new leading materials and are likely to provide important information for improving their photoelectric performance. PMID- 21976210 TI - A study on the attitudes and behavioural influence of construction waste management in occupied Palestinian territory. AB - As a step towards comprehending what drives the management of construction waste in the occupied Palestinian territory, this paper quantifies construction waste generation and examines how the local contractors' waste management attitudes and behaviour are influenced. Collection of data was based on a survey, carried out in the southern part of the West Bank between April and May 2010. The survey targeted contractors who specialized in the construction of buildings. A logistic regression model was used to investigate the relationship between various attributes and the attitudes and behaviour that the local contractors demonstrate towards waste management. The results showed that during the construction of buildings, 17 to 81 kg of construction waste are generated per square metre of building floor. Although the area of a building is the key factor determining 74.8% of the variation of construction waste generation, the employment of labour intensive techniques in the study area means that human factors such as the contractor's attitude and behaviour towards waste management, exert a key influence on waste generation. Attitudes towards the 3Rs of waste minimization and behaviour towards waste disposal are generally positive with smaller contractors exhibiting more positive attitudes and more satisfactory behaviour towards waste management. Overall, while contractors' behaviour towards waste sorting and disposal tends to be more satisfactory among contractors who are more conscious about the potential environmental impacts of construction waste, it was generally observed that in the absence of a regulatory framework, the voluntary attitudes and behaviour among the local contractors are mostly driven by direct economic considerations. PMID- 21976211 TI - Exclusion of older immigrants from the former Soviet Union to Finland: the meaning of intergenerational relationships. AB - This article discusses factors that affect the exclusion of older immigrants in Finland. The meaning of intergenerational relationships to older immigrants in an everyday life context is versatile and comprises support, commitment and expectations between generations. The second and third generations are doing their best to cope with their own everyday life and integration process while being under the pressure to meet the varied expectations of the first generation. The topic is explored using qualitative data drawn from interviews with three generation families from the former Soviet Union. The study found that satisfying factors of everyday life, such as housing or activities offered by society and the possibility to live close to the children and grandchildren reflect the feeling of inclusion to the host society. Dissatisfying feelings such as hostile attitudes, deficient language acquisition and a longing for the former home country, people and places there, affect the feelings of social and emotional exclusion. The exclusion faced by older immigrants in the Finnish society seems to be more complicated and sensitive than is generally recognized; it is illustrated through the emotions of immigrant elders rather than through their active actions or participation. PMID- 21976212 TI - Attribution of human papillomavirus types to cervical intraepithelial neoplasia and invasive cancers in Southern China. AB - The attribution of individual human papillomavirus (HPV) types to cervical neoplasia, especially intraepithelial lesions, varies ethnogeographically. Population-specific data are required for vaccine cost-effectiveness assessment and type replacement monitoring. HPV was detected from 2,790 Chinese women (444 invasive cervical cancers [ICC], 772 cervical intraepithelial neoplasia [CIN] grade 3, 805 CIN2 and 769 CIN1. The attribution of each HPV type found in multiple-type infections was approximated by the fractional contribution approach. Multiple-type infection was common and correlated inversely with lesion severity (54.7% for CIN1, 48.7% for CIN2, 46.2% for CIN3, 27.5% for ICC). Vaccine covered high-risk types (HPV16/18) attributed to 59.5% of squamous cell carcinoma, 78.6% of adenocarcinoma, 35.9% of CIN3, 18.4% of CIN2 and 7.4% of CIN1. Distinct features compared to worldwide were a higher attribution of HPV52 and HPV58, and a much lower attribution of HPV45. Inclusion of HPV52 and HPV58 in future vaccines would provide the highest marginal increase in coverage with 11.7% for squamous cell carcinoma, 14.4% for CIN3, 22.6% for CIN2 and 17.7% for CIN1. The attribution of HPV types in southern China is different from elsewhere, which should be considered in prioritizing HPV types for vaccine and screening assay development. PMID- 21976213 TI - In this issue of Occupational Medicine. PMID- 21976214 TI - Cognitive impairment in older workers--a guide to assessment. PMID- 21976215 TI - Hidden impairments, the Equality Act and occupational physicians. PMID- 21976217 TI - Mirko Virius Harvest 1938. PMID- 21976218 TI - Hazard, risk and a bullet. PMID- 21976220 TI - Occupational hazard of rubber tapping. PMID- 21976221 TI - Plasma antibody profiles as diagnostic biomarkers for tuberculosis. AB - Two billion people are infected with Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), worldwide. Ten million to 20 million of the infected individuals develop disease per year. TB is a treatable disease, provided that it is diagnosed in a timely manner. The current TB diagnostic methods are subjective, inefficient, or not cost-effective. Antibody-based blood tests can be used efficiently and cost-effectively for TB diagnosis. A major challenge is that different TB patients generate antibodies against different antigens. Therefore, a multiplex immunoassay approach is needed. We have developed a multiplex panel of 28 M. tuberculosis antigen-coated microbeads. Plasma samples were obtained from over 300 pulmonary TB patients and healthy controls in a country where TB is endemic, Pakistan. Multiplex data were analyzed using computational tools by multivariate statistics, classification algorithms, and cluster analysis. The results of antibody profile-based detection, using 16 selected antigens, closely correlated with those of the sputum-based diagnostic methods (smear microscopy and culture) practiced in countries where TB is endemic. Multiplex microbead immunoassay had a sensitivity and specificity of approximately 90% and 80%, respectively. These antibody profiles could potentially be useful for the diagnosis of nonpulmonary TB, which accounts for approximately 20% of cases of disease. Since an automated, high-throughput version of this multiplex microbead immunoassay could analyze thousands of samples per day, it may be useful for the diagnosis of TB in millions of patients worldwide. PMID- 21976222 TI - Comparison of abortion and infection after experimental challenge of pregnant bison and cattle with Brucella abortus strain 2308. AB - A comparative study was conducted using data from naive bison (n = 45) and cattle (n = 46) from 8 and 6 studies, respectively, in which a standardized Brucella abortus strain 2308 experimental challenge was administered during midgestation. The incidence of abortion, fetal infection, uterine or mammary infection, or infection in maternal tissues after experimental challenge was greater (P < 0.05) in bison than in cattle. In animals that did abort, the time between experimental challenge and abortion was shorter (P < 0.05) for bison than for cattle. Brucella colonization of four target tissues and serologic responses on the standard tube agglutination test at the time of abortion did not differ (P > 0.05) between cattle and bison. The results of our study suggest that naive bison and cattle have similarities and differences after experimental exposure to a virulent B. abortus strain. Although our data suggest that bison may be more susceptible to infection with Brucella, some pathogenic characteristics of brucellosis were similar between bison and cattle. PMID- 21976223 TI - CCR8 signaling influences Toll-like receptor 4 responses in human macrophages in inflammatory diseases. AB - CCR8 immunity is generally associated with Th2 responses in allergic diseases. In this study, we demonstrate for the first time a pronounced attenuated influx of macrophages in ovalbumin (OVA)-challenged CCR8 knockout mice. To explore whether macrophages in human inflamed lung tissue also were CCR8 positive, human lung tissue from patients with chronic obstructive pulmonary disease (COPD) was evaluated. Indeed, CCR8 expression was pronounced in invading monocytes/macrophages from lungs of patients with Global Initiative for Obstructive Lung Disease (GOLD) stage IV COPD. Given this expression pattern, the functional role of CCR8 on human macrophages was evaluated in vitro. Human peripheral blood monocytes expressed low levels of CCR8, while macrophage colony stimulating factor (M-CSF)-derived human macrophages expressed significantly elevated surface levels of CCR8. Importantly, CCL1 directly regulated the expression of CD18 and CD49b and hence influenced the adhesion capacity of human macrophages. CCL1 drives chemotaxis in M-CSF-derived macrophages, and this could be completely inhibited by lipopolysaccharide (LPS). Whereas both CCL1 and LPS monotreatment inhibited spontaneous superoxide release in macrophages, CCL1 significantly induced superoxide release in the presence of LPS in a dose dependent manner. Finally, CCL1 induced production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) and could inhibit LPS-induced cytokine production in a dose-dependent manner. Our data demonstrate, for the first time, the presence of CCR8 on inflammatory macrophages in human COPD lung tissue. Importantly, the functional data from human macrophages suggest a potential cross talk between the CCR8 and the Toll like receptor 4 (TLR4) pathways, both of which are present in COPD patients. PMID- 21976225 TI - Development of a human-murine chimeric immunoglobulin M for use in the serological detection of human alphavirus antibodies. AB - Diagnosis of human alphaviral infections relies on serological techniques, such as the immunoglobulin M antibody capture-enzyme-linked immunosorbent assay (MAC ELISA). We have humanized the alphavirus broadly cross-reactive murine monoclonal antibody 1A4B-6 to create a reagent capable of replacing human positive sera in the MAC-ELISA for diagnosis of human alphaviral infections. PMID- 21976224 TI - Improved antimicrobial host defense in mice following poly-(1,6)-beta-D glucopyranosyl-(1,3)-beta-D-glucopyranose glucan treatment by a gender-dependent immune mechanism. AB - Clinical trials with biological modifiers targeting specific inflammatory mediators associated with severe sepsis have shown no or limited survival benefit. The approach taken in studies reported here was to limit the point source of intra-abdominal infection by potentiating innate immune function, thereby lessening the severity of sepsis and improving survival. Soluble beta glucans, glucose polymers of the fungal cell wall, have been shown to stimulate innate immune host defense in animal and human studies when administered prior to an infectious challenge. We evaluated the effects of poly-(1,6)-beta-d glucopyranosyl-(1,3)-beta-d-glucopyranose glucan (PGG glucan) on overall survival when administered intraperitoneally after the onset of polymicrobial infection by cecal ligation and puncture (CLP). Since gender-dependent differences in host immune response to infection have been reported, male and female mice were prospectively stratified for PGG glucan treatment. Outbred CD-1 mice were administered 10 mg/kg of body weight PGG glucan or the polysaccharide control, dextran, 1 h after CLP. Six hours after CLP, blood samples were obtained for cytokine measurements. Surprisingly, a gender-dependent effect on the response to PGG glucan was revealed. PGG glucan enhanced survival in female mice over a 10 day period, but survival in males was improved for only 24 h. In female mice, PGG glucan reduced interleukin-6 (IL-6) and IL-10 levels and reduced the bacterial burden in the liver. Ovariectomy abrogated the response to PGG glucan. Together, the translational potential of these findings is the indicated use of PGG glucan given locally, rather than intravenously, for improved source control during the management of sepsis. This therapy does not require prophylactic beta-glucan administration. PMID- 21976226 TI - Immunogenicity of Mannheimia haemolytica recombinant outer membrane proteins serotype 1-specific antigen, OmpA, OmpP2, and OmpD15. AB - We previously identified Mannheimia haemolytica outer membrane proteins (OMPs) that may be important immunogens by using immunoproteomic analyses. Genes for serotype 1-specific antigen (SSA-1), OmpA, OmpP2, and OmpD15 were cloned and expressed, and recombinant proteins were purified. Objective 1 of this study was to demonstrate immunogenicity of the four recombinant OMPs in mice and cattle. Objective 2 was to determine if the addition of individual recombinant OMPs or combinations of them would modify immune responsiveness of mice to the recombinant chimeric protein SAC89, containing the main epitope from M. haemolytica outer membrane lipoprotein PlpE and the neutralizing epitope of M. haemolytica leukotoxin. Mice vaccinated with recombinant OmpA (rOmpA), rSSA-1, rOmpD15, and rOmpP2 developed significant antibody responses to M. haemolytica outer membranes and to the homologous recombinant OMP. Cattle vaccinated with rOmpA and rSSA-1 developed significant antibodies to M. haemolytica outer membranes by day 28, whereas cattle vaccinated with rOmpD15 and rOmpP2 developed only minimal responses. Sera from cattle vaccinated with each of the recombinant proteins stimulated complement-mediated killing of the bacterium. Concurrent vaccination with SAC89 plus any of the four rOMPs singly resulted in increased endpoint anti-SAC89 titers, and for the SAC89/rSSA-1 vaccinees, the response was increased significantly. In contrast, the SAC89/P2/SSA-1 and SAC89/OmpA/P2/D15/SSA-1 combination vaccines resulted in significant decreases in anti-SAC89 antibodies compared to SAC89 vaccination alone. In conclusion, under the conditions of these experiments, vaccination of mice and cattle with rOmpA and rSSA-1 stimulated high antibody responses and may have protective vaccine potential. PMID- 21976227 TI - Phase I study evaluating the safety and pharmacokinetics of MDX-1303, a fully human monoclonal antibody against Bacillus anthracis protective antigen, in healthy volunteers. AB - MDX-1303 (Valortim) is a fully human monoclonal antibody (hMAb) with a high affinity for Bacillus anthracis protective antigen (PA). MDX-1303 binds to PA and interferes with the activity of the anthrax toxin; it was selected based on its superior functional activity in the toxin neutralization activity (TNA) assay. MDX-1303 has demonstrated efficacy in the postexposure and therapeutic settings in New Zealand White rabbits, cynomolgus monkeys, and African green monkeys. This phase I study sought to characterize the safety, tolerability, immunogenicity, and pharmacokinetics (PK)/pharmacodynamics (PD) of MDX-1303 in healthy human subjects. Cohorts of 3 to 10 subjects were administered MDX-1303 as either a single intravenous (i.v.) dose at dose levels of 0.3, 1, 3, 10, and 20 mg/kg of body weight or as a single intramuscular (i.m.) dose at 100 mg. Forty-six subjects were enrolled, and 16 (35%) of these subjects experienced one or more grade 1 adverse events considered to be related to treatment with MDX-1303. There were no grade 2 to 4 adverse events or serious adverse events (SAEs) considered to be related to treatment. The mean half-life of MDX-1303 ranged from 22 to 33 days across the i.v. administration cohorts and was approximately 32 days following i.m. administration. Systemic exposure following 100-mg i.m. administration was within the range of exposure following 1-mg/kg i.v. administration with a relative bioavailability of approximately 65%. MDX-1303 was generally well tolerated, and no anti-MDX-1303 antibodies were detected following a single dose. PMID- 21976228 TI - Special issue: 8th International Conference of the British Dyslexia Association. Editorial. PMID- 21976229 TI - The incidence of symptomatic malrotation post gastroschisis repair. AB - Gastroschisis is known to be associated with abnormal bowel rotation. Currently, the broadly accepted practice is not to perform Ladd's procedure routinely at the time of closure of gastroschisis defects. However the incidence of symptomatic malrotation and volvulus post gastroschisis repair is unknown; this incidence is important in view of the current practice of bedside gastroschisis closure. This study examined the incidence of symptomatic malrotation and volvulus following gastroschisis repair. METHOD: Patients who had undergone gastroschisis repair between 1999 and 2009 in any of 2 tertiary centers were identified using the Hospital Inpatient Enquiry system. The medical records were reviewed to obtain demographic data and postoperative outcomes. Patients were contacted for follow up. RESULTS: 128 patients were identified with a median postoperative follow-up of 4 years (range: 6 weeks to 12 years). Upper gastrointestinal (GI) contrast studies were performed in 30 patients (23.4%), 21 (16.4%) of whom showed evidence of malrotation. Malrotation was documented during the primary repair in 12 patients (9.4%); however Ladd's procedure was performed primarily in only 3 patients. 7 patients underwent Ladd's procedure in a second laparotomy for mechanical obstruction secondary to causes not related to malrotation and volvulus. A total of 29 patients (22.7%) had either operative or radiological evidence of malrotation. None of these patients developed volvulus after being followed for a median period of 4 years. CONCLUSION: Bedside gastroschisis closure without concomitant Ladd's procedure is a safe practice. None of the patients with documented malrotation developed volvulus post gastroschisis repair. PMID- 21976230 TI - The problematic Duhamel pouch in Hirschsprung's disease: manifestations and treatment. AB - PURPOSE: The Duhamel operation is commonly employed to treat Hirschsprung's disease (HD). We have seen a number of patients referred to our center with problems following a Duhamel procedure performed elsewhere, and have analyzed our experience with these children. METHODS: We reviewed 17 patients with Hirschsprung's disease who underwent a Duhamel procedure elsewhere, in whom we performed a redo pull-through for persistent symptoms of constipation, impaction, and enterocolitis. RESULTS: All patients (n=17) had constipation/impaction or enterocolitis, 9 of whom were soiling due to overflow incontinence. Biopsies of the pulled-through bowel found 6 patients with persistent aganglionic bowel and 2 patients with ganglion cells present but hypertrophic nerves, a finding we interpreted as "transition zone bowel". The remaining 9 patients without a pathological indication for reoperation had a mega Duhamel pouch. All patients underwent a redo operation: 8 via a posterior sagittal approach (7 with a laparotomy, 1 without) and 9 by a transanal, Swenson-type resection with a laparotomy. The posterior sagittal approach was used in cases with severe pelvic fibrosis considered unsuitable for a trans-anal operation. 15 patients were followed up postoperatively for longer than 2 months, 13 of whom now have voluntary bowel movements, including 8 who need a small dose of laxatives. 2 patients are still diverted. CONCLUSION: Although perhaps successful for many patients around the world, the Duhamel pull-through can leave patients with significant symptoms, including impaction and overflow incontinence. It is unclear why some patients with a Duhamel pouch do not empty well. Clearly, those patients with a mega Duhamel pouch suffer from impaction. These patients need to be detected, because reoperation with resection of the Duhamel pouch can dramatically improve their quality of life. PMID- 21976231 TI - Traumatic left lateral C2 epiphysiorhexis in a 3-year-old girl--a case report. PMID- 21976232 TI - Ischemic stroke after minor head trauma in children. PMID- 21976233 TI - Simultaneous measurement of benzo[a]pyrene-induced Pig-a and lacZ mutations, micronuclei and DNA adducts in MutaTM Mouse. AB - In this study we compared the response of the Pig-a gene mutation assay to that of the lacZ transgenic rodent mutation assay, and demonstrated that multiple endpoints can be measured in a 28-day repeat dose study. MutaTMMouse were dosed daily for 28 days with benzo[a]pyrene (BaP; 0, 25, 50 and 75 mg/kg body weight/day) by oral gavage. Micronucleus (MN) frequency was determined in reticulocytes (RETs) 48 hr following the last dose. 72 h following the last dose, mice were euthanized, and tissues (glandular stomach, small intestine, bone marrow and liver) were collected for lacZ mutation and DNA adduct analysis, and blood was evaluated for Pig-a mutants. BaP-derived DNA adducts were detected in all tissues examined and significant dose-dependent increases in mutant Pig-a phenotypes (i.e., RET(CD24-) and RBC (CD24-)) and lacZ mutants were observed. We estimate that mutagenic efficiency (i.e., rate of conversion of adducts into mutations) was much lower for Pig-a compared to lacZ, and speculate that this difference is likely explained by differences in repair capacity between the gene targets, and differences in the cell populations sampled for Pig-a versus lacZ. The BaP doubling doses for both gene targets, however, were comparable, suggesting that similar mechanisms are involved in the accumulation of gene mutations. Significant dose-related increases in % MN were also observed; however, the doubling dose was considerably higher for this endpoint. The similarity in dose response kinetics of Pig-a and lacZ provides further evidence for the mutational origin of glycosylphosphatidylinositol (GPI)-anchor deficiencies detected in the Pig-a assay. PMID- 21976234 TI - Traumatic subarachnoid hemorrhage, basal ganglia hematoma and ischemic stroke caused by a torn lenticulostriate artery. AB - Subarachnoid hemorrhage (SAH), basal ganglia hematoma (BGH) and ischemic stroke are common diseases with diverging therapies. The simultaneous occurrence of these diseases is rare and complicates the therapy. We report the case of a 30 year-old man with a ruptured lenticulostriate artery after traumatic brain injury that caused the combination of SAH, BGH and ischemic stroke and subsequent cerebral vasospasm. This rupture mimicked the pathophysiology and imaging appearance of aneurysmal SAH. The site of rupture was not secured by any treatment; however, hyperdynamic therapy and percutaneous transluminal angioplasty were feasible in this setting to prevent additional delayed neurological deficit. PMID- 21976235 TI - Expanding applications of deep brain stimulation: a potential therapeutic role in obesity and addiction management. AB - BACKGROUND: The indications for deep brain stimulation (DBS) are expanding, and the feasibility and efficacy of this surgical procedure in various neurologic and neuropsychiatric disorders continue to be tested. This review attempts to provide background and rationale for applying this therapeutic option to obesity and addiction. We review neural targets currently under clinical investigation for DBS-the hypothalamus and nucleus accumbens-in conditions such as cluster headache and obsessive-compulsive disorder. These brain regions have also been strongly implicated in obesity and addiction. These disorders are frequently refractory, with very high rates of weight regain or relapse, respectively, despite the best available treatments. METHODS: We performed a structured literature review of the animal studies of DBS, which revealed attenuation of food intake, increased metabolism, or decreased drug seeking. We also review the available radiologic evidence in humans, implicating the hypothalamus and nucleus in obesity and addiction. RESULTS: The available evidence of the promise of DBS in these conditions combined with significant medical need, support pursuing pilot studies and clinical trials of DBS in order to decrease the risk of dietary and drug relapse. CONCLUSIONS: Well-designed pilot studies and clinical trials enrolling carefully selected patients with obesity or addiction should be initiated. PMID- 21976236 TI - The usefulness of S100B, NSE, GFAP, NF-H, secretagogin and Hsp70 as a predictive biomarker of outcome in children with traumatic brain injury. AB - BACKGROUND: Predicting the long-term outcome after traumatic brain injury (TBI) is an important component of treatment strategy. Despite dramatically improved emergency management of TBI and apparent clinical recovery, most patients with TBI still may have long-term central nervous system (CNS) impairment. METHODS: Sixty-three patients with TBI were enrolled into the prospective study. Venous blood samples were taken at admission and every 24 h for a maximum of 6 consecutive days. Serum concentrations of the biomarkers S100B, neuron-specific enolase (NSE), GFAP, NF-H, secretagogin and Hsp70 were quantified immuno luminometrically or by enzyme-linked immunosorbent assay. The outcome was evaluated 6 months after TBI using the Glasgow Outcome Scale (GOS) in all patients. RESULTS: The S100B levels in patients with worse outcome (GOS 4 or death) were already significantly higher at D0 (p < 0.001; p = 0.002). NSE levels were significantly higher in patients who died or had worse outcomes (p < 0.001; p = 0.003). Patients who had worse outcomes (GOS) or died had higher GFAP values (p < 0.001; p < 0.001), but their dynamics were similar over the same period. NF H grew significantly faster in patients who had a worse GOS or died (p < 0.001; p = 0.001). CONCLUSIONS: Although further prospective study is warranted, these findings suggest that levels of biomarkers correlate with mortality and may be useful as predictors of outcome in children with TBI. PMID- 21976237 TI - Molecular basis of calcium binding by polyguluronate chains. Revising the egg-box model. AB - The egg-box model is the commonly accepted description of the calcium alginate/guluronate structure. It assumes that calcium ions are bound in the periodic chelation sites located between two polyuronate chains. This study was focused on elucidating the nature of interactions between calcium and polyuronates, responsible for the Ca(2+)-induced association of polyuronate chains in the aqueous solutions. Both molecular dynamics and semiempirical (ZINDO 1/Monte Carlo) methods were used for this purpose. Based on the obtained results, new structural models of Ca(2+)-polyguluronate complexes were proposed both for parallel and antiparallel pairing. Contrary to the classical egg-box model, Ca(2+) ions are coordinated by four carboxyl oxygens from two opposite carboxyl groups belonging to two different polyguluronate chains and, additionally, by four oxygen atoms belonging to water molecules. Such a coordination pattern can be interpreted as the result of competition between water molecules and carboxylic groups of polyguluronate for calcium ions. Other structural details (the network of hydrogen bonds, for instance) are close to those corresponding to the "shifted" egg-box model proposed by Braccini and Perez (Biomacromolecules 2001, 2, 1089) and remain in agreement with the experimental data. PMID- 21976239 TI - Progress in hematopoietic cell transplantation. PMID- 21976240 TI - Outcomes from unrelated donor hematopoietic stem cell transplantation. AB - BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) offers a curative treatment option for management of a variety of hematologic malignancies. While sibling donors have been the gold standard for adult patients in need of an HCT, not all patients have a suitable family donor. The availability of unrelated volunteer donor registries and alternative stem cell sources has expanded the wide application of this procedure. METHODS: PubMed and MEDLINE were searched for human trials and the English language from 2001 to 2011. Factors influencing transplantation outcomes involving unrelated donors over the last decade are discussed, and feasible alternative stem cell sources when a matched unrelated donor is not available are reviewed. RESULTS: HCT using a matched unrelated donor offers outcomes comparable to sibling HCT due to current molecular-based HLA typing and improvements in conditioning regimens and/or supportive care. The primary factor that contributes to improved outcome is the degree of donor-to recipient HLA matching. The selection of younger unrelated donors has also been associated with improved outcomes in HCT. Evidence supports the universal application of matched unrelated donors even in high-risk leukemia and/or older patients. In adult patients without a matched related donor, other promising options as stem cell source includes mismatched unrelated donors, umbilical cord blood units, and haploidentical donors. CONCLUSIONS: With current methodologies for molecular HLA typing and supportive care tools, outcomes of transplants with matched unrelated donors are comparable to those achieved with sibling donors. Alternative stem cell donors when a matched unrelated donor is not available are feasible expanding the stem cell donor pool. PMID- 21976241 TI - Umbilical cord blood transplantation for the treatment of hematologic malignancies. AB - BACKGROUND: The use of unrelated umbilical cord blood (UCB) has grown as an allogeneic source of hematopoietic cells for transplantation of patients with hematologic malignancies. As the number of UCB transplantation procedures has grown, an increasing number of publications have focused on disease-specific outcomes. METHODS: This review focuses on the outcome data following UCB transplantation in subsets of hematologic malignancies in which experience with this graft source is greater. RESULTS: Registry and single-institution reports regarding the outcomes of children and adults with acute leukemias after UCB transplantation include many patients, while data on the clinical outcomes of other leukemias are limited due in part to the small number of patients with these diseases. UCB is now routinely used as a source of hematopoietic stem cells (HSCs) in pediatric allogeneic transplantation when a suitable sibling donor is not available. Data also support the use of UCB as an alternative source of HSC for transplantation of patients with hematologic malignancies who lack a more conventional donor. Current data also support UCB for patients who require an allograft in the setting of prospective clinical trials. CONCLUSIONS: Along with safety and feasibility in UCB transplantation, continued study is needed that focuses on issues such as accelerating engraftment, extending access, ensuring quality, and examining outcomes in specific subgroups of patients. PMID- 21976242 TI - Reduced-intensity conditioning allogeneic hematopoietic cell transplantation in adults with acute myeloid leukemia. AB - BACKGROUND: Acute myeloid leukemia (AML), whether de novo or arising from antecedent hematologic disorders in elderly patients, is less likely to be curable with standard chemotherapy regimens used for younger patients. Allogeneic hematopoietic cell transplantation (allo-HCT) is currently the most efficient anti-leukemia treatment for AML and has shown a survival advantage in younger patients with intermediate- or poor-risk cytogenetics. METHODS: The authors review their experience as well as the published data regarding the role of reduced-intensity conditioning (RIC) allo-HCT in adults with AML. MEDLINE/PubMed and EMBASE/Ovid were searched, as well as reference lists of relevant articles, conference proceedings, and ongoing trial databases. RESULTS: Elderly patients with AML have a poor survival for all cytogenetics subgroups (except for acute promyelocytic leukemia) and higher rates of transplant-related mortality with myeloablative allo-HCT. RIC regimens have been shown to decrease procedure related toxicity and have emerged as an attractive treatment modality in AML patients not suitable for myeloablative conditioning regimens. While prospective data comparing outcomes of AML patients undergoing RIC allo-HCT vs conventional chemotherapy alone are not yet available, RIC allo-HCT is a reasonable option for high-risk older patients and for younger AML patients with medical comorbidities who achieve a first or subsequent remission. The application of RIC for patients with refractory disease or untreated relapse as well as the use of alternative donors should be considered within the context of clinical trials. CONCLUSIONS: RIC allo-HCT is a safe and effective treatment modality in high-risk elderly AML patients and in younger AML patients with medical comorbidities. PMID- 21976243 TI - Hematopoietic cell transplantation for lymphomas. AB - BACKGROUND: The heterogeneity of lymphomas results in numerous treatment options, including both autologous and allogeneic hematopoietic cell transplantation. However, the type of transplantation, the timing the procedure, and the selection of suitable patients for transplant continue to evolve. METHODS: We reviewed the current medical literature to provide a succinct synthesis for the most common types of lymphoma and the indications for transplantation. RESULTS: This review discusses the outcomes of autologous and allogeneic transplantation for patients with diffuse large B-cell lymphoma, follicular lymphoma, HIV-associated lymphomas, mantle cell lymphoma, T-cell lymphoma, and Hodgkin lymphoma. CONCLUSIONS: Each of these histologies differs in the indications and timing for transplantation. However, ongoing clinical trials support the continuing role of both autologous and allogeneic transplantation for lymphoma management. PMID- 21976244 TI - Advances in the autologous and allogeneic transplantation strategies for multiple myeloma. AB - BACKGROUND: Multiple myeloma is largely an incurable malignant plasma cell neoplasm; however, the landscape of its treatment is rapidly changing. METHODS: The recent literature on both autologous and allogeneic transplant approaches for multiple myeloma was reviewed. RESULTS: High-dose chemotherapy followed by autologous hematopoietic cell transplantation (HCT) remains an integral component of upfront treatment strategy, and the incorporation of novel immunomodulators and proteasome inhibitor to induction regimens improves response rates and increases overall survivals. Bortezomib and lenalidomide-based combination chemotherapy regimens have become the standard induction myeloma therapy. When myeloma patients proceed to transplant after novel combination regimens, their response rates are further improved. Despite these recent major improvements, myeloma remains incurable and long-term survival appears elusive. Due in part to a potential graft-vs-myeloma effect, allogeneic HCT is a potentially curative transplant option. However, initial attempts have been hampered by the high transplant-related mortality. With a reduction of toxicity, allogeneic transplant approaches with reduced-intensity conditioning have been utilized, although they are subject to continued disease progression and relapse following transplantation. Recent research efforts have shifted to the use of a tandem autologous-allogeneic HCT approach. The long-term follow-up of this new strategy is awaited. CONCLUSIONS: Recent advances in HCT have improved outcomes of patients with multiple myeloma. Ongoing research activity focuses on the strategies to improve outcomes of HCT by incorporation of tandem autologous allogeneic transplantation schema, novel conditioning regimens, and the use of consolidation and maintenance therapy. PMID- 21976245 TI - Graft-vs-host disease following allogeneic hematopoietic cell transplantation. AB - BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy with proven efficacy in the management of hematologic malignancies. However, it is complicated by the syndromes of acute and chronic graft-vs-host disease (GVHD). METHODS: A narrative review is provided to summarize major biologic insights into the pathogenesis of these immune-mediated disorders, as well as advances in diagnosis, classification, prevention, management, and allied supportive care with the aim of providing essential understanding for clinicians with or without subspecialty experience in the field of blood and marrow transplantation. RESULTS: Major scientific advances have contributed to enhanced understanding of the pathogenesis of these disorders, and clinical investigation has provided more effective preventive and therapeutic strategies for GVHD. However, since acute GVHD and chronic GVHD remain leading sources of transplantation-related morbidity and mortality, ongoing investigation is needed to develop new approaches to addressing these syndromes. CONCLUSIONS: The major challenge for future investigation will be to capitalize on biologic insights in order to develop novel strategies for the prevention and therapy of acute and chronic GVHD that will address the current shortcomings in existing therapeutic approaches. PMID- 21976247 TI - Heparin-like macromolecules for the modification of anticoagulant biomaterials. AB - A heparin-like structured macromolecule (HLSM) is synthesized by RAFT polymerization using carboxyl-terminated trithiocarbonate as the RAFT agent. The HLSM can be directly blended with PES in DMAC to prepare flat-sheet membrane by means of a liquid-liquid phase separation technique. The synthesized polymeric material retard blood clotting and the modified membrane exhibits good anticoagulant ability due to the existence of the important functional groups ?SO(3) H, ?COOH and ?OH. The anionic groups on the membrane surface may bind coagulation factors and thus improve anticoagulant ability. The results indicate that the HLSM has potential to improve the anticoagulant properties of biomaterials and to be applied in blood purification including hemodialysis and bioartificial liver supports. PMID- 21976248 TI - Sustained proliferation and resistance to apoptosis after a cytotoxic insult are early alterations in rat colon carcinogenesis. AB - To study the early alterations in carcinogenesis, we determined apoptosis and proliferation in rat mucin depleted foci (MDF), precancerous lesions in the colon under basal conditions and 24 h after treatment with 1,2-dimethylhydrazine (DMH), which induces apoptosis in the colon. Spontaneous apoptosis in MDF was higher than in normal mucosa (Apoptotic Index was 1.61 +/- 0.30 and 0.21 +/- 0.02 in MDF and normal mucosa, respectively, mean +/- SE, p < 0.05). DMH (30 and 75 mg/kg) increased apoptosis in both normal mucosa and MDF (up to 20 times higher compared to basal levels in normal mucosa, but only two times in MDF). MDF had a higher and deregulated pattern of proliferation along the crypt compared to normal mucosa. After DMH, proliferation in normal mucosa was significantly depressed, but it did not vary in MDF. Survivin-Birc5 regulating apoptosis and proliferation was significantly over-expressed (RT-qPCR and immunohistochemistry experiments) in MDF vs. normal mucosa, but did not vary in response to DMH. The expression of the pro-apoptotic protein Bak did not vary in normal mucosa and MDF. Since inflammation is present in MDF, which may hamper apoptosis, we studied the effect of pre-treatment with aspirin (600 ppm in the diet for 10 days). No significant effects of aspirin were observed. In conclusion, MDF had a higher spontaneous apoptosis and proliferation coupled with a reduced response to apoptotic stimuli from cytotoxic compounds. Survivin over-expression in MDF indicates that this is an early event in colon carcinogenesis and suggests that down-regulation of Survivin may represent a strategy for cancer prevention. PMID- 21976250 TI - Development of a portable graphite calorimeter for radiation dosimetry. AB - We developed and performance-tested a portable graphite calorimeter designed to measure the absolute dosimetry of various beams including heavy-ion beams, based on a flexible and convenient means of measurement. This measurement system is fully remote-controlled by the GPIB system. This system uses a digital PID (Proportional, Integral, Derivative) control method based on the LabVIEW software. It was possible to attain stable conditions in a shorter time by this system. The standard deviation of the measurements using the calorimeter was 0.79% at a dose rate of 0.8 Gy/min in 17 calorimeter runs for a (60)Co photon beam. The overall uncertainties for the absorbed dose to graphite and water of the (60)Co photon beam using the developed calorimeter were 0.89% and 1.35%, respectively. Estimations of the correction factors due to vacuum gaps, impurities in the core, the dose gradient and the radiation profile were included in the uncertainties. The absorbed doses to graphite and water irradiated by the (60)Co photon beam were compared with dosimetry measurements obtained using three ionization chambers. The absorbed doses to graphite and water estimated by the two dosimetry methods agreed within 0.1% and 0.3%, respectively. PMID- 21976249 TI - Changes in cerebellar functional connectivity and anatomical connectivity in schizophrenia: a combined resting-state functional MRI and diffusion tensor imaging study. AB - PURPOSE: To examine the functional and anatomical connectivity of the cerebellum and their relationship in schizophrenia through resting-state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI). MATERIALS AND METHODS: Ten subjects with schizophrenia and 10 healthy controls underwent resting-state fMRI and DTI. Left and right cerebellar seed regions were used in a voxel-wise functional connectivity analysis of the cerebellum. Fractional anisotropy (FA) was measured to assess white matter integrity of the middle cerebellar peduncle (MCP) and superior cerebellar peduncle (SCP). Differences in functional connectivity and FA values between the two groups were determined by two-sample t-tests. The relationship between functional connectivity and FA values in both groups were assessed using Pearson s correlation. RESULTS: Decreased functional connectivity to the left middle temporal gyrus, bilateral middle cingulate cortex, right paracentral lobule, right thalamus, and bilateral cerebellum were found in subjects with schizophrenia when compared to healthy controls; while decreased FA values in the left SCP were found in subjects with schizophrenia compared to healthy controls. Significant correlation was observed between the functional connectivity of the left cerebellum-right paracentral lobule and right cerebellum-right thalamus and the FA values of the MCP in healthy controls. CONCLUSION: Findings of this multi-modal imaging study support functional and anatomical connectivity abnormalities and the role of the cerebellum in schizophrenia. They also indicate the need for further investigation regarding the relationship between functional and anatomical connectivity and its role in neuropathophysiology. PMID- 21976251 TI - Evaluation of a Quasi-fractal Dimension to Enhance Breast Cancer Detection in X ray Mammograms using Support Vector Machine. AB - We previously introduced a quasi-fractal dimension (Q-FD) to enhance breast cancer detection in X-ray mammography. In the present study, we evaluated the usefulness of this image feature for differentiating between benign and malignant masses using a support vector machine (SVM) with various kernels. The kernel computes the inner product of the functions that embed the data into a feature space where the nonlinear pattern appears linear. Q-FD was calculated using the method previously reported from the database of X-ray mammograms produced by the Japan Society of Radiological Technology. In addition to Q-FD, the image features such as curvature (C) and eccentricity (E) were extracted. The conventional fractal dimension (C-FD) was also calculated using the box-counting method. First, we investigated the SVM performance in terms of accuracy, sensitivity and specificity in the task of differentiating between benign and malignant masses by taking 5 parameters (C, E, C-FD, Q-FD and age) as input features in SVM. When using the linear kernel, the best accuracy was obtained at a regularization parameter of 50. For the polynomial and radial basis function (RBF) kernels, the best accuracy was obtained when the degree of polynomial and the width of RBF were 1 and 1, respectively. The accuracies were 0.746+/-0.089, 0.731+/-0.095 and 0.734+/-0.086 for the linear, polynomial and RBF kernels, respectively, when using C, E, C-FD and age as input features in the SVM. When Q-FD was added to the above input features, the accuracies were significantly improved to 0.957+/ 0.045, 0.950+/-0.045 and 0.949+/-0.052 for the linear, polynomial and RBF kernels, respectively. These results suggest that Q-FD is effective for discriminating between benign and malignant masses and SVM is highly recommended as a classifier for its simple utilization and good performance, especially when the training set size is small. PMID- 21976252 TI - [Improvement of dose monitor system in rotational gantry for proton therapy at national cancer center hospital East]. AB - Quality assurance and quality control of delivered dose are important in proton therapy. The delivered proton dose is controlled using a dose monitor system which consists of two ionization chambers filled with free air. Response of the monitor for the delivered dose changes under the influence of temperature and pressure of surrounding air. In the dose monitor system at the National Cancer Center Hospital East, the monitor is near an X-tray tube which operates at a high temperature and is frequently used in every patient setup. Therefore the response of the dose monitor changes a lot with the temperature of the X-ray tube. In this report, temperature and pressure influence on the dose monitor was investigated in detail. Furthermore, a new method was presented to correct the monitor response using the real-time data of temperature and pressure at any time for each patient. This method improved the accuracy of delivered dose from 1% to 0.5%. PMID- 21976253 TI - Analytical design method of optimum ridge filters for wobbled and collimated proton beams. AB - A novel design method of ridge filters (RFs) has been developed for general proton beam lines which use a single-radius beam wobbling method. It can be applied to beam lines that transport both protons and carbon ions which are about three times longer than regular beam lines dedicated to protons. We designed an RF with an SOBP (spread-out Bragg peak) width of 60 mm in water for the 160-MeV proton beam of the HIMAC (Heavy Ion Medical Accelerator in Chiba) biology beam line using an existing model of the RF. Yet we observed a slope in the SOBP region when we used the RF. To elucidate the source of the slope, we have developed a new calculation model taking into account the geometry of the RF and a beam-limiting device. The source for the slope was found to be the large scattering effect of protons in the RF and beam restriction by a ring collimator (aperture diameter: 160 mm) placed just before the RF. When both fluence reduction by the scattering effect of protons in the RF and the beam-collimation effect are taken into account, proper RFs can be designed universally for a given beam line arrangement using the single-radius beam-wobbling method from the start without any trial-and-error process. This will serve to reduce the commissioning time of newly designed beam delivery systems. PMID- 21976254 TI - Verification of biological dose calculation for carbon ion therapy with a monte carlo method. AB - We developed a calculation technique to evaluate the biological dose distribution of heavy ion beams, and verified its reliability by comparison with experimental results. The calculation technique was developed by connecting two general purpose Monte Carlo codes. In order to evaluate the radiation quality and biological effect, the microdosimetric kinetic model was adopted. We estimated the distribution of physical dose and radiation quality for the carbon broad beam with experiments and with Monte Carlo calculations. Relative biological effectiveness (RBE) was estimated from radiation quality, and biological dose could be calculated as the product of the physical dose and the RBE. Our calculations showed good agreement with experiments, not only for the physical dose, but also for the dose-averaged lineal energy as an expression of radiation quality and therefore biological dose. This finding indicates that our calculation tool will be useful to estimate biological dose distribution in the design of heavy ion radiation facilities or for quality assurance in treatment planning. PMID- 21976255 TI - Research on radiation protection in the application of new technologies for proton and heavy ion radiotherapy. AB - Particle radiotherapy using proton and heavy ion beams has shown improved clinical results and is a promising cancer therapy which is expected to gradually spread in Japan. There are, however, no special regulations for radiotherapy treatment facilities. They have been operated under the same safety regulations as for a research facility using a research accelerator. Significantly high energy radiation is necessary for particle radiotherapy compared with conventional radiation therapy. The treatment facility, therefore, should have a large accelerator, which is installed in a room with a thick shield wall. Data on radiation protection for such high energy medical facilities is fragmentary and insufficient. In this study, we examined the necessity of other regulations for the safe operation of medical facilities for particle radiotherapy. First, we measured activation levels of the therapeutic devices and of patients. Next the safety level of the medical facility was evaluated from the viewpoint of radiation protection. We have confirmed the facilities can be safely operated by present regulations given in the Law Concerning Prevention from Radiation Hazards due to Radiation Isotopes, etc. or the Law for Health Protection and Medical Care. PMID- 21976256 TI - Multidimensional oriented solid-state NMR experiments enable the sequential assignment of uniformly 15N labeled integral membrane proteins in magnetically aligned lipid bilayers. AB - Oriented solid-state NMR is the most direct methodology to obtain the orientation of membrane proteins with respect to the lipid bilayer. The method consists of measuring (1)H-(15)N dipolar couplings (DC) and (15)N anisotropic chemical shifts (CSA) for membrane proteins that are uniformly aligned with respect to the membrane bilayer. A significant advantage of this approach is that tilt and azimuthal (rotational) angles of the protein domains can be directly derived from analytical expression of DC and CSA values, or, alternatively, obtained by refining protein structures using these values as harmonic restraints in simulated annealing calculations. The Achilles' heel of this approach is the lack of suitable experiments for sequential assignment of the amide resonances. In this Article, we present a new pulse sequence that integrates proton driven spin diffusion (PDSD) with sensitivity-enhanced PISEMA in a 3D experiment ([(1)H,(15)N]-SE-PISEMA-PDSD). The incorporation of 2D (15)N/(15)N spin diffusion experiments into this new 3D experiment leads to the complete and unambiguous assignment of the (15)N resonances. The feasibility of this approach is demonstrated for the membrane protein sarcolipin reconstituted in magnetically aligned lipid bicelles. Taken with low electric field probe technology, this approach will propel the determination of sequential assignment as well as structure and topology of larger integral membrane proteins in aligned lipid bilayers. PMID- 21976257 TI - Neurological Impairment Among Survivors of Intracerebral Hemorrhage: The FAST Trial. AB - BACKGROUND: Intracerebral hemorrhage (ICH) is the deadliest and most disabling form of stroke. Little is known about the causes of persistent neurological impairment among ICH survivors. METHODS: Factor seven for acute hemorrhagic stroke (FAST) was a randomized, multicenter, double-blind, placebo-controlled trial conducted at 122 sites in 22 countries. Neurological impairment was evaluated according to the NIHSS in all patients at hospital admission, and at days 1, 2, 3, 15 and day 90 after ICH onset. Multivariate stepwise logistic regression was applied to identify predictors of neurological impairment 90 days after hospital admission. RESULTS: A total of 821 patients were enrolled; 638 survivors were evaluated with the NIHSS at day 90. Mean NIHSS score at admission was 13.2 (SD 6.6), decreasing to 9.6 (SD 7.7) at day 15 and 5.1 (SD 5.5) at day 90. Twenty-five percent of patients had severe neurological impairment (NIHSS >= 15) at baseline compared to 6% of those alive at day 90. Neurological worsening within the first 72 h (defined as worsening of GCS of two or more points or increase in NIHSS score >= 4) predicted greater neurological impairment at day 90 in all models. A decrease of <10% in systolic blood pressure (SBP) within the first 24 h was significantly associated with less severe neurologic impairment compared to more severe reductions. CONCLUSION: Neurological deterioration within 24 h of ICH onset is a powerful determinant of persistent neurological impairment. Careful reduction of the SBP by 1-10% in the first 24 h may lower the risk. PMID- 21976260 TI - [DGRW updates on patient education and alcohol addiction]. PMID- 21976258 TI - Autonomic effects of intraventricular extension in intracerebral hemorrhage. AB - BACKGROUND: Autonomic dysfunction after stroke is common and relates to unfavorable outcome. The pathophysiology of autonomic impairment after intracerebral hemorrhage (ICH) is unknown. This study examined the relationship between intraventricular hemorrhage extension (IVH) and autonomic dysregulation after ICH. METHODS: We examined the autonomic modulation using the cross correlational time-sequence baroreflex sensitivity (BRS) in 68 ICH patients with and without IVH. Localization and extent of IVH based on the LeRoux score, hydrocephalus, hematoma volume, initial stroke severity and baseline demographic, clinical, and biochemical parameters were included in the analysis. RESULTS: IVH was present in 36 (52.9%) of patients. BRS was significantly lower in patients with IVH compared to those without IVH (BRS 2.35 vs. 3.5 ms/mmHg, P = 0.03). Patients with IVH including third and fourth ventricle had significantly lower BRS than patients with IVH in lateral ventricles (2.1 vs. 5.9 ms/mmg, P = 0.008) or patients without IVH (2.1 vs. 3.5 ms/mmHg, P = 0.003). There was no significant difference in BRS between patients with IVH in the lateral ventricles and patients without IVH (median BRS 5.9 vs. 3.5 ms/mmHg, P = 0.36). The amount of IVH in the third and fourth ventricle inversely correlated with decreased BRS (r = -0.43, P < 0.001). BRS did not correlate with initial hydrocephalus, hemorrhage volume, NIHSS score at admission, etiology of the ICH or parenchymal localization of the ICH. CONCLUSIONS: Hematoma extension to the third and fourth ventricle seems to cause profound autonomic dysregulation, possibly contributing to poor outcome. Patients with IVH in this location should be monitored vigorously to prevent and treat complications of autonomic failure. PMID- 21976261 TI - [DGRW-update: patient education]. AB - Patient education programmes, i. e. standardized, manualized, interactive group programmes aiming to increase self-management and empowerment, are a core element of medical rehabilitation for chronic conditions. In an update of the evidence of the effectiveness of patient education, its effectiveness was proven for a broad spectrum of chronic disorders, such as diabetes mellitus, chronic low back pain, rheumatoid arthritis, coronary heart disease, chronic heart failure, bronchial asthma, COPD, and cancer, as well as for the modification of health behaviours, such as diet and exercise. To sustain effects, aftercare interventions, such as support provided by phone, were found to be successful. Interventions targeted to particular patient groups according to gender, age, or migration background are also being developed more frequently. When evaluating educational interventions not only distal outcomes, such as quality of life and participation, should be used but also proximal outcomes such as self-management skills. A recent survey of patient education practice in medical rehabilitation revealed a continuing potential for optimization relative to manualization, evaluation and didactics. However, the dissemination of innovative programmes into rehabilitation routine presents a major challenge. PMID- 21976262 TI - [DGRW update: alcohol addiction]. AB - First, epidemiological data and socioeconomic consequences of alcohol addiction are summarized. Research findings, in particular in intervention and evaluation, from 2009-2011 in the field of alcohol addiction treatment are then discussed concerning their relevance for rehabilitation practice. The search was based on PubMed and PSYNDEX. The interventions most frequently evaluated and found most effective in alcohol addiction treatment are cognitive-behavioural interventions. Further topics dealt with are: pharmacological relapse prevention; technologically based therapies (e. g. e-therapy); systemic interventions; 12 steps; effectiveness of addiction treatment as confirmed in large-scale catamnestic studies; treatment of addiction and comorbidity; various subgroups (like elderly people and women); as well as other new and interesting developments such as rehab case management, dovetailing of medical and vocational interventions, stepped-care interventions, rehab management category groups as well as a new focus on individual treatment experiences and the pre-eminence of the therapeutic relationship. Finally, priority areas of future research are described. PMID- 21976263 TI - [Rehabilitee-management-categories (RMK)--results of the development phase and of the first clinical implementation in alcohol rehabilitation centres]. AB - BACKGROUND: Due to the introduction of lump sum reimbursement systems for acute care settings (DRGs), patient classification systems have been developed in Germany during the last 15 years to adapt a case-based lump sum system to the field of medical rehabilitation. The concept of Rehabilitee-Management-Categories (RMK), developed by the Charite - Universitatsmedizin Berlin, classifies rehabilitees primarily by their relevant impairments of activity and participation, as these factors mainly determine treatment needs and resources required in rehabilitation. It can, inter alia, be used to optimize the demand related allocation of treatment services in the rehabilitation centres as well as lead to more transparency in the allocation process. RMK results are reported on the example of inpatient rehabilitation of alcohol dependence. METHODS: Utilizing internationally established assessments, an RMK-assessment was developed that allows the assessment of rehab treatment needs of patients undergoing alcohol dependence rehabilitation. The RMK-assessment was completed by n=731 rehabilitees. Latent class analysis was applied to find groups of cases. To facilitate the RMK-patient classification a software-based algorithm was developed and implemented in 12 rehabilitation centres (implementation study). To validate the results of the first study phase, the data collected during implementation (n=1,533) was again analyzed using latent class analysis. Combined standardized and qualitative user surveys were conducted at the end of the implementation study. RESULTS: On the basis of 15 needs-related patient characteristics, 4 comparable case groups (AL-1 to AL-4) each were identified in 2 independent samples, groups that differed significantly in their degree of dependence-related, psychological and social impairment. The user survey confirmed the basic clinical plausibility of the 4 different case groups as well as the feasibility of the instruments applied in a rehabilitation setting. CONCLUSIONS: The RMK-concept offers a new approach for a demand-related patient classification in medical rehabilitation. The RMK-instruments allow a standardized initial assessment of impairment and treatment needs in alcohol rehabilitation and can hence be used for objective comparisons between rehabilitation centres. The results of the RMK-assessment provide relevant information about demand-related treatment requirements, which is a matter of great interest in the context of limited resources. Appropriate treatment requirements for the 4 RMK-case groups will be defined and verified in the next step of the RMK-concept. A financial evaluation of the RMK is possible in principal, will however require more extensive development, not least in order to model and evaluate the health-economic implications involved. PMID- 21976264 TI - [Occupational therapy in vocational rehabilitation of adults with mental illness]. AB - OBJECTIVE: This publication presents a study that analyses the effectiveness of client-oriented Occupational Therapy methods in Austria concerning improvement of the occupational performance of persons with mental illness. The central research issue had been the question how far client-centred OT treatment enables improvement in the occupational performance of mentally ill persons. METHODS: In order to answer the research question raised 150 persons in various vocational rehabilitation institutions were interviewed. The clients' recent performance and their satisfaction with their abilities were assessed in a pre-post design using the Canadian Occupational Performance Measure (COPM) and the Social and Occupational Functioning Assessment Scale (SOFAS). The focus of the Occupational Therapy interventions carried out had been on client orientation, on training of social competence and on activities of daily living. RESULTS: The intervention group's COPM scores, their COPM-satisfaction scores, as well as their SOFAS ratings of difference were significantly higher than those found for the control group. CONCLUSION: It could be shown that applying client-centred Occupational Therapy methods in vocational reintegration work can contribute considerably to improving the performance, satisfaction, quality of life, and social skills of persons with mental illness. PMID- 21976265 TI - [Development of an interprofessional train-the-trainer programme to implement shared decision-making in medical rehabilitation clinics]. AB - BACKGROUND AND AIMS: Until now, training programmes on shared decision-making (SDM) have been designed exclusively for medical decision-making and predominantly for physicians. How-ever, interprofessional treatment, such as in medical rehabilitation, is very important in the treatment of chronic diseases. This requires an extended understanding of shared decision-making. Therefore the aim of the study is to develop an interprofessional training (IPT) for implementation of shared decision-making (SDM) in rehabilitation clinics. METHODS: The needs and preferences of the persons undergoing rehabilitation were collected in 4 focus groups, with frequency of answers analyzed by means of inductive category formation. The providers' preferences and requirements concerning a training programme on shared decision-making were assessed through an expert survey and underwent a mainly descriptive-explorative evaluation as well as a partial content analysis. RESULTS: 36 patients took part in the focus groups. Besides the wish for more participation in treatment decisions, they expressed further needs, such as more time and respect. The -experts of the 4 clinics (n=34, rate of response: 71%) also assessed these aspects of the patient provider interaction as relevant. However, they saw the highest training need in the area of interdisciplinary team interactions. CONCLUSION: The interprofessional training programme "Fit for SDM" was developed on the basis of these results, and consists of 2 modules for the implementation of shared decision-making in medical rehabilitation. Module 1 focuses on external participation (provider-patient interaction), Module 2 on internal participation (team interaction). Module 2 was additionally used for preparing executives in their role as multipliers in the team. The training is currently being evaluated in a cluster-randomized multicentre study. PMID- 21976266 TI - [Cross-provider treatment and rehabilitation of children, youths, and young adults with mental problems: position paper on the convergence of books 8 and 9 of the German Social Code (abridged version)]. PMID- 21976267 TI - Supra-acetabular external fixation for pelvic fractures: a digital anatomical study. AB - Supra-acetabular external fixation is an important tool for pelvic fractures. Understanding the anatomical characteristics of anterior inferior iliac spine (AIIS) is crucial for the operation. Here, we analyzed the morphology of AIIS and adjacent structures via a digital measurement mode. One hundred and twenty normal pelvic computed tomography (CT) scans were converted into three-dimensional digital models and their parameters were measured by Geomagics software. We obtained the values of 13 important AIIS anatomical characteristics, which were the perpendicular distance of the anterior superior iliac spine(ASIS) and AIIS (PDASIS-AIIS), the perpendicular distance between the AIIS and superior pubic tubercle (PDAIIS-PT), the distance between the AIIS and anterior median line (HDAIIS-ML), the angle of the pin tract line and the horizontal plane (AHOR), the transverse diameter of AIIS (TD), and the minimum diameter of the pin tract plane (DMIN), etc. Among them, six parameters showed significant difference between male and female (PDASIS-AIIS: P =0.040, PDAIIS-PT: P = 0.001, HDAIIS-ML: P = 0.019, AHOR: P = 0.021, TD: P < 0.001, and DMIN: P = 0.003, respectively). These results provided references in locating pinning site for a safer and more accurate supra-acetabular external fixation and also suggested that gender difference should be considered during the surgery. PMID- 21976268 TI - The relative efficacy of aminoguanidine and pentoxifylline in modulating endotoxin-induced cardiac stress. AB - This study investigates the effect of aminoguanidine (AG), a selective inducible nitric oxide synthase (iNOS) inhibitor, and pentoxifylline (PTX), a tumour necrosis factor-alpha (TNF-alpha) inhibitor, on lipopolysaccharide (LPS)-induced cardiac stress. Rats were divided into four groups: group I served as a control, group II (LPS) received a single intraperitoneal injection of LPS (10 mg.kg(-1) ), group III (LPS+AG) and group IV (LPS+PTX) were injected with either AG (100 mg.kg(-1) ) or PTX (150 mg.kg(-1) ) intraperitoneally 10 days prior to LPS administration. Normalization of cardiac levels of nitrite/nitrate (NO(X) ), malondialdehyde (MDA), glutathione (GSH), heme oxygenase-1 (HO-1), glutathione peroxidase (GPx) and Na(+) , K(+) -ATPase activities was evident in the AG group. Both AG and PTX decreased the elevated serum TNF-alpha levels, the activities of lactate dehydrogenase (LDH), creatine kinase (CK) and cardiac myeloperoxidase (MPO). The levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and phosphocreatine (PCr) were enhanced following AG and PTX pretreatments. Calcium (Ca(2+) ) levels were altered, and the histopathological observations supported the described results. Conclusively, the study highlights the cardioprotective potential of AG and PTX with superior results from AG. These findings reveal the relative contribution of nitric oxide and TNF-alpha to oxidative stress and energy failure during endotoxemia. PMID- 21976269 TI - The cell biology of schistosomes: a window on the evolution of the early metazoa. AB - This review of schistosome cell biology has a dual purpose; its intent is to alert two separate research communities to the activities of the other. Schistosomes are by far and away the best-characterised platyhelminths, due to their medical and economic importance, but seem to be almost totally ignored by researchers on the free-living lower metazoans. Equally, in their enthusiasm for the parasitic way of life, schistosome researchers seldom pay attention to the work on free-living animals that could inform their molecular investigations. The publication of transcriptomes and/or genomes for Schistosoma mansoni and Schistosoma japonicum, the sponge Archimedon, the cnidarians Nematostella and Hydra and the planarian Schmidtea provide the raw material for comparisons. Apart from interrogation of the databases for molecular similarities, there have been differences in technical approach to these lower metazoans; widespread application of whole mount in situ hybridisation to Schmidtea contrasts with the application of targeted proteomics to schistosomes. Using schistosome cell biology as the template, the key topics of cell adhesion, development, signalling pathways, nerve and muscle, and epithelia, are reviewed, where possible interspersing comparisons with the sponge, cnidarian and planarian data. The biggest jump in the evolution of cellular capabilities appears to be in the transition from a diploblast to triploblast level of organisation associated with development of a mobile and plastic body form. PMID- 21976271 TI - Modifying emotion recognition deficits in body dysmorphic disorder: an experimental investigation. AB - BACKGROUND: Individuals with body dysmorphic disorder (BDD) are characterized by excessive concerns about perceived defects or flaws in their appearance, most commonly, facial features. Previous research has shown that BDD sufferers, relative to mentally healthy controls, are characterized by emotion recognition deficits (particularly a bias to misinterpret neutral facial expressions in a negative way). It remains an open question though whether these deficits can be modified through specific training programs. METHODS: To address this question, we evaluated emotion recognition among individuals with BDD (n = 34), individuals with a dermatological condition (n = 34), and mentally healthy control participants (n = 34) before and after a single-session emotion recognition training program. RESULTS: As expected, BDD participants were overall significantly worse in identifying neutral expressions, relative to the other groups, whereas no difference was obtained between the dermatology and control groups. Further, with respect to neutral and scared expressions, BDD participants improved significantly more in the training condition, relative to the nontraining condition. CONCLUSION: There is initial evidence that deficits in recognizing neutral and scared expressions can be normalized through a specific training program when evaluated immediately after the training session. It needs to be addressed in future research whether emotion recognition training programs can diminish these deficits on the long term, and how improved emotion recognition might be related to BDD's symptom reduction such as decreased avoidance behaviors in social situations. PMID- 21976270 TI - PTSD not an anxiety disorder? DSM committee proposal turns back the hands of time. PMID- 21976273 TI - New insights into the molecular mechanism of multiple synostoses syndrome (SYNS): mutation within the GDF5 knuckle epitope causes noggin-resistance. AB - Growth and differentiation factor 5 (GDF5), a member of the bone morphogenetic protein (BMP) family, is essential for cartilage, bone, and joint formation. Antagonists such as noggin counteract BMP signaling by covering the ligand's BMP type I (BMPRI) and type II (BMPRII, ActRII, ActRIIB) interaction sites. The mutation GDF5-S94N is located within the BMPRII interaction site, the so-called knuckle epitope, and was identified in patients suffering from multiple synostoses syndrome (SYNS). SYNS is characterized by progressive symphalangism, carpal/tarsal fusions, deafness and mild facial dysmorphism. Here we present a novel molecular mechanism of a GDF5 mutation affecting chondrogenesis and osteogenesis. GDF5-S94N exhibits impaired binding to BMPRII causing alleviated Smad and non-Smad signaling and reduced chondrogenic differentiation of ATDC5 cells. Surprisingly, chondrogenesis in mouse micromass cultures was strongly enhanced by GDF5-S94N. By using quantitative techniques (SPR, reporter gene assay, ALP assay, qPCR), we uncovered that this gain of function is caused by strongly reduced affinity of GDF5-S94N to the BMP/GDF antagonist noggin and the consequential lack of noggin inhibition. Thus, since noggin is upregulated during chondrogenic differentiation, GDF5-S94N exceeds the GDF5 action, which results in the phenotypic outcome of SYNS. The detailed molecular characterization of GDF5 S94N as a noggin-resistant growth factor illustrates the potential of GDF5 mutants in applications with defined therapeutical needs. PMID- 21976274 TI - Validation of the noninvasive assessment of central blood pressure by the SphygmoCor and Omron devices against the invasive catheter measurement. AB - BACKGROUND: To investigate the accuracy of the SphygmoCor and Omron HEM9000-AI devices in the estimation of central blood pressure (BP) in comparison with the simultaneous invasive catheter measurement. METHODS: The radial arterial pulse was sequentially recorded by the use of the Omron and SphygmoCor devices in 33 patients, with the calibration of the brachial oscillometric BP, to derive central BPs, which were also measured simultaneously with a catheter-based fluid filled manometer system. The procedure was repeated three times to obtain 99 pairs of noninvasive and invasive measurements. RESULTS: The noninvasive central systolic BP estimations were significantly (P < 0.001) associated with the invasive measurement at the ascending aorta, with a correlation coefficient of 0.91 and 0.90 for the SphygmoCor and Omron devices, respectively. However, both devices underestimated central systolic BP with a difference of -15 mm Hg (95% confidence interval (CI), -17 to -13 mm Hg, P < 0.001) for SphygmoCor and -2 mm Hg (95% CI, -4 to 0 mm Hg, P < 0.05) for Omron. In comparison with the invasive catheter measurement at the brachial artery, the oscillometric Omron device underestimated brachial systolic BP by -19 mm Hg (95% CI, -23 to -15 mm Hg, P < 0.001). CONCLUSIONS: Both devices underestimated central systolic BP, with a larger deviation by SphygmoCor. Nonetheless, these noninvasive estimations of central BP closely correlate with the invasive measurements, and can still be properly used, on the condition that device specific diagnostic thresholds become available. PMID- 21976275 TI - Central blood pressures are associated with left ventricular mass index among African-American adolescents. AB - BACKGROUND: There is a high burden of premature cardiovascular disease (CVD) among African Americans. Measures of central aortic blood pressure (CASP) and wave reflection are predictive of CVD risk in adults, but there is a paucity of data regarding the relation of these measures to target organ damage among adolescents. The objective of this study was to examine the relationship between CASP, central pulse pressure (CPP), and augmentation index (AI) with left ventricular mass index (LVMI). METHODS: A cohort of 120 African-American adolescents was examined. Study participants underwent measurement of peripheral blood pressure (BP) using auscultation, pulse wave analysis (PWA) for determination of CASP, CPP, and AI, and echocardiography for determination of LVMI. RESULTS: The cohort was 55% male, with mean BP 114/62 mm Hg, mean LVMI 36 g/m(2.7), mean CASP 94 mm Hg, mean CPP 31 mmHg, and mean AI was 0.5%. After adjustment for potential confounders, peripheral systolic BP (SBP) was significantly associated with LVMI (P = 0.008), but diastolic pressure was not (P = 0.887). The CASP and CPP were significantly associated with LVMI (P = 0.020 and 0.005, respectively). Peripheral SBP, CASP, and CPP had similar associations with respect to LVMI (r(2) = 0.26, 0. 26, and 0.27, respectively). CONCLUSION: Central BP is associated with LVMI among African-American adolescents, and these associations are similar to those seen with peripheral BP measurements. PMID- 21976276 TI - eNOS and caveolin-1 gene polymorphisms interaction and intima media thickness: a proof of concept study in ESRD patients. AB - BACKGROUND: Caveolae are a prominent microdomain in endothelial cells and appropriate localization in caveolae is fundamental for endothelial nitric oxide synthase (eNOS) activity. Since the Glu298Asp variant in the eNOS gene alters caveolar localization of the corresponding enzyme, we tested the interaction between this variant and the rs4730751 polymorphism of the caveolin-1 (CAV-1) gene as related to arterial remodeling in end-stage renal disease (ESRD) patients. METHODS: One hundred and thirty-three ethnically homogeneous ESRD patients underwent carotid ultrasonographic studies to measure intima-media thickness (IMT) and carotid cross-sectional area (CSA). Genotyping was performed by high-throughput allelic discrimination assays on real-time PCR. RESULTS: Arterial remodeling was associated to the number of G alleles of CAV-1 polymorphism, GG homozygotes displaying an IMT and a CSA that were, respectively, 16% and 21% higher than those in patients without the risk allele (P < 0.012). In multiple linear regression analyses including the CAV-1 and the eNOS polymorphisms and adjusting for classical risk factors and risk factors peculiar to ESRD both polymorphisms were independent correlates of IMT (CAV-1: beta = 0.20, P = 0.01; eNOS beta = 0.25, P = 0.001) and CSA (CAV-1: beta = 0.20, P = 0.01: eNOS beta = 0.13, P = 0.09). Furthermore, strong interactions emerged between the two polymorphisms for explaining the variability in IMT (P = 0.001) and in CSA (P = 0.038) in these patients. CONCLUSION: Overall these findings form preliminary evidence that disturbed interaction between CAV-1 and eNOS may be of relevance for arterial disease in ESRD and perhaps in other human diseases. PMID- 21976277 TI - Systolic blood pressure and adiposity: examination by race and gender in a nationally representative sample of young adults. AB - BACKGROUND: Adiposity, or more specifically, underlying body fat distribution, has been associated with systolic blood pressure (SBP), and it has been suggested that these associations vary between whites and blacks, as well as by gender. METHODS: Here, we use data from the National Longitudinal Study of Adolescent Health (Add Health), a US study of over 15,000 participants (median age 29.0 years), to characterize the associations between measures of body fat distribution-waist circumference (WC) and WC adjusted for body mass index (BMI) (WC(-bmi))-with SBP within white and black race and gender subgroups. RESULTS: Our findings suggest that, at lower levels of WC(-bmi), white women have significantly higher SBP as compared to black women, whereas black men have higher SBP than white men. Black women with WC(-bmi) >90 cm have higher SBP compared to white women with similar WC(-bmi), whereas among black and white men the associations are essentially similar across the full range of WC(-bmi). CONCLUSIONS: The present results suggest that associations among anthropometric measures of adiposity and blood pressure are nonlinear, and importantly, vary for whites and blacks by gender. In black women, SBP increased more as WC increased from low- to mid-range levels, whereas it was only at higher WC levels that black men exhibited higher SBP than white men. PMID- 21976278 TI - Impaired endothelial responses in apparently healthy young people associated with subclinical variation in blood pressure and cardiovascular phenotype. AB - BACKGROUND: A phenomenon of endothelial impairment, independent of classical cardiovascular risk factors, has been observed in young people. We identified subjects with persistently reduced, or declining, endothelial function during adolescence and early adulthood, without apparent cardiovascular risk, and investigated the clinical relevance of this finding. METHODS: Endothelial vasomotor responses were assessed by brachial artery flow-mediated dilatation (FMD) at age 15 years in 47 subjects (22 males) who returned for a repeated measurement at age 25. Subjects underwent quantification of left ventricular mass (LVM) and function by cardiovascular magnetic resonance, central arterial stiffness by applanation tonometry, and common carotid artery intima-media thickness using ultrasound on their visit at age 25. RESULTS: Individuals with low average FMD over 10-year period, although normotensive, had 5 mm Hg higher systolic blood pressure and, significantly greater LVM (73.48 +/- 7.73 vs. 56.25 +/- 9.54 g/m(2), P = 0.0001), carotid intima-media thickness (cIMT) (0.53 +/- 0.06 vs. 0.47 +/- 0.04 mm, P = 0.03), and pulse wave velocity (5.97 +/- 0.63 vs. 5.29 +/- 0.59 m/s, P = 0.02) than those with higher endothelial responses. Subjects with the greatest decline in FMD over 10 years had a significant increase in mean arterial pressure but similar cardiovascular phenotype. CONCLUSION: Persistently reduced, or declining, endothelial function during adolescence, in the absence of overt cardiovascular disease, is a sensitive early marker associated with subclinical changes in blood pressure (BP) and an adverse cardiovascular phenotype. The findings highlight the potential importance of endothelial responses during adolescence in primary prevention strategies for hypertension. PMID- 21976279 TI - Seasonal trend in the occurrence of preeclampsia and eclampsia in Texas. AB - BACKGROUND: The pathogenesis of preeclampsia remains poorly understood. Recent investigations have suggested that the incidence varies by season of conception and the season of delivery. A cross-sectional study was conducted to determine whether there was an association between the season of delivery and the prevalence of preeclampsia/eclampsia in Texas. METHODS: Retrospective analysis of hospital discharge records of 312,207 women who delivered in Texas in 2007 was performed. This statewide dataset was obtained from the Texas Department of State Health Services (Austin, TX). The season of admission for delivery was the independent variable: winter (December, January, February), spring (March, April, May), summer (June, July, August), and fall (September, October, November). The outcome was preeclampsia or eclampsia as defined by ICD-9-CM codes. Crude and adjusted prevalence odds ratios (OR) were calculated and reported with 95% confidence intervals (CI) and P values. The monthly prevalence of preeclampsia was also examined. RESULTS: Seasonal variation was minimal with the lowest prevalence detected in the fall (3.89%) and a peak of 4.1% in the winter. The highest monthly prevalence was found in January (4.4%). After adjusting for maternal age, race, and other potential confounders, women who were admitted in the fall for delivery were 6% less likely than women who were admitted in the winter to have preeclampsia: adjusted OR = 0.94, 95% CI: 0.89-0.99, P = 0.02). CONCLUSIONS: A weak protective association between delivering in the fall (vs. winter) and the prevalence of preeclampsia was noted in this analysis of a statewide hospital database. PMID- 21976280 TI - Maternal body mass index, height, and risks of preeclampsia. AB - BACKGROUND: There is an association between maternal body mass index (BMI) and preeclampsia, but if BMI has an effect on preeclampsia of all severities is debated. If there is an association between maternal height and preeclampsia of all severities is unknown. METHODS: In this population-based cohort study including 503,179 nulliparous women, we estimated risks of preeclampsia of different severity in short (<164 cm) and tall (>=172 cm) women, using women of average height (164-171 cm) as reference, and in underweight (BMI: <=18.4kg/m(2)), overweight (BMI: 25.0-29.9 kg/m(2)), obese class I (BMI: 30.0 34.9kg/m(2)) and obese class II-III (BMI: >=35.0 kg/m(2)) women, using women with normal weight (BMI: 18.5-24.9kg/m(2)) as reference. Severity of preeclampsia was classified as early (<32 weeks), moderately early (32-36 weeks), and late (>=37 weeks) preeclampsia, or severe preeclampsia and mild to moderate preeclampsia, as defined by diagnostic codes. RESULTS: Short women had increased risks of all types of preeclampsia, but especially of early disease (adjusted odds ratio (OR) 1.3; 95% confidence interval (CI) 1.2-1.5). The risks of all preeclampsia types increased with BMI, but seemed higher for milder than more severe types of preeclampsia. Obesity class II-III was associated with a four-fold increased risk of mild to moderate preeclampsia (adjusted OR 4.0; 95% CI 3.7-4.4). CONCLUSION: A short maternal stature and a high BMI increase risks of preeclampsia of all severities. The associations seem especially strong between short stature and severe types of preeclampsia, and high BMI and mild types of preeclampsia. PMID- 21976281 TI - Site-selective versus promiscuous A-to-I editing. AB - RNA editing by adenosine deamination is acting on polymerase II derived transcripts in all metazoans. Adenosine-to-inosine (A-to-I) editing is mediated by the adenosine deaminase that acts on RNA (ADAR) enzymes. Two types of adenosine to inosine (A-to-I) RNA editing have been defined: site selective and hyper-editing. Typically, in site selectively edited substrates, one or a few A to-I sites are edited in double-stranded RNA structures, frequently interrupted by single-stranded bulges and loops. Hyper-editing occurs in long stretches of duplex RNA where multiple adenosines are subjected to deamination. In this review, recent findings on editing within noncoding RNA as well as examples of site selective editing within coding regions are presented. We discuss how these two editing events have evolved and the structural differences between a site selective and hyper-edited substrate. PMID- 21976282 TI - SINEs. AB - Short interspersed elements (SINEs) are mobile genetic elements that invade the genomes of many eukaryotes. Since their discovery about 30 years ago, many gaps in our understanding of the biology and function of SINEs have been filled. This review summarizes the past and recent advances in the studies of SINEs. The structure and origin of SINEs as well as the processes involved in their amplification, transcription, RNA processing, reverse transcription, and integration of a SINE copy into the genome are considered. Then we focus on the significance of SINEs for the host genomes. While these genomic parasites can be deleterious to the cell, the long-term being in the genome has made SINEs a valuable source of genetic variation providing regulatory elements for gene expression, alternative splice sites, polyadenylation signals, and even functional RNA genes. PMID- 21976283 TI - Viruses and microRNAs: a toolbox for systematic analysis. AB - RNA silencing is emerging as a novel layer of regulation of virus-host interaction. Since individual small RNAs can probably repress dozens if not hundreds of target mRNA molecules, and transcripts, on the other hand, may be recognized by multiple regulatory small RNAs, a dense and complex interaction network of microRNAs (miRNAs) and their targets arises. A comprehensive analysis of miRNA functions thus not only requires systematic approaches employing high throughput technologies but also calls for the development of improved experimental technologies and a profound bioinformatic analysis. Integration of complementary approaches will enhance our understanding of the mutual regulation of virus and host. Focusing on herpesviruses, we here describe currently available technologies and summarize present results obtained by high-throughput approaches. These techniques can be broadly applied to other virus families and pathways employing other classes of small regulatory RNAs and therefore are powerful universal tools for research on virus-host interaction. PMID- 21976284 TI - Transfer RNA travels from the cytoplasm to organelles. AB - Transfer RNAs (tRNAs) encoded by the nuclear genome are surprisingly dynamic. Although tRNAs function in protein synthesis occurring on cytoplasmic ribosomes, tRNAs can transit from the cytoplasm to the nucleus and then again return to the cytoplasm by a process known as the tRNA retrograde process. Subsets of the cytoplasmic tRNAs are also imported into mitochondria and function in mitochondrial protein synthesis. The numbers of tRNA species that are imported into mitochondria differ among organisms, ranging from just a few to the entire set needed to decode mitochondrially encoded mRNAs. For some tRNAs, import is dependent on the mitochondrial protein import machinery, whereas the majority of tRNA mitochondrial import is independent of this machinery. Although cytoplasmic proteins and proteins located on the mitochondrial surface participating in the tRNA import process have been described for several organisms, the identity of these proteins differ among organisms. Likewise, the tRNA determinants required for mitochondrial import differ among tRNA species and organisms. Here, we present an overview and discuss the current state of knowledge regarding the mechanisms involved in the tRNA retrograde process and continue with an overview of tRNA import into mitochondria. Finally, we highlight areas of future research to understand the function and regulation of movement of tRNAs between the cytoplasm and organelles. PMID- 21976285 TI - Importance and key events of prokaryotic RNA decay: the ultimate fate of an RNA molecule. AB - RNAs are important effectors in the process of gene expression. In bacteria, constant adaptation to environmental demands is accompanied by a continual adjustment of transcripts' levels. The cellular concentration of a given RNA is the result of the balance between its synthesis and degradation. RNA degradation is a complex process encompassing multiple pathways. Ribonucleases (RNases) are the enzymes that directly process and degrade the transcripts, regulating their amounts. They are also important in quality control of RNAs by detecting and destroying defective molecules. The rate at which RNA decay occurs depends on the availability of ribonucleases and their specificities according to the sequence and/or the structural elements of the RNA molecule. Ribosome loading and the 5' phosphorylation status can also modulate the stability of transcripts. The wide diversity of RNases present in different microorganisms is another factor that conditions the pathways and mechanisms of RNA degradation. RNases are themselves carefully regulated by distinct mechanisms. Several other factors modulate RNA degradation, namely polyadenylation, which plays a multifunctional role in RNA metabolism. Additionally, small non-coding RNAs are crucial regulators of gene expression, and can directly modulate the stability of their mRNA targets. In many cases this regulation is dependent on Hfq, an RNA binding protein which can act in concert with polyadenylation enzymes and is often necessary for the activity of sRNAs. All of the above-mentioned aspects are discussed in the present review, which also highlights the principal differences between the RNA degradation pathways for the two main Gram-negative and Gram-positive bacterial models. PMID- 21976287 TI - Transfer RNA-derived fragments: origins, processing, and functions. AB - Deep sequencing approaches have revealed multiple types of small RNAs with known and unknown functions. In this review we focus on a recently identified group of small RNAs that are derived from transfer RNAs (tRNAs), tRNA fragments (tRFs). We review the mechanism of their processing and their functions in mammalian cells, and highlight points of possible cross-talk between tRFs and the canonical small RNA pathway characterized by small interfering RNAs (siRNAs), microRNAs (miRNAs), and Piwi-interacting RNAs (piRNAs). We also propose a nomenclature that is based on their processing characteristics. PMID- 21976288 TI - The maze of paramutation: a rough guide to the puzzling epigenetics of paramutation. AB - Epigenetic mechanisms maintain gene expression states through mitotic and sometimes meiotic cell divisions. Paramutation is an extreme example of epigenetic processes. Not only an established expression state is transmitted through meiosis to the following generations but also an information transfer occurs between alleles and leads to heritable changes in expression state. As a consequence the expression states can rapidly propagate in population, violating Mendelian genetics. Recent findings unraveled an essential role for siRNA dependent processes in paramutation. Despite significant progress, the overall picture is still puzzling and many important questions remain to be answered. PMID- 21976286 TI - Suppression of nonsense mutations as a therapeutic approach to treat genetic diseases. AB - Suppression therapy is a treatment strategy for genetic diseases caused by nonsense mutations. This therapeutic approach utilizes pharmacological agents that suppress translation termination at in-frame premature termination codons (PTCs) to restore translation of a full-length, functional polypeptide. The efficiency of various classes of compounds to suppress PTCs in mammalian cells is discussed along with the current limitations of this therapy. We also elaborate on approaches to improve the efficiency of suppression that include methods to enhance the effectiveness of current suppression drugs and the design or discovery of new, more effective suppression agents. Finally, we discuss the role of nonsense-mediated mRNA decay (NMD) in limiting the effectiveness of suppression therapy, and describe tactics that may allow the efficiency of NMD to be modulated in order to enhance suppression therapy. PMID- 21976289 TI - Transarterial chemoembolization in the treatment of patients with unresectable cholangiocarcinoma: Results and prognostic factors governing treatment success. AB - The aim of the study was to evaluate the effectiveness of transarterial chemoembolization (TACE) with four chemotherapeutic protocols in terms of local tumor control and survival of patients with unresectable cholangiocarcinoma (CCC) and to identify the prognostic factors governing treatment success. In the single centre study, 115 patients (mean ages = 60.4 years) with unresectable CCC were repeatedly treated with TACE. In total, 819 chemoembolization sessions were performed in 4 week intervals with a mean of 7.1 (range, 3-30) sessions per patient. The chemotherapeutic used was Mitomycin C only in 20.9% of patients, Gemcitabine only in 7%, Mitomycin C with Gemcitabine in 47% and combination of Gemcitabine, Mitomycin C and Cisplatin in 25.1%. Local tumor response was evaluated by MRI according to RECIST. Survival data were calculated according to the Kaplan-Meier method. Prognostic factors for patient's survival were evaluated using log-rank-test. The local tumor controls were: partial response 8.7%, stable disease 57.4% and progressive disease 33.9% of patients. The median and mean survival times from the start of TACE were 13 and 20.8 months. Survival rate from the start of TACE was 52% after 1-year, 29% after 2-years and 10% after 3-years. Initial tumor response, high tumor vascularity and Child-Pugh class A were statistically significant factors for patient's survival. No statistically significant difference between patients treated with different chemotherapy protocols was noted. In conclusion, TACE is a palliative and safe treatment option for patients with unresectable CCC. Child Pugh class B, tumor hypovascularity and initially progressive disease were poor prognostic factors for patient survival. PMID- 21976290 TI - Lowering the 'floor' of the SF-6D scoring algorithm using a lottery equivalent method. AB - This paper presents a new scoring algorithm for the SF-6D, one of the most popular preference-based health status measures. Previous SF-6D value sets have a minimum (a floor), which is substantially higher than the lowest value generated by the EQ-5D model. Our algorithm expands the range of SF-6D utility scores in such a way that the floor is significantly lowered. We obtain the wider range because of the use of a lottery equivalent method through which preferences from a representative sample of Spanish general population are elicited. PMID- 21976291 TI - Biological Activity of the Larval Secretion of Chilecomadia valdiviana. AB - The carpenter worm, Chilecomadia valdiviana (Lepidoptera: Cossidae), is a polyphagous insect native to Chile that is associated with trees and bushes, including economically important species such as eucalyptus, avocado, and apples. We used a Y-olfactometer to analyze the olfactory responses of larvae to conspecific larvae, hexane extracts of larvae, and synthetic samples of the major components present in the extract (i.e., (Z)-5,13-tetradecadienyl acetate, (Z)-5 tetradecenyl acetate, and dodecyl acetate). The results obtained provide empirical evidence that (Z)-5,13-tetradecadienyl acetate is used as an aggregation pheromone by the larvae. The results are discussed in view of the existing information. PMID- 21976292 TI - Systems strategies to support cancer screening in U.S. primary care practice. AB - BACKGROUND: Although systems strategies are effective in improving health care delivery, little is known about their use for cancer screening in U.S. primary care practice. METHODS: We assessed primary care physicians' (N = 2,475) use of systems strategies for breast, cervical, and colorectal cancer (CRC) screening in a national survey conducted in 2007. Systems strategies included patient and physician screening reminders, performance reports of screening rates, electronic medical records, implementation of in-practice guidelines, and use of nurse practitioners/physician assistants. We evaluated use of both patient and physician screening reminders with other strategies in separate models by screening type, adjusted for the effects of physician and practice characteristics with multivariate logistic regression. RESULTS: Fewer than 10% of physicians used a comprehensive set of systems strategies to support cancer screening; use was greater for mammography and Pap testing than for CRC screening. In adjusted analyses, performance reports of cancer screening rates, medical record type, and in-practice guidelines were associated with use of both patient and physician screening reminders for mammography, Pap testing, and CRC screening (P < 0.05). CONCLUSION: Despite evidence supporting use of systems strategies in primary care, few physicians report using a comprehensive set of strategies to support cancer screening. IMPACT: Current health policy initiatives underscore the importance of increased implementation of systems strategies in primary care to improve the use and quality of cancer screening in the United States. PMID- 21976294 TI - Evaluation of the mental foramen and accessory mental foramen in Turkish patients using cone-beam computed tomography images reconstructed from a volumetric rendering program. AB - This study determined the occurrence and location of the mental foramen (MF) and accessory mental foramen (AMF) in Turkish patients using cone-beam computed tomography (CBCT) with 3D-imaging software. CBCT scans of 386 sites in 193 (92 male, 101 female) patients were retrospectively analyzed to determine MF and AMF occurrence, sizes, and locations. Digital imaging and communications in medicine (DICOM) data were transferred to surface-rendering software to generate 3D images. Distances between the MF and AMF and from both foramina to the alveolar ridge and to the closest tooth were measured. Differences in AMF incidence by sex, side, and location were evaluated using chi-squared tests, and MF and AMF measurements were evaluated using Mann-Whitney U-tests. AMFs were observed in 6.5% of patients and were most commonly in an anteroinferior location. Mean AMF size did not differ significantly by sex or side [males: horizontal = 1.5 mm (1.0 2.4 mm), vertical = 1.4 mm (0.8-2.4 mm); females: horizontal = 1.5 mm (0.8-3 mm), vertical = 1.3 mm (0.8-2.1 mm); P > 0.05]. Males showed significantly greater mean vertical and horizontal MF dimensions compared with females [males: horizontal = 3.9 mm (1.0-7.0 mm), vertical = 3.6 mm (1.2-7.0 mm); females: horizontal = 3.5 mm (1.3-5.6 mm), vertical = 3.3 mm (0.8-5.8 mm); P < 0.05]. Awareness of the AMF is important to avoid mental nerve damage during surgical intervention and anesthetic applications. CBCT is useful for AMF detection, distributes less ionizing radiation, and allows 3D imaging. PMID- 21976293 TI - Cataract and ovarian carcinoma: is the vitamin D hypothesis alive? AB - BACKGROUND: The major health benefit of exposure to solar UV radiation is the production of vitamin D, which is implicated in protection against several human cancers, including ovarian carcinoma. On the other hand, solar UV radiation is a recognized risk factor for cataract. METHODS: This population-based case-control study of 709 women with primary invasive ovarian carcinoma and 1,101 controls examined the association of ovarian carcinoma risk with self-reported history of cataract as an indicator of high long-term exposure to UV radiation. ORs and 95% confidence intervals (CI) were estimated using multivariate logistic regression models. RESULTS: Among controls, older age (P < 0.0001), history of type 2 diabetes (P = 0.04), and skin cancer (P = 0.03) were significant cataract risk predictors. A history of cataract, reported by 14% of cases and 17% of controls, was significantly associated with a reduced ovarian carcinoma risk (OR = 0.6; 95% CI, 0.4-0.8; P = 0.002). No heterogeneity was observed by tumor histology, stage, grade, study site, body mass index, or other ovarian cancer risk factors (P > 0.16). CONCLUSION: These findings add indirect evidence to the hypothesis that lifetime vitamin D exposure may be inversely associated with risk of ovarian carcinoma. IMPACT: The study suggests some potential new avenues for research. Additional studies are needed to further investigate the potential behavioral and biologic factors that might influence association of cataract with ovarian cancer. PMID- 21976295 TI - [Medical rehabilitation of middle-aged insurants (55-plus): results of a qualitative study with rehab patients and rehab professionals]. AB - OBJECTIVE: Due to the demographic aging process of Germany's population, the development of morbidity and limited resources, a rethinking is needed in the fields of healthcare and social policy. The medical rehabilitation system will be of particular importance because of the increase of chronic and multiple illnesses in older age groups and the postponement of the retirement age. As the composition of rehabilitation patients will reflect broader demographic changes the question arises whether treatment plans of rehabilitation clinics will meet the demands and needs of older rehabilitation patients and which changes in rehabilitation processes might be required. METHODS: In 18 semi-structured focus groups, 62 rehabilitation patients with different indications aged over 55 years were asked about their needs, expectations and suggestions for improvement of the rehabilitation process. In contrast to previous quantitative research focusing on a comparison of rehabilitation needs and treatment offers of different age groups, only older rehabilitation patients were interviewed in this qualitative study. The results were discussed with health care experts in 3 multi disciplinary focus groups. The conversations were recorded, transcribed and analysed using the content analysis approach. RESULTS: The study showed a wide range of needs of rehabilitation patients concerning the treatment process. The desire for more patient-centred care, especially through improved provision of information and patient participation rights in therapeutic decisions, was an important aspect. A detailed individual plan of aftercare and following-up patients regularly can facilitate the integration of rehabilitation-related aims into everyday life and therefore enhance the sustainability of rehabilitation. According to the experts, many of the needs mentioned were comprehensible and legitimate. Under the present circumstances (restrictions of time and personnel, guidelines), however, implementation of the proposals made by the rehabilitation patients was considered difficult to realize. Rehabilitation patients and experts -agreed in that elements of occupational therapy should be expanded and transferred into real occupational setting and that intensified aftercare is needed. Contrary to our expectations, age-related aspects played a subordinate role according to both groups. Nevertheless, older rehabilitation patients saw a need for improvement in several areas of the rehabilitation process. Although the problems related to the rehabilitation process -generally may not be directly age related they might constitute a heavier burden for older patients. CONCLUSIONS: Optimizing various aspects of medical rehabilitation to reach sustainable outcomes in older rehabilitation patients appears to be necessary. Encouraging patients' individual responsibility for coping with the disease plays a key role in this process. Offering information tailored to patients' needs and provision of well-structured aftercare seem to be required especially for those older than 55. PMID- 21976297 TI - [Return to work--experiences and expectations of cancer patients during inpatient rehabilitation]. AB - AIMS: Returning to work after cancer frequently plays an important role for patients of working age. Accordingly, occupation and return to work are key issues for these patients during rehabilitation. So far there is only little empirical evidence from Germany concerning the expectations cancer patients in inpatient rehabilitation hold in relation to their return to work. Negative expectations may hamper returning to work. The context of rehabilitation offers the opportunity to work on potential problems to prepare a successful re-entry into employment. The aim of this study is to analyze the expectations of patients towards getting back to work and how helpful in this respect they estimate the work-related therapies provided during rehabilitation. Furthermore we asked whether professional support should be offered already before getting into inpatient rehabilitation and to what extent they have experienced that kind of help. METHODS: We conducted semi-structured qualitative interviews with 32 cancer patients who participated in inpatient cancer rehabilitation. All patients had been recruited within the same clinic. Interviews were analyzed based on Mayring's "Qualitative Content Analysis". RESULTS: The majority of the patients experienced positive reactions from their occupational environment after learning about the diagnosis. Most of them are optimistic to get help from colleagues and supervisors when returning to work. Prior to their rehabilitation stay 47% had received counseling on cancer and return to work from general practitioners or oncologists. Regarding the occupation-related offers during rehabilitation, the results suggest that women and men have different needs. Women consider them to be more helpful than men. CONCLUSIONS: The results indicate that after having received their diagnosis most cancer patients do not experience negative reactions from their work environment and consequently report few worries with regard to returning to work. The different views on work-related offers during rehabilitation indicate that the concepts of occupation-related therapies within cancer rehabilitation might be optimized by taking the different needs of male and female patients into account. PMID- 21976296 TI - [Somatic rehabilitation as a field of work for psychologists: results of a nationwide survey of structures and practice in orthopaedic and cardiac inpatient medical rehabilitation]. AB - OBJECTIVE: A detailed analysis of the present structural quality and practice of psychological services in inpatient medical rehabilitation facilities was conducted. The study was carried out for the indications chronic back pain and coronary heart disease. METHODS: A nationwide postal survey of psychological services in orthopaedic and cardiac inpatient rehabilitation facilities was carried out. RESULTS: Data from psychology departments of 169 orthopaedic and 75 cardiac inpatient rehabilitation facilities are available. In both indication areas an average of one psychologist is in charge of 100 patients. In the treatment of patients with chronic back pain and coronary heart disease, several methods of psychological assessment and a wide range of psychological interventions are being applied. On the whole, there are notable parallels between the psychological interventions provided to patients with chronic back pain and coronary heart disease. At the same time, however, there is considerable heterogeneity among rehabilitation facilities as to the psychological interventions carried out. DISCUSSION/CONCLUSION: The heterogeneity found reveals the low degree of standardization of psychological practice in medical rehabilitation of patients with chronic back pain or coronary heart disease. This emphasizes the need for developing and implementing recommendations or practice guidelines for psychological interventions. PMID- 21976298 TI - [Rehabilitation after occupational accidents in professional dancers: advice with due regard to dance specific aspects]. AB - The highly specialized occupation of professional dancers is a combination of sport and artistic expression. The exertion is only possible with a fully operative body. Although professional dancers may be compared with elite athletes and acute injuries frequently happen, dancers do not seem to be granted an appropriate therapy after accidents as compared with athletes. Although even minor injuries may potentially endanger the career of a professional dancer, physiotherapeutic or physical treatment methods are applied in every tenth case only. Alternative and holistic concepts such as Pilates or dance-specific re integration that proved successful in professional dancers, are used in even fewer instances. The aim of this study is to develop a rehabilitation concept for professional dancers focusing on dance-medicine aspects. It has been taken into account that the best physical outcomes are reflected in an optimized, holistic, dance-specific therapy and rehabilitation. Intensifying and exploiting dance specific methods of treatment can not only reduce costs in the end but can even contribute to reducing the duration of rehabilitation after injuries of dancers. Preconditions for realization of the rehabilitative model are a high qualification of all persons working in the rehabilitative field as well as a marked willingness to cooperate in the various dance fields. Both gender-specific and dance-style particularities are to be taken into account to ensure a successful rehabilitation. PMID- 21976299 TI - [Scientific monitoring of the visitation procedure in inpatient rehabilitation centres of the German statutory pension insurance fund--the "Visit II" Project]. AB - Visitation procedures are an established method of external quality assurance. They have been conducted for many years in the German statutory pension insurance's medical rehabilitation centres and have continuously been refined and standardized. The overall goal of the visitation procedure implemented by the German statutory pension fund is to ensure compliance with defined quality standards as well as information exchange and counselling of rehabilitation centres. In the context of advancing the visitation procedure in the German statutory pension funds' medical rehabilitation centres, the "Visit II" Project was initiated to evaluate the perspectives and expectations of the various professional groups involved in the visitations and to modify the materials used during visitations (documentation form and manual). Evaluation data from the rehabilitation centres visited in 2008 were gathered using both written surveys (utilization analysis) and telephone-based interviews with administration managers and chief physicians. The utilization analysis procedure was evaluated with regard to its methodological quality. In addition, the pension insurance physicians in charge of patient allocation during socio-medical assessment were surveyed with regard to potential needs for revision of the visitation procedure. Data collection was complemented by expert panels with auditors. Interviews with users as part of the formative evaluation of the visitation procedure showed positive results regarding acceptance and applicability of the visitations as well as of the utilization analysis procedures. Various suggestions were made with regard to modification and revision of the visitation materials, that could be implemented in many cases. Documentation forms were supplemented by current scientifically-based topics in rehabilitation (e. g., vocationally oriented measures), whereas items with minor relevance were skipped. The manual (for somatic indications) was thoroughly revised. The transparent presentation of visitation processes and visitation criteria has proven to be a useful basis for strengthening the cooperation between the statutory pension insurance funds and the rehabilitation centres. Moreover, it is a helpful tool for the systematic and continuous advancement of this complex method by including all parties involved. PMID- 21976300 TI - [Physical activity after rehabilitation treatment: the subjective influence of pain in terms of barrier or motivation]. AB - PURPOSE OF THIS STUDY: To examine the impact of the subjective health impairment due to pain, intention and planning on long-term physical activity. METHOD: A longitudinal questionnaire study with rehabilitation patients was performed over a time-span of more than 3 years. Data analyses were performed with binary logistic regressions. RESULTS: After controlling for social-cognitive variables subjective health impairment due to pain at the beginning of rehabilitation was a significant positive predictor of increased physical activity after rehabilitation. However, subjective health impairment due to pain 6 months after discharge was significantly negatively correlated with physical activity 3 years after rehabilitation. CONCLUSION: These findings suggest that subjective impairment due to pain should be considered when motivating people, e. g. by anticipating pain and possibilities for its improvement, respectively, or by coping planning on how to be physically active even in the face of pain. Especially during the time after rehabilitation patients may benefit from more help to manage pain. PMID- 21976301 TI - [Behaviour-orientated exercise therapy--initiating and maintaining a physically active lifestyle]. AB - BACKGROUND: The promotion of a physically active lifestyle has become an important issue in exercise therapy. Exercise-only interventions are frequently used for the rehabilitation of individuals with chronic diseases. These do indeed improve functional and physical performance, but they are not alone sufficient to initiate long lasting changes in physical-activity behaviour. Behaviour-related aspects are rarely integrated into exercise-therapy interventions. OBJECTIVE: Based on theories of health behaviour change, effective techniques for changing physical-activity behaviour in the context of exercise therapy will be identified. METHODOLOGY: The starting point is a theory-driven definition of individual behavioural determinants of physical activity and the identification of techniques for influencing the determinants. Subsequently, the potential of the techniques for enhancing physical activity is evaluated. The available evidence was reviewed on the basis of international reviews and control-group studies from the German rehabilitation setting. Finally, recommendations are offered for designing exercise-based interventions to promote participation in and adherence to physical activity. RESULTS: A total of 28 techniques for the promotion of physical activity behaviour were identified. An approach that proved particularly effective was self-monitoring of physical activity behaviour in a variety of combinations with other techniques, such as contracting, feedback, rewards, generating one's own varied exercise experience, action planning and barrier management. DISCUSSION: The integration of behaviour-related techniques in the context of exercise therapy interventions shows great promise as a means of initiating and promoting a physically active lifestyle. PMID- 21976302 TI - Assessing the localization of centrosomal proteins by PALM/STORM nanoscopy. AB - The structure of the centrosome was resolved by EM many years ago to reveal a pair of centrioles embedded in a dense network of proteins. More recently, the molecular composition of the centrosome was catalogued by mass spectroscopy and many novel components were identified. Determining precisely where a novel component localizes to within the centrosome remains a challenge, and until now it has required the use of immuno-EM. This technique is both time-consuming and unreliable, as it often fails due to problems with antigen accessibility. We have investigated the use of two nanoscopic techniques, photoactivated localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM), as alternative techniques for localizing centrosomal proteins. The localization of a known centrosomal component, the distal appendage protein Cep164 was investigated by direct STORM (dSTORM) and resolved with a high spatial resolution. We further validated the use of nanoscopic PALM imaging by showing that the previously uncharacterized centrosomal protein CCDC123 (Cep123) localizes to the distal appendages, forming ring-like structures with a diameter of 500 nm. Our results demonstrate that both PALM and STORM imaging have great potential as alternatives to immuno-EM. PMID- 21976303 TI - Self-assembled light-harvesting peptide nanotubes for mimicking natural photosynthesis. AB - Light-harvesting peptide nanotubes are synthesized by the self-assembly of diphenylalanine with THPP and platinum nanoparticles (nPt; see picture; TEOA = triethanolamine). The light-harvesting peptide nanotubes are suitable for mimicking photosynthesis because of their structure and electrochemical properties that are similar to the ones of photosystem I in natural photosynthesis. PMID- 21976304 TI - Long-term impact of adherence to oral bisphosphonates on osteoporotic fracture incidence. AB - Adherence to osteoporosis treatments is a critical parameter resulting in suboptimal effectiveness in real-life practice. The long-term effect of adherence on fracture risk has not been assessed. This was a retrospective study using provincial health insurance claims databases to assess the association between adherence to oral bisphosphonates (OBP) and incidence of osteoporotic fractures in all Ontario patients with osteoporosis between April 1996 and December 2009. Multivariate logistic regression models were used to assess the association between OBP adherence and fracture risk. Treatment duration was classified into 2 year intervals. Compliance was estimated with the medication possession ratio (MPR), and persistence was defined as the length of continuous therapy without a gap in refills >30 days. The study cohort was composed of 636,114 patients, among whom 36.1% were prescribed OBPs for 0 to 2 years, 19.7% for 2 to 4 years, 15.1% for 4 to 6 years, 12% for 6 to 8 years, 9.1% for 8 to 10 years, 6.1% for 10 to 12 years, and 1.9% for 12 to 14 years. Overall, the mean (SD) compliance for the cohort was 0.72 (0.30) with 53.5% of the patients having compliance >80% and 24.6% being persistent with treatment during the 14-year follow-up period. Significant associations between high adherence and reduced fracture risk over the entire 14-year period were observed; the overall odds ratio for categorical compliance (MPR >80% or MPR <=80%), continuous compliance, and persistence were 0.909 (95% confidence interval [CI] 0.893-0.925), 0.918 (95% CI 0.893-0.944), and 0.804 (95% CI 0.787-0.821), respectively. In conclusion, adherence to OBP in osteoporosis management is suboptimal in a real-life setting. A significant positive association exists between poor adherence and increased risk of osteoporotic fractures, which becomes augmented with longer treatment duration. PMID- 21976306 TI - Airborne microorganisms, endotoxin, and dust concentration in wood factories in Italy. AB - Exposure to biological agents and dusts occurs in homes and occupational environments and it is known to cause adverse health effects. There is limited information concerning the occupational exposure levels of airborne biohazard during wood processing, but this exposure is associated with a range of adverse health effects. Control of exposure to microbiological hazards and dust in woodworking is not easy. In fact, various types of wood are commonly used and they generate complex mixtures of dusts and biological agents with various health risks. The aim of this study was to investigate the concentration of dust, bacteria, and endotoxins encountered in six different wood factories. These people were exposed to between 0.05 and 12.00 mg inhalable dust m(-3) and between 0.40 and 6.93 ng inhalable endotoxins m(-3). Total bacteria concentrations in the air of the factories examined were within a range of 130-2000 CFU m(-3), the value of Gram negative was within a 0-164 CFU m(-3), and the concentration of Gram positive was within 1-104 CFU m(-3). In conclusion, people working in wood factories may be exposed to high levels of inhalable dust and endotoxins. PMID- 21976307 TI - Exposure to grain dust in Great Britain. AB - Airborne grain dust is a complex mixture of fragments of organic material from grain, plus mineral matter from soil, and possible insect, fungal, or bacterial contamination or their toxic products, such as endotoxin. In the 1990s, grain workers in Britain were frequently exposed to inhalable dust >10 mg.m(-3) (8 h), with particularly high exposures being found at terminals where grain was imported or exported and in drying operations (personal exposure typically approximately 20 mg.m(-3)). Since then, the industry has made substantial progress in improving the control of airborne dust through better-designed processes, increased automation, and an improved focus on product quality. We have used information from the published scientific literature and a small survey of industry representatives to estimate current exposure levels. These data suggest that current long-term exposure to inhalable dust for most workers is on average less than approximately 3 mg.m(-3), with perhaps 15-20% of individual personal exposures being >10 mg.m(-3). There are no published data from Britain on short-term exposure during cleaning and other tasks. We have estimated average levels for a range of tasks and judge that the highest levels, for example during some cleaning activities and certain process tasks such as loading and packing, are probably approximately10 mg.m(-3). Endotoxin levels were judged likely to be <104 EU m(-3) throughout the industry provided inhalable dust levels are <10 mg.m(-3). There are no published exposure data on mycotoxin, respirable crystalline silica, and mite contamination but these are not considered to present widespread problems in the British industry. Further research should be carried out to confirm these findings. PMID- 21976308 TI - Exposure and emissions monitoring during carbon nanofiber production--Part II: polycyclic aromatic hydrocarbons. AB - Production of carbon nanofibers and nanotubes (CNFs/CNTs) and their composite products is increasing globally. High-volume production may increase the exposure risks for workers who handle these materials. Though health effects data for CNFs/CNTs are limited, some studies raise serious health concerns. Given the uncertainty about their potential hazards, there is an immediate need for toxicity data and field studies to assess exposure to CNFs/CNTs. An extensive study was conducted at a facility that manufactures and processes CNFs. Filter, sorbent, cascade impactor, bulk, and microscopy samples, combined with direct reading instruments, provided complementary information on air contaminants. Samples were analyzed for organic and elemental carbon (OC and EC), metals, and polycyclic aromatic hydrocarbons (PAHs), with EC as a measure of CNFs. Transmission electron microscopy with energy-dispersive X-ray spectroscopy also was applied. Fine/ultrafine iron-rich soot, PAHs, and carbon monoxide were production byproducts. Direct-reading instrument results were reported previously [Evans DE et al. (Aerosol monitoring during carbon nanofiber production: mobile direct-reading sampling. Ann Occup Hyg 2010; 54:514-31)]. Results for time integrated samples are reported as companion papers in this issue. OC and EC, metals, and microscopy results are reported in Part I [Birch ME et al. (Exposure and emissions monitoring during carbon nanofiber production-Part I: elemental carbon and iron-soot aerosols. Ann Occup Hyg 2011; 55: 1016-36.)] whereas results for PAHs are reported here. Naphthalene and acenaphthylene were the dominant PAHs with average concentrations ranging from 115 to 336 MUg m(-3) and 35 to 84 MUg m( 3), respectively. Concentrations of other PAHs ranged from ~1 to 10 MUg m(-3). PMID- 21976310 TI - Comparing doctors' and nurses' accounts of how they provide emotional care for parents of children with acute lymphoblastic leukaemia. AB - OBJECTIVE: Despite the emphasis that communication skills training (CST) programmes place on attending to the emotional care of patients, evidence suggests that practitioners neglect this aspect of patient care. We describe and compare doctors' and nurses' accounts of managing the emotional care of parents of children with leukaemia, with the overall objective of examining how their accounts might inform training and policy. METHODS: Audio-recorded qualitative interviews with 30 doctors and nurses working in six UK paediatric oncology and haematology treatment centres were analysed interpretatively, drawing on the constant comparative method. RESULTS: Doctors' and nurses' descriptions of managing emotional care differed markedly. Doctors described reassuring parents through their ongoing clinical care of the child and by explaining the potentially curative nature of treatment. Doctors did not think they could reassure parents by eliciting and explicitly discussing parents' fears. In contrast, nurses relied on psychological skills and explicit discussion of parents' emotions to provide reassurance. Both doctors and nurses relied on each other to ensure that parents' emotional needs were met by the multidisciplinary team rather than by individual practitioners. CONCLUSION: Nurses' accounts of providing emotional care resembled the emphasis on explicit emotional talk in CST. However, doctors' accounts indicated that they provided emotional care in ways that diverged markedly from expectations in CST but that were more consistent with their biomedical and authoritative role in patient care. These findings may have implications for CST in future revisions of guidelines, but work is first needed to explore parents' perspectives on emotional care. PMID- 21976311 TI - Unique variation of the axillary arch muscle discovered during dissection could explain neurologic symptoms in the living patient. PMID- 21976309 TI - Combining a job-exposure matrix with exposure measurements to assess occupational exposure to benzene in a population cohort in shanghai, china. AB - BACKGROUND: Generic job-exposure matrices (JEMs) are often used in population based epidemiologic studies to assess occupational risk factors when only the job and industry information of each subject is available. JEM ratings are often based on professional judgment, are usually ordinal or semi-quantitative, and often do not account for changes in exposure over time. We present an empirical Bayesian framework that combines ordinal subjective JEM ratings with benzene measurements. Our aim was to better discriminate between job, industry, and time differences in exposure levels compared to using a JEM alone. METHODS: We combined 63 221 short-term area air measurements of benzene exposure (1954-2000) collected during routine health and safety inspections in Shanghai, China, with independently developed JEM intensity ratings for each job and industry using a mixed-effects model. The fixed-effects terms included the JEM intensity ratings for job and industry (both ordinal, 0-3) and a time trend that we incorporated as a b-spline. The random-effects terms included job (n = 33) and industry nested within job (n = 399). We predicted the benzene concentration in two ways: (i) a calibrated JEM estimate was calculated using the fixed-effects model parameters for calendar year and JEM intensity ratings; (ii) a job-/industry-specific estimate was calculated using the fixed-effects model parameters and the best linear unbiased predictors from the random effects for job and industry using an empirical Bayes estimation procedure. Finally, we applied the predicted benzene exposures to a prospective population-based cohort of women in Shanghai, China (n = 74 942). RESULTS: Exposure levels were 13 times higher in 1965 than in 2000 and declined at a rate that varied from 4 to 15% per year from 1965 to 1985, followed by a small peak in the mid-1990s. The job-/industry-specific estimates had greater differences between exposure levels than the calibrated JEM estimates (97.5th percentile/2.5th percentile exposure level, (B)(G)R(95)(B): 20.4 versus 3.0, respectively). The calibrated JEM and job-/industry-specific estimates were moderately correlated in any given year (Pearson correlation, r(p) = 0.58). We classified only those jobs and industries with a job or industry JEM exposure probability rating of 3 (>50% of workers exposed) as exposed. As a result, 14.8% of the subjects and 8.7% of the employed person-years in the study population were classified as benzene exposed. The cumulative exposure metrics based on the calibrated JEM and job-/industry-specific estimates were highly correlated (r(p) = 0.88). CONCLUSIONS: We provide a useful framework for combining quantitative exposure data with expert-based exposure ratings in population-based studies that maximized the information from both sources. Our framework calibrated the ratings to a concentration scale between ratings and across time and provided a mechanism to estimate exposure when a job/industry group reported by a subject was not represented in the exposure database. It also allowed the job/industry groups' exposure levels to deviate from the pooled average for their respective JEM intensity ratings. PMID- 21976312 TI - Polarity-switching electrochemical sensor for specific detection of single nucleotide mismatches. PMID- 21976314 TI - Nonlinear displacement of ventral stress fibers under externally applied lateral force by an atomic force microscope. AB - Actin-based stress fibers (SFs) have fundamental importance in the maintenance of mechanical stability of living cells. Several in vitro measurements of their elastic properties have therefore been made, but direct mechanical manipulation of individual SFs in vivo for the determination of their mechanical properties has not been attempted. No less important is a search for the possible formation of a global mechanical network involving SFs and other intracellular filamentous components. In this article, we present an application of atomic force microscopy to probe into a live cell and laterally push selected SFs in a fibroblast cells (VNOf 06 fibroblast-like cells derived from rat vomeronasal tissue) transfected with a green fluorescent protein-beta-actin gene. The transfected cells were transferred to a serum-depleted medium before the atomic force microscope manipulation. The lateral displacement of the SFs under a point loading condition recorded on a fluorescence microscope revealed both linear and nonlinear displacements against the contour distance from the point of force loading. The nonlinear displacements of the SFs were attributed to their association with a cortical actomyosin-cell membrane complex that effectively pulled them back as a 2D thin plate. PMID- 21976315 TI - Bevacizumab treatment for advanced breast cancer. AB - Significant advances in the treatment of patients with breast cancer have been made in the past 10 years. The current systemic treatment of breast cancer is characterized by the discovery of multiple cancer targets leading to treatments that are more sophisticated and specific than conventional cytotoxic chemotherapy. Two classes of compounds that have helped improve clinical outcomes are small molecules and monoclonal antibodies targeting specific tyrosine kinase receptors. Many novel targets have been discovered, and parallel multiple approaches to anticancer therapy have recently emerged from the literature. One promising strategy is targeting the proangiogenic vascular endothelial growth factors (VEGFs), either by ligand sequestration (preventing VEGF receptor binding) or inhibiting downstream receptor signaling. Bevacizumab, a monoclonal antibody directed against VEGF, has been shown to improve the efficacy of taxanes in frontline treatment of patients with metastatic breast cancer. This review outlines the most promising breast cancer studies using bevacizumab combined with traditional cytotoxic agents in advanced breast cancer. In addition, we discuss the current indications reviewed by the Oncologic Drug Advisory Committee and define our vision of how the benefit of patient clinical trials should be measured. PMID- 21976316 TI - The accuracy of probabilistic versus temporal clinician prediction of survival for patients with advanced cancer: a preliminary report. AB - Clinicians have limited accuracy in the prediction of patient survival. We assessed the accuracy of probabilistic clinician prediction of survival (CPS) and temporal CPS for advanced cancer patients admitted to our acute palliative care unit, and identified factors associated with CPS accuracy. Eight physicians and 20 nurses provided their estimation of survival on admission by (a) the temporal approach, "What is the approximate survival for this patient (in days)?" and (b) the probabilistic approach, "What is the approximate probability that this patient will be alive (0%-100%)?" for >=24 hours, 48 hours, 1 week, 2 weeks, 1 month, 3 months, and 6 months. We also collected patient and clinician demographics. Among 151 patients, the median age was 58 years, 95 (63%) were female, and 138 (81%) had solid tumors. The median overall survival time was 12 days. The median temporal CPS was 14 days for physicians and 20 days for nurses. Physicians were more accurate than nurses. A higher accuracy of temporal physician CPS was associated with older patient age. Probabilistic CPS was significantly more accurate than temporal CPS for both physicians and nurses, although this analysis was limited by the different criteria for determining accuracy. With the probabilistic approach, nurses were significantly more accurate at predicting survival at 24 hours and 48 hours, whereas physicians were significantly more accurate at predicting survival at 6 months. The probabilistic approach was associated with high accuracy and has practical implications. PMID- 21976317 TI - Bone mineral density loss in relation to the final menstrual period in a multiethnic cohort: results from the Study of Women's Health Across the Nation (SWAN). AB - The objective of this study was to describe the time of onset and offset of bone mineral density (BMD) loss relative to the date of the final menstrual period (FMP); the rate and amount of BMD decline during the 5 years before and the 5 years after the FMP; and the independent associations between age at FMP, body mass index (BMI), and race/ethnicity with rates of BMD loss during this time interval. The sample included 242 African American, 384 white, 117 Chinese, and 119 Japanese women, pre- or early perimenopausal at baseline, who had experienced their FMP and for whom an FMP date could be determined. Loess-smoothed curves showed that BMD loss began 1 year before the FMP and decelerated (but did not cease) 2 years after the FMP, at both the lumbar spine (LS) and femoral neck (FN) sites. Piecewise, linear, mixed-effects regression models demonstrated that during the 10-year observation period, at each bone site, the rates and cumulative amounts of bone loss were greatest from 1 year before through 2 years after the FMP, termed the transmenopause. Postmenopausal loss rates, those occurring between 2 and 5 years after the FMP, were less than those observed during transmenopause. Cumulative, 10-year LS BMD loss was 10.6%; 7.38% was lost during the transmenopause. Cumulative FN loss was 9.1%; 5.8% was lost during the transmenopause. Greater BMI and African American heritage were related to slower loss rates, whereas the opposite was true of Japanese and Chinese ancestry. PMID- 21976320 TI - A nation at risk for wider health disparities. PMID- 21976318 TI - Generation of Rab-based transgenic lines for in vivo studies of endosome biology in zebrafish. AB - The Rab family of small GTPases function as molecular switches regulating membrane and protein trafficking. Individual Rab isoforms define and are required for specific endosomal compartments. To facilitate in vivo investigation of specific Rab proteins, and endosome biology in general, we have generated transgenic zebrafish lines to mark and manipulate Rab proteins. We also developed software to track and quantify endosome dynamics within time-lapse movies. The established transgenic lines ubiquitously express EGFP fusions of Rab5c (early endosomes), Rab11a (recycling endosomes), and Rab7 (late endosomes) to study localization and dynamics during development. Additionally, we generated UAS based transgenic lines expressing constitutive active (CA) and dominant-negative (DN) versions for each of these Rab proteins. Predicted localization and functional consequences for each line were verified through a variety of assays, including lipophilic dye uptake and Crumbs2a localization. In summary, we have established a toolset for in vivo analyses of endosome dynamics and functions. PMID- 21976321 TI - 'Super committee' looks to health for savings to reduce deficits. AB - But, as with health care reform, Democrats and Republicans face off across a wide philosophical gulf. PMID- 21976322 TI - Reducing racial and ethnic disparities: the action plan from the department of health and human services. AB - The Department of Health and Human Services (HHS) recently unveiled the most comprehensive federal commitment yet to reducing racial and ethnic health disparities. The 2011 HHS Action Plan to Reduce Racial and Ethnic Health Disparities not only responds to advice previously offered by stakeholders around the nation, but it also capitalizes on new and unprecedented opportunities in the Affordable Care Act of 2010 to benefit diverse communities. The Action Plan advances five major goals: transforming health care; strengthening the infrastructure and workforce of the nation's health and human services; advancing Americans' health and well-being; promoting scientific knowledge and innovation; and upholding the accountability of HHS for making demonstrable progress. By mobilizing HHS around these goals, the Action Plan moves the country closer to realizing the vision of a nation free of disparities in health and health care. PMID- 21976323 TI - Health reform holds both risks and rewards for safety-net providers and racially and ethnically diverse patients. AB - The Affordable Care Act of 2010 creates both opportunities and risks for safety net providers in caring for low-income, diverse patients. New funding for health centers; support for coordinated, patient-centered care; and expansion of the primary care workforce are some of the opportunities that potentially strengthen the safety net. However, declining payments to safety-net hospitals, existing financial hardships, and shifts in the health care marketplace may intensify competition, thwart the ability to innovate, and endanger the financial viability of safety-net providers. Support of state and local governments, as well as philanthropies, will be crucial to helping safety-net providers transition to the new health care environment and to preventing the unintended erosion of the safety net for racially and ethnically diverse populations. PMID- 21976324 TI - Quality improvement efforts under health reform: how to ensure that they help reduce disparities--not increase them. AB - Despite persistent evidence of continued racial and ethnic disparities in health care, little explicit attention has been paid to how quality improvement activities might affect disparities. As the nation focuses on the practical realities of implementing health care reform and concurrent quality improvement provisions under the Affordable Care Act of 2010, it is important to recognize that overall improvements in the US health care system might not automatically benefit all segments of the population equally. In this article we highlight challenges to ensuring that quality improvement efforts reduce racial and ethnic disparities. These include making certain that quality improvement efforts measure disparities and improvements in them, notwithstanding providers' reputational concerns; that such efforts not create perverse incentives for providers to avoid serving minority patients; that they be applied to institutions where minority patients are most likely to receive care; and that they fully engage minority patients despite language or other barriers. To assist in these efforts, we argue for the development of disparities impact assessments to measure the effect that the Affordable Care Act's quality provisions will have on reducing disparities. PMID- 21976325 TI - Understanding disparities in health care access--and reducing them--through a focus on public health. AB - Attempts to explain disparities in access to health care faced by racial and ethnic minorities and other underserved populations often focus on individual level factors such as demographics, personal health beliefs, and health insurance status. This article proposes an examination of these disparities-and an effort to redress them-through the lens of public health. Public health agencies can link people to needed services such as immunizations, testing, and treatment; ensure the availability of health care; ensure the competency of the public health and personal health care workforce; and evaluate the effectiveness, accessibility, and quality of personal and population-based services. Approaching disparities through a public health framework can provide the foundation for developing more robust evidence to inform additional policies for improving access and reducing disparities. PMID- 21976326 TI - Where health disparities begin: the role of social and economic determinants--and why current policies may make matters worse. AB - Health disparities by racial or ethnic group or by income or education are only partly explained by disparities in medical care. Inadequate education and living conditions-ranging from low income to the unhealthy characteristics of neighborhoods and communities-can harm health through complex pathways. Meaningful progress in narrowing health disparities is unlikely without addressing these root causes. Policies on education, child care, jobs, community and economic revitalization, housing, transportation, and land use bear on these root causes and have implications for health and medical spending. A shortsighted political focus on reducing spending in these areas could actually increase medical costs by magnifying disease burden and widening health disparities. PMID- 21976327 TI - Awareness of racial and ethnic health disparities has improved only modestly over a decade. AB - Documented disparities exist in the United States between the majority white population and various racial and ethnic minority populations on several health and health care indicators, including access to and quality of care, disease prevalence, infant mortality, and life expectancy. However, awareness of these disparities-a necessary first step toward changing behavior and compelling action remains limited. Our survey of 3,159 adults age eighteen or older found that 59 percent of Americans in 2010 were aware of racial and ethnic disparities that disproportionately affect African Americans and Hispanics or Latinos. That number represents a modest increase over the 55 percent recorded in a 1999 survey. Meanwhile, in our survey, 89 percent of African American respondents were aware of African American and white disparities, versus 55 percent of whites. Yet the survey also revealed low levels of awareness among racial and ethnic minority groups about disparities that disproportionately affect their own communities. For example, only 54 percent of African Americans were aware of disparities in the rate of HIV/AIDS between African Americans and whites, and only 21 percent of Hispanics or Latinos were aware of those disparities between their group and whites. Policy makers must increase the availability and quality of data on racial and ethnic health disparities and create multisectoral partnerships to develop targeted educational campaigns to increase awareness of health disparities. PMID- 21976328 TI - High-quality health care: the essential route to eliminating disparities and achieving health equity. AB - In the past decade and a half, the United States has witnessed major advances in the recognition and reporting of health and health care disparities. Now is the time to move beyond describing these disparities to actually eliminating them. Because of the interlocking nature of disparities in health, disparities in health care, and the role of social determinants, there is a need to focus our efforts on one primary goal: achieving health equity by securing access for the entire population to the highest possible quality of health care. Access to high quality care for populations of color can have the same impact as it has for majority populations: improving population health, improving patients' experiences of care, and reducing health care costs. PMID- 21976329 TI - Higher risk of death in rural blacks and whites than urbanites is related to lower incomes, education, and health coverage. AB - Health outcomes among rural minority populations are seldom examined. Our research studied mortality among urban and rural white, black, and Hispanic adults ages 45-64, comparing outcomes for each group. We found the mortality risk to be higher among both rural white and rural minority populations compared to urban whites; rural blacks were at higher risk of death than urban blacks. When personal characteristics and circumstances of these populations-such as level of education, presence of health insurance, and income above or below the poverty line-were held statistically equal, disparities were reduced or eliminated. Our study suggests that policies directed toward reducing differences related to education, poverty, and health insurance would go a long way toward eliminating the disparities in health status between urban and rural populations. PMID- 21976330 TI - Place, not race: disparities dissipate in southwest Baltimore when blacks and whites live under similar conditions. AB - Much of the current health disparities literature fails to account for the fact that the nation is largely segregated, leaving racial groups exposed to different health risks and with variable access to health services based on where they live. We sought to determine if racial health disparities typically reported in national studies remain the same when black and white Americans live in integrated settings. Focusing on a racially integrated, low-income neighborhood of Southwest Baltimore, Maryland, we found that nationally reported disparities in hypertension, diabetes, obesity among women, and use of health services either vanished or substantially narrowed. The sole exception was smoking: We found that white residents were more likely than black residents to smoke, underscoring the higher rates of ill health in whites in the Baltimore sample than seen in national data. As a result, we concluded that racial differences in social environments explain a meaningful portion of disparities typically found in national data. We further concluded that when social factors are equalized, racial disparities are minimized. Policies aimed solely at health behavior change, biological differences among racial groups, or increased access to health care are limited in their ability to close racial disparities in health. Such policies must address the differing resources of neighborhoods and must aim to improve the underlying conditions of health for all. PMID- 21976331 TI - Raising low 'patient activation' rates among Hispanic immigrants may equal expanded coverage in reducing access disparities. AB - There is a growing consensus that activating consumers to become better managers of their health is an essential component of US health care reform. We measured how activated blacks, whites, and Hispanics are-that is, how confident, skillful, and knowledgeable they are about taking an active role in improving their health and health care. We found that patient activation among blacks and Hispanics was low, relative to that of whites. For example, 24.8 percent of Hispanics were at the highest level of patient activation, compared to 39.5 percent of blacks and 45.3 percent of whites. Among Hispanic immigrants, low acculturation and lack of familiarity with the US health care system contribute to low activation. The findings indicate that increasing activation levels among Hispanic immigrants may be as important as expanding insurance coverage in reducing disparities in unmet medical need. PMID- 21976333 TI - Chicago team explores links of environment and biology. AB - Scientists across disciplines collaborate to discover why mortality from breast cancer is higher among African Americans. PMID- 21976332 TI - How cumulative risks warrant a shift in our approach to racial health disparities: the case of lead, stress, and hypertension. AB - Blacks have persistently higher rates of high blood pressure, or hypertension, compared to whites, resulting in higher health costs and mortality rates. Recent research has shown that social and environmental factors-such as high levels of stress and exposure to lead-may explain racial disparities in hypertension. Based on these findings, we recommend a fundamental shift in approaches to health disparities to focus on these sorts of cumulative risks and health effects. Federal and state agencies and research institutions should develop strategic plans to learn more about these connections and apply the broader findings to policies to reduce health disparities. PMID- 21976334 TI - Low-quality, high-cost hospitals, mainly in South, care for sharply higher shares of elderly black, Hispanic, and medicaid patients. AB - As policy makers design national programs aimed at managing the quality and costs of health care, it is important to understand the potential impact on minority and poor patients and the hospitals that provide most of their care. We analyzed a range of hospital data and assigned hospitals to various categories, including "best"-high-quality, low-cost institutions-and "worst"-where quality is low and costs high. We found that the "worst" hospitals-typically small public or for profit institutions in the South-care for double the proportion (15 percent versus 7 percent) of elderly black patients as the "best" hospitals-typically nonprofit institutions in the Northeast. Similarly, elderly Hispanic and Medicaid patients accounted for 1 percent and 15 percent, respectively, of the patient population at the best hospitals, while at the worst hospitals, these groups represented 4 percent and 23 percent of the patients. Patients with acute myocardial infarction at the worst hospitals had 7-10 percent higher odds of death compared to patients with those conditions admitted to the best hospitals. Our findings have important implications for Medicare's forthcoming value-based purchasing program. The worst institutions in particular will have to improve on both costs and quality to avoid incurring financial penalties and exacerbating disparities in care. PMID- 21976335 TI - Rising closures of hospital trauma centers disproportionately burden vulnerable populations. AB - Closures of hospital trauma centers have accelerated since 2001. These closures may disproportionately affect disadvantaged communities. We evaluate how driving time between ZIP code areas and the nearest trauma centers-a proxy for access, given the time-sensitive nature of trauma care-changed nationwide during 2001-07. By 2007, sixty-nine million Americans (24 percent of the population) had to travel farther to the nearest trauma center than they did in 2001, and almost sixteen million people had to travel an additional thirty minutes or more. Communities with disproportionately high numbers of African American residents, uninsured people, and people living in poverty, as well as people living in rural areas, were more likely than others to be thus affected. Because mortality from traumatic injuries has also worsened for these vulnerable populations, policy makers should learn more about the possible connections-and consider such measures as paying trauma centers serving these communities higher amounts for treatment of injuries. PMID- 21976336 TI - Physicians cite hurdles ranging from lack of coverage to poor communication in providing high-quality care to latinos. AB - We surveyed physicians about their ability to provide high-quality care to patients from diverse ethnic backgrounds. Primarily, we wanted to explore the challenges faced by physicians treating Latino patients compared to physicians whose patients were primarily white and non-Latino. We found that physicians treating Latinos, particularly those who worked in primary care in comparison to specialists, were less likely than physicians treating primarily white patients to believe in their ability to provide high-quality care. They cited problems of inadequate time with patients, patients' ability to pay, patients' nonadherence to recommended treatment, difficulties communicating with patients, relative lack of specialist availability, and lack of timely transmission of reports among physicians. Insurance expansions and complementary reforms mandated by the Affordable Care Act of 2010 and other recent legislation should aid physicians in closing some of these gaps in quality. PMID- 21976337 TI - Shared networks of interpreter services, at relatively low cost, can help providers serve patients with limited english skills. AB - Language barriers in health care-a large and growing problem in the United States contribute to disparities in health care quality and outcomes in populations with limited English proficiency. Providing access to adequate interpreter services has been shown to reduce health disparities in these populations. However, many health care organizations do not provide such services because of the perceived high cost. In this observational study we calculated the costs incurred by a group of California public hospitals that formed a network to make trained interpreters available via videoconference and telephone. We found that encounters in this network where interpreters helped patients and providers communicate lasted an average of 10.6 minutes and cost an average of $24.86 per encounter. Such costs should be weighed against the likely alternatives, such as the opportunity costs of having other hospital staff act as ad hoc interpreters; medical errors that could result from inadequate interpretation; and the fact that not providing such services may leave providers out of compliance with federal law. We also discuss ways in which providers could be compensated for providing interpreter services. PMID- 21976338 TI - Despite small improvement, black nursing home residents remain less likely than whites to receive flu vaccine. AB - Vaccination is a key deterrent to influenza and its related complications and outcomes, including hospitalization and death. Using 2006-09 data, we found a small improvement in vaccination rates among nursing home residents, particularly for blacks. Nonetheless, overall vaccination rates remained well below the 90 percent target for high-quality care, and black nursing home residents remained less likely to be vaccinated than whites. Blacks were less likely to be vaccinated than were whites in the same facility and were more likely to live in facilities with lower vaccination rates. Blacks were also more likely to be noted as refusing vaccination. Strategies are needed to ensure that facilities offer vaccination to all residents and to make vaccination more acceptable to black residents and their families. PMID- 21976339 TI - Eliminating health and health care disparities among the growing population of people with disabilities. AB - Fifty-four million people in the United States are now living with disabilities. That number will grow substantially in the next thirty years, as the "baby-boom" generation ages and many of today's children and young adults mature and experience complications related to overweight and obesity. This reality poses a major challenge to the health care and policy communities. People with disabilities confront disadvantages from social and environmental determinants of health, including lower educational levels, lower incomes, and higher unemployment, than people without disabilities. Those with disabilities are also much more likely to report being in fair or poor health; to use tobacco; to forgo physical activity; and to be overweight or obese. People with disabilities also experience health care disparities, such as lower rates of screening and more difficulty accessing services, compared to people without disabilities. Eliminating these multifaceted disadvantages among people with disabilities should be a critical national priority. PMID- 21976340 TI - A regional health collaborative formed By NewYork-Presbyterian aims to improve the health of a largely Hispanic community. AB - Communities of poor, low-income immigrants with limited English proficiency and disproportionate health burdens pose unique challenges to health providers and policy makers. NewYork-Presbyterian Hospital developed the Regional Health Collaborative, a population-based health care model to improve the health of the residents of Washington Heights-Inwood. This area is a predominantly Hispanic community in New York City with high rates of asthma, diabetes, heart disease, and depression. NewYork-Presbyterian created an integrated network of patient centered medical homes to form a "medical village" linked to other providers and community-based resources. The initiative set out to document the priority health needs of the community, target high-prevalence conditions, improve cultural competence among providers, and introduce integrated information systems across care sites. The first six months of the program demonstrated a significant 9.2 percent decline in emergency department visits for ambulatory care-sensitive conditions and a 5.8 percent decrease in hospitalizations that was not statistically significant. This initiative offers a model for other urban academic medical centers to better serve populations facing social and cultural barriers to care. PMID- 21976341 TI - Indian health service innovations have helped reduce health disparities affecting american Indian and alaska native people. AB - The Indian Health Service (IHS), a federal health system, cares for 2 million of the country's 5.2 million American Indian and Alaska Native people. This system has increasingly focused on innovative uses of health information technology and telemedicine, as well as comprehensive, locally tailored prevention and disease management programs, to promote health equity in a population facing multiple health disparities. Important recent achievements include a reduction in the life expectancy gap between American Indian and Alaska Native people and whites (from eight years to five years) and improved measures of diabetes control (including 20 percent and 10 percent reductions in the levels of low-density lipoprotein cholesterol and hemoglobin A1c, respectively). However, disparities persist between American Indian and Alaska Native people and the overall US population. Continued innovation and increased funding are required to further improve health and achieve equity. PMID- 21976343 TI - Collection of race and ethnicity data by health plans has grown substantially, but opportunities remain to expand efforts. AB - In 2003 the Institute of Medicine called on health plans to collect data on their members' race and ethnicity as a foundation for improving the quality of care and reducing disparities. We describe the progress made toward collecting these data, the most commonly used data collection methods, and the challenges plans have encountered. We found that from 2003 through 2008, the proportion of plans that collected members' data on race and ethnicity doubled in the commercial market to 60 percent. It increased even more sharply to 94 percent and 83 percent, respectively, for plans covering Medicaid and Medicare Advantage enrollees. However, the scope of data collection varied greatly across plans, and data collection was an organizationwide initiative in a minority of plans. To fulfill the goals of recent legislation, including the Affordable Care Act, health plans will need to expand their efforts. Among other steps, plans and other key stakeholders should agree on uniform race and ethnicity categories, modify information systems to capture these data, and increase members' trust so that self-reported data-the most accurate data on race and ethnicity-can be gathered. PMID- 21976342 TI - A comprehensive screening and treatment model for reducing disparities in hepatitis B. AB - Chronic hepatitis B affects Asian Americans at a much higher rate than the general US population. Appropriate care can limit morbidity and mortality from hepatitis B. However, access to care for many Asian Americans and other immigrant groups is limited by their lack of knowledge about the disease, as well as cultural, linguistic, and financial challenges. This article describes the results of BfreeNYC, a New York City pilot program that, from 2004 to 2008, provided hepatitis B community education and awareness, free screening and vaccinations, and free or low-cost treatment primarily to immigrants from Asia, but also to residents from other racial and ethnic minority groups. The program was the largest citywide screening program in the United States, reaching nearly 9,000 people, and the only one providing comprehensive care to those who were infected. During the program, new hepatitis B cases reported annually from predominantly Asian neighborhoods in the city increased 34 percent. More than two thousand people were vaccinated, and 1,162 of the 1,632 people who tested positive for hepatitis B received care from the program's clinical services. Our analysis found that the program was effective in reaching the target population and providing care. Although follow-up care data will be needed to demonstrate long-term cost-effectiveness, the program may serve as a useful prototype for addressing hepatitis B disparities in communities across the United States. PMID- 21976344 TI - The corporate role in reducing disparities: initiatives under way at Verizon. AB - Major US employers have great influence on the health care system because of the large number of employees for whom they provide health benefits and the billions of dollars they spend on health care. These companies must find ways to promote and improve health and health care, including by addressing racial and ethnic disparities. The communications company Verizon 38 percent of whose workforce is made up of racial and ethnic minorities, does so through a variety of initiatives to educate employees and to partner with health plans to increase screenings, care management, and other interventions. These initiatives include on-site mammography screening for employees; mailings that describe heightened breast cancer risks for minority populations; and data analysis to determine whether special programs should be put in place to target cardiovascular and other disease risks for racial and ethnic minorities. Between 200 and 300 female employees each year for the past three years have been screened at Verizon for breast cancer as a result, and the company is carrying out additional analyses to determine the impact on morbidity, mortality, and spending for that and other programs. PMID- 21976345 TI - Undocumented immigrants, left out of health reform, likely to continue to grow as share of the uninsured. AB - The increase in undocumented immigration between 1999 and 2007 contributed to an increase in the number of uninsured people in the United States. During this period, the number of undocumented immigrants increased from an estimated 8.5 million to 11.8 million, leading to an estimated additional 1.8 million uninsured. These uninsured and undocumented immigrants were estimated to represent 27 percent of the overall increase of 6.9 million uninsured people during this period. Undocumented immigrants accounted for one in seven of the uninsured in 2007, up from one in eight in 1999. These undocumented immigrants will not be eligible for public insurance or any type of private coverage obtained through exchanges under the Affordable Care Act of 2010. As a result, members of this group will eventually constitute a larger percentage of the uninsured population, unless other policy actions are taken to provide for their coverage, or their immigration status is changed. PMID- 21976346 TI - A dental hygienist who's A Lakota Sioux calls for new mid-level dental providers. AB - High rates of tooth decay and gum disease plague her native Pine Ridge Indian Reservation, along with the rest of Indian Country. PMID- 21976347 TI - Philanthropy and disparities: progress, challenges, and unfinished business. AB - Philanthropy has invested millions of dollars to reduce disparities in health care and improve minority health. Grants to strengthen providers' cultural competence, diversify health professions, and collect data have improved understanding of and spurred action on disparities. The persistence of disparities in spite of these advances has shifted philanthropic attention toward strategies to change social, economic, and environmental conditions. We argue that these evolving perspectives, along with earlier groundwork, present new opportunities for funders, especially in combination with progress toward universal health coverage. This article looks at how philanthropy has addressed health disparities over the past decade, with a focus on accomplishments, the work remaining to be done, and how funders can help advance the disparities agenda. PMID- 21976349 TI - Exaggerating the benefits of the 'decade of vaccines'. PMID- 21976350 TI - Brand-name versus generic drugs. PMID- 21976352 TI - The importance of public health spending. PMID- 21976354 TI - Evaluations of new drugs after they reach the market. PMID- 21976355 TI - Micro-anatomy of the renal sympathetic nervous system: a human postmortem histologic study. AB - Hypertension remains an epidemic uncontrolled with pharmacologic therapies. A novel catheter inserted into the renal artery has been shown to lower blood pressure by ablating the renal sympathetic nerves with radiofrequency energy delivered through the arterial wall. We report a histologic study describing the anatomic substrate for this technique, specifically the renal sympathetic nervous system. Histological sections from proximal, middle, and distal renal artery segments from nine renal arteries (five human autopsies) were analyzed. Nerves were manually counted and their distance from the lumen-intima interface was measured using a micrometer. The nerves were then categorized by location into 0.5-mm-wide "rings" that were arranged circumferentially around the renal artery lumen. Of all nerves detected, 1.0% was in the 0-0.5 mm ring, 48.3% were in the 0.5-1.0 mm ring, 25.6% were in the 1.0-1.5 mm ring, 15.5% were in the 1.5-2.0 mm ring, and 9.5% were in the 2.0-2.5 mm ring. Beyond 0.5 mm, the proportion of nerves tended to decrease as the distance from the lumen increased. Totally, 90.5% of all nerves in this study existed within 2.0 mm of the renal artery lumen. Additionally, the number of nerves tended to increase along the length of the artery from proximal to distal segments (proximal = 216; middle = 323; distal = 417). In conclusion, our analysis indicates that a great proportion of renal sympathetic nerves have close proximity to the lumen-intima interface and should thus be accessible via renal artery interventional approaches such as catheter ablation. This data provides important anatomic information for the development of ablation and other type devices for renal sympathetic denervation. PMID- 21976356 TI - Rostral prefrontal cortex and the focus of attention in prospective memory. AB - Prospective memory (PM) denotes the function to realize intentions after a delay while being immersed in distracting ongoing (OG) activity. Here, we scrutinize the often-reported involvement of rostral prefrontal cortex (rPFC; approximating Brodmann area 10) in such situations: This region might mediate attention between external stimuli and the internally maintained intention, that is, between stimulus-oriented (SO) and stimulus-independent (SI) processing. Using functional magnetic resonance imaging (fMRI) we orthogonally crossed 1) PM versus OG activity only, with 2) SO versus SI attention. In support of the hypothesis, common regions of medial rPFC exhibited greater blood oxygen level-dependent (BOLD) signal for the contrasts of both OG task only versus PM and SO versus SI attending. However, activation related to the former contrast extended more superiorly, suggesting a functional gradient along a dorsal-ventral axis within this region. Moreover, region-of-interest analyses revealed that PM versus OG task only was associated with greater BOLD signal in left lateral rPFC, reflecting the requirement to maintain delayed intentions. Distinct aspects of this region were also transiently engaged at transitions between SO and SI conditions. These results are consistent with the hypothesis that some of the rostral prefrontal signal changes associated with PM performance reflect relative differences in SO versus SI processing. PMID- 21976357 TI - Mannose-functionalized mesoporous silica nanoparticles for efficient two-photon photodynamic therapy of solid tumors. PMID- 21976358 TI - Sensitivity analysis for interactions under unmeasured confounding. AB - We develop a sensitivity analysis technique to assess the sensitivity of interaction analyses to unmeasured confounding. We give bias formulas for sensitivity analysis for interaction under unmeasured confounding on both additive and multiplicative scales. We provide simplified formulas in the case in which either one of the two factors does not interact with the unmeasured confounder in its effects on the outcome. An interesting consequence of the results is that if the two exposures of interest are independent (e.g., gene environment independence), even under unmeasured confounding, if the estimate of the interaction is nonzero, then either there is a true interaction between the two factors or there is an interaction between one of the factors and the unmeasured confounder; an interaction must be present in either scenario. We apply the results to two examples drawn from the literature. PMID- 21976360 TI - Disturbance of reactive oxygen species homeostasis induces atypical tubulin polymer formation and affects mitosis in root-tip cells of Triticum turgidum and Arabidopsis thaliana. AB - In this study, the effects of disturbance of the reactive oxygen species (ROS) homeostasis on the organization of tubulin cytoskeleton in interphase and mitotic root-tip cells of Triticum turgidum and Arabidopsis thaliana were investigated. Reduced ROS levels were obtained by treatment with diphenylene iodonium (DPI) and N-acetyl-cysteine, whereas menadione was applied to achieve ROS overproduction. Both increased and low ROS levels induced: (a) Macrotubule formation in cells with low ROS levels and tubulin paracrystals under oxidative stress. The protein MAP65-1 was detected in treated cells, exhibiting a conformation comparable to that of the atypical tubulin polymers. (b) Disappearance of microtubules (MTs). (c) Inhibition of preprophase band formation. (d) Delay of the nuclear envelope breakdown at prometaphase. (e) Prevention of perinuclear tubulin polymer assembly in prophase cells. (f) Loss of bipolarity of prophase, metaphase and anaphase spindles. Interestingly, examination of the A. thaliana rhd2/At respiratory burst oxidase homolog C (rbohc) NADPH oxidase mutant, lacking RHD2/AtRBOHC, gave comparable results. Similarly to DPI, the decreased ROS levels in rhd2 root-tip cells, interfered with MT organization and induced macrotubule assembly. These data indicate, for first time in plants, that ROS are definitely implicated in: (a) mechanisms controlling the assembly/disassembly of interphase, preprophase and mitotic MT systems and (b) mitotic spindle function. The probable mechanisms, by which ROS affect these processes, are discussed. PMID- 21976359 TI - Cyr61 expression in osteosarcoma indicates poor prognosis and promotes intratibial growth and lung metastasis in mice. AB - Osteosarcoma is the most frequent primary malignant bone tumor in children and adolescents with a high propensity for lung metastasis, the major cause of disease-related death. Reliable outcome-predictive markers and targets for osteosarcoma metastasis-suppressing drugs are urgently needed for more effective treatment of metastasizing osteosarcoma, which has a current mean 5-year survival rate of approximately 20%. This study investigated the prognostic value and the biological relevance of the extracellular matrix-associated growth factor Cyr61 of the CCN family of secreted proteins in osteosarcoma and metastasis. The prognostic value of Cyr61 was assessed with Kaplan-Meier analyses based on Cyr61 immunostaining of a tissue microarray of osteosarcoma biopsies collected from 60 patients with local or metastatic disease. Effects of Cyr61 overexpression on intratibial tumor growth and lung metastasis of the low metastatic human SaOS-2 osteosarcoma cell line were examined in severe combined immunodeficiency (SCID) mice. Cyr61-provoked signaling was studied in vitro in nonmanipulated SaOS-2 cells. Cyr61 immunostaining of osteosarcoma tissue cores correlated significantly (p = 0.02) with poor patient survival. Mice intratibially injected with Cyr61 overexpressing SaOS-2 cells showed faster tumor growth and an increase in number and outgrowth of lung metastases and consequently significantly (p = 0.0018) shorter survival than mice injected with control SaOS-2 cells. Cyr61-evoked PI 3K/Akt/GSK3beta signaling in SaOS-2 cells resulted in a subcellular redistribution of the cell cycle inhibitor p21(Cip1/WAF1). Cyr61 has considerable potential as a novel marker for poor prognosis in osteosarcoma and is an attractive target for primary tumor- and metastases-suppressing drugs. PMID- 21976361 TI - Auditory hallucinations: a comparison of beliefs about voices in individuals with schizophrenia and borderline personality disorder. AB - OBJECTIVE: Individuals with borderline personality disorder (BPD) may experience distressing auditory hallucinations, phenomenologically similar to those seen in psychosis. However, access to effective intervention is limited. The cognitive model of auditory hallucinations highlights the role of appraisals in maintaining distress. Cognitive behavioural therapy (CBT) that targets such beliefs has shown efficacy in psychosis. This study examined appraisals about voices in individuals with psychosis and those with BPD to establish whether CBT for voices might have clinical utility for those with BPD. METHODS: Participants included 45 patients with distressing auditory hallucinations, recruited from the National Health Service. All participants received a structured clinical diagnostic interview and the Beliefs about Voices Questionnaire. Ten participants met criteria for BPD (22%), 23 met criteria for a diagnosis of schizophrenia (51%) and 12 met criteria for both disorders (27%). RESULTS: Multivariate analyses confirmed that there were no group differences in beliefs about the malevolence or omnipotence of voices, or in behavioural resistance or engagement. Those with BPD and those with both diagnoses reported significantly greater emotional resistance than those with schizophrenia. Those with schizophrenia reported significantly greater emotional engagement with their voices. CONCLUSION: Auditory hallucinations in psychosis and BPD do not differ in their phenomenology or cognitive responses (beliefs about the power and malevolence of their dominant voice). The main differential appears to be the affective response. CBT that focuses on appraisals and the relationship with voices may be helpful for distressing auditory hallucinations in individuals with BPD as well as psychosis. PMID- 21976363 TI - Supramolecular zinc phthalocyanine-imidazolyl perylenediimide dyad and triad: synthesis, complexation, and photophysical studies. AB - Two new supramolecular architectures based on zinc phthalocyanine (Pc) and imidazolyl-substituted perylenediimide (PDI), ZnPc/DImPDI/ZnPc 1 and ZnPc/ImPDI 2, have been prepared. A strong electron-donor, ZnPc-8, which contained eight tert-octylphenoxy groups was synthesized to ensure high solubility, thereby reducing aggregation in solution and providing sigma-donor features while avoiding regioisomeric mixtures. Also, PDI units were functionalized with tert octylphenoxy groups at the bay positions, which provide solubility to avoid aggregation in solution, together with one and two imidazole moieties in the amide position, PDI-6 and PDI-4, respectively, to be able to strongly coordinate with the ZnPc complex. Supramolecular complexation studies by (1)H NMR spectroscopy and ESI-MS demonstrate a high coordinative binding constant between imidazole-substituted PDI-4 or PDI-6 and ZnPc-8. The same results were confirmed by UV/Vis and fluorescence titration studies. UV/Vis titration studies revealed the formation of a 1:1 complex ZnPc/ImPDI 2 for the systems ZnPc-8 and PDI-6 and a 2:1 complex ZnPc/DImPDI/ZnPc 1 for the interaction of ZnPc-8 and PDI-4. The binding constant in both cases was determined to be on the order of 10(5) M(-1). Femtosecond laser flash photolysis measurements provided a direct proof of the charge-separated state within both supramolecular assemblies by observing the transient absorption band at 820 nm due to the zinc phthalocyanine radical cation. The lifetimes of charge-separated states are (9.8+/-3) ns for triad 1 and (3+/-1) ns for dyad 2. As far as we know, this is the first time that a radical ion pair has been detected in a supramolecular assembled ZnPc-PDI system and has obtained the longest lifetime of a charge-separated state published for ZnPc-PDI assemblies. PMID- 21976364 TI - The vertebral venous plexuses: the internal veins are muscular and external veins have valves. AB - The internal and external vertebral venous plexuses (VVP) extend the length of the vertebral column. Authoritative sources state that these veins are devoid of valves, permitting bidirectional blood flow and facilitating the hematogenous spread of malignant tumors that have venous connections with these plexuses. The aim of this investigation was to identify morphologic features that might influence blood flow in the VVP. The VVP of 12 adult cadavers (seven female, mean age 79.5 years) were examined by macro- and micro-dissection and representative veins removed for histology and immunohistochemistry (smooth muscle antibody staining). A total of 26, mostly bicuspid, valves were identified in 19 of 56 veins (34%) from the external VVP, all orientated to promote blood flow towards the internal VVP. The internal VVP was characterized by four main longitudinal channels with transverse interconnections; the maximum caliber of the longitudinal anterior internal VVP veins was significantly greater than their posterior counterparts (P < 0.001). The luminal architecture of the internal VVP veins was striking, consisting of numerous bridging trabeculae (cords, thin membranes and thick bridges) predominantly within the longitudinal venous channels. Trabeculae were composed of collagen and smooth muscle and also contained numerous small arteries and nerve fibers. A similar internal venous trabecular meshwork is known to exist within the dural venous sinuses of the skull. It may serve to prevent venous overdistension or collapse, to regulate the direction and velocity of venous blood flow, or is possibly involved in thermoregulation or other homeostatic processes. PMID- 21976365 TI - Rhodium-catalyzed reaction of 1-alkenylboronates with aldehydes leading to allylation products. PMID- 21976366 TI - Gaussian-based routines to impute categorical variables in health surveys. AB - The multivariate normal (MVN) distribution is arguably the most popular parametric model used in imputation and is available in most software packages (e.g., SAS PROC MI, R package norm). When it is applied to categorical variables as an approximation, practitioners often either apply simple rounding techniques for ordinal variables or create a distinct 'missing' category and/or disregard the nominal variable from the imputation phase. All of these practices can potentially lead to biased and/or uninterpretable inferences. In this work, we develop a new rounding methodology calibrated to preserve observed distributions to multiply impute missing categorical covariates. The major attractiveness of this method is its flexibility to use any 'working' imputation software, particularly those based on MVN, allowing practitioners to obtain usable imputations with small biases. A simulation study demonstrates the clear advantage of the proposed method in rounding ordinal variables and, in some scenarios, its plausibility in imputing nominal variables. We illustrate our methods on a widely used National Survey of Children with Special Health Care Needs where incomplete values on race posed a valid threat on inferences pertaining to disparities. PMID- 21976367 TI - Effect of denosumab treatment on the risk of fractures in subgroups of women with postmenopausal osteoporosis. AB - Denosumab reduces the risk of new vertebral and nonvertebral fractures. Previous trials suggest that the efficacy of antiresorptives on fractures might differ by patients' characteristics, such as age, bone mineral density (BMD), and fracture history. In the FREEDOM study, 7808 women aged 60 to 90 years with osteoporosis were randomly assigned to receive subcutaneous injections of denosumab (60 mg) or placebo every 6 months for 3 years. New vertebral and nonvertebral fractures were radiologically confirmed. Subgroup analyses described in this article were prospectively planned before study unblinding to evaluate the effect of denosumab on new vertebral and nonvertebral fractures across various subgroups. Compared with placebo, denosumab decreased the risk of new vertebral fractures in the overall study population over 3 years. This effect did not significantly differ for any of the nine subgroups analyzed (p > 0.09 for all potential interactions). Denosumab also reduced all nonvertebral fractures by 20% in the full study cohort over 3 years. This risk reduction was statistically significant in women with a baseline femoral neck BMD T-score <= -2.5 but not in those with a T-score > -2.5; in those with a body mass index (BMI) < 25 kg/m(2) but not >= 25 kg/m(2); and in those without but not with a prevalent vertebral fracture. These differential treatment effects were not explained by differences in BMD responses to denosumab. Denosumab 60 mg administered every 6 months for 3 years in women with osteoporosis reduced the risk of new vertebral fractures to a similar degree in all subgroups. The effect of denosumab on nonvertebral fracture risk differed by femoral neck BMD, BMI, and prevalent vertebral fracture at baseline. PMID- 21976368 TI - Optimal synthesis of chromatographic trains for downstream protein processing. AB - Downstream bioprocessing and especially chromatographic steps, commonly used for the purification of multicomponent systems, are significant cost drivers in the production of therapeutic proteins. There has been an increased interest in the development of systematic methods for the design of such processes, and the appropriate selection of a series of chromatographic steps is still a major challenge to be addressed. Several models have been developed previously but have assumed that 100% recovery of the desired product is obtained at each chromatographic step. In this work, a mathematical framework is proposed, based on mixed integer optimisation techniques, that removes this assumption and allows full flexibility on the position of retention time cut-points, between which the desired product fraction is collected. The proposed model is demonstrated on three example protein mixtures, each containing up to 13 contaminants and selecting from a set of up to 21 candidate steps. The proposed model results in a reduction of one to three chromatographic steps over solutions that no losses are allowed. PMID- 21976370 TI - Photomodulation of the magnetisation of Co nanocrystals decorated with rhodamine B. PMID- 21976369 TI - An algorithm for 353 odor detection thresholds in humans. AB - One hundred and ninety three odor detection thresholds, ODTs, obtained by Nagata using the Japanese triangular bag method can be correlated as log (1/ODT) by a linear equation with R(2) = 0.748 and a standard deviation, SD, of 0.830 log units; the latter may be compared with our estimate of 0.66 log units for the self-consistency of Nagata's data. Aldehydes, acids, unsaturated esters, and mercaptans were included in the equation through indicator variables that took into account the higher potency of these compounds. The ODTs obtained by Cometto Muniz and Cain, by Cometto-Muniz and Abraham, and by Hellman and Small could be put on the same scale as those of Nagata to yield a linear equation for 353 ODTs with R(2) = 0.759 and SD = 0.819 log units. The compound descriptors are available for several thousand compounds, and can be calculated from structure, so that further ODT values on the Nagata scale can be predicted for a host of volatile or semivolatile compounds. PMID- 21976371 TI - Phosphorous dysregulation induced by MEK small molecule inhibitors in the rat involves blockade of FGF-23 signaling in the kidney. AB - MEK, a kinase downstream of Ras and Raf oncogenes, constitutes a high priority target in oncology research. MEK small molecule inhibitors cause soft tissue mineralization in rats secondary to serum inorganic phosphorus (iP) elevation, but the molecular mechanism for this toxicity remains undetermined. We performed investigative studies with structurally distinct MEK inhibitors GEN-A and PD325901 (PD-901) in Sprague-Dawley rats. Our data support a mechanism that involves FGF-23 signal blockade in the rat kidney, causing transcriptional upregulation of 25-hydroxyvitamin D(3) 1-alpha-hydroxylase (Cyp27b1), the rate limiting enzyme in vitamin D activation, and downregulation of 1,25 dihydroxyvitamin D(3) 24-hydroxylase (Cyp24a1), the enzyme that initiates the degradation of the active form of vitamin D. These transcriptional changes increase serum vitamin D levels, which in turn drive the increase in serum iP, leading to soft tissue mineralization in the rat. PMID- 21976372 TI - The chemokine CCL2 protects against methylmercury neurotoxicity. AB - Industrial pollution due to heavy metals such as mercury is a major concern for the environment and public health. Mercury, in particular methylmercury (MeHg), primarily affects brain development and neuronal activity, resulting in neurotoxic effects. Because chemokines can modulate brain functions and are involved in neuroinflammatory and neurodegenerative diseases, we tested the possibility that the neurotoxic effect of MeHg may interfere with the chemokine CCL2. We have used an original protocol in young mice using a MeHg-contaminated fish-based diet for 3 months relevant to human MeHg contamination. We observed that MeHg induced in the mice cortex a decrease in CCL2 concentrations, neuronal cell death, and microglial activation. Knock-out (KO) CCL2 mice fed with a vegetal control food already presented a decrease in cortical neuronal cell density in comparison with wild-type animals under similar diet conditions, suggesting that the presence of CCL2 is required for normal neuronal survival. Moreover, KO CCL2 mice showed a pronounced neuronal cell death in response to MeHg. Using in vitro experiments on pure rat cortical neurons in culture, we observed by blockade of the CCL2/CCR2 neurotransmission an increased neuronal cell death in response to MeHg neurotoxicity. Furthermore, we showed that sod genes are upregulated in brain of wild-type mice fed with MeHg in contrast to KO CCL2 mice and that CCL2 can blunt in vitro the decrease in glutathione levels induced by MeHg. These original findings demonstrate that CCL2 may act as a neuroprotective alarm system in brain deficits due to MeHg intoxication. PMID- 21976373 TI - Abnormal asymmetry of white matter integrity in schizophrenia revealed by voxelwise diffusion tensor imaging. AB - A number of magnetic resonance imaging (MRI) studies have revealed morphological cortical asymmetry in the normal human brain, and reduction or inversion of such hemispheric asymmetry has been reported in schizophrenia. On the other hand, diffusion tensor imaging (DTI) studies have reported inconsistent findings concerning abnormal asymmetry of white matter integrity in schizophrenia. Our aim was to confirm whether there is reduced or inverted asymmetry of white matter integrity in the whole brain in schizophrenia. For this study, 26 right-handed schizophrenia patients, and 32 matched healthy control subjects were investigated. Voxelwise analysis of DTI data was performed using the tract-based spatial statistics. The fractional anisotropy (FA) images were normalized and projected onto the symmetrical white matter skeleton, and the laterality index (LI) of FA, determined by 2 * (left - right)/(left + right), was calculated. The results reveal that schizophrenia patients and healthy controls showed similar patterns of overall FA asymmetries. In the group comparison, patients showed significant reduction of LI in the external capsule (EC), and posterior limb of the internal capsule (PLIC). The EC cluster revealed increased rightward asymmetry, and the PLIC cluster showed reduced leftward asymmetry. Rightward shift of FA in the EC cluster correlated with negative symptom severity. Considering that the EC cluster includes the uncinate and inferior occipitofrontal fasciculi, which have connections to the orbitofrontal cortex, abnormal asymmetry of white matter integrity in schizophrenia may play a crucial role in the pathogenesis of schizophrenia, through the altered connectivity to the orbitofrontal cortex. PMID- 21976374 TI - Other thoughts on human variation. PMID- 21976376 TI - Palladium-catalyzed decarboxylative intramolecular aziridination from 4H-isoxazol 5-ones leading to 1-azabicyclo[3.1.0]hex-2-enes. PMID- 21976377 TI - Accuracy and cost comparison in medical testing using sequential testing strategies. AB - The practice of sequential testing is followed by the evaluation of accuracy, but not by the evaluation of cost. This paper focuses on three logic rules for combining two sequences of tests: believe the positive (BP), which diagnoses disease if any of two tests is positive, believe the negative (BN), which diagnoses disease if any of two tests is negative, and believe the extreme (BE), which diagnoses disease if the first test is positive or, after a first inconclusive test, a second test is positive for disease. Comparisons of these strategies are provided in terms of accuracy using false positive rate, sensitivity pairs that make up the maximum receiver operating characteristic curve, and cost of testing, defined as the proportion of subjects needing two tests to diagnose disease. A method to incorporate the cost of testing into the definition of the optimal operating point is also presented. The performance of the testing strategies is examined with respect to the ratio of standard deviations and the correlation between test results under the bivariate normal assumptions. Under all parameter settings, the maximum receiver operating characteristic curve of the BE strategy never performed worse than the BN and BP strategies; the BE strategy also had the lowest cost. The use of body mass index and plasma glucose concentration to diagnose diabetes in Pima Indians was presented as a real-world application. The optimal operating points found by the BN and BE strategies produce lower false positive rate values than the BP strategy for these data. PMID- 21976375 TI - PROTS: a fragment based protein thermo-stability potential. AB - Designing proteins with enhanced thermo-stability has been a main focus of protein engineering because of its theoretical and practical significance. Despite extensive studies in the past years, a general strategy for stabilizing proteins still remains elusive. Thus effective and robust computational algorithms for designing thermo-stable proteins are in critical demand. Here we report PROTS, a sequential and structural four-residue fragment based protein thermo-stability potential. PROTS is derived from a nonredundant representative collection of thousands of thermophilic and mesophilic protein structures and a large set of point mutations with experimentally determined changes of melting temperatures. To the best of our knowledge, PROTS is the first protein stability predictor based on integrated analysis and mining of these two types of data. Besides conventional cross validation and blind testing, we introduce hypothetical reverse mutations as a means of testing the robustness of protein thermo-stability predictors. In all tests, PROTS demonstrates the ability to reliably predict mutation induced thermo-stability changes as well as classify thermophilic and mesophilic proteins. In addition, this white-box predictor allows easy interpretation of the factors that influence mutation induced protein stability changes at the residue level. PMID- 21976378 TI - Sequence-based enzyme catalytic domain prediction using clustering and aggregated mutual information content. AB - Characterizing enzyme sequences and identifying their active sites is a very important task. The current experimental methods are too expensive and labor intensive to handle the rapidly accumulating protein sequences and structure data. Thus accurate, high-throughput in silico methods for identifying catalytic residues and enzyme function prediction are much needed. In this paper, we propose a novel sequence-based catalytic domain prediction method using a sequence clustering and an information-theoretic approaches. The first step is to perform the sequence clustering analysis of enzyme sequences from the same functional category (those with the same EC label). The clustering analysis is used to handle the problem of widely varying sequence similarity levels in enzyme sequences. The clustering analysis constructs a sequence graph where nodes are enzyme sequences and edges are a pair of sequences with a certain degree of sequence similarity, and uses graph properties, such as biconnected components and articulation points, to generate sequence segments common to the enzyme sequences. Then amino acid subsequences in the common shared regions are aligned and then an information theoretic approach called aggregated column related scoring scheme is performed to highlight potential active sites in enzyme sequences. The aggregated information content scoring scheme is shown to be effective to highlight residues of active sites effectively. The proposed method of combining the clustering and the aggregated information content scoring methods was successful in highlighting known catalytic sites in enzymes of Escherichia coli K12 in terms of the Catalytic Site Atlas database. Our method is shown to be not only accurate in predicting potential active sites in the enzyme sequences but also computationally efficient since the clustering approach utilizes two graph properties that can be computed in linear to the number of edges in the sequence graph and computation of mutual information does not require much time. We believe that the proposed method can be useful for identifying active sites of enzyme sequences from many genome projects. PMID- 21976379 TI - Quantitative modeling of the Saccharomyces cerevisiae FLR1 regulatory network using an S-system formalism. AB - In this study we address the problem of finding a quantitative mathematical model for the genetic network regulating the stress response of the yeast Saccharomyces cerevisiae to the agricultural fungicide mancozeb. An S-system formalism was used to model the interactions of a five-gene network encoding four transcription factors (Yap1, Yrr1, Rpn4 and Pdr3) regulating the transcriptional activation of the FLR1 gene. Parameter estimation was accomplished by decoupling the resulting system of nonlinear ordinary differential equations into a larger nonlinear algebraic system, and using the Levenberg-Marquardt algorithm to fit the models predictions to experimental data. The introduction of constraints in the model, related to the putative topology of the network, was explored. The results show that forcing the network connectivity to adhere to this topology did not lead to better results than the ones obtained using an unrestricted network topology. Overall, the modeling approach obtained partial success when trained on the nonmutant datasets, although further work is required if one wishes to obtain more accurate prediction of the time courses. PMID- 21976381 TI - A systems biology approach for detecting toxicity-related hotspots inside protein interaction networks. AB - Drug-induced neutropenia can be fatal when severe and therefore requires an improved understanding of its mechanism(s) of toxicity. Systems biology provides an opportunity to understand adverse events after drug administration using analysis of biomolecular networks. In this study, a human protein interaction network was analyzed to identify proteins that are most central to topological paths connecting a drug's target proteins to hematopoiesis-related proteins. For a set of non-immune neutropenia inducing drugs, 9 proteins were found to be common to putative signaling paths across all drugs evaluated. All 9 proteins showed relevance to neutrophil biology. Geneset enrichment analysis showed that proteins associated with cancer-related processes such as apoptosis provide topological linkages between drug targets and proteins involved in neutrophil production. The algorithm can be applied towards analysis of any toxicity where the drugs and the physiological processes involved in the toxic mechanism are known. PMID- 21976380 TI - A compressed sensing based approach for subtyping of leukemia from gene expression data. AB - With the development of genomic techniques, the demand for new methods that can handle high-throughput genome-wide data effectively is becoming stronger than ever before. Compressed sensing (CS) is an emerging approach in statistics and signal processing. With the CS theory, a signal can be uniquely reconstructed or approximated from its sparse representations, which can therefore better distinguish different types of signals. However, the application of CS approach to genome-wide data analysis has been rarely investigated. We propose a novel CS based approach for genomic data classification and test its performance in the subtyping of leukemia through gene expression analysis. The detection of subtypes of cancers such as leukemia according to different genetic markups is significant, which holds promise for the individualization of therapies and improvement of treatments. In our work, four statistical features were employed to select significant genes for the classification. With our selected genes out of 7,129 ones, the proposed CS method achieved a classification accuracy of 97.4% when evaluated with the cross validation and 94.3% when evaluated with another independent data set. The robustness of the method to noise was also tested, giving good performance. Therefore, this work demonstrates that the CS method can effectively detect subtypes of leukemia, implying improved accuracy of diagnosis of leukemia. PMID- 21976382 TI - Improved refractive-index sensitivity of silver-nanocube monolayers on silicon films. PMID- 21976383 TI - Desorption dynamics, internal energies, and imaging of organic molecules from surfaces with laser desorption and vacuum ultraviolet (VUV) photoionization. AB - There is enormous interest in visualizing the chemical composition of organic material that comprises our world. A convenient method to obtain molecular information with high spatial resolution is imaging mass spectrometry. However, the internal energy deposited within molecules upon transfer to the gas phase from a surface can lead to increased fragmentation and to complications in analysis of mass spectra. Here it is shown that in laser desorption with postionization by tunable vacuum ultraviolet (VUV) radiation, the internal energy gained during laser desorption leads to minimal fragmentation of DNA bases. The internal temperature of laser-desorbed triacontane molecules approaches 670 K, whereas the internal temperature of thymine is 800 K. A synchrotron-based VUV postionization technique for determining translational temperatures reveals that biomolecules have translational temperatures in the range of 216-346 K. The observed low translational temperatures as well as their decrease with increased desorption laser power is explained by collisional cooling. An example of imaging mass spectrometry on an organic polymer by using laser-desorption VUV postionization shows 5 MUm feature details while using a 30 MUm laser spot size and 7 ns pulse duration. Applications of laser-desorption postionization to the analysis of cellulose, lignin, and humic acids are briefly discussed. PMID- 21976384 TI - Flexibility in embodied lexical-semantic representations. AB - According to an embodied view of language comprehension, language concepts are grounded in our perceptual systems. Evidence for the idea that concepts are grounded in areas involved in action and perception comes from both behavioral and neuroimaging studies (Glenberg [1997]: Behav Brain Sci 20:1-55; Barsalou [1999]: Behav Brain Sci 22:577-660; Pulvermueller [1999]: Behav Brain Sci 22:253 336; Barsalou et al. [2003]: Trends Cogn Sci 7:84-91). However, the results from several studies indicate that the activation of information in perception and action areas is not a purely automatic process (Raposo et al. [2009]: Neuropsychologia 47:388-396; Rueschemeyer et al. [2007]: J Cogn Neurosci 19:855 865). These findings suggest that embodied representations are flexible. In these studies, flexibility is characterized by the relative presence or absence of activation in our perceptual systems. However, even if the context in which a word is presented does not undermine a motor interpretation, it is possible that the degree to which a modality-specific region contributes to a representation depends on the context in which conceptual features are retrieved. In the present study, we investigated this issue by presenting word stimuli for which both motor and visual properties (e.g., Tennis ball, Boxing glove) were important in constituting the concept. Conform with the idea that language representations are flexible and context dependent, we demonstrate that the degree to which a modality-specific region contributes to a representation considerably changes as a function of context. PMID- 21976385 TI - Unusual presentation of extensor digitorum brevis manus: Two cases report. PMID- 21976386 TI - Carboplatin and pegylated liposomal doxorubicin versus carboplatin and paclitaxel in partially platinum-sensitive ovarian cancer patients: results from a subset analysis of the CALYPSO phase III trial. AB - BACKGROUND: To perform a subset analysis of patients with partially platinum sensitive recurrent ovarian cancer (ROC) who received either CD [carboplatin pegylated liposomal doxorubicin (PLD)] or CP (carboplatin-paclitaxel) in the CALYPSO trial. PATIENTS AND METHODS: CALYPSO, an international phase III, non inferiority trial, enrolled women with ROC that relapsed >6 months following first- or second-line therapy. Patients were randomized to CD or CP. Patients with a treatment-free interval of >6 and <= 12 months were evaluated for progression-free survival (PFS), the primary end point of CALYPSO trial, and safety. RESULTS: A total of 344 partially platinum-sensitive patients were included (N = 161, CD and N = 183, CP). The hazard ratio for PFS was 0.73 (95% confidence interval: 0.58-0.90; P = 0.004 for superiority) in favor of CD. Median PFS times were 9.4 months (CD) and 8.8 months (CP). Toxicities more common with CP versus CD included grade 3/4 neutropenia (50% versus 39%; P = 0.015), grade 2 alopecia (86% versus 9%; P < 0.001), neuropathy and hypersensitivity reactions. Hand-foot syndrome was more common with CD; however, grade 3/4 reactions were low (one patient in each arm). CONCLUSION: Carboplatin-PLD has a more favorable risk benefit profile than CP in patients with partially platinum-sensitive ROC and should be considered an effective treatment option for these patients. PMID- 21976387 TI - Adverse events risk associated with bevacizumab addition to breast cancer chemotherapy: a meta-analysis. AB - BACKGROUND: Bevacizumab is a monoclonal antibody against vascular endothelial growth factor with the ability to increase progression-free survival in metastatic breast cancer (MBC). A systematic review and meta-analysis was conducted to determine the risk of the most clinically relevant adverse outcomes associated with the use of bevacizumab in the treatment of breast cancer. PATIENTS AND METHODS: We included phase III clinical trials that used bevacizumab alone or in combination with chemotherapy as for MBC or locally recurrent. Statistical analyses were conducted to calculate summary odds ratio (OR) of the eight most relevant adverse outcomes related with bevacizumab. RESULTS: Five clinical trials were included in the meta-analysis. Summary odds ratios obtained showed a statistically significant bevacizumab-associated increased risk in four of the adverse outcomes studied: proteinuria (OR = 27.68), hypertension (OR = 12.76), left ventricular dysfunction (LVD) (OR = 2.25), and hemorrhagic events (OR = 4.07). No statistically significant differences were found for gastrointestinal (GI) perforation, vascular events, fatal events, or febrile neutropenia. CONCLUSIONS: Bevacizumab did increase the risk of LVD and hemorrhagic events. The addition of bevacizumab to chemotherapy in patients with metastatic breast cancer was not associated with a significant increase in grade >= 3 arterial or venous thromboembolic events, GI perforation, or fatal events. PMID- 21976388 TI - Potential role of phytoestrogens in the pathophysiology of fibromatosis. PMID- 21976389 TI - Bayesian analysis of the structural equation models with application to a longitudinal myopia trial. AB - Myopia is becoming a significant public health problem, affecting more and more people. Studies indicate that there are two main factors, hereditary and environmental, suspected to have strong impact on myopia. Motivated by the increase in the number of people affected by this problem, this paper focuses primarily on the utilization of mathematical methods to gain further insight into their relationship with myopia. Accordingly, utilizing multidimensional longitudinal myopia data with correlation between both eyes, we develop a Bayesian structural equation model including random effects. With the aid of the MCMC method, it is capable of expressing the correlation between repeated measurements as well as the two-eye correlation and can be used to explore the relational structure among the variables in the model. We consider four observed factors, including intraocular pressure, anterior chamber depth, lens thickness, and axial length. The results indicate that the genetic effect has much greater influence on myopia than the environmental effects. PMID- 21976390 TI - A catalytic asymmetric borono variant of Hosomi-Sakurai reactions with N,O aminals. PMID- 21976393 TI - A piezoresistive tactile sensor for tissue characterization during catheter-based cardiac surgery. AB - BACKGROUND: Currently, most of mitral valve annuloplasty surgeries are performed by using open heart surgery. However, if such operation would be performed by using minimally invasive surgery via catheter-based techniques (CBT), it offers various advantages for both surgeons and patients. METHODS: Two piezoresistive force sensors are used in the structure of the tactile sensor, which can easily be miniaturized and integrated into surgical catheters. The tactile sensor was fabricated and tested to characterize different elastomers, as the phantom of cardiac tissues. Based on a developed finite element analysis (FEA) of the elastomers, the interaction between the sensor and those materials were modelled to validate the output of the sensor. RESULTS: The results of the mechanical and psychophysical tests confirm the capability of the proposed sensor to measure the relative hardness/softness of different soft tissues. CONCLUSIONS: The proposed tactile sensor will help surgeons to characterize different types of cardiac tissues and would facilitate the use of CBT to perform mitral valve annuloplasty. PMID- 21976394 TI - Synthesis and applications of tricarbonyliron complexes of dendralenes. AB - [3]Dendralene and [4]dendralene are converted smoothly into tricarbonyliron complexes. The structures of four complexes analyzed by DFT and single-crystal X ray analysis show that, in contrast to free hydrocarbons, complexed dendralenes prefer a roughly in-plane conformation. The complexes are stable towards Fe(CO)(3) group migration up to 150 degrees C. The synthetic value of Fe(CO)(3) complexation in the dendralene series is demonstrated through a variety of selective synthetic manipulations (Diels-Alder reaction, dipolar cycloaddition, Simmons-Smith cyclopropanation, dihydroxylation, olefin cross metathesis) that are not achievable by direct transformation of the free hydrocarbons. Application to the synthesis of a previously unreported, highly reactive linear/cross conjugated hydrocarbon is also described. PMID- 21976392 TI - Neural processes of preparatory control for stop signal inhibition. AB - This study investigated the preparatory control of motor inhibition and motor execution using a stop signal task (SST) and functional magnetic resonance imaging (fMRI). In the SST, a frequent "go" signal triggered a prepotent response and a less frequent "stop" signal prompted the inhibition of this response. Preparatory control of motor inhibition and execution in the stop signal trials were examined by contrasting brain activation between stop success and stop error trials during the fore-period, in which participants prepared to respond to go or to stop. Results from 91 healthy adults showed greater activation in the right prefrontal cortex and inferior parietal lobule during preparatory motor inhibition. Preparatory motor execution activated bilateral putamen, primary motor cortices, posterior cingulate cortex, ventromedial prefrontal cortex, and superior temporal/intraparietal sulci. Furthermore, the extents of these inhibition and execution activities were inversely correlated across subjects. On the basis of a median split of the stop signal reaction time (SSRT), subjects with short SSRT showed greater activity in the right orbital frontal cortex during preparatory inhibition. These new findings suggest that the go and stop processes interact prior to target presentation in the SST, in accord with recent computational models of stop signal inhibition. PMID- 21976395 TI - Internal supravesical hernia: an unusual cause of small bowel obstruction. AB - Internal hernia of the supravesical fossa is an unusual cause of small bowel obstruction. We report the case of a patient without previous abdominal surgery with an acute abdominal obstruction in which laparoscopic exploration revealed a strangulated internal supravesical hernia. To help clinicians with their pre operative diagnosis and to better understand the clinical management of this unusual internal hernia, a description of the anatomy of the supravesical fossa is included in this case report. PMID- 21976396 TI - Neonatal intensive care unit stress is associated with brain development in preterm infants. AB - OBJECTIVE: Although many perinatal factors have been linked to adverse neurodevelopmental outcomes in very premature infants, much of the variation in outcome remains unexplained. The impact on brain development of 1 potential factor, exposure to stressors in the neonatal intensive care unit, has not yet been studied in a systematic, prospective manner. METHODS: In this prospective cohort study of infants born at <30 weeks gestation, nurses were trained in recording procedures and cares. These recordings were used to derive Neonatal Infant Stressor Scale scores, which were employed to measure exposure to stressors. Magnetic resonance imaging (brain metrics, diffusion, and functional magnetic resonance imaging) and neurobehavioral examinations at term equivalent postmenstrual age were used to assess cerebral structure and function. Simple and partial correlations corrected for confounders, including immaturity and severity of illness, were used to explore these relations. RESULTS: Exposure to stressors was highly variable, both between infants and throughout a single infant's hospital course. Exposure to a greater number of stressors was associated with decreased frontal and parietal brain width, altered diffusion measures and functional connectivity in the temporal lobes, and abnormalities in motor behavior on neurobehavioral examination. INTERPRETATION: Exposure to stressors in the Neonatal Intensive Care Unit is associated with regional alterations in brain structure and function. Further research into interventions that may decrease or mitigate exposure to stressors in the neonatal intensive care unit is warranted. PMID- 21976397 TI - Nanoporous organic alloys. PMID- 21976398 TI - Efficacy and safety of enteric-coated mycophenolate sodium in combination with two glucocorticoid regimens for the treatment of active lupus nephritis. AB - Mycophenolic acid, in combination with glucocorticoids, has been shown in a series of trials to be safe and effective for treatment of lupus nephritis. Regimens that permit glucocorticoid dose reduction without loss of efficacy would be advantageous. MyLupus was a 24-week, multicentre, open-label, study in patients with active proliferative lupus nephritis treated with enteric-coated mycophenolate sodium (EC-MPS), randomized to standard-dose (n = 42) or reduced dose (n = 39) glucocorticoids. Complete response at week 24, the primary endpoint, was achieved in 19.8% (16/81) of patients (19.0% standard-dose, 20.5% reduced-dose; lower limit of 97.5% CI for the difference -15.9%, p = 0.098, i.e. non-inferiority was not shown). Partial response occurred in 42.0% of patients (34/81). From baseline to week 24, the mean global British Isles Lupus Assessment Group (BILAG) score decreased from 14.0 +/- 5.4 to 5.0 +/- 3.8 (p < 0.001). The incidence of adverse events was 80.2% (65/81), most frequently gastrointestinal complications (31/81, 38.3%). Infections were reported in 57.1% and 35.9% of standard- and reduced-dose glucocorticoid patients, respectively (p = 0.056), with herpes zoster in 16.7% and 0% (p = 0.012). Three patients discontinued study medication due to adverse events. This exploratory study suggests that EC-MPS may facilitate glucocorticoid reduction without loss of efficacy in patients with active lupus nephritis, but results require confirmation in a controlled, longer term study versus the current standard of care. PMID- 21976399 TI - Progressive multifocal leukoencephalopathy associated with mycophenolate mofetil treatment in a woman with lupus and CD4+ T-lymphocyte deficiency. AB - There is an increase in the number of patients with systemic lupus erythematosus (SLE) reported as developing progressive multifocal leukoencephalopathy (PML) while on intensive immunosuppressive therapy. A 39-year-old HIV-negative woman with a 10-year history of SLE presented with progressive left-side weakness while on maintenance therapy with oral prednisone and mycophenolate mofetil (MMF). On several occasions low CD4+ T-lymphocyte counts were found (68/uL). Brain magnetic resonance imaging (MRI) revealed a large lesion in the right subcortical fronto parietal region and a smaller one in the left frontal subcortex, corresponding to the PML. In cerebrospinal fluid, polymerase chain reaction (PCR) for JC virus (JCV) was negative, but anti-JCV antibodies were highly positive. Diagnosis of probable PML was made and MMF was withdrawn. The patient's condition improved with marked reduction of left-side weakness and an increase in CD4(+) T lymphocyte count (141/uL). Follow-up MRI showed regression of lesions and over the next 6 months the patient remained stable. In spite of the grave prognosis associated with PML, SLE patients can have an excellent outcome if immunosuppressants are discontinued as soon as the correct diagnosis is made. SLE patients with associated low CD4(+) T-lymphocyte counts should be monitored for the development of PML during immunosuppressive therapy in particular. PMID- 21976400 TI - Aggravated capillary non-perfusion after intravitreal bevacizumab for macular edema secondary to systemic lupus erythematosus and anti-phospholipid syndrome. AB - A 22-year-old female with history of systemic lupus erythematosus (SLE) was referred for evaluation of decreased visual acuity in her right eye. Her best corrected visual acuity (BCVA) at the time of presentation was 20/160. Widespread cotton wool spots and macular edema were seen on biomicroscopy. Fluorescein angiography (FA) revealed retinal arterial and venous obstruction with capillary nonperfusion at the superotemporal retina. Antiphospholipid syndrome (APS) was diagnosed based on positive lupus anti-coagulant and ocular manifestations. Scattered laser photocoagulation was applied at the nonperfusion area but the visual acuity continued to deteriorate due to macular edema. Intravitreal bevacizumab (IVB) was administered for macular edema. One day after IVB, the BCVA decreased to count fingers. FA revealed extended non-perfusion from the superotemporal area to the posterior pole. Use of intravitreal bevacizumab for macular edema secondary to SLE or APS should be considered carefully and patients monitored closely for vascular complications. PMID- 21976401 TI - Kidney transplantation outcomes in African-, Hispanic- and Caucasian-Americans with lupus. AB - African-American recipients of kidney transplants with lupus have high allograft failure risk. We studied their risk adjusting for: (1) socio-demographic factors: donor age, gender and race-ethnicity; recipient age, gender, education and insurance; donor-recipient race-ethnicity match; (2) immunologic factors: donor type, panel reactive antibodies, HLA mismatch, ABO blood type compatibility, pre transplant dialysis, cytomegalovirus risk and delayed graft function (DGF); (3) rejection and recurrent lupus nephritis (RLN). Two thousand four hundred and six African-, 1132 Hispanic-, and 2878 Caucasian-Americans were followed for 12 years after transplantation. African- versus Hispanic- and Caucasian-Americans received more kidneys from deceased donors (71.6%, 57.3% and 55.1%) with higher two HLA loci mismatches for HLA-A (50%, 39.6% and 32.4%), HLA-B (52%, 42.8% and 35.6%) and HLA-DR (30%, 24.5% and 21.1%). They developed more DGF (19.5%, 13.6% and 13.4%). More African- versus Hispanic- and Caucasian-Americans developed rejection (41.7%, 27.6% and 35.9%) and RLN (3.2, 1.8 and 1.8%). 852 African-, 265 Hispanic-, and 747 Caucasian-Americans had allograft failure (p < 0.0001). After adjusting for transplant era, socio-demographic-immunologic differences, rejection and RLN, the increased hazard ratio for allograft failure of African- compared with Caucasian-Americans became non-significant (1.26 [95% confidence interval 0.78-2.04]). African-Americans with lupus have high prevalence of risk factors for allograft failure that can explain poor outcomes. PMID- 21976402 TI - Novel cardiovascular risk prediction models in patients with systemic lupus erythematosus. AB - Women with systemic lupus erythematosus (SLE) have increased risk for coronary heart disease (CHD) which is underestimated by the Framingham risk score (FRS). We hypothesized that new risk scores that include inflammation or vascular age in the risk calculation would better identify women with SLE at risk for CHD, particularly in those with subclinical coronary atherosclerosis. We calculated the FRS and Reynolds risk score (RRS) in 121 women with SLE and 65 age-matched female controls; coronary age-modified risk scores (camFRS, camRRS) were calculated using coronary age derived from the coronary artery calcium (CAC) score. Risk scores were compared in SLE and controls, and in SLE patients with and without CAC. Although CAC was present in 21 SLE patients (17%) and four controls (6%) (p = 0.033); the FRS, camFRS, RRS, and camRRS, did not differ significantly among SLE and controls (p > 0.05), but were all significantly higher in SLE patients with CAC compared with those without (p < 0.001 for all). The camFRS (8%, p = 0.016) but not camRRS (5%, p = 0.221) assigned significantly more SLE patients to a category of >= 10% risk than conventional FRS (1%) and RRS (2%). The RRS was of limited use but coronary age may improve CHD risk prediction in SLE. PMID- 21976403 TI - 1H NMR-based metabolomic study of metabolic profiling for systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is a chronic inflammatory disease characterized by multi-system involvement, diverse clinical presentation, and alterations in circulating metabolites. In this study, a (1)H NMR spectroscopy based metabolomics approach was applied to establish a human SLE serum metabolic profile. Serum samples were obtained from patients with SLE (n = 64), patients with rheumatoid arthritis (RA) (n = 30) and healthy controls (n = 35). The NOESYPR1D spectrum combined with multi-variate pattern recognition analysis was used to cluster the groups and establish a disease-specific metabolites phenotype. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were capable of distinguishing SLE or RA patients from healthy subjects. The OPLS-DA model was able to predict diagnosis of SLE with a sensitivity rate of 60.9% and a specificity rate of 97.1%. For diagnosing RA, the model has much higher sensitivity (96.7%) and specificity (91.4%). The SLE serum samples were characterized by reduced concentrations of valine, tyrosine, phenylalanine, lysine, isoleucine, histidine, glutamine, alanine, citrate, creatinine, creatine, pyruvate, high-density lipoprotein, cholesterol, glycerol, formate and increased concentrations of N acetyl glycoprotein, very low-density lipoprotein and low-density lipoprotein in comparison with the control population. The results not only indicated that serum NMR-based metabolomic methods had sufficient sensitivity and specificity to distinguish SLE and RA from healthy controls, but also have the potential to be developed into a clinically useful diagnostic tool, and could also contribute to a further understanding of disease mechanisms. PMID- 21976404 TI - Angiotensin-converting enzyme (ACE) serum levels and gene polymorphism in Egyptian patients with systemic lupus erythematosus. AB - OBJECTIVES: To investigate the association of angiotensin-converting enzyme (ACE) gene polymorphism and serum ACE level among Egyptian SLE patients and its relation to disease activity parameters. SUBJECTS AND METHODS: We enrolled 50 Egyptian female systemic lupus erythematosus (SLE) patients and 29 healthy controls. Measurement of serum ACE level was done using ELISA, and the ACE genotype was determined by polymerase chain reaction using genomic DNA from peripheral blood. RESULTS: A significant difference was found in ACE genotypes between SLE patients and controls (chi(2 )= 7.84, p = 0.02). The frequency of ACE DD versus (DI and II) genotypes was significantly higher in SLE patients compared with controls (chi(2 )= 5.57, p = 0.018 and OR for risk of SLE was 3.1 with 95% confidence interval: 1.198.06). Mean serum ACE level was significantly higher in the SLE group compared with controls (p = 0.006). Subjects with DD genotype had a significantly higher mean level than those with DI (p = 0.015) and II genotypes (p = 0.02). Lupus nephritis patients had a significantly higher frequency of DD versus DI and II genotypes compared with lupus patients without nephritis (Fisher's exact test, p = 0.025) and controls (chi (2) =8.74, p = 0.003). SLE patients with vasculopathy had a significantly higher frequency of DD versus DI/II genotypes compared with SLE patients without vasculopathy (Fisher's exact test, p = 0.04) and controls (chi(2 )= 9.84 and p = 0.002). Mean serum ACE level was significantly higher in the lupus nephritis and SLE patients with vasculopathy compared with controls (p = 0.008, p = 0.001, respectively). Significant positive correlations were found between serum ACE level and serum creatinine and 24 h proteinuria (p = 0.03, 0.009, respectively). SLE patients with DD genotype had a statistically significant higher mean SLEDAI score than those with (DI/II) genotypes (p = 0.02). Significant positive correlation was found between serum ACE levels and SLEDAI scores (p = 0.04). CONCLUSION: ACE genotype and subsequently serum ACE level could be associated with the disease activity of Egyptian SLE patients; in addition, ACE deletion polymorphism might be used as one of the predictive factors for the activity of SLE. Further studies on a larger number of patients should be done to determine the exact prevalence of ACE gene polymorphism among Egyptian SLE patients. PMID- 21976405 TI - Constitutive abnormal expression of RasGRP-1 isoforms and low expression of PARP 1 in patients with systemic lupus erythematosus. AB - OBJECTIVE: Defective expression of Ras guanil releasing protein-1 (RasGRP-1) and increased apoptosis have been reported in lymphocytes from SLE patients. Whether these aberrations are correlated and linked to disease activity has not been elucidated. METHODS: Expression of normal 90 kDa RasGRP-1, its most prevalent 86 kDa isoform and full PARP-1 116 kDa and its cleavage fragment 84 kDa were determined in whole protein lysates of peripheral blood mononuclear cells (PBMC) in correlation with mitogen activated protein kinase (MAPK) activity and SLE clinical status in a large group of SLE patients during 1 year follow-up. RESULTS: Expression of normal 90 kDa RasGRP-1 was comparable in patients and controls. However, SLE patients demonstrated a constitutively increased 86 kDa/90 kDA ratio (p < 0.01) and decreased full poly (ADP-ribose) polymerase protein-1 (PARP-1) expression (p < 0.002) compared with controls who were disease independent. A remission in disease activity was associated with decreased RasGRP 1 expression. Expression of 84 kDa PARP-1 cleavage fragment was found in 15% of patients but in none of the controls. In addition, expression of PARP-1 correlated positively with normal 90 kDa RasGRP-1 expression and negatively with the RasGRP-1 86 kDa/90 kDA ratio. CONCLUSIONS: These data suggest that constitutive aberrant expression of PARP-1 and RasGRP-1 ratio may act in concert to impair survival of lymphocytes in SLE patients. PMID- 21976406 TI - The effect of hypointense white matter lesions on automated gray matter segmentation in multiple sclerosis. AB - Previous imaging studies assessing the relationship between white matter (WM) damage and matter (GM) atrophy have raised the concern that Multiple Sclerosis (MS) WM lesions may affect measures of GM volume by inducing voxel misclassification during intensity-based tissue segmentation. Here, we quantified this misclassification error in simulated and real MS brains using a lesion filling method. Using this method, we also corrected GM measures in patients before comparing them with controls in order to assess the impact of this lesion induced misclassification error in clinical studies. We found that higher WM lesion volumes artificially reduced total GM volumes. In patients, this effect was about 72% of that predicted by simulation. Misclassified voxels were located at the GM/WM border and could be distant from lesions. Volume of individual deep gray matter (DGM) structures generally decreased with higher lesion volumes, consistent with results from total GM. While preserving differences in GM volumes between patients and controls, lesion-filling correction revealed more lateralised DGM shape changes in patients, which were not evident with the original images. Our results confirm that WM lesions can influence MRI measures of GM volume and shape in MS patients through their effect on intensity-based GM segmentation. The greater effect of lesions at increasing levels of damage supports the use of lesion-filling to correct for this problem and improve the interpretability of the results. Volumetric or morphometric imaging studies, where lesion amount and characteristics may vary between groups of patients or change over time, may especially benefit from this correction. PMID- 21976408 TI - 5-(Pyren-1-yl)uracil as a base-discriminating fluorescent nucleobase in pyrrolidinyl peptide nucleic acids. AB - A pyrene-labeled uridine (U(Py)) monomer for a pyrrolidinyl peptide nucleic acid with an alternating proline/2-aminocyclopentanecarboxylic acid backbone (acpcPNA) was synthesized and incorporated into the PNA. The U(Py) base in acpcPNA could specifically recognize the base A in its complementary DNA strand as determined by thermal denaturation (T(m)) experiments. The fluorescence of the U(Py) containing single-stranded acpcPNA was very weak in aqueous buffer. In the presence of a complementary DNA target, the fluorescence was enhanced significantly (2.7-41.9 folds, depending on sequences). The fluorescence enhancement was specific to the pairing between U(Py) and dA, making the U(Py) modified acpcPNA useful as a hybridization-responsive fluorescence probe for DNA sequence determination. PMID- 21976407 TI - Genetic variability in DNA repair and cell cycle control pathway genes and risk of smoking-related lung cancer. AB - DNA repair and cell cycle control play an important role in the repair of DNA damage caused by cigarette smoking. Given this role, functionally relevant single nucleotide polymorphisms (SNPs) in genes in these pathways may well affect the risk of smoking-related lung cancer. We examined the relationship between 240 SNPs in DNA repair and cell cycle control pathway genes and lung cancer risk in a case-control study of white current and ex-cigarette smokers (722 cases and 929 controls). Additive, dominant, and recessive genetic models were evaluated for each SNP. A genetic risk summary score was also constructed. Odds ratios (OR) for lung cancer risk and 95% confidence intervals (95% CI) were estimated using logistic regression models. Thirty-eight SNPs were associated with lung cancer risk in our study population at P < 0.05. The strongest associations were observed for rs2074508 in GTF2H4 (P(additive) = 0.003), rs10500298 in LIG1 (P(recessive) = 2.7 * 10(-4)), rs747658 and rs3219073 in PARP1 (rs747658: P(additive) = 5.8 * 10(-5); rs3219073: P(additive) = 4.6 * 10(-5)), and rs1799782 and rs3213255 in XRCC1 (rs1799782: P(dominant) = 0.006; rs3213255: P(recessive) = 0.004). Compared to individuals with first quartile (lowest) risk summary scores, individuals with third and fourth quartile summary score results were at increased risk for lung cancer (OR: 2.21, 95% CI: 1.66-2.95 and OR: 3.44, 95% CI: 2.58-4.59, respectively; P(trend) < 0.0001). Our data suggests that variation in DNA repair and cell cycle control pathway genes is associated with smoking-related lung cancer risk. Additionally, combining genotype information for SNPs in these pathways may assist in classifying current and ex-cigarette smokers according to lung cancer risk. PMID- 21976409 TI - Attenuation of low dose methylmercury and glutamate induced-cytotoxicity and tau phosphorylation by an N-methyl-D-aspartate antagonist in human neuroblastoma (SHSY5Y) cells. AB - Methylmercury (MeHg), a known neurotoxin, has been reported to alter glutamate homeostasis in the neuronal environment resulting in excitotoxicity. This study was conducted to investigate whether, and if so, under what conditions, that low dose MeHg would enhance the toxicity of glutamate and to what extent that blockade of NMDA receptors would alter MeHg and glutamate's toxicity in cultured neuroblastoma cells. Neuroblastoma cells (SH-SY5Y) were used in a cell culture model to study effects of MeHg, glutamate (glu), a calcium chelator (BAPTA-AM), and a noncompetitive NMDA antagonist, MK-801 on cell growth, cell survival, and phosphorylation of tau protein, as a measure of cellular events associated with tauopathies. Exposure of cells to a combination of MeHg (50 nM) and glutamate (1 mM) resulted in both a greater decrease in cell viability as well as a greater induction in tau phosphorylation, as compared to exposures with MeHg and glutamate alone. MK-801, an NMDA receptor antagonist, and the intracellular calcium chelator, BAPTA-AM, both significantly inhibited tau hyperphosphorylation and protected cells from the effects of combination exposures to glutamate and MeHg. These results may indicate that exposure to even nontoxic levels of MeHg may prime neuronal cells to be more susceptible to neuronal injury from excitotoxicants such as glutamate and thus may increase the likelihood of neurological disease states. In conclusion, low-dose MeHg-induced toxicity may be related to an increase in the cellular response to glutamate and that NMDA receptor antagonists may provide a potential treatment for MeHg-associated neurological diseases. PMID- 21976410 TI - Ferrocenyl-substituted metallacycles of titanocenes: oligocyclopentadienyl complexes with promising properties. PMID- 21976411 TI - Modeling conflict and error in the medial frontal cortex. AB - Despite intensive study, the role of the dorsal medial frontal cortex (dMFC) in error monitoring and conflict processing remains actively debated. The current experiment manipulated conflict type (stimulus conflict only or stimulus and response selection conflict) and utilized a novel modeling approach to isolate error and conflict variance during a multimodal numeric Stroop task. Specifically, hemodynamic response functions resulting from two statistical models that either included or isolated variance arising from relatively few error trials were directly contrasted. Twenty-four participants completed the task while undergoing event-related functional magnetic resonance imaging on a 1.5-Tesla scanner. Response times monotonically increased based on the presence of pure stimulus or stimulus and response selection conflict. Functional results indicated that dMFC activity was present during trials requiring response selection and inhibition of competing motor responses, but absent during trials involving pure stimulus conflict. A comparison of the different statistical models suggested that relatively few error trials contributed to a disproportionate amount of variance (i.e., activity) throughout the dMFC, but particularly within the rostral anterior cingulate gyrus (rACC). Finally, functional connectivity analyses indicated that an empirically derived seed in the dorsal ACC/pre-SMA exhibited strong connectivity (i.e., positive correlation) with prefrontal and inferior parietal cortex but was anti-correlated with the default-mode network. An empirically derived seed from the rACC exhibited the opposite pattern, suggesting that sub-regions of the dMFC exhibit different connectivity patterns with other large scale networks implicated in internal mentations such as daydreaming (default-mode) versus the execution of top-down attentional control (fronto-parietal). PMID- 21976412 TI - PTBP1-dependent regulation of USP5 alternative RNA splicing plays a role in glioblastoma tumorigenesis. AB - Aberrant RNA splicing is thought to play a key role in tumorigenesis. The assessment of its specific contributions is limited by the complexity of information derived from genome-wide array-based approaches. We describe how performing splicing factor-specific comparisons using both tumor and cell line data sets may more readily identify physiologically relevant tumor-specific splicing events. Affymetrix exon array data derived from glioblastoma (GBM) tumor samples with defined polypyrimidine tract-binding protein 1 (PTBP1) levels were compared with data from U251 GBM cells with and without PTBP1 knockdown. This comparison yielded overlapping gene sets that comprised only a minor fraction of each data set. The identification of a novel GBM-specific splicing event involving the USP5 gene led us to further examine its role in tumorigenesis. In GBM, USP5 generates a shorter isoform 2 through recognition of a 5' splice site within exon 15. Production of the USP5 isoform 2 was strongly correlated with PTBP1 expression in GBM tumor samples and cell lines. Splicing regulation was consistent with the presence of an intronic PTBP1 binding site and could be modulated through antisense targeting of the isoform 2 splice site to force expression of isoform 1 in GBM cells. The forced expression of USP5 isoform 1 in two GBM cell lines inhibited cell growth and migration, implying an important role for USP5 splicing in gliomagenesis. These results support a role for aberrant RNA splicing in tumorigenesis and suggest that changes in relatively few genes may be sufficient to drive the process. PMID- 21976413 TI - Calix[4]pyrrole-calix[4]arene-crown-5 conjugate with flexible linkers as a model for a selective ion-pair container. PMID- 21976414 TI - Effects of di(2-ethylhexyl)phthalate on testicular oxidant/antioxidant status in selenium-deficient and selenium-supplemented rats. AB - Di(ethylhexyl)phthalate (DEHP), the most widely used plasticizer, was investigated to determine whether an oxidative stress process was one of the underlying mechanisms for its testicular toxicity potential. To evaluate the effects of selenium (Se), status on the toxicity of DEHP was further objective of this study, as Se is known to play a critical role in testis and in the modulation of intracellular redox equilibrium. Se deficiency was produced in 3 weeks-old Sprague-Dawley rats feeding them <=0.05 mg Se /kg diet for 5 weeks, and Se-supplementation group was on 1 mg Se/kg diet. DEHP-treated groups received 1000 mg/kg dose by gavage during the last 10 days of the feeding period. Activities of antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), glutathione peroxidase 4 (GPx4), thioredoxin reductase (TrxR)], catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST); concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), and thus the GSH/GSSG redox ratio; and thiobarbituric acid reactive substance (TBARS) levels were measured. DEHP was found to induce oxidative stress in rat testis, as evidenced by significant decrease in GSH/GSSG redox ratio (>10-fold) and marked increase in TBARS levels, and its effects were more pronounced in Se-deficient rats with ~18.5-fold decrease in GSH/GSSG redox ratio and a significant decrease in GPx4 activity, whereas Se supplementation was protective by providing substantial elevation of redox ratio and reducing the lipid peroxidation. These findings emphasized the critical role of Se as an effective redox regulator and the importance of Se status in protecting testicular tissue from the oxidant stressor activity of DEHP. PMID- 21976415 TI - Pericyclic cascade with chirality transfer: reaction pathway and origin of enantioselectivity of the hetero-Claisen approach to oxindoles. PMID- 21976416 TI - Residential segregation and disparities in health care services utilization. AB - Using data from the 2006 Medical Expenditure Panel Survey and the 2000 Census, the authors explored whether race/ethnic disparities in health care use were associated with residential segregation. They used five measures of health care use: office-based physician visits, outpatient department physician visits, visits to nurses and physician's assistants, visits to other health professionals, and having a usual source of care. For each individual, the authors controlled for age, gender, marital status, insurance status, income, educational attainment, employment status, region, and health status. The authors used the racial-ethnic composition of the zip code to control for residential segregation. The findings suggest that disparities in health care utilization are related to both individuals' racial and ethnic identity and the racial and ethnic composition of their communities. Therefore, efforts to improve access to health care services and to eliminate health care disparities for African Americans and Hispanics should not only focus on individual-level factors but also include community-level factors. PMID- 21976417 TI - Patient mix in outpatient surgery settings and implications for Medicare payment policy. AB - In 2008, Medicare implemented a new payment policy for ambulatory surgical centers (ASCs), which aligns the ASC payment system with that used for hospital outpatient departments and reimburses ASCs approximately 65% of what hospitals receive for the same outpatient surgery. The authors assess patient selection across ASCs and hospital outpatient departments for four common surgeries (colonoscopy, hernia repair, knee arthroscopy, cataract repair), using data on procedures performed in Florida from 2004 to 2008. The authors construct measures of patient illness severity and cost risk and find that ASCs benefit from positive selection. Nonetheless, the degree of selection varies by surgery type and patient population. While similar studies in other states are needed, the findings suggest that modifications to the Medicare outpatient payment system may be appropriate to account for the different populations that each setting attracts. PMID- 21976419 TI - New insights into the influence of cigarette smoking on urothelial carcinogenesis: smoking-induced gene expression in tumor-free urothelium might discriminate muscle-invasive from nonmuscle-invasive urothelial bladder cancer. AB - Smoking is the main risk factor for urothelial bladder cancer. In former smokers the risk decreases but does not reach the low level of never smokers. This indicates reversible and permanent smoking-derived genetic alterations. Transcriptional changes may point to mechanisms, how smoking promotes urothelial bladder cancer. To identify smoking-derived transcriptional changes we performed gene expression profiling in current, former, and never smokers, using tumor and tumor-free urothelium from patients with nonmuscle-invasive urothelial bladder cancer (NMIBC) or muscle-invasive urothelial bladder cancer (MIBC). Smoking turned out to influence gene expression much less than tumor stage (NMIBC or MIBC) and tumor transformation (tumor-free or tumor). Smoking seemed to influence gene expression in patients with MIBC more strongly compared to those with NMIBC. The least irreversible changes after smoking cessation were proposed in tumor free urothelium from patients with NMIBC. Growth factors and oncogenes were up regulated in tumor-free urothelium from smokers with MIBC but not from smokers with NMIBC. A panel of genes up-regulated in smokers have potential for early detection and distinction of MIBC from NMIBC using tumor-free tissue. PMID- 21976420 TI - RNA-Seq analysis in MeV. AB - SUMMARY: RNA-Seq is an exciting methodology that leverages the power of high throughput sequencing to measure RNA transcript counts at an unprecedented accuracy. However, the data generated from this process are extremely large and biologist-friendly tools with which to analyze it are sorely lacking. MultiExperiment Viewer (MeV) is a Java-based desktop application that allows advanced analysis of gene expression data through an intuitive graphical user interface. Here, we report a significant enhancement to MeV that allows analysis of RNA-Seq data with these familiar, powerful tools. We also report the addition to MeV of several RNA-Seq-specific functions, addressing the differences in analysis requirements between this data type and traditional gene expression data. These tools include automatic conversion functions from raw count data to processed RPKM or FPKM values and differential expression detection and functional annotation enrichment detection based on published methods. PMID- 21976418 TI - Optimized neural coding? Control mechanisms in large cortical networks implemented by connectivity changes. AB - Using functional magnetic resonance imaging, we show that a distributed fronto parietal visuomotor integration network is recruited to overcome automatic responses to both biological and nonbiological cues. Activity levels in these areas are similar for both cue types. The functional connectivity of this network, however, reveals differential coupling with thalamus and precuneus (biological cues) and extrastriate cortex (nonbiological cues). This suggests that a set of cortical areas equally activated in two tasks may accomplish task goals differently depending on their network interactions. This supports models of brain organization that emphasize efficient coding through changing patterns of integration between regions of specialized function. PMID- 21976421 TI - A non-biased framework for the annotation and classification of the non-miRNA small RNA transcriptome. AB - MOTIVATION: Recent progress in high-throughput sequencing technologies has largely contributed to reveal a highly complex landscape of small non-coding RNAs (sRNAs), including novel non-canonical sRNAs derived from long non-coding RNA, repeated elements, transcription start sites and splicing site regions among others. The published frameworks for sRNA data analysis are focused on miRNA detection and prediction, ignoring further information in the dataset. As a consequence, tools for the identification and classification of the sRNAs not belonging to miRNA family are currently lacking. RESULTS: Here, we present, SeqCluster, an extension of the currently available SeqBuster tool to identify and analyze at different levels the sRNAs not annotated or predicted as miRNAs. This new module deals with sequences mapping onto multiple locations and permits a highly versatile and user-friendly interaction with the data in order to easily classify sRNA sequences with a putative functional importance. We were able to detect all known classes of sRNAs described to date using SeqCluster with different sRNA datasets. PMID- 21976422 TI - Probabilistic alignments with quality scores: an application to short-read mapping toward accurate SNP/indel detection. AB - MOTIVATION: Recent studies have revealed the importance of considering quality scores of reads generated by next-generation sequence (NGS) platforms in various downstream analyses. It is also known that probabilistic alignments based on marginal probabilities (e.g. aligned-column and/or gap probabilities) provide more accurate alignment than conventional maximum score-based alignment. There exists, however, no study about probabilistic alignment that considers quality scores explicitly, although the method is expected to be useful in SNP/indel callers and bisulfite mapping, because accurate estimation of aligned columns or gaps is important in those analyses. RESULTS: In this study, we propose methods of probabilistic alignment that consider quality scores of (one of) the sequences as well as a usual score matrix. The method is based on posterior decoding techniques in which various marginal probabilities are computed from a probabilistic model of alignments with quality scores, and can arbitrarily trade off sensitivity and positive predictive value (PPV) of prediction (aligned columns and gaps). The method is directly applicable to read mapping (alignment) toward accurate detection of SNPs and indels. Several computational experiments indicated that probabilistic alignments can estimate aligned columns and gaps accurately, compared with other mapping algorithms e.g. SHRiMP2, Stampy, BWA and Novoalign. The study also suggested that our approach yields favorable precision for SNP/indel calling. PMID- 21976423 TI - DroPhEA: Drosophila phenotype enrichment analysis for insect functional genomics. AB - SUMMARY: DroPhEA is a core module of a web application that facilitates research in insect functional genomics through enrichment analysis on mutant phenotypes of fruit fly (Drosophila melanogaster). The phenotypes investigated in the analyses can be predefined by FlyBase or customized by users. DroPhEA allows users to specify mutation or ortholog types, displays enriched term results in a hierarchical structure and supports analyses on gene sets of all insect species with a fully sequenced genome. PMID- 21976425 TI - Ischemia driven percutaneous coronary intervention for chronic total occlusions - is there light at the end of the tunnel? PMID- 21976424 TI - Hindered submicron mobility and long-term storage of presynaptic dense-core granules revealed by single-particle tracking. AB - Dense-core granules (DCGs) are organelles found in neuroendocrine cells and neurons that house, transport, and release a number of important peptides and proteins. In neurons, DCG cargo can include the secreted neuromodulatory proteins tissue plasminogen activator (tPA) and/or brain-derived neurotrophic factor (BDNF), which play a key role in modulating synaptic efficacy in the hippocampus. This function has spurred interest in DCGs that localize to synaptic contacts between hippocampal neurons, and several studies recently have established that DCGs localize to, and undergo regulated exocytosis from, postsynaptic sites. To complement this work, we have studied presynaptically localized DCGs in hippocampal neurons, which are much more poorly understood than their postsynaptic analogs. Moreover, to enhance relevance, we visualized DCGs via fluorescence labeling of exogenous and endogenous tPA and BDNF. Using single particle tracking, we determined trajectories of more than 150 presynaptically localized DCGs. These trajectories reveal that mobility of DCGs in presynaptic boutons is highly hindered and that storage is long-lived. We also computed mean squared displacement curves, which can be used to elucidate mechanisms of transport. Over shorter time windows, most curves are linear, demonstrating that DCG transport in boutons is driven predominantly by diffusion. The remaining curves plateau with time, consistent with motion constrained by a submicron-sized corral. These results have relevance to recent models of presynaptic organization and to recent hypotheses about DCG cargo function. The results also provide estimates for transit times to the presynaptic plasma membrane that are consistent with measured times for onset of neurotrophin release from synaptically localized DCGs. PMID- 21976426 TI - The value of recanalizing a chronic total occlusion. PMID- 21976427 TI - Crossing the "balloon uncrossable" chronic total occlusion: Tornus to the rescue. PMID- 21976428 TI - Navigating through tiny rivers. PMID- 21976429 TI - Optimizing outcomes with a pharmacoinvasive strategy: is there a role for glycoprotein IIb/IIIa receptor antagonists? PMID- 21976430 TI - Performance curves: applied science of proficiency. PMID- 21976431 TI - Total aorto-ostial chronic occlusion of the right coronary artery successfully recanalized via retrograde approach. AB - Chronic total occlusions remain a technical challenge for interventional cardiologists. This group of lesions carries a decreased rate of success and continues to be an important reason for surgical revascularization. Recently, retrograde percutaneous coronary intervention of total occlusions via epicardial and septal perforators was introduced as an alternative approach when a previous antegrade attempt has failed. We describe a unique case where retrograde approach was used as the initial recanalization technique in the absence of a right coronary ostium. PMID- 21976432 TI - Innovative resource utilization to fashion individualized covered stents in the setting of aortic coarctation. AB - OBJECTIVES: We describe our experience with self-fabricated covered stents in the setting of coarctation of the aorta (CoA). BACKGROUND: Balloon-expandable covered stents are increasingly being utilized to treat CoA in older children and adults. These stents however, are not available in the United States limiting the interventionalist's ability to treat this condition safely and effectively. METHODS: Retrospective analysis and follow-up data review of our complete experience with self-fabricated covered stents for CoA. Stents were fashioned by suturing an appropriate length of tubular polytetraflouroethylene to a bare metal stent and deploying this stent across the coarctation in a standardized fashion. RESULTS: Over a 9-year period we implanted 53 balloon-expandable stents in 49 patients with CoA. Of these 13 were self-fabricated covered stents deployed in 13 patients (7 male). Median age at implantation was 25.4 years (range, 8.7-49.5 years) with median weight of 65.5 kg (range, 28-168 kg). Indications for stent placement were native coarctation/aortic atresia (n = 9), aneurysm formation (n = 3), and re-coarctation (n = 1). The median systolic pressure gradient across the coarctation of 33 mm Hg (range, 12-69 mm Hg) was reduced to 3 mm Hg (range, 0-19 mm Hg) post procedure (P < 0.001). There were no deaths on median follow-up of 44 months (range, 1-83 months). One patient developed acute contained extravasation at implantation, treated with a self-expanding stent graft. Another patient required thrombectomy for femoral arterial thrombosis. CONCLUSIONS: Innovative application of available materials adds to the armamentarium of the interventionalist. Our self-fabricated covered stent provides effective gradient reduction with no compromise in stent delivery or durability on follow-up. PMID- 21976433 TI - Post TAVI paravalvular regurgitation: can we stop the leak? PMID- 21976434 TI - Can you fit a round peg in a square hole? #2. PMID- 21976435 TI - Inhibition of chlamydial class Ic ribonucleotide reductase by C-terminal peptides from protein R2. AB - Chlamydia trachomatis ribonucleotide reductase (RNR) is a class Ic RNR. It has two homodimeric subunits: proteins R1 and R2. Class Ic protein R2 in its most active form has a manganese-iron metal cofactor, which functions in catalysis like the tyrosyl radical in classical class Ia and Ib RNRs. Oligopeptides with the same sequence as the C-terminus of C. trachomatis protein R2 inhibit the catalytic activity of C. trachomatis RNR, showing that the class Ic enzyme shares a similar highly specific inhibition mechanism with the previously studied radical-containing class Ia and Ib RNRs. The results indicate that the catalytic mechanism of this class of RNRs with a manganese-iron cofactor is similar to that of the tyrosyl-radical-containing RNRs, involving reversible long-range radical transfer between proteins R1 and R2. The competitive binding of the inhibitory R2 derived oligopeptide blocks the transfer pathway. We have constructed three dimensional structure models of C. trachomatis protein R1, based on homologous R1 crystal structures, and used them to discuss possible binding modes of the peptide to protein R1. Typical half maximal inhibitory concentration values for C. trachomatis RNR are about 200 u m for a 20-mer peptide, indicating a less efficient inhibition compared with those for an equally long peptide in the Escherichia coli class Ia RNR. A possible explanation is that the C. trachomatis R1/R2 complex has other important interactions, in addition to the binding mediated by the R1 interaction with the C-terminus of protein R2. PMID- 21976436 TI - Condensation approach to aliphatic oligourea foldamers: helices with N (pyrrolidin-2-ylmethyl)ureido junctions. PMID- 21976437 TI - Associations of lifestyle-related factors, hsa-miR-149 and hsa-miR-605 gene polymorphisms with gastrointestinal cancer risk. AB - To explore the associations of SNPs within hsa-miR-605 (rs2043556) and hsa-miR 149 (rs2292832) and lifestyle-related factors with gastrointestinal cancer, a case-control study including 762 cases and 757 controls was conducted. Marginally significant associations were found both for hsa-miR-149 rs2292832 with gastric cancer risk (TC + CC vs. TT, OR = 0.68, 95% CI: 0.44-1.04) and for hsa-miR-605 rs2043556 with colorectal cancer risk (AG + GG vs. AA, OR = 0.70, 95% CI: 0.48 1.02) in males. Tea drinking showed a protective effect on gastric cancer risk (OR = 0.28, 95% CI: 0.13-0.60), while smoke inhalation increased the risk of gastric cancer (OR = 1.94, 95% CI: 1.08-3.47). Irritability was found to be a risk factor for both colorectal cancer (OR = 1.61, 95% CI: 1.02-2.53) and gastric cancer (OR = 1.96, 95% CI: 1.17-3.29). Among those that engaged in smoke inhalation, miR-149 CT/CC and miR-605 AG/GG genotype carriers had increased susceptibilities to colorectal cancer (OR = 1.90, 95% CI: 1.11-3.25) and gastric cancer (OR = 1.87, 95% CI: 1.03-3.42), respectively. Among the tea drinkers, there exists a marginally protective effect of miR-605 AG/GG genotypes on colorectal cancer incidence (OR = 0.71, 95% CI: 0.47-1.06) and a significantly protective effect of miR-149 CT/CC on gastric cancer incidence (OR = 0.47, 95% CI: 0.29-0.77). The SNPs of rs2292832 and rs2043556 might be able to modify the susceptibility to male gastric and colorectal cancers, respectively. Tea drinking is a protective factor, while smoke inhalation is a risk factor for gastric cancer, and they might have the potential to modify the associations between miR 149 and miR-605 polymorphisms with gastrointestinal cancer risk. In addition, irritability was shown to be a risk factor for both gastric and colorectal cancers. PMID- 21976439 TI - Calvaria bone chamber--a new model for intravital assessment of osseous angiogenesis. AB - The faith of tissue engineered bone replacing constructs depends on their early supply with oxygen and nutrients, and thus on a rapid vascularization. Although some models for direct observation of angiogenesis are described, none of them allows the observation of new vessel formation in desmal bone. Therefore, we developed a new chamber model suitable for quantitative in vivo assessment of the vascularization of bone substitutes by intravital fluorescence microscopy. In the parietal calvaria of 32 balb/c mice a critical size defect was set. Porous 3D poly(L-lactide-co-glycolide) (PLGA)-blocks were inserted into 16 osseous defects (groups 3 and 4) while other 16 osseous defects remained unequipped (groups 1 and 2). By placing a polyethylene membrane onto the dura mater, the angiogenesis was mainly restricted to the osseous margins (groups 2 and 4). Microvascular density, angiogenesis, and microcirculatory parameters were evaluated repetitively during 22 days. In all animals, only a mild inflammatory reaction was observed with a climax after 2 weeks. The implantation of PLGA scaffolds resulted in a vascular growth directed towards the center of the defect as demonstrated by the significantly (p < 0.05) enhanced central microvascular densitiy from day 3 to day 22 when compared with unequipped chambers. The additional application of polyethylene membrane was found to reduce significantly the microvessel density mainly in the center of both scaffolds and defects. The present calvaria bone chamber allows for the first time to assess quantitatively the angiogenesis arising from desmal bone directly in vivo. Therefore, this chronic model may support the future research in the biological adequacy of bone substitutes. PMID- 21976440 TI - Enhanced Schwann cell adhesion and elongation on a topographically and chemically modified poly(L-lactic acid) film surface. AB - A dense poly-L-lactic acid (PLLA) film was employed as the primary material and hot-embossed with the formation of microgrooves (g-PLLA). A thin layer of Au was then deposited on the film to obtain a morphologically modified substrate (Au/g PLLA). The Au/g-PLLA film surface was then chemically modified by imprinting octadecanethiolate (ODT) self-assembled monolayers on the upper surface (ODT/Au/g PLLA), followed by Arg-Gly-Asp (RGD) peptide sequences on the microgrooves (RGD_ODT/Au/g-PLLA). The surface chemistry of the as-prepared RGD_ODT/Au/g-PLLA samples was examined. The bioactivity and spreading function of Schwann cells cultured on the morphologically and chemically modified surfaces were assessed. The results demonstrate that Schwann cells adhered to the RGD/Au/g-PLLA surface and proliferated along the microgrooves without crossing over the ODT/Au/PLLA surface. The proposed film surface can be used for manipulating the outgrowth of axons by modifying and arranging a selected region to induce cell growth and to prevent cells from spreading out nondirectionally. PMID- 21976438 TI - Primary cilia and Gli3 activity regulate cerebral cortical size. AB - During neural development patterning, neurogenesis, and overall growth are highly regulated and coordinated between different brain regions. Here, we show that primary cilia and the regulation of Gli activity are necessary for the normal expansion of the cerebral cortex. We show that loss of Kif3a, an important functional component of primary cilia, leads to the degeneration of primary cilia, marked overgrowth of the cortex, and altered cell cycle kinetics within cortical progenitors. The G1 phase of the cell cycle is shortened through a mechanism likely involving reduced Gli3 activity and a resulting increase in expression of cyclin D1 and Fgf15. The defects in Gli3 activity alone are sufficient to accelerate cell cycle kinetics and cause the molecular changes seen in brains that lack cilia. Finally, we show that levels of full-length and repressor Gli3 proteins are tightly regulated during normal development and correlate with changes in expression of two known Shh-target genes, CyclinD1 and Fgf15, and with the normal lengthening of the cell cycle during corticogenesis. These data suggest that Gli3 activity is regulated through the primary cilium to control cell cycle length in the cortex and thus determine cortical size. PMID- 21976441 TI - Improved blood compatibility of Mg-1.0Zn-1.0Ca alloy by micro-arc oxidation. AB - Magnesium and its alloys have been used in the recent development of lightweight, biodegradeable implant materials. However, the corrosion properties of magnesium limit its usefulness. In a previous study, a micro-arc oxidation (MAO) method was used to modify a Mg-1.0 wt % Zn-1.0 wt % Ca alloy surface, with the purpose of improving the corrosion resistance of Mg alloys. However, the blood compatibility of MAO-treated Mg alloy is unknown. Results of cytotoxicity assays with bone marrow-derived mesenchymal stem cells showed that extracts of MAO-treated alloy significantly decreased cytotoxicity compared to titanium alloy extract. Results of blood compatibility tests showed that the MAO group had a decreased hemolytic ratio (2.25%) compared to the untreated Mg alloy group (24.58%) (p < 0.001). The MAO group showed significantly shorter prothrombin and thrombin times and significantly longer activated partial thromboplastin time than the untreated Mg alloy group. Arachidonic acid- and adenosine diphosphate-induced platelet aggregations were significantly decreased by the untreated Mg alloy extract, and they were less affected by extract of MAO-treated Mg alloy. In conclusion, MAO treated Mg-1.0 wt % Zn-1.0 wt % Ca alloy exhibits favorable blood compatibility characteristics and may be useful in the development of magnesium implant materials. PMID- 21976442 TI - Synthesis of calcium-silica composites: a route toward an in vitro model system for calcific band keratopathy precipitates. AB - Calcific band keratopathy (CBK) is a degenerative condition resulting in the deposition of calcium salts in the superficial layers of the cornea and causing significant visual disturbance and pain of the affected eye. Unfortunately, the amount of CBK precipitates recovered from the affected eye is very small therefore; it would be beneficial to prepare a synthetic material mimicking CBK material to further the development of therapeutics. Analyses of biological samples recovered from patients show the presence of silicon in addition to calcium, as well as a distinctive fused spherical morphology. This prompted us to study the reaction of various sources of silicon (fumed silica, silicic acid, and silicone oil) with CaCO(3) under a range of reaction conditions to gain an understanding of the formation of CBK. A silicon source alone was not found to be responsible for the fused spherical morphology, and a third component, a polar surfactant-like molecule such as sodium dodecyl sulfate or tetradecylphosphonic acid, was also required. The effects of silicon:calcium ratio and reaction time have been studied. The reaction of fumed silica with CaCO(3) in presence of sodium dodecyl sulfate results in the formation of spherical shapes resembling the structures and chemical composition observed in the eye samples, while no such structures were observed in the absence of silicon. Samples closely resembling human samples were also formed from the reaction of silicone oil with CaCO(3) in the presence of tetradecylphosphonic acid. Samples were characterized by SEM, XRD, and XPS and Raman spectroscopy. PMID- 21976443 TI - Tuning of the pro-oxidant and antioxidant activity of trolox through the controlled release from biodegradable poly(trolox ester) polymers. AB - In a variety of biomedical applications (e.g., tissue engineering, drug delivery, etc.), the role of a bioactive material is to serve as a platform by which one can modulate the cellular response into a desired role. Of the methods by which one may achieve this control (e.g., shape, structure, binding, growth factor release), the control of the cellular redox state has been under evaluated. Ideally, the ability to tune the redox state of a cell provides an additional level of control over a variety of cellular responses including, cell differentiation, proliferation, and apoptosis. Yet, in order to achieve such control, it is important to know both the overall oxidative status of the cell and what molecular targets are being oxidized. In this work, poly (trolox ester) nanoparticles were evaluated for their ability to either inhibit or induce cellular oxidative stress in a dose-dependent fashion. This polymer delivery form possessed a unique ability to suppress protein oxidation, a feature not seen in the free drug form, emphasizing the advantage of the delivery/dosage formulation has upon regulating cellular response. PMID- 21976444 TI - The biocompatibility and antimicrobial activity of nanocomposites from polyurethane and nano silicate platelets. AB - Nanocomposites from a polyether-type waterborne polyurethane (PU) and 0.1 wt % of silicate materials were prepared. The individual silicate materials were natural clays (montmorillonite and mica), their exfoliated clays [nano silicate platelets (NSP) and nano mica platelets], and NSP modified with C18 fatty amine (NSP-S). The physico-chemcical properties and antimicrobial activity of the nanocomposites were characterized in vitro. The biostability and biocompatibility of the nanocomposites were evaluated in vivo. The nanocomposites exhibited various surface morphologies with phase separation of hard and soft domains in nanometric scales. The nanocomposite containing NSP (PU-NSP) showed better endothelial cell attachment and gene expression. The better biocompatibility of PU-NSP and PU-NSP S was evidenced by the lower thickness of foreign body capsules in rat subcutaneous implantation. PU-NSP had the least surface degradation in vivo as demonstrated by the electron microscopy and infrared spectroscopy. This may be associated with the different surface structure. PU-NSP and PU-NSP-S showed strong bacteriostatic effects, which suggested that the nano clay in the polymer matrix may still interact with the microbes. PMID- 21976445 TI - Maintenance of hepatic differentiation by hepatocyte attachment peptides derived from laminin chains. AB - Hepatocytes rapidly lose hepatic functions upon isolation from liver, perhaps due to disrupted cell/matrix interactions. The matrix macromolecule laminin-111 consists of three chains, alpha1, beta1, and gamma1; it is a major component of Matrigel, which can maintain hepatic differentiation. We previously showed that the A13 peptide (RQVFQVAYIIIKA, alpha1 chain 121-133) derived from mouse laminin alpha1 exhibits hepatocyte attachment activity and maintains hepatic differentiation. Here, we sought to identify hepatocyte adhesive sequences from the mouse laminin beta1 and gamma1 chains using 22 synthetic peptides that show biological activity for fibrosarcoma cells. Nine peptides showed hepatocyte attachment activity. Of these, B160 (VILQQSAADIAR, beta1 chain 1607-1618), and C16 (KAFDITYVRLKF gamma1 chain 139-150) exhibited the most potent activity. Hepatocytes cultured on both peptides also maintained expression of albumin, tyrosine aminotransferase, tryptophan-2,3-dioxygenase, and cytochrome P450. The morphology of hepatocytes on both peptides was a rounded shape typical for hepatic differentiation. We also characterized the nature of adhesion to the peptides. Heparin and EDTA inhibited cell attachment to both peptides, suggesting that hepatocyte attachment to the peptides was mediated by multiple receptors. The identification of active sequences regulating hepatic functions may facilitate the design of hepatocyte culture substrata that can regulate specific cellular behaviors in the context of a bioartificial liver. PMID- 21976446 TI - Perfusion culture enhanced human endometrial stromal cell growth in alginate multivalent integrin alpha5beta1 ligand scaffolds. AB - A method to functionalize alginate by introducing monomeric or self-assembling (tetrameric) fibronectin (FN) domains is described, leading to a functional scaffold, which is used for three dimensional (3D) culture of human endometrial stromal cells (EnSCs). EnSCs encapsulated in the functional alginate were cultured under perfusion using the TissueFlex(r) platform, a multiple parallel microbioreactor system for 3D cell culture. The effect of the novel scaffold and the effect of perfusion were examined. Cell viability, proliferation, and extracellular matrix (ECM) deposition were determined and the results compared with those obtained with cells encapsulated in non-functionalized alginate, and also those without perfusion. Staining for focal adhesions and actin showed maximal cell adhesion only for alginate-tetrameric FN scaffolds under perfusion, associated with a significant increase in cell number over 7 days culture; in contrast to poor cell adhesion and a decrease in cell number for non functionalized alginate scaffolds (irrespective of perfused/static culture) and 3D static culture (irrespective of the scaffold). Conjugation of alginate to FN was an absolute requirement to attenuate the loss of cell metabolic activity over 7 days culture. ECM deposition for blank alginate and alginate-monomeric FN was similar, but increased around 2-fold and 3-fold for alginate-tetrameric FN under static and perfusion culture, respectively. It is concluded that the requirement for EnSC engagement with multivalent integrin alpha5beta1 ligands and perfused culture are both essential as a first step toward endometrial tissue engineering. PMID- 21976447 TI - Mechanical characterization and biocompatibility of a novel reinforced fascia patch for rotator cuff repair. AB - To provide mechanical augmentation for rotator cuff repair, it is necessary (though perhaps not sufficient) that scaffolds have tendon-like material and suture retention properties, be applied to the repair in a surgically appropriate manner, and maintain their mechanical properties for an acceptable period of time following surgery. While allograft fascia lata has material, structural, and biochemical properties similar to tendon tissue, its poor suture retention properties abrogates its potential as an augmentation device. The goal of this work was to design a novel reinforced fascia patch with suture retention and stiffness properties adequate to provide mechanical augmentation for rotator cuff repair. Fascia was reinforced by stitching with PLLA or PLLA/PGA polymer braids. Reinforced fascia patches had a maximum construct load greater than (or equal to) the suture retention properties of human rotator cuff tendon (~250N) at time zero and after in vivo implantation for 12 weeks in a rat subcutaneous model. The patches were able to withstand the 2500 loading cycles projected for the early post-operative period. The patches also demonstrated biocompatibility with the host using a rat abdominal wall defect model. These studies suggest the potential use of reinforced fascia patches to provide mechanical augmentation, minimize tendon retraction and possibly reduce the incidence of rotator cuff repair failure. PMID- 21976448 TI - Polyamidoamine dendrimer-functionalized carbon nanotubes-mediated GFP gene transfection for HeLa cells: effects of different types of carbon nanotubes. AB - Three types of functionalized carbon nanotubes (f-CNTs), polyamidoamine (PAMAM) dendrimer-functionalized single and multi-walled CNTs (MWCNT-PAMAM-1, MWCNT-PAMAM 2, and SWCNT-PAMAM-3), were prepared by covalent linkage approach. The micro morphologies of the three f-CNTs and the interaction of MWCNT-PAMAM-2 with HeLa cells were characterized by transmission electron microscopy (TEM). The free amine groups on the surface of the three types of CNTs-PAMAM hybrids were quantitatively analyzed. Their cytotoxicity and transfection efficiency of plasmid DNA of enhanced green fluorescent protein (pEGFP-N1) to HeLa cells were investigated in detail. The results suggest that although all three types of CNTs PAMAM hybrids can deliver pEGFP-N1 into HeLa cells and the exogenous GFP gene has been successfully expressed, MWCNT-PAMAM-2 with shorter length and larger amount of free amine groups on its surface possesses higher transfection efficiency (6.79%), being about 3.0 and 1.7 times as large as those of MWCNT-PAMAM-1 (2.24%) and SWCNT-PAMAM-3 (4.08%), respectively; their cytotoxicity to HeLa cells decrease following the sequence of SWCNT-PAMAM-3 > MWCNT-PAMAM-2 > MWCNT-PAMAM-1. These results may be useful for understanding the effects of the chemical/physical properties of f-CNTs on their gene transfection efficiency and cytotoxicity, allowing for construction of promising CNT-based intracellular delivery vectors for gene therapy. PMID- 21976449 TI - Photo-crosslinkable cyanoacrylate bioadhesive: shrinkage kinetics, dynamic mechanical properties, and biocompatibility of adhesives containing TMPTMA and POSS nanostructures as crosslinking agents. AB - The study investigates the photo-polymerization shrinkage behavior, dynamic mechanical properties, and biocompatibility of cyanoacrylate bioadhesives containing POSS nanostructures and TMPTMA as crosslinking agents. Adhesives containing 2-octyl cyanoacrylate (2-OCA) and different percentages of POSS nanostructures and TMPTMA as crosslinking agents were prepared. The 1-phenyl-1, 2 propanedione (PPD) was incorporated as photo-initiator into the adhesive in 1.5, 3, and 4 wt %. The shrinkage strain of the specimens was measured using bonded disk technique. Shrinkage strain, shrinkage strain rate, maximum and time at maximum shrinkage strain rate were measured and compared. Mechanical properties of the adhesives were also studied using dynamic mechanical thermal analysis (DMTA). Biocompatibility of the adhesives was examined by MTT method. The results showed that shrinkage strain increased with increasing the initiator concentration up to 3 wt % in POSS-containing and 1.5 wt % in TMPTMA-containing specimens and plateaued out at higher concentrations. By increasing the crosslinking agent, shrinkage strain, and shrinkage strain rate increased and the time at maximum shrinkage strain rate decreased. The study indicates that the incorporation of crosslinking agents into the cyanoacrylate adhesives resulted in improved mechanical properties. Preliminary MTT studies also revealed better biocompatibility profile for the adhesives containing crosslinking agents comparing to the neat specimens. PMID- 21976450 TI - The effects of surface and biomolecules on magnesium degradation and mesenchymal stem cell adhesion. AB - A novel class of biodegradable metals, magnesium (Mg) and Mg-based alloys, has recently attracted much attention because of unique biodegradation and mechanical properties for medical applications. Ideally, Mg-based devices should degrade no faster than the degradation products can be eliminated efficiently from the body. Additionally, for orthopedic and maxillofacial applications, the implant integration with the surrounding bone is critical for its clinical success. Therefore, it is necessary to thoroughly characterize Mg surface and degradation and investigate how these characteristics influence its interactions with essential cells, for example, bone marrow derived mesenchymal stem cells. The objectives of this study were to investigate (1) the effects of two surface conditions (the presence vs. absence of surface oxides) on Mg degradation and mesenchymal stem cell adhesion, and (2) the effects of two essential aqueous environments (the presence vs. absence of physiological ions and proteins) on Mg degradation. In an effort towards standardizing testing methods for Mg alloys, consistent and well-controlled experimental methods were designed to characterize the surface and degradation of Mg and its interactions with cells. The results demonstrated that original surface (oxidized vs. polished) conditions had a less pronounced effect on regulating initial cell adhesion, but did affect surface morphology and composition of the Mg samples after 24 h of cell culture. The presence versus absence of biological ions and proteins had a significant effect on Mg degradation mode and rate. In conclusion, the material surface and anatomical sites of implantation dependent on the intended applications must be carefully considered while assessing Mg alloys in vitro or in vivo for medical applications. Standardized testing procedures and methods are critically needed for developing more effective medical-grade Mg alloys. PMID- 21976451 TI - In vivo toxicity of poly(propyleneimine) dendrimers. AB - Dendrimers are highly branched macromolecules with the potential to be used for biomedical applications. Several dendrimers are toxic owing to their positively charged surfaces. However, this toxicity can be reduced by coating these peripheral cationic groups with carbohydrate residues. In this study, the toxicity of three types of 4th generation poly (propyleneimine) dendrimers were investigated in vivo; uncoated (PPI-g4) dendrimers, and dendrimers in which 25% or 100% of surface amino groups were coated with maltotriose (PPI-g4-25%m or PPI g4-100%m), were administered to Wistar rats. Body weight, food and water consumption, and urine excretion were monitored daily. Blood was collected to investigate biochemical and hematological parameters, and the general condition and behavior of the animals were analyzed. Unmodified PPI dendrimers caused changes in the behavior of rats, a decrease in food and water consumption, and lower body weight gain. In the case of PPI-g4 and PPI-g4-25%m dendrimers, disturbances in urine and hematological and biochemical profiles returned to normal during the recovery period. PPI-g4-100%m was harmless to rats. The PPI dendrimers demonstrated dose- and sugar-modification-degree dependent toxicity. A higher dose of uncoated PPI dendrimers caused toxicity, but surface modification almost completely abolished this toxic effect. PMID- 21976452 TI - Asymmetric N-H insertion reaction cooperatively catalyzed by rhodium and chiral spiro phosphoric acids. PMID- 21976453 TI - Enantioselective rhodium(I)-catalyzed [3+2] annulations of aromatic ketimines induced by directed C-H activations. PMID- 21976454 TI - A broad range of ophthalmologic anomalies is part of the holoprosencephaly spectrum. AB - Holoprosencephaly (HPE) is the most common disorder of the developing forebrain in humans, and is characterized by failed or incomplete cleavage of the cerebral hemispheres and deep brain structures. HPE includes wide phenotypic variability, with a continuum of both brain and craniofacial anomalies. While "classic" eye findings, including the spectrum of midline anomalies ranging from cyclopia to hypotelorism, as well as chorioretinal coloboma and microphthalmia, have been frequently described in patients with HPE, other subtle eye anomalies may also occur. In our study we prospectively analyzed a small cohort of 10 patients in whom we identified mutations in SHH, SIX3, ZIC2, or FGF8, the latter of which is a very recently described HPE-associated gene. We found that 9 of 10 patients had at least two ophthalmologic anomalies, including refractive errors, microcornea, microphthalmia, blepharoptosis, exotropia, and uveal coloboma. These findings contribute to the understanding of the phenotypic variability of the HPE spectrum, and highlight findings in one medically important but often incompletely investigated system. PMID- 21976456 TI - Qualitative assessment of study materials and communication strategies used in studies that include DNA collection. AB - To understand motivations and barriers to participation in studies that include DNA collection, focus group discussions were held with mothers who had participated in a case-control study of birth defects. Recruited mothers had completed an interview and had received a mailed kit containing cytobrushes to collect buccal cells for DNA from herself, her infant, and her infant's father. Six moderator-led focus groups were attended by a total of 38 women residing in Atlanta, Georgia. Focus groups were segmented by DNA collection status (biologics participants or nonparticipants), infant case-control status, infant birthweight, and maternal race and ethnicity. This report assesses maternal attitudes toward study materials and communication strategies. Across groups, respondents expressed concern about how their contact information was obtained. Study materials were described as clear and professional by most women, although some respondents reported confusion about disclosure of individual genetic results. Respondents generally reported that monetary incentives were not a motivation to participate, but increased perceived study legitimacy. Biologics nonparticipants expressed concerns about kit component sterility; government involvement; and DNA sample use, storage, and disposal. Respondents suggested that investigators provide feedback on whether sample collection was performed correctly and provide materials targeted to fathers to help alleviate paternal skepticism. Participation in DNA collection might be improved by strengthening study materials and communication strategies. PMID- 21976455 TI - Electroconvulsive seizure promotes spine maturation in newborn dentate granule cells in adult rat. AB - Neurogenesis continues in the dentate gyrus of the hippocampus throughout life in mammals. This process is influenced by daily activities such as exercise, learning, and stress and may contribute to certain forms of hippocampus-dependent learning and memory. Adult hippocampal neurogenesis is also subject to regulation by antidepressant treatment, including chronic treatment with antidepressant drugs or electroconvulsive seizure (ECS) therapy. Here we investigated how the connectivity of newborn and mature granule cells is influenced by ECS administration in rats. Specifically, we examined the dendritic spine morphology of newborn and mature granule cells in rats and found that ECS administration promoted the maturation of dendritic spines in newborn cells and increased spine density in mature cells. These changes could potentially lead to alteration in dentate circuitry and may partially contribute to the functional effects of ECS. PMID- 21976457 TI - Virtual cerebral ventricular system: an MR-based three-dimensional computer model. AB - The inherent spatial complexity of the human cerebral ventricular system, coupled with its deep position within the brain, poses a problem for conceptualizing its anatomy. Cadaveric dissection, while considered the gold standard of anatomical learning, may be inadequate for learning the anatomy of the cerebral ventricular system; even with intricate dissection, ventricular structures remain difficult to observe. Three-dimensional (3D) computer reconstruction of the ventricular system offers a solution to this problem. This study aims to create an accurate 3D computer reconstruction of the ventricular system with surrounding structures, including the brain and cerebellum, using commercially available 3D rendering software. Magnetic resonance imaging (MRI) scans of a male cadaver were segmented using both semiautomatic and manual tools. Segmentation involves separating voxels of different grayscale values to highlight specific neural structures. User controls enable adding or removing of structures, altering their opacity, and making cross-sectional slices through the model to highlight inner structures. Complex physiologic concepts, such as the flow of cerebrospinal fluid, are also shown using the 3D model of the ventricular system through a video animation. The model can be projected stereoscopically, to increase depth perception and to emphasize spatial relationships between anatomical structures. This model is suited for both self-directed learning and classroom teaching of the 3D anatomical structure and spatial orientation of the ventricles, their connections, and their relation to adjacent neural and skeletal structures. PMID- 21976458 TI - In vivo flow cytometry of circulating clots using negative photothermal and photoacoustic contrasts. AB - Conventional photothermal (PT) and photoacousic (PA) imaging, spectroscopy, and cytometry are preferentially based on positive PT/PA effects, when signals are above background. Here, we introduce PT/PA technique based on detection of negative signals below background. Among various new applications, we propose label-free in vivo flow cytometry of circulating clots. No method has been developed for the early detection of clots of different compositions as a source of thromboembolism including ischemia at strokes and myocardial infarction. When a low-absorbing, platelet-rich clot passes a laser-irradiated vessel volume, a transient decrease in local absorption results in an ultrasharp negative PA hole in blood background. Using this phenomenon alone or in combination with positive contrasts, we demonstrated identification of white, red, and mixed clots on a mouse model of myocardial infarction and human blood. The concentration and size of clots were measured with threshold down to few clots in the entire circulation with size as low as 20 MUm. This multiparameter diagnostic platform using portable personal high-speed flow cytometer with negative dynamic contrast mode has potential to real-time defining risk factors for cardiovascular diseases, and for prognosis and prevention of stroke or use clot count as a marker of therapy efficacy. Possibility for label-free detection of platelets, leukocytes, tumor cells or targeting themby negative PA probes (e.g., nonabsorbing beads or bubbles) is also highlighted. PMID- 21976459 TI - Risk factors associated with complications and mortality in patients with Clostridium difficile infection. AB - BACKGROUND: Clostridium difficile infection (CDI) has increased in frequency and severity over the past decade. An understanding of the modifiable risk factors for disease severity has considerable clinical applicability. METHODS: We performed a retrospective case review of 485 cases in patients aged 1-99 years at the Naval Medical Center San Diego from November 2004 through December 2008. We compared potential risk factors for association with complications (megacolon, surgery, intensive care unit stay, and death) or mortality alone with use of univariable and multivariable logistic regression modeling. RESULTS: Forty-seven patients (9.8%) developed >=1 complication, and 23 (4.7%) died. We found independent associations between complications and acid suppression (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.2-4.79), admission for CDI (OR, 4.14; 95% CI, 2.17-7.92), older age (>=80 years; OR, 3.14; 95% CI, 1.46-6.73), and corticosteroid use (OR, 2.09; 95% CI, 1.01-4.35). Age >=80 years (OR, 5.51; 95% CI, 2.25-13.49) and acid suppression (OR, 4.74; 95% CI, 1.57-14.37) were associated with increased odds of death. CONCLUSIONS: Data published elsewhere have suggested that acid suppression therapy is a risk factor for CDI acquisition and relapse. These findings suggest an additional role in increased severity of disease, including mortality, and merit further study. PMID- 21976460 TI - Broad-range 16S rRNA gene polymerase chain reaction for diagnosis of culture negative bacterial infections. AB - BACKGROUND: Broad-range 16S ribosomal RNA (rRNA) gene polymerase chain reaction (PCR) is used for detection and identification of bacterial pathogens in clinical specimens from patients with a high suspicion for infection. However, prospective studies addressing the impact and clinical value of broad-range bacterial 16S rRNA gene amplification for diagnosis of acute infectious diseases in nonselected patient populations are lacking. METHODS: We first assessed the diagnostic performance of 16S rRNA gene PCR compared with routine bacterial culture. Second, we addressed prospectively the impact and clinical value of broad-range PCR for the diagnosis of acute infections using samples that tested negative by routine bacterial culture; the corresponding patients' data were evaluated by detailed medical record reviews. RESULTS: Results from 394 specimens showed a high concordance of >90% for 16S rRNA gene PCR and routine bacterial culture, indicating that the diagnostic performance of PCR for acute bacterial infections is comparable to that of bacterial culture, which is currently considered the gold standard. In thisprospective study, 231 specimens with a negative result on routine bacterial culture were analyzed with PCR, and patients' clinical data were reviewed. We found that broad-range 16S rRNA gene PCR showed a sensitivity, specificity, positive predictive value, and negative predictive value of 42.9%, 100%, 100%, and 80.2% for culture-negative bacterial infections. CONCLUSIONS: This study defines the role of 16S rRNA gene PCR for diagnosis of culture negative bacterial infections. Our data show that 16S rRNA gene PCR is particularly useful for identification of bacterial pathogens in patients pretreated with antibiotics. PMID- 21976461 TI - Revisiting the 1976 "swine flu" vaccine clinical trials: cross-reactive hemagglutinin and neuraminidase antibodies and their role in protection against the 2009 H1N1 pandemic virus in mice. AB - BACKGROUND: The 2009 H1N1 pandemic viruses are genetically similar to A/New Jersey/76 H1N1 virus (NJ/76), the strain selected for the 1976 "swine flu" vaccines. Approximately 45 million people in the United States were vaccinated against NJ/76 30 years ago, but the impact of this nationwide immunization on the current pandemic is largely unknown. METHODS: Archived human serum samples collected during the 1976 swine flu vaccine trials were assessed for cross reactive antibody responses to the 2009 H1N1 pandemic viruses. RESULTS: Administration of an NJ/76 monovalent vaccine or the combination of a bivalent vaccine (NJ/76 H1N1 and A/Victoria/75 H3N2) plus a B/Hong Kong/72 monovalent vaccine increased hemagglutinin inhibition (HAI) and neuraminidase inhibition (NAI) antibodies cross-reacting with the 2009 H1N1 pandemic viruses. We showed that cross-reactive human HAI antibodies elicited by the 1976 swine flu vaccination played a dominant role in protecting recipient mice against the wild type A/California/04/2009. Cross-reactive human NAI antibodies were also protective in recipient mice after a lethal challenge with a hemagglutinin mismatched virus bearing the A/California/04/2009 neuraminidase gene. Transfer of human serum samples with an original HAI titer of 43 or an original NAI titer of 472 was estimated to protect 50% of recipient mice from a lethal infection under the experimental conditions described. CONCLUSIONS: The 1976 swine flu vaccination induced cross-reactive HAI and NAI antibodies that were functionally protective in mice, suggesting that this vaccination campaign might have had a positive impact on older adults (>=50 years) in the United States during the 2009 H1N1 pandemic. PMID- 21976462 TI - Relapse versus reinfection: surveillance of Clostridium difficile infection. AB - Molecular typing was used to examine surveillance definitions for recurrent Clostridium difficile-associated diarrhea. Among 102 patients, 85 had a second episode within 8 weeks, 88% of which were relapses. Of 49 second episodes occurring after > 8 weeks, 65% were relapses. Categorization of a recurrent episode occurring after >8 weeks as a new infection may misrepresent the majority of episodes for surveillance. PMID- 21976463 TI - HIV infection, immune suppression, and uncontrolled viremia are associated with increased multimorbidity among aging injection drug users. AB - BACKGROUND: Despite an increasing burden of age-associated non-AIDS outcomes, few studies have investigated the prevalence or correlates of multimorbidity among aging human immunodeficiency virus (HIV)-infected and epidemiologically comparable at-risk populations. METHODS: Among 1262 AIDS Linked to the IntraVenous Experience (ALIVE) study participants followed in a community-based observational cohort, we defined the prevalence of 7 non-AIDS-defining chronic conditions (diabetes, obstructive lung disease, liver disease, anemia, obesity, kidney dysfunction, and hypertension) using clinical and laboratory criteria. Ordinal logistic regression was used to model the odds of increased multimorbidity associated with demographic, behavioral, and clinical factors. Self-reported prevalence was compared with clinically defined prevalence. RESULTS: Participants were a median of 48.9 years of age; 65.1% were male, 87.5% were African-American, and 28.7% were HIV infected. In multivariable analysis, HIV infection (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.13-1.99) was positively associated with increased multimorbidity. Among HIV-infected participants, multimorbidity was increased with lower nadir CD4 T-cell count (OR, 1.14 per 100-cell decrease; 95% CI, 1.00-1.29) and higher current HIV RNA (OR, 1.32 per log(10) increase; 95% CI, 1.08-1.60). Older age, being female, not using cigarettes or drugs, and having depressive symptoms were also associated with increased multimorbidity. A substantial proportion of multimorbid conditions in HIV-infected and HIV-uninfected participants were unrecognized and untreated. CONCLUSIONS: HIV-infected participants experienced increased numbers of multimorbid conditions; risk increased with advanced immunosuppression and higher viremia. These results underscore the heavy burden of multimorbidity associated with HIV and highlight the need for incorporating routine assessment and integrated management of chronic diseases as part of comprehensive healthcare for aging, HIV-infected persons. PMID- 21976464 TI - Mortality burden of the A/H1N1 pandemic in Mexico: a comparison of deaths and years of life lost to seasonal influenza. AB - BACKGROUND: The mortality burden of the 2009 A/H1N1 influenza pandemic remains controversial, in part because of delays in reporting of vital statistics that are traditionally used to measure influenza-related excess mortality. Here, we compare excess mortality rates and years of life lost (YLL) for pandemic and seasonal influenza in Mexico and evaluate laboratory-confirmed death reports. METHODS: Monthly age- and cause-specific death rates from January 2000 through April 2010 and population-based surveillance of influenza virus activity were used to estimate excess mortality and YLL in Mexico. Age-stratified laboratory confirmed A/H1N1 death reports were obtained from an active surveillance system covering 40% of the population. RESULTS: The A/H1N1 pandemic was associated with 11.1 excess all-cause deaths per 100,000 population and 445,000 YLL during the 3 waves of virus activity in Mexico, April-December 2009. The pandemic mortality burden was 0.6-2.6 times that of a typical influenza season and lower than that of the severe 2003-2004 influenza epidemic. Individuals aged 5-19 and 20-59 years were disproportionately affected relative to their experience with seasonal influenza. Laboratory-confirmed deaths captured 1 of 7 pandemic excess deaths overall but only 1 of 41 deaths in persons >60 years of age in 2009. A recrudescence of excess mortality was observed in older persons during winter 2010, in a period when influenza and respiratory syncytial virus cocirculated. CONCLUSIONS: Mexico experienced higher 2009 A/H1N1 pandemic mortality burden than other countries for which estimates are available. Further analyses of detailed vital statistics are required to assess geographical variation in the mortality patterns of this pandemic. PMID- 21976466 TI - The spectrum of engagement in HIV care: do more than 19% of HIV-infected persons in the US have undetectable viral load? PMID- 21976468 TI - Post-tsunami outbreaks of influenza in evacuation centers in Miyagi Prefecture, Japan. AB - We describe 2 post-tsunami outbreaks of influenza A in evacuation centers in Miyagi Prefecture, Japan, in 2011. Although containment of the outbreak was challenging in the evacuation settings, prompt implementation of a systemic approach with a bundle of control measures was important to control the influenza outbreaks. PMID- 21976467 TI - Pre-exposure prophylaxis and antiretroviral resistance: HIV prevention at a cost? AB - Pre-exposure prophylaxis (PrEP), the use of antiretrovirals (ARVs) by human immunodeficiency virus (HIV)-uninfected individuals to prevent acquisition of the virus during high-risk sexual encounters, enjoyed its first 2 major successes with the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 and the Pre-Exposure Prophylaxis Initiative (iPrEx). These successes were buoyed by additional positive results from the TDF2 and Partners PrEP trials. Although no seroconverters in either arm of CAPRISA developed resistance to tenofovir, 2 participants in iPrEx with undetected, seronegative acute HIV infection were randomized to receive daily oral tenofovir-emtricitabine and resistance to emtricitabine was later discovered in both men. A similar case in the TDF2 study resulted in resistance to both ARVs. These cases prompted us to examine existing literature on the nature of resistance mutations elicited by ARVs used for PrEP. Here, we discuss the impact of signature mutations selected by PrEP, how rapidly these emerge with daily ARV exposure, and the individual-level and public health consequences of ARV resistance. PMID- 21976469 TI - Quantifying cardiac hemodynamic stress and cardiomyocyte damage in ischemic and nonischemic acute heart failure. AB - BACKGROUND: The early and noninvasive differentiation of ischemic and nonischemic acute heart failure (AHF) in the emergency department (ED) is an unmet clinical need. METHODS AND RESULTS: We quantified cardiac hemodynamic stress using B-type natriuretic peptide (BNP) and cardiomyocyte damage using 2 different cardiac troponin assays in 718 consecutive patients presenting to the ED with AHF (derivation cohort). The diagnosis of ischemic AHF was adjudicated using all information, including coronary angiography. Findings were validated in a second independent multicenter cohort (326 AHF patients). Among the 718 patients, 400 (56%) were adjudicated to have ischemic AHF. BNP levels were significantly higher in ischemic compared with nonischemic AHF (1097 [604-1525] pg/mL versus 800 [427 1317] pg/mL; P<0.001). Cardiac troponin T (cTnT) and sensitive cardiac troponin I (s-cTnI) were also significantly higher in ischemic compared with nonischemic AHF patients (0.040 [0.010-0.306] MUg/L versus 0.018 [0.010-0.060] MUg/L [P<0.001]; 0.024 [0.008-0.106] MUg/L versus 0.016 [0.004-0.044 ] MUg/L [P=0.002]). The diagnostic accuracy of BNP, cTnT, and s-cTnI for the diagnosis of ischemic AHF, as quantified by the area under the receiver-operating characteristic curve, was low (0.58 [95% CI, 0.54-0.63], 0.61 [95% CI, 0.57-0.66], and 0.59 [95% CI,0.54 0.65], respectively). These findings were confirmed in the validation cohort. CONCLUSIONS: At presentation to the ED, patients with ischemic AHF exhibit more extensive hemodynamic cardiac stress and cardiomyocyte damage than patients with nonischemic AHF. However, the overlap is substantial, resulting in poor diagnostic accuracy. PMID- 21976471 TI - Enterococcal peritonitis in peritoneal dialysis patients: last name matters. PMID- 21976472 TI - Enterococcal peritonitis in peritoneal dialysis: the danger from within? PMID- 21976473 TI - Subcutaneous continuous erythropoietin receptor activator conversion provides practical advantages and potential convenience for peritoneal dialysis patients. PMID- 21976474 TI - Pharmacokinetics of intravenous teicoplanin in peritoneal dialysis patients with respiratory infections. PMID- 21976475 TI - Twice-daily icodextrin for ultrafiltration failure. PMID- 21976476 TI - Effects of combination therapy with peritoneal dialysis and hemodialysis on left ventricular hypertrophy. PMID- 21976477 TI - Ruptured abdominal aortic aneurysm as a cause of spontaneous hemoperitoneum in a patient on peritoneal dialysis. PMID- 21976478 TI - An important causative factor in peritoneal dialysis catheter removal: Salmonella Typhimurium. PMID- 21976479 TI - Streptococcus parasanguis peritonitis: report of a case and review of the literature. PMID- 21976480 TI - Two ancient bacterial-like PPP family phosphatases from Arabidopsis are highly conserved plant proteins that possess unique properties. AB - Protein phosphorylation, catalyzed by the opposing actions of protein kinases and phosphatases, is a cornerstone of cellular signaling and regulation. Since their discovery, protein phosphatases have emerged as highly regulated enzymes with specificity that rivals their counteracting kinase partners. However, despite years of focused characterization in mammalian and yeast systems, many protein phosphatases in plants remain poorly or incompletely characterized. Here, we describe a bioinformatic, biochemical, and cellular examination of an ancient, Bacterial-like subclass of the phosphoprotein phosphatase (PPP) family designated the Shewanella-like protein phosphatases (SLP phosphatases). The SLP phosphatase subcluster is highly conserved in all plants, mosses, and green algae, with members also found in select fungi, protists, and bacteria. As in other plant species, the nucleus-encoded Arabidopsis (Arabidopsis thaliana) SLP phosphatases (AtSLP1 and AtSLP2) lack genetic redundancy and phylogenetically cluster into two distinct groups that maintain different subcellular localizations, with SLP1 being chloroplastic and SLP2 being cytosolic. Using heterologously expressed and purified protein, the enzymatic properties of both AtSLP1 and AtSLP2 were examined, revealing unique metal cation preferences in addition to a complete insensitivity to the classic serine/threonine PPP protein phosphatase inhibitors okadaic acid and microcystin. The unique properties and high conservation of the plant SLP phosphatases, coupled to their exclusion from animals, red algae, cyanobacteria, archaea, and most bacteria, render understanding the function(s) of this new subclass of PPP family protein phosphatases of particular interest. PMID- 21976481 TI - Action of natural abscisic acid precursors and catabolites on abscisic acid receptor complexes. AB - The phytohormone abscisic acid (ABA) regulates stress responses and controls numerous aspects of plant growth and development. Biosynthetic precursors and catabolites of ABA have been shown to trigger ABA responses in physiological assays, but it is not clear whether these are intrinsically active or whether they are converted into ABA in planta. In this study, we analyzed the effect of ABA precursors, conjugates, and catabolites on hormone signaling in Arabidopsis (Arabidopsis thaliana). The compounds were also tested in vitro for their ability to regulate the phosphatase moiety of ABA receptor complexes consisting of the protein phosphatase 2C ABI2 and the coreceptors RCAR1/PYL9, RCAR3/PYL8, and RCAR11/PYR1. Using mutants defective in ABA biosynthesis, we show that the physiological activity associated with ABA precursors derives predominantly from their bioconversion to ABA. The ABA glucose ester conjugate, which is the most widespread storage form of ABA, showed weak ABA-like activity in germination assays and in triggering ABA signaling in protoplasts. The ABA conjugate and precursors showed negligible activity as a regulatory ligand of the ABI2/RCAR receptor complexes. The majority of ABA catabolites were inactive in our assays. To analyze the chemically unstable 8'- and 9'-hydroxylated ABA catabolites, we used stable tetralone derivatives of these compounds, which did trigger selective ABA responses. ABA synthetic analogs exhibited differential activity as regulatory ligands of different ABA receptor complexes in vitro. The data show that ABA precursors, catabolites, and conjugates have limited intrinsic bioactivity and that both natural and synthetic ABA-related compounds can be used to probe the structural requirements of ABA ligand-receptor interactions. PMID- 21976483 TI - The phosphorylation status of the chloroplast protein kinase STN7 of Arabidopsis affects its turnover. AB - The chloroplast serine-threonine protein kinase STN7 of Arabidopsis (Arabidopsis thaliana) is required for the phosphorylation of the light-harvesting system of photosystem II and for state transitions, a process that allows the photosynthetic machinery to balance the light excitation energy between photosystem II and photosystem I and thereby to optimize the photosynthetic yield. Because the STN7 protein kinase of Arabidopsis is known to be phosphorylated at four serine-threonine residues, we have changed these residues by site-directed mutagenesis to alanine (STN7-4A) or aspartic acid (STN7-4D) to assess the role of these phosphorylation events. The corresponding mutants were still able to phosphorylate the light-harvesting system of photosystem II and to perform state transitions. Moreover, we noticed a marked decrease in the level of the STN7 kinase in the wild-type strain under prolonged state 1 conditions that no longer occurs in the STN7-4D mutant. The results suggest a possible role of phosphorylation of the STN7 kinase in regulating its turnover. PMID- 21976482 TI - The presequence of Arabidopsis serine hydroxymethyltransferase SHM2 selectively prevents import into mesophyll mitochondria. AB - Serine hydroxymethyltransferases (SHMs) are important enzymes of cellular one carbon metabolism and are essential for the photorespiratory glycine-into-serine conversion in leaf mesophyll mitochondria. In Arabidopsis (Arabidopsis thaliana), SHM1 has been identified as the photorespiratory isozyme, but little is known about the very similar SHM2. Although the mitochondrial location of SHM2 can be predicted, some data suggest that this particular isozyme could be inactive or not targeted into mitochondria. We report that SHM2 is a functional mitochondrial SHM. In leaves, the presequence of SHM2 selectively hinders targeting of the enzyme into mesophyll mitochondria. For this reason, the enzyme is confined to the vascular tissue of wild-type Arabidopsis, likely the protoxylem and/or adjacent cells, where it occurs together with SHM1. The resulting exclusion of SHM2 from the photorespiratory environment of mesophyll mitochondria explains why this enzyme cannot substitute for SHM1 in photorespiratory metabolism. Unlike the individual shm1 and shm2 null mutants, which require CO(2)-enriched air to inhibit photorespiration (shm1) or do not show any visible impairment (shm2), double-null mutants cannot survive in CO(2)-enriched air. It seems that SHM1 and SHM2 operate in a redundant manner in one-carbon metabolism of nonphotorespiring cells with a high demand of one-carbon units; for example, during lignification of vascular cells. We hypothesize that yet unknown kinetic properties of SHM2 might render this enzyme unsuitable for the high-folate conditions of photorespiring mesophyll mitochondria. PMID- 21976484 TI - Expression of Arabidopsis SHORT INTERNODES/STYLISH family genes in auxin biosynthesis zones of aerial organs is dependent on a GCC box-like regulatory element. AB - Auxin/indole-3-acetic acid (IAA) biosynthesis in Arabidopsis (Arabidopsis thaliana) plays a major role in growth responses to developmental and genetic signals as well as to environmental stimuli. Knowledge of its regulation, however, remains rudimentary, and few proteins acting as transcriptional modulators of auxin biosynthesis have been identified. We have previously shown that alteration in the expression level of the SHORT INTERNODES/STYLISH (SHI/STY) family member STY1 affects IAA biosynthesis rates and IAA levels and that STY1 acts as a transcriptional activator of genes encoding auxin biosynthesis enzymes. Here, we have analyzed the upstream regulation of SHI/STY family members to gain further insight into transcriptional regulation of auxin biosynthesis. We attempted to modulate the normal expression pattern of STY1 by mutating a putative regulatory element, a GCC box, located in the proximal promoter region and conserved in most SHI/STY genes in Arabidopsis. Mutations in the GCC box abolish expression in aerial organs of the adult plant. We also show that induction of the transcriptional activator DORNROSCHEN-LIKE (DRNL) activates the transcription of STY1 and other SHI/STY family members and that this activation is dependent on a functional GCC box. Additionally, STY1 expression in the strong drnl-2 mutant or the drn drnl-1 puchi-1 triple mutant, carrying knockdown mutations in both DRNL and its close paralogue DRN as well as one of their closest homologs, PUCHI, was significantly reduced, suggesting that DRNL regulates STY1 during normal plant development and that several other genes might have redundant functions. PMID- 21976485 TI - Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. AB - Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene that impair the function of CFTR, an epithelial chloride channel required for proper function of the lung, pancreas, and other organs. Most patients with CF carry the F508del CFTR mutation, which causes defective CFTR protein folding and processing in the endoplasmic reticulum, resulting in minimal amounts of CFTR at the cell surface. One strategy to treat these patients is to correct the processing of F508del-CFTR with small molecules. Here we describe the in vitro pharmacology of VX-809, a CFTR corrector that was advanced into clinical development for the treatment of CF. In cultured human bronchial epithelial cells isolated from patients with CF homozygous for F508del, VX-809 improved F508del-CFTR processing in the endoplasmic reticulum and enhanced chloride secretion to approximately 14% of non-CF human bronchial epithelial cells (EC(50), 81 +/- 19 nM), a level associated with mild CF in patients with less disruptive CFTR mutations. F508del-CFTR corrected by VX-809 exhibited biochemical and functional characteristics similar to normal CFTR, including biochemical susceptibility to proteolysis, residence time in the plasma membrane, and single-channel open probability. VX-809 was more efficacious and selective for CFTR than previously reported CFTR correctors. VX-809 represents a class of CFTR corrector that specifically addresses the underlying processing defect in F508del-CFTR. PMID- 21976487 TI - Requirements for effective malaria control with homing endonuclease genes. AB - Malaria continues to impose a substantial burden on human health. We have previously proposed that biological approaches to control the mosquito vector of disease could be developed using homing endonuclease genes (HEGs), a class of selfish or parasitic gene that exists naturally in many microbes. Recent lab studies have demonstrated that HEGs can function in mosquitoes. We constructed and analyzed a model of mosquito population genetics and malaria epidemiology to determine how well HEGs need to function in order to have a significant effect on the burden of disease. Our model, combined with currently available data, indicates that populations of Anopheles gambiae could be eliminated by releasing 2-3 HEGs targeting female fertility genes, or a driving-Y chromosome that is transmitted to 75-96% of progeny. Combinations of fertility-targeting HEGs and Y drive may also be effective. It is possible to eliminate the disease without eliminating the vector, but the parameter space producing this outcome appears to be small. HEGs causing a quantitative reduction in adult survival can be more effective than those targeting female fertility, but the selection coefficients that need to be imposed are still large, unless many HEGs are to be released. Simulations show that HEG-based strategies can be effective over socially relevant time frames. Important limiting assumptions of the models are that there is only a single vector species, and we model a homogeneous population, not a landscape. Nevertheless, we conclude that HEG-based approaches could have a transformational effect on malaria control efforts. PMID- 21976486 TI - Priming of hypoxia-inducible factor by neuronal nitric oxide synthase is essential for adaptive responses to severe anemia. AB - Cells sense and respond to changes in oxygen concentration through gene regulatory processes that are fundamental to survival. Surprisingly, little is known about how anemia affects hypoxia signaling. Because nitric oxide synthases (NOSs) figure prominently in the cellular responses to acute hypoxia, we defined the effects of NOS deficiency in acute anemia. In contrast to endothelial NOS or inducible NOS deficiency, neuronal NOS (nNOS)(-/-) mice demonstrated increased mortality during anemia. Unlike wild-type (WT) animals, anemia did not increase cardiac output (CO) or reduce systemic vascular resistance (SVR) in nNOS(-/-) mice. At the cellular level, anemia increased expression of HIF-1alpha protein and HIF-responsive mRNA levels (EPO, VEGF, GLUT1, PDK1) in the brain of WT, but not nNOS(-/-) mice, despite comparable reductions in tissue PO(2). Paradoxically, nNOS(-/-) mice survived longer during hypoxia, retained the ability to regulate CO and SVR, and increased brain HIF-alpha protein levels and HIF-responsive mRNA transcripts. Real-time imaging of transgenic animals expressing a reporter HIF alpha(ODD)-luciferase chimeric protein confirmed that nNOS was essential for anemia-mediated increases in HIF-alpha protein stability in vivo. S-nitrosylation effects the functional interaction between HIF and pVHL. We found that anemia led to nNOS-dependent S-nitrosylation of pVHL in vivo and, of interest, led to decreased expression of GSNO reductase. These findings identify nNOS effects on the HIF/pVHL signaling pathway as critically important in the physiological responses to anemia in vivo and provide essential mechanistic insight into the differences between anemia and hypoxia. PMID- 21976489 TI - The role of dorsal striatal D2-like receptors in reversal learning: a reinforcement learning viewpoint. PMID- 21976488 TI - Implications for proteasome nuclear localization revealed by the structure of the nuclear proteasome tether protein Cut8. AB - Degradation of nuclear proteins by the 26S proteasome is essential for cell viability. In yeast, the nuclear envelope protein Cut8 mediates nuclear proteasomal sequestration by an uncharacterized mechanism. Here we describe structures of Schizosaccharomyces pombe Cut8, which shows that it contains a unique, modular fold composed of an extended N-terminal, lysine-rich segment that when ubiquitinated binds the proteasome, a dimer domain followed by a six-helix bundle connected to a flexible C tail. The Cut8 six-helix bundle shows structural similarity to 14-3-3 phosphoprotein-binding domains, and binding assays show that this domain is necessary and sufficient for liposome and cholesterol binding. Moreover, specific mutations in the 14-3-3 regions corresponding to putative cholesterol recognition/interaction amino acid consensus motifs abrogate cholesterol binding. In vivo studies confirmed that the 14-3-3 region is necessary for Cut8 membrane localization and that dimerization is critical for its function. Thus, the data reveal the Cut8 organization at the nuclear envelope. Reconstruction of Cut8 evolution suggests that it was present in the last common ancestor of extant eukaryotes and accordingly that nuclear proteasomal sequestration is an ancestral eukaryotic feature. The importance of Cut8 for cell viability and its absence in humans suggests it as a possible target for the development of specific chemotherapeutics against invasive fungal infections. PMID- 21976490 TI - Leukocyte common antigen-related phosphatase is a functional receptor for chondroitin sulfate proteoglycan axon growth inhibitors. AB - Chondroitin sulfate proteoglycans (CSPGs) are a family of extracellular matrix molecules with various functions in regulating tissue morphogenesis, cell division, and axon guidance. A number of CSPGs are highly upregulated by reactive glial scar tissues after injuries and form a strong barrier for axonal regeneration in the adult vertebrate CNS. Although CSPGs may negatively regulate axonal growth via binding and altering activity of other growth-regulating factors, the molecular mechanisms by which CSPGs restrict axonal elongation are not well understood. Here, we identified a novel receptor mechanism whereby CSPGs inhibit axonal growth via interactions with neuronal transmembrane leukocyte common antigen-related phosphatase (LAR). CSPGs bind LAR with high affinity in transfected COS-7 cells and coimmunoprecipitate with LAR expressed in various tissues including the brain and spinal cord. CSPG stimulation enhances activity of LAR phosphatase in vitro. Deletion of LAR in knock-out mice or blockade of LAR with sequence-selective peptides significantly overcomes neurite growth restrictions of CSPGs in neuronal cultures. Intracellularly, CSPG-LAR interaction mediates axonal growth inhibition of neurons partially via inactivating Akt and activating RhoA signals. Systemic treatments with LAR-targeting peptides in mice with thoracic spinal cord transection injuries induce significant axon growth of descending serotonergic fibers in the vicinity of the lesion and beyond in the caudal spinal cord and promote locomotor functional recovery. Identification of LAR as a novel CSPG functional receptor provides a therapeutic basis for enhancing axonal regeneration and functional recovery after CNS injuries in adult mammals. PMID- 21976491 TI - Human primary auditory cortex follows the shape of Heschl's gyrus. AB - The primary auditory cortex (PAC) is central to human auditory abilities, yet its location in the brain remains unclear. We measured the two largest tonotopic subfields of PAC (hA1 and hR) using high-resolution functional MRI at 7 T relative to the underlying anatomy of Heschl's gyrus (HG) in 10 individual human subjects. The data reveals a clear anatomical-functional relationship that, for the first time, indicates the location of PAC across the range of common morphological variants of HG (single gyri, partial duplications, and complete duplications). In 20/20 individual hemispheres, two primary mirror-symmetric tonotopic maps were clearly observed with gradients perpendicular to HG. PAC spanned both divisions of HG in cases of partial and complete duplications (11/20 hemispheres), not only the anterior division as commonly assumed. Specifically, the central union of the two primary maps (the hA1-R border) was consistently centered on the full Heschl's structure: on the gyral crown of single HGs and within the sulcal divide of duplicated HGs. The anatomical-functional variants of PAC appear to be part of a continuum, rather than distinct subtypes. These findings significantly revise HG as a marker for human PAC and suggest that tonotopic maps may have shaped HG during human evolution. Tonotopic mappings were based on only 16 min of fMRI data acquisition, so these methods can be used as an initial mapping step in future experiments designed to probe the function of specific auditory fields. PMID- 21976492 TI - alpha oscillations related to anticipatory attention follow temporal expectations. AB - Temporal expectations have been shown to enhance visual analysis of task-relevant events, especially when these are coupled with spatial expectations. Oscillatory brain activity, particularly in the alpha band, has been implicated in regulating excitability in visual areas as a function of anticipatory spatial attention. Here we asked whether temporal expectations derived from regular, rhythmic events can modulate ongoing oscillatory alpha-band activity, so that the changes in cortical excitability are focused over the time intervals at which target events are expected. The task we used involved making a perceptual discrimination about a small target stimulus that reappeared from "behind" a peripheral occluding band. Temporal expectations were manipulated by the regular, rhythmic versus irregular, arrhythmic approach of the stimulus toward the occluding band. Alpha band activity was measured during the occlusion period, in which no stimulus was presented, but target reappearance was anticipated in conditions of high versus low temporal expectation. Time-frequency analysis showed that the amplitude of alpha-desynchronization followed the time course of temporal expectations. Alpha desynchronization increased rhythmically, peaking just before the expected reappearance of target times. Analysis of the event-related potentials evoked by the subsequent target stimuli showed enhancement of processing at both visual and motor stages. Our findings support a role for oscillations in regulating cortical excitability and suggest a plausible mechanism for biasing perception and action by temporal expectations. PMID- 21976493 TI - Cortical excitation and inhibition following focal traumatic brain injury. AB - Cortical compression can be a significant problem in many types of brain injuries, such as brain trauma, localized brain edema, hematoma, focal cerebral ischemia, or brain tumors. Mechanical and cellular alterations can result in global changes in excitation and inhibition on the neuronal network level even in the absence of histologically significant cell injury, often manifesting clinically as seizures. Despite the importance and prevalence of this problem, however, the precise electrophysiological effects of brain injury have not been well characterized. In this study, the changes in electrophysiology were characterized following sustained cortical compression using large-scale, multielectrode measurement of multiunit activity in primary somatosensory cortex in a sensory-evoked, in vivo animal model. Immediately following the initiation of injury at a distal site, there was a period of suppression of the evoked response in the rat somatosensory cortex, followed by hyper-excitability that was accompanied by an increase in the spatial extent of cortical activation. Paired pulse tactile stimulation revealed a dramatic shift in the excitatory/inhibitory dynamics, suggesting a longer term hyperexcitability of the cortical circuit following the initial suppression that could be linked to the disruption of one or more inhibitory mechanisms of the thalamocortical circuit. Together, our results showed that the use of a sensory-evoked response provided a robust and repeatable functional marker of the evolution of the consequences of mild injury, serving as an important step toward in vivo quantification of alterations in excitation and inhibition in the cortex in the setting of traumatic brain injury. PMID- 21976494 TI - Chloride ions in the pore of glycine and GABA channels shape the time course and voltage dependence of agonist currents. AB - In the vertebrate CNS, fast synaptic inhibition is mediated by GABA and glycine receptors. We recently reported that the time course of these synaptic currents is slower when intracellular chloride is high. Here we extend these findings to measure the effects of both extracellular and intracellular chloride on the deactivation of glycine and GABA currents at both negative and positive holding potentials. Currents were elicited by fast agonist application to outside-out patches from HEK-293 cells expressing rat glycine or GABA receptors. The slowing effect of high extracellular chloride on current decay was detectable only in low intracellular chloride (4 mm). Our main finding is that glycine and GABA receptors "sense" chloride concentrations because of interactions between the M2 pore-lining domain and the permeating ions. This hypothesis is supported by the observation that the sensitivity of channel gating to intracellular chloride is abolished if the channel is engineered to become cation selective or if positive charges in the external pore vestibule are eliminated by mutagenesis. The appropriate interaction between permeating ions and channel pore is also necessary to maintain the channel voltage sensitivity of gating, which prolongs current decay at depolarized potentials. Voltage dependence is abolished by the same mutations that suppress the effect of intracellular chloride and also by replacing chloride with another permeant ion, thiocyanate. These observations suggest that permeant chloride affects gating by a foot-in-the-door effect, binding to a channel site with asymmetrical access from the intracellular and extracellular sides of the membrane. PMID- 21976495 TI - Uncontrollable, but not controllable, stress desensitizes 5-HT1A receptors in the dorsal raphe nucleus. AB - Uncontrollable stressors produce behavioral changes that do not occur if the organism can exercise behavioral control over the stressor. Previous studies suggest that the behavioral consequences of uncontrollable stress depend on hypersensitivity of serotonergic neurons in the dorsal raphe nucleus (DRN), but the mechanisms involved have not been determined. We used ex vivo single-unit recording in rats to test the hypothesis that the effects of uncontrollable stress are produced by desensitization of DRN 5-HT(1A) autoreceptors. These studies revealed that uncontrollable, but not controllable, tail shock impaired 5 HT(1A) receptor-mediated inhibition of DRN neuronal firing. Moreover, this effect was observed only at time points when the behavioral effects of uncontrollable stress are present. Furthermore, temporary inactivation of the medial prefrontal cortex with the GABA(A) receptor agonist muscimol, which eliminates the protective effects of control on behavior, led even controllable stress to now produce functional desensitization of DRN 5-HT(1A) receptors. Additionally, behavioral immunization, an experience with controllable stress before uncontrollable stress that prevents the behavioral outcomes of uncontrollable stress, also blocked functional desensitization of DRN 5-HT(1A) receptors by uncontrollable stress. Last, Western blot analysis revealed that uncontrollable stress leads to desensitization rather than downregulation of DRN 5-HT(1A) receptors. Thus, treatments that prevent controllable stress from being protective led to desensitization of 5-HT(1A) receptors, whereas treatments that block the behavioral effects of uncontrollable stress also blocked 5-HT(1A) receptor desensitization. These data suggest that uncontrollable stressors produce a desensitization of DRN 5-HT(1A) autoreceptors and that this desensitization is responsible for the behavioral consequences of uncontrollable stress. PMID- 21976496 TI - GABAergic precursor transplantation into the prefrontal cortex prevents phencyclidine-induced cognitive deficits. AB - Phencyclidine (PCP) is a noncompetitive NMDA receptor antagonist, and it induces schizophreniform cognitive deficits in healthy humans and similar cognitive deficits in rodents. Although the PCP-induced cognitive deficits appear to be accompanied and possibly caused by dysfunction of GABAergic inhibitory interneurons in the prefrontal cortex (PFC), the potential benefit(s) of GABAergic interneuron manipulations on PCP-induced cognitive deficits remains unexplored. In this study we show that when embryonic medial ganglionic eminence (MGE) cells, many of which differentiate into cortical GABAergic interneurons in situ, were grafted into the medial PFC (mPFC) of neonatal mice, they differentiated into a specific class of GABAergic interneurons and became functionally integrated into the host neuronal circuitry in adults. Prior MGE cell transplantation into the mPFC significantly prevented the induction of cognitive and sensory-motor gating deficits by PCP. The preventive effects were not reproduced by either transplantation of cortical projection neuron precursors into the mPFC or transplantation of MGE cells into the occipital cortex. The preventive effects of MGE cell transplantation into the mPFC were accompanied by activation of callosal projection neurons in the mPFC. These findings suggest that increasing GABAergic interneuron precursors in the PFC may contribute to the development of a cell-based approach as a novel means of modulating the PFC neuronal circuitry and preventing schizophreniform cognitive deficits. PMID- 21976497 TI - Homotypic regulation of neuronal morphology and connectivity in the mouse retina. AB - The establishment of neuronal circuitry during development relies upon the action of cell-intrinsic mechanisms that specify neuronal form as well as plastic processes that require the transmission of neural activity between afferents and their targets. Here, we examine the role of interactions between neighboring like type cells within the mouse retina upon neuronal differentiation and circuit formation. Two different genetically modified mouse models were used to modulate the density of homotypic neighbors, the Type 7 cone bipolar cells, without affecting the density of their afferents, the cone photoreceptors. We demonstrate a corresponding plasticity in dendritic field area when the density of Type 7 cone bipolar cells is elevated or reduced. In accord with this variation in dendritic field area across an invariant population of afferents, individual Type 7 cone bipolar cells are also shown to modulate the number of cone pedicles contacted without varying the number of contacts at each cone pedicle. Analysis of developing Type 7 cone bipolar cells reveals that the dendritic tiling present in maturity is achieved secondarily, after an initial stage of dendritic overlap, when the dendritic terminals are stratified at the level of the cone pedicles but are not localized to them. These results demonstrate a conspicuous developmental plasticity in neural circuit formation independent of neural activity, requiring homotypic interactions between neighboring cells that ultimately regulate connectivity within the retina. PMID- 21976498 TI - Alk is a transcriptional target of LMO4 and ERalpha that promotes cocaine sensitization and reward. AB - Previously, we showed that the mouse LIM-domain only 4 (Lmo4) gene, which encodes a protein containing two zinc-finger LIM domains that interact with various DNA binding transcription factors, attenuates behavioral sensitivity to repeated cocaine administration. Here we show that transcription of anaplastic lymphoma kinase (Alk) is repressed by LMO4 in the striatum and that Alk promotes the development of cocaine sensitization and conditioned place preference, a measure of cocaine reward. Since LMO4 is known to interact with estrogen receptor alpha (ERalpha) at the promoters of target genes, we investigated whether Alk expression might be controlled by a similar mechanism. We found that LMO4 and ERalpha are associated with the Alk promoter by chromatin immunoprecipitation and that Alk is an estrogen-responsive gene in the striatum. Moreover, we show that ERalpha knock-out mice exhibit enhanced cocaine sensitization and conditioned place preference and an increase in Alk expression in the nucleus accumbens. These data define a novel regulatory network involved in behavioral responses to cocaine. Interestingly, sex differences in several behavioral responses to cocaine in humans and rodents have been described, and estrogen is thought to mediate some of these differences. Our data suggest that estrogen regulation of Alk may be one mechanism responsible for sexually dimorphic responses to cocaine. PMID- 21976499 TI - Multiple arithmetic operations in a single neuron: the recruitment of adaptation processes in the cricket auditory pathway depends on sensory context. AB - Sensory pathways process behaviorally relevant signals in various contexts and therefore have to adapt to differing background conditions. Depending on changes in signal statistics, this adjustment might be a combination of two fundamental computational operations: subtractive adaptation shifting a neuron's threshold and divisive gain control scaling its sensitivity. The cricket auditory system has to deal with highly stereotyped conspecific songs at low carrier frequencies, and likely much more variable predator signals at high frequencies. We proposed that due to the differences between the two signal classes, the operation that is implemented by adaptation depends on the carrier frequency. We aimed to identify the biophysical basis underlying the basic computational operations of subtraction and division. We performed in vivo intracellular and extracellular recordings in a first-order auditory interneuron (AN2) that is active in both mate recognition and predator avoidance. We demonstrated subtractive shifts at the carrier frequency of conspecific songs and division at the predator-like carrier frequency. Combined application of current injection and acoustic stimuli for each cell allowed us to demonstrate the subtractive effect of cell-intrinsic adaptation currents. Pharmacological manipulation enabled us to demonstrate that presynaptic inhibition is most likely the source of divisive gain control. We showed that adjustment to the sensory context can depend on the class of signals that are relevant to the animal. We further revealed that presynaptic inhibition is a simple mechanism for divisive operations. Unlike other proposed mechanisms, it is widely available in the sensory periphery of both vertebrates and invertebrates. PMID- 21976500 TI - Intraamygdala infusion of fibroblast growth factor 2 enhances extinction and reduces renewal and reinstatement in adult rats. AB - Systemic fibroblast growth factor 2 (FGF2) has been shown to enhance extinction of conditioned fear and attenuate subsequent relapse in developing rats. However, it is not clear whether FGF2 has the same effect in adult rats, and furthermore, the neuroanatomical locus of the effect of FGF2 on extinction is unknown. These experiments examined the effect of 200 ng of FGF2, infused bilaterally into the basolateral complex of the amygdala (BLA), on the extinction of conditioned fear in adult rats. Experiment 1 confirmed that intra-BLA FGF2 significantly enhances extinction recall in adult rats, and extinction training is necessary for this effect to occur (FGF2 did not reduce conditioned freezing in the absence of extinction training). In Experiments 2 and 3, vehicle-treated rats were given four times the amount of extinction training as FGF2-treated rats to equate the strength of extinction between groups. In Experiment 2, rats were tested in both the extinction training context and the conditioning context to examine the effect of FGF2 on renewal of fear. In Experiment 3, the FGF2-treated rats and one half of the vehicle-treated rats received a single unsignaled shock before test to examine the effect of FGF2 on reinstatement of fear. In both procedures, FGF2 administered immediately after extinction training significantly reduced relapse at test. These results support a growing body of evidence that FGF2 may be a potentially useful pharmacological adjunct to exposure-based therapies for anxiety disorders. PMID- 21976501 TI - Regulation of neuronal M-channel gating in an isoform-specific manner: functional interplay between calmodulin and syntaxin 1A. AB - Whereas neuronal M-type K(+) channels composed of KCNQ2 and KCNQ3 subunits regulate firing properties of neurons, presynaptic KCNQ2 subunits were demonstrated to regulate neurotransmitter release by directly influencing presynaptic function. Two interaction partners of M-channels, syntaxin 1A and calmodulin, are known to act presynaptically, syntaxin serving as a major protein component of the membrane fusion machinery and calmodulin serving as regulator of several processes related to neurotransmitter release. Notably, both partners specifically modulate KCNQ2 but not KCNQ3 subunits, suggesting selective presynaptic targeting to directly regulate exocytosis without interference in neuronal firing properties. Here, having first demonstrated in Xenopus oocytes, using analysis of single-channel biophysics, that both modulators downregulate the open probability of KCNQ2 but not KCNQ3 homomers, we sought to resolve the channel structural determinants that confer the isoform-specific gating downregulation and to get insights into the molecular events underlying this mechanism. We show, using optical, biochemical, electrophysiological, and molecular biology analyses, the existence of constitutive interactions between the N and C termini in homomeric KCNQ2 and KCNQ3 channels in living cells. Furthermore, rearrangement in the relative orientation of the KCNQ2 termini that accompanies reduction in single-channel open probability is induced by both regulators, strongly suggesting that closer N-C termini proximity underlies gating downregulation. Different structural determinants, identified at the N and C termini of KCNQ3, prevent the effects by syntaxin 1A and calmodulin, respectively. Moreover, we show that the syntaxin 1A and calmodulin effects can be additive or blocked at different concentration ranges of calmodulin, bearing physiological significance with regard to presynaptic exocytosis. PMID- 21976502 TI - Stress and glucocorticoids impair memory retrieval via beta2-adrenergic, Gi/o coupled suppression of cAMP signaling. AB - Acute stress impairs the retrieval of hippocampus-dependent memory, and this effect is mimicked by exogenous administration of stress-responsive glucocorticoid hormones. It has been proposed that glucocorticoids affect memory by promoting the release and/or blocking the reuptake of norepinephrine (NE), a stress-responsive neurotransmitter. It has also been proposed that this enhanced NE signaling impairs memory retrieval by stimulating beta(1)-adrenergic receptors and elevating levels of cAMP. In contrast, other evidence indicates that NE, beta(1), and cAMP signaling is transiently required for the retrieval of hippocampus-dependent memory. To resolve this discrepancy, wild-type rats and mice with and without gene-targeted mutations were stressed or treated with glucocorticoids and/or adrenergic receptor drugs before testing memory for inhibitory avoidance or fear conditioning. Here we report that glucocorticoids do not require NE to impair retrieval. However, stress- and glucocorticoid-induced impairments of retrieval depend on the activation of beta(2) (but not beta(1)) adrenergic receptors. Offering an explanation for the opposing functions of these two receptors, the impairing effects of stress, glucocorticoids and beta(2) agonists on retrieval are blocked by pertussis toxin, which inactivates signaling by G(i/o)-coupled receptors. In hippocampal slices, beta(2) signaling decreases cAMP levels and greatly reduces the increase in cAMP mediated by beta(1) signaling. Finally, augmenting cAMP signaling in the hippocampus prevents the impairment of retrieval by systemic beta(2) agonists or glucocorticoids. These results demonstrate that the beta(2) receptor can be a critical effector of acute stress, and that beta(1) and beta(2) receptors can have quite distinct roles in CNS signaling and cognition. PMID- 21976503 TI - Levels of BDNF impact oligodendrocyte lineage cells following a cuprizone lesion. AB - Previous work in culture has shown that basal forebrain (BF) oligodendrocyte (OLG) lineage cells respond to BDNF by increasing DNA synthesis and differentiation. Further, in the BF in vivo, reduced levels of BDNF as seen in BDNF(+/-) mice result in reduced numbers of NG2+ cells and deficits in myelin proteins throughout development and in the adult, suggesting that BDNF impacts the proliferating population of OLGs as well as differentiation in vivo. In this study, to investigate the roles BDNF may play in the repair of a demyelinating lesion, the cuprizone model was used and the corpus callosum was examined. BDNF protein levels were reduced after cuprizone treatment, suggesting that the demyelinating lesion itself elicits a decrease in BDNF. To analyze the effects of a further reduction of BDNF on OLG lineage cells following cuprizone, BDNF(+/-) mice were evaluated. These mice exhibited a blunted increase in the NG2 response at 4 and 5 weeks of cuprizone treatment. In addition, BDNF(+/-) mice exhibited decreased levels of myelin proteins during the demyelination and remyelination processes with no change in the total number of OLGs. These effects appear to be relatively specific to OLG lineage cells as comparable changes in CD11b+ microglia, GFAP+ astrocytes, and SMI32+ injured axons were not observed. These data indicate that BDNF may play a role following a demyelinating lesion by regulating the numbers of progenitors and the abilities of demyelinating and differentiating cells to express myelin proteins. PMID- 21976504 TI - MicroRNA as repressors of stress-induced anxiety: the case of amygdalar miR-34. AB - The etiology and pathophysiology of anxiety and mood disorders is linked to inappropriate regulation of the central stress response. To determine whether microRNAs have a functional role in the regulation of the stress response, we inactivated microRNA processing by a lentiviral-induced local ablation of the Dicer gene in the central amygdala (CeA) of adult mice. CeA Dicer ablation induced a robust increase in anxiety-like behavior, whereas manipulated neurons survive and appear to exhibit normal gross morphology in the time period examined. We also observed that acute stress in wild-type mice induced a differential expression profile of microRNAs in the amygdala. Bioinformatic analysis identified putative gene targets for these stress-responsive microRNAs, some of which are known to be associated with stress. One of the prominent stress induced microRNAs found in this screen, miR-34c, was further confirmed to be upregulated after acute and chronic stressful challenge and downregulated in Dicer ablated cells. Lentivirally mediated overexpression of miR34c specifically within the adult CeA induced anxiolytic behavior after challenge. Of particular interest, one of the miR-34c targets is the stress-related corticotropin releasing factor receptor type 1 (CRFR1) mRNA, regulated via a single evolutionary conserved seed complementary site on its 3' UTR. Additional in vitro studies demonstrated that miR-34c reduces the responsiveness of cells to CRF in neuronal cells endogenously expressing CRFR1. Our results suggest a physiological role for microRNAs in regulating the central stress response and position them as potential targets for treatment of stress-related disorders. PMID- 21976505 TI - Cortical projections of functionally identified thalamic trigeminovascular neurons: implications for migraine headache and its associated symptoms. AB - This study identifies massive axonal arbors of trigeminovascular (dura-sensitive) thalamic neurons in multiple cortical areas and proposes a novel framework for conceptualizing migraine headache and its associated symptoms. Individual dura sensitive neurons identified and characterized electrophysiologically in first order and higher-order relay thalamic nuclei were juxtacellularly filled with an anterograde tracer that labeled their cell bodies and processes. First-order neurons located in the ventral posteromedial nucleus projected mainly to trigeminal areas of primary (S1) as well as secondary (S2) somatosensory and insular cortices. Higher-order neurons located in the posterior (Po), lateral posterior (LP), and lateral dorsal (LD) nuclei projected to trigeminal and extra trigeminal areas of S1 and S2, as well as parietal association, retrosplenial, auditory, ectorhinal, motor, and visual cortices. Axonal arbors spread at various densities across most layers of the different cortical areas. Such parallel network of thalamocortical projections may play different roles in the transmission of nociceptive signals from the meninges to the cortex. The findings that individual dura-sensitive Po, LP, and LD neurons project to many functionally distinct and anatomically remote cortical areas extend current thinking on projection patterns of high-order thalamic neurons and position them to relay nociceptive information directly rather than indirectly from one cortical area to another. Such extensive input to diverse cortical areas that are involved in regulation of affect, motor function, visual and auditory perception, spatial orientation, memory retrieval, and olfaction may explain some of the common disturbances in neurological functions during migraine. PMID- 21976506 TI - KIBRA polymorphism is related to enhanced memory and elevated hippocampal processing. AB - Several studies have linked the KIBRA rs17070145 T polymorphism to superior episodic memory in healthy humans. One study investigated the effect of KIBRA on brain activation patterns (Papassotiropoulos et al., 2006) and observed increased hippocampal activation in noncarriers of the T allele during retrieval. Noncarriers were interpreted to need more hippocampal activation to reach the same performance level as T carriers. Using large behavioral (N = 2230) and fMRI (N = 83) samples, we replicated the KIBRA effect on episodic memory performance, but found increased hippocampal activation in T carriers during episodic retrieval. There was no evidence of compensatory brain activation in noncarriers within the hippocampal region. In the main fMRI sample, T carriers performed better than noncarriers during scanning but, importantly, the difference in hippocampus activation remained after post hoc matching according to performance, sex, and age (N = 64). These findings link enhanced memory performance in KIBRA T allele carriers to elevated hippocampal functioning, rather than to neural compensation in noncarriers. PMID- 21976507 TI - Altered neocortical rhythmic activity states in Fmr1 KO mice are due to enhanced mGluR5 signaling and involve changes in excitatory circuitry. AB - Despite the pronounced neurological deficits associated with mental retardation and autism, the degree to which neocortical circuit function is altered remains unknown. Here, we study changes in neocortical network function in the form of persistent activity states in the mouse model of fragile X syndrome--the Fmr1 knock-out (KO). Persistent activity states, or UP states, in the neocortex underlie the slow oscillation which occurs predominantly during slow-wave sleep, but may also play a role during awake states. We show that spontaneously occurring UP states in the primary somatosensory cortex are 38-67% longer in Fmr1 KO slices. In vivo, UP states reoccur with a clear rhythmic component consistent with that of the slow oscillation and are similarly longer in the Fmr1 KO. Changes in neocortical excitatory circuitry likely play the major role in this alteration as supported by three findings: (1) longer UP states occur in slices of isolated neocortex, (2) pharmacologically isolated excitatory circuits in Fmr1 KO neocortical slices display prolonged bursting states, and (3) selective deletion of Fmr1 in cortical excitatory neurons is sufficient to cause prolonged UP states whereas deletion in inhibitory neurons has no effect. Excess signaling mediated by the group 1 glutamate metabotropic receptor, mGluR5, contributes to the longer UP states. Genetic reduction or pharmacological blockade of mGluR5 rescues the prolonged UP state phenotype. Our results reveal an alteration in network function in a mouse model of intellectual disability and autism which may impact both slow-wave sleep and information processing during waking states. PMID- 21976508 TI - Large identified pyramidal cells in macaque motor and premotor cortex exhibit "thin spikes": implications for cell type classification. AB - Recent studies have suggested that extracellular recordings of putative cortical interneurons have briefer spikes than those of pyramidal neurons, providing a means of identifying cortical cell types in recordings from awake monkeys. To test this, we investigated the spike duration of antidromically identified pyramidal tract neurons (PTNs) recorded from primary motor (M1) or ventral premotor cortex (area F5) in 4 awake macaque monkeys. M1 antidromic latencies (ADLs) were skewed toward short ADLs (151 PTNs; 0.5-5.5 ms, median 1.1 ms) and significantly different from that of F5 ADLs (54 PTNs; 1.0-6.9 ms, median 2.6 ms). The duration of PTN spikes, recorded with a high-pass filter of 300 Hz and measured from the negative trough to the positive peak of the spike waveform, ranged from 0.15 to 0.71 ms. Importantly, we found a positive linear correlation between ADL and spike duration in both M1 (R(2) = 0.40, p < 0.001) and F5 (R(2) = 0.57, p < 0.001). Thus PTNs with the shortest ADL (fastest axons) had the briefest spikes, and since PTN soma size is correlated with axon size and conduction velocity, it is likely that the largest pyramidal neurons (Betz cells in M1) have spikes with short durations (0.15-0.45 ms), which overlap heavily with those reported for putative interneurons in previous studies in non primates. In summary, one class of physiologically identified cortical pyramidal neuron exhibits a wide variety of spike durations and the results suggest that spike duration alone may not be a reliable indicator of cell type. PMID- 21976509 TI - MU-suppression during action observation and execution correlates with BOLD in dorsal premotor, inferior parietal, and SI cortices. AB - The discovery of mirror neurons in the monkey, that fire during both the execution and the observation of the same action, sparked great interest in studying the human equivalent. For over a decade, both functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) have been used to quantify activity in the human mirror neuron system (MNS)-yet, little is still known about how fMRI and EEG measures of the MNS relate to each other. To test the frequent assumption that regions of the MNS as evidenced by fMRI are the origin of the suppression of the EEG MU-rhythm during both action execution and observation, we recorded EEG and BOLD-fMRI signals simultaneously while participants observed and executed actions. We found that the suppression of the MU-rhythm in EEG covaried with BOLD activity in typical MNS regions, inferior parietal lobe (IPL), dorsal premotor (dPM) and primary somatosensory cortex (BA2), during both action observation and execution. In contrast, in BA44, only nonoverlapping voxels correlated with MU-suppression during observation and execution. These findings provide direct support for the notion that MU suppression is a valid indicator of MNS activity in BA2, IPL, and dPM, but argues against the idea that mirror neurons in BA44 are the prime source of MU suppression. These results shed light on the neural basis of MU-suppression and provide a basis for integrating more closely the flourishing but often separate literatures on the MNS using fMRI and EEG. PMID- 21976510 TI - Piccolo regulates the dynamic assembly of presynaptic F-actin. AB - Filamentous (F)-actin is a known regulator of the synaptic vesicle (SV) cycle, with roles in SV mobilization, fusion, and endocytosis. However, the molecular pathways that regulate its dynamic assembly within presynaptic boutons remain unclear. In this study, we have used shRNA-mediated knockdown to demonstrate that Piccolo, a multidomain protein of the active zone cytomatrix, is a key regulator of presynaptic F-actin assembly. Boutons lacking Piccolo exhibit enhanced activity-dependent Synapsin1a dispersion and SV exocytosis, and reduced F-actin polymerization and CaMKII recruitment. These phenotypes are rescued by stabilizing F-actin filaments and mimicked by knocking down Profilin2, another regulator of presynaptic F-actin assembly. Importantly, we find that mice with a targeted deletion of exon 14 from the Pclo gene, reported to lack >95% of Piccolo, continue to express multiple Piccolo isoforms. Furthermore, neurons cultured from these mice exhibit no defects in presynaptic F-actin assembly due to the expression of these isoforms at presynaptic boutons. These data reveal that Piccolo regulates neurotransmitter release by facilitating activity dependent F-actin assembly and the dynamic recruitment of key signaling molecules into presynaptic boutons, and highlight the need for new genetic models with which to study Piccolo loss of function. PMID- 21976511 TI - NBCe1 mediates the acute stimulation of astrocytic glycolysis by extracellular K+. AB - Excitatory synaptic transmission stimulates brain tissue glycolysis. This phenomenon is the signal detected in FDG-PET imaging and, through enhanced lactate production, is also thought to contribute to the fMRI signal. Using a method based on Forster resonance energy transfer in mouse astrocytes, we have recently observed that a small rise in extracellular K(+) can stimulate glycolysis by >300% within seconds. The K(+) response was blocked by ouabain, but intracellular engagement of the Na(+)/K(+) ATPase pump with Na(+) was ineffective, suggesting that the canonical feedback regulatory pathway involving the Na(+) pump and ATP depletion is only permissive and that a second mechanism is involved. Because of their predominant K(+) permeability and high expression of the electrogenic Na(+)/HCO(3)(-) cotransporter NBCe1, astrocytes respond to a rise in extracellular K(+) with plasma membrane depolarization and intracellular alkalinization. In the present article, we show that a fast glycolytic response can be elicited independently of K(+) by plasma membrane depolarization or by intracellular alkalinization. The glycolytic response to K(+) was absent in astrocytes from NBCe1 null mice (Slc4a4) and was blocked by functional or pharmacological inhibition of the NBCe1. Hippocampal neurons acquired K(+) sensitive glycolysis upon heterologous NBCe1 expression. The phenomenon could also be reconstituted in HEK293 cells by coexpression of the NBCe1 and a constitutively open K(+) channel. We conclude that the NBCe1 is a key element in a feedforward mechanism linking excitatory synaptic transmission to fast modulation of glycolysis in astrocytes. PMID- 21976512 TI - The effect of noise correlations in populations of diversely tuned neurons. AB - The amount of information encoded by networks of neurons critically depends on the correlation structure of their activity. Neurons with similar stimulus preferences tend to have higher noise correlations than others. In homogeneous populations of neurons, this limited range correlation structure is highly detrimental to the accuracy of a population code. Therefore, reduced spike count correlations under attention, after adaptation, or after learning have been interpreted as evidence for a more efficient population code. Here, we analyze the role of limited range correlations in more realistic, heterogeneous population models. We use Fisher information and maximum-likelihood decoding to show that reduced correlations do not necessarily improve encoding accuracy. In fact, in populations with more than a few hundred neurons, increasing the level of limited range correlations can substantially improve encoding accuracy. We found that this improvement results from a decrease in noise entropy that is associated with increasing correlations if the marginal distributions are unchanged. Surprisingly, for constant noise entropy and in the limit of large populations, the encoding accuracy is independent of both structure and magnitude of noise correlations. PMID- 21976513 TI - Caudate dopamine D1 receptor density is associated with individual differences in frontoparietal connectivity during working memory. AB - We assess the relationship of age-related losses in striatal D1 receptor densities to age-related reductions in functional connectivity between spatially distinct cortical regions in healthy human participants. Previous neuroimaging studies have reported age-related differences in functional connectivity of the frontoparietal working memory network and the default mode network during task performance. We used functional magnetic resonance imaging and seed-based connectivity (right dorsolateral and medial prefrontal cortex) to extend these findings: Anterior-posterior connectivity of both these functional networks was reduced in older (65-75 years, n = 18) compared with younger (20-30 years, n = 19) adults, whereas bilateral connectivity in prefrontal cortex was increased in older adults. Positron emission tomography with the D1 receptor ligand [(11)C]SCH23390 was used to assess caudate D1 receptor density in the same sample. Older adults showed significantly reduced caudate D1 receptor density compared to the younger adults. Of key interest, partial correlations showed that individual differences in caudate D1 receptor density were positively associated with individual differences in dorsolateral prefrontal connectivity to right parietal cortex (BA40) and negatively with medial prefrontal connectivity to right parietal cortex (BA40 and postcentral gyrus), after controlling for age. We found no correlation of caudate D1 receptor density with anterior-posterior coupling within the default mode network or with bilateral frontal connectivity. These results are consistent with animal work that has identified a role for caudate D1 receptors in mediating information transfer between prefrontal areas and parietal cortex. PMID- 21976514 TI - Rapid loss of dendritic HCN channel expression in hippocampal pyramidal neurons following status epilepticus. AB - Epilepsy is associated with loss of expression and function of hyperpolarization activated, cyclic nucleotide-gated (HCN) ion channels. Previously, we showed that loss of HCN channel-mediated current (I(h)) occurred in the dendrites of CA1 hippocampal pyramidal neurons after pilocarpine-induced status epilepticus (SE), accompanied by loss of HCN1 channel protein expression. However, the precise onset and mechanistic basis of HCN1 channel loss post-SE was unclear, particularly whether it preceded the onset of spontaneous recurrent seizures and could contribute to epileptogenesis or development of the epileptic state. Here, we found that loss of I(h) and HCN1 channel expression began within an hour after SE and involved sequential processes of dendritic HCN1 channel internalization, delayed loss of protein expression, and later downregulation of mRNA expression. We also found that an in vitro SE model reproduced the rapid loss of dendritic I(h), demonstrating that this phenomenon was not specific to in vivo SE. Together, these results show that HCN1 channelopathy begins rapidly and persists after SE, involves both transcriptional and nontranscriptional mechanisms, and may be an early contributor to epileptogenesis. PMID- 21976515 TI - Alterations of molecular and behavioral responses to cocaine by selective inhibition of Elk-1 phosphorylation. AB - Activation of the extracellular signal-regulated kinase (ERK) signaling pathway in the striatum is crucial for molecular adaptations and long-term behavioral alterations induced by cocaine. In response to cocaine, ERK controls the phosphorylation levels of both mitogen and stress-activated protein kinase 1 (MSK 1), a nuclear kinase involved in histone H3 (Ser10) and cAMP response element binding protein phosphorylation, and Elk-1, a transcription factor involved in serum response element (SRE)-driven gene regulations. We recently characterized the phenotype of msk-1 knock-out mice in response to cocaine. Herein, we wanted to address the role of Elk-1 phosphorylation in cocaine-induced molecular, morphological, and behavioral responses. We used a cell-penetrating peptide, named TAT-DEF-Elk-1 (TDE), which corresponds to the DEF docking domain of Elk-1 toward ERK and inhibits Elk-1 phosphorylation induced by ERKs without modifying ERK or MSK-1 in vitro. The peptide was injected in vivo before cocaine administration in mice. Immunocytochemical, molecular, morphological, and behavioral studies were performed. The TDE inhibited Elk-1 and H3 (Ser10) phosphorylation induced by cocaine, sparing ERK and MSK-1 activation. Consequently, TDE altered cocaine-induced regulation of genes bearing SRE site(s) in their promoters, including c-fos, zif268, DeltaFosB, and arc/arg3.1 (activity regulated cytoskeleton-associated protein). In a chronic cocaine administration paradigm, TDE reversed cocaine-induced increase in dendritic spine density. Finally, the TDE delayed the establishment of cocaine-induced psychomotor sensitization and conditioned-place preference. We conclude that Elk-1 phosphorylation downstream from ERK is a key molecular event involved in long term neuronal and behavioral adaptations to cocaine. PMID- 21976516 TI - A specific brain structural basis for individual differences in reality monitoring. AB - Much recent interest has centered on understanding the relationship between brain structure variability and individual differences in cognition, but there has been little progress in identifying specific neuroanatomical bases of such individual differences. One cognitive ability that exhibits considerable variability in the healthy population is reality monitoring; the cognitive processes used to introspectively judge whether a memory came from an internal or external source (e.g., whether an event was imagined or actually occurred). Neuroimaging research has implicated the medial anterior prefrontal cortex (PFC) in reality monitoring, and here we sought to determine whether morphological variability in a specific anteromedial PFC brain structure, the paracingulate sulcus (PCS), might underlie performance. Fifty-three healthy volunteers were selected on the basis of MRI scans and classified into four groups according to presence or absence of the PCS in their left or right hemisphere. The group with absence of the PCS in both hemispheres showed significantly reduced reality monitoring performance and ability to introspect metacognitively about their performance when compared with other participants. Consistent with the prediction that sulcal absence might mean greater volume in the surrounding frontal gyri, voxel-based morphometry revealed a significant negative correlation between anterior PFC gray matter and reality monitoring performance. The findings provide evidence that individual differences in introspective abilities like reality monitoring may be associated with specific structural variability in the PFC. PMID- 21976517 TI - Cell-autonomous and non-cell-autonomous neuroprotective functions of RORalpha in neurons and astrocytes during hypoxia. AB - There is increasing evidence to suggest that the neuronal response to hypoxia is regulated through their interactions with astrocytes. However, the hypoxia induced molecular mechanisms within astrocytes which influence neuronal death have yet to be characterized. In this study, we investigated the roles of the nuclear receptor RORalpha (retinoid-related orphan receptor-alpha) respectively in neurons and astrocytes during hypoxia using cultures and cocultures of neurons and astrocytes obtained from RORalpha-deficient mice. We found that loss of RORalpha function in neuronal cultures increases neuronal death after hypoxia, suggesting a cell-autonomous neuroprotective effect of RORalpha. Moreover, wild type neurons cocultured with RORalpha-deficient astrocytes are characterized by a higher death rate after hypoxia than neurons cocultured with wild-type astrocytes, suggesting that RORalpha also has a non-cell-autonomous action. By using cocultures of neurons and astrocytes of different genotypes, we showed that this neuroprotective effect of RORalpha in astrocytes is additive to its effect in neurons, and is mediated in part by cell-to-cell interactions between neurons and astrocytes. We also found that RORalpha is upregulated by hypoxia in both neurons and astrocytes. Furthermore, our data showed that RORalpha does not alter oxidative mechanisms during hypoxia but regulates hypoxic inducible factor 1alpha (HIF-1alpha) expression, a major regulator of hypoxia sensing, in a cell-specific manner. Indeed, the neuroprotective function of RORalpha in astrocytes correlates with a downregulation of HIF-1alpha selectively in these cells. Altogether, our results show that RORalpha is a key molecular player in hypoxia, protecting neurons through its dual action in neurons and astrocytes. PMID- 21976518 TI - Mutant PKCgamma in spinocerebellar ataxia type 14 disrupts synapse elimination and long-term depression in Purkinje cells in vivo. AB - Cerebellar Purkinje cells (PCs) express a large amount of the gamma isoform of protein kinase C (PKCgamma) and a modest level of PKCalpha. The PKCgamma is involved in the pruning of climbing fiber (CF) synapses from developing PCs, and PKCalpha plays a critical role in long-term depression (LTD) at parallel fiber (PF)-PC synapses. Moreover, the PKC signaling in PCs negatively modulates the nonselective transient receptor potential cation channel type 3 (TRPC3), the opening of which elicits slow EPSCs at PF-PC synapses. Autosomal dominant spinocerebellar ataxia type 14 (SCA14) is caused by mutations in PKCgamma. To clarify the pathology of this disorder, mutant (S119P) PKCgamma tagged with GFP was lentivirally expressed in developing and mature mouse PCs in vivo, and the effects were assessed 3 weeks after the injection. Mutant PKCgamma-GFP aggregated in PCs without signs of degeneration. Electrophysiology results showed impaired pruning of CF synapses from developing PCs, failure of LTD expression, and increases in slow EPSC amplitude. We also found that mutant PKCgamma colocalized with wild-type PKCgamma, which suggests that mutant PKCgamma acts in a dominant negative manner on wild-type PKCgamma. In contrast, PKCalpha did not colocalize with mutant PKCgamma. The membrane residence time of PKCalpha after depolarization-induced translocation, however, was significantly decreased when it was present with the mutant PKCgamma construct. These results suggest that mutant PKCgamma in PCs of SCA14 patients could differentially impair the membrane translocation kinetics of wild-type gamma and alpha PKCs, which would disrupt synapse pruning, synaptic plasticity, and synaptic transmission. PMID- 21976519 TI - Affiliative behavior requires juvenile, but not adult neurogenesis. AB - The capacity to interact with conspecifics is essential for stable social networks, reproduction, and survival in mammals. In rodents, social exploration and play behavior increase during the juvenile period, suggesting that this timeframe represents an important window for socialization. However, the cellular and molecular mechanisms necessary to support this developmental process have not been elucidated. Neurogenesis during the juvenile period, like that in adults, is mainly confined to the subgranular and subventricular zones. Nevertheless, the levels of neurogenesis are significantly higher during the juvenile period, suggesting unique functions not shared with adult neurogenesis. Here we use a transgenic mouse approach that allows for ablation of neurogenesis during different developmental phases. We find that ablating neurogenesis during either juvenile or adult phases altered anxiety and memory in adult female mice, demonstrating an age-independent function of new neurons for certain behaviors. Blocking neurogenesis during the juvenile period resulted in a profound impairment in the ability of these mice to interact with other adult females or to retrieve pups, without causing gross olfactory deficits. Interestingly, ablating neurogenesis in adult females had no effect on these social behaviors. This work defines a novel role for juvenile neurogenesis in establishing brain circuits necessary for socialization, and demonstrates that juvenile and adult neurogenesis make different contributions to social competency in adult female mice. Additional work is needed to determine whether ablation of juvenile neurogenesis in the subgranular zone and/or the subventricular zone is responsible for the social abnormalities seen after global elimination of juvenile neurogenesis. PMID- 21976521 TI - Metabolic dysfunction associated with adiponectin deficiency enhances kainic acid induced seizure severity. AB - Metabolic syndrome has deleterious effects on the CNS, and recent evidence suggests that obesity rates are higher at presentation in children who develop epilepsy. Adiponectin is secreted by adipose tissue and acts in the brain and peripheral organs to regulate glucose and lipid metabolism. Adiponectin deficiency predisposes toward metabolic syndrome, characterized by obesity, insulin resistance, impaired glucose tolerance, hyperlipidemia, and cardiovascular morbidity. To investigate the relationship between metabolic syndrome and seizures, wild-type C57BL/6J and adiponectin knock-out mice were fed a high-fat diet, followed by treatment with low doses of kainic acid to induce seizures. Adiponectin deficiency in mice fed a high-fat diet resulted in greater fat accumulation, impaired glucose tolerance, hyperlipidemia, increased seizure severity, and increased hippocampal pathology. In contrast, there were no adverse effects of adiponectin deficiency on metabolic phenotype or seizure activity in mice fed a normal (low-fat) chow diet. These findings demonstrate that metabolic syndrome modulates the outcome of seizures and brain injury. PMID- 21976520 TI - Annexin A2 promotes glioma cell invasion and tumor progression. AB - Gliomas are highly invasive, lethal brain tumors. Tumor-associated proteases play an important role in glioma progression. Annexin A2 is overexpressed in many cancers and correlates with increased plasmin activity on the tumor cell surface, which mediates degradation of extracellular matrix and promotes neoangiogenesis to facilitate tumor growth. In this study, we used two glioma cell lines, mouse GL261-EGFP and rat C6/LacZ, as well as stable clones transfected with an annexin A2 knockdown construct. We find that the annexin A2 knockdown decreased glioma cell migration in vitro and decreased membrane-bound plasmin activity. In vivo, we injected the glioma cells into the rodent brain and followed glioma progression. Knockdown of annexin A2 in glioma cells decreased tumor size and slowed tumor progression, as evidenced by decreased invasion, angiogenesis, and proliferation, as well as increased apoptosis in the tumor tissue of the annexin A2 knockdown group. Moreover, we report that the levels of expression of annexin A2 in human glioma samples correlate with their degree of malignancy. Together, our findings demonstrate that inhibition of annexin A2 expression in glioma cells could become a new target for glioma therapy. PMID- 21976523 TI - Effective connectivity during processing of facial affect: evidence for multiple parallel pathways. AB - The perception of facial affect engages a distributed cortical network. We used functional magnetic resonance imaging and dynamic causal modeling to characterize effective connectivity during explicit (conscious) categorization of affective stimuli in the human brain. Specifically, we examined the modulation of connectivity from posterior regions of the face-processing network to the lateral ventral prefrontal cortex (VPFC) during affective categorization and we tested for a potential role of the amygdala (AMG) in mediating this modulation. We found that explicit processing of facial affect led to prominent modulation (increase) in the effective connectivity from the inferior occipital gyrus (IOG) to the VPFC, while there was less evidence for modulation of the afferent connections from fusiform gyrus and AMG to VPFC. More specifically, the forward connection from IOG to the VPFC exhibited a selective increase under anger (as opposed to fear or sadness). Furthermore, Bayesian model comparison suggested that the modulation of afferent connections to the VPFC was mediated directly by facial affect, as opposed to an indirect modulation mediated by the AMG. Our results thus suggest that affective information is conveyed to the VPFC along multiple parallel pathways and that AMG activity is not sufficient to account for the gating of information transfer to the VPFC during explicit emotional processing. PMID- 21976522 TI - Heightened nicotinic regulation of auditory cortex during adolescence. AB - Adolescent smoking is associated with auditory-cognitive deficits and structural alterations to auditory thalamocortical systems, suggesting that higher auditory function is vulnerable to nicotine exposure during adolescence. Although nicotinic acetylcholine receptors (nAChRs) regulate thalamocortical processing in adults, it is not known whether they regulate processing at earlier ages since their expression pattern changes throughout postnatal development. Here we investigate nicotinic regulation of tone-evoked current source density (CSD) profiles in mouse primary auditory cortex from just after hearing onset until adulthood. At the youngest ages, systemic nicotine did not affect CSD profiles. However, beginning in early adolescence nicotine enhanced characteristic frequency (CF)-evoked responses in layers 2-4 by enhancing thalamocortical, early intracortical, and late intracortical response components. Nicotinic responsiveness developed rapidly and peaked over the course of adolescence, then declined thereafter. Generally, responsiveness in females developed more quickly, peaked earlier, and declined more abruptly and fully than in males. In contrast to the enhancement of CF-evoked responses, nicotine suppressed shorter-latency intracortical responses to spectrally distant (non-CF) stimuli while enhancing longer-latency responses. Intracortical infusion of nAChR antagonists showed that enhancement of CF-evoked intracortical processing involves alpha4beta2*, but not alpha7, nAChRs, whereas both receptor subtypes regulate non-CF-evoked late intracortical responses. Notably, antagonist effects in females implied regulation by endogenous acetylcholine. Thus, nicotinic regulation of cortical processing varies with age and sex, with peak effects during adolescence that may contribute to the vulnerability of adolescents to smoking. PMID- 21976524 TI - Grasp movement decoding from premotor and parietal cortex. AB - Despite recent advances in harnessing cortical motor-related activity to control computer cursors and robotic devices, the ability to decode and execute different grasping patterns remains a major obstacle. Here we demonstrate a simple Bayesian decoder for real-time classification of grip type and wrist orientation in macaque monkeys that uses higher-order planning signals from anterior intraparietal cortex (AIP) and ventral premotor cortex (area F5). Real-time decoding was based on multiunit signals, which had similar tuning properties to cells in previous single-unit recording studies. Maximum decoding accuracy for two grasp types (power and precision grip) and five wrist orientations was 63% (chance level, 10%). Analysis of decoder performance showed that grip type decoding was highly accurate (90.6%), with most errors occurring during orientation classification. In a subsequent off-line analysis, we found small but significant performance improvements (mean, 6.25 percentage points) when using an optimized spike-sorting method (superparamagnetic clustering). Furthermore, we observed significant differences in the contributions of F5 and AIP for grasp decoding, with F5 being better suited for classification of the grip type and AIP contributing more toward decoding of object orientation. However, optimum decoding performance was maximal when using neural activity simultaneously from both areas. Overall, these results highlight quantitative differences in the functional representation of grasp movements in AIP and F5 and represent a first step toward using these signals for developing functional neural interfaces for hand grasping. PMID- 21976525 TI - Distinct roles of three frontal cortical areas in reward-guided behavior. AB - Functional magnetic resonance imaging was used to measure activity in three frontal cortical areas, the lateral orbitofrontal cortex (lOFC), medial orbitofrontal cortex (mOFC)/ventromedial frontal cortex (vmPFC), and anterior cingulate cortex (ACC), when expectations about type of reward, and not just reward presence or absence, could be learned. Two groups of human subjects learned 12 stimulus-response pairings. In one group (Consistent), correct performances of a given pairing were always reinforced with a specific reward outcome, whereas in the other group (Inconsistent), correct performances were reinforced with randomly selected rewards. The mOFC/vmPFC and lOFC were not distinguished by simple differences in relative preference for positive and negative outcomes. Instead lOFC activity reflected updating of reward-related associations specific to reward type; lOFC was active whenever informative outcomes allowed updating of reward-related associations, regardless of whether the outcomes were positive or negative, and the effects were greater when consistent stimulus-outcome and response-outcome mappings were present. A psychophysiological interaction analysis demonstrated changed coupling between lOFC and brain areas for visual object representation, such as perirhinal cortex, and reward-guided learning, such as the amygdala, ventral striatum, and habenula/mediodorsal thalamus. In contrast, mOFC/vmPFC activity reflected expected values of outcomes and occurrence of positive outcomes, regardless of consistency of outcome mappings. The third frontal cortical region, the ACC, reflected the use of reward type information to guide response selection. ACC activity reflected the probability of selecting the correct response, was greater when consistent outcome mappings were present, and was related to individual differences in propensity to select the correct response. PMID- 21976526 TI - ApoER2 function in the establishment and maintenance of retinal synaptic connectivity. AB - The cellular and molecular mechanisms responsible for the development of inner retinal circuitry are poorly understood. Reelin and apolipoprotein E (apoE), ligands of apoE receptor 2 (ApoER2), are involved in retinal development and degeneration, respectively. Here we describe the function of ApoER2 in the developing and adult retina. ApoER2 expression was highest during postnatal inner retinal synaptic development and was considerably lower in the mature retina. Both during development and in the adult, ApoER2 was expressed by A-II amacrine cells. ApoER2 knock-out (KO) mice had rod bipolar morphogenic defects, altered A II amacrine dendritic development, and impaired rod-driven retinal responses. The presence of an intact ApoER2 NPxY motif, necessary for binding Disabled-1 and transducing the Reelin signal, was also necessary for development of the rod bipolar pathway, while the alternatively spliced exon 19 was not. Mice deficient in another Reelin receptor, very low-density lipoprotein receptor (VLDLR), had normal rod bipolar morphology but altered A-II amacrine dendritic development. VLDLR KO mice also had reductions in oscillatory potentials and delayed synaptic response intervals. Interestingly, age-related reductions in rod and cone function were observed in both ApoER2 and VLDLR KOs. These results support a pivotal role for ApoER2 in the establishment and maintenance of normal retinal synaptic connectivity. PMID- 21976527 TI - Circuitry underlying spectrotemporal integration in the auditory midbrain. AB - Combination sensitivity in central auditory neurons is a form of spectrotemporal integration in which excitatory responses to sounds at one frequency are facilitated by sounds within a distinctly different frequency band. Combination sensitive neurons respond selectively to acoustic elements of sonar echoes or social vocalizations. In mustached bats, this response property originates in high-frequency representations of the inferior colliculus (IC) and depends on low and high frequency-tuned glycinergic inputs. To identify the source of these inputs, we combined glycine immunohistochemistry with retrograde tract tracing. Tracers were deposited at high-frequency (>56 kHz), combination-sensitive recording sites in IC. Most glycine-immunopositive, retrogradely labeled cells were in ipsilateral ventral and intermediate nuclei of the lateral lemniscus (VNLL and INLL), with some double labeling in ipsilateral lateral and medial superior olivary nuclei (LSO and MSO). Generally, double-labeled cells were in expected high-frequency tonotopic areas, but some VNLL and INLL labeling appeared to be in low-frequency representations. To test whether these nuclei provide low frequency-tuned input to the high-frequency IC, we combined retrograde tracing from IC combination-sensitive sites with anterograde tracing from low frequency tuned sites in the anteroventral cochlear nucleus (AVCN). Only VNLL and INLL contained retrogradely labeled cells near (<=50 MUm) anterogradely labeled boutons. These cells likely receive excitatory low-frequency input from AVCN. Results suggest that combination-sensitive facilitation arises through convergence of high-frequency glycinergic inputs from VNLL, INLL, or MSO and low frequency glycinergic inputs from VNLL or INLL. This work establishes an anatomical basis for spectrotemporal integration in the auditory midbrain and a functional role for monaural nuclei of the lateral lemniscus. PMID- 21976529 TI - Treatment with octreotide does not reduce tumor uptake of (68)Ga-DOTATATE as measured by PET/CT in patients with neuroendocrine tumors. AB - We hypothesized that (68)Ga-DOTATATE uptake of neuroendocrine tumors is sensitive to therapy with a nonradioactive somatostatin analog. METHODS: (68)Ga-DOTATATE PET/CT was used to examine 105 patients, 35 of whom had been pretreated with long acting octreotide. The maximum standardized uptake value (SUV(max)) of target tissues, as well as metastases, was compared between the groups of patients with (group 1) and without (group 2) octreotide treatment. RESULTS: The SUV(max) of the spleen and liver was significantly lower in group 1 than in group 2 (both P < 0.001). There were no significant group differences in SUV(max) for primary tumors (28.6 +/- 6.8 vs. 32.9 +/- 31.5) or metastases in the liver (27.2 +/- 14.8 vs. 25.7 +/- 10.7), lymph nodes (41.4 +/- 19.5 vs. 25.0 +/- 6.3), or skeleton (39.5 +/- 22.0 vs. 15.4 +/- 7.8). In 9 patients available for intraindividual comparison, tumor uptake was unaffected by treatment with somatostatin analogs (21.7 vs. 20.6; P = 0.93). CONCLUSION: Treatment with a long-acting somatostatin analog did not significantly reduce (68)Ga-DOTATATE binding in neuroendocrine tumors but tended to improve the tumor-to-background ratio. PMID- 21976528 TI - Chronic stress exacerbates tau pathology, neurodegeneration, and cognitive performance through a corticotropin-releasing factor receptor-dependent mechanism in a transgenic mouse model of tauopathy. AB - Because overactivation of the hypothalamic-pituitary-adrenal (HPA) axis occurs in Alzheimer's disease (AD), dysregulation of stress neuromediators may play a mechanistic role in the pathophysiology of AD. However, the effects of stress on tau phosphorylation are poorly understood, and the relationship between corticosterone and corticotropin-releasing factor (CRF) on both beta-amyloid (Abeta) and tau pathology remain unclear. Therefore, we first established a model of chronic stress, which exacerbates Abeta accumulation in Tg2576 mice and then extended this stress paradigm to a tau transgenic mouse model with the P301S mutation (PS19) that displays tau hyperphosphorylation, insoluble tau inclusions and neurodegeneration. We show for the first time that both Tg2576 and PS19 mice demonstrate a heightened HPA stress profile in the unstressed state. In Tg2576 mice, 1 month of restraint/isolation (RI) stress increased Abeta levels, suppressed microglial activation, and worsened spatial and fear memory compared with nonstressed mice. In PS19 mice, RI stress promoted tau hyperphosphorylation, insoluble tau aggregation, neurodegeneration, and fear-memory impairments. These effects were not mimicked by chronic corticosterone administration but were prevented by pre-stress administration of a CRF receptor type 1 (CRF(1)) antagonist. The role for a CRF(1)-dependent mechanism was further supported by the finding that mice overexpressing CRF had increased hyperphosphorylated tau compared with wild-type littermates. Together, these results implicate HPA dysregulation in AD neuropathogenesis and suggest that prolonged stress may increase Abeta and tau hyperphosphorylation. These studies also implicate CRF in AD pathophysiology and suggest that pharmacological manipulation of this neuropeptide may be a potential therapeutic strategy for AD. PMID- 21976530 TI - Palliation and survival after repeated (188)Re-HEDP therapy of hormone-refractory bone metastases of prostate cancer: a retrospective analysis. AB - This retrospective study compared the effects of single and multiple administrations of (186)Re-hydroxyethylidenediphosphonate ((186)Re-HEDP) on palliation and survival of prostate cancer patients presenting with more than 5 skeletal metastases. METHODS: A total of 60 patients were divided into 3 groups. Group A (n = 19) consisted of patients who had received a single injection; group B (n = 19), patients who had 2 injections; and group C (n = 22), patients who had 3 or more successive injections. The (188)Re-HEDP was prepared using non-carrier added (188)Re obtained from an in-house (188)W/(188)Re generator after dilution with carrier perrhenate. Patients' data available from the referring physicians including prostate-specific antigen levels-were entered into a Windows-based matrix and analyzed using a statistical program. The Gleason scores were similar for all 3 groups. RESULTS: Mean survival from the start of treatment was 4.50 +/- 0.81 mo (95% confidence interval [CI], 2.92-6.08) for group A, 9.98 +/- 2.21 mo (95% CI, 5.65-14.31) for group B, and 15.66 +/- 3.23 (95% CI, 9.33-22.0) for group C. Although the 3 groups did not differ in Gleason score, the number of lost life-years was significantly lower in group C than in groups A and B. Pain palliation was achieved in 89.5% of group A, 94.7% of group B, and 90.9% of group C. CONCLUSION: Posttreatment overall survival could be improved from 4.50 to 15.66 mo by multiple-injection bone-targeted therapy with (188)Re-HEDP, when compared with a single injection. Significant pain palliation was common and independent of administration frequency. PMID- 21976531 TI - Novel phosphoinositide 3-kinase/mTOR dual inhibitor, NVP-BGT226, displays potent growth-inhibitory activity against human head and neck cancer cells in vitro and in vivo. AB - PURPOSE: Dysregulation of the phosphoinositide 3-kinase (PI3K)/AKT/mTOR signaling pathway frequently accounts for the tumorigenesis in head and neck cancer. To develop a new treatment, we investigated the effect of a novel dual PI3K/mTOR inhibitor, NVP-BGT226 (BGT226), in head and neck cancer cells. EXPERIMENTAL DESIGN: The in vitro antitumor effect of BGT226 was determined in various cancer cell lines. Animal models were also applied to examine drug potency. The inhibitory ability of BGT226 on the PI3K/AKT/mTOR signaling pathway was analyzed. RESULTS: The growth inhibition assay revealed that BGT226 was active against all tested cancer cell lines. Cross-resistance was not observed in the cisplatin resistant cell line. The activation of the AKT/mTOR signal cascade was suppressed by BGT226 in a concentration- and time-dependent manner. Flow cytometric analysis revealed an accumulation of cells in the G(0)-G(1) phase with concomitant loss in the S-phase. Results of the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and the analysis of caspase 3/7 and PARP indicated that BGT226 induced cancer cell death through an apoptosis-independent pathway. BGT226 induced autophagy as indicated by the aggregation and upregulation of the microtubule-associated protein light chain 3B-II, and p62 degradation. Gene silencing of Beclin1 or cotreatment of the autophagosome inhibitor, 3-methyladenine, inhibited the BGT226-induced autophagy and led to the retrieval of colony survival. In a xenografted animal model, BGT226 significantly delayed tumor growth in a dose-dependent manner, along with suppressed cytoplasmic expression of p-p70 S6 kinase and the presence of autophagosome formation. CONCLUSIONS: These data indicate that BGT226 is a potential drug in the treatment of head and neck cancer. PMID- 21976532 TI - Cytokeratin-19 and mammaglobin gene expression in circulating tumor cells from metastatic breast cancer patients enrolled in North Central Cancer Treatment Group trials, N0234/336/436/437. AB - PURPOSE: To investigate the associations between baseline and posttreatment circulating tumor cell (CTC) gene expression and outcome of patients enrolled in four North Central Cancer Treatment Group metastatic breast cancer (MBC) trials in which specimens were shipped (at 4 degrees C) from community-based sites to a reference laboratory (Mayo Clinic, Rochester, MN). EXPERIMENTAL DESIGN: Blood was collected at treating sites from MBC patients before (baseline), during, and at the end of treatment with erlotinib + gemcitabine (N0234), sorafenib (N0336), irinotecan + cetuximab (N0436), or paclitaxel-poliglumex + capecitabine (N0437). CTCs from 10 mL of EDTA blood were enriched with CD45 depletion, 24 to 30 hours postblood collection. Reverse transcription/quantitative PCR was used to determine cytokeratin-19 (CK19) and mammaglobin (MGB1) mRNA levels in CTCs from up to 13 (N0234), 16 (N0336), 18 (N0436), and 39 (N0437) patients. The gene expressions were normalized to beta(2)-microglobulin and calibrated to healthy blood using the 2(-DeltaDeltaCq) algorithm; positivity was defined as 2 or more. RESULTS: CK19+mRNA cells were detected in 56% to 75% and MGB1+mRNA cells in 23% to 38% of 86 patients at baseline. CK19+mRNA cells were detected in 30% to 67% and MGB1+mRNA cells in 14% to 64% of 110 postbaseline serial samples. The presence of baseline CK19+mRNA cells (P = 0.01) but not MGB1+mRNA cells (P = 0.14) was significantly associated with shorter overall survival. A decrease in MGB1+mRNA levels (baseline-week 8) seemed to be associated with clinical response (P = 0.05). CONCLUSIONS: CTC gene expression analysis conducted by a reference laboratory is feasible when blood is collected from treating sites and processed 24 to 30 hours postcollection. The presence of baseline CK19+mRNA CTCs was associated with poor prognosis; a decrease in MGB1+mRNA CTCs may help predict response to therapy of MBC patients. PMID- 21976533 TI - Achieving sufficient accrual to address the primary endpoint in phase III clinical trials from U.S. Cooperative Oncology Groups. AB - PURPOSE: Assessing impact of poor accrual on premature trial closure requires a relevant metric. We propose defining accrual sufficiency on apparent ability to address primary endpoints (PE) rather than attaining accrual targets. EXPERIMENTAL DESIGN: All phase III trials open January 1, 1993, to December 31, 2002, by five U.S. oncology Clinical Trials Cooperative Groups (CTCG) were evaluated for accrual sufficiency and scientific results. Sufficient accrual included meeting accrual target, CTCGs documentation attesting adequate accrual, or conclusive results at interim analysis; insufficient accrual included poor accrual as cited closure reason or other reasons rendering a trial unable to address its primary endpoints. Closure rates based on our accrual sufficiency definition are compared with rates of meeting accrual targets and addressing the primary endpoints. A percentage of target accrual above which trials commonly answer the intended scientific question was identified to serve as an alternative to meeting full target accrual in designating accrual success. RESULTS: Of 238 eligible trials, 158 (66%) closed with sufficient accrual. Among 80 trials with insufficient accrual, 70 (29%) closed specifically because of poor accrual. Inadequate accrual rates are overemphasized when defining accrual success solely by meeting accrual targets. Nearly 75% of trials conclusively addressed the primary endpoints with positive results in 39% of trials. Exceeding 80% of target accrual serves as a reliable proxy for answering the intended scientific question. CONCLUSIONS: Approximately one third of phase III trials closed with insufficient accrual to address the primary endpoints, primarily due to poor accrual. Defining accrual sufficiency broader than meeting accrual targets represents a fairer account of trial closures. PMID- 21976534 TI - Copy number aberrations in benign serous ovarian tumors: a case for reclassification? AB - PURPOSE: Serous ovarian carcinomas are the predominant epithelial ovarian cancer subtype and it has been widely believed that some or all of these may arise from precursors derived from the ovarian surface epithelium or fimbriae, although direct molecular evidence for this is limited. This study aimed to conduct copy number (CN) analysis using a series of benign and borderline serous ovarian tumors to identify underlying genomic changes that may be indicative of early events in tumorigenesis. EXPERIMENTAL DESIGN: High resolution CN analysis was conducted on DNA from the epithelial and fibroblast components of a cohort of benign (N = 39) and borderline (N = 24) serous tumors using the Affymetrix OncoScan assay and SNP6.0 arrays. RESULTS: CN aberrations were detected in the epithelium of only 2.9% (1 of 35) of serous cystadenomas and cystadenofibromas. In contrast, CN aberrations were detected in the epithelium of 67% (16 of 24) of the serous borderline tumors (SBT). Unexpectedly, CN aberrations were detected in the fibroblasts of 33% (13 of 39) of the benign serous tumors and in 15% (3 of 20) of the SBTs. Of the 16 cases with CN aberrations in the fibroblasts, 12 of these carried a gain of chromosome 12. CONCLUSIONS: Chromosome 12 trisomy has been previously identified in pure fibromas, supporting the concept that a significant proportion of benign serous tumors are in fact primary fibromas with an associated cystic mass. This is the first high resolution genomic analysis of benign serous ovarian tumors and has shown not only that the majority of benign serous tumors have no genetic evidence of epithelial neoplasia but that a significant proportion may be more accurately classified as primary fibromas. PMID- 21976535 TI - A phase I dose-escalation study of Tivantinib (ARQ 197) in adult patients with metastatic solid tumors. AB - BACKGROUND: Tivantinib, an oral, non-ATP competitive, selective c-MET inhibitor, exhibited antitumor activity in preclinical models. This open-label, phase I, dose-escalation study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of tivantinib in patients with advanced or metastatic solid tumors refractory to standard therapy. METHODS: Thirteen dose levels of tivantinib ranging from 10 to 360 mg twice a day were administered to patient cohorts in 21-day cycles (14 days on/7 days off); three active pharmaceutical ingredient forms of tivantinib (amorphous, crystalline A, and crystalline B) were also investigated. Treatment was continued until the occurrence of unacceptable toxicity, tumor progression, patient withdrawal, or death. RESULTS: A total of 79 patients with advanced solid tumors were enrolled. A maximum tolerated dose was not determined. Tivantinib was well tolerated, with mild to moderate toxicities. Two patients discontinued the study drug due to treatment-emergent adverse events. Dose-limiting grade of 3 or more toxicities including leukopenia, neutropenia, thrombocytopenia, vomiting, and dehydration, were observed in 2 patients treated with tivantinib 360 mg twice a day. The rate of absorption of tivantinib peaked approximately 2 to 4 hours after initial dosing, followed by a linear decrease in plasma concentrations. Increases in tivantinib exposure were not dose proportional. There was significant interpatient pharmacokinetic variability; however the clinical safety of tivantinib seemed unaffected. Three patients (3.8%) achieved a partial response and 40 patients (50.6%) maintained stable disease for a median of 19.9 weeks. CONCLUSIONS: Tivantinib 360 mg twice a day was well tolerated in patients with refractory advanced solid tumors. The results of this trial warrant further clinical investigation. Clin Cancer Res; 17(24); 7754-64. (c)2011 AACR. PMID- 21976536 TI - Cancer stem cells: targets and potential biomarkers for radiotherapy. AB - Cancer stem cells (CSC) have the unique ability to cause tumor recurrences if they survive treatment. Radiotherapy has curative potential because it has been functionally shown to sufficiently inactivate CSCs. It is well known that CSCs mediate the radiation resistance of tumors by tumor-specific factors, such as the pretreatment number of CSCs and repopulation or reoxygenation during fractionated radiotherapy. CSCs appear to have a higher intrinsic radioresistance than non CSCs, a factor that is especially important for the development of predictive biomarkers that, if this finding holds true, can only be successfully established if they are stem-cell specific. Recent clinical data imply that stem-cell-related surface markers may be directly used as predictors for the radiocurability of tumors with comparable risk factors, such as histology and size. Future studies need to address the question of which additional markers need to be considered if more heterogeneous patient collectives are investigated. With the goal of developing a direct targeting approach, investigators are currently evaluating several drugs that are intended to target CSCs by inhibiting stem-cell-related signal transduction pathways. We need to preclinically test such drugs as combined-modality therapies in combination with radiotherapy to evaluate their curative potential, and optimize them by increasing their specificity to CSCs over normal tissue stem cells to avoid increased radiation toxicity. PMID- 21976537 TI - Molecular insights on the peripheral and intratumoral effects of systemic high dose rIL-2 (aldesleukin) administration for the treatment of metastatic melanoma. AB - PURPOSE: We have previously shown that within tumors, recombinant interleukin-2 (rIL-2, aldesleukin) consistently activates tumor-associated macrophages and upregulates IFN-stimulated genes while inducing minimal migration, activation, or proliferation of T cells. These effects are independent of tumor response to treatment. Here, we prospectively evaluated transcriptional alterations induced by rIL-2 in peripheral blood mononuclear cells (PBMC) and within melanoma metastases. EXPERIMENTAL DESIGN: We evaluated gene expression changes by serially comparing pre- to posttreatment samples in 13 patients and also compared transcriptional differences among lesions displaying different responsiveness to therapy, focusing on 2 lesions decreasing in size and 2 remaining stable (responding lesions) compared with nonresponding ones. RESULTS: As previously described, the effects of rIL-2 were dramatic within PBMCs, whereas effects within the tumor microenvironment were lesion specific and limited. However, distinct signatures specific to response could be observed in responding lesions pretreatment that were amplified following rIL-2 administration. These signatures match the functional profile observed in other human or experimental models in which immune-mediated tissue-specific destruction (TSD) occurs, underscoring common pathways leading to rejection. Moreover, the signatures observed in pretreatment lesions were qualitatively similar to those associated with TSD, underlining a determinism to immune responsiveness that depends upon the genetic background of the host or the intrinsic genetic makeup of individual tumors. CONCLUSIONS: This is the first prospectively collected insight on global transcriptional events occurring during high-dose rIL-2 therapy in melanoma metastases responding to treatment. PMID- 21976538 TI - Quantitative detection of EGFR mutations in circulating tumor DNA derived from lung adenocarcinomas. AB - PURPOSE: Examination of somatic epidermal growth factor receptor (EGFR) mutations is now a diagnostic routine for treatment of cancer using EGFR tyrosine kinase inhibitors (EGFR-TKI). Circulating tumor DNA is a promising target for noninvasive diagnostics. We evaluated its utility by quantitatively detecting activating and resistant mutations, which were measured with BEAMing (beads, emulsion, amplification, and magnetics). EXPERIMENTAL DESIGN: Twenty-three patients with lung cancer with progressive disease after EGFR-TKI treatment and 21 patients who had never been treated with EGFR-TKIs were studied. Their primary tumors were confirmed to have activating mutations. In the plasma DNA of each patient, the activating mutation found in the corresponding primary tumor and the T790M resistance mutation were quantified by BEAMing. RESULTS: In 32 of 44 patients, activating mutations were detected in the plasma DNA [72.7%; 95% confidence interval (CI), 58.0%-83.6%]. The T790M mutation was detected in 10 of 23 patients in the first group (43.5%; 95% CI, 25.6%-53.4%). The ratio of T790M to activating mutations ranged from 13.3% to 94.0%. The peak of the distribution of the mutation allele fraction in the plasma DNA was in the 0.1% to 1% range. CONCLUSIONS: The major advantage of BEAMing is its ability to calculate the fraction of T790M-positive alleles from the alleles with activating mutations. This feature enables the detection of increases and decreases in the number of T790M mutations in cancer cells, regardless of normal cell DNA contamination, which may be useful for monitoring disease progression. Circulating tumor DNA could potentially be used as an alternative method for EGFR mutation detection. PMID- 21976539 TI - Metadherin promotes hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition. AB - PURPOSE: To investigate the expression of metadherin (MTDH) for its prognostic value in hepatocellular carcinoma (HCC) and its role in promoting HCC metastasis. EXPERIMENTAL DESIGN: This study employed a tissue microarray containing samples from 323 HCC patients to examine the expression of MTDH and its correlation with other clinicopathologic characteristics. The role of MTDH in the regulation of HCC metastasis was investigated both in vitro and in vivo using short hairpin RNA (shRNA)-mediated downregulation of MTDH in HCC cell lines with various metastatic potentials. RESULTS: The expression of MTDH was markedly higher in HCC tumors than in normal liver tissue. Particularly high MTDH expression was observed in tumors with microvascular invasion, pathologic satellites, poor differentiation, or tumor-node-metastasis stages II to III. Furthermore, the clinical outcome was consistently poorer for the MTDH(high) group than for the MTDH(low) group in the 1-, 3-, and 5-year overall survival (OS) rates and in the 1-, 3-, 5-year cumulative recurrence rates. In a nude mice model, the shRNA-mediated downregulation of MTDH resulted in a reduced migratory capacity in HCC cell lines, as well as a reduction in pulmonary and abdominal metastasis. Furthermore, we found that the expression level of MTDH correlated with four epithelial mesenchymal transition (EMT) markers. Knockdown of MTDH expression in HCC cell lines resulted in downregulation of N-cadherin and snail, upregulation of E cadherin, and translocation of beta-catenin. CONCLUSIONS: MTDH may promote HCC metastasis through the induction of EMT process and may be a candidate biomarker for prognosis as well as a target for therapy. PMID- 21976540 TI - Phase I/II and pharmacodynamic study of dovitinib (TKI258), an inhibitor of fibroblast growth factor receptors and VEGF receptors, in patients with advanced melanoma. AB - PURPOSE: Dovitinib (TKI258) is an orally available inhibitor of fibroblast growth factor (FGF), VEGF, and platelet-derived growth factor receptors. This phase I/II dose-escalation study was conducted to evaluate the safety, pharmacodynamics, and preliminary efficacy of dovitinib in the treatment of advanced melanoma. EXPERIMENTAL DESIGN: Patients with advanced melanoma resistant or refractory to standard therapies or for whom no standard therapy was available were enrolled. Dovitinib was administered at doses ranging from 200 to 500 mg/d. RESULTS: Forty seven patients were enrolled. The most frequently reported adverse events were fatigue (77%; grade >=3, 28%), diarrhea (77%; grade >=3, 11%), and nausea (77%; grade >=3, 9%). Six dose-limiting toxicities were observed in the 400-mg and 500 mg dose cohorts, which consisted of grade 3 nausea, fatigue, and diarrhea and grade 4 fatigue events. The maximum tolerated dose was 400 mg/d. The best tumor response was stable disease, which was observed in 12 patients. Increases in plasma FGF23, VEGF, and placental growth factor and decreases in soluble VEGF receptor 2 were noted during the first cycle of treatment, consistent with FGF receptor (FGFR) and VEGF receptor (VEGFR) inhibition. Dynamic contrast-enhanced MRI analysis showed a dose-dependent decrease in tumor blood flow and vascular permeability with dovitinib therapy. A decrease in FGFR phosphorylation was observed in paired tumor biopsy samples from a patient treated with dovitinib at a dose of 400 mg/d. CONCLUSIONS: At a dose of 400 mg/d, dovitinib showed an acceptable safety profile and limited clinical benefit and inhibited FGFR and VEGFR. PMID- 21976541 TI - Pretargeted radioimmunotherapy using genetically engineered antibody-streptavidin fusion proteins for treatment of non-hodgkin lymphoma. AB - PURPOSE: Pretargeted radioimmunotherapy (PRIT) using streptavidin (SAv)-biotin technology can deliver higher therapeutic doses of radioactivity to tumors than conventional RIT. However, "endogenous" biotin can interfere with the effectiveness of this approach by blocking binding of radiolabeled biotin to SAv. We engineered a series of SAv FPs that downmodulate the affinity of SAv for biotin, while retaining high avidity for divalent DOTA-bis-biotin to circumvent this problem. EXPERIMENTAL DESIGN: The single-chain variable region gene of the murine 1F5 anti-CD20 antibody was fused to the wild-type (WT) SAv gene and to mutant SAv genes, Y43A-SAv and S45A-SAv. FPs were expressed, purified, and compared in studies using athymic mice bearing Ramos lymphoma xenografts. RESULTS: Biodistribution studies showed delivery of more radioactivity to tumors of mice pretargeted with mutant SAv FPs followed by (111)In-DOTA-bis-biotin [6.2 +/- 1.7% of the injected dose per gram (%ID/gm) of tumor 24 hours after Y43A-SAv FP and 5.6 +/- 2.2%ID/g with S45A-SAv FP] than in mice on normal diets pretargeted with WT-SAv FP (2.5 +/- 1.6%ID/g; P = 0.01). These superior biodistributions translated into superior antitumor efficacy in mice treated with mutant FPs and (90)Y-DOTA-bis-biotin [tumor volumes after 11 days: 237 +/- 66 mm(3) with Y43A-SAv, 543 +/- 320 mm(3) with S45A-SAv, 1129 +/- 322 mm(3) with WT SAv, and 1435 +/- 212 mm(3) with control FP (P < 0.0001)]. CONCLUSIONS: Genetically engineered mutant-SAv FPs and bis-biotin reagents provide an attractive alternative to current SAv-biotin PRIT methods in settings where endogenous biotin levels are high. PMID- 21976542 TI - Novel chromosomal rearrangements and break points at the t(6;9) in salivary adenoid cystic carcinoma: association with MYB-NFIB chimeric fusion, MYB expression, and clinical outcome. AB - OBJECTIVE: To investigate the molecular genetic heterogeneity associated with the t(6:9) in adenoid cystic carcinoma (ACC) and correlate the findings with patient clinical outcome. EXPERIMENTAL DESIGN: Multimolecular and genetic techniques complemented with massive pair-ended sequencing and single-nucleotide polymorphism array analyses were used on tumor specimens from 30 new and 52 previously analyzed fusion transcript-negative ACCs by reverse transcriptase PCR (RT-PCR). MYB mRNA expression level was determined by quantitative RT-PCR. The results of 102 tumors (30 new and 72 previously reported cases) were correlated with the clinicopathologic factors and patients' survival. RESULTS: The FISH analysis showed 34 of 82 (41.5%) fusion-positive tumors and molecular techniques identified fusion transcripts in 21 of the 82 (25.6%) tumors. Detailed FISH analysis of 11 out the 15 tumors with gene fusion without transcript formation showed translocation of NFIB sequences to proximal or distal sites of the MYB gene. Massive pair-end sequencing of a subset of tumors confirmed the proximal translocation to an NFIB sequence and led to the identification of a new fusion gene (NFIB-AIG1) in one of the tumors. Overall, MYB-NFIB gene fusion rate by FISH was in 52.9% whereas fusion transcript forming incidence was 38.2%. Significant statistical association between the 5' MYB transcript expression and patient survival was found. CONCLUSIONS: We conclude that: (i) t(6;9) results in complex genetic and molecular alterations in ACC, (ii) MYB-NFIB gene fusion may not always be associated with chimeric transcript formation, (iii) noncanonical MYB NFIB gene fusions occur in a subset of tumors, (iv) high MYB expression correlates with worse patient survival. PMID- 21976544 TI - Multicenter, phase II study of axitinib, a selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, in patients with metastatic melanoma. AB - PURPOSE: This multicenter, open-label, phase II study evaluated the safety and clinical activity of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, 2, and 3, in patients with metastatic melanoma. EXPERIMENTAL DESIGN: Thirty-two patients with a maximum of one prior systemic therapy received axitinib at a starting dose of 5 mg twice daily. The primary endpoint was objective response rate. RESULTS: Objective response rate was 18.8% [95% confidence interval (CI), 7.2-36.4], comprising one complete and five partial responses with a median response duration of 5.9 months (95% CI, 5.0-17.0). Stable disease at 16 weeks was noted in six patients (18.8%), with an overall clinical benefit rate of 37.5%. Six-month progression-free survival rate was 33.9%, 1-year overall survival rate was 28.1%, and median overall survival was 6.6 months (95% CI, 5.2-9.0). The most frequently (>15%) reported nonhematologic, treatment-related adverse events were fatigue, hypertension, hoarseness, and diarrhea. Treatment-related fatal bowel perforation, a known class effect, occurred in one patient. Axitinib selectively decreased plasma concentrations of soluble VEGFR (sVEGFR)-2 and sVEGFR-3 compared with soluble stem cell factor receptor (sKIT). No significant association was noted between plasma levels of axitinib and response. However, post hoc analyses indicated potential relationships between efficacy endpoints and diastolic blood pressure of 90 mm Hg or higher as well as baseline serum lactate dehydrogenase levels. CONCLUSIONS: Axitinib was well tolerated, showed a selective VEGFR inhibitory profile, and showed single-agent activity in metastatic melanoma. Further evaluations of axitinib, alone and combined with chemotherapy, are ongoing. PMID- 21976543 TI - Gene expression differences between colon and rectum tumors. AB - PURPOSE: Colorectal cancer studies typically include both colon and rectum tumors as a common entity, though this assumption is controversial and only minor differences have been reported at the molecular and epidemiologic level. We conducted a molecular study based on gene expression data of tumors from colon and rectum to assess the degree of similarity between these cancer sites at transcriptomic level. EXPERIMENTAL DESIGN: A pooled analysis of 460 colon tumors and 100 rectum tumors from four data sets belonging to three independent studies was conducted. Microsatellite instable tumors were excluded as these are known to have a different expression profile and have a preferential proximal colon location. Expression differences were assessed with linear models, and significant genes were identified using adjustment for multiple comparisons. RESULTS: Minor differences at a gene expression level were found between tumors arising in the proximal colon, distal colon, or rectum. Only several HOX genes were found to be associated with tumor location. More differences were found between proximal and distal colon than between distal colon and rectum. CONCLUSIONS: Microsatellite stable colorectal cancers do not show major transcriptomic differences for tumors arising in the colon or rectum. The small but consistent differences observed are largely driven by the HOX genes. These results may have important implications in the design and interpretation of studies in colorectal cancer. PMID- 21976546 TI - The European Medicines Agency review of pazopanib for the treatment of advanced renal cell carcinoma: summary of the scientific assessment of the Committee for Medicinal Products for Human Use. AB - On June 14, 2010, the European Commission issued a conditional marketing authorization valid throughout the European Union for pazopanib for the treatment of advanced renal cell carcinoma. Pazopanib is an antineoplastic agent that inhibits multiple receptor tyrosine kinases. The recommended oral dose is 800 mg once daily. The benefit of pazopanib is an increased progression-free survival. In the pivotal trial VEG105192, the median progression-free survival was 9.2 months (95% confidence interval, 7.4-12.9) in the pazopanib arm compared with 4.2 months (95% confidence interval, 2.8-4.2) in the placebo arm. The most common side effects include diarrhea, hair color change, hypertension, nausea, fatigue, anorexia, vomiting, dysgeusia, elevated alanine aminotransferase, elevated aspartate aminotransferase, and abdominal pain. The objective of this article is to summarize the scientific review of the application that led to approval in the European Union. PMID- 21976545 TI - Genetic variation in inflammatory pathways is related to colorectal cancer survival. AB - PURPOSE: Prognosis of patients with colorectal cancer (CRC) is associated with systemic inflammation, and anti-inflammatory drugs can reduce both CRC incidence and mortality. Genetic variation in proinflammatory pathways can affect an individual's CRC risk. However, few studies have investigated the prognostic importance of this genetic variation in CRC patients. EXPERIMENTAL DESIGN: We investigated the association between CRC survival and genetic variation in proinflammatory pathways among patients from the Puget Sound Surveillance Epidemiology and End Results registry. Single-nucleotide polymorphisms were genotyped in five genes (PTGS-1, PTGS-2, MRP4, NFkappaB, and IkappaBKbeta). Vital status was ascertained through linkage to the National Death Index. Cox proportional hazards regression was used to calculate HRs and 95% confidence intervals (CI). The false discovery rate method of Benjamini and Hochberg was applied to address multiple testing. RESULTS: Four PTGS-1 variants were associated with CRC survival. One, G>A intron 9 (rs1213266), was associated with approximately 50% lower CRC mortality (HR(AA/AG vs. GG) = 0.48; 95% CI, 0.25 0.93). Three variants, including L237M, resulted in significantly elevated CRC mortality risk, with HRs ranging from approximately 1.5 to 2.0. Two variants in IkappaBKbeta, including R526Q, were significantly associated with CRC survival. Correction for multiple testing indicated that variants in both PTGS-1 and IkappaBKbeta are reproducibly associated with CRC survival. CONCLUSION: Our findings suggest that genetic variation in proinflammatory pathways may be important for CRC prognosis. This investigation represents one of the first descriptions of the relationship between inherited polymorphisms and mortality in CRC patients and provides a starting point for further research. PMID- 21976547 TI - Biologic and clinical activity of tivozanib (AV-951, KRN-951), a selective inhibitor of VEGF receptor-1, -2, and -3 tyrosine kinases, in a 4-week-on, 2-week off schedule in patients with advanced solid tumors. AB - PURPOSE: To assess the maximum tolerated dose (MTD)/dose-limiting toxicities (DLT), safety, pharmacokinetics, and pharmacodynamics of tivozanib, a potent and selective oral VEGF receptor (VEGFR) tyrosine kinase inhibitor. EXPERIMENTAL DESIGN: Dose levels of 1.0, 1.5, and 2.0 mg/d tivozanib for 28 days followed by 14 days of medication were explored in patients with advanced solid tumors. RESULTS: Forty-one patients were enrolled. Animal data incorrectly predicted toxicity, resulting in DLTs at the starting dose (2.0 mg) consisting of grade 3 proteinuria and hypertension and grade 3 ataxia. At 1.0 mg, no DLT was observed. At an intermediate dose (1.5 mg), 1 patient experienced DLT consisting of grade 3 hypertension. This dose was determined as the MTD. Of 10 additional patients treated at 1.5 mg, 1 patient each experienced grade 3 hypertension and grade 3 fatigue, and 2 patients experienced grade 3 and 4 transaminase elevation. In 12 additional patients treated at 1.0 mg, no DLT was observed. Pharmacokinetics displayed long absorption time, dose proportional exposure, and a half-life of 4.7 days. Plasma levels of VEGF-A and soluble VEGFR-2 showed dose-dependent increases and decreases, respectively. Dynamic contrast-enhanced MRI indicated reduction in tumor perfusion. Clinical activity was observed in renal cell cancer, colorectal cancer, and other tumors. CONCLUSION: Tivozanib was well tolerated with manageable side effects. The pharmacokinetics profile revealed that tivozanib was suitable for once-daily dosing. Encouraging and durable clinical activity was observed. The recommended daily dose of tivozanib in a 4 week-on and 2-week-off dosing regimen is 1.5 mg. PMID- 21976548 TI - Heat shock protein 90 inhibitor is synergistic with JAK2 inhibitor and overcomes resistance to JAK2-TKI in human myeloproliferative neoplasm cells. AB - PURPOSE: We determined the activity of hsp90 inhibitor, and/or Janus-activated kinase 2 (JAK2) tyrosine kinase inhibitor (TKI), against JAK2-V617F-expressing cultured mouse (Ba/F3-JAK2-V617F) and human (HEL92.1.7 and UKE-1) or primary human CD34(+) myeloproliferative neoplasm (MPN) cells. EXPERIMENTAL DESIGN: Following exposure to the hsp90 inhibitor AUY922 and/or JAK2-TKI TG101209, the levels of JAK2-V617F, its downstream signaling proteins, as well as apoptosis were determined. RESULTS: Treatment with AUY922 induced proteasomal degradation and depletion of JAK2-V617F as well as attenuated the signaling proteins downstream of JAK2-V617F, that is, phospho (p)-STAT5, p-AKT, and p-ERK1/2. AUY922 treatment also induced apoptosis of HEL92.1.7, UKE-1, and Ba/F3-hJAK2-V617F cells. Combined treatment with AUY922 and TG101209 caused greater depletion of the signaling proteins than either agent alone and synergistically induced apoptosis of HEL92.1.7 and UKE-1 cells. Cotreatment with AUY922 and TG101209 also induced significantly more apoptosis of human CD34(+) MPN than normal hematopoietic progenitor cells. As compared with the sensitive controls, JAK2-TKI resistant HEL/TGR and UKE-1/TGR cells exhibited significantly higher IC(50) values for JAK2-TKI (P < 0.001), which was associated with higher expression of p JAK2, p-STAT5, p-AKT, and Bcl-xL, but reduced levels of BIM. Unlike the sensitive controls, HEL/TGR and UKE/TGR cells were collaterally sensitive to the hsp90 inhibitors AUY922 and 17-AAG, accompanied by marked reduction in p-JAK2, p-STAT5, p-AKT, and Bcl-xL, with concomitant induction of BIM. CONCLUSIONS: Findings presented here show that cotreatment with hsp90 inhibitor and JAK2-TKI exerts synergistic activity against cultured and primary MPN cells. In addition, treatment with hsp90 inhibitor may overcome resistance to JAK2-TKI in human MPN cells. PMID- 21976549 TI - Enhanced antitumor efficacy of low-dose Etoposide with oncolytic herpes simplex virus in human glioblastoma stem cell xenografts. AB - PURPOSE: Glioblastoma (GBM) inevitably recurs despite surgery, radiation, and chemotherapy. A subpopulation of tumor cells, GBM stem cells (GSC), has been implicated in this recurrence. The chemotherapeutic agent etoposide is generally reserved for treating recurrent tumors; however, its effectiveness is limited due to acute and cumulative toxicities to normal tissues. We investigate a novel combinatorial approach of low-dose etoposide with an oncolytic HSV to enhance antitumor activity and limit drug toxicity. EXPERIMENTAL DESIGN: In vitro, human GBM cell lines and GSCs were treated with etoposide alone, oncolytic herpes simplex virus (oHSV) G47Delta alone, or the combination. Cytotoxic interactions were analyzed using the Chou-Talalay method, and changes in caspase-dependent apoptosis and cell cycle were determined. In vivo, the most etoposide-resistant human GSC, BT74, was implanted intracranially and treated with either treatment alone or the combination. Analysis included effects on survival, therapy associated adverse events, and histologic detection of apoptosis. RESULTS: GSCs varied in their sensitivity to etoposide by over 50-fold in vitro, whereas their sensitivity to G47Delta was similar. Combining G47Delta with low-dose etoposide was moderately synergistic in GSCs and GBM cell lines. This combination did not enhance virus replication, but significantly increased apoptosis. In vivo, the combination of a single cycle of low-dose etoposide with G47Delta significantly extended survival of mice-bearing etoposide-insensitive intracranial human GSC derived tumors. CONCLUSIONS: The combination of low-dose etoposide with G47Delta increases survival of mice-bearing intracranial human GSC-derived tumors without adverse side effects. These results establish this as a promising combination strategy to treat resistant and recurrent GBM. PMID- 21976550 TI - Mast cells in tumor microenvironment promotes the in vivo growth of pancreatic ductal adenocarcinoma. AB - PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death. No effective therapy is currently available for PDAC because of the lack of understanding of the mechanisms leading to its growth and development. Inflammatory cells, particularly mast cells, have been shown to play key roles in some cancers. We carried out this study to test the hypothesis that mast cells in the tumor microenvironment are essential for PDAC tumorigenesis. EXPERIMENTAL DESIGN: The presence of inflammatory cells at various stages of PDAC development was determined in a spontaneous mouse model of PDAC (K-ras(G12V)). The importance of mast cells was determined using orthotopically implanted PDAC cells in mast cell-deficient Kit(w-sh/w-sh) mice and further confirmed by reconstitution of wild-type bone marrow-derived mast cells. Clinical relevance was assessed by correlating the presence of mast cells with clinical outcome in patients with PDAC. RESULTS: In the spontaneous mouse model of PDAC (K-ras(G12V)), there was an early influx of mast cells to the tumor microenvironment. PDAC tumor growth was suppressed in mast cell-deficient Kit(w-sh/w-sh) mice, but aggressive PDAC growth was restored when PDAC cells were injected into mast cell-deficient mice reconstituted with wild-type bone marrow-derived mast cells. Mast cell infiltration into the tumor microenvironment was predictive of poor prognosis in patients with PDAC. CONCLUSIONS: Mast cells play an important role in PDAC growth and development in mouse models and are indicative of poor prognosis in humans, which makes them a potential novel therapeutic target. PMID- 21976551 TI - Improved monitoring of differences in serial laboratory results. PMID- 21976552 TI - High-sensitivity cardiac troponin assays--change is important. PMID- 21976553 TI - Thousands of lesions in disseminated cysticercosis. PMID- 21976554 TI - Malaria in Africa can be eliminated. AB - A concerted effort to control malaria in Africa has produced dramatic reductions in childhood death in the past decade. This early success has prompted the global community to commit to eradication of malaria deaths and eventually all transmission. Evidence suggests that this is a feasible goal using currently available interventions, augmented with newer tools such as vaccines, which are in development. Malaria deaths are entirely preventable now, and our sustained political and financial commitment to continue to prevent these deaths hangs in the balance. PMID- 21976555 TI - Dramatic decrease in malaria transmission after large-scale indoor residual spraying with bendiocarb in Benin, an area of high resistance of Anopheles gambiae to pyrethroids. AB - In 2008, the National Malaria Control Program in Benin implemented a vector control intervention based on indoor residual spraying (IRS). Four districts of high resistance of Anopheles gambiae to pyrethroids were sprayed with bendiocarb. More than 350,000 inhabitants have been protected. Entomologic parameters in the control area were compared with those in intervention sites. The study has shown a drastic decrease in the An. gambiae biting rate in the sprayed areas. Results of an enzyme-linked immunosorbent assay were negative for Plasmodium falciparum antigen during the entire period of the intervention. No household members received infected bites (entomologic inoculation rate = 0 during January-July). Parous rates were low in areas covered by IRS because bendiocarb is not conducive to long-term mosquito survival. Bendiocarb was found to be a good alternative insecticide for IRS in Benin, in areas where An. gambiae has developed high resistance to pyrethroids. PMID- 21976556 TI - Evaluation of loop-mediated isothermal amplification (LAMP) for malaria diagnosis in a field setting. AB - We used the loop-mediated isothermal amplification (LAMP) method developed by our group for malaria diagnosis with genus-specific and species-specific primers for the four human malaria parasites at a field clinic in comparison with standard microscopy. Among 110 blood samples collected from the malaria clinic in Thailand, LAMP detected 59 of 60 samples positive by microscopy (sensitivity = 98.3%) and none of the 50 microscopy-negative samples (specificity = 100%). Negative predictive value (NPV) and positive predictive value (PPV) of LAMP were 98% and 100%, respectively. These results indicate that LAMP is an effective tool for malaria diagnosis at a field clinic in a field setting. PMID- 21976557 TI - A reversal in reductions of child mortality in western Kenya, 2003-2009. AB - We report and explore changes in child mortality in a rural area of Kenya during 2003-2009, when major public health interventions were scaled-up. Mortality ratios and rates were calculated by using the Kenya Medical Research Institute/Centers for Disease Control and Prevention Demographic Surveillance System. Inpatient and outpatient morbidity and mortality, and verbal autopsy data were analyzed. Mortality ratios for children less than five years of age decreased from 241 to 137 deaths/1,000 live-births in 2003 and 2007 respectively. In 2008, they increased to 212 deaths/1,000 live-births. Mortality remained elevated during the first 8 months of 2009 compared with 2006 and 2007. Malaria and/or anemia accounted for the greatest increases in child mortality. Stock-outs of essential antimalarial drugs during a time of increased malaria transmission and disruption of services during civil unrest may have contributed to increased mortality in 2008-2009. To maintain gains in child survival, implementation of good policies and effective interventions must be complemented by reliable supply and access to clinical services and essential drugs. PMID- 21976558 TI - Role of Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes on in vitro chloroquine resistance in isolates of Plasmodium falciparum from Thailand. AB - Resistance to chloroquine is a public health problem worldwide. Polymorphisms of the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes have been linked to chloroquine resistance. Although the K76T mutation in the pfcrt gene has been shown to be a key determinant in chloroquine resistance, evidence suggests that the pfmdr1 gene could modulate the level of chloroquine resistance. However, few studies of field isolates could identify the interactive role of these two genes in chloroquine resistance. Thus, we evaluated the influence of pfcrt and pfmdr1 polymorphisms on in vitro chloroquine sensitivity in 89 adapted isolates of P. falciparum from Thailand. We found that 87 of 89 isolates contained the CVIET haplotype of the pfcrt gene. Two additional mutations in the pfcrt gene were identified, i.e., K6Q and H97L. For the pfmdr1 polymorphisms, the 184F allele was common in the parasites isolated along the Thailand-Cambodia border, and those isolated along the Thailand-Myanmar border contained higher copy numbers. Our results indicate that the additional mutations, in particular H97L in the pfcrt gene and Y184F in the pfmdr1 gene and its copy number, influence the level of chloroquine resistance. PMID- 21976559 TI - Presumptive treatment to reduce imported malaria among refugees from east Africa resettling in the United States. AB - During May 4, 2007-February 29, 2008, the United States resettled 6,159 refugees from Tanzania. Refugees received pre-departure antimalarial treatment with sulfadoxine-pyrimethamine (SP), partially supervised (three/six doses) artemether lumefantrine (AL), or fully supervised AL. Thirty-nine malaria cases were detected. Disease incidence was 15.5/1,000 in the SP group and 3.2/1,000 in the partially supervised AL group (relative change = -79%, 95% confidence interval = 56% to -90%). Incidence was 1.3/1,000 refugees in the fully supervised AL group (relative change = -92% compared with SP group; 95% confidence interval = -66% to -98%). Among 39 cases, 28 (72%) were in refugees < 15 years of age. Time between arrival and symptom onset (median = 14 days, range = 3-46 days) did not differ by group. Thirty-two (82%) persons were hospitalized, 4 (10%) had severe manifestations, and 9 (27%) had parasitemias > 5% (range = < 0.1-18%). Pre departure presumptive treatment with an effective drug is associated with decreased disease among refugees. PMID- 21976560 TI - HMS-related hemolysis after acute attacks of Plasmodium vivax malaria. AB - Among a cohort of 1,213 cases treated for Plasmodium vivax malaria from an isolated Papua New Guinean population, seven adults with severe and sustained hemolytic anemia after clearance of the peripheral parasitemia were prospectively investigated. All the patients fulfilled the criteria for hyper-reactive malarial splenomegaly and in 2 of 7 cases an IgG warm antibody was identified. Hereditary hemolytic anemia was excluded in 5 of 5 patients. All treated cases improved after an initial high dose of prednisone and antimalarial chemoprophylaxis. The persistence of marked anemia in a patient with splenomegaly after a P. vivax attack should raise the suspicion of hyper-reactive malarial splenomegaly. PMID- 21976561 TI - Hematologic parameters in pediatric uncomplicated Plasmodium falciparum malaria in sub-Saharan Africa. AB - Hematologic changes in acute and convalescent uncomplicated Plasmodium falciparum malaria have not been well studied, particularly in young children in Africa. Hematologic data were obtained for 3,044 children less than five years of age in seven randomized controlled trials at 14 sites. Using paired analysis between day 28 and baseline in patients without parasitologic failure as a proxy for malaria induced effects, we found a statistically significant but clinically modest increase in leukocyte counts (5%) resulting from a larger increase in neutrophils (43%) than the decrease in lymphocytes counts (-16%); levels of hemoglobin and platelets decreased (-13% and -49%, respectively). Multivariate random effects analysis showed trends during follow-up (increased levels of hemoglobin, platelets and lymphocytes, and decreased levels of leukocytes and neutrophils) and identified explanatory variables. The risk of neutropenia increased with follow-up time independent of treatment outcome, and was lower with age, higher baseline parasitemia, and artemisinin combination treatment. These analyses provides information on hematologic variations caused by malaria. PMID- 21976562 TI - Distinguishing malaria from severe pneumonia among hospitalized children who fulfilled integrated management of childhood illness criteria for both diseases: a hospital-based study in Mozambique. AB - Malaria and severe pneumonia in hospitalized young children may show striking clinical similarities, making differential diagnosis challenging. We investigated ways to increase diagnostic accuracy in patients hospitalized with clinical symptoms compatible with malaria and severe pneumonia, in an area with high a prevalence of infection with human immunodeficiency virus. A total of 646 children admitted at the Manhica District Hospital in Manhica, Mozambique who met the World Health Organization clinical criteria for severe pneumonia and malaria were recruited for 12 months and thoroughly investigated to ascertain an accurate diagnosis. Although symptom overlap between malaria and severe pneumonia was frequent among hospitalized children, true disease overlap was uncommon. Clinical presentation and laboratory determinations were ineffective in reliably distinguishing between the two diseases. Infection with human immunodeficiency virus differentially influenced the epidemiology and clinical presentation of these two infectious diseases, further challenging their discrimination on clinical grounds, and having a greater impact on the current burden and prognosis of severe pneumonia. PMID- 21976563 TI - Identification and phylogenetic analysis of Japanese Macaque Babesia-1 (JM-1) detected from a Japanese Macaque (Macaca fuscata fuscata). AB - We demonstrate here the identification and phylogenetic characterization of Babesia microti (B. microti)-like parasite detected from a splenectomized Japanese macaque (Macaca fuscata fuscata) at a facility for laboratory animal science. On Day 133 after splenectomy, intra-erythrocytic parasites were found on light microscopic examination, and the level of parasitemia reached 0.3% on blood smear. Molecular characterization of the parasite using nested-polymerization chain reactions targeting the 18S rRNA, beta-tubulin, and subunit 7 (eta) of the chaperonin-containing t-complex polypeptide 1 (CCT7) genes were identified as a B. microti-like parasite, designated the Japanese Macaque Babesia-1 (JM-1). PMID- 21976564 TI - Effect of human urine on cell cycle and infectivity of Leismania species promastigotes in vitro. AB - In vitro cultivation of Leishmania parasites plays an important role in diagnosis and treatment of leishmaniasis and in vaccine and drug development studies. Conversely, long-term cultivation of Leishmania parasites usually results in decreased infectivity potential. Some studies reported a stimulatory effect of human urine in Leishmania promastigotes. However, there is no information about the effects of urine within culture on the infectivity of Leishmania parasites. Analysis of the effect of urine have showed that proliferation indexes were significantly increased in culture medium supplemented with human urine (L. tropica = 38.17 +/- 5.12, L. donovani = 34.74 +/- 5.6, L. major = 34.22 +/- 4.66, and L. infantum 35.88 +/- 6.40) than in controls. Infection indexes were 13 +/- 1.7 for L. tropica, 55 +/- 2.2 for L. infantum, 41 +/- 3.14 for L. donovani, and 49 +/- 3.26 for L. major. Our results showed that human urine increased the infectivity and proliferation of Leishmania parasites. PMID- 21976565 TI - First report on Ambisome-associated allergic reaction in two Sudanese leishmaniasis patients. AB - Post kala-azar dermal leishmaniasis (PKDL) and mucosal leishmaniasis (ML) are serious clinical forms of leishmaniasis caused by Leishmania donovani parasites in Sudan. Although pentavalent antimonys are used as the first line of treatment of all clinical forms of leishmaniasis, persistent PKDL and ML patients are treated with liposomal amphotericin B (Ambisome) as a second-line drug. In this work, we report the development of allergic reactions by a PKDL and a ML Sudanese patient to Ambisome. The findings warrant future close supervision of patients to be treated with the drug. PMID- 21976566 TI - First report on natural infection of Phlebotomus sergenti with Leishmania promastigotes in the cutaneous leishmaniasis focus in southeastern Tunisia. AB - During September 2010, 133 female sand flies were caught inside houses of patients with cutaneous leishmaniasis in the focus for this disease in southeastern Tunisia and subsequently dissected. One specimen was positive for Leishmania protozoa. This sand fly species was identified as Phlebotomus sergenti, and the parasite was identified as L. tropica. This is the first report of P. sergenti involvement in transmission of L. tropica in Tunisia. PMID- 21976567 TI - Feeding and defecation behavior of Triatoma rubida (Uhler, 1894) (Hemiptera: Reduviidae) under laboratory conditions, and its potential role as a vector of Chagas disease in Arizona, USA. AB - Chagas disease is caused by the parasite Trypanosoma cruzi, which is transmitted to humans by blood-sucking triatomine insects. This disease is endemic throughout Mexico and Central and South America, but only a few autochthonous cases have been reported in the United States, despite the fact that infected insects readily invade houses and feed on humans. Competent vectors defecate during or shortly after feeding so that infective feces contact the host. We thus studied the feeding and defecation behaviors of the prevalent species in southern Arizona, Triatoma rubida. We found that whereas defecation during feeding was frequent in females (93%), it was very rare in immature stages (3%), and absent in males. Furthermore, more than half of the immature insects that exhibited multiple feeding bouts (62%) defecated during interruptions of feeding, i.e., while likely on or near the host. These results indicate that T. rubida potentially could transmit T. cruzi to humans. PMID- 21976568 TI - Investigation of potential zoonotic transmission of cryptosporidiosis in southern India. AB - The common species and subgenotypes causing cryptosporidiosis were studied in 394 children and 627 animals with diarrhea in Vellore in southern India. Although no zoonotic strains were identified in 13 infected children, 1 of 12 infected animals had C. hominis, indicating the potential for cross-species transmission. This study also reports C. xiaoi for the first time in India. PMID- 21976569 TI - Seroprevalence and sources of toxoplasmosis among Orang Asli (indigenous) communities in Peninsular Malaysia. AB - This study aims to evaluate the current seroprevalence of toxoplasmosis among indigenous communities in Peninsular Malaysia and relate its association with epidemiological data. Overall seroprevalence of Toxoplasma gondii was 37.0% with 31.0% immunoglobulin (Ig) G, 1.8% IgM, and 4.2% seropositivity for both anti Toxoplasma antibodies. Multivariate analysis showed that age above 12 years (odds ratio [OR] = 2.70, 95% confidence interval [CI] = 1.75-4.04, P < 0.001), using untreated river and mountain water supplies (OR = 1.50, 95% CI = 1.01-2.40, P = 0.050), and close proximity with cats (OR = 1.40, 95% CI = 1.10-1.76, P = 0.010) were factors associated with toxoplasmosis. Given the high seroprevalence of toxoplasmosis among these communities who live in poor socioeconomic conditions, a comprehensive health surveillance program and screening should be initiated among women of childbearing age and pregnant women during the antenatal period for early diagnosis and treatment. The role of domestic cats and environmental contamination with oocyst in soil and water has to be highlighted and addressed in future prevention strategies for these communities. PMID- 21976570 TI - Murine models of vaginal trichomonad infections. AB - Trichomonas vaginalis and Tritrichomonas foetus cause common sexually transmitted infections in humans and cattle, respectively. Mouse models of trichomoniasis are important for pathogenic and therapeutic studies. Here, we compared murine genital infections with T. vaginalis and T. foetus. Persistent vaginal infection with T. foetus was established with 100 parasites but T. vaginalis infection required doses of 10(6), perhaps because of greater susceptibility to killing by mouse vaginal polymorphonuclear leukocytes. Infection with T. vaginalis persisted longest after combined treatment of mice with estrogen and dexamethasone, whereas infection was only short-lived when mice were given estrogen or dexamethasone alone, co-infected with Lactobacillus acidophilus, and/or pretreated with antibiotics. Infection rates were similar with metronidazole-resistant (MR) and metronidazole-sensitive (MS) T. vaginalis. High dose but not low dose metronidazole treatment controlled infection with MS better than MR T. vaginalis. These murine models will be valuable for investigating the pathogenesis and treatment of trichomoniasis. PMID- 21976571 TI - Human antibody response to thioredoxin peroxidase-1 and tandem repeat proteins as immunodiagnostic antigen candidates for Schistosoma japonicum infection. AB - Schistosomiasis continues to be a public health problem in many tropical and subtropical countries. Improving the diagnostic tools for surveillance and monitoring in areas that have reached elimination level will help hasten the possible elimination of this disease. This study therefore aims to develop enzyme linked immunosorbent assay through the use of recombinant proteins such as thioredoxin peroxidase-1 (SjTPx-1) and four tandem repeat proteins (Sj1TR, Sj2TR, Sj4TR, and Sj7TR). Cutoff values were calculated using 38 serum samples from healthy Japanese volunteers. Sera from 35 schistosomiasis-confirmed patients, four cured from the disease by chemotherapy, and 15 endemic negative controls were used to assess these antigens. SjTPx-1 and Sj7TR both had 85.71% sensitivity. Furthermore, these antigens were also tested against human sera positive for other parasitic infections and showed no or very minimal cross reaction. These results suggest the potential defined antigens for development of an accurate diagnostic test for schistosomiasis. PMID- 21976572 TI - Soil-transmitted Helminthiasis in the United States: a systematic review--1940 2010. AB - The epidemiology of soil-transmitted helminth infections (hookworm, Trichuris trichiura, Ascaris lumbricoides, and Strongyloides stercoralis) in the United States is poorly understood. To gain understanding of the status of disease, a systematic review was performed to assess the prevalence of soil-transmitted helminth infections in the United States. Of all studies reviewed, 14 were designated as high-quality. High-quality studies were published from 1942 to 1982 and showed that infection was prevalent throughout the southern United States and Appalachia as recently as 1982, finding that hookworm (19.6%), T. trichiura (55.2%), A. lumbricoides (49.4%), and S. stercoralis (3.8%) affected significant percentages of the population. However, because the most recent high-quality studies were published over 25 years ago, the literature does not provide sufficient data to assess current endemic transmission. Because the status of disease remains unclear, there is a need for additional studies to determine if soil-transmitted helminths remain endemic in the United States. PMID- 21976573 TI - Eosinophilic meningitis attributable to Angiostrongylus cantonensis infection in Hawaii: clinical characteristics and potential exposures. AB - The most common infectious cause of eosinophilic meningitis is Angiostrongylus cantonensis, which is transmitted largely by consumption of snails/slugs. We previously identified cases of angiostrongyliasis that occurred in Hawaii from 2001 to 2005; the highest incidence was on the island of Hawaii. We now report symptoms, laboratory parameters, and exposures. Eighteen patients were evaluated; 94% had headache, and 65% had sensory symptoms (paresthesia, hyperesthesia, and/or numbness). These symptoms lasted a median of 17 and 55 days, respectively. Three persons recalled finding a slug in their food/drink. Case-patients on the island of Hawaii were more likely than case-patients on other islands to consume raw homegrown produce in a typical week (89% versus 0%, P < 0.001) and to see snails/slugs on produce (56% versus 0%, P = 0.03). Residents and travelers should be aware of the potential risks of eating uncooked produce in Hawaii, especially if it is from the island of Hawaii and locally grown. PMID- 21976574 TI - Association of mass treatment with azithromycin in trachoma-endemic communities with short-term reduced risk of diarrhea in young children. AB - A cohort study was designed to assess the impact of mass distribution of azithromycin (MDA) for trachoma control on incidence over six months of pediatric diarrhea in eight communities in rural Tanzania. A single dose of azithromycin was offered to all residents in four communities, where trachoma prevalence was >= 10%. Four geographically matched communities had trachoma prevalences < 10% and did not receive MDA. All randomly selected children (n = 1036) were followed up for six months post-MDA with bi-weekly surveillance at home. In the 0-1-month and 1-3-month periods, MDA exposure was associated with a 39% (rate ratio = 0.61, 95% confidence interval = 0.39-0.95) and 24% (rate ratio = 0.76, 95% confidence interval = 0.54-1.07) lower risk of diarrhea, respectively, compared with those unexposed, after adjustment for clustering and covariates. By the 3-6-month period, diarrhea incidence was comparable between groups. Thus, MDA was associated with a short-term reduction in diarrheal morbidity in children. PMID- 21976575 TI - Aggregate evaluable organ dysfunction predicts in-hospital mortality from sepsis in Uganda. AB - We evaluated the association between severity of sepsis and in-hospital mortality in 150 patients with non-surgical sepsis at a regional referral hospital in Uganda. In-hospital mortality occurred in 5 of 52 (9.6%) patients with sepsis, 24 of 71 (33.8%) patients with severe sepsis, and 16 of 27 (59.3%) patients with septic shock. In the multivariate analysis, the identification of severe sepsis (adjusted hazard ratio [AHR] = 2.9, 95% confidence interval [CI] = 1.0-8.2, P = 0.04), septic shock (AHR = 5.7, 95% CI = 1.6-20.3, P = 0.007), and dysfunction of three or more organs (AHR = 2.9, 95% CI = 1.1-7.3, P = 0.03) increased the risk of in-hospital mortality. Adding aggregate organ dysfunction to the multivariate equation that included the sepsis category statistically significantly improved the model, but the opposite did not. Predictors of mortality were easily measurable and could be used to risk stratify critically ill patients in resource constrained settings. PMID- 21976576 TI - Acute post-streptococcal glomerulonephritis in the Northern Territory of Australia: a review of 16 years data and comparison with the literature. AB - Data relating to acute post-streptococcal glomerulonephritis (APSGN) from the notifiable diseases surveillance system in the Northern Territory of Australia was extracted and analyzed. Isolates of Streptococcus pyogenes from confirmed cases were emm sequence typed. From 1991 to July 2008, there were 415 confirmed cases and 23 probable cases of APSGN notified. Four hundred fifteen (94.7%) of these were Indigenous Australians and 428 (97.7%) were people living in remote or very remote locations. The median age of cases was 7 years (range 0-54). The incidence of confirmed cases was 12.5/100,000 person-years, with an incidence in Indigenous Australian children younger than 15 years of age of 94.3 cases/100,000 person-years. The overall rate ratio of confirmed cases in Indigenous Australians to non-Indigenous Australians was 53.6 (95% confidence interval 32.6-94.8). Outbreaks of disease across multiple communities occurred in 1995 (N = 68), 2000 (N = 55), and 2005 (N = 87 [confirmed cases]). Various emm types of S. pyogenes were isolated from cases of APSGN including some types not previously recognized to be nephritogenic. The widespread outbreak in 2005 was caused by emm55.0 S. pyogenes. Acute post-streptococcal glomerulonephritis continues to occur in remote Indigenous communities in Australia at rates comparable to or higher than those estimated in developing countries. Improvements in preventative and outbreak control strategies are needed. PMID- 21976577 TI - Vernal keratoconjunctivitis in school children in Rwanda and its association with socio-economic status: a population-based survey. AB - Vernal keratoconjunctivitis (VKC) is an allergic eye disease and an important cause of hospital referral among children in Africa and Asia. Hospital-based studies have suggested a role for parasites in its pathogenesis. To determine the prevalence and risk factors for VKC in Central Africa, we conducted a nested population-based case control study in Rwanda, involving randomly selected primary schools from different environments (rural/urban) and climate. A prevalence of VKC of 4.0% (95% confidence interval 3.3-4.7%) was found among 3,041 children studied (participation rate 94.7%). The intestinal parasitic burden was not related to VKC. Besides hot dry climate (odds ratio [OR] = 1.5, P = 0.05) and male gender (OR = 1.7, P = 0.005), multivariate analysis identified higher economic status as a risk for VKC (OR = 1.4, P = 0.005). The effect on VKC of higher economic status appears not to act through differences in parasitic intestinal load. PMID- 21976578 TI - Infection prevalences of common tick-borne pathogens in adult lone star ticks (Amblyomma americanum) and American dog ticks (Dermacentor variabilis) in Kentucky. AB - Rocky Mountain spotted fever, Lyme disease, and ehrlichiosis are tick-borne diseases that are reported annually in Kentucky. We conducted a survey to describe infection prevalence of tick-borne pathogens in Amblyomma americanum and Dermacentor variabilis ticks collected in Kentucky. During 2007-2008, we collected 287 ticks (179 D. variabilis and 108 A. americanum) from canine, feral hog, horse, raccoon, white-tailed deer, and human hosts in six counties in Kentucky. Ticks were screened for Rickettsia spp., Borrelia spp., and Ehrlichia spp. by using polymerase chain reaction. Forty-one (14.3%) ticks (31 A. americanum and 10 D. variabilis) were polymerase chain reaction-positive for a Rickettsia spp. Fourteen (4.9%) ticks (6 A. americanum and 8 D. variabilis) were positive for E. chaffeensis, and 4 A. americanum (1.4%) were positive for E. ewingii. One (0.4%) A. americanum was positive for Borrelia lonestari. Although Rocky Mountain spotted fever is diagnosed in Kentucky, no R. rickettsii was found in ticks in this study. PMID- 21976579 TI - Priming effect of dengue and yellow fever vaccination on the immunogenicity, infectivity, and safety of a tetravalent dengue vaccine in humans. AB - A dengue vaccine effective against all four serotypes is urgently needed. However, safety and immunogenicity could be affected by prior exposure to flaviviruses. This open, controlled, phase IIa study was conducted in 35 healthy adults who had received monovalent, live attenuated Vero cell-derived dengue vaccine against dengue virus 1 (VDV1) or 2 (VDV2) or yellow fever (YF) vaccine 1 year before or who were flavivirus-naive. All participants received one subcutaneous injection of tetravalent dengue vaccine (TDV) and were followed for 180 days. Previous vaccination did not increase reactogenicity, laboratory abnormalities, or incidence of vaccine viremia, but it did increase the neutralizing antibody response to dengue virus that persisted at day 180. There was no increase in YF antibodies in participants previously immunized with YF vaccine. Prior exposure to YF or monovalent dengue vaccines had no adverse effects on the safety or incidence of viremia associated with this TDV, but it increased immunogenicity. PMID- 21976580 TI - Quality of life among adults with confirmed dengue in Brazil. AB - The main objective of this study was to measure the quality of life (QoL) during a dengue episode. We conducted a facility-based survey in central Brazil in 2005 and recruited 372 laboratory-confirmed dengue patients greater than 12 years of age in hospital and ambulatory settings. We administered the World Health Organization QoL instrument approximately 15 days after the onset of symptoms. We used principal component analysis with varimax rotation to identify domains related to QoL. The median age of interviewees was 36 years. Most (85%) reported their general health status as very good or good before the dengue episode. Although ambulatory patients were mainly classified as having dengue fever, 44.8% of hospitalized patients had dengue hemorrhagic fever or intermediate dengue. Principal component analysis identified five principal components related to cognition, sleep and energy, mobility, self-care, pain, and discomfort, which explained 73% of the variability of the data matrix. Hospitalized patients had significantly lower mean scores for dimensions cognition, self-care, and pain than ambulatory patients. This investigation documented the generally poor QoL during a dengue episode caused by the large number of domains affected and significant differences between health care settings. PMID- 21976581 TI - Description of a prospective 17DD yellow fever vaccine cohort in Recife, Brazil. AB - From September 2005 to March 2007, 238 individuals being vaccinated for the first time with the yellow fever (YF) -17DD vaccine were enrolled in a cohort established in Recife, Brazil. A prospective study indicated that, after immunization, anti-YF immunoglobulin M (IgM) and anti-YF IgG were present in 70.6% (IgM) and 98.3% (IgG) of the vaccinated subjects. All vaccinees developed protective immunity, which was detected by the plaque reduction neutralization test (PRNT) with a geometric mean titer of 892. Of the 238 individuals, 86.6% had IgG antibodies to dengue virus; however, the presence of anti-dengue IgG did not interfere significantly with the development of anti-YF neutralizing antibodies. In a separate retrospective study of individuals immunized with the 17DD vaccine, the PRNT values at 5 and 10 years post-vaccination remained positive but showed a significant decrease in neutralization titer (25% with PRNT titers < 100 after 5 years and 35% after 10 years). PMID- 21976582 TI - Yellow fever vaccine seroconversion in travelers. AB - To assess immunity after yellow fever (YF) 17D live-attenuated vaccination, we measured the antibody levels before vaccination and at 21 days and 8 months after vaccination in YF-naive travelers. Thirty subjects were enrolled in the study, with 100% providing sera at 21 days and 86.6% providing sera at 8 months. All subjects seroconverted by day 21, and the geometric mean titers of the anti-YF antibodies decreased between day 21 and month 8 from 6,451 to 1,246. This study corroborates the high rates of seroconversion achieved by the live-attenuated YF vaccine. PMID- 21976583 TI - Experimental transmission of Mayaro virus by Aedes aegypti. AB - Outbreaks of Mayaro fever have been associated with a sylvatic cycle of Mayaro virus (MAYV) transmission in South America. To evaluate the potential for a common urban mosquito to transmit MAYV, laboratory vector competence studies were performed with Aedes aegypti from Iquitos, Peru. Oral infection in Ae. aegypti ranged from 0% (0/31) to 84% (31/37), with blood meal virus titers between 3.4 log(10) and 7.3 log(10) plaque-forming units (PFU)/mL. Transmission of MAYV by 70% (21/30) of infected mosquitoes was shown by saliva collection and exposure to suckling mice. Amount of viral RNA in febrile humans, determined by real-time polymerase chain reaction, ranged from 2.7 to 5.3 log(10) PFU equivalents/mL. Oral susceptibility of Ae. aegypti to MAYV at titers encountered in viremic humans may limit opportunities to initiate an urban cycle; however, transmission of MAYV by Ae. aegypti shows the vector competence of this species and suggests potential for urban transmission. PMID- 21976584 TI - Reduced avian virulence and viremia of West Nile virus isolates from Mexico and Texas. AB - A West Nile virus (WNV) isolate from Mexico (TM171-03) and BIRD1153, a unique genotype from Texas, have exhibited reduced murine neuroinvasive phenotypes. To determine if murine neuroinvasive capacity equates to avian virulence potential, American crow (Corvus brachyrhynchos) and house sparrows (Passer domesticus) were experimentally inoculated with representative murine neuroinvasive/non neuroinvasive strains. In both avian species, a plaque variant from Mexico that was E-glycosylation competent produced higher viremias than an E-glycosylation incompetent variant, indicating the potential importance of E-glycosylation for avian replication. The murine non-neuroinvasive BIRD1153 strain was significantly attenuated in American crows but not house sparrows when compared with the murine neuroinvasive Texas strain. Despite the loss of murine neuroinvasive properties of nonglycosylated variants from Mexico, our data indicate avian replication potential of these strains and that unique WNV virulence characteristics exist between murine and avian models. The implications of reduced avian replication of variants from Mexico for restricted WNV transmission in Latin America is discussed. PMID- 21976585 TI - The emergence of rotavirus G12 and the prevalence of enteric viruses in hospitalized pediatric diarrheal patients in southern Vietnam. AB - Diarrhea is a major cause of childhood morbidity and mortality in developing countries, and the majority of infections are of viral etiology. We aimed to compare the etiological prevalence of the major enteric viruses in an urban and a rural setting in southern Vietnam. We simultaneously screened fecal specimens from 362 children in Ho Chi Minh City and Dong Thap province that were hospitalized with acute diarrhea over a 1-month-long period for four viral gastrointestinal pathogens. Rotavirus was the most common pathogen identified, but there was a differential prevalence of rotavirus and norovirus between the urban and rural locations. Furthermore, rotavirus genotyping and phylogenetic analysis again differentiated the genotypes by the sampling location. Our data show a disproportional distribution of enteric viral pathogens in urban and rural locations, and we provide evidence of continual importation of new rotavirus strains into southern Vietnam and report the emergence of rotavirus genotype G12. PMID- 21976586 TI - Alterations in T cell subsets in human immunodeficiency virus-infected adults with co-infections in southern Mozambique. AB - T cell activation and depletion of naive T cells are hallmarks of human immunodeficiency virus (HIV) pathogenesis. This study explored the relationships between certain co-infections (including syphilis, hepatitis B and C, human T cell lymphotrophic viruses I and II [HTLV-I/II], Kaposi sarcoma-associated herpesvirus [KSHV], Plasmodium falciparum malaria, and tuberculosis), and levels of activated CD8 and CD4 T cell subsets as well as naive and memory CD4 T cells in HIV-infected adults in a rural area of southern Mozambique. We found that syphilis infection and to a lesser extent HTLV-I/II seropositivity were independently associated with higher CD8 T cell activation (CD8+ CD38+ HLA-DR+) whereas only syphilis was associated with higher CD4 T cell activation. Furthermore, KSHV and HTLV-I/II seropositivities were independently associated with a lower percentage of naive CD4 T cells (CD4+ CD45RA+ CD62L+). These results highlight the importance of screening and prompt treatment of syphilis, and raise questions as to whether HIV-positive persons with certain chronic viral co infections should initiate combined antiretroviral therapy at higher CD4 cell counts. PMID- 21976587 TI - Neuropsychiatric and socioeconomic status impact antiretroviral adherence and mortality in rural Zambia. AB - We conducted a prospective cohort study of 496 adults starting antiretroviral treatment (ART) to determine the impact of neuropsychiatric symptoms and socioeconomic status on adherence and mortality. Almost 60% had good adherence based upon pharmacy records. Poor adherence was associated with being divorced, poorer, food insecure, and less educated. Longer travel time to clinic, concealing one's human immunodeficiency virus (HIV) status, and experiencing side effects predicted poor adherence. Over a third of the patients had cognitive impairment and poorer cognitive function was also associated with poor adherence. During follow-up (mean 275 days), 20% died-usually within 90 days of starting ART. Neuropsychiatric symptoms, advanced HIV, peripheral neuropathy symptoms, food insecurity, and poverty were associated with death. Neuropsychiatric symptoms, advanced HIV, and poverty remained significant independent predictors of death in a multivariate model adjusting for other significant factors. Social, economic, cognitive, and psychiatric problems impact adherence and survival for people receiving ART in rural Zambia. PMID- 21976590 TI - International Committee on Systematics of Prokaryotes. Subcommittee on the taxonomy of Campylobacter and related bacteria: Minutes of the closed Meeting, 2 September 2009, Niigata, Japan. PMID- 21976591 TI - Directory information. PMID- 21976592 TI - Membership list as of July 1, 2011. PMID- 21976594 TI - Electrical slow waves in the mouse oviduct are dependent upon a calcium activated chloride conductance encoded by Tmem16a. AB - Myosalpinx contractions are critical for oocyte transport along the oviduct. A specialized population of pacemaker cells-oviduct interstitial cells of Cajal generate slow waves, the electrical events underlying myosalpinx contractions. The ionic basis of oviduct pacemaker activity is unknown. We examined the role of a new class of Ca(2+)-activated Cl(-) channels (CaCCs)-anoctamin 1, encoded by Tmem16a-in oviduct slow wave generation. RT-PCR revealed the transcriptional expression of Tmem16a-encoded CaCCs in the myosalpinx. Intracellular microelectrode recordings were performed in the presence of two pharmacologically distinct Cl(-) channel antagonists, anthracene-9-carboxylic acid and niflumic acid. Both of these inhibitors caused membrane hyperpolarization, reduced the duration of slow waves, and ultimately inhibited pacemaker activity. Niflumic acid also inhibited propagating calcium waves within the myosalpinx. Slow waves were present at birth in wild-type and heterozygous oviducts but failed to develop by birth in mice homozygous for a null allele of Tmem16a (Tmem16a(tm1Bdh/tm1Bdh)). These data suggest that Tmem16a-encoded CaCCs contribute to membrane potential and are responsible for the upstroke and plateau phases of oviduct slow waves. PMID- 21976595 TI - Expression of structural proteins in human female and male genital epithelia and implications for sexually transmitted infections. AB - Men and women differ in their susceptibility to sexually transmittable infections (STIs) such as human immunodeficiency virus (HIV). However, a paucity of published information regarding the tissue structure of the human genital tract has limited our understanding of these gender differences. We collected cervical, vaginal, and penile tissues from human adult donors. Tissues were prepared with hematoxylin and eosin stains or immunofluorescence labeling of epithelial cell proteins and were analyzed for structural characteristics. Rhesus macaque genital tissues were evaluated to assess the use of this model for HIV/simian immunodeficiency virus transmission events. We found the stratified squamous epithelia of the male and female genital tract shared many similarities and important distinctions. Expression of E-cadherins, desmogleins 1/2, and involucrin was seen in all squamous epithelia, though expression patterns were heterogeneous. Filaggrin and a true cornified layer were markedly absent in female tissues but were clearly seen in all male epithelia. Desmogleins 1/2 were more consistent in the outermost strata of female squamous genital epithelia. Macaque tissues were similar to their respective human tissues. These initial observations highlight how male and female genital epithelia resemble and differ from one another. Further information regarding tissue structural characteristics will help to understand how STIs traverse these barriers to cause infection. This knowledge will be essential in future HIV pathogenesis, transmission, and prevention studies. PMID- 21976596 TI - Origins of granulosa cells clarified and complexified by waves. AB - Temporal differences in granulosa cell specification in the ovary reflect distinct follicle fates by Mork et al: a commentary. PMID- 21976597 TI - Temporal differences in granulosa cell specification in the ovary reflect distinct follicle fates in mice. AB - The embryonic origins of ovarian granulosa cells have been a subject of debate for decades. By tamoxifen-induced lineage tracing of Foxl2-expressing cells, we show that descendants of the bipotential supporting cell precursors in the early gonad contribute granulosa cells to a specific population of follicles in the medulla of the ovary that begin to grow immediately after birth. These precursor cells arise from the proliferative ovarian surface epithelium and enter mitotic arrest prior to upregulating Foxl2. Granulosa cells that populate the cortical primordial follicles activated in adult life derive from the surface epithelium perinatally, and enter mitotic arrest at that stage. Ingression from the surface epithelium dropped to undetectable levels by Postnatal Day 7, when most surviving oocytes were individually encapsulated by granulosa cells. These findings add complexity to the standard model of sex determination in which the Sertoli and granulosa cells of the adult testis and ovary directly stem from the supporting cell precursors of the bipotential gonad. PMID- 21976598 TI - Luteal microenvironment directs resident T lymphocyte function in cows. AB - The corpus luteum (CL) is a transient endocrine organ composed of a heterogeneous mixture of cells. Functional interactions exist between peripheral T cells and luteal cells in vitro; however, the precise role of resident T cells (RTC) remains unknown. The goals of the present study were to isolate RTC from within the CL and determine if alteration of luteal function resulted in changes in RTC phenotypes. Functional lymphocyte phenotypes identified in the bovine CL by using quantitative flow cytometric analysis were clearly different from those in the peripheral circulation. The proportion of CD8(+) RTC was greater than CD4(+) RTC. These proportions were opposite in peripheral blood. The proportion of gammadelta(+) lymphocytes was not different in the CL compared to that in peripheral blood nor was it altered during luteal regression. There was a significant increase in CD8alphaalpha(+) and gammadelta(+)CD8alphaalpha(+) RTC during luteal regression. The proportion of FOXP3(+) lymphocytes in the CL was greater than that isolated from peripheral blood, and this proportion of lymphocytes was dramatically reduced by induction of luteolysis. Within the CL of early pregnancy, there was an increase in the CD8alphabeta(+) and gammadelta(+)CD8alphabeta(+) populations compared to those in the CL of nonpregnant animals. Based on these data, we concluded that the functional state of the CL creates a microenvironment that regulates the recruitment of or differentiation into specific lymphocyte types. Understanding the interactions between steroidogenic cells and ovarian lymphocytes within CL will not only enhance understanding of reproductive function but may provide vital clues to lymphocyte regulation within tissues. PMID- 21976599 TI - Participation of the Cl-/HCO(3)- exchangers SLC26A3 and SLC26A6, the Cl- channel CFTR, and the regulatory factor SLC9A3R1 in mouse sperm capacitation. AB - Sperm capacitation is required for fertilization and involves several ion permeability changes. Although Cl(-) and HCO(3)(-) are essential for capacitation, the molecular entities responsible for their transport are not fully known. During mouse sperm capacitation, the intracellular concentration of Cl(-) ([Cl(-)](i)) increases and membrane potential (Em) hyperpolarizes. As in noncapacitated sperm, the Cl(-) equilibrium potential appears to be close to the cell resting Em, opening of Cl(-) channels could not support the [Cl(-)](i) increase observed during capacitation. Alternatively, the [Cl(-)](i) increase might be mediated by anion exchangers. Among them, SLC26A3 and SLC26A6 are good candidates, since, in several cell types, they increase [Cl(-)](i) and interact with cystic fibrosis transmembrane conductance regulator (CFTR), a Cl(-) channel present in mouse and human sperm. This interaction is known to be mediated and probably regulated by the Na(+)/H(+) regulatory factor-1 (official symbol, SLC9A3R1). Our RT-PCR, immunocytochemistry, Western blot, and immunoprecipitation data indicate that SLC26A3, SLC26A6, and SLC9A3R1 are expressed in mouse sperm, localize to the midpiece, and interact between each other and with CFTR. Moreover, we present evidence indicating that CFTR and SLC26A3 are involved in the [Cl(-)](i) increase induced by db-cAMP in noncapacitated sperm. Furthermore, we found that inhibitors of SLC26A3 (Tenidap and 5099) interfere with the Em changes that accompany capacitation. Together, these findings indicate that a CFTR/SLC26A3 functional interaction is important for mouse sperm capacitation. PMID- 21976600 TI - Rapid access cardiology--a nine year review. AB - BACKGROUND: Rapid access cardiology clinics provide a rapid assessment and evaluation of patients with suspected chest pain, heart failure or cardiac arrhythmia. Longitudinal data regarding the attendances and clinical diagnoses at rapid access clinics is lacking and may provide insight into their efficiency and role in providing a comprehensive referral service for primary care. METHODS: Data regarding total number of attendances and diagnoses were retrospectively analysed from databases collated by nurse specialists and physicians undertaking rapid access clinics at Charing Cross Hospital between April 2002 and March 2011. RESULTS: A total of 12 000 patients were seen over the 9-year time period. Demand for Rapid Access Chest Pain Clinic and Rapid Access Arrhythmia Clinic has shown a steady rise since 2007 whereas attendances at Rapid Access Heart Failure Clinic have remained constant. The proportion of patients diagnosed with significant cardiac disease across all rapid access clinics has not changed significantly. The most commonly diagnosed arrhythmia was atrial fibrillation (15% of all attendances). CONCLUSION: Referrals have increased to our service which suggests that demand for a rapid access cardiology service remains high and the proportion of patients diagnosed with significant cardiac disease has remained constant. Despite considerable motivation towards providing primary based care this has not occurred in our local area and we believe this shows that our model, based in secondary care to be both efficient and accessible to local GPs and patients. PMID- 21976601 TI - Liver abscess in a diabetic patient. PMID- 21976602 TI - Sporothrix schenckii and Sporotrichosis. AB - Sporotrichosis, which is caused by the dimorphic fungus Sporothrix schenckii, is currently distributed throughout the world, especially in tropical and subtropical zones. Infection generally occurs by traumatic inoculation of soil, plants, and organic matter contaminated with the fungus. Certain leisure and occupational activities, such as floriculture, agriculture, mining, and wood exploitation, are traditionally associated with the mycosis. Zoonotic transmission has been described in isolated cases or in small outbreaks. Since the end of the 1990s there has been an epidemic of sporotrichosis associated with transmission by cats in Rio de Janeiro, Brazil. More than 2,000 human cases and 3,000 animal cases have been reported. In humans, the lesions are usually restricted to the skin, subcutaneous cellular tissue, and adjacent lymphatic vessels. In cats, the disease can evolve with severe clinical manifestations and frequent systemic involvement. The gold standard for sporotrichosis diagnosis is culture. However, serological, histopathological, and molecular approaches have been recently adopted as auxiliary tools for the diagnosis of this mycotic infection. The first-choice treatment for both humans and cats is itraconazole. PMID- 21976604 TI - Current knowledge of Trichosporon spp. and Trichosporonosis. AB - Trichosporon spp. are basidiomycetous yeast-like fungi found widely in nature. Clinical isolates are generally related to superficial infections. However, this fungus has been recognized as an opportunistic agent of invasive infections, mostly in cancer patients and those exposed to invasive medical procedures. It is possible that the ability of Trichosporon strains to form biofilms on implanted devices, the presence of glucuronoxylomannan in their cell walls, and the ability to produce proteases and lipases are all factors likely related to the virulence of this genus and therefore may account for the progress of invasive trichosporonosis. Disseminated trichosporonosis has been increasingly reported worldwide and represents a challenge for both diagnosis and species identification. Phenotypic identification methods are useful for Trichosporon sp. screening, but only molecular methods, such as IGS region sequencing, allow the complete identification of Trichosporon isolates at the species level. Methods for the diagnosis of invasive trichosporonosis include PCR-based methods, Luminex xMAP technology, and, more recently, proteomics. Treating patients with trichosporonosis remains a challenge because of limited data on the in vitro and in vivo activities of antifungal drugs against clinically relevant species of the genus. Despite the mentioned limitations, the use of antifungal regimens containing triazoles appears to be the best therapeutic approach. PMID- 21976603 TI - Trypanosoma cruzi and Chagas' Disease in the United States. AB - Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and causes potentially life-threatening disease of the heart and gastrointestinal tract. The southern half of the United States contains enzootic cycles of T. cruzi, involving 11 recognized triatomine vector species. The greatest vector diversity and density occur in the western United States, where woodrats are the most common reservoir; other rodents, raccoons, skunks, and coyotes are also infected with T. cruzi. In the eastern United States, the prevalence of T. cruzi is highest in raccoons, opossums, armadillos, and skunks. A total of 7 autochthonous vector-borne human infections have been reported in Texas, California, Tennessee, and Louisiana; many others are thought to go unrecognized. Nevertheless, most T. cruzi-infected individuals in the United States are immigrants from areas of endemicity in Latin America. Seven transfusion-associated and 6 organ donor derived T. cruzi infections have been documented in the United States and Canada. As improved control of vector- and blood-borne T. cruzi transmission decreases the burden in countries where the disease is historically endemic and imported Chagas' disease is increasingly recognized outside Latin America, the United States can play an important role in addressing the altered epidemiology of Chagas' disease in the 21st century. PMID- 21976605 TI - Clinical manifestations, diagnosis, and treatment of Mycobacterium haemophilum infections. AB - Mycobacterium haemophilum is a slowly growing acid-fast bacillus (AFB) belonging to the group of nontuberculous mycobacteria (NTM) frequently found in environmental habitats, which can colonize and occasionally infect humans and animals. Several findings suggest that water reservoirs are a likely source of M. haemophilum infections. M. haemophilum causes mainly ulcerating skin infections and arthritis in persons who are severely immunocompromised. Disseminated and pulmonary infections occasionally occur. The second at-risk group is otherwise healthy children, who typically develop cervical and perihilar lymphadenitis. A full diagnostic regimen for the optimal detection of M. haemophilum includes acid fast staining, culturing at two temperatures with iron-supplemented media, and molecular detection. The most preferable molecular assay is a real-time PCR targeting an M. haemophilum-specific internal transcribed spacer (ITS), but another approach is the application of a generic PCR for a mycobacterium-specific fragment with subsequent sequencing to identify M. haemophilum. No standard treatment guidelines are available, but published literature agrees that immunocompromised patients should be treated with multiple antibiotics, tailored to the disease presentation and underlying degree of immune suppression. The outcome of M. haemophilum cervicofacial lymphadenitis in immunocompetent patients favors surgical intervention rather than antibiotic treatment. PMID- 21976606 TI - Food animals and antimicrobials: impacts on human health. AB - Antimicrobials are valuable therapeutics whose efficacy is seriously compromised by the emergence and spread of antimicrobial resistance. The provision of antibiotics to food animals encompasses a wide variety of nontherapeutic purposes that include growth promotion. The concern over resistance emergence and spread to people by nontherapeutic use of antimicrobials has led to conflicted practices and opinions. Considerable evidence supported the removal of nontherapeutic antimicrobials (NTAs) in Europe, based on the "precautionary principle." Still, concrete scientific evidence of the favorable versus unfavorable consequences of NTAs is not clear to all stakeholders. Substantial data show elevated antibiotic resistance in bacteria associated with animals fed NTAs and their food products. This resistance spreads to other animals and humans-directly by contact and indirectly via the food chain, water, air, and manured and sludge-fertilized soils. Modern genetic techniques are making advances in deciphering the ecological impact of NTAs, but modeling efforts are thwarted by deficits in key knowledge of microbial and antibiotic loads at each stage of the transmission chain. Still, the substantial and expanding volume of evidence reporting animal to-human spread of resistant bacteria, including that arising from use of NTAs, supports eliminating NTA use in order to reduce the growing environmental load of resistance genes. PMID- 21976610 TI - Fusion of a fluorescent protein to the pUL25 minor capsid protein of pseudorabies virus allows live-cell capsid imaging with negligible impact on infection. AB - In order to resolve the location and activity of submicroscopic viruses in living cells, viral proteins are often fused to fluorescent proteins (FPs) and visualized by microscopy. In this study, we describe the fusion of FPs to three proteins of pseudorabies virus (PRV) that allowed imaging of capsids in living cells. Included in this study are the first recombinant PRV strains expressing FP pUL25 fusions based on a design applied to herpes simplex virus type 1 by Homa and colleagues. The properties of each reporter virus were compared in both in vitro and in vivo infection models. PRV strains expressing FP-pUL25 and FP-pUL36 preserved wild-type properties better than traditional FP-pUL35 isolates in assays of plaque size and virulence in mice. The utility of these strains in studies of axon transport, nuclear dynamics and viral particle composition are documented. PMID- 21976607 TI - Human Metapneumovirus: lessons learned over the first decade. AB - It has been 10 years since human metapneumovirus (HMPV) was identified as a causative agent of respiratory illness in humans. Since then, numerous studies have contributed to a substantial body of knowledge on many aspects of HMPV. This review summarizes our current knowledge on HMPV, HMPV disease pathogenesis, and disease intervention strategies and identifies a number of areas with key questions to be addressed in the future. PMID- 21976611 TI - Natural and experimental infection of dogs with pandemic H1N1/2009 influenza virus. AB - Evidence of H1N1/2009 influenza virus infection was identified in two domestic dogs in China in November 2009. Virus isolation and sequence analysis of all eight genes of the two isolates showed that they were related closely to the H1N1/2009 influenza virus circulating in humans, indicating that they were probably acquired from humans. To determine the pathogenicity and transmissibility of H1N1/2009 influenza virus in dogs, experimental infection and transmission were performed. Inoculated dogs were able to shed virus in nasal secretions, but symptoms were very mild. Uninoculated dogs were co-mingled to determine the transmissibility of the isolate, and one of three exposed dogs was shown to develop infection. The present findings indicate that human H1N1/2009 can infect dogs, but is transmitted inefficiently between dogs. PMID- 21976609 TI - Immunodiagnosis of tuberculosis: a dynamic view of biomarker discovery. AB - Infection with Mycobacterium tuberculosis causes a variety of clinical conditions ranging from life-long asymptomatic infection to overt disease with increasingly severe tissue damage and a heavy bacillary burden. Immune biomarkers should follow the evolution of infection and disease because the host immune response is at the core of protection against disease and tissue damage in M. tuberculosis infection. Moreover, levels of immune markers are often affected by the antigen load. We review how the clinical spectrum of M. tuberculosis infection correlates with the evolution of granulomatous lesions and how granuloma structural changes are reflected in the peripheral circulation. We also discuss how antigen specific, peripheral immune responses change during infection and how these changes are associated with the physiology of the tubercle bacillus. We propose that a dynamic approach to immune biomarker research should overcome the challenges of identifying those asymptomatic and symptomatic stages of infection that require antituberculosis treatment. Implementation of such a view requires longitudinal studies and a systems immunology approach leading to multianalyte assays. PMID- 21976612 TI - Pharmaconutrition in acute lung injury. PMID- 21976608 TI - Serratia infections: from military experiments to current practice. AB - Serratia species, in particular Serratia marcescens, are significant human pathogens. S. marcescens has a long and interesting taxonomic, medical experimentation, military experimentation, and human clinical infection history. The organisms in this genus, particularly S. marcescens, were long thought to be nonpathogenic. Because S. marcescens was thought to be a nonpathogen and is usually red pigmented, the U.S. military conducted experiments that attempted to ascertain the spread of this organism released over large areas. In the process, members of both the public and the military were exposed to S. marcescens, and this was uncovered by the press in the 1970s, leading to U.S. congressional hearings. S. marcescens was found to be a certain human pathogen by the mid 1960s. S. marcescens and S. liquefaciens have been isolated as causative agents of numerous outbreaks and opportunistic infections, and the association of these organisms with point sources such as medical devices and various solutions given to hospitalized patients is striking. Serratia species appear to be common environmental organisms, and this helps to explain the large number of nosocomial infections due to these bacteria. Since many nosocomial infections are caused by multiply antibiotic-resistant strains of S. marcescens, this increases the danger to hospitalized patients, and hospital personnel should be vigilant in preventing nosocomial outbreaks due to this organism. S. marcescens, and probably other species in the genus, carries several antibiotic resistance determinants and is also capable of acquiring resistance genes. S. marcescens and S. liquefaciens are usually identified well in the clinical laboratory, but the other species are rare enough that laboratory technologists may not recognize them. 16S rRNA gene sequencing may enable better identification of some of the less common Serratia species. PMID- 21976614 TI - Extracorporeal membrane oxygenation as a first-line treatment strategy for ARDS: is the evidence sufficiently strong? PMID- 21976615 TI - Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A(H1N1). AB - CONTEXT: Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients with severe acute respiratory distress syndrome (ARDS), but its role has remained controversial. ECMO was used to treat patients with ARDS during the 2009 influenza A(H1N1) pandemic. OBJECTIVE: To compare the hospital mortality of patients with H1N1-related ARDS referred, accepted, and transferred for ECMO with matched patients who were not referred for ECMO. DESIGN, SETTING, AND PATIENTS: A cohort study in which ECMO-referred patients were defined as all patients with H1N1-related ARDS who were referred, accepted, and transferred to 1 of the 4 adult ECMO centers in the United Kingdom during the H1N1 pandemic in winter 2009 2010. The ECMO-referred patients and the non-ECMO-referred patients were matched using data from a concurrent, longitudinal cohort study (Swine Flu Triage study) of critically ill patients with suspected or confirmed H1N1. Detailed demographic, physiological, and comorbidity data were used in 3 different matching techniques (individual matching, propensity score matching, and GenMatch matching). MAIN OUTCOME MEASURE: Survival to hospital discharge analyzed according to the intention-to-treat principle. RESULTS: Of 80 ECMO-referred patients, 69 received ECMO (86.3%) and 22 died (27.5%) prior to discharge from the hospital. From a pool of 1756 patients, there were 59 matched pairs of ECMO referred patients and non-ECMO-referred patients identified using individual matching, 75 matched pairs identified using propensity score matching, and 75 matched pairs identified using GenMatch matching. The hospital mortality rate was 23.7% for ECMO-referred patients vs 52.5% for non-ECMO-referred patients (relative risk [RR], 0.45 [95% CI, 0.26-0.79]; P = .006) when individual matching was used; 24.0% vs 46.7%, respectively (RR, 0.51 [95% CI, 0.31-0.81]; P = .008) when propensity score matching was used; and 24.0% vs 50.7%, respectively (RR, 0.47 [95% CI, 0.31-0.72]; P = .001) when GenMatch matching was used. The results were robust to sensitivity analyses, including amending the inclusion criteria and restricting the location where the non-ECMO-referred patients were treated. CONCLUSION: For patients with H1N1-related ARDS, referral and transfer to an ECMO center was associated with lower hospital mortality compared with matched non ECMO-referred patients. PMID- 21976616 TI - Gh is produced by the testis of Japanese eel and stimulates proliferation of spermatogonia. AB - Gh plays important roles in development, somatic growth and gametogenesis in vertebrates. To determine the physiological role of Gh in reproduction in male teleosts, the expression of genes encoding Gh and the two Gh receptors (Ghrs) during spermatogenesis, and the action of Gh in vitro was examined using the Japanese eel (Anguilla japonica). gh, ghr1 and ghr2 mRNA transcripts were detected in all spermatogenic stages. In situ hybridization showed the presence of ghr1 and ghr2 mRNA in the germ cells. Immunohistochemistry using an antiserum against eel Gh indicated that Gh protein was localized to Sertoli cells surrounding the germ cells in early spermatogenesis. Recombinant eel Gh induced spermatogonial proliferation in a testis organ culture system, an effect that was independent from the production of steroid hormones or Igf1. This study identifies a role for eel Gh in the regulation of early spermatogenesis, particularly in the mitotic phase of spermatogenesis, that is not mediated by either steroid hormones or Igf1 production. PMID- 21976617 TI - X-linked inhibitor of apoptosis protein and active caspase-3 expression patterns in antral follicles in the sheep ovary. AB - X-linked inhibitor of apoptosis protein (XIAP) interacts with caspases to inhibit their activity, thereby providing a potential mechanism for regulation of granulosa cell apoptosis occurring during follicular atresia. The aim of this study was to determine the presence and localization of XIAP mRNA and protein content in the sheep ovary and compare these expression patterns with active caspase-3 protein in the same antral follicles. Romney ewe estrous cycles (n=25) were synchronized with 2-3 Estrumate injections and ovarian tissue collected during the luteal and follicular phases of the cycle. The presence of XIAP mRNA was confirmed by RT-PCR using laser capture microdissected ovarian cell samples. XIAP mRNA was subsequently localized by in situ hybridization histochemistry and XIAP and active caspase-3 protein visualized by immunohistochemistry. In antral follicles extensive XIAP localization was evident in both granulosa and thecal cells. In contrast, mRNA expression was widespread in granulosa cells and only detected in thecal tissue from a small proportion of antral follicles. Active caspase-3 and XIAP comparative expression analysis showed positive XIAP mRNA expression in all late luteal phase (day 14) follicles, despite varying levels of active caspase-3 protein. A proportion of follicular phase (days 15 and 16) follicles, however, showed an inverse expression relationship at the protein and mRNA levels in both granulosa and thecal tissue, as did XIAP protein in day 14 follicles. These results suggest high XIAP may prevent activation of caspase-3, thereby regulating follicular atresia in antral follicles and could potentially be utilized as a marker of follicular health. PMID- 21976618 TI - RNA-binding proteins, RNA granules, and gametes: is unity strength? AB - Changes in mRNA translation and degradation represent post-transcriptional processes operating during gametogenesis and early embryogenesis to ensure regulated protein synthesis. Numerous mRNA-binding proteins (RBPs) have been described in multiple animal models that contribute to the control of mRNA translation and decay during oogenesis and spermatogenesis. An emerging view from studies performed in germ cells and somatic cells is that RBPs associate with their target mRNAs in RNA-protein (or ribonucleoprotein) complexes (mRNPs) that assemble in various cytoplasmic RNA granules that communicate with the translation machinery and control mRNA storage, triage, and degradation. In comparison with Xenopus, Caenorhabditis elegans, or Drosophila, the composition and role of cytoplasmic RNA-containing granules in mammalian germ cells are still poorly understood. However, regained interest for these structures has emerged with the recent discovery of their role in small RNA synthesis and transposon silencing through DNA methylation. In this review, we will briefly summarize our current knowledge on cytoplasmic RNA granules in murine germ cells and describe the role of some of the RBPs they contain in regulating mRNA metabolism and small RNA processing during gametogenesis. PMID- 21976613 TI - Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in acute lung injury. AB - CONTEXT: The omega-3 (n-3) fatty acids docosahexaenoic acid and eicosapentaenoic acid, along with gamma-linolenic acid and antioxidants, may modulate systemic inflammatory response and improve oxygenation and outcomes in patients with acute lung injury. OBJECTIVE: To determine if dietary supplementation of these substances to patients with acute lung injury would increase ventilator-free days to study day 28. DESIGN, SETTING, AND PARTICIPANTS: The OMEGA study, a randomized, double-blind, placebo-controlled, multicenter trial conducted from January 2, 2008, through February 21, 2009. Participants were 272 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. All participants had complete follow-up. INTERVENTIONS: Twice-daily enteral supplementation of n-3 fatty acids, gamma-linolenic acid, and antioxidants compared with an isocaloric control. Enteral nutrition, directed by a protocol, was delivered separately from the study supplement. MAIN OUTCOME MEASURE: Ventilator-free days to study day 28. RESULTS: The study was stopped early for futility after 143 and 129 patients were enrolled in the n-3 and control groups. Despite an 8-fold increase in plasma eicosapentaenoic acid levels, patients receiving the n-3 supplement had fewer ventilator-free days (14.0 vs 17.2; P = .02) (difference, -3.2 [95% CI, -5.8 to 0.7]) and intensive care unit-free days (14.0 vs 16.7; P = .04). Patients in the n-3 group also had fewer nonpulmonary organ failure-free days (12.3 vs 15.5; P = .02). Sixty-day hospital mortality was 26.6% in the n-3 group vs 16.3% in the control group (P = .054), and adjusted 60-day mortality was 25.1% and 17.6% in the n-3 and control groups, respectively (P = .11). Use of the n-3 supplement resulted in more days with diarrhea (29% vs 21%; P = .001). CONCLUSIONS: Twice daily enteral supplementation of n-3 fatty acids, gamma-linolenic acid, and antioxidants did not improve the primary end point of ventilator-free days or other clinical outcomes in patients with acute lung injury and may be harmful. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00609180. PMID- 21976619 TI - gamma-Hydroxybutyrate blood/plasma partitioning: effect of physiologic pH on transport by monocarboxylate transporters. AB - The drug of abuse gamma-hydroxybutyrate (GHB) displays nonlinear renal clearance, which has been attributed to saturable renal reabsorption by monocarboxylate transporters (MCTs) present in the kidney. MCT1 is also present in red blood cells (RBCs); however, the significance of this transporter on the blood/plasma partitioning of GHB is unknown. The purpose of this research was to characterize the transport of GHB across the RBC membrane and assess GHB blood/plasma partitioning in vivo in the presence and absence of a competitive MCT inhibitor, l-lactate. In vitro experiments were performed using freshly isolated rat erythrocytes at pH values of 6.5 and 7.4. Inhibition with p-chloromercuribenzene sulfonate and 4,4'-diisothiocyanostilbene-2,2'-disulfonate were used to determine the contribution of MCT1 and band 3, respectively, on GHB uptake. For in vivo experiments, rats were administered GHB (400-1500 mg/kg) with and without l lactate. In vitro experiments demonstrated that GHB is transported across the RBC membrane primarily by MCT1 at relevant in vivo concentrations. The K(m) for MCT1 was lower at pH 6.5 than that at pH 7.4, 2.2 versus 17.0 mM, respectively. The in vivo blood/plasma partitioning of GHB displayed linearity across all concentrations. l-Lactate coadministration increased GHB renal clearance but had no effect on the blood/plasma ratio. Unlike its MCT-mediated transport in the intestine and kidneys, GHB blood/plasma partitioning appears to be linear and is unaffected by l-lactate. These findings can be attributed, at least in part, to differences in physiologic pH at different sites of MCT-mediated transport. PMID- 21976620 TI - Debrisoquine metabolism and CYP2D expression in marmoset liver microsomes. AB - The objective of this study was to define CYP2D enzymes in marmoset (Callithrix jacchus) liver microsomes, both at the activity level using debrisoquine as the model substrate and at the protein level using antibodies raised to human CYP2D6. Marmoset liver microsomes were incubated with [(14)C]debrisoquine, and the structure of the generated metabolites was determined using liquid chromatography tandem mass spectrometry and NMR. Marmoset liver microsomes were very effective in hydroxylating debrisoquine at various positions. Although 4 hydroxydebrisoquine was formed, in contrast to rat and human it was only a minor metabolite. Debrisoquine was more extensively hydroxylated in the 7, 5, 6, and 8 positions. In addition to the monohydroxylated metabolites, a dihydroxy metabolite, namely 6,7-dihydroxydebrisoquine, was identified. Finally, metabolites that had undergone ring opening were also detected but were not investigated further. Antibodies to CYP2D6 immunoreacted with protein in marmoset and human but not rat hepatic microsomes. In conclusion, we demonstrate that marmoset liver microsomes are effective in hydroxylating debrisoquine at various positions and that they contain a protein that is immunorelated to human CYP2D6. PMID- 21976621 TI - Prediction of CYP2D6 drug interactions from in vitro data: evidence for substrate dependent inhibition. AB - Predicting the magnitude of potential drug-drug interactions is important for underwriting patient safety in the clinical setting. Substrate-dependent inhibition of cytochrome P450 enzymes may confound extrapolation of in vitro results to the in vivo situation. However, the potential for substrate-dependent inhibition with CYP2D6 has not been well characterized. The inhibition profiles of 20 known inhibitors of CYP2D6 were characterized in vitro against four clinically relevant CYP2D6 substrates (desipramine, dextromethorphan, metoprolol, and thioridazine) and bufuralol. Dextromethorphan exhibited the highest sensitivity to in vitro inhibition, whereas metoprolol was the least sensitive. In addition, when metoprolol was the substrate, inhibitors with structurally constrained amino moieties (clozapine, debrisoquine, harmine, quinidine, and yohimbine) exhibited at least a 5-fold decrease in inhibition potency when results were compared with those for dextromethorphan. Atypical inhibition kinetics were observed for these and other inhibitor-substrate pairings. In silico docking studies suggested that interactions with Glu216 and an adjacent hydrophobic binding pocket may influence substrate sensitivity and inhibition potency for CYP2D6. The in vivo sensitivities of the clinically relevant CYP2D6 substrates desipramine, dextromethorphan, and metoprolol were determined on the basis of literature drug-drug interaction (DDI) outcomes. Similar to the in vitro results, dextromethorphan exhibited the highest sensitivity to CYP2D6 inhibition in vivo. Finally, the magnitude of in vivo CYP2D6 DDIs caused by quinidine was predicted using desipramine, dextromethorphan, and metoprolol. Comparisons of the predictions with literature results indicated that the marked decrease in inhibition potency observed for the metoprolol-quinidine interaction in vitro translated to the in vivo situation. PMID- 21976622 TI - Potential contribution of cytochrome P450 2B6 to hepatic 4 hydroxycyclophosphamide formation in vitro and in vivo. AB - Results from retrospective studies on the relationship between cytochrome P450 (P450) 2B6 (CYP2B6) genotype and cyclophosphamide (CY) efficacy and toxicity in adult cancer patients have been conflicting. We evaluated this relationship in children, who have faster CY clearance and receive different CY-based regimens than adults. These factors may influence the P450s metabolizing CY to 4 hydroxycyclophosphamide (4HCY), the principal precursor to CY's cytotoxic metabolite. Therefore, we sought to characterize the in vitro and in vivo roles of hepatic CYP2B6 and its main allelic variants in 4HCY formation. CYP2B6 is the major isozyme responsible for 4HCY formation in recombinant P450 Supersomes. In human liver microsomes (HLM), 4HCY formation correlated with known phenotypic markers of CYP2B6 activity, specifically formation of (S)-2-ethyl-1,5-dimethyl 3,3-diphenyl pyrrolidine and hydroxybupropion. However, in HLM, CYP3A4/5 also contributes to 4HCY formation at the CY concentrations similar to plasma concentrations achieved in children (0.1 mM). 4HCY formation was not associated with CYP2B6 genotype at low (0.1 mM) or high (1 mM) CY concentrations potentially because CYP3A4/5 and other isozymes also form 4HCY. To remove this confounder, 4HCY formation was evaluated in recombinant CYP2B6 enzymes, which demonstrated that 4HCY formation was lower for CYP2B6.4 and CYP2B6.5 compared with CYP2B6.1. In vivo, CYP2B6 genotype was not directly related to CY clearance or ratio of 4HCY/CY areas under the curve in 51 children receiving CY-based regimens. Concomitant chemotherapy agents did not influence 4HCY formation in vitro. We conclude that CYP2B6 genotype is not consistently related to 4HCY formation in vitro or in vivo. PMID- 21976623 TI - Increased IGF1 levels in relation to heart failure and cardiovascular mortality in an elderly population: impact of ACE inhibitors. AB - OBJECTIVE: There are conflicting results regarding the association of circulating IGF1 with cardiovascular (CV) morbidity and mortality. We assessed the relationship between IGF1 levels and heart failure (HF), ischemic heart disease (IHD), and CV mortality in an elderly population taking into account the possible impact of angiotensin converting enzyme (ACE) inhibitors. DESIGN AND METHODS: A total of 851 persons aged 66-81 years, in a rural Swedish municipality, were subjected to medical history, clinical examination, electrocardiography, echocardiography, and fasting plasma samples. They were then followed for 8 years. RESULTS AND CONCLUSION: Patients on ACE inhibitors had higher IGF1 levels compared with those without ACE inhibitors. In patients on ACE inhibitors, higher IGF1 values were found in patients with an ejection fraction (EF) <40% compared with EF >=40%, in patients with higher proBNP levels in quartile 4 vs 1, and in patients with IHD when compared to those without ACE inhibitors (P<0.001). In patients without ACE inhibitors, no relationship was found between IGF1 levels and HF or IHD. In multivariate regression, only ACE inhibitors, ECG changes characteristic for IHD, and gender had a significant impact on IGF1. Patients with higher IGF1 levels in quintiles 4 and 5 compared to quintiles 1 and 2 had a 50% higher risk for CV death (P=0.03). This was significant after adjustment for well-known CV risk factors and ACE inhibitors (P=0.03). CONCLUSIONS: Our results show that treatment with ACE inhibitors in an elderly population is associated with increased IGF1 levels, especially in patients with impaired cardiac function or IHD. High IGF1 levels tend to be associated with an increased risk for CV mortality. PMID- 21976624 TI - Male sexual harassment alters female social behaviour towards other females. AB - Male harassment of females to gain mating opportunities is a consequence of an evolutionary conflict of interest between the sexes over reproduction and is common among sexually reproducing species. Male Trinidadian guppies Poecilia reticulata spend a large proportion of their time harassing females for copulations and their presence in female social groups has been shown to disrupt female-female social networks and the propensity for females to develop social recognition based on familiarity. In this study, we investigate the behavioural mechanisms that may lead to this disruption of female sociality. Using two experiments, we test the hypothesis that male presence will directly affect social behaviours expressed by females towards other females in the population. In experiment one, we tested for an effect of male presence on female shoaling behaviour and found that, in the presence of a free-swimming male guppy, females spent shorter amounts of time with other females than when in the presence of a free-swimming female guppy. In experiment two, we tested for an effect of male presence on the incidence of aggressive behaviour among female guppies. When males were present in a shoal, females exhibited increased levels of overall aggression towards other females compared with female only shoals. Our work provides direct evidence that the presence of sexually harassing males alters female-female social behaviour, an effect that we expect will be recurrent across taxonomic groups. PMID- 21976625 TI - Scared and less noisy: glucocorticoids are associated with alarm call entropy. AB - The nonlinearity and arousal hypothesis predicts that highly aroused mammals will produce nonlinear, noisy vocalizations. We tested this prediction by measuring faecal glucocorticoid metabolites (GCMs) in adult yellow-bellied marmots (Marmota flaviventris), and asking if variation in GCMs was positively correlated with Wiener entropy-a measure of noise. Contrary to our prediction, we found a significant negative relationship: marmots with more faecal GCMs produced calls with less noise than those with lower levels of GCMs. A previous study suggested that glucocorticoids modulate the probability that a marmot will emit a call. This study suggests that, like some other species, calls emitted from highly aroused individuals are less noisy. Glucocorticoids thus play an important, yet underappreciated role, in alarm call production. PMID- 21976626 TI - Radiation protection in fixed PET/CT facilities--design and operation. AB - We describe the design of a fixed positron emission tomography (PET)/CT facility and the use of a simulated instantaneous dose-rate plot to visually highlight areas of potentially high radiation exposure. We also illustrate the practical implementation of basic radiation protection principles based on the use of distance and shielding and the minimisation of time spent in hot areas. Staff whole body doses for 4 years are presented with results of an optimisation study analysing the dose arising from the different phases within each study using direct reading dosemeters. The total whole body dose for all staff for each patient fell from 9.5 MUSv in the first full year of operation to 4.8 uSv in 2008. The maximum dose to an individual member of staff per patient decreased over the same period from 3.2 to 0.9 uSv. The optimisation study showed that the highest dose was recorded during the injection phase. PMID- 21976627 TI - Electronic portal imaging vs kilovoltage imaging in fiducial marker image-guided radiotherapy for prostate cancer: an analysis of set-up uncertainties. AB - OBJECTIVES: The purpose of this study was to compare interfraction prostate displacement data between electronic portal imaging (EPI) and kilovoltage imaging (KVI) treatment units and discuss the impact of any difference on margin calculations for prostate cancer image-guided radiotherapy (IGRT). METHODS: Prostate interfraction displacement data was collected prospectively for the first 4 fractions in 333 patients treated with IGRT with daily pre-treatment EPI or KVI orthogonal imaging. Displacement was recorded in the anteroposterior (AP), left-right (LR) and superoinferior (SI) directions. The proportion of displacement <3 mm and the difference in median absolute displacements were calculated in all directions. RESULTS: 1088 image pairs were analysed in total, 448 by EPI and 640 by KVI. There were 23% (95% confidence interval [CI] 18-28%) more displacements under 3 mm for EPI than for KVI in the AP direction, 14% (95% CI 10-19%) more in the LR direction and 10% (95% CI 5-15%) more in the SI direction. The differences in absolute median displacement (KVI>EPI) were AP 1 mm, LR 1 mm and SI 0.5 mm. Wilcoxon rank-sum test showed that distributions were significantly different for all three dimensions (p<0.0001 for AP and LR and p=0.02 for SI). CONCLUSION: EPI has a statistically significant smaller set-up error distribution than KVI. We would expect that, because fiducial marker imaging is less clear for EPI, the clinical target volume to planning target volume margin would be greater when using IGRT; however, relying wholly on displacement data gives the opposite result. We postulate that this is owing to observer bias, which is not accounted for in margin calculation formulas. PMID- 21976628 TI - Enlargement of the spleen as an incidental finding on CT in post-partum females with fever. AB - OBJECTIVE: The aim was to evaluate whether enlargement of the spleen on CT in a post-partum female with fever is a common phenomenon. METHODS: In this retrospective institutional review board-approved study, the spleen was measured by CT in 77 females (average age 30.7 years) examined for post-partum fever and a control group of 58 febrile females imaged for suspected appendicitis (average age 29.7 years). The splenic length, width and thickness were measured and used to calculate the splenic index. The measurements of both groups of patients were compared. The size of the spleen was assessed again in 12 of the 77 post-partum female who had a follow-up CT for unrelated reasons. Continuous variables were compared, by groups, using analysis of variance (ANOVA). ANOVA with repeated measures was used to evaluate changes over time. A p-value <0.05 was considered significant. RESULTS: The length, thickness and width of the spleen were significantly larger in the patients imaged after delivery compared with those in the control group (p<0.001 for all three comparisons). The mean splenic index was 686.6 cm(3) in the post-partum group and 408.1 cm(3) in the control group (p<0.001). The splenic dimensions and index were significantly smaller in the 12 post-partum females who had a follow-up study. CONCLUSION: An enlarged spleen in febrile females undergoing CT in the puerperium may reflect physiological changes occurring during pregnancy. PMID- 21976629 TI - Chest radiographic findings of pulmonary tuberculosis in severely immunocompromised patients with the human immunodeficiency virus. AB - OBJECTIVE: We describe chest radiograph (CXR) findings in a population with a high prevalence of human immunodeficiency virus (HIV) and tuberculosis (TB) in order to identify radiological features associated with TB; to compare CXR features between HIV-seronegative and HIV-seropositive patients with TB; and to correlate CXR findings with CD4 T-cell count. METHODS: Consecutive adult patients admitted to a national referral hospital with a cough of duration of 2 weeks or longer underwent diagnostic evaluation for TB and other pneumonias, including sputum examination and mycobacterial culture, bronchoscopy and CXR. Two radiologists blindly reviewed CXRs using a standardised interpretation form. RESULTS: Smear or culture-positive TB was diagnosed in 214 of 403 (53%) patients. Median CD4+ T-cell count was 50 cells mm(-3) [interquartile range (IQR) 14-150]. TB patients were less likely than non-TB patients to have a normal CXR (12% vs 20%, p = 0.04), and more likely than non-TB patients to have a diffuse pattern of opacities (75% vs 60%, p = 0.003), reticulonodular opacities (45% vs 12%, p < 0.001), nodules (14% vs 6%, p = 0.008) or cavities (18% vs 7%, p = 0.001). HIV seronegative TB patients more often had consolidation (70% vs 42%, p = 0.007) and cavities (48% vs 13%, p < 0.001) than HIV-seropositive TB patients. TB patients with a CD4+ T-cell count of <= 50 cells mm(-3) less often had consolidation (33% vs 54%, p = 0.006) and more often had hilar lymphadenopathy (30% vs 16%, p = 0.03) compared with patients with CD4 51-200 cells mm(-3). CONCLUSION: Although different CXR patterns can be seen in TB and non-TB pneumonias there is considerable overlap in features, especially among HIV-seropositive and severely immunosuppressed patients. Providing clinical and immunological information to the radiologist might improve the accuracy of radiographic diagnosis of TB. PMID- 21976630 TI - Familial ossification of the stylohyoid ligament in a three generation family--a new clinical entity displaying autosomal dominant inheritance. AB - Ossification of the stylohyoid ligament is very common in the Caucasian population. More than 9000 descriptions of apparently isolated case reports on PubMed have been cited over the last 20 years, often associated with an incidental finding on imaging after neck trauma. No cases of familial ossification have been described. We document a family with several affected members, each with an ossified stylohyoid ligament, confirming that ossification may be hereditary in some families and is most likely due to an autosomal dominant gene. PMID- 21976631 TI - Dose exposure in the ITALUNG trial of lung cancer screening with low-dose CT. AB - Few data are available on the effective dose received by participants in lung cancer screening programmes with low-dose CT (LDCT). We report the collective effective dose delivered to 1406 current or former smokers enrolled in the ITALUNG trial who completed 4 annual LDCT examinations and related further investigations including follow-up LDCT, 2-[(18)F]flu-2-deoxy-d-glucose positron emission tomography (FDG-PET) or CT-guided fine needle aspiration biopsy (FNAB). Using the air CT dose index and Monte Carlo simulations on an anthropomorphic phantom, the whole-body effective dose associated with LDCT was determined for the eight CT scanners used in the trial. A value of 7 mSv was assigned to FDG-PET while the measured mean effective dose of CT-guided FNAB was 1.5 mSv. The mean collective effective dose in the 1406 subjects ranged between 8.75 and 9.36 Sv and the mean effective dose to the single subject over 4 years was between 6.2 and 6.8 mSv (range 1.7-21.5 mSv) according to the cranial-caudal length of the LDCT volume. 77.4% of the dose was owing to annual LDCT and 22.6% to further investigations. Considering the nominal risk coefficients for stochastic effects after exposure to low-dose radiation according to the National Radiological Protection Board, International Commission on Radiological Protection (ICRP) 60, ICRP103 and Biological Effects of Ionizing Radiation VII, the mean number of radiation-induced cancers ranged between 0.12 and 0.33 per 1000 subjects. The individual effective dose to participants in a 4-year lung cancer screening programme with annual LDCT is very low and about one-third of the effective dose that is associated with natural background radiation and diagnostic radiology in the same time period. PMID- 21976632 TI - Commentary. CT stroke window settings: an unfortunate misleading misnomer? AB - This commentary will discuss the use of the "stroke window" settings in the evaluation of CT head examinations and advocate their more widespread use in patients who present with neurological symptoms in addition to patients with suspected stroke. We present examples of the use of stroke windows, which revealed subtle abnormalities that were not readily apparent on default brain window settings and were subsequently confirmed on MRI or follow-up CT. As a result we suggest that stroke windows should be routine in the review of all CT head examinations. PMID- 21976633 TI - Assessment of correlation between CT angiographic clot load score, pulmonary perfusion defect score and global right ventricular function with dual-source CT for acute pulmonary embolism. AB - OBJECTIVE: The purpose of this study was to prospectively investigate the correlation between CT angiographic clot load (CTACL) score, pulmonary perfusion defect (PPD) score and the global right ventricular function in the assessment of pulmonary embolism (PE) severity. METHODS: 49 patients with acute PE, who underwent dual-source CT scan, were included in the study. CT angiography and perfusion imaging were performed. Data from electrocardiogram-gated coronary angiography scanning protocol were used for right ventricular function analysis. Two readers evaluated the CTACL and PPD scores using the Qanadli and Chae methods, respectively. RESULTS: The PPD score had a strong positive correlation with the CTACL score (r=0.72, p<0.001) and both scores in turn had a strong positive correlation with the right ventricular/left ventricular (RV/LV) diameter ratio (r=0.60, r=0.62, p<0.001). However, the PPD score had a strong negative correlation with ejection fraction (EF) (r=-0.63, p<0.001) while the CTACL score had a low negative correlation with EF (r=-0.33, p=0.02). Between the RV/LV<1 group (n=35) and the RV/LV >1 group (n=14), the PPD score, CTACL score, pulmonary artery trunk diameter, EF and reflux of inferior vena cava were significantly different, all with p<0.001. The end-systolic volume (p=0.01) was significantly different but the end-diastolic volume (p=0.11) and stroke volume (p=0.08) showed no statistically significant difference between the two groups. CONCLUSION: Therefore, considering PPD scores, CTACL scores and cardiovascular manifestations together may be helpful in the evaluation of PE severity. PMID- 21976634 TI - Yttrium-90 internal pair production imaging using first generation PET/CT provides high-resolution images for qualitative diagnostic purposes. AB - Yttrium-90 ((90)Y) internal pair production can be imaged by positron emission tomography (PET)/CT and is superior to bremsstrahlung single-photon emission CT/CT for evaluating hepatic (90)Y microsphere biodistribution. We illustrate a case of (90)Y imaging using first generation PET/CT technology, producing high quality images for qualitative diagnostic purposes. PMID- 21976635 TI - Calibration of the modified Huddart and Bodenham scoring system against the GOSLON/5-year-olds' index for unilateral cleft lip and palate. AB - The GOSLON/5-year-old scoring systems have been used in various national and international studies. This study aims to identify the range of Modified Huddart and Bodenham (MHB) scores, which correlate with each GOSLON and 5-year-old category and thereby create a new scoring system that allows comparison with historical data. Two hundred and eighty-three unilateral cleft lip and palate study models from England and Scotland that had all been previously scored using the 5-year-old and GOSLON indices by calibrated examiners were scored using MHB on two separate occasions a month apart by two examiners. Reliability analysis using intraclass correlation and Bland Altman plots were performed. Ordinal regression was used to define the categories of MHB that correspond to the 5-year old and GOSLON categories. The results revealed a high level of repeatability for both the 5 and the 10 year old models. The MHB scale was grouped into the five categories of the GOSLON and 5-year-old indices with more precision for the 5 year than the 10 year scores. In conclusion, there was high intra-examiner and inter-examiner agreement using the MHB scoring system. It also correlates well with the 5-year-old and GOSLON indices and has been shown to be a much more sensitive scoring system. PMID- 21976636 TI - Marijuana use and motor vehicle crashes. AB - Since 1996, 16 states and the District of Columbia in the United States have enacted legislation to decriminalize marijuana for medical use. Although marijuana is the most commonly detected nonalcohol drug in drivers, its role in crash causation remains unsettled. To assess the association between marijuana use and crash risk, the authors performed a meta-analysis of 9 epidemiologic studies published in English in the past 2 decades identified through a systematic search of bibliographic databases. Estimated odds ratios relating marijuana use to crash risk reported in these studies ranged from 0.85 to 7.16. Pooled analysis based on the random-effects model yielded a summary odds ratio of 2.66 (95% confidence interval: 2.07, 3.41). Analysis of individual studies indicated that the heightened risk of crash involvement associated with marijuana use persisted after adjustment for confounding variables and that the risk of crash involvement increased in a dose-response fashion with the concentration of 11-nor-9-carboxy-delta-9-tetrahydrocannabinol detected in the urine and the frequency of self-reported marijuana use. The results of this meta-analysis suggest that marijuana use by drivers is associated with a significantly increased risk of being involved in motor vehicle crashes. PMID- 21976637 TI - A formal mathematical framework for physiological observations, experiments and analyses. AB - Experiments can be complex and produce large volumes of heterogeneous data, which make their execution, analysis, independent replication and meta-analysis difficult. We propose a mathematical model for experimentation and analysis in physiology that addresses these problems. We show that experiments can be composed from time-dependent quantities, and be expressed as purely mathematical equations. Our structure for representing physiological observations can carry information of any type and therefore provides a precise ontology for a wide range of observations. Our framework is concise, allowing entire experiments to be defined unambiguously in a few equations. In order to demonstrate that our approach can be implemented, we show the equations that we have used to run and analyse two non-trivial experiments describing visually stimulated neuronal responses and dynamic clamp of vertebrate neurons. Our ideas could provide a theoretical basis for developing new standards of data acquisition, analysis and communication in neurophysiology. PMID- 21976638 TI - Edge-based compartmental modelling for infectious disease spread. AB - The primary tool for predicting infectious disease spread and intervention effectiveness is the mass action susceptible-infected-recovered model of Kermack & McKendrick. Its usefulness derives largely from its conceptual and mathematical simplicity; however, it incorrectly assumes that all individuals have the same contact rate and partnerships are fleeting. In this study, we introduce edge based compartmental modelling, a technique eliminating these assumptions. We derive simple ordinary differential equation models capturing social heterogeneity (heterogeneous contact rates) while explicitly considering the impact of partnership duration. We introduce a graphical interpretation allowing for easy derivation and communication of the model and focus on applying the technique under different assumptions about how contact rates are distributed and how long partnerships last. PMID- 21976639 TI - Genomic analysis of the vaccinia virus strain variants found in Dryvax vaccine. AB - Smallpox was eradicated using variant forms of vaccinia virus-based vaccines. One of these was Dryvax, a calf lymph vaccine derived from the New York City Board of Health strain. We used genome-sequencing technology to examine the genetic diversity of the population of viruses present in a sample of Dryvax. These studies show that the conserved cores of these viruses exhibit a lower level of sequence variation than do the telomeres. However, even though the ends of orthopoxviruses are more genetically plastic than the cores, there are still many telomeric genes that are conserved as intact open reading frames in the 11 genomes that we, and 4 genomes that others, have sequenced. Most of these genes likely modulate inflammation. Our sequencing also detected an evolving pattern of mutation, with some genes being highly fragmented by randomly assorting mutations (e.g., M1L), while other genes are intact in most viruses but have been disrupted in individual strains (e.g., I4L in strain DPP17). Over 85% of insertion and deletion mutations are associated with repeats, and a rare new isolate bearing a large deletion in the right telomere was identified. All of these strains cluster in dendrograms consistent with their origin but which also surprisingly incorporate horsepox virus. However, these viruses also exhibit a "patchy" pattern of polymorphic sites characteristic of recombinants. There is more genetic diversity detected within a vial of Dryvax than between variola virus major and minor strains, and our study highlights how propagation methods affect the genetics of orthopoxvirus populations. PMID- 21976640 TI - Virus-host coevolution in a persistently coxsackievirus B3-infected cardiomyocyte cell line. AB - Coevolution of virus and host is a process that emerges in persistent virus infections. Here we studied the coevolutionary development of coxsackievirus B3 (CVB3) and cardiac myocytes representing the major target cells of CVB3 in the heart in a newly established persistently CVB3-infected murine cardiac myocyte cell line, HL-1(CVB3). CVB3 persistence in HL-1(CVB3) cells represented a typical carrier-state infection with high levels (10(6) to 10(8) PFU/ml) of infectious virus produced from only a small proportion (approximately 10%) of infected cells. CVB3 persistence was characterized by the evolution of a CVB3 variant (CVB3-HL1) that displayed strongly increased cytotoxicity in the naive HL-1 cell line and showed increased replication rates in cultured primary cardiac myocytes of mouse, rat, and naive HL-1 cells in vitro, whereas it was unable to establish murine cardiac infection in vivo. Resistance of HL-1(CVB3) cells to CVB3-HL1 was associated with reduction of coxsackievirus and adenovirus receptor (CAR) expression. Decreasing host cell CAR expression was partially overcome by the CVB3-HL1 variant through CAR-independent entry into resistant cells. Moreover, CVB3-HL1 conserved the ability to infect cells via CAR. The employment of a soluble CAR variant resulted in the complete cure of HL-1(CVB3) cells with respect to the adapted virus. In conclusion, this is the first report of a CVB3 carrier-state infection in a cardiomyocyte cell line, revealing natural coevolution of CAR downregulation with CAR-independent viral entry in resistant host cells as an important mechanism of induction of CVB3 persistence. PMID- 21976641 TI - Substitutions in the glycoprotein (GP) of the Candid#1 vaccine strain of Junin virus increase dependence on human transferrin receptor 1 for entry and destabilize the metastable conformation of GP. AB - Candid#1 (Cd1) is an attenuated vaccine strain of Junin virus, the causative agent of Argentine hemorrhagic fever. Although several substitutions are present in Cd1, their importance for attenuation has not been established. We functionally characterized the substitutions present in the Cd1 glycoprotein (GP) and identified F427I in the transmembrane domain of the GP2 subunit as reducing infectivity in a reconstituted viral system. We further showed that this phenotype derives from the destabilization of the GP metastable conformation. Lastly, we identified an increased dependence of Cd1 GP on human transferrin receptor type 1 (hTfR-1) for entry, which may affect the tropism of the attenuated strain in vivo. PMID- 21976642 TI - The C-terminal region of lymphocytic choriomeningitis virus nucleoprotein contains distinct and segregable functional domains involved in NP-Z interaction and counteraction of the type I interferon response. AB - Several arenaviruses cause hemorrhagic fever (HF) disease in humans that is associated with high morbidity and significant mortality. Arenavirus nucleoprotein (NP), the most abundant viral protein in infected cells and virions, encapsidates the viral genome RNA, and this NP-RNA complex, together with the viral L polymerase, forms the viral ribonucleoprotein (vRNP) that directs viral RNA replication and gene transcription. Formation of infectious arenavirus progeny requires packaging of vRNPs into budding particles, a process in which arenavirus matrix-like protein (Z) plays a central role. In the present study, we have characterized the NP-Z interaction for the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV). The LCMV NP domain that interacted with Z overlapped with a previously documented C-terminal domain that counteracts the host type I interferon (IFN) response. However, we found that single amino acid mutations that affect the anti-IFN function of LCMV NP did not disrupt the NP-Z interaction, suggesting that within the C-terminal region of NP different amino acid residues critically contribute to these two distinct and segregable NP functions. A similar NP-Z interaction was confirmed for the HF arenavirus Lassa virus (LASV). Notably, LCMV NP interacted similarly with both LCMV Z and LASV Z, while LASV NP interacted only with LASV Z. Our results also suggest the presence of a conserved protein domain within NP but with specific amino acid residues playing key roles in determining the specificity of NP-Z interaction that may influence the viability of reassortant arenaviruses. In addition, this NP-Z interaction represents a potential target for the development of antiviral drugs to combat human-pathogenic arenaviruses. PMID- 21976643 TI - The cargo-binding domain of transportin 3 is required for lentivirus nuclear import. AB - Lentiviruses, unlike the gammaretroviruses, are able to infect nondividing cells by transiting through nuclear pores to access the host genomic DNA. Several nuclear import and nuclear pore components have been implicated as playing a role in nuclear import, including transportin 3 (TNPO3), a member of the importin-beta family of nuclear import proteins. We demonstrated that TNPO3 was required by several lentiviruses, with simian immunodeficiency virus mac239 (SIVmac239) and equine infectious anemia virus (EIAV) the most dependent and human immunodeficiency virus type 1 (HIV-1) and feline immunodeficiency virus (FIV) the least. Analysis of HIV-1/SIVmac239 chimeric viruses showed that dependence on TNPO3 mapped to the SIVmac239 capsid. Mutation of a single amino acid, A76V in the SIVmac239 capsid, rendered the virus TNPO3 independent and resistant to mCPSF6-358, a truncated splicing factor that prevents HIV-1 nuclear import. Using a complementation assay based on 293T cells that express a TNPO3-targeted short hairpin RNA (shRNA), we showed that the Drosophila TNPO3 homologue can substitute for its human counterpart and that it mapped a key functional domain of TNPO3 to the carboxy-terminal cargo-binding domain. Within the cargo-binding domain, two hydrophobic motifs were required for TNPO3-dependent infection. The mutated TNPO3 proteins maintained their ability to localize to the nucleus, suggesting that their inability to restore lentivirus infection resulted from an inability to bind to a host or viral cargo protein. PMID- 21976644 TI - White spot syndrome virus induces metabolic changes resembling the warburg effect in shrimp hemocytes in the early stage of infection. AB - The Warburg effect is an abnormal glycolysis response that is associated with cancer cells. Here we present evidence that metabolic changes resembling the Warburg effect are induced by a nonmammalian virus. When shrimp were infected with white spot syndrome virus (WSSV), changes were induced in several metabolic pathways related to the mitochondria. At the viral genome replication stage (12 h postinfection [hpi]), glucose consumption and plasma lactate concentration were both increased in WSSV-infected shrimp, and the key enzyme of the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PDH), showed increased activity. We also found that at 12 hpi there was no alteration in the ADP/ATP ratio and that oxidative stress was lower than that in uninfected controls. All of these results are characteristic of the Warburg effect as it is present in mammals. There was also a significant decrease in triglyceride concentration starting at 12 hpi. At the late stage of the infection cycle (24 hpi), hemocytes of WSSV-infected shrimp showed several changes associated with cell death. These included the induction of mitochondrial membrane permeabilization (MMP), increased oxidative stress, decreased glucose consumption, and disrupted energy production. A previous study showed that WSSV infection led to upregulation of the voltage-dependent anion channel (VDAC), which is known to be involved in both the Warburg effect and MMP. Here we show that double-stranded RNA (dsRNA) silencing of the VDAC reduces WSSV-induced mortality and virion copy number. For these results, we hypothesize a model depicting the metabolic changes in host cells at the early and late stages of WSSV infection. PMID- 21976645 TI - Vaginal langerhans cells nonproductively transporting HIV-1 mediate infection of T cells. AB - Although implied by other models, proof that Langerhans cells (LCs) in the human vagina participate in dissemination of infectious human immunodeficiency virus type 1 (HIV-1) has been lacking. Here, we show that LCs migrate from HIV-1 exposed vaginal epithelia and pass infectious virus to CD4+ T cells without being productively infected themselves, and we point to a pathway that might enable HIV 1 to avoid degradation in vaginal LCs. Transport by migratory LCs to local lymphatics in a nonproductive but infectious form may aid HIV-1 in evasion of topical microbicides that target its intracellular productive life cycle. PMID- 21976647 TI - ISG56 and IFITM1 proteins inhibit hepatitis C virus replication. AB - Hepatitis C virus (HCV) often leads to persistent infection. Interferon (IFN) and IFN-stimulated genes (ISGs) are amplified during HCV infection but fail to eliminate virus from the liver in a large number of infected patients. We have observed previously that HCV infection induces IFN-beta production in immortalized human hepatocytes (IHH) as early as 24 h after infection, although virus replication is not inhibited. To gain insights on possible countermeasures of virus for the suppression of host antiviral response, the cellular transcriptional profiles of ISGs were examined after various treatments of IHH. The majority of ISGs were upregulated in IFN-treated IHH from the level for mock treated cells. However, the comparison of ISG expression in IFN-treated IHH and IFN-pretreated, HCV genotype 2a-infected IHH indicated that virus infection suppresses the upregulation of a subset of effector molecules, including ISG56 and IFITM1. Similar results were observed for HCV-infected Huh7 cells. Subsequent study suggested that the exogenous expression of ISG56 or IFITM1 inhibits HCV replication in IHH or Huh7 cells, and the knockdown of these genes enhanced HCV replication. Further characterization revealed that the overexpression of these ISGs does not block HCV pseudotype entry into Huh7 cells. Taken together, our results demonstrated that ISG56 and IFITM1 serve as important molecules to restrict HCV infection, and they may have implications in the development of therapeutic modalities. PMID- 21976646 TI - Indications that live poultry markets are a major source of human H5N1 influenza virus infection in China. AB - Human infections of H5N1 highly pathogenic avian influenza virus have continued to occur in China without corresponding outbreaks in poultry, and there is little conclusive evidence of the source of these infections. Seeking to identify the source of the human infections, we sequenced 31 H5N1 viruses isolated from humans in China (2005 to 2010). We found a number of viral genotypes, not all of which have similar known avian virus counterparts. Guided by patient questionnaire data, we also obtained environmental samples from live poultry markets and dwellings frequented by six individuals prior to disease onset (2008 and 2009). H5N1 viruses were isolated from 4 of the 6 live poultry markets sampled. In each case, the genetic sequences of the environmental and corresponding human isolates were highly similar, demonstrating a link between human infection and live poultry markets. Therefore, infection control measures in live poultry markets are likely to reduce human H5N1 infection in China. PMID- 21976648 TI - Cellular poly(c) binding proteins 1 and 2 interact with porcine reproductive and respiratory syndrome virus nonstructural protein 1beta and support viral replication. AB - Porcine reproductive and respiratory syndrome virus (PRRSV) infection of swine results in substantial economic losses to the swine industry worldwide. Identification of cellular factors involved in PRRSV life cycle not only will enable a better understanding of virus biology but also has the potential for the development of antiviral therapeutics. The PRRSV nonstructural protein 1 (nsp1) has been shown to be involved in at least two important functions in the infected hosts: (i) mediation of viral subgenomic (sg) mRNA transcription and (ii) suppression of the host's innate immune response mechanisms. To further our understanding of the role of the viral nsp1 in these processes, using nsp1beta, a proteolytically processed functional product of nsp1 as bait, we have identified the cellular poly(C)-binding proteins 1 and 2 (PCBP1 and PCBP2) as two of its interaction partners. The interactions of PCBP1 and PCBP2 with nsp1beta were confirmed both by coimmunoprecipitation in infected cells and/or in plasmid transfected cells and also by in vitro binding assays. During PRRSV infection of MARC-145 cells, the cytoplasmic PCBP1 and PCBP2 partially colocalize to the viral replication-transcription complexes. Furthermore, recombinant purified PCBP1 and PCBP2 were found to bind the viral 5' untranslated region (5'UTR). Small interfering RNA (siRNA)-mediated silencing of PCBP1 and PCBP2 in cells resulted in significantly reduced PRRSV genome replication and transcription without adverse effect on initial polyprotein synthesis. Overall, the results presented here point toward an important role for PCBP1 and PCBP2 in regulating PRRSV RNA synthesis. PMID- 21976650 TI - Spring-loaded model revisited: paramyxovirus fusion requires engagement of a receptor binding protein beyond initial triggering of the fusion protein. AB - During paramyxovirus entry into a host cell, receptor engagement by a specialized binding protein triggers conformational changes in the adjacent fusion protein (F), leading to fusion between the viral and cell membranes. According to the existing paradigm of paramyxovirus membrane fusion, the initial activation of F by the receptor binding protein sets off a spring-loaded mechanism whereby the F protein progresses independently through the subsequent steps in the fusion process, ending in membrane merger. For human parainfluenza virus type 3 (HPIV3), the receptor binding protein (hemagglutinin-neuraminidase [HN]) has three functions: receptor binding, receptor cleaving, and activating F. We report that continuous receptor engagement by HN activates F to advance through the series of structural rearrangements required for fusion. In contrast to the prevailing model, the role of HN-receptor engagement in the fusion process is required beyond an initiating step, i.e., it is still required even after the insertion of the fusion peptide into the target cell membrane, enabling F to mediate membrane merger. We also report that for Nipah virus, whose receptor binding protein has no receptor-cleaving activity, the continuous stimulation of the F protein by a receptor-engaged binding protein is key for fusion. We suggest a general model for paramyxovirus fusion activation in which receptor engagement plays an active role in F activation, and the continued engagement of the receptor binding protein is essential to F protein function until the onset of membrane merger. This model has broad implications for the mechanism of paramyxovirus fusion and for strategies to prevent viral entry. PMID- 21976651 TI - Microvesicles and viral infection. AB - Cells secrete various membrane-enclosed microvesicles from their cell surface (shedding microvesicles) and from internal, endosome-derived membranes (exosomes). Intriguingly, these vesicles have many characteristics in common with enveloped viruses, including biophysical properties, biogenesis, and uptake by cells. Recent discoveries describing the microvesicle-mediated intercellular transfer of functional cellular proteins, RNAs, and mRNAs have revealed additional similarities between viruses and cellular microvesicles. Apparent differences include the complexity of viral entry, temporally regulated viral expression, and self-replication proceeding to infection of new cells. Interestingly, many virally infected cells secrete microvesicles that differ in content from their virion counterparts but may contain various viral proteins and RNAs. For the most part, these particles have not been analyzed for their content or functions during viral infection. However, early studies of microvesicles (L particles) secreted from herpes simplex virus-infected cells provided the first evidence of microvesicle-mediated intercellular communication. In the case of Epstein-Barr virus, recent evidence suggests that this tumorigenic herpesvirus also utilizes exosomes as a mechanism of cell-to-cell communication through the transfer of signaling competent proteins and functional microRNAs to uninfected cells. This review focuses on aspects of the biology of microvesicles with an emphasis on their potential contributions to viral infection and pathogenesis. PMID- 21976652 TI - Phylogenetic analysis of H6 influenza viruses isolated from rosy-billed pochards (Netta peposaca) in Argentina reveals the presence of different HA gene clusters. AB - Until recently, influenza A viruses from wild waterfowl in South America were rarely isolated and/or characterized. To explore the ecology of influenza A viruses in this region, a long-term surveillance program was established in 2006 for resident and migratory water birds in Argentina. We report the characterization of 5 avian influenza viruses of the H6 hemagglutinin (HA) subtype isolated from rosy-billed pochards (Netta peposaca). Three of these viruses were paired to an N2 NA subtype, while the other two were of the N8 subtype. Genetic and phylogenetic analyses of the internal gene segments revealed a close relationship with influenza viruses from South America, forming a unique clade and supporting the notion of independent evolution from influenza A viruses in other latitudes. The presence of NS alleles A and B was also identified. The HA and NA genes formed unique clades separate from North American and Eurasian viruses, with the exception of the HA gene of one isolate, which was more closely related to the North American lineage, suggesting possible interactions between viruses of North American and South American lineages. Animal studies suggested that these Argentine H6 viruses could replicate and transmit inefficiently in chickens, indicating limited adaptation to poultry. Our results highlight the importance of continued influenza virus surveillance in wild birds of South America, especially considering the unique evolution of these viruses. PMID- 21976653 TI - A murine genital-challenge model is a sensitive measure of protective antibodies against human papillomavirus infection. AB - The available virus-like particle (VLP)-based prophylactic vaccines against specific human papillomavirus (HPV) types afford close to 100% protection against the type-associated lesions and disease. Based on papillomavirus animal models, it is likely that protection against genital lesions in humans is mediated by HPV type-restricted neutralizing antibodies that transudate or exudate at the sites of genital infection. However, a correlate of protection was not established in the clinical trials because few disease cases occurred, and true incident infection could not be reliably distinguished from the emergence or reactivation of prevalent infection. In addition, the current assays for measuring vaccine induced antibodies, even the gold standard HPV pseudovirion (PsV) in vitro neutralization assay, may not be sensitive enough to measure the minimum level of antibodies needed for protection. Here, we characterize the recently developed model of genital challenge with HPV PsV and determine the minimal amounts of VLP induced neutralizing antibodies that can afford protection from genital infection in vivo after transfer into recipient mice. Our data show that serum antibody levels >100-fold lower than those detectable by in vitro PsV neutralization assays are sufficient to confer protection against an HPV PsV genital infection in this model. The results clearly demonstrate that, remarkably, the in vivo assay is substantially more sensitive than in vitro PsV neutralization and thus may be better suited for studies to establish correlates of protection. PMID- 21976654 TI - Modeling of human cytomegalovirus maternal-fetal transmission in a novel decidual organ culture. AB - Human cytomegalovirus (HCMV) is the leading cause of congenital infection, associated with severe birth defects and intrauterine growth retardation. The mechanism of HCMV transmission via the maternal-fetal interface is largely unknown, and there are no animal models for HCMV. The initial stages of infection are believed to occur in the maternal decidua. Here we employed a novel decidual organ culture, using both clinically derived and laboratory-derived viral strains, for the ex vivo modeling of HCMV transmission in the maternal-fetal interface. Viral spread in the tissue was demonstrated by the progression of infected-cell foci, with a 1.3- to 2-log increase in HCMV DNA and RNA levels between days 2 and 9 postinfection, the expression of immediate-early and late proteins, the appearance of typical histopathological features of natural infection, and dose-dependent inhibition of infection by ganciclovir and acyclovir. HCMV infected a wide range of cells in the decidua, including invasive cytotrophoblasts, macrophages, and endothelial, decidual, and dendritic cells. Cell-to-cell viral spread was revealed by focal extension of infected-cell clusters, inability to recover infectious extracellular virus, and high relative proportions (88 to 93%) of cell-associated viral DNA. Intriguingly, neutralizing HCMV hyperimmune globulins exhibited inhibitory activity against viral spread in the decidua even when added at 24 h postinfection-providing a mechanistic basis for their clinical use in prenatal prevention. The ex vivo-infected decidual cultures offer unique insight into patterns of viral tropism and spread, defining initial stages of congenital HCMV transmission, and can facilitate evaluation of the effects of new antiviral interventions within the maternal-fetal interface milieu. PMID- 21976655 TI - The cytomegaloviral protein pUL138 acts as potentiator of tumor necrosis factor (TNF) receptor 1 surface density to enhance ULb'-encoded modulation of TNF-alpha signaling. AB - Human cytomegalovirus is a ubiquitous herpesvirus that establishes lifelong latent infection. Changes in immune homeostasis induce the reactivation of lytic infection, which is mostly inapparent in healthy individuals but often causes overt disease in immunocompromised hosts. Based on discrepant tumor necrosis factor receptor 1 surface disposition between human cytomegalovirus AD169 variants differing in the ULb' region, we identified the latency-associated gene product pUL138, which also is expressed during productive infection, as a selective potentiator of tumor necrosis factor receptor 1, one of the key receptors of innate immunity. Ectopically expressed pUL138 coprecipitated with tumor necrosis factor receptor 1, extended the protein half-life, and enhanced its signaling responses, thus leading to tumor necrosis factor receptor 1 hyperresponsiveness. Conversely, the targeted deletion of UL138 from the human cytomegaloviral genome strongly reduced tumor necrosis factor receptor 1 surface densities of infected cells. Remarkably, the comparison of UL138 deficiency to ULb' deficiency revealed the presence of further positive modulators of tumor necrosis factor alpha signal transduction encoded within the human cytomegalovirus ULb' region, identifying this region as a hub for multilayered tumor necrosis factor alpha signaling regulation. PMID- 21976656 TI - Rift Valley fever virus vaccine lacking the NSs and NSm genes is safe, nonteratogenic, and confers protection from viremia, pyrexia, and abortion following challenge in adult and pregnant sheep. AB - Rift Valley fever virus (RVFV) is a mosquito-borne human and veterinary pathogen causing large outbreaks of severe disease throughout Africa and the Arabian Peninsula. Safe and effective vaccines are critically needed, especially those that can be used in a targeted one-health approach to prevent both livestock and human disease. We report here on the safety, immunogenicity, and efficacy of the DeltaNSs-DeltaNSm recombinant RVFV (rRVFV) vaccine (which lacks the NSs and NSm virulence factors) in a total of 41 sheep, including 29 timed-pregnant ewes. This vaccine was proven safe and immunogenic for adult animals at doses ranging from 1.0 * 10(3) to 1.0 * 10(5) PFU administered subcutaneously (s.c.). Pregnant animals were vaccinated with 1.0 * 10(4) PFU s.c. at day 42 of gestation, when fetal sensitivity to RVFV vaccine-induced teratogenesis is highest. No febrile reactions, clinical illness, or pregnancy loss was observed following vaccination. Vaccination resulted in a rapid increase in anti-RVFV IgM (day 4) and IgG (day 7) titers. No seroconversion occurred in cohoused control animals. A subset of 20 ewes progressed to full-term delivery after vaccination. All lambs were born without musculoskeletal, neurological, or histological birth defects. Vaccine efficacy was assessed in 9 pregnant animals challenged at day 122 of gestation with virulent RVFV (1.0 * 10(6) PFU intravenously). Following challenge, 100% (9/9) of the animals were protected, progressed to full term, and delivered healthy lambs. As expected, all 3 sham-vaccinated controls experienced viremia, fetal death, and abortion postchallenge. These results demonstrate that the DeltaNSs-DeltaNSm rRVFV vaccine is safe and nonteratogenic and confers high level protection in sheep. PMID- 21976657 TI - Cardiotrophin-1 promotes a high survival rate in rabbits with lethal fulminant hepatitis of viral origin. AB - Rabbit hemorrhagic disease virus (RHDV) causes lethal fulminant hepatitis closely resembling acute liver failure (ALF) in humans. In this study, we investigated whether cardiotrophin-1 (CT-1), a cytokine with hepatoprotective properties, could attenuate liver damage and prolong survival in virus-induced ALF. Twenty four rabbits were infected with 2 * 10(4) hemagglutination units of RHDV. Twelve received five doses of CT-1 (100 MUg/kg) starting at 12 h postinfection (hpi) (the first three doses every 6 h and then two additional doses at 48 and 72 hpi), while the rest received saline. The animals were analyzed for survival, serum biochemistry, and viral load. Another cohort (n = 22) was infected and treated similarly, but animals were sacrificed at 30 and 36 hpi to analyze liver histology, viral load, and the expression of factors implicated in liver damage and repair. All infected rabbits that received saline died by 60 hpi, while 67% of the CT-1-treated animals survived until the end of the study. Treated animals showed improved liver function and histology, while the viral loads were similar. In the livers of CT-1-treated rabbits we observed reduction of oxidative stress, diminished PARP1/2 and JNK activation, and decreased inflammatory reaction, as reflected by reduced expression of tumor necrosis factor alpha, interleukin 1beta, Toll-like receptor 4, VCAM-1, and MMP-9. In addition, CT-1-treated rabbits exhibited marked upregulation of TIMP-1 and increased expression of cytoprotective and proregenerative growth factors, including platelet-derived growth factor B, epidermal growth factor, platelet-derived growth factor receptor beta, and c-Met. In conclusion, in a lethal form of acute viral hepatitis, CT-1 increases animal survival by attenuating inflammation and activating cytoprotective mechanisms, thus representing a promising therapy for ALF of viral origin. PMID- 21976658 TI - Infection with seasonal influenza virus elicits CD4 T cells specific for genetically conserved epitopes that can be rapidly mobilized for protective immunity to pandemic H1N1 influenza virus. AB - In recent years, influenza viruses with pandemic potential have been a major concern worldwide. One unresolved issue is how infection or vaccination with seasonal influenza virus strains influences the ability to mount a protective immune response to novel pandemic strains. In this study, we developed a mouse model of primary and secondary influenza infection by using a widely circulating seasonal H1N1 virus and the pandemic strain of H1N1 that emerged in Mexico in 2009, and we evaluated several key issues. First, using overlapping peptide libraries encompassing the entire translated sequences of 5 major influenza virus proteins, we assessed the specificity of CD4 T cell reactivity toward epitopes conserved among H1N1 viruses or unique to the seasonal or pandemic strain by enzyme-linked immunospot (ELISpot) assays. Our data show that CD4 T cells reactive to both virus-specific and genetically conserved epitopes are elicited, allowing separate tracking of these responses. Populations of cross-reactive CD4 T cells generated from seasonal influenza infection were found to expand earlier after secondary infection with the pandemic H1N1 virus than CD4 T cell populations specific for new epitopes. Coincident with this rapid CD4 T cell response was a potentiated neutralizing-antibody response to the pandemic strain and protection from the pathological effects of infection with the pandemic virus. This protection was not dependent on CD8 T cells. Together, our results indicate that exposure to seasonal vaccines and infection elicits CD4 T cells that promote the ability of the mammalian host to mount a protective immune response to pandemic strains of influenza virus. PMID- 21976660 TI - Assessment of a rapid referral pathway for suspected colorectal cancer in Madrid. AB - OBJECTIVE: To assess the results achieved with a rapid referral pathway for suspected colorectal cancer (CRC), comparing with the standard referral pathway. METHODS: Three-year audit of patients suspected of having CRC routed via a rapid referral pathway, and patients with CRC routed via the standard referral pathway of a health care district serving a population of 498,000 in Madrid (Spain). Outcomes included referral criteria met, waiting times, cancer diagnosed and stage of disease. RESULTS: Two hundred and seventy-two patients (mean age 68.8 years, SD 14.0; 51% male) were routed via the rapid referral pathway for colonoscopy. Seventy-nine per cent of referrals fulfilled the criteria for high risk of CRC. Fifty-two cancers were diagnosed: 26% Stage A (Astler-Coller), 36% Stage B, 24% Stage C and 14% Stage D. Average waiting time to colonoscopy for the rapid referral patients was 18.5 days (SD 19.1) and average waiting time to surgery was 28.6 days (SD 23.9). Colonoscopy was performed within 15 days in 65% of CRC rapid referral patients compared to 43% of standard pathway patients (P = 0.004). Overall waiting time for patients with CRC in the rapid referral pathway was 52.7 days (SD 32.9); while for those in the standard pathway, it was 71.5 days (SD 57.4) (P = 0.002). Twenty-six per cent Stage A CRC was diagnosed in the rapid referral pathway compared to 12% in the standard pathway (P < 0.001). CONCLUSION: The rapid referral pathway reduced waiting time to colonoscopy and overall waiting time to final treatment and appears to be an effective strategy for diagnosing CRC in its early stages. PMID- 21976661 TI - Public knowledge of the symptoms of myocardial infarction: a street survey in Birmingham, England. AB - BACKGROUND: Myocardial infarction (MI) is a leading cause of death in the UK. A good clinical outcome depends on rapid treatment following the onset of symptoms. A person's knowledge of typical symptoms determines how quickly they present to the medical services. OBJECTIVES: To investigate knowledge of MI symptoms among the general population and the relationship between age, gender and socio economic status with knowledge. METHODS: Street survey of 302 participants in Birmingham, UK, using an interviewer-assisted questionnaire. RESULTS: Of seven symptoms accepted in the medical literature as typical of an MI, central chest pain was the most frequently identified (75% of the sample), followed by arm pain or numbness (40%), shortness of breath (35%), fainting or dizziness (21%) and sweating (21%). Feeling or being sick and neck or jaw pain were mentioned by 8.1% and 5.9%, respectively, while an atypical or inapplicable symptom, collapse (9.9%) was mentioned more often than these. Over half the sample knew only two or fewer MI symptoms. The mean number of typical symptoms identified was 2.2 (SD = 1.28). Respondents from professional occupations and those with previous experience of MI, whether direct or indirect, showed better awareness. CONCLUSIONS: The study demonstrated a paucity of knowledge of MI symptoms among the general public. Such findings provide a baseline to guide public health campaigns targeting awareness of MI. PMID- 21976659 TI - Coagulation factor IX mediates serotype-specific binding of species A adenoviruses to host cells. AB - Human species A adenoviruses (HAdVs) comprise three serotypes: HAdV-12, -18, and 31. These viruses are common pathogens and cause systemic infections that usually involve the airways and/or intestine. In immunocompromised individuals, species A adenoviruses in general, and HAdV-31 in particular, cause life-threatening infections. By combining binding and infection experiments, we demonstrate that coagulation factor IX (FIX) efficiently enhances binding and infection by HAdV-18 and HAdV-31, but not by HAdV-12, in epithelial cells originating from the airways or intestine. This is markedly different from the mechanism for HAdV-5 and other human adenoviruses, which utilize coagulation factor X (FX) for infection of host cells. Surface plasmon resonance experiments revealed that the affinity of the HAdV-31 hexon-FIX interaction is higher than that of the HAdV-5 hexon-FX interaction and that the half-lives of these interactions are profoundly different. Moreover, both HAdV-31-FIX and HAdV-5-FX complexes bind to heparan sulfate-containing glycosaminoglycans (GAGs) on target cells, but binding studies utilizing cells expressing specific GAGs and GAG-cleaving enzymes revealed differences in GAG dependence and specificity between these two complexes. These findings add to our understanding of the intricate infection pathways used by human adenoviruses, and they may contribute to better design of HAdV-based vectors for gene and cancer therapy. Furthermore, the interaction between the HAdV-31 hexon and FIX may also serve as a target for antiviral treatment. PMID- 21976662 TI - Effects of extracellular DNA on plasminogen activation and fibrinolysis. AB - The increased levels of extracellular DNA found in a number of disorders involving dysregulation of the fibrinolytic system may affect interactions between fibrinolytic enzymes and inhibitors. Double-stranded (ds) DNA and oligonucleotides bind tissue-(tPA) and urokinase (uPA)-type plasminogen activators, plasmin, and plasminogen with submicromolar affinity. The binding of enzymes to DNA was detected by EMSA, steady-state, and stopped-flow fluorimetry. The interaction of dsDNA/oligonucleotides with tPA and uPA includes a fast bimolecular step, followed by two monomolecular steps, likely indicating slow conformational changes in the enzyme. DNA (0.1-5.0 MUg/ml), but not RNA, potentiates the activation of Glu- and Lys-plasminogen by tPA and uPA by 480- and 70-fold and 10.7- and 17-fold, respectively, via a template mechanism similar to that known for fibrin. However, unlike fibrin, dsDNA/oligonucleotides moderately affect the reaction between plasmin and alpha(2)-antiplasmin and accelerate the inactivation of tPA and two chain uPA by plasminogen activator inhibitor-1 (PAI 1), which is potentiated by vitronectin. dsDNA (0.1-1.0 MUg/ml) does not affect the rate of fibrinolysis by plasmin but increases by 4-5-fold the rate of fibrinolysis by Glu-plasminogen/plasminogen activator. The presence of alpha(2) antiplasmin abolishes the potentiation of fibrinolysis by dsDNA. At higher concentrations (1.0-20 MUg/ml), dsDNA competes for plasmin with fibrin and decreases the rate of fibrinolysis. dsDNA/oligonucleotides incorporated into a fibrin film also inhibit fibrinolysis. Thus, extracellular DNA at physiological concentrations may potentiate fibrinolysis by stimulating fibrin-independent plasminogen activation. Conversely, DNA could inhibit fibrinolysis by increasing the susceptibility of fibrinolytic enzymes to serpins. PMID- 21976663 TI - Role for the terminal clasp of HIV-1 gp41 glycoprotein in the initiation of membrane fusion. AB - The binding by HIV-1 gp120 to CD4 and a chemokine receptor activates the membrane fusion glycoprotein, gp41. The fusion function of gp41 involves the refolding of its core into a 6-helix bundle, which apposes the lipophilic termini (the fusion peptide and transmembrane domain) and the associated cell and viral membranes, leading to their fusion. In this study, we examined the functional role of the polar segment and membrane proximal external region (MPER), which link the fusion peptide and transmembrane domain, respectively, to the core domain and interact to form a terminal clasp adjacent to the core. Limited proteolysis indicated that the terminal clasp is destabilized by simultaneous I535A/V539G mutations within the polar segment and mutations within the MPER. The destabilizing effects of I535A/V539G correlated with defective cell-cell fusion, viral entry, and viral replication. By using lipophilic and cytoplasmic fluorescent dye transfer assays, we found that terminal clasp destabilization is linked to a block in the lipid mixing/hemifusion phase of the membrane fusion cascade. Because the biosynthesis of the prefusion gp120-gp41 complex did not appear to be affected by I535A/V539G, we infer that the hemifusion block is due to a specific effect on the trimer of hairpins conformation of gp41. By contrast, the decreased fusion function of the MPER mutants correlated with a decrease in the interfacial hydropathy of the MPER sequence, suggesting that the prefusion Env complex had been adversely affected in these cases. These findings reveal a novel conserved functional target for the discovery of fusion inhibitors. PMID- 21976664 TI - Using quantitative redox proteomics to dissect the yeast redoxome. AB - To understand and eventually predict the effects of changing redox conditions and oxidant levels on the physiology of an organism, it is essential to gain knowledge about its redoxome: the proteins whose activities are controlled by the oxidation status of their cysteine thiols. Here, we applied the quantitative redox proteomic method OxICAT to Saccharomyces cerevisiae and determined the in vivo thiol oxidation status of almost 300 different yeast proteins distributed among various cellular compartments. We found that a substantial number of cytosolic and mitochondrial proteins are partially oxidized during exponential growth. Our results suggest that prevailing redox conditions constantly control central cellular pathways by fine-tuning oxidation status and hence activity of these proteins. Treatment with sublethal H(2)O(2) concentrations caused a subset of 41 proteins to undergo substantial thiol modifications, thereby affecting a variety of different cellular pathways, many of which are directly or indirectly involved in increasing oxidative stress resistance. Classification of the identified protein thiols according to their steady-state oxidation levels and sensitivity to peroxide treatment revealed that redox sensitivity of protein thiols does not predict peroxide sensitivity. Our studies provide experimental evidence that the ability of protein thiols to react to changing peroxide levels is likely governed by both thermodynamic and kinetic parameters, making predicting thiol modifications challenging and de novo identification of peroxide sensitive protein thiols indispensable. PMID- 21976665 TI - Uncoupling of Pyrin-only protein 2 (POP2)-mediated dual regulation of NF-kappaB and the inflammasome. AB - Activation of transcription factor NF-kappaB and inflammasome-directed caspase-1 cleavage of IL-1beta are key processes in the inflammatory response to pathogen or host-derived signals. Pyrin-only proteins (POPs) are restricted to Old World monkeys, apes, and humans and have previously been shown to impair inflammasome assembly and/or NF-kappaB p65 transcriptional activity in transfected epithelial cells. However, the biological role of POP2 and the molecular basis for its observed functions are not well understood. In this report we demonstrate that POP2 regulates TNFalpha and IL-1beta responses in human monocytic THP-1 cells and in stable transfectants of mouse J774A.1 macrophages. Deletion analysis of POP2 revealed that the first alpha-helix (residues 1-19) is necessary and sufficient for both inflammasome and NF-kappaB inhibitory functions. Further, key acidic residues Glu(6), Asp(8), and Glu(16), believed critical for Pyrin/Pyrin domain interaction, are important for inflammasome inhibition. Moreover, these mutations did not reduce the effect of POP2 upon NF-kappaB, indicating that the inflammasome and NF-kappaB inhibitory properties of POP2 can be uncoupled mechanistically. Collectively, these data demonstrate that POP2 acts as a regulator of inflammatory signals and exerts its two known functions through distinct modalities employed by its first alpha-helix. PMID- 21976666 TI - Activating transcription factor 6 limits intracellular accumulation of mutant alpha(1)-antitrypsin Z and mitochondrial damage in hepatoma cells. AB - alpha(1)-Antitrypsin is a serine protease inhibitor secreted by hepatocytes. A variant of alpha(1)-antitrypsin with an E342K (Z) mutation (ATZ) has propensity to form polymers, is retained in the endoplasmic reticulum (ER), is degraded by both ER-associated degradation and autophagy, and causes hepatocyte loss. Constant features in hepatocytes of PiZZ individuals and in PiZ transgenic mice expressing ATZ are the formation of membrane-limited globular inclusions containing ATZ and mitochondrial damage. Expression of ATZ in the liver does not induce the unfolded protein response (UPR), a protective mechanism aimed to maintain ER homeostasis in the face of an increased load of proteins. Here we found that in hepatoma cells the ER E3 ligase HRD1 functioned to degrade most of the ATZ before globular inclusions are formed. Activation of the activating transcription factor 6 (ATF6) branch of the UPR by expression of spliced ATF6(1 373) decreased intracellular accumulation of ATZ and the formation of globular inclusions by a pathway that required HRD1 and the proteasome. Expression of ATF6(1-373) in ATZ-expressing hepatoma cells did not induce autophagy and increased the level of the proapoptotic factor CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) but did not lead to apoptotic DNA fragmentation. Expression of ATF6(1-373) did not cause inhibition of protein synthesis and prevented mitochondrial damage induced by ATZ expression. It was concluded that activation of the ATF6 pathway of the UPR limits ATZ-dependent cell toxicity by selectively promoting ER-associated degradation of ATZ and is thereby a potential target to prevent hepatocyte loss in addition to autophagy enhancing drugs. PMID- 21976667 TI - Nitric oxide suppresses tumor cell migration through N-Myc downstream-regulated gene-1 (NDRG1) expression: role of chelatable iron. AB - N-Myc downstream-regulated gene 1 (NDRG1) is a ubiquitous cellular protein that is up-regulated under a multitude of stress and growth-regulatory conditions. Although the exact cellular functions of this protein have not been elucidated, mutations in this gene or aberrant expression of this protein have been linked to both tumor suppressive and oncogenic phenotypes. Previous reports have demonstrated that NDRG1 is strongly up-regulated by chemical iron chelators and hypoxia, yet its regulation by the free radical nitric oxide ((*)NO) has never been demonstrated. Herein, we examine the chemical biology that confers NDRG1 responsiveness at the mRNA and protein levels to (*)NO. We demonstrate that the interaction of (*)NO with the chelatable iron pool (CIP) and the appearance of dinitrosyliron complexes (DNIC) are key determinants. Using HCC 1806 triple negative breast cancer cells, we find that NDRG1 is up-regulated by physiological (*)NO concentrations in a dose- and time-dependant manner. Tumor cell migration was suppressed by NDRG1 expression and we excluded the involvement of HIF-1alpha, sGC, N-Myc, and c-Myc as upstream regulatory targets of (*)NO. Augmenting the chelatable iron pool abolished (*)NO-mediated NDRG1 expression and the associated phenotypic effects. These data, in summary, reveal a link between (*)NO, chelatable iron, and regulation of NDRG1 expression and signaling in tumor cells. PMID- 21976668 TI - Cytochrome P450 is present in both ferrous and ferric forms in the resting state within intact Escherichia coli and hepatocytes. AB - Cytochrome P450 enzymes (P450s) are exceptionally versatile monooxygenases, mediating hydroxylations of unactivated C-H bonds, epoxidations, dealkylations, and N- and S-oxidations as well as other less common reactions. In the conventional view of the catalytic cycle, based upon studies of P450s in vitro, substrate binding to the Fe(III) resting state facilitates the first 1-electron reduction of the heme. However, the resting state of P450s in vivo has not been examined. In the present study, whole cell difference spectroscopy of bacterial (CYP101A1 and CYP176A1, i.e. P450cam and P450cin) and mammalian (CYP1A2, CYP2C9, CYP2A6, CYP2C19, and CYP3A4) P450s expressed within intact Escherichia coli revealed that both Fe(III) and Fe(II) forms of the enzyme are present in the absence of substrates. The relevance of this finding was supported by similar observations of Fe(II) P450 heme in intact rat hepatocytes. Electron paramagnetic resonance (EPR) spectroscopy of the bacterial forms in intact cells showed that a proportion of the P450 in cells was in an EPR-silent form in the native state consistent with the presence of Fe(II) P450. Coexpression of suitable cognate electron donors increased the degree of endogenous reduction to over 80%. A significant proportion of intracellular P450 remained in the Fe(II) form after vigorous aeration of cells. The addition of substrates increased the proportion of Fe(II) heme, suggesting a kinetic gate to heme reduction in the absence of substrate. In summary, these observations suggest that the resting state of P450s should be regarded as a mixture of Fe(III) and Fe(II) forms in both aerobic and oxygen-limited conditions. PMID- 21976669 TI - Association of plasminogen activator inhibitor type 2 (PAI-2) with proteasome within endothelial cells activated with inflammatory stimuli. AB - Quiescent endothelial cells contain low concentrations of plasminogen activator inhibitor type 2 (PAI-2). However, its synthesis can be rapidly stimulated by a variety of inflammatory mediators. In this study, we provide evidence that PAI-2 interacts with proteasome and affects its activity in endothelial cells. To ensure that the PAI-2.proteasome complex is formed in vivo, both proteins were coimmunoprecipitated from endothelial cells and identified with specific antibodies. The specificity of this interaction was evidenced after (a) transfection of HeLa cells with pCMV-PAI-2 and coimmunoprecipitation of both proteins with anti-PAI-2 antibodies and (b) silencing of the PAI-2 gene using specific small interfering RNA (siRNA). Subsequently, cellular distribution of the PAI-2.proteasome complexes was established by immunogold staining and electron microscopy analyses. As judged by confocal microscopy, both proteins appeared in a diffuse cytosolic pattern, but they also could be found in a dense perinuclear and nuclear location. PAI-2 was not polyubiquitinated, suggesting that it bound to proteasome not as the substrate but rather as its inhibitor. Consistently, increased PAI-2 expression (a) abrogated degradation of degron analyzed after cotransfection of HeLa cells with pCMV-PAI-2 and pd2EGFP-N1, (b) prevented degradation of p53, as evidenced both by confocal microscopy and Western immunoblotting, and (c) inhibited proteasome cleavage of specific fluorogenic substrate. This suggests that PAI-2, in endothelial cells induced with inflammatory stimuli, can inhibit proteasome and thus tilt the balance favoring proapoptotic signaling. PMID- 21976670 TI - PEX5 protein binds monomeric catalase blocking its tetramerization and releases it upon binding the N-terminal domain of PEX14. AB - Newly synthesized peroxisomal matrix proteins are targeted to the organelle by PEX5. PEX5 has a dual role in this process. First, it acts as a soluble receptor recognizing these proteins in the cytosol. Subsequently, at the peroxisomal docking/translocation machinery, PEX5 promotes their translocation across the organelle membrane. Despite significant advances made in recent years, several aspects of this pathway remain unclear. Two important ones regard the formation and disruption of the PEX5-cargo protein interaction in the cytosol and at the docking/translocation machinery, respectively. Here, we provide data on the interaction of PEX5 with catalase, a homotetrameric enzyme in its native state. We found that PEX5 interacts with monomeric catalase yielding a stable protein complex; no such complex was detected with tetrameric catalase. Binding of PEX5 to monomeric catalase potently inhibits its tetramerization, a property that depends on domains present in both the N- and C-terminal halves of PEX5. Interestingly, the PEX5-catalase interaction is disrupted by the N-terminal domain of PEX14, a component of the docking/translocation machinery. One or two of the seven PEX14-binding diaromatic motifs present in the N-terminal half of PEX5 are probably involved in this phenomenon. These results suggest the following: 1) catalase domain(s) involved in the interaction with PEX5 are no longer accessible upon tetramerization of the enzyme; 2) the catalase-binding interface in PEX5 is not restricted to its C-terminal peroxisomal targeting sequence type 1-binding domain and also involves PEX5 N-terminal domain(s); and 3) PEX14 participates in the cargo protein release step. PMID- 21976671 TI - Brainstem deficiency of the 14-3-3 regulator of serotonin synthesis: a proteomics analysis in the sudden infant death syndrome. AB - Impaired brainstem responses to homeostatic challenges during sleep may result in the sudden infant death syndrome (SIDS). Previously we reported a deficiency of serotonin (5-HT) and its key biosynthetic enzyme, tryptophan hydroxylase (TPH2), in SIDS infants in the medullary 5-HT system that modulates homeostatic responses during sleep. Yet, the underlying basis of the TPH2 and 5-HT deficiency is unknown. In this study, we tested the hypothesis that proteomics would uncover previously unrecognized abnormal levels of proteins related to TPH2 and 5-HT regulation in SIDS cases compared with controls, which could provide novel insight into the basis of their deficiency. We first performed a discovery proteomic analysis of the gigantocellularis of the medullary 5-HT system in the same data set with deficiencies of TPH2 and 5-HT levels. Analysis in 6 SIDS cases and 4 controls revealed a 42-75% reduction in abundance in 5 of the 6 isoforms identified of the 14-3-3 signal transduction family, which is known to influence TPH2 activity (p < 0.07). These findings were corroborated in an additional SIDS and control sample using an orthogonal MS(E)-based quantitative proteomic strategy. To confirm these proteomics results in a larger data set (38 SIDS, 11 controls), we applied Western blot analysis in the gigantocellularis and found that 4/7 14-3-3 isoforms identified were significantly reduced in SIDS cases (p <= 0.02), with a 43% reduction in all 14-3-3 isoforms combined (p < 0.001). Abnormalities in 5-HT and TPH2 levels and 5-HT(1A) receptor binding were associated with the 14-3-3 deficits in the same SIDS cases. These data suggest a potential molecular defect in SIDS related to TPH2 regulation, as 14-3-3 is critical in this process. PMID- 21976672 TI - Phase 1/2 study to assess the safety, efficacy, and pharmacokinetics of barasertib (AZD1152) in patients with advanced acute myeloid leukemia. AB - The primary objective of this 2-part phase 1/2 study was to determine the maximum tolerated dose (MTD) of the potent and selective Aurora B kinase inhibitor barasertib (AZD1152) in patients with newly diagnosed or relapsed acute myeloid leukemia (AML). Part A determined the MTD of barasertib administered as a continuous 7-day infusion every 21 days. In part B, the efficacy of barasertib was evaluated at the MTD. In part A, 32 patients were treated with barasertib 50 mg (n = 3), 100 mg (n = 3), 200 mg (n = 3), 400 mg (n = 4), 800 mg (n = 7), 1200 mg (n = 6), and 1600 mg (n = 6). Dose-limiting toxicities (stomatitis/mucosal inflammation events) were reported in the 800 mg (n = 1), 1200 mg (n = 1), and 1600 mg (n = 2) groups. The MTD was defined as 1200 mg. In part B, 32 patients received barasertib 1200 mg. In each part of the study, 8 of 32 patients had a hematologic response according to Cheson AML criteria. The most commonly reported grade >= 3 events were febrile neutropenia (n = 24) and stomatitis/mucosal inflammation (n = 16). We concluded that the MTD of barasertib is 1200 mg in patients with relapsed or newly diagnosed AML. Toxicity was manageable and barasertib treatment resulted in an overall hematologic response rate of 25%. This study is registered at www.ClinicalTrials.gov as NCT00497991. PMID- 21976673 TI - Incidence and predictors of congestive heart failure after autologous hematopoietic cell transplantation. AB - Advances in autologous hematopoietic cell transplantation (HCT) strategies have resulted in a growing number of long-term survivors. However, these survivors are at increased risk of developing cardiovascular complications due to pre-HCT therapeutic exposures and conditioning and post-HCT comorbidities. We examined the incidence and predictors of congestive heart failure (CHF) in 1244 patients undergoing autologous HCT for a hematologic malignancy between 1988 and 2002. The cumulative incidence of CHF was 4.8% at 5 years and increased to 9.1% at 15 years after transplantation; the CI for female lymphoma survivors was 14.5% at 15 years. The cohort was at a 4.5-fold increased risk of CHF (standardized incidence ratio = 4.5), compared with the general population. The risk of CHF increased substantially for patients receiving >= 250 mg/m(2) of cumulative anthracycline exposure (odds ratio [OR]: 9.9, P < .01), creating a new and lower threshold for cardiac surveillance after HCT. The presence of hypertension among recipients of high-dose anthracycline (>= 250 mg/m(2)) resulted in a 35-fold risk (OR: 35.3, P < .01) of CHF; the risk was nearly 27-fold (OR: 26.8, P < .01) for high-dose anthracycline recipients with diabetes, providing evidence that hypertension and diabetes may be critical modifiers of anthracycline-related myocardial injury after HCT and creating targeted populations for aggressive intervention. PMID- 21976675 TI - Rac regulates PtdInsP3 signaling and the chemotactic compass through a redox mediated feedback loop. AB - Directional cell migration is an essential requirement for efficient neutrophil translocation to sites of infection and requires the establishment of a polarized cell characterized by an actin-rich leading edge facing the chemoattractant gradient. The asymmetrical accumulation of phosphatidylinositol(3,4,5) trisphosphate [PtdIns(3,4,5)P(3)] in the up-gradient leading edge is a hallmark of polarization and regulates the recruitment and localization of various effector proteins at the leading-edge plasma membrane. How shallow gradients of chemoattractants trigger and maintain a much steeper intracellular gradient of PtdIns(3,4,5)P(3) is a critical question in the study of leukocyte chemotaxis. Our data demonstrate that the migration of neutrophils toward the chemoattractant N-formyl-L-methionyl-L-leucyl-L-phenylalanine depends on the generation of reactive oxygen species by the phagocytic NADPH oxidase (NOX2) and subsequent oxidation and inhibition of phosphatase and tensin homolog. Moreover, we show that events downstream of PtdIns(3,4,5)P(3), including phosphorylation of AKT, Rac activation, uncapping of actin filaments, and directional migration, can be attenuated by ROS scavengers or genetic ablation of NOX2. Using Rac mutants that are defective in their ability to activate NOX2, we show that Rac regulates a redox-mediated feedback loop that mediates directional migration of neutrophils. PMID- 21976674 TI - Reduced-intensity conditioning with combined haploidentical and cord blood transplantation results in rapid engraftment, low GVHD, and durable remissions. AB - We conducted a 45 patient prospective study of reduced-intensity conditioning (RIC) and transplantation of unrelated umbilical cord blood (UCB) and CD34(+) stem cells from a haploidentical family member. Median age was 50 years; weight was 80 kg. Fifty-eight percent had active disease. Neutrophil engraftment occurred at 11 days (interquartile range [IQR], 9-15) and platelet engraftment at 19 days (IQR, 15-33). In the majority of patients, early haploidentical engraftment was replaced by durable engraftment of UCB by 100 days, with regular persistence of minor host and/or haplo-hematopoiesis. Percentage of haplochimerism at day 100 correlated with the haplo-CD34 dose (P = .003). Cumulative incidence of acute GVHD (aGVHD) was 25% and chronic GVHD (cGVHD) was 5%. Actuarial survival at 1 year was 55%, progression-free survival (PFS) was 42%, nonrelapse mortality (NRM) was 28%, and relapse was 30%. RIC and haplo-cord transplantation results in fast engraftment of neutrophils and platelets, low incidences of aGVHD and cGVHD, low frequency of delayed opportunistic infections, reduced transfusion requirements, shortened length of hospital stay, and promising long-term outcomes. UCB cell dose had no impact on time to hematopoietic recovery. Therefore, UCB selection can prioritize matching, and better matched donors can be identified rapidly for most patients. This study is registered at http://clinicaltrials.gov as NCI clinical trial no. NCT00943800. PMID- 21976676 TI - Epigenetic inactivation of the MIR34B/C in multiple myeloma. AB - We postulated that MIR34B/C, a direct transcriptional target of TP53, might be inactivated by promoter hypermethylation in multiple myeloma (MM). MIR34B/C promoter methylation was studied in 8 normal marrow controls, 8 MM cell lines, 95 diagnostic, and 23 relapsed/progressed MM samples by methylation-specific PCR. MIR34B/C was methylated in 6 (75.0%) MM cell lines but not normal controls. 5-Aza 2'-deoxycytidine led to MIR34B/C promoter demethylation and MIR34B reexpression. Moreover, restoration of MIR34B led to reduced cellular proliferation and enhanced apoptosis of myeloma cells. In primary samples, methylation of MIR34B/C occurred in 5.3% at diagnosis and 52.2% at relapse/disease progression (P < .001). In 12 MM patients with paired samples at diagnosis and relapse/progression, MIR34B/C methylation was acquired in 6 at relapse/progression. In conclusion, MIR34B/C is a tumor suppressor in myeloma. Hypermethylation of MIR34B/C is tumor-specific. Frequent MIR34B/C hypermethylation during relapse/progression but not at diagnosis implicated a role of MIR34B/C hypermethylation in myeloma relapse/progression. PMID- 21976677 TI - Polyphosphate is a cofactor for the activation of factor XI by thrombin. AB - Factor XI deficiency is associated with a bleeding diathesis, but factor XII deficiency is not, indicating that, in normal hemostasis, factor XI must be activated in vivo by a protease other than factor XIIa. Several groups have identified thrombin as the most likely activator of factor XI, although this reaction is slow in solution. Although certain nonphysiologic anionic polymers and surfaces have been shown to enhance factor XI activation by thrombin, the physiologic cofactor for this reaction is uncertain. Activated platelets secrete the highly anionic polymer polyphosphate, and our previous studies have shown that polyphosphate has potent procoagulant activity. We now report that polyphosphate potently accelerates factor XI activation by alpha-thrombin, beta thrombin, and factor XIa and that these reactions are supported by polyphosphate polymers of the size secreted by activated human platelets. We therefore propose that polyphosphate is a natural cofactor for factor XI activation in plasma that may help explain the role of factor XI in hemostasis and thrombosis. PMID- 21976678 TI - Mutation of the gastric hydrogen-potassium ATPase alpha subunit causes iron deficiency anemia in mice. AB - Iron is an essential component of heme and hemoglobin, and therefore restriction of iron availability directly limits erythropoiesis. In the present study, we report a defect in iron absorption that results in iron-deficiency anemia, as revealed by an N-ethyl-N-nitrosourea-induced mouse phenotype called sublytic. Homozygous sublytic mice develop hypochromic microcytic anemia with reduced osmotic fragility of RBCs. The sublytic phenotype stems from impaired gastrointestinal iron absorption caused by a point mutation of the gastric hydrogen-potassium ATPase alpha subunit encoded by Atp4a, which results in achlorhydria. The anemia of sublytic homozygotes can be corrected by feeding with a high-iron diet or by parenteral injection of iron dextran; rescue can also be achieved by providing acidified drinking water to sublytic homozygotes. These findings establish the necessity of the gastric proton pump for iron absorption and effective erythropoiesis. PMID- 21976679 TI - cAMP-responsive element modulator (CREM)alpha protein signaling mediates epigenetic remodeling of the human interleukin-2 gene: implications in systemic lupus erythematosus. AB - IL-2 is a key cytokine during proliferation and activation of T lymphocytes and functions as an auto- and paracrine growth factor. Regardless of activating effects on T lymphocytes, the absence of IL-2 has been linked to the development of autoimmune pathology in mice and humans. Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease and characterized by dysregulation of lymphocyte function, transcription factor and cytokine expression, and antigen presentation. Reduced IL-2 expression is a hallmark of SLE T lymphocytes and results in decreased numbers of regulatory T lymphocytes which play an important role in preventing autoimmunity. Reduced IL-2 expression was linked to overproduction of the transcription regulatory factor cAMP-responsive element modulator (CREM)alpha in SLE T lymphocytes and subsequent CREMalpha binding to a CRE site within the IL2 promoter (-180 CRE). In this study, we demonstrate the involvement of CREMalpha-mediated IL2 silencing in T lymphocytes from SLE patients through a gene-wide histone deacetylase 1-directed deacetylation of histone H3K18 and DNA methyltransferase 3a-directed cytosine phosphate guanosine (CpG)-DNA hypermethylation. For the first time, we provide direct evidence that CREMalpha mediates silencing of the IL2 gene in SLE T cells though histone deacetylation and CpG-DNA methylation. PMID- 21976680 TI - The CD24 protein inducible expression system is an ideal tool to explore the potential of CD24 as an oncogene and a target for immunotherapy in vitro and in vivo. AB - CD24 is a cell surface, heavily glycosylated glycosylphosphatidylinositol anchored mucin-like protein that is overexpressed in various human malignancies. To accurately analyze CD24 function and dissect its biological role in a defined genetic background, it is critical to tightly regulate its expression and be able to turn it on/off in a restricted environment and at a specific time. The tetracycline-induced expression system is most promising as it exhibits such regulation, lack of pleiotropic effects, and high and rapid induction levels. To evaluate the oncogenic and immunotherapeutic potential of CD24 by applying the Tet-On system, the human CD24 gene was cloned downstream to two tetracycline operator sequences, resulting in pCDNA4/TO-CD24, which was then transfected into tetracycline (Tet) repressor-expressing cells (293T-REx), allowing tight on/off regulation, thereby resulting in a very low background or leaky CD24 expression. Selected clones were chosen for further studies and characterized in vitro and in vivo, and several treatment modalities were examined. In addition, the role of CD24 in promoting cell proliferation and tumor growth was studied. The tetracycline-dependent system was successfully implemented. Tetracycline treatment induced CD24 expression in a dose- and time-dependent fashion, which was abrogated following treatment with anti-CD24 monoclonal antibodies (mAbs). CD24-induced expression led to an increased proliferation rate that was inhibited by mAb treatment. In vivo, significantly larger tumors were developed in tetracycline-fed mice. The CD24 Tet-On system is a good model to unravel the role and underlying CD24 pathogenesis in vivo. This valuable tool allows the successful study of novel treatment options, whose effectiveness depends on the CD24 expression level. This set of experiments supports CD24 oncogenic properties. PMID- 21976682 TI - Tagetitoxin inhibits RNA polymerase through trapping of the trigger loop. AB - Tagetitoxin (Tgt) inhibits multisubunit chloroplast, bacterial, and some eukaryotic RNA polymerases (RNAPs). A crystallographic structure of Tgt bound to bacterial RNAP apoenzyme shows that Tgt binds near the active site but does not explain why Tgt acts only at certain sites. To understand the Tgt mechanism, we constructed a structural model of Tgt bound to the transcription elongation complex. In this model, Tgt interacts with the beta' subunit trigger loop (TL), stabilizing it in an inactive conformation. We show that (i) substitutions of the Arg residue of TL contacted by Tgt confer resistance to inhibitor; (ii) Tgt inhibits RNAP translocation, which requires TL movements; and (iii) paused complexes and a "slow" enzyme, in which the TL likely folds into an altered conformation, are resistant to Tgt. Our studies highlight the role of TL as a target through which accessory proteins and antibiotics can alter the elongation complex dynamics. PMID- 21976681 TI - Efnb1 and Efnb2 proteins regulate thymocyte development, peripheral T cell differentiation, and antiviral immune responses and are essential for interleukin 6 (IL-6) signaling. AB - Erythropoietin-producing hepatocellular kinases (Eph kinases) constitute the largest family of cell membrane receptor tyrosine kinases, and their ligand ephrins are also cell surface molecules. Because of promiscuous interaction between Ephs and ephrins, there is considerable redundancy in this system, reflecting the essential roles of these molecules in the biological system through evolution. In this study, both Efnb1 and Efnb2 were null-mutated in the T cell compartment of mice through loxP-mediated gene deletion. Mice with this double conditional mutation (double KO mice) showed reduced thymus and spleen size and cellularity. There was a significant decrease in the DN4, double positive, and single positive thymocyte subpopulations and mature CD4 and CD8 cells in the periphery. dKO thymocytes and peripheral T cells failed to compete with their WT counterparts in irradiated recipients, and the T cells showed compromised ability of homeostatic expansion. dKO naive T cells were inferior in differentiating into Th1 and Th17 effectors in vitro. The dKO mice showed diminished immune response against LCMV infection. Mechanistic studies revealed that IL-6 signaling in dKO T cells was compromised, in terms of abated induction of STAT3 phosphorylation upon IL-6 stimulation. This defect likely contributed to the observed in vitro and in vivo phenotype in dKO mice. This study revealed novel roles of Efnb1 and Efnb2 in T cell development and function. PMID- 21976683 TI - Multiple shifts between violet and ultraviolet vision in a family of passerine birds with associated changes in plumage coloration. AB - Colour vision in diurnal birds falls into two discrete classes, signified by the spectral sensitivity of the violet- (VS) or ultraviolet-sensitive (UVS) short wavelength-sensitive type 1 (SWS1) single cone. Shifts between sensitivity classes are rare; three or four are believed to have happened in the course of avian evolution, one forming UVS higher passerines. Such shifts probably affect the expression of shortwave-dominated plumage signals. We have used genomic DNA sequencing to determine VS or UVS affinity in fairy-wrens and allies, Maluridae, a large passerine family basal to the known UVS taxa. We have also spectrophotometrically analysed male plumage coloration as perceived by the VS and UVS vision systems. Contrary to any other investigated avian genus, Malurus (fairy-wrens) contains species with amino acid residues typical of either VS or UVS cone opsins. Three bowerbird species (Ptilonorhynchidae) sequenced for outgroup comparison carry VS opsin genes. Phylogenetic reconstructions render one UVS gain followed by one or more losses as the most plausible evolutionary scenario. The evolution of avian ultraviolet sensitivity is hence more complex, as a single shift no longer explains its distribution in Passeriformes. Character correlation analysis proposes that UVS vision is associated with shortwave reflecting plumage, which is widespread in Maluridae. PMID- 21976684 TI - Convenience polyandry or convenience polygyny? Costly sex under female control in a promiscuous primate. AB - Classic sex roles depict females as choosy, but polyandry is widespread. Empirical attempts to understand the evolution of polyandry have often focused on its adaptive value to females, whereas 'convenience polyandry' might simply decrease the costs of sexual harassment. We tested whether constraint-free female strategies favour promiscuity over mating selectivity through an original experimental design. We investigated variation in mating behaviour in response to a reversible alteration of sexual dimorphism in body mass in the grey mouse lemur, a small primate where female brief sexual receptivity allows quantifying polyandry. We manipulated body condition in captive females, predicting that convenience polyandry would increase when females are weaker than males, thus less likely to resist their solicitations. Our results rather support the alternative hypothesis of 'adaptive polyandry': females in better condition are more polyandrous. Furthermore, we reveal that multiple mating incurs significant energetic costs, which are strikingly symmetrical between the sexes. Our study shows that mouse lemur females exert tight control over mating and actively seek multiple mates. The benefits of remating are nevertheless not offset by its costs in low-condition females, suggesting that polyandry is a flexible strategy yielding moderate fitness benefits in this small mammal. PMID- 21976685 TI - A molecular palaeobiological hypothesis for the origin of aplacophoran molluscs and their derivation from chiton-like ancestors. AB - Aplacophorans have long been argued to be basal molluscs. We present a molecular phylogeny, including the aplacophorans Neomeniomorpha (Solenogastres) and Chaetodermomorpha (Caudofoveata), which recovered instead the clade Aculifera (Aplacophora + Polyplacophora). Our relaxed Bayesian molecular clock estimates an Early Ordovician appearance of the aculiferan crown group consistent with the presence of chiton-like molluscs with seven or eight dorsal shell plates by the Late Cambrian (approx. 501-490 Ma). Molecular, embryological and palaeontological data indicate that aplacophorans, as well as chitons, evolved from a paraphyletic assemblage of chiton-like ancestors. The recovery of cephalopods as a sister group to aculiferans suggests that the plesiomorphic condition in molluscs might be a morphology similar to that found in monoplacophorans. PMID- 21976686 TI - Climate change intensification of herbivore impacts on tree recruitment. AB - Altered species interactions are difficult to predict and yet may drive the response of ecological communities to climate change. We show that declining snowpack strengthens the impacts of a generalist herbivore, elk (Cervus elaphus), on a common tree species. Thick snowpack substantially reduces elk visitation to sites; aspen (Populus tremuloides) shoots in these areas experience lower browsing rates, higher survival and enhanced recruitment. Aspen inside herbivore exclosures have greatly increased recruitment, particularly at sites with thick snowpack. We suggest that long-term decreases in snowpack could help explain a widespread decline of aspen through previously unconsidered relationships. More generally, reduced snowpack across the Rocky Mountains, combined with rising elk populations, may remove the conditions needed for recruitment of this ecologically important tree species. These results highlight that herbivore behavioural responses to altered abiotic conditions are critical determinants of plant persistence. Predictions of climate change impacts must not overlook the crucial importance of species interactions. PMID- 21976688 TI - The genomic response to courtship song stimulation in female Drosophila melanogaster. AB - Courtship behaviour involves a complex exchange of signals and responses. These are usually studied at the phenotypic level, and genetic or transcriptional responses to courtship are still poorly understood. Here, we examine the gene expression changes in Drosophila melanogaster females in response to one of the key male courtship signals in mate recognition, song produced by male wing vibration. Using long oligonucleotide microarrays, we identified several genes that responded differentially to the presence or absence of acoustic courtship stimulus. These changes were modest in both the number of genes involved and fold changes, but notably dominated by antennal signalling genes involved in olfaction as well as neuropeptides and immune response genes. Second, we compared the expression patterns of females stimulated with synthetic song typical of either conspecific or heterospecific (Drosophila simulans) males. In this case, antennal olfactory signalling and innate immunity genes were also enriched among the differentially expressed genes. We confirmed and investigated the time course of expression differences of two identified immunity genes using real-time quantitative PCR. Our results provide novel insight into specific molecular changes in females in response to courtship song stimulation. These may be involved in both signal perception and interpretation and some may anticipate molecular interactions that occur between the sexes after mating. PMID- 21976687 TI - The causes of epistasis. AB - Since Bateson's discovery that genes can suppress the phenotypic effects of other genes, gene interactions-called epistasis-have been the topic of a vast research effort. Systems and developmental biologists study epistasis to understand the genotype-phenotype map, whereas evolutionary biologists recognize the fundamental importance of epistasis for evolution. Depending on its form, epistasis may lead to divergence and speciation, provide evolutionary benefits to sex and affect the robustness and evolvability of organisms. That epistasis can itself be shaped by evolution has only recently been realized. Here, we review the empirical pattern of epistasis, and some of the factors that may affect the form and extent of epistasis. Based on their divergent consequences, we distinguish between interactions with or without mean effect, and those affecting the magnitude of fitness effects or their sign. Empirical work has begun to quantify epistasis in multiple dimensions in the context of metabolic and fitness landscape models. We discuss possible proximate causes (such as protein function and metabolic networks) and ultimate factors (including mutation, recombination, and the importance of natural selection and genetic drift). We conclude that, in general, pleiotropy is an important prerequisite for epistasis, and that epistasis may evolve as an adaptive or intrinsic consequence of changes in genetic robustness and evolvability. PMID- 21976689 TI - Juvenile exposure to predator cues induces a larger egg size in fish. AB - When females anticipate a hazardous environment for their offspring, they can increase offspring survival by producing larger young. Early environmental experience determines egg size in different animal taxa. We predicted that a higher perceived predation risk by juveniles would cause an increase in the sizes of eggs that they produce as adults. To test this, we exposed juveniles of the mouthbrooding cichlid Eretmodus cyanostictus in a split-brood experiment either to cues of a natural predator or to a control situation. After maturation, females that had been confronted with predators produced heavier eggs, whereas clutch size itself was not affected by the treatment. This effect cannot be explained by a differential female body size because the predator treatment did not influence growth trajectories. The observed increase of egg mass is likely to be adaptive, as heavier eggs gave rise to larger young and in fish, juvenile predation risk drops sharply with increasing body size. This study provides the first evidence that predator cues perceived by females early in life positively affect egg mass, suggesting that these cues allow her to predict the predation risk for her offspring. PMID- 21976690 TI - Resistance to thermal stress in corals without changes in symbiont composition. AB - Discovering how corals can adjust their thermal sensitivity in the context of global climate change is important in understanding the long-term persistence of coral reefs. In this study, we showed that short-term preconditioning to higher temperatures, 3 degrees C below the experimentally determined bleaching threshold, for a period of 10 days provides thermal tolerance for the symbiosis stability between the scleractinian coral, Acropora millepora and Symbiodinium. Based on genotypic analysis, our results indicate that the acclimatization of this coral species to thermal stress does not come down to simple changes in Symbiodinium and/or the bacterial communities that associate with reef-building corals. This suggests that the physiological plasticity of the host and/or symbiotic components appears to play an important role in responding to ocean warming. The further study of host and symbiont physiology, both of Symbiodinium and prokaryotes, is of paramount importance in the context of global climate change, as mechanisms for rapid holobiont acclimatization will become increasingly important to the long-standing persistence of coral reefs. PMID- 21976691 TI - Experimental evidence that adult antipredator behaviour is heritable and not influenced by behavioural copying in a wild bird. AB - Knowledge of the relative importance of genetics and behavioural copying is crucial to appraise the evolvability of behavioural consistencies. Yet, genetic and non-genetic factors are often deeply intertwined, and experiments are required to address this issue. We investigated the sources of variation of adult antipredator behaviour in the Alpine swift (Apus melba) by making use of long term behavioural observations on parents and cross-fostered offspring. By applying an 'animal model' approach to observational data, we show that antipredator behaviour of adult Alpine swifts was significantly repeatable over lifetime (r = 0.273) and heritable (h(2) = 0.146). Regression models also show that antipredator behaviours differed between colonies and sexes (females were more tame), and varied with the hour and year of capture. By applying a parent offspring regression approach to 59 offspring that were exchanged as eggs or hatchlings between pairs of nests, we demonstrate that offspring behaved like their biological parents rather than like their foster parents when they were adults themselves. Those findings provide strong evidence that antipredator behaviour of adult Alpine swifts is shaped by genetics and/or pre-hatching maternal effects taking place at conception but not by behavioural copying. PMID- 21976692 TI - Population genomics of parallel phenotypic evolution in stickleback across stream lake ecological transitions. AB - Understanding the genetics of adaptation is a central focus in evolutionary biology. Here, we use a population genomics approach to examine striking parallel morphological divergences of parapatric stream-lake ecotypes of threespine stickleback fish in three watersheds on the Haida Gwaii archipelago, western Canada. Genome-wide variation at greater than 1000 single nucleotide polymorphism loci indicate separate origin of giant lake and small-bodied stream fish within each watershed (mean F(ST) between watersheds = 0.244 and within = 0.114). Genome scans within watersheds identified a total of 21 genomic regions that are highly differentiated between ecotypes and are probably subject to directional selection. Most outliers were watershed-specific, but genomic regions undergoing parallel genetic changes in multiple watersheds were also identified. Interestingly, several of the stream-lake outlier regions match those previously identified in marine-freshwater and benthic-limnetic genome scans, indicating reuse of the same genetic loci in different adaptive scenarios. We also identified multiple new outlier loci, which may contribute to unique aspects of differentiation in stream-lake environments. Overall, our data emphasize the important role of ecological boundaries in driving both local and broadly occurring parallel genetic changes during adaptation. PMID- 21976693 TI - Walkabout. PMID- 21976694 TI - Bad medicine: rheumatoid arthritis. PMID- 21976695 TI - An elected Libyan government should restore order to the health system. PMID- 21976696 TI - Infrastructure must replace focus on single diseases to speed up progress on health, says report. PMID- 21976697 TI - Development of an optimized backbone of FRET biosensors for kinases and GTPases. AB - Biosensors based on the principle of Forster (or fluorescence) resonance energy transfer (FRET) have shed new light on the spatiotemporal dynamics of signaling molecules. Among them, intramolecular FRET biosensors have been increasingly used due to their high sensitivity and user-friendliness. Time-consuming optimizations by trial and error, however, obstructed the development of intramolecular FRET biosensors. Here we report an optimized backbone for rapid development of highly sensitive intramolecular FRET biosensors. The key concept is to exclude the "orientation-dependent" FRET and to render the biosensors completely "distance dependent" with a long, flexible linker. We optimized a pair of fluorescent proteins for distance-dependent biosensors, and then developed a long, flexible linker ranging from 116 to 244 amino acids in length, which reduced the basal FRET signal and thereby increased the gain of the FRET biosensors. Computational simulations provided insight into the mechanisms by which this optimized system was the rational strategy for intramolecular FRET biosensors. With this backbone system, we improved previously reported FRET biosensors of PKA, ERK, JNK, EGFR/Abl, Ras, and Rac1. Furthermore, this backbone enabled us to develop novel FRET biosensors for several kinases of RSK, S6K, Akt, and PKC and to perform quantitative evaluation of kinase inhibitors in living cells. PMID- 21976698 TI - Arl13b regulates ciliogenesis and the dynamic localization of Shh signaling proteins. AB - Arl13b, a ciliary protein within the ADP-ribosylation factor family and Ras superfamily of GTPases, is required for ciliary structure but has poorly defined ciliary functions. In this paper, we further characterize the role of Arl13b in cilia by examining mutant cilia in vitro and determining the localization and dynamics of Arl13b within the cilium. Previously, we showed that mice lacking Arl13b have abnormal Sonic hedgehog (Shh) signaling; in this study, we show the dynamics of Shh signaling component localization to the cilium are disrupted in the absence of Arl13b. Significantly, we found Smoothened (Smo) is enriched in Arl13b-null cilia regardless of Shh pathway stimulation, indicating Arl13b regulates the ciliary entry of Smo. Furthermore, our analysis defines a role for Arl13b in regulating the distribution of Smo within the cilium. These results suggest that abnormal Shh signaling in Arl13b mutant embryos may result from defects in protein localization and distribution within the cilium. PMID- 21976699 TI - Role for a Cindr-Arf6 axis in patterning emerging epithelia. AB - Patterning of the Drosophila pupal eye is characterized by precise cell movements. In this paper, we demonstrate that these movements require an Arf regulatory cycle that connects surface receptors to actin-based movement. dArf6 activity-regulated by the Arf GTPase-activating proteins (ArfGAPs) dAsap and dArfGAP3 and the Arf GTP exchange factors Schizo and dPsd-promoted large cellular extensions; time-lapse microscopy indicated that these extensions presage cell rearrangements into correct epithelial niches. During this process, the Drosophila eye also requires interactions between surface Neph1/nephrin adhesion receptors Roughest and Hibris, which bind the adaptor protein Cindr (CD2AP). We provide evidence that Cindr forms a physical complex with dArfGAP3 and dAsap. Our data suggest this interaction sequesters ArfGAP function to liberate active dArf6 elsewhere in the cell. We propose that a Neph1/nephrin-Cindr/ArfGAP complex accumulates to limit local Arf6 activity and stabilize adherens junctions. Our model therefore links surface adhesion via an Arf6 regulatory cascade to dynamic modeling of the cytoskeleton, accounting for precise cell movements that organize the functional retinal field. Further, we demonstrate a similar relationship between the mammalian Cindr orthologue CD2AP and Arf6 activity in cell motility assays. We propose that this Cindr/CD2AP-mediated regulation of Arf6 is a widely used mechanism in emerging epithelia. PMID- 21976700 TI - Nse1-dependent recruitment of Smc5/6 to lesion-containing loci contributes to the repair defects of mutant complexes. AB - Of the three structural maintenance of chromosomes (SMC) complexes, Smc5/6 remains the most poorly understood. Genetic studies have shown that Smc5/6 mutants are defective in homologous recombination (HR), and consistent with this, Smc5/6 is enriched at lesions. However, Smc5/6 is essential for viability, but HR is not, and the terminal phenotype of null Smc5/6 mutants is mitotic failure. Here we analyze the function of Nse1, which contains a variant RING domain that is characteristic of ubiquitin ligases. Whereas deletion of this domain causes DNA damage sensitivity and mitotic failure, serine mutations in conserved cysteines do not. However, these mutations suppress the DNA damage sensitivity of Smc5/6 hypomorphs but not that of HR mutants and remarkably decrease the recruitment of Smc5/6 to loci containing lesions marked for HR-mediated repair. Analysis of DNA repair pathways in suppressed double mutants suggests that lesions are channeled into recombination-dependent and error-free postreplication repair. Thus the HR defect in Smc5/6 mutants appears to be due to the presence of dysfunctional complexes at lesions rather than to reflect an absolute requirement for Smc5/6 to complete HR. PMID- 21976701 TI - Protrudin serves as an adaptor molecule that connects KIF5 and its cargoes in vesicular transport during process formation. AB - Neurons are highly polarized cells with long neurites. Vesicular transport is required for neurite extension. We recently identified protrudin as a key regulator of vesicular transport during neurite extension. Expression of protrudin in nonneuronal cells thus induces formation of neurite-like membrane protrusions. We adopted a proteomics approach to identify proteins that associate with protrudin. Among the protrudin-associated proteins, including many with a function related to intracellular trafficking, we focused on KIF5, a motor protein that mediates anterograde vesicular transport in neurons. A coimmunoprecipitation assay confirmed that endogenous protrudin and KIF5 interact in mouse brain. Overexpression of KIF5 induced the formation of membrane protrusions in HeLa cells, reminiscent of the effect of protrudin overexpression. Forced expression of both protrudin and KIF5 promoted protrusion extension in a synergistic manner, whereas depletion of either protein attenuated protrusion formation. Protrudin facilitated the interaction of KIF5 with Rab11, VAP-A and B, Surf4, and RTN3, suggesting that protrudin serves as an adaptor protein and that the protrudin-KIF5 complex contributes to the transport of these proteins in neurons. Given that mutation of protrudin or KIF5 is a cause of human hereditary spastic paraplegia, the protrudin-KIF5 axis appears to be integral to neuronal function. PMID- 21976702 TI - Membrane fusion catalyzed by a Rab, SNAREs, and SNARE chaperones is accompanied by enhanced permeability to small molecules and by lysis. AB - The fusion of sealed biological membranes joins their enclosed aqueous compartments while mixing their membrane bilayers. Reconstituted fusion reactions are commonly assayed by lipid mixing, which can result from either true fusion or from lysis and its attendant reannealing of membranes. Fusion is also frequently assayed by the mixing of lumenal aqueous compartments, using probes of low molecular weight. With several probes (biotin, methylumbelliferyl-N-acetyl-alpha D-neuraminic acid, and dithionite), we find that yeast vacuolar SNAREs (SNAP [Soluble NSF attachment protein] Receptors) increase the permeability of membranes to small molecules and that this permeabilization is enhanced by homotypic fusion and vacuole protein sorting complex (HOPS) and Sec17p/Sec18p, the vacuolar tethering and SNARE chaperone proteins. We now report the development of a novel assay that allows the parallel assessment of lipid mixing, the mixing of intact lumenal compartments, any lysis that occurs, and the membrane permeation of small molecules. Applying this assay to an all-purified reconstituted system consisting of vacuolar lipids, the four vacuolar SNAREs, the SNARE disassembly chaperones Sec17p and Sec18p, the Rab Ypt7p, and the Rab effector/SM protein complex HOPS, we show that true fusion is accompanied by strongly enhanced membrane permeability to small molecules and a measurable rate of lysis. PMID- 21976704 TI - Managing perioperative risk in patients undergoing elective non-cardiac surgery. PMID- 21976703 TI - Deficiencies in lamin B1 and lamin B2 cause neurodevelopmental defects and distinct nuclear shape abnormalities in neurons. AB - Neuronal migration is essential for the development of the mammalian brain. Here, we document severe defects in neuronal migration and reduced numbers of neurons in lamin B1-deficient mice. Lamin B1 deficiency resulted in striking abnormalities in the nuclear shape of cortical neurons; many neurons contained a solitary nuclear bleb and exhibited an asymmetric distribution of lamin B2. In contrast, lamin B2 deficiency led to increased numbers of neurons with elongated nuclei. We used conditional alleles for Lmnb1 and Lmnb2 to create forebrain specific knockout mice. The forebrain-specific Lmnb1- and Lmnb2-knockout models had a small forebrain with disorganized layering of neurons and nuclear shape abnormalities, similar to abnormalities identified in the conventional knockout mice. A more severe phenotype, complete atrophy of the cortex, was observed in forebrain-specific Lmnb1/Lmnb2 double-knockout mice. This study demonstrates that both lamin B1 and lamin B2 are essential for brain development, with lamin B1 being required for the integrity of the nuclear lamina, and lamin B2 being important for resistance to nuclear elongation in neurons. PMID- 21976705 TI - TGFbeta-activated kinase 1 (TAK1)-binding proteins (TAB) 2 and 3 negatively regulate autophagy. AB - Transforming growth factor beta-activated protein kinase 1 (TAK1)-binding protein 2 (TAB2) and its close homolog TAB3 are initially characterized as adapter proteins essential for TAK1 activation in response to interleukin-1beta and tumour necrosis factor-alpha. However, the physiological roles of TAB2 and TAB3 are still not fully understood. Here we report that TAB2 and TAB3 bind to Beclin1 and colocalize in the cytoplasm. TAB2 also interacts with ATG13 and is phosphorylated by ULK1. Overexpression of TAB2 or TAB3 induces punctate localization of ATG5 under the normal culture condition. Knockdown of TAB2 and TAB3 results in the decrease in endogenous protein level of p62/SQSTM1 under the normal culture condition, while overexpression of TAB2 results in the accumulation of p62/SQSTM1 independently of TAK1. The decrease of p62/SQSTM1 induced by the knockdown of TAB2 and TAB3 is largely dependent on ATG5. These results suggest that TAB2 and TAB3 negatively regulate autophagy independently of TAK1 activity. PMID- 21976706 TI - Inhibitory effect of sulphated polysaccharide porphyran on nitric oxide production in lipopolysaccharide-stimulated RAW264.7 macrophages. AB - Porphyran, extracted from an edible red alga (Porphyra yezoensis), is a sulphated polysaccharide with a wide variety of biological activities including anti tumour, antioxidant and immuno-modulating activities. In this study, we examined the effect of porphyran on nitric oxide (NO) production in mouse macrophage cell line RAW264.7 cells. Although no significant activity of porphyran to induce NO or tumour necrosis factor-alpha (TNF-alpha) production in RAW264.7 cells was observed at the concentration range tested (10-500 ug/ml), it was found for the first time that porphyran inhibited NO production and expression of inducible nitric oxide synthase (iNOS) in RAW264.7 cells stimulated with lipopolysaccharide (LPS). In the presence of 500 ug/ml porphyran, NO production and expression of iNOS in LPS-treated RAW264.7 cells were completely suppressed. On the other hand, porphyran showed only a marginal effect on the secretion of TNF-alpha from LPS stimulated RAW264.7 cells. Electrophoretic mobility shift assay (EMSA) using infrared dye labelled oligonucleotide with nuclear factor-kappaB (NF-kappaB) consensus sequence suggested that porphyran inhibited the LPS-induced NF-kappaB activation. The LPS-inducible nuclear translocation of p65, and the phosphorylation and degradation of IkappaB-alpha were also inhibited by the pre treatment with porphyran. Our results obtained in in vitro analysis suggest that porphyran suppresses NO production in LPS-stimulated macrophages by the blocking of NF-kappaB activation. PMID- 21976707 TI - The binding site of bisphenol A to protein disulphide isomerase. AB - Protein disulphide isomerase (PDI) has been isolated as a binding protein of bisphenol A (BPA) in the rat brain. In this study, we determined binding sites of BPA to PDI and characterized the binding site. First, we identified the BPA binding domain with ab, b'a'c, a, b, b' and a'c fragment peptides of PDI by surface plasmon resonance spectroscopy. BPA interacted with ab, b'a 'c, a and b', suggesting that a and b' domains are important in their interaction. Second, ab, b'a'c, a,b,b',a', abb'a', abb', b'a', Deltab' and a'c fragment peptides were used for their isomerase activity with RNase as a substrate. BPA could inhibit the activity of peptide fragments including b', suggesting that b' domain contributes to inhibition of catalytic activity of PDI by BPA. Next, we investigated the BPA binding capacity of PDI by amino acid substitution. PDI lost the BPA-binding activity by the mutation of H258 and mutation of Q245 and N300 also decreased its activity. Furthermore, acidic condition increased the BPA-binding activity of PDI. These results suggest that the charge of these amino acid especially, H258, is important for the BPA to bind to PDI. PMID- 21976708 TI - Ectodomain shedding of HB-EGF: a potential target for cancer therapy. AB - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is synthesized as a membrane-anchored protein, known as proHB-EGF. ProHB-EGF is cleaved by metalloproteases through a process referred to as 'ectodomain shedding', resulting in the formation of soluble HB-EGF. Both proHB-EGF and soluble HB-EGF are biologically active; the former acts on neighbouring cells through juxtacrine signalling, whereas the latter can move to distant locations. Elevated HB-EGF expression has been observed in ovarian and some other cancers. CRM197, a diphtheria toxin (DT) mutant, binds directly to the epidermal growth factor (EGF)-like domain and represses the mitogenic activity of HB-EGF. Recently, monoclonal antibodies (mAbs) specific for human HB-EGF were generated by immunizing HB-EGF-deficient mice with human HB-EGF (Hamaoka et al. (2010) J. Biochem. 148, 55-69). Most of the mAbs can bind to the EGF-like domain of HB-EGF, but fail to inhibit the mitogenic activity of soluble HB-EGF. However, some mAbs prevented the ectodomain shedding of proHB-EGF and inhibited the proliferation of EGF receptor-expressing cells stimulated by proHB-EGF-expressing cells. Hamaoka et al. showed that CRM197 prevents the ectodomain shedding of proHB-EGF. Thus, these mAbs function as specific inhibitors for the ectodomain shedding of HB-EGF and may be useful for treating cancers exhibiting elevated levels of HB-EGF. PMID- 21976709 TI - DRD2 genotype-based variation of default mode network activity and of its relationship with striatal DAT binding. AB - The default mode network (DMN) comprises a set of brain regions with "increased" activity during rest relative to cognitive processing. Activity in the DMN is associated with functional connections with the striatum and dopamine (DA) levels in this brain region. A functional single-nucleotide polymorphism within the dopamine D2 receptor gene (DRD2, rs1076560 G > T) shifts splicing of the 2 D2 isoforms, D2 short and D2 long, and has been associated with striatal DA signaling as well as with cognitive processing. However, the effects of this polymorphism on DMN have not been explored. The aim of this study was to evaluate the effects of rs1076560 on DMN and striatal connectivity and on their relationship with striatal DA signaling. Twenty-eight subjects genotyped for rs1076560 underwent functional magnetic resonance imaging during a working memory task and 123 55 I-Fluoropropyl-2-beta-carbomethoxy-3-beta(4-iodophenyl) nortropan Single Photon Emission Computed Tomography ([(123)I]-FP-CIT SPECT) imaging (a measure of dopamine transporter [DAT] binding). Spatial group-independent component (IC) analysis was used to identify DMN and striatal ICs. Within the anterior DMN IC, GG subjects had relatively greater connectivity in medial prefrontal cortex (MPFC), which was directly correlated with striatal DAT binding. Within the posterior DMN IC, GG subjects had reduced connectivity in posterior cingulate relative to T carriers. Additionally, rs1076560 genotype predicted connectivity differences within a striatal network, and these changes were correlated with connectivity in MPFC and posterior cingulate within the DMN. These results suggest that genetically determined D2 receptor signaling is associated with DMN connectivity and that these changes are correlated with striatal function and presynaptic DA signaling. PMID- 21976710 TI - Social cognitive impairments and negative symptoms in schizophrenia: are there subtypes with distinct functional correlates? AB - Social cognitive impairments and negative symptoms are core features of schizophrenia closely associated with impaired community functioning. However, little is known about whether these are independent dimensions of illness and if so, whether individuals with schizophrenia can be meaningfully classified based on these dimensions (SANS) and potentially differentially treated. Five social cognitive measures plus Scale for the Assessment of Negative Symptoms (SANS) and Positive and Negative Syndrome Scale (PANSS) scores in a sample of 77 outpatients produced 2 distinct factors--a social cognitive factor and a negative symptom factor. Factor scores were used in a cluster analysis, which yielded 3 well defined groupings--a high negative symptom group (HN) and 2 low negative symptom groups, 1 with higher social cognition (HSC) and 1 with low social cognition (LSC). To make these findings more practicable for research and clinical settings, a rule of thumb for categorizing using only the Mayer-Salovey-Caruso Emotional Intelligence Test and PANSS negative component was created and produced 84.4% agreement with the original cluster groups. An additional 63 subjects were added to cross validate the rule of thumb. When samples were combined (N = 140), the HSC group had significantly better quality of life and Global Assessment of Functioning (GAF) scores, higher rates of marriage and more hospitalizations. The LSC group had worse criminal and substance abuse histories. With 2 common assessment instruments, people with schizophrenia can be classified into 3 subgroups that have different barriers to community integration and could potentially benefit from different treatments. PMID- 21976711 TI - De Novo assembly of the Manila clam Ruditapes philippinarum transcriptome provides new insights into expression bias, mitochondrial doubly uniparental inheritance and sex determination. AB - Males and females share the same genome, thus, phenotypic divergence requires differential gene expression and sex-specific regulation. Accordingly, the analysis of expression patterns is pivotal to the understanding of sex determination mechanisms. Many bivalves are stable gonochoric species, but the mechanism of gonad sexualization and the genes involved are still unknown. Moreover, during the period of sexual rest, a gonad is not present and sex cannot be determined. A mechanism associated with germ line differentiation in some bivalves, including the Manila clam Ruditapes philippinarum, is the doubly uniparental inheritance (DUI) of mitochondria, a variation of strict maternal inheritance. Two mitochondrial lineages are present, one transmitted through eggs and the other through sperm, as well as a mother-dependent sex bias of the progeny. We produced a de novo annotation of 17,186 transcripts from R. philippinarum and compared the transcriptomes of males and females and identified 1,575 genes with strong sex-specific expression and 166 sex-specific single nucleotide polymorphisms, obtaining preliminary information about genes that could be involved in sex determination. Then we compared the transcriptomes between a family producing predominantly females and a family producing predominantly males to identify candidate genes involved in regulation of sex specific aspects of DUI system, finding a relationship between sex bias and differential expression of several ubiquitination genes. In mammalian embryos, sperm mitochondria are degraded by ubiquitination. A modification of this mechanism is hypothesized to be responsible for the retention of sperm mitochondria in male embryos of DUI species. Ubiquitination can additionally regulate gene expression, playing a role in sex determination of several animals. These data enable us to develop a model that incorporates both the DUI literature and our new findings. PMID- 21976713 TI - OsGLU3, a putative membrane-bound endo-1,4-beta-glucanase, is required for root cell elongation and division in rice (Oryza sativa L.). AB - Plant roots move through the soil by elongation. This is vital to their ability to anchor the plant and acquire water and minerals from the soil. In order to identify new genes involved in root elongation in rice, we screened an ethyl methane sulfonate (EMS)-mutagenized rice library, and isolated a short root mutant, Osglu3-1. The map-based cloning results showed that the mutant was due to a point mutation in OsGLU3, which encodes a putative membrane-bound endo-1,4-beta glucanase. Osglu3-1 displayed less crystalline cellulose content in its root cell wall, shorter root cell length, and a slightly smaller root meristem as visualized by restricted expression of OsCYCB1,1:GUS. Exogenous application of glucose can suppress both the lower root cell wall cellulose content and short root phenotypes of Osglu3-1. Consistently, OsGLU3 is ubiquitously expressed in various tissues with strong expression in root tip, lateral root, and crown root primodia. The fully functional OsGLU3-GFP was detected in plasma membrane, and FM4-64-labeled compartments in the root meristem and elongation zones. We also found that phosphate starvation, an environmental stress, altered cell wall cellulose content to modulate root elongation in a OsGLU3-dependant way. PMID- 21976712 TI - IL-6 promotes head and neck tumor metastasis by inducing epithelial-mesenchymal transition via the JAK-STAT3-SNAIL signaling pathway. AB - Epithelial-mesenchymal transition (EMT) is a key process in tumor metastatic cascade that is characterized by the loss of cell-cell junctions and cell polarity, resulting in the acquisition of migratory and invasive properties. However, the precise molecular events that initiate this complex EMT process in head and neck cancers are poorly understood. Increasing evidence suggests that tumor microenvironment plays an important role in promoting EMT in tumor cells. We have previously shown that head and neck tumors exhibit significantly higher Bcl-2 expression in tumor-associated endothelial cells and overexpression of Bcl 2 alone in tumor-associated endothelial cells was sufficient to enhance tumor metastasis of oral squamous cell carcinoma in a severe combined immunodeficient (SCID) mouse model. In this study, we show that endothelial cells expressing Bcl 2 (EC-Bcl-2), when cocultured with head and neck tumor cells (CAL27), significantly enhance EMT-related changes in tumor cells predominantly by the secretion of IL-6. Treatment with recombinant IL-6 or stable IL-6 overexpression in CAL27 cells or immortalized oral epithelial cells (IOE) significantly induced the expression of mesenchymal marker, vimentin, while repressing E-cadherin expression via the JAK/STAT3/Snail signaling pathway. These EMT-related changes were further associated with enhanced tumor and IOE cell scattering and motility. STAT3 knockdown significantly reversed IL-6-mediated tumor and IOE cell motility by inhibiting FAK activation. Furthermore, tumor cells overexpressing IL-6 showed marked increase in lymph node and lung metastasis in a SCID mouse xenograft model. Taken together, these results show a novel function for IL-6 in mediating EMT in head and neck tumor cells and increasing their metastatic potential. PMID- 21976714 TI - Nuclear targeting of methyl-recycling enzymes in Arabidopsis thaliana is mediated by specific protein interactions. AB - Numerous transmethylation reactions are required for normal plant growth and development. S-adenosylhomocysteine hydrolase (SAHH) and adenosine kinase (ADK) act coordinately to recycle the by-product of these reactions, S adenosylhomocysteine (SAH) that would otherwise competitively inhibit methyltransferase (MT) activities. Here, we report on investigations to understand how the SAH produced in the nucleus is metabolized by SAHH and ADK. Localization analyses using green fluorescent fusion proteins demonstrated that both enzymes are capable of localizing to the cytoplasm and the nucleus, although no obvious nuclear localization signal was found in their sequences. Deletion analysis revealed that a 41-amino-acid segment of SAHH (Gly(150)-Lys(190)) is required for nuclear targeting of this enzyme. This segment is surface exposed, shows unique sequence conservation patterns in plant SAHHs, and possesses additional features of protein-protein interaction motifs. ADK and SAHH interact in Arabidopsis via this segment and also interact with an mRNA cap MT. We propose that the targeting of this complex is directed by the nuclear localization signal of the MT; other MTs may similarly target SAHH/ADK to other subcellular compartments to ensure uninterrupted transmethylation. PMID- 21976715 TI - MicroRNA expression profiles distinguish the carcinogenic effects of riddelliine in rat liver. AB - Pyrrolizidine alkaloids (PAs) are the most common plant constituents that poison livestock, wildlife and humans. Riddelliine is a prototype genotoxic PA and has been nominated to be classified as a reasonably anticipated human carcinogen by the US National Toxicology Program (NTP) in the 12th Report on Carcinogens. Riddelliine's nomination is due to the high incidence of liver tumours that were observed in both mice and rats in the NTP tumourigenicity bioassay study. In this current study, we explored whether riddelliine treatment could alter microRNA (miRNA) expression in rat liver and whether the possible deregulation of miRNA was related to mutagenicity and carcinogenicity of riddelliine. Groups of six rats were administered riddelliine at a mutagenic dose of 1 mg/kg body weight or with control vehicle 5 days a week for 12 weeks. A group of six rats treated with aristolochic acid, a renal carcinogen, was used as a tissue-specific negative control. The animals were sacrificed 1 day after the last treatment and the livers were isolated for miRNA expression analysis using miRNA microarrays. miRNA expression was significantly altered by riddelliine treatment. Principal component analysis and hierarchical clustering analysis showed that the miRNA expression profiles were clearly classified into two groups, riddelliine treatment versus other samples. Forty-seven miRNAs were significantly dysregulated by riddelliine treatment, among which 38 were up-regulated and 9 were down-regulated. Functional analysis of these differentially expressed miRNAs by riddelliine revealed that these miRNAs were involved in liver carcinogenicity and toxicity, such as liver proliferation, liver necrosis/cell death, hepatocellular carcinoma, liver hepatomegaly, liver inflammation and liver fibrosis. These results suggest that miRNAs actively respond to a mutagenic dose of riddelliine and the pattern of miRNA expression has the potential to be used as a biomarker of genotoxicity and carcinogenicity for riddelliine and possibly other PAs. PMID- 21976716 TI - p73 G4C14-to-A4T14 gene polymorphism and interaction with p53 exon 4 Arg72Pro on cancer susceptibility: a meta-analysis of the literature. AB - The p73 gene (1p36-33) is involved in cancer development through cell growth inhibition by inducing apoptosis in a p53-like manner. The p73 G4C14-to-A4T14 dinucleotide polymorphism, consisting of two single-nucleotide polymorphisms in the non-coding region of exon 2 that are in complete linkage disequilibrium, has been extensively studied in association with cancer risk. We performed a meta analysis of published studies that examined the association between this p73 G4C14-to-A4T14 polymorphism and cancer by searching for relevant studies on Medline and Embase up to February 28, 2010. Pooling data from 19 case-control studies that included 6510 cancer cases and 5711 controls, we found that carriers of the p73 G4C14-to-A4T14 homozygous variant genotype (AT/AT) had an increased global risk of cancer [odds ratio (OR) = 1.30, 95% confidence interval (CI), 1.03 1.65]. There was no evidence of an effect modification of p73 AT/AT by age, gender, ethnicity or smoking status in subgroup analyses; however, a 1.35-fold statistically significant increased risk was found among individuals <55 years old. In case-only analysis, the homozygous p73 G4C14-to-A4T14 variant of p73 genotype was associated with the presence of the p53 exon 4 Arg72Pro allele (OR = 1.30, 95% CI, 1.02-1.64), which is suggestive of a biological interaction between the two genes in carcinogenesis. In conclusion, the p73 G4C14-to-A4T14 homozygous variant genotype might be a risk factor for cancer, especially in combination with the p53 exon 4 Arg72Pro polymorphism. Further studies looking at p73 G4C14 to-A4T14 and p53 exon 4 Arg72Pro interaction are required to support our findings. PMID- 21976717 TI - Smad2: a candidate gene for the murine autoimmune diabetes locus Idd21.1. AB - CONTEXT: Congenic NOD.ABH(D18Mit8-D18Mit214) mice, which contain greater than 12.8 Mb of DNA encompassing Idd21.1 from diabetes-resistant Biozzi/ABH mice, have a lower frequency of diabetes compared with the parental nonobese diabetic (NOD) strain, possibly due to reduced pathogenicity of beta-islet-infiltrating immune cells. OBJECTIVE: The objective of the study was to identify an Idd21.1 candidate gene. METHODS: The methods used in the study were adoptive transfer into scid mice lacking an adaptive immune system; dendritic cell phenotyping and gene expression analysis; and fine-mapping Idd21.1 by congenic mapping. RESULTS: Diabetes incidences of NOD.scid.ABH(D18Mit8-D18Mit214) mice receiving splenocytes from NOD and NOD.ABH(D18Mit8-D18Mit214) were similar to that previously observed in NOD.scid recipients, suggesting that the diabetes resistance in NOD.ABH(D18Mit8-D18Mit214) is primarily mediated by the adaptive immune system, findings supported by adoptive transfer of CD4(+) T cells. In activated dendritic cells, there were no conclusive differences in cytokine profiles and activation marker expression. However, microarray analysis comparing gene expression between activated dendritic cells from NOD and NOD.ABH (D18Mit8-D18Mit214) revealed that Smad2, in a maximal 6.5-Mb region to which Idd21.1 was further resolved by congenic mapping, was differentially expressed (increased in NOD). Quantitative real-time PCR confirmed the differential expression of Smad2, and other genes in the TGF-beta signaling pathway, in activated dendritic cells. CONCLUSIONS: These results implicate Smad2 as an Idd21.1 candidate and Smad2 and the TGF-beta signaling pathway in activated dendritic cells in diabetogenesis. With suggestive evidence from human genome-wide association studies supporting a role for SMAD7 in human type 1 diabetes, a comprehensive genetic investigation of the SMAD genes in type 1 diabetes is warranted. PMID- 21976718 TI - Higher testosterone levels are associated with less loss of lean body mass in older men. AB - CONTEXT: Little information exists about longitudinal changes in body composition and physical function in relation to sex hormone levels in older men. OBJECTIVE: The aim of the study was to determine associations of testosterone, estradiol, and SHBG with changes in body composition and physical function. DESIGN AND SETTING: We conducted a prospective cohort study within the Osteoporotic Fractures in Men (MrOS) study at six U.S. clinical centers. PARTICIPANTS: A total of 5994 ambulatory men aged 65 yr or older enrolled in the MrOS. We examined 1183 men with complete measures of sex steroid hormones, body composition, and some measure of physical function. INTERVENTION: There were no interventions. MAIN OUTCOME MEASURE(S): Sex steroids were measured by mass spectrometry in serum collected at baseline. Measurements of body composition using dual-energy x-ray absorptiometry and physical performance (grip strength, leg power, timed chair stands, narrow walk, and 6-m walk) were performed at baseline and repeated 4.5 yr later. RESULTS: Overall, men lost 1.3 kg (+/-4.4 sd) weight between study visits. Lean mass, especially appendicular, declined less at higher baseline testosterone levels (P < 0.05). These associations were most evident in the 40% of men who lost more than 2.0 kg during follow-up. In weight losers, higher testosterone was associated with less decline in timed chair stands. Estradiol was not related to body composition or physical function changes. Higher SHBG was associated with less loss of appendicular lean mass and grip strength. CONCLUSIONS: Higher endogenous testosterone is associated with reduced loss of lean mass and lower extremity function in older men losing weight. Endogenous testosterone may contribute to healthy aging. PMID- 21976719 TI - Hypercalciuria associated with high dietary protein intake is not due to acid load. AB - CONTEXT AND OBJECTIVE: Dietary intake of animal proteins is associated with an increase in urinary calcium and nephrolithiasis risk. We tested the hypothesis that the acid load imposed by dietary proteins causes this hypercalciuria. DESIGN AND SETTING: In a short-term crossover metabolic study, an alkali salt was provided with a high-protein diet (HPD) to neutralize the acid load imparted by dietary proteins. PARTICIPANTS AND INTERVENTIONS: Eleven healthy volunteers were evaluated at the end of each of four phases while consuming metabolic diets with fixed calcium and sodium content. Phases 1 and 3 consisted of a control diet (CD). Phases 2 and 4 consisted of a eucaloric HPD (60 g/d animal proteins added to CD). Along with HPD in phases 2 and 4, subjects ingested 30 mEq twice daily of either potassium citrate (KCitrate, alkaline salt) or potassium chloride (KCl, control neutral salt). RESULTS: KCitrate completely neutralized the acid load imparted by HPD (based on changes in urine pH and net acid excretion) and increased urinary citrate. Urinary calcium increased during both HPD phases compared with CD but was not significantly different between the HPD + KCl and HPD + KCitrate phases (182 +/- 85 vs. 170 +/- 85 mg/d; P = 0.28). Increased urinary saturation with respect to calcium oxalate and uric acid with HPD was abrogated by KCitrate. CONCLUSIONS: This study suggests that, at least in the short-term, mechanism(s) other than acid load account for hypercalciuria induced by HPD. The beneficial effect of KCitrate on nephrolithiasis risk with HPD is through correction of declines in urine pH and citrate. PMID- 21976720 TI - PAX8 mutation disturbing thyroid follicular growth: a case report. AB - CONTEXT: Heterozygous inactivating PAX8 mutations cause congenital hypothyroidism. Although more than 30 mutation carriers have been reported, no histological examination of the thyroid has been conducted. OBJECTIVE: The objective of this study was to document the histological characteristics of the thyroid tissue harboring a PAX8 mutation. SUBJECTS AND METHODS: The patient was a 40-yr-old female, whose two children had congenital hypothyroidism and an inactivating PAX8 mutation (p.K80_A84dup). She had normal thyroid function but had a thyroid nodule and received right hemithyroidectomy at age 28 yr. Mutation analyses using DNA derived from multiple sources, namely lymphocytes, nails, and laser capture microdissected thyroid samples, were performed. RESULTS: The PAX8 mutation was detected in the lymphocytes; however, the level of the mutant allele was significantly lower than that of the wild-type allele. This finding was compatible with her somatic mosaic state. We reviewed the histology of her resected thyroid and found a characteristic lesion in the nonneoplastic tissue: dense aggregates of thyrocytes with absent or very small follicles, resembling a fetal thyroid in the late phase of development. Mutation analyses of laser capture microdissected thyroid samples revealed that the fetal-like tissue carried the PAX8 mutation, whereas surrounding morphologically normal tissue and adenoma tissue did not. CONCLUSIONS: In our case, the histology of PAX8 mutation carrying thyroid tissue was characterized by the lack of follicular growth. Our observations provide the first evidence suggesting that the late phase of thyroid development is sensitive to the PAX8 gene dosage and can be disturbed by heterozygous inactivating PAX8 mutations. PMID- 21976721 TI - The MC4R(I251L) allele is associated with better metabolic status and more weight loss after gastric bypass surgery. AB - CONTEXT: Factors that influence long-term weight loss after Roux-en Y gastric bypass (RYGB) surgeries are poorly defined. The melanocortin system plays an important role in regulating energy homeostasis, satiety, and glucose metabolism. Variations of the MC4R comprise the most prevalent monogenetic obesity disorder. OBJECTIVE: The objective of the study was to examine the role of MC4R variants and diabetic status in long-term weight loss after RYGB. PARTICIPANTS AND METHODS: In 1433 extremely obese patients who underwent RYGB, we sequenced for genetic variants of MC4R. We examined the MC4R genotype and its relationship with weight loss profile, and clinical phenotypes accumulated during a 48-month period before and after surgery. RESULTS: We found 80 subjects with rare and common variants of MC4R in the RYGB cohort. Among these, 26 and 36 patients carry the I251L and V103I variants, respectively. These common alleles are negatively associated with obesity. Remarkably, after the 12-month presurgery caloric restriction and RYGB, I251L allele carriers lost 9% more weight (~9 kg) compared with the noncarriers, continued rapid weight loss longer, regained less weight, and had lower presurgery homeostatic model assessment for insulin resistance values. Normoglycemic, I251L allele carriers lost more weight compared with their diabetic and prediabetic counterparts and maintained their weight loss. Among noncarriers, normoglycemic individuals initially lost more weight compared with dysglycemics, but this difference was not maintained in the long term. CONCLUSIONS: Individuals carrying the I251L common allele are predisposed to better clinical outcome, reduced risk of type 2 diabetes, and better weight loss during diet and surgical interventions. Diabetic status has only a small, short term effect on weight loss after RYGB. PMID- 21976722 TI - Hereditary pituitary hyperplasia with infantile gigantism. AB - CONTEXT: We report hereditary pituitary hyperplasia. OBJECTIVE: The objective of the study was to describe the results of the clinical and laboratory analysis of this rare instance of hereditary pituitary hyperplasia. DESIGN: The study is a retrospective analysis of three cases from one family. SETTING: The study was conducted at the National Institutes of Health, a tertiary referral center. PATIENTS: A mother and both her sons had very early-onset gigantism associated with high levels of serum GH and prolactin. INTERVENTIONS: The condition was treated by total hypophysectomy. MAIN OUTCOME MEASURE(S): We performed clinical, pathological, and molecular evaluations, including evaluation basal and provocative endocrine testing, neuroradiological assessment, and assessment of the pituitary tissue by microscopic evaluation, immunohistochemistry, and electron microscopy. RESULTS: All three family members had very early onset of gigantism associated with abnormally high serum levels of GH and prolactin. Serum GHRH levels were not elevated in either of the boys. The clinical, radiographic, surgical, and histological findings indicated mammosomatotroph hyperplasia. The pituitary gland of both boys revealed diffuse mammosomatotroph hyperplasia of the entire pituitary gland without evidence of adenoma. Prolactin and GH were secreted by the same cells within the same secretory granules. Western blot and immunohistochemistry demonstrated expression of GHRH in clusters of cells distributed throughout the hyperplastic pituitary of both boys. CONCLUSIONS: This hereditary condition seems to be a result of embryonic pituitary maldevelopment with retention and expansion of the mammosomatotrophs. The findings suggest that it is caused by paracrine or autocrine pituitary GHRH secretion during pituitary development. PMID- 21976723 TI - Adjuvant radioactive therapy after reoperation for locoregionally recurrent papillary thyroid cancer in patients who initially underwent total thyroidectomy and high-dose remnant ablation. AB - CONTEXT: Some patients have elevated stimulated thyroglobulin (sTg) concentrations after reoperation for locoregionally recurrent/persistent papillary thyroid cancer (PTC). Little is known, however, about the efficacy of adjuvant radioactive iodine (RAI) therapy in these patients. OBJECTIVE: The objective of the study was to evaluate the efficacy of adjuvant RAI therapy in patients with elevated sTg after reoperation for locally recurrent/persistent PTC. DESIGN AND SETTINGS: This was a retrospective observational cohort study in a tertiary referral hospital. PATIENTS: We evaluated 45 consecutive patients with sTg greater than 2 ng/ml after reoperation for locoregionally recurrent PTC, all of whom had previously undergone initial total thyroidectomy followed by high dose RAI remnant ablation. Of these 45 patients, 23 received adjuvant RAI therapy (adjuvant group) and 22 did not (control group). MAIN OUTCOME MEASURES: Main outcome measures included changes in sTg concentration after reoperation and disease-free survival. RESULTS: Over time, there were no significant differences in mean sTg concentration in the adjuvant (P = 0.35) and control (P = 0.74) groups. Only 15% of patients in the adjuvant group and 33% in the control group showed a greater than 50% decrease in sTg level from baseline. There were no between-group differences in changes (P = 0.83) or percent decrease (P = 0.97) in sTg concentration and no difference in clinical recurrence-free survival (P = 0.20). CONCLUSION: In patients who still have elevated sTg after reoperation for locally recurrent/persistent PTC, adjuvant RAI therapy compared with no additional RAI therapy resulted in no significant differences in the subsequent sTg changes or the recurrence-free survival. PMID- 21976724 TI - The effects of kisspeptin-10 on reproductive hormone release show sexual dimorphism in humans. AB - BACKGROUND: Kisspeptin peptides are critical in human reproductive physiology and are potential therapies for infertility. Kisspeptin-10 stimulates gonadotropin release in both male and female rodents. However, few studies have investigated the effects of kisspeptin-10 on gonadotropin release in humans, and none have investigated the effect in women. If kisspeptin is to be useful for treating reproductive disease, its effects in both men and women must be established. AIM: To compare the effects of kisspeptin-10 administration on reproductive hormone release in healthy men and women. METHODS: Intravenous bolus kisspeptin-10 was administered to men and women (n = 4-5 per group). Subcutaneous bolus and i.v. infusion of kisspeptin-10 was also administered to female women (n = 4-5 per group). Circulating reproductive hormones were measured. RESULTS: In healthy men, serum LH and FSH were elevated after i.v. bolus kisspeptin-10, at doses as low as 0.3 and 1.0 nmol/kg, respectively. In healthy women during the follicular phase of the menstrual cycle, no alterations in serum gonadotropins were observed after i.v. bolus, s.c. bolus, or i.v. infusion of kisspeptin-10 at maximal doses of 10 nmol/kg, 32 nmol/kg, and 720 pmol/kg/min, respectively. In women during the preovulatory phase, serum LH and FSH were elevated after i.v. bolus kisspeptin-10 (10 nmol/kg). CONCLUSION: Kisspeptin-10 stimulates gonadotropin release in men as well as women during the preovulatory phase of menstrual cycle but fails to stimulate gonadotropin release in women during the follicular phase. The sexual dimorphism of the responsiveness of healthy men and women to kisspeptin-10 administration has important clinical implications for the potential of kisspeptin-10 to treat disorders of reproduction. PMID- 21976725 TI - Coexisting/Coexpressing Genomic Libraries (CoGeL) identify interactions among distantly located genetic loci for developing complex microbial phenotypes. AB - In engineering novel microbial strains for biotechnological applications, beyond a priori identifiable pathways to be engineered, it is becoming increasingly important to develop complex, ill-defined cellular phenotypes. One approach is to screen genomic or metagenomic libraries to identify genes imparting desirable phenotypes, such as tolerance to stressors or novel catabolic programs. Such libraries are limited by their inability to identify interactions among distant genetic loci. To solve this problem, we constructed plasmid- and fosmid-based Escherichia coli Coexisting/Coexpressing Genomic Libraries (CoGeLs). As a proof of principle, four sets of two genes of the l-lysine biosynthesis pathway distantly located on the E. coli chromosome were knocked out. Upon transformation of these auxotrophs with CoGeLs, cells growing without supplementation were found to harbor library inserts containing the knocked-out genes demonstrating the interaction between the two libraries. CoGeLs were also screened to identify genetic loci that work synergistically to create the considerably more complex acid-tolerance phenotype. CoGeL screening identified combination of genes known to enhance acid tolerance (gadBC operon and adiC), but also identified the novel combination of arcZ and recA that greatly enhanced acid tolerance by 9000-fold. arcZ is a small RNA that we show increases pH tolerance alone and together with recA. PMID- 21976726 TI - Prioritizing human cancer microRNAs based on genes' functional consistency between microRNA and cancer. AB - The identification of human cancer-related microRNAs (miRNAs) is important for cancer biology research. Although several identification methods have achieved remarkable success, they have overlooked the functional information associated with miRNAs. We present a computational framework that can be used to prioritize human cancer miRNAs by measuring the association between cancer and miRNAs based on the functional consistency score (FCS) of the miRNA target genes and the cancer-related genes. This approach proved successful in identifying the validated cancer miRNAs for 11 common human cancers with area under ROC curve (AUC) ranging from 71.15% to 96.36%. The FCS method had a significant advantage over miRNA differential expression analysis when identifying cancer-related miRNAs with a fine regulatory mechanism, such as miR-27a in colorectal cancer. Furthermore, a case study examining thyroid cancer showed that the FCS method can uncover novel cancer-related miRNAs such as miR-27a/b, which were showed significantly upregulated in thyroid cancer samples by qRT-PCR analysis. Our method can be used on a web-based server, CMP (cancer miRNA prioritization) and is freely accessible at http://bioinfo.hrbmu.edu.cn/CMP. This time- and cost effective computational framework can be a valuable complement to experimental studies and can assist with future studies of miRNA involvement in the pathogenesis of cancers. PMID- 21976727 TI - A model for Escherichia coli chromosome packaging supports transcription factor induced DNA domain formation. AB - What physical mechanism leads to organization of a highly condensed and confined circular chromosome? Computational modeling shows that confinement-induced organization is able to overcome the chromosome's propensity to mix by the formation of topological domains. The experimentally observed high precision of separate subcellular positioning of loci (located on different chromosomal domains) in Escherichia coli naturally emerges as a result of entropic demixing of such chromosomal loops. We propose one possible mechanism for organizing these domains: regulatory control defined by the underlying E. coli gene regulatory network requires the colocalization of transcription factor genes and target genes. Investigating this assumption, we find the DNA chain to self-organize into several topologically distinguishable domains where the interplay between the entropic repulsion of chromosomal loops and their compression due to the confining geometry induces an effective nucleoid filament-type of structure. Thus, we propose that the physical structure of the chromosome is a direct result of regulatory interactions. To reproduce the observed precise ordering of the chromosome, we estimate that the domain sizes are distributed between 10 and 700 kb, in agreement with the size of topological domains identified in the context of DNA supercoiling. PMID- 21976728 TI - Identification of essential and non-essential single-stranded DNA-binding proteins in a model archaeal organism. AB - Single-stranded DNA-binding proteins (SSBs) play vital roles in all aspects of DNA metabolism in all three domains of life and are characterized by the presence of one or more OB fold ssDNA-binding domains. Here, using the genetically tractable euryarchaeon Haloferax volcanii as a model, we present the first genetic analysis of SSB function in the archaea. We show that genes encoding the OB fold and zinc finger-containing RpaA1 and RpaB1 proteins are individually non essential for cell viability but share an essential function, whereas the gene encoding the triple OB fold RpaC protein is essential. Loss of RpaC function can however be rescued by elevated expression of RpaB, indicative of functional overlap between the two classes of haloarchaeal SSB. Deletion analysis is used to demonstrate important roles for individual OB folds in RpaC and to show that conserved N- and C-terminal domains are required for efficient repair of DNA damage. Consistent with a role for RpaC in DNA repair, elevated expression of this protein leads to enhanced resistance to DNA damage. Taken together, our results offer important insights into archaeal SSB function and establish the haloarchaea as a valuable model for further studies. PMID- 21976729 TI - Opposing effects of DNA on proteolysis of a replication initiator. AB - DNA replication initiation proteins (Reps) are subjected to degradation by cellular proteases. We investigated how the formation of nucleoprotein complex, involving Rep and a protease, affects Rep degradation. All known Escherichia coli AAA+ cytosolic proteases and the replication initiation protein TrfA of the broad host-range plasmid RK2 were used. Our results revealed that DNA influences the degradation process and that the observed effects are opposite and protease specific. In the case of ClpXP and ClpYQ proteases, DNA abolishes proteolysis, while in the case of ClpAP and Lon proteases it stimulates the process. ClpX and ClpY cannot interact with DNA-bound TrfA, while the ClpAP and Lon activities are enhanced by the formation of nucleoprotein complexes involving both the protease and TrfA. Lon has to interact with TrfA before contacting DNA, or this interaction can occur with TrfA already bound to DNA. The TrfA degradation by Lon can be carried out only on DNA. The absence of Lon results with higher stability of TrfA in the cell. PMID- 21976730 TI - Tight cooperation between Mot1p and NC2beta in regulating genome-wide transcription, repression of transcription following heat shock induction and genetic interaction with SAGA. AB - TATA-binding protein (TBP) is central to the regulation of eukaryotic transcription initiation. Recruitment of TBP to target genes can be positively regulated by one of two basal transcription factor complexes: SAGA or TFIID. Negative regulation of TBP promoter association can be performed by Mot1p or the NC2 complex. Recent evidence suggests that Mot1p, NC2 and TBP form a DNA dependent protein complex. Here, we compare the functions of Mot1p and NC2betaduring basal and activated transcription using the anchor-away technique for conditional nuclear depletion. Genome-wide expression analysis indicates that both proteins regulate a highly similar set of genes. Upregulated genes were enriched for SAGA occupancy, while downregulated genes preferred TFIID binding. Mot1p and NC2beta depletion during heat shock resulted in failure to downregulate gene expression after initial activation, which was accompanied by increased TBP and RNA pol II promoter occupancies. Depletion of Mot1p or NC2beta displayed preferential synthetic lethality with the TBP-interaction module of SAGA. Our results support the model that Mot1p and NC2beta directly cooperate in vivo to regulate TBP function, and that they are involved in maintaining basal expression levels as well as in resetting gene expression after induction by stress. PMID- 21976731 TI - Three critical hydrogen bonds determine the catalytic activity of the Diels Alderase ribozyme. AB - Compared to protein enzymes, our knowledge about how RNA accelerates chemical reactions is rather limited. The crystal structures of a ribozyme that catalyzes Diels-Alder reactions suggest a rich tertiary architecture responsible for catalysis. In this study, we systematically probe the relevance of crystallographically observed ground-state interactions for catalytic function using atomic mutagenesis in combination with various analytical techniques. The largest energetic contribution apparently arises from the precise shape complementarity between transition state and catalytic pocket: A single point mutant that folds correctly into the tertiary structure but lacks one H-bond that normally stabilizes the pocket is completely inactive. In the rate-limiting chemical step, the dienophile is furthermore activated by two weak H-bonds that contribute ~7-8 kJ/mol to transition state stabilization, as indicated by the 25 fold slower reaction rates of deletion mutants. These H-bonds are also responsible for the tight binding of the Diels-Alder product by the ribozyme that causes product inhibition. For high catalytic activity, the ribozyme requires a fine-tuned balance between rigidity and flexibility that is determined by the combined action of one inter-strand H-bond and one magnesium ion. A sharp 360 degrees turn reminiscent of the T-loop motif observed in tRNA is found to be important for catalytic function. PMID- 21976732 TI - Clustering RNA structural motifs in ribosomal RNAs using secondary structural alignment. AB - RNA structural motifs are the building blocks of the complex RNA architecture. Identification of non-coding RNA structural motifs is a critical step towards understanding of their structures and functionalities. In this article, we present a clustering approach for de novo RNA structural motif identification. We applied our approach on a data set containing 5S, 16S and 23S rRNAs and rediscovered many known motifs including GNRA tetraloop, kink-turn, C-loop, sarcin-ricin, reverse kink-turn, hook-turn, E-loop and tandem-sheared motifs, with higher accuracy than the state-of-the-art clustering method. We also identified a number of potential novel instances of GNRA tetraloop, kink-turn, sarcin-ricin and tandem-sheared motifs. More importantly, several novel structural motif families have been revealed by our clustering analysis. We identified a highly asymmetric bulge loop motif that resembles the rope sling. We also found an internal loop motif that can significantly increase the twist of the helix. Finally, we discovered a subfamily of hexaloop motif, which has significantly different geometry comparing to the currently known hexaloop motif. Our discoveries presented in this article have largely increased current knowledge of RNA structural motifs. PMID- 21976733 TI - A TetR-like regulator broadly affects the expressions of diverse genes in Mycobacterium smegmatis. AB - Transcriptional regulation plays a critical role in the life cycle of Mycobacterium smegmatis and its related species, M. tuberculosis, the causative microbe for tuberculosis. However, the key transcriptional factors involved in broad regulation of diverse genes remain to be characterized in mycobacteria. In the present study, a TetR-like family transcriptional factor, Ms6564, was characterized in M. smegmatis as a master regulator. A conserved 19 bp palindromic motif was identified for Ms6564 binding using DNaseI footprinting and EMSA. A total of 339 potential target genes for Ms6564 were further characterized by searching the M. smegmatis genome based on the sequence motif. Notably, Ms6564 bound with the promoters of 37 cell cycle and DNA damage/repair genes and regulated positively their expressions. The Ms6564-overexpressed recombinant strain yielded 5-fold lower mutation rates and mutation frequencies, whereas deletion of Ms6564 resulted in ~5-fold higher mutation rates for the mutant strain compared with the wild-type strain. These findings suggested that Ms6564 may function as a global regulator and might be a sensor necessary for activation of DNA damage/repair genes. PMID- 21976734 TI - Label-free high-throughput microRNA expression profiling from total RNA. AB - MicroRNAs (miRNAs) are key biological regulators and promising disease markers whose detection technologies hold great potentials in advancing fundamental research and medical diagnostics. Currently, miRNAs in biological samples have to be labeled before being applied to most high-throughput assays. Although effective, these labeling-based approaches are usually labor-intensive, time consuming and liable to bias. Besides, the cross-hybridization of co-existing miRNA precursors (pre-miRNAs) is not adequately addressed in most assays that use total RNA as input. Here, we present a hybridization-triggered fluorescence strategy for label-free, microarray-based high-throughput miRNA expression profiling. The total RNA is directly applied to the microarray with a short fluorophore-linked oligonucleotide Universal Tag which can be selectively captured by the target-bound probes via base-stacking effects. This Stacking Hybridized Universal Tag (SHUT) assay has been successfully used to analyze as little as 100 ng total RNA from human tissues, and found to be highly specific to homogenous miRNAs. Superb discrimination toward single-base mismatch at the 5' or 3' end has been demonstrated. Importantly, the pre-miRNAs generated negligible signals, validating the direct use of total RNA. PMID- 21976735 TI - Dual targeting of isoleucyl-tRNA synthetase in Trypanosoma brucei is mediated through alternative trans-splicing. AB - Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNAs with their cognate amino acids. They are an essential part of each translation system and in eukaryotes are therefore found in both the cytosol and mitochondria. Thus, eukaryotes either have two distinct genes encoding the cytosolic and mitochondrial isoforms of each of these enzymes or a single gene encoding dually localized products. Trypanosomes require trans-splicing of a cap containing leader sequence onto the 5'-untranslated region of every mRNA. Recently we speculated that alternative trans-splicing could lead to the expression of proteins having amino-termini of different lengths that derive from the same gene. We now demonstrate that alternative trans-splicing, creating a long and a short spliced variant, is the mechanism for dual localization of trypanosomal isoleucyl-tRNA synthetase (IleRS). The protein product of the longer spliced variant possesses an amino-terminal presequence and is found exclusively in mitochondria. In contrast, the shorter spliced variant is translated to a cytosol specific isoform lacking the presequence. Furthermore, we show that RNA stability is one mechanism determining the differential abundance of the two spliced isoforms. PMID- 21976736 TI - RNA-seq analysis of small RNPs in Trypanosoma brucei reveals a rich repertoire of non-coding RNAs. AB - The discovery of a plethora of small non-coding RNAs (ncRNAs) has fundamentally changed our understanding of how genes are regulated. In this study, we employed the power of deep sequencing of RNA (RNA-seq) to examine the repertoire of ncRNAs present in small ribonucleoprotein particles (RNPs) of Trypanosoma brucei, an important protozoan parasite. We identified new C/D and H/ACA small nucleolar RNAs (snoRNAs), as well as tens of putative novel non-coding RNAs; several of these are processed from trans-spliced and polyadenylated transcripts. The RNA seq analysis provided information on the relative abundance of the RNAs, and their 5'- and 3'-termini. The study demonstrated that three highly abundant snoRNAs are involved in rRNA processing and highlight the unique trypanosome specific repertoire of these RNAs. Novel RNAs were studied using in situ hybridization, association in RNP complexes, and 'RNA walk' to detect interaction with their target RNAs. Finally, we showed that the abundance of certain ncRNAs varies between the two stages of the parasite, suggesting that ncRNAs may contribute to gene regulation during the complex parasite's life cycle. This is the first study to provide a whole-genome analysis of the large repertoire of small RNPs in trypanosomes. PMID- 21976737 TI - Protein Data Bank Japan (PDBj): maintaining a structural data archive and resource description framework format. AB - The Protein Data Bank Japan (PDBj, http://pdbj.org) is a member of the worldwide Protein Data Bank (wwPDB) and accepts and processes the deposited data of experimentally determined macromolecular structures. While maintaining the archive in collaboration with other wwPDB partners, PDBj also provides a wide range of services and tools for analyzing structures and functions of proteins, which are summarized in this article. To enhance the interoperability of the PDB data, we have recently developed PDB/RDF, PDB data in the Resource Description Framework (RDF) format, along with its ontology in the Web Ontology Language (OWL) based on the PDB mmCIF Exchange Dictionary. Being in the standard format for the Semantic Web, the PDB/RDF data provide a means to integrate the PDB with other biological information resources. PMID- 21976738 TI - Absence of glomerular IgG4 deposition in patients with membranous nephropathy may indicate malignancy. AB - BACKGROUND: The renal pathological manifestations of malignancy-associated membranous nephropathy (M-MN) and idiopathic membranous nephropathy (I-MN) are similar. It has been suggested that glomerular IgG4 deposition may play an important role in the pathogenesis of I-MN. In the present study, we compared the IgG subclass of immune complex deposition, clinical data and pathological data of patients with M-MN and I-MN. METHODS: Eight patients with M-MN and 42 patients with I-MN diagnosed between 1997 and 2009 in our hospital were enrolled. The clinical and pathological data were retrospectively collected, and glomerular IgG subclass deposition was detected by immunohistochemistry. RESULTS: Patients with M-MN were older (P = 0.003), with lower serum albumin (P = 0.034) and higher serum C-reactive protein (CRP) level (P = 0.003) than patients with I-MN. The majority of patients with M-MN had earlier pathological stages (P = 0.003) and less IgG deposition in glomeruli (P = 0.029). Absence of IgG4 deposition in glomeruli was notably observed in patients with M-MN (7/8 in M-MN versus 6/42 in I-MN, P < 0.001) and it was an independent predictor for occurrence of malignancy (hazard ratio 0.065, 95% confidence intervals 0.007-0.571, P = 0.014). CONCLUSION: Absence of glomerular IgG4 deposition, together with older age, severe hypoalbuminemia and high serum CRP level could be useful clues to differentiate M-MN from I-MN. PMID- 21976739 TI - Important differences in management policies for children with end-stage renal disease in the Netherlands and Belgium--report from the RICH-Q study. AB - BACKGROUND: The low prevalence of childhood end-stage renal disease and the small centre sizes have been a barrier for clinical studies and the development of evidence-based guidelines for chronic renal replacement therapy (cRRT) in children. Few data exist on the quality of care for these patients and the applicability of existing guidelines. The aim of this study is to quantify variation in treatment policies and actually delivered care in nine centres that deliver cRRT for children. METHODS: We surveyed treatment policies in all nine centres in the Netherlands and Belgium and compared them with the actually provided therapies and with recommendations from available guidelines. Data on treatment policies were gathered by questionnaires; actually provided care and outcomes were registered prospectively from 2007 to 2010. RESULTS: Data on policies and actual patient care were obtained from all nine centres. We found relevant differences between centres in treatment policies on various topics, e.g. estimated glomerular filtration rate threshold as an indication for initiation of cRRT, preferred initial mode of cRRT, peritoneal dialysis catheter care, haemodialysis frequency and vascular access. Discrepancies were seen between stated treatment policies and actual performed therapies. For the majority of policies, no evidence-based guidelines are available. CONCLUSIONS: Health care disparities exist due to large and unwanted variation in treatment policies between hospitals providing cRRT for children. Delivered care does not live up to stated policies, for which clear and internationally accepted guidelines are lacking. PMID- 21976740 TI - Sequential maintenance therapy with cyclosporin A and mycophenolate mofetil for sustained remission of childhood steroid-resistant nephrotic syndrome. AB - BACKGROUND: There is currently no established standard for maintenance therapy of steroid-resistant nephrotic syndrome (SRNS). We report the long-term clinical course, medication, pharmacokinetic data, and renal function of 23 children with primary, non-familial SRNS with focal segmental glomerulosclerosis (FSGS). METHODS: To achieve initial remission, patients were treated with high-dose intravenous (i. v.) methylprednisolone and oral cyclosporin A (CsA). Maintenance therapy included transient alternate day oral prednisolone, CsA and angiotensin converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers. In 18 patients, mycophenolate mofetil (MMF) (adjusted to achieve blood mycophenolic acid trough concentrations > 2 MUg/mL) was sequentially added, and 16 patients were converted to MMF monotherapy. RESULTS: During a mean follow-up time of 7.0 years (1.7-16.5 years; cumulative observation time 161 patient-years), sustained remission could be achieved in all patients. Five of 23 patients (21%) experienced 10 relapses; all responded to relapse therapy. Maintenance therapy could be permanently discontinued in seven patients (30%). After conversion from CsA to MMF, renal function improved significantly; the eGFR at last follow-up was 137 (range 106-198) mL/min * 1.73 m(2). The mean number of anti-hypertensive drugs decreased from 1.86 per patient after initial remission to 0.57 on MMF monotherapy (P < 0.002). CONCLUSIONS: The data of this uncontrolled retrospective study indicate that in children with SRNS/FSGS achieving initial remission, a sequential steroid-free therapy consisting of a combination of CsA and MMF followed by MMF alone (with the addition of ACE inhibitors and angiotensin receptor blockers), can provide sustained long-term remission, preservation of renal function and better control of blood pressure. PMID- 21976741 TI - Angiopoietin-2 levels predict mortality in CKD patients. AB - BACKGROUND: The pathophysiology of aggravated atherosclerosis in chronic kidney disease (CKD) is still incompletely understood. However, there is an increasing focus on non-traditional risk factors, including endothelial dysfunction. Angiopoietin-2 (Ang-2) impairs endothelial function by inhibiting the binding of Angiopoietin-1 (Ang-1) to their shared receptor Tie2 and is increased in diabetes, hypertension, coronary heart disease and CKD. Furthermore, Ang-2 levels are associated with the prevalent vascular burden of CKD patients. Thus, we aimed to investigate its impact on outcome in CKD, the population most likely to die of cardiovascular events. METHODS: We prospectively studied 128 CKD patients [43 CKD Stage 4, 85 CKD Stage 5 (57 haemodialysis, 28 peritoneal dialysis)] over a follow up period of 4 years. Biochemical and clinical parameters, including objective scoring of vascular calcification (VC) by computed tomography (CT) and arterial stiffness by applanation tonometry (including radial-dorsalis pedis pulse wave velocity (PWVrd)) were recorded. Baseline Ang-1 [enzyme-linked immunosorbent assay (ELISA)], Ang-2 [immunoluminometric assay (ILMA)] and soluble Tie2 (sTie2) (ELISA) levels were measured in this group as well as in 20 healthy controls. RESULTS: Ang-2 values were significantly higher in CKD patients than in controls (2.01 +/- 0.94 versus 1.00 +/- 0.47 ng/mL, P < 0.0001). Furthermore, Ang-2 was significantly higher in dialysis than in Stage 4 CKD patients and correlated with markers of vascular disease [cholesterol, hsCRP, osteoprotegerin (OPG)]. However, elevated Ang-2 was not associated with the degree of VC or with arterial stiffness. Cox-regression analysis detected Ang-2 as an independent predictor of mortality in both unadjusted [hazard ratio (HR) 1.15; P = 0.002] and models adjusted for age and VC (HR 1.14; P = 0.003). CONCLUSIONS: Ang-2 levels are associated with systemic markers/mediators of micro-inflammation in CKD patients. Furthermore, elevated Ang-2 levels are strong predictors of long-term mortality, independent of conduit arterial stiffness or VC. PMID- 21976743 TI - Approach to the patient with persistent or recurrent primary hyperparathyroidism. AB - Reoperative parathyroid surgery may be required in patients who have persistent primary hyperparathyroidism after an unsuccessful operation and in patients who had an initially successful exploration but develop recurrent disease at an interval greater than 6 months postoperatively. Additionally, patients who have had significant surgery in the cervical region, particularly total thyroidectomy, should be considered in this group because they pose identical technical challenges that in the past have resulted in suboptimal cure and complication rates. These patients require a meticulous review of their historical, biochemical, imaging, and operative data to confirm the diagnosis, to evaluate the possibility of familial forms of hyperparathyroidism, and to confirm the indications for surgery. Once a patient is deemed an appropriate surgical candidate, sequential imaging is required to yield a roadmap to guide surgical intervention. These reoperative procedures require an experienced parathyroid surgeon armed with intraoperative adjuncts to locate the offending parathyroid gland(s) and remove them while minimizing collateral injury, particularly to the recurrent laryngeal nerves. These patients are also at increased risk of postoperative hypocalcemia that can be life-threatening. Despite these concerns, an experienced endocrine team can diagnose persistent or recurrent hyperparathyroidism, localize residual abnormal parathyroid glands, and perform surgical intervention with success and complication profiles that approximate those achieved in the unexplored patient. PMID- 21976744 TI - Approach to the diagnosis and treatment of neonatal hypothyroidism. AB - Congenital hypothyroidism, occurring in 1:3000 newborns, is one of the most common preventable causes of mental retardation. Neurodevelopmental outcome is inversely related to the age of diagnosis and treatment. Infants detected through newborn screening programs and started on l-T(4) in the first few weeks of life have a normal or near-normal neurodevelopmental outcome. The recommended starting dose of l-T(4) (10-15 MUg/kg . d) is higher on a weight basis than the dose for children and adults. Tailoring the starting l-T(4) dose to the severity of the hypothyroidism will normalize serum T(4) and TSH as rapidly as possible. It is important to obtain confirmatory serum thyroid function tests before treatment is started. Further diagnostic studies, such as radionuclide uptake and scan and ultrasonography, may be performed to determine the underlying cause of hypothyroidism. Because results from these tests generally do not alter the initial treatment decision, however, these diagnostic studies are rarely indicated. The developing brain has a critical dependence on thyroid hormone for the first 2-3 yr of life; thus, monitoring occurs at more frequent intervals than in older children and adults. Serum free T(4) and TSH should be checked at intervals frequent enough to ensure timely adjustment of l-T(4) dosing and to keep serum free T(4) and TSH levels in target ranges. Given the success of early detection and treatment of neonates with congenital hypothyroidism, a public health mandate should be to develop similar programs for the 75% of babies worldwide who are born in areas without newborn screening programs. PMID- 21976742 TI - Endocrine dysregulation in anorexia nervosa update. AB - CONTEXT: Anorexia nervosa is a primary psychiatric disorder with serious endocrine consequences, including dysregulation of the gonadal, adrenal, and GH axes, and severe bone loss. This Update reviews recent advances in the understanding of the endocrine dysregulation observed in this state of chronic starvation, as well as the mechanisms underlying the disease itself. EVIDENCE ACQUISITION: Findings of this update are based on a PubMed search and the author's knowledge of this field. EVIDENCE SYNTHESIS: Recent studies have provided insights into the mechanisms underlying endocrine dysregulation in states of chronic starvation as well as the etiology of anorexia nervosa itself. This includes a more complex understanding of the pathophysiologic bases of hypogonadism, hypercortisolemia, GH resistance, appetite regulation, and bone loss. Nevertheless, the etiology of the disease remains largely unknown, and effective therapies for the endocrine complications and for the disease itself are lacking. CONCLUSIONS: Despite significant progress in the field, further research is needed to elucidate the mechanisms underlying the development of anorexia nervosa and its endocrine complications. Such investigations promise to yield important advances in the therapeutic approach to this disease as well as to the understanding of the regulation of endocrine function, skeletal biology, and appetite regulation. PMID- 21976745 TI - Continuous glucose monitoring: an Endocrine Society Clinical Practice Guideline. AB - OBJECTIVE: The aim was to formulate practice guidelines for determining settings where patients are most likely to benefit from the use of continuous glucose monitoring (CGM). PARTICIPANTS: The Endocrine Society appointed a Task Force of experts, a methodologist, and a medical writer. EVIDENCE: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. CONSENSUS PROCESS: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of The Endocrine Society, the Diabetes Technology Society, and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. CONCLUSIONS: The Task Force evaluated three potential uses of CGM: 1) real-time CGM in adult hospital settings; 2) real-time CGM in children and adolescent outpatients; and 3) real-time CGM in adult outpatients. The Task Force used the best available data to develop evidence-based recommendations about where CGM can be beneficial in maintaining target levels of glycemia and limiting the risk of hypoglycemia. Both strength of recommendations and quality of evidence were accounted for in the guidelines. PMID- 21976746 TI - Acute suppurative thyroiditis treated avoiding invasive procedures in a child. PMID- 21976747 TI - Vitamin D recommendations: the saga continues. PMID- 21976752 TI - The Hormone Foundation's: Patient guide to continuous glucose monitoring. PMID- 21976753 TI - Original findings associated with two cases of bovine papular stomatitis. AB - Bovine papular stomatitis virus was isolated from two calves in an animal house with biosafety level 3 confinement. The hypotheses on the origin of the infection, the interesting features of the partial amino acid sequences of the major envelope viral protein, and the importance of diagnostic tools available for animal diseases that are not listed by the World Organization for Animal Health (OIE) are discussed. PMID- 21976754 TI - Actinobaculum bacteremia: a report of 12 cases. AB - Actinobaculum species are anaerobic Gram-positive rods that have previously been associated with urinary tract infection (UTI) in the elderly. We report 12 patients with Actinobaculum bacteremia. Only 40% of blood cultures were clinically considered significant by the treating physicians, but most patients were treated for UTI, suggesting a possible urinary source of bacteremia. Clinicians should be aware of the pathogenic potential of Actinobaculum spp. PMID- 21976756 TI - Multiplex PCR method for detection of Clostridium difficile tcdA, tcdB, cdtA, and cdtB and internal in-frame deletion of tcdC. AB - A multiplex PCR method was developed for the detection of Clostridium difficile toxin genes tcdA, tcdB, ctdA, and cdtB and the major in-frame deletion types (18, 39, and 54 bp) of tcdC. The method has high specificity for PCR ribotype 027 and may identify other C. difficile strains of clinical and epidemiological importance. PMID- 21976757 TI - Molecular detection and species-specific identification of medically important Aspergillus species by real-time PCR in experimental invasive pulmonary aspergillosis. AB - Diagnosis of invasive pulmonary aspergillosis (IPA) remains a major challenge to clinical microbiology laboratories. We developed rapid and sensitive quantitative PCR (qPCR) assays for genus- and species-specific identification of Aspergillus infections by use of TaqMan technology. In order to validate these assays and understand their potential diagnostic utility, we then performed a blinded study of bronchoalveolar lavage (BAL) fluid specimens from well-characterized models of IPA with the four medically important species. A set of real-time qPCR primers and probes was developed by utilizing unique ITS1 regions for genus- and species specific detection of the four most common medically important Aspergillus species (Aspergillus fumigatus, A. flavus, A. niger, and A. terreus). Pan Aspergillus and species-specific qPCRs with BAL fluid were more sensitive than culture for detection of IPA caused by A. fumigatus in untreated (P < 0.0007) and treated (P <= 0.008) animals, respectively. For infections caused by A. terreus and A. niger, culture and PCR amplification from BAL fluid yielded similar sensitivities for untreated and treated animals. Pan-Aspergillus PCR was more sensitive than culture for detection of A. flavus in treated animals (P = 0.002). BAL fluid pan-Aspergillus and species-specific PCRs were comparable in sensitivity to BAL fluid galactomannan (GM) assay. The copy numbers from the qPCR assays correlated with quantitative cultures to determine the pulmonary residual fungal burdens in lung tissue. Pan-Aspergillus and species-specific qPCR assays may improve the rapid and accurate identification of IPA in immunocompromised patients. PMID- 21976758 TI - Rapid, simple, and sensitive detection of Anaplasma phagocytophilum by loop mediated isothermal amplification of the msp2 gene. AB - Anaplasma phagocytophilum is the causative agent of human granulocytic anaplasmosis, which is prevalent throughout China. In this study, we describe a rapid, simple, and sensitive loop-mediated isothermal amplification (LAMP) assay targeting the msp2 gene of A. phagocytophilum that is ideal for application in rural areas in China. This assay has the potential to detect A. phagocytophilum early in infection as an alternative to existing methods. A total of 42 suspected cases of infection with A. phagocytophilum, 15 serologically confirmed and 27 probable cases, were analyzed by the msp2 LAMP assay. To validate the accuracy of LAMP, previously established nested-PCR and real-time PCR assays were utilized. The sensitivity of LAMP was 25 copies per reaction (approximately 1,250 copies per ml blood) for A. phagocytophilum, and the assay did not detect false positives among 27 members of the order Rickettsiales and 17 common clinical pathogens. To evaluate the clinical applicability of the LAMP assay, a total of 42 clinical samples were examined. A positive LAMP result was obtained for 12 of the confirmed cases and for 14 of 27 suspected cases, while only 1 confirmed case and 3 cases (2 confirmed cases and 1 suspected case) were detected by nested PCR and real-time PCR, respectively. The LAMP assay described in this study demonstrated a high level of sensitivity comparable with that of nested PCR and real-time PCR for the detection of A. phagocytophilum. This LAMP assay is a valuable method for rapid, cost-effective, and simple detection of A. phagocytophilum in the rural areas of China. PMID- 21976755 TI - Widespread occurrence of diverse human pathogenic types of the fungus Fusarium detected in plumbing drains. AB - It has been proposed that plumbing systems might serve as a significant environmental reservoir of human-pathogenic isolates of Fusarium. We tested this hypothesis by performing the first extensive multilocus sequence typing (MLST) survey of plumbing drain-associated Fusarium isolates and comparing the diversity observed to the known diversity of clinical Fusarium isolates. We sampled 471 drains, mostly in bathroom sinks, from 131 buildings in the United States using a swabbing method. We found that 66% of sinks and 80% of buildings surveyed yielded at least one Fusarium culture. A total of 297 isolates of Fusarium collected were subjected to MLST to identify the phylogenetic species and sequence types (STs) of these isolates. Our survey revealed that the six most common STs in sinks were identical to the six most frequently associated with human infections. We speculate that the most prevalent STs, by virtue of their ability to form and grow in biofilms, are well adapted to plumbing systems. Six major Fusarium STs were frequently isolated from plumbing drains within a broad geographic area and were identical to STs frequently associated with human infections. PMID- 21976759 TI - Optimized pathogen detection with 30- compared to 20-milliliter blood culture draws. AB - Using data from 23,313 patients, we assessed whether two blood culture sets of three bottles per set would detect more pathogens than two sets of two bottles per set and achieve similar sensitivity to collecting three sets of two bottles per set. We also compared the yield of aerobic and anaerobic bottles. Thirty milliliters of blood was distributed to one anaerobic and two aerobic bottles. Among 26,855 collections of >= 60 ml within 30 min, 1,379 (5.1%) were positive for a pathogen not requiring detection in more than one set to be considered a pathogen, with 72 additional distinct pathogens detected using two 30-ml compared to two 20-ml sets of one aerobic and one anaerobic bottle (increased yield, 7.9%; 95% confidence interval [CI], 6.2 to 9.8%). For conditional pathogens requiring detection in at least two positive blood cultures for classification as pathogens (i.e., otherwise classified as contaminants), there were 162 positive detections with two 30-ml sets, of which 16 would not have been detected by two 20-ml sets (increased yield, 11.0% [95% CI, 6.4 to 17.2%]). Among 134 subjects who had three sets of 30 ml each within a 30-min interval, there was complete concordance between 60 ml of blood drawn in the first two sets of 30 ml and three 20-ml sets (P = 1.0). One aerobic bottle plus one anaerobic bottle yielded more pathogens than two aerobic bottles for organisms requiring a single (P < 0.001) and two (P = 0.04) positive sets to be defined as pathogens. In conclusion, we showed that collection of two aerobic and one anaerobic blood culture bottles per set results in improved yield compared to two bottles per set. We also confirmed that an anaerobic bottle should be included in blood culture sets. PMID- 21976760 TI - Galactomannan antigenemia after infusion of gluconate-containing Plasma-Lyte. AB - We demonstrated that sodium gluconate was the factor causing false-positive galactomannan (GM) antigenemia of Plasma-Lyte hydration solution. Infusion of sodium gluconate-containing solution but not gluconate-free Plasma-Lyte resulted in positive serum GM antigenemia. Serum GM concentrations also correlated with the volume and in vitro concentrations of GM within gluconate-containing solutions of infused Plasma-Lyte. PMID- 21976761 TI - Novel one-step method for detection and isolation of active-toxin-producing Clostridium difficile strains directly from stool samples. AB - The alarming emergence of hypervirulent strains of Clostridium difficile with increased toxin production, severity of disease, morbidity, and mortality emphasizes the need for a culture method that permits simultaneous isolation and detection of virulent strains. The C. difficile toxins A and B are critical virulence factors, and strains can either be toxin-producing (virulent) or non toxin-producing (nonvirulent). Strains that are isolated from human infections generally produce either toxin A or toxin B or both. The methods currently available for culturing C. difficile do not differentiate strains that produce active toxins from strains that do not produce toxins or produce inactive toxins. As a result, the identification and isolation of toxin-producing strains from stool is currently a two-step process. First, the stool is plated on a selective medium, and then suspected colonies are analyzed for toxin production or the presence of the toxin genes. We describe here a novel selective and differential culture method, the Cdifftox plate assay, which combines in a single step the specific isolation of C. difficile strains and the detection of active toxin. This assay was developed based on our recent finding that the A and B toxins of C. difficile cleave chromogenic substrates that have stereochemical characteristics similar to their natural substrate, UDP-glucose. The Cdifftox plate assay is shown here to be extremely accurate (99.8% effective) in detecting toxin-producing strains through the analysis of 528 C. difficile isolates selected from 50 tissue culture cytotoxicity assay-positive clinical stool samples. The Cdifftox plate assay advances and improves the culture approach such that only C. difficile strains will grow on this agar, and virulent strains producing active toxins can be differentiated from nonvirulent strains, which do not produce active toxins. This new method reduces the time and effort required to isolate and confirm toxin-producing C. difficile strains. PMID- 21976762 TI - Malaria hidden in a patient with diffuse large-B-cell lymphoma and sickle-cell trait. AB - We report a case of an African patient with sickle cell trait who was diagnosed in Spain with B-cell lymphoma. Blood smears were negative for malaria, and no plasmodium antigens were detected in the blood. To treat his lymphoma, the patient underwent chemotherapy and autologous stem cell transplantation. Following a splenectomy due to a worsening condition, he developed clinical malaria with detectable parasitemia. This case suggests that the humoral response and parasite removal by the spleen may afford protection from overt disease and may even help maintain subclinical human reservoirs of the disease. PMID- 21976763 TI - Molecular characterization of quinolone-resistant Neisseria gonorrhoeae isolates from Brazil. AB - Despite the rapid spread of antibiotic resistance among gonococci worldwide, limited reports are available from Brazilian locations. In the present study, 25 quinolone-resistant Neisseria gonorrhoeae (QRNG) strains isolated in Rio de Janeiro, Brazil, were characterized by phenotypic and molecular methods, including analysis of mutations in the gyrA and parC genes. They represented 16.5% of the N. gonorrhoeae isolates obtained during a survey performed from 2006 to 2010. A trend for increasing resistance to ciprofloxacin was observed in the period investigated. The most prevalent pattern of mutation observed among QRNG isolates, Ser-91 to Phe and Asp-95 to Gly in gyrA and Ser-87 to Arg in parC, was detected in 40% of the isolates exhibiting MICs ranging from 4 to >32 MUg/ml. Rare types of mutations were found in the gyrA gene (Gln-102 to His [12%] and Asp 95 to Tyr [4%]) and in the parC gene (Ser-88 to Thr [4%]). The genetic relationship of the QRNG isolates, evaluated by pulsed-field gel electrophoresis, suggested that the increase in the frequencies of the QRNG isolates in Rio de Janeiro, Brazil, may have arisen as a result of simultaneous spread of two clonal groups. The results also indicate that fluoroquinolones may no longer be used as first line antibiotics for the treatment of gonorrhea in Rio de Janeiro, and that programs for antimicrobial susceptibility surveillance of N. gonorrhoeae should also be implemented in other regions of Brazil. PMID- 21976764 TI - Epidemiology of invasive Streptococcus pyogenes infections in France in 2007. AB - Invasive group A streptococcal (GAS) infections cause significant morbidity and mortality. A national survey was initiated to assess the burden of invasive GAS infections in France, describe their clinical characteristics, and assess the molecular characteristics of GAS strains responsible for these infections. The survey was conducted in 194 hospitals, accounting for 51% of acute care hospital admissions in France. Clinical data, predisposing factors, and demographic data were obtained, and all GAS isolates were emm sequence typed. We identified 664 cases of invasive GAS infections, with an annual incidence of 3.1 per 100,000 population. The case-fatality ratio was 14% and rose to 43% in the case of streptococcal toxic shock syndrome. Bacteremia without identified focus (22%) and skin/soft tissue infections (30%) were the most frequent clinical presentations. Necrotizing fasciitis was frequent in adults (18%) and uncommon in children (3%). The 3 predominant emm types were emm1, emm89, and emm28, accounting for 33%, 16%, and 10% of GAS isolates, respectively. The emm1 type was associated with fatal outcomes and was more frequent in children than in adults. Six clusters of cases were identified, with each cluster involving 2 invasive cases due to GAS strains which shared identical GAS emm sequence types. Four clusters of cases involved eight postpartum infections, one family cluster involved a mother and child, and one cluster involved two patients in a nursing home. Invasive GAS infection is one of the most severe bacterial diseases in France, particularly in persons aged >= 50 years or when associated with toxic shock syndrome. PMID- 21976765 TI - A novel flucytosine-resistant yeast species, Candida pseudoaaseri, causes disease in a cancer patient. AB - Some members of the genus Candida are among the most common human fungal pathogens and cause serious diseases especially in immunocompromised people. A yeast was isolated from a blood culture from an immunocompromised cancer patient who suffered from acute pneumonia. The growth characteristics of the yeast on CHROMagar Candida were similar to those of Candida tropicalis, whereas the API ID 32C system identified the yeast as Candida silvicola. On the basis of the nucleotide divergence in the D1/D2 domain of the 26S nuclear rRNA (nrRNA) gene, as well as the internal transcribed spacer (ITS) domain of the nrRNA gene region, a new species, Candida pseudoaaseri sp. nov. with type strain VK065094 (CBS 11170(T)), which was found to be closely related to Candida aaseri, is proposed. While C. aaseri strains were susceptible to all tested antifungals, the new species is resistant to flucytosine and may also be distinguished from C. aaseri by its ability to assimilate l-rhamnose, whereas its colony morphology on CHROMagar Candida may be helpful for differentiation. PMID- 21976766 TI - Staphylococcus haemolyticus as an important hospital pathogen and carrier of methicillin resistance genes. AB - Phenotypic and molecular methods were used to characterize the antibiotic resistance of 64 clinical isolates of Staphylococcus haemolyticus. By PCR of the mecA gene, 87% were found to be methicillin resistant. Approximately 55% harbored staphylococcal cassette chromosome mec element (SCCmec) type V, and only one SCCmec type IV. Many isolates (75%) displayed multiresistance, and pulsotype analysis showed a high diversity. PMID- 21976767 TI - Dried culture spots for Xpert MTB/RIF external quality assessment: results of a phase 1 pilot study in South Africa. AB - Implementation of Xpert MTB/RIF requires quality assessment. A pilot program using dried culture spots (DCSs) of inactivated Mycobacterium tuberculosis is described. Of 274 DCS results received, 2.19% generated errors; the remainder yielded 100% correct Mycobacterium tuberculosis detection. The probe A cycle threshold (C(T)) variability of three DCS batches was <= 3.47. The study of longer-term DCS stability is ongoing. PMID- 21976768 TI - Confirmation and follow-up of neurocysticercosis by real-time PCR in cerebrospinal fluid samples of patients living in France. AB - Neurocysticercosis diagnosis is based on a combination of clinical, epidemiological, radiological, and immunological findings. We describe a real time PCR assay for the confirmation of neurocysticercosis diagnosis in cerebrospinal fluid. The assay, tested on samples from nine patients living in France and diagnosed with neurocysticercosis, had a detection rate of 83.3% and 100% specificity. PMID- 21976769 TI - Detection of Staphylococcus aureus isolates with heterogeneous intermediate-level resistance to vancomycin in the United States. AB - The prevalence of heterogeneous intermediate-level resistance to vancomycin (hVISA) in Staphylococcus aureus was assessed by screening a large collection of recent isolates. Susceptibility testing by the Clinical and Laboratory Standards Institute broth microdilution method and the Etest GRD (glycopeptide resistance detection) method (bioMerieux) was performed on 4,210 clinically significant S. aureus isolates obtained in 2009 from 43 U.S. centers. Isolates with Etest GRD positive results for hVISA were evaluated further by repeat GRD testing and population analysis profiling-area under the curve (PAP-AUC) analysis. No VISA (vancomycin MIC, 4 to 8 MUg/ml) or vancomycin-resistant (MIC >= 16 MUg/ml) strains were detected. The Etest GRD screen for hVISA was initially positive for 68 isolates (1.6%; all by teicoplanin MIC >= 8 MUg/ml at 24 or 48 h). Among those 68 isolates, 45 were reproducibly GRD positive. PAP-AUC testing confirmed only 11 isolates as hVISA (all had reproducible GRD-positive results). The 11 hVISA isolates were from nine medical centers and appeared genetically diverse (ten different PFGE types). The rates of resistance (including intermediate) for hVISA were as follows: oxacillin, 82%; erythromycin, 82%; clindamycin, 73%; levofloxacin, 73%; trimethoprim-sulfamethoxazole, 9%; and daptomycin, 9%. All hVISA isolates were susceptible to linezolid, tigecycline, and ceftaroline. Our data suggest that the overall prevalence of hVISA in the United States is low (0.3%). The hVISA isolates represented 10.5% of isolates with vancomycin MICs of 2 MUg/ml and 0.1% of isolates with vancomycin MICs of 1 MUg/ml. The positive predictive value of GRD Etest for hVISA was 16.2% for initial screen positive and 24.4% for reproducibly positive results. PMID- 21976770 TI - Two SERK genes are markers of pluripotency in Cyclamen persicum Mill. AB - The genetic basis of stem cell specification in somatic embryogenesis and organogenesis is still obscure. SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE (SERK) genes are involved in embryogenesis and organogenesis in numerous species. In vitro culture of Cyclamen persicum immature ovules provides a system for investigating stem cell formation and maintenance, because lines forming either organs or embryos or callus without organs/embryos are available for the same cultivar and plant growth regulator conditions. The present aim was to exploit this property of cyclamen cultures to understand the role of SERK(s) in stem cell formation and maintenance in somatic embryogenesis and organogenesis in vitro, in comparison with expression in planta. CpSERK1 and CpSERK2 were isolated from embryogenic callus. CpSERK1 and CpSERK2 levels by RT-PCR showed that expression is high in embryogenic, moderate in organogenic, and null in recalcitrant calli. in situ hybridizations showed that the expression of both genes started in clumps of pluripotent stem cells, from which both pre-embryogenic aggregates and organ meristemoids derived, and continued in their trans-amplifying, meristem-like, derivatives. Expression declined in organ meristemoids, in parallel with a partial loss of meristematization. In mature somatic embryos, and in shoot and root primordia, CpSERK1 and CpSERK2 were expressed in meristems, and similar patterns occurred in zygotic embryo and primary meristems in planta. The results point to SERK1 and SERK2 as markers of pluripotency in cyclamen. It is proposed that the high expression of these genes in the trans-amplifying derivatives of the stem cells maintains a pluripotent condition leading to totipotency and, consequently, somatic embryogenesis. PMID- 21976771 TI - The roles of the cation transporters CHX21 and CHX23 in the development of Arabidopsis thaliana. AB - The Arabidopsis thaliana genome encodes a family of 28 proteins whose members have been associated with the transport of monovalent cations across membranes. Experiments have been performed to elucidate the biochemical function and the role in plant development of two closely related members of this CHX family. A genotype carrying a knockout of the AtCHX23 gene (At1g05580) showed no phenotype when grown in glasshouse conditions. In particular, it did not exhibit the reduced root growth phenotype observed for a knockout of its homologue AtCHX21 when exposed to elevated sodium concentration. However, it was not possible to produce plants that were homozygous knockout for both AtCHX21 and AtCHX23. Reverse transcription-PCR (RT-PCR) experiments revealed that both genes are highly expressed in flower buds, flowers, and pollen. However, examination of pollen grain viability and pollen tube growth through excised styles did not reveal a phenotypic difference between the chx21(-)chx23(-) condition and other haplotypes. Crosses between selected mutants and wild-type plants in which the chx21(-)chx23(-) haplotype was produced by either the male or female parent demonstrated unequivocally that the chx21(-)chx23(-) haplotype could not pass through the female line. This suggests that the genes share a critical function in the development and/or function of the female gametophyte and that this function cannot be provided by other members of the AtCHX gene family. Experiments were carried out using the heterologous expression of AtCHX23 in Saccharomyces cerevisiae genotypes carrying combinations of deletions of genes involved in the transport of sodium or potassium across membranes. The results show that CHX23 would only complement the poor colony growth phenotype associated with the deletion of the yeast gene kha1. The conclusion is that both AtCHX21 and AtCHX23 act in potassium homeostasis within the female gametophyte and this is discussed in terms of the diversification of gene sequence and function within the CHX gene family. PMID- 21976772 TI - Microsatellite genetic structure and cytonuclear discordance in naturally fragmented populations of deer mice (Peromyscus maniculatus). AB - The Great Lakes impose high levels of natural fragmentation on local populations of terrestrial animals in a way rarely found within continental ecosystems. Although separated by major water barriers, woodland deer mouse (Peromyscus maniculatus gracilis) populations on the islands and on the Upper Peninsula (UP) and Lower Peninsula (LP) of Michigan have previously been shown to have a mitochondrial DNA contact zone that is incongruent with the regional landscape. We analyzed 11 microsatellite loci for 16 populations of P. m. gracilis distributed across 2 peninsulas and 6 islands in northern Michigan to address the relative importance of geographical structure and inferred postglacial colonization patterns in determining the nuclear genetic structure of this species. Results showed relatively high levels of genetic structure for this species and a significant correlation between interpopulation differentiation and separation by water but little genetic structure and no isolation-by-distance within each of the 2 peninsulas. Genetic diversity was generally high on both peninsulas but lower and correlated to island size in the Beaver Island Archipelago. These results are consistent with the genetic and demographic isolation of Lower Peninsula populations, which is a matter of concern given the dramatic decline in P. m. gracilis abundance on the Lower Peninsula in recent years. PMID- 21976773 TI - Ly6G+ neutrophils are dispensable for defense against systemic Listeria monocytogenes infection. AB - Listeria monocytogenes is a facultative intracellular bacterium that causes systemic infections in immunocompromised hosts. Early recruitment of myeloid cells, including inflammatory monocytes and neutrophils, to sites of L. monocytogenes infection is essential for the control of infection and host survival. Because previous experimental studies used depleting or blocking Abs that affected both inflammatory monocytes and neutrophils, the relative contributions of these cell populations to defense against L. monocytogenes infection remain incompletely defined. In this article, we used highly selective depletion strategies to either deplete inflammatory monocytes or neutrophils from L. monocytogenes-infected mice and demonstrate that neutrophils are dispensable for early and late control of infection. In contrast, inflammatory monocytes are essential for bacterial clearance during the innate and adaptive phases of the immune response to L. monocytogenes infection. PMID- 21976774 TI - Antigen-fixed leukocytes tolerize Th2 responses in mouse models of allergy. AB - Allergic diseases, including asthma and food allergies, are an increasing health concern. Immunotherapy is an effective therapeutic approach for many allergic diseases but requires long dose escalation periods and has a high risk of adverse reactions, particularly in food allergy. New methods to safely induce Ag-specific tolerance could improve the clinical approach to allergic disease. We hypothesized that Ag-specific tolerance induced by the i.v. injection of Ags attached to the surface of syngeneic splenic leukocytes (Ag-coupled splenocytes [Ag-SPs]) with the chemical cross-linking agent ethylene-carbodiimide, which effectively modulate Th1/Th17 diseases, may also safely and efficiently induce tolerance in Th2-mediated mouse models of allergic asthma and food allergy. Mice were tolerized with Ag-SP before or after initiation of OVA/alum-induced allergic airway inflammation or peanut-induced food allergy. The effects on disease pathology and Th2-directed cytokine and Ab responses were studied. Ag-SP tolerance prevented disease development in both models and safely tolerized T cell responses in an Ag-specific manner in presensitized animals. Prophylactically, Ag-SP efficiently decreased local and systemic Th2 responses, eosinophilia, and Ag-specific IgE. Interestingly, Ag-SP induced Th2 tolerance was found to be partially dependent on the function of CD25(+) regulatory T cells in the food allergy model, but was regulatory T cell independent in the model of allergic airway inflammation. We demonstrate that Ag-SP tolerance can be rapidly, safely, and efficiently induced in murine models of allergic disease, highlighting a potential new Ag-specific tolerance immunotherapy for Th2 associated allergic diseases. PMID- 21976776 TI - Platypus TCRMU provides insight into the origins and evolution of a uniquely mammalian TCR locus. AB - TCRMU is an unconventional TCR that was first discovered in marsupials and appears to be absent from placental mammals and nonmammals. In this study, we show that TCRMU is also present in the duckbill platypus, an egg-laying monotreme, consistent with TCRMU being ancient and present in the last common ancestor of all extant mammals. As in marsupials, platypus TCRMU is expressed in a form containing double V domains. These V domains more closely resemble Ab V than that of conventional TCR. Platypus TCRMU differs from its marsupial homolog by requiring two rounds of somatic DNA recombination to assemble both V exons and has a genomic organization resembling the likely ancestral form of the receptor genes. These results demonstrate that the ancestors of placental mammals would have had TCRMU but it has been lost from this lineage. PMID- 21976775 TI - Dimethyl fumarate, an immune modulator and inducer of the antioxidant response, suppresses HIV replication and macrophage-mediated neurotoxicity: a novel candidate for HIV neuroprotection. AB - Despite antiretroviral therapy (ART), HIV infection promotes cognitive dysfunction and neurodegeneration through persistent inflammation and neurotoxin release from infected and/or activated macrophages/microglia. Furthermore, inflammation and immune activation within both the CNS and periphery correlate with disease progression and morbidity in ART-treated individuals. Accordingly, drugs targeting these pathological processes in the CNS and systemic compartments are needed for effective, adjunctive therapy. Using our in vitro model of HIV mediated neurotoxicity, in which HIV-infected monocyte-derived macrophages release excitatory neurotoxins, we show that HIV infection dysregulates the macrophage antioxidant response and reduces levels of heme oxygenase-1 (HO-1). Furthermore, restoration of HO-1 expression in HIV-infected monocyte-derived macrophages reduces neurotoxin release without altering HIV replication. Given these novel observations, we have identified dimethyl fumarate (DMF), used to treat psoriasis and showing promising results in clinical trials for multiple sclerosis, as a potential neuroprotectant and HIV disease-modifying agent. DMF, an immune modulator and inducer of the antioxidant response, suppresses HIV replication and neurotoxin release. Two distinct mechanisms are proposed: inhibition of NF-kappaB nuclear translocation and signaling, which could contribute to the suppression of HIV replication, and induction of HO-1, which is associated with decreased neurotoxin release. Finally, we found that DMF attenuates CCL2-induced monocyte chemotaxis, suggesting that DMF could decrease recruitment of activated monocytes to the CNS in response to inflammatory mediators. We propose that dysregulation of the antioxidant response during HIV infection drives macrophage-mediated neurotoxicity and that DMF could serve as an adjunctive neuroprotectant and HIV disease modifier in ART-treated individuals. PMID- 21976777 TI - Prostaglandin I2promotes the development of IL-17-producing gammadelta T cells that associate with the epithelium during allergic lung inflammation. AB - gammadelta T cells rapidly produce cytokines and represent a first line of defense against microbes and other environmental insults at mucosal tissues and are thus thought to play a local immunoregulatory role. We show that allergic airway inflammation was associated with an increase in innate IL-17-producing gammadelta T (gammadelta-17) cells that expressed the alphaEbeta7 integrin and were closely associated with the airway epithelium. Importantly, PGI(2) and its receptor IP, which downregulated airway eosinophilic inflammation, promoted the emergence of these intraepithelial gammadelta-17 cells into the airways by enhancing IL-6 production by lung eosinophils and dendritic cells. Accordingly, a pronounced reduction of gammadelta-17 cells was observed in the thymus of naive mice lacking the PGI(2) receptor IP, as well as in the lungs during allergic inflammation, implying a critical role for PGI(2) in the programming of "natural" gammadelta-17 cells. Conversely, iloprost, a stable analog of PGI(2), augmented IL-17 production by gammadelta T cells but significantly reduced airway inflammation. Together, these findings suggest that PGI(2) plays a key immunoregulatory role by promoting the development of innate intraepithelial gammadelta-17 cells through an IL-6-dependent mechanism. By enhancing gammadelta 17 cell responses, stable analogs of PGI(2) may be exploited in the development of new immunotherapeutic approaches. PMID- 21976779 TI - Modification of yttrium alkoxides: beta-Ketoesterate-substituted yttrium alkoxo/hydroxo/oxo clusters. AB - Reaction of Y(5)O(OiPr)(13) ("yttrium iso-propoxide") with one molar equivalent of isopropyl acetoacetate (iprac) per Y resulted in the formation of Y(9)O(OH)(9)(OiPr)(8)(iprac)(8), a rare example of an yttrium alkoxo/hydroxo/oxo cluster. Reaction in a 1:3 molar ratio gave Y(4)(OH)(2)(iprac)(10) and Y(6)(OH)(6)(iprac)(12) instead. A fourth cluster, Y(9)O(OH)(9)(iprac)(16), structurally closely related to Y(9)O(OH)(9)(OiPr)(8)(iprac)(8), was obtained upon recrystallization of Y(4)(OH)(2)(iprac)(10) from CDCl(3). PMID- 21976780 TI - CJDATS CO-OCCURRING DISORDERS SCREENING INSTRUMENT (CODSI) FOR MENTAL DISORDERS (MD): A Validation Study. AB - Three standardized screening instruments-the Global Appraisal of Individual Needs Short Screener (GSS), the Mini-International Neuropsychiatric Interview-Modified (MINI-M), and the Mental Health Screening Form (MHSF)-were compared to two shorter instruments, the 6-item Co-Occurring Disorders Screening Instrument for Mental Disorders (CODSI-MD) and the 3-item CODSI for Severe Mental Disorders (CODSI-SMD) for use with offenders in prison substance-abuse treatment programs. Results showed that the CODSI screening instruments were comparable to the longer instruments in overall accuracy and that all of the instruments performed reasonably well. The CODSI instruments showed sufficient value to justify their use in prison substance-abuse treatment programs and to warrant validation testing in other criminal justice populations and settings. PMID- 21976781 TI - Robust detection and tracking of annotations for outdoor augmented reality browsing. AB - A common goal of outdoor augmented reality (AR) is the presentation of annotations that are registered to anchor points in the real world. We present an enhanced approach for registering and tracking such anchor points, which is suitable for current generation mobile phones and can also successfully deal with the wide variety of viewing conditions encountered in real life outdoor use. The approach is based on on-the-fly generation of panoramic images by sweeping the camera over the scene. The panoramas are then used for stable orientation tracking, while the user is performing only rotational movements. This basic approach is improved by several new techniques for the re-detection and tracking of anchor points. For the re-detection, specifically after temporal variations, we first compute a panoramic image with extended dynamic range, which can better represent varying illumination conditions. The panorama is then searched for known anchor points, while orientation tracking continues uninterrupted. We then use information from an internal orientation sensor to prime an active search scheme for the anchor points, which improves matching results. Finally, global consistency is enhanced by statistical estimation of a global rotation that minimizes the overall position error of anchor points when transforming them from the source panorama in which they were created, to the current view represented by a new panorama. Once the anchor points are redetected, we track the user's movement using a novel 3-degree-of-freedom orientation tracking approach that combines vision tracking with the absolute orientation from inertial and magnetic sensors. We tested our system using an AR campus guide as an example application and provide detailed results for our approach using an off-the-shelf smartphone. Results show that the re-detection rate is improved by a factor of 2 compared to previous work and reaches almost 90% for a wide variety of test cases while still keeping the ability to run at interactive frame rates. PMID- 21976782 TI - Major league baseball career length in the twentieth century. AB - Although baseball is considered "the" American pastime, little is known about the career prospects of the individuals who play the game. This study fills that void by examining the careers of baseball players over the last century. Between 1902 and 1993, 5,989 position players started their careers and played 33,272 person years of major league baseball. A rookie position player can expect to play 5.6 years; one in five position players will have only a single-year career, and at every point of a player's career, the chance of exiting is at least 11%. Position players who start younger and begin their career in more recent decades all have longer and more stable careers; nevertheless, baseball careers are not compressed versions of normal careers, but are substantially skewed toward early exit. PMID- 21976783 TI - Lateralisation of language and emotion in schizotypal personality: Evidence from dichotic listening. AB - Striking disturbances have been reported in language and emotional prosody processing by patients diagnosed with schizophrenia. In view of this and of research suggesting that schizotypal personality traits can also be expressed sub clinically, the present study aimed to discover whether similar disturbances would be reflected in cognitive laterality patterns when symptoms of schizotypy are present yet at a non-clinical level. A dichotic listening task was used to examine the sensitivity and speed with which 132 right-handed participants (85 females and 47 males, mean age = 32.44, SD = 12.29) detected both words and emotional prosody, all of whom also completed the Schizotypal Personality Questionnaire. Findings indicated that both high (n = 64) and low (n = 68) schizotypy groups demonstrated the typical right ear advantage for the detection of words and left ear advantage for the detection of emotional prosody. Individuals with higher schizotypal personality scores also demonstrated poorer sensitivity in detecting emotional prosody. These results reveal that within the healthy population, higher levels of schizotypy are not associated with the atypical lateralisation of language and emotion. Nevertheless, the existence of these symptoms does signal the presence of shared characteristics with the clinical sphere, namely poorer emotion recognition performance. PMID- 21976784 TI - Group Interventions were not Effective for Female Turkish Migrants with Recurrent Depression - Recommendations from a Randomized Controlled Study. AB - We tested group interventions for women with a Turkish migration background living in Austria and suffering from recurrent depression. N = 66 participants were randomized to: (1) Self-Help Groups (SHG), (2) Cognitive Behavior Therapy (CBT) Groups, and (3) a Wait-List (WL) Control condition. Neither SHG nor CBT were superior to WL. On an individual basis, about one third of the participants showed significant improvements with respect to symptoms of depression. Younger women, women with a longer duration of stay in Austria and those who had encountered a higher number of traumatic experiences, showed increased improvement of depressive symptoms. The results suggest that individual treatment by ethnic, female psychotherapists should be preferred to group interventions. PMID- 21976785 TI - Sustainable energy development in Austria until 2020: Insights from applying the integrated model "e3.at" AB - This paper reports on the Austrian research project "Renewable energy in Austria: Modeling possible development trends until 2020". The project investigated possible economic and ecological effects of a substantially increased use of renewable energy sources in Austria. Together with stakeholders and experts, three different scenarios were defined, specifying possible development trends for renewable energy in Austria. The scenarios were simulated for the period 2006 2020, using the integrated environment-energy-economy model "e3.at". The modeling results indicate that increasing the share of renewable energy sources in total energy use is an important but insufficient step towards achieving a sustainable energy system in Austria. A substantial increase in energy efficiency and a reduction of residential energy consumption also form important cornerstones of a sustainable energy policy. PMID- 21976778 TI - Early steps in steroidogenesis: intracellular cholesterol trafficking. AB - Steroid hormones are made from cholesterol, primarily derived from lipoproteins that enter cells via receptor-mediated endocytosis. In endo-lysosomes, cholesterol is released from cholesterol esters by lysosomal acid lipase (LAL; disordered in Wolman disease) and exported via Niemann-Pick type C (NPC) proteins (disordered in NPC disease). These diseases are characterized by accumulated cholesterol and cholesterol esters in most cell types. Mechanisms for trans cytoplasmic cholesterol transport, membrane insertion, and retrieval from membranes are less clear. Cholesterol esters and "free" cholesterol are enzymatically interconverted in lipid droplets. Cholesterol transport to the cholesterol-poor outer mitochondrial membrane (OMM) appears to involve cholesterol transport proteins. Cytochrome P450scc (CYP11A1) then initiates steroidogenesis by converting cholesterol to pregnenolone on the inner mitochondrial membrane (IMM). Acute steroidogenic responses are regulated by cholesterol delivery from OMM to IMM, triggered by the steroidogenic acute regulatory protein (StAR). Chronic steroidogenic capacity is determined by CYP11A1 gene transcription. StAR mutations cause congenital lipoid adrenal hyperplasia, with absent steroidogenesis, potentially lethal salt loss, and 46,XY sex reversal. StAR mutations initially destroy most, but not all steroidogenesis; low levels of StAR-independent steroidogenesis are lost later due to cellular damage, explaining the clinical findings. Rare P450scc mutations cause a similar syndrome. This review addresses these early steps in steroid biosynthesis. PMID- 21976786 TI - Semiparametric inference of proportional odds model based on randomly truncated data. AB - This paper studies the estimation in the proportional odds model based on randomly truncated data. The proposed estimators for the regression coefficients include a class of minimum distance estimators defined through weighted empirical odds function. We have investigated the asymptotic properties like the consistency and the limiting distribution of the proposed estimators under mild conditions. The finite sample properties were investigated through simulation study making comparison of some of the estimators in the class. We conclude with an illustration of our proposed method to a well-known AIDS data. PMID- 21976787 TI - Effect of oxide particles on the stabilization and final microstructure in aluminium. AB - Bulk aluminium samples containing alumina particles have been produced by different severe plastic deformation methods. Aluminium foils with different initial foil thicknesses were cold rolled to different amounts of strain and aluminium powders were consolidated and deformed by high pressure torsion (HPT). During processing, alumina particles from the foil or particle surface are easily incorporated and dispersed in the bulk material. The influence of these alumina particles on the developing microstructures and the mechanical properties has been studied. PMID- 21976789 TI - Sexual and reproductive health services: priorities for South and East Asia. PMID- 21976790 TI - India's Progress Toward Achieving the Millennium Development Goals. PMID- 21976791 TI - Are we Really Producing Public Health Experts in India? Need for a Paradigm Shift in Postgraduate Teaching in Community Medicine. PMID- 21976788 TI - Dendritic cells in human atherosclerosis: from circulation to atherosclerotic plaques. AB - BACKGROUND: Atherosclerosis is a chronic inflammatory disease with atherosclerotic plaques containing inflammatory infiltrates predominantly consisting of monocytes/macrophages and activated T cells. More recent is the implication of dendritic cells (DCs) in the disease. Since DCs were demonstrated in human arteries in 1995, numerous studies in humans suggest a role for these professional antigen-presenting cells in atherosclerosis. AIM: This paper focuses on the observations made in blood and arteries of patients with atherosclerosis. In principal, flow cytometric analyses show that circulating myeloid (m) and plasmacytoid (p) DCs are diminished in coronary artery disease, while immunohistochemical studies describe increased intimal DC counts with evolving plaque stages. Moreover, mDCs and pDCs appear to behave differently in atherosclerosis. Yet, the origin of plaque DCs and their relationship with blood DCs are unknown. Therefore, several explanations for the observed changes are postulated. In addition, the technical challenges and discrepancies in the research field are discussed. FUTURE: Future studies in humans, in combination with experimental animal studies will unravel mechanisms leading to altered blood and plaque DCs in atherosclerosis. As DCs are crucial for inducing but also dampening immune responses, understanding their life cycle, trafficking and function in atherosclerosis will determine potential use of DCs in antiatherogenic therapies. PMID- 21976792 TI - Air nicotine monitoring for second hand smoke exposure in public places in India. AB - BACKGROUND: Air nicotine monitoring is an established method of measuring exposure to second hand smoke (SHS). Not much research has been done in India to measure air nicotine for the purpose of studying exposure to SHS. It is a risk factor and many diseases are known to occur among non smokers if they are exposed to second hand smoke. OBJECTIVE: To conduct monitoring of air nicotine for second hand smoke exposure in public places across major cities in India. MATERIALS AND METHODS: A cross sectional survey was conducted across four cities across the country, using passive air monitoring. The buildings included hospitals, secondary schools, Governmental offices, bars and restaurants. The buildings were selected through convenience sampling method keeping in view specific sentinel locations of interest. RESULT: The presence of air nicotine was recorded in most of the buildings under the study, which included government buildings, hospitals, schools, restaurants and entertainment venues (bars) in all four cities under the study. The highest median levels of air nicotine were found in entertainment venues and restaurants in cities. CONCLUSION: The presence of air nicotine in indoor public places indicates weak implementation of existing smoke free law in India. The findings of this study provide a baseline characterization of exposure to SHS in public places in India, which could be used to promote clean indoor air policies and programs and monitor and evaluate the progress and future smoke-free initiatives in India. PMID- 21976793 TI - Preparedness for tobacco control among postgraduate residents of a medical college in bangalore. AB - BACKGROUND: Tobacco use is a major cause of avoidable mortality. Postgraduate doctors in training are an important group of physicians likely to influence patients' tobacco use/cessation. OBJECTIVE: To assess preparedness for tobacco control among clinical postgraduate residents of a medical college in southern India. MATERIALS AND METHODS: A cross-sectional study was undertaken among all clinical postgraduate residents enrolled in St. John's Medical College, Bangalore, to assess knowledge, attitude, and practice regarding tobacco cessation in their patients. A self-administered, anonymous questionnaire was used. Simple descriptive analysis was undertaken. RESULTS: The overall response rate was 66% (76/116). Mean (S.D.) knowledge score on tobacco use prevalence and disease burden was 6.2 (2.0) out of 10. About 25% of them were not aware of nicotine replacement therapy as a treatment option for tobacco cessation. Nearly two thirds of them expected their patients to ask for assistance with quitting and nearly half were sceptical about patients' ability to quit. While 80% of them enquired routinely about tobacco use in their patients, only 50% offered advice on quitting and less than a third assessed readiness to quit or offered assistance with quitting in their patients. CONCLUSION: Our study revealed suboptimal levels of knowledge and tobacco cessation practice among postgraduate residents. Attitudes toward tobacco cessation by their patients was however generally positive and there was substantial interest in further training in tobacco control. Reorienting postgraduate medical education to include tobacco control interventions would enable future physicians to be better equipped to deal with nicotine addiction. PMID- 21976794 TI - Mass measles rubella immunization campaign: bhutan experience. AB - BACKGROUND: Bhutan has attained universal child immunization since 1991. Since then, immunization coverage is maintained at high level through routine immunization, periodic National Immunization Days, and mop up campaigns. Despite high immunization coverage, every year, significant numbers of clinically suspected measles cases were reported. OBJECTIVE: To assess the cause of continuing high "suspected measles cases" and take appropriate public health measures. MATERIALS AND METHODS: Febrile rash outbreaks occurred in several districts in 2003. These episodes were investigated. Simultaneously, a retrospective data search revealed evidence of congenital rubella syndrome (CRS) in the country. RESULTS: Thirty five percent of the tested samples were positive for rubella but none for measles. There were evidences of the presence of CRS. This was discussed in the annual health conference 2004, amongst health policy makers and district heads who recommended that a possibility of inclusion of rubella as an antigen be looked into. A nationwide measles and rubella immunization campaign was conducted in 2006 followed by introduction of rubella vaccine in the immunization schedule. CONCLUSION: Febrile rash can be caused by a host of viral infections. Following universal measles immunization, it is pertinent that febrile rash be looked in the light of rubella infections. Following the introduction of rubella vaccination in the national immunization schedule, there has been significant reduction of febrile rash episodes, cases of rubella, and congenital rubella syndrome. PMID- 21976795 TI - Profile of Home-based Caregivers of Bedridden Patients in North India. AB - BACKGROUND: Caregiving to bedridden patients in India is set to become a major problem in future. OBJECTIVE: To ascertain the profile of caregivers for the adult bedridden patients in Chandigarh, India. MATERIALS AND METHODS: This cross sectional study was conducted on 100 purposively selected bedridden people. The Katz Index of the activities of daily living was used to ascertain their degree of disability. Patients and families were interviewed about the patterns of care provision. RESULTS: The mean age of subjects was 69 years. A majority (68%) of them lived in joint families. All of them required assistance in bathing, dressing, toileting, and transfer. In 54% of the cases someone was hired to look after the subjects. A majority of the caregivers (82%) were family members. All caregivers were untrained. In 35% of the cases unqualified practitioners were consulted, while in 59% of the cases government hospitals were consulted. Most patients (78) were given medicines on time. Complications like urinary tract infection (39%) and pressure ulcers (54%) were reported; 57% of the patients reported satisfaction with the care provided. CONCLUSION: The main source of caregivers for the bedridden was the family. Bedridden people had high rates of medical complications. There is a need for formal training for the caregivers. PMID- 21976796 TI - Pregnancy outcome of women with gestational diabetes in a tertiary level hospital of north India. AB - BACKGROUND: Women with gestational diabetes mellitus (GDM) pose an important public health problem because diabetes not only affects the maternal and fetal outcome, but these women and their fetuses are also at an increased risk of developing diabetes and related complications later in their life. OBJECTIVES: The study was conducted to determine the maternal and fetal outcomes of 50 diabetic vs 50 normoglycemic pregnancies. MATERIALS AND METHODS: This was a retrospective analytical record-based study conducted in a tertiary level hospital. Detailed information regarding maternal, fetal, and labor outcome parameters was recorded in a prestructured proforma and compared in normoglycemic and diabetic pregnancies. RESULTS: Patients with obesity, history of diabetes in the family, spontaneous abortions, and gestational diabetes in previous pregnancies had a greater incidence of GDM in current pregnancy (P<0.05 for all). Hypertension, polyhydramnios, macrosomia, fetopelvic disproportion, and cesarean sections were more (P<0.001) among diabetic pregnancies. Congenital anomalies, polycythemia, hypocalcemia, and hyperbilirubinemia were also observed to be more (P<0.05) in neonates born to diabetics, suggesting an adverse effect of hyperglycemia in utero. CONCLUSION: Diabetes during pregnancy is associated with higher maternal and fetal morbidity. Therefore, early screening, detection, close monitoring, and intervention is essential to reduce maternal and fetal short- and long-term adverse effects, especially in high-risk groups. Pregnancy provides an opportunity to the clinician to control the disease process and inculcate healthy lifestyle practices in these patients. PMID- 21976797 TI - Prevalence of chikungunya in urban field practice area of a private medical college, chennai. AB - BACKGROUND: The outbreak of Chikungunya in India started during December 2005 with more than 11,00,000 cases. Many cases with symptoms suggestive of Chikungunya reported to our urban health-training centre. Hence this study was done to estimate the prevalence of Chikungunya, to study the common treatment seeking behavior, control measures and the sequalae of Chikungunya by follow-up. MATERIALS AND METHODS: This cross-sectional study was done in Anagaputhur an urban field practice area of our college. The study was done on a sample selected by systematic random sampling. Any person with fever and joint pain, with an onset from 1 August 2006 to 31 August 2006, were enrolled as cases. The cases were followed up after three months. RESULTS: Chikungunya prevalence in the community was 22.3%; 52% of them were females and 56% of cases were in the 15-44 years age group. Median duration of acute phase was three days. Ninety-one percent of them had multiple joints' involvement. Seventy-eight percent sought treatment from the private sector. Sixty-seven percent reported artificial collections of water around their household and 44% complained of mosquito problems during the day. Eighty-eight percent used mosquito repellents for personal protection. On follow-up 95% of them had residual joint pain, 43% had residual joint swelling and 11% had disabilities with median duration of 30 days. CONCLUSIONS: Prevalence of Chikungunya was 22.3%, predominantly affecting the age group of 15-44 years and females. The private sector was commonly sought for treatment. Entomological survey indicated Aedes breeding. Eleven percent had disabilities due to the sequelae. PMID- 21976798 TI - Tobacco Chewing and Associated Factors Among Youth of Western Nepal: A Cross sectional Study. AB - BACKGROUND: Smokeless tobacco is found to be as addictive and harmful as smoking but have not been explored into, especially among youth. OBJECTIVES: This study was conducted to find the prevalence of tobacco chewing among college students in Nepal and the factors that have influence over their use. STUDY DESIGN: A cross sectional study with a self-administered questionnaire. MATERIALS AND METHODS: Five colleges of different streams in Pokhara city were selected for the study. A total of 816 students participated. The study was conducted during the period of May 2006-February 2007, using a semi-structured, self-administered questionnaire. RESULTS: Overall prevalence of ever tobacco chewing was 21.3% (males 30.2% and females 10.9%) among the youth with average age of initiation 15.7 years. Pan masala and gutka were used by 63.6% and frequency of use varied widely and only 5.7% said they were daily users. Reasons cited for chewing were most commonly 'just like it' or 'friends chew'. Multiple logistic regression analysis showed age, ever smoking status, being ever alcoholic, and having friends or family members who chewed were significantly associated with students' tobacco chewing. Almost one-tenth of the students believed they were addicted to chewing tobacco and 42.5% of them had tried to quit the habit. CONCLUSION: The study shows a high prevalence of tobacco chewing by Nepali youth. Important factors that influenced the habit were having chewer friends, their own smoking and alcohol status and having family members who chewed. It is pertinent to consider these when formulating cessation and prevention programs. PMID- 21976799 TI - Oral Cancer Screening at Workplace in India-One-year Follow-up. AB - BACKGROUND: Oral cancer remains the commonest form of cancer and cancer-related deaths among Indian males due to popularity of avoidable risk factors such as tobacco and alcohol use. A workplace oral cancer screening and tobacco cessation study was commenced on World No Tobacco Day 2007 at a chemical industry in rural Maharashtra. AIMS: The objectives were to screen the employees for oral neoplasia and to correlate it with their tobacco consumption pattern. In addition, the objective was to provide tobacco cessation services at the workplace. MATERIALS AND METHODS: This is an interventional cohort study among 104 employees of a chemical industrial unit in rural Maharashtra. Naked eye examination of the oral cavity was performed for all employees by a doctor irrespective of the tobacco habits at the beginning and at the end of 1 year. In between, the tobacco users were regularly examined during each follow-up. STATISTICAL ANALYSIS USED: Through personal interviews of the participants, data were manually recorded and were transferred to electronic data base. Data analysis was conducted in STATATM 8.2 on intention to treat basis. RESULTS AND CONCLUSIONS: Among the 104 employees, 50 (48.08%) were current tobacco users at the beginning of the program. Oral precancers were seen exclusively among 20 (40%) tobacco users. After 1 year of workplace tobacco cessation intervention, 80% of oral precancers regressed. This shows that screening of the oral cavity at the workplace is effective when combined with tobacco cessation. PMID- 21976800 TI - Early Infant Diagnosis: A New Tool of HIV Diagnosis in Children. AB - BACKGROUND: Standard assay has limited utility in diagnosing HIV reactivity among infants till the age of 18 months by which time, many HIV-infected infants expire. The test for diagnosing infant and children below 18 months is DNA polymerase chain reaction (DNAPCR) either by dried blood spot (DBS) or whole blood sample (WBS). Early infant diagnosis (EID) project is implemented in 18 districts of Gujarat through 33 PPTCT centers from 1st April 2010. Present analysis is done to evaluate factors curbing mother to child HIV transmission. MATERIALS AND METHODS: Study included all children (< 18 months) who are born to HIV-positive mothers or referred children with signs/ symptoms of HIV with unknown parent status or children already on anti-retroviral therapy whose status could not be confirmed by antibody tests. Data was compiled and analyzed according to the infant's age at testing, type of feeding, history of Anti retero viral (ARV) prophylaxis, and type of delivery. Data compiled between April and August 2010 was used for the analysis. RESULTS: Cohort of 326 infants was followed up, fewer infants (14/270) who received ARV prophylaxis tested positive than those who did not (23/56). Transmission was more in normal delivery (29/252) than cesarean (8/74). Low transmission rate was seen in replacement feeding (13/208) than breast/mixed feeding (24/94). Out of 37 samples found positive by the DBS, 17 were sent for WBS and all were found to be positive. CONCLUSION: DBS test results were found as accurate as WBS. So DBS (less cumbersome and cost effective) can be used in future exclusively. Nevirapine administration at birth as mother baby pair showed 36% decrease in MTCT. PMID- 21976801 TI - Knowledge, Attitude, and Practices about Biomedical Waste Management among Healthcare Personnel: A Cross-sectional Study. AB - BACKGROUND: The waste produced in the course of healthcare activities carries a higher potential for infection and injury than any other type of waste. Inadequate and inappropriate knowledge of handling of healthcare waste may have serious health consequences and a significant impact on the environment as well. OBJECTIVE: The objective was to assess knowledge, attitude, and practices of doctors, nurses, laboratory technicians, and sanitary staff regarding biomedical waste management. MATERIALS AND METHODS: This was a cross-sectional study. SETTING: The study was conducted among hospitals (bed capacity >100) of Allahabad city. PARTICIPANTS: Medical personnel included were doctors (75), nurses (60), laboratory technicians (78), and sanitary staff (70). RESULTS: Doctors, nurses, and laboratory technicians have better knowledge than sanitary staff regarding biomedical waste management. Knowledge regarding the color coding and waste segregation at source was found to be better among nurses and laboratory staff as compared to doctors. Regarding practices related to biomedical waste management, sanitary staff were ignorant on all the counts. However, injury reporting was low across all the groups of health professionals. CONCLUSION: The importance of training regarding biomedical waste management needs emphasis; lack of proper and complete knowledge about biomedical waste management impacts practices of appropriate waste disposal. PMID- 21976802 TI - Comparative Analysis of RNTCP Indicators in a Rural and an Urban Tuberculosis Unit of Burdwan District in West Bengal. AB - BACKGROUND: Data pertaining to managerial indicators of RNTCP are rare. The present study was done to analyze the RNTCP indicators in one rural and one urban tuberculosis unit in Burdwan, West Bengal, and find out any influencing factor. MATERIALS AND METHODS: A comparative record analysis for the year 2007 was undertaken RESULTS: The study revealed significantly more urban adolescents (P<0.001) were treated. In both areas, the proportion of NSN cases and smear positive retreatment cases among total smear positives were less than expected, while more NSP cases were registered. Significantly lesser retreatment cases (13.33%) were registered in the rural area. Smear negative and EP cases of all the patients in Cat I were significantly less in the rural area. Outcomes like cured, treatment completed, default, and death were similar approaching the RNTCP norm. But sputum conversion (78.02%) and failure rate (4.93%) were worse than the RNTCP norm in the urban area and varied significantly between two areas. The outcomes like cured, treatment completed, and default differed significantly with age in the areas. The outcome of TAD cases was different, but the outcomes of NSN, EP, and other retreatment cases were similar in two areas. Age at treatment onset was found to be the only factor associated with default. CONCLUSION: Managerial indicators may reveal something different despite common indicators showing acceptable results. PMID- 21976803 TI - Neonatal morbidity and mortality in tribal and rural communities in central India. AB - BACKGROUND AND OBJECTIVES: Little is known about the natural history of neonates born in the rural and tribal areas in India. The Neonatal Disease Surveillance Study (NDSS) measures the incidence of high-priority neonatal diseases, neonatal health events and associated risk factors to plan appropriate and effective actions. MATERIALS AND METHODS: The NDSS is being conducted in Ramtek Revenue Block, Nagpur district, Maharashtra state, given its considerably high level of neonatal mortality. All households from five selected primary health centers were screened. Both active and passive surveillance systems were used for systematic collection of mother's health during pregnancy and of baby's health from birth to 4 months after birth. First-year results from November 2006 to October 2007 are presented. RESULTS: Pregnancy outcomes were available for 1,136 women, with an overall neonatal mortality of 73 per 1,000 live births. The pregnancy outcomes varied by gestational age of the baby; miscarriages and abortions were higher in tribal than in non-tribal women, and tribal women had higher rates of low-birth weight (LBW) neonates than non-tribal women. The main cause of neonatal mortality was LBW, followed by sepsis and respiratory illness. The mortality of non-tribal babies was most strongly associated with pre term. For tribal babies, mortality was also associated with maternal morbidity and delay in the initiation of breastfeeding. INTERPRETATION AND CONCLUSIONS: The NDSS provides valuable information on the potentially modifiable factors associated with increased likelihood of neonatal mortality and morbidity. The Neonatal Health Research Initiative is now developing community-based interventions to reduce the high rate of neonatal mortality and morbidity in the rural areas of India. PMID- 21976804 TI - Age and Gender Disparities in Evidence-based Treatment for Coronary Artery Disease in the Community: A Cross-sectional Study. PMID- 21976805 TI - Filariasis presented as a spermatic cord nodule in a nonendemic hilly state of uttarakhand: a case report of second case in the region. PMID- 21976806 TI - Pleural effusion and ultrasonography in dengue Fever. PMID- 21976807 TI - Persistence of diphtheria in India. PMID- 21976808 TI - Emergence of Vibrio cholerae Serotype Hikojima in Northern Tamil Nadu. PMID- 21976809 TI - Health disparities: old wine in a new bottle. PMID- 21976810 TI - Where and how breastfeeding promotion initiatives should focus its attention? PMID- 21976811 TI - Mechanisms pertaining to arsenic toxicity. AB - Arsenic is an environmental pollutant and its contamination in the drinking water is considered as a serious worldwide environmental health threat. The chronic arsenic exposure is a cause of immense health distress as it accounts for the increased risk of various disorders such as cardiovascular abnormalities, diabetes mellitus, neurotoxicity, and nephrotoxicity. In addition, the exposure to arsenic has been suggested to affect the liver function and to induce hepatotoxicity. Moreover, few studies demonstrated the induction of carcinogenicity especially cancer of the skin, bladder, and lungs after the chronic exposure to arsenic. The present review addresses diverse mechanisms involved in the pathogenesis of arsenic-induced toxicity and end-organ damage. PMID- 21976812 TI - Ameliorative effects of tinospora cordifolia root extract on histopathological and biochemical changes induced by aflatoxin-b(1) in mice kidney. AB - The present study was planned to investigate the ability of the Tinospora cordifolia to scavenge free radicals generated during aflatoxicosis. A total no. of 48 male Swiss albino mice (30 +/- 5 g) were exposed to Aflatoxin B(1)(AFB(1)) (2 MUg/30 g b.wt, orally) either individually or in combination with T. cordifolia (50, 100, 200 mg/kg, orally) once daily for 25 days. AFB(1) exposure led to significant rise in thiobarbituric acid reactive substances (TBARS) and fall in superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), ascorbic acid, and protein content. T. cordifolia was found to show protective effect by lowering down the content of TBARS and enhancing the GSH, ascorbic acid, protein, and the activities of antioxidant enzymes viz., SOD, CAT, glutathione peroxidase, GST, and GR in kidney. Histopathological analysis of kidney samples also confirmed the protective values and antioxidant activity of ethanolic extract of herb. T. cordifolia showed protection against aflatoxin induced nephrotoxicity due to the presence of alkaloids such as a choline, tinosporin, isocolumbin, palmatine, tetrahydropalmatine, and magnoflorine. PMID- 21976813 TI - Chronic fluoride toxicity and myocardial damage: antioxidant offered protection in second generation rats. AB - This experiment was designed to investigate the extent of peroxidative changes and histological alterations in the myocardium of rats exposed to high fluoride for two generations, in addition to ameliorative role of selenium and vitamin E on the above indices. Adult albino Wistar rats were given fluoride through drinking water (200 ppm F) and maintained subsequently for two generations, while they were exposed to fluoride throughout the experiment. Fluoride treatment significantly increased the lipid peroxidation and decreased the activity of antioxidant enzymes, viz., catalase, superoxide dismutase, and glutathione level in auricle and ventricle regions of the heart. Decreased feed and water consumption, organ somatic index and marginal drop in body growth rate were observed. Decreased antioxidant enzymes and increased malondialdehyde levels might be related to oxidative damage that occurs variably in the myocardium of rats. Biochemical changes were supported by the histological observations, which also revealed that chronic exposure to fluoride causes damage to the myocardium. Results of this study can be taken as an index of cardio-toxicity in rats exposed to water fluoridation. Further, oral supplementation of selenium and vitamin E not only inhibited oxidative stress but also enhanced the activities of antioxidant enzymes. Administration of antioxidants during fluoride exposure significantly overcame cardiac fluoride toxicity and therefore may be a therapeutic strategy for fluorotic victims. PMID- 21976814 TI - Effect of Trans-resveratrol on Rotenone-induced Cytotoxicity in Human Breast Adenocarcinoma Cells. AB - Rotenone, a botanical insecticide is known to cause apoptosis in various cell types. Trans-resveratrol, a natural phytophenol present in red grapes and wine, is also well documented for its antioxidant, anti-inflammatory, anti-mutagenic, and anticarcinogenic activities. Therefore, the present investigations were carried out to assess the protective effect of trans-resveratrol against rotenone induced cell death in human breast adenocarcinoma (MCF-7) cells. MCF-7 cells were exposed with various concentrations of rotenone for 24 h, and the loss in percent cell viability was evaluated by MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide] and neutral red uptake (NRU) assays. A significant decrease in percent cell viability in MCF-7 cells was observed at 50 MUM and above concentrations of rotenone, as compared to untreated control. Furthermore, various concentrations (5, 10, and 25 MUM) of trans-resveratrol were used to see its protective role on cell viability in rotenone-induced cell death in MCF-7 cells. Pre- or post- treatment of trans-resveratrol for 24 h was given to the cells. The data exhibited a significant dose dependent increase in the percent cell viability under pre- and post-treatment conditions. However, post-treatment of trans-resveratrol for 24 h after rotenone exposure to the cells was relatively less effective. Overall, the results suggest that trans-resveratrol significantly protects MCF-7 cells from rotenone-induced cell death. This model can be used as an effective and economical alternative to animal models for screening the antioxidant activity of a variety of natural compounds/drugs. PMID- 21976815 TI - Identification of limiting factors for the optimum growth of fusarium oxysporum in liquid medium. AB - Fusarium oxysporum is a highly ubiquitous species that infects a wide range of hosts causing various diseases such as vascular wilts, yellows, rots, and damping off. Despite the immense economic significance of this phytopathogen, few workers have reported growth studies in this genus in submerged culture. In the present study, several parameters such as change in media pH, biomass, pattern of substrate utilization, viability of the fungal cells, and protein content were observed over a period of time. The fungal biomass increased at a slow rate for the initial 48 h and thereafter increased at an exponential rate. However, after about 8 days the rapid growth stabilized and the trend became more toward stationary phase. The concentration of glucose in the liquid media decreased rapidly up to the initial 4 days, followed by a slow decrease. The pH of the medium gradually decreased as the fungal growth progressed, the reduction being more pronounced in the initial 48 h. This study would be of immense importance for utilization of F. oxysporum for diverse applications because we can predict the growth pattern in the fungus and modulate its growth for human benefit. PMID- 21976816 TI - Serum creatine phosphokinase: a probable marker of severity in organophosphorus poisoning. AB - Organophosphorus (OP), the commonest agent for poisoning in India due to its easy availability, acts by inhibiting acetylcholinesterase at muscarinic and nicotinic receptors. Erythrocyte cholinesterase (EchE) and plasma cholinesterase (PchE) are reduced in OP poisoning, but their estimation is costly and not regularly performed. There are emerging options for new cheaper biochemical markers in relation to OP poisoning. Serum level of creatine phosphokinase (CPK) is often found to be elevated in OP poisoning. This study was conducted to see if CPK may be used as an alternative of cholinesterase levels in blood to assess the severity of OP poisoning. This was a prospective and observational study. Sixty three patients of OP poisoning without any prior treatment, presenting within 6 hours, were selected and their clinical severity was categorized according to Peradeniya organophosphorus poisoning (POP) scale. Level of serum CPK, blood EchE and pH were measured following admission, and total dose of atropine (mg) until the final clinical outcome (complete recovery or death) was calculated. Student's t-test and Pearson's correlation coefficient was used for the assessment of statistical significance. According to POP scale, clinical severity was mild (score 0-3) in 17 (27%), moderate (score 4-7) in 32 (50.8%) and severe (score 8 11) in 14 (22.2%) patients. Serum CPK, EchE level, blood pH and total atropine dose strongly correlated with clinical severity. Our study recommends serum CPK as an alternative marker. PMID- 21976817 TI - Hepatoprotective Effect of Curcumin on Lindane-induced Oxidative Stress in Male Wistar Rats. AB - Lindane, an organochlorine pesticide, is recognized as a major public health concern because of its potential toxic effects on human health. Its persistence in the body fluids may lead to continuous blood circulation, liver exposure and hepatotoxicity. The present study was undertaken to evaluate the possible protective role of curcumin on lindane-induced hepatotoxicity. Forty-two healthy adult male Wistar rats were divided into seven groups of six rats each. Group I was given dimethylsulfoxide. A single dose of lindane (60 mg/kg bw) was given to group II. Lindane (30 mg/kg bw) was given daily to group III for 14 days. Treatment with curcumin (100 and 200 mg/kg) was given to groups IV and V before (pretreatment) and to groups VI and VII after (post-treatment) 14 days exposure of lindane. Oxidative stress parameters and antioxidative enzymes were investigated in the liver of exposed and treated rats. A significant increase in lipid peroxidation, and decrease in glutathione level, Superoxide dismutase catalase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase and NADPH quinine reductase activities was observed in liver of rats exposed to lindane. Curcumin (Pre- and post-treatment) nearly normalized all these parameters. Histological alterations were also observed in the liver tissue after lindane exposure. Treatment with curcumin significantly prevented the lindane-induced histological alterations. In conclusion, curcumin has protective effect over lindane-induced oxidative damage in rat liver. PMID- 21976818 TI - Ameliorative effect of ocimum sanctum on meloxicam induced toxicity in wistar rats. AB - An ameliorating effect of Ocimum sanctum on the toxic effect of meloxicam, a new non-steroidal anti-inflammatory drug was studied by evaluating haemato biochemical parameters, oxidative stress, gross and histopathological changes in various organs of Wistar rats. A total of thirty-six male rats were divided in six experimental groups each comprising of six rats and numbered from G(1) to G(6). Meloxicam toxicity was induced by oral feeding of meloxicam at 1.2 mg/kg and 2.4 mg/kg body weight in G(2) and G(3) respectively for 28 days. Group G(4) and G(5) were fed with 1.2-mg/kg body weight and 2.4-mg/kg body weight of meloxicam along with 200 mg/kg body weight of aqueous extract of Ocimum sanctum. Group G(1) serve as control while group G(6) was kept as treatment control and fed only aqueous extract of Ocimum sanctum at 200 mg/kg body weight. Clinical finding showed mild diarrhea from 23(rd) day onwards in-group treated with 2.4 mg/kg body of meloxicam. Significant reduction of hemoglobin and packed cell volume (PCV) was observed in both the group treated with 1.2 mg/kg and 2.4-mg/kg body wt. of meloxicam. Ocimum sanctum could restore the hemoglobin and PCV value in-group treated with meloxicam at low dose level. Serum alkaline phosphatase, serum glutamic pyruvic transaminase, Serum glutamic oxaloacetic transaminase and total bilirubin were found elevated in meloxicam treated groups and indicated hepatotoxic activity of meloxicam. Ocimum sanctum could reduce hepatotoxic activity of meloxicam in group G4 receiving meloxicam at lower dose rate along with Ocimum sanctum failed to regulate creatinine level in meloxicam treated groups. In meloxicam toxicity elevated Lipid peroxidation values was noticed in liver and kidneys, while superoxide dismutase and glutathione did not revealed any change. Stomach and intestine revealed hemorrhagic gastroenteritis and ulcers. Perivascular necrosis with infiltration with inflammatory cells was evident in liver. Interstitial nephritis, myocardial necrosis and spongiform encephalopathy were important lesions. The Ocimum sanctum could only counteract the toxic effect of meloxicam in liver and gastrointestinal tract. PMID- 21976819 TI - Chronic Arsenicosis of Cattle in West Bengal and It's Possible Mitigation by Sodium Thiosulfate. AB - Thirty milch cows having arsenic concentration in hair varying from 3 to 4 mg/kg from Dakhin Panchpota village of Nadia district, West Bengal, were divided into three equal groups where high amount of arsenic is reported to be present in soil and ground water. Groups II and III received, respectively, sodium thiosulfate 20 and 40 g to each animal for 30 days as a pilot study, whereas group I served as untreated control. Arsenic content of milk, feces, hair, and urine was estimated before and after administration of sodium thiosulfate orally at two dose level once daily for 1 month. Paddy straw, mustard oil cake, and water fed by animals were also assayed. Sodium thiosulfate significantly decreased arsenic load in milk, urine, and hair after 1 month. In milk, arsenic concentration was decreased significantly which may be beneficial for animal and human beings. PMID- 21976820 TI - Ameliorative Potential of Quercetin Against Paracetamol-induced Oxidative Stress in Mice Blood. AB - The aim of the present study was to evaluate the ameliorative potential of quercetin (QC) against paracetamol (PCM)-induced oxidative stress and biochemical alterations in mice blood. A total of 36 mice were randomly allocated into six groups, six mice in each. Group I served as healthy controls, while groups II and III were administered with N-acetylcysteine (NAC) and QC alone respectively. Group IV was administered with PCM alone. Groups V and VI were administered with PCM on day 0 followed by NAC and QC, respectively, for 6 consecutive days. On day 7(th) blood samples were obtained and subjected for the assays of oxidative stress and serum biochemical panels. Erythrocytic lipid peroxides contents of alone PCM-intoxicated mice were significantly higher, while reduced glutathione contents were found to be significantly lower in comparison with the healthy controls. The activities of antioxidant enzymes were also found to be singnificantly lower in these mice. Additionally, significantly increased activities of serum aspartate transaminase, alanine transaminase and alkaline phosphatase, as well as levels of bilirubin, urea and creatinine were revealed by these mice. Postadministration with QC remarkably alleviated the over production of MDA and improved GSH levels in PCM-intoxicated mice blood. In addition, antioxidant enzymes; glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase activities were also improved significantly in these mice. QC had also considerably ameliorated the altered biochemical parameters toward normalcy. Thus, it can be concluded that QC may constitute a remedy against PCM-induced oxidative stress and reno-hepatic injuries. PMID- 21976821 TI - A 4-week Repeated Dose Oral Toxicity and Cytotoxicity Study of Gumiganghwaltang in Crl:CD (SD) Rats. AB - Gumiganghwaltang (GGT) is a traditional oriental herbal prescription commonly used to treat colds and inflammatory diseases in Korea. This study reports the first evaluation of the oral toxicity and cytotoxicity effects of repeat doses of GGT. GGT was orally administered daily at doses of 0, 500, 1000, and 2000 mg/kg for 4 weeks. Analysis of body weight gain, mortality, clinical observations, urinalysis, blood biochemistry, hematology, organ weight, and histopathological data revealed no significant differences between the V.CONTROL and GGT-treated groups. In addition, we investigated the cytotoxicity of GGT against LNCaP, RBL 1, and BEAS-2B cell lines, and splenocytes. Based on the results, we conclude that GGT orally administered to rats is safe with no drug-related toxicity, even at the highest dose, in 4-week repeated dose studies. Thus, this concentration is considered the non-observable effect dose in rats. PMID- 21976822 TI - Cytogenetic Evaluation of the Physiological Saline Extract of a Newly Developed Dental Material "ORMO-48". AB - The ORMO-48 is a new indigenous material for dental applications, developed by the Dental Products Laboratory of our Institute. The aim of the present study was to evaluate the genotoxic effect of an indigenously developed dental material in Swiss albino mice. The genotoxic effect was evaluated by micronucleus and chromosomal aberration tests. Two grams of dental material was extracted in 10.0 ml of physiological saline at 70 degrees C for 24 h. The extract was cooled to room temperature and was used for the experiment. The experimental designed had three groups each (six mice in each group) for micronucleus and chromosomal aberration tests. The first, second, and third groups were given a single exposure of physiological saline alone (control), dental material's extract (test), and cyclophosphamide (positive control) respectively for micronucleus and chromosomal aberration tests. The result of the study indicated that, the percentage of micronucleated PCE (polychromatic erythrocytes) and NCE (normochromatic erythrocytes) induced by the dental material (extract) treated group was well comparable with control group, whereas the positive control induced significantly high (P < 0.001) micronucleated PCE when compared to control. The PCE and NCE ratio of the dental material extract treated group was similar to that of control group. The chromosomal anomalies such as chromatid/chromosomal breaks, centric rings, exchanges, dicentric, and acentric fragments were evaluated. The result showed that the anomalies of the dental material extract treated group were similar to control group, however, significant anomalies were observed in the cyclophosphamide treated group. Hence, the present study concluded that the indigenously developed biocompatible dental material, ORMO-48 is non genotoxic at our laboratory conditions. PMID- 21976823 TI - Experimental Hepatotoxicity Produced by Ethinyl estradiol. AB - Ethinyl oestradiol (EO) is the most commonly used as a component of oral contraceptive and hormonal replacement therapy (HRT) in women. However, its excessive and prolonged use may cause cytotoxicity, including cancer of many organs. Hence, the present study was performed to produce the experimental hepatotoxicity in female albino rats. EO was administered to different groups of rats, respectively @ 250, 500 and 750 MUg/kg body weight, orally, weekly for 16 and 20 weeks. One group of rats was administered with saline alone to serve as control. The rats were sacrificed after their respective experimental periods, and the livers were collected and preserved in 10% buffered formalin. Later on, the histopathological study of liver tissues was done. On the 17(th) week, the hepatic tissues showed severe congestion, focal areas of hemorrhage, extreme vacuolation of cytoplasm, distended sinusoids with dilated central veins. Degeneration and necrosis of hepatocytes as evidenced by increased cytoplasmic granularity, and dissolution of nuclear materials were seen. On the 21(st) weeks, these changes were extremely severe and quite conspicuous. Distinct fibrosis was also noticed. EO caused hepatotoxicity, the extent and severity of which were dose and time dependent, indicating that this drug at higher dose after prolonged duration (500 or 750 MUg/kg, orally, weekly for 20 weeks) may cause the standard experimental hepatotoxicity in rats. PMID- 21976824 TI - Metal analysis in citrus sinensis fruit peel and psidium guajava leaf. AB - The determination of metal traces is very important because they are involved in biological cycles and indicate high toxicity. The objective of the present study is to measure the levels of heavy metals and mineral ions in medicinally important plant species, Citrus sinensis and Psidium guajava. This study investigates the accumulation of Copper (Cu), Zinc (Zn), Cadmium (Cd), Aluminum (Al), Mercury (Hg), Arsenic (As), Selenium (Se) and inorganic minerals like Calcium (Ca) and Magnesium (Mg) in C. sinensis (sweet orange) fruit peel and P. guajava (guava) leaf, to measure the levels of heavy metal contamination. Dried powdered samples of the plants were digested using wet digestion method and elemental determination was done by atomic absorption spectrophotometer. Results are expressed as mean +/- standard deviation and analysed by student's 't' test. Values are considered significant at P < 0.05. The results were compared with suitable safety standards and the levels of Cu, Zn, Cd, Mg and Ca in C. sinensis fruit peel and P. guajava leaves were within the acceptable limits for human consumption. The order of concentration of elements in both the samples showed the following trend: Mg > Ca > Al > Zn > Cu > Cd > Hg = As = Se. The content of Hg, As and Se in C. sinensis fruit peel and P. guajava leaves was significantly low and below detection limit. The content of toxic metals in tested plant samples was found to be low when compared with the limits prescribed by various authorities (World Health Organization, WHO; International Centre for Materials Research, ICMR; American Public Health Association, APHA). The content of Hg, As and Se in C. sinensis fruit peel and P. guajava leaves was not detectable and met the appropriate safety standards. In conclusion, the tested plant parts taken in the present study were found to be safe. PMID- 21976826 TI - Metal concentration in soil. PMID- 21976825 TI - Association of circulating resistin with metabolic risk factors in Indian females having metabolic syndrome. AB - Role of resistin in insulin sensitivity and metabolic syndrome (MetS) is controversial till date. Increased serum resistin levels are associated with MetS and insulin resistance. The aim of this study was to investigate the relationship between serum resistin levels with markers of the MetS in females. In a cross sectional study, a total of 170 healthy female subjects were selected for the study. Out of which 71 (age 31.59 +/- 4.88 years) were with MetS and 99 (age 31.75 +/- 6.34 years) were without MetS. Different parameters of MetS and serum resistin level were measured according to the standard protocols as given in NCEP ATP III 2001 guideline. Serum resistin levels were significantly higher in subjects with MetS when compared with subjects without MetS [13.54 +/- 4.14 ng/ml (n = 71) vs. 7.42 +/- 2.31 ng/ml (n = 99); P <= 0.001]. Resistin levels were positively associated with waist circumference, systolic and diastolic blood pressure, plasma glucose, waist/hip ratio, serum triglycerides, serum cholesterol, serum VLDL, plasma insulin, and insulin resistance, while it was negatively associated with high-density lipoprotein. This study demonstrates a positive correlation between resistin and factors of MetS except high-density lipoprotein which was found to be negatively correlated in Indian female subjects. PMID- 21976827 TI - Diagnostic dilemma in a child with tuberculous meningitis on haloperidol therapy. PMID- 21976828 TI - A little Professionalism and a lot of Originality... Please! PMID- 21976829 TI - Marching ahead!!! PMID- 21976830 TI - The peri-implant esthetics: An unforgettable entity. AB - Esthetic demands in today's world of dentistry are scaling new heights, and are driven by the zest to look beautiful. The soft tissue esthetics around implants is the foci of attention, which, if failed to meet, leads to unacceptable esthetic failure. The aim of this article is to give a brief overview of the various vital parameters influencing the esthetics governing the peri-implant area. PMID- 21976831 TI - Critical analysis of biomarkers in the current periodontal practice. AB - Periodontal disease is a chronic microbial infection that triggers inflammation mediated loss of the periodontal ligament and alveolar bone that supports the teeth. Because of the increasing prevalence and associated comorbidities, there is a need for the development of new diagnostic tests that can detect the presence of active disease, predict future disease progression, and evaluate the response to periodontal therapy, thereby improving the clinical management of periodontal patients. The diagnosis of active phases of periodontal disease and the identification of patients at risk for active disease represent challenges for clinical investigators and practitioners. Advances in diagnostic research are moving toward methods whereby the periodontal risk can be identified and quantified by objective measures using biomarkers. Patients with periodontitis may have elevated circulating levels of specific inflammatory markers that can be correlated to the severity of the disease. Advances in the use of oral fluids as possible biological samples for objective measures of the current disease state, treatment monitoring, and prognostic indicators have boosted saliva- and other oral-based fluids to the forefront of technology. Gingival crevicular fluid (GCF) is an inflammatory exudate that can be collected at the gingival margin or within the gingival crevice. This article highlights recent advances in the use of biomarker-based disease diagnostics that focus on the identification of active periodontal disease from plaque biofilms, GCF, and saliva. PMID- 21976832 TI - Biofilms: A microbial home. AB - Microbial biofilms are mainly implicated in etiopathogenesis of caries and periodontal disease. Owing to its properties, these pose great challenges. Continuous and regular disruption of these biofilms is imperative for prevention and management of oral diseases. This essay provides a detailed insight into properties, mechanisms of etiopathogenesis, detection and removal of these microbial biofilms. PMID- 21976833 TI - Periodontal vaccine: A dream or reality. AB - Recent advances in cellular and molecular biology have led to the development of new strategies for vaccines against many types of infectious diseases. It has long been recognized that individuals who recovered from a disease developed subsequent resistance to the same. In the late 18th century, Edward Jenner developed and established the principle of vaccination using the cross protection conferred by cowpox virus, which is non-pathogenic in humans. With the rapid growth of microbial genome sequencing and bioinformatics analysis tools we have the potential to examine all the genes and proteins from any human pathogen. This technique has the capability to provide us with new targets for anti-microbial drugs and vaccines. However, to realize this potential new bioinformatics and experimental approaches to select these targets from the myriad of available candidates are required. Vaccination is a process that induces specific immune resistance to a bacterial or viral infection. PMID- 21976834 TI - Propolis mouthwash: A new beginning. AB - BACKGROUND: This study was carried out to investigate the effectiveness of a propolis-containing mouthrinse in inhibition of plaque formation and improvement of gingival health. MATERIALS AND METHODS: Thirty subjects were selected and randomly assigned into three groups of ten subjects each, which received a propolis-containing mouthrinse, or a negative control (Saline) or a positive control (Chlorhexidine 0.2%). Plaque index and gingival index were assessed at baseline and at a five-day interval. RESULTS: Chlorhexidine mouthwash was found to be better than propolis and saline in inhibiting plaque formation. Propolis was found to be only marginally better than chlorhexidine in improving gingival scores. CONCLUSION: The present study suggests that propolis might be used as a natural mouthwash, an alternative to chemical mouthwashes, e.g., chlorhexidine. Further, long term trials are required for more accurate data and any conclusive evidence. PMID- 21976835 TI - Periodontal status of a given population of West Bengal: An epidemiological study. AB - BACKGROUND: This paper presents the prevalence and severity of periodontal disease in a given population of West Bengal and its relationship with their age, sex, socioeconomic status, educational background, and dietary habits. Also, the treatment needs on the basis of Community Periodontal Index of Treatment Needs (CPITN), which might be helpful for future planning of dental services. MATERIALS AND METHODS: A sample of 22,452 individuals aged 15 years and above was selected using a random cluster sampling from the population. All the subjects sampled were weighed by age, sex, community, income group, educational level, diet pattern, and habitation. The WHO CPITN was used to assess the levels of periodontal condition and treatment needs. RESULTS: Score 2 was most prevalent in all the groups. Periodontal disease is widespread in West Bengal and a positive relation appears to exist between age, sex, socio-economic status, education level, and dietary habits with periodontal status. Comprehensive oral hygiene instruction and dental prophylaxis need to be initiated. CONCLUSION: The data on periodontal conditions presented in this study are similar to data available from WHO on global oral health. These estimates are important for the future planning of dental services in the state. PMID- 21976837 TI - Gingival zenith and its role in redefining esthetics: A clinical study. AB - BACKGROUND: The purpose of this study was to quantify some clinical parameters useful as esthetic guidelines when gingival contour is modified and to compare the left and right sides of six maxillary anterior teeth. MATERIALS AND METHODS: Maxillary casts mounted on an articulator according to the axis orbital plane were photographed from 35 young adults. The angle formed between the gingival line and maxillary midline (GLA) and the distance between the gingival zenith of the lateral incisor and the gingival line were measured (LID) using a flexible protractor and digital vernier caliper, respectively. The asymmetry was evaluated using a paired t test for the left vs right measurements of GLA and LID. The descriptive statistics for GLA and LID were calculated. RESULTS: The GLA measurements of the left side (86.7 degrees +/-4.2 degrees ) were significantly greater than those of the right side (84.6 degrees +/-5.4 degrees ), and the mean absolute symmetry for GLA was 1.7 degrees +/-4.4 degrees . The mean LID measurement was 0.92?0.11. CONCLUSIONS: The gingival zenith of the canine is apical to the gingival zenith of the incisors (GLA <90 degrees ) and the gingival zenith of the lateral incisor is below or on (17%) the gingival line when head is oriented on the axis orbital plane. A directional asymmetry was shown with the right side higher than the left side. Along with the other parameters related to dental esthetics, these clinical parameters may serve as esthetic guidelines and may enable us to obtain a more predictable outcome. PMID- 21976836 TI - Evaluation of commercially available biodegradable tetracycline fiber therapy in chronic periodontitis. AB - BACKGROUND: Chronic periodontitis is an inflammatory disorder caused by dental plaque having mixed microbial flora. The different treatment modalities available to treat this disease are aimed at removal of micro-organisms from both hard and soft tissues. Systemic as well as local anti-microbial agents are helpful adjuncts in reducing microbes especially in inaccessible areas along with mechanical debridement therapy. MATERIALS AND METHODS: The study was conducted in a split mouth design. Thirty-five patients having at least two non-adjacent sites in different quadrants with periodontal pockets >=5 mm and with bleeding on probing at initial visit were selected. The selected sites were treated with both scaling and root planing plus tetracycline fibers or with scaling and root planing alone. Baseline and follow-up measurements included plaque index, gingival index, probing pocket depth, and clinical attachment level. RESULT: Both treatment modalities were affective in improving clinical parameters over three months' observation period. The combined antimicrobial and mechanical debridement therapy has shown better results as compared with scaling and root planing alone. CONCLUSION: Application of tetracycline in modified collagen matrix following scaling and root planing might be beneficial in treatment of chronic periodontitis and improving periodontal parameters for 3-month duration. PMID- 21976838 TI - To assess the effectiveness of a chlorhexidine chip in the treatment of chronic periodontitis: A clinical and radiographic study. AB - CONTEXT: Controlled local delivery of disinfecting agents has been demonstrated to be efficient in improving the outcome of periodontal therapy. AIMS: The aim of the present study was to evaluate the efficacy of a controlled-release biodegradable chlorhexidine chip (Periocol CG) when used as an adjunct to scaling and root planing in the treatment of periodontitis. SETTINGS AND DESIGN: The study was carried out as randomized controlled two-group parallel clinical trial. MATERIALS AND METHODS: Forty patients in the age group of 30-65 years suffering from mild to moderate chronic periodontitis, having pocket depth ranging between 5 and 8 mm, were selected for the study. At the screening visit, complete history taking, periodontal examination and full-mouth supragingival scaling was carried out for each patient. At the baseline visit (on the 7(th) day), all clinical parameters and radiographic parameters were recorded at selected sites and patients were randomly assigned to either the control group (group A) or the treatment group (group B). All patients in both the groups received complete subgingival scaling and root planing. Then, in group B, chlorhexidine chip (Periocol CG) was inserted at the selected site. Patients were recalled at 1 month, 2 months and 3 months from the baseline for recording clinical observations, and radiographic parameters were recorded at the end of the study. STATISTICAL ANALYSIS: Mean, standard deviation, Chi-square test, "t" test for equality of means and paired samples correlations were used. RESULTS: There was a statistically significant clinical attachment gain, reduction in bleeding index scores, probing pocket depth reduction and bone gain in both the groups, but group B showed better results than group A, and these differences were statistically significant. CONCLUSIONS: The results of this study show that chlorhexidine chip (PerioCol-CG) is an effective adjunctive therapy to scaling and root planing in the treatment of chronic periodontitis. PMID- 21976839 TI - A comparative evaluation of hepatocyte growth factor levels in gingival crevicular fluid and saliva and its correlation with clinical parameters in patients with and without chronic periodontitis: A clinico-biochemical study. AB - OBJECTIVES: The purpose of the present study was to evaluate and compare the relationship between the levels of hepatocyte growth factor (HGF) in gingival crevicular fluid (GCF) and saliva, both clinically and biochemically, in patients with and without chronic periodontitis. MATERIALS AND METHODS: For this study, 36 patients (12 male, 24 female) were selected in the age range of 18-60 years (mean, 32.7+/-11.1 years). The subjects were assigned to three groups, which included Group I (control), Group II (chronic periodontitis with probing depth PD <5 mm), and Group III (chronic periodontitis with PD >=5 mm). Clinical parameters included plaque index, gingival index, sulcus bleeding index, PD, and clinical attachment level. The GCF samples were taken by using the capillary tubes whereas saliva was collected by the suction method. The levels of HGF in GCF and in saliva were estimated using an enzyme linked immunosorbant assay reader. RESULTS: There was a significant correlation in the levels of HGF in GCF and in saliva of patients with and without chronic periodontitis. The results also indicated that the HGF levels in GCF and saliva correlated well with the clinical parameters and with the severity of the periodontal disease. CONCLUSION: Both GCF and saliva can be used to estimate the levels of HGF and thus may be regarded as a novel marker for periodontal disease activity. PMID- 21976840 TI - Myeloperoxidase staining in the diagnosis of aggressive periodontitis. AB - AIMS: To evaluate neutrophil myeloperoxidase (MPO) staining procedure as a reliable, affordable and easily available diagnostic assay for aggressive periodontitis. MATERIALS AND METHODS: Fifteen subjects were recruited in the study wherein five each were diagnosed as aggressive periodontitis and chronic periodontitis respectively, and five were periodontally healthy. Three millilitres (ml) of venous blood was collected using Vacutainers containing ethylene diamine tetra acetate (EDTA) and was subjected to MPO staining procedure. Histological picture was evaluated using a visual analogue scale (VAS). RESULTS: MPO stained specimen of all the patients showed positive MPO staining of the neutrophils. The intensity of the stain of MPO granules was more in aggressive periodontitis specimen as compared to the chronic periodontitis patient specimen and healthy subject specimen. The staining characteristics were comparable for chronic periodontitis patients and healthy subject. CONCLUSIONS: This study shows that there is a potential and probable place for MPO staining as an economical, relatively convenient and easily available assay in the diagnosis of aggressive periodontitis. PMID- 21976841 TI - Clinical evaluation of the efficacy of a GTR membrane (HEALIGUIDE) and demineralised bone matrix (OSSEOGRAFT) as a space maintainer in the treatment of Miller's Class I gingival recession. AB - BACKGROUND: Periodontal plastic surgical procedures aimed at coverage of exposed root surface have evolved into routine treatment modalities. The present study was designed to evaluate the effectiveness and predictability of using a collagen barrier along with a demineralized bone matrix in the treatment of recession defects in a single surgical procedure. MATERIALS AND METHODS: Seventeen patients with Miller's class I recession were treated with a combination of a collagen barrier used along with a bone graft and coronally advanced flap technique. Clinical parameters were recorded at baseline, 3 months, 6 months, and 9 months. RESULTS: The study showed a highly significant reduction in the recession depth (70.29 +/- 21.96%) at the end of the study. This study showed that the use of this technique for recession coverage is highly predictable and highly esthetic root coverage can be obtained. PMID- 21976842 TI - Split mouth de-epithelization techniques for gingival depigmentation: A case series and review of literature. AB - Gingival melanin pigmentation occurs in all races of mankind. Although clinical melanin pigmentation does neither present itself as a medical problem nor a disease entity, it is a major esthetic concern for many people, especially Asians. Esthetic gingival depigmentation procedures can be performed in such patients with excellent results. This case series presents a split mouth de epithelization procedure using popular surgical techniques such as scalpel, bur abrasion or electrosurgery. These techniques were successfully used to treat gingival hyperpigmentation. Although we found that electrosurgery increased the efficacy of our work, giving a cleaner and neater work field, it required a lot of precision. In contrast, scalpel de-epithelization was easy and technique friendly, giving excellent results and patient satisfaction. However, the cases are being followed-up to study the factors affecting the rate and length of time required for repigmentation and to study the repigmentation patterns. This case series also reviews the advantages and disadvantages of various techniques available for depigmentation, and reiterates that the scalpel technique still serves as a gold standard for depigmentation. PMID- 21976843 TI - Palatogingival groove - a silent killer: Treatment of an osseous defect due to it. AB - A male patient of 21 years of age reported to the Department of Periodontology and Implantology with a chief complain of pus discharge in both right and left upper lateral incisors. On clinical examination a deep pocket of about 10-14 mm was noticed in both lateral incisors. Radiographic interpretation shows a teardrop-shaped radiolucency in both the laterals giving suspicion of palatogingival groove, which was later discovered and treated surgically. PMID- 21976844 TI - Report of a case of Turner's syndrome with localized aggressive periodontitis. AB - Turner's syndrome is a disorder in females characterized by the absence of all or part of a normal second sex chromosome. It is typically characterized by the combination of physical features and cytogenetics in females. Physical features include short stature, primary amenorrhea, hypogonadism, low hair line at the back of the neck, and digital anomalies. Most affected patients have a 45XO monosomy, but the presence of an abnormal chromosome or mosaicism of 45X with another cell line can also fulfill the criteria. Features seen in the oral cavity of patients diagnosed with Turner's syndrome include high palatal vault, hypoplastic mandible, prematurely erupting teeth, and orthodontic anomalies. A case of Turner's syndrome with localized aggressive periodontitis has been reported here. PMID- 21976845 TI - A sequential approach in treatment of perio-endo lesion. AB - The success of a combined periodontal and endodontic lesion depends on the elimination of both of these disease processes. In the case of a combined endo perio lesion, the endodontic therapy results in healing of the endodontic component of involvement while the prognosis of tooth would finally depend on the healing of the periodontal structures. This case report evaluates the efficacy of bioactive glass in the management of furcation defect associated with an endo perio lesion in a right mandibular first molar. A 22-year-old male patient with an endo-perio lesion in the right mandibular first molar was initially treated with endodontic therapy. Following the endodontic treatment, the furcation defect was treated using bioactive glass in a putty form. At the end of 9 months, there was a gain in the clinical attachment level and reduction in probing depth. Radiographic evidence showed that there was a significant bony fill. PMID- 21976846 TI - Individualized interventional pain management technique in early stage of cancer pain: a desirable protocol for improving quality of life. PMID- 21976847 TI - Evaluation and management of fatigue in oncology: a multidimensional approach. AB - Fatigue, one of the most common symptoms experienced by cancer patients, is multidimensional and is associated with significant impairment in functioning and overall quality of life. Although the precise pathophysiology of cancer-related fatigue (CRF) is not well understood, a number of metabolic, cytokine, neurophysiologic, and endocrine changes have been described in these patients. A better understanding of these abnormalities is likely to lead to novel therapeutic interventions. Clinically, all patients presenting with significant fatigue should be evaluated for treatable conditions that might contribute to this symptom. Exercise and treatment of anemia are the two most established interventions for CRF. Psychostimulants seem promising based on early studies. Several complementary medicine treatments that showed efficacy in preliminary studies merit further testing. PMID- 21976849 TI - Is there a Role of Palliative Care in the Neonatal Intensive Care Unit in India? AB - Recent advances in medical care have improved the survival of newborn babies born with various problems. Despite this death in the neonatal intensive care unit (NICU) is an inevitable reality. For babies who are not going to "get better," the health care team still has a duty to alleviate the physical suffering of the baby and to support the family. Palliative care is a multidisciplinary approach to relieve the physical, psycho social, and spiritual suffering of patients and their families. Palliative care provision in the Indian NICU settings is almost nonexistent at present. In this paper we attempt to "build a case" for palliative care in the Indian NICU setting. PMID- 21976848 TI - An update in the management of malignant pleural effusion. AB - Malignant pleural effusion (MPE) usually presents in the disseminated and advanced stage of malignancy. Dyspnea is the debilitating symptom which needs palliation in these patients. Various modalities are available in the management of MPE. Careful consideration of the patient's expected survival and quality of life is needed when deciding the optimum treatment modality in such patients. In this article, different modalities of the palliative management of MPE are discussed with an attempt to derive a treatment algorithm for the management of MPE. PMID- 21976850 TI - Utilization of brief pain inventory as an assessment tool for pain in patients with cancer: a focused review. AB - The Pain Research Group of the world health organization (WHO) Collaborating Centre for Symptom Evaluation in Cancer Care had developed the Brief Pain Inventory (BPI), a pain assessment tool for use with cancer patients. The BPI measures both the intensity of pain (sensory dimension) and interference of pain in the patient's life (reactive dimension). The objective of this review paper was to provide a detailed update of existing evidence on applicability of BPI in evaluation of patients with cancer pain. The BPI demonstrated good construct and concurrent validity. It was translated and validated into many languages - Brazilian, Chinese, Greek, Hindi, Italian, Japanese, Korean, Malay, Norwegian, Polish, Russian, Spanish, Taiwanese and Thai. The BPI was validated in patient populations such as bone metastases, breast cancer and postoperative cancer patients. The BPI can be used both as a quantitative or a qualitative measure for statistical analysis. The BPI was a powerful tool and, having demonstrated both reliability and validity across cultures and languages, was being adopted in many countries for clinical pain assessment, epidemiological studies, and in studies on the effectiveness of pain treatment. Future studies are warranted on its responsiveness and cross-cultural adaptation into other cancer pain syndromes and into other Indian languages. PMID- 21976852 TI - Cancer pain management: basic information for the young pain physicians. AB - Cancer pain is multifactorial and complex. The impact of cancer pain is devastating, with increased morbidity and poor quality of life, if not treated adequately. Cancer pain management is a challenging task both due to disease process as well as a consequence of treatment-related side-effects. Optimization of analgesia with oral opioids, adjuvant analgesics, and advanced pain management techniques is the key to success for cancer pain. Early access of oral opioid and interventional pain management techniques can overcome the barriers of cancer pain, with improved quality of life. With timely and proper anticancer therapy, opioids, nerve blocks, and other non-invasive techniques like psychosocial care, satisfactory pain relief can be achieved in most of the patients. Although the WHO Analgesic Ladder is effective for more than 80% cancer pain, addition of appropriate adjuvant drugs along with early intervention is needed for improved Quality of Life. Effective cancer pain treatment requires a holistic approach with timely assessment, measurement of pain, pathophysiology involved in causing particular type of pain, and understanding of drugs to relieve pain with timely inclusion of intervention. Careful evaluation of psychosocial and mental components with good communication is necessary. Barriers to cancer pain management should be overcome with an interdisciplinary approach aiming to provide adequate analgesia with minimal side-effects. Management of cancer pain should comprise not only a physical component but also psychosocial and mental components and social need of the patient. With risk-benefit analysis, interventional techniques should be included in an early stage of pain treatment. This article summarizes the need for early and effective pain management strategies, awareness regarding pain control, and barriers of cancer pain. PMID- 21976853 TI - Palliative care in enugu, Nigeria: challenges to a new practice. AB - Everyone, young and old, male and female, rich and poor, should have access to excellent care during the course of a serious illness and at the end of life. Therefore, a denial of such care becomes an infringement of the individual's human rights. Because of the efforts of pioneers in this field of Medicine in Africa and beyond, both living and immortalized, we can now say that palliative care in the African context is affordable and achievable. In this article, some of the challenges faced in setting up and running a new palliative care practice in an emerging and developing economy are examined. PMID- 21976851 TI - Cancer Pain: A Critical Review of Mechanism-based Classification and Physical Therapy Management in Palliative Care. AB - Mechanism-based classification and physical therapy management of pain is essential to effectively manage painful symptoms in patients attending palliative care. The objective of this review is to provide a detailed review of mechanism based classification and physical therapy management of patients with cancer pain. Cancer pain can be classified based upon pain symptoms, pain mechanisms and pain syndromes. Classification based upon mechanisms not only addresses the underlying pathophysiology but also provides us with an understanding behind patient's symptoms and treatment responses. Existing evidence suggests that the five mechanisms - central sensitization, peripheral sensitization, sympathetically maintained pain, nociceptive and cognitive-affective - operate in patients with cancer pain. Summary of studies showing evidence for physical therapy treatment methods for cancer pain follows with suggested therapeutic implications. Effective palliative physical therapy care using a mechanism-based classification model should be tailored to suit each patient's findings, using a biopsychosocial model of pain. PMID- 21976854 TI - An evaluation of the implementation of integrated community home-based care services in vhembe district, South Africa. AB - AIM: The aim of the study is to evaluate the implementation of integrated community home-based care (CHBC) services in Vhembe District, Limpopo Province, South Africa. MATERIALS AND METHODS: In all, 393 caregivers responded to a questionnaire on various aspects of home-based care and service provider characteristics. RESULTS: Results indicate that in most areas of the Community Homes-based Care (CHBC) services, caregivers had confidence including wound dressing, health education, bet bathing, giving prescribed medication, and management of diabetes client, and they had sufficient knowledge received through training. Lower knowledge and confidence was noted for the management of hypertensive and asthmatic clients, and lower knowledge (82%) was indicated for counseling. The most common caregiving services included health education (100%), giving medication (98%), management of hypertension (22%), and counseling (15%). Most caregivers rated the implementation of CHBC in their district as excellent or good (70%). The most common problems and barriers in caregiving included (1) structural problems: none or sometimes not available home-based care kits (54%), lack of resources (32%), lack of transport money (30%), and very low stipend (22%); (2) problems with the supervisor such as "lack of management skills" (40%) and "selfishness" (38%); and (3) problems with clients and community such as "patients not taking prescribed medicines regularly" (45%) and "not welcomed by patients and family members" (35%). CONCLUSION: Community home-based caregivers are largely able to implement home-based care services but would need more support (training, financial, career structure, and health system) to improve on their services. PMID- 21976855 TI - Low molecular weight heparin: a practical approach in deep venous thrombosis in palliative care. AB - INTRODUCTION: Deep vein thrombosis (DVT) is one of the many cause of pain in advance cases of carcinoma cervix. The most widely used agent for combating DVT is unfractionated heparin. AIMS: Aims of this study is to see the efficacy of the use of low molecular weight (LMW) haparin and its practical utility in palliative care settings. MATERIALS AND METHODS: Twelve cases of established DVT received enoxaparin at 40 mg/m with warfarin. RESULTS: There was 70% resolution of limb swelling in seven cases. Out of remaining four cases took two months to resolve and one case did not resolve completely. CONCLUSIONS: LMV heparin is effective in palliative care setting and also has added advantage of subcutaneous route of administration. PMID- 21976856 TI - Hypnotherapy: fact or fiction: a review in palliative care and opinions of health professionals. AB - CONTEXT: Complementary medicine like hypnotherapy is often used for pain and palliative care. Health professionals vary in views about hypnotherapy, its utility, value, and attitudes. AIMS: To understand the opinions of health professionals on hypnotherapy. SETTINGS AND DESIGN: A semi-qualitative method to survey opinions of the health professionals from various disciplines attending a programme on hypnotherapy was conducted. MATERIALS AND METHODS: The survey form consisted of 32 statements about hypnosis and hypnotherapy. Participants were asked to indicate whether they agreed, disagreed, or were not sure about each statement. A qualitative feedback form was used to obtain further views about hypnotherapy. STATISTICAL ANALYSIS USED: Percentage, frequency distribution. RESULTS: The sample consisted of 21 participants from various disciplines. Two thirds of the participants gave correct responses to statements on dangerousness of hypnosis (90%), weak mind and hypnosis (86%), and hypnosis as therapy (81%). The participants gave incorrect responses about losing control in hypnosis (57%), hypnosis being in sleep (62%), and becoming dependent on hypnotist (62%). Participants were not sure if one could not hear the hypnotist one is not hypnotized (43%) about the responses on gender and hypnosis (38%), hypnosis leading to revealing secrets (23%). CONCLUSIONS: Despite patients using complementary medicine services, often health professionals are unaware of the issues associated with these services. These myths may interfere in using hypnotherapy as therapeutic tool in palliative care. It is important for health professionals to have an appropriate and evidence-based understanding about the complementary therapies including hypnotherapy. PMID- 21976857 TI - Awareness and impact of education on breast self examination among college going girls. AB - INTRODUCTION: Breast cancer accounts for 19-34% of all cancer cases among women in India. There is high mortality due to late stage diagnosis as patients usually present at an advanced stage because of lack of awareness and nonexistent breast cancer screening programs. Early detection and prompt treatment offer the greatest chance of long-term survival and breast self-examination (BSE) seems to be a important viable optional substitute for early detection of cancer. OBJECTIVES: 1) To assess the level of knowledge of degree college female students on BSE. 2) To determine the effectiveness of planned teaching program among degree college female students on BSE. 3) To find the association between pretest knowledge and selected demographic variables. MATERIALS AND METHODS: Pre experimental one group pretestpost-test design was carried out among 40 degree female students by using cluster sampling method from selected colleges of Udupi district. RESULTS: The data analyzed showed that majority (52%) of them was in the age group of 18-19 years and 72% of them were had average knowledge on BSE in the pretest score. Out of 40 participants only one student was performing BSE occasionally. CONCLUSIONS: Awareness regarding breast self examination among young generations is useful and it is the most important viable tool for early detection. PMID- 21976858 TI - Neuropathic pain: a personal case reflection on a critical incident. AB - Neuropathic pain is a distressing symptom for the patient and a difficult symptom for the physician to treat. There is lack of evidence-based clinical guidelines for the management of malignant neuropathic pain. The case reflection is a personal account of what has been learnt from a critical incident in a particular patient in the management of neuropathic pain. Psychological issues are known to increase pain percetion and affect the quality of life. The case reflection explores problem areas, defines lacunae in knowledge, and demonstrates active learning of the management of neuropathic pain through reflective practice. PMID- 21976859 TI - Homecare-based Motor Rehabilitation in Musculoskeletal Chronic Graft Versus Host Disease. AB - Chronic graft versus host disease (cGVHD) is a frequent complication of allogeneic stem cell transplantation. Extensive musculoskeletal and skin involvement may induce severe functional impairment, disability and quality of life deterioration. Physical rehabilitation is recommended as ancillary therapy in these forms, but experiences are sparse. A 39-year-old man affected by musculoskeletal and skin chronic graft versus host disease (cGVHD) was treated with a homecare-based motor rehabilitation program during palliation for disease progression. Significant functional improvement was obtained. Motor rehabilitation should be strongly considered for patients with musculoskeletal cGVHD, both in the palliative and in the curative phase of disease. PMID- 21976860 TI - Successful management of a difficult cancer pain patient by appropriate adjuvant and morphine titration. AB - Morphine has been used for many years to relieve cancer pain. Oral morphine (in either immediate release or modified release form) remains the analgesic of choice for moderate or severe cancer pain. The dose of oral morphine is titrated up to achieve adequate relief from pain with minimal side effects. Antidepressant and anticonvulsant drugs, when used in addition to conventional analgesics, give excellent relief from cancer pain. Most cancer pain responds to pharmacological measures with oral morphine but some pain like neuropathic and bony pain, pain in children and elderly age group, and advanced malignancy pain are very difficult to treat. Here, we report the management of a similar patient of severe cancer pain and the difficulty that we came across during dose titration of oral morphine and adjuvant analgesic. PMID- 21976861 TI - Management of Peritoneal Dialysis within a Home Care Program for Hematological Malignancies: Concerns and Perspectives Illustrated by a Case Report. AB - The case of an 86-year-old man suffering from acute myeloid leukemia and end stage renal disease, managed at home, with continuous peritoneal dialysis regimen, is described. PMID- 21976862 TI - Stalwart approach to stall wart. PMID- 21976863 TI - Effect of yoga and ayurveda on duchenne muscular dystrophy. PMID- 21976864 TI - VSDK: Virtual screening of small molecules using AutoDock Vina on Windows platform. AB - Screening of ligand molecules to target proteins using computer-aided docking is a critical step in rational drug discovery. Based on this circumstance, we attempted to develop a virtual screening application system, named VSDK Virtual Screening by Docking, which can function under the Windows platform. This is a user-friendly, flexible, and versatile tool which can be used by users who are familiar with Windows OS. The virtual screening performance was tested for an arbitrarily-selected receptor, FGFR tyrosine kinase (pdb code: 1agw), by using ligands downloaded from ZINC database with its grid size of x,y,z = 30,30,30 and run number of 10. It took 90 minutes for 100 molecules for this virtual screening. VSDK is freely available at the designated URL, and a simplified manual can be downloaded from VSDK home page. This tool will have a more challenging scope and achievement as the computer speed and accuracy are increased and secured in the future. AVAILABILITY: The database is available for free at http://www.pharm.kobegakuin.ac.jp/~akaho/english_top.html. PMID- 21976865 TI - How do we define success in pediatric cardiac care? PMID- 21976866 TI - The role of the Fontan operation in the treatment of congenitally corrected transposition of the great arteries. AB - Congenitally corrected transposition of the great arteries (ccTGA) is a complex cardiac anomaly with an unfavorable natural history. Surgical treatment has been available for over 50 years. Initial procedures used for ccTGA did not correct atrio-ventricular discordance, leaving the right ventricle in systemic position. In the past two decades anatomic repair has been considered to be a better option. Many cases subjected to anatomic repairs would also be suitable for the Fontan strategy, which probably has a lower initial risk. The rationale for use of the Fontan operation in management of congenitally corrected transposition is discussed in this review, with comparisons to other strategies. PMID- 21976867 TI - Assessing the influence of consanguinity on congenital heart disease. AB - Numerous articles have been published linking consanguineous marriage to an elevated prevalence of congenital heart disease, with ventricular septal defects and atrial septal defects the most commonly cited disorders. While initially persuasive, on closer examination many of these studies have fundamental shortcomings in their design and in the recruitment of study subjects and controls. Improved matching of cases and controls, to include recognition of the long-established community boundaries within which most marriages are contracted, and the assessment of consanguinity within specific levels and types of marital union would improve and help to focus the study outcomes. At the same time, major discrepancies between studies in their reported prevalence and types of congenital heart disease suggest an urgent need for greater standardization in the classification and reporting of these disorders. PMID- 21976868 TI - Risk factors predisposing to congenital heart defects. AB - INTRODUCTION: Congenital heart disease (CHD) is associated with multiple risk factors, consanguinity may be one such significant factor. The role of consanguinity in the etiology of CHD is supported by inbreeding studies, which demonstrate an autosomal recessive pattern of inheritance of some congenital heart defects. This study was done to find out the risk factors for CHD. METHODS: A case-control study was done on pediatric patients at a tertiary care hospital, Aga Khan University Hospital, located in Karachi, Pakistan. A total of 500 patients, 250 cases and 250 controls were included in the study. RESULTS: Amongst the 250 cases (i.e. those diagnosed with CHD), 122 patients (48.8%) were born of consanguineous marriages while in the controls (i.e. non-CHD) only 72 patients (28.9%) showed a consanguinity amongst parents. On multivariate analysis, consanguinity emerged as an independent risk factor for CHD; adjusted odds ratio 2.59 (95% C. I. 1.73 - 3.87). Other risk factors included low birth weight, maternal co-morbidities, family history of CHD and first born child. On the other hand, medications used by the mother during the index pregnancy, maternal age and gender of the child did not significantly increase the risk of developing CHD. CONCLUSIONS: Analyses of our results show that parental consanguinity, family history of CHD, maternal co-morbidities, first born child and low birth weight are independent risk factors for CHD. PMID- 21976870 TI - Pediatric cardiac intensive care units: The way forward. PMID- 21976869 TI - Dedicated pediatric cardiac intensive care unit in a developing country: Does it improve the outcome? AB - INTRODUCTION AND AIM: Focussed cardiac intensive care is known to produce better outcomes. We have evaluated the benefits of a dedicated Pediatric Cardiac Intensive Care Unit (PCICU) in the early postoperative outcomes of patients undergoing surgery for congenital heart disease. METHODS: Prospectively collected data of 634 consecutive patients who underwent congenital heart surgery from September 2008 to September 2009 were analyzed. Midway through this period a dedicated PCICU was started. The patients who were treated in this new PCICU formed the study group (Group B, n = 318). The patients who were treated in a common postoperative cardiac surgery ICU formed the control group (Group A, n = 316). Early postoperative outcomes between the two groups were compared. RESULTS: The two groups were comparable with respect to demographic data and intraoperative variables. The duration of mechanical ventilation in the dedicated pediatric cardiac ICU group (32.22 +/- 52.02 hours) was lower when compared with the combined adult and pediatric surgery ICU group (42.92 +/- 74.24 hours, P= 0.04). There was a shorter duration of ICU stay in the dedicated pediatric cardiac ICU group (2.69 +/- 2.9 days vs. 3.43 +/- 3.80 days, P = 0.001). The study group also showed a shorter duration of inotropic support and duration of invasive lines. The incidence of blood stream infections was also lower in the dedicated pediatric ICU group (5.03 vs. 9.18%, P = 0.04). A subgroup analysis of neonates and infants <1 year showed that the advantages of a dedicated pediatric intensive care unit were more pronounced in this group of patients. CONCLUSIONS: Establishment of a dedicated pediatric cardiac intensive care unit has shown better outcomes in terms of earlier extubation, de-intensification, and discharge from the ICU. Blood stream infections were also reduced. PMID- 21976871 TI - Myocardial tissue Doppler velocities in fetuses with hypoplastic left heart syndrome. AB - BACKGROUND: Tissue Doppler Imaging (TDI) is a sensitive index of myocardial function. Its role in the fetus has not been extensively evaluated. OBJECTIVE: To compare myocardial tissue Doppler velocities in fetuses with hypoplastic left heart syndrome (HLHS) to those of normal fetuses (matched for gestational age.) METHODS: Cross-sectional retrospective study conducted at 2 large perinatal centers (2003-2007). Fetuses with HLHS (n = 13) were compared with normal fetuses (n = 207) in 5 gestational age groups. TDI data included peak systolic (s'), peak early (e'), and late diastolic velocities (a'). Linear regression was used to compare TDI parameters in fetuses with HLHS to normal fetuses matched for gestational age. RESULTS: Fetuses with HLHS had significantly reduced lateral tricuspid annular e' as compared to normal fetuses. Both normal fetuses and those with HLHS had linear increase in TDI velocities with advancing gestational age. CONCLUSIONS: TDI velocities are abnormal in fetuses with HLHS. TDI can be useful in serial follow-up of cardiac function in fetuses with HLHS. PMID- 21976872 TI - Ductal recanalization and stenting for late presenters with TGA intact ventricular septum. AB - INTRODUCTION: The ideal management strategy for patients presenting late with transposition of great arteries (TGA), intact ventricular septum (IVS), and regressed left ventricle (LV) is not clear. Primary switch, two-stage switch, and Senning operation are the options. Left ventricular retraining prior to arterial switch by ductal stenting may be effective, but the experience is very limited. METHODS: Five of six children aged 3-6 months with TGA-IVS and regressed LV underwent recanalization and transcatheter stenting of ductus arteriosus. The ductal stent was removed during arterial switch surgery. RESULTS: The procedure was successful in 5/6 patients. All the patients had totally occluded ductus and needed recanalization with coronary total occlusion hardware. The ductus was dilated and stented with coronary stents. In all the patients, there was significant luminal narrowing despite adequate stent placement and deployment. Two patients needed reintervention for abrupt closure of the stent. Ductal stenting resulted in left ventricular preparedness within 7-14 days. One patient died of progressive sepsis after 14 days of stenting, even though the LV was prepared. Four patients underwent successful uneventful arterial switch surgery. During surgery, it was observed that the mucosal folds of duct were protruding through the struts of the stent in one patient. CONCLUSIONS: Ductal stenting is a good alternative strategy for left ventricular retraining in TGA with regressed LV even in patients with occluded ducts. PMID- 21976873 TI - Percutaneous closure of patent ductus arteriosus in children: Immediate and short term changes in left ventricular systolic and diastolic function. AB - OBJECTIVE: To evaluate the effect of percutaneous closure of patent ductus arteriosus (PDA) on left ventricular (LV) systolic and diastolic function in children. BACKGROUND: Limited studies are available on alteration in LV hemodynamics, especially diastolic function, after PDA closure. METHODS: Thirty two consecutive children with isolated PDA treated by trans-catheter closure were studied. The LV systolic and diastolic function were assessed by two-dimensional (2D) echocardiography and tissue Doppler imaging 1 day before the PDA closure, on day 1, and on follow-up. RESULTS: At baseline, none of the patients had LV systolic dysfunction. On day 1 post-PDA closure, 8 (25%) children developed LV systolic dysfunction. The baseline LV ejection fraction (LVEF), LV end-systolic dimension (LVESD), and PDA diastolic gradient predicted the post-closure LVEF. Patients who developed post-closure LV systolic dysfunction had poorer LV diastolic function than those who did not. LV diastolic properties improved after PDA closure; however, the improvement in LV diastolic properties lagged behind the improvement in the LV systolic function. All children were asymptomatic and had normal LVEF on follow up of >3 months. CONCLUSIONS: Percutaneous closure of PDA is associated with the reversible LV systolic dysfunction. Improvement in the LV diastolic function lags behind that in the LV systolic function. PMID- 21976874 TI - Short-term outcome comparison of Norwood procedures with right ventricle to pulmonary artery conduit versus modified Blalock-Taussig shunt: A meta-analysis. AB - A small number of nonrandomized and retrospective studies have compared outcomes of classical Norwood procedures for hypoplasticleft-heart syndrome and single ventricle lesions involving a Blalock-Taussig (BT) shunt to the modified procedure using a right ventricle to pulmonary artery conduit. Some of these studies reported data for the same outcomes and a meta-analysis was done to analyze pooled outcomes comparing in-hospital mortality, interstage mortality, cardiopulmonary bypass time, systolic and diastolic blood pressures 24 h postoperatively, length of intensive care and hospital stay, and need for postoperative extracorporeal membrane oxygenation. Right ventricle to pulmonary artery conduit was associated with an insignificant reduction of in-hospital mortality (odds ratio, 0.674, 95% confidence interval, 0.367 to 1.238), and in the length of hospital stay. There were significant reductions in cardiopulmonary bypass time, length of intensive care unit stay, and need for postoperative extracorporeal membrane oxygenation, postoperative ventilation times, and interstage mortality (odds ratio, 0.191, confidence interval, 0.0620 to 0.587). There was a significant increase in diastolic blood pressure and an insignificant increase in systolic blood pressure 24 h postoperatively. This pooled analysis demonstrates potential advantages associated with the right ventricle to pulmonary artery conduit when compared to the modified BT shunt in palliation and demonstrates the need for large randomized controlled trials that compare a number of outcomes in both procedures. PMID- 21976875 TI - Right ventricle to pulmonary artery shunt modification of Norwood procedure: Outcomes, concerns, and controversies. PMID- 21976876 TI - Hypocalcemic cardiomyopathy presenting as cardiogenic shock. AB - Hypocalcemia is a less known but treatable cause for dilated cardiomyopathy, leading to severe heart failure in children. Cardiogenic shock related to hypocalcemic cardiomyopathy is a rare event. We describe 5 infants presenting with cardiogenic shock over 3 years, who were found to have severe hypocalcemia as a sole cause of myocardial dysfunction. The patients responded to calcium and vitamin D supplementation promptly and left ventricular systolic function normalized within months of treatment. In any case of cardiogenic shock, hypocalcemia should be included in the differential diagnosis and must be investigated. PMID- 21976877 TI - Can troponin T levels be useful in the diagnosis of rheumatic carditis? AB - OBJECTIVE: Acute rheumatic fever (ARF) is an endemic disease observed in children of developing countries. The purpose of this study was to test if it was possible to identify myocardial involvement in cases with rheumatic carditis by the measurement of serum cardiac TnT. METHODS: 30 patients diagnosed as ARF underwent echocardiography and their cardiac troponin T (cTnT) serum levels were measured. Patients were divided into group 1: Arthritis alone, group 2: carditis, and group 3 carditis with congestive heart failure (CHF). RESULTS: cTnT serum levels were normal in all except one patient with in group 3. Two patients in carditis (group 2) and three patients in CHF (group 3) had dilation in left ventricular end diastolic diameter. CONCLUSIONS: Normal cTnT levels in our patient group suggests that inflammation rather than myocardial necrosis is predominant in ARF carditis. PMID- 21976878 TI - Symptomatic aneurysm of ductus arteriosus in neonates. AB - Four neonates presented within 24 hours of birth with stridor, respiratory distress and a weak cry. Clinical examination of the cardiovascular system revealed no abnormality. The transthoracic echocardiogram showed large aneurysm of ductus arteriosus at the aortic isthmus, tapering to a small tortuous channel at the site of pulmonary artery insertion. Computerized tomography scan performed in two of the neonates demonstrated considerable compression of adjacent thoracic structures. One required surgical excision due to persistence of symptoms. Serial echocardiograms in the remaining three babies showed transition through various stages of resolution over a period of 6 weeks to 3 months, resulting in the obliteration of the aneurysm. All babies are doing well during the follow-up. PMID- 21976879 TI - Temporary neonatal atrial pacing through the umbilical venous route: A novel technique. AB - Atrial pacing in the neonate is rarely done due to constraints of equipment, technical knowhow, and risk of complications. We describe a novel method of atrial pacing in the new born using equipment readily available in any intensive care unit. Atrial pacing can be achieved using an adult bipolar pacing wire directly introduced through the umbilical venous route. We have used this method in 5 neonates, and achieved atrial capture in 4 patients. Temporary atrial pacing is a therapeutic option in a few neonatal arrhythmias, such as atrial flutter, a few types of re-entrant tachycardias, such as accessory pathway mediated tachycardia and junctional reciprocating tachycardia, and has a limited role in cardiopulmonary resuscitation where sinoatrial node dysfunction is suspected. PMID- 21976880 TI - Childhood cardiovascular risk factors in South Asians: A cause of concern for adult cardiovascular disease epidemic. AB - Cardiovascular risk factors in children are increasing at an alarming rate in the western world. However, there is limited information regarding these in the South Asian children. This review attempts at summarizing such evidence. South Asians are remarkable for the earlier onset of adult cardiovascular disease (CVD) by almost a decade compared to the Caucasians. We identified published literature, mainly on PubMed, Embase and Cochrane library using specific search terms such as lipid abnormalities, high blood pressure, hyperglycemia, tobacco use, obesity, physical inactivity, and unhealthy dietary practices. Atherosclerotic CVD processes begin early in childhood and are influenced over the life course by genetic and potentially modifiable risk factors and environmental exposure. 80% of adult CVD burden will fall on the developing nations by 2020. The concept of primordial prevention is fast emerging as a necessary prevention tool to curb adult CVD epidemic. Established guidelines and proven preventive strategies on cardiovascular health exist; however, are always implemented half-heartedly. Composite screening and prediction tools for adults can be adapted and validated in children tailored to South Asian population. South Asian children could be at a greater risk of developing cardiovascular risk factors at an earlier stage, thus, timely interventions are imperative. PMID- 21976881 TI - The developing role of fetal magnetic resonance imaging in the diagnosis of congenital cardiac anomalies: A systematic review. AB - Advances in the fetal magnetic resonance imaging (MRI) over the last few years have resulted in the exploring the use of fetal MRI to detect congenital cardiac anomalies. Early detection of congenital cardiac anomalies can help more appropriately manage the infant's delivery and neonatal management. MRI offers anatomical and functional studies and is a safe adjunct that can help more fully understand a fetus' cardiac anatomy. It is important for the obstetricians and pediatric cardiologists to be aware of the recent advancements in fetal MRI and it's potential utility in diagnosing congenital cardiac anomalies. PMID- 21976882 TI - Understanding the physiology of complex congenital heart disease using cardiac magnetic resonance imaging. AB - Complex congenital heart diseases are often associated with complex alterations in hemodynamics. Understanding these key hemodynamic changes is critical to making management decisions including surgery and postoperative management. Existing tools for imaging and hemodynamic assessment like echocardiography, computed tomography and cardiac catheterization have inherent limitations. Cardiac magnetic resonance imaging (MRI) is emerging as a powerful bouquet of tools that allow not only excellent imaging, but also a unique insight into hemodynamics. This article introduces the reader to cardiac MRI and its utility through the clinical example of a child with a complex congenital cyanotic heart disease. PMID- 21976883 TI - Levoatriocardinal vein with normal intracardiac anatomy and pulmonary venous return. AB - Levoatriocardinal vein (LACV) is characterized by an abnormal connection between pulmonary and systemic venous return. This extremely rare cardiac malformation is usually associated with left-sided obstructive lesions including mitral atresia, hypoplastic left-heart syndrome, and abnormal pulmonary venous connection. Patients may have low systemic cardiac output and pulmonary venous obstruction symptoms. In this manuscript, we report a case with LACV and normal pulmonary venous return with absence of any intracardiac pathology. LACV was demonstrated with echocardiography, angiography, and computed tomography. Surgical correction was made successfully. PMID- 21976884 TI - Cardiac calcification in acute intermittent porphyria. AB - Aetiology of pericardial calcifications can be multifactorial. Tuberculosis has been reported as the most common cause. Other known causes include uraemia, asbestosis, post-traumatic or postoperative. We report a rare case of pericardial calcification seen in a patient with established acute intermittent porphyria. A direct causal relationship cannot be established between porphyria and pericardial calcification, but it may be due to deposition of the porphyrin in the pericardium. PMID- 21976885 TI - Aneurysm of the left aortic sinus causing acute myocardial infarction. AB - This report describes the findings and management of a young male who presented with an acute ST-segment elevation myocardial infarction due to compression of the circumflex coronary artery by a large aneurysm of left sinus of Valsalva. PMID- 21976886 TI - Iatrogenic intra-atrial macro-reenterant tachycardia following transcatheter closure of atrial septal defect treated by radiofrequency ablation. AB - Percutaneous closure of an atrial septal defect (ASD) has been established as a safe and effective alternative to surgical management. We describe a case of a 41 year-old patient in whom an Amplatzer septal occluder device was used to close a moderately large ASD and who subsequently developed incessant intra-atrial macro reenterant tachycardia. The tachycardia was terminated by radiofrequency ablation guided by electroanatomical mapping. PMID- 21976887 TI - Device occlusion of pseudoaneurysm of ascending aorta. AB - Pseudoaneurysm of ascending aorta is an infrequent but well-recognized and potentially fatal complication after cardiac surgeries. The complication can develop early, delayed or late, and the presentation is also varied. We are presenting here two cases of pseudoaneurysm of ascending aorta following cardiac surgery that were successfully managed by the transcatheter method. The first one occurred following coronary artery bypass surgery and the second one occurred following double-valve replacement surgery. The aortic openings of these aneurysms were occluded with 12 mm and 10 mm atrial septal occluders, respectively, with a good outcome. An immediate postprocedure angiogram showed no residual flow into the sac. Six months of follow-up of both cases also showed excellent results. PMID- 21976888 TI - Cor triatriatum and coronary artery fistula in tetralogy of Fallot. AB - Coexistence of divided left atrium with tetralogy of Fallot is rare. Preoperative diagnosis of this rare association is difficult. We here report preoperative diagnosis of this rare combination. In addition, the patient also had coronary to left ventricle fistula. PMID- 21976889 TI - A case of tetralogy of Fallot associated with left anterior descending coronary artery to pulmonary artery fistula. AB - Presence of coronary to pulmonary artery fistula is generally a feature of pulmonary atresia with ventricular septal defect. We present a rare case of left anterior descending coronary artery to pulmonary artery fistula in a patient of tetralogy of Fallot. PMID- 21976890 TI - Hutchinson-Gilford progeria syndrome with severe calcific aortic valve stenosis. AB - Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging syndrome that results from mutation in the Laminin A gene. This case report of a 12-year old girl with HGPS is presented for the rarity of the syndrome and the classical clinical features that were observed in the patient. All patients with this condition should undergo early and periodic evaluation for cardiovascular diseases. However, the prognosis is poor and management is mainly conservative. There is no proven therapy available. Mortality in this uniformly fatal condition is primarily due to myocardial infarction, strokes or congestive cardiac failure between ages 7 and 21 years due to the rapidly progressive arteriosclerosis involving the large vessels. PMID- 21976891 TI - Vitamin D deficiency presenting with cardiogenic shock in an infant. AB - A 2-month-old child was referred as a case of dilated cardiomyopathy with cardiogenic shock. On evaluation, hypocalcemia secondary to severe vitamin D deficiency was found. There were no clinical or radiological features of rickets. The child had developed multiorgan failure due to cardiogenic shock at the time of admission and could not be saved despite adequate ventilatory and pharmacologic support. Hypocalcemia should be considered as an important differential diagnosis in cases of dilated cardiomyopathy in infants. PMID- 21976892 TI - Kingella kingae endocarditis: A rare case of mitral valve perforation. AB - Kingella kingae, a HACEK (Haemophilus parainfluenzae, Aggregatibacter actinomycetemcomitans, Aggregatibacter aphrophilus, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae) organism, is a common resident of the upper airway in children; it has been associated with endocarditis in children with pre existing heart conditions. This case report describes K. kingae endocarditis leading to valvular damage in a previously healthy 18-month-old child. Our patient developed a K. kingae bacteremia that was later complicated by meningitis, septic embolic stroke, and endocarditis of the mitral valve, leading to perforation of the posterolateral leaflet. The patient was initially treated conservatively with cefotaxime but, subsequently, required a mitral valve repair with a pericardial patch and annuloplasty. This report draws attention to the need for clinicians to be aware of the potentially serious complications of K. kingae infection in young children. If K. kingae infection is suspected then therapy should be initiated promptly with a beta-lactam, followed by early echocardiographic assessment. This case also highlights the lack of specific guidelines available for K. kingae endocarditis. PMID- 21976893 TI - Supravalvular aortic stenosis in William's syndrome. AB - We report supravalvular aortic stenosis in a 12 year old patient who presented with mental retardation, malformed teeth, broad lower lips, pectus carinatum, clinodactyly, kyphoscoliosis with symptoms of shortness of breath. On examination presence of better volume pulse in right radial artery with ejection systolic murmur best heard in right 2(nd) intercostal space were noted. Patient was diagnosed as having William's syndrome with investigations demonstrating Supravalvular aortic stenosis with a gradient of 170 mm Hg. PMID- 21976894 TI - "Treatable" diffuse pulmonary arteriovenous fistula - An unusual cause. AB - A 4 year old boy was referred for evaluation of failure to thrive and mild cyanosis. He was found to have a structurally normal heart with evidence of microscopic pulmonary arterio-venous (AV) fistulae. Later, he was diagnosed to have congenital porto-systemic shunt, a very rare cause of pulmonary AV fistula. PMID- 21976895 TI - Unique echocardiographic features of mitral regurgitation associated with noncompaction of the ventricular myocardium. PMID- 21976896 TI - Largest ASD device closure. PMID- 21976898 TI - Cutaneous and aesthetic surgery in the new millennium. PMID- 21976899 TI - A review of surgical methods (excluding hair transplantation) and their role in hair loss management today. AB - There is more than one way to manage hair loss surgically. Apart from hair transplantation, there are other techniques which have been used by many to treat baldness. This article attempts to review the surgical methodology and philosophy that have acted as guiding lights in the approach to surgical treatment of baldness over the years and reviews the current role of other techniques in the armamentarium of hair restoration surgeons today. PMID- 21976900 TI - A Study on the Alterations in Skin Viscoelasticity before and after an Intradermal Administration of Growth Factor. AB - BACKGROUND: While photo-aging is believed to be preventable by the complete blockage of ultraviolet rays, there is no epoch-making method except sing fillers or autologous fat injection, for rejuvenating the skin once it has aged. OBJECTIVE: Our group developed a new method for rejuvenating aged skin by the direct intradermal injection of basic fibroblast growth factor, the first method of its kind in the world. In this paper we report the results of long-term follow up observations and alterations in skin viscoelasticity before and after this treatment. MATERIALS AND METHODS: A single dose of growth factor was injected directly into aged skin of the dorsal surface of the hand intradermally. The skin viscoelasticity of 50 treated cases was measured by a cutometer just before the treatment and at 1, 3, 6, and 9 months after treatment, respectively. RESULTS: WE OBSERVED THE FOLLOWING REJUVENATING EFFECTS: improved skin softness, gradual improvement of turgor, improved thickness of atrophied skin, and greatly improved viscoelasticity which reveals the improvement of biomechanical properties of the treated aged skin. According to the comparisons of viscoelasticity between pre- and post-treatment, the rejuvenated changes of R2 and R7 values were comparable to an age difference of more than 20 years. CONCLUSION: This method was confirmed to have excellent effects in rejuvenating aged skin safely and reliably including biomechanical properties. With this advance, we expect conventional non physiological skin rejuvenating treatments to be replaced by a much more fundamental method using one-time injections of the growth factor. PMID- 21976901 TI - Structural changes of fat tissue after nonaspirative ultrasonic hydrolipoclasy. AB - BACKGROUND: Hydrolipoclasy is an alternative technique less invasive than liposuction. Hydrolipoclasy uses normal saline or hypotonic solution and ultrasound waves that act directly on local adiposity. In the literature there are few reports of morphostructural changes on adipose tissue. MATERIALS AND METHODS: This study was aimed to evaluate the amount of fat cells injured immediately after treatment and after three days and also cell migration to the area treated using 8 pigs as experimental models, as well as cellular changes by transmission electron microscopy (TEM). RESULTS: The Wilcoxon test was conducted, and a difference was found between the treated side and the corresponding control side on the number of viable cells. The treated side showed a smaller number of viable cells compared to the control side both immediately after treatment and 3 days later. Also occurring 3 days after treatment was the migration of lymphoid cells and fibroblasts, which shows the local inflammatory process and conjunctive neoformation. Soon after treatment there was fluid accumulation within adipocytes. CONCLUSIONS: The results shown in this paper demonstrate Ultrasonic Hydrolipoclasy as a viable alternative for the treatment of localized fat deposits without the side effects of traditional surgical procedures. Better results are expected when hypotonic solution is used, since it penetrates into the cell. PMID- 21976902 TI - Maspin expression in epithelial skin tumours: an immunohistochemical study. AB - BACKGROUND: Maspin is a member of the serpin family of protease inhibitors and is thought to inhibit carcinoma invasion, metastasis, angiogenesis and induce apoptosis. AIM: The aim of this work is to investigate maspin expression in cutaneous basal and squamous cell carcinomas by means of immunohistochemistry. MATERIALS AND METHODS: This study was carried out on 43 patients, 25 basal cell carcinoma (BCC) and 18 squamous cell carcinoma (SCC) together with ten apparently healthy volunteers as a control group. RESULTS: There was a significant difference between the malignant and control groups regarding maspin expression since all control cases showed maspin expression compared to 60.5% (26/43) positivity in malignant cases. Maspin positive expression tended to be of higher percentage in SCC (77.8%) compared to BCC (48%) (P = 0.06) and the strong intensity of maspin was also significantly in favour of SCC compared to BCC (P = 0.02). The staining of both the cytoplasm and nuclei was seen in 27.7% of SCC and 12% of BCC and was significantly in favour of older age group (P = 0.02) and the adenoid variant (P = 0.04) of the latter. CONCLUSIONS: Maspin is associated with terminal squamous differentiation. Nuclear staining of maspin is seen in both BCC and SCC with a suggested tumour suppressor role in BCC. PMID- 21976903 TI - Sheares' method of vaginoplasty - our experience. AB - INTRODUCTION: The Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is one of the most common causes of primary amenorrhoea and is associated with vaginal atresia and absent uterus despite the presence of normal ovaries and external genitalia. Various techniques have been used, with many disadvantages, to create a neovagina. AIMS AND OBJECTIVES: Our aim is to create a neovagina with a simple and safe method. MATERIALS AND METHODS: We have operated 18 cases of MRKH syndrome with the Sheares' method of vaginoplasty, in which the space between the two labia is dilated with a Hegar's dilator along the vestigial Mullerian ducts. Thus, two tunnels are created and the central septum is excised to form a single vagina. A mould covered with amnion is placed in the neovagina. All cases are followed up for six months. They have all had a good length of vagina with regular manual dilatation. CONCLUSIONS: The Sheares' method of vaginoplasty is an easy and safe method to create a neovagina with least complications, like injury to urinary bladder, rectum or bleeding. PMID- 21976905 TI - Insects are Crawling in My Genital Warts. AB - A 23-year-old woman presented with large exophytic genital wart arising from perineum, vulva, introitus of the vagina, and inner aspect of thighs. Patient developed severe itching and formication (insect-crawling sensation) in the lesions for past 1 week, though careful examination did not reveal any insects. Considering that the disease was causing psychological stress and physical symptoms, radiofrequency excision was planned. However, during the procedure, several maggots appeared from the crypts. The procedure was abandoned and maggots were removed manually. Subsequently external giant warts were removed using radiofrequency device. There was no recurrence of excised warts during 3 month follow-up. To our knowledge, this is the second reported case of maggots in genital warts. PMID- 21976904 TI - Evaluation of Tissue Tightening by the Subdermal Nd: YAG Laser-Assisted Liposuction Versus Liposuction Alone. AB - BACKGROUND: Skin tightening is a desirable outcome for skin flaccidity. OBJECTIVE: We evaluated the applicability, safety, capacity and intensity of skin tightening with the subdermal 1,064 nm Nd: YAG laser application to the upper arms, and compared the results with liposuction. MATERIALS AND METHODS: Patients with lipodystrophy and mild-to-severe skin laxity of the arms were included (n=28). In half of patients, a single treatment with a subcutaneous laser and liposuction was performed, while the other 14 had a regular liposuction. Treatment parameters, adverse effects and photographic documentation were recorded. RESULTS: Aesthetic improvement and skin retraction was superior by laser lipolysis. The procedure was well tolerated without significant complications. CONCLUSIONS: The subdermal laser-assisted liposuction using a 1,064 nm Nd: YAG laser achieves improved skin tightening. PMID- 21976906 TI - Subcutaneous granular cell tumour of the lumbar region. AB - Granular cell tumour (GCT), also known as Abrikossoff tumour, is an uncommon neoplasm, probably of neural origin derived from Schwann cells. It usually presents as a subcutaneous solitary asymptomatic nodule. It has been the subject of much debate in the literature concerning the tumour origin and the association with other malignancies. We report a case of subcutaneous GCT in the lumbar region in a 31-year-old Caucasian male. Although they are a rare entity, GCTs should be considered in the differential diagnosis of the subcutaneous soft tissue tumours. Surgical removal with wide margins is the treatment of choice as malignant changes have been reported after long-term follow-up. PMID- 21976907 TI - Treatment of lipoma by injection lipolysis. AB - Injection lipolysis or lipodissolve is the practice of injecting phosphatidyl choline/ sodium deoxycholate (PDC/DC) compounds in the subcutaneous fat. Though this practice is being used extensively for nonsurgical contouring of body and dissolving localized collections of excess fat, it's use as a treatment modality for lipomas needs further evaluation. We present a case where this technique was used for treating a lipoma, with no recurrence after 9 months of follow up. Injection lipolysis as a treatment modality for lipomas needs to be evaluated for safety and efficacy in trials on larger population. This could prove to be a very valuable adjunct to the current practice of excision, if done by a trained person in a properly selected patient. Also the side effects and the controversies regarding this procedure have been discussed in detail in the present paper. PMID- 21976908 TI - Conchal defect correction by hinge flap and transposition flap. AB - Reconstruction of old full-thickness conchal defects is rarely described in the literature. This article describes a simple technique for reconstruction of old through-and-through small defects of the concha. The anterior part of the defect is covered with hinge flap taken from the posterior surface of the ear. The resultant final posterior defect is covered with local transposition flap from the adjacent skin. PMID- 21976909 TI - Massive abdominal wall endometriosis masquerading as desmoid tumour. AB - Endometriosis is a common gynaecological condition that usually presents as an abdominal lump. It can be a diagnostic dilemma and should be considered as a differential diagnosis for lumps in the abdomen in females. We discuss a case of abdominal wall endometriosis following caesarean section, which was misdiagnosed as a desmoid tumour. PMID- 21976910 TI - Laser: a powerful tool for treatment of pyogenic granuloma. AB - Lasers have opened a new door for the treatment of various disorders. Treatment of soft tissue intraoral mucosal growth by laser has profound effect on the patient acceptability taking the functional and aesthetic factor into consideration. The patient is able to get the outdoor treatment without the phobia of local anaesthetic and is out of the clinic in few minutes in contrast to the traditional method of surgical excision. Very few cases have been reported in literature regarding treatment of mucosal growth by soft tissue lasers. We present a case of recurrent pyogenic granuloma in a patient treated with an alternative approach, that is, diode laser, without the use of anaesthesia, sutures, anti-inflammatory drugs, or analgesics. The diagnosis of this lesion is equally important for correct treatment planning. PMID- 21976911 TI - 'Switch flap' for full thickness upper eyelid reconstruction. AB - Sebaceous gland carcinoma is an aggressive, uncommon, cutaneous malignancy. This tumour can arise anywhere in the body; approximately 75% of these tumours arise in the periocular region. The diagnosis and management of these malignancies often tend to get delayed because they are frequently mistaken for more common benign entities. Surgery has been and remains the primary treatment modality for sebaceous gland carcinomas. The resultant surgical defects following tumour excision generally tend to be full thickness and reconstructions of such defects pose significant challenges. These defects are conventionally reconstructed by the traditional bridging (eyelid sharing) procedures, that is, the Cutler-Beard flap and its modifications. The 'Switch flap' is an alternative eyelid sharing procedure; however, it is not very widely practiced. We recently used this procedure to reconstruct a large full-thickness upper eyelid defect with a satisfactory cosmetic and functional outcome. PMID- 21976912 TI - Recurrent adult nasal dermoid cyst. PMID- 21976913 TI - Intramuscular lipoma of tongue. PMID- 21976914 TI - Eccrine hidrocystoma successfully treated with topical synthetic botulinum Peptide. PMID- 21976915 TI - Female genital cosmetic surgery. PMID- 21976916 TI - Recurrent granuloma faciale successfully treated with the carbon dioxide laser. PMID- 21976917 TI - Cutaneous ciliated cyst over knee. PMID- 21976918 TI - CROSS Technique with Full Strength TCA in the Management of Ice Pick Acne Scars. PMID- 21976919 TI - Author's Reply. PMID- 21976920 TI - Sacral nevus lipomatosus cutaneous superficialis. PMID- 21976921 TI - The Genetic Equidistance Result of Molecular Evolution is Independent of Mutation Rates. AB - The well-established genetic equidistance result shows that sister species are approximately equidistant to a simpler outgroup as measured by DNA or protein dissimilarity. The equidistance result is the most direct evidence, and remains the only evidence, for the constant mutation rate interpretation of this result, known as the molecular clock. However, data independent of the equidistance result have steadily accumulated in recent years that often violate a constant mutation rate. Many have automatically inferred non-equidistance whenever a non constant mutation rate was observed, based on the unproven assumption that the equidistance result is an outcome of constant mutation rate. Here it is shown that the equidistance result remains valid even when different species can be independently shown to have different mutation rates. A random sampling of 50 proteins shows that nearly all proteins display the equidistance result despite the fact that many proteins have non-constant mutation rates. Therefore, the genetic equidistance result does not necessarily mean a constant mutation rate. Observations of different mutation rates do not invalidate the genetic equidistance result. New ideas are needed to explain the genetic equidistance result that must grant different mutation rates to different species and must be independently testable. PMID- 21976922 TI - Partial orchiectomy and testis intratubular germ cell neoplasia: World literature review. AB - Approximately 5% of all patients diagnosed with testicular cancer may have contralateral intratubular germ cell neoplasia (ITGCN) and may develop contralateral germ cell tumor. Here, we present a historical review and current literature regarding ITGCN and partial orchiectomy. The PubMed world literature search was performed for articles written in the English language. Search terms used were: Partial orchiectomy and ITGCN, with a return of 322 articles. Articles obtained were from the United States, Germany, Denmark and the Netherlands as well as a few case reports from Australia, France, Turkey and Spain. A critical review of the literature was performed. Partial orchiectomy is an option for the management of testicular malignancy in a select group of patients in whom radical orchiectomy is not desirable, including those with a solitary testicle, bilateral concurrent malignancies and a desire for paternity or being independent from androgen supplementation. Reports have demonstrated the feasibility of partial orchiectomy, but there are strict surgical criteria; tumor less than 2 cm in size, maintenance of cold ischemia, meticulous dissection to maintain testicular blood supply and biopsying of adjacent testicular parenchyma to ensure negative margins and absence of concurrent ITGCN. Partial orchiectomy is followed by testicular irradiation of 18-20 Gy; this radiation dose reduces fertility but maintains leydig cell function with androgen independence. Patients with a history of testicular carcinoma have a 5% chance of developing a metachronous contralateral tumor. Partial orchiectomy is a technically challenging procedure that requires close follow-up, but may represent a reasonable management option in selected patients. PMID- 21976923 TI - Long-term prognostic value of the combination of EORTC risk group calculator and molecular markers in non-muscle-invasive bladder cancer patients treated with intravesical Bacille Calmette-Guerin. AB - BACKGROUND AND OBJECTIVES: To evaluate the long-term prognostic value of the combination of the EORTC risk calculator and proapoptotic, antiapoptotic, proliferation, and invasiveness molecular markers in predicting the outcome of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) treated with intravesical Bacille Calmette-Guerin (BCG) therapy. MATERIALS AND METHODS: This study included 42 patients accrued prospectively presenting with intermediate- to high-risk NMIBC (high-grade T1 tumors or multiple rapidly recurrent tumors refractory to intravesical chemotherapy) treated with transurethral resection (TUR) and BCG. TUR samples were analyzed for the molecular markers p53, p21 waf1/cip, Bcl-2, CyclinD1, and metallothionein 9 (MMP9) using immunohistochemistry. Frequency of positivity, measured as a percentage, was assessed alone or in combination with EORTC risk calculator, for interaction with outcome in terms of recurrence and progression using univariate analysis and Kaplan-Meier survival curves. RESULTS: Median follow-up was 88 months (mean, 99; range, 14-212 months). The overall recurrence rate was 61.9% and progression rate was 21.4%. In univariate analysis, CyclinD1 and EORTC risk groups were significantly associated with recurrence (P value 0.03 and 0.02, respectively), although none of the markers showed a correlation to progression. In combining EORTC risk groups to markers expression status, high-risk group associated with positive MMP9, Bcl-2, CyclinD1, or p21 was significantly correlated to tumor recurrence (log rank P values <0.001, 0.03, 0.02, and 0.006, respectively) and when associated with positive MMP9 or p21, it was significantly correlated to progression (log rank P values 0.01 and 0.04, respectively). CONCLUSION: Molecular markers have a long-term prognostic value when combined with EORTC scoring system and they may be used to improve the predictive accuracy of currently existing scoring system. Larger series are needed to confirm these findings. PMID- 21976924 TI - Survival after primary and deferred cystectomy for stage T1 transitional cell carcinoma of the bladder. AB - CONTEXT: The optimal time of cystectomy for nonmuscle invasive bladder cancer (NMIBC) is controversial. AIM: This study aims at comparing cancer-specific survival in primary versus deferred cystectomy for T1 bladder cancer. SETTINGS AND DESIGN: Between 1990 and 2004, a retrospective cohort of 204 patients was studied. MATERIALS AND METHODS: Primary cystectomy at the diagnosis of NMIBC was performed in 134 patients (group 1) and deferred cystectomy was done after failed conservative treatment in 70 (group 2) Both groups were compared regarding patient and tumor characteristics and cancer-specific survival. STATISTICAL ANALYSIS USED: Cancer-specific survival was calculated using the Kaplan-Meier method. RESULTS: Mean follow-up was 79 and 66 months, respectively, in the two groups. Tumor multiplicity was more frequent in group 2; otherwise, both groups were comparable in all characteristics. The definitive stage was T1 in all patients. Although the 3-year (84% in group 1 vs. 79% in group 2), 5-year (78% vs. 71%) and 10-year (69% vs. 64%) cancer-specific survival rates were lower in the deferred cystectomy group, the difference was not statistically significant. In group 2, survival was significantly lower in cases undergoing more than three transurethral resections of bladder tumors (TURBT) than in cases with fewer TURBTs. CONCLUSIONS: Cancer-specific survival is statistically comparable for primary and deferred cystectomy in T1 bladder cancer, although there is a non significant difference in favor of primary cystectomy. In the deferred cystectomy group, the number of TURBTs beyond three is associated with lower survival. Conservative treatment should be adopted for most cases in this category. PMID- 21976925 TI - The new Olympus digital flexible ureteroscope (URF-V): Initial experience. AB - OBJECTIVE: Flexible ureterorenoscopes (FURSs) are considered important additions to urology armamentarium. One of the technical drawbacks is the poor optic image provided by fiberoptic endoscope as well as the fragility of this conventional fiberoptic endoscope. This study aim is to evaluate practical performances and functional durability of the new Olympus digital flexible ureteroscope (ODF-URS) (URF-V) in a single center clinical setting. MATERIALS AND METHODS: A number of 60 diagnostic and therapeutic procedures were performed over a period of 6 months in a single center (Tenon University Hospital), using a single ODF-URS (URF-V). This device provided a 275 degrees maximal down-deflection (MDD) and 180 degrees maximal up-deflection (MUD). RESULTS: ODF-URS (URF-V) was used for a total time of 90 h and 30 min, with average time duration of 90.5 min per procedure. After 60 procedures, MDD decreased from 275 degrees to 217 degrees , while the MUD decreased from 180 degrees to 161 degrees . During six procedures (10%), URF-V failed to access inferior calyx due to a narrow lower calyx infundibulum. CONCLUSION: New ODF-URS (URF-V) is a reliable and durable device, with a good success rate and improved functional parameters. It is a superior device compared to predecessor generations of conventional fiberoptic endoscopes for the light source and the image quality; however, randomized comparative studies are necessary to evaluate performances and durability of this device. PMID- 21976926 TI - Role of parenteral testosterone in hypospadias: A study from a teaching hospital in India. AB - OBJECTIVES: To evaluate the effect of parenteral testosterone on penile length, preputial skin and side effects in patients with hypospadias. MATERIALS AND METHODS: 23 patients with hypospadias were included in this study. An oily solution, each ml of which contained testosterone propionate 25 mg, and testosterone enanthate 110 mg, equivalent to 100 mg of testosterone was given deep intramuscularly 4, 3 and 2 weeks before reconstructive surgery at the dose of 2 mg/kg body weight. Increase in penile length, transverse preputial diameter, and diameter at the base of penis were noted. Basal testosterone levels were obtained before the institution of therapy and on the day of operation. In addition, side effect such as development of pubic hair and delay in bone age was noted. RESULTS: Following parenteral testosterone administration, the mean increase in penile length, transverse preputial diameter and diameter at the base of penis was 1.35+/-0.40 cm (P<0.001), 1.40+/-0.47 cm (P<0.001), and 0.72+/-0.47 cm (P<0.001), respectively. Serum testosterone level after injection was well within normal range for that age. Minimal side effects were noted in form of development of fine pubic hair. CONCLUSION: We conclude that parenteral testosterone can be safely used to improve the surgical outcome of hypospadias repair. PMID- 21976927 TI - Histomorphometric and sympathetic innervation of the human renal artery: A cadaveric study. AB - BACKGROUND AND AIM: Renal artery stenosis (RAS) and acute renal failure may be due to the intimal hyperplasia and sympathetic fibers of the renal artery (RA), respectively. The purpose of this study was to characterize arterial wall and sympathetic innervation of the human RA. MATERIALS AND METHODS: Fifty-two fresh human RA samples (proximal part) were collected from 26 cadavers (19 males and 7 females), between the ages of 19 and 83 years, during autopsy. Samples were divided into three age groups: Group 1, 19-40 years; Group 2, 41-60 years; Group 3, over 61 years. 5-MUm thick sections of each sample were taken and stained with hematoxylin-eosin and Verhoeff-Van Gieson. Five out of 52 samples were processed for tyrosine hydroxylase (TH) immunostaining. RESULTS: Our histological studies revealed that tunica media of RA showed smooth muscle cells and fine irregularly arranged elastic fibers. Intimal hyperplasia was the most common finding. The present study showed that thickness of tunica intima and media were found to increase with age. Sympathetic nerves were present in the tunica adventitia and outer media of the RA. The mean adventitial and sympathetic nerve fiber areas were found to be 0.595 and 0.071 mm(2), respectively. Sympathetic index (SI) to RA was calculated by dividing the sympathetic fiber area by the adventitial area of the RA. SI of RA was found to be 0.140. CONCLUSION: We conclude that RA showed the structure of musculo-elastic artery. SI may be used for the analysis of sympathetic fiber related problems of the human RA or kidneys. PMID- 21976928 TI - Rhabdomyolysis and myogloginuric acute renal failure in the lithotomy/exaggerated lithotomy position of urogenital surgeries. AB - OBJECTIVE: To evaluate rhabdomyolysis and it's management in lithotomy and the exaggerated lithotomy positions during urogenital surgeries. DESIGN: Retrospective study SETTING: Institute of Post Graduate Medical Education and Research (IPGME & R), Kolkata, India. MATERIALS AND METHODS: Patients undergoing urogenital surgeries (lithotomy and the exaggerated lithotomy positions). INTERVENTION(S): All four cases of rhabdomyolysis which occurred after such positional urogenital surgeries were treated with conservative management for prolonged period with hemodialysis. One case which developed compartment syndrome underwent fasciotomy and also managed with conservative approach as other cases. MAIN OUTCOME MEASURE: Rhabdomylysis is now a rare complication in any open or laparoscopic surgery. But prolonged lithotomy or exaggerated lithotomy position surgeries have been shown to expose patients to the risk of rhabdomylysis and acute renal failure. RESULTS: In our institute patients undergoing urogenital surgeries in lithotomy and the exaggerated lithotomy positions only developed rhabdomyolysis and myogloginuric acute renal failure. All procedures were of prolonged duration (mean five hours and ten minutes). Three patients developed rhabdomyolysis and acute renal failure without compartmental syndrome and one with compartmental syndrome. Rhabdomyolysis with the appearance of acute renal failure is discussed. CONCLUSION: Overall, our cases showed that rhabdomyolysis and acute renal failure can develop in such operative positions even in the absence of compartmental syndrome, and that duration of surgery is the most important risk factor for such complications. So we should be careful regarding duration of surgery in lithotomy procedure to prevent such morbid complications. PMID- 21976929 TI - Clear cell adenocarcinoma of urinary bladder: A case report and review. AB - Clear cell carcinoma is an uncommon but distinct variant of urinary bladder carcinoma histologically resembling the neoplasm in the female genital tract. The histogenesis of this neoplasm is uncertain. The clinicopathologic and histologic features are suggestive of a mullerian origin in some tumors, while some believe it to be glandular differentiation of urothelium or a unique vesicular adenocarcinoma of non-mullerian origin.[1] We present a case of clear cell adenocarcinoma in a 74-year-old woman with review of literature along with its differential diagnosis. PMID- 21976930 TI - Teratoid Wilms' tumor - A rare renal tumor. AB - Teratoid Wilms' tumor is an extremely rare renal tumor. We report a case of unilateral teratoid Wilms' tumor in a 4-year-old girl. The patient was admitted with a right-sided abdominal mass. The mass was arising from the right kidney. Radical nephrectomy was done and the patient had an uneventful recovery. Histopathology report showed teratoid Wilms' tumor. PMID- 21976931 TI - A case of solitary fibrous tumor of the kidney. AB - A solitary fibrous tumor (SFT) is an unusual spindle cell neoplasm that usually occurs in the pleura but has recently been described in diverse extrapleural sites. Urogenital localization is rare and to our knowledge, only 39 cases of SFT of the kidney have been described. Although SFT of the kidney is extremely rare, this tumor must be included in the differential diagnosis, whenever a renal tumor consisting of mesenchymal elements is encountered. We report a case of a large SFT of the right kidney which was clinically and radiologically thought to be renal cell carcinoma and a final diagnosis of SFT was made only after immunohistochemical study. PMID- 21976932 TI - Congenital penile urethrocutaneous fistula: A rare anomaly and review of literature. AB - Congenital penile urethrocutaneous fistula is described as an unusual developmental anomaly in children who present with an abnormal opening on the ventral aspect of penis with a normal foreskin and an absence of chordee and hypospadias. The authors present a discussion on the etiology, embryology, and management of this entity along with a description of three cases. We emphasize meticulous clinical examination for the diagnosis and to rule out other associated anomalies. PMID- 21976933 TI - Mucinous adenocarcinoma of the renal pelvis with adenocarcinoma in situ of the ureter. AB - Primary epithelial tumor of the renal pelvis is rare, and adenocarcinomas account for less than 1% of malignancies arising from the epithelium of the renal pelvis. We describe in this study a case of a 56-year old male patient who presented with an abdominal mass and dull aching pain for one year. A diagnosis of hydronephrosis of the right kidney was made based on imaging studies. Grossly, the entire kidney was converted into a cystic mass measuring 16 * 12 * 10 cm and filled with gelatinous material along with staghorn calculi in the pelvis measuring 7 * 4 * 3 cm. Histological examination of the tumor showed glands, cysts, and papillae lined by pseudostratified columnar epithelium with hyperchromatic nuclei. Scattered signet ring-type cells were also seen floating in large pools of extracellular mucin. Sections from the ureter showed a component of adenocarcinoma in situ. No invasive tumor was identified in ureteric tissue. Thus, a diagnosis of mucinous adenocarcinoma of the renal pelvis with in situ adenocarcinoma of the ureter was made. PMID- 21976934 TI - Dog bite injuries of genitalia in male infant and children. AB - The aim of the study is to highlight genital dog bites in male infant and children in developing countries and their management. We managed three cases (9 months, 5 years, and 8 years) of genital dog bite between January 1997 and July 2008. Two had unprovoked stray dog bites and the third was bitten by his pet dog when disturbed during eating. Extent of injury varied from small-lacerated wound to near emasculation. Primary repair was done after thorough washing and debridement under antibiotic cover. In the 9-month-old male infant who was near emasculated, scrotum was closed with the available skin and a small penile stump was reconstructed after meatoplasty. Immunization against tetanus and rabies was done for all cases. Postoperative recovery was uneventful, and the wound healed primarily in all cases. Parents of the infant were asked for feminizing genitoplasty but they refused so they were advised for hormonal replacement and penile reconstruction at adolescence. Male children are the most common victims of genital dog bites. These injuries can be repaired primarily with good outcome provided strict cleaning, debridement, wound repair, antibiotic cover, and immunization is applied. PMID- 21976935 TI - Intravitreal bevacizumab alone versus combined with macular photocoagulation in diabetic macular edema. AB - PURPOSE: To compare the efficacy between intravitreal bevacizumab and combination treatment (bevacizumab and macular photocoagulation) for the treatment of diabetic macular edema (DME). In addtion, changes of DME type were researched using optical coherence tomography. METHODS: The present study included 90 eyes with bevacizumab injection and 38 eyes with combination treatment. Using chart records, patients were reviewed until 6 months after treatment. The present study compared changes of visual acuity (VA) and macular thickness at each follow up. DME was classified into 4 types and the morphologic pattern was compared. RESULTS: In patients with the bevacizumab injection only, VA improved from 0.29 +/- 0.18 to 0.48 +/- 0.26 at 1 month and returned to 0.32 +/- 0.20 at 6 months after treatment. In the combination treatment, VA improved from 0.32 +/- 0.22 to 0.52 +/- 0.26 at 1 month and returned to 0.36 +/- 0.18 at 6 months after treatment. There was no significant improvement of VA at the final follow-up with either treatment. There was significant decrease of macular thickness except in the mixed DME type. CONCLUSIONS: The combination treatment did not yield better VA or macular thickness reduction at 6 months than bevacizumab injection alone. By classifying and observing the change of DME type, determining the treatment objectively and predicting the effectiveness of treatment can be helpful. PMID- 21976936 TI - Long-term results of lens-sparing vitrectomy for stages 4B and 5 retinopathy of prematurity. AB - PURPOSE: To assess long-term anatomic and visual outcomes and associated complications of lens-sparing vitrectomy (LSV) for treatment of tractional retinal detachments (TRDs) associated with stages 4B and 5 retinopathy of prematurity (ROP). METHODS: We performed a retrospective review of medical records and data analyses of consecutive patients who presented with stages 4B and 5 ROP and underwent LSV from 1999 to 2007. Retinal reattachment status, visual acuity and postoperative complications were evaluated. RESULTS: Twenty-one eyes of 20 patients, including 13 eyes with stage 4B ROP and 8 eyes with stage 5 ROP, were examined. The mean follow-up period was 5.6 years. In 9 (43%) out of 21 eyes, retinas were eventually reattached. The anatomic success rates were 62% in stage 4B and 13% in stage 5 ROP. In eyes with reattached retinas, visual acuity better than form vision was shown in 7 eyes (78%), whereas no light perception was present in 10 eyes (83%) among eyes with TRD on final examination. Postoperative intraocular hemorrhage occurred in nine eyes (43%). Long-term complications of cataract, corneal opacity, glaucoma and strabismus developed in 4 (19%), 6 (29%), 7 (33%) and 8 (38%) eyes, respectively, and were more common in eyes with TRD. CONCLUSIONS: After following-up for a mean of 5.6 years, the anatomical success rate of LSV was encouraging for the correction of TRD associated with stage 4B ROP but not for stage 5 ROP. Retinal reattachment is important for obtaining better visual outcomes and preventing the development of late complications. PMID- 21976937 TI - Retinal hemorrhage associated with perinatal distress in newborns. AB - PURPOSE: To describe the ophthalmoscopic features and natural history in a case series of eyes that developed intraocular hemorrhages associated with perinatal distress and to evaluate their clinical courses. METHODS: A retrospective chart review of 289 neonates with a medical history of perinatal distress was conducted. Among these 289 patients (578 eyes), 29 eyes of 17 neonates were found to have had retinal hemorrhages or vitreous hemorrhages (VH). A comprehensive chart review, including details of fundoscopic findings and perinatal history, was conducted. RESULTS: Intraocular hemorrhage was present in 5.5% of the patients. Most hemorrhages (82.7%) were intraretinal. In our population, 17% (n = 5) of hemorrhages resolved within two weeks, but 31% (n = 9) did not resolve even after four weeks. Most hemorrhages spontaneously resolved without any specific sequelae; however, one infant's dense unilateral VH persisted up to three months after birth. When the patient was seen again at 3.5 years of age, she had developed axial myopia and severe amblyopia of the involved eye. CONCLUSIONS: In asphyxiated newborns, the possibility of intraocular hemorrhages should be considered. Long-standing, dense hemorrhages obscuring the macula may lead to severe vision deprivation amblyopia. Therefore, ophthalmic examination should be considered in neonates with perinatal distress, and close observation is necessary for hemorrhages that do not resolve in this amblyogenic age group. PMID- 21976938 TI - Surgical outcomes of different Ahmed Glaucoma Valve implantation methods between scleral graft and scleral flap. AB - PURPOSE: To compare the surgical outcomes of the two different methods used for Ahmed Glaucoma Valve (AGV) implantation between the donor scleral graft method and the partial-thickness scleral flap method. METHODS: We retrospectively reviewed medical records of 28 eyes of 26 patients diagnosed as neovascular glaucoma followed by AGV implantation. Based on the surgical method, the included eyes were divided into two groups. In the graft group (n = 18), the drainage tube was inserted into the anterior chamber, and then covered with preserved donor sclera. In the flap group (n = 10), the drainage tube was inserted under the partial-thickness scleral flap, and then covered with the flap. We compared the postoperative intraocular pressure (IOP), surgical success rates, and postoperative complications between the two groups. RESULTS: Postoperative IOP was not significantly different between the two groups (p = 0.967, 0.495 at 12 months, 24 months, respectively, by the Mann-Whitney U-test). The mean success periods were 53.1 +/- 10.1 months in the graft group versus 50.9 +/- 9.4 months in the flap group (p = 0.882 by log rank test), and cumulative success rates were 77.8% and 80.0% at one year, respectively. However, tube migration occurred more frequently in the flap group than in the graft group (p = 0.037 by Fisher's exact test). CONCLUSIONS: In AGV surgery for neovascular glaucoma, the scleral graft method may be associated with relatively less complication about tube migration than the scleral flap method. The surgical results, however, were not statistically different. PMID- 21976939 TI - Short-term effects of Ginkgo biloba extract on peripapillary retinal blood flow in normal tension glaucoma. AB - PURPOSE: Based on the vascular theory of glaucoma pathogenesis, we wanted to evaluate the effect of Ginkgo biloba extract (GBE) on peripapillary blood flow in patients with normal tension glaucoma (NTG). METHODS: Thirty patients with NTG were randomly placed in the GBE-treated or control groups. The GBE-treated group received 80 mg GBE orally, twice a day for four weeks, and the control group received a placebo twice a day for four weeks. Complete ocular examinations including visual field, Heidelberg retina flowmeter, and systemic examinations were performed on the first study day and on the day treatment was completed. RESULTS: After GBE treatment, the mean blood flow, volume, and velocity increased at almost all points, and there was a statistically significant increase in blood flow at almost all points, in comparison to the placebo. Blood volume significantly increased only in the superior nasal and superior temporal neuroretinal rim areas. GBE also significantly increased blood velocity in areas of the inferior temporal neuroretinal rim and superior temporal peripapillary area. CONCLUSIONS: GBE administration appears to have desirable effect on ocular blood flow in NTG patients. PMID- 21976940 TI - Comparison of outcomes of unilateral lateral rectus recession for exotropia between first and second operations. AB - PURPOSE: To compare the outcomes of unilateral lateral rectus recession between the first operation and second operation for exotropia. METHODS: Thirty-two patients who underwent unilateral lateral rectus recession for exotropia of 15 to 20 prism diopters (PD) were investigated. The follow-up period was at least 6 months. We classified 17 patients without a surgical history for exotropia (first operation group) and 15 patients with a previous procedure (second operation group). Surgical success was defined as an exodeviation or esodeviation of less than 10 PD at the primary position. Postoperative deviation angles and success rates were compared between the two groups. RESULTS: There were no significant differences in the age, gender, visual acuity (logarithm of the minimal angle of resolution), preoperative deviation, and amount of recession between the two groups. Postoperative deviations were -1.7 +/- 5.5:1.3 +/- 5.1 PD at one day, 4.3 +/- 3.8:5.6 +/- 5.1 PD at 1 month, 4.3 +/- 4.3:3.0 +/- 8.1 PD at 3 months, and 5.0 +/- 4.3:4.5 +/- 7.2 PD at 6 months post-operation, and there was no statistically significant difference between the two study groups. Surgical success rate were 95.2:100% at one day, 95.2:92.9% at 1 month, 90.5:85.7% at 3 months, and 90.0:92.9% a 6 months post-operation. CONCLUSIONS: In patients with exotropia of 15 to 20 PD, no significant difference was found in terms of the postoperative deviation angle and the surgical success rate between the first operation and the second operation groups. Unilateral lateral rectus recession can lead to similar results in 15 to 20 PD exotropia for the first operation or recurrent exotropia. PMID- 21976941 TI - Study for analysis of the multifocal visual evoked potential. AB - PURPOSE: To introduce the clinical utility of the absolute value of the reconstructed waveform method in the analysis of multifocal visual evoked potential (mfVEP). METHODS: The mfVEP with 4-channel recording was performed using RETIscan(r) on 10 eyes of 10 normal subjects. Amplitudes were obtained from ring-shaped 6 areas and 4 sectors. The best visual evoked potential (VEP) response method and the absolute value of the reconstructed waveform method were compared in terms of analysis of the amplitudes. In order to assess the false positive rate of the examination, stimuli were administered with one-half of the cathode ray tube (CRT) monitor completely covered and the results were compared using 2 methods. RESULTS: The amplitudes in 6 areas and 4 sectors analyzed with the best VEP response method and the absolute value of the reconstructed waveform method showed no statistical difference (p > 0.05). The amplitude in the stimuli blocked area of the absolute value of the reconstructed waveform method was smaller than that of the best VEP response method (p < 0.05) and the amplitude of the stimuli area showed no substantial difference between two methods (p > 0.05). CONCLUSIONS: The absolute value of the reconstructed waveform method has similar reproducibility and lower level of false positives relative to the best VEP response method. Therefore, it can be considered as a useful method in the analysis of the mfVEP. PMID- 21976942 TI - Analysis of the effects of medial rectus muscle resection for recurrent exotropia. AB - PURPOSE: The purpose of this paper is to investigate how much correction is obtained per millimeter of medial rectus (MR) resection for recurrent exotropia after bilateral lateral rectus (BLR) recession, and to determine the difference in the effects between unilateral and bilateral resection, and the influence of previous lateral rectus (LR) recession on the effects of MR resection. METHODS: A total of 59 patients who had undergone MR resection after BLR recession were included in this study. The unilateral group consisted of 38 patients and bilateral group, 21 patients. Thirty patients in the unilateral group were divided into two groups: patients who had undergone previous LR recession of 7 mm or greater (21 patients) and less than 7 mm (9 patients). Main outcome measures were average deviation corrected per millimeter of MR resection at 1 month postoperative. RESULTS: The average effect of MR resection was 4.2 prism diopters (PD, 2.0 to 6.7 PD)/mm. The average effect in the unilateral group was 4.2 PD/mm and 4.1 PD/mm in the bilateral group. There was no significant difference between groups (P = 0.60). The average effect in the recession 7 mm or greater group was 4.0 PD/mm, and the average effect in the recession less than 7 mm group was 4.2 PD/mm (P = 0.698). CONCLUSIONS: The effect of MR resection per millimeter was variable. The laterality and previous amount of LR recession did not influence the effect of MR resection. These variable outcomes dictate that caution be exercised when MR resection is performed for recurrent exotropia. PMID- 21976943 TI - Microscopic characteristics of lower eyelid retractors in Koreans. AB - PURPOSE: To identify the microscopic characteristics of lower eyelid retractors in Korean individuals and to elucidate age-related changes in lower eyelid retractors. METHODS: Eighteen Korean lower eyelids from formalin-fixed cadavers were stained with Masson's trichrome. Specimens were divided into two groups based on age at death (group A, <=65 years; group B, >65 years), and the microscopic findings were analyzed and compared by light microscopy. RESULTS: The capsulopalpebral fascia (CPF) had distinct junctions and no fusion with orbital septum in 14 eyelids (77.8%). The CPF was fused with the orbital septum in only two eyelids (11.1%). Although not significant, the inferior tarsal muscle was closer to the tarsus in group A (1.24 +/- 0.71 mm) than group B (2.14 +/- 1.18 mm, p = 0.07), and the tarsal height tended to be longer in group B (4.71 +/- 0.55 mm) than group A (4.16 +/- 1.01 mm, p = 0.20). Tarsal fatty infiltration was more evident in group B. CONCLUSIONS: The CPF was rarely fused with the orbital septum in our sample of Korean lower eyelids. Although we did not identify any remarkable age-related changes in lower eyelid structures, there was a tendency for the lower retractor to loosen from the tarsus and for increased fatty infiltration in the lower eyelids from elderly individuals. PMID- 21976944 TI - A case of Stenotrophomonas maltophilia keratitis effectively treated with moxifloxacin. AB - A 70-year-old man with a long history of diabetes mellitus presented to our hospital (Department of Ophthalmology, Sahm Yook Medical Center, Seoul, Korea) complaining of severe ocular pain and visual disturbance in his left eye that had started three days prior to admission. A round 3.7 * 5.0 mm dense central stromal infiltrate with an overlying epithelial defect was noted on slit-lamp examination. Following corneal scrapings and culture, topical 0.5% moxifloxacin and 0.5% tobramycin were administered hourly. A few days later, Stenotrophomonas maltophilia was isolated in a bacterial culture from a corneal specimen. According to the results of susceptibility tests, topical 0.5% moxifloxacin was given every hour and 0.5% tobramycin was stopped. The patient's clinical features improved steadily with treatment. The corneal epithelium healed rapidly, and the infiltrate resolved within four weeks of the initiation of treatment. The patient's best corrected visual acuity improved from hand motion to 20 / 25. PMID- 21976945 TI - Unilateral Peters' anomaly with chorioretinal coloboma in the other eye. AB - An 18-year-old man presented with poor vision in both eyes that had been present since birth. Central corneal opacity and inferior peripheral sclerocornea with iridocorneal adhesion were observed upon anterior segment examination of the left eye. A coloboma of the iris was observed in the patient's right eye, which manifested as a small notch in the inferior pupillary margin and cataract. Fundus examination of the right eye showed a large inferior chorioretinal coloboma involving the optic disc and macula. It is essential to examine the fundus in detail, if possible, in cases of Peters' anomaly, because these patients may have congenital anomalies such as chorioretinal coloboma. PMID- 21976946 TI - Vortex keratopathy in a patient receiving vandetanib for non-small cell lung cancer. AB - We report a case of vortex keratopathy in a patient treated with vandetanib for non-small cell lung cancer (NSCLC). A 44-year-old female who underwent two cycles of chemotherapy for NSCLC complained of visual blurring in both eyes after the initiation of vandetanib, an anti-epidermal growth factor receptor (EGFR) and anti-vascular endothelial growth factor receptor 2 protein tyrosine kinase inhibitor. On ophthalmic examination, visual acuities were 20 / 20 OU and, with the exception of diffuse vortex keratopathy in both eyes, other findings were unremarkable. Vandetanib is believed to have caused vortex keratopathy in this patient. Anti-EGFR properties affecting normal corneal epithelial cell migration and wound healing or drug associated metabolite deposition, which is the case in numerous drug-associated vortex keratopathies, may be possible underlying mechanisms in the formation of this corneal complication. PMID- 21976947 TI - Ophthalmic artery obstruction and cerebral infarction following periocular injection of autologous fat. AB - We report a case of ophthalmic artery obstruction combined with brain infarction following periocular autologous fat injection. The patient, a 44-year-old woman, visited our hospital for decreased visual acuity in her left eye and dysarthria one hour after receiving an autologous fat injection in the periocular area. Her best corrected visual acuity for the concerned eye was no light perception. Also, a relative afferent pupillary defect was detected in this eye. The left fundus exhibited widespread retinal whitening with visible emboli in several retinal arterioles. Diffusion-weighted magnetic resonance imaging of the brain showed a hyperintense lesion at the left insular cortex. Therefore, we diagnosed ophthalmic artery obstruction and left middle cerebral artery infarction due to fat emboli. The patient was managed with immediate ocular massage, carbon dioxide, and oxygen therapy. Following treatment, dysarthria improved considerably but there was no improvement in visual acuity. PMID- 21976948 TI - A case of cholesterosis bulbi with secondary glaucoma treated by vitrectomy and intravitreal bevacizumab. AB - We report on a case of cholesterosis bulbi concurrent with secondary glaucoma. A 36-year-old man, with a history of long-standing retinal detachment in his right eye after the irrigation and aspiration of a congenital cataract, presented with a clinical picture of elevated intraocular pressure and ocular pain. Upon slit lamp examination, we found a ciliary injection and a pseudohypopyon of polychromatic crystals. Gonioscopic examination revealed a large amount of crystals deposited on the trabecular meshwork and mild rubeosis iridis, but the neovascularization of the angle could not be clearly confirmed due to the presence of so many crystals. Pars plana vitrectomy was performed to remove clusters of crystals and bevacizumab was injected intravitreally to treat iris neovascularization. Aqueous aspirate was examined by light microscopy and the typical highly refringent cholesterol crystals were identified. Intraocular pressure returned to a normal level after the bevacizumab injection, although severe cholesterosis was still evident in the anterior chamber. To our knowledge, this would be the first Korean case of cholesterosis bulbi combined with chronic retinal detachment and presumed neovascular glaucoma, which was treated by pars plana vitrectomy and intravitreal bevacizumab injection. PMID- 21976949 TI - Computed tomographic angiogram of an anterior communicating artery aneurysm causing acute retrobulbar optic neuropathy: a case report. AB - Three-dimensional computed tomographic (3D-CT) angiography is a widespread imaging modality for intracranial vascular lesions. However, 3D-CT angiograms of an anterior communicating artery aneurysm associated with acute retrobulbar optic neuropathy have not been previously described. We present 3D-CT angiograms of an aneurysm of the anterior communicating artery that caused subarachnoid hemorrhage and vision loss in a 39-year old man. The 3D-CT angiograms were consistent with findings identified directly during surgery. PMID- 21976950 TI - Learning curve in a Western training center of the circumferential en bloc esophageal endoscopic submucosal dissection in an in vivo animal model. AB - Aim. Evaluate the feasibility to overcome the learning curve in a western training center of the en bloc circumferential esophageal (ECE-) ESD in an in vivo animal model. Methods. ECE-ESD was performed on ten canine models under general anesthesia on artificial lesions at the esophagus marked with coagulation points. After the ESD each canine model was euthanized and surgical resection of the esophagus and stomach was carried out according to "the Principles of Humane Experimental Technique, Russel and Burch." The specimen was fixed with needles on cork submerged in formalin with the esophagus and stomach then delivered to the pathology department to be analyzed. Results. ECE-ESD was completed without complications in the last 3/10 animal models. Mean duration for the procedures was 192 +/- 35 minutes (range 140-235 minutes). All the procedures were done at the animal lab surgery room with cardio pulmonary monitoring and artificial ventilation by staff surgery members and a staff member of the Gastroenterology department trained during 1999-2001 at the Fujigaoka hospital of the Showa U. in Yokohama, Japan, length (range 15-18 mm) and 51 +/- 6.99 width (range 40-60 mm). Conclusion. ECE-ESD training is feasible in canine models for postgraduate endoscopy fellows. PMID- 21976951 TI - IL-6 induction in desiccated corneal epithelium in vitro and in vivo. AB - PURPOSE: To investigate the effect of desiccation on secretion of inflammatory cytokines in corneal epithelial cells and in the rat desiccation model. METHODS: A human corneal epithelial cell line (CEPI) was grown in keratinocyte growth medium 2 (KGM2) to approximately 80% confluence. The medium was aspirated and dishes were left for 0 to 30 min with the cover left open to dry the cells (short term desiccation). After desiccation, KGM2 was added to the dishes and collected from the dishes 15 min later to measure the concentrations of cytokines in the medium by sandwich enzyme immunoassay (ELISA). Viability of the cells was estimated with alamer blue. To study the effect of long-term desiccation, cultivated cells on transwells were used. After dessiccation for up to 8 h, the viability of the cells and levels of cytokines in the culture medium were examined. The expression of cytokines in the cornea of the dry eye model rat was measured by real-time PCR. RESULTS: Short-term dessication of CEPI cells significantly increased the interleukin (IL)-6 level and slightly increased the tumor necrosis factor (TNF)-alpha level. Anti-IL-6 antibody partially suppressed cell death caused by desiccation. Upon long-term desiccation, IL-6 and IL-8 levels were increased. ?In the dry eye model rats, the IL-6 mRNA level in the cornea significantly increased, whereas TNF-alpha mRNA level slightly increased. CONCLUSIONS: Desiccation induced IL-6 expression in corneal epithelial cells, suggesting that IL-6 participates in desiccation-induced cell death. PMID- 21976952 TI - Structural and functional roles of deamidation of N146 and/or truncation of NH2- or COOH-termini in human alphaB-crystallin. AB - PURPOSE: The purpose of the study was to determine the relative effects of deamidation and/or truncation on the structural and functional properties of alphaB-crystallin. METHODS: Using wild-type (WT) alphaB-crystallin and the alphaB deamidated mutant (i.e., alphaB N146D), we generated NH(2)-terminal domain deleted (residues no. 1-66; alphaB-NT), deamidated plus NH(2)-terminal domain deleted (alphaB N146D-NT), COOH-terminal extension deleted (residues no. 151-175; alphaB-CT), and deamidated plus COOH-terminal extension deleted (alphaB N146D-CT) mutants. All of the proteins were purified and their structural and functional (chaperone activity with insulin as target protein) properties were determined and compared to WT alphaB-crystallin. RESULTS: The desired deletions in the alphaB-crystallin mutants were confirmed by DNA sequencing and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometric analysis. The homomers of alphaB-CT and its deamidated form (alphaB N146D-CT) became water insoluble, whereas the alphaB N146D, alphaB-NT, and alphaB N146D-NT species remained water-soluble. CD spectroscopic studies revealed that the mutants with deletion of NH(2)- or COOH-termini or deamidation showed increased beta-sheet and decreased alpha-helical contents with the exception of alphaB N146D-CT, which showed a substantial increase in alpha-helix and decrease in beta sheet content. Results of intrinsic Trp fluorescence suggested little change in Trp microenvironment of alphaB N146D relative to WT alphaB, but substantial alterations on deletion of COOH-terminal extension or a combination of this deletion plus deamidation. Hydrophobic binding studies using the hydrophobic probe 8-anilino-1-naphthalene sulfonate (ANS) showed that, relative to WT alphaB structure, the N146 deamidation, COOH-terminal extension deletion or a combination of this deamidation and deletion resulted in a relatively compact structure whereas the NH(2)-terminal domain deletion and a combination of this deletion plus deamidation resulted in a relaxed structure. All the alphaB mutants showed higher molecular mass ranging between 1.2*10(6) to 5.4*10(6) Da, relative to WT alphaB which had a molecular mass of 5.8*10(5) Da. Chaperone activity across all alphaB species decreased in the following order: WTalphaB > alphaB N146D-CT > alphaB N146D-NT > alphaB-NT > alphaB-CT > alphaB N146D. Specifically, substantial losses in chaperone activity (only 10% to 20% protection) were seen in alphaB N146D, alphaB-NT, and alphaB-CT. However, in the species with the combination of deamidation plus NH(2)- or COOH-terminal deletion, the percent protection was about 24% in alphaB N146D-NT and about 40% in alphaB N146D-CT. CONCLUSIONS: Although all mutants formed oligomers even after deamidation, on deletion of either NH(2)-terminal domain or COOH-terminal extension or a combination of these deletions and deamidation, their structural properties were substantially altered. The results suggested that the NH(2)-terminal domain is relatively more important than the COOH-terminal extension for the chaperone function of alphaB. The non-deamidated N146 residue, NH(2)-terminal domain and COOH-terminal extension are also of critical importance to the maintenance of alphaB-crystallin chaperone activity. PMID- 21976953 TI - Identification of a novel FBN1 gene mutation in a Chinese family with Marfan syndrome. AB - PURPOSE: To identify the mutation in the fibrillin-1 gene (FBN1) in a Chinese family with Marfan syndrome (MFS). METHODS: Patients and family members were given complete physical, ophthalmic, and cardiovascular examinations. Genomic DNA was extracted from leukocytes of venous blood of six individuals in the family and 170 healthy Chinese individuals. All of the 65 coding exons and their flanking intronic boundaries of FBN1 were amplified in the proband by polymerase chain reaction and followed by direct sequencing. The mutation identified in the proband was screened in the other family members and the 170 healthy Chinese individuals by direct sequencing. Protein conservation analysis was performed in six species using an online ClustalW tool. Protein structure was modeled based on the Protein data bank and mutated in DeepView v4.0.1 to predict the functional consequences of the mutation. RESULTS: A novel heterozygous c.3703T>C change in exon 29 of FBN1 was detected in the proband, which resulted in the substitution of serine by proline at codon 1235 (p.S1235P). This mutation was also present in two family members but absent in the other, unaffected family members and the 170 healthy Chinese individuals. The mutant residue located in the calcium binding epidermal growth factor-like#15 domain is highly conserved among mammalian species and could probably induce conformation change of the domain. CONCLUSIONS: We indentified a novel p.S1235P mutation in FBN1, which is the causative mutation for MFS in this family. Our result expands the mutation spectrum of FBN1 and contributes to the study of the molecular pathogenesis of Marfan syndrome. PMID- 21976954 TI - IGF-1 gene polymorphisms in Polish families with high-grade myopia. AB - PURPOSE: Recent work has suggested that insulin-like growth factor 1 (IGF-1) gene polymorphisms are genetically linked with high-grade myopia (HM), which is a complex-trait eye disorder in which numerous candidate loci and genes are thought to play a role. We investigated whether the IGF-1 single nucleotide polymorphisms (SNPs) rs6214, rs10860860, and rs2946834 are associated with HM (<=-6.0 diopters [D]) and any myopia (<=-0.5 D) phenotype in Polish families. METHODS: Forty-two multiplex HM Polish families, of whom 127 had HM, participated in the study. All of the family members (n=306) underwent a detailed ophthalmic examination, including axial length measurements. The IGF-1 SNPs rs6214, rs10860860, and rs2946834 were evaluated by PCR-RFLP and direct sequencing methods. Both Family Based Association Test (FBAT) and family-based Pedigree Disequilibrium Test (PDT) were used to examine the potential association of the IGF-1 SNPs rs6214, rs10860860, and rs2946834 with HM or any myopia. To determine the distribution of the HM-associated SNPs rs6214 and rs10860860, 543 unrelated individuals from the general Polish population were also analyzed. RESULTS: We found no significant association between the IGF-1 SNPs rs6214, rs10860860, and rs2946834 and HM or any myopia phenotype in Polish HM families. In the general Polish population, the minor allele frequencies of the SNPs rs6214 and rs10860860 did not deviate significantly from the distribution reported for European populations (p=0.629). In the FBAT analysis under the dominant model, the haplotype consisted of T allele of rs10860860, with C allele of rs2946834 of IGF-1 was found less frequently transmitted to HM individuals (p=0.0065), pointing to a nonassociated or protective haplotype. CONCLUSIONS: Our results do not support recent studies reporting an association of the SNPs rs6214, rs10860860, and rs2946834 in the IGF 1 gene with HM and any myopia phenotypes. Further replication studies involving other populations are needed to investigate the possible role of IGF-1 as a potential myopia candidate gene. PMID- 21976955 TI - The chicken cornea as a model of wound healing and neuronal re-innervation. AB - PURPOSE: The cornea is the major refractive component of the eye and serves as a barrier to the external environment. Understanding how the cornea responds to injury is important to developing therapies to treat vision disorders that affect the integrity and refractive properties of the cornea. Thus, investigation of the wound healing responses of the cornea to injury in a cost-effective animal model is a valuable tool for research. This study characterizes the wound healing responses in the corneas of White Leghorn chicken. METHODS: Linear corneal wounds were induced in post-natal day 7 (P7) chicks and cellular proliferation, apoptosis and regulation of structural proteins were assessed using immunohistochemical techniques. We describe the time course of increased expression of different scar-related markers, including vimentin, vinculin, perlecan and smooth muscle actin. RESULTS: We find evidence for acute necrotic cell death in the corneal region immediately surrounding cite of incision, whereas we failed to find evidence of delayed cell death or apoptosis. We find that the neuronal re-innervation of SV2-positive axon terminals within the corneal stroma and epithelium occurs very quickly after the initial scarring insult. We describe an accumulation of cells within the stroma immediately underlying the scar, which results, at least in part, from the local proliferation of keratocytes. Further, we provide evidence for scar-induced accumulations of CD45-positive monocytes in injured corneas. CONCLUSIONS: We conclude that the chick cornea is an excellent model system in which to study wound healing, formation of scar tissue, and neuronal re-innervation of sensory endings. PMID- 21976956 TI - Complex interactions of Tyrp1 in the eye. AB - PURPOSE: To use a systems genetics approach to construct and analyze co expression networks that are causally linked to mutations in a key pigementation gene, tyrosinase-related protein 1 (Tyrp1), that is associated both with oculocutaneous albinism type 3 (OCA3) in humans and with glaucoma in mice. METHODS: Gene expression patterns were measured in whole eyes of a large family of BXD recombinant inbred (RI) mice derived from parental lines that encode for wildtype (C57BL/6J) and mutant (DBA/2J) Tyrp1. Protein levels of Tyrp1 were measured in whole eyes and isolated irides. Bioinformatics analyses were performed on the expression data along with our archived sequence data. Separate data sets were generated which were comprised of strains that harbor either wildtype or mutant Tyrp1 and each was mined individually to identify gene networks that covary significantly with each isoform of Tyrp1. Ontology trees and network graphs were generated to probe essential function and statistical significance of covariation. Genes with strong covariance in wildtype mice were assembled into genome-wide heatmaps for cohorts carrying either wildtype or mutant Tyrp1. RESULTS: Single nucleotide polymorphism (SNP) analysis verified the presence of the Tyrp1b mutation in the Tyrp1 gene. Message levels were greater in BXD strains with the mutant Tyrp1. Interval mapping of these BXD mice revealed a strong expression quantitative trait locus (eQTL) on Chr 4 at the location of the gene itself. Composite mapping revealed a suggestive eQTL on Chr 9 at the location of myosin-Va (Myo5a), mutations in which are known as dilute. Enriched biologic processes associated with wildtype Tyrp1 included pigmentation, melanin biosynthetic process, and mesenchymal cell development, while associations with the mutant gene included categories of neural crest cell development, protein metabolic processes and glycoprotein metabolic processes. Genome-wide heatmaps revealed strong candidate cis-eQTLs on Chr 4 at Tyrp1 and on Chr 9 at Myo5a in all mice. In the wildtype data set, Tyrp1 was an upstream regulator of six pigmentation and two mesenchyme genes. In addition, five genes, including Tyrp1, were at least partially regulated by Myo5a. Analyses of the strains harboring the mutant gene revealed significant loss of correlation to traditional genes and gain of correlation to genes with little or no functional relationship. CONCLUSIONS: These findings indicate that the Tyrp1(b) mutation modifies the pathways and gene networks in which Tyrp1 functions. Our results also indicate direct and indirect regulatory control of Tyrp1 and other pigmentation and mesenchymal genes by Myo5a. Lastly, we find that the mutations reduce the ability of Tyrp1 to regulate expression of other genes that participate in pigmentation metabolism. PMID- 21976957 TI - CD40 polymorphisms in Han Chinese patients with Fuch uveitis syndrome. AB - PURPOSE: Polymorphisms of the cluster of differentiation 40 (CD40) gene have recently been identified to be associated with the risk to several immune diseases. The aim of this study was to determine the potential association of CD40 polymorphisms with Fuch uveitis syndrome (FUS). METHODS: A total of 131 Han Chinese patients with FUS and 402 healthy controls were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Genotype counts in patients and controls were analyzed by the chi(2) test. RESULTS: All genotypic and allelic frequencies of the tested two CD40 polymorphisms were in Hardy-Weinberg equilibrium. The genotypic and allelic frequencies of rs4810485 and rs1883832 were not different between patients with FUS and controls. No influence of sex could be found following stratification analysis according to gender. CONCLUSIONS: Our results suggest that the two investigated single-nucleotide polymorphisms (SNPs), rs4810485 and rs1883832, in CD40 are not associated with FUS in the Han Chinese population. PMID- 21976958 TI - SOD2 contributes to anti-oxidative capacity in rabbit corneal endothelial cells. AB - PURPOSE: Corneal endothelial cells are rich in mitochondria, a potential source of reactive oxygen species (ROS). ROS have been implicated in endothelial cell loss during aging or in endothelial dystrophies. In this study we examined the anti-oxidative role of mitochondrial superoxide dismutase (SOD2) in corneal endothelial cells. METHODS: SOD2 expression was examined by RT-PCR and western blot analysis in fresh rabbit corneal endothelium (RCE) and cell cultures. SOD2 activity, total reactive oxygen species (ROS), mitochondrial ROS, mitochondrial membrane potential (MMP), and apoptotic levels were examined in untreated, SOD2 siRNA and viral vector shRNA treated RCE cells. Scrambled siRNA and shRNA sequence targeting non-mammalian genes were used as controls. RESULTS: SOD2 is expressed in both fresh and cultured rabbit corneal endothelium. SOD2 expression was reduced by ~80%-90% in cultured RCE using either siRNA or shRNA approaches. SOD2 activity was decreased by ~70%-80% for both approaches. Total cell ROS was significantly increased in shSOD2 lentivirus treated cells (9%+/-6%) relative to control transduction (0.4%+/-0.1%). MitoSOXTM staining for mitochondrial ROS in siSOD2 treated RCE cells was dramatically increased. Two minutes of UV irradiation increased total ROS levels by 15%, whereas in shSOD2 treated cells UV induced ROS was increased 29%+/-5% (p<0.05). MMP was reduced in shSOD2 viral treated cells by 66%+/-3%, significantly greater than in control transduced cells (15%+/-8%, p<0.05). Apoptosis increased by 1.5 fold in shSOD2 virus treated samples compared with scrambled virus and untreated cells. CONCLUSIONS: SOD2 is expressed in both fresh and cultured rabbit corneal endothelium. siRNA and shRNA approaches are able to efficiently knockdown SOD2 expression and reduce enzyme activity in RCE cells. Decreased SOD2 activity causes elevated ROS production, mitochondrial membrane potential loss and early cell apoptosis. These results indicate that SOD2 is a significant anti-oxidative enzyme in RCE cells. PMID- 21976959 TI - Mutational screening of VSX1, SPARC, SOD1, LOX, and TIMP3 in keratoconus. AB - PURPOSE: To evaluate the involvement of Visual System Homeobox 1 (VSX1), Secreted Protein Acidic and Rich in Cysteine (SPARC), Superoxide Dismutase 1 (SOD1), Lysyl Oxidase (LOX), and Tissue Inhibitor of Metalloproteinase 3 (TIMP3) in sporadic and familial keratoconus. METHODS: Mutational analysis of the five genes was performed by sequencing and fragment analysis in a large cohort of 302 Italian patients, with a diagnosis of keratoconus based on clinical examination and corneal topography. The variants identified in VSX1 and SPARC were also assessed in the available relatives of the probands. RESULTS: A novel mutation p.G239R and previously reported mutations were found in VSX1. Novel and already reported variants were identified in SPARC and SOD1, whose pathogenic significance has not been established. No pathogenic variants have been identified in LOX and TIMP3. CONCLUSIONS: Molecular analysis of the five genes in a cohort of 225 sporadic and 77 familial keratoconus cases confirms the possible pathogenic role of VSX1 though in a small number of patients; a possible involvement of LOX and TIMP3 could be excluded; and the role played by SOD1 and SPARC in determining the disease as not been definitively clarified. Further studies are required to identify other important genetic factors involved in the pathogenesis and progression of the disease that in the authors' opinion, and according with several authors, should be considered as a complex disease. PMID- 21976960 TI - Anti-proliferation effects of Sirolimus sustained delivery film in rabbit glaucoma filtration surgery. AB - PURPOSE: To investigate the efficacy, safety, and mechanisms of Sirolimus sustained delivery film on prevention of scar formation in a rabbit model of glaucoma filtration surgery. METHODS: Sixty-four New Zealand white rabbits who underwent trabeculectomy in the right eye were randomly allocated to one of the four treatment regimens: Sirolimus sustained delivery film treatment group (Group A), or drug-free film treatment group (Group B), or 30 ng/ml Sirolimus-soaked sponge treatment group (Group C), or no adjunctive treatment group (Group D), and each group consists of 16 rabbits. Intraocular pressure (IOP), morphologic changes of bleb, anterior chamber flare, and corneal endothelial cell count and complications were evaluated over a 28-day period follow-up time. Aqueous humor samples were gathered from Group A, and the concentration of Sirolimus was measured regularly post-operation. Rabbits were sacrificed on the 7th, 14th, and 28th day post-operation separately, and the fibroblast hypertrophy, infiltration of inflammatory, and proliferation of new collagen fiber formation in each group were evaluated with HE and Masson staining. Proliferative cell nuclear antigen (PCNA) and fibroblast apoptosis were evaluated by immunohistochemistry and terminal deoxynucleotidyl transferasemediated dUTP nick end labeling (TUNEL) assay at the 28th day post-operation. RESULTS: Both Sirolimus sustained delivery film (Group A) and Sirolimus alone (Group C) were well tolerated in this model, and significantly prolonged bleb survival compared with no drug treatment group (Group B and D; p<0.001). Group A had the longest bleb survival time in comparison with other groups (p<0.001). There were significant differences in IOP readings between Group A and other groups at the last follow-up (p<0.05). The concentration of Group A maintained stable for over 2 weeks, drops from (10.56 +/ 0.05) ng/ml at day 3 to (7.74 +/-0.05) ng/ml at day 14. The number of corneal endothelial cells of Group A was not statistically significant between pre and post-operation. Histologic examination demonstrated that eyes treated with Sirolimus, especially the Sirolimus sustained delivery film, showed an obvious reduction in subconjunctival fibroblast scar tissue formation compared with no drug treatment groups, and had minimal evidence of inflammatory cell infiltration and new collagen deposition in the subconjunctiva. Immunohistochemistry assay showed that PCNA-expression was lower in the Group A (16.25+/-3.24%) compared to other groups (p<0.01). TUNEL assay showed a significant increase in the number of apoptotic fibroblasts around the surgical area in Group A and Group C (9.75+/ 1.71% and 8.50+/-1.92%) compared to the Group B and D (p<0.01). CONCLUSIONS: Sirolimus drug sustained delivery film can inhibit inflammatory cell activity, impede fibroblast proliferation activity, and induce fibroblast apoptosis in the filtration surgery sites in rabbit. The results indicate a safe and effective treatment strategy in anti-scaring treatment in glaucoma surgery. PMID- 21976961 TI - Cellular pharmacokinetic and pharmacodynamic analyses of ethacrynic acid: Implications in topical drug delivery in the eye. AB - PURPOSE: Ethacrynic acid (ECA) is a potential trabecular meshwork (TM) drug that has shown promising results in preclinical studies for treatment of primary open angle glaucoma. However, topical application of ECA is currently limited by adverse effects in corneal tissues. To this end, we developed a new theoretical model to evaluate time-dependent toxicity induced by ECA in corneal epithelial cells. METHODS: The model consisted of a cellular pharmacokinetic (PK) module to determine intracellular concentration of ECA, and a pharmacodynamic (PD) module to determine the cytotoxicity of ECA. It was assumed that ECA-induced cytotoxicity depended on drug exposure time and peak concentration of bound ECA in cells. In addition to the model development, we experimentally determined the intracellular concentration of ECA as a function of drug dose and treatment time. RESULTS: The intracellular concentration increased linearly (i.e., no saturation) with increasing the dose of ECA. It also increased initially with time and then reached a steady-state at ~40 min. The percent of cells survived after treatment decreased with increasing the dose of drug or the time of treatment. The experimental data were fit by the new PK and PD models to obtain values of model constants. One of the unique applications of these models was to predict cell survival relative to control when extracellular concentration of ECA varied with time. The prediction showed that the toxicity of ECA might be significantly overestimated by using the traditional LC(50) determined in vitro. CONCLUSIONS: The new PK and PD models developed in this study were capable to fit experimental data and predict time-dependent toxicity of ECA in corneal epithelial cells. The models may be useful for optimizing the dose and schedule in topical application of ECA for glaucoma treatment. PMID- 21976962 TI - Intraretinal calcium channels and retinal morbidity in experimental retinopathy of prematurity. AB - PURPOSE: To test the hypothesis that intraretinal calcium channels participate in retinal morbidity in a variable oxygen (VO) model of retinopathy of prematurity. METHODS: In control and VO Long Evans (LE) rats, either untreated or treated with voltage- or ligand-gated calcium channel antagonists, we measured retinal neovascular (NV) incidence and severity (adenosine diphosphatase staining), and retinal thickness and intraretinal ion channel activity (manganese-enhanced magnetic resonance imaging). Comparisons with the commonly studied Sprague Dawley rats were performed. Visual performance (optokinetic tracking) in untreated VO LE rats was also evaluated. RESULTS: In control LE rats, specific L-type voltage calcium channel antagonism, but not ligand-gated channel blockers, suppressed retinal manganese accumulation, while the inhibition of L-type channels normalized intraretinal uptake in VO LE rats. VO LE rats developed more severe NV than VO Sprague Dawley rats. Following VO, both strains demonstrated significant and similar degrees of retinal thinning and supernormal intraretinal manganese uptake. However, over time, intraretinal uptake remained elevated only in VO LE rats. Visual performance was subnormal in VO LE rats. L-type voltage-gated calcium channel antagonism reduced NV severity by 28% (p<0.05) in experimental LE rats compared to that in the control group. CONCLUSIONS: Abnormal intraretinal calcium channel activity is linked with retinal morbidity in experimental retinopathy of prematurity. PMID- 21976963 TI - VSX2 mutations in autosomal recessive microphthalmia. AB - PURPOSE: To further explore the spectrum of mutations in the Visual System Homeobox 2 (VSX2/CHX10) gene previously found to be associated with autosomal recessive microphthalmia. METHODS: We screened 95 probands with syndromic or isolated developmental ocular conditions (including 55 with anophthalmia/microphthalmia) for mutations in VSX2. RESULTS: Homozygous mutations in VSX2 were identified in two out of five consanguineous families with isolated microphthalmia. A novel missense mutation, c.668G>C (p.G223A), was identified in a large Pakistani family with multiple sibships affected with bilateral microphthalmia. This p.G223A mutation affects the conserved CVC motif that was shown to be important for DNA binding and repression activities of VSX2. The second mutation, c.249delG (p.Leu84SerfsX57), was identified in an Iranian family with microphthalmia; this mutation has been previously reported and is predicted to generate a severely truncated mutant protein completely lacking the VSX2 homeodomain, CVC domain and COOH-terminal regions. CONCLUSIONS: Mutations in VSX2 represent an important cause of autosomal recessive microphthalmia in consanguineous pedigrees. Identification of a second missense mutation in the CVC motif emphasizes the importance of this region for normal VSX2 function. PMID- 21976964 TI - Characterization of an effective CTL response against HIV and SIV infections. AB - A vaccine inducing protective immunity in mucosal tissues and secretions may stop or limit HIV infection. Although cytotoxic T lymphocytes (CTLs) are clearly associated with control of viral replication in HIV and simian immunodeficiency virus (SIV) infections, there are examples of uncontrolled viral replication in the face of strong CD8+ T-cell responses. The number of functions, breadth, avidity, and magnitude of CTL response are likely to be important factors in the effectiveness of anti-HIV T-cell response, but the location and persistence of effector CD8+ T cells are also critical factors. Although the only HIV vaccine clinical trial targeting cellular immunity to prevent HIV infection failed, vaccine strategies using persistent agents against pathogenic mucosal challenge in macaque models are showing unique success. Thus, the key to control the initial focus of viral replication at the portal of entry may rely on the continuous generation of effector CTL responses at mucosal level. PMID- 21976965 TI - Ketamine inhibits lung fluid clearance through reducing alveolar sodium transport. AB - Ketamine is a broadly used anaesthetic for analgosedation. Accumulating clinical evidence shows that ketamine causes pulmonary edema with unknown mechanisms. We measured the effects of ketamine on alveolar fluid clearance in human lung lobes ex vivo. Our results showed that intratracheal instillation of ketamine markedly decreased the reabsorption of 5% bovine serum albumin instillate. In the presence of amiloride (a specific ENaC blocker), fluid resolution was not further decreased, suggesting that ketamine could decrease amiloride-sensitive fraction of AFC associated with ENaC. Moreover, we measured the regulation of amiloride sensitive currents by ketamine in A549 cells using whole-cell patch clamp mode. Our results suggested that ketamine decreased amiloride-sensitive Na+ currents (ENaC activity) in a dose-dependent fashion. These data demonstrate that reduction in lung ENaC activity and lung fluid clearance following administration of ketamine may be the crucial step of the pathogenesis of resultant pulmonary edema. PMID- 21976966 TI - Higher molecular weight polyethylene glycol increases cell proliferation while improving barrier function in an in vitro colon cancer model. AB - Polyethylene glycol (PEG) has been previously shown to protect against enteric pathogens and prevent colon cancer invasion. To determine if PEG could indeed protect against previously observed pro-invasive effects of commensal E. coli and EPEC, Caco-2 cells grown in an in vitro model of colon cancer were infected with strains of human commensal E. coli or EPEC and treated with 10% PEG 3350, PEG 8000, and PEG 20,000, respectively. At 24 hours after infection, MMP-1 and MMP-13 activities, cell cluster thickness, depth of invasion, and proliferation were determined using standard molecular biology techniques and advanced imaging. We found that higher molecular weight PEG, especially PEG 8000 and 20,000, regardless of bacterial infection, increased proliferation and depth of invasion although a decrease in cellular density and MMP-1 activity was also noted. Maximum proliferation and depth of invasion of Caco-2 cells was observed in scaffolds treated with a combination of commensal E. coli strain, HS4 and PEG 8000. In conclusion, we found that PEG 8000 increased cell proliferation and led to the preservation of cell density in cells treated with commensal bacteria. This is important, because the preservation of a proliferative response in colon cancer results in a more chemo-responsive tumor. PMID- 21976967 TI - Novel stromal biomarkers in human breast cancer tissues provide evidence for the more malignant phenotype of estrogen receptor-negative tumors. AB - Research efforts were focused on genetic alterations in epithelial cancer cells. Epithelial-stromal interactions play a crucial role in cancer initiation, progression, invasion, angiogenesis, and metastasis; however, the active role of stroma in human breast tumorigenesis in relation to estrogen receptor (ER) status of epithelial cells has not been explored. Using proteomics and biochemical approaches, we identified two stromal proteins in ER-positive and ER-negative human breast cancer tissues that may affect malignant transformation in breast cancer. Two putative biomarkers, T-cell receptor alpha (TCR-alpha) and zinc finger and BRCA1-interacting protein with a KRAB domain (ZBRK1), were detected in leukocytes of ER-positive and endothelial cells of ER-negative tissues, respectively. Our data suggest an immunosuppressive role of leukocytes in invasive breast tumors, propose a multifunctional nature of ZBRK1 in estrogen receptor regulation and angiogenesis, and demonstrate the aggressiveness of ER negative human breast carcinomas. This research project may identify new stromal drug targets for the treatment of breast cancer patients. PMID- 21976968 TI - Simple and specific dual-wavelength excitable dye staining for glycoprotein detection in polyacrylamide gels and its application in glycoproteomics. AB - In this study, a commercially available fluorescent dye, Lissamine rhodamine B sulfonyl hydrazine (LRSH), was designed to specifically stain the glycoproteins in polyacrylamide gels. Through the periodate/Schiff base mechanism, the fluorescent dye readily attaches to glycoproteins and the fluorescence can be simultaneously observed under either 305 nm or 532 nm excitation therefore, the dye-stained glycoproteins can be detected under a regular UV transilluminator or a more elegant laser-based gel scanner. The specificity and detection limit were examined using a standard protein mixture in polyacrylamide gels in this study. The application of this glycoprotein stain dye was further demonstrated using pregnancy urine samples. The fluorescent spots were further digested in gel and their identities confirmed through LC-MS/MS analysis and database searching. In addition, the N-glycosylation sites of LRSH-labeled uromodulin were readily mapped via in-gel PNGaseF deglycosylation and LC-MS/MS analysis, which indicated that this fluorescent dye labeling does not interfere with enzymatic deglycosylation. Hence, the application of this simple and specific dual wavelength excitable dye staining in current glycoproteome research is promising. PMID- 21976969 TI - Upregulated expression of cytotoxicity-related genes in IFN-gamma knockout mice with Schistosoma japonicum infection. AB - It is well accepted that IFN-gamma is important to the development of acquired resistance against murine schistosomiasis. However, the in vivo role of this immunoregulatory cytokine in helminth infection needs to be further investigated. In this study, parasite burden and host immune response were observed in IFN gamma knockout mice (IFNg KO) infected with Schistosoma japonicum for 6 weeks. The results suggested that deficiency in IFN-gamma led to decreased egg burden in mice, with low schistosome-specific IgG antibody response and enhanced activation of T cells during acute infection. Microarray and qRT-PCR data analyses showed significant upregulation of some cytotoxicity-related genes, including those from the granzyme family, tumor necrosis factor, Fas Ligand, and chemokines, in the spleen cells of IFNg KO mice. Furthermore, CD8+ cells instead of NK cells of IFNg KO mice exhibited increased transcription of cytotoxic genes compared with WT mice. Additionally, Schistosoma japonicum-specific egg antigen immunization also could activate CD8+ T cells to upregulate the expression of cytotoxic genes in IFNg KO mice. Our data suggest that IFN-gamma is not always a positive regulator of immune responses. In certain situations, the disruption of IFN-gamma signaling may up-regulate the cytotoxic T-cell-mediated immune responses to the parasite. PMID- 21976970 TI - Inequalities and duality in gene coexpression networks of HIV-1 infection revealed by the combination of the double-connectivity approach and the Gini's method. AB - The symbiosis (Sym) and pathogenesis (Pat) is a duality problem of microbial infection, including HIV/AIDS. Statistical analysis of inequalities and duality in gene coexpression networks (GCNs) of HIV-1 infection may gain novel insights into AIDS. In this study, we focused on analysis of GCNs of uninfected subjects and HIV-1-infected patients at three different stages of viral infection based on data deposited in the GEO database of NCBI. The inequalities and duality in these GCNs were analyzed by the combination of the double-connectivity (DC) approach and the Gini's method. DC analysis reveals that there are significant differences between positive and negative connectivity in HIV-1 stage-specific GCNs. The inequality measures of negative connectivity and edge weight are changed more significantly than those of positive connectivity and edge weight in GCNs from the HIV-1 uninfected to the AIDS stages. With the permutation test method, we identified a set of genes with significant changes in the inequality and duality measure of edge weight. Functional analysis shows that these genes are highly enriched for the immune system, which plays an essential role in the Sym-Pat duality (SPD) of microbial infections. Understanding of the SPD problems of HIV-1 infection may provide novel intervention strategies for AIDS. PMID- 21976971 TI - Effective colon cancer prophylaxis in mice using embryonic stem cells and carbon nanotubes. AB - INTRODUCTION: In recent years, a new concept of an anticancer vaccine has been proposed to prevent and control the proliferation and expansion of cancer cells by eliciting an immune boost in biological systems. The recent literature supports the role of embryonic stem cells (ESC) as cellular agents that stimulate the biological systems to destroy cancer cells. However, at present, a true anticancer vaccine remains elusive. There are several lines of evidence showing that carbon nanotubes may be used to initiate and maintain immune responses. OBJECTIVE: The authors proposed to test the therapeutic potential of multiwalled carbon nanotubes (MWCNTs) combined with ESC as agents to induce an immune boost and provide subsequent anticancer protection in mice. METHODS: C57 BL/6 mice were immunized with ESC and MWCNTs. RESULTS: The proposed vaccine led to significant antitumor responses and enhanced tumor rejection in mice with subcutaneous inoculation of MC38 colon malign cells compared with groups only administered ESC, only MWCNTs, and controls. CONCLUSION: The application and potential of ESC combined with MWCNTs as anticancer immunization agents may represent the beginning of a new chapter in the treatment of colon cancer. PMID- 21976972 TI - Doxorubicin-loaded PEG-PCL copolymer micelles enhance cytotoxicity and intracellular accumulation of doxorubicin in adriamycin-resistant tumor cells. AB - BACKGROUND: Multidrug resistance remains a major obstacle to successful cancer chemotherapy. Some chemical multidrug resistance inhibitors, such as ciclosporin and verapamil, have been reported to reverse resistance in tumor cells. However, the accompanying side effects have limited their clinical application. In this study, we have developed a novel drug delivery system, ie, a polyethyleneglycol polycaprolactone (PEG-PCL) copolymer micelle encapsulating doxorubicin, in order to circumvent drug resistance in adriamycin-resistant K562 tumor cells. METHODS: Doxorubicin-loaded diblock copolymer PEG-PCL micelles were developed, and the physicochemical properties of these micelles, and accumulation and cytotoxicity of doxorubicin in adriamycin-resistant K562 tumor cells were studied. RESULTS: Doxorubicin-loaded micelles were prepared using a solvent evaporation method with a diameter of 36 nm and a zeta potential of +13.8 mV. The entrapment efficiency of doxorubicin was 48.6% +/- 2.3%. The micelles showed sustained release, increased uptake, and cellular cytotoxicity, as well as decreased efflux of doxorubicin in adriamycin-resistant K562 tumor cells. CONCLUSION: This study suggests that PEG-PCL micelles have the potential to reverse multidrug resistance in tumor cells. PMID- 21976973 TI - Thiolated chitosan nanoparticles as a delivery system for antisense therapy: evaluation against EGFR in T47D breast cancer cells. AB - Thiolated chitosan has high transfection and mucoadhesive properties. We investigated the potential of two recently synthesized polymers: NAC-C (N-acetyl cysteine-chitosan) and NAP-C (N-acetyl penicillamine-chitosan) in anticancer drug delivery targeting epidermal growth factor receptor (EGFR). Doxorubicin (DOX) and antisense oligonucleotide (ASOND)-loaded polymer nanoparticles were prepared in water by a gelation process. Particle characterization, drug loading, and drug release were evaluated. To verify drug delivery efficiency in vitro experiments on a breast cancer cell line (T47D) were performed. EGFR gene and protein expression was analyzed by real time quantitative polymerase chain reaction and Western blotting, respectively. A loading percentage of 63% +/- 5% for ASOND and 70% +/- 5% for DOX was achieved. Drug release data after 15 hours showed that ASOND and DOX were completely released from chitosan-based particles while a lower and more sustained release of only 22% +/- 8% was measured for thiolated particles. In a cytosol simulated release medium/reducing environment, such as found intracellularly, polymer-based nanoparticles dissociated, liberating approximately 50% of both active substances within 7 hours. ASOND-loaded polymer nanoparticles had higher stability and high mucoadhesive properties. The ASOND loaded thiolated particles significantly suppressed EGFR gene expression in T47D cells compared with ASOND-loaded chitosan particles and downregulated EGFR protein expression in cells. This study could facilitate future investigations into the functionality of NAP-C and NAC-C polymers as an efficient ASOND delivery system in vitro and in vivo. PMID- 21976974 TI - Targeted delivery of doxorubicin-utilizing chitosan nanoparticles surface functionalized with anti-Her2 trastuzumab. AB - BACKGROUND: Targeting drugs to their sites of action to overcome the systemic side effects associated with most antineoplastic agents is still a major challenge in pharmaceutical research. In this study, the monoclonal antibody, trastuzumab, was used as a targeting agent in nanoparticles carrying the antitumor drug, doxorubicin, specifically to its site of action. METHODS: Chitosan-doxorubicin conjugation was carried out using succinic anhydride as a crosslinker. Trastuzumab was conjugated to self-assembled chitosan-doxorubin conjugate (CS-DOX) nanoparticles (particle size, 200 nm) via thiolation of lysine residues and subsequent linking of the resulted thiols to chitosan. Conjugation was confirmed by gel permeation chromatography, differential scanning calorimetry, Fourier transform infrared spectroscopy, and (1)H nuclear magnetic resonance spectroscopy studies. Dynamic light scattering, transmission electron microscopy, and zeta potential determination were used to characterize the nanoparticles. RESULTS: CS-DOX conjugated nanoparticles had a spherical shape and smooth surface with a narrow size distribution and core-shell structure. Increasing the ratio of doxorubicin to chitosan in the conjugation reaction gave rise to a higher doxorubicin content but lower conjugation efficiency. Trastuzumab-decorated nanoparticles (CS-DOX-mAb) contained 47 MUg/mg doxorubicin and 33.5 MUg/mg trastuzumab. Binding of trastuzumab to the nanoparticles was further probed thermodynamically by isothermal titration calorimetry. Fluorescence microscopy demonstrated enhanced and selective uptake of CS-DOX-mAb by Her2+ cancer cells compared with nontargeted CS-DOX nanoparticles and free drug. CONCLUSION: Antibody-conjugated nanoparticles were shown to discriminate between Her2+ and Her2- cells, and thus have the potential to be used in active targeted drug delivery, with reduction of drug side effects in Her2+ breast and ovarian cancers. PMID- 21976975 TI - Anti-DR5 monoclonal antibody-mediated DTIC-loaded nanoparticles combining chemotherapy and immunotherapy for malignant melanoma: target formulation development and in vitro anticancer activity. AB - BACKGROUND: The increased incidence of malignant melanoma in recent decades, along with its high mortality rate and pronounced resistance to therapy pose an enormous challenge. Novel therapeutic strategies, such as immunotherapy and targeted therapy, are urgently needed for melanoma. In this study, a new active targeting drug delivery system was constructed to combine chemotherapy and active specific immunotherapy. METHODS: The chemotherapeutic drug, dacarbazine (DTIC), that induces apoptosis through the intrinsic pathway which typically responds to severe DNA damage, was used as a model drug to prepare DTIC-loaded polylactic acid (PLA) nanoparticles (DTIC-NPs), which were covalently conjugated to a highly specific targeting functional TRAIL-receptor 2 (DR5) monoclonal antibody (mAb) that can contribute directly to cancer cell apoptosis or growth inhibition through the extrinsic pathway. RESULTS: Our in vitro experiments demonstrated that DTIC-PLA-DR5 mAb nanoparticles (DTIC-NPs-DR5 mAb) are an active targeting drug delivery system which can specifically target DR5-overexpressing malignant melanoma cells and become efficiently internalized. Most strikingly, compared with conventional DTIC-NPs, DTIC-NPs-DR5 mAb showed significantly enhanced cytotoxicity and increased cell apoptosis in DR5-positive malignant melanoma cells. CONCLUSION: The DTIC-NPs-DR5 mAb described in this paper might be a potential formulation for targeting chemotherapy and immunotherapy to DR5 overexpressing metastatic melanoma. PMID- 21976976 TI - Nanotherapeutics in angiogenesis: synthesis and in vivo assessment of drug efficacy and biocompatibility in zebrafish embryos. AB - BACKGROUND: Carbon nanotubes have shown broad potential in biomedical applications, given their unique mechanical, optical, and chemical properties. In this pilot study, carbon nanotubes have been explored as multimodal drug delivery vectors that facilitate antiangiogenic therapy in zebrafish embryos. METHODS: Three different agents, ie, an antiangiogenic binding site (cyclic arginine glycin-easpartic acid), an antiangiogenic drug (thalidomide), and a tracking dye (rhodamine), were conjugated onto single-walled carbon nanotubes (SWCNT). The biodistribution, efficacy, and biocompatibility of these triple functionalized SWCNT were tested in mammalian cells and validated in transparent zebrafish embryos. RESULTS: Accumulation of SWCNT-associated nanoconjugates in blastoderm cells facilitated drug delivery applications. Mammalian cell xenograft assays demonstrated that these antiangiogenic SWCNT nanoconjugates specifically inhibited ectopic angiogenesis in the engrafted zebrafish embryos. CONCLUSION: This study highlights the potential of using SWCNT for generating efficient nanotherapeutics. PMID- 21976977 TI - Investigation of folate-conjugated fluorescent silica nanoparticles for targeting delivery to folate receptor-positive tumors and their internalization mechanism. AB - Multifunctionalized nanoparticles (NPs) are emerging as ideal tools for gene/drug delivery, bioimaging, labeling, or intracellular tracking in biomedical applications, and have attracted considerable attention owing to their unique advantages. In this study, fluorescent silica NPs were synthesized by a modified Stober method using conjugates of 3-mercaptopropyltrimethoxysilane (MPS) and maleimide-fluorescein isothiocyanate (maleimide-FITC). Mean diameters of the NPs were controlled between 212-2111 nm by regulating MPS concentration in the reaction mixture. Maleimide-FITC molecules were doped into NPs or conjugated to the surface of NPs through the chemical reaction of maleimide and thiol groups. The data showed that the former NPs are better than the latter by comparing their fluorescence intensity. Furthermore, folate molecules were linked to the FITC doped silica NPs by using polyethylene glycol (PEG) (NH2-PEG-maleimide) as a spacer, thus forming folate receptor targeting fluorescent NPs, referred to as NPs(FITC)-PEG-Folate. The quantitative analysis of cellular internalization into different cancer cells showed that the delivery efficiency of KB cells (folate receptor-positive cells) is more than six-fold higher than that of A549 cells (folate receptor-negative cells). The delivery efficiency of KB cells decreased significantly after free folate addition to the cell culture medium because the folate receptors were occupied by the free folate. The NPs endocytosis mechanism was also investigated. It was shown that clathrin, an inhibitor of cell phagocytosis, markedly decreased the NPs uptake into KB cells, suggesting that it plays an important role in NPs cellular internalization. These results demonstrated that the novel particles of NPs(FITC)-PEG-Folate are promising for fluorescent imaging or targeting delivery to folate receptor-positive tumors. PMID- 21976978 TI - SERS-based nanobiosensing for ultrasensitive detection of the p53 tumor suppressor. AB - BACKGROUND: One of the main challenges in biomedicine is improvement of detection sensitivity to achieve tumor marker recognition at a very low concentration when the disease is not significantly advanced. A pivotal role in cancer defense is played by the p53 tumor suppressor, therefore its detection with high sensitivity may contribute considerably to early diagnosis of cancer. In this work, we present a new analytical method based on surface-enhanced Raman spectroscopy which could significantly increase the sensitivity of traditional bioaffinity techniques. p53 molecules were anchored to gold nanoparticles by means of the bifunctional linker 4-aminothiophenol (4-ATP). The characteristic vibrational bands of the p53-4-ATP nanoparticle system were then used to identify the p53 molecules when they were captured by a recognition substrate comprising a monolayer of azurin in molecules possessing significant affinity for this tumor suppressor. The Raman signal enhancement achieved by 4-ATP-mediated crosslinking of p53 to 50 nm gold nanoparticles enabled detect of this protein at a concentration down to 5 * 10-13 M. PMID- 21976979 TI - Adhesion of bio-functionalized ultrasound microbubbles to endothelial cells by targeting to vascular cell adhesion molecule-1 under shear flow. AB - The expression of certain endothelial cell adhesion molecules is increased during endothelial dysfunction or inflammatory activation. This has led to the concept of using microbubbles for targeted molecular imaging or drug delivery. In this approach, microbubbles with a specific ligand to receptors expressed at the site of specific diseases are constructed. The present study aimed to engineer a novel type of bio-functionalized microbubbles (vascular cell adhesion molecule 1 [VCAM 1]-targeted microbubbles), and determine whether VCAM-1-targeted microbubbles exhibit specific adhesion to lipopolysaccharide (LPS)-activated endothelial cells. Our data showed that VCAM-1 expression was significantly upregulated in both LPS-activated endothelial cells in vitro and endothelium in a rat atherosclerosis model in vivo. Targeted microbubbles were designed by conjugating anti-VCAM-1 monoclonal antibodies to the shell of microbubbles using biotin avidin bridging chemistry methods. Microbubble adhesion to endothelial cells was assessed in a flow chamber at two shear stress conditions (6.3 and 10.4 dynes/cm2). Our data showed that microbubble adhesion depends on both the surface anti-VCAM-1 antibody densities and the exposed shear stresses. Adhesion of VCAM-1 targeted microbubbles onto LPS-activated endothelial cells increased with the surface antibody densities, and decreased with the exposed shear stresses. These findings showed that the specific ligand-carrying microbubbles have considerable potential in targeted ultrasound molecular imaging or ultrasound-assisted drug/gene delivery applications. PMID- 21976980 TI - Effects of a novel pH-sensitive liposome with cleavable esterase-catalyzed and pH responsive double smart mPEG lipid derivative on ABC phenomenon. AB - BACKGROUND: The ABC phenomenon is described as a syndrome of accelerated clearance of polyethylene glycol (PEG)-modified liposomes from the bloodstream when repeatedly injected, with their increased accumulation in the liver and spleen. METHODS: To clarify this immune response phenomenon, we evaluated a novel modified pH-sensitive liposome with a cleavable double smart PEG-lipid derivative (mPEG-Hz-CHEMS). RESULTS: The ABC phenomenon in mice was brought about by repeated injection of conventional PEG-PE liposomes and was accompanied by a greatly increased uptake in the liver. However, a slight ABC phenomenon was brought about by repeated injection of mPEG-CHEMS liposomes and was accompanied by only a slightly increased uptake in the liver, and repeated injection of mPEG Hz-CHEMS liposomes did not induce the ABC phenomenon and there was no increase in liver accumulation. This finding indicates that the cleavable mPEG-Hz-CHEMS derivative could lessen or eliminate the ABC phenomenon induced by repeated injection of PEGylated liposomes. CONCLUSION: This research has shed some light on a solution to the ABC phenomenon using a cleavable PEG-Hz-CHEMS derivative encapsulated in nanoparticles. PMID- 21976981 TI - Solvent effects on structural and thermochemical properties of p53 tumor suppressor gene: a molecular modeling approach in drug design. AB - The p53 tumor-suppressor protein is a cellular phosphoprotein and a negative regulator of cell growth. Most p53 mutations occur in exons 5-8 within the DNA binding domain. Therefore, p53 can potentially be targeted with novel drugs designed to bind to a mutation and restore its stability or wild-type conformation. For the current study, Hartree-Fock calculations were used to investigate the solvent-induced effects of five different solvent media (acetone, ethanol, methanol, dimethyl sulfoxide, and water) on the thermochemical parameters and relative energies, and on the multinuclear nuclear magnetic resonance shielding tensors of oxygen, nitrogen, and phosphorus nuclei, of GAT. To understand how the solvent affects the mutation region (the "hot spot") of p53, the relative energies of GAT in selected solvent media were determined. Some biological evidence suggested the structural stabilities of hot spots of GAT have the optimum temperature and solvent type for mutation. All the authors' findings are in accordance with common biological phenomena. Another important objective of this study was to compare the hydration Gibbs free energies of CUA and GAT in water using two different approaches where the solvent was treated as a continuum of the constant at different levels of Hartree-Fock theory. The Gibbs hydration energy values obtained in water with the polarized continuum model directly applied on the isolated CUA and GAT sequences were compared with those determined from the hydrated models with four, six, and eight water molecule clusters around the hot spots uracil and adenine. The clustered structures of water molecules around the hot spots of GAT (in DNA level) and CUA (in transcriptional level) were found to be energetically favored. The results of this study provide a reliable insight into the nature of mutation processes, which is of utmost importance for the study of biochemical structures, and provide a basis for drug design. PMID- 21976982 TI - Size-dependent in vivo toxicity of PEG-coated gold nanoparticles. AB - BACKGROUND: Gold nanoparticle toxicity research is currently leading towards the in vivo experiment. Most toxicology data show that the surface chemistry and physical dimensions of gold nanoparticles play an important role in toxicity. Here, we present the in vivo toxicity of 5, 10, 30, and 60 nm PEG-coated gold nanoparticles in mice. METHODS: Animal survival, weight, hematology, morphology, organ index, and biochemistry were characterized at a concentration of 4000 MUg/kg over 28 days. RESULTS: The PEG-coated gold particles did not cause an obvious decrease in body weight or appreciable toxicity even after their breakdown in vivo. Biodistribution results show that 5 nm and 10 nm particles accumulated in the liver and that 30 nm particles accumulated in the spleen, while the 60 nm particles did not accumulate to an appreciable extent in either organ. Transmission electron microscopic observations showed that the 5, 10, 30, and 60 nm particles located in the blood and bone marrow cells, and that the 5 and 60 nm particles aggregated preferentially in the blood cells. The increase in spleen index and thymus index shows that the immune system can be affected by these small nanoparticles. The 10 nm gold particles induced an increase in white blood cells, while the 5 nm and 30 nm particles induced a decrease in white blood cells and red blood cells. The biochemistry results show that the 10 nm and 60 nm PEG-coated gold nanoparticles caused a significant increase in alanine transaminase and aspartate transaminase levels, indicating slight damage to the liver. CONCLUSION: The toxicity of PEG-coated gold particles is complex, and it cannot be concluded that the smaller particles have greater toxicity. The toxicity of the 10 nm and 60 nm particles was obviously higher than that of the 5 nm and 30 nm particles. The metabolism of these particles and protection of the liver will be more important issues for medical applications of gold-based nanomaterials in future. PMID- 21976984 TI - Pattern of deaths in females in a tertiary health center, south-west Nigeria. AB - PURPOSE: The aim of this study was to review autopsies to determine the pattern of deaths in females at Wesley Guild Hospital, Ilesa, Nigeria. METHODS: A 9-year retrospective study was done of all autopsies done on females in the Department of Morbid Anatomy and Forensic Medicine, Obafemi Awolowo University Teaching Hospitals Complex, Wesley Guild Hospital, Ilesa, Nigeria, from January 2002 to December 2010. Records of all autopsies done on females during the period were reviewed. RESULTS: During the study period 215 cases of female death were autopsied. The age range was 0-75 years (mean = 32.9). Deaths due to trauma were most common (57.2%), followed by obstetric deaths (15.8%). Deaths due to infections and cardiovascular diseases accounted for 13% and 5.6%, respectively. Injuries sustained from automobile accidents were responsible for 88.6% of all trauma deaths. Gunshot injuries accounted was 4.9% of these trauma deaths. The causes of death from automobile accidents included multiple injuries (49.5%), head injury (38.5%), and hypovolemia (8.3%). Obstetric deaths were predominantly due to uterine sepsis (51.5%) and hemorrhagic shock (39.4%). About 39% of deaths from infection were due to septicemia. Acute bacterial meningitis, acute lobar pneumonia, and malaria caused 23.1%, 15.4%, and 7.7% of deaths from infections, respectively. Four cases of sudden unnatural deaths (other than trauma) were recorded. CONCLUSION: Trauma was the most common cause of death in women autopsied in our hospital, and automobile injuries were the most common causes of these trauma deaths. Obstetric deaths ranked second. Sepsis and hemorrhage were the most common causes of these obstetric deaths. Deaths from eclampsia were low. Requests for autopsies on women who died from cancer were few. There is a need for clinicians to ascertain the actual cause of death in women who die from cancer. PMID- 21976983 TI - Antibacterial treatment of bacterial vaginosis: current and emerging therapies. AB - Bacterial vaginosis is a common cause of malodorous vaginal discharge. It is also associated with sexually transmitted infections and adverse pregnancy outcomes. The magnitude of the gynecological and obstetrical consequences has stimulated therapeutic research and led to the testing of several therapies. The objective of this work is to present the currently available therapeutic strategies for the treatment of bacterial vaginosis and associated recommendations, and discuss the emerging therapies. PMID- 21976985 TI - Knowledge of and attitude toward human papillomavirus infection and vaccines among female nurses at a tertiary hospital in Nigeria. AB - BACKGROUND: Persistent infection with high-risk types of human papillomavirus (HPV) is a prerequisite for the development of cervical cancer. Highly immunogenic HPV vaccines have been developed and licensed for the primary prevention of cervical cancer in some developed and developing countries. This calls for assessment of the knowledge of the HPV infection and the acceptability of the HPV vaccines among health care providers. OBJECTIVE: The aim of this study was to assess awareness and knowledge of HPV infection and vaccines and to assess attitude toward these vaccines among female nurses at Lagos University Teaching Hospital, Lagos, Nigeria. STUDY DESIGN: The study was a cross-sectional, descriptive study using a pretested, structured, anonymous, self-administered, 19 item questionnaire. RESULTS: A total of 178 female nurses were interviewed during a 4-week period. The mean age of respondents was 37.1 +/- 3.1 years. Almost all (99.4%) of the respondents had heard of cervical cancer, while about 85% of them had heard of HPV infection. Only a quarter (25.3%) of respondents had heard of the HPV vaccines, and of those only 26.7% knew the vaccines were for the prevention of cervical cancer. Most (70.2%) of the nurses expressed a desire to be vaccinated and 120 (67.4%) supported the vaccination of preadolescent girls. Those who expressed a willingness to be vaccinated were more likely to recommend HPV vaccination for preadolescent girls. CONCLUSION: Overall, there was a poor knowledge of the HPV vaccines among female nurses at Lagos University Teaching Hospital. Despite this poor knowledge, most of the nurses expressed a strong desire to be vaccinated and their intention to recommend it for preadolescent girls. The main reason given overall for not recommending the vaccines was lack of information. There is an urgent need to bridge this information gap. PMID- 21976986 TI - Taxonomic review of the postica-group of Fannia Robineau-Desvoidy (Diptera, Fanniidae) from China, with the description of one new species. AB - The Chinese fauna of the Fannia postica-group Chillcott (1961) is reviewed, the diagnostic features of this group are redefined, one new species, Fannia nudifemoratasp. n., is described, and a key to the males of nine known species is given. One new junior synonym, Fannia tigripeda Xue, Wang&Li, syn. n. for Fannia stigi Rognes is established. To facilitate comparisons of the species, Fannia aethiops Malloch, Fannia ardua Nishida, Fannia discoculea Xue, Fannia ringdahlana Collin, Fannia postica (Stein), Fannia spathiophora Malloch, and Fannia stigi Rognes are redescribed and illustrated. The geographic distribution of the known Chinese species is updated. PMID- 21976987 TI - A new species of Megalommum Szepligeti (Hymenoptera, Braconidae, Braconinae); a parasitoid of the pistachio longhorn beetle (Calchaenesthes pistacivora Holzschuh; Coleoptera, Cerambycidae) in Iran. AB - A new species of the genus Megalommum Szepligeti (Hymenoptera: Braconidae: Braconinae), reared from the pistachio longhorn beetle (Calchaenesthes pistacivora Holzschuh; Coleoptera: Cerambycidae), is described and illustrated. The genera Curreia Ashmead, 1900 and Endovipio Turner, 1922 are new synonyms of Megalommum Szepligeti, 1900. Notes on the biology of Megalommum pistacivoraesp. n. and a key to the West Palaearctic and Oriental species are added. The following new combinations are given: Megalommum xanthoceps (Fahringer, 1928), comb. n.,Megalommum jacobsoni (Tobias, 1968), comb. n.,Megalommum ayyari (Watanabe, 1950), comb. n.,Megalommum philippinense (Baker, 1917), comb. n.,Megalommum dodecanesi(Ferriere, 1922), comb. n.,Megalommum ceresense (Turner, 1922), comb. n., Megalommum inareatum (Granger, 1949), comb. n.,Megalommum antefurcale (Szepligeti, 1915) comb. n. and Megalommum tibiale (Ashmead, 1906), comb. n. PMID- 21976988 TI - Taxonomy of the genus Metolinus Cameron (Coleoptera, Staphylinidae, Staphylininae, Xantholinini) from China with description of three new species. AB - This paper studies the taxonomy of the genus Metolinus Cameron, 1920 (Coleoptera: Staphylinidae, Staphylininae, Xantholinini) from China and describes three new species: Metolinus xizangensissp. n. from Xizang (Tibet), Metolinus emarginatussp. n. fromSichuan, and Metolinus binariussp. n. from Yunnan. The Chinese fauna of the genus is thus increased to 8 species in total. A key to eight Chinese species is provided. Female genital segments and other important morphological characters are illustrated in line drawings for the new species as well as Metolinus shanicus Bordoni, 2002 and Metolinus gardneri (Cameron, 1945). The text also provides color plates with habitus photographs and a map to show the species' geographical distribution pattern. The type specimens of the new species are deposited in Institute of Zoology, the Chinese Academy of Sciences (IZ-CAS). PMID- 21976989 TI - Notes on the genus Harmonicon F.O.P.-Cambridge, 1896 (Araneae, Dipluridae) with description of a new species from French Guyana. AB - Information on the genus Harmonicon F.O.P.-Cambridge, 1896, a key to the species and a new diagnosis differing from the one in Marechal and Marty (1998) are provided. A new species is described: Harmonicon oiapoqueae differing from other species of the genus by the morphology of the posterior sternal sigilla, the more recurved, inverted U-shaped fovea, the amount and arrangement of maxillary cuspules, a single row of teeth on the claws of the palpal tarsus, longer and more slender legs III and IV in females, longer embolus, thinner bulb, and longer, more slender legs in males. The status of the putative junior synonyms of Harmonicon, Pseudohermachura Mello-Leitao, 1927 and Prosharmonicon Mello-Leitao, as well as the two species formerly assigned to Harmonicon, Harmonicon nigridorsi Mello-Leitao, 1924 and Harmonicon riveti Simon, 1903, is discussed. PMID- 21976990 TI - Review of the genus Plistobunus Pocock, 1903, with description of a new species from Hainan Island, China (Opiliones, Laniatores, Epedanidae). AB - The genus Plistobunus Pocock, 1903 and its type species Plistobunus rapax Pocock, 1903 are redescribed based on the type material deposited in the British Museum of Natural History (BMNH), London. In addition, a new Plistobunus species from Hainan Island is described and illustrated of Plistobunus columnariussp. n. The new species is diagnosed by having a row of 12 setiferous tubercles on anterior margin of carapace, and the femur of pedipalpus ventrally with 13 setiferous tubercles in male. PMID- 21976991 TI - Chemosymbiotic bivalves from the mud volcanoes of the Gulf of Cadiz, NE Atlantic, with descriptions of new species of Solemyidae, Lucinidae and Vesicomyidae. AB - The chemosymbiotic bivalves collected from the mud volcanoes of the Gulf of Cadiz are reviewed. Of the thirteen species closely associated with chemosynthetic settings two Solemyidae, Solemya (Petrasma) elarraichensissp. n. and Acharax gadiraesp. n., one Lucinidae, Lucinoma asapheussp. n., and one Vesicomyidae, Isorropodon megadesmussp. n. are described and compared to close relatives of their respective families. The biodiversity and distribution of the chemosymbiotic bivalves in the Gulf of Cadiz are discussed and compared to the available information from other cold seeps in the Eastern Atlantic and Mediterranean. Although there is considerable similarity at the genus level between seep/mud volcano fields in the Eastern Atlantic and Mediterranean, there is little overlap at the species level. This indicates a high degree of endemism within chemosymbiotic bivalve assemblages. PMID- 21976992 TI - The dazed and confused identity of Agassiz's land tortoise, Gopherus agassizii (Testudines, Testudinidae) with the description of a new species, and its consequences for conservation. AB - We investigate a cornucopia of problems associated with the identity of the desert tortoise, Gopherus agassizii (Cooper). The date of publication is found to be 1861, rather than 1863. Only one of the three original cotypes exists, and it is designated as the lectotype of the species. Another cotype is found to have been destroyed in the 1906 San Francisco earthquake and subsequent fire. The third is lost. The lectotype is genetically confirmed to be from California, and not Arizona, USA as sometimes reported. Maternally, the holotype of Gopherus lepidocephalus (Ottley & Velazques Solis. 1989) from the Cape Region of Baja California Sur, Mexico is also from the Mojavian population of the desert tortoise, and not from Tiburon Island, Sonora, Mexico as previously proposed. A suite of characters serve to diagnose tortoises west and north of the Colorado River, the Mojavian population, from those east and south of the river in Arizona, USA, and Sonora and Sinaloa, Mexico, the Sonoran population. Species recognition is warranted and because Gopherus lepidocephalus is from the Mojavian population, no names are available for the Sonoran species. Thus, a new species, Gopherus morafkaisp. n., is named and this action reduces the distribution of Gopherus agassizii to only 30% of its former range. This reduction has important implications for the conservation and protection of Gopherus agassizii, which may deserve a higher level of protection. PMID- 21976993 TI - Two new cave rnicolous genera of Julidae (Diplopoda, Julida), with notes on the tribe Brachyiulini and on julid subanal hooks and anchors. AB - Two remarkable genera and species of the millipede family Julidae, Titanophyllum spiliarumgen. n., sp. n. and Mammamia profugagen. n. sp., n., are described from caves in Greece and Italy, respectively. The presence of a flagellum and the absence of a 'pro-mesomerital forceps' on the gonopods place them in the tribe Brachyiulini Verhoeff, 1909, an unnatural grouping based on plesiomorphic characters. Both are outstanding in being the only hitherto known blind julidans having such gonopodal features. A dichotomous key to the nine valid brachyiulinine genera based on peripheral and gonopodal characters is presented. Moreover, notes on subanal hooks and anchors in Julida are provided with hypotheses on their possible function. PMID- 21976994 TI - Baeopterogyna mihalyii Matile (Diptera, Mycetophilidae): association of sexes using morphological and molecular approaches with the first description of females. AB - Both males and females of Baeopterogyna mihalyiiMatile, 1975 are recorded from northern Greece. Females are described for the first time providing photographs of the general facies and terminalia. In contrast to the single congener with stenopterous females - Baeopterogyna nudipes Vockeroth, 1972 - Baeopterogyna mihalyii is shown to have normally developed wings in both sexes. Association of sexes is based on both morphological characters and sequence data from cytochrome oxidase subunit one (COI). DNA sequences are used for the first time for the association of sexes in Mycetophilidae. PMID- 21976995 TI - New species of the genus Cyamops Melander from New Zealand (Diptera, Periscelididae, Stenomicrinae). AB - Two new species of the genus Cyamops (Diptera: Periscelididae), the first from New Zealand, are described. The two newly described species are: Cyamops alessandrae and Cyamops crosbyi. A key to the genera of the subfamily Stenomicrinae and to the species of Cyamops from the Australasian/Oceanian Region and detailed illustrations of structures of the male terminalia are provided. PMID- 21976996 TI - Revision of the Neotropical caddisfly genus Itauara Muller, 1888 (Trichoptera, Glossosomatidae). AB - Systematics of the genus Itauara Muller, 1888 are reviewed. A generic diagnosis, illustrations, and descriptions are provided for males. The genus can be identified by several features of the male genitalia including an extremely reduced phallobase and a phallic apparatus that consists of a sclerotized dorsal sheath covering a very membranous ventral portion. A total 18 species are described as new: Itauara alexanderisp. n.(Brazil), Itaura bidentatasp. n. (Guyana), Itaura blahnikisp. n. (Brazil) Itaura charlottasp. n. (Brazil), Itaura emiliasp. n. (Brazil), Itaura flintisp. n. (Brazil), Itaura guyanensissp. n. (Guyana), Itaura jamesiisp. n. (Brazil), Itaura juliasp. n. (Brazil), Itaura lucindasp. n. (Brazil), Itaura ovissp. n. (Guyana, Venezuela), Itaura peruensissp. n. (Peru), Itaura rodmanisp. n. (Brazil), Itaura simplexsp. n. (Brazil), Itaura spiralissp. n. (Guyana), Itaura stellasp. n. (Brazil), Itaura tuscisp. n. (Brazil), and Itaura unidentatasp. n. (Guyana). These additions bring the total fauna of Itauara to 22 species. PMID- 21976997 TI - Description of two new species of Rissoella Gray, 1847 (Mollusca, Gastropoda, Heterobranchia) from Venezuela, with a key to the Caribbean species known for the genus. AB - Two new species of the genus Rissoella Gray, 1847 are described from Venezuela, one from the National Park Morrocoy, Rissoella morrocoyensissp. n. and the other from the Wildlife Refuge Isla de Aves, Rissoella venezolanicolasp. n.Rissoella morrocoyensissp. n. has a deep umbilicus (partly closed), preumbilical cord, black head, hypobranchial gland marked by a pale yellow boomerang-shaped ribbon and it lives on the leaves of the seagrass Thalassia testudinum Banks & Konig, 1805. Rissoella venezolanicolasp. n. has an angled preumbilical cord which extends to the columella delimiting a trapezoid, a hypobranchial gland marked by a yellow quaver-shaped ribbon and protoconch with fuchsia highlights. It lives on the brown alga Dictyota spp. The records of Rissoella in the Caribbean are revised and illustrations, a comparative table and a key to the Caribbean species known for the genus are provided. PMID- 21976998 TI - Notes on Pauropoda (Myriapoda) from USA, with descriptions of two new species. AB - Two new species of Pauropoda are described from USA, Kionopauropus alyeskaensissp. n. (Pauropodidae), and Eurypauropus arcuatussp. n. (Eurypauropodidae). The genus Kionopauropus is reported from the Western Hemisphere for the first time. PMID- 21977000 TI - Two new species of the genus Leenurina Najt & Weiner, 1992 (Collembola, Neanuridae, Caputanurininae) from Primorskij Kraj (Russia). AB - Leenurina khualazasp. n. and Leenurina pomorskiisp. n., two new species from East Russia (Primorskij Kraj) are described. They are closely related to Leenurina jasii Najt & Weiner, 1992 from North Korea, from which they differ mainly in the number of tibiotarsal chaetae (19, 19, 18 in the new species versus 18, 18, 17 in Leenurina jasii), several chaetotaxic features and organization of dorsal granulation. The two new species may be separated by tertiary granulation (large areas fringed with large secondary granules in Leenurina pomorskii, small rounded or hexagonal areas with smaller secondary granules in Leenurina khualaza), coloration (light blue in Leenurina khualaza versus white in Leenurina pomorskii) and number of eyes (2+2 eyes in Leenurina khualaza versus 3+3 eyes in Leenurina pomorskii). An updated diagnosis of the genus Leenurina Najt & Weiner, 1992 and a key to species of Caputanurininae are given. PMID- 21976999 TI - A new species of Buthus Leach, 1815 from Cyprus (Scorpiones, Buthidae). AB - During the last decade, several contributions to the genus Buthus Leach, 1815 (family Buthidae) and especially to the 'Buthus occitanus' species complex were proposed. These contributions led to the definition of several species, previously considered only as subspecies or varieties, and also to the description of new species. In the present study, the questionable presence of the genus Buthus in the Cyprus is rediscussed and a new species Buthus kuntisp. n. is described. PMID- 21977001 TI - On Hypolycaena from Maluku, Indonesia, including the first description of male Hypolycaena asahi (Lepidoptera, Lycaenidae). AB - The taxonomy and distribution of the five species of Hypolycaena in Maluku are discussed and new locality records given. Corrections are made to the published taxonomy and distribution of Hypolycaena phorbas (Fabricius, 1793). This clarification enables a better understanding of the biogeography of the genus. Hypolycaena asahi Okubo, 2007, was originally described from a single female from Ambon and is here recorded from Seram. The male is described for the first time. PMID- 21977002 TI - The subfamily Cheloninae (Hymenoptera, Braconidae) from Egypt, with the description of two new species. AB - A key to the chelonine species (Braconidae) (both recorded and recently collected) from Egypt is given. It includes 16 species, of which five species are new to the Egyptian fauna and two (Phanerotoma (Phanerotoma) elbaiensissp. n. and Phanerotoma (Bracotritoma) pontisp. n.) are new for science. A faunistic list and the description for the two new species are added. PMID- 21977003 TI - Long-term study of cloud condensation nuclei (CCN) activation of the atmospheric aerosol in Vienna. AB - During a total of 11 months, cloud condensation nuclei (CCN at super-saturation S 0.5%) and condensation nuclei (CN) concentrations were measured in the urban background aerosol of Vienna, Austria. For several months, number size distributions between 13.22 nm and 929 nm were also measured with a scanning mobility particle spectrometer (SMPS). Activation ratios (i.e. CCN/CN ratios) were calculated and apparent activation diameters obtained by integrating the SMPS size distributions. Variations in all CCN parameters (concentration, activation ratio, apparent activation diameter) are quite large on timescales of days to weeks. Passages of fronts influenced CCN parameters. Concentrations decreased with the passage of a front. No significant differences were found for fronts from different sectors (for Vienna mainly north to west and south to east). CCN concentrations at 0.5% S ranged from 160 cm(-3) to 3600 cm(-3) with a campaign average of 820 cm(-3). Activation ratios were quite low (0.02-0.47, average: 0.13) and comparable to activation ratios found in other polluted regions (e.g. Cubison et al., 2008). Apparent activation diameters were found to be much larger (campaign average: 169 nm, range: (69-370) nm) than activation diameters for single-salt particles (around 50 nm depending on the salt). Contrary to CN concentrations, which are influenced by source patterns, CCN concentrations did not exhibit distinct diurnal patterns. Activation ratios showed diurnal variations counter-current to the variations of CN concentrations. PMID- 21977004 TI - Three-dimensional rigid multiphase networks providing high-temperature strength to cast AlSi10Cu5Ni1-2 piston alloys. AB - The three-dimensional (3-D) architecture of rigid multiphase networks present in AlSi10Cu5Ni1 and AlSi10Cu5Ni2 piston alloys in as-cast condition and after 4 h spheroidization treatment is characterized by synchrotron tomography in terms of the volume fraction of rigid phases, interconnectivity, contiguity and morphology. The architecture of both alloys consists of alpha-Al matrix and a rigid long-range 3-D network of Al(7)Cu(4)Ni, Al(4)Cu(2)Mg(8)Si(7), Al(2)Cu, Al(15)Si(2)(FeMn)(3) and AlSiFeNiCu aluminides and Si. The investigated architectural parameters of both alloys studied are correlated with room temperature and high-temperature (300 degrees C) strengths as a function of solution treatment time. The AlSi10Cu5Ni1 and AlSi10Cu5Ni2 alloys behave like metal matrix composites with 16 and 20 vol.% reinforcement, respectively. Both alloys have similar strengths in the as-cast condition, but the AlSi10Cu5Ni2 is able to retain ~15% higher high temperature strength than the AlSi10Cu5Ni1 alloy after more than 4 h of spheroidization treatment. This is due to the preservation of the 3-D interconnectivity and the morphology of the rigid network, which is governed by the higher degree of contiguity between aluminides and Si. PMID- 21977005 TI - Strong fragmentation processes driven by low energy electron attachment to various small perfluoroether molecules. AB - Negative ion formation in the three perfluoroethers (PFEs) diglyme (C(6)F(14)O(3)), triglyme (C(8)F(18)O(4)) and crownether (C(10)F(20)O(5)) is studied following electron attachment in the range from ~0 to 15 eV. All three compounds show intense low energy resonances at subexcitation energies (<3 eV) decomposing into a variety of negatively charged fragments. These fragment ions are generated via dissociative electron attachment (DEA), partly originating from sequential decompositions on the metastable (MUs) time scale as observed from the MIKE (metastable induced kinetic energy) scans. Only in perfluorocrownether a signal due to the non-decomposed parent anion is observed. Additional and comparatively weaker resonances are located in the energy range between ~10 and 17 eV which preferentially decompose into lighter ions. It is suggested that specific features of perfluoropolyethers (PFPEs) relevant in applications, e.g., the strong bonding to surfaces induced by UV radiation of the substrate or degradation of PFPE films in computer hard disc drives can be explained by their pronounced sensitivity towards low energy electrons. PMID- 21977006 TI - Erratum: to "Development of a Low-Cost SIA-Based Analyser for Water Samples". PMID- 21977009 TI - Exposure to the viral by-product dsRNA or Coxsackievirus B5 triggers pancreatic beta cell apoptosis via a Bim / Mcl-1 imbalance. AB - The rise in type 1 diabetes (T1D) incidence in recent decades is probably related to modifications in environmental factors. Viruses are among the putative environmental triggers of T1D. The mechanisms regulating beta cell responses to viruses, however, remain to be defined. We have presently clarified the signaling pathways leading to beta cell apoptosis following exposure to the viral mimetic double-stranded RNA (dsRNA) and a diabetogenic enterovirus (Coxsackievirus B5). Internal dsRNA induces cell death via the intrinsic mitochondrial pathway. In this process, activation of the dsRNA-dependent protein kinase (PKR) promotes eIF2alpha phosphorylation and protein synthesis inhibition, leading to downregulation of the antiapoptotic Bcl-2 protein myeloid cell leukemia sequence 1 (Mcl-1). Mcl-1 decrease results in the release of the BH3-only protein Bim, which activates the mitochondrial pathway of apoptosis. Indeed, Bim knockdown prevented both dsRNA- and Coxsackievirus B5-induced beta cell death, and counteracted the proapoptotic effects of Mcl-1 silencing. These observations indicate that the balance between Mcl-1 and Bim is a key factor regulating beta cell survival during diabetogenic viral infections. PMID- 21977007 TI - Corticostriatal circuit dysfunction in Huntington's disease: intersection of glutamate, dopamine and calcium. AB - Huntington's disease (HD) is a noncurable and progressive autosomal-dominant neurodegenerative disorder that results from a polyglutamine expansion in the amino-terminal region of the huntingtin protein. The generation of rodent HD models has revealed that cellular dysfunction, rather than cell death alone, occurs early in the disease progression, appearing even before overt symptom onset. Much evidence has now established that dysfunction of the corticostriatal circuit is key to HD symptomology. In this article, we summarize the most current findings that implicate glutamate, dopamine and calcium signaling in this system and discuss how they work in concert to disrupt corticostriatal function. In addition, we highlight therapeutic strategies related to altered corticostriatal signaling in HD. PMID- 21977010 TI - DNA-Platinum Thin Films for Use in Chemoradiation Therapy Studies. AB - Dry films of platinum chemotherapeutic drugs covalently bound to plasmid DNA (Pt DNA) represent a useful experimental model to investigate direct effects of radiation on DNA in close proximity to platinum chemotherapeutic agents, a situation of considerable relevance to understand the mechanisms underlying concomitant chemoradiation therapy. In the present paper we determine the optimum conditions for preparation of Pt-DNA films for use in irradiation experiments. Incubation conditions for DNA platination reactions have a substantial effect on the structure of Pt-DNA in the films. The quantity of Pt bound to DNA as a function of incubation time and temperature is measured by inductively coupled plasma mass spectroscopy. Our experiments indicate that chemical instability and damage to DNA in Pt-DNA samples increase when DNA platination occurs at 37( degrees )C for 24 hours, the condition which has been extensively used for in vitro studies. Platination of DNA for the formation of Pt-DNA films is optimal at room temperature for reaction times less than 2 hours. By increasing the concentration of Pt compounds relative to DNA and thus accelerating the rate of their mutual binding, it is possible to prepare Pt-DNA samples containing known concentrations of Pt while reducing DNA degradation caused by more lengthy procedures. PMID- 21977011 TI - 'If no one else stands up, you have to': a story of community participation and water in rural Guatemala. AB - BACKGROUND: Access to water is a right and a social determinant of health that should be provided by the state. However, when it comes to access to water in rural areas, the current trend is for communities to arrange for the service themselves through locally run projects. This article presents a narrative of a single community's process of participation in implementing and running a water project in the village of El Triunfo, Guatemala. METHODS: Using an ethnographic approach, we conducted a series of interviews with five village leaders, field visits, and participant observations in different meetings and activities of the community. FINDINGS: El Triunfo has had a long tradition of community participation, where it has been perceived as an important value. The village has a council of leaders who have worked together in various projects, although water has always been a priority. When it comes to participation, this community has achieved its goals when it collaborated with other stakeholders who provided the expertise and/or the funding needed to carry out a project. At the time of the study, the challenge was to develop a new phase of the water project with the help of other stakeholders and to maintain and sustain the tradition of participation by involving new generations in the process. DISCUSSION: This narrative focuses on the participation in this village's efforts to implement a water project. We found that community participation has substituted the role of the central and local governments, and that the collaboration between the council and other stakeholders has provided a way for El Triunfo to satisfy some of its demand for water. CONCLUSION: El Triunfo's case shows that for a participatory scheme to be successful it needs prolonged engagement, continued support, and successful experiences that can help to provide the kind of stable participatory practices that involves community members in a process of empowered decision making and policy implementation. PMID- 21977012 TI - Subunit Compensation and Plasticity of Synaptic GABA(A) Receptors Induced by Ethanol in alpha4 Subunit Knockout Mice. AB - There is considerable evidence that ethanol (EtOH) potentiates gamma-aminobutyric acid type A receptor (GABA(A)R) action, but only GABA(A)Rs containing delta subunits appear sensitive to low millimolar EtOH. The alpha4 and delta subunits co-assemble into GABA(A)Rs which are relatively highly expressed at extrasynaptic locations in the dentate gyrus where they mediate tonic inhibition. We previously demonstrated reversible- and time-dependent changes in GABA(A)R function and subunit composition in rats after single-dose EtOH intoxication. We concluded that early tolerance to EtOH occurs by over-activation and subsequent internalization of EtOH-sensitive extrasynaptic alpha4betadelta-GABA(A)Rs. Based on this hypothesis, any highly EtOH-sensitive GABA(A)Rs should be subject to internalization following exposure to suitably high EtOH doses. To test this, we studied the GABA(A)Rs in mice with a global deletion of the alpha4 subunit (KO). The dentate granule cells of these mice exhibited greatly reduced tonic currents and greatly reduced potentiation by acutely applied EtOH, whereas synaptic currents showed heightened sensitivity to low EtOH concentrations. The hippocampus of naive KO mice showed reduced delta subunit protein levels, but increased alpha2, and gamma2 levels compared to wild-type (WT) controls, suggesting at least partial compensation by these subunits in synaptic, highly EtOH-sensitive GABA(A)Rs of KO mice. In WT mice, cross-linking and Western blot analysis at 1 h after an EtOH challenge (3.5 g/kg, i.p.) revealed increased intracellular fraction of the alpha1, alpha4, and delta, but not alpha2, alpha5, or gamma2 subunits. By contrast, we observed significant internalization of alpha1, alpha2, delta, and gamma2 subunits after a similar EtOH challenge in KO mice. Synaptic currents from naive KO mice were more sensitive to potentiation by zolpidem (0.3 MUM, requiring alpha1/alpha2, inactive at alpha4/5 GABA(A)Rs) than those from naive WT mice. At 1 h after EtOH, synaptic currents of WT mice were unchanged, whereas those of KO mice were significantly less sensitive to zolpidem, suggesting decreases in functional alpha1/2betagamma GABA(A)Rs. These data further support our hypothesis that EtOH intoxication induces GABA(A)R plasticity via internalization of highly EtOH-sensitive GABA(A)Rs. PMID- 21977013 TI - Deoxyribozymes: new therapeutics to treat central nervous system disorders. AB - This mini-review focuses on a knockdown technology called deoxyribozymes, which has rarely been utilized in the field of neurobiology/neuroscience. Deoxyribozymes are catalytic DNA molecules, which are also entitled DNA enzyme or DNAzyme. This mini-review presents a description of their development, structure, function, and therapeutic application. In addition, information on siRNA, ribozymes, and antisense are given. Further information on two deoxyribozymes against c-Jun and xylosyltransferase (XT) mRNA are summarized of which the first is important to influence many neurological disorders and the last potentially treats spinal cord injuries (SCIs). In particular, insults to the central nervous system (CNS) such as SCI generate an inhibitory environment (lesion scar) at the injury site that prevents the endogenous and therapy-induced axonal regeneration and thereby limits repair strategies. Presently, there are no treatments available. Hence, deoxyribozymes provide an opportunity for new therapeutics that alter the inhibitory nature of the lesion scar and thus promote axonal growth in the injured spinal cord. When used cautiously and within the limits of its ability the deoxyribozyme technology holds promise to become a major contributing factor in repair strategies of the CNS. PMID- 21977014 TI - Modeling pharmacological clock and memory patterns of interval timing in a striatal beat-frequency model with realistic, noisy neurons. AB - In most species, the capability of perceiving and using the passage of time in the seconds-to-minutes range (interval timing) is not only accurate but also scalar: errors in time estimation are linearly related to the estimated duration. The ubiquity of scalar timing extends over behavioral, lesion, and pharmacological manipulations. For example, in mammals, dopaminergic drugs induce an immediate, scalar change in the perceived time (clock pattern), whereas cholinergic drugs induce a gradual, scalar change in perceived time (memory pattern). How do these properties emerge from unreliable, noisy neurons firing in the milliseconds range? Neurobiological information relative to the brain circuits involved in interval timing provide support for an striatal beat frequency (SBF) model, in which time is coded by the coincidental activation of striatal spiny neurons by cortical neural oscillators. While biologically plausible, the impracticality of perfect oscillators, or their lack thereof, questions this mechanism in a brain with noisy neurons. We explored the computational mechanisms required for the clock and memory patterns in an SBF model with biophysically realistic and noisy Morris-Lecar neurons (SBF-ML). Under the assumption that dopaminergic drugs modulate the firing frequency of cortical oscillators, and that cholinergic drugs modulate the memory representation of the criterion time, we show that our SBF-ML model can reproduce the pharmacological clock and memory patterns observed in the literature. Numerical results also indicate that parameter variability (noise) - which is ubiquitous in the form of small fluctuations in the intrinsic frequencies of neural oscillators within and between trials, and in the errors in recording/retrieving stored information related to criterion time - seems to be critical for the time-scale invariance of the clock and memory patterns. PMID- 21977015 TI - Hierarchical information-based clustering for connectivity-based cortex parcellation. AB - One of the most promising avenues for compiling connectivity data originates from the notion that individual brain regions maintain individual connectivity profiles; the functional repertoire of a cortical area ("the functional fingerprint") is closely related to its anatomical connections ("the connectional fingerprint") and, hence, a segregated cortical area may be characterized by a highly coherent connectivity pattern. Diffusion tractography can be used to identify borders between such cortical areas. Each cortical area is defined based upon a unique probabilistic tractogram and such a tractogram is representative of a group of tractograms, thereby forming the cortical area. The underlying methodology is called connectivity-based cortex parcellation and requires clustering or grouping of similar diffusion tractograms. Despite the relative success of this technique in producing anatomically sensible results, existing clustering techniques in the context of connectivity-based parcellation typically depend on several non-trivial assumptions. In this paper, we embody an unsupervised hierarchical information-based framework to clustering probabilistic tractograms that avoids many drawbacks offered by previous methods. Cortex parcellation of the inferior frontal gyrus together with the precentral gyrus demonstrates a proof of concept of the proposed method: The automatic parcellation reveals cortical subunits consistent with cytoarchitectonic maps and previous studies including connectivity-based parcellation. Further insight into the hierarchically modular architecture of cortical subunits is given by revealing coarser cortical structures that differentiate between primary as well as premotoric areas and those associated with pre-frontal areas. PMID- 21977016 TI - Modeling the connectome of a simple spinal cord. AB - In this paper we develop a computational model of the anatomy of a spinal cord. We address a long-standing ambition of neuroscience to understand the structure function problem by modeling the complete spinal cord connectome map in the 2-day old hatchling Xenopus tadpole. Our approach to modeling neuronal connectivity is based on developmental processes of axon growth. A simple mathematical model of axon growth allows us to reconstruct a biologically realistic connectome of the tadpole spinal cord based on neurobiological data. In our model we distribute neuron cell bodies and dendrites on both sides of the body based on experimental measurements. If growing axons cross the dendrite of another neuron, they make a synaptic contact with a defined probability. The total neuronal network contains ~1,500 neurons of six cell-types with a total of ~120,000 connections. The anatomical model contains random components so each repetition of the connectome reconstruction procedure generates a different neuronal network, though all share consistent features such as distributions of cell bodies, dendrites, and axon lengths. Our study reveals a complex structure for the connectome with many interesting specific features including contrasting distributions of connection length distributions. The connectome also shows some similarities to connectivity graphs for other animals such as the global neuronal network of C. elegans. In addition to the interesting intrinsic properties of the connectome, we expect the ability to grow and analyze a biologically realistic spinal cord connectome will provide valuable insights into the properties of the real neuronal networks underlying simple behavior. PMID- 21977017 TI - Impaired ventilatory and thermoregulatory responses to hypoxic stress in newborn phox2b heterozygous knock-out mice. AB - The Phox2b genesis necessary for the development of the autonomic nervous system, and especially, of respiratory neuronal circuits. In the present study, we examined the role of Phox2b in ventilatory and thermoregulatory responses to hypoxic stress, which are closely related in the postnatal period. Hypoxic stress was generated by strong thermal stimulus, combined or not with reduced inspired O(2). To this end, we exposed 6-day-old Phox2b(+/-) pups and their wild-type littermates (Phox2b(+/+)) to hypoxia (10% O(2)) or hypercapnia (8% CO(2)) under thermoneutral (33 degrees C) or cold (26 degrees C) conditions. We found that Phox2b(+/-) pups showed less normoxic ventilation (V(E)) in the cold than Phox2b(+/+) pups. Phox2b(+/-) pups also showed lower oxygen consumption (VO(2)) in the cold, reflecting reduced thermogenesis and a lower body temperature. Furthermore, while the cold depressed ventilatory responses to hypoxia and hypercapnia in both genotype groups, this effect was less pronounced in Phox2b(+/ ) pups. Finally, because serotonin (5-HT) neurons are pivotal to respiratory and thermoregulatory circuits and depend on Phox2b for their differentiation, we studied 5-HT metabolism using high pressure liquid chromatography, and found that it was altered in Phox2b(+/-) pups. We conclude that Phox2b haploinsufficiency alters the ability of newborns to cope with metabolic challenges, possibly due to 5-HT signaling impairments. PMID- 21977018 TI - ERP Evidence for Scarce Rule Representation in Older Adults Following Short, but Not Long Preparatory Intervals. AB - The focus of the present study was to examine the cognitive processes comprising advance preparation - rule representation, task-set updating, and task-set reconfiguration - in young (20-25 years) and older adults (61-83 years). Specifically, this study aimed at further characterizing age-related differences in advance preparation, and evaluating how additional time to prepare might reduce behavioral costs in older adults. In line with previous findings, reaction time mixing costs were slightly larger for older compared to young adults, whereas behavioral switch costs were age-invariant. Following short preparation (600 ms), smaller antero-frontal event-related potential (ERP) correlates of rule representation were associated with pronounced congruency costs in older adults. Centro-parietal ERP correlates of task-set updating and task-set reconfiguration were not delayed, but smaller in magnitude for older compared to young adults. Longer preparation (1200 ms) enabled older adults to re-activate relevant task rules, as evident in reduced congruency costs, and temporally sustained ERP correlates of task-set updating and rule representation well beyond 600 ms. Age invariant switch costs appear related to additional, potentially compensatory frontal activity recruited by older adults to overcome difficulties in task-set reconfiguration. PMID- 21977019 TI - There is no Such Thing as Attention. AB - Given that the core issues of attention research have been recognized for millenia, we do not know as much about attention as we should. I argue that the reasons for this failure are (1) we create spurious dichotomies, (2) we reify attention, treating it as a cause, when it is an effect, and (3) we equate a collection of facts with a theory. In order to correct these errors, we need a new technical vocabulary that allows for attentional effects to be continuously distributed, rather than merely present or absent, and that provides a basis for quantitative behavioral predictions that map onto neural substrates. The terminology of the Bayesian decision process has already proved useful for structuring conceptual discussions in other psychological domains, such as perception and decision making under uncertainty, and it had demonstrated early success in the domain of attention. By rejecting a reified, causal conception of attention, in favor of theories that produce attentional effects as consequences, psychologists will be able to conduct more definitive experiments. Such conceptual advances will then enhance the productivity of neuroscientists by allowing them to concentrate their data collection efforts on the richest soil. PMID- 21977020 TI - True 4D Image Denoising on the GPU. AB - The use of image denoising techniques is an important part of many medical imaging applications. One common application is to improve the image quality of low-dose (noisy) computed tomography (CT) data. While 3D image denoising previously has been applied to several volumes independently, there has not been much work done on true 4D image denoising, where the algorithm considers several volumes at the same time. The problem with 4D image denoising, compared to 2D and 3D denoising, is that the computational complexity increases exponentially. In this paper we describe a novel algorithm for true 4D image denoising, based on local adaptive filtering, and how to implement it on the graphics processing unit (GPU). The algorithm was applied to a 4D CT heart dataset of the resolution 512 * 512 * 445 * 20. The result is that the GPU can complete the denoising in about 25 minutes if spatial filtering is used and in about 8 minutes if FFT-based filtering is used. The CPU implementation requires several days of processing time for spatial filtering and about 50 minutes for FFT-based filtering. The short processing time increases the clinical value of true 4D image denoising significantly. PMID- 21977021 TI - Cortical evoked potentials in children of diabetic mothers. AB - Type 1 diabetic mothers' infants show a delay of visual evoked potential (VEP) significantly related to some parameters of poor metabolic control during pregnancy. In the present paper we analyzed the characteristics of VEPs and somatosensory evoked potentials (SEPs) recorded in 16 three-year-old type 1 diabetic mothers' children (DMC). Compared with controls (23 nondiabetic mothers' healthy matched children), DMC showed significantly delayed mean latency of VEP (P2) and SEP (P22). In 3 cases (19%), we found pathological responses (+3 SD from the mean value of controls) of VEPs and SEPs. At the age of 3 years, the offspring of type 1 diabetic mothers showed delay of cortical evoked responses in both visual and somatosensory systems. PMID- 21977022 TI - Differential changes of aorta and carotid vasodilation in type 2 diabetic GK and OLETF rats: paradoxical roles of hyperglycemia and insulin. AB - We investigated large vessel function in lean Goto-Kakizaki diabetic rats (GK) and Otsuka Long-Evans Tokushima Fatty diabetic rats (OLETF) with possible roles of hyperglycemia/hyperosmolarity and insulin. Both young and old GK showed marked hyperglycemia with normal insulin level and well-preserved endothelium-dependent and endothelium-independent vasodilation in aorta and carotid artery. There were significant elevations in endothelial/inducible nitric oxide synthase (eNOS/iNOS) and inducible/constitutive heme oxygenase (HO-1/HO-2) in GK. The endothelium dependent vasodilation in GK was inhibited partly by NOS blockade and completely by simultaneous blocking of HO and NOS. In contrast, OLETF showed hyperinsulinemia and mild hyperglycemia but significant endothelium dysfunction beginning at early ages with concomitantly reduced eNOS. Insulin injection corrected hyperglycemia in GK but induced endothelium dysfunction and intima hyperplasia. Hyperglycemia/hyperosmolarity in vitro enhanced vessel eNOS/HO. We suggest that hyperinsulinemia plays a role in endothelium dysfunction in obese diabetic OLETF, while hyperglycemia/hyperosmolarity-induced eNOS/HO upregulation participates in the adaptation of endothelium function in lean diabetic GK. PMID- 21977023 TI - Guards and culprits in the endoplasmic reticulum: glucolipotoxicity and beta-cell failure in type II diabetes. AB - The endoplasmic reticulum (ER) is a cellular organelle responsible for multiple important cellular functions including the biosynthesis and folding of newly synthesized proteins destined for secretion, such as insulin. The ER participates in all branches of metabolism, linking nutrient sensing to cellular signaling. Many pathological and physiological factors perturb ER function and induce ER stress. ER stress triggers an adaptive signaling cascade, called the unfolded protein response (UPR), to relieve the stress. The failure of the UPR to resolve ER stress leads to pathological conditions such as beta-cell dysfunction and death, and type II diabetes. However, much less is known about the fine details of the control and regulation of the ER response to hyperglycemia (glucotoxicity), hyperlipidemia (lipotoxicity), and the combination of both (glucolipotoxicity). This paper considers recent insights into how the response is regulated, which may provide clues into the mechanism of ER stress-mediated beta-cell dysfunction and death during the progression of glucolipotoxicity induced type II diabetes. PMID- 21977025 TI - Differential expression of three flavanone 3-hydroxylase genes in grains and coleoptiles of wheat. AB - Flavonoid pigments are known to accumulate in red grains and coleoptiles of wheat and are synthesized through the flavonoid biosynthetic pathway. Flavanone 3 hydroxylase (F3H) is a key enzyme at a diverging point of the flavonoid pathway leading to production of different pigments: phlobaphene, proanthocyanidin, and anthocyanin. We isolated three F3H genes from wheat and examined a relationship between their expression and tissue pigmentation. Three F3Hs are located on the telomeric region of the long arm of chromosomes 2A, 2B, and 2D, respectively, designated as F3H-A1, F3H-B1, and F3H-D1. The telomeric regions of the long arms of the chromosomes of homoeologous group 2 of wheat showed a syntenic relationship to the telomeric region of the long arm of rice chromosome 4, on which rice F3H gene was also located. All three genes were highly activated in the red grains and coleoptiles and appeared to be controlled by flavonoid regulators in each tissue. PMID- 21977026 TI - Swallowing in Parkinson Patients versus Healthy Controls: Reliability of Measurements in Videofluoroscopy. AB - Objective. To determine and describe the pathophysiological aspects of oropharyngeal swallowing in patients with Parkinson's disease more accurately, a pilot study of qualitative as well as quantitative parameters of swallowing was performed using videofluoroscopy (VFS). Methods. Ten patients with a diagnosis of idiopathic Parkinson's disease having dysphagic complaints and ten healthy age- and gender-matched control subjects underwent a standardized videofluoroscopic swallowing protocol. Information on the swallowing function was derived from temporal, spatial, and descriptive visuoperceptual parameters. Intra- and interrater reliability was calculated. Results. No significant differences were found between Parkinson patients and healthy control subjects for the majority of the reliable variables. Conclusions. It was concluded that swallowing function seemed to be preserved in the early stages of Parkinson's disease. Furthermore, the reliability of many quantitative as well as qualitative swallowing parameters proved insufficient, raising questions about the interpretation of study outcomes in videofluoroscopy. PMID- 21977027 TI - Predictive value of positive surgical margins after radical prostatectomy for lymph node metastasis in locally advanced prostate carcinoma. AB - Introduction. Suspected locally advanced prostate carcinoma shows lymph node involvement in a high percentage of cases. For a long time, such patients were not radically prostatectomised. In recent years, however, this viewpoint has changed. Material and Methods. We analysed a single-centre series of 34 patients with suspected locally advanced prostate cancer to establish predictive parameters for lymph node metastasis. All patients underwent radical prostatectomy between 2007 and 2010. Results. Of the 34 patients, 26% showed pathological stage T3a, 59% pT3b, and 15% pT4. Median preoperative PSA level was 25 ng/mL, and five patients had had neoadjuvant antihormonal treatment. Positive margins were found in 76% of patients. Patients without neoadjuvant treatment showed it in 79%, and after preoperative antihormonal treatment the rate was 60%. Positive margins were associated with lymph node involvement in 85% of cases, complete resection was associated only in 50% of cases. Conclusions. Positive surgical margins play an important predictive role when estimating lymph node involvement in patients with locally advanced prostate carcinoma. Neoadjuvant antihormonal therapy is associated with a relevant reduction in the rate of positive margins but not with the rate of lymph node metastasis. As such, a combination of antihormonal and surgical treatment should be considered. PMID- 21977024 TI - Cardiac insulin resistance and microRNA modulators. AB - Cardiac insulin resistance is a metabolic and functional disorder that is often associated with obesity and/or the cardiorenal metabolic syndrome (CRS), and this disorder may be accentuated by chronic alcohol consumption. In conditions of over nutrition, increased insulin (INS) and angiotensin II (Ang II) activate mammalian target for rapamycin (mTOR)/p70 S6 kinase (S6K1) signaling, whereas chronic alcohol consumption inhibits mTOR/S6K1 activation in cardiac tissue. Although excessive activation of mTOR/S6K1 induces cardiac INS resistance via serine phosphorylation of INS receptor substrates (IRS-1/2), it also renders cardioprotection via increased Ang II receptor 2 (AT2R) upregulation and adaptive hypertrophy. In the INS-resistant and hyperinsulinemic Zucker obese (ZO) rat, a rodent model for CRS, activation of mTOR/S6K1signaling in cardiac tissue is regulated by protective feed-back mechanisms involving mTOR<->AT2R signaling loop and profile changes of microRNA that target S6K1. Such regulation may play a role in attenuating progressive heart failure. Conversely, alcohol-mediated inhibition of mTOR/S6K1, down-regulation of INS receptor and growth-inhibitory mir-200 family, and upregulation of mir-212 that promotes fetal gene program may exacerbate CRS-related cardiomyopathy. PMID- 21977028 TI - Systematically controlling for the influence of age, sex, hertz and time post whole-body vibration exposure on four measures of physical performance in community-dwelling older adults: a randomized cross-over study. AB - Though popular, there is little agreement on what whole-body vibration (WBV) parameters will optimize performance. This study aimed to clarify the effects of age, sex, hertz and time on four physical function indicators in community dwelling older adults (N = 32). Participants were exposed to 2 min WBV per session at either 2 Hz or 26 Hz and outcome measures were recorded at 2, 20 and 40 min post-WBV. Timed get up-and-go and chair sit-and-reach performances improved post-WBV for both sexes, were significantly different between 2 Hz and 26 Hz treatments (P <= 0.05) and showed statistically significant interactions between age and gender (P <= 0.01). Counter movement jump and timed one-legged stance performances showed a similar but non-significant response to 2 Hz and 26 Hz treatments, though male subjects showed a distinct trended response. Age and gender should be statistically controlled and both 2 Hz and 26 Hz exert a treatment effect. PMID- 21977029 TI - The role of prophylactic central neck dissection in differentiated thyroid carcinoma: issues and controversies. AB - Prophylactic central neck dissection (pCND) in differentiated thyroid carcinoma (DTC) is one of the most controversial surgical subjects in recent times. To date, there is little evidence to support the practice of pCND in patients with DTC undergoing total thyroidectomy. Although the recently revised American Thyroid Association (ATA) guideline has clarified many inconsistencies regarding pCND and has recommended pCND in "high-risk" patients, many issues and controversies surrounding the subject of pCND in DTC remain. The recent literature has revealed an insignificant trend toward lower recurrence rate in patients with DTC who undergo total thyroidectomy and pCND than those who undergo total thyroidectomy alone. However, this was subjected to biases, and there are concerns whether pCND should be performed by all surgeons who manage DTC because of increased surgical morbodity. Performing a unilateral pCND may be better than a bilateral pCND given its lower surgical morbidity. Further studies in this controversial subject are much needed. PMID- 21977030 TI - Antimyeloma Effects of the Heat Shock Protein 70 Molecular Chaperone Inhibitor MAL3-101. AB - Multiple myeloma (MM) is the second most common hematologic malignancy and remains incurable, primarily due to the treatment-refractory/resistant nature of the disease. A rational approach to this compelling challenge is to develop new drugs that act synergistically with existing effective agents. This approach will reduce drug concentrations, avoid treatment resistance, and also improve treatment effectiveness by targeting new and nonredundant pathways in MM. Toward this goal, we examined the antimyeloma effects of MAL3-101, a member of a new class of non-ATP-site inhibitors of the heat shock protein (Hsp) 70 molecular chaperone. We discovered that MAL3-101 exhibited antimyeloma effects on MM cell lines in vitro and in vivo in a xenograft plasmacytoma model, as well as on primary tumor cells and bone marrow endothelial cells from myeloma patients. In combination with a proteasome inhibitor, MAL3-101 significantly potentiated the in vitro and in vivo antimyeloma effects. These data support a preclinical rationale for small molecule inhibition of Hsp70 function, either alone or in combination with other agents, as an effective therapeutic strategy for MM. PMID- 21977031 TI - Serum monocyte chemoattractant protein-1 in pancreatic cancer. AB - Background/Aims. Pancreatic ductal adenocarcinoma (PDA) has etiological association with chronic inflammation. Elevated circulating levels of inflammatory mediators, such as monocyte chemoattractant protein-1 (MCP-1), are found in obese individuals. We hypothesized that serum MCP-1 levels are elevated in obese PDA patients. Methods. ELISA was used to analyze MCP-1 serum levels in PDA (n = 62) and intraductal papillary mucinous neoplasms (IPMN) (n = 27). Recursive partitioning statistical analysis investigated the relationship between log MCP-1 and clinicopathological parameters. Results. Log MCP-1 values were significantly (P < 0.05) elevated in patients with BMI >= 37.5. In patients with BMI < 37.5, average log MCP-1 values were significantly elevated in PDA patients when compared to IPMN patients. Within the IPMN group, higher log MCP-1 levels correlated with increased age. Recursive partitioning analysis of IPMN versus PDA revealed a strategy of predicting characteristics of patients who are more likely to have cancer. This strategy utilizes log MCP-1 as the primary factor and also utilizes smoking status, gender, and age. Conclusion. MCP-1 is a promising biomarker in pancreatic cancer. The potential of using MCP-1 to distinguish PDA from IPMN patients must be studied in larger populations to validate and demonstrate its eventual clinical utility. PMID- 21977032 TI - Bone Marrow Suppression by c-Kit Blockade Enhances Tumor Growth of Colorectal Metastases through the Action of Stromal Cell-Derived Factor-1. AB - Background. Mobilization of c-Kit(+) hematopoietic cells (HCs) contributes to tumor vascularization. Whereas survival and proliferation of HCs are regulated by binding of the stem cell factor to its receptor c-Kit, migration of HCs is directed by stromal cell-derived factor (SDF)-1. Therefore, targeting migration of HCs provides a promising new strategy of anti-tumor therapy. Methods. BALB/c mice (n = 16) were pretreated with an anti-c-Kit antibody followed by implantation of CT26.WT-GFP colorectal cancer cells into dorsal skinfold chambers. Animals (n = 8) additionally received a neutralizing anti-SDF-1 antibody. Animals (n = 8) treated with a control antibody served as controls. Investigations were performed using intravital fluorescence microscopy, immunohistochemistry, flow cytometry and western blot analysis. Results. Blockade of c-Kit significantly enhanced tumor cell engraftment compared to controls due to stimulation of tumor cell proliferation and invasion without markedly affecting tumor vascularization. C-Kit blockade significantly increased VEGF and CXCR4 expression within the growing tumors. Neutralization of SDF-1 completely antagonized this anti-c-Kit-associated tumor growth by suppression of tumor neovascularization, inhibition of tumor cell proliferation and reduction of muscular infiltration. Conclusion. Our study indicates that bone marrow suppression via anti-c-Kit pretreatment enhances tumor cell engraftment of colorectal metastases due to interaction with the SDF-1/CXCR4 pathway which is involved in HC-mediated tumor angiogenesis. PMID- 21977034 TI - Predicting the Kinetic Properties Associated with Redox Imbalance after Oxidative Crisis in G6PD-Deficient Erythrocytes: A Simulation Study. AB - It is well known that G6PD-deficient individuals are highly susceptible to oxidative stress. However, the differences in the degree of metabolic alterations among patients during an oxidative crisis have not been extensively studied. In this study, we applied mathematical modeling to assess the metabolic changes in erythrocytes of various G6PD-deficient patients during hydrogen peroxide- (H(2)O(2)-) induced perturbation and predict the kinetic properties that elicit redox imbalance after exposure to an oxidative agent. Simulation results showed a discrepancy in the ability to restore regular metabolite levels and redox homeostasis among patients. Two trends were observed in the response of redox status (GSH/GSSG) to oxidative stress, a mild decrease associated with slow recovery and a drastic decline associated with rapid recovery. The former was concluded to apply to patients with severe clinical symptoms. Low V(max) and high K(mG6P) of G6PD were shown to be kinetic properties that enhance consequent redox imbalance. PMID- 21977035 TI - The Effect of Sub-MIC beta-Lactam Antibiotic Exposure of Pseudomonas aeruginosa Strains from People with Cystic Fibrosis in a Desiccation Survival Model. AB - Prior to modern typing methods, cross-infection of P. aeruginosa between people with cystic fibrosis (CF) was felt to be rare. Recently a number of studies have demonstrated the presence of clonal strains of P. aeruginosa infecting people with CF. The aim of this study was to determine whether strains of P. aeruginosa demonstrated differences in resistance to desiccation and whether preincubation in subminimum inhibitory concentrations (MICs) of beta-lactam affected desiccation resistance. The experimental data were modelled to a first-order decay model and a Weibull decay model using least squares nonlinear regression. The Weibull model was the preferred model for the desiccation survival. The presence of a mucoid phenotype promoted desiccation survival. Preincubation with antibiotics did not have a consistent effect on the strains of P. aeruginosa. Meropenem reduced desiccation resistance, whereas ceftazidime had much less effect on the strains studied. PMID- 21977033 TI - Tumor angiogenesis as a target for dietary cancer prevention. AB - Between 2000 and 2050, the number of new cancer patients diagnosed annually is expected to double, with an accompanying increase in treatment costs of more than $80 billion over just the next decade. Efficacious strategies for cancer prevention will therefore be vital for improving patients' quality of life and reducing healthcare costs. Judah Folkman first proposed antiangiogenesis as a strategy for preventing dormant microtumors from progressing to invasive cancer. Although antiangiogenic drugs are now available for many advanced malignancies (colorectal, lung, breast, kidney, liver, brain, thyroid, neuroendocrine, multiple myeloma, myelodysplastic syndrome), cost and toxicity considerations preclude their broad use for cancer prevention. Potent antiangiogenic molecules have now been identified in dietary sources, suggesting that a rationally designed antiangiogenic diet could provide a safe, widely available, and novel strategy for preventing cancer. This paper presents the scientific, epidemiologic, and clinical evidence supporting the role of an antiangiogenic diet for cancer prevention. PMID- 21977036 TI - Dermatophyte virulence factors: identifying and analyzing genes that may contribute to chronic or acute skin infections. AB - Dermatophytes are prevalent causes of cutaneous mycoses and, unlike many other fungal pathogens, are able to cause disease in immunocompetent individuals. They infect keratinized tissue such as skin, hair, and nails, resulting in tinea infections, including ringworm. Little is known about the molecular mechanisms that underlie the ability of these organisms to establish and maintain infection. The recent availability of genome sequence information and improved genetic manipulation have enabled researchers to begin to identify and study the role of virulence factors of dermatophytes. This paper will summarize our current understanding of dermatophyte virulence factors and discuss future directions for identifying and testing virulence factors. PMID- 21977038 TI - Skin autofluorescence, as marker of accumulation of advanced glycation endproducts and of cumulative metabolic stress, is not increased in patients with systemic sclerosis. AB - Objective. To investigate whether advanced glycation endproducts (AGEs) in the skin are increased in patients with systemic sclerosis (SSc) and are related to the presence of disease-related and traditional cardiovascular risk factors. Methods. Skin autofluorescence, as a measure for the accumulation of AGEs, was assessed by measuring UV-A light excitation-emission matrices (AF-EEMS) in 41 SSc patients and 41 age- and sex-matched controls. Traditional cardiovascular risk factors and disease-related risk factors were recorded. Results. Skin AF-EEMS did not differ between SSc patients and controls (1.68 +/- 0.58 a.u. versus 1.63 +/- 0.41 a.u., P = 0.684). Skin AF-EEMS in SSc patients was associated with levels of CRP (r = 0.44, P = 0.004), Medsger's severity scale (r = 0.45, P = 0.006), and use of agents intervening in the renin-angiotensin system (r = 0.33, P = 0.027). When analysing SSc patients and controls together, in multivariate analysis, only age and use of agents intervening in the renin-angiotensin system were independently associated with AF-EEMS. Conclusion. These data demonstrate that skin AGEs are not increased in SSc patients. PMID- 21977039 TI - Parental Knowledge, Attitudes, and Behaviours towards Human Papillomavirus Vaccination for Their Children: A Systematic Review from 2001 to 2011. AB - Objectives. A systematic review of parental surveys about HPV and/or child HPV vaccination to understand parental knowledge, attitudes, and behaviour before and after FDA approval of the quadrivalent HPV vaccine and the bivalent HPV vaccine. Search Strategy. Searches were conducted using electronic databases limited to published studies between 2001 and 2011. Findings. The percentage of parents who heard about HPV rose over time (from 60% in 2005 to 93% in 2009), as did their appreciation for the HPV infection and cervical cancer link (from 70% in 2003 to 91% in 2011). During the FDA approval, there was a stronger vaccine awareness but it has waned. The same pattern is seen with parents whose children received the HPV vaccine (peak at 84% in 2010 and now 36% in 2011) or the intention to vaccinate (peak at 80% in 2008 and now 41% in 2011). Conclusions. Parents had safety concerns and wanted more information their physician from to recommend and to confidently HPV vaccinate their children. PMID- 21977037 TI - Protein Glycosylation in Aspergillus fumigatus Is Essential for Cell Wall Synthesis and Serves as a Promising Model of Multicellular Eukaryotic Development. AB - Glycosylation is a conserved posttranslational modification that is found in all eukaryotes, which helps generate proteins with multiple functions. Our knowledge of glycosylation mainly comes from the investigation of the yeast Saccharomyces cerevisiae and mammalian cells. However, during the last decade, glycosylation in the human pathogenic mold Aspergillus fumigatus has drawn significant attention. It has been revealed that glycosylation in A. fumigatus is crucial for its growth, cell wall synthesis, and development and that the process is more complicated than that found in the budding yeast S. cerevisiae. The present paper implies that the investigation of glycosylation in A. fumigatus is not only vital for elucidating the mechanism of fungal cell wall synthesis, which will benefit the design of new antifungal therapies, but also helps to understand the role of protein glycosylation in the development of multicellular eukaryotes. This paper describes the advances in functional analysis of protein glycosylation in A. fumigatus. PMID- 21977040 TI - Primary vulval rhabdoid tumor in an adult: a case report, immunohistochemical profile and literature review. AB - We report a rare case of primary vulval rhabdoid tumor in an adult. The diagnosis was confirmed using the recently emerging INI1/BAF47 immunostain. We also demonstrate the expression of ER and PR hormonal receptors by the tumor cells. PMID- 21977041 TI - Induced pluripotent stem cells in cardiovascular medicine. AB - Induced pluripotent stem (iPS) cells are generated by reprogramming human somatic cells through the forced expression of several embryonic stem (ES) cell-specific transcription factors. The potential of iPS cells is having a significant impact on regenerative medicine, with the promise of infinite self-renewal, differentiation into multiple cell types, and no problems concerning ethics or immunological rejection. Human iPS cells are currently generated by transgene introduction principally through viral vectors, which integrate into host genomes, although the associated risk of tumorigenesis is driving research into nonintegration methods. Techniques for pluripotent stem cell differentiation and purification to yield cardiomyocytes are also advancing constantly. Although there remain some unsolved problems, cardiomyocyte transplantation may be a reality in the future. After those problems will be solved, applications of human iPS cells in human cardiovascular regenerative medicine will be envisaged for the future. Furthermore, iPS cell technology has generated new human disease models using disease-specific cells. This paper summarizes the progress of iPS cell technology in cardiovascular research. PMID- 21977042 TI - Efficient non-viral integration and stable gene expression in multipotent adult progenitor cells. AB - Non-viral integrating systems, PhiC31 phage integrase (phiC31), and Sleeping Beauty transposase (SB), provide an effective method for ex vivo gene delivery into cells. Here, we used a plasmid-encoding GFP and neomycin phosphotransferase along with recognition sequences for both phiC31 and SB integrating systems to demonstrate that both systems effectively mediated integration in cultured human fibroblasts and in rat multipotent adult progenitor cells (rMAPC). Southern blot analysis of G418-resistant rMAPC clones showed a 2-fold higher number of SB mediated insertions per clone compared to phiC31. Sequence identification of chromosomal junction sites indicated a random profile for SB-mediated integrants and a more restricted profile for phiC31 integrants. Transgenic rMAPC generated with both systems maintained their ability to differentiate into liver and endothelium albeit with marked attenuation of GFP expression. We conclude that both SB and phiC31 are effective non-viral integrating systems for genetic engineering of MAPC in basic studies of stem cell biology. PMID- 21977043 TI - Hepatic differentiation of murine disease-specific induced pluripotent stem cells allows disease modelling in vitro. AB - Direct reprogramming of somatic cells into pluripotent cells by retrovirus mediated expression of OCT4, SOX2, KLF4, and C-MYC is a promising approach to derive disease-specific induced pluripotent stem cells (iPSCs). In this study, we focused on three murine models for metabolic liver disorders: the copper storage disorder Wilson's disease (toxic-milk mice), tyrosinemia type 1 (fumarylacetoacetate-hydrolase deficiency, FAH(-/-) mice), and alpha1-antitrypsin deficiency (PiZ mice). Colonies of iPSCs emerged 2-3 weeks after transduction of fibroblasts, prepared from each mouse strain, and were maintained as individual iPSC lines. RT-PCR and immunofluorescence analyses demonstrated the expression of endogenous pluripotency markers. Hepatic precursor cells could be derived from these disease-specific iPSCs applying an in vitro differentiation protocol and could be visualized after transduction of a lentiviral albumin-GFP reporter construct. Functional characterization of these cells allowed the recapitulation of the disease phenotype for further studies of underlying molecular mechanisms of the respective disease. PMID- 21977044 TI - Developmental and cognitive characteristics of "high-level potentialities" (highly gifted) children. AB - This study covers the interesting field of the development in gifted children which is often neglected in pediatrics because psychomotor development data are still rare, since "gifted" children are generally noticed towards the end of their primary schooling by IQ measurement. Developmental studies have shown the evidence from several fields that children identified as "high-level potentialities" or "intellectually gifted" develop sensory, locomotor, neuropsychological, and language skills earlier than typically expected. The hypothesis is offered that the earlier development originates from biological processes affecting the physical development of the brain and in turn even intellectual abilities are developed earlier, potentially allowing for advanced development. Further it is discussed how these developmental advances interact with the social environment and in certain circumstances may entail increased risk for developing socioemotional difficulties and learning disabilities that often go unaddressed due to the masking by the advance intellectual abilities. PMID- 21977045 TI - High prevalence of sinusitis in children with henoch-schonlein purpura. AB - We evaluated the prevalence and the types of infectious foci in oral as well as ear, nose, and throat diseases, and we examined incidence of renal involvement with active treatment for focal infection in children with Henoch-Schonlein Purpura. A total of 96 children who presented at Aichi Children's Health and Medical Center and were diagnosed as having HSP were evaluated for infectious foci in the ear, nose, throat, and oral cavities. Seventy-one of 96 children (74.0%) had some type of infectious lesion, such as sinusitis or tonsillitis, and the prevalence of sinusitis was the highest (51 cases, 53.7%). In 44 HSP patients without renal involvement at the first examination, the incidence of nephritis was lower (13.6%) than in previous reports (17-54%) due to our aggressive intervention for infectious foci. PMID- 21977046 TI - Effects of voluntary running in the female mice lateral septum on BDNF and corticotropin-releasing factor receptor 2. AB - Voluntary physical activities are known to modulate anxiety and depressive/like behaviors in both animals and humans. Brain derived neurotrophic factor (BDNF), has been reported to be elevated following exercise. BDNF, as well as type 2 corticotrophin releasing factor receptor (CRFR) 2, has been shown to mediate anxiety-like behavior. In the present study we examined the effects of long-term voluntary exercise on the transcripts for BDNF and CRFR2 in the lateral septum (LS) and for CRF in the central amygdala (CeA) in female mice. Thus, increased activity of CRF in the CeA is associated with anxiety-like behavior. Quantitative RT-PCR was employed to measure levels of mRNA in punch biopsies from LS and CeA. In addition, measurements of the concentration of corticosterone and leptin in plasma were employed. In the LS, we found a three-fold increase of BDNF mRNA (P < 0.05) but no significant change in CRFR2 mRNA. No changes in CRF in the amygdala were observed but we found a decrease in the levels of plasma corticosterone. Plasma leptin and the weight of perigonadal fat pads were decreased following exercise. In conclusion, these data show that BDNF gene expression in the LS is influenced by long-term exercise in females but not CRFR2. PMID- 21977047 TI - Prevalence of influenza A (H1N1) seropositivity in unvaccinated healthcare workers in Scotland at the height of the global pandemic. AB - BACKGROUND: We set out to identify the level of previous exposure to influenza A (H1N1) in unvaccinated healthcare workers (HCWs) at the peak of the pandemic outbreak in the UK, with control samples collected prior to the outbreak. METHODS: Cross-sectional study (seroprevalence assessed before and at pandemic peak, with questionnaire data collected at peak of outbreak) in HCWs in Scotland. RESULTS: The prevalence of seropositivity in 493 HCWs at pandemic peak was 10.3%, which was higher than the prepandemic level by 3.7 percentage points (95% CI 0.3% to 7.3%, P = 0.048). Seropositivity rates for frontline and nonfrontline HCWs were similar. CONCLUSION: At pandemic peak, only 10.3% of HCWs were seropositive for influenza A (H1N1), so the great majority were still susceptible to infection at the introduction of the vaccination programme. Few studies have reported on seroprevalence in unvaccinated and asymptomatic participants, so our findings may have relevance to the wider population. PMID- 21977048 TI - Risk factors for colonization of E. coli in Atlantic Bottlenose Dolphins (Tursiops truncatus) in the Indian River Lagoon, Florida. AB - Opportunistic pathogens related to degradation in water quality are of concern to both wildlife and public health. The objective of this study was to identify spatial, temporal, and environmental risk factors for E. coli colonization among Atlantic bottlenose dolphins (Tursiops truncatus) inhabiting the Indian River Lagoon (IRL), FL between 2003 and 2007. Age, gender, capture location, coastal human population density, proximity of sewage treatment plants, number of septic tanks, cumulative precipitation 48 hrs and 30 days prior to capture, salinity, and water temperature were analyzed as potential risk factors. Highest E. coli colonization rates occurred in the northern segments of the IRL. The risk of E. coli colonization was the highest among the youngest individuals, in counties with the highest cumulative rainfall 48 hrs and in counties with the highest number of septic systems during the year of capture. The prevalence of colonization was the highest during 2004, a year during which multiple hurricanes hit the coast of Florida. Septic tanks, in combination with weather-related events suggest a possible pathway for introduction of fecal coliforms into estuarine ecosystems. The ability of E. coli and related bacteria to act as primary pathogens or cause opportunistic infections adds importance of these findings. PMID- 21977049 TI - Inflammatory cytokines in maternal circulation and placenta of chromosomally abnormal first trimester miscarriages. AB - The impact of abnormal placental karyotype on the inflammatory response within the villous tissue and peripheral circulation of women with miscarriage was evaluated. Villous (n = 38) and venous blood samples (n = 26) were obtained from women with missed miscarriage. Tissue chromosome analysis indicated 23 abnormal and 15 normal karyotypes. Concentration of tumour necrosis factor alpha (TNFalpha), TNF-R1 and TNF-R2, and interleukin (IL)-10 were measured using flowcytometric bead array in fresh villous homogenate, cultured villous extracts, culture medium, maternal whole blood, and plasma. Plasma TNFalpha/IL-10 ratios were significantly (P < 0.05) lower in miscarriages with abnormal karyotype. In the abnormal karyotype group, there were significantly higher levels of TNFalpha (P < 0.01), IL-10 (P < 0.01), TNF-R1 (P < 0.001), and TNF-R2 (P < 0.001) in the villous extracts and culture-conditioned medium compared to normal karyotype group. In miscarriage with abnormal karyotype, there is an exacerbated placental inflammatory response, in contrast to miscarriage of normal karyotype where maternal systemic response is increased. PMID- 21977050 TI - Drosophila as a tool for personalized medicine: a primer. AB - The goal of personalized medicine is to treat each patient with the best drug: optimal therapeutic benefit with minimal side effects. The genomic revolution is rapidly identifying the genetic contribution to the diseased state as well as its contribution to drug efficacy and toxicity. The ability to perform genome-wide studies has led to an overwhelming number of candidate genes and/or their associated variants; however, understanding which are of therapeutic importance is becoming the greatest unmet need in the personalized medicine field. A related issue is the need to improve our methods of identifying and characterizing therapeutic drugs in the context of the complex genomic landscape of the intact body. Drosophila have proven to be a powerful tool for understanding the basic biological mechanisms of human development. This article will review Drosophila as a whole animal tool for gene and drug discovery. We will examine how Drosophila can be used to both sort through the myriad of hits coming from human genome-wide scans and to dramatically improve the early steps in pharmaceutical drug development. PMID- 21977051 TI - Purification and the Secondary Structure of Fucoidanase from Fusarium sp. LD8. AB - The fucoidanase from Fusarium sp. (LD8) was obtained by solid-state fermentation. The fermented solid medium was extracted by citric acid buffer, and the extracts were precipitated by acetone and purified by Sephadex G-100 successively. The results showed that the specific fucoidanase activity of purified enzyme was 22.7 fold than that of the crude enzyme. The recovery of the enzyme was 23.9%. The purified enzyme gave a single band on SDS-PAGE gel, and the molecular weight of fucoidanase was about 64 kDa. The isoelectric point of the enzyme was 4.5. The enzyme properties were also studied. The results showed that the optimum temperature and pH were 60 degrees C and 6.0, respectively; the temperature of half inactivation was 50 degrees C, and the most stable pH for the enzyme was 6.0. K(M), and the V(max) of the enzyme was 8.9 mg.L(-1) and 2.02 mg.min(-1).mL( 1) by using fucoidan from Fucus vesiculosus as substrate. The compositions of the secondary structure of fucoidanase were estimated by FTIR, the second derivative spectra, and the curve-fitting analysis of the amide I bands in their spectra. The results showed that beta-sheet was the dominant component (58.6%) and alpha helix was the least (12%); the content of beta-turn and random coil were 15.39% and 14.5%, respectively. PMID- 21977052 TI - Homology-Driven Proteomics of Dinoflagellates with Unsequenced Genomes Using MALDI-TOF/TOF and Automated De Novo Sequencing. AB - This study developed a multilayered, gel-based, and underivatized strategy for de novo protein sequence analysis of unsequenced dinoflagellates using a MALDI TOF/TOF mass spectrometer with the assistance of DeNovo Explorer software. MASCOT was applied as the first layer screen to identify either known or unknown proteins sharing identical peptides presented in a database. Once the confident identifications were removed after searching against the NCBInr database, the remainder was searched against the dinoflagellate expressed sequence tag database. In the last layer, those borderline and nonconfident hits were further subjected to de novo interpretation using DeNovo Explorer software. The de novo sequences passing a reliability filter were subsequently submitted to nonredundant MS-BLAST search. Using this layer identification method, 216 protein spots representing 158 unique proteins out of 220 selected protein spots from Alexandrium tamarense, a dinoflagellate with unsequenced genome, were confidently or tentatively identified by database searching. These proteins were involved in various intracellular physiological activities. This study is the first effort to develop a completely automated approach to identify proteins from unsequenced dinoflagellate databases and establishes a preliminary protein database for various physiological studies of dinoflagellates in the future. PMID- 21977053 TI - Ethnobiology and Ethnopharmacology of Lepidium meyenii (Maca), a Plant from the Peruvian Highlands. AB - Lepidium meyenii (maca) is a Peruvian plant of the Brassicaceae family cultivated for more than 2000 years, which grows exclusively in the central Andes between 4000 and 4500 m altitude. Maca is used as a food supplement and also for its medicinal properties described traditionally. Since the 90s of the XX century, an increasing interest in products from maca has been observed in many parts of the world. In the last decade, exportation of maca from Peru has increased from 1,415,000 USD in 2001 to USD 6,170,000 USD in 2010. Experimental scientific evidence showed that maca has nutritional, energizer, and fertility-enhancer properties, and it acts on sexual dysfunctions, osteoporosis, benign prostatic hyperplasia, memory and learning, and protects skin against ultraviolet radiation. Clinical trials showed efficacy of maca on sexual dysfunctions as well as increasing sperm count and motility. Maca is a plant with great potential as an adaptogen and appears to be promising as a nutraceutical in the prevention of several diseases. PMID- 21977054 TI - Natural products from ethnodirected studies: revisiting the ethnobiology of the zombie poison. AB - Wade Davis's study of Haitian "zombification" in the 1980s was a landmark in ethnobiological research. His research was an attempt to trace the origins of reports of "undead" Haitians, focusing on the preparation of the zombification poison. Starting with this influential ethnopharmacological research, this study examines advances in the pharmacology of natural products, focusing especially on those of animal-derived products. Ethnopharmacological, pharmacological, and chemical aspects are considered. We also update information on the animal species that reportedly constitute the zombie poison. Several components of the zombie powder are not unique to Haiti and are used as remedies in traditional medicine worldwide. This paper emphasizes the medicinal potential of products from zootherapy. These biological products are promising sources for the development of new drugs. PMID- 21977055 TI - Tai chi for lower urinary tract symptoms and quality of life in elderly patients with benign prostate hypertrophy: a randomized controlled trial. AB - Tai chi exercise has been recommended as suitable for the improvement of health in the elderly. The purpose of this study was to investigate the effects of tai chi on lower urinary tract symptoms (LUTSs), quality of life (QoL), and sex hormone levels in patients with benign prostate hypertrophy (BPH). The elderly patients with BPH were randomized to receive tai chi or usual care. Fifty-six participants were randomized into either the tai chi group (n = 28) or the control group (n = 28). After 12 weeks of treatment, the tai chi group showed significant improvement in LUTS and QoL. There was a significant effect of tai chi on testosterone but no significant effect on insulin or glucose. No serious adverse events were observed during the study period. In conclusion, our results suggest that 12 weeks of tai chi may improve LUTS and QoL in elderly patients with BPH. PMID- 21977056 TI - Efficacy of an Extract of Ocimum tenuiflorum (OciBest) in the Management of General Stress: A Double-Blind, Placebo-Controlled Study. AB - A randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy of OciBest, an extract of Ocimum tenuiflorum Linn. in symptomatic control of general stress. The participants received either placebo (n = 79) or OciBest (n = 71; 1200 mg of actives per day) for six weeks. The severity of stress-related symptoms was self-evaluated by patients at weeks 0, 2, 4 and 6 of the trial period using a symptom rating scale. After six weeks of intervention, scores of symptoms such as forgetfulness, sexual problems of recent origin, frequent feeling of exhaustion, and frequent sleep problems of recent origin decreased significantly (P <= 0.05) in OciBest group as compared with placebo group. Also, the total symptom scores of OciBest group revealed significant reduction (P <= 0.05) as compared to placebo group. The overall improvement in OciBest group was found to be 1.6 times or 39% more in the control of general stress symptoms with respect to placebo. No adverse events were reported during the study. The findings revealed that OciBest was found to be effective and well tolerated by all the patients over the six weeks of study period. PMID- 21977057 TI - DNA vaccine: a promising new approach for chronic hepatitis B therapy. PMID- 21977058 TI - Giant cutaneous melanomas: evidence for primary tumour induced dormancy in metastatic sites? AB - Two patients with giant, 8 cm and 19 cm melanomas of the upper extremity, respectively, are presented and discussed. Both patients had neglected their tumours and sought medical attention only after the appearance of distressing symptoms (for example, bleeding). Palpable lymph nodes were found on physical examination but no evidence of distant metastases was noted on imaging studies despite such enormous primary tumours. Both patients underwent aggressive treatment, including complete surgical resection of the primary tumour and ipsilateral axillary lymph node dissection. One patient had no evidence of local recurrence, but developed metastatic disease at 6 months follow-up. The other patient developed local recurrence and distant metastases within 2 months of resection. PMID- 21977059 TI - Conservative management of complex diverticular disease causing a retroperitoneal perforation. AB - Diverticular disease is very common and may cause symptoms of psoas irritation because of contiguous inflammation arising from the colon affecting the retroperitoneum. Retroperitoneal perforation is rare and is marked by free gas in the adjacent musculature. Rarely infection and associated gas may track into the lower limbs; however, if adequate drainage can be achieved, surgery in the unfit may be avoided. We present a case of a 79-year-old woman with retroperitoneal perforation of diverticular disease presenting with free gas in the leg musculature that was managed conservatively because of associated comorbidities and was associated with the formation of a cutaneous faecal fistula in the lower limb. PMID- 21977060 TI - Acute profound abciximab induced thrombocytopenia: a correct management of a methodological error. AB - Thrombocytopenia is a rare complication of glycoprotein IIb/IIIa treatment. We report a case of an acute profound abciximab induced thrombocytopenia and its successful management. The patient, presenting with unstable angina, underwent percutaneous coronary intervention with implantation of three drug eluting stents without receiving a clopidogrel loading dose according to guidelines. The rapid drop in the platelet count after abciximab elastomeric pump infusion was treated with drug discontinuation and platelet transfusion. The high risk of stent thrombosis was avoided by a timely readministration of the dual antiplatelet treatment. PMID- 21977061 TI - The prevalence of chronic obstructive pulmonary disease in Saudi Arabia: Where do we stand? PMID- 21977062 TI - Sleep from an Islamic perspective. AB - Sleep medicine is a relatively new scientific specialty. Sleep is an important topic in Islamic literature, and the Quran and Hadith discuss types of sleep, the importance of sleep, and good sleep practices. Islam considers sleep as one of the signs of the greatness of Allnuh (God) and encourages followers to explore this important sign. The Quran describes different types of sleep, and these correspond with sleep stages identified by modern science. The Quran discusses the beneficial effects of sleep and emphasizes the importance of maintaining a pattern of light and darkness. A mid-day nap is an important practice for Muslims, and the Prophet Muhammad peace be upon him (pbuh) promoted naps as beneficial. In accordance with the practice and instructions of Muhammad (pbuh), Muslims have certain sleep habits and these sleep habits correspond to some of the sleep hygiene rules identified by modern science. Details during sleep include sleep position, like encouraging sleep on the right side and discouraging sleep in the prone position. Dream interpretation is an established science in the Islamic literature and Islamic scholars have made significant contributions to theories of dream interpretation. We suggest that sleep scientists examine religious literature in general and Islamic literature in particular, to understand the views, behaviors, and practices of ancient people about the sleep and sleep disorders. Such studies may help to answer some unresolved questions in sleep science or lead to new areas of inquiry. PMID- 21977063 TI - Venous thromboembolism-related mortality and morbidity in King Fahd General Hospital, Jeddah, Kingdom of Saudi Arabia. AB - BACKGROUND: Venous thromboembolism (VTE) is a serious and underestimated potentially fatal disease with an effective prophylactic antithrombotic therapy that is usually underused. OBJECTIVES: The primary study objective is to determine the percentage of VTE patients who received prophylactic antithrombotic therapy according to ACCP guidelines. Secondary study objectives are determining prevalence of confirmed VTE mortality among all cause hospital mortalities, measuring adherence to anticoagulation treatment after discharge and number of VTE events among those patients. METHODS: During the period from first of July 2008 till 30 of June 2009, we collected all hospital deaths, all patients with confirmed VTE diagnosis at King Fahd General Hospital, Jeddah, Kingdom of Saudi Arabia. Only patients with confirmed VTE diagnosis were included in the analysis. RESULTS: Five hundred cases with clinical diagnosis of VTE were identified. Out of them 178 were confirmed to be VTE. 36.5% of them received prophylactic antithrombotic therapy. Case fatality rate was 20.8% representing 1.9% of hospital deaths. Case fatality rate was 31% and 3.1% for patients who did not receive thromboprophylaxis and patients who received it, respectively (P < 0.0001). 66.3% and 33.7% of confirmed VTE cases occurred in surgical and medical patients respectively. Only 44.1% of surgical patients and 21.7% of medical patients received prophylaxis (P < 0.01). Case fatality rate is 11% for surgical patients and 40% for medical patients (P < 0.001). Of 141 survived cases, 118 (83.7%) were adherent to anticoagulation therapy after discharge. CONCLUSIONS: VTE prophylaxis guideline is not properly implemented and extremely underutilized. Mortality from VTE is significantly higher in patients who did not receive VTE prophylaxis. In the absence of regular post-mortem practice VTE related mortality rate would be difficult to estimate and likely will be underestimated. Health authorities should enforce VTE prophylaxis guideline within the healthcare system. PMID- 21977064 TI - Post-traumatic pulmonary embolism in the intensive care unit. AB - OBJECTIVE: To determine the predictive factors, clinical manifestations, and the outcome of patients with post-traumatic pulmonary embolism (PE) admitted in the intensive care unit (ICU). METHODS: During a four-year prospective study, a medical committee of six ICU physicians prospectively examined all available data for each trauma patient in order to classify patients according to the level of clinical suspicion of pulmonary thromboembolism. During the study period, all trauma patients admitted to our ICU were classified into two groups. The first group included all patients with confirmed PE; the second group included patients without clinical manifestations of PE. The diagnosis of PE was confirmed either by a high-probability ventilation/perfusion (V/Q) scan or by a spiral computed tomography (CT) scan showing one or more filling defects in the pulmonary artery or its branches. RESULTS: During the study period, 1067 trauma patients were admitted in our ICU. The diagnosis of PE was confirmed in 34 patients (3.2%). The mean delay of development of PE was 11.3 +/- 9.3 days. Eight patients (24%) developed this complication within five days of ICU admission. On the day of PE diagnosis, the clinical examination showed that 13 patients (38.2%) were hypotensive, 23 (67.7%) had systemic inflammatory response syndrome (SIRS), three (8.8%) had clinical manifestations of deep venous thrombosis (DVT), and 32 (94%) had respiratory distress requiring mechanical ventilation. In our study, intravenous unfractionated heparin was used in 32 cases (94%) and low molecular weight heparin was used in two cases (4%). The mean ICU stay was 31.6 +/- 35.7 days and the mean hospital stay was 32.7 +/- 35.3 days. The mortality rate in the ICU was 38.2% and the in-hospital mortality rate was 41%. The multivariate analysis showed that factors associated with poor prognosis in the ICU were the presence of circulatory failure (Shock) (Odds ratio (OR) = 9.96) and thrombocytopenia (OR = 32.5).Moreover, comparison between patients with and without PE showed that the predictive factors of PE were: Age > 40 years, a SAPS II score > 25, hypoxemia with PaO(2)/FiO(2) < 200 mmHg, the presence of spine fracture, and the presence of meningeal hemorrhage. CONCLUSION: Despite the high frequency of DVT in post-traumatic critically ill patients, symptomatic PE remains, although not frequently observed, because systematic screening is not performed. Factors associated with poor prognosis in the ICU are the presence of circulatory failure (shock) and thrombocytopenia. Predictive factors of PE are: Age > 40 years, a SAPS II score > 25, hypoxemia with PaO(2)/FiO(2) < 200, the presence of a spine fracture, and the presence of meningeal hemorrhage. Prevention is highly warranted. PMID- 21977066 TI - Development of Arabic version of Berlin questionnaire to identify obstructive sleep apnea at risk patients. AB - BACKGROUND: Obstructive sleep apnea (OSA) is a common, under-recognized, under diagnosed, under treated, and serious medical condition in adults. Polysomnography (PSG) is the gold standard for diagnosis of OSA; however, prohibitive cost of the test and rarity of sleep laboratory in the Arabic nations limit its access. So, searching for another simple, economical, reliable, and valid tool for identification of OSA at risk patients is of special public concern. OBJECTIVE: This study was conducted to evaluate the reliability and validity of Arabic version of Berlin questionnaire (ABQ) in detection of OSA at risk patients. METHODS: After hospital ethics approval and formal patients consent, 100 patients were subjected to full night PSG study after their response to the developed ABQ. The patients were classified into both low (30) and high risk (70) for OSA using ABQ and validated against apnea hypopnea index (AHI). Reliability was assessed by internal consistency using Cronbach's alpha test and consistency over time using test retest correlation. RESULTS: The study demonstrated a high degree of internal consistency and stability over time for the developed ABQ. The Cronbach's alpha coefficient for the 10-item tool was 0.92. Validation of ABQ against AHI at cutoff >5 revealed a sensitivity of 97%, specificity of 90%, positive and negative predictive values of 96% and 93%, respectively. CONCLUSION: The ABQ is reliable and valid scale in screening patients for the risk of OSA among Arabic-speaking nations, especially in resource-limited settings. PMID- 21977065 TI - What is the optimal blood glucose target in critically ill patients? A nested cohort study. AB - AIMS: There is an uncertainty about what constitutes an optimal level of blood glucose (BG) in critically ill patients. The objective of this study is to identify the optimal BG target for glycemic control in critically ill patients that is associated with survival benefit with the least hypoglycemia risk. SETTING AND DESIGN: This is a nested cohort study within a randomized control trial conducted in a tertiary care center in King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia. METHODS: The study was carried out in a single center to assess the effect of intensive insulin therapy [IIT; target BG 4.4-6.1 mmol/L (80 110 mg/dL)] versus conventional insulin therapy [CIT; target BG 10-11.1 mmol/L (180-200 mg/dL)] in a medical/surgical ICU. All patients were divided into six groups based on the mean daily BG levels. A logistic regression model was used to determine the association of BG and ICU mortality. We compared different outcomes below and above different BG thresholds of 0.1 mmol/L (2 mg/dL) increments using multivariate analyses. STATISTICAL ANALYSIS: Data are presented as mean +/- SD or median with interquartile ranges, unless otherwise indicated. Differences between the six groups were assessed using the chi(2) test. A P-value equal or less than 0.05 was considered to indicate statistical significance. The results were expressed as adjusted odds ratio (aOR) and 95% confidence intervals (CI). Statistical analyses were carried out using the Statistical Analysis Software (SAS, release 8, SAS Institute Inc., Cary, NC, USA). RESULTS: Among six groups, the ICU mortality was least in patients with BG <8.7 mmol/L (<157 mg/dL) compared with patients with BG >=8.7 mmol/L (>=157 mg/dL) [11.5% vs. 21.5%, P = 0.002]. When analyzed using 0.1 mmol increments in average BG, we found that mortality remained unchanged by increasing thresholds of BG up to 8.0 mmol/L (144 mg/dL) and started to rise with thresholds of BG of 8.1 mmol/L (146 mg/dL) and above. The risk of hypoglycemia was the highest with a BG threshold of 6.1 mmol/L (110 mg/dL) and gradually decreased with increasing BG levels to plateau with a BG level of 7.2 mmol/L (130 mg/dL) and higher. CONCLUSION: Our study suggests that a BG level of 8.1 mmol/L (146 mg/dL) and below represents an optimal level in critically ill patients. PMID- 21977067 TI - Evaluation of a transcutaneous carbon dioxide monitor in patients with acute respiratory failure. AB - BACKGROUND: Non-invasive measurement of oxygenation is a routine procedure in clinical practice, but transcutaneous monitoring of PCO(2)(PtCO(2)) is used much less than expected. METHODS: The aim of our study was to analyze the value of a commercially available combined SpO(2)/PtCO(2) monitor (TOSCA-Linde Medical System, Basel, Switzerland) in adult non-invasive ventilated patients with acute respiratory failure. Eighty critically ill adult patients, requiring arterial blood sample gas analyses, underwent SpO(2) and PtCO(2) measurements (10 min after the probe was attached to an earlobe) simultaneously with arterial blood sampling. The level of agreement between PaCO(2) - PtCO(2) and SaO(2) - SpO(2)was assessed by Bland-Altman analyses. RESULTS: Both, SaO(2) from blood gas analysis and SpO(2) from the transcutaneous monitor, and PaCO(2) and PtCO(2) were equally useful. No measurements were outside of the acceptable clinical range of agreement of +/- 7.5 mmHg. CONCLUSIONS: The accuracy of estimation of the TOSCA transcutaneous electrode (compared with the "gold standard" blood sample gas analysis) was generally good. Moreover, TOSCA presents the advantage of the possibility of continuous non-invasive measurement. The level of agreement of the two methods of measurement allows us to state that the TOSCA sensor is useful in routine monitoring of adults admitted to an intermediate respiratory unit and undergoing non-invasive ventilation. PMID- 21977068 TI - Effect of doxycycline in patients of moderate to severe chronic obstructive pulmonary disease with stable symptoms. AB - BACKGROUND: The protease-antiprotease hypothesis proposes that inflammatory cells and oxidative stress in chronic obstructive pulmonary disease (COPD) produce increased levels of proteolytic enzymes (neutrophil elastase, matrix metalloproteinases [MMP]) which contribute to destruction of parenchyma resulting in progressive decline in forced expiratory volume in one second. Doxycycline, a tetracycline analogue, possesses anti-inflammatory properties and inhibits MMP enzymes. OBJECTIVES: To assess the effect of 4 weeks doxycycline in a dose of 100 mg once a day in patients of moderate to severe COPD with stable symptoms. METHODS: In an interventional, randomized, observer-masked, parallel study design, the effect of doxycycline (100 mg once a day for 4 weeks) was assessed in patients of COPD having stable symptoms after a run-in period of 4 weeks. The study participants in reference group did not receive doxycycline. The parameters were pulmonary functions, systemic inflammation marker C-reactive protein (CRP), and medical research council (MRC) dyspnea scale. Use of systemic corticosteroids or antimicrobial agents was not allowed during the study period. RESULTS: A total of 61 patients completed the study (31 patients in doxycycline group and 30 patients in reference group). At 4 weeks, the pulmonary functions significantly improved in doxycycline group and the mean reduction in baseline serum CRP was significantly greater in doxycycline group as compared with reference group. There was no significant improvement in MRC dyspnea scale in both groups at 4 weeks. CONCLUSION: The anti-inflammatory and MMP-inhibiting property of doxycycline might have contributed to the improvement of parameters in this study. PMID- 21977069 TI - The role of mean platelet volume predicting acute exacerbations of cystic fibrosis in children. AB - OBJECTIVE: The aim of this study is to evaluate the relationship between acute exacerbations and the mean platelet volume (MPV) trend in children with cystic fibrosis (CF), to predict the exacerbations. METHODS: A total of 46 children with CF and 37 healthy children were enrolled in the study. White blood cell count (WBC), hemoglobin level, platelet count, mean platelet volume (MPV), and mean corpuscular volume (MCV) were retrospectively recorded. RESULTS: Our study population consisted of 25 (54.3%) males and 21 (45.7%) females with CF and 20 (54.0%) males and 17 (46.0%) females in the healthy control group. The mean age of the CF patients was 6.32 +/- 4.9 years and that of the healthy subjects was 7.02 +/- 3.15 years. In the acute exacerbation period of CF, the MPV values were lower and WBC and platelet counts were higher than those in the healthy controls (P = 0.00, P = 0.00, P = 0.00, respectively). Besides, in acute exacerbation, the MPV values were lower and the WBC count was higher than the values in the non exacerbation period (P 0= 0.01, P = 0.00, respectively). In the non-exacerbation period MPV was lower and platelet count was higher when compared to healthy subjects (P = 0.02, P = 0.04, respectively). CONCLUSION: This study suggests that MPV might be used as a simple, cost effective, diagnostic, predictive indicator for platelet activation in pediatric CF patients related to chronic inflammation, which might be helpful to discriminate or estimate exacerbations. PMID- 21977070 TI - A 38-year-old man with lung cysts. PMID- 21977071 TI - Gluteal abscess: An unusual complication of Bacille Calmette-Guerin. AB - Bacille Calmette-Guerin (BCG) has been used extensively as a vaccine against human tuberculosis. Herein, we describe gluteal tuberculosis abscess due to inadvertently injected BCG a patient with bladder cancer. PMID- 21977072 TI - Pulmonary alveolar microlithiasis with low fluorodeoxyglucose accumulation in PET/computed tomography. AB - Pulmonary alveolar microlithiasis (PAM) is an uncommon lung disease characterized by accumulation of intraalveolar calcifications. The disease can be diagnosed based on the radiological findings. We present a 27-year-old women with five-year history of shortness of breath. She was diagnosed with PAM due to the presence of the characteristic chest X-ray and thorax computed tomography (CT) findings. We performed (18)F-fluorodeoxyglucose (FDG)-PET/CT imaging in order to detect any evidence of inflamation in the lung before deciding an anti-inflammatory treatment. The lung regions with dense calcifications revealed low FDG uptakes (SUVmax: 2.7) and the lung regions without calcifications showed lower FDG uptakes. No further treatment modality was planned besides inhaler salbutamol. Herein, we discuss this rare entity with literature search. PMID- 21977073 TI - Acute respiratory damage in patients with pandemic 2009 AH1N1 influenza: Pulmonary function testing a year after? PMID- 21977074 TI - Effect of patient education on adherence to drug treatment for chronic obstructive pulmonary disease. PMID- 21977075 TI - Insulin resistance, fibrinogen, homocysteine, leptin, and C-reactive protein and metabolic syndrome. PMID- 21977076 TI - Authors' reply. PMID- 21977077 TI - Erratum: ERRATUM. AB - [This corrects the article on p. 5 in vol. 3, PMID: 19561875.]. PMID- 21977078 TI - From the editor. PMID- 21977079 TI - T-cell epitope finding on EPHA2 for further glioma vaccine development: An immunomics study. AB - BACKGROUND: Glioma is a deadly neurological tumor. For modern management of glioma, glioma vaccinotherapy is the new concept. MATERIALS AND METHODS: Based on present biomedical technique, the identification of T-cell epitopes via MHC mapping can help clarify the inter-relationship of tumor and immune system. This process can be performed using advanced immunoinformatics technique. RESULTS: Here, the author performs an immunoinformatics analysis to find alternative epitopes for glioma-related antigen, EPHA2. CONCLUSION: After complete manipulation on EPHA2 molecules, the five best epitopes were derived. PMID- 21977080 TI - Evaluation of functional outcomes in congenital hydrocephalus. AB - AIM: The long term outcomes of congenital hydrocephalus are still not clearly known despite it being a common clinical condition. Several clinical, radiological factors were correlated to predict the functional outcomes. This study aimed to correlate the clinical, radiological parameters with the regional functional outcomes of the brain. MATERIALS AND METHODS: Children with congenital hydrocephalus were divided into Group A with hydrocephalus alone and Group B hydrocephalus with spina bifida. Ventriculoperitoneal shunt surgery was performed by the same surgeon. CT scans and neuropsychological assessments were performed before and serially after the shunt. The clinical and the radiological findings were correlated with the developmental levels during the follow-up. RESULTS: There were 25 children in Group A and 15 children in Group B; 72% in Group A and 93% in Group B were less than 6 months of age at the time of treatment. Forty percent in Group A and 92% in Group B had the signs of hydrocephalus at admission. Cerebrospinal fluid (CSF) diversion results in the reduction in ventricular dilatation and corresponding increase in the cortical mantle thickness. The ventricular size and the cortical mantle thickness were measured serially and correlated with the development in the neuropsychological function. In this study, 80% in Group B reached near normal development in comparison to 33% in Group A. We have noticed a significant correlation in the increase in the regional cortical mantle thickness with corresponding improvement in the functional development. This clearly ratifies the improvement in the frontal and parietal areas having their distinctive effect on the functional development of the child. CONCLUSION: Early CSF diversion and timely intervention seems to benefit functional recovery. It is interesting to note that reconstitution of cortical mantle in different areas of the brain showing corresponding improvement in their respective areas. Large ventricles (head circumference more than 50 cm) recurrent subdural collections and repeated shunt obstructions have a bad influence on the long-term outcome. Unlike the previous belief the children with myelomeningocele can have equal benefit in terms of neuropsychological development after the shunt surgery. PMID- 21977081 TI - Management of attention-deficit hyperactivity disorder. AB - Attention-deficit hyperactivity disorder (ADHD/ADD) is a neurobehavioral disorder of childhood onset characterized by severe, developmentally inappropriate motor hyperactivity, inattention, and impulsiveness that result in impairment in more than one setting. It affects the home, school, and community life of 39% of school-going children worldwide. There is increasing recognition that ADHD symptoms and clinically defined disorder can persist into adult life and are associated with later drug and alcohol misuse and social and work difficulties. Added to that is the extreme variability of the disorder over time, within the same individual, between individuals, and across different circumstances. Treatment with stimulants and nonstimulants has proven effective in different subgroups, with the effectiveness of specific agents most likely related to the primary neurotransmitter involved. However, stimulants with a short duration of action have been problematic for some patients. Parent training and cognitive behavioral therapies represent the most widely adjunct psychosocial interventions to pharmacotherapy. PMID- 21977082 TI - Neuroimaging in epilepsy. AB - Epilepsy is the most common neurological disease worldwide and is second only to stroke in causing neurological morbidity. Neuroimaging plays a very important role in the diagnosis and treatment of patients with epilepsy. This review article highlights the specific role of various imaging modalities in patients with epilepsy, and their practical applications in the management of epileptic patients. PMID- 21977083 TI - Wilson's disease: MRI features. AB - A 15-year-old boy presented with coarse tremors of right hand and dysarthric speech. Neurologic examination demonstrated Kayser-Fleischer rings and dystonic tremor of the right hand. Serum ceruloplasmin and urine copper studies established the diagnosis of Wilson's disease. Brain MRI showed bilateral T2 hyperintensity involving putamen, thalami, and brainstem. Involvement of brainstem revealed the characteristic "double panda sign." PMID- 21977084 TI - Upper extremity constraint-induced movement therapy in infantile hemiplegia. AB - Infantile hemiplegia is one of the clinical forms of cerebral palsy that refers to impaired motor function of one half of the body owing to contralateral brain damage due to prenatal, perinatal and postnatal causes amongst which vascular lesion is the most common causative factor. We report here the effects of constraint-induced movement therapy in a five-year-old female child with infantile hemiplegia on improvement of upper extremity motor skills. PMID- 21977085 TI - Endovascular management of vein of galen aneurysm malformation: A series of two case reports. AB - Vein of Galen Aneurysm malformation is one of the most difficult intracranial vascular lesions to manage. The difficulty in management of its shunts is aggravated by the hemodynamic effect and shunting reflected in the growing brain of infants and children. At present, the therapeutic options are widened by the opening of a new horizon in Intervention Neuroradiology. We present a series of two case reports of these malformations treated using the endovascular method, at our institution. PMID- 21977086 TI - Ewing's sarcoma of the orbit with intracranial extension: A rare cause of unilateral proptosis. AB - Ewing's sarcoma causing unilateral proptosis along with bifrontal extradural infiltration in a child is an unusual presentation. A female patient presented with features of painless proptosis of the left eye with visual deterioration. Her radiology revealed an infiltrating intraorbital, extraconal tumor with intracranial bifrontal extradural extension causing mass effect. Total excision of the intraorbital and intracranial part of the tumor along with postoperative chemo- and radiotherapy brought about a substantial relief. The clinicoradiological presentation and management of this rare entity are discussed. PMID- 21977087 TI - Anterior sacral meningocele presenting as constipation. AB - Anterior sacral meningocele (ASM) is a rare form of spinal dysraphism in children. Usually asymptomatic, it can present as constipation, urinary problems or rarely neurological symptoms. High index of suspicion with careful clinical examination is necessary to make early diagnosis. Magnetic resonance imaging is the investigation of choice. We describe a successfully managed young child with ASM associated with rib and vertebral defects. PMID- 21977088 TI - A report of Joubert syndrome in an infant, with literature review. AB - Joubert syndrome (JS) is a rare autosomal recessive disorder with key finding of cerebellar vermis hypoplasia with a complex brainstem malformation that comprises the molar tooth sign on axial magnetic resonance images. This syndrome is difficult to diagnose clinically because of its variable phenotype. The exact diagnosis is often not made for several years after birth. This report shows that with the availability of magnetic resonance imaging (MRI), especially in developing countries like India, it is quite feasible to make an early diagnosis which may positively affect the subsequent management and outcome. We present a case of JS in a 7-month-old girl who presented to the pediatric outpatient clinic with developmental delay and abnormal eye movements. MRI showed molar tooth configuration of superior cerebellar peduncles, the fourth ventricle shaped like a bat wing and hypoplasia of the vermis which resulted in median approach of the two cerebellar hemispheres. PMID- 21977089 TI - Acute hemorrhagic encephalomyelitis in childhood: Case report and literature review. AB - Acute disseminated encephalomyelitis (ADEM) is an inflammatory immune-mediated disorder which is more common in pediatric patients. The clinical setting is characterized by a rapid onset of encephalopathy and multifocal neurological features. Acute hemorrhagic encephalomyelitis (AHEM) is considered a rare form of ADEM. This report shows a 2-year-old patient who presented with the classical features of ADEM and after 8 weeks developed severe neurological worsening. The second magnetic resonance image (MRI) showed hemorrhagic lesions. Differences in prognosis between ADEM and AHEM justify the investigation of AHEM whenever a patient has neurological recrudescence in a known patient of ADEM. PMID- 21977090 TI - Isolated intramedullary spinal cysticercosis in a 10-year-old female showing dramatic response with albendazole. AB - Neurocysticercosis is the most common parasitic infection of the central nervous system caused by larvae of Taenia solium. Spinal cysticercosis is an uncommon site of cysticercal infection, and isolated intramedullary involvement is even rarer. We present a case of 10-year-old girl who presented with gradual onset paraparesis with sensory loss and bowel and bladder incontinence. Magnetic resonance imaging (MRI) of spine revealed a cystic lesion with mural nodule (scolex) which was diagnostic for cysticercosis. Patient was treated with antihelminthic, which led to marked clinico-radiological improvement. PMID- 21977091 TI - Cervical myelocystocele: Case report and review of literature. AB - Dysraphisms involving cervical region are very rare and there are very few series describing their follow-up in literature. Here, we report a 6-year-old boy who underwent postnatal "cosmetic" repair of posterior cervical cystic lesion and presented to us with a large recurrence with syringohydromyelia and tethering. Tethered cord should be suspected in the presence of meningocele and intact neurology. Treatment protocols of such complicated cervical spinal dysraphisms should include intradural exploration and detethering, with an aim to prevent neurological deterioration in future. PMID- 21977092 TI - An unusual case of 4 level spinal dysraphism: Multiple composite type 1 and type 2 split cord malformation, dorsal myelocystocele and hydrocephalous. AB - The authors here have reported a rare case of a child with a complex spina bifida with two different levels of split cord malformation (SCM) type 1 and single level type 2, a non terminal myelocystocele, coccygeal dermal sinus, bifid fatty filum and hydrocephalus, which substantiates the neuroenteric canal theory and have further tried to highlight the importance of complete Magnetic resonance imaging (MRI) screening of the whole spine and brain with SCM to rule out other associated conditions. The patient was admitted with a leaking myelocystocele with bilateral lower limb weakness. MRI of whole spine with screening of brain was done. Patient underwent 5 operations in the same sitting- (According to classification given by Mahapatra et al.) removal of SCM type 1a at D7-8; removal of SCM type1c at L2-3; removal of SCM type 2 at D10; repair of non terminal myelocystocele at D6-D10; low pressure ventriculoperitoneal shunt on right side with excision of dermal coccygeal sinus; and, excision of bifid fatty filum. The clinicoradiological findings in our patient further substantiate the multiple accessory neuroenteric canal theory in the development of composite type of SCM. The physical and neurological signs of SCM and nonterminal myelocystocele should prompt the neurosurgeon to consider performing the screening MRI of whole spine with brain to rule out other composite types of SCM and hydrocephalus. PMID- 21977093 TI - Diabetes insipidus associated with a thickened pituitary stalk in a case of Langerhans Cell Histiocytosis. AB - Diabetes insipidus (DI) associated with a thickened pituitary stalk is a diagnostic challenge in the pediatric population. Langerhans Cell Histiocytosis (LCH) is a rare cause of this entity. A 4-year-old male child presented with central DI of 1-year duration, associated with a thickened pituitary stalk. The etiology for the same remained elusive as the patient had no other manifestation to suggest LCH. A year later, the patient developed a left frontal scalp swelling. Neuroradiology demonstrated multiple punched out osteolytic lesions in both the frontal bones. The infundibulum was thickened and showed post-contrast enhancement. Histology and immunohistochemistry (IHC) of the biopsy specimen confirmed LCH. The child was administered chemotherapy according to LCH protocol, which resulted in 33% reduction in the size of the skull lesions. The DI was controlled with medical management. The present case highlights the need for serial follow-up and magnetic resonance (MR) imaging that led to a diagnosis of LCH. The clinical presentation and management of central DI and a thickened pituitary stalk is presented and the relevant literature is discussed. PMID- 21977094 TI - Intraoral plexiform neurofibroma involving the maxilla - pathognomonic of neurofibromatosis type I. AB - Neurofibromatosis is one of the phakomatosis (neurodermatoses) which are genetically determined hamartomatous or neoplastic diseases of the skin and nervous system. It is not a single entity, but a group of heterogeneous multisystemic neurocutaneous disorders involving both neuroectodermal and mesenchymal derivatives. Plexiform neurofibroma, a histopathologic variant of neurofibroma, is a hallmark of neurofibromatosis type I (NF-I). It is pathognomonic of NF-I and may be the first sign of neurofibromatosis. It often appears within the first 2 years of life or before adolescence and occurs in only 5% of NF-I cases. We present a case of intraosseous plexiform neurofibroma of the maxilla in a 2-year old female, which is rare, along with the oral manifestations and clinicopathological characteristics. Because NF-I is one of the most common genetic disorders and oral manifestations are common, knowledge of the variability of presentation in children is necessary for prompt diagnosis. PMID- 21977095 TI - Childhood steroid-responsive ophthalmoplegic migraine. AB - Ophthalmoplegic migraine (OM) is characterized by recurrent attacks of headache with paresis of ocular cranial nerves. Previously, it was classified as a variant of migraine, but recently, International Headache Classification (IHCD-II) has reclassified OM to the category of neuralgia. Presently, OM is considered a type of recurrent demyelinating cranial neuropathy. We report an adolescent girl with OM, who had been treated with steroid and showed dramatic improvement. PMID- 21977096 TI - Hemifacial spasm as a manifestation of pilocytic astrocytoma in a pediatric patient. AB - Hemifacial spasm is a disorder of the seventh cranial nerve, which is characterized by irregular, involuntary and recurrent tonic and clonic contractions of the ipsilateral facial expression muscles. This disorder affects mainly adults, and there are few cases reported in childhood. The main etiologies are vascular problems, although tumors are an important cause of hemifacial spasm via a direct or an indirect mass effect. We report a 6-year-old girl who presented with right hemifacial spasm. Magnetic resonance imaging showed a lesion in the cerebellopontine angle, extending from the midbrain to the pons with a slight mass effect on the fourth ventricle. The histological examination revealed a pilocytic astrocytoma. PMID- 21977097 TI - Megalencephalic leukoencephalopathy with subcortical cysts: A report of four cases. AB - Megalencephalic leukoencephalopathy with subcortical cysts is an inherited autosomal recessive disorder with characteristic MRI features and a variable but mild clinical course. Frontal and temporal subcortical cysts are the diagnostic hallmark. It usually presents with pyramidal and cerebellar signs. Megalencephaly is usually detected early. Seizures may be present but are usually easily controlled. It has been reported commonly from a certain ethnicity of northern Indian origin, but its presence is global. We encountered four patients and describe the clinical and radiological features of these patients. Seizures though reported to be uncommon were seen in all our patients. Neuropsychiatric features have not been described as presentation so far but one of our patients had moderately severe depression. All the patients were diagnosed by MRI features and they responded well to symptomatic treatment. PMID- 21977098 TI - Esthesioneuroblastoma presenting with proptosis and bilateral neck metastasis: An unusual presentation. AB - Esthesioneuroblastoma (ENB) presenting simultaneously with proptosis and bilateral neck metastasis is a very rare presentation. ENB is a rare tumor arising from the olfactory epithelium of the nasal vault which frequently invades the cranial base, cranial vault and orbit. ENB has a bimodal age distribution between 11 and 20 years and between 51 and 60 years. ENB accounts for approximately 1 to 5% of intranasal cancers and no consensus has been reached yet regarding the treatment of this tumor. We are reporting a 17-year-old male patient who presented with right eye proptosis with loss of vision and bilateral neck metastasis. Contrast enhanced computed tomography (CECT) and magnetic resonance imaging (MRI) was done which showed Kadish stage C tumor. Nasal biopsy was done to make the diagnosis and the patient was subjected to radiotherapy. Tumor responded to radiotherapy and both the primary lesion and the cervical lymph node metastasis disappeared. The purpose of this study is to report the rare presentation of proptosis along with bilateral cervical lymph node metastasis in this rare sinonasal tumor. PMID- 21977099 TI - Rescue endoscopic third ventriculostomy for repeated shunt blockage. AB - The role of endoscopic third ventriculostomy (ETV) is getting more popular for all types of hydrocephalus. It has several advantages and is also being considered for malfunctioning of ventriculo-peritoneal shunt. A 16-year-old child had fourteen shunt revisions in his life. He was eventually treated with ETV with successful result. Repeated shunt failure can be an additional indication of ETV. PMID- 21977100 TI - Pneumocephalus consequent to staphylococcal pneumonia and meningitis. AB - Pneumocephalus is a rare condition, characterized by the presence of gas in the cranial cavity, resulting from trauma, tumors and surgical or diagnostic procedures. Intracranial infection, without any predisposing factor like trauma or surgical intervention as a cause of pneumocephalus is relatively uncommon. While, intracranial infections by gas producing organisms as a cause of pneumocephalus are well known, a spontaneous intracranial infection caused by Staphylococcus aureus causing pneumocephalus is little known. We report here a child who developed pneumocephalus following staphylococcal lung infection with meningitis and eventually showed complete recovery. Meningitis should be considered as a possible cause of pneumocephalus in absence of trauma and surgical intervention. PMID- 21977101 TI - Split notochord syndrome with neuroenteric fistula. PMID- 21977102 TI - Total migration of a ventriculo-peritoneal shunt catheter into the ventricles. PMID- 21977103 TI - Lamotrigine-induced SIADH in a child with central diabetes insipidus. PMID- 21977104 TI - Supratentorial atypical teratoid rhabdoid tumor: An uncommon childhood tumor. PMID- 21977105 TI - Scalloping characteristics in anterior fontanelle dermoid cyst. PMID- 21977106 TI - Epilepsy, anti-epileptic drugs and bone health in children. PMID- 21977107 TI - Otocephaly: Prenatal and postnatal imaging findings. PMID- 21977108 TI - Brain abscess: Trouble by tip of a top in a child. PMID- 21977109 TI - Pediatric head injury: An epidemiological study. PMID- 21977110 TI - In vivo effects of Faizol Ubat Batuk, a herbal product on aminopyrine metabolism in rat hepatocytes. AB - Traditional medicines, in particular herbal products, have been used abundantly over the years in curing several diseases. Pharmacological interactions of herbal products with modern drugs, however, remain to some extent unknown. Herein, we examined whether co-administration of Faizol Ubat Batuk (FUB), a mixture of aqueous extract of different plants, modifies the metabolism of aminopyrine, a conventional analgesic drug, in rat liver. We used rat hepatocytes outfitted by collagenase perfusion technique. Determination of aminopyrine n-demethylase activity was performed using the Nash colorimetric method, by measuring the amount of formaldehyde produced. Compared to control treatment, FUB significantly increased the hepatic metabolism of aminopyrine in healthy adult male rats. In contrast, the hepatic metabolism of aminopyrine in adult female rats was decreased. Besides, a biphasic effect in n-demethylase activity was observed in young male rats treated with FUB. In a subsequent experiment, FUB did not change the metabolism of aminopyrine in streptozotocin (STZ)-diabetic adult male rats. In conclusion, administration of FUB could affect phase I aminopyrine metabolism in rat heptocytes. In addition, the effects of FUB on hepatic n-demethylase activity were gender and disease dependent. PMID- 21977111 TI - The interrupter technique: feasibility in children in acute asthma. AB - BACKGROUND: Asthma exacerbation's severity is difficult to evaluate, as it is mainly assessed by clinical parameters. Evaluation of lung function during the acute asthma might provide an objective assessment on the severity of respiratory function impairment. OBJECTIVE: To determine feasibility of interrupter technique in evaluating respiratory resistance (Rocc) on children with acute asthmaMethods: The study included 30 children aged 3 to 14 years, diagnosed with asthma, during an exacerbation; severity of acute asthma has been assessed according to the GINA classification 2007, evaluating individual parameters like intercostals retractions, wheezing, air entry intensity, as well as their association in a clinical score. For every patient spirometry, peakflowmetry and the interrupter technique was applied for assessing respiratory function. The feasibility rate for each method was calculated and compared with the clinical parameters. RESULTS: Out of the 30 children examined, the feasibility rate during the attack was 90% for the interrupter technique, 47% for peakflowmetry and only 27% for spirometry. Fifty-three percent of the exacerbations were classified as mild, 30% of moderate intensity and the remaining 37% being classified as severe exacerbations. The baseline Rocc has been correlated with clinical parameters and the clinical severity score. Best correlations were recorded between baseline Rocc and respiratory rate (r=0.73, p<0.0001), Rocc and heart rate (r=0.5, p=0.0076) and Rocc and the clinical score (r= 0.78, p<0.0001). CONCLUSION: The study shows good feasibility of interrupter technique during asthma exacerbations, as well as strong correlation with clinical parameters assessing severity. PMID- 21977112 TI - Pulmonary hypertension during acute respiratory diseases in infants. AB - OBJECTIVES: The study was undertaken to assess whether previously healthy infants with acute respiratory diseases develop elevated pulmonary artery pressures and to identify which type of disease is associated with pulmonary hypertension. MATERIAL AND METHODS: We performed 2D and Doppler echocardiography in 137 infants, aged between 1 and 12 month, from November 2007 to December 2009. 75 infants had acute respiratory diseases (49 bronchiolitis, 16 interstitial pneumonia, 3 bronchopneumonia, 6 episodic wheezing, 1 lobar pneumonia) and 62 were in the control group. We excluded children with congenital heart diseases and other conditions associated with pulmonary hypertension. The method of time to peak velocity corrected for heart rate was used to estimate pulmonary arterial pressure (PAP). We analysed 2 age-subgroups: 1-2 months and 2-12 months. A Student's t-test for independent samples was used to compare the mean values of variables. OUTCOMES: Increased mean pulmonary pressures (>25mmHg) were measured in 18 infants with respiratory diseases, with the next distribution: 14 bronchiolitis, 2 bronchopneumonia, 1 episodic wheezing, 1 interstitial pneumonia. The values were categorized as mild-moderate pulmonary hypertension. Mean PAP were significantly increased in subjects with clinically bronchoobstructive disease (bronchiolitis, episodic wheezing, bronchopneumonia) vs. control (p=0.05 in first age-subgroup and<0.001 in second age-subgroup). In infants with bronchoobstructive disease hospitalization was significantly longer in patients with pulmonary hypertension vs. normal PAP (p= 0.04 in first age-subgroup and 0.005 in second age-subgroup). In patients with bronchoobstructive diseases, mean PAPm and PAPs were significantly increased in subjects with a moderate/severe episode of wheezing at admission vs. a mild episode (p=0.02). Mean PAPm and PAPs were increased in subjects with interstitial pneumonia vs. control, but without statistic significance. CONCLUSION: Echocardiography is a non-invasive investigation, which brings valuable information regarding pulmonary hypertension in infantile acute respiratory pathology. We found increased PAP almost exclusively in bronchoobstructive diseases; the mechanic effect of hyperinflation on pulmonary vessels is probably the dominant mechanism. PHT could be a criterion in establishing the severity of an acute wheezing episode, a prognosis factor and an element of therapeutic guidance. PMID- 21977113 TI - Comparative study using tuberculin from Cantacuzino Institute versus Statens Serum Institute. AB - SETTING: Iasi County, Romania. OBJECTIVE: To evaluate the efficiency of the tuberculin produced by Cantacuzino Institute (ICB) compared to Statens Serum Institute (SSI) tuberculin in a group of high school students. DESIGN: 36 subjects were tested simultaneously with two tuberculin tipes. For each student, the left arm was tested with ICB tuberculin, while the right arm was tested with SSI tuberculin. All tests were single blind, and the subjects did not know which tuberculin type was used for each arm. The tuberculin administration sequence was random. RESULTS: No significant discrepancies were observed in results of both tuberculin reactions. The correlation coefficient was significant (0.95) between both tests (p<0.0001, CI 0.9111-0.9765). Positive results for the tuberculin test were found in 11.1% of the subjects when we used SSI tuberculin. The pain was almost absent at ICB tuberculin injection, comparatively at SSI tuberculin. CONCLUSION: Tuberculin 2u PPD made by Cantacuzino Institute has the same efficiency as tuberculin PPD RT 23 SSI. The findings of present study recommend, in absence of SSI tuberculin, to use Cantacuzino Institute tuberculin for identification of infections with Mycobacterium tuberculosis complex. PMID- 21977114 TI - Association between body composition and bone mineral density in healthy, non obese, young Romanian adults and effects of menopause. AB - INTRODUCTION: The link between bone mass and body composition is widely recognized, but the mechanism remains unclear. Most studies enrolled subjects irrespective of their body weight and only few works were selectively performed on healthy subjects with body mass index (BMI) within normal limits. MATERIAL AND METHODS: We aimed to determine the relevance of body composition parameters to bone mass in healthy, young and non-obese Romanian volunteers (n=42) and in postmenopausal women (n=20) and to establish the effects of menopausal transition. Both bone mineral density (BMD) and body composition were assessed using whole-body dual X-ray absorptiometry (DXA). OUTCOMES: Despite normal mean BMI, large variability of the whole-body fat mass (FM) content was noted, ranging between 18.6-49.7% in women and 22-40.3% in men. Fat mass was not related to bone density; in contrast, BMD at all sites was positively associated to fat-free mass (FFM) in young non-obese women (r=0.34-0.53). In women, the trunk fat mass/leg fat mass ratio was significantly predicted by age (p=0.001), explaining about 20% of the pattern variability. Menopausal status appeared not to significantly influence whole-body fat or FM distribution. A tendency towards a higher trunk FM/legs FM ratio was observed after menopause, but lost after age-adjustment. CONCLUSION: In non-obese subjects, even of young age, the FM content and distribution is highly variable. FFM mass appears to be the main composition contributor to bone mass, at least in young, healthy, non-obese women. Menopause is not associated to major changes of whole-body fat and trunk adipose tissue, although a significant decrease in peripheral FM content and a tendency towards an age-dependent central redistribution of adiposity is noticed. PMID- 21977115 TI - Perioperative management of patients with lung carcinoma and cerebral metastases. AB - OBJECTIVE: The present study proposes to present the importance of perioperative therapeutic management in survival prolongation and the quality of life for patients that have undergone surgery for cerebral metastases secondary to pulmonary tumors. METHOD: During 2001-2009, 40 patients with ages between 43-74 years have been diagnosed in our clinic with pulmonary tumor and cerebral metastases. The patients presented single cerebral lesion (excepting one patient with 2 cerebral metastases) and pulmonary tumor. Intracranial pressure (ICP) was high in all cases. All patients have undergone operation with general anesthesia. RESULTS: For all patients the reduction of ICP and keeping an optimal CPP (cerebral perfusion pressure) was pursued. In 38 cases, general anesthesia was performed with Sevoflurane and opioids (fentanyl, remifentanyl, sufentanyl) and in 2 cases the TIVA (total intravenous anesthesia) technique was used with propofol and remifentanyl. 14 of the patients required intraoperative depletive treatment through administering mannitol 20%. 37 patients (92%) have been discharged with improved neurological condition without showing signs of intracranial hypertension, convulsive seizures and with partially or totally remitted hemiparesis and one patient had worse postoperative neurological status. CONCLUSION: Pulmonary tumor with cerebral metastases represent an important cause for death rate. To solve secondary cerebral lesions, the perioperative management must include assesment and choosing an anesthesia technique with a proper intraoperative management. PMID- 21977116 TI - Arterial hypertension - prevalence of risk factors and morbide associations that increase cardiovascular risk. AB - Hypertension represents a serious problem in Romania, as there are over 3 million hypertensive people in our country. There is a high incidence of deaths caused by hypertension.WE PERFORMED AN ANALYTICAL PROSPECTIVE STUDY THAT AIMS TO DETERMINE: prevalence of arterial hypertension in a population from Cluj county, distribution on age and gender, arterial hypertension severity, association of hypertension with other cardiovascular risk factors. Our study included 2266 patients, age 14 years old up to over 90 years old, both masculine and feminine gender, known with hypertension and new-diagnosed ones. Each subject was submitted to an interview based on a questionnaire. Diagnosis of arterial hypertension was established according to ESH criteria that consider as hypertension: values over 140/90 mmHg. Out of all subjects submitted to the study 647 (29.74%) were diagnosed with arterial hypertension and, from these, 102 (15.13%) were new-diagnosed patients.We found out a predominance of arterial hypertension at the age of 51-60 and over 60, an increased involvement of feminine sex; an association of hypertension with other major cardiovascular risk factors: obesity, diabetes, dislypidemia.Arterial hypertension represents an important health problem in Romania due to an increased prevalence, major impact on morbidity and mortality by cardiovascular and cerebro-vascular disease. These facts accentuate the necessity of an early diagnosis, of making people aware of the severity of the disease and it's impact on their lifestyle. PMID- 21977117 TI - Applicabillity of noninvasive biomarkers in prostate cancer diagnosis. AB - Prostate cancer represents the second leading cause of male cancer-related deaths worldwide. Better indicators of the presence of prostate cancer are needed to avoid unnecessary treatment, predict disease course and develop more effective therapy. Many molecular biomarkers have been described in human serum, urine, seminal fluid and histological specimens that exhibit varying capacities to detect prostate cancer and predict disease course. PMID- 21977118 TI - The benefits of 3D-4D fetal echocardiography. AB - In the last decade 3D and live 3D ultrasound or the so called 4D (3D/4D) in examination of the fetal heart evolved very rapidly with the development of the new technique called Spatiotemporal Image Corelation - STIC, which enables the aquisition of a volume data concomitent with the beating heart. It appears that 3D/4D ultrasound in fetal echocardiography may make an important contribution to the diagnosis of congenital heart disease, to interdisciplinary management, to parental counseling and to medical personal training. PMID- 21977119 TI - Lipoprotein-associated phospholipase A2 as a predictive biomarker of sub-clinical inflammation in cardiovascular diseases. AB - Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a predictor biomarker for incident atherosclerotic disease. Lp-PLA2 has been identified in atherosclerotic plaques, however, its role in atherosclerosis is still under investigation. Lp PLA2 belongs to the superfamily of phospholipase A2 enzymes. It is produced by macrophages that appears to play a role in the atherosclerotic vessel wall. Emerging data seem to suggest that Lp-PLA2 may be proatherogenic, which is an effect thought to be mediated by lypophosphatidylcholine and oxidized nonesterified fatty acids, two mediators generated by Lp-PLA2. Phospholipase A2 plays an essential role in metabolism of membrane phospholipids, it is related to inflammatory reactions, secretion of amyloid precursor protein. Several studies have documented the strong association of Lp-PLA2 with coronary heart disease and stroke in the general population. Lp-PLA2 may be a stronger predictor of recurrent stroke risk. Inflammatory markers have been associated with ischemic stroke risk. Their relationship to prognosis after stroke is unsettled. The present review article focuses particularly on the characteristics of the Lp(a) associated Lp-PLA2 and discusses the possible role of this enzyme in view of the new data. PMID- 21977120 TI - Cohen syndrome - a rare genetic cause of hypotonia in children. AB - Cohen syndrome is a rare, genetic condition, recessively inherited, associated with specific facial dysmorphism, global developmental delay, hypotonia and ophthalmic abnormalities. A delay in making the diagnosis commonly occurs, because of the lack of a definitive molecular test and also because of the clinical variability of the syndrome. In this paper we describe four cases of Cohen syndrome, together with a comparison with other cases reported in the literature, in order to further delineate this condition. PMID- 21977121 TI - The American College of Cardiology Scientific Session - ACC'10, Atlanta, Georgia. PMID- 21977122 TI - Rare Disease Day - at a glance. PMID- 21977123 TI - Dupuytren's contracture: a new perspective on treatment. PMID- 21977124 TI - Comparison of Dopamine and Norepinephrine in the treatment of shock. PMID- 21977125 TI - Is it safe to prolong dual antiplatelet therapy after DES implantation beyond 12 months? PMID- 21977126 TI - More then 12 months of dual antiplatelet therapy after implantation of drug eluting stents? PMID- 21977127 TI - Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of Ticagrelor versus Clopidogrel in patients with stable coronary artery disease. The ONSET/OFFSET study. PMID- 21977128 TI - Dabigatran is as effective as Warfarin in the treatment of acute venous thromboembolism - the RE-COVER study. PMID- 21977129 TI - Obstructive sleep apnea syndrome could be a significant risk factor for the development of type 2 diabetes mellitus. PMID- 21977130 TI - Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. PMID- 21977131 TI - Current epidemiologic trends in Crohn's disease: data from a tertiary referral centre in Bucharest: (Fundeni Institute, Center of Gastroenterology and Hepatology). AB - The purpose of this study was to estimate the incidence and prevalence of Crohn's disease (CD) in South-Muntenia, Bucharest-Ilfov and the Southwest region, using data collected from the main referral center in the area, during 2005 2009.Materials and methods A retrospective, descriptive study was conducted based on the 593 patients with CD admitted to the Center of Gastroenterology and Hepatology, Fundeni Institute, during this period. The incidence and the prevalence were reported per 100,000 inhabitants aged over 18.Results The incidence and the prevalence between 2005-2009 were estimated at 0.49 /100,000 and 1.88 / 100,000 inhabitants respectively. They both described an oscillating trend between 2005-2009, increasing in 2009 by 32% (p = 0.036) and by 69% (p = 0.000) respectively, as compared to 2005. The sex specific incidence rates was slightly, but not significantly, higher among women (0.59) than men (0.49). The average age at admission was 44. A bimodal age distribution was noticed with two peaks: between 30-39 and 50-59 years old. The highest incidence rate was found in the urban areas (1.09) and Bucharest (0.7). The temporal trend analysis showed that incidence of CD does not suffer significant changes over the interval 2010 2014, predicting an annual incidence rate of 0.52 / 100,000.Conclusion Data collected in the main referral center for the South-Muntenia, Bucharest-Ilfov and Southwest regions during the last five years confirms the previously described low frequency of CD in Romania, the bimodal age distribution and later onset of disease. The male to female ratio is close to unity, suggesting that men and women are generally at similar risk. There is a significant increase in both incidence and prevalence of CD when comparing 2005 with 2009. In term of predicting trends, the incidence of CD appears to be relatively stable, whereas the prevalence understandably rises over the interval 2010-2014. A further prospective multicenter study is necessary in order to assess the precise incidence, prevalence CD in Romania and to make more accurate predictions regarding future trends. PMID- 21977132 TI - Metal exposure in the physically and mentally challenged children of Punjab, India. AB - We collected 149 hair samples at the Baba Farid Centre at Faridkot in Punjab, India to evaluate the trace and toxic metal concentration via ICP-MS. A total of 53 elements were tested. The hair of the children tested showed high values for Ba, Cd, Mn, Pb and U, signifying long-term exposure. Urine baseline testing supported hair analysis findings for all the elements listed above; a DMSA (Dimercapto Succinic Acid) challenge test raised urinary values for lead. Testing of six randomly selected water samples showed concentrations above the European maximum contaminant level for uranium (U) in three samples and lead (Pb) in one.Research aim:To evaluate if hair analysis and/or urine provocation confirm or refute long term metal intoxication. To support or refute that hair mineral analysis confirms urine challenge test results. To support or refute that a DMSA urine challenge test provides a valuable treatment option for metal exposure in children. CONCLUSION: Our results documented that hair and urine mineral analysis results are supportive of each other, and are both useful diagnostic tools in chelation therapy. We also documented that a DMSA challenge test confirms long term exposure as detected through hair mineral analysis. This indicates that the chelating agent DMSA (Dimercapto succinic acid) provides a safe and valuable treatment option for lead overexposure. PMID- 21977133 TI - A survey on urinary tract infections associated with the three most common uropathogenic bacteria. AB - OBJECTIVES: The most common uropathogenic Gram negative bacteria are Escherichia coli and Klebsiella pneumoniae. The purpose of this study was to determine the three most frequent bacterial agents causing Urinary Tract Infections (UTI) in patients who referred to Central Laboratory of Dr. Shariati Hospital, during 2 years (January 2006- December 2007). MATERIALS AND METHODS: The registered data were checked and collected by the questionnaires as a retrospective epidemiological survey. Then, the Chi Square tests were performed by SPSS software. OUTCOMES: The results of the present survey revealed that, the first two bacterial agents in different seasons were similar through the surveillance while the third one was variable. The first two frequent bacteria were respectively, Escherichia coli and Klebsiella pneumoniae. CONCLUSION: The gram negative bacteria of Escherichia coli and Klebsiella pneumoniae were the most common uropathogenic bacteria causing UTI. According to the statistical calculations, there was significant association between UTI caused by Escherichia coli and female gender (p<0.05). PMID- 21977134 TI - Maternal and fetal complications of the hypothyroidism-related pregnancy. AB - Thyroid pathology worsens during pregnancy. Hypothyroidism can be pre-existent or may begin during pregnancy period. Most of the patients who presented hypothyroidism during pregnancy have a history of thyroid disease for which they have undergone treatment (medical, surgical or radioisotopes). Hypothyroidism is difficult to be diagnosed during pregnancy as the signs can belong to pregnancy itself. Changes in thyroid function have a major negative impact on both mother and fetus.Complications that arise depend on the severity of hypothyroidism, on how appropriately and early the treatment will be initiated, on other obstetrical and extragenital pathologies associated with the present pregnancy. Clinical symptoms are polymorphic, often nonspecific, and are related mainly to the time of occurrence and to the severity of thyroid hormone deficiency. The appropriate, early administered treatment and maintenance of a normal level of thyroid hormones minimize the risk of maternal and fetal complications and make it possible that the pregnancy may be carried to term without severe complications. PMID- 21977135 TI - The importance of clinical application of molecular biomarkers in bladder cancer detection. AB - It is known that high throughput technologies facilitate the identification of new molecular targets and biomarkers specific for bladder cancer.The new field of molecular medicine promises that clinical outcomes will be improved by directing therapy toward the molecular mechanisms and targets associated with the growth of the patient's tumor.The great challenge remains to improve the measurement of these targets and to translate this wealth of discovery into clinical management of bladder cancer. PMID- 21977136 TI - Rare diseases, from European resolutions and recommendations to actual measures and strategies. PMID- 21977137 TI - Multiple autoimmune syndrome. AB - The co-occurrence of autoimmune diseases has been epidemiologically studied and has aided in our understanding of autoimmunity. The combination of at least three autoimmune diseases in the same patient has defined as multiple autoimmune syndrome (MAS). About 25 percent of patients with autoimmune diseases have a tendency to develop additional autoimmune diseases. MAS is recognized with increasing frequency. Several associations have been proposed as a form of MAS. Multiple autoimmune syndrome can be classified into three groups according to the prevalence of their associations with one another: type 1, type 2 and type 3. Genetic, infectious, immunologic and psychological factors have all been implicated in the development of MAS. In MAS, patients often have at least one dermatological condition, usually vitiligo or alopecia areata. The pathogenesis of multiple autoimmune disorders is not known yet, perhaps environmental triggers and genetic susceptibility are involved. Abnormalities of both humoral and cell mediated immunity have been described. However, as new perspectives develop on the pathogenesis and natural history of autoimmune diseases, a refinement in the methodology for the study of the co-occurrence of disease is warranted in order to maximize the information that one may realize from such studies. This paper presents some recent results of studies in light of current understanding of the natural history of autoimmune diseases. PMID- 21977138 TI - 18q deletion syndrome - A case report. AB - We report on a 3 years old boy with severe mental retardation, hypotonia, deafness, cerebral dysmyelination, low levels of immunoglobulin A and dysmorphic features, bearing a distal deletion of 18q: 18q21-qter. Karyotype analysis by GTG banding was performed, revealing a deletion of the distal fragment of chromosome 18q, ranging from band q21 to qter, later confirmed by Fluorescence In Situ Hybridization (FISH). Whole chromosome painting for chromosome 18 ruled out any cryptic rearrangements involving other chromosomes. An attempted therapy with growth hormone did not bring any improvement and was discontinued due to an unexplained febrile episode and overall regress of the patient. PMID- 21977139 TI - Hydatid cyst of the pancreas causing portal hypertension. AB - Pancreatic localization of hydatid cyst is uncommon. We report a case of a 49 year-old woman who presented with abdominal discomfort, nausea and vomiting. The diagnosis of pancreatic cyst with splenomegaly and portal hypertension was supported on ultrasound, CT-scan and endoscopic ultrasound. Surgical treatment confirmed the hydatid cyst, and included distal pancreatectomy and splenectomy. The recovery was uneventful and the patient remained symptoms free. PMID- 21977140 TI - Polymorphic ventricular tachycardia in acute myocardial infarction treated by thrombolysis: reperfusion, complication or iatrogenic sign? AB - The QT interval prolongation may determine a type of polymorphic ventricular tachycardia named torsades de pointes. This ventricular arrhythmia could also appear after thrombolysis of acute myocardial infarction.Case reports. A 57 years old man was admitted 2 hours after the onset of a posterior-inferior-lateral acute myocardial infarction (reinfarction). He underwent pharmacological revascularization with reteplase. In the first 24 hours after thrombolysis a sustained polymorphic ventricular tachycardia was unregistered after the second dose of a quinolone recommended for a urological problem. Despite of the normal serum potassium and magnesium QTc suffered an augmentation from 400 ms to 480 ms. After beta-blocker augmentation dose and the antibiotic changing, ventricular arrhythmia disappeared without repetition during hospitalization. This ventricular tachycardia was considered precipitated by the quinolones therapy by increasing of QTc interval. It could also be considered a reperfusion sign or a complication of the reinfarction in the same area, which means different therapeutical solutions. PMID- 21977141 TI - Gefitinib improves outcome in patients with advanced non-small cell lung cancer compared with standard chemotherapy. PMID- 21977142 TI - Rheumatoid arthritis vs. diabetes mellitus as risk factors for cardiovascular disease: the CARRE study. PMID- 21977143 TI - Endovascular versus open repair of abdominal aortic aneurysm. PMID- 21977144 TI - Digoxin use increases mortality in end-stage renal disease. PMID- 21977145 TI - Extracoronary arterial calcification in humans is increased after chronic coumarin treatment. PMID- 21977146 TI - Possible new treatment for nonalcoholic steatohepatitis. PMID- 21977147 TI - Dabigatran etexilate shows at least similar effect compared with enoxaparin in prevention of embolic thromboembolism following total hip arthroplasty: (RENOVATE 2 trial). PMID- 21977148 TI - Treatment with Cyclophosphamide for steroid-resistant nephrotic syndrome in children. AB - The management of patients with steroid-resistant nephrotic syndrome remains difficult. We repport our experience with Cyclophosphamide therapy, in an attempt to compare the results between an oral protocol and two i.v. protocols. The complete and sustained general remission rate was 43.1%, which confirms the efficacy of the treatment, especially for children with minimal change nephrotic syndrome. For the i.v. administration we recommend only 6 month of therapy, due to severe side-effects in longer courses. PMID- 21977149 TI - Frequency of the Methylenetetrahydrofolate REDUCTASE 677CT and 1298AC mutations in an Iranian Turkish female population. AB - INTRODUCTION: Gene-environmental interactions in the pathway of folate metabolism influence greatly the embryonic development. Individual specific MTHFR 677C/T and 1298A/C mutations are known as risk factors for predisposition to human disorders. Therefore, we studied the frequencies of the MTHFR 677CT and 1298AC mutations in a female general population from Iranian Azeri Turkish. MATERIAL AND METHODS: We studied 108 unrelated women from Iranian Azeri Turkish general population. Genomic DNA was extracted using standard procedure. The MTHFR 677CT and 1298AC mutations determined by PCR-RFLP method. OUTCOMES: The frequencies (percent) at position 677 for C and T alleles were 159(74%), 57(26%), and for CC, CT, and TT genotypes were 59(54.6%), 41(38%), and 8(7.41%) respectively. The frequencies (percent) at position 1298 for A and C alleles were 136(63%), 80(37%), and for AA, AC, and CC genotypes were 43(39.8%), 50(46.3%), and 15(13.9%) respectively. CONCLUSIONS: The frequency of MTHFR 677 C and T alleles were 0.74 and 0.26 while that of MTHFR 1298 A and C alleles were 0.63 and 0.37 in present study, respectively. This is the first report in its own kind in Iranian Azeri Turkish women. PMID- 21977150 TI - Clinical relevance of cytogenetics to pediatric practice. Postnatal findings of Patau syndrome - Review of 5 cases. AB - INTRODUCTION: Patau syndrome (trisomy 13) is one of the most common chromosomal anomalies clinically characterized by the presence of numerous malformations with a limited survival rate for most cases. Babies are usually identified at birth and the diagnosis is confirmed with genetic testing. MATERIALS AND METHODS: In this review we outline the clinical and cytogenetic aspects of trisomy 13 and associated phenotypes for 5 cases analyzed in the last 3 years, referred to our Clinical Genetics Department. For each child cytogenetic analysis was performed to determine the genetic variant; also, the patients were investigated for other associated malformations (cardiac, cerebral, renal, ocular anomalies). DISCUSSION: All 5 cases presented multiple malformations, including some but not all signs of the classical clinical triad suggestive of Patau syndrome. The cytogenetic investigation confirmed for each case the suspected diagnosis and also indicated the specific genetic variant, this being a valuable information for the genetic counselling of the families. CONCLUSION: The application of genetic analysis can increase diagnosis and prognosis accuracy and have an impact on clinical management. PMID- 21977151 TI - Serum uric acid and cardiovascular disease. PMID- 21977152 TI - Interventricular septal or standard apical pacing in pacing dependent patients: still a dilemma? PMID- 21977153 TI - Reactions of the immune system in epilepsy. AB - Epilepsy may present as a symptom of many neurological disorders and often an etiological explanation cannot be identified. There is growing evidence that autoimmune mechanisms might have a role in some patients. The evidence for immunological mechanisms in epilepsy can be examined within the following three main areas: the childhood epilepsy syndromes, epilepsy associated with other immunologically mediated diseases, and the more common unselected groups of patients with epilepsy. Autoimmunity was recently suspected to be involved in the pathology of certain human epilepsies. This includes numerous reports of the detection of theoretically relevant serum autoantibodies, experimental data showing that antibodies can be epileptogenic, and a response of some epilepsy syndromes to immunomodulation. The high prevalence of epilepsies in specific immune diseases suggests that immune system may play a role in the pathogenesis of epilepsy or might be associated with it. There is some evidence that immune mechanisms play a role in the pathogenesis of some epilepsy syndromes. PMID- 21977154 TI - Evidence-based pathophysiology of glaucoma. PMID- 21977156 TI - Eating chocolate twice a week reduces heart failure incidence. PMID- 21977155 TI - Cardiopulmonary exercise testing in differential diagnosis of dyspnea. PMID- 21977157 TI - Routine screening by prostate specific antigen for prostate cancer seems unreasonable. PMID- 21977158 TI - Anemia and iron deficiency - New therapeutic targets in heart failure? PMID- 21977159 TI - Susceptibility to exacerbation in chronic obstructive pulmonary disease - Data from the ECLIPSE study. PMID- 21977160 TI - An entirely subcutaneous implantable cardioverter-defibrillator. PMID- 21977161 TI - Is homoarginine level associated with high cardiovascular risk and mortality? PMID- 21977162 TI - Vitamin D deficiency is associated with sudden cardiac death, combined cardiovascular events, and mortality in haemodialysis patients. PMID- 21977163 TI - Sibutramine should be excluded from use in obese patients with preexisting cardiovascular disease. PMID- 21977164 TI - The ESC Scientific Session 2010, Stockholm, Sweden. PMID- 21977165 TI - B-Type Natriuretic Peptide (BNP) and Left Ventricular (LV) Function in Patients with ST-Segment Elevation Myocardial Infarction (STEMI). AB - BACKGROUND: After acute myocardial infarction (AMI), left ventricular (LV) function is a well-established prognostic marker. Recent studies indicate that serum levels of brain natriuretic peptide (BNP) also represent an prognostic marker in this setting but so far without a precise cut-off value. OBJECTIVE: The aim of this study was to assess the predictive value of BNP serum levels for LV function assessed by echocardiography in STEMI patients undergoing revascularization. METHODS: We prospectively studied a cohort of 88 consecutive patients (mean age 51.6 years, 88.6% males) hospitalized in our clinic for STEMI in Killip class I (50% anterior infarction), who underwent reperfusion therapy. Serum BNP levels were measured on admission, at 24h and at 30 days after reperfusion. Detailed echocardiography was performed at baseline, at 24 hours after reperfusion, on discharge and at follow-up at 1 month. Left ventricular systolic and diastolic dysfunction were defined by LVEF < 45% and E/A ratio respectively. RESULTS: ROC curve analysis showed that BNP measurements on admission and at 24 hours after revascularization have no predictive value neighter for diastolic LV dysfunction in anteior or inferior AMI patients, nor for systolic LV dysfunction in inferior AMI patients. Only BNP levels at 24 hours after revascularization can predict systolic LV dysfunction in anterior AMI patients with a 90.3% sensitivity and a 60% false positive rate at a cutt off value of 90pg/ml. CONCLUSIONS: Early measurement of BNP levels may allow early prediction of anterior STEMI patients at risk of developing systolic LV dysfunction after revascularization therapy. PMID- 21977166 TI - The bronchoalveolar lavage pattern in radiation pneumonitis secondary to radiotherapy for breast cancer. AB - BACKGROUND AND PURPOSE: Radiotherapy in breast cancer patients is limited by lung tissue tolerance. Two complications involving the lung are known: radiation pneumonitis (RP) and radiation fibrosis. The aim of the study was to evaluate the pattern of bronchoalveolar lavage (BAL) in patients with RP after radiotherapy for breast cancer in symptomatic and asymptomatic patients. MATERIAL AND METHODS: Sixty-five female patients (mean age 58.3 yrs) with RP after radiotherapy for breast cancer were included in the study. The majority of patients had previous breast surgery (mastectomy or lumpectomy and axillary dissection) and received doses of radiations of 45-50Gy. All patients had adjuvant chemotherapy with cyclophosphamide, 5-fluorouracil, and epirubicin or methotrexate. RESULTS: All patients had an infiltrate or consolidation on chest radiography confined to the upper lobe of the irradiated lung, as marker of RP. Based on the presence or absence of symptoms, we divided the patients in 2 groups: 49 patients (75.4%) with symptomatic RP (fever, cough, dyspnea, chest pain and fatigue) and 16 patients (24.6%) without any symptom. Symptomatic RP patients had a BAL with significant increase in total cells (18.0+/-12.2 x10(6) cells*100mL-1) when compared to BAL in asymptomatic patients (11.9+/-6.2 x10(6) cells*100mL-1), p=0.01. Lymphocytosis in BAL was significantly increased in symptomatic group, compared with asymptomatic one (35.4+/-18.7% vs. 26.1+/-14.3%, p=0.045), with predominance of T lymphocytes (CD3). It was also a predominance of CD4 lymphocytes in all patients, but the CD4/CD8 ratio was inside normal range in the majority of cases. Five patients had clinical features of bronchiolitis obliterans organizing pneumonia (BOOP) secondary to irradiation with increased percentages of lymphocytes, neutrophils, eosinophils, and mast cells in BAL and one patient without history of atopic disease had a percentage of 40% eosinophils. Only a mild reduction in diffusing capacity for carbon monoxide was seen in both groups on pulmonary function tests. The lung volumes were normal in all patients. CONCLUSIONS: Lymphocytic alveolitis was the marker of radiation pneumonitis in all patients. The degree of the inflammatory reaction of the lungs was correlated with the presence of symptoms. The lymphocytic alveolitis consisted mainly of T lymphocytes, with a predominance of CD4 subset in both groups, but the CD4/CD8 ratio remained mostly into normal range. PMID- 21977167 TI - Mortality Risk and Etiologic Spectrum of Community-acquired Pneumonia in Hospitalized Adult Patients. AB - BACKGROUND: The etiology of community-acquired pneumonia (CAP) is specific to each region, as proved by numerous studies conducted so far. Knowledge of these data is essential in developing guidelines for antibiotic prescription. Assessment of severity of CAP patients is crucial in determining the risk of mortality and the site of care. Unusual bacterial etiologies may increase the risk of mortality. OBJECTIVE: First outcome was the identification of pathogens in CAP patients requiring hospitalization and secondary to determine factors that correlate with increased risk of mortality. MATERIAL AND METHODS: A prospective study of patients over 18 years of age hospitalized with CAP from whom pathological products were taken (mainly sputum) for bacteriological analysis (microscopy and culture). RESULTS: 120 patients were evaluated over a period of three years (2008-2010); we could identify a bacterial etiology in 33 cases (27.5%). The most commonly isolated were S. pneumoniae (11 cases), H. influenzae (9 cases) and Gram-negative enteric bacilli (12 cases). The mortality rate was 9.2%, significantly higher in the age group over 65 years and in patients with hypoxemia, impaired consciousness and high CURB 65 score, but the only independent factor for the mortality risk prediction was the presence of confusion on admission. CONCLUSIONS: S. pneumoniae, H. infuenzae and enteric Gram negative bacilli remain the most frequent cause of CAP in hospitalized patients in Romania and the first line of antibiotic treatment should be targeted. The only independent risk factor for mortality risk was the presence of disorders of consciousness on admission. PMID- 21977168 TI - Cirrhosis and Chronic Viral Hepatitis as Risk Factors for Hepatocellular Carcinoma: Romanian Single-clinic Experience. AB - INTRODUCTION: Hepatocellular carcinoma (HCC) represents the fifth most common cancer worldwide, while being the third leading cause of death by cancer. The primary risk factor for HCC seems to be liver cirrhosis. A large majority of these patients have a history of viral hepatitis. MATERIALS AND METHODS: We selected a study lot consisting of 244 patients diagnosed with HCC, admitted between 2006 and October 2009 in the Emergency County Hospital of Craiova, Romania along with an age and gender matched control group, consisting of patients with no history of HCC or other malignancies. We interviewed all subjects regarding their alcohol consumption and background environment. All subjects underwent hepatitis B surface antigen (Hbs Ag) and anti-HCV antibodies (Anti-HCV Atb) serological determinations. RESULTS: The study group consisted of 148 males and 96 females. Liver cirrhosis (LC) was present in 84% of the study lot, 10% associated viral B hepatitis (HBV) and 6% viral C hepatitis (HCV), with no signs of LC. We found LC to be an important risk factor for HCC (RR 6.53, CI 95% 3.18-13.38). The RR and 95% CI of HCC were 4.51 (2.48-8.21) for HbsAg positivity. We noticed a strong correlation (Chi-square test, p<0.001) between the rural environment and the association with LC. HVB was also more present in patients coming from rural areas (p< 0.01). Alcohol intake was present in 89% of the whole lot, being more correlated with the presence of LC as well as with HbsAg positivity (RR 9.165, CI 95% 4.43-18.92). CONCLUSION: Cirrhosis proved to be the primary risk factors for HCC. We underline the fact that HCC was found to be directly associated with viral hepatitis, without evident LC. Further studies are needed in order to establish if intensified HCC screening, especially in rural areas, is required in patients with newly diagnosed viral hepatitis. The increased prevalence of HBV infections might encourage HBV vaccinations as an efficient tool to prevent HCC. PMID- 21977169 TI - Prospective Comparison of Two Brands of Tuberculin Skin Tests and Quantiferon-TB Gold in-tube Assay Performances for Tuberculosis Infection in Hospitalized Children. AB - OBJECTIVE: The study compared two brands of tuberculin skin tests (TST): PPD RT 23, (SSI, Denmark) and PPD IC 65, (Cantacuzino Institute, Romania), 2 TU/ 0.1 ml each, with an interferon gamma release assay [IGRA], Quantiferon-TB Gold (QFT). MATERIAL AND METHODS: QFT was performed on whole blood samples, before TSTs, on 60 children with tuberculosis (TB), BCG vaccinated, admitted in a paediatric pneumophtisiology hospital. The proportion of boys (51.6 %) and girls (48.3 %) was nearly equal, the mean age of subjects was 9.44 years (SD= 5.37 years; variance= 28.83). RESULTS: With TST induration >= 10 mm considered as positive response, only 47.46 % of children classified positive with RT23 and 48.27 % with IC-65, were IFN-gamma positive.We obtained a very good agreement between the two tuberculins (59/60 for RT 23 and 58/60 for IC 65), while for QFT, which confirmed as positives only 27/60, i.e. 45 % (18/60 were indetermined, 15/60 were negatives). CONCLUSIONS: The tests did not agree on positive results, showing a low redundancy between in vitro and in vivo measurements, suggesting that independent aspects of anti-mycobacterial immunity are being measured by these tests.The specificities of the assays could not been calculated since all the children had TB, confirmed by bacteriological and/ or clinical and radiological data. Further comparison of TST and QFT, may determine whether such discordance reflect a higher specificity of QFT. Meantime, we are trying to obtain a recombinant PPD, using a cocktail of specific M. tuberculosis (M.tb) antigens, in order to eliminate any interference with BCG in skin test reactions. PMID- 21977170 TI - Urinary Tract Infections Associated with Candida albicans. AB - OBJECTIVES: Candida albicans is an opportunistic fungal pathogen which causes urinary tract candidiasis in humans. In this research, we tried to find out the frequency of the Urinary Tract Infections associated with Candida albicans in patients who referred to Central Laboratory of Dr. Shariati Hospital, during 2 years (April 2006- April 2008). MATERIALS AND METHODS: According to the archived recorded data, the questionnaires were filled out. At the end of this retrospective research, the statistical tests of Chi Square were operated through SPSS software version 15. OUTCOMES: The results showed that, the Urinary Tract Infections associated with Candida albicans included 6.8% of patients. The remaining 93.2% of Urinary Tract Infections had related to bacterial pathogens. CONCLUSIONS: The statistical analyses confirmed the significant association between Urinary Tract Infections caused by Candida albicans and female gender (P<0.05). PMID- 21977171 TI - RFC - 1 Gene Polymorphism and the Risk of Down Syndrome in Romanian Population. AB - BACKGROUND AND AIMS: There is evidence that the polymorphisms of the genes involved in folate metabolism may be associated with higher risk of Down syndrome (DS) pregnancy. The aim of the present study was to investigate the effect of A80G polymorphism in reduced folate carrier 1 (RFC1) gene on the maternal risk for DS. METHODS: In our study, twenty-two DS mothers and forty-two mothers who had no children with DS were evaluated. Genomic DNA was isolated from whole peripheral blood collected on EDTA, using peqGOLD blood DNA mini kit (ATP Biotech) following the manufacturer's instructions. RESULTS: The results show that the frequencies of RFC1 alleles, as well as the frequencies of RFC1 A80G genotypes (GG, GA, AA, GA+AA) do not correlate with DS pregnancies, demonstrating no difference between the case and control groups. CONCLUSIONS: In the present study, we did not find any statistically significant association between RFC-1 polymorphic genotype and history of DS pregnancies; thus, the relationship between RFC-1 polymorphism and DS appears to be only a supposition and the next step in our study is the catamnestic evaluation of our patients with DS babies for two years. PMID- 21977172 TI - Extra-articular Manifestations in Rheumatoid Arthritis. AB - Rheumatoid arthritis (RA) is a systemic autoimmune disease whose main characteristic is persistent joint inflammation that results in joint damage and loss of function.Although RA is more common in females, extra-articular manifestations of the disease are more common in males. The extra-articular manifestations of RA can occur at any age after onset. It is characterised by destructive polyarthritis and extra-articular organ involvement, including the skin, eye, heart, lung, renal, nervous and gastrointestinal systems. The frequence of extra-articular manifestations in RA differs from one country to another. Extra-articular organ involvement in RA is more frequently seen in patients with severe, active disease and is associated with increased mortality. Incidence and frequence figures for extra-articular RA vary according to study design. Extra-articular involvement is more likely in those who have RF and/or are HLA-DR4 positive. Occasionally, there are also systemic manifestations such as vasculitis, visceral nodules, Sjogren's syndrome, or pulmonary fibrosis present. Nodules are the most common extra-articular feature, and are present in up to 30%; many of the other classic features occur in 1% or less in normal clinic settings. Sjogren's syndrome, anaemia of chronic disease and pulmonary manifestations are relatively common - in 6-10%, are frequently present in early disease and are all related to worse outcomes measures of rheumatoid disease in particular functional impairment and mortality. The occurrence of these systemic manifestations is a major predictor of mortality in patients with RA.This paper focuses on extra-articular manifestations, defined as diseases and symptoms not directly related to the locomotor system. PMID- 21977174 TI - For Patients with Acute Promyelocytic Leukemia the Arsenic Trioxide Improves Event-free and Overall Survival. PMID- 21977175 TI - Teriparatide and bone regeneration in the jaw. PMID- 21977173 TI - Systemic inflammation and early atheroma formation: are they related? AB - Atherosclerosis is a chronic inflammatory disease started by endothelial injury and defined by arterial wall load with free and esterified cholesterol, followed by subintimal focal recruitment of circulating monocytes and T-lymphocytes that heals by fibrosis and calcification. Inflammation plays a crucial role in atherogenesis either by local cellular mechanisms or humoral consequences easily measurable in plasma. In most cases inflammation and endothelial dysfunction are triggered by cardiovascular risk factors: hypercholesterolemia, hypertension, smoking or diabetes. In other cases inflammation precedes atherosclerotic changes that occur in autoimmune diseases, as systemic lupus erythematosus and rheumatoid arthritis. In these diseases atherogenesis is mostly independent from conventional risk factors. Irrespective of its cause systemic inflammation is correlated with cardiovascular events, but currently there are controversial results regarding inflammatory markers and early atherosclerotic process. We designed a study to identify if the amplitude of inflammation expressed by multiple serum markers is correlated with the severity of the atherosclerotic process measured by coronary atheroma volume and carotid intima-media thickness. The selected inflammatory markers are associated with different pathogenic steps in atherogenesis: acute phase reactants (C-reactive protein); pro-inflammatory cytokines (TNF-alpha, interleukin-6 and -18); endothelium activation markers (soluble VCAM-1, ICAM-1); and specific factors (anticardiolipinic antibodies). We aim to enrol the two different patient subsets with early atherosclerosis: one with conventional risk factors and one with autoimmune diseases without traditional risk factors, in whom inflammation is part of the systemic disease progression. PMID- 21977176 TI - The Safety and Efficiency of Proton Pump Inhibitors during Pregnancy and Conception. PMID- 21977177 TI - Self-testing of International Normalized Ratio. PMID- 21977178 TI - Sex-related Differences of Chronic Obstructive Pulmonary Disease Impact on Life Quality: the Platino Study. PMID- 21977179 TI - Antioxidants rich foods may influence chronic obstructive pulmonary disease evolution. PMID- 21977180 TI - Epidemiology of hypertensive kidney disease: diagnosis. PMID- 21977182 TI - Effect of daily aspirin on long-term risk of death due to cancer. PMID- 21977181 TI - Peritoneal transport testing. PMID- 21977183 TI - A Multiplex Allele Specific Polymerase Chain Reaction (MAS-PCR) for the Detection of Factor V Leiden and Prothrombin G20210A. AB - INTRODUCTION: In order to determine the frequencies of factor V Leiden and prothrombin G20210A point mutations in the Iranian population with Azeri Turkish origin. MATERIAL AND METHODS: 120 unrelated individuals from general population randomly selected and were examined for factor V Leiden and prothrombin G20210A mutations using a multiplex allele specific polymerase chain reaction (MAS-PCR) assayOutcomes: The frequency of prothrombin G20210A mutation was 2.08%, which means 5 chromosomes out of 240 chromosomes had prothrombin G20210A mutation. The distribution of prothrombin 20210 GG, GA, AA genotypes and prothrombin 20210A allele were 37(92.5%), 3(7.5%), 0(0%) and 3(3.75%) in males and 78(97.5%), 2(2.5%), 0(0%) and 2(1.25%) in females, respectively. Factor V Leiden was not found in our tested group (zero chromosomes out of 240 chromosomes). Analysis of the observed frequencies in the studied groups indicates that there is no statistically significant difference between females and males, regarding prothrombin G20210A mutation (p value>0.05). CONCLUSIONS: This is the first study in its own kind in this population and implies that the frequency of Factor V Leiden G1691A (R506Q, FV-Leiden) allele is extremely low but the prothrombin G20210A mutation is more frequent in the tested group. PMID- 21977185 TI - Adolescent idiopathic scoliosis and osteopenia). AB - INTRODUCTION: Generalized low bone mass and osteopenia in both axial and peripheral skeleton in adolescent idiopathic scoliosis (AIS) have been reported in literature. However, the exact mechanisms and causes of the bone loss in AIS are not identified yet. OBJECTIVE: Therefore, this study examined the relationship between AIS and bone loss represented by: serum concentration of soluble receptor activator of nuclear factor-kB ligand (RANKL), serum level of osteoprotegerin (OPG), serum level of osteocalcin (OST), parathormon (PTH) and BMI. MATERIALS AND METHODS: We analyzed 15 patients with AIS and compared to the group of 8, age and gender-matched healthy controls. The bone markers in patients with AIS were disturbed compared with than in control individuals. Statistical analysis was performed by using t-test for independent samples. RESULTS: The mean RANKL and RANKL to OPG ratio in patients with AIS were increased compared with that in control subjects. The RANKL and RANKL to OPG ratios were negatively correlated to serum OPG levels in both groups. These findings mean that the imbalance and the disturbed interaction of RANKL and OPG may be an important cause and pathogenesis in osteopenia in AIS. CONCLUSION: Research date showed an important correlation between osteopenia and AIS. The level significant higher of osteocalcin (p<0.01) and RANKL (p<0.01) was observed at adolescents with idiopathic scoliosis comparing with control group. OPG show no differences between the groups of study. RANKL/OPG ratio was significant higher compared with control group. Higher levels of RANKL, in the presence of increased levels of osteocalcin, may induce modification in bone remodelling due to imbalance in RANKL/OPG system. PMID- 21977184 TI - Epidemiological survey 6 years apart: increased prevalence of asthma and other allergic diseases in schoolchildren aged 13-14 years in cluj-napoca, romania (based on isaac questionnaire). AB - BACKGROUND: The prevalence of asthma and allergy has increased during recent decades. OBJECTIVE: We investigate the prevalence of asthma and other allergic diseases in children aged 13-14 years and we evaluate the trend of prevalence after an interval of 6 years. MATERIAL AND METHODS: We used a core questionnaire designed by the International Study of Asthma and Allergy in Children. In 1991, the questionnaire was administered to 2,866 children from a Romanian city and during 2001 to 1,657 children from the same area. RESULTS: The prevalence of asthma increased from 3.3% in 1995 to 5.5% in 2001 (p<0.001). In 1995, 4.3% of children reported asthma-related symptoms, significantly fewer than the percentage 6 years later (13.6%; p<0.00001). Similar results were obtained with regard to allergic rhinitis (13.6% versus 20%; p<0.00001) and eczema (11.5% versus 16.2%; p=0.00015). As far as gender differences are concerned, in the first stage of study all three allergic disorders were found to occur more frequently in females. In the study undertaken in 2001, females proved to have a higher prevalence of asthma (p=0.226), but a lower prevalence for allergic rhinitis (p=0.121) and eczema (p=0.064). CONCLUSIONS: The prevalence of asthma and allergy increased significantly during the past 6 years. PMID- 21977186 TI - Total knee arthroplasty following high tibial osteotomy - a radiological evaluation. AB - The purpose of this study was to evaluate the results of total knee arthroplasty (TKA) following a closed wedge high tibial osteotomy (HTO). A total of 16 TKAs were performed in 16 pacients who had previously undergone a closed wedge (HTO) as a treatement for knee osteoarthritis. The radiographic results were evaluated with respect to the femurotibial angle (FTA), joint line height (JLH), tibial bone resection and Insall-Salvati ratio. The FTA improved in average, from 6.5 degree of varus preoperatively at 5.7 degree of valgus postoperatively. The JLH averaged 14.34 mm preop and 13.81 mm at the last follow-up. The amount of tibial bone resection averaged 5.98 mm, face to 7.5 mm for knees without HTO. The Insall Salvati ratio was 1.127 preop and 1.172 postop. A meticulous surgical technique may lead to satisfactory results in TKA after HTO, considering the correction of the deformity, the re-estabilish of JLH and the amount of the tibial bone resection. PMID- 21977187 TI - An in vitro Survey on the Apoptotic Effects of UVB Ray in Bacillus anthracis. AB - OBJECTIVES: Bacillus anthracis as the bacterial agent of anthrax, is spread in different geographical zones around the world.The purpose of this survey was to observe eventual apoptotic reactions in total genomic DNA of UVB irradiated colonies of Bacillus anthracis. MATERIALS AND METHODS: The colonies of Bacillus anthracis were exposed to UVB ray for 10 minutes; then, the DNA molecules of control and irradiated colonies were extracted. Finally, the DNA samples mixed in loading dye, were run in 1% agarose gel containing fluorescent dye of ethidium bromide to produce visible DNA bands. OUTCOMES: Neither smear nor DNA laddering band were detected upon the agarose gel. CONCLUSIONS: According to the present protocol, the UVB ray can not induce apoptosis feature in colonies of Bacillus anthracis. It seems that the recovery and protection systems in Bacillus anthracis can resist against eventual UVB disorders. PMID- 21977188 TI - Difficulties in Celiac Disease Diagnosis in Children - A case report. AB - Diagnosis of celiac disease in a patient with lactose intolerance has special importance having implications for the treatment of both diseases. The authors present the case of a 2 years old girl, first diagnosed with enterocolitis, but her clinical evolution revealed a complex situation: both celiac disease and secondary lactose intolerance. We present the case as a special situation in clinical pediatric practice that must be taken into account more often. PMID- 21977189 TI - Rehabilitation in a patient with replantation of amputated distal leg. AB - BACKGROUND: Many studies have been reported on replantation of an upper extremity after traumatic amputation, but there are only a few case reports on replantation of the lower extremities rather than amputation surgery. This is due to preoperative factors, complications and the possibility of good prosthetic substitution.We describe here the dynamic evaluation necessary for a continuous rehabilitation treatment in a subject with replanted left foot after traumatic amputation. CASE REPORT: A 58-year-old male person with amputation of the left leg at the level of the left talocrural joint, with talar dome and bimalleolar fractures and complete section of the blood vessels, nerves and tendons was considered for replantation surgery 7 hours after a traumatic injury.For an accurate evaluation of the postoperative conditions over time, clinical functional assessment combined with imaging and neurophysiological examination were conducted.Rehabilitation program is aimed to train the motor and sensory function of the replanted foot and to prevent undesired biomechanical changes that limit person's ability to perform everyday tasks. During the rehabilitation program there were a progressive recovery of the patient's protective sensation, active motion angles of the left ankle joint and muscle power of the replanted leg. Those are sufficient for walking activity and help the patient considerably in performing his everyday minimal housework. CONCLUSIONS: A well designed postoperative dynamic rehabilitation program is necessary in order to regain functionality after successful distal leg replantation surgery. The clinical and imaging evaluation support a dynamic rehabilitation program adapted to different stages of functional recovery. PMID- 21977191 TI - Generic Substitution Issues: Brand-generic Substitution, Generic-generic Substitution, and Generic Substitution of Narrow Therapeutic Index (NTI)/Critical Dose Drugs. AB - Doctors accuse individual variability or lack of quality of generic drugs for adverse reactions or lack of efficacy. The variability of effect of generic substitution, although accepted by clinicians as possible, is little discussed or even understood by them. The situation is really serious in the case of generic substitution of drugs with narrow therapeutic index (NTI) or critical dose. In this paper we review the basic notions of variability and effectiveness of generic medication and change of attitude that would improve the use of these drugs. PMID- 21977190 TI - Gastrointestinal manifestations in systemic autoimmune diseases. AB - In an autoimmune disease, the immune system attacks and harms the body's own tissues. The systemic autoimmune diseases include collagen vascular diseases, the systemic vasculitides, Wegener granulomatosis, and Churg-Strauss syndrome. These disorders can involve any part of the gastrointestinal tract, hepatobiliary system and pancreas. They can cause a variety of gastrointestinal manifestations that are influenced by the pathophysiologic characteristics of the underlying disease process. There is a wide variation of gastrointestinal manifestations from these autoimmune disorders including, but not limited to: oral ulcers, dysphagia, gastroesophageal reflux disease, abdominal pain, constipation, diarrhea, fecal incontinence, pseudo-obstruction, perforation and gastrointestinal bleeding. Clinical workup should be initiated by the patient's subjective complaints. In this review, we analyze the effects of autoimmune diseases on the gastrointestinal tract. PMID- 21977192 TI - Update in dermatology. PMID- 21977193 TI - Update in rheumatology. PMID- 21977194 TI - Update in hematology. PMID- 21977195 TI - Update in neurology. PMID- 21977196 TI - Update in psychiatry. PMID- 21977197 TI - Update in obstetrics and gynecology. PMID- 21977198 TI - Update in orthopedics. PMID- 21977199 TI - Update in surgery. PMID- 21977200 TI - Update in genetics. PMID- 21977201 TI - Convergent synthesis of the tetrasaccharide repeating unit of the O-antigen of Shigella boydii type 9. AB - A convenient synthesis of the tetrasaccharide repeating unit of the O-antigen of Shigella boydii type 9 has been achieved in excellent yield using a [2 + 2] block glycosylation strategy. TEMPO-mediated selective oxidation of the primary alcohol of the tetrasaccharide derivative 8 to the carboxylic group followed by deprotection of the functional groups furnished target tetrasaccharide 1 as its 4 methoxyphenyl glycoside in high yield. PMID- 21977202 TI - Lithium phosphonate umpolung catalysts: Do fluoro substituents increase the catalytic activity? AB - Fluorinated and nonfluorinated phosphonates are employed as precatalysts in lithium phosphonate catalyzed cross benzoin couplings. Surprisingly, a decreased catalytic activity for the fluorinated precatalysts compared to the nonfluorinated systems is observed. Furthermore, the ring size of six, seven and nine membered ring catalysts appears not to be crucial for their catalytic activity. PMID- 21977203 TI - Gold(I)-catalyzed synthesis of gamma-vinylbutyrolactones by intramolecular oxaallylic alkylation with alcohols. AB - Gold(I)-N-heterocyclic carbene (NHC) complexes proved to be a reliable catalytic system for the direct synthesis of functionalized gamma-vinylbutyrolactones by intramolecular oxaallylic alkylation with primary alcohols. Good isolated chemical yields were obtained for a range of malonyl and acetate derivatives. The good performance in reagent-grade solvents and the functional group/moisture tolerance make this catalytic process a promising route for the synthesis of architecturally complex polycyclic structures. PMID- 21977204 TI - NMR studies of anion-induced conformational changes in diindolylureas and diindolylthioureas. AB - The conformational properties of 1,3-diindolylureas and thioureas were studied by a combination of heteronuclear NMR spectroscopy and quantum mechanics calculations. NOE experiments showed that the anti-anti conformer along the C7 N7alpha bonds was predominant in DMSO-d(6) solution in the absence of anions. Anion-induced changes in the (1)H and (15)N chemical shifts confirm the weak binding of chloride anions with negligible conformational changes. Strong deshielding of ureido protons and moderate deshielding of indole NH was observed upon the addition of acetate, benzoate, bicarbonate and dihydrogen phosphate, which indicated that the predominant hydrogen bond interactions occurred at the urea donor groups. Binding of oxo-anions caused conformational changes along the C7-N7alpha bonds and the syn-syn conformer was preferred for anion-receptor complexes. The conformational changes upon anion binding are in good agreement with energetic preferences established by ab initio calculations. PMID- 21977205 TI - Directed aromatic functionalization. PMID- 21977206 TI - A simple and convenient one-pot synthesis of substituted isoindolin-1-ones via lithiation, substitution and cyclization of N'-benzyl-N,N-dimethylureas. AB - Lithiation of N'-benzyl-N,N-dimethylurea and its substituted derivatives with t BuLi (3.3 equiv) in anhydrous THF at 0 degrees C followed by reaction with various electrophiles afforded a range of 3-substituted isoindolin-1-ones in high yields. PMID- 21977207 TI - Selectivity in C-alkylation of dianions of protected 6-methyluridine. AB - A regioselective synthesis of 6-omega-alkenyluridines 3, precursors of potent antiviral and antitumor cyclonucleosides 5, is described. While omega-alkenyl halides do not alkylate 6-lithiouridine, compounds 3 were prepared in a regioselective manner by sequential treatment of 6-methyluridine 2 with LTMP or LDA (4 equiv) in THF at -30 degrees C followed by alkylation with omega-alkenyl bromides. PMID- 21977208 TI - Meta-metallation of N,N-dimethylaniline: Contrasting direct sodium-mediated zincation with indirect sodiation-dialkylzinc co-complexation. AB - Previously we reported that direct zincation of N,N-dimethylaniline by the mixed metal zincate reagent 1 ((TMEDA)Na(TMP)(t-Bu)Zn(t-Bu)) surprisingly led to meta metallation (zincation) of the aniline, as manifested in the crystalline complex 2 ((TMEDA)Na(TMP)(m-C(6)H(4)-NMe(2))Zn(t-Bu)), and that iodination of these isolated crystals produced the meta-isomer N,N-dimethyl-3-iodoaniline quantitatively. Completing the study here we find that treating the reaction solution with iodine produces a 72% conversion and results in a mixture of regioisomers of N,N-dimethyliodoaniline, with the meta-isomer still the major product (ortho:meta:para ratio, 6:73:21), as determined by NMR. In contrast to this bimetallic method, sodiation of N,N-dimethylaniline with n-BuNa produced the dimeric, ortho-sodiated complex 3 (((TMEDA)Na(o-C(6)H(4)-NMe(2)))(2)), as characterised by X-ray crystallography and NMR. No regioisomers were observed in the reaction solution. Introducing t-Bu(2)Zn to this reaction solution afforded a cocrystalline product in the solid-state, composed of the bis-anilide 4 ((TMEDA)Na(o-C(6)H(4)-NMe(2))(2)Zn(t-Bu)) and the Me(2)N-C cleavage product 5 ({(TMEDA)(2)Na}(+){(t-Bu(2)Zn)(2)(u-NMe(2))}(-)), which was characterised by X ray crystallography. NMR studies of the reaction mixture that produces 4 and 5 revealed one additional species, but the mixture as a whole contained only ortho species and a trace amount of para-species as established by iodine quenching. In an indirect variation of the bimetallic reaction, TMP(H) was added at room temperature to the reaction mixture that afforded 4 and 5. This gave the crystalline product 6 ((TMEDA)Na(TMP)(o-C(6)H(4)-NMe(2))Zn(t-Bu)), the ortho isomer of the meta-complex 2, as determined from X-ray crystallographic and NMR data. Monitoring the regioselectivity of the reaction by iodination revealed a 16.6:1.6:1.0 ortho:meta:para ratio. Interestingly, when the TMP(H) containing solution was heated under reflux for 18 hours more meta-isomer was produced (corresponding ratio 3.7:4.2:1.0). It is likely that this change has its origin in a retro reaction that produces the original base 1 as an intermediate. Theoretical calculations at the DFT level using the B3LYP method and the 6-311G** basis set were used to probe the energetics of both monometallic and bimetallic systems. In accord with the experimental results, it was found that ortho metallation was favoured by sodiation; whereas meta- (closely followed by para-) metallation was favoured by direct sodium-mediated zincation. PMID- 21977209 TI - Use of mixed Li/K metal TMP amide (LiNK chemistry) for the synthesis of [2.2]metacyclophanes. AB - A new two-step general approach to [2.2]metacyclophane synthesis from substituted m-xylenes is described. The strategy employs a selective benzylic metalation and oxidative C-C bond formation for both synthetic operations. Regioselective benzylic metalation is achieved using the BuLi, KOt-Bu, TMP(H) (2,2,6,6 tetramethylpiperidine) combination (LiNK metalation conditions) and oxidative coupling with 1,2-dibromoethane. The synthetic ease of this approach compares favourably with previously reported methods and allows for ready access to potentially useful planar chiral derivatives. PMID- 21977210 TI - Combined directed ortho-zincation and palladium-catalyzed strategies: Synthesis of 4,n-dimethoxy-substituted benzo[b]furans. AB - A new route to regioselectively dialkoxy-functionalized benzo[b]furan derivatives has been developed from 3-halo-2-iodoanisoles bearing an additional methoxy group, which have been accessed through an ortho-zincation/iodination reaction. Two palladium-catalyzed processes, namely a Sonogashira coupling followed by a tandem hydroxylation/cyclization sequence, give rise to new and interesting dimethoxy-substituted benzo[b]furans. PMID- 21977211 TI - Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents. AB - In this review we summarize the most important procedures for the preparation of functionalized organzinc and organomagnesium reagents. In addition, new methods for the preparation of polyfunctional aryl- and heteroaryl zinc- and magnesium compounds, as well as new Pd-catalyzed cross-coupling reactions, are reported herein. Experimental details are given for the most important reactions in the Supporting Information File 1 of this article. PMID- 21977212 TI - Bromine-lithium exchange: An efficient tool in the modular construction of biaryl ligands. AB - Regioselective bromine-lithium exchange reactions on polybrominated biaryls enable the modular synthesis of various polysubstituted biphenyls such as bis(dialkylphosphino)-, bis(diarylphosphino)- and dialkyl(diaryl)phosphinobiphenyls. All permutations of substituents at the ortho positions of the biphenyls are possible. In a similar manner, one can gain access to monophosphine analogues. So far, such a process, based on the effective discrimination between bromine atoms as a function of their chemical environment, has been observed only sporadically. PMID- 21977213 TI - Koch-Haaf reaction of adamantanols in an acid-tolerant hastelloy-made microreactor. AB - The Koch-Haaf reaction of adamantanols was successfully carried out in a microflow system at room temperature. By combining an acid-tolerant hastelloy made micromixer, a PTFE tube, and a hastelloy-made microextraction unit, a packaged reaction-to-workup system was developed. By means of the present system, the multigram scale synthesis of 1-adamantanecarboxylic acid was achieved in ca. one hour operation. PMID- 21977214 TI - Synthesis of diverse dihydropyrimidine-related scaffolds by fluorous benzaldehyde based Biginelli reaction and post-condensation modifications. AB - Dihydropyrimidinones and dihydropyrimidinethiones generated from the Biginelli reactions of perfluorooctanesulfonyl-attached benzaldehydes are used as common intermediates for post-condensation modifications such as cycloaddition, Liebeskind-Srogl reaction and Suzuki coupling to form biaryl-substituted dihydropyrimidinone, dihydropyrimidine, and thiazolopyrimidine compounds. The high efficiency of the diversity-oriented synthesis is achieved by conducting a multicomponent reaction for improved atom economy, under microwave heating for fast reaction, and with fluorous solid-phase extractions (F-SPE) for ease of purification. PMID- 21977215 TI - A straightforward approach towards combined alpha-amino and alpha-hydroxy acids based on Passerini reactions. AB - Complex amino acids with an alpha-acyloxycarbonyl functionality in the side chain are easily available through epoxide opening by chelated enolates and subsequent oxidation/Passerini reaction. This protocol works with both, aldehyde and ketone intermediates, as long as the ketones are activated by electron-withdrawing groups. In principle Ugi reactions are also possible, allowing the generation of diamino acid derivatives. PMID- 21977216 TI - Welcome to the JOCB Bulletin. PMID- 21977217 TI - Urinary incontinence in children. AB - BACKGROUND: Urinary incontinence (bedwetting, enuresis) is the commonest urinary symptom in children and adolescents and can lead to major distress for the affected children and their parents. Physiological and non-physiological types of urinary incontinence are sometimes hard to tell apart in this age group. METHODS: This article is based on selected literature retrieved by a PubMed search and on an interdisciplinary expert consensus. RESULTS AND CONCLUSION: Nocturnal enuresis has a variety of causes. The main causative factors in monosymptomatic enuresis nocturna (MEN) are an impaired ability to wake up when the bladder is full, due to impaired or absent perception of fullness during sleep, and an imbalance between bladder capacity and nocturnal urine production. On the other hand, non monosymptomatic enuresis nocturna (non-MEN) is usually traceable to bladder dysfunction, which is also the main cause of diurnal incontinence. A basic battery of non-invasive diagnostic tests usually suffices to determine which type of incontinence is present. Further and more specific testing is indicated if an organic cause is suspected or if the treatment fails. The mainstay of treatment is urotherapy (all non-surgical and non-pharmacological therapeutic modalities). Some patients, however, will need supportive medication in addition. Urinary incontinence has different causes in children and adults and must therefore be diagnosed and treated differently as well. All physicians who treat the affected children (not just pediatricians and family doctors, but also pediatric nephrologists, urologists, pediatric surgeons, and child psychiatrists) must be aware of the specific features of urinary incontinence in childhood. PMID- 21977218 TI - Cardiovascular diseases in pregnancy. Not helpful. PMID- 21977220 TI - Inherited cardiac arrhythmias: diagnosis, treatment, and prevention. AB - BACKGROUND: The incidence of sudden cardiac death in persons under age 40 is roughly 3 per 100 000 persons per year in Germany and North America. Many of these deaths are found to be due to hereditary heart diseases, often a primary structural heart disease associated with arrhythmia or else a primary arrhythmia syndrome in a structurally normal heart. Such diseases are usually of autosomal dominant inheritance, often affect otherwise healthy persons, and can generally be well treated if recognized early. Patients commonly have affected relatives who are still asymptomatic. METHODS: This review is based on articles up to May 2010 that were retrieved by a selective search of the Medline database via PubMed, with additional consideration of the relevant European and American guidelines and the German Law on Genetic Diagnosis. RESULTS AND CONCLUSION: Hereditary arrhythmia syndromes are now found in more than half of all initially unexplained cases of sudden cardiac death in young persons. Among such cases, the hereditary arrhythmia syndrome is primary in 70% and caused by an arrhythmogenic structural heart disease in 30%. In addition to autopsy findings, a thorough family history, relevant medical findings obtained during life (if available), the examination of relatives, and directed molecular testing where appropiate enabled establishing the diagnosis. Arrthymia syndromes that can cause sudden death are often detectable during life if physicians and the public are appropriately sensitized. PMID- 21977225 TI - New insights on the management of wildlife diseases using multi-state recapture models: the case of classical swine fever in wild boar. AB - BACKGROUND: The understanding of host-parasite systems in wildlife is of increasing interest in relation to the risk of emerging diseases in livestock and humans. In this respect, many efforts have been dedicated to controlling classical swine fever (CSF) in the European Wild Boar. But CSF eradication has not always been achieved even though vaccination has been implemented at a large scale. Piglets have been assumed to be the main cause of CSF persistence in the wild since they appeared to be more often infected and less often immune than older animals. However, this assumption emerged from laboratory trials or cross sectional surveys based on the hunting bags. METHODOLOGY/PRINCIPAL FINDINGS: In the present paper we conducted a capture-mark-recapture study in free-ranging wild boar piglets that experienced both CSF infection and vaccination under natural conditions. We used multi-state capture recapture models to estimate the immunization and infection rates, and their variations according to the periods with or without vaccination. According to the model prediction, 80% of the infected piglets did not survive more than two weeks, while the other 20% quickly recovered. The probability of becoming immune did not increase significantly during the summer vaccination sessions, and the proportion of immune piglets was not higher after the autumn vaccination. CONCLUSIONS/SIGNIFICANCE: Given the high lethality of CSF in piglets highlighted in our study, we consider unlikely that piglets could maintain the chain of CSF virus transmission. Our study also revealed the low efficacy of vaccination in piglets in summer and autumn, possibly due to the low palatability of baits to that age class, but also to the competition between baits and alternative food sources. Based on this new information, we discuss the prospects for the improvement of CSF control and the interest of the capture-recapture approach for improving the understanding of wildlife diseases. PMID- 21977221 TI - New perspectives on adolescent motivated behavior: attention and conditioning. AB - Adolescence is a critical transition period, during which fundamental changes prepare the adolescent for becoming an adult. Heuristic models of the neurobiology of adolescent behavior have emerged, promoting the central role of reward and motivation, coupled with cognitive immaturities. Here, we bring focus to two basic sets of processes, attention and conditioning, which are essential for adaptive behavior. Using the dual-attention model developed by Corbetta and Shulman (2002), which identifies a stimulus-driven and a goal-driven attention network, we propose a balance that favors stimulus-driven attention over goal driven attention in youth. Regarding conditioning, we hypothesize that stronger associations tend to be made between environmental cues and appetitive stimuli, and weaker associations with aversive stimuli, in youth relative to adults. An attention system geared to prioritize stimulus-driven attention, together with more powerful associative learning with appetitive incentives, contribute to shape patterns of adolescent motivated behavior. This proposed bias in attention and conditioning function could facilitate the impulsive, novelty-seeking and risk-taking behavior that is typical of many adolescents. PMID- 21977226 TI - The biological basis of a universal constraint on color naming: cone contrasts and the two-way categorization of colors. AB - Many studies have provided evidence for the existence of universal constraints on color categorization or naming in various languages, but the biological basis of these constraints is unknown. A recent study of the pattern of color categorization across numerous languages has suggested that these patterns tend to avoid straddling a region in color space at or near the border between the English composite categories of "warm" and "cool". This fault line in color space represents a fundamental constraint on color naming. Here we report that the two way categorization along the fault line is correlated with the sign of the L- versus M-cone contrast of a stimulus color. Moreover, we found that the sign of the L-M cone contrast also accounted for the two-way clustering of the spatially distributed neural responses in small regions of the macaque primary visual cortex, visualized with optical imaging. These small regions correspond to the hue maps, where our previous study found a spatially organized representation of stimulus hue. Altogether, these results establish a direct link between a universal constraint on color naming and the cone-specific information that is represented in the primate early visual system. PMID- 21977227 TI - Looking the part: social status cues shape race perception. AB - It is commonly believed that race is perceived through another's facial features, such as skin color. In the present research, we demonstrate that cues to social status that often surround a face systematically change the perception of its race. Participants categorized the race of faces that varied along White-Black morph continua and that were presented with high-status or low-status attire. Low status attire increased the likelihood of categorization as Black, whereas high status attire increased the likelihood of categorization as White; and this influence grew stronger as race became more ambiguous (Experiment 1). When faces with high-status attire were categorized as Black or faces with low-status attire were categorized as White, participants' hand movements nevertheless revealed a simultaneous attraction to select the other race-category response (stereotypically tied to the status cue) before arriving at a final categorization. Further, this attraction effect grew as race became more ambiguous (Experiment 2). Computational simulations then demonstrated that these effects may be accounted for by a neurally plausible person categorization system, in which contextual cues come to trigger stereotypes that in turn influence race perception. Together, the findings show how stereotypes interact with physical cues to shape person categorization, and suggest that social and contextual factors guide the perception of race. PMID- 21977229 TI - Role of Oxytocin in deceleration of early atherosclerotic inflammatory processes in adult male rats. AB - OBJECTIVE: The study aimed to examine the effect of exogenous OT administration on the inflammation and atherosclerosis in adult male rats and its possible mechanisms. Thirty adult male rats equally divided into three groups. Control group fed regular diet; group II fed control diet supplemented with L-methionine for 10 weeks. Group III received L-methionine and oxytocin treatment for 10 weeks. RT-PCR analysis showed that OT administration increased oxytocin receptor mRNA (2 fold, P, 0.05). Blood samples were evaluated for total homocysteine, interlukin-6 (IL-6), monocyte chemoatrratant protein-1 (MCP-1) and C-reactive protein (CRP) by ELIZA, lipid profile, nitric oxide (NO), malondialdehyde (MDA) and reduced glutathione (GSH) were determined. Specimens from aorta were processed for immunohistochemical staining for Aorta nuclear factor _B (NF kappaB) p65 protein. Result showed that OT administration to group III decreased the plasma levels IL-6, MCP-1 and CRP levels which were elevated in group II. Moreover, there was decrease of the oxidative stress of group III in terms of increased plasma levels of NO and GSH and decreased plasma levels of MDA in blood. In addition, rats of group II showed histological abnormalities manifested by thickening and ulceration of the aortic wall. Marked increased expression of NF-kappaB in aorta of in group II was detected. However, OT administration restores the histological structure of the aorta and decreased the expression of NF-kappaB in aorta of group III similar to the control group. CONCLUSION: OT has anti inflammatory pathway in atherosclerosis as it decelerates atherosclerosis by decreasing the proinflammatory responses through many mechanisms, mainly the up regulation of its receptors. PMID- 21977228 TI - MIF participates in Toxoplasma gondii-induced pathology following oral infection. AB - BACKGROUND: Macrophage migration inhibitory factor (MIF) is essential for controlling parasite burden and survival in a model of systemic Toxoplasma gondii infection. Peroral T. gondii infection induces small intestine necrosis and death in susceptible hosts, and in many aspects resembles inflammatory bowel disease (IBD). Considering the critical role of MIF in the pathogenesis of IBD, we hypothesized that MIF participates in the inflammatory response induced by oral infection with T. gondii. METHODOLOGY/PRINCIPAL FINDINGS: Mif deficient (Mif(-/ )) and wild-type mice in the C57Bl/6 background were orally infected with T. gondii strain ME49. Mif(-/-) mice had reduced lethality, ileal inflammation and tissue damage despite of an increased intestinal parasite load compared to wt mice. Lack of MIF caused a reduction of TNF-alpha, IL-12, IFN-gamma and IL-23 and an increased expression of IL-22 in ileal mucosa. Moreover, suppressed pro inflammatory responses at the ileal mucosa observed in Mif(-/-) mice was not due to upregulation of IL-4, IL-10 or TGF-beta. MIF also affected the expression of matrix metalloproteinase-9 (MMP-9) but not MMP-2 in the intestine of infected mice. Signs of systemic inflammation including the increased concentrations of inflammatory cytokines in the plasma and liver damage were less pronounced in Mif(-/-) mice compared to wild-type mice. CONCLUSION/SIGNIFICANCE: In conclusion, our data suggested that in susceptible hosts MIF controls T. gondii infection with the cost of increasing local and systemic inflammation, tissue damage and death. PMID- 21977230 TI - Differential expression of TLR2, TLR4 and JNK in mucosa of ileal pouches for ulcerative colitis. Is there a role for bacterial antigen pathway in asymptomatic patients? AB - INTRODUCTION: Ileal pouch-anal anastomosis (IPAA) is the preferred surgical procedure for patients with refractory ulcerative colitis (UC) and familial adenomatous polyposis (FAP). However, pouchitis is the most common complication after IPAA in UC patients and only occurs after ileostomy closure. Therefore, it is important to get more information about the role of the ileal pouch microbiota and mucosa susceptibility to inflammation in UC patients. Therefore, we evaluated Toll-like receptors (TLRs) expression in normal endoscopic and histological mucosa of the ileal pouch in patients with UC and FAP, in order to find any abnormality in this pathway in asymptomatic patients, which may contribute to pouchitis. MATERIALS AND METHODS: Twelve patients (six with UC and six with FAP) with "J" pouch reconstruction, after total rectocolectomy, were studied. Biopsies were obtained from the mucosa of the pouch. Normal ileum biopsies were obtained from six patients submitted to ileocolonoscopy with no abnormalities. The specimens were snap-frozen and the expressions of TLR2, TLR4 and JNK (nuclear signalization factor) were determined by immunoblot protein extract. RESULTS: Patients with UC had significantly higher protein levels of TLR4 than controls and FAP. The expressions of TLR2 and JNK were similar in the groups. CONCLUSION: Patients with UC had higher levels of TLR4, even in the absence of clinical, endoscopic and histological pouchitis. These findings may explain a tendency towards the up-regulation of intracellular pathways activated by bacterial antigens in UC patients, which could contribute to the production of proinflammatory mediators and pouchitis development. PMID- 21977231 TI - Functional characterization of mutations in the promoter proximal region of the telomerase hTERC gene identified in patients with hematological disorders. AB - Telomerase RNA gene (hTERC) mutations have been identified in a subset of patients with bone-marrow failure syndromes (BMFS). While most of the mutations were found in the coding region of hTERC, some rare disease-associated mutations as well as polymorphic sequence changes were found in the promoter proximal region of the gene, including the -99C/G sequence change that was thought to modulate hTERC gene expression by disrupting Sp1 transcriptional factor binding [1]. We and other researchers recently identified, in addition to the -99C/G mutation, several other sequence variations (-240delCT, -714+C insertion, and 771A/G) in the hTERC promoter in other cohorts of patients with blood disorders. Using a convenient telomerase reconstitution assay coupled with the hTERC promoter driven luciferase reporter assay, we characterized each of the hTERC's promoter sequence variants and found that these rare sequence changes did not negatively affect telomerase gene expression or function. We therefore conclude that all known mutations in the promoter proximal region of the hTERC gene to date do not necessarily contribute to the pathogenesis of hematological disorders by directly affecting telomerase transcriptional activity and/or its enzymatic function. PMID- 21977232 TI - Sequential adaptation in latent tuberculosis bacilli: observation by atomic force microscopy (AFM). AB - Mycobacterium tuberculosis (MTB) can persist within the human host for years without causing disease, in a syndrome known as latent tuberculosis. The mechanisms by which M. tuberculosis establishes a latent metabolic state is unknown, but it is hypothesized that reduced oxygen tension may trigger the bacillus to enter a state of latency. Therefore, we are studying anaerobic culture of M. tuberculosis (H37RV) as a model of latency. For the first time, the sequential adaptation of latent bacilli (every 90 days for 48 months) viewed under Atomic Force Microscopy (AFM). Two types of adaptation were observed and are described here. First, cells are undergoing temporary adaptation (from 1 to 18 months of latency) that includes; thickening of cell wall (20.5+/-1.8 nm versus 15.2+/-1.8 nm, P<0.05), formation of ovoid cells by "folding phenomena"(65 70%), size reduction (0.8+/-0.1 MUm versus 2.5+/-0.5 MUm), and budding type of cell division (20-25%).A second feature include changes that accompany development of specialized cells i.e., production of spore like cells (0.5+/-0.2 MUm) and their progeny (filterable non -acid fast forms; 150 to 300 MUm in size). Although, these cells were not real spore because they fail to form a heat resistant colony forming units, after incubation for 35-40 min at 65 degrees C. The filterable non-acid fast forms of bacilli are metabolically active and increased their number by symmetrical type of cell-division. Therefore, survival strategies that developed by M. tuberculosis under oxygen limited condition are linked to its shape, size and conspicuous loss of acid fastness. PMID- 21977233 TI - Frequencies of HFE gene mutations associated with haemochromatosis in the population of Libya living in Benghazi. AB - THE STUDIES OF THE HFE MUTATIONS: H63D and C282Y in North African populations have revealed the extreme rarity or even the absence of the C282Y mutation. We have examined 200 chromosomes (100 Libyan people live in Benghazi) for the presence of the two HFE mutations by PCR-RFLP analysis by using PCR conditions used to amplify both Autosomal and Y chromosomal STRs. We have found that the allele frequencies are, respectively, 17% for the H63D and 0% for the C282Y. These results are consistent with the worldwide spread of the H63D mutation and the north European restriction of the C282Y. PMID- 21977234 TI - Patients' subjective visual experiences during vitreous surgery under local anesthesia. AB - OBJECTIVE: To investigate patient's visual experience during vitreous surgery under local anesthesia. METHODS: A prospective and randomized study of 76 patients that underwent vitreous surgeries in our hospital between July 2010 and December 2010 was designed. All patients were interviewed half an hour before and within 1 hour after the surgery using a standardized questionnaire. Basic characteristics of patients and their intraoperative visual experiences like light, color, moving object, pain, fear, and the desire for general anesthesia before and after the surgery were recorded. RESULTS: Sixty patients (78.9%) perceived at least light perception, and 16 patients (21.1%) got no light perception throughout the entire duration of the operation. Forty one patients (53.9%) perceived only light, while 19 patients (25%) experienced moving objects. Thirty nine patients (51.3%) were frightened during their intraoperative visual experiences. Patients with better preoperative best-corrected visual acuity (BCVA) were more likely to be frightened (p=0.002). The frightened experience was affected notably by the different perceptions during operation, moving object (p=0.024), light (p=0.071), and color (p=0.071). Patients below 50 years old, especially from 20 to 30, were more likely to choose general anesthesia after the vitreous surgery. CONCLUSIONS: Most patients (78.9%) experienced at least light perception during the vitreous surgery under local anesthesia. There were no significant differences between the various visual experiences and their basic characteristics. Patients with better preoperative BCVA, perceived moving objects in their visual sensations seemed more likely to be frightened. PMID- 21977235 TI - Tendon repair augmented with a novel circulating stem cell population. AB - Tendon ruptures are common sports-related injuries that are often treated surgically by the use of sutures followed by immobilization. However, tendon repair by standard technique is associated with long healing time and often suboptimal repair. Methods to enhance tendon repair time as well as the quality of repair are currently unmet clinical needs. Our hypothesis is that the introduction of a unique stem cell population at the site of tendon transection would result in an improved rate and quality of repair. Achilles tendons of fifty one Sprague-Dawley rats were transected and suture-repaired. In half of the rats, a biodegradable scaffold seeded with allogenic circulating stem cells was placed as an onlay to the defect site in addition to the suture repair. The other half was treated with suture alone to serve as the control group. Animals were randomized to a two-, four-, or six-week time group. At the time of necropsy, tendons were harvested and prepared for either biomechanical or histological analysis. Histological slides were evaluated in a blinded fashion with the use of a grading scale. By two weeks, the experimental group demonstrated a significant improvement in repair compared to controls with no failures. Average histological scores of 0.6 and 2.6 were observed for the experimental and control group respectively. The experimental group demonstrated complete bridging of the transection site with parallel collagen fiber arrangement. By four weeks, both groups showed a continuing trend of healing, with the scaffold group exceeding the histological quality of the tissue repaired with suture alone. Biomechanically, the experimental group had a decreasing cross-sectional area with time which was also associated with a significant increase in the ultimate tensile strength of the tendons, reaching 4.2MPa by six weeks. The experimental group also achieved a significantly higher elastic toughness by six weeks and saw an increase in the tensile modulus, reaching 31Mpa by six weeks. The use of circulating stem cells as an adjunct in tendon repair demonstrates superior biomechanical properties and an improved level of histological organization, when compared to the suture alone control group. These improvements were not previously observed when gene therapy, protein therapy, or current tissue engineering technologies were used. PMID- 21977236 TI - Therapeutic strategies for complications secondary to hydatid cyst rupture. AB - OBJECTIVE: Clinical approach and therapeutic methods are important in cases with complicated hydatid cysts of the lung. This study was designed to retrospectively investigate cases with hydatid cysts, thereby discussing diagnostic methods, treatment modalities, and rates of morbidity and mortality in line with the literature. METHODS: 176 cases with perforated hydatid cysts, who presented to our clinic and underwent surgery between 2003 and 2011, were included in the study. There were 71 (40.34%) females and 105 males (59.66%) with a mean age of 27.80+/-14.07. The most common symptom was dyspnea (44.31%) and the most common radiological finding was the water lily sign (21.02%). 88.06% of the cases were surgically treated by Cystotomy+closure of bronchial opening+ capitonnage, 3.97% by wedge resection, 4.54% by segmentectomy and 3.40% by lobectomy. RESULTS: The cysts exhibited multiple localization in 24 cases (13.63%), bilateral localization in 14 cases (7.95%), with the most common localization (43.75%) being the right lower lobe. While the hydatid cyst rupture occurred due to delivery in three (1.70%), trauma in 11 (6.25%), and iatrogenic causes in seven (3.97%) cases, it occurred spontaneously in the rest of the cases (88.08%). Fourteen of the cases with spontaneously occurring rupture (7.95%) were detected to have received anthelmintic treatment for hydatid cyst during the preoperative period (albendazole). The rate of morbidity was 27.27% and the rate of mortality was 1.13% in our study. Two cases recurred during a one-year follow-up (1.13%). CONCLUSION: Hydatid cyst rupture should be considered in the differential diagnosis of cases with pleural effusion, empyema, pneumothorax and pneumonia occurring in endemic regions. Symptoms occurring during and after perforation lead to errors in differential diagnosis. Performing the surgery without delay favorably affects postoperative morbidity and mortality. While parenchyma preserving surgery is preferential, there is a need for resection in perforated hydatid cysts. PMID- 21977237 TI - Serum zinc levels in children of 0-24 months diagnosed with pneumonia admitted to our clinic. AB - AIM: We have planned to study the relationship between zinc (Zn) plasma levels, as well as pneumonia criteria, and zinc in healthy children younger than 2 years of age compared to pediatric patients diagnosed with pneumonia and admitted to a hospital. MATERIALS AND METHODS: The study enrolled 25 patients of 0-24 months referring to our hospital's pediatric clinic, who were then diagnosed with bronchopneumonia based on the World Health Organization diagnostic criteria and admitted to suckling children clinic due to inability to receive out-patient treatment, and 10 healthy children of the same age group, whose physical examinations revealed no pathological findings. RESULTS: There was no difference between the groups in terms of age and gender distribution (p> 0.05). The control group included in the study showed a significantly higher mean duration of breast milk intake compared to the patient groups (p<0.001). WBC values obtained from the patient group was significantly higher than that of the control group (p<0.001). Zn and iron (Fe) values as determined in the control group enrolled in the study were significantly higher compared to the patient group (p<0.01). Mean total protein in the control group was found to be significantly higher versus that of the patient groups (p<0.05). With regard to the r values of correlation coefficients of the subjects enrolled in the study, a slightly positive correlation was observed between Zn levels and iron levels (r=0.457). CONCLUSION: It was concluded that infections, particularly pneumonia, which present a serious issue both in our country and developing countries, may be developed more commonly among children with zinc deficiency. PMID- 21977238 TI - Ectopic secretion of parathyroid hormone in a neuroendocrine tumor: a case report and review of the literature. AB - Very few cases have been reported in which the production and secretion of intact PTH by a non-parathyroid tumor has been authenticated. This paper describes the case of a 73 year old white female with a clinical and biochemical profile characteristic of primary hyperparathyroidism. Sestamibi scan and comprehensive neck ultrasono-graphy failed to localize a cervical lesion. Because the clinical manifestations were striking, neck exploration was performed. Dissection of the central compartment identified a lesion. PTH levels dropped to normal within ten minutes after its removal. Intraoperative parathyroid hormone assays facilitated the successful surgical removal of the lesion. Pathological examination yielded a diagnosis of a neuroendocrine tumor. These results document the ectopic production of intact PTH by a neuroendocrine tumor and present a novel neoplastic cause of primary hyperparathyroidism. This is the second report of an ectopic neuroendocrine tumor in the head and neck which secreted intact PTH. PMID- 21977239 TI - A Pilot Study of the ELFE Longitudinal Cohort: Feasibility and Preliminary Evaluation of Biological Collection. AB - Etude Longitudinale Francaise depuis l'Enfance (ELFE) will be a national French cohort of 20,000 children followed from birth to adulthood. Biological samples will be taken at birth to evaluate the fetal exposition to several substances. A pilot study was carried out in October 2007 to test the preanalytical factors that affected sample quality. A variety of fractions were collected by the midwife after delivery from different blood collection tubes. Options in the collection process were 2 daily transports of samples, centralized and standardized processing methodology, and storage of multiple aliquots in liquid nitrogen or at -80 degrees C. We analyzed preanalytical factors that could have affected coagulation and then soluble CD40 Ligand (sCD40L) as a quality control tool for serum quality. Cord blood and urine were collected from 82% and 84% of women, respectively, who agreed to be followed up in the ELFE project. The use of syringe was the main factor correlated with coagulation (relative risk: 2.79 [1.47; 5.31], P<0.01). Maternity unit status was also associated with coagulation (RR: 1.48 [1.03; 2.13] in a private maternity unit vs. a public maternity) as well as time between collection and centrifugation (RR 1.03 [1; 1.07] when time between collection and centrifugation increases from 1 h). There were no extremely low sCD40L values indicating extreme exposures to room temperatures. This first evaluation study allowed us to stress the importance of carefully recording all potentially critical preanalytical variables that might be used at a large-scale level. PMID- 21977240 TI - Standardized Serum-Free Cryomedia Maintain Peripheral Blood Mononuclear Cell Viability, Recovery, and Antigen-Specific T-Cell Response Compared to Fetal Calf Serum-Based Medium. AB - The ability to analyze cryopreserved peripheral blood mononuclear cells (PBMCs) from biobanks for antigen-specific T-cell immunity is necessary to evaluate responses to immune-based therapies. Comprehensive studies have demonstrated that the quality of frozen PBMCs is critical and the maintenance of cell viability and functionality by using appropriate cryopreservation techniques is a key to the successful outcome of assays using PBMCs. Different cryomedia additives affect cell viability. The most common additive is fetal calf serum (FCS), although it is widely known that each FCS lot has to be tested before usage to prevent nonspecific stimulation of T-cells. Also, shipping of samples containing FCS is critical because of many import restrictions. Often, dimethyl sulfoxide (DMSO) is added as a cryoprotectant. However, DMSO concentration has to be reduced significantly because of its toxic effect on cells at room temperature. Therefore, we have developed freezing approaches to minimize cytotoxicity of cryoprotectants and maintain T-cell functionality. We compared different additives to the widely used FCS and found bovine serum albumin fraction V to be an appropriate substitute for the potentially immune-modulating FCS. We also found that DMSO concentration can be reduced by the addition of hydroxyethyl starch. Using our serum-free cryomedia, the PBMC recovery was more than 83% and the PBMC viability was more than 98%. Also, the T-cell functionality measured by enzyme-linked immunospot (ELISpot) was optimal after cryopreservation with our new cryomedia. On the basis of our experimental results, we could finally design 2 different, fully working cryomedia that are standardized, serum free, and manufactured under GMP conditions. PMID- 21977241 TI - Variation of Peripheral Blood Mononuclear Cell RNA Quality in Archived Samples. AB - The Infectious Diseases BioBank (IDB) has consistently archived peripheral blood mononuclear cell (PBMNC) RNA for transcriptome analyses. RNA is particularly labile, and hence, these samples provide a sensitive indicator for assessing the IDB's quality-assurance measures. Independent analyses of 104 PBMNC RNA specimens from 26 volunteers revealed that the mean RNA integrity number (RIN) was high (9.02), although RIN ranged between scores of 7 and 10. This variation of RIN values was not associated with ischemic time, PBMNC quality, number of samples processed per day, self-medication after immunization, freezer location, donor characteristics, differential white blood cell counts, or daily variation in RNA extractions (all P>0.05). RIN values were related to the date of collection, with those processed during mid-summer having highest RIN scores (P=0.0001). Amongst specimens with the lowest RIN scores, no common feature could be identified. Thus, no technical explanation for the variation in RNA quality could be ascertained and these may represent normal physiological variations. These data provide strong evidence that current IDB protocols for the isolation and preservation PBMNC RNA are robust. PMID- 21977242 TI - Willingness to Donate Human Samples for Establishing a Dermatology Research Biobank: Results of a Survey. AB - There is a rising need for biomaterial in dermatological research with regard to both quality and quantity. Research biobanks as organized collections of biological material with associated personal and clinical data are of increasing importance. Besides technological/methodological and legal aspects, the willingness to donate samples by patients and healthy volunteers is a key success factor. To analyze the theoretical willingness to donate blood and skin samples, we developed and distributed a questionnaire. Six hundred nineteen questionnaires were returned and analyzed. The willingness to donate samples of blood (82.5%) and skin (58.7%) is high among the population analyzed and seems to be largely independent of any expense allowance. People working in the healthcare system, dermatological patients, and higher qualified individuals seem to be in particular willing to donate material. An adequate patient insurance as well as an extensive education about risks and benefits is requested. In summary, there is a high willingness to donate biological samples for dermatological research. This theoretical awareness fits well with our own experiences in establishing such a biobank. PMID- 21977243 TI - How Representative Are Research Tissue Biobanks of the Local Populations? Experience of the Infectious Diseases Biobank at King's College, London, UK. AB - Biobanks have a primary responsibility to collect tissues that are a true reflection of their local population and thereby promote translational research, which is applicable to the community. The Infectious Diseases BioBank (IDB) at King's College London is located in the southeast of the city, an area that is ethnically diverse. Transplantation programs have frequently reported a low rate of donation among some ethnic minorities. To determine whether patients who volunteered peripheral venous blood samples to the IDB were representative of the local community, we compared local government demographic data to characteristics of patients who have donated to the IDB. There was a good match between these statistics, indicating that the IDB's volunteer population of human immunodeficiency virus patients was similar to local demographics. PMID- 21977244 TI - Congenital complete atrioventricular block in the early pediatric population. AB - Congenital complete atrioventricular block (CCAVB) is a rare potentially lethal disease with an estimated incidence of 1 every 15.000 to 20.000 live born infants.IN STRUCTURALLY NORMAL HEARTS TWO KINDS OF CONGENITAL HEART BLOCK CAN BE IDENTIFIED: one usually diagnosed in utero associated with the circulating maternal anti-SS-A/Ro and anti-SS-B/La antibodies, the other kind is detected later in the neonatal period or during the infancy or childhood and present no clear relation with maternal antibodies. Nowadays, the diagnosis can be made in utero as early as between week 16 and 28 of gestation by foetal echocardiography.The mortality in isolated CCAVB is estimated between 8 and 16% and between 4 and 8% in children and adults. The mortality and morbidity of patients diagnosed outside the neonatal period is significantly lower than those with a in utero diagnosis.Risk factors for worse outcome in CCAVB are the foetal diagnosis, the presence of hydrops fetalis, delivery at 32 weeks gestation, and a ventricular rate <55 beats/min in early pregnancy (13,18).Aim of this review is to delineate the current knowledge on CCAVB presenting in children without structural heart disease including aetiology, outcome and management. Also outlined in this review are some of the problems still debated in this issue. PMID- 21977245 TI - Phosphate overload accelerates vascular aging in uremic patients. AB - Vascular calcification is a very common event in atients affected by diabetes and chronic kidney disease (CKD). Recently, it has been well documented that abnormalities in mineral and bone metabolism in CKD patients are associated with increased morbidity and mortality. Elevated serum phosphate and calcium-phosphate product levels play an important role in the pathogenesis of vascular mineralization in uremic patients and also appear to be associated with increased cardiovascular mortality. Together with classical passive precipitation of calcium-phosphate in soft tissues, during the last decade it has been demonstrated that inorganic phosphate may cause extraskeletal calcification directly through a real "ossification" of the tunica media in the vasculature of CKD patients. Therefore, control of phosphate retention is now an even more crucial target of treatment in patients affected by chronic kidney disease. PMID- 21977246 TI - Arrhythmic death and ICD implantation after myocardial infarction. AB - Arrhythmic death remains one of the most important causes of mortality after an acute myocardial infarction also in the revascularization era. As a consequence, identification of patients at risk should be performed before discharge. Unfortunately, in the clinical practice, this evaluation is mainly based on detection of a depressed left ventricular ejection. This approach, however, cannot adequately distinguish arrhythmic versus non-arrhythmic risk.This issue is of critical relevance when considering that arrhythmic death can be significantly reduced by appropriate interventions of implantable cardioverter defibrillator. Available evidence, however, indicates that in the first month after myocardial infarction, device implantation does not significantly reduce cardiac mortality: it seems that the reduction of arrhythmic death is counterbalanced by an increase in rate of death from non arrhythmic cause. It is therefore to be hoped that, in the future, arrhythmic risk evaluation will be based not only on the extent of left ventricular dysfunction but also on the analysis of other risk markers such as those reflecting autonomic dysfunction, cardiac electrical instability and presence of subclinical inflammation. PMID- 21977247 TI - Genetic bases of arrhythmogenic right ventricular Cardiomyopathy. AB - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disease in which the pathological substrate is a fibro-fatty replacement of the right ventricular myocardium. The major clinical features are different types of arrhythmias with a left branch block pattern. ARVC shows autosomal dominant inheritance with incomplete penetrance. Recessive forms were also described, although in association with skin disorders.Ten genetic loci have been discovered so far and mutations were reported in five different genes. ARVD1 was associated with regulatory mutations of transforming growth factor beta-3 (TGFbeta3), whereas ARVD2, characterized by effort-induced polymorphic arrhythmias, was associated with mutations in cardiac ryanodine receptor-2 (RYR2). All other mutations identified to date have been detected in genes encoding desmosomal proteins: plakoglobin (JUP) which causes Naxos disease (a recessive form of ARVC associated with palmoplantar keratosis and woolly hair); desmoplakin (DSP) which causes the autosomal dominant ARVD8 and plakophilin-2 (PKP2) involved in ARVD9. Desmosomes are important cell-to-cell adhesion junctions predominantly found in epidermis and heart; they are believed to couple cytoskeletal elements to plasma membrane in cell-to-cell or cell-to-substrate adhesions. PMID- 21977248 TI - Biventricular pacing and heterogeneity of ventricular repolarization in heart failure patients. AB - OBJECTIVE: The aim of our study was to evaluate the effect of cardiac resyncronization therapy (CRT) on QT dispersion (QTd), JT dispersion (JTd) and transmural dispersion of re-polarization (TDR), markers of heterogeneity of ventricular repolarization in a study population with severe heart failure. METHODS AND RESULTS: Fifty patients (43 male, 7 female, aged 60.2 +/- 3.1 years) suffering from congestive heart failure (N = 39 NYHA class III; N = 11 NYHA class IV) as a result of coronary artery disease (N = 19) or of dilated cardiomyopathy (N = 31), sinus rhythm, QRS duration >130 ms (mean QRS duration >156 +/- 21 ms), an ejection fraction < 35%, left ventricular end-diastolic diameter >55 mm, underwent permanent biventricular DDDR pacemaker implantation. A 12-lead standard electrocardiogram was performed at baseline, during right-, left-, and biventricular pacing and QTd, JTd and TDR were assessed. Biventricular pacing significantly reduced QTd (73.93 +/- 19.4 ms during BiVP vs 91 +/- 6.7 ms at sinus rhythm, p = 0.004), JTd (73.18 +/- 17.16 ms during BiVP vs 100.72 +/- 39.04 at baseline p = 0.003), TDR (93.16 +/- 15.60 vs 101.55 +/- 19.08 at baseline; p<0.004), as compared to sinus rhythm. Right ventricular endocardial pacing and left ventricular epicardial pacing both enhanced QTd (RVendoP 94 +/- 51 ms, p<0.03; LVepiP 116 +/-71 ms, p<0.02) and TDR (RVendoP 108.13 +/- 19.94 ms; p<0.002; LVepiP 114.71 +/- 26.1; p<0.05).There was no effect on JTd during right and left ventricular stimulation. CONCLUSIONS: Biventricular pacing causes a statistically significant reduction of ventricular heterogeneity of ripolarization and has an electrophysiological antiarrhythmic influence on arrhythmogenic substrate of dilatative cardiomiopathy. PMID- 21977249 TI - QT dispersion on ECG Holter monitoring and risk of ventricular arrhythmias in patients with dilated cardiomyopathy. AB - BACKGROUND: QT dispersion (QTd) is increased in patients with dilated cardiomyopathy. Increased QTd has been associated with the risk of sudden death. We studied: a) the relation between QTd on 12-lead ECG and QTd-ECG Holter; b) the relation between QTd apex (QTda) and QTd end (QTde) on ECG Holter and the risk of ventricular arrhythmias in patients with dilated cardiomyopathy. METHODS AND RESULTS: 65 patients with dilated cardiomyopathy (33 idiopathic and 32 post ischemic etiology; NYHA II-III) were studied. We divided the patients into: Group A -patients with not-sustained ventricular arrhythmias-; and Group B -patients without arrhythmias-. A significant direct correlation between QTd calculated from 12-lead ECG and from ECG Holter was found in all patients. QTda/24h was not significantly different in the two groups (Gr.A 59.9+/-7.8 msec vs Gr.B 53.6+/ 8.4 msec p=ns) while QTde/24h was significantly higher in Group A (Gr.A 81.9+/ 5.9 msec vs Gr.B 44.5+/-6.8 msec; p<0.005). In post-ischemic etiology (32 pts; 17 with arrhythmias) the correlation between QTde/24h and ventricular arrhythmias was confirmed (Gr.A 81.4+/-7.8 msec vs Gr.B 42.6+/-6.2 msec p<0.002). CONCLUSIONS: ECG Holter recordings can evaluate QTd as well as the QTd on 12-lead ECG. An increased QTde/24h seems to be correlated with the occurence of ventricular arrhythmias in patients with dilated cardiomyopathy and can then be a useful tool to select patients at high risk for sudden death. PMID- 21977250 TI - Antihypertensive and cardiovascular effects of combined blockade of renin angiotensin system with ACE inhibitor and angiotensin II type 1 receptor blocker in hypertensive patients: A 24-week randomized controlled double-dummy trial. AB - BACKGROUND.: In this study the effects of 24 weeks losartan and ramipril treatment, both alone and in combination, on blood pressure and left ventricular mass (LVM) and function, have been evaluated in hypertensives. METHODS.: 57 hypertensives with stage 1 and 2 essential hypertension were included. After 4 weeks run in, a randomized double-blind, 3 arm, double dummy, independent trial was used. All patients were randomly allocated to 3 treatment arms consisting of losartan (50 mg/daily), ramipril (5 mg/daily), and combined (losartan 50 mg/ramipril 5 mg/daily) for 24 weeks. LVM, LVM/h(2.7) and other echocardiographic measurements, BUN, creatinine and clearance and potassium were determined after run in and 24 weeks. RESULTS.: All groups were comparable for gender, age, BMI, BP and LVM. The prevalence of baseline left ventricular hypertrophy (LVH) was not significantly different among 3 groups. At the end of treatment, a significant (p<0.05) reduction in SBP, DBP, MBP, LVM and LVM/h(2.7) were observed in all groups. The absolute and percent reduction in LVM/h(2.7) were significantly higher in combined than losartan or ramipril groups and also in hypertensives with LVH. No significant change in absolute and percent reduction of SBP, DBP and MBP were found. CONCLUSIONS.: These data indicate an additional cardioprotective effect of dual blockade of RAS in hypertensive patients with and without left ventricular hypertrophy. PMID- 21977251 TI - Intensive hyperglycemia control reduces postoperative infections after open heart surgery. AB - BACKGROUND: Diabetes mellitus increases the risk of infections in patients undergoing cardiac surgery. We hypothesized that intensive perioperative hyperglycemia control by intravenous insulin infusion reduces postoperative infections in all patients undergoing open heart surgical procedures. METHODS: Sixty diabetics patients who underwent CABG operation (Group 1) were compared with fifty-five patients who underwent other cardiac surgery (Group 2) between January 2004 and March 2005. A continuous infusion of insulin was used in all these patients. RESULTS: There were no 30-day mortalities in either group. There was no difference in the incidence of infections between the two groups: in Group 1, 3 (5%) patients were diagnosed to have postoperative infection (superficial sternal wound infections in 1 (1.66%) and lung infection in 2 (3.33%) patients); postoperative infection occurred in only 2 patients (3.63%) in Group 2, 1 superficial sternal wound infections (1.81%) and 1 lung infection (1.81%). CONCLUSIONS: Our analysis indicates that continuous intravenous insulin infusion improves outcome and reduces postoperative infections in patients undergoing CABG as well as those undergoing other cardiac surgery procedures. PMID- 21977252 TI - Microvascular obstruction after successful fibrinolytic therapy in acute myocardial infarction. Comparison of reteplase vs reteplase+abciximab: A cardiovascular magnetic resonance study. AB - BACKGROUND.: About one third of patients with TIMI 3 after reperfusion have evidence of microvascular obstruction (MO) which represents an independent predictor of myocardial wall rupture. This explains all efforts made to prevent MO. Magnetic resonance imaging (MRI) has proved to be particularly useful in detecting MO. The aim of this study was to evaluate with MRI if different fibrinolytic regimens in acute myocardial infarction display different effects on left ventricle (LV) volumes and ejection fraction (EF), as well as on myocardial infarct size (MIsz) and MO. METHODS.: Twenty male patients, mean age 58 years, affected by acute myocardial infarction, ten anterior and ten inferior, were treated with: full dose reteplase in ten, and half dose reteplase plus full dose abciximab (R+Abcx) in the other ten patients. In the fourth day after hospital admission, MRI STIR T2 images were used to quantify MIsz, while 2dflash cineloops were used after the injection of gadolinium, to quantify LV volumes, EF and to detect MO. RESULTS.: LV EF was higher in R+Abcx 51+/-10 than in reteplase 41+/ 8. MIsz was similar in both treatment groups: however a close relationship was present between MIsz and EF in the reteplase group indicating that the greater the MIsz the lower the EF. In R+Abcx this relationship was no longer present, suggesting a protective effect of the drug on microcirculation. In fact extensive MO was present in 25% of all cases, 80% of which in the reteplase group while only 20% in R+Abcx. CONCLUSION.: R+Abcx prevents MO: compared to traditional fibrinolytic therapy it allows better LV function and most likely improved long term survival. PMID- 21977254 TI - Sudden death prevention in heart failure: The case of CIBIS III. PMID- 21977253 TI - Takayasu's arteritis: A case report and a brief review of the literature. AB - Takayasu's arteritis primarily affects young women. The current case report focuses on a Caucasian middle-aged woman who complained of weakness, malaise, and fatigue for as many as 19 years. Delayed diagnosis and lack of specific treatment could explain the extent and the clinical severity of the disease at time of hospital admission. Angiography showed focal narrowings of the abdominal and thoracic aorta and occlusion of both the subclavian arteries, of the right coronary artery and severe stenosis of the first marginal obtuse. Takayasu's arteritis is not limited to women of Japanese origin but is present worldwide. Early diagnosis and treatment is warranted. Outcome appears to be favorable when the disease is quiescent. PMID- 21977255 TI - Discovering a new role for the atrial natriuretic peptide: A novel risk factor for cardiovascular diseases. AB - Atrial natriuretic peptide, a diuretic, natriuretic and vasorelaxant hormone, is also involved in the regulation of cardiovascular remodeling and it has been recently shown to be significantly associated with higher occurrence of cardiovascular diseases. In fact, high plasma ANP levels predict higher mortality rate for cardiovascular events. Moreover, ANP gene alterations are associated with higher risk of cardiovascular intermediate phenotypes, such as left ventricular hypertrophy, and of cardiovascular diseases, such as stroke and hypertension. Thus, the characterization of ANP plasma levels, and of ANP genotype for known mutations can be proposed as an informative component of the individual cardiovascular risk profile. PMID- 21977257 TI - AngioJet thrombectomy for the treatment of coronary artery aneurysm after failed thrombolysis in acute myocardial infarction. AB - Acute myocardial infarction (AMI) is caused by thrombus formation over a disrupted plaque occluding an epicardial coronary artery. Mechanical thrombectomy is effective in removing thrombus burden from native vessels and saphenous vein grafts. Here we report a case of an aneurysmatic dilatation of an infarct-related artery (IRA) referred to our Institute for rescue PCI, after failed fibrinolysis, successfully treated with only rheolytic thrombectomy (AngioJet, Possis Medical, Minneapolis, Minnesota, USA) without the need for adjunctive balloon or stent implantation. PMID- 21977256 TI - Myocardial infarction in major noncardiac surgery: Epidemiology, pathophysiology and prevention. AB - The number of subjects undergoing major noncardiac surgery who are at risk for perioperative myocardial infarction (MI) is growing worldwide.It has been estimated that 500,000 to 900,000 patients suffer major perioperative cardiovascular complications every year, with consequent heavy, long-term prognostic implications and costs.It is well known that perioperative MIs don't share the same pathophysiology as nonsurgical MIs but the relative role of the different, potential triggers has not been completely clarified.Many aspects of the perioperative management, including risk-stratification and prophylactic or postoperative interventions have also not been completely defined.Throughout recent years many resources have been invested to clarify these aspects and experts have developed indices and algorithm-based strategies to better assess the cardiac risk and to guide the perioperative management.The scope of the present review is to discuss the main aspects of perioperative MI in noncardiac surgery, with particular regard to epidemiology, pathophysiology, preoperative risk stratification, prophylaxis and therapy. PMID- 21977258 TI - Omega-3 polyunsaturated fatty acids: Their potential role in blood pressure prevention and management. AB - Omega-3 polyunsaturated fatty acids (PUFAs) from fish and fish oils appear to protect against coronary heart disease: their dietary intake is in fact inversely associated to cardiovascular disease morbidity/mortality in population studies. Recent evidence suggests that at least part of their heart protective effect is mediated by a relatively small but significant decrease in blood pressure level. In fact, omega-3 PUFAs exhibit wide-ranging biological actions that include regulating both vasomotor tone and renal sodium excretion, partly competing with omega-6 PUFAs for common metabolic enzymes and thereby decreasing the production of vasocostrincting rather than vasodilating and anti-inflammatory eicosanoids. PUFAs also reduce angiotensin-converting enzyme (ACE) activity, angiotensin II formation, TGF-beta expression, enhance eNO generation and activate the parasympathetic nervous system. The final result is improved vasodilation and arterial compliance of both small and large arteries. Preliminary clinical trials involving dyslipidemic patients, diabetics and elderly subjects, as well as normotensive and hypertensive subjects confirm this working hypothesis. Future research will clarify if PUFA supplementation could improve the antihypertensive action of specific blood pressure lowering drug classes and of statins. PMID- 21977259 TI - Effect of hypertrophy on left ventricular diastolic function in patients with hypertrophic cardiomyopathy. AB - BACKGROUND.: Hypertrophic cardiomyopathy (HCM) is characterized by asymmetric LV hypertrophy (LVH) and impairment in diastolic function. We assess the relationship between LVH and invasive indexes of diastolic function. METHODS.: 21 HCM patients underwent cardiac catheterization to assess pulmonary capillary wedge pressure, LV end-diastolic pressure (measured by microtip catheters), and LV volumes (calculated by simultaneous radionuclide angiography). We calculated from LV pressure the time constant of isovolumetric relaxation (tau, variable asymptote method, ms), and from LV pressure and volume the constant of chamber stiffness (k, ml(-1)). LVH was assessed by different indexes: maximal wall thickness, number of hypertrophied LV segments, LVH index, and Wigle's score. Results. Wigle's score was directly related to pulmonary capillary Wedge pressure (r=0.436, p=0.048), peak V wave of pulmonary capillary wedge pressure (r=0.503, p=0.024), LV end-diastolic pressure (r=0.643, p=0.002) and k (r=0.564, p=0.015). HCM patients were divided into 2 groups according to Wigle's score: 10 with mild or moderate LVH (< 8), and 11 with severe LVH (>= 8). HCM patients with severe LVH showed a higher pulmonary capillary Wedge pressure (15.1+/-7.2 vs 9.5+/-2.4, p=0.033), peak V wave of pulmonary capillary wedge pressure (20.7+/-4.6 vs 14.6+/ 4.9, p=0.011), LV end-diastolic pressure (23.9+/-10.9 vs 10.6+/-2.5, p=0.002), k (0.0465+/-0.032 vs 0.015+/-0.007, p=0.022) and LV outflow tract gradient (72+/-36 mmHg vs 29+/-30 mmHg, p=0.01).tau was similar in the two groups. Other indexes of LVH were not related to diastolic function. CONCLUSIONS.: Wigle's score is the only index of LVH that relates to invasive indices of diastolic function. PMID- 21977261 TI - Heart rate variability analysis in postural orthostatic tachycardia syndrome: a case report. AB - The authors present a case of 36 year old male patient with idiopathic postural orthostatic tachycardia syndrome (POTS) diagnosed during head-up tilt testing. Power spectral analysis of heart rate variability (HRV) during the tilt test revealed that the ratio of low and high frequency powers (LF/HF) increased with the onset of orthostatic intolerance. This analysis confirmed in our patient a strong activation in sympathetic tone. PMID- 21977260 TI - Endothelial damage due to air pollution. PMID- 21977263 TI - Improved graft patency rates and mid-term outcome of diabetic patients undergoing total arterial myocardial revascularization. AB - OBJECTIVES: Diabetes negatively affects the outcome of patients undergoing percutaneous transluminal coronary angioplasty (PTCA) or coronary surgery. However, data are lacking with respect to the impact of arterial revascularization in the diabetic population. METHODS: Between 1999 and 2003, 100 of 491 diabetics underwent coronary artery bypass graft surgery (CABG) with total arterial grafting (Group 1, G1); these patients were compared with 100 diabetics undergoing conventional CABG with saphenous veins (Group 2, G2), who were matched for Euroscore and other risk factors such as age, obesity, hypertension, left ventricular ejection fraction (LVEF), previous myocardial infarction and chronic obstructive pulmonary disease (COPD). RESULTS: Both groups had a similar number of diseased coronary vessels (G1=2.6 vs G2= 2.7) and received a similar degree of myocardial revascularization (grafted vessels: G1=2.2 vs G2=2.4). Early outcome was comparable between the groups in terms of ventilatory support (G1=10.8+/-6 vs G2=10.4+/-5 hours), intensive care unit (ICU) stay (G1=24+/-12 vs G2=25+/-14 hours) and major post-operative complications such as atrial fibrillation (G1=26% vs G2=28%), peri-operative myocardial infarction (G1=1% vs G2=2%)and prolonged ventilatory support (G1=6% vs G2=5%). Hospital mortality was 2% in G1 and 3% in G2. Angiography was performed at a mean follow-up of 34 months in 65.9% and 71.1% of hospital survivors of G1 and G2 respectively: patients of G1 showed a significantly higher patency rate (G1=96% vs G2=83.6%, p=0.02). Additionally, patients of G1 showed a significantly lower incidence of recurrent myocardial ischemia (G1=7 pts. vs G2=18 pts., p=0.03), late myocardial infarction (G1=2 pts. vs G2=10 pts., p=0.03) and need for coronary reintervention (G1=1 pt. vs G2=12 pts, p=0.004). CONCLUSIONS: Total arterial grafting in diabetic patients significantly improved the benefits of coronary surgery providing at mid term a higher graft patency rate with a lower incidence of cardiac related events. PMID- 21977262 TI - The immune system in atherosclerosis and in acute myocardial infarction. PMID- 21977264 TI - Antiatherogenic effects of n-3 fatty acids - evidence and mechanisms. AB - N-3 (omega-3) (polyunsaturated) fatty acids are thought to display a variety of beneficial effects for human health. Clues to the occurrence of cardiovascular protective effects have been, however, the spur for the first biomedical interest in these compounds, and are the best documented. Historically, the epidemiologic association between dietary consumption of n-3 fatty acids and cardiovascular protection was first suggested by Bang and Dyerberg, who identified the high consumption of fish, and therefore, of fish oil-derived n-3 fatty acids, as the likely explanation for the strikingly low rate of coronary heart disease events reported in the Inuit population. Since their initial reports, research has proceeded in parallel to provide further evidence for their cardioprotection and to understand underlying mechanisms. Decreased atherogenesis is currently thought to be a part of the cardiovascular protection by n-3 fatty acids. This article summarizes the evidence for such a claim and the mechanisms putatively involved. PMID- 21977265 TI - Cholesterol crystal embolism (atheroembolism). AB - Cholesterol crystal embolism, known as atheroembolic disease, is caused by showers of cholesterol crystals from an atherosclerotic plaque that occludes small arteries. Embolization can occur spontaneously or as an iatrogenic complication from an invasive vascular procedure (angiography or vascular surgery) and after anticoagulant therapy. The atheroembolism can give rise to different degrees of renal impairment. Some patients show a moderate loss of renal function, others severe renal failure requiring dialysis. Renal outcome can be variable: some patients deteriorate or remain on dialysis, some improve and some remain with chronic renal impairment. Clinically, three types of atheroembolic renal disease have been described: acute, subacute or chronic. More frequently a progressive loss of renal function occurs over weeks. Atheroembolization can involve the skin, gastrointestinal system and central nervous system. The diagnosis is difficult and controversial for the protean extrarenal manifestations. In the past, the diagnosis was often made post-mortem. In the last 10 yrs, awareness of atheroembolic renal disease has improved. The correct diagnosis requires the clinician to be alert. The typical patient is a white male aged >60 yrs with a history of hypertension, smoking and arterial disease. The presence of a classic triad (precipitating event, renal failure and peripheral cholesterol crystal embolization) suggests the diagnosis. This can be confirmed by a biopsy of the target organs. A specific treatment is lacking; however, it is an important diagnosis to make because an aggressive therapeutic approach can be associated with a more favorable clinical outcome. PMID- 21977266 TI - Atrial flutter: from ECG to electroanatomical 3D mapping. AB - Atrial flutter is a common arrhythmia that may cause significant symptoms, including palpitations, dyspnea, chest pain and even syncope. Frequently it's possible to diagnose atrial flutter with a 12-lead surface ECG, looking for distinctive waves in leads II, III, aVF, aVL, V1,V2. Puech and Waldo developed the first classification of atrial flutter in the 1970s. These authors divided the arrhythmia into type I and type II. Therefore, in 2001 the European Society of Cardiology and the North American Society of Pacing and Electrophysiology developed a new classification of atrial flutter, based not only on the ECG, but also on the electrophysiological mechanism. New developments in endocardial mapping, including the electroanatomical 3D mapping system, have greatly expanded our understanding of the mechanism of arrhythmias. More recently, Scheinman et al, provided an updated classification and nomenclature. The terms like common, uncommon, typical, reverse typical or atypical flutter are abandoned because they may generate confusion. The authors worked out a new terminology, which differentiates atrial flutter only on the basis of electrophysiological mechanism. PMID- 21977267 TI - Diagnostic value of the head-up tilt test and the R-test in patients with syncope. AB - The diagnostic value of the head-up tilt test (HUTT) in discovering vasovagal syndrome depends on the pre-test probability. An accurate anamnesis and clinical examination screens the patients indicated for the HUTT. In patients with unexplained syncope, the R-test is an alternative procedure to discover its cause. In our study, we evaluated the diagnostic significance of the HUTT in a group of 211 patients and of the R-test in a subgroup of 45 patients with negative HUTT results and with negative traditional Holter ECG monitoring (24 hr). PMID- 21977268 TI - Non-compaction of the ventricular myocardium. AB - Non-compaction of the left ventricle (LVNC) is a disorder of endomyocardial morphogenesis that results in multiple trabeculations in the left ventricular (LV) myocardium. This rare disorder is characterized by an excessively prominent trabecular meshwork and deep intratrabecular recesses. This idiopathic cardiomyopathy is characterized by an altered structure of the myocardial wall as a result of intrauterine arrest of compaction of the myocardial fibers in the absence of any coexisting congenital lesion. It can be associated with neuromuscular disorders and can co-exist with other cardiac malformations, and it is accompanied by depressed ventricular function, systemic embolism and ventricular arrhythmia. Echocardiography is the method of choice for diagnosing LVNC, but the correct diagnosis is often missed or delayed due to a lack of knowledge concerning this uncommon disease and its similarity to other diseases of the myocardium and endocardium. There is a two-layered structure of the myocardial wall consisting of a thin compacted epicardial layer and a thick non compacted endocardial layer with prominent trabeculations and deep recesses. PMID- 21977269 TI - Anemia and heart failure: a cause of progression or only a consequence? AB - Anemia is one of the most frequent co-morbidities in the patients with heart failure. Its prevalence increases from 4-7% in the subjects with asymptomatic left ventricular dysfunction to >30% in the patients with severe heart failure. Renal insufficiency, activation of inflammatory mediators, and treatment with renin-angiotensin antagonists seem to be its main determinants. The results of many studies agree in showing that anemia is a powerful independent determinant of survival in patients with heart failure. However, the mechanisms of this relation are still incompletely understood. Moreover a favourable effect on prognosis of the correction of anemia has not been shown, yet, and also controlled studies assessing its effects on exercise tolerance have yielded controversial results. PMID- 21977270 TI - The combination of Ezetimibe and Statin: a new treatment for hypercholesterolemia. AB - The combination of Simvastatin and Ezetimibe allows dual inhibition of both cholesterol production and absorption. This treatment approach allows achieving same low serum cholesterol levels with the administration of much lower doses of statins. This should reduce side effects, compared to statin only therapy, enabling more patients to achieve their LDL cholesterol treatment goals. With ezetimibe/simvastatin therapy, reductions of about 60% from baseline in LDL cholesterol have been shown. Concomitant improvement in other lipid fractions have also been demonstrated. The ezetimibe/simvastatin combination has been well tolerated, with a safety profile similar to that of statin therapy. This article will review clinical experience with ezetimibe/simvastatin combination, commenting upon its place and potential value in the prevention of cardiovascular disease. PMID- 21977271 TI - Nitric oxide and cardiovascular risk factors. PMID- 21977272 TI - Endocannabinoids and cardiovascular prevention: real progress? AB - The prevalence of obesity continues to increase and represents one of the principal causes of cardiovascular morbidity and mortality. After the discovery of a specific receptor of the psychoactive principle of marijuana, the cannabinoid receptors and their endogenous ligands, several studies have demonstrated the role of this system in the control of food intake and energy balance and its overactivity in obesity. Recent studies with the CB1 receptor antagonist rimonabant have demonstrated favorable effects such as a reduction in body weight and waist circumference and an improvement in metabolic factors (cholesterol, triglycerides, glycemia etc). Therefore, the antagonism of the endocannabinoid (EC) system, if recent data can be confirmed, could be a new treatment target for high risk overweight or obese patients. Obesity is a growing problem that has epidemic proportions worldwide and is associated with an increased risk of premature death (1-3). Individuals with a central deposition of fats have elevated cardiovascular morbidity and mortality (including stroke, heart failure and myocardial infarction) and, because of a growing prevalence not only in adults but also in adolescents, it was reclassified in AHA guidelines as a "major modifiable risk factor" for coronary heart disease (4, 5). Although first choice therapy in obesity is based on correcting lifestyle (diet and physical activity) in patients with abdominal obesity and high cardiovascular risk and diabetes, often it is necessary to use drugs which reduce the risks. The EC system represents a new target for weight control and the improvement of lipid and glycemic metabolism (6, 7). PMID- 21977273 TI - Three-dimensional echocardiography in valve disease. AB - This review covers the role of three-dimensional (3D) echocardiography in the diagnosis of heart valve disease. Several factors have contributed to the evolution of this technique, which is currently a simple and routine method: rapid evolution in probe and computer technologies, demonstration that 3D data sets allowed more complete and accurate evaluation of cardiac structures, emerging clinical experience indicating the strong potential particularly in valve diseases, volume and function of the two ventricle measurements and several other fields. This report will review current and future applications of 3D echocardiography in mitral, aortic and tricuspid valve diseases underlying both qualitative (morphologic) and quantitative advantages of this technique. PMID- 21977274 TI - The study of left ventricular diastolic function by Doppler echocardiography: the essential for the clinician. AB - An abnormal diastolic function of left ventricle represents the main pathophysiological mechanism responsible for different clinical states such as restrictive cardiomyopathy, infiltrative myocardial disease and, specially, diastolic heart failure (also called heart failure with preserved systolic function), which is present in a large number of patients with a clinical picture of pulmonary congestion.Although the invasive approach, through cardiac catheterization allowing the direct measurement of left ventricular filling pressure, myocardial relaxation and compliance, is considered the gold standard for the identification of diastolic dysfunction, several noninvasive methods have been proposed for the study of left ventricular diastolic function.Doppler echocardiography represents an excellent noninvasive technique to fully characterize the diastolic function in health and disease. PMID- 21977275 TI - Heart rate turbulence and variability in patients with ventricular arrhythmias. AB - BACKGROUND: To evaluate the changes in autonomic neural control mechanisms before malignant ventricular arrhythmias, we measured heart rate variability (HRV) and heart rate turbulence (HRT) in patients with ventricular tachycardia or fibrillation (Group I; n=6), non sustained ventricular tachycardia (Group II; n=32), frequent premature ventricular beats (Group III; n=26) and with ICD implantation (Group IV; n=11). METHODS: Time domain parameters of HRV and turbulence onset (TO) and slope (TS) were calculated on 24 hour Holter recordings. Normal values were: SDNN > 70 msec for HRV, TO <0% and TS >2.5 msec/RR-I for HRT. RESULTS: Whereas SDNN was within normal range and similar in all study groups, HRT parameters were significantly different in patients who experienced VT/VF during Holter recording. Abnormal TO and/or TS were present in 100% of Group I patients and only in about 50% of Group II and IV. On the contrary, normal HRT parameters were present in 40-70% of Group II, III and IV patients and none of Group I. CONCLUSIONS: These data suggest that HRT analysis is more suitable than HRV to detect those transient alterations in autonomic control mechanisms that are likely to play a major trigger role in the genesis of malignant cardiac arrhythmias. PMID- 21977276 TI - Ventricular arrhythmias in competitive athletes: risk stratification with T-wave alternans. AB - INTRODUCTION: Aim of our study is to evaluate the role of TWA to stratify the risk of sudden cardiac death in athletes (Ath) with complex ventricular arrhythmias (VA), and to document a possible correlation between TWA and electrophysiological testing (EES) results. METHODS: We studied 43 Ath with VA (31 M, mean age 34 +/- 12 years). In all cases a cardiological evaluation was performed, including TWA and EES. The patients were evaluated during a follow-up of 25 +/- 22 months. The end-point was the occurrence of sudden death or malignant ventricular tachyarrhythmias (VT). RESULTS: TWA was negative in 28 Ath (65%), positive in 8 (19%) and indeterminate in 7 (16%). All subjects with negative TWA did not show induction of VT at EES, with significant correlation between negative TWA and negative EES (p<0.001). All Ath with positive TWA also had VT induced by a EES, but without significant correlation between positive TWA and positive EES. In 2 Ath with undetermined TWA (29%) VT were induced at EES. Our data did not show significant correlation between indeterminate TWA and positive or negative EES. However, logistic regression analysis showed significant correlation between abnormal TWA test (positive or indeterminate) and inducibility of VT at EES (p<0.001). During follow-up we observed a significant difference in end-point occurrence between Ath with negative or positive TWA and between Ath with negative or positive EES. CONCLUSION: TWA confirm its role as a simple and non-invasive test, and it seems useful for prognostic stratification of Ath with VA. PMID- 21977277 TI - HAS-1 genetic polymorphism in sporadic abdominal aortic aneurysm. AB - The hyaluronan synthase 1 (HAS-1) gene encodes a plasma membrane protein that synthesizes hyaluronan (HA), an extracellular matrix molecule. Accumulating evidence emphasizes the relevance of HA metabolism in an increasing number of processes of clinical interest, including abdominal aortic aneurysm (AAA). The existence of aberrant splicing variants of the HAS-1 gene could partly explain the altered extracellular matrix architecture and influence various biological functions, resulting in progressive arterial wall failure in the development of AAA. In the present study, we assessed the hypothesis that HAS-1 genetic 833A/G polymorphism could be associated with the risk of AAA by performing a case control association study, involving AAA patients and healthy matched donors. PMID- 21977278 TI - Cardiovascular safety of celecoxib in acute myocardial infarction patients: a nested case-control study. AB - The objective was to measure the impact of exposure to coxibs and non-steroidal antiinflammatory drugs (NSAID) on morbidity and mortality in older patients with acute myocardial infarction (AMI). A nested case-control study was carried out using an exhaustive population-based cohort of patients aged 66 years and older living in Quebec (Canada) who survived a hospitalization for AMI (ICD-9 410) between 1999 and 2002. The main variables were all-cause and cardiovascular (CV) death, subsequent hospital admission for AMI, and a composite end-point including recurrent AMI or CV death. Conditional logistic regressions were used to estimate the risk of mortality and morbidity. A total of 19,823 patients aged 66 years and older survived hospitalization for AMI in the province of Quebec between 1999 and 2002. After controlling for covariables, the risk of subsequent AMI and the risk of composite end-point were increased by the use of rofecoxib. The risk of subsequent AMI was particularly high for new rofecoxib users (HR 2.47, 95% CI 1.57-3.89). No increased risk was observed for celecoxib users. No increased risk of CV death was observed for patients exposed to coxibs or NSAIDs. Patients newly exposed to NSAIDs were at an increased risk of death (HR 2.22, 95% CI 1.30-3.77) and of composite end-point (HR 2.28, 95% CI 1.35-3.84). Users of rofecoxib and NSAIDs, but not celecoxib, were at an increased risk of recurrent AMI and of composite end-point. Surprisingly, no increased risk of CV death was observed. Further studies are needed to better understand these apparently contradictory results. PMID- 21977279 TI - Coronary artery disease, left ventricular hypertrophy and diastolic dysfunction are associated with stroke in patients affected by persistent non-valvular atrial fibrillation: a case-control study. AB - Persistent non-valvular atrial fibrillation (NVAF) is associated with an increased risk of cardiovascular events such as stroke, and its rate is expected to rise because of the ageing population. The absolute rate of stroke depends on age and comorbidity. Risk stratification for stroke in patients with NVAF derives from populations enrolled in randomized clinical trials. However, participants in clinical trials are often not representative of the general population. Many stroke risk stratification scores have been used, but they do not include transthoracic echocardiogram (TTE), pulsate wave Doppler (PWD) and tissue Doppler imaging (TDI), simple and non- invasive diagnostic tools. The role of TTE, PWD and TDI findings has not been previously determined. Our study goal was to determine the association between TTE and PWD findings and stroke prevalence in a population of NVAF prone outpatients.PATIENTS WERE DIVIDED INTO TWO GROUPS: P for stroke prone and F for stroke free. There were no statistically significant differences between the two groups concerning cardiovascular risk factors, age (p=0.2), sex (p=0.2), smoking (p=0.3), diabetes (p=0.1) and hypercholesterolemia (p=0.2); hypertension was statistically significant (p<0.001). There were statistically significant differences concerning coronary artery disease, previous acute myocardial infarction (AMI) (p<0.05) and non- AMI coronaropathy (p<0.04), a higher rate being in the P group. Concerning echo-Doppler findings, a higher statistically significant rate of left ventricular hypertrophy (LVH) (p<0.05) and left ventricular diastolic dysfunction (p<0.001) was found in the P group and dilated left atrium (p<0.04) in the F group, the difference was not significant for mitral regurgitation (p=0.7). Stroke prone NVAF patients have a higher rate of hypertension, coronary artery disease, with and without AMI, LVH and left ventricular diastolic dysfunction, but not left atrial dilatation. M-B mode echocardiography and PWD examination help to identify high-risk stroke patients among NVAF subjects; therefore, they may help in the selection of appropriate therapy for each patient. PMID- 21977280 TI - Atrial and ventricular function in thalassemic patients with supra-ventricular arrhythmias. AB - The aims of this study were to evaluate through Color Doppler Myocardial Imaging (CDMI) echocardiography if atrial or ventricular myocardial alterations could be detectable in patients with thalassemia major (THAL) and if these alterations could be considered as predictive elements for supra-ventricular arrhythmic events. Twenty-three patients with THAL underwent clinical and electrocardiographic evaluation; patients were grouped in THAL1 (9 with supra ventricular arrhythmias) and THAL2 (14 without arrhythmias); 12 healthy subjects were considered as control group (C). We examined through conventional 2D Color Doppler echocardiography some morphological and functional parameters regarding left ventricular (LV) systolic and diastolic function, and through CDMI the velocities at mitral annulus level, the regional LV and left atrial (LA) strain and strain rate. All THAL patients had LV dimension (p<0.05), LA area (p<0.01) and E/Em ratio (p<0.001) to be significantly higher than controls. The mitral annulus longitudinal velocities were significantly lower in THAL1 than in THAL2 (p<0.001); the E/Em ratio was higher in THAL1 than THAL2 (p<0.001). The THAL1 showed a lower systolic strain rate of atrial wall than THAL2 and C (p<0.05). The multiple regression highlighted a significantly inverse correlation among E/Em and atrial strain (p<0.02). CDMI showed both THAL subgroups had subtle systolic and diastolic left ventricular myocardial alterations, which could represent the onset of developing "iron cardiomyopathy" and are related to supra-ventricular arrhythmia. Monitoring these parameters in the THAL patients could contribute to decisions about follow-up and therapy. PMID- 21977281 TI - Plasma matrix metalloproteinases in neonates having surgery for congenital heart disease. AB - During cardiopulmonary-bypass matrix-metalloproteinases released may contribute to ventricular dysfunction. This study was to determine plasma matrix metalloproteinases in neonates after cardiopulmonary-bypass and their relation to post-operative course. A prospective observational study included 18 neonates having cardiac surgery. Plasma matrix-metalloproteinases-2 and 9 activities were measured by gelatin-zymography pre-operatively, on starting cardiopulmonarybypass, 7-8 min after aortic cross-clamp release, and 1h, 4h, 24h, and 3d after cardiopulmonary-bypass. Plasma concentrations of their tissue inhibitors 1 and 2 were determined by enzyme-linked immunosorbent assay. Cardiac function was assessed by serial echocardiography. Paired t-tests and Wilcoxon tests were used to assess temporal changes, and linear correlation with simultaneous clinical and cardiac function parameters were assessed using Pearson's product-moment correlation coefficient. Plasma matrix metalloproteinases activities and their tissue inhibitor concentrations decreased during cardiopulmonary-bypass. Matrix-metalloproteinase-2 plasma activity increased progressively starting 1h after cardiopulmonarybypass and returned to pre-operative levels at 24h. Matrix-metalloproteinase-9 plasma activity increased significantly after release of aortic cross-clamp, peaked 7-8min later, and returned to baseline at 24h. Plasma tissueinhibitor 1 and 2 concentrations increased 1h after cardiopulmonary-bypass. Cardiac function improved from 4h to 3d after surgery (p<0.05). There was no evidence of significant correlations between matrix-metalloproteinases or their inhibitors and cardiac function, inotrope scores, organ dysfunction scores, ventilation days, or hospital days. The temporal profile of plasma matrix-metalloproteinases and their inhibitors after cardiopulmonary-bypass in neonates are similar to adults. In neonates, further study should determine whether circulating matrix-metalloproteinases are useful biomarkers of disease activity locally within the myocardium, and hence of clinical outcomes. PMID- 21977282 TI - Capnocytophaga canimorsus endocarditis with root abscess in a patient with a bicuspid aortic valve. PMID- 21977283 TI - Role of the IRS-1 and/or -2 in the pathogenesis of insulin resistance in Dahl salt-sensitive (S) rats. AB - Insulin resistance is a common finding in hypertensive humans and animal models. The Dahl salt-sensitive (S) rat is an ideal model of genetically predetermined insulin resistance and salt-sensitive hypertension. Along the insulin signaling pathway, the insulin receptor substrates 1 and 2 (IRS-1 and -2) are important mediators of insulin signaling. IRS-1 and/or IRS-2 genetic variant(s) and/or enhanced serine phosphorylation correlate with insulin resistance. The present commentary was designed to highlight the significance of IRS-1 and/or -2 in the pathogenesis of insulin resistance. An emphasis will be given to the putative role of IRS-1 and/or -2 genetic variant(s) and serine phosphorylation in precipitating insulin resistance. PMID- 21977284 TI - Effects of N-acetyl-cysteine on endothelial function and inflammation in patients with type 2 diabetes mellitus. AB - Endothelial dysfunction has been associated with premature vascular disease. There is increasing data that N-acetyl-cysteine (NAC) may prevent or improve endothelial dysfunction. The aim of this study was to assess the effects of NAC on endothelial function in patients with type 2 diabetes mellitus, a population at high risk for endothelial dysfunction. Twenty-four patients with diabetes mellitus were assigned randomly to initial therapy with either 900 mg NAC or placebo twice daily in a double-blind, cross-over study design. Flowmediated vasodilation (FMD) of the brachial artery was assessed at baseline, after four weeks of therapy, after a four-week wash-out period, and after another four weeks on the opposite treatment. Plasma and red blood cell glutathione levels and high sensitivity C-reactive protein (CRP) were measured at all four visits. At baseline, FMD was moderately impaired (3.7+/-2.9%). There was no significant change in FMD after four weeks of NAC therapy as compared to placebo (0.1+/-3.6% vs. 1.2+/-4.2%). Similarly, there was no significant change in glutathione levels. However, median CRP decreased from 2.35 to 2.14 mg/L during NAC therapy (p=0.04), while it increased from 2.24 to 2.65 mg/L with placebo. No side effects were noted during the treatment period. In this double-blind, randomized cross over study, four weeks of oral NAC therapy failed to improve endothelial dysfunction in patients with diabetes mellitus. However, NAC therapy decreased CRP levels, suggesting that this compound may have some efficacy in reducing systemic inflammation. PMID- 21977285 TI - Effect of left ventricular hypertrophy on long-term survival of patients with coronary artery disease following percutaneous coronary intervention. AB - The impact of left ventricular hypertrophy (LVH) on survival among patients with established coronary artery disease (CAD) is not well understood. We sought to evaluate the effect of LVH on the survival of patients with CAD following percutaneous coronary intervention (PCI). Three hospitals in New York City contributed prospectively defined data on 4284 consecutive patients undergoing PCI. Allcause mortality at a mean follow-up of three years was the primary endpoint. LVH was present in 383 patients (8.9%). LVH patients had a greater prevalence of hypertension (88% vs. 68%, p<0.001), vascular disease (21% vs. 6.6%, p=0.001), and prior heart failure (10% vs. 5.5%, p<0.001). LVH patients presented less often with one-vessel disease (38% vs. 50%, p=0.040) and more often with two- (34% vs. 29%, p=0.014) or three-vessel (22% vs. 18%, p=0.044) disease. Ejection fractions and angiographic success were similar in both groups. In-hospital mortality did not differ between groups. At three-year follow-up, the survival rate for patients with LVH was 86% vs. 91% in patients without LVH (log rank p=0.001). However, after adjustment for differences in baseline characteristics using Cox proportional hazards analysis, LVH was found not to be an independent predictor of mortality (hazard ratio, 0.93; 95% confidence interval, 0.68-1.28; p=0.67). We conclude that LVH at the time of PCI is not independently associated with an increase in the hazard of death at three years. PMID- 21977286 TI - Mathematical modeling and experimental testing of three bioreactor configurations based on windkessel models. AB - This paper presents an experimental study of three bioreactor configurations. The bioreactor is intended to be used for the development of tissue-engineered heart valve substitutes. Therefore it must be able to reproduce physiological flow and pressure waveforms accurately. A detailed analysis of three bioreactor arrangements is presented using mathematical models based on the windkessel (WK) approach. First, a review of the many applications of this approach in medical studies enhances its fundamental nature and its usefulness. Then the models are developed with reference to the actual components of the bioreactor. This study emphasizes different conflicting issues arising in the design process of a bioreactor for biomedical purposes, where an optimization process is essential to reach a compromise satisfying all conditions. Two important aspects are the need for a simple system providing ease of use and long-term sterility, opposed to the need for an advanced (thus more complex) architecture capable of a more accurate reproduction of the physiological environment. Three classic WK architectures are analyzed, and experimental results enhance the advantages and limitations of each one. PMID- 21977287 TI - The association of microalbuminuria with mortality in patients with acute myocardial infarction. A ten-year follow-up study. AB - Our study evaluates the long-term effect of microalbuminuria on mortality among patients with acute myocardial infarction. We followed 151 patients from 1996 to 2007 to investigate if microalbuminuria is a risk factor in coronary heart disease. All patients admitted with acute myocardial infarction in 1996 were included. At baseline, we recorded urinary albumin/creatinine concentration ratio, body mass index, blood pressure, left ventricle ejection fraction by echocardiography, smoking status, medication, diabetes, age, and gender. Deaths were traced in 2007 by means of the Danish Personal Identification Register. Microalbuminuria, defined as a urinary albumin/creatinine concentration ratio above 0.65 mg/mmoL, occurred in 50% of the patients and was associated with increased all-cause mortality. Thus, 68% of the patients with microalbuminuria versus 48% of the patients without microalbuminuria had died during the 10 years of follow-up (P=0.04). The crude hazard ratio for death associated with microalbuminuria was 1.78 (CI: 1.18-2.68) (P=0.006), whereas the gender- and age adjusted hazard ratio was 1.71 (CI: 1.03-2.83) (P=0.04). We concluded that microalbuminuria in hospitalized patients with acute myocardial infarction is prognostic for increased long-term mortality. We recommend measurement of microalbuminuria to be included as a baseline risk factor in patients with acute myocardial infarction and in future trials in patients with coronary heart disease. PMID- 21977288 TI - Cyclic mechanical strain causes cAMP-response element binding protein activation by different pathways in cardiac fibroblasts. AB - The transcription factor cAMP-response element binding protein (CREB) mediates the mechanical strain-induced gene expression in the heart. This study investigated which signaling pathways are involved in the straininduced CREB activation using cultured ventricular fibroblasts from adult rat hearts. CREB phosphorylation was analyzed by immunocytochemistry and ELISA. Cyclic mechanical strain (1 Hz and 5% elongation) for 15 min induced CREB phosphorylation in all CREB-positive fibroblasts. Several signaling transduction pathways can contribute to strain-induced CREB activation. The inhibition of PKA, PKC, MEK, p38-MAPK or PI3-kinase partially reduced the strain-induced CREB phosphorylation. Activation of PKA by forskolin or PKC by PMA resulted in a level of CREB phosphorylation comparable to the reduced level of the strain-induced CREB phosphorylation in the presence of PKA or PKC inhibitors. Signaling pathways involving PKC, MEK, p38 MAPK or PI3-kinase seem to converge during strain-induced CREB activation. PKA interacted additively with the investigated signaling pathways. The strain induced c-Fos expression can be reduced by PKC inhibition but not by PKA inhibition. Our results suggest that the complete strain-induced CREB phosphorylation involves several signaling pathways that have a synergistic effect. The influence on gene expression is dependent on the level and the time of CREB stimulation. These wide-ranging possibilities of CREB activation provide a graduated control system. PMID- 21977289 TI - Predictors of appropriate therapy in patients with implantable cardioverter defibrillator for primary prevention of sudden cardiac death. AB - The purpose of this study was to evaluate predictors of appropriate therapy in patients with implantable cardioverter-defibrillators (ICD) for primary prevention of sudden cardiac death. A retrospective cohort of 321 patients with systolic heart failure undergoing ICD placement for primary prevention of sudden cardiac death was queried with a mean follow-up period of 2.6 years. Appropriate ICD therapy was defined as therapy delivered for termination of a ventricular tachyarrhythmia. Appropriate ICD therapy was delivered in 142 (44%) of the patients. In a multivariate model, body mass index >=28.8 kg/m(2), chronic kidney disease, left ventricular ejection fraction <=20% and metabolic syndrome were found to be independent predictors of appropriate ICD therapy. Appropriate ICD therapy was associated with higher cardiovascular mortality. These findings show the importance of identification of risk factors, especially metabolic syndrome, in patients following ICD implantation as aggressive treatment of these co morbidities may decrease appropriate ICD therapy and cardiovascular mortality. PMID- 21977290 TI - Lipid rescue for bupivacaine toxicity during cardiovascular procedures. PMID- 21977291 TI - Real-time three dimensional transesophageal echocardiography: technical aspects and clinical applications. AB - Real-time three-dimensional transesophageal echocardiography (RT3DTEE) is now commonly used in daily clinical practice. The transesophageal, compared to the transthoracic approach, allows the visualization of the whole spectrum of the mitral valve apparatus and the posterior cardiac structures. Moreover, images obtained by RT 3D TEE provide a unique and complete visualization of the mitral valve prosthetic elements. Indeed, the possibility to visualize guidewires and catheters in cardiac chambers and their relationship with cardiac structures during percutaneous transcatheter procedures reduces the time of radiation exposure and simplifies the approach becoming the reference method for monitoring. This review aims to underline the potential clinical applications and the advantages of RT3DTEE compared to other methods. PMID- 21977292 TI - Carbamazepine alone and in combination with doxycycline attenuates isoproterenol induced cardiac hypertrophy. AB - beta-adrenergic signaling is involved in the development of cardiac hypertrophy (CH), justifying the use of beta-blockers as a therapy to minimize and postpone the consequences of this disease. Evidence suggests that adenylate cyclase, a downstream effector of the beta-adrenergic pathway, might be a therapeutic target. We examined the effects of the anti-epileptic drug carbamazepine (CBZ), an inhibitor of adenylate cyclase. In a murine cardiac hypertrophy model, carbamazepine significantly attenuates isoproteronol (ISO)-induced cardiac hypertrophy. Carbamazepine also has an effect in transverse aortic banding induced cardiac hypertrophy (TAB) (P=0.07). When carbamazepine was given in combination with the antibiotic doxycycline (DOX), which inhibits matrix metalloproteinases (MMPs), therapeutic outcome measured by heart weight-to-body weight and heart weight-to-tibia length ratios was improved compared to either drug alone. Additionally, the combination therapy resulted in an increase in the survival rate over a 56-day period compared to that of untreated mice with cardiac hypertrophy or either drug used alone. Moreover, in support of a role for carbamaze -pine as a beta-adrenergic antagonist via cAMP inhibition, a lower heart rate and a lower level of the activated phosphorylated form of the cAMP Response Element-Binding (CREB) were observed in heart extracts from mice treated with carbamazepine. Gene expression analysis identified 19 genes whose expression is significantly altered in treated animals and might be responsible for the added benefit provided by the combination therapy. These results suggest that carbamazepine acts as a beta-adrenergic antagonist. Carbamazepine and doxycycline are approved by the US Food and Drug Administration (FDA) as drugs that might complement medications for cardiac hypertrophy or serve as an alternative therapy to traditional beta-blockers. Furthermore, these agents reproducibly impact the expression of genes that may serve as additional therapeutic targets in the management of cardiac hypertrophy. PMID- 21977293 TI - Initial experience using contrast enhanced real-time three-dimensional exercise stress echocardiography in a low-risk population. AB - Although emerging data support the utility of real-time three-dimensional echocardiography (RT3DE) during dobutamine stress testing, the feasibility of performing contrast enhanced RT3DE during exercise treadmill stress has not been explored. Two-dimensional (2D) and three-dimensional (3D) acquisition were performed in 39 patients at rest and peak exercise. Contrast was used in 29 patients (74%). Reconstruction was performed manually by generating short axis cut planes at the base, mid-ventricle and apex, and automatically by generating 9 short axis slices. Three-dimensional acquisition was feasible during rest and stress regardless of the use of contrast. Time to acquire stress images was reduced using 3D (35.2+/-17.9 s) as compared to 2D acquisition (51.6+/-14.7 s; P<0.05). Using a 17-segment model, of all 663 segments, 588 resting (88.6%) and 563 stress segments (84.9%) were adequately visualized using manually reconstructed 3D data, compared with 618 resting (93.2%) and 606 stress segments (91.4%) using 2D data (P rest=0.06; P stress=0.07). We concluded that contrast enhanced RT3DE is feasible during treadmill stress echocardiography. PMID- 21977294 TI - Cardiovascular research: data dispersion issues. AB - Biological processes are full of variations and so are responses to therapy as measured in clinical research. Estimators of clinical efficacy are, therefore, usually reported with a measure of uncertainty, otherwise called dispersion. This study aimed to review both the flaws of data reports without measure of dispersion and those with over-dispersion.EXAMPLES OF ESTIMATORS COMMONLY REPORTED WITHOUT A MEASURE OF DISPERSION INCLUDE: number needed to treat;reproducibility of quantitative diagnostic tests;sensitivity/specificity;Markov predictors;risk profiles predicted from multiple logistic models.Data with large differences between response magnitudes can be assessed for over-dispersion by goodness of fit tests. The chi(2) goodness of fit test allows adjustment for over-dispersion.For most clinical estimators, the calculation of standard errors or confidence intervals is possible. Sometimes, the choice is deliberately made not to use the data fully, but to skip the standard errors and to use the summary measures only. The problem with this approach is that it may suggest inflated results. We recommend that analytical methods in clinical research should always attempt to include a measure of dispersion in the data. When large differences exist in the data, the presence of over-dispersion should be assessed and appropriate adjustments made. PMID- 21977295 TI - Detection of severe left anterior descending coronary artery stenosis by transthoracic evaluation of resting coronary flow velocity dynamics. AB - In the presence of severe stenosis, coronary artery flow may be reduced at rest. Recent advances in echocardiography have made non-invasive sampling of velocities in the left anterior descending coronary artery (LAD) possible. The aim of our study was to evaluate feasibility and capability of transthoracic Doppler to detect severe stenosis of the LAD. The study population consisted of 42 subjects with suspected coronary artery disease scheduled for coronary angiography. All had complete transthoracic echocardiography and Doppler sampling of LAD velocities. Quantitative coronary angiography was performed within 24 hours of the echocardiogram. Correlations between LAD velocity profile, measurements and calculations, and the angiographic results were performed. Six subjects had LAD occlusion, 10 had severe (>80% diameter) LAD stenosis, and 26 had normal or non occlusive LAD disease. In all six subjects with LAD occlusion, distal LAD velocities were not detectable, while in the other 36 subjects, LAD velocities were recorded indicating the vessels were patent. In the 10 subjects with severe LAD stenosis, the diastolic/systolic velocity ratio was <1.5, while in those with non-significant LAD disease, the diastolic/systolic velocity ratio was >1.5 (P<0.005). Diastolic LAD flow was 21.8+/-13 mL/min in the presence of severe stenosis as compared to 48.5+/-20 mL/min in subjects without severe stenosis (P<0.0013). LAD velocities had high sensitivity and specificity for the prediction of severe angiographic stenosis. Thus transthoracic Doppler measurement of LAD velocities is feasible and can predict the presence of severe LAD stenosis or occlusion. PMID- 21977296 TI - Framingham risk prediction equations for incidence of cardiovascular disease using detailed measures for smoking. AB - Current prediction models for risk of cardiovascular disease (CVD) incidence incorporate smoking as a dichotomous yes/no measure. However, the risk of CVD associated with smoking also varies with the intensity and duration of smoking and there is a strong association between time since quitting and the risk of disease onset. This study aims to develop improved risk prediction equations for CVD incidence incorporating intensity and duration of smoking and time since quitting.The risk of developing a first CVD event was evaluated using a Cox's model for participants in the Framingham offspring cohort who attended the fourth examination (1988-92) between the ages of 30 and 74 years and were free of CVD (n=3751). The full models based on the smoking variables and other risk factors, and reduced models based on the smoking variables and non-laboratory risk factors demonstrated good discrimination, calibration and global fit. The incorporation of both time since quitting among past smokers and pack-years among current smokers resulted in better predictive performance as compared to a dichotomous current/non-smoker measure and a current/quitter/never smoker measure. Compared to never smokers, the risk of CVD incidence increased with pack-years. Risk among those quitting more than five years prior to the baseline exam and within five years prior to the baseline exam were similar and twice as high as that of never smokers. A CVD risk equation incorporating the effects of pack-years and time since quitting provides an improved tool to quantify risk and guide preventive care. PMID- 21977297 TI - Characterization of coronary plaques with combined use of intravascular ultrasound, virtual histology and optical coherence tomography. AB - According to post-mortem studies, luminal thrombosis occurs from plaque rupture, erosion and calcified nodules. In vivo studies have found thin cap fibroatheroma (TCFA) as the main vulnerable lesion, prone to rupture. Few data about other post mortem lesions have been reported in vivo. Our main objective is to characterize in vivo the coronary plaques with intravascular ultrasound-virtual histology (IVUS-VH) and optical coherence tomography (OCT), in order to detect not only thin cap fibroatheroma (TCFA), but also other possible vulnerable lesions. The secondary objective is to correlate these findings with clinical and analytical data. Twenty-five patients (18 stable) submitted to coronary angiography were included in this pilot study. After angiography, the three vessels were studied (when possible) with IVUS-VH and OCT. Plaque characteristics were correlated with clinical and analytical data. Forty-six lesions were analyzed. IVUS-VH detected significant necrotic core in 15 (3 were definite TCFA). OCT detected TCFA in 10 lesions, erosion in 6, thrombus in 5 and calcified nodule in 8. Possible vulnerable lesion was found in 61% of stable and 57% of unstable patients. Erosions and calcified nodules were only found in stable patients. Those with significant necrotic core had higher body mass index (P=0.016), higher levels of hs-CRP (P=0.019) and triglycerides (P=0.040). The higher the levels of hs-CRP, the larger the size of the necrotic core (r=0.69, P=0.003). Lesions with characteristics of vulnerability were detected by IVUS-VH and OCT in more than 50% of stable and unstable coronary patients. A significant necrotic core was mainly correlated with higher hs-CRP. PMID- 21977298 TI - Flexible band versus rigid ring annuloplasty for functional tricuspid regurgitation. AB - We review and compare our experience with tricuspid ring annuloplasty between usage of the Cosgrove-Edwards flexible band and the MC(3) rigid ring for repair of functional tricuspid regurgitation to determine the efficacy and mid-term durability of tricuspid annuloplasty. 117 patients with functional tricuspid regurgitation undergoing open heart surgery and tricuspid valve repair from May 2005 to December 2007 were reviewed. The flexible bands were used in thirty five patients before October 2006. Since then, the rigid rings were used in the next consecutive eighty two cases. Echocardiographic evaluation of tricuspid regurgitation was performed preoperatively and postoperatively in follow-up schedule. The degree of tricuspid regurgitation was reduced from 2.80+/-0.67 to 0.71+/-1.0 (regurgitation severity grade: 0 to 4) in the patients with flexible bands at discharge. It was from 2.68+/-0.70 to 0.22+/-0.60 in the patients with rigid rings. At thirty six months postoperative period, tricuspid regurgitation grades in patients with flexible bands and rigid rings were 0.80+/-0.95 and 0.36+/-0.77, respectively. Freedom from recurrent tricuspid regurgitation (grade 2 or 3) in patients with flexible bands and rigid rings were 68.6% and 87.8%, respectively. Recurrent tricuspid regurgitation was significantly lower in the patients with rigid rings. Although both flexible band and rigid ring annuloplasty provide low rate of recurrent tricuspid regurgitation, rigid ring annuloplasty might be more effective than flexible band annuloplasty for decreasing functional tricuspid regurgitation in immediate and mid-term postoperative periods. PMID- 21977299 TI - Bilateral coronary - pulmonary fistulae, diagnosed by transoesophageal echocardiogram. AB - Bilateral coronary artery fistulae to pulmonary artery is a rare condition. We diagnosed this condition by transoesophageal echocardiogram and successfully treated with surgery. PMID- 21977300 TI - Subclinical coronary atherosclerosis identified by coronary computed tomographic angiography in asymptomatic morbidly obese patients. AB - Obesity is a common public health problem and obese individuals in particular have a disproportionate incidence of acute coronary events. This study was undertaken to identify coronary artery lesions as well as associated clinical features, risk factors and demographics in patients with a body mass index (BMI) >40 kg/m(2) without known coronary artery disease (CAD). Morbidly obese subjects were prospectively recruited to undergo coronary computed tomographic angiography (CCTA) using a dual-source computed tomography (CT) system. CAD was defined as the presence of any atherosclerotic lesion in any one coronary artery segment. The presence, location, and severity of atherosclerosis were related to patient characteristics. Forty-one patients (28 women, mean age, 50.4+/-10.0 years, mean BMI, 43.8+/-4.8 kg/m(2)) served as the study population. Of these, 25 patients (61%) had at least one coronary stenosis. All but 2 patients within the CAD cohort had coronary artery calcium (CAC) scores >0, and most plaques identified (75.4%) were non-calcified. There was a predilection of calcified and non calcified atherosclerosis involving the left anterior descending (LAD) coronary artery compared with other coronary segments. Univariate predictors of CAD included older age, dyslipidemia, and diabetes. In this preliminary study of young morbidly obese patients, CCTA detected a high prevalence of calcified and non-calcified CAD, although the later predominated. PMID- 21977301 TI - Pseudo-dissection of ascending aorta in inferior myocardial infarction. AB - Acute aortic dissection is a cardiac emergency which can present as inferior myocardial infarction. It has high morbidity and mortality requiring prompt diagnosis and treatment. Rapid advances in non-invasive imaging have facilitated the early diagnosis of this condition and in ruling out this potentially catastrophic illness. We report an interesting case of a 57-year old man who presented with inferior myocardial infarction requiring thrombolysis and temporary pacing wire for complete heart block. An echocardiogram was highly suspicious of aortic dissection. CT scan confirmed that the malposition of the temporary pacing wire through the aorta mimicked aortic dissection. PMID- 21977302 TI - Malnutrition as assessed by nutritional risk index is associated with worse outcome in patients admitted with acute decompensated heart failure: an ACAP-HF data analysis. AB - Malnutrition is common at hospital admission and tends to worsen during hospitalization. This controlled population study aimed to determine if serum albumin or moderate and severe nutritional depletion by Nutritional Risk Index (NRI) at hospital admission are associated with increased length of hospital stay (LOS) in patients admitted with acute decompensated heart failure (ADHF). Serum albumin levels and lymphocyte counts were retrospectively determined at hospital admission in 1740 consecutive patients admitted with primary and secondary diagnosis of ADHF. The Nutrition Risk Score (NRI) developed originally in AIDS and cancer populations was derived from the serum albumin concentration and the ratio of actual to usual weight, as follows: NRI = (1.519 * serum albumin, g/dL) + {41.7 * present weight (kg)/ideal body weight(kg)}. Patients were classified into four groups as no, mild, moderate or severe risk by NRI. Multiple logistic regressions were used to determine the association between nutritional risk category and LOS.Three hundred and eighty-one patients (34%) were at moderate or severe nutritional risk by NRI score. This cohort had lower BMI (24 +/- 5.6 kg/m(2)), albumin (2.8+/-0.5 g/dL), mean NRI (73.5+/-9) and lower eGFR (50+/-33 mL/min per 1.73 m(2)). NRI for this cohort, adjusted for age, was associated with LOS of 10.1 days. Using the Multiple Logistic regression module, NRI was the strongest predictor for LOS (OR 1.7, 95% CI: 1.58-1.9; P=0.005), followed by TIMI Risk Score [TRS] (OR 1.33, 95% CI: 1.03-1.71; P=0.02) and the presence of coronary artery disease (OR 2.29, 95%CI: 1.03-5.1; P=0.04). Moderate and severe NRI score was associated with higher readmission and death rates as compared to the other two groups.Nutritional depletion as assessed by Nutritional Risk Index is associated with worse outcome in patients admitted with ADHF. Therefore; we recommend adding NRI to further risk stratify these patients. PMID- 21977303 TI - Pressure ulcer: an unreported complication of the Safeguard(r) hemostasis device. No need to crack under pressure. AB - Diagnostic cardiac catheterizations are predominantly performed using the femoral artery access. Several devices have been developed to aid in the closure of femoral arteriotomy.Safeguard(r) is a new pneumatic compression device that has been developed for compression of the femoral artery after brief manual compression. We hereby report the case of an elderly patient who underwent a percutaneous coronary intervention via the femoral artery in whom a SafeguardTM device, left overnight because of persistent oozing, provoked an extensive pressure ulcer. Knowledge of this potential complication is important to minimize its occurance and provide appropriate treatment. PMID- 21977304 TI - Association of interatrial septal abnormalities with cardiac impulse conduction disorders in adult patients: experience from a tertiary center in Kosovo. AB - INTERATRIAL SEPTAL DISORDERS, WHICH INCLUDE: atrial septal defect, patent foramen ovale and atrial septal aneurysm, are frequent congenital anomalies found in adult patients. Early detection of these anomalies is important to prevent their hemodynamic and/or thromboembolic consequences. The aims of this study were: to assess the association between impulse conduction disorders and anomalies of interatrial septum; to determine the prevalence of different types of interatrial septum abnormalities; to assess anatomic, hemodynamic, and clinical consequences of interatrial septal pathologies. Fifty-three adult patients with impulse conduction disorders and patients without ECG changes but with signs of interatrial septal abnormalities, who were referred to our center for echocardiography, were included in a prospective transesophageal echocardiography study. Interatrial septal anomalies were detected in around 85% of the examined patients. Patent foramen ovale was encountered in 32% of the patients, and in combination with atrial septal aneurysm in an additional 11.3% of cases. Atrial septal aneurysm and atrial septal defect were diagnosed with equal frequency in 20.7% of our study population. Impulse conduction disorders were significantly more suggestive of interatrial septal anomalies than clinical signs and symptoms observed in our patients (84.91% vs 30.19%, P=0.002). Right bundle branch block was the most frequent impulse conduction disorder, found in 41 (77.36%) cases. We conclude that interatrial septal anomalies are highly associated with impulse conduction disorders, particularly with right bundle branch block. Impulse conduction disorders are more indicative of interatrial septal abnormalities in earlier stages than can be understood from the patient's clinical condition. PMID- 21977305 TI - Single coronary artery from the right sinus of Valsalva. AB - We describe a case of a single coronary artery originating from the right coronary sinus and bifurcating into the left coronary artery (LCA) and right coronary artery (RCA) in a 74-year old woman, with a non-ST elevation acute myocardial infarction (NSTEMI). Diagnosis was made by coronary angiography which ruled out stenosis, and showed normal LCA and RCA branching. The connection path of LCA, with the opposite cusp, was defined retroaortic by multislice computed tomography (CT). The variants of this coronary anomaly, together with their clinical implications and pathophysiology of acute myocardial infarction (AMI) are discussed. Multislice CT is fundamental for clinical decision making. PMID- 21977306 TI - Accessory mitral valve tissue causing severe left ventricular outflow tract obstruction in a post-Senning patient with transposition of the great arteries. AB - Accessory mitral valve tissue is a rare congenital anomaly associated with congenital cardiac defects and is usually detected in the first decade of life. We describe the case of an 18-year old post-Senning asymptomatic patient who was found to have accessory mitral valve tissue on transthoracic echocardiography producing severe left ventricular outflow tract obstruction. PMID- 21977307 TI - Implications of turbulence slope variations in different approaches. AB - Both heart rate variability (HRV) and heart rate turbulence (HRT) are established tools to study cardiac autonomic activity. Short-term studies of HRV had been reported to be stable for autonomic function assessment. However, there is little information on whether short-term HRT assessment is comparable to 24 h assessment. The aim of the study is to identify the relationship of HRT values between the 24 h and isolated tachogram measurements. We collected 24 h Holter recordings from 116 patients attending the outpatient department. HRT parameters were assessed for 24 h. Using the conventional method, HRT parameters were calculated using the average of tachograms over long-term recordings. In an alternative method, HRT parameters were obtained from each tachogram. We calculated a mean value for each subject by averaging the whole HRT data of every tachogram. Correlation analysis between the two groups of HRT values was performed. The results showed a high correlation between the two methods in turbulence slope (TS) (P<0.001; r=0.84) and an extremely significant correlation in turbulence onset (TO) (P<0.001; r=0.99). The values of TS were increased when assessed by separate tachogram. The variations became prominent when TS values calculated by the conventional method were low. HRT is as useful by separate tachogram assessment as by the standard Holter recordings. However, the TS values should be redefined. In subjects with abnormal turbulence slope (<2.5) calculated by averaging long-term recordings, the possibility of TS values blunted by diverse regression slope sequences in separate tachograms should be taken into consideration. PMID- 21977308 TI - Does high-dose metformin cause lactic acidosis in type 2 diabetic patients after CABG surgery? A double blind randomized clinical trial. AB - Metformin is a dimethyl biguanide oral anti-hyperglycemic agent. Lactic acidosis due to metformin is a fatal metabolic condition that limits its use in patients in poor clinical condition, consequently reducing the number of patients who benefit from this medication. In a double blind randomized clinical trial, we investigated 200 type 2 diabetic patients after coronary artery bypass surgery in the open heart ICU of the Mazandaran Heart Center, and randomly assigned them to equal intervention and control groups. The intervention group received regular insulin infusion along with 2 metformin 500 mg tablets every twelve hours, while the control group received only intravenous insulin with 2 placebo tablets every twelve hours. Lactate level, pH, base excess, blood glucose and serum creatinine were measured over five 12 h periods, with data averaged for each period. The primary outcome in this study was high lactate levels. Comparison between the 2 groups was made by independent Student's t-test. To compare changes in multiple measures in each group and analysis of group interaction, a repeated measurement ANOVA test was used.There was no significant difference between the 2 groups regarding pH, base excess, or bicarbonate intake (P>0.05). No patient showed lactic acidosis in either group. Lactate levels were 23.0 vs 23.4 in the insulin metformin and insulin only groups when the study was started, respectively. At the end of the study, those levels were 18.7 vs 18.9, respectively. In addition, the ANOVA repeated measurement test did not show a significant difference in terms of changes in the amount of lactate level between the 2 groups during the five measurement tests of the study period (P>0.05).High-dose metformin (1,000 mg twice daily with insulin) does not cause lactic acidosis in type 2 diabetic patients after coronary artery bypass surgery. PMID- 21977310 TI - Small interfering RNA efficiently suppresses adhesion molecule expression on pulmonary microvascular endothelium. AB - Background. Adhesion molecules are known to influence postoperative organ function, they are hardly involved in the inflammatory response following the ischemia-reperfusion injury. We sought to investigate the potency of small interfering RNAs to suppress adhesion molecule expression in human pulmonary microvascular endothelial cells. Methods. Human lung microvascular endothelial cells were transfected with specific siRNA followed by a stimulation of the cells with an inflammatory cytokine. Adhesion molecule expression was determined by FACS-analysis, and reduction of intracellular mRNA was determined by qRT-PCR. Furthermore, the attachment of isolated neutrophils on the endothelial layer was determined after siRNA transfection. Results. In summary, siRNA transfection significantly decreased the percentage positive cells in a single cocktail transfection of each adhesion molecule investigated. Adhering neutrophils were diminished as well. Conclusion. siRNA might be a promising tool for the effective suppression of adhesion molecule expression on pulmonary microvascular cells, potentially minimizing leukocyte-endothelial depending interactions of a pulmonary allograft. PMID- 21977311 TI - Yeast extract promotes cell growth and induces production of polyvinyl alcohol degrading enzymes. AB - Polyvinyl alcohol-degrading enzymes (PVAases) have a great potential in bio desizing processes for its low environmental impact and low energy consumption. In this study, the effect of yeast extract on PVAases production was investigated. A strategy of four-point yeast extract addition was developed and applied to maximize cell growth and PVAases production. As a result, the maximum dry cell weight achieved was 1.48 g/L and the corresponding PVAases activity was 2.99 U/mL, which are 46.5% and 176.8% higher than the control, respectively. Applying this strategy in a 7 L fermentor increased PVAases activity to 3.41 U/mL. Three amino acids (glycine, serine, and tyrosine) in yeast extract play a central role in the production of PVAases. These results suggest that the new strategy of four-point yeast extract addition could benefit PVAases production. PMID- 21977309 TI - Non-B DNA Secondary Structures and Their Resolution by RecQ Helicases. AB - In addition to the canonical B-form structure first described by Watson and Crick, DNA can adopt a number of alternative structures. These non-B-form DNA secondary structures form spontaneously on tracts of repeat sequences that are abundant in genomes. In addition, structured forms of DNA with intrastrand pairing may arise on single-stranded DNA produced transiently during various cellular processes. Such secondary structures have a range of biological functions but also induce genetic instability. Increasing evidence suggests that genomic instabilities induced by non-B DNA secondary structures result in predisposition to diseases. Secondary DNA structures also represent a new class of molecular targets for DNA-interactive compounds that might be useful for targeting telomeres and transcriptional control. The equilibrium between the duplex DNA and formation of multistranded non-B-form structures is partly dependent upon the helicases that unwind (resolve) these alternate DNA structures. With special focus on tetraplex, triplex, and cruciform, this paper summarizes the incidence of non-B DNA structures and their association with genomic instability and emphasizes the roles of RecQ-like DNA helicases in genome maintenance by resolution of DNA secondary structures. In future, RecQ helicases are anticipated to be additional molecular targets for cancer chemotherapeutics. PMID- 21977312 TI - Isolation, Purification, and Characterization of Fungal Laccase from Pleurotus sp. AB - Laccases are blue copper oxidases (E.C. 1.10.3.2 benzenediol: oxygen oxidoreductase) that catalyze the one-electron oxidation of phenolics, aromatic amines, and other electron-rich substrates with the concomitant reduction of O(2) to H(2)O. They are currently seen as highly interesting industrial enzymes because of their broad substrate specificity. A positive strain was isolated and characterized as nonspore forming Basidiomycetes Pleurotus sp. Laccase activity was determined using ABTS as substrate. Laccase was purified by ionexchange and gel filtration chromatography. The purified laccase was a monomer showed a molecular mass of 40 +/- 1 kDa as estimated by SDS-PAGE and a 72-fold purification with a 22% yield. The optimal pH and temperature were 4.5 and 65( degrees )C, respectively. The K(m) and V(max) values are 250 (mM) and 0.33 (MUmol/min), respectively, for ABTS as substrate. Metal ions like CuSO(4), BaCl(2), MgCl(2), FeCl(2), ZnCl(2) have no effect on purified laccase whereas HgCl(2) and MnCl(2) moderately decrease enzyme activity. SDS and sodium azide inhibited enzyme activity, whereas Urea, PCMB, DTT, and mercaptoethanol have no effect on enzyme activity. The isolated laccase can be used in development of biosensor for detecting the phenolic compounds from the effluents of paper industries. PMID- 21977313 TI - The role of manganese superoxide dismutase in inflammation defense. AB - Antioxidant enzymes maintain cellular redox homeostasis. Manganese superoxide dismutase (MnSOD), an enzyme located in mitochondria, is the key enzyme that protects the energy-generating mitochondria from oxidative damage. Levels of MnSOD are reduced in many diseases, including cancer, neurodegenerative diseases, and psoriasis. Overexpression of MnSOD in tumor cells can significantly attenuate the malignant phenotype. Past studies have reported that this enzyme has the potential to be used as an anti-inflammatory agent because of its superoxide anion scavenging ability. Superoxide anions have a proinflammatory role in many diseases. Treatment of a rat model of lung pleurisy with the MnSOD mimetic MnTBAP suppressed the inflammatory response in a dose-dependent manner. In this paper, the mechanisms underlying the suppressive effects of MnSOD in inflammatory diseases are studied, and the potential applications of this enzyme and its mimetics as anti-inflammatory agents are discussed. PMID- 21977315 TI - Distinct effects of calorie restriction and resveratrol on diet-induced obesity and Fatty liver formation. AB - The potential of resveratrol to mimic beneficial effects of calorie restriction (CR) was investigated. We compared the effects of both CR (70% of ad libitum energy intake) or resveratrol (2 g/kg or 4 g/kg food) on high-fat diet-induced obesity and fatty liver formation in C57Bl/6J mice, and we examined their effects on calorimetry, metabolic performance, and the expressions of inflammatory genes and SIRT proteins. We found that resveratrol with 4 g/kg dose partially prevented hepatic steatosis and hepatocyte ballooning and induced skeletal muscle SIRT1 and SIRT4 expression while other examined parameter were unaffected by resveratrol. In contrast, CR provided superior protection against diet-induced obesity and fatty liver formation as compared to resveratrol, and the effects were associated with increased physical activity and ameliorated adipose tissue inflammation. CR increased expressions of SIRT3 in metabolically important tissues, suggesting that the beneficial effects of CR are mediated, at least in part, via SIRT3 dependent pathways. PMID- 21977316 TI - Lifestyle modification to promote weight loss in the absence of energy restriction. PMID- 21977314 TI - Mindfulness Intervention for Stress Eating to Reduce Cortisol and Abdominal Fat among Overweight and Obese Women: An Exploratory Randomized Controlled Study. AB - Psychological distress and elevated cortisol secretion promote abdominal fat, a feature of the Metabolic Syndrome. Effects of stress reduction interventions on abdominal fat are unknown. Forty-seven overweight/obese women (mean BMI = 31.2) were randomly assigned to a 4-month intervention or waitlist group to explore effects of a mindfulness program for stress eating. We assessed mindfulness, psychological distress, eating behavior, weight, cortisol awakening response (CAR), and abdominal fat (by dual-energy X-ray absorptiometry) pre- and posttreatment. Treatment participants improved in mindfulness, anxiety, and external-based eating compared to control participants. Groups did not differ on average CAR, weight, or abdominal fat over time. However, obese treatment participants showed significant reductions in CAR and maintained body weight, while obese control participants had stable CAR and gained weight. Improvements in mindfulness, chronic stress, and CAR were associated with reductions in abdominal fat. This proof of concept study suggests that mindfulness training shows promise for improving eating patterns and the CAR, which may reduce abdominal fat over time. PMID- 21977317 TI - Eating disorders and major depression: role of anger and personality. AB - This study aimed to evaluate comorbidity for MD in a large ED sample and both personality and anger as clinical characteristics of patients with ED and MD. We assessed 838 ED patients with psychiatric evaluations and psychometric questionnaires: Temperament and Character Inventory, Eating Disorder Inventory-2, Beck Depression Inventory, and State-Trait Anger Expression Inventory. 19.5% of ED patients were found to suffer from comorbid MD and 48.7% reported clinically significant depressive symptomatology: patients with Anorexia Binge-Purging and Bulimia Nervosa were more likely to be diagnosed with MD. Irritable mood was found in the 73% of patients with MD. High Harm Avoidance (HA) and low Self Directedness (SD) predicted MD independently of severity of the ED symptomatology, several clinical variables, and ED diagnosis. Assessing both personality and depressive symptoms could be useful to provide effective treatments. Longitudinal studies are needed to investigate the pathogenetic role of HA and SD for ED and MD. PMID- 21977318 TI - ROS-Mediated Signalling in Bacteria: Zinc-Containing Cys-X-X-Cys Redox Centres and Iron-Based Oxidative Stress. AB - Bacteria are permanently in contact with reactive oxygen species (ROS), both over the course of their life cycle as well that present in their environment. These species cause damage to proteins, lipids, and nucleotides, negatively impacting the organism. To detect these ROS molecules and to stimulate the expression of proteins involved in antioxidative stress response, bacteria use a number of different protein-based regulatory and sensory systems. ROS-based stress detection mechanisms induce posttranslational modifications, resulting in overall conformational and structural changes within sensory proteins. The subsequent structural rearrangements result in changes of protein activity, which lead to regulated and appropriate response on the transcriptional level. Many bacterial enzymes and regulatory proteins possess a conserved signature, the zinc containing redox centre Cys-X-X-Cys in which a disulfide bridge is formed upon oxidative stress. Other metal-dependent oxidative modifications of amino acid side-chains (dityrosines, 2-oxo-histidines, or carbonylation) also modulate the activity of redox-sensitive proteins. Using molecular biology, biochemistry, biophysical, and structure biology tools, molecular mechanisms involved in sensing and response to oxidative stress have been elucidated in detail. In this review, we analyze some examples of bacterial redox-sensing proteins involved in antioxidative stress response and focus further on the currently known molecular mechanism of function. PMID- 21977320 TI - Association between Cystatin C and MRI Measures of Left Ventricular Structure and Function: Multi-Ethnic Study of Atherosclerosis. AB - Introduction. Reduced kidney function, approximated by elevated cystatin C, is associated with diastolic dysfunction, heart failure, and cardiovascular mortality; however, the precise mechanism(s) that account for these relationships remains unclear. Understanding the relationship between cystatin C and subclinical left ventricular (LV) remodeling, across ethnically diverse populations, may help explain the mechanisms underlying the association of kidney dysfunction with heart failure and cardiovascular mortality. Methods. Measures of cystatin C and LV parameters were obtained from the multi-ethnic study of atherosclerosis (MESA) cohort at baseline (N = 4, 970 with complete data on cystatin C and LV parameters). LV parameters; LV end-diastolic (LVEDV) and end systolic volumes (LVESV), LV mass (LVM), concentricity (LV mass/LV end-diastolic volume), and LV ejection fraction (LVEF) were measured using magnetic resonance imaging. Nested linear models were used to examine the relationship between higher quartiles of cystatin C and LV parameters, with and without adjustment for demographics, height, and weight, and traditional cardiovascular risk factors. Similar analyses were performed stratified by ethnicity and gender. Results. A fully adjusted model demonstrated a linear relationship between higher quartiles of cystatin C and lower LVEDV, (Mean +/- SE, 128 +/- 0.7, 128 +/- 0.7, 126 +/- 0.7, 124 +/- 0.8 mL; P = 0.0001). Associations were also observed between higher quartiles of cystatin C and lower LVESV (P = 0.04) and concentricity (P = 0.0001). In contrast, no association was detected between cystatin C and LVM or LVEF. In analyses stratified by race and gender, the patterns of association between cystatin C quartiles and LV parameters were qualitatively similar to the overall association. Conclusion. Cystatin C levels were inversely associated with LVEDV and LVESV with a disproportionate decrease in LVEDV compared to LVM in a multi-ethnic population. This morphometric pattern of concentric left ventricular remodeling, may in part explain the process by which kidney dysfunction leads to diastolic dysfunction, heart failure and cardiovascular mortality. PMID- 21977321 TI - Purple urine bag syndrome: an alarming hue? A brief review of the literature. AB - Purple urine bag syndrome (PUBS) is a unique disease entity characterized by an alarming purple discoloration of the urine secondary to recurrent urinary tract infections with indigo- and indirubin-producing bacteria. It is usually associated with prolonged urinary catheterization and chronic debilitated states. We hereby present a concise review of this rare phenomenon with historic perspectives, epidemiology, emphasizing on current concepts of etiology, pathogenesis, relevant clinical associations, treatment modalities, prognosis, and future directions in PUBS. In addition, we highlight an interesting occurrence of this intriguing phenomenon in a 39-year-old gentleman at our institution. PMID- 21977322 TI - Cognitive beliefs and future time perspectives: predictors of mortality and longevity. AB - On the basis of postulates derived from cognitive-behavioral theory, research and therapy, the authors explored the extent to which older adults' cognitive beliefs of a just world and their perspectives on future time and similarity or self continuity with the future self are predictors of long-term survival. After baseline assessment of health and cognitive beliefs and future perspectives of time and self-continuity as predictors of mortality, 440 participants (ages 65 to 87) were followed longitudinally for 6.5 years. Consistent with our hypotheses, findings demonstrated that a significantly higher percentage of survivors were individuals who showed higher scores on beliefs in a just world and on both the future time perspective and the future self-continuity perspective at the time of baseline assessments. Conversely, mortality risk was much higher for individuals who scored low on these predictor variables, and high on distrust. Implications for health and longevity are discussed. PMID- 21977323 TI - Recurrence of congenital heart disease in cases with familial risk screened prenatally by echocardiography. AB - OBJECTIVES: To evaluate the recurrence of congenital heart disease (CHD) in pregnant women with familial risk who had been referred for fetal echocardiography. MATERIAL AND METHODS: 1634 pregnancies from 1483 women with familial history of CHD in one or more relatives were studied. Fetal cardiologic diagnosis was compared with postnatal findings at 6 months or at autopsy. RESULTS: Total recurrence rate of CHD was 3.98%, 4.06% in single familial risk, 2.9% in double, and 5% in multiple risk. It was 3.5% in case of one previously affected child; 4.5% with 2 children; 5.2% with the mother alone affected and 7,5% with father alone affected and 3.5% with a single distant relative. Exact concordance of CHD was found in 21.5% and a partial concordance in 20% of cases. CONCLUSIONS: Our data show a higher recurrence rate of CHD than previously published data and high relative risk ratios compared to normal population. PMID- 21977319 TI - Oxidative stress, mitochondrial dysfunction, and aging. AB - Aging is an intricate phenomenon characterized by progressive decline in physiological functions and increase in mortality that is often accompanied by many pathological diseases. Although aging is almost universally conserved among all organisms, the underlying molecular mechanisms of aging remain largely elusive. Many theories of aging have been proposed, including the free-radical and mitochondrial theories of aging. Both theories speculate that cumulative damage to mitochondria and mitochondrial DNA (mtDNA) caused by reactive oxygen species (ROS) is one of the causes of aging. Oxidative damage affects replication and transcription of mtDNA and results in a decline in mitochondrial function which in turn leads to enhanced ROS production and further damage to mtDNA. In this paper, we will present the current understanding of the interplay between ROS and mitochondria and will discuss their potential impact on aging and age related diseases. PMID- 21977324 TI - Bradykinin type-2 receptor expression correlates with age and is subjected to transcriptional regulation. AB - Accumulating work in experimental animals suggests that bradykinin (BK) exerts cardioprotective effects via bradykinin type-2 receptors (BK-2Rs). In human end stage heart failure, BK-2Rs are significantly downregulated by mechanisms that have remained elusive. Heart tissues from idiopathic dilated cardiomyopathy (IDC; n = 7), coronary heart disease (CHD; n = 6), and normal patients (n = 6) were analyzed by RT-PCR, SSCP, and Western blotting. In normal and IDC hearts, BK-2R expression increased with age, with a lower relative increase in IDC hearts. BK 2R mRNA and protein levels showed a positive linear correlation, suggesting transcriptional regulation. Two known BK-2R promoter polymorphisms, -58T/C and 9/+9, were found to be present in the study population. The allelic frequencies for the C-allele in -58T/C were 0.58 in normal and CHD hearts and 0.81 in IDC hearts. Furthermore, the allelic frequencies for the -9 and +9 alleles were 0.42 and 0.58 in normal hearts and 0.64 and 0.36 in IDC hearts, respectively. All analyzed CHD hearts were homozygous for the -9 allele. Thus, the expression of cardioprotective BK-2Rs in human hearts is increased with age in normal and IDC hearts and may be regulated on the transcriptional level. Moreover, comparison of normal subjects and patients with failing hearts revealed different allelic frequencies in each of two known BK-2R gene polymorphisms. PMID- 21977325 TI - Lipofundin-induced hyperlipidemia promotes oxidative stress and atherosclerotic lesions in new zealand white rabbits. AB - Atherosclerosis represents a major cause of death in the world. It is known that Lipofundin 20% induces atherosclerotic lesions in rabbits, but its effects on serum lipids behaviour and redox environment have not been addressed. In this study, New Zealand rabbits were treated with 2 mL/kg of Lipofundin for 8 days. Then, redox biomarkers and serum lipids were determined spectrophotometrically. On the other hand, the development of atherosclerotic lesions was confirmed by eosin/hematoxylin staining and electron microscopy. At the end of the experiment, total cholesterol, triglycerides, cholesterol-LDL, and cholesterol-HDL levels were significantly increased. Also, a high index of biomolecules damage, a disruption of both enzymatic and nonenzymatic defenses, and a reduction of nitric oxide were observed. Our data demonstrated that Lipofundin 20% induces hyperlipidemia, which promotes an oxidative stress state. Due to the importance of these phenomena as risk factors for atherogenesis, we suggest that Lipofundin induces atherosclerosis mainly through these mechanisms. PMID- 21977326 TI - Fermentative Production and Thermostability Characterization of alpha Amylase from Aspergillus Species and Its Application Potential Evaluation in Desizing of Cotton Cloth. AB - The production of extracellular amylase was investigated employing our laboratory isolate, Aspergillus niger sp. MK 07 and effect of process variables on enzyme production, was studied in a fermentor. It was found that amylase production was maximum when the fermentor volume was maintained at 70%, rate of agitation at 250 rpm, air supply at 2.5 vvm, inoculum concentration of 10%, and a pH of 5.0. Highest enzyme production obtained under all optimized conditions was 1734 U/mL with sucrose as carbon substrate and corn steep liquor as nitrogen source. Enzyme purification studies by ammonium sulphate precipitation and Sephadex G-100 chromatography was evaluated for obtaining purified enzyme. Thermostability of amylase were evaluated with varying concentrations from 0.2 to 0.5 M concentrations of calcium chloride and the highest activity obtained was 3115 U/mL with 0.3 M calcium chloride at 55 degrees C. Effect of temperature and pH on the activity of purified enzyme was evaluated and the purified enzyme showed an activity till 75 degrees C and a pH of 6.5. Application potential of partially purified alpha amylase on desizing of cotton cloth was evaluated with varying enzyme concentrations from 50 to 500 U/mL and the highest desizing activity was found to be at 300 U/mL. PMID- 21977327 TI - Controversies in the adjuvant therapy of endometrial cancer. AB - Endometrial cancer is the most common malignancy of the female genital tract. Surgical treatment includes hysterectomy, bilateral salpingo-oophorectomy, and an appropriate staging procedure. Relapse of endometrial cancer may occur in patients with high risk factors, such as old age, grade 3 cancer, deep myometrial invasion, and papillary serous and clear cell types. In recent years, several randomized trials reported the results of adjuvant therapy for patients with high risk factors. Nonetheless, some controversies still exist. This paper presents and discusses the results of important randomized trials of adjuvant therapy for endometrial cancer with risk factors. PMID- 21977328 TI - Experience of emergency peripartum hysterectomies at a tertiary care hospital in quetta, pakistan. AB - Emergency peripartum hysterectomy (EPH) is associated with significant morbidity and mortality worldwide. The purpose of our paper was to determine the incidence, morbidity, and mortality of EPH done at our institution; the largest tertiary care government hospital in the city of Quetta, Pakistan. During the study period there were 12,642 deliveries, out of which 46 women had undergone an EPH, translating into an incidence of ~4 per 1,000 births. Disturbingly, 82.6% of these patients had received no antenatal care prior to their presentation. There were 4 (8.7%) maternal deaths and 31 (67.4%) perinatal deaths. The commonest indication noted was uterine rupture in 21 (45.7%) cases. Lack of antenatal care is indeed a modifiable factor that needs to be addressed to help reduce maternal and fetal morbidity/mortality not only from emergency hysterectomies but also from all other preventable causes. PMID- 21977330 TI - Closing the osteoporosis care gap in hip fracture patients: an opportunity to decrease recurrent fractures and hospital admissions. AB - Background. Falls and hip fractures are an increasing health threat to older people who often never return to independent living. This study examines the management of bone health in an acute care setting following a hip fracture in patients over age 65. Methods. Retrospective chart review of all patients admitted to a tertiary health facility who suffered a recent hip fracture. Results. 420 charts of patients admitted over the course of a year (May 1, 2007 April 31, 2008) were reviewed. Thirty-seven percent of patients were supplemented with calcium on discharge, and 36% were supplemented with vitamin D on discharge. Thirty-one percent were discharged on a bisphosphonate. Conclusion. A significant care gap still exists in how osteoporosis is addressed despite guidelines on optimal management. A call to action is required by use of multifaceted approaches to bridge the gap, ensuring that fracture risk is minimized for the aging population. PMID- 21977329 TI - Toll-like receptors and myocardial inflammation. AB - Toll-like receptors (TLRs) are a member of the innate immune system. TLRs detect invading pathogens through the pathogen-associated molecular patterns (PAMPs) recognition and play an essential role in the host defense. TLRs can also sense a large number of endogenous molecules with the damage-associated molecular patterns (DAMPs) that are produced under various injurious conditions. Animal studies of the last decade have demonstrated that TLR signaling contributes to the pathogenesis of the critical cardiac conditions, where myocardial inflammation plays a prominent role, such as ischemic myocardial injury, myocarditis, and septic cardiomyopathy. This paper reviews the animal data on (1) TLRs, TLR ligands, and the signal transduction system and (2) the important role of TLR signaling in these critical cardiac conditions. PMID- 21977331 TI - Pattern and risk factors of central compartment lymph node metastasis in papillary thyroid cancer: a prospective study from an endocrine surgery centre. AB - Lymphatic metastasis in papillary thyroid cancer (PTC) is eminent; however, the extent of central compartment lymph nodes dissection (CCD) is controversial and requires the knowledge of pattern and risk factors for central compartment lymph nodes metastasis (CCM). We did a prospective study of 47 cases with PTC who underwent total thyroidectomy (TT) with CCD with/without lateral lymph nodes dissection (LND). Clinicopathological profile including CCM as ipsilateral and contralateral was documented. On histopathology, the mean tumour size was 3.57 +/ 2.42 cm 59.6% had CCM, which was bilateral in the majority (60.72%). The tumour size was the most important predictor for lymph nodes metastasis-(P=0.018) whereas multicentricity-(P=0.002) and ipsilateral CCM-(P=0.001) were the predictors for contralateral CCM. The long-term morbidity of CCD done in primary setting is comparable with TT-alone. Bilateral CCD should be done with thyroidectomy in PTC, otherwise the risk of residual diseases and subsequent recurrence is high. The long-term morbidity is comparable in experienced hands. PMID- 21977333 TI - Acoustic Analysis of PD Speech. AB - According to the U.S. National Institutes of Health, approximately 500,000 Americans have Parkinson's disease (PD), with roughly another 50,000 receiving new diagnoses each year. 70%-90% of these people also have the hypokinetic dysarthria associated with PD. Deep brain stimulation (DBS) substantially relieves motor symptoms in advanced-stage patients for whom medication produces disabling dyskinesias. This study investigated speech changes as a result of DBS settings chosen to maximize motor performance. The speech of 10 PD patients and 12 normal controls was analyzed for syllable rate and variability, syllable length patterning, vowel fraction, voice-onset time variability, and spirantization. These were normalized by the controls' standard deviation to represent distance from normal and combined into a composite measure. Results show that DBS settings relieving motor symptoms can improve speech, making it up to three standard deviations closer to normal. However, the clinically motivated settings evaluated here show greater capacity to impair, rather than improve, speech. A feedback device developed from these findings could be useful to clinicians adjusting DBS parameters, as a means for ensuring they do not unwittingly choose DBS settings which impair patients' communication. PMID- 21977334 TI - Primary small cell neuroendocrine carcinoma of vagina: a rare case report. AB - Primary small cell neuroendocrine carcinoma of vagina is an extremely rare disease. There have been only 26 previously reported cases in literature. Here, we report a case of primary small cell neuroendocrine carcinoma of vagina. Immunohistochemistry (IHC) showed tumor cells positive for synaptophysin, chromogranin, and neuron-specific enolase (NSE). PMID- 21977332 TI - Prognostic factors of papillary and follicular carcinomas in Japan based on data of kuma hospital. AB - There are some important prognostic factors for papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). In this paper, clinicopathological features significantly affecting patient prognosis are described based on our data as well as others. Distant metastasis at diagnosis is the most important prognostic factor for both PTC and FTC. Other than that, preoperative and intraoperative findings are important to evaluate the biological behavior of PTC. Extrathyroid extension, large lymph-node metastasis, and extranodal tumor extension that can be evaluated preoperatively or intraoperatively are significant prognostic factors for PTC patients. In contrast, pathological findings are important not only for diagnosis of FTC, but also for the evaluation of its biological character. Grade of invasiveness (minimally or widely invasive) and degree of differentiation (well differentiated or including a poorly differentiated component) greatly affect the prognosis of FTC patients. PMID- 21977336 TI - Predictors of extubation success in patients with middle cerebral artery acute ischemic stroke. AB - Introduction. Stroke patients often meet respiratory guidelines for extubation, but uncertainty exists if patients will protect their airway due to impaired mental status. Patients with middle cerebral artery (MCA) acute ischemic stroke (AIS) might have specific predictors of successful extubation. Methods. Retrospective cohort of MCA AIS patients requiring intubation. Results. Thirty seven MCA AIS patients were extubated successfully and ten failed extubation. Those who successfully extubated had higher extubation composite and eye response Glasgow Coma Scale (GCS) scores compared to those who failed (median 10T (IQR 9T 11T) versus 9.5T (8T-10T), P = 0.047, and 4 (3-4) versus 2.5 (1-3), P < 0.01). When adjusted for age, admission National Institutes of Health Stroke Scale score and laterality, patients with a GCS score >=8T trended toward extubating successfully (OR 23.30 (CI 0.94-580.27), P = 0.055). Conclusions. The GCS score might be important in predicting successful extubation in MCA AIS patients. Further prospective study is warranted to better assess factors predictive of extubation outcome in stroke and other brain-injured patients. PMID- 21977335 TI - Pathophysiology of the Behcet's Disease. AB - Behcet's disease (BD) is a multisystemic disease of unknown etiology characterized by chronic relapsing oral-genital ulcers and uveitis. Multiple systemic associations including articular, gastrointestinal, cardiopulmonary, neurologic, and vascular involvement are also observed in BD. Although the etiopathogenesis of the disease remains unknown, increased neutrophil functions such as chemotaxis, phagocytosis, and excessive production of reactive oxygen species (ROS), including superoxide anion, which may be responsible for oxidative tissue damage seen in BD, and also immunological alterations, T lymphocyte abnormalities in both subpopulation and function have been considered to be correlated with the etiopathogenesis of BD. There is some clinical evidence suggesting that emotional stress and hormonal alterations can influence the course and disease activity of BD. PMID- 21977337 TI - Using formative research to design an epidemiologic survey: the north Carolina study of home care and hospice nurses. AB - OBJECTIVES: Formative research can serve as a means of obtaining important information for designing an epidemiologic study, but descriptions of this approach in the epidemiologic literature are lacking. The objective of this paper is to describe the use of three formative research techniques in designing a survey of home care and hospice nurses. METHODS: We conducted two focus groups, seven key informant interviews, and approximately fifteen hours of direct observation among home care and hospice nurses recruited by word of mouth in North Carolina in 2006. RESULTS: We used information obtained from the formative research to decide which survey design would likely be most successful with this population (mail survey, as opposed to Internet survey or in-person interviews), which measure to use for the denominator of the blood exposure incidence rates (number of visits, as opposed to patient-time), and which items and response options to include in the questionnaire, as well as to identify specific survey techniques that would likely increase the response rate (emphasizing the regional focus of the study; sending the questionnaire to the home address). CONCLUSION: When particular information for planning a study is unavailable from the literature or the investigator's experience, formative research can be an effective means of obtaining that information. PMID- 21977338 TI - Treatment of generalized anxiety disorder: a comprehensive review of the literature for psychopharmacologic alternatives to newer antidepressants and benzodiazepines. AB - OBJECTIVE: Generalized anxiety disorder (GAD) is common, chronic, and debilitating. Treatment with benzodiazepines and newer antidepressants is often inadequate. This article reviews the effectiveness of alternative and augmenting medications, such as older antidepressants, antipsychotics, anticonvulsants, and beta-blockers. DATA SOURCES: A search using MEDLINE (1980 to week 4 of May 2010) with the key words generalized anxiety disorder or GAD and therapeutics or treatment was conducted. Articles included adult patients with a GAD diagnosis that established chronicity of illness. These included a small number of studies that used DSM-III criteria but added a chronicity of symptoms and included all studies that used DSM-III-R and DSM-IV criteria. Articles that did not include medications or that exclusively focused on newer antidepressants (selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, bupropion, and mirtazapine), buspirone, benzodiazepines, or herbal or investigational medications were excluded. Review articles and non-English language articles were also excluded. RESULTS: Thirty-six studies were reviewed. All of the references were then analyzed, and key portions were extracted. Many studies were open trials. Double-blind, placebo-controlled studies with imipramine, risperidone, olanzapine, hydroxyzine, ondansetron, tiagabine, valproate, and pregabalin had been conducted. Imipramine, hydroxyzine, valproate, and pregabalin were the most effective, although risperidone, olanzapine, ziprasidone, and aripiprazole may also reduce symptoms. CONCLUSIONS: Several medication strategies can be considered as promising alternatives or augmenting to antidepressant or benzodiazepine therapy in GAD. PMID- 21977339 TI - A psychosomatic perspective on takotsubo cardiomyopathy: a case report. AB - Takotsubo cardiomyopathy is a reversible heart condition initially described in the Japanese literature in the 1990s. The typical presentation mimics an acute coronary syndrome. It is frequently found in elderly women in the context of emotional or physical stress in the absence of significant obstructive coronary disease. The prognosis of the disease is favorable just with supportive care, but little is known about recurrence. The association between onset of Takotsubo cardiomyopathy and emotional triggers is striking but has received little attention in the psychiatric literature. On the basis of current evidence, we suggest consideration of beta-blockers for recurrence prevention. PMID- 21977340 TI - Use of complementary and alternative medicine by patients with cancer. PMID- 21977341 TI - Venlafaxine for the treatment of hormonal therapy-induced hot flashes in a male patient. PMID- 21977342 TI - Prescribing topiramate in patients with borderline personality disorder and a history of anorexia nervosa: a case report. PMID- 21977343 TI - From Lithium Intoxication to Lung Cancer: A Woman's Diagnostic Journey. PMID- 21977344 TI - Frontotemporal dementia-a chameleon? PMID- 21977345 TI - A cardiometabolic psychiatry consultation service in a state psychiatric hospital. PMID- 21977346 TI - Relapse after switching antidepressants because of tamoxifen use: a report of 2 cases. PMID- 21977347 TI - A case of cardiac arrest and pulmonary embolism after clozapine titration. PMID- 21977348 TI - Inhaled steroid-induced mania in an adolescent girl: a case report. PMID- 21977349 TI - "I choked my wife again!"-a case report. PMID- 21977350 TI - Diagnosis of pulmonary thromboembolism in psychiatric patients. PMID- 21977351 TI - Four cases of chronic pain that improved dramatically following low-dose aripiprazole administration. PMID- 21977352 TI - Misconceptions about the safety of ingesting methanol-based solid fuels: a case report. PMID- 21977353 TI - A 10-month, open-label evaluation of desvenlafaxine in outpatients with major depressive disorder. AB - BACKGROUND: The primary objective was to evaluate the long-term safety of desvenlafaxine (administered as desvenlafaxine succinate) during open-label treatment in adult outpatients with a primary DSM-IV diagnosis of major depressive disorder (MDD). METHOD: Depressed adult outpatients (>= 18 years) who had completed 8-week, double-blind therapy (desvenlafaxine, venlafaxine extended release, or placebo) in a phase 3 study of desvenlafaxine for MDD received up to 10 months of open-label treatment with flexible-dose desvenlafaxine (200 to 400 mg/d). Safety assessments included physical examination, measurement of weight and vital signs, laboratory determinations, and 12-lead electrocardiogram recordings. Adverse events (AEs) and discontinuations due to AEs were monitored throughout the trial. The primary efficacy outcome was mean change from baseline on 17-item Hamilton Depression Rating Scale (HDRS-17) total score. The trial was conducted from August 2003 to March 2006. RESULTS: The safety population included 1,395 patients who took at least 1 dose of open-label desvenlafaxine. Treatment emergent AEs were reported by 1,238 of 1,395 patients (89%) during the open label, on-therapy period. Treatment-emergent AEs reported by 10% or more patients were headache, nausea, hyperhidrosis, dizziness, dry mouth, insomnia, upper respiratory infection, nasopharyngitis, and fatigue. Adverse events were the primary reason for study discontinuation in 296 of 1,395 patients (21%). Ten patients (< 1%) had serious AEs that were considered possibly, probably, or definitely related to the study drug during the on-therapy period. No deaths occurred during the study. CONCLUSIONS: Desvenlafaxine can be safely administered for up to 12 months. No new safety findings were observed in this study. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01309542. PMID- 21977354 TI - Rates of detection of mood and anxiety disorders in primary care: a descriptive, cross-sectional study. AB - OBJECTIVE: To determine the incidence of major depressive disorder, bipolar disorder, panic disorder, social anxiety disorder, and generalized anxiety disorder and to assess their detection rates in the Canadian primary care setting. METHOD: The descriptive, cross-sectional study was conducted in 7 primary care clinics in 3 Canadian provinces, Ontario, British Columbia, and Nova Scotia, from December 6, 2005, to May 5, 2006. Patients in clinic waiting rooms who consented to participate in the study were administered the Mini International Neuropsychiatric Interview (MINI) (N = 840). These patients' medical charts were then reviewed for evidence of previous diagnosis of a mood or anxiety disorder. Misdiagnosis was defined as cases for which a diagnosis was reached on the MINI but not in the patient's chart. RESULTS: Of the 840 primary care patients assessed, 27.2%, 11.4%, 12.6%, 31.2%, and 16.5% of patients met criteria for major depressive disorder, bipolar disorder, panic disorder, generalized anxiety disorder, and social anxiety disorder, respectively. Misdiagnosis rates reached 65.9% for major depressive disorder, 92.7% for bipolar disorder, 85.8% for panic disorder, 71.0% for generalized anxiety disorder, and 97.8% for social anxiety disorder. CONCLUSIONS: With high prevalence rates and poor detection, there is an obvious need to enhance diagnostic screening in the primary care setting. PMID- 21977355 TI - Impact of physician counseling and perception of teratogenic risks: a survey of 96 nonpregnant women with anxiety. AB - OBJECTIVE: To examine the impact of physician counseling on perceived risks, benefits, and likelihood of use of anxiolytic pharmacotherapy during pregnancy among women with a history of anxiety. METHOD: We surveyed 96 nonpregnant women, aged 21-45 years, with panic disorder and/or generalized anxiety disorder (DSM-IV criteria) recruited by their family physicians to participate in an anxiety treatment trial from 7 primary care practices in Pittsburgh, Pennsylvania. Trained research assistants telephoned study participants to assess sociodemographics, psychiatric history, comorbidities, and anxiety severity. Respondents were asked to assess risks, benefits, and likelihood of taking a prescribed anxiolytic during pregnancy using 3 Likert scales at baseline. Respondents were then asked to indicate whether their perceptions would change with (1) a US Food and Drug Administration (FDA) warning reporting a 5% chance of birth defects with use and (2) physician counseling that the medication was safe during pregnancy despite the warning. Data were collected from January 1, 2005, through December 30, 2007. RESULTS: In this study, 46% (44/96) of respondents had generalized anxiety disorder, 14% (14/96) had panic disorder, and 40% (38/96) had both generalized anxiety disorder and panic disorder. The mean baseline Hamilton Anxiety Rating Scale score was 25.6 (SD = 8.4). Respondents were less likely to perceive risk if counseled by their primary care physicians that medication use was safe despite FDA warning. They also saw more benefit in use and reported being more likely to take anxiolytic medications during pregnancy if counseled that doing so was safe. Age, ethnicity, and severity of anxiety did not modify the effect of physician counseling. However, college educated women were less likely to be reassured by primary care physician counseling (P = .05) that anxiolytic use during pregnancy was safe. CONCLUSIONS: Women with anxiety disorders are often hesitant to use anxiolytic medications during pregnancy. Physician counseling may change some women's perceptions of risk and decisions regarding use during pregnancy. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00158327. PMID- 21977356 TI - Cost of illness and comorbidities in adults diagnosed with attention deficit/hyperactivity disorder: a retrospective analysis. AB - OBJECTIVE: This retrospective study assessed the cost of illness and medical and psychiatric comorbidities in adults with attention-deficit/hyperactivity disorder (ADHD) compared with adults without ADHD (matched 1:3) and adults with depression (1:1). Individuals with depression were included as a benchmark against which the burden of ADHD could be measured. METHOD: Measures of health care and employment related costs were compared to generate estimates of medical expenditures, workplace absences, and comorbidities in adults with ADHD (using ICD-9-CM codes) who were enrolled in employer-sponsored health plans throughout 2006. Individuals with ADHD (31,752) were matched with 95,256 non-ADHD controls. The majority of individuals with ADHD (n = 29,965) were also matched with an equal number of individuals with a depression diagnosis (using ICD-9-CM codes). RESULTS: In this adult population with ADHD enrolled in an employer-sponsored health plan, medical and psychiatric comorbidities were the primary drivers of health care utilization and cost. Of note, depression was significantly prevalent among those with ADHD compared to matched non-ADHD controls (14% vs 3.2%; P <= .0001). Subgroup analysis demonstrated that ADHD patients with depression had a significantly higher number of medical and other psychiatric comorbid illnesses including diabetes, hypertension, asthma, irritable bowel syndrome, bipolar disorder, anxiety, alcohol abuse, and substance abuse compared to those with ADHD alone (P <= .0001). Patients with ADHD incurred higher total annual health care expenditures than control subjects ($4,306 vs $2,418); approximately 15% of costs were paid by the patient. The total annual costs associated with productivity losses were also higher (driven by differences in short-term disability costs) in the ADHD group compared with controls ($4,403 vs $4,209). CONCLUSIONS: Medical and psychiatric comorbidities were primary drivers of the direct health care cost associated with ADHD in adult patients. The present study demonstrated that the total costs of ADHD among adults are doubled when indirect costs associated with workplace productivity losses are included. PMID- 21977357 TI - Risk of injury associated with attention-deficit/hyperactivity disorder in adults enrolled in employer-sponsored health plans: a retrospective analysis. AB - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is linked to an increased risk of injury in children. This retrospective analysis evaluated the risk and type of injury associated with ADHD in adults. METHOD: Data were taken from the MarketScan databases, which provide details of health care claims and productivity data for individuals and their dependents with access to employer sponsored health plans. Adults (aged 18-64 years) with >= 2 ADHD-related diagnostic claims (using ICD-9-CM codes) between 2002 and 2007 and evidence of ADHD treatment in 2006 (n = 31,752) were matched to controls without ADHD (1:3; n = 95,256) or individuals with a depression diagnosis (using ICD-9-CM codes; 1:1; n = 29,965). Injury claims were compared between cohorts, and multivariate analyses controlled for differences that remained after matching. RESULTS: Injury claims were more common in individuals with ADHD than in non-ADHD controls (21.5% vs 15.7%; P< .0001) or individuals with depression (21.4% vs 20.5%; P= .008). Multivariate analyses indicated that the relative risk of injury claims was higher in individuals with ADHD than in the non-ADHD control (odds ratio [OR] = 1.32; 95% CI, 1.27-1.37; P< .01) and depression (OR = 1.13; 95% CI, 1.07-1.18; P< .01) groups. Injury claims increased total direct health care expenditure; total expenditures for ADHD patients with injuries were $6,482 compared with $3,722 for ADHD patients without injuries (P < .0001). Comparison of injury-related costs were similar between ADHD patients and non-ADHD controls ($1,109 vs $1,041, respectively), but higher for depression patients than for ADHD patients ($1,792 vs $1,084; P < .01). Injury claim was also associated with increased short-term disability expenditures, as ADHD patients with injury incurred higher mean cost than those without injury ($1,303 vs $620; P = .0001), but lower than those with injury in the depression cohort (vs $2,152; P = .0099) CONCLUSIONS: Adults with ADHD were more likely to incur injury claims than non-ADHD controls or adults with depression in this sample selected on the basis of claims data rather than clinical referrals. Most injuries were relatively minor; however, individuals with injuries incurred higher total direct health care costs than those without injuries. Furthermore, the ratio of indirect costs due to workplace absence to direct health care costs was higher for adults with ADHD than for adults with depression, demonstrating not only the impact of ADHD in the workplace, but also the importance of accounting for productivity data in calculating the true economic burden of ADHD in adults. PMID- 21977358 TI - Metabolic syndrome in obese patients with binge-eating disorder in primary care clinics: a cross-sectional study. AB - BACKGROUND: The distribution and nature of metabolic syndrome in obese patients with binge-eating disorder (BED) are largely unknown and require investigation, particularly in general internal medicine settings. The objectives of this study were to (1) examine the frequency of metabolic syndrome and (2) explore its eating- and weight-related correlates in obese patients with BED. METHOD: This was a cross-sectional analysis of 81 consecutive treatment-seeking obese (body mass index >= 30 kg/m(2)) patients (21 men, 60 women) who met DSM-IV-TR research criteria for BED (either subthreshold criteria: >= 1 binge weekly, n = 19 or full criteria: >= 2 binges weekly, n = 62). Participants were from 2 primary care facilities in a large university-based medical center in an urban setting. Patients with and without metabolic syndrome were compared on demographic features and current and historical eating- and weight-related variables. Data were collected from December 2007 through March 2009. RESULTS: Forty-three percent of patients met criteria for metabolic syndrome. A significantly higher proportion of men (66%) than women (35%) met criteria for metabolic syndrome (P = .012). Patients with versus without metabolic syndrome did not differ significantly in ethnicity or body mass index. Patients with versus without metabolic syndrome did not differ significantly in binge-eating frequency, severity of eating disorder psychopathology, or depression. Analyses of covariance controlling for gender revealed that patients without metabolic syndrome started dieting at a significantly younger age (P = .037), spent more of their adult lives dieting (P = .017), and reported more current dietary restriction (P = .018) than patients with metabolic syndrome. CONCLUSIONS: Metabolic syndrome is common in obese patients with BED in primary care settings and is associated with fewer dieting behaviors. These findings suggest that certain lifestyle behaviors, such as increased dietary restriction, may be potential targets for intervention with metabolic syndrome. PMID- 21977360 TI - Primary care perspectives on treating bipolar disorder: a cross-sectional survey. AB - OBJECTIVE: In this study, we explored the comfort level of and influences upon primary care clinicians in prescribing psychotropic medications to patients with bipolar disorder. METHOD: In May 2010, we mailed a 1-page survey to a cross sectional sample of 143 primary care clinicians in 2 large practice groups asking physicians to specify whether they prescribe psychotropic medications to bipolar patients, describe their comfort level in prescribing psychotropic medications to this patient group, indicate possible influences on their willingness to prescribe psychotropics for bipolar patients, and provide their opinion on whether or not primary care physicians should prescribe these medications to bipolar patients. RESULTS: Of the 38 respondents (response rate of 26.6%), nearly two-thirds (n = 24) reported the prescription of psychotropic medications to bipolar patients in their practices. For questions related to bipolar diagnosis and treatment, the means of all responses trended toward uncomfortable, with the prescription of antipsychotics being indicated as the aspect with which respondents were least comfortable. As for factors influencing a decision to prescribe, the restricted availability of mental health services was rated as most influential. With regard to the perceived role of primary care clinicians in prescribing psychotropic medications to bipolar patients, no respondent indicated that primary care physicians should "always" prescribe, whereas approximately two thirds indicated "rarely" or "on occasion." CONCLUSIONS: While a majority of primary care clinicians prescribe psychotropic medications to patients with bipolar disorder, a majority are also understandably hesitant to do so and appear to do so in particular circumstances, most likely related to the restricted availability of mental health services. PMID- 21977359 TI - Prevalence and treatment of depression in children and adolescents with sickle cell disease: a retrospective cohort study. AB - OBJECTIVE: To describe the prevalence and treatment of comorbid depressive disorders in children and adolescents diagnosed with sickle cell disease. METHOD: A retrospective cohort design evaluating South Carolina Medicaid medical and pharmacy claims between January 1, 1996, and December 31, 2006, was employed to identify 2,194 children and adolescents aged 17 years and younger diagnosed with sickle cell disease. Cohorts diagnosed with and without comorbid unipolar depressive disorders (using DSM-IV-TR criteria) were then compared. RESULTS: Forty-six percent of the sickle cell disease cohort was diagnosed with a depressive disorder (n = 1,017), either dysthymia (90%) or major depressive disorder (10%). Dysthymia was diagnosed at approximately 9 years of age, whereas major depressive disorder was diagnosed at approximately 14 years of age. Compared with the controls, the sickle cell disease cohort with depression had more acute vaso-occlusive pain and acute chest syndrome visits per year, developed more complications with related organ damage, and incurred significantly higher outpatient, acute (emergency + inpatient), and total sickle cell disease care costs. The depression cohort was primarily treated with selective serotonin reuptake inhibitors (SSRIs; 12%) or serotonin-norepinephrine reuptake inhibitors (SNRIs; 10%) for approximately 9 months. Although alleviating the comorbid depression might positively affect their sickle cell disease pain, over 80% of the patients received no antidepressant medications, and many of the prescribed SSRIs and SNRIs have previously shown no impact on relieving chronic pain. CONCLUSIONS: Comorbid depression in sickle cell disease is associated with adverse course and outcomes. These findings underscore the need for earlier and more aggressive treatment of comorbid depression by primary care or psychiatric providers in order to reduce the chronic, severe pain-depression burden on these patients. PMID- 21977361 TI - Why does mommy forget? PMID- 21977362 TI - Old age and loneliness. PMID- 21977363 TI - A case of acute renal failure in a patient recently treated with clozapine and a review of previously reported cases. AB - Clozapine has been reported to cause acute renal failure due to acute interstitial nephritis. We discuss a case of clozapine-induced acute renal failure and compare it to 7 other cases reported in the literature. We review the signs and symptoms of the hypersensitivity response, such as fever and eosinophilia, caused by clozapine and make recommendations for early detection. Early detection and prompt discontinuation of clozapine can prevent renal damage, as can the avoidance of other nephrotoxic drugs like antibiotics. PMID- 21977364 TI - Association of attention-deficit/hyperactivity disorder and celiac disease: a brief report. AB - OBJECTIVE: A possible association of celiac disease with psychiatric and psychological disturbances such as attention-deficit/hyperactivity disorder (ADHD) has been reported repeatedly. The objective of this study was to observe whether a gluten-free diet could alleviate the behavioral symptoms in patients with celiac disease and ADHD. METHOD: Sixty-seven subjects aged 7 to 42 years (mean = 11.4 years) with ADHD were enrolled in the study in South Tyrol, Italy, from 2004 to 2008. Hypescheme, an operational criteria checklist that incorporates DSM-IV and ICD-10 criteria, was used to assess ADHD-like symptomatology. Additionally, blood serum levels of all subjects were assessed for possible celiac disease by examining antigliadine and antiendomysium antibodies. A gluten-free diet was initiated for at least 6 months in celiac disease-positive patients with ADHD. RESULTS: Of the 67 patients with ADHD, 10 were positive for celiac disease. After initiation of the gluten-free diet, patients or their parents reported a significant improvement in their behavior and functioning compared to the period before celiac diagnosis and treatment, which was evident in the overall mean score on the Hypescheme questionnaire (t = 4.22, P = .023). CONCLUSIONS: Celiac disease is markedly overrepresented among patients presenting with ADHD. A gluten-free diet significantly improved ADHD symptoms in patients with celiac disease in this study. The results further suggest that celiac disease should be included in the ADHD symptom checklist. PMID- 21977365 TI - Late-onset cinephilia and compulsive behaviors: harbingers of frontotemporal dementia. PMID- 21977366 TI - Aripiprazole-induced parkinsonism in a child: a case report. PMID- 21977367 TI - The prevalence of borderline personality disorder in a consecutive sample of cardiac stress test patients. PMID- 21977368 TI - Rapid response of disabling tardive dyskinesia to amantadine: a case report. PMID- 21977369 TI - Treatment strategies for bipolar disorder: CALM SEA. PMID- 21977370 TI - Citalopram-induced seizures in a healthy adult taking an FDA-approved dosage: a case report. PMID- 21977371 TI - High-dose zolpidem withdrawal seizure in a patient with spinocerebellar ataxia. PMID- 21977372 TI - Treatment with phytoestrogens for depressive symptoms in late-onset schizophrenia:a case report. PMID- 21977373 TI - Successful treatment with hydroxyzine of acute exacerbation of panic disorder in a healthy man: a case report. PMID- 21977374 TI - A case of obsessive-compulsive disorder presenting as dissociative disorder: the role of sodium thiopental interview. PMID- 21977375 TI - Prevalence of metabolic syndrome in a predominantly cuban, psychiatrically ill, and homeless population. AB - OBJECTIVE: This study examined the prevalence of metabolic syndrome among a group of psychiatric outpatients enrolled in a homeless program that is located in a predominantly Hispanic geographic area of South Florida. METHOD: Data for this retrospective, cross-sectional analysis were obtained from a record review of 122 adult patients who received full medical and psychiatric assessments based on DSM IV criteria during participation in our homeless program from January 2009 to May 2009. The primary outcome measure was the presence of metabolic syndrome. RESULTS: The prevalence of metabolic syndrome within this population was 29.5%. Elevated waist circumference (48.5%) and elevated blood pressure (44.3%) were the 2 most frequent risk factors for the syndrome. Mean length of homelessness was 3.93 years, with no significant relationship noted between the presence of metabolic syndrome and duration of homelessness. Ninety-three percent of the subjects had been diagnosed with either schizophrenia or a mood disorder, and 61% had been treated with an atypical antipsychotic for at least 2 months over the preceding year. Our sample was predominantly Hispanic (79.5%), with Cuban Americans comprising 95% of that group. Among Hispanics, the prevalence rate of metabolic syndrome was 28.9%. CONCLUSIONS: Within our sample, homeless individuals compared to the general adult population in the United States seem to be at equal risk for metabolic syndrome. Although other studies have suggested an increased prevalence for metabolic syndrome among Hispanics, the obtained rate for our particular Hispanic sample was consistent with estimated prevalence of non-Hispanic individuals in the United States. Intervention programs rendering services to this population should include routine screening for presence of cardiovascular risk factors constituting metabolic syndrome. PMID- 21977376 TI - The association between Alzheimer's disease symptom severity and caregiver outcomes: a cross-sectional study. AB - OBJECTIVE: To determine the association between Alzheimer's disease (AD) symptom severity and caregiver outcomes. METHOD: This was a database analysis of the Alzheimer's Disease Caregiver Study, a cross-sectional, caregiver-reported study conducted in 2007. Data were collected nationwide via the Internet and in 8 cities: Detroit, Michigan; Knoxville, Tennessee; Los Angeles, California; Miami, Florida; Philadelphia, Pennsylvania; Phoenix, Arizona; St Louis, Missouri; and Washington, DC. Participants were unpaid adult caregivers of AD patients (N = 1,077). Symptom severity was measured using the Revised Memory and Behavioral Problem Checklist (RMBPC). Caregiver outcomes included the Caregiver Burden Scale, diagnosis of anxiety and depression, use of the emergency room, hospitalization, number of physician visits, and missed workdays in the past 6 months. Linear and logistic regression models were developed to assess effects of AD symptom severity on outcomes. Covariates included caregiver and patient characteristics and interactions of AD symptom severity with covariates based on previous analyses. RESULTS: Of the 1,077 respondents, 1,034 had valid RMBPC overall symptom severity scores. AD symptom severity was a significant (P < .01) predictor of all caregiver outcomes except physician visits. Each unit increase in RMBPC severity score corresponded with an increase of 0.328 (95% CI, 0.101 0.554) units in caregiver burden. Each unit increase in severity resulted in increases in physician visits (b = 0.343; 95% CI, 0.052-0.635) and absenteeism (b = 1.722; 95% CI, 0.694-2.749). For each unit increase in RMBPC severity score, caregivers had greater likelihood of emergency room use (odds ratio = 1.506; 95% CI, 1.230-1.845), hospitalization (OR = 1.393; 95% CI, 1.091-1.777), anxiety (OR = 1.506; 95% CI, 1.257-1.805), and depression (OR = 1.811; 95% CI, 1.505-2.179). CONCLUSIONS: AD symptom severity is significantly associated with poorer caregiver outcomes. Therefore, treatments that slow AD symptom progression may be beneficial to caregiver outcomes. PMID- 21977377 TI - Cost of depression among adults in Japan. AB - OBJECTIVE: The aim of this study was to estimate the annual national cost of major depressive disorder among adults 20 years and older in Japan in 2008. METHOD: The analysis used was a top-down costing approach based on national health statistics. From the societal perspective, the costs examined were direct medical costs, depression-related suicide costs, and workplace costs for all members of society. Direct medical costs included both inpatient and outpatient medical costs, while workplace costs included both absenteeism and presenteeism costs. The authors performed 1-way sensitivity analyses to examine the extent to which results were affected by the choice of parameters used in the cost calculation. All costs were expressed in 2008 US dollar terms. RESULTS: The economic burden of depression in Japan was approximately $11 billion, with $1,570 million relating to direct medical costs, $2,542 million to depression-related suicide costs, and $6,912 million to workplace costs. Compared to previously published studies, this study adopted conservative key assumptions; this may have resulted in a conservative estimate of the annual national cost of depression. CONCLUSIONS: Depression imposes a substantial economic burden on Japanese society, which highlights the urgent need for policymakers to allocate resources toward implementing strategies that prevent and manage depression in the Japanese population. PMID- 21977378 TI - The cognitive profile of depressed patients with cirrhosis. AB - OBJECTIVE: To determine whether patients with cirrhosis and depressive symptoms have a different neuropsychological cognitive profile from patients with cirrhosis without depressive symptoms in order to show that cirrhosis may not be the only cause for cognitive decline in patients with cirrhosis. METHOD: Adult outpatients with a diagnosis of cirrhosis based on histologic findings and clinical characteristics, who did not have clinically overt hepatic encephalopathy and who were being treated in the advanced liver disease and liver transplant clinics, were recruited for the study from May 2003 to May 2006. Patients underwent neuropsychological testing and evaluation for depression using the Beck Depression Inventory-II (BDI-II). Age-adjusted standard neuropsychological domain scores were compared between depressed (BDI-II score >= 14) and nondepressed (BDI-II score < 14) patients. RESULTS: Seventy-five subjects were included in the study. The 23 patients with depression were similar to the 52 nondepressed patients in level of education, age, and race; the laboratory parameters of international normalized ratio, bilirubin, creatinine, and albumin concentration; and Model for End-Stage Liver Disease scores. There was a higher percentage of women in the depressed group than in the nondepressed group, with a trend toward significance (52% vs 29%; P = .07). No etiology of liver disease was associated with depression. In linear regression analyses, decreases in cognitive function were associated with higher BDI-II scores for the domains of working memory (P = .026), with a trend toward significance for visual-perception (P = .056). Approximately 7% of the variability in working memory score was predicted using the BDI score. CONCLUSIONS: Depressive symptoms are associated with worsened cognitive function in cirrhosis. PMID- 21977379 TI - Predictors of sustained response to rivastigmine in patients with Alzheimer's disease: a retrospective analysis. AB - OBJECTIVE: The cholinesterase inhibitor rivastigmine is approved for the treatment of mild to moderate Alzheimer's disease. However, it is not possible to predict which individuals will benefit from treatment. This retrospective analysis of an international, 24-week, randomized, double-blind trial aimed to identify the percentage of persons with Alzheimer's disease who have a sustained response with rivastigmine patch, rivastigmine capsules, or placebo; to determine the magnitude of the sustained treatment response; and to investigate baseline patient characteristics predictive of the observed sustained response. METHOD: Patients who improved on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL) at week 16 and maintained at least the week 16 improvement at week 24 were identified as sustained responders. Treatment differences and baseline predictive factors were assessed in patients demonstrating a 1-, 2-, 3-, 4-, or 5-point sustained improvement. The first patient was screened in November 2003 and the last patient completed the study in January 2006. RESULTS: More persons with Alzheimer's disease had sustained improvements on the ADAS-cog and ADCS-ADL with rivastigmine versus placebo. Sustained improvements of 4 or 5 points on the ADAS-cog or ADCS-ADL were demonstrated in the 9.5-mg/24-h rivastigmine patch (24% and 36% of patients, respectively) and 12-mg/d capsule groups (28% on both outcome measures). Factors predictive of a sustained response to treatment included baseline Mini-Mental State Examination, ADAS-cog, and ADCS-ADL scores and treatment, country of treatment, and time since first symptom was diagnosed by a physician. CONCLUSIONS: Understanding factors predictive of sustained cholinesterase inhibitor treatment response should help to optimize Alzheimer's disease management and encourage compliance by allowing more realistic expectations of treatment effects. PMID- 21977380 TI - Responses to the medical review of systems: borderline versus nonborderline patients in an internal medicine outpatient clinic. AB - OBJECTIVE: In both clinical and empirical reports, individuals with borderline personality disorder have been characterized by tendencies toward somatization. In this study, we examined the relationship between somatic symptoms, in the context of a traditional medical review of systems, and borderline personality disorder, using 2 self-report measures for this Axis II dysfunction. METHOD: In a cross-sectional consecutive sample of 381 internal medicine outpatients being seen predominantly by resident providers in a midsized, midwestern city in October 2010, we assessed 35 physical symptoms, which constitute 1 version of a medical review of systems, and borderline personality disorder using the Borderline Personality Disorder Scale of the Personality Diagnostic Questionnaire 4 (PDQ-4) and the Self-Harm Inventory (SHI). RESULTS: The total number of symptoms endorsed on the medical review of systems was positively correlated with scores on the PDQ-4 (r = 0.42, P < .001, n = 369) and scores on the SHI (r = 0.36, P < .001, n = 366). In addition, the percentages of participants with borderline personality disorder increased as the number of endorsed symptoms increased. No individual symptom, or symptom pattern, was particularly related to participants with borderline personality disorder features. CONCLUSIONS: In an internal medicine outpatient sample from a resident provider clinic, patients with borderline personality disorder characteristics endorsed significantly more physical symptoms on a medical review of systems than those without such characteristics, suggesting a somatic overlay in individuals with this Axis II disorder. No specific physical symptom pattern or cluster was evident among those with these Axis II features. PMID- 21977381 TI - When is it dementia? PMID- 21977382 TI - Rehabilitation. PMID- 21977383 TI - Fibro-osseous Lesions of the Jaw: A Report of Two Cases. AB - Fibro-osseous lesions of the maxillofacial bones comprise a diverse group of pathologic conditions that include developmental lesions, reactive or dysplastic diseases, and neoplasms. The concept of fibro-osseous lesions has evolved over the last several decades and now includes two major entities: fibrous dysplasia and ossifying fibroma. The less common lesions include florid osseous dysplasia, periapical dysplasia, focal sclerosing osteomyelitis, proliferative periostitis of Garre, and osteitis deformans. We report two cases, the first, a craniofacial polyostotic fibrous dysplasia, and the second, a juvenile ossifying fibroma of maxilla. PMID- 21977384 TI - Acute Renal Artery Occlusion with Prolonged Renal Ischemia: A Case of Successful Treatment with Stent Placement and Catheter-directed Thrombolysis. AB - We present a case of acute renal artery occlusion caused by a high-grade stenosis associated with in-situ thrombosis. Endovascular renal artery stent placement combined with catheter-directed thrombolysis reversed the renal ischemia with restoration of renal function despite the prolonged ischemia. PMID- 21977385 TI - Pilomatrixoma of the adult male breast: a rare tumor with typical ultrasound features. AB - Pilomatrixomas are uncommon benign skin neoplasms arising from the hair follicle matrix. They occur more commonly in children than adults. Most originate on the head, neck, or upper extremities, less commonly on the trunk or lower extremities, and very infrequently in the breast. We present a rare case of pilomatrixoma of the breast in an adult male. As the patient had a strong family history of breast cancer, a full work-up of the breast mass was performed. Ultimately, an excisional biopsy was carried out for patient reassurance. PMID- 21977386 TI - Sprengel deformity: magnetic resonance imaging findings in two pediatric cases. AB - The characteristics of Sprengel deformity, which is also called congenital high scapula, are malposition and dysplasia of the affected scapula, with possible omovertebral connection. The aim of the present study was mainly to present the magnetic resonance imaging (MRI) findings of two pediatric cases of Sprengel deformity. A 7-year-old girl and a 9-year-old boy with deformities in their right shoulder were studied. Plain radiographs were obtained. MRI was performed for both children. The fibrous omovertebral connection is depicted in its longest form in one plane. Omovertebral band is best screened in coronal and axial cross sections. We are introducing a new MRI sign which we named as "Ra's eye" to define the appearance of omovertebral band within the surrounding fat tissue. PMID- 21977387 TI - Pseudoaneurysm of uterine artery: a rare cause of secondary postpartum hemorrhage, managed with uterine artery embolisation. AB - Uterine artery pseudoaneurysm is a rare cause of secondary postpartum hemorrhage but is potentially life-threatening and can occur after caesarean section (c section) or a hysterectomy. A 28-year-old woman who developed secondary postpartum hemorrhage after c-section was diagnosed to have pseudoaneurysm from the left uterine artery on ultrasound (US) and computed tomography (CT) scan. She was treated with coiling of the pseudoaneurysm with stainless steel coil via selective catheterization of the uterine artery. The procedure was uneventful and the pseudoaneurysm was successfully obliterated. Angiographic embolization is a safe and effective method for treating postpartum hemorrhage due to pseudoaneurysm in hemodynamically stable patients. Therefore, it should be considered as a treatment option before resorting to surgery, in appropriately selected cases. PMID- 21977388 TI - Magnetic resonance imaging of neurosarcoidosis. AB - Neurosarcoidosis is an uncommon condition with protean manifestations. Magnetic resonance imaging (MRI) is often used in the diagnostic evaluation and follow-up of patients with neurosarcoidosis. Therefore, familiarity with the variety of MRI appearances is important. In this pictorial essay, the range of possible patterns of involvement in neurosarcoidosis are depicted and discussed. These include intracranial and spine leptomeningeal involvement, cortical and cerebral white matter lesions, corpus callosum involvement, sellar and suprasellar involvement, periventricular involvement, cranial nerve involvement, cavernous sinus involvement, hydrocephalus, dural involvement, ischemic lesions, perivascular involvement, orbit lesions, osseous involvement, nerve root involvement, and spinal cord intramedullary involvement. Differential diagnoses for each pattern of involvement of neurosarcoidosis are also provided. PMID- 21977389 TI - Angiogenesis imaging in neoplasia. AB - Angiogenesis plays a key role in physiological and pathophysiological processes and is recognized as being essential for tumor growth and metastases. The recent oncological development of anti-angiogenic drugs brings with it a need for angiogenesis quantification and monitoring of response. The nature of these agents means that traditional anatomical methods of assessing morphologic change are outmoded and functional imaging techniques and/or agents are necessary. Herein, we describe the various imaging techniques that can be employed to assess angiogenesis, along with their inherent advantages and disadvantages and discuss the current and future developments in the field. PMID- 21977390 TI - Sensing surface PEGylation with microcantilevers. AB - Polymers are often used to modify surface properties to control interfacial processes. Their sensitivity to solvent conditions and ability to undergo conformational transitions makes polymers attractive in tailoring surface properties with specific functionalities leading to applications in diverse areas ranging from tribology to colloidal stability and medicine. A key example is polyethylene glycol (PEG), which is widely used as a protein-resistant coating given its low toxicity and biocompatibility. We report here a microcantilever based sensor for the in situ characterization of PEG monolayer formation on Au using the "grafting to" approach. Moreover, we demonstrate how microcantilevers can be used to monitor conformational changes in the grafted PEG layer in different solvent conditions. This is supported by atomic force microscope (AFM) images and force-distance curve measurements of the microcantilever chip surface, which show that the grafted PEG undergoes a reversible collapse when switching between good and poor solvent conditions, respectively. PMID- 21977391 TI - Enhanced visible light photocatalysis through fast crystallization of zinc oxide nanorods. AB - Hydrothermally grown ZnO nanorods have inherent crystalline defects primarily due to oxygen vacancies that enhance optical absorption in the visible spectrum, opening up possibilities for visible light photocatalysis. Comparison of photocatalytic activity of ZnO nanorods and nanoparticle films on a test contaminant methylene blue with visible light irradiation at 72 kilolux (klx) showed that ZnO nanorods are 12-24% more active than ZnO nanoparticulate films. This can be directly attributed to the increased effective surface area for adsorption of target contaminant molecules. Defects, in the form of interstitials and vacancies, were intentionally created by faster growth of the nanorods by microwave activation. Visible light photocatalytic activity was observed to improve by ~8% attributed to the availability of more electron deficient sites on the nanorod surfaces. Engineered defect creation in nanostructured photocatalysts could be an attractive solution for visible light photocatalysis. PMID- 21977393 TI - Uniform excitations in magnetic nanoparticles. AB - We present a short review of the magnetic excitations in nanoparticles below the superparamagnetic blocking temperature. In this temperature regime, the magnetic dynamics in nanoparticles is dominated by uniform excitations, and this leads to a linear temperature dependence of the magnetization and the magnetic hyperfine field, in contrast to the Bloch T(3/2) law in bulk materials. The temperature dependence of the average magnetization is conveniently studied by Mossbauer spectroscopy. The energy of the uniform excitations of magnetic nanoparticles can be studied by inelastic neutron scattering. PMID- 21977392 TI - Preparation and characterization of supported magnetic nanoparticles prepared by reverse micelles. AB - Monatomic (Fe, Co) and bimetallic (FePt and CoPt) nanoparticles were prepared by exploiting the self-organization of precursor loaded reverse micelles. Achievements and limitations of the preparation approach are critically discussed. We show that self-assembled metallic nanoparticles can be prepared with diameters d = 2-12 nm and interparticle distances D = 20-140 nm on various substrates. Structural, electronic and magnetic properties of the particle arrays were characterized by several techniques to give a comprehensive view of the high quality of the method. For Co nanoparticles, it is demonstrated that magnetostatic interactions can be neglected for distances which are at least 6 times larger than the particle diameter. Focus is placed on FePt alloy nanoparticles which show a huge magnetic anisotropy in the L1(0) phase, however, this is still less by a factor of 3-4 when compared to the anisotropy of the bulk counterpart. A similar observation was also found for CoPt nanoparticles (NPs). These results are related to imperfect crystal structures as revealed by HRTEM as well as to compositional distributions of the prepared particles. Interestingly, the results demonstrate that the averaged effective magnetic anisotropy of FePt nanoparticles does not strongly depend on size. Consequently, magnetization stability should scale linearly with the volume of the NPs and give rise to a critical value for stability at ambient temperature. Indeed, for diameters above 6 nm such stability is observed for the current FePt and CoPt NPs. Finally, the long-term conservation of nanoparticles by Au photoseeding is presented. PMID- 21977394 TI - Flash laser annealing for controlling size and shape of magnetic alloy nanoparticles. AB - We propose an original route to prepare magnetic alloy nanoparticles with uniform size and shape by using nanosecond annealing under pulsed laser irradiation. As demonstrated here on CoPt nanoparticles, flash laser annealing gives an unprecedented opportunity to control the size and the shape of bimetallic nanoparticles without changing their composition. The mechanisms involved in the complete reshaping of the nanoparticle thin films are discussed and it is also shown that order-disorder phase transformations occur under laser irradiation. This technique is then very interesting for magnetic alloy nanoparticles studies and applications because it opens up a new way to fabricate size-controlled spherical nanoparticles with narrow size dispersion. PMID- 21977396 TI - Aerosol assisted fabrication of two dimensional ZnO island arrays and honeycomb patterns with identical lattice structures. AB - Two dimensional island arrays and honeycomb patterns consisting of ZnO nanocrystal clusters were fabricated on predefined TiO(2) seed patterns prepared by vacuum free, aerosol assisted wet-chemical synthesis. The TiO(2) seed patterns were prepared by applying an aerosol of a water soluble titanium complex on hexagonally close-packed polystyrene bead arrays for different lengths of time. Scanning electron microscopy revealed that a dot array grows into a honeycomb shape as increasing amounts of the precursor were deposited. ZnO nucleation on substrates with a dot array and honeycomb patterns resulted in the formation of two discrete patterns with contrasting fill fractions of the materials. PMID- 21977395 TI - On the reticular construction concept of covalent organic frameworks. AB - The concept of reticular chemistry is investigated to explore the applicability of the formation of Covalent Organic Frameworks (COFs) from their defined individual building blocks. Thus, we have designed, optimized and investigated a set of reported and hypothetical 2D COFs using Density Functional Theory (DFT) and the related Density Functional based tight-binding (DFTB) method. Linear, trigonal and hexagonal building blocks have been selected for designing hexagonal COF layers. High-symmetry AA and AB stackings are considered, as well as low symmetry serrated and inclined stackings of the layers. The latter ones are only slightly modified compared to the high-symmetry forms, but show higher energetic stability. Experimental XRD patterns found in literature also support stackings with highest formation energies. All stacking forms vary in their interlayer separations and band gaps; however, their electronic densities of states (DOS) are similar and not significantly different from that of a monolayer. The band gaps are found to be in the range of 1.7-4.0 eV. COFs built of building blocks with a greater number of aromatic rings have smaller band gaps. PMID- 21977397 TI - Review and outlook: from single nanoparticles to self-assembled monolayers and granular GMR sensors. AB - This paper highlights recent advances in synthesis, self-assembly and sensing applications of monodisperse magnetic Co and Co-alloyed nanoparticles. A brief introduction to solution phase synthesis techniques as well as the magnetic properties and aspects of the self-assembly process of nanoparticles will be given with the emphasis placed on selected applications, before recent developments of particles in sensor devices are outlined. Here, the paper focuses on the fabrication of granular magnetoresistive sensors by the employment of particles themselves as sensing layers. The role of interparticle interactions is discussed. PMID- 21977398 TI - Fabrication and spectroscopic studies on highly luminescent CdSe/CdS nanorod polymer composites. AB - Highly luminescent nanocomposites were prepared by incorporating CdSe/CdS core/shell nanorods into different polymer matrices. The resulting nanocomposites show high transparency of up to 93%. A photoluminescence quantum efficiency of 70% was obtained, with an optimum combination of nanorod (0.05 wt %) and at a UV initiator concentration of 0.1 wt % for poly(lauryl methacrylate). Nanorods tend to agglomerate in cellulose triacetate. PMID- 21977399 TI - Magnetic coupling mechanisms in particle/thin film composite systems. AB - Magnetic gamma-Fe(2)O(3) nanoparticles with a mean diameter of 20 nm and size distribution of 7% were chemically synthesized and spin-coated on top of a Si substrate. As a result, the particles self-assembled into a monolayer with hexagonal close-packed order. Subsequently, the nanoparticle array was coated with a Co layer of 20 nm thickness. The magnetic properties of this composite nanoparticle/thin film system were investigated by magnetometry and related to high-resolution transmission electron microscopy studies. Herein three systems were compared: i.e. a reference sample with only the particle monolayer, a composite system where the particle array was ion-milled prior to the deposition of a thin Co film on top, and a similar composite system but without ion-milling. The nanoparticle array showed a collective super-spin behavior due to dipolar interparticle coupling. In the composite system, we observed a decoupling into two nanoparticle subsystems. In the ion-milled system, the nanoparticle layer served as a magnetic flux guide as observed by magnetic force microscopy. Moreover, an exchange bias effect was found, which is likely to be due to oxygen exchange between the iron oxide and the Co layer, and thus forming of an antiferromagnetic CoO layer at the gamma-Fe(2)O(3)/Co interface. PMID- 21977401 TI - Precursor concentration and temperature controlled formation of polyvinyl alcohol capped CdSe-quantum dots. AB - Polyvinyl alcohol-capped CdSe quantum dots, with a size within their quantum confinement limit, were prepared in aqueous solution at room temperature, by a simple and environmentally friendly chemical method. The size of the CdSe quantum dots was found to be dependent on the concentrations of the precursors of cadmium and selenium ions, as well as on the aging time and the reaction temperature; all of which could be used conveniently for tuning the size of the particles, as well as their optical properties. The synthesized quantum dots were characterized by optical absorption spectroscopy, fluorescence spectroscopy, X-ray diffraction, atomic force microscopy and transmission electron microscopy. The samples were fluorescent at room temperature; the green fluorescence was assigned to band edge emission, and the near-infrared fluorescence peaks at about 665 and 865 nm were assigned to shallow and deep trap states emissions, respectively. The quantum dots were fairly stable up to several days. PMID- 21977400 TI - Ultrafine metallic Fe nanoparticles: synthesis, structure and magnetism. AB - The results of the investigation of the structural and magnetic (static and dynamic) properties of an assembly of metallic Fe nanoparticles synthesized by an organometallic chemical method are described. These nanoparticles are embedded in a polymer, monodisperse, with a diameter below 2 nm, which corresponds to a number of around 200 atoms. The X-ray absorption near-edge structure and Mossbauer spectrum are characteristic of metallic Fe. The structural studies by wide angle X-ray scattering indicate an original polytetrahedral atomic arrangement similar to that of beta-Mn, characterized by a short-range order. The average magnetic moment per Fe atom is raised to 2.59 u(B) (for comparison, bulk value of metallic Fe: 2.2 u(B)). Even if the spontaneous magnetization decreases rapidly as compared to bulk materials, it remains enhanced even up to room temperature. The gyromagnetic ratio measured by ferromagnetic resonance is of the same order as that of bulk Fe, which allows us to conclude that the orbital and spin contributions increase at the same rate. A large magnetic anisotropy for metallic Fe has been measured up to (3.7 +/- 1.0).10(5) J/m(3). Precise analysis of the low temperature Mossbauer spectra, show a broad distribution of large hyperfine fields. The largest hyperfine fields display the largest isomer shifts. This indicates a progressive increase of the magnetic moment inside the particle from the core to the outer shell. The components corresponding to the large hyperfine fields with large isomer shifts are indeed characteristic of surface atoms. PMID- 21977402 TI - Low-temperature solution growth of ZnO nanotube arrays. AB - Single crystal ZnO nanotube arrays were synthesized at low temperature in an aqueous solution containing zinc nitrate and hexamethylenetetramine. It was found that the pH value of the reaction solution played an important role in mediating the growth of ZnO nanostructures. A change in the growth temperature might change the pH value of the solution and bring about the structure conversion of ZnO from nanorods to nanotubes. It was proposed that the ZnO nanorods were initially formed while the reaction solution was at a relatively high temperature (~90 degrees C) and therefore enriched with colloidal Zn(OH)(2), which allowed a fast growth of ZnO nanocrystals along the [001] orientation to form nanorods. A decrease in the reaction temperature yielded a supersaturated solution, resulting in an increase in the concentration of OH(-) ions as well as the pH value of the solution. Colloidal Zn(OH)(2) in the supersaturated solution trended to precipitate. However, because of a slow diffusion process in view of the low temperature and low concentration of the colloidal Zn(OH)(2), the growth of the (001) plane of ZnO nanorods was limited and only occurred at the edge of the nanorods, eventually leading to the formation of a nanotube shape. In addition, it was demonstrated that the pH might impact the surface energy difference between the polar and non-polar faces of the ZnO crystal. Such a surface energy difference became small at high pH and hereby the prioritized growth of ZnO crystal along the [001] orientation was suppressed, facilitating the formation of nanotubes. This paper demonstrates a new strategy for the fabrication of ZnO nanotubes on a large scale and presents a more comprehensive understanding of the growth of tube-shaped ZnO in aqueous solution at low temperature. PMID- 21977403 TI - Electrochemical behavior of dye-linked L-proline dehydrogenase on glassy carbon electrodes modified by multi-walled carbon nanotubes. AB - A glassy carbon electrode (GC) was modified by multi-walled carbon nanotubes (MWCNTs). The modified electrode showed a pair of redox peaks that resulted from the oxygen-containing functional groups on the nanotube surface. A recombinant thermostable dye-linked L-proline dehydrogenase (L-proDH) from hyperthermophilic archaeon (Thermococcus profundus) was further immobilized by physical adsorption. The modified electrode (GC/MWCNTs/L-proDH) exhibited an electrocatalytic signal for L-proline compared to bare GC, GC/L-proDH and GC/MWCNTs electrodes, which suggested that the presence of MWCNTs efficiently enhances electron transfer between the active site of enzyme and electrode surface. The immobilized L-proDH showed a typical Michaelis-Menten catalytic response with lower apparent constant. PMID- 21977404 TI - Magnetic nanoparticles for biomedical NMR-based diagnostics. AB - Rapid and accurate measurements of protein biomarkers, pathogens and cells in biological samples could provide useful information for early disease diagnosis, treatment monitoring, and design of personalized medicine. In general, biological samples have only negligible magnetic susceptibility. Thus, using magnetic nanoparticles for biosensing not only enhances sensitivity but also effectively reduces sample preparation needs. This review focuses on the use of magnetic nanoparticles for in vitro detection of biomolecules and cells based on magnetic resonance effects. This detection platform, termed diagnostic magnetic resonance (DMR), exploits magnetic nanoparticles as proximity sensors, which modulate the spin-spin relaxation time of water molecules surrounding molecularly-targeted nanoparticles. By developing more effective magnetic nanoparticle biosensors, DMR detection limits for various target moieties have been considerably improved over the last few years. Already, a library of magnetic nanoparticles has been developed, in which a wide range of targets, including DNA/mRNA, proteins, small molecules/drugs, bacteria, and tumor cells, have been quantified. More recently, the capabilities of DMR technology have been further advanced with new developments such as miniaturized nuclear magnetic resonance detectors, better magnetic nanoparticles and novel conjugational methods. These developments have enabled parallel and sensitive measurements to be made from small volume samples. Thus, the DMR technology is a highly attractive platform for portable, low-cost, and efficient biomolecular detection within a biomedical setting. PMID- 21977405 TI - Scanning probe microscopy and related methods. PMID- 21977406 TI - A collisional model for AFM manipulation of rigid nanoparticles. AB - The trajectories of differently shaped nanoparticles manipulated by atomic force microscopy are related to the scan path of the probing tip. The direction of motion of the nanoparticles is essentially fixed by the distance b between consecutive scan lines. Well-defined formulas are obtained in the case of rigid nanospheres and nanowires. Numeric results are provided for symmetric nanostars. As a result, orienting the fast scan direction perpendicular to the desired direction of motion and reducing b well below the linear size of the particles turns out to be an efficient way to control the nanomanipulation process. PMID- 21977407 TI - The description of friction of silicon MEMS with surface roughness: virtues and limitations of a stochastic Prandtl-Tomlinson model and the simulation of vibration-induced friction reduction. AB - We have replaced the periodic Prandtl-Tomlinson model with an atomic-scale friction model with a random roughness term describing the surface roughness of micro-electromechanical systems (MEMS) devices with sliding surfaces. This new model is shown to exhibit the same features as previously reported experimental MEMS friction loop data. The correlation function of the surface roughness is shown to play a critical role in the modelling. It is experimentally obtained by probing the sidewall surfaces of a MEMS device flipped upright in on-chip hinges with an AFM (atomic force microscope). The addition of a modulation term to the model allows us to also simulate the effect of vibration-induced friction reduction (normal-force modulation), as a function of both vibration amplitude and frequency. The results obtained agree very well with measurement data reported previously. PMID- 21977408 TI - Tip-sample interactions on graphite studied using the wavelet transform. AB - Wavelet transform analysis is applied to a thermally excited cantilever to get insights into fundamental thermodynamical properties of its motion. The shortcomings of the widely used Fourier analysis are briefly discussed to put into perspective the wavelet transform analysis, used to describe the temporal evolution of the spectral content of the thermal oscillations of a cantilever with an interacting tip. This analysis allows to retrieve the force gradients, the forces and the Hamaker constant in a measurement time of less than 40 ms. PMID- 21977409 TI - Magnetic interactions between nanoparticles. AB - We present a short overview of the influence of inter-particle interactions on the properties of magnetic nanoparticles. Strong magnetic dipole interactions between ferromagnetic or ferrimagnetic particles, that would be superparamagnetic if isolated, can result in a collective state of nanoparticles. This collective state has many similarities to spin-glasses. In samples of aggregated magnetic nanoparticles, exchange interactions are often important and this can also lead to a strong suppression of superparamagnetic relaxation. The temperature dependence of the order parameter in samples of strongly interacting hematite nanoparticles or goethite grains is well described by a simple mean field model. Exchange interactions between nanoparticles with different orientations of the easy axes can also result in a rotation of the sub-lattice magnetization directions. PMID- 21977410 TI - Defects in oxide surfaces studied by atomic force and scanning tunneling microscopy. AB - Surfaces of thin oxide films were investigated by means of a dual mode NC AFM/STM. Apart from imaging the surface termination by NC-AFM with atomic resolution, point defects in magnesium oxide on Ag(001) and line defects in aluminum oxide on NiAl(110), respectively, were thoroughly studied. The contact potential was determined by Kelvin probe force microscopy (KPFM) and the electronic structure by scanning tunneling spectroscopy (STS). On magnesium oxide, different color centers, i.e., F(0), F(+), F(2+) and divacancies, have different effects on the contact potential. These differences enabled classification and unambiguous differentiation by KPFM. True atomic resolution shows the topography at line defects in aluminum oxide. At these domain boundaries, STS and KPFM verify F(2+)-like centers, which have been predicted by density functional theory calculations. Thus, by determining the contact potential and the electronic structure with a spatial resolution in the nanometer range, NC-AFM and STM can be successfully applied on thin oxide films beyond imaging the topography of the surface atoms. PMID- 21977411 TI - Single-pass Kelvin force microscopy and dC/dZ measurements in the intermittent contact: applications to polymer materials. AB - We demonstrate that single-pass Kelvin force microscopy (KFM) and capacitance gradient (dC/dZ) measurements with force gradient detection of tip-sample electrostatic interactions can be performed in the intermittent contact regime in different environments. Such combination provides sensitive detection of the surface potential and capacitance gradient with nanometer-scale spatial resolution as it was verified on self-assemblies of fluoroalkanes and a metal alloy. The KFM and dC/dZ applications to several heterogeneous polymer materials demonstrate the compositional mapping of these samples in dry and humid air as well as in organic vapors. In situ imaging in different environments facilitates recognition of the constituents of multi-component polymer systems due to selective swelling of components. PMID- 21977412 TI - Synthesis of LiNbO(3) nanoparticles in a mesoporous matrix. AB - The synthesis of LiNbO(3) nanoparticles in SBA-15 is reported for the first time. The preparation of nanoparticles was carried out by impregnation from the metal precursor and mesoporous silica SBA-15 as the template. A rapid one-step treatment in an IR furnace reduces the preparation time to only 10 min. In comparison, a conventional furnace requires 5 h reaction time to produce nanoparticles with similar textural properties. Another advantage of applying an IR furnace compared to conventional heating is the extremely high heating rate (up to 10 degrees C/s) and corresponding time saving. The resulting samples were investigated by powder X-ray diffraction, nitrogen physisorption, and high resolution transmission electron microscopy (HRTEM). The obtained nanoparticles are spherical with a diameter of approximately 10 nm. PMID- 21977413 TI - Oriented growth of porphyrin-based molecular wires on ionic crystals analysed by nc-AFM. AB - The growth of molecular assemblies at room temperature on insulating surfaces is one of the main goals in the field of molecular electronics. Recently, the directed growth of porphyrin-based molecular wires on KBr(001) was presented. The molecule-surface interaction associated with a strong dipole moment of the molecules was sufficient to bind them to the surface; while a stabilization of the molecular assemblies was reached due to the intermolecular interaction by pi pi binding. Here, we show that the atomic structure of the substrate can control the direction of the wires and consequently, complex molecular assemblies can be formed. The electronic decoupling of the molecules by one or two monolayers of KBr from the Cu(111) substrate is found to be insufficient to enable comparable growth conditions to bulk ionic materials. PMID- 21977414 TI - Kinetic lattice Monte-Carlo simulations on the ordering kinetics of free and supported FePt L1(0)-nanoparticles. AB - The ordering kinetics in free and supported L1(0) nanoparticles was studied by means of lattice-based kinetic Monte-Carlo simulations. Starting from a fully disordered particle of Wulff shape, the simulations show that the nucleation of ordered domains is starting quickly on various (100) facets but is retarded in the particle volume due to the lack of vacancies compared with a thin film geometry. If a substrate is present, we do not find significant differences in the ordering behavior. This holds true, even if we impose a massively increased thermodynamic driving force for interface segregation, because the nucleation of ordered domains on free facets is significantly faster than the bulk diffusion of the segregating species to the interface. In cases where wetting of the substrate or surface facetting occurs, we find that diffusional atomic motion on the surface goes along with an enhanced long-range order. PMID- 21977415 TI - Structure, morphology, and magnetic properties of Fe nanoparticles deposited onto single-crystalline surfaces. AB - BACKGROUND: Magnetic nanostructures and nanoparticles often show novel magnetic phenomena not known from the respective bulk materials. In the past, several methods to prepare such structures have been developed - ranging from wet chemistry-based to physical-based methods such as self-organization or cluster growth. The preparation method has a significant influence on the resulting properties of the generated nanostructures. Taking chemical approaches, this influence may arise from the chemical environment, reaction kinetics and the preparation route. Taking physical approaches, the thermodynamics and the kinetics of the growth mode or - when depositing preformed clusters/nanoparticles on a surface - the landing kinetics and subsequent relaxation processes have a strong impact and thus need to be considered when attempting to control magnetic and structural properties of supported clusters or nanoparticles. RESULTS: In this contribution we focus on mass-filtered Fe nanoparticles in a size range from 4 nm to 10 nm that are generated in a cluster source and subsequently deposited onto two single crystalline substrates: fcc Ni(111)/W(110) and bcc W(110). We use a combined approach of X-ray magnetic circular dichroism (XMCD), reflection high energy electron diffraction (RHEED) and scanning tunneling microscopy (STM) to shed light on the complex and size-dependent relation between magnetic properties, crystallographic structure, orientation and morphology. In particular XMCD reveals that Fe particles on Ni(111)/W(110) have a significantly lower (higher) magnetic spin (orbital) moment compared to bulk iron. The reduced spin moments are attributed to the random particle orientation being confirmed by RHEED together with a competition of magnetic exchange energy at the interface and magnetic anisotropy energy in the particles. The RHEED data also show that the Fe particles on W(110) - despite of the large lattice mismatch between iron and tungsten - are not strained. Thus, strain is most likely not the origin of the enhanced orbital moments as supposed before. Moreover, RHEED uncovers the existence of a spontaneous process for epitaxial alignment of particles below a critical size of about 4 nm. STM basically confirms the shape conservation of the larger particles but shows first indications for an unexpected reshaping occurring at the onset of self-alignment. CONCLUSION: The magnetic and structural properties of nanoparticles are strongly affected by the deposition kinetics even when soft landing conditions are provided. The orientation of the deposited particles and thus their interface with the substrate strongly depend on the particle size with consequences regarding particularly the magnetic behavior. Spontaneous and epitaxial self-alignment can occur below a certain critical size. This may enable the obtainment of samples with controlled, uniform interfaces and crystallographic orientations even in a random deposition process. However, such a reorientation process might be accompanied by a complex reshaping of the particles. PMID- 21977416 TI - Switching adhesion forces by crossing the metal-insulator transition in Magneli type vanadium oxide crystals. AB - Magneli-type vanadium oxides form the homologous series V(n)O(2) (n) (-1) and exhibit a temperature-induced, reversible metal-insulator first order phase transition (MIT). We studied the change of the adhesion force across the transition temperature between the cleavage planes of various vanadium oxide Magneli phases (n = 3 ... 7) and spherical titanium atomic force microscope (AFM) tips by systematic force-distance measurements with a variable-temperature AFM under ultrahigh vacuum conditions (UHV). The results show, for all investigated samples, that crossing the transition temperatures leads to a distinct change of the adhesion force. Low adhesion corresponds consistently to the metallic state. Accordingly, the ability to modify the electronic structure of the vanadium Magneli phases while maintaining composition, stoichiometry and crystallographic integrity, allows for relating frictional and electronic material properties at the nano scale. This behavior makes the vanadium Magneli phases interesting candidates for technology, e.g., as intelligent devices or coatings where switching of adhesion or friction is desired. PMID- 21977417 TI - Biomimetics inspired surfaces for drag reduction and oleophobicity/philicity. AB - The emerging field of biomimetics allows one to mimic biology or nature to develop nanomaterials, nanodevices, and processes which provide desirable properties. Hierarchical structures with dimensions of features ranging from the macroscale to the nanoscale are extremely common in nature and possess properties of interest. There are a large number of objects including bacteria, plants, land and aquatic animals, and seashells with properties of commercial interest. Certain plant leaves, such as lotus (Nelumbo nucifera) leaves, are known to be superhydrophobic and self-cleaning due to the hierarchical surface roughness and presence of a wax layer. In addition to a self-cleaning effect, these surfaces with a high contact angle and low contact angle hysteresis also exhibit low adhesion and drag reduction for fluid flow. An aquatic animal, such as a shark, is another model from nature for the reduction of drag in fluid flow. The artificial surfaces inspired from the shark skin and lotus leaf have been created, and in this article the influence of structure on drag reduction efficiency is reviewed. Biomimetic-inspired oleophobic surfaces can be used to prevent contamination of the underwater parts of ships by biological and organic contaminants, including oil. The article also reviews the wetting behavior of oil droplets on various superoleophobic surfaces created in the lab. PMID- 21977418 TI - Manipulation of gold colloidal nanoparticles with atomic force microscopy in dynamic mode: influence of particle-substrate chemistry and morphology, and of operating conditions. AB - One key component in the assembly of nanoparticles is their precise positioning to enable the creation of new complex nano-objects. Controlling the nanoscale interactions is crucial for the prediction and understanding of the behaviour of nanoparticles (NPs) during their assembly. In the present work, we have manipulated bare and functionalized gold nanoparticles on flat and patterned silicon and silicon coated substrates with dynamic atomic force microscopy (AFM). Under ambient conditions, the particles adhere to silicon until a critical drive amplitude is reached by oscillations of the probing tip. Beyond that threshold, the particles start to follow different directions, depending on their geometry, size and adhesion to the substrate. Higher and respectively, lower mobility was observed when the gold particles were coated with methyl (-CH(3)) and hydroxyl ( OH) terminated thiol groups. This major result suggests that the adhesion of the particles to the substrate is strongly reduced by the presence of hydrophobic interfaces. The influence of critical parameters on the manipulation was investigated and discussed viz. the shape, size and grafting of the NPs, as well as the surface chemistry and the patterning of the substrate, and finally the operating conditions (temperature, humidity and scan velocity). Whereas the operating conditions and substrate structure are shown to have a strong effect on the mobility of the particles, we did not find any differences when manipulating ordered vs random distributed particles. PMID- 21977419 TI - Twofold role of calcined hydrotalcites in the degradation of methyl parathion pesticide. AB - Methyl parathion (MP) is a very toxic organophosphate pesticide used as a non systematic insecticide and acaricide on many corps. As MP and its by-products are highly toxic, they have to be retained to avoid pollution of rivers and lakes. Highly efficient sorbents are hydrotalcites (HTs) (or anionic clays). We have correlated the degradation of an aqueous solution of MP at room temperature, with the basicity of the adsorbing materials. It was found that the metal composition of hydrotalcites determines both the surface electronic properties (basic or acidic) and the sorption capacity. Depending on the basic strength, some calcined hydrotalcites can catalyze the transformation of MP to p-nitrophenol (p-NP) and retain its by-products. Such a process has the advantage of being able to be carried out at room temperature and at the pH of the pesticide solution. PMID- 21977420 TI - Microfluidic anodization of aluminum films for the fabrication of nanoporous lipid bilayer support structures. AB - Solid state nanoporous membranes show great potential as support structures for biointerfaces. In this paper, we present a technique for fabricating nanoporous alumina membranes under constant-flow conditions in a microfluidic environment. This approach allows the direct integration of the fabrication process into a microfluidic setup for performing biological experiments without the need to transfer the brittle nanoporous material. We demonstrate this technique by using the same microfluidic system for membrane fabrication and subsequent liposome fusion onto the nanoporous support structure. The resulting bilayer formation is monitored by impedance spectroscopy across the nanoporous alumina membrane in real-time. Our approach offers a simple and efficient methodology to investigate the activity of transmembrane proteins or ion diffusion across membrane bilayers. PMID- 21977421 TI - Pore structure and surface area of silica SBA-15: influence of washing and scale up. AB - The removal of the surfactant (EO(20)PO(70)EO(20)) by washing before final calcination is a critical step in the synthesis of silica SBA-15. In contrast to washing with pure water or ethanol, washing with water and ethanol may, depending on the quantity of solvent used, alter the homogeneity and order of the pores, but also lead to an increase of the surface area of SBA-15. A reduction of solvent volume and a controlled washing protocol allow the synthesis of high surface area SBA-15 materials with a narrow monomodal pore size distribution. For larger batch sizes the influence of the quantity of solvent on the quality of the SBA-15 is reduced. PMID- 21977422 TI - Room temperature synthesis of indium tin oxide nanotubes with high precision wall thickness by electroless deposition. AB - Conductive nanotubes consisting of indium tin oxide (ITO) were fabricated by electroless deposition using ion track etched polycarbonate templates. To produce nanotubes (NTs) with thin walls and small surface roughness, the tubes were generated by a multi-step procedure under aqueous conditions. The approach reported below yields open end nanotubes with well defined outer diameter and wall thickness. In the past, zinc oxide films were mostly preferred and were synthesized using electroless deposition based on aqueous solutions. All these methods previously developed, are not adaptable in the case of ITO nanotubes, even with modifications. In the present work, therefore, we investigated the necessary conditions for the growth of ITO-NTs to achieve a wall thickness of around 10 nm. In addition, the effects of pH and reductive concentrations for the formation of ITO-NTs are also discussed. PMID- 21977423 TI - Schottky junction/ohmic contact behavior of a nanoporous TiO(2) thin film photoanode in contact with redox electrolyte solutions. AB - The nature and photoelectrochemical reactivity of nanoporous semiconductor electrodes have attracted a great deal of attention. Nanostructured materials have promising capabilities applicable for the construction of various photonic and electronic devices. In this paper, a mesoporous TiO(2) thin film photoanode was soaked in an aqueous methanol solution using an O(2)-reducing Pt-based cathode in contact with atmospheric air on the back side. It was shown from distinct photocurrents in the cyclic voltammogram (CV) that the nanosurface of the mesoporous n-TiO(2) film forms a Schottky junction with water containing a strong electron donor such as methanol. Formation of a Schottky junction (liquid junction) was also proved by Mott-Schottky plots at the mesoporous TiO(2) thin film photoanode, and the thickness of the space charge layer was estimated to be very thin, i.e., only 3.1 nm at -0.1 V vs Ag/AgCl. On the other hand, the presence of [Fe(CN)(6)](4-) and the absence of methanol brought about ohmic contact behavior on the TiO(2) film and exhibited reversible redox waves in the dark due to the [Fe(CN)(6)](4-/3-) couple. Further studies showed that multiple Schottky junctions/ohmic contact behavior inducing simultaneously both photocurrent and overlapped reversible redox waves was found in the CV of a nanoporous TiO(2) photoanode soaked in an aqueous redox electrolyte solution containing methanol and [Fe(CN)(6)](4-). That is, the TiO(2) nanosurface responds to [Fe(CN)(6)](4-) to give ohmic redox waves overlapped simultaneously with photocurrents due to the Schottky junction. Additionally, a second step photocurrent generation was observed in the presence of both MeOH and [Fe(CN)(6)](4-) around the redox potential of the iron complex. It was suggested that the iron complex forms a second Schottky junction for which the flat band potential (E(fb)) lies near the redox potential of the iron complex. PMID- 21977424 TI - Biomimetic materials. PMID- 21977425 TI - Superhydrophobic surfaces of the water bug Notonecta glauca: a model for friction reduction and air retention. AB - Superhydrophobic surfaces of plants and animals are of great interest for biomimetic applications. Whereas the self-cleaning properties of superhydrophobic surfaces have been extensively investigated, their ability to retain an air film while submerged under water has not, in the past, received much attention. Nevertheless, air retaining surfaces are of great economic and ecological interest because an air film can reduce friction of solid bodies sliding through the water. This opens perspectives for biomimetic applications such as low friction fluid transport or friction reduction on ship hulls. For such applications the durability of the air film is most important. While the air film on most superhydrophobic surfaces usually lasts no longer than a few days, a few semi-aquatic plants and insects are able to hold an air film over a longer time period. Currently, we found high air film persistence under hydrostatic conditions for the elytra of the backswimmer Notonecta glauca which we therefore have chosen for further investigations. In this study, we compare the micro- and nanostructure of selected body parts (sternites, upper side of elytra, underside of elytra) in reference to their air retaining properties. Our investigations demonstrate outstanding air film persistence of the upper side of the elytra of Notonecta glauca under hydrostatic and hydrodynamic conditions. This hierarchically structured surface was able to hold a complete air film under hydrostatic conditions for longer than 130 days while on other body parts with simple structures the air film showed gaps (underside of elytra) or even vanished completely after a few days (sternites). Moreover, the upper side of the elytra was able to keep an air film up to flow velocities of 5 m/s. Obviously the complex surface structure with tiny dense microtrichia and two types of larger specially shaped setae is relevant for this outstanding ability. Besides high air film persistence, the observation of a considerable fluid velocity directly at the air-water interface indicates the ability to reduce friction significantly. The combination of these two abilities makes these hierarchically structured surfaces extremely interesting as a biomimetic model for low friction fluid transport or drag reduction on ship hulls. PMID- 21977426 TI - Capillary origami: superhydrophobic ribbon surfaces and liquid marbles. AB - In the wetting of a solid by a liquid it is often assumed that the substrate is rigid. However, for an elastic substrate the rigidity depends on the cube of its thickness and so reduces rapidly as the substrate becomes thinner as it approaches becoming a thin sheet. In such circumstances, it has been shown that the capillary forces caused by a contacting droplet of a liquid can shape the solid rather than the solid shaping the liquid. A substrate can be bent and folded as a (pinned) droplet evaporates or even instantaneously and spontaneously wrapped on contact with a droplet. When this effect is used to create three dimensional shapes from initially flat sheets, the effect is called capillary origami or droplet wrapping.In this work, we consider how the conditions for the spontaneous, capillary induced, folding of a thin ribbon substrate might be altered by a rigid surface structure that, for a rigid substrate, would be expected to create Cassie-Baxter and Wenzel effects. For smooth thin substrates, droplet wrapping can occur for all liquids, including those for which the Young's law contact angle (defined by the interfacial tensions) is greater than 90 degrees and which would therefore normally be considered relatively hydrophobic. However, consideration of the balance between bending and interfacial energies suggests that the tendency for droplet wrapping can be suppressed for some liquids by providing the flexible solid surface with a rigid topographic structure. In general, it is known that when a liquid interacts with such a structure it can either fully penetrate the structure (the Wenzel case) or it can bridge between the asperities of the structure (the Cassie-Baxter case).In this report, we show theoretically that droplet wrapping should occur with both types of solid-liquid contact. We also derive a condition for the transition between the Cassie-Baxter and Wenzel type droplet wrapping and relate it to the same transition condition known to apply to superhydrophobic surfaces. The results are given for both droplets being wrapped by thin ribbons and for solid grains encapsulating droplets to form liquid marbles. PMID- 21977427 TI - Superhydrophobicity in perfection: the outstanding properties of the lotus leaf. AB - Lotus leaves have become an icon for superhydrophobicity and self-cleaning surfaces, and have led to the concept of the 'Lotus effect'. Although many other plants have superhydrophobic surfaces with almost similar contact angles, the lotus shows better stability and perfection of its water repellency. Here, we compare the relevant properties such as the micro- and nano-structure, the chemical composition of the waxes and the mechanical properties of lotus with its competitors. It soon becomes obvious that the upper epidermis of the lotus leaf has developed some unrivaled optimizations. The extraordinary shape and the density of the papillae are the basis for the extremely reduced contact area between surface and water drops. The exceptional dense layer of very small epicuticular wax tubules is a result of their unique chemical composition. The mechanical robustness of the papillae and the wax tubules reduce damage and are the basis for the perfection and durability of the water repellency. A reason for the optimization, particularly of the upper side of the lotus leaf, can be deduced from the fact that the stomata are located in the upper epidermis. Here, the impact of rain and contamination is higher than on the lower epidermis. The lotus plant has successfully developed an excellent protection for this delicate epistomatic surface of its leaves. PMID- 21977428 TI - Structural and magnetic properties of ternary Fe(1-)MnPt nanoalloys from first principles. AB - BACKGROUND: Structural and magnetic properties of binary Mn-Pt and ternary Fe(1-) (x)Mn(x)Pt nanoparticles in the size range of up to 2.5 nm (561 atoms) have been explored systematically by means of large scale first principles calculations in the framework of density functional theory. For each composition several magnetic and structural configurations have been compared. RESULTS: The concentration dependence of magnetization and structural properties of the ternary systems are in good agreement with previous bulk and thin film measurements. At an intermediate Mn-content around x = 0.25 a crossover between several phases with magnetic and structural properties is encountered, which may be interesting for exploitation in functional devices. CONCLUSION: Addition of Mn effectively increases the stability of single crystalline L1(0) particles over multiply twinned morphologies. This, however, compromises the stability of the ferromagnetic phase due to an increased number of antiferromagnetic interactions. The consequence is that only small additions of Mn can be tolerated for data recording applications. PMID- 21977429 TI - Functional morphology, biomechanics and biomimetic potential of stem-branch connections in Dracaena reflexa and Freycinetia insignis. AB - Branching in plants is one of the most important assets for developing large arborescent growth forms with complex crowns. While the form and development of branching in gymnosperms and dicotyledonous trees is widely understood, very little is known about branching patterns and the structure of branch-stem junctions in arborescent monocotyledons. For a better and quantitative understanding of the functional morphology of branch-stem-junctions in arborescent monocotyledons, we investigated the two species Dracaena reflexa and Freycinetia insignis. While D. reflexa is able to develop large arborescent forms with conspicuous crowns by anomalous secondary growth, F. insignis remains relatively small and is only capable of primary growth. Biomechanical investigations were performed by applying vertical loads up to rupture to lateral branches of both species. This allows the analysis of the fracture mechanics and the determination of the maximal force, stress and strain at rupture as well as the fracture toughness. Functional morphology was correlated with the mechanical behaviour of these plants and compared to data of other dicotyledonous trees. The high energy absorption found in the rupture process of lateral branches of D. reflexa and F. insignis makes them promising biological concept generators with a high potential for biomimetic implementation, i.e., for the development of branched fibre-reinforced technical composites. A wide range of constructional elements with branched (sub-)structures can be optimised by using solutions inspired by plant ramifications, e.g., in automotive and aerospace engineering, architecture, sports equipment and prosthetic manufacturing. PMID- 21977430 TI - Infrared receptors in pyrophilous ("fire loving") insects as model for new un cooled infrared sensors. AB - Beetles of the genus Melanophila and certain flat bugs of the genus Aradus actually approach forest fires. For the detection of fires and of hot surfaces the pyrophilous species of both genera have developed infrared (IR) receptors, which have developed from common hair mechanoreceptors. Thus, this type of insect IR receptor has been termed photomechanic and shows the following two special features: (i) The formation of a complex cuticular sphere consisting of an outer exocuticular shell as well as of a cavernous microfluidic core and (ii) the enclosure of the dendritic tip of the mechanosensitive neuron inside the core in a liquid-filled chamber. Most probably a photomechanic IR sensillum acts as a microfluidic converter of infrared radiation which leads to an increase in internal pressure inside the sphere, which is measured by a mechanosensitive neuron.A simple model for this biological IR sensor is a modified Golay sensor in which the gas has been replaced by a liquid. Here, the absorbed IR radiation results in a pressure increase of the liquid and the deflection of a thin membrane. For the evaluation of this model analytical formulas are presented, which permits the calculation of the pressure increase in the cavity, the deformation of the membrane and the time constant of an artificial leak to compensate ambient temperature changes. Some organic liquids with high thermal expansion coefficients may improve the deflection of the membrane compared to water. PMID- 21977431 TI - Zirconium nanoparticles prepared by the reduction of zirconium oxide using the RAPET method. AB - The aim of the current work is the synthesis and characterization of metallic Zr nanoparticles. The preparation is carried out by using the RAPET method (Reaction under Autogenic Pressure at Elevated Temperatures) developed in our lab. The RAPET reaction of commercial ZrO(2) with Mg powder was carried out in a closed stainless steel cell, at 750 degrees C. On completion of the reaction, the additionally formed MgO is removed by treatment with acid. The characterization of the product was performed by XRD, X-ray absorption spectroscopy, SEM, TEM and elemental analysis. The XRD pattern reveals that the product is composed of pure metallic zirconium, without any traces of the MgO by-product. PMID- 21977432 TI - Moisture harvesting and water transport through specialized micro-structures on the integument of lizards. AB - Several lizard species that live in arid areas have developed special abilities to collect water with their bodies' surfaces and to ingest the so collected moisture. This is called rain- or moisture-harvesting. The water can originate from air humidity, fog, dew, rain or even from humid soil. The integument (i.e., the skin plus skin derivatives such as scales) has developed features so that the water spreads and is soaked into a capillary system in between the reptiles' scales. Within this capillary system the water is transported to the mouth where it is ingested. We have investigated three different lizard species which have developed the ability for moisture harvesting independently, viz. the Australian thorny devil (Moloch horridus), the Arabian toadhead agama (Phrynocephalus arabicus) and the Texas horned lizard (Phrynosoma cornutum). All three lizards have a honeycomb like micro ornamentation on the outer surface of the scales and a complex capillary system in between the scales. By investigation of individual scales and by producing and characterising polymer replicas of the reptiles' integuments, we found that the honeycomb like structures render the surface superhydrophilic, most likely by holding a water film physically stable. Furthermore, the condensation of air humidity is improved on this surface by about 100% in comparison to unstructured surfaces. This allows the animals to collect moisture with their entire body surface. The collected water is transported into the capillary system. For Phrynosoma cornutum we found the interesting effect that, in contrast to the other two investigated species, the water flow in the capillary system is not uniform but directed to the mouth. Taken together we found that the micro ornamentation yields a superhydrophilic surface, and the semi-tubular capillaries allow for an efficient passive - and for Phrynosoma directed - transport of water. PMID- 21977433 TI - Sorting of droplets by migration on structured surfaces. AB - BACKGROUND: Controlled transport of microdroplets is a topic of interest for various applications. It is well known that liquid droplets move towards areas of minimum contact angle if placed on a flat solid surface exhibiting a gradient of contact angle. This effect can be utilised for droplet manipulation. In this contribution we describe how controlled droplet movement can be achieved by a surface pattern consisting of cones and funnels whose length scales are comparable to the droplet diameter. RESULTS: The surface energy of a droplet attached to a cone in a symmetry-preserving way can be smaller than the surface energy of a freely floating droplet. If the value of the contact angle is fixed and lies within a certain interval, then droplets sitting initially on a cone can gain energy by moving to adjacent cones. CONCLUSION: Surfaces covered with cone shaped protrusions or cavities may be devised for constructing "band-conveyors" for droplets. In our approach, it is essentially the surface structure which is varied, not the contact angle. It may be speculated that suitably patterned surfaces are also utilised in biological surfaces where a large variety of ornamentations and surface structuring are often observed. PMID- 21977434 TI - Detection of interaction between biomineralising proteins and calcium carbonate microcrystals. AB - The natural composite nacre is characterised by astonishing mechanical properties, although the main constituent is a brittle mineral shaped as tablets interdispersed by organic layers. To mimic the natural formation process which takes place at ambient conditions an understanding of the mechanism responsible for a defined microstructure of nacre is necessary. Since proteins are assumed to be involved in this mechanism, it is advantageous to identify distinct proteins interacting with minerals from the totality of proteins contained in nacre. Here, we adopted and modified a recently published approach given by Suzuki et al. [1] that gives a hint of specific protein-mineral interactions. Synthesised aragonite or calcite microcrystals were incubated with a protein mixture extracted from nacre of Haliotis laevigata. After incubation the mineral phase was dissolved and investigated for attached proteins. The results give a hint of one protein that seems to bind specifically to aragonite and not to calcite. The presented protocol seems to be suitable to detect mineral binding proteins quickly and therefore can point to proteins whose mineral binding capabilities should be investigated further. PMID- 21977435 TI - Hierarchically structured superhydrophobic flowers with low hysteresis of the wild pansy (Viola tricolor) - new design principles for biomimetic materials. AB - Hierarchically structured flower leaves (petals) of many plants are superhydrophobic, but water droplets do not roll-off when the surfaces are tilted. On such surfaces water droplets are in the "Cassie impregnating wetting state", which is also known as the "petal effect". By analyzing the petal surfaces of different species, we discovered interesting new wetting characteristics of the surface of the flower of the wild pansy (Viola tricolor). This surface is superhydrophobic with a static contact angle of 169 degrees and very low hysteresis, i.e., the petal effect does not exist and water droplets roll-off as from a lotus (Nelumbo nucifera) leaf. However, the surface of the wild pansy petal does not possess the wax crystals of the lotus leaf. Its petals exhibit high cone-shaped cells (average size 40 um) with a high aspect ratio (2.1) and a very fine cuticular folding (width 260 nm) on top. The applied water droplets are in the Cassie-Baxter wetting state and roll-off at inclination angles below 5 degrees . Fabricated hydrophobic polymer replicas of the wild pansy were prepared in an easy two-step moulding process and possess the same wetting characteristics as the original flowers. In this work we present a technical surface with a new superhydrophobic, low adhesive surface design, which combines the hierarchical structuring of petals with a wetting behavior similar to that of the lotus leaf. PMID- 21977436 TI - Extended X-ray absorption fine structure of bimetallic nanoparticles. AB - Electronic and magnetic properties strongly depend on the structure of the material, especially on the crystal symmetry and chemical environment. In nanoparticles, the break of symmetry at the surface may yield different physical properties with respect to the corresponding bulk material. A useful tool to investigate the electronic structure, magnetic behaviour and local crystallographic structure is X-ray absorption spectroscopy. In this review, recent developments in the field of extended X-ray absorption fine structure measurements and in the analysis methods for structural investigations of bimetallic nanoparticles are highlighted. The standard analysis based on Fourier transforms is compared to the relatively new field of wavelet transforms that have the potential to outperform traditional analysis, especially in bimetallic alloys. As an example, the lattice expansion and inhomogeneous alloying found in FePt nanoparticles is presented, and this is discussed below in terms of the influence of employed density functional theory calculations on the magnetic properties. PMID- 21977437 TI - The role of the cantilever in Kelvin probe force microscopy measurements. AB - The role of the cantilever in quantitative Kelvin probe force microscopy (KPFM) is rigorously analyzed. We use the boundary element method to calculate the point spread function of the measuring probe: Tip and cantilever. The calculations show that the cantilever has a very strong effect on the absolute value of the measured contact potential difference even under ultra-high vacuum conditions, and we demonstrate a good agreement between our model and KPFM measurements in ultra-high vacuum of NaCl monolayers grown on Cu(111). The effect of the oscillating cantilever shape on the KPFM resolution and sensitivity has been calculated and found to be relatively small. PMID- 21977438 TI - Recrystallization of tubules from natural lotus (Nelumbo nucifera) wax on a Au(111) surface. AB - We present here the first results on the self-assembly of tubules of natural wax from lotus leaves on a single crystal Au(111) surface. A comparison of the tubule growth on Au(111) to that on HOPG is discussed. Although the tubule formation on both Au(111) and HOPG takes place on an intermediate wax film which should mask the substrate properties, the tubule orientations differ. In contrast to a vertical tubule orientation on HOPG, the tubules lie flat on Au(111). Taking into account the physical properties of HOPG and Au(111), we put forward a hypothesis which can explain the different tubule orientations on both substrates. PMID- 21977439 TI - Effect of large mechanical stress on the magnetic properties of embedded Fe nanoparticles. AB - Magnetic nanoparticles are promising candidates for next generation high density magnetic data storage devices. Data storage requires precise control of the magnetic properties of materials, in which the magnetic anisotropy plays a dominant role. Since the total magneto-crystalline anisotropy energy scales with the particle volume, the storage density in media composed of individual nanoparticles is limited by the onset of superparamagnetism. One solution to overcome this limitation is the use of materials with extremely large magneto crystalline anisotropy. In this article, we follow an alternative approach by using magneto-elastic interactions to tailor the total effective magnetic anisotropy of the nanoparticles. By applying large biaxial stress to nanoparticles embedded in a non-magnetic film, it is demonstrated that a significant modification of the magnetic properties can be achieved. The stress is applied to the nanoparticles through expansion of the substrate during hydrogen loading. Experimental evidence for stress induced magnetic effects is presented based on temperature-dependent magnetization curves of superparamagnetic Fe particles. The results show the potential of the approach for adjusting the magnetic properties of nanoparticles, which is essential for application in future data storage media. PMID- 21977440 TI - Determination of object position, vortex shedding frequency and flow velocity using artificial lateral line canals. AB - The lateral line system of fish consists of superficial neuromasts, and neuromasts embedded in lateral line canals. Lateral line neuromasts allow fish to sense both minute water motions and pressure gradients, thereby enabling them to detect predators and prey or to recognize and discriminate stationary objects while passing them. With the aid of the lateral line, fish can also sense vortices caused by an upstream object or by undulatory swimming movements of fish. We show here that artificial lateral line canals equipped with optical flow sensors can be used to detect the water motions generated by a stationary vibrating sphere, the vortices caused by an upstream cylinder or the water (air) movements caused by a passing object. The hydrodynamic information retrieved from optical flow sensors can be used to calculate bulk flow velocity and thus the size of the cylinder that shed the vortices. Even a bilateral sensor platform equipped with only one artificial lateral line canal on each side is sufficient to determine the position of an upstream cylinder. PMID- 21977441 TI - Novel acridone-modified MCM-41 type silica: Synthesis, characterization and fluorescence tuning. AB - A Mobil Composition of Matter (MCM)-41 type mesoporous silica material containing N-propylacridone groups has been successfully prepared by co-condensation of an appropriate organic precursor with tetraethyl orthosilicate (TEOS) under alkaline sol-gel conditions. The resulting material was fully characterized by means of X ray diffraction (XRD), N(2)-adsorption-desorption, transmission electron microscopy (TEM), IR and UV-vis spectroscopy, as well as (29)Si and (13)C CP-MAS NMR techniques. The material features a high inner surface area and a highly ordered two-dimensional hexagonal pore structure. The fluorescence properties of the organic chromophore can be tuned via complexation of its carbonyl group with scandium triflate, which makes the material a good candidate for solid state sensors and optics. The successful synthesis of highly ordered MCM materials through co-condensation was found to be dependent on the chemical interaction of the different precursors. PMID- 21977442 TI - Studies towards synthesis, evolution and alignment characteristics of dense, millimeter long multiwalled carbon nanotube arrays. AB - We report the synthesis of aligned arrays of millimeter long carbon nanotubes (CNTs), from benzene and ferrocene as the molecular precursor and catalyst respectively, by a one-step chemical vapor deposition technique. The length of the grown CNTs depends on the reaction temperature and increases from ~85 um to ~1.4 mm when the synthesis temperature is raised from 650 to 1100 degrees C, while the tube diameter is almost independent of the preparation temperature and is ~80 nm. The parallel arrangement of the CNTs, as well as their tube diameter can be verified spectroscopically by small angle X-ray scattering (SAXS) studies. Based on electron diffraction scattering (EDS) studies of the top and the base of the CNT films, a root growth process can be deduced. PMID- 21977443 TI - The effect of surface anisotropy in the slippery zone of Nepenthes alata pitchers on beetle attachment. AB - The slippery zone in pitchers of the carnivorous plant Nepenthes alata bears scattered prominent lunate cells and displays continuous epicuticular crystalline wax coverage. The aim of this study was to examine the influence of the surface anisotropy, caused by the shape of lunate cells, on insect attachment ability. Traction tests with ladybird beetles Coccinella septempunctata were performed in two types of experiments, where surface samples of (1) intact pitchers, (2) chemically de-waxed pitchers, and (3) their polymer replicas were placed horizontally. Beetle traction forces were measured when they walked on test surfaces in either an upward (towards the peristome) or downward (towards the pitcher bottom) direction, corresponding to the upright or inverted positions of the pitcher. On intact pitcher surfaces covered with both lunate cells and wax crystals, experiments showed significantly higher forces in the direction towards the pitcher bottom. To distinguish between the contributions, from claw interlocking and pad adhesion, to insect attachment on the pitcher surfaces, intact versus claw-ablated beetles were used in the second type of experiment. On both de-waxed plant samples and their replicas, intact insects generated much higher forces in the downward direction compared to the upward one, whereas clawless insects did not. These results led to the conclusion that, (i) due to the particular shape of lunate cells, the pitcher surface has anisotropic properties in terms of insect attachment, and (ii) claws were mainly responsible for attachment enhancement in the downward pitcher direction, since, in this direction, they could interlock with overhanging edges of lunate cells. PMID- 21977444 TI - Dynamics of capillary infiltration of liquids into a highly aligned multi-walled carbon nanotube film. AB - The physical compatibility of a highly aligned carbon nanotube (HACNT) film with liquids was established using a fast and convenient experimental protocol. Two parameters were found to be decisive for the infiltration process. For a given density of nanotube packing, the thermodynamics of the infiltration process (wettability) were described by the contact angle between the nanotube wall and a liquid meniscus (theta). Once the wettability criterion (theta < 90 degrees ) was met, the HACNT film (of free volume equal to 91%) was penetrated gradually by the liquid in a rate that can be linearly correlated to dynamic viscosity of the liquid (eta). The experimental results follow the classical theory of capillarity for a steady process (Lucas-Washburn law), where the nanoscale capillary force, here supported by gravity, is compensated by viscous drag. This most general theory of capillarity can be applied in a prediction of both wettability of HACNT films and the dynamics of capillary rise in the intertube space in various technological applications. PMID- 21977445 TI - Formation of precise 2D Au particle arrays via thermally induced dewetting on pre patterned substrates. AB - The fabrication of precise 2D Au nanoparticle arrays over a large area is presented. The technique was based on pre-patterning of the substrate before the deposition of a thin Au film, and the creation of periodic particle arrays by subsequent dewetting induced by annealing. Two types of pre-patterned substrates were used: The first comprised an array of pyramidal pits and the second an array of circular holes. For the dewetting of Au films on the pyramidal pit substrate, the structural curvature-driven diffusion cooperates with capillarity-driven diffusion, resulting in the formation of precise 2D particle arrays for films within a structure dependent thickness-window. For the dewetting of Au films on the circular hole substrate, the periodic discontinuities in the films, induced by the deposition, can limit the diffusion paths and lead to the formation of one particle per individual separated region (holes or mesas between holes), and thus, result in the evolution of precise 2D particle arrays. The influence of the pre-patterned structures and the film thickness is analyzed and discussed. For both types of pre-patterned substrate, the Au film thickness had to be adjusted in a certain thickness-window in order to achieve the precise 2D particle arrays. PMID- 21977446 TI - Micro to nano: Surface size scale and superhydrophobicity. AB - This work looks at the fundamental question of how the surface mobility of drops in the composite state is related to the size scale of the roughness features of the surface. To this end, relevant literature is first reviewed and the important terms are clarified. We then describe and discuss contact and roll-off angle measurements on a set of hydrophobicized silicon post surfaces for which all parameters except for the surface size scale were held constant. It was found that a critical transition from "sticky superhydrophobic" (composite state with large contact angle hysteresis) to "truly superhydrophobic" (composite state with low hysteresis) takes place as the size of the surface features reaches 1 MUm. PMID- 21977447 TI - Dense lying self-organized GaAsSb quantum dots on GaAs for efficient lasers. AB - GaAsSb quantum dots (QDs) were grown on GaAs in the Stranski-Krastanov (SK) epitaxial mode. Their characteristics were dependent on the Sb/Ga (V/III) flux ratio and the growth temperature. The samples were grown with a V/III ratio between 0.45/1 and 1.50/1 and a temperature between 445 and 580 degrees C, not commonly used by other research groups. These parameters enabled the growth of dense lying dots with a density at least up to 6.5 * 10(10) cm(-2) and a diameter and height of 20 and 4 nm, respectively. The photoluminescence (PL) spectra revealed a QD peak at an emission wavelength between lambda = 0.876 and 1.035 MUm, depending on the exact conditions. Using a stack of such QD layers, an electrically pumped efficient QD laser was realized with an emission wavelength of lambda ~ 0.900 um at a temperature of 84 K. PMID- 21977448 TI - The epidemiology of diabetes in Korea. AB - Diabetes is an increasing global health problem worldwide. Diabetes and its complications have become a major cause of morbidity and mortality in Korea. The prevalence of diabetes in Korea has increased six- to seven-fold from 1.5% to 9.9% in the past 40 years. The prevalence of impaired fasting glucose also increased to about 20% in 2009. The International Diabetes Federation has estimated that the prevalence of diabetes will rise to 11.4% in 2030. Possible risk factors for diabetes in Korea are age, male gender, obesity, prediabetes, gestational diabetes, smoking, decreased physical activity, and short sleep duration. With increasing obesity, especially in childhood, and improved longevity, the prevalence of diabetes is expected to dramatically increase more than previously estimated. Therefore, public efforts to introduce healthy lifestyle changes and diabetic prevention programs are necessary to reduce the global epidemic of diabetes. PMID- 21977449 TI - Glycosphingolipid modification: structural diversity, functional and mechanistic integration of diabetes. AB - Glycosphingolipids (GSLs) are present in all mammalian cell plasma membranes and intracellular membrane structures. They are especially concentrated in plasma membrane lipid domains that are specialized for cell signaling. Plasma membranes have typical structures called rafts and caveola domain structures, with large amounts of sphingolipids, cholesterol, and sphingomyelin. GSLs are usually observed in many organs ubiquitously. However, GSLs, including over 400 derivatives, participate in diverse cellular functions. Several studies indicate that GSLs might have an effect on signal transduction related to insulin receptors and epidermal growth factor receptors. GSLs may modulate immune responses by transmitting signals from the exterior to the interior of the cell. Guillain-Barre syndrome is one of the autoimmune disorders characterized by symmetrical weakness in the muscles of the legs. The targets of the immune response are thought to be gangliosides, which are one group of GSLs. Other GSLs may serve as second messengers in several signaling pathways that are important to cell survival or programmed cell death. In the search for clear evidence that GSLs may play critical roles in various biological functions, many researchers have made genetically engineered mice. Before the era of gene manipulation, spontaneous animal models or chemical-induced disease models were used. PMID- 21977450 TI - Polymeric gene delivery for diabetic treatment. AB - Several polymers were used to delivery genes to diabetic animals. Polyaminobutyl glycolic acid was utilized to deliver IL-10 plasmid DNA to prevent autoimmune insulitis of non-obese diabetic (NOD) mouse. Polyethylene glycol grafted polylysine was combined with antisense glutamic acid decarboxylase (GAD) MRNA to represent GAD autoantigene expression. GLP1 and TSTA (SP-EX4) were delivered by bioreducible polymer to stop diabetic progression. Fas siRNA delivery was carried out to treat diabetic NOD mice animal. PMID- 21977452 TI - Prevalence, Awareness, and Control of Hypertension among Diabetic Koreans. PMID- 21977451 TI - Role of Peroxisome Proliferator-Activated Receptor alpha in Diabetic Nephropathy. AB - With a developing worldwide epidemic of diabetes mellitus, the renal complications associated with diabetes have become a serious health concern. Primary therapy for treating diabetic nephropathy is a multifactorial process. Peroxisome proliferator-activated receptor alpha (PPARalpha) agonists have been used primarily in clinical practice for the treatment of dyslipidemia and insulin resistance. Given that PPARalpha expression and regulation of metabolic pathways are involved in oxidative stress, inflammation, blood pressure regulation, and the renin-angiotensin aldosterone system, PPARalpha likely influences the development and pathogenesis of diabetic nephropathy via indirect effects on glucose and lipid homeostasis and also by direct action on the kidneys. These findings suggest that PPARalpha may become an important therapeutic target for treating diabetic renal complications. PMID- 21977453 TI - Effects of Sulfonylureas on Peroxisome Proliferator-Activated Receptor gamma Activity and on Glucose Uptake by Thiazolidinediones. AB - BACKGROUND: Sulfonylurea primarily stimulates insulin secretion by binding to its receptor on the pancreatic beta-cells. Recent studies have suggested that sulfonylureas induce insulin sensitivity through peroxisome proliferator activated receptor gamma (PPARgamma), one of the nuclear receptors. In this study, we investigated the effects of sulfonylurea on PPARgamma transcriptional activity and on the glucose uptake via PPARgamma. METHODS: Transcription reporter assays using Cos7 cells were performed to determine if specific sulfonylureas stimulate PPARgamma transactivation. Glimepiride, gliquidone, and glipizide (1 to 500 uM) were used as treatment, and rosiglitazone at 1 and 10 uM was used as a control. The effects of sulfonylurea and rosiglitazone treatments on the transcriptional activity of endogenous PPARgamma were observed. In addition, 3T3 L1 adipocytes were treated with rosiglitazone (10 uM), glimepiride (100 uM) or both to verify the effect of glimepiride on rosiglitazone-induced glucose uptake. RESULTS: Sulfonylureas, including glimepiride, gliquidone and glipizide, increased PPARgamma transcriptional activity, gliquidone being the most potent PPARgamma agonist. However, no additive effects were observed in the presence of rosiglitazone. When rosiglitazone was co-treated with glimepiride, PPARgamma transcriptional activity and glucose uptake were reduced compared to those after treatment with rosiglitazone alone. This competitive effect of glimepiride was observed only at high concentrations that are not achieved with clinical doses. CONCLUSION: Sulfonylureas like glimepiride, gliquidone and glipizide increased the transcriptional activity of PPARgamma. Also, glimepiride was able to reduce the effect of rosiglitazone on PPARgamma agonistic activity and glucose uptake. However, the competitive effect does not seem to occur at clinically feasible concentrations. PMID- 21977454 TI - Management of blood pressure in patients with type 2 diabetes mellitus: a nationwide survey in korean. AB - BACKGROUND: Hypertension is common in patients with type 2 diabetes, affecting up to 60% of patients. The Korean Diabetes Association performed a nationwide survey about prevalence, awareness and control of hypertension among diabetic Koreans. METHODS: The current survey included 3,859 diabetic patients recruited from 43 hospitals in Korea. Age, gender, height, weight and blood pressure (BP) were measured by standard methods. Data on fasting plasma glucose, glycosylated hemoglobin (HbA1c), awareness of hypertension, and compliance of antihypertensive medication were collected via interview and reviewed using patient medical records. RESULTS: A total of 57.5% of all patients were >60 years old. Their mean HbA1c was 7.6+/-1.5%. Among antihypertensive medication users, 39.9% had <130 mm Hg and <80 mm Hg, whereas 60.1% had >=130 mm Hg or >=80 mm Hg. The answer "BP is under good control" was given by 75.1% of the antihypertensive medication users. Out of these patients, 26.4% had <130 mm Hg and <80 mm Hg, whereas 73.6% had >=130 mm Hg or >=80 mm Hg. A total of 75.5% of antihypertensive medication users answered that they had taken their antihypertensive medication every day for the past 2 weeks. "Forgetfulness" was most frequently the reason of non-compliance for patients that did not take their antihypertensive medication regularly. CONCLUSION: Approximately one third of the patients with diabetes were found to reach target blood pressure control in the 43 hospitals across Korea. Stricter control is needed to reduce severe complications of diabetes in Korea. PMID- 21977455 TI - A Comparative Study of Eating Habits and Food Intake in Women with Gestational Diabetes according to Early Postpartum Glucose Tolerance Status. AB - BACKGROUND: Women with gestational diabetes mellitus (GDM) are at high risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD); continuous life style intervention, especially diet, is central to managing T2DM and CVD. However, little is known about the dietary patterns of women with GDM after delivery. The goal of this study was to compare the eating habits and food intakes of women diagnosed with GDM during the early postpartum period. METHODS: We performed a 75 g oral glucose tolerance test (OGTT) in 184 women with GDM between 6 and 12 weeks after delivery. Based on the results of the OGTT, the subjects were divided into three groups according to the American Diabetes Association criteria; normal glucose tolerance (NGT) (n=100), pre-diabetes (n=73), and diabetes mellitus (DM) (n=11). Eating habits and usual food intake after delivery were investigated using a questionnaire, based on 24 hour-recall, which was administered by a trained dietitian. The daily intake data were analyzed using CAN Pro 3.0. Blood tests were performed pre- and post-delivery. RESULTS: Eating habits were not significantly different among the three groups. However, animal fat consumption was significantly different among the three groups. The intake ratio of fat calories to total calories was also significantly higher in the pre-diabetes and DM groups. CONCLUSION: Although diet in the period 6 to 12 weeks postpartum did not influence glucose level, it may be important to educate women with GDM about the risks of excessive animal fat intake during pregnancy and the postpartum period in order to prevent later onset of T2DM. PMID- 21977456 TI - Effects of Aerobic Exercise vs. Resistance Training on Endothelial Function in Women with Type 2 Diabetes Mellitus. AB - BACKGROUND: There is controversy over whether aerobic or resistance exercise is more effective for improving endothelial function in type 2 diabetes mellitus (T2DM). This study was aimed to investigate the effects of an aerobic and resistance training program on endothelial function, and the influences of glycemic control, body weight changes, and aerobic capacity in T2DM. METHODS: Total 40 overweight women with T2DM were assigned into 3 groups: an aerobic exercise group (AEG, n=13), resistance exercise group (REG, n=12), and control group (CG, n=15), and followed either brisk walking for the AEG or resistance band training for the REG, 60 minutes per day, 5 days per week for 12 weeks with monitoring daily activity using accelerometers. We assessed endothelial function by flow-mediated dilation (FMD), and aerobic capacity by oxygen uptake at anaerobic threshold (AT_VO(2)) at baseline and following training program. RESULTS: The mean participants' age was 57.0+/-6.8 years, and body mass index (BMI) was 27.0+/-2.3 kg/m(2). After intervention, FMD increased by 2.2+/-1.9% in AEG, which differed from REG and CG (P=0.002), despite of decreased body weight (BW) in both AG and RG (2.8+/-2.5%, P=0.002; 1.6+/-2.0%, P=0.017, respectively). A significant increased AT_VO(2) and decreased HbA1c were found only in AEG. In all participants, FMD was changed with the significant relations to the AT_VO(2) (r=0.348, P=0.035), but not to HbA1c levels or BW. CONCLUSION: Aerobic exercise appears to be more beneficial than resistance exercise for improving endothelial function in T2DM. In addition, aerobic capacity could be a better predictor of changes in FMD than BW and glycemic control. PMID- 21977457 TI - The Correlations between Extremity Circumferences with Total and Regional Amounts of Skeletal Muscle and Muscle Strength in Obese Women with Type 2 Diabetes. AB - BACKGROUND: Insulin resistance is related to central obesity and the amount of skeletal muscle. A simple and practical anthropometric marker for muscle mass is not known, although waist circumference (WC) is used as an indicator of abdominal obesity. The aims of this study were to investigate whether arm (AC) and thigh circumferences (TC) can be used as an indicator of muscle mass and if they are related to muscle strength. METHODS: A total of 110 obese (body mass index [BMI]>=25 kg/m(2)) women with type 2 diabetes were enrolled, and WC, AC, and TC were measured. Abdominal visceral fat (AVF), subcutaneous fat (ASF), and total fat (ATF) were assessed by computed tomography, regional muscle (MM), and fat mass by dual-energy X-ray absorptiometry, muscle strength by one repetition maximum (1RM) of both extremities (chest and leg press) and insulin resistance by K(ITT). RESULTS: The mean age was 56.2+/-7.3 years, duration of diabetes was 4.2+/-4.4 years, and BMI was 27.2+/-2.8 kg/m(2). WC was correlated with ATF, AVF, and ASF (r=0.728, P<0.001; r=0.515, P<0.001; r=0.608, P<0.001, respectively). Arm MM was correlated with AC (r=0.500, P<0.001), and leg MM with TC (r=0.291, P=0.002). Upper 1RM was related to AC/WC ratio (r=0.359, P<0.001), and lower 1RM was to TC/WC ratio (r=0.286, P=0.003). Insulin resistance had significant relations with AVF, WC, and total MM (r=-0.262, P=0.008; r=-0.217, P=0.029; r=0.160, P=0.031, respectively). CONCLUSION: The muscle mass was related to extremity circumferences, and muscle strength was to extremity/waist circumference ratio in obese women with type 2 diabetes. PMID- 21977458 TI - Long menstrual cycle is associated with type 2 diabetes mellitus in korean women. AB - BACKGROUND: Long menstrual cycle is a risk factor for developing type 2 diabetes and cardiovascular disease in women. We aimed to evaluate the association between existing type 2 diabetes and oligomenorrhea before diagnosis of diabetes, and to observe the differences in this association among obese and non-obese Korean women. METHODS: Patients with type 2 diabetes (n=118) and without any clinical evidence of abnormal glucose regulation (n=258) who attended the outpatient clinic of a university hospital and were over age 30. Patients self-reporting a menstrual cycle over 40 days during their 20s were defined as oligomenorrhea before diagnosis of diabetes. Obesity was defined as having a body mass index (BMI) over 25 kg/m(2). RESULTS: The frequency of oligomenorrhea before diagnosis of diabetes was almost two-fold higher in women with type 2 diabetes than in the control group (16.1% vs. 8.5%, P=0.03). Oligomenorrhea was associated with type 2 diabetes after adjusting for age, BMI, systolic blood pressure, triglycerides, and high density lipoprotein cholesterol (odds ratio, 3.89; 95% confidence interval, 1.37 to 11.04). Among women with oligomenorrhea before diagnosis of diabetes, the frequency of type 2 diabetes was significantly higher in obese subjects than in their non-obese counterparts (90.9% vs. 30.0%, P=0.03). CONCLUSION: Having a long menstrual cycle could be a risk factor for the development of type 2 diabetes, especially in obese women. PMID- 21977459 TI - Association between Diabetic Polyneuropathy and Cardiovascular Complications in Type 2 Diabetic Patients. AB - BACKGROUND: Diabetes mellitus is a major independent risk factor for cardiovascular disease (CVD), but high cardiovascular risk in diabetes mellitus patients is not completely explained by clustering traditional risk factors. Recently, associations between diabetic polyneuropathy (DPN) and macrovasculopathy have been suggested. We aimed to assess associations between DPN and cardiovascular complications in type 2 diabetic patients. METHODS: Microvascular and cardiovascular complications were evaluated in 1,041 type 2 diabetic patients. RESULTS: In patients with DPN, the age, prevalence of hypertension, diabetes duration, systolic blood pressure, pulse pressure, and hemoglobin glycation (HbA1c) levels were significantly higher, while the high density lipoprotein cholesterol (HDL-C) levels were lower than in those without DPN. The prevalence of CVD was higher in patients with DPN. In multivariate analysis, DPN was independently associated with CVD (odds ratio, 1.801; 95% confidence interval, 1.009 to 3.214). CONCLUSION: Our results showed that DPN was associated with a high prevalence of cardiovascular disease in type 2 diabetic patients, but further studies are needed to investigate the causative nature of associations between DPN and CVD. PMID- 21977460 TI - Comparison of Attitudes Regarding Quality of Life between Insulin-Treated Subjects with Diabetes Mellitus and Healthy Populations. AB - BACKGROUND: Diabetes mellitus is a chronic disease and one of the main causes of mortality in developing countries. The main objective of treating all chronic diseases, of course, is to improve well-being and attain a satisfactory quality of life (QOL). The major goal of this study is comparison of attitude toward QOL in insulin-dependent subjects with diabetes mellitus and healthy subjects. METHODS: In this study, insulin-dependent subjects with diabetes mellitus and healthy subjects were gathered via convenience sampling. The subjects were asked to complete the Hanestad & Albrektsen Attitude to Quality of Life Questionnaire. The questionnaire evaluates five quality of life dimensions-physical, social, mental-emotional, behavioral-activity, and economic-using a scoring system similar to the Likert scale. The Wilcoxon test was used to compare scores between the two groups. RESULTS: The mean total score on attitude toward QOL in the healthy control group was 53.8, and it in the insulin-dependent subjects with diabetes mellitus group was 35.9. The mean total score of attitude toward QOL in the physical dimension, mental-emotional and feelings of well-being dimension, and behavioral-activity dimension were significantly higher in the healthy population than they were in diabetes mellitus groups. Such a difference was not seen in the social and economic dimensions. CONCLUSION: Since the attitudes of insulin-dependent subjects with diabetes mellitus toward QOL are used as an index of individual and societal health levels, it appears that this group may benefit from education and professional counseling to improve their QOLs. PMID- 21977461 TI - Postprandial Triglyceride Is Associated with Fasting Triglyceride and HOMA-IR in Korean Subjects with Type 2 Diabetes. AB - BACKGROUND: Recent studies indicate postprandial triglyceride (TG) had a better association with cardiovascular events and metabolic syndrome than fasting TG. The authors of the present study investigated the metabolic and clinical relevance of postprandial TG. METHODS: In a cross-sectional retrospective study, the authors of the present study compared fasting and postprandial TG and analyzed the relationship between postprandial TG and various demographic and metabolic parameters in 639 Korean subjects with type 2 diabetes (T2D, group I, n=539) and impaired fasting glucose (IFG, group II, n=100) after ingestion of a standardized liquid meal (total 500 kcal, 17.5 g fat, 68.5 g carbohydrate, and 17.5 g protein). RESULTS: Fasting and postprandial TG were significantly correlated (r=0.973, r=0.937, P<0.001) in group I and II, respectively. Of the variables, total cholesterol, waist circumference and body mass index were significantly correlated with fasting and postprandial TG in both groups. Only postprandial TG showed a significant correlation with glucose metabolic parameters (e.g., postprandial glucose, homeostatic model assessment of insulin resistance [HOMA-IR], and fasting C-peptide) in subjects with T2D. Multiple regression analysis showed fasting TG and HOMA-IR could be predictable variables for postprandial TG in subjects with T2D. CONCLUSION: Postprandial TG was very strongly correlated with fasting TG. The authors of the present study suggest insulin resistance may be more associated with postprandial TG than fasting TG in Korean T2D patients on a low-fat diet. PMID- 21977462 TI - Efficacy of sitagliptin when added to ongoing therapy in korean subjects with type 2 diabetes mellitus. AB - BACKGROUND: To evaluate the clinical efficacy of sitagliptin for reducing plasma glucose levels in Korean subjects with type 2 diabetes mellitus during a 14-week treatment period. METHODS: Our study design involved the addition of 100 mg sitagliptin once-daily to three ongoing combination therapy regimens and changing from glimepiride and metformin to sitagliptin and metformin. RESULTS: The addition of sitagliptin 100 mg/day produced a statistically significant reduction in mean HbA1c level (mean HbA1c reduction of 0.99+/-0.85%, P<0.01). In the group taking a combination of sitagliptin and metformin (n=143, initial mean HbA1c level=7.48%), the reductions in HbA1c, 2-hour postprandial glucose, and fasting glucose levels were 0.72+/-0.76% (P<0.01), 47+/-65 mg/dL (P<0.01), and 15+/-44 mg/dL (P<0.01), respectively. In the group taking a combination of sitagliptin, glimepiride, and metformin (n=125, initial mean HbA1c level=8.42%), the reductions in HbA1c, 2-hour postprandial glucose, and fasting glucose levels were 1.09+/-0.86% (P<0.01), 62+/-64 mg/dL (P<0.01), and 31+/-45 mg/dL (P<0.01), respectively. In the group taking a combination of sitagliptin, glimepiride, metformin, and alpha-glucosidase inhibitor (n=63, initial mean HbA1c level=9.19%), the reductions in HbA1c, 2-hour postprandial glucose, and fasting glucose levels were 1.27+/-0.70% (P<0.01), 72+/-65 mg/dL (P<0.01), and 35+/-51 mg/dL (P<0.01), respectively. In the group that had previous hypoglycemic events and that changed from glimepiride to sitagliptin, HbA1c level did not change but fasting glucose increased significantly (14+/-29 mg/dL, P<0.01). CONCLUSION: Sitagliptin combination therapy for 14 weeks significantly improved glycemic control and was well-tolerated in Korean subjects with type 2 diabetes mellitus. PMID- 21977464 TI - Letter: the effect of an Angiotensin receptor blocker on arterial stiffness in type 2 diabetes mellitus patients with hypertension (diabetes metab j 2011;35:236 42). PMID- 21977463 TI - Effects of resistance training and aerobic exercise on insulin sensitivity in overweight korean adolescents: a controlled randomized trial. AB - BACKGROUND: Data on the impact of resistance training on insulin resistance in overweight or obese children are inconclusive. METHODS: Thirty overweight South Korean adolescents (mean age of 13.10 years) were divided by sex, and then randomly assigned to one of three treatment groups, which were the diet only (DO), diet with aerobic exercise (AE), or diet with resistance training (RT) group. Physiologic and metabolic parameters were assessed at baseline and after 12 weeks of exercise training and diet modification. RESULTS: Both exercise groups (aerobic and resistance) showed significant improvements in their insulin area under the curve and insulin sensitivity index values when compared to their baseline values while the DO group showed no significant changes in these variables. Age-, sex-, and body mass index (BMI)-adjusted intergroup comparison analyses showed a marked reduction in BMI and a significant reduction in muscle mass in the AE group when compared to the RT group and the DO group, respectively. CONCLUSION: A 12-week exercise training program of either resistance or aerobic activity improved insulin sensitivity in overweight adolescents, although it failed to show superiority over a DO program. Aerobic exercise decreased both body weight and BMI, and it was noted that this group also had a significant reduction in muscle mass when compared to the DO group. PMID- 21977465 TI - Response: the effect of an Angiotensin receptor blocker on arterial stiffness in type 2 diabetes mellitus patients with hypertension (diabetes metab j 2011;35:236 42). PMID- 21977466 TI - Assessment of panoramic radiography as a national oral examination tool: review of the literature. AB - PURPOSE: The purpose of this review is to evaluate the possibility of panoramic radiography as a national oral examination tool. MATERIALS AND METHODS: This report was carried out by review of the literatures. RESULTS: Panoramic radiography has sufficient diagnostic accuracy in dental caries, periodontal diseases, and other lesions. Also, the effective dose of panoramic radiography is lower than traditional full-mouth periapical radiography. CONCLUSION: Panoramic radiography will improve the efficacy of dental examination in national oral examination. However, more studies are required to evaluate the benefit, financial cost, and operation time and also to make selection criteria and quality management program. PMID- 21977467 TI - Direct digital radiography versus conventional radiography for estimation of canal length in curved canals. AB - PURPOSE: The purpose of this study was to compare the conventional and digital radiography in the estimation of working length in mandibular molars. MATERIALS AND METHODS: Sixty molar teeth were selected and divided into three groups in the basis of canal curves (0-15 degrees , 15-30 degrees , >30 degrees ). After the placement of a 15 K-file, radiographs were taken with a conventional film (F speed) and a digital sensor. Canal lengths were measured in these images by two observers. Statistical analysis was performed with repeated measures of ANOVA and paired sample t-test with 95% confidence. RESULTS: There was a high inter observer agreement on the measurements of working length in conventional and digital radiographs. There was no significant difference between the mean values of measurements in conventional and digital radiography. Moreover, there was no significant difference between conventional and digital radiography with the actual values in the basis of canal curves. CONCLUSION: The accuracy of conventional and digital radiography in the determination of the working length was in an acceptable range. PMID- 21977468 TI - Effect of LCD monitor type and observer experience on diagnostic performance in soft-copy interpretations of the maxillary sinus on panoramic radiographs. AB - PURPOSE: The aim of this study was to evaluate the effect of liquid crystal display (LCD) monitor type and observer experience on the diagnostic performance in soft-copy interpretations of maxillary sinus inflammatory lesions on panoramic radiographs. MATERIALS AND METHODS: Ninety maxillary sinuses on panoramic images were grouped into negative and positive groups according to the presence of inflammatory lesions, using CT for confirmation. Monochrome and color LCDs were used. Six observers participated and ROC analysis was performed to evaluate the diagnostic performance. The reading time, fatigue score, and inter-/intra observer agreements were assessed. RESULTS: The interpretation of maxillary sinus inflammatory lesions was affected by the LCD monitor type used and by the experience of the observer. The reading time was not significantly different, however the fatigue score was significantly different between two LCD monitors. Inter-observer agreement was relatively good in experienced observers, while the intra-observer agreement for all observers was good with monochrome LCD but not with color LCD. CONCLUSION: The less experienced observers showed lowered diagnostic ability with a general color LCD. PMID- 21977469 TI - External root resorption after orthodontic treatment: a study of contributing factors. AB - PURPOSE: The purpose of this study was to examine the patient- and treatment related etiologic factors of external root resorption. MATERIALS AND METHODS: This study consisted of 163 patients who had completed orthodontic treatments and taken the pre- and post-treatment panoramic and lateral cephalometric radiographs. The length of tooth was measured from the tooth apex to the incisal edge or cusp tip on the panoramic radiograph. Overbite and overjet were measured from the pre- and post-treatment lateral cephalometric radiographs. The root resorption of each tooth and the factors of malocclusion were analyzed with an analysis of variance. A paired t test was performed to compare the mean amount of root resorption between male and female, between extraction and non-extraction cases, and between surgery and non-surgery groups. Correlation coefficients were measured to assess the relationship between the amount of root resorption and the age in which the orthodontic treatment started, the degree of changes in overbite and overjet, and the duration of treatment. RESULTS: Maxillary central incisor was the most resorbed tooth, followed by the maxillary lateral incisor, the mandibular central incisor, and the mandibular lateral incisor. The history of tooth extraction was significantly associated with the root resorption. The duration of orthodontic treatment was positively correlated with the amount of root resorption. CONCLUSION: These findings show that orthodontic treatment should be carefully performed in patients who need the treatment for a long period and with a pre-treatment extraction of teeth. PMID- 21977470 TI - Computed tomographic features of fibrous dysplasia of maxillofacial region. AB - PURPOSE: This study was to find the computed tomographic features of fibrous dysplasia of the maxillofacial region. MATERIALS AND METHODS: All eight cases included in the study reported either to Government Dental College and Hospital or Nair Hospital Dental College, Mumbai between 2003 and 2009. The patients were prescribed computed tomogram in addition to conventional radiographs of maxillofacial region which were studied for characteristic features of fibrous dysplasia. The diagnosis of fibrous dysplasia was confirmed by histopathological report. RESULTS: All cases showed the ill-defined margins of lesions except in the region where the lesions were extending to cortex of the involved bone. Internal structure of all cases showed ground glass appearance. Four cases of maxillary lesion showed the displacement of maxillary sinus maintaining the shape of maxillary sinus. Two cases showed complete obliteration of maxillary sinus. Displacement of inferior alveolar canal did not follow any typical pattern in any of the cases but was displaced in different directions. CONCLUSION: The craniofacial type of fibrous dysplasia is as common as fibrous dysplasia of jaw. The margins, extent, internal structure and effect on surrounding structure are well detected on computed tomographic images. PMID- 21977471 TI - Unicystic ameloblastoma with diverse mural proliferation - a hybrid lesion. AB - A 46-year-old man was referred to our hospital for treatment, complaining of swelling on the right mandibular molar region. Radiographic examination revealed a well defined multilocular radiolucent lesion with root resorption of right lower anteriors and molars. Following biopsy, a diagnosis of unicystic ameloblastoma of mural type was made and hemimandibulectomy was performed under general anesthesia. Histopathological examination of the surgical specimen exhibited a unicystic ameloblastoma of luminal, intraluminal, and mural type. Intraluminal proliferation was of plexiform pattern and mural proliferation showed unusual histopathological findings, which revealed follicular, acanthomatous areas coexisted with desmoplastic areas. This mural picture was similar to the so-called 'hybrid lesion of ameloblastoma', whose biological profile is not elicited due to the lack of adequate published reports. Two years follow up till date has not revealed any signs of recurrence. PMID- 21977472 TI - Necrotizing sialometaplasia of palate: a case report. AB - Necrotizing sialometaplasia (NS) which mimics malignancy both clinically and histopathologically is an uncommon benign, self-limiting inflammatory disease of the mucus-secreting minor salivary glands. The lesion is believed to be the result of vascular ischemia that may be initiated by trauma. Till date, the diagnosis of NS remains a challenge. This report demonstrates a case of NS in a 73-year-old male patient who presented with an ulcerative lesion in his palate. He had a history of local trauma and was long-term user of salbutamol inhaler. An incisional biopsy was carried out and the diagnosis was established through history, clinical examination, histopathology using Hematoxylin and Eosin stain. The patient was given symptomatic treatment and the lesion healed in about 7 weeks. PMID- 21977473 TI - Unilateral segmental odontomaxillary hypoplasia: an unusual case report. AB - Facial asymmetry is not an uncommon occurrence in day to day dental practice. It can be caused by various etiologic factors ranging from facial trauma to serious hereditary conditions. Here, we report a rare case of non-syndromic facial asymmetry in a young female, who was born with this condition but was not aware of the progression of asymmetry. No relevant family history was recognized. She was also deficient in both deciduous and permanent teeth in the corresponding region of maxilla. Hence, the cause of this asymmetry was believed to be a segmental odontomaxillary hypoplasia of left maxilla accompanied by agenesis of left maxillary premolars and molars and disuse atrophy of corresponding facial musculature. This report briefly discussed the comparative features of segmental odontomaxillary hypoplasia, hemimaxillofacial dysplasia, and segmental odontomaxillary dysplasia and justified the differences between segmental odontomaxillary hypoplasia and the other two conditions. PMID- 21977474 TI - Current status of dental caries diagnosis using cone beam computed tomography. AB - PURPOSE: The purpose of this article is to review the current status of dental caries diagnosis using cone beam computed tomography (CBCT). MATERIALS AND METHODS: An online PubMed search was performed to identify studies on caries research using CBCT. RESULTS: Despite its usefulness, there were inherent limitations in the detection of caries lesions through conventional radiograph mainly due to the two-dimensional (2D) representation of caries lesions. Several efforts were made to investigate the three-dimensional (3D) image of lesion, only to gain little popularity. Recently, CBCT was introduced and has been used for diagnosis of caries in several reports. Some of them maintained the superiority of CBCT systems, however it is still under controversies. CONCLUSION: The CBCT systems are promising, however they should not be considered as a primary choice of caries diagnosis in everyday practice yet. Further studies under more standardized condition should be performed in the near future. PMID- 21977475 TI - Diagnostic performance of dental students in identifying mandibular condyle fractures by panoramic radiography and the usefulness of reference images. AB - PURPOSE: The purpose of this study was to evaluate the diagnostic performance of dental students in detection of mandibular condyle fractures and the effectiveness of reference panoramic images. MATERIALS AND METHODS: Forty-six undergraduates evaluated 25 panoramic radiographs for condylar fractures and the data were analyzed through receiver operating characteristic (ROC) analysis. After a month, they were divided into two homogeneous groups based on the first results and re-evaluated the images with (group A) or without (group B) reference images. Eight reference images included indications showing either typical condylar fractures or anatomic structures which could be confused with fractures. Paired t-test was used for statistical analysis of the difference between the first and the second evaluations for each group, and student's t-test was used between the two groups in the second evaluation. The intra- and inter-observer agreements were evaluated with Kappa statistics. RESULTS: Intra- and inter observer agreements were substantial (k=0.66) and moderate (k=0.53), respectively. The area under the ROC curve (Az) in the first evaluation was 0.802. In the second evaluation, it was increased to 0.823 for group A and 0.814 for group B. The difference between the first and second evaluations for group A was statistically significant (p<0.05), however there was no statistically significant difference between the two groups in the second evaluation. CONCLUSION: Providing reference images to less experienced clinicians would be a good way to improve the diagnostic ability in detecting condylar fracture. PMID- 21977476 TI - Assessment of the increased calcification of the jaw bone with CT-Scan after dental implant placement. AB - PURPOSE: This study was performed to evaluate the changes of jaw bone density around the dental implant after placement using computed tomography scan (CT Scan). MATERIALS AND METHODS: This retrospective study consisted of 30 patients who had lost 1 posterior tooth in maxilla or mandible and installed dental implant. The patients took CT-Scan before and after implant placement. Hounsfield Unit (HU) was measured around the implants and evaluated the difference of HU before and after implant installation. RESULTS: The mean HU of jaw bone was 542.436 HU and 764.9 HU before and after implant placement, respectively (p<0.05). The means HUs for male were 632.3 HU and 932.2 HU and those for female 478.2 HU and 645.5 HU before and after implant placement, respectively (p<0.05). Also, the jaw bone with lower density needed longer period for implant procedure and the increased change of HU of jaw bone was less in the cases which needed longer period for osseointegration. CONCLUSION: CT-Scan could be used to assess the change of bone density around dental implants. Bone density around dental implant was increased after placement. The increased rate of bone density could be determined by the quality of jaw bone before implant placement. PMID- 21977477 TI - Quantitative localization of impacted mesiodens using panoramic and periapical radiographs. AB - PURPOSE: The purpose of this study was to evaluate a new technique for localizing impacted mesiodens using its horizontal magnification ratio on panoramic radiographs. MATERIALS AND METHODS: Location-magnification equation of a panoramic equipment was obtained from horizontal magnification ratio of a metal ball which was located variable positions from the center of image layer at interval of 2 mm. Panoramic radiographs were obtained from a skull phantom with a metal ball which was a substitute for impacted mesiodens and was embedded 10mm(Group 1), 15mm(Group 2), and 20mm(Group 3) posterior to the central incisor. Each group obtained 7 panoramic radiographs at variable positions and one periapical radiograph. Three methods were used to estimate the actual width of the incisors and the balls which were used to calculate the magnification ratio. The methods included using the actual incisor width and the calculated ball width (Method 1), using the actual incisor width and the ball widths measured on periapical radiograph (Method 2), and using the incisor and the ball widths measured on periapical radiograph (Method 3). The location of the metal ball was calculated by using the location-magnification equation. RESULTS: The smallest difference between the calculated and the actual distance was 0.1+/-0.7 mm in Group 1/Method 3. The largest difference was -4.2+/-1.6 mm in Group 3/Method 2. In all groups, method 3 was the most accurate. CONCLUSION: Quantitative localization of impacted mesiodens is possible by using panoramic radiograph. PMID- 21977478 TI - Fractal analysis of mandibular trabecular bone: optimal tile sizes for the tile counting method. AB - PURPOSE: This study was performed to determine the optimal tile size for the fractal dimension of the mandibular trabecular bone using a tile counting method. MATERIALS AND METHODS: Digital intraoral radiographic images were obtained at the mandibular angle, molar, premolar, and incisor regions of 29 human dry mandibles. After preprocessing, the parameters representing morphometric characteristics of the trabecular bone were calculated. The fractal dimensions of the processed images were analyzed in various tile sizes by the tile counting method. RESULTS: The optimal range of tile size was 0.132 mm to 0.396 mm for the fractal dimension using the tile counting method. The sizes were closely related to the morphometric parameters. CONCLUSION: The fractal dimension of mandibular trabecular bone, as calculated with the tile counting method, can be best characterized with a range of tile sizes from 0.132 to 0.396 mm. PMID- 21977480 TI - Central odontogenic fibroma: a case report. AB - Central odontogenic fibroma is a rare odontogenic neoplasm that originates from odontogenic ectomesenchyme. Here, a case of central odontogenic fibroma in a 17 year-old male is reported. Since the present case showed a multilocular radiolucency with partially ill-defined border between the right mandibular condyle and the distal root of the right mandibular third molar, differential diagnosis involved a wide range of pathosis from benign lesions like ameoloblastic fibroma and odontogenic myxoma to more aggressive lesions such as desmoplastic fibroma, juvenile aggressive fibromatosis, or fibrosarcoma. PMID- 21977479 TI - Determination of midsagittal plane for evaluation of facial asymmetry using three dimensional computed tomography. AB - PURPOSE: The aim of the present study was to investigate the disagreement of cephalometric analysis depending on the reference determination of midsagittal plane on three-dimensional computed tomography. MATERIALS AND METHODS: A total of 102 young women with class III dentofacial deformity were evaluated using three dimensional computed tomography. The cranial and facial midsagittal planes were defined and the amounts of jaw deviation were calculated. The amounts of jaw deviation were compared with paired t-test (2-tailed) and Bland-Altman plot was drawn. RESULTS: The landmark tracing were reproducible (r>=.978). The jaws relative to the cranial midsagittal plane were 10-17 times more significantly deviated than to the facial midsagittal plane (P<.001). Bland-Altman plot demonstrated that the differences between the amounts of jaw deviation from two midsagittal planes were not normally distributed versus the average of the amounts of jaw deviation from two midsagittal planes. CONCLUSION: The cephalometric analyses of facial asymmetry were significantly inconsistent depending on the reference determination of midsagittal plane. The reference for midsagittal plane should be carefully determined in three-dimensional cephalometric analysis of facial asymmetry of patients with class III dentofacial deformity. PMID- 21977481 TI - Intraosseous ameloblastoma masquerading as exophytic growth: a case report. AB - Intraosseous ameloblastoma is the most common and simple type of ameloblastoma prevalent among odontogenic tumors. Clinico-radiographically intraosseous ameloblastoma presents as slow, painless swelling or expansion of the jaws and described as multilocular expansile radiolucency that occurs most frequently in mandibular molar/ramus area. This article describes a case of follicular ameloblastoma involving 45 year old male which is different from the usual presentation, which includes-exophytic growth, different location and without expansion of the cortex. PMID- 21977483 TI - Payment reform: it's time to get real! PMID- 21977482 TI - The Ability of PAS, Acetylsalicylic Acid and Calcium Disodium EDTA to Protect Against the Toxic Effects of Manganese on Mitochondrial Respiration in Gill of Crassostrea virginica. AB - Manganese (Mn) is an essential metal that at excessive levels in brain causes Manganism, a condition similar to Parkinson's disease. Previously we showed that Mn had a neurotoxic effect on the dopaminergic, but not serotonergic, innervation of the lateral ciliated cells in the gill of the Eastern Oyster, Crassostrea virginica. While the mechanism of action of Mn toxicity is not completely understood, studies suggest that Mn toxicity may involve mitochondrial damage and resulting neural dysfunction in the brain's dopaminergic system. In this study we utilized micro-batch chambers and oxygen probes to measure oyster gill mitochondrial respiration in the presence of Mn and potential Mn blockers. The addition of Mn to respiring mitochondria caused a dose dependent decrease in mitochondrial O(2) consumption. Pretreating mitochondria with calcium disodium EDTA (caEDTA), p aminosalicylic acid (PAS) or acetylsalicylic acid (ASA) before Mn additions, provided full protection against the toxic effects of Mn. While mitochondrial pretreatment with any of the 3 drugs effectively blocked Mn toxicity, none of the drugs tested was able to reverse the decrease in mitochondrial O(2) consumption seen in Mn treated mitochondria. The study found that high levels of Mn had a toxic effect on gill mitochondrial O(2) consumption and that this effect could be blocked by the drugs caEDTA, PAS and ASA. C. virginica continues to be a good model with which to investigate the mechanism that underlies manganese neurotoxcity and in the pharmacological study of drugs to treat or prevent Manganism. PMID- 21977484 TI - Removing barriers to insulin use. AB - Patients with type 2 diabetes and their physicians are often reluctant to begin insulin therapy--despite evidence of its efficacy. Here's help in overcoming this other form of "insulin resistance." PMID- 21977485 TI - Elbow injuries: getting kids back in the game. AB - Elbow injuries are increasingly common in children and young adults who participate in team sports nearly year-round. This review--and the tables that accompany it--can help you help them safely return to play. PMID- 21977486 TI - Dyspnea, pancytopenia, and splenomegaly. AB - An extensive initial laboratory assessment, including testing for viral disorders, left the diagnosis unsolved. PMID- 21977487 TI - Supine infant positioning--yes, but there's more to it. AB - The Back-to-Sleep campaign has helped reduce the incidence of SIDS, but a neglect of prone positioning during wakefulness has increased the risk of 3 complications. PMID- 21977488 TI - PURLs: arthritis pain? These supplements provide little relief. AB - Taken alone or together, these 2 supplements don't relieve the pain of hip or knee osteoarthritis. PMID- 21977489 TI - Pruritic erythematous maculopapular rash. AB - A trip to the beach left this patient with an unusual rash where his bathing suit had been. PMID- 21977490 TI - Clinical inquiry. Are serum uric acid levels always elevated in acute gout? AB - Many patients with acute gout (11%-49%) have normal serum uric acid (SUA) levels. PMID- 21977491 TI - Clinical inquiry. What is the most effective way to treat recurrent canker sores? AB - Amlexanox appears to be most effective overall. Amlexanox 5% paste reduces ulcer size, pain duration, and healing time. PMID- 21977492 TI - Clinical inquiry. Chronic urticaria: what diagnostic evaluation is best? AB - Chronic urticaria affects 1% of the general population and is usually defined as the presence of hives (with or without angioedema) for at least 6 weeks.1 PMID- 21977493 TI - Clinical inquiry. Postcholecystectomy diarrhea: what relieves it? AB - A trial of a bile acid binder such as cholestyramine or colestipol may benefit patients with postcholecystectomy diarrhea. PMID- 21977494 TI - Detection of hydrogen peroxide in rainwater based on Mg-Al-carbonate layered double hydroxides-catalyzed luminol chemiluminescence. AB - Using a green catalyst of luminol chemiluminescence (CL), Mg-Al-carbonate layered double hydroxides (denoted as Mg-Al-CO(3) LDHs), a novel, sensitive and rapid CL method was developed for the determination of hydrogen peroxide (H(2)O(2)). The corresponding linear regression equation was established in the range of 0.05-10 MUM for H(2)O(2). The detection limit (S/N = 3) is 0.02 MUM and the relative standard deviation (RSD) for nine repeated measurements of 1.0 MUM H(2)O(2) was 2.9%. This proposed method has been successfully applied to detect H(2)O(2) in rainwater samples with good accuracy and precision. The novel methodology is expected to provide a general protocol for the determination of H(2)O(2) as well as for numerous other oxidase-based reactions giving H(2)O(2) as a product (e.g., glucose). PMID- 21977495 TI - Electrochemical chip integrating scalable ring-ring electrode array to detect secreted alkaline phosphatase. AB - An electrochemical platform for parallel monitoring of secreted alkaline phosphatase (SEAP) has been microfabricated on a device with a mammalian-cell array chip. A 4 * 4 ring-ring electrode array was designed at the rim of the round cellular pattern with a diameter of 270 MUm. Electrochemical characterization was carried out, and it was found that the collection efficiency was about 50% in dual mode when the inner-ring and the outer-ring electrodes were selected as the collector and generator electrodes, respectively. The current amplification ratio for the dual mode normal to single mode was 2.84. SEAP expressing from the cells was parallelly monitored by using a multiplexer switching system at the 16 round cellular spots. The reduction current for HeLa cells transfected with plasmid encoding SEAP observed at the collector outer ring electrode was found to be significantly higher than that for wild-type HeLa. Finally, the top of the microwell with the round cellular pattern was covered with a poly(dimethylsiloxane) block for 5 min to accumulate the secreted enzyme and the product of the enzyme reaction so that further signal enhancement could be observed. PMID- 21977496 TI - Abstracts of Asian Pacific Digestive Week. October 1-4, 2011. Singapore. PMID- 21977497 TI - Abstracts of the Society for Social Medicine 55th Annual Scientific Meeting. September 14-16, 2011. Warwick, United Kingdom. PMID- 21977498 TI - Abstracts of the SAPC (Society for Academic Primary Care) Annual Conference 2011. July 6-8, 2011. Bristol, United Kingdom. PMID- 21977499 TI - Abstracts of the 25th European Health Psychology Conference. September 20-24, 2011. Hersonissos, Crete, Greece. PMID- 21977500 TI - Some like it toxic. AB - Humans are notorious for disturbing terrestrial ecosystems worldwide, especially those that are in close proximity to urban areas. This disturbance has involved the accumulation of various types of chemical pollutants, of either agricultural or industrial origins, in both soil and water ecosystems. Pollutants have sometimes included essential plant nutrients, such as phosphate and nitrate, which have piled up throughout the years in many ecosystems as a consequence of aggressive agricultural practices, and a number of toxic or trace metals, e.g. iron, nickel or zinc that are important at low levels for the fitness of living organisms, but otherwise toxic at high concentrations (Ker & Charest 2010; Audet & Charest 2008). In order to reduce the load of toxic elements, scientists have used the natural capacity of several plant species to sequestrate them from the soil and, ultimately, render them harmless. This process, called phytoremediation, is rather slow, as most plants take years to build up their biomass but has been shown to be 'boostable' under experimental conditions in the presence of a particular group of plant symbionts in the soil - the arbuscular mycorrhizal fungi (AMF) (Gohre & Paszkowski 2006). These latter organisms are now widely recognized as being very beneficial for purposes of phytoremediation, but their biodiversity in the most disturbed ecosystems is still virtually unknown. Are these fungi really abundant in heavily polluted soils, or are their communities shrunken down like those of other microorganisms in the presence of heavy pollution? In this issue of Molecular Ecology, the study by Hassan et al. (2011) provides answers to these specific questions by determining the extent of AMF biodiversity across several urbanized areas in the City of Montre'al. PMID- 21977501 TI - The inner membrane subassembly of the enteropathogenic Escherichia coli bundle forming pilus machine. PMID- 21977502 TI - Abstracts of the International Society for Heart and Lung Transplantation Thirty First Annual Meeting and Scientific Sessions. April 13-16, 2011. San Diego, California, USA. PMID- 21977503 TI - Abstracts of the 16th Neurogastroenterology & Motility Meeting. September 16-18, 2011. St Louis, Missouri, USA. PMID- 21977504 TI - Huge pseudo-aneurysm of right ventricular outflow tract after patch reconstruction in tetralogy of Fallot. PMID- 21977505 TI - Demonstration of a right circumflex aortic arch with aberrant left subclavian artery and a hypoplastic arch by multi-detector computer tomography. PMID- 21977506 TI - Sporis, G, Vucetic, V, Jovanovic, M, Jukic, I, and Omrcen, D. Reliability and factorial validity of flexibility tests for team sports: method paper. J Strength Cond Res 25: 1168-1176, 2011. PMID- 21977507 TI - [Babylonic confusion]. PMID- 21977508 TI - [A second term psychosis]. PMID- 21977509 TI - The stigma of tuberculosis. PMID- 21977510 TI - A left frontal cystic mass. PMID- 21977511 TI - Spastic paraplegia in a 4-year-old boy. PMID- 21977512 TI - One-stop shopping for HIV information and resources: the HIV case manager portal. PMID- 21977513 TI - From superfit to superfat. PMID- 21977514 TI - [Consultation in routine general practice - fuzzy logic in action]. PMID- 21977515 TI - Cytoplasmic motion induced by cytoskeleton stretching and its effect on cell mechanics. AB - Cytoplasmic motion assumed as a steady state laminar flow induced by cytoskeleton stretching in a cell is determined and its effect on the mechanical behavior of the cell under externally applied forces is demonstrated. Non-Newtonian fluid is assumed for the multiphase cytoplasmic fluid and the analytical velocity field around the macromolecular chain is obtained by solving the reduced nonlinear momentum equation using homotopy technique. The entropy generation by the fluid internal friction is calculated and incorporated into the entropic elasticity based 8-chain constitutive relations. Numerical examples showed strengthening behavior of cells in response to externally applied mechanical stimuli. The spatial distribution of the stresses within a cell under externally applied fluid flow forces were also studied. PMID- 21977516 TI - On tensegrity in cell mechanics. AB - All models are wrong, but some are useful. This famous saying mirrors the situation in cell mechanics as well. It looks like no particular model of the cell deformability can be unconditionally preferred over others and different models reveal different aspects of the mechanical behavior of living cells. The purpose of the present work is to discuss the so-called tensegrity models of the cell cytoskeleton. It seems that the role of the cytoskeleton in the overall mechanical response of the cell was not appreciated until Donald Ingber put a strong emphasis on it. It was fortunate that Ingber linked the cytoskeletal structure to the fascinating art of tensegrity architecture. This link sparked interest and argument among biologists, physicists, mathematicians, and engineers. At some point the enthusiasm regarding tensegrity perhaps became overwhelming and as a reaction to that some skepticism built up. To demystify Ingber's ideas the present work aims at pinpointing the meaning of tensegrity and its role in our understanding of the importance of the cytoskeleton for the cell deformability and motility. It should be noted also that this paper emphasizes basic ideas rather than carefully follows the chronology of the development of tensegrity models. The latter can be found in the comprehensive review by Dimitrije Stamenovic (2006) to which the present work is complementary. PMID- 21977517 TI - Fluctuating elastic filaments under distributed loads. AB - Filaments under distributed loads are common in biological systems. In this paper, we study the thermo-mechanical properties of an extensible thermally fluctuating elastic filament under distributed forces. The ground state of the filament is solved first, followed by an investigation of the thermal fluctuations around the ground state. We first consider a special case where the tangential component of the distributed force tau is uniform along the filament. For the force-extension relation in this case, we show that the filament is equivalent to one under end-to-end applied force F = tauL0/2 where L0 is the length of the filament. To study the thermal fluctuations under more general distributed loadings, the filament is first discretized into segments, and its energy is approximated up to quadratic order. Then the partition function of the discretized filament, or chain, is evaluated using multi-dimensional Gaussian integrals, from which free energy and other properties of the filament are derived. We show that a filament under distributed loads suffers larger thermal fluctuations than one with the end loads of the same magnitude. We also show that our results for a discretized filament agree with continuum theory for a continuous rod. Finally, we give some applications of our ideas to the stretching and fluctuation of DNA in non-uniform microfluidic channels. PMID- 21977518 TI - Effects of altered restraints in beta1 integrin on the force-regulated interaction between the glycosylated I-like domain of beta1 integrin and fibronectin III9-10: a steered molecular dynamic study. AB - Cytoskeletal restraints affect force-regulated integrin function in cell adhesion. However, the structural and molecular basis underlying the effect of cytoskeletal restraints on beta1 integrin binding to fibronectin is still largely unknown. In this study, we used steered molecular dynamics simulations to investigate the changes in glycosylated beta1 integrin-fibronectin binding and in conformation and structure of the glycosylated beta1 I-like domain-FN-III9-10 complex caused by altered restraints applied to beta1 I-like domain. The results revealed that imposition of the increased constraints on beta1 integrin increased resistance to force-induced dissociation of the beta1 I-like domain-fibronectin complex. Specifically, the increased constraints enhanced resistance to relative conformational changes in the RGD-synergy site in fibronectin, increased the conformational stability of fibronectin, and prevented losses in hydrogen bond occupancy of each beta-strand pair in FN-III10 resulting from external force. The increased constraints also resulted in an increase in correlated motion between residues in the beta1 I-like domain, which may directly affect the interaction of beta1 integrin with fibronectin. Results from this study provide molecular and structural insights into the effects of altered restraints in beta1 integrin on the interaction between glycosylated beta1 Integrin and fibronectin and its induced cell adhesion. PMID- 21977552 TI - [Traditionalism and the politics of cultural identity in Asia and the Pacific: a critical clarification]. PMID- 21977553 TI - Paper soldiers: the world of the soldier hero according to Soviet wartime posters. PMID- 21977554 TI - Pastoralism, patriarchy and history: changing gender relations among Maasai in Tanganyika, 1890-1940. PMID- 21977555 TI - Policing the savage: segregation, labor and state medicine in the Andamans. PMID- 21977556 TI - Pooterism or partnership? Marriage and masculine identity in the lower middle class, 1870-1920. PMID- 21977557 TI - Popular culture: from being an enemy of the "feminist movement" to a tool for women's "liberation"? PMID- 21977559 TI - Social and symbolic fathers and sons in postwar Britain. PMID- 21977558 TI - Sex, politics, and social change in the eighteenth and the nineteenth centuries: evidence from the Swiss Alps. AB - The eighteenth-century "sexual revolution" cannot simply be explained as a consequence of economic or institutional factors -- industrialization, agricultural revolution, secularization, or legal hindrances to marriages. The example of western Valais (Switzerland) shows that we have to deal with a complex configuration of factors. The micro-historical approach reveals that in the eighteenth- and nineteenth-century sexuality -- and above all illicit sexuality - was a highly subversive force that was considerably linked to political innovation and probably more generally to historical change. Nonmarital sexuality was clearly tied to political dissent and to innovative ways of behavior, both among the social elites and the common people. This behavior patterns influenced crucial evolutions in the social, cultural, and economic history of the region. PMID- 21977560 TI - [Social housing construction in Vienna: a historical assessment]. PMID- 21977561 TI - The internationalization of police: the DEA in Mexico. PMID- 21977562 TI - From cure chair to 'chaise longue': medical treatment and the form of the modern recliner. PMID- 21977563 TI - Himmler and the 'racially pure gypsies'. PMID- 21977564 TI - The benefits of breastfeeding for most newborns and infants cannot be overstated. PMID- 21977565 TI - Comparison of maternity care quality in teaching and non-teaching hospitals in Khorram Abad, Islamic Republic of Iran. AB - The objective of this study was to compare the quality of maternity care in 2 types of government-run hospital in the town of Khorram Abad, Islamic Republic of Iran in 2009: a university-linked teaching and a social security organization non teaching hospital. A sample of 264 women hospitalized in the delivery and postpartum wards was selected. Data collection was done using interviews with mothers and observation checklists based on Iranian government criteria. The quality of maternity care in the non-teaching hospital was higher than the teaching hospital in terms of facilities, processes of maternal and newborn care and outcomes (mother's satisfaction). In the teaching hospital, the quality of the physical space, the educational level and training of health care personnel and monitoring and evaluation of care quality needed improvement. In both hospitals, meeting women's expectations about the degree of privacy could lead to an increase in the quality of maternity services. PMID- 21977566 TI - Outcome of vaginal birth after caesarean section in women with one previous section and spontaneous onset of labour. AB - The data about the safety of vaginal birth after caesarean section are conflicting. This study in a referral hospital in Sana'a, Yemen investigated the outcome of vaginal birth after caesarean section in 357 women who had one prior caesarean section and were admitted to hospital at term with spontaneous onset of labour. A control group (n = 155) was matched from women without previous caesarean section. The success rate of vaginal birth after caesarean section was 311/357 (87.1%). The mean duration of the first and second stages of labour were not significantly different in the study group (146.2 and 30.7 min respectively) compared with the control group (146.7 and 29.8 min). There were infrequent complications; only 1 woman (0.3%) had ruptured uterus and 3 women (1.0%) suffered uterine dehiscence. There was 1 stillbirth after the uterine rupture but no maternal deaths. PMID- 21977567 TI - Reasons for cancellation of elective operations at a major teaching referral hospital in Jordan. AB - Cancellation of elective scheduled operations leads to an inefficient use of operating room time and a waste of resources. This prospective records-based study aimed to determine the rate of and reasons for cancellations of scheduled elective surgical operations in a major teaching referral hospital in Jordan. Over a period of 12 months, cancellation was recorded in 382 (3.6%) of 10 485 scheduled elective surgical operations. Day unit cancellations accounted for 27.5% and inpatient cancellations for 72.5%. Patient-related reasons, administrative and medical reasons accounted for 31.4%, 30.4% and 38.2% of all cancelled operations respectively. The most common patient-related reason for cancellation was patient non-attendance. The most common administrative reason for cancellations was unavailability of hospital admission beds. Although the cancellation rate was low in comparison with the reported rates worldwide, reductions might be achieved by adopting some important interventions, especially better bed utilization. PMID- 21977568 TI - Determining and prioritizing competencies in the undergraduate internal medicine curriculum in Saudi Arabia. AB - To determine knowledge and skills competencies in internal medicine for the undergraduate curriculum in Saudi Arabia, competencies were identified based on group work utilizing common textbooks. The Delphi Technique was used as a consensus method to determine and prioritize competencies in internal medicine. A group of 20 clinicians rated the identified competencies from 0-3 (0: no need to know, 1: interesting to know, 2: should know and 3: must know). After formulating the results, a second Delphi round was conducted with 5 experts in internal medicine. A total of 1513 knowledge competencies and 189 skills competencies were determined and prioritized. The competencies corresponded to the 12 systems in internal medicine. All competencies rated 2.2-3.0 were produced separately and considered core competencies for the undergraduate internal medicine curriculum. Determining and prioritizing competencies should influence the curriculum reform process. PMID- 21977569 TI - Evaluation of prophylactic antibiotic administration at the surgical ward of a major referral hospital, Islamic Republic of Iran. AB - We evaluated the appropriateness of antibiotic prophylaxis administered before surgery at a major referral hospital in Shiraz, against the American Society of Hospital Pharmacists (ASHP) guidelines. Data on surgical procedure, choice of antibiotic and administration were gathered for all surgeries performed on hospitalized patients during 15 days in March 2010. Of 155 patients included in the analysis, 98% received prophylactic antibiotic before surgery; according to ASHP guidelines, prophylaxis was needed in only 106 (68.4%). Of these 106, only 8 patients received the correct antibiotic regimen. The commonest regimens administered were cefazolin + gentamicin (47.6%), cefazolin (20.5%) and cefuroxime (8.5%). Antibiotic prophylaxis was continued in 83% of cases, while this was necessary in only 37%. In only 1 surgical procedure were all evaluated parameters correct. PMID- 21977570 TI - Peginterferon alfa-2b and ribavirin therapy in Kuwaiti patients with chronic hepatitis C virus infection. AB - Few studies have been conducted in the Eastern Mediterranean region on chronic hepatitis C virus (HCV) infection with reference to genotypes. We investigated the response to standard combination therapy (pegylated interferon/ribavirin) of different genotypes of HCV in Kuwaiti patients and factors that could be associated with sustained virological response (SVR). The records of all Kuwaiti patients treated for chronic HCV between January 2003 and May 2009 were retrospectively identified and reviewed. Of 108 patients studied, 27.8% were infected with genotype 1, 25.0% with genotype 3 and 47.2% with genotype 4. Overall, 64.8% of patients achieved SVR, 25.9%, were non-responders and 9.3% were relapsers. Baseline viral load and alanine aminotransferase level in addition to early virological response to pegylated interferon-based therapy may serve as a decision tool for clinicians to identify patients who are unlikely to achieve SVR. PMID- 21977571 TI - Cross-reaction of antigen preparations from adult and larval stages of the parasite Setaria equina with sera from infected humans with Wuchereria bancrofti. AB - Crude antigenic preparations from Setaria equina were used in ELISA and Western blotting to examine cross-reaction with human sera from areas endemic for bancroftian filariasis. Sera from normal subjects from non-endemic areas were included as negative controls. Cross-reaction was found between S. equina antigens and antibodies in the sera of Wuchereria bancrofti-infected patients, with the highest levels observed between sera of chronic infected patients and Setaria spp. crude female worm surface antigen (CFSWA). In the absence of active transmission of Setaria spp. infection, CFWSA is useful to detect chronic W. bancrofti infection before patients become symptomatic, particularly when chronic patients are known to be amicrofilaraemic. In the presence of active S. equina infection, antigens from the adult and microfilaraemic stages showed the highest degree of cross-reaction with human sera. PMID- 21977572 TI - Bone mineral density in Egyptian adolescents and adults with short stature: results of a national survey. AB - Little is known about bone mass acquisition among stunted adolescents who did not achieve their growth in height. A national survey was made of bone mineral density among stunted adolescents and adults. A multistage stratified random sample of 2500 families (8476 adolescents and their parents) was selected from 6 governorates in different geographical areas of Egypt. Clinical history, anthropometry and measurement of bone mineral density using dual energy X-ray absorptiometry was done. Mean T-scores were significantly lower among both adults and adolescents with short stature compared with those of normal height. The predictors of bone status among adolescent boys were age, body mass index (BMI), height attained (z-score) and maternal T-score and for girls were BMI, age at menarche, paternal T-score and z-score. Stunted adolescents suffered from low bone mass density and low stature adults suffered a high prevalence of osteoporosis. PMID- 21977573 TI - Physical activity profile of students in Mansoura University, Egypt. AB - A cross-sectional study was carried out on 1708 students from Mansoura University, Egypt, to describe the pattern of physical activity, predictors of physical inactivity and perceived barriers to and benefits of physical activity. The International Physical Activity Questionnaire (IPAQ) was used to measure physical activity. Data were analysed according to the guidelines for data processing and analysis of the IPAQ. Perceived barriers to and potential benefits of physical activity were asked for. More than 11% of students were physically inactive. On logistic regression analysis, the independent predictors of physical inactivity were high socioeconomic standard of the family (OR 2.1), female sex (OR 1.8), medical education (OR 1.8) and non-membership in sports clubs OR 1.6). The most frequent barriers to physical activity were time limitation and lack of accessible and suitable sporting places. More than 70% of the participants stated that physical activity promotes and maintains health. PMID- 21977574 TI - Medical education in Saudi Arabia: a review of recent developments and future challenges. AB - Medical education has been changing rapidly in Saudi Arabia. Within a decade, the number of medical colleges increased from 5 medical schools with traditional disciplined-based curricula to 21 medical colleges with varied curricula ranging from the traditional to more innovative, problem-based, community-oriented programmes. The private sector has started investing in higher education generally and medical education in particular. Also other government sectors that provide advanced health services have started established new medical colleges. The expansion of quantity in medical education has been associated with a drive for greater quality assurance. Accreditation of higher education institutes began with the establishment of the National Commission for Academic Assessment and Accreditation in 2005. This review focuses on documenting developments in Saudi medical education up to 2008 and discussing the future potential and challenges facing the sector. PMID- 21977575 TI - Etiological factors of constipation in the elderly, with emphasis on functional causes. AB - Constipation is a particularly troublesome complaint in the elderly yet it is usually considered to be a simple management issue. Therefore physicians' lack of interest in and inadequate training about the etiology of constipation may contribute to their inability to manage the problem of constipation effectively. Constipation can become a chronic problem, refractory to management, and most likely the result of lifelong patterns of bowel and dietary habits and laxative use, along with the interaction of pathophysiological and perhaps senescent changes of gut motility. This article reviews the types and causes of constipation and the management of the problem in the elderly. PMID- 21977576 TI - Using surveillance data for action: lessons learnt from the second generation HIV/AIDS surveillance project in Pakistan. AB - Although many countries are now collecting useful, high-quality HIV surveillance data, more efforts are put into the collection of data than into ensuring it is deployed effectively. The Canada-Pakistan HIV/AIDS surveillance project has strengthened and expanded the existing national AIDS control programme surveillance system in Pakistan through a comprehensive estimate of the size and location of some of the most at-risk populations (sex workers and injection drug users) and annual assessments of their sociodemographic characteristics, behaviours and HIV prevalence. The country now uses second generation surveillance data at a broad level to lobby for policy change, mobilize resources, improve programming and measure the success of prevention through an integrated national effort. This article aims to share the experiences and lessons learnt in the development of a second generation surveillance system for HIV/AIDS in Pakistan. PMID- 21977577 TI - Road rage behaviour and experiences of rickshaw drivers in Rawalpindi, Pakistan. AB - A cross-sectional survey with convenience sampling was conducted among rickshaw drivers in Rawalpindi, Pakistan to study their road rage behaviour and experiences. Cumulatively 318 male drivers participated in this study. The most common forms of road rage reported were: having been shouted at; and having experienced rude gestures from other drivers (78.9% each). Least common forms of road rage reported were: threats of physical hurt or having actually been physically hurt ( < or = 3% each). Rickshaw drivers with shorter driving time (< or = 10 years) had significantly more road rage experiences than those who had been driving for more than 10 years (P < 0.01). There is a need for nationally representative surveys to study road age in commercial vehicle drivers so as to improve road safety in Pakistan. PMID- 21977578 TI - Two cases of Vibrio cholerae non-O1/non-O139 septicaemia with favourable outcome in Lebanon. PMID- 21977579 TI - [Generation of recombinant human antibodies for EV71 virus]. AB - OBJECTIVE: To obtain recombinant human anti-EV71 antibodies from a EV71 associated hand-foot-and-mouth disease patient-derived antibody phage library. METHODS: A combinatorial human scFv library to enterovirus 71 (EV71) virus was constructed using antibody genes harvested from the blood of EV71 virus patients. The library was panned and selected by using purified VP1 protein of EV71 virus with phage display. After that the specific antibody was converted to full human IgG antibody with recombinant baculovirus/insect cell system. RESULTS: One unique human scFv antibody specific for EV71 virus VP1 protein was obtained by ELISA, IFA and analysis of the antibody DNA sequence. The specific anti-VP1 human scFv antibody was converted to full human IgG antibody with recombinant baculovirus/insect cell system. The full human IgG antibody was tested in vitro for EV71 virus neutralization, resulting in no neutralizing activity with EV71 A type and EV71 C4 subtype. CONCLUSION: The obtained human anti-EV71 antibodies without neutralizing activity laid the foundation for diagnosis of human EV71 associated hand-foot-and-mouth disease. PMID- 21977580 TI - [Mutations in various functional domains of HPV2 E2 protein inhibit the transcriptional depression activities]. AB - OBJECTIVE: To study the potential transcriptional depression activities of HPV2 E2 proteins with mutations in different functional domains. METHODS: The primers for constructing various E2 mutants were synthesized based on a HPV2 isolate containing several point mutations within E2 open reading frame. Different E2 mutations were generated by the method of extending PCR and inserted into plasmid pcDNA3. 1. Various recombinant mammalian expression plasmids pcDNA3. 1-E2 were co transfected into HeLa cells together with a CAT-reporter plasmid pBLCAT-LCR containing HPV-2 prototype LCR, respectively. The transcriptional repression activities of the E2 mutants were evaluated by detection of CAT expression values. RESULTS: Compared with the full-length prototype E2, removals of both N- and C-terminal domains abolished E2 transcriptional repressive activities. The point mutations in the transactivation domain (nt 3037), the internal hinge region (nt 3387) and DNA binding domain (nt 3697) showed remarkable inhibition on its transcriptional depression function. CONCLUSION: The transcriptional regulation activity of HPV2 E2 is related with its DNA binding and transactivation domains. The exchanges of the single amino acid within E2, derived from a HPV2 isolate, abolish significantly the repressive effect on viral promoter in the context of full-length E2. PMID- 21977581 TI - [Construction of vectors expressing M2 and NA genes of H5N1 influenza virus]. AB - OBJECTIVE: To construct vectors expressing M2 and NA genes of H5N1 influenza virus. METHODS: Based on the human H5N1 avian influenza virus (A/Anhui/1/2005) isolated in china, M2 and NA genes were amplified by PCR. M2 or NA gene was subcloned into pStar vector to construct recombinant pStar-M2/, pStar-/M2, pStar NA/and pStar-NA/. Furthermore, both of the M2 and NA genes were subcloned into pStar to construct two genes co-expressing recombinant pStar-M2/NA and pStar NA/M2. Expression of the genes were detected by IFA after transfection of 293 cells with the recombinant plasmids. RESULTS: Recombinant plasmids were constructed and identified by restriction endonuclease digestion. Expression of the genes cloned into the recombinant plasmids was confirmed by IFA. CONCLUSION: Recombinant plasmids expressing M2 and/or NA genes of H5N1 influenza virus were constructed, which provided basis for development of influenza DNA vaccine. PMID- 21977582 TI - [Construction and recovery of chimeric rabies virus expressing envelop proteins E1E2 of hepatitis C]. AB - OBJECTIVE: Construction and recovery of chimeric rabies virus expressing HCV envelop proteins E1E2. METHODS: On the basis of the previously established reverse genetic system CTN-GFP, HCV E1E2 genes were cloned to both replication competent and replication constrained viral vectors based on CTN181 strain and the chimeric viruses CTN-HCV E1E2 and CTNdeltaG-HCV E1E2 were recovered. RESULTS: The result demonstrated that both the chimeric viruses were rescued successfully, had the ability to re-infect normal sensitive cell lines and express HCV E1E2 genes detected in the level of mRNA. CONCLUSION: The establishment of chimeric RVs expressing HCV E1E2 genes provides the evidence that it is feasible to develop novel HCV vaccines based on viral vectors in theory and in practice. PMID- 21977583 TI - [Genetic evolution of VP1 of enterovirus type 71 in Shenzhen]. AB - OBJECTIVE: Genetic evolution of VP1 of enterovirus type 71 in Shenzhen were analyzed. METHODS: All samples were tested by RT-PCR using EV71 specific primer. The VP1 of EV71 were amplified and sequenced. A phylogenetic tree was constructed by comparison of the sequences with subgenotype A, B and C using DNAStar, BioEdit and Mega 3.1 software. RESULTS: Among 35 strains, the homogeneity of the VP1 nucleotide sequence was between 92.1%-100%. The homogeneity of the VP1 nucleotide sequence with subgenotype A and B was between 81.4% -91.1%. The VP1 nucleotide sequence of 35 strains of Shenzhen shared between 93% -97.4% identity with cluster C4. The prevalence strains of EV71 were cluster C4b from 1998 to 2004, and gradually moved to C4a since 2003. All of EV71 were C4b from 2006 to 2008. Also, the homogeneity of the VP1 nucleotide sequence with Anhui FY23 EV71 strain were 94.5% -94.7%, 95.7% -95.8%, 96.2%, 95.4% -97.5%, 96.3% -99.2% from 2003 to 2008. It shows that the homogeneity was increased year by year. There was a mutation (A --> C) at No. 66 nucleotide of VP1 of EV71 that two strains were isolated in 2003 and 8 strains in 2008, that caused amino acid mutation (Q --> H) at No. 22 of VP1. CONCLUSION: EV71 C4b was gradually moved to C4a from 1998 to 2008. There was a missense mutation at No. 66 nucleotide of VP1. PMID- 21977584 TI - [Autophagy inhibitor 3-MA decreases the production and release of infectious enterovirus 71 particles]. AB - OBJECTIVE: To determine whether or not enterovirus 71 (enteroviurs 71, EV71) may induce autophagy and affect the production and release of EV71 after the treatment of autophagy inhibitor. METHODS: Western blots were performed to examine the conversion of LC3-I to LC3- II and the degradation of P62 after the RD-A cells were infected with EV71. CCID50 was determined by checking the virus titer in the supernatant of cells that treated with autophagy inhibitor 3-MA. RESULTS: EV71 infection enhances the type conversion of LC3 and degradation of P62. The infectious virus particles were decreased after the treatment of 3-MA. CONCLUSION: EV71 infection could induce cell autophagy and the autophagy might contribute to the production and release of infectious EV71 particles. PMID- 21977585 TI - [Screening of the target genes transactivated by PS1TP1 protein with suppression subtractive hybridization technique]. AB - OBJECTIVE: To construct a subtractive cDNA library of genes transactivated by PS1TP1 protein with suppression subtractive hybridization (SSH) technique. METHODS: Suppression subtractive hybridization technique and bioinformatics technique were used, the mRNA from HepG2 cells transfected with pcDNA3.1 (-) PS1TP1 and pcDNA3. 1 (-) empty vector was isolated, respectively; cDNA underwent two times of nested PCR, amplified cDNA fragments were subcloned into pGEM-Teasy vectors to set up the subtractive library. RESULTS: The subtractive library of genes transactivated by PS1TP1 was constructed successfully. Sequence analysis was performed in 43 clones randomly, and the full length sequences were obtained with bioinformatics method and searched for homologous DNA sequence from GenBank, altogether 12 coding sequences were gotten, which consisted of 10 known and 2 unknown ones. CONCLUSION: The obtained sequences may be target genes transactivated by PS1TP1 protein among which some genes coding proteins involved in cell cycle regulation, metabolism, immunity and cell apoptosis. This finding brought some clues for studying the biological functions of PS1T1. PMID- 21977586 TI - [The studies for activating and inhibitory receptors on natural killer cells in HIV/HCV co-infected patients]. AB - OBJECTIVE: To investigate the characteristics of inhibitory and activating receptor expressions on natural killer (NK) cells in HIV/HCV co-infected patients. METHODS: Numbers, frequencies and expressions of activating and inhibitory receptors of NK cells were measured with flow cytometry (FCS) from HIV/HCV co-infected group (n = 24), HCV mono-infected group (n = 34), HIV mono infected group (n = 21) and healthy control group (HC, n = 20), then analysis and compare were performed among those groups. RESULTS: The NK cell absolute counts in HIV/HCV group were significantly lower than those in other three groups. The NKP30 and NKP46 frequencies on NK cells in HIV/HCV, HIV and HCV groups were all significantly lower than those in HC group, but there were no significant differences of NKP30 among former three groups; and NKP46 frequencies in HIV/HCV and HIV groups were lower than those in HCV group, but there were no significant differences between former two groups. The NKG2A frequencies in HIV/HCV and HCV groups were all higher than those in HIV and HC groups significantly, but the NKG2A frequencies in HIV group were lower than those in HC group; There were no significant differences of NKG2D, CD158a and CD158b among those four groups. CONCLUSION: NK cell numbers and expressions of activiting receptors on NK cells obviously decreased in HIV/HCV co-infected patients, but some inhibitory receptors expressions increased, even higher than those of HIV mono-infected patients. NK cells impairments in HIV/HCV co-infection is more severe than HIV or HCV mono-infection. PMID- 21977587 TI - [The study on significance of detecting the hepatitis B virus large proteins in public health physical examination]. AB - OBJECTIVE: It was to explore the application of the hepatitis B virus large proteins (HBV-LP) in public health physical examination through clinical testing of HBV-LP in Catering practitioners, students and soldiers of New requisition etc. METHODS: 709 samples of HBV infection people were collected in public health physical examination and all collected samples were detected. ELISA was used to detect HBV serum markers (HBV-M) and HBV-LP. Real-time PCR was applied to detect quantity of HBV DNA. RESULTS: (1) The detectable results of HBV-LP and HBV DNA were no statistical significance in 709 samples. (2) The detectable results of HBV-LP and HBV DNA were also no statistical significance in different models of HBV infection patients. The values of chi2 and P were respectively 2.67, 0.60, 0.00 and 0.10, 0.44, 1.00. S/A of HBV-LP and the copies of HBV-DNA had a positive relationship (r = 0.959, P < 0.05). CONCLUSION: HBV-LP could reflect the level of hepatitis B virus replication and be used to judge the level of hepatitis B virus replication in people of public health physical examination. HBV-LP may be worth using widely in physical examination. PMID- 21977588 TI - [Effects of human cytomegalovirus on the cell cycle of duct epithelial cell cultures of human salivary gland in vitro and relative mechanism]. AB - OBJECTIVE: To investigate the effects of human cytomegalovirus (HCMV) on the cell cycle of duct epithelial cell cultures of human salivary gland (HSG) in vitro and relative mechanism. METHODS: HSG was cultured in vitro. Reverse transcriptase polymerase chain reaction (RT-PCR) and nest-RT-PCR were used respectively to investigate ie1/ie2 transcription in HSG infected by human cytomegalovirus(HCMV). The effects of HCMV on the cell cycle of HSG were studied by flow cytometry in vitro. The expression of cyclin D1 in HSG infected by HCMV was detected by Western blotting. RESULTS: HCMV iel/ie2 transcription could be detected in HSG infected by HCMV. HCMV arrested productively infected cells in G1 stage. And cyclin D1 was down-regulated in HCMV infected HSG. CONCLUSION: HCMV inhibits proliferation of HSG by affecting G1/S check point and down-regulating cyclin D1 in vitro. PMID- 21977589 TI - [Adsorption of virus onto ionic surfactants of polypropylene fibers]. AB - OBJECTIVE: To provide better laboratory protection material in virology lab to prevent laboratory accident infection. METHODS: The four kinds of ionic polypropylene fibers were constructed and interact with recombinant adenovirus expressing GFP. Both the GFP expression and hexon gene expression of recombiant adenovirus were used to evaluate absorb ability of fibers. RESULTS: Both the amphoteric and iron ionic polypropylene fibers have certain adsorption or inactivated ability to virus in 5 min, the other two fibers decreased the growth within 20 min. CONCLUSION: Both the amphoteric and iron ionic polypropylene fibers can be used as laboratory protection material in virology lab. PMID- 21977590 TI - [The structure and function analysis of duplicate genes in Merlin strains of human cytomegalovirus]. AB - OBJECTIVE: To determine the genes in which exist overlapping ORF in Merlin strains of human cytomegalovirus, and to reveal their structure and functional characteristics. METHODS: We search for overlapping genes of ORF in HCMV Merlin strains' whole genome by Bioinformatics methods, analyzing coding sequence CDS and starting and ending sites of ORF, calculating the length of CDS and ORF, analyzing the molecular weight of encoding protein, overlapping length and coding direction of protein, identifying overlapping sequences and overlapping types, analyzing the expression phase of overlapping genes and the function of proteins. RESULTS: There were 39 overlapping ORF genes in HCMV Merlin strains, accounting for 23% of total genes. Among these 39 genes, there are 13 IE genes, 9 E genes and 17 L genes, which can be divided into 16 contigs. There are 11 contigs when two genes overlap, with 3 contigs in three genes overlapping, and 2 contigs in four genes overlapping. The functions of overlapping genes are widely. CONCLUSION: We found that there are a lot of complex overlapping genes in HCMV Merlin strains, which are basis for further study of the transcription and translation mechanism of overlapping genes. PMID- 21977591 TI - [Immunogenicity of sabin inactivated poliovirus vaccine induced by diphtheria tetanus-acellular pertussis and Sabin inactivated poliovirus combined vaccine]. AB - OBJECTIVE: In order to search the preparation process and optimazing dosage ratio of adsorbed diphtheria-tetanus-acellular pertussis and sabin inactivated poliovirus combined vaccine (DTaP-sIPV), the neutralizing antibody titers of IPV induced by different concentration of DTaP-sIPV were investigated on rats. METHODS: Two batches of DTaP-sLPV were produced using different concentration of sIPV and the quality control was carried. Together with sabin-IPV and DTaP-wIPV ( boostrix-polio, GSK, Belgium) as control group, the DTaP-sIPV were administrated on three-dose schedule at 0, 1, 2 month on rats. Serum sample were collected 30 days after each dose and neutralizing antibody titers against three types poliovirus were determined using micro-neutralization test. RESULTS: Two batches of prepared DTaP-sIPV and control sLPV were according to the requirement of Chinese Pharmacopoeia (Volume III, 2005 edition) and showed good stability. The seropositivity rates were 100% for sabin inactivated poliovirus antigen in all groups. The GMTs (Geometric mean titers) of neutralizing antibodies against three types poliovirus increased. CONCLUSION: The prepared DTaP-sIPV was safe, stable and effective and could induced high level neutralizing antibody against poliovirus on rats. PMID- 21977592 TI - [Detection and the antibiotic susceptibility analysis of mycoplasma and chlamydia in urogenital tract infections of 327 cases patients with tubal infertility]. AB - OBJECTIVE: To explore the effects of mycoplasma and chlamydia infections on tubal infertilityand to assess the antibiotic susceptibility and resistance of female urogenital, and consequently to guide clinical rational drug use. METHODS: 327 tubal infertility women as infertility group and 286 healthy pregnant women as control group were randomly selected, detected chlamydia trachomatis (CT), ureaplasma urealyticum (UU) and mycoplasma hominis (MH) in cervical secretions and drug resistance of UU and MH. RESULTS: CT infection rates (14.99%), UU infection rates (23.24%), UU + MH infection rates (29.05%),CT + UU + MH infection rates (9.17%) and total infection rates (88.99%) in infertility group is higher than those (order: 2.80%, 6.99%, 8.39%, 4.55%, 29.02%) in the control group, comparisons of two groups are statistically significant differences (P < 0.05), the susceptibility of UU to roxithromycin (sensitivity is 96.05%), josamycin (sensitivity is 96.05%), tetracycline (sensitivity is 82.89%), vibramycin( sensitivity is 92.11%) and clarithromycin (sensitivity is 96.05%) were relatively high and low to ciprofloxacin and acetyl spiramycin. The susceptibility of MH to josamycin (sensitivity is 95.83%), vibramycin (sensitivity is 91.67%), minocin (sensitivity is 83.33%) and actinospectacin (sensitivity is 75.00%) were relatively high and low to erythromycin, azithromycin, roxithromycin and clarithromycin. UU + MH was only sensitive to josamycin (sensitivity is 90.52%), high resistance (77.89% -91.58%) to erythromycin, azithromycin, acetyl spiramycin, ciprofloxacin, ofloxacin, azithromycin and clarithromycin. CONCLUSION: Infection of CT, UU, MH and tubal infertility have certain relevance,the rates of CT, UU and MH infection in tubal infertility patients higher than fertile people. For many commonantibacterial drugs, UU, MH and UU + MH has strong resistance, the etiology detection and using adapted antibios should be taken seriously in clinical treatment. PMID- 21977593 TI - [The proliferation of H1N1 subtype influenza viruses in A549 and BEAS-2B cells]. AB - OBJECTIVE: Analyze the proliferation of different host H1N1 subtype influenza viruses in A549 and BEAS-2B cells. METHODS: Human, avain and swine three hosts of the H1N1 influenza viruses infected A549 and BEAS-2B cells and analyze the characteristics of different periods after inocubation. Determine the receptor binding specificity of influenza virus by hemagglutination (HA) test with RBCs with two types of receptor. And the receptors on surfaces of A549 and BEAS-2B cells were tested by flow cytometry. RESULTS: The Cell Pathologic Effect (CPE) is obvious after 24 h inoculation in A549 cells by all the H1N1 influenza viruses, moreover, the peak hemagglutinin (HA) and 50% tissue culture cell infected dose (TCID50) titers was observed after 36 h of culturing in A549 cells. Otherwise, the CPE is not typical from 24 h-120 h inoculated by the same viruses and the HA, TCID50 titers were keep low all the periods in the BEAS-2B cell after inoculation. The receptor-binding preference of H1N1 viruses used in the study was screened by HA assay and some were found with 2-6-receptor binding affinity. Both SA a-2, 3Gal and SA a-2, 6Gal receptors were detected on A549 and BEAS-2B, furthermore, receptor density on A549 cells was significantly higher than that of BEAS-2B cells. CONCLUSION: A549 cells were susceptible to human, avian and swine H1N1 influenza viruses infection and permissively for viral replication. However, BEASE-2B cells with similar receptor pattern and epithelium-derived propriety as A549 cells were unsusceptible to their infection and replication. Possible host factors involved in effective viral infection and replication were needed further study. PMID- 21977594 TI - [Analysis of drug-resistant multi-loci mutation of P area of HBV genome in 32 patients with chronic hepatitis B]. AB - OBJECTIVE: In order to deeply understand the effects of nucleoside analogues to HBV DNA polymerase area, which initiate a state of drug resistance due to HBV genome mutation. METHODS: Using PCR product direct sequencing method to test the gene sequence of P area of HBV genome of the patients who taking nucleoside analogues and showing signs of virologic breakthrough. RESULTS: More resistance mutations can be find in HBV DNA polymerase area, which causing clinically cross drug resistance and multiple resistance. CONCLUSION: We should choose higher genetic barrier for the initial treatment. And the patients long-term using of nucleoside analogues, should be regularly monitored serum HBV DNA level, in order for early detection of virological breakthrough and timely intervention. PMID- 21977595 TI - [Relationship between viral genotype and specific and nonspecific CTL of patients with cirrhotic hepatitis B and its significance]. AB - OBJECTIVE: To explore relationship between different HBV genotypes and peripheral blood HBV specific and nonspecific CTL of patients with cirrhotic hepatitis B and its significance. METHODS: HBV genotypes were tested in 91 patients with cirrhotic hepatitis B, differences of HBV specific and nonspecific CTL between patients infected with genotype B and C were compared and its significance was explored. RESULTS: In 91 cases of cirrhotic hepatitis B, 55 cases (60.44%) belong to genotype C, 35 cases (38.46%) belong to genotype B, 1 case (1.1%) belongs to mixture genotype B and C. In genotype C, 27 cases (49.09%) had positive (HLA)-A2, HBV specific CTL was 0.18% +/- 0.03%. In genotype B, 18 cases (51.43%) had positive HLA-A2, HBV specific CTL was 0.38% +/- 0.04%, higher than that in genotype C, t = 5.01, P < 0.01. Nonspecific CTL: genotype C (11.87% +/- 1.50%); genotype B (11.90% +/- 1.51%), t = 0.14, P < 0.05. HBV DNA level: genotype C (6.01 +/- 0.81) log10 copy/ml, higher than that in genotype B (5.01 +/- 0.54) log10 copy/ml, t = 5.01, P < 0.01. ALT: genotype C (251.13 +/- 131.11) U/L, higher than that in genotype B (121.25 +/- 63.21) U/L, t = 3.61, P < 0.01. TBil (45.61 +/- 15.11) micromol/L, higher than that in genotype B (28.11 +/- 6.25) micromol/L, t = 3.05, P < 0.01. CONCLUSION: Compared with patients infected with genotype B of cirrhotic hepatitis B, HBV specific CTL of patients infected with genotype C was lower, resulting in higher level of HBV DNA and more severe damage of liver function. PMID- 21977596 TI - [Association of liver histopathology and clinical features among patients with chronic hepatitis B virus infection]. AB - OBJECTIVE: To explore the histopathological features of chronic hepatitis B virus (HBV) carriers and chronic hepatitis B (CHB) patients with mildly elevated serum alanine aminotransferase (ALT). METHODS: 105 patients were divided into three groups according to serum ALT levels: Group A [ALT level < or = 0.5 x upper limits of normal (ULN)], Group B (0.5 x ULN < ALT level < or = 1 x ULN) and Group C(1 x ULN < ALT level < 2 x ULN). Grade of liver inflammation and stage of liver fibrosis in the three groups were compared. The changes in clinical parameters were then observed in patients who had liver histopathological changes. RESULTS: Among 40.95% of the patients, hepatitis degree went to G2 or even worse; and among 30.43% of the patients whose ALT level were normal, the hepatitis degree reached G2 or even worse. In 26.67% of the patients, degree of fibrosis went to S2 or even worse, and for the 17.39% patients whose ALT level were normal, degree of fibrosis went to S2 or even worse. The aggravation of liver inflammation and fibrosis was correlated with ALT and hyaluronic acid increasing (all P < 0.05). CONCLUSIONS: Frequent monitoring of serum ALT and hyaluronic acid may help to understand histopathological changes in the liver. Liver biopsy applied to CHB should be regarded as a main basis if antiviral therapy should be conducted. PMID- 21977597 TI - [Clinical analysis in viral encephalitis patients accompanying generalized tonic clonic seizure]. AB - OBJECTIVE: To summarize the value of clinical features, CSF, imaging and EEG in diagnosing viral encephalitis accompanying generalized tonic clonic seizure (GTCS). METHODS: The clinical, imaging and EEG characteristic of 30 patients with viral encephalitis accompanying GTCS were retrospectively analyzed. RESULTS: Of the 30 cases with viral encephalitis, 21 cases GTCS attacked (70%) within 14 days, 9 cases had GTCS (30%) in 15-28 days. 27 cases CSF were abnormal with the pressure, cell number, protein. The incidence of positive pathogenicity was 12/16; 19 cases MRI had abnormal signal. All the patients had abnormal EEG during the disease. CONCLUSION: The clinical features, CSF, imaging and EEG were all important in diagnosing and estimate of viral encephalitis accompanying GTCS. PMID- 21977598 TI - [Relationship between HBeAg seroconversion with genotypes and HBV specific CTL in patients with chronic hepatitis B treated with Adefovir dipivoxil]. AB - OBJECTIVE: To explore relationship between HBeAg seroconversion with HBV genotypes and HBV specific CTL in patients with chronic hepatitis B (CHB) treated with Adefovir dipivoxil. METHODS: Seventy CHB patients had positive HBV DNA (HBV DNA > or = 1 x 10(4) copy/ml), 45 cases had positive HBeAg, of whom 23 cases (51. 11%) had genotype B, 22 cases (48.89%) had genotype C. ALT > 2 x upper limit of normal value (ULN), human leukocyte antigen (HLA)-A(n) positive, patients were treated with Adefovir dipivoxil (commercial name is Mingzheng, Zhengda Tianjing Pharmaceutical Company), 10 mg, orally, once a day. After treatment for 12 months, observe relationship between HBeAg seroconversion with HBV genotypes and HBV specific CTL. RESULTS: After treatment with Adefovir dipivoxil for 12 months, HBV specific CTL (0.68% +/- 0.11%) was higher than that before treatment (0.33% +/- 0.11%), t = 8.36 P < 0.001, HBV DNA (3.01 +/- 0.2) log10 copy/ml was lower than that before treatment (6.27 +/- 0.70) log10 copy/ml, t = 12.63 P < 0.001, HBV DNA turned negative (< 500 copy/ml) 43 cases (61.43%), in 45 cases with positive HBeAg, HBeAg turned negative in 13 cases (28.89%), 8 cases had HBeAg seroconversion (17.78%), HBV specific CTL (0.86% +/- 0.05%) of patients with HBeAg seroconversion is higher than (0.61% +/- 0.07%) of patients without HBeAg seroconversion (37 cases, 82.22%) t = 7.88, P < 0.001. In 8 cases with HBeAg seroconversion, 7 cases had genotype B (30.43% of genotype B), 1 cases had genotype C (4.55% of genotype C), chi2 = 5.15, P < 0.05. CONCLUSION: Adefovir dipivoxil can enhance HBV specific cellular immunity of CHB patients. After treatment, occurrence of HBeAg seroconversion is related to increase of HBV specific CTL level and may be related to genotypes. PMID- 21977599 TI - [Clinical report on 68 cases of refractory mycoplasma pneumoniae pneumonia (RMPP)]. AB - OBJECTIVE: To summarize the early diagnose and treatment approaches of Refractory Mycoplasma Pneumoniae Pneumonia (RMPP). METHODS: Medical documents of 68 cases of RMPP were reviewed. Lab and radiology evident such as CBC, CRP, MP-IgM, X-ray, etc. were collected. RESULTS: 100% RMPP patients suffered from high fever. Positive sign of lung became clear with the development of the disease. Complications as impairment of liver function, cardiac function and rush developed in few patients. 2-4 rounds treatment of macrolides and Methyllprednisolone were necessary for RMPP while antibiotic may be considered when there were evidence of bacteria infection. Immunoglobulin was recommended to the patients when macrolides and steroid seemed ineffective. Bronchofibroscope played an active role regarding the diagnosis and treatment of RMPP. CONCLUSION: Early diagnosis is crucial in RMPP. Combination of multitreatment approaches is the key to cure RMPP. PMID- 21977600 TI - [A exploration and study of the relationships of hand-foot-mouth disease (HFMD) and the climate]. AB - OBJECTIVE: To explore and study the relationships between the popularity of HFMD and the climate in Qinhuangdao city. METHODS: HFMD cases were collected on a ten day basis in 2009 in Qinhuangdao city. At the same time, the data about Qinhuangdao's ten-day average temperature and average humidity were provided by the Qinhuangdao Meteorological bureau. Then the collected data were analysed using the great data analysis function in the EXCELE software. RESULTS: The results showed that the disease of HFMD had a positive relationship with seasons. The cases of HFMD began to rise at the last ten days of March and rised dramatically at the middle ten days of April; In July, the cases of HFMD arrived at peak and then decline gradually. The cases of HFMD in October were quite similar to the cases of HFMD in March. Then in November, the cases of HFMD declined rapidly. All these evidences suggested that the peak seasons of HFMD were Spring and Summer. CONCLUSION: The situations of HFMD had a significant positive relationship with the conditions of climate, such as high temperature and high humidity. PMID- 21977601 TI - [Preparation and application of a novel HCV diagnostic antigen fused to streptavidin]. AB - OBJECTIVE: To prepare streptavidin-tagged hepatitis C virus (HCV) fusion protein and explore its application for the detection of antibody against HCV infection. METHODS: A recombinant plasmid pET-11d-C44P-SA was constructed, which coding a novel HCV diagnostic antigens (C44P) and streptavidin (SA) fusion protein, and the fusion protein was generated with BL21 (DE3) E Coli and identified by Western Blot analysis. Then the fusion protein was purified through the Ni-NTA affinity chromatography and over 90% purity has been achieved. Anti-HCV ELISAs were developed when the fusion protein was used in the biotin-pre-coated microplate or ordinary microplate, and then the sensitivity and specificity of the ELISA were evaluated with confirmed human sera panels. RESULTS: The fusion protein was expressed in high yields and purified successfully, the ELISA detection of anti HCV with human sera panel indicated that its sensitivity and specificity is higher when SA-tagged HCV antigen (C44P-SA) coated in biotin-pre-coated microplate, compared to C44P or C44P-SA coated in ordinary microplate. CONCLUSION: The sensitivity and specificity of anti-HCV ELISA can be improved when a novel HCV diagnostic antigen fused to SA combined with the biotin- pre coated microplate. This study laid a foundation for improving the performance of HCV diagnostics. PMID- 21977602 TI - [Prevalence of depression and anxiety in a cohort of 761 obese patients: impact in adherence to therapy and its outcome]. AB - OBJECTIVE: To determine the prevalence of psychiatric disorders in 761 obese patients, prospectively assessing their impact in both adherence to therapy and its outcome. MATERIAL AND METHODS: Overweight and obesity were defined by body mass index (BMI), depression and anxiety according to "The Hospital Anxiety and Depressio Scale". Patients received a physical and biochemical evaluation, a hypochaloric diet and a training plan. Sibutramine was prescribed as anti-obesity drug. RESULTS: The mean age was 31,28 (SD 11,26) years. 74.77% were women. The mean weight was 91.36 kg with a BMI of 34,49 Kg/m2 (SD 6,29). The prevalence of possible, probable and definite anxiety/depression was: 56.3%/22.0%, 29.8%/6.2%, and 7.2%/0.8% respectively. Both initial and final weight and BMI were higher in definite and probable depression respectively, with a minor percentage of weight loss likewise. CONCLUSIONS: The studied psychiatric disturbances were prevalent in our population. Initial and final weight and BMI were higher in groups with more severe anxiety or depression. The percentage of weight loss and adherence to therapy were greater in groups of milder psychiatric disorders. PMID- 21977603 TI - [Risk minimization evolution of agranulocytosis caused by the administration of pharmaceutical products containing Clozapine in Argentina]. AB - Clozapine is an antipsychotic medication used in the treatment of schizophrenia. Compared to other drugs, Clozapine has shown remarkable advantages. However, its use entails a serious risk of causing hematologic alterations (including granulocytopenia/agranulocytosis). Such alterations may result in death if they are not detected early. Clozapine was recalled from the worldwide market and it was reintroduced some years later, but a mandatory hematologic monitoring program was implemented. The program was established in Argentina by ANMAT's regulation 935/00. It helped to monitor of the use of the drug. Currently, the incidence of agranulocytosis in our country is lower than the international incidence rates. PMID- 21977604 TI - [Evolutionary issues in attention deficit hyperactivity disorder (ADHD); from risk factors to comorbidity and social and academic impact]. AB - Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood disorders and at least one-third to one-half will continue through adolescence and adulthood. Moreover it is important the high comorbidity not only in children, but in adolescents and adults. Therefore ADHD becomes especially important when we observe it as a risk factor for the development of another psychopathology that add more complexity to the diagnosis of children and adolescents and also adults, and confers an evolutionary risk throughout the lifetime of the person who suffers from it. A correlational study with a sample of 378 patients diagnosed with ADHD in the childhood between 1988 and 2000 who had initiated treatment after been diagnosed was carried out. 88 patients were evaluated years after (2006) with ages between 18 and 33 years old. 85% of the patients in this study had had combined treatment. The data found in this study show lower comorbidity than other published studies (36.4%), as well as a lower persistence of the complete diagnosis of ADHD in the adulthood (15%). This is a treated population; the results may lead to a possible protector role of the early treatment of ADHD. PMID- 21977605 TI - [Adolescents psychiatric hospitalization younger than 17 years: complexity of the problematic and the resolution]. AB - Emotional pathology in adolescents is usually a problematic which involves thus adolescents and their environment, from its genesis, as in the time to evaluate resolution strategies. This concept led us to attempt to evaluate how much the family context modifies the decision to the hospitalization or not of the patient in crisis. Psychopathological variables were examined and family characteristics with the aim to find factors which associated. PMID- 21977606 TI - [Neurocognitive function in child and adolescent psychopathology]. AB - Executive control processes, such as sustained attention, response inhibition and working memory allows us to guide behavior appropriately, flexible and adaptable. The consequences of executive dysfunction in humans can be dramatic, as evidenced by the wide range of neurological and neuropsychiatric disorders in which such deficits impact negatively on the performance and quality of life, affecting high prosecutions relating to the prefrontal areas and their connections, including cognitive function. This review is to update and highlight the importance of assess neuropsychological and neurocognitive functional changes that occur in the course of various neuropsychiatric disorders in children and adolescents. PMID- 21977607 TI - [The severe dysregulated child. Clinical research]. AB - The term severe pathology of mood and behaviors includes a wide range of clinical presentations. A nosographic entity which is not clearly defined, the defiance is to search for scales that identify, using the same core phenotype, the patients with Emotional Dysregulation or Bipolar Spectrum Disorders. The Child Behavior Check List (CBCL) and their subscales seem to be helpful in identifying severe psychopathology of childhood, characterized by affective, behavioral and cognitive dysregulation. The family background and medical comorbidity (abnormal thyroidprofile) seem to be related to special entity diagnosed by the clinician. PMID- 21977608 TI - [Autism spectrum disorders. Functional-emotional development hypotheses and their relationship with therapeutic interventions]. AB - Autism Spectrum Disorders do not have a treatment that offers definitive solution to the serious challenges faced by people who suffer from them. Consequently, as in other chronic conditions, many therapeutic interventions are offered, each based on different neurobiological or psychological hypotheses. In the present article criteria for the organization of the proposed interventions are suggested, and the main aspects of the affective diathesis hypothesis are summarized. This theory emphasizes the importance of emotional signaling as a basis for development and is the theoretical framework for one of the therapeutic options in the field of autism that is earning recognition in our country: the DIR-Floortime model. PMID- 21977609 TI - [Suicide attempt in the adolescence: a clinical report]. AB - The aim of this paper is to communicate the job in a psychiatric inpatient unit based on the narration and analysis of an adolescent's suicide attempt. We insist on a personalized approach from an individual, familiar, and group point of view and the arrangement of treatment following discharge; all these from a therapeutic community's psychodynamic perspective. The work in the acute hospitalization is focused on the patient's recovery and returning to the community. PMID- 21977610 TI - [Sante de Sanctis: the first descriptions of child psychoses]. PMID- 21977611 TI - [Clinical patterns of dementia praecox in infancy and childhood. 1909]. PMID- 21977612 TI - [Dementia praecox. 1925]. PMID- 21977613 TI - Addressing parental concerns about vaccination. PMID- 21977614 TI - Chemical policy reform--nurses must say "yes"! PMID- 21977615 TI - Mercy provides health ed for 800,000 youth. PMID- 21977616 TI - Taming toxicity: reversing negativity in the workplace. PMID- 21977617 TI - Could you recognize a modern slave. PMID- 21977618 TI - Relationships behind closed doors: healthy work environments in the PACU. PMID- 21977619 TI - The necessity of sharing how evidence-based medicine works. PMID- 21977620 TI - Work continues as Iowa prepares to implement health reform. PMID- 21977621 TI - Health plan denials--Iowa's revised and expanded law effective July 1. PMID- 21977622 TI - Can we make Iowa the healthiest state? PMID- 21977623 TI - IBM mandates pain CME and urges use of prescription drug monitoring program. PMID- 21977624 TI - Diagnostic errors due to follow-up system failures. PMID- 21977625 TI - Elaboration of the hydroxyapatite with different precursors and application for the retention of the lead. AB - Carbonate hydroxyapatite (CHAP) was synthesized from different precursors; synthetic (CaCO3 and Ca(OH)2) and natural (egg shell before and after calcinations at 900 degrees C) under different conditions and characterized by using TG/DTG analysis, X-ray powder diffraction (XRD) method and Fourier transform infrared (FT-IR) spectroscopy techniques. The results of these analyses indicate that the four powders present the same structure of hydroxyapatite. Furthermore the four powders obtained were used for the retention of lead. The results obtained indicated that all powders present high adsorption capacity for lead, but from environmental and economic views, the hydroxyapatite synthesized from eggshell no calcined (HA2) is most advantageous. The influence of different sorption parameters, such as: initial metal concentration, equilibration time, solution pH and sorbent dosage was studied and discussed. PMID- 21977626 TI - Biofiltration as pre-treatment to water harvesting and recycling. AB - This paper presents the results of the long term biofilter experiments conducted with raw stormwater collected from a canal at Carlton, in Sydney. Anthracite and granular activated carbon (GAC) were used as a single filter media in biofilter columns. Media heights of 75 and 40 cm were used. The filter columns were operated at filtration velocities of 0.12 and 0.25 m/h. The removal efficiency for turbidity and DOC for the GAC filter media were found to be 75% and almost 100% respectively. The removal efficiency for the anthracite filter was much lower. Molecular weight distribution analysis showed an almost similar trend to the DOC removal. Compared with anthracite filter media, the GAC biofilter removed a much larger range of organic compounds present in the stormwater. The GAC biofilter removes organic matter earlier as compared to anthracite. Based on a limited sample of stormwater, the removal efficiency for phosphorus was upto 74% and that of nitrogen was up to 30%. In general GAC filter shows higher heavy metal removal efficiency than anthracite. The removal of zinc, iron, lead and nickel were good. However the concentration of heavy metal in the raw surface water sample was low. PMID- 21977628 TI - Sorption behavior of florisil for the removal of antimony ions from aqueous solutions. AB - Florisil was employed for the sorption of antimony ions from aqueous solutions. A detailed study of the process was performed by varying the sorption time, pH, and temperature. The sorption was found to be fast, equilibrium was reached within 15 min. Moreover, a maximum sorption has been achieved from solution when the pH ranges between 1-10. From kinetic experiments it follows that the process correlate with the second-order kinetic model. The overall rate process appears to be influenced by both boundary layer diffusion and intra-particle diffusion. The Langmuir and Dubinin-Radushkevich (D-R) type sorption isotherms can be applied to fit and interpret the sorption data. The mean energy of adsorption (9.73 kJ mol(-1)) was calculated from the Dubinin-Radushkevich (D-R) adsorption isotherm at room temperature. Furthermore, the thermodynamic parameters for the sorption were also determined, and the deltaH0 and deltaG0 values indicate a spontaneous endothermic behavior. PMID- 21977627 TI - Adsorption of four perfluorinated acids on non ion exchange polymer sorbents. AB - Perfluorinated compounds (PFCs) have attracted global concern due to their ubiquitous distribution and properties of persistence, bio accumulation and toxicity. The process of adsorption has been identified as an effective technique to remove PFCs in water. Different non ion-exchange polymeric adsorbents were tested with regard to their sorption kinetics and isotherms at low PFCs concentrations. Selected PFCs were perfluorobutanoic acid (PFBA), perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) and the tested polymers were three types of Dowex optopores (V-493, V503, and L493), Amberlite XAD-4, and Filtrasorb 400 (Granular Activated Carbon-GAC). We observed the selective adsorption of PFCs on synthetic polymers. For PFDA, Amberlite XAD-4 gave the Freundlich adsorption constant of 2,965 (microg PFCs/g sorbent)(microg PFCs/L)(-n), which was higher than that of GAC (121.89 (microg PFCs/g sorbent) (microg PFCS/L)(-n)). In the case of PFBA, GAC showed better performance (13.36) (microg PFCs/g sorbent) microg PFCS/L)(-n) than synthetic polymers (0.62-5.23) (microg PFCs/g sorbent) (microg PFCS/L)(-n). Adsorption kinetics of all adsorbents were well described (R2 = 0.85-1) by pseudo second order kinetic model. Sorption capacity was influenced by initial PFCs concentration for all adsorbents. GAC reached the equilibrium concentration within 4 hours, Amberlite XAD 4 reached it within 10 hours and other polymers took more than 70 hours. PMID- 21977629 TI - Ozone-based reclamation of an STP effluent. AB - The system ozone and hydrogen peroxide was used to reclaim wastewater from the secondary clarifier from a Sewage Treatment Plant (STP) of Alcala de Henares (Madrid-Spain). The assays were performed by bubbling a gas mixture of oxygen and ozone, with approximately 24 g Nm(-3) of ozone concentration, through a volume of wastewater samples for 20 minutes at 25 degrees C. The removal of dissolved micropollutants such as Pharmaceutical and Personal Care Products (PPCPs) and Organic Carbon (TOC) was enhanced by adding periodic pulses of hydrogen peroxide while keeping pH above 8.0 throughout the runs. Removal efficiency ratios in the range of 7-26 mg O3/mg TOC and 0.24 mg O3/ng micropollutants at 5 minutes of ozonation were assessed as reference data to reclaim wastewater from STP. The relation between the extent of TOC removed and ozone doses used was related by a second-order kinetic model in which the time-integrated ozone-hydrogen peroxide concentration was included. PMID- 21977630 TI - Comparison of Fenton's oxidation and ozonation for removal of estrogens. AB - This study compares efficiency of Fenton's oxidation and ozonation of 17beta estradiol (E2) and 17alpha-ethinylestradiol (EE2) as two possible processes for removal of estrogens from aqueous solutions. The effectiveness of Fenton's oxidative removal was studied at different ratios of reagents Fe2+:H2O2 (1:0.5; 1:10; 1:20; 1:33), where with some molar ratios up to 100% removal of E2 and EE2 was achieved in the first few minutes of reaction. The best molar ratio for E2 (17beta-estradiol) removal was 1:33, while in the case of EE2 the most efficient one was 1:20 ratio. Ozonation was much faster, because complete removal of estrogens was achieved in 30 seconds (pH approximately eaqual 6), but the time of ozonation was extended up to 60 minutes trying to decompose formed by-products, expressing estrogenic activity, detected by YES (Yeast Estrogen Screening) assay. The obtained results showed that the removal efficiency of estrogens from waters should be assessed by a combination of chemical analyses and bioassay. PMID- 21977631 TI - Application of reversed A2/O process on removing nitrogen and phosphorus from municipal wastewater in China. AB - The application of reversed A2/O process in practice in China is mainly discussed in this paper. As a new process on nitrogen and phosphorus removal, principle and technical features of reversed A2/O process are also summarized. The application in rebuilt wastewater treatment plant shows that reversed A2/O process not only has merits on high nitrogen and phosphorus removal efficiency, but also has merits on energy saving. The application in newly-build wastewater treatment plant shows that infrastructure and equipment investment of reversed A2/O process economized 15% and 10% respectively, compared to conventional A2/O process. The practical application shows that reversed A2/O process is a new nitrogen and phosphorus removal process, which is suitable for China's national conditions. PMID- 21977632 TI - Presence and risk assessment of pharmaceuticals in surface water and drinking water. AB - Trace amounts of pharmaceuticals have been detected in surface waters in the nano to microgram per liter range, and in drinking water in the nanogram/L range. The environmental risks of pharmaceuticals in surface waters have been evaluated and generally found to be low if the wastewater is treated before release to the environment. The human health risks of trace amounts of pharmaceuticals in drinking water have however not been evaluated in any great depth. Preliminary screening level assessments suggest risk to be low--but the public and decision makers are concerned and would like the matter investigated more thoroughly, especially with regards to mixture effects, chronic long-term effects and sensitive sub-populations. The World Health Organization is currently evaluating the need for credible health based guidance associated with low concentrations of pharmaceuticals in drinking water. The aim of this paper is to summarize the state-of-the-science and the ongoing international debate on the topic. PMID- 21977633 TI - Pilot scale evaluation of SANI process for sludge minimization and greenhouse gas reduction in saline sewage treatment. AB - This study reports on a pilot trial of the SANI process (Sulfate reduction, Autotrophic denitrification and Nitrification Integrated process) in Hong Kong. A pilot-scale SANI plant treating saline sewage at 10 m3/day was scaled-up from a lab-scale system treating synthetic saline sewage. The plant consisted of a sulfate reduction up-flow sludge bed (SRUSB), an anoxic bioreactor (BAR1) for autotrophic denitrification utilizing dissolved sulfide produced by the SRUSB and an aerobic bioreactor (BAR2) for nitrification. The SANI pilot plant was successfully operated for 225 days and achieved average COD, TSS, TN removal of 87, 87, and 57%, respectively. The ratio of MLVSS to MLSS in the SRUSB was stable at 0.7 and the average sludge volume index (SVI) was constantly below 110 ml/g. No sludge was purposely withdrawn from the plant during 225-day plant operation. This was attributed to a very low observed sludge yield (0.02 kgVSS/kgCOD removed) of the SRUSB reactor. DNA extraction, PCA amplification results revealed that no methanogens were detected in the SRUSB. SANI can reduce 90% sludge production, 35% energy and 36% GHG compared to conventional biological nutrient removal (CBNR) process. PMID- 21977634 TI - Improved environmental multimedia modeling and its sensitivity analysis. AB - Modeling of multimedia environmental issues is extremely complex due to the intricacy of the systems with the consideration of many factors. In this study, an improved environmental multimedia modeling is developed and a number of testing problems related to it are examined and compared with each other with standard numerical and analytical methodologies. The results indicate the flux output of new model is lesser in the unsaturated zone and groundwater zone compared with the traditional environmental multimedia model. Furthermore, about 90% of the total benzene flux was distributed to the air zone from the landfill sources and only 10% of the total flux emitted into the unsaturated, groundwater zones in non-uniform conditions. This paper also includes functions of model sensitivity analysis to optimize model parameters such as Peclet number (Pe). The analyses results show that the Pe can be considered as deterministic input variables for transport output. The oscillatory behavior is eliminated with the Pe decreased. In addition, the numerical methods are more accurate than analytical methods with the Pe increased. In conclusion, the improved environmental multimedia model system and its sensitivity analysis can be used to address the complex fate and transport of the pollutants in multimedia environments and then help to manage the environmental impacts. PMID- 21977635 TI - Activated sludge modelling: development and potential use of a practical applications database. AB - This study aims at synthesizing experiences in the practical application of ASM type models. The information is made easily accessible to model users by creating a database of modelling projects. This database includes answers to a questionnaire that was sent out to model users in 2008 to provide inputs for a Scientific and Technical Report of the IWA Task Group on Good Modelling Practice Guidelines for use of activated sludge models, and a literature review on published modelling projects. The database is analysed to determine which biokinetic model parameters are usually changed by modellers, in which ranges, and what values are typically used for seven selected activated sludge models. These results should help model users in the calibration step, by providing typical parameter values as a starting point and ranges as a guide. However, the proposed values should be used with great care since they are the result of averaging practical experience and not taking into account specific parameter correlations. PMID- 21977636 TI - Determination of odorous VOCs and the risk of occupational exposure to airborne compounds at the waste water treatment plants. AB - Concentrations of non methane-VOCs and risk levels of employees' exposure to VOCs were determined at two Finnish waste water treatment plants. The concentration of hydrogen sulphide (H2S) reached the Finnish OEL (occupational exposure limit). The concentrations of styrene, 1,2-dichloroethane, and toluene were found to be elevated at plant A. 328.4 microg/m3 of styrene and 709.8 microg/m3 toluene was found in the sludge dewatering, and 955.8 microg/m3 of 1,2-dichloroethane was detected in the trash rake. TVOC concentrations varied from 149.8 microg/m3 in the Plant B sludge dewatering to 7719.0 microg/m3 in the Plant A sludge dewatering. Most of the detected TVOC concentrations were quite high in comparison to the indoor air regulations or recommendations. The most odorous compounds were determined by combined TD-GC-MS-sniffing analysis. Odour was mainly caused by sulphur-containing compounds, aldehydes, and butanoic acid, in addition to aromatic compounds such as styrene, toluene and 4-methylphenol. PMID- 21977637 TI - Field investigation of arsenic in ceramic pot filter-treated drinking water. AB - Ceramic pot filters (CPFs) is one of several household water treatment technologies that is used to treat drinking water in developing areas. The filters have the advantage of being able to be manufactured using primarily locally available materials and local labor. However, naturally-occurring arsenic present in the clay used to make the filters has the potential to contaminate the water in excess of the World Health Organization drinking water standard of 0.01 mg/L. A manufacturing facility in Guatemala routinely rinses filters to reduce arsenic concentrations prior to distribution to consumers. A systemic study was performed to evaluate the change in arsenic concentrations with increasing volumes of rinse water. Arsenic field kit results were compared to standard method laboratory results, and dissolved versus suspended arsenic concentrations in CPF-treated water were evaluated. The results of the study suggest that rinsing is an effective means of mitigating arsenic leached from the filters, and that even in the absence of a formal rinsing program, routine consumer use may result in the rapid decline of arsenic concentrations. More importantly, the results indicate that filter manufacturers should give strong consideration to implementing an arsenic testing program. PMID- 21977638 TI - Application of the Morris method for screening the influential parameters of fuzzy controllers applied to wastewater treatment plants. AB - In this paper, we evaluate the application of a sensitivity analysis to help fine tuning a fuzzy controller for a biological nitrogen and phosphorus removal (BNPR) plant. The Morris Screening method is proposed and evaluated as a prior step to obtain the parameter significance ranking. First, an iterative procedure has been performed in order to find out the proper repetition number of the elementary effects (r) of the method. The optimal repetition number found in this study (r = 60) is in direct contrast to previous applications of the Morris method, which usually use low repetition number, e.g. r = 10 - 20. Working with a non-proper repetition number (r) could lead to Type I error (identifying a not-important factor as significant (false positive)) as well as Type II error (identifying an important factor as not significant (false negative)), hence emphasizing the importance of finding the optimal repetition number for each study in question. With the proper r found, the Morris Screening helped identify the parameter significance ranking, thereby facilitating the calibration of fuzzy controllers, which contain many parameters that need to be adjusted for different wastewater treatment plant (WWTP) applications. PMID- 21977639 TI - Multivariate analysis of the transport in an ion exchange membrane bioreactor for removal of anionic micropollutants from drinking water. AB - The present study focuses on investigating the effects of biological compartment conditions on the transport of nitrate and perchlorate in an Ion Exchange Membrane Bioreactor (IEMB). In this hybrid process, the transport depends not only on the membrane properties but also on the biological compartment conditions. The experiments were planned according to the Plackett-Burman statistical design in order to cover a broader range of experimental conditions, under which a previously developed mechanistic transport model was not able to predict correctly the transport fluxes of the target pollutants. Using Principal Component Analysis, it was possible to identify not only the concentrations of target (nitrate and perchlorate) and of major driving counter-ion (chloride) but also those of some biomedium components (e.g. ammonia, ethanol and sulphate) as variables that affect the transport rate of micropollutants across the membrane. These conclusions are based on the loadings of the two first principal components that describe 84% of the data variance. The present study also revealed that the hydraulic retention time and the hydrodynamic conditions in the biocompartment have a minor contribution to the micropollutants transport. The results obtained are important for process optimization purposes. PMID- 21977640 TI - Overview of municipal sludge fluid bed incineration in North America--from green to greener--the Lakeview, the Duffin Creek and the Southerly experiences. AB - Thermal processes used in sludge disposal have become more attractive as process improvements have been introduced, such as power generation and efficient heat recovery. More and more utilities and agencies are reevaluating their sludge management practices to ensure that they are providing sustainable management solutions for their clients. The thermal process design approach to the disposal of sludge is not only designed to achieve stricter emission limits but also is more energy efficient compared to its predecessors. Increasing numbers of new plants are being built every year with more energy efficient heat recovery features such as air preheating and cogeneration with steam and electricity production. This paper presents an overview of fluid bed incineration in North America and its evolution over the last decades. Case studies of the last three newest and largest plants in North America are presented, including the Lakeview Plant, Duffin Creek Plant, both in Ontario, Canada and the Southerly Plant in Cleveland, Ohio, USA. PMID- 21977641 TI - Assessing the convergence of LHS Monte Carlo simulations of wastewater treatment models. AB - Monte Carlo (MC) simulation appears to be the only currently adopted tool to estimate global sensitivities and uncertainties in wastewater treatment modelling. Such models are highly complex, dynamic and non-linear, requiring long computation times, especially in the scope of MC simulation, due to the large number of simulations usually required. However, no stopping rule to decide on the number of simulations required to achieve a given confidence in the MC simulation results has been adopted so far in the field. In this work, a pragmatic method is proposed to minimize the computation time by using a combination of several criteria. It makes no use of prior knowledge about the model, is very simple, intuitive and can be automated: all convenient features in engineering applications. A case study is used to show an application of the method, and the results indicate that the required number of simulations strongly depends on the model output(s) selected, and on the type and desired accuracy of the analysis conducted. Hence, no prior indication is available regarding the necessary number of MC simulations, but the proposed method is capable of dealing with these variations and stopping the calculations after convergence is reached. PMID- 21977642 TI - Prediction of scour below submerged pipeline crossing a river using ANN. AB - The process involved in the local scour below pipelines is so complex that it makes it difficult to establish a general empirical model to provide accurate estimation for scour. This paper describes the use of artificial neural networks (ANN) to estimate the pipeline scour depth. The data sets of laboratory measurements were collected from published works and used to train the network or evolve the program. The developed networks were validated by using the observations that were not involved in training. The performance of ANN was found to be more effective when compared with the results of regression equations in predicting the scour depth around pipelines. PMID- 21977643 TI - Sources and leaching of manganese and iron in the Saigon River Basin, Vietnam. AB - High concentrations of manganese and iron in the Saigon River are major problems for the water supply in Ho Chi Minh City (HCMC), Viet Nam. To identify their sources and leaching processes, we surveyed water quality along the Saigon River and ran batch leaching tests using soil and sediment samples. Two important leaching processes were identified: acidic leaching from acid sulfate soil (ASS) in the middle reaches of the river, and Mn dissolution and Fe reduction from sediments in the downstream reaches. Low pH caused the concurrent release of Fe and Mn from the ASS. In contrast, anoxia caused the release of Fe but not Mn from the sediments, whereas low pH facilitated Mn dissolution. Sediments are a more important source of Mn because of their higher Mn contents (10 times) and release rates (14 times) than those from ASS. PMID- 21977644 TI - Seasonal influence on urban dust PAH profile and toxicity in Sydney, Australia. AB - Road dust is one of the major threats to the urban environment due to wash-off of dust to the surrounding catchments during wet weather period. The dust contains wide range of toxic contaminants such as heavy metals, polycyclic aromatic hydrocarbons (PAHS) and endocrine disrupting chemicals. Among the toxic contaminants, PAHs are of environmental concern due to their potential carcinogenic and mutagenic effect besides endocrine disruptive behaviour. Eighteen road dust samples from Sydney were collected in different time periods for a year and analysed for 16 US EPA PAHS. Total PAHs content range in the dust was 9-105 pg/g. Total and individual PAH contents were highest in the finest size fraction (<75 microm) and in winter compared to the other seasons. The PAH profiles in the different particle sizes were similar but different between the four seasons. The concentrations of higher molecular weight PAHS (4- and 5-rings) were much greater than the concentrations of lower molecular weight PAHs (2- and 3-rings). Toxicity equivalency factor application showed that the longer the dry weather period the higher the total PAHs content and toxicity in the dust. PMID- 21977645 TI - Comparison of microbial activity in anaerobic and microaerobic digesters. AB - Microaerobic alternative of anaerobic digestion offers many advantages especially when sulfide concentration in the digester is high. For better understanding of the microaerobic technology more detailed characterization of biomass activity is needed. Two equal digesters were operated under the same condition except of microaeration in one of them. During long term operation of anaerobic and microaerobic digesters the sludge quality and the biomass activity was monitored. The activity of sulfide oxidizing bacteria of microaerobic biomass was significantly higher in comparison with anaerobic biomass. The activity of sulfate reducing bacteria was comparable. The activity of methanogenic bacteria activity depended on sulfide concentration more than on microaeration. The extent of foaming problems was lower in the microaerobic than in the anaerobic digester. PMID- 21977646 TI - Impact of sludge retention time on sludge characteristics and microbial community in MBR. AB - In this study, the impact of sludge retention time (SRT) on sludge characteristics and microbial community and the effect on membrane fouling in membrane bioreactor (MBR) was investigated. The results show that MBR with longer SRT has less fouling propensity, in agreement with other studies, despite the fact that the MBR with longer SRT contained higher MLSS and smaller particle size. However, much more soluble microbial products (SMPs) were released in MBR with shorter SRT. More slime on the membrane surface was observed in MBR with shorter SRT while sludge cakes formed on the membrane surface in MBR with longer SRT. The results show that SMP contributes to the severe fouling observed in MBR with shorter SRT, which is in agreement with other studies showing that SMPs were the major foulants in MBR. Under different SRTs of operation, the bacterial community structures of the sludge obtained by use of polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE) were almost identical, but those on the membrane surface differed substantially. It suggests that, although SRT has impact on sludge characteristics, it doesn't affect the microbial community in the suspension. PMID- 21977647 TI - Simulation and optimization of an experimental membrane wastewater treatment plant using computational intelligence methods. AB - The optimization of relaxation and filtration times of submerged microfiltration flat modules in membrane bioreactors used for municipal wastewater treatment is essential for efficient plant operation. However, the optimization and control of such plants and their filtration processes is a challenging problem due to the underlying highly nonlinear and complex processes. This paper presents the use of genetic algorithms for this optimization problem in conjunction with a fully calibrated simulation model, as computational intelligence methods are perfectly suited to the nonconvex multi-objective nature of the optimization problems posed by these complex systems. The simulation model is developed and calibrated using membrane modules from the wastewater simulation software GPS-X based on the Activated Sludge Model No.1 (ASM1). Simulation results have been validated at a technical reference plant. They clearly show that filtration process costs for cleaning and energy can be reduced significantly by intelligent process optimization. PMID- 21977648 TI - Integrated process control for recirculating cooling water treatment in the coal chemical industry. AB - This work focused on the integrated process of the recirculating cooling water (RCW) treatment to achieve approximate zero emission in the coal chemical industry. The benefits of fractional and comprehensive RCW treatment were quantified and qualified by using a water and mass balance approach. Limits of cycle of concentrations and some encountered bottlenecks were used to ascertain set target limits for different water sources. Makeup water was mixed with water produced from reverse osmosis (RO) in the proportion of 6:4, which notably reduced salts discharge. Side infiltration, which settled down suspended solids, can reduce energy consumption by over 40%. An automated on-line monitoring organic phosphorus inhibitor feed maintains the RCW system stability in comparison to the manual feed. Two-step electrosorb technology (EST) instead of an acid feed can lead cycle of concentration of water to reach 7.0. The wastewater from RO, EST and filter was transferred into a concentration treatment system where metallic ions were adsorbed by permanent magnetic materials. Separation of water and salts was completed by using a magnetic disc separator. Applying the integrated process in a coal chemical industry, a benefit of 1.60 million Yuan annually in 2 years was gained and approximate zero emission was achieved. Moreover, both technical and economic feasibility were demonstrated in detail. PMID- 21977649 TI - A flexible modelling environment for integrated urban water harvesting and re use. AB - The steady increase of urban population and the possible effects of climate change that may adversely affect the amount of water available in current water supply systems, makes the study of stormwater and rainwater harvesting and wastewater recycling a high priority. The basic proposition is that any system of water supply that can reduce the amount of water drawn from main reservoirs will be of benefit to the whole supply region especially in terms of drought security. This paper describes a versatile modelling framework which can simulate a wide variety of combinations of centralised and decentralised Integrated Urban Water Management schemes from the allotment to the whole suburb scale. The framework combines two modelling approaches. The first, called urbanCycle, simulates water supply and demand, stormwater and wastewater using allotments as the basic building block. Although urbanCycle can simulate processes in great detail, it assumes that the network forms a directed acyclic graph. This simplifies the connectivity logic but precludes investigation of systems with decentralised storage, feedbacks and multiple supply paths. To overcome this, a second model, called urbanNet, based on network linear programming, is embedded in the urbanCycle framework to enable the modelling of recycling and harvesting options, as well as on-the-fly supply and demand decision making, based on objectives rather than pre-set operating rules. PMID- 21977650 TI - Evaluation of two stormwater infiltration trenches in central Copenhagen after 15 years of operation. AB - Two stormwater infiltration trenches were installed in 1993 in an area in central Copenhagen. The system was monitored continuously for almost three years after establishment, and a small reduction in performance over that time, possibly due to clogging, was noted. A new study was conducted in 2009 to see whether the reduction in performance has continued and to determine how the system performs today. Water levels in the trenches were monitored for almost 4 months, and from this period seven events were selected to analyse the infiltration rate. A comparison with similar analyses on storm sequences from the first 3 years of operation shows that the infiltration has decreased since the establishment of the system 15 years ago. The decrease is statistically significant (p<0.01). A clogging model was fitted to the data and predictions were made for future performance. The results show that the system will discharge around 10 times more annual overflow to the sewers after 100 years of operation compared to the initial volumes, if clogging continues at current rates. This corresponds to 60% of the total runoff from the area. The results show that clogging and proper maintenance are important factors to consider when implementing stormwater infiltration trenches. PMID- 21977651 TI - A real-time control strategy for separation of highly polluted storm water based on UV-Vis online measurements--from theory to operation. AB - 'Classical' real-time control (RTC) strategies in sewer systems are based on water level and flow measurements with the goal of activation of retention volume. The control system rule of 'clean (storm water) runoff into the receiving water - polluted runoff into the treatment plant' has been thwarted by rough operating conditions and lack of measurements. Due to the specific boundary conditions in the city of Wuppertal's separate sewer system (clean stream water is mixed with polluted storm water runoff) a more sophisticated--pollution-based- approach was needed. In addition the requirements to be met by the treatment of storm water runoff have become more stringent in recent years. To separate the highly-polluted storm water runoff during rain events from the cleaner stream flow a pollution-based real-time control (P-RTC) system was developed and installed. This paper describes the measurement and P-RTC equipment, the definition of total suspended solids as the pollution-indicating parameter, the serviceability of the system, and also gives a cost assessment. A sensitivity analysis and pollution load calculations have been carried out in order to improve the P-RTC algorithm. An examination of actual measurements clearly shows the ecological and economic advantages of the P-RTC strategy. PMID- 21977652 TI - A new sewage exfiltration model--parameters and calibration. AB - Exfiltration of waste water from sewer systems represents a potential danger for the soil and the aquifer. Common models, which are used to describe the exfiltration process, are based on the law of Darcy, extended by a more or less detailed consideration of the expansion of leaks, the characteristics of the soil and the colmation layer. But, due to the complexity of the exfiltration process, the calibration of these models includes a significant uncertainty. In this paper, a new exfiltration approach is introduced, which implements the dynamics of the clogging process and the structural conditions near sewer leaks. The calibration is realised according to experimental studies and analysis of groundwater infiltration to sewers. Furthermore, exfiltration rates and the sensitivity of the approach are estimated and evaluated, respectively, by Monte Carlo simulations. PMID- 21977653 TI - Runoff infiltration, a desktop case study. AB - The use of sustainable drainage systems (SuDS) or best management practice is becoming increasingly common. However, rather than adopting the preferred 'treatment train' implementation, many developments opt for end-of-pipe control ponds. This paper discusses the use of SUDS in series to form treatment trains and compares their potential performance and effectiveness with end-of-pipe solutions. Land-use, site and catchment characteristics have been used alongside up-to-date guidance, Infoworks CS and MUSIC to determine whole-life-costs, land take, water quality and quantity for different SuDS combinations. The results presented show that the use of a treatment train allows approaches differing from the traditional use of single SuDS, either source or 'end-of-pipe', to be proposed to treat and attenuate runoff. The outcome is a more flexible solution where the footprint allocated to SUDS, costs and water quality can be managed differently to fully meet stakeholder objectives. PMID- 21977654 TI - Development of polymer lab-on-a-chip (LOC) for oxidation-reduction potential (ORP) measurement. AB - Reverse osmosis (RO) desalination has been recognized as a promising method to solve the water shortage problem. Nevertheless, since it is energy intensive and has many problems associated with biofouling/fouling of RO membranes in RO plants, its commercial acceptance is still slow. Especially, as high levels of oxidizing agents negatively affect RO membrane efficiency and life span. So, there is a need to develop sensitive, selective, portable and rapid methods to determine oxidation-reduction potential (ORP) in feed solution. For developing a polymer ORP lab-on-a-chip (LOC), a microchannel patterned on a polymer substrate was successfully filled with 800 nm diameter silica beads using self-assembly bead packing technology. The measured ORPs using the three kinds of redox potential solutions were typically slightly lower than those of the nominal redox potential. But, all of the measurements should be deemed acceptable. The ORP LOC has also a much shorter response time than the conventional potentiometric sensor. PMID- 21977655 TI - Effect of sludge retention time on characteristics of dynamic membrane in sequencing bioreactors. AB - The characteristics of self-forming dynamic membrane (DM) in sequencing bioreactors under different sludge retention times (SRT) (SRT = 5, 10, 20, 40, 60 days) were studied using a scanning electron microscope, particle sizing distribution and others. The results indicated that the SRT has an evident effect on the characteristics of DM. The content of extracellular polymeric substances and protein decreased with the increase of SRT. The change of polysaccharide was small regardless of SRT. The filtration resistance of the DM was divided into two stages: an initial slowly-rising stage and a fast-rising later stage which were both irrespective of SRT. With the increase of SRT, the filtration resistance increase extent reduced and the running cycle became longer. Compared to the lower SRT, the particle size distribution of mixed liquor and DM has a decreasing trend at higher SRT. The average particle size of DM was larger than that of the mixed liquor irrespective of SRT. The amounts and types of microorganisms on the surface of DM were more abundant as SRT increased. Low SRT produced the DM surface with some Cocci while the high SRT gave the DM dominated with Cocci, Filamentous and Bacillus. PMID- 21977656 TI - Tracing fine sediment sources in small mountain catchment. AB - Fine sediment represents an important diffuse source pollutant in surface waters, due to its role in governing the transfer and fate of many substances, including nutrients, heavy metals, pesticides and other organic contaminants, and its influence on aquatic ecology. Therefore, catchment management strategies frequently need to include provision for the control of sediment mobilization and delivery. The sediment tracing concept provides a valuable framework for assisting the management and control of diffuse source sediment pollution by identifying the key sources and demonstrating the importance of intermediate storages and the likely impact of upstream mitigation strategies on downstream sediment and sediment associated contaminant fluxes. In this research, fine sediment sources were identified using tracing method. By field works, sediments were sampled from dam reservoir, different sources were also sampled. Fifteen tracers were first selected for tracing which are: The amounts of N, P, C, Cr, Co, Mg, K, Na, smectite, chlorite, illite, kaolinite, and two magnetic properties consisting of LOW Frequency Magnetic Susceptibility (X(LF)) and Frequency Dependent Magnetic Susceptibility (X(FD)). The samples were analyzed in the laboratory for these parameters and different statistical methods were applied to the data including Non-parametric Kruskal-Wallis Test and Stepwise Discriminant function analysis. The results provide important information on the relative importance of fine sediment sources to the reservoir sediments, which can be used to support model validation and the targeting of management and control strategies. PMID- 21977657 TI - Discussion of the enabling environments for decentralised water systems. AB - Decentralised water supply systems are becoming increasingly affordable and commonplace in Australia and have the potential to alleviate urban water shortages and reduce pollution into natural receiving marine and freshwater streams. Learning processes are necessary to support the efficient implementation of decentralised systems. These processes reveal the complex socio-technical and institutional factors to be considered when developing an enabling environment supporting decentralised water and wastewater servicing solutions. Critical to the technological transition towards established decentralised systems is the ability to create strategic and adaptive capacity to promote learning and dialogue. Learning processes require institutional mechanisms to ensure the lessons are incorporated into the formulation of policy and regulation, through constructive involvement of key government institutions. Engagement of stakeholders is essential to the enabling environment. Collaborative learning environments using systems analysis with communities (social learning) and adaptive management techniques are useful in refining and applying scientists' and managers' knowledge (knowledge management). PMID- 21977658 TI - Aerobic biological treatment of thermophilically digested sludge. AB - Aerobic biological treatment of digested sludge was studied in a continuously operated laboratory set-up. An aerated reactor was filled with thermophilically digested sludge from the Moscow wastewater treatment plant and inoculated with special activated sludge. It was then operated at the chemostat mode at different flow rates. Processes of nitrification and denitrification, as well as dephosphatation, occurred simultaneously during biological aerobic treatment of thermophilically digested sludge. Under optimal conditions, organic matter degradation was 9.6%, the concentrations of ammonium nitrogen and phosphate decreased by 89 and 83%, respectively, while COD decreased by 12%. Dewaterability of digested sludge improved significantly. The processes were found to depend on hydraulic retention time, oxygen regime, and temperature. The optimal conditions were as follows: hydraulic retention time 3-4 days, temperature 30-35 degrees C, dissolved oxygen levels 0.2-0.5 mg/L at continuous aeration or 0.7-1 mg/L at intermittent aeration. Based on these findings, we propose a new combined technology of wastewater sludge treatment. The technology combines two stages: anaerobic digestion followed by aerobic biological treatment of digested sludge. The proposed technology makes it possible to degrade the sludge with conversion of approximately 45% volatile suspended solids to biogas, to improve nitrogen and phosphorus removal in reject water from sludge treatment units, and to achieve removal of malodorous substances after 8-9 days of anaerobic-aerobic sludge treatment. PMID- 21977659 TI - Addition of a magnetite layer onto a polysulfone water treatment membrane to enhance virus removal. AB - The applicability of low-pressure membranes systems in distributed (point of use) water treatment is hindered by, among other things, their inability to remove potentially harmful viruses and ions via size exclusion. According to the USEPA and the Safe Drinking Water Act, drinking water treatment processes must be designed for 4-log virus removal. Batch experiments using magnetite nanoparticle (nano-Fe3O4) suspensions and water filtration experiments with polysulfone membranes coated with nano-Fe3O4 were conducted to assess the removal of a model virus (bacteriophage MS2). The membranes were coated via a simple filtration protocol. Unmodified membranes were a poor adsorbent for MS2 bacteriophage with less than 0.5-log removal, whereas membranes coated with magnetite nanoparticles exhibited a removal efficiency exceeding 99.99% (4-log). Thus, a cartridge of PSf membranes coated with nano-Fe3O4 particles could be used to remove viruses from water. Such membranes showed negligible iron leaching into the filtrate, thus obviating concern about coloured water. Further research is needed to reduce the loss of water flux caused by coating. PMID- 21977660 TI - Vegetated ditches for treatment of surface water with highly fluctuating water regime. AB - Vegetated drainage ditches (VDD) as a type of constructed wetland primarily serve to remove and store excess water associated with irrigation and storm events. Current research suggests using a VDD as an additional practice in the mitigation of surface water pollution. The VDD for water treatment of the Glinscica River was constructed in 2006. The efficiency of the system was evaluated in 2008 and 2009 regarding the reduction of SS, COD, BOD5, NH4-N, NO3-N, NO2-N, TN, ON and TP. The microbiological association developed in the VDD was analyzed with a focus on the identification and quantification of the narG gene as a denitrification indicator. This paper discusses the efficiency of pollution removal and the distribution of the narG gene within the VDD. The results showed that the highly fluctuating water regime was the main reason for the even distribution and abundance of the narG gene throughout the system, regardless of oxygen saturation or the nutrient status of the wastewater. With the exception of SS, pollutant concentrations met the permitted outflow levels. PMID- 21977661 TI - Effect of recirculation on organic matter removal in a hybrid constructed wetland system. AB - This research project aimed to determine the technologically feasible and applicable wastewater treatment systems which will be constructed to solve environmental problems caused by small communities in Turkey. Pilot-scale treatment of a small community's wastewater was performed over a period of more than 2 years in order to show applicability of these systems. The present study involves removal of organic matter and suspended solids in serially operated horizontal (HFCW) and vertical (VFCW) sub-surface flow constructed wetlands. The pilot-scale wetland was constructed downstream of anaerobic reactors at the campus of TUBITAK-MRC. Anaerobically pretreated wastewater was introduced into this hybrid two-stage sub-surface flow wetland system (TSCW). Wastewater was first introduced into the horizontal sub-surface flow system and then the vertical flow system before being discharged. Recirculation of the effluent was tested in the system. When the recirculation ratio was 100%, average removal efficiencies for TSCW were 91 +/- 4% for COD, 83 +/- 10% for BOD and 96 +/- 3% for suspended solids with average effluent concentrations of 9 +/- 5 mg/L COD, 6 +/- 3 mg/L BOD and 1 mg/L for suspended solids. Comparing non-recirculation and recirculation periods, the lowest effluent concentrations were obtained with a 100% recirculation ratio. The effluent concentrations met the Turkish regulations for discharge limits of COD, BOD and TSS in each case. The study showed that a hybrid constructed wetland system with recirculation is a very effective method of obtaining very low effluent organic matter and suspended solids concentrations downstream of anaerobic pretreatment of domestic wastewaters in small communities. PMID- 21977662 TI - A promising approach of reject water treatment using a tidal flow constructed wetland system employing alum sludge as main substrate. AB - This study examined a novel reuse of alum sludge, an inescapable by-product of drinking water treatment process when aluminium salt is added as a coagulant, as the main medium in a laboratory-scale multi-stage constructed wetland (CW) system for reject water treatment. Such reject water is a main concern in municipal wastewater treatment plant (MWWTP) for increasing the organic and nutrient loading. A 'tidal flow' strategy was employed to enhance the wetland aeration to stimulate organic matters (OM) and ammoniacal-nitrogen (N) oxidation while the 'step feed' operation was adopted to supply the necessary amount of carbon source for denitrification. The results reveal that alum sludge acting as P adsorbent can secure the P removal. Meanwhile, high removals of N and OM can also be obtained due to the active bacteria growth on the alum sludge surface. The results show that average removal efficiencies of 65.4 +/- 12.3% for chemical oxygen demand (COD), 67.8 +/- 9.2% for five-day biochemical oxygen demand (BOD5), 33.6 +/- 17.0% for N and 99.5 +/- 0.49% for P can be achieved over a period of 190 days. This indicates that novel reuse of alum sludge as medium in CW system can provide a promising approach for reject water treatment. Therefore, it will significantly reduce the amount of pollutant feedback through reject water recycling in a MWWTP. PMID- 21977663 TI - P distribution in different sediment fraction of a constructed wetland. AB - The aim of this work was to study the accumulation and fractionation of P in the inlet and outlet sediment of a constructed wetland for the wastewater treatment of a metallurgic plant in Argentina. It was important to predict whether P could be released into the water again by changing environmental conditions or retained over time. P-fractionation was performed using a sequential extraction method. Sediment cores were sliced at depths of: 0-3; 3-7 and 7-10 cm. Sediment showed high pH values and anoxic conditions. In the inlet area, P was principally bound to the carbonate fraction, whereas in the outlet area, it was mainly bound in the residual fraction. This behavior was justified by the effluent composition, which is rich in Ca2+ and Fe3+ and presents high values of pH and conductivity. These conditions favor CaCO3 and Fe(OOH)n precipitation and the subsequent sorption of P to their surface. The sediment active layer involved in the exchange reactions was the superficial one (0-3 cm). The wetland is highly efficient in P retention. P was retained by sediment in fractions that will not release it to the water while chemical and environmental conditions of the system are maintained. PMID- 21977664 TI - Catalytic wet air oxidation with Ni- and Fe-doped mixed oxides derived from hydrotalcites. AB - Catalytic wet air oxidation of Basic Yellow 11 (BY11), a basic dye, was studied in a batch reactor. Layered double hydroxides with the hydrotalcite-like structure containing nickel or iron cations have been prepared by coprecipitation and subsequently calcined leading to Ni- and Fe-doped mixed oxides, respectively. Compared with the results in the wet air oxidation of BY11, these catalysts showed high activity for total organic carbon (TOC), toxicity and dye removal at 120 degrees C and 50 bars after 120 min. It has been demonstrated that the activity depended strongly on the presence of catalyst. The results show that catalysts containing nickel provide a higher extent of oxidation of the dye whereas the reaction carried out with the iron catalyst is faster. The Ni and Fe dispersion determined from the TPR results was higher for the catalysts with a lower Ni or Fe content and decreased for higher Ni or Fe contents. On the basis of activity and selectivity, the Ni containing catalyst with the medium (3%) Ni content was found to be the best catalyst. Finally, a relationship between metal content of the catalyst and reaction rate has been established. PMID- 21977665 TI - Simultaneous copper, cobalt and phenol removal from aqueous solutions by alternating biosorption and biodegradation. AB - A strategy for removal of heavy metals and phenol from wastewaters is proposed. It involves consecutive cation biosorption by fungi, phenol biodegradation by the yeast association Candida sp. 2326 + Candida sp. 2327 and regeneration. Copper and cobalt removal from aqueous solutions containing 80-120 mg/L phenol by biosorption, using Rhizopus archizus cells immobilized onto poly (vinyl alcohol), was investigated by conducting a series of batch experiments. The removal efficiencies were 81% for Cu and 5% for Co. The residual concentrations of Cu (1.9 mg/L) and of Co (9.5 mg/L) did not change the biodegradation dynamics of phenol. A quantitative biodegradation of 120 mg/L phenol proceeded within 22 h. After biodegradation of phenol, the removal efficiencies achieved by biosorption after regeneration were 90% for Cu and 44% for Co. It was found that copper and cobalt form positively charged complexes with phenol. This complex formation hinders the retention of Cu and Co by the biosorbent and reduces the uptake of their cations. PMID- 21977666 TI - Improving collected rainwater quality in rural communities. AB - The country of Mexico is facing serious problems with water quality and supply for human use and consumption in rural communities, mainly due to topographic and isolation. In Mexico the average annual precipitation is 1,500 cubic kilometers of water, if 3% of that amount were used, 13 million Mexicans could be supplied with drinking water that they currently do not have access. Considering the limited infrastructure and management in rural communities, which do not receive services from the centralized systems of large cities, a modified pilot multi stage filtration (MMSF) system was designed, developed, and evaluated for treating collected rainwater in three rural communities, Ajuchitlan and Villa Nicolas Zapata (Morelos State) and Xacxamayo (Puebla State). The efficiencies obtained in the treatment system were: colour and turbidity >93%. It is worth mentioning that the water obtained for human use and consumption complies with the Mexican Standard NOM-127-SSA1-1994. PMID- 21977667 TI - Algal production in wastewater treatment high rate algal ponds for potential biofuel use. AB - Wastewater treatment High Rate Algal Ponds with CO2 addition could provide cost effective and efficient tertiary-level wastewater treatment with the co-benefit of algal biomass production for biofuel use. Wastewater grown algal biomass can have a lipid content of 10-30% of dry weight, which could be used to make biodiesel. This research investigated algal biomass and total lipid production by two pilot-scale wastewater treatment HRAP(S) (4-day HRT) with and without CO2 addition under New Zealand mid summer (Nov-Jan) conditions. The influence of CO2 addition on wastewater treatment performance was also determined. CO2 was added to one of the HRAPs (the HRAP(E)) by maintaining the maximum pH of the pond below 8. Measurements of HRAP influent and effluent water qualities, total lipid content and algal biomass production were made twice a week over the experimental period. Both HRAP(S) achieved high levels of organic compound and nutrient removal, with >85% SBOD5, >92 NH4(+)-N and >70% DRP removal. Algal/bacterial biomass production in the HRAP(E) (15.2 g/m2/d) was improved by CO2 addition by approximately 30% compared with that of the control HRAP(W) (10.6 g/m2/d). Total lipid content of the biomass grown on both HRAP(S) was slightly reduced (from 25% to 20%) with CO2 addition and the maximum total lipid content of approximately 40% was observed in the HRAP(W) when low NH4(+)-N concentration (<0.5 mg/L) and high maximum pH (>10.0) occurred. Total lipid content of the biomass increased by approximately 15% under nitrogen limiting conditions, however, overall algal/bacterial biomass production was reduced by half during the period of nitrogen limitation. More research is required to maintain algal production under near nitrogen-limiting conditions. PMID- 21977668 TI - Comparison of PPCPs removal on a parallel-operated MBR and AS system and evaluation of effluent post-treatment on vertical flow reed beds. AB - The presence in the aquatic environment of xenobiotics such as Pharmaceutical and Personal Care Products (PPCPs) has emerged as an issue of concern. Upgrading sewage treatment quality with modern technologies such as Membrane Bioreactors (MBRs) and/or implementing a further posttreatment might mitigate the release of xenobiotics into surface waters. The performance of two processes treating municipal sewage, a MBR and an Activated Sludge (AS) unit, have been compared in terms of PPCPs removal. Moreover, their effluents were treated using vertical flow reed beds. Both systems were operated under similar conditions, more specifically Hydraulic Retention Time (HRT), maintained at 8 hours, and Sludge Retention Time (SRT) set at 6 and 20 days. Pharmaceuticals belong to therapeutic groups such as antiepileptics (carbamazepine) and analgesics (ibuprofen, naproxen, diclofenac), whereas the personal care products are musk fragrances (galaxolide and tonalide). Xenobiotics removals achieved in the MBR showed better results, particularly for the acidic drugs ibuprofen (87% vs. 50%) and naproxen (56% vs. 6%) operating at low SRT. After filtration through vertical flow reed beds, PPCPs content in effluents was decreased, below 1 ppb in most cases, improving the effluent quality and confirming reed-beds as an interesting low cost alternative in order to attenuate xenobiotics contamination. PMID- 21977669 TI - Passive samplers for chemical substance monitoring and associated toxicity assessment in water. AB - The European legislation, and in particular the Water Framework Directive requires the development of cost efficient monitoring tools that can provide the required information for the assessment of water contamination. Passive sampling methods represent one of the novel tools that have a potential to be used in various regulatory monitoring programmes aimed at assessing the levels of chemical pollutants. These methods are particularly interesting for sampling polar organic pollutants in water because they provide representative information of the water quality over extended time periods (days to weeks) in environments with fluctuating contaminant concentrations. This is achieved by integrative sampling of pollutants over the whole sampler deployment period. These tools can be coupled to toxicity testing using bioassays that give information on toxic and ecotoxic hazards associated to substances that are present, these substances being identified or not. In this study the polar organic chemical integrative sampler (POCIS) was used in surface water to evaluate the water contamination by polar organic compounds and their potential toxicity. PMID- 21977670 TI - Identification of humic acid-like and fulvic acid-like natural organic matter in river water using fluorescence spectroscopy. AB - Identifying the extent of humic acid (HA)-like and fulvic acid (FA)-like natural organic matter (NOM) present in natural water is important to assess disinfection by-product formation and fouling potential during drinking water treatment applications. However, the unique fluorescence properties related to HA-like NOM is masked by the fluorescence signals of the more abundant FA-like NOM. For this reason, it is not possible to accurately characterize HA-like and FA-like NOM components in a single water sample using direct fluorescence EEM analysis. A relatively simple approach is described here that demonstrates the feasibility of using a fluorescence excitation-emission matrix (EEM) approach for identifying HA like and FA-like NOM fractions in water when used in combination with a series of pH adjustments and filtration steps. It is demonstrated that the fluorescence EEMS of HA-like and FA-like NOM fractions from the river water sample possessed different spectral properties. Fractionation of HA-like and FA-like NOM prior to fluorescence analysis is therefore proposed as a more reasonable approach. PMID- 21977671 TI - Toxicity assessment of free form of heavy metals in aqueous media on earthworm Eudrillus eugeniae. AB - Metals are found in free and also in combined forms. In order to get information on the effect of free forms of heavy metals on earthworms the aqueous extracts of metals were tested on earthworms both in individual form and also in combined form. Different concentrations, i.e. 1 ppm, 5 ppm, and 10 ppm, were selected arbitrarily and were used in the experiments. Metals like copper, cadmium, chromium, zinc and lead were used. Earthworms' Eudrillus eugeniae activity, i.e. their response to the toxicity of metals, was monitored continuously for 5 h. It can be concluded that free form/ionic form/dissolved form of heavy metals are more toxic for earthworms, concurrent with findings of workers who have drawn same inference during studies on aquatic organisms. Earthworms can serve as biomarkers for wastewater and sludge treatment studies as they have shown typical adverse body reactions and symptoms altogether different in reaction to each of the metals during aqueous medium studies. It can be inferred that, if earthworms are utilised for treating wastewater and sludges containing these five heavy metals, one can ascertain the presence of individual metal concentrations in the wastewaters and sludges by studying the typical body reactions of earthworms during the treatment. PMID- 21977672 TI - Calibration and verification of models of organic carbon removal kinetics in Aerated Submerged Fixed-Bed Biofilm Reactors (ASFBBR): a case study of wastewater from an oil-refinery. AB - The article presents a case-study on the calibration and verification of mathematical models of organic carbon removal kinetics in biofilm. The chosen Harremoes and Wanner & Reichert models were calibrated with a set of model parameters obtained both during dedicated studies conducted at pilot- and lab scales for petrochemical wastewater conditions and from the literature. Next, the models were successfully verified through studies carried out utilizing a pilot ASFBBR type bioreactor installed in an oil-refinery wastewater treatment plant. During verification the pilot biofilm reactor worked under varying surface organic loading rates (SOL), dissolved oxygen concentrations and temperatures. The verification proved that the models can be applied in practice to petrochemical wastewater treatment engineering for e.g. biofilm bioreactor dimensioning. PMID- 21977673 TI - Anode and cathode materials characterization for a microbial fuel cell in half cell configuration. AB - Microbial fuel cells (MFCs) are novel bioelectrochemical devices for spontaneous conversion of biomass into electricity through the metabolic activity of the bacteria. Microbial production of electricity may become an important source of bioenergy in future because MFCs offer the possibility of extracting electric current from a wide range of soluble or dissolved complex organic wastes and renewable biomass. However, the materials used in these devices are still not economic and researchers use different materials as cathode and anode in MFCs. This results in variable performance which is difficult to compare. We tested several commercially available materials for their suitability as anode in an acetate fed MFC. Besides, a novel non-platinized activated carbon (AC) based, gas porous air cathode was also tested. Both the anode and cathode were tested in a half cell configuration. Carbon cloth, graphite cloth and dynamically stable anode (DSA) served as ideal anode material with carbon cloth and graphite mesh reaching the open circuit voltage (OCV) of acetate oxidation (-500 mV vs. Ag/AgCl). The effect of increasing concentration of acetate on anode OCV was also investigated and results showed that on increasing the acetate concentration from 10 mM to 40 mM has no adverse impact on the anodic activity towards electrochemical oxidation of acetate. The AC cathode showed stable current (-1.2 mA/cm2) over a period of 100 days. PMID- 21977674 TI - Experiences on dual media filtration of WWTP effluent. AB - This research is legislation driven by the European Water Framework Directive (WFD) and the Dutch Fourth Memorandum on Water Management. The objective of this research is to achieve the removal of total nitrogen and total phosphorus by Dual Media Filtration. The target value during this research for total nitrogen is 2.2 mg/L and for total phosphorus 0.15 mg/L. The results show that for NOx-N concentrations in the WWTP effluent up to 10 mg/L, a stable operation of the process can be reached with removal rates of 80% to 90%. The maximum nitrogen removal rate was 3.5 kg N/(m3.d). Above 10 mg/L a risk of filter bed clogging occurred. When the orthophosphorus concentration in the WWTP effluent exceeds the maximum of 0.3 mg/L, the total phosphorus concentration in the filtrate water will exceed the target value of 0.15 mg P-total/L. Temperature has a large impact in the phosphorus removal; the optimum temperature range is within 13 degrees C 18 degrees C. In conclusion, Dual Media Filtration is capable of producing reusable water with total phosphorus concentrations of <0.15 mg/L, under the condition that the wastewater treatment plant produces WWTP effluent with steady concentrations for orthophosphorus (<0.3 mg PO4-P/L). To reach total nitrogen concentrations in the filtrate water of <2.2 mg/L a NOx-N removal efficiency of nearly 100% is required. PMID- 21977675 TI - Worry in older community-residing adults. AB - With rising longevity, increasing numbers of older people are experiencing changes in their everyday family and social life, changes in their financial status, and a greater number of chronic conditions affecting their health. We took the opportunity to explore these relationships with worry in a group of volunteer community-living elderly (n = 310). Findings showed that that those people under 75 years of age had a higher risk of worrying (OR = 1.8, 95% CI = 1.0-3.1) compared to the older age groups. Women worried more than men and an important finding was that those with chronic health conditions such as arthritis of the hip and knee were more prone to worry than those who were healthy or had acute conditions (OR = 3.5, 95% CI = 1.4-8.9). This latter finding suggests the importance placed on the role of the hip and knee in maintaining functional capacity to perform life skills. PMID- 21977676 TI - Applying the Team Identification-Social Psychological Health Model to older sport fans. AB - According to the Team Identification-Social Psychological Health Model (Wann, 2006b), team identification and social psychological health should be positively correlated because identification leads to important social connections which, in turn, facilitate well-being. Although past research substantiates the hypothesized positive relationship between team identification and well-being, earlier studies focused solely on college student populations. The current study extended past work in this area by investigating the team identification/well being relationship among older sport fans. A sample of older adults (N = 96; M age = 70.82) completed scales assessing demographics, identification with a local college basketball team, and measures of social psychological well-being. As hypothesized, team identification accounted for a significant proportion of unique variance in two measures of social psychological health (collective self esteem and loneliness). PMID- 21977677 TI - The relationship between age, gender, historical change, and adults' perceptions of mental health and mental health services. AB - The purpose of this study was to explore the impact of age, historical change, and gender on perceptions of mental health and mental health services. Using multidimensional measures to assess such perceptions among older adults (1977, 1991, 2000), and younger adults (1991, 2000), we expected that older adults would have less positive mental health perceptions than would younger adults, that more recently born cohorts of older persons would evidence more positive perceptions, and that women, especially those more recently assessed, would also evidence more positive perceptions. To an extent, we found positive historical shifts in mental health perceptions, though data also indicated that such views may have stabilized over the last decade for older persons, and interacted with age and gender in this respect. Age differences favoring younger persons were, in part, replicated across historical time, and women held more positive mental health perceptions than did men. Over historical time, older persons' mental health perceptions are, for the most part, increasingly positive, significant in light of the increasing proportion of older persons and changes in the mental health system itself. Our data suggest that efforts to reach older men should be given high priority. PMID- 21977678 TI - Perceived strategies and activities for successful later aging. AB - This study investigated perceived strategies and activities for successful later aging. Participants were 242 members of the Terman Study of the Gifted who responded to an open-ended question concerning how they make the most of their aging years. Data were collected in 1996 and 1999, when the participants were average ages of 84 and 86. Longitudinal analyses examined changes over time and cross-sectional analyses examined correlates of strategies and activities. Results showed that strategies emphasized emotion regulation and adaptation. Activities emphasized family involvement, social relationships, leisure, productive and intellectual activity, and health maintenance. Reports of emotion regulation and adaptation increased over time and mention of an intellectual orientation declined over time. Variations in activity mention were found according to gender, age, self-rated health, health limitations, and life satisfaction. History of higher-level occupations was related to more productive activities. Results are discussed in terms of the challenges of later aging. PMID- 21977679 TI - Driving home the need for safety. PMID- 21977680 TI - Reference group set up for nurses who treat children. PMID- 21977681 TI - Up in flames: the personal cost of the riots in Croydon. PMID- 21977682 TI - Silent order: encouraging respect for bereaved families. PMID- 21977683 TI - Use of GPs. PMID- 21977684 TI - Driving after discharge: advising injured patients. AB - This article seeks to clarify the legal position on driving by people who have been discharged from emergency departments or minor injury units after treatment for injuries. It discusses a literature review about the advice such people are given and the advice they want, and the responsibility of clinicians in providing this. It also provides examples of written advice on driving after discharge. PMID- 21977685 TI - Venous thromboembolism: reducing the risk. AB - This article demonstrates how services provided in minor injury units (MIUs) and emergency departments (EDs) can be improved by the implementation of routine thromboprophylaxis by subcutaneous injections of low molecular weight heparin for patients whose lower limbs are immobilised by plaster casts. The author offers evidence of the need for such a change in practice from a literature review and a case study, and describes how it can be achieved in five steps. She also outlines a protocol for routine thromboprophylaxis in MIUs and EDs. PMID- 21977686 TI - Use of digital nerve blocks to provide anaesthetic relief. AB - This article discusses the various techniques that nurses can use to perform digital nerve blocks, which are some of the most common procedures undertaken by emergency practitioners treating patients with finger injuries. In covering the advantages and disadvantages of each technique, it focuses primarily on the digits of the hand, but the techniques can also be performed on toes. PMID- 21977687 TI - Nurse burnout and the working environment. AB - AIM: This article examines levels of burnout experienced by emergency nurses and the characteristics of their work environment to determine if there is a relationship between the two. METHOD: A literature review of recent articles on emergency nurses' burnout and contributing factors was undertaken. A quantitative study, in which nurses were asked to indicate the extent of their agreement with a series of statements on burnout and the working environment, was then undertaken, and the results were analysed to ascertain the extent to which the two topic are related. FINDING: The results indicate that 52 per cent of nurses in an emergency department in Ireland experience high levels of emotional exhaustion and depersonalisation, which are significantly related to the nature of their work environment. CONCLUSION: Improvements to the environment and to education are required to reduce the risk of nurses developing burnout in the future. PMID- 21977689 TI - Birth order effects on the separation process in young adults: an evolutionary and dynamic approach. AB - The present study analyzes the differential contribution of a familial or social focus in imaginative ideation (the personal fable and imagined audience mental constructs) to the separation-individuation process of firstborn, middleborn, and lastborn children. A total of 160 young adults were divided into 3 groups by birth order. Participants' separation-individuation process was evaluated by the Psychological Separation Inventory, and results were cross-validated by the Pathology of Separation-Individuation Inventory. The Imaginative Ideation Inventory tested the relative dominance of the familial and social environments in participants' mental constructs. The findings showed that middleborn children had attained more advanced separation and were lower in family-focused ideation and higher in nonfamilial social ideation. However, the familial and not the social ideation explained the variance in the separation process in all the groups. The findings offer new insights into the effects of birth order on separation and individuation in adolescents and young adults. PMID- 21977688 TI - Age of acquisition in sport: starting early matters. AB - Although the age at which a skill is learned (age of acquisition [AoA]) is one of the most studied predictors of success in domains ranging from language to music, very little work has focused on this factor in sports. In order to uncover how the age at which a skill is learned relates to how athletes cognitively represent that skill, we asked a group of skilled golfers who learned to play golf before (early learners) or after (late learners) the age of 10 to take a series of putts on an indoor putting green. Golfers putted in isolation (single-task condition), while monitoring a stream of words presented over a loudspeaker (dual-task condition), or while being instructed to attend to specific aspects of their golf swing (skill-focused condition). Early and late learners putted equally well in the single-task and dual-task conditions. However, in the skill-focused condition, golfers who learned earlier performed worse than those who learned later. The results are consistent with the notion that AoA influences the manner in which sports, like other domains such as language and music, are represented in memory. PMID- 21977690 TI - Working memory contributions to reading comprehension components in middle childhood children. AB - This study examined working memory contributions to reading comprehension subskills in Greek children (mean age 9 years, 1 month). The phonological loop of the Baddeley and Hitch working memory model was assessed with 3 recall tasks (words, nonwords, and digits) and a word list matching task. The central executive (CE) was assessed with 3 tasks (listening, counting, and backward digit recall). Participants were also given a receptive vocabulary task, a reading fluency task, and written stories accompanied by comprehension questions. Canonical correlation analyses showed that the comprehension variables were related to the CE rather than the phonological loop measures. CE functions were more strongly associated with elaborative inference generation (involving significant offline processing) and comprehension control (involving metacognitive monitoring). Smaller yet significant associations were observed between the CE and the necessary inference and literal comprehension measures, whereas a moderate relationship was found in the case of the simile comprehension variable. Among the CE variables, listening recall demonstrated the highest loading on the canonical function, followed by moderate yet significant counting and backward digit recall loadings. Vocabulary was found to fully mediate several associations between working memory and comprehension measures; however, the relationship between listening recall and elaborative inferences was partly mediated. Reading fluency and, on several occasions, Greek vocabulary knowledge did not mediate the relationships between CE measures and comprehension skills assessed. This study demonstrates the usefulness of CE measures for identifying young children's possible difficulties in carrying out specific reading comprehension processes. PMID- 21977691 TI - Influence of cognitive abilities and age on word recall performance across trials and list segments. AB - The influence of cognitive abilities and age on multitrial word recall performance was examined for different list segments (i.e., first, middle, and last) and across trials by having 2497 participants ages 18-98 complete a multitrial word list test along with reference cognitive ability tests. As expected, higher episodic memory ability was associated with better recall on all list segments but with a smaller influence for the last items on the early trials. Performance improved across trials, but there were no relations of the fluid intelligence construct that might be postulated to be associated with effective strategy implementation with any of the recall measures. Advanced age was associated with lower levels of performance, but very few of the age relations were significant after the variation in the reference cognitive abilities was controlled for. PMID- 21977693 TI - The odd-even effect in Sudoku puzzles: effects of working memory, aging, and experience. AB - The odd-even effect in numerical processing has been explained as the easier processing of even numbers compared with odd numbers. We investigated this effect in Sudoku puzzles, a reasoning problem that uses numbers but does not require arithmetic operations. Specifically, we asked whether the odd-even effect occurred with Sudoku puzzles and whether individual differences in working memory (WM), aging, and experience with Sudoku modulated this effect. We manipulated the presence of odd and even numbers in Sudoku puzzles, measured WM with the Wisconsin Card Sorting Test and backward digit span task, tested older and younger adults, and collected Sudoku experience frequency. Performance on Sudoku was more accurate for even puzzles than odd ones. Younger, experienced, and higher-WM participants were more accurate on Sudoku, but these individual difference variables did not interact with the odd-even effect. Odd numbers may impose more cognitive load than even numbers, but future research is needed to examine how age, experience, or WM may influence the odd-even effect. PMID- 21977692 TI - Effects of emotional arousal on memory binding in normal aging and Alzheimer's disease. AB - Previous research suggests that associative memory declines in normal aging and is severely affected by Alzheimer's disease (AD); however, it is unclear whether and how this deficit can be minimized. The present study investigated whether emotional arousal improves associative memory in healthy younger and older adults and patients with probable AD. We examined the effect of arousal on memory for item-location associations. Arousal improved memory for item location similarly across the three groups, whereas valence had no effect in any groups. Overall, our results suggest that arousal has beneficial effects on associative memory in healthy older adults and patients with AD, as previously observed in younger adults. PMID- 21977694 TI - Spatial congruency between stimulus presentation and response key arrangements in arithmetic fact retrieval. AB - It is known that number and space representations are connected to one another in numerical and arithmetic abilities. Numbers are represented using the metaphor of a mental number line, oriented along horizontal and vertical space. This number line also seems to be linked to mental arithmetic, which is based partly on arithmetic fact retrieval. It seems that number representation and mental arithmetic are linked together. The present study tested the effect of spatial contextual congruency between stimulus presentation and response key arrangements in arithmetic fact retrieval, using number-matching and addition verification tasks. For both tasks in Experiment 1, a contextual congruency effect was present horizontally (i.e., horizontal presentation of stimuli and horizontal response key alignments) but not vertically (i.e., vertical presentation of stimuli but horizontal response key alignments). In Experiment 2, both tasks showed a contextual congruency effect for both spatial conditions. Experiment 1 showed that the interference and distance effects were found in the horizontal condition, probably because of the spatial congruency between stimulus presentation and response key arrangements. This spatial congruency could be related to the activation of the horizontal number line. Experiment 2 showed similar interference and distance effects for both spatial conditions, suggesting that the congruency between stimulus presentation and response alignment could facilitate the retrieval of arithmetic facts. This facilitation could be related to the activation of both horizontal and vertical number lines. The results are discussed in light of the possible role of a mental number line in arithmetic fact retrieval. PMID- 21977695 TI - Integration of facial and newly learned visual cues in speech perception. AB - We are developing technology to translate acoustic characteristics of speech into visual cues that can be used to supplement speechreading when hearing is limited. Research and theory have established that perceivers are influenced by multiple sources of sensory and contextual information in spoken language processing. Previous research has also shown that additional sources of information can be learned and used to supplement those that are normally available but have been degraded by sensory impairment or difficult environments. We tested whether people can combine or integrate information from the face and information from newly learned cues in an optimal manner. Subjects first learned the visual cues and then were tested under three conditions.Words were presented with just the face, just the visual cues, or both together. Performance was much better with both cues than with either one alone. Similar to the description of previous results with audible and visible speech, the present results were well described by the Fuzzy Logical Model of Perception (Massaro, 1998), which predicts optimal or maximally efficient integration. PMID- 21977696 TI - The Southern Society for Philosophy and Psychology and Francis Cecil Sumner. AB - In 1939, a psychologist could become a member of the Southern Society for Philosophy and Psychology (SSPP) automatically with the endorsement of two members, payment of dues, and membership in the American Psychological Association (APA). Non-APA members with endorsements and payment of dues had to be voted in by the membership. In 1940, the rules for admission were changed to eliminate the automatic membership for APA members. Francis Cecil Sumner, the first African American PhD in psychology, qualified for SSPP membership as a member of the APA in 1939, but the SSPP's council delayed his membership and introduced the amendment to its constitution that eliminated Sumner's route to membership. This article examines the circumstances surrounding council's actions and the role that Sumner's application for membership played in it as an example of the role that race and discrimination played in the decision to change the route to SSPP membership for members of the APA. PMID- 21977697 TI - The "Deglutition Handicap Index" a self-adminitrated dysphagia-specific quality of life questionnaire: sensibility to change. AB - OBJECTIVE: The aim of this study is to assess the efficacy of UES's dysfunction treatments with the DHI (Deglutition Handicap Index). MATERIAL AND METHOD: 24 patients suffering of UES's dysfunction were included prospectively between 2008 and 2009 in 2 centers (France and Netherlands). Patients completed DHI before and after treatment. For statistics, Wilcoxon two-sample tests were used. RESULTS: The mean score was 57 +/- 17 in the preoperative and 26 +/- 19 in the post operative time. The statistical difference was significant p < 0.0001. The difference is also significant for the 3 subscales (symptoms, functional, emotional). CONCLUSION: The DHI has been validated in terms of content, concurrent, construct validity and temporal reliability. It can be used for assessing efficacy of treatments used for dysphagia. PMID- 21977698 TI - [Context influence on the perception of dysphonia: when the knowledge of the patient's clinical state can modify the results of perceptual voice quality assessment]. AB - Two experiments were conducted to examine how knowledge of the patient's clinical state affects the results of perceptual voice quality assessment performed by specialists in voice therapy. This study involved 53 patients with a dysphonia. For each speaker, we selected a pair of recordings made in different circumstances. These pairs of voices were presented to seven listeners (ENT surgeons or speech therapists). The task was to perceptually compare the severity of the dysphonia between the 2 recordings of the pair. Stimuli were presented first in a blind test, then several weeks later with accompanying information about the patient; in particular, whether the voice was pre- or post- treatment was explicitly specified. We balanced this artificial contextual information in order to (alpha) reinforce the blind judgment (for example, voices perceived as better in the blind test were indicated as post treatment); (beta) be inconsistent (in a clinical point of view) compared to the blind test (for example, voices perceived as more disordered during the blind test were indicated as post treatment). Results revealed that in the clinical-consistent context alpha, the preference was amplified in a significant way. In clinical inconsistent condition beta, we observed an inhibition effect or a change of decision. In this condition, the judgment was more dependant on the contextual information (pre/post treatment) than on the auditory sensation obtained in blind condition. These findings are discussed with reference to results in the literature on visual, olfactory or auditory perception in context. In the frame of perceptual voice assessment, results revealed that only blind tests can provide reliable results. PMID- 21977699 TI - [Perceptual assessment of dysphonia: a training protocol with natural speech]. AB - INTRODUCTION: In this study, we proposed and tested the effectiveness of a training procedure on perceptual evaluation of dysphonia. Participants were naive listeners who learned to judge the severity of vocal disorders. MATERIALS AND METHODS: The corpus consisted of 142 female voices ranging from normal to severely dysphonic voices. A total of 38 naive listeners were tested, and the experiment was divided in 3 phases: (1) A pretest to assess the level of our listeners in the categorization of dysphonia, (2) the training phase and (3) a post-test to assess the improvement associated with the training. To examine the persistence of the training, the post-test was administrated twice: Immediately after the training session and one week later. RESULTS: Improvement in the performance between the pretest and the post-test was found for moderate and severe dysphonia. No improvement was observed in the categorization of slightly dysphonic voices, which seem the more resistant to learning. Normal voices also showed no improvement, which is likely due to the high performance on these voices during the pre-test. The improvement observed in the categorization of moderate and severe dysphonia was still present even one week after the training. DISCUSSION: The protocol tested in this study appears to be effective and could constitute an element of training courses for speech and voice therapists. The perception of the intermediate levels of dysphonia, however, remains difficult to quantify and needs to be improved. PMID- 21977700 TI - [Proposal of a rating scale of posture for simple dysfunctional dysphonia: "S TRAV"]. AB - OBJECTIVE: This work aims to create a scale to evaluate posture, quick and easy to perform during the assessment of voice in patients with simple dysfunctional dysphonia. MATERIAL AND METHOD: The "S-TRAV" scale was evaluated on 60 subjects with dysphonia and 60 control subjects. It assesses "the overall severity" of the alteration of posture, the "Tension", the "Breathing", the "Ground anchoring" and the "Verticality" both quantitatively (score 0-3) and qualitatively. The patient also assesses his voice disorder and his posture. Postural observation was carried out in five conditions: at rest, conversational voice, reading, projected voice and singing voice. The comparison between the dysphonic subjects and control subjects was used to assess the sensitivity of this tool. Two reviewers rated the scale to determine its reproducibility. RESULTS: The scale is sensible for the majority of criteria with a significance coefficient less than 0.05. The most discriminate criteria relate to the cervical spine, the overall score of postural severity assessed by the therapist and verticality. All criteria have a low level of variability between the reviewers under all conditions. Most criteria are correlated with the criterion "Overall Severity" of postural alterations under all conditions. Non-sensible criteria were eliminated from the final scale). CONCLUSION: This tool is sensitive, reproducible and relevant in assessing the severity of postural alterations and their location. Further studies will validate the scale on a consistent population. PMID- 21977701 TI - [The prevention of voice disorders in the actor: protocol and follow-up nine months of professional theater]. AB - In July 2009, at the beginning of this work, 26 theses addressing professional principles of voice were listed in the database of SUDOC (Systeme Universitaire de Documentation): 9 related to voices of teachers (about 900,000* professionals in France), 14 theses relating to singers (7500** professionals), and only 3 about the voice of actors (20 000*** professional actors in France in 2006). The latter pertaining to concerning rookie actors (sensibilisation vocale aupres du comedien debutant Bichet, Linda, Bordeaux II, 2006), the mechanical larynx (etude des mecanismes larynges dans la voix projetee: cas particulier des comediennes Guerin, Melanie, Paris VI, 2009), vocal fatigue (Fatigue vocale apres une tache d'utilisation prolongee de la voix chez le comedien Canaan Baggioni, Brigitte, Aix-Marseille II, 2009). Professional actors are plentiful; their training in vocal technique is very heterogeneous, or non-existent: it is not a prerequisite to have a degree to work as an actor! This lack of vocal technique is associated with risk factors specific to the acting profession: numerous travels in air conditioned vehicles, unsuitable workplaces; dusty or poorly heated, irregular working patterns, excessive demands from directors... All this makes the actors highly susceptible to voice disorders. The protocol for the prevention of voice disorders presented here is holistic and ecological. This work also examines the effectiveness of such a preventive protocol aimed at theatre comedians. PMID- 21977702 TI - [Unilateral laryngeal paralysis after intra capsular loboisthmectomy without laryngeal nerve dissection]. AB - OBJECTIVES: To document the incidence, outcome and variables that increase the risk for unilateral laryngeal paralysis after loboisthmectomy performed according to the intracapsular dissection technique. MATERIALS AND METHODS: A retrospective analysis of an inception cohort of 317 loboisthmectomies consecutively performed at a single institution by the same surgeon during the years 2002-2007 using the intra capsular dissection without laryngeal nerve dissection, neuromonitoring and modern hemostasis techniques (Ligasure, Ultracision). The immediate and definite rate for unilateral laryngeal nerve paralysis is documented. A statistical analysis is performed for potential relation between these events and the following variables: age, gender, comorbidity, tracheal compression and intrathoracic characteristics of the thyroid lesion, side of the loboisthmectomy, etiology of the thyroid lesion (benign, malignant, hyperthyroidy), associated thyroiditis, size of the largest resected nodule and weight of the resected lobe. RESULTS: The immediate unilateral laryngeal nerve paralysis incidence was 1,2%. Recovery of motion occurred by the 1st, 3rd, 5th or 9th post operative month resulting in a 0% incidence for definitive unilateral laryngeal nerve paralysis. No significant statistical relation was noted between immediate unilateral laryngeal nerve paralysis and the variables under analysis. CONCLUSION: Based on the current series and the review of the medical literature, it appears that the loboisthmectomy according to the intra capsular technique without inferior laryngeal nerve identification, in patients not previously operated, performed according to is a surgical technique whose goal is to ascent the thyroid lobe and dissect the region of the nerve penetration within the larynx by the end of the resection, does not increase the risk for transient or permanent unilateral laryngeal nerve paralysis. PMID- 21977703 TI - [Reverse phonation: pathological and therapeutic aspects. Study of a clinical case]. AB - If the phenomenon of reverse voice is well known as a transitional phenomenon occurring during normal phonation, it is less known as a pathological entity. In this connection it seemed interesting to get a fix on this type of phonation. We will illustrate our discussion with one of our patients for which the reverse voice was continuously used instead of the usual blown voice. We will present all clinical and functional investigations conducted with this patient. We also focused on the particular psycho-dysfunctional context this patient was struggling with. Instrumental investigations concerning the fundamental frequency and the laryngeal aspect allowed us to find the same results as the literature ones. We will then talk about speech therapy, its difficulties and the means proposed to patient in order for him to accept his blown exhalation voice. PMID- 21977704 TI - [Sacrifice was an art: the voice of the castrato]. AB - Introduced in Europe through the mozarabic civilization during the IXth century, the castrato will reign on Baroc Opera theaters in Europe in the XVllth and XVlllth century and will progressively disappear in the XIXth century. Castration is responsible pour morphologic changes not only of the larynx, but also of the skeleton and visceral tissues. These anatomic particularities mixed with a stupefying vocal technic, will create one of the most extraordinary vocal phenomenon of the history of singing, but the price to pay was so high. PMID- 21977705 TI - When some clinical cases can challenge the phoniatric taxonomy. AB - It is proposed that taxonomy--the science and practice of classification--can offer significant help in the assessment of vocal dysfunction and in expanding the range of treatment options available to physicians. The first two clinical cases involve instances of "spasmodic dysphonia" which are susceptible to the usual botulinum toxin injections; those two cases were improved by an equally effective phoniatric orientation that does not subject the patient to repeated injections. Treatment in the second two cases was also redesigned using a phoniatric approach to the patients' problem, after earlier ENT consultations had failed to diagnose malignancy. PMID- 21977706 TI - Strategic clinical manpower planning in the defence medical services beyond Op HERRICK. PMID- 21977707 TI - Do no harm--the limitations of civilian medical outreach and MEDCAP programmes based in Afghanistan. PMID- 21977708 TI - A three-year review of emergency department admissions--Op HERRICK 4 to 9. AB - OBJECTIVES: This paper describes the key themes in presentations to the Emergency Department (ED) of the UK Field Hospital throughout the three-year period of April 2006 to April 2009 (Op HERRICK 4-9). METHODS: Electronic ED attendance records held in the Operational Emergency Department Attendance Register (OpEDAR) were analysed with validation by Defence Analytical Services Agency and commentary by ADMEM clinical staff. RESULTS: This paper discusses absolute numbers of emergency department attendances ofwhich there were 11,158 recorded over the studyperiod. It does not compare them to personnel at risk or operational tempo. Ofthese attendances, 59.7% (n=6666) were U.K. military. Explosive injuries (15.2%, n=1699), particularly Improvised Explosive Devices, increased throughout the period as did gunshotwounds (7.3%, n=809). Battle injuries represented 23.3% (n=2,602) attendances and had a fatality rate of 10.9%. 38.8% (n=4327) of attendances were non-battle injuries and had a fatality rate of 0.4%. There were no fatalities in the 34.1% (n=3,800) attendances for disease. 315 fatalities were recorded (this figure relates to all attendances - not just UK personnel) with 90.2% (n=284) due to battle injuries. 59.4% (n=187) were due to explosives and 28.9% (n=91) due to gunshot wounds. CONCLUSIONS: Over the period, the hospital's workload was characterised by an increase in explosive and gunshot injuries. In this role, the hospital met its obligation of responding to traumatic battle injury in support of fighting power and morale. Equally, the hospital faced a high proportion of attendances for non-battle injury and illness, and by patients from the local population. Extrapolation of data enables accurate medical planning and pre-deployment training and facilitates preparation for current operations. PMID- 21977709 TI - A kinematic and kinetic analysis of drop landings in military boots. AB - OBJECTIVE: The purpose of this study was to examine knee valgus in drop landings during three different footwear conditions and to examine the ground reaction forces exhibited during the drop landing in the three different footwear conditions. METHODS: Sixteen male and female Reserve Officer Training Corps (ROTC) university undergraduate cadets (21 +/- 3 yrs, 79 +/- 12 kg, and 172 +/- 10 cm) volunteered to participate in the study. Kinematic data were collected while participants performed drop landings in three conditions: bare feet, tennis shoes, and issued military boots. RESULTS: Significant differences among footwear for ground reaction forces (bare feet: 1646 +/- 359%, tennis shoe: 1880 +/- 379%, boot: 1833 +/- 438%; p < 0.05) were found, while there was no significant difference in knee valgus among footwear. CONCLUSIONS: Though footwear conditions did not affect knee valgus, they did affect ground reaction forces. Participants in this study had yet to receive any military training on how to land properly from a specified height. Further research should be completed to analyze the kinematics and kinetics of the lower extremity during different landing strategies implemented by trained military personnel in order to better understand injury mechanisms of drop landings in this population. It is likely that injury prevention landing techniques would be beneficial if these were employed by the military and not just in the sporting community. PMID- 21977710 TI - The immediate treatment of frostbite in the American and German armies in Europe during World War 2: an historical perspective. AB - This historical account, based on a survey of 250 medical articles written during and immediately after World War II, reviews the immediate treatment of frostbite in the American and German ground troops in Europe from 1941 to 1945. The American management was simpler and more conservative than the elaborate treatments reported in the German publications. Because the German patients' injuries were more severe than those of the American soldiers and because neither Army carried out strict clinical trials nor prolonged follow-ups, it is impossible to judge what treatment was superior. PMID- 21977711 TI - Fleas on operations in Afghanistan--environmental health measures on the front line. AB - Flea bites can cause irritating symptoms, secondary infections, and may potentiate the spread of vector-borne disease. Flea infestation and bites may also cause significant psychological distress, and can reduce the morale and fighting fitness of deployed military personnel. The problem of flea infestation was highlighted during Op HERRICK 12 in two 'front line' Check Points (CPs) where the entire population of soldiers suffered from multiple symptoms due to flea infestation and bites. Several attempts at infestation control initially succeeded but later lead to recurrence. Such failure was due to the incomplete killing of all stages of the flea life cycle, and due to constraints on education, training, communication, and resupply in the isolated and austere environment of the CPs. A dedicated operation (designated Op Insecticide) was put into action in order to eradicate the problem and return the affected troops back to full fighting fitness. Op Insecticide was thorough, systematic and sustainable, and lead to an eradication of the flea infestation problem at the affected CPs. PMID- 21977712 TI - The use of exercise and dietary supplements among British soldiers in Afghanistan. AB - BACKGROUND AND OBJECTIVES: Recently published case reports, coupled with a large observational study of 1017 deployed servicemen to Iraq (January 2009), has highlighted the issue and potential concerns regarding the unregulated use of dietary and exercise supplements within the British military. Consequently, an exploratory pilot study was undertaken to assess whether the findings of the previous Iraq study were applicable to current deployed British servicemen in Afghanistan. METHODS: This was a voluntary questionnaire-based study targeted at individuals attending a health promotion fair in Camp Bastion, Afghanistan in June 2010. RESULTS: From 150 questionnaires handed out there were 87 completed questionnaires (58% return). The mean age was 28.0 (SD 7.1; range of 18-50 years) with 89.7% being male. From the total of 87 persons 46.0% were self-declared current smokers with 37.9% admitting to drinking >6 caffeinated drinks per day. Forty nine persons (56.3%) admitted to a history of supplement use with 35 (40.2% compared with 32.0% in 2009 in Iraq) declaring current use. The average duration of supplement use among current users was 3.0 (2.0-9.0) months. The main sources of supplement supply were via local NAAFI purchase (57.1%), internet purchase (40.0%) and via their local chemist (2.9%). The main types of supplement used were proteins/amino acids (85.7%), creatine (34.3%), chromium (31.4%), stimulants (17.1%), hydroxycut (5.7%), and testosterone boosters (1.2%) with no persons admitting to the use of ephedra or anabolic steroids. CONCLUSIONS: A significant proportion of the British servicemen employed on operations in Afghanistan who were sampled, admitted to current dietary and exercise supplement use whilst on deployment. The results of this small study suggest that their use on operations may be increasing. Smoking rates and caffeine consumption, on deployment, remain high in the British military. A larger detailed study with greater representation among soldiers deployed to forward operating bases would be helpful to fully appreciate the scale of supplement use. PMID- 21977713 TI - A retrospective study into the levels of evidence presented at the Combined Services Orthopaedic Society annual meeting. AB - OBJECTIVES: The role of Evidence Based Medicine in clinical care is to provide a framework for the integration of expertise, current evidence and the needs of the individual patient. Research presented at scientific meetings is an important source of such evidence, informing clinical decision making both on military operations and in home nation health care systems. The aim of this study is to review the levels of evidence presented at the Combined Services Orthopaedic Society (CSOS) and two other related scientific meetings. METHODS: Retrospective review of abstracts presented at the annual scientific meetings of the CSOS, Society of Military Orthopaedic Surgeons (SOMOS) and the British Trauma Society (BTS). Basic science studies, animal studies, cadaveric studies, surveys and guest lectures were excluded. Research abstracts were categorised according to the Centre for Evidence-Based Medicine's (CEBM) hierarchy of evidence. Statistical comparison was performed to investigate differences in evidence levels presented at each scientific meeting and between each year of the CSOS meeting. RESULTS: 596 abstracts met the inclusion criteria for this study (179 CSOS, 173 SOMOS, 244 BTS). Level IV evidence accounted for the majority of presented abstracts at each meeting (72.6% CSOS, 69.4% SOMOS, 68.9% BTS). Level I evidence was uncommon at each meeting (6.1% CSOS, 5.2% SOMOS, 2.9% BTS). There was no statistical difference in the evidence levels presented at the three scientific meetings. CONCLUSIONS: The proportion of comparative clinical studies (Levels I-III) presented at military or trauma societies' scientific meetings reflects the difficulty of performing research in emergency surgery. This is further exacerbated in the military environment where operational commitments and delivery of care take priority. However, the future value of comparative clinical research in battlefield healthcare could have an enduring legacy that shapes trauma care for many decades. PMID- 21977714 TI - Selective non-operative management of abdominal injury in the military setting. AB - This article represents a consensus view of those TTWG members present in Birmingham and taking into account the views of the other group members via email discussion. We believe it represents clear guidance for the deployed clinician and recommend the use of selective non-operative management when appropriate. PMID- 21977715 TI - Penetrating paediatric thoracic injury. AB - Paediatric penetrating chest trauma is common in conflict, but rarely seen in peacetime. We describe the successful hospital management of a five year old female civilian casualty with life threatening penetrating thoracic trauma caused by a fragment from an explosive device. PMID- 21977716 TI - Septic arthritis as a presentation of Crohn's disease. AB - A 42-year-old man with colonic Crohn's disease presented to the orthopaedic department with septic arthritis of the knee with frank intra-articular pus, which persisted despite repeated joint washouts. This coincided with a symptomatic flare of his colonic Crohns. Imaging revealed a fistulous connection from the proximal sigmoid colon into the pelvis, a psoas abscess, myositis of the musculature around the left pelvic girdle and left thigh and two focal collections almost surrounding the distal femur. The knee symptoms only settled after laparotomy and resection of the diseased sigmoid colon and fistula. This case report demonstrates an unusual presentation of fistulating Crohns disease as septic arthritis. PMID- 21977717 TI - Cystic fibrosis compatible with a full term army engagement. AB - A case of a specialist senior non-commissioned officer with cystic fibrosis (CF) is described. Partial expression of the CF trait is well known and sporadic cases are detected from time to time at recruitment, during recruit training and service. Respiratory symptoms may be mis-diagnosed as self-limiting asthma until a sweat chloride or other specific test for CF is performed. PMID- 21977718 TI - The wars in Africa--Morosi's mountain. PMID- 21977719 TI - Use of transoesophageal echocardiography during the peri-operative period for trauma patients: sprinting before we can walk or run! PMID- 21977720 TI - Creating airway management guidelines for casualties with penetrating airway injuries. PMID- 21977721 TI - The Afghanistan fracture pan. PMID- 21977722 TI - Palliative and end-of-life nursing research now and in the future. PMID- 21977723 TI - Chronic illness, palliative care, and the problematic nature of dying. PMID- 21977724 TI - Participatory knowledge exchange to support palliative care in Chile: lessons learned through global health research. AB - The authors designed a participatory qualitative research study to develop a collaborative partnership between palliative care practitioners in Canada and in Chile. The research goal was to support the provision of palliative care in vulnerable settings through a participatory knowledge exchange process using qualitative and participatory methodologies. The study involved an interprofessional palliative care team from a primary health care centre in Chile and 5 adults receiving palliative care and their relatives. It also involved the participation of registered nurses and allied health professionals from a palliative home care team in Canada. Participatory knowledge exchange activities included teamwork with the primary health care team in Chile and a process of participatory knowledge exchange with palliative care clinicians in Chile and Canada. The study produced qualitative evidence on the efficacy of a process of participatory knowledge exchange with palliative care practitioners from 2 diverse settings. PMID- 21977725 TI - Managing palliative care for adults with advanced heart failure. AB - The purpose of this study was to explore the care processes experienced by community-dwelling adults dying from advanced heart failure, their family caregivers, and their health-care providers. A descriptive qualitative design was used to guide data collection, analysis, and interpretation. The sample comprised 8 patients, 10 informal caregivers, 11 nurses, 3 physicians, and 3 pharmacists. Data analysis revealed that palliative care was influenced by unique contextual factors (i.e., cancer model of palliative care, limited access to resources, prognostication challenges). Patients described choosing interventions and living with fatigue, pain, shortness of breath, and functional decline. Family caregivers described surviving caregiver burden and drawing on their faith. Health professionals described their role as trying to coordinate care, building expertise, managing medications, and optimizing interprofessional collaboration. Participants strove towards 3 outcomes: effective symptom management, satisfaction with care, and a peaceful death. PMID- 21977726 TI - Nurses' moral experience of administering PRN anti-seizure medications in pediatric palliative care. AB - This article explores nurses' decision-making related to the administration of PRN anti-seizure medications to children with long-term seizure disorders in palliative care. Hermeneutic phenomenological inquiry guided by van Manen's approach was the method used. Six nurses participated in interviews. Data analysis revealed that not on my watch was the overarching theme in which nurses engaged in bearing witness, being attentive, creating connectedness, and finding the right thing to do. Four themes emerged: being in the know--what to know and ways of knowing; marking time--waiting and timekeeping; seeking a sense of personal comfort--developing a sense of comfort, experiencing distress, and responding to distress; and making the decision--recognizing a seizure, identifying options, weighing the options, and rethinking the decision. This study reveals the moral dilemmas and resulting moral distress that may be experienced in making this type of decision and advances our thinking about the corresponding tensions and rewards. PMID- 21977727 TI - Core aspects of "empowering" caregivers as articulated by leaders in home health care: palliative and chronic illness contexts. AB - Home-based family caregivers are often assisted by home care services founded upon principles of health promotion, such as empowerment. Using an interpretive approach and in-depth qualitative interviews, the authors examine descriptions of family empowerment by leaders and managers in the field of home health care in the province of British Columbia, Canada. In a culture of fiscal restraint, dying at home, and self-care, participants described how home care nurses empower family caregivers to meet these objectives. This involves educating and informing caregivers, engaging them in planning and decision-making, and reassuring them that their role is manageable and worthwhile. Though some participants viewed providing supports as empowering (e.g., during times of crisis), others viewed them as disempowering (by promoting dependence). Empowered caregivers were characterized as able to provide home care, confident of their capabilities, and believing that their work is positive and beneficial. The long-term goal of empowerment was characterized as client self-care and/or family care and decreased dependence on formal services. PMID- 21977728 TI - How respect and kindness are experienced at the end of life by nursing home residents. AB - Respect and kindness are core principles of nursing practice, yet little is known about how they are experienced by nursing home (NH) residents at the end of life. The aim of this study was to examine the factors associated with being treated with respect and kindness in the last month of life as an NH resident. A retrospective survey of 208 bereaved family members was conducted in 21 NHs located in a city in central Canada. The majority of participants indicated that the resident had always been treated with respect or kindness. However, significant differences emerged, with not all family members believing that their loved one had always been treated with respect or kindness. The apparent lapses in care practices are troubling and indicate that steps must be taken to address them. PMID- 21977729 TI - SevenYears of completing the circle: end-of-life care with Aboriginal families. PMID- 21977730 TI - Selenium, thiobarbituric acid reactive substances, and thyroid hormone activation in broilers supplemented with selenium as selenized yeast or sodium selenite. AB - The objective of this experiment was to compare the efficiencies of sodium selenite (SS) and selenized yeast (SY) supplemented at different doses (0.05 and 0.30 mg Se/kg feed) with respect to plasma glutathione peroxidase (Gpx) activity, extent of oxidative lipid injury, and thyroid hormone activation in broilers during the first four weeks of growth. Results indicate a significant increase in plasma Gpx activity and reduction in thiobarbituric acid reactive substances (TBARS) in all supplemented groups at 4 weeks of age compared to 2-week-old chicks. Plasma thyronine activation was highest in SY supplemented broilers. It can be concluded that in the first 4 weeks of broiler life selenite has a more efficient antioxidative effect which is reflected in lower plasma and liver TBARS values. However, broiler feed supplementation with selenized yeast results in a more proficient conversion of T4 to T3. PMID- 21977731 TI - Identifying a new locus that regulates the development of rete ovarian cysts in MRL/MpJ mice. AB - MRL/MpJ (MRL) is a mouse model for autoimmune disease and develops ovarian cysts with age. The ovarian cysts originate from the rete ovarii, which is considered to be the remnant of fetal mesonephric tubules. In a previous study, we analyzed the genetic background of ovarian cysts by using backcross progenies between MRL and C57BL/6N (B6) mice. By interval mapping, suggestive linkages were detected on several chromosomes (Chrs), and a significant linkage on Chr 14 was designated as MRL Rete Ovarian Cyst (mroc). In the present study, which evaluated 113 F2 intercross progenies, a significant linkage appeared on Chr 6 at the marker position D6Mit188 (likelihood ratio statistic = 18.5). In particular, the peak regions of Chrs 6 and 14, which contain major causative loci by backcross analysis, showed close reverse interaction. From these results, a locus on Chr 6 was identified as mroc2, the second major locus associated with ovarian cyst formation in MRL mice. PMID- 21977732 TI - An H5N1 highly pathogenic avian influenza virus that invaded Japan through waterfowl migration. AB - In 2010, an H5N1 highly pathogenic avian influenza virus (HPAIV) was isolated from feces of apparently healthy ducks migrating southward in Hokkaido, the northernmost prefecture of Japan. The H5N1 HPAIVs were subsequently detected in domestic and wild birds at multiple sites corresponding to the flyway of the waterfowl having stopovers in the Japanese archipelago. The Hokkaido isolate was genetically nearly identical to H5N1 HPAIVs isolated from swans in the spring of 2009 and 2010 in Mongolia, but less pathogenic in experimentally infected ducks than the 2009 Mongolian isolate. These findings suggest that H5N1 HPAIVs with relatively mild pathogenicity might be selected and harbored in the waterfowl population during the 2009-2010 migration seasons. Our data provide "early warning" signals for preparedness against the unprecedented situation in which the waterfowl reservoirs serve as perpetual sources and disseminators of HPAIVs. PMID- 21977733 TI - Isolation of sporocyst broodsacs of the genus Leucochloridium (Leucochloridiidae: Trematoda) from the intermediate host, Succinea lauta, in Japan. AB - Green- or brown-striped trematode sporocyst broodsacs typical of Leucochloridium infecting the ocular tentacles of a land snail, Succinea lauta, were collected in Abashiri, Hokkaido in northern Japan (N43 degrees 59', E144 degrees 14') in June of 2000 and 2001. The metacercariae isolated from the sporocyst broodsac were morphologically identified as Leucochloridium spp. (Leucoclhoridiidae Poche). This report is the first to describe evidential specimens of the sporocyst broodsac of the genus Leucochloridium Carus, 1835, infecting the intermediate host in Japan, suggesting that Leucochloridium spp. completes their life cycle in Hokkaido, Japan. PMID- 21977734 TI - Nursing input is essential. PMID- 21977735 TI - Climate of fear at Stepping Hill after investigation takes new turn. PMID- 21977736 TI - NHS waiting times could rise if private patient funds limit ditched. PMID- 21977737 TI - Conference cancellations could affect professional development. PMID- 21977738 TI - Nurses successful at diverting gang members to youth support. PMID- 21977739 TI - Controversial NHS reforms near the final stage of their journey. PMID- 21977740 TI - When the dust settled. AB - Contrary to common belief, hospitals were inundated with casualties after the 9/11 terrorist attacks. One of them, St Vincent's in New York, has since closed and nurses are campaigning for a new hospital to be built in its place. PMID- 21977741 TI - Counsel with care. AB - Studies have shown that mass counselling after a disaster is unnecessary, but a minority of people benefit from specialist support. PMID- 21977742 TI - Influence of location on a good death. AB - With the recent emphasis of the Department of Health on reducing unnecessary hospitalisation at the end of life and improving community care for people dying at home, it could be assumed that dying at home is the gold standard. However, healthcare professionals should be able to give a patient choice over where they die, whether that is at home, in hospital or in a hospice. This article asks the reader to consider whether location of death has an influence on the quality of death. PMID- 21977743 TI - Emollient therapy for dry and inflammatory skin conditions. AB - Most nurses will encounter patients with dry skin conditions such as atopic eczema and psoriasis in their everyday practice. Emollients can be beneficial for most dry skin conditions, although they are widely underused. Increased knowledge and awareness of the benefits and optimal use of emollient therapy can improve patient care and outcomes. PMID- 21977744 TI - Assessment and management of atopic eczema in children. AB - Atopic eczema is a chronic inflammatory itchy skin condition caused by a defect in skin barrier function. It is common in infants and children and may continue into adulthood. Assessment of eczema in children must be holistic, taking into account physical and psychosocial factors. There is no cure for eczema and treatments aim to control the disease. First-line treatment consists of emollients, but many children will also require the use of topical corticosteroids and other treatments as appropriate. Healthcare professionals have an important role to play in educating children, and their parents and carers, in the management of atopic eczema to prevent exacerbation of the condition and improve quality of life. PMID- 21977745 TI - Diabetic ketoacidosis. PMID- 21977746 TI - Welcome to the club. PMID- 21977747 TI - All the fun of the jobs fair. PMID- 21977748 TI - The highest possible rung. PMID- 21977749 TI - If it works, why change it? PMID- 21977750 TI - Health minister backs move to greater regional wage flexibility. PMID- 21977751 TI - Many of the failings at mid staffs are evident in the NHS, says CNO. PMID- 21977752 TI - College vows to persist in battle to change government health bill. PMID- 21977753 TI - Jobs hang in the balance as care homes fail to find new operators. PMID- 21977754 TI - 'I am an optimist--our efforts are making a difference'. PMID- 21977755 TI - Are nursing staff as busy in summer as winter? PMID- 21977756 TI - Sick of feeling lonely. AB - Loneliness in older people poses a huge health risk, say campaigners. But there are steps nurses can take to spot and address the problem. PMID- 21977757 TI - Enterprising ideas. AB - The transfer of NHS community services to social enterprises is controversial. Small enterprises are working well, but their future is uncertain. PMID- 21977759 TI - Changing course. AB - Nurse training in the 1950s and 1960s was hierarchical but it focused on patient care and providing role models. PMID- 21977758 TI - A stick to beat MRSA. AB - Trafford Healthcare NHS Trust's infection control scheme has resulted in more than two years without a case of MRSA bloodstream infection. PMID- 21977760 TI - Introduction to the stroke series. PMID- 21977761 TI - Effect of stroke on family carers and family relationships. AB - The effects of stroke on families are considerable. Family members may struggle to adapt to a care-giving role, and relationships between stroke survivors and those closest to them are often altered by the illness. This article provides an overview of the effects of stroke on family dynamics and identifies interventions to support stroke survivors and their families during this difficult time. PMID- 21977762 TI - Care of adult patients with a temporary tracheostomy. AB - The insertion of a temporary tracheostomy is a common procedure in the critical care environment. This article aims to explore the evidence relating to the nursing care required for a patient with a temporary tracheostomy in a critical care or acute ward setting. The article focuses on the insertion of a tracheostomy as a planned intervention to improve or enable patient recovery, rather than an emergency procedure for airway obstruction. The procedure is not without risk and aftercare is vital to ensure the patient remains safe and the procedure aids recovery and promotes comfort. PMID- 21977763 TI - Dementia care. PMID- 21977764 TI - Losing total recall. PMID- 21977765 TI - Time to take stock of support contribution. PMID- 21977766 TI - Working in a war zone. PMID- 21977767 TI - Treating sleep disorder improves stroke recovery, study finds. PMID- 21977768 TI - Relationships between biophysical and psychosocial outcomes following minor stroke. AB - This descriptive correlational study examined relationships between mild stroke functional and psychosocial outcomes over the early post-discharge period among dyads of mild stroke patients (n=38) and their spousal caregivers (n=38). We measured patients' functional scores using the modified Rankin Scale; patients' and caregivers' quality of life (QoL) using Stroke Impact Scale and Short-Form 36 respectively, mood using the Beck Depression Inventory-II, and marital function scores using the Family Assessment Device. Spousal caregivers also completed the Bakas Caregiving Outcomes Scale as a measure of caregiver strain. The average age of stroke patients was 64 years and of spousal caregivers 58 years. All stroke patients were male; all spousal caregivers female. At three months post discharge, patient functional status scores had significantly improved from discharge (p=0.026) with a corresponding increase in QoL scores (p=0.012). Functional status was significantly correlated with patient perceptions of QoL at three months (r=.014, p=0.024) and spousal caregiver perceptions of physical domain QoL (r=.-.397, p=0.014). Spousal caregivers' mood at three months post discharge was strongly correlated with their perceptions of marital satisfaction (r=.578, p=0.000) and caregiver strain (r=-.620, p=0.000). In preparing patients for discharge following mild stroke, nurses must consider the psychological and social implications of the recovery process over time for both the patient with stroke and their spousal caregivers. PMID- 21977769 TI - Pediatric posterior fossa syndrome (PFS): nursing strategies in the post operative period. AB - Posterior fossa syndrome (PFS), or cerebellar affective syndrome, is a severe and distressing complication that may occur in up to 40% of children following posterior fossa brain tumour resection. Depending on the type, size and location of the tumour, clinical presentations of PFS can vary widely. Patients may exhibit mutism, emotional lability, high-pitched crying (sole form of vocalization), poor oral intake, extreme irritability, decreased motor movements and urinary retention. Typically, the onset of the syndrome occurs one to five days after surgery resulting in a devastating situation for patients and families. PFS may persist up to four months with resultant long-term impairments and permanent disability. The development and initiation of nursing strategies for patients with PFS is critical. They support family coping decrease stress and anxiety after surgery and, ultimately, enable optimal patient and family outcomes. By managing acute symptoms, promoting rehabilitation and initiating strategies to restore behavioural and physiological function, neurosurgical nurses play an essential and instrumental role. PMID- 21977770 TI - Transition from pediatric to adult health care for young adults with neurological disorders: parental perspectives. AB - PURPOSE: With advances in pediatric health care, many adolescents with complex chronic neurological conditions live well into adulthood. As such, the movement toward adult health care services is an expected and desired outcome of pediatric care. When the young adult has an intellectual impairment in addition to a complex chronic neurological condition, parental involvement is critical in the transition process, as these young adults are unable to make informed decisions independently and require significant guidance from caregivers. Thus, the transition process should address not only the direct health care needs of the young adult, but also the needs and concerns of the parents who are instrumental in guiding that process. The objective of this study was to identify salient issues confronting these parents. METHODS: A qualitative interpretive design was used to gain an in-depth understanding of parents'perceptions of their young adults' transition process from a pediatric to an adult health care setting. Data were analyzed using the constant comparative method, in which interview data were simultaneously collected and analyzed throughout the data collection process. Purposive sampling was used to interview 17 parents of 11 young adults who had transitioned to an adult health care setting. RESULTS: Findings suggest that parents perceived a tremendous sense of abandonment from the heath care team during the transition process. They experienced a sense of loss, fear and uncertainty, as they navigated the transition of their young adult. Parents believed that what hindered the transition process was a lack of sufficient coordination within the health care system, the vulnerability of the young adult at the time of transition, the lack of appropriate resources in the adult health care system given the unique and multifaceted needs of the young adult, and their own tenuous health status. The transition process was felt to be facilitated by the parent's resourcefulness, family support and ability to establish new relationships within the adult health care setting. CONCLUSIONS: This study has provided a greater understanding of parental perceptions of transition care for young adults with a complex chronic neurological disorder who have an intellectual impairment. The emotional toll on the parents is tremendous and requires thoughtful consideration when planning the transition process for these young adults. Although all parents acknowledged the hardships and adversity they faced during the process were immense, they all felt that with better guidance and improved resources, the experience for future families could be a positive and satisfying experience. PMID- 21977771 TI - [Advice and comfort not just from the pastor]. PMID- 21977772 TI - [Persons with a mental handicap in an acute hospitals. There are ways to communicate]. PMID- 21977773 TI - ["I believe we've become more vigilant" (interview by Margrit Bachi)]. PMID- 21977774 TI - [Medicalization of everyday life: on the borderline between health and illness]. PMID- 21977775 TI - [Position paper "Perspective 2020". Innovative models of prevention and health care]. PMID- 21977776 TI - [Nursing interventions in alcohol related addictions: nursing has a great potentials]. PMID- 21977777 TI - [Health care management interest group: sensitizing for a healthy work place]. PMID- 21977778 TI - [Home for the aged in Chruzmatt in Hitzkirch: exemplary health promotion]. PMID- 21977779 TI - [Green care: renaissance of garden therapy]. PMID- 21977780 TI - [Neonatal intensive care: optimizing pain management in newborn infants]. PMID- 21977782 TI - [Hats off!]. PMID- 21977783 TI - [Sexual diversity and school health: the largely unknown vulnerabilities]. PMID- 21977784 TI - [Dealing with mental illness: the emergence of caregivers and citizens]. PMID- 21977786 TI - ["Persecuted" patients: the little father of nursing care]. PMID- 21977787 TI - [Healing means communicating]. PMID- 21977788 TI - [Small intestine ileus: corpus delicti in a fruit handler]. PMID- 21977789 TI - [Community acquired pneumonia: how to proceed when the antibiotic does not help?]. PMID- 21977790 TI - [Sore throat, fever and swallowing difficulty: what compresses the pharynx?]. PMID- 21977792 TI - [Naturopathy consultation. Heart failure]. PMID- 21977791 TI - [Young patient with mild hypertension: angiotensin inhibitor or beta blocker?]. PMID- 21977793 TI - [Good family practice. You have the experience, we provide the know-how]. PMID- 21977794 TI - [Flu-like illness--how to rule in and manage influenza]. PMID- 21977795 TI - [Conservative management of coronary artery disease]. PMID- 21977796 TI - [Atrial fibrillation: what the GP needs to know]. PMID- 21977797 TI - [Obesity: diagnosis and therapy]. PMID- 21977798 TI - [Helicobacter pylori--diagnosis and treatment]. PMID- 21977799 TI - [Venous thrombosis--diagnosis and treatment]. PMID- 21977800 TI - [How to prevent and to treat osteoporosis successfully]. PMID- 21977801 TI - [Pressure ulcers: prevention and treatment]. PMID- 21977802 TI - [Early diagnosis and treatment of dementia]. PMID- 21977803 TI - [Depression and anxiety in the elderly--diagnosis and treatment]. PMID- 21977804 TI - [Hypertensive and organ damage. Dementia and cognitive impairment]. PMID- 21977805 TI - Effects of needle-knife therapy on iNOS activity and NO content in skeletal muscles in the L3 transverse process syndrome model rat. AB - OBJECTIVE: To study on relationship of inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) content in the injured local soft tissue with injured degrees of the soft tissue in the third lumbar vertebrae (L3) transverse process syndrome model rat and to observe the effect of needle-knife therapy. METHODS: One hundred and sixty male SD rats were randomly divided into normal group, model group, aminoguanidine (AG) group, needle-knife group, 40 rats in each group. The L3 transverse process syndrome rat model was established, and after treatment of needle-knife and AG iNOS activities and NO contents and histomorpholocal changes in the soft tissues around L3 transverse process on 1, 3, 7 and 14 days were observed in the groups. RESULTS: Compared with the normal group, iNOS activity and NO content in the model group were significantly increased (P < 0.01); Compared with the model group, iNOS activities and NO contents were significantly decreased in both the needle-knife group and the AG group (both P < 0.01); And both iNOS activities and NO contents were identical with both local inflammation response and injured degrees of the injured tissue in the groups. CONCLUSION: Needle-knife therapy can significantly inhibit generation of NO, alleviate inflammatory response and injured degree of the injured soft tissue, improve microcirculation, prevent formation of pathological scar tissue, and promote repair of the chronic soft tissue injury. PMID- 21977806 TI - The proteomic research of the cure of experimental diabetes deafness by granules of eliminating phlegm and removing blood stasis. AB - OBJECTIVE: Observing the expression changes of serum proteome in model rats after intervention of the Granules of Eliminating Phlegm and Removing Blood Stasis ((see text) also known as GEPRB), screening outand identifying the differentially expressed proteins by mass spectrometry and bioinformatics analysis, discussing the molecular mechanism of control the Diabetes deafness by GEPRB. METHODS: By use of proteomics technology, the serum protein serum proteome of the control group, model control group, Duxil and each observation group were observed for 2 DE gel pattern matching, and the difference in the relative content of 2 times was chosen for the differentially expressed proteins. Identification of differentially expressed proteins by MALDI-TOF MS/MS, the authors further analysis the phosphorylation, subcellular localization, interaction, direct regulation, and transmembrane of the differences proteins by the way of bioinformatics analysis. Sixty SPF level SD rats elected in diabetic rats model group (abbreviated as DM group) were be randomly divided into 5 groups based on random number sheet, namely model control group, positive drug control group (Du ke-xi group) and Mai-tong-fang high, medium and low dose group respectively. In addition, set of normal control group. 10 rats in each group. RESULTS: By Coomassie brilliant blue staining, identified 51 differential protein spots dug from 2-D gel by mass spectrometry, successfully identified 13 non-redundant proteins. Most of the identified proteins were secreted protein and belong to different protein families. There were about 12 proteins have the transmembrane region from the authors' result, ten of them were plasma membrane proteins. CONCLUSION: It's suggesting that 13 differential proteins is most likely the protein response to GEPRB in vivo, these proteins may play key role for the treatment of GEPRB to Diabetes deafness. The two highly differentially expressed proteins Apolipoprotein E (apoE) and C3 may be a potential drug target of GEPRB. PMID- 21977807 TI - Effects of zuogui pill (see text) on Wnt singal transduction in rats with glucocorticoid-induced osteoporosis. AB - OBJECTIVE: To reveal the mechanism of Zuogui Pill (see text) in treatment of glucocorticoid-induced osteoporosis from the angle of the Wnt signal transduction pathway and to provide further experimental evidence for expounding the scientific connotation of "the kidney dominating the bones" in TCM. METHODS: Forty-two male Wistar rats were selected and randomly divided into three groups, control group (n = 12), model group (n = 15) and Zuogui Pill group (n = 15). Form the beginning, The rats were injected dexamethasone for eight weeks to make the model of osteoporosis, and the Zuogui Pill were administered intragastrically to the rats of Zuogui Pill group for eight weeks. The relative morphological parameters were measured in the undecalcified tibial slices. And the protein expression levels of Wnt1, LRP-5 and beta-catenin in rat tibial osteoblasts (OB) and bone marrow stromal cells (BMC) were detected by immunohistochemistry. RESULTS: Compared with the control group, TBV% and TFS% decreased significantly, while TRS% increased significantly, and the protein expression of Wnt1, LRP-5 and beta-catenin in OB and BMC decreased significantly in the model group. And compared with the model group, TBV% and TFS% increased significantly, and expression levels of Wnt1, LRP-5 and beta-catenin proteins increased significantly in the Zuogui pill group. CONCLUSION: Zuogui Pill can prevent and treat glucocorticoid-induced osteoporosis in rats by up-regulating the expression of the key signal molecules Wnt1, LRP-5 and beta-catenin in Wnt signal transduction pathway. PMID- 21977808 TI - Synergetic effect of yihuo qingyi decoction (see text) and recombinant staphylokinase in treatment of severe acute pancreatitis of rats. AB - OBJECTIVE: To investigate the effect of recombinant staphylokinase (r-Sak) and the Chinese medicine Yihuo Qingyi Decoction ((see test) Herbal decoction for severe acute pancreatitis) in the treatment of the severe acute pancreatitis (SAP) in rats, and to observe the synergistic effect of the two. METHODS: One hundred and sixty-two adult male SD rats with the body mass of 250-280 g were randomly divided into the following 5 groups: sham operation group (n = 18), control group (n = 36), Yihuo Qingyi Decoction treatment group (n = 36), r-Sak treatment group (n = 36), and Yihuo Qingyi Decoction plus r-Sak treatment group (n = 36). The SAP ratmodel was prepared by retrograde injection of 5% sodium taurocholate into the cholangiopancreatic duct. Two days before modeling, Yihuo Qingyi Decoction was intragastrically administrated, and r-Sak was intraperitoneally injected. The survival rate within 18 h after modeling was determined. The pancreatic blood flow, the weight of ascites, and the serum amylase and lipase were investigated at 6 h, 12 h, and 18kh after modeling, and the pancreatic tissue was examined under light microscopy to see its pathological change. RESULTS: The 18 h survival count of group A, B, C, D and E rats was 9, 2, 6, 7 and 8 respectively. After r-Sak and Yihuo Qingyi Decoction intervention, the serum amylase and lipase and the weight of ascites were significantly decreased, especially in group E.18 h after modeling, the level of the serum amylase and lipase and the weight of ascites in group E was 1 100 +/- 118 U x L(-1), 1 000 +/ 150 U x L(-1) and 13.40 +/- 1.80 g respectively, obviously lower than that of group B (P < 0.05). After SAP was induced, the pancreatic blood flow showed a tendency to decrease, but the decrease extent in the treatment groups was smaller than that in the control group. 18h after modeling, the pancreatic blood flow in group B and group E was 30.16 +/- 8.96 mL x 100 g(-1) x min(-1), and 129.10 +/- 42.58 mL x 100 g(-1) x min respectively, there was significant difference (P < 0.05). The pathological change of the pancreatic tissue was alleviated in the treatment groups. CONCLUSION: Both r-Sak and Yihuo Qingyi Decoction play a beneficial role in the treatment of rat SAP and there is a synergistic effect between the two. PMID- 21977809 TI - Effects of suxiao jiuxin pill (see test) on oxidative stress and inflammatory response in rats with experimental atherosclerosis. AB - OBJECTIVE: To observe the preventive role of Suxiao Jiuxin Pill (see text) on atherosclerosis (AS) and to probe into the mechanism in the atherosclerosis rat model. METHODS: The AS rat model was established by a high fat diet and a large dose of calcium (vitamin D3, 0.6 million U/kg, i.p, once). Sixty healthy male adult Sprague-Dawlay (SD) rats were randomly divided into 6 groups, a normal control group (N), a model group (M), a SX low dose group (SXL), a SX middle dose group (SXM), a SX high dose group (SXH), and an atorvastatin group (ATO) (n = 10 in each group). The rats in the treatment groups were given with the specific drugs from the first day by oral administration, and the normal control group and the model group were given with normal saline for 12 weeks. Afterwards, the content of malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and the content of oxidized low density lipoprotein (ox-LDL) in the serum were detected. In addition, the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) proteins were tested by Western-blot method. RESULTS: The serum ox-LDL and MDA level significantly decreased, SOD activity increased in the SX middle, high dose groups and the atorvastatin group compared to the model group (all P < 0.05). While the expression of PPARgamma and NF kappab proteins significantly decreased in the SX low, middle, high dose groups and the atorvastatin group compared to the model group (all P < 0.01), with the best effect in the SX high dose group .These results indicate that SX could elevate the activity of serum SOD, decrease serum level of MDA and ox-LDL, and reduce the expression of PPARgamma and NF-kappaB proteins. CONCLUSION: SX plays an important role in anti-inflammation and inhibition of oxidative stress, which possibly are the mechanism of its preventing and treating atherosclerosis. PMID- 21977810 TI - Effect of electroacupuncture on serum copper, zinc, calcium and magnesium levels in the depression rats. AB - OBJECTIVE: To investigate effect of electroacupuncture (EA) on serum copper, zinc, calcium and magnesium levels in the rat models of depression. METHODS: Forty healthy SD male rats were divided into a normal group, a model group, an EA group, and a maprotiline group, 10 in each with completely random. The depression models were prepared with isolated chronic unpredictable stress method in the latter three groups. EA was given at Baihui (GV 20), Yintang (EX-HN3), Fenglong (ST 40), and Taichong (LR 3) in the EA group from the second day of modeling, once every other day, 15 min each time. The maprotiline group was administered intragastrically suspension of maprotiline (10 mg/kg), once each day. After treatment for 3 weeks, serum copper and zinc levels were detected with atomic absorption method, and the serum calcium with Arsenazo III method and magnesium with MTB method. RESULTS: Compared with the normal group, the serum copper level (3.90 +/- 1.20 mmol/L) significantly increased and the serum zinc level (2.08 +/- 0.44 mmol/L) significantly decreased in the model group (P < 0.05). Compared with the model group, the serum copper level (2.62 +/- 1.03 mmol/L) significantly decreased, the serum zinc level (2.55 +/- 0.38 mmol/L) significantly increased (P < 0.05), but the serum calcium and magnesium levels did not significantly change in the EA group and the maprotiline group. CONCLUSION: EA can regulate the change of copper and zinc levels in the body induced by depression, which is possibly one of mechanisms of effectively improving depression symptoms. PMID- 21977811 TI - The short-term therapeutic effects of TCM for IgA nephropathy in children. AB - OBJECTIVE: To evaluate the short-term therapeutic effects of TCM for IgA nephropathy in children. METHODS: Sixty-two children with primary IgA nephropathy diagnosed for the first time by renal biopsy in the authors' hospital were randomly divided into a group of 34 cases treated with both TCM and Western medicine and a group of 28 cases treated with Western medicine for six months. The improvements in urinary protein and red blood cell (RBC) were observed and the scores for TCM symptoms and signs were evaluated after 3 months and 6 months of treatment. RESULTS: There was no significant difference in the total effective rate between the two groups (chi2 = 4.743, P > 0.05 after treatment for 3 months; and chi2 = 1.953, P > 0.05 after treatment for 6 months). However, the cure plus marked effect rate in the group treated with both TCM and Western medicine was higher than that in the group treated with Western medicine (71.9% vs 45.5%, P < 0.05 after treatment for 3 months). At the end of treatment, significant difference were found in the effective rate (9.3% vs 10.5%, chi2 = 9.653, P < 0.01) and in the total score (0.81+1.18 vs 3.42 + 2.52, t = 4.19, P < 0.001) between the two groups. CONCLUSION: Treatment with both TCM and Western medicine can effectively improve the TCM symptoms and signs in child patients with IgA nephropathy, and alleviate hematuria and albuminuria. PMID- 21977812 TI - Effect of busui shengxue granule (see text) on chronic aplastic anemia patients' hematopoietic adhesion molecule VLA-6/CD49f and its ligand laminin. AB - OBJECTIVE: To observe the effect of Busui Shengxue Granule ((see text) Herbal granule for replenishing marrow to produce blood) on chronic aplastic anemia (CAA) patients' integrin alpha 6 (VLA-6/CD49f) and laminin (Ln). METHODS: Sixty five patients were divided into experimental group and control group through random number table. There were 34 patients, 17 were male and 17 female, aged 2 67, with a medianage of 30.2 +/- 8.6, in the experimental group, including 17 patients of kidney-yin deficiency and 17 of kidney-yang deficiency, treated by Busui Shengxue Granule. There were 31 patients in the control group, 16 were male and 15 female, aged 4-65, with a medianage of 31.2 +/- 8.0; administered Zaizhang Shengxue Tablet (see text) Herbal tablet for chronic aplastic anemia). Both groups were treated for six months and compared with 10 normal persons after the treatment. Flow cytometry was adopted to detect the change in the expression of VLA-6/CD49f, receptor in mononuclear cells of CAA patients and normal persons. Enzyme-linked immunosorbent assay was applied to detect the expression of peripheral serum Ln. RESULTS: CAA patients' VLA-6/CD49f was in the state of low expression and Ln in the state of high expression. After the treatment, both VLA 6/CD49f and Ln were regulated to some extent and the change in the experimental group was better than that of the control group. Compared with the kidney-yin deficiency patients, those indices of kidney-yang deficiency patients were easier to correct. CONCLUSION: The VLA-6/CD49f and Ln expressions of CAA patients are abnormal. The treatment with Busui Shengxue Granule makes both of them improved. PMID- 21977813 TI - Effects of zao huang mixture (see text) on the expressions of TGF-beta1 and Col IV in human glomerular mesangial cells cultured in high glucose environment. AB - OBJECTIVE: To investigate the effect of Zao Huang Mixture (see text) on expressions of growth factor-beta1 (TGF-beta1) and collagen IV (Col IV) in human glomerular mesangial cells (GMC) cultured in high-glucose environment. METHODS: After primary culture of GMC, in vitro culture was carried out in normal group, high glucose group and high glucose medium with ZHM of different concentrations, and the expressions of TGF-beta1 and Col IV in the GMC group and in ZHM group were detected at 24 and 48 h respectively. RESULTS: Compared with the normal group, expressions of TGF-beta1 and Col IV significantly increased at 24 h, 48 h in the high glucose group (all P < 0.01); Compared with the high glucose group, the expressions of TGF-beta1 and Col IV in all the ZHM groups significantly decreased at 24 h, 48 h (P < 0.05 or P < 0.01). CONCLUSION: ZHM may modulate the process of diabetic nephropathy by changing the expression of TGF-beta1 and Col IV in glomerular mesangial cells. PMID- 21977814 TI - The safety-influencing factors in use of the tonics of Chinese medicine: a meta analysis based on the case reports in periodicals. AB - OBJECTIVE: To identify the possible safety-influencing factors in use of the tonics of Chinese medicine. METHODS: The related case reports published in periodicals published from 1949 to 2006 were analyzed with the bibliometrics method. Possibility on safety assessment of Chinese materia medica was discussed as well with the method of link analysis. RESULTS: The total number of the tonics selected for the present study was 101, including 44 single drugs and 46 set prescriptions with adverse drug reactions (ADR) found in these tonics. It was found that ADR of 10 single drugs and 29 preparations were not specified in authoritative Chinese materia medica monographs. Among all the set prescriptions, the problem of injection has been standing on the top. Statistical analysis on single factor demonstrates that the most frequently referred ADR come from drug abuse (accounting for 29.20%), and overdose (24.54%). CONCLUSION: The safety problem of injection remains in a trend of robust growth at least for a period of time, thus reappraisal of the safety issue for the tonics of injection is imperative. It is essential for the public to take doctor's advice to guarantee safe administration of the tonics, especially for the patients with allergic constitution or those suffering from the liver and heart diseases. PMID- 21977815 TI - Study on the sequence in formulating standards for acupuncture and moxibustion. AB - OBJECTIVE: To study which items need the formulation of national standards and which standards should be first formulated. METHODS: Apply the method of the questionnaire survey to collect data, and the statistical analysis adopt the frequency and weighted average method. RESULTS: Propose the items of acupuncture and moxibustion which need the urgent formulation of standards and the sequence in the formulation of standard items. CONCLUSION: Provid important bases for the follow-up report of national standard items and avoid temporary formulation of standards without plan. PMID- 21977816 TI - Effects of tai chi on lower-limb myodynamia in the elderly people: a meta analysis. AB - OBJECTIVE: To assess the effects of Tai Chi (Chinese shadow boxing exercise) for improving the lower-limb muscle strength in elderly people. METHODS: The PUBMED database (from 1950), EMBASE-ASP database (from 1974), Cochrane Library (from 1991), Elsevier sciences database (from 1990), OVID full text database (from 1997), Springer-link database (from 1997), The National Research Register database, ISI Web of knowledge (from 1963), Chinese Medical Citation Index/Chinese Medical Current Contents (CMCI/CMCC, from 1989), China Knowledge Resource Integrated Database (CNKI, from 1915), VIP database (from 1989), and Wanfang database (from 1977) have been searched only for the English and Chinese literatures updated to 10-30-2010. Two researchers independently assessed the methodological quality of studies, extracted and checked the data one another according to the include/exclude standards. Disagreement was resolved by discussions or with the third person. The Review Manage Software 5.0 was used for Meta-analysis. RESULTS: Eventually, 2 randomized controled studies and 2 non randomized controled studies met the inclusion criteria, with 163 subjects involved in the present meta-analysis. The meta-analysis demonstrated that Tai Chi exercise could improve the ankle flexor/extensor muscle strength and the knee extensor/flexor muscle strength, tested with an isokinetic dynamometer. The limb muscle strength increased significantly after Tai Chi exercise (P < 0.01). CONCLUSION: The meta-analysis favours Tai Chi exercise for improving the lower limb muscle strength in the older people. PMID- 21977817 TI - The TCM pattern of the six-zang and six-fu organs can be simplified into the pattern of five-zang and one-fu organs. AB - OBJECTIVE: To simplify the TCM pattern of the zang-fu organs. METHODS: A database of zang-fu syndromes was established. The relationship between the zang-fu syndromes was analyzed by means of frequency analysis, association rule, and phi coefficient correlation. RESULTS: The six zang-fu organs of the heart, liver, spleen, lung, kidney, and stomach prove to be the main components of the zang-fu pattern. The large intestine, small intestine, gallbladder, bladder, triple energizer, and pericardium have strong association and positive correlation with the above-mentioned six zang-fu organs, and their clinical symptoms can all be included into the symptoms of these six zang-fu organs. CONCLUSION: The traditional TCM pattern of six-zang and six-fu can be simplified into five-zang and one-fu. PMID- 21977818 TI - Evidence-based Chinese medicine for rheumatoid arthritis. AB - Chinese medicine (CM) has long been adopted for treatment of rheumatoid arthritis (RA). CM approaches RA as it does for other diseases by holistic treatment, focusing on the whole body condition, and giving a variety of applications in accordance with the stage and symptoms of the disease. For seeking the best evidence of CM in making decisions for the care of RA individual patients, a number of clinical studies have been conducted in China to gain credibility with the researchers' unremitting efforts. But the heterogeneity in many of these clinical trials and the low quality of design in some previous studies present an obstacle to the meaningful systematic reviews (SR) and meta-analysis. Some favorable results in improvement of response to biomedicine and reduction of severe adverse reactions of conventional RA therapy should be carefully interpreted and need further research. Fortunately, more appropriate quality assurance and control of CM researches are raised for the implementation of CM in RA therapy to pave the evidence-based way. Guidelines for the diagnosis and treatment of RA recommend evidence to the clinicians. In future, randomized controlled trials (RCT) with smart and flexible design as a good approach to evaluate the effectiveness will be widely used in CM for RA clinical study, with better research methods suitable for certain CM clinical researches. The development of evidence-based CM for RA will be full of challenge and opportunity, but we have full confidence. PMID- 21977819 TI - Yin-yang balance therapy on regulating cancer stem cells. AB - Researches have shown that cancer stem cells, regulated by the niche where they reside, are the roots of oncogenesis, relapse and metastasis. To date, very few treatments have targeted on cancer stem cells. The authors study that the regulated factors in the niche share the characteristics of yin-yang in the theory of traditional Chinese medicine, which has confirmed its therapeutic effects in the prevention and treatment of cancer. So the authors presume that the mechanisms of traditional Chinese medicine on the prevention and treatment of cancer may be related to the yin-yang balance of the niche of cancer stem cells. PMID- 21977820 TI - [Taking care of the elderly together]. PMID- 21977821 TI - [Older people who are 'weary of life': their expectations for the future and perceived hopelessness]. AB - There has been a debate for over a decade in The Netherlands about whether physicians should be allowed to provide assistance with suicide to older people who are 'weary of life'. Actual knowledge about these older people is missing in this debate. The purpose of this article is to explore and discuss the expectations older people who are 'weary of life' have of their future, and to what extent they perceive their suffering as hopeless. In this qualitative study, 31 older people who were 'weary of life' were interviewed. The results of this study show that most respondents who were 'weary of life' did not plan to end their life within a short time frame. The burden to their loved ones played a large role in their decision in addition to the awareness of still having reasons to live. Most respondents tried not to think too much about the future, and hoped death would come soon. Most respondents could not name a condition that would diminish their wish to die, that they also found desirable and feasible. The results of this study suggest that people who develop thoughts about death do so when they give up finding solutions to improve their situation. PMID- 21977822 TI - [Changes in the quality of life of older people living at home: does type of care play a role?]. AB - PURPOSE: To determine whether a change in physical, psychological and social dimensions of quality of life of older people living at home is associated with receiving formal care, compared to informal care and no care. METHOD: Data from the observation cycles in 1998 and 2001 of the Longitudinal Aging Study Amsterdam (LASA) were used. Older people receiving formal homecare in 1998 were compared to older people receiving informal care and to older people receiving no care at all in 1998 on subjective scores on 3-year changes in self-perceived health, loneliness, positive affect and satisfaction with life. The data were analysed using linear regression analysis and ANOVA. RESULTS: In all groups there is a change for the worse between 1998 and 2001 in the four aspects of quality of life. Self-perceived health declines significantly more in the group receiving formal care compared to the group without care, but this is explained by a higher score on functional limitations in 1998. Loneliness increases significantly more in the group receiving formal care, even after correction for confounders. In the group receiving formal care the satisfaction with life decreases significantly more compared to the group receiving no care and the group with informal care. An interaction effect with gender was found, showing that after correction for confounders this difference is maintained for the women but not for the men. There is no significant difference between the three care groups regarding changes in positive affect. CONCLUSION: Older men and women who receive formal home care experience an increase in loneliness, and older women who receive formal care experience less satisfaction with life, compared to women who receive informal care or no care. Future research should confirm these results and investigate the mechanisms underlying these changes. PMID- 21977823 TI - [Generalized or targeted screening for carriage of MRSA on admission to a geriatric hospital]. AB - OBJECTIVES: To confirm previously risk factors for MRSA carriage in our geriatric patient population and to suggest a simplified risk score with a combination of these risk factors, to test the Novel Score and to check if a targeted MRSA screening on admission is possible to reduce the screening workload and cost. DESIGN: a prospective in-hospital cohort study. SUBJECTS: 1125 geriatric patients were screened for MRSA carriage within 24 hours after admission to a geriatric hospital. METHODS: Risk factors, based on recently published risk scores (Preop Score and Ger Score) were determined. RESULTS: Prevalence of MRSA carriage was 8.44%. In a multivariate analysis age > or = 87 year (OR 1,864; 95% CI 1,145 3,035), presence of a long-term catheter (OR 2,813; 95% CI 1,562-5,065) and prior carriage of MRSA (OR 13,25; 95% CI 8,007-21,926) remained predictors of MRSA carriage. The Novel Score (cut-off > or = 1) had a sensitivity of 73.7%, a specificity of 64%, PPV 15.9%, NPV 96.3% and AUC of 0.688. The Novel Score allows reduction of the screening load by 57.2%, but misses 26% of positive cases. 16% of MRSA carriers develop an infection that needs to be treated with vancomycin. CONCLUSION: With targeted MRSA screening on admission based on a risk score a substantial reduction of workload and costs is possible compared to generalized screening for MRSA. Because MRSA carriers can be missed with a risk score, the epidemiological context and the risk of transmission and infection with MRSA must be taken in to account when introducing a targeted screening. PMID- 21977825 TI - Which factors actually influence the development and progression of overt nephropathy in Nigerian diabetics? AB - OBJECTIVE: To determine the risk factors predisposing Nigerian diabetics to overt nephropathy with a view to developing strategies for its prevention. DESIGN: case control study. SETTING: Tertiary care hospital, a major nephrology referral centre in Nigeria. SUBJECTS: 30 diabetic nephropathy (DN) patients and 32 age and sex-matched diabetic patients without nephropathy. MATERIALS AND METHODS: 30 diabetic nephropathy (DN) patients with chronic renal failure who have been diabetic for a minimum of five years and satisfied the inclusion criteria for the study were compared with 32 age and sex-matched diabetic patients without nephropathy. Their socio-demographic parameters, clinical and laboratory profiles were determined and compared. RESULTS were analysed using the statistical package for social sciences version 10. Chi-square test, logistic regression analysis and Spearman's rank correlation coefficient were used, p-value < 0.05 was considered as significant. MAIN OUTCOME MEASURES: The study sought to compare socio demographic, clinical and biochemical data between diabetic patients with overt nephropathy and those without. RESULTS: Duration of diabetes, blood pressures and blood sugar levels were significantly higher in DN patients than the controls (p < 0.05). A family history of renal disease, socio-economic status, cigarette smoking, body mass index and total serum cholesterol did not distinguish between DN patients from controls (p > 0.05). Systolic blood pressure positively correlated with serum creatinine (r = 0.057, p < 0.001) and duration of DM (r = 0.284, p = 0.02). There was a constellation of clinical features viz: retinopathy, peripheral neuropathy and left ventricular hypertrophy, which were significantly associated with DN (p < 0.05). CONCLUSIONS: Prolonged duration of diabetes, hypertension, retinopathy, and peripheral neuropathy, left ventricular hypertrophy and poor glycaemic control were the major risk factors for overt nephropathy among Nigerian diabetics. Apreventive strategy should include adequate blood pressure and glycaemic control. PMID- 21977826 TI - The role of echocardiography in the management of patients with congestive heart failure. "Tanzanian experience". AB - OBJECTIVES: To evaluate the usefulness of echocardiography in managing patients with congestive heart failure (CHF) and identify risks of mortality and heart failure re-admissions during follow up. DESIGN: A descriptive prospective hospital based study. SETTING: Muhimbili National Hospital and Hindul Mandal Hospital in Dares Salaam, Tanzania. SUBJECTS: 360 patients (198 male and 162 female) admitted due to congestive heart failure had echocardiography done. MAIN OUTCOME MEASURES: Identifying and characterizing echocardiographic features specific for evaluating patients with congestive heart failure. The patients were followed up for at leas one year. RESULTS: 122 patients had normal left ventricular ejection fraction (LVEF) and 238 patients had reduced left ventricular fraction. Patients with normal LVEF tended to be older and female and were more likely to have a history of hypertension whereas patients with reduced LVEF had a longer history of heart failure due to dilated cardiomyopathy or valvular heart disease. Seventy nine patients (21.9%) died. Patients with depressed ejection fraction had a higher death rate during follow up as compared with preserved ejection fraction. CONCLUSION: We had demonstrated that echocardiography is a useful non-invasive tool for assessing patients with CHF due to systolic or diastolic dysfunction. PMID- 21977827 TI - Osteosarcoma of the jaws: a 23 year retrospective review. AB - OBJECTIVE: To review 31 cases of osteosarcoma of the jaws in Zimbabwe, and to retrospectively study the age, gender, site distribution, clinical features and treatment outcome ofjaw osteosarcoma in Zimbabwe. DESIGN: Descriptive. SETTING: Oral and Maxillofacial surgical clinics at two specialist referral hospitals, Harare Central Hospital and Parirenyatwa Government Hospital, Harare, Zimbabwe. SUBJECTS: 31 cases ofosteosarcoma of the jaws. METHOD: Clinical records of patients who presented with osteosarcoma of the jaws during the period January 1981 to December 2003 were reviewed for age, gender, site of lesion, radiology, histopathology, treatment outcome and follow up. RESULTS: There were 31 cases of jaw osteosarcoma during the 23 year period: 45.2% (n=14) males and 54.8% (n=17) females, mean age 27 years. Of the cases 83.9% occurred in the mandible and 16.1% in the maxilla. Surgery was the treatment of choice. The majority of patients were lost to follow up within 12 months. CONCLUSION: Jaw osteosarcoma is most common in the mandible with an equal male and female affliction in a relatively young age group. PMID- 21977828 TI - Salivary gland tumour of the lip: report of two cases and literature review. AB - BACKGROUND: Salivary gland tumours (SGT'S) are uncommon. The minor glands are dispersed throughout the upper aerodigestive submucosa including the lip. OBJECTIVE: To present two case reports of salivary gland tumour of the upper lip and highlight its diagnostic and therapeutic challenges. CASE REPORTS: A 50-year old female farmer presented with a two year history of swelling of the upper lip and the histology revealed a pleomorphic adenoma of the minor salivary gland. She was offered a wide excision which resulted in a huge upper lip defect managed by a two staged lip switch ABBE flap. The second patient, a 40-year-old female teacher presented with a 10 year history of a left sided upper lip swelling. Histology revealed pleomorphic adenoma. She was offered an excision with no evidence of recurrence after 26 months of follow up. CONCLUSION: Salivary gland tumours should be considered as a differential diagnosis of tumours of the lip: Early presentation is advocated as late presentation with advanced tumour presents diagnostic and therapeutic challenges. PMID- 21977829 TI - Impact of HIV and AIDS on the eldery: a case study of Chiladzulu district. AB - HIV may affect the elderly in a number of ways. They may become infected themselves; their children may suffer prolonged illness and incapacity, and need the elderly to look after them; the same children may then die from the illness, leaving the elderly without the support of the next generation; this bereavement also leaves the older people to meet funeral costs and then to take care of orphans left behind. HIV has impacts on old people in ways that are social, economic, psychological and physical in nature. AIMS: We wanted to understand the socio-economic impacts of HIV/ AIDS on lives of older people following the death of their productive children, and to examine how the elderly struggle to take care of HIV/AIDS orphans. While it is generally appreciated that older people undergo such hardships, little research has been done in Malawi to unravel the magnitude of thes problems. We hope that our findings will increase awareness and lead to more being done to alleviate the problems faced by older people as a result of HIV/AIDS. RESULTS: The results reveal that older people have no alternative but to provide care and support to their ill children, and following the death of their children to become parents again in taking care of the orphaned grandchildren. This is a particularly big challenge in a country like Malawi, dependent on hand-hoeing for subsistence agriculture, where food production requires people who are physically strong. 79% of older people taking care of HIV/AIDS patients or orphans were found to have limited or no information about HIV/AIDS. 31% were dependent on relatives for support, while 69% sustained themselves through piece work, small business or farming. CONCLUSION: Elderly people need more resources and assistance to enable them to fulfil their vital role in caring for HIV-AIDS orphans. They are also in critical need of more information about HIV-AIDS, as many are sexually active with multiple partners, and preventive information is currently not reaching this important section of the community. PMID- 21977830 TI - Service providers' perception of the quality of emergency obsteric care provided and factors indentified which affect the provision of quality care. AB - AIM: The aim of the study was to investigate health workers' perception of the quality of, and factors which impact provision of quality emergency obstetric care. METHODS: This exploratory, descriptive qualitative study was conducted at Mwanza district hospital in Malawi. Qualitative data was obtained through 14 individual in-depth interviews with the health workers involved in the management of women who experienced major obstetric complications. RESULTS: The health workers' overall perception of the quality of emergency obstetric care provided was poor. The poor quality of care was identified as related to client related factors and facility/staff factors. Client factors which emerged as contributing to poor quality care were; the client delay in seeking care: reliance on TBAs, reliance on traditional medications, and lack of awareness regarding signs of an obstetric emergency. Facility/ staff themes which emerged as contributing to the poor care were; inadequate resources, inadequate staffing, poor teamwork, and inadequate knowledge/supervision. CONCLUSION: The findings of this study reveal that health care workers rate the quality of emergency obstetric care they provide as poor. They were able to identify structure and process factors which contribute to this overall poor quality emergency obstetric care provided. These were attributed to health care system problems and client problems. Only through addressing the contributing factors will true improvement of management of obstetric emergencies occur. PMID- 21977831 TI - MaiMwana women's groups: a community mobilisation intervention to improve mother and child health and reduce mortality in rural Malawi. AB - This article presents a detailed description of a community mobilization intervention involving women's groups in Mchinji District, Malawi. The intervention was implemented between 2005 and 2010. The intervention aims to build the capacities of communities to take control of the mother and child health issues that affect them. To achieve this it comprises trained local female facilitators establishing groups and using a manual, participatory rural appraisal tools and picture cards to guide them through a community action cycle to identify and implement solutions to mother and child health problems. Significant resource inputs include salaries for facilitators and supervisors, and training, equipment and materials to support their work with groups. It is hypothesized that the groups will catalyse community collective action to address mother and child health issues and improve the health and reduce the mortality of mothers and children. Their impact, implementation and cost-effectiveness have been rigorously evaluated through a randomized controlled trial design. The results of these evaluations will be reported in 2011. PMID- 21977832 TI - Paediatric wandering spleens in Malawi. PMID- 21977833 TI - Locally advanced skin cancer in an albino: a treatment dilemma. PMID- 21977834 TI - Upper gastrointestinal endoscopy in Malawi: an opportunity. PMID- 21977835 TI - Examining the urine--what can it tell us at the bed-side? AB - Urine is a window to understanding diseases of the kidney and systemic disorders. It is the easiest bodily fluid to obtain can be analysed in resource limited settings where it is of great value in enhancing diagnostic and therapeutic pathways. Asking questions about urine and urination in each clinical history and routinely analysing the urine at the bed-side are that all health professionals should have and, equally importantly, should use. PMID- 21977836 TI - Opinions on the improvement of the health system in the country: Is the government suceeding in improving the health system in the country? PMID- 21977837 TI - "We are trying hard to equip students with necessary skills so that they easily manage the clinical conditions in the country". PMID- 21977838 TI - Mandatory HIV testing? A public debate. Report of an open panel discussion convened in Blantyre, December 2010. PMID- 21977839 TI - HIV status disclosure among people living with HIV/AIDS at FASO, Mutare, Zimbabwe. AB - OBJECTIVE: To examine the prevalence, patterns and reasons for disclosure of HIV status among people living with HIV/AIDS. DESIGN: Adescriptive cross sectional survey. SETTING: FamilyAIDS Support Organisation (FASO), Mutare, Zimbabwe. SUBJECTS: A random selection of members of FASO attending clinic or meetings. OUTCOME MEASURES: Disclosure of HIV seropositivity to sexual partner, to one or more family members, to health care workers and to the wider public. RESULTS: There was 79%, 72% and 70% disclosure to the family, health workers and to sexual partners respectively. While public disclosure was 23%, more people wanted to disclose but did not get an opportunity. Main reasons for disclosure to family were to obtain psychosocial and material support; to the public it was to give HIV/AIDS a face; and to the sexual partner it was to have safer sex. Knowing one's HIV status for a year or longer was significantly associated with disclosure to family, sexual partner and the public. Females were significantly more likely to disclose to family members compared to males (p=0.004). People in abusive relationships were significantly less likely to disclose to sexual partners (OR=0.17, p=0.039). CONCLUSION: Though disclosure rates were generally high, attention must be given to the small number of people engaging in high-risk behaviour, and disclosure counseling needs to be enhanced. Domestic violence hindered disclosure and we advise that it must be prevented. PMID- 21977840 TI - Incidence of neonatal morbidity at Gondar town, Ethiopia. AB - OBJECTIVE: To determine the incidence and pattern ofneonatal morbidity. DESIGN: For all neonates delivered in the hospital at least one home visit was arranged to collect morbidity data during neonatal period. This collection took place for a period of one year from 1 September 1995 to 31 August 1996. SETTING: Maternity Ward of the Gondar College of Medical Sciences Hospital. PATIENTS: 320 neonates were visited at home and were evaluated for any morbidity. RESULTS: Of the 320 neonates visited at home during the first 24 to 38 days post delivery 83 (25.9%) were found to be sick. URTI (Upper Respiratory Tract Infection), jaundice, pneumonia and neonatal septicimia were diagnosed by physical examination. Non breastfeeding was associated with neonatal morbidity (p<0.001). CONCLUSIONS: The neonatal morbidity found during the home visit in this study is very high. A concerted effort is needed to improve both antenatal and postnatal care services to prevent neonatal morbidity and to identify sick neonates timely to provide appropriate care in this setting. PMID- 21977841 TI - Pattern of cleft lip and palate in Dar-es-Salaam. AB - OBJECTIVES: To analyse the pattern of cleft lip and palate patients managed at two hospitals in Dar-es-Salaam. DESIGN: A retrospective descriptive study. SETTING: Muhimbili National Hospital and Comprehensive Community Based Rehabilitation Tanzania Disability Hospital which are special referral centres where most of the cleft lip and palate patients in Dar-es-Salaam are managed. SUBJECTS: Two hundred and sixty nine patients were seen during the study period form January 2005 to December 2006. RESULTS: A total of 269 patients with oral facial clefts were seen during the two year period. Cleft lip combined with cleft palate was the commonest cleft disorder accounting for 44.5% of cases followed by isolated cleft lip (38.3%) and cleft palate only (16.3%). Male patients predominated for unilateral clefts and there was a slight preponderance of 1.7:1. The majority of patients presented at an age of less than five years (60.2%) with an average age of nine months. Late presentation is still common and mainly attributed to ignorance, lack of access to health care facilities and financial constraints. CONCLUSION: The pattern of oral-facial clefts does not differ much from other parts of Africa and emphasis should be made to increase public awareness and improve health care facilities to manage these patients effectively. PMID- 21977842 TI - The prices people pay for medicines in Zimbabwe. AB - OBJECTIVES: To collect, analyse and compare prices of medicines in different sectors and parts of the country and to compare them with the medicine prices in other countries. DESIGN: A prospective cross sectional study. SETTING: Pharmacy outlets in Zimbabwe comprising 27 retail pharmacies, 23 dispensing doctors, eight public hospital pharmacies and seven municipal clinics. MAIN OUTCOME MEASURES: Median price ratios, 25th percentiles and 75th percentiles. RESULTS: Innovator brands in the private sector were priced 10 times the International References Prices (IRP) and more than three times the price of generic medicines. Dispensing doctors were charging the highest prices for medicines and the public sector had the least prices. The national procurement agency, NatPharm, procured medicines at prices slightly below the Management Sciences for Health (MSH) prices. Prices of medicines in the public sector were higher than average prices for medicines from seven other African countries. CONCLUSION: Medicine prices in Zimbabwe are high, a scenario that may compromise affordability and accessibility to medicines especially by the poor. Urgent steps are needed to reduce the level and effect of the high prices on the population, especially the poor. PMID- 21977843 TI - Medications for chronic pain practical review. AB - This review is confined to the drug management of chronic pain, and is specifically adapted to the resource-poor environment and the HIV pandemic of sub Saharan Africa. A brief classification of chronic pain is followed by a discussion of the different classes of medications in use, including those used in migraine. An approach to the rational drug management of neuropathic pain is presented. In conclusion some general principles for prescribing in this setting are derived. PMID- 21977844 TI - Behavioural factors associated with cutaneous anthrax in Musadzi area of Gokwe North, Zimbabwe. AB - OBJECTIVES: To determine behaviour factors for contracting human cutaneous anthrax among residents of Musadzi area. DESIGN: We conducted a matched case control study for age, sex, and village. SETTING: A rural community in Musadzi area of Gokwe North district. SUBJECTS: We interviewed 35 cases and 35 controls. A case was defined as any resident/visitor of Musadzi, diagnosed with anthrax between 9 September and 10 November 2004. A control was any resident who had not been diagnosed with anthrax and had no lesions suggestive ofanthrax on day of the interview. MAIN OUTCOME MEASURES: Behaviour factors associated with contracting anthrax. RESULTS: In September 2004, cattle were reported to be dying in Musadzi area. Bacillus anthracis was positively identified in a blood smear from some of the carcasses. The attack rate among humans was 5%. Risk factors associated with contracting anthrax were: skinning of animals that had died from unknown causes AOR=3.8 (95% CI:1.3-10.7); preparation of the meat for cooking (AOR=3.1 (95% CI:1.16-8-4); preparation of the meat for drying AOR=2.7 (95% CI: 1.0081-7.4); belonging to a religious or ethnic sect that allow handling of meat from animals that had died from unknown causes (AOR=5.2 (95% CI: 1.8-14.8). CONCLUSION: The human anthrax outbreak was secondary to an anthrax epizootic occurring in cattle. The Ministry of Health activated the local zoonotic committee, carried out anthrax awareness campaigns, supervised the destruction of carcasses, disinfected potentially contaminated sites and introduced a participatory health education tool on anthrax. The veterinary department quarantined and vaccinated cattle. PMID- 21977845 TI - Laryngeal carcinoma: our experience at Obafemi Awolowo University Teaching Hospital complex, Ile-Ife, Nigeria. AB - OBJECTIVES: To determine the prevalent age, frequency, pattern ofpresentation, investigations and outcome of management of laryngeal carcinoma in our environment. DESIGN: 10 year retrospective study (January 1994 to December 2003). SETTING: Teaching hospital. SUBJECTS: 13 patients with tissue diagnosis managed for laryngeal carcinoma. MAIN OUTCOME MEASURES: The age, sex, occupation, presentation, use of cigarettes and alcohol, investigations, tissue diagnosis, outcome of management and duration of follow up were extracted from hospital records and analysed. RESULTS: The age of patients ranged 38 to 88 years (median 69, male: female ratio=12:1). The histopathology was squamous cell carcinoma in all. Common symptoms included hoarseness of voice and breathlessness in all the patients, cough and weight loss in seven patients and otalgia in six. Only one patient indulged in alcohol while two were regular cigarette smokers. All the patients presented in stage IV with respiratory distress necessitating emergency tracheostomy in all. Seven patients had total laryngectomy plus post-operative radiotherapy while two patients had pharyngo-laryngectomy, thyroidectomy and radical neck dissection plus post-operative radiotherapy and thyroxine supplement. Post operative complications included pharyngocutaneous fistula in two patients, pharyngeal stenosis, stoma stenosis, and hypocalcaemia with hypothyroidism in one patient each. The fistulae were management conservatively. Prognosis was good despite late presentation. CONCLUSION: Laryngeal carcinoma occurs predominantly in males. Presentation is late with hoarseness of voice and breathlessness in our community. Soft tissue neck X-ray is a useful diagnostic tool. Scarcity of radiotherapy centres, ignorance, local taboos, poverty and poor recognition by general medical practitioners negatively affected management of the patients. Laryngeal carcinoma should be excluded when managing elderly patients for bronchial asthma. PMID- 21977846 TI - Evaluation of cost per test of clinical biochemistry tests at Parirenyatwa Central Hospital Laboratory, Harare, Zimbabwe. AB - OBJECTIVES: To determine the cost per test for selected clinical biochemistry tests at Parirenyatwa Central Hospital, Harare, Zimbabwe. DESIGN: A retrospective study for the month January 2003. Cost analysis was based on a 'bottom-up' micro cost analysis technique. SETTING: Parirenyatwa Central Hospital Laboratory. RESULTS: There was wide variation between the cost of performing a test and the hospital fee schedule offered in payment. The greatest variation was obtained for low frequency tests and direct consumables accounted for 61.2% ofthe total costs. CONCLUSION: Laboratory tests are heavily subsidized and there is need to contain the escalating costs by adopting some aggressive cost recovery measures. Introduction of systematic teaching of health economics in the colleges of health sciences is also advocated. PMID- 21977847 TI - Open mastoidectomy and temporalis flap in the control of chronic otorrhoea. AB - Open mastoid surgery still remains a principal operative treatment for chronic discharging ear. The indications for this procedure still abound in the tropics although it is rarely done in the developed countries nowadays. This series re emphasize the control of chronic otorrhoea and operative wound infection as benefiting from a combined open mastoidectomy and reconstruction with deep temporalis fascia flap in children. The operative technique is further discussed. It is our hope that repopularising this procedure will help in the control of highly prevalent chronic ear in the tropical environment. PMID- 21977848 TI - Viewpoint: Gentamicin for treatment of gonococcal urethritis in Malawi. PMID- 21977849 TI - Systematic review: epidemiology of oesophageal cancer in Sub-Saharan Africa. AB - BACKGROUND: Currently, oesophageal cancer is not a public health priority disease in Sub-Saharan Africa. AIM: Analysis of published scientific studies regarding oesophageal cancer in Sub-Saharan Africa was done to ascertain the incidence, prevalence and geographical distribution of the disease in the region. METHODS: A pub med literature search was conducted for articles ranging from 1950 to 2009 database involving the following key words: oesophageal carcinoma, incidence, prevalence and sub-Saharan Africa. RESULTS: 54 articles were retrieved, of which 16 were analyzed. Differences in the study methodologies used made the comparison amongst studies difficult. Overall, however, studies show that oesophageal cancer is on the increase in the region with its epicenter in the eastern and southern Africa. Incidence of the disease is higher in males than females and is prominent among 45-64 years age group in both sexes. Squamous cell carcinoma is a cell type more common than adenocarcinoma. CONCLUSION: Oesophageal cancer is on the increase in the Sub-Saharan African Region with uneven geographical distribution. Therefore, countries in the region are encouraged together with global health organizations to include oesophageal cancer amongst diseases of public health importance for effective prevention, early diagnosis and effective treatment. PMID- 21977850 TI - Repositioning family planning through community based distribution agents in Malawi. PMID- 21977851 TI - Establishing a children's orthopaedic hospital for Malawi: an assessment after 5 years. AB - Beit Cure International Hospital (BCIH) is a specialist orthopaedic hospital providing surgical services to the children of Malawi. The hospital started treating patients in late 2002, and this analysis represents an attempt to assess the impact of the hospital, and develop strategies for future partnerships and development. Analysis was made of all the 563 case files of new patients treated operatively in the fifth year of hospital services. Data recorded included district and region of origin of patient, diagnosis, age and sex. Patients were treated from all 3 regions, with almost 50% coming from Southern region. Club foot, burn contracture, and genu varus were the most common diagnoses. Half the children were infants up to 5 years of age, while 60% were male. The underlying reasons behind these findings are analysed and their implications in terms of future hospital strategy are discussed. PMID- 21977853 TI - "I can say that during the past years the college has produced excellent researchers....interview by Thengo Kavinya. PMID- 21977852 TI - Ward round--an acute abdominal emergency. PMID- 21977854 TI - Progress in study on synergism and detoxification of Chinese medicine for glucocorticoid. AB - Glucocorticoid (GC) plays an important role in anti-inflammatory, anti-allergic effects and immunosuppression, and has become a widely used drug in clinical departments. However, GC also produces a number of serious side effects at the same time. After GC acting on human body, the syndrome change has some regular pattern and it can be treated on the basis of syndrome differentiation and stage to aim at further improving therapeutic efficacy. The Chinese medicine can reduce the side effects of GC when treating the primary disease, thus plays a role in Synergism and Detoxification. PMID- 21977855 TI - Clinical study on auricular acupoint penetration needling along the skin for treatment of a variety of pain syndrome and dysfunction. AB - This paper is a summary of clinical studies on auricular acupoint penetration needling along the skin for treatment of pain and dysfunction in recent 10 years. Auricular acupoint penetration needling along the skin was used to observe rapid analgesic effects and clinical efficacy on cervical spondylopathy, periarthritis of shoulder, pain in waist and lower extremities, migraine, and other peripheral neuropathic pain, and stroke sequels, soft tissue injury, and so on. Self-control method was used in the studies at the first stage, and clinically randomized control trial methodwas used for systematic comparison with other therapies at the second stage. Results indicated that the auricular acupoint penetration needling along the skin had obviously clinical effects on cervical spondylopathy, periarthritis of shoulder, pain in waist and lower extremities, migraine, soft tissue injuries and stroke sequels, with a better rapid analgesic effect as compared with ear perpendicular needling method. PMID- 21977856 TI - Effects of liandou qingmai recipe (see text) on endothelin-1, nitric oxide, interleukin-6 and interleukin-10 levels in patients with coronary heart disease. AB - OBJECTIVE: To observe effects of Liandou Qingmai Recipe (see text) on endothelin 1 (ET-1), nitric oxide (NO), interleukin-6 (IL-6) and IL-10 levels in patients with coronary heart disease. METHODS: Total 101 cases with coronary heart disease were randomly divided into a treatment group (n = 45) treated by Liandou Qingmai Recipe and a standard treatment group (control group, n = 56), with a normal group of 16 health persons set up. Changes of ET-1, NO, IL-6 and IL-10 levels were measured before treatment and after treatment for two weeks. And the data were analyzed by SPSS 16.0 statistic software. RESULTS: Before treatment, the levels of ET-1, IL-6 and IL-10 levels were significantly higher and NO was significantly lower in the patients with coronary heart disease than those in the normal group (90.7 +/- 12.7 ng/L vs 41.8 +/- 13.5 ng/L, 9.17 +/- 0.18 ng/L vs 1.10 +/- 0.08 ng/L, 1.94 +/- 0.26 ng/L vs 1.09 +/- 0.06 ng/L, and 92.2 +/- 17.7 micromol/L vs 124.5 +/- 27.2 micromol/L; all P < 0.05), with no significant differences in the levels of ET-1, NO, IL-6 and IL-10 between the treatment group and the control group (P > 0.05); After treatment, ET-1 and IL-6 significantly decreased in the treatment group and the control group, and NO increased in the treatment group; And IL-6 level was significantly lower and NO level was higher in the treatment group than those in the control group (4.48 +/- 1.22 ng/L vs 5.13 +/- 1.85 ng/L, 117.4 +/- 22.3 micromol/L vs 92.4 +/- 17.1 micromol/L; both P < 0.05); There was a positive correlation between IL-6 and IL-10, and a negative correlation between NO and IL-10 (r = 0.142, r = -0.152; both P < 0.05). CONCLUSION: Liandou Qingmai Recipe can decline IL-6, IL-10 and ET-1 levels, and raise NO level in patients with coronary heart disease on the basis of standard treatment, so as to inhibit endothelial inflammatory response, improve vascular endothelial function, with stronger anti-AS action; And vascular endothelial lesion is related with inflammatory response. PMID- 21977857 TI - Clinical research on comprehensive treatment of senile vascular dementia. AB - OBJECTIVE: To observe the curative effect of combined Chinese medicine, acupuncture and rehabilitation therapy on vascular dementia (VD), and to compare the Western medicine piracetam. METHODS: Total 134 VD patients screened in reference to the standard for VD diagnosis in DSM-IV were randomly divided into a Chinese medicine plus rehabilitation group (32 cases), a Chinese medicine plus acupuncture group (33 cases), a Chinese medicine and acupuncture plus rehabilitation group (37 cases) and a Western medicine piracetam group (32 cases). Mini Mental State Examination (MMSE) and Bless Behavior Scale (BBS) were used to assess changes in intelligence disorder before treatment and after 12 week treatment. RESULTS: BBS score, living ability and daily habit were enhanced after treatment in all groups. Cognitive function and behavioral ability were improved with similar total curative effects in all the 4 groups. Directional ability and short-term memory ability were significantly enhanced after treatment (P < 0.05) in both the Chinese medicine plus rehabilitation group and the Chinese medicine plus acupuncture group groups. Living ability was significantly improved after treatment in the Chinese medicine and acupuncture plus rehabilitation group (P < 0.01). However, no obvious difference was shown before and after treatment in the piracetam group. CONCLUSION: The improvement of living ability in the comprehensive treatment group is better than that in the other groups. Chinese medicine and acupuncture plus rehabilitation treatment can improve intelligence and living ability of senile VD patients. PMID- 21977858 TI - Analysis of clinical syndromes in 47 patients with pancreatic cancer at late stage. AB - OBJECTIVE: To analyze the law governing the distribution of traditional Chinese medicine (TCM) syndromes of pancreatic cancer. METHODS: The authors used retrospective study to statistically analyze TCM syndromes of patients, separated complex syndromes and calculated the frequency of appearance of single syndromes. RESULTS: The patients mainly suffered from 4 syndromes: blood stasis syndrome, qi stagnation syndrome, qi (yang) deficiency syndrome, and phlegm dampness syndrome. The distribution of syndromes is rarely related to sex, age and morbid site of patients. CONCLUSION: Owing to complicated distribution of its syndromes, pancreatic cancer should be diagnosed and treated according to its characteristics of deficiency in origin and excess in superficiality. PMID- 21977859 TI - Effects of the modified linggui zhugan decoction (see text) combined with short term very low calorie diets on glycemic control in newly diagnosed type 2 diabetics. AB - OBJECTIVE: To evaluate the effects of the modified Linggui Zhugan Decoction (see text) combined with short-term very low calorie diets (VLCDs) on glycemic control in newly diagnosed type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 20 subjects with newly diagnosed T2DM were treated with the modified Linggui Zhugan Decoction (one-month administration) combined with short-term VLCDs (5 days), and 3-months follow-up. A standard 75-g oral-glucose-tolerance test (OGTT) indexes fasting plasma glucose (FPG), post-prandial 0.5 h and 2 h plasma glucose (P0.5hPG, P2hPG), glycated hemoglobin A(1c) (GHbA(1c)), body weight, body mass index (BMI), insulin function, insulin resistance index, incidence of hypoglycemia, and the liver and renal functions were evaluated before and after treatment. Correlations of BMI with insulin function and insulin resistance were also assessed. RESULTS: After the treatment, the patients' plasma glucose decreased steadily, FPG decreased from 5.8 +/- 0.9 mmol/L at pre-treatment to 5.0 +/- 0.6 mmol/L at 3-months follow-up (P < 0.05), and P2hPG decreased from 11.7 +/ 3.8 mmol/L at pre-treatment to 6.9 +/- 0.9 mmol/L at 3-months follow-up (P < 0.01). The level of GHbA(1c) declined from (6.47 +/- 1.24)% at pre-treatment to (6.14 +/- 0.99)% at 3-months follow-up (P < 0.01). Body weight and BMI also declined significantly. Insulin resistance index was improved obviously and no event of hypoglycemia occurred. Part of the patients companied with fatty liver had a transient increase in hepatic transaminase during the treatment, but it turned to normal after the treatment. CONCLUSIONS: The modified Linggui Zhugan Decoction combined with short-term VLCDs can be safely implemented for steady glycemic control in newly diagnosed T2DM patients. PMID- 21977860 TI - Clinical research on zishengukang pill (see text) used to treat delayed union of fracture. AB - OBJECTIVE: To observe the curative effect of Zishengukang Pill (see text) on delayed union of fracture. METHODS: Sixty-four patients with delayed union of fracture were randomly divided into a control group of 32 cases treated with Western medicine and a treatment group of 32 cases treated with Western medicine and Zishengukang Pill. After 3 courses of treatment with 30 days as a course, the curative effects in the two groups were evaluated and their clinical symptoms, union rate and union time of fracture were compared. RESULTS: The treatment resulted in cure in 25 cases, improvement in 6 cases and ineffectiveness in 1 case with the effective rate at 96.8% in the treatment group, higher than 81.3% in the control group (P < 0.05). The union rate of fracture in the treatment group was higher than that in the control group (34.3% vs. 12.5%, P < 0.05). The union time of fracture in the treatment group was shorter than that in the control group ((4.0 +/- 1.7) months vs. (5.0 +/- 1.4) months, P < 0.05). CONCLUSION: Zishengukang Pill with obvious curative effect in the treatment of delayed union of fracture is worth popularizing. PMID- 21977861 TI - Clinical observations on therapeutic effects of the modified shengjing zhongzi tang (see text) in patients with asthenospermia and oligozoospermia. AB - OBJECTIVE: To compare the therapeutic effects of Shengjing Zhongzi Tang ((see text) Decoction for Generating Sperms) and Wuzi Yanzong Wan ((see text) Pills for Reproduction) for asthenospermia and oligozoospermia. METHODS: Seventy patients with asthenospermia and oligozoospermia were divided into a treatment group of 35 cases treated with Shengjing Zhongzi Tang and a control group of 35 cases treated with Wuzi Yanzong Wan for 3 months respectively. The therapeutic effects were evaluated, the semen parameters were analyzed and the spermatic morphology was judged before and after treatment. RESULTS: In the treatment group, the total effective rate was 91.4% with a pregnant rate of 8.6% spouses, and the markedly effective rate was 65.7%. In the control group, the total effective rate was 85.7% with a pregnant rate of 5.7% spouses, and the markedly effective rate was 54.3%. Both the total effective rate and the markedly effective rate were higher in the treatment group than those in the control group, but with no significant statistical difference (P > 0.05). The spermatic density, spermatic motility and the percentage of normal spermatic morphology were obviously enhanced in the two groups with the indexes in the treatment group superior to those in the control group (P < 0.05 or P < 0.01). CONCLUSION: Shengjing Zhongzi Tang with obvious therapeutic effects for asthenospermia and oligozoospermia can significantly enhance the spermatic density and motility, and raise the pregnant rate in spouses. PMID- 21977862 TI - A study on the correlativity of MRI signal classifications with TCM syndromes in femoral head necrosis patients. AB - OBJECTIVE: To probe into the relation between magnetic resonance imaging (MRI) signal classifications and TCM syndromes in femoral head necrosis patients, so as to provide reference for TCM diagnosis of this disease. METHODS: Refering to the criteria for TCM syndrome types of necrosis of the femoral head described in "The Guiding Principles of Clinical Studies of New Chinese Drugs" and Shimizu and Mitchell's MRI signal classifications, MRI signal classifications between different TCM syndrome types were compared. RESULTS: The Shimizu signal classification of different TCM syndrome types had statistically significant difference (P = 0.04); Both T2WI+fs and Mitchell signal classifications of different TCM syndrome types had no statistical by significant differences (P = 0.42 or P = 0.15). CONCLUSION: There is a certain correlativity of TCM syndrome types of necrosis of the femoral head with T1WI signal classification of MRI. MRI signal classification may contribute to objectivity in TCM syndrome typing of this disease. PMID- 21977863 TI - Clinical research of acupuncture on malignant tumor patients for improving depression and sleep quality. AB - OBJECTIVE: To study the effect of acupuncture on depression and insomnia of malignant tumor patients. METHODS: Eighty cases of cancer related depression and sleep disorders were randomly divided into 2 groups: treatment 1 group (acupuncture n = 40) and control group (Fluoxetione n = 40). All patients were assessed by Self-rating Depression Scale (SDS), Hemilton Depression Rating Scale (HAMD) and Pittsburgh Sleep Quality Index (PSQI) after treatment for 30 days. RESULTS: Before treatment the SDS and HAMD scores of the trial group were 64.12 +/- 5.34 and 20.92 +/- 2.38, those of the control group were 64.24 +/- 4.98 and 20.72 +/- 2.74, after treatment the SDS and HAMD scores of the trial group were 43.64 +/- 5.28 and 9.88 +/- 1.27 respectively, significantly lower than those of the control group (50.76 +/- 5.42 and 13.72 +/- 2.05 respectively, both P < 0.05). Before treatment the PSQI score of the trial group and the control group were 14.48 +/- 1.71 and 13.92 +/- 2.59, after treatment the PSQI score of the trial group was 7.92 +/- 1.22 after treatment, significantly lower than those of the control group (11.44 +/- 1.89, P < 0.01). CONCLUSION: Acupuncture can effectively reduce malignant-related depression, improve sleep quality, and help to improve the quality of life of cancer patients. PMID- 21977864 TI - Effects of panax notoginseng saponins on homing of C-kit+ bone mesenchymal stem cells to the infarction heart in rats. AB - OBJECTIVE: To investigate the effects of panax notoginseng saponins (PNS) on homing of C-kit+ bone mesenchymal stem cells (BMSCs) to the infarction heart. METHODS: The acute myocardial infraction (AMI) model was established in 140 Wistar rats, 105 model rats survived after operation, and the model rats were randomly divided into five groups, 21 rats in each group: Western medicine group mobilized by subcutaneous injection of human granuloctye colony stimulating factor (G-CSF) 50 microg x kg(-1) x d(-1); sham operation group and a model group treated by subcutaneous injection of normal saline 50 microg x kg(-1) x d(-1); Chinese medicine group mobilized by intraperitoneal injection of Xuesaitong (see text) (ingredients of PNS) 150 mg x kg(-1) x d(-1); integrative medicine group mobilized by subcutaneous injection of G-CSF 50 microg x kg(-1) x d(-1) and intraperitoneal injection of Xuesaitong 150 mg x kg(-1) x d(-1). Except for the sham-operated group, each group was divided into three sub-groups by three time points of 1 d, 7 d and 14 d. G-CSF was injected once a day for 7 d. Xuesaitong was injected once a day until the rats were killed. The flow cytometry was used for detection of C-kit+ cells in the peripheral blood in different time points, and immunohistochemical method was used for detection of the changes of C-kit+ cell and Ki-67+ cell numbers in the marginal zone of AMI. RESULTS: Twenty-four hours after the operation, C-kit+ cells had a slight increase in the model group compared with the sham operation group (P > 0.05). The peripheral blood C-kit+ cells in the integrative group increased significantly compared with the other groups on 7 d and 14 d (all P < 0.05). Meanwhile the expression of C-kit+ cells and Ki-67+ cells in the marginal zone of AMI in the integrative group increased significantly compared with the Chinese medicine group, the western medicine group and the model group on 1 d, 7 d and 14 d (all P < 0.05), and the cells in the integrative group decreased significantly on 14 d compared with that on 7 d (P < 0.05). CONCLUSION: PNS can cooperate with G-CSF to mobilize C-kit+ BMSCs from the marrow into the peripheral blood and promote them "homing" to the infarction heart. PMID- 21977865 TI - Effects of yinchenhao decoction (see text) for non-alcoholic steatohepatitis in rats and study of the mechanism. AB - OBJECTIVE: To observe the effects of Yinchenhao Decoction (see text) for non alcoholic steatohepatitis (NASH) in rats and study the mechanism. METHODS: Total 18 male SD rats were randomly divided into a normal control group, a model group and a treatment group, 6 rats in each group. Rats in the model and treatment groups were fed with high-fat forage for 10 weeks to prepare the NASH model, and the rats in the treatment group were administrated with Yinchenhao Decoction from the 6th week for 5 weeks. All rats were sacrificed at the end of the 10th week and the samples were collected. Serum alanine aminotransferase (ALT) activity, tumor necrosis factor-alpha (TNF-alpha) level, and hepatic triglyceride (TG) and free fatty acid (FFA) contents were determined. Hepatic pathological changes were detected by HE staining. RESULTS: Serum ALT activity, TNF-alpha level, hepatic TG and FFA contents, and the fatty deposition in hepatocytes were significantly reduced in the rats of the treatment group. CONCLUSION: Yinchenhao Decoction has good therapeutic effects for NASH, protecting the liver function and reducing the fatty deposition in liver, which are possibly related with reduction of FFA content and inhibition of TNF-alpha expression. PMID- 21977866 TI - Effects of Chinese herbal medicine serum on the apoptosis of sinoatrial node cells induced by simulated ischemia-reperfusion. AB - OBJECTIVE: To study the effect of Chinese herbal medicine Kangxin Fumai Granule ((see text) Granule for heart diseases) serum on the primary cultured sinoatrial node (SAN) cell apoptosis induced by simulated ischemia-reperfusion (IR). METHODS: The SAN cells removed from SAN tissue of neonatal Wistar rats were cultured and purified with differential attachment and 5'-bromodeoxyuridine (BrdU) treatment. Simulated IR model was adopted. The obtained cells were morphologically observed with inverted microscopy. By using the method of serum pharmacology, the cell apoptosis was measured with TUNEL staining qualitatively and with flow cytometry quantitatively. RESULTS: Three kinds of cells were observed in the cultured SAN cells: spindle, triangle and irregular. The spindle cells comprised the greatest proportion. The SAN cells in the model group showed moderate positive brown staining in the nucleus, and the apoptosis rate increased significantly compared to that in the control group (P < 0.01). While the SAN cells in the Kangxin Fumai Granule high-dose group did not demonstrated positive staining in the nucleus, and the apoptosis rate decreased significantly compared to that in the model group (P < 0.05). CONCLUSION: Of the cells cultured from SAN, the spindle cells were pacemaker cells of SAN in rats. Blockade and/or inhibition of the SAN cell apoptosis might be one of the important mechanisms of Kangxin Fumai Granule in preventing and treating sinoatrial injury induced by simulated IR. PMID- 21977867 TI - Effects of tongmai huoxue yin (see text) on tumor necrosis factor-alpha in the acute cerebral ischemia model rat. AB - OBJECTIVE: To observe the interfering action of Tongmai Huoxue Yin (see text) on the acute cerebral ischemia model rat. METHODS: Total 60 SD rats, 30 females and 30 males, were randomly divided into 4 groups, sham-operation group, model group, Nimodipine group and Tongmai Huoxue Yin group, 15 rats in each group. The acute cerebral ischemia rat model was duplicated, the middle cerebral artery (MCA) were ligated and the thread was inserted for the rats in the model group, Nimodipine group and Tongmai Huoxue Yin group, for the rats in the sham-operation group, the arteries were separated without ligature and the thread was not inserted. After the modeling has succeed, the water-decocted concentrated solution of 20-fold Tongmai Huoxue Yin clinical dosage was intragastrically administrated in a dose of 3 mL/100 g d divided into twice, 1.5 mL/100 g once. Distilled water 3 mL/100 g x d was intragastrically administrated, 1.5 mL/100 g once, for the rat in the model group, Nimodipne suspension 3 mL/100 g x d (0.6 mg / 100 g) for the Nimodipine group and 3 mL/100 g x d (5.4 g/100 g) for the Tongmai Huoxue Yin group, no drugs for the sham-operation group. And changes of tumor necrosis factor-alpha (TNF-alpha) contents in the serum and brain tissue were investigated. RESULTS: Compared with the model group, compared with the sham operation group, serum TNF-alpha content at 5 h of focal cerebral ischemic ischemia in the model group started to increase and reached to the high peak at 12 h, but in both the Tongmai Huoxue Yin group and the Nimodipine group decreased in varying degrees at the same time; compared with the sham-operation group, brain TNF-alpha content at 6 h of focal cerebral ischemic ischemia in the model group started to increase and reached to the high peak at 12 h, but in both the Tongmai Huoxue Yin group and the Nimodipine group decreased in varying degrees, with the most obviously decreased at 24 h of ischemia.Tongmai Huoxue Yin could significantly decrease TNF-alpha content in the brain tissue. CONCLUSION: Tongmai Huoxue Yin has a protective action on acute cerebral ischemia injury in the rat. PMID- 21977868 TI - Effect of zibu shenjing fang (see text) on growth and development of the mouse with kidney-essence insufficiency and study on the mechanism. AB - OBJECTIVE: To investigate effects of Zibu Shenjing Fang (see text) on growth and development of the mouse with insufficiency ofkidney-essence and the mechanism. METHODS: Total 50 mice were randomly divided into a normal group, a model group, a Jingui Shenqi Wan (see text) group, a Zibu Shenjing Fang high dose group and a Zibu Shenjing Fang low dose group, 10 mice in each group. The kidney-essence insufficiency mouse model was established by use of threat-injuring the kidney combined with over-fatigue. At the same time of modeling, the mice in the model group were intragastrically administrated with saline 20 mL x kg(-1) x d(-1), in the Jingui Shenqi Wan group with suspension of the Jingui Shenqi Wan 2.7 g x kg( 1) x d(-1), in the Zibu Shenjing Fang high dose group with Zibu Shenjing Fang 20 g x kg(-1) x d(-1) and in the Zibu Shenjing Fang low dose group with Zibu Shenjing Fang 10 g x kg(-1) x d(-1), for 21 consecutive days. The general state was observed, the body weight was weighted, and serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) contents were detected. RESULTS: Compared with model group, Zibu Shenjing Fang groups and Jingui Shenqi Wan group could improve manifestation of the mouse with kidney-essence insufficiency, increase body weight of the mouse and serum GH and IGF-1 contents, especially in the high dose group. CONCLUSION: Zibu Shenjing Fang gives play to the function of tonifying the kidney and replenishing essence through regulating GH and IGF-1 levels, so as to influence growth and development of the mouse. PMID- 21977869 TI - Effects of polysaccharides extracted from zhu zi shen (rhizoma panacis majoris) on oxidative stress and hemodynamics in rats with adriamycin-induced chronic heart failure. AB - OBJECTIVE: To probe into the intervening action of polysaccharides of Zhu Zi Shen (Rhizoma Panacis Majoris) (PZZS) on oxidative stress and hemodynamics in rats with adriamycin-induced chronic congestive heart failure (CHF). METHODS: After SD rats were successfully modeled with adriamycin, they were randomly divided into a normal control group, a model group, a PZZS group, and a captopril group, and were administrated respectively. At the end of experiment, the hemodynamic function, whole heart weight index, and the blood CK, SOD, MDA, NO, NOS were detected; and the myocardial morphological examinations were carried out. RESULTS: Compared with the normal control group, the arterial systolic pressure (SBP), diastolic pressure (DBP), mean arterial pressure (MAP), heart rate (HR), left ventricular systolic peak (LVSP), and left ventricular pressure change rate (dp/dt(max)) significantly decreased, and left ventricular end diastolic pressure (LVEDP), whole heart weight index, the blood CK, MDA, NO, NOS significantly increased in the model group. PZZS significantly improved the hemodynamic function, lowered the MDA and NO levels, and decreased the CK and NOS activities in the CHF rats. CONCLUSION: PZZS can improve the hemodynamic function, and alleviate the oxidative stress reaction in the CHF rat. PMID- 21977870 TI - Preliminary study on the mechanism of acupoint injection of bone marrow mesenchymal stem cells in improving blood flow in the rat of hind limb ischemia. AB - OBJECTIVE: To explore the mechanism of acupoint injection of bone marrow mesenchymal stem cells (BM-MSCs) in improving blood flow in the rat with hind limb ischemia. METHODS: Twenty-four SD rats were randomly divided into 4 groups: normal control group (n = 6), model group (n = 6), BM-MSCs acupoint injection group (AI group, n = 6) and BM-MSC intramuscular injection group (MI group, n = 6). Sanyinjiao (SP 6), Housanli (ST 36), Zhaohai (KI 6), Huantiao (GB 30) and Yanglingquan (GB 34) were selected for the AI group, and five non-acupoints were selected on gastrocnemius and adductor of ischemic hind limbs in the MI group. BM MSCs were injected to the latter two groups. The rat hind limb ischemia model was established with the method of blocking the femoral artery and its branches. Three weeks after injection of BM-MSCs, in each group, hindlimb adductor and gastrocnemius were taken from the ischemic side. Expressions of vascular endothelial growth factor (VEGF) and transfer growth factor-beta1 (TGF-beta1) in the skeletal muscle were determined with immunohistochemical method, and the small arteries in the skeletal muscle were labeled with alpha-SMA immunohistochemical staining method, the density of small arteries (number of arterioles/number of muscle fibers) and the number of the blood vessel with VEGF positive expression were calculated. The serum levels of VEGF and nitric oxide (NO) were detected. RESULTS: Compared with the model group, the expression of VEGF and TGF-beta1, and the density of small arteries and the number of VEGF positive blood vessels in the AI group and the MI group significantly increased (both P < 0.01). Compared with the MI group, the density of small arteries and the number of VEGF-positive blood vessels in the AI group significantly increased (both P < 0.01); Compared with the model group and the normal control group, the serum expression quantity of NO and VEGF in the AI group and the MI group were significantly increased (P < 0.01). CONCLUSIONS: Acuppoint injection of BM-MSCs secrets more VEGF, TGF-beta1 and NO to increase angiogenesis and arteriogenesis, so as to improve blood flow of the rats of hind limb ischemic. PMID- 21977871 TI - Comparative study of antimicrobial activity and phytochemical analysis of methanolic and aqueous extracts of the fruit of Emblica officinalis against pathogenic bacteria. AB - OBJECTIVE: To investigate antimicrobial potential of aqueous (infusions, decoctions) and methanlic extracts (1:2 and 1:5 concentrations) of Emblica officinalis (amla) against seven pathogenic bacteria namely Staphylococcs aureus, Staphylococcus saprophyticus, Escherichia coli, Enterococcus faecalis, Enterococcus cloacae, Proteus vulgaris and Klebsiella pneumoniae. METHODS: The well diffusion technique was employed. The minimum inhibitory concentration (MIC) was determined using micro-broth dilution methods and phytochemical screening was done as per standard procedures. RESULTS: Aqueous infusion extract of amla exhibited potent antimicrobial activity against E. cloacae followed by E. coli. Preliminary phytochemical analysis of E. officinalis aqueous extracts (infusions and decoctions) only showed presence of tannins, saponins, flavanoids, Terpenoids and phenols. MIC of aqueous extract of E. officinalis was most active against K. pneumoniae. Whereas MIC of methanol extract of E. officinalis shows maximum activity against E. coli. CONCLUSION: Emblica officinalis definitely possesses potent antimicrobial activities and this can serve as an important platform for the development of inexpensive, safe and effective medicines PMID- 21977872 TI - Comparison of the network structural characteristics of calcium signaling pathway in cerebral ischemia after intervention by different components of Chinese medicine. AB - OBJECTIVE: To explore the network control mechanism of the calcium signaling pathway in cerebral ischemic injury after intervention by the main components of Qingkailing (see text), i.e. Baicalin, Jasminoidin and their combination. METHODS: Thirty mice were randomly divided into 5 groups, a baicalin group, a Jasminoidin group, a baicalin plus Jasminoidin group, a nimodipine group, and a model group (n = 6). The global cerebral ischemia-reperfusion mouse model was established. The mice were administrated respectively by injection of baicalin, Jasminoidin, mixture of baicalin and Jasminoidin, and nimodipine into the caudal vein, with the model group given no any drug. Three hours after operation, the brain was removed and sectioned. After calculation of cerebral ischemic area by 2,3,5-triphenyltetrazolium staining, the percentage of infarct volume was calculated. The total RNA of the mouse brain tissue was extracted to obtain the whole genome expression profile, and the differentially expressed genes related to the calcium signaling pathway was analyzed with Bayesian network structures. RESULTS: Compared with the model group, the ischemic area was significantly reduced in the baicalin group, the Jasminoidin group, the Baicalin plus Jasminoidin group (all P < 0.05). The ischemic area in the baicalin plus Jasminoidin group was smaller than the other three groups (all P < 0.01). In the gene regulatory network structures of calcium signaling pathway, the average length and equitability were the highest in the baicalin plus Jasminoidin group, followed by the nimodipine group. CONCLUSION: Compared with a single component, combination of Baicalin and Jasminoidin can more obviously intervene in the overall expression of calcium signaling pathway, and the mechanism is related with the aggregation characteristic of the gene expression network. PMID- 21977874 TI - Getting the straight story... PMID- 21977873 TI - Research on modern nonlinear dynamic model of five-elements theory. AB - This article studied on five elements system and set general and strict model expectations combining with Traditional Chinese Medicine Zang-fu organs theory, in which absolute stable state, conditional stable state or transient stability and instability in mathematical models were corresponding to human healthy state, sub-healthy state (pathological plateau phase) and health deterioration state respectively. Model parameters were set up according to the mutual generation and restriction relations among five elements. The dynamic model of Five-Elements System was built, of which impulse responses were corresponding to human response under TCM treatment. Analyses of initial value and excitation response were conducted by numerical simulation and results turned out to meet the requirements of general model expectation: five elements system dynamic model had self organization function; there existed only one non-global stable point and instability region in the five-dimensional space consisting of variables, in which instability was corresponding to pathological deterioration; system stable region was an unbounded domain and it included the stable sub-regions of special straight line-type, ray-type and line segment-type. Among those ray-types, some contained "Regression Peak" were classed as conditional stable regions while others as absolute ones. The existence of this peak indicates that our body must exceed a "Regression Threshold" when transiting from sub-healthy state (pathological plateau phase) to healthy state through self-regulation mechanism. Impulse excitation can reduce certain threshold and then increase the system health level, which is complied with the operating principle of Five-Elements System and the empirical rule of TCM clinical practice. This model has revealed qualitatively the inherent movement law of Five-Elements System and thus provides a new analysis tool for basic theoretical study on TCM. PMID- 21977875 TI - Patient care and worker compensation cost control. PMID- 21977876 TI - Finding savings on the pharm. PMID- 21977877 TI - Women in transplantation: an interview with Helen Spicer, RN. PMID- 21977878 TI - Using crisis theory to explain the quality of life of organ transplant patients. AB - OBJECTIVES: To evaluate the literature on the stress, coping, and quality of life of organ transplant candidates and recipients, and to place previous research within a theoretical context. DATA SOURCES: CINAHL database, Proquest database, Google Scholar; references from articles were also reviewed to identify additional data. STUDY SELECTION: Qualitative and quantitative research studies and meta-analyses pertinent to the stress, coping, and quality of life of transplant candidates and recipients were selected. RESULTS: Stressors associated with the transplantation process, coping strategies of transplant patients, and quality of life or transplant patients have been well researched for many years. Patients typically use problem-focused coping strategies in response to various stressors. Transplant recipients typically report a higher quality of life than do transplant candidates; however, posttransplant quality of life does not typically equal the quality of life of healthy nonpatients. CONCLUSIONS: The relationship between stress, coping, and quality of life of transplant patients has not yet been systematically investigated from a theoretical perspective. Recommendations for further research are provided. PMID- 21977880 TI - The roles of social support and psychological distress in lung transplant candidacy. AB - CONTEXT: Social support appears to be an important component in lung transplantation. However, the relationship between social support, psychological distress, and listing status has not been evaluated in lung transplant candidates. OBJECTIVE: To evaluate the relationships between depression, anxiety, and social support in patients with end-stage lung disease being evaluated for transplantation and determine (1) relationships between social support, depression, anxiety, and coping via seeking emotional and instrumental support; (2) whether social support explains a significant proportion of the variance in depression and anxiety; and (3) whether these factors were associated with whether a patient was listed for transplant. DESIGN: For this observational study, patients completed self-report questionnaires after their pretransplant evaluations. Listing status was subsequently obtained from medical records. PATIENTS: Participants were patients with end-stage lung disease evaluated for transplantation at a major hospital. MEASURES: Medical Outcomes Study Social Support Survey, COPE Inventory, Beck Depression Inventory, and State-Trait Anxiety Inventory. RESULTS: Social support was associated with depression, anxiety, and seeking support (P values < .01). When other factors related to these variables were controlled for, social support explained a significant proportion of the variance in depression (9%), state anxiety (8%), and trait anxiety (7%; all P values <.001). Patients who were listed for transplant reported seeking more emotional and instrumental support than did patients who were not listed (all P values < or = .05). Whether a patient was listed for transplant was not associated with depression, state anxiety, trait anxiety, or availability of social support. Results highlight the important role that coping via seeking support plays in transplant candidacy. PMID- 21977879 TI - Time-motion analysis of research nurse activities in a lung transplant home monitoring study. AB - BACKGROUND: The emergence and subsequent integration of new technologies precipitate changes in roles and work lives of nurses. The nurses' work with home monitoring technologies within a spirometry-based program that transmits pulmonary function data after lung transplantation has characteristics that are distinct from other types of direct patient care. Nurses' changing roles in such programs after transplantation have not been well described. OBJECTIVE: To describe a time-motion study of 2 research nurses in the context of a home spirometry study to monitor patients' pulmonary status after lung transplantation. METHOD: A detailed list of research nurses' 67 routine work related activities was developed and validated to monitor and record activities of research home monitoring nurses. Two weeks of observations were completed; recordings of a second observer established reliability of observations. RESULTS: In 48.8 hours of observation, 610 tasks related to monitoring of 45 patients were recorded. Task time ranged from brief seconds (eg, data review) to 39 minutes (eg, clinic visits). Between-observer intraclass correlation (r = 0.96) reflected high agreement in observations of the duration of activities. Agreement for category of activity was strong (kappa = 0.82), with high levels of agreement (96%). Computer tasks were the most frequent (118 tasks/week) and most time intensive activities. Nurses' face-to-face interactions with health professionals were equally time intensive (both 267 minutes/week), but not as frequent. Data review tasks were the second most frequent (49/week), although less time intensive (47 minutes/week). CONCLUSION: Findings reveal patterns of effort and time expenditure in nurses' evolving roles in home monitoring of the health status of patients after lung transplantation. These findings highlight the centrality and importance of well-developed data management, computer skills, and interprofessional communication skills of nurses who perform responsibilities in this emerging role in transplantation. Efforts to streamline computerized information access, as through integrated information systems, and methods to enhance efficiency in connecting with patients in the clinic may free up time for nurses to engage in other activities of direct benefit to patients. Strategies to supplement face-to-face meetings among professionals with electronic modalities may reduce the time spent meeting, while maintaining or enhancing communication. PMID- 21977881 TI - Is Model for End-Stage Liver Disease score associated with quality of life after liver transplantation? AB - CONTEXT: The Model for End-Stage Liver Disease (MELD) is used to predict short term mortality of patients on the liver transplant waiting list and to allocate deceased donor livers for transplantation. OBJECTIVE: To examine the relationship between MELD score before transplant and quality of life and other functional status indicators after transplant. DESIGN, SETTING, AND PATIENTS: Two-hundred sixty-five adults from 2 transplant programs completed quality-of-life measures 1 year after transplantation. A subcohort (n = 115) also completed quality-of-life assessments before transplant. Clinical parameters at the time of transplantation were collected from their medical records. MAIN OUTCOME MEASURES: Short Form-36 Health Survey, version 2; Transplant Symptom Frequency Questionnaire. RESULTS: Patients with MELD scores greater than 25 at transplantation had significantly higher scores on the Short Form-36 general health (P = .004) and physical component summary (P = .02) than did patients with MELD scores of 25 or less. However, scores on the Transplant Symptom Frequency Questionnaire did not vary significantly by MELD score. Child-Turcotte-Pugh (CTP) score, a measure of disease severity, was significantly associated with total symptom frequency after transplant (P = .03) but was not correlated with any domains on the Short Form 36. In the subcohort of 115 patients, a MELD score greater than 25 at the time of transplantation was associated with greater improvement in physical functioning (11.3 vs 4.8, P = .02), role functioning-physical (10.7 vs 4.7, P = .04), general health (11.9 vs 5.5, P = .03), vitality (10.4 vs 5.2, P = .02), and physical component summary (12.3 vs 5.4, P = .01) relative to patients with MELD scores of 15 to 25. CONCLUSIONS: The relationship between disease severity before transplant and quality of life after transplant is different depending on the index of disease severity used (MELD vs CTP) and whether the assessment of quality of life is general or specific to transplant-related symptoms. PMID- 21977882 TI - Kidney paired donation 2011. AB - Patients with incompatible live donors have had to resort to the long wait on the deceased donor list. Now, through kidney paired donation, these incompatible pairs can enter a kidney exchange program where kidneys are "swapped" between incompatible pairs. This review highlights the evolution of kidney paired exchange and reviews the challenges and ethical considerations within a paired exchange system. PMID- 21977883 TI - Donor families, distinctive secondary losses, and "second death" experiences. AB - Communication between donor families and the recipients of their loved ones' organs and tissues is a relatively new area of study. The National Kidney Foundation founded the National Donor Family Council in 1992 as a home for donor families. One of several items addressed by the Council was guidelines for communication, supporting the rights of donor families and recipients to communicate and build relationships should they choose to do so. Donation and transplant agencies play a strong role in facilitating and supporting donor families and recipients with these unique new relationships. This article offers 3 case examples of distinctive secondary losses and "second death" experiences encountered by some donor family members when the donation of tissues or organs they have authorized could not be used for transplantation, when those grafts fail or are rejected, or when the recipient dies. On that basis, the article explores the nature of these experiences and some reasons why they occur. Initial recommendations about how to address these experiences are provided. Finally, a 4 part agenda is suggested for research about (1) the nature of these distinctive secondary loss and second death experiences encountered by some donor families; (2) communications between donation and transplant professionals, on the one hand, and potential and actual donor family members, on the other hand; (3) the education, training, and support of professionals who provide bereavement support to donor family members; and (4) a review of the National Communication Guidelines. PMID- 21977884 TI - Advanced assessment of platelet function during adult donor care. AB - Abnormal platelet function may complicate the assessment and treatment of continuing blood loss, hypotension, and coagulation disorders during adult donor care. Antiplatelet drugs, such as aspirin, nonsteroidal anti-inflammatory drugs, clopidogrel (Plavix), ticlopidine (Ticlid), prasugrel (Effient), abciximab (ReoPro), eptifibatide (Integrilin), and tirofiban (Aggrastat) are commonly prescribed for older patients. These medications may be part of home therapy or may be given during acute cardiac or cerebrovascular crises that may lead to brain death and organ donation. This discussion reviews normal platelet formation and function, drug actions, methods to evaluate medication effects, pharmacological characteristics, treatment recommendations for platelet transfusion, and risks attendant with those infusions. PMID- 21977885 TI - Zero risk tolerance costs lives: loss of transplantable organs due to human immunodeficiency virus nucleic acid testing of potential donors. AB - Patients' deaths due to the organ donor shortage make it imperative that every suitable organ be transplanted. False-positive results of tests for infection with the human immunodeficiency virus (HIV) result in lost organs. A survey of US organ procurement organizations collected the numbers of donors and ruled-out potential donors who had a positive result on an HIV test from January 1,2006, to October 31, 2008. Sixty-two percent of US organ procurement organizations participated. Of the 12397 donor/nondonor cases, 56 (0.45%) had an initial positive result on an HIV antibody or HIV nucleic acid test, and only 8 (14.3%) of those were confirmed positive. Of the false-positive results, 50% were from HIV antibody tests and 50% were from HIV nucleic acid tests. Organs are a scarce, finite, and perishable resource. Use of HIV antibody testing has produced a remarkably safe track record of avoiding HIV transmission, with 22 years of nonoccurrence between transmissions. Because false positives occur with any test, including the HIV Ab test, adding nucleic acid testing to the standard donor testing panel doubles the number of false-positive HIV test results and thus the number of medically suitable donors lost. The required HIV antibody test is 99.99% effective in preventing transmission of the HIV virus. Adding the HIV nucleic acid test to routine organ donor screening could result in as many as 761 to 1551 unnecessary deaths of patients between HIV transmission events because medically suitable organs are wasted. PMID- 21977886 TI - Infections in patients with chronic renal failure and kidney transplant recipients in Brazil. AB - Patients with chronic renal failure who are undergoing dialysis and kidney transplant recipients are susceptible to infection for several reasons. In this study, the profile of infections in patients with chronic renal failure and kidney transplant recipients treated at a hospital in northern Parana, Brazil, from 2007 to 2009 was examined. The study involved 187 patients: 59 kidney transplant recipients and 128 patients undergoing dialysis. The frequency of infection was 25% (32/128) in dialysis patients and 8% (5/59) in transplant recipients (P = .008). Staphylococcus aureus was the most prevalent infectious agent, cultured from 27% (13/48) of samples, followed by Escherichia coli at 17% (8/48). All isolates of S aureus were sensitive to vancomycin and resistant to penicillin, and 43% were resistant to oxacillin. Most S aureus samples (43%) were isolated from cultures of blood samples. As for the E coli, 75% were resistant to cephalothin and 38% were resistant to sulfamethoxazole/trimethoprim. Most isolates of E coli (62%) were cultured from specimens of patients with suspected urinary tract infection. PMID- 21977887 TI - Preoperative factors as predictors of blood product transfusion requirements in orthotopic liver transplantation. AB - CONTEXT: Intraoperative transfusion can affect the chance of graft survival in liver transplantation, a complicated operation with massive blood loss. Verification of factors that are predictive of intraoperative blood loss and transfusion increases the quality of anesthesia management. OBJECTIVE: To assess use of blood and blood products between 2002 and 2008 and to evaluate factors associated with blood loss and requirement for blood products in adult patients undergoing orthotopic liver transplantation via piggyback technique. DESIGN: Medical charts and anesthesia records from 261 eligible adult recipients of an orthotopic liver transplant between March 2002 and May 2008 were reviewed. SETTING: Shiraz Liver Transplantation Center, the only active liver transplantation center in Iran. MAIN OUTCOME MEASURES: Potential influencing factors in blood loss and transfusion, including sex, preoperative hemoglobin level, international normalized ratio, primary diagnosis, platelet count, creatinine level, Model for End-Stage Liver Disease (MELD) score, central venous pressure, and total anesthesia time, were measured and subjected to multivariable analysis. RESULTS: Mean blood loss was 54.2 (SD, 47.9) mL/kg, the mean (SD) for amounts of blood products transfused was 25.3 (19.5) mL/kg for packed red blood cells, 2.6 (3.3) units for fresh frozen plasma, and 1.7 (3.1) units for platelets. Seven recipients (2.7%) underwent transplantation without intraoperative transfusion of red blood cells, whereas 25 patients (9.6%) received more than 10 units of red blood cells intraoperatively. Multivariable analysis showed that no preoperative factor was a predictor of blood loss or requirement for intraoperative transfusion. Transfusion of fresh frozen plasma and packed red blood cells was significantly lower in 2005, 2006, 2007, and 2008 than in 2003 to 2004 (P < .001). PMID- 21977889 TI - Nurses already know what to do. PMID- 21977890 TI - A good investment. PMID- 21977888 TI - Quality of life in recipients before and after liver transplantation in Turkey. AB - CONTEXT: Liver transplantation has become the treatment of choice for patients with end-stage liver disease. Most studies show a positive effect on quality of life after liver transplantation, but most studies are based on data from Western countries and little is known about quality of life in liver transplant recipients in Turkey or other developing countries. OBJECTIVE: To investigate liver transplant recipients' quality of life and factors affecting it, before and 3 months after transplantation in western Turkey. DESIGN: Descriptive and comparative, with data collected prospectively. SETTING: Two medical centers in Western Turkey. PATIENTS: Sixty-five adult recipients of a liver transplant between May 15 and December 31,2007. INSTRUMENTS: Quality of life was measured by using the Nottingham Health Profile Turkish version, and sociodemographic and clinical data were collected from patients' records. RESULTS: Scores on all subscales of the Nottingham Health Profile differed significantly from before to after liver transplantation. The differences between the mean scores for quality of life before and after transplantation varied significantly with the patients' sex and disease severity. PMID- 21977891 TI - The pros and cons of routine. PMID- 21977892 TI - Engaging staff in the change process. AB - In this article the author, a ward sister, reports on an awayday held for staff on an acute ward in a children's hospital. An appreciative leadership approach was adopted to boost morale, improve standards, and motivate staff to take ownership of transforming the ward environment. PMID- 21977893 TI - Leadership scheme targets new nurse and midwifery graduates. AB - The Modernising Nursing Careers initiative offers development opportunities to recently registered nurses and midwives. The initiative has included a pilot for early clinical career fellowships, which has been running since 2007. Lessons from the pilot and from a national evaluation have led to an enhanced model of leadership development. The fellowship scheme has a rigorous selection process, an effective support infrastructure and requires candidates to study for a clinically relevant master's degree. Indicators from the pilot suggest fellows are appointed to higher grade posts early in their careers, suggesting that investing in nurses and midwives near the start of their working lives can bring forth a new generation of clinical leaders. A follow-up longitudinal study will use pilot findings to inform developments. PMID- 21977894 TI - A force for transformation. AB - Practice development resources are vital for nurse leaders wishing to bring changes in attitudes, practice and workplace culture to improve the patient experience. The Foundation of Nursing Studies (FoNS) provides nurse leaders with the support and resources to make such changes and this article sets out the main points of its new strategy for 2011/14. PMID- 21977895 TI - New barcode checks help reduce drug round errors in care homes. AB - A study undertaken between January 2008 and December 2010 evaluated the effects of a pharmacy-led barcode medication system in care homes (with or without on site registered nursing staff). The findings show that the system raised awareness of 'near miss' errors, particularly among nurses, and reduced stress and the pressure of medication rounds. Care staff in nursing homes, in particular, could administer selected medications using this system, but the development of a wider professional framework is recommended by the researchers at the University of the West of England and Warwick Medical School. PMID- 21977896 TI - Essential leadership skills for motivating and developing staff. AB - Achieving and sustaining high quality patient care and containing costs are important aspects of a nurse manager's role, and a successful manager needs to have the skills and ability to motivate and develop staff. This article focuses on how effective leadership can increase motivation and empowerment among nurses, examines the relevance of transformational leadership to motivation, and suggests practical ways of maintaining a motivated work environment. PMID- 21977897 TI - A private function. PMID- 21977899 TI - Filament-driven impulsive Raman spectroscopy. AB - Vibrational Raman spectroscopy is performed in the gas phase using a femtosecond laser pulse undergoing filamentation as an impulsive excitation source. The molecular coherence induced by the filamentary pulse is subsequently probed using a narrowband, sub-picosecond laser pulse to produce Raman spectra of gas phase species in a few tens of milliseconds (~10 laser shots). Pulse shortening with concomitant spectral broadening during filamentation results in a pulse that is both sufficiently short and of sufficient spectral power density to impulsively excite the highest energy ground state vibrations (up to 4158 cm(-1) corresponding to H(2)). Gas phase detection of chloroform, methylene chloride, cyclohexane, toluene, pentane, triethylamine, ammonia, nitromethane, and gasoline is performed. PMID- 21977898 TI - Evidence based post graduate training. A systematic review of reviews based on the WFME quality framework. AB - BACKGROUND: A framework for high quality in post graduate training has been defined by the World Federation of Medical Education (WFME). The objective of this paper is to perform a systematic review of reviews to find current evidence regarding aspects of quality of post graduate training and to organise the results following the 9 areas of the WFME framework. METHODS: The systematic literature review was conducted in 2009 in Medline Ovid, EMBASE, ERIC and RDRB databases from 1995 onward. The reviews were selected by two independent researchers and a quality appraisal was based on the SIGN tool. RESULTS: 31 reviews met inclusion criteria. The majority of the reviews provided information about the training process (WFME area 2), the assessment of trainees (WFME area 3) and the trainees (WFME area 4). One review covered the area 8 'governance and administration'. No review was found in relation to the mission and outcomes, the evaluation of the training process and the continuous renewal (respectively areas 1, 7 and 9 of the WFME framework). CONCLUSIONS: The majority of the reviews provided information about the training process, the assessment of trainees and the trainees. Indicators used for quality assessment purposes of post graduate training should be based on this evidence but further research is needed for some areas in particular to assess the quality of the training process. PMID- 21977900 TI - Alternative treatment of gluteofemoral fistulas using honey: a case report. AB - Perianal fistula is a common disease that affects particular patients with inflammatory bowel disease. Honey has been used as a natural remedy for centuries for the treatment of various disorders. We report a patient with persistent fistulas, in whom conventional medical and surgical therapy failed. In this case, most of fistulas in gluteofemoral region were completely healed and closed after 6 months of treatment with honey. In addition, honey reduced inflammation, pain and induration of affected region. This medical approach positively affected patient's mental condition and also improved his quality of life. PMID- 21977901 TI - Two-step route to indoles and analogues from haloarenes: a variation on the Fischer indole synthesis. AB - In a new variation on the Fischer indole synthesis, readily available haloarenes are converted into a wide range of indoles in just two steps by halogen-magnesium exchange and quenching with di-tert-butyl azodicarboxylate, followed by reaction with aldehydes or ketones under acidic conditions. The protocol, which is readily extended to the preparation of indole isosteres, 4- and 6-azaindoles and thienopyrroles, obviates the need to prepare potentially toxic aryl hydrazines, simultaneously avoiding undesirable anilines such as naphthylamines. PMID- 21977902 TI - Career shift phenomenon among doctors in tacloban city, philippines: lessons for retention of health workers in developing countries. AB - BACKGROUND: At the height of the global demand for nurses in the 1990s, a phenomenon of grave concern arose. A significant number of medical doctors in the Philippines shifted careers in order to seek work as nurses overseas. The obvious implications of such a trend require inquiry as to the reasons for it; hence, this cross-sectional study. The data in the study compared factors such as personal circumstances, job satisfaction/dissatisfaction, perceived benefits versus costs of the alternative job, and the role of social networks/linkages among doctors classified as career shifters and non-shifters. METHODOLOGY: A combined qualitative and quantitative method was utilized in the study. Data gathered came from sixty medical doctors practicing in three major hospitals in Tacloban City, Philippines, and from a special nursing school also located in the same city. Respondents were chosen through a non-probability sampling, specifically through a chain referral sampling owing to the controversial nature of the research. A set of pre-set criteria was used to qualify doctors as shifters and non-shifters. Cross-tabulation was carried out to highlight the differences between the two groups. Finally, the Wilcoxon-Mann-Whitney test was utilized to assess if these differences were significant. RESULTS: Among the different factors investigated, results of the study indicated that the level of job satisfaction or dissatisfaction and certain socio-demographic factors such as age, length of medical practice, and having children to support, were significantly different among shifters and non-shifters at p <= 0.05. This suggested that such factors had a bearing on the intention to shift to a nursing career among physicians. CONCLUSION: Taken in the context of the medical profession, it was the level of job satisfaction/dissatisfaction that was the immediate antecedent in the intention to shift careers among medical doctors. Personal factors, specifically age, support of children, and the length of medical practice gained explanatory power when they were linked to job satisfaction or dissatisfaction. On the other hand, factors such as perceived benefits and costs of the alternative job and the impact of social networks did not differ between shifters and non-shifters. It would then indicate that efforts to address the issue of physician retention need to go beyond economic incentives and deal with other sources of satisfaction or dissatisfaction among practicing physicians. Since this was an exploratory study in a particular locale in central Philippines, similar studies in other parts of the country need to be done to gain better understanding of this phenomenon at a national level. PMID- 21977903 TI - Quasiemulsion-templated formation of alpha-Fe2O3 hollow spheres with enhanced lithium storage properties. AB - alpha-Fe(2)O(3) hollow spheres with sheet-like subunits are synthesized by a facile quasiemulsion-templated method. Glycerol is dispersed in water to form oil in-water quasiemulsion microdroplets, which serve as soft templates for the deposition of the alpha-Fe(2)O(3) shell. When tested as anode materials for lithium-ion batteries, these alpha-Fe(2)O(3) hollow spheres manifest greatly enhanced Li storage properties. PMID- 21977904 TI - Isolated Hb Providence beta82Asn and beta82Asp fractions are more stable than native HbA(0) under oxidative stress conditions. AB - We have previously shown that hydrogen peroxide (H(2)O(2)) triggers irreversible oxidation of amino acids exclusive to the beta-chains of purified human hemoglobin (HbAo). However, it is not clear, whether alpha- or beta-subunit Hb variants exhibit different oxidative resistance to H(2)O(2) when compared to their native HbAo. Hb Providence contains two beta-subunit variants with single amino acid mutations at betaLys82->Asp (betaK82D) and at betaLys82->Asn (betaK82N) positions and binds oxygen at lower affinity than wild type HbA. We have separated Hb Providence into its 3 component fractions, and contrasted oxidative reactions of its beta-mutant fractions with HbAo. Relative to HbAo, both betaK82N and betaK82D fractions showed similar autoxidation kinetics and similar initial oxidation reaction rates with H(2)O(2). However, a more profound pattern of changes was seen in HbAo than in the two Providence fractions. The structural changes in HbAo include a collapse of beta-subunits, and alpha-alpha dimer formation in the presence of excess H(2)O(2). Mass spectrometric and amino acid analysis revealed that betaCys93 and betaCys112 were oxidized in the HbAo fraction, consistent with oxidative pathways driven by a ferrylHb and its protein radical. These amino acids were oxidized at a lesser extent in betaK82D fraction. While the 3 isolated components of Hb Providence exhibited similar ligand binding and oxidation reaction kinetics, the variant fractions were more effective in consuming H(2)O(2) and safely internalizing radicals through the ferric/ferryl pseudoperoxidase cycle. PMID- 21977905 TI - Caught in the act: covalent cross-linking captures activator-coactivator interactions in vivo. AB - Currently there are few methods suitable for the discovery and characterization of transient, moderate affinity protein-protein interactions in their native environment, despite their prominent role in a host of cellular functions including protein folding, signal transduction, and transcriptional activation. Here we demonstrate that a genetically encoded photoactivatable amino acid, p benzoyl-l-phenylalanine, can be used to capture transient and/or low affinity binding partners in an in vivo setting. In this study, we focused on ensnaring the coactivator binding partners of the transcriptional activator VP16 in S. cerevisiae. The interactions between transcriptional activators and coactivators in eukaryotes are moderate in affinity and short-lived, and due in part to these characteristics, identification of the direct binding partners of activators in vivo has met with only limited success. We find through in vivo photo-cross linking that VP16 contacts the Swi/Snf chromatin-remodeling complex through the ATPase Snf2(BRG1/BRM) and the subunit Snf5 with two distinct regions of the activation domain. An analogous experiment with Gal4 reveals that Snf2 is also a target of this activator. These results suggest that Snf2 may be a valuable target for small molecule probe discovery given the prominent role the Swi/Snf complex family plays in development and in disease. More significantly, the successful implementation of the in vivo cross-linking methodology in this setting demonstrates that it can be applied to the discovery and characterization of a broad range of transient and/or modest affinity protein-protein interactions. PMID- 21977906 TI - Palladium-catalyzed 1,4-addition of diarylphosphines to alpha,beta-unsaturated aldehydes. AB - A highly stereoselective asymmetric 1,4-addition of diarylphosphines to alpha,beta-unsaturated aldehydes catalyzed by a bis(phosphine) pincer-Pd complex has been developed for the synthesis of chiral phosphines with excellent stereoselectivity (up to 98% ee) under mild conditions. The application of the current method to the synthesis of enantiopure bisphosphine and its pincer-Pd complex has also been demonstrated. PMID- 21977908 TI - Methylation-specific multiplex ligation-dependent probe amplification and identification of deletion genetic subtypes in Prader-Willi syndrome. AB - PURPOSE: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are complex neurodevelopmental disorders caused by loss of expression of imprinted genes from the 15q11-q13 region depending on the parent of origin. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) kits from MRC-Holland (Amsterdam, The Netherlands) were used to detect PWS and AS deletion subtypes. We report our experience with two versions of the MS-MLPA-PWS/AS kit (original A1 and newer B1) in determining methylation status and deletion subtypes in individuals with PWS. METHODS: MS-MLPA analysis was performed on DNA isolated from a large cohort of PWS subjects with the MS-MLPA-PWS/AS-A1 and -B1 probe sets. RESULTS: Both MS-MLPA kits will identify deletions in the 15q11-q13 region but the original MS-MLPA-A1 kit has a higher density of probes at the telomeric end of the 15q11-q13 region, which is more useful for identifying individuals with atypical deletions. The newer B1 kit contains more probes in the imprinting center (IC) and adjoining small noncoding RNAs useful in identifying small microdeletions. CONCLUSION: The A1 kit identified the typical deletions and smaller atypical deletions, whereas the B1 kit was more informative for identifying microdeletions including the IC and SNORD116 regions. Both kits should be made available for accurate characterization of PWS/AS deletion subtypes as well as evaluating for IC and SNORD116 microdeletions. PMID- 21977909 TI - Structure formation in metal complex/polymer hybrid nanomaterials prepared by miniemulsion. AB - Polymer/complex hybrid nanostructures were prepared using a variety of hydrophobic metal beta-diketonato complexes. The mechanism of structure formation was investigated by electron paramagnetic resonance (EPR) spectroscopy and small angle X-ray scattering (SAXS) in the liquid phase. Structure formation is attributed to an interaction between free coordination sites of metal beta diketonato complexes and coordinating anionic surfactants. Lamellar structures are already present in the miniemulsion. By subsequent polymerization the lamellae can be embedded in a great variety of different polymeric matrices. The morphology of the lamellar structures, as elucidated by transmission electron microscopy (TEM), can be controlled by the choice of anionic surfactant. Using sodium alkylsulfates and sodium dodecylphosphate, "nano-onions" are formed, while sodium carboxylates lead to "kebab-like" structures. The composition of the hybrid nanostructures can be described as bilayer lamellae, embedded in a polymeric matrix. The metal complexes are separated by surfactant molecules which are arranged tail-to-tail; by increasing the carbon chain length of the surfactant the layer distance of the structured nanomaterial can be adjusted between 2 and 5 nm. PMID- 21977910 TI - Inactivation of the AMP-activated protein kinase by glucose in cardiac myocytes: a role for the pentose phosphate pathway. AB - Incubation of adult rat cardiac myocytes with increasing glucose concentrations decreased phosphorylation (alphaThr172) and activity of AMPK (AMP-activated protein kinase). The effect could be demonstrated without measurable changes in adenine nucleotide contents. The glucose effect was additive to the decrease in AMPK activity caused by insulin, was attenuated by adrenaline, was not mimicked by glucose analogues, lactate or pyruvate and was not due to changes in myocyte glycogen content. AMPK activity was decreased by xylitol and PMS (phenazine methosulfate) and was increased by the glucose-6-phosphate dehydrogenase inhibitor DHEA (dehydroepiandrosterone) and by thiamine. PMS and DHEA respectively, increased and decreased CO2 formation by the PPP (pentose phosphate pathway). AMPK activity was inversely related to the myocyte content of Xu5P (xylulose 5-phosphate), an intermediate of the non-oxidative arm of the PPP. Endothall, an inhibitor of PP2A (protein phosphatase 2A), abolished the glucose effect on AMPK activity. Further studies are needed to define the 'active component' that mediates the glucose effect and whether its site of action is PP2A. PMID- 21977911 TI - Yin yang-1 regulates the characterized murine focal adhesion-associated protein promoter. AB - The focal adhesion-associated protein (FAAP), product of the murine D10Wsu52e gene, is involved in modulating cell adhesion dynamics. The ubiquitously expressed protein belongs to the highly conserved UPF0027 family, the newly identified RNA >p ligase family. To understand the mechanisms underlying FAAP expression and regulation, we first mapped its major transcription start site at the nucleotide 79 bp upstream of the ATG codon. The murine FAAP 2.1 kb 5' flanking region was cloned, analyzed, and aligned with the corresponding 1.7 kb region of its human homolog HSPC117. Despite the differences in activity, cell in vitro transfection and testis in vivo electroporation identified a 0.2 kb efficient promoter region lacking a functional TATA-box. Gel shift assays confirmed the specific interaction between Yin Yang-1 (YY1) and the potential element in the proximal region of the FAAP promoter. Site mutation, truncation, RNAi, and overexpression analyses suggested that YY1 is an important regulator of the FAAP promoter. PMID- 21977912 TI - Chlorogenic acid differentially affects postprandial glucose and glucose dependent insulinotropic polypeptide response in rats. AB - Regular coffee consumption significantly lowers the risk of type 2 diabetes (T2D). Coffee contains thousands of compounds; however, the specific component(s) responsible for this reduced risk is unknown. Chlorogenic acids (CGA) found in brewed coffee inhibit intestinal glucose uptake in vitro. The objective of this study was to elucidate the mechanisms by which CGA acts to mediate blood glucose response in vivo. Conscious, unrestrained, male Sprague-Dawley rats were chronically catheterized and gavage-fed a standardized meal (59% carbohydrate, 25% fat, 12% protein), administered with or without CGA (120 mg.kg(-1)), in a randomized crossover design separated by a 3-day washout period. Acetaminophen was co-administered to assess the effects of CGA on gastric emptying. The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were measured. GLP-1 response in the presence of glucose and CGA was further examined, using the human colon cell line NCI-H716. Total area under the curve (AUC) for blood glucose was significantly attenuated in rats fed CGA (p < 0.05). Despite this, no differences in plasma insulin or nonesterified fatty acids were observed, and gastric emptying was not altered. Plasma GIP response was blunted in rats fed CGA, with a lower peak concentration and AUC up to 180 min postprandially (p < 0.05). There were no changes in GLP-1 secretion in either the in vivo or in vitro study. In conclusion, CGA treatment resulted in beneficial effects on blood glucose response, with alterations seen in GIP concentrations. Given the widespread consumption and availability of coffee, CGA may be a viable prevention tool for T2D. PMID- 21977913 TI - Borg's scales in strength training; from theory to practice in young and older adults. AB - This study is the first to apply Borg's psychophysical equation to measuring responses to strength training with weights machines. Theoretical constructs of Borg's scales were assessed in younger and older adults to estimate the appropriate load and number of repetitions required to meet recommended practice guidelines. A younger group (YG; 20 males, 20 females; aged 19-38 years) and older group (OG; 13 males, 13 females; aged 50-75 years) participated in 3 experiments. Experiment 1: YG performed 2-repetitions of incremented loads during triceps-elbow extensions and knee extensions to level 7 on Borg's CR10 Scale. Experiment 2: YG (n = 16) then performed 12-repetitions at the loads from experiment 1 that elicited CR10 ratings 1.5, 3.0, and 5.0. Experiment 3: OG performed 15-repetitions of "lat-pull" and leg press at 15-repetition maximum (RM) load. In experiments 2 and 3, CR10 or Borg RPE were measured every 2 repetitions. Experiment 1 revealed classic psychophysical response growth exponents between 1.1 and 1.8, which were greater in arms than legs (p < 0.001) and in females (p < 0.001). Theoretical estimates of 1RM were derived from the growth curves for the weights eliciting CR10 ratings of 1.5, 3, and 5. CR10 ratings of 3 to 6 fell within estimates of 40%-70% 1RM. Experiments 2 and 3 revealed, for constant load exercise "over time" (12 and 15 repetitions) from an initial CR10 rating of 4 to 6, a linear increase of 1 scale point for every 3 to 4 repetitions. In conclusion, Borg's equation has been used to set theoretical estimates of a %1RM. Relevant to current practice guidelines was the ability to set appropriate loads in relation to performing recommended numbers of repetitions (e.g., if the CR10 rating is >6 after 2 repetitions, the weight is likely be too heavy to complete 12 to 15 repetitions). PMID- 21977914 TI - Topical fluticasone propionate: intervention and maintenance treatment options of atopic dermatitis based on a high therapeutic index. AB - Fluticasone propionate (FP), a medium potent glucocorticoid (class III) of carbothioate nature with a favourable benefit/risk ratio, has emerged as a standard medication for the topical treatment of inflammatory skin disorders, in particular atopic dermatitis (AD). FP is available as a 0.05% cream and a 0.005% ointment formulation. The glucocorticoid is characterized by high lipophilicity, high affinity binding to the glucocorticoid receptor and a rapid hepatic biotransformation. Though skin blanching following topical application of FP surpasses that given with glucocorticoids of medium strength, clinical trials show a low potential of FP for local and systemic adverse effects. Even in paediatric patients with AD as well as in difficult-to-treat areas like face, eyelids and intertriginous areas, FP proved to be both effective and safe. Thus, the therapeutic effects of FP clearly outweigh the unwanted effects. Correspondingly, a therapeutic index of 2.0 can be attributed to this glucocorticoid. In this respect, topical FP does not differ from other topical glucocorticoids with increased benefit-to-risk ratio, e.g. prednicarbate, methylprednisolone aceponate and mometasone furoate. However, randomized controlled trials do not only support conventional intervention but also innovative maintenance treatment. PMID- 21977915 TI - Expression, localization and polymorphisms of the nuclear receptor PXR in Barrett's esophagus and esophageal adenocarcinoma. AB - BACKGROUND: The continuous exposure of esophageal epithelium to refluxate may induce ectopic expression of bile-responsive genes and contribute to the development of Barrett's esophagus (BE) and esophageal adenocarcinoma. In normal physiology of the gut and liver, the nuclear receptor Pregnane * Receptor (PXR) is an important factor in the detoxification of xenobiotics and bile acid homeostasis. This study aimed to investigate the expression and genetic variation of PXR in reflux esophagitis (RE), Barrett's esophagus (BE) and esophageal adenocarcinoma. METHODS: PXR mRNA levels and protein expression were determined in biopsies from patients with adenocarcinoma, BE, or RE, and healthy controls. Esophageal cell lines were stimulated with lithocholic acid and rifampicin. PXR polymorphisms 25385C/T, 7635A/G, and 8055C/T were genotyped in 249 BE patients, 233 RE patients, and 201 controls matched for age and gender. RESULTS: PXR mRNA levels were significantly higher in adenocarcinoma tissue and columnar Barrett's epithelium, compared to squamous epithelium of these BE patients (P<0.001), and RE patients (P=0.003). Immunohistochemical staining of PXR showed predominantly cytoplasmic expression in BE tissue, whereas nuclear expression was found in adenocarcinoma tissue. In cell lines, stimulation with lithocholic acid did not increase PXR mRNA levels, but did induce nuclear translocation of PXR protein. Genotyping of the PXR 7635A/G polymorphism revealed that the G allele was significantly more prevalent in BE than in RE or controls (P=0.037). CONCLUSIONS: PXR expresses in BE and adenocarcinoma tissue, and showed nuclear localization in adenocarcinoma tissue. Upon stimulation with lithocholic acid, PXR translocates to the nuclei of OE19 adenocarcinoma cells. Together with the observed association of a PXR polymorphism and BE, this data implies that PXR may have a function in prediction and treatment of esophageal disease. PMID- 21977917 TI - Giant pumping of single-file water molecules in a carbon nanotube. AB - Achieving a fast, unidirectional flow of single-file water molecules (UFSWM) across nanochannels is important for membrane-based water purification or seawater desalination. For this purpose, electro-osmosis methods are recognized as a very promising approach and have been extensively discussed in the literature. Utilizing molecular dynamics simulations, here we propose a design for pumping water molecules in a single-walled carbon nanotube in the presence of a linearly gradient electric (GE) field. Such a GE field is inspired by GE fields generated from charged ions located adjacent to biological membrane water nanochannels that can conduct water in and out of cells and can be experimentally achieved by using the charged tip of an atomic force microscope. As a result, the maximum speed of the UFSWM can be 1 or 2 orders of magnitude larger than that in a uniform electric (UE) field. Also, inverse transportation of water molecules does not exist in case of the GE field but can appear for the UE field. Thus, the GE field yields a much more efficient UFSWM than the UE field. The giant pumping ability as revealed is attributed to the nonzero net electrostatic force acting on each water molecule confined in the nanotube. These observations have significance for the design of nanoscale devices for readily achieving controllable UFSWM at high speed. PMID- 21977916 TI - Antimalarial beta-carboline and indolactam alkaloids from Marinactinospora thermotolerans, a deep sea isolate. AB - Four new beta-carboline alkaloids, designated marinacarbolines A-D (1-4), two new indolactam alkaloids, 13-N-demethyl-methylpendolmycin (5) and methylpendolmycin 14-O-alpha-glucoside (6), and the three known compounds 1-acetyl-beta-carboline (7), methylpendolmycin (8), and pendolmycin (9) were obtained from the fermentation broth of Marinactinospora thermotolerans SCSIO 00652, a new actinomycete belonging to the family Nocardiopsaceae. Their structures were elucidated by extensive MS and 1D and 2D NMR spectroscopic data analyses. The structure of compound 1 was further confirmed by single-crystal X-ray crystallography. The new compounds 1-6 were inactive against a panel of eight tumor cell lines (IC50>50 MUM) but exhibited antiplasmodial activities against Plasmodium falciparum lines 3D7 and Dd2, with IC50 values ranging from 1.92 to 36.03 MUM. PMID- 21977918 TI - Mussel-inspired chemistry for robust and surface-modifiable multilayer films. AB - In this article, we report a bioinspired approach to preparing stable, functional multilayer films by the integration of mussel-inspired catechol oxidative chemistry into a layer-by-layer (LbL) assembly. A polyanion of poly(acrylic acid g-dopamine) (PAA-dopamine) bearing catechol groups, a mussel adhesive protein mimetic polymer, was synthesized as the building block for LbL assembly with poly(allylamine hydrochloride) (PAH). The oxidization of the incorporated catechol group under mild oxidative condition yields o-quinone, which exhibits high reactivity with amine and catechol, thus endowing the chemical covalence and retaining the assembled morphology of multilayer films. The cross-linked films showed excellent stability even in extremely acidic, basic, and highly concentrated aqueous salt solutions. The efficient chemical cross-linking allows for the production of intact free-standing films without using a sacrificial layer. Moreover, thiol-modified multilayer films with good stability were exploited by a combination of thiols-catechol addition and then oxidative cross linking. The outstanding stability under harsh conditions and the facile functionalization of the PAA-dopamine/PAH multilayer films make them attractive for barriers, separation, and biomedical devices. PMID- 21977919 TI - Pyogenic granuloma presenting as an orbital mass. AB - Pyogenic granuloma (PG) of the eyelid and orbit is typically associated with trauma or surgery. We report a rare case of an orbital intraconal PG arising de novo in association with an orbital artery. PMID- 21977923 TI - Effects of a single post-partum injection of a high dose of vitamin D on glucose tolerance and insulin resistance in mothers with first-time gestational diabetes mellitus. AB - AIM: This study was performed to determine the effect of a single, large, intramuscular injection of vitamin D post-partum on glucose tolerance and insulin resistance in women with gestational diabetes. METHODS: Forty-five participants in a randomized controlled trial on gestational diabetes mellitus were divided into an intervention group and a control group. Only subjects in the intervention group received one intramuscular injection of 300,000 IU of vitamin D3. HbA(1c), serum 25-hydroxyvitamin D3, fasting insulin and blood glucose, C-peptide, homeostasis model assessment insulin resistance index (HOMA-IR), beta-cell function, insulin sensitivity and the Quantitative Insulin Sensitivity Check Index (QUICKI) were measured at baseline and after 3 months of intervention. RESULTS: Approximately 80% of the mothers had a degree of vitamin D deficiency. Post-intervention, this was found in 4.2 and 71.4% in the intervention and control groups, respectively. The medians of HOMA-IR indices before and after intervention were 0.6 and 0.5 (P = 0.7), respectively, in subjects in the intervention group, and 0.5 and 0.9 (P = 0.01) in subjects in the control group. The mean of the QUICKI fell only in the control group (P = 0.008). In the control group, beta-cell function increased by ~8% (P = 0.01) and insulin sensitivity decreased after 3 months (P = 0.002). Post-intervention, the median C-peptide decreased in the intervention group and increased in the control group, but the change was significant only in the control group (P = 0.03). CONCLUSIONS: A single injection of 300,000 IU of vitamin D3 achieves a 3-month serum 25 hydroxyvitamin D range of 50-80 nmol/l and is an efficient, effective and safe procedure for improving the vitamin status and indices of insulin resistance in mothers with gestational diabetes after delivery. PMID- 21977924 TI - Dose-response assessment for influenza A virus based on data sets of infection with its live attenuated reassortants. AB - Reported data sets on infection of volunteers challenged with wild-type influenza A virus at graded doses are few. Alternatively, we aimed at developing a dose response assessment for this virus based on the data sets for its live attenuated reassortants. Eleven data sets for live attenuated reassortants that were fit to beta-Poisson and exponential dose-response models. Dose-response relationships for those reassortants were characterized by pooling analysis of the data sets with respect to virus subtype (H1N1 or H3N2), attenuation method (cold-adapted or avian-human gene reassortment), and human age (adults or children). Furthermore, by comparing the above data sets to a limited number of reported data sets for wild-type virus, we quantified the degree of attenuation of wild-type virus with gene reassortment and estimated its infectivity. As a result, dose-response relationships of all reassortants were best described by a beta-Poisson model. Virus subtype and human age were significant factors determining the dose response relationship, whereas attenuation method affected only the relationship of H1N1 virus infection to adults. The data sets for H3N2 wild-type virus could be pooled with those for its reassortants on the assumption that the gene reassortment attenuates wild-type virus by at least 63 times and most likely 1,070 times. Considering this most likely degree of attenuation, 10% infectious dose of H3N2 wild-type virus for adults was estimated at 18 TCID50 (95% CI = 8.8 35 TCID50). The infectivity of wild-type H1N1 virus remains unknown as the data set pooling was unsuccessful. PMID- 21977925 TI - Effect of the treatment with allopurinol on the endothelial function in patients with hyperuricemia. AB - BACKGROUND: Hyperuricemia has been associated with an increased risk of endothelial dysfunction (ED), cardiovascular and renal disease. The role of uric acid (UA) on vascular damage is still controversial because previous studies have included patients with other risk factor for ED. OBJECTIVE: To determine if the treatment with allopurinol improved endothelial function in hyperuricemic patients without other risk factors for ED. MATERIAL AND METHODS: In order to gain more insight about the contribution of UA to the ED, we screened 369 apparently healthy male individuals for UA in a period of 9 months. Only 9 patients fulfill the inclusion criteria: UA plasma levels > 7 mg/dL without other risk factors for ED such as hypercholesterolemia, obesity, diabetes and hypertension. RESULTS: Endothelial function, assessed by flow mediated dilatation (FMD) in the brachial artery improved significantly after 30 days of allopurinol treatment (9.6% [6.3-13.3%] vs. 13.7% [11-14.7%], p = 0.036), concomitantly with a decrease of about 45% in the uric acid plasma levels. Other parameters were not modified by allopurinol treatment. Any No significant correlation was found (r = 0.367, p = 0.33) between the DeltaUA plasma levels (UA after treatment - UA in basal conditions) and DeltaFMD (FMD after treatment - FMD in basal conditions). CONCLUSIONS: These results strongly suggest that allopurinol improves flow mediated vasodilation regardless of uric acid plasma concentrations. PMID- 21977926 TI - WWII and the home front: the intersection of history and biography. PMID- 21977927 TI - What does living in a democracy mean for kids? PMID- 21977928 TI - Toward a science of citizenship. PMID- 21977929 TI - A health promotion curriculum for adolescent young citizens: deliberation and public action for HIV/AIDS-competent communities. PMID- 21977930 TI - The well-being of young people and their parents amid tough times: views from Spain. PMID- 21977931 TI - Generational differences in mental health: are children and adolescents suffering more, or less? AB - Almost all of the available evidence suggests a sharp rise in anxiety, depression, and mental health issues among Western youth between the early 20th century and the early 1990s. Between the early 1990s and the present, more serious problems such as suicide and depression have receded in some data sets, whereas feeling overwhelmed and reporting psychosomatic complaints have continued to increase. Other indicators, such as anxiety, have remained at historically high levels but not continued to increase. This mixed pattern of results may be rooted in the increasing use of antidepressants and therapy and the improvement in some cultural indicators. However, the incidence of youth mental health problems remains unacceptably high. PMID- 21977932 TI - Fostering young people's support for participatory human rights through their developmental niches. AB - The last 6 decades of empirical research on civic engagement among young people living in democracies and of the recognition of international human rights have seen the achievement of many milestones. This article focuses on some connections between these 2 areas and examines the ways in which everyday settings such as neighborhoods and the schools that exist within them can foster support for human rights (especially the practice of participatory rights) among adolescents. Secondary analysis of the International Association for the Evaluation of Educational Achievement Civic Education (CIVED) Study (data collected in 1999 from nationally representative samples of 14-year-olds in 28 countries) is presented. A cluster analysis of 12 attitudinal scales in 5 countries sharing the Western European tradition (Australia, England, Finland, Sweden, and the United States) is presented. A new conceptual model is also introduced, a modification of Super and Harkness's Developmental Niche. This model frames an analysis unpacking some findings from the CIVED Study and focusing on the everyday experiences and neighborhood niches for the development of participatory human rights. The larger message is that research on social justice attitudes among young people is a valuable form of social advocacy and action. PMID- 21977933 TI - Hospitality and the mental health of children and families. AB - In many ancient cultures, hospitality was a significant moral and religious practice in responding to the needs of strangers. Although largely trivialized in contemporary society, the practice of hospitality continues to create contexts that contribute to individual and communal flourishing and that resist several dehumanizing social trends. A recovery of the practice can help faith communities connect their moral and theological commitments to the needs of children, families, and neighborhoods. PMID- 21977934 TI - Racial and cultural factors affecting the mental health of Asian Americans. AB - In this study, we employed structural equation modeling to test the degree to which racism-related stress, acculturative stress, and bicultural self-efficacy were predictive of mental health in a predominantly community-based sample of 367 Asian American adults. We also tested whether bicultural self-efficacy moderated the relationship between acculturative stress and mental health. Finally, we examined whether generational status moderated the impact of racial and cultural predictors of mental health by testing our model across immigrant and U.S.-born samples. Results indicated that our hypothesized structural model represented a good fit to the total sample data. While racism-related stress, acculturative stress, and bicultural self-efficacy were significant predictors of mental health in the total sample analyses, our generational analyses revealed a differential predictive pattern across generational status. Finally, we found that the buffering effect of bicultural self-efficacy on the relationship between acculturative stress and mental health was significant for U.S.-born individuals only. Implications for research and service delivery are explored. PMID- 21977935 TI - Discrimination, attribution, and racial group identification: implications for psychological distress among Black Americans in the National Survey of American Life (2001-2003). AB - There is increasing evidence that experiencing discrimination may contribute to poor mental health among Black Americans. However, few studies have distinguished between discrimination attributed to race versus other forms of discrimination or have compared differences in their psychological implications. Using nationally representative data on 5,191 Black Americans in the National Survey of American Life (NSAL; 2001-2003), this study examined serious psychological distress (SPD) in relation to discrimination attributed to racial versus nonracial causes and also investigated whether racial group identification may be a buffer. We found that discrimination was associated with greater odds of SPD, regardless of attribution. Racial attributions were associated with higher odds of SPD compared with attributions to nonracial causes for each level of discrimination. High racial group identification buffered the negative effect of moderate levels of both racially and nonracially attributed discrimination. Our results provide evidence for the negative influence of discrimination on SPD among Black Americans and indicate that high racial group identification may somewhat mitigate their negative mental health effects. Our study suggests that discrimination and racial group identification should be addressed to protect against psychological distress among Black Americans. PMID- 21977936 TI - Goal-striving stress and the mental health of college-educated Black American men: the protective effects of system-blame. AB - The present study examined the relationship between goal-striving stress and well being in a survey of 399 college-educated Black American men who were members of a Black fraternal organization. Regression analyses revealed that goal-striving stress was associated with decreased psychological well-being, controlling for demographics and various psychosocial factors. When asked to explain their failure to reach life goals, half of the men attributed setbacks to racial discrimination. The association of goal-striving stress with diminished well being was stronger among those who did not attribute setbacks to race than among those who did. These findings suggest that even with material success, Black men face blocked opportunities that could be consequential to their well-being. PMID- 21977937 TI - "Just be straight with me:" an exploration of Black patient experiences in initial mental health encounters. AB - It is advantageous for a clinician to understand how patients feel about their initial encounters, but it can be difficult to discern what is and what is not working. This qualitative, exploratory study is guided by the question, "What happens during an initial mental health encounter between a Black patient and a non-Black provider that leads the patient to describe it as a good or poor experience?" The findings are based on face-to-face, postintake interviews with 14 Black patients seen by 11 non-Black providers as part of the Patient-Provider Encounter Study. The objective is to explore the initial interpersonal interactions between Black patients and their non-Black mental health providers and to better understand how patients come to describe the encounter as good (favorable) or poor (unfavorable). A framework inclusive of 5 specific elements is introduced that maps the patient's conceptualization process about how judgments are made about the encounter. Owing to the naturalistic and exploratory nature of the study, a research hypothesis was not established. Instead, we observed how patients scanned the interaction with the provider, made assessments about their provider, and determined whether their experience was positive or negative. The implications of these findings will help to improve the interactions in mental health settings between minority patients and their providers. PMID- 21977938 TI - Discrimination and Latino psychological distress: the moderating role of ethnic identity exploration and commitment. AB - This study sought to examine the moderating effect of ethnic identity exploration and ethnic identity commitment on the various types of discrimination and psychological distress within a sample of Latino adults (N = 397). The results revealed that ethnic identity exploration was associated with increased psychological distress within the context of discrimination in work, academic, and public settings. Ethnic identity commitment, on the other hand, served as a buffer between covert discrimination and mental health. These findings highlight the circumstances in which ethnic identity functioned as a protective and as a risk factor in the psychological distress of Latinos. The implications are discussed within a stress and coping framework and outline directions for future research. PMID- 21977939 TI - A culturally competent relaxation intervention for Latino/as: assessing a culturally specific match model. AB - In this study, we explored 2 questions: (a) Consistent with the cultural match theory (CMT), did treatment adherence and outcome improve as discrepancies between the cultural features of an anxiety treatment and patient characteristics decreased, and (b) In agreement with the specific therapy ingredient model (STIM), did the psychotherapeutic outcomes of a Culturally Competent Relaxation Intervention (CCRI) designed to reduce anxiety more effectively reduce anxiety rather than depression symptoms? The CCRI includes allocentric (the tendency to define oneself in relationship to others) relaxation interventions, while traditional relaxation strategies employ idiocentric (the tendency to define oneself in isolation from others) relaxation interventions. The CCRI was assessed with 44 Latino/a adults of low socioeconomic backgrounds. The results supported 2 hypotheses: (a) Based on the CMT, a relationship was found between participants' levels of allocentrism and their consequent levels of treatment adherence, and (b) Consistent with the STIM, treatment adherence on the CCRI was correlated with reductions in anxiety, but not with depressive symptoms. These findings are discussed with a focus on future efforts to create culturally competent interventions. PMID- 21977940 TI - Meeting the mental health needs of low-income immigrants in primary care: a community adaptation of an evidence-based model. AB - Low-income, uninsured immigrants are burdened by poverty and a high prevalence of trauma exposure and thus are vulnerable to mental health problems. Disparities in access to mental health services highlight the importance of adapting evidence based interventions in primary care settings that serve this population. In 2005, the Montgomery Cares Behavioral Health Program began adapting and implementing a collaborative care model for the treatment of depression and anxiety disorders in a network of primary care clinics that serve low-income, uninsured residents of Montgomery County, Maryland, the majority of whom are immigrants. In its 6th year now, the program has generated much needed knowledge about the adaptation of this evidence-based model. The current article describes the adaptations to the traditional collaborative care model that were necessitated by patient characteristics and the clinic environment. PMID- 21977942 TI - The prevalence of interdigital erythrasma in southern region of Turkey. AB - BACKGROUND: Erythrasma is a skin infection which is caused by Corynebacterium minutissimum. Interdigital erythrasma is the most common form. OBJECTIVE: The aim of this study was to detect the frequency and risk factors of interdigital erythrasma in patients with clinically suspected tinea pedis. METHODS: This study was conducted between June and December 2010 and included 122 patients who had interdigital foot lesions. All patients were examined using a Wood's lamp. The smears were stained using Gram's method. Direct examination was performed using 20% potassium hydroxide. Sabouraud dextrose agar and brain heart infusion agar were used for cultures. Moreover, the demographical characteristics of patients, concomitant diseases and clinical findings were also recorded. Cases that were found to be positive on Wood's lamp examination and/or Gram staining/culture were considered as erythrasma. RESULTS: The rate of erythrasma was found to be 46.7%. The mean age was 43.6 years, and the disease was more prevalent in men. The most common clinical finding was desquamation. Mycological examination was found as positive in 40.35% of the patients. No growth was observed in bacteriological cultures. It was found that using only Wood's lamp examination or Gram staining resulted in 11 (9%) and 19 positive patients (15.6%), respectively, whereas using both Wood's lamp examination and Gram staining concurrently resulted in 27 positive patients (22.1%). CONCLUSION: Interdigital erythrasma is a commonly seen condition and can clinically mimic tinea pedis. A Wood's lamp is a good diagnostic tool, but Gram staining, particularly in those with a negative Wood's lamp result, may be a useful method. PMID- 21977941 TI - Efficacy in asthma of once-daily treatment with fluticasone furoate: a randomized, placebo-controlled trial. AB - BACKGROUND: Fluticasone furoate (FF) is a novel long-acting inhaled corticosteroid (ICS). This double-blind, placebo-controlled randomized study evaluated the efficacy and safety of FF 200 mcg or 400 mcg once daily, either in the morning or in the evening, and FF 200 mcg twice daily (morning and evening), for 8 weeks in patients with persistent asthma. METHODS: Asthma patients maintained on ICS for >= 3 months with baseline morning forced expiratory volume in one second (FEV(1)) 50-80% of predicted normal value and FEV(1) reversibility of >= 12% and >= 200 ml were eligible. The primary endpoint was mean change from baseline FEV(1) at week 8 in pre-dose (morning or evening [depending on regimen], pre-rescue bronchodilator) FEV(1). RESULTS: A total of 545 patients received one of five FF treatment groups and 101 patients received placebo (intent-to-treat population). Each of the five FF treatment groups produced a statistically significant improvement in pre-dose FEV(1) compared with placebo (p < 0.05). FF 400 mcg once daily in the evening and FF 200 mcg twice daily produced similar placebo-adjusted improvements in evening pre-dose FEV(1) at week 8 (240 ml vs. 235 ml). FF 400 mcg once daily in the morning, although effective, resulted in a smaller improvement in morning pre-dose FEV(1) than FF 200 mcg twice daily at week 8 (315 ml vs. 202 ml). The incidence of oral candidiasis was low (0-4%) and UC excretion was comparable with placebo for all FF groups. CONCLUSIONS: FF at total daily doses of 200 mcg or 400 mcg was significantly more effective than placebo. FF 400 mcg once daily in the evening had similar efficacy to FF 200 mcg twice daily and all FF regimens had a safety tolerability profile generally similar to placebo. This indicates that inhaled FF is an effective and well tolerated once-daily treatment for mild-to-moderate asthma. TRIAL REGISTRATION: NCT00398645. PMID- 21977943 TI - Development of a tool to improve the quality of decision making in atrial fibrillation. AB - BACKGROUND: Decision-making about appropriate therapy to reduce the stroke risk associated with non-valvular atrial fibrillation (NVAF) involves the consideration of trade-offs among the benefits, risks, and inconveniences of different treatment options. The objective of this paper is to describe the development of a decision support tool for NVAF based on the provision of individualized risk estimates for stroke and bleeding and on preparing patients to communicate with their physicians about their values and potential treatment options. METHODS: We developed a tool based on the principles of the International Patient Decision Aids Standards. The tool focuses on the patient physician dyad as the decision-making unit and emphasizes improving the interaction between the two. It is built on the recognition that the application of patient values to a specific treatment decision is complex and that the final treatment choice is best made through a process of patient-clinician communication. RESULTS: The tool provides education incorporating patients ' illness perceptions to explain the relationship between NVAF and stroke, and then presents individualized risk estimates, derived using separate risk calculators for stroke and bleeding over a clinically meaningful time period (5 years) associated with no treatment, aspirin, and warfarin. Sequelae of both stroke and bleeding outcomes are also described. Patients are encouraged to verbalize how they value the incremental risks and benefits associated with each option and write down specific concerns to address with their physician. A physician prompt to encourage patients to discuss their opinions is included as part of the decision support tool. In pilot testing with 11 participants (mean age 78 +/- 9 years, 64% with <= high-school education), 8 (72%) rated ease of completion as "very easy," and 9 (81%) rated amount of information as "just right." CONCLUSIONS: The risks and benefits of different treatment options for reduction of stroke in NVAF vary widely according to patients' comorbidities. This tool facilitates the provision of individualized outcome data and encourages patients to communicate with their physicians about these risks and benefits. Future studies will examine whether use of the tool is associated with improved quality of decision making. PMID- 21977945 TI - Metformin-associated lactic acidosis following acute kidney injury. Efficacious treatment with continuous renal replacement therapy. AB - INTRODUCTION: Metformin is a biguanide anti-hyperglycaemic drug. Metformin associated lactic acidosis may sometimes be life-threatening. Continuous renal replacement therapy has been suggested as a method for resolving this extremely dangerous metabolic state. We describe the history of six patients admitted to the intensive care unit over a 28-month period in pre-shock conditions because of severe lactic acidosis, attributed to metformin-associated lactic acidosis, and successfully treated. METHODS: We reviewed the charts of six patients admitted to our intensive care unit between January 2008 and May 2010. After initial assessment, all patients were treated with continuous renal replacement therapy. Admission serum lactate and creatinine levels, pH, need for ventilatory and cardiovascular support, as well as continuous renal replacement therapy details and length of stay were reviewed. RESULTS: Admission pH levels of the six patients ranged between pH 6.63 and 7.0 and their serum lactate levels ranged between 12 and 27 mmol/l; the estimated creatinine clearance ranged between 6 and 24 ml min(-1) 1.73 m(-2) . All patients required vasoactive support and five required ventilatory support. Lactate levels decreased to near zero with continuous renal replacement therapy within 7-19 h in five of the patients whose intensive care unit length of stay ranged between 1 and 5 days. One patient's length of stay reached 11 days because of pneumonia, one died from multi-organ failure and another suffered permanent neurological damage following prolonged cardiopulmonary resuscitation before continuous renal replacement therapy was administered. All other patients recovered without sequellae. CONCLUSIONS: Accurate recognition of metformin-associated lactic acidosis and prompt initiation of haemodialysis are paramount steps towards rapid recovery. Large series reports and controlled studies may better determine the optimal duration and best dialysis technique in these patients. PMID- 21977944 TI - Increased intestinal permeability and tight junction disruption by altered expression and localization of occludin in a murine graft versus host disease model. AB - BACKGROUND: Hematopoietic stem cell transplantation is increasingly performed for hematologic diseases. As a major side effect, acute graft versus host disease (GvHD) with serious gastrointestinal symptoms including diarrhea, gastrointestinal bleeding and high mortality can be observed. Because surveillance and biopsies of human gastrointestinal GvHD are difficult to perform, rare information of the alterations of the gastrointestinal barrier exists resulting in a need for systematic animal models. METHODS: To investigate the effects of GvHD on the intestinal barrier of the small intestine we utilized an established acute semi allogenic GvHD in C57BL/6 and B6D2F1 mice. RESULTS: By assessing the differential uptake of lactulose and mannitol in the jejunum, we observed an increased paracellular permeability as a likely mechanism for disturbed intestinal barrier function. Electron microscopy, immunohistochemistry and PCR analysis indicated profound changes of the tight-junction complex, characterized by downregulation of the tight junction protein occludin without any changes in ZO-1. Furthermore TNF-alpha expression was significantly upregulated. CONCLUSIONS: This analysis in a murine model of GvHD of the small intestine demonstrates serious impairment of intestinal barrier function in the jejunum, with an increased permeability and morphological changes through downregulation and localization shift of the tight junction protein occludin. PMID- 21977946 TI - The role of asynapsis in human spermatocyte failure. AB - The basic molecular mechanisms by which chromosomal rearrangements in heterozygous state produce spermatogenic disturbances are poorly understood. Testicular biopsies from five patients - one carrier of a Robertsonian translocation rob t(13;14), two carriers of two different Y-autosome translocations, a t(Y;6) and a t(Y;11), one carrier of a reciprocal translocation t(3;13) and one carrier of a heterochromatin duplication in chromosome 9 - were processed for histopathological analysis, electron microscopy and fluorescent immunolocalization of meiotic proteins. In all the patients, the asynaptic regions during pachytene are labelled by BRCA1 and retained RAD51 foci. The variant histone gamma-H2AX is located on the chromatin domains of the asynaptic regions and the XY body. In contrast, these meiotic proteins are absent in those chromosomal segments that are non-homologously synapsed. The present observations on five new cases and a review of recent studies show that the common features shared by all these cases are the abnormal location of some meiotic proteins and the presence of transcriptionally silenced chromatin domains on asynaptic regions. The frequent association of these silenced regions with the XY body and the rescue of spermatocyte viability through non-homologous synapsis are also shared by all these carriers. A passive, random mechanism of clustering of asynaptic regions with the XY body is suggested. PMID- 21977947 TI - Distribution of CYP2C polymorphisms in an Amerindian population of Brazil. PMID- 21977948 TI - Vasoactive properties of keratin-derived compounds. AB - OBJECTIVE: Keratin proteins have been utilized as biomaterials for decades, and are currently under investigation for a variety of tissue regeneration and trauma applications. It has been suggested that certain keratins may have the capacity to act as a colloid in fluid resuscitation applications, providing viscosity and oncotic properties that may be beneficial during acute ischemic events. Oxidized keratin derivatives, also known as keratoses, show good blood and cardiovascular compatibility and thus are the subject of this study. METHODS: The effects of keratose compounds will be assessed using a topload i.v. infusion model and observation of changes in the microvasculature of the cremaster muscle of rats. RESULTS: Keratose resuscitation fluid (KRF) administration resulted in significant vasodilation in the cremaster muscle. This effect was blocked with pretreatment of l-NA to inhibit NO. Another keratin fraction, alpha-keratose, which is the primary viscosic compound, was not found to induce vasodilation. CONCLUSIONS: The apparent mechanism of vasodilation was found to be NO-mediated and isolated to a particular purified fraction, the KAP. PMID- 21977950 TI - Turbo tips. PMID- 21977949 TI - Introducing the concept of pragmatic esthetics, with special reference to the treatment of tooth wear. PMID- 21977951 TI - Enameloplasty and esthetic finishing in orthodontics-identification and treatment of microesthetic features in orthodontics part 1. AB - Interdisciplinary treatment also has expanded to include not only soft tissue assessment of the periodontal components of the dentition and smile, but of the face as well. The next level of esthetic enhancement certainly will include facial proportionality as a key component in our patient evaluation. This paper expands the diagnostic vision of the dentist to include facial proportions and relationships of hard and soft tissues to improve diagnosis and treatment of dental and facial esthetics. PMID- 21977952 TI - Enameloplasty and esthetic finishing in orthodontics-differential diagnosis of incisor proclination-the importance of appropriate visualization and records part 2. AB - The purpose of this paper is to briefly review some of the principals of ideal tooth shape and morphology and demonstrate how to use tooth reshaping through enameloplasty to treat and finish orthodontic cases to much more esthetic conclusions. This paper demonstrates the significant improvement to a smile orthodontists can achieve if they understand the principles of dental esthetics. In assessing smile design, the patient must be evaluated in three dimensions, and both dental and skeletal components must be considered. Expanded documentation in the form of frontal, profile, and oblique images taken both at rest and on dynamic smile permits the dentist to evaluate these elements without cephalometric radiography. PMID- 21977953 TI - Commentary. Enameloplasty and esthetic finishing in orthodontics part 1 and part 2. PMID- 21977954 TI - Effects of various beverages on hardness, roughness, and solubility of esthetic restorative materials. AB - STATEMENT OF THE PROBLEM: Restorative materials may either be exposed intermittently or continuously to chemical agents found in beverages, which may lead to biodegradation. PURPOSE: This study was aimed to evaluate effects of various beverages on microhardness, surface roughness, and solubility of esthetic restorative materials. MATERIALS AND METHODS: Materials used were conventional glass ionomer, resin-modified glass ionomer, compomer, and composite resin. Microhardness of the restorative materials was measured using Vickers microhardness tester. Surface roughness was measured using surface profilometery. Solubility was measured using an electronic balance. RESULTS: In general, low pH beverages adversely affected the properties of the tested materials. Microhardness of tested materials was significantly decreased after immersion in the various beverages, whereas surface roughness and solubility were increased with the exception of natural milk. Natural milk and water did not affect the tested materials as Mirinda orange or mango juice did. Microhardness, roughness, and solubility of the tested materials in water were comparable with those of natural milk. After the immersion period, the conventional glass ionomer showed the roughest surface and exhibited the highest solubility, whereas composite resin was the smoothest surface and the lowest solubility. There was a negative correlation between surface roughness and microhardness, as well as between solubility and microhardness. There was a positive correlation between surface roughness and solubility. CONCLUSIONS: Low pH beverages were the most aggressive media for glass ionomers and compomer, by contrast, composite resin was relatively less affected. Water and natural milk appeared relatively benign towards the tested materials. PMID- 21977955 TI - Commentary. Effects of various beverages on hardness, roughness, and solubility of esthetic restorative materials. PMID- 21977956 TI - Silorane-based composite: depth of cure, surface hardness, degree of conversion, and cervical microleakage in Class II cavities. AB - OBJECTIVE: The purpose of this study was to determine the depth of cure, degree of conversion (DC), hardness, and cervical sealing ability of silorane-based composite (Filtek Silorane [FS; 3M, Seefeld, Germany]) and to compare with methacrylate-based composites (MBCs = Filtek Supreme XT [FSXT] and Filtek P60 [FP60]). MATERIALS AND METHODS: The DC and hardness of every material were evaluated after 1, 7, and 30 days. The depth of cure was determined using the ISO 4049:2000 standard. Microleakage was evaluated by measuring dye penetration across the gingival wall in cross-sectioned specimens. RESULTS: FS showed lower depth of cure than FSXT and FP60. The DC of FS was significantly lower when compared to FP60 and FSXT. FS exhibited lower hardness than both FSXT and FP60 after 1 day of storage. The hardness of FS remained unchanged during the storage period. FS showed reduced microleakage scores compared to FSXT and showed similar microleakage scores compared to FP60. CONCLUSIONS: In conclusion, the DC and cure depth of FS are lower than those of MBCs. However, FS revealed stable hardness in water that is comparable to MBCs. The sealing ability of FS is similar or even better than that of MBCs. PMID- 21977957 TI - Commentary. Silorane-based composite: depth of cure, surface hardness, degree of conversion, and cervical microleakage in class II cavities. PMID- 21977958 TI - Effect of whitening dentifrices on the surface roughness of commercial composites. AB - PURPOSE: Our study aimed to test the null hypothesis that whitening and non whitening dentifrices affect similarly the surface roughness of commercial microhybrid composites, independent of the brushing time. MATERIALS AND METHODS: One hundred and ninety-two disc-shaped specimens of Filtek Z250 (3 M/ESPE, St. Paul, MN, USA) and Rok (SDI, Australia) were built up and randomly assigned to 24 groups, based on the dentifrices used (two whitening dentifrices: Colgate Max White-Colgate-Palmolive, Sao Bernardo do Campo, Sao Paulo, Brazil and Close Up Extra Whitening-Unilever, Brasil Higiene Pessoal e Limpeza Ltda, Ipojuca, Pernambuco, Brazil; and one non-whitening dentifrice: Colgate Total 12 Clean Mint Colgate-Palmolive), and on the simulated brushing times (24 hours, 6, 12 and 24 months). The specimens were submitted to the toothbrushing regimens after which the surface roughness (Ra) was measured. Data was submitted to analysis of variance and Tukey test (alpha=0.05). RESULTS: The composite's surface roughness was significantly affected by the composites (p=0.0007), the dentifrices (p=0.0001), and the simulated brushing time (p=0.0001). Higher roughness was observed when the whitening dentifrices were used and when the brushing time increased. Filtek Z250 was more affected than Rok, especially after 24 months of simulated brushing. CONCLUSION: Whitening dentifrices produced higher surface roughness in the composites tested. The degree of surface compromising increased with brushing time and depends on the composite's microstructure and composition. PMID- 21977959 TI - Commentary. Effect of whitening dentifrices on the surface roughness of commercial composites. PMID- 21977960 TI - Critical appraisal. Dentin bonding: matrix metalloproteinases and chlorhexidine. AB - Contemporary resin-dentin bonding is initiated by systems that use phosphoric acid or acidic resin monomers to remove mineral, exposing the superficial dentin collagen matrix. Collagen-associated proteins, including enzymes known as matrix metalloproteinases (MMPs), also are exposed. The collagen matrix is subsequently infiltrated with resins that are polymerized to establish an adhesive attachment to the dentin. Exposed collagen matrix that is not infiltrated with the adhesive can be degraded by associated MMPs, which might result in deterioration of the adhesive-dentin bond over time. Chlorhexidine (CHX) is able to inhibit MMPs by binding calcium and zinc ions necessary for proteolytic activity. This Critical Appraisal presents salient publications on research that evaluate CHX and its ability to limit MMP degradation of dentin bonds created by etch-and-rinse and self-etch adhesive systems. PMID- 21977961 TI - Affective imagery and acceptance of replacing nuclear power plants. AB - This study examined the relationship between the content of spontaneous associations with nuclear power plants and the acceptance of using new-generation nuclear power plants to replace old ones. The study also considered gender as a variable. A representative sample of the German- and French-speaking population of Switzerland (N= 1,221) was used. Log-linear models revealed significant two way interactions between the association content and acceptance, association content and gender, and gender and acceptance. Correspondence analysis revealed that participants who were opposed to nuclear power plants mainly associated nuclear power plants with risk, negative feelings, accidents, radioactivity, waste disposal, military use, and negative consequences for health and environment; whereas participants favoring nuclear power plants mainly associated them with energy, appearance descriptions of nuclear power plants, and necessity. Thus, individuals opposing nuclear power plants had both more concrete and more diverse associations with them than people who were in favor of nuclear power plants. In addition, participants who were undecided often mentioned similar associations to those participants who were in favor. Males more often expressed associations with energy, waste disposal, and negative health effects. Females more often made associations with appearance descriptions, negative feelings, and negative environmental effects. The results further suggest that acceptance of replacing nuclear power plants was higher in the German-speaking part of the country, where all of the Swiss nuclear power plants are physically located. Practical implications for risk communication are discussed. PMID- 21977962 TI - Using mesoscopic models to design strong and tough biomimetic polymer networks. AB - Using computational modeling, we investigate the mechanical properties of polymeric materials composed of coiled chains, or "globules", which encompass a folded secondary structure and are cross-linked by labile bonds to form a macroscopic network. In the presence of an applied force, the globules can unfold into linear chains and thereby dissipate energy as the network is deformed; the latter attribute can contribute to the toughness of the material. Our goal is to determine how to tailor the labile intra- and intermolecular bonds within the network to produce material exhibiting both toughness and strength. Herein, we use the lattice spring model (LSM) to simulate the globules and the cross-linked network. We also utilize our modified Hierarchical Bell model (MHBM) to simulate the rupture and reforming of N parallel bonds. By applying a tensile deformation, we demonstrate that the mechanical properties of the system are sensitive to the values of N(in) and N(out), the respective values of N for the intra- and intermolecular bonds. We find that the strength of the material is mainly controlled by the value of N(out), with the higher value of N(out) providing a stronger material. We also find that, if N(in) is smaller than N(out), the globules can unfold under the tensile load before the sample fractures and, in this manner, can increase the ductility of the sample. Our results provide effective strategies for exploiting relatively weak, labile interactions (e.g., hydrogen bonding or the thiol/disulfide exchange reaction) in both the intra- and intermolecular bonds to tailor the macroscopic performance of the materials. PMID- 21977963 TI - Orbital emphysema following removal of bilateral midfacial implants. AB - A 36-year-old man with Crouzon syndrome was referred post-operatively with unilateral painful limitation of eye movements and proptosis following removal of bilateral malar and orbital rim implants. Further investigation revealed right inferior orbital emphysema, caused by the intra-operative entrance of hydrogen peroxide through a suspected perforation of the orbital septum. The symptoms settled with conservative management. PMID- 21977964 TI - Pyridin-2-yl guanidine derivatives: conformational control induced by intramolecular hydrogen-bonding interactions. AB - The synthesis and conformational analysis of a series of pyridin-2-yl guanidine derivatives using NMR, X-ray crystallography, and B3LYP/6-31+G** theoretical studies are reported. A remarkable difference was observed in the (1)H NMR spectra of the guanidinium salts as compared with their N,N'-di-Boc protected and neutral analogues. This difference corresponds to a 180 degrees change in the dihedral angle between the guanidine/ium moiety and the pyridine ring in the salts as compared to the Boc-protected derivatives, a conclusion that was supported by theoretical studies, X-ray data, and NMR analysis. Moreover, our data sustain the existence of two intramolecular hydrogen-bonding systems: (i) between the pyridine N1 atom and the guanidinium protons in the salts and (ii) within the tert-butyl carbamate groups of the Boc-protected derivatives. To verify that the observed conformational control arises from these intramolecular interactions, a new series of N-Boc-N'-propyl-substituted pyridin-2-yl guanidines were also prepared and studied. PMID- 21977965 TI - Long-term treatment with the dipeptidyl peptidase-4 inhibitor saxagliptin in patients with type 2 diabetes mellitus and renal impairment: a randomised controlled 52-week efficacy and safety study. AB - OBJECTIVE: Therapeutic options are limited for diabetes patients with renal disease. This report presents 52-week results from a study assessing the dipeptidyl peptidase-4 inhibitor saxagliptin in patients with type 2 diabetes mellitus (T2DM) and renal impairment. DESIGN: Double-blind study in patients stratified by baseline renal impairment (moderate, severe or end-stage renal disease [ESRD] on haemodialysis) randomised to saxagliptin 2.5 mg once daily or placebo added to other antidiabetic drugs in use at baseline, including insulin. PATIENTS: A total of 170 adults with glycated haemoglobin (HbA(1c) ) 7-11% and creatinine clearance < 50 ml/min or ESRD were randomised and treated. MEASUREMENTS: Absolute changes in HbA(1c) and fasting plasma glucose (FPG) from baseline to week 52 were evaluated using analysis of covariance (ANCOVA) with last observation carried forward. Repeated-measures analyses were also performed. RESULTS: Adjusted mean decrease in HbA(1c) was greater with saxagliptin than placebo (difference, -0.73%, p < 0.001 [ANCOVA]). Reductions in adjusted mean HbA(1c) were numerically greater with saxagliptin than placebo in patients with renal impairment rated as moderate (-0.94% vs. 0.19% respectively) or severe ( 0.81% vs. -0.49%), but similar to placebo for those with ESRD (-1.13% vs. 0.99%). Reductions in adjusted mean FPG were numerically greater with saxagliptin in patients with moderate or severe renal impairment. Saxagliptin was generally well tolerated; similar proportions of patients in the saxagliptin and placebo groups reported hypoglycaemic events (28% and 29% respectively). CONCLUSIONS: Saxagliptin 2.5 mg once daily offers sustained efficacy and good tolerability for patients with T2DM and renal impairment. PMID- 21977966 TI - Population intervention causal effects based on stochastic interventions. AB - Estimating the causal effect of an intervention on a population typically involves defining parameters in a nonparametric structural equation model (Pearl, 2000, Causality: Models, Reasoning, and Inference) in which the treatment or exposure is deterministically assigned in a static or dynamic way. We define a new causal parameter that takes into account the fact that intervention policies can result in stochastically assigned exposures. The statistical parameter that identifies the causal parameter of interest is established. Inverse probability of treatment weighting (IPTW), augmented IPTW (A-IPTW), and targeted maximum likelihood estimators (TMLE) are developed. A simulation study is performed to demonstrate the properties of these estimators, which include the double robustness of the A-IPTW and the TMLE. An application example using physical activity data is presented. PMID- 21977967 TI - Conformation, defects, and dynamics of a discotic liquid crystal and their influence on charge transport. AB - Future applications of discotic liquid crystals (DLCs) in electronic devices depend on a marked improvement of their conductivity properties. We present a study of 2,3,6,7,10,11-hexakishexyloxytriphenylene (HAT6) and show how local conformation, structural defects, and thermal motions on the picosecond time scale strongly affect the efficient charge transport in DLCs. A direct and successful comparison of classical molecular dynamics (MD) simulations with both neutron powder diffraction and quasielastic neutron scattering (QENS) give a full insight into the structural and dynamical properties of HAT6. The local conformation of HAT6 molecules is characterized by a mutual rotation (twist) angle of about 37 degrees and typically a mutual aromatic-core distance of 3.4 A instead of the average distance of 3.65 A usually quoted. We show that a considerable number of structural traps is present in HAT6, which persist at the picosecond time scale. We find that the high disorder in the mutual positions of the aromatic cores is an important factor contributing to the limited conductivity of HAT6 compared to larger DLCs. PMID- 21977968 TI - The rate of sex chromosome aneuploidies in prenatal diagnosis and subsequent decisions in Western Turkey. AB - AIMS: Sex chromosome abnormalities (SCAs) are the most common genetic disorder with a frequency of 1/400 or 1/500 live births. In this study we aimed to evaluate the initial indications, frequencies, and pregnancy termination rates of pregnancies with SCAs referred to Ege University Medical Faculty, Department of Medical Genetics. Prenatal diagnosis was performed in 7505 cases in the period of January 1998 through December 2009. RESULTS: In this study, their initial indications and fetal karyotype results were evaluated retrospectively. A total of 60 pregnancies (0.80%) with SCA were evaluated. Turner syndrome was the most commonly diagnosed SCA in prenatal diagnosis (60%). The most common referral reason for pregnancies with Turner syndrome was cystic hygroma on ultrasonography. Of 14 pregnancies having a prenatal diagnosis with SCA (Turner syndrome: 7, Klinefelter syndrome: 5, Mosaic Turner syndrome: 2), 12 with SCA (85.7%) were terminated. The ratio of SCA in the prenatally diagnosed cases was similar to those reported in the literature. Although the ratio of terminated pregnancies with Turner syndrome was similar to those reported from European countries, all the pregnancies with Klinefelter syndrome have chosen termination, which showed a regional difference in Turkey. CONCLUSION: It is important to consider the decisions of the families during the genetic counseling sessions of the couples having SCAs. PMID- 21977969 TI - Genetic polymorphism of estrogen metabolizing enzymes in Siberian women with breast cancer. AB - Allelic variants of cytochrome P450: CYP1A1, CYP1A2, CYP19 (aromatase), and the II-phase enzyme sulfotransferase 1A1 (SULT1A1) genes are associated with a high risk of hormone-dependent cancers. We estimated the frequency of these allelic variants in the female population of the Novosibirsk district and their association with the elevated risk of breast cancer. A DNA bank of patients with gynecologic oncology, patients with breast cancer (n = 335), and healthy women (n = 530) was created, and the following single-nucleotide polymorphisms were examined: CYP1A1 M1 polymorphism, that is, T264-C transition in the 30-noncoding region; CYP1A2*1F polymorphism, that is, C734-A transversion in the CYP1A2 gene; C-T transition (Arg264Cys) in exon 7 of CYP19; and SULT1A1*2 polymorphism, that is, G638-A transition (Arg213His) in the SULT1A1 gene. The results of our study indicate that women with mutant allele C and genotypes C/T, C/C of the CYP1A1 gene, wild-allele C, and genotype C/C of the CYP1A2 gene, mutant allele A and genotypes A/G, A/A of the SULT1A1 gene have an increased risk of development of breast cancer. Women with body mass index >= 30 and the heterozygous genotype C/T of the CYP19 gene have an increased risk of breast cancer. The CYP1A2 heterozygous variant genotype C/A is associated with an increased risk of an estrogen receptor (ER(+)) tumor. PMID- 21977970 TI - Serotonin receptor 2A -1438G/A promoter polymorphism in relation to obesity and response to sibutramine. AB - AIMS: Serotonin has been related to appetite and body weight control. The aim of this study was to investigate a possible association of the -1438 /A promoter polymorphism of the serotonin 2A receptor (5HT2AR) gene with obesity-related variables and response to sibutramine. PATIENTS/METHODS: We examined the potential impact of this polymorphism on obesity and related metabolic traits in a cohort of 234 overweight/obese and 103 lean Greek subjects. Additionally, we examined whether the 5HT2AR 1438A/G polymorphism influences weight reduction and change in body composition among 106 out of these subjects, who were treated with 15 g sibutramine. Genotyping was carried out by polymerase chain reaction and restriction enzyme analysis. RESULTS: Body mass index, fat mass, and waist circumference were not significantly different across the 5HT2AR 1438A/G genotype groups in overweight/obese women. Polymorphic G allele was associated with higher triglyceride and insulin levels but not with other biochemical and metabolic parameters. Distribution of genotypes and alleles was not different between responders and nonresponders (weight loss >5 or <5 g). CONCLUSIONS: Based on these results, it seems unlikely that the 5HT2AR 1438 /A polymorphism has a major impact on obesity and related traits or the response to sibutramine in Greek overweight/obese subjects. PMID- 21977971 TI - IgG4-related systemic disease--a rare indication for multi-visceral transplantation. AB - Multivisceral transplantations (MVT) are rarely performed procedures. In this case report, we present a 37-year-old male patient with a large retroperitoneal tumor. After exclusion of malignancy, we performed MVT (distal stomach, liver, pancreas, and small bowel). After a follow-up of 1 year, the patient is in good clinical condition. Histologic examination revealed a chronic sclerosing IgG4 associated disease. Our case shows that MVT can be successfully performed in this rare disease. PMID- 21977972 TI - Temporal and spatial regulation of microRNA activity with photoactivatable cantimirs. AB - MicroRNAs (miRNAs) are small non-coding RNAs that play numerous important roles in physiology and human diseases. During animal development, many miRNAs are expressed continuously from early embryos throughout adults, yet it is unclear whether these miRNAs are actually required at all the stages of development. Current techniques of manipulating microRNA function lack the required spatial and temporal resolution to adequately address the functionality of a given microRNA at a specific time or at single-cell resolution. To examine stage- or cell-specific function of miRNA during development and to achieve precise control of miRNA activity, we have developed photoactivatable antisense oligonucleotides against miRNAs. These caged oligonucleotides can be activated with 365 nm light with extraordinarily high efficiency to release potent antisense reagents to inhibit miRNAs. Initial application of these caged antimirs in a model organism (C. elegans) revealed that the activity of a miRNA (lsy-6) is required specifically around the comma stage during embryonic development to control a left/right asymmetric differentiation program in the C. elegans nervous system. This suggests that a transient input of lsy-6 during development is sufficient to specify the neuronal cell fate. PMID- 21977973 TI - Effectiveness of multiple release sites in reintroduction of Persian fallow deer. AB - Releasing animals in more than one location may increase or decrease the probability of success of a reintroduction project, yet the question of how many release sites to use has received little attention. We used empirical data from the reintroduction program of the Persian fallow deer (Dama mesopotamica) (Galilee region in northern Israel) in an individual-based spatially explicit simulation model to assess the effects of releasing deer from multiple sites. We examined whether multiple release sites increase reintroduction success, and if so, whether the optimal number of sites for a given scenario can be determined and whether the outcome differs if animals are released alternately (i.e., the location of the release alternates yearly between sites) or consecutively (i.e., one release site is used for several years, then another is used, and so forth). We selected 8 potential release sites in addition to the original site and simulated the release of 180 individuals at a rate of 10 individuals per year in different combinations of the original site and 1-4 additional sites. In our model, releasing animals into the wild at multiple sites produced higher population growth and greater spatial expansion than releasing animals at only one site and a consecutive-release approach was superior to an alternate-release approach. We suggest that through the use of simulation modeling that is based on empirical data from previous releases, managers can make better-informed decisions regarding the use of multiple release sites and greatly improve the probability of reintroduction success. PMID- 21977974 TI - Effects of pioglitazone add-on to gliclazide and metformin on glycemic control in patients with type 2 diabetes. AB - OBJECTIVES: This study aims to evaluate the efficacy and safety of adding pioglitazone to treatment with metformin (MF) and gliclazide in patients with type 2 diabetes mellitus (DM2) who had inadequate glycemic control. METHODS: This study is a retrospective cohort study based on King Abdullah University Hospital records concerning type 2 diabetic adult patients for year 2008. Patients included were assessed according to changes in glycosylated hemoglobin (HbA1c), lipid profile, albuminuria and liver enzymes before and after the addition of pioglitazone. RESULTS: The patients included in the study had an initial mean HbA1c of 9.44%, which decreased to 7.56% after the addition of pioglitazone (P value < 0.005). PMID- 21977976 TI - Luminescent copper(I) halide adducts of [Au(im(CH2py)2)2]PF6 exhibiting short Au(I)...Cu(I) separations and unusual semibridging NHC ligands. AB - The picolyl-substituted NHC complex [Au(im(CH(2)py)(2))(2)]PF(6) (1) reacts with two equivalents of copper(I) halides, affording compounds [Au(im(CH(2)py)(2))(2)(CuX)(2)]PF(6) (X = Cl, 2; Br, 3; I, 4). Each complex contains a nearly linearly coordinated [Au(NHC)(2)](+) center where the two picolyl groups on each im(CH(2)py)(2) ligand chelate a single copper atom. The Cu(I) center resides in a distorted tetrahedral environment and is coordinated to two pyridyl groups, a halide ion, and a gold metalloligand. The Au(I)-Cu(I) separations measure 2.7030(5), 2.6688(9), and 2.6786(10) A for 2-4, respectively. Additionally, each Cu(I) center is further coordinated by a semibridging NHC ligand with short Cu-C separations of ~2.3 A. In solution, these complexes dissociate the Cu(I) ion. In the solid state, 2-4 are photoluminescent with respective emission maxima of 512, 502, and 507 nm. The reaction of [Au(im(CH(2)py)(2))(2)]PF(6) with four equivalents of CuBr afforded the coordination polymer {[AuCu(2)Br(2)(im(CH(2)py)(2))(2)]Br.3CH(3)CN}(n) (5). This polymeric complex contains [Au(NHC)(2)](+) units interconnected by Cu(2)Br(2) dimers. In 5, the Au-Cu separations are long at 4.23 and 4.79 A, while the Cu-Cu distance is considerably shorter at 2.9248(14) A. In the solid state, 5 is photoluminescent with a broad band appearing at 533 nm. PMID- 21977977 TI - Facilitated transfer of IscU-[2Fe2S] clusters by chaperone-mediated ligand exchange. AB - The scaffold protein IscU and molecular chaperones HscA and HscB play central roles in biological assembly of iron-sulfur clusters and maturation of iron sulfur proteins. However, the structure of IscU-FeS complexes and the molecular mechanism whereby the chaperones facilitate cluster transfer to acceptor proteins are not well understood. We have prepared amino acid substitution mutants of Escherichia coli IscU in which potential ligands to the FeS cluster (Cys-37, Cys 63, His-105, and Cys-106) were individually replaced with alanine. The properties of the IscU-FeS complexes formed were investigated by measuring both their ability to transfer preformed FeS clusters to apo-ferredoxin and the activity of the IscU proteins in catalyzing cluster assembly on apo-ferredoxin using inorganic iron with inorganic sulfide or with IscS and cysteine as a sulfur source. The ability of the HscA/HscB chaperone system to accelerate ATP-dependent cluster transfer from each IscU substitution mutant to apo-ferredoxin was also determined. All of the mutants formed FeS complexes with a stoichiometry similar to the wild-type holo-protein, i.e., IscU(2)[2Fe2S], raising the possibility that different cluster ligation states may occur during iron-sulfur protein maturation. Spectroscopic properties of the mutants and the kinetics of transfer of performed IscU-FeS clusters to apo-ferredoxin indicate that the most stable form of holo-IscU involves iron coordination by Cys-63 and Cys-106. Results of studies on the ability of mutants to catalyze formation of holo-ferredoxin using iron and different sulfur sources were consistent with proposed roles for Cys-63 and Cys-106 in FeS cluster binding and also indicated an essential role for Cys 106 in sulfide transfer to IscU from IscS. Measurements of the ability of the chaperones HscA and HscB to facilitate cluster transfer from holo-IscU to apo ferredoxin showed that only IscU(H105A) behaved similarly to wild-type IscU in exhibiting ATP-dependent stimulation of cluster transfer. IscU(C63A) and IscU(C106A) displayed elevated rates of cluster transfer in the +/-ATP whereas IscU(C37A) exhibited low rates of cluster transfer +/-ATP. In interpreting these findings, we propose that IscU(2)[2Fe2S] is able undergo structural isomerization to yield conformers having different cysteine residues bound to the cluster. On the basis of the crystal structure of HscA complexed with an IscU-derived peptide, we propose that the chaperone binds and stabilizes an isomer of IscU(2)[2Fe2S] in which the cluster is bound by cysteine residues 37 and 63 and that the [2Fe2S] cluster, being held less tightly than that coordinated by Cys-63 and Cys-106 in free IscU(2)[2Fe2S], is more readily transferred to acceptor proteins such as apo-ferredoxin. PMID- 21977978 TI - Skill development in an employment-training program for adolescents with disabilities. AB - PURPOSE: Relatively little is known about the first employment experiences and skill development of youth with disabilities. The purpose of this study is to explore the skills gained by adolescents with disabilities who have completed an employment-training program. METHODS: In-depth, qualitative semi-structured interviews were conducted with 18 adolescents with a physical and/or mobility related disability. The youth and their parents also completed a brief questionnaire about their experience in the program and we reviewed their self- and staff-assessments that were completed throughout the program. RESULTS: The findings highlight how adolescents with disabilities developed several practical, social and communication skills, and self-confidence over the course of an employment-training program. Despite personal gains, youth reported challenges in their post-program search for employment. CONCLUSIONS: Youth valued involvement in the workforce and perceived that through their participation they developed important life skills. PMID- 21977975 TI - Antimutator variants of DNA polymerases. AB - Evolution balances DNA replication speed and accuracy to optimize replicative fitness and genetic stability. There is no selective pressure to improve DNA replication fidelity beyond the background mutation rate from other sources, such as DNA damage. However, DNA polymerases remain amenable to amino acid substitutions that lower intrinsic error rates. Here, we review these 'antimutagenic' changes in DNA polymerases and discuss what they reveal about mechanisms of replication fidelity. Pioneering studies with bacteriophage T4 DNA polymerase (T4 Pol) established the paradigm that antimutator amino acid substitutions reduce replication errors by increasing proofreading efficiency at the expense of polymerase processivity. The discoveries of antimutator substitutions in proofreading-deficient 'mutator' derivatives of bacterial Pols I and III and yeast Pol delta suggest there must be additional antimutagenic mechanisms. Remarkably, many of the affected amino acid positions from Pol I, Pol III, and Pol delta are similar to the original T4 Pol substitutions. The locations of antimutator substitutions within DNA polymerase structures suggest that they may increase nucleotide selectivity and/or promote dissociation of primer termini from polymerases poised for misincorporation, leading to expulsion of incorrect nucleotides. If misincorporation occurs, enhanced primer dissociation from polymerase domains may improve proofreading in cis by an intrinsic exonuclease or in trans by alternate cellular proofreading activities. Together, these studies reveal that natural selection can readily restore replication error rates to sustainable levels following an adaptive mutator phenotype. PMID- 21977983 TI - "Quenchbodies": quench-based antibody probes that show antigen-dependent fluorescence. AB - Here, we describe a novel reagentless fluorescent biosensor strategy based on the antigen-dependent removal of a quenching effect on a fluorophore attached to antibody domains. Using a cell-free translation-mediated position-specific protein labeling system, we found that an antibody single chain variable region (scFv) that had been fluorolabeled at the N-terminal region showed a significant antigen-dependent fluorescence enhancement. Investigation of the enhancement mechanism by mutagenesis of the carboxytetramethylrhodamine (TAMRA)-labeled anti osteocalcin scFv showed that antigen-dependency was dependent on semiconserved tryptophan residues near the V(H)/V(L) interface. This suggested that the binding of the antigen led to the interruption of a quenching effect caused by the proximity of tryptophan residues to the linker-tagged fluorophore. Using TAMRA scFv, many targets including peptides, proteins, and haptens including morphine related drugs could be quantified. Similar or higher sensitivities to those observed in competitive ELISA were obtained, even in human plasma. Because of its versatility, this "quenchbody" is expected to have a range of applications, from in vitro diagnostics, to imaging of various targets in situ. PMID- 21977984 TI - Oxidative C-H homodimerization of phenylacetamides. AB - A range of secondary and tertiary phenylacetamides undergo oxidative homodimerization to afford biaryls. The reaction proceeds under palladium catalysis in the presence of a copper cocatalyst and oxygen and is most effective for electron-rich substrates. PMID- 21977985 TI - Telocytes are the common cell of origin of both PEComas and GISTs: an evidence supported hypothesis. AB - We advance the hypothesis that the telocyte might be the cell of origin of both PEComas (perivascular epithelioid cell tumours) and GISTs (gastro-intestinal and extra-gastrointestinal stromal tumours). The hypothesis is supported by data from the literature reporting that both PEComas and GISTs, as well as telocytes, share the expression of several markers. These data were supplemented by original immunohistochemical tests on selected series. Specifically: (1) Melanoma markers (Melan A, MiTF) typical of PEComas are expressed by a substantial fraction of GISTs. A fraction of GISTs was also found positive for CD63, a tetraspanin protein originally described in melanomas and marking exosomes. (2) c-KIT (CD117), proper of the vast majority of GISTs, can be expressed by PEComas (as well as by telocytes). (3) Markers described in telocytes (CD34, S-100, smooth muscle actin and vascular endothelial growth factor) have been reported as positive in cases of PEComas and GISTs. Telocytes show distinctive ultrastructural features with thin, extended, telopodes and are likely involved in inter-cellular signalling via paracrine secretion as well as by shed vesicles and exosomes. These cells have been described in many locations (cavitary and non cavitary organs) and might display potentialities of a wide spectrum of differentiation (and function). In conclusion we propose that telocytes could be the common cells of origin for both PEComas and GISTs. PMID- 21977986 TI - ProDiGe: Prioritization Of Disease Genes with multitask machine learning from positive and unlabeled examples. AB - BACKGROUND: Elucidating the genetic basis of human diseases is a central goal of genetics and molecular biology. While traditional linkage analysis and modern high-throughput techniques often provide long lists of tens or hundreds of disease gene candidates, the identification of disease genes among the candidates remains time-consuming and expensive. Efficient computational methods are therefore needed to prioritize genes within the list of candidates, by exploiting the wealth of information available about the genes in various databases. RESULTS: We propose ProDiGe, a novel algorithm for Prioritization of Disease Genes. ProDiGe implements a novel machine learning strategy based on learning from positive and unlabeled examples, which allows to integrate various sources of information about the genes, to share information about known disease genes across diseases, and to perform genome-wide searches for new disease genes. Experiments on real data show that ProDiGe outperforms state-of-the-art methods for the prioritization of genes in human diseases. CONCLUSIONS: ProDiGe implements a new machine learning paradigm for gene prioritization, which could help the identification of new disease genes. It is freely available at http://cbio.ensmp.fr/prodige. PMID- 21977987 TI - Replication of LDL GWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses. AB - BACKGROUND: The PHArmacogenetic study of Statins in the Elderly at risk (PHASE) is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER) that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER/PHASE project and second show that the PROSPER/PHASE study can be used to study pharmacogenetics in the elderly. METHODS: The genome wide association study (GWAS) was conducted using the Illumina 660K-Quad beadchips following manufacturer's instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification. RESULTS: Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE/APOC1; LDLR; FADS2/FEN1; HMGCR; PSRC1/CELSR5). The top SNP (rs445925, chromosome 19) with a p-value of p = 2.8e 30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19) with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results. CONCLUSION: With the GWAS in the PROSPER/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof-of-principle study we show that the PROSPER/PHASE study can be used to investigate genetic associations in a similar way to population based studies. The next step of the PROSPER/PHASE study is to identify the genetic variation responsible for the variation in LDL-cholesterol lowering in response to statin treatment in collaboration with other large trials. PMID- 21977988 TI - Is Roifman syndrome an X-linked ciliopathy with humoral immunodeficiency? Evidence from 2 new cases. AB - Roifman syndrome is a rare syndrome of bone dysplasia, growth retardation, retinal dystrophy and humeral immunodeficiency. Six cases have been reported to date, all of whom are male. We report a boy with clinical features of Roifman syndrome, whose older sister has skewed X-inactivation and a milder phenotype of the same disorder, supporting the hypothesis that this is an X-linked recessive condition. Both children had previously had a provisional diagnosis of Jeune dysplasia, and the boy had neonatal hip X-rays which demonstrated 'acetabular spurs' which are seen in a number of diseases thought to be caused by dysfunction of nonmotile cilia, including Jeune asphyxiating thoracic dystrophy. This finding in combination with other features such as retinal dystrophy, hepatic and renal disease suggests that the gene which is affected in Roifman syndrome may be involved with the function of nonmotile cilia and that Roifman syndrome may be the first example of a ciliopathy with associated immunodeficiency. PMID- 21977989 TI - Genotype and phenotype in Klinefelter syndrome - impact of androgen receptor polymorphism and skewed X inactivation. AB - The phenotypic variation of Klinefelter syndrome (KS) is wide and may by caused by various genetic and epigenetic effects. Skewed inactivation of the supra numerical X chromosome and polymorphism in the androgen receptor (AR) have been suggested as plausible causes. We wanted to describe X-chromosome inactivation patterns and the AR polymorphism and correlate these to clinical findings in KS in a cross-sectional study. To that end, we studied 70 KS patients enrolled from fertility clinics and endocrine clinics and 70 age-matched control subjects. The main outcome was X-chromosome inactivation pattern (skewX), AR polymorphism (CAGn - repeat length) and correlation to anthropometrical, hormonal, metabolic and bone-related variables. Forty-six of 70 KS men were heterozygous for CAGn. The shortest and the longest alleles were equally frequent inactivated and the mean CAGn of the two alleles did not differ significantly from the CAGn from either KS men, homozygous for the CAGn, or from the control subjects (22 vs. 23 vs. 21). SkewX was found in 12 of the 46 informative KS men (26%). In KS, height and arm span correlated positively to CAGn, whereas total cholesterol and haematocrit correlated negatively to CAGn. In controls, bone mineral density at the spine and hip correlated positively with CAGn, whereas adiponectin correlated negatively with CAGn. SkewX did not correlate to any of the investigated parameters. We conclude that CAGn polymorphism in AR explain some of the phenotypic variation in KS, whereas skewed X-chromosome inactivation did not. The impact of CAGn on final height may be caused by later reactivation of the pituitary-gonadal axis. PMID- 21977990 TI - Statistical software applications used in health services research: analysis of published studies in the U.S. AB - BACKGROUND: This study aims to identify the statistical software applications most commonly employed for data analysis in health services research (HSR) studies in the U.S. The study also examines the extent to which information describing the specific analytical software utilized is provided in published articles reporting on HSR studies. METHODS: Data were extracted from a sample of 1,139 articles (including 877 original research articles) published between 2007 and 2009 in three U.S. HSR journals, that were considered to be representative of the field based upon a set of selection criteria. Descriptive analyses were conducted to categorize patterns in statistical software usage in those articles. The data were stratified by calendar year to detect trends in software use over time. RESULTS: Only 61.0% of original research articles in prominent U.S. HSR journals identified the particular type of statistical software application used for data analysis. Stata and SAS were overwhelmingly the most commonly used software applications employed (in 46.0% and 42.6% of articles respectively). However, SAS use grew considerably during the study period compared to other applications. Stratification of the data revealed that the type of statistical software used varied considerably by whether authors were from the U.S. or from other countries. CONCLUSIONS: The findings highlight a need for HSR investigators to identify more consistently the specific analytical software used in their studies. Knowing that information can be important, because different software packages might produce varying results, owing to differences in the software's underlying estimation methods. PMID- 21977991 TI - High serum ferritin levels are associated with metabolic risk factors in non obese Korean young adults: Korean National Health and Nutrition Examination Survey (KNHANES) IV. AB - OBJECTIVE: The purpose of this study is to investigate the relationship between serum ferritin levels and metabolic risk factors in nonobese Korean young adults. DESIGN AND SUBJECTS: We analysed the fourth annual Korea National Health and Nutrition Examination Survey (KNHANES) in young adults (aged 19-39 years), conducted between 2007 and 2008. A total of 1542 nonobese [body mass index (BMI) <25 kg/m(2) ] young adults (684 men and 858 women) were enrolled. Using blood pressure and levels of serum triglycerides, plasma glucose and high-density lipoprotein (HDL) cholesterol, the Asian criteria for abdominal obesity (Waist circumference >=90 cm in men or >=80 cm in women) was used to identify individuals with metabolic syndrome. MEASUREMENTS: Data on anthropometry, fasting plasma glucose, insulin, lipid profile and ferritin levels were analysed. RESULTS: The prevalence of metabolic syndrome was 4.1% for men and 2.7% for women. High fasting glucose and the prevalence of metabolic syndrome increased progressively across three different tertiles of ferritin levels in men. However, high ferritin levels were associated with high triglycerides, low HDL cholesterol and metabolic syndrome in women. After adjustment for age, smoking, alcohol consumption, BMI and ALT levels, low HDL cholesterol (OR 1.66, 95% confidence interval (CI) 1.16-2.36) and the presence of metabolic syndrome (OR 3.87, 95% CI 1.34-11.2) were independently associated with high serum ferritin levels in Korean nonobese young women. CONCLUSIONS: Our results suggest that elevated serum ferritin levels may be employed as a marker of metabolic syndrome in nonobese young adult women. PMID- 21977992 TI - Formulation and in vitro assessment of sustained release terbutaline sulfate tablet made from binary hydrophilic polymer mixtures. AB - In the present systematic study, a sustained release of terbutaline sulfate tablet (TBS) was developed and optimized by employing the hydrophilic polymers; chitosan and xanthan gum mixed with sodium bicarbonate as a release modifying agent. This formulation was developed using direct compression technology. In vitro release studies indicated rapid swelling and drug release in the initial period of the acid stage from a matrix composed of chitosan and xanthan gum solely. Addition of sodium bicarbonate to the matrix resulted in sustained drug release. Various formulation factors such as polymer to polymer ratio, polymer viscosity and particle size were altered and their effect on dissolution pattern was illustrated. Manufacturing variables such as compression force and lubricant percentage were investigated and found not to influence the drug release profile of the resulted tablets. The release mechanism follows Korsmeyer-Peppas equation with n value indicating non-Fickian diffusion. The release profiles were analyzed using statistical method (one-way ANOVA) and f2 metric values and found to be similar to the commercial product Bricanyl((r)). Reproducible data were obtained when scale-up of the formulation was performed. PMID- 21977993 TI - Concerted vs stepwise mechanisms in dehydro-Diels-Alder reactions. AB - The Diels-Alder reaction is not limited to 1,3-dienes. Many cycloadditions of enynes and a smaller number of examples with 1,3-diynes have been reported. These "dehydro"-Diels-Alder cycloadditions are one class of dehydropericyclic reactions which have long been used to generate strained cyclic allenes and other novel structures. CCSD(T)//M05-2X computational results are reported for the cycloadditions of vinylacetylene and butadiyne with ethylene and acetylene. Both concerted and stepwise diradical routes have been explored for each reaction, with location of relevant stationary points. Relative to 1,3-dienes, replacement of one double bond by a triple bond adds 6-6.5 kcal/mol to the activation barrier; a second triple bond adds 4.3-4.5 kcal/mol to the barrier. Product strain decreases the predicted exothermicity. In every case, a concerted reaction is favored energetically. The difference between concerted and stepwise reactions is 5.2-6.6 kcal/mol for enynes but diminishes to 0.5-2 kcal/mol for diynes. Experimental studies on intramolecular diyne + ene cycloadditions show two distinct reaction pathways, providing evidence for competing concerted and stepwise mechanisms. Diyne + yne cycloadditions connect with arynes and ethynyl 1,3-cyclobutadiene. This potential energy surface appears to be flat, with only a minute advantage for a concerted process; many diyne cycloadditions or aryne cycloreversions will proceed by a stepwise mechanism. PMID- 21977994 TI - Helper T-cell differentiation and plasticity: insights from epigenetics. AB - CD4(+) T cells have critical roles in orchestrating immune responses to diverse microbial pathogens. This is accomplished through the differentiation of CD4(+) T helper cells to specialized subsets in response to microbial pathogens, which evoke a distinct cytokine milieu. Signal transducer and activator of transcription family transcription factors sense these cytokines and they in turn regulate expression of lineage-defining master regulators that programme selective gene expression, resulting in distinctive phenotypes. However, phenotype and restricted gene expression are determined not only by the action of transcription factors; chromatin accessibility is required for these factors to exert their effect. Technical advances have greatly expanded our understanding of transcription factor action and dynamic changes in the epigenome that accompany cellular differentiation. In this review, we will discuss recent progress in the understanding of how cytokines influence gene expression and epigenetic modifications, and the impact of these findings on our views of helper cell lineage commitment and plasticity. PMID- 21977995 TI - Mechanisms regulating chemokine receptor activity. AB - Co-ordinated movement and controlled positioning of leucocytes is key to the development, maintenance and proper functioning of the immune system. Chemokines and their receptors play an essential role in these events by mediating directed cell migration, often referred to as chemotaxis. The chemotactic property of these molecules is also thought to contribute to an array of pathologies where inappropriate recruitment of specific chemokine receptor-expressing leucocytes is observed, including cancer and inflammatory diseases. As a result, chemokine receptors have become major targets for therapeutic intervention, and during the past 15 years much research has been devoted to understanding the regulation of their biological activity. From these studies, processes which govern the availability of functional chemokine receptors at the cell surface have emerged as playing a central role. In this review, we summarize and discuss current knowledge on the molecular mechanisms contributing to the regulation of chemokine receptor surface expression, from gene transcription and protein degradation to post-translational modifications, multimerization, intracellular transport and cross-talk. PMID- 21977996 TI - Human and rhesus plasmacytoid dendritic cell and B-cell responses to Toll-like receptor stimulation. AB - Interferon-alpha (IFN-alpha) produced at high levels by human plasmacytoid dendritic cells (pDCs) can specifically regulate B-cell activation to Toll-like receptor (TLR) 7/8 stimulation. To explore the influence of IFN-alpha and pDCs on B-cell functions in vivo, studies in non-human primates that closely resemble humans in terms of TLR expression on different subsets of immune cells are valuable. Here, we performed a side-by side comparison of the response pattern between human and rhesus macaque B cells and pDCs in vitro to well-defined TLR ligands and tested whether IFN-alpha enhanced B-cell function comparably. We found that both human and rhesus B cells proliferated while pDCs from both species produced high levels of IFN-alpha in response to ligands targeting TLR7/8 and TLR9. Both human and rhesus B-cell proliferation to TLR7/8 ligand and CpG class C was significantly increased in the presence of IFN-alpha. Although both human and rhesus B cells produced IgM upon stimulation, only human B cells acquired high expression of CD27 associated with plasmablast formation. Instead, rhesus B-cell differentiation and IgM levels correlated to down-regulation of CD20. These data suggest that the response pattern of human and rhesus B cells and pDCs to TLR7/8 and TLR9 is similar, although some differences in the cell surface phenotype of the differentiating cells exist. A more thorough understanding of potential similarities and differences between human and rhesus cells and their response to potential vaccine components will provide important information for translating non-human primate studies into human trials. PMID- 21977997 TI - Transient modification within a pool of CD4 T cells in the maternal spleen. AB - Classic models suggest maternal tolerance is dependent on regulation of fetal antigen-specific T cell responses. We hypothesize that factors unique to a particular fetal antigen-specific T cell, rather than the state of pregnancy per se, are important determinants of T cell fate during pregnancy. To investigate the fate of fetal antigen-specific CD4 T cells in the systemic circulation, we examined spleen cells in a CD4 T cell receptor transgenic mouse specific for the male antigen H-Y. We observed a transient decrease in CD4(+) Vbeta6(+) cell numbers and, due to transient internalization of CD4, an increase in CD4(-) Vbeta6(+) T cells. Antigen-specific in vitro responsiveness was not depressed by pregnancy. These data suggest that pregnancy supports fluidity in this particular CD4 T cell pool that may, in turn, help to meet competing requirements of maternal immune responsiveness and fetal tolerance. PMID- 21977998 TI - Selective inhibition and augmentation of alternative macrophage activation by progesterone. AB - Progesterone is the female sex hormone necessary for the maintenance of pregnancy, and is known to modulate macrophage activation. However, studies have concentrated exclusively on the ability of progesterone to negatively regulate the innate and classical pathways of activation, associated with nitric oxide (NO) and interleukin (IL)-12 production. Our aim was to examine the ability of progesterone to modulate alternative macrophage activation. Bone marrow cells were isolated and differentiated from male BALB/c mice, exposed to varying concentrations of progesterone and stimulated with lipopolysaccharide (LPS) (innate activation), IL-4 (alternative activation) or LPS in combination with IL 4. Our present study demonstrates that progesterone not only down-regulates inducible nitric oxide synthase 2 (iNOS) activity in macrophages but also arginase activity, in a dose-dependent manner, independent of the stimuli, whether it is induced by LPS (innate activation), IL-4 (alternative activation) or LPS in combination with IL-4. The ability of progesterone to down-modulate IL 4-induced cell surface expression of the mannose receptor further suggested a negative regulation of alternative macrophage activation by this hormone. Analysis of mRNA expression, by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), of genes associated with innate and alternative macrophage activation revealed that progesterone down-regulated LPS-induced macrophage nos2, argI and p40 (IL-12/IL-23) expression and IL-4-induced argI, mrc 1 and fizz1 expression. However, progesterone up-regulated IL-4-induced macrophage expression of ym1, while dectin-1 expression remained unaltered. Following treatment of macrophages with LPS and IL-4 in combination a similar pattern was observed, with the exception that progesterone up-regulated macrophage expression of fizz1 as well as ym1 and did not modify mrc-1 expression. Our data demonstrate for the first time that a hormone has the ability to regulate selectively the expression of different genes associated with alternative macrophage activation. PMID- 21978000 TI - The expansion ability but not the quality of HIV-specific CD8(+) T cells is associated with protective human leucocyte antigen class I alleles in long-term non-progressors. AB - Studies in long-term non-progressors (LTNP) have suggested that the quality of the CD8(+) response may involve protective human leucocyte antigen (HLA) class I alleles. However, studies examining the expansion ability of different functional CD8(+) T cells and their association with HLA class I alleles are lacking. LTNP, untreated typical progressors (TP) and patients successfully on highly active retroviral therapy (HAART) during 1 year (HP) were included. HLA class I typing was performed using a sequence-specific primer assay. Functional subsets of Gag- and Nef-specific CD8(+) cells were analysed based on the production of macrophage inflammatory protein (MIP)-1beta, tumour necrosis factor (TNF)-alpha and interleukin (IL)-2. Their expansion abilities were evaluated after 10-day culture in the presence of Gag and Nef human immunodeficiency virus (HIV) peptides. No differences were seen when comparing quantitative and qualitative HIV-specific CD8(+) T cell responses according to the presence/absence of protective HLA alleles (B*58 and B*27 supertypes) in each group. However, LTNP with protective HLA alleles showed a higher expansion ability of Gag-specific MIP(+) TNF(+) IL 2(+) T cells and Nef-specific MIP(+) TNF(+) IL-2(+) . HLA-B*5701+LTNP displayed a higher expansion ability of Gag and Nef-specific MIP(+) TNF(-) IL-2(+) T cells than HLA-B*5701-LTNP. This was not so for HLA-B*2705. No differences were seen in the expansion ability according to the presence/absence of protective HLA alleles in TP and HP. The expansion ability of polyfunctional CD8(+) T cells is modulated by HLA class I alleles and targeted protein. LTNP with HLA class I protective alleles (mainly B*5701) display better expansion ability of polyfunctional HIV specific CD8(+) T cells than the rest, suggesting that factors other than HLA B*5701 must contribute to the control of viral replication in other LTNP. Furthermore, these attributes of HIV-specific CD8(+) T are not restored by HAART; thus, adjuvant therapies and vaccines that induce and/or normalize the expansion ability of HIV-specific T cells are required. PMID- 21977999 TI - Equine CD4(+) CD25(high) T cells exhibit regulatory activity by close contact and cytokine-dependent mechanisms in vitro. AB - Horses are particularly prone to allergic and autoimmune diseases, but little information about equine regulatory T cells (Treg) is currently available. The aim of this study therefore was to investigate the existence of CD4(+) Treg cells in horses, determine their suppressive function as well as their mechanism of action. Freshly isolated peripheral blood mononuclear cells (PBMC) from healthy horses were examined for CD4, CD25 and forkhead box P3 (FoxP3) expression. We show that equine FoxP3 is expressed constitutively by a population of CD4(+) CD25(+) T cells, mainly in the CD4(+) CD25(high) subpopulation. Proliferation of CD4(+) CD25(-) sorted cells stimulated with irradiated allogenic PBMC was significantly suppressed in co-culture with CD4(+) CD25(high) sorted cells in a dose-dependent manner. The mechanism of suppression by the CD4(+) CD25(high) cell population is mediated by close contact as well as interleukin (IL)-10 and transforming growth factor-beta1 (TGF-beta1) and probably other factors. In addition, we studied the in vitro induction of CD4(+) Treg and their characteristics compared to those of freshly isolated CD4(+) Treg cells. Upon stimulation with a combination of concanavalin A, TGF-beta1 and IL-2, CD4(+) CD25(+) T cells which express FoxP3 and have suppressive capability were induced from CD4(+) CD25(-) cells. The induced CD4(+) CD25(high) express higher levels of IL-10 and TGF-beta1 mRNA compared to the freshly isolated ones. Thus, in horses as in man, the circulating CD4(+) CD25(high) subpopulation contains natural Treg cells and functional Treg can be induced in vitro upon appropriate stimulation. Our study provides the first evidence of the regulatory function of CD4(+) CD25(+) cells in horses and offers insights into ex vivo manipulation of Treg cells. PMID- 21978001 TI - NOD-like receptors and RIG-I-like receptors in human eosinophils: activation by NOD1 and NOD2 agonists. AB - NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs) are newly discovered pattern-recognition receptors. They detect substructures of bacterial peptidoglycan and viral RNA, respectively, thereby initiating an immune response. However, their role in eosinophil activation remains to be explored. The aim of this study was to characterize the expression of a range of NLRs and RLRs in purified human eosinophils and assess their functional importance. Expression of NOD1, NOD2, NLRP3, RIG-I and MDA-5 was investigated using real-time reverse transcription PCR, flow cytometry and immunohistochemistry. The effects of the corresponding agonists iE-DAP (NOD1), MDP (NOD2), alum (NLRP3) and poly(I:C)/LyoVec (RIG-I/MDA-5) were studied in terms of cytokine secretion, degranulation, survival, expression of adhesion molecules and activation markers, and chemotactic migration. Eosinophils expressed NOD1 and NOD2 mRNA and protein. Low levels of RIG-I and MDA-5 were found, whereas expression of NLRP3 was completely absent. In accordance, stimulation with iE-DAP and MDP was found to induce secretion of interleukin-8, up-regulate expression of CD11b, conversely down-regulate CD62 ligand, increase expression of CD69 and induce migration. The MDP also promoted release of eosinophil-derived neurotoxin, whereas iE-DAP failed to do so. No effects were seen upon stimulation with alum or poly(I:C)/LyoVec. Moreover, the NOD1-induced and NOD2-induced activation was mediated via the nuclear factor-kappaB signalling pathway and augmented by interleukin-5 and granulocyte-macrophage colony-stimulating factor, but not interferon-gamma. Taken together, the NLR system represents a novel pathway for eosinophil activation. The responses are enhanced in the presence of cytokines that regulate T helper type 2 immunity, suggesting that the NLRs constitute a link between respiratory infections and exacerbations of allergic disease. PMID- 21978002 TI - A CD8alpha(-) subpopulation of macaque circulatory natural killer cells can mediate both antibody-dependent and antibody-independent cytotoxic activities. AB - Natural killer (NK) cells are important components of the innate immune system that mediate effector and regulatory functions. As effector cells, NK cells help control virus-infected cells through cell-mediated antibody-dependent mechanisms such as antibody-dependent cellular cytotoxicity (ADCC). Although macaques are an important and reliable animal model for the study of retrovirus-induced human diseases, and despite the crucial role played by NK cells in innate and adaptive immune responses against simian immunodeficiency virus (SIV), only a few studies have attempted to characterize different macaque NK cell subpopulations. In the present study, we identified a subpopulation of circulatory CD8alpha(-) macaque NK cells that express NK lineage markers and exhibit cytotoxic potential. CD8alpha(-) NK cells were phenotypically characterized as CD3(-) CD14(-) CD20(-) CD8alpha(-) cells that express NK cell markers including CD16, CD56, granzyme B, perforin, NKG2D and KIR2D. Based on their CD56/CD16 expression patterns, cells within the CD8alpha(-) gate can be divided into four subpopulations: CD56(dim) CD16(bright) , CD56(dim) CD16(-) , CD56(bright) CD16(-) , and CD56(-) CD16(-) cells. In contrast, CD8alpha(+) NK cells are 95% CD56(dim) CD16(bright) , which correlates with their high cytotoxic potential. Upon interleukin-15 activation, CD8alpha(-) cells up-regulated CD69 expression and produced low levels of interferon-gamma and tumour necrosis factor-alpha. Sorted CD8alpha(-) NK cells were capable of killing MHC-I-devoid target cells and mediated ADCC responses against SIV gp120-coated target cells in the presence of macaque anti-gp120 antibodies. Taking into account CD8alpha(-) myeloid dendritic cells, we show that about 35% of macaque CD8alpha(-) cells represent a novel, functional population of circulatory NK cells that possesses cytotoxic potential and is capable of mediating anti-viral immune responses. PMID- 21978003 TI - Autophagy modulates the Mycobacterium tuberculosis-induced cytokine response. AB - Both autophagy and pro-inflammatory cytokines are involved in the host defence against mycobacteria, but little is known regarding the effect of autophagy on Mycobacterium tuberculosis (MTB)-induced cytokine production. In the present study, we assessed the effect of autophagy on production of monocyte-derived and T-cell-derived cytokines, and examined whether two functional polymorphisms in autophagy genes led to altered cytokine production. Blocking autophagy inhibited tumour necrosis factor-alpha (TNF-alpha) production, while enhancing interleukin 1beta (IL-1beta) production in peripheral blood mononuclear cells stimulated with MTB. Induction of autophagy by starvation or interferon-gamma (IFN-gamma) had the opposite effect. The modulation of both TNF-alpha and IL-1beta production by autophagy was induced at the level of gene transcription. Functional polymorphisms in the autophagy genes ATG16L1 and IRGM did not have a major impact on MTB-induced cytokine production in healthy volunteers, although a moderate effect was observed on IFN-gamma production by the ATG16L1 T300A polymorphism. These data demonstrate the interplay between autophagy and inflammation during host defence against mycobacteria, and future studies to investigate the clinical implications of these effects for the susceptibility to tuberculosis are warranted. PMID- 21978005 TI - Self-assembly of copper(II) ion-mediated nanotube and its supramolecular chiral catalytic behavior. AB - Self-assembly of several low-molecular-weight L-glutamic acid-based gelators, which individually formed helical nanotube or nanofiber structures, was investigated in the presence of Cu(2+) ion. It was found that, when Cu(2+) was added into the system, the self-assembly manner changed significantly. Only in the case of bolaamphiphilic glutamic acid, N,N'-hexadecanedioyl-di-L-glutamic acid (L-HDGA), were the hydrogel formation as well as the nanotube structures maintained. The addition of Cu(2+) ion caused a transition from monolayer nanotube of L-HDGA to a multilayer nanotube with the thickness of the tubular wall about 10 nm. For the other amphiphiles, the gel was destroyed and nanofiber structures were mainly formed. The formed Cu(2+)-containing nanostructures can function as an asymmetric catalyst for Diels-Alder cycloaddition between cyclopentadiene and aza-chalcone. In comparison with the other Cu(2+)-containing nanostructures, the Cu(2+)-mediated nanotube structure showed not only accelerated reaction rate, but enhanced enantiomeric selectivity. It was suggested that, through the Cu(2+) mediated nanotube formation, the substrate molecules could be anchored on the nanotube surfaces and produced a stereochemically favored alignment. When adducts reacted with the substrate, both the enantiomeric selectivity and the reaction rate were increased. Since the Cu(2+)-mediated nanotube can be fabricated easily and in large amount, the work opened a new way to perform efficient chiral catalysis through the supramolecular gel. PMID- 21978004 TI - Compartmentalization of bone morphogenetic proteins and their antagonists in lymphoid progenitors and supporting microenvironments and functional implications. AB - Bone morphogenetic protein (BMP) signalling regulates lymphopoiesis in bone marrow and thymus via the interaction of haemato-lymphoid progenitors with the stroma microenvironment. Despite increasing functional evidence for the role of BMP signalling in lymphopoiesis, little is known of the spatial distribution of BMP/BMP antagonists in the thymus and of how BMP signals exert specific functions in developing lymphocytes. We analysed expression of BMP/BMP antagonists in the thymus and bone marrow and determined the topology of BMP/BMP antagonist expression using lacZ reporter mice. Bmp4, Bmp7, Gremlin and Twisted gastrulation (Twsg1) are all expressed in the thymus and expression was clearly different for each gene investigated. Expression was seen both in cortical and medullary regions suggesting that BMP signals regulate all stages of T-cell development. Two genes in particular, Bmp7 and Twsg1, were dynamically expressed in developing T and B lymphocytes. Their conditional ablation in all haematopoietic cells surprisingly did not affect the steady state of B-cell and T-cell development. This indicates that both lymphoid cell-derived BMP7 and TWSG1 are dispensable for normal lymphopoiesis and that bone-marrow stroma-derived TWSG1 is responsible for the lymphoid defects observed in Twsg1 null mice. In summary our data demonstrate a complex network of lymphoid and stroma derived BMP signals involved in the orchestration of lymphopoiesis in both bone marrow and thymus. PMID- 21978006 TI - Introduction to the special issue on advancing neuroscience through a systems approach. PMID- 21978008 TI - Brain anatomy, processing speed, and reading in school-age children. AB - This study was conducted to verify, prospectively, the ability of an anatomical risk index (ARI) constructed from seven anatomical measures of cerebral volume and perisylvian asymmetry to predict reading ability in 43 children aged 9 to 18. We found that negative ARIs (low cerebral volume and symmetry) were associated with poor reading ability only in children with low processing speed. Regression analysis showed that anatomy, speed, and an interaction term predicted 53% of the variance in real word reading (p < .0001). Leftward perisylvian asymmetry and larger cerebral volumes may support cognitive flexibility in children with low processing speed. PMID- 21978007 TI - Advancing neuroscience through epigenetics: molecular mechanisms of learning and memory. AB - Humans share 96% of our 30,000 genes with Chimpanzees. The 1,200 genes that differ appear at first glance insufficient to describe what makes us human and them apes. However, we are now discovering that the mechanisms that regulate how genes are expressed tell a much richer story than our DNA alone. Sections of our DNA are constantly being turned on or off, marked for easy access, or secluded and hidden away, all in response to ongoing cellular activity. In the brain, neurons encode information-in effect memories-at the cellular level. Yet while memories may last a lifetime, neurons are dynamic structures. Every protein in the synapse undergoes some form of turnover, some with half-lives of only hours. How can a memory persist beyond the lifetimes of its constitutive molecular building blocks? Epigenetics-changes in gene expression that do not alter the underlying DNA sequence-may be the answer. In this article, epigenetic mechanisms including DNA methylation and acetylation or methylation of the histone proteins that package DNA are described in the context of animal learning. Through the interaction of these modifications a "histone code" is emerging wherein individual memories leave unique memory traces at the molecular level with distinct time courses. A better understanding of these mechanisms has implications for treatment of memory disorders caused by normal aging or diseases including schizophrenia, Alzheimer's, depression, and drug addiction. PMID- 21978009 TI - Letter naming and letter writing reversals in children with dyslexia: momentary inefficiency in the phonological and orthographic loops of working memory. AB - Given mounting evidence for working memory impairments in dyslexia, letter reversals during rapid automatic letter naming (phonological loop) or rapid automatic letter writing (orthographic loop) may reflect momentary inefficiency of working memory. Few of the children, with or without dyslexia, in a multi generational family genetics study, produced reversals, but those with dyslexia produced more than those without dyslexia. Working-memory component predictors (word storing and processing units, phonological and orthographic loops, and executive functions) in regressions differentiated children with dyslexia (average age 11) who did and did not make reversals, predicted the number of reversals on specific letter naming or letter writing tasks, and explained unique variance in reading and writing outcomes. Although reversals are not a hallmark defining feature of dyslexia, children who produce reversals may benefit from instruction designed to develop specific working memory components and their efficient coordination in time. PMID- 21978011 TI - Rate- and accuracy-disabled subtype profiles among adults with dyslexia in the Hebrew orthography. AB - This study examined a subtyping scheme rooted in the dissociation between reading rate and accuracy in an exceptionally large sample of adult readers with dyslexia using a wide variety of behavioral and event-related potential (ERP) measures. Stage 1 was a behavioral study, in which basic reading skill, reading comprehension, linguistic and cognitive tasks were administered to 661 learning disabled university students (n = 382) and their non-learning-disabled peers (n = 279). Based on a word reading measure, accuracy-disabled and rate-disabled subgroups were identified, as was a subgroup with deficits in both rate and accuracy. The results support the persistence of a rate versus accuracy dissociation into adulthood. Accuracy disability was related to a broad range of deficits affecting phonological, orthographic, and morphological processing, verbal memory, attention, and reading comprehension. Rate disability appeared to be associated with slower processing of printed material, alongside largely intact functioning resembling those of skilled readers. In stage 2, electroencephalogram (EEG)-ERP measurements were obtained from 140 participants recruited from the larger sample. Activation in visual association cortex, indicated by the N170 amplitude, was found to be lower for accuracy-disabled than skilled readers, and comparable between rate-disabled and skilled readers. The lowest amplitude was found in the double-deficit subgroup. The findings support the existence of distinctive reading disability profiles, based on selective deficits in reading rate versus accuracy and associated with different basic reading, linguistic, and cognitive skills as well as electrophysiological responses. PMID- 21978010 TI - Engagement of temporal lobe regions predicts response to educational interventions in adolescent struggling readers. AB - Brain activation profiles obtained using magnetoencephalography were compared between middle-school students experiencing reading difficulties and non-reading impaired students during performance of a continuous printed word recognition task. Struggling readers underwent small-group remedial instruction, and students who showed significant gains in word reading efficiency at a one-year follow-up assessment were classified as Adequate Responders whereas those not demonstrating such gains as Inadequate Responders. At baseline, compared to Inadequate Responders, the activation profiles of Adequate Responders featured increased activity in the left middle, superior temporal, and ventral occipitotemporal regions, as well as in the right mesial temporal cortex. The degree of activity in these regions was a significant predictor of improvement in word reading efficiency beyond the prediction afforded by baseline reading accuracy or fluency measures. The engagement of brain areas that typically serve as key components of the brain circuit for reading may be an important factor in predicting response to intervention in older students who experience reading difficulties. PMID- 21978012 TI - Does development affect the error-related negativity of impaired and skilled readers? An ERP study. AB - Previous findings of reduced error-related and correct-related negativities (ERN/CRN) and semantic N400 responses associated with reading errors among impaired adult readers led to the current study on age effects on these components. Event-related potentials (ERPs) were recorded from 43 adolescents and 46 adults, including skilled readers and persons with a history of reading disability, on a lexical decision task. Adolescents exhibited smaller ERN amplitudes and larger N400 amplitudes during reading errors, presumably due to the late maturation of the prefrontal cortex. The ERN amplitude difference between impaired and skilled readers was smaller in adolescents than adults, and adolescents exhibited a smaller N400 difference between correct and erroneous responses than adults. ERN amplitude increased with age in impaired readers. It is postulated that the still developing mental lexicon among adolescents results in greater semantic effort and reduced ERN differences. PMID- 21978013 TI - Does processing a shallow and a deep orthography produce different brain activity patterns? An ERP study conducted in Hebrew. AB - Orthographies range from shallow orthographies with transparent grapheme-phoneme relations, to deep orthographies, in which these relations are opaque. Two forms of script transcribe the Hebrew language: the shallow pointed script (with diacritics) and the deep unpointed script (without diacritics). This study was set out to examine whether the reading of these scripts evokes distinct brain activity. Preliminary results indicate distinct Event-related-potentials (ERPs). As an equivalent finding was absent when ERPs of non-orthographic stimuli with and without meaningless diacritics were compared, the results imply that print specific aspects of processing account for the distinct activity elicited by the pointed and unpointed scripts. PMID- 21978014 TI - Implicit learning processes of compensated dyslexic and skilled adult readers. AB - This article presents preliminary results from two implicit learning tasks (linguistic and nonlinguistic) aimed at ascertaining whether or not compensated adult dyslexic readers have a deficit in implicit learning. The dyslexic readers and a control group were compared on measures of accuracy and reaction time. In addition, EEG measures were obtained. Initial results suggest that dyslexic readers do in fact have a deficit in implicit learning, evidenced by differences in accuracy and the P300 component, and that this deficit is more pronounced when the task at hand is linguistic. PMID- 21978015 TI - Toward an ERP-driven diagnostic approach for reading impairments. AB - This preliminary study attempted to use Event Related Brain Potentials (ERPs) to identify different causes for slow reading performance. At least two unique brain activity patterns were found for below average readers. Based on visual inspection of the N170 ERP component elicited by words in a lexical decision task, participants were either classified as N170-normal or N170-absent. Although both groups showed very dissimilar brain activity patterns, they did not differ in any reading or cognitive measures. Differences in brain activity were discussed as indicators for disturbances at specific stages of word processing, which should lead to individually adjusted intervention approaches. PMID- 21978016 TI - Can intervention programs influence how the dyslexic brain processes low-level visual stimuli? AB - This preliminary study employed event-related potentials (ERPs) to determine the effect of different intervention programs for dyslexia. Two intervention programs were used; the CogniFit Personal Coach (CPC) and the Reading Acceleration Program (RAP). Differences between a small group of dyslexic readers and a control group of regular readers were examined on two visual oddball tasks. The two oddball tasks included a non-alphabetic task and a non-contextual alphabetic one. The amplitude and latency of ERP component P1 is reported here, showing a decrease in amplitude and an increase in latency after training, suggesting an amplitude latency tradeoff after visual training. PMID- 21978018 TI - Sense and nonsense of pathway analysis software in proteomics. AB - New developments in proteomics enable scientists to examine hundreds to thousands of proteins in parallel. Quantitative proteomics allows the comparison of different proteomes of cells, tissues, or body fluids with each other. Analyzing and especially organizing these data sets is often a Herculean task. Pathway Analysis software tools aim to take over this task based on present knowledge. Companies promise that their algorithms help to understand the significance of scientist's data, but the benefit remains questionable, and a fundamental systematic evaluation of the potential of such tools has not been performed until now. Here, we tested the commercial Ingenuity Pathway Analysis tool as well as the freely available software STRING using a well-defined study design in regard to the applicability and value of their results for proteome studies. It was our goal to cover a wide range of scientific issues by simulating different established pathways including mitochondrial apoptosis, tau phosphorylation, and Insulin-, App-, and Wnt-signaling. Next to a general assessment and comparison of the pathway analysis tools, we provide recommendations for users as well as for software developers to improve the added value of a pathway study implementation in proteomic pipelines. PMID- 21978019 TI - Demonstration of quality of care measurement using the Japanese liver cancer registry. AB - AIM: Despite advances in medical therapy, studies have reported gaps between current evidence and actual practice in many areas of medicine. Process-of-care quality indicators (QIs) are tools to measure the evidence-practice gap. This study aims to examine the feasibility of applying QIs for liver cancer care to the national registry database operated by the Liver Cancer Study Group of Japan. METHODS: Prior research developed a set of process-of-care QIs developed on the basis of the Japanese Clinical Practice Guidelines for hepatocellular carcinoma. Each QI describes target patients and care processes indicated for such patients. Among the 25 developed QIs, six appeared scorable using the information contained in the dataset from the 17(th) Nationwide Survey of Primary Liver Cancer. RESULTS: In total, 16 187 patients were eligible for the six QIs for 34 599 times, among which the indicated care was provided 83.9% times. The scores ranged from 64.4% (surgical therapy in patients with HCC 3-5 cm in diameter) to 91.1% (indocyanine green checkup before surgical resection). The information was generally available to determine eligibility (78.3%-100%) and pass/fail (91.9% 99.9%) for the QIs. CONCLUSIONS: Applying QIs to the liver cancer registry, the quality of hepatocellular carcinoma care can be measured. In future, providing feedback regarding the results to the participating society may improve the quality of liver cancer care nationwide. PMID- 21978020 TI - Reduced effect of Tasmanian devil facial tumor disease at the disease front. AB - Pathogen-driven declines in animal populations are increasingly regarded as a major conservation issue. The Tasmanian devil (Sarcophilus harrisii) is threatened with extinction by devil facial tumor disease, a unique transmissible cancer. The disease is transmitted through direct transfer of tumor cells, which is possible because the genetic diversity of Tasmanian devils is low, particularly in the major histocompatibility complex genes of the immune system. The far northwest of Tasmania now holds the last remaining disease-free wild devil populations. The recent discovery of unique major histocompatibility complex genotypes in the northwestern region of Tasmania has raised the possibility that some animals may be resilient to the disease. We examined the differences in the epidemiology and population effects of devil facial tumor disease at 3 well-studied affected sites in eastern Tasmania and 1 in western Tasmania (West Pencil Pine). In contrast to the 3 eastern sites, there has been no rapid increase in disease prevalence or evidence of population decline at West Pencil Pine. Moreover, this is the only onsite at which the population age structure has remained unaltered 4 years after the first detection of disease. The most plausible explanations for the substantial differences in population effects and epidemiology of the disease between eastern and western sites are geographic differences in genotypes or phenotypes of devils and functional differences between tumor strains in the 2 regions. We suggest that conservation efforts focus on identifying whether either or both these explanations are correct and then, if resistance alleles exist, to attempt to spread the resistant alleles into affected populations. Such assisted selection has rarely been attempted for the management of wildlife diseases, but it may be widely applicable. PMID- 21978021 TI - Evaluation of spermiation indices with multiple sperm collections in endangered sterlet (Acipenser ruthenus). AB - This study investigated the effects of multiple collections of sperm on endangered sterlet (Acipenser ruthenus) sperm functional parameters [spermatozoa motility and curvilinear velocity (VCL)] as well as on protein concentration and osmolality of seminal plasma. The average sperm volume and mean spermatozoa concentration per male were significantly altered with multiple collections. On the other hand, no significant effect of multiple collections on protein concentration of seminal plasma was observed. In all experimental groups, moderate impact of sequential collection on osmolality (p < 0.05) of seminal plasma was observed. Ninety to 100% of motile spermatozoa were observed at 15 s after activation, with an average VCL of 181.12 +/- 19.10 MUm/s. After 90 s, average VCL decreased to 130 +/- 26 MUm/s. Motility was maintained for up to 4 min. The maximum percentage of motile spermatozoa was observed after the third collection of sperm. The spermatozoa VCL increased significantly with subsequent collections. The results of this study provide new data on the effects of multiple collections on quantitative and qualitative parameters of sperm in sterlet. The data confirmed that the sequential stripping has no negative effect on the percentage of motility and spermatozoa velocity. This should be beneficial for the development of sterlet aquaculture programs. PMID- 21978022 TI - Liquid water: from symmetry distortions to diffusive motion. AB - Water deviates from tetrahedral symmetry on different scales, creating "defects" that are important for its dynamics. In this Account, I trace the manifestations of these distortions from the isolated molecule through gas-phase clusters to the liquid phase. Unlike the common depiction, an isolated water molecule has a nonsymmetric charge distribution: although its positive charge is localized at the hydrogens, the negative charge is smeared between the lone-pair sites. This creates a "negativity track" along which a positive charge may slide. Consequently, the most facile motion within the water dimer is a reorientation of the hydrogen-bond (HB) accepting molecule (known as an "acceptor switch"), such that the donor hydrogen switches from one lone pair to the other. Liquid water exhibits asymmetry between donor and acceptor HBs. Molecular dynamics simulations show that the water oxygens accepting HBs from the central molecule are spatially localized, whereas water hydrogens donating HBs to it are distributed along the negativity track. This asymmetry is manifested in a wider acceptor- versus donor HB distribution. There is a higher probability for a water molecule to accept one (trigonal symmetry) or three HBs than to donate one or three HBs. A simple model can explain semiquantitatively how these distributions evolve by distorting perfectly tetrahedral water. Just two reactions are required: the dissociation of a HB between a double-donor donating to a double-acceptor, D(2)...A(2), followed by a switching reaction in which a HB donor rotates its hydrogen between two double-acceptor molecules. The preponderance of D(2)...A(2) dissociation events is in line with HB "anticooperativity", whereas positive cooperativity is exhibited by conditional HB distributions: a molecule with more acceptor bonds tends to have more donor bonds and vice versa. Quantum mechanically, such an effect arises from intermolecular charge transfer, but it is observed even for fixed-charge water models. Possibly, in the liquid state this is partly a collective effect, for example, a more ordered hydration shell that enhances the probability for both acceptor and donor HBs. The activation energy for liquid water self-diffusion is considerably larger than its HB strength, pointing to the involvement of collective dynamics. The remarkable agreement between the temperature dependence of the water self-diffusion coefficient and its Debye relaxation time suggests that both share the same mechanism, likely consisting of coupled rotation and translation with collective rearrangement of the environment. The auto-correlation function of a hydrogen-bonded water molecule pair is depicted quantitatively by the solution of the diffusion equation for reversible geminate recombination, up to long times where the ubiquitous t(-3/2) power law prevails. From the model, one obtains the HB dissociation and formation rate coefficients and their temperature dependence. Both have a similar activation enthalpy, suggesting rapid formation of HBs with alternate partners, perhaps by the HB switching reaction involving the trigonal site. A detailed picture of how small fluctuations evolve into large-scale molecular motions in water remains elusive. Nonetheless, our results demonstrate how the plasticity of water can be traced to its asymmetric charge distribution, with duality between tetrahedral and trigonal ligation states. PMID- 21978023 TI - Graphene oxide based photoinduced charge transfer label-free near-infrared fluorescent biosensor for dopamine. AB - While the super fluorescence quenching capacity of graphene and graphene oxide (GO) has been extensively employed to develop fluorescent sensors, their own unique fluorescence and its potential for chemo-/biosensing have seldom been explored. Here we report a GO-based photoinduced charge transfer (PCT) label-free near-infrared (near-IR) fluorescent biosensor for dopamine (DA). The multiple noncovalent interactions between GO and DA and the ultrafast decay at the picosecond range of the near-IR fluorescence of GO resulted in effective self assembly of DA molecules on the surface of GO, and significant fluorescence quenching, allowing development of a PCT-based biosensor with direct readout of the near-IR fluorescence of GO for selective and sensitive detection of DA. The developed method gave a detection limit of 94 nM and a relative standard deviation of 2.0% for 11 replicate detections of 2.0 MUM DA and was successfully applied to the determination of DA in biological fluids with quantitative recovery (98-115%). PMID- 21978024 TI - Stathmin: a protein with many tasks. New biomarker and potential target in cancer. AB - INTRODUCTION: Stathmin is a microtubule-destabilizing phosphoprotein, firstly identified as the downstream target of many signal transduction pathways. Several studies then indicated that stathmin is overexpressed in many types of human malignancies, thus deserving the name of Oncoprotein 18 (Op18). At molecular level, stathmin depolymerizes microtubules by either sequestering free tubulin dimers or directly inducing microtubule-catastrophe. A crucial role for stathmin in the control of mitosis has been proposed, since both its overexpression and its downregulation induce failure in the correct completion of cell division. Accordingly, stathmin is an important target of the main regulator of M phase, cyclin-dependent kinase 1. AREAS COVERED: Recent evidences support a role for stathmin in the regulation of cell growth and motility, both in vitro and in vivo, and indicate its involvement in advanced, invasive and metastatic cancer more than in primary tumors. EXPERT OPINION: Many studies suggest that high stathmin expression levels in cancer negatively influence the response to microtubule-targeting drugs. These notions together with the fact that stathmin is expressed at very low levels in most adult tissues strongly support the use of stathmin as marker of prognosis and as target for novel anti-tumoral and anti metastatic therapies. PMID- 21978025 TI - Evaluation of the hypertensive patients in southeastern Anatolia; demographic features and target organ damage. AB - We investigated the socio-demographic characteristics, blood and pulse pressure, and end organ damage of hypertensive patients applying to an outpatient cardiology clinic in southeastern Anatolia. End organ damage in 100 consecutive hypertensive patients was defined by left ventricular hypertrophy, retinopathy, and albuminuria. The determined independent risk factors of left ventricular hypertrophy were advanced age and low educational level; of nephropathy were high pulse pressure and unawareness of the name of anti-hypertensive drug; and for retinopathy were high pulse pressure and female gender. In order to prevent end organ damage, the most important aspect to focus on is patient training and pulse pressure. PMID- 21978026 TI - Blood pressure lowering effect of the extract of aerial parts of Capparis aphylla is mediated through endothelium-dependent and independent mechanisms. AB - This investigation was aimed to provide pharmacological evidences for the medicinal use of Capparis aphylla in hypertension. In normotensive anesthetized rats, intravenous administration of the crude extract of Capparis aphylla (Ca.Cr; 3-100 mg/kg) caused a fall in mean arterial pressure (MAP), which was partially blocked in the presence of atropine (2 mg/kg). In isolated rabbit aortic rings, Ca.Cr inhibited phenylephrine (1 MUM) and high K(+) (80 mM) precontractions with respective EC(50) values of 0.10 (0.07-0.15) and 1.22 mg/mL (1.00-1.50), suggesting calcium channel blocking (CCB) activity with a predominant inhibitory effect on receptor operated Ca(2+) channels. Pretreatment of the arotic rings with Ca.Cr (0.1-1 mg/mL) caused a rightward shift in the Ca(2+) concentration response curves, similar to verapamil. In isolated rat aorta preparations, Ca.Cr caused a partial endothelium-dependent L-NAME/atropine-sensitive vasodilator effect. In guinea-pig atria, Ca.Cr suppressed both rate and force of spontaneous atrial contractions with respective EC(50) values of 1.35 (1.01-1.79) and 1.60 mg/mL (1.18-2.17), which remained unchanged in the presence of atropine (1 MUM). These data indicate that the blood pressure (BP) lowering effect of the crude extract of Capparis aphylla is mediated through a vasodilator and cardiac depressant effect. The vasodilator effect is partly mediated by an endothelium dependent, atropine-sensitive NO pathway, while the CCB effect is partly responsible for endothelium-independent vasodilatation and also for the cardiac depressant effect; thus, this study provides pharmacologic evidence with respect to the medicinal use of the plant in hypertension. PMID- 21978027 TI - Assessment of sympathovagal imbalance by spectral analysis of heart rate variability in prehypertensive and hypertensive patients in Indian population. AB - Though the incidence of hypertension has increased considerably in recent years, the pathophysiologic mechanism that causes progression from stage of prehypertension to hypertension has not been fully elucidated. Therefore, the present study was conducted to assess the sympathovagal imbalance in prehypertensives and hypertensives by spectral analysis of heart rate variability (HRV) to understand the nature of change in autonomic balance in this common dysfunction of mankind. Body mass index (BMI), basal heart rate (BHR), blood pressure (BP), and spectral indices of HRV such as total power (TP), normalized low frequency power (LFnu), normalized high frequency power (HFnu), ratio of low frequency power to high frequency power (LF-HF ratio), mean heart rate (mean RR), square root of the mean squared differences of successive normal to normal intervals (RMSSD), the number of interval differences of successive NN intervals greater than 50 ms (NN50), and the proportion derived by dividing NN50 by the total number of NN intervals (pNN50) were assessed in three groups of subjects: normotensives (n = 32), prehypertensives (n = 28), and hypertensives (n = 31). Sympathovagal balance was analyzed and correlated with BMI, BHR, and BP in all the groups. It was observed that autonomic imbalance in prehypertensives was due to proportionate increased sympathetic activity and vagal inhibition, whereas in hypertensives, vagal withdrawal was more prominent than sympathetic overactivity. The LF-HF ratio, the sensitive indicator of sympathovagal balance, was significantly correlated with BMI, BHR, and BP. It was concluded that vagal inhibition plays an important role in the critical alteration of sympathovagal balance in the development of clinical hypertension in prehypertensive subjects. PMID- 21978028 TI - Role of genetic variants in the gene encoding lipocalin-2 in the development of elevated blood pressure. AB - Lipocalin-2 is recently recognized as a biomarker of obesity and inflammation, which are both risk factors for hypertension. We therefore investigated the association of common single nucleotide polymorphisms (SNPs) in the gene encoding lipocalin-2 (LCN2) with elevated blood pressure (BP) in Hong Kong Chinese. Five tagging SNPs were genotyped in 1936 subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2) with a median follow-up time of 6.4 years. Elevated BP was defined as >=130/85 mmHg or taking anti-hypertensive medication. Haplotype GGTCC was associated with elevated BP at follow-up after adjusting for age and sex (odds ratio (OR) [95% confidence interval (CI)] = 1.17 [1.01-1.36], P = 0.031). Haplotype GGTCC was also an associated plasma CRP level 11.7% (95% CI: 2.6-25.9%) higher among subjects with elevated BP after adjusting for age and sex (P = 0.036). Among 1381 subjects without elevated BP at baseline, 321 subjects developed elevated BP at follow-up. Haplotype GGTCC was associated with the development of elevated BP at follow-up after adjusting for baseline age, sex, systolic blood pressure (SBP), and follow-up duration (OR [95% CI] = 1.30 [1.06-1.58], P = 0.011). Among subjects not taking anti-hypertensive medication, carriers of the haplotype GGTCC had higher SBP than noncarriers (119.7 +/- 16.4 mmHg vs. 117.9 +/- 17.3 mmHg, P = 0.043). Our findings suggest, for the first time, that genetic variants in LCN2 may affect BP. Further studies on the role of lipocalin-2 in BP regulation are warranted. PMID- 21978029 TI - End-to-end azide-bridged manganese(III) chain compounds: field-induced magnetic phase transitions and variation of T(C) to 38 K depending on the side groups of the Schiff bases. AB - Three one-dimensional coordination polymers [Mn(L)(N(3))](n) [L = L1 (1), L2 (2), L3 (3); L1H(2) = N,N'-bis(5-chlorosalicylideneiminato)-1,3-diaminopentane, L2H(2) = N,N'-bis(5-bromosalicylideneiminato)-1,3-diaminopentane, L3H(2) = N,N'-bis(5 bromosalicylideneiminato)-1,3-diamino-2-dimethylpropane] bridged by end-to-end azides were prepared. The crystal systems differ according to the Schiff bases used. Each Mn atom adopts a typical Jahn-Teller distortion. The helicity of the chains occurs in a racemic manner only for 2. No noncovalent forces are relevant in 2, while pi-pi contacts are visible in 1 and 3. Magnetic measurements show the presence of apparent spin canting. Complexes 1 and 3 exhibit a field-induced metamagnetic transition from an antiferromagnetic state to a weak ferromagnetic phase, whereas 2 embraces a field-induced two-step magnetic phase transition. The critical temperature is observed at 38 K for 2, which is relatively higher than those for 1 (11 K) and 3 (10 K). The pronounced long-range order may contribute from intrachain exchange couplings and through-space dipolar interactions between adjacent chains. PMID- 21978030 TI - Detergents stabilize the conformation of phosphodiesterase 6. AB - Membrane-bound phosphodiesterase 6 (PDE6) plays an important role in visual signal transduction by regulating cGMP levels in rod photoreceptor cells. Our understanding of PDE6 catalysis and structure suffers from inadequate characterization of the alpha and beta subunit catalytic core, interactions of the core with two intrinsically disordered, proteolysis-prone inhibitory PDEgamma (Pgamma) subunits, and binding of two types of isoprenyl-binding protein delta, called PrBP/delta, to the isoprenylated C-termini of the catalytic core. Structural studies of native PDE6 have been also been hampered by the lack of a heterologous expression system for the holoenzyme. In this work, we purified PDE6 in the presence of PrBP/delta and screened for additives and detergents that selectively suppress PDE6 basal activity while sparing that of the trypsin activated enzyme. Some detergents removed PrBP/delta from the PDE complex, separating it from the holoenzyme after PDE6 purification. Additionally, selected detergents also significantly reduced the level of dissociation of PDE6 subunits, increasing their homogeneity and stabilizing the holoenzyme by substituting for its native membrane environment. PMID- 21978031 TI - Validity of the utrecht scale for evaluation of rehabilitation-participation. AB - PURPOSE: There is still a need for a generic participation instrument that measures both objective and subjective participation in adults living in the community and that is feasible for use in rehabilitation practice. The Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-Participation) was developed to satisfy this need, comprising 31 items in three scales: Frequency, Restrictions and Satisfaction. The aim of this study was to examine the validity of this measure. METHODS: Cross-sectional study involving former rehabilitation outpatients from five rehabilitation facilities in the Netherlands (n = 395). The Frenchay Activities Index (FAI), the participation subtotal score of the ICF Measure of Participation and Activities Screener (IMPACT-SP) and the Participation Scale were included as reference measures. RESULTS: Internal consistency of the USER-Participation scales was satisfactory (alpha 0.70-0.91). Spearman correlations between these scales were between 0.36 and 0.52. Concurrent validity was shown by strong correlations between the Frequency scale and the FAI (0.59), the Restrictions scale and the IMPACT-SP (0.75) and the Satisfaction scale and the Participation Scale (-0.73). Discriminant validity was shown by significant differences in USER-Participation scores between participants with different levels of independence and between participants with different health conditions. CONCLUSION: The USER-Participation appears to be a valid measure to rate objective and subjective participation in persons with physical disabilities. PMID- 21978035 TI - Point/counterpoint: pulsed reduced dose rate radiation therapy is likely to become the treatment modality of choice for recurrent cancers. PMID- 21978036 TI - Bridging the gap between IMRT and VMAT: dense angularly sampled and sparse intensity modulated radiation therapy. AB - PURPOSE: To propose an alternative radiation therapy (RT) planning and delivery scheme with optimal angular beam sampling and intrabeam modulation for improved dose distribution while maintaining high delivery efficiency. METHODS: In the proposed approach, coined as dense angularly sampled and sparse intensity modulated RT (DASSIM-RT), a large number of beam angles are used to increase the angular sampling, leading to potentially more conformal dose distributions as compared to conventional IMRT. At the same time, intensity modulation of the incident beams is simplified to eliminate the dispensable segments, compensating the increase in delivery time caused by the increased number of beams and facilitating the plan delivery. In a sense, the proposed approach shifts and transforms, in an optimal fashion, some of the beam segments in conventional IMRT to the added beams. For newly available digital accelerators, the DASSIM-RT delivery can be made very efficient by concatenating the beams so that they can be delivered sequentially without operator's intervention. Different from VMAT, the level of intensity modulation in DASSIS-RT is field specific and optimized to meet the need of each beam direction. Three clinical cases (a head and neck (HN) case, a pancreas case, and a lung case) are used to evaluate the proposed RT scheme. DASSIM-RT, VMAT, and conventional IMRT plans are compared quantitatively in terms of the conformality index (CI) and delivery efficiency. RESULTS: Plan quality improves generally with the number and intensity modulation of the incident beams. For a fixed number of beams or fixed level of intensity modulation, the improvement saturates after the intensity modulation or number of beams reaches to a certain level. An interplay between the two variables is observed and the saturation point depends on the values of both variables. For all the cases studied here, the CI of DASSIM-RT with 15 beams and 5 intensity levels (0.90, 0.79, and 0.84 for the HN, pancreas, and lung cases, respectively) is similar with that of conventional IMRT with seven beams and ten intensity levels (0.88, 0.79, and 0.83) and is higher than that of single-arc VMAT (0.75, 0.75, and 0.82). It is also found that the DASSIM-RT plans generally have better sparing of organs-at-risk than IMRT plans. It is estimated that the dose delivery time of DASSIM-RT with 15 beams and 5 intensity levels is about 4.5, 4.4, and 4.2 min for the HN, pancreas, and lung case, respectively, similar to that of IMRT plans with 7 beams and 10 intensity levels. CONCLUSION: DASSIS-RT bridges the gap between IMRT and VMAT and allows optimal sampling of angular space and intrabeam modulation, thus it provides improved conformity in dose distributions while maintaining high delivery efficiency. PMID- 21978037 TI - Evaluation of a 3D local multiresolution algorithm for the correction of partial volume effects in positron emission tomography. AB - PURPOSE: Partial volume effects (PVEs) are consequences of the limited spatial resolution in emission tomography leading to underestimation of uptake in tissues of size similar to the point spread function (PSF) of the scanner as well as activity spillover between adjacent structures. Among PVE correction methodologies, a voxel-wise mutual multiresolution analysis (MMA) was recently introduced. MMA is based on the extraction and transformation of high resolution details from an anatomical image (MR/CT) and their subsequent incorporation into a low-resolution PET image using wavelet decompositions. Although this method allows creating PVE corrected images, it is based on a 2D global correlation model, which may introduce artifacts in regions where no significant correlation exists between anatomical and functional details. METHODS: A new model was designed to overcome these two issues (2D only and global correlation) using a 3D wavelet decomposition process combined with a local analysis. The algorithm was evaluated on synthetic, simulated and patient images, and its performance was compared to the original approach as well as the geometric transfer matrix (GTM) method. RESULTS: Quantitative performance was similar to the 2D global model and GTM in correlated cases. In cases where mismatches between anatomical and functional information were present, the new model outperformed the 2D global approach, avoiding artifacts and significantly improving quality of the corrected images and their quantitative accuracy. CONCLUSIONS: A new 3D local model was proposed for a voxel-wise PVE correction based on the original mutual multiresolution analysis approach. Its evaluation demonstrated an improved and more robust qualitative and quantitative accuracy compared to the original MMA methodology, particularly in the absence of full correlation between anatomical and functional information. PMID- 21978038 TI - Reliable automatic alignment of tomographic projection data by passive auto focus. AB - PURPOSE: The authors present a robust algorithm that removes the blurring and double-edge artifacts in high-resolution computed tomography (CT) images that are caused by misaligned scanner components. This alleviates the time-consuming process of physically aligning hardware, which is of particular benefit if components are moved or swapped frequently. METHODS: The proposed method uses the experimental data itself for calibration. A parameterized model of the scanner geometry is constructed and the parameters are varied until the sharpest 3D reconstruction is found. The concept is similar to passive auto-focus algorithms of digital optical instruments. The parameters are used to remap the projection data from the physical detector to a virtual aligned detector. This is followed by a standard reconstruction algorithm, namely the Feldkamp algorithm. Feldkamp et al. [J. Opt. Soc. Am. A 1, 612-619 (1984)]. RESULTS: An example implementation is given for a rabbit liver specimen that was collected with a circular trajectory. The optimal parameters were determined in less computation time than that for a full reconstruction. The example serves to demonstrate that (a) sharpness is an appropriate measure for projection alignment, (b) our parameterization is sufficient to characterize misalignments for cone-beam CT, and (c) the procedure determines parameter values with sufficient precision to remove the associated artifacts. CONCLUSIONS: The algorithm is fully tested and implemented for regular use at The Australian National University micro-CT facility for both circular and helical trajectories. It can in principle be applied to more general imaging geometries and modalities. It is as robust as manual alignment but more precise since we have quantified the effect of misalignment. PMID- 21978039 TI - Noise reduction in spectral CT: reducing dose and breaking the trade-off between image noise and energy bin selection. AB - PURPOSE: Our purpose was to reduce image noise in spectral CT by exploiting data redundancies in the energy domain to allow flexible selection of the number, width, and location of the energy bins. METHODS: Using a variety of spectral CT imaging methods, conventional filtered backprojection (FBP) reconstructions were performed and resulting images were compared to those processed using a Local HighlY constrained backPRojection Reconstruction (HYPR-LR) algorithm. The mean and standard deviation of CT numbers were measured within regions of interest (ROIs), and results were compared between FBP and HYPR-LR. For these comparisons, the following spectral CT imaging methods were used:(i) numerical simulations based on a photon-counting, detector-based CT system, (ii) a photon-counting, detector-based micro CT system using rubidium and potassium chloride solutions, (iii) a commercial CT system equipped with integrating detectors utilizing tube potentials of 80, 100, 120, and 140 kV, and (iv) a clinical dual-energy CT examination. The effects of tube energy and energy bin width were evaluated appropriate to each CT system. RESULTS: The mean CT number in each ROI was unchanged between FBP and HYPR-LR images for each of the spectral CT imaging scenarios, irrespective of bin width or tube potential. However, image noise, as represented by the standard deviation of CT numbers in each ROI, was reduced by 36%-76%. In all scenarios, image noise after HYPR-LR algorithm was similar to that of composite images, which used all available photons. No difference in spatial resolution was observed between HYPR-LR processing and FBP. Dual energy patient data processed using HYPR-LR demonstrated reduced noise in the individual, low- and high-energy images, as well as in the material-specific basis images. CONCLUSIONS: Noise reduction can be accomplished for spectral CT by exploiting data redundancies in the energy domain. HYPR-LR is a robust method for reducing image noise in a variety of spectral CT imaging systems without losing spatial resolution or CT number accuracy. This method improves the flexibility to select energy bins in the manner that optimizes material identification and separation without paying the penalty of increased image noise or its corollary, increased patient dose. PMID- 21978040 TI - Improved motion-compensated image reconstruction for PET using sensitivity correction per respiratory gate and an approximate tube-of-response backprojector. AB - PURPOSE: One limitation of positron emission tomography (PET) imaging of the torso is patient motion. Motion-compensated image reconstruction (MCIR) is one method employed to reduce the deleterious effects of motion. Existing MCIR algorithms use a single sensitivity correction term, which provides inexact normalization for multigate data. Consequently, in this study, the authors derive and examine the performance of an MCIR algorithm with sensitivity correction per gate. In addition, they demonstrate an approximate tube-of-response (TOR) backprojector. METHODS: Simulated data from the NCAT phantom with six lesions added were used to compare MCIR algorithms with and without the incorporation of sensitivity correction per gate and TOR backprojection to postreconstruction registration (PRR) and images reconstructed without motion correction. To make the simulations more realistic, intragate motion was included. Deformation fields were determined from NCAT anatomical images using a free-form deformation approach with bending energy regularization. RESULTS: Sensitivity correction per gate and TOR backprojection improved mean lesion contrast-to-noise ratio by 6% 8%, with the maximum increase (21%-23%) found for the smallest lesion. These increases were obtained despite a small increase (3%) in noise as measured by standard deviation in a uniform lung region. Sensitivity correction per gate comes at no extra computational cost, whilst replacing line-of-response backprojection with TOR backprojection increased the overall computation time by ~20%. In addition, MCIR was found to be superior to PRR, with one factor contributing to this difference being the differential impact of interpolation following deformation. MCIR was also shown to exhibit super-resolution. CONCLUSIONS: Replacing a single sensitivity correction term in MCIR with sensitivity correction per gate improves lesion detectability. For a small increase in computational expense, further improvements are achieved using an approximate TOR backprojector rather than line-of-response backprojection. PMID- 21978041 TI - The effect of electronically steering a phased array ultrasound transducer on near-field tissue heating. AB - PURPOSE: This study presents the results obtained from both simulation and experimental techniques that show the effect of mechanically or electronically steering a phased array transducer on proximal tissue heating. METHODS: The thermal response of a nine-position raster and a 16-mm diameter circle scanning trajectory executed through both electronic and mechanical scanning was evaluated in computer simulations and experimentally in a homogeneous tissue-mimicking phantom. Simulations were performed using power deposition maps obtained from the hybrid angular spectrum (HAS) method and applying a finite-difference approximation of the Pennes' bioheat transfer equation for the experimentally used transducer and also for a fully sampled transducer to demonstrate the effect of acoustic window, ultrasound beam overlap and grating lobe clutter on near field heating. RESULTS: Both simulation and experimental results show that electronically steering the ultrasound beam for the two trajectories using the 256-element phased array significantly increases the thermal dose deposited in the near-field tissues when compared with the same treatment executed through mechanical steering only. In addition, the individual contributions of both beam overlap and grating lobe clutter to the near-field thermal effects were determined through comparing the simulated ultrasound beam patterns and resulting temperature fields from mechanically and electronically steered trajectories using the 256-randomized element phased array transducer to an electronically steered trajectory using a fully sampled transducer with 40 401 phase-adjusted sample points. CONCLUSIONS: Three distinctly different three distinctly different transducers were simulated to analyze the tradeoffs of selected transducer design parameters on near-field heating. Careful consideration of design tradeoffs and accurate patient treatment planning combined with thorough monitoring of the near field tissue temperature will help to ensure patient safety during an MRgHIFU treatment. PMID- 21978042 TI - 4D analysis of influence of patient movement and anatomy alteration on the quality of 3D U/S-based prostate HDR brachytherapy treatment delivery. AB - PURPOSE: Modern HDR brachytherapy treatment for prostate cancer based on the 3D ultrasound (U/S) plays increasingly important role. The purpose of this study is to investigate possible patient movement and anatomy alteration between the clinical image set acquisition, made after the needle implantation, and the patient irradiation and their influence on the quality of treatment. METHODS: The authors used 3D U/S image sets and the corresponding treatment plans based on a 4D-treatment planning procedure: plans of 25 patients are obtained right after the needle implantation (clinical plan is based on this 3D image set) and just before and after the treatment delivery. The authors notice the slight decrease of treatment quality with increase of time gap between the clinical image set acquisition and the patient irradiation. 4D analysis of dose-volume-histograms (DVHs) for prostate: CTV1 = PTV, and urethra, rectum, and bladder as organs at risk (OARs) and conformity index (COIN) is presented, demonstrating the effect of prostate, OARs, and needles displacement. RESULTS: The authors show that in the case that the patient body movement/anatomy alteration takes place, this results in modification of DVHs and radiobiological parameters, hence the plan quality. The observed average displacement of needles (1 mm) and of prostate (0.57 mm) is quite small as compared with the average displacement noted in several other reports [A. A. Martinez et al., Int. J. Radiat. Oncol., Biol., Phys. 49(1), 61-69 (2001); S. J. Damore et al., Int. J. Radiat. Oncol., Biol., Phys. 46(5), 1205 1211 (2000); P. J. Hoskin et al., Radiotherm. Oncol. 68(3), 285-288 (2003); E. Mullokandov et al., Int. J. Radiat. Oncol., Biol., Phys. 58(4), 1063-1071 (2004)] in the literature. CONCLUSIONS: Although the decrease of quality of dosimetric and radiobiological parameters occurs, this does not cause clinically unacceptable changes to the 3D dose distribution, according to our clinical protocol. PMID- 21978043 TI - Characterization of the deflections of a catheter steered using a magnetic resonance imaging system. AB - PURPOSE: The authors quantify the deflections of a catheter and a guidewire in MR setting with different designs of ferromagnetic tips and a system of high gradient coils which can generate gradients, and thus forces, 20 times larger than a conventional scanner. METHODS: Different designs of catheter tips are experimentally tested in an effort to maximize the deflections. One to two ferromagnetic spheres are attached at the distal tip of the catheter (or guidewire) with different spacing between the spheres. The effect of dipole dipole interaction on the steering of the catheter is studied through experimentation and theoretical modeling. The effect of using many spheres on the artefact generated in fast imaging sequences is also investigated. RESULTS: A catheter and a guidewire are successfully steered by applying magnetic gradients inside a magnetic resonance scanner. More ferromagnetic material allows for larger magnetic forces, however, the use of two ferromagnetic spheres introduces undesired dipole-dipole interactions. Two ferromagnetic spheres generate a single larger artefact as they are close together. CONCLUSIONS: By varying the distance between the two ferromagnetic spheres, a balance can be struck between the need to minimize the size of the tip and the undesirable dipole-dipole interaction. PMID- 21978044 TI - Long range node-strut analysis of trabecular bone microarchitecture. AB - PURPOSE: We present a new morphometric measure of trabecular bone microarchitecture, called mean node strength (NdStr), which is part of a newly developed approach called long range node-strut analysis. Our general aim is to describe and quantify the apparent "latticelike" microarchitecture of the trabecular bone network. METHODS: Similar in some ways to the topological node strut analysis introduced by Garrahan et al. [J. Microsc. 142, 341-349 (1986)], our method is distinguished by an emphasis on long-range trabecular connectivity. Thus, while the topological classification of a pixel (after skeletonization) as a node, strut, or terminus, can be determined from the 3 * 3 neighborhood of that pixel, our method, which does not involve skeletonization, takes into account a much larger neighborhood. In addition, rather than giving a discrete classification of each pixel as a node, strut, or terminus, our method produces a continuous variable, node strength. The node strength is averaged over a region of interest to produce the mean node strength of the region. RESULTS: We have applied our long range node-strut analysis to a set of 26 high-resolution peripheral quantitative computed tomography (pQCT) axial images of human proximal tibiae acquired 17 mm below the tibial plateau. We found that NdStr has a strong positive correlation with trabecular volumetric bone mineral density (BMD). After an exponential transformation, we obtain a Pearson's correlation coefficient of r = 0.97. Qualitative comparison of images with similar BMD but with very different NdStr values suggests that the latter measure has successfully quantified the prevalence of the "latticelike" microarchitecture apparent in the image. Moreover, we found a strong correlation (r = 0.62) between NdStr and the conventional node-terminus ratio (Nd/Tm) of Garrahan et al. The Nd/Tm ratios were computed using traditional histomorphometry performed on bone biopsies obtained at the same location as the pQCT scans. CONCLUSIONS: The newly introduced morphometric measure allows a quantitative assessment of the long-range connectivity of trabecular bone. One advantage of this method is that it is based on pQCT images that can be obtained noninvasively from patients, i.e., without having to obtain a bone biopsy from the patient. PMID- 21978045 TI - Dosimetry protocol for the preclinical trials in white-beam minibeam radiation therapy. AB - PURPOSE: In the quest of a curative radiotherapy treatment for gliomas, new delivery modes are being explored. At the Biomedical Beamline of the European Synchrotron Radiation Facility, a new spatially fractionated technique, called minibeam radiation therapy (MBRT), is under development. The aims of this work were to assess different dosimetric aspects and to establish a dosimetry protocol to be applied in the forthcoming animal (rat) studies in order to evaluate the therapeutic index of this new radiotherapy approach. METHODS: Absolute dosimetry was performed with a thimble ionization chamber (PTW semiflex 31010) whose center was positioned at 2 g cm(-2) depth. To translate the dose measured in broad beam configuration to the dose deposited with a minibeam, the scatter factors were used. Those were assessed by using the Monte Carlo simulations and verified experimentally with Gafchromic films and a Bragg Peak chamber. The comparison of the theoretical and experimental data were used to benchmark the calculations. Finally, the dose distributions in a rat phantom were evaluated by using the validated Monte Carlo calculations. RESULTS: The absolute dosimetry in broad beam configuration was measured in reference conditions. The dose rate was in the range between 168 and 224 Gy/min, depending on the storage ring current. A scatter factor of 0.80 +/- 0.04 was obtained. Percentage depth dose and lateral profiles were evaluated both in homogenous and heterogeneous slab phantoms. The general good agreement between Monte Carlo simulations and experimental data permitted the benchmark of the calculations. Finally, the peak doses in the rat head phantom were assessed from the measurements in reference conditions. In addition, the peak-to-valley dose ratio values as a function of depth in the rat head were evaluated. CONCLUSIONS: A new promising radiotherapy approach is being explored at the ESRF: Minibeam Radiation Therapy. To assess the therapeutic index of this new modality, in vivo experiments are being planned, for which an accurate knowledge of the dosimetry is essential. For that purpose, a complete set of measurements and Monte Carlo simulations was performed. The first dosimetry protocol for preclinical trials in minibeam radiation therapy was established. This protocol allows to have reproducibility in terms of dose for the different biological studies. PMID- 21978046 TI - Optimizing the accuracy of a helical diode array dosimeter: a comprehensive calibration methodology coupled with a novel virtual inclinometer. AB - PURPOSE: The goal of any dosimeter is to be as accurate as possible when measuring absolute dose to compare with calculated dose. This limits the uncertainties associated with the dosimeter itself and allows the task of dose QA to focus on detecting errors in the treatment planning (TPS) and/or delivery systems. This work introduces enhancements to the measurement accuracy of a 3D dosimeter comprised of a helical plane of diodes in a volumetric phantom. METHODS: We describe the methods and derivations of new corrections that account for repetition rate dependence, intrinsic relative sensitivity per diode, field size dependence based on the dynamic field size determination, and positional correction. Required and described is an accurate "virtual inclinometer" algorithm. The system allows for calibrating the array directly against an ion chamber signal collected with high angular resolution. These enhancements are quantitatively validated using several strategies including ion chamber measurements taken using a "blank" plastic shell mimicking the actual phantom, and comparison to high resolution dose calculations for a variety of fields: static, simple arcs, and VMAT. A number of sophisticated treatment planning algorithms were benchmarked against ion chamber measurements for their ability to handle a large air cavity in the phantom. RESULTS: Each calibration correction is quantified and presented vs its independent variable(s). The virtual inclinometer is validated by direct comparison to the gantry angle vs time data from machine log files. The effects of the calibration are quantified and improvements are seen in the dose agreement with the ion chamber reference measurements and with the TPS calculations. These improved agreements are a result of removing prior limitations and assumptions in the calibration methodology. Average gamma analysis passing rates for VMAT plans based on the AAPM TG-119 report are 98.4 and 93.3% for the 3%/3 mm and 2%/2 mm dose-error/distance to agreement threshold criteria, respectively, with the global dose-error normalization. With the local dose-error normalization, the average passing rates are reduced to 94.6 and 85.7% for the 3%/3 mm and 2%/2 mm criteria, respectively. Some algorithms in the convolution/superposition family are not sufficiently accurate in predicting the exit dose in the presence of a 15 cm diameter air cavity. CONCLUSIONS: Introduction of the improved calibration methodology, enabled by a robust virtual inclinometer algorithm, improves the accuracy of the dosimeter's absolute dose measurements. With our treatment planning and delivery chain, gamma analysis passing rates for the VMAT plans based on the AAPM TG-119 report are expected to be above 91% and average at about 95% level for gamma(3%/3 mm) with the local dose-error normalization. This stringent comparison methodology is more indicative of the true VMAT system commissioning accuracy compared to the often quoted dose-error normalization to a single high value. PMID- 21978047 TI - A modeling approach to predict acoustic nonlinear field generated by a transmitter with an aluminum lens. AB - PURPOSE: In this work, the authors propose a modeling approach to compute the nonlinear acoustic field generated by a flat piston transmitter with an attached aluminum lens. METHODS: In this approach, the geometrical parameters (radius and focal length) of a virtual source are initially determined by Snell's refraction law and then adjusted based on the Rayleigh integral result in the linear case. Then, this virtual source is used with the nonlinear spheroidal beam equation (SBE) model to predict the nonlinear acoustic field in the focal region. RESULTS: To examine the validity of this approach, the calculated nonlinear result is compared with those from the Westervelt and (Khokhlov-Zabolotskaya-Kuznetsov) KZK equations for a focal intensity of 7 kW/cm(2). Results indicate that this approach could accurately describe the nonlinear acoustic field in the focal region with less computation time. CONCLUSIONS: The proposed modeling approach is shown to accurately describe the nonlinear acoustic field in the focal region. Compared with the Westervelt equation, the computation time of this approach is significantly reduced. It might also be applicable for the widely used concave focused transmitter with a large aperture angle. PMID- 21978048 TI - Clinical accuracy of ExacTrac intracranial frameless stereotactic system. AB - PURPOSE: In this paper, the authors assess the accuracy of the Brainlab ExacTrac system for frameless intracranial stereotactic treatments in clinical practice. METHODS: They recorded couch angle and image fusion results (comprising lateral, longitudinal, and vertical shifts, and rotation corrections about these axes) for 109 stereotactic radiosurgery and 166 stereotactic radiotherapy patient treatments. Frameless stereotactic treatments involve iterative 6D image fusion corrections applied until the results conform to customizable pass criteria, theirs being 0.7 mm and 0.5 degrees for each axis. The planning CT slice thickness was 1.25 mm. It has been reported in the literature that the CT slices' thickness impacts the accuracy of localization to bony anatomy. The principle of invariance with respect to patient orientation was used to determine spatial accuracy. RESULTS: The data for radiosurgery comprised 927 image pairs, of which 532 passed (pass ratio of 57.4%). The data for radiotherapy comprised 15983 image pairs, of which 10 050 passed (pass ratio of 62.9%). For stereotactic radiotherapy, the combined uncertainty of ExacTrac calibration, image fusion, and intrafraction motion was (95% confidence interval) 0.290-0.302 and 0.306-0.319 mm in the longitudinal and lateral axes, respectively. The combined uncertainty of image fusion and intrafraction motion in the anterior-posterior coordinates was 0.174-0.182 mm. For stereotactic radiosurgery, the equivalent ranges are 0.323 0.393, 0.337-0.409, and 0.231-0.281 mm. The overall spatial accuracy was 1.24 mm for stereotactic radiotherapy (SRT) and 1.35 mm for stereotactic radiosurgery (SRS). CONCLUSIONS: The ExacTrac intracranial frameless stereotactic system spatial accuracy is adequate for clinical practice, and with the same pass criteria, SRT is more accurate than SRS. They now use frameless stereotaxy exclusively at their center. PMID- 21978049 TI - Measuring signal-to-noise ratio in partially parallel imaging MRI. AB - PURPOSE: To assess five different methods of signal-to-noise ratio (SNR) measurement for partially parallel imaging (PPI) acquisitions. METHODS: Measurements were performed on a spherical phantom and three volunteers using a multichannel head coil a clinical 3T MRI system to produce echo planar, fast spin echo, gradient echo, and balanced steady state free precession image acquisitions. Two different PPI acquisitions, generalized autocalibrating partially parallel acquisition algorithm and modified sensitivity encoding with acceleration factors (R) of 2-4, were evaluated and compared to nonaccelerated acquisitions. Five standard SNR measurement techniques were investigated and Bland-Altman analysis was used to determine agreement between the various SNR methods. The estimated g-factor values, associated with each method of SNR calculation and PPI reconstruction method, were also subjected to assessments that considered the effects on SNR due to reconstruction method, phase encoding direction, and R-value. RESULTS: Only two SNR measurement methods produced g factors in agreement with theoretical expectations (g >= 1). Bland-Altman tests demonstrated that these two methods also gave the most similar results relative to the other three measurements. R-value was the only factor of the three we considered that showed significant influence on SNR changes. CONCLUSIONS: Non signal methods used in SNR evaluation do not produce results consistent with expectations in the investigated PPI protocols. Two of the methods studied provided the most accurate and useful results. Of these two methods, it is recommended, when evaluating PPI protocols, the image subtraction method be used for SNR calculations due to its relative accuracy and ease of implementation. PMID- 21978050 TI - The influence of field strength and different clinical breast MRI protocols on the outcome of texture analysis using foam phantoms. AB - PURPOSE: Texture analysis (TA) has proved to be useful to distinguish different tissues and disease states using magnetic resonance imaging (MRI). TA has been successfully applied clinically to improve identification of abnormalities in the brain, liver, and bone and, more recently, has been used to enhance the specificity of breast MRI. This preclinical study used a custom-made phantom containing different grades of reticulated foam embedded in agarose gel to assess the capability of TA to distinguish between different texture objects, under different imaging conditions. The aim was to assess whether TA could be used reliably with clinical protocols that were not optimized for texture analysis and also to investigate the effect that changing imaging sequence parameters would have on the outcome of TA. METHODS: Clinical fast gradient echo sequences and two different breast RF coils were used in order to reflect standard clinical practice. Three protocols were used: (1) a high spatial resolution protocol run on a 1.5 Tesla (T) MRI scanner, (2) a parameter matched sequence run on a 3.0 T magnet, and (3) a high temporal resolution protocol also run on a 3.0 T magnet.For each protocol, three sequence parameters (repetition time, bandwidth/echo time, and flip angle) were altered from the baseline values to assess the impact of changes in acquisition parameters on the outcome of TA. RESULTS: TA was performed using MAZDA software and clearly differentiated four foam phantoms when using the wavelet transform method (WAV), also moderately so with the co-occurrence matrix method (COM). The outcome was generally improved for imaging protocols acquired on the 3.0 T scanner, particularly for the high spatial resolution protocol where changes to the acquisition parameters influenced the TA, especially changes to the bandwidth/echo time. For the other protocols, TA outcome was less affected by changes to the imaging parameters. CONCLUSIONS: This phantom study shows that acquisition parameters and protocols that are typically used for clinical breast imaging can result in good TA. Our findings suggest that changes to sequence parameters may not greatly influence the outcome of texture analysis, but rather that spatial resolution may be the most important factor to consider. PMID- 21978051 TI - Safety considerations for IMRT: executive summary. AB - This report on intensity-modulated radiation therapy (IMRT) is part of a series of white papers addressing patient safety commissioned by the American Society for Radiation Oncology's (ASTRO) Target Safely Campaign. The document has been approved by the ASTRO Board of Directors, endorsed by the American Association of Physicists in Medicine (AAPM) and American Association of Medical Dosimetrists (AAMD), and reviewed and accepted by the American College of Radiology's Commission on Radiation Oncology. This report is related to other reports of the ASTRO white paper series on patient safety which are still in preparation, and when appropriate it defers to guidance that will be published by those groups in future white papers. This document takes advantage of the large body of work on quality assurance and quality control principles within radiation oncology whenever possible. IMRT provides increased capability to conform isodose distributions to the shape of the target(s), thereby reducing dose to some adjacent critical structures. This promise of IMRT is one of the reasons for its widespread use. However, the promise of IMRT is counterbalanced by the complexity of the IMRT planning and delivery processes, and the associated risks, some of which have been demonstrated by the New York Times reports on serious accidents involving both IMRT and other radiation treatment modalities. This report provides an opportunity to broadly address safe delivery of IMRT, with a primary focus on recommendations for human error prevention and methods to reduce the occurrence of errors or machine malfunctions that can lead to catastrophic failures or errors. PMID- 21978052 TI - Robustness of phase retrieval methods in X-ray phase contrast imaging: a comparison. AB - PURPOSE: The robustness of the phase retrieval methods is of critical importance for limiting and reducing radiation doses involved in x-ray phase contrast imaging. This work is to compare the robustness of two phase retrieval methods by analyzing the phase maps retrieved from the experimental images of a phantom. METHODS: Two phase retrieval methods were compared. One method is based on the transport of intensity equation (TIE) for phase contrast projections, and the TIE based method is the most commonly used method for phase retrieval in the literature. The other is the recently developed attenuation-partition based (AP based) phase retrieval method. The authors applied these two methods to experimental projection images of an air-bubble wrap phantom for retrieving the phase map of the bubble wrap. The retrieved phase maps obtained by using the two methods are compared. RESULTS: In the wrap's phase map retrieved by using the TIE based method, no bubble is recognizable, hence, this method failed completely for phase retrieval from these bubble wrap images. Even with the help of the Tikhonov regularization, the bubbles are still hardly visible and buried in the cluttered background in the retrieved phase map. The retrieved phase values with this method are grossly erroneous. In contrast, in the wrap's phase map retrieved by using the AP-based method, the bubbles are clearly recovered. The retrieved phase values with the AP-based method are reasonably close to the estimate based on the thickness-based measurement. The authors traced these stark performance differences of the two methods to their different techniques employed to deal with the singularity problem involved in the phase retrievals. CONCLUSIONS: This comparison shows that the conventional TIE-based phase retrieval method, regardless if Tikhonov regularization is used or not, is unstable against the noise in the wrap's projection images, while the AP-based phase retrieval method is shown in these experiments to be superior to the TIE-based method for the robustness in performing the phase retrieval. PMID- 21978053 TI - In vivo MR acoustic radiation force imaging in the porcine liver. AB - PURPOSE: High intensity focused ultrasound (HIFU) in the abdomen can be sensitive to acoustic aberrations that can exist in the beam path of a single sonication. Having an accurate method to quickly visualize the transducer focus without damaging tissue could assist with executing the treatment plan accurately and predicting these changes and obstacles. By identifying these obstacles, MR acoustic radiation force imaging (MR-ARFI) provides a reliable method for visualizing the transducer focus quickly without damaging tissue and allows accurate execution of the treatment plan. METHODS: MR-ARFI was used to view the HIFU focus, using a gated spin echo flyback readout-segmented echo-planar imaging sequence. HIFU spots in a phantom and in the livers of five live pigs under general anesthesia were created with a 550 kHz extracorporeal phased array transducer initially localized with a phase-dithered MR-tracking sequence to locate microcoils embedded in the transducer. MR-ARFI spots were visualized, observing the change of focal displacement and ease of steering. Finally, MR-ARFI was implemented as the principle liver HIFU calibration system, and MR-ARFI measurements of the focal location relative to the thermal ablation location in breath-hold and breathing experiments were performed. RESULTS: Measuring focal displacement with MR-ARFI was achieved in the phantom and in vivo liver. In one in vivo experiment, where MR-ARFI images were acquired repeatedly at the same location with different powers, the displacement had a linear relationship with power [y = 0.04x + 0.83 MUm (R(2) = 0.96)]. In another experiment, the displacement images depicted the electronic steering of the focus inside the liver. With the new calibration system, the target focal location before thermal ablation was successfully verified. The entire calibration protocol delivered 20.2 J of energy to the animal (compared to greater than 800 J for a test thermal ablation). ARFI displacement maps were compared with thermal ablations during seven breath-hold ablations. The error was 0.83 +/- 0.38 mm in the S/I direction and 0.99 +/- 0.45 mm in the L/R direction. For six spots in breathing ablations, the mean error in the nonrespiration direction was 1.02 +/- 0.89 mm. CONCLUSIONS: MR-ARFI has the potential to improve free-breathing plan execution accuracy compared to current calibration and acoustic beam adjustment practices. Gating the acquisition allows for visualization of the focal spot over the course of respiratory motion, while also being insensitive to motion effects that can complicate a thermal test spot. That MR-ARFI measures a mechanical property at the focus also makes it insensitive to high perfusion, of particular importance to highly perfused organs such as the liver. PMID- 21978054 TI - Factors for conversion between human and automatic read-outs of CDMAM images. AB - PURPOSE: According to the European protocol for the quality control of the physical and technical aspects of mammography screening (EPQCM) image quality of digital mammography devices has to be assessed using human evaluation of the CDMAM contrast-detail phantom. This is accomplished by the determination of threshold thicknesses of gold disks with different diameters (0.08-2 mm) and revealed to be very time consuming. Therefore a software solution based on a nonprewhitening matched filter (NPW) model was developed at the University of Nijmegen. Factors for the conversion from automatic to human readouts have been determined by Young et al. [Proc. SPIE 614206, 1-13 (2006) and Proc. SPIE 6913, 69131C1 (2008)] using a huge amount of data of both human and automatic readouts. These factors depend on the observer groups and are purely phenomenological. The authors present an alternative approach to determine the factors by using the Rose observer model. METHODS: Their method uses the Rose theory which gives a relationship between threshold contrast, diameter of the object and number of incident photons. To estimate the conversion factors for the five diameters from 0.2 to 0.5 mm they exposed with five different current-time products which resulted in 25 equations with five unknowns. RESULTS: The theoretical conversion factors (in dependence of the diameters) amounted to be 1.61 +/- 0.02 (0.2 mm diameter), 1.67 +/- 0.02 (0.25 mm), 1.85 +/- 0.02 (0.31 mm), 2.09 +/- 0.02 (0.4 mm), and 2.28 +/- 0.02 (0.5 mm). The corresponding phenomenological factors found in literature are 1.74 (0.2 mm), 1.78 (0.25 mm), 1.83 (0.31 mm), 1.88 (0.4 mm), and 1.93 (0.5 mm). CONCLUSIONS: They transferred the problem of determining the factors to a well known observer model which has been examined for many years and is also well established. This method reveals to be reproduceable and produces factors comparable to the phenomenological ones. PMID- 21978055 TI - A method for patient dose reduction in dynamic contrast enhanced CT study. AB - PURPOSE: In dynamic contrast enhanced CT (DCE-CT) study, prolonged CT scanning with high temporal resolution is required to give accurate and precise estimates of kinetic parameters. However, such scanning protocol could lead to substantial radiation dose to the patient. A novel method is proposed to reduce radiation dose to patient, while maintaining high accuracy for kinetic parameter estimates in DCE-CT study. METHODS: The method is based on a previous investigation that the arterial impulse response (AIR) in DCE-CT study can be predicted using a population-based scheme. In the proposed method, DCE-CT scanning is performed with relatively low temporal resolution, hence, giving rise to reduction in patient dose. A novel method is proposed to estimate the arterial input function (AIF) based on the coarsely sampled AIF. By using the estimated AIF in the tracer kinetic analysis of the coarsely sampled DCE-CT study, the calculated kinetic parameters are able to achieve a high degree of accuracy. The method was tested on a DCE-CT data set of 48 patients with cervical cancer scanned at high temporal resolution. A random cohort of 34 patients was chosen to construct the orthonormal bases of the AIRs via singular value decomposition method. The determined set of orthonormal bases was used to fit the AIFs in the second cohort (14 patients) at varying levels of down sampling. For each dataset in the second cohort, the estimated AIF was used for kinetic analyses of the modified Tofts and adiabatic tissue homogeneity models for each of the down-sampling schemes between intervals from 2 to 15 s. The results were compared with analyses done with the "raw" down-sampled AIF. RESULTS: In the first group of 34 patients, there were 11 orthonormal bases identified to describe the AIRs. The AIFs in the second group were estimated in high accuracy based on the 11 orthonormal bases established in the first group along with down-sampled AIFs. Using the 11 orthonormal bases, the estimated AIFs for the second group were found to have an averaged maximal percentage error of 3.4% +/- 7.5% in all sampling schemes up to 15 s. The results of kinetic analysis with the proposed method compared with down sampling alone showed that the proposed method is superior in maintaining the accuracy in volume transfer constant (K(trans) ) after 9 s down-sampling interval, blood volume (v(b) ) for almost all down-sampling intervals, and blood flow (F) after 11 s down-sampling interval. The preliminary results suggested that the proposed method is able to support scanning intervals of 10-15 s at a cost of 6.2%-10.0% loss in accuracy of K(trans) and 10.9%-19.4% in v(b), and the scanning intervals of 12-15 s at a cost of 9.7%-14.6% for F in DEC-CT studies for patients with cervix cancer. CONCLUSIONS: The proposed method of AIF estimation allows low scanning frequency in DCE-CT study to reduce radiation dose to patient, while maintaining relatively high accuracy in the kinetic parameter estimates. The initial results suggested that the method is applicable for DCE-CT studies for patients with cervical cancer. PMID- 21978056 TI - A planning and delivery study of a rotational IMRT technique with burst delivery. AB - PURPOSE: A novel rotational IMRT (rIMRT) technique using burst delivery (continuous gantry rotation with beam off during MLC repositioning) is investigated. The authors evaluate the plan quality and delivery efficiency and accuracy of this dynamic technique with a conventional flat 6 MV photon beam. METHODS: Burst-delivery rIMRT was implemented in a planning system and delivered with a 160-MLC linac. Ten rIMRT plans were generated for five anonymized patient cases encompassing head and neck, brain, prostate, and prone breast. All plans were analyzed retrospectively and not used for treatment. Among the varied plan parameters were the number of optimization points, number of arcs, gantry speed, and gantry angle range (alpha) over which the beam is turned on at each optimization point. Combined rotational/step-and-shoot rIMRT plans were also created by superimposing multiple-segment static fields at several optimization points. The rIMRT trial plans were compared with each other and with plans generated using helical tomotherapy and VMAT. Burst-mode rotational IMRT plans were delivered and verified using a diode array, ionization chambers, thermoluminescent dosimeters, and film. RESULTS: Burst-mode rIMRT can achieve plan quality comparable to helical tomotherapy, while the former may lead to slightly better OAR sparing for certain cases and the latter generally achieves slightly lower hot spots. Few instances were found in which increasing the number of optimization points above 36, or superimposing step-and-shoot IMRT segments, led to statistically significant improvements in OAR sparing. Using an additional rIMRT partial arc yielded substantial OAR dose improvements for the brain case. Measured doses from the rIMRT plan delivery were within 4% of the plan calculation in low dose gradient regions. Delivery time range was 228-375 s for single-arc rIMRT 200-cGy prescription with a 300 MU/min dose rate, comparable to tomotherapy and VMAT. CONCLUSIONS: Rotational IMRT with burst delivery, whether combined with static fields or not, yields clinically acceptable and deliverable treatment plans. PMID- 21978057 TI - Reference dosimetry during diagnostic CT examination using XR-QA radiochromic film model. AB - PURPOSE: The authors applied 2D reference dosimetry protocol for dose measurements using XR-QA radiochromic film model during diagnostic computed tomography (CT) examinations carried out on patients and humanoid Rando phantom. METHODS: Response of XR-QA model GAFCHROMICTM film reference dosimetry system was calibrated in terms of Air-Kerma in air. Four most commonly used CT protocols were selected on their CT scanner (GE Lightspeed VCT 64), covering three anatomical sites (head, chest, and abdomen). For each protocol, 25 patients ongoing planned diagnostic CT examination were recruited. Surface dose was measured using four or eight film strips taped on patients' skin and on Rando phantom. Film pieces were scanned prior to and after irradiation using Epson ExpressionTM 10000XL document scanner. Optical reflectance of the unexposed film piece was subtracted from exposed one to obtain final net reflectance change, which is subsequently converted to dose using previously established calibration curves. RESULTS: The authors' measurements show that body skin dose variation has a sinusoidal pattern along the scanning axis due to the helical movement of the x ray tube, and a comb pattern for head dose measurements due to its axial movement. Results show that the mean skin dose at anterior position for patients is (51 +/- 6) mGy, (29 +/- 11) mGy, (45 +/- 13) mGy and (38 +/- 20) mGy for head, abdomen, angio Abdomen, and chest and abdomen protocol (UP position), respectively. The obtained experimental dose length products (DLP) show higher values than CT based DLP taken from the scanner console for body protocols, but lower values for the head protocol. Internal dose measurements inside the phantom's head indicate nonuniformity of dose distribution within scanned volume. CONCLUSIONS: In this work, the authors applied an Air-Kerma in air based radiochromic film reference dosimetry protocol for in vivo skin dose measurements. In this work, they employed green channel extracted from the scanned RGB image for dose measurements in the range from 0 to 200 mGy. Measured skin doses and corresponding DLPs were higher than DLPs provided by the CT scanner manufacturer as they were measured on patients' skin. PMID- 21978058 TI - Improved image quality for X-ray CT imaging of gel dosimeters. AB - PURPOSE: This study provides a simple method for improving precision of X-ray computed tomography (CT) scans of irradiated polymer gel dosimetry. The noise affecting CT scans of irradiated gels has been an impediment to the use of clinical CT scanners for gel dosimetry studies. METHODS: In this study, it is shown that multiple scans of a single PAGAT gel dosimeter can be used to extrapolate a "zero-scan" image which displays a similar level of precision to an image obtained by averaging multiple CT images, without the compromised dose measurement resulting from the exposure of the gel to radiation from the CT scanner. RESULTS: When extrapolating the zero-scan image, it is shown that exponential and simple linear fits to the relationship between Hounsfield unit and scan number, for each pixel in the image, provide an accurate indication of gel density. CONCLUSIONS: It is expected that this work will be utilized in the analysis of three-dimensional gel volumes irradiated using complex radiotherapy treatments. PMID- 21978059 TI - Characterization of an x-ray phase contrast imaging system based on the miniature synchrotron MIRRORCLE-6X. AB - PURPOSE: The implementation of in-line x-ray phase contrast imaging (PCI) for soft-tissue patient imaging is hampered by the lack of a bright and spatially coherent x-ray source that fits into the hospital environment. This article provides a quantitative characterization of the phase-contrast enhancement of a PCI system based on the miniature synchrotron technology MIRRORCLE-6X. METHODS: The phase-contrast effect was measured using an edge response of a plexiglass plate as a function of the incident angle of radiation. We have developed a comprehensive x-ray propagation model based on the system's components, properties, and geometry in order to interpret the measurement data. Monte-Carlo simulations are used to estimate the system's spectral properties and resolution. RESULTS: The measured ratio of the detected phase-contrast to the absorption contrast is currently in the range 100% to 200%. Experiments show that with the current implementation of the MIRRORCLE-6X, a target smaller than 30-40 MUm does not lead to a larger phase-contrast. The reason for this is that the fraction of x-rays produced by the material (carbon filament and glue) that is used for mounting the target in the electron beam is more than 25% of the total amount of x-rays produced. This increases the apparent source size. The measured phase contrast is at maximum two times larger than the absorption contrast with the current set-up. CONCLUSIONS: Calculations based on our model of the present imaging system predict that the phase-contrast can be up to an order of magnitude larger than the absorption contrast in case the materials used for mounting the target in the electron beam do not (or hardly) produce x-rays. The methods described in this paper provide vital feedback for guiding future modifications to the design of the x-ray target of MIRRORCLE-type system and configuration of the in-line PCI systems in general. PMID- 21978060 TI - Implementing RapidArc into clinical routine: a comprehensive program from machine QA to TPS validation and patient QA. AB - PURPOSE: With the increased commercial availability of intensity modulated arc therapy (IMAT) comes the need for comprehensive QA programs, covering the different aspects of this newly available technology. This manuscript proposes such a program for the RapidArc (RA) (Varian Medical Systems, Palo Alto) IMAT solution. METHODS: The program was developed and tested out for a Millennium120 MLC on iX Clinacs and a HighDefinition MLC on a Novalis TX, using a variety of measurement equipment including Gafchromic film, 2D ion chamber arrays (Seven29 and StarCheck, PTW, Freiburg, Germany) with inclinometer and Octavius phantom, the Delta4 systam (ScandiDos, Uppsala, Sweden) and the portal imager (EPID). First, a number of complementary machine QA tests were developed to monitor the correct interplay between the accelerating/decelerating gantry, the variable dose rate and the MLC position, straining the delivery to the maximum allowed limits. Second, a systematic approach to the validation of the dose calculation for RA was adopted, starting with static gantry and RA specific static MLC shapes and gradually moving to dynamic gantry, dynamic MLC shapes. RA plans were then optimized on a series of artificial structures created within the homogeneous Octavius phantom and within a heterogeneous lung phantom. These served the double purpose of testing the behavior of the optimization algorithm (PRO) as well as the precision of the forward dose calculation. Finally, patient QA on a series of clinical cases was performed with different methods. In addition to the well established in-phantom QA, we evaluated the portal dosimetry solution within the Varian approach. RESULTS: For routine machine QA, the "Snooker Cue" test on the EPID proved to be the most sensitive to overall problem detection. It is also the most practical one. The "Twinkle" and "Sunrise" tests were useful to obtain well differentiated information on the individual treatment delivery components. The AAA8.9 dose calculations showed excellent agreement with all corresponding measurements, except in areas where the 2.5 mm fixed fluence resolution was insufficient to accurately model the tongue and groove effect or the dose through nearly closed opposing leafs. Such cases benefited from the increased fluence resolution in AAA10.0. In the clinical RA fields, these effects were smeared out spatially and the impact of the fluence resolution was considerably less pronounced. The RA plans on the artificial structure sets demonstrated some interesting characteristics of the PRO8.9 optimizer, such as a sometimes unexpected dependence on the collimator rotation and a suboptimal coverage of targets within lung tissue. Although the portal dosimetry was successfully validated, we are reluctant to use it as a sole means of patient QA as long as no gantry angle information is embedded. CONCLUSIONS: The all-in validation program allows a systematic approach in monitoring the different levels of RA treatments. With the systematic approach comes a better understanding of both the capabilities and the limits of the used solution. The program can be useful for implementation, but also for the validation of major upgrades. PMID- 21978061 TI - Dosimetric intercomparison for multicenter clinical trials using a patient-based anatomic pelvic phantom. AB - PURPOSE: To assess dose delivery accuracy to clinically significant points in a realistic patient geometry for two separate pelvic radiotherapy scenarios. METHODS: An inhomogeneous pelvic phantom was transported to 36 radiotherapy centers in Australia and New Zealand. The phantom was treated according to Phase III rectal and prostate trial protocols. Point dose measurements were made with thermoluminescent dosimeters (TLDs) and an ionisation chamber. Comprehensive site demographic, treatment planning, and physical data were collected for correlation with measurement outcomes. RESULTS: Dose delivery to the prescription point for the rectal treatment was consistent with planned dose (mean difference between planned and measured dose - 0.1 +/- 0.3% std err). Dose delivery in the region of the sacral hollow was consistently higher than planned (+1.2 +/- 0.2%). For the prostate treatment, dose delivery to the prostate volume was consistent with planned doses (-0.49 +/- 0.2%) and planned dose uniformity, though with a tendency to underdose the PTV at the prostate-rectal border. Measured out-of field doses were significantly higher than planned. CONCLUSIONS: A phantom based on realistic anatomy and heterogeneity can be used to comprehensively assess the influence of multiple aspects of the radiotherapy treatment process on dose delivery. The ability to verify dose delivery for two trials with a single phantom was advantageous. PMID- 21978063 TI - A general framework and review of scatter correction methods in cone beam CT. Part 2: scatter estimation approaches. AB - The main components of scatter correction procedures are scatter estimation and a scatter compensation algorithm. This paper completes a previous paper where a general framework for scatter compensation was presented under the prerequisite that a scatter estimation method is already available. In the current paper, the authors give a systematic review of the variety of scatter estimation approaches. Scatter estimation methods are based on measurements, mathematical-physical models, or combinations of both. For completeness they present an overview of measurement-based methods, but the main topic is the theoretically more demanding models, as analytical, Monte-Carlo, and hybrid models. Further classifications are 3D image-based and 2D projection-based approaches. The authors present a system-theoretic framework, which allows to proceed top-down from a general 3D formulation, by successive approximations, to efficient 2D approaches. A widely useful method is the beam-scatter-kernel superposition approach. Together with the review of standard methods, the authors discuss their limitations and how to take into account the issues of object dependency, spatial variance, deformation of scatter kernels, external and internal absorbers. Open questions for further investigations are indicated. Finally, the authors refer on some special issues and applications, such as bow-tie filter, offset detector, truncated data, and dual-source CT. PMID- 21978062 TI - Investigating the limit of detectability of a positron emission mammography device: a phantom study. AB - PURPOSE: A new positron emission mammography (PEM) device (PEM Flex Solo II, Naviscan Inc., San Diego, CA) has recently been introduced and its performance characteristics have been documented. However, no systematic assessment of its limit of detectability has been evaluated. The aim of this work is to investigate the limit of detectability of this new PEM system using a novel, customized breast phantom. METHODS: Two sets of F-18 infused gelatin breast phantoms of varying thicknesses (2, 4, 6, and 8 cm) were constructed with and without (blank) small, shell-less contrast objects (2 mm thick disks) of varying diameters (3 14.5 mm) [volumes: 0.15-3.3 cc] and activity concentration to background ratio (ACR) (2.7-58). For the phantom set with contrast objects, the disks were placed centrally inside the phantoms and both phantom sets were imaged for a period of 10 min on the PEM device. In addition, scans for the 2 and 6 cm phantoms were repeated at different times (0, 90, and 150 min) post phantom construction to evaluate the impact of total activity concentration (count density) on lesion detectability. Each object from each phantom scan was then segmented and placed randomly in a corresponding blank phantom image. The resulting individual images were presented blindly to seven physician observers (two nuclear medicine and five breast imaging radiologists) and scored in a binary fashion (1-correctly identified object, 0-incorrect). The sensitivity, specificity, and accuracy of lesion detectability were calculated and plots of sensitivity versus ACR and lesion diameters for different phantom thicknesses and count density were generated. RESULTS: The overall (mean) detection sensitivity across all variables was 0.68 (95% CI: [0.64, 0.72]) with a corresponding specificity of 0.93 [0.87, 0.98], and diagnostic accuracy of 0.72 [0.70, 0.75]. The smallest detectable object varied strongly as a function of ACR, as sensitivity ranged from 0.36 [0.29, 0.44] for the smallest lesion size (3 mm) to 0.80 [0.75, 0.84] for the largest (14.5 mm). CONCLUSIONS: The detectability performance of this PEM system demonstrated its ability to resolve small objects with low activity concentration ratios which may assist in the identification of early stage breast cancer. The results of this investigation can be used to correlate lesion detectability with tumor size, ACR, count rate, and breast thickness. PMID- 21978064 TI - Experimental generation of an arbitrarily rotated field-free line for the use in magnetic particle imaging. AB - PURPOSE: The concept of a magnetic field-free line (FFL), with regard to the novel tomographic modality magnetic particle imaging (MPI), was recently introduced. Theoretical approaches predict the improvement of sensitivity of MPI by a factor of ten replacing the conventionally used field-free point (FFP) by a FFL. In this work, an experimental apparatus for generating an arbitrarily rotated and translated FFL field is described and tested. METHODS: A theoretical motivation for the implemented setup is provided and the required currents are derived in dependency of the coil sensitivities. A prototype of a FFL field generator is manufactured and the fields are measured using a Hall effect sensor. An evaluation of the generated fields is performed via comparison to simulated data. RESULTS: To utilize the FFL concept for MPI, the setup generating the fields needs to be feasible in praxis with respect to power loss. Furthermore, rotating and translating the FFL, while keeping the setup static in space, is a crucial aspect for conveying FFL imaging to clinical applications. The implemented setup copes with both of these challenges and allows for experimental generation as well as evaluation of the required fields. The generated fields agree to within 3.5% of model predictions. CONCLUSIONS: This work transfers the FFL concept from theoretical considerations to the implementation of an experimental setup generating the required fields. The high agreement of the measured fields with simulated data indicates the feasibility of magnetic field generation for the implementation of FFL imaging in MPI. PMID- 21978065 TI - Preliminary investigations for the option to use fast uniform scanning with compensators on a gantry designed for IMPT. AB - PURPOSE: In this experimental study, the authors explored the possibility to deliver the dose for proton therapy with fast uniform scanning on a gantry primarily designed for the delivery of conformal beam scanning and IMPT. The uniform scanning submode has been realized without equipment modifications by using the same small pencil beam used for conformal scanning, resulting in reduced realization costs. Uniform scanning has recently been adopted in a few proton therapy centers, as a basic beam delivery solution, and as an alternative to the use of scattering foils. The option to use such a mode to mimic scattering on a full-fledged scanning gantry could be of interest for treating some specific indications and as a possible solution for treating moving targets. METHODS: Uniform iso-energy dose layers were painted by fast magnetic scanning alternated with fast energy changes with the gantry beam line. The layers were stacked and repainted appropriately to produce homogeneous three-dimensional dose distributions. A collimator/compensator was used to adjust the dose to coincide laterally/distally with the target volume. In addition, they applied volumetric repainting, since they are confident that this will further mitigate the effects of organ motion as compared with the presently used clinical scanning solutions. With the approach presented in this paper, they can profit from the higher flexibility of the scanning system to obtain additional advantages. For instance the shape of the energy layers can be adjusted to the projected target shape in order to reduce treatment time and neutrons produced in the collimator. The shape of the proximal layers can be shrunk, according to the cross section of the target at the corresponding range. This provides variable range modulation (proximal conformity) while standard scattering only provides fixed range modulation with unnecessary 100% dose proximal to the target. The field-specific hardware for a spherical target volume was mounted on the Gantry 2 nozzle. One field with proximal field size shrinking and one without, each of 1 Gy, were delivered. The dose distributions at different depths were recorded as CCD images of a scintillating screen. RESULTS: The time to scan the volume once was about 4 s and the total delivery time was approximately 30 s. For the field with proximal conformity, dose sparing of up to 25% was measured in the region proximal to the target. A repainting capability of 48 times was achieved on the most distal layer. The proximal layers were repainted more due to the contribution of the plateau dose from the deeper layers. CONCLUSIONS: The flexibility of a fast scanning gantry with very fast energy changes can easily provide beam delivery by uniform layer stacking with a significant degree of volumetric repainting and with the benefit of a dose reduction proximal to the target volume. PMID- 21978066 TI - PARETO: A novel evolutionary optimization approach to multiobjective IMRT planning. AB - PURPOSE: In radiation therapy treatment planning, the clinical objectives of uniform high dose to the planning target volume (PTV) and low dose to the organs at-risk (OARs) are invariably in conflict, often requiring compromises to be made between them when selecting the best treatment plan for a particular patient. In this work, the authors introduce Pareto-Aware Radiotherapy Evolutionary Treatment Optimization (pareto), a multiobjective optimization tool to solve for beam angles and fluence patterns in intensity-modulated radiation therapy (IMRT) treatment planning. METHODS: pareto is built around a powerful multiobjective genetic algorithm (GA), which allows us to treat the problem of IMRT treatment plan optimization as a combined monolithic problem, where all beam fluence and angle parameters are treated equally during the optimization. We have employed a simple parameterized beam fluence representation with a realistic dose calculation approach, incorporating patient scatter effects, to demonstrate feasibility of the proposed approach on two phantoms. The first phantom is a simple cylindrical phantom containing a target surrounded by three OARs, while the second phantom is more complex and represents a paraspinal patient. RESULTS: pareto results in a large database of Pareto nondominated solutions that represent the necessary trade-offs between objectives. The solution quality was examined for several PTV and OAR fitness functions. The combination of a conformity-based PTV fitness function and a dose-volume histogram (DVH) or equivalent uniform dose (EUD) -based fitness function for the OAR produced relatively uniform and conformal PTV doses, with well-spaced beams. A penalty function added to the fitness functions eliminates hotspots. Comparison of resulting DVHs to those from treatment plans developed with a single-objective fluence optimizer (from a commercial treatment planning system) showed good correlation. Results also indicated that pareto shows promise in optimizing the number of beams. CONCLUSIONS: This initial evaluation of the evolutionary optimization software tool pareto for IMRT treatment planning demonstrates feasibility and provides motivation for continued development. Advantages of this approach over current commercial methods for treatment planning are many, including: (1) fully automated optimization that avoids human controlled iterative optimization and potentially improves overall process efficiency, (2) formulation of the problem as a true multiobjective one, which provides an optimized set of Pareto nondominated solutions refined over hundreds of generations and compiled from thousands of parameter sets explored during the run, and (3) rapid exploration of the final nondominated set accomplished by a graphical interface used to select the best treatment option for the patient. PMID- 21978067 TI - Monte Carlo-based simulation of dynamic jaws tomotherapy. AB - PURPOSE: Original TomoTherapy systems may involve a trade-off between conformity and treatment speed, the user being limited to three slice widths (1.0, 2.5, and 5.0 cm). This could be overcome by allowing the jaws to define arbitrary fields, including very small slice widths (<1 cm), which are challenging for a beam model. The aim of this work was to incorporate the dynamic jaws feature into a Monte Carlo (MC) model called TomoPen, based on the MC code PENELOPE, previously validated for the original TomoTherapy system. METHODS: To keep the general structure of TomoPen and its efficiency, the simulation strategy introduces several techniques: (1) weight modifiers to account for any jaw settings using only the 5 cm phase-space file; (2) a simplified MC based model called FastStatic to compute the modifiers faster than pure MC; (3) actual simulation of dynamic jaws. Weight modifiers computed with both FastStatic and pure MC were compared. Dynamic jaws simulations were compared with the convolution/superposition (C/S) of TomoTherapy in the "cheese" phantom for a plan with two targets longitudinally separated by a gap of 3 cm. Optimization was performed in two modes: asymmetric jaws-constant couch speed ("running start stop," RSS) and symmetric jaws-variable couch speed ("symmetric running start stop," SRSS). Measurements with EDR2 films were also performed for RSS for the formal validation of TomoPen with dynamic jaws. RESULTS: Weight modifiers computed with FastStatic were equivalent to pure MC within statistical uncertainties (0.5% for three standard deviations). Excellent agreement was achieved between TomoPen and C/S for both asymmetric jaw opening/constant couch speed and symmetric jaw opening/variable couch speed, with deviations well within 2%/2 mm. For RSS procedure, agreement between C/S and measurements was within 2%/2 mm for 95% of the points and 3%/3 mm for 98% of the points, where dose is greater than 30% of the prescription dose (gamma analysis). Dose profiles acquired in transverse and longitudinal directions through the center of the phantom were also compared with excellent agreement (2%/2 mm) between all modalities. CONCLUSIONS: The combination of weights modifiers and interpolation allowed implementing efficiently dynamic jaws and dynamic couch features into TomoPen at a minimal cost in terms of efficiency (simulation around 8 h on a single CPU). PMID- 21978068 TI - Resolving axon fiber crossings at clinical b-values: an evaluation study. AB - PURPOSE: Diffusion tensor magnetic resonance imaging is widely used to study the structure of the fiber pathways of brain white matter. However, the diffusion tensor cannot capture complex intravoxel fiber architecture such as fiber crossings of bifurcations. Consequently, a number of methods have been proposed to recover intravoxel fiber bundle orientations from high angular resolution diffusion imaging scans, optimized to resolve fiber crossings. It is important to improve the brain tractography by applying these multifiber methods to diffusion tensor protocols with a clinical b- value (low), which are optimized on computing tensor scalar statistics. In order to characterize the variance among different methods, consequently to be able to select the most appropriate one for a particular application, it is desirable to compare them under identical experimental conditions. METHODS: In this work, the authors study how QBall, spherical deconvolution, persistent angular structure, stick and ball, diffusion basis functions, and analytical QBall methods perform under clinically-realistic scanning conditions, where the b-value is typically lower (around 1000 s/mm(2)), and the number of diffusion encoding orientations is fewer (30-60) than in dedicated high angular resolution diffusion imaging scans. To characterize the performance of the methods, they consider the accuracy of the estimated number of fibers, the relative contribution of each fiber population to the total magnetic resonance signal, and the recovered orientation error for each fiber bundle. To this aim, they use four different sources of data: synthetic data from Gaussian mixture model, cylinder restricted model, and in vivo data from two different acquisition schemes. RESULTS: Results of their experiments indicate that: (a) it is feasible to apply only a subset of these methods to clinical data sets and (b) it allows one to characterize the performance of each method. In particular, two methods are not feasible to the kind of magnetic resonance diffusion data they test. By the characterization of their systematic behavior, among other conclusions, they report the method which better performs for the estimation of the number of diffusion peaks per voxel, also the method which better estimates the diffusion orientation. CONCLUSIONS: The framework they propose for comparison allows one to effectively characterize and compare the performance of the most frequently used multifiber algorithms under realistic medical settings and realistic signal-to-noise ratio environments. The framework is based on several crossings with a non-orientational bias and different signal models. The results they present are relevant for medical doctors and researchers, interested in the use of the multifiber solution for tractography. PMID- 21978069 TI - A virtual source model for kilo-voltage cone beam CT: source characteristics and model validation. AB - PURPOSE: The purpose of this investigation was to study the source characteristics of a clinical kilo-voltage cone beam CT unit and to develop and validate a virtual source model that could be used for treatment planning purposes. METHODS: We used a previously commissioned full Monte Carlo model and new bespoke software to study the source characteristics of a clinical kilo voltage cone beam CT (CBCT) unit. We identified the main particle sources, their spatial, energy and angular distribution for all the image acquisition presets currently used in our clinical practice. This includes a combination of two energies (100 and 120 kVp), two filters (neutral and bowtie), and eight different x-ray beam apertures. We subsequently built a virtual source model which we validated against full Monte Carlo calculations. RESULTS: We found that the radiation output of the clinical kilo-voltage cone beam CT unit investigated in this study could be reproduced with a virtual model comprising of two sources (target and filtration cone) or three sources (target, filtration cone and bowtie filter) when additional filtration was used. With this model, we accounted for more than 97% of the photons exiting the unit. Each source in our model was characterised by a origin distribution in both X and Y directions, a fluence map, a single energy spectrum for unfiltered beams and a two dimensional energy spectrum for bowtie filtered beams. The percentage dose difference between full Monte Carlo and virtual source model based dose distributions was well within the statistical uncertainty associated with the calculations ( +/- 2%, one standard deviation) in all cases studied. CONCLUSIONS: The virtual source that we developed is accurate in calculating the dose delivered from a commercial kilo voltage cone beam CT unit operating with routine clinical image acquisition settings. Our data have also shown that target, filtration cone, and bowtie filter sources needed to be all included in the model in order to accurately replicate the dose distribution from the clinical radiation beam. PMID- 21978073 TI - Estimating hybridization in the presence of coalescence using phylogenetic intraspecific sampling. AB - BACKGROUND: A well-known characteristic of multi-locus data is that each locus has its own phylogenetic history which may differ substantially from the overall phylogenetic history of the species. Although the possibility that this arises through incomplete lineage sorting is often incorporated in models for the species-level phylogeny, it is much less common for hybridization to also be formally included in such models. RESULTS: We have modified the evolutionary model of Meng and Kubatko (2009) to incorporate intraspecific sampling of multiple individuals for estimation of speciation times and times of hybridization events for testing for hybridization in the presence of incomplete lineage sorting. We have also utilized a more efficient algorithm for obtaining our estimates. Using simulations, we demonstrate that our approach performs well under conditions motivated by an empirical data set for Sistrurus rattlesnakes where putative hybridization has occurred. We further demonstrate that the method is able to accurately detect the signature of hybridization in the data, while this signal may be obscured when other species-tree inference methods that ignore hybridization are used. CONCLUSIONS: Our approach is shown to be powerful in detecting hybridization when it is present. When applied to the Sistrurus data, we find no evidence of hybridization; instead, it appears that putative hybrid snakes in Missouri are most likely pure S. catenatus tergeminus in origin, which has significant conservation implications. PMID- 21978075 TI - A photoactivated artificial muscle model unit: reversible, photoinduced sliding of nanosheets. AB - A novel photoactivated artificial muscle model unit is reported. Here we show that organic/inorganic hybrid nanosheets reversibly slide horizontally on a giant scale and the interlayer spaces in the layered hybrid structure shrink and expand vertically by photoirradiation. The sliding movement of the system on a giant scale is the first example of an artificial muscle model unit having much similarity with that in natural muscle fibrils. In particular, our layered hybrid molecular system exhibits a macroscopic morphological change on a giant scale (~1500 nm) relative to the molecular size of ~1 nm by means of a reversible sliding mechanism. PMID- 21978074 TI - Environmental factors in early childhood are associated with multiple sclerosis: a case-control study. AB - BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) with increasing incidence mainly in high-income countries. One explanation of this phenomenon may be a higher prevalence of allergic and autoimmune diseases in industrialized countries as a consequence of otherwise beneficial advances in sanitation (hygiene hypothesis). We investigated environmental factors in early childhood associated with MS. METHODS: A case-control study was performed of 245 MS patients and 296 population based controls in Berlin. The study participants completed a standardized questionnaire on environmental factors in childhood and youth, including aspects of personal and community hygiene. Multivariable logistic regression analysis was performed to investigate factors in childhood and youth associated with the occurrence of MS. RESULTS: Mean age was 46 years (range, 20-80) in the MS group and 42 years (range 18-80) in the control group, of which 73.9% in the MS and 61.5% in the control group were female. The multivariable analysis showed that having at least two older siblings (OR 0.54; p = 0.05, for individuals with two older siblings compared to individuals without older siblings), attending a day care center (OR 0.5; p = 0.004) and growing up in an urban center with more than 100, 000 inhabitants (OR 0.43; p = 0.009) were factors independently associated with a lower chance for MS. CONCLUSIONS: The hygiene hypothesis may play a role in the occurrence of MS and could explain disease distribution and increasing incidence. PMID- 21978076 TI - Three dimensional model-based analysis of the lenticulostriate arteries and identification of the vessels correlated to the infarct area: preliminary results. AB - BACKGROUND: Small vessel diseases have been studied noninvasively with magnetic resonance imaging. Direct observation or visualization of the connected microvessel to the infarct, however, was not possible due to the limited resolution. Hence, one could not determine whether vessel occlusion or abnormal narrowing is the cause of an infarct. METHODS: In this report, we demonstrate that the small vessel related to the infarct can be detected using ultra-high field (7 T) magnetic resonance imaging and a three dimensional image analysis and modeling technique for microvessels, which thereby enables us to quantify the vessel morphology directly, that is, visualize the vessel that is related to the infarct. We compared vessels of selected stroke patients, who had recovered from stroke, with vessels from typical stroke patients, who had after effects like motor weakness, and age-matched healthy subjects to demonstrate the potential of the technique. RESULTS: The experimental results show that typical stroke patients had overall degradation or loss of small vessels, compared with the selected patients as well as healthy subjects. The selected patients, however, had only minimal loss of vessels, except for one vessel located close to the infarct area. CONCLUSIONS: These preliminary results demonstrated that 7 T magnetic resonance imaging together with a three dimensional image analysis and modeling technique could provide information for detection of the vessel related to the infarct. In addition, three dimensional image analysis and modeling of vessels could further provide quantitative information on the microvessel structures comprising diameter, length and tortuosity. PMID- 21978077 TI - Using linked routinely collected health data to describe prostate cancer treatment in New South Wales, Australia: a validation study. AB - BACKGROUND: Population-based patterns of care studies are important for monitoring cancer care but conducting them is expensive and resource-intensive. Linkage of routinely collected administrative health data may provide an efficient alternative. Our aim was to determine the accuracy of linked routinely collected administrative data for monitoring prostate cancer care in New South Wales (NSW), Australia. METHODS: The NSW Prostate Cancer Care and Outcomes Study (PCOS), a population-based survey of patterns of care for men aged less than 70 years diagnosed with prostate cancer in NSW, was linked to the NSW Cancer Registry, electronic hospital discharge records and Medicare and Pharmaceutical claims data from Medicare Australia. The main outcome measures were treatment with radical prostatectomy, any radiotherapy, external beam radiotherapy, brachytherapy or androgen deprivation therapy, and cancer staging. PCOS data were considered to represent the true treatment status. The sensitivity and specificity of the administrative data were estimated and relevant patient characteristics were compared using chi-squared tests. RESULTS: The validation data set comprised 1857 PCOS patients with treatment information linked to Cancer Registry records. Hospital and Medicare claims data combined described treatment more accurately than either one alone. The combined data accurately recorded radical prostatectomy (96% sensitivity) and brachytherapy (93% sensitivity), but not androgen deprivation therapy (76% sensitivity). External beam radiotherapy was rarely captured (5% sensitivity), but this was improved by including Medicare claims for radiation field setting or dosimetry (86% sensitivity). False positive rates were near 0%. Disease stage comparisons were limited by one-third of cases having unknown stage in the Cancer Registry. Administrative data recorded treatment more accurately for cases in urban areas. CONCLUSIONS: Cancer Registry and hospital inpatient data accurately captured radical prostatectomy and brachytherapy treatment, but not external beam radiotherapy or disease stage. Medicare claims data substantially improved the accuracy with which all major treatments were recorded. These administrative data combined are valid for population-based studies of some aspects of prostate cancer care. PMID- 21978078 TI - High-resolution mapping of a novel genetic locus regulating voluntary physical activity in mice. AB - Both human beings and animals exhibit substantial inter-individual variation in voluntary physical activity, and evidence indicates that a significant component of this variation is because of genetic factors. However, little is known of the genetic basis underlying central regulation of voluntary physical activity in mammals. In this study, using an F(2) intercross population and interval specific congenic strains (ISCS) derived from the C57BL/6J strain and a chromosome 13 substitution strain, C57BL/6J-Chr13A/J/NA/J, we identified a 3.76 Mb interval on chromosome 13 containing 25 genes with a significant impact on daily voluntary wheel running activity in mice. Brain expression and polymorphisms between the C57BL/6J and A/J strains were examined to prioritize candidate genes. As the dopaminergic pathway regulates motor movement and motivational behaviors, we tested its function by examining cocaine-induced locomotor responses in ISCS with different levels of activity. The low-activity ISCS exhibited a significantly higher response to acute cocaine administration than the high-activity ISCS. Expression analysis of key dopamine-related genes (dopamine transporter and D1, D2, D3, D4 and D5 receptors) revealed that expression of D1 receptor was higher in the low-activity ISCS than in the high activity ISCS in both the dorsal striatum and nucleus accumbens. Pathway analysis implicated Tcfap2a, a gene found within the 3.76-Mb interval, involved in the D1 receptor pathway. Using a luciferase reporter assay, we confirmed that the transcriptional factor, Tcfap2a, regulates the promoter activity of the D1 receptor gene. Thus, Tcfap2a is proposed as a candidate genetic regulator of the level of voluntary physical activity through its influence on a dopaminergic pathway. PMID- 21978079 TI - Acetyl-L-carnitine attenuates homocysteine-induced Alzheimer-like histopathological and behavioral abnormalities. AB - Hyperhomocystinemia could induce tau protein hyperphosphorylation, beta-amyloid (Abeta) accumulation, and memory deficits as seen in Alzheimer disease (AD), the most common cause of senile dementia with no effective cure currently. To search for possible treatment for AD, we produced a hyperhomocysteinemia model by vena caudalis injection of homocystine (Hcy) for 2 weeks and studied the effects of acetyl-L-carnitine (ALC) in rats. We found that simultaneous supplement of ALC could improve the Hcy-induced memory deficits remarkably, with attenuation of tau hyperphosphorylation and Abeta accumulation. Supplement of ALC almost abolished the Hcy-induced tau hyperphosphorylation at multiple AD-related sites. Supplementation of ALC also suppressed the phosphorylation of beta-amyloid precursor proteins (APP), which may underlie the reduction of Abeta. Our data suggest that ALC could be a promising candidate for arresting Hcy-induced AD-like pathological and behavioral impairments. PMID- 21978080 TI - Cryobanking of embryoid bodies to facilitate basic research and cell-based therapies. AB - Pluripotent stem cells offer unique opportunities for curing debilitating diseases. However, further comprehensive research is needed to better understand cell signaling during the differentiation of pluripotent cells into different cell lineages and accordingly to develop clinically applicable protocols. One of the limiting steps for differentiation studies is proper culture and expansion of pluripotent stem cells, which is labor intensive, expensive, and requires a great deal of expertise. This limiting step can be overcome by successful banking and distribution of embryoid bodies (EBs), which are aggregates of pluripotent stem cells and typically the starting point of differentiation protocols. The objective of this study was to investigate the feasibility of EB banking by studying survival and functionality of cryopreserved EBs. To this end, EBs were formed by culturing mouse 129 embryonic stem (ES) cells in the absence of leukemia inhibitory factor (LIF) in hanging drops and then subjected to different cryopreservation protocols. In a series of experiments, we first tested the postthaw survival of EBs as a function of dimethylsulfoxide (DMSO) and extracellular trehalose concentrations and cooling rates. Next, we studied the functionality of cryopreserved EBs by assessing their postthaw attachment, growth, and differentiation into various cell types. Higher (>=5%) DMSO concentrations alone or in combination with trehalose (0.1 M and 0.2 M) yielded good postthaw survival rates of >80%, whereas cooling of EBs at 1 degrees C/min in the presence of 5% DMSO +0.1 M trehalose gave the best attachment and growth rates, with differentiation into cell lineages of three germ layers. Taken together, our results suggest that EBs are tolerant to cryopreservation associated stresses and retain their differentiation potential after freezing and thawing. Furthermore, our experiments with dissociated EB cells and nondissociated EBs suggest that the extracellular matrix may play a beneficial role in the cryotolerance of EBs. Overall, our data support the feasibility of EB banking, which would facilitate advancement of cell-based therapies. PMID- 21978081 TI - Neuroinflammation in delirium: a postmortem case-control study. AB - BACKGROUND: Delirium can be hypothesized to be an extreme manifestation of sickness behavior in elderly persons with neurodegenerative disease. The purpose of this study was to investigate whether increased cerebral inflammation with microglial, astrocyte, and cytokine activation exists in patients with delirium compared to nondelirious patients. METHODS: Postmortem brain tissue from 9 cases with delirium was compared to 6 age-matched controls without delirium. Human leukocyte antigen-DR (HLA-DR) and CD68 cell count and glial fibrillary acidic protein (GFAP), interleukin-1beta (IL-1beta), IL-6,beta-amyloid, and tau protein immunoreactivity were determined in hippocampus, frontal cortex, and white matter. RESULTS: There were no significant differences in the patients with delirium compared to the controls with respect to age 73 versus 70.5 years (p=0.72) or dementia (22% versus 0%, p=0.22). Both markers for microglial activity showed significantly higher scores in delirium brain specimens than controls in the total brain score (HLA-DR 129 vs. 20 and CD68 30 vs. 8.5) as well as in the various brain areas separately. The immunoreactivity of astrocyte activity (GFAP) was higher in the total brain score in patients with delirium (5.2 vs. 4.0, p=0.05), but in the various brain areas this was only significant in the dentate gyrus. IL-6 immunoreactivity was higher in patients with delirium in all brain areas and IL-1beta was not detectable. Coexisting infectious disease or dementia did not influence the overall results. CONCLUSIONS: These preliminary study results show an association between human brain activity of microglia, astrocytes, and IL-6 and delirium in elderly patients and add to the accumulating evidence that inflammatory mechanisms are involved in delirium. PMID- 21978082 TI - Intracerebroventricular administration of human umbilical cord blood cells delays disease progression in two murine models of motor neuron degeneration. AB - The lack of effective drug therapies for motor neuron diseases (MND), and in general for all the neurodegenerative disorders, has increased the interest toward the potential use of stem cells. Among the cell therapy approaches so far tested in MND animal models, systemic injection of human cord blood mononuclear cells (HuCB-MNCs) has proven to reproducibly increase, although modestly, the life span of SOD1G93A mice, a model of familial amyotrophic lateral sclerosis (ALS), even if only few transplanted cells were found in the damaged areas. In attempt to improve the potential efficacy of these cells in the central nervous system, we examined the effect and distribution of Hoechst 33258-labeled HuCB MNCs after a single bilateral intracerberoventricular injection in two models of motor neuron degeneration, the transgenic SOD1G93A and wobbler mice. HuCB-MNCs significantly ameliorated symptoms progression in both mouse models and prolonged survival in SOD1G93A mice. They were localized in the lateral ventricles, even 4 months after administration. However, HuCB-MNCs were not found in the spinal cord ventral horns. This evidence strengthens the hypothesis that the beneficial role of transplanted cells is not due to cell replacement but is rather associated with the production and release of circulating protective factors that may act both at the central and/or peripheral levels. In particular, we show that HuCB MNCs release a series of cytokines and chemokines with antiinflammatory properties that could be responsible of the functional improvement of mouse models of motor neuron degenerative disorders. PMID- 21978083 TI - Eye lens in aging and diabetes: effect of quercetin. AB - Old age is accompanied by a number of pathological eye conditions. Cataract is the most common age-related eye complication. Because the lens becomes naturally more opaque over time, aging is the most important risk factor for developing cataract, which is a major cause of blindness in the world. Cataractogenesis is also one of the earliest secondary complications of diabetes mellitus. The lens is a closed system with limited capability to repair or regenerate itself. Current evidence supports the view that cataractogenesis is a multifactorial process. Oxidative stress and its sequelae are clearly involved in the etiology of senile cataract, whereas mechanisms related to glucose toxicity, namely oxidative stress, processes of nonenzymatic glycation, and enhanced polyol pathway contribute significantly to the development of the eye complications under conditions of diabetes. There is an urgent need for inexpensive, nonsurgical approaches to the treatment of cataract. Recently, considerable attention has been devoted to the search for phytochemical therapeutics. Several pharmacological actions of natural flavonoids may operate in preventing cataract because flavonoids are capable of affecting multiple mechanisms or etiological factors responsible for the development of sight-threatening ocular diseases. The flavonol quercetin is the most widely consumed flavonoid in the human diet. In this article, quercetin is reviewed as an agent that could reduce the risk of cataract formation via affecting multiple pathways pertinent to eye lens opacification, including oxidative stress, nonenzymatic glycation, the polyol pathway, lens calpain proteases, and epithelial cell signaling. In addition, the bioavailability of quercetin to the lens is considered. PMID- 21978084 TI - Pinealon increases cell viability by suppression of free radical levels and activating proliferative processes. AB - The synthetic tripeptide pinealon (Glu-Asp-Arg) demonstrates dose-dependent restriction of reactive oxygen species (ROS) accumulation in cerebellar granule cells, neutrophils, and pheochromocytoma (PC12) cells, induced by oxidative stress stimulated by receptor-dependent or -independent processes. At the same time, pinealon decreases necrotic cell death measured by the propidium iodide test. The protective effect of pinealon is accompanied with a delayed time course of ERK 1/2 activation and modification of the cell cycle. Because restriction of ROS accumulation and cell mortality is saturated at lower concentrations, whereas cell cycle modulation continues at higher concentrations of pinealon, one can conclude that besides its known antioxidant activity, pinealon is able to interact directly with the cell genome. PMID- 21978085 TI - Physical training modulates structural and functional features of cell nuclei in type II myofibers of old mice. AB - Aging is associated with a progressive loss of muscle mass, strength, and function, a condition known as sarcopenia, which represents an important risk factor for physical disability in elderly. The mechanisms leading to sarcopenia are still largely unknown, and no specific therapy is presently available to counteract its onset or progress. Many studies have stressed the importance of physical exercise as an effective approach to prevent/limit the age-related muscle mass loss. This study investigated the effects of physical training on pre mRNA pathways in quadriceps and gastrocnemius muscles of old mice by ultrastructural cytochemistry: Structural and in situ molecular features of myonuclei and satellite cell nuclei of type II fibers were compared in exercised versus sedentary old mice, using adult individuals as control. Our results demonstrated that in myonuclei of old mice physical exercise stimulates pre-mRNA transcription, splicing, and export to the cytoplasm, likely increasing muscle protein turnover. In satellite cells, the effect of physical exercise seems to be limited to the reactivation of some factors involved in the transcriptional and splicing apparatus without increasing RNA production, probably making these quiescent cells more responsive to activating stimuli. PMID- 21978086 TI - Delivery of sesamol-loaded solid lipid nanoparticles to the brain for menopause related emotional and cognitive central nervous system derangements. AB - The physicochemical nature of sesamol (logP 1.29; solubility 38.8 mg/mL) substantially enhances its tissue distribution, minimizing its brain delivery. Sesamol-loaded solid lipid nanoparticles (S-SLNs) with an average particle size of 122 nm and an entrapment efficiency of 75.9 +/- 2.91% were developed. Biochemical and behavioral paradigms clearly established the superiority of orally administered S-SLNs. The same was confirmed evidently by scintigraphic images of rabbits administered radiolabeled SLNs and confocal microscopy of brain sections of rats administered similarly prepared SLNs with a fluorescent marker. This study indicates the special importance of using phosphatidylcholine (as co surfactant) in the preparation of SLNs for improving memory deficits. The aim of the present work was to develop sesamol as a therapeutic agent for central nervous system derangements. PMID- 21978087 TI - Effects of music therapy on anxiety of patients with breast cancer after radical mastectomy: a randomized clinical trial. AB - AIM: This paper is a report of a clinical trial of the effects of music therapy on anxiety of female breast cancer patients following radical mastectomy. BACKGROUND: There is insufficient evidence on the effects of music therapy on state anxiety of breast cancer patients following radical mastectomy. METHODS: A Hall's Core, Care, and Cure Model-based clinical trial was conducted in 120 female breast cancer patients from March to November 2009. A randomized controlled design was utilized. The patients were randomly allocated to the experimental group (n = 60) received music therapy in addition to routine nursing care, and the control group (n = 60) only received routine nursing care. A standardized questionnaire and the State Anxiety Inventory were applied. The primary endpoint was the state anxiety score measured at pretest (on the day before radical mastectomy) and at three post-tests (on the day before patients were discharged from hospital, the second and third time of admission to hospital for chemotherapy respectively). RESULTS: The pretest score revealed that the majority of the patients had a moderate level (77.5%) and 15% had severe level of state anxiety. The repeated-measure ancova model analysis indicated that the mean state anxiety score was significantly lower in the experimental group than those in the control group at each of the three post-test measurements. The mean difference between the experimental and control group together with 95% confidence intervals were -4.57 (-6.33, -2.82), -8.91 (-10.75, -7.08) and -9.69 ( 11.52, -7.85) at the 1st post-test, 2nd post-test and 3rd post-test respectively. CONCLUSION: Music therapy is found to have positive effects on decreasing state anxiety score. PMID- 21978089 TI - Excited-state behavior of ortho-phenylenes. AB - The excited-state properties of unsubstituted ortho-phenylene oligomers have been studied using TD-DFT. Calculations of vertical transitions at the helical ground state geometries are in good qualitative agreement with the experimental UV-vis spectra. In the excited state, the spring-like compounds compress; for the longer oligomers, this compression is localized at one end of the oligomer. This behavior explains the unusual experimentally observed hypsochromic shifts in fluorescence spectra with increasing oligomer length. PMID- 21978088 TI - Development of gustatory papillae in the absence of Six1 and Six4. AB - Six family genes encode homeobox transcription factors, and a deficiency in them leads to abnormal structures of the sensory organs. In a previous paper, Six1 was reported to be expressed in the taste bud-bearing lingual papillae of mice, and loss of Six1 affected the development of these gustatory papillae. We show here that embryos lacking both Six1 and Six4 revealed more severe abnormalities than those lacking Six1 alone during morphogenesis of their gustatory papillae. By in situ hybridization, Six4 was shown to be broadly distributed in the epithelium of the lateral lingual swellings at embryonic day (E) 11.5, and in the tongue epithelium, mesenchyme, and muscles at E12.5. From E14, Six4 was similar in expression pattern to Six1, as previously reported. In the fungiform papillae, Six4 was expressed in the epithelium at E14-E16.5. In the circumvallate and foliate papillae, Six4 expression was observed in the trench wall of these papillae at E15.5-P0. Although Six4-deficient mice had no abnormalities, Six1/Six4-deficient mice showed distinct morphological changes: fusion of the lateral lingual swellings was delayed, and the tongue was poorly developed. The primordia of fungiform papillae appeared earlier than those in the wild-type or Six1-deficient mice, and the papillae rapidly increased in size; thus fusion of each papilla was evident. The circumvallate papillae showed severe defects; for example, invagination of the trenches started asymmetrically, which resulted in longer and shorter trenches. The foliate papillae elevated initially, and showed stunted trenches. Therefore, Six1 and Six4 function synergistically to form gustatory papillae during development of the tongue. PMID- 21978090 TI - The emergence and portrayal of obesity in The Irish Times: content analysis of obesity coverage, 1997-2009. AB - Both global obesity prevalence rates and media attention to obesity have increased significantly in recent years. The current study examined the representation of obesity in The Irish Times, from 1997 to 2009. A quantitative content analysis was conducted on 479 articles to examine how the causes, consequences, and solutions to obesity have been portrayed and how obesity has been described. A frame analysis was also conducted to examine the dominant frames over time. It was found that attention to obesity was positively correlated with time, indicating coverage has increased significantly over the period examined. Regarding reported causes and solutions, the behavioral frame has been dominant, though environmental and mixed-frame stories have become more frequent. The presence of the genetic frame was consistently low. The study provides an overview of how the issue is being represented in Ireland's paper of record and informs health communicators of the dominant and trending messages and the implications for individuals' formation of illness representations. PMID- 21978091 TI - Combination of transcranial sonography, olfactory testing, and MIBG myocardial scintigraphy as a diagnostic indicator for Parkinson's disease. AB - BACKGROUND: Appropriate diagnostic biomarkers are useful for improving speed and accuracy of a diagnosis. Substantia nigra (SN) hyperechogenicity visualized by transcranial sonography (TCS), olfactory dysfunction, and the reduced uptake of (123) I-metaiodobenzylguanidine (MIBG) in myocardial scintigraphy have been suggested as potential biomarkers for the identification of Parkinson's disease (PD). OBJECTIVES: To evaluate the diagnostic potential of these tests and to determine whether combining them increases their diagnostic power. METHODS: Subjects were 44 patients with clinically diagnosed PD and 36 healthy controls. TCS of the SN, the odor stick identification test for Japanese (OSIT-J), and MIBG myocardial scintigraphy were conducted. RESULTS: Eleven patients with PD (25%) and four controls (11%) were excluded because of an insufficient acoustic temporal bone window in the TCS. Thus, 33 patients with PD and 32 healthy controls were finally included. The diagnostic sensitivity of TCS, OSIT-J, and MIBG myocardial scintigraphy was 78.8%, 84.8%, and 60.6%, respectively. The specificity of TCS and OSIT-J was 93.8% and 78.1%, respectively. The combination of TCS of the SN and OSIT-J substantially increased the sensitivity to a sufficient level for discriminating patients with PD from controls. CONCLUSION: TCS of the SN and olfactory testing play complementary roles in increasing diagnostic power in PD. As both tests are easy to perform, noninvasive, and inexpensive, the combination of TCS of the SN and olfactory testing may contribute to early and accurate diagnosis of PD. PMID- 21978093 TI - Abstracts of the 37th Annual Meeting of the International Society for Pediatric and Adolescent Diabetes (ISPAD). October 19-22, 2011. Miami Beach, Florida, USA. PMID- 21978094 TI - Fitness costs of neighborhood disruption in translocations of a solitary mammal. AB - Translocation is used to reestablish wild populations of animals, but translocation projects often do not meet their objectives because postrelease mortality of animals is high. One reason for translocation failure is that the behavioral or ecological requirements of released animals are unmet. Maintaining founder-group social relationships during release can affect reestablishment of social species. Solitary territorial species with stable neighbors (restricted dispersal and lifetime occupation of a home range) of the same species may also benefit from the maintenance of these social relationships during translocation. We translocated Stephens' kangaroo rats (Dipodomys stephensi), a solitary species listed as endangered under the U.S. Endangered Species Act, with and without neighboring kangaroo rats. We compared the settlement (establishment of a stable home range) decisions and fitness of kangaroo rats between the 2 treatments. Kangaroo rats translocated with neighbors traveled shorter distances before establishing territories, had higher survival rates, and had significantly higher reproductive success than kangaroo rats translocated without neighbors. Number of offspring was 24-fold higher for kangaroo rats translocated with neighbors than those translocated without neighbors. Differences in behavior following release may partially explain differences in survival between the 2 groups. Immediately following release, animals translocated with neighbors fought less and spent significantly more time foraging and digging burrows than animals translocated without neighbors. Our results indicate that even for solitary species, maintaining relationships among members of a translocated group of animals can influence translocation success. This study is the first empirical demonstration of the fitness consequences of disrupting social relationships among territorial neighbors. PMID- 21978092 TI - A proteomic survey of nonribosomal peptide and polyketide biosynthesis in actinobacteria. AB - Actinobacteria such as streptomycetes are renowned for their ability to produce bioactive natural products including nonribosomal peptides (NRPs) and polyketides (PKs). The advent of genome sequencing has revealed an even larger genetic repertoire for secondary metabolism with most of the small molecule products of these gene clusters still unknown. Here, we employed a "protein-first" method called PrISM (Proteomic Investigation of Secondary Metabolism) to screen 26 unsequenced actinomycetes using mass spectrometry-based proteomics for the targeted detection of expressed nonribosomal peptide synthetases or polyketide synthases. Improvements to the original PrISM screening approach (Nat. Biotechnol. 2009, 27, 951-956), for example, improved de novo peptide sequencing, have enabled the discovery of 10 NRPS/PKS gene clusters from 6 strains. Taking advantage of the concurrence of biosynthetic enzymes and the secondary metabolites they generate, two natural products were associated with their previously "orphan" gene clusters. This work has demonstrated the feasibility of a proteomics-based strategy for use in screening for NRP/PK production in actinomycetes (often >8 Mbp, high GC genomes) versus the bacilli (2-4 Mbp genomes) used previously. PMID- 21978095 TI - A naive Gaussian Bayes classifier for detection of mental activity in gait signature. AB - A probabilistic modelling is presented to detect mental activity from gait signature recorded from healthy subjects. The proposed scheme is based on principal component analysis with reduced feature dimension followed by a naive Gaussian Bayes classifier. The leave-one-out cross-validation shows the detection accuracy of 94% with specificity and sensitivity of 96% and 98.3%, respectively. The research has a potential application in the prevention of elderly risk falls, lie detection and rehabilitation among Parkinson's patients. PMID- 21978096 TI - Carbohydrate-functionalized chitosan fiber for influenza virus capture. AB - The high transmissibility and genetic variability of the influenza virus have made the design of effective approaches to control the infection particularly challenging. The virus surface hemagglutinin (HA) protein is responsible for the viral attachment to the host cell surface via the binding with its glycoligands, such as sialyllactose (SL), and thereby is an attractive target for antiviral designs. Herein we present the facile construction and development of two SL incorporated chitosan-based materials, either as a water-soluble polymer or as a functional fiber, to demonstrate their abilities for viral adhesion inhibition and decontamination. The syntheses were accomplished by grafting a lactoside bearing an aldehyde-functionalized aglycone to the amino groups of chitosan or chitosan fiber followed by the enzymatic sialylation with sialyltransferase. The obtained water-soluble SL-chitosan conjugate bound HA with high affinity and inhibited effectively the viral attachment to host erythrocytes. Moreover, the SL functionalized chitosan fiber efficiently removed the virus from an aqueous medium. The results collectively demonstrate that these potential new materials may function as the virus adsorbents for prevention and control of influenza. Importantly, these materials represent an appealing approach for presenting a protein ligand on a chitosan backbone, which is a versatile molecular platform for biofunctionalization and, thereby, can be used for not only antiviral designs, but also extensive medical development such as diagnosis and drug delivery. PMID- 21978097 TI - Increased expression of tight junctions in ARPE-19 cells under endoplasmic reticulum stress. AB - PURPOSE: To investigate the effects of endoplasmic reticulum (ER) stress on the tight junctions of the retinal pigment epithelial (RPE) cells in vitro. MATERIALS AND METHODS: ER stress was induced in cultured ARPE-19 cells, a human RPE cell line, by exposure to tunicamycin (TM) or to thapsigargin (TG). After 6, 12, 24 and 48 hours of exposure, the expressions of GRP78/Bip (Bip), C/EBP-homologous protein (CHOP), vascular endothelial growth factor (VEGF), zonula occludens (ZO) 1, occludin and claudin-1 were determined by real-time RT-PCR. Immunoblot analysis and/or immunohistochemistry for proteins of tight junctions and ER stress markers, viz., Bip, activating transcription factor (ATF) 6, CHOP, and caspase-4, were performed at 48 hours after the exposure. Enzyme-linked immunosorbent assay was used to determine the concentration of VEGF165. Transepithelial electrical resistance (TER) of the ARPE-19 cells was determined to measure the permeability. RESULTS: The expressions of the mRNAs and/or proteins of Bip, CHOP, ATF6 and caspase-4 were significantly increased in ARPE-19 cells under ER stress induced by TM and TG. The mRNAs of VEGF were also increased by both TM and TG. However, the concentration of VEGF165 was not significantly increased after 48 hours exposure to TM and TG compared to that of the control in the apical chamber medium. The proteins and mRNAs of occludin and claudin-1 were significantly increased by TM and TG, and that of ZO-1 was significantly increased by TG. Immunohistochemistry showed that the staining of ZO-1, occludin and claudin-1 under ER stress was stronger than that of the control. A significant increase of TER was observed after exposure to TM and TG. CONCLUSIONS: The increased expressions of tight junction molecules by TM- or TG exposed ARPE-19 cells indicate that ER stress can alter the function of RPE cells and may be involved in the pathogenesis of age-related macular degeneration. PMID- 21978098 TI - L-Cysteine as a chiral linker in lanthanide-cucurbit[6]uril one-dimensional assemblies. AB - The reaction of neodymium, europium, or terbium nitrate with cucurbit[6]uril (CB6) in the presence of the alpha-amino acid L-cysteine (L-cys) gives the complexes [Nd(L-cys)(CB6)(NO(3))(H(2)O)(4)].2NO(3).10H(2)O (1) and {[Ln(L cys)(CB6)(H(2)O)(5)][Ln(L-cys)(CB6)(NO(3))(H(2)O)(4)]}.5NO(3).22H(2)O with Ln = Eu (2) or Tb (3). 2 and 3 only differ from 1 by the presence of two independent metal ions in slightly different environments. In all cases, each metal atom is bound to the bidentate CB6 and the monodentate L-cys molecules, with the latter being in its zwitterionic form. The ammonium group of L-cys is directed away from CB6 and is involved in ion-dipole and hydrogen bonding interactions with the uncomplexed portal of the neighboring molecule, which gives rise to the formation of chiral one-dimensional assemblies of columnar shape. PMID- 21978099 TI - Gas adsorption properties of the ternary ZnO/CuO/CuCl(2) impregnated activated carbon system for multigas respirator applications assessed through combinatorial methods and dynamic adsorption studies. AB - A ternary library of 64 ZnO/CuO/CuCl(2) impregnated activated carbon samples was synthesized and screened automatically using a combinatorial (combi) method. The ability of the samples to adsorb toxic gases was screened gravimetrically. The stoichiometric ratio of reaction (SRR) between the moles of toxicant and the total moles of impregnant was obtained from the calculated mass increase of the samples after chemisorption, with a high SRR indicating high efficiency of toxicant removal. The combi samples that exhibited good dry SO(2) and NH(3) adsorption were prepared in bulk using the incipient wetness method and were evaluated for multigas respirator function by dynamic adsorption studies of SO(2), NH(3), HCN, and C(6)H(12) gases in either dry or humid conditions at ambient temperature. The bulk samples showed equivalent gas adsorption capacities when exposed to the different challenge gases indicating the value of the combi method for initial screening. Cu(2)Cl(OH)(3) was identified to be a potential multigas adsorbent. PMID- 21978100 TI - Perioperative rehabilitation approaches in those over 75 years with respiratory dysfunction from chronic obstructive pulmonary disease undergoing abdominal tumor surgery. AB - PURPOSE: We report two cases of perioperative rehabilitation for abdominal cancer patients aged 75 years and older with severe chronic obstructive pulmonary disease (COPD). CASE DESCRIPTION: Case 1 was a 75-year-old man with COPD and 52 year history of smoking 30 cigarettes per day. The patient was diagnosed with gastric cancer and scheduled for laparoscopic total gastrectomy. Preoperative forced expiratory volume in 1 second (FEV1) was 0.64 L. He could walk with intermittent rest. Case 2 was an 81-year-old woman with COPD, bronchial asthma and 40-year history of smoking 20 cigarettes per day. She was diagnosed with transverse colon cancer and scheduled for laparoscopic-assisted partial transverse colectomy. Preoperative FEV1 was 0.70 L. She could walk indoors with T cane. RESULTS: All staff started performing tasks simultaneously a week before surgery. Both patients were extubated soon after surgery; they could sit and take deep breaths soon after admission to intensive care unit. They could perform stepping movements early next morning, return to the general ward in the afternoon and started gait training. Because both patients could independently perform activities of daily living, they were discharged on postoperative day 13. CONCLUSION: Comprehensive perioperative rehabilitation appears to be effective in high-risk patients with severe COPD who need surgery for abdominal cancer. PMID- 21978101 TI - Increasing the sensitivity of magnetic resonance spectroscopy and imaging. AB - Nuclear magnetic resonance and magnetic resonance imaging are two of the most important techniques in analytical chemistry and noninvasive medical imaging, respectively. They share a common physical basis, one aspect of which is a low intrinsic sensitivity relative to complementary techniques. Encouragingly, recent advances in physics, chemistry, engineering, and data processing have enabled significant increases in sensitivity, as measured by both increased signal-to noise and reduced data acquisition times, allowing previously unattainable data to be acquired and also new types of experiments to be designed. PMID- 21978102 TI - Modulation of excitability in human primary somatosensory and motor cortex by paired associative stimulation targeting the primary somatosensory cortex. AB - Input from primary somatosensory cortex (S1) to primary motor cortex (M1) is important for high-level motor performance, motor skill learning and motor recovery after brain lesion. This study tested the effects of manipulating S1 excitability with paired associative transcranial stimulation (S1-PAS) on M1 excitability. Given the important role of S1 in sensorimotor integration, we hypothesized that changes in S1 excitability would be directly paralleled by changes in M1 excitability. We applied two established protocols (S1-PAS(LTP) and S1-PAS(LTD) ) to the left S1 to induce long-term potentiation (LTP)-like or long-term depression (LTD)-like plasticity. S1 excitability was assessed by the early cortical components (N20-P25) of the median nerve somatosensory-evoked potential. M1 excitability was assessed by motor-evoked potential amplitude and short-interval intracortical inhibition. Effects of S1-PAS(LTP) were compared with those of a PAS(LTP) protocol targeting the left M1 (M1-PAS(LTP) ). S1 PAS(LTP) and S1-PAS(LTD) did not result in significant modifications of S1 or M1 excitability at the group level due to substantial interindividual variability. The individual S1-PAS-induced changes in S1 and M1 excitability showed no correlation. Furthermore, the individual changes in S1 and M1 excitability induced by S1-PAS(LTP) did not correlate with changes in M1 excitability induced by M1-PAS(LTP) . This demonstrates that the effects of S1 PAS in S1 are variable across individuals and, within a given individual, unrelated to those induced by S1-PAS or M1-PAS in M1. Potentially, this extends the opportunities of therapeutic PAS applications because M1-PAS 'non-responders' may well respond to S1-PAS. PMID- 21978106 TI - A novel splice variant of the stem cell marker LGR5/GPR49 is correlated with the risk of tumor-related death in soft-tissue sarcoma patients. AB - BACKGROUND: The human leucine-rich, repeat-containing G protein-coupled receptor (LGR) 5, also called GPR49, is a marker of stem cells in adult intestinal epithelium, stomach and hair follicles. LGR5/GPR49 is overexpressed in tumors of the colon, ovary and liver and in basal cell carcinomas. Moreover, an expression in skeletal muscle tissues was also detected. However, there has been no investigation regarding the expression and function of LGR5/GPR49 in soft-tissue sarcomas (STS) yet. METHODS: Seventy-seven frozen tumor samples from adult STS patients were studied using quantitative real-time TaqManTM PCR analysis. The mRNA levels of wild type LGR5/GPR49 and a newly identified splice variant of LGR5/GPR49 lacking exon 5 (that we called GPR49Delta5) were quantified. RESULTS: A low mRNA expression level of GPR49Delta5, but not wild type LGR5/GPR49, was significantly correlated with a poor prognosis for the disease-associated survival of STS patients (RR = 2.6; P = 0.026; multivariate Cox's regression hazard analysis). Furthermore, a low mRNA expression level of GPR49Delta5 was associated with a shorter recurrence-free survival (P = 0.043). However, tumor onset in patients with a lower expression level of GPR49Delta5 mRNA occurred 7.5 years later (P = 0.04) than in patients with a higher tumor level of GPR49Delta5 mRNA. CONCLUSION: An attenuated mRNA level of the newly identified transcript variant GPR49Delta5 is a negative prognostic marker for disease-associated and recurrence-free survival in STS patients. Additionally, a lower GPR49Delta5 mRNA level is associated with a later age of tumor onset. A putative role of GPR49Delta5 expression in tumorigenesis and tumor progression of soft tissue sarcomas is suggested. PMID- 21978107 TI - The economic disease burden of measles in Japan and a benefit cost analysis of vaccination, a retrospective study. AB - BACKGROUND: During 1999-2003, Japan experienced a series of measles epidemics, and in Action Plans to Control Measles and the Future Problems, it was proposed that infants be immunized soon after their one-year birthday.In this study, we attempted to estimate the nationwide economic disease burden of measles based on clinical data and the economic effectiveness of this proposal using the benefit cost ratio. METHODS: Our survey target was measles patients treated at Chiba Nishi general hospital from January 1999 to September 2001. Two hundred ninety one cases were extracted from the database. The survey team composed of 3 pediatricians and 1 physician from Chiba-Nishi general hospital examined patient files and obtained additional information by telephone interview.We analyzed data based on a static model, which assumed that the number of measles patients would be zero after 100% coverage of single-antigen measles vaccine.Costs were defined as the direct cost for measles treatment, vaccination and transportation and the indirect cost of workdays lost due to the nursing of patients, hospital visits for vaccination or nursing due to adverse reactions. Benefits were defined as savings on direct and indirect costs. Based on these definitions, we estimated the nationwide costs of treatment and vaccination. RESULTS: Using our static model, the nationwide total cost for measles treatment was estimated to be US$ 404 million, while the vaccination cost was US$165 million. The benefit cost ratio of the base case was 2.48 and ranged from 2.21 to 4.97 with sensitivity analysis. CONCLUSIONS: Although the model has some limitations, we conclude that the policy of immunizing infants soon after their one-year birthday is economically effective. PMID- 21978108 TI - Global oral health inequities. PMID- 21978109 TI - Oral squamous cell carcinoma and 'chewing betel quid'. PMID- 21978110 TI - X-ray computed tomography: advances in image formation. PMID- 21978111 TI - Noise properties of grating-based x-ray phase contrast computed tomography. AB - PURPOSE: To investigate the properties of tomographic grating-based phase contrast imaging with respect to its noise power spectrum and the energy dependence of the achievable contrast to noise ratio. METHODS: Tomographic simulations of an object with 11 cm diameter constituted of materials of biological interest were conducted at different energies ranging from 25 to 85 keV by using a wave propagation approach. Using a Monte Carlo simulation of the x ray attenuation within the object, it is verified that the simulated measurement deposits the same dose within the object at each energy. RESULTS: The noise in reconstructed phase contrast computed tomography images shows a maximum at low spatial frequencies. The contrast to noise ratio reaches a maximum around 45 keV for the simulated object. The general dependence of the contrast to noise on the energy appears to be independent of the material. Compared with reconstructed absorption contrast images, the reconstructed phase contrast images show sometimes better, sometimes worse, and sometimes similar contrast to noise, depending on the material and the energy. CONCLUSIONS: Phase contrast images provide additional information to the conventional absorption contrast images and might thus be useful for medical applications. However, the observed noise power spectrum in reconstructed phase contrast images implies that the usual trade-off between noise and resolution is less efficient for phase contrast imaging compared with absorption contrast imaging. Therefore, high-resolution imaging is a strength of phase contrast imaging, but low-resolution imaging is not. This might hamper the clinical application of the method, in cases where a low spatial resolution is sufficient for diagnosis. PMID- 21978112 TI - A constrained, total-variation minimization algorithm for low-intensity x-ray CT. AB - PURPOSE: The authors developed an iterative image-reconstruction algorithm for application to low-intensity computed tomography projection data, which is based on constrained, total-variation (TV) minimization. The algorithm design focuses on recovering structure on length scales comparable to a detector bin width. METHODS: Recovering the resolution on the scale of a detector bin requires that pixel size be much smaller than the bin width. The resulting image array contains many more pixels than data, and this undersampling is overcome with a combination of Fourier upsampling of each projection and the use of constrained, TV minimization, as suggested by compressive sensing. The presented pseudocode for solving constrained, TV minimization is designed to yield an accurate solution to this optimization problem within 100 iterations. RESULTS: The proposed image reconstruction algorithm is applied to a low-intensity scan of a rabbit with a thin wire to test the resolution. The proposed algorithm is compared to filtered backprojection (FBP). CONCLUSIONS: The algorithm may have some advantage over FBP in that the resulting noise level is lowered at equivalent contrast levels of the wire. PMID- 21978113 TI - Cone-beam artifact evaluation of the factorization method. AB - PURPOSE: The authors investigate the CB artifact behavior of the factorization approach recently suggested for image reconstruction in circular cone-beam computed tomography. This investigation is carried out in a typical C-arm geometry and involves simulated data and for the first time also phantom and clinical CB data acquired with a commercially available angiographic system. METHODS: The CB artifact level is first measured using quantitative figures-of merit that are computed from the reconstructions of the mathematical FORBILD head phantom and of a modified disk phantom. The authors then show reconstructions from a physical thorax phantom and clinical head data sets for a visual assessment of image quality. The performance of the factorization method is primarily compared to that of short-scan FDK, but the authors also show the results obtained with the full-scan FDK and the virtual PI-line BPF method for the simulation studies, as a benchmark. RESULTS: Quantitatively, the FORBILD head phantom reconstructions of both FDK methods show a spatially averaged bias of up to 1.2% in the axial slices about 9 cm away from the plane of the scan, which is placed 4 cm below the central slice through the phantom. The artifact level for the short-scan FDK method and the virtual PI-line BPF method noticeably depends on the scan orientation. The factorization approach can significantly reduce both, this dependency as well as the reconstruction bias. It also shows visually an improved quality of the clinical images compared to short-scan FDK, particularly close to the spine and in the subcranial regions of the clinical data sets. CONCLUSIONS: The factorization approach comes with noticeably lower reconstruction bias than the FDK methods and is least sensitive to the scan orientation among all considered short-scan methods. The data inconsistencies contained in the real data sets, such as scatter, beam hardening, or data truncation, show only little impact on the factorization results. Hence, in both, reconstructions from real and simulated data, the factorization method yields better image quality than short-scan FDK, albeit at the cost of some slight, directed high-frequency artifacts that are mostly visible in axial slices. PMID- 21978114 TI - Fluence field optimization for noise and dose objectives in CT. AB - PURPOSE: Selecting the appropriate imaging technique in computed tomography (CT) inherently involves balancing the tradeoff between image quality and imaging dose. Modulation of the x-ray fluence field, laterally across the beam, and independently for each projection, may potentially meet user-prescribed, regional image quality objectives, while reducing radiation to the patient. The proposed approach, called fluence field modulated CT (FFMCT), parallels the approach commonly used in intensity-modulated radiation therapy (IMRT), except "image quality plans" replace the "dose plans" of IMRT. This work studies the potential noise and dose benefits of FFMCT via objective driven optimization of fluence fields. METHODS: Experiments were carried out in simulation. Image quality plans were defined by specifying signal-to-noise ratio (SNR) criteria for regions of interest (ROIs) in simulated cylindrical and oblong water phantoms, and an anthropomorphic phantom with bone, air, and water equivalent regions. X-ray fluence field patterns were generated using a simulated annealing optimization method that attempts to achieve the spatially-dependent prescribed SNR criteria in the phantoms while limiting dose (to the volume or subvolumes). The resulting SNR and dose distributions were analyzed and compared to results using a bowtie filtered fluence field. RESULTS: Compared to using a fixed bowtie filtered fluence, FFMCT achieved superior agreement with the target image quality objectives, and resulted in integral dose reductions ranging from 39 to 52%. Prioritizing dose constraints for specific regions of interest resulted in a preferential reduction of dose to those regions with some tradeoff in SNR, particularly where the target low dose regions overlapped with regions where high SNR was prescribed. The method appeared fairly robust under increased complexity and heterogeneity of the object structure. CONCLUSIONS: These results support that FFMCT has the potential to meet prescribed image quality objectives, while decreasing radiation exposure to the patient. Tradeoffs between SNR and dose may not be eliminated, but might be more efficiently managed using FFMCT. PMID- 21978115 TI - Automated assessment of low contrast sensitivity for CT systems using a model observer. AB - PURPOSE: Low contrast sensitivity of CT scanners is regularly assessed by subjective scoring of low contrast detectability within phantom CT images. Since in these phantoms low contrast objects are arranged in known fixed patterns, subjective rating of low contrast visibility might be biased. The purpose of this study was to develop and validate a software for automated objective low contrast detectability based on a model observer. METHODS: Images of the low contrast module of the Catphan 600 phantom were used for the evaluation of the software. This module contains two subregions: the supraslice region with three groups of low contrast objects (each consisting of nine circular objects with diameter 2-15 mm and contrast 0.3, 0.5, and 1.0%, respectively) and the subslice region with three groups of four circular objects each (diameter 3-9 mm; contrast 1.0%). The software method offered automated determination of low contrast detectability using a NPWE (nonprewhitening matched filter with an eye filter) model observer for the supraslice region. The model observer correlated templates of the low contrast objects with the acquired images of the Catphan phantom and a discrimination index d' was calculated. This index was transformed into a proportion correct (PC) value. In the two-alternative forced choice (2-AFC) experiments used in this study, a PC >= 75% was proposed as a threshold to decide whether objects were visible. As a proof of concept, influence of kVp (between 80 and 135 kV), mAs (25-200 mAs range) and reconstruction filter (four filters, two soft and two sharp) on low contrast detectability was investigated. To validate the outcome of the software in a qualitative way, a human observer study was performed. RESULTS: The expected influence of kV, mAs and reconstruction filter on image quality are consistent with the results of the proposed automated model. Higher values for d' (or PC) are found with increasing mAs or kV values and for the soft reconstruction filters. For the highest contrast group (1%), PC values were fairly above 75% for all object diameters >2 mm, for all conditions. For the 0.5% contrast group, the same behavior was observed for object diameters >3 mm for all conditions. For the 0.3% contrast group, PC values were higher than 75% for object diameters >6 mm except for the series acquired at the lowest dose (25 mAs), which gave lower PC values. In the human observer study similar trends were found. CONCLUSIONS: We have developed an automated method to objectively investigate image quality using the NPWE model in combination with images of the Catphan phantom low contrast module. As a first step, low contrast detectability as a function of both acquisition and reconstruction parameter settings was successfully investigated with the software. In future work, this method could play a role in image reconstruction algorithms evaluation, dose reduction strategies or novel CT technologies, and other model observers may be implemented as well. PMID- 21978116 TI - Iterative correction of beam hardening artifacts in CT. AB - PURPOSE: To reduce beam hardening artifacts in CT in case of an unknown x-ray spectrum and unknown material properties. METHODS: The authors assume that the object can be segmented into a few materials with different attenuation coefficients, and parameterize the spectrum using a small number of energy bins. The corresponding unknown spectrum parameters and material attenuation values are estimated by minimizing the difference between the measured sinogram data and a simulated polychromatic sinogram. Three iterative algorithms are derived from this approach: two reconstruction algorithms IGR and IFR, and one sinogram precorrection method ISP. RESULTS: The methods are applied on real x-ray data of a high and a low-contrast phantom. All three methods successfully reduce the cupping artifacts caused by the beam polychromaticity in such a way that the reconstruction of each homogeneous region is to good accuracy homogeneous, even in case the segmentation of the preliminary reconstruction image is poor. In addition, the results show that the three methods tolerate relatively large variations in uniformity within the segments. CONCLUSIONS: We show that even without prior knowledge about materials or spectrum, effective beam hardening correction can be obtained. PMID- 21978117 TI - Dynamic CT technique for assessment of wrist joint instabilities. AB - PURPOSE: To develop a 4D [three-dimensional (3D) + time] CT technique to capture high spatial and temporal resolution images of wrist joint motion so that dynamic joint instabilities can be detected before the development of static joint instability and onset of osteoarthritis (OA). METHODS: A cadaveric wrist was mounted onto a custom motion simulator and scanned with a dual source CT scanner during radial-ulnar deviation. A dynamic 4D CT technique was utilized to reconstruct images at 20 equidistant time points from one motion cycle. 3D images of carpal bones were generated using volume rendering techniques (VRT) at each of the 20 time points and then 4D movies were generated to depict the dynamic joint motion. The same cadaveric wrist was also scanned after cutting all portions of the scapholunate interosseus ligament to simulate scapholunate joint instability. Image quality were assessed on an ordinal scale (1-4, 4 being excellent) by three experienced orthopedic surgeons (specialized in hand surgery) by scoring 2D axial images. Dynamic instability was evaluated by the same surgeons by comparing the two 4D movies of joint motion. Finally, dose reduction was investigated using the cadaveric wrist by scanning at different dose levels to determine the lowest radiation dose that did not substantially alter diagnostic image quality. RESULTS: The mean image quality scores for dynamic and static CT images were 3.7 and 4.0, respectively. The carpal bones, distal radius and ulna, and joint spaces were clearly delineated in the 3D VRT images, without motion blurring or banding artifacts, at all time points during the motion cycle. Appropriate viewing angles could be interactively selected to view any articulating structure using different 3D processing techniques. The motion of each carpal bone and the relative motion among the carpal bones were easily observed in the 4D movies. Joint instability was correctly and easily detected in the scan performed after the ligament was cut by observing the relative motion between the scaphoid and lunate bones. Diagnostic capability was not sacrificed with a volume CT dose index (CTDI(vol)) as low as 18 mGy for the whole scan, with estimated skin dose of approximately 33 mGy, which is much lower than the threshold for transient skin erythema (2000 mGy). CONCLUSIONS: The proposed dynamic 4D CT imaging technique generated high spatial and high temporal resolution images without requiring periodic joint motion. Preliminary results from this cadaveric study demonstrate the feasibility of detecting joint instability using this technique. PMID- 21978118 TI - Confidence intervals for performance assessment of linear observers. AB - PURPOSE: This work seeks to develop exact confidence interval estimators for figures of merit that describe the performance of linear observers, and to demonstrate how these estimators can be used in the context of x-ray computed tomography (CT). The figures of merit are the receiver operating characteristic (ROC) curve and associated summary measures, such as the area under the ROC curve. Linear computerized observers are valuable for optimization of parameters associated with image reconstruction algorithms and data acquisition geometries. They provide a means to perform assessment of image quality with metrics that account not only for shift-variant resolution and nonstationary noise but that are also task-based. METHODS: We suppose that a linear observer with fixed template has been defined and focus on the problem of assessing the performance of this observer for the task of deciding if an unknown lesion is present at a specific location. We introduce a point estimator for the observer signal-to noise ratio (SNR) and identify its sampling distribution. Then, we show that exact confidence intervals can be constructed from this distribution. The sampling distribution of our SNR estimator is identified under the following hypotheses: (i) the observer ratings are normally distributed for each class of images and (ii) the variance of the observer ratings is the same for each class of images. These assumptions are, for example, appropriate in CT for ratings produced by linear observers applied to low-contrast lesion detection tasks. RESULTS: Unlike existing approaches to the estimation of ROC confidence intervals, the new confidence intervals presented here have exactly known coverage probabilities when our data assumptions are satisfied. Furthermore, they are applicable to the most commonly used ROC summary measures, and they may be easily computed (a computer routine is supplied along with this article on the Medical Physics Website). The utility of our exact interval estimators is demonstrated through an image quality evaluation example using real x-ray CT images. Also, strong robustness is shown to potential deviations from the assumption that the ratings for the two classes of images have equal variance. Another aspect of our interval estimators is the fact that we can calculate their mean length exactly for fixed parameter values, which enables precise investigations of sampling effects. We demonstrate this aspect by exploring the potential reduction in statistical variability that can be gained by using additional images from one class, if such images are readily available. We find that when additional images from one class are used for an ROC study, the mean AUC confidence interval length for our estimator can decrease by as much as 35%. CONCLUSIONS: We have shown that exact confidence intervals can be constructed for ROC curves and for ROC summary measures associated with fixed linear computerized observers applied to binary discrimination tasks at a known location. Although our intervals only apply under specific conditions, we believe that they form a valuable tool for the important problem of optimizing parameters associated with image reconstruction algorithms and data acquisition geometries, particularly in x-ray CT. PMID- 21978120 TI - Beam shaper with optimized dose utility for helical cone-beam CT. AB - PURPOSE: To develop a new design of an x-ray beam shaper for helical computed tomography (CT) that increases the dose utilization. METHODS: For typical reconstruction algorithms in helical CT, different data are utilized with different weights during back-projection. In particular, data of the outer detector rows, i.e., data acquired at larger cone-angles, are used with smaller weights than data from the central detector rows. Given this spatial variation of the back-projection weights, a beam shaper is designed that creates a spatial variation of the noise variance across the detector such that the used back projection weights are the statistically optimal weights. The effect of the beam shaper on the reconstructed images are studied using simulated data and analytical as well as iterative reconstruction algorithms. RESULTS: For a particular analytical reconstruction algorithm, we obtain an average reduction of the noise by 12% within the object. In combination with iterative reconstruction, the beam shaper creates an insensitivity to patient motion without introducing any heuristic data weighting. CONCLUSIONS: The demonstrated noise reduction by 12% is equivalent to a possible dose saving of 25%. This dose saving can be achieved by a relatively minor hardware change in the CT system and it does not require any changes to the reconstruction algorithm. PMID- 21978119 TI - Gel'fand-Graev's reconstruction formula in the 3D real space. AB - PURPOSE: Gel'fand and Graev performed classical work on the inversion of integral transforms in different spaces [Gel'fand and Graev, Funct. Anal. Appl. 25(1) 1-5 (1991)]. This paper discusses their key results for further research and development. METHODS: The Gel'fand-Graev inversion formula reveals a fundamental relationship between projection data and the Hilbert transform of an image to be reconstructed. This differential backprojection (DBP)/backprojection filtration (BPF) approach was rediscovered in the CT field, and applied in important applications such as reconstruction from truncated projections, interior tomography, and limited-angle tomography. Here the authors present the Gel'fand Graev inversion formula in a 3D setting assuming the 1D x-ray transform. RESULTS: The pseudodifferential operator is a powerful theoretical tool. There is a fundamental mathematical link between the Gel'fand-Graev formula and the DBP (or BPF) approach in the case of the 1D x-ray transform in a 3D real space. CONCLUSIONS: This paper shows the power of mathematics for tomographic imaging and the value of a pure theoretical finding, which may appear quite irrelevant to daily healthcare at the first glance. PMID- 21978121 TI - FBP and BPF reconstruction methods for circular X-ray tomography with off-center detector. AB - PURPOSE: Circular scanning with an off-center planar detector is an acquisition scheme that allows to save detector area while keeping a large field of view (FOV). Several filtered back-projection (FBP) algorithms have been proposed earlier. The purpose of this work is to present two newly developed back projection filtration (BPF) variants and evaluate the image quality of these methods compared to the existing state-of-the-art FBP methods. METHODS: The first new BPF algorithm applies redundancy weighting of overlapping opposite projections before differentiation in a single projection. The second one uses the Katsevich-type differentiation involving two neighboring projections followed by redundancy weighting and back-projection. An averaging scheme is presented to mitigate streak artifacts inherent to circular BPF algorithms along the Hilbert filter lines in the off-center transaxial slices of the reconstructions. The image quality is assessed visually on reconstructed slices of simulated and clinical data. Quantitative evaluation studies are performed with the Forbild head phantom by calculating root-mean-squared-deviations (RMSDs) to the voxelized phantom for different detector overlap settings and by investigating the noise resolution trade-off with a wire phantom in the full detector and off-center scenario. RESULTS: The noise-resolution behavior of all off-center reconstruction methods corresponds to their full detector performance with the best resolution for the FDK based methods with the given imaging geometry. With respect to RMSD and visual inspection, the proposed BPF with Katsevich-type differentiation outperforms all other methods for the smallest chosen detector overlap of about 15 mm. The best FBP method is the algorithm that is also based on the Katsevich type differentiation and subsequent redundancy weighting. For wider overlap of about 40-50 mm, these two algorithms produce similar results outperforming the other three methods. The clinical case with a detector overlap of about 17 mm confirms these results. CONCLUSIONS: The BPF-type reconstructions with Katsevich differentiation are widely independent of the size of the detector overlap and give the best results with respect to RMSD and visual inspection for minimal detector overlap. The increased homogeneity will improve correct assessment of lesions in the entire field of view. PMID- 21978122 TI - CT image reconstruction with half precision floating-point values. AB - PURPOSE: Analytic CT image reconstruction is a computationally demanding task. Currently, the even more demanding iterative reconstruction algorithms find their way into clinical routine because their image quality is superior to analytic image reconstruction. The authors thoroughly analyze a so far unconsidered but valuable tool of tomorrow's reconstruction hardware (CPU and GPU) that allows implementing the forward projection and backprojection steps, which are the computationally most demanding parts of any reconstruction algorithm, much more efficiently. METHODS: Instead of the standard 32 bit floating-point values (float), a recently standardized floating-point value with 16 bit (half) is adopted for data representation in image domain and in rawdata domain. The reduction in the total data amount reduces the traffic on the memory bus, which is the bottleneck of today's high-performance algorithms, by 50%. In CT simulations and CT measurements, float reconstructions (gold standard) and half reconstructions are visually compared via difference images and by quantitative image quality evaluation. This is done for analytical reconstruction (filtered backprojection) and iterative reconstruction (ordered subset SART). RESULTS: The magnitude of quantization noise, which is caused by a reduction in the data precision of both rawdata and image data during image reconstruction, is negligible. This is clearly shown for filtered backprojection and iterative ordered subset SART reconstruction. In filtered backprojection, the implementation of the backprojection should be optimized for low data precision if the image data are represented in half format. In ordered subset SART image reconstruction, no adaptations are necessary and the convergence speed remains unchanged. CONCLUSIONS: Half precision floating-point values allow to speed up CT image reconstruction without compromising image quality. PMID- 21978123 TI - Trade-offs between effectiveness and efficiency in stroke rehabilitation. AB - BACKGROUND: Most stroke research has studied rehabilitation effectiveness and rehabilitation efficiency separately and not investigated the potential trade offs between these two indices of rehabilitation. AIMS: To determine whether there is a trade-off between independent factors of rehabilitation effectiveness and rehabilitation efficiency. METHODS: Using a retrospective cohort study design, we studied all stroke patients (n = 2810) from two sub-acute rehabilitation hospitals from 1996 to 2005, representing 87.5% of national bed years during the same period. RESULTS: Independent predictors of poorer rehabilitation effectiveness and log rehabilitation efficiency were * older age * race-ethnicity * caregiver availability * ischemic stroke * longer time to admission * dementia * admission Barthel Index score, and * length of stay. Rehabilitation effectiveness was lower in females, and the gender differences were significantly lower in those aged <=70 years (beta -4.7 (95% confidence interval -7.4 to -2.0)). There were trade-offs between effectiveness and efficiency with respect to admission Barthel Index score and length of stay. An increase of 10 in admission Barthel Index score predicted an increase of 3.6% (95% confidence interval 3.2-4.0) in effectiveness but a decrease of 0.04 (95% confidence interval -0.05 to -0.02) in log efficiency (a reduction of efficiency by 1.0 per 30 days). An increase in log length of stay by 1 (length of stay of 2.7 days) predicted an increase of 8.0% (95% confidence interval 5.7-10.3) in effectiveness but a decrease of 0.82 (95% confidence interval -0.90 to -0.74) in log efficiency (equivalent to a reduction in efficiency by 2.3 per 30 days). For optimal rehabilitation effectiveness and rehabilitation efficiency, the admission Barthel Index score was 30-62 and length of stay was 37-41 days. CONCLUSIONS: There are trade-offs between effectiveness and efficiency during inpatient sub acute stroke rehabilitation with respect to admission functional status and length of stay. PMID- 21978125 TI - Directed evolution of sortase A mutants with altered substrate selectivity profiles. AB - The ligation of two polypeptides in a chemoselective manner by the bacterial transpeptidase sortase A has become a versatile tool for protein engineering approaches. When sortase-mediated ligation is used for protein semisynthesis, up to four mutations resulting from the strict requirement of the LPxTG sorting motif are introduced into the target protein. Here we report the directed evolution of a mutant sortase A that possesses broad substrate selectivity. A phage-display screen of a mutant sortase library that was randomized in the substrate recognition loop was used to isolate this mutant. The altered substrate selectivity represents a gain-of-function that was exploited for the traceless semisynthesis of histone H3. Our report is a decisive step toward a platform of engineered sortases with distinct ligation properties that will conceivably allow for more versatile assemblies of modified proteins in biotechnological approaches. PMID- 21978124 TI - Molecular characterization and evolution of a gene family encoding male-specific reproductive proteins in the African malaria vector Anopheles gambiae. AB - BACKGROUND: During copulation, the major Afro-tropical malaria vector Anopheles gambiae s.s. transfers male accessory gland (MAG) proteins to females as a solid mass (i.e. the "mating plug"). These proteins are postulated to function as important modulators of female post-mating responses. To understand the role of selective forces underlying the evolution of these proteins in the A. gambiae complex, we carried out an evolutionary analysis of gene sequence and expression divergence on a pair of paralog genes called AgAcp34A-1 and AgAcp34A-2. These encode MAG-specific proteins which, based on homology with Drosophila, have been hypothesized to play a role in sperm viability and function. RESULTS: Genetic analysis of 6 species of the A. gambiae complex revealed the existence of a third paralog (68-78% of identity), that we named AgAcp34A-3. FISH assays showed that this gene maps in the same division (34A) of chromosome-3R as the other two paralogs. In particular, immuno-fluorescence assays targeting the C-terminals of AgAcp34A-2 and AgAcp34A-3 revealed that these two proteins are localized in the posterior part of the MAG and concentrated at the apical portion of the mating plug. When transferred to females, this part of the plug lies in proximity to the duct connecting the spermatheca to the uterus, suggesting a potential role for these proteins in regulating sperm motility. AgAcp34A-3 is more polymorphic than the other two paralogs, possibly because of relaxation of purifying selection. Since both unequal crossing-over and gene conversion likely homogenized the members of this gene family, the interpretation of the evolutionary patterns is not straightforward. Although several haplotypes of the three paralogs are shared by most A. gambiae s.l. species, some fixed species-specific replacements (mainly placed in the N- and C-terminal portions of the secreted peptides) were also observed, suggesting some lineage-specific adaptation. CONCLUSIONS: Progress in understanding the signaling cascade in the A. gambiae reproductive pathway will elucidate the interaction of this MAG-specific protein family with their female counterparts. This knowledge will allow a better evaluation of the relative importance of genes involved in the reproductive isolation and fertility of A. gambiae species and could help the interpretation of the observed evolutionary patterns. PMID- 21978126 TI - Electrophilicities of trans-beta-nitrostyrenes. AB - The kinetics of the reactions of the trans-beta-nitrostyrenes 1a-f with the acceptor-substituted carbanions 2a-h have been determined in dimethyl sulfoxide solution at 20 degrees C. The resulting second-order rate constants were employed to determine the electrophile-specific reactivity parameters E of the trans-beta-nitrostyrenes according to the correlation equation log k(2)(20 degrees C) = s(N)(N + E). The E parameters range from -12 to -15 on our empirical electrophilicity scale (www.cup.lmu.de/oc/mayr/DBintro.html). The second-order rate constants for the reactions of trans-beta-nitrostyrenes with some enamines were measured and found to agree with those calculated from the electrophilicity parameters E determined in this work and the previously published N and s(N) parameters for enamines. PMID- 21978127 TI - The molecular epidemiology of equine influenza in Ireland from 2007-2010 and its international significance. AB - REASONS FOR PERFORMING THE STUDY: Antigenic and genetic drift of equine influenza (EI) virus is monitored annually by the Expert Surveillance Panel (ESP), which make recommendations on the need to update vaccines. Surveillance programmes are essential for this process to operate effectively and to decrease the risk of disease spread through the international movement of subclinically infected vaccinated horses. Not only is surveillance necessary to inform vaccine companies which strains are in circulation, but it serves as an early warning system for horse owners, trainers and veterinary clinicians, facilitating the implementation of appropriate prophylactic and control measures. OBJECTIVE: To summarise the genetic analysis of EI viruses detected in Ireland from June 2007 to January 2010. METHODS: The HA1 gene of 18 viruses was sequenced and phylogenetic analysis undertaken. RESULTS: All viruses belonged to the Florida sublineage of the American lineage. Clade 2 viruses predominated up to 2009. The viruses identified on 4 premises in 2007 displayed 100% nucleotide identity to A/eq/Richmond/1/07, the current clade 2 prototype. The first clade 1 virus was identified in November 2009 and, thereafter, clade 1 viruses were responsible for all the outbreaks identified. The Irish clade 1 viruses differ from the clade 1 virus responsible for the EI outbreaks in Japan and Australia in 2007. No virus of the Eurasian lineage was isolated during this surveillance period. CONCLUSIONS: In 2010 the ESP recommended that the vaccines should not include a H7N7 virus or a H3N8 virus of the Eurasian lineage but that they should contain both a clade 1 and clade 2 virus of the Florida sublineage. The surveillance data presented here support these recommendations and indicate that they are epidemiologically relevant. POTENTIAL RELEVANCE: These data also serve as a scientific basis for investigating the source of epizootics and outbreaks both nationally and internationally. PMID- 21978128 TI - Mother-daughter communication about sex: the influence of authoritative parenting style. AB - Parent-child communication about sex has been shown to delay sexual activity and increase contraceptive and condom use. The influence of authoritative parenting style and mothers' perception of daughters' risk on communication about sex was examined in this study. Mothers in a random sample (n=283) with daughters aged 9 15 years were mailed surveys asking about communication with their daughters regarding 11 sex-related topics. Multivariate linear regression was used to assess the influence of authoritative parenting style and mothers' perceptions of risk on the number of topics communicated about and age of the daughter at time of communication for a variety of sexual health communication topics. Authoritative parenting style was related to the number of topics communicated about and was a predictor of age of daughter at the time of communication about sexual intercourse, menstruation, dating/relationships, sexually transmitted diseases (STDs), HIV/AIDS, alcohol, contraceptives, and abstinence, while perceptions of risk were not significant influencers of age at the time of communication for any topics. This research points to the importance of parenting style in determining the timing of parent-child communication about sexual and other risk behaviors. PMID- 21978129 TI - Increased plasma levels of total homocysteine but not asymmetric dimethylarginine in Hispanic subjects with ischemic stroke FREC-VI sub-study. AB - BACKGROUND AND PURPOSE: Despite sharing some metabolic and pathological mechanisms, the reported association between total homocysteine (tHcy), asymmetric dimethylarginine (ADMA) and stroke remains controversial, particularly in Hispanic populations from developing countries in which genetic, socioeconomic, and nutritional factors are different to those described in developed countries. Our objectives were to determine the relationships of these factors to stroke and to each other independent of other cardiovascular risk factors, and to explore potential sex differences. METHODS: This national (Colombia) multicenter case-control study included 238 cases and 238 controls to evaluate traditional and emerging risk factors for ischemic stroke including tHcy and ADMA plasma levels. RESULTS: The median plasma levels of tHcy were 8.48 MUM for controls and 10.01 MUM for cases (P<0.0001). Plasma levels of tHcy between 12 and 50MUM were considered moderate hyperhomocysteinemia (HtHcy). There were no differences in plasma ADMA concentration between groups (P=0.40). Plasma levels of ADMA and creatinine were not correlated (P=0.47). After adjusting for confounding factors, the presence of HtHcy was strongly associated with stroke (OR 8.97; P<0.0001). The adjusted association between HtHcy and stroke in men (OR 9.98) was comparable to that in women (OR 8.98) (P=0.41). CONCLUSIONS: In this Hispanic population, with relatively normal renal function, plasma levels of tHcy but not ADMA were associated with stroke independent of other cardiovascular risk factors. PMID- 21978130 TI - Partial ABCC8 gene deletion mutations causing diazoxide-unresponsive hyperinsulinaemic hypoglycaemia. AB - Inactivating mutations in the pancreatic beta cell ATP-sensitive potassium (K(ATP) ) channel genes are identified by sequencing in approximately 80% of patients with diazoxide-unresponsive hyperinsulinaemic hypoglycaemia (HH). Genetic testing is clinically important as the mode of inheritance of a K(ATP) channel mutation(s) provides information on the histological subtype. For example in patients with a single paternally inherited mutation a focal lesion is possible and once confirmed, the patient can undergo a curative lesionectomy. By contrast, recessive inheritance indicates diffuse disease, which requires near total pancreatectomy, if medical management is unsuccessful. We investigated ABCC8 and KCNJ11 gene dosage in 29 probands from a cohort of 125 with diazoxide unresponsive HH where sequencing did not provide a genetic diagnosis. We identified heterozygous partial ABCC8 deletions in four probands. In two cases with focal pancreatic disease, a paternally inherited deletion was found. Two other probands with diffuse pancreatic disease were compound heterozygotes for a deletion and a recessively acting mutation that had been identified by sequencing. Family member studies confirmed compound heterozygosity for the deletion and the missense mutation in two affected siblings of one proband. Heterozygous deletions of the ABCC8 gene are a rare, but important cause of diazoxide-unresponsive HH. Dosage analysis should be undertaken in all patients when sequencing analysis does not confirm the genetic diagnosis as confirmation of the mode of inheritance can guide clinical management and will provide important information regarding recurrence risk. PMID- 21978132 TI - Cholinesterase inhibition activity of Marsilea quadrifolia Linn. an edible leafy vegetable from West Bengal, India. AB - Maesilea quadrifolia Linn. (Marsileaceae) is a leafy vegetable well known in India. The current study aims to explore the phytochemical profile of M. quadrifolia and investigate its anti-cholinesterase potential. The methanol extract of the plant was subjected to qualitative and quantitative phytochemical screening (total alkaloidal content, saponin content and phenol content) and its anti-cholinesterase potential was tested by TLC bioautography and other screening methods using acytylcholinesterase (AChE) and butyrylcholinesterase (BChE). The study revealed that the extract contains various classes of phytoconstituents including steroids, saponins, alkaloids and other polyphenols. Total alkaloid, phenolic and saponin contents were found to be 19.3 mg g-1 and 158.5 +/- 1.02 mg g-1 as gallic acid equivalents and 2.63 mg g-1 of the extract, respectively. The TLC bioautography method exhibited the inhibition of both enzymes. In a microtiter plate assay, the IC50 values of the extract for AChE and BChE were found to be 51.89 +/- 0.24 ug mL-1 and 109.43 +/- 2.82 ug mL-1, respectively. These findings suggest that M. quadrifolia is a potential lead as an AChE and BChE inhibitor, which may be useful in the management of Alzheimer's disease. PMID- 21978134 TI - Metal-organic frameworks for separations. PMID- 21978133 TI - Mitochondrial dysfunction in retinal diseases. AB - The mitochondrion is a vital intracellular organelle for retinal cell function and survival. There is growing confirmation to support an association between mitochondrial dysfunction and a number of retinal degenerations. Investigations have also unveiled mitochondrial genomic instability as one of the contributing factors for age-related retinal pathophysiology. This review highlights the role of mitochondrial dysfunction originating from oxidative stress in the etiology of retinal diseases including diabetic retinopathy, glaucoma and age-related macular degeneration (AMD). Moreover, mitochondrial DNA (mtDNA) damage associated with AMD due to susceptibility of mtDNA to oxidative damage and failure of mtDNA repair pathways is also highlighted in this review. The susceptibility of neural retina and retinal pigment epithelium (RPE) mitochondria to oxidative damage with ageing appears to be a major factor in retinal degeneration. It thus appears that the mitochondrion is a weak link in the antioxidant defenses of retinal cells. In addition, failure of mtDNA repair pathways can also specifically contribute towards pathogenesis of AMD. This review will further summarize the prospective role of mitochondria targeting therapeutic agents for the treatment of retinal disease. Mitochondria based drug targeting to diminish oxidative stress or promote repair of mtDNA damage may offer potential alternatives for the treatment of various retinal degenerative diseases. PMID- 21978135 TI - Is autonomy related to the quality of performance of everyday activities in children with spina bifida? AB - PURPOSE: To investigate the relationship between the level of autonomy and the quality of performance of everyday activities in a population-based cohort of children with spina bifida and to study the agreement between the children's and the parents' ratings of autonomy. METHODS: 50 dyads of children (aged 6-14) with spina bifida and their parents rated the children's level of autonomy with an adapted, Swedish version of the Autonomy Scale from the Arc's Self-Determination Scale. Each child's quality of performance of everyday activities was assessed with the Assessment of Motor and Process Skills (AMPS). RESULTS: The autonomy levels of the children with spina bifida were rated to be lowest in daily routines and highest in leisure activities. Binary logistic regression analyses revealed that age, motor skills and process skills were all significantly related to the autonomy level, but that process skills appeared to predominate in this respect. Concerning the perception of the autonomy level, little agreement was found between each child and his/her parent. CONCLUSIONS: It is important to understand and support the development of process skills as expressed in task performance in children with spina bifida and to pay attention to both the parent's and the child's opinion when setting goals and plans for interventions. PMID- 21978136 TI - Incorporating effectiveness of community-based management in a national marine gap analysis for Fiji. AB - Every action in a conservation plan has a different level of effect and consequently contributes differentially to conservation. We examined how several community-based, marine, management actions differed in their contribution to national-level conservation goals in Fiji. We held a workshop with experts on local fauna and flora and local marine management actions to translate conservation goals developed by the national government into ecosystem-specific quantitative objectives and to estimate the relative effectiveness of Fiji's community-based management actions in achieving these objectives. The national conservation objectives were to effectively manage 30% of the nation's fringing reefs, nonfringing reefs, mangroves, and intertidal ecosystems (30% objective) and 10% of other benthic ecosystems (10% objective). The experts evaluated the contribution of the various management actions toward national objectives. Scores ranged from 0 (ineffective) to 1 (maximum effectiveness) and included the following management actions: permanent closures (i.e., all extractive use of resources prohibited indefinitely) (score of 1); conditional closures harvested once per year or less as dictated by a management plan (0.50-0.95); conditional closures harvested without predetermined frequency or duration (0.10-0.85); other management actions, such as regulations on gear and species harvested (0.15 0.50). Through 3 gap analyses, we assessed whether the conservation objectives in Fiji had been achieved. Each analysis was based on a different assumption: (1) all parts of locally managed marine areas (including closures and other management) conserve species and ecosystems effectively; (2) closures conserve species and ecosystems, whereas areas outside closures, open to varying levels of resource extraction, do not; and (3) actions that allow different levels of resource extraction vary in their ability to conserve species and ecosystems. Under assumption 1, Fiji's national conservation objectives were exceeded in all marine ecosystems; under assumption 2, none of Fiji's conservation objectives were met; and under assumption 3, on the basis of the scores assigned by experts, Fiji achieved the 10% but not the 30% objectives for ecosystems. Understanding the relative contribution of management actions to achieving conservation objectives is critical in the assessment of conservation achievements at the national level, where multiple management actions will be needed to achieve national conservation objectives. PMID- 21978137 TI - Nontarget analysis of urine by electrospray ionization-high field asymmetric waveform ion mobility-tandem mass spectrometry. AB - Nearly a decade after first commercialization, high field asymmetric waveform ion mobility spectrometry (FAIMS) has yet to find its place in routine chemical analysis. Prototypes have been used to demonstrate the utility of this separation technique combined with mass spectrometry (MS). Unfortunately, first generation commercial FAIMS instruments have gone practically unused by early adopters. Here, we show this to be due to poor ion transmission in the FAIMS-MS source interface. We present simple instrumental modifications and optimization of experimental conditions to achieve good performance from the first generation commercial FAIMS device (the Ionalytics Selectra) coupled to a high resolution Q TOF-MS. In combination with nanospray ionization, we demonstrate for the first time the nontarget analysis of urine by FAIMS with minimal sample preparation. We show the unique suitability of electrospray ionization (ESI)-FAIMS-MS for identification of low abundance species such as urinary biomarkers of damage of nucleic acids in a complex biological matrix. The elimination of electrospray noise and matrix components by FAIMS and the continuous flow of analytes through FAIMS for accurate and tandem mass analysis produce high quality spectral data suitable for structural identification of unknowns. These characteristics make ESI-FAIMS-MS ideal for nontarget identification, even when compared to high efficiency LC-ESI-MS. PMID- 21978138 TI - Electroanalytical determination of the sunscreen agent octocrylene in cosmetic products. AB - An electroanalytical method was developed to detect and quantify the sunscreen agent octocrylene (OCR) in cosmetic products. The method was based on electrochemical reduction, using voltammetric techniques. OCR was reduced at 0.97 V vs. Ag/AgCl on a glassy carbon electrode using a mixture of Britton Robinson buffer (0.04 mol L(-1)) and ethanol (7 : 3, v/v) as the supporting electrolyte solution. Under optimized conditions and square-wave voltammetry, OCR response was linear from 5.0 * 10(-6) to 8.0 * 10(-5) mol L(-1) (r = 0.9995), with a limit of detection of 2.8 * 10(-6) mol L(-1). The proposed electroanalytical method proved simple, fast and suitable for detection and quantification of OCR in samples of cosmetic products, with satisfactory results in the recovery test and analytical determination in real samples. PMID- 21978139 TI - Employers' readiness for the mother-friendly workplace: an elicitation study. AB - Currently over half of mothers of infants under 1-year-old are in the workforce in the United States. These women face challenges to continue breastfeeding when they return to work 3 to 6 months post-partum. This study explored the perspectives of employers on mother-friendly environments to assess their readiness to provide breastfeeding accommodation using the elicitation under the theory of planned behaviour. Researchers conducted phone/in-person interviews with a convenient sample of 20 human resource managers from companies that had 500 or more employees in the New York metropolitan area in 2009. Content analyses identified the common concepts that represent underlying beliefs of the constructs of the theory. The demography of the participants is 40% male and 80% White, with mean ages of 34.3+/-8.5 years. 'Happy employees' and 'high retention rate and improved loyalty' were the most frequently mentioned (95%) benefits to the company (behavioural beliefs). Supporters of a mother-friendly environment (normative beliefs) in the workplace included 'mothers and expectant mothers (70%)', and 'managers supervising women and new mothers (55%)'. Most frequently mentioned company drawbacks (control beliefs) were 'not cost effective (65%)' and 'time consuming (65%)', followed by 'perception of special favours for some (50%)'. Workplace breastfeeding promotion efforts can be successful by reinforcing positive beliefs and addressing the challenges associated with implementation of breastfeeding accommodation through education and other incentives such as recognition of model companies and tax breaks. The identified beliefs provide a basis for the development of a quantitative instrument to study workplace breastfeeding support further. PMID- 21978140 TI - Can vouchers make a difference to the use of private primary care services by older people? Experience from the healthcare reform programme in Hong Kong. AB - BACKGROUND: As part of its ongoing healthcare reform, the Hong Kong Government introduced a voucher scheme, intended for encouraging older patients to use primary healthcare services in the private sector, thereby, reducing burden on the overwhelmed public sector. The voucher program is also considered one of the strategies to further develop the public private partnership in healthcare, a policy direction of high political priority as indicated in the Chief Executive Policy Address in 2008-09. This study assessed whether the voucher scheme, as implemented so far, has reached its intended goals, and how it might be further improved in the context of public-private partnership. METHODS: This was a cross sectional study using structured questionnaires by face-to-face interviews with older people aged 70 or above in Hong Kong, the target group of the demand-side voucher program. RESULTS: 71.2% of 1,026 older people were aware of the new voucher scheme but only 35.0% had ever used it. The majority of the older people used the vouchers for acute curative services in the private sector (82.4%) and spent less on preventive services. Despite the provision of vouchers valued US$30 per year as an incentive to encourage the use of private primary care services, after 12-months of implementation, 66.2% of all respondents agreed with the statement that "the voucher scheme does not change their health seeking behaviours on seeing public or private healthcare professionals". The most common reasons for no change in their behaviours included "I am used to seeing doctors in the public system" and "The amount of the subsidy is too low". Those who usually used a mix of public and private doctors and those with better self reported health condition compared to last year were more likely to perceive a change in their own health seeking behaviours. CONCLUSIONS: Our study showed that despite a reasonably high awareness of the voucher scheme, its usage was low. The voucher alone was not enough to realize the government's policy of greater use of the private primary care services. Greater publicity and more variety of media promotion would increase awareness but the effectiveness of vouchers in changing older people's behaviour needs to be revisited. Designating vouchers for use of preventive services with evidence-based practice could be considered. In addition to the demand-side subsidies, improving transparency and comparability of private services against the public sector might be necessary. PMID- 21978141 TI - Involvement of cyclin-dependent kinase-5 in the kainic acid-mediated degeneration of glutamatergic synapses in the rat hippocampus. AB - Increased levels of glutamate causing excitotoxic damage accompany neurological disorders such as ischemia/stroke, epilepsy and some neurodegenerative diseases. Cyclin-dependent kinase-5 (Cdk5) is important for synaptic plasticity and is deregulated in neurodegenerative diseases. However, the mechanisms by which kainic acid (KA)-induced excitotoxic damage involves Cdk5 in neuronal injury are not fully understood. In this work, we have thus studied involvement of Cdk5 in the KA-mediated degeneration of glutamatergic synapses in the rat hippocampus. KA induced degeneration of mossy fiber synapses and decreased glutamate receptor (GluR)6/7 and post-synaptic density protein 95 (PSD95) levels in rat hippocampus in vivo after intraventricular injection of KA. KA also increased the cleavage of Cdk5 regulatory protein p35, and Cdk5 phosphorylation in the hippocampus at 12 h after treatment. Studies with hippocampal neurons in vitro showed a rapid decline in GluR6/7 and PSD95 levels after KA treatment with the breakdown of p35 protein and phosphorylation of Cdk5. These changes depended on an increase in calcium as shown by the chelators 1,2-bis(o-aminophenoxy)ethane-N,N,N ',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM) and glycol-bis (2-aminoethylether)-N,N,N ',N ' tetra-acetic acid. Inhibition of Cdk5 using roscovitine or employing dominant negative Cdk5 and Cdk5 silencing RNA constructs counteracted the decreases in GluR6/7 and PSD95 levels induced by KA in hippocampal neurons. The dominant negative Cdk5 was also able to decrease neuronal degeneration induced by KA in cultured neurons. The results show that Cdk5 is essentially involved in the KA mediated alterations in synaptic proteins and in cell degeneration in hippocampal neurons after an excitotoxic injury. Inhibition of pathways activated by Cdk5 may be beneficial for treatment of synaptic degeneration and excitotoxicity observed in various brain diseases. PMID- 21978142 TI - Editorial. Trans-disciplinary research is needed about breast cancer. PMID- 21978143 TI - Influence of diabetes mellitus type 2 and prolonged estrogen exposure on risk of breast cancer among women in Armenia. AB - Diabetes mellitus type 2 (DM2) and breast cancer (BrCa) are prevalent in Armenia. We investigated DM2, reproductive factors, and BrCa in a case control study of 302 women. Multiple logistic regression analyses revealed DM2 increased adjusted odds of BrCa by 5.53 (95% CI 1.34-22.81). Any birth was protective (adjusted OR=0.36, 95% CI 0.20-0.66). Each year delay in first pregnancy increased risk (adjusted OR=1.13, 95% CI 1.01-1.27) as did induced abortions (adjusted OR=2.86, 95% CI 1.02-8.04). Odds ratios were adjusted for age and body mass index (BMI), which confounded associations between DM2 and BrCa. We suggest our findings imply the need for further investigation in Armenian and in other populations with similar characteristics. PMID- 21978144 TI - Beliefs related to breast cancer and breast cancer screening among Lebanese Armenian women. AB - Our purpose of this article was to investigate women's beliefs about breast cancer, breast cancer screening, and intervention programs. We designed the study using a cross-sectional/descriptive correlation. The participants were drawn from a convenience sample (N=94). The instrument included Champion's Revised Health Belief Model Scale (CHBMS). Analysis was performed using SPSS (2005), 15.0. More than sixty-four percent (64.8%) of women surveyed were over 41. Results showed that 80.9% of women surveyed had heard of breast self-exams (BSEs), while 76.6% had heard of mammography. However, 53.2% never practiced breast self examinations, and 79.6% never underwent mammography. Mean belief scores follow: low susceptibility (14.32), barriers to BSE (15.24), barriers to mammography (14.85), high seriousness (23.42), benefits to breast self-examination (22.7), confidence (36.45), health motivation (27.27), and benefits to mammography (24.28). Significant relationships included the relationship between barriers to breast self-examination and whether women had heard about breast self examinations (p=.02); the relationship between susceptibility and whether women had heard of or underwent mammography (p=.027); the relationship between confidence and whether women had heard of mammography (p=.056); the relationship between confidence and perceived financial status (p=.05); and benefits of mammography (p=.05). Appropriate interventions are developed. PMID- 21978145 TI - Mothers and daughters: intertwining relationships and the lived experience of breast cancer. AB - No relationship is more profound than the positional mother- daughter dyad. Each shares a physical, emotional, and spiritual link not experienced by others. The intrusion of breast cancer alters this normative dyadic relationship. In this article we explore this change through a hermeneutic reflective narrative inquiry, incorporating Bakhtinian dialogism, of the behavioral science literature, popular press, and other resources, and use of the motet to uncover the lived experience of women in this dyadic relationship. PMID- 21978146 TI - Experiences of recall after mammography screening--a qualitative study. AB - Women participating in biannual mammography screening for 20 years have a cumulative risk of 20% of being recalled. We conducted a prospective qualitative interview study with eight nonsymptomatic women recalled after mammography screening. These women expressed mixed emotions over being recalled. Information about recall rates and breast cancer risk was seen as alarming, and cancer risk estimates were seen by some as high. The short time between recall and examination was reassuring, but it was also perceived as an indication of malignancy. Despite distress from examinations, most of the women continued to want medical examinations to detect cancer early. PMID- 21978147 TI - Disparities between prescribing of secondary prevention therapies for stroke and coronary artery disease in general practice. AB - BACKGROUND: Extensive evidence exists regarding the effectiveness of secondary prevention measures in patients with cardiovascular disease. AIM: We aimed to examine the management and risk perceptions of cardiovascular events in people with established cardiovascular disease. METHODS: We analyzed data on 1453 patients, >=55 year old, with a history of cardiovascular disease, from the Australian Hypertension and Absolute Risk Study. RESULTS: Compared with those 533 patients with stroke/transient ischemic attack, the 743 patients with coronary artery disease were twice as likely to have been prescribed secondary prevention therapies even after adjustment for potential confounding variables (adjusted relative risks 1.85; 95% confidence interval 1.56-2.19, 42% vs. 73% for use of the combination of blood pressure-lowering, lipid-lowering and antiplatelet therapies) and to have better control of lipid and blood pressure levels. General practitioners estimated that only 27% of patients with stroke/transient ischemic attack - 38% of those with coronary artery disease and 41% of those with both conditions - were at a high risk (>=15%) of a recurrent event. Patients similarly underestimated their risk of recurrent cardiovascular events, with only 8% of stroke/transient ischemic attack, 11% of coronary and 15% of combination disease patients rating themselves at 'high' or 'very-high' risk. CONCLUSIONS: This study reaffirms the large treatment gap in the uptake of secondary prevention for cardiovascular disease in primary care settings, being much greater for patients with cerebral compared with cardiac cardiovascular disease. This appears to be related to differential perceptions of cardiovascular risk across different vascular territories in both patients and doctors. PMID- 21978148 TI - Membrane protrusion coarsening and nanotubulation within giant unilamellar vesicles. AB - Hydrophobic side groups on a stimuli-responsive polymer, encapsulated within a single giant unilamellar vesicle, enable membrane attachment during compartment formation at elevated temperatures. We thermally modulated the vesicle through implementation of an IR laser via an optical fiber, enabling localized directed heating. Polymer-membrane interactions were monitored using confocal imaging techniques as subsequent membrane protrusions occurred and lipid nanotubes formed in response to the polymer hydrogel contraction. These nanotubes, bridging the vesicle membrane to the contracting hydrogel, were retained on the surface of the polymer compartment, where they were transformed into smaller vesicles in a process reminiscent of cellular endocytosis. This development of a synthetic vesicle system containing a stimuli-responsive polymer could lead to a new platform for studying inter/intramembrane transport through lipid nanotubes. PMID- 21978149 TI - Pain as a global public health priority. AB - BACKGROUND: Pain is an enormous problem globally. Estimates suggest that 20% of adults suffer from pain globally and 10% are newly diagnosed with chronic pain each year. Nevertheless, the problem of pain has primarily been regarded as a medical problem, and has been little addressed by the field of public health. DISCUSSION: Despite the ubiquity of pain, whether acute, chronic or intermittent, public health scholars and practitioners have not addressed this issue as a public health problem. The importance of viewing pain through a public health lens allows one to understand pain as a multifaceted, interdisciplinary problem for which many of the causes are the social determinants of health. Addressing pain as a global public health issue will also aid in priority setting and formulating public health policy to address this problem, which, like most other chronic non-communicable diseases, is growing both in absolute numbers and in its inequitable distribution across the globe. SUMMARY: The prevalence, incidence, and vast social and health consequences of global pain requires that the public health community give due attention to this issue. Doing so will mean that health care providers and public health professionals will have a more comprehensive understanding of pain and the appropriate public health and social policy responses to this problem. PMID- 21978150 TI - Applicability of the polysulphone horizontal calibration to differently inclined dosimeters. AB - Polysulphone (PS) dosimetry has been a widely used technique for more than 30 years to quantify the erythemally effective UV dose received by anatomic sites (personal exposure). The calibration of PS dosimeters is an important issue as their spectral response is different from the erythemal action spectrum. It is performed exposing a set of PS dosimeters on a horizontal plane and measuring the UV doses received by dosimeters using calibrated spectroradiometers or radiometers. In this study, data collected during PS field campaigns (from 2004 to 2006), using horizontal and differently inclined dosimeters, were analyzed to provide some considerations on the transfer of the horizontal calibration to differently inclined dosimeters, as anatomic sites usually are. The role of sky conditions, of the angle of incidence between the sun and the normal to the slope, and of the type of surrounding surface on the calibration were investigated. It was concluded that PS horizontal calibrations apply to differently inclined dosimeters for incidence angles up to approximately 70 degrees and for surfaces excluding ones with high albedo. Caution should be used in the application of horizontal calibrations for cases of high-incidence angle and/or high albedo surfaces. PMID- 21978152 TI - Heat-shock protein 70 is associated with the entry of Marek's disease virus into fibroblast. AB - Literature pertaining to the interactions between Marek's disease virus (MDV) entry-related glycoproteins and corresponding receptors is still limited. Results from a Western blot analysis of cellular proteins for virus receptors and co immunoprecipitation suggest that heat shock protein 70 (HSP70) is a potential cellular receptor for MDV glycoprotein gH. Plaque inhibition assays confirm the involvement of HSP70 in the early stages of MDV entry into chicken embryo fibroblasts (CEF). The present work supports that HSP70 is implicated in the MDV entry process by binding to gH, and enhances the understanding of multifunctional HSP70 and the MDV infection process. PMID- 21978153 TI - Analysis of antigen epitopes and molecular pathogenic characteristics of the 2009 H1N1 pandemic influenza A virus in China. AB - In order to further predict the epidemic trend and develop vaccines for 2009 H1N1 virus, we monitored its epitopes and molecular pathogenic characteristics during the epidemic process. We also analyzed the similarity of antigenic and genetic characteristics among the novel 2009 H1N1, representative seasonal H1N1 strains, and vaccine strains. 2009 H1N1 isolates had high similarity of hemagglutinin (HA) antigenic sites with H1N1 viruses isolated before 1940 and up to 80.0% similarity with 1918 H1N1. The elderly people born before 1940 have relatively low 2009 H1N1 infection rate, which might be responsible for their previous infection with either 1918 H1N1 virus or an early progeny. Compared to seasonal H1N1 vaccine strains from 1999 to 2010, the HA, neuraminidase (NA), and nucleoprotein (NP) proteins of the isolates had highly conserved CTL epitopes (60.5-65.8%, 69.6 82.6%, and 76.7%, respectively). The seriousness and mortality rate of 2009 H1N1 infections were similar to seasonal influenza, which may be related to the molecular characteristics of low toxicity of 2009 H1N1 and cross-T-cell immunity, due to vaccination or exposure to seasonal H1N1 virus. Some strains of 2009 H1N1 acquired mutations at antigenic and glycosylation sites. It is of particular interest that Haishu/SWL110/10 and Beijing/SE2649/09, isolated after November 2009, gained a new glycosylation site at the position 179 of HA protein, near the RBD. Thus, in the future, vaccination with glycosylated 2009 H1N1 virus may prevent the seasonal epidemic caused by strains with glycosylation site mutation near the receptor binding domain (RBD). PMID- 21978154 TI - Horizontal gene transfer in herpesviruses identified by using support vector machine. AB - Horizontal gene transfer (HGT) is the probable origin of new genes. Identification of HGT-introduced genes would be helpful to the understanding of the genome evolution and the function prediction of new genes. In this study, a method using support vector machine (SVM) was used to distinguish horizontally transferred genes and non-horizontally transferred genes of mammalian herpesviruses based on the atypical composition identification, with accuracy higher than 95% within a reasonable length of time by using just a common PC. This identified 302 putative horizontally transferred genes, 171 genes being identified for the first time. Although most putative transferred genes are of unknown function, many genes have been discovered or predicted to encode glycoproteins or membrane proteins. PMID- 21978155 TI - Molecular characterization and pathogenicity of swine influenza H9N2 subtype virus A/swine/HeBei/012/2008/(H9N2). AB - The H9N2 subtype influenza virus (IV) is a remarkable member of the influenza A viruses because it can infect not only chickens, ducks and pigs, but also humans. Pigs are susceptible to both human and avian influenza viruses and have been proposed to be intermediate hosts for the generation of pandemic influenza viruses through reassortment or adaptation to the mammalian host. To further understand the genetic characteristics and evolution, we investigated the source and molecular characteristics of the H9N2 subtype swine influenza virus (SIV), and observed its pathogenicity in BALB/c mice. The BALB/c mice were inoculated intranasally with 100 median mouse infectious dose of A/swine/HeBei/012/2008/(H9N2) viruses to observe the pathogenicity. The HA, NP, NA and M gene were cloned, sequenced and phylogenetically analyzed with related sequences available in GenBank. The infected mice presented with inactivity, weight loss and laboured respiration, while the pathological changes were characterized by diffuse alveolar damage in the lung. The nucleotide and deduced amino acid sequence of HA, NP, NA and M gene was similar with that of A/chicken/Hebei/4/2008(H9N2). The HA protein contained 6 glycosylation sites and the motif of HA cleavage site was PARSSR GLF, which is characteristic of low pathogenic IV. In the HA, NP, M and NA gene phylogenetic trees, the isolate clustered with A/chicken/Hebei/4/2008(H9N2). The isolate possibly came from A/chicken/Hebei/4/2008(H9N2) and was partially varied during its cross-species spread. PMID- 21978156 TI - Immunogenicity of a truncated enterovirus 71 VP1 protein fused to a Newcastle disease virus nucleocapsid protein fragment in mice. AB - Enterovirus 71 (EV71) is one of the viruses that cause hand, foot and mouth disease. Its viral capsid protein 1 (VP1), which contains many neutralization epitopes, is an ideal target for vaccine development. Recently, we reported the induction of a strong immune response in rabbits to a truncated VP1 fragment (Nt VP1t) displayed on a recombinant Newcastle disease virus (NDV) capsid protein. Protective efficacy of this vaccine, however, can only be tested in mice, since all EV71 animal models thus far were developed in mouse systems. In this study, we evaluated the type of immune responses against the protein developed by adult BALB/c mice. Nt-VP1t protein induced high levels of VP1 IgG antibody production in mice. Purified VP1 antigen stimulated activation, proliferation and differentiation of splenocytes harvested from these mice. They also produced significant levels of IFN-gamma, a Th1-related cytokine. Taken together, Nt-VP1t protein is a potent immunogen in adult mice and our findings provide the data needed for testing of its protective efficacy in mouse models of EV71 infections. PMID- 21978157 TI - Studies on interaction of cucurbit aphid-borne yellow virus proteins using yeast two-hybrid system and bimolecular fluorescence complementation. AB - In this article, yeast two-hybrid system (YTHS) and bimolecular fluorescence complementation (BiFC) were used to analyze the interactions of cucurbit aphid borne yellows virus (CABYV)-encoded proteins. P0, P1, P1-2, P3, P4, and P5 were tested by YTHS in all possible pairwise combinations, and only P3/P3 interaction was detected. Results obtained by BiFC further confirmed the self-interaction of P3, and the subcellular localization of reconstituted YFP fluorescence was observed mainly in nuclei of Nicotiana benthamiana leaf epidermal cells. Domains involved in P3/P3 self-interaction were analyzed by YTHS and BiFC using deletion mutants. The results showed that R domain (residues 1-61) in the N-terminus could self-interact, and it also interacted with the S domain (residues 62-199) in the C-terminus of P3. The present work would serve as a molecular basis for further characterization of CABYV proteins, and the regions involved in P3/P3 self interaction could provide the clue for understanding the capsid assembly pathway of CABYV. PMID- 21978158 TI - Blockade of Lyn kinase upregulates both canonical and non-canonical TLR-3 pathways in THP-1 monocytes exposed to human cytomegalovirus. AB - Regulation of monocyte response to human cytomegalovirus (HCMV) occurs via activation of receptors that elicit innate antiviral effects and later T-cell responses. Our previous data (Yew et al.., 2010) demonstrated that human monocyte scavenger receptor A type 1 (SR-A1) are required for sensing of HCMV by endosomal toll-like receptors (TLRs)-3 and -9, which in turn induce critical pro inflammatory cytokines. However, it remains unclear which subcellular molecules associated with SR-A1 lead to downstream activation of TLR-3 and/or TLR-9 signaling pathways. Herein we report that Lyn kinase, associated physically and functionally with SR-A for low density lipoprotein (LDL) recognition, acts as a key SR-A1-induced kinase that plays a critical role in TLR-3/9 signal transduction upon HCMV exposure to THP-1 monocytes. We found that disruption of the SR-A1 signal transduction through molecular inhibition by Lyn kinase oligonucleotides not only blocks the activation of downstream TLR-9 pathway but also alters the downstream TLR-3 pathway. In particular, Lyn kinase oligonucleotides resulted in decreased expression of TLR-9-induced tumor necrosis factor alpha (TNF-alpha) but strongly upregulated canonical TLR-3-induced interferon beta (IFN-beta) and non-canonical TLR-3-induced NF-kappaB-dependent p35 (35kDa) subunit of interleukin 12 (IL-12p35) gene transcription. Thus, the observed shift away from TNF-alpha to robust IFN-beta and IL-12p35 induction may offer opportunities for therapeutic interventions. PMID- 21978159 TI - Antiviral properties of polysaccharides from Agaricus brasiliensis in the replication of bovine herpesvirus 1. AB - Natural products are an inexhaustible source of compounds with promising pharmacological activities, including antiviral action. In the present study, the antiviral potential of polysaccharide-peptide (PLS) and an extracted beta-glucan from Agaricus brasiliensis were investigated in the replication of bovine herpesvirus 1 (BoHV-1) in HEp-2 cell cultures. The cytotoxicity (CC50) was assayed by the MTT method and the antiviral activity (IC50) was estimated by the plaque reduction assay. To study the possible mode of action of PLS and beta glucan, the following protocols were performed: the virucidal assay, adsorption assay and the time-of-addition assay. The PLS presented a selectivity index (SI) higher than 12.50 and beta-glucan 9.19. The antiviral inhibition (67.9%) in cells treated with PLS during virus infection was higher than that in cells treated prior to or post infection. The beta-glucan presented high inhibition of virus replication by plaque assay (83.2%) and by immunofluorescence assay (63.8%). Although the mechanism has yet to be defined, we suggest that PLS and beta-glucan inhibited BoHV-1 replication by interfering with the early events of viral penetration. Additional studies are required for a better understanding of the mechanism of action of PLS and beta-glucan. PMID- 21978160 TI - Evaluation of anti-influenza efficiency of polyclonal IgG antibodies specific to the ectodomain of M2 protein of influenza A virus by passive immunization of mice. AB - We attempted to quantify the protective potential of polyclonal IgG antibodies specific to the ectodomain of M2 protein (eM2) of influenza A virus (IAV) against lethal influenza infection of mice. For this purpose, eM2 conjugated with keyhole limpet hemocyanin (KLH) or KLH alone were administered with Freund's adjuvant intraperitoneally (i.p.) to BALB/c mice. IgG antibodies specific to the KLH-eM2 conjugate (anti-KLH-eM2 IgGs) and KLH (anti-KLH IgGs), respectively, were purified from ascitic fluids. Analysis of the preparation of anti-KLH-eM2 IgGs by ELISA revealed that it contained about 25% of anti-eM2 IgGs and 75% of anti-KLH IgGs. Taking into account this finding mice were passively immunized by intravenous route with 320, 160, 80, and 40 ug of anti-eM2 IgGs per mouse, respectively, while 320 ug of anti-KLH IgGs were used in control. Following subsequent infection with 3 LD50 IAV the survival of mice was determined. An absolute protection (100% survival) was obtained with 320 ug of anti-eM2 IgGs, and a relatively strong significant protection (~80% survival, p = 0.024) with 160 ug. The amount 160 ug of IgGs represents approx. 100 ug IgGs per 1 ml of blood. PMID- 21978161 TI - Prevalence of porcine circovirus 2 infection in pig population in Slovakia. AB - The prevalence of porcine circovirus 2 (PCV-2) infection in the pig population in Slovakia was investigated. Sera from pigs suspected for post-weaning multisystemic wasting syndrome (PMWS) as well as clinically healthy pigs were tested for viral DNA and specific IgM and IgG antibodies. Pigs (n = 198) were categorized to weaning, grower and fattening ones and sows. The results showed that PCV-2 antibodies were present in 53.4% of PMWS-suspects, in 50.0% of healthy pigs and in 69.0% of sows. In PMWS-suspect grower pigs, 40.7% were positive for IgM+IgG antibodies and 22.2% for viral DNA. In PMWS-suspect fattening pigs, 50.0% were positive for IgM+IgG antibodies and 25.0% for viral DNA. In healthy fattening pigs, almost 90.0% were positive for IgG antibodies and 38.5% for viral DNA. The highest proportion of PMWS-suspects was in grower pigs and specific antibodies were increasing with the age of pigs. A combination of positivities for IgG+IgM antibodies and viral DNA was a highly significant marker of PMWS. Viral DNA was detected in seropositive as well as seronegative PMWS-suspects. Overall, in all categories of pigs tested, specific antibodies and viral DNA were detected in 54.0% and 35.5%, respectively. PMID- 21978162 TI - Evidence of conserved epitopes in variable region of VP8* subunit of VP4 protein of rotaviruses of P[8]-1 and P[8]-3 lineages. AB - Although antibody responses to the human rotavirus VP4 protein have been reported, few studies have analyzed the specificity of these responses to the VP8* subunit. This study investigated antibody responses generated against the variable region of the VP4 protein (VP8* subunit) in children infected with rotavirus genotype P[8]. Recombinant VP8* subunit (rVP8*) and truncations corresponding aa 1-102
(peptide A) and 84-180 (peptide B) of rotavirus strains P[8]-1 and P[8]-3 lineages were expressed in Escherichia coli and examined for antibody reactivity using ELISA and Western blot assays. Sera from infected children had IgG antibodies that reacted with full-length rVP8*, peptide A and B of both lineages, with stronger reactivity observed against peptide B. In addition, anti-strain Wa (P[8]-1) and anti-rVP8* (P[8]-3) rabbit polyclonal antiserum reacted against peptide B sequences of both lineages. These data indicate that the VP8* variable region of rotavirus belonging to P[8]-1 and P[8] 3 lineages have conserved epitopes recognized by antibodies elicited during natural infections. PMID- 21978164 TI - Nucleocapsid protein gene mediated resistance against groundnut bud necrosis virus in tomato using sense and antisense constructs. PMID- 21978163 TI - Small interfering RNAs targeting viral structural envelope protein genes and the 5'-UTR inhibit replication of bovine viral diarrhea virus in MDBK cells. AB - Bovine viral diarrhea viruses (BVDVs) are important pathogens of cattle that occur worldwide, and for which no antiviral therapy is available. In the present study, the inhibitory effect of small interfering (si) RNAs on bovine viral diarrhea virus 1 (BVDV-1) replication in cultured bovine cells was explored. Four synthetic siRNAs were designed to target structural envelope region genes (Erns, E1, and E2) and one cocktail of siRNA was generated to target the 5'-UTR of the BVDV-1 genome. The inhibitory effects of siRNAs were assessed by determination of infectious viral titer, viral antigen and viral RNA. The siRNA cocktail and three of the synthetic siRNAs produced moderate anti-BVDV-1 effect in vitro as shown by 25%-40% reduction in BVDV-1 antigen production, 7.9-19.9-fold reduction in viral titer and 21-48-fold reduction in BVDV-1 RNA copy number. Our findings suggest that siRNA cocktail targeted at the 5'-UTR is a stronger inhibitor of BVDV-1 replication and the targets for siRNA inhibition can be extended to BVDV-1 structural envelope protein genes. PMID- 21978165 TI - Development of real-time RT-PCR for human metapneumovirus. PMID- 21978166 TI - Content analysis of newspaper coverage of the Florida panther. AB - Populations of large carnivores are declining globally, and analysis of public discourse about carnivores is useful for understanding public opinion and influences on management and policy. Portrayal of carnivores in the media affects public perceptions and support for their conservation. We conducted a content analysis of 513 articles about Florida panthers (Puma concolor coryi) published from 2003 to 2006 in newspapers with local circulation in core panther habitat in southwest Florida and papers with statewide circulation to compare the differences in the amount of coverage and portrayals of panther risks to people and property on the basis of proximity of human communities to panthers. Local papers published significantly more news articles and significantly longer news articles primarily about panthers. Articles in local and statewide papers used both episodic frames, which focus on specific occurrences (e.g., a panther sighting or predation) and thematic frames, which focus on general trends (e.g., abundance of panthers over time). Local articles more often emphasized risks that panthers might harm people, pets, or livestock than statewide papers. Our results are consistent with theory that proximity to human-carnivore conflict influences perceptions and salience of risks posed by large carnivores. Most articles mentioned panthers as a secondary topic, which we believe was a result of the relevance an endangered carnivore has in discussions of public land management, development, and regulations in Florida. Claims made by sources quoted in each article had a neutral to positive depiction of panthers, and most quotations were from federal and state agency scientists. We suggest continued use by the media of agency sources provides the opportunity for clear, concordant messages about panther management. Content analysis provides a way to monitor media portrayal of carnivores for consistency with agency outreach goals. PMID- 21978167 TI - The glucokinase mutation p.T206P is common among MODY patients of Jewish Ashkenazi descent. AB - BACKGROUND: Maturity-onset diabetes of the young (MODY) is characterized by an autosomal dominant mode of inheritance; a primary defect in insulin secretion with non-ketotic hyperglycemia, age of onset under 25 yr; and lack of autoantibodies. Heterozygous mutations in glucokinase (GCK) are associated with mild fasting hyperglycemia and gestational diabetes mellitus while homozygous or compound heterozygous GCK mutations result in permanent neonatal diabetes mellitus. Given that both the Israeli-Arabic and the various Israeli-Jewish communities tend to maintain ethnic seclusion, we speculated that it would be possible to identify a relatively narrow spectrum of mutations in the Israeli population. OBJECTIVE: To characterize the genetic basis of GCK-MODY in the different ethnic groups of the Israeli population. SUBJECTS: Patients with clinically identified GCK-MODY and their first degree family members. METHODS: Molecular analysis of GCK was performed on genomic DNA using polymerase chain reaction, denaturing gradient gel electrophoresis (DGGE), and sequencing. Bioinformatic model was preformed using the NEST program. RESULTS: Mutations in GCK were identified in 25 families and were all family-specific, except c.616A>C. p.T206P. This mutation was identified in six unrelated families, all patients from a Jewish-Ashkenazi descent, thus indicating an ethno-genetic correlation. A simple, fast, and relatively cheap DGGE/restriction-digestion assay was developed. CONCLUSIONS: The high incidence of the mutant allele in GCK-MODY patients of Jewish-Ashkenazi descent suggests a founder effect. We propose that clinically identified GCK-MODY patients of Jewish-Ashkenazi origin be first tested for this mutation. PMID- 21978169 TI - Soluble VEGFR1 (sVEGFR1) as a novel marker of amyotrophic lateral sclerosis (ALS) in the North Indian ALS patients. AB - BACKGROUND AND PURPOSE: North Indian patients with amyotrophic lateral sclerosis (ALS) exhibit substantially extended survival time after onset of the disease as compared to their Western counterparts. Earlier, we found that vascular endothelial growth factor-A (VEGF-A) may be associated with increased survival of these patients. We now measured soluble vascular endothelial growth factor receptor-1 (sVEGFR1), an inhibitor receptor for VEGF-A, in these patients with ALS. METHODS: Patients with sporadic ALS (n = 36) attending the Neurology Outpatient at Post Graduate Institute of Medical Education and Research (PGIMER) at Chandigarh were included on the basis of El Escorial criteria. The sVEGFR1 levels were analyzed in serum of these patients using enzyme-linked immunosorbent assay (ELISA) and compared with normal controls (n = 36). RESULTS: Soluble vascular endothelial growth factor receptor-1 was found to be decreased significantly in serum of patients with ALS. Serum obtained from definite ALS revealed significantly lower sVEGFR1 as compared to probable ALS. However, there was no difference in serum sVEGFR1 levels between male and female patients with ALS. CONCLUSIONS: Soluble vascular endothelial growth factor receptor-1 downregulation may result in increased serum VEGF-A reported previously in our patients with ALS and may indicate the activation of compensatory mechanism in response to neurodegeneration. The lower serum sVEGFR1 levels may have a possible clinicopathological association, if not causal, to the extended survival of North Indian patients with ALS; however, the result needs further investigations particularly in comparable Caucasian ALS population. PMID- 21978170 TI - Branched alpha-(1,4) glucans from Lentinula edodes (L10) in combination with radiation enhance cytotoxic effect on human lung adenocarcinoma through the Toll like receptor 4 mediated induction of THP-1 differentiation/activation. AB - This work investigated the role of structure in the binding of polysaccharides from 10 regionally different strains of Lentinula edodes to Toll-like receptor 4 (TLR-4) on monocytes (THP-1) and the potential effect of this interaction on tumor cell viability. Principal component analysis and multiple linear regression identified arabinose, glucose 1 -> 4 linkage, and molecular weights about 2700 and 534 kDa as the significant determinant factors associated with TLR-4 binding activity. The branched alpha-(1,4)-glucan (L10) had the strongest ability to bind to TLR-4 and induce THP-1 cell differentiation. L10 induction of the THP-1 cell differentiation, superoxide production, and cytokine production followed the TLR 4/MyD88/IKK/NFkappaB pathway. Coculture of irradiated human lung adenocarcinoma A549 cells with L10-activated THP-1 cells resulted in significantly decreased percentage of viable A549 cells from 66 to 37% (p = 0.018), increased levels of superoxide, interleukin-8, and RANTES, and decreased levels of angiogenin and vascular endothelial growth factor. The results indicate that L10-activated monocytes have the potential to boost the antitumor immune response and antitumor activity of radiotherapy. PMID- 21978171 TI - A chemical investigation of the Antarctic sponge Lyssodendoryx flabellata. AB - From the Antarctic sponge Lyssodendoryx flabellata, a new polycyclic compound, which we named flabellone, related to the oestrogenic hormone oestrone, has been elucidated by spectrometric and spectroscopic means. Along with flabellone, a glycosphingolipid (GSL) mixture featuring an unusual alpha-fucofuranosyl-3-beta glucopyranoside unit structurally identical to the previously reported terpioside has been isolated and identified. The mixture of GSL homologues exhibited inhibitory effects in mixed lymphocyte reactions on human cells. PMID- 21978172 TI - Populations of carbonic acid isomers at 210 K from a fast two-electron reduced density matrix theory. AB - Parametrization of the 2-electron reduced density matrix (2-RDM) rather than the many-electron wave function yields a new family of electronic-structure methods that are faster and more accurate than traditional coupled electron-pair methods including coupled cluster with single and double excitations. Deriving the parametrization from N-representability conditions generates a 2-RDM that captures significant correlation from triple and higher-order excitations at the cost of double excitations. We apply the parametric 2-RDM method to confirm recent experiments determining the relative thermodynamic populations of the cis cis and cis-trans isomers of carbonic acid. In 2010 Bernard et al. showed by infrared spectroscopy that the populations of cis-cis and cis-trans isomers have a 10:1 ratio at 210 K. By use of the parametric 2-RDM method, we predict a 8:1 ratio at 210 K. Comparable ab initio methods overestimate the stability of the cis-cis isomer with 24:1 and 21:1 ratios. These 2-RDM-based methods promise to have significant applications throughout chemistry. PMID- 21978173 TI - The illusion and the paradox of being autonomous, experiences from persons with spinal cord injury in their transition period from hospital to home. AB - PURPOSE: To open a discourse on the concept of autonomy as a precursor for participation in individuals with Spinal Cord Injury (SCI) by exploring the experiences about their perceived autonomy in their transition period from hospital to home. METHOD: Based on the 'grounded theory' approach; in-depth, semi structured interviews were conducted with 11 SCI-patients. A theoretical sampling strategy was used and the data was analysed according to the constant comparative method. RESULTS: To capture this complexity of autonomy, the results have been structured in themes with regard to the self of the patient and his independency. The analysis showed four different typologies of how autonomy is perceived; (1) the active agent, (2) the active follower, (3) the passive follower and (4) the passive victim. CONCLUSION: Rehabilitation professionals can help individuals in disconnecting their internalised ideal of independency to avoid the illusion of being autonomous and can gain insight in the patients' typology and empower patients to avoid the paradox of being autonomous. If the ultimate goal of rehabilitation is participation; empowering the patient to achieve a 'sense of agency' instead of autonomy is the central goal for rehabilitation professionals. Empowerment and agency are key topics for the patient to gain mastery over his own life. PMID- 21978174 TI - Direct detection of point mutations in nonamplified human genomic DNA. AB - Ultrasensitive detection protocols not requiring polymerase chain reaction (PCR) mediated target DNA amplification are expected to significantly improve our possibilities in several research and diagnostic applications for which minute cell quantities are available. For this reason we have tested a nanoparticle enhanced surface plasmon resonance imaging (SPRI) sensing strategy to detect point mutations in nonamplified genomic DNA. We have used genomic DNAs, not subject to costly, time-consuming, and prone to contamination PCR-based amplification procedures, obtained from both healthy individuals and homozygous or heterozygous patients affected by beta-thalassemia, in order to demonstrate the specificity and the sensitivity of the described sensing strategy. The assay we describe is ultrasensitive and convenient. Attomolar concentrations of target genomic DNA are detected, DNAs from healthy individuals and homozygous or heterozygous patients affected by beta-thalassemia are discriminated, and only simple manipulations of the genetic samples are required before the analysis. The proposed ultrasensitive detection of DNA point mutations involved in genomic disorders possibly represents an important advantage in several biomedical applications. PMID- 21978176 TI - Health-related quality of life in subjects with and without Type 2 diabetes: pooled analysis of five population-based surveys in Germany. AB - AIMS: To estimate population values of health-related quality of life (HRQL) in subjects with and without Type 2 diabetes mellitus across several large population-based survey studies in Germany. Systematic differences in relation to age and sex were of particular interest. METHODS: Individual data from four population-based studies from different regions throughout Germany and the nationwide German National Health Interview and Examination Survey (GNHIES98) were included in a pooled analysis of primary data (N = 9579). HRQL was assessed using the generic index instrument SF-36 (36-item Short Form Health Survey) or its shorter version, the SF-12 (12 items). Regression analysis was carried out to examine the association between Type 2 diabetes and the two component scores derived from the SF-36/SF-12, the physical component summary score (PCS-12) and the mental component summary score (MCS-12), as well as interaction effects with age and sex. RESULTS: The PCS-12 differed significantly by -4.1 points in subjects with Type 2 diabetes in comparison with subjects without Type 2 diabetes. Type 2 diabetes was associated with significantly lower MCS-12 in women only. Higher age was associated with lower PCS-12, but with an increase in MCS 12, for subjects with and without Type 2 diabetes. CONCLUSIONS: Pooled analysis of population-based primary data offers HRQL values for subjects with Type 2 diabetes in Germany, stratified by age and sex. Type 2 diabetes has negative consequences for HRQL, particularly for women. This underlines the burden of disease and the importance of diabetes prevention. Factors that disadvantage women with Type 2 diabetes need to be researched more thoroughly. PMID- 21978175 TI - Large scale mitochondrial sequencing in Mexican Americans suggests a reappraisal of Native American origins. AB - BACKGROUND: The Asian origin of Native Americans is largely accepted. However uncertainties persist regarding the source population(s) within Asia, the divergence and arrival time(s) of the founder groups, the number of expansion events, and migration routes into the New World. mtDNA data, presented over the past two decades, have been used to suggest a single-migration model for which the Beringian land mass plays an important role. RESULTS: In our analysis of 568 mitochondrial genomes, the coalescent age estimates of shared roots between Native American and Siberian-Asian lineages, calculated using two different mutation rates, are A4 (27.5 +/- 6.8 kya/22.7 +/- 7.4 kya), C1 (21.4 +/- 2.7 kya/16.4 +/- 1.5 kya), C4 (21.0 +/- 4.6 kya/20.0 +/- 6.4 kya), and D4e1 (24.1 +/- 9.0 kya/17.9 +/- 10.0 kya). The coalescent age estimates of pan-American haplogroups calculated using the same two mutation rates (A2:19.5 +/- 1.3 kya/16.1 +/- 1.5 kya, B2:20.8 +/- 2.0 kya/18.1 +/- 2.4 kya, C1:21.4 +/- 2.7 kya/16.4 +/- 1.5 kya and D1:17.2 +/- 2.0 kya/14.9 +/- 2.2 kya) and estimates of population expansions within America (~21-16 kya), support the pre-Clovis occupation of the New World. The phylogeography of sublineages within American haplogroups A2, B2, D1 and the C1b, C1c and C1d subhaplogroups of C1 are complex and largely specific to geographical North, Central and South America. However some sub-branches (B2b, C1b, C1c, C1d and D1f) already existed in American founder haplogroups before expansion into the America. CONCLUSIONS: Our results suggest that Native American founders diverged from their Siberian-Asian progenitors sometime during the last glacial maximum (LGM) and expanded into America soon after the LGM peak (~20-16 kya). The phylogeography of haplogroup C1 suggest that this American founder haplogroup differentiated in Siberia-Asia. The situation is less clear for haplogroup B2, however haplogroups A2 and D1 may have differentiated soon after the Native American founders divergence. A moderate population bottle neck in American founder populations just before the expansion most plausibly resulted in few founder types in America. The similar estimates of the diversity indices and Bayesian skyline analysis in North America, Central America and South America suggest almost simultaneous (~ 2.0 ky from South to North America) colonization of these geographical regions with rapid population expansion differentiating into more or less regional branches across the pan American haplogroups. PMID- 21978177 TI - Assistive technology and prediction of happiness in people withpost-polio syndrome. AB - PURPOSE: To explore the relationship between level of happiness in people with post-polio syndrome (PPS) and assistive technology (AT) by taking into account confounding factors such as age, gender and house composition. METHOD: Existing data from 218 adults with PPS, who had completed a cross-sectional survey conducted by the British Polio Fellowship in 2007, were used for a secondary quantitative analysis. Ordinal logistic regression was applied to determine whether ownership of or the need for AT predicted happiness in people with PPS. RESULTS: Ownership of AT did not predict happiness, whereas the perceived need for AT was a significant predictor of feeling less happy (p = 0.028). Among the different types of AT needed, only need of home adaptations combined with major equipment was close to being significantly associated with less happiness (p = 0.078). Being older (p < 0.001) and living with a partner (p < 0.001) significantly increased the likelihood of feeling happier. CONCLUSION: The findings indicate the importance of the contribution of need for AT in explaining happiness in people with PPS. The fact that users reported unmet equipment needs urge for increased user decision making and better understanding of why perceived needs are not resolved. [Box: see text]. PMID- 21978178 TI - Acceleration of conjugated dienyne cycloaromatization. PMID- 21978179 TI - Intravitreal bevacizumab for macular edema due to central retinal vein occlusion: perfused vs. ischemic and early vs. late treatment. AB - PURPOSE/AIMS: This study investigates the efficacy of intravitreal bevacizumab (IVB) for cystoid macular edema (CME) secondary to central retinal vein occlusion (CRVO). Subgroup analysis was performed comparing early (within 90 days of CRVO onset) and late treatment (after 90 days) as well as perfused and ischemic subgroups. MATERIALS AND METHODS: Retrospective review of 48 consecutive eyes with CRVO treated with IVB was performed. Data collected at various time points included best corrected visual acuity (BCVA), central foveal thickness (FT) on optical coherence tomography (OCT), perfusion status on fluorescein angiography (FA), and complications. RESULTS: Mean initial BCVA was 20/288 compared to 20/214 at 12 months (p=0.07) and 20/204 (p=0.03) at final follow-up. Initial mean central FT was 591 micrometers compared to 339 micrometers at 12 months (p=0.003). Mean follow-up was 10.5 months, and mean number of injections was 3.7. After IVB, no significant difference in BCVA gain or edema resolution on OCT was noted between the early and late treatment groups or between the perfused and ischemic subgroups. CONCLUSIONS: IVB improves foveal thickness in eyes with CRVO, but this does not always correlate with visual recovery. No difference in efficacy was observed for IVB treatment of perfused versus ischemic CRVO or when used for early versus late treatment. PMID- 21978180 TI - Age, gender, insulin and blood glucose control status alter the risk of ischemic heart disease and stroke among elderly diabetic patients. AB - BACKGROUND: We analyzed the effects of insulin therapy, age and gender on the risk of ischemic heart disease (IHD) and cerebrovascular accident (CVA) according to glycemic control. METHODS AND RESULTS: We performed a prospective cohort study (Japan Cholesterol and Diabetes Mellitus Study) of type 2 diabetes patients (n = 4014) for 2 years. The primary endpoint was the onset of fatal/non-fatal IHD and/or CVA, which occurred at rates of 7.9 and 7.2 per 1000 person-years, respectively. We divided diabetic patients into four groups based on age (<= 70 and > 70) and hemoglobin A1C levels (<= 7.0 and > 7.0%). Multiple regression analysis revealed that IHD was associated with high systolic blood pressure and low HDL-C in patients under 70 years of age with fair glycemic control and was associated with low diastolic blood pressure in the older/fair group. Interestingly, insulin use was associated with IHD in the older/poor group (OR = 2.27, 95% CI = 1.11-5.89; p = 0.026) and was associated with CVA in the older/fair group (OR = 2.09, 95% CI = 1.06-4.25; p = 0.028). CVA was associated with lower HDL-C and longer duration of diabetes in younger/poor glycemic control group. Results by stepwise analysis were similar. Next, patients were divided into four groups based on gender and diabetic control(hemoglobinA1C < or > 7.0%). Multiple regression analysis revealed that IHD was associated with high systolic blood pressure in male/fair glycemic control group, age in male/poor control group, and short duration of diabetic history in females in both glycemic control groups. Interestingly, insulin use was associated with IHD in the male/poor group(OR = 4.11, 95% CI = 1.22-8.12; p = 0.018) and with CVA in the female/poor group(OR = 3.26, 95% CI = 1.12-6.24; p = 0.02). CVA was associated with short duration of diabetes in both female groups. CONCLUSIONS: IHD and CVA risks are affected by specific factors in diabetics, such as treatment, gender and age. Specifically, insulin use has a potential role in preventing IHD but may also be a risk factor for CVA among the diabetic elderly, thus revealing a need to develop improved treatment strategies for diabetes in elderly patients. The Japan Cholesterol and Diabetes Mellitus Study was formulated to evaluate them(Umin Clinical Trials Registry, clinical trial reg. no. UMIN00000516; http://www.umin.ac.jp/ctr/index.htm). PMID- 21978181 TI - Social determinants of iron supplementation among women of reproductive age: a systematic review of qualitative data. AB - Iron supplementation for women of reproductive age is a main part of an interdisciplinary strategy recommended for the control and prevention of iron deficiency and the treatment of mild-to-moderate iron-deficiency anaemia. This systematic review reports the findings from a meta-synthesis of qualitative data concerning the experiences and perceptions of iron supplementation among women of reproductive age and health service providers worldwide. Qualitative systematic review methods were used to conduct a search of published literature, define inclusion and exclusion criteria, appraise quality of studies and extract data on the use of iron supplementation among women of reproductive age. Coding, thematic analysis, reciprocal translation and line of argument synthesis were used to synthesize data. Twelve studies spanning 17 countries met inclusion criteria and were included in the analysis. Seven domains emerged from the review: cultural norms and societal values including explanatory models and medical pluralism; political and socio-economic circumstances; education and communication; social organization and social relationships; health care access and supplement supply; food and nutrition availability; and adherence. In addition, 16 sub-domains are highlighted. Connecting review findings to a conceptual framework of social determinants of health highlights salient issues that policy makers must consider when adapting global iron supplementation recommendations to the local context. PMID- 21978182 TI - Raman signature of graphene superlattices. AB - When two identical two-dimensional periodic structures are superposed, a mismatch rotation angle between the structures generates a superlattice. This effect is commonly observed in graphite, where the rotation between graphene layers generates Moire patterns in scanning tunneling microscopy images. Here, a study of intravalley and intervalley double-resonance Raman processes mediated by static potentials in rotationally stacked bilayer graphene is presented. The peak properties depend on the mismatch rotation angle and can be used as an optical signature for superlattices in bilayer graphene. An atomic force microscopy system is used to produce and identify specific rotationally stacked bilayer graphenes that demonstrate the validity of our model. PMID- 21978183 TI - Analysis of changes in the association of income and the utilization of curative health services in Mexico between 2000 and 2006. AB - BACKGROUND: A common characteristic of health systems in most developing countries is unequal access to health services. As a result, members of the poorest population groups often do not receive formal attention for health services, because they cannot afford it. In 2001 in Mexico, to address income related differences in the use of health services, the government launched a major healthcare reform, which includes a health insurance program called Seguro Popular, aimed at improving healthcare access among poor, uninsured residents. This paper analyzes the before and after changes in the demand for curative ambulatory health services focusing on the association of income-related characteristics and the utilization of formal healthcare providers vs. no healthcare service utilization. METHODS: By using two nationally representative health surveys (ENSA-2000 and ENSANUT-2006), we modeled an individual's decision when experiencing an illness to use services provided by the (1) Ministry of Health (MoH), (2) social security, (3) private entities, or (4) to not use formal services (no healthcare service utilization). RESULTS: Poorer individuals were more likely in 2006 than in 2000 to respond to an illness by using formal healthcare providers. Trends in provider selection differed, however. The probability of using public services from the MoH increased among the poorest population, while the findings indicated an increase in utilization of private health services among members of low- and middle-income groups. No significant change was seen among formal workers -covered by social security services-, regardless of socioeconomic status. CONCLUSIONS: Overall, for 2006 the Mexican population appears less differentiated in using healthcare across economic groups than in 2000. This may be related, in part, to the implementation of Seguro Popular, which seems to be stimulating healthcare demand among the poorest and previously uninsured segment of the population. Still, public health authorities need to address the remaining income-related healthcare utilization differences, the differences in quality between public and private health services, and the general perception that MoH facilities offer inferior services. PMID- 21978184 TI - Palladium-catalyzed Hiyama cross-coupling of aryltrifluorosilanes with aryl and heteroaryl chlorides. AB - An efficient, palladium-catalyzed Hiyama cross-coupling reaction of aryltrifluorosilanes with aryl chlorides has been developed. A wide variety of functionalized biaryl derivatives were isolated in good to excellent yields. The scope of this reaction has also been extended to heteroaryl chlorides, affording the corresponding heterobiaryl compounds in high yields. PMID- 21978186 TI - The transforming growth factor-beta receptor genes and the risk of intracranial aneurysms. AB - BACKGROUND: Mutations in the receptor genes of the transforming growth factor beta pathway, TGFBR1 and TGFBR2, cause syndromes with thoracic aortic aneurysms, while genetic variants in TGFBR1 and TGFBR2 are associated with abdominal aortic aneurysms. The transforming growth factor-beta pathway may be involved in aneurysm development in general. Aims To analyze whether genetics variants in TGFBR1 and TGFBR2 are also involved in the pathogenesis of intracranial aneurysms. METHODS: Using tag single nucleotide polymorphisms, we analyzed all common genetic variants in TGFBR1 (five single nucleotide polymorphisms) and TGFBR2 (26 single nucleotide polymorphisms) in a Dutch intracranial aneurysm case control population approach using a two-stage genotyping approach. RESULTS: In stage 1, on analyzing 481 patients and 648 controls, two of the five single nucleotide polymorphisms in TGFBR1 were associated with intracranial aneurysm with P < 0.10. In an independent cohort of 310 intracranial aneurysm patients and 376 controls, a predominance of the allele of the two single nucleotide polymorphisms found more frequently in patients in stage 1 was also observed in patients of stage 2 but the associations were not statistically significant. On combined analyses of both stages, there was a statistically significant association of both single nucleotide polymorphisms with intracranial aneurysm (single nucleotide polymorphism rs1626340, odds ratio 1.24, 95% confidence intervals 1.05-1.46, P = 0.01; single nucleotide polymorphism rs10819634, odds ratio 1.23, 95% confidence intervals 1.03-1.46, P = 0.02) but these associations did not hold after multiple testing correction (i.e., P < 0.0016, 0.05/31). Also, no differences in the single nucleotide polymorphism frequency were observed for TGFBR2 between patients and controls. CONCLUSIONS: We found no evidence for TGFBR1 and TGFBR2 as susceptibility genes for intracranial aneurysm in the Dutch population. PMID- 21978185 TI - Use of cone beam computed tomography in the diagnosis, planning and follow up of a type III dens invaginatus case. AB - AIM: To present the case of a maxillary left lateral incisor with Oehlers' type III dens invaginatus in which cone beam computed tomography (CBCT) was used as an adjunctive resource in the diagnosis as well as in the planning and 2-year follow up of the nonsurgical/surgical treatment. SUMMARY: The tooth had two root canals: a primary (main) canal with vital pulp that appeared to be closed apically and an invaginated canal that was necrotic, wide-open at the portal of exit and associated with a large chronic periapical lesion extending to the apex of the maxillary left central incisor. Radiographic tracking of a sinus tract in the labial gingiva of the affected tooth with a gutta-percha point revealed its origin to be the invagination. The CBCT scans revealed that the periapical radiolucency was significantly larger than seen radiographically as well as an increased thickness of the buccal cortical plate. Conventional root canal treatment of the primary canal was undertaken. As nonsurgical access to the invaginated canal was not possible, endodontic surgery was performed for curettage of the lesion, root-end cavity preparation using ultrasonic tips and root canal filling with white mineral trioxide aggregate (MTA). CBCT scanning after 17 months and clinical and radiographic follow-up after 24 months revealed complete periapical repair and absence of symptoms. KEY LEARNING POINTS: The combination of nonsurgical and surgical treatments produced periapical repair in a tooth with type III dens invaginatus with two root canals. CBCT may aid the diagnosis as well as the management plan and follow-up of teeth with this developmental anomaly. PMID- 21978187 TI - Primary pleural epithelioid mesothelioma of clear cell type: a case report and review of current literature. AB - Primary pleural epithelioid mesothelioma with clear cell morphology is a particularly rare neoplasm, with only a few documented cases. Here, the authors report a case of a 76-year-old man, with a history of asbestos exposure, admitted for mild dyspnea. Radiologic examination revealed right pleural effusion and pleural thickening. Cytological examination of aspirated pleural samples was consistent with non-small cell carcinoma. Histological examination of the resected, via VATS, plural specimens was consistent with the diagnosis of clear cell epithelioid mesothelioma. The authors further analyze the main morphological and immunohistochemical features of clear cell epithelioid mesothelioma, emphasizing the algorithm for excluding other clear cell tumors metastatic to the pleura. PMID- 21978188 TI - Scanning noise microscopy on graphene devices. AB - We developed a scanning noise microscopy (SNM) method and demonstrated the nanoscale noise analysis of a graphene strip-based device. Here, a Pt tip made a direct contact on the surface of a nanodevice to measure the current noise spectrum through it. Then, the measured noise spectrum was analyzed by an empirical model to extract the noise characteristics only from the device channel. As a proof of concept, we demonstrated the scaling behavior analysis of the noise in graphene strips. Furthermore, we performed the nanoscale noise mapping on a graphene channel, allowing us to study the effect of structural defects on the noise of the graphene channel. The SNM method is a powerful tool for nanoscale noise analysis and should play a significant role in basic research on nanoscale devices. PMID- 21978189 TI - Vestibular modulation of somatosensory perception. AB - Functional imaging studies show that vestibular and somatosensory projections overlap in the human brain. However, it remains unclear whether and how vestibular inputs affect somatosensory function. To address this issue, we studied the effects of left caloric vestibular stimulation (CVS) on detection of near-threshold somatosensory stimuli delivered to the left and right hands of healthy volunteers. To investigate whether these effects were somatosensory specific, or supramodal, we also tested CVS modulation of visual contrast detection. Signal detection analyses showed increased somatosensory perceptual sensitivity immediately after CVS, both ipsilaterally and contralaterally. No statistically reliable effects on visual contrast sensitivity were found. These findings suggest that vestibular stimulation has a specific facilitatory effect on somatosensory detection, distinct from non-specific arousal and spatial attentional effects of CVS. Thus, the overlap in brain activations for vestibular and somatosensory inputs is not simply an anatomical curiosity, but may reflect a functional cross-modal perceptual interaction. PMID- 21978190 TI - Probing the interaction between prostacyclin synthase and prostaglandin H2 analogues or inhibitors via a combination of resonance Raman spectroscopy and molecular dynamics simulation approaches. AB - In an aim to probe the structure-function relationship of prostacyclin synthase (PGIS), resonance Raman (RR) spectroscopy and molecular dynamic (MD) simulation approaches have been exploited to characterize the heme conformation and heme protein matrix interactions for human PGIS (hPGIS) and zebrafish PGIS (zPGIS) in the presence and absence of ligands. The high-frequency RR (1300-1700 cm(-1)) indicates that the heme group is in the ferric, six-coordinate, low-spin state for both resting and ligand-bound hPGIS/zPGIS. The low-frequency RR (300-500 cm( 1)) and MD simulation reveal a salient difference in propionate-protein matrix interactions between hPGIS and zPGIS, as evident by a predominant propionate bending vibration at 386 cm(-1) in resting hPGIS, but two vibrations near 370 and 387 cm(-1) in resting zPGIS. Upon binding of a substrate analogue (U46619, U51605, or U44069), both hPGIS and zPGIS induce a distinctive perturbation of the propionate-protein matrix interactions, resulting in similar Raman shifts to ~381 cm(-1). On the contrary, the bending vibration remains unchanged upon binding of inhibitor/ligand (minoxidil, clotrimazole, or miconazole), indicating that these inhibitors/ligands do not interfere with the propionate-protein matrix interactions. These results, together with subtle changes in vinyl bending modes, demonstrate drastically different RR shifts with heme conformational changes in both hPGIS and zPGIS upon different ligand bindings, suggesting that PGIS exhibits a ligand-specific heme conformational change to accommodate the substrate binding. This substrate-induced modulation of the heme conformation may confer high product fidelity upon PGIS catalysis. PMID- 21978191 TI - Effect of nanoconfinement on kinetics of cross-linking reactions: a molecular simulation study. AB - We have used molecular dynamics simulations to study the effect of nanoconfinement on the kinetics of cross-linking reactions. Specifically, a bead spring model is used to carry out reactive molecular dynamics simulations of the autocatalytic epoxy curing reactions. In this simple model, if two colliding molecules arrive in spatial proximity, they react to form a new bond with a specified probability. The kinetics of the reaction in the bulk was compared with that in a cylindrical pore. Our simulations show that confinement leads to an increase in both the translational mobility of the beads as well as the average displacement undergone by the beads from their initial position to the position of reaction. The net result of these opposing factors is that the rate of curing reaction in the confinement is quantitatively similar to that in the bulk. We also observed heterogeneity of reaction rates in the confined system. As compared to the reaction rate in the bulk, the reaction rate in the first layer near the pore wall is lower, whereas the reaction rate in the central core domain of the nanopore hardly shows any difference from the bulk value except in the high conversion stage. The results suggest that the reaction rate in the confined system relative to the bulk will vary with the relative volume fractions of the first layer near the wall and the central core domain. PMID- 21978192 TI - Manual acupuncture for relieving pain associated with panretinal photocoagulation. AB - OBJECTIVE: The feasibility of manual acupuncture for reducing pain associated with panretinal photocoagulation (PRP) was investigated. METHODS: This was a prospective, comparative nonrandomized study on patients with proliferative diabetic retinopathy who were receiving PRP treatment. The protocol of PRP included three sequential sessions of treatment at 2-week intervals. Both the acupuncture (acuPRP) and control groups had no acupuncture in the first session. In the second session, acupuncture was given to the acuPRP group only. The third session of PRP completed the laser treatment course. Acupuncture performed only at GB 37 (Guangming) just before PRP, and the needle was removed after the treatment. An 11-point Likert-type verbal pain score test was given to all patients after each PRP treatment. RESULTS: Of 34 patients with proliferative diabetic retinopathy, 18 patients were allocated to the acuPRP group and 16 patients were allocated to the control group. After the first PRP treatment, there was no statistical difference in mean pain scores between the acuPRP and control groups (6.8+/-1.2 versus 6.3+/-2.1, respectively, p=0.383). After the second PRP treatment, the mean pain score in the acuPRP group was significantly lower, compared with the control group (3.9+/-1.8 versus 7.4+/-1.9, respectively, p<0.0001). Within the group, the mean pain scores were significantly higher during the second PRP treatment, compared with the first PRP treatment, in the control group (p=0.0003). In contrast, the mean pain scores were significantly lower during the second PRP treatment, compared with the first PRP treatment in the acuPRP group (p<0.0001). No adverse reactions or complications were noted. CONCLUSIONS: Acupuncture might help reduce pain during PRP treatment. However, further randomized studies are necessary to verify these preliminary results. PMID- 21978193 TI - Evaluation of a modified QuEChERS extraction of multiple classes of pesticides from a rice paddy soil by LC-APCI-MS/MS. AB - A new method for the determination of clomazone, fipronil, tebuconazole, propiconazole, and azoxystrobin in samples of rice paddy soil is presented. The extraction of the pesticides from soil samples was performed by using a modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) method. Some extraction conditions such as salt addition, sample acidification, use of buffer, and cleanup step were evaluated. The optimized method dealt with a single extraction of the compounds under study with acidified acetonitrile, followed by the addition of MgSO(4) and NaCl prior to the final determination by liquid chromatography-atmospheric chemical pressure ionization-tandem mass spectrometry. Validation studies were carried out in soil samples. Recoveries of the spiked samples ranged between 70.3 and 120% with relative standard deviation lower than 18.2%. The limits of quantification were between 10 and 50 MUg kg(-1). The method was applied to the analysis of real samples of soils where rice is cultivated. PMID- 21978194 TI - Individual-scale variation, species-scale differences: inference needed to understand diversity. AB - As ecological data are usually analysed at a scale different from the one at which the process of interest operates, interpretations can be confusing and controversial. For example, hypothesised differences between species do not operate at the species level, but concern individuals responding to environmental variation, including competition with neighbours. Aggregated data from many individuals subject to spatio-temporal variation are used to produce species level averages, which marginalise away the relevant (process-level) scale. Paradoxically, the higher the dimensionality, the more ways there are to differ, yet the more species appear the same. The aggregate becomes increasingly irrelevant and misleading. Standard analyses can make species look the same, reverse species rankings along niche axes, make the surprising prediction that a species decreases in abundance when a competitor is removed from a model, or simply preclude parameter estimation. Aggregation explains why niche differences hidden at the species level become apparent upon disaggregation to the individual level, why models suggest that individual-level variation has a minor impact on diversity when disaggregation shows it to be important, and why literature-based synthesis can be unfruitful. We show how to identify when aggregation is the problem, where it has caused controversy, and propose three ways to address it. PMID- 21978195 TI - Antioxidant, xanthine oxidase and lipoxygenase inhibitory activities and phenolics of Bauhinia rufescens Lam. (Caesalpiniaceae). AB - An aqueous acetone extract of the stem with the leaves of Bauhinia rufescens and its fractions were analysed for their antioxidant and enzyme-inhibitory activities, as well as their phytochemical composition. For measurement of the antioxidant activities, the 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azinobis(3 ethylbenzoline-6-sulphonate) and the ferric-reducing methods were used. The results indicated that the aqueous acetone, its ethyl acetate and n-butanol fractions possessed considerable antioxidant activity. Further, the xanthine oxidase and lipoxygenase inhibitory assays showed that the n-butanol fraction possessed compounds that can inhibit both these enzymes. In the phytochemical analysis, the ethyl acetate and the n-butanol fractions of the aqueous acetone extract were screened by HPLC-MS for their phenolic content. The results indicated the presence of hyperoside, isoquercitrin, rutin quercetin, quercitrin, p-coumaric and ferulic acids in the non-hydrolysed fractions. In the hydrolysed fractions, kaempferol, p-coumaric and ferulic acids were identified. PMID- 21978196 TI - Heterotopic Purkinje cells in ataxia-telangiectasia. AB - Ataxia-telangiectasia (A-T) is a heritable disorder of cerebellar ataxia and oculocutaneous telangiectasias caused by mutation of the ATM gene. The most prominent and consistent neuropathologic finding in the disorder is cerebellar cortical degeneration involving significant loss of granule and Purkinje cells. Several past autopsy studies of A-T patients have also noted large-bodied cells located within the molecular layer of the cerebellar cortex and, noting similarities in morphology between these cells and Purkinje cells, hypothesized that the cells were heterotopic Purkinje cells. This study aimed to test this hypothesis using an antibody that labels Purkinje cells, and also to investigate other cell types in the degenerating cerebellar cortex in A-T. Using the anti calbindin D-28K antibody to label Purkinje cells in cerebellar tissue from five A T patients and five age- and sex-matched controls, the study found calbindin positive heterotopic Purkinje cells in the molecular layer occurring at a significantly higher rate in A-T patients than in controls (P = 0.012). Further immunohistochemistry with the anti-Iba-1 and anti-parvalbumin antibodies showed, respectively, an increase in microglial activity (P = 0.14) and stellate-cell density (P = 0.0048) in the cerebellar cortex of A-T patients versus controls. These data add to the as yet unresolved debate over the origin and significance of heterotopic Purkinje cells in A-T. PMID- 21978202 TI - Development of the International Classification of Functioning, Disability and Health core sets for hand conditions--results of the World Health Organization International Consensus process. AB - PURPOSE: A formal decision-making and consensus process was applied to develop the first version of the International Classification on Functioning, Disability and Health (ICF) Core Sets for Hand Conditions. METHOD: To convene an international panel to develop the ICF Core Sets for Hand Conditions (HC), preparatory studies were conducted, which included an expert survey, a systematic literature review, a qualitative study and an empirical data collection process involving persons with hand conditions. A consensus conference was convened in Switzerland in May 2009 that was attended by 23 healthcare professionals, who treat hand conditions, representing 22 countries. RESULTS: The preparatory studies identified a set of 743 ICF categories at the second, third or fourth hierarchical level. Altogether, 117 chapter-, second-, or third-level categories were included in the comprehensive ICF Core Set for HC. The brief ICF Core Set for HC included a total of 23 chapter- and second-level categories. CONCLUSIONS: A formal consensus process integrating evidence and expert opinion based on the ICF led to the formal adoption of the ICF Core Sets for Hand Conditions. The next phase of this ICF project is to conduct a formal validation process to establish its applicability in clinical settings. PMID- 21978203 TI - Poor numeracy skills are associated with glycaemic control in Type 1 diabetes. AB - AIMS: To assess the numeracy and literacy skills of individuals with Type 1 diabetes and determine if there is a relationship with achieved glycaemic control independent of their duration of diabetes, diabetes education, demographic and socio-economic factors. METHODS: One hundred and twelve patients completed the study (mean current age 43.8 +/- 12.5 years, 47% male, mean duration of diabetes 22.0 +/- 13.2 years) out of 650 randomly selected patients from the Bournemouth Diabetes and Endocrine Centre's diabetes register. The Skills for Life Initial Assessments were used to measure numeracy and literacy. These indicate skills levels up to level 2, equivalent to the national General Certificate of Secondary Education grades A*-C. HbA(1c) was also measured. Pearson's correlation was used to measure the correlation of numeracy and literacy scores with HbA(1c.) To compare mean HbA(1c) between those with or without level 2 skills, t-tests were used, and multiple linear regression was used to investigate whether any differences were independent of duration of diabetes, diabetes education, demographic and socio-economic factors. RESULTS: Literacy was not associated with achieved HbA(1c). In contrast, participants with numeracy skills at level 2 or above achieved an HbA(1c) lower than those with numeracy skills below level 2 (P = 0.027). Although higher socio-economic status was associated with lower mean HbA(1c) , the relationship between numeracy and HbA(1c) appeared to be independent of socio-economic factors. CONCLUSIONS: Low numeracy skills were adversely associated with diabetes control. Assessment of numeracy skills may be relevant to the structure of diabetes education programmes. PMID- 21978204 TI - Fully analytical integration over the 3D volume bounded by the beta sphere in topological atoms. AB - Atomic properties of a topological atom are obtained by 3D integration over the volume of its atomic basin. Algorithms that compute atomic properties typically integrate over two subspaces: the volume bounded by the so-called beta sphere, which is centered at the nucleus and completely contained within the atomic basin, and the volume of the remaining part of the basin. Here we show how the usual quadrature over the beta sphere volume can be replaced by a fully analytical 3D integration leading to the atomic charge (monopole moment) for s, p, and d functions. Spherical tensor multipole moments have also been implemented and tested up to hexadecupole for s functions only, and up to quadrupole for s and p functions. The new algorithm is illustrated by operating on capped glycine (HF/6-31G, 35 molecular orbitals (MOs), 322 Gaussian primitives, 19 nuclei), the protein crambin (HF/3-21G, 1260 MOs, 5922 primitives and 642 nuclei), and tin (Z = 50) in Sn(2)(CH(3))(2) (B3LYP/cc-pVTZ and LANL2DZ, 59 MOs, 1352 primitives). PMID- 21978205 TI - Continuous IOP fluctuation recording in normal tension glaucoma patients. AB - BACKGROUND: Intraocular pressure (IOP) remains the only treatable risk factor of progressive glaucoma. Recently a device became available to continuously record IOP fluctuation in contrast to classical, discreet IOP measurements. OBJECTIVES: To perform 24-h IOP fluctuation monitoring using a CE-marked silicone lens embedded strain gauge sensor (SENSIMED Triggerfish) in five normal tension glaucoma patients in the presence and absence of anti-glaucomatous treatment and to show the clinical importance of this diagnostic tool. METHODS: 24-h continuous IOP fluctuation monitoring was performed on two occasions separated by at least 6 weeks in each patient. In the control session patients were untreated or previous IOP-lowering medication was washed-out for at least 6 weeks. In the treatment session patients received IOP-lowering medication for at least 6 weeks. The continuous recordings were analyzed for differences between daytime and nighttime data and for repeatability over time. Furthermore, profiles recorded in each patient in treated and non-treated conditions were compared. RESULTS: Highly individual and repeatable profiles were obtained. Data recorded during daytime portions of the recordings showed higher coefficients of variation than nighttime data. Positive and significant linear slopes for the transition period from wake time to sleep time were detected in all patients in the absence of anti glaucomatous treatment, while in three patients of five no significant slopes were detected under treated conditions. CONCLUSION: Our data suggest that the continuous IOP fluctuation monitoring device is sensitive to individual IOP rhythms and to differences in such rhythms due to anti-glaucomatous drug therapy. PMID- 21978206 TI - Strongly enhanced molecular fluorescence inside a nanoscale waveguide gap. AB - We experimentally demonstrate dramatically enhanced light-matter interaction for molecules placed inside the nanometer scale gap of a plasmonic waveguide. We observe spontaneous emission rate enhancements of up to about 60 times due to strong optical localization in two dimensions. This rate enhancement is a nonresonant nature of the plasmonic waveguide under study overcoming the fundamental bandwidth limitation of conventional devices. Moreover, we show that about 85% of molecular emission couples into the waveguide highlighting the dominance of the nanoscale optical mode in competing with quenching processes. Such optics at molecular length scales paves the way toward integrated on-chip photon source, rapid transfer of quantum information, and efficient light extraction for solid-state-lighting devices. PMID- 21978207 TI - Array CGH phylogeny: how accurate are comparative genomic hybridization-based trees? AB - BACKGROUND: Array-based Comparative Genomic Hybridization (CGH) data have been used to infer phylogenetic relationships. However, the reliability of array CGH analysis to determine evolutionary relationships has not been well established. In most CGH work, all species and strains are compared to a single reference species, whose genome was used to design the array. In the accompanying work, we critically evaluated CGH-based phylogeny using simulated competitive hybridization data. This work showed that a limited number of conditions, principally the tree topology and placement of the reference taxon in the tree, had a strong effect on the ability to recover the correct tree topology. Here, we add to our simulation study by testing the use of CGH as a phylogenetic tool with experimental CGH data from competitive hybridizations between N. crassa and other Neurospora species. In the discussion, we add to our empirical study of Neurospora by reanalyzing of data from a previous CGH phylogenetic analysis of the yeast sensu stricto complex. RESULTS: Array ratio data for Neurospora and related species were normalized with loess, robust spline, and linear ratio based methods, and then used to construct Neighbor-Joining and parsimony trees. These trees were compared to published phylogenetic analyses for Neurospora based on multilocus sequence analysis (MLSA). For the Neurospora dataset, the best combination of methods resulted in recovery of the MLSA tree topology less than half the time. Our reanalysis of a yeast dataset found that trees identical to established phylogeny were recovered only by pruning taxa - including the reference taxon - from the analysis. CONCLUSION: Our results indicate that CGH data can be problematic for phylogenetic analysis. Success fluctuates based on the methods utilized to construct the tree and the taxa included. Selective pruning of the taxa improves the results - an impractical approach for normal phylogenetic analysis. From the more successful methods we make suggestions on the normalization and post-normalization methods that work best in estimating genetic distance between taxa. PMID- 21978208 TI - Breastfeeding duration, age of starting solids and high BMI risk and adiposity in Indian children. AB - This study utilized data from a prospective birth cohort study on 568 Indian children, to determine whether a longer duration of breastfeeding and later introduction of solid feeding were associated with a reduced higher body mass index (BMI) and less adiposity. Main outcomes were high BMI (>90th within-cohort sex-specific BMI percentile) and sum of skinfold thickness (triceps and subscapular) at age 5. Main exposures were breastfeeding (six categories from 1-4 to >=21 months) and age of starting regular solid feeding (four categories from <=3 to >=6 months). Data on infant-feeding practices, socio-economic and maternal factors were collected by questionnaire. Birthweight, maternal and child anthropometry were measured. Multiple regression analysis that accounted for potential confounders demonstrated a small magnitude of effect for breastfeeding duration or introduction of solid feeds on the risk of high BMI but not for lower skinfold thickness. Breastfeeding duration was strongly negatively associated with weight gain (0-2 years) [adjusted beta = -0.12 standard deviation, 95% confidence interval (CI): -0.19 to -0.05 per category change in breastfeeding duration, P = 0.001], and weight gain (0-2 years) was strongly associated with high BMI at 5 years (adjusted odds ratio = 3.8, 95% CI: 2.53-5.56, P < 0.001). In our sample, findings suggest that longer breastfeeding duration and later introduction of solids has a small reduction on later high BMI risk and a negligible effect on skinfold thickness. However, accounting for sampling variability, these findings cannot exclude the possibility of no effect at the population level. PMID- 21978209 TI - Heterologous expression, biochemical characterization, and overproduction of alkaline alpha-amylase from Bacillus alcalophilus in Bacillus subtilis. AB - BACKGROUND: Alkaline alpha-amylases have potential applications for hydrolyzing starch under high pH conditions in the starch and textile industries and as ingredients in detergents for automatic dishwashers and laundries. While the alkaline alpha-amylase gains increased industrial interest, the yield of alkaline alpha-amylases from wild-type microbes is low, and the combination of genetic engineering and process optimization is necessary to achieve the overproduction of alkaline alpha-amylase. RESULTS: The alkaline alpha-amylase gene from Bacillus alcalophilus JN21 (CCTCC NO. M 2011229) was cloned and expressed in Bacillus subtilis strain WB600 with vector pMA5. The recombinant alkaline alpha-amylase was stable at pH from 7.0 to 11.0 and temperature below 40 degrees C. The optimum pH and temperature of alkaline alpha-amylase was 9.0 and 50 degrees C, respectively. Using soluble starch as the substrate, the Km and Vmax of alkaline alpha-amylase were 9.64 g/L and 0.80 g/(L.min), respectively. The effects of medium compositions (starch, peptone, and soybean meal) and temperature on the recombinant production of alkaline alpha-amylase in B. subtilis were investigated. Under the optimal conditions (starch concentration 0.6% (w/v), peptone concentration 1.45% (w/v), soybean meal concentration 1.3% (w/v), and temperature 37 degrees C), the highest yield of alkaline alpha-amylase reached 415 U/mL. The yield of alkaline alpha-amylase in a 3-L fermentor reached 441 U/mL, which was 79 times that of native alkaline alpha-amylase from B. alcalophilus JN21. CONCLUSIONS: This is the first report concerning the heterologous expression of alkaline alpha-amylase in B. subtilis, and the obtained results make it feasible to achieve the industrial production of alkaline alpha-amylase with the recombinant B. subtilis. PMID- 21978210 TI - Very early poststroke aphasia therapy: a pilot randomized controlled efficacy trial. AB - BACKGROUND AND PURPOSE: Early stroke rehabilitation has shown benefits over spontaneous recovery. Insufficient evidence exists to determine the benefits of early aphasia intervention. We hypothesized that daily aphasia therapy would show better communication outcomes than usual care (UC) in early poststroke recovery. METHOD: This prospective, randomized, single-blinded, controlled trial was conducted in three acute-care hospitals in Perth, Australia, each with over 200 stroke admissions annually. Patients with acute stroke causing moderate to severe aphasia were recruited at a median of three-days (range: 0-10 days) to receive daily aphasia therapy or usual care therapy. Individually tailored, impairment based intervention was provided for the acute hospital stay or intervention phase (median: 19 days; range: 5-76). Primary outcome measures were the aphasia quotient and functional communication profile at acute hospital discharge or four weeks poststroke, whichever came first. A random-number generator and sealed envelopes were used to randomize participants. Assessments were completed by a blinded assessor. RESULTS: Fifty-nine participants were recruited, with six withdrawals (10%) and seven deaths (12%) at six-months. Ninety percent had ischemic strokes, with 56.5% experiencing a total anterior circulation stroke. The group mean (+/- SD) age was 69.1 (+/- 13.9) years. Six participants (18.75%) in the daily aphasia therapy group did not complete the minimum (150 min) therapy required for this study. The daily aphasia therapy intervention phase mean therapy session time was 45 min (range: 30-80) and the total mean amount of therapy for the daily aphasia therapy participants was 331 min (range: 30-1415). Four (15%) participants in the usual care group received therapy. The collective total therapy provided to these participants was 295 min over seven sessions. Usual care participants received an average of 10.5 min of therapy per week during the intervention phase. At the primary end point, a generalized estimating equations model demonstrated that after controlling for initial aphasia severity, participants receiving daily aphasia therapy scored 15.1 more points (P = 0.010) on the aphasia quotient and 11.3 more points (P = 0.004) on the functional communication profile than those receiving usual care therapy. CONCLUSIONS: Daily aphasia therapy in very early stroke recovery improved communication outcomes in people with moderate to severe aphasia. PMID- 21978212 TI - The visuomotor mental rotation task: visuomotor transformation times are reduced for small and perceptually familiar angles. AB - In the visuomotor mental rotation (VMR) task, participants point to a location that deviates from a visual cue by a predetermined angle. This task elicits longer reaction times (RT) relative to tasks wherein the visual cue is spatially compatible with the movement goal. The authors previously reported that visuomotor transformations are faster and more efficient when VMR responses elicit a degree of dimensional overlap (i.e., 0 degrees and 5 degrees ) or when the transformation involves a perceptually familiar angle (i.e., 90 degrees or 180 degrees ; K. A. Neely & M. Heath, 2010b). One caveat to this finding is that standard and VMR responses were completed in separate blocks of trials. Thus, between-task differences not only reflect the temporal demands of the visuomotor transformations, but also reflect the temporal cost of response inhibition. The goal of this study was to isolate the time cost of visuomotor transformations in the VMR task. The results demonstrated that visuomotor transformations are more efficient and effective when the response entails a degree of dimensional overlap between target and response (i.e., when the angular disparity between the responses is small) or when the transformation angle is perceptually familiar. PMID- 21978211 TI - Intra-articular injections of sodium hyaluronate (Hyalgan(r)) in osteoarthritis of the knee. a randomized, controlled, double-blind, multicenter trial in the Asian population. AB - BACKGROUND: The efficacy and tolerability of 500-730 kDa sodium hyaluronate (Hyalgan(r)) for treatment of osteoarthritis (OA) pain has been established in clinical trials, but few data are available in the Asian population. We conducted a randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy and tolerability of this preparation in a Taiwanese population. METHODS: Two hundred patients with mild to moderate OA of the knee were randomized to receive five weekly intra-articular injections of sodium hyaluronate or placebo. The primary efficacy outcome was the change from baseline to Week 25 in patients' evaluation of pain using a 100-mm visual analog scale (VAS) during the 50-foot walking test. Additional outcomes included Western Ontario and McMaster Universities (WOMAC) scores, time on the 50-foot walking test, patient's and investigator's subjective assessment of effectiveness, acetaminophen consumption, and the amounts of synovial fluid. RESULTS: The Hyalgan(r) treatment group showed a significantly greater improvement from baseline to Week 25 in VAS pain on the 50-foot walking test than the placebo group (p = 0.0020). The Hyalgan(r) group revealed significant improvements from baseline to week 25 in WOMAC pain and function score than the placebo group (p = 0.005 and 0.0038, respectively) Other outcomes, such as time on the 50-foot walking test and subjective assessment of effectiveness, did not show any significant difference between groups. Both groups were safe and well tolerated. CONCLUSIONS: The present study suggests that five weekly intra-articular injections of sodium hyaluronate are well tolerated, can provide sustained relief of pain, and can improve function in Asian patients with osteoarthritis of the knee. TRIAL REGISTRATION: Therapeutic study, Level I 1a (randomized controlled trial with a significant difference). PMID- 21978213 TI - Dr. Jan Wojcicki to serve as co-editor of Eastern Europe. PMID- 21978215 TI - Social defeat stress induces hyperthermia through activation of thermoregulatory sympathetic premotor neurons in the medullary raphe region. AB - Psychological stress-induced hyperthermia is a fundamental autonomic response in mammals. However, the central circuitry underlying this stress response is poorly understood. Here, we sought to identify sympathetic premotor neurons that mediate a hyperthermic response to social defeat stress, a psychological stress model. Intruder rats that were defeated by a dominant resident conspecific exhibited a rapid increase in abdominal temperature by up to 2.0 degrees C. In these defeated rats, we found that expression of Fos, a marker of neuronal activation, was increased in the rostral medullary raphe region centered in the rostral raphe pallidus and adjacent raphe magnus nuclei. In this region, Fos expression was observed in a large population of neurons expressing vesicular glutamate transporter 3 (VGLUT3), which are known as sympathetic premotor neurons controlling non-shivering thermogenesis in brown adipose tissue (BAT) and thermoregulatory constriction of skin blood vessels, and also in a small population of tryptophan hydroxylase-positive serotonergic neurons. Intraperitoneal injection of diazepam, an anxiolytic agent, but not indomethacin, an antipyretic, significantly reduced both the stress-induced hyperthermia and Fos expression in these medullary raphe neuronal populations. Systemic blockade of beta3 -adrenoreceptors, which are abundantly expressed in BAT, also attenuated the stress-induced hyperthermia. These results suggest that psychological stress signals activate VGLUT3-expressing medullary raphe sympathetic premotor neurons, which then drive hyperthermic effector responses including BAT thermogenesis through beta(3) -adrenoreceptors. PMID- 21978216 TI - Correlations of properties and structures at different length scales of hydro- and organo-gels based on N-alkyl-(R)-12-hydroxyoctadecylammonium chlorides. AB - The self-assembly and gelating ability of a set of N-alkyl-(R)-12 hydroxyoctadecylammonium chlorides (NCl-n, where n = 0-6, 18 is the length of the alkyl chain on nitrogen) are described. Several are found to be ambidextrous (gelating both water and a variety of organic liquids) and very efficient (needing less than ca. 0.5 wt % at room temperature). Structure-property correlations at different distance scales of the NCl-n in their hydro- and organo gels and neat, solid states have been made using X-ray diffraction, neutron scattering, thermal, optical, cryo-SEM and rheological techniques. The self assembled fibrillar networks consist of spherulitic objects with fibers whose diameters and degrees of twisting differ in the hydro- and organo-gels. Increasing n (and, thus, the molecular length) increases the width of the fibers in their hydrogels; an irregular, less pronounced trend between n and fiber width is observed in the corresponding toluene gels. Time-dependent, small angle neutron scattering data for the isothermal sol-to-gel transformation of sols of NCl-18/toluene to their gels, treated according to Avrami theory, indicate heterogeneous nucleation involving rodlike growth. Rheological studies of gels of NCl-3 in water and toluene confirm their viscoelastic nature and show that the hydrogel is mechanically stronger than the toluene gel. Models for the different molecular packing arrangements within the fibrillar gel networks of the hydro- and organogels have been inferred from X-ray diffraction. The variations in the fibrillar networks provide a comprehensive picture and detailed insights into why seemingly very similar NCl-n behave very differently during their self-assembly processes in water and organic liquids. It is shown that the NCl-n provide a versatile platform for interrogating fundamental questions regarding the links between molecular structure and one-dimensional self-aggregation, leading to gelation. PMID- 21978217 TI - The interface between tradition and science: naturopaths' perspectives of modern practice. AB - OBJECTIVES: Although there has been much international commentary, little is known about the interface between traditional knowledge and scientific research in modern naturopathic practice. This study aimed to explore this interface from the perspective of naturopaths. DESIGN: Semistructured interviews were conducted with naturopaths in current practice. The participants were selected using purposive sampling, and the data from the interviews were interpreted using thematic analysis. SETTINGS/LOCATION: Interviews were conducted in a place suitable to each participant. SUBJECTS: Twelve (12) naturopaths in current clinical practice were interviewed. The participants represented a diversity of characteristics including gender, time in practice, level of qualification, and clinical contact hours per week. OUTCOME MEASURES: Thematic analysis was used to identify common themes from the interviews. RESULTS: Analysis identified a disparity in practitioner definition of what constitutes traditional information. However, it also identified that traditional knowledge is considered a valid source of information, whereas the validity and value of modern research is questioned. There is also tension between these two information sources, with science being argued to both support traditional knowledge, while also undermining its value. This tension seems to be overcome by practitioners' use of traditional knowledge to direct their own research, as well as drawing upon their knowledge of science to explain traditional knowledge as yet not researched. CONCLUSIONS: The findings of this qualitative study reveal tensions and ambiguities around the interface between tradition and science with regard to naturopathic clinical practice. Understanding these findings may assist individuals and groups within the naturopathic profession, as well as those outside the profession engaging and collaborating with naturopaths. PMID- 21978218 TI - What factors are influencing preferences toward conventional versus complementary and alternative medical clinic advertisements? AB - OBJECTIVES: The present study aimed to determine whether health service advertisements are perceived differently depending on advertising conventional or complementary and alternative medicine clinics. METHODS: A total of 42 adults (male=21, female=21) recruited through advertisements in Seoul, South Korea participated in this study. A standardized health service advertisement was designed with three controlled visual components such as (1) medical treatment information, (2) medical practitioner, and (3) medical facilities and it was shown to subjects while their eye movements were tracked and they were asked to rate their preferences for the different advertisements and their separate components. A multiple regression analysis was performed to see the correlation of the preferences for each of the three visual components with the overall preference rating of each health service advertisement. RESULTS: Preferences for the advertisement depended mostly on the preference for the medical treatment information, whereas advertisements for complementary and alternative medical clinics depended also on the preference for the medical practitioner. CONCLUSIONS: These results imply that the same health service advertisement will be perceived differently depending on whether it advertises Western or Oriental medical clinics. PMID- 21978219 TI - Radial pressure pulse and heart rate variability in normotensive and hypertensive subjects. AB - OBJECTIVES: The characteristics of the right/left radial pressure pulse (RPP) at the six diagnosis positions in Chinese medicine are not well documented. The purpose of this study is to investigate the spectral energy and augmentation index (AI) of bilateral RPP at the six diagnosis positions and heart rate variability (HRV) in the normotensives, hypertensives without heart dysfunction (HTN-N), and hypertensives with mild diastolic dysfunction (HTN-A). DESIGN: One hundred and thirty-eight (138) subjects were enrolled in this study. All subjects underwent measurements of brachial arterial blood pressure and RPP of both wrists while seated, and the supine measurement of HRV. AI and spectral energy of RPP as well as HRV were analyzed. RESULTS: The low-frequency component, the spectral HRV parameter, was significantly reduced in HTN-A compared with that in the normotensive group. Radial AI of the six diagnosis positions in HTN-N was significantly higher compared with that in the normotensive group or HTN-A. At the six diagnosis positions, the spectral energy of 0-10 Hz (SE(0-10 Hz)) in both hypertensive groups and 10-50 Hz (SE(10-50 Hz)) in the HTN-A group were significantly higher compared with those in the normotensive group. SE(10-50 Hz) at right Chy, left Chun, and left Guan in the HTN-N group were higher than those in the normotensive group. Within each group, there was a significant difference in the energy proportion, 10-50 Hz% (EP(10-50 Hz%)), between the six positions and a significant reduction only at the left Chun position in both hypertensive groups compared to that in the normotensive group. CONCLUSIONS: It is concluded that the EP(10-50 Hz%) revealed the specific characteristics of RPP and significantly varied at the six positions, and the left Chun position, the position to detect the heart diseases in Chinese medicine, is qualified to discriminate the differences between the normotensive and hypertensive patients. PMID- 21978220 TI - The effect of acupuncture on psychosocial outcomes for women experiencing infertility: a pilot randomized controlled trial. AB - OBJECTIVES: The study objectives were to examine the effectiveness of acupuncture for reducing infertility-related stress. DESIGN: The study design was a randomized controlled trial of acupuncture compared with a wait-list control. SETTING: The study was conducted at The University of Western Sydney. SUBJECTS: Thirty-two (32) women aged 20-45 years, with a diagnosis of infertility, or a history of unsuccessfully trying to conceive for 12 months or more, were the subjects of the study. INTERVENTIONS: Women received six sessions of acupuncture over 8 weeks. OUTCOME MEASURES: The primary outcomes were infertility self efficacy, anxiety, and infertility-related stress. The women's experience of infertility and acupuncture is also reported. RESULTS: At the end of the 8-week intervention, women in the acupuncture group reported significant changes on two domains on the Fertility Problem Inventory with less social concern (mean difference [MD] -3.75, 95% confidence interval [CI] -7.58 to 0.84, p=0.05), and less relationship concern (MD -3.66, 95% CI -6.80 to -0.052, p=0.02). There were also trends toward a reduction of infertility stress on other domains, and a trend toward improved self-efficacy (MD 11.9, 95% CI -2.20 to 26.0, p=0.09) and less anxiety (MD -2.54, 95% CI -5.95 to 0.86, p=0.08) in the acupuncture group compared with the wait-list control. Women described the experience and impact of acupuncture as positive relating to a sense of relaxation and time out, the engagement with the practitioner, and an intervention that had very few negative side-effects. Changes were also perceived after treatment with women describing a physical and psychologic sense of relaxation and calmness, and a changed perspective in relation to coping. CONCLUSIONS: Acupuncture may be a useful intervention to assist with the reduction of infertility-related stress. Further research is justified. PMID- 21978222 TI - Mechanism of membrane interaction and disruption by alpha-synuclein. AB - Parkinson's disease is a common progressive neurodegenerative condition, characterized by the deposition of amyloid fibrils as Lewy bodies in the substantia nigra of affected individuals. These insoluble aggregates predominantly consist of the protein alpha-synuclein. There is increasing evidence suggesting that the aggregation of alpha-synuclein is influenced by lipid membranes and, vice versa, the membrane integrity is severely affected by the presence of bound aggregates. Here, using the surface-sensitive imaging technique supercritical angle fluorescence microscopy and Forster resonance energy transfer, we report the direct observation of alpha-synuclein aggregation on supported lipid bilayers. Both the wild-type and the two mutant forms of alpha synuclein studied, namely, the familiar variant A53T and the designed highly toxic variant E57K, were found to follow the same mechanism of polymerization and membrane damage. This mechanism involved the extraction of lipids from the bilayer and their clustering around growing alpha-synuclein aggregates. Despite all three isoforms following the same pathway, the extent of aggregation and their effect on the bilayers was seen to be variant and concentration dependent. Both A53T and E57K formed cross-beta-sheet aggregates and damaged the membrane at submicromolar concentrations. The wild-type also formed aggregates in this range; however, the extent of membrane disruption was greatly reduced. The process of membrane damage could resemble part of the yet poorly understood cellular toxicity phenomenon in vivo. PMID- 21978221 TI - Effect of Traumeel S on cytokine profile in a cecal ligation and puncture (CLP) sepsis model in rats. AB - BACKGROUND: Sepsis results in significant morbidity and mortality, with current treatment options limited with respect to efficacy as well as safety. The complex homeopathic remedy Traumeel S has been shown to have both anti-inflammatory and immunostimulatory effects in the in vitro setting. OBJECTIVES: The objective was to explore the effects of Traumeel S in an in vivo setting, using a cecal ligation and puncture (CLP) sepsis model in rats, evaluating the effects of the medication on cytokine activity. DESIGN: Sepsis was induced in 30 rats using accepted CLP methodology. Following the procedure, rats were randomly allocated to receive an intraperitoneal injection of either Traumeel S (n=15) or normal saline (n=15). At 6 hours post-CLP, serum cytokines (interleukin [IL]-1beta, tumor necrosis factor-alpha, IL-6, and IL-10) were evaluated. RESULTS: IL-1beta levels were significantly higher in the treatment group (p=0.03) with no significant differences found between the groups with respect to the other cytokines tested. CONCLUSIONS: In contrast to in vitro studies, Traumeel significantly increased IL-1beta levels in an in vivo model, without influencing other cytokines. IL-1beta is a proinflammatory cytokine that has been shown to have a protective effect in the CLP rat model. Further research is warranted to examine this finding, as well as its clinical implications. PMID- 21978223 TI - Flavonoids in tropical citrus species. AB - HPLC with PDA and MS(2) detection was used to identify and quantify flavonoids in the tropical citrus species Citrus microcarpa , Citrus hystrix , Citrus medica var. 1 and 2, and Citrus suhuiensis . Most of these species contained high amounts of flavones, flavanones, and dihydrochalcone C- and/or O-glycosides, which were identified on the basis of HPLC retention times, cochromatography with available authentic standards, absorbance spectra, and mass spectral fragmentation patterns. Among the major compounds detected were apigenin-6,8-di-C glucoside, apigenin-8-C-glucosyl-2"-O-rhamnoside, phloretin-3',5'-di-C-glucoside, diosmetin-7-O-rutinoside, hesperetin-7-O-neohesperidoside, and hesperetin-7-O rutinoside. Most of the dihydrochalcone and flavone C-glycosides have not previously been detected in tropical citrus. C. microcarpa contained a high amount of phloretin-3',5'-di-C-glucoside. Most of the tropical citrus flavanones were neohesperidoside conjugates, which are responsible for imparting a bitter taste to the fruit. Only C. suhuiensis fruit contains rutinoside, a nonbitter conjugate. PMID- 21978225 TI - Synthesis, biological activities and bioavailability of moschamine, a safflomide type phenylpropenoic acid amide found in Centaurea cyanus. AB - Moschamine is a phenylpropenoic acid amide found in plants. In this article, the synthesis and two biological activities (serotoninergic and cyclooxygenase (COX) inhibitory activities) and bioavailability of moschamine were described. Moschamine was synthesised and confirmed using NMR spectroscopic methods. Using the moschamine synthesised, serotoninergic and COX inhibitory activities were investigated. At the concentration of 10 umol L-1, moschamine was able to inhibit forskolin-stimulated cAMP formation by 25% (p < 0.015), via inhibiting serotonin receptors in the OK cells. The inhibition was repressed by two 5-HT1 antagonists (Nan-190 and spiperone), suggesting that moschamine may suppress cAMP formation via binding to 5-HT1 receptors in the cells. Also, moschamine was a very potent compound that is able to inhibit COX-I by 58% (p < 0.012) and COX-II by 54% (p < 0.014), at the concentration of 0.1 umol L-1. The oral bioavailability of moschamine was also determined in mice. PMID- 21978224 TI - Smoking and other factors associated with short-term partial remission of Type 1 diabetes in adults. AB - AIMS: The duration of partial remission of Type 1 diabetes is associated with the degree of initial metabolic disturbance and features of insulin resistance. Cigarette smoking decreases insulin sensitivity, but its influence on the length of remission is unknown. Therefore, this study assessed the relationship between cigarette smoking and duration of partial remission in adults with newly diagnosed Type 1 diabetes. METHODS: We recruited 149 patients (48 women and 101 men, aged 16-35 years, median age 25 years), admitted to a teaching hospital with newly diagnosed Type 1 diabetes and followed them for a median period of 1 year and 9 months. We introduced intensive insulin therapy in multiple injections (basal-bolus) in all patients. We defined partial remission as an insulin dose of <= 0.3 U/kg body weight/24 h, an HbA(1c) value < 53 mmol/mol (7.0%) and a random serum C-peptide concentration over 0.5 ng/ml. Cigarette smoking was determined by self-report. RESULTS: Of 149 patients, 68 (46%) fulfilled the criteria for partial remission at 1 year after diagnosis of diabetes. Fewer patients who were in partial remission at 1 year smoked (19/68, 28%) than did patients that were not in partial remission (41/81, 51%). In logistic regression analyses, non smoking was associated with remission at 1 year independent of age, sex, HbA(1c) and presence of diabetic ketoacidosis, all measured at onset of diabetes (OR 3.32, 95% CI 1.42-7.75, P = 0.005). CONCLUSION: Relative to individuals in this study who smoked, those who did not smoke at diagnosis of Type 1 diabetes experienced a longer duration of partial remission. PMID- 21978230 TI - Fabrication of periodic metal nanowires with microscale mold by nanoimprint lithography. AB - In this paper, a simple method is demonstrated for fabricating periodic metal nanowires based on the unconventional nanoimprint lithography (NIL) technique. Using this method, sub-100 nm metal nanowires with the rectangular cross-section are fabricated with microscale stamp. Furthermore, the metal nanowires with different widths and heights can be generated by adjusting the imprinting parameters with the same stamp. The metal nanowires prepared with this method can be used for chemical sensing, such as ammonia sensing, and it may have applications in optical signal processing. PMID- 21978231 TI - Tumor of the pituitary. PMID- 21978232 TI - Concomitant asthma medication use in patients receiving omalizumab: results from three large insurance claims databases. AB - BACKGROUND: Omalizumab (Xolair(r)) is a monoclonal antibody indicated for moderate to severe persistent allergic asthma patients with symptoms that are inadequately controlled with inhaled corticosteroids (ICS). OBJECTIVE: This study describes concomitant asthma medication use in patients treated with omalizumab. METHODS: An analysis of health insurance claims from MarketScan (2002-2009), Medicaid (2002-2009), and the HealthCore Integrated Research Database (HIRDTM) (2002-2010) was conducted. Medical charts were also extracted for a subset of HIRD patients. Patients aged >=12 years and newly initiated on omalizumab with 12 months of continuous insurance coverage prior to the first omalizumab dispensing (baseline period) and >=2 asthma claims were included. Concomitant asthma medication use was summarized in eight medication classes. RESULTS: A total of 6038 patients were identified (Medicaid: 731; MarketScan: 3521; HIRD: 1786). A high proportion of new omalizumab users had an asthma-related emergency room visit (Medicaid: 34%; MarketScan: 17%; HIRD: 16%) or hospitalization (Medicaid: 36%; MarketScan: 14%; HIRD: 21%) within 12 months prior to initiating omalizumab. Most patients (Medicaid: 96%; MarketScan: 89%; HIRD: 86%) received three concomitant asthma medication classes or more during the baseline period. Concomitant ICS use was observed in 95%, 89%, and 86% of Medicaid, MarketScan, and HIRD patients, respectively. In HIRD patients without evidence of receiving other asthma medication prior to omalizumab, 17 out of 20 patients had a documented baseline history of asthma-related medication use in their medical charts. CONCLUSIONS: This large observational study using health insurance claims from three databases and confirming results from medical charts provides evidence that nearly all omalizumab users had received other asthma medications prior to initiating omalizumab. PMID- 21978233 TI - Use of virtual reality in rehabilitation of movement in children with hemiplegia- a multiple case study evaluation. AB - PURPOSE: To evaluate the feasibility and therapeutic effect of engaging children of differing neuromotor and cognitive ability in a virtual reality (VR) tabletop workspace designed to improve upper-limb function. METHOD: Single-subject experimental design with multiple baselines was employed. Four children with hemiplegia participated in VR-based training between nine and 19, 30-minute sessions, over three-four weeks. Outcomes were assessed from the perspective of the International Classification of Functioning, Disability and Health; considering body function, activity performance and participation. Upper-limb performance was assessed using system-measured variables (speed, trajectory and accuracy) and standardized tests. Trend analyses were employed to determine trends on system variables between baseline phase and treatment phases. Standardised measures were compared between pre- and post-training. RESULTS: Two children made progress across system variables with some translation to daily activities. Performance of the other two children was more variable, however, they engaged positively with the system by the end of the treatment phase. CONCLUSIONS: The VR (RE-ACTION) system shows promise as an engaging rehabilitation tool to improve upper-limb function of children with hemiplegia, across ability levels. Trade-offs between kinematic variables should be considered when measuring improvements in movement skill. Larger trials are warranted to evaluate effects of augmented feedback, intensity and duration of training, and interface type to optimise the system's effectiveness. PMID- 21978234 TI - Climate change and community disassembly: impacts of warming on tropical and temperate montane community structure. AB - Both tropical and temperate species are responding to global warming through range shifts, but our understanding of the consequences of these shifts for whole communities is limited. Here, we use current elevational range data for six taxonomic groups spanning 90 degrees in latitude to examine the potential impacts of climate-driven range shifts on community change, or 'disassembly', across latitude. Elevational ranges are smaller at low latitudes for most groups and, as a consequence, tropical communities appear to be more sensitive to temperature increases compared with temperate communities. Under site-specific temperature projections, we generally found greater community disassembly in tropical compared with temperate communities, although this varied by dispersal assumptions. Mountain height can impact the amount of community disassembly, with greater change occurring on smaller mountains. Finally, projected community disassembly was higher for ectotherms than endotherms, although the variation among ectotherms was greater than the variation separating endotherms and ectotherms. PMID- 21978235 TI - Do non-steroidal anti-inflammatory drugs delay posterior capsule opacification after phacoemulsification in children? A randomized, prospective controlled trial. AB - PURPOSE: To evaluate the efficacy of topical ketorolac for the prevention of posterior capsule opacification (PCO) in pediatric cataract surgery. MATERIALS AND METHODS: The eyes were prospectively and randomly assigned to receive postoperative 3-month topical ketorolac 0.5% drops with intact posterior capsule (group 1) or primary posterior capsulotomy combined with anterior vitrectomy (group 2). All children had uneventful corneal small-incision phacoemulsification with a primary implantation of a foldable acrylic posterior chamber intraocular lens (IOL). The frequency and timing of severe PCO was evaluated for each group and documented by slit-lamp examination and photography. RESULTS: A total of 38 eyes of 27 children (15 girls, 12 boys) were included in the study. Among them 16 children had unilateral and 11 had bilateral surgery. All cataracts were developmental cases diagnosed between 1 and 7 years of age. There were 20 eyes in group 1 and 18 eyes in group 2. Mean pediatric age at surgery was 38.1 months (12 72 months) in group 1 and 34.2 months in group 2 children (12-78 months) (p>0.05). Overall mean follow up was 26.3 months (6-48 months). Clinically significant PCO that finally needed neodymium:YAG laser application developed in four eyes (20.0%) in group 1 and in two eyes (11.1%) in group 2, and the difference was not statistically significant (chi-square test, p >0.05). CONCLUSIONS: Long-term postoperative use of topical ketorolac drops with the preservation of posterior capsule was found to be effective for the prevention of PCO in pediatric cataract surgery, at least during the period of this study. PMID- 21978236 TI - Polymer-grafted-nanoparticle surfactants. AB - We have studied the surface behavior of nanoparticles, which are lightly grafted with polymer chains, when they are mixed with matrix chains of the same architecture as the grafts. We consider the particular case where the nanoparticle core and the grafted polymer chains energetically dislike each other and show that the extent of surface segregation of these "hairy" nanoparticles and their self-assembly into a variety of structures can be tuned by varying the number and the length of the grafted chains and the matrix chain length. These results unequivocally show that grafted nanoparticles in polymer matrices behave akin to block copolymers (or amphiphiles) in selective solvents, with readily controllable surface behavior. PMID- 21978237 TI - Maternal obesity trends in Egypt 1995-2005. AB - According to the World Health Organization (WHO), 46% of adult females in Egypt are obese. This research was aimed at documenting obesity trends and identifying the populations most at risk for obesity. Using data from the 1995 and 2005 Egyptian Demographic and Health Surveys a linear model was employed to seek associations between household wealth, urban/rural residence, governorate of residence, employment status, parity and age and increases in body mass index (BMI) among married Egyptian women between the ages of 15-49. Between 1995 and 2005, the mean BMI of women of reproductive age in Egypt increased from 26.31 to 28.52. Although there was an overall trend towards greater obesity between 1995 and 2005, older women residing in rural, poor households became obese at a faster rate than younger women residing in richer, urban households. Studies have shown that household wealth is a key determinant of food consumption patterns. Rising obesity rates among the poor in developed countries are linked to the relatively cheap price of high-calorie, nutrient-poor foods. One factor that may be contributing to the rapid increases in obesity among the rural poor in Egypt is the subsidisation of high-energy, low-nutritive value foods that form a larger part of the diet of poor, rural populations. PMID- 21978238 TI - Treatment guided by rapid diagnostic tests for malaria in Tanzanian children: safety and alternative bacterial diagnoses. AB - BACKGROUND: WHO guidelines for the treatment of young children with suspected malaria have recently changed from presumptive treatment to anti-malarial treatment guided by a blood slide or malaria rapid diagnostic test (RDT). However, there is limited evidence of the safety of this policy in routine outpatient settings in Africa. METHODS: Children 3-59 months of age with a non severe febrile illness and no obvious cause were enrolled over a period of one year in a malaria endemic area of Tanzania. Treatment was determined by the results of a clinical examination and RDT result, and blood culture and serum lactate were also collected. RDT-negative children were followed up over 14 days. RESULTS: Over the course of one year, 965 children were enrolled; 158 (16.4%) were RDT-positive and treated with artemether-lumefantrine and 807 (83.4%) were RDT-negative and treated with non-anti-malarial medicines. Compared with RDT positives, RDT-negative children were on average younger with a lower axillary temperature and more likely to have a history of cough or difficulty in breathing. Six (0.6%) children became RDT-positive after enrollment, all of whom were PCR-negative for Plasmodium falciparum DNA at enrollment. In addition, 12 (1.2%) children were admitted to hospital, one with possible malaria, none of whom died. A bacterial pathogen was identified in 9/965 (0.9%) children, eight of whom were RDT-negative and one was RDT-positive, but slide-negative. Excluding three children with Salmonella typhi, all of the children with bacteraemia were <= 12 months of age. Compared to double-read research slide results RDTs had a sensitivity of 97.8% (95% CI 96.9-98.7) and specificity of 96.3% (95% CI 96.3 98.4). CONCLUSIONS: Use of RDTs to direct the use of anti-malarial drugs in young children did not result in any missed diagnoses of malaria although new infections soon after a consultation with a negative RDT result may undermine confidence in results. Invasive bacterial disease is uncommon in children with non-severe illness and most cases occurred in infants with a current fever. PMID- 21978239 TI - Toxicity of multiwalled carbon nanotubes with end defects critically depends on their functionalization density. AB - Carboxylated carbon nanotubes stand as the most promising nanovectors for biomedical and pharmaceutical applications due to their ease of covalent conjugation with eclectic functional molecules including therapeutic drugs, proteins, and oligonucleotides. In the present study, we attempt to investigate how the toxicity of acid-oxidized multiwalled carbon nanotubes (MWCNTs) can be tweaked by altering their degree of functionalization and correlate the toxicity trend with their biodistribution profile. In line with that rationale, mice were exposed to 10 mg/kg of pristine (p) and acid-oxidized (f) MWCNTs with varying degrees of carboxylation through a single dose of intravenous injection. Thereafter, extensive toxicity studies were carried out to comprehend the short term (7 day) and long-term (28 day) impact of p- and various f-MWCNT preparations on the physiology of healthy mice. Pristine MWCNTs with a high aspect ratio, surface hydrophobicity, and metallic impurities were found to induce significant hepatotoxicity and oxidative damage in mice, albeit the damage was recovered after 28 days of treatment. Conversely, acid-oxidized carboxylated CNTs with shorter lengths, hydrophilic surfaces, and high aqueous dispersibility proved to be less toxic and more biocompatible than their pristine counterparts. A thorough scrutiny of various biochemical parameters, inflammation indexes, and histopathological examination of liver indicated that toxicity of MWCNTs systematically decreased with the increased functionalization density. The degree of shortening and functionalization achieved by refluxing p-MWCNTs with strong mineral acids for 4 h were sufficient to render the CNTs completely hydrophilic and biocompatible, while inducing minimal hepatic accumulation and inflammation. Quantitative biodistribution studies in mice, intravenously injected with Tc-99m labeled MWCNTs, clearly designated that clearance of CNTs from reticuloendothelial system (RES) organs such as liver, spleen, and lungs was critically functionalization density dependent. Well-individualized MWCNTs with shorter lengths (<500 nm) and higher degrees of oxidation (surface carboxyl density >3 MUmol/mg) were not retained in any of the RES organs and rapidly cleared out from the systematic circulation through renal excretion route without inducing any obvious nephrotoxicity. As both p- and f-MWCNT-treated groups were devoid of any obvious nephrotoxicity, CNTs with larger dimensions and lower degrees of functionalization, which fail to clear out from the body via renal excretion route, were thought to be excreted via biliary pathway in faeces. PMID- 21978241 TI - Effects of electromyostimulation on knee extensors and flexors strength and steadiness in older adults. AB - It is known that electromyostimulation (EMS) alone or superimposed over voluntary contraction (EV) can effectively improve muscle strength. However, the effect of this type of training on the ability to control force production at submaximal levels is unknown. The authors examined the effects of EV training on steadiness in force production of knee extensors and flexors in older adults. Forty participants, including 20 men and 20 women, 60-77 years of age, were randomly allocated into a control group (CG) and an electromyostimulation superimposed over voluntary contraction (EVG) group. The EVG performed 30 bilateral isometric knee extension and flexion contractions per session, 3 training sessions per week, for 6 weeks. The variations in force production, expressed in absolute (standard deviation [SD]) and relative (coefficient of variation [CV]) terms, were assessed in isometric contractions at 5%, 15% and 25% maximal voluntary contraction (MVC) levels. Results indicated that MVC increased in knee extension and flexion in EVG (p < .05) after the training; steadiness CV also improved at 15% MVC in knee flexion (p < .05) but no significant changes were found in knee extension and steadiness SD. The training-induced changes in MVC were not correlated to steadiness CV that might indicate different mechanisms underlying these adaptations. PMID- 21978240 TI - Effects of elevated seawater pCO(2) on gene expression patterns in the gills of the green crab, Carcinus maenas. AB - BACKGROUND: The green crab Carcinus maenas is known for its high acclimation potential to varying environmental abiotic conditions. A high ability for ion and acid-base regulation is mainly based on an efficient regulation apparatus located in gill epithelia. However, at present it is neither known which ion transport proteins play a key role in the acid-base compensation response nor how gill epithelia respond to elevated seawater pCO(2) as predicted for the future. In order to promote our understanding of the responses of green crab acid-base regulatory epithelia to high pCO(2), Baltic Sea green crabs were exposed to a pCO(2) of 400 Pa. Gills were screened for differentially expressed gene transcripts using a 4,462-feature microarray and quantitative real-time PCR. RESULTS: Crabs responded mainly through fine scale adjustment of gene expression to elevated pCO(2). However, 2% of all investigated transcripts were significantly regulated 1.3 to 2.2-fold upon one-week exposure to CO(2) stress. Most of the genes known to code for proteins involved in osmo- and acid-base regulation, as well as cellular stress response, were were not impacted by elevated pCO(2). However, after one week of exposure, significant changes were detected in a calcium-activated chloride channel, a hyperpolarization activated nucleotide-gated potassium channel, a tetraspanin, and an integrin. Furthermore, a putative syntaxin-binding protein, a protein of the transmembrane 9 superfamily, and a Cl(-)/HCO(3)(-) exchanger of the SLC 4 family were differentially regulated. These genes were also affected in a previously published hypoosmotic acclimation response study. CONCLUSIONS: The moderate, but specific response of C. maenas gill gene expression indicates that (1) seawater acidification does not act as a strong stressor on the cellular level in gill epithelia; (2) the response to hypercapnia is to some degree comparable to a hypoosmotic acclimation response; (3) the specialization of each of the posterior gill arches might go beyond what has been demonstrated up to date; and (4) a re configuration of gill epithelia might occur in response to hypercapnia. PMID- 21978242 TI - Long-term risk of recurrent stroke in young cryptogenic stroke patients with and without patent foramen ovale. AB - BACKGROUND: Among patients with a patent foramen ovale and cryptogenic ischemic stroke, the long-term prognosis is unclear. AIMS: This study aims to estimate the recurrence rate in young cryptogenic stroke patients with and without patent foramen ovale. PATIENTS AND METHODS: One hundred eighty-six cryptogenic stroke patients (aged 18-45 years) were prospectively followed for up to five-years. They were divided into two groups according to the echocardiographic presence of patent foramen ovale. All patients received aspirin (100 mg/day) for secondary prevention. RESULTS: Mean age was 32.3 (standard deviation 7.9) years. During the mean follow-up of 66 months five patients with patent foramen ovale had recurrent strokes compared with 11 patients without patent foramen ovale. The average annual rate of recurrent cerebral ischemia was 1.1% and 1.6% for patients with and without patent foramen ovale, respectively. The recurrence rate did not increase with the presence of patent foramen ovale, atrial septal aneurysm or other variables. More than 60% of the reported cases achieved a good functional outcome. CONCLUSIONS: Young patients with cryptogenic ischemic stroke with and without patent foramen ovale have a low recurrence rate in a long-term follow-up and most present a favorable outcome. Patent foramen ovale with or without atrial septal aneurysm did not increase the risk of recurrence. PMID- 21978243 TI - Review article: current antiviral therapy of chronic hepatitis B. AB - BACKGROUND: The indications and endpoints for treatment of chronic hepatitis B continue to evolve. The aim of the therapy for chronic hepatitis B is to achieve a long-term continued suppression of the hepatitis B virus (HBV) DNA to prevent disease progression leading to the development of cirrhosis and hepatocellular carcinoma. AIM: To summarise current literature on therapy of chronic hepatitis B, with a focus on indications for therapy, preferred treatment options, and management of resistance and partial responders. METHODS: A systematic review of the literature, with a focus on international guidelines, was performed. RESULTS: Seven drugs are licensed for the treatment of chronic hepatitis B in many countries. The selection of a drug with high potency and low rate of resistance is essential to achieve rapid and long-term viral suppression. The prevention of the sequelae of antiviral drug resistance and appropriate management of viral breakthrough are major goals of current management. The addition or change to an antiviral agent that is not cross-resistant is critical to restore suppression of viral replication for patients with breakthrough resistance. Patient adherence to medication is essential to achieve adequate HBV DNA suppression. CONCLUSIONS: The current treatment strategy of chronic hepatitis B is now standard: initial selection of entecavir, tenofovir, or peginterferon alfa-2a. Future studies are required to determine if combination therapy using two oral agents or peginterferon with an oral agent with a high genetic barrier to resistance might be superior to standard current monotherapy. PMID- 21978244 TI - Quality of life and functionality after total hip arthroplasty: a long-term follow-up study. AB - BACKGROUND: There is a lack of data on the long-term outcome of total hip arthroplasty procedures, as assessed by validated tools. METHODS: We conducted a follow-up study to evaluate the quality of life and functionality of 250 patients an average of 16 years (range: 11-23 years) after total hip arthroplasty using a validated assessment set including the SF-36 questionnaire, Harris Hip Score, WOMAC score, Functional Comorbidity Index, and a study specific questionnaire. Models of multiple stepwise linear and logistic regression analysis were constructed to evaluate the relationships between several explanatory variables and these functional outcomes. RESULTS: The SF-36 physical indexes of these patients compared negatively with the normative values but positively with the results obtained in untreated subjects with severe hip osteoarthritis. Similar results were detected for the Harris Hip Score and WOMAC score. There was a 96% rate of post-surgical satisfaction. Hip functionality and comorbidities were the most important determinants of physical measures on the SF-36. CONCLUSIONS: Patients who had undergone total hip arthroplasty have impaired long-term self reported physical quality of life and hip functionality but they still perform physically better than untreated patients with advanced hip osteoarthritis. However, the level of post-surgical satisfaction is high. PMID- 21978245 TI - Arbuscule-containing and non-colonized cortical cells of mycorrhizal roots undergo extensive and specific reprogramming during arbuscular mycorrhizal development. AB - Most vascular plants form a mutualistic association with arbuscular mycorrhizal (AM) fungi, known as AM symbiosis. The development of AM symbiosis is an asynchronous process, and mycorrhizal roots therefore typically contain several symbiotic structures and various cell types. Hence, the use of whole-plant organs for downstream analyses can mask cell-specific variations in gene expression. To obtain insight into cell-specific reprogramming during AM symbiosis, comparative analyses of various cell types were performed using laser capture microdissection combined with microarray hybridization. Remarkably, the most prominent transcriptome changes were observed in non-arbuscule-containing cells of mycorrhizal roots, indicating a drastic reprogramming of these cells during root colonization that may be related to subsequent fungal colonization. A high proportion of transcripts regulated in arbuscule-containing cells and non arbuscule-containing cells encode proteins involved in transport processes, transcriptional regulation and lipid metabolism, indicating that reprogramming of these processes is of particular importance for AM symbiosis. PMID- 21978246 TI - Approval times for a multi-centre diabetes study in UK primary care. PMID- 21978247 TI - Exploring symmetry as an avenue to the computational design of large protein domains. AB - It has been demonstrated previously that symmetric, homodimeric proteins are energetically favored, which explains their abundance in nature. It has been proposed that such symmetric homodimers underwent gene duplication and fusion to evolve into protein topologies that have a symmetric arrangement of secondary structure elements--"symmetric superfolds". Here, the ROSETTA protein design software was used to computationally engineer a perfectly symmetric variant of imidazole glycerol phosphate synthase and its corresponding symmetric homodimer. The new protein, termed FLR, adopts the symmetric (betaalpha)(8) TIM-barrel superfold. The protein is soluble and monomeric and exhibits two-fold symmetry not only in the arrangement of secondary structure elements but also in sequence and at atomic detail, as verified by crystallography. When cut in half, FLR dimerizes readily to form the symmetric homodimer. The successful computational design of FLR demonstrates progress in our understanding of the underlying principles of protein stability and presents an attractive strategy for the in silico construction of larger protein domains from smaller pieces. PMID- 21978248 TI - An 11-year-old girl with polyuria, polydipsia and skull lesion. PMID- 21978249 TI - Structure, sodium ion role, and practical issues for beta-alumina as a high-k solution-processed gate layer for transparent and low-voltage electronics. AB - Sodium beta-alumina (SBA)-based gate dielectric films have been developed for all solution-processed, transparent and low voltage field-effect transistors (FETs). Its high dielectric constant has been ascribed to sodium (Na+) ions in the crystal structure; however, there are no published experimental results concerning the contribution of Na+ ions to the dielectric behavior, and the degree of crystallinity of the thin films. In addition, as an ionic conductor, beta-alumina could give rise to some issues such as leakage current caused by Na diffusion, threshold voltage shift due to interface charge accumulation and longer response time due to slower polarization of the Na+ ions. This paper will address these issues using zinc tin oxide (ZTO) FETs, and propose possible measures to further improve SBA-based gate materials for electronic devices. PMID- 21978252 TI - Easy cleaning of the camera port during laparoscopic surgery: three practical techniques. AB - Bad vision due to a dirty camera lens is one of the disadvantages and one of the most prominent frustrations in performing endoscopic surgery. Different methods to prevent lens fogging have been described; however, little is published about the prevention of lens contamination due to a dirty port. The authors report three port-cleaning methods: (1) sterile gauze wrapped around an endoscopic dissecting clamp, (2) sterile gauze wrapped around a Pean clamp, and (3) a 10-mm sterile cotton swab, all being simple, adequate, cost-saving solutions. PMID- 21978253 TI - Laparoscopic resection of a giant solid pseudopapillary neoplasm of uncinate process of the pancreas in a child. AB - Solid pseudopapillary neoplasm of the pancreas in children is rare, and the most common localization of the tumor is the tail. The authors encountered such a case in a 10-year-old girl with a giant solid pseudopapillary neoplasm at the uncinate process of the pancreas. Imaging examination showed there was a distinct distance between the neoplasm and the main pancreatic duct. Using a 4-port transperitoneal laparoscopic technique, complete resection of the tumor was successfully performed. Laparoscopic approach appears to be safe and feasible in children with solid pseudopapillary neoplasm, and an organ-preservation operation can be successfully performed if there is no communication between the tumor and the pancreatic ductal system. PMID- 21978254 TI - Anti-cholinergic effect of Zataria multiflora Boiss on guinea pig tracheal chains. AB - The effects of three concentrations of aqueous-ethanolic extract, 10 nM atropine and saline on muscarinic receptors were tested on two groups of non-incubated (group 1; n = 7) and incubated tracheal chains with propranolol and chlorpheniramine (group 2; n = 6). The EC50 of higher concentration of the extract (2 ug mL-1) in group 2 was significantly greater than those of group 1 (p < 0.01). The maximum response obtained in the presence of all concentrations of extract in groups 1 and 2 were lower than saline (p < 0.05 to 0.001). There were parallel rightward shifts in the concentration response curves obtained for all concentrations of the extract in group 2. There was significant and positive correlation between the concentrations and the values of EC50 in group 1 (p < 0.05) and group 2 (p < 0.001). These results indicate an anti-cholinergic effect of Zataria multiflora Boiss on the tracheal chains of guinea pigs. A beta adrenoceptor stimulatory effect for the plant was also suggested. PMID- 21978255 TI - Determining membrane capacitance by dynamic control of droplet interface bilayer area. AB - By making dynamic changes to the area of a droplet interface bilayer (DIB), we are able to measure the specific capacitance of lipid bilayers with improved accuracy and precision over existing methods. The dependence of membrane specific capacitance on the chain-length of the alkane oil present in the bilayer is similar to that observed in black lipid membranes. In contrast to conventional artificial bilayers, DIBs are not confined by an aperture, which enables us to determine that the dependence of whole bilayer capacitance on applied potential is predominantly a result of a spontaneous increase in bilayer area. This area change arises from the creation of new bilayer at the three phase interface and is driven by changes in surface tension with applied potential that can be described by the Young-Lippmann equation. By accounting for this area change, we are able to determine the proportion of the capacitance dependence that arises from a change in specific capacitance with applied potential. This method provides a new tool with which to investigate the vertical compression of the bilayer and understand the changes in bilayer thickness with applied potential. We find that, for 1,2-diphytanoyl-sn-glycero-3-phosphocholine membranes in hexadecane, specific bilayer capacitance varies by 0.6-1.5% over an applied potential of +/-100 mV. PMID- 21978256 TI - Mining the ChEMBL database: an efficient chemoinformatics workflow for assembling an ion channel-focused screening library. AB - The ChEMBL database was mined to efficiently assemble an ion channel-focused screening library. The compiled library consists of 3241 compounds representing 123 templates across nine ion channel categories. Compounds in the screening library are annotated with their respective ion channel category to facilitate back-tracing of prospective molecular targets from phenotypic screening results. The established workflow is adaptable to the construction of focused screening libraries for other therapeutic target classes with diverse recognition motifs. PMID- 21978257 TI - Paleolithic spread of Y-chromosomal lineage of tribes in eastern and northeastern India. AB - BACKGROUND: The Indian peninsula provides a suitable region for examination of the demographic impact of migrations and invasions in historical times, because its complex recent history has involved the long-term residence of different populations with distinct geographical origins and their own particular cultural characteristics. AIM: The aim of the present study was to analyse Y chromosome haplotypes in tribes from eastern and north-eastern India, which provided the necessary phylogeographic resolution. SUBJECTS AND METHODS: A total of 32 Y chromosome SNPs and 17 Y-STRs were genotyped in 607 males from nine populations (Munda, Birhor, Oraon, Paharia, Santhal, Ho, Lachung, Mech and Rajbanshi) residing in East and Northeastern India. RESULTS: Y-chromosomal analysis revealed high frequency of the O2a haplogroup in Austroasiatic tribes and high haplotype diversity within specific haplogroups demonstrating a lesser degree of admixture of these populations with neighbouring populations in eastern India. In addition, the presence of O3a haplogroups in Sino-Tibetan populations reflects the influx from Southeast Asia during the demographic expansion through the Northeastern corridor. CONCLUSION: The study suggested that the majority of the male gene flow of Austroasiatic tribes occurred during the late Pleistocene period. The results suggest gene flow from Southeast Asia to Northeast India, albeit more significantly among Tibeto-Burman than Austroasiatic-speaking populations. PMID- 21978258 TI - Theoretical study on the alkaline hydrolysis of methyl thioacetate in aqueous solution. AB - A base-catalyzed hydrolysis reaction of thiolester has been studied in both gas and solution phases using two ab initio quantum mechanics calculations such as Gaussian09 and CPMD. The free-energy surface along the reaction path is also constructed using a configuration sampling technique, namely, the metadynamics method. While there are two different reaction paths obtained for the potential profile of the base-catalyzed hydrolysis reaction for thiolester in the gas phase, a triple-well reaction path is computed for the reaction in the solution phase by two quantum mechanics calculations. Unlike the S(N)2 mechanism (a concerted mechanism) found for the gas-phase reaction, a nucleophilic attack from the hydroxide ion on the carbonyl carbon to yield a tetrahedral intermediate (a stepwise mechanism) is observed for the solution-phase reaction. Moreover, the energy profiles computed by these two theoretical calculations are found to be very comparable with those determined experimentally. PMID- 21978259 TI - Fatigue after stroke: frequency and effect on daily life. AB - PURPOSE: An audit was conducted to assess the frequency of fatigue after stroke, to determine the impact on daily life, and whether it was discussed with clinicians. METHOD: Patients were recruited from Nottingham University Hospitals NHS Trust stroke service. Patients were interviewed about their fatigue, and the Fatigue Severity Subscale (FSS-FAI), Brief Assessment Schedule for Depression Cards (BASDEC), Barthel Index and Nottingham Extended Activities of Daily Living (EADL) Scale were administered. RESULTS: 64 patients were recruited, with a mean age 73.5 years (SD 14.0, range 37-94 years), 37 (58%) as in-patients and 27 (42%) as outpatients. There were 41 (64%) who reported significant levels of fatigue and 31 (48%) with significant fatigue on the Fatigue Severity Scale. Demographic and clinical variables were not significantly related to fatigue (p > 0.05), apart from gender, with women reporting significantly more fatigue than men (p = 0.006). There was a moderate correlation between the BASDEC and FSS (r(s) = 0.41, p = 0.002). Of the 41 participants who reported fatigue, 33 (81%) had not discussed this with their clinician. CONCLUSIONS: Fatigue was a common problem after stroke. There was a lack of awareness in both patients and clinicians and little advice being given to patients with fatigue. PMID- 21978261 TI - Relationship of CD34+ cells infused and red blood cell transfusion requirements after autologous peripheral blood stem cell transplants: a novel method of analysis. AB - BACKGROUND: CD34+ cells infused predicts myeloid and platelet engraftment at the time of autologous stem cell transplantation. An association between the number of CD34+ cells infused and erythroid engraftment has yet to be established. STUDY DESIGN AND METHODS: Red blood cells transfused after autologous transplantation were compared with the number of CD34+ cells infused. Myeloid engraftment was assessed to confirm that normal engraftment kinetics occurred. RESULTS: Logistic regression established that the logarithm of the number of CD34+ cells infused (p = 0.0498) and admission hemoglobin (Hb; p < 0.001) predicted the need for transfusion. In those patients who required transfusion, standard regression methods were not valid. A novel model demonstrated that the initial Hb (p < 0.001) and diagnosis (p = 0.047) were significant predictors of transfusion requirements in patients needing transfusion. However, the number of CD34+ cells infused did not predict transfusion requirements in this group (p = 0.226). As myeloid engraftment demonstrated kinetics that have been previously described, it can be inferred that erythroid engraftment was not atypical. CONCLUSION: The number of CD34+ cells infused predicted the need for transfusion, although it did not predict the number of RBCs transfused in those patients having transfusion during their admission for autologous stem cell transplant. PMID- 21978260 TI - Cell-penetrating peptides, PepFects, show no evidence of toxicity and immunogenicity in vitro and in vivo. AB - Cell-penetrating peptide based vehicles have been developed for the delivery of different payloads into the cells in culture and in animals. However, several biological features, among which is the tendency to trigger innate immune response, limit the development of highly efficient peptide-based drug delivery vectors. This study aims to evaluate the influence of transportan 10 (TP10) and its chemically modified derivatives, PepFects (PFs), on the innate immune response of the host system. PFs have shown high efficiency in nucleic acid delivery in vitro and in vivo; hence, the estimation of their possible toxic side effects would be of particular interest. In this study, we analyzed cytotoxic and immunogenic response of PF3, PF4, and PF6 peptides in monocytic leukemia and peripheral blood mononuclear cell lines. In comparison with amphipathic PFs, TP10, TAT, stearyl-(RxR)(4) peptides, and the most widely used transfection reagents Lipofectamine 2000 and Lipofectamine RNAiMAX were also analyzed in this study. IL-1beta, IL-18, and TNF-alpha cytokine release was detected using highly sensitive enzyme-linked immunosorbent assay (ELISA). Cell viability was detected by measuring the activity of cellular enzymes that reduce water-soluble tetrazolium salts to formazan dyes and apoptosis was evaluated by measuring the levels of caspase-1 and caspase-3/7 over untreated cells. All peptides were found to be nontoxic and nonimmunogenic in vitro at the concentrations of 10 MUM and 5 MUM, respectively, and at a dose of 5 mg/kg in vivo, suggesting that these CPPs exhibit a promising potential in the delivery of therapeutic molecules into the cell without risks of toxicity and inflammatory reactions. PMID- 21978262 TI - First direct evidence of radical intermediates in samarium diiodide induced cyclization by ESR spectra. AB - The mechanism of samarium diiodide (SmI(2))-induced cyclization of alpha,beta unsaturated esters and ketones to bicyclic compounds was examined using ESR spectroscopy. This is the first report of direct evidence of the radical intermediates in the SmI(2) reaction. The preferential reduction of the alpha,beta-unsaturated carbonyl part in some substrates should be recognized as a main route. PMID- 21978264 TI - Constraints on arm selection processes when reaching: degrees of freedom and joint amplitudes interact to influence limb selection. AB - With an interest in identifying the variables that constrain arm choice when reaching, the authors had 11 right-handed participants perform free-choice and assigned-limb reaches at 9 object positions. The right arm was freely selected 100% of the time when reaching to positions at 30 degrees and 40 degrees into right hemispace. However, the left arm was freely selected to reach to positions at -30 degrees and -40 degrees in left hemispace 85% of the time. A comparison between free- and assigned-limb reaching kinematics revealed that free limb selection when reaching to the farthest positions was constrained by joint amplitude requirements and the time devoted to limb deceleration. Differences between free- and assigned-arm reaches were not evident when reaching to the midline and positions of +/-10 degrees , even though the right arm was freely selected most often for these positions. Different factors contribute to limb selection as a function of distance into a specific hemispace. PMID- 21978265 TI - Vascular endothelial growth factor and interleukin-6 are correlated with serous retinal detachment in central retinal vein occlusion. AB - PURPOSE/AIM: To investigate aqueous humour and vitreous fluid levels of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) in patients with central retinal vein occlusion (CRVO) and serous retinal detachment. MATERIALS AND METHODS: In twenty patients (20 eyes) with CRVO and 8 patients (8 eyes) with non-ischaemic ocular disease as controls, optical coherence tomography showed that 10 CRVO patients had serous retinal detachment (subretinal fluid with low reflectivity) and 10 patients had cystoid macular oedema (hyporeflective intraretinal cavities). Retinal ischaemia was evaluated from the area of capillary nonperfusion on fluorescein angiograms. To measure VEGF and IL-6 levels, aqueous humour and vitreous fluid samples were obtained during combined pars plana vitrectomy and cataract surgery. RESULTS: Ischaemia was significantly more frequent among the CRVO patients with serous retinal detachment than those with cystoid macular oedema (10/10 vs. 3/10, P = 0.001). Aqueous humour levels of VEGF and IL-6 were significantly higher in the serous patients than the cystoid patients (P = 0.004 and P < 0.001, respectively). Vitreous fluid levels of VEGF and IL-6 were also significantly higher in the serous patients than the cystoid patients (P = 0.007 and P < 0.001, respectively). CONCLUSIONS: These results suggest that a marked increase of vascular permeability due to upregulation of VEGF and IL-6 may contribute to serous retinal detachment in patients with CRVO. PMID- 21978263 TI - DC-STAMP knock-down deregulates cytokine production and T-cell stimulatory capacity of LPS-matured dendritic cells. AB - BACKGROUND: Dendritic cells (DCs) are the highly specialized antigen presenting cells of the immune system that play a key role in regulating immune responses. DCs can efficiently initiate immune responses or induce tolerance. Due to this dual function, DCs are studied in the context of immunotherapy for both cancer and autoimmune diseases. Characterization of DC-specific genes, leading to better understanding of DC immunobiology, will help to guide their use in clinical settings. We previously identified DC-STAMP, a multi-membrane spanning protein preferentially expressed by DCs. DC-STAMP resides in the endoplasmic reticulum (ER) of immature DCs and translocates towards the Golgi compartment upon maturation. In this study we knocked down DC-STAMP in mouse bone marrow-derived DCs (mBMDCs) to determine its function. RESULTS: We demonstrate that DC-STAMP knock-down mBMDCs secrete less IL-6, IL-12, TNF-alpha and IL-10 while IL-1 production is enhanced. Moreover, LPS-matured DC-STAMP knock-down mBMDCs show impaired T cell activation potential and induction of Th1 responses in an alloreaction. CONCLUSIONS: We show that DC-STAMP plays an important role in cytokine production by mBMDCs following LPS exposure. Our results reveal a novel function of DC-STAMP in regulating DC-initiated immune responses. PMID- 21978266 TI - Disentangling the roles of frequency-vs. state-dependence in generating individual differences in behavioural plasticity. AB - Theoretical work suggests that both negative frequency-dependent payoffs and state-dependent payoffs can lead to individual variation in behavioural plasticity. We investigated the roles of both frequency- and state-dependence on the occurrence of individual variation in behavioural plasticity in a series of experiments where we manipulated perceived predation danger for red knots (Calidris canutus islandica). We found individual variation in plasticity in a trait with negative frequency-dependent payoffs (vigilance), but not in a trait with positive frequency-dependent payoffs (escape flights). Furthermore, there was no correlation between the average level of vigilance under low predation danger and the magnitude of response to increased predation danger, as would be expected under state-dependence. Thus, our results provide support for the hypothesis that negative-frequency dependence favours individual variation in plasticity. However, negative-frequency dependence alone cannot explain why plasticity would be consistent within individuals, and future studies should address the factors that might favour individual consistency. PMID- 21978272 TI - Light-emitting conjugated polymers with microporous network architecture: interweaving scaffold promotes electronic conjugation, facilitates exciton migration, and improves luminescence. AB - Herein we report a strategy for the design of highly luminescent conjugated polymers by restricting rotation of the polymer building blocks through a microporous network architecture. We demonstrate this concept using tetraphenylethene (TPE) as a building block to construct a light-emitting conjugated microporous polymer. The interlocked network successfully restricted the rotation of the phenyl units, which are the major cause of fluorescence deactivation in TPE, thus providing intrinsic luminescence activity for the polymers. We show positive "CMP effects" that the network promotes pi conjugation, facilitates exciton migration, and improves luminescence activity. Although the monomer and linear polymer analogue in solvents are nonemissive, the network polymers are highly luminescent in various solvents and the solid state. Because emission losses due to rotation are ubiquitous among small chromophores, this strategy can be generalized for the de novo design of light-emitting materials by integrating the chromophores into an interlocked network architecture. PMID- 21978273 TI - Direct mapping of morphological distribution of syringyl and guaiacyl lignin in the xylem of maple by time-of-flight secondary ion mass spectrometry. AB - Lignin, one of the main structural polymer of plant cell walls, varies in amount and monomeric composition among tissue and cell types, as well as among plant species. However, few analytical methods are available that can conveniently and accurately determine the morphological distribution of lignin units at the cellular level. In this report, we used time-of-flight secondary ion mass spectrometry (TOF-SIMS) to directly map guaiacyl (G) and syringyl (S) lignin units in several successive growth rings of the maple xylem. TOF-SIMS imaging and a semiquantitative approach revealed clear difference in the annual distribution of lignins between the fiber and vessel. While the vessel walls were constantly G rich with varied S/G ratios through a growth ring, the fibers showed fairly regular annual distribution of lignins in which the earlywood was S-rich with an almost constant S/G ratio and the latewood was G-rich resulting from a decrease of the S unit. The reliability of TOF-SIMS results was demonstrated by its high correlation with the results of thioacidolysis on radial distribution of the S/G ratio in several contiguous tree rings and also in the latewood and earlywood of each ring. These results indicate that TOF-SIMS allows direct visualization of lignin composition in plant tissues. PMID- 21978267 TI - Estimated dietary phytoestrogen intake and major food sources among women during the year before pregnancy. AB - BACKGROUND: Phytoestrogens may be associated with a variety of different health outcomes, including outcomes related to reproductive health. Recently published data on phytoestrogen content of a wide range of foods provide an opportunity to improve estimation of dietary phytoestrogen intake. METHODS: Using the recently published data, we estimated intake among a representative sample of 6,584 women of reproductive age from a multi-site, population-based case-control study, the National Birth Defects Prevention Study (NBDPS). The NBDPS uses a shortened version of the Willett food frequency questionnaire to estimate dietary intake during the year before pregnancy. We estimated intake among NBDPS control mothers. RESULTS: Lignans contributed 65% of total phytoestrogen intake; isoflavones, 29%; and coumestrol, 5%. Top contributors to total phytoestrogen intake were vegetables (31%) and fruit (29%); for isoflavones, dairy (33%) and fruit (21%); for lignans, vegetables (40%) and fruit (29%); and for coumestans, fruit (55%) and dairy (18%). Hispanic women had higher phytoestrogen intake than non-Hispanic white or black women. Associations with maternal age and folic acid containing supplements were more modest but indicated that older mothers and mothers taking supplements had higher intake. CONCLUSIONS: The advantage of the approach used for the current analysis lies in its utilization of phytoestrogen values derived from a single laboratory that used state-of-the-art measurement techniques. The database we developed can be applied directly to other studies using food frequency questionnaires, especially the Willett questionnaire. The database, combined with consistent dietary intake assessment, provides an opportunity to improve our ability to understand potential associations of phytoestrogen intake with health outcomes. PMID- 21978274 TI - Immediate laparoscopic repair of a traumatic abdominal wall hernia in a 2-year old child. AB - Traumatic abdominal wall hernia in children with intact skin is rare. This type of hernia is caused by blunt trauma abdomen that does not penetrate the skin. These hernias have been repaired in adults by open repair. We report the first laparoscopic repair of this condition in a 2-year-old child with blunt abdominal trauma in emergent settings. PMID- 21978275 TI - Trocar-site hernia after single-port cholecystectomy: not an exceptional complication? AB - BACKGROUND: When compared with standard multiport laparoscopy, the larger fascial incision in single-port surgery (SPS) may imply a potentially increased risk of surgical-site complications, such as herniation. The long-term risk of access site complications in SPS is still unpredictable. METHODS: Between July 2009 and May 2011, n=78 patients (n=54 females), with a median age of 42 years (range: 18 85 years), underwent single-port cholecystectomy. The median body mass index was 25.4 kg/m(2) (range: 17-39 kg/m(2)). All surgeries were performed by a single surgeon (K.K.) using a completely reusable single-port access device (X-ConeTM; KARL STORZ GmbH, Tuttlingen, Germany), and fascial closure technique was comparable in all patients. The first 50 patients (n=32 females) attended a structured follow-up examination including a meticulous clinical examination and ultrasonography of the access site at a median follow-up time of 17 months (range: 9-23 months). RESULTS: We recorded postoperative complications in 5 of the 50 patients (10%) after single-port cholecystectomy. Four occurred in the early postoperative course and presented as mild wound complications. One of the 50 patients (2%) experienced a symptomatic trocar-site hernia (TSH) 4 months after surgery. No biliary complications (bile leakage, retained stones, etc.) were recorded. CONCLUSIONS: Although potentially biased by a relatively small number of patients, our study provides evidence that TSH after single-port cholecystectomy is (i) not less frequent when compared with standard laparoscopy, (ii) not as infrequent as suggested by the current literature, and (iii) not only associated with technical failure or patients' comorbidity. PMID- 21978276 TI - Methodology for setting risk-based concentrations of contaminants in soil and groundwater and application to a model contaminated site. AB - In Japan, environmental standards for contaminants in groundwater and in leachate from soil are set with the assumption that they are used for drinking water over a human lifetime. Where there is neither a well nor groundwater used for drinking, the standard is thus too severe. Therefore, remediation based on these standards incurs excessive effort and cost. In contrast, the environmental assessment procedure used in the United States and the Netherlands considers the site conditions (land use, existing wells, etc.); however, a risk assessment is required for each site. Therefore, this study proposes a new framework for judging contamination in Japan by considering the merits of the environmental standards used and a method for risk assessment. The framework involves setting risk-based concentrations that are attainable remediation goals for contaminants in soil and groundwater. The framework was then applied to a model contaminated site for risk management, and the results are discussed regarding the effectiveness and applicability of the new methodology. PMID- 21978277 TI - Specific interactions of sodium salts with alanine dipeptide and tetrapeptide in water: insights from molecular dynamics. AB - We examine computationally the dipeptide and tetrapeptide of alanine in pure water and solutions of sodium chloride (NaCl) and iodide (NaI), with salt concentrations up to 3 M. Enhanced sampling of the configuration space is achieved by the replica exchange method. In agreement with other works, we observe preferential sodium interactions with the peptide carbonyl groups, which are enhanced in the NaI solutions due to the increased affinity of the less hydrophilic iodide anion for the peptide methyl side-chains and terminal blocking groups. These interactions have been associated with a decrease in the helicities of more complex peptides. In our simulations, both salts have a small effect on the dipeptide, but consistently stabilize the intramolecular hydrogen-bonding interactions and "alpha-helical" conformations of the tetrapeptide. This behavior, and an analysis of the intermolecular interaction energies show that ion-peptide interactions, or changes in the peptide hydration due to salts, are not sufficient determining factors of the peptide conformational preferences. Additional simulations suggest that the observed stabilizing effect is not due to the employed force-field, and that it is maintained in short peptides but is reversed in longer peptides. Thus, the peptide conformational preferences are determined by an interplay of energetic and entropic factors, arising from the peptide sequence and length and the composition of the solution. PMID- 21978278 TI - Prevalence and consequences of musculoskeletal symptoms in symphony orchestra musicians vary by gender: a cross-sectional study. AB - BACKGROUND: Musculoskeletal symptoms are common in the neck, back, and upper limbs amongst musicians. Playing-related musculoskeletal disorders have been found to range from 32% to 87% with a tendency for female musicians to have more problems than males. Studies of musculoskeletal problems in instrumentalists have generally involved pre-professional musicians or populations comprising musicians of different levels. The objective of this study was therefore to investigate the prevalence, duration and consequences of musculoskeletal symptoms in professional symphony orchestra musicians. METHODS: A cross-sectional questionnaire study. The study population comprised of 441 musicians from six Danish symphony orchestras; 342 (78%) completed the questionnaire. RESULTS: During the last year 97% of the women and 83% of the men experienced symptoms in at least one of nine anatomic regions (neck, upper and lower back, shoulders, elbows, and hands and wrists). 86% of the women and 67% of the men experienced symptoms for more than seven days, while 63% of the women and 49% of the men had symptoms for more than 30 days. Woodwind players had a lower risk for musculoskeletal symptoms and a lower risk for the consequences. Among consequences were changed way of playing, reported by 73% of the musicians, difficulty in daily activities at home, reported by 55%, and difficulty in sleeping, reported by 49%. Their health behaviour included taking paracetamol as the most used analgesic, while physiotherapists and general practitioners were reported as the most consulted health care professionals concerning musculoskeletal problems.Results regarding symptoms in six anatomic regions were compared to results for a sample of the general Danish workforce. Symptoms were more frequent in musicians and lasted longer than in the general workforce. This applied to both genders. CONCLUSIONS: Within the last year most symphony orchestra musicians experienced musculoskeletal symptoms in the neck, back or upper extremities. The symptoms impacted on their level of function in and outside work and were reflected in their health behaviour. Generally women had a higher risk than men and woodwind players a lower risk than other instrumentalists. Finally, symptoms were more frequent and lasted longer in the musicians than in the general workforce. PMID- 21978279 TI - Expression of pERK and pAKT in pediatric high grade astrocytomas: correlation with YKL40 and prognostic significance. AB - The Ras signaling pathway, consisting of mitogen-activated protein kinase (MAPK) and PI3K/AKT signaling, is a prominent oncogenic pathways in adult diffuse gliomas, but few studies have evaluated such pathways in pediatric malignant gliomas. We investigated by immunohistochemistry MAPK and AKT signaling in a series of 28 pediatric high-grade gliomas (WHO grade III and IV). We sought a possible association of phospho-ERK (p-ERK) and phospho-AKT (p-AKT) with expression of other proteins involved in the Ras pathway, that is, YKL40, epidermal growth factor receptor (EGFR), EGFR vIII and c-Met. Moreover we correlated the expression of p-ERK and p-AKT with prognosis. No cases showed expression for c-Met and EGFR, and only one case was positive for EGFR vIII. YKL 40 protein was expressed in 43% of cases. We detected expression of p-ERK and p AKT in 61% and 57%, respectively, of pediatric high grade gliomas. Statistical analysis comparing the two groups in term of high and low p-ERK and p-AKT expression showed a trend toward worse overall survival in patients with high expression of p-AKT. The activation of ERK and AKT suggest a possible role of this protein in inducing activation of the Ras signaling pathway in pediatric high-grade gliomas. Moreover high levels of p-AKT are associated with worse overall survival. PMID- 21978280 TI - Type 2 diabetes, metformin and lactic acidosis-defining the risk and promoting safe practice. PMID- 21978282 TI - Improved antioxidant activity of BKOS Thai jasmine rice. AB - Thai jasmine rice (Oryza sativa L. cv. KDML105) is highly valued due to its subtle aroma, robust seed characteristics and high nutritional quality. Low energy ion-beam bombardment was chosen to improve the quality of jasmine rice by mutation induction. One mutated variety, named BKOS, was found to exhibit a deep purple colour due to an increased accumulation of anthocyanin. The total phenolic content and antioxidant activities of cooked and uncooked rice extracts were compared with KDML105, BKOS and other rice mutants created by a low-energy ion beam. The BKOS extracts showed the highest total phenol content (0.140 and 0.096 mg of gallic acid equivalent (GAE) g(-1) dry extract from uncooked and cooked rice, respectively). The BKOS extracts also had improved antioxidant activities, determined using three standard methods: 2,2'-diphenyl-1-picrylhdrazyl (DPPH) free radical scavenging, ABTS radical cation (ABTS*(+)) decolourisation and ferric-reducing antioxidant power assays. BKOS extracts showed 2-2.5-fold increased levels for each method. Interestingly, there was no significant difference between the antioxidant activities of the cooked and uncooked BKOS rice extracts. The increased quantity of antioxidants in this anthocyanin-based natural product could allow antioxidants to be consumed by a wider population than what is currently possible. PMID- 21978281 TI - Calcium ions to cross-link supramolecular nanofibers to tune the elasticity of hydrogels over orders of magnitude. AB - Learning from the stabilization of protein structures, we combine aromatic aromatic and electrostatic interactions to tailor the elasticity of supramolecular hydrogels. Specifically, calcium ions allow interfiber cross-links among the supramolecular nanofibers of small peptides that consist of multiple carboxylic acid and aromatic groups. A small change in the concentration of calcium increases the elasticity of hydrogels over several orders of magnitude. This simple approach not only demonstrates a biomimetic design of materials but also confirms that the combination of multiple aromatic-aromatic interactions and multiple calcium salt bridges is a feasible way to control the mechanical properties of soft nanomaterials. PMID- 21978283 TI - Evolution of amide stacking in larger gamma-peptides: triamide H-bonded cycles. AB - The single-conformation spectroscopy of two model gamma-peptides has been studied under jet-cooled conditions in the gas phase. The methyl-capped triamides, Ac gamma(2)-hPhe-gamma(2)-hAla-NHMe and Ac-gamma(2)-hAla-gamma(2)-hPhe-NHMe, were probed by resonant two-photon ionization (R2PI) and resonant ion-dip infrared (RIDIR) spectroscopies. Four conformers of Ac-gamma(2)-hPhe-gamma(2)-hAla-NHMe and three of Ac-gamma(2)-hAla-gamma(2)-hPhe-NHMe were observed and spectroscopically interrogated. On the basis of comparison with the predictions of density functional theory calculations employing a dispersion-corrected functional (omegaB97X-D/6-311++G(d,p)), all seven conformers have been assigned to particular conformational families. The preference for formation of nine membered rings (C9) observed in a previous study [James, W. H., III et al., J. Am. Chem. Soc. 2009, 131, 14243] of the smaller analog, Ac-gamma(2)-hPhe-NHMe, carries over to these triamides, with four of the seven conformers forming C9/C9 sequential double-ring structures, and one conformer a C9/C14 bifurcated double ring. The remaining two conformers form C7/C7/C14 H-bonded cycles involving all three amide NH groups, unprecedented in other peptides and peptidomimetics. The amide groups in these structures form a H-bonded triangle with the two trimethylene bridges forming loops above and below the molecule's midsection. The structure is a natural extension of amide stacking, with the two terminal amides blocked from forming the amide tristack by formation of the C14 H-bond. Pair interaction energy decomposition analysis based on the fragment molecular orbital method (FMO-PIEDA) is used to determine the nonbonded contributions to the stabilization of these conformers. Natural bond orbital (NBO) analysis identifies amide stacking with a pair of n -> pi* interactions between the nitrogen lone pairs and pi* orbitals on the carbonyl of the opposing amide groups. PMID- 21978284 TI - Superpotent [Dmt1] dermorphin tetrapeptides containing the 4-aminotetrahydro-2 benzazepin-3-one scaffold with mixed MU/delta opioid receptor agonistic properties. AB - Novel dermorphin tetrapeptides are described in which Tyr(1) is replaced by Dmt(1), where d-Ala(2) and Gly(4) are N-methylated, and where Phe(3)-Gly(4) residue is substituted by the constrained Aba(3)-Gly(4) peptidomimetic. Most of these peptidic ligands displayed binding affinities in the nanomolar range for both MU- and delta-opioid receptors but no detectable affinity for the kappa opioid receptor. Measurements of cAMP accumulation, phosphorylation of extracellular signal-regulated kinase (ERK1/2) in HEK293 cells stably expressing each of these receptors individually, and functional screening in primary neuronal cultures confirmed the potent agonistic properties of these peptides. The most potent ligand H-Dmt-NMe-d-Ala-Aba-Gly-NH(2) (BVD03) displayed mixed MU/delta opioid agonist properties with picomolar functional potencies. Functional electrophysiological in vitro assays using primary cortical and spinal cord networks showed that this analogue possessed electrophysiological similarity toward gabapentin and sufentanil, which makes it an interesting candidate for further study as an analgesic for neuropathic pain. PMID- 21978285 TI - Ex vivo calcium percutaneous eggression in normal and tape-stripped human skin. AB - Ions play a crucial role in skin homeostasis. Calcium, a participant in wound healing and keratinization, is localized at an increasing gradient from the stratum basal to the stratum granulosum. In vivo and in vitro studies show disturbances in this gradient in damaged skin. We developed here a model to study ex vivo calcium outward flux from normal and tape-stripped human skin. We measured here, with a calcium specific electrode, ex vivo calcium percutaneous eggression from dermis to epidermis in normal and tape-stripped skin places in franz cells, with a calcium source or not in the dermis compartment. Tape stripped skin released a greater calcium concentration and had a higher rate over time than normal skin in both cases. The rate went from 8.1.10(-3) +/- 8.9.10(-3) nmol.cm(-2).min(-1) to 4.8.10(-2) +/- 1.8.10(-2) nmol.cm(-2).min(-1) with no calcium in the dermis compartment and from 1.7.10(-1) +/- 1.2.10(-1) nmol.cm( 2).min(-1) to 5.9 +/- 3.4 nmol.cm(-2).min(-1) with calcium. Also calcium uptake from the dermis is greater in tape-stripped skin during the first 5 h of the experiment. This ex vivo method reproduced the increased of calcium skin permeability with a disrupted barrier. This approach aims to develop a non invasive method to measure calcium flux concentration in normal and damaged skin that might be reproduced and validated in vivo. PMID- 21978286 TI - Novel star HPMA-based polymer conjugates for passive targeting to solid tumors. AB - Novel star polymer-doxorubicin conjugates designed for passive tumor targeting have been developed and their potential for treatment of cancer has been investigated. In the present study the synthesis, physico-chemical characterization, drug release, bio-distribution and preliminary data of in vivo efficacy of the conjugates are described. In the water-soluble conjugates the core of a molecule formed by poly(amido amine) (PAMAM) dendrimers was grafted with semitelechelic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers bearing doxorubicin (Dox) attached by hydrazone bonds enabling intracellular pH controlled hydrolytic drug release, or by GFLG sequence susceptible to enzymatic degradation. The controlled synthesis utilizing semitelechelic copolymer precursors facilitated preparation of polymer conjugates in a broad range of molecular weights (1.1-3.0.10(5) g/mol). In contrast to free drug or linear conjugates the star polymer-Dox conjugates exhibited prolonged blood circulation and enhanced tumor accumulation in tumor-bearing mice indicating important role of the EPR effect. The star polymer-Dox conjugates showed significantly higher anti-tumor activity in vivo than Dox?HCl or its linear or graft polymer conjugates, if treated with a single dose 15 or 5 mg Dox eq./kg. Method of tumor initialization (acute or chronic experimental tumor models) significantly influenced effectiveness of the treatment with much lower success in treatment of mice bearing chronic tumors. PMID- 21978287 TI - Vitamin D levels and markers of arterial dysfunction in HIV. AB - HIV-infected patients have low vitamin D levels as well as an increase in cardiovascular (CVD) risk. We examined the relationship between vitamin D and three markers of arterial dysfunction among HIV-infected individuals on stable antiretroviral (ARV) therapy. Levels of 25-hydroxyvitamin D [25(OH)D] were assessed by chemiluminescent immunoassay (DiaSorin) in 100 enrollees into the Hawaii Aging with HIV-Cardiovascular Cohort Study, a cohort of HIV-infected subjects age >= 40 years on stable (>= 6 months) ARV therapy. The relationships between 25(OH)D levels and brachial artery flow-mediated dilation (FMD), right common carotid artery intima-media thickness (cIMT), and coronary artery calcium (CAC) were examined. Analytical methods included Pearson's correlations, Kruskal Wallis tests, relative risks, and linear regression models. The cohort was 86% male and 60% white with a median age of 52 years and CD4 of 510 cells/mm(3). The median (Q1, Q3) level of 25(OH)D was 27.9 ng/ml (21.8, 38.3). There were 72 FMD, 50 cIMT, and 90 CAC measurements available for analyses. A significant correlation was observed between 25(OH)D levels and FMD (r=0.30, p=0.01) but not with cIMT (r=-0.05, p=0.76). In a linear regression model, Framingham risk score attenuated the relationship between FMD and 25(OH)D. Those with lower 25(OH)D levels were at slightly higher risk of having CAC (RR=1.02, p=0.04). Among those with CAC, lower 25(OH)D levels were not associated with higher CAC scores (p=0.36). Lower vitamin D levels are associated with evidence of subclinical arterial dysfunction in HIV-infected individuals. The significance of these findings warrants further investigation. PMID- 21978288 TI - Effects of receptor modification and temperature on dynamics of sensory complexes in Escherichia coli chemotaxis. AB - BACKGROUND: Extracellular stimuli in chemotaxis of Escherichia coli and other bacteria are processed by large clusters of sensory complexes. The stable core of these clusters is formed by transmembrane receptors, a kinase CheA, and an adaptor CheW, whereas adaptation enzymes CheR and CheB dynamically associate with the clusters via interactions with receptors and/or CheA. Several biochemical studies have indicated the dependence of the sensory complex stability on the adaptive modification state of receptors and/or on temperature, which may potentially allow environment-dependent tuning of its signalling properties. However, the extent of such regulation in vivo and its significance for chemotaxis remained unclear. RESULTS: Here we used fluorescence recovery after photobleaching (FRAP) to confirm in vivo that the exchange of CheA and CheW shows a modest dependency on the level of receptor modification/activity. An even more dramatic effect was observed for the exchange kinetics of CheR and CheB, indicating that their association with clusters may depend on the ability to bind substrate sites on receptors and on the regulatory phosphorylation of CheB. In contrast, environmental temperature did not have a discernible effect on stability of the cluster core. Strain-specific loss of E. coli chemotaxis at high temperature could instead be explained by a heat-induced reduction in the chemotaxis protein levels. Nevertheless, high basal levels of chemotaxis and flagellar proteins in common wild type strains MG1655 and W3110 enabled these strains to maintain their chemotactic ability up to 42 degrees C. CONCLUSIONS: Our results confirmed that clusters formed by less modified receptors are more dynamic, which can explain the previously observed adjustment of the chemotaxis response sensitivity according to the level of background stimulation. We further propose that the dependency of CheR exchange on the availability of unmethylated sites on receptors is important to improve the overall chemotaxis efficiency by suppressing molecular noise under conditions of high ligand concentrations. Moreover, the observed stability of the cluster core at high temperature is in line with the overall thermal robustness of the chemotaxis pathway and allows maintenance of chemotaxis up to 42 degrees C in the common wild type strains of E. coli. PMID- 21978289 TI - Adult protective services clients confirmed for self-neglect: characteristics and service use. AB - Self-neglect is a complex and inadequately understood phenomenon that accounts for the majority of Adult Protective Services cases. This retrospective, record based study of the characteristics of 210 older adults who were reported to Adult Protective Services and confirmed for self-neglect revealed that common health problems included nutritional frailty, arthritis, and incontinence. Comparisons based upon length of service showed differences in worker-rated social environment risk, client capacity, and activities of daily living performance. Comparisons of findings with those of other studies of self-neglect underscore the need for systematic research on this population. PMID- 21978290 TI - Conceptual model and map of financial exploitation of older adults. AB - This article describes the processes and outcomes of three-dimensional concept mapping to conceptualize financial exploitation of older adults. Statements were generated from a literature review and by local and national panels consisting of 16 experts in the field of financial exploitation. These statements were sorted and rated using Concept Systems software, which grouped the statements into clusters and depicted them as a map. Statements were grouped into six clusters, and ranked by the experts as follows in descending severity: (a) theft and scams, (b) financial victimization, (c) financial entitlement, (d) coercion, (e) signs of possible financial exploitation, and (f) money management difficulties. The hierarchical model can be used to identify elder financial exploitation and differentiate it from related but distinct areas of victimization. The severity hierarchy may be used to develop measures that will enable more precise screening for triage of clients into appropriate interventions. PMID- 21978291 TI - Abuse and neglect experienced by aging chinese in Canada. AB - The traditional values of Chinese culture promote care and respect toward older adults. While it appears to be ironic to discuss issues of abuse and neglect in the Chinese culture, research findings in Chinese societies do indicate the occurrences of such problems. However, little research on the abuse and neglect of older Chinese in Western societies has been available. This study aims to examine the incidence of abuse and neglect and the associated correlates based on data collected from a random sample of 2,272 aging Chinese 55 years and older in seven Canadian cities. The findings show that 4.5% of the participants reported experiencing at least one incident of maltreatment or neglect within the past year. The most common forms of neglect and abuse experienced by the aging Chinese include being scolded, yelled at, treated impolitely all the time, and ridiculed. Close family members such as spouses and sons are those that most commonly maltreat older Chinese. Those who were more likely to report at least one incident of maltreatment or neglect were older adults living with others; they tended to have no education, more access barriers, more chronic illnesses, less favorable mental health, and a higher level of identification with Chinese cultural values. The findings implied that the face value of respect and care received by older people in Chinese culture should not be taken for granted. Culturally appropriate precautionary steps are needed for prevention and early problem identification. PMID- 21978292 TI - Elder abuse research: a systematic review. AB - The purpose of this research was to provide a systematic review of, and assign an evidence grade to, the research articles on elder abuse. Sixteen health care and criminal justice literature databases were searched. Publications were reviewed by at least two independent readers who graded each from A (evidence of well designed meta-analysis) to D (evidence from expert opinion or multiple case reports) on the quality of the evidence gained from the research. Of 6,676 titles identified in the search, 1,700 publications met inclusion criteria; omitting duplicates, 590 publications were annotated and graded. PMID- 21978293 TI - Preventing and combating elder mistreatment in flanders (belgium): general overview. AB - In Flanders, the state that comprises the Dutch-speaking part of Belgium, the structural attention given to the problem of elder mistreatment has grown slowly throughout the last decade. Equivalent to the evolution in most other western countries, there is nevertheless still a great lack of scientific research, and several governments (federal, regional, supralocal, and local) are still very reluctant to provide sufficient means in order to prevent and combat elder mistreatment. This article aims to present a general overview of the current state of affairs in the regional state of Flanders to address elder mistreatment. More concretely, it will highlight the history of the Flemish Reporting Point for Elder Abuse, what its aims are, and what definition and typology of elder mistreatment it uses in its daily activities. Because of the importance of well conducted scientific research and excellent academic support in order for policymakers and social services to deal efficiently with elder mistreatment, the lack of scientific research in Flanders also will be briefly highlighted. PMID- 21978296 TI - NiCl2(PMe3)(2)-catalyzed borylation of aryl chlorides. AB - The cross-coupling of aryl chlorides and bis(pinacolato)diboron was achieved using NiCl(2)(PMe(3))(2) catalyst in the presence of metal 2,2,2 trifluoroethoxide. The catalyst smoothly provided the desired products regardless of a variety of functional groups and substituted positions. PMID- 21978295 TI - Androgen receptor CAG repeat polymorphism in males of six non-human primate species. AB - BACKGROUND: Androgen receptor [CAG](n) microsatellite has been linked to human diseases. METHODS: Six non-human primates were genotyped for the [CAG](n) microsatellite. RESULTS: Marmosets and macaques are monomorphic, while mangabeys, baboons, and chimpanzees are polymorphic. CONCLUSIONS: Non-human primates that are polymorphic for the microsatellite are candidate animal models for CAG related diseases. PMID- 21978297 TI - A novel genus of multicellular magnetotactic prokaryotes from the Yellow Sea. AB - Multicellular magnetotactic prokaryotes (MMPs) are a group of magnetotactic microorganisms composed of 10-40 Gram-negative cells. Currently, all the identified MMPs show a spherical morphology and synthesize mainly iron sulfide magnetosomes. In this study, we report a novel genus of MMPs with peculiar ellipsoidal morphology and iron oxide magnetosomes, which were discovered in intertidal sediment of the Yellow Sea in China. Optical and fluorescence microscopy revealed that this organism was ~10 * 8 um in size and composed of ~40 cells enveloped by an outer layer. Scanning electron microscopy showed that the cells were arranged in 4-6 interlaced circles. Bullet-shaped magnetite magnetosomes were organized in chains roughly parallel to the long axis of the ellipsoidal MMPs when analysed by transmission electron microscopy. These MMPs displayed special escape motility, i.e. swimming rapidly from the edge to the centre of the droplet and then slowly back to the edge. In addition, they exhibited negative phototaxis. Light microscopy observations showed that the ellipsoidal MMPs reproduced by division along the body long axis. Both analysis of 16S rRNA gene sequence and fluorescence in situ hybridization revealed the ellipsoidal MMPs as a new genus of the Deltaproteobacteria. In summary, this novel genus of MMPs exhibit unique morphology, peculiar division process and distinct phylogenetic affiliation compared with the other MMPs. PMID- 21978298 TI - Computational design of thermostabilizing D-amino acid substitutions. AB - Judicious incorporation of D-amino acids in engineered proteins confers many advantages such as preventing degradation by endogenous proteases and promoting novel structures and functions not accessible to homochiral polypeptides. Glycine to D-alanine substitutions at the carboxy termini can stabilize alpha-helices by reducing conformational entropy. Beyond alanine, we propose additional side chain effects on the degree of stabilization conferred by D-amino acid substitutions. A detailed, molecular understanding of backbone and side chain interactions is important for developing rational, broadly applicable strategies in using D-amino acids to increase protein thermostability. Insight from structural bioinformatics combined with computational protein design can successfully guide the selection of stabilizing D-amino acid mutations. Substituting a key glycine in the Trp-cage miniprotein with D-Gln dramatically stabilizes the fold without altering the protein backbone. Stabilities of individual substitutions can be understood in terms of the balance of intramolecular forces both at the alpha-helix C-terminus and throughout the protein. PMID- 21978299 TI - Tracking of eating patterns and overweight - a follow-up study of Norwegian schoolchildren from middle childhood to early adolescence. AB - BACKGROUND: The aim of this study was to describe eating patterns in early adolescence and to determine associations between eating patterns and overweight from middle childhood (4th grade, 9 to 10 years old) to early adolescence (7th grade, 12 to 13 years old). METHODS: Children were recruited from primary schools in Telemark County, Norway. Dietary data were obtained by parental report using a food frequency questionnaire. Height and weight were objectively measured, and overweight was defined using international standard cut-off points. Complete data were obtained for 924 4th grade and 691 7th children, and 427 children provided complete data at both time points. Principal component analysis was applied to identify eating patterns. We used multiple logistic regression to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for being overweight. RESULTS: The same four distinct eating patterns were identified at both time points. Correlation coefficients for the factor scores of corresponding eating patterns at baseline and follow up ranged from 0.44 to 0.60. In the follow-up sample, 345 children (80%) were still of normal weight, while 41 (10%) remained overweight. Children with high "dieting" pattern scores and low "varied Norwegian" pattern scores in the 7th grade had an increased risk of being overweight. Children with stable or increased "varied Norwegian" pattern scores had a lower risk of remaining overweight over time than children with decreased scores for this pattern; adjusted OR: 0.4 (95% CI: 0.2, 0.8). This pattern included foods and meals close to current dietary guidelines, including vegetables, fruit and unrefined cereal products. We did not observe an increased risk of overweight in children with high "unhealthy" eating pattern scores, termed "snacking" or "junk/convenient" in either cross-sectional or longitudinal analyses. CONCLUSIONS: Slight to moderate stability of eating patterns was observed. Children adhering to a "varied Norwegian" eating pattern were less likely to remain overweight than children with declining adherence to this pattern. Overweight children should be encouraged to eat regular main meals and retain a diverse diet that includes unrefined plant foods, water and fish, rather than fat- and sugar-reduced foods and drinks. PMID- 21978300 TI - Utilization survey of a rural creek fishery in central Alabama. AB - A one-year angler intercept survey was conducted on Choccolocco Creek, a rural, limited access tributary to the Coosa River in northeastern Alabama. The purpose of the survey was to collect data and information about the behaviors and fish consumption habits of the recreational anglers who fish there. Nine survey locations were included in the stratified sampling plan, and sampling occurred throughout daylight hours, on weekdays and weekends/holidays, during all four seasons of the year. Surveys were completed on a total of 101 survey days between June 28, 2008 and June 27, 2009.(6) Seventy-two anglers were observed fishing during the survey period, and 52 (72%) of those individuals agreed to participate in the survey. Based on the information collected by the survey clerks, the angler population fishes the Creek between 1 and 54 times per year, with an average frequency of seven trips per year. The average number of months fished was three months per year, with a range of one to nine months. Only 15% of the anglers who participated in the survey (eight individuals) had succeeded in catching fish by the end of their trips, and only four of those individuals (8%) had retained any of the fish they had caught for consumption. Reasons provided for not retaining fish were that they either only fished for sport, did not catch enough fish to eat, or the fish they caught were too small to keep. Because so few anglers used and harvested fish from the resource, fish consumption rates could not be determined with a high degree of confidence. However, from these limited data it was estimated that the three anglers for whom consumption rates could be estimated had annualized average daily fish consumption rates of 0.14, 0.44, and 7.9 grams per day (g/day). The majority of anglers traveled less than 10 miles to fish the Creek. It was estimated that a total population of 173 anglers use the Creek each year. The results of this survey indicated that Choccolocco Creek is a local fishery that is not heavily used by area residents. PMID- 21978307 TI - Ionic parachor and its application in acetic acid ionic liquid homologue 1-alkyl 3-methylimidazolium acetate {[C(n)mim][OAc](n = 2,3,4,5,6)}. AB - Five acetic acid ionic liquids (AcAILs) [C(n)mim][OAc](n = 2,3,4,5,6) (1-alkyl-3 methylimidazolium acetate) were prepared by the neutralization method and characterized by (1)HNMR spectroscopy and differential scanning calorimetry (DSC). The values of their density and surface tension were measured at 298.15 +/ 0.05 K. Since the AcAILs can strongly form hydrogen bonds with water, the small amounts of water are difficult to remove from the AcAILs by common methods. In order to eliminate the effect of the trace water, the standard addition method (SAM) was applied to these measurements. As a new concept, ionic parachor was put forward. [OAc](-) was seen as a reference ion, and its individual value of ionic parachor was determined in terms of two extrathermodynamic assumptions. Then, the values of ionic parachors of a number of anions, [NTf(2)](-), [Ala](-), [AlCl(4)](-), and [GaCl(4)](-), were obtained by using the value of the ionic parachor of the reference ion; the parachor and surface tension of the investigated ionic liquids in literature were estimated. In comparison, the estimated values correlate quite well with their matching experimental values. PMID- 21978301 TI - HSP70i is a critical component of the immune response leading to vitiligo. AB - HSP70i and other stress proteins have been used in anti-tumor vaccines. This begs the question whether HSP70i plays a unique role in immune activation. We vaccinated inducible HSP70i (Hsp70-1) knockout mice and wild-type animals with optimized TRP-1, a highly immunogenic melanosomal target molecule. We were unable to induce robust and lasting depigmentation in the Hsp70-1 knockout mice, and in vivo cytolytic assays revealed a lack of cytotoxic T-lymphocyte activity. Absence of T-cell infiltration to the skin and maintenance of hair follicle melanocytes were observed. By contrast, depigmentation proceeded without interruption in mice lacking a tissue-specific constitutive isoform of HSP70 (Hsp70-2) vaccinated with TRP-2. Next, we demonstrated that HSP70i was necessary and sufficient to accelerate depigmentation in vitiligo-prone Pmel-1 mice, accompanied by lasting phenotypic changes in dendritic cell subpopulations. In summary, these studies assign a unique function to HSP70i in vitiligo and identify HSP70i as a targetable entity for treatment. PMID- 21978308 TI - Commentary on Kuntsche et al. (2011): Mothers and bottles--the role of gender norms in shaping drinking. PMID- 21978309 TI - Commentary on Agrawal et al. (2011): Assessing the impact of changes to diagnostic criteria on the estimated prevalence of alcohol use disorders in general population surveys. PMID- 21978310 TI - Commentary on Genberg et al. (2011): the structural vulnerability imposed by hypersegregated US inner-city neighborhoods--a theoretical and practical challenge for substance abuse research. PMID- 21978311 TI - Commentary on Turner et al. (2011): Significant global scale-up of harm reduction interventions and pragmatic research approaches needed to prevent hepatitis C transmission. PMID- 21978312 TI - What do we know about unplanned quit attempts? Practically nothing or nothing practical? PMID- 21978314 TI - Commentary on Etter & Bullen (2011): could E-cigs become the ultimate nicotine maintenance device? PMID- 21978315 TI - Reversing the taxes approach for a win-win tobacco control policy. PMID- 21978316 TI - Equity considerations in the calculation of cost-effectiveness in substance use disorder populations. PMID- 21978317 TI - Epidemiological characteristics of cognitive impairment of multiple sclerosis patients in a Latin American country. AB - We assessed cognitive performance and physical disability in 111 multiple sclerosis (MS) patients and 222 healthy controls in a multicenter study in Argentina to obtain the prevalence of cognitive impairment (CI) in a population of MS outpatients in Argentina. MS patients presented significantly lower scores in all Brief Repeatable Battery of Neuropsychology (BRB-N) tests than did the control group. The prevalence of CI was 43.2%. This study allowed us to obtain actual figures on the number of MS patients with CI in a Latin American sample. This validation is a very useful tool for clinical practice and for research studies to assess cognition in MS. PMID- 21978318 TI - Overall and worst gleason scores are equally good predictors of prostate cancer progression. AB - BACKGROUND: Gleason scoring has experienced several modifications during the past decade. So far, only one study has compared the prognostic abilities of worst (WGS) and overall (OGS) modified Gleason scores after the ISUP 2005 conference. Prostatic needle biopsies are individually paraffin-embedded in 57% of European pathology laboratories, whereas the rest of laboratories embed multiple (2 - 6) biopsies per one paraffin-block. Differences in the processing method can have a far-reaching effect, because reporting of the Gleason score (GS) is different for individually embedded and pooled biopsies, and GS is one of the most important factors when selecting treatment for patients. METHODS: The study material consisted of needle biopsies from 236 prostate cancer patients that were endocrine-treated in 1999-2003. Biopsies from left side and right side were embedded separately. Haematoxylin-eosin-stained slides were scanned and analyzed on web-based virtual microscopy. Worst and overall Gleason scores were assessed according to the modified Gleason score schema after analyzing each biopsy separately. The compound Gleason scores (CGS) were obtained from the original pathology reports. Two different grade groupings were used: GS 6 or less vs. 7 vs. 8 or above; and GS 7(3 + 4) or less vs. 7(4 + 3) and 8 vs. 9-10. The prognostic ability of the three scoring methods to predict biochemical progression was compared with Kaplan-Meier survival analysis and univariate and multivariate Cox regression analyses. RESULTS: The median follow-up time of the patients was 64.5 months (range 0-118). The modified GS criteria led to upgrading of the Gleason sums compared to the original CGS from the pathology reports 1999 2003 (mean 7.0 for CGS, 7.5 for OGS, 7.6 for WGS). In 43 cases WGS was > OGS. In a univariate analysis the relative risks were 2.1 (95%-confidence interval 1.8 2.4) for CGS, 2.5 (2.1-2.8) for OGS, and 2.6 (2.2-2.9) for WGS. In a multivariate analysis, OGS was the only independent prognostic factor. CONCLUSIONS: All of the three Gleason scoring methods are strong predictors of biochemical recurrence. The use of modified Gleason scoring leads to upgrading of GS, but also improves the prognostic value of the scoring. No significant prognostic differences between OGS and WGS could be shown, which may relate to the apparent narrowing of the GS scale from 2-10 to 5-10 due to the recent modifications. PMID- 21978319 TI - Macroscopic observations of molecular recognition: discrimination of the substituted position on the naphthyl group by polyacrylamide gel modified with beta-cyclodextrin. AB - Macroscopic molecular recognition observations were realized using polyacrylamide based gels modified with alpha-cyclodextrin (alpha-CD), beta-cyclodextrin (beta CD), 1-naphthylmethyl (1Np), and 2-naphthylmethyl (2Np) moieties, which are denoted as alphaCD(x)-gel, betaCD(x)-gel, 1Np(y)-gel, and 2Np(y)-gel, where x and y indicate the mol % of CD and Np moieties, respectively. The alphaCD(5)-gel did not adhere to either the 1Np(5)-gel or 2Np(5)-gel, whereas the betaCD(5)-gel interacted with both to form alternating or checkered assemblies. Although the difference in the association constants of beta-CD for the model polymers was small, the betaCD(x)-gel successfully discriminated between 1Np(y)-gel and 2Np(y) gel at the appropriate x and y. PMID- 21978321 TI - Concordance between antioxidant activities in vitro and chemical components of Radix Astragali (Huangqi). AB - Five Radix Astragali (RA) extracts were prepared and their antioxidant activities were measured in vitro using ABTS [2, 2'-azino-bis(3-ethylbenzothiazoline-6 sulphonic acid diammonium salt)], DPPH . (1,1-diphenyl-2-picrylhydrazyl radical), reducing power, *O2- and *OH assays. Their chemical contents were then determined, including total phenolics, total flavonoids, total saponins and total sugars. The 1/IC50 values of the various antioxidant assays were used to evaluate the level of antioxidant activity of the RA extracts (plot showing 1/IC50 values vs. chemical contents), and the average R values (correlation coefficients) of total phenolics and total flavonoids were 0.762 and 0.638. In contrast, the average R values of the total saponins and total sugars were -0.0386 and -0.132, respectively. This large difference clearly demonstrates that the antioxidant effects of RA in vitro might be generally considered to be a result of the presence of phenolic compounds (including flavonoids) but not astragalosides and polysaccharides. PMID- 21978320 TI - Progressive nonfluent aphasia: a rare clinical subtype of FTLD-TDP in Japan. AB - Progressive nonfluent aphasia (PNFA) is a clinical subtype of frontotemporal lobar degeneration (FTLD). FTLD with tau accumulation (FTLD-tau) and FTLD with TDP-43 accumulation (FTLD-TDP) both cause PNFA. We reviewed clinical records of 29 FTLD-TDP cases in the brain archive of our institute and found only one case of PNFA. The patient was an 81-year-old male at death. There was no family history of dementia or aphasia. He presented with slow, labored and nonfluent speech at age 75. Behavioral abnormality and movement disorders were absent. MRI at age 76 demonstrated atrophy of the perisylvian regions, including the inferior frontal gyrus, insular gyrus and superior temporal gyrus. The atrophy was more severe in the left hemisphere than the right. On post mortem examinations, neuronal loss was evident in these regions as well as in the substantia nigra. There were abundant TDP-43-immunoreactive neuronal cytoplasmic inclusions and round or irregular-shaped structures in the affected cerebral cortices. A few dystrophic neurites and neuronal intranuclear inclusions were also seen. FTLD-TDP showing PNFA seems to be rare but does exist in Japan, similar to that in other countries. PMID- 21978322 TI - C-H...pi interactions in the CHBrF2...HCCH weakly bound dimer. AB - The microwave spectra of four isotopologues of the CHBrF(2)...HCCH weakly bound dimer have been measured in the 6-18 GHz region using chirped-pulse and Balle Flygare Fourier-transform microwave spectroscopy. Spectra of (13)CH(79)BrF(2) and (13)CH(81)BrF(2) monomers have also been measured, and spectroscopic constants are reported. Measurement of spectra for the (79)Br and (81)Br isotopologues of CHBrF(2) complexed with both (12)C(2)H(2) and (13)C(2)H(2) have allowed the determination of a structure with C(s) symmetry for this complex. CHBrF(2) interacts with the triple bond of acetylene via a C-H...pi contact (R(H...pi) = 2.670(8) A) with the Br atom lying in the ab plane, located 3.293(40) A from a hydrogen atom of the HCCH molecule. The structure of CHBrF(2)...HCCH has been compared with recently studied related acetylene complexes, including a comparison with (and further structural analysis of) the CHClF(2)...HCCH complex. PMID- 21978323 TI - Theoretical study of mechanism and selectivity of copper-catalyzed C-H bond amidation of indoles. AB - Density functional theory calculations are used to study the reaction mechanism and origins of C2 selectivity in a copper(I)-catalyzed amidation of indoles. It is shown that concerted metalation-deprotonation is not able to reproduce the observed regioselectivity. Instead, an unprecedented mechanism based on a four center reductive elimination is proposed to be responsible for the reaction outcome. This mechanism has a lower reaction barrier and is able to reproduce the experimentally observed selectivity. A possible alternative mechanism involving a Cu(II) species instead of Cu(III) is presented, but it is shown that higher energy barriers are associated with this mechanism. An important technical detail is that addition of dispersion effects to the B3LYP results is necessary to reproduce the observed selectivity, although not important for the overall mechanistic proposal. PMID- 21978324 TI - Cyclodepsipeptides, sesquiterpenoids, and other cytotoxic metabolites from the filamentous fungus Trichothecium sp. (MSX 51320). AB - Two new cyclodepsipeptides (1 and 2), two new sesquiterpenoids (3 and 4), and the known compounds guangomide A (5), roseotoxin S, and three simple trichothecenes were isolated from the cytotoxic organic extract of a terrestrial filamentous fungus, Trichothecium sp. The structures were determined using NMR spectroscopy and mass spectrometry. Absolute configurations of the cyclodepsipeptides were established by employing chiral HPLC, while the relative configurations of 3 and 4 were determined via NOESY data. The isolation of guangomide A was of particular interest, since it was reported previously from a marine-derived fungus. PMID- 21978325 TI - Do FRAX/NOGG guidelines predict fractures in post-menopausal women with Type 2 diabetes? PMID- 21978326 TI - Development of a pH-responsive imprinted polymer for diclofenac and study of its binding properties in organic and aqueous media. AB - Three different molecularly imprinted polymers (MIPs) for drug delivery of diclofenac in gastrointestinal tract were synthesized employing bulk polymerization method and their binding and release properties were studied in different pH values. Methacrylic acid (MAA), methacrylamide (MAAM) and 4-vinyl pyridine (4VP) were tested as functional monomers and ethylene glycole dimethacrylate (EDMA) was used as a cross-linker monomer in polymeric feed. Binding properties and imprinting factor (IF) of MIPs were studied in comparison with their non-imprinted ones (Blank) in organic and aqueous media. Diclofenac release in aqueous solvents at pH values of 1.5, 6.0 and 8.0, simulating gastrointestinal fluids, were also studied. The results indicated the specific binding of diclofenac to imprinted polymers. Duo to the stronger non-specific bounds in aqueous solutions, IF values decreased in water compared to acetonitrile as an organic medium. Our results proved that all polymers represented pH-responsive diclofenac delivery at above conditions. The data showed that imprinted polymer, prepared by MAA had superior properties, in comparison with other polymers, for minimum release (14%) of drug in gastric acid and maximum release (90%) in basic condition. The results indicated that diclofenac imprinted polymer could be used as a pH-responsive matrix in preparation of a new drug delivery system for diclofenac. PMID- 21978327 TI - Low molecular weight heparins in the treatment of lung cancer. AB - INTRODUCTION: Lung cancer is the major cause of cancer-related death. Venous thromboembolic events (VTEs) occur frequently in lung cancer and are a poor prognostic marker. For prevention and treatment of VTE, low molecular weight heparins (LMWH) are superior to vitamin K antagonists. There is some evidence that LMWH may improve survival in cancer patients. AREAS COVERED: The areas covered in this review are: lung cancer and VTEs; role of LMWH in treatment of VTEs; anticancer mechanism of heparins and clinical trials with LMWH in lung cancer. EXPERT OPINION: LMWH plays an important role in prevention and treatment of VTEs in lung cancer. Although there is evidence from both preclinical data and retrospective analysis of clinical trials that LMWH may prolong survival this is not confirmed by prospective randomized clinical trials. Several clinical trials on this subject in lung cancer are ongoing and have to be awaited. PMID- 21978328 TI - Improved assessment needed for young doctors. PMID- 21978329 TI - Long-term outcomes for patients with cystic fibrosis in Australia. PMID- 21978330 TI - Why is disulfiram not on the PBS? PMID- 21978331 TI - The dangers of dogma in medicine. PMID- 21978332 TI - Obesity and chronic disease: have we missed the point? PMID- 21978333 TI - "I want to consume this product; should public health experts stop me?"--Yes- Opposing views. PMID- 21978334 TI - I want to consume this product, should public health experts stop me?"--No- Opposing views. PMID- 21978335 TI - New aspirations: the debate on aspiration pneumonia treatment guidelines. AB - Aspiration pneumonia occurs most commonly in patients with a predisposition to aspiration (eg, those with neurological bulbar dysfunction). There is limited evidence regarding the involvement of anaerobes in most cases of aspiration pneumonia. Most patients respond to treatment for aspiration pneumonia without specific anti-anaerobic therapy such as metronidazole. Metronidazole has adverse side effects, and widespread use where not indicated can promote carriage of multiresistant intestinal flora such as vancomycin-resistant enterococci. Use of metronidazole may be appropriate in patients with aspiration pneumonia and evidence of a lung abscess, necrotising pneumonia, putrid sputum or severe periodontal disease. PMID- 21978336 TI - The 2010 specialist trainees survey. PMID- 21978337 TI - Factors affecting outpatient non-attendance in an Australian children's hospital. PMID- 21978338 TI - Counting the cost: estimating the number of deaths among recently released prisoners in Australia. PMID- 21978339 TI - Routine screening for vitamin D deficiency in early pregnancy. PMID- 21978340 TI - Spontaneous chylothorax in a 2-year-old child. PMID- 21978341 TI - Interferon-alpha-related microscopic polyangiitis in a patient with chronic hepatitis C infection. PMID- 21978342 TI - Individual responsibility for reducing obesity: the unintended consequences of well intended messages. PMID- 21978343 TI - Pharmacogenetic screening of Indigenous Australians. PMID- 21978344 TI - Emergency department website not worth the wait. PMID- 21978345 TI - Painful numb hands. AB - Carpal tunnel syndrome, resulting from median nerve compression at the wrist, is a common and often disabling mononeuropathy. Risk factors include female sex, family history, repetitive hand use, obesity, pregnancy and a variety of medical comorbidities including diabetes mellitus, rheumatoid arthritis, and other connective tissue diseases. In many cases, an accurate diagnosis can be reached on the basis of clinical history and supportive examination findings alone. Neurophysiological investigations are essential for confirming the diagnosis, assessing severity and excluding more generalised neuropathies, as well as providing a baseline preoperative index of median nerve function. Wrist splinting and local corticosteroid injection are effective treatments in the short term, but long-term data are lacking. Surgical (endoscopic or open) carpal tunnel release is effective and nearly always required to enable a return to work for patients with occupationally induced carpal tunnel syndrome. PMID- 21978346 TI - Changes in cystic fibrosis mortality in Australia, 1979-2005. AB - OBJECTIVE: To assess mortality trends among people with cystic fibrosis (CF) in Australia. DESIGN AND SETTING: We augmented Australian summary data for deaths from CF registered during 1979-2005 with information from Australian transplant centres on lung transplantation among CF patients for 1989-2005 to allow us to follow trends in all "mortality events" (death or lung transplantation). MAIN OUTCOME MEASURE: Age at death or lung transplantation. RESULTS: Between 1979 and 2005, the mean age at death increased from 12.2 years to 27.9 years for males and from 14.8 years to 25.3 years for females. Overall, female deaths in childhood (0 14 years) occurred at an age-standardised rate of 0.40 per 100,000 (95% CI, 0.34 0.45) during 1979-2005, which exceeded the corresponding rate for males of 0.24 (95% CI, 0.20-0.28) per 100,000. Among 0-14-year-old boys, event rates declined markedly after 1989, but they declined later and more gradually for girls, with the result that the age-standardised rate for girls was 2.38 times that of boys during 1989-2005 (95% CI, 1.69-3.36). CONCLUSIONS: The pattern of CF mortality in Australia has changed substantially. Mortality rates continue to be higher for girls than for boys, but death in childhood has become uncommon. Survival has increased since 1979, but females continue to have reduced length of life. PMID- 21978347 TI - Cystic fibrosis in Australia, 2009: results from a data registry. AB - OBJECTIVES: To describe the demographics, clinical features and outcomes among people with cystic fibrosis (CF) in Australia and to estimate incidence of the disease. DESIGN AND SETTING: Cross-sectional analysis using data from the Australian Cystic Fibrosis Data Registry for 2009. MAIN OUTCOME MEASURES: Numbers of diagnoses, pulmonary and anthropometric measurements, microbiological culture results, rates of hospitalisation and transplantation, and numbers of medical complications and deaths. RESULTS: In 2009, data were submitted on 2986 people (48% female). Median age was 17.6 years and 49% of people were aged 18 years or over. Seventy-eight people were newly diagnosed. Fourteen people died and 14 people underwent lung transplantation in the year. Lung function and nutrition were relatively normal among children but deteriorated (more rapidly) among adolescents. With increasing age, progressive respiratory disease was apparent, and the frequency of CF-related complications and use of health care resources increased. In all age groups, there was a wide range in severity of lung disease and nutritional status. CONCLUSIONS: CF remains a progressive respiratory disease and is associated with multisystem complications. The acceleration in disease severity in adolescence and early adulthood suggests that better treatment at these stages is required to further improve survival. PMID- 21978348 TI - Portrayal of psychiatric genetics in Australian print news media, 1996-2009. AB - OBJECTIVE: To investigate how Australian print news media portray psychiatric genetics. DESIGN AND SETTING: Content and framing analysis of a structured sample of print news items about psychiatric genetics published in Australian newspapers between 1996 and 2009. MAIN OUTCOME MEASURES: Identify dominant discourses about aetiology of mental illness, and perceived clinical outcomes and implications of psychiatric genetics research. RESULTS: We analysed 406 eligible items about the genetics of psychiatric disorders. News coverage of psychiatric genetics has steadily increased since 1996. Items attributing the aetiology of psychiatric disorders to gene-environment interactions (51%) outnumbered items attributing only genetic (30%) or only environmental factors (20%). Of items that referred to heritability of mental illness, frames of genetic determinism (78%) occurred more frequently than probabilistic frames (22%). Of frames related to genetic prophesy, genetic optimism frames (78%) were used more frequently than frames of genetic pessimism (22%). Psychosocial and ethical implications of psychiatric genetics received comparatively relatively little coverage (23%). The analysis identified 22 predictions about psychiatric genetic discoveries and the availability of molecular-based interventions in psychiatry, most of which (20/22, 91%) failed to manifest by the predicted year. CONCLUSIONS: Excessive optimism about the power of genetic technology in psychiatric health care, perceived clinical benefits, and largely unfulfilled predictions about availability of these benefits could encourage unrealistic expectations about future molecular-based treatment options for mental health. PMID- 21978349 TI - Improving paediatric asthma outcomes in primary health care: a randomised controlled trial. AB - OBJECTIVE: To evaluate the effectiveness of the Practitioner Asthma Communication and Education (PACE) Australia program, an innovative communication and paediatric asthma management program for general practitioners. DESIGN: Randomised controlled trial. SETTING: General practices from two regions in metropolitan Sydney. PARTICIPANTS: 150 GPs, who were recruited between 2006 and 2008, and 221 children with asthma in their care. INTERVENTION: GPs in the intervention group participated in two 3-hour workshops, focusing on communication and education strategies to facilitate quality asthma care. MAIN OUTCOME MEASURES: Patient outcomes included receipt of a written asthma action plan (WAAP), appropriate medication use, parent days away from work, and child days away from school or child care. GP outcomes included frequency of providing a WAAP and patient education, communication and teaching behaviour, and adherence to national asthma guidelines regarding medication use. RESULTS: More patients of GPs in the intervention group reported receipt of a WAAP (difference, 15%; 95% CI, 2% to 28%; adjusted P=0.046). In the intervention group, children with infrequent intermittent asthma symptoms had lower use of inhaled corticosteroids (difference, 24%; 95% CI, -43% to -5%; P=0.03) and long-acting bronchodilators (difference, 19%; 95% CI, -34% to -5%; P=0.02). GPs in the intervention group were more confident when communicating with patients (difference 22%; 95% CI, 3% to 40%; P=0.03). A higher proportion of GPs in the intervention group reported providing a WAAP more than 70% of the time (difference, 23%; 95% CI, 11% to 36%; adjusted P=0.002) and prescribing spacer devices more than 90% of the time (difference, 29%; 95% CI, 16% to 42%; adjusted P=0.02). CONCLUSIONS: The PACE Australia program improved GPs' asthma management practices and led to improvements in some important patient outcomes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12607000067471. PMID- 21978350 TI - A review of prevocational medical trainee assessment in New South Wales. AB - OBJECTIVE: To evaluate the effectiveness of formal assessments of prevocational medical trainees (ie, interns, first-year residents and international medical graduates undergoing supervised training). DESIGN AND SETTING: Retrospective review of structured assessment forms that are completed by all prevocational trainees and their supervisors in New South Wales public hospitals. We reviewed the first 3390 assessment forms, representing assessments of 1072 trainees at 43 training sites (83% of all prevocational trainees in NSW) since January 2009. MAIN OUTCOME MEASURES: (i) Trainee ratings on 19 assessment items by self assessment and by supervisor assessment; and (ii) quantity and quality of written comments provided in assessments. RESULTS: At the end of term, 43% of trainees assessed themselves as performing "at expected level" on all 19 rating items. Nearly 99% of trainees were assessed by their supervisors as performing at or above the expected level on all assessment items. Written comments by supervisors were generally short and encouraging, but lacked specific feedback that trainees might use to guide improvements in performance. CONCLUSIONS: As currently used by trainees and supervisors, the assessment forms may underreport trainee underperformance, do not discriminate strongly between different levels of performance of trainees or the training system, and do not provide trainees with enough specific feedback to guide their professional development. PMID- 21978351 TI - A 17-year-old girl with severe respiratory failure and circulatory shock. PMID- 21978353 TI - Should efforts to minimise DNA contamination of forensic swabs be standardised across Australia? PMID- 21978354 TI - The Monte Carlo fallacy. PMID- 21978355 TI - Lambeth doctors. PMID- 21978357 TI - Short communication: lack of correlation between UGT1A1*6, *28 genotypes, and plasma raltegravir concentrations in Japanese HIV type 1-infected patients. AB - Raltegravir is metabolized by glucuronidation via UDP-glucuronosyltransferase 1A1 (UGT1A1). We analyzed the genotypes of UGT1A1 (*6, *27, and *28) and their contribution to plasma raltegravir concentrations in 56 Japanese HIV-1-infected patients in the National Hospital Organization Nagoya Medical Center of Japan. Among the 56 patients, the UGT1A1 genotype in two patients was *6 homozygote. Heterozygous variants were found in 13 patients for *6 and in 11 patients for *28, while all of the patients were found to carry wild-type sequences at the position corresponding to the *27 allele. Plasma raltegravir concentration of a male patient with *6 homozygote (0.53 MUg/ml) was modestly higher than that of patients with wild type (0.12 MUg/ml) or *6 heterozygote (0.16 MUg/ml). Another female patient with the *6 homozygote had a low plasma raltegravir concentration (0.03 MUg/ml). Patients heterozygous for the *6 or *28 allele did not display significantly different plasma raltegravir concentrations compared to patients homozygous for the respective wild-type allele. Thus, in the present study, we showed that heterozygous reduced-function *6 and *28 alleles appear to have no significant effect on plasma raltegravir concentrations in Japanese HIV-1 infected patients. However, variability in raltegravir concentration and small patient population precluded a correlation between UGT1A1*6 homozygosity and plasma raltegravir concentration. To clarify the contribution of UGT1A1*6 or *28 polymorphisms to plasma raltegravir concentrations, further investigations on larger subject populations are required. PMID- 21978358 TI - Transgenic mouse model for the formation of Hirano bodies. AB - BACKGROUND: Hirano bodies are actin-rich cytoplasmic inclusions found predominantly in the brain in association with a variety of conditions including aging and Alzheimer's disease. The function of Hirano bodies in normal aging and in progression of disease has not been extensively investigated due to a lack of experimental model systems. We have developed a transgenic mouse model by expression of a gain-of-function actin cross-linking protein mutant. RESULTS: We used the Cre/loxP system to permit tissue specific expression of Hirano bodies, and employed the murine Thy 1 promoter to drive expression of Cre recombinase in the brain. Hirano bodies were observed in the cerebral cortex and hippocampus of homozygous double transgenic 6 month old mice containing Cre. The Hirano bodies were eosinophilic rods, and also exhibited the paracrystalline F-actin filament organization that is characteristic of these inclusions. Mice with Hirano bodies appear healthy and fertile, but exhibited some alterations in both short-term and long-term synaptic plasticity, including paired-pulse depression rather than facilitation, and decreased magnitude of early LTP. CONCLUSIONS: Hirano bodies are not lethal and appear to have little or no effect on histology and tissue organization. Hirano bodies do modulate synaptic plasticity and exert clearly discernable effects on LTP and paired-pulse paradigms. This model system will allow us to investigate the impact of Hirano bodies in vivo, the pathways for formation and degradation of Hirano bodies, and whether Hirano bodies promote or modulate development of pathology and disease progression. PMID- 21978359 TI - Adjusting for sampling variability in sparse data: geostatistical approaches to disease mapping. AB - BACKGROUND: Disease maps of crude rates from routinely collected health data indexed at a small geographical resolution pose specific statistical problems due to the sparse nature of the data. Spatial smoothers allow areas to borrow strength from neighboring regions to produce a more stable estimate of the areal value. Geostatistical smoothers are able to quantify the uncertainty in smoothed rate estimates without a high computational burden. In this paper, we introduce a uniform model extension of Bayesian Maximum Entropy (UMBME) and compare its performance to that of Poisson kriging in measures of smoothing strength and estimation accuracy as applied to simulated data and the real data example of HIV infection in North Carolina. The aim is to produce more reliable maps of disease rates in small areas to improve identification of spatial trends at the local level. RESULTS: In all data environments, Poisson kriging exhibited greater smoothing strength than UMBME. With the simulated data where the true latent rate of infection was known, Poisson kriging resulted in greater estimation accuracy with data that displayed low spatial autocorrelation, while UMBME provided more accurate estimators with data that displayed higher spatial autocorrelation. With the HIV data, UMBME performed slightly better than Poisson kriging in cross validatory predictive checks, with both models performing better than the observed data model with no smoothing. CONCLUSIONS: Smoothing methods have different advantages depending upon both internal model assumptions that affect smoothing strength and external data environments, such as spatial correlation of the observed data. Further model comparisons in different data environments are required to provide public health practitioners with guidelines needed in choosing the most appropriate smoothing method for their particular health dataset. PMID- 21978360 TI - Simultaneous bulk- and surface-initiated controlled radical polymerization from planar substrates. AB - We employ Monte Carlo computer simulations to investigate the simultaneous controlled radical polymerization in solution and from a flat surface. The bulk polymers grow at faster rates and possess narrower molecular weight distribution than polymers initiated from flat, impenetrable surfaces. The rate of surface initiated polymerization depends on the density of initiator sites. Our results provide evidence that the assumption that the molecular weight of surface initiated polymers is equal to that of polymers grown in bulk, invoked often in determining the grafting density of surface-bound polymers, is generally invalid. PMID- 21978361 TI - A convergent strategy for the synthesis of polycyclic ethers by using oxiranyl anions. AB - A new [X+2+Y]-type for the convergent synthesis of polycyclic ethers based on an oxiranyl anion strategy was developed. The sequence involves nucleophilic substitution of a triflate with an oxiranyl anion followed by 6-endo cyclization, ring expansion, and reductive etherification. The protocol features a flexible approach toward trans-fused polycyclic arrays consisting of six- and seven membered ether rings from the same starting materials. PMID- 21978363 TI - The challenge of exposure correction for polar passive samplers--the PRC and the POCIS. PMID- 21978362 TI - The 'gating' residues Ile199 and Tyr326 in human monoamine oxidase B function in substrate and inhibitor recognition. AB - The major structural difference between human monoamine oxidases A (MAO A) and B (MAO B) is that MAO A has a monopartite substrate cavity of ~550 A(3) volume and MAO B contains a dipartite cavity structure with volumes of ~290 A(3) (entrance cavity) and ~400 A(3) (substrate cavity). Ile199 and Tyr326 side chains separate these two cavities in MAO B. To probe the function of these gating residues, Ile199Ala and Ile199Ala-Tyr326Ala mutant forms of MAO B were investigated. Structural data on the Ile199Ala MAO B mutant show no alterations in active site geometries compared with wild-type enzyme while the Ile199Ala-Tyr326Ala MAO B mutant exhibits alterations in residues 100-103 which are part of the loop gating the entrance to the active site. Both mutant enzymes exhibit catalytic properties with increased amine K(M) but unaltered k(cat) values. The altered K(M) values on mutation are attributed to the influence of the cavity structure in the binding and subsequent deprotonation of the amine substrate. Both mutant enzymes exhibit weaker binding affinities relative to wild-type enzyme for small reversible inhibitors. Ile199Ala MAO B exhibits an increase in binding affinity for reversible MAO B specific inhibitors which bridge both cavities. The Ile199Ala Tyr326Ala double mutant exhibits inhibitor binding properties more similar to those of MAO A than to MAO B. These results demonstrate that the bipartite cavity structure in MAO B plays an important role in substrate and inhibitor recognition to distinguish its specificities from those of MAO A and provide insights into specific reversible inhibitor design for these membrane-bound enzymes. PMID- 21978364 TI - Relative abundances of methane- and sulphur-oxidising symbionts in the gills of a cold seep mussel and link to their potential energy sources. AB - Bathymodiolus mussels are key species in many deep-sea chemosynthetic ecosystems. They often harbour two types of endosymbiotic bacteria in their gills, sulphur- and methane oxidisers. These bacteria take up sulphide and methane from the environment and provide energy to their hosts, supporting some of the most prolific ecosystems in the sea. In this study, we tested whether symbiont relative abundances in Bathymodiolus gills reflect variations in the highly spatially dynamic chemical environment of cold seep mussels. Samples of Bathymodiolus aff. boomerang were obtained from two cold seeps of the deep Gulf of Guinea, REGAB (5 degrees 47.86S, 9 degrees 42.69E, 3170 m depth) and DIAPIR (6 degrees 41.58S, 10 degrees 20.94E, 2700 m depth). Relative abundances of both symbiont types were measured by means of 3D fluorescence in situ hybridisation and image analysis and compared considering the local sulphide and methane concentrations and fluxes assessed via benthic chamber incubations. Specimens inhabiting areas with highest methane content displayed higher relative abundances of methane oxidisers. The bacterial abundances correlated also with carbon stable isotope signatures in the mussel tissue, suggesting a higher contribution of methane-derived carbon to the biomass of mussels harbouring higher densities of methane-oxidising symbionts. A dynamic adaptation of abundances of methanotrophs and thiotrophs in the gill could be a key factor optimising the energy yield for the symbiotic system and could explain the success of dual symbiotic mussels at many cold seeps and hydrothermal vents of the Atlantic and Gulf of Mexico. PMID- 21978365 TI - Foodborne exposure to pesticides and methylmercury in the United Arab Emirates. AB - As part of a comprehensive environmental health strategic planning project initiated by the government of Abu Dhabi, we assessed potential dietary exposure in the United Arab Emirates (UAE) to methylmercury (in seafood) and pesticides (in fruits and vegetables) above international guideline levels. We present results for the UAE population by age, gender, and body mass index. Our results show very low daily risks of exposure to pesticides in fruits and vegetables at levels exceeding WHO guidelines even under the conservative assumption that no pesticides are removed during washing and food preparation. Thus, exposure to pesticides on fruits and vegetables does not appear to be a major public health concern in the UAE. The chances of exposure to methylmercury in seafood are much higher; our model estimates a mean 1 in 5 daily risk of exceeding the FAO/WHO provisional tolerable weekly intake. However, great caution should be used in interpreting these results, as we analyzed only the risks and not the substantial benefits of fish consumption. In fact, previous studies have demonstrated that exposure to the n-3 polyunsaturated fatty acids in fish can increase IQ in developing children, and it can substantially decrease the risk in adults of coronary heart disease and stroke. Further research is warranted to compare the risk of Me-Hg exposure from fish to the nutritional benefits of fish consumption in the UAE and to determine appropriate methods to communicate risk and benefit information to the UAE population. PMID- 21978367 TI - A spoonful of sugar makes the melanoma go: the role of heparan sulfate proteoglycans in melanoma metastasis. AB - Heparan sulfate proteoglycans (HSPGs) have been shown to regulate signaling in many systems and are of increasing interest in cancer. While these are not the only sugars to drive melanoma metastasis, HSPGs play important roles in driving metastatic signaling cascades in melanoma. The ability of these proteins to modulate ligand-receptor interactions in melanoma has been quite understudied. Recent data from several groups indicate the importance of these ligands in modulating key signaling pathways including Wnt and fibroblast growth factor (FGF) signaling. In this review, we summarize the current knowledge regarding the structure and function of these proteoglycans and their role in melanoma. Understanding how HSPGs modulate signaling in melanoma could lead to new therapeutic approaches via the dampening or heightening of key signaling pathways. PMID- 21978366 TI - Perfluorinated compounds are related to breast cancer risk in Greenlandic Inuit: a case control study. AB - BACKGROUND: Breast cancer (BC) is the most common cancer for women in the western world. From very few cases an extraordinary increase in BC was observed in the Inuit population of Greenland and Canada although still lower than in western populations. Previous data suggest that exposure to persistent organic pollutants (POPs) might contribute to the risk of BC. Rat studies showed that perfluorinated compounds (PFCs) cause significantly increase in mammary fibroadenomas. This study aimed at evaluating the association between serum levels of POPs/PFCs in Greenlandic Inuit BC cases and their controls, and whether the combined POP related effect on nuclear hormone receptors affect BC risk. METHODS: Thirty-one BC cases and 115 controls were sampled during 2000-2003 from various Greenlandic districts. The serum levels of POPs, PFCs, some metals and the combined serum POP related effect on estrogen- (ER), androgen- (AR) and Ah-receptor (AhR) transactivity were determined. Independent student t-test was used to compare the differences and the odds ratios were estimated by unconditional logistic regression models. RESULTS: We observed for the very first time a significant association between serum PFC levels and the risk of BC. The BC cases also showed a significantly higher concentration of polychlorinated biphenyls at the highest quartile. Also for the combined serum POP induced agonistic AR transactivity significant association to BC risk was found, and cases elicited a higher frequency of samples with significant POP related hormone-like agonistic ER transactivity. The AhR toxic equivalent was lowest in cases. CONCLUSIONS: The level of serum POPs, particularly PFCs, might be risk factors in the development of BC in Inuit. Hormone disruption by the combined serum POP related xenoestrogenic and xenoandrogenic activities may contribute to the risk of developing breast cancer in Inuit. Further investigations are needed to document these study conclusions. PMID- 21978368 TI - Immune interference in Mycobacterium tuberculosis intracellular iron acquisition through siderocalin recognition of carboxymycobactins. AB - The innate immune system antibacterial protein Siderocalin (Scn) binds ferric carboxymycobactin (CMB) and also several catecholate siderophores. Although the recognition of catecholates by Scn has been thoroughly investigated, the binding interactions of Scn with the full spectrum of CMB isoforms have not been studied. Here we show that Scn uses different binding modes for the limited subset of bound CMB isoforms, resulting in a range of binding affinities that are much weaker than other siderophore targets of Scn. Understanding the binding interaction between Scn and CMBs provides clues for the influence of Scn on mycobacterial iron acquisition. PMID- 21978371 TI - Supporting hospice volunteers and caregivers through community-based participatory research. AB - Drawing on the results of community-based research with a local hospice organisation, this article addresses the need to enhance social support for caregivers of people with life-threatening illnesses. The goal of the research was to involve palliative care stakeholders in the identification, prioritisation and implementation of social support interventions for caregivers who provide palliative care support as hospice volunteers and as family members of those at end-of-life. Guided by a community-based participatory research approach, primary data were collected from 39 volunteer and family member caregivers through four focus groups and nine personal diaries in July 2008. Content analysis and modified constant comparison techniques resulted in emergent themes and priorities relating to challenges, existing coping strategies and resources, and potential support interventions. The findings revealed communication, emotional support, education, advocacy and personal fatigue as the most important challenges to be addressed through support interventions at the organisational (professional support, volunteer mentoring and continuing education) and household levels (caregiver assessments, telephone support and follow-up). There was convergence in how caregivers perceived and access existing social supports, yet a crucial divergence in the availability of resources among volunteers and family members. The findings are discussed in the light of the capacity for hospices to implement social supports and the potential efficacy of the community based participatory research approach for enhancing social support for caregivers in other parts of health-care and social care. PMID- 21978372 TI - Spectroscopic study of the CP43' complex and the PSI-CP43' supercomplex of the cyanobacterium Synechocystis PCC 6803. AB - The PSI-CP43' supercomplex of the cyanobacterium Synechocystis PCC 6803, grown under iron-starvation conditions, consists of a trimeric core Photosystem I (PSI) complex and an outer ring of 18 CP43' light-harvesting complexes. We have investigated the electronic structure and excitation energy transfer (EET) pathways within the CP43' (also known as the isiA gene product) ring using low temperature absorption, fluorescence, fluorescence excitation, and hole-burning (HB) spectroscopies. Analysis of the absorption spectra of PSI, CP43', and PSI CP43' complexes suggests that there are 13 chlorophylls (Chls) per CP43' monomer, i.e., a number that was observed in the CP43 complex of Photosystem II (PSII) (Umena, Y. et al. Nature 2011, 473, 55-60). This is in contrast with the recent modeling studies of Zhang et al. (Biochim. Biophys. Acta 2010, 1797, 457-465), which suggested that IsiA likely contains 15 Chls. Modeling studies of various optical spectra of the CP43' ring using the uncorrelated EET model (Zazubovich, V.; Jankowiak, R. J. Lumin. 2007, 127, 245-250) suggest that CP43' monomers (in analogy to the CP43 complexes of the PSII core) also possess two quasi-degenerate low-energy states, A' and B'. The site distribution functions of states A' and B' maxima/full width at half-maximum (fwhm) are at 684 nm/180 cm(-1) and 683 nm/80 cm(-1), respectively. Our analysis shows that pigments mostly contributing to the lowest-energy A' and B' states must be located on the side of the CP43' complex facing the PSI core, a finding that contradicts the model of Zhang et al. but is in agreement with the model suggested by Nield et al. (Biochemistry2003, 42, 3180 3188). We demonstrate that the A'-A' and B'-B' EET between different monomers is possible, though with a slower rate than intramonomer A'-B' and/or B'-A' energy transfer. PMID- 21978373 TI - Nano-structure fabrication of GaAs using AFM tip-induced local oxidation method: different doping types and plane orientations. AB - In this study, we have fabricated nano-scaled oxide structures on GaAs substrates that are doped in different conductivity types of p- and n-types and plane orientations of GaAs(100) and GaAs(711), respectively, using an atomic force microscopy (AFM) tip-induced local oxidation method. The AFM-induced GaAs oxide patterns were obtained by varying applied bias from approximately 5 V to approximately 15 V and the tip loading forces from 60 to 180 nN. During the local oxidation, the humidity and the tip scan speed are fixed to approximately 45% and approximately 6.3 MUm/s, respectively. The local oxidation rate is further improved in p-type GaAs compared to n-type GaAs substrates whereas the rate is enhanced in GaAs(100) compared to and GaAs(711), respectively, under the identical conditions. In addition, the oxide formation mechanisms in different doping types and plane orientations were investigated and compared with two dimensional simulation results. PMID- 21978374 TI - Down-regulation of estrogen receptor-alpha and rearranged during transfection tyrosine kinase is associated with withaferin a-induced apoptosis in MCF-7 breast cancer cells. AB - BACKGROUND: Withaferin A (WA), a naturally occurring withanolide, induces apoptosis in both estrogen-responsive MCF-7 and estrogen-independent MDA-MB-231 breast cancer cell lines with higher sensitivity in MCF-7 cells, but the underlying mechanisms are not well defined. The purpose of this study was to determine the anti-cancer effects of WA in MCF-7 breast cancer cells and explore alterations in estrogen receptor alpha (ERalpha) and its associated molecules in vitro as novel mechanisms of WA action. METHODS: The effects of WA on MCF-7 viability and proliferation were evaluated by 3-(4, 5-dimethylthiazol-2-yl)-5-(3 carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and trypan blue exclusion assays. Apoptosis was evaluated by Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) flow cytometry and Western blot analysis of poly (ADP-ribose) polymerase (PARP) cleavage. Cell cycle effects were analyzed by PI flow cytometry. Western blotting was also conducted to examine alterations in the expression of ERalpha and pathways that are associated with ERalpha function. RESULTS: WA resulted in growth inhibition and decreased viability in MCF-7 cells with an IC50 of 576 nM for 72 h. It also caused a dose- and time-dependent apoptosis and G2/M cell cycle arrest. WA-induced apoptosis was associated with down-regulation of ERalpha, REarranged during Transfection (RET) tyrosine kinase, and heat shock factor-1 (HSF1), as well as up-regulation of phosphorylated p38 mitogen-activated protein kinase (phospho-p38 MAPK), p53 and p21 protein expression. Co-treatment with protein synthesis inhibitor cycloheximide or proteasome inhibitor MG132 revealed that depletion of ERalpha by WA is post-translational, due to proteasome-dependent ERalpha degradation. CONCLUSIONS: Taken together, down-regulation of ERalpha, RET, HSF1 and up regulation of phospho-p38 MAPK, p53, p21 are involved in the pro-apoptotic and growth-inhibitory effects of WA in MCF-7 breast cancer cells in vitro. Down regulation of ERalpha protein levels by WA is caused by proteasome-dependent ERalpha degradation. PMID- 21978375 TI - Compounds in different aphasia categories: a study on picture naming. AB - This study investigated the production of compounds in Italian-speaking patients affected by different aphasia categories (i.e., Broca's, Wernicke's, and anomic aphasia) in a confrontation naming task. Questions of theoretical interest concerning the processing of compounds within the framework of the "lemma theory" as well as the role of morphological productivity in compound processing are addressed. Results indicate that all persons with aphasia retain knowledge of the morphological status of words, even when they fail to retrieve the corresponding phonological form (the "compound effect"). A difference was found among aphasia categories in the type of errors produced (omission vs. substitution) and in the position (first or second) of these errors within the compound words. In Broca's aphasia, the first component is omitted more frequently than the second one, but only in verb-noun compounds. Anomic and Wernicke's aphasia, unlike in Broca's aphasia, seem to retain sensitivity to morphological productivity. PMID- 21978376 TI - Electronic properties of hydrogen-bonded complexes of benzene(HCN)(1-4): comparison with benzene(H2O)(1-4). AB - The electronic properties, specifically, the dipole and quadrupole moments and the ionization energies of benzene (Bz) and hydrogen cyanide (HCN), and the respective binding energies, of complexes of Bz(HCN)(1-4), have been studied through MP2 and OVGF calculations. The results are compared with the properties of benzene-water complexes, Bz(H(2)O)(1-4), with the purpose of analyzing the electronic properties of microsolvated benzene, with respect to the strength of the CH/pi and OH/pi hydrogen-bond (H-bond) interactions. The linear HCN chains have the singular ability to interact with the aromatic ring, preserving the symmetry of the latter. A blue shift of the first vertical ionization energies (IEs) of benzene is observed for the linear Bz(HCN)(1-4) clusters, which increases with the length of the chain. NBO analysis indicates that the increase of the IE with the number of HCN molecules is related to a strengthening of the CH/pi H-bond, driven by cooperative effects, increasing the acidity of the hydrogen cyanide H atom involved in the pi H-bond. The longer HCN chains (n >= 3), however, can bend to form CH/N H-bonds with the Bz H atoms. These cyclic structures are found to be slightly more stable than their linear counterparts. For the nonlinear Bz(HCN)(3-4) and Bz(H(2)O)(2-4) complexes, an increase of the binding energy with the number of solvent molecules and a decrease of the IE of benzene, relative to the values for the Bz(HCN) and Bz(H(2)O) complexes, respectively, are observed. Although a strengthening of the CH/pi and OH/pi H bonds, with increasing n, also takes place for the Bz(H(2)O)(2-4) and Bz(HCN)(3 4) nonlinear complexes, Bz proton donor, CH/O, and CH/N interactions are at the origin of this decrease. Thus CH/pi and OH/pi H-bonds lead to higher IEs of Bz, whereas the weaker CH/N and CH/O H-bond interactions have the opposite effect. The present results emphasize the importance of both aromatic XH/pi (X = C, O) and CH/X (X = N, O) interactions for understanding the structure and electronic properties of Bz(HCN)(n) and Bz(H(2)O)(n) complexes. PMID- 21978377 TI - Molecular basis of beta-thalassemia in Karnataka, India. AB - In beta-thalassemia, point mutations in the beta-globin gene are largely responsible for either decreased or no beta-globin synthesis. The beta-globin gene has three exons and two introns. The molecular characterization of beta thalassemia is absolutely necessary for carrier screening, for genetic counseling, and to offer prenatal diagnosis. The objective of the present study was to identify the rare mutations in beta-globin gene of beta-thalassemia patients. We have sequenced the entire beta-globin gene in 36 clinically identified thalassemia patients from the Karnataka region using polymerase chain reaction and sequencing. Our analysis revealed 11 beta-thalassemia variants. The most common being IVSII-16 G>C, IVSI-5G>C, IVSII-74 T>G, codon 3 (T>C), and Poly A site (T>C). In addition, we have also documented a novel deletion at codon 6 ( CT) (HBB:c.16delCT). These data are useful in future molecular screening of the population for implementing a thalassemia prevention and control program. Further it is found that family studies and comprehensive hematological analyses would provide useful insights for accurate molecular diagnosis of thalassemia phenotype and offers an interesting subject for further investigations in the Indian populations. PMID- 21978378 TI - Facile general route toward tunable Magneli nanostructures and their use as thermoelectric metal oxide/carbon nanocomposites. AB - Engineering nanoscale interfaces is a requisite for harnessing electrical and thermal transports within nanostructured materials, especially those destined for thermoelectric applications requiring an unusual combination of low thermal conductivity and electrical resistivity. Nanocomposites open up possibilities in this area, but are still bound to a very narrow range of materials. Here, we report a new approach combining the sol-gel process toward hybrid materials with spark plasma sintering (SPS) to yield functional nanocomposites based on substoichiometric titanium oxides Ti(n)O(2n-1), so-called Magneli phases. The potential of this new approach is demonstrated by three results. First, multiple Ti(n)O(2n-1) compounds (n = 3, 4, 5, 6, 8) are obtained for the first time as sole nano-Magneli crystalline phases with controlled specific surface areas from 55 to 300 m(2).g(-1), classified as potential thermoelectric n-type metal oxides and paving the way toward advanced systems for energy-harvesting devices and optoelectronics. Second, this work combines the use of sol-gel and SPS processes to yield percolated nanocomposites based on metal oxide nanoparticles embedded in a carbon matrix with low electrical resistivity (2 * 10(-4) Omega.m for a Ti(4)O(7) compound) and reduced thermal conductivity (1 W.m(-1).K(-1)) with respect to bulk phases. Finally, the discovered materials are reliable with thermoelectric figures of merit (ZT = 0.08) relatively high for n-type Ti-O-based systems and metal oxides. Thereby this study represents a proof of concept for the development of promising, cheaper, and more efficient thermoelectric conversion devices. PMID- 21978379 TI - One-pot syntheses of pseudopteroxazoles from pseudopterosins: a rapid route to non-natural congeners with improved antimicrobial activity. AB - Rapid one-pot methodologies to prepare pseudopteroxazole (1) and novel congeners from abundant natural pseudopterosins have been devised. This is highlighted here with the first synthesis of the marine natural product homopseudopteroxazole (2) utilizing a novel, silver(I)-mediated catechol to benzoxazole transformation. Pseudopteroxazoles and isopseudopteroxazoles exhibit potent activity against a range of important Gram-positive pathogens including Mycobacterium spp. and vancomycin-resistant Enterococcus faecium. Several non-natural pseudopteroxazoles exhibited strong activity against methicillin-resistant Staphylococcus aureus, thereby displaying a broader spectrum of antibiotic activity compared to pseudopteroxazole. PMID- 21978380 TI - Risks for HIV infection among gay, bisexual, and other men who have sex with men in Moscow and St. Petersburg, Russia. AB - The majority of early cases of HIV in Russia were among men who have sex with men (MSM). Despite this and the current resurgence of HIV among MSM globally, little systematic work has been done to assess current HIV risks. We conducted a rapid assessment of HIV and associated risk behaviors among MSM in Russia. An anonymous, cross-sectional study was performed among MSM in Moscow and St. Petersburg (January 2008). Participants were enrolled by local NGO partners via peer-recruitment, underwent a brief behavioral survey, and were offered rapid, oral HIV screening. Factors associated with HIV infection were assessed using logistic regression. A total of 401 participants were enrolled. HIV prevalence was comparable in the two cities (6.0% in Moscow, 5.5% in St. Petersburg). Approximately half (49.3%) were under age 25, 75.1% of all men reported unprotected anal intercourse (UAI), and 21.5% reported engaging in unprotected exchange sex in the prior 12 months. HIV infection was the highest (7.7%) among the youngest MSM, those aged 18-22 years. Never having tested for HIV (AOR=6.2; 95% CI: 1.8, 21.9) and ever injecting drugs (AOR=11.3; 95% CI: 2.6, 50.4) were independently associated with HIV infection. We found significant overall HIV prevalence among MSM in Moscow and St. Petersburg, particularly among the youngest men. The majority of men reported ongoing high-risk behaviors, indicating the potential for further spread. HIV prevention efforts need to specifically focus on urban MSM in Russia, encourage testing, and target injection risks to address this epidemic. PMID- 21978381 TI - Structural changes in apolipoproteins bound to nanoparticles. AB - Nanoparticles are widely used in the pharmaceutical and food industries, but the consequences of exposure to the human body have not been thoroughly investigated. Apolipoprotein A-I (apoAI), the major protein in high-density lipoprotein (HDL), and other lipoproteins are found in the corona around many nanoparticles, but data on protein structural and functional effects are lacking. Here we investigate the structural consequences of the adsorption of apoAI, apolipoprotein B100 (apoB100), and HDL on polystyrene nanoparticles with different surface charges. The results of circular dichroism, fluorescence spectroscopy, and limited proteolysis experiments indicate effects on both secondary and tertiary structures. Plain and negatively charged nanoparticles induce helical structure in apoAI (negative net charge) whereas positively charged nanoparticles reduce the amount of helical structure. Plain and negatively charged particles induce a small blue shift in the tryptophan fluorescence spectrum, which is not noticed with the positively charged particles. Similar results are observed with reconstituted HDL. In apoB100, both secondary and tertiary structures are perturbed by all particles. To investigate the generality of the role of surface charge, parallel experiments were performed using human serum albumin (HSA, negative net charge) and lysozyme (positive net charge). Again, the secondary structure is most affected by nanoparticles carrying an opposite surface charge relative to the protein. Nanoparticles carrying the same net charge as the protein induce only minor structural changes in lysozyme whereas a moderate change is observed for HSA. Thus, surface charge is a critical parameter for predicting structural changes in adsorbed proteins, yet the effect is specific for each protein. PMID- 21978382 TI - Effect of herbal extract granules combined with probiotic mixture on irritable bowel syndrome with diarrhea: study protocol for a randomized controlled trial. AB - BACKGROUND: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and change of bowel habits without organic disease. Many patients seek alternative IBS treatments because of the limitations of conventional treatments. Gwakhyangjeonggisan (GJS), a herbal formula, has long been used for alleviating diarrhea-predominant IBS (D-IBS) in traditional medicine. Duolac7S, which comprises 7 bacterial species as probiotics, has been frequently used for D-IBS. Although GJS and Duolac7S have been administered simultaneously in many D-IBS patients, no study has investigated the effects of GJS and Duolac7S combination therapy on D-IBS. METHODS/DESIGN: The current trial is a randomized, double-blinded, placebo-controlled, 4-arm study. After a 2-week run-in period, 60 patients with D-IBS will be randomly assigned to one of the 4 combination groups consisting of GJS (water extract granules, 3 g/pack, 3 times a day) with Duolac7S (powder form, 1 capsule, 2 times a day) or their placebos and followed up for 2 weeks. The assigned treatments will last for 8 weeks. The primary outcomes are adequate relief of IBS pain and discomfort and the proportion of responders (on a weekly basis). The secondary outcomes are visual analog scale for IBS symptoms (on a daily basis), quality of life (at 0, 8, and 10 weeks), intestinal permeability, and composition of intestinal microbiota (at 0 and 8 weeks). DISCUSSION: The present study is designed to examine the safety and efficacy of GJS and Duolac7S combination therapy on D-IBS. Our study provides the clinical evidence of a new therapeutic strategy for D-IBS. PMID- 21978384 TI - Synthesis of PbSeTe single ternary alloy and core/shell heterostructured nanocubes. AB - We report a robust method for synthesis of monodisperse PbSeTe single ternary alloy and core/shell heterostructured nanocubes, respectively. The key synthetic strategy to produce such different classes of nanocubes is to precisely control the time of reaction and successive growth. The crystallinity, shape/size distributions, structural characteristics, and compositions of as-prepared nanocubes, both ternary alloy and core/shell, were carefully studied. A plausible growth mechanism for developing each type of lead chalcogenide nanocubes is proposed. These delicately designed PbSeTe nanoscale architectures offer tunable compositions in PbSeTe ternary alloy and nano-interfaces in core/shell nanocubes, which are the critical factors in controlling thermal conductivity for applications in thermoelectrics. PMID- 21978383 TI - Minimally invasive intra-arterial regional therapy for metastatic melanoma: isolated limb infusion and percutaneous hepatic perfusion. AB - INTRODUCTION: In-transit melanoma or melanoma presenting as unresectable liver metastases are clinical situations with limited therapeutic options. Regional intra-arterial therapies provide efficacious treatment alternatives for these patients. Through surgical techniques of vascular isolation, regional therapies deliver high-dose chemotherapy to tumor cells while minimizing systemic exposure. However, percutaneous techniques such as isolated limb infusion (ILI) and percutaneous hepatic perfusion (PHP) have been developed, which provide a minimally invasive means of obtaining vascular isolation of target organs. AREAS COVERED: Areas covered in this review include the techniques of ILI and PHP, the chemotherapeutic agents utilized during these regional therapies and the clinical responses seen after ILI and PHP. The pharmacokinetics of regional chemotherapy utilized during ILI and PHP is also reviewed with an additional focus on novel ways to optimize drug delivery to improve response rates and attempts to define the potential systemic manifestations of regional therapeutics. EXPERT OPINION: Unresectable hepatic and limb in-transit metastases from melanoma are very difficult to treat. Systemic chemotherapy has largely been ineffective. Both the minimally invasive, percutaneous techniques of ILI and PHP are excellent methods used to deliver extremely high-dose chemotherapy regionally to patients harboring metastatic melanoma confined to an extremity or liver, respectively. Studies, from prospectively maintained databases as well as Phase II and III trials, have shown the great efficacy of these techniques. PMID- 21978386 TI - Spectrofluorimetric determination of sertraline in dosage forms and human plasma through derivatization with 9-fluorenylmethyl chloroformate. AB - BACKGROUND: Sertraline is primarily used to treat major depression in adult outpatients as well as obsessive-compulsive, panic and social anxiety disorders in both adults and children. A survey of the literature reveals that most of the reported methods are either insufficiently sensitive or tedious and require highly sophisticated and dedicated instrumentation. The proposed method is considered to be specific for determination of SER in presence of its metabolite (deaminated form). RESULTS: A sensitive, simple and specific spectrofluorimetric method was developed for the determination of sertraline (SER) in pharmaceutical formulations and biological fluids. The method is based on its reaction with 9 fluorenylmethyl chloroformate (FMOC-Cl) in borate buffer of pH 8.0 to yield a highly fluorescent derivative peaking at 315 nm after excitation at 265 nm. The different experimental parameters affecting the development and stability of the reaction product were carefully studied and optimized. The fluorescence concentration plot was rectilinear over the range of 0.05-1.0 MUg mL-1 with a lower detection limit of 5.34 * 10-3 MUg mL-1 and limit of quantitation of 0.016 MUg mL-1. CONCLUSIONS: The proposed method was successfully applied to the analysis of commercial tablets and the results obtained were in good agreement with those obtained using the reference method. Furthermore, the method was applied for the determination of SER in spiked and real human plasma. The mean % recovery (n = 3) was 94.33 +/- 1.53 and 92.00 +/- 2.65, respectively. A proposal of the reaction pathway was postulated. PMID- 21978385 TI - The ICF as a common language for rehabilitation goal-setting: comparing client and professional priorities. AB - BACKGROUND: Joint rehabilitation goals are an important component for effective teamwork in the rehabilitation field. The activities and participation domain of the ICF provides a common language for professionals when setting these goals. Involving clients in the formulation of rehabilitation goals is gaining momentum as part of a person-centred approach to rehabilitation. However, this is particularly difficult when clients have an acquired communication disability. The expressive communication difficulties negatively affect the consensus building process. As a result, obtaining information regarding rehabilitation goals from professionals and their clients warrants further investigation for this particular population. METHODS: This comparative study investigated clients and their assigned rehabilitation professionals' perception of the importance of ICF activities and participation domains for inclusion in their rehabilitation program. Twelve clients in an acute rehabilitation centre and twenty of their corresponding rehabilitation professionals participated in an activity using the Talking MatsTM visual framework for goal setting. Each participant rated the importance of the nine activities and participation domains of the ICF for inclusion in their current rehabilitation program. RESULTS: The ICF domains which consistently appear as very important across these groups are mobility, self-care and communication. Domains which consistently appear in the lower third of the rankings include spare time, learning and thinking and domestic life. Results indicate however that no statistical significant differences exist in terms of the individual domains across each of the participant groups. Within group differences however indicated that amongst the speech-language therapists and physiotherapists there was a statistical significant difference between spare time activities and communication and mobility. CONCLUSIONS: Findings indicate that consensus is possible amongst professionals and clients even within an acute rehabilitation setting. In addition, the Talking MatsTM visual framework appears to be a valid protocol for including clients with acquired communication disabilities in the process of obtaining consensus during goal-setting. PMID- 21978387 TI - Seasonal variations of urinary albumin creatinine ratio in Japanese subjects with Type 2 diabetes and early nephropathy. AB - AIMS: It has been recognized that blood pressure shows a seasonal variation, but it remains unknown whether diabetic nephropathy shows a seasonal variation. In the present study, we investigated the change in urinary albumin/creatinine ratio in relation to the season in Japanese patients with Type 2 diabetes. METHODS: A total of 430 subjects (275 male, 155 female) with Type 2 diabetes and early nephropathy (defined by UACR 30-300 mg/g creatinine) were included. One year was divided into four seasons and each season was defined as winter (December February), spring (March-May), summer (June-August), and fall (September November), and systolic and diastolic blood pressure, serum creatinine levels, and the urinary albumin/creatinine ratio were examined. The estimated glomerular filtration rate was also calculated and evaluated. RESULTS: The mean age (+/- SE) was 64.8 +/- 0.8 years. The mean systolic blood pressure was significantly higher in winter than in summer (136 +/- 0.68 vs. 133 +/- 0.68 mmHg, P < 0.001). The urinary albumin/creatinine ratio showed a significantly higher value in winter than in summer (72.8 +/- 4.4 vs. 54.6 +/- 3.4 mg/g creatinine, P < 0.001). The curve of seasonal variation of this ratio showed a similar change to that of systolic blood pressure. No significant seasonal variation was observed in estimated glomerular filtration rate and diastolic blood pressure. CONCLUSIONS: Our results suggest that there is a hitherto unknown seasonal variation in the urinary albumin/creatinine ratio, and that it may be necessary to consider this seasonal change, especially when performing an intervention study of nephropathy. PMID- 21978388 TI - Properties of the monomeric form of human 14-3-3zeta protein and its interaction with tau and HspB6. AB - Dimers formed by seven isoforms of the human 14-3-3 protein participate in multiple cellular processes. The dimeric form has been extensively characterized; however, little is known about the structure and properties of the monomeric form of 14-3-3. The monomeric form is involved in the assembly of homo- and heterodimers, which could partially dissociate back into monomers in response to phosphorylation at Ser58. To obtain monomeric forms of human 14-3-3zeta, we produced four protein constructs with different combinations of mutated (M) or wild-type (W) segments E(5), (12)LAE(14), and (82)YREKIE(87). Under a wide range of expression conditions in Escherichia coli, the MMM and WMM mutants were insoluble, whereas WMW and MMW mutants were soluble, highly expressed, and purified to homogeneity. WMW and MMW mutants remained monomeric over a wide range of concentrations while retaining the alpha-helical structure characteristic of wild-type 14-3-3. However, WMW and MMW mutants were highly susceptible to proteolysis and had much lower thermal stabilities than the wild-type protein. Using WMW and MMW mutants, we show that the monomeric form interacts with the tau protein and with the HspB6 protein, in both cases forming complexes with a 1:1 stoichiometry, in contrast to the 2:1 and/or 2:2 complexes formed by wild-type 14 3-3. Significantly, this interaction requires phosphorylation of tau protein and HspB6. Because of minimal changes in structure, MMW and especially WMW mutant proteins are promising candidates for analyzing the effect of monomerization on the physiologically important properties of 14-3-3zeta. PMID- 21978389 TI - Development of gastro intestinal sustained release tablet formulation containing acryl-EZE and pH-dependent swelling HPMC K 15 M. AB - BACKGROUND: The aim of this study was to evaluate physical properties and release from matrix tablets containing different ratios of HPMC 15 M and Acryl-EZE. A further aim is to assess their suitability for pH dependent controlled release. METHODS: Matrix tablets containing HPMC 15 M and Acryl-EZE were manufactured using a fluidized bed. The release from this matrix using Sodium Diclofenac (SD) as model drug is studied in two dissolution media (0.1 N HCl or pH = 6.8 phosphate buffer solution); the release rate, mechanism, and pH dependence were characterized by fitting four kinetic models and by using a similarity factor analysis. RESULTS: The obtained results revealed that the presence of Acryl-EZE in the matrix tablets is effective in protecting the dosage forms from release in acid environments such as gastric fluid. In pH = 6.8 phosphate buffer, the drug release rate and mechanism of release from all matrices is mainly controlled by HPMC 15 M. The model of Korsmeyer-Peppas was found to fit experimental dissolution results. PMID- 21978390 TI - The transhepatic endotoxin gradient is present despite liver cirrhosis and is attenuated after transjugular portosystemic shunt (TIPS). AB - BACKGROUND: Translocation of gut-derived bacterial products such as endotoxin is a major problem in liver cirrhosis. METHODS: To assess the hepatic clearance of bacterial products in individuals with cirrhosis, we tested concentrations of Gram-negative bacterial lipopolysaccharide (LPS), LPS-binding protein (LBP), and the precursor of nitric oxide (NO), L-arginine, in a cohort of 8 stable patients with liver cirrhosis before and after elective transjugular portosystemic shunt (TIPS) implantation, including central venous, hepatic venous, and portal venous measurements. RESULTS: Using an adapted LPS assay, we detected high portal venous LPS concentrations (mean 1743 +/- 819 pg/mL). High concentrations of LPS were detectable in the central venous blood (931 +/- 551 pg/mL), as expected in persons with cirrhosis. The transhepatic LPS gradient was found to be 438 +/- 287 pg/mL, and 25 +/- 12% of portal LPS was cleared by the cirrhotic liver. After TIPS, central venous LPS concentrations increased in the hepatic and central veins, indicating shunting of LPS with the portal blood through the stent. This paralleled a systemic increase of L-arginine, whereas the NO synthase inhibitor asymmetric dimethylarginine (ADMA) remained unchanged, suggesting that bacterial translocation may contribute to the pathogenesis of circulatory dysfunction post TIPS. CONCLUSIONS: This study provides quantitative estimates of the role of the liver in the pathophysiology of bacterial translocation. The data indicate that the cirrhotic liver retains the capacity for clearance of bacterial endotoxin from the portal venous blood and that TIPS implantation attenuates this clearance. Thus, increased endotoxin concentrations in the systemic circulation provide a possible link to the increased encephalopathy in TIPS patients. PMID- 21978391 TI - Development of a novel bioelectrochemical membrane reactor for wastewater treatment. AB - A novel bioelectrochemical membrane reactor (BEMR), which takes advantage of a membrane bioreactor (MBR) and microbial fuel cells (MFC), is developed for wastewater treatment and energy recovery. In this system, stainless steel mesh with biofilm formed on it serves as both the cathode and the filtration material. Oxygen reduction reactions are effectively catalyzed by the microorganisms attached on the mesh. The effluent turbidity from the BEMR system was low during most of the operation period, and the chemical oxygen demand and NH(4)(+)-N removal efficiencies averaged 92.4% and 95.6%, respectively. With an increase in hydraulic retention time and a decrease in loading rate, the system performance was enhanced. In this BEMR process, a maximum power density of 4.35 W/m(3) and a current density of 18.32 A/m(3) were obtained at a hydraulic retention time of 150 min and external resister of 100 Omega. The Coulombic efficiency was 8.2%. Though the power density and current density of the BEMR system were not very high, compared with other high-output MFC systems, electricity recovery could be further enhanced through optimizing the operation conditions and BEMR configurations. Results clearly indicate that this innovative system holds great promise for efficient treatment of wastewater and energy recovery. PMID- 21978392 TI - Inhibition of cyclo-oxygenase 2 reduces tumor metastasis and inflammatory signaling during blockade of vascular endothelial growth factor. AB - Vascular endothelial growth factor (VEGF) blockade is an effective therapy for human cancer, yet virtually all neoplasms resume primary tumor growth or metastasize during therapy. Mechanisms of progression have been proposed to include genes that control vascular remodeling and are elicited by hypoperfusion, such as the inducible enzyme cyclooxygenase-2 (COX-2). We have previously shown that COX-2 inhibition by the celecoxib analog SC236 attenuates perivascular stromal cell recruitment and tumor growth. We therefore examined the effect of combined SC236 and VEGF blockade, using the metastasizing orthotopic SKNEP1 model of pediatric cancer. Combined treatment perturbed tumor vessel remodeling and macrophage recruitment, but did not further limit primary tumor growth as compared to VEGF blockade alone. However, combining SC236 and VEGF inhibition significantly reduced the incidence of lung metastasis, suggesting a distinct effect on prometastatic mechanisms. We found that SC236 limited tumor cell viability and migration in vitro, with effects enhanced by hypoxia, but did not change tumor proliferation or matrix metalloproteinase expression in vivo. Gene set expression analysis (GSEA) indicated that the addition of SC236 to VEGF inhibition significantly reduced expression of gene sets linked to macrophage mobilization. Perivascular recruitment of macrophages induced by VEGF blockade was disrupted in tumors treated with combined VEGF- and COX-2-inhibition. Collectively, these findings suggest that during VEGF blockade COX-2 may restrict metastasis by limiting both prometastatic behaviors in individual tumor cells and mobilization of macrophages to the tumor vasculature. PMID- 21978393 TI - Metabolomic study of interactive effects of phenol, furfural, and acetic acid on Saccharomyces cerevisiae. AB - Metabolic profiling was carried out to investigate the interactive effects of three representative inhibitors (furfural, phenol, and acetic acid) in lignocellulosic hydrolysate on Saccharomyces cerevisiae during ethanol fermentation. Our results revealed that three inhibitors exhibited significantly synergistic effects on the growth, fermentation, and some metabolites of yeast. Acetic acid exerted the most severe effects on yeast in the combination of three inhibitors, enhancing amino acids metabolism and inhibiting central carbon metabolism. The effects on yeast cells by acetic acid were enhanced by the presence of phenol and furfural, which might be owing to the loss of membrane integrity and the inhibition on metabolism. Further investigation indicated that the combination of inhibitors also exhibited antagonistic effects mainly on threonine, cadaverine, inositol, and tryptophan, weakening or reversing the effects of individual inhibitor. It might be due to the more severe damage by the combined inhibitors, and different repairing mechanism of cells in the presence of individual and combined inhibitors. Better understanding of the synergistic and antagonistic effects of the inhibitors will be helpful for the improvement of tolerant strains and the optimization of lignocellulosic fermentation. PMID- 21978394 TI - Lipidomic analysis of apoptotic hela cells induced by Paclitaxel. AB - Apoptosis has been shown to be accompanied by changes in cellular phospholipids. In this study, lipidomic strategy was applied to investigate the early changes in Hela cell phospholipid metabolism in response to paclitaxel-induced apoptosis. A total of 240 phospholipid species were profiled and 202 of them were quantified using the NPLC-ESI/MS(n) procedure. Principal component analysis and partial least squares combined with variable influence on projection were applied to find the potential biomarkers for discrimination between the control and paclitaxel treated cells. Lysophosphatidylethanolamine and lysophosphatidylcholine species with strong decreasing trends after 6 h of treatment were identified as possible biomarkers for discrimination, which could be backed up by the decreased expression of cPLA(2). In addition, some of phosphatidylethanolamine, phosphatidylinositol, and phosphatidylcholine species with unsaturated fatty acid chains and phosphatidic acid species with saturated fatty acid chains were also indentified as potential biomarkers, and their changes might be closely related to the alteration of cell membrane fluidity happened in apoptotic process. These results showed clearly that phospholipids and related phospholipases played important roles in paclitaxel-induced apoptosis in Hela cells. Our study also demonstrates that lipidomics provide a powerful tool for better understanding anticancer mechanisms of chemotherapeutic agents and for biomarker screening. PMID- 21978395 TI - Grade-specific expression profiles of miRNAs/mRNAs and docking study in human grade I-III astrocytomas. AB - Although several miRNAs have been identified to be involved in glioblastoma tumorigenesis, little is known about the global expression profiles of miRNAs and their functional targets in astrocytomas at earlier stages of malignancy. In this study the global expression of miRNAs and mRNAs in normal brain tissue samples and grade I-III astrocytomas were analyzed parallelly using microarrays, and the grade-specific expression profiles of them were obtained by unsupervised hierarchical clustering. It was also confirmed that miR-107, miR-124, miR-138, and miR-149 were downregulated significantly in grade I-IV astrocytomas, and overexpression of miR-124 and miR-149 inhibited glioblastoma cell proliferation and migration. Furthermore, grade-specific changes were discovered in the central biological processes, regulatory networks, and signaling pathways associated with dysregulated genes, and a regulatory network of putative functional miRNA-mRNA pairs was defined. In conclusion, our results may contribute to a better understanding of the molecular mechanisms involved in astrocytoma tumorigenesis and malignant progression. PMID- 21978396 TI - Proteomic analysis of membrane proteins from Streptococcus pneumoniae with multiple separation methods plus high accuracy mass spectrometry. AB - Abstract Streptococcus pneumoniae is a Gram-positive human pathogen that causes a variety of serious mucosal and invasive diseases in human. Bacterial membrane proteins play crucial roles in host-pathogen interactions and bacterial pathogenesis, and thus are potential drug targets or vaccine candidates. In this study, membranes from Streptococcus pneumoniae D39 were enriched by mechanical grinding and ultracentrifugation, and then the membrane proteins were extracted with trifluroethanol and chloroform. Around 60% of the extracted proteins were identified to be membrane proteins with 2-DE coupled with MALDI-MS/MS and 2D-LC ESI-MS/MS. These identified membrane proteins can be functionally categorized into various groups involved in nutriment transport, signal transduction, protein folding or secretion, oxidation, carbohydrate metabolism, and other physiological processes. A protein interaction network was constructed for understanding the regulation relationship of the membrane proteins. This study represents the first global characterization of membrane proteome from Gram-positive streptococcus species of bacteria, providing valuable clues for further investigation aiming at identifying drug/vaccine targets for the bacterial infection. PMID- 21978397 TI - Metabolic changes during a field experiment in a world-class windsurfing athlete: a trial with multivariate analyses. AB - Physical exercise affects hematological equilibrium and metabolism. This study evaluated the biochemical and hematological responses of a male world-class athlete in sailing who is ranked among the top athletes on the official ISAF ranking list of windsurfing, class RS:X. The results describe the metabolic adaptations of this athlete in response to exercise in two training situations: the first when the athlete was using the usual training and dietary protocol, and the second following training and nutritional interventions based on a careful analysis of his diet and metabolic changes measured in a simulated competition. The intervention protocol for this study consisted of a 3-month facility-based program using neuromuscular training (NT), aerobic training (AT), and nutritional changes to promote anabolism and correct micronutrient malnutrition. Nutritional and training intervention produced an increase in the plasma availability of branched-chain amino acids (BCAAs), aromatic amino acids (AAAs), alanine, glutamate, and glutamine during exercise. Both training and nutritional interventions reduced ammonemia, uricemia, and uremia. In addition, we are able to correct a significant drop in potassium levels during races by correct supplementation. Due to the uniqueness of this experiment, these results may not apply to other windsurfers, but we nonetheless had the opportunity to characterize the metabolic adaptations of this athlete. We also proposed the importance of in-field metabolic analyses to the understanding, support, and training of world-class elite athletes. PMID- 21978399 TI - A systems biology approach to model neural stem cell regulation by notch, shh, wnt, and EGF signaling pathways. AB - The Notch, Sonic Hedgehog (Shh), Wnt, and EGF pathways have long been known to influence cell fate specification in the developing nervous system. Here we attempted to evaluate the contemporary knowledge about neural stem cell differentiation promoted by various drug-based regulations through a systems biology approach. Our model showed the phenomenon of DAPT-mediated antagonism of Enhancer of split [E(spl)] genes and enhancement of Shh target genes by a SAG agonist that were effectively demonstrated computationally and were consistent with experimental studies. However, in the case of model simulation of Wnt and EGF pathways, the model network did not supply any concurrent results with experimental data despite the fact that drugs were added at the appropriate positions. This paves insight into the potential of crosstalks between pathways considered in our study. Therefore, we manually developed a map of signaling crosstalk, which included the species connected by representatives from Notch, Shh, Wnt, and EGF pathways and highlighted the regulation of a single target gene, Hes-1, based on drug-induced simulations. These simulations provided results that matched with experimental studies. Therefore, these signaling crosstalk models complement as a tool toward the discovery of novel regulatory processes involved in neural stem cell maintenance, proliferation, and differentiation during mammalian central nervous system development. To our knowledge, this is the first report of a simple crosstalk map that highlights the differential regulation of neural stem cell differentiation and underscores the flow of positive and negative regulatory signals modulated by drugs. PMID- 21978398 TI - Investigation of plasma biomarkers in HIV-1/HCV mono- and coinfected individuals by multiplex iTRAQ quantitative proteomics. AB - The analysis of plasma samples from HIV-1/HCV mono- and coinfected individuals by quantitative proteomics is an efficient strategy to investigate changes in protein abundances and to characterize the proteins that are the effectors of cellular functions involved in viral pathogenesis. In this study, the infected and healthy plasma samples (in triplicate) were treated with ProteoMiner beads to equalize protein concentrations and subjected to 4-plex iTRAQ labeling and liquid chromatography/mass spectrometry (LC-MS/MS) analysis. A total of 70 proteins were identified with high confidence in the triplicate analysis of plasma proteins and 65% of the proteins were found to be common among the three replicates. Apolipoproteins and complement proteins are the two major classes of proteins that exhibited differential regulation. The results of quantitative analysis revealed that APOA2, APOC2, APOE, C3, HRG proteins were upregulated in the plasma of all the three HIV-1 mono-, HCV mono-, and coinfected patient samples compared to healthy control samples. Ingenuity pathway analysis (IPA) of the upregulated proteins revealed that they are implicated in the hepatic lipid metabolism, inflammation, and acute-phase response signaling pathways. Thus, we identified several differentially regulated proteins in HIV-1/HCV mono and coinfected plasma samples that may be potential biomarkers for liver disease. PMID- 21978400 TI - Hemiarthroplasty and total hip arthroplasty for treating primary intracapsular fracture of the hip: a systematic review and cost-effectiveness analysis. AB - BACKGROUND: Hip fracture is a common problem in people aged > 60 years. The treatment options for individuals with high pre-fracture mobility, function and independence are hemiarthroplasty (HA) and total hip arthroplasty (THA). OBJECTIVE: The aim of this report is to assess the clinical effectiveness and cost-effectiveness evidence of THA compared with HA in patients with displaced intracapsular fracture who are cognitively intact with high pre-fracture mobility or function. DATA SOURCES: A systematic search was made of 11 databases of published and unpublished literature from their inception to december 2010: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library, Biological Science Citation Index, Social Science Citation Index, Conference Proceedings Citation Index - Science, UK Clinical Trials Research Network and the National Research Register archive, Current Controlled Trials and ClinicalTrials.gov. REVIEW METHODS: A systematic review of randomised controlled trials (RCTs) to assess the effectiveness of THA compared with HA in terms of dislocations, revisions, pain and function, and quality of life. Meta analysis, independent subgroup analyses and exploratory cost-effectiveness modelling were performed. RESULTS: The literature search identified 532 unique citations, of which eight RCTs with almost 1000 participants satisfied the criteria for the effectiveness review. Meta-analysis found a statistically significant increased risk of dislocation for patients treated with THA compared with HA (p = 0.01), but a reduced risk of revision (p = 0.0003). There were no differences in terms of mortality. In all trials, individuals treated with THA reported better function and mobility and less pain than those treated with HA. Four trials reporting utility data found similar trends. Sensitivity analyses indicated that there were no statistically significant differences in outcomes based on follow-up, study quality, surgical approach taken, type of head or the use of cement. Four papers reported a cost-utility analysis or the cost effectiveness of THA compared with HA. Exploratory modelling was undertaken that showed that THA is likely to be cost-effective compared with HA even when the limitations of the data and methodology are considered. LIMITATIONS: The costs and disutilities associated with revisions and dislocations were not included in the economic evaluation. CONCLUSIONS: THA appears to be more cost-effective than HA. It is likely that THA will be associated with increased costs in the initial 2-year period, but lower longer-term costs, owing to potentially lower revision rates. However, these longer-term costs have not been modelled. The capacity and experience of surgeons to perform THA have not been explored and these would need to be addressed at local level were THA to become recommended for active, elderly patients in whom THA is not contraindicated. Further studies examining the impact of surgeon experience on performing the two procedures may offer more robust evidence on outcomes. FUNDING: The National Institute for Health Research Health Technology Assessment programme. PMID- 21978401 TI - Microfluidic circuit analysis I: ion current relationships for thin slits and pipes. AB - Existing microfluidic circuit theories consider conservation of volume and conservation of total charge at each channel intersection (node) that exists within a circuit. However, in a strict sense conservation of number (or charge) for each ion species that is present should also be applied. To be able to perform such a conservation the currents due to the movement of each ion species (electrokinetic ion currents) that occur within each channel need to be known. Hence, we here present analytical and numerical methods for calculating these ion currents (and fluid flowrates) in Newtonian binary electrolyte solutions flowing within two-dimensional thin slits and pipes. Analytical results are derived in the limits of low potential, high potential, and thin double layers. We show that irrespective of double layer overlap, the Boltzmann distribution is valid provided that a local geometric mean is used for the reference ion concentration. While the real significance of the work lies in its application to multi-channel microfluidic circuit theory (see the accompanying paper of Biscombe et al. [1]), the present results show that even in single channels, ion current behaviour can be surprisingly complex. PMID- 21978402 TI - Ultrathin and nanostructured ZnO-based films for fluorescence biosensing applications. AB - The fluorescence-based sensing capability of ultrathin ZnO-SiO(2) nanoplatforms, deposited by an integrated approach of colloidal lithography and metal organic chemical vapor deposition, has been investigated upon adsorption of fluorescein labeled albumin, used as model analyte biomolecule. The protein immobilization process after spontaneous adsorption/desorption significantly enhances the green emission of the different ZnO-based films, as evidenced by scanning confocal microscopy, corresponding to a comparable protein coverage detected by X-ray photoelectron spectroscopy. Moreover, experiments of fluorescence recovery after photobleaching evidence that the protein lateral diffusion at the biointerface is affected by the chemical and/or topographical patterning of hybrid ZnO-SiO(2) surfaces. The used approach is very promising for biomolecular detection applications of these ZnO-SiO(2) nanoplatforms, by simple sizing of the 2D vs. 3D patterning design, which in turn is accomplished by the fine tuning of the integrated colloidal lithography-chemical vapor deposition processes. PMID- 21978403 TI - Mechanism of structural networking in hydrogels based on silicon and titanium glycerolates. AB - Formation of organic/inorganic hydrogels based on silicon- and titanium-glycerol precursors synthesized by transesterification of alkoxy derivatives in excess of glycerol was investigated. The precursors in excess of glycerol and obtained gels were studied by chemical and physical methods including gelation kinetics, IR spectroscopy, XRD, dynamic and electrophoretic light scattering, mechanical deformation, which disclosed the basic difference in the gelation mechanism and structure of network in the hydrogels. Due to this difference, the gelation time of silicon- and titanium-glycerol precursors depended on pH or electrolyte addition in an opposite way. In the wide pH range, silicon-glycerol hydrogel was a polymeric single-phase system formed by the polymeric network homogeneously swollen in liquid water/glycerol medium. Flory-Rehner theory applied to the elastic modulus of these gels gave 40-180 monomer base units in the subchains of the network depending on water content in the gel. The mechanism of networking was three-dimensional polycondensation promoted by the electrically charged functional groups attached to the flexible polymeric chains. Electrolyte solutions provided the gelation according to Hofmeister series. Titanium-glycerol hydrogels were heterogeneous colloid systems at pH>1.5 and single-phase polymeric gels at lower pH. Electrolyte solutions provided the gelation according to Schultze-Hardy rule. PMID- 21978404 TI - Kinetic study of the phase-transfer catalytic epoxidation of 1,4 bis(allyloxy)butane. AB - The epoxidation of 1,4-bis(allyloxy)butane (DiBan) with hydrogen peroxide as an oxidant in the presence of o-phosphoric acid and sodium tungstate as an epoxidation catalyst was carried out in an organic solvent/aqueous solution two phase medium. A few different phase-transfer catalysts were used in the process. The effect of the stirring speed, nature of solvent, the type of PT catalyst and molar ratio of H(2)O(2):DiBan, DiBan:Na(2)WO(4):H(3)PO(4) on the DiBan conversion as the function of time was studied. Based on the experimental results, a pseudo first-order expression for the reaction rate was applied and most efficient conditions epoxidation were developed. PMID- 21978406 TI - [Tracheobronchial amyloidosis: presentation of a case]. PMID- 21978405 TI - In vivo imaging of lymphocytes in the CNS reveals different behaviour of naive T cells in health and autoimmunity. AB - BACKGROUND: Two-photon laser scanning microscopy (TPLSM) has become a powerful tool in the visualization of immune cell dynamics and cellular communication within the complex biological networks of the inflamed central nervous system (CNS). Whereas many previous studies mainly focused on the role of effector or effector memory T cells, the role of naive T cells as possible key players in immune regulation directly in the CNS is still highly debated. METHODS: We applied ex vivo and intravital TPLSM to investigate migratory pathways of naive T cells in the inflamed and non-inflamed CNS. MACS-sorted naive CD4+ T cells were either applied on healthy CNS slices or intravenously injected into RAG1 -/- mice, which were affected by experimental autoimmune encephalomyelitis (EAE). We further checked for the generation of second harmonic generation (SHG) signals produced by extracellular matrix (ECM) structures. RESULTS: By applying TPLSM on living brain slices we could show that the migratory capacity of activated CD4+ T cells is not strongly influenced by antigen specificity and is independent of regulatory or effector T cell phenotype. Naive T cells, however, cannot find sufficient migratory signals in healthy, non-inflamed CNS parenchyma since they only showed stationary behaviour in this context. This is in contrast to the high motility of naive CD4+ T cells in lymphoid organs. We observed a highly motile migration pattern for naive T cells as compared to effector CD4+ T cells in inflamed brain tissue of living EAE-affected mice. Interestingly, in the inflamed CNS we could detect reticular structures by their SHG signal which partially co localises with naive CD4+ T cell tracks. CONCLUSIONS: The activation status rather than antigen specificity or regulatory phenotype is the central requirement for CD4+ T cell migration within healthy CNS tissue. However, under inflammatory conditions naive CD4+ T cells can get access to CNS parenchyma and partially migrate along inflammation-induced extracellular SHG structures, which are similar to those seen in lymphoid organs. These SHG structures apparently provide essential migratory signals for naive CD4+ T cells within the diseased CNS. PMID- 21978407 TI - [Cardiac arrest: radiological findings in abdominal computed tomography]. PMID- 21978408 TI - [Radiological diagnostic approach to idiopathic interstitial pneumonias: findings in high resolution computed tomography]. AB - A review is presented on the histological and radiological findings in idiopathic interstitial pneumonias, which are included among the diffuse parenchymal lung diseases. Although they may affect other compartments, the lung interstitium is the initial substrate of the parenchymal lesion due to different patterns of inflammation and fibrosis. The current classification, proposed in 2002 as an international multidisciplinary consensus document promoted by the American Thoracic Society and the European Respiratory Society, includes 7 conditions. Based on histological criteria, each histological pattern is associated with an image pattern. They are a group of conditions of unknown origin with common characteristics and differential features that enable them to be individualised as diseases with a different prognosis and treatment. They are rare as idiopathic forms, but share a morphological substrate with other more common diseases of unknown cause, which means they have to be excluded to reach a definitive diagnosis. For this reason it is important that the radiologist is familiar with their characteristic imaging findings. PMID- 21978409 TI - Recruiting South Asians to a lifestyle intervention trial: experiences and lessons from PODOSA (Prevention of Diabetes & Obesity in South Asians). AB - BACKGROUND: Despite the growing emphasis on the inclusion of ethnic minority patients in research, there is little published on the recruitment of these populations especially to randomised, community based, lifestyle intervention trials in the UK. METHODS: We share our experience of recruitment to screening in the PODOSA (Prevention of Diabetes and Obesity in South Asians) trial, which screened 1319 recruits (target 1800) for trial eligibility. A multi-pronged recruitment approach was used. Enrolment via the National Health Service included direct referrals from health care professionals and written invitations via general practices. Recruitment within the community was carried out by both the research team and through our partnerships with local South Asian groups and organisations. Participants were encouraged to refer friends and family throughout the recruitment period. RESULTS: Health care professionals referred only 55 potential participants. The response to written invitations via general practitioners was 5.2%, lower than reported in other general populations. Community orientated, personal approaches for recruitment were comparatively effective yielding 1728 referrals (82%) to the screening stage. CONCLUSIONS: The PODOSA experience shows that a community orientated, personal approach for recruiting South Asian ethnic minority populations can be successful in a trial setting. We recommend that consideration is given to cover recruitment costs associated with community engagement and other personalised approaches. Researchers should consider prioritising approaches that minimise interference with professionals' work and, particularly in the current economic climate, keep costs to a minimum. The lessons learned in PODOSA should contribute to future community based trials in South Asians. TRIAL REGISTRATION: Current Controlled Trials ISRCTN25729565. PMID- 21978412 TI - Effect of production system on carcass measurements and meat quality of Kivircik lambs. AB - Effect of production system on carcass and meat quality was investigated in four groups of lambs: i. W-C lambs were weaned between 45 and 60 days of age and then were fattened with concentrate feed until slaughter; ii. W-G-S lambs were weaned and then taken to pasture and wheat stubble; iii. UW-C lambs were fattened with concentrate feed and they suckled their dams until slaughter; iv. UW-G lambs were kept with their dams and were taken to pasture in the day-time. Hot carcass weight was 13.62, 12.52, 14.37 and 13.88 kg (P < 0.001), and dressing percentage was 55.24, 51.77, 57.83 and 55.38% (P < 0.001), for W-C, W-G-S, UW-C and UW-G lambs, respectively. Ultimate meat pH was higher in W-G-S lambs than lambs from W C and UW-C systems (P < 0.05). W-G-S lambs had higher shear force value in longissimus dorsi muscle (P < 0.05) and lower meat lightness (P < 0.001) than those of other systems. Panellists gave the lowest sensory scores, except juiciness, to meat of W-G-S lambs. PMID- 21978410 TI - Comparative analysis of the human hepatic and adipose tissue transcriptomes during LPS-induced inflammation leads to the identification of differential biological pathways and candidate biomarkers. AB - BACKGROUND: Insulin resistance (IR) is accompanied by chronic low grade systemic inflammation, obesity, and deregulation of total body energy homeostasis. We induced inflammation in adipose and liver tissues in vitro in order to mimic inflammation in vivo with the aim to identify tissue-specific processes implicated in IR and to find biomarkers indicative for tissue-specific IR. METHODS: Human adipose and liver tissues were cultured in the absence or presence of LPS and DNA Microarray Technology was applied for their transcriptome analysis. Gene Ontology (GO), gene functional analysis, and prediction of genes encoding for secretome were performed using publicly available bioinformatics tools (DAVID, STRING, SecretomeP). The transcriptome data were validated by proteomics analysis of the inflamed adipose tissue secretome. RESULTS: LPS treatment significantly affected 667 and 483 genes in adipose and liver tissues respectively. The GO analysis revealed that during inflammation adipose tissue, compared to liver tissue, had more significantly upregulated genes, GO terms, and functional clusters related to inflammation and angiogenesis. The secretome prediction led to identification of 399 and 236 genes in adipose and liver tissue respectively. The secretomes of both tissues shared 66 genes and the remaining genes were the differential candidate biomarkers indicative for inflamed adipose or liver tissue. The transcriptome data of the inflamed adipose tissue secretome showed excellent correlation with the proteomics data. CONCLUSIONS: The higher number of altered proinflammatory genes, GO processes, and genes encoding for secretome during inflammation in adipose tissue compared to liver tissue, suggests that adipose tissue is the major organ contributing to the development of systemic inflammation observed in IR. The identified tissue-specific functional clusters and biomarkers might be used in a strategy for the development of tissue-targeted treatment of insulin resistance in patients. PMID- 21978413 TI - Opinion on opinions about geriatric assessment. PMID- 21978414 TI - Empirical antibiotic therapy (ABT) of lower respiratory tract infections (LRTI) in the elderly: application of artificial neural network (ANN). Preliminary results. AB - LRTI are among the most common diseases in developed countries, including chronic obstructive pulmonary disease (COPD), one of the most frequent conditions. Their treatment in general practice is often unsuccessful and this increases hospital admissions. We know, bacterial infections in the elderly show a higher morbidity and mortality, either for more severe symptoms, than in younger adults, or because the causing agent often remains unknown. The need for a quick initiation of ABT often requires to chose on empirical grounds. To date there are no official guidelines for empirical ABT of COPD exacerbations, but only heterogeneous and often conflicting recommendations exist. The aim of our study was to identify a tool to guide the choice of the most effective empirical ABT when symptoms are acute and bacteriological tests cannot be performed. We used an ANN to study 117 patients aged between 55 and 97 years (mean 81.5 +/- 8.7 years) (+/- S.D.), admitted with a diagnosis of pneumonia, COPD exacerbation or pneumonia with respiratory failure. We registered symptoms at onset and some individual variables such as age, sex, risk factors, comorbidity, current drug therapies. Then the ANN was applied to choose ABT in 20 patients versus 20 subjects whose therapy was chosen by the physicians, comparing these groups for therapy's efficacy, mean durations of therapy and hospitalization (H). In the learning phase, the ANN could predict the resolution index 99.05% of the time (i.e., 104 times) with a +/- S.D. = 0.23. After the training, during the test phase, the network predicted the resolution index 91.67% of the time (i.e., 11 times) with a +/- S.D. = 0.54, thus proving the validity of the relations identified during the learning phase. Preliminary results of the application of our tool, show the ANN allowed us to greatly reduce the duration of the ABT and subsequently of the H. Based on preliminary results, we assume that the use of ANN can make a valuable contribution in the choice of empirical ABT in the course of acute lung diseases in elderly. PMID- 21978415 TI - Unrecognized vertebral body fractures (VBFs) in chest radiographic reports in Taiwan: a hospital-based study. AB - Osteoporosis and its associated fragility fractures greatly impact the health care system. VBF can be inadvertently overlooked on radiological examinations, which may delay diagnosis and treatment of osteoporosis. This hospital-based study evaluated chest radiographs to determine the prevalence rate of unrecognized VBF. Digitalized chest radiographs stored in the Taipei Veterans General Hospital Radiology Information System (TVGHRIS) were retrieved for study. One month of image data from 2009 was randomly obtained. All patients were over 55 years of age. Posterior-anterior (PA) and lateral chest radiographs were available for all patients. All selected chest radiographs were reviewed by two radiologists who were blinded to the official reports. Comparisons between official reports and the reference reports determined the prevalence of unrecognized VBF. Chest radiographs from 1655 patients (mean age 71.9 +/- 10.4 years, 63.9% male) were reviewed. The prevalence of recognized VBF was significantly higher in consensus reports compared to the official reports (23.0% vs. 4.8%, p<0.001). Overall, 79% of VBFs were undiagnosed. The prevalence of unrecognized VBFs was 18.2% (19.6% in men, 15.7% in women). VBFs in men were more likely to be unrecognized than women (19.6% vs. 15.7%, p=0.04). Adjusted for age, gender was not an independent risk factor for unrecognized VBF in logistic regression. In conclusion, the high rate of unrecognized VBF in a tertiary medical center in Taiwan highlights the need to improve radiographic recognition of VBF, which could aid early treatment of osteoporosis in older adults. PMID- 21978416 TI - Asymmetry assessment using cone beam CT. A Class I and Class II patient comparison. AB - OBJECTIVE: To estimate possible differences in skeletal asymmetry between patients with skeletal Class I and skeletal Class II relationships. MATERIALS AND METHODS: Cone beam computed tomography (CBCT) images were examined from 70 consecutive patients who presented for orthodontic care and fit the inclusion criteria. Asymmetry was quantified using an asymmetry index developed by Katsumata et al. Anatomic landmarks were defined and reference planes were established to determine the asymmetry of the landmarks using a constructed coordinate plane system. Thirty randomly selected patients were reanalyzed to assess the reliability of the method. RESULTS: Statistical analysis did not find any significant relationship between asymmetry and A-P skeletal relationship for any of the landmarks. Asymmetry index scores were reproducible within a certain range of agreement for each landmark. CONCLUSIONS: Based on this study, the discrepant jaw growth resulting in a Class II skeletal pattern results in no more skeletal asymmetry than Class I skeletal patterns. PMID- 21978417 TI - The relationship between base dimensions, force to failure, and shear bond strengths of bondable molar tubes. AB - OBJECTIVES: To compare forces versus failure and shear bond strengths, and to explore their association with the base dimensions of four currently available bondable molar tubes. MATERIALS AND METHODS: Tubes were bonded to hydroxyapatite discs using a conventional light-cured adhesive and were tested to shear failure with the Instron Universal testing machine. Results were analyzed using the Kruskal-Wallis test and regression and survival analyses. RESULTS: No statistical difference was observed between the four groups globally in terms of force to failure (P = .059) and bond strength (P = .179). However, regression analysis showed that each 1 mm(2) increase in base surface area required an additional force of 3.11 N to debond the tube. Survival analysis showed that the tube with the greatest base dimensions had the best survival with increasing force to failure. CONCLUSIONS: Although a relationship was demonstrated between force to failure and base surface area, it was not a simple one. No statistically significant relationship was found between bond strength and base surface area. PMID- 21978419 TI - EGF enhances the migration of cancer cells by up-regulation of TRPM7. AB - Ion channels involved in the migration of tumor cells that is required for their invasion and metastasis. In this paper, we describe the interaction of TRPM7 channel and epidermal growth factor (EGF), an important player in cancer development in the migration of lung cancer cells. The TRPM7 currents in A549 cells were first characterized by means of electrophysiology, pharmacology and RNA interference. Removing Ca(2+) from the extracellular solution not only potentiated a large inward current, but also abolished the outward rectification. 200MUM 2-APB inhibited the outward and the inward TRPM7 currents and at the same time restored the property of outward rectification. EGF greatly enhanced the migration of A549 cells, and also markedly up-regulated the membrane protein expression of TRPM7 and the amplitude of TRPM7 currents. Depressing the function of TRPM7 with RNA interference or pharmacological agents not only reversed the EGF-enhanced migration of A549 cells but also inhibited the basal migration of A549 cells in the absence of EGF. Thus it seems that TRPM7 plays a pivotal role in the migration of A549 cells induced by EGF and thus could be a potential therapeutic target in lung cancers. PMID- 21978420 TI - Tramadol for the treatment of premature ejaculation. PMID- 21978418 TI - Imaging of a glucose analog, calcium and NADH in neurons and astrocytes: dynamic responses to depolarization and sensitivity to pioglitazone. AB - Neuronal Ca(2+) dyshomeostasis associated with cognitive impairment and mediated by changes in several Ca(2+) sources has been seen in animal models of both aging and diabetes. In the periphery, dysregulation of intracellular Ca(2+) signals may contribute to the development of insulin resistance. In the brain, while it is well-established that type 2 diabetes mellitus is a risk factor for the development of dementia in the elderly, it is not clear whether Ca(2+) dysregulation might also affect insulin sensitivity and glucose utilization. Here we present a combination of imaging techniques testing the disappearance of the fluorescent glucose analog 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2 deoxyglucose (2-NBDG) as an indication of glycolytic activity in neurons and astrocytes. Our work shows that glucose utilization at rest is greater in neurons compared to astrocytes, and ceases upon activation in neurons with little change in astrocytes. Pretreatment of hippocampal cultures with pioglitazone, a drug used in the treatment of type 2 diabetes, significantly reduced glycolytic activity in neurons and enhanced it in astrocytes. This series of experiments, including Fura-2 and NADH imaging, provides results that are consistent with the idea that Ca(2+) levels may rapidly alter glycolytic activity, and that downstream events beyond Ca(2+) dysregulation with aging, may alter cellular metabolism in the brain. PMID- 21978421 TI - A new platform improving the ergonomics of laparoscopic surgery: initial clinical evaluation of the prototype. PMID- 21978422 TI - Incidence, prevention, and management of complications following percutaneous nephrolitholapaxy. AB - CONTEXT: Incidence, prevention, and management of complications of percutaneous nephrolitholapaxy (PNL) still lack consensus. OBJECTIVE: To review the epidemiology of complications and their prevention and management. EVIDENCE ACQUISITION: A literature review was performed using the PubMed database between 2001 and May 1, 2011, restricted to human species, adults, and the English language. The Medline search used a strategy including medical subject headings (MeSH) and free-text protocols with the keywords percutaneous, nephrolithotomy, PCNL, PNL, urolithiasis, complications, and Clavien, and the MeSH terms nephrostomy, percutaneous/adverse effects, and intraoperative complications or postoperative complications. EVIDENCE SYNTHESIS: Assessing the epidemiology of complications is difficult because definitions of complications and their management still lack consensus. For a reproducible quality assessment, data should be obtained in a standardized manner, allowing for comparison. An approach is the validated Dindo-modified Clavien system, which was originally reported by seven studies. No deviation from the normal postoperative course (Clavien 0) was observed in 76.7% of PNL procedures. Including deviations from the normal postoperative course without the need for pharmacologic treatment or interventions (Clavien 1) would add up to 88.1%. Clavien 2 complications including blood transfusion and parenteral nutrition occurred in 7%; Clavien 3 complications requiring intervention in 4.1.%; Clavien 4, life-threatening complications, in 0.6%; and Clavien 5, mortality, in 0.04%. High-quality data on complication management of rare but potentially debilitating complications are scarce and consist mainly of case reports. CONCLUSIONS: Complications after PNL can be kept to a minimum in experienced hands with the development of new techniques and improved technology. A modified procedure-specific Clavien classification should be established that would need to be validated in prospective trials. PMID- 21978423 TI - Enhanced anaerobic treatment of CSTR-digested effluent from chicken manure: The effect of ammonia inhibition. AB - The effect of ammonia inhibition was evaluated during the enhanced anaerobic treatment of digested effluent from a 700m(3) chicken-manure continuous stirred tank reactor (CSTR). A 12.3L internal circulation (IC) reactor inoculated with an anaerobic granular sludge and operated at 35+/-1 degrees C was employed for the investigation. With a corresponding organic loading rate of 1.5-3.5kg-COD/m(3)d over a hydraulic retention time of 1.5d, a maximum volumetric biogas production rate of 1.2m(3)/m(3)d and TCOD (total COD) removal efficiency ranging from 70% to 80% was achieved. However, the continual increase in the influent TAN content led to ammonia inhibition in the methanogenesis system. The SCOD/TAN (soluble COD/total ammonia nitrogen) ratio was presented to be the key controlling factor for the anaerobic treatment of semi-digested chicken manure, and further validation through shock loading and ammonia inhibition experiments was conducted. The threshold value of the SCOD/TAN ratio was determined to be 2.4 (corresponding to a TAN of 1250mg/L) at an influent pH of 8.5-9. PMID- 21978424 TI - Modelling of organic matter dynamics during the composting process. AB - Composting urban organic wastes enables the recycling of their organic fraction in agriculture. The objective of this new composting model was to gain a clearer understanding of the dynamics of organic fractions during composting and to predict the final quality of composts. Organic matter was split into different compartments according to its degradability. The nature and size of these compartments were studied using a biochemical fractionation method. The evolution of each compartment and the microbial biomass were simulated, as was the total organic carbon loss corresponding to organic carbon mineralisation into CO(2). Twelve composting experiments from different feedstocks were used to calibrate and validate our model. We obtained a unique set of estimated parameters. Good agreement was achieved between the simulated and experimental results that described the evolution of different organic fractions, with the exception of some compost because of a poor simulation of the cellulosic and soluble pools. The degradation rate of the cellulosic fraction appeared to be highly variable and dependent on the origin of the feedstocks. The initial soluble fraction could contain some degradable and recalcitrant elements that are not easily accessible experimentally. PMID- 21978425 TI - Comparison of batch leaching tests and influence of pH on the release of metals from construction and demolition wastes. AB - Construction and demolition wastes are suitable for use in road construction. However, leaching characterization of recycled materials is required to determine their pollutant potential and the consequence of their application in different scenarios. The motivation of this paper is derived from the increasing use of different leaching test methods. In Europe, the confusion resulting from the wide variety of tests used to evaluate environmental properties of construction materials implies that an evaluation of the current practices and the attempt to consolidate the approaches are required. Two equilibrium-based leaching tests (the Dutch test and the European standard) were conducted to assess the environmental impact of four recycled aggregates. Three natural limestone aggregates were used as controls. Both tests measure the potential release of hazardous elements under extreme conditions using different leaching parameters (L/S ratio, pH value and contact time). The results proved that pH is the most relevant factor on the assessment of the differences between leaching methods due to its strong control on the pollutant release. To classify the materials according to their environmental effects, the concentration limit values of the metals imposed by Council Decision 2003/33/EC were used as a reference. The comparison allowed the classification of the recycled aggregates as inert wastes, with the exception of the MR-2 aggregate, which was classified as non-hazardous material. PMID- 21978426 TI - Optimal combination of immunohistochemical markers for subclassification of non small cell lung carcinomas: A tissue microarray study of poorly differentiated areas. AB - BACKGROUND: Recently, studies have been reported on the optimal immunohistochemical markers for subclassification of non-small cell lung carcinoma (NSCLC). The main pitfall in subclassification of NSCLC is small specimen with poorly differentiated area. In this study, we added newly proposed markers (e.g., napsin A, SOX2) to conventional markers (p63, TTF-1, CK5/6, and CK7) and evaluated optimal combination for subtyping of NSCLC, primarily focusing on the poorly differentiated area. METHODS: Eighty two resected NSCLCs with poorly differentiated areas were classified based on histologic findings. After histologic review, only poorly differentiated areas were selected and tissue microarrays were constructed to simulate small biopsy conditions. A total of 36 adenocarcinomas (ADCs), 38 squamous cell carcinomas (SQCCs), and 8 large cell carcinomas were included. All specimens were stained with TTF-1, napsin A, CK7, p63, CK5/6, and SOX2. RESULTS: With respect to ADC, TTF-1 was positive in 19 of 36 cases (53%) and napsin A was in 25 of 36 (69%). Both markers were specific for ADC (100% and 98%, respectively). With TTF-1 and napsin A in combination, sensitivity increased to 75%. CK7 was sensitive (92%) but not specific marker (76%) for ADC. With respect to SQCC, p63 was positive in 35 of 38 cases (92%) and CK5/6 was in 23 (61%). Both markers were specific for SQCC (both 93%). With p63 and CK5/6 in combination, sensitivity increased slightly to 95%, but specificity was lower at 91%. SOX2 was specific (100%) but not sensitive marker (53%) for SQCC. Combinations did not substantially increase the diagnostic performance. CONCLUSION: A simple panel of napsin A, TTF-1, and p63 can be sufficient to reliably subclassify poorly differentiated areas of NSCLC. PMID- 21978427 TI - Clinical and dimensional characteristics of euthymic bipolar patients with or without suicidal behavior. AB - BACKGROUND: The clinical and dimensional features associated with suicidal behaviour in bipolar patients during euthymic states are not well characterised. METHODS: In a sample of 652 euthymic bipolar patients, we assessed clinical features with the Diagnostic Interview for Genetics Studies (DIGS) and dimensional characteristics with questionnaires measuring impulsivity/hostility and affective lability/intensity. Bipolar patients with and without suicidal behaviour were compared for these clinical and dimensional variables. RESULTS: Of the 652 subjects, 42.9% had experienced at least one suicide attempt. Lifetime history of suicidal behaviour was associated with being a woman, a history of head injury, tobacco misuse and indicators of severity of bipolar disorder including early age at onset, high number of depressive episodes, positive history of rapid cycling, alcohol misuse and social phobia. Indirect hostility and irritability were dimensional characteristics associated with suicidal behaviour in bipolar patients, whereas impulsivity and affective lability/intensity were not associated with suicidal behaviour. LIMITATIONS: This study had a retrospective design with no replication sample. CONCLUSIONS: Bipolar patients with earlier onset, mood instability (large number of depressive episodes, rapid cycling) and/or particular addictive and anxiety comorbid disorders might be at high risk of suicidal behaviour. In addition, hostility dimensions (indirect hostility and irritability), may be trait components associated with suicidal behaviour in euthymic bipolar patients. PMID- 21978428 TI - A comparative clinical evaluation of the outcome of patients treated for bilateral fracture of the mandibular condyles. AB - AIM: To compare open reduction and internal fixation (ORIF) with closed treatment and maxillomandibular fixation (CRMMF) for management of bilateral subcondylar fractures of the mandible. PATIENTS AND METHODS: This study involved a retrospective analysis of bilateral subcondylar fractures of the mandible treated at Government Dental College, Rohtak from 2007 to 2010. Data were collected by a review of pertinent inpatient and outpatient clinic records, and radiographic results. Patients were followed up weekly for 4 weeks and then at 2, 3 and 6 months after surgery. At these visits, careful attention was paid to clinical parameters included mouth opening, protrusion, laterotrusion, deviation on mouth opening and occlusion. RESULTS: The patient sample ranged in age from 19 to 55 years, with an average age of 28.2 years. In total, 44 patients with 88 mandibular subcondylar fractures were included in the study. Out of these, 20 patients were managed by closed treatment and 24 by ORIF of the subcondylar fractures (19 unilateral and 5 bilateral). Regarding mouth opening/lateral excursion/protrusion, significant (p=0.00) differences were observed between both groups (open 37.6/11.5/5.9 mm versus closed 31.5/7.8/3.1mm). The visual analogue scoring revealed significant (p=0.00) difference with less pain in the operative treatment group (1.3 open versus 7.2 closed). Statistically significant difference was found between two groups for occlusion (p=0.00). CONCLUSION: The current retrospective study shows that operative treatment was superior in all objective and subjective functional parameters. It is concluded that if either of the condyles is displaced ORIF is the most satisfactory method of treatment. PMID- 21978429 TI - Future of surgery: accountable care organizations and the end of private practice? PMID- 21978430 TI - HLA-DRB1 shared epitope genotyping using the revised classification and its association with circulating autoantibodies, acute phase reactants, cytokines and clinical indices of disease activity in a cohort of South African rheumatoid arthritis patients. AB - INTRODUCTION: The revised shared epitope (SE) concept in rheumatoid arthritis (RA) is based on the presence (S) or absence (X) of the SE RAA amino acid motif at positions 72 to 74 of the third hypervariable region of the various human leucocyte antigen (HLA)-DRB1 alleles. The purpose of this study was to investigate SE subtypes on the basis of the American College of Rheumatology 1987 revised criteria for the classification of RA in a cohort of South African RA patients (n = 143) and their association with clinical and circulating biomarkers of disease activity (autoantibodies, acute phase reactants and cytokines). METHODS: Genomic DNA was analysed using high-resolution recombinant sequence specific oligonucleotide PCR typing of the HLA-DRB1 allele. Subtypes of the SE were classified according to the amino acids at positions 72 to 74 for the RAA sequence, and further sub-divided according to the amino acids at positions 70 and 71, which either contribute to (S2, S3P), or negate (S1, S3D) RA susceptibility. Disease activity was assessed on the basis of (1) Disease Activity Score in 28 joints using C-reactive protein (CRP), (2) rheumatoid factor (RF), (3) CRP and (4) serum amyloid A by nephelometry, anticyclic citrullinated peptide antibodies (aCCP) by an immunofluorometric procedure, and cytokines by multiplex bead array technology. RESULTS: Of the 143 RA patients, 81 (57%) were homozygous (SS) and 50 (35%) were heterozygous (SX) for the SE alleles with significant overexpression of S2 and S3P (respective odds ratios (ORs) 5.3 and 5.8; P < 0.0001), and 12 (8%) were classified as no SE allele (XX). Both the SS and SX groups showed a strong association with aCCP positivity (OR = 10.2 and P = 0.0010, OR = 9.2 and P = 0.0028, respectively) relative to the XX group. Clinical scores and concentrations of the other biomarkers of disease activity (RF, CRP and T helper cell type 1 (Th1), Th2, macrophage and fibroblast cytokines) were also generally higher in the SS group than in the SX and XX groups. CONCLUSIONS: RA susceptibility alleles investigated according to revised criteria for the classification of RA were significantly increased in South African RA patients and strongly associated with aCCP in particular as well as with circulating cytokines and disease severity. PMID- 21978431 TI - Resorption and remodeling of hydroxyapatite-poly-L-lactic acid composite anterior cruciate ligament interference screws. AB - PURPOSE: The purpose of this study was to evaluate the progression of hydroxyapatite-poly-L-lactic acid (HA-PLLA) interference screw resorption and remodeling in patients after anterior cruciate ligament (ACL) reconstruction. METHODS: Sixty-five patients undergoing ACL reconstruction with patellar tendon autograft or allograft fixed at both the femur and tibia with HA-PLLA screws were evaluated. We evaluated 10 patients each at 2, 3, and 4 years postoperatively, whereas 35 patients were evaluated at 5 years postoperatively. In all patients a physical examination was performed and functional outcome scores and computed tomography (CT) analysis were obtained at follow-up. RESULTS: Screw tract densities determined by CT at 5 years postoperatively were higher than muscle and were similar to the surrounding bone. At 4 years, 80% to 90% of screws were completely resorbed. At 5-year follow-up, 29% of patients showed complete ossification of the screw tract in the femur versus 34% in the tibia. There was no tunnel widening or sclerosis noted. Subjective and objective clinical results remained high throughout the study period. CONCLUSIONS: The HA-PLLA interference screws are slowly resorbed over time, and the majority are completely resorbed between 3 and 4 years after ACL reconstruction with patellar tendon autograft or allograft. Osteoconductivity and remodeling were confirmed by CT scans, and no tunnel widening, sclerosis, cysts, or inflammatory changes were noted. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 21978432 TI - A prospective, randomized evaluation of acellular human dermal matrix augmentation for arthroscopic rotator cuff repair. AB - PURPOSE: To prospectively evaluate the safety and effectiveness of arthroscopic acellular human dermal matrix augmentation of large rotator cuff tear repairs. METHODS: A prospective, institutional review board-approved, multicenter series of patients undergoing arthroscopic repair of 2-tendon rotator cuff tears measuring greater than 3 cm were randomized by sealed envelopes opened at the time of surgery to arthroscopic single-row rotator cuff repair with GraftJacket acellular human dermal matrix (Wright Medical Technology, Arlington, TN) augmentation (group 1) or without augmentation (group 2). Preoperative and postoperative functional outcome assessments were obtained by use of the American Shoulder and Elbow Surgeons (ASES), Constant, and University of California, Los Angeles scales. Gadolinium-enhanced magnetic resonance imaging (MRI) evaluation of these repairs was obtained at a mean of 14.5 months (range, 12 to 24 months). Adverse events were recorded. RESULTS: There were 22 patients in group 1 and 20 in group 2 with a mean age of 56 years. The mean follow-up was 24 months (range, 12 to 38 months). The ASES score improved from 48.5 to 98.9 in group 1 and from 46.0 to 94.8 in group 2. The scores in group 1 were statistically better than those in group 2 (P = .035). The Constant score improved from 41.0 to 91.9 in group 1 and from 45.8 to 85.3 in group 2. The scores in group 1 were statistically better than those in group 2 (P = .008). The University of California, Los Angeles score improved from 13.3 to 28.2 in group 1 and from 15.9 to 28.3 in group 2 (P = .43). Gadolinium-enhanced MRI scans showed intact cuffs in 85% of repairs in group 1 and 40% in group 2 (P < .01). No adverse events were attributed to the presence of the matrix grafts. CONCLUSIONS: Acellular human dermal matrix augmentation of large (>3 cm) cuff tears involving 2 tendons showed better ASES and Constant scores and more frequent intact cuffs as determined by gadolinium-enhanced MRI. Intact repairs were found in 85% of the augmented group and 40% of the nonaugmented group (P < .01). No adverse events related to the acellular human dermal matrix were observed. LEVEL OF EVIDENCE: Level II, lesser quality randomized controlled trial. PMID- 21978433 TI - Two-year outcomes of open shoulder anterior capsular reconstruction for instability from severe capsular deficiency. AB - PURPOSE: To document outcomes after anterior capsulolabral reconstruction for recurrent shoulder instability in 15 patients (20 shoulders) who have had multiple failed stabilizations or collagen disorders. METHODS: Twenty shoulders with recurrent instability underwent revision stabilization with allograft reconstruction of anterior capsulolabral structures, which re-creates the labrum and capsular ligaments. The patients comprised 3 men and 12 women (mean age, 26 years [range, 18 to 38 years]) in whom multiple prior repairs failed and who had disability from continued pain and instability. Patients could choose to undergo either arthrodesis or salvage allograft reconstruction or to live with permanent disability. Of the patients, 5 had Ehlers-Danlos syndrome whereas 10 had hyperlaxity syndromes without genetic confirmation. Failure was defined as further instability surgery. Pain, shoulder function, instability (dislocations/subluxation), and American Shoulder and Elbow Surgeons scores were documented. RESULTS: At follow-up, 9 of 20 shoulders (45%) remained stable. Recurrent instability was reported in 5 shoulders (25%), but the patients chose not to undergo further surgery. In the 14 shoulders without further stabilization (nonfailures), the mean American Shoulder and Elbow Surgeons score increased 43 points at a mean of 3.8 years (range, 2 to 6 years) postoperatively (P < .05). Mean satisfaction with outcome in nonfailures was 7 of 10 points (range, 1 to 10). Six shoulders failed by progressing to instability surgery at a mean of 8.6 months (range, 2.8 to 24 months). In the 6 shoulders that failed, the mean number of prior surgeries was 8 (range, 3 to 15) compared with a mean of 4 prior surgeries (range, 1 to 16) for the 9 nonfailures. CONCLUSIONS: Treating patients in whom multiple stabilizations have failed remains challenging. In our series 9 shoulders (45%) remained completely stable at 3.8 years. Recurrent instability (3 reinjuries) requiring further stabilization occurred in 6 (30%). Subsequent treatment for non-instability reasons was performed in 3 (15%). Instability was reported but revision surgery was not performed in 5 (25%). In 8 nonfailures (64%), the patients were highly satisfied with their surgical outcomes. Our results support this salvage procedure as a viable alternative to arthrodesis in young patients with end-stage shoulder instability or collagen disorders. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 21978434 TI - Bone marrow-derived mesenchymal stem cells obtained during arthroscopic rotator cuff repair surgery show potential for tendon cell differentiation after treatment with insulin. AB - PURPOSE: The purpose of this study was to determine whether a one-time physiologic dose of insulin when compared with the growth factors insulin-like growth factor 1, beta-fibroblastic growth factor, and growth differentiation factor 5 is capable of differentiating bone marrow-derived mesenchymal stem cells (MSCs) into tendon. METHODS: Eleven patients undergoing arthroscopic rotator cuff repair consented to undergo aspiration of bone marrow. A dose-response curve was calculated to determine the optimal dose of insulin needed to differentiate MSCs into tendon. After purification of bone marrow in the operating room, MSCs were exposed to either insulin or tendon-inducing growth factors or were left untreated to serve as a control. The potential for MSCs in each of these groups to differentiate into tendon was evaluated with a multistep process that included determination of the genetic upregulation for tendon-specific proteins, confirmation that the levels of these proteins were actually increased, staining of the MSCs with antibodies for these proteins to ensure that they were expressed on the cell surface, and finally, evaluation of cell morphology to verify the MSCs' tendon-like appearance. RESULTS: MSCs treated with insulin showed increased gene expression of tendon-specific markers (P < .05), increased content of tendon specific proteins (P < .05), and increased receptors on the cell surface (P < .05) compared with control cells. Histologic analysis showed a tendon-like appearance compared with the control cells. CONCLUSIONS: Bone marrow-derived MSCs treated with a single physiologic dose of insulin differentiated into cells with characteristics consistent with tendon. CLINICAL RELEVANCE: The potential for MSCs to differentiate into tendon after a 1-time dose of insulin may assist in developing practical biologic options for augmentation of rotator cuff repairs. PMID- 21978435 TI - Commentary to "A standardized classification of hypospadias". PMID- 21978436 TI - The DNA damage checkpoint allows recombination between divergent DNA sequences in budding yeast. AB - In the early steps of homologous recombination, single-stranded DNA (ssDNA) from a broken chromosome invades homologous sequence located in a sister or homolog donor. In genomes that contain numerous repetitive DNA elements or gene paralogs, recombination can potentially occur between non-allelic/divergent (homeologous) sequences that share sequence identity. Such recombination events can lead to lethal chromosomal deletions or rearrangements. However, homeologous recombination events can be suppressed through rejection mechanisms that involve recognition of DNA mismatches in heteroduplex DNA by mismatch repair factors, followed by active unwinding of the heteroduplex DNA by helicases. Because factors required for heteroduplex rejection are hypothesized to be targets and/or effectors of the DNA damage response (DDR), a cell cycle control mechanism that ensures timely and efficient repair, we tested whether the DDR, and more specifically, the RAD9 gene, had a role in regulating rejection. We performed these studies using a DNA repair assay that measures repair by single-strand annealing (SSA) of a double-strand break (DSB) using homeologous DNA templates. We found that repair of homeologous DNA sequences, but not identical sequences, induced a RAD9-dependent cell cycle delay in the G2 stage of the cell cycle. Repair through a divergent DNA template occurred more frequently in RAD9 compared to rad9Delta strains. However, repair in rad9Delta mutants could be restored to wild-type levels if a G2 delay was induced by nocodazole. These results suggest that cell cycle arrest induced by the Rad9-dependent DDR allows repair between divergent DNA sequences despite the potential for creating deleterious genome rearrangements, and illustrates the importance of additional cellular mechanisms that act to suppress recombination between divergent DNA sequences. PMID- 21978437 TI - Effects of solvents on in vitro potencies of platinum compounds. PMID- 21978439 TI - Cirrhosis and constitutional telomerase mutations. AB - There is currently a growing body of evidence supporting the role of a genetic predisposition in cirrhosis development. Given that telomere shortening has been associated with fibrosis progression, Calado et al. and Hartmann et al. recently focussed on telomerase gene mutations in human cirrhosis. PMID- 21978438 TI - New pathophysiological concepts underlying pathogenesis of pigment gallstones. AB - Pigment gallstones, which are much less frequent than cholesterol stones, are classified descriptively as "black" or "brown". They are composed mostly of calcium hydrogen bilirubinate, Ca(HUCB)(2), which is polymerized and oxidized in "black" stones but remains unpolymerized in "brown" stones. Black stones form in sterile gallbladder bile but brown stones form secondary to stasis and anaerobic bacterial infection in any part of the biliary tree, including the gallbladder. Other calcium salts coprecipitate in both stone types; crystalline calcium phosphate and/or carbonate in the case of "black" stones and amorphous calcium salts of long chain saturated fatty acids ("soaps") in the case of "brown" stones. Cholesterol is present in variable proportions in "brown" more than "black" stones and in the latter, the bile sterol may be totally absent. The "scaffolding" of both stone types is a mixed mucin glycoprotein matrix secreted by epithelial cells lining the biliary tree. The critical pathophysiological prerequisite for "black" stone formation is "hyperbilirubinbilia" (biliary hypersecretion of bilirubin conjugates). It is due principally to hemolysis, ineffective erythropoiesis, or pathologic enterohepatic cycling of unconjugated bilirubin. Endogenous biliary beta-glucuronidase hydrolysis of bilirubin conjugates in gallbladder bile provides HUCB(-) molecules that precipitate as insoluble salts with ionized Ca. Putatively, reactive oxygen species secreted by an inflamed gallbladder mucosa are responsible for transforming the initial soft yellow precipitates into hard black [Ca(HUCB)(2)](n) polymers. Despite "brown" gallstones being soft and amenable to mechanical removal, chronic anaerobic infection of the biliary tree is often markedly resistant to eradication. PMID- 21978440 TI - Perihilar cholangiocarcinoma, the need for a new staging system. AB - DeOliveira et al. have recently proposed a new staging system for perihilar cholangiocarcinoma that aims at standardizing reports on this disease. Such a tool is currently needed not only to allow comparisons of studies among centres but also over time. Data integration could in turn provide relevant information regarding resectability and prognosis of this rare cancer. PMID- 21978441 TI - Letter from the editors: image perception in nuclear medicine. PMID- 21978442 TI - Guest editorial: perception--the invisible element. PMID- 21978443 TI - The role of perception in imaging: past and future. AB - The accurate and efficient interpretation of medical images relies on a host of factors. Clearly the technologies and methods used to acquire, process, transmit, store, and display the image and associated data are critical, but they are only one-half of the equation. In the end, the final diagnostic interpretation and recommendations for further action lie with the clinician. Ideally we would like to believe that all decisions rendered by competent clinicians are correct, but the interpretation task is not always easy or black and white. Thus, decisions are not always absolutely conclusive, are often formulated with plausible alternatives, and errors in interpretation can and do occur regularly. The discipline of medical image perception seeks an improved understanding of the perceptual factors that underlie the creation and interpretation of medical images, with the belief that improved diagnostic performance with the use of imaging devices can be achieved by the development of systems that are optimized for the interpretation of visual diagnostic information. Perception research can identify specific reasons for missed diagnoses, thereby helping to train physicians and eliminate diagnostic errors, and clarifying situations in which errors are a consequence of fundamentally ambiguous information rather than poor reader performance. The goal of this article is to provide a short review of the history of the discipline of medical image perception, highlight key research areas, and provide a look toward the future regarding the role that medical image perception research will continue to fill as imaging technology in medicine advances and develops. PMID- 21978445 TI - Visual perception studies and observer models in medical imaging. AB - Most academic radiologists will be familiar with receiver operating characteristic (ROC) studies. Fundamental studies of human observer performance are now usually performed by forced-choice methods. Both methods are based on signal detection theory. The ROC method gives an operating curve of true-positive versus false-positive probabilities. The area under the curve, A(Z), can be used a summary performance measure. In the forced-choice method, observers are given 2 or more images with one containing the signal. The observer's task is to select the option most likely to contain the signal. The percentage of correct responses, PC, is a summary performance measure. Precise comparison of the 2 methods is limited to very controlled experiments in which signals (simulated lesions for example) are carefully designed and detection or discrimination is limited by true random noise. Under these conditions, theory predicts a simple relationship between summary measures and human results are consistent with theory. There will be a description of forced-choice experimental methods and data analysis. There has also been considerable work on development of theoretic observer models. Human experiment results have used to evaluate the models. Models that correlate well with human performance in turn can be used for preliminary design of new imaging systems and for selection of image quality metrics for comparing equipment performance, this article will provide a summary of work during the last 30 years on evaluating human signal detection capabilities, observer models and image quality metrics. PMID- 21978444 TI - New developments in observer performance methodology in medical imaging. AB - A common task in medical imaging is assessing whether a new imaging system, or a variant of an existing one, is an improvement over an existing imaging technology. Imaging systems are generally quite complex, consisting of several components-for example, image acquisition hardware, image processing and display hardware and software, and image interpretation by radiologists- each of which can affect performance. Although it may appear odd to include the radiologist as a "component" of the imaging chain, because the radiologist's decision determines subsequent patient care, the effect of the human interpretation has to be included. Physical measurements such as modulation transfer function, signal-to noise ratio, are useful for characterizing the nonhuman parts of the imaging chain under idealized and often unrealistic conditions, such as uniform background phantoms and target objects with sharp edges. Measuring the performance of the entire imaging chain, including the radiologist, and using real clinical images requires different methods that fall under the rubric of observer performance methods or "ROC" analysis, that involve collecting rating data on images. The purpose of this work is to review recent developments in this field, particularly with respect to the free-response method, where location information is also collected. PMID- 21978446 TI - Synthetic positron emission tomography-computed tomography images for use in perceptual studies. AB - To better understand fundamental issues, perception studies of the fusion display would best be performed with a panel of lesions of variable location, size, intensity, and background. There are compelling reasons to use synthetic images that contain artificial lesions for perception research. A consideration of how to obtain this panel of lesions is the nucleus of the present review. This article is a conjoint effort of 3 groups that have joined together to review results from work that they and others have performed. The techniques we review include (1) substitution of lesions into a preexisting image matrix (either using actual prior patient-derived lesions or mathematically modeled artificial lesions), (2) addition of images (either in the attenuation-corrected image space or at an earlier stage before image reconstruction), and (3) simulation of the entire patient image. A judicious combination of the techniques discussed in this review may represent the most efficient pathway of simulating statistically varied but realistic appearing lesions. PMID- 21978447 TI - Computer-aided diagnosis and artificial intelligence in clinical imaging. AB - Computer-aided diagnosis (CAD) is rapidly entering the radiology mainstream. It has already become a part of the routine clinical work for the detection of breast cancer with mammograms. The computer output is used as a "second opinion" in assisting radiologists' image interpretations. The computer algorithm generally consists of several steps that may include image processing, image feature analysis, and data classification via the use of tools such as artificial neural networks (ANN). In this article, we will explore these and other current processes that have come to be referred to as "artificial intelligence." One element of CAD, temporal subtraction, has been applied for enhancing interval changes and for suppressing unchanged structures (eg, normal structures) between 2 successive radiologic images. To reduce misregistration artifacts on the temporal subtraction images, a nonlinear image warping technique for matching the previous image to the current one has been developed. Development of the temporal subtraction method originated with chest radiographs, with the method subsequently being applied to chest computed tomography (CT) and nuclear medicine bone scans. The usefulness of the temporal subtraction method for bone scans was demonstrated by an observer study in which reading times and diagnostic accuracy improved significantly. An additional prospective clinical study verified that the temporal subtraction image could be used as a "second opinion" by radiologists with negligible detrimental effects. ANN was first used in 1990 for computerized differential diagnosis of interstitial lung diseases in CAD. Since then, ANN has been widely used in CAD schemes for the detection and diagnosis of various diseases in different imaging modalities, including the differential diagnosis of lung nodules and interstitial lung diseases in chest radiography, CT, and position emission tomography/CT. It is likely that CAD will be integrated into picture archiving and communication systems and will become a standard of care for diagnostic examinations in daily clinical work. PMID- 21978448 TI - Redesigning the nuclear medicine reading room. AB - The process of image review and interpretation has become increasingly complex and challenging for today's nuclear medicine physician from many perspectives, especially with regard to workstation integration and reading room ergonomics. With the recent proliferation of hybrid imaging systems, this complexity has increased rapidly, along with the number of studies performed. At the same time, clinicians throughout the health care enterprise are expecting remote access to nuclear medicine images whereas nuclear medicine physicians require reliable access at the point of care to the electronic medical record and to medical images from radiology and cardiology. The authors discuss the background and challenges related to integration of nuclear medicine into the health care enterprise and provide a series of recommendations for advancing successful integration efforts. Also addressed are unique characteristics of the nuclear medicine environment as well as ergonomic, lighting, and environmental considerations in the design and redesign of the modern reading room. PMID- 21978449 TI - Expression of a Leishmaniadonovani nucleotide sugar transporter in Leishmaniamajor enhances survival in visceral organs. AB - Leishmania donovani and Leishmaniainfantum infections cause fatal visceral leishmaniasis, and Leishmaniamajor causes self healing cutaneous lesions. It is poorly understood what genetic differences between these Leishmania species are responsible for the different pathologies of infection. To investigate whether L.donovani species-specific genes are involved in visceral Leishmania infection, we have examined a L.donovani species-specific gene Ld1590 (ortholog of LinJ15_V3.0900) that is a pseudogene in L.major. We have previously shown that transgenic expression of L.donovani Ld1590 in L.major significantly increased the liver and spleen parasite burdens in infected BALB/c mice. In this study we report that Ld1590 potentially encodes a nucleotide sugar transporter (NST) which localizes in the L.donovani Golgi apparatus. Surprisingly, although transgenic expression of the Ld1590 NST increased L.major survival in visceral organs, deletion of Ld1590 NST in L.donovani had no significant effect on L.donovani survival in mice. These observations suggest that loss of the functional Ld1590 gene in L.major may have been associated with reduced virulence in visceral organs in its animal reservoir and could have contributed to L.major's tropism for cutaneous infections. PMID- 21978450 TI - The use of complete-case and multiple imputation-based analyses in molecular epidemiology studies that assess interaction effects. AB - BACKGROUND: In molecular epidemiology studies biospecimen data are collected, often with the purpose of evaluating the synergistic role between a biomarker and another feature on an outcome. Typically, biomarker data are collected on only a proportion of subjects eligible for study, leading to a missing data problem. Missing data methods, however, are not customarily incorporated into analyses. Instead, complete-case (CC) analyses are performed, which can result in biased and inefficient estimates. METHODS: Through simulations, we characterized the performance of CC methods when interaction effects are estimated. We also investigated whether standard multiple imputation (MI) could improve estimation over CC methods when the data are not missing at random (NMAR) and auxiliary information may or may not exist. RESULTS: CC analyses were shown to result in considerable bias and efficiency loss. While MI reduced bias and increased efficiency over CC methods under specific conditions, it too resulted in biased estimates depending on the strength of the auxiliary data available and the nature of the missingness. In particular, CC performed better than MI when extreme values of the covariate were more likely to be missing, while MI outperformed CC when missingness of the covariate related to both the covariate and outcome. MI always improved performance when strong auxiliary data were available. In a real study, MI estimates of interaction effects were attenuated relative to those from a CC approach. CONCLUSIONS: Our findings suggest the importance of incorporating missing data methods into the analysis. If the data are MAR, standard MI is a reasonable method. Auxiliary variables may make this assumption more reasonable even if the data are NMAR. Under NMAR we emphasize caution when using standard MI and recommend it over CC only when strong auxiliary data are available. MI, with the missing data mechanism specified, is an alternative when the data are NMAR. In all cases, it is recommended to take advantage of MI's ability to account for the uncertainty of these assumptions. PMID- 21978451 TI - Arabidopsis seedling flood-inoculation technique: a rapid and reliable assay for studying plant-bacterial interactions. AB - BACKGROUND: The Arabidopsis thaliana-Pseudomonas syringae model pathosystem is one of the most widely used systems to understand the mechanisms of microbial pathogenesis and plant innate immunity. Several inoculation methods have been used to study plant-pathogen interactions in this model system. However, none of the methods reported to date are similar to those occurring in nature and amicable to large-scale mutant screens. RESULTS: In this study, we developed a rapid and reliable seedling flood-inoculation method based on young Arabidopsis seedlings grown on MS medium. This method has several advantages over conventional soil-grown plant inoculation assays, including a shorter growth and incubation period, ease of inoculation and handling, uniform infection and disease development, requires less growth chamber space and is suitable for high throughput screens. In this study we demonstrated the efficacy of the Arabidopsis seedling assay to study 1) the virulence factors of P. syringae pv. tomato DC3000, including type III protein secretion system (TTSS) and phytotoxin coronatine (COR); 2) the effector-triggered immunity; and 3) Arabidopsis mutants affected in salicylic acid (SA)- and pathogen-associated molecular pattern (PAMPs)-mediated pathways. Furthermore, we applied this technique to study nonhost resistance (NHR) responses in Arabidopsis using nonhost pathogens, such as P. syringae pv. tabaci, pv. glycinea and pv. tomato T1, and confirmed the functional role of FLAGELLIN-SENSING 2 (FLS2) in NHR. CONCLUSIONS: The Arabidopsis seedling flood-inoculation assay provides a rapid, efficient and economical method for studying Arabidopsis-Pseudomonas interactions with minimal growth chamber space and time. This assay could also provide an excellent system for investigating the virulence mechanisms of P. syringae. Using this method, we demonstrated that FLS2 plays a critical role in conferring NHR against nonhost pathovars of P. syringae, but not to Xanthomonas campestris pv. vesicatoria. This method is potentially ideal for high-throughput screening of both Arabidopsis and pathogen mutants. PMID- 21978452 TI - ATOM - an OMERO add-on for automated import of image data. AB - BACKGROUND: Modern microscope platforms are able to generate multiple gigabytes of image data in a single experimental session. In a routine research laboratory workflow, these data are initially stored on the local acquisition computer from which files need to be transferred to the experimenter's (remote) image repository (e.g., DVDs, portable hard discs or server-based storage) because of limited local data storage. Although manual solutions for this migration, such as OMERO - a client-server software for visualising and managing large amounts of image data - exist, this import process may be a time-consuming and tedious task. FINDINGS: We have developed ATOM, a Java-based and thus platform-independent add on for OMERO enabling automated transfer of image data from a wide variety of acquisition software packages into OMERO. ATOM provides a graphical user interface and allows pre-organisation of experimental data for the transfer. CONCLUSIONS: ATOM is a convenient extension of the OMERO software system. An automated interface to OMERO will be a useful tool for scientists working with file formats supported by the Bio-Formats file format library, a platform independent library for reading the most common file formats of microscope images. PMID- 21978453 TI - Distribution and characteristics of ABFs, cecropins, nemapores, and lysozymes in nematodes. AB - Several groups of antimicrobial effector molecules have been identified in nematodes, but most studies have been limited to Caenorhabditis elegans and, to a lesser extent, Ascaris suum. Although these two species are not closely related, they are not representative of overall nematode diversity. This study utilized available sequence information to investigate whether four groups of antimicrobial effectors (defensin-like antibacterial factors [ABFs], cecropins, saposin domain-containing proteins, and lysozymes) are components of an archetypal nematode immune system or more narrowly restricted. Saposin domain containing proteins (caenopores in C. elegans) and lysozymes were widely distributed and found in most taxa, but likely have digestive as well as defensive functions. ABFs were widely distributed in fewer taxa, suggesting selective loss in some lineages. In contrast, cecropins were identified in only three related species, suggesting acquisition of this effector molecule in their common ancestor. PMID- 21978454 TI - Molecular characterizations and functional assessments of GATA-3 and its splice variant in Atlantic cod (Gadus morhua L.). AB - GATA-3 is a master transcription factor of the Th2 cells. We have identified GATA 3 cDNA and its splice variant in Atlantic cod. Cod GATA-3 (GmGATA-3) has a 1320 b p open reading frame encoding a polypeptide of 440 amino acids with two zinc finger domains that are well conserved within teleosts and higher vertebrates. The GATA-3 cDNA splice variant without zinc finger domains was shown to contain an 828 b p open reading frame encoding a polypeptide of 276 amino acids. Both GATA-3 proteins fused with RFP-tag were identified in or close to the nuclei 48 h after the plasmids were transfected in CHSE-214 cells. The full length GATA-3 with two zinc finger domains has a transcriptional function confirmed by transfection with GATA-3 reporter vector along with expression constructs of GATA 3 plasmids in CHSE-214 cells, whereas the GATA-3 splice variant without zinc finger domain did not enhance the activity of the GATA-3 reporter vector, and no interference was found between these two GATA-3 variants. RT-PCR analysis revealed that the two Atlantic cod GATA-3 variants were strongly expressed in the gills and infection with live Vibrio anguillarum induced the spleen expression of both GmGATA-3L and GmGATA-3S. Unexpectedly, PMA increased the expression of the GATA-3 splice variant in vivo and especially in vitro, with an increase of more than 100,000-fold in head kidney leukocytes at 24 and 48 h. On the other hand, there were no significant increases at the transcript level of full length GATA-3 between Poly I:C and beta-glucan treatment groups compared to controls. PMID- 21978455 TI - Embryotoxicity assays for leached components from dental restorative materials. AB - BACKGROUND: Currently, there are no suitable assays available to evaluate the embryotoxicity of leached components from restorative dental materials. METHODS: The effect of the medium conditioned by composites and amalgam on mouse blastocysts in vitro was tested. The materials were also subcutaneously implanted, and the effect of the medium supplemented with serum from the host blood was evaluated in the embryotoxicity assay. The embryo implantation rate in the material-transplanted mothers was also evaluated. RESULTS: The results show that while the culture in media conditioned by amalgams did not affect blastocyst development, the medium conditioned by composites caused blastocyst degeneration and apoptosis. The development of blastocysts in a medium containing serum obtained from animals after transplantation was, however, without effect. Finally, inconsistent reduction in the implantation rate in transplanted mothers was observed. CONCLUSIONS: In this study, we provide examples of in vitro and in vivo tests that may be used to evaluate embryotoxicity for dental materials. Our results show that leached components from our composite-material induced embryotoxicity in vitro, however, no toxicity was observed when subcutaneously implanted in vivo. This highlights the necessity of integrated in vitro and in vivo tests for valuable predictive estimation of embryotoxicity for complex materials. PMID- 21978456 TI - A clinically relevant gene signature in triple negative and basal-like breast cancer. AB - INTRODUCTION: Current prognostic gene expression profiles for breast cancer mainly reflect proliferation status and are most useful in ER-positive cancers. Triple negative breast cancers (TNBC) are clinically heterogeneous and prognostic markers and biology-based therapies are needed to better treat this disease. METHODS: We assembled Affymetrix gene expression data for 579 TNBC and performed unsupervised analysis to define metagenes that distinguish molecular subsets within TNBC. We used n = 394 cases for discovery and n = 185 cases for validation. Sixteen metagenes emerged that identified basal-like, apocrine and claudin-low molecular subtypes, or reflected various non-neoplastic cell populations, including immune cells, blood, adipocytes, stroma, angiogenesis and inflammation within the cancer. The expressions of these metagenes were correlated with survival and multivariate analysis was performed, including routine clinical and pathological variables. RESULTS: Seventy-three percent of TNBC displayed basal-like molecular subtype that correlated with high histological grade and younger age. Survival of basal-like TNBC was not different from non basal-like TNBC. High expression of immune cell metagenes was associated with good and high expression of inflammation and angiogenesis-related metagenes were associated with poor prognosis. A ratio of high B-cell and low IL-8 metagenes identified 32% of TNBC with good prognosis (hazard ratio (HR) 0.37, 95% CI 0.22 to 0.61; P < 0.001) and was the only significant predictor in multivariate analysis including routine clinicopathological variables. CONCLUSIONS: We describe a ratio of high B-cell presence and low IL-8 activity as a powerful new prognostic marker for TNBC. Inhibition of the IL-8 pathway also represents an attractive novel therapeutic target for this disease. PMID- 21978457 TI - HIV-1 transgene expression in rats induces differential expression of tumor necrosis factor alpha and zinc transporters in the liver and the lung. AB - BACKGROUND: Highly effective antiviral treatment can suppress HIV-1 infection, but the chronic effects of HIV-1-related viral proteins, including gp120 and Tat, on organs such as the lungs can be damaging. HIV-1 transgenic rodent models are useful for studying the systemic effects of these proteins independently of viral infection. We have previously shown that HIV-1 transgene expression (and therefore, HIV-1-related protein expression) in rats decreases alveolar macrophage zinc levels and phagocytic capacity by unknown mechanisms. We hypothesized that HIV-1 transgene expression induces chronic inflammation and zinc sequestration within the liver and thereby decreases zinc bioavailability in the lung. We examined the expression of the pro-inflammatory cytokine, tumor necrosis factor alpha (TNFalpha), the zinc storage protein, metallothionein (MT1), and the zinc exporter, ZNT1 in the livers and the lungs of wild type and HIV-1 transgenic rats +/- dietary zinc supplementation. In addition, we measured zinc levels, the zinc importing protein ZIP1, and the phagocytic capacity in the alveolar macrophages. RESULTS: HIV-1 transgene expression increased the liver specific expression of TNFalpha, suggesting a chronic inflammatory response within the liver in response to HIV-1-related protein expression. In parallel, HIV-1 transgene expression significantly increased MT1 and ZNT1 expression in the liver as compared to the lung, a pattern that is consistent with zinc sequestration in the liver as occurs during systemic inflammation. Further, HIV-1 transgene expression decreased intracellular zinc levels and increased expression of ZIP1 in the alveolar macrophages, a pattern consistent with zinc deficiency, and decreased their bacterial phagocytic capacity. Interestingly, dietary zinc supplementation in HIV-1 transgenic rats decreased gene expression of TNFalpha, MT1, and ZNT1 in the liver while simultaneously increasing their expression in the lung. In parallel, zinc supplementation increased alveolar macrophage intracellular zinc levels and bacterial phagocytic capacity in HIV-1 transgenic rats. CONCLUSION: Taken together, these findings suggest that chronic HIV-1 related protein expression causes liver inflammation and zinc sequestration, which in turn limits zinc bioavailability in the lung and thereby impairs alveolar macrophage phagocytic function. Importantly, dietary zinc supplementation decreases liver inflammation and zinc sequestration and restores alveolar macrophage phagocytic function in HIV-1 transgenic rats, a result with potential clinical implications for improving lung health in HIV-1-infected individuals. PMID- 21978458 TI - Elevated Kruppel-like factor 4 transcription factor in canine mammary carcinoma. AB - BACKGROUND: Kruppel-like factors (KLFs) are critical regulators of biological and physiological systems and have been extensively studied for their roles in cell proliferation, differentiation and survival in the context of cancer. Among the KLFs, KLF4 is highly expressed in human breast cancers and plays an oncogenic role. The present study examined the expression of KLF4 and assessed its significance in canine mammary carcinoma. RESULTS: Immunohistochemistry was employed to investigate the expression of KLF4 in 142 cases of canine mammary tumor. 75 of the 142 (52.8%) cases were histologically confirmed as mammary carcinoma. Quantification of immunohistochemistry was carried out using Quick score which multiply the staining intensity by the percentage of positive cells. High KLF4 expression was identified in 44 of the 75 (59%) dogs with mammary carcinoma and none in the benign cases. High KLF4 expression occurred only in the tumor cells and not the adjacent normal cells in mammary carcinoma (P < 0.001). Moreover, the high expression level of KLF4 expression was statistically associated with poor grade, late stage, histological subtypes of simple and complex carcinoma, and shorter 24-month survival. The Kaplan-Meier survival analysis also indicated that dogs with high nuclear KLF4 expression had a significantly shorter survival than those with low/moderate KLF4 expression (P = 0.011). CONCLUSIONS: KLF4 is highly and frequently expressed in canine mammary carcinoma and correlates with a more aggressive phenotype. PMID- 21978459 TI - Diverticular disease of the right colon. AB - BACKGROUND: The incidence of colonic diverticular disease varies with national origin, cultural background and diet. The frequency of this disease increases with advancing age. Right-sided diverticular disease is uncommon and reported to occur in 1-2% of surgical specimens in European and American series. In contrast the disease is more prevalent and reported in 43-50% of specimens in Asian series. Various lines of evidence suggest this variation may represent hereditary differences. The aim of the study is to report all cases of right sided diverticular disease underwent surgical resection or identified during pathological examination of right hemicoloectomy specimens METHODS: A retrospective review of all surgical specimens with right sided colonic diverticular disease selected from a larger database of all colonic diverticulosis and diverticulitis surgical specimen reported between January 1993 and December 2010 at the Pathology Department McMaster University Medical Centre Canada. The clinical and pathological features of these cases were reviewed RESULTS: The review identified 15 cases of right colon diverticulosis. The clinical diagnoses of these cases were appendicitis, diverticulitis or adenocarcinoma. Eight cases of single congenital perforated diverticuli were identified and seven cases were incidental multiple acquired diverticuli found in specimen resected for right side colonic carcinomas/large adenomas. Laparotomy or laparoscopic assisted haemicolectomies were done for all cases. Pathological examination showed caecal wall thickening with inflammation associated with perforated diverticuli. Histology confirmed true solitary diverticuli that exhibited in two cases thick walled vessels in the submucosa and muscular layer indicating vascular malformation/angiodysplasia. Acquired diverticuli tend to be multiple and are mostly seen in specimens resected for neoplastic right colon diseases. CONCLUSION: Single true diverticular disease of the right colon is usually of congenital type and affects younger age group and may be associated with angiodysplasia in some cases. Multiple false diverticuli are more seen in association with caecal carcinoma or large adenomas. These are usually asymptomatic and are more seen in older patients. However this study dose not reflects the true incidence of the disease in the general population. PMID- 21978461 TI - Brain injury clinical trials: new agents or new statistics? AB - Failure of the vast majority of clinical trials evaluating recovery after severe brain injury from stroke or trauma has triggered interest in novel statistical techniques that are more powerful than conventional dichotomized outcomes. A retrospective analysis of data from a large international trial evaluating high dose steroids for severe traumatic brain injury found that analysis of a wide range of outcome levels by using an ordinal scale with proportional odds regression or a sliding dichotomy was more likely to detect a treatment effect than the single-dichotomy approach. These techniques may soon become commonplace as critical care research increasingly focuses on patient-centered functional outcomes. PMID- 21978460 TI - Differential expression of alpha 2 macroglobulin in response to dietylstilbestrol and in ovarian carcinomas in chickens. AB - BACKGROUND: Alpha 2 macroglobulin (A2M; also known as ovostatin), a homotetrameric protein with four disulfide-linked subunits, has the unique feature of inactivating/inhibiting most known proteases including serine-, threonine-, cysteine-, aspartic- and metalloproteases. In chickens, A2M has been identified and characterized biochemically, but little is known of its functional role(s) in the oviduct, hormonal regulation of expression or its expression in ovarian carcinomas in chickens. Therefore, we investigated estrogen regulation of A2M gene expression during development of the chicken oviduct, and its expression in normal and cancerous ovaries from chickens. METHODS: To determine tissue specific expression of A2M in chickens, we collected various organs from male and female chickens and performed RT-PCR analyses. To examine A2M gene expression in the oviduct of 1-week-old female chicks that received a subcutaneous implant of 15 mg DES in the abdominal region for 20 days, we performed RT-PCR, qPCR and in situ hybridization analyses using cDNAs from control- (n=5) and DES-treated oviducts (n=5), and then each segment of the oviduct from DES-treated chicks. To determine if A2M is a biomarker of ovarian cancer in hens, we collected cancerous (n=10) ovaries from a total of 136 chickens which had completely stopped egg laying and performed RT-PCR and in situ hybridization analyses. RESULTS: We found that A2M is most abundant in the chicken oviduct, specifically luminal (LE) and glandular epithelia (GE), but it was not detected in any other tissues of either sex. We then determined that DES (dietylstilbestrol, a synthetic nonsteroidal estrogen) increased A2M mRNA only in LE and GE of the oviduct of chicks. Further, expression of A2M was most abundant in GE of endometrioid adenocarcinoma of cancerous, but not normal ovaries of hens. CONCLUSIONS: Collectively, results of the present study indicate that A2M is novel estrogen-stimulated gene expressed in LE and GE of the chicken oviduct and may be used for monitoring effects of therapies for ovarian cancer in laying hens. PMID- 21978462 TI - A validation study using a modified version of Postural Assessment Scale for Stroke Patients: Postural Stroke Study in Gothenburg (POSTGOT). AB - BACKGROUND: A modified version of Postural Assessment Scale for Stroke Patients (PASS) was created with some changes in the description of the items and clarifications in the manual (e.g. much help was defined as support from 2 persons). The aim of this validation study was to assess intrarater and interrater reliability using this modified version of PASS, at a stroke unit, for patients in the acute phase after their first event of stroke. METHODS: In the intrarater reliability study 114 patients and in the interrater reliability study 15 patients were examined twice with the test within one to 24 hours in the first week after stroke. Spearman's rank correlation, Kappa coefficients, Percentage Agreement and the newer rank-invariant methods; Relative Position, Relative Concentration and Relative rank Variance were used for the statistical analysis. RESULTS: For the intrarater reliability Spearman's rank correlations were 0.88 0.98 and k were 0.70-0.93 for the individual items. Small, statistically significant, differences were found for two items regarding Relative Position and for one item regarding Relative Concentration. There was no Relative rank Variance for any single item.For the interrater reliability, Spearman's rank correlations were 0.77-0.99 for individual items. For some items there was a possible, even if not proved, reliability problem regarding Relative Position and Relative Concentration. There was no Relative rank Variance for the single items, except for a small Relative rank Variance for one item. CONCLUSIONS: The high intrarater and interrater reliability shown for the modified Postural Assessment Scale for Stroke Patients, the Swedish version of Postural Assessment Scale for Stroke Patients, with traditional and newer statistical analyses, particularly for assessments performed by the same rater, support the use of the Swedish version of Postural Assessment Scale for Stroke Patients, in the acute stage after stroke both in clinical and research settings. In addition, the Swedish version of Postural Assessment Scale for Stroke Patients was easy to apply and fast to administer in clinic. PMID- 21978463 TI - The prognostic value of the nodal ratio in N1 breast cancer. AB - BACKGROUND: Although the nodal ratio (NR) has been recognized as a prognostic factor in breast cancer, its clinical implication in patients with 1-3 positive nodes (N1) remains unclear. Here, we evaluated the prognostic value of the NR and identified other clinico-pathologic variables associated with poor prognosis in these patients. METHODS: We analyzed 130 patients with N1 invasive breast cancer who were treated at Seoul National University Bundang Hospital from March 2003 to December 2007. Disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were compared according to the NR with a cut-off value of 0.15. RESULTS: We followed patients' recovery for a median duration of 59 months. An NR > 0.15 was found in 23.1% of patients, and a median of 18 nodes were dissected per patient (range 1-59). The NR was statistically independent from other prognostic variables, such as patient age, T stage, extent of surgery, pathologic factors in the chi square test. On univariate analysis, patients with a NR > 0.15 had significantly lower 5-year LRRFS (88.7% vs. 97.9%, p = 0.033) and 5-year DMFS (81.3% vs. 96.4%, p = 0.029) and marginally lower 5-year DFS (81.3% vs. 94.0%, p = 0.069) than those with a NR <=0.15, respectively. Since the predictive power of the NR was found to differ with diverse clinical and pathologic variables, we performed adjusted analysis stratified by age, pathologic characteristics, and adjuvant treatments. Only young patients with a NR > 0.15 showed significantly lower DFS (p = 0.027) as well as those presenting an unfavorable pathologic profile such as advanced T stage (p = 0.034), histologic grade 3 (p = 0.034), positive lymphovascular invasion (p = 0.037), involved resection margin (p = 0.007), and no chemotherapy (p = 0.014) or regional radiotherapy treatment (p = 0.039). On multivariate analysis, a NR > 0.15 was significantly associated with lower DFS (p = 0.043) and DMFS (p = 0.012), but not LRRFS (p = 0.064). CONCLUSIONS: A NR > 0.15 was associated with an increased risk of recurrence, especially in young patients with unfavorable pathologic profiles. PMID- 21978464 TI - What do we need to know about speciation? AB - Speciation has been a major focus of evolutionary biology research in recent years, with many important advances. However, some of the traditional organising principles of the subject area no longer provide a satisfactory framework, such as the classification of speciation mechanisms by geographical context into allopatric, parapatric and sympatry classes. Therefore, we have asked where speciation research should be directed in the coming years. Here, we present a distillation of questions about the mechanisms of speciation, the genetic basis of speciation and the relationship between speciation and diversity. Our list of topics is not exhaustive; rather we aim to promote discussion on research priorities and on the common themes that underlie disparate speciation processes. PMID- 21978465 TI - From snout to beak: the loss of teeth in birds. AB - All living birds are toothless, constituting by far the most diverse toothless vertebrate clade, and are striking examples of evolutionary success following tooth loss. In recent years, an unprecedented number of Mesozoic birds have been described, illustrating the evolution of dentition reductions. Simultaneously, major advances in experimental embryology have yielded new results concerning avian edentulism. Reviewing these lines of evidence, we propose hypotheses for its causes, with a prominent role for the horny beak during development. A horny beak and a muscular gizzard functionally 'replaced' dentition for food acquisition and processing, respectively. Together with edentulism itself, these features and others contributed to the later success of birds, as a result of their high performance or additional functionality working in concert in these complex organisms. PMID- 21978466 TI - The war against error: a 15 year experience of completion angioscopy following carotid endarterectomy. AB - BACKGROUND: A policy of intra-operative transcranial Doppler (TCD) and completion angioscopy was previously associated with virtual abolition of intra-operative stroke (apparent upon recovery from anaesthesia) following carotid endarterectomy (CEA). The aims of this study were to determine whether the prevalence of technical error has diminished with experience and whether our monitoring/quality control policy was still associated with low rates of intra-operative stroke 20 years after its introduction. METHODS: Retrospective review of four consecutive cohorts of 400 patients undergoing CEA between October 1995 and March 2010 (1600 CEAS in total). RESULTS: One hundred four patients (7%) had thrombus removed following angioscopy and prior to flow restoration, while 31 (2.1%) underwent repair of a distal intimal flap. The prevalence of intimal flaps diminished from 4.9% in the first 400 patients to 0.8% in the last 400 patients (p = 0.006). By contrast, the prevalence of retained thrombus did not decline with experience (8.5%, 3.7%, 10.3% and 5.4% for the four consecutive periods). Intra-operative TCD and completion angioscopy was, however, associated with extremely low rates of intra-operative stroke (0.25%, 0.25%, 0.5% and 0.25% during the four study periods). CONCLUSION: Most intra-operative strokes probably follow embolisation of thrombus following restoration of flow. This can be prevented by angioscopy which has the advantage of being performed prior to flow restoration. Increasing experience was associated with a decline in the detection of intimal flaps, but not in the prevalence of retained thrombus. Even the most experienced of surgeons can still be responsible for inadvertent technical error. PMID- 21978467 TI - Bortezomib resistance in a myeloma cell line is associated to PSMbeta5 overexpression and polyploidy. AB - Bortezomib is a proteasome inhibitor important to the therapy of multiple myeloma (MM), though a number of patients show resistance to this drug. To study the cellular basis of this resistance we have generated a MM cell line displaying enhanced (5-6-fold) resistance to bortezomib by serial cultivation of RPMI 8226 cells with increasing concentrations of this drug. Bortezomib-resistant cells (8226/7B) became bigger in size than parental cells and nearly doubled the amount of DNA per cell, evolving from hypotriploidy to near-tetraploidy. 8226/7B displayed lowered Noxa accumulation and reduced caspase-3 activation in response to bortezomib. Resistant 8226/7B cells overexpressed the PSMbeta5 proteasome subunit, the molecular target of bortezomib, both at the mRNA and protein level. No mutations were detected in the PSMbeta5 gene. Bortezomib-resistant cells were roughly as sensitive as parental cells to other chemotherapeutic drugs, including doxorubicin, melphalan, vincristine, BMS-214662 and BMS-345541. 8226/7B cells showed partial and high cross-resistance to the proteasome inhibitors epoxomicin and MG-132, respectively. Co-treatment with the histone deacetylase inhibitor trichostatin A (TSA) potentiated bortezomib-induced apoptosis in parental RPMI 8226 cells but did not revert bortezomib resistance in 8226/7B cells. Therefore, treatment of bortezomib-refractory myeloma with drugs targeting molecular structures other than proteasome seems to be the more suitable therapeutic strategy to overcome bortezomib resistance. PMID- 21978468 TI - Role of neuropilin-1 and its expression in Egyptian acute myeloid and acute lymphoid leukemia patients. AB - Neuropilins are expressed in tumors vasculature and cells. Their expression is thought to be correlated with tumor angiogenesis and progression. In this study, we analyzed NRP-1 expression level in 40 acute leukemia patients [20 acute myeloid leukemia (AML) and 20 acute lymphoblastic leukemia (ALL)] and 10 healthy controls using Real-Time Quantitative Reverse-Transcriptase Polymerase Chain Reaction (RTQ-PCR) aiming to show Neuropilin-1 (NRP-1) gene expression pattern in acute leukemia patients and its role in disease severity and progression. NRP-1 was expressed in 80% and 95% of ALL and AML respectively with levels higher in patients than controls and in ALL than AML patients. NRP-1 levels were significantly correlated with blast percentage and complete remission. We conclude that NRP-1 is significantly associated with acute leukemia and that its level might serve as an indicator for disease severity and progression. NRP-1 signaling may represent a novel therapeutic approach for the treatment of acute leukemia subsets. PMID- 21978469 TI - Clomiphene treatment of acute myeloid leukemia. PMID- 21978470 TI - Effect of corpus callosotomy on attention deficit and behavioral problems in pediatric patients with intractable epilepsy. AB - To evaluate the effect of corpus callosotomy (CC) on attention deficit and behavioral problems in pediatric patients with intractable epilepsy, we retrospectively investigated sequential patients who had undergone CC to control seizures. Between August 2005 and April 2010, a total of 15 patients aged between 3.1 and 17.9 years underwent CC at our institute. All the patients experienced either drop attacks or head nodding, which were considered to be therapeutic targets of CC. A standardized instrument, the Child Behavior Checklist (CBCL), was used to assess behavioral and emotional problems before and after surgery. On postoperative EEGs, 8 (53%) showed improvement and 7 (47%) showed no change in epileptiform discharges. The Attention Problems scale and total score on the CBCL significantly improved in patients whose postoperative EEGs showed improvement. In addition to amelioration of target seizures, CC can improve attention impairments in association with improvement in the postoperative EEG. PMID- 21978471 TI - Registry initiated to characterize vision loss associated with vigabatrin therapy. AB - The vigabatrin patient registry was implemented in August 2009 in conjunction with Food and Drug Administration approval of vigabatrin. All US vigabatrin treated patients must enroll in the registry. Data on prescriber specialty/location, patient demographics, and clinical characteristics are collected. Benefit-risk assessments are required early in the course of therapy. Vision assessments are required at baseline (<=4 weeks after therapy initiation), every 3 months during therapy, and 3 to 6 months after discontinuation. As of February 1, 2011, 2473 patients (1500 with infantile spasms, 846 with refractory complex partial seizures, 120 with other diagnoses) had enrolled; 30.4% were previously exposed to vigabatrin. Kaplan-Meier analysis of time in registry indicated that 83 and 97% of all enrolled patients with refractory complex partial seizures and infantile spasms remained beyond 3 and 1 month, respectively. The ongoing registry will provide visual status and other information on vigabatrin-treated patients for both the infantile spasm and refractory complex partial seizure indications. PMID- 21978472 TI - Use of an internal bidirectional distractor to elongate goats' mandibles. AB - We investigated the feasibility of using an internal bidirectional mandibular distractor to elongate the mandibular bodies and rami of 4 mature male goats. An osteotomy was made at the right mandibular angle and the distractor placed within the osteotomy and allowed to heal in place for 5 days. The mandibles were simultaneously distracted vertically and horizontally at a rate of 0.5mm/day for 30 days. After a 12-week consolidation period, all the goats were killed for gross, radiographic, and histological evaluation. Smooth new bone had been restored in the distracted area after 12 weeks' consolidation, and the gross, radiographic, and histological evaluations showed that the new bone was similar to the native bone. These results suggest that the internal bidirectional distractor could permit bidirectional distraction osteogenesis in a goat model. PMID- 21978473 TI - Radiation dose and diagnostic accuracy of multidetector computed tomography for the detection of significant coronary artery stenoses: a meta-analysis. AB - We conducted a meta-analysis evaluating the critical ratio between effective radiation dose (ED), feasibility (Fe) and diagnostic accuracy (Ac) of multidetector computed tomography (MDCT) for the detection of significant coronary artery disease. By using our predetermined criteria, we selected human studies published in English in which the ED and raw data of Ac vs. invasive coronary angiography in a segment based model were specified. Data from 31 studies including 3661 patients (mean age 61.9 +/- 4.5 years, heart rate 62.5 +/- 6.7 bpm) and 50,236 coronary artery segments were analysed and are reported. Overall, Fe, sensitivity, specificity, negative predictive value, positive predictive value, Ac and ED were 95%, 90%, 96%, 99%, 69%, 95% and 10.4 +/- 5.4 mSv, respectively. Multivariate analysis showed that prospective ECG-gating (-8.8 mSv CI95% -13.4 to -4.3 mSv, p=0.001), dual-source (-3.7 mSv CI95% -7.9 to 0 mSv, p=0.05) and BMI-adapted scanning protocols (-4.5 mSv CI95% -8.7 to -2.7 mSv, p=0.03) were independent predictors of ED reduction. In patients with low heart rate, the best compromise between ED, Fe and Ac (2.5 mSv, 97% and 98%, respectively) was obtained combining prospective ECG-gating and BMI-adapted scanning protocols, while in patients with high heart rate the strategy associated with the best results (10 mSv, 98% and 97%, respectively) was the use of dual-source MDCT with retrospective ECG gating and modulation dose. In conclusion, careful selection of CT scanning protocols according to the patient's characteristics is critical for keeping the radiation exposure "as low as reasonably achievable" (ALARA) without impairing Fe and Ac. PMID- 21978474 TI - Tombstone-like electrocardiographic changes during exercise stress test. AB - A 45-year-old man showed tombstone-like electrocardiographic change during stage 1 of stress testing, using Bruce protocol. The raw rhythm strip did not show any ST-T changes. These pseudochanges were probably the result of computer synthesized averaging algorithm errors. PMID- 21978475 TI - A V-shaped ligand 1,3-bis(1-methylbenzimidazol-2-yl)-2-oxapropane and its Cu(II) complex: synthesis, crystal structure, antioxidation and DNA-binding properties. AB - A six-coordinate copper(II) complex with the ligand 1,3-bis(1-methylbenzimidazol 2-yl)-2-oxopropane (Meobb), with composition [Cu(Meobb)(2)](NO(3))(2).2CH(3)OH, has been synthesized and characterized by elemental analysis, electrical conductivities, IR, UV-Vis spectral measurements. A study of the electro chemistry of the copper(II) complex was carried out by using cyclic voltammetry. The molecular structures of the ligand Meobb and the Cu(II) complex were determined by X-ray crystal diffraction. The DNA-binding modes of the ligand and the complex were investigated by electronic absorption titration, ethidium bromide-DNA displacement experiments and viscosity measurements. The experimental evidence indicated the compounds interact with calf thymus DNA through intercalation. Additionally, the Cu(II) complex exhibited potential antioxidant properties in in vitro studies. PMID- 21978476 TI - Pulmonary aspergillosis in non-immunocompromised patient with acute respiratory distress syndrome during A (H1N1) infection. PMID- 21978477 TI - [Bradykinin-mediated angioedema secondary to angiotensin converting enzyme: initiate treatment from the prehospital phase]. AB - We are reporting the case of a bradykinin-mediated angioedema, secondary to the angiotensin converting enzyme inhibitors, which delayed treatment could have unfavorably influence the vital prognostic of the patient. Initially, the patient had an isolated edema of the superior lip. Prehospital treatment included methylprednisolone, hydroxyzine and epinephrine. The patient was subsequently taken to the emergency department. His situation deteriorated. An edema of the cheeks and the tongue appeared. The transfer of the patient to an emergency department, specializing in kinin angioedema was organized, in order for the patient to receive specific treatments. After a subcutaneous injection of icatibant, the situation improved very rapidly, with a regression of the edema. This observation is consistent with the early use of the specific therapeutic in bradykinin-mediated angioedema. Any delay in administering the treatment can negatively impact the prognostic. The availability of such treatments should therefore be organized during the prehospital phase. PMID- 21978478 TI - French survey on current use of ultrasound in the critical care unit: ECHOREA. AB - INTRODUCTION: Over the last ten years, ultrasound became standard procedure in the intensive care unit (ICU). STUDY DESIGN: A national survey to evaluate the use of this technique in French ICUs. METHODS: Three hundred and twenty-seven units were contacted from the listing of the Societe de reanimation de langue francaise (SRLF). A survey containing 20 questions addressing the availability, the training for, and the use of ultrasound was sent to the ICUs. Collection of data took place over a period of three months. RESULTS: We received 132 completed surveys out of the 327 sent out (40%). Seventy-nine percent of the public community and private centers and 94% of the university centers had an available device in the unit. Forty percent of the units carried out five to ten examinations per week. Seventy-two percent had staff trained in echocardiography. Fifty-five percent used association of monitoring techniques for the haemodynamic assessment of patients with shock. Only 73% carried out formalized reports after examination. In more than 80%, the echocardiograph was also used for the evaluation of other organs. CONCLUSION: Ultrasound, and particularly echocardiography, has taken on a more prominent role in the routine assessment of critically ill patients. The availability of equipment and of training has increased over the last ten years, but the demand for training in this area remains strong. This French survey confirms this technique became the "extension of the hand" of the intensivist in ICU. PMID- 21978479 TI - [Acute legionnaires myocarditis: a difficult diagnosis]. PMID- 21978480 TI - [Haemophagocytic lymphohistiocytosis syndrome: a possible cause of multi-organ failure in severe head trauma?]. AB - We report the case of a 26-year-old patient who was victim of severe head trauma following a trafic road accident. Two days after trauma, she had fever, pancytopenia and multi-organ failure. The haemophagocytic lymphohistiocytosis syndrome was suspected. This diagnosis was confirmed by biologic findings (elevated serum levels of ferritin and triglycerid) and histological findings (examination of bone marrow smears showing histiocytes phagocytosing blood cells). The evolution was unfavorable despite of corticotherapy and symptomatic measures. PMID- 21978481 TI - Nodular hemangiomatosis of pleura and peritoneum. AB - Multiple, simultaneously occurring hemangiomas in one or more organs are known as hemangiomatosis syndromes in the context of phacomatosis manifesting in childhood. Nevertheless, hemangiomas of the serous membranes are extremely rare and often present as solitary lesions. We report the case of an elderly patient who suffered from diffuse hemangiomatosis of the visceral peritoneum and pleura and deceased due to acute respiratory distress syndrome following persistent and unmanageable pulmonary hemorrhage. We present an unusual case of a disseminated but histologically benign appearing hemangiomatosis of the serous membranes. PMID- 21978482 TI - Health Policy and Systems Research in Twelve Eastern Mediterranean Countries: a stocktaking of production and gaps (2000-2008). AB - BACKGROUND: The objectives of this study are to: (1) profile the production of Health Policy and Systems Research (HPSR) published between 2000 and 2008 in 12 countries in the Eastern Mediterranean Region (EMR): Bahrain, Egypt, Jordan, Lebanon, Libya, Morocco, Oman, Palestine, Sudan, Syria, Tunisia, and Yemen; (2) identify gaps; and (3) assess the extent to which existing HPSR produced in the region addresses regional priorities pertaining to Health Financing, Human Resources for Health and the Role of the Non-State Sector. This is the first stocktaking paper of HPSR production and gaps in the EMR. METHODS: Articles indexed on Medline between years 2000 and 2008 for the 12 study countries were selected. A MeSH term based search was conducted using country names. Articles were assessed using a coding sheet adapted for the region which included themes on: Governance Arrangements, Financial Arrangements, Delivery Arrangements, and Implementation Strategies. Identified articles were matched against regional research priorities to assess the extent to which research production aligns with priorities. RESULTS: A total of 1,487 articles (11.94%) fit the criteria in the coding sheet. Results showed an increase in HPSR production which peaked after 2005. Most identified articles focused on Delivery Arrangements (68.1%), and Implementation Strategies (24.4%). Most HPSR addressed priorities in Human Resources for Health (39%), and some articles focused on Health Financing (12%) and Role of the Non-State Sector (6.1%). CONCLUSIONS: Despite global calls for producing and translating HPSR into policy, there are still significant gaps in the EMR. More efforts are needed to produce HPSR and align production and translation with the demand for evidence by policymakers. Findings can help inform and direct future plans and activities for the Evidence Informed Policy Network- EMR, World Health Organization- EMR, and the Middle East and North Africa Health Policy Forum, in addition to being useful for countries that host or are planning to host KT platforms in the region. PMID- 21978483 TI - Specific detection of cysteine and homocysteine in biological fluids by tuning the pH values of fluorosurfactant-stabilized gold colloidal solution. AB - This study describes the use of 14 nm nonionic fluorosurfactant-capped gold nanoparticles (FSN-capped AuNPs) for the simultaneous detection of cysteine (Cys) and homocysteine (Hcy) using colorimetric method, requiring no use of separation techniques. It was found that the kinetics of Cys/Hcy-induced aggregation of the 14 nm FSN-capped AuNPs strongly depends on the pH value of gold colloidal solution. At a pH of 6.5, the Cys-induced aggregation kinetics of the FSN-capped AuNPs was almost identical to that induced by Hcy, facilitating simultaneous detection of total Cys and Hcy up to a concentration as low as 0.15 MUM; while at pH 12.0, the kinetics of Cys-induced aggregation was much faster than that inducted by Hcy, leading to selective detection of Cys at concentration as low as 1.0 MUM in the presence of Hcy. The applicability of the method was validated by spiking known amount of Cys and Hcy in human urine and plasma samples, obtaining a recovery of 95.4-105.5%. The present approach is simple, high selective and provides high reproducibility, and has a great potentiality in disease diagnosis. PMID- 21978484 TI - Reduction of autofluorescence at the microelectrode-cortical tissue interface improves antibody detection. AB - Immunohistochemistry (IHC) remains among the most utilized methods for detection of inflammatory events occurring at the microelectrode-cortical tissue interface. It has further become a standard protocol to quantify the intensity of this resulting fluorescent signal, normalized to "background", as a measurement of the extent of inflammatory events. Unfortunately, several sources of autofluorescence could result in variations in this user-defined "background". Notably, we found that the presence of hemosiderin-laden macrophages (HLMs) at the interface resulted in a variable source of background in both green and red fluorescent channels. The HLM-derived autofluorescence prevented the reproducible detection of presumably low-level antigens at the interface. Here we show that treatment of the native cortical tissue for no less than 10 min, with a minimum of 0.5mM copper sulfate, resulted in at least a 70% reduction in native HLM autofluorescence in both green and red fluorescent channels. In the case of highly expressed antigens, such as glial fibrillar acidic protein (GFAP), treatment of immuno-labeled tissue with copper sulfate reduced tissue background, compared to standard IHC methodology, but did not result in significant differences in the quantification of normalized signal intensity. However, treatment with copper sulfate substantially enhanced the detection efficiency of weakly expressed antigens at the device-tissue interface. This study demonstrates that the inclusion of copper sulfate incubation during IHC tissue preparation significantly reduced HLM-derived autofluorescence, and allowed for more accurate detection and quantification of faintly expressed inflammatory markers at the device-tissue interface. PMID- 21978485 TI - Knockdown of cortical transthyretin expression around implanted neural prosthetic devices using intraventricular siRNA injection in the brain. AB - Neural prosthetic devices are showing increasing clinical use for the treatment of a variety of neurological disorders. However the functions on these devices are often limited due to an inability to effectively and chronically interface with neural tissue. The insertion of devices has been shown to result in significant cellular and vascular trauma surrounding the insertion site. In particular, the up-regulation of genes involved in neuronal degeneration are believed to contribute to the loss of neuronal tissue. RNA interference is a novel technique for the development of antisense therapeutics for the post transcriptional silencing of specific genes. In order to demonstrate the feasibility of RNA interference for gene-specific silencing in vivo, a short interfering RNA targeting transthyretin, was infused prior to unilateral device insertion. Injection of siRNA was found to significantly reduce the expression of transthyretin mRNA when expression was assessed at 1 week following device insertion. Concomitant decreases in transthyretin protein levels were also observed. These data demonstrate the feasibility of using RNA interference to modulate the initial reactive cellular responses that occur in the brain following insertion of neural prosthetic devices. PMID- 21978486 TI - Optimization of seed density in DTI tractography for structural networks. AB - Diffusion tensor imaging (DTI) has been used for mapping the structural network of the human brain. The network can be constructed by choosing various brain regions as nodes and fiber tracts connecting those regions as links. The structural network generated from DTI data can be affected by noise in the scans and the choice of tractography algorithm. This study aimed to examine the effect of the number of seeds in tractography on the variance of structural networks. The variance of the network was characterized using an approach similar to the National Electrical Manufacturers Association (NEMA) standards for measurement of image noise. It was shown that the variance of the network is inversely related to the square root of seed density. Consequently, the number of seeds has a large impact on local characteristics and metrics of the network architecture. As the number of seeds increased, increased stability of structural network metrics was observed. However, more seeds can also lead to more spurious fibers and thus affect nodal degrees and edge weights, and proper thresholding may be necessary to create an appropriate weighted network. Because the variance of the network is also influenced by other imaging factors, further increase in the number of seeds has little effect in reducing the network variance. The selection of the seed number should be a balance between the network variance and computational effort. PMID- 21978487 TI - Feasibility of home-based automated Parkinson's disease motor assessment. AB - Patients with Parkinson's disease (PD) receive therapies aimed at addressing a diverse range of motor symptoms. Motor complications in the form of symptom fluctuations and dyskinesias that commonly occur with chronic PD medication use may not be effectively captured by Unified Parkinson's Disease Rating Scale (UPDRS) assessments performed in the clinic. Therefore, home monitoring may be a viable adjunct tool to provide insight into PD motor symptom response to treatment. In this pilot study, we sought to evaluate the feasibility of capturing PD motor symptoms at home using a computer-based assessment system. Ten subjects diagnosed with idiopathic PD used the system at home and ten non-PD control subjects used the system in a laboratory. The Kinesia system consists of a wireless finger-worn motion sensor and a laptop computer with software for automated tremor and bradykinesia severity score assessments. Data from control subjects were used to develop compliance algorithms for rejecting motor tasks performed incorrectly. These algorithms were then applied to data collected from the PD subjects who used the Kinesia system at home to complete motor exams 3-6 times per day over 3-6 days. Motor tasks not rejected by the compliance algorithms were further processed for symptom severity. PD subjects successfully completed motor assessments at home, with approximately 97% of all motor task data files (1222/1260) accepted. These findings suggest that objective home monitoring of PD motor fluctuations is feasible. PMID- 21978488 TI - Hydrogen, metals, bifurcating electrons, and proton gradients: the early evolution of biological energy conservation. AB - Life is a persistent, self-specified set of far from equilibrium chemical reactions. In modern microbes, core carbon and energy metabolism are what keep cells alive. In very early chemical evolution, the forerunners of carbon and energy metabolism were the processes of generating reduced carbon compounds from CO(2) and the mechanisms of harnessing energy as compounds capable of doing some chemical work. The process of serpentinization at alkaline hydrothermal vents holds promise as a model for the origin of early reducing power, because Fe(2+) in the Earth's crust reduces water to H(2) and inorganic carbon to methane. The overall geochemical process of serpentinization is similar to the biochemical process of methanogenesis, and methanogenesis is similar to acetogenesis in that both physiologies allow energy conservation from the reduction of CO(2) with electrons from H(2). Electron bifurcation is a newly recognized cytosolic process that anaerobes use generate low potential electrons, it plays an important role in some forms of methanogenesis and, via speculation, possibly in acetogenesis. Electron bifurcation likely figures into the early evolution of biological energy conservation. PMID- 21978489 TI - Medusa: A tool for exploring and clustering biological networks. AB - BACKGROUND: Biological processes such as metabolic pathways, gene regulation or protein-protein interactions are often represented as graphs in systems biology. The understanding of such networks, their analysis, and their visualization are today important challenges in life sciences. While a great variety of visualization tools that try to address most of these challenges already exists, only few of them succeed to bridge the gap between visualization and network analysis. FINDINGS: Medusa is a powerful tool for visualization and clustering analysis of large-scale biological networks. It is highly interactive and it supports weighted and unweighted multi-edged directed and undirected graphs. It combines a variety of layouts and clustering methods for comprehensive views and advanced data analysis. Its main purpose is to integrate visualization and analysis of heterogeneous data from different sources into a single network. CONCLUSIONS: Medusa provides a concise visual tool, which is helpful for network analysis and interpretation. Medusa is offered both as a standalone application and as an applet written in Java. It can be found at: https://sites.google.com/site/medusa3visualization. PMID- 21978490 TI - Diagnostic potential of circulating cell-free DNA in patients needing mechanical ventilation: promises and challenges. AB - Circulating cell-free DNA (cf-DNA) mainly comes from apoptotic cells and can reflect the extent of cellular damage. Increased plasma levels of cf-DNA have been found in many acute disorders, including septic and clinically ill patients, and usually correlate well with clinical outcome. Acute respiratory failure, the most frequent organ failure in ICU patients, can be related to various acute diseases that may cause cell death and release of DNA into the bloodstream. In a recent issue of Critical Care, Okkonen and colleagues evaluate levels of cf-DNA in plasma as a prognostic marker in patients needing mechanical ventilation. They report that plasma cf-DNA was higher than normal in patients with mechanical ventilation, and even higher in patients who eventually died compared to survivors. However, its usefulness as a death predictor may be limited in the heterogeneous group of mechanically ventilated patients, probably due to confounding effects of co-morbidities, among other factors. PMID- 21978491 TI - Identification and complete genome sequencing of paramyxoviruses in mallard ducks (Anas platyrhynchos) using random access amplification and next generation sequencing technologies. AB - BACKGROUND: During a wildlife screening program for avian influenza A viruses (AIV) and avian paramyxoviruses (APMV) in Belgium, we isolated two hemagglutinating agents from pools of cloacal swabs of wild mallards (Anas platyrhynchos) caught in a single sampling site at two different times. AIV and APMV1 were excluded using hemagglutination inhibition (HI) testing and specific real-time RT-PCR tests. METHODS: To refine the virological identification of APMV2-10 realized by HI subtyping tests and in lack of validated molecular tests for APMV2-10, random access amplification was used in combination with next generation sequencing for the sequence independent identification of the viruses and the determination of their genomes. RESULTS: Three different APMVs were identified. From one pooled sample, the complete genome sequence (15054 nucleotides) of an APMV4 was assembled from the random sequences. From the second pooled sample, the nearly complete genome sequence of an APMV6 (genome size of 16236 nucleotides) was determined, as well as a partial sequence for an APMV4. This APMV4 was closely related but not identical to the APMV4 isolated from the first sample. Although a cross-reactivity with other APMV subtypes did not allow formal identification, the HI subtyping revealed APMV4 and APMV6 in the respective pooled samples but failed to identify the co-infecting APMV4 in the APMV6 infected pool. CONCLUSIONS: These data further contribute to the knowledge about the genetic diversity within the serotypes APMV4 and 6, and confirm the limited sensitivity of the HI subtyping test. Moreover, this study demonstrates the value of a random access nucleic acid amplification method in combination with massive parallel sequencing. Using only a moderate and economical sequencing effort, the characterization and full genome sequencing of APMVs can be obtained, including the identification of viruses in mixed infections. PMID- 21978492 TI - Coexpression of activated c-Met and death receptor 5 predicts better survival in colorectal carcinoma. AB - Dysregulated overexpression of hepatocyte growth factor and its receptor, c-Met, has been reported in various cancers, but its role in colorectal carcinoma (CRC) has not been elucidated. Therefore, we investigated the role of phosphorylated Met (p-Met) in Middle Eastern CRC patient samples and cell lines. The p-Met was overexpressed in 80.8% of CRCs and strongly associated with the expression of p AKT, DR5, and Ki-67 by immunohistochemistry. Coexpression of p-Met and DR5 was seen in 53.1% of CRC cases and was associated with a less aggressive phenotype, characterized by a histological subtype of adenocarcinomas, well-differentiated tumors, and was an independent prognostic marker for better overall survival. PHA665752, a selective p-Met inhibitor, induced apoptosis in CRC cells via inactivation of c-Met and AKT. PHA665752 treatment also caused increased expression of DR5 via generation of reactive oxygen species, and combination treatment with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and PHA665752 induced significant apoptosis. In vivo, cotreatment of a CRC xenograft with PHA665752 and TRAIL significantly reduced tumor volume and weight. These data demonstrate a significant correlation between p-Met and DR5 in patients with CRC. Furthermore, inhibition of p-Met signaling by PHA665752 in combination with TRAIL significantly inhibited cell growth and induced apoptosis in CRC cell lines, suggesting that this may have significant clinical implications as a therapeutic target in the treatment of CRC. PMID- 21978493 TI - Transcriptome profiling characterizes phosphate deficiency effects on carbohydrate metabolism in rice leaves. AB - Phosphorus (P) is a structural component of nucleic acids and phospholipids and plays important roles in plant growth and development. P accumulation was significantly reduced (about 35%) in rice leaves from plants grown under low (32 MUM) P compared to 320 MUM P grown plants. Genome response to low P was examined using the rice 60K oligonucleotide DNA microarrays. At the threshold significance of |log2| fold>2.0, 21,033 genes (about 33.7% of all genes on the microarray) were affected by P deficiency. Among all genes on the microarray, 4271 genes were sorted into 51 metabolic pathways. Low P affected 1494 (35.0%) genes and the largest category of genes was related to sucrose degradation to ethanol and lactate pathway. To survey the role of P in rice, 25 pathways were selected based on number of affected genes. Among these pathways, cytosolic glycolysis contained the least number of upregulated but most down-regulated genes. Low P decreased glucose, pyruvate and chlorophyll, and genes related to carbon metabolism and chlorophyllide a biosynthesis. However, sucrose and starch levels increased. These results indicate that P nutrition affects diverse metabolic pathways mostly related to glucose, pyruvate, sucrose, starch, and chlorophyll a. PMID- 21978494 TI - Targeting alphanubeta3 and alphanubeta5 inhibits photon-induced hypermigration of malignant glioma cells. AB - BACKGROUND: Sublethal photon irradiation was recently suspected to increase tumor cell motility and promote locoregional recurrence of disease. This study was set up to describe mechanisms underlying increased glioma cell migration through photon irradiation and to analyse the modifiability of photon-altered glioma cell motility by integrin inhibition. METHODS: Eight MUm pore size membranes were coated with vitronectin (VN), collagen I and collagen IV. U87 and Ln229 glioma cells were analysed in migration experiments with and without radiotherapy (RT), serum stimulation and addition of monoclonal antibodies directed to human integrins alphanubeta3 and alphanubeta5. Quantitative FACS analysis of integrins was performed in U87 and Ln229 glioma cells following RT. Statistical analysis was performed using Student's t-test. RESULTS: Glioma cell migration is serum dependent and can be increased by photon RT which leads to enhanced expression of Vn receptor integrins. Blocking of either alphanubeta3 or alphanubeta5 integrins by antibodies inhibits Vn-based migration of both untreated and photon-irradiated glioma cells. CONCLUSIONS: Peripheral glioma cells are at risk of attraction into the adjacent healthy brain by serum components leaking through the blood brain barrier (BBB). Radiation therapy is associated with upregulation of Vn receptor integrins and enhanced glioma cell migration at sublethal doses. This effect can be inhibited by specific integrin blockade. Future therapeutical benefit may be derived from pharmacological integrin inhibition in combination with photon irradiation. PMID- 21978496 TI - Low testosterone in ageing men: a modifiable risk factor for frailty? AB - There is substantial interest in the role of testosterone (T) in male ageing. Studies suggest that low T may be a risk factor for frailty, the vulnerable health status that occurs at advanced ages. However, T deficiency is relatively rare in ageing men and, importantly, is linked to modifiable risk factors including body weight and concurrent illnesses. These observations shift the focus away from hormone replacement and towards potential preventative strategies to help maintain T levels in ageing men. Furthermore, the effects of T on physical function remain inconsistent, and studies examining the safety of T treatment in ageing males raise concerns. Further research may usefully focus on novel pro-anabolic pharmaceutical agents, which together with other interventions will allow for optimal management of frailty. PMID- 21978497 TI - A qualitative study exploring women's personal experiences of their perineum after childbirth: expectations, reality and returning to normality. AB - OBJECTIVE: to explore the feelings, perceptions and experiences of women in relation to their perineum following childbirth in the early postnatal period. DESIGN: a qualitative study using grounded theory. Data were collected using diaries and interviews and analysed using constant comparative method. SETTING: hospital and community setting in the South of England. PARTICIPANTS: women (n=11) aged 20-42 years who had a vaginal birth. FINDINGS: one core category, 'Striving for normality' and five major categories emerged: (1) 'preparing for the unknown', (2) 'experiencing the unexpected', (3) 'adjusting to reality', (4) 'getting back to normal' and (5) 'recovery of self'. 'Striving for normality' was where women wanted to be able to do normal things and feel like their normal selves soon after the birth of their baby. Much of what the women described doing during the early postnatal period was related to achieving this goal. KEY CONCLUSIONS: the initial impact of childbirth on the perineum and surrounding area meant that in the first few postnatal days women largely concentrated on managing the effects of this. The impact however, went beyond the immediacy of coping with bodily functions extending into other daily activities in terms of managing and completing them. Examples of daily living activities in this context include bathing, eating, walking as well as completing household chores. Returning to normal following childbirth is significant for women and successfully achieving daily living activities is part of this process. However, women in this study seemed unprepared for the reality of this experience. IMPLICATIONS FOR PRACTICE: women may be poorly prepared for the impact that perineal pain and discomfort can have on their lives especially related to successfully completing daily living activities in the early postnatal period. Consideration should be given to finding different ways of communicating the impact to women such as in the early postnatal period, rather than during pregnancy. The underpinning philosophy of care for the postnatal period should encapsulate a holistic approach, where physical symptoms of perineal pain and discomfort experienced by women are not tackled in isolation from any psychosocial impact this may also have. PMID- 21978498 TI - [Retrospective studies and therapeutic research]. PMID- 21978495 TI - Leptin action in pubertal development: recent advances and unanswered questions. AB - In recent years we have witnessed a considerable advance in the understanding of the processes involved in pubertal development. This is partially due to the discovery of the kisspeptin system and its fundamental role in the control of reproductive physiology. In addition, the suspected relationship between increasing rates of childhood obesity and the apparent reduction in the age of puberty onset in girls has generated a growing interest in identifying the mechanisms by which nutrition may influence reproductive maturation. This review will focus on recent data unveiling the sites of leptin action in pubertal development that were generated using novel molecular techniques and genetically engineered mouse models. It will also emphasize areas of contention and the many relevant questions that remain unanswered. PMID- 21978499 TI - [Hyperhomocysteinemia and leg ulcers: A prospective study of 68 patients]. AB - BACKGROUND: Homocysteine is a sulphur-containing amino acid derived from methionine. Hyperhomocysteinaemia is now recognised as an independent risk factor for occlusive arterial disease and thrombotic venous disease. The aim of this study was to determine the prevalence of hyperhomocysteinemia in patients with leg ulcers. PATIENTS AND METHODS: We prospectively investigated hospitalised patients for vascular leg ulcers between March 2008 and June 2009 at two dermatology centres. We collected details of cardiovascular disease and determined nutritional status by means of the MNA score. Fasting blood samples were taken and analyzed for homocysteine, albumin, prealbumin, folic acid, vitamin B12, creatinine and a complete blood count. RESULTS: Sixty-eight patients were enrolled in the study: 48 women and 20 men. Fifty-three percent of patients had venous leg ulcers, 18% had arterial leg ulcers and 20% had leg ulcers of mixed origin. The prevalence of hyperhomocysteinemia was 56%, with no differences according to ulcer type or gender. DISCUSSION: While the prevalence of hyperhomocysteinemia in our population of leg ulcer patients was high, this descriptive study does not allow us to establish any causal link between hyperhomocysteinemia and leg ulcers. Moreover, since the literature indicates that homocysteine-lowering therapy does not reduce cardiovascular and thromboembolic risk, there appears to be little call for further trials on hyperhomocysteinaemia and leg ulcers. PMID- 21978500 TI - [Therapeutic value of moderate-dose oxybutynin in extensive hyperhidrosis]. AB - BACKGROUND: Hyperhidrosis is a functional disorder characterized by increased sweating that can greatly impair quality of life due to psychosocial factors. It is most often localized (underarms, hands, feet) but can also be generalized. In this case, after eliminating an underlying cause, systemic treatment may be proposed. In this retrospective study, we report the benefits and adverse effects of the anticholinergic drug oxybutynin. PATIENTS AND METHODS: All patients treated with oxybutynin between February 2008 and October 2010 for troublesome generalized hyperhidrosis were recruited after ruling out underlying disease. Oxybutynin (Ditropan((r))) was started at a dose of 1.25mg then increased in increments of 1.25mg every 4 days up to the lowest effective dose, which did not exceed 2.5mg three times per day in order to avoid serious adverse effects. After 2 months of treatment, patients were asked to rate their satisfaction on a scale of 0 to 10, as well as degree of efficacy, time to efficacy, type of adverse effects and whether or not treatment was continued. RESULTS: Thirty patients were included in this study: 24 women and 6 men aged 19 to 64 years (mean=33 years). The treatment was rated by 24 patients (80%) as very effective and by three patients (10%) as moderately effective. Three patients (10%) stopped the treatment due to adverse effects such as faintness and ocular accommodation disorders, and for these patients, the degree of satisfaction ranged from 1 to 3/10. For the other 27 patients, satisfaction was 6 to 10 with a median of 8.5. The onset of action was between 10 and 21 days with an average of 15.4 days. Adverse effects were present in 10 of 27 patients (37%) comprising dry mouth, which was well tolerated (grade 1). Mean follow-up was 14.9 months (2 months to 32 months), with two patients being lost to follow-up. DISCUSSION: The treatment of primary extended or generalized hyperhidrosis is not currently codified. Our study shows the efficacy of oxybutynin in this indication at a moderate dose, with good safety. The satisfaction index was high, with 80% of patients considering the drug very effective and for 10% considering it moderately effective. To our knowledge, this is the first retrospective study in a large population. A placebo-controlled study could provide the grounds for a therapeutic consensus concerning a drug widely known for many years in the treatment of extensive hyperhidrosis. PMID- 21978502 TI - [Early guttate leukoderma in Darier's disease in a patient with black skin]. AB - BACKGROUND: The clinical manifestations of Darier's disease are polymorphic and diverse. Guttate leukoderma has been described in around twenty patients with genetically pigmented skin. We report a case of widespread guttate leukoderma several years before the classic signs of Darier's disease in a patient with black skin. CASE REPORT: A 19-year-old woman consulted for characteristic signs of Darier's disease evolving for the previous four years. Examination revealed perifollicular, non-confluent hypopigmented macules and papules in small drop size (1-5mm in diameter) scattered on the trunk, limbs and the jaw and chin. These hypopigmented lesions had been present since the age of six years. Histology of the keratotic papules confirmed the diagnosis of Darier's disease. Histological inspection of a hypopigmented lesion showed hyperkeratosis, acantholysis and a considerable reduction of epidermal melanin pigment. DISCUSSION: Our observation suggests that a guttate leukoderma could be an early sign, readily accessible to dermatologists, in the diagnosis of Darier's disease in black-skinned patients. PMID- 21978501 TI - [Necrotic leg ulcers induced by vitamin K antagonists: five cases]. AB - BACKGROUND: Vitamin K antagonists (VKAs) are widely used in thromboembolic diseases. We report five cases of necrotic leg ulcers having a particularly severe course and in which withdrawal of VKA treatment alone enabled healing. CASE REPORTS: Five patients presented with necrotic leg ulcers clinically evocative of necrotic angiodermatitis or vasculitis. Histological features were variable, including inconstantly inflammatory lesions (leukocytoclastic vasculitis) and microthrombosis. None of the patients had laboratory signs of autoimmune disease. Healing occurred in all patients only after withdrawal of VKA therapy (fluindione or acenocoumarol). Associated vascular diseases included superficial venous, distal arterial insufficiency and postphlebitic disease. In three cases, thrombotic factors were observed: hyperhomocysteinaemia or heterozygous Factor V Leiden mutation. DISCUSSION: Although the causative role of VKAs is based solely on chronological criteria, this potential side effect deserves publication because of its practical therapeutic consequences. The physiopathological mechanisms accounting for the role of VKAs, including immunoallergic phenomena and, above all, microcirculatory thrombotic processes, are hypothetical and not universally accepted. PMID- 21978503 TI - [Tripe palms and a hypertrophic osteoarthropathy syndrome revealing a neuroendocrine carcinoma of the lung]. AB - BACKGROUND: Tripe palms is a rare cutaneous paraneoplastic syndrome, primarily evocative of lung and gastric neoplasia. Association of many paraneoplastic diseases has also been reported. PATIENTS AND METHODS: A 49-year-old man with a history of alcoholism and smoking addiction reported haemoptysis and thoracic pains present for one year. The physical examination showed left lung condensation. The skin examination revealed a thickened yellowish keratoderma with exaggerated skin ridges and digital clubbing. A diagnosis of paraneoplastic tripe palms was made, prompting repetition of the biopsy which ultimately revealed a neuroendocrine carcinoma. Skeletal scintigraphy showed periosteal proliferation with hypertrophic osteoarthropathy. COMMENTS: "Tripe palms" or "osteoarthritic acanthosis" is a paraneoplastic syndrome. It involves an acquired keratoderma taking on a yellow velvety appearance with accentuation of dermatoglyphic lines. Malignancy is discovered in over 90% of individuals with tripe palms. If malignancy is isolated, it mostly involves the lung (53%). Gastric cancer is associated in 77% of cases if the condition is associated with acanthosis nigricans. In approximately one third of cases, the keratoderma may resolve, generally after treatment of the tumour. The association of many paraneoplastic syndromes has also been reported, in particular digital clubbing and hypertrophic osteoarthropathy. At least 90% of cases of hypertrophic osteoarthropathy in adults occur in patients who have or will eventually develop a malignancy. It is characterized by periostosis of long bones, joint pain, and clubbing, and it is often seen on bone scintigraphy during staging of lung carcinoma. PMID- 21978504 TI - [Neutrophilic dermatosis of the hands]. AB - BACKGROUND: In 1964, based on eight cases, R. Sweet described a form of "acute febrile neutrophilic dermatosis" that was quickly renamed Sweet's syndrome. Over time, other entities (pyoderma gangrenosum, erythema elevatum diutinum, etc.) came to be included in the same nosological group, giving rise to the concept of neutrophilic dermatosis. In addition to types of passage between these different diseases, neutrophilic dermatoses may have a variety of atypical presentations such as that described as "neutrophilic dermatosis of the hands", of which we present a case herein. PATIENTS AND METHODS: A 60-year-old woman with non-insulin dependent diabetes and mild psoriasis was consulting for an eruption mainly on the hands. The lesions, of various shapes, comprised pustules and large bullous lesions on purple oedematous skin; these were painful and some were progressing to ulceration. They measured between 0.5 and 3 cm and were filled with an opaque liquid. These lesions were painful and some were progressing towards ulceration. The patient was also presenting inflammatory joint pain. The histopathology study revealed infiltration of the dermis, predominantly by neutrophils. A diagnosis of neutrophilic dermatosis was made without any clearly discernible distinction between Sweet's syndrome, palmoplantar pustulosis or pyoderma gangrenosum. DISCUSSION: Since the initial description of Sweet's syndrome in 1964, many unusual cases have been described in the literature (associated with neoplasias or systemic diseases, concomitant pustular or bullous lesions, etc.). In 1995, Strutton et al. described a new entity, pustular vasculitis of the hands, based on six cases, which is fairly similar to the present case. Understanding of this syndrome developed and Gallaria renamed it neutrophilic dermatosis of the dorsal hands. Walling and Duquia termed this form of dermatosis palmoplantar Sweet syndrome. CONCLUSION: This case highlights the difficulties in clearly distinguishing forms of neutrophilic dermatosis, adding to the notion of a continuum in neutrophilic disease. PMID- 21978505 TI - [Eruptive naevi associated with octreotide treatment]. AB - BACKGROUND: Octreotide is a synthetic octapeptide having properties related to those of natural somatostatin, a hypothalamic hormone. We report a case of eruptive naevus in patients treated with octreotide. PATIENTS AND METHODS: A 52 year-old man consulted for multiple achromic naevi of recent onset. He was undergoing treatment with octreotide 30 mg per month for hepatic metastases in a setting of operated colonic carcinoid tumor. Since the start of this treatment, he had presented an efflorescence of diffuse naevus comprising over 200 lesions, certain of which were highly atypical. Annual follow-up was carried out. Ten years later, the patient was still alive and undergoing octreotide therapy at the same dose. The number of naevi had stabilized and there was no evidence of melanoma. DISCUSSION: Eruptions of naevi are rare; they may occur at the sites of lesions in bullous diseases or during immunodepression (malignant or drug induced, HIV infection). There are questions concerning possible stimulation of naevus cells and the risk of onset of melanoma. Routine monitoring of pigmented lesions is thus necessary in patients treated with octreotide. PMID- 21978506 TI - [Lipoatrophic panniculitis in adults: treatment with hydroxychloroquine]. AB - BACKGROUND: Lipoatrophic panniculitis is generally considered to be a rare disease affecting children. We report a case involving this condition in an adult patient presenting with striking clinical features and responding to hydroxychloroquine therapy. We discuss the nosological relationship between lipoatrophic panniculitis and connective tissue panniculitis. PATIENTS AND METHODS: A 62-year-old woman was referred to our institution with a six-month history of painful erythematous nodules and plaques on the calves, thighs, buttocks, breasts, abdomen and arms. With each outbreak of new lesions, she felt unwell and experienced fever, chills and sweating. After a few weeks, the lesions progressed circumferentially and led to large areas of subcutaneous atrophy showing a central depression covered with a yellowish, supple skin and surrounded by an annular, infiltrated, erythematous and tender inflammatory margin. Deep subcutaneous biopsy specimens showed typical features of lobular and septal lipophagic panniculitis, with a dense inflammatory infiltrate composed of large histiocytes, multinucleated giant cells and few neutrophils, without vasculitis. The patient was started on hydroxychloroquine 400 mg daily. Three weeks later, her pain and tenderness had completely resolved and the inflammatory margin of the lesions had clearly regressed. DISCUSSION: This unique condition, with distinctive clinical and histological features, is similar to cases described under the term "lipophagic panniculitis", seen mostly in children, but also "connective tissue panniculitis". Their clinical resemblance and response to hydroxychloroquine therapy leads us to think that these two entities, previously subsumed under the eponym of Weber-Christian disease or Rothman-Makai syndrome, are closely related. CONCLUSION: Dermatologists and dermatopathologists should be made aware of this unusual entity, and of the fact that it can arise in adult patients, so that they may make an early diagnosis and thus prevent the unsightly consequences of lipoatrophy. PMID- 21978507 TI - [Significant improvement in ulcerative necrobiosis lipoidica with doxycycline]. PMID- 21978508 TI - [Special beds for palliative care in a dermatology department]. PMID- 21978509 TI - [Atypical fibroplasias due to decubitus: a disease of interest to dermatologists]. PMID- 21978510 TI - [Pain management in Stevens-Johnson syndrome, toxic epidermal necrolysis and other blistering diseases]. PMID- 21978511 TI - [Port-wine stains of the limbs]. PMID- 21978512 TI - [Follicular mucinosis]. PMID- 21978513 TI - [Recessive dystrophic bullous epidermolysis: Is the etiological treatment at the streetcorner?]. PMID- 21978514 TI - [Adams-Oliver syndrome]. PMID- 21978515 TI - [Chronic familial lichenoid keratosis]. PMID- 21978516 TI - [Risk of pellagroid dermatitis during a ketogenic diet in an epileptic patient]. PMID- 21978517 TI - [Pristinamycin and anaphylactic reaction]. PMID- 21978518 TI - Disc height and motion patterns in the lumbar spine in patients operated with total disc replacement or fusion for discogenic back pain. Results from a randomized controlled trial. AB - BACKGROUND CONTEXT: Fusion is considered the "gold standard" in surgical treatment of degenerated disc disease; the intended postoperative goal is absence of mobility, but treatment may induce degeneration in adjacent segments. Total disc replacement (TDR) aims to restore and maintain mobility by replacing a painful disc. Little is known about the degree and quality of mobility in artificial discs in vivo and whether maintained mobility reduces the stress on adjacent segments that is believed to occur after fusion. PURPOSE: To see if surgical goals for respective treatments had been reached, if clinical outcome was related to this, and if differences in disc height at treated segments and adjacent segment motion patterns between groups occurred. STUDY DESIGN: Comparison of X-ray measurements in a randomized controlled trial between instrumented posterior fusion and TDR for chronic low back pain (CLBP) assumed to be discogenic. Results were compared with clinical outcome. PATIENT SAMPLE: The material consisted of 152 patients suffering from CLBP assumed to be discogenic. Seventy-two patients were treated with fusion and 80 with TDR. OUTCOME MEASURES: Results of X-ray measurements were compared between groups and related to self reported clinical results regarding back pain and disability. METHODS: Flexion extension X-rays were analyzed preoperatively and 2 years postoperatively using distortion-compensated Roentgen analysis (DCRA) at treated and adjacent levels, and mobility after fusion and TDR was estimated. Changes in disc height and range of motion (ROM) respective translation in adjacent segments were compared between groups. Results of DCRA measurements were also compared with the clinical outcome. RESULTS: Preoperative flexion-extension ROM was similar between the fusion and TDR groups, and preoperative disc heights of segments to be treated were between one and two standard deviation less than that previously established in a normative database. Seventy percent of fused patients had no mobility, whereas 85% of TDR patients were mobile. Fulfillment of surgical goals was correlated to neither back pain nor disability. Fused segments were lower and TDR segments were higher than normative values postoperatively. There were also significant differences at adjacent segments, there being more translation and flexion-extension in the fusion group than in the TDR group. CONCLUSIONS: This very accurate X-ray method (DCRA) indicates that surgical goals were reached in most patients. This, however, was not correlated to clinical outcome. Differences between the groups in postoperative disc height at treated segments, respective ROM, and translation at adjacent segments did not affect the clinical outcome after 2 years. PMID- 21978519 TI - Low back pain in the United States: incidence and risk factors for presentation in the emergency setting. AB - BACKGROUND CONTEXT: Low back pain is prevalent in the United States. At the present time, no large longitudinal study is available characterizing the incidence of this condition in the US population or identifying potential risk factors for its development. PURPOSE: To characterize the incidence of acute low back pain requiring medical evaluation in the emergency department and establish risk factors for its development. STUDY DESIGN: Cross-sectional study. PATIENT SAMPLE: United States population estimates. OUTCOME MEASURES: Incidence rate ratios were calculated to determine the influence of age, sex, and race on the development of low back pain requiring emergent medical evaluation. METHODS: The National Electronic Injury Surveillance System was queried for all cases of low back pain presenting to emergency departments between 2004 and 2008. Incidence rate ratios were then calculated with respect to age, sex, and race. The chi square statistic was used to identify statistically significant differences in the incidence of low back pain requiring emergent medical evaluation between subgroups. RESULTS: An estimated 2.06 million episodes of low back pain occurred among a population at risk of over 1.48 billion person-years for an incidence rate of 1.39 per 1,000 person-years in the United States. Low back pain accounted for 3.15% of all emergency visits. Injuries sustained at home (65%) accounted for most patients presenting with low back pain. Low back pain demonstrates a bimodal distribution with peaks between 25 and 29 years of age (2.58/1,000 person-years) and 95 to 99 years of age (1.47/1,000) without differentiation by underlying etiology. When compared with females, males showed no significant differences in the rates of low back pain. However, when analyzed by 5-year age group, males aged 10 to 49 years and females aged 65 to 94 years had increased risk of low back pain than their opposite sex counterparts. When compared with Asian race, patients of black and white race were found to have significantly higher rates of low back pain. Older patients were found to be at a greater risk of hospital admission for low back pain. CONCLUSION: Age, sex, and race are significant risk factors for the development of low back pain necessitating treatment in an emergency department. PMID- 21978520 TI - Behavioral stress-induced activation of FoxO3a in the cerebral cortex of mice. AB - BACKGROUND: The transcription factor FoxO3a is highly expressed in brain, but little is known about the response of FoxO3a to behavioral stress and its impact in the associated behavioral changes. METHODS: We tested the response of brain FoxO3a in the learned helplessness (LH) paradigm and tested signaling pathways that mediate the response of FoxO3a. RESULTS: A single session of inescapable shocks (IES) in mice reduced FoxO3a phosphorylation at the Akt-regulating serine/threonine residues and induced prolonged nuclear accumulation of FoxO3a in the cerebral cortex, both indicating activation of FoxO3a in brain. The response of FoxO3a is accompanied by a transient inactivation of Akt and a prolonged activation of glycogen synthase kinase-3beta (GSK3beta). Noticeably, FoxO3a formed a protein complex with GSK3beta in the cerebral cortex, and the interaction between the two proteins was stronger in IES-treated mice. Inhibition of glycogen synthase kinase-3 was able to abolish IES-induced LH behavior, disrupt IES-induced GSK3beta-FoxO3a interaction, and reduce nuclear FoxO3a accumulation. In vitro approaches further revealed that the interaction between GSK3beta and FoxO3a was strongest when both were active; FoxO3a was phosphorylated by recombinant GSK3beta; and glycogen synthase kinase-3 inhibitors effectively reduced FoxO3a transcriptional activity. Importantly, IES-induced LH behavior was markedly diminished in FoxO3a-deficient mice that had minimal FoxO3a expression and reduced levels of FoxO3a-inducible genes. CONCLUSIONS: FoxO3a is activated in response to IES by interacting with GSK3beta, and inhibition of GSK3beta or reducing FoxO3a expression promotes resistance to stress-induced behavioral disturbance by disrupting this signaling mechanism. PMID- 21978522 TI - Payment contracts in a preventive health care system: a perspective from operations management. AB - We consider a health care system consisting of two noncooperative parties: a health purchaser (payer) and a health provider, where the interaction between the two parties is governed by a payment contract. We determine the contracts that coordinate the health purchaser-health provider relationship; i.e. the contracts that maximize the population's welfare while allowing each entity to optimize its own objective function. We show that under certain conditions (1) when the number of customers for a preventive medical intervention is verifiable, there exists a gate-keeping contract and a set of concave piecewise linear contracts that coordinate the system, and (2) when the number of customers is not verifiable, there exists a contract of bounded linear form and a set of incentive-feasible concave piecewise linear contracts that coordinate the system. PMID- 21978521 TI - Roles of p75(NTR), long-term depression, and cholinergic transmission in anxiety and acute stress coping. AB - BACKGROUND: Stress is causally associated with anxiety. Although the underlying cellular mechanisms are not well understood, the basal forebrain cholinergic neurons have been implicated in stress response. p75(NTR) is a panneurotrophin receptor expressed almost exclusively in basal forebrain cholinergic neurons in adult brain. This study investigated whether and how p75(NTR), via regulation of the cholinergic system and hippocampal synaptic plasticity, influences stress related behaviors. METHODS: We used a combination of slice electrophysiology, behavioral analyses, pharmacology, in vivo microdialysis, and neuronal activity mapping to assess the role of p75(NTR) in mood and stress-related behaviors and its underlying cellular and molecular mechanisms. RESULTS: We show that acute stress enables hippocampal long-term depression (LTD) in adult wild-type mice but not in mice lacking p75(NTR). The p75(NTR) mutant mice also exhibit two distinct behavioral impairments: baseline anxiety-like behavior and a deficit in coping with and recovering from stressful situations. Blockade of stress-enabled LTD with a GluA2-derived peptide impaired stress recovery without affecting baseline anxiety. Pharmacological manipulations of cholinergic transmission mimicked the p75(NTR) perturbation in both baseline anxiety and responses to acute stress. Finally, we show evidence of misregulated cholinergic signaling in animals with p75(NTR) deletion. CONCLUSIONS: Our results suggest that loss of p75(NTR) leads to changes in hippocampal cholinergic signaling, which may be involved in regulation of stress-enabled hippocampal LTD and in modulating behaviors related to stress and anxiety. PMID- 21978523 TI - State and self investments in health. AB - In this paper we consider how State investments can crowd out or reinforce self investments in health using a theoretical model of insurance and protection. We apply this model to the smoking cessation decision made by individuals diagnosed with a cardiovascular disease using data from the 1998, 2003 and 2006 waves of the Health Survey of England. Prescription of lipid-lowering drugs, which increased substantially over this period, is used as the measure of State investment. Using bivariate and trivariate probit models, we allow for the endogeneity of the doctor's decision to prescribe and offer smoking cessation advice. We find that unobservable characteristics affecting the prescription of drugs are positively correlated with those affecting smoking advice and negatively correlated with those affecting the propensity to quit. Our results indicate that prescription of lipid-lowering drugs to individuals with cardiovascular disease increases the probability of smoking cessation by 20-28 percentage points. PMID- 21978524 TI - Health economic evaluations comparing insulin glargine with NPH insulin in patients with type 1 diabetes: a systematic review. AB - BACKGROUND: Compared to conventional human basal insulin (neutral protamine Hagedorn; NPH) the long-acting analogue insulin glargine (GLA) is associated with a number of advantages regarding metabolic control, hypoglycaemic events and convenience. However, the unit costs of GLA exceed those of NPH. This study aims to systematically review the economic evidence comparing GLA with NPH in basal bolus treatment (intensified conventional therapy; ICT) of type 1 diabetes in order to facilitate informed decision making in clinical practice and health policy. METHODS: A systematic literature search was performed for the period of January 1st 2000 to December 1st 2009 via Embase, Medline, the Cochrane Library, the databases GMS (German Medical Science) and DAHTA (Deutsche Agentur fur Health Technology Assessment), and the abstract books of relevant international scientific congresses. Retrieved studies were reviewed based on predefined inclusion criteria, methodological and quality aspects. In order to allow comparison between studies, currencies were converted using purchasing power parities (PPP). RESULTS: A total of 7 health economic evaluations from 4 different countries fulfilled the predefined criteria: 6 modelling studies, all of them cost-utility analyses, and one claims data analysis with a cost minimisation design. One cost-utility analysis showed dominance of GLA over NPH. The other 5 cost-utility analyses resulted in additional costs per quality adjusted life year (QALY) gained for GLA, ranging from ? 3,859 to ? 57,002 (incremental cost effectiveness ratio; ICER). The cost-minimisation analysis revealed lower annual diabetes-specific costs in favour of NPH from the perspective of the German Statutory Health Insurance (SHI). CONCLUSIONS: The incremental cost-utility-ratios (ICER) show favourable values for GLA with considerable variation. If a willingness-to-pay threshold of L 30,000 (National Institute of Clinical Excellence, UK) is adopted, GLA is cost-effective in 4 of 6 cost utility analyses (CUA) included. Thus insulin glargine (GLA) seems to offer good value for money. Comparability between studies is limited because of methodological and country specific aspects. The results of this review underline that evaluation of insulin therapy should use evidence on efficacy of therapy from information synthesis. The concept of relating utility decrements to fear of hypoglycaemia is a plausible approach but needs further investigation. Also future evaluations of basal-bolus insulin therapy should include costs of consumables such as needles for insulin injection as well as test strips and lancets for blood glucose self monitoring. PMID- 21978528 TI - Surgical approaches to Cushing's disease. PMID- 21978525 TI - Detecting deteriorated vigilance using percentage of eyelid closure time during behavioral maintenance of wakefulness tests. AB - Several researchers have investigated the relation between vigilance and ocular variables such as saccade, slow eye movement, pupil, blink, or eyelid closure. This study was undertaken to find the most effective indicator among these ocular variables for evaluating short-term (1 min) fluctuation of vigilance, and to investigate the ability of the most effective ocular variable for predicting deteriorated vigilance during behavioral maintenance of the wakefulness test (Oxford sleep resistance test: OSLER test). Nine healthy volunteers (two women, 19-30 years old, 23.4+/-3.9 years old) participated in this study. Ocular variables were recorded during the OSLER test at 10 A.M. and 2 P.M. before and after partial sleep deprivation (4h sleep). The periods during the OSLER test were divided into 1 min epochs. Each epoch was classified according to the number of consecutive missed responses. Decreased blink frequency and pupil diameter as well as increased percentage of eyelid closure time (PERCLOS) and slow eye movement were observed as the consecutive missed responses increased. Among these variables, PERCLOS showed the highest ability to detect occurrence of any missed response and three or more consecutive missed responses. Moreover, a missed response seldom occurred (0.2+/-0.2/20 trial/min) when PERCLOS was less than 11.5% per minute. Results suggest that, among the ocular variables, PERCLOS can prevent error or accident caused by low vigilance most effectively. PMID- 21978529 TI - The general social survey-national death index: an innovative new dataset for the social sciences. AB - BACKGROUND: Social epidemiology seeks in part to understand how social factors- ideas, beliefs, attitudes, actions, and social connections--influence health. However, national health datasets have not kept up with the evolving needs of this cutting-edge area in public health. Sociological datasets that do contain such information, in turn, provide limited health information. FINDINGS: Our team has prospectively linked three decades of General Social Survey data to mortality information through 2008 via the National Death Index. In this paper, we describe the sample, the core elements of the dataset, and analytical considerations. CONCLUSIONS: The General Social Survey-National Death Index (GSS-NDI), to be released publicly in October 2011, will help shape the future of social epidemiology and other frontier areas of public health research. PMID- 21978531 TI - Quantification of incidental mediastinal and hilar irradiation delivered during definitive stereotactic body radiation therapy for peripheral non-small cell lung cancer. AB - To determine the amount of incidental radiation dose received by the mediastinal and hilar nodes for patients with non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). Fifty consecutive patients with NSCLC, treated using an SBRT technique, were identified. Of these patients, 38 had a prescription dose of 60 Gy in 20-Gy fractions and were eligible for analysis. For each patient, ipsilateral upper (level 2) and lower (level 4) paratracheal, and hilar (level 10) nodal regions were contoured on the planning computed tomography (CT) images. Using the clinical treatment plan, dose and volume calculations were performed retrospectively for each nodal region. SBRT to upper lobe tumors resulted in an average total ipsilateral mean dose of between 5.2 and 7.8 Gy for the most proximal paratracheal nodal stations (2R and 4R for right upper lobe lesions, 2L and 4L for left upper lobe lesions). SBRT to lower lobe tumors resulted in an average total ipsilateral mean dose of between 15.6 and 21.5 Gy for the most proximal hilar nodal stations (10R for right lower lobe lesions, 10 l for left lower lobe lesions). Doses to more distal nodes were substantially lower than 5 Gy. The often substantial incidental irradiation, delivered during SBRT for peripheral NSCLC of the lower lobes to the most proximal hilar lymph nodes may be therapeutic for low-volume, subclinical nodal disease. Treatment of peripheral upper lobe lung tumors delivers less incidental irradiation to the paratracheal lymph nodes with lower likelihood of therapeutic benefit. PMID- 21978530 TI - Involvement of reactive oxygen species in 2-methoxyestradiol-induced apoptosis in human neuroblastoma cells. AB - Neuroblastoma is the most common extra-cranial solid tumor in children. Despite advances in the treatment of childhood cancer, outcomes for children with advanced-stage neuroblastoma remain poor. Here we reported that 2 methoxyestradiol (2-ME) inhibited the proliferation and induced apoptosis in human neuroblastoma SK-N-SH and SH-SY5Y cells. 2-ME treatment also resulted in the generation of ROS and the loss of mitochondrial membrane potential in SK-N-SH and SH-SY5Y, indicating that 2-ME-induced apoptosis is mediated by ROS. This is supported by the results that have shown that co-treatment with antioxidants, VC, L-GSH and MitoQ(10), decreased 2-ME-induced generation of ROS and the loss of the mitochondrial membrane potential, increased the Bcl-2/Bax ratio, decreased 2-ME induced activation of caspase-9 and caspase-3 and the up-regulation of apoptosis inducing factor (AIF), and prevented 2-ME-induced apoptosis in SK-N-SH and SH SY5Y cells. These results suggested that oxidative stress plays an important role in 2-ME-induced apoptotic death of human neuroblastoma cells. PMID- 21978532 TI - Bolus electron conformal therapy for the treatment of recurrent inflammatory breast cancer: a case report. AB - The treatment of locoregionally recurrent breast cancer in patients who have previously undergone radiation therapy is challenging. Special techniques are often required that both eradicate the disease and minimize the risks of retreatment. We report the case of a patient with an early-stage left breast cancer who developed inflammatory-type recurrence requiring re-irradiation of the chest wall using bolus electron conformal therapy with image-guided treatment delivery. The patient was a 51-year-old woman who had undergone lumpectomy, axillary lymph node dissection, and adjuvant whole-breast radiation therapy for a stage I left breast cancer in June 1998. In March 2009, she presented at our institution with biopsy-proven recurrent inflammatory carcinoma and was aggressively treated with multi-agent chemotherapy followed by mastectomy that left a positive surgical margin. Given the patient's prior irradiation and irregular chest wall anatomy, bolus electron conformal therapy was used to treat her chest wall and draining lymphatics while sparing the underlying soft tissue. The patient still had no evidence of disease 21 months after treatment. Our results indicate that bolus electron conformal therapy is an accessible, effective radiation treatment approach for recurrent breast cancer in patients with irregular chest wall anatomy as a result of surgery. This approach may complement standard techniques used to reduce locoregional recurrence in the postmastectomy setting. PMID- 21978533 TI - Quantitative MAS NMR characterization of the LiMn(1/2)Ni(1/2)O(2) electrode/electrolyte interphase. AB - The conditions in which degradation processes at the positive electrode/electrolyte interface occur are still incompletely understood and traditional surface analytical techniques struggle to characterize and depict accurately interfacial films. In the present work, information on the growth and evolution of the interphases upon storage and cycling as well as their electrochemical consequences are gathered in the case of LiNi(1/2)Mn(1/2)O(2) with commonly used LiPF(6) (1M in EC/DMC) electrolyte. The use of (7)Li, (19)F and (31)P MAS NMR, made quantitative through the implementation of empirical calibration, is combined with transmission electron microscopy (TEM) and electron energy loss spectroscopy (EELS) to probe the elements involved in surface species and to unravel the inhomogenous architecture of the interphase. At room temperature, contact with the electrolyte leads to a covering of the oxide surface first by LiF and lithiated organic species are found on the outer part of the interphase. At 55 degrees C, not only the interphase proceeds in further covering of the surface but also thickens resulting in an increase of 240% of lithiated species and the presence of -POF(2) fluorophosphates. The composition gradient within the interphase depth is also strongly affected by the temperature. In agreement with the electrochemical performance, quantitative NMR surface analyses show that the use of LiBOB-modified electrolyte results in a Li enriched interphase, intrinsically less resistive than the standard LiPF(6)-based interphase, comprised of a mixture of resistive LiF with non lithiated species. PMID- 21978534 TI - Simultaneous analysis of fluoroquinolones and xanthine derivatives in serum by molecularly imprinted matrix solid-phase dispersion coupled with liquid chromatography. AB - A new molecularly imprinted polymer was synthesized using ofloxacin and theophylline as template and methacryclic acid as function monomer and it was employed as a special dispersant of matrix solid-phase dispersion for selective extraction of fluoroquinolones (ofloxacin, ciprofloxacin and enrofloxacin) and xanthine (caffeine and theophylline) from human serum samples. To eliminate the influences of template leaking on quantitative analysis, acetonitrile trifluoracetic acid (99:1, v/v) was used as the template removing solution. By using water and acetonitrile-trifluoracetic acid (99.5:0.5, v/v) as the washing and elution solvent, respectively, satisfactory recoveries and clean enough chromatogram could obtained. Good linearity of all the analytes was observed in a range of 0.35-150 MUg g(-1) with the correlation coefficient (r(2))>=0.9991. The recoveries of spiked human serum samples were in a range of 89.5-104.0% for fluoroquinolones and xanthine derivatives with RSD less than of 5.0%. PMID- 21978535 TI - Oncocytic mucoepidermoid carcinoma with prominent tumour-associated lymphoid proliferation of the submandibular gland. PMID- 21978536 TI - Establishing a TaqMan-based real-time PCR assay for the rapid detection and quantification of the newly emerged duck Tembusu virus. AB - To establish an accurate, rapid, and a quantifiable method for the detection of the newly emerged duck Tembusu virus (DTMUV) that recently caused a widespread infectious disease in ducks in China, we developed a TaqMan-based real-time PCR assay by using E gene-specific primers and a TaqMan probe. This real-time PCR assay was 100 times more sensitive than the conventional PCR. The reproducibility and specificity of the real-time PCR assay were confirmed using plasmids containing E genes or RNAs and DNAs extracted from well-known viruses causing duck diseases. The reliability of this real-time PCR assay was confirmed in 19 of the 24 swab samples, 22 of the 24 tissue samples collected from experimentally infected ducks, as well as 15 of the 21 clinical samples collected from sick ducks since they were verified as DTMUV-positive. The results reveal that the newly established real-time PCR assay might be a useful diagnostic method for epidemiologically investigating and closely observing the newly emerged DTMUV. PMID- 21978537 TI - The mechanism for proton pumping in cytochrome c oxidase from an electrostatic and quantum chemical perspective. AB - The mechanism for proton pumping in cytochrome c oxidase in the respiratory chain, has for decades been one of the main unsolved problems in biochemistry. However, even though several different suggested mechanisms exist, many of the steps in these mechanisms are quite similar and constitute a general consensus framework for discussing proton pumping. When these steps are analyzed, at least three critical gating situations are found, and these points are where the suggested mechanisms in general differ. The requirements for gating are reviewed and analyzed in detail, and a mechanism is suggested, where solutions for all the gating situations are formulated. This mechanism is based on an electrostatic analysis of a kinetic experiment fior the O to E transition. The key component of the mechanism is a positively charged transition state. An electron on heme a opens the gate for proton transfer from the N-side to a pump loading site (PLS). When the negative charge of the electron is compensated by a chemical proton, the positive transition state prevents backflow from the PLS to the N-side at the most critical stage of the pumping process. The mechanism has now been tested by large model DFT calculations, and these calculations give strong support for the suggested mechanism. PMID- 21978538 TI - Defective mitochondrial translation differently affects the live cell dynamics of complex I subunits. AB - Complex I (CI) of the oxidative phosphorylation system is assembled from 45 subunits encoded by both the mitochondrial and nuclear DNA. Defective mitochondrial translation is a major cause of mitochondrial disorders and proper understanding of its mechanisms and consequences is fundamental to rational treatment design. Here, we used a live cell approach to assess its consequences on CI assembly. The approach consisted of fluorescence recovery after photobleaching (FRAP) imaging of the effect of mitochondrial translation inhibition by chloramphenicol (CAP) on the dynamics of AcGFP1-tagged CI subunits NDUFV1, NDUFS3, NDUFA2 and NDUFB6 and assembly factor NDUFAF4. CAP increased the mobile fraction of the subunits, but not NDUFAF4, and decreased the amount of CI, demonstrating that CI is relatively immobile and does not associate with NDUFAF4. CAP increased the recovery kinetics of NDUFV1-AcGFP1 to the same value as obtained with AcGFP1 alone, indicative of the removal of unbound NDUFV1 from the mitochondrial matrix. Conversely, CAP decreased the mobility of NDUFS3-AcGFP1 and, to a lesser extent, NDUFB6-AcGFP1, suggestive of their enrichment in less mobile subassemblies. Little, if any, change in mobility of NDUFA2-AcGFP1 could be detected, suggesting that the dynamics of this accessory subunit of the matrix arm remains unaltered. Finally, CAP increased the mobility of NDUFAF4-AcGFP1, indicative of interaction with a more mobile membrane-bound subassembly. Our results show that the protein interactions of CI subunits and assembly factors are differently altered when mitochondrial translation is defective. PMID- 21978539 TI - [Adenocarcinoma of the lacrimal gland in bilateral retinoblastoma treated with external radiotherapy: a case report]. AB - This clinical case report describes the clinical findings and diagnosis of lacrimal gland adenocarcinoma that developed 20 years after external beam radiotherapy in the treatment of bilateral retinoblastoma. Visual acuity, slit lamp biomicroscopy, fundus color photography, nuclear magnetic resonance, lateral orbitotomy and histological analysis are described. PMID- 21978540 TI - The association between common genetic variant of microRNA-146a and cancer susceptibility. AB - Published data on the association between microRNA-146a (miR-146a) G/C polymorphism and cancer susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 23 studies including 10,585 cases and 12,183 controls were used in the meta analysis. Overall, no significant associations were found between miR-146a G/C polymorphism and cancer risk when all studies pooled into the meta-analysis (GC vs. CC: OR=1.08, 95% CI=0.94-1.24; GG vs. CC: OR=1.13, 95% CI=0.93-1.37; dominant model: OR=1.09, 95% CI=0.94-1.26). In the subgroup analysis by ethnicity, still no significant associations were found. In the subgroup analysis by cancer type, statistically significantly increased risks were found for papillary thyroid carcinoma (GC vs. CC: OR=3.44, 95% CI=1.86-6.34; GG vs. CC: OR=2.20, 95% CI=1.22 3.99; dominant model: OR=2.68, 95% CI=1.48-4.83). In the subgroup analysis by population-based controls or hospital-based controls, no statistically significantly increased risks were found. Despite some limitations, this meta analysis suggests that the miR-146a G allele is a low-penetrant risk factor for papillary thyroid carcinoma development. PMID- 21978541 TI - Mitochondrial DNA alterations of peripheral lymphocytes in acute lymphoblastic leukemia patients undergoing total body irradiation therapy. AB - BACKGROUND: Mitochondrial DNA (mtDNA) alterations, including mtDNA copy number and mtDNA 4977 bp common deletion (CD), are key indicators of irradiation-induced damage. The relationship between total body irradiation (TBI) treatment and mtDNA alterations in vivo, however, has not been postulated yet. The aim of this study is to analyze mtDNA alterations in irradiated human peripheral lymphocytes from acute lymphoblastic leukemia (ALL) patients as well as to take them as predictors for radiation toxicity. METHODS: Peripheral blood lymphocytes were isolated from 26 ALL patients 24 hours after TBI preconditioning (4.5 and 9 Gy, respectively). Extracted DNA was analyzed by real-time PCR method. RESULTS: Average 2.31 times mtDNA and 0.53 fold CD levels were observed after 4.5 Gy exposure compared to their basal levels. 9 Gy TBI produced a greater response of both mtDNA and CD levels than 4.5 Gy. Significant inverse correlation was found between mtDNA content and CD level at 4.5 and 9 Gy (P = 0.037 and 0.048). Moreover, mtDNA content of lymphocytes without irradiation was found to be correlated to age. CONCLUSIONS: mtDNA and CD content may be considered as predictive factors to radiation toxicity. PMID- 21978542 TI - Elevated production of inflammatory mediators including nociceptive chemokines in patients with neck pain: a cross-sectional evaluation. AB - OBJECTIVE: This study investigated whether the production of inflammatory mediators and chemotactic cytokines (chemokines) is altered in patients with chronic and recurrent neck pain (NP). METHODS: Cross-sectional data evaluating blood and serum samples were obtained from 27 NP patients and 13 asymptomatic (control) subjects recruited from a chiropractic outpatient clinic. Cell cultures were activated by lipopolysaccharide (LPS) and phytoheamagglutinin for 24 to 48 hours. The levels of tumor necrosis factor alpha (TNF-alpha), monocyte chemotactic protein 1, also known as CCL2 (CCL2/MCP-1), and macrophage inflammatory protein 1alpha or CCL3 (CCL3/MIP-1alpha) were determined by specific immunoassays. Serum levels of nitric oxide metabolites were evaluated simultaneously, in vanadium III-reduced samples, by Griess reaction. RESULTS: Low levels of constitutive (spontaneous) TNF-alpha production were present in 7 of the 27 cultures from patients with NP. Both LPS-induced TNF-alpha production and inducer (LPS/phytoheamagglutin)-stimulated production of CCL2 were significantly elevated (P = .00) in patients compared with controls. In patients, the constitutive synthesis of CCL3 occurred significantly more frequently (P = .00) and ranged from 30 to more than 2000 pg/mL. Finally, serum levels of nitric oxide were significantly elevated (P = .00) in NP patients. CONCLUSIONS: Production of inflammatory mediators was consistently elevated in NP patients in this study, both in vitro and in vivo, and activation of inflammatory pathways was accompanied by up-regulation of CC chemokine synthesis. This suggests that, in NP patients, CC chemokines may be involved in regulation of local inflammatory response through recruitment of immune cells to the inflamed tissue and exert pronociceptive effects. PMID- 21978543 TI - The relationship between self-rated disability, fear-avoidance beliefs, and nonorganic signs in patients with chronic whiplash-associated disorder. AB - OBJECTIVES: The purpose of this study was to determine the role of standard and novel (cervical) nonorganic signs in patients with chronic whiplash-associated disorder (WAD). METHODS: Chronic WAD I to III patients (>3 months) were recruited from private chiropractic practice in Canada. Subjects completed a Neck Disability Index (NDI), Tampa Scale for Kinesiophobia (TSK), pain visual analog scale, and pain diagram. Clinical and demographic data were also obtained. Nine standard nonorganic pain behavior tests and 4 novel cervical nonorganic simulation signs (C-NOSS) tests were applied. Bivariate correlations were obtained with the Pearson correlation coefficient. Items achieving statistical significance on univariate analysis were loaded in a sequential linear regression analysis. Post hoc analyses were conducted with analysis of variance tests of NDI and TSK scores. RESULTS: Ninety-one subjects were investigated (49 males and 42 females), with a mean age of 41.7 (SD, 14.7) years and a mean duration of 9.4 (SD, 11.2) months. Because mean NDI scores were 57.5 (SD, 17.8) and mean pain scores were 68.3 (SD, 21.0), this sample represents moderate-to-severe WAD. Fair to moderately strong correlations were obtained between the NDI and the TSK, pain visual analog scale and nonorganic symptoms and signs (NOS-9) and C-NOSS scores, but not with "age," "sex," or "duration." The NOS-9 and C-NOSS scores correlated most strongly at 0.70. A multivariate model accounting for 53% of the variance of the NDI scores (P < .001) was obtained with the TSK, pain severity, and NOS-9 scores. There was no significant correlation between C-NOSS and TSK scores. At least 25% of subjects scored either 5 of 9 or 2 of 4 on the NOS-9 and C-NOSS tests, respectively. CONCLUSIONS: Based on the findings of this study, nonorganic signs should be considered in the interpretation of self-rated disability in patients with moderate-to-severe chronic WAD. PMID- 21978544 TI - Ultrasonographic analysis of the neck flexor muscles in patients with chronic neck pain and changes after cervical spine mobilization. AB - OBJECTIVE: The purpose of this study was to analyze changes in the recruitment of the muscles longus colli (Lco) and sternocledomastoid (SCM) as measured by ultrasonography in patients with chronic neck pain before and immediately after a single cervical Maitland's posterior-anterior central mobilization technique. METHODS: This was a cross-sectional, case-control research design study. Ultrasonographic images of Lco and SCM were taken in 31 patients with chronic neck pain and matched controls during the 5 phases of the craniocervical flexion test before and after a Maitland's posterior-anterior central mobilization session at the cervical spine. Changes in muscle thickness during the test were calculated to infer muscle recruitment. Separate analysis of variance models for each muscle was built. RESULTS: Both groups showed increases in Lco and SCM recruitment between phases (F = 7.95, P < .001; F = 21.29, P < .001), with patients with chronic neck pain demonstrating lesser increases for Lco changes in thickness compared with controls, mainly at phase 5 (-0.09, P = .004; 95% confidence interval [CI], 0.03-0.15). After the mobilization, Lco recruitment increased more significantly in patients with chronic neck pain, and previous difference between groups in phase 5 was no longer significant (-0.07, P = .07; 95% CI, -0.14 to 0.01). The SCM recruitment decreased in phase 1 for patients with chronic neck pain (P = .01; 95% CI, -0.06 to -0.01). CONCLUSION: Cervical mobilization appeared to modulate neck muscles function by increasing deep muscle and reducing superficial muscles recruitment. PMID- 21978546 TI - Two HPA axis genes, CRHBP and FKBP5, interact with childhood trauma to increase the risk for suicidal behavior. AB - Childhood trauma is associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation. Both factors increase risk for suicidal behavior. Corticotropin releasing hormone (CRH) regulates the HPA axis and its actions are moderated by a high-affinity binding protein (CRHBP). We hypothesized that CRHBP variation and interaction with childhood trauma might influence suicidal behavior. Moreover, there might be an additive effect with FKPB5, another HPA axis gene previously associated with suicidality in this dataset. African Americans were recruited: 398 treatment seeking patients with substance dependence (90% men; 120 suicide attempters) and 432 non-substance dependent individuals (40% men; 21 suicide attempters). A total of 474 participants (112 suicide attempters) completed the Childhood Trauma Questionnaire (CTQ). Haplotype-tagging SNPs were genotyped across CRHBP and, for completeness, across CRH, CRHR1 and CRHR2. FKBP5 genotypes were available. Three CRHBP SNPs rs6453267, rs7728378 and rs10474485 showed a nominally significant interaction with the continuous CTQ score to predict suicide attempt; rs7728378 remained significant after FDR correction. There was an additive effect with FKBP5: in the group exposed to high trauma, the prevalence of suicide attempt was 0.35-0.30 in carriers of either the FKBP5 rs3800373 major homozygote or the CRHBP rs7728378 major homozygote and 0.58 in carriers of both major homozygotes. Individuals without either major homozygote were resilient to the effects of childhood trauma (suicide attempt prevalence 0.24). Main effects of CRHBP rs6453267 and CRHR1 rs9900679, both unique to African ancestry, were detected. CRHBP variation may predispose, independently and additively, to suicidal behavior in individuals who have experienced childhood trauma. PMID- 21978547 TI - [Gluten-free diet for children]. AB - Children with celiac disease do not share the same risks as adults, and should have an adapted diet and a prolonged follow-up until adulthood. The following indications seem reasonable: in symptomatic children and adults, gluten free diet during several years in children and for the entire life in adults; in children becoming "silent", without any clinical or biological signs of malnutrition, discussion of coming back to normal diet, under the condition a strict follow-up and restarting gluten free diet at age of 25 and/or in case of pregnancy, to prevent the complications of celiac disease in adulthood; prolonged follow-up for adolescents and young adults returned to a "latent" disease. PMID- 21978548 TI - Chronic deep brain stimulation of the lateral habenula nucleus in a rat model of depression. AB - In the present study, we aim to determine the antidepressant effects of chronic deep brain stimulation (DBS) of the lateral habenula nucleus (LHb) in a rat model of depression and to explore the potential mechanism of DBS induced improvement of depressive symptoms. To establish the rat depression model, animals were repeatedly exposed to a set of chronic mild stressors for four consecutive weeks. The open-field and sucrose consumption tests were used as measures of depression. For DBS treatment, rats were stereotaxically implanted with electrodes into the LHb and stimulated over a course of 28 d. A separate positive control group was given pharmacotherapy with clomipramine hydrochloride. Open-field testing was used to determine behavioral changes following DBS treatment. Monoamine concentrations in blood and brain tissues were determined by fluorescence spectrophotometry. This study demonstrates that DBS of the LHb region significantly improved depressive-like symptoms in the rat model. These improvements manifested as elevated numbers of crossings and rearings during the open-field test in DBS-treated depressed rats compared to controls. In addition, concentrations of monoamines including norepinephrine (NE), dopamine (DA), and serotonin (5-HT) in blood serum and brain tissues were also increased by DBS of the LHb. Therefore, significant improvements in all outcomes were detected following chronic DBS treatment. These results indicate that long-term DBS treatment of the LHb region effectively improved depressive symptoms in rats, likely as a result of elevated monoamine levels. LHb DBS may therefore provide a valuable therapeutic strategy for the clinical treatment of depression. PMID- 21978545 TI - RACK1, A multifaceted scaffolding protein: Structure and function. AB - The Receptor for Activated C Kinase 1 (RACK1) is a member of the tryptophan aspartate repeat (WD-repeat) family of proteins and shares significant homology to the beta subunit of G-proteins (Gbeta). RACK1 adopts a seven-bladed beta propeller structure which facilitates protein binding. RACK1 has a significant role to play in shuttling proteins around the cell, anchoring proteins at particular locations and in stabilising protein activity. It interacts with the ribosomal machinery, with several cell surface receptors and with proteins in the nucleus. As a result, RACK1 is a key mediator of various pathways and contributes to numerous aspects of cellular function. Here, we discuss RACK1 gene and structure and its role in specific signaling pathways, and address how posttranslational modifications facilitate subcellular location and translocation of RACK1. This review condenses several recent studies suggesting a role for RACK1 in physiological processes such as development, cell migration, central nervous system (CN) function and circadian rhythm as well as reviewing the role of RACK1 in disease. PMID- 21978549 TI - Neuroprotection against excitotoxic and ischemic insults by bis(12)-hupyridone, a novel anti-acetylcholinesterase dimer, possibly via acting on multiple targets. AB - The activation of N-methyl-d-aspartate (NMDA) receptors by excessive release of glutamate is involved in the pathogenesis of ischemic stroke. Thus the NMDA receptor has become an attractive therapeutic target for the development of neuroprotectants, especially from antagonists with moderate to low affinity. In the current study, NMDA receptor blockage and neuroprotective effects of bis(12) hupyridone (B12H), a novel dimeric acetylcholinesterase inhibitor derived from a naturally occurring monomeric analog huperzine A, were investigated in vitro and in vivo. In primary rat cerebellar granule neurons, B12H (0.1 nM to 1 MUM) prevented glutamate-induced apoptosis in a concentration- and time-dependent manner. Receptor-ligand binding analysis showed that B12H competed with [(3)H]MK801 with a K(i) value of 7.7 MUM. In the 2-hour middle cerebral artery occlusion rat model, B12H (0.4 and 0.8 mg/kg, 30 min before-ischemia and 15 min post-ischemia, i.p.) significantly attenuated ischemia-induced apoptosis in the penumbra region, improved neurological behavior impairment, and decreased cerebral infarct volume, cerebral edema and neuronal apoptosis in the stroke model. Together, these results showed that B12H moderately blocks NMDA receptors at MK801 site and exerts neuroprotection against excitotoxic and ischemic insults in vitro and in vivo. Combined with our previous publications, we conjecture that B12H might exert neuroprotection via acting on multiple targets. PMID- 21978550 TI - Evaluation of voxel-based group-level analysis of diffusion tensor images using simulated brain lesions. AB - We simulated brain lesions in mean diffusivity (MD) and fractional anisotropy (FA) images of healthy subjects to evaluate the performance of voxel-based analysis (VBA) with SPM2. We increased MD and decreased FA, simulating the most typical abnormalities in brain pathologies, in the superior longitudinal fasciculus (SLF), corticospinal tract (CST), and corpus callosum (CC). Lesion sizes varied from 10 to 400 voxels (10.5 mm3 each) and intensity changes from 10 to 100%. The VBA contained eddy current correction, spatial normalization, smoothing, and statistical analysis. The preprocessing steps changed the intensities of MD and FA lesions from the original values, and many lesions remained undetected. The detection thresholds varied between the three brain areas, and between MD and FA images. Although spatial smoothing often improved the sensitivity, it also markedly enlarged the estimated lesion sizes. Since conventional VBA preprocessing significantly affected the outcome and sensitivity of the method itself, the impact of analysis steps should be verified and considered before interpreting the findings. Our results provide insight into the sizes and intensity changes of lesions that can be detected with VBA applied to diffusion tensor imaging (DTI) data. PMID- 21978551 TI - Acetylcholinesterase activity in the brain of dystonia musculorum (Dst(dt-J)) mutant mice. AB - The dystonia musculorum (Dst(dt-J)) mutant mouse suffers from severe motor coordination deficits, characterized, among various symptoms, by a spastic ataxia and dystonic movements, indicating central defects in motor structures in addition to dystrophy of peripheral sensory tracts and partial degeneration of spinocerebellar tracts. Neurochemical alterations, notably in dopaminergic and noradrenergic systems, were previously observed in basal ganglia and cerebellum. A quantitative histochemical cartography of brain acetylcholinesterase activity in Dst(dt-J) mutants, in comparison with controls, revealed increases in the neostriatum, the habenula-interpeduncular pathway, the cholinergic pedunculopontine nucleus and its target structures, the thalamus, major regions of the basal ganglia, such as substantia nigra, ventral tegmental area, globus pallidum, and subthalamic nucleus, as well as in associated extrapyramidal regions, such as red nucleus, brainstem reticular formation, and superior colliculus. These acetylcholinesterase changes may play a role in motor deficits, particularly the dystonic symptomatology observed in the mutation. PMID- 21978552 TI - Durable antibacterial and cross-linking cotton with colloidal silver nanoparticles and butane tetracarboxylic acid without yellowing. AB - Colloidal nano silver was applied on the surface of cotton fabric and stabilized using 1,2,3,4-butanetetracarboxylic acid (BTCA). The two properties of antimicrobial activity and resistance against creasing were imparted to the samples of fabric as a result of the treatment with silver nano colloid and BTCA. The antimicrobial property of samples was evaluated using two pathogenic bacteria including Escherichia coli and Staphylococcus aureus as outstanding barometers in this field. The durability of applied nanoparticles, color variation, wettability and wrinkle recovery angle of the treated samples were investigated employing related credible standards. The presence of nano silver particles on the surface of treated cotton fabric was proved using EDS spectrum as well as the SEM images. Furthermore, the creation of cross-links was confirmed by the means of both ATR FTIR and Raman spectra. In conclusion, it was observed that BTCA plays a prominent role in stabilizing silver nanoparticle. Besides, Wettability and winkle recovery angle of finished samples decreased and increased, respectively. In addition, it is noteworthy that no obvious color variation was observed. PMID- 21978553 TI - Synthesis, characterizations of dye-doped silica nanoparticles and their application in labeling cells. AB - Spherical silica nanoparticles coated with fluorescein isothiocyanate (FITC) dyes were prepared by using an improved Stober method. The nanoparticles were ~55 nm in diameter and were essentially mono-dispersed in aqueous solutions. The fluorescence excitation and emission spectra of the nano-composite particles showed no obvious shift compared with that of the free FITC in the aqueous solution. The photostability of FITC doped SiO(2) nanoparticles (FDSN) increased about three-fold, compared to the free FITC in the solution. The fluorescence of FDSN was tested as imaging tools using a confocal laser scanning microscope (CLSM). From the non-small cell lung cancer (NSCLC) uptake of FDSN, it was concluded that the FDSN were incorporated into these cells. The cytotoxicity assay and the NSCLC uptake of FDSN over time were also investigated in this work. PMID- 21978554 TI - Atomic force microscopy studies of the influence of convex and concave nanostructures on the adsorption of fibronectin. AB - Atomic force microscopy (AFM)-based force spectroscopy was used to analyze the adsorption of bovine plasma fibronectin on periodically grooved nanostructures (groove/summit width: 90 nm; depth: 120 nm). We present a simple procedure that allowed us to directly compare the local protein density and conformation for the convex summits, the concave grooves and planar reference regions of the substrate. At a bulk fibronectin concentration of 5 MUg/ml, the amount of adsorbed protein per surface area was significantly higher in all regions of the nanostructure than on the planar reference, and fibronectin tended to adsorb preferentially in the concave grooves. The increased surface concentration resulted in an additional stabilization of the molecules by protein-protein interactions and a lower degree of denaturized fibronectin in the nanostructured regions. The stabilization was less pronounced in concave regions, indicating that the increased contact area in the grooves counteracted the stabilization by increased protein-substrate interactions and must be compensated for by additional protein-protein interactions. Less favorable sites were occupied at higher bulk fibronectin concentrations (25 MUg/ml, 100 MUg/ml), and a high degree of native folded fibronectin was observed in both the nanostructured and planar regions. Our results demonstrate that the amount of adsorbed fibronectin per surface area can be increased if a substrate is provided with a topographic nanostructure. Our results also show that the local conformational state of fibronectin is determined by the locally different interplay of protein-protein and protein-substrate interactions. PMID- 21978555 TI - Novel hydrogel particles and their IPN films as drug delivery systems with antibacterial properties. AB - Poly(acrylonitrile) (p(AN))-based materials such poly(acrylonitrile-co-(3 acrylamidopropyl)-trimethylammonium chloride (p(AN-co-APTMACl)), poly(acrylonitrile-co-4-viniyl pyridine) (p(AN-co-4-VP)) and poly(acrylonitrile co-N-isopropylacrylamide) (p(AN-co-NIPAM)) core-shell nanoparticles were prepared. The core materials, AN, in p(AN-co-4-VP) nanoparticles, were amidoximated and the shell materials, 4-VP, were quaternized to generate p(AN-co 4-VP)(+) and p(AN-co-4-VP)(++), single and double positively charged core-shell nanoparticles, respectively. Furthermore, interpenetrating microgels-hydrogel (IPN) polymeric networks were prepared by mixing double quaternized p(AN-co-4 VP)(++) core-shell particles with acrylamide (AAm) and 2-hydroxyethylmethacrylate (HEMA) before polymerization. A model drug, fluorescein sodium salt (FSS) was used in absorption/release studies from these IPNs. Moreover, the prepared and chemically modified particles were tested against Staphylococcus aureus ATCC6538, Pseduomonas aeruginosa ATCC9027, Bacillus subtilis ATCC6633, and Escherichia coli ATCC8739, and found that some of these particles had antibacterial properties against tested bacteria. PMID- 21978556 TI - Patterned domains of supported phospholipid bilayer using microcontact printing of Pll-g-PEG molecules. AB - In this work, we propose a reliable microcontact printing (MUCP) process for generating Patterned Supported Phospholipids Bilayer (P-SPB) confined by Poly-L (lysine)-grafted-polyethylene(glycol) (Pll-g-PEG) molecular barriers. The efficiency of Pll-g-PEG for inhibiting the fusion process of incubated liposome was first analyzed by Quartz Micro Balance (QCM) measurements. The quality and stability of Pll-g-PEG patterns were then both verified by fluorescence microscopy and Atomic Force Microscopy (AFM) in liquid media. The micro domains of P-SPB produced were stable in liquid environment during several weeks and also during AFM imaging. This exceptional stability is a clear improvement compared to previous studies involving proteins as confinement barriers. PMID- 21978558 TI - Spectroscopic characterization, X-ray structure, antimicrobial activity and DFT calculations of novel dipicolinate copper(II) complex with 2,6 pyridinedimethanol. AB - Novel dipicolinate complex of copper(II) ion, [Cu(dmp)(dpc)].0.8H(2)O [dmp: 2,6 pyridinedimethanol; dpc: dipicolinate or pyridine-2,6-dicarboxylate], has been prepared and fully characterized by single crystal X-ray structure determination. The central copper(II) ion is bonded to dpc and dmp ligands through pyridine nitrogen atom together with two oxygen atom, forming the distorted octahedral geometry. The complex molecules, connected via O-H...O hydrogen bonds, form a supramolecular structure. H(2)dpc, [Cu(dpc)(H(2)O)(3)] and [Cu(dmp)(dpc)].0.8H(2)O were screened for antimicrobial activity against Gram positive, Gram-negative bacteria and yeast. H(2)dpc and [Cu(dpc)(H(2)O)(3)] exhibited antibacterial and antifungal activity, while [Cu(dmp)(dpc)].0.8H(2)O exhibited activity only for Gram-positive bacteria. The geometry optimization and EPR parameters were carried out using the following unrestricted hybrid density functionals: LSDA, BPV86, B3LYP, B3PW91, MPW1PW91, PBEPBE and HCTH. Although the supramolecular interactions have some influences on the molecular geometry in solid state phase, calculated data show that the predicted geometries can reproduce the structural parameters. The electronic station in the frontier orbitals of the copper complex calculated from the experimental data is compared to the results of time-depended DFT calculations with the polarizable continuum model. Calculated vibrational frequencies are consistent with the experimental IR data. PMID- 21978557 TI - The curse of the prey: Sarcoptes mite molecular analysis reveals potential prey to-predator parasitic infestation in wild animals from Masai Mara, Kenya. AB - BACKGROUND: Recently, there have been attempts to understand the molecular epidemiology of Sarcoptes scabiei, to evaluate the gene flow between isolates of S. scabiei from different hosts and geographic regions. However, to our knowledge, a molecular study has not been carried out to assess the molecular diversity and gene flow of Sarcoptes mite in a predator/prey ecosystem. RESULTS: Our study revealed an absence of gene flow between the two herbivore (Thomson's gazelle and wildebeest)- and between the two carnivore (lion and cheetah)-derived Sarcoptes populations from Masai Mara (Kenya), which is in discrepancy with the host-taxon law described for wild animals in Europe. Lion- and wildebeest-derived Sarcoptes mite populations were similar yet different from the Thomson's gazelle derived Sarcoptes population. This could be attributed to Sarcoptes cross infestation from wildebeest ("favourite prey") of the lion, but not from Thomson's gazelle. The cheetah-derived Sarcoptes population had different subpopulations: one is cheetah-private, one similar to the wildebeest- and lion derived Sarcoptes populations, and another similar to the Thomson's gazelle derived Sarcoptes mite population, where both wildebeest and Thomson's gazelle are "favourite preys" for the cheetah. CONCLUSIONS: In a predator/prey ecosystem, like Masai Mara in Kenya, it seems that Sarcoptes infestation in wild animals is prey-to-predator-wise, depending on the predator's "favourite prey". More studies on the lion and cheetah diet and behaviour could be of great help to clarify the addressed hypotheses. This study could have further ramification in the epidemiological studies and the monitoring protocols of the neglected Sarcoptes mite in predator/prey ecosystems. PMID- 21978559 TI - Development of an reliable analytical method for synergistic extractive spectrophotometric determination of cobalt(II) from alloys and nano composite samples by using chromogenic chelating ligand. AB - A synergistic simple and selective spectrophotometric method was developed for the determination of cobalt(II) with 1-(2',4'-dinitro aminophenyl)-4,4,6 trimethyl-1,4-dihydropyrimidine-2-thiol [2',4'-dinitro APTPT] as a chromogenic reagent. The proposed method has been described on the basis of synergistic effective extraction of cobalt(II) in presence of pyridine at pH range 9.5-10.2, showed orange-red coloured ternary complex having molar ratio 1:2:2 (M:L:Py). The equilibrium time is 10 min for extraction of cobalt(III) from organic phase. The absorbance of coloured organic layer in chloroform is measured spectrophotometrically at 490 nm against reagent blank. The Beer's law was obeyed in the concentration range 2.5-15 MUg mL(-1) of cobalt(II) and optimum concentration range was 5-12.5 MUg mL(-1) of cobalt(II) and it was evaluated from Ringbom's plot. The molar absorptivity and Sandell's sensitivity of cobalt(II) 2',4'-dinitro APTPT-pyridine complex in chloroform are 1.109*10(3) L mol(-1) cm( 1) and 0.053 MUg cm(-2), respectively while molar absorptivity and Sandell's sensitivity of cobalt(II)-2',4'-dinitro APTPT complex in chloroform are 6.22*10(2) L mol(-1) cm(-1) and 0.096 MUg cm(-2), respectively. The composition of cobalt(II)-2',4'-dinitro APTPT-pyridine complex (1:2:2) was established by slope ratio method, mole ratio method and Job's method of continuous variation. The ternary complex was stable for more than 48 h. The interfering effects of various cations and anions were also studied, and use of suitable masking agents enhances the selectivity of the method. The method is successfully applied for the determination of cobalt(II) in binary, synthetic mixtures and real samples. A repetition of the method was checked by finding relative standard deviation (R.S.D.) for n=5 which was 0.15%. The reliability of the method is confirmed by comparison of experimental results with atomic absorption spectrophotometer. PMID- 21978560 TI - Synthesis, growth, thermal, optical and mechanical properties of 2 Aminopyridinium 4-methylbenzoate Dihydrate. AB - Organic NLO material of 2-Aminopyridinium 4-methylbenzoate Dihydrate (2A4M) was synthesized using 2-Aminopyridinium and 4-methylbenzoic acid as starting materials. Single crystals of 2A4M were grown by the slow evaporation solution growth technique at room temperature using water as a solvent. The grown crystal was characterized by single crystal XRD to confirm the crystal system and lattice parameters. From the optical studies the optical band gap and the refractive index of the material are found to be 2.9 eV and 1.40 at 1200 nm. Functional groups of the crystallised material were confirmed by FTIR vibrational spectrum. Thermal behaviour of the title compound was studied using thermogravimetric (TG) and differential thermal analyses (DTA). The initial weight loss is found up to 125 degrees C, which corresponds to 13.2% i.e. presence of 2 mole of water in the lattice. The grown crystal was subjected to Vickers hardness test and the brittleness index, fracture toughness, yield strength were estimated. The etching studies reveal the growth pattern and dislocations present in the grown crystal. The second harmonic generation (SHG) behaviour of 2A4M was tested by Kurtz-Perry powder technique. The relative SHG efficiency of 2A4M is found to be 3.03 times that of the reference material KDP. PMID- 21978561 TI - Spectroscopic studies on some fluorescent mixed-ligand titanium(IV) complexes. AB - A novel route to synthesize some titanium(IV) complexes containing acetylacetone, straight chain carboxylic acid and hydroxycarboxylic acid ligands has been investigated. Complexes with the general formula [Ti(acac)Cl(2 n)(OOCR*)(n)(OOCC(15)H(31))] (where Hacac=acetylacetone, R*COOH=hydroxycarboxylic acids and n=1 or 2) have been isolated and characterized. Molecular weight determinations indicated mononuclear nature of the complexes. LMCT bands were observed in the electronic spectra. Infrared spectra suggested bidentate nature of the ligands. Fluorescent behaviour of the complexes was noticed on the basis of fluorescence spectra. Powder XRD indicated them to be semi-crystalline having the crystallite size in 136-185 nm range. Transmission electron microscopy (TEM) indicated spherical particles of ~ 200 nm diameter. On the basis of physico chemical studies, it is suggested that titanium is having coordination number 7 or 8 in these complexes. PMID- 21978562 TI - Thin hard crest on the edge of ceramic acetabular liners accelerates wear in edge loading. AB - Ceramic acetabular liners may exhibit a small, sharp crest-an artifact of discontinuous machining steps--at the junction between the concave spherical surface and the interior edge. On 3 ceramic liners, this crest was found to form a 9 degrees to 11 degrees deviation from tangency. Edge loading wear tests were conducted directly on this crest and on a smoother region of the edge. The crest elicited 2 to 15 times greater volumetric wear on the femoral head. The propensity of the crest to rapidly (<2000 wear cycles) cause elevated wear under low contact force (200 N) suggests that the crest artifact of prevailing machining protocols might be a root cause of stripe wear and squeaking in ceramic acetabular bearings. PMID- 21978563 TI - Eleven- to 14-year follow-up results of cementless total hip arthroplasty using a third-generation alumina ceramic-on-ceramic bearing. AB - To analyze long-term survivorship of cementless total hip arthroplasties (THAs) with the third-generation alumina ceramic-on-ceramic bearing, 100 consecutive THAs between 1996 and 1998 were reviewed. One cup and 2 stems were revised due to aseptic loosening. Another cup showed chipping of the acetabular liner at 8 years and required cup revision. The remaining hips showed stable bone ingrowth fixation with no osteolysis at the final follow-up. The 14-year survivorship as the end point of revision was 97.9% for the cup, 97.8% for the stem, and 95.7% for the overall implants, respectively. We conclude that cementless THA with the third-generation ceramic-on-ceramic hip bearing provided an excellent survivorship and eliminated periprosthetic osteolysis for 11 to 14 years. PMID- 21978564 TI - Rotational profile of lower limb and axis for tibial component alignment in varus osteoarthritic knees. AB - The purposes of this study were to describe the changes in tibial torsion and knee rotation in varus osteoarthritic knees and to check the reliability of reference axis, for tibial component placement, based on femoral transepicondylar axis in these patients. A secondary goal was to determine which reference axis based on proximal tibia is most accurate for determining tibial component rotation. Fifty-two varus osteoarthritic knees and 20 normal knees were analyzed using computed tomographic scan. Tibial torsion and knee rotation were significantly reduced in patients with osteoarthritis. Reference axis based on posterior tibial condyles was most accurate and least variable for tibial component alignment. A significant negative correlation was found between knee rotation and tibial axis based on transepicondylar axis (r = -0.485). PMID- 21978565 TI - Bilateral patellar component shear failure of highly cross-linked polyethylene components: report of a case and laboratory analysis of failure mechanisms. AB - A case of bilateral patellar component failure due to fatigue fracture of the all polyethylene fixation pegs in a highly cross-linked ultra-high-molecular-weight polyethylene design is presented. To recreate this failure mode, a novel test method was developed to investigate the effects of peg orientation and cement technique on patella fatigue strength under cyclic compression and shear loading. Patellar peg orientation had a minor effect on shear strength, whereas lack of cement in the backside patellar groove had a substantial effect. The shear fatigue strength exceeded in vivo force estimates when the patellar groove was fully cemented. The test results and retrieval analysis suggest that high activity level and inadequate cement fixation of the patellar component may contribute to all-polyethylene patellar component peg fractures. PMID- 21978566 TI - Scaling digital radiographs for templating in total hip arthroplasty using conventional acetate templates independent of calibration markers. AB - We describe a scaling method for templating digital radiographs using conventional acetate templates independent of template magnification without the need for a calibration marker. The mean magnification factor for the radiology department was determined (119.8%; range, 117%-123.4%). This fixed magnification factor was used to scale the radiographs by the method described. Thirty-two femoral heads on postoperative total hip arthroplasty radiographs were then measured and compared with the actual size. The mean absolute accuracy was within 0.5% of actual head size (range, 0%-3%) with a mean absolute difference of 0.16 mm (range, 0-1 mm; SD, 0.26 mm). Intraclass correlation coefficient showed excellent reliability for both interobserver and intraobserver measurements with intraclass correlation coefficient scores of 0.993 (95% CI, 0.988-0.996) for interobserver measurements and intraobserver measurements ranging between 0.990 and 0.993 (95% CI, 0.980-0.997). PMID- 21978567 TI - Extensor mechanism repair failure with use of bidirectional barbed suture in total knee arthroplasty. AB - Total knee arthroplasty (TKA) continues to advance as innovative devices become available. #2 PDO Quill SRS (Angiotech, Reading, Pa) bidirectional barbed suture was used for 161 primary TKAs at our facility. We report on 3 separate cases of extensor mechanism repair failure after primary TKA in which a barbed suture was used for extensor mechanism closure. Before the implementation of this device, there were no reported failures in 385 primary TKAs. We recommend that surgeons who use this device for extensor mechanism repair of a medial parapatellar arthrotomy in TKA exercise caution when operating on patients with morbid obesity, diabetes, and rheumatoid arthritis. We have discontinued use of the bidirectional barbed suture until more definitive large orthopedic studies establish its efficacy and safety. PMID- 21978568 TI - Intensity-modulated radiotherapy for squamous cell carcinoma of the anal canal: efficacy of a low daily dose to clinically negative regions. AB - BACKGROUND: We aimed to assess outcomes of patients with anal cancer who underwent intensity-modulated radiotherapy (IMRT) and received less than 1.80 Gy/day. METHODS: We retrospectively reviewed our experience using a low fractional dose (< 1.80 Gy) of IMRT to elective nodal areas for patients receiving chemoradiotherapy for anal cancer. Three-year freedom from any disease relapse and overall survival were estimated using Kaplan-Meier curves. We documented the daily dose that was delivered to clinically uninvolved regions and to areas of gross disease. Incidence of regional failures in high (>= 1.80 Gy) and low (< 1.80 Gy) daily dose regions was assessed. RESULTS: Thirty-four consecutive patients (median age, 59 years) received IMRT from June 2005 through January 2009. Median follow-up duration was 22 months. Twenty-eight patients had T1 or T2 disease and 6 had T3 or T4 disease. Fourteen patients had nodal metastases. Median treatment dose was 50.40 Gy (range, 48.60-57.60 Gy) in 25 to 32 fractions. The range of fractional doses to clinically negative volumes was 1.28 to 1.80 Gy. Seventeen patients (50%) received a fractional dose of less than 1.60 Gy, 13 (38%) received less than 1.50 Gy, and 9 (26%) received less than 1.40 Gy to at least a portion of the clinically negative volume. Three-year freedom from relapse was 80%, and 3-year overall survival was 87%. No patient had treatment failure in the clinically negative volume that received a low daily dose. CONCLUSIONS: Our data support using doses between 1.50 and 1.80 Gy/day to clinically uninvolved regions. PMID- 21978569 TI - Occurrence, distribution and fluxes of benzotriazoles along the German large river basins into the North Sea. AB - Benzotriazole (BT) and tolyltriazole (TT) are high production volume chemicals which are used in various industrial and household applications. In this study, the distribution of benzotriazoles in the estuaries of different rivers of central Europe and in the North Sea was analyzed by solid-phase extraction (SPE) and liquid chromatography-mass spectrometry (HPLC-MS/MS). BT as well as TT was detected in all water samples. The concentrations for total benzotriazoles (BTs) ranged from 1.7 to 40 ng/L in the North Sea in costal areas. Concentrations in rivers are from 200 to 1250 ng/L, respectively. The mass flux of total benzotriazoles from the major rivers of central Europe into the North Sea was calculated to 78 t/a, dominated by the Rhine with an individual flux of 57 t/a of BTs. The analysis of the distribution profile in the North Sea showed that the decrease of the concentration was mostly caused by dilution and that the benzotriazoles are poorly degradable in the North Sea. This paper presents the first report of benzotriazoles in the marine environment. PMID- 21978570 TI - A coupled model tree (MT) genetic algorithm (GA) scheme for biofouling assessment in pipelines. AB - A computerized learning algorithm was developed for assessing the extent of biofouling formations on the inner surfaces of water supply pipelines. Four identical pipeline experimental systems with four different types of inlet waters were set up as part of a large cooperative project between academia and industry in Israel on biofouling modeling, prediction, and prevention in pipeline systems. Samples were taken periodically for hydraulic, chemical, and biological analyses. Biofilm sampling was done using Robbins devices, carrying stainless steel coupons. An MT-GA, a hybrid model combining model trees (MTs) and genetic algorithms (GAs) in which the sampled input data are selected by the proposed methodology, was developed. The method outcome is a set of empirical linear rules which form a model tree, iteratively optimized by a GA and verified using the dataset resulting from the empirical field studies. Good correlations were achieved between modeled and observed cell coverage area within the biofilm. Sensitivity analysis was conducted by testing the model's response to changes in: (1) the biofilm measure used as output (target) variable; (2) variability of GA parameters; and (3) input attributes. The proposed methodology provides a new tool for biofouling assessment in pipelines. PMID- 21978571 TI - Non-linear effects on solute transfer between flowing water and a sediment bed. AB - A previously developed model of periodic pore water flow in space and time, and associated solute transport in a stream bed of fine sand is extended to coarse sand and fine gravel. The pore water flow immediately below the sediment/water interface becomes intermittently a non-Darcy flow. The periodic pressure and velocity fluctuations considered are induced by near-bed coherent turbulent motions in the stream flow; they penetrate from the sediment/water interface into the sediment pore system and are described by a wave number (chi) and a period (T) that are given as functions of the shear velocity (U(*)) between the flowing water and the sediment bed. The stream bed has a flat surface without bed forms. The flow field in the sediment pore system is described by the continuity equation and a resistance law that includes both viscous (Darcy) and non-linear (inertial) effects. Simulation results show that non-linear (inertial) effects near the sediment/water interface increase flow resistance and reduce mean flow velocities. Compared to pure Darcy flow, non-linear (inertial) effects reduce solute exchange rates between overlying water and the sediment bed but only by a moderate amount (less than 50%). Turbulent coherent flow structures in the stream flow enhance solute transfer in the pore system of a stream bed compared to pure molecular diffusion, but by much less than standing surface waves or bed forms. PMID- 21978573 TI - Dermatoscopic vascular patterns in cutaneous Merkel cell carcinoma. AB - BACKGROUND: Merkel cell carcinoma (MCC) is one of the most aggressive primary cutaneous malignancies. The clinical diagnosis of MCC is often delayed. Although the rarity of this skin cancer partially explains the low clinical suspicion by physicians, the absence of characteristic clinical features contributes to the delay in diagnosis. Dermatoscopy has proven a useful diagnostic tool in other cutaneous malignancies; however, the dermatoscopic features of cutaneous MCC are unknown. OBJECTIVE: We performed dermatoscopy on 10 primary cutaneous MCC to describe the dermatoscopic features and correlate these findings with the histopathologic parameters. METHODS: Consecutive patients with cutaneous MCC were identified and their tumors were evaluated under dermatoscopy. An 8-point MCC histopathology profile was recorded for each primary tumor in an attempt to correlate individual parameters with dermatoscopic features. RESULTS: All 10 tumors showed an irregular vascular pattern under dermatoscopy and demonstrated milky-red areas/globules and numerous linear irregular vessels. No correlation was noted between dermatoscopic and histopathologic features. LIMITATIONS: The patients were from a single institution and tumors evaluated by a single dermatoscopic reviewer. Because of the rarity of this tumor, a small number of tumors were evaluated (10). CONCLUSION: MCC exhibits a variety of dermatoscopic vascular patterns, most commonly milky-red areas/globules, polymorphous vessels, and linear-irregular vessels. Although we found no specific dermatoscopic pattern for MCC in our series, the polymorphous vascular pattern was atypical and suggestive of a malignant process. Further studies should be done to investigate the potential correlation between dermatoscopic features and histopathologic parameters. PMID- 21978572 TI - Long-term safety experience of ustekinumab in patients with moderate to severe psoriasis (Part II of II): results from analyses of infections and malignancy from pooled phase II and III clinical trials. AB - BACKGROUND: Ustekinumab targets interleukin (IL)-12 and IL-23 in the treatment of moderate to severe psoriasis. OBJECTIVE: We sought to evaluate the impact of ustekinumab on infections and malignancies, both theoretical risks of blocking IL 12 and IL-23, in patients exposed up to 3 years. METHODS: Rates of infections and malignancies were evaluated in cumulative safety data from 3117 ustekinumab treated patients across 4 studies. RESULTS: During the placebo-controlled periods, rates of overall infections per 100 patient-years were similar among placebo (121.0), ustekinumab 45-mg (145.7), and ustekinumab 90-mg (132.2) groups, with overlapping confidence intervals, and remained stable through 3 years in ustekinumab groups. Rates of serious infections during the placebo-controlled periods were similar between placebo (1.70) and 90-mg (1.97) groups, yet lower in the 45-mg group (0.49). Rates remained stable (90 mg) or decreased (45 mg) over time, and were comparable with those for the US psoriasis population based on a managed care database. Rates of malignancies during the placebo-controlled periods were comparable among groups (placebo: 1.70; 45 mg: 0.99; 90 mg: 0.98) and remained stable over time in ustekinumab groups. Rates of malignancies, excluding nonmelanoma skin cancer, were comparable with rates expected in the general US population based on the Surveillance, Epidemiology, and End Results database. LIMITATIONS: Controlled periods do not extend beyond 12 to 20 weeks. Only 1247 patients were treated for at least 2 years, to date. Comparator database populations may not fully represent the clinical trial population. CONCLUSIONS: The emerging safety profile of ustekinumab remains favorable and does not suggest increased rates of infection or malignancy through 3 years. PMID- 21978574 TI - Confocal features of equivocal facial lesions on severely sun-damaged skin: four case studies with dermatoscopic, confocal, and histopathologic correlation. AB - BACKGROUND: Facial skin has a distinct histologic architecture and reveals specific dermatoscopic features. Diagnosis of lentigo maligna on the face is often challenging because of the overlap of clinical and morphologic features with other lesions. OBJECTIVES: We aim to show the value of reflectance confocal microscopy (RCM) as a noninvasive diagnostic tool for facial lesions and to increase knowledge of RCM morphologic features among the scientific community. METHODS: We describe a series of 4 facial lesions on severely sun-damaged skin that was evaluated via RCM immediately after face-to-face examination, followed by shave biopsy for histopathological analysis. RESULTS: Lesions included a lentigo maligna, a pigmented seborrheic keratosis, pigmented basal cell carcinoma, and a pigmented actinic keratosis. In the presented cases, RCM enabled an accurate diagnosis. LIMITATIONS: The study describes morphologic features on selected cases, but does not test accuracy of RCM criteria. CONCLUSIONS: RCM is a useful adjuvant for the accurate and precise diagnosis of equivocal facial lesions. PMID- 21978575 TI - Wet dressing therapy in conjunction with topical corticosteroids is effective for rapid control of severe pediatric atopic dermatitis: experience with 218 patients over 30 years at Mayo Clinic. AB - BACKGROUND: At our institution, hospitalization for intensive treatment (combining wet dressings and topical corticosteroids) is a primary intervention for severe pediatric atopic dermatitis. Prior reports of this treatment are limited. OBJECTIVE: We sought to review the efficacy of wet dressings for pediatric atopic dermatitis. METHODS: We reviewed records of pediatric patients hospitalized from January 1, 1980, through April 20, 2010, who received intensive topical treatments for atopic dermatitis. RESULTS: In total, 218 pediatric patients had widespread atopic dermatitis severe enough to warrant hospitalization, despite prior outpatient topical treatments and other interventions such as immunomodulating agents, phototherapy, dietary manipulation, or contact allergen avoidance. Mean (SD) age was 5.97 (4.91) years (range, 2 months-17 years); 141 patients (65%) were female. There were 266 hospitalizations: 192 patients (72%) had one admission, 15 (6%) had two admissions, and 11 (4%) had 3 or more admissions. Mean (SD) duration of hospitalization was 3.61 (2.23) days (range, 1-16 days). Upon discharge, all patients showed improvement. In 239 of 266 hospitalizations, patient records showed quantification of improvement (global assessment): 121 (45%) had 75% to 100% improvement, 102 (38%) had 50% to 75% improvement, and 16 (6%) had 25% to 50% improvement. LIMITATIONS: This was a retrospective study. CONCLUSION: Intensive inpatient treatment (with wet dressings and topical corticosteroids) was highly effective in controlling severe and recalcitrant atopic dermatitis. Intensive topical treatment, although underused, is an effective first-line approach for patients with severe atopic dermatitis. PMID- 21978576 TI - The development of a rapid SYBR Green I-based quantitative PCR for detection of Duck circovirus. AB - This report describes a one-step real-time polymerase chain reaction assay based on SYBR Green I for detection of a broad range of duck circovirus (DuCV). Align with all DuCV complete genome sequences and other Genus Circovirus download from the GenBank (such as goose circovirus, pigeon circovirus), the primers targets to the replicate gene of DuCV were designed. The detection assay was linear in the range of 1.31 * 102-1.31 * 107 copies/MUL. The reaction efficiency of the assay using the slope (the slope was -3.349) and the Y-intercept was 37.01 from the linear equation was estimated to be 0.99 and the correlation coefficient (R2) was 0.993. A series of experiments were carried out to assess the reproducibility, sensitivity, and specificity of the assay, following by the low intra-assay and inter-assay CVs for CT values obtained with the standard plasmids. The intra assay CVs were equal or less than 1.89% and the inter-assay CVs were equal or less than 1.26%. There was no cross-reaction occurred with nucleic acids extracted from RA (Riemerella anatipestifer), E. coli (Escherichia coli), Duck Cholera (Pasteurella multocida), Avian influenza virus, avian paramyxovirus, Muscovy duck parvovirus, Duck reovirus, Duck hepatitis A virus as control templates. The nucleic acids extracted from samples of healthy ducks were used as negative controls. The assay was specific and reproducible. The established real time PCR was used to detect 45 DuCV-negative samples, which were tested using conventional PCR under the developed optimal conditions, each 15 for embryonated eggs, non-embryonated budgerigar eggs, newly hatched duck, the mixture of the lung, liver, spleen which were analysis for the presence of DuCV DNA, to conform that whether the DuCV can be transmitted vertically. Meanwhile, no positive result was shown by the real-time PCR method. The SYBR Green I-based quantitative PCR can therefore be practically used as an alternative diagnostic tool and a screening method for ducks infected with duck circovirus. PMID- 21978577 TI - Residual structure in unfolded proteins. AB - The denatured state ensemble (DSE) of unfolded proteins, once considered to be well-modeled by an energetically featureless random coil, is now well-known to contain flickering elements of residual structure. The position and nature of DSE residual structure may provide clues toward deciphering the protein folding code. This review focuses on recent advances in our understanding of the nature of DSE collapse under folding conditions, the quantification of the stability of residual structure in the DSE, the determination of the location and types of residues involved in thermodynamically significant residual structure and advances in detection of long-range interactions in the DSE. PMID- 21978578 TI - Differential expression of the TL1A/DcR3 system of TNF/TNFR-like proteins in large vs. small intestinal Crohn's disease. AB - BACKGROUND: TNF-like cytokine 1A provides co-stimulatory signals to activated lymphocytes through binding to death-domain receptor-3. Decoy receptor-3 inhibits death-domain receptor-3 signalling, rendering immunocytes resistant to apoptosis. These functions may be important for the pathogenesis of Crohn's disease. AIMS: To study the mucosal and systemic expression of Decoy receptor-3 and TNF-like cytokine 1A in Crohn's disease, in relation to disease activity, localization, and response to treatment. METHODS: Soluble Decoy receptor-3 and TNF-like cytokine 1A were measured by ELISA in active or quiescent Crohn's disease. Relative mRNA expression in non-affected and inflamed intestinal mucosa was determined by real-time RT-PCR. RESULTS: We found significant upregulation of Decoy receptor-3 and its ligands TNF-like cytokine 1A and FasL in inflamed intestinal mucosa of Crohn's disease patients. During active disease, Decoy receptor-3 and TNF-like cytokine 1A were detected in the serum in the majority of patients. Intestinal inflammation was strongly associated with these elevations as they were absent during remission and significantly reduced with anti inflammatory treatment. Regional diversity was observed as Decoy receptor-3 was upregulated in colonic and ileal sites, whereas TNF-like cytokine 1A was preferentially induced in the large bowel mucosa and systemic circulation of patients with colonic involvement. CONCLUSIONS: TNF-like cytokine 1A and Decoy receptor-3 are upregulated during active Crohn's disease and may participate in disease pathogenesis and offer novel therapeutic opportunities. PMID- 21978579 TI - Comment on: "Intestinal deposits of anti-tissue transglutaminase IgA in childhood celiac disease". PMID- 21978580 TI - Clinical profile and predictors of mortality in patients of acute-on-chronic liver failure. AB - BACKGROUND: Acute-on-chronic liver failure (ACLF) is characterised by acute hepatic insult manifesting as jaundice and coagulopathy, complicated within 4 weeks by ascites and/or encephalopathy in patients with previously diagnosed or undiagnosed chronic liver disease. We studied the clinical, biochemical and etiological profiles of ACLF patients investigating variables which could predict mortality. METHODS: Consecutive ACLF patients were enrolled and given standard intensive care management. They were monitored for predictors of 90-day mortality. RESULTS: 91 patients were included; besides jaundice (median bilirubin 23.1mg/dL) and coagulopathy, acute onset ascites with or without encephalopathy was the presenting symptom in 92%. In all patients a first diagnosis of chronic liver disease was made, mainly due to hepatitis B (37%) or alcohol (34%). Reactivation of chronic hepatitis B and alcoholic hepatitis were the common acute insults. The 90-day mortality was 63%. On multivariate analysis, hepatic encephalopathy, low serum sodium, and high INR were found to be independent baseline predictors of mortality. Amongst all severity scores studied, MELD, SOFA and APACHE-II scores had AUROCs of >0.8 which was significantly higher than that of Child-Turcotte-Pugh. CONCLUSIONS: ACLF has very high mortality. Hepatic encephalopathy, low serum sodium and high INR predict poor outcome. Mortality can also be predicted by baseline MELD, SOFA or APACHE-II scores. PMID- 21978581 TI - Virtual chromoendoscopy: will it play a role in capsule endoscopy? PMID- 21978582 TI - Organo/layered double hydroxide nanohybrids used to remove non ionic pesticides. AB - The preparation and characterization of organo/layered double hydroxide nanohybrids with dodecylsulfate and sebacate as interlayer anion were studied in detail. The aim of the modification of the layered double hydroxides (LDHs) was to change the hydrophilic character of the interlayer to hydrophobic to improve the ability of the nanohybrids to adsorb non-ionic pesticides such as alachlor and metolachlor from water. Adsorption tests were conducted on organo/LDHs using variable pH values, contact times and initial pesticide concentrations (adsorption isotherms) in order to identify the optimum conditions for the intended purpose. Adsorbents and adsorption products were characterized several physicochemical techniques. The adsorption test showed that a noticeable increase of the adsorption of the non-ionic herbicides was produced. Based on the results, the organo/LDHs could be good adsorbents to remove alachlor and metolachlor from water. Different organo/LDHs complexes were prepared by a mechanical mixture and by adsorption. The results show that HTSEB-based complex displays controlled release properties that reduce metolachlor leaching in soil columns compared to a technical product and the other formulations. The release was dependent on the nature of the adsorbent used to prepare the complexes. Thus, it can be concluded that organo/LDHs might act as suitable supports for the design of pesticide slow release formulations with the aim of reducing the adverse effects derived from rapid transport losses of the chemical once applied to soils. PMID- 21978583 TI - Comparison of four bioindication methods for assessing the degree of environmental lead and cadmium pollution. AB - The purpose of this study was to assess the application of several bioindication methods for the monitoring of environmental pollution from Pb and Cd. The study area centered on the town of Olkusz, Poland, which is one of the oldest centers for the metallurgical industry in Europe. The assessment of environmental pollution due to metals was performed using four frequently used bioindication methods: moss-bag (Sphagnum fallax), determination of metal accumulation in Pleurozium schreberi, silver birch foliage, and Scots pine needles. The region of Olkusz, and especially the area surrounding the mining and metallurgical Boleslaw complex, was extremely contaminated with Pb and Cd. The results of the investigations are presented as contamination deposition maps. Despite the application of various methods and the resulting diversity of the specific exposure periods for different biomonitors, the spatial distribution of contamination shown on the maps was similar, as confirmed by the statistical analysis of the results. PMID- 21978584 TI - Nanopaper based on Ag/TiO2 nanobelts heterostructure for continuous-flow photocatalytic treatment of liquid and gas phase pollutants. AB - The Ag/TiO(2) nanobelt heterostructures were prepared by the acid-assisted hydrothermal method followed by an in situ photo-reduction process. The photocatalytic activity of TiO(2) nanobelts was evidently enhanced by the heterostructures between Ag nanoparticles and TiO(2) nanobelts. The nanopapers based on Ag/TiO(2) nanobelt heterostructures were fabricated via a modified paper making process. A novel continuous photocatalytic reactor was designed, and MO removal rate of Ag/C-TiO(2) nanopaper was achieved to 100% in 40 min for single layer and only in 6 min for three layers. The self-supported TiO(2) nanopapers with porous structures also showed an excellent continuous photocatalytic performance for toluene gas under UV light irradiation, and the corresponding degradation rate was 69.5% in 184 min. Moreover, the Ag/TiO(2) nanobelts nanopaper showed a good antibacterial effect. The multifunctional TiO(2) nanopapers modified by the heterostuctures could have potential applications in the environmental and biomaterial fields. PMID- 21978585 TI - Reduction of As(V) to As(III) by commercial ZVI or As(0) with acid-treated ZVI. AB - Zero-valent iron (ZVI) consists of an elemental iron core surrounded by a shell of corrosion products, especially magnetite. ZVI is used for in situ removal or immobilization of a variety of contaminants but the mechanisms for removal of arsenic remain controversial and the mobility of arsenic after reaction with ZVI is uncertain. These issues were addressed by separately studying reactions of As(V) with magnetite, commercial ZVI, and acid-treated ZVI. Strictly anoxic conditions were used. Adsorption of As(V) on magnetite was fast with pH dependence similar to previous reports using oxic conditions. As(V) was not reduced by magnetite and Fe(II) although the reaction is thermodynamically spontaneous. As(V) reactions with ZVI were also fast and no lag phase was observed which was contrary to previous reports. Commercial ZVI reduced As(V) to As(III) only when As(V) was adsorbed, i.e., for pH<7. As(III) was not released to solution. Acid-treated ZVI reduced As(V) to As(0), shown using wet chemical analyses and XANES/EXAFS. Comparisons were drawn between reactivity of acid treated ZVI and nano-ZVI; if true then acid-treated ZVI could provide similar reactive benefits at lower cost. PMID- 21978586 TI - Electrochemical antimony removal from accumulator acid: results from removal trials in laboratory cells. AB - Regeneration of spent accumulator acid could be an alternative process for crystallization, neutralisation and disposal. Therefore, for the first time in a study of the possibilities of electrochemical removal of antimony and accumulator acid regeneration on a laboratory scale, two synthetic and several real systems containing sulfuric acid of concentrations ranging between 28% and 36%, and antimony species were tested. Discontinuous electrochemical reactors with anion exchange membranes were successfully used in these experiments, which were conducted at a temperature of 35 degrees C. Removal of antimony using cells that were not divided by a separator, however, was not possible. In selected experiments, by varying the electrode material, type of electrolyte, and cell current, the concentration of antimony could be reduced from the range of 5 ppm to 0.15 ppm. This resulted in current efficiencies between 0.00002% and 0.001%, and in specific electroenergy demands between 100 Wh L(-1) and 2000 Wh L(-1). In other experiments on substances with antimony contents up to 3500 mg L(-1), the current efficiencies obtained were more than a thousandfold higher. In contrast to the formally high relative energy consumption parameters absolute demand parameters are relatively small and favour the electrochemical method in small scale application. Besides plate electrodes, 3D-cathodes were used. Copper- and graphite cathodes produced the best results. PMID- 21978587 TI - Reconstruction of metal pollution and recent sedimentation processes in Havana Bay (Cuba): a tool for coastal ecosystem management. AB - Since 1998 the highly polluted Havana Bay ecosystem has been the subject of a mitigation program. In order to determine whether pollution-reduction strategies were effective, we have evaluated the historical trends of pollution recorded in sediments of the Bay. A sediment core was dated radiometrically using natural and artificial fallout radionuclides. An irregularity in the (210)Pb record was caused by an episode of accelerated sedimentation. This episode was dated to occur in 1982, a year coincident with the heaviest rains reported in Havana over the XX century. Peaks of mass accumulation rates (MAR) were associated with hurricanes and intensive rains. In the past 60 years, these maxima are related to strong El Nino periods, which are known to increase rainfall in the north Caribbean region. We observed a steady increase of pollution (mainly Pb, Zn, Sn, and Hg) since the beginning of the century to the mid 90 s, with enrichment factors as high as 6. MAR and pollution decreased rapidly after the mid 90 s, although some trace metal levels remain high. This reduction was due to the integrated coastal zone management program introduced in the late 90 s, which dismissed catchment erosion and pollution. PMID- 21978588 TI - Induction of micronuclei by 2-hydroxypyridine in water and elimination of solution genotoxicity by UVC (254 nm) photolysis. AB - 2-Hydroxypyridine (2-HPY) is a major first-stage product formed upon the photolytic destruction of 2-halogenated pyridines. Genotoxicity of 2-HPY in water was studied as a function of concentration. Aqueous solutions of 2-HPY were irradiated by ultraviolet (UV) at 254 nm. 2-HPY concentration, solution total organic carbon (TOC) concentration and solution genotoxicity were measured as a function of treatment time and their profile as a function of time is presented in this work. 2-HPY was found to be genotoxic at all concentrations in the range of 5-400 MUg ml(-1). 2-HPY mineralises completely upon prolonged UV irradiation. All untreated and irradiated solution samples, taken at different photo-treatment times, were tested in cultured human lymphocytes applying the cytokinesis block micronucleus (CBMN) assay. The genotoxicity of the solution was reduced near to the control level after prolonged UV irradiation. PMID- 21978589 TI - Bone morphogenetic protein 15 and growth differentiation factor 9 expression in the ovary of European sea bass (Dicentrarchus labrax): cellular localization, developmental profiles, and response to unilateral ovariectomy. AB - Vertebrate oocytes actively contribute to follicle development by secreting a variety of growth factors, among which bone morphogenetic protein 15 (BMP15/Bmp15) and growth differentiation factor 9 (GDF9/Gdf9) have been paid particular attention. In the present study, we describe the cellular localization, the developmental profiles, and the response to unilateral ovariectomy (a procedure implying the surgical removal of one of the ovaries) of protein and mRNA steady-state levels of Bmp15 and Gdf9 in the ovary of European sea bass, an important fish species for marine aquaculture industry. In situ hybridization and immunohistochemistry demonstrated that the oocyte is the main production site of Bmp15 and Gdf9 in European sea bass ovary. During oocyte development, Bmp15 protein expression started to be detected only from the lipid vesicle stage onwards but not in primary pre-vitellogenic (i.e. perinucleolar) oocytes as the bmp15 mRNA already did. Gdf9 protein and gdf9 mRNA expression were both detected in primary perinucleolar oocytes and followed similar decreasing patterns thereafter. Unilateral ovariectomy induced a full compensatory growth of the remaining ovary in the 2-month period following surgery (A. Garcia-Lopez, M.I. Sanchez-Amaya, C.R. Tyler, F. Prat 2011). The compensatory growth elicited different changes in the expression levels of mRNA and protein of both factors, although the involvement of Bmp15 and Gdf9 in the regulatory network orchestrating such process remains unclear at present. Altogether, our results establish a solid base for further studies focused on elucidating the specific functions of Bmp15 and Gdf9 during primary and secondary oocyte growth in European sea bass. PMID- 21978590 TI - Surgical outcomes in patients with bilateral ptosis and Hering's dependence. AB - PURPOSE: To assess whether sequential or simultaneous ptosis repair yields a better postoperative outcome in patients with documented preoperative Hering's dependency. DESIGN: Retrospective, case-control study. PARTICIPANTS AND CONTROLS: Of the 216 patients who underwent bilateral ptosis surgery, 109 patients with documented Hering's dependency constituted the study group and the 107 patients with no Hering's dependency constituted the control group. METHODS: The charts of patients who underwent levator advancement ptosis surgery between April 2002 and December 2004 by the same surgeon (R.C.K.) were reviewed retrospectively. Data regarding patient demographics, preoperative and postoperative margin-reflex distance values, levator function, presence of Hering's dependency, side of the initial operation, and reoperation status were collected from the charts. Patients demonstrating preoperative Hering's dependency of eyelid position operated simultaneously and sequentially were compared for postoperative symmetry and reoperation rates. Postoperative asymmetry was defined as a more than 1-mm difference between upper eyelid heights. MAIN OUTCOME MEASURES: Postoperative asymmetry and reoperation rates. RESULTS: In the Hering's dependency group (n = 109), 64 sequential surgeries that yielded 15 asymmetric results (23.4%) and 7 reoperations (10.9%) compared with the 45 simultaneous operations, which revealed 1 case of asymmetry (2.2%; P = 0.002) and 1 case of reoperation (2.2%; P = 0.137). Compared with the control group, sequentially operated Hering's dependency patients still showed higher postoperative asymmetry (P = 0.011), and the reoperation rate was similar (P = 0.134). Hering's dependency patients who had the initial operation on the left side demonstrated a significantly higher rate of postoperative asymmetry (42.3% vs. 10.5%; P = 0.006). CONCLUSIONS: Bilateral ptosis cases with documented Hering's dependency yield better results when both eyes are operated in the same session, rather than delaying surgery for the second eyelid. Ocular dominance probably has a significant impact on Hering's dependency and postoperative outcome after unilateral operations. PMID- 21978591 TI - Acquired lower eyelid epiblepharon in thyroid-associated ophthalmopathy of Koreans. AB - PURPOSE: To investigate the prevalence and clinical features of acquired lower eyelid epiblepharon in Korean patients with thyroid-associated ophthalmopathy (TAO) and compare the pathogenic features of acquired and congenital epiblepharon. DESIGN: Retrospective, nonrandomized, comparative case series, cross-sectional study. PARTICIPANTS: A total of 494 Korean patients with TAO and 845 Korean patients with congenital lower eyelid epiblepharon. METHODS: The medical records were reviewed, and the presence, location, and extent of epiblepharon were identified. Clinical features of TAO (lower eyelid retraction, exophthalmos, and elevation limitation) were compared between patients with TAO with and without epiblepharon. Acquired epiblepharon was classified into 3 types according to the location and extent. The prevalence of epiblepharon types was determined and evaluated for associations with TAO clinical features. Comparisons were made between the prevalence of epiblepharon types in acquired and congenital epiblepharon. MAIN OUTCOME MEASURES: Prevalence, location, and extent of epiblepharon; association with clinical features of TAO; and difference from congenital epiblepharon. RESULTS: An acquired lower eyelid epiblepharon was found in 42 (8.5%) of 494 patients with TAO. The mean age of patients with TAO with epiblepharon (34.2+/-13.5 years) was significantly lower than that of patients with TAO without epiblepharon (46.5+/-14.1 years) (P = 0.000). Lower eyelid retraction (0.78+/-1.11 mm) was more severe in patients with TAO with epiblepharon than in patients without epiblepharon (0.30+/-0.73 mm) (P = 0.000). Lower eyelid retraction was more severe in diffuse-type acquired epiblepharon than in central-type epiblepharon (P = 0.012). Elevation limitation was more severe in central-type acquired epiblepharon than in medial-type epiblepharon (P = 0.001). The occurrence of central-type epiblepharon was higher in TAO associated acquired epiblepharon (20 eyelids, 30.8%) than in congenital epiblepharon (27 eyelids, 1.9%, P = 0.000). CONCLUSIONS: Acquired lower eyelid epiblepharon is one of the clinical features of patients with TAO. The association between lower eyelid retraction and acquired epiblepharon may lead to a better understanding of the cause of acquired epiblepharon in patients with TAO. PMID- 21978592 TI - Ultrasound biomicroscopy of anterior segment accommodative changes with posterior chamber phakic intraocular lens in high myopia. AB - PURPOSE: To investigate changes in anterior chamber depth (ACD) and the distance between the Visian implantable Collamer lens (ICL) and the crystalline lens during pharmacologic accommodation in high myopia. DESIGN: Prospective, comparative case series. PARTICIPANTS: Thirty-three phakic eyes of 18 high myopic patients (range, -8.63 to -23.86 diopters) with a mean age of 29 years (range, 20 44 years) were examined at least 1 year after ICL implantation. METHODS: Ultrasound biomicroscopy was used to measure distance changes between the corneal endothelium, the ICL, and the crystalline lens after inducing pharmacologic accommodation with topical pilocarpine in 1 eye. The contralateral eye served as the control. MAIN OUTCOME MEASURES: Mean changes of ACD measured from the posterior corneal surface to the crystalline lens (ACD-L), from the posterior corneal surface to the anterior surface of the ICL (ACD-ICL), and the distance between the ICL and the crystalline lens (ICL-L) at the central and peripheral regions of the eye. RESULTS: For each eye, the ICL was in contact with the iris, but it was never in contact with the crystalline lens. At baseline, the mean distance between the ICL and the crystalline lens was 0.609 +/- 0.165 mm at the central horizontal meridian, 0.588 +/- 0.157 mm at the central vertical meridian, 0.281 +/- 0.106 mm at the peripheral temporal sulcus, and 0.290 +/- 0.098 mm at the peripheral nasal sulcus. After instillation of pilocarpine, a significant decrease in ICL-L was accompanied by a significant reduction in ACD-L and an increase in ACD-ICL (P<0.01). There were no significant changes in the control eyes (P>0.05). The central ICL-L reduction in the study group was significantly larger than that in the control group (P<0.01), but the peripheral ICL-L changes in the study group were not significantly different from those in the controls (P>0.05). CONCLUSIONS: During pharmacologic accommodation, the ICL and the crystalline lens came closer as the ICL was pushed backward by the iris as a result of pupillary constriction. Simultaneously, the anterior surface of the crystalline lens became more convex and moved forward. Reduction of the distances at peripheral sulci was not as obvious as at the center. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. PMID- 21978593 TI - Enhanced depth imaging optical coherence tomography of deep optic nerve complex structures in glaucoma. AB - OBJECTIVE: To assess the usefulness of enhanced depth imaging (EDI) optical coherence tomography (OCT) for evaluating deep structures of the optic nerve complex (ONC; optic nerve head and peripapillary structures) in glaucoma. DESIGN: Prospective, observational study. PARTICIPANTS: Seventy-three established glaucoma patients (139 eyes) with a range of glaucomatous damage. METHODS: Serial horizontal and vertical EDI OCT images of the ONC were obtained from both eyes of each participant. Deep ONC structures, including the lamina cribrosa (LC), short posterior ciliary artery (SPCA), central retinal artery (CRA), central retinal vein (CRV), peripapillary choroid and sclera, and subarachnoid space around the optic nerve, were investigated for their visibility and morphologic features. MAIN OUTCOME MEASURES: Deep ONC structures identified in EDI OCT images. RESULTS: Visual field mean deviation of 139 included eyes was -11.8 +/- 8.6 dB (range, 28.70 to -2.01 dB). The anterior laminar surface was identified in all eyes in the central laminar area and in 91 (65%) eyes in the periphery beneath the neuroretinal and scleral rims or vascular structures. The LC pores with various shapes and sizes were visualized in 106 (76%) eyes, mainly in the central and temporal areas of the LC. Localized LC lesions seen on optic disc photographs were identified as focal LC defects (partial loss of LC tissue) in the EDI OCT images. The locations of the CRA and CRV were identified in all eyes. In the LC, the CRA maintained a straight shape with a consistent caliber, but the CRV (and tributaries) assumed a more irregular shape. The SPCAs, their branches through the emissary canals in the sclera, or both were visualized in 120 (86%) eyes. The subarachnoid space around the optic nerve was identified with varying degrees of clarity in 25 eyes (18%): 17 had high myopia and extensive parapapillary atrophy. Intrachoroidal cavitation or choroidal schisis, which had been unrecognized clinically, was identified in 2 eyes (1%) with high myopia. CONCLUSIONS: Enhanced depth imaging OCT was able to visualize a wide variety of deep ONC structures in glaucoma patients and may be helpful in detecting, conceptualizing, and understanding basic and complicated in vivo anatomic and pathologic features of the ONC in glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. PMID- 21978594 TI - Optic disc change with incipient myopia of childhood. AB - PURPOSE: To describe progressive tilting of the optic nerve head (ONH) and development/enlargement of parapapillary atrophy (PPA) observed in children with incipient myopia and to investigate factors associated with such changes. DESIGN: Retrospective, observational study. PARTICIPANTS: This study included 118 eyes of 118 Korean children who were assessed by serial disc photography at intervals of 1 year or more. METHODS: All disc photographs were reviewed by 2 experienced ophthalmologists, and eyes were classified into 2 groups with respect to the change in the ONH appearance and development/enlargement of beta-zone PPA: (1) ONH/PPA changed group and (2) ONH/PPA unchanged group. To quantify the ONH/PPA changes, the ratio of the horizontal to vertical disc diameter (HVDR) and the ratio of the maximum PPA width to vertical disc diameter (PVDR) were measured. Factors associated with ONH/PPA changes were evaluated using logistic regression analysis. Refractive errors were measured with cycloplegic refraction. MAIN OUTCOME MEASURES: Morphologic changes of the ONH/PPA as observed in serial disc photographs and its association with myopic shift. RESULTS: Mean subject age and refractive error at the time of initial fundus examination were 7.3 +/- 3.7 years (range, 1-17 years) and -0.9 +/- 1.9 diopters (range, -5.9 to +3.0 diopters), respectively. Mean follow-up period was 38.1 +/- 19.6 months (range, 12-88 months). Fifty-one eyes (43%) were classified as the ONH/PPA change group. In the ONH/PPA change group, HVDR decreased from the initial value of 0.92 +/- 0.08 to the final value of 0.86 +/- 0.11, and the PVDR increased from the initial value of 0.08 +/- 0.07 to the final value of 0.20 +/- 0.11. The ONH/PPA changes were most remarkable in subjects between 7 and 9 years of age (odds ratio [OR] = 6.698; 95% confidence interval [CI], 2.296-19.546) and were associated with greater myopic shift during the follow-up period (OR = 0.483; 95% CI, 0.345 0.676). CONCLUSIONS: We demonstrate progressive tilting of the ONH, which was observed with development/enlargement of PPA in children who exhibited myopic shift. These findings suggest that tilted disc, as well as PPA, may be an acquired feature in myopic eyes, arising from scleral stretching. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. PMID- 21978596 TI - Direct in vivo interaction of the antibiotic primycin with the plasma membrane of Candida albicans: an EPR study. AB - The direct interaction of the antibiotic primycin with the plasma membrane was investigated by employing the well-characterized ergosterol-producing, amphotericin B-sensitive parental Candida albicans strain 33erg(+) and its ergosterol-less amphotericin B-resistant plasma membrane mutant erg-2. The growth inhibition concentration in shaken liquid medium was 64 MUgml(-1) for 33erg(+) and 128 MUgml(-1) for erg-2, suggesting that the plasma membrane composition influences the mode of action of primycin. To determine the primycin-induced changes in the plasma membrane dynamic, electron paramagnetic resonance (EPR) spectroscopy methods were used, the spin-labeled fatty acid 5-(4,4 dimethyloxazolidine-N-oxyl)stearic acid) being applied for the in vivo measurements. The phase transition temperatures of untreated strain 33erg(+) and its mutant erg-2 were 12.5 degrees C and 11 degrees C, respectively. After 128 MUgml(-1) primycin treatment, these values increased to 17.5 degrees C and 16 degrees C, revealing a significant reduction in the phospholipid flexibility. Saturation transfer EPR measurements demonstrated that, the rotational correlation times of the spin label molecule for the control samples of 33erg(+) and erg-2 were 60 ns and 100 ns. These correlation times gradually decreased on the addition of increasing primycin concentrations, reaching 8 MUs and 1 MUs. The results indicate the plasma membrane "rigidizing" effect of primycin, a feature that may stem from its ability to undergo complex formation with membrane constituent fatty acid molecules, causing alterations in the structures of phospholipids in the hydrophobic surface near the fatty acid chain region. PMID- 21978595 TI - Voltage-dependent conformational changes in connexin channels. AB - Channels formed by connexins display two distinct types of voltage-dependent gating, termed V(j)- or fast-gating and loop- or slow-gating. Recent studies, using metal bridge formation and chemical cross-linking have identified a region within the channel pore that contributes to the formation of the loop-gate permeability barrier. The conformational changes are remarkably large, reducing the channel pore diameter from 15 to 20A to less than 4A. Surprisingly, the largest conformational change occurs in the most stable region of the channel pore, the 3(10) or parahelix formed by amino acids in the 42-51 segment. The data provide a set of positional constraints that can be used to model the structure of the loop-gate closed state. Less is known about the conformation of the V(j) gate closed state. There appear to be two different mechanisms; one in which conformational changes in channel structure are linked to a voltage sensor contained in the N-terminus of Cx26 and Cx32 and a second in which the C-terminus of Cx43 and Cx40 may act either as a gating particle to block the channel pore or alternatively to stabilize the closed state. The later mechanism utilizes the same domains as implicated in effecting pH gating of Cx43 channels. It is unclear if the two V(j)-gating mechanisms are related or if they represent different gating mechanisms that operate separately in different subsets of connexin channels. A model of the V(j)-closed state of Cx26 hemichannel that is based on the X-ray structure of Cx26 and electron crystallographic structures of a Cx26 mutation suggests that the permeability barrier for V(j)-gating is formed exclusively by the N-terminus, but recent information suggests that this conformation may not represent a voltage-closed state. Closed state models are considered from a thermodynamic perspective based on information from the 3.5A Cx26 crystal structure and molecular dynamics (MD) simulations. The applications of computational and experimental methods to define the path of allosteric molecular transitions that link the open and closed states are discussed. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics. PMID- 21978597 TI - A gate-free pathway for substrate release from the inward-facing state of the Na+ galactose transporter. AB - Employing molecular dynamics (MD) simulations, the pathway and mechanism of substrate unbinding from the inward-facing state of the Na(+)-coupled galactose transporter, vSGLT, have been investigated. During a 200-ns equilibrium simulation, repeated spontaneous unbinding events of the substrate from its binding site have been observed. In contrast to the previously proposed gating role of a tyrosine residue (Y263), the unbinding mechanism captured in the present equilibrium simulation does not rely on the displacement and/or rotation of this side chain. Rather, the unbinding involves an initial lateral displacement of the substrate out of the binding site which allows the substrate to completely emerge from the region covered by the side chain of Y263 without any noticeable conformational changes of the latter. Starting with the snapshots taken from this equilibrium simulation with the substrate outside the binding site, steered MD (SMD) simulations were then used to probe the translocation of the substrate along the remaining of the release pathway within the protein's lumen and to characterize the nature of protein-substrate interactions involved in the process. Combining the results of the equilibrium and SMD simulations, we provide a description of the full translocation pathway for the substrate release from the binding site into the cytoplasm. Residues E68, N142, T431, and N267 facilitate the initial substrate's displacement out of the binding site, while the translocation of the substrate along the remainder of the exit pathway formed between TM6 and TM8 is facilitated by H-bond interactions between the substrate and a series of conserved, polar residues (Y138, N267, R273, S365, S368, N371, S372, and T375). The observed molecular events indicate that no gating is required for the release of the substrate from the crystallographically captured structure of the inward-facing state of SGLT, suggesting that this conformation might represent an open, rather than occluded, state of the transporter. This article is part of a Special Issue entitled: Membrane protein structure and function. PMID- 21978598 TI - Pharmacokinetics of the low molecular weight heparin dalteparin in cats. AB - Low molecular weight heparin (LMWH) is used as an anticoagulant in cats although only limited pharmacokinetic data are available in this species. The aim of the present study was to establish the pharmacokinetics of dalteparin in cats based on anti-FXa heparin activities. Groups of clinically healthy cats (six animals per treatment) received individual LMWH injections at three different doses intravenously (IV) (25, 50, 100 anti-factor Xa international units [IU anti FXa]/kg) or subcutaneously (SC) (50, 100, 200 IU anti-FXa/kg). Blood samples were collected before and at various times after injection. Anti-FXa activity was measured with a chromogenic substrate test. Following IV injection, maximum plasma heparin activities (C(max)) were 0.67 +/- 0.14, 1.44 +/- 0.22 and 2.87 +/- 0.38 IU anti-FXa/mL, respectively. The calculated mean half-life (t(1/2)) was between 39 and 57 min and was not significantly dose-dependent (P=0.139). The volume of distribution (35-39 mL/kg) was almost equivalent to the plasma volume. After SC injection, C(max) values of 0.41 +/- 0.10, 0.86 +/- 0.17 or 1.91 +/- 0.16 IU anti-FXa/mL, respectively, were calculated at 91-110 min post-injection. The t(1/2) values were between 106 and 122 min and were not significantly influenced by dose (P=0.784). The bioavailability after SC injection was approximately 100%. The high bioavailability of the SC administered LMWH dalteparin in cats was consistent with other species and indicated predictable blood levels. However, the comparatively short t(1/2) may indicate the necessity of multiple daily injections, which should be verified in clinical trials. PMID- 21978600 TI - Endoplasmic reticulum stress in UMOD-related kidney disease: a human pathologic study. AB - Mutations of the UMOD gene, which encodes the uromodulin protein, are associated with tubulointerstitial nephritis and hyperuricemia. UMOD mutations impair uromodulin folding, resulting in its retention within the endoplasmic reticulum (ER) of renal tubular cells. The aim of this study was to investigate whether mutant uromodulin accumulation in epithelial tubular cells is associated with ER stress. We characterized tubular expression of uromodulin and the ER stress surrogate marker Grp78 by immunohistochemistry in kidney biopsy specimens from 7 patients with UMOD-related kidney disease. We compared this population with 5 patients with familial tubulointerstitial nephritis not related to UMOD mutation. All biopsy specimens from patients carrying the UMOD mutation showed strong heterogeneous cytoplasmic expression of uromodulin in cells of the thick ascending limb of the loop of Henle. In the same tubules, Grp78 was highly expressed in a perinuclear pattern. In contrast, in all kidney biopsy specimens from patients without UMOD mutations, uromodulin staining showed normal apical expression and Grp78 expression was not increased. Our observations support the hypothesis that ER accumulation of mutant uromodulin may cause ER stress, providing a potential mechanism for the progression of UMOD-related kidney disease. PMID- 21978599 TI - Economic instruments for obesity prevention: results of a scoping review and modified Delphi survey. AB - BACKGROUND: Comprehensive, multi-level approaches are required to address obesity. One important target for intervention is the economic domain. The purpose of this study was to synthesize existing evidence regarding the impact of economic policies targeting obesity and its causal behaviours (diet, physical activity), and to make specific recommendations for the Canadian context. METHODS: Arksey and O'Malley's (2005) methodological framework for conducting scoping reviews was adopted for this study and this consisted of two phases: 1) a structured literature search and review, and 2) consultation with experts in the research field through a Delphi survey and an in-person expert panel meeting in April 2010. RESULTS: Two key findings from the scoping review included 1) consistent evidence that weight outcomes are responsive to food and beverage prices. The debate on the use of food taxes and subsidies to address obesity should now shift to how best to address practical issues in designing such policies; and 2) very few studies have examined the impact of economic instruments to promote physical activity and clear policy recommendations cannot be made at this time. Delphi survey findings emphasised the relatively modest impact any specific economic instrument would have on obesity independently. Based on empirical evidence and expert opinion, three recommendations were supported. First, to create and implement an effective health filter to review new and current agricultural polices to reduce the possibility that such policies have a deleterious impact on population rates of obesity. Second, to implement a caloric sweetened beverage tax. Third, to examine how to implement fruit and vegetable subsidies targeted at children and low income households. CONCLUSIONS: In terms of economic interventions, shifting from empirical evidence to policy recommendation remains challenging. Overall, the evidence is not sufficiently strong to provide clear policy direction. Additionally, the nature of the experiments needed to provide definitive evidence supporting certain policy directions is likely to be complex and potentially unfeasible. However, these are not reasons to take no action. It is likely that policies need to be implemented in the face of an incomplete evidence base. PMID- 21978601 TI - Cognitive development in very vs. moderately to late preterm and full-term children: can effortful control account for group differences in toddlerhood? AB - BACKGROUND: Preterm birth is thought to have an adverse impact on cognitive development and self-regulation. AIM: Examining the effect of very vs. moderately to late premature birth on cognitive development and effortful control, as well as evaluating whether effortful control explains the link between preterm birth and poorer cognitive development. SUBJECTS: Fifty-eight very preterm children (<32 weeks gestation or <1500 g birth weight), 88 moderately to late preterm children (>=32 weeks gestation and >=1500 birth weight) and 86 full-term children (>=38 weeks gestation and >=2500 g birth weight) were examined at the corrected age of 24 months. OUTCOME MEASURES: Observational and parent-report measures of effortful control as well as the Bayley Scales of Infant Development II (BSID II, Mental Scale) as a measurement of cognitive development were analyzed. RESULTS: Very preterm and moderately to late preterm children showed significantly lower cognitive performance compared to full-term children. Lower effortful control scores (on observational measures, but not on parent-reports) were merely found for very preterm children compared to full-term children. Observational measures of effortful control partially mediated the effects of very preterm birth on cognitive performance, but did not explain the effects of moderately to late preterm birth on cognitive performance. CONCLUSION: Preterm birth in general is related to poorer cognitive performance in toddlerhood. In addition, effortful control mediates the effects of very preterm birth on cognitive development. Findings suggest that different mechanisms link moderately to late premature birth to poor cognitive development. PMID- 21978602 TI - Mothers, babies and vitamin D: old disease, new problem. AB - Neonatologists and paediatricians have a crucial role working with mothers at the most nutritionally challenged point in their lives and that of their infants. This position of responsibility is particularly important in tackling the re emerging problem of hypovitaminosis D. In this overview the role of vitamin D, its contribution to pathology in those to whom we provide a service and possible actions will be considered. PMID- 21978604 TI - Expression and purification of soluble bio-active rice plant catalase-A from recombinant Escherichia coli. AB - Catalase in plants is a heme-coordinated tetrameric protein that primarily disproportionates hydrogen peroxide into water and oxygen. It plays an important role in maintaining cellular concentration of hydrogen peroxide to a level, necessary for all aspects of normal plant growth and development. Except for its recombinant expression in transgenic plants and insect cell line, the protein is yet to be synthesized in its bio-active form in prokaryotic expression system. Attempts made in past for recombinant expression of plant catalase in Escherichia coli consistently resulted in formation of insoluble and inactive aggregates of inclusion body. Here we have shown the specific requirement of a thioredoxin fusion partner, the involvement of trigger factor protein and the low temperature treatment during induction period for synthesis of completely solubilized rice plant catalase-A in recombinant E. coli. Furthermore, the bacteria required the supplementation of delta-aminolevulinic acid to produce bio-active recombinant rice catalase-A. The molecular and biochemical properties of the purified recombinant protein showed the characteristic features of a typical mono functional plant catalase. These results attest to the usefulness of the present protocol for production of plant catalase using E. coli as heterologous expression system. PMID- 21978603 TI - Human brain atlas-based multimodal MRI analysis of volumetry, diffusimetry, relaxometry and lesion distribution in multiple sclerosis patients and healthy adult controls: implications for understanding the pathogenesis of multiple sclerosis and consolidation of quantitative MRI results in MS. AB - Multiple sclerosis (MS) is the most common immune-mediated disabling neurological disease of the central nervous system. The pathogenesis of MS is not fully understood. Histopathology implicates both demyelination and axonal degeneration as the major contributors to the accumulation of disability. The application of several in vivo quantitative magnetic resonance imaging (MRI) methods to both lesioned and normal-appearing brain tissue has not yet provided a solid conclusive support of the hypothesis that MS might be a diffuse disease. In this work, we adopted FreeSurfer to provide standardized macrostructure or volumetry of lesion free normal-appearing brain tissue in combination with multiple quantitative MRI metrics (T(2) relaxation time, diffusion tensor anisotropy and diffusivities) that characterize tissue microstructural integrity. By incorporating a large number of healthy controls, we have attempted to separate the natural age-related change from the disease-induced effects. Our work shows elevation in diffusivity and relaxation times and reduction in volume in a number of normal-appearing white matter and gray matter structures in relapsing remitting multiple sclerosis patients. These changes were related in part with the spatial distribution of lesions. The whole brain lesion load and age-adjusted expanded disability status score showed strongest correlations in regions such as corpus callosum with qMRI metrics that are believed to be specific markers of axonal dysfunction, consistent with histologic data of others indicating axonal loss that is independent of focal lesions. Our results support that MS at least in part has a neurodegenerative component. PMID- 21978605 TI - In-hospital resuscitation evaluated by in situ simulation: a prospective simulation study. AB - BACKGROUND: Interruption in chest compressions during cardiopulmonary resuscitation can be characterized as no flow ratio (NFR) and the importance of minimizing these pauses in chest compression has been highlighted recently. Further, documentation of resuscitation performance has been reported to be insufficient and there is a lack of identification of important issues where future efforts might be beneficial. By implementing in situ simulation we created a model to evaluate resuscitation performance. The aims of the study were to evaluate the feasibility of the applied method, and to examine differences in the resuscitation performance between the first responders and the cardiac arrest team. METHODS: A prospective observational study of 16 unannounced simulated cardiopulmonary arrest scenarios was conducted. The participants of the study involved all health care personel on duty who responded to a cardiac arrest. We measured NFR and time to detection of initial rhythm on defibrillator and performed a comparison between the first responders and the cardiac arrest team. RESULTS: Data from 13 out of 16 simulations was used to evaluate the ability of generating resuscitation performance data in simulated cardiac arrest. The defibrillator arrived after median 214 seconds (180-254) and detected initial rhythm after median 311 seconds (283-349). A significant difference in no flow ratio (NFR) was observed between the first responders, median NFR 38% (32-46), and the resuscitation teams, median NFR 25% (19-29), p < 0.001. The difference was significant even after adjusting for pulse and rhythm check and shock delivery. CONCLUSION: The main finding of this study was a significant difference between the first responders and the cardiac arrest team with the latter performing more adequate cardiopulmonary resuscitation with regards to NFR. Future research should focus on the educational potential for in-situ simulation in terms of improving skills of hospital staff and patient outcome. PMID- 21978606 TI - Effectiveness of seasonal influenza vaccination in healthcare workers: a systematic review. AB - Vaccination is considered a key measure to protect vulnerable groups against influenza infection. The objectives of this review are to determine the effect of influenza vaccinations in reducing laboratory-confirmed influenza infections, influenza-like illnesses (ILIs), working days lost among vaccinated HCWs, and associated adverse effects after vaccination. Twenty-two healthcare-related databases and internet resources, as well as reference lists, and the bibliographies of all of the retrieved articles were examined. All randomized controlled trials (RCTs) comparing the effectiveness of any kind of influenza vaccine among all groups of HCWs with a placebo/vaccine other than the influenza vaccine/no intervention were included in the review. Only three RCTs matched the inclusion criteria. There is a limited amount of evidence suggesting that receiving influenza vaccination reduces laboratory-confirmed influenza infections in HCWs. No evidence can be found of influenza vaccinations significantly reducing the incidence of influenza, number of ILI episodes, days with ILI symptoms, or amount of sick leave taken among vaccinated HCWs. There is insufficient data to assess the adverse effects after vaccination. There is no definitive conclusion on the effectiveness of influenza vaccinations in HCWs because of the limited number of related trials. Further research is necessary to evaluate whether annual vaccination is a key measure to protect HCWs against influenza infection and thus increase their confidence in the vaccine. In the mean time, the direction of promoting influenza vaccination to HCWs can be shifted from staff protection to patient protection, with accurate information to address concerns and misconceptions. PMID- 21978607 TI - Hand hygiene: are we trying to make the patient the fail-safe system? PMID- 21978608 TI - Tuberculosis infection control in rural South Africa: survey of knowledge, attitude and practice in hospital staff. AB - A baseline assessment of tuberculosis infection control (TB IC) knowledge, attitude and practice (KAP) was conducted among staff in a resource-limited rural South African hospital where nosocomially transmitted multi- and extensively drug resistant (M/XDR) TB had been reported. Assessment consisted of anonymous questionnaires and direct observation during July-September 2007, soon after the report of M/XDR-TB. Data were obtained from 57 questionnaires and 10h of direct observation. While knowledge and attitudes were generally supportive of TB IC implementation, 49.1% of staff felt that the hospital did not care about them and/or was not working to prevent staff TB infections, and 42.9% were less willing to continue as a healthcare worker because of staff TB/MDR-TB/XDR-TB deaths. Practices were variable. The recent appointment of an IC officer and implementation of natural ventilation were strengths, but the facility lacked a TB IC policy, the patient TB screening process was inadequate, and 41.5% of respondents were unaware of their personal human immunodeficiency virus (HIV) status. Respondents reported a number of barriers to TB IC implementation such as concerns about the confidentiality of staff health information, the stigma of TB and HIV, inadequate resources, and patient non-compliance. Assessment of staff KAP provided useful data regarding deficits and barriers to TB IC, and helped to focus subsequent IC strategies. Given the critical importance of reducing nosocomial TB transmission, it is recommended that facilities should conduct simplified TB IC assessment, ensure the confidentiality of staff health information, address the stigma of TB/HIV, and implement multi-faceted TB IC facility and behavioural change interventions. Behavioural science methods have the potential to improve TB IC research and implementation. PMID- 21978609 TI - MRSA surveillance in a UK district hospital: measuring clinical isolates with MRSA is more useful than measuring MRSA bacteraemias. AB - The introduction of mandatory surveillance of meticillin-resistant Staphylococcus aureus (MRSA) bacteraemias and targets in England has led to reductions in most hospitals. However, reductions were difficult to demonstrate at Peterborough & Stamford Hospitals NHS Foundation Trust as MRSA bacteraemia was already an uncommon event. The authors questioned the efficacy of monitoring bacteraemias in a low-prevalence hospital, and this study sought to determine the accuracy of measuring bacteraemias compared with all clinical isolates (excluding bacteraemias; e.g. wound, sputa, urine) to assess the effectiveness of interventions. Over the six-year study period, a significant reduction was seen in MRSA in clinical specimens and new MRSA carriers identified by screening, whereas the MRSA bacteraemia rate remained at low levels. The measurement of clinical isolates may be more useful for assessment of the effectiveness of interventions now that MRSA bacteraemia rates have fallen to low levels almost universally across the UK. PMID- 21978610 TI - Early biomechanical keratoconus pattern measured with an ocular response analyzer: curve analysis. AB - PURPOSE: To estimate the ability of the Ocular Response Analyzer parameters to aid in the diagnosis of keratoconus in pre-laser in situ keratomileusis (LASIK) patients. SETTING: Department of Ophthalmology, Bordeaux 2 University, Bordeaux Cedex, France. DESIGN: Evaluation of diagnostic test. METHODS: This study compared eyes with mild stages of keratoconus (study group) with preoperative eyes that later had LASIK (control group). Corneas with a central thickness within 500 to 600 MUm were targeted. The biomechanical measurements were acquired, and 12 parameters were analyzed after extraction from the signal data. RESULTS: The study group comprised 103 eyes and the control group, 97 eyes. The mean corneal hysteresis (CH) was 9.2 mm Hg in study eyes and 10.1 mm Hg in control eyes and the mean corneal resistance factor (CRF), 8.9 mm Hg and 10.6 mm Hg, respectively. For a threshold of 9.6, CH had a sensitivity of 66% with a specificity of 67%. For a threshold of 9.7, the CRF had a sensitivity of 72% and a specificity of 77%. For 6 biomechanical parameters, the probability that a patient would present with keratoconus was 3 in 1000 if 1 parameter was over the chosen threshold. CONCLUSIONS: If 1 of 6 parameters were over a chosen threshold, the probability that a patient would present with keratoconus would be almost 3 in 1000 instead of 9 in 1000 in a LASIK surgery cohort. Despite low sensitivity and specificity, some parameters provided by the corneal analyzer offered high negative likelihood ratios and deserve more study with bigger samples. PMID- 21978611 TI - Structure of the O-polysaccharide from the lipopolysaccharide of Providencia alcalifaciens O28. AB - An O-polysaccharide and oligosaccharides were isolated by GPC following mild acid degradation of the lipopolysaccharide of Providencia alcalifaciens O28. The O polysaccharide was studied by sugar and methylation analyses, (1)H and (13)C NMR spectroscopy, including 2D ROESY and H-detected (1)H,(13)C HSQC and HMBC experiments, and the following structure of the branched pentasaccharide repeating unit was established: [see formula in text]. This structure was confirmed by ESI MS of the isolated tridecasaccharide consisting of the lipopolysaccharide core and one O-polysaccharide repeat. The ESI mass spectrum also enabled inferring the composition of the core oligosaccharide. PMID- 21978612 TI - The novel use of a routine quantitative system to analyze the activity, content and affinity of an antibody to hepatitis B core antigen. AB - BACKGROUND: Currently, quantitative measurement of serum markers of HBV infection has been widely used, but commonly used analysis for specific antibodies only involves the measurement of the total antibody activity, and the binding affinity or protein content is rarely analyzed. OBJECTIVE: To investigate the detailed features of an antibody to hepatitis B core antigen (anti-HBc) during different periods of hepatitis B virus (HBV) infection with a new method of analysis. STUDY DESIGN: Serum samples were collected from patients that were positive for the anti-HBc antibody. On the basis of the other serological markers in the samples, all patients were divided into a hepatitis B surface antigen (HBsAg)-positive group and an antibody to hepatitis B surface antigen (anti-HBs)-positive group. All samples were diluted 2-, 20- and 200-fold. Anti-HBc quantification was measured with a chemiluminescent microparticle immunoassay; total anti-HBc activity, protein content and affinity were calculated according to a measured value of each dilution. Serum HBV DNA load and alanine aminotransferase (ALT) levels were also measured. RESULTS: The total anti-HBc activity in the HBsAg positive group was statistically higher than that in the anti-HBs-positive group (p<0.05). The anti-HBc protein content during active HBV infection was statistically higher than during the convalescence stage (p<0.05), while anti-HBc affinity during HBV infection was lower than during recovery. There were correlations among total activity, affinity, protein content of anti-HBc, and ALT, HBV-DNA (p<0.05). CONCLUSIONS: It is potentially possible to predict the status of HBV infection by measuring total activity, protein content and affinity of anti-HBc. PMID- 21978613 TI - Human coronavirus NL-63 infection in a Brazilian patient suspected of H1N1 2009 influenza infection: description of a fatal case. AB - Human coronaviruses (HCoVs) cause upper respiratory tract and occasionally lower respiratory tract diseases. The recently described human coronavirus NL63 has not been well investigated among Brazilian patients. We reported the clinical course of an HCoV-NL63 infection in a hospitalised patient suspected of H1N1 2009 infection during the second pandemic wave of influenza activity. A 46-year-old female, health care worker with diabetes and presenting with influenza-like illness (ILI) was admitted to the hospital. During 9 days of influenza-like symptoms, the patient had diabetes decompensation, haemorrhagic pneumonia, rhabdomyolysis, respiratory and renal failure, pericarditis, and brain edema and died. HCoV-NL63 may be a causative agent of previously unexplained respiratory illnesses. PMID- 21978614 TI - Automatic on-line monitoring of atmospheric volatile organic compounds: gas chromatography-mass spectrometry and gas chromatography-flame ionization detection as complementary systems. AB - Traditionally air quality networks have been carrying out the continuous, on-line measurement of volatile organic compounds (VOC) in ambient air with GC-FID. In this paper some identification and coelution problems observed while using this technique in long-term measurement campaigns are described. In order to solve these problems a GC-MS was set up and operated simultaneously with a GC-FID for C2-C11 VOCs measurement. There are few on-line, unattended, long term measurements of atmospheric VOCs performed with GC-MS. In this work such a system has been optimized for that purpose, achieving good repeatability, linearity, and detection limits of the order of the GC-FID ones, even smaller in some cases. VOC quantification has been made by using response factors, which is not frequent in on-line GC-MS. That way, the identification and coelution problems detected in the GC-FID, which may led to reporting erroneous data, could be corrected. The combination of GC-FID and GC-MS as complementary techniques for the measurement of speciated VOCs in ambient air at sub-ppbv levels is proposed. Some results of the measurements are presented, including concentration values for some compounds not found until now on public ambient air VOC databases, which were identified and quantified combining both techniques. Results may also help to correct previously published VOC data with wrongly identified compounds by reprocessing raw chromatographic data. PMID- 21978615 TI - An event-related analysis of awakening reactions due to nocturnal church bell noise. AB - The sleep disturbing effects of nocturnal ambient non-traffic related noises such as bell strokes emitted from church bell towers on nearby residents are presently unknown. Nonetheless, this specific noise source is suspected to cause sleep disturbances in a small but qualified minority of people living in the vicinity of the bell towers that throughout the night indicate the time with bell ringings. A field study was carried out to elucidate whether acoustic properties of such bell strokes relate to awakening and to provide event-related exposure effect functions between acoustical predictors and awakening probability. Awakening reactions were determined in 27 voluntary subjects, measured in their home setting for four consecutive nights with ambulatory polysomnography (PSG) and concurrent acoustic recordings in- and outside the dwelling. Results indicate that the bell ringing events increase awakenings in a similar fashion as has previously been reported with transportation noise events and that awakening probability first and foremost depends on maximum sound pressure level of an event. The number of bell strokes and the personal variables gender, age, and noise sensitivity did not influence awakening probability significantly. Awakening probability by tendency increased with elapsed time after sleep onset, and was decreased during slow wave sleep and REM sleep compared to S2 sleep. The results suggest that a reduction of the maximum sound pressure level or an interruption of ringings during nighttime might reduce awakenings. The determined exposure-effect relationships are compared with similar functions for impulsive noise and transportation noise, more specifically, aircraft noise. The paper concludes with a few considerations regarding nighttime noise regulation. PMID- 21978616 TI - Boron exposure assessment using drinking water and urine in the North of Chile. AB - Boron is an essential trace element for plants and humans however it is still an open question what levels of boron are actually safe for humans. This study, conducted between 2006 and 2010, measured exposure levels of boron in drinking water and urine of volunteers in Arica, an area in the North of Chile with high levels of naturally occurring boron. Samples were taken of tap and bottled water (173 and 22, respectively), as well as urine from 22 volunteers, and subsequently analyzed by inductively coupled plasma spectroscopy (ICP-OES). Boron varied in public tap water from 0.22 to 11.3mgL(-1), with a median value of 2.9mgL(-1), while concentrations of boron in bottled water varied from 0.01 to 12.2mgL(-1). Neither tap nor bottled water samples had concentrations of boron within WHO recommended limits. The concentration of boron in urine varied between 0.45 and 17.4mgL(-1), with a median of 4.28mgL(-1) and was found to be correlated with tap water sampled from the homes of the volunteers (r=0.64). Authors highly recommend that in northern Chile - where levels of boron are naturally high - that the tap and bottled water supplies be monitored in order to protect public health and that regulatory standards also be established for boron in drinking water in order to limit exposure. PMID- 21978617 TI - Effects of airflow on odorants' emissions in a model pig house - A laboratory study using Proton-Transfer-Reaction Mass Spectrometry (PTR-MS). AB - Identification of different factors that affect emissions of gasses, including volatile organic compounds (VOCs) is necessary to develop emission abatement technology. The objectives of this research were to quantify and study temporal variation of gas emissions from a model pig house under varying ventilation rates. The used model was a 1:12.5 scale of a section of a commercial finishing pig house. The VOC concentrations at inlet, outlet, and slurry pit of the model space were measured using Proton-Transfer-Reaction Mass Spectrometry (PTR-MS). PTR-MS can measure the temporal variations of odor compounds' emission from the slurry pit in real time. The emissions of H(2)S and 14 VOCs were lower compared to real pig buildings except for ammonia, which indicated possible other sources of those compounds than the slurry in the slurry pit. The ventilation rate affected significantly on ammonia and trimethylamine emission (p<0.05). The hydrogen sulfide (H(2)S) emission was independent of the ventilation rate. VFAs' emission dependency on ventilation rate increased with the increase of carbon chain. Phenols, indoles and ketones showed the positive correlation with ventilation rate to some extent. Generally, compounds with high solubility (low Henry's constant) showed stronger correlation with ventilation rates than the compounds with high Henry's constant. PMID- 21978618 TI - Acute mortality effects of carbon monoxide in the Pearl River Delta of China. AB - OBJECTIVES: Several studies reported acute mortality and morbidity effects of exposure to carbon monoxide (CO); which, however, has been least studied in Chinese population at regional scale. METHODS: We conducted a time-series analysis assessing mortality effects of CO in four cities located in the Pearl River Delta (PRD) of China, a labor and resource intensive city cluster, using daily mortality and air pollution data (2006-2008). Generalized linear model with Poisson regression incorporating natural spline functions was used to analyze the effects of exposure to ambient CO on total (nonaccidental), cardiovascular and respiratory mortality. Effect estimates were determined first for individual cities, and then focused for the mega-city Guangzhou. RESULTS: We found exposure to CO was significantly associated with increased mortality in the mega-city of Guangzhou and medium-sized industrial city of Foshan. In specific, per 0.5ppm increase in the average lag 1-2 (previous two days) exposure to CO was associated with 3.04% [95% confidence interval (CI), 2.18-3.90%], 3.62% (95% CI, 2.20-5.06%) and 3.72% (95% CI, 1.71-5.76%) increases in excessive risks (ERs) of total, cardiovascular and respiratory mortality, in Guangzhou. Further, we observed significant heterogeneity in mortality effects of exposure to CO among the four PRD cities of different development levels: stronger mortality effects were found in larger, more developed and industrialized cities. CONCLUSIONS: Exposure to ambient CO is associated with significant increases in total, cardiovascular and respiratory mortality in Chinese population. CO is an established biologic toxicant, whereas the effects and possible mechanisms of exposure to ambient level of CO and co-pollutants warrant further investigation. PMID- 21978619 TI - Bioaccumulation of persistent organic pollutants (POPs) in fish species from Lake Koka, Ethiopia: The influence of lipid content and trophic position. AB - The concentrations and bioaccumulation of persistent organic pollutants (POPs) were determined in four fish species from Lake Koka, Ethiopia, representing 2-3 levels in the food chain of the lake. Dichlorodiphenyltrichloroethanes (DDTs), endosulfans, polychlorinated biphenyls (PCBs) and chlorpyrifos were identified, with DDTs as the most predominant pesticide, with concentration ranging from 0.05 to 72.53ngg(-1) wet weight (ww). All fish tissue samples collected from different species of the lake contained residues of DDTs. The maximum level of DDTs was found in the fattiest, African sharptooth catfish (Clarias gariepinus) sampled from the lake, with a mean concentration of 15.15ngg(-1)ww. The significant (P<0.05) relationship between concentrations of DDTs and delta(15)N indicates that DDTs biomagnified in the food web of the lake. The 4,4'-DDE to 4,4'-DDT ratio in Oreochromis niloticus (0.6) and Cyprinus carpio (0.5) were below 1, indicating ongoing use of DDTs in the study area and recent exposure of these fish species. PMID- 21978620 TI - Complex pleural empyema can be safely treated with vacuum-assisted closure. AB - OBJECTIVE: For patients with postoperative pleural empyema, open window thoracostomy (OWT) is often necessary to prevent sepsis. Vacuum-assisted closure (VAC) is a well-known therapeutic option in wound treatment. The efficacy and safety of intrathoracal VAC therapy, especially in patients with pleural empyema with bronchial stump insufficiency or remain lung, has not yet been investigated. METHODS: Between October 2009 and July 2010, eight consecutive patients (mean age of 66.1 years) with multimorbidity received an OWT with VAC for the treatment of postoperative or recurrent pleural empyema. Two of them had a bronchial stump insufficiency (BPF). RESULTS: VAC therapy ensured local control of the empyema and control of sepsis. The continuous suction up to 125 mm Hg cleaned the wound and thoracic cavity and supported the rapid healing. Additionally, installation of a stable vacuum was possible in the two patients with BPF. The smaller bronchus stump fistula closed spontaneously due to the VAC therapy, but the larger remained open. The direct contact of the VAC sponge did not create any air leak or bleeding from the lung or the mediastinal structures. The VAC therapy allowed a better re-expansion of remaining lung. One patient died in the late postoperative period (day 47 p.o.) of multiorgan failure. In three cases, VAC therapy was continued in an outpatient service, and in four patients, the OWT was treated with conventional wound care. After a mean time of three months, the chest wall was closed in five of seven cases. However, two patients rejected the closure of the OWT. After a follow-up at 7.7 months, neither recurrent pleural empyema nor BPF was observed. CONCLUSION: VAC therapy was effective and safe in the treatment of complicated pleural empyema. The presence of smaller bronchial stump fistula and of residual lung tissue are not a contraindication for VAC therapy. PMID- 21978621 TI - The mechanism of solvent effect on the positional selectivity of Candida antarctica lipase B during 1,3-diolein synthesis by esterification. AB - We investigated the influence of solvent on the positional selectivity of Novozym 435 which was the immobilized Candida antarctica lipase B (CALB) during the esterification of oleic acid with glycerol for 1,3-diolein preparation previously. Herein, molecular modeling was used to elucidate the underlying mechanism of the solvent effect on the positional selectivity of the enzyme. The results showed that the binding energy of sn-1 hydroxyl of glycerol molecular with CALB became higher, and the binding energy of sn-2 hydroxyl of glycerol molecular with CALB became lower along with the increase of the solvent log P. It was demonstrated that, increasing log P of the solvent, the enzyme selectivity to sn-1 hydroxyl of glycerol molecular grew weaker, and the selectivity to sn-2 hydroxyl of glycerol molecular grew stronger. PMID- 21978622 TI - Organic matter transformations and kinetics during sewage sludge composting in a two-stage system. AB - The use of different proportions of rape straw and grass as amendments in the composting of dewatered sewage sludge from a municipal wastewater treatment plant was tested in a two-stage system (first stage, an aerated bioreactor and second stage, a periodically turned windrow). The composition of feedstock affected the temperature and organic matter degradation in the bioreactor and the formation of humic substances, especially humic acids (HA), during compost maturation in the windrow. The total HA content (the sum of labile and stable HA) increased according to first-order kinetics, whereas labile HA content was constant and did not exceed 12% of total HA. DeltalogK of 1.0-1.1 indicated that HA was of R-type, indicating a low degree of humification. Temperature during composting was the main factor affecting polymerization of fulvic acids to HA and confirmed the value of the degree of polymerization, which increased only when thermophilic conditions were obtained. PMID- 21978623 TI - Kinetic behavior of liquefaction of Japanese beech in subcritical phenol. AB - Non-catalytic liquefaction of Japanese beech (Fagus crenata) wood in subcritical phenol was investigated using a batch-type reaction vessel. After samples were treated at 160 degrees C/0.9 MPa-350 degrees C/4.2 MPa for 3-30 min, they were fractionated into a phenol-soluble portion and phenol-insoluble residues. These residues were then analyzed for their chemical composition. Based on the obtained data, the kinetics for liquefaction was modeled using first-order reaction rate law. Subsequently, the liquefaction rate constants of the major cell wall components including cellulose, hemicellulose, and lignin were determined. The different kinetic mechanisms were found to exist for lignin and cellulose at two different temperature ranges, lower 160-290 degrees C and higher 310-350 degrees C, whereas for hemicellulose, it was only liquefied in the lower temperature range. Thus, the liquefaction behaviors of these major cell wall components highlighted hemicellulose to be the most susceptible to liquefaction, followed by lignin and cellulose. PMID- 21978624 TI - Co-digestion of different waste mixtures from agro-industrial activities: kinetic evaluation and synergetic effects. AB - Several wastes from agro-industrial activities were mixed in different ratios to evaluate the co-digestion process. Methane yield YCH4, specific methanogenic activity (SMA) and a kinetic parameter (k0) were determined. A second feeding was also performed to examine the recovery of bacterial activity after exhaustion. Mixture ratios of 1:1:1:1 and 1:3:4:0.5 (w/w) showed the best performance, with YCH4 of 664; 582 NmL CH4/gVSsubstrate, as well as SMA of 0.12; 0.13 gCODNmLCH4/gVSinoculum/d, respectively, during the digestion of the first feed. It was possible to relate synergetic effects with enhancement in YCH4 by up to 43%, compared with values calculated from YCH4 of the individual substrates. All batches started up the biogas production after an exhaustion period, when a second feed was added. However, long lag phases (up to 21 days) were observed due to stressed conditions caused by the substrate limitation prior to the second feed. PMID- 21978625 TI - Effects of pH and ORP on microbial ecology and kinetics for hydrogen production in continuously dark fermentation. AB - The microbial structure and kinetic characteristics of the hydrogen producing strains in two fermentative continuous stirred-tank reactors (CSTRs) were studied by controlling pH and oxidation and reduction potential (ORP). The fluorescence in situ hybridization (FISH) tests were conducted to investigate the fermentative performance of Clostridium histolyticum (C. histolyticum), Clostridium lituseburense (C. lituseburense) and Enterobacteriaceae. The experimental results showed that in ethanol-type reactor 1#, the relative abundance of the strains was 48%, 30% and 22%. Comparatively, the relative abundance in butyric acid-type reactor 2# was 24%, 55% and 19% with butyric acids and hydrogen as the main products. The kinetic results indicated that the hydrogen yield coefficients YP/X in both reactors were 8.357 and 5.951 l-H2/g, while the coefficients of the cellular yield were 0.0268 and 0.0350 g-Cell/g, respectively. At the same biomass, the hydrogen yield in ethanol-type reactors was more than that in butyric acid reactors. However, the cellular synthesis rate in ethanol-type reactors was low when the same carbon source was used. PMID- 21978626 TI - Four variants in transferrin and HFE genes as potential markers of iron deficiency anaemia risk: an association study in menstruating women. AB - BACKGROUND: Iron deficiency anaemia is a worldwide health problem in which environmental, physiologic and genetic factors play important roles. The associations between iron status biomarkers and single nucleotide polymorphisms (SNPs) known to be related to iron metabolism were studied in menstruating women. METHODS: A group of 270 Caucasian menstruating women, a population group at risk of iron deficiency anaemia, participated in the study. Haematological and biochemical parameters were analysed and 10 selected SNPs were genotyped by minisequencing assay. The associations between genetic and biochemical data were analysed by Bayesian Model Averaging (BMA) test and decision trees. Dietary intake of a representative subgroup of these volunteers (n = 141) was assessed, and the relationship between nutrients and iron biomarkers was also determined by linear regression. RESULTS: Four variants, two in the transferrin gene (rs3811647, rs1799852) and two in the HFE gene (C282Y, H63D), explain 35% of the genetic variation or heritability of serum transferrin in menstruating women. The minor allele of rs3811647 was associated with higher serum transferrin levels and lower transferrin saturation, while the minor alleles of rs1799852 and the C282Y and H63D mutations of HFE were associated with lower serum transferrin levels. No association between nutrient intake and iron biomarkers was found. CONCLUSIONS: In contrast to dietary intake, these four SNPs are strongly associated with serum transferrin. Carriers of the minor allele of rs3811647 present a reduction in iron transport to tissues, which might indicate higher iron deficiency anaemia risk, although the simultaneous presence of the minor allele of rs1799852 and HFE mutations appear to have compensatory effects. Therefore, it is suggested that these genetic variants might potentially be used as markers of iron deficiency anaemia risk. PMID- 21978627 TI - Primary B cell repertoire remodeling to achieve humoral transplantation tolerance. AB - The current mainstay of immunotherapy in clinical transplantation is T lymphocyte directed. However, it has long been appreciated that the emergence of an alloimmune response mounted by the B lymphocyte compartment and detectable as donor-specific antibodies is a critical challenge to long-term graft survival. Thus, achieving robust transplantation tolerance will require induction of tolerance in both the T- and B-cell compartments. Here we propose that the natural developmental propensity of the B-lymphocyte compartment acquisition of tolerance to self-antigens can be recapitulated to achieve humoral transplantation tolerance. It is our contention B-lymphocyte directed induction immunotherapy would be an important component of emerging strategies for induction of Transplantation tolerance. PMID- 21978628 TI - Cerebral oxygenation during subclinical seizures in neonatal hypoxic-ischaemic encephalopathy. AB - Treatment of subclinical seizures in newborn HIE remains a contentious issue, especially in light of potential adverse effects of aggressive use of anticonvulsants. We report on the association of subclinical seizures with changes in cerebral oxygenation in an infant with HIE. Our results show that subclinical seizures of longer durations and with associated autonomic disturbance (increased blood pressure) are more likely to be associated with fluctuation in cerebral oxygenation, with some seizures resulting in cerebral hypoxia. Future studies should aim to delineate the effects of subclinical seizure and anticonvulsant treatment on cerebral oxygenation, and their relationships to developmental outcome. Level of cerebral oxygenation may play a role in refining anti-convulsant treatment and management of subclinical seizures in newborns. PMID- 21978630 TI - Unique single molecule binding of cardiac myosin binding protein-C to actin and phosphorylation-dependent inhibition of actomyosin motility requires 17 amino acids of the motif domain. AB - Cardiac myosin binding protein-C (cMyBP-C) has 11 immunoglobulin or fibronectin like domains, C0 through C10, which bind sarcomeric proteins, including titin, myosin and actin. Using bacterial expressed mouse N-terminal fragments (C0 through C3) in an in vitro motility assay of myosin-generated actin movement and the laser trap assay to assess single molecule actin-binding capacity, we determined that the first N-terminal 17 amino acids of the cMyBP-C motif (the linker between C1 and C2) contain a strong, stereospecific actin-binding site that depends on positive charge due to a cluster of arginines. Phosphorylation of 4 serines within the motif decreases the fragments' actin-binding capacity and actomyosin inhibition. Using the laser trap assay, we observed individual cMyBP-C fragments transiently binding to a single actin filament with both short (~20 ms) and long (~300 ms) attached lifetimes, similar to that of a known actin-binding protein, alpha-actinin. These experiments suggest that cMyBP-C N-terminal domains containing the cMyBP-C motif tether actin filaments and provide one mechanism by which cMyBP-C modulates actomyosin motion generation, i.e. by imposing an effective viscous load within the sarcomere. PMID- 21978631 TI - Hormone therapy and coronary heart disease risk by vasomotor menopausal symptoms. AB - OBJECTIVES: We examined whether the association between hormone therapy (HT) use and coronary heart disease (CHD) risk differed between women with and without vasomotor symptoms (VMS). STUDY DESIGN: We used data from a Dutch (EPOS) and Swedish (WHILA) population-based sample of 8865 women, aged 46-64 years, and free of CHD, stroke, venous thrombosis/pulmonary embolism or cancer at baseline. Data on HT use, VMS and potential confounders were collected by questionnaires. MAIN OUTCOME MEASURES: CHD endpoints, obtained via registries. RESULTS: 252 CHD cases occurred during 10.3 years of follow-up. Neither for women with nor for women without flushing or (night) sweats ever HT use was associated with CHD risk, compared with never HT use. Among women with intense VMS, ever HT use borderline significantly decreased CHD risk compared with never HT use (HR 0.48 [95% CI 0.20 1.03]). Among women without intense VMS, ever HT use was associated with a borderline significant increased CHD risk (HR 1.28 [95% CI 0.96-1.70]; P for interaction=0.02). However, after multivariate adjustment, as compared to never HT use, ever HT use was not associated with risk of CHD among women with or without intense VMS. CONCLUSIONS: In both groups of women with and without VMS, HT use does not seem to be associated with the risk of CHD. Hence, our findings do not support the view that HT use increases the CHD risk among women with an indication, i.e. VMS, but this needs to be confirmed in specifically designed studies. PMID- 21978633 TI - Is unimpeded marketing for breast milk substitutes responsible for the decline in breastfeeding in the Philippines? An exploratory survey and focus group analysis. AB - Infant mortality and morbidity risk is linked to formula usage. The proportion of Filipino infant formula users rose 6% between 2003 and 2008. It is hypothesized this rise resulted from aggressive formula industry marketing. We conducted a household survey between April and December 2006 and focus groups in April-May 2007 in The Philippines to examine the association between mothers' exposure to advertising and other information sources and formula feeding decisions. Sixteen barangays (communities) were randomly selected from three purposively selected disadvantaged rural, urban and mixed municipalities. A total of 345 households had children under 24-months age: 114, 142 and 89 households from the rural, urban and mixed municipalities, respectively. In addition 38 respondents participated in 3 focus groups of 10-15 participants each, from three selected barangays. After adjusting for education and economic indicators logistic regression analysis showed that, children were more likely to be given formula if their mother recalled advertising messages, or a doctor, or mother or relative recommended it. Those using formula were 6.4 (1.8-23.1) times more likely to stop breastfeeding before 12 months. The focus groups described how television advertisements, doctors and medical representatives enticed them to use formula. We conclude that two factors were strongly associated with the decision to formula feed: self-reported advertising exposure, and physicians' recommendations. PMID- 21978632 TI - Distinct signatures of the immune responses in low risk versus high risk neuroblastoma. AB - BACKGROUND: Over 90% of low risk (LR) neuroblastoma patients survive whereas less than 30% of high risk (HR) patients are long term survivors. Age (children younger than 18 months old) is associated with LR disease. Considering that adaptive immune system is well developed in older children, and that T cells were shown to be involved in tumor escape and progression of cancers, we sought to determine whether HR patients may tend to show a signature of adaptive immune responses compared to LR patients who tend to have diminished T-cell responses but an intact innate immune response. METHODS: We performed microarray analysis of RNA extracted from the tumor specimens of HR and LR patients. Flow cytometry was performed to determine the cellular constituents in the blood while multiplex cytokine array was used to detect the cytokine profile in patients' sera. A HR tumor cell line, SK-N-SH, was also used for detecting the response to IL-1beta, a cytokines which is involved in the innate immune responses. RESULTS: Distinct patterns of gene expression were detected in HR and LR patients indicating an active T-cell response and a diminished adaptive immune response, respectively. A diminished adaptive immune response in LR patients was evident by higher levels of IL-10 in the sera. In addition, HR patients had lower levels of circulating myeloid derived suppressor cells (MDSC) compared with a control LR patient. LR patients showed slightly higher levels of cytokines of the innate immune responses. Treatment of the HR tumor line with IL-1beta induced expression of cytokines of the innate immune responses. CONCLUSIONS: This data suggests that adaptive immune responses may play an important role in the progression of HR disease whereas innate immune responses may be active in LR patients. PMID- 21978629 TI - Metabolic stress, reactive oxygen species, and arrhythmia. AB - Cardiac arrhythmias can cause sudden cardiac death (SCD) and add to the current heart failure (HF) health crisis. Nevertheless, the pathological processes underlying arrhythmias are unclear. Arrhythmic conditions are associated with systemic and cardiac oxidative stress caused by reactive oxygen species (ROS). In excitable cardiac cells, ROS regulate both cellular metabolism and ion homeostasis. Increasing evidence suggests that elevated cellular ROS can cause alterations of the cardiac sodium channel (Na(v)1.5), abnormal Ca(2+) handling, changes of mitochondrial function, and gap junction remodeling, leading to arrhythmogenesis. This review summarizes our knowledge of the mechanisms by which ROS may cause arrhythmias and discusses potential therapeutic strategies to prevent arrhythmias by targeting ROS and its consequences. This article is part of a Special Issue entitled "Local Signaling in Myocytes". PMID- 21978634 TI - Mississippi front-line recovery work after Hurricane Katrina: an analysis of the intersections of gender, race, and class in advocacy, power relations, and health. AB - By disrupting the routine practices and social structures that support social hierarchy, disasters provide a unique opportunity to observe how gender, race, and class power relations are enacted and reconstituted to shape health inequities. Using a feminist intersectional framework, we examine the dynamic relationships among a government/corporate alliance, front-line disaster recovery workers, and disadvantaged residents in Mississippi Gulf Coast communities in the aftermath of Hurricane Katrina, which struck in August, 2005. Data were collected between January 2007 and October 2008 through field observations, public document analysis, and in-depth interviews with 32 front-line workers representing 27 non governmental, nonprofit community-based organizations. Our analysis reveals how power relationships among these groups operated at the macro-level of the political economy as well as in individual lives, increasing health risks among both the disadvantaged and the front-line workers serving and advocating on their behalf. Socially situated as outsiders-within, front-line recovery workers operated in the middle ground between the disadvantaged populations they served and the powerful alliance that controlled access to essential resources. From this location, they both observed and were subject to the processes guiding the allocation of resources and their unequal outcomes. Following a brief period of hope for progressive change, recovery workers became increasingly stressed and fatigued, particularly from lack of communication and coordination, limited resources, insufficient capacity to meet overwhelming demands, and gendered and racialized mechanisms of marginalization and exclusion. The personal and collective health burdens borne by these front-line recovery workers- predominantly women and people of color - exemplify the ways in which the social relations of power and control contribute to health and social inequities. PMID- 21978635 TI - Regulation of formula advertising in the Philippines and promotion and protection of breastfeeding: a commentary on Sobel, Iellamo, Raya, Padilla, Olive and Nyunt U. PMID- 21978636 TI - Screen-based sedentary behaviours among a nationally representative sample of youth: are Canadian kids couch potatoes? AB - PURPOSE: To determine the percentage of Canadian youth meeting screen-time guidelines and to identify characteristics associated with different screen-time behaviours. METHODS: Using nationally representative data collected from the 2008/2009 Youth Smoking Survey (YSS), we analyzed three screen-time behaviours, cigarette smoking, weekly spending money, self esteem, region and grade by sex, and conducted four logistic regression models to examine factors associated with more than 2 hours a day of sedentary screen time. RESULTS: Of 51 922 Canadian youth in grades 6 to 12, 50.9% spent more than 2 hours per day in screen-based behaviours. The average daily screen time was 7.8 (+/- 2.3) hours. Males and current smokers were more likely to report over 2 hours per day watching TV and videos or playing video games, whereas students in higher grades and those with weekly spending money were more likely to report playing or surfing on a computer. Youth with higher self-esteem were less likely to report spending over 2 hours per day in each of the three screen-time behaviours examined. CONCLUSION: Developing a better understanding of the factors associated with more hours of screen time is required to develop and target interventions that reduce screen time behaviours. PMID- 21978637 TI - Priority issues in occupational cancer research: Ontario stakeholder perspectives. AB - INTRODUCTION: Workers are potentially exposed to known and suspected carcinogens in the workplace, many of which have not been fully evaluated. Despite persistent need, research on occupational cancer appears to have declined in recent decades. The formation of the Occupational Cancer Research Centre (OCRC) is an effort to counter this downward trend in Ontario. The OCRC conducted a survey of the broad stakeholder community to learn about priority issues on occupational cancer research. METHODS: The OCRC received 177 responses to its survey from academic, health care, policy, industry, and labour-affiliated stakeholders. Responses were analyzed based on workplace exposures, at-risk occupations and cancers by organ system, stratified by respondents' occupational role. DISCUSSION: Priority issues identified included workplace exposures such as chemicals, respirable dusts and fibres (e.g. asbestos), radiation (e.g. electromagnetic fields), pesticides, and shift work; and occupations such as miners, construction workers, and health care workers. Insufficient funding and a lack of exposure data were identified as the central barriers to conducting occupational cancer research. CONCLUSION: The results of this survey underscore the great need for occupational cancer research in Ontario and beyond. They will be very useful as the OCRC develops its research agenda. PMID- 21978638 TI - A review of screening mammography participation and utilization in Canada. AB - INTRODUCTION: Participation rate is an important indicator for a screening program's effectiveness; however, the current approach to measuring participation rate in Canada is not comparable with other countries. The objective of this study is to review the measurement of screening mammography participation in Canada, make international comparisons, and propose alternative methods. METHODS: Canadian breast cancer screening program data for women aged 50 to 69 years screened between 2004 and 2006 were extracted from the Canadian Breast Cancer Screening Database (CBCSD). The fee-for-services (FSS) mammography data (opportunistic screening mammography) were obtained from the provincial ministries of health. Both screening mammography program participation and utilization were examined over 24 and 30 months. RESULTS: Canada's screening participation rate increases from 39.4% for a 24-month cut-off to 43.6% for a 30 month cut-off. The 24-month mammography utilization rate is 63.1% in Canada, and the 30-month utilization rate is 70.4%. CONCLUSION: Due to the differences in health service delivery among Canadian provinces, both programmatic participation and overall utilization of mammography at 24 months and 30 months should be monitored. PMID- 21978639 TI - The prevalence of chronic pain and pain-related interference in the Canadian population from 1994 to 2008. AB - INTRODUCTION: Estimates of the prevalence of chronic pain worldwide and in Canada are inconsistent. Our primary objectives were to determine the prevalence of chronic pain by sex and age and to determine the prevalence of pain-related interference for Canadian men and women between 1994 and 2008. METHODS: Using data from seven cross-sectional cycles in the National Population Health Survey and the Canadian Community Health Survey, we defined two categorical outcomes, chronic pain and pain-related interference with activities. RESULTS: Prevalence of chronic pain ranged from 15.1% in 1996/97 to 18.9% in 1994/95. Chronic pain was most prevalent among women (range: 16.5% to 21.5%), and in the oldest (65 years plus) age group (range: 23.9% to 31.3%). Women aged 65 years plus consistently reported the highest prevalence of chronic pain (range: 26.0% to 34.2%). The majority of adult Canadians who reported chronic pain also reported at least a few activities prevented due to this pain (range: 11.4% to 13.3% of the overall population). CONCLUSION: Similar to international estimates, this Canadian population-based study confirms that chronic pain persists and impacts daily activities. Further study with more detailed definitions of pain and pain related interference is warranted. PMID- 21978640 TI - Can we use medical examiners' records for suicide surveillance and prevention research in Nova Scotia? AB - INTRODUCTION: Medical examiners' records can contribute to our understanding of the extent of suicide in a population, as well as associated sociodemographic and other factors. METHODS: Using a mixed methods approach, the key objective of this pilot study was to determine the sources and types of information found in the Nova Scotia Medical Examiner Service (NSMES) records that might inform suicide surveillance and targeted prevention efforts. A secondary objective was to describe the one-year cohort of 108 individuals who died by suicide in 2006 in terms of available sociodemographic information and health care use in the year prior to death. RESULTS: Data extraction revealed inconsistencies both across and within files in terms of the types and amounts of sociodemographic and other data collected, preventing correlational analyses. However, linkage of the records to administrative databases revealed frequent health care use in the month prior to death. CONCLUSION: The introduction of systematic data collection to NSMES investigations may yield a comprehensive dataset useful for policy development and population level research. PMID- 21978641 TI - Online resources to enhance decision-making in public health. AB - A virtual front door, the Canadian Best Practices Portal for Health Promotion and Chronic Disease Prevention ("the Portal") provides access to evaluated community and population health interventions relevant to chronic disease prevention and health promotion. Designed to help Canadian public health practitioners and decision makers identify suitable interventions that they can adapt and replicate to meet their needs, the Portal is a highly accessible, easy to use and dynamic. It has a flexible search function and is supported by an extensive array of resources to inform policy and practice. Launched in 2006, the Portal forms a central pillar of the Canadian Best Practices Initiative, which was established by the Public Health Agency of Canada (PHAC) to improve policy and program decision-making by enabling access to the best available evidence on chronic disease prevention and health promotion practices. Throughout each phase of the Portal's development, more and more current public health topics and new decision making tools have been added. As of February 2011, the Portal provides information on about 357 interventions and access to 58 resources. In this article, we aim to demonstrate the unique role of the Portal within the broader context of other available online resources. We use the concept of a "pyramid of evidence" to compare the Portal with one specific resource, Health-evidence.ca, to illustrate how public health practitioners and decision makers can use these resources together to make better, more evidence-informed decisions. PMID- 21978642 TI - Association of surgeons in training conference--Sheffield 2011. PMID- 21978643 TI - Role of tyrosyl-DNA phosphodiesterase 1 and inter-players in regulation of tumor cell sensitivity to topoisomerase I inhibition. AB - Tyrosyl-DNA phosphodiesterase 1 (TDP1) plays a unique function as it catalyzes the repair of topoisomerase I-mediated DNA damage. Thus, ovarian carcinoma cell lines exhibiting increased TDP1 levels and resistance to the topoisomerase I poisons campthotecins were used to clarify the role of this enzyme. The camptothecin gimatecan was employed as a tool to inhibit topoisomerase I because it produces a persistent damage. The resistant sublines displayed an increased capability to repair drug-induced single-strand breaks and a reduced amount of drug-induced double-strand breaks, which was enhanced following TDP1 silencing. In loss of function studies using U2-OS cells, we found that TDP1 knockdown did not produce a change in sensitivity to camptothecin, whereas co-silencing of other pathways cooperating with TDP1 in cell response to topoisomerase I poisons indicated that XRCC1 and BRCA1 were major regulators of sensitivity. No change in cellular sensitivity was observed when TDP1 was silenced concomitantly to RAD17, which participates in the stabilization of collapsed replication forks. The expression of dominant-negative PARP1 in cells with reduced expression of TDP1 due to a constitutively expressed TDP1 targeting microRNA did not modulate cell sensitivity to camptothecin. Mild resistance to gimatecan was observed in cells over-expressing TDP1, a feature associated with decreased levels of drug-induced single-strand breaks. In conclusion, since TDP1 alone can account for mild levels of camptothecin resistance, repair of topoisomerase I-mediated DNA damage likely occurs through redundant pathways mainly implicating BRCA1 and XRCC1, but not RAD17 and PARP1. These findings may be relevant to define novel therapeutic strategies. PMID- 21978644 TI - Administration of resveratrol: What formulation solutions to bioavailability limitations? AB - Resveratrol (3,5,4'-trihydroxystilbene), a naturally occurring polyphenol, has attracted considerable interest for its beneficial potentials for human health, which include anti-oxidant, anti-inflammatory, cardioprotective and anti-tumor activities. However, the in vivo biological effects of resveratrol appear strongly limited by its low bioavailability, which is a barrier to the development of therapeutic applications. In this context, an increasing number of recent studies have aimed at designing novel resveratrol formulations to overcome its poor solubility, limited stability, high metabolization and weak bioavailability. This review outlines physicochemical and pharmacokinetic limitations to resveratrol bioavailability, describes formulations tested for resveratrol administration, controlled release and targeting, and identifies future opportunities for resveratrol delivery. PMID- 21978645 TI - Nanocomposite microparticles for injectable cell scaffolds. PMID- 21978646 TI - Postlaryngectomy dysphagia masking as velopharyngeal insufficiency: a simple solution for an anterior neopharyngeal diverticulum. AB - Postlaryngectomy dysphagia is a common occurrence and can be a source of emotional distress that results in a decrease in quality of life among a patient population that is already exposed to considerable morbidity. One etiologic source that is less commonly reported as a source for postlaryngectomy dysphagia, and perhaps overlooked, is an anterior neopharyngeal diverticulum. Herein, we describe a postlaryngectomy dysphagia caused by a neopharyngeal diverticulum masking as velopharyngeal insufficiency of liquids. The liquid dysphagia was immediately relieved via transoral endoscopic approach using the Harmonic scalpel to resect and simultaneously coagulate the posterior wall. PMID- 21978647 TI - Nasal septal angiofibroma, a subclass of extranasopharyngeal angiofibroma. AB - OBJECTIVE: Extranasopharyngeal angiofibromas (ENA) arising from the nasal septum or nasal septal angiofibromas are extremely rare; only 13 such cases have been reported in the international literature. Our objective is to describe the presentation, workup, and surgical management of these lesions. STUDY DESIGN: Case reports were done. SETTING: The setting was a tertiary care referral center and the Veterans Affairs Medical Center. PATIENTS, INTERVENTIONS, AND RESULTS: We present 2 cases of extranasopharyngeal angiofibroma occurring on the nasal septum. CONCLUSIONS: In this report, we discuss the occurrence, the histopathologic findings, and the treatment of nasal septal angiofibroma. PMID- 21978648 TI - Benign paroxysmal positional vertigo after use of noise-canceling headphones. AB - Benign paroxysmal positional vertigo (BPPV) is a common cause of vertigo. We describe a case of a woman presenting acutely with a severe episode of disabling positional vertigo. Although she had no known etiologic risk factors, this attack followed 12 hours of continuously wearing digital noise-canceling headphones. This is the first such reported association between BPPV and the use of this gadget. We also provide a short review of BPPV and speculate on the possible pathogenic mechanisms involved. PMID- 21978649 TI - Human CD8+ T cells display a differential ability to undergo cytokine-driven bystander activation. AB - A subset of CD44(hi)CD8+ T cells in some, but not all mice, can be induced to rapidly secrete IFNgamma during infection with Listeria monocytogenes. This response is dependent on the presence of both IL-12 and IL-18 and does not require engagement of the T cell receptor. In this study, we demonstrate that human CD8+ T cells also vary widely in their ability to secrete IFNgamma within 15h of either Listeria infection or cytokine stimulation. The magnitude of the rapid IFNgamma response correlated more closely with the intrinsic responsiveness of the T cells to cytokine stimulation rather than the amount of IL-12 produced. CD8+ T cells from 2 out of 16 blood donors (12.5%) failed to generate a significant IFNgamma response. These results demonstrate that bystander activation of CD8+ T cells varies among individuals and validate further study of the differential responses observed using BALB/c vs. C57BL/6 mice. PMID- 21978650 TI - Functional abnormality of the auditory brainstem in high-risk late preterm infants. AB - OBJECTIVE: To examine whether late preterm infants with perinatal problems are at risk of brainstem auditory impairment. METHODS: 68 high-risk late preterm infants (gestation 33-36 weeks) with perinatal problems or conditions were studied at term using maximum length sequence brainstem auditory evoked response. The controls were 41 normal term infants and 37 low-risk late preterm infants. RESULTS: Compared with normal term infants, the high-risk late preterm infants demonstrated a significant abnormal increase in MLS BAER variables that mainly reflect more central function of the brainstem auditory pathway, including wave V latency, III-V and I-V interpeak intervals, and III-V/I-III interval ratio. The abnormalities were more significant at higher than at lower click rates. The slopes of MLS BAER-rate function for these variables were increased. Compared with low-risk late preterm infants, the high-risk infants showed similar, though slightly less significant, abnormalities, mainly a significant increase in III-V and I-V intervals. CONCLUSIONS: Maximum length sequence brainstem auditory evoked response components that mainly reflect central function of the auditory brainstem were abnormal at term in high-risk late preterm infants. SIGNIFICANCE: More central regions of the auditory brainstem are impaired in high-risk late preterm infants, which is mainly caused by associated perinatal problems or conditions. PMID- 21978651 TI - Do age-related changes contribute to the flanker effect? AB - OBJECTIVES: The present study examined age-related changes in the flanker effect and the extent to which age interacts with flanker-induced differences in perceptual processing, which contribute to the flanker effect. METHODS: We adopted a modified flanker-task paradigm that incorporates PRO (i.e., hand responses correspond to target arrows) and ANTI (i.e., hand responses do not correspond to target arrows) conditions. Participants from two age groups searched for a centrally presented target flanked on each side by stimuli that were associated with either the same response as the target (congruent), the opposite response (incongruent), or neither response (neutral). Event-related potentials (ERPs), lateralized readiness potentials (LRPs), and behavioral performance were measured. RESULTS: The behavioral-data results showed that a typical flanker effect was present in both age groups in PRO and ANTI conditions, suggesting that flanker-induced differences in perceptual processing contributed to the flanker effect in a similar manner for both age groups. Furthermore, no increase in flanker interference was observed in older adults. LRP profiles also provided convergent evidence showing that perceptually based flanker effects were similar for both age groups. CONCLUSIONS: The present study suggests that aging does not increase flanker interference, nor does it alter perceptually based flanker interference. SIGNIFICANCE: The present study found that older adults could be just as capable as younger adults in resolving flanker interference by adopting different strategies to compensate for their deficiencies. PMID- 21978652 TI - Emergent EEG in the emergency department in patients with altered mental states. AB - OBJECTIVE: To evaluate whether EEG performed within 30 min of referral by an ED physician helps establish diagnosis and/or changes management and in which clinical setting. METHODS: Single-center prospective cohort intervention study 1 day/week, of sequentially referred adult patients with clinical seizures or altered mental status (AMS). Standard EEGs were performed by an EEG technician using a commercially available cap, interpreted by an epileptologist, immediately reported to the ED physician and a utility survey completed. Quality and interpretation of 20 min EEGs was compared to pre-specified 5 min segments of each EEG using the kappa coefficient. RESULTS: Over 1 year, 82 patients underwent ED EEG. Tonic clonic seizure activity had occurred in 33%. Mean time for EEG setup was 13.1 +/- 6.2 min. EEG assisted the diagnosis in 51%, changed ED management in 4% and would be ordered again if EEG was available in 46%. Positive utility of EEG was significantly associated with toxicologic, psychiatric and endocrine/metabolic causes of AMS vs. other causes (p<0.001) and sudden onset AMS (p=0.007). Independent predictors of whether ED EEG would be ordered if available were witnessed seizures (p=0.01), no prior head trauma (p=0.001) and survey respondent being a physician assistant (vs. MD) (p=0.02). The 5 (vs. 20) min EEG presented good agreement on waveform shape/amplitude (kappa=0.78), artifact (kappa=0.75) and interpretation categories (all kappa levels >= 0.70). CONCLUSIONS: Rapid availability of standard full-montage EEG in the ED is feasible and helps establish a diagnosis in about half of AMS patients, but rarely changes management. An abbreviated 5 min full-montage EEG presents adequate reliability which may improve use in the ED. SIGNIFICANCE: Specific presentations of AMS offer the best diagnostic benefit for EEG in the ED. PMID- 21978654 TI - Does anodal transcranial direct current stimulation enhance excitability of the motor cortex and motor function in healthy individuals and subjects with stroke: a systematic review and meta-analysis. AB - The primary aim of this review is to evaluate the effects of anodal transcranial direct current stimulation (a-tDCS) on corticomotor excitability and motor function in healthy individuals and subjects with stroke. The secondary aim is to find a-tDCS optimal parameters for its maximal effects. Electronic databases were searched for studies into the effect of a-tDCS when compared to no stimulation. Studies which met the inclusion criteria were assessed and methodological quality was examined using PEDro and Downs and Black (D&B) assessment tools. Data from seven studies revealed increase in corticomotor excitability with a small but significant effect size (0.31 [0.14, 0.48], p=0.0003) in healthy subjects and data from two studies in subjects with stroke indicated significant results with moderate effect size (0.59 [0.24, 0.93], p=0.001) in favor of a-tDCS. Likewise, studies examining motor function demonstrated a small and non-significant effect (0.39 [-0.17, 0.94], p=0.17) in subjects with stroke and a large but non significant effect (0.92 [-1.02, 2.87], p=0.35) in healthy subjects in favor of improvement in motor function. The results also indicate that efficacy of a-tDCS is dependent on current density and duration of application. A-tDCS increases corticomotor excitability in both healthy individuals and subjects with stroke. The results also show a trend in favor of motor function improvement following a tDCS. A-tDCS is a non-invasive, cheap and easy-to-apply modality which could be used as a stand-alone technique or as an adds-on technique to enhance corticomotor excitability and the efficacy of motor training approaches. However, the small sample size of the included studies reduces the strength of the presented evidences and any conclusion in this regard should be considered cautiously. PMID- 21978653 TI - Tremor reduction and modeled neural activity during cycling thalamic deep brain stimulation. AB - OBJECTIVE: The effectiveness of deep brain stimulation (DBS) depends on both the frequency and the temporal pattern of stimulation. We quantified responses to cycling DBS with constant frequency to determine if there was a critical on and/or off time for alleviating tremor. METHODS: We measured postural tremor in 10 subjects with thalamic DBS and quantified neuronal entropy in a network model of Vim thalamic DBS. We tested 12 combinations of cycling on/off times that maintained the same average frequency of 125 Hz, four constant frequency settings, and baseline. RESULTS: Tremor and neural firing pattern entropy decreased as the percent on time increased from 50% to 100%. Cycling with stimulation on for at least 60% of the time was as effective as regular stimulation. All cycling settings reduced the firing pattern entropy of model neurons from the no stimulation condition by regularizing pathological firing patterns, either through synaptically-mediated inhibition or axon excitation. CONCLUSIONS: These results indicate that pauses present in cycling stimulation decreased its effectiveness in suppressing tremor, and that changes in the amount of tremor suppression were strongly correlated with changes in the firing pattern entropy of model neurons. SIGNIFICANCE: Cycling stimulation may reduce power consumption during clinical DBS, and thereby increase the battery life of the implanted pulse generator. PMID- 21978655 TI - Ocular vestibular evoked myogenic potential (oVEMP) responses in acute vestibular neuritis. PMID- 21978656 TI - Characterization of Streptococcus thermophilus two-component systems: In silico analysis, functional analysis and expression of response regulator genes in pure or mixed culture with its yogurt partner, Lactobacillus delbrueckii subsp. bulgaricus. AB - The lactic acid bacterium Streptococcus thermophilus (S. thermophilus) is widely used in the dairy industry. As a food bacterium, it has to cope with changing environments such as milk, yogurt, as well as the digestive tract, after the product has been ingested. In bacteria, two-component systems (TCS) are one of the most prevalent mechanisms to sense and respond appropriately to a wide range of signals. They are typically composed of a sensor kinase (HK) that detects a stimulus and a response regulator (RR) which acts as a transcriptional regulator. Our objective was to make an inventory of the TCS present in S. thermophilus LMD 9 and investigate the contribution of each TCS to LMD-9 growth in milk. For that purpose, we performed in silico, transcriptomic as well as functional analysis. The LMD-9 genome presented 6 complete TCS with both HK and RR (TCS 2, 4, 5, 6, 7, and 9) and 2 orphan RRs (RR01 and 08) with truncated HK. Our in silico analysis revealed that for 5 TCS out of the 8, orthologs with known functions were found in other bacterial species whereas for TCS02, 4 and 6 the function of the orthologs are unidentified. Transcriptomic studies (using quantitative PCR) revealed that all S. thermophilus LMD-9 response regulator genes were expressed in milk; they were expressed at different levels and with different profiles during growth. In mixed culture with Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus), the S. thermophilus partner in yogurt, the expression of four S. thermophilus LMD-9 response regulator increased; two of them, rr02 and rr09, increased by a factor of 6. These results indicate that the presence of L. bulgaricus induces regulatory changes in S. thermophilus. We also demonstrated that a response regulator (rr02) can exert its regulatory function on its target genes even when expressed at very low levels. We showed that RR05-an ortholog of Bacillus subtilis YycF or Staphylococcus aureus WalR-was essential for the growth of S. thermophilus. For the 7 other RRs, the absence of a single response regulator gene was insufficient to notably impact the growth of LMD-9 in milk, with or without supplementation with purines, formate, or stress agents (lactate, H2O2). We demonstrated here that the 8 response regulators of LMD-9 are expressed -and thus potentially active--during growth in milk and suggested that the response regulators have possibly overlapping regulons and/or functions not essential under the conditions tested. PMID- 21978657 TI - RE-PCR variability and toxigenic profile of food poisoning, foodborne and soil associated Bacillus cereus isolates from Brazil. AB - Twenty-three Bacillus cereus isolates from food poisoning outbreaks associated with a diarrheal-type syndrome, fourteen foodborne isolates not associated with food poisoning and fifteen isolates from Brazilian soil samples were analyzed for the presence and genetic diversity (by RE-PCR) of the virulence genes ces (emetic toxin, cereulide), plcR-papR (pleiotropic regulator PlcR and peptide PapR), nheA (a component of the NHE complex), bceT (diarrheal enterotoxin bc-D-ENT), gyrB (B subunit of DNA gyrase), cytK-2 (necrotic enterotoxin cytotoxin K-2), and plcA (phosphatidylcholine-specific phospholipase C). Additionally, these isolates were phenotypically characterized for motility, hemolytic and lecithinase activities, as well as HBL enterotoxin production. The group of isolates associated with food poisoning had the highest occurrence of the phenotypically analyzed factors and the most frequent occurrence and highest genetic diversity of the plcR-papR, nheA, bceT, cytK-2, plcA, and gyrB genes. An analysis of molecular variance (AMOVA), in which all loci were analyzed, demonstrated that the genetic variation intragroup of isolates (92%) was significantly higher than that intergroup (8%) (P<0.05). These results were corroborated by an analysis of the genetic differentiation between the groups, which was low/moderate, the result of a high degree of allele sharing. Our results suggest that B. cereus isolates with the potential to cause food poisoning outbreaks do not have a specific genetic profile characterized by the presence of a particular gene or allele among the genes assessed. On the contrary, different combinations of genes encoding virulence factors may be present in different isolates of B. cereus that potentially cause food poisoning outbreaks. PMID- 21978658 TI - Microparticle number or procoagulant activity are not upregulated in healthy elderly persons. PMID- 21978659 TI - Prosthetic valve endocarditis caused by Staphylococcus capitis: report of 4 cases. AB - Although Staphylococcus capitis is considered to be a rare causative organism for prosthetic valve endocarditis, we report 4 such cases that were encountered at our hospital over the past 2 years. Case 1 was a 79-year-old woman who underwent aortic valve replacement with a bioprosthetic valve and presented with fever 24 days later. Transesophageal echocardiography revealed an annular abscess in the aorto-mitral continuity and mild perivalvular regurgitation. We performed emergency surgery 5 days after the diagnosis of prosthetic valve endocarditis was made. Case 2 was a 79-year-old woman presenting with fever 40 days after aortic valve replacement with a bioprosthesis. Transesophageal echocardiography showed vegetation on the valve, and she underwent urgent surgery 2 days after prosthetic valve endocarditis was diagnosed. In case 3, a 76-year-old man presented with fever 53 days after aortic valve replacement with a bioprosthesis. Vegetation on the prosthetic leaflet could be seen by transesophageal echocardiography. He underwent emergency surgery 2 days after the diagnosis of prosthetic valve endocarditis was made. Case 4 was a 68-year-old woman who collapsed at her home 106 days after aortic and mitral valve replacement with bioprosthetic valves. Percutaneous cardiopulmonary support was started immediately after massive mitral regurgitation due to prosthetic valve detachment was revealed by transesophageal echocardiography. She was transferred to our hospital by helicopter and received surgery immediately on arrival. In all cases, we re-implanted another bioprosthesis after removal of the infected valve and annular debridement. All patients recovered without severe complications after 2 months of antibiotic treatment, and none experienced re-infection during 163 to 630 days of observation. Since the time interval between diagnosis of prosthetic valve endocarditis and valve re-replacement ranged from 0 to 5 days, early surgical removal of the infected prosthesis and an appropriate course of antibiotics were attributed to good clinical outcomes in our cases. PMID- 21978660 TI - Depression, glycemic control and type 2 diabetes. AB - BACKGROUND: Comorbid depression in diabetes has been suggested as one of the possible causes of an inadequate glycemic control. The purpose of this study was to investigate the association between major depression and the glycemic control of type 2 diabetes mellitus (T2DM). METHODS: Seventy T2DM patients were evaluated. They underwent a psychiatric examination using the following instruments: Structured Clinical Interview for DSM-IV and Beck Depression Inventory. The diabetes status was assessed in the short-term (glycemia, glycated hemoglobin) clinical control. RESULTS: The presence of current depression was observed in 18.6% (13/70). In addition, type 2 diabetes patients who displayed depression evidenced higher levels of glycated hemoglobin (8.6 +/- 2.0 vs. 7.5 +/ 1.8; p = 0.05) when compared to those who did not exhibit a mood disorder. CONCLUSIONS: In our sample, the presence of depression seems to impact on the short-term control of T2DM. The authors discuss the clinical utility of these findings in the usual treatment of diabetes. PMID- 21978661 TI - Nonselective excitation of pulsed ELDOR using multi-frequency microwaves. AB - The use of a polychromatic microwave pulse to expand the pumping bandwidth in pulsed electron-electron double resonance (PELDOR) was investigated. The pumping pulse was applied in resonance with the broad (~100 mT) electron paramagnetic resonance (EPR) signal of the manganese cluster of photosystem II in the S2 state. The observation pulses were in resonance with the narrow EPR signal of the tyrosine radical, YD.. It was found that in the case of the polychromatic pumping pulse containing five harmonics with the microwave frequencies between 8.5 and 10.5 GHz the PELDOR effect corresponding to the dipole interaction between the Mn cluster and YD. was about 2.9 times larger than that achieved with a monochromatic pulse. In addition to the dipolar modulation, the nuclear modulation effects were observed. The effects could be suppressed by averaging the PELDOR trace over the time interval between the observation microwave pulses. The polychromatic excitation technique described will be useful for improving the PELDOR sensitivity in the measurements of long distances in biological samples, where the pair consists of a radical with a narrow EPR spectrum and slow phase relaxation, and a metal center that has a broad EPR spectrum and a short phase relaxation time. PMID- 21978662 TI - 14N quadrupole resonance and 1H T1 dispersion in the explosive RDX. AB - The explosive hexahydro-1,3,5-trinitro-s-triazine (CH2-N-NO2)3, commonly known as RDX, has been studied by 14N NQR and 1H NMR. NQR frequencies and relaxation times for the three nu+ and nu- lines of the ring 14N nuclei have been measured over the temperature range 230-330 K. The 1H NMR T1 dispersion has been measured for magnetic fields corresponding to the 1H NMR frequency range of 0-5.4 M Hz. The results have been interpreted as due to hindered rotation of the NO2 group about the N-NO2 bond with an activation energy close to 92 kJ mol(-1). Three dips in the 1H NMR dispersion near 120, 390 and 510 kHz are assigned to the nu0, nu- and nu+ transitions of the 14NO2 group. The temperature dependence of the inverse line-width parameters T2* of the three nu+ and nu- ring nitrogen transitions between 230 and 320 K can be explained by a distribution in the torsional oscillational amplitudes of the NO2 group about the N-NO2 bond at crystal defects whose values are consistent with the latter being mainly edge dislocations or impurities in the samples studied. Above 310 K, the 14N line widths are dominated by the rapid decrease in the spin-spin relaxation time T2 due to hindered rotation of the NO2 group. A consequence of this is that above this temperature, the 1H T1 values at the quadrupole dips are dominated by the spin mixing time between the 1H Zeeman levels and the combined 1H and 14N spin-spin levels. PMID- 21978663 TI - The prevalence and management of low back pain across adulthood: results from a population-based cross-sectional study (the MUSICIAN study). AB - The aim of the current study was to determine: the prevalence of low back pain (LBP) and associated disability; the frequency of consultation to general practice; whether there were differences in management by age. We conducted a cross-sectional population study in Aberdeen city and Cheshire County, UK. Participants were 15,272 persons aged 25 years and older. The 1-month period prevalence of LBP was 28.5%. It peaked at age 41-50 years, but at ages over 80 years was reported by 1 in 4 persons. Older persons were more likely to consult, and the prevalence of severe LBP continued to increase with age. Management by general practitioners differed by age of the patient. Older persons (> 70 vs <= 40 years) were more likely to only have been prescribed painkillers (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.28-2.35) or only pain killers with other medications (OR 1.45, 95% CI 1.07-1.98). They were less likely to be prescribed physiotherapy or exercise (OR 0.63, 95% CI 0.46-0.85) or to be referred to a specialist (OR 0.77, 95% CI 0.57-1.04). Older persons were more likely to have previously received exercise therapy for pain, were less likely to be enthusiastic about receiving it now (P<0.0001), and were less likely to think it would result in improved symptoms (P<0.0001). It is important that older persons, who have the highest prevalence of LBP with disability and are most likely to consult, are receiving optimal pharmacological and nonpharmacological management. PMID- 21978665 TI - The C0C1 fragment of human cardiac myosin binding protein C has common binding determinants for both actin and myosin. AB - The N-terminal domains of cardiac myosin binding protein C (MyBP-C) play a regulatory role in modulating interactions between myosin and actin during heart muscle contraction. Using NMR spectroscopy and small-angle neutron scattering, we have determined specific details of the interaction between the two-module human C0C1 cMyBP-C fragment and F-actin. The small-angle neutron scattering data show that C0C1 spontaneously polymerizes monomeric actin (G-actin) to form regular assemblies composed of filamentous actin (F-actin) cores decorated by C0C1, similar to what was reported in our earlier four-module mouse cMyBP-C actin study. In addition, NMR titration analyses show large intensity changes for a subset of C0C1 peaks upon addition of G-actin, indicating that human C0C1 interacts specifically with actin and promotes its assembly into filaments. During the NMR titration, peaks corresponding to cardiac-specific C0 domain are the first to be affected, followed by those from the C1 domain. No peak intensity or position changes were detected for peaks arising from the disordered proline/alanine-rich (P/A) linker connecting C0 with C1, despite previous suggestions of its involvement in binding actin. Of considerable interest is the observation that the actin-interaction "hot-spots" within the C0 and C1 domains, revealed in our NMR study, overlap with regions previously identified as binding to the regulatory light chain of myosin and to myosin DeltaS2. Our results suggest that C0 and C1 interact with myosin and actin using a common set of binding determinants and therefore support a cMyBP-C switching mechanism between myosin and actin. PMID- 21978664 TI - Heparin activates PKR by inducing dimerization. AB - Protein kinase R (PKR) is an interferon-induced kinase that plays a pivotal role in the innate immunity pathway. PKR is activated to undergo autophosphorylation upon binding to double-stranded RNAs or RNAs that contain duplex regions. Activated PKR phosphorylates the alpha subunit of eukaryotic initiation factor 2, thereby inhibiting protein synthesis. PKR is also activated by heparin, a highly sulfated glycosaminoglycan. We have used biophysical methods to define the mechanism of PKR activation by heparin. Heparins as short as hexasaccharide bind strongly to PKR and activate autophosphorylation. In contrast to double-stranded RNA, heparin activates PKR by binding to the kinase domain. Analytical ultracentrifugation measurements support a thermodynamic linkage model where heparin binding allosterically enhances PKR dimerization, thereby activating the kinase. These results indicate that PKR can be activated by small molecules and represents a viable target for the development of novel antiviral agents. PMID- 21978666 TI - Structural model for p75(NTR)-TrkA intracellular domain interaction: a combined FRET and bioinformatics study. AB - Nerve growth factor (NGF) is a member of the neurotrophins, which are important regulators of embryonic development and adult function in the vertebrate nervous systems. The signaling elicited by NGF regulates diverse activities, including survival, axon growth, and synaptic plasticity. NGF action is mediated by engagement with two structurally unrelated transmembrane receptors, p75(NTR) and TrkA, which are co-expressed in a variety of cells. The functional interactions of these receptors have been widely demonstrated and include complex formation, convergence of signaling pathways, and indirect interaction through adaptor proteins. Each domain of the receptors was shown to be important for the formation of TrkA and p75(NTR) complexes, but only the intramembrane and transmembrane domains seemed to be crucial for the creation of high-affinity binding sites. However, whether these occur through a physical association of the receptors is unclear. In the present work, we demonstrate by Forster resonance energy transfer that p75(NTR) and TrkA are physically associated through their intracellular (IC) domains and that this interaction occurs predominantly at the cell membrane and prior to NGF stimulation. Our data suggest that there is a pool of receptors dimerized before NGF stimulus, which could contribute to the high affinity binding sites. We modeled the three-dimensional structure of the TrkA IC domain by homology modeling, and with this and the NMR-resolved structure of p75(NTR), we modeled the heterodimerization of TrkA and p75(NTR) by docking methods and molecular dynamics. These models, together with the results obtained by Forster resonance energy transfer, provide structural insights into the receptors' physical association. PMID- 21978667 TI - Conservation of lipid functions in cytochrome bc complexes. AB - Lipid binding sites and properties are compared in two sub-families of hetero oligomeric membrane protein complexes known to have similar functions in order to gain further understanding of the role of lipid in the function, dynamics, and assembly of these complexes. Using the crystal structure information for both complexes, we compared the lipid binding properties of the cytochrome b(6)f and bc(1) complexes that function in photosynthetic and respiratory membrane energy transduction. Comparison of lipid and detergent binding sites in the b(6)f complex with those in bc(1) shows significant conservation of lipid positions. Seven lipid binding sites in the cyanobacterial b(6)f complex overlap three natural sites in the Chlamydomonas reinhardtii algal complex and four sites in the yeast mitochondrial bc(1) complex. The specific identity of lipids is different in b(6)f and bc(1) complexes: b(6)f contains sulfoquinovosyldiacylglycerol, phosphatidylglycerol, phosphatidylcholine, monogalactosyldiacylglycerol, and digalactosyldiacylglycerol, whereas cardiolipin, phosphatidylethanolamine, and phosphatidic acid are present in the yeast bc(1) complex. The lipidic chlorophyll a and beta-carotene (beta-car) in cyanobacterial b(6)f, as well as eicosane in C. reinhardtii, are unique to the b(6)f complex. Inferences of lipid binding sites and functions were supported by sequence, interatomic distance, and B-factor information on interacting lipid groups and coordinating amino acid residues. The lipid functions inferred in the b(6)f complex are as follows: (i) substitution of a transmembrane helix by a lipid and chlorin ring, (ii) lipid and beta-car connection of peripheral and core domains, (iii) stabilization of the iron-sulfur protein transmembrane helix, (iv) n-side charge and polarity compensation, and (v) beta-car-mediated super-complex with the photosystem I complex. PMID- 21978668 TI - The NLRP12 pyrin domain: structure, dynamics, and functional insights. AB - The initial line of defense against infection is sustained by the innate immune system. Together, membrane-bound Toll-like receptors and cytosolic nucleotide binding domain and leucine-rich repeat-containing receptors (NLR) play key roles in the innate immune response by detecting bacterial and viral invaders as well as endogenous stress signals. NLRs are multi-domain proteins with varying N terminal effector domains that are responsible for regulating downstream signaling events. Here, we report the structure and dynamics of the N-terminal pyrin domain of NLRP12 (NLRP12 PYD) determined using NMR spectroscopy. NLRP12 is a non-inflammasome NLR that has been implicated in the regulation of Toll-like receptor-dependent nuclear factor-kappaB activation. NLRP12 PYD adopts a typical six-helical bundle death domain fold. By direct comparison with other PYD structures, we identified hydrophobic residues that are essential for the stable fold of the NLRP PYD family. In addition, we report the first in vitro confirmed non-homotypic PYD interaction between NLRP12 PYD and the pro-apoptotic protein Fas-associated factor 1 (FAF-1), which links the innate immune system to apoptotic signaling. Interestingly, all residues that participate in this protein:protein interaction are confined to the alpha2-alpha3 surface, a region of NLRP12 PYD that differs most between currently reported NLRP PYD structures. Finally, we experimentally highlight a significant role for tryptophan 45 in the interaction between NLRP12 PYD and the FAF-1 UBA domain. PMID- 21978669 TI - Cardiovascular magnetic resonance activity in the United Kingdom: a survey on behalf of the British Society of Cardiovascular Magnetic Resonance. AB - BACKGROUND: The indications, complexity and capabilities of cardiovascular magnetic resonance (CMR) have rapidly expanded. Whether actual service provision and training have developed in parallel is unknown. METHODS: We undertook a systematic telephone and postal survey of all public hospitals on behalf of the British Society of Cardiovascular Magnetic Resonance to identify all CMR providers within the United Kingdom. RESULTS: Of the 60 CMR centres identified, 88% responded to a detailed questionnaire. Services are led by cardiologists and radiologists in equal proportion, though the majority of current trainees are cardiologists. The mean number of CMR scans performed annually per centre increased by 44% over two years. This trend was consistent across centres of different scanning volumes. The commonest indication for CMR was assessment of heart failure and cardiomyopathy (39%), followed by coronary artery disease and congenital heart disease. There was striking geographical variation in CMR availability, numbers of scans performed, and distribution of trainees. Centres without on site scanning capability refer very few patients for CMR. Just over half of centres had a formal training programme, and few performed regular audit. CONCLUSION: The number of CMR scans performed in the UK has increased dramatically in just two years. Trainees are mainly located in large volume centres and enrolled in cardiology as opposed to radiology training programmes. PMID- 21978670 TI - [Study of nasopharyngeal colonization by Streptococcus pneumoniae and its antibiotics resistance in healthy children less than 2 years of age in the Marrakech region (Morocco)]. AB - The healthy carrier of Streptococcus pneumoniae (S. pneumoniae) has been studied very little at the national level. With the emergence of antibiotic-resistant strains worldwide, and the emergence of new serotypes, an epidemiological survey is needed before the vaccine can be introduced in Morocco. OBJECTIVES: This study's objective was to determine the prevalence and risk factors of pneumococcal nasopharyngeal carriage in children less than 2 years of age in the Marrakech region and to assess the antibiotic susceptibility of the isolates and the serotypes present prior to the introduction of the conjugate pneumococcal vaccine. PATIENTS AND METHODS: From 2008 to 2009, 660 nasopharyngeal samples were collected on children under 2 years of age during scheduled visits to dispensaries for routine immunization in the Marrakech region. RESULTS: S. pneumoniae carriage was found in 45.8% of children. Of the 660 samples, 302 strains were isolated. The percentage of pneumococcal strains with reduced susceptibility to penicillin (PRSP) was 34.7%. Among these strains, 87.1% showed low-level resistance and 12.9% high-level resistance. Resistance to amoxicillin was found in 3.3% of the strains and no strains were resistant to cefotaxime. Several risk factors for pneumococcal carriage were identified, the main ones being breastfeeding less than 2 months, the presence of more than one sibling, passive smoking, and low socioeconomic level. The most frequent serotypes were 19F, 6, 14, 23, 18, and 9. The study of the vaccine serotype distribution showed that the theoretical vaccine coverage of the 7 valent vaccines was at 57% for all the isolates. CONCLUSION: These data show the frequency and the risk factors on nasopharyngeal carriage, and report the status of penicillin resistance of strains carrying children less than 2 years of age in the Marrakech region. The fluctuation of circulating serotypes at the national level underscores the importance of epidemiological surveillance carried out before the introduction of the heptavalent vaccine in Morocco. PMID- 21978671 TI - UPR in palmitate-treated pancreatic beta-cells is not affected by altering oxidation of the fatty acid. AB - BACKGROUND: Elevated levels of lipids are detrimental for beta-cell function and mass. One of the mechanisms of how fatty acids induce apoptosis is development of the unfolded protein response (UPR). It is still far from understood how fatty acids activate the UPR, however. METHODS: We examined how palmitate-induced activation of the UPR was affected by altering the metabolism of the fatty acid in insulin-secreting INS-1E and MIN6 cell lines and intact human islets. To increase oxidation, we used low glucose (5.5 mM) or AICAR; and to reduce oxidation, we used high glucose (25 mM) or etomoxir. UPR was measured after 3, 24 and 48 hours of palmitate treatment. RESULTS: Modulation of palmitate oxidation by either glucose or the pharmacological agents did not affect palmitate-induced UPR activation. CONCLUSION: Our finding suggests that other factors than oxidation of palmitate play a role in the activation of UPR in fatty acid-treated beta-cells. PMID- 21978672 TI - Synthesis and preliminary evaluation of amiloride analogs as inhibitors of the urokinase-type plasminogen activator (uPA). AB - A known side-activity of the oral potassium-sparing diuretic drug amiloride is inhibition of the enzyme urokinase-type plasminogen activator (uPA, K(i)=7 MUM), a promising anticancer target. Several studies have demonstrated significant antitumor/metastasis properties for amiloride in animal cancer models and it would appear that these arise, at least in part, through inhibition of uPA. Selective optimization of amiloride's structure for more potent inhibition of uPA and loss of diuretic effects would thus appear as an attractive strategy towards novel anticancer agents. The following report is a preliminary structure-activity exploration of amiloride analogs as inhibitors of uPA. A key finding was that the well-studied 5-substituted analogs ethylisopropyl amiloride (EIPA) and hexamethylene amiloride (HMA) are approximately twofold more potent than amiloride as uPA inhibitors. PMID- 21978673 TI - Design, synthesis, and biological activity of a novel series of 2,5-disubstituted furans/pyrroles as HIV-1 fusion inhibitors targeting gp41. AB - Based on molecular docking analysis of earlier results, we designed a series of 2,5-disubstituted furans/pyrroles (5a-h) as HIV-1 entry inhibitors. Compounds were synthesized by Suzuki-Miyaura cross coupling, followed by a Knoevenagel condensation or Wittig reaction. Four of these compounds were found to be effective in inhibiting HIV-1 infection, with the best compounds being 5f and 5h, which exhibited significant inhibition on HIV-1(IIIB) infection at micromolar levels with low cytotoxicity. These compounds are also effective in blocking HIV 1 mediated cell-cell fusion and the gp41 six-helix bundle formation, suggesting that they are also HIV-1 fusion inhibitors targeting gp41 and have potential to be developed as a new class of anti-HIV-1 agents. PMID- 21978674 TI - Synthesis and antioxidant activities of novel 4-Schiff base-7-benzyloxy-coumarin derivatives. AB - 4-Schiff base-7-benzyloxy-coumarins 5a(1)-5h(2) and its derivative 6 were designed and synthesized based on the 7-benzyloxy-coumarin structure as novel antioxidants. The in vitro antioxidant activities screening revealed that 2,2 diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities of compounds 5b(1), 5d(1), 5f(1), 5f(2), 5g(1) and 5g(2), and 2,2'-azinobis-(3 ethylbenzthiazoline-6-sulfonate) cation (ABTS(+)) radical scavenging activities of compounds 5a(1), 5b(1), 5c(1), 5c(2), 5d(1), 5e(1), 5e(2), 5f(2), 5g(1), 5g(2) and 5h(1) were better than that of the commercial antioxidant butylated hydroxytoluene (BHT), while the superoxide anion radical scavenging activities of 5a(2) and 5g(2) were stronger than that of the commercial antioxidant butylated hydroxyanisole (BHA), and the hydroxyl radical scavenging activity of 5e(1) was much better than that of the common antioxidant ascorbic acid. PMID- 21978675 TI - Discovery of highly potent small molecule Hepatitis C Virus entry inhibitors. AB - Novel, highly potent small molecule HCV entry inhibitors are reported. The SAR exploration of a hit molecule identified from screening of a compound library led to the identification of highly potent compounds with IC(50) values of <5 nM in the tissue culture HCV infectious assay. PMID- 21978676 TI - Inhibitory effect on NO production of phenolic compounds from Myristica fragrans. AB - Three new phenolics: ((7S)-8'-(benzo[3',4']dioxol-1'-yl)-7-hydroxypropyl)benzene 2,4-diol (1), ((7S)-8'-(4'-hydroxy-3'-methoxyphenyl)-7-hydroxypropyl)benzene-2,4 diol (2) and ((8R,8'S)-7-(4-hydroxy-3-methoxyphenyl)-8'-methylbutan-8-yl)-3' methoxybenzene-4',5'-diol (3), along with four known compounds (4-7) were isolated from the seeds of Myristica fragrans. Their chemical structures were established mainly by 1D and 2D NMR techniques and mass spectrometry. Their anti inflammatory activity was evaluated against LPS-induced NO production in macrophage RAW264.7 cells. PMID- 21978677 TI - Investigating the role of the hydroxyl groups of substrate erythrose 4-phosphate in the reaction catalysed by the first enzyme of the shikimate pathway. AB - 3-Deoxy-D-arabino-heptulosonate 7-phosphate (DAH7P) synthase catalyses the first step of the shikimate pathway, which is responsible for the biosynthesis of aromatic amino acids in microorganisms and plants. This enzyme catalyses an aldol reaction between phosphoenolpyruvate and D-erythrose 4-phosphate to generate DAH7P. Both 2-deoxyerythrose 4-phosphate and 3-deoxyerythrose 4-phosphate were synthesised and tested as alternative substrates for the enzyme. Both compounds were found to be substrates for the DAH7P synthases from Escherichia coli, Pyrococcus furiosus and Mycobacterium tuberculosis, consistent with an acyclic mechanism for the enzyme for which neither C2 nor C3 hydroxyl groups are required for catalysis. The enzymes all showed greater tolerance for the loss of the C2 hydroxyl group than the C3 hydroxyl group. PMID- 21978678 TI - Synthesis and radioligand binding studies of bis-(8-isopropyl-isoquinolinium) derivatives as ligands for apamin-sensitive sites on cloned SK2 and SK3 channels. AB - A structure-activity relationship study of N-methyl-laudanosine, a SK channel blocker, has indicated that the 6,7-dimethoxy group could be successfully replaced by a hydrophobic moiety such as an isopropyl substituent in position 8 of the isoquinoline ring. In the present study, bis-(8-isopropyl-isoquinolinium) derivatives (2a-e) were synthesized and tested for their affinity for cloned SK2 and SK3 channels in comparison with their 6,7-dimethoxy analogues (4a-f). Several ligands were investigated, both in flexible (propyl, butyl and pentyl) and rigid (m- or p-xylyl) series, the m-xylyl derivative (2d) having the best profile in terms of affinity and selectivity for SK3/SK2 channels. Molecular studies showed that the optimal conformation of compound 2d fits well with our SK pharmacophore model. PMID- 21978679 TI - 4-N-Hydroxy-4-[1-(sulfonyl)piperidin-4-yl]-butyramides as HDAC inhibitors. AB - A series of N-substituted 4-alkylpiperidine hydroxamic acids, corresponding to the basic structure of histone deacetylase (HDAC) inhibitors (zinc binding moiety linker-capping group) has been previously reported by our group. Linker length and aromatic capping group connection were systematically varied to find the optimal geometric parameters. A new series of submicromolar inhibitors was thus identified, which showed antiproliferative activity on HCT-116 colon carcinoma cells. We report here the second part of the strategy used in our research group to find a new class of HDAC inhibitors, namely the SAR study for the compounds bearing a sulfonyl group on the piperidine nitrogen. In the present work, we have considered both sulfonamides and sulfonyl ureas. PMID- 21978680 TI - Structural requirement of phenylthiourea analogs for their inhibitory activity of melanogenesis and tyrosinase. AB - Effect of a series of 1-phenylthioureas 1a-k and 1,3-disubstituted thioureas 2a-k were evaluated against melanin formation in melanoma B16 cell line and mushroom tyrosinase. Inhibitory activity of tyrosinase of 1-phenylthioureas 1a-k is parallel to their melanogenic inhibition. Thus, the melanogenic inhibition in melanoma B16 cells of 1-phenylthioureas could be the result of inhibition of tyrosinase. However, 1,3-diaryl or 1-phenyl-3-alkylthioureas, 2a-k, appears as melanogenic inhibitor without inhibition of tyrosinase. The molecular docking study of 1e and 2b to binding pocket of tyrosinase provided convincing explanation regarding the necessity of direct connection of planar phenyl to thiourea unit without N'-substitution of phenylthioureas 1 as tyrosinase inhibitor and 2 as non-tyrosinase inhibitor. PMID- 21978681 TI - Pt-rotaxanes as cytotoxic agents. AB - Cytotoxic agents that specifically target cancer cells are in high demand. Modifying drugs with targeting groups however, can produce deleterious effects on drug pharmokinetics. In this study, platinum (Pt) was linked with host-rotaxanes to discover the effect on the cytotoxicity of Pt when carried by a highly modified rotaxane as a ligand. One host-rotaxane (Pt-BocRot) contains the basic components of a rotaxane: wheel (with a Boc protecting group), axle, and blocking group. A second rotaxane (Pt-ArgRot) contains arginine moieties on its wheel instead to potentially improve association with the phosphate groups on cell membranes or DNA backbone. The cytotoxicities of the rotaxanes and various model compounds were determined using ovarian cancer SKOV-3 cell line, which is resistant to cisplatin. We found Pt-ArgRot was slightly more cytotoxic than Pt BocRot. Both were clearly more cytotoxic than rotaxanes without Pt and the model compounds. As importantly, they killed cells through an apoptotic mechanism. These results suggest that targeting agents for a particular cell type can be incorporated with Pt-complexes using the rotaxane architecture to improve drug specificity. PMID- 21978682 TI - Synthesis and antibacterial activity of N4-mono alkyl derivatives of novel glycopeptide LYV07ww01. AB - Thirty-one N(4)-mono alkyl derivatives of novel glycopeptide LYV07ww01 were synthesized by the reductive alkylation and their in vitro antibacterial activity was tested. The benzyl derivatives showed potent activity, especially against vancomycin-resistant enterococci and penicillin-resistant Streptococcus pneumoniae. PMID- 21978683 TI - Discovery and SAR exploration of a novel series of imidazo[4,5-b]pyrazin-2-ones as potent and selective mTOR kinase inhibitors. AB - We report here the discovery of a novel series of selective mTOR kinase inhibitors. A series of imidazo[4,5-b]pyrazin-2-ones, represented by screening hit 1, was developed into lead compounds with excellent mTOR potency and exquisite kinase selectivity. Potent compounds from this series show >1000-fold selectivity over the related PI3Kalpha lipid kinase. Further, compounds such as 2 achieve mTOR pathway inhibition, blocking both mTORC1 and mTORC2 signaling, in PC3 cancer cells as measured by inhibition of pS6 and pAkt (S473). PMID- 21978684 TI - Effects of the 2003 European heatwave on the benthic community of a severe transitional ecosystem (Comacchio Saltworks, Italy). AB - The summer of 2003 was the warmest summer in Europe since the 16th century. Its consequences on the fauna of a transitional ecosystem were studied through biodiversity, functional and ecological indicators, from summer 2002 to winter 2005. The heatwave caused considerable changes in the benthic community structure and relative composition, persisting in 2005. Animal assemblages switched from mollusc- to annelida-dominated. Biodiversity and functional indicators captured changes in community structure and composition, proving to be powerful tools to detect responses related to global warming. Ecological indicators rendered a monotonic response oscillating between bad and poor ecological status across the study period. The resilience of mollusc biocoenosis resulted limited with respect to other taxa, posing concerns about their conservation if, as predicted, the frequency of summers as hot as that of 2003 will progressively increase to become the norm at the end of this century. PMID- 21978685 TI - A bioindicator system for water quality on inshore coral reefs of the Great Barrier Reef. AB - Responses of bioindicator candidates for water quality were quantified in two studies on inshore coral reefs of the Great Barrier Reef (GBR). In Study 1, 33 of the 38 investigated candidate indicators (including coral physiology, benthos composition, coral recruitment, macrobioeroder densities and FORAM index) showed significant relationships with a composite index of 13 water quality variables. These relationships were confirmed in Study 2 along four other water quality gradients (turbidity and chlorophyll). Changes in water quality led to multi faceted shifts from phototrophic to heterotrophic benthic communities, and from diverse coral dominated communities to low-diversity communities dominated by macroalgae. Turbidity was the best predictor of biota; hence turbidity measurements remain essential to directly monitor water quality on the GBR, potentially complemented by our final calibrated 12 bioindicators. In combination, this bioindicator system may be used to assess changes in water quality, especially where direct water quality data are unavailable. PMID- 21978686 TI - Transcriptional profile of denervated vastus lateralis muscle derived from a patient 8 months after spinal cord injury: a case-report. AB - A lack of motor neurons abolishes both neurotrophic factor secretion and contractile activity in muscle, which impairs mass, contractile properties, and fibre-type characteristics of the muscle. However, the molecular pathways that can be stimulated or repressed in the scenario of spinal cord injury remain unknown. We investigated for the first time the transcriptional profile of a young male patient 8 months after spinal cord injury. Adaptive metabolic changes of complete denervated skeletal muscle were revealed. In particular, the main molecular pathways involved include metabolic and proteolitic pathways, mitochondrial and synaptic function, calcium homeostasis, sarcomere and anchorage structures. Our data depict the molecular signalling still present in complete denervated skeletal muscle fibres a few months after spinal cord injury. These data could be of interest also to design a specific therapeutic approach aimed at the electrical-stimulation of severe atrophied skeletal muscle. PMID- 21978687 TI - TLR2: a crossroads between infections and autoimmunity? AB - Environment has both pathogenic and protective roles in the determination of autoimmune disease development, possibly through infectious agents. TLR2 has the capability to recognize the widest range of PAMPs, and it is important for the recognition of mycobacteria and gram-positive bacteria. Here we review recent information showing that TLR2 ligands, its signaling machinery and the effects of its engagement on T cell polarization and differentiation, all play a decisive role in experimental models of autoimmunity. Thus, we propose that engagement of TLR2 is an important crossroad between encounter with bacteria and development of self-reactive diseases. PMID- 21978688 TI - Peri-implant diseases and host inflammatory response involving mast cells: a review. AB - Mast cells (MCs) are motile granule-containing cells that originate from bone marrow pluripotential haematopoietic cells, circulate in blood and extravasate in tissues where they play an important role in inflammation, host defense and tissue repair. We herein review the English literature over the past twenty years concerning the biology and function of MCs with particular focus on their role in the inflammatory process in dental implant failure due to osseointegration absence or to peri-implantitis. Due to immunological or non-immunological stimulation, in a few minutes MCs release prestored granule-associated mediators into the extracellular environment promoting pro-/anti-inflammatory events/response. MCs can either protect the host by activating defense mechanisms and initiating tissue repair and osseointegration if their function is transient, or lead to considerable tissue damage if it is inappropriate and continuous leading to osseointegration absence or peri-implantitis. We hypothesize that administration of histamine receptor antagonists, serine protease inhibitors and MC preformed mediator release inhibitors before and after implantation could represent novel therapeutic strategies to improve the osseointegration, the functionality and longevity of implants or prevent and treat peri-implant inflammatory conditions. PMID- 21978689 TI - Cholesterol, cytokines and diseases. AB - A high level of cholesterol is associated with obesity, cardiovascular diseases and atherosclerosis. Immune response in atherosclerosis is mediated by chemokines which attract monocytes, leading to the innate immune response characterised by the production of cytokines. The immunoregulatory cytokines are an important bridge between innate and adductive immunity. TH1 cytokines are involved as effector T cells in inflammatory response, while TH2 cytokines can be anti inflammatory such as IL-10 and IL-4. It is well known that statins enhance the production of TH2 cytokines whereas the secretion of TH1 cytokines is suppressed. For this purpose, we studied the significance of anti-inflammatory effect and suppression of inflammation by statins. In this paper we revisited the role of cholesterol and cytokines IL-18, IL-10, IL-12, TNF-alpha, interferon-gamma, and chemokines in inflammatory diseases. PMID- 21978690 TI - A novel monoclonal antibody against human CD80 and its immune protection in a mouse lupus-like disease. AB - Blockade of the interactions between CD28/CTLA-4 and their ligands, CD80 (B7, B7.1)/CD86 (B70, B7.2), is an attractive means to induce antigen-specific peripheral tolerance in autoimmune disease and organ transplantation. In this study, we generated and characterized a monoclonal antibody (Clone 4E5) against human CD80. 4E5 could recognize both human and mouse CD80 and suppress mixed lymphocyte reaction in vitro. To investigate their potency for clinical use, we further administrated 4E5 to a mouse lupus-like disease model (C57BL/J6) induced by Pristane. 4E5 could inhibit the immune response and attenuate the severity of lupus-like disease. The data showed 4E5 function and suggested that blockade of CD80/CD28 co-stimulatory signal pathway with 4E5 is a promising strategy to decelerate the progression of lupus-like disease and other autoimmune diseases. PMID- 21978692 TI - p53 and BCL-2 over-expression inversely correlates with histological differentiation in occupational ethmoidal intestinal-type sinonasal adenocarcinoma. AB - Despite their histological resemblance to colorectal adenocarcinoma, there is little information on the molecular events involved in the pathogenesis of intestinal-type sinonasal adenocarcinoma (ITACs). The aim of this paper is to evaluate the possible role of TP53 and Bcl-2 gene defects in ITAC by investigating the immunohistochemical expression of TP53 and Bcl-2 gene products in a group of ethmoidal ITACs associated with occupational exposure. A retrospective study on 15 patients with pathological diagnosis of primary ethmoidal ITAC was conducted. Representative formalin-fixed, paraffin wax embedded block from each case was selected for immunohistochemical studies using the antibodies against p53 and Bcl-2. Clinical-pathological data were also correlated with the staining results. The results of immunohistochemical examination demonstrated that poorly differentiated cases showed a higher percentage of p53 and Bcl-2 expressing cells in comparison to well-differentiated cases. No correlation was found with other clinico-pathological parameters, including T, stage and relapses. The relationship between up-regulation of p53 and Bcl-2 and poorly differentiated ethmoidal adenocarcinoma suggests a role of these genes, in combination with additional genetic events, in the pathogenesis of ITAC. PMID- 21978691 TI - Attenuation of expression of extracellular matrix genes with siRNAs to Sparc and Ctgf in skin fibroblasts of CTGF transgenic mice. AB - Transgenic mice that over-express connective tissue growth factor (CTGF) in fibroblasts under the control of an enhancer/promoter element of the Col1a2 gene (Col1a2-CTGF) recapitulate multiorgan fibrosis similar to fibrosis observed in Scleroderma (SSc). In this study we investigate the regulation of secreted protein acidic and rich in cysteine (Sparc) and Ctgf siRNAs on the expression of several extracellular matrix components in the fibroblasts derived from Col1a2 CTGF transgenic mice. Three fibroblast lines were obtained from each of wide type C57BL/6 and CTGF transgenic C57BL/6, and were transfected with Sparc siRNA or Ctgf siRNA. Real-time quantitative RT-PCR and Western blotting were used to examine the transcription and protein levels of type I collagen, CTGF and SPARC. Student's t-tests were used to determine the significance of the results. Our results showed that Col1a2 and Ctgf increased expression at both transcriptional and translational levels in the fibroblasts from the Col1a2-CTGF transgenic mice compared with those in the fibroblasts from their normal wild-type littermate. The treatment with Sparc siRNA or Ctgf siRNA attenuated the mRNA and/or protein expression of the Col1a2, Ctgf and Sparc in these fibroblasts. Sparc and Ctgf siRNAs also showed a reciprocal inhibition at transcript levels. Therefore, our results indicated that both SPARC and CTGF appeared to be involved in the same biological pathway, and they have the potential to serve as a therapeutic target for fibrotic diseases such as SSc. PMID- 21978693 TI - Essential amino acid supplementation decreases liver damage induced by chronic ethanol consumption in rats. AB - The liver sustains the greatest damage from ethanol (EtOH) abuse. EtOH and its metabolites impair hepatocyte metabolism, causing intracellular accumulation of proteins and lipids and increasing radical oxygen species production. These processes are toxic to the mitochondrial respiratory chain and to mitochondrial DNA. We have recently shown that supplementating the diet of rodents with an essential amino acid-enriched mixture (EAAem) significantly increases mitochondrial mass and number in cardiac and skeletal muscles and improves mitochondrial function in aged animals. Thus, in this study we sought to test whether EAAem supplementation could reduce EtOH-induced liver damage. Groups of adult male Wistar rats were fed a standard diet and water ad libitum (the control group), drinking water with 20 percent EtOH (the EtOH group), or drinking water with 20 percent EtOH and EAAem supplementation (1.5 g/kg/day) (the EtOH+EAAem group) for 2 months. The blood EtOH concentration was measured, and markers for fat (Oil-Red-O), mitochondria (Grp75, Cyt-c-ox), endoplasmic reticulum (Grp78), and inflammation (Heme Oxigenase 1, iNOS, and peroxisomes) were analyzed in the liver of animals in the various experimental groups. EAAem supplementation in EtOH-drinking rats ameliorated EtOH-induced changes in liver structure by limiting steatosis, recruiting more mitochondria and peroxisomes mainly to perivenous hepatocytes, stimulating or restoring antioxidant markers, limiting the expression of inflammatory processes, and reducing ER stress. Taken together, these results suggest that EAAem supplementation may represent a promising strategy to prevent and treat EtOH-induced liver damage. PMID- 21978694 TI - HCG hastens both the development of mammary carcinoma and the metastatization of HCG/LH and ERBB-2 receptor-positive cells in mice. AB - Breast cancer is more frequent in human nulliparae, whereas its incidence is reduced by early fullterm pregnancy. Rodent studies suggest that chorionic gonadotropin secretion during pregnancy affords protection by inducing breast structure differentiation. Opposite effects, however, have been observed in cancer prone transgenic mice overexpressing the beta subunit of chorionic gonadotropin or pituitary luteinic hormone (LH). Here we assessed the effect of administration of human chorionic gonadotropin (hCG) for 21 days (corresponding to the duration of a mouse pregnancy) in virgin female mice transgenic for the activated rat (r-) ERBB-2 oncogene (BALB-neuT). In these mice, the onset of atypical mammary duct hyperplasia and its progression towards multiple mammary carcinomas is accelerated by hCG. hCG enhances the in vitro proliferation and in vivo metastatization of tumor cells from a BALB-neuT mammary tumor expressing the hCG/LH as well as the ERBB-2 receptors. These findings suggest that hCG favours the growth and progression of hCG/LH and ERBB-2 receptor-positive breast tumors. PMID- 21978695 TI - Inducing-apoptotic activity of the ethanol extract of Duchesnea indica Focke on treatment of herpes simplex encephalitis. AB - This study explores the inducing-apoptotic activity of the ethanol extract of Duchesnea indica Focke on treatment of herpes simplex encephalitis. Cell models were employed and divided into 4 groups: normal group, virus group, Duchesnea indica group and dexamethasone group. Cytopathic effect examination was employed to detect apoptosis of PC-12 and BV-2 cells. ELISA was used to measure TNF-alpha, IL-1beta, and Greiss method to measure NO secretion. Flow cytometry assay for caspase-3 expressions was performed. As a result, the ethanol extract of Duchesnea indica could protect the neuron cell model from impairment by virus. In the cell model of microglia stimulated by herpes simplex virus (HSV), with the ethanol extract intervention, TNF-alpha, IL-1beta and NO levels were significantly decreased and cell death of BV-2 cells were markedly increased. The expression level of caspase-3 was notably elevated after the extract intervention. In conclusion, the ethanol extract of Duchesnea indica can reduce HSV-induced inflammatory injury on neuron due to the induction of microglia apoptosis. PMID- 21978696 TI - Gene expression profile of human colon cancer cells treated with cross-reacting material 197, a diphtheria toxin non-toxic mutant. AB - Cross-Reacting Material 197 (CRM197) is a diphtheria toxin non-toxic mutant that has shown antitumor activity in mice and humans. It is still unclear whether this anti-tumorigenic effect depends on its strong inflammatory-immunological property, its ability to inhibit heparin-binding epidermal growth factor (HB EGF), or even its possible weak toxicity. CRM197 is utilized as a specific inhibitor of HB-EGF that competes for the epidermal growth factor receptor (EGFR), overexpressed in colorectal cancer and implicated in its progression. In this study we evaluate the effects of CRM197 on HT-29 human colon cancer cell line behaviour and, for CRM197 recognized ability to inhibit HB-EGF, its possible influence on EGFR activation. In particular, while HT-29 does not show any reduction of viability after CRM197 treatment (MTT modified assay), or changes in cell cycle distribution (flow cytometry), in EGFR localization, phospho-EGFR detected signals (immunohistochemistry) or in morphology (scanning electron microscopy, SEM) they show a change in the gene expression profile by microarray analysis (cDNA microarray SS-H19k8). The overexpression of genes like protein phosphatase 2, catalytic subunit, alpha isozyme (PPP2CA), guanine nucleotide binding protein G subunit alpha-1(GNAI1) and butyrophilin, subfamily 2, member A1 (BTN2A1) has been confirmed with real-time-qPCR. This is the first study where the CRM197 treatment on HT-29 shows a possible scarce implication of endogenous HB-EGF on EGFR expression and cancer cell development. At the same time, our results show the alteration of a specific and selected number of genes. PMID- 21978697 TI - Detection of respiratory viruses in the 2009 winter season in Rome: 2009 influenza A (H1N1) complications in children and concomitant type 1 diabetes onset. AB - We investigated clinical characteristics and complications, particularly type 1 diabetes onset, in children hospitalized for 2009 pandemic influenza A (H1N1) virus and compared number of consultations, rate of hospitalization and virus identification in children hospitalized for acute respiratory symptoms (ARS) during the winter season 2009-2010 and 2004-2005. Patients were tested for 2009 H1N1 virus and 14 respiratory viruses on pharyngeal brush/nasal aspirates, using a RT-PCR or nested PCR assays. Consultations and hospitalizations were extracted from operative system GIPSE. The total number of consultations increased by 12%, consultation rate for ARS by 13% and number of hospitalizations by 56% from 2004 2005 to 2009-2010. In 2004-2005, Influenza A virus was identified in only 7 percent of hospitalized children, while in 2009-2010 the 2009 H1N1 virus was identified in 21%. Three children attending the hospital for ARS and 2009 H1N1 infection had ketoacidosis as the onset manifestation of type 1 diabetes. By comparing the number of new diabetes diagnoses among the two winter seasons, we found a higher number of new diagnoses in October 2009-January 2010 than in the same period in 2004-2005 (19 vs 10). Six children (13%), all presenting with pre existing diseases, were admitted to the pediatric intensive care unit. No children died. The outbreak of this novel virus has increased pediatric consultation rates and hospitalizations compared with previous winters without causing deaths. The children at highest risk for severe infection are those with comorbidities. The 2009 H1N1 virus seems in some way involved in the pathogenesis of type 1 diabetes. PMID- 21978698 TI - A new anti-infective strategy to reduce adhesion-mediated virulence in Staphylococcus aureus affecting surface proteins. AB - Staphylococcus aureus is a flexible microbial pathogen frequently isolated from community-acquired and nosocomial infections. The use of indwelling medical devices is associated with a significant risk of infection by this bacterium which possesses a variety of virulence factors, including many toxins, and the ability to invade eukaryotic cells or to form biofilm on biotic and abiotic surfaces. The present study evaluates the anti-infective properties of serratiopeptidase, a secreted protein of Serratia marcescens, in impairing virulence-related staphylococcal properties, such as attachment to inert surfaces and adhesion/invasion on eukaryotic cells. SPEP seems to exert its action by modulating specific proteins. Proteomic studies performed on surface proteins extracted from SPEP-treated S. aureus cultures revealed that a number of proteins are affected by the treatment. Among these we found the adhesin/autolysin Atl, FnBP-A, SecA1, Sbi, EF-Tu, EF-G, and alpha-enolase. EF-Tu, EF-G and alpha-enolase are known to perform a variety of functions, depending on their cytoplasmic or surface localization. All these factors can facilitate bacterial colonization, persistence and invasion of host tissues. Our results suggest that SPEP could be developed as a potential anti-infective agent capable to hinder the entry of S. aureus into human tissues, and also impair the ability of this pathogen to form biofilm on prostheses, catheters and medical devices. PMID- 21978699 TI - An Italian study on health-related quality of life and fatigue in patients with chronic fatigue syndrome and patients with chronic HCV virus infection: similarities and differences. AB - Severe fatigue and a significantly reduced health-related quality of life (HRQoL) have been described in patients with chronic fatigue syndrome (CFS) in comparison with patients affected by chronic hepatitis C (CHC) and other chronic medical conditions. We examined 39 CFS and 49 CHC patients to explore whether fatigue and a poor HRQoL represent a greater medical and social problem in CFS than in CHC. The severity of fatigue and the HRQoL were assessed using the Fatigue Impact Scale (FIS) and the Health Status Questionnaire Short Form-36 (SF-36), respectively. The statistical analysis showed both a higher score of fatigue and a lower HRQoL in CFS than in CHC patients. Furthermore, in CHC patients the FIS evaluation showed a significantly reduced score of the psychosocial domain in comparison with the other domains. Multivariate linear regression analysis revealed female gender as the most important positive variable in chronic hepatitis C patients for total score of FIS. In conclusion, CFS was associated with a severe and disabling fatigue and an impaired HRQOL. In particular, both fatigue and all aspects of HRQOL perceived by CFS patients were significantly impaired compared to CHC patients. Consequently, management of fatigue should be considered a priority in order to improve HRQOL in CFS patients. In CHC patients the impact of fatigue on HRQoL was less significant than in CFS patients, even though the FIS evaluation showed a significant impairment of the psychosocial domain. PMID- 21978700 TI - Peripheral blood neutrophil granulocytes from patients with head and neck squamous cell carcinoma functionally differ from their counterparts in healthy donors. AB - Solid tumors such as head and neck squamous cell carcinoma (HNSCC) display an intense interaction between tumoral factors and the immune system. Functional modulation of tumor-infiltrating and peripheral blood immune cells plays an important role during tumor progression. In this pilot study we compared biological functions of polymorphonuclear granulocytes (PMN) from the peripheral blood of HNSCC patients and healthy subjects. PMN were simultaneously isolated from the peripheral blood of HNSCC patients and healthy donors for functional analysis (apoptosis, production of reactive oxygen species (ROS), cytokine release and immunophenotyping). PMN from HNSCC patients showed a significantly lower inducible production of ROS (P = 0.02) and reduced spontaneous apoptosis (P= 0.008) compared with PMN from healthy donors. Under standard culture conditions, there was no significant difference regarding the release of inflammatory cytokines between PMN from HNSCC patients and PMN from healthy donors. Confirming previous observations, serum concentrations of PMN-related cytokines were significantly higher in the peripheral blood of HNSCC patients than in that of controls. Importantly, immunophenotyping revealed an increased number of immature PMN in PMN fractions isolated from HNSCC patients. Peripheral blood PMN from HNSCC patients and healthy donors show distinct functional differences. The presence of increased numbers of immature stages of PMN in HNSCC patients may partly contribute to the changes observed. After recruitment to and infiltration of the tumor, PMN may be further modulated in the local tumor microenvironment. This pilot study justifies functional analyses of myeloid cells in larger cohorts of patients with HNSCC. PMID- 21978701 TI - Validation of a diagnostic score for the diagnosis of autoinflammatory diseases in adults. AB - Most autoinflammatory disorders typically come out in the pediatric population, although a limited number of patients may experience disease onset during adulthood. To date, a late disease onset has been described only in familial Mediterranean fever, caused by mutations in the MEFV gene, and in tumor necrosis factor receptor-associated periodic syndrome, caused by mutations in the TNFRSF1A gene. The relative rarity and lack of information on adult-onset autoinflammatory diseases make it likely that mutations will be found in an even smaller percentage of cases. With the aim of improving the genetic diagnosis in adults with suspected autoinflammatory disorders, we recently identified a set of variables related to the probability of detecting gene mutations in MEFV and TNFRSF1A and, in addition, we have also proposed a diagnostic score for identifying those patients at high risk of carrying mutations in these genes. In the present study we evaluated the preliminary score sensitivity and specificity on a wider number of patients in order to validate the goodness of fit of the model. Two hundred and nineteen consecutive patients with a clinical history of periodic fever attacks were screened for mutations in MEFV and TNFRSF1A genes; detailed information about family/personal history and clinical manifestations were also collected. For the validation of the score we considered data both from the 110 patients used to build the preliminary diagnostic score and from the additional 219 patients enrolled in the present study, for a total number of 329 patients. Early age at disease onset, positive family history for recurrent fever episodes, thoracic pain, abdominal pain and skin rash, which are the variables that had previously been shown to be significantly associated with a positive genetic test result (12), were used for validation. On univariate analysis the associations with a positive genetic test were: age at onset (odds ratio [OR] 0.43, p=0.003), positive family history for recurrent fever episodes (OR 5.81, p<0.001), thoracic pain (OR 3.17, p<0.001), abdominal pain (OR 3.80, p<0.001) and skin rash (OR 1.58, p=0.103). The diagnostic score was calculated using the linear combination of the estimated coefficients of the logistic multivariate model (cut-off equals to 0.24) revealing good sensitivity (0.778) and good specificity (0.718). In conclusion, our score may serve in the diagnostic evaluation of adult patients presenting with recurrent fever episodes suspected of having an autoinflammatory disorder, helping identify the few subjects among them who may be carriers of mutations in MEFV and TNFRSF1A genes. PMID- 21978702 TI - Combination treatment of flag with non-pegylated liposomal doxorubicin (MYOCET(TM)) in elderly patients with acute myeloid leukemia: a single center experience. AB - The incidence of acute myeloid leukemia (AML) increases with age, but results of intensive chemotherapy in elderly patients are disappointing. Non-pegylated liposomal formulations of doxorubicin (MyocetTM) have been developed with the aim of reducing systemic and cardiac toxicity especially in the elderly. We evaluated the efficacy and toxicity profiles of fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG) regimen given in association with MyocetTM in 35 patients with AML, median age 69 years (range 61-83 years). Nineteen (54.3%) had newly-diagnosed AML, twelve (34.3%) patients had secondary AML (ten with Myelodisplastic Syndrome, two with Primary Myelofibrosis) and 4 (11.4%) patients had had a late relapse (>12 months) of AML. Complete remission (CR) and partial remission (PR) were obtained in twenty-two (63%) and 3 (8.5%) patients, respectively. Seven (20%) patients showed a resistant disease. There were 3 early deaths (8.5%). Six patients (17%) experienced severe cardiovascular toxicity. The median overall survival (OS) was 12 months (range 1-52 months) with a median disease-free survival (DFS) of 20 months (range 1-48 months). One-year and two year DFS were 78.9% and 26.7%, respectively. This study demonstrates that in elderly patients with AML, FLAG-Myocet combination shows promising efficacy response with acceptable toxicity, enabling most patients to receive further treatments, including transplantation procedures. PMID- 21978703 TI - Metallosis following knee arthroplasty: a histological and immunohistochemical study. AB - Metallosis represents a rare and severe complication of knee replacement surgery. It is caused by the infiltration and accumulation of metallic debris into the peri-prosthetic structures, deriving from friction between metallic prosthetic components. In knee arthroplasty, this event generally occurs as a result of polyethylene wear of the tibial or metal-back patellar component. The real incidence of metallosis is still unknown, although it seems to be more frequent in hip than in knee arthroplasty. The metallic debris induces a massive release of cytokines from inflammatory cells, making a revision necessary whenever osteolysis and loosening of the prosthesis occur. We report four patients who underwent revision of their knee arthroplasty because of severe metallosis. In one of these patients, polyethylene wear had determined friction between the metal-back patellar component and the anterior portion of the femoral component. In the remaining three cases, metallosis was caused by friction between the femoral and tibial prosthetic metal surfaces, resulting from full-thickness wear of the tibial polyethylene. T lymphocytes were activated by metal particles present in periprosthetic membranes. In all patients, one-stage revision was necessary, with rapid pain disappearance and a complete functional recovery of the knee joint. PMID- 21978704 TI - Evolution of hypogammaglobulinemia in premature and full-term infants. AB - There are few data in the literature reporting the evolution of hypogammaglobulinemia in premature and full-term infants during the first years of life. The aim of this study was to assess the clinical and immunological evolution of premature and full-term infants with hypogammaglobulinemia. We included 24 children (11 premature and 13 full-term infants), aged 0-36 months, with hypogammaglobulinemia. Fifteen (62.5%) children had an isolated reduction in IgG, 7 (29.2%) had a decrease in both IgG and IgA and 2 (8.3%) a reduction in IgG and IgM. Normalization of IgG serum levels occurred in the premature infants at a mean age of 7.2 months. Full-term infants were divided into 3 groups based on age at normalization of IgG serum level: A) hypogammaglobulinemia with normalization within 12 months of life; B) with normalization within 36 months of life; C) normalization after 36 months. All the premature infants with hypogammaglobulinemia recovered, even though in the lower limits for age in the first years, while transient hypogammaglobulinemia observed in full-term infants has a different age of recovery. PMID- 21978705 TI - Long-term N-acetylcysteine therapy in systemic sclerosis interstitial lung disease: a retrospective study. AB - Systemic sclerosis (SSc) is associated with interstitial lung diseases. The primary endpoints of this study were changes between baseline and month 24 in single-breath carbon monoxide diffusing capacity (DLco). The secondary endpoints were: vital capacity (VC), forced expired volume in 1 sec (FEV1), total lung capacity (TLC), scores of high resolution computed tomography (HRCT) of the chest, number of adverse effects. In this study, we retrospectively investigated data from SSc patients who had undergone therapy with high-dose intravenous N acetylcysteine (NAC) at a dosage of 15 mg/Kg/h for 5 consecutive hours every 14 days. After NAC therapy median values of DLco (69.5 vs 77.7%), VC (99 vs 101.3%) and TLC (93 vs 98.3%) significantly increased. We did not observe any significant changes from baseline in FEV1 value and HRTC score. The improvement in lung function was more evident in SSc patients without radiological signs of pulmonary fibrosis than in patients with pulmonary fibrosis. In SSc patients with mild moderate pulmonary fibrosis intravenous NAC administration slows the rate of deterioration of DLco, VC and TLC. In conclusion, this retrospective study demonstrates that long-term therapy with intravenous NAC ameliorates pulmonary function tests in SSc patients. PMID- 21978706 TI - The protective role of catalase against cerebral ischemia in vitro and in vivo. AB - The present study aims to assess the protective role of the antioxidant enzyme catalase (CAT) with relation to hydrogen peroxide (H(2)O(2)) degradation in oxygen plus water on electrophysiological and fluorescence changes induced by in vitro ischemia and on brain damage produced by transient in vivo ischemia. Neuroprotective effects of CAT were determined by means of electrophysiological recordings and confocal fluorescence microscopy in the hippocampal slice preparation. Ischemia was simulated in vitro by oxygen/glucose deprivation (OGD). In vivo ischemia was produced by transient middle cerebral artery occlusion (MCAo). A protection of the rat CA1 field excitatory postsynaptic potential (fEPSP) loss caused by a prolonged OGD (40 min) was observed after exogenous CAT (500 U/mL) bath-applied before a combined exposure to OGD and H(2)O(2) (3 mM). Of note, neither H(2)O(2) nor exogenous CAT alone had a protective action when OGD lasted for 40 min. The CAT-induced neuroprotection was confirmed in a transgenic mouse model over-expressing human CAT [Tg(CAT)]. In the presence of H(2)O(2), the hippocampus of Tg(CAT) showed an increased resistance against OGD compared to that of wild-type (WT) animals. Moreover, CAT treatment reduced for about 50 min fEPSP depression evoked by repeated applications of H(2)O(2) in normoxia. A lower sensitivity to H(2)O(2)-induced depression of fEPSPs was also indicated by the rightward shift of concentration-response curve in Tg(CAT) compared to WT mice. Noteworthy, Tg(CAT) mice had a reduced infarct size after MCAo. Our data suggest new strategies to reduce neuronal damage produced by transient brain ischemia through the manipulation of CAT enzyme. PMID- 21978707 TI - The expression of TSLP receptor in chronic rhinosinusitis with and without nasal polyps. AB - Chronic Rhinosinusitis with or without Nasal Polyps (CRSwNP and CRSsNP) may be characterized by different cytokine profiles. Generally, Th2 cytokines and eosinophilic infiltration have been reported to be more specific of CRSwNP compared to CRSsNP, where neutrophils seem to play a major role. The epithelial cell-derived thymic stromal lymphopoietin (TSLP) has been recently identified as a key factor in Th2-inflammatory response. The aim of this study is to investigate the expression of TSLP Receptor (TSLP R) in surgical specimens obtained from patients affected by CRSwNP (n=10) and CRSsNP (n=5) by immunohistochemical techniques (immunostaining score, IS). TSLP R expression was significantly higher in the inflammatory infiltrate and in the epithelial cells of CRSwNP, CRSsNP patients compared to the control group (IS 4.5+/-0.68, 4.4+/ 1.44 and 0.43+/-0.3 respectively, p=0.0024 for inflammatory infiltrate and IS 5.8+/-0.92, 7.8+/-2.06 and 0.86+/-0.55 respectively, p=0.0018 for epithelial cells). No significant difference was observed in IS of inflammatory infiltrate and epithelial cells in CRSwNP compared to CRSsNP. Very low IS for TSLP R was found in connective tissue of all the samples, with no difference among the groups. TSLP receptor is highly expressed in CRS compared to controls and independently from the polyps suggesting an early common inflammatory pathway in the two CRS phenotypes. PMID- 21978708 TI - Urinary excretion of 5-hydroxy-3-indoleacetic acid in dystimic/depressed, adult obese women: what correlations to hepatic steatosis? AB - The synthesis of serotonin at CNS level is influenced by diet. Moreover, insulin resistance is associated with lower serotonin levels. Visceral obesity, strictly linked to hepatic steatosis is specifically associated with mild to severe somatic affective-depressive symptom clusters. Previous data support the view that depression involves serotonergic systems, reflecting low levels of urinary 5 hydroxy-3-indoleacetic acid (5-HIAA). The 24-h urinary excretion of 5-HIAA was evaluated in 76 dystimic/depressed, obese/overweight females, divided into two groups, i.e., on a hyper-caloric diet, associated with a life style characterized by leisure time sedentary behavior (LTSB, 35 women), or on a normo-caloric diet, assisted by program-based strategies aimed at promoting physical activity participation (PAP, 41 women). Beck Depression Inventory (BDI) was carried out to score the severity of dystimia/depression. Anthropometric measures, metabolic indices, severity of hepatic steatosis at sonography and HOMA were studied. Urinary levels of 5-HIAA in controls and PAP groups were comparable with a great overlap, while in the LTSB group the urinary excretion of 5-HIAA was significantly reduced in respect to that of the PAP group and obviously compared to that of the control group, 3.4+/-1.4 mg/L versus 6.2+/-2.7 mg/L and 6.4+/-2.6 mg/L, respectively, ANOVA test, P= 0.001. Among metabolic indices, cholesterol, HDL-cholesterol, triglycerides and uric acid were not able to predict urinary concentrations of 5-HIAA, which were not associated with hepatic steatosis; vice versa, ferritin levels, and mainly HOMA values, were independent predictors of the urinary excretion of 5-HIAA (beta=0.235 and 0.45, respectively). Dystimia/depression severity was negatively predicted by urinary 5-HIAA levels in the sense that the highest BDI values were forecast by the lowest values of urinary 5-HIAA (beta= -0.72).The importance of measuring the 24-h urinary excretion of 5-HIAA in follow-ups could rely on a method simultaneously mirroring the well-being status, the adherence to physical activity, which leads to improved insulin sensitivity, and the eating habits acquired by dystimic/depressed overweight/obese patients. In contrast, the significance of the urinary 5-HIAA is reduced in evaluating the severity of hepatic steatosis, likely because it is a structured process. PMID- 21978709 TI - Analysis of expression profile of gene encoding proteins of signal cascades activated by insulin-like growth factors in colorectal cancer. AB - The aim of the study is to analyse gene typing with the use of the microarray technique (HG-U133A, Affymetrix), differentiating colorectal cancer tissues from tissues assessed histopathologically as healthy ones among a panel of 93 mRNA of gene encoding proteins involved in the activation of cellular signal transduction pathways by insulin-like growth factors. The study was conducted on a group of 8 colorectal cancer patients. Frozen tumor and healthy specimens from the patients were used in molecular tests. Transcript IGF2 differentiated cancer from healthy tissue. Among the genes participating in the cascade of signal transfer in cells activated by IGF, GRB10, PIK3R3, PIK3R1, and IRS1 were qualified as differentiating transcripts. IRS1 indicated over-expression in tumour. Transcript SMAD2 showed a significant changed in tumour samples (increased expression). PMID- 21978710 TI - Reduced sebum production in Turner syndrome: a study of twenty-two patients. AB - Turner's syndrome (TS) is a genetic disorder caused by numeric and/or structural abnormalities of the X chromosome. In a previous study it was observed that acne is less frequent in TS than in the general population. Since the onset of acne in pre-pubertal or pubertal age is related to sebum production, this study evaluates sebum secretion in TS patients, comparing the results with those of a control group of age-matched healthy female subjects. A total of 22 patients affected by TS (mean age 26.56+/-7.89 years) and a control group of 23 age-matched healthy females were studied. Sebum production was measured using a Sebumeter SM810. Mean sebum secretion in TS subjects was significantly lower than in the control group (81.35+/-66.44 UA vs 147.09+/-33.62 UA, p<0.001) and this significant difference was found in every facial zone. The reduction of sebum secretion may explain, using a simple and non-invasive method, the absence or the low incidence of acne in TS patients. PMID- 21978711 TI - Antibacterial activity of methyl aminolevulinate photodynamic therapy in the treatment of a cutaneous ulcer. AB - We describe a 79-year-old female with a chronic venous ulceration infected by Staphylococcus aureus and Enterococcus faecalis and not responsive to conventional treatments. The patient was treated with Methyl-Aminolaevulinate Photodynamic Therapy (MAL-PDT). After four weeks the cutaneous swabs become negative and we observed a significant clinical improvement. Therefore we suppose that MALPDT could represent a valid therapeutic option in the treatment of infected chronic ulcers. PMID- 21978712 TI - Clinical and serological features of patients with suspected Lyme borreliosis. AB - Serology is currently the method of choice for the laboratory diagnosis of Lyme Borreliosis, but it must be interpreted with caution. A total of 954 patients with suspected Lyme borreliosis were evaluated on the basis of clinical and serological data. The seroprevalence of Borrelia burgdorferi antibodies was 4.4% (42 of the 954 serum samples). The most frequent clinical manifestation was erythema migrans which occurred in 50% of the seropositive patients, followed by neuroborreliosis (16.6%) and arthritis (11.9%). Carditis was rare. Our findings suggest that for the diagnosis of Lyme borreliosis, serologic tests need to be combined with clinical signs and symptoms. PMID- 21978713 TI - Oral desensitisation with food is food-specific and protein-specific. AB - The avoidance of food(s) is the main therapeutic approach to food allergy. Nevertheless, orally- or sublingually-administered food allergens have gained attention and a number of food-allergic children can tolerate gradually increasing amounts of cow's milk and hen's egg. Our purpose is to show that oral desensitisation with food is an allergen-specific therapeutic approach and for this, we describe 4 illustrative children with IgE-mediated food allergy. The first was allergic to cow's milk and hen's egg, the second to cow's milk, hen's egg and fish. Both underwent oral desensitisation to both cow's milk and hen's egg. The third child was allergic to cow's milk, hen's egg and fish and underwent oral desensitisation with cow's milk. The last child was allergic to raw but not to cooked/boiled hen's egg and underwent the oral desensitisation with hen's egg. The first 2 children reached the clinical tolerance to cow's milk after the cow's milk oral desensitisation, but reached the hen's egg tolerance only after the hen's egg oral desensitisation. Moreover, the second child did not tolerate fish after being desensitised to both cow's milk and hen's egg. The third child tolerated cow's milk, but not hen's egg and fish, at the end of the cow's milk oral desensitisation. The fourth child could tolerate the previously not tolerated raw hen's egg after the oral desensitisation with raw hen's egg. In conclusion, we indicate that oral desensitisation with food is allergen specific. The induction of the clinical tolerance to one food is not followed by the tolerance to the other food(s) that the patient is allergic to. To obtain a double or multiple food tolerance, separate desensitisation protocols, one for each food, have to be carried out. Oral desensitisation with food discriminates between raw and cooked proteins. PMID- 21978714 TI - Nares patients have more respiratory infections than allergic subjects. AB - Respiratory infections (RI) represent a frequent challenge for physicians. Allergic patients could present higher susceptibility to contract RI than non allergic subjects. Non-allergic rhinitis with eosinophils (NARES) has been little investigated. This preliminary study was performed to evaluate the number and duration of RI and their sequelae in NARES and allergic patients, and non allergic healthy subjects. Forty healthy non-allergic subjects (22 males, mean age 29 years), 40 patients with allergic rhinitis (AR) (19 males, mean age 35), and 40 NARES patients (18 males, mean age 34) were evaluated. The considered parameters were: nasal eosinophils, total number, duration in days of RI, and RI severity. NARES patients had more eosinophils than AR patients and normal controls (p<0.01); RI duration was longer in NARES patients than in AR ones (p<0.05) and controls (p<0.01); RI were more severe in NARES patients than in AR ones (p<0.05) and controls (p<0.01); pneumonia and asthma were more frequent in both NARES and AR patients than controls (p<0.05 and p<0.01). In conclusion, this preliminary study shows that NARES may induce more severe respiratory infections than allergic rhinitis. PMID- 21978715 TI - Nonclassical major histocompatibility complex I-like Fc neonatal receptor (FcRn) expression in neonatal human tissues. AB - The neonatal Fc receptor (FcRn) was demonstrated to play a role both in the recycling and thus the protection of immunoglobulin G (IgG) from catabolism and in the maternal-fetal transfer of IgG. The expression of this particular receptor was evidenced in a variety of cell types, but the endothelial cell was considered the main cell able to perform both recycling and IgG catabolism. Based on preliminary data obtained in adult human mammary glands and skin, this study focused on a number of neonatal human tissues, targeting FcRn expression mainly in epithelial versus endothelial cells. Our results demonstrate that in most of the investigated tissues, the neonatal Fc receptor is not detectable in the endothelial cells lining the capillaries, whereas most epithelial cells are positive. We could also observe the receptor's expression in most macrophages, smooth muscle cells, and neurons. Taken together, these data suggest that the main sites of IgG catabolism might in fact be other than endothelial cells in human neonates. PMID- 21978716 TI - Intraoperative cooling of iliac bone graft: an experimental evaluation of cell viability. AB - PURPOSE: A cancellous iliac bone graft is used to treat alveolar clefts. A few hours can exist between graft harvest and placement into the alveolar defect. The purpose of this study was to determine whether intraoperative cooling of bone optimizes viability and to evaluate cellular preservation of cooled graft over time. PATIENTS AND METHODS: Twelve cancellous iliac bone graft specimens were obtained prospectively from consecutive patients undergoing alveolar cleft repair. Each sample was collected during graft procurement and divided into 3 groups: group 1 (immediate analysis), group 2 (analysis after 2 hours at room temperature), and group 3 (analysis after 2 hours on ice). To generate a viability curve, iliac bone specimens were stored on ice and assayed immediately and hourly for 8 hours. Resazurin, an oxidation-reduction indicator of metabolically active cells, was used to assess cellular viability (normalized relative fluorescence units). RESULTS: Group 1 (n = 7,370) had more active cells than did group 2 (n = 4,104) or group 3 (n = 5,005; P = .03). Group 3 had greater viability than group 2 (P = .03). Cellular preservation of the cooled graft was 100% at the immediate analysis, 98.4% +/- 13.9% at 1 hour, 91.8% +/- 9.8% at 2 hours, 83.1% +/- 31.8% at 3 hours, 71.8% +/- 27.2% at 4 hours, 71.4% +/- 16.9% at 5 hours, 69.9% +/- 19.0% at 6 hours, 70.0% +/- 22.5% at 7 hours, and 66.7% +/- 13.3% at 8 hours. CONCLUSIONS: Storing iliac bone graft on ice rather than at room temperature optimizes cellular viability, with cooled bone demonstrating 22.0% more active cells after 2 hours. Cellular loss of cooled graft plateaued after 4 hours. Clinically, the iliac graft should be maintained on ice until placed into the alveolar cleft. PMID- 21978717 TI - Distraction osteogenesis combined with tissue-engineered cartilage in the reconstruction of condylar osteochondral defect. AB - PURPOSE: Surgical rehabilitation of condylar osteochondral defect remains a challenge for surgeons. The aim of this study was to explore the feasibility of combining distraction osteogenesis with tissue-engineered cartilage in the reconstruction of condylar osteochondral defect. MATERIALS AND METHODS: A condylar defect model was established in 18 goats that were randomly divided into 2 groups: the experimental group and the control group. Mandibular ramus osteotomies were performed and distractors were implanted in all animals. The mixture of chondrocytes and Pluronic F-127 (Sigma-Aldrich, St Louis, MO) was injected on the notched surface of a transport disc in the experimental group, whereas a scaffold without cells was transplanted into the control group. After a 5-day latency period, distraction was activated at a rate of 0.5 mm twice per day for 15 days. The goats were killed at the end of the fourth, eighth, or twelfth week in the consolidation period. Specimens were harvested and macroscopic evaluation, as well as Masson trichrome and immunohistochemical staining, were performed to compare the results between the 2 groups. RESULTS: Osteogenesis was found in all animals with no evidence of infection. Condyle-like structures were formed at the upper end of the transport segment in all animals. The neocondylar surface was covered with a layer of smooth lustrous fibrocartilage in the experimental group. Collagen was shown in the reparative tissue by Masson trichrome staining. Immunohistochemistry staining indicated that type II collagen was positive, whereas type I collagen was negative on the neocondylar surface in the experimental group. No cartilage-like tissue was seen, but fibrous tissue was identified at the bony surface in the control group. In the experimental group, immunofluorescent semiquantitative analysis showed that the positive rate of type II collagen was 1.62% +/- 0.53% after the fourth week of consolidation, and it increased to 12.39% +/- 3.27% after the twelfth week. There was a significant difference in the expression of type II collagen between the goats examined after the fourth week, and those examined after the twelfth week. CONCLUSION: The combination of distraction osteogenesis with tissue-engineered cartilage is an ideal alternative in the reconstruction of condylar osteochondral defect. By use of this method, the simultaneous rehabilitation and regeneration of condylar bone and cartilage were achieved. PMID- 21978718 TI - Bisphosphonate-related osteonecrosis of the mandible secondary to postural pressure. PMID- 21978719 TI - Maxillary metastasis of a medullary thyroid carcinoma in a 21-year-old woman 7 years after thyroidectomy. PMID- 21978720 TI - Immunoglobulin G4-related sclerosing inflammatory pseudotumors presenting in the oral cavity. PMID- 21978721 TI - Positive thinking in anxiety disordered children reconsidered. AB - Negatively valenced thoughts are assumed to play a central role in the development and maintenance of anxiety. However, the role of positive thoughts in anxiety is rather unclear. In the current study we examined the role of negative and positive self-statements in the anxiety level of anxious and non-anxious children. Participants were 139 anxiety disordered children and 293 non-anxious children (8-18 years). Compared to non-anxious children, anxious children reported more negative thoughts, less positive thoughts and lower State of Mind (SOM) ratios (ratio of positive to negative thoughts). Negative thoughts and SOM ratios were the strongest predictors of anxiety level in anxious children; whereas both negative and positive thoughts were the strongest predictors of anxiety level in non-anxious children. To conclude, a lack of positive thoughts might be more than just an epiphenomenon of anxiety level and might deserve a place in the cognitive model of anxiety. PMID- 21978722 TI - Low level of ventricular CSF orexin-A is not associated with objective sleepiness in PD. PMID- 21978723 TI - Sleep of preschool children with night-time fears. AB - BACKGROUND: Night-time fears are very common in preschool and early school years. However, to date, the links between night-time fears and sleep have not been assessed systematically. The aim of this study was to evaluate natural sleep patterns in children with night-time fears, and to assess the association between parental fear-related strategies and children's sleep disruptions. METHODS: Sleep was assessed in a sample of 109 preschool children (64 boys and 45 girls) aged 4 6 years suffering from significant night-time fears, and in 30 healthy controls using actigraphy and parental reports. RESULTS: Controls slept significantly better than the children with night-time fears. The disrupted sleep patterns of the children with night-time fears were reflected in a higher number of actigraphic night wakings, shorter periods of continuous sleep, shorter true sleep time, and a lower percentage of actual sleep time. Similar findings were manifested in sleep measures reported by the parents. Parental fear-management strategies were found to be linked to impaired actigraphic sleep measurements. CONCLUSIONS: Children with night-time fears are at risk for developing poor sleep quality, which may further compromise their psychological well-being. PMID- 21978724 TI - Depressive symptoms and obesity as predictors of sleepiness and quality of life in patients with REM-related obstructive sleep apnea: cross-sectional analysis of a large clinical population. AB - BACKGROUND: The clinical significance of rapid eye-movement (REM)-related obstructive sleep apnea (OSA) is unknown. Moreover, it is unclear what the determinants of sleepiness and quality of life (QoL) are among these patients. Our aim was to identify whether the apnea-hypopnea index during REM sleep (AHI(REM)), AHI during NREM sleep (AHI(NREM)), depressive symptoms, or obesity are independent predictors of excessive daytime sleepiness and reduced QoL in patients with REM-related OSA. We also assessed if these characteristics were predictors of sleepiness and QoL in all patients with OSA (AHI >= 5) as well as in non-stage specific OSA. METHODS: This was a cross-sectional analysis of a clinic-based population with OSA. In order to minimize the contribution of AHI(NREM), we defined REM-related OSA using the following criteria: an overall AHI >= 5, AHI(REM)/AHI(NREM) >= 2, AHI(NREM) the lowest quartile of the entire cohort. We examined the predictors of subjective sleepiness using the Epworth Sleepiness Scale (ESS) and QoL using the short-form quality of life questionnaire-12 (SF-12). RESULTS: Of 1019 consecutive adults that were referred for their first in-laboratory polysomnogram for suspicion of OSA over a 10 month period, 931 had OSA. REM-related OSA was present in 126 patients. In adjusted linear regression models, AHI(NREM) was a significant predictor of sleepiness in the entire cohort of patients with OSA as well as non-stage specific OSA, but not in the REM-related OSA group. AHI(REM) was not a significant predictor of ESS or QoL in any of the three groups. However, greater depressive symptoms and body mass index were significant independent predictors of ESS and reduced QoL in the REM-related OSA group. CONCLUSION: Higher depression scores and obesity, rather than the severity of OSA (as measured by AHI(NREM) and AHI(REM)), were predictive of sleepiness and QoL scores in patients with REM-related OSA. PMID- 21978725 TI - Screening for obstructive sleep apnea in early outpatient cardiac rehabilitation: feasibility and results. AB - BACKGROUND: Obstructive sleep apnea (OSA) has been recognized as a risk factor for cardiovascular disease and mortality. The aim of this study was to determine the feasibility and efficacy of implementing a screening program for OSA in early outpatient cardiac rehabilitation (CR) and to estimate the risk for OSA in this population. METHODS: From 535 consecutive patients enrolled in early outpatient CR we screened 383 (72%) patients and classified them as low- vs. high-risk for OSA using the Berlin questionnaire. Those considered at high-risk for OSA were referred for further evaluation. We assessed the yield and feasibility of the screening program, patient compliance with referral, and the percentage of patients diagnosed with OSA after polysomnography. RESULTS: Mean age was 63 +/- 12 years, 70% were men, 20% had diabetes, 65% had hypertension, and 58% had experienced a recent myocardial infarction. Two hundred and one patients (52%) had a high risk for OSA based on the questionnaire. Of the 169 who completed the CR program, only 111 (78%) were referred for further evaluation (Fig. 1). Of the 74 patients who completed their OSA work-up, 39 were found to have OSA with an apnea-hypopnea index of >= 5 events/h. CONCLUSIONS: Implementation of a simple screening program for OSA in early outpatient CR is feasible with minimal incremental resources. A significant percentage of patients at high-risk decline further evaluation, suggesting that their perceived risk for OSA and its consequences may be low. PMID- 21978726 TI - Clinical efficacy and safety of IV ferric carboxymaltose (FCM) treatment of RLS: a multi-centred, placebo-controlled preliminary clinical trial. AB - OBJECTIVE: Intravenous (IV) iron has been used as a treatment to reduce Restless Legs Syndrome (RLS) symptoms, but two double-blinded trials of a frequently prescribed IV iron formulation, iron sucrose, failed to show lasting efficacy. This study evaluates efficacy and safety of a new IV iron formulation (ferric carboxymaltose, FCM) with molecular properties that may make iron more available for uptake to the brain than iron sucrose does. METHODS: In this 28-day, multi centre, randomised, placebo-controlled trial 46 RLS patients were discontinued from all RLS treatment. Twenty-four received 500 mg FCM in two doses 5 days apart and 22 received a matching placebo. At day 28, those on placebo were given a single 1000 mg IV FCM and those not responding to initial treatment were given a third dose of 500 mg FCM. Patients were followed up for 24 weeks or until needing added RLS treatment. RESULTS: FCM significantly improved primary and secondary outcomes compared to placebo: International Restless Legs Syndrome study group severity scale (IRLS) average (SD) decrease of 8.9 (8.52) versus 4.0 (6.11), p=0.040; Clinical Global Inventory of Change (CGI-1) very much or much improved 48.3% versus 14.3%, p=0.004. Quality of life was also significantly improved. Of the 24 with initial iron treatment 45% responded and 29% remitted (IRLS <= 10) at day 28, and 25% continued free of other RLS medications at 24 weeks after treatment. The single 1000 mg dose on day 28 produced the same degree of treatment response as the divided dose, but the added 500 mg dose for those not responding to the initial treatment showed little benefit. There were no significant adverse events. CONCLUSIONS: IV FCM provided a safe and effective treatment for RLS that lasted for at least 24 weeks for some patients. Larger studies are needed to confirm these results. PMID- 21978727 TI - Cross-reactivity with endogenous proBNP from heart failure patients for three commercial BNP immunoassays. PMID- 21978728 TI - Elevated CSF levels of TACE activity and soluble TNF receptors in subjects with mild cognitive impairment and patients with Alzheimer's disease. AB - We recently reported that expression levels of tumor necrosis factor (TNF) receptors, TNFR1 and TNFR2, are significantly changed in the brains and cerebrospinal fluid (CSF) with Alzheimer's disease (AD). Moreover, we also found that, in an Alzheimer's mouse model, genetic deletion of TNF receptor (TNFR1) reduces amyloid plaques and amyloid beta peptides (Abeta) production through beta secretase (BACE1) regulation. TNF-alpha converting enzyme (TACE/ADAM-17) does not only cleave pro- TNF-alpha but also TNF receptors, however, whether the TACE activity was changed in the CSF was not clear. In this study, we examined TACE in the CSF in 32 AD patients and 27 age-matched healthy controls (HCs). Interestingly, we found that TACE activity was significantly elevated in the CSF from AD patients compared with HCs. Furthermore, we also assayed the CSF levels of TACE cleaved soluble forms of TNFR1 and TNFR2 in the same patients. We found that AD patients had higher levels of both TACE cleaved soluble TNFR1 (sTNFR1) and TNFR2 (sTNFR2) in the CSF compared to age- and gender-matched healthy controls. Levels of sTNFR1 correlated strongly with the levels of sTNFR2 (rs = 0.567-0.663, p < 0.01). The levels of both sTNFR1 and sTNFR2 significantly correlated with the TACE activity (rs = 0.491-0.557, p < 0.05). To examine if changes in TACE activity and in levels of cleaved soluble TNFRs are an early event in the course of AD, we measured these molecules in the CSF from 47 subjects with mild cognitive impairment (MCI), which is considered as a preclinical stage of AD. Unexpectedly, we found significantly higher levels of TACE activity and soluble TNFRs in the MCI group than that in AD patients. These results suggest that TACE activity and soluble TNF receptors may be potential diagnostic candidate biomarkers in AD and MCI. PMID- 21978729 TI - The reverse superficial temporal artery flap from the preauricular region, for the small facial defects. AB - BACKGROUND: For the reconstruction of facial defects, the retroauricular flap is generally used. However, this flap has disadvantages, such as venous return disturbance and reddish skin colour peculiar to the retroauricular region. METHODS: Here, we report the reverse superficial temporal artery (STA) flap, elevated from the preauricular region. In our method, the flap is retrogradely elevated including the STA under the skin island in the preauricular region and the temporoparietal fascia around the superficial temporal vessels in the temporal region. The donor site is closed primarily or by the retroauricular flap. RESULTS: Five cases with a pedicled flap and one case with a free flap were treated using our method. In one case, a minor congestion of the flap occurred postoperatively, and temporary facial nerve palsy in another case. In all cases, the results were cosmetically good, and the scar at the donor site was inconspicuous. CONCLUSIONS: As compared to the retroauricular flap, our method is easier to perform and the flap has a reliable blood circulation. Moreover, it can be used with both a pedicled and a free flap, leaving an inconspicuous scar at the donor site, and a colour match without reddish skin. Therefore, when considering reconstruction of small-sized defects on the face, our method is more useful than the retroauricular flap. PMID- 21978730 TI - Combined autologous free dermis graft and lipofilling for correction of post traumatic upper lip notching. PMID- 21978731 TI - Speech outcomes in 10-year-old children with complete unilateral cleft lip and palate after one-stage lip and palate repair in the first year of life. AB - An evaluation of the results of one-stage repair of unilateral cleft lip and palate (UCLP) performed at the Institute of Mother and Child, Warsaw, Poland, has shown that the dentofacial outcomes are comparable with those of the best cleft centres. The aim of this study was to assess speech development after one-stage closure of UCLP. Twenty boys and eight girls at the mean age 9.6 years consecutively treated with one-stage closure of the cleft at the mean age of 8.8 (range, 6-13) months were included. The same surgeon performed palatal repair using a vomerplasty. The evaluated outcomes included (1) perceptual speech evaluations with assessment of hypernasality, audible nasal emissions (ANEs) and compensatory articulations, (2) evaluation of compensatory facial grimacing, (3) clinical intraoral evaluation and (4) videonasendoscopy when indicated. Our results demonstrated that 25 patients (89.3%) had normal nasal resonance. Severe hypernasality and compensatory articulation disorders caused by velopharyngeal insufficiency were assessed in one patient. In 13 patients (46.4%), oronasal fistulas were found. Two children (7%) with larger fistulas presented with mild hypernasality. In 11 cases (39.2%), fistula friction was heard at pronunciation of some anterior sounds. Ten children (35.7%) demonstrated compensatory facial grimacing, mostly inconsistent and mild, in the form of nasal valving. In conclusion, articulation development, velopharyngeal sphincter competence and incidence of compensatory articulations in our sample are satisfactory. However, only 54% of the present groups were rated as having entirely normal speech because of high incidences of anterior palatal fistulas, and mild but frequent fistula-related speech disturbances. PMID- 21978732 TI - Tailoring photonic metamaterial resonances for thermal radiation. AB - Selective solar absorbers generally have limited effectiveness in unconcentrated sunlight, because of reradiation losses over a broad range of wavelengths and angles. However, metamaterials offer the potential to limit radiation exchange to a proscribed range of angles and wavelengths, which has the potential to dramatically boost performance. After globally optimizing one particular class of such designs, we find thermal transfer efficiencies of 78% at temperatures over 1,000 degrees C, with overall system energy conversion efficiencies of 37%, exceeding the Shockley-Quiesser efficiency limit of 31% for photovoltaic conversion under unconcentrated sunlight. This represents a 250% increase in efficiency and 94% decrease in selective emitter area compared to a standard, angular-insensitive selective absorber.PACS: 42.70.Qs; 81.05.Xj; 78.67.Pt; 42.79.Ek. PMID- 21978733 TI - The g.-469G>A polymorphism in the GPIHBP1 gene promoter is associated with hypertriglyceridemia and has an additive effect on the risk conferred by LPL defective alleles. AB - BACKGROUND AND AIMS: Hypertriglyceridemia (hyperTG) is a component of the metabolic syndrome and a cardiovascular or pancreatitis risk factor. Although both genetic and environmental factors influence its expression, the biological component of hyperTG is still underestimated and has been reported in 10-20% of cases only. Given its key role in the lipolysis of TG-rich lipoproteins, glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) is a biological candidate for hyperTG. The aim of this study was to assess the association of new GPIHBP1 gene variants with hyperTG (fasting plasma TG values >= 2.0 mmol/L). METHODS AND RESULTS: Sequencing the GPIHBP1 gene identified a g.-469G > A (rs72691625) polymorphism in the promoter. A sample of 541 Caucasians (263 normoTG and 278 hyperTG) was then screened for this polymorphism using a 5'nuclease TaqMan. In multivariate analyses, GPIHBP1 g.-469G > A polymorphism carriers were at significantly higher risk of hyperTG (>= 2.0 mmol/L) than non-carriers, the odds ratio (OR) being 1.67 (p = 0.025) among heterozygotes and 5.70 (p = 0.004) in homozygotes. The simultaneous presence of loss-of-function LPL polymorphisms had an incremental additive effect on the risk of hyperTG (OR: 7.30; p < 0.001), highlighting the importance of gene-gene interactions in the expression of hyperTG. CONCLUSIONS: In this study, the g. 469G >A polymorphism in the GPIHBP1 gene promoter was associated with an increased risk of hyperTG and had an additive effect on the risk conferred by LPL defective alleles. PMID- 21978734 TI - The Affective and Emotional Composite Temperament (AFECT) model and scale: a system-based integrative approach. AB - Based on many temperament frameworks, here we propose an integration of emotional and affective temperaments (the AFECT model), forming a common substrate for mood, behavior, personality and part of cognition. Temperament is conceived as a self-regulated system with six emotional dimensions: volition, anger, inhibition, sensitivity, coping and control. The different combinations of these emotional dimensions result in 12 affective temperament types, namely depressive, anxious, apathetic, obsessive, cyclothymic, dysphoric, irritable, volatile, disinhibited, hyperthymic and euphoric. We also developed and validated a self-report scale to evaluate this construct, the Affective and Emotional Composite Temperament Scale (AFECTS). METHODS: Exploratory and confirmatory psychometric analyses were performed with the internet version of the AFECTS in 2947 subjects (72% females, 35+/-11years old). RESULTS: The factors interpreted as volition, anger, inhibition, sensitivity, coping and control showed very good Cronbach's alphas for 5 dimensions (0.87-0.90) and acceptable alpha for inhibition (0.75). Confirmatory factor analysis corroborated this 6-factor structure when considering inhibition as a second-order factor with fear and caution as first order factors (SRMR=0.061; RMSEA=0.053). In the Affective section, all 12 categorical affective temperaments were selected in the categorical choice, with 99% of volunteers identifying at least one adequate description of their affective temperament. LIMITATIONS: Only the internet version was used in a general population sample. CONCLUSION: The AFECT model provides an integrated framework of temperament as a self-regulated system, with implications for mental health, psychiatric disorders and their treatment. The AFECTS showed good psychometric properties to further study this model. PMID- 21978735 TI - The promoter of the serotonin transporter genotype, environment and depression: a hypothesis supported? PMID- 21978736 TI - Cholecystokinin system genes: associations with panic and other psychiatric disorders. AB - BACKGROUND: The cholecystokinin (CCK) system has long been hypothesised to have a role in the pathogenesis of panic attacks. Previous research into genetic variation within the CCK gene and the genes for its two receptors, CCKAR and CCKBR, has produced mixed results. We aimed to clarify this association by investigating multiple variants within each gene and multiple phenotypes associated with panic that may have confounded the previous studies' findings. METHODS: Variants were selected for the three genes based on HapMap CEU data. Individuals from a family based cohort (n=563) were genotyped for these variations and this data was analysed in FBAT. RESULTS: CCKBR showed the strongest association with panic, having multiple variants with p<0.05 (lowest: p=0.007). In CCKAR, some evidence was found for an association with panic, though further analysis suggested that the co-morbid bipolar-panic phenotype was most strongly associated. No variants in CCK were associated with panic but broader anxiety phenotypes did show associations. LIMITATIONS: Small sample size prevented thorough investigation of phenotypes, particularly pure disorders, and no correction was made for the multiple phenotypes analysed. CONCLUSIONS: Our findings support the involvement of variation in the CCK system, particularly CCKBR, in the pathogenesis of panic. Our data suggest that variation in CCK may be involved in several anxiety phenotypes and CCKAR may be involved in the development of panic co-morbid with bipolar disorder. These latter findings require further investigation and highlight the importance of clearly defined phenotypes when investigating psychiatric genetics. PMID- 21978737 TI - The impact of sexually abstaining groups on persistence of sexually transmitted infections in populations with ephemeral pair bonds. AB - Individuals often stop reproducing some time before they die. In this paper we compose and analyze a logistic two-sex population model in which individuals form pairs just to mate (i.e. pair bonds are ephemeral) and later move on to sexually abstaining groups. Using this model, we study the impact of sexually abstaining groups on persistence of a benign sexually transmitted infection (STI) in populations with such ephemeral pair bonds. We observe that the presence of sexually abstaining groups cannot prevent an STI from invasion or eliminate it when already present if the transition rates to the sexually abstaining groups are independent of the infection status of individuals (susceptible or infected). On the other hand, if they depend on that status, the presence of sexually abstaining groups can prevent an STI from invasion or eliminate it when present. Specifically, in the simple case of sex-independent vital parameters, this happens if the transition rate of the infected individuals to the sexually abstaining group is higher than the transition rate of the susceptible ones. These results contrast the earlier results based on assuming long-term, stable pair bonds, in which case one is capable of preventing or eliminating the disease with the same isolation rate for the susceptible and infected individuals. PMID- 21978738 TI - Functional contributions of astrocytes in synchronization of a neuronal network model. AB - In the present study, a biologically plausible neuronal population model is developed, which considers functional outcome of neuron-astrocyte interactions. Based on established neurophysiologic findings, astrocytes dynamically regulate the synaptic transmission of neuronal networks. The employed structure is based on the main physiological and anatomical features of the CA1 subfield of the hippocampus. Utilizing our model, we demonstrate that healthy astrocytes provide appropriate feedback control in regulating neural activity. In this way, the astrocytes compensate the increase of excitation coupling strength among neurons and stabilize the normal level of synchronized behavior. Next, malfunction of astrocytes in the regulatory feedback loop is investigated. In this way, pathologic astrocytes are no longer able to regulate and/or compensate the excessive increase of the excitation level. Consequently, disruption of astrocyte signaling initiates hypersynchronous firing of neurons. Our results suggest that diminishing of neuron-astrocyte cross-talk leads to an abnormal synchronized neuronal firing, which suggests that astrocytes could be a proximal target for the treatment of related disorders including epilepsy. PMID- 21978739 TI - Father figures. PMID- 21978740 TI - The prevalence of pyrethroid resistance phenotype and genotype in Rhipicephalus (Boophilus) microplus in Yucatan, Mexico. AB - A field survey was conducted to evaluate susceptibility of Rhipicephalus (Boophilus) microplus to cypermethrin on 49 farms in three areas of Yucatan, Mexico. The modified larval packet test was used to evaluate larval mortality at different cypermethrin concentrations. Dose-mortality regressions, lethal concentrations (LC(50)-LC(99)), confidence intervals and slope were estimated by probit analysis. Phenotype was defined as susceptible, tolerant or resistant when the resistance factor (RF) derived from both LC(50) and LC(99) determinations were <3, 3-5 or >5, respectively. An allele specific PCR (AS-PCR) was used to determine the frequency of a sodium channel mutation (F1550I, Phe->Ile) associated with pyrethroid resistance. Overall, 26.5%, 40.8% and 32.6% of tick populations were susceptible, tolerant and resistant to cypermethrin, respectively. A substantial inter-population variation in the level of cypermethrin response was evident (resistance factors ranged from 0.3 to 2599 and from 0.7 to >5000 when were indicated by the LC(50) and LC(99), respectively). The F1550I mutation (R allele) in R. microplus was present in all studied areas. The increasing presence of the R allele correlated well with increased levels of response indicated by both the LC(50) (r(2)=0.659, p=0.001) and LC(99) (r(2)=0.688, p=0.001) to cypermethrin. These results indicated that the F1550I mutation is a major common mechanism responsible for pyrethroid resistance in field populations of R. microplus ticks in the Mexican tropics. Both bioassay and AS-PCR showed that the prevalence of cypermethrin-resistant/tolerant R. microplus is high in Yucatan, Mexico and the relationship between the RF and the frequency of the R allele supports the role of F1550I as one of the most important mechanisms conferring pyrethroid resistance in these R. microplus populations. PMID- 21978741 TI - ParaCalc(r)--a novel tool to evaluate the economic importance of worm infections on the dairy farm. AB - Subclinical infections with gastrointestinal nematodes and liver fluke are important causes of production losses in grazing cattle. Although there is an extensive compilation of literature describing the effect of these infections on animal performance, only a few attempts have been made to convert these production losses to an economic cost. Here, we propose a novel tool (ParaCalc((r))), available as a web-application, to provide herd-specific estimates of the costs of these infections on dairy farms. ParaCalc((r)) is a deterministic spread-sheet model where results from diagnostic methods to monitor the helminth infection status on a herd and anthelmintic usage are used as input parameters. Default values are provided to describe the effects of the infections on production and the cost of these production losses, but the latter can be adapted to improve the herd-specificity of the cost estimate. After development, ParaCalc((r)) was applied on input parameters that were available for 93 Belgian dairy herds. In addition, the tool was provided to 6 veterinarians and their user experiences were evaluated. The estimated median [25th-75th percentile] cost per year per cow was ? 46 [29-58] and ? 6 [0-19] for gastrointestinal nematode and liver fluke infection, respectively. For both infections, the major components in the total costs were those associated with milk production losses in the adult cows. The veterinarians evaluated ParaCalc((r)) as a useful tool to raise the farmers' awareness on the costs of worm infections, providing added value for their services. However, the score given for user-friendliness was diverse among users. Although the model behind ParaCalc((r)) is a strong simplification of the real herd processes inducing economic losses, the tool may be used in the future to support economic decisions on helminth control. PMID- 21978742 TI - Applicability of in vitro bioassays for the diagnosis of ivermectin resistance in Rhipicephalus microplus (Acari: Ixodidae). AB - The applicability of laboratory bioassays to diagnose ivermectin (IVM) resistance in Rhipicephalus microplus was evaluated. Adult immersion tests (AITs), larval immersion tests (LITs) and larval packet tests (LPTs) were performed to characterise the effects of ivermectin toxicity on adults and larvae of a susceptible reference strain. The AIT was determined to be a reasonable assay but requires a large number of individuals to attain interpretable results. The LIT and LPT were validated with an IVM resistant strain, revealing resistance ratios (RRs) of 6.73 and 1.49, respectively. In a field survey, nine different populations of cattle tick from the states of Sao Paulo and Mato Grosso do Sul, Brazil, were analysed with the LIT. Populations without previous exposure to ivermectin exhibited RRs between 0.87 and 1.01. Populations previously exposed to IVM showed RRs between 1.83 and 4.62. The LIT was more effective at discriminating between resistant and susceptible populations than the LPT. The use of the LIT is recommended for the diagnosis of ivermectin resistance in R. microplus. PMID- 21978743 TI - Detection of polymorphism in AgB1 gene from sheep, cattle and human isolates of echinococcus granulosus by SSCP. AB - Antigen B (AgB) is a major protein produced by the metacestode cyst of Echinococcus granulosus, the causative agent of cystic hydatid disease. E. granulosus AgB is a gene family of at least five gene loci (B1-B5), each one consisting of several minor variants. We used PCR-SSCP followed by DNA sequencing to evaluate sequence variation and polymorphism of AgB1 in 99 isolates which the 43 were from cattle, 25 of sheep and 31 of human. All samples were analyzed with 12S rRNA-PCR for the strain detection and all of were identified as G1-G3 cluster (E. granulosus sensu stricto). The 16 human, 35 cattle and 25 sheep isolates were yielded the 102 bp band by PCR and these samples were tested by SSCP. As results of the SSCP, different band profiles were detected one each of cattle and human isolates while the other 74 isolates showed same band patterns. The DNA sequence analysis was performed for these two isolates and the other selected 4 isolates and polymorphism was confirmed. PMID- 21978744 TI - Evidence for bovine besnoitiosis being endemic in Italy--first in vitro isolation of Besnoitia besnoiti from cattle born in Italy. AB - Until 2009, bovine besnoitiosis had never been considered endemic in Italy and the only report on the disease in this country referred to animals imported from France shortly before. However, recently, an autochthonous outbreak of bovine besnoitiosis was reported in four herds located at the intersection of the borders between Emilia-Romagna, Toscana and Marche (Northern Apennine Mountains), which has led to an increased awareness concerning this disease. The present study describes a further outbreak of bovine besnoitiosis in Italy. The afflicted herd was a dairy herd with no evidence for contact with cattle from regions known to be endemic for bovine besnoitiosis. The farm investigation was initiated after a three-year old Holstein Friesian dairy cow with generalized thickening and lichenification of the skin was diagnosed with bovine besnoitiosis. The clinical diagnosis was confirmed by gross pathology, histopathology, serology and PCR. Bradyzoites released from tissue cysts obtained from the skin of this animal enabled the first in vitro isolation of Besnoitia besnoiti in Italy. This isolate was named Bb-Italy1. Sequencing of a 2118 bp spanning region including the complete internal transcribed spacer 1 and parts of the 18S and the 5.8S rRNA gene from DNA extracted from skin-derived zoites revealed a 99.9% identity to sequences known for other B. besnoiti isolated from cattle in Europe. Two GKO mice which had been inoculated intraperitoneally with bovine skin-derived bradyzoites became ill 7 days post inoculation. Parasitophorous vacuoles with multiplying zoites were observed in the cell culture inoculated with peritoneal fluids of these mice and a B. besnoiti infection in the mice and in the cell culture could be confirmed by real-time PCR. A serological investigation in the afflicted herd using immunoblots and an immunofluorescent antibody test (IFAT) revealed an overall herd seroprevalence of 9.7% (31/321), whereas within the female animals older than 2 years 17.0% (29/171) of the dams were tested positive. With one exception, an imported cow from Germany, all the seropositive animals were born in Italy. In connection with previously described autochthonous cases of bovine besnoitiosis the case described herein suggests that bovine besnoitiosis should be considered endemic in Italy. PMID- 21978745 TI - [Paleoendoscopy: the paleopathological study of Sancho's mummy, son of king Pedro I of Castilla The Cruel (xiv century)]. PMID- 21978746 TI - Factors associated with readmission after laparoscopic gastric bypass surgery. AB - BACKGROUND: Studies have demonstrated that laparoscopic Roux-en-Y gastric bypass (RYGB) is associated with the greatest readmission rate among bariatric surgeries. Some readmissions might be avoidable. We sought to evaluate the risk factors for readmission in a high-volume bariatric surgery program at a university hospital in the United States. METHODS: We performed a retrospective review of prospectively maintained data. Patients readmitted within 30 days of laparoscopic RYGB were randomly matched to control patients who had undergone RYGB in the same year but were not readmitted. The readmissions were categorized as technical complications (leak), wound infections, or malaise (nausea, dehydration, or benign abdominal pain). Patients with a wound infection treated in an outpatient setting were also evaluated and compared with the patients admitted with a wound infection. RESULTS: From July 2002 to July 2008, 450 patients underwent RYGB. Readmission occurred in 42 patients (9%). Of these 42 patients, 6 were admitted with wound infections (14%), 18 (43%) with malaise, and 18 (43%) with technical complications. The patients admitted with wound infections were similar to their controls, except that they were more likely to have publicly funded insurance (Medicare or Medicaid) and more likely to present for medical attention to the emergency department after clinic hours. The patients admitted with malaise reported a greater pain score at discharge and were also more likely to have public health insurance than controls. The patients with technical complications did not differ from the control patients in any examined variable. CONCLUSIONS: Patients with publicly funded insurance are at increased risk of readmission after RYGB. Outpatient mechanisms for managing wound infections and malaise might result in decreased readmissions. PMID- 21978747 TI - Clinical and instrumental evaluation of pelvic floor disorders before and after bariatric surgery in obese women. AB - BACKGROUND: Obesity, well known as a risk factor for several diseases, can also lead to pelvic floor dysfunction (PFD). However, scant data are available regarding PFD in obese individuals. Our study was designed to assess the prevalence, severity, and the quality of life (QOL) effect of PFD in obese women before and after bariatric surgery at a university hospital in Italy. METHODS: A total of 100 obese (body mass index [BMI] >=30 kg/m(2)) women completed 6 validated specific and QOL questionnaires about PFD. The patients were evaluated by physical examination, endoanal ultrasonography, rectal balloon distension test, and dynamic magnetic resonance imaging. Of the 100 patients, 87 were reassessed 12 months after bariatric surgery. RESULTS: The prevalence of PFD was 81%, and 49% of patients reported that their symptoms adversely affected their QOL. Urinary incontinence (UI) was the most common disorder (61%) and was associated with the BMI (P = .04). Fecal incontinence and pelvic organ prolapse symptoms were reported by 24 and 56 patients, respectively. Urogenital prolapse and rectocele was documented in 15% and 74% of patients, respectively. After a mean BMI reduction of 10 kg/m(2), the prevalence of PFD decreased to 48% (P = .02), with a significant improvement in QOL. The prevalence of UI decreased to 9.2% (P = .0001) and was associated with the decrease in postoperative BMI (P = .04). The rate of resolution of the symptoms was 84%, 85%, and 74% for UI, fecal incontinence, and pelvic organ prolapse, respectively. CONCLUSION: In the present sample of obese women, PFD was common and adversely affected their QOL. A clear association was found between the BMI and UI. Weight loss resulted in improved UI, fecal incontinence, and symptoms of pelvic organ prolapse. PMID- 21978748 TI - Effect of preoperative weight loss in bariatric surgical patients: a systematic review. AB - BACKGROUND: The potential benefit of preoperative weight loss in patients undergoing bariatric surgery has led many bariatric surgeons to recommend an aggressive weight reduction regimen to their patients. Some surgeons might withhold bariatric procedures if a certain threshold of preoperative weight loss is not achieved. It is unclear whether this practice has any scientific evidence supporting it. Our study aimed to examine the current evidence surrounding this issue in a systematic review. The setting was a university hospital. METHODS: A systematic search of multiple databases, including MEDLINE, Google Scholar, EMBASE, the Cochrane Library, and conference proceedings were reviewed, yielding a final total of 27 studies. Of the 27 studies, 7 were prospective studies (2 randomized controlled trials from the same patient population), 14 were retrospective studies (2 chart reviews from the same patient population), 1 was an editorial, and a number were conference presentations. RESULTS: A total of 17 trials, including approximately 4611 patients, deemed preoperative weight loss beneficial, and 10 studies, including 2075 patients, deemed preoperative weight loss to be of no benefit. The operative time was 12.5 minutes shorter for the preoperative weight loss patients undergoing laparoscopic Roux-en-Y gastric bypass. With regard to the effects of preoperative weight loss on postoperative weight loss, 9 studies (39%) reported a positive correlation, and 15 (62.5%) reported no benefit. Nine studies reporting perioperative complications (852 patients) revealed no difference in the complication rates, and 2 studies (1234 patients) suggested a significant decrease was associated with preoperative weight loss. CONCLUSION: This systematic review suggests little evidence is available to support or refute the routine use of preoperative weight reduction in bariatric surgery. Clearly, a large-scale, multicenter, randomized, controlled trial with sufficient power is necessary to clarify this significant aspect of preoperative care. PMID- 21978749 TI - Predictors of satisfaction with excess skin and desire for body contouring after bariatric surgery. AB - BACKGROUND: Bariatric surgery (BS) produces rapid, massive weight loss, often leaving patients with excess skin that can be esthetically disappointing and can present barriers to physical and psychosocial functioning. Thus, body contouring surgery (BCS) is frequently sought by post-BS patients. The objectives of the present study were to characterize the frequency at which post-BS patients desire BCS and the extent to which patients are satisfied with the excess skin in specific body regions before and after contouring. Furthermore, the present study sought to identify the predictors of which patients might be most desirous of BCS. This was a study conducted at 2 academic research centers. METHODS: Patients approximately 2 years or 6-10 years after BS were recruited and completed the Post-Bariatric Surgery Appearance Questionnaire. RESULTS: The participants expressed the greatest dissatisfaction with the skin at the waist/abdomen and thigh regions. The most commonly contoured site was the waist/abdomen, and patients rated greater satisfaction with this body region after BCS. Few significant predictor variables were identified. A greater BMI at survey completion was independently associated with lower satisfaction with excess skin, and the time elapsed since BS predicted the desire for contouring. CONCLUSION: These findings underscore the importance of educating BS candidates about the issues with redundant skin after weight loss and the possible need for subsequent BCS. With this education, patients might have more realistic expectations concerning BS outcomes and be better positioned to seek BCS when indicated. PMID- 21978750 TI - New look at nutritional care for obese patient candidates for bariatric surgery. AB - BACKGROUND: The combination of preoperative deficiencies and the restrictions and malabsorption possibly induced by bariatric surgery could lead patients to experience important nutritional deficits during the late postoperative period. Our objective was to characterize the eating, anthropometric, and biochemical profiles of obese candidates for bariatric surgery at a bariatric surgery center of a university hospital. METHODS: A retrospective study with the analysis of medical records of candidates for bariatric surgery from 2007 to 2008 was performed. A total of 80 adult patients, aged 45 +/- 11 years, were included in the present study. RESULTS: The mean patient weight was 145 +/- 24 kg, and the mean body mass index was 54 +/- 8 kg/m(2). Of the 80 patients, 78% had >=1 co morbidities related to obesity. The reported daily energy intake before surgery was 1981 +/- 882 kcal, with 48% +/- 11% consisting of carbohydrate, 29% +/- 8% of lipids, and 23% +/- 8% of protein. The mean number of daily meals was 4 +/- 1. Patients with a greater body mass index ingested a smaller amount of calories per kilogram of current weight. The occurrence of hyperglycemia, hyperuricemia, and dyslipidemia and of nutritional deficiencies, among them magnesium (19%), vitamin A (15%), vitamin C (16%), iron (9%), beta-carotene (3%), and vitamin B12 (3%), was high. CONCLUSION: The high occurrence of micronutrient deficiency detected by biochemical analysis in morbidly obese candidates for bariatric surgery, representing a disabsorptive process, might involve a poorer prognosis during the late postoperative period. A preoperative evaluation of the nutritional parameters and the food intake pattern is recommended for these patients, together with the necessary interventions. PMID- 21978751 TI - Pitfalls of bariatric tourism: a complication of gastric plication. PMID- 21978752 TI - Diet-induced obesity associated with steatosis, oxidative stress, and inflammation in liver. AB - BACKGROUND: Obesity induces steatosis and increases oxidative stress, as well as chronic inflammation in the liver. The balance between lipogenesis and lipolysis is disrupted in obese animals. At a cellular level, the changes in metabolic sensors and energy regulators are poorly understood. We hypothesized that diet induced steatosis increases oxidative stress, inflammation, and changes the metabolic regulators to promote energy storage in mice. The setting was a university-affiliated basic science research laboratory. METHODS: Four-week-old C57BL mice were fed a high-fat diet (n = 8) or regular chow (n = 8) for 7 weeks. The liver sections were stained for fat content and immunofluorescence. Liver homogenates were used for protein analysis by immunoblotting and mRNA analysis by reverse transcriptase-polymerase chain reaction. The gels were quantified using densitometry P <= .05 was considered significant. RESULTS: The high-fat diet upregulated protein kinase-C atypical isoforms zeta and lambda and decreased glucose tolerance and the interaction of insulin receptor substrate 2 with phosphoinositide kinase-3. The high-fat diet increased the transcriptional factors liver X receptor (4321 +/- 98 versus 2981 +/- 80) and carbohydrate response element-binding protein (5132 +/- 135 versus 3076 +/- 91), the lipogenesis genes fatty acid binding protein 5, stearoyl-co-enzyme A desaturase 1, and acetyl-co-enzyme A carboxylase protein, and fatty acid synthesis. The high fat diet decreased 5'-adenosine monophosphate-activated protein kinase (2561 +/- 78 versus 1765 +/- 65), glucokinase-3beta (2.214 +/- 34 versus 3356 +/- 86), and SIRT1 (2015 +/- 76 versus 3567 +/- 104) and increased tumor necrosis factor-alpha (3415 +/- 112 versus 2042 +/- 65), nuclear factor kappa B (5123 +/- 201 versus 2562 +/- 103), cyclooxygenase-2 (4230 +/- 113 versus 2473 +/- 98), nicotinamide adenine dinucleotide phosphate oxidase (3501 +/- 106 versus 1600 +/- 69) and reactive oxygen species production (all P < .001, obese mice versus lean mice). CONCLUSION: A high-fat diet impairs glucose tolerance and hepatic insulin signaling, upregulates transcriptional and translational activities that promote lipogenesis, cytokine production, proinflammatory signaling, and oxidative stress, and downregulates lipolysis. Understanding the complex cellular signals triggered by obesity might have profound clinical implications. PMID- 21978753 TI - Fundoplication combined with mediogastric plication. AB - BACKGROUND: The purpose of this pilot study was to demonstrate the feasibility and procedural safety of laparoscopic fundoplication combined with mediogastric plication in patients with a body mass index of 32-35 kg/m(2). METHODS: Sixteen patients underwent laparoscopic fundoplication combined with mediogastric plication. All procedures were performed with the patient under general anesthesia. The 1-year follow-up results encompassed gastroesophageal reflux disease recovery and excess weight loss. RESULTS: The procedure time varied from 65 to 95 minutes. No serious procedure-related complications occurred. Gastroesophageal reflux disease-related symptoms resolved in all patients (P = .000). The excess weight loss was 10 +/- 4 kg (58%) 1 year after the procedure. The 1-year follow-up excess weight was significantly less than the baseline excess weight (P = .000). The average body mass index decreased from 33.8 +/- 1.9 kg/m(2) at baseline to 27.2 +/- 1.7 kg/m(2) at 1 year (P = .02). Of the 16 patients, 14 had an excess weight loss of 62%, and 2 sweet-eaters had an excess weight loss of 33%. At 1 year of follow-up, the excess weight in those who smoked (n = 10) was greater than that of nonsmokers (n = 6; P = .02). However, smoking did not seem to significantly affect excess weight loss (P = .065). CONCLUSION: Fundoplication combined with mediogastric plication produced a total recovery from gastroesophageal reflux disease and an excess weight loss of 62% in 87.5% of patients after 1 year of follow-up. This procedure is technically feasible, and no serious procedure-related complications occurred. The follow-up is ongoing to investigate the efficacy and long-term durability of the procedure. PMID- 21978754 TI - Effect of PPAR-gamma agonist rosiglitazone on bone mineral density and serum adipokines in C57BL/6 male mice. AB - Thiazolinediones (TZD) are widely used to treat type 2 diabetes, but their mechanism of action still remains only partially understood. Although the in vitro effects of TZD on osteoblastogenesis are well recognized, the in vivo consequences of these compounds on bone turnover are less understood and rather controversial. We demonstrate that a 9-week oral treatment with rosiglitazone in C57BL/6 male mice resulted in significant bone loss that was not dose dependent. The bones of the rosiglitazone-treated mice were characterized by reduction of bone density, and ash, calcium and phosphorus content. Rosiglitazone-treated mice had significantly thinner cortical widths. In contrast to serum TrACP expressed by action of osteoclasts, serum B-ALP activity, which serves as a marker of osteoblastic activity, was significantly lower in the rosiglitazone-fed animals. We did not find any differences in circulating levels of adipokines that could eventually explain rosiglitazone action. As the decrease in osteoblastic activity was demonstrated after rosiglitazone treatment, we anticipated changes in the haematopoietic stem cell pool. These cells seed in endosteal niches which comprise osteoblasts in order to maintain their stem cell function. In our study we did not see any significant influence of rosiglitazone administration on stem cells or any impairment in the lineage restrictions of rosiglitazone-treated stem cells. Our data demonstrate that rosiglitazone administration causes a loss of bone mass in cortical bone, possibly through a decrease in bone formation expressed by decreased B-ALP in male C57BL/6 mice. The levels of adipokines do not play any role. PMID- 21978755 TI - RhoA distribution in renal caveolar fractions in experimental type 1 diabetes. AB - Caveolae act as signalling platforms serving as concentrating points for numerous signalling molecules, as well as regulating flux through many distinct signalling cascades. RhoA proteins have been identified as potential actors in the pathophysiology of the cardiovascular system. We used sucrose gradient fractionation and immunoblotting to determine caveolin-1 and RhoA presence in the kidney cortex of streptozotocin-induced T1 diabetes rats (4-week duration), and of diabetic rats treated with angiotensin receptor blocker losartan (4 weeks, 20 mg/kg/day) to retard renal hypertension. Positive RhoA/caveolin-1 co immunoprecipitation result was detected in the caveolar fraction that corresponded to the light-scattering band obtained from diabetic rats, compared to negative co-immunoprecipitation result in the caveolar fraction obtained from control rats. The detection of RhoA protein in the caveolar fractions and the prospective RhoA/caveolin-1 association can be used to examine the role of these signalling reactions in the pathophysiology of microvascular complications in type 1 diabetes. PMID- 21978756 TI - The influence of vascular endothelial growth factor (VEGF) polymorphism on the progression of chronic glomerulonephritides. AB - Vascular endothelial growth factor is an important mediator in maintaining normal kidney functions. In addition, several lines of evidence show that up-regulation of this mediator in glomeruli may be associated with or may directly cause renal dysfunction. We tried to assess the influence of the -2578 C/A and -1154 G/A polymorphisms in the regulatory region of the vascular endothelial growth factor gene upon progression of three primary chronic glomerulonephritides (minimal change disease/focal and segmental glomerulosclerosis, membranous nephropathy, immunoglobulin A nephropathy). We studied a cohort of 213 patients compared to 311 unrelated healthy controls. Analysis of the C/A polymorphism of vascular endothelial growth factor revealed an increased prevalence of CC genotype in the minimal change disease/focal and segmental glomerulosclerosis group in comparison with the other groups. A balanced distribution of G and A alleles among the respective types of chronic glomerulonephritides was shown in the analysis of 1154 G/A polymorphism. Finally, we have not proved any significant influence of the polymorphisms at positions -2578 C/A and -1154 G/A of the vascular endothelial growth factor gene promoter on the progression of chronic glomerulonephritides even though our study suggests a negative effect of CC genotype of -2578 C/A polymorphism on the clinical course of minimal change disease/focal segmental glomerulosclerosis. PMID- 21978757 TI - Methods for detection of circulating tumour cells and their clinical value in cancer patients. AB - Currently available analytical methods enable identification, detection and characterization of circulating tumour cells in the peripheral blood and disseminated tumour cells in the bone marrow of breast cancer patients. About 0.01 % of the circulating tumour cells observed in the blood are able to form metastases. Therefore, they could be used for estimation of the risk for metastatic relapse, as a diagnostic tool for patient stratification, early determination of the therapy failure, or potential risk of resistance to the given therapeutic intervention. New therapeutic molecular targets could be identified for management of cancer patients using circulating tumour cell detection. The following review summarizes introduced methods of circulating tumour cell detection and their possible application in clinics. PMID- 21978758 TI - Comparison of P19-derived neuroprogenitor and naive cell survival after intracerebellar application into B6CBA mice. AB - Mouse embryonic carcinoma cells (P19 line) were studied for both their survival and developmental potential in the intact cerebellum of B6CBA mice. The P19 cells were cultured and labelled with green fluorescent protein using transfection. Cells were used for transplantation either in the undifferentiated stage or after 3 days of neurodifferentiation induced by retinoic acid. The intracerebellar application was performed in 43 mice: group A (N = 21) received neuroprogenitors and group B (N = 22) received undifferentiated cells. The morphology of transplanted cells within the context of the surrounding cerebellar tissue was evaluated after 3 weeks. Naive P19 cells engrafted and survived in the cerebellum of 7 of the 22 adult mice (survival rate 31.8 %). Neuroprogenitors survived in 13 of the 21 mice (survival rate was 61.9 %). Since the cut-off is P < 0.05, the difference is not statistically significant (P = 0.069). An expansive appearance of the graft was significantly more frequent (P = 0.0047) in naive P19 cells than in neuroprogenitors. In mice in which the grafts did not survive, no marks of grafted cells or only fluorescing detritus were found. In conclusion, this is the first study to track the fate and morphology of embryonic carcinoma cells transplanted into the cerebellum, confirming that neuroprogenitors derived from embryonic carcinoma cells can settle in the host tissue and differentiate according to the surrounding conditions. With further validation, the embryonic carcinoma cells could become a valuable model with which to study the impact of cell therapy on neurodegenerative diseases. PMID- 21978759 TI - INSIG2 G-102A promoter variant exhibits context-dependent effect on HDL cholesterol levels but not on BMI in Caucasians. AB - The INSIG2 (INSIG2 is primarily involved in the regulation of fatty acid and cholesterol synthesis) gene is suggested to be obesity related. An INSIG2 promoter variant, G-102A, has been detected and was demonstrated to be of potential functional significance. In two cohorts of middle-aged men, the association between this variant and BMI was suggested. We sought to replicate the association between the INSIG2 G-102A variant and BMI in three large Slavonic Caucasian populations. Further, we analysed the possible effect of this variant on BMI changes in a short-time intervention study. One thousand ninety-nine males and 1368 females (population- based Czech MONICA three-year cohort), 908 females from the 3PMFs study, together with 94 overweight (BMI > 27 kg/m2) females who underwent nine weeks of dietary/exercise intervention were genotyped for the INSIG2 G-102A variant using PCR-RFLP analysis. We could not detect any association between the INSIG2 G-102A variant and BMI or WHR with or without adjusting for age and gender in any population. Neither the BMI change nor anthropometric and lipid parameter changes were affected by the INSIG2 G-102A gene variant in intervened overweight females. However, MONICA females (but not males) carrying the common GG genotype had higher plasma levels of HDL cholesterol (GG homozygotes 1.51 +/- 0.36 mmol/l vs. A allele carriers 1.45 +/- 0.33; P < 0.05) in both surveys. Our results indicated that the G-102A INSIG2 polymorphism has no consistent effect on BMI in general populations, but could influence HDL cholesterol in females. PMID- 21978760 TI - Association study of monoamine oxidase A/B genes and schizophrenia in Han Chinese. AB - BACKGROUND: Monoamine oxidases (MAOs) catalyze the metabolism of dopaminergic neurotransmitters. Polymorphisms of isoforms MAOA and MAOB have been implicated in the etiology of mental disorders such as schizophrenia. Association studies detected these polymorphisms in several populations, however the data have not been conclusive to date. Here, we investigated the association of MAOA and MAOB polymorphisms with schizophrenia in a Han Chinese population. METHODS: Two functional single nucleotide polymorphisms (SNPs), rs6323 of MAOA and rs1799836 of MAOB, were selected for association analysis in 537 unrelated schizophrenia patients and 536 healthy controls. Single-locus and Haplotype associations were calculated. RESULTS: No differences were found in the allelic distribution of rs6323. The G allele of rs1799836 was identified as a risk factor in the development of schizophrenia (P = 0.00001). The risk haplotype rs6323T-rs1799836G was associated with schizophrenia in female patients (P = 0.0002), but the frequency difference was not significant among male groups. CONCLUSIONS: Our results suggest that MAOB is a susceptibility gene for schizophrenia. In contrast, no significant associations were observed for the MAOA functional polymorphism with schizophrenia in Han Chinese. These data support further investigation of the role of MAO genes in schizophrenia. PMID- 21978761 TI - Ripped to death. AB - An old puzzle in the field of cell death was solved recently: the mysterious embryonic lethality of animals deficient in caspase-8 or Fas-associated death domain (FADD), proteins involved in a pathway of apoptosis. This lethality is caused by a failure to develop the yolk sac vasculature rather than a lack of apoptosis. Remarkably, development is rescued by ablation of either of two receptor interacting serine-threonine kinases (RIPKs). Despite being well known cell killers, caspase-8 and FADD act together to block RIPK-mediated necrosis. To manifest this newly elucidated pro-survival function, FADD and caspase-8 depend on FLIP(Long), a catalytically inactive caspase-8 homolog. In this review, the mechanism by which RIPK necrotic death is inhibited by this trio is discussed, as well as how RIPKs might themselves mediate cell death. PMID- 21978762 TI - K11-linked ubiquitin chains as novel regulators of cell division. AB - Modification of proteins with ubiquitin chains is an essential regulatory event in cell cycle control. Differences in the connectivity of ubiquitin chains are believed to result in distinct functional consequences for the modified proteins. Among eight possible homogenous chain types, canonical Lys48-linked ubiquitin chains have long been recognized to drive the proteasomal degradation of cell cycle regulators, and Lys48 is the only essential lysine residue of ubiquitin in yeast. It thus came as a surprise that in higher eukaryotes atypical K11-linked ubiquitin chains regulate the substrates of the anaphase-promoting complex and control progression through mitosis. We discuss recent findings that shed light on the assembly and function of K11-linked chains during cell division. PMID- 21978765 TI - Phase III trial of induction gemcitabine or paclitaxel plus carboplatin followed by paclitaxel consolidation in ovarian cancer. AB - OBJECTIVE: The safety and efficacy of gemcitabine plus carboplatin (GC) or paclitaxel plus carboplatin (TC) induction regimens with or without paclitaxel consolidation therapy were assessed in ovarian cancer (OC). METHODS: Patients with stage IC-IV OC were randomized to either GC (gemcitabine 1,000 mg/m(2), days 1 and 8, plus carboplatin area under the curve [AUC] 5, day 1) or TC (paclitaxel 175 mg/m(2) plus carboplatin AUC 6, day 1) every 21 days for up to six cycles. Patients with complete response (CR) were allowed optional consolidation with paclitaxel 135 mg/m(2) every 28 days for <= 12 months. Patients without CR received single-agent crossover therapy at induction doses/schedules until CR, disease progression (PD), or unacceptable toxicity. PD or death in 636 patients was required to compare induction arms with 80% statistical power for progression free survival (PFS), the primary endpoint. RESULTS: Randomized induction therapy was received by 820 of 919 patients enrolled; 352 patients with CR received paclitaxel consolidation whereas 155 patients without CR received single-agent crossover therapy. PFS was similar for GC and TC (median, 20.0 and 22.2 months, respectively; P=.199). Despite high censoring rates (>52%), overall survival was longer for TC (median, 57.3 versus 43.8 months for GC; P=.013). Controlling for patient characteristics including performance status, residual tumor size, and tumor stage, there was no statistical difference in a multivariate analysis (HR=1.22; 95% CI=0.99-1.52; P=.067). CONCLUSIONS: GC does not improve PFS over TC as first-line induction chemotherapy in OC. Although favoring TC, overall survival analyses were limited by the study design and high censoring rates. PMID- 21978766 TI - Paediatric and adolescent trauma care within an integrated trauma system. AB - BACKGROUND: The aim of this study was to establish the profile and outcomes of paediatric major trauma care (PTMC) within an integrated inclusive regionalised trauma system. METHODS: Prospectively collected data from July 2001 to June 2009 from the Victorian State Trauma Registry of patients aged <18 years were reviewed. RESULTS: There were 1634 major trauma cases with a median (IQR) age of 13 (6-16) years and 69% were male. The median ISS (IQR) was 18 (16-26). There were 1361 patients treated at a major trauma centre of which 69% (n=943) were treated at the PMTC. Head injury (AIS>2) was the most frequent injury (n=950, 58%). Surgery was required in 39% (n=637) of all cases; 437 patients in the 10-17 year old group and 200 patients in the 0-9 year old group; the mortality was 6.6%. There were 530 patients (32.4%) ventilated in ICU; these had a median ISS (IQR) of 25 (17-34) and mortality of 7.4%. Improvements in risk-adjusted mortality have occurred as the years have progressed [adjusted OR 95% CI: 0.87 (0.76, 0.99)] and being treated at a Level 1 trauma centre was associated with lower adjusted odds of mortality [adjusted OR 95% CI: 0.27 (0.11, 0.68)]. CONCLUSION: The establishment of this integrated inclusive regionalised trauma system has been associated with progressively improving risk-adjusted mortality. The relatively low volume of major trauma requiring surgery in the 0-9 year old age group is notable, creating a challenging environment for maintaining skills and institutional preparedness. PMID- 21978764 TI - Genomic phenotyping of the essential and non-essential yeast genome detects novel pathways for alkylation resistance. AB - BACKGROUND: A myriad of new chemicals has been introduced into our environment and exposure to these agents can damage cells and induce cytotoxicity through different mechanisms, including damaging DNA directly. Analysis of global transcriptional and phenotypic responses in the yeast S. cerevisiae provides means to identify pathways of damage recovery upon toxic exposure. RESULTS: Here we present a phenotypic screen of S. cerevisiae in liquid culture in a microtiter format. Detailed growth measurements were analyzed to reveal effects on ~5,500 different haploid strains that have either non-essential genes deleted or essential genes modified to generate unstable transcripts. The pattern of yeast mutants that are growth-inhibited (compared to WT cells) reveals the mechanisms ordinarily used to recover after damage. In addition to identifying previously described DNA repair and cell cycle checkpoint deficient strains, we also identified new functional groups that profoundly affect MMS sensitivity, including RNA processing and telomere maintenance. CONCLUSIONS: We present here a data-driven method to reveal modes of toxicity of different agents that impair cellular growth. The results from this study complement previous genomic phenotyping studies as we have expanded the data to include essential genes and to provide detailed mutant growth analysis for each individual strain. This eukaryotic testing system could potentially be used to screen compounds for toxicity, to identify mechanisms of toxicity, and to reduce the need for animal testing. PMID- 21978768 TI - A rare case of penetrating atherosclerotic ulcer of the aorta. AB - We are reporting a case of 66 year-old man who presented to a regional hospital with sudden onset of inter-scapular pain, radiating to anterior chest. Initial assessment was unremarkable except for high blood pressure and computed tomography (CT) of chest showing an intramural haematoma in the thoracic descending aorta. He was transferred to our institution for the medical management of his blood pressure and intramural haematoma of the aorta. A transoesophageal echocardiography confirmed the diagnosis but in addition demonstrated a penetrating atherosclerotic ulcer (PAU). Subsequently CT aortogram revealed a slow leak from the PAU. Endovascular repair with stent-grafting was urgently performed. He improved clinically and remained well on discharge. This case demonstrated that PAU, although rare and often under-recognised, is potentially life-threatening and should be considered in the evaluation of chest pain. Multi-modality imaging techniques can aid the diagnosis and guide appropriate and timely management. PMID- 21978767 TI - Unadjuvanted pandemic H1N1 influenza vaccine in HIV-1-infected adults. AB - We evaluated the immune response to a 2009 influenza A (H1N1) unadjuvanted vaccine in HIV-infected patients and assessed the boosting effect of a second dose. HIV-infected adults were enrolled and scheduled to receive the H1N1 unadjuvanted vaccine containing 15MUg of A/California/7/2009 haemagglutinin. Anti H1N1 antibody titers were measured at enrollment and 4-8 weeks after each vaccination by using haemagglutination inhibition (HI) and virus neutralization (NT) assays. One hundred and four patients were analyzed. Seroconversion, as measured by using HI and NT assays, was observed in 52 (50.0%) patients and 49 (47.1%) patients, respectively, after the first dose. Seroconversion rate evaluated by using NT, but not HI, antibody titers was associated with HIV RNA levels of <400copies/ml (odds ratio, 3.21; 95% CI, 1.15-8.96). Other parameters, including CD4 cell count, were not associated with seroconversion. In a cohort that received two vaccine doses at a 4-8-week interval (n=54), the seroconversion rate and geometric mean titer for HI antibodies were 44.4% (95% CI, 30.8-58.1%) and 30.5 (95% CI, 19.9-46.9) after the first dose, respectively, and 48.1% (95% CI, 34.4-61.9%) and 39.0 (95% CI, 26.1-58.2) after the second dose, respectively. Among HIV-infected patients, the seroconversion rate was around 50% after the first dose of unadjuvanted vaccine. A second dose of vaccine had a limited boosting effect on immunity in this patient cohort. PMID- 21978769 TI - Dysregulation of the Fas/FasL system in mononuclear cells recovered from peritoneal fluid of women with endometriosis. AB - In endometriosis, regurgitating endometrial cells fail to undergo apoptosis and implant themselves outside the uterus, particularly in the peritoneum. We studied Fas and FasL behaviour by evaluating the percentages of mFas and mFasL-bearing mononuclear cells from peritoneal fluid, the level of Fas and FasL gene expression at both mRNA and protein levels in the same cells, and the sFas and sFasL values in peritoneal fluid of 80 endometriotic women, at four stages of disease severity. We found no variation in percentage of mFas-bearing mononuclear cells; high and unchanging levels of Fas mRNA and protein, and high and invariable sFas values. Overproduction of sFas antagonises mFas function and plays a role as a decoy in the peritoneal fluid. The mFasL-bearing mononuclear cells and protein levels decreased from the minimal to the severe stage of disease. In contrast to FasL protein, FasL mRNA was overexpressed throughout the course of the disease. sFasL values were high and increased as the disease worsened. Our results showed a non-linear ratio between FasL mRNA and FasL protein levels. Abnormally elevated FasL mRNA may be due to dysregulation in several mechanisms controlling mRNA turnover. The high level of sFasL would be expected to down-regulate FasL activity and compete with the membrane form for mFas binding. As a consequence, mFas-bearing mononuclear cells may be unable to kill and in turn, may themselves become targets for killing by FasL-expressing endometriotic cells. PMID- 21978770 TI - Does a lower carbohydrate protein substitute impact on blood phenylalanine control, growth and appetite in children with PKU? AB - BACKGROUND: In children with phenylketonuria (PKU), it is possible that high carbohydrate protein substitutes may adversely affect blood phenylalanine control. We evaluated if a low carbohydrate, 'ready-to-drink' protein substitute would impact on short term blood phenylalanine control, weight and appetite in children with PKU aged 3-10 years. METHODS: This was a 3-part, 5-week randomised, controlled, crossover study in which two different carbohydrate/protein equivalent ratios in protein substitute [control protein substitute (CPS) median 1:1; trial protein substitute (TPS) 0.5:1] were compared. The effects on feeding behaviour, weight change and phenylalanine concentrations were studied. Fourteen children (12 boys; median age 6.3 y, range 3 to 9.7 y) with PKU on diet were recruited from 2 treatment centres. RESULTS: Phenylalanine control did not deteriorate with TPS and remained unchanged between pre-study and CPS (p = 0.783). No statistical differences were noted in energy intake between the two study parts. Any changes in weight were similar between the two groups and there was limited change in feeding behaviour. CONCLUSION: This study suggests that the carbohydrate/protein-equivalent ratio of protein substitutes can be reduced to 0.5:1 with no loss of blood phenylalanine control or adverse effect on weight gain in children with PKU. PMID- 21978771 TI - Gaucher disease due to saposin C deficiency, previously described as non neuronopathic form--no positive effects after 2-years of miglustat therapy. AB - Gaucher disease occurs mainly as a result of a deficiency of the lysosomal enzyme beta-glucocerebrosidase activity. A rare variant form of Gaucher disease is known in which saposin C required for glucosylceramide degradation is deficient. In an earlier paper we described the first cases of two siblings with the non neuronopathic form of Gaucher disease caused by saposin C deficiency [Tylki Szymanska et al., 2007]. In this article, we present a follow up of clinical and biochemical findings in one patient who has been treated with miglustat for two years. We observed that administration of miglustat failed to exert any favorable effect on the clinical condition, haematological parameters and glucosylceramide level in the serum. In two individuals (described in this article) very slow deterioration of the peripheral and central nervous systems was observed. PMID- 21978772 TI - betaFTZ-F1 and Matrix metalloproteinase 2 are required for fat-body remodeling in Drosophila. AB - During metamorphosis, holometabolous insects eliminate obsolete larval tissues via programmed cell death. In contrast, tissues required for further development are retained and often remodeled to meet the needs of the adult fly. The larval fat body is involved in fueling metamorphosis, and thus it escapes cell death and is instead remodeled during prepupal development. The molecular mechanisms by which the fat body escapes programmed cell death have not yet been described, but it has been established that fat-body remodeling requires 20-hydroxyecdysone (20E) signaling. We have determined that 20E signaling is required within the fat body for the cell-shape changes and cell detachment that are characteristic of fat-body remodeling. We demonstrate that the nuclear hormone receptor betaFTZ-F1 is a key modulator of 20E hormonal induction of fat body remodeling and Matrix metalloproteinase 2 (MMP2) expression in the fat body. We show that induction of MMP2 expression in the fat body requires 20E signaling, and that MMP2 is necessary and sufficient to induce fat-body remodeling. PMID- 21978773 TI - Ventricular short-axis measurements in patients with pulmonary embolism: effect of ECG-gating on variability, accuracy, and risk prediction. AB - OBJECTIVE: To assess prospectively the intra- and interobserver variability, accuracy, and prognostic value of right and left ventricular short-axis diameter (RVd and LVd) measurements for risk stratification in patients with pulmonary embolism (PE) using ECG-gated compared to non-gated CT. MATERIALS AND METHODS: Sixty consecutive patients (33 women; mean age 58.7+/-10.3 years) with suspicion of PE underwent both non-gated and ECG-gated chest CT. RVd and LVd on four chamber views and intra- and interobserver agreements were calculated for both protocols. RVd/LVd ratios were calculated and were related to 30-days adverse clinical events using receiver operating characteristics with area-under-the curve (AUC) analyses. RESULTS: Both inter- and intraobserver variability showed narrower limits of agreement for all measurements with ECG-gated as compared to non-gated CT. Diameter measurements were significantly lower using non-ECG-gated CT as compared to ECG-gated CT for RVd and LVd (both p<.05). The AUC for the RVd/LVd ratio from ECG-gated CT was significantly larger than that from non-gated CT (0.956, 95% CI: 0.768-0.999 versus 0.675, 95% CI: 0.439-0.860; p=.048). CONCLUSION: RVd and LVd measurements from ECG-gated chest CT show less intra- and interobserver variability and more accurately reflect ventricular function. In our patient cohort ECG-gated chest CT allows better prediction of short-term outcome of patients with acute PE that needs to be validated in a larger outcome study. PMID- 21978774 TI - Fluid-fluid level in hepatic metastases: a characteristic sign of metastases of neuroendocrine origin. AB - OBJECTIVES: The aim of this study is to determine MRI characteristics which indicate liver metastases of neuroendocrine tumors (NET) rather than metastases of other origin (non-NET). METHODS: Sixty-nine patients with histopathologically proven liver metastases from NET and 69 patients with known liver metastases of other origin underwent MRI of the liver using a 1.5 T MR-scanner. Two board certified radiologists assessed presence of fluid-fluid-levels, number and distribution pattern, signal intensity (SI) characteristics, lesion homogeneity, presence of central necrosis and intratumoral hemorrhage in T2w and T1w non contrast imaging. A multivariate logistic regression analysis was performed to determine the independent association of image findings and occurrence of NET. RESULTS: Fluid-fluid-levels were identified in 19/69 of patients with NET metastases, and in none of the patients in the control group (p<0.0001). Hyperintense SI in T1w imaging, markedly hyperintense SI in T2w imaging, a disseminated distribution pattern and intratumoral hemorrhage were indicative of NET metastases (p<0.05). After statistical adjustment for all significant MRI findings, fluid-fluid-levels (OR: 17.6, 95% CI: 1.9-166.5), strongly hyperintense SI in T2w (OR: 4.7, 95% CI: 1.8-12.7) and a disseminated distribution pattern (OR: 2.9, 95% CI: 1.1-7.4) were independent predictors for NET metastases. CONCLUSIONS: The presence of fluid-fluid-levels is highly indicative of NET liver metastases and can be used as an independent predictor to distinguish them from metastases of other origin. PMID- 21978775 TI - Selective and sequential transarterial chemoembolization: survival in patients with hepatocellular carcinoma. AB - PURPOSE: To assess the survival time of patients with HCC following transarterial chemoembolization performed in a highly selective and sequential way. PATIENTS AND METHODS: 124 HCC patients (102 male, 22 female; mean age 63+/-11 years) treated with selective and sequential chemoembolization at a single center were included. Selective chemoembolization was performed through a coaxially introduced microcatheter in a segmental or subsegmental hepatic artery. Treatment was stopped after complete stasis of the blood flow in the tumor-feeding vessel. The primary endpoint of the study was overall survival. RESULTS: The median overall survival of the entire patient population was 27.2 months (mo) (+/-8.9 mo, 95% CI 9.8 mo, 44.6 mo). When stratified according to liver function the median survival was 46.1 mo (+/-9.0 mo; 95% CI 28.5 mo, 63.7 mo) for Child-Pugh A and 11.1 mo (+/-4.3 mo; 95% CI 2.7 mo, 19.5 mo) for Child-Pugh B (p<.001). The median survival was 46.1 mo (+/-16.6 mo; 95% CI 13.5 mo, 78.7 mo) for BCLC stage A, 19.7 mo (+/-2.6 mo; 95% CI 14.6 mo, 24.8 mo) for BCLC stage B, and 14.4 mo (+/ 5.0 mo; 95% CI 4.5 mo, 24.3 mo) for BCLC stage C (p<.01). CONCLUSION: Selective and sequential chemoembolization offers long survival times in patients with HCC. Those patients with preserved liver function benefit more than patients with limited liver reserve. PMID- 21978776 TI - Yesterday's ethics in contemporary medicine - is it still of concern? AB - Discussions on questions and problems of medical ethics are on everyone's lips. The debates center for instance around the just allocation of public resources, demographical changes in our society or the guarantee of patient autonomy, thus posing questions on the technical progress in modern medicine. These contemporary conflicts in medicine are numerous, but not all of them are new; rather, the discussion in medical ethics on these dilemmas is bound to contexts and has historical roots. Some of these conflicts reach back to the medicine of the Renaissance and Antiquity, thus assigning actuality to the historical viewpoint. Taking history into account, one can benefit from a timeless content and not least get a feeling for historicity and contingency. Considering the creation of identity, the old authorities also represent central normative reference points for the ethical competence of physicians understood as an attitude within an interpersonal medicine. For this reason, the heritage of Hippocrates, which encompasses values and norms of the Hippocratic Oath, needs to be respected. Apart from other dimensions of knowledge and skills, the development of an individual ethical competence also requires awareness of the past, leading to an understanding for the historical, social and cultural relativity of medical action. PMID- 21978777 TI - A comparative analysis of primary and secondary Gleason pattern predictive ability for positive surgical margins after radical prostatectomy. AB - To compare the predictive ability of primary and secondary Gleason pattern for positive surgical margins in patients with clinically localized prostate cancer and a preoperative Gleason score <= 6. A retrospective analysis of the medical records of patients undergone a radical prostatectomy between January 2005 and October 2010 was conducted. Patients' age, prostate volume, preoperative PSA, biopsy Gleason score, the 1st and 2nd Gleason pattern were entered a univariate and multivariate analysis. The 1st and 2nd pattern were tested for their ability to predict positive surgical margins using receiver operating characteristic curves. Positive surgical margins were noticed in 56 cases (38.1%) out of 147 studied patients. The 2nd pattern was significantly greater in those with positive surgical margins while the 1st pattern was not significantly different between the 2 groups of patients. ROC analysis revealed that area under the curve was 0.53 (p=0.538) for the 1st pattern and 0.60 (p=0.048) for the 2nd pattern. Concerning the cases with PSA <10 ng/ml, it was also found that only the 2nd pattern had a predictive ability (p=0.050). When multiple logistic regression analysis was conducted it was found that the 2nd pattern was the only independent predictor. The second Gleason pattern was found to be of higher value than the 1st one for the prediction of positive surgical margins in patients with preoperative Gleason score <= 6 and this should be considered especially when a neurovascular bundle sparing radical prostatectomy is planned, in order not to harm the oncological outcome. PMID- 21978778 TI - Nicotine influences the motor performance of immature rats in two different sensorimotor tasks. AB - The aim of this study was to assess the effect of nicotine on motor performance of immature (12-day-old) rats. We used two sensorimotor tasks (surface righting response and negative geotaxis test) to evaluate the influence of nicotine on animal's motor activity in course of 24 hours. Animals were treated intraperitoneally with two different nicotine doses (0.5 mg/kg and 1.0 mg/kg) and tested in four sessions (1 minute, 10 minutes, 1 hour and 24 hours after the injection). We concluded that nicotine significantly influences the motor behaviour in 12-day-old rats and this effect is dose dependent. PMID- 21978779 TI - Is there circadian variation in cortisol levels in young sows in heart catheterization? AB - Cortisol is the main glucocorticoid (GC) hormone in pigs associated with stress response. It is well known that GCs levels are not stable during the day; their concentration is a circadian variable with the peak in the morning and the nadir in the night (in diurnal animals). Circadian variation is present during postnatal ontogeny. The onset of the circadian fluctuation occurs in pigs at the age of 3 to 20 weeks (according to the literature). The aim of our pilot study was to determine if young sows (used in cardiosurgical experiments) already developed the circadian variation. Twelve-week-old sows were used in the heart catheterization experiment. Cortisol was measured during four different stages of the experiment at two different times of the day (the operation was performed in the morning or afternoon). To determine circadian variation the Mann-Whitney test was used; to determine changes in cortisol levels within the experiment the Friedman test was performed. We didn't find any circadian variation (p>0.05) or statistical significant variation in the Friedman test (p>0.05). We assumed that our pigs are too young to have circadian rhythm present. Our findings are in accordance with many authors. PMID- 21978780 TI - Is learning ability and spatial memory in rats influenced by single dose of nicotine? AB - A lot of studies have been concentrated on an effect of a short or a long-term administration of nicotine in humans or in animals. The negative effects on the human organism have been known for a long time, but these health problems are known especially from observing smokers. The number of tasks in human and in animals with accent on positive effect of nicotine has increased especially with regard to improvement of cognitive functions. The aim of this study was to investigate, how much a single dose of nicotine can influence the learning ability in rats. Male Wistar albino rats, 25-day-old, were studied. Two groups of animals received an intraperitoneal (i.p.) injection of nicotine in two different doses (0.75 mg/kg and 1.00 mg/kg b.w.). The third group received a single i.p. injection of saline in the equal volume (the control group). After the drug application the escape latency and the path length were measured and assessed in two periods of sessions in the Morris water maze. In our study no explicit changes of learning ability after a single nicotine injection was confirmed. Only at the third day of the task the trajectory was shorter (p<0.05) but this result appears too isolated. So we cannot exclude that such improvement was caused by other factors than by the nicotine administration. PMID- 21978781 TI - TREM-1 expression on monocytes is not a parameter specific for infectious etiology of systemic inflammatory response syndrome. AB - Determination of mTREM-1 expression on monocytes has been investigated as a perspective diagnostic method to distinguish infectious from non-infectious etiology of the inflammation. THE AIMS OF OUR STUDY WERE: i) to investigate the expression of TREM-1 on monocytes in septic patients and in those after elective spinal surgery without infection; ii) to assess the dynamics of mTREM-1 expression on monocytes and its association with the outcome in patients with severe sepsis. Fifty two patients with severe sepsis, 20 healthy volunteers, and 20 patients after elective spinal surgery were involved in our study. TREM-1 expression on monocytes was evaluated by flow cytometry. Compared with the group of healthy adults (median 42.0, interquartile range (IQR) 30.3-76 MFI), mTREM-1 expression was increased in the group of septic patients both at entry (median 138.4, IQR 78.4-187.5 MFI) and the last examination (median 136.5, IQR 69.0-170.0 MFI) as well as in patients 24 hours after spinal surgery (median 138.5, IQR 45.3 165.5 MFI). The increase was statistically significant. mTREM-1 expression in patients undergoing spinal surgery and those with severe sepsis did not differ. TREM-1 expression on the monocytes in survivors was higher than in non-survivors (p=0.007). TREM-1 levels in septic non-surviving patients correlated weakly with TNF-alpha levels (r=0.38; p=0.003) and with HLA-DR/CD14 levels (r=0.38; p=0.003). Increased TREM-1 expression on monocytes is not associated exclusively with the presence of systemic infection. PMID- 21978782 TI - Patients with special needs within treatment under general anesthesia - meta analysis. AB - The study evaluates results obtained from the documentation of patients with special needs, who have undergone treatment under general anesthesia at the pediatric dentistry department. DMFT (decayed, missing, filled teeth) was used for comparison. A sample of 1,836 children from our dental clinic was evaluated. The sample was divided into two groups - special patient and disabled patient populations. A group of 5 years old children was chosen on the bases of WHO guidelines for the setting of the oral health status. A descriptive statistical analysis of the mean standard deviation was conducted with a focus on three factors: sex, age and year. A questionnaire was prepared to compare the oral health habits in the families of the patients. A literary review was conducted to compare the results with other studies from various countries. The meta-analysis using the software MedCalc was done. The DMFT of the patient was counted (disabled DMFT 11.05 - SD 4.82, special patient population 8.8 - SD 3.7) and the descriptive statistics mean standard deviation was calculated. The significant difference between the DMFT of disabled patient and special patient population was exerted (p<0.00003). It was statistically evaluated that the data gained from the studies and from the WHO as population average for 5 years old children are situated under the minimum limit of the confidence interval for our study. The meta-analysis confirmed the hypothesis that oral health status of the special needs children is worse than in other countries. PMID- 21978783 TI - Envenoming after a snakebite from the Northeast African saw-scaled viper Echis pyramidum: prolonged therapy upon failed treatment by antivenom. AB - A reptile holder based in the Czech Republic was bitten into his hand and foot by the Northeast saw-scaled viper (Echis pyramidum). The person arrived at the health institution after twenty hours for anuria. Despite the antivenom against the Asian Echis carinatum - the Echis pyramidum's close relative - was readily available and administered repeatedly, the envenoming continued to develop with subsequent coagulopathy, hepatopathy and respiratory failure. The effects of plasmapheresis and symptomatic therapy were positive, but only temporary. Continual renal replacement therapy and plasmapheresis were complicated by thrombotic occlusions of the device tubing set. A turning point arrived following repeated application of imported antivenom containing antigens against venom components of another African saw-scaled viper species, Echis leucogaster (the antivenom containing E. pyramidum antigens was not available). The clinical status, including complications, resolved following 30 days of hospitalization. The case further validates the geographical specifics of immunogenicity of venom components with similar clinical action in snakes of the same genus. PMID- 21978784 TI - 60 years of sleep medicine at the Department of Neurology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague. PMID- 21978785 TI - (-)-Epigallocatechin-3-gallate blocks 3T3-L1 adipose conversion by inhibition of cell proliferation and suppression of adipose phenotype expression. AB - AIMS: A major objective in the treatment of obese individuals is the development of agents that reduce body fat and improve metabolic homeostasis. Among a variety of biological effects, green tea exerts an anti-obesity effect; however, the mechanisms behind its activity on adipose tissue are uncertain. Tea contains high levels of (-)-epigallocatechin-3-gallate (EGCG), which is one of its main bioactive substances. Therefore, we studied the effects of EGCG on mouse embryonic fibroblast-adipose like cell line (3T3-L1) preadipocyte proliferation and differentiation. MAIN METHODS: 3T3-L1 cells were incubated with physiologically attainable (0.1-1 MUM) and pharmacological (5MUM, 10MUM) concentrations of EGCG for various lengths of time. Cell proliferation was assessed by cell counting and cell cycle analysis. Adipose conversion was evaluated by lipid accumulation and expression of CCAAT/enhancer binding protein alpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma (PPARgamma) transcription factors. KEY FINDINGS: A dose dependent suppressive effect on preadipocyte proliferation was observed, with the highest reduction in cell number at 10MUM EGCG. On the other hand, adipose conversion was fully inhibited with 10MUM EGCG. Flow-cytometric analysis showed that 3T3-L1 cells treated with EGCG underwent an arrest of cell cycle at G2/M. The inhibition of the expression of C/EBPalpha and PPARgamma was accompanied by the inhibitory effect of EGCG. Microscopic observation showed that 3T3-L1 cells treated with EGCG maintained the fibroblastic shape and failed to accumulate cytoplasmic fat droplets even after the induction of differentiation. SIGNIFICANCE: Our results suggest that EGCG reduces adipogenesis through an arrest of cell cycle and a blockage of adipose phenotype expression. These results also suggest that the anti-obesity activity of green tea may be partially attributed to its suppressive effects in adipogenesis. PMID- 21978786 TI - Aloe-emodin as antiproliferative and differentiating agent on human U937 monoblastic leukemia cells. AB - AIMS: Aloe-emodin (AE), a plant derived anthraquinone, has been shown to have anticancer activity in various human cancer cell lines. We have recently reported that AE possesses a differentiative potential on melanoma cells. The purpose of this study was to investigate the possible modulation of defined markers of monocytic differentiation of AE on human U937 cell line. MAIN METHODS: U937 cells differentiation has been confirmed unequivocally by Griess and nitroblue tetrazolium reduction assays, protoporphyrin IX accumulation, expression of CD14 and CD11b surface antigens, phagocytic activity, migration and attachment ability. The effect on polyamine metabolism, apoptosis and cytokine production was also investigated. KEY FINDINGS: We showed that AE-treated U937 cells exhibit a noticeably rise in transglutaminase activity. This enhanced enzyme activity correlates with AE-induced growth arrest and differentiation to functionally mature monocytes. SIGNIFICANCE: Taken together, the results reported here show that AE can promote the macrophage differentiation of U937 cells, suggesting that this anthraquinone could be a potential candidate as a differentiation-inducing selective agent for therapeutic treatment of leukemia. PMID- 21978787 TI - Muscle co-contraction after anterior cruciate ligament reconstruction: Influence of functional level. AB - BACKGROUND: ACL reconstruction is recommended to improve function in subjects with ligament injuries. However, after surgery, some individuals are not able to return to their pre-injury functional level. The mechanisms related to this incapacity are not well understood. STUDY DESIGN: Cross-sectional study. METHODS: Co-contraction levels were assessed in individuals who returned to their pre injury functional level and in 10 individuals who were not able to return to full activity after unilateral ACL reconstruction. Electromyography of the vastus lateralis and biceps femoris muscles before and after sudden perturbations applied during the stance phase of walking was used to calculate co-contraction. RESULTS: The involved limb had lower co-contraction pre-perturbation than the non involved limb in both groups (p=0.049). The co-contraction level post perturbation was significantly higher in the limited return group than in the full return group (p=0.03). CONCLUSION: Decreased co-contraction in the involved limb before perturbation may be caused by sensorial changes resulting from surgery or injury. Increased co-contraction levels observed in the limited return group after perturbation may be a compensatory mechanism to make up for possible decreased intrinsic stability of the knee joint. CLINICAL RELEVANCE: Increased co contraction after perturbation does not contribute to knee stability. PMID- 21978788 TI - Direction-specific recruitment of rotator cuff muscles during bench press and row. AB - Recent studies indicate that rotator cuff (RC) muscles are recruited in a reciprocal, direction-specific pattern during shoulder flexion and extension exercises. The main purpose of this study was to determine if similar reciprocal RC recruitment occurs during bench press (flexion-like) and row (extension-like) exercises. In addition, shoulder muscle activity was comprehensively compared between bench press and flexion; row and extension; and bench press and row exercises. Electromyographic (EMG) activity was recorded from 9 shoulder muscles sites in 15 normal volunteers. All exercises were performed at 20, 50 and 70% of subjects' maximal load. EMG data were normalized to standard maximal voluntary contractions. Infraspinatus activity was significantly higher than subscapularis during bench press, with the converse pattern during the row exercise. Significant differences in activity levels were found in pectoralis major, deltoid and trapezius between the bench press and flexion exercises and in lower trapezius between the row and extension exercises. During bench press and row exercises, the recruitment pattern in each active muscle did not vary with load. During bench press and row exercises, RC muscles contract in a reciprocal direction-specific manner in their role as shoulder joint dynamic stabilizers to counterbalance antero-posterior translation forces. PMID- 21978789 TI - Fish the ChIPs: a pipeline for automated genomic annotation of ChIP-Seq data. AB - BACKGROUND: High-throughput sequencing is generating massive amounts of data at a pace that largely exceeds the throughput of data analysis routines. Here we introduce Fish the ChIPs (FC), a computational pipeline aimed at a broad public of users and designed to perform complete ChIP-Seq data analysis of an unlimited number of samples, thus increasing throughput, reproducibility and saving time. RESULTS: Starting from short read sequences, FC performs the following steps: 1) quality controls, 2) alignment to a reference genome, 3) peak calling, 4) genomic annotation, 5) generation of raw signal tracks for visualization on the UCSC and IGV genome browsers. FC exploits some of the fastest and most effective tools today available. Installation on a Mac platform requires very basic computational skills while configuration and usage are supported by a user-friendly graphic user interface. Alternatively, FC can be compiled from the source code on any Unix machine and then run with the possibility of customizing each single parameter through a simple configuration text file that can be generated using a dedicated user-friendly web-form. Considering the execution time, FC can be run on a desktop machine, even though the use of a computer cluster is recommended for analyses of large batches of data. FC is perfectly suited to work with data coming from Illumina Solexa Genome Analyzers or ABI SOLiD and its usage can potentially be extended to any sequencing platform. CONCLUSIONS: Compared to existing tools, FC has two main advantages that make it suitable for a broad range of users. First of all, it can be installed and run by wet biologists on a Mac machine. Besides it can handle an unlimited number of samples, being convenient for large analyses. In this context, computational biologists can increase reproducibility of their ChIP-Seq data analyses while saving time for downstream analyses. PMID- 21978790 TI - Germ plasm in Eleutherodactylus coqui, a direct developing frog with large eggs. AB - BACKGROUND: RNAs for embryo patterning and for germ cell specification are localized to the vegetal cortex of the oocyte of Xenopus laevis. In oocytes of the direct developing frog Eleutherodactylus coqui, orthologous RNAs for patterning are not localized, raising the question as to whether RNAs and other components of germ plasm are localized in this species. METHODS: To identify germ plasm, E. coqui embryos were stained with DiOC6(3) or examined by in situ hybridization for dazl and DEADSouth RNAs. The cDNAs for the E. coqui orthologues were cloned by RT-PCR using degenerate primers. To examine activity of the E. coqui orthologues, RNAs, made from constructs of their 3'UTRs with mCherry, were injected into X. laevis embryos. RESULTS: Both DiOC6(3) and dazl and DEADSouth in situs identified many small islands at the vegetal surface of cleaving E. coqui embryos, indicative of germ plasm. Dazl was also expressed in primordial germ cells in the genital ridge. The 3'UTRs of E. coqui dazl and DEADSouth directed primordial germ cell specific protein synthesis in X. laevis. CONCLUSIONS: E. coqui utilizes germ plasm with RNAs localized to the vegetal cortex to specify primordial germ cells. The large number of germ plasm islands suggests that an increase in the amount of germ plasm was important in the evolution of the large E. coqui egg. PMID- 21978791 TI - Ambulant adults with spastic cerebral palsy: the validity of lower limb joint angle measurements from sagittal video recordings. AB - BACKGROUND: In the development of a clinical program for ambulant adults with cerebral palsy (CP), we investigated the validity of joint angles measured from sagittal video recordings and explored if movements in the transversal plane identified with three-dimensional gait analysis (3DGA) affected the validity of sagittal video joint angle measurements. METHODS: Ten observers, and 10 persons with spastic CP (19-63 years), Gross Motor Function Classification System I-II, participated in the study. Concurrent criterion validity between video joint angle measurements and 3DGA was assessed by Bland-Altman plots with mean differences and 95% limits of agreement (LoA). Pearson's correlation coefficients (r) and scatter plots were used supplementary. Transversal kinematics >=2 SD from our reference band were defined as increased movement in the transversal plane. RESULTS: The overall mean differences in degrees between joint angles measured by 3DGA and video recordings (3 degrees , 5 degrees and -7 degrees for the hip, knee and ankle respectively) and corresponding LoA (18 degrees , 10 degrees and 15 degrees for the hip, knee and ankle, respectively) demonstrated substantial discrepancies between the two methods. The correlations ranged from low (r=0.39) to moderate (r=0.68). Discrepancy between the two measurements was seen both among persons with and without the presence of deviating transversal kinematics. CONCLUSION: Quantifying lower limb joint angles from sagittal video recordings in ambulant adults with spastic CP demonstrated low validity, and should be conducted with caution. This gives implications for selecting evaluation method of gait. PMID- 21978792 TI - Influence of the structural deformity of the spine on the gait pathology in scoliotic patients. AB - Scoliosis is not only a spinal deformity, but also leads to the development of a pathological gait pattern. Nearly all studies examining walking in scoliotic patients report some degree of gait abnormality, however the results are somewhat contradictory. Therefore the aim of this study is to explore the relationship between gait pathology and degree of scoliotic deformity in a group of patients with idiopathic scoliosis. Sixty three females with idiopathic scoliosis, aged between 12 and 17 participated in the study. They were not treated previously, neither surgically, nor conservatively. They underwent objective gait analysis with a VICON 460 system. Data for the following parameters were analysed: gait velocity, cadence, step length, pelvic tilt, pelvic retraction, pelvic range of motion in the transverse plane, pelvic obliquity, hip and knee range of motion in the sagittal plane, knee flexion at initial contact, ankle dorsiflexion in swing, foot progression angle. Additionally a Gillette Gait Index (GGI) was calculated. Prior to the gait analysis all patients underwent a clinical examination, an X ray, clinical tests and anthropometric measurements. In conclusion our results indicate that the gait pathology of the patients with idiopathic thoraco-lumbar (i.e. double curve) scoliosis depends on the severity of the spinal deformity and the type of pelvic deformity. PMID- 21978793 TI - Effect of tones on vocal attack time in Cantonese speakers. AB - Vocal attack time (VAT) is the time lag between the growth of the sound pressure signal and the development of physical contact of vocal folds at vocal initiation. It can be derived by a cross-correlation of short-time amplitude changes occurring in the sound pressure and electroglottographic (EGG) signals. Cantonese is a tone language in which tone determines the lexical meaning of the syllable. Such linguistic function of tone has implications for the physiology of tone production. The aim of the present study was to investigate the possible effects of Cantonese tones on VAT. Sound pressure and EGG signals were simultaneously recorded from 59 native Cantonese speakers (31 females and 28 males). The subjects were asked to read aloud 12 disyllabic words comprising homophone pairs of the six Cantonese lexical tones. Results revealed a gender difference in VAT values, with the mean VAT significantly smaller in females than in males. There was also a significant difference in VAT values between the two tone categories, with the mean VAT values of the three level tones (tone 1, 3, and 6) significantly smaller than those of the three contour tones (tone 2, 4, and 5). The findings support the notion that norms and interpretations based on nontone European languages may not be directly applied to tone languages. PMID- 21978794 TI - The fate of the bodies of executed persons in the Anatomical Institute of Halle between 1933 and 1945. AB - In the period from 1933 to 1945 the Anatomical Institute in Halle (Saale) received bodies of persons, among them politically persecuted women and men, who had been sentenced to death and executed. In this article, we attempt to answer two important questions: (1) What happened to the bodies of those executed; i.e. which anatomical "purposes" did they serve? (2) Were anatomical specimens from these bodies added to the institute's anatomical collection and are they still present today? If so, can they be traced back to the bodies of politically persecuted people? So far we have discovered that between 1933 and 1936 the institute received 30 bodies, among them the bodies of two politically motivated death sentences. From 1937 until the end of 1942, only a few bodies arrived at the institute, and from November 1942 until the end of the war in 1945 the institute documented the transfer of 64 bodies of executed people. The death sentences pronounced during those early years were usually based on severe criminal acts (e.g. murder). During the war, special courts sentenced people to death mostly because of theft, looting, etc. The bodies of those executed were used in anatomical education, anatomical research, and in preparations of anatomical specimens to be added to the anatomical collection. There are eight macroscopic preparations which can definitely be associated with the bodies of people executed during the Nazi regime. Trial by jury sentenced those people to the maximum penalty because of the severity of their criminal acts. Up to now we have found no evidence that specimens of the anatomical collection were removed from bodies of victims whose execution was politically motivated. PMID- 21978795 TI - Switching on the deep brain stimulation: effects on cardiovascular regulation and respiration. AB - BACKGROUND: Objective of this study was to evaluate the acute cardiovascular and respiratory effects of switching on the deep brain stimulation in the follow up of nine Parkinson's disease patients with subthalamic nucleus stimulation and six cluster headache patients with posterior hypothalamic area stimulation. METHODS: Systolic and diastolic blood pressure, heart rate, and respiratory rate were monitored continuously during supine rest in both groups. Each patient was assessed in two conditions: resting supine with stimulator off and with stimulator on. RESULTS: In supine resting condition switching on the DBS induced no significant changes (p>0.05) in systolic and diastolic blood pressure as well as in heart rate and respiratory rate, in both groups of patients, either taking 1 min or 10 heartbeats as a sample for analysis. CONCLUSIONS: Switching on the DBS does not modify heart rate, blood pressure nor respiratory rate in both Parkinson and cluster headache patients under resting conditions. PMID- 21978796 TI - Effect of N-acetylcysteine treatment on oxidative stress and inflammation after severe burn. AB - Oxidative stress and inflammation generate edema in burns. The aim of our study was to assess effect of N-acetylcysteine (NAC) on oxidative stress, inflammation, fluid requirement, multiple organ dysfunction (MOD) score and vasoactive drug requirement. In this study 15 patients were on standard therapy, whereas for other 15 patients NAC was supplemented. Blood samples were taken on admission and on the next five consecutive mornings. Levels of malondialdehyde, protein sulfhydril (PSH) groups, reduced gluthation (GSH), activity of myeloperoxidase, catalase and superoxide dismutase enzymes and induced free radical generating capacity were measured as well as concentrations of TNF-alpha, IL-6, IL-8, and IL 10. MOD score, use of vasopressor agents and fluid utilisation were recorded daily. NAC treatment increased GSH level on days 4-5 (p<0.05) and PSH level on days 2-6 (p<0.05) compared to controls. Plasma IL-6 was lower on days 4-5 (p<0.05), IL-8 on days 4-6 (p<0.05) and IL-10 on days 4-6 (p<0.05) in NAC group. NAC group received less catecholamines than controls (p<0.01) from day 4 without significant differences in MOD score. NAC treatment is associated with a diminished oxidative stress reflected in preserved antioxidant levels, lower inflammation mirrored in lower interleukin levels and less vasopressor requirement. PMID- 21978798 TI - Global mental health in an interconnected, reciprocal world. PMID- 21978797 TI - [Human immunodeficiency virus infection and viral hepatitis]. AB - Hepatic complications currently represent one of the leading reasons for medical consultations, hospitalisation, and death in the HIV-infected population. This is due to a large extent to viral hepatitis, given its disproportionate frequency in this population. Chronic hepatitis B affects 5-10% of the HIV-infected population. Vaccination has reduced the incidence of liver disease related to hepatitis-B virus (HBV), and the availability of tenofovir has dramatically improved the prognosis of HIV/HBV carriers. Delta hepatitis affects around 15% of HIV-infected individuals in Europe harbouring positive HBsAg. It has the worst prognosis, given its accelerated course to cirrhosis and the absence of successful therapy. Lastly, chronic hepatitis C is the major cause of liver disease in the HIV population. Although classically linked to persons infected parenterally (i.e., intravenous drug users), outbreaks of acute hepatitis C among homosexual men have been reported over the last decade. Treatment with pegylated interferon plus ribavirin provides a cure in less than 40% of patients. However, the introduction of new direct acting antivirals against hepatitis- C virus (HCV) (telaprevir, boceprevir) has revolutionised the field, as HAART did in 1996 in the HIV field, improving the prognosis of co-infected patients. However, interactions between these drugs and antiretroviral agents and the risk of selective resistance pose huge threats in this population. PMID- 21978799 TI - Global focus, local acts: providing mental health services to indigenous people. AB - Four fundamental challenges to the provision of mental health services to indigenous populations are discussed, including proximity to services, community knowledge of mental health principles, human resource use, and cultural congruence. We describe concepts common to most indigenous approaches to mental well-being, including restoring health through balance and relatedness. Some strategies of practice are suggested to facilitate the cultural competence of psychiatric nurses and other mental health professionals who work with indigenous peoples. We contend that changes in availability of mental health services to indigenous peoples across the globe can be initiated with local actions by professionals who serve this population. PMID- 21978801 TI - Effectiveness of psychiatric mental health nurses: can we save the core of the profession in an economically constrained world? AB - Mental and behavioral disorders are common, affecting more than 25% of all people at some time during their lives. Mental disorders and their burden on society have increased dramatically. This scenario can be an opportunity for psychiatric/mental health (P/MH) nurses. Some literature shows gratifying experiences of care delivered by P/MH nurses, but that can also be a threat if, in a world with an economic dominance such as ours, we are not able to clarify our identity and effectiveness. One implication of this is that we need to identify the contribution of nursing to patient outcomes through nurses' independent, dependent, and interdependent roles. The authors stressed the importance of improving our accountability and fighting against invisibility to policy makers to prioritize the nurse-client relationship and identify our effectiveness. Based on some literature, the authors argue that clinical nurse specialists are in a better position than nurse practitioners to produce nursing sensitive outcomes. PMID- 21978800 TI - Nurse migration in an increasingly interconnected world: the case for internationalization of regulation of nurses and nursing regulatory bodies. AB - Psychiatric/Mental Health nursing has a long history of professional self regulation; nevertheless, interest in how governments protect consumers of health care from poor or dangerous practice(s) is on the increase. Correspondingly, there have been calls, in several parts of the world, for greater watchfulness and due diligence from regulatory bodies. Mindful of the concept of "globalization" and the unequivocal data regarding the significant increase in the migration of nurses, it is difficult to ignore/deny the reality of an increasingly mobile and connected international nursing workforce. However, the extant literature also indicates the existence of significant disparities between countries and even states/provinces within countries as to the enforcement of professional regulation. What this means is that decisions made by one regulatory body can have a direct impact on the standard(s) of nursing quality and practice in a country on the opposite side of the world. As a result, the authors attempt to advance the debate that there is a clear need to reconcile these positions, and they introduce the argument for the creation of an international oversight body. Using case study material, the relevant theoretical and policy literature in this area (such as it is), and by drawing on examples of analogous oversight bodies from other areas, we draw attention to the need to create a genuinely international body for the oversight of nurse regulation. PMID- 21978802 TI - Global perspective of burden of family caregivers for persons with schizophrenia. AB - Schizophrenia is a severe form of mental illness that affects about 7 per 1,000 of the adult population. It is estimated that globally about 29 million people have schizophrenia. With the advent of deinstitutionalization, most persons with schizophrenia are now being cared for in the community by their families. Living with a relative with severe mental illness is stressful. Burden of care is a global issue affecting family caregivers in both developed and developing countries. This article aims to examine the burden of family caregivers for persons with schizophrenia and the socioeconomic factors that influence the caregivers' perception of burden. There is a general agreement that family interventions are beneficial to family caregivers. Therefore, this article examines two of the most commonly investigated interventions: psychoeducation and support groups, for family caregivers of persons with schizophrenia. PMID- 21978803 TI - Mental health nursing and the politics of recovery: a global reflection. AB - The concept of recovery increasingly dominates mental health policy and practice agendas in most Western countries. However, the many, often conflicting, definitions of recovery have led to theoretical and practical confusion. More importantly, the concept clashes with some of the established assumptions of psychiatric/mental health nursing, especially the traditional notion that the person is "ill" and requires "treatment" or some other active "intervention." The implications of recovery for the further development of person-centered care, especially within a globalized form of mental health nursing, are discussed with specific reference to the Tidal Model, an international midrange theory of mental health nursing. PMID- 21978804 TI - Factors related to self-efficacy for social participation of people with mental illness. AB - This study investigated factors related to self-efficacy for social participation of individuals with severe mental illness (SMI). A total of 142 people with SMI recruited from a variety of rehabilitation programs completed an anonymous self report questionnaire that assessed self-efficacy for social participation, general self-efficacy, self-esteem, general mental health, social support, and life satisfaction. Employed participants reported significantly greater self efficacy for social participation, general self-efficacy, and life satisfaction than those who did not work. Participants using a day service reported having significantly fewer people providing social support than those not using one. Clinical implications and future direction for research are discussed. PMID- 21978805 TI - Subjective experiences of husbands of spouses with schizophrenia: an analysis of the husbands' descriptions of their experiences. AB - The caregiving experiences of husbands living with spouses with schizophrenia were described through exploring husbands' descriptions of their experiences. Twelve husbands participated in the study. According to content analysis, the husbands' experience revealed six major themes: identification and acceptance of the disease by the husbands, past and present experience with wives with schizophrenia, the roles and burdens of husbands, marital relationships and the presence of the wife for husbands, social resources, participation in the community and society, and perspectives on the future. Based on the bond of marriage established through living together and mutual trust between couples, the husbands aim to share life experiences with their wives. PMID- 21978806 TI - Women's experience of postpartum psychotic episodes--analyses of narratives from the internet. AB - The aim of this study was to gain an insight into women's experiences of postpartum psychosis (PPP). Ten narratives taken from the Internet, which met the definition of PPP, were analyzed using cross-case and content analyses. The results revealed women's experience of having unfulfilled dreams, being enveloped by darkness, having disabling symptoms, and being abandoned. The women's experiences point to the importance of further education of nurses and doctors concerning PPP. It is vital not only for those working in psychiatric health care but also midwives and nurses who are working in maternity wards and child welfare centers. This would facilitate early recognition of signs and symptoms of the disorder, which, in turn, would make early treatment possible, thus supporting recovery. Furthermore, greater knowledge could contribute to providing more effective and compassionate care for these women. PMID- 21978807 TI - Use of dolls as a therapeutic intervention: relationship to previous negative behaviors and pro re nata (prn) Haldol use among geropsychiatric inpatients. AB - This exploratory study was conducted to determine the effects of use of dolls as a therapeutic intervention with geriatric inpatients. The sample included 115 patients, 29 of whom had an order for prn Haldol. Among patients who had previous negative behaviors, there was a lower average number of prn Haldol doses with those who had dolls. Recommendations for practice and future research are included. PMID- 21978808 TI - Is recovery possible in a forensic hospital setting? PMID- 21978809 TI - Exploring patterns of seclusion use in Australian mental health services. AB - Seclusion has remained a common practice in mental health services. In Australia, recent mental health policy has reflected a desire to reduce (and, if possible, eliminate) the use of seclusion. The collection and analysis of data on the use of seclusion have been identified as an important component of the success of reduction initiatives. A cross-sectional design was used in the collection of inpatient unit data on seclusions that occurred in 11 mental health services in Australia over a 6-month period. During this time, there were 4,337 episodes of care. One or more seclusions occurred in 6.8% of episodes of care, with consumers being secluded, on average, 2.32 times and with 44% of them having been secluded more than once. The average length of the seclusions was 2 hours 52 minutes, with 51.4% of seclusions being less than 2 hours. These rates were lower than those reported in previous research studies. The practice of seclusion occurred more commonly on the first 2 days following admission, on weekdays than weekends, and between the hours of 9:00 a.m. and midnight. An understanding of seclusion data can provide fundamental information from which strategies to reduce seclusion can be developed. PMID- 21978810 TI - Differences in self-reported importance of elements of health and subjectively experienced health among outpatients in community mental health services. AB - Positive dimensions of mental health are strong protective factors against physical and mental illness in general population. A cross-sectional study including a randomly selected sample of 141 outpatients was performed to explore differences in patients' self-reported importance of elements of health and subjective experiences of health related to sociodemographic background variables. The examination of differences in self-reported importance of elements of health showed differences regarding gender, and the analyses of subjectively experienced health showed differences regarding age and diagnosis. Clinical interventions aiming at strengthening positive dimensions of health are required in community mental health services to meet the patients' individual needs of enhanced health. PMID- 21978811 TI - Utilization of the supports intensity scale with psychiatric populations: psychometric properties and utility for service delivery planning. AB - In agreement with the new paradigm of supports, this study examines the adequacy and psychometric properties of the Supports Intensity Scale (SIS) in a sample of 182 participants with severe mental illness (mean Global Assessment of Functioning [GAF] score = 60.2). The measure focuses on identifying the profile and intensities of support needs and on the planning and service delivery rather than on weaknesses and limitations. Internal consistency indexes ranged from .83 to .97; interrater reliability indexes ranged from .67 to .98. Intercorrelations among SIS subscales supported its construct validity. SIS scores correlated to GAF scores and length of disease. Discriminant analysis correctly classified 60.9% of participants. Therefore, the SIS demonstrated adequate reliability and validity, and it can be used by nursing professionals to plan for required supports in this population. PMID- 21978812 TI - Anti-inflammatory effects of sophocarpine in LPS-induced RAW 264.7 cells via NF kappaB and MAPKs signaling pathways. AB - Sophocarpine, a tetracyclic quinolizidine alkaloid, is one of the most abundant active ingredients in Sophora alopecuroides L. Our previous studies have showed that sophocarpine exerts anti-inflammatory activity in animal models. In the present study, anti-inflammatory mechanisms of sophocarpine were investigated in lipopolysaccharide (LPS)-induced responses in RAW 264.7 cells. Furthermore, the cytotoxicity of sophocarpine was tested. The results indicated that sophocarpine could increase the LDH level and inhibit cell viability up to 800MUg/ml, and which was far higher than that of the plasma concentration of sophocarpine in clinical effective dosage. The results also demonstrated that sophocarpine (50 and 100MUg/ml) suppressed LPS-stimulated NO production and pro-inflammatory cytokines secretion, including tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). These were associated with the decrease of the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, sophocarpine inhibited LPS-mediated nuclear factor-kappaB (NF kappaB) activation via the prevention of inhibitor kappaB (IkappaB) phosphorylation. Sophocarpine had no effect on the LPS-induced phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2), whereas it attenuated the phosphorylation of p38 mitogen-activated protein (MAP) kinase and c-Jun NH(2) terminal kinase (JNK). Our data suggested that sophocarpine exerted anti inflammatory activity in vitro, and it might attribute to the inhibition of iNOS and COX-2 expressions via down-regulation of the JNK and p38 MAP kinase signal pathways and inhibition of NF-kappaB activation. PMID- 21978813 TI - Prevalence, characteristics, and management of endometriosis in an infertile Maltese population. PMID- 21978814 TI - Dysgerminoma in the uterine cervix. PMID- 21978815 TI - Maternal sacral fracture during delivery causing foot drop. PMID- 21978816 TI - Pelvic node removal and disease-free survival in cervical cancer patients treated with radical hysterectomy and pelvic lymphadenectomy. AB - OBJECTIVE: To examine the relationship between the number of pelvic nodes removed and 5-year disease-free survival in early-stage cervical cancer patients who underwent radical hysterectomy and pelvic lymphadenectomy (RHPL). METHODS: The medical records of 826 cervical cancer patients who underwent RHPL and who had at least 11 pelvic nodes removed at Chiang Mai University Hospital between January 2002 and December 2008 were reviewed. The patients were divided into 4 groups according to the number of nodes removed: 11-20 nodes (n=243); 21-30 nodes (n=344); 31-40 nodes (n=171); and >= 41 nodes (n=68). The 5-year disease-free survival of patients in each group was compared. The clinicopathological factors were analyzed using Cox regression to identify independent prognostic factors. RESULT: Five-year disease-free survival was not significantly different among the 4 groups. When patients with and without nodal involvement were considered separately, the 5-year disease-free survival in all groups was not significantly different. At multivariate analysis, the number of pelvic nodes removed was not an independent prognostic factor. CONCLUSION: The number of pelvic nodes removed was not associated with 5-year disease-free survival or number of positive pelvic nodes. PMID- 21978817 TI - A new chapter: hematopoietic stem cells are direct players in immunity. AB - Several lines of evidence support the hypothesis that hematopoietic stem cells (HSCs) directly interact with the immune system and have potential for immune privilege. Although the microenvironment or niche provides protection for HSCs from immune attack, HSCs are also capable of interacting with the immune system as signal "providers" and signal "receivers". On the one hand, HSCs display surface immune inhibitory molecules to evade the attack from the innate and adaptive immune systems; on the other hand, HSCs are capable of directly sensing the signals from the immune system through their surface receptors. Thus, HSCs are important direct players in the immune system. PMID- 21978818 TI - Off label use of devices and drugs in interventional radiology. AB - AIM: To establish how often off-label device and drug use occurs in interventional radiology (IR) in a UK tertiary referral hospital and consider the wider implications for the interventional radiologist. MATERIALS AND METHODS: Prospective data were collected during interventional procedures for 1 working week in a university hospital. Out-of-hours procedures and procedures outside the department were excluded. Operators were asked to record the drugs and devices used, the indication, and method of use. The instructions for use/summary of product characteristics were then studied for each device/drug used to assess if the use was on or off-label. RESULTS: During the study period 52 cases were performed and data were available on 26 cases (50%). In 22 of the 26 cases (84%) there was evidence of off-label use of devices or drugs. Off-label use of drugs included treatment of venous malformations with Fibrovein((c)) (sodium tetradecyl sulphate), which is licensed for the treatment of varicose veins in the leg, and intra-arterial injection of heparin, which is licensed for intravenous and subcutaneous use. Off-label device use included placing vascular sheaths in the urinary tract, using angiographic catheters to guide wires in the urinary tract, using sheaths for thrombosuction, reshaping of the tip of most guidewires, and using angioplasty balloons to dislodge the arterial plug at fistula thrombectomy. CONCLUSION: Off-label device and drugs use is common in a UK tertiary hospital IR department and literature suggests this is common in the wider IR community. There are important clinical and legal implications for off-label use for patients and physicians. PMID- 21978819 TI - Antidiabetic activity of alcoholic stem extract of Gymnema montanum in streptozotocin-induced diabetic rats. AB - In the present study, the effect of alcoholic stem extract of Gymnema montanum (GMSt) on blood glucose, plasma insulin, and carbohydrate metabolic enzymes were studied in experimental diabetes. Diabetes mellitus was induced by a single intraperitoneal injection of STZ (60 mg/kg bw). Five days after STZ induction, diabetic rats received GMSt orally at the doses of 25, 50, 100 and 200mg/kg daily for 3 weeks. Graded doses of stem extract showed a significant reduction in blood glucose levels and improvement in plasma insulin levels. The effect was more pronounced in 100 and 200mg/kg than 50mg/kg. GMSt showed significant increase in hexokinase, Glucose-6-phosphate dehydrogenase and glycogen content in liver of diabetic rats while there was significant reduction in the levels of glucose-6 phosphatase and fructose-1,6-bisphosphatase. The present study clearly indicated significant antidiabetic effect with the stem extract of G. montanum and lends support for its traditional usage. PMID- 21978820 TI - [Accuracy of the door-to-balloon time for assessing the result of the interventional reperfusion strategy in acute ST-segment elevation myocardial infarction]. AB - BACKGROUND: In patients with acute ST-segment elevation myocardial infarction (STEMI), recent clinical guidelines recommend that primary percutaneous coronary intervention (PCI) should be performed within 90min of first medical contact or 45min after admission in cathlab. The Door-to-Balloon time (D2B) is widely used to measure the performance of interventional centres. AIM OF THE STUDY: To analyze the time to reperfusion in a consecutive series of STEMI patients referred for primary PCI, and to evaluate the clinical accuracy of D2B in primary PCI. METHODS: From January 2007 to March 2008, 177 patients were admitted within 12hours of a STEMI in our institution, and 87 were referred for a direct coronary angiography for primary PCI (47 by mobile medical emergency unit, 40 by the emergency department of the institution). RESULTS: The median time from first medical contact to balloon inflation (M2B) was 135min [IQR 112-183]. Recommended times were fulfilled in a minority of patients (M2B<90min: 9%,<120min: 34%). Median cathlab D2B was 51min [IQR 44-65], and was less than 45min in 34% of patients. No differences for times to reperfusion within cathlab were found between in- and off-time hours. M2B and D2B were unavailable in 23 patients (26%), because of a spontaneous TIMI 3 flow reperfusion without indication for immediate PCI in 20 patients, contra-indication for PCI in two (distal occlusion, culprit vessel diameter less than 2mm), and failure in occlusion crossing by the guide-wire in one patient. In contrast, first medical contact- or door-to reperfusion times, assessed by a TIMI 3 flow without no-reflow in culprit artery, were available in 95% of patients, and were shorter than M2B or D2B, respectively. CONCLUSION: Although it is a feasible and reproducible process performance measure, D2B time is weakly associated with the outcome of the interventional reperfusion strategy in acute STEMI. This measure should be associated with an outcome performance measure, such as the rate of TIMI 3 flow achieved by primary PCI, or replaced by the Door-to-TIMI 3 flow reperfusion time. PMID- 21978821 TI - [Pseudo-aneurysm of mitro-aortic continuity: a rare complication after aortic valve replacement]. AB - Pseudo-aneurysm of the fibrous continuity zone between the aortic and mitral valves, the so-called "mitral-aortic intervalvular fibrosa" is a rare complication of acute infective endocarditis, rarely after an aortic valve replacement. We report the case of a large pseudo-aneurysm occurred in a 70-year old man, who had a history of surgical aortic valve replacement 3 years before. There were no biological or clinical evidence for infective acute endocarditis. The originality of this observation can be summarized in three points: the late onset after surgery, the absence of any infectious context and the chronic nature of pseudo-aneurysm, without any complication during a follow-up of 12 months. Transesophageal echocardiography remains the best diagnostic tool. PMID- 21978822 TI - The function and phylogenetic implications of the tentorium in adult Neuroptera (Insecta). AB - Despite several recent analyses on the phylogeny of Neuroptera some questions still remain to be answered. In the present analysis we address these questions by exploring a hitherto unexplored character complex: the tentorium, the internal cuticular support structure of the insect head. We described in detail the tentoria of representatives of all extant neuropteran families and the muscles originating on the tentorium using 3D microCT images and analyzed differences in combination with a large published matrix based on larval characters. We find that the tentorium and associated musculature are a source of phylogenetically informative characters. The addition of the tentorial characters to the larval matrix causes a basad shift of the Sisyridae and clearly supports a clade of all Neuroptera except Sisyridae and Nevrorthidae. A sister group relationship of Coniopterygidae and the dilarid clade is further corroborated. A general trend toward a reduction of the dorsal tentorial arms and the development of laminatentoria is observed. In addition to the phylogenetic analysis, a correlation among the feeding habits, the development of the maxillary muscles, and the laminatentoria is demonstrated. PMID- 21978823 TI - Rostrum structure and development in the rice weevil Sitophilus oryzae (Coleoptera: Curculionoidea: Dryophthoridae). AB - A documentation and review of weevil rostrum growth is made through examination of the developmental life stages in the rice weevil Sitophilus oryzae (Linnaeus). Histological and morphological examinations are made utilizing light, fluorescent, and electron microscopy. In S. oryzae, rostral tissue begins proliferating in the late 4th instar larva and continues through to the pupal stage, with the majority of rostrum growth taking place in the prepupa. Adult cranial and rostral morphology is also reviewed, focusing on structures that may be pertinent to phylogeny reconstruction. The weevil rostrum is essentially an extension of various head sclerites that are basal to the mouthparts. Therefore, while the mouthparts are fairly similar to other Coleoptera in basic form, the head is markedly different due to its anterior extension. By understanding the more noticeable details of rostrum growth and structure, this study may serve as a foundation for comparative studies of a similar nature and as a basis for beginning research on the genetic nature of rostrum formation and evolution throughout the weevil clade. PMID- 21978824 TI - Morphology and histology of secretory setae in terrestrial larvae of biting midges of the genus Forcipomyia (Diptera: Ceratopogonidae). AB - Apneustic larvae of the genus Forcipomyia possess unique secretory setae located on the dorsal surface along the body in two rows, one pair on each thoracic and abdominal segment and two pairs on the head. Morphological and histological studies of secretory setae in fourth instar larvae of Forcipomyia nigra (Winnertz) and Forcipomyia nigrans Remm indicate they are modified mechanoreceptors (sensilla trichodea) in which the trichogen cell is a glandular cell producing a hygroscopic secretion. The cytoplasm of the glandular trichogen cell fills the lumen of a secretory seta, which shows one or more pores on the apex. The cytoplasm contains numerous microtubules responsible for transportation of proteinaceous vesicles, and an extremely large polyploid nucleus typical of gland cells. The main role of the hygroscopic secretion is to moist the body and thus facilitate cuticular respiration. PMID- 21978825 TI - FOXM1: From cancer initiation to progression and treatment. AB - The Forkhead box protein M1 (FOXM1) transcription factor is a regulator of myriad biological processes, including cell proliferation, cell cycle progression, cell differentiation, DNA damage repair, tissue homeostasis, angiogenesis and apoptosis. Elevated FOXM1 expression is found in cancers of the liver, prostate, brain, breast, lung, colon, pancreas, skin, cervix, ovary, mouth, blood and nervous system, suggesting it has an integral role in tumorigenesis. Recent research findings also place FOXM1 at the centre of cancer progression and drug sensitivity. In this review the involvement of FOXM1 in various aspects of cancer, in particular its role and regulation within the context of cancer initiation, progression, and cancer drug response, will be summarised and discussed. PMID- 21978827 TI - A target analogue imprinted polymer for the recognition of antiplatelet active ingredients in Radix Salviae Miltiorrhizae by LC/MS/MS. AB - The purpose of this study was to prepare a propyl gallate (PrG) molecular imprinted polymer as a cartridge stuffing material to isolate antiplatelet active ingredients. A macroporous polymer was synthesized utilizing ethylene glycol dimethacrylate (EDMA) as the crosslinking agent, PrG as the template molecule and 4-vinylpyridine (4-Vpy) as the functional monomer. Subsequently, PrG was removed by washing with methanol-glacial acetic acid (9:1, v/v). The molecular imprinted polymer recognized an active ingredient, protocatechuic acid, from a crude extract of the Chinese herbal medicine, Radix Salviae Miltiorrhizae (Danshen), using an on-line column switching solid phase extraction process. Pharmacological experiments showed that protocatechuic acid inhibits arachidonic acid (10 mg/kg) induced aggregation of rat platelets in vivo. This study provides an example of an application of separation-analysis technique for screening potentially bioactive compounds. PMID- 21978828 TI - Structure of the major degradant of ezetimibe. AB - In a recent contribution to this Journal Gajjar and Shah described the isolation and structure elucidation of the major alkaline degradant of ezetimibe, a lipid lowering agent [A.K. Gajjar, V.D. Shah, J. Pharm. Biomed. Anal. 55 (2011) 225 229]. Based on (1)H NMR, (13)C NMR and mass spectrometric studies the authors concluded that the structure of the degradant is 5-(4-fluorophenyl)-2-[(4 fluorophenylamino)-(4-hydroxyphenyl) methyl]-pent-4-enoic acid. In a subsequent "Letter to the Editor" submitted to the Journal, Barhate and Mohanra pointed out that the aforementioned structure is inconsistent with the spectroscopic data reported by Gajjar and Shah, consequently it must be wrong [Ch.R. Barhate, K. Mohanra, J. Pharm. Biomed. Anal. 55 (2011) 1237-1238]. However, Barhate and Mohanra did not offer a correct structure in their critical letter. Based on the cited NMR data we realised that previously we had had the same degradant in hand and had unambiguously determined its structure from detailed (1)H, (13)C, COSY, H C HSQC, H-C HMBC and 1D-NOESY NMR investigations. Herein we report the correct structure to be (2R,3R,6S)-N,6-bis(4-fluorophenyl)-2-(4-hydroxyphenyl)-3,4,5,6 tetrahydro-2H-pyran-3-carboxamide. However, the structure is not new and was described earlier [G.Y.S.K. Swamy et al., Acta Cryst. E 61 (2005) o3608-o3610; K. Filip et al., J. Mol. Struct. 991 (2011) 162-170]. The aim of our present communication is to bring together the various threads of analytical effort involving this degradant into a compact and hopefully instructive conclusion on the pages of this Journal. For the sake of completeness and clarity we also list the correct NMR spectral assignments for ezetimibe which was also given partly erroneously in the earlier literature, and we propose a mechanism for the formation of the degradant. PMID- 21978826 TI - The mitotic Clb cyclins are required to alleviate HIR-mediated repression of the yeast histone genes at the G1/S transition. AB - The histone genes are an important group of cell cycle regulated genes whose transcription is activated during the G1/S transition and repressed in early G1, late S, and G2/M. The HIR complex, comprised of Hir1, Hir2, Hir3 and Hpc2, regulates three of the four histone gene loci. While relief of repression at the G1/S boundary involves the HIR complex, as well as other cofactors, the mechanism by which this derepression occurs remains unknown. To better understand how transcriptional repression contributes to periodic expression in the cell cycle, we sought to identify the cell cycle signals required to alleviate HIR-mediated repression of the histone genes. By measuring histone gene transcription in strains with various combinations of clb mutations, we found that the mitotic Clb1/Clb2 cyclins are required to alleviate Hir-mediated repression during the G1/S transition and that Clb2 physically interacts with the HIR complex. While the HIR complex regulates histone gene transcription in combination with two other histone H3/H4 chaperones, Asf1 and Rtt106, our data demonstrate that the mitotic Clb cyclins are necessary to specifically alleviate the repressive action of the HIR complex itself in order to allow proper expression of the histone genes in late G1/early S phase. PMID- 21978829 TI - Local model for contextual modulation in the cerebral cortex. AB - A neural response to a sensory stimulus in cerebral cortex is modulated when other stimuli are presented simultaneously. The other stimuli can modulate responses even when they do not drive the neural output alone, indicating a non linear summation of synaptic activity. The mechanisms of the nonlinearity have remained unclear. Here, I explore a model which considers both network and intracellular processes, and which can account for various types of contextual modulation. The processes include synaptic sensitivity function, determination of inhibition strength, dendritic decay of membrane voltage, and summation of excitatory and inhibitory membrane voltages. First, the model assumes that excitatory and inhibitory units have the same input sensitivity function, which is more broadly tuned than the output tuning function. Second, a central property of the model is that inhibition is a fraction of excitation, determined by covariance between the input and the sensitivity function. With proper fraction, a model neuron sums apparently decorrelated input, regardless of correlations in the original input. Third, the model assumes that synaptic input lands anisotropically on the dendrites, which together with passive dendritic decay cause exponential decay in summation along the input space. This explains the difference between input sensitivity function and output tuning function, and thus accounts for the division between driving classical and modulating extra classical receptive fields. The model simulations replicate single-cell area summation function, far surround facilitation, and a shift in tuning function due to contextual stimulation. The model is very general, and should be applicable to various interactions between cortical representations. PMID- 21978830 TI - Down-regulation of FUT3 and FUT5 by shRNA alters Lewis antigens expression and reduces the adhesion capacities of gastric cancer cells. AB - BACKGROUND: Lewis antigens are fucosylated glycoconjugates involved in the development of several pathologies. The adhesion of sialyl-Lewis antigens to E selectin is a key step in the development of metastasis and the glycosidic component of CD44 plays a key role in the binding to hyaluronic acid, a component of the extracellular matrix associated to tumor development and invasion. Fucosyltransferases are enzymes that add fucose to precursor glycan structures: FUT3 and FUT5 catalyze the addition of fucose to the alpha1-3,4 position and are detected in epithelial cells. In this study, we have analyzed the effects of silencing FUT3, FUT5 or FUT3/FUT5, in two gastric cancer cell lines, in the expression of Lewis antigens and in the adhesive and migratory capacities of the cells. METHODS: FUT3, FUT5 and FUT3/FUT5 were down-regulated using lentiviral delivery of shRNAs in MKN45 and GP220 gastric cancer cells. RESULTS: In the infected cells, decreased levels of FUT3 and FUT5 mRNA detected by quantitative RT-PCR; and lower levels of sialyl-Lewis antigens, evaluated by flow cytometry, were observed. The adhesion to endothelial cells trough the binding to E selectin, and the binding to hyaluronic acid were reduced in the shFUT3, shFUT5 and shFUT3/FUT5, whereas the levels of CD44, analyzed by western blot, did not change. GENERAL SIGNIFICANCE: The down-regulation of FUT3, FUT5 and FUT3/FUT5 reduces the expression of sialyl-Lewis antigens and the adhesion and binding capacities of gastric cancer cells; and allows to identify the specific alpha1 3,4 fucosyltransferases implicated in the Lewis antigens synthesis in this cellular model. PMID- 21978831 TI - Enzymatic synthesis of mono and dinucleoside polyphosphates. AB - BACKGROUND: Mono and dinucleoside polyphosphates (p(n)Ns and Np(n)Ns) exist in living organisms and induce diverse biological effects through interaction with intracellular and cytoplasmic membrane proteins. The source of these compounds is associated with secondary activities of a diverse group of enzymes. SCOPE OF REVIEW: Here we discuss the mechanisms that can promote their synthesis at a molecular level. Although all the enzymes described in this review are able to catalyse the in vitro synthesis of Np(n)Ns (and/or p(n)N), it is not clear which ones are responsible for their in vivo accumulation. MAJOR CONCLUSIONS: Despite the large amount of knowledge already available, important questions remain to be answered and a more complete understanding of p(n)Ns and Np(n)Ns synthesis mechanisms is required. With the possible exception of (GTP:GTP guanylyltransferase of Artemia), all enzymes able to catalyse the synthesis of p(n)Ns and Np(n)Ns are unspecific and the factors that can promote their synthesis relative to the canonical enzyme activities are unclear. GENERAL SIGNIFICANCE: The fact that p(n)Ns and Np(n)Ns syntheses are promiscuous activities of housekeeping enzymes does not reduce its physiological or pathological importance. Here we resume the current knowledge regarding their enzymatic synthesis and point the open questions on the field. PMID- 21978832 TI - Visuospatial neglect in action. AB - It is well established that patients with hemispatial neglect present with severe visuospatial impairments, but studies that have investigated visuomotor control directly have revealed diverging results, with some investigations finding impairments mirroring the perceptual difficulties of these patients, while others have shown that such neglect patients perform relatively better in action tasks. In this review we attempt to reconcile these diverging findings, addressing differences in the type of visuomotor tasks studied but also highlighting the diverging neuroanatomy that seems to be driving the differences in performance. We argue that there are different types of actions and that these in turn depend on different cortical networks (Goodale, Westwood, & Milner, 2004; Milner & Goodale, 2006). Patients with visuospatial neglect, in contrast to patients with optic ataxia, are relatively unimpaired at performing target-directed tasks even towards stimuli located in their 'neglected' field. We relate these findings to the view that for the on-line guidance of action, spatial information is coded in egocentric coordinates and depends on the visuomotor networks of the visual dorsal stream. Furthermore, based on recent lesion-symptom mapping studies, we postulate that deficits in on-line actions that are observed after right-brain damage are associated with damage to the visuomotor control network, in particular with damage to the basal ganglia, frontal and parieto-occipital regions. On the other hand, clear neglect-specific deficits emerge when the action is off-line and not directly target-driven, thus requiring relational metrics or scene-based coordinates (as is the case for example in delayed and mirrored (anti-pointing) reaches). We review recent studies that support our argument that such deficits in off-line actions are associated with damage to occipito-temporal and parahippocampal cortex, perhaps as part of the ventral visual stream or areas where information from the two visual streams is combined. PMID- 21978833 TI - Neutralization of chemokine CXCL14 (BRAK) expression reduces CCl4 induced liver injury and steatosis in mice. AB - Using mouse gene expression microarray analysis, we earlier obtained dynamic profiles of whole genome expression in the CCl(4)-induced liver injury mouse model. CXCL14 expression was increased in the liver injury phase and returned to normal after liver regeneration suggesting its involvement in the liver injury or regeneration regulation. The role of CXCL14 in liver injury was investigated. The dynamic of CXCL14 transcription was analyzed in CCl(4)-induced mouse liver damage by qRT-PCR. Plasmid mediated CXCL14 overexpression and antibody neutralization of endogenous CXCL14 were used to demonstrate its effects and mechanisms on CCl(4) induced liver injury and acute liver failure. We showed that CXCL14 expression was immediately upregulated post CCl(4) injection with a dose-dependent response. CXCL14 over-expression aggravated CCl(4)-induced liver injuries, evidenced by enhanced acidophilic change and necrosis of hepatocyte, increased fat deposition in hepatocytes (P<0.01), and inhibited hepatocyte proliferation (P<0.01). On the contrary, anti-CXCL14 antibody treatment reduced the severity of CCL4-induced liver injuries Significant reductions in hepatic necrosis area (P<0.05), the liver fat deposition (P<0.01), and the lipid peroxidation measured by serum MDA (P<0.05) were observed. Importantly, the antibody treatment reduced the mouse mortality caused by CCl4-induced liver failure (P<0.05). The data suggest that CXCL14 and its receptor present potential targets for the treatment of liver diseases. PMID- 21978834 TI - Role of actin depolymerizing factor in the development of methamphetamine-induced place preference in mice. AB - The present study investigated role of actin depolymerizing factor (ADF) in methamphetamine-induced place preference using ADF mutant (ADFm) and wild-type mice (WT). Whereas methamphetamine developed dose-dependently place preference in wild-type mice, methamphetamine-induced place preference was significantly attenuated by ADF mutation. Moreover, the administration of phalloidin, an F actin stabilizer, dose-dependently inhibited methamphetamine-induced place preference. Methamphetamine-conditioning significantly increased the protein levels of ADF, cofilin, G-actin and F-actin in the limbic forebrain of both WT and ADFm, though the degree of enhancement of G- and F-actins by methamphetamine in ADFm was significantly smaller than in WT. Immunohistochemical study showed the co-localization of synaptophysin and tyrosine hydroxylase in WT and the potentiation of the immunoreactivity of these proteins by methamphetamine conditioning, whereas such potentiation was suppressed by ADF mutation. In addition, the protein levels of synaptophysin, post-synaptic density 95 (PSD95), and neuroligin1 significantly increased in the limbic forebrain of WT showing methamphetamine-induced place preference, but not in ADFm. These findings indicate that ADF play an important role in the development of methamphetamine induced place preference via regulation of actin dynamics. PMID- 21978835 TI - Hyperoside protects primary rat cortical neurons from neurotoxicity induced by amyloid beta-protein via the PI3K/Akt/Bad/Bcl(XL)-regulated mitochondrial apoptotic pathway. AB - Amyloid beta-protein (Abeta), which is deposited in neurons as neurofibrillary tangles, is known to exert cytotoxic effects by inducing mitochondrial dysfunction. Additionally, the PI3K/Akt-mediated interaction between Bad and Bcl(XL) plays an important role in maintaining mitochondrial integrity. However, the application of therapeutic drugs, especially natural products in Alzheimer's disease therapy via PI3K/Akt/Bad/Bcl(XL)-regulated mitochondrial apoptotic pathway has not aroused extensive attention. In the present study, we investigated the neuroprotective effects of hyperoside, a bioactive flavonoid compound from Hypericum perforatum, on Abeta(25-35)-induced primary cultured cortical neurons, and also examined the potential cellular signaling mechanism for Abeta detoxication. Our results showed that treatment with hyperoside significantly inhibited Abeta(25-35)-induced cytotoxicity and apoptosis by reversing Abeta-induced mitochondrial dysfunction, including mitochondrial membrane potential decrease, reactive oxygen species production, and mitochondrial release of cytochrome c. Further study indicated that hyperoside can activate the PI3K/Akt signaling pathway, resulting in inhibition of the interaction between Bad and Bcl(XL), without effects on the interaction between Bad and Bcl-2. Furthermore, hyperoside inhibited mitochondria-dependent downstream caspase-mediated apoptotic pathway, such as that involving caspase-9, caspase-3, and poly ADP-ribose polymerase (PARP). These results demonstrate that hyperoside can protect Abeta-induced primary cultured cortical neurons via PI3K/Akt/Bad/Bcl(XL)-regulated mitochondrial apoptotic pathway, and they raise the possibility that hyperoside could be developed into a clinically valuable treatment for Alzheimer's disease and other neuronal degenerative diseases associated with mitochondrial dysfunction. PMID- 21978836 TI - Synthesis and structure-activity relationship studies of 4-arylthiosemicarbazides as topoisomerase IV inhibitors with Gram-positive antibacterial activity. Search for molecular basis of antibacterial activity of thiosemicarbazides. AB - 1-(indol-2-carbonyl)-4-(4-nitrophenyl)-thiosemicarbazide was synthesized and antibacterial and type IIA topoisomerases (DNA gyrase and topoisomerase IV) activity was evaluated. It was found that it shows activity against Gram-positive bacteria with MICs of 50 MUg/mL and inhibitory action against topoisomerase IV with an IC(50) of 14 MUM. Although modification of its structure resulted in molecules with a lower biological profile, our observations strongly implicate that thiosemicarbazide derivatives participate in at least two different mechanisms of antibacterial activity; one is connected with the inhibition of topoisomerase IV, while the nature of the other cannot be elucidated from the limited data collected thus far. The differences in bioactivity further investigated by the molecular modeling approach and docking studies suggest that inhibitory activity of 4-arylthiosemicarbazides is connected with electronic structure rather than the geometry of the molecule. PMID- 21978837 TI - Synthesis of functionalized tetrasubstituted pyrazolyl heterocycles--a review. AB - Heterocyclic chemistry constitutes an essential branch of organic chemistry and heterocycles are widely known to display an array of biological properties. Pyrazoles represent key structural motifs in heterocyclic chemistry and are present in a large number of biologically active molecules relevant to the pharmaceutical and agrochemical industries. Compounds incorporating the pyrazolyl structural unit are being developed in a wide variety of therapeutic areas including CNS, metabolic diseases, and oncology. The current review summarizes recent advances in the synthesis of tetrasubstituted pyrazoles. The contents are discussed in five sections: (a) 1,3-dipolar cycloadditions, (b) related 1,3 dipolar cycloadditions, (c) condensations, (d) allenylphosphonates, and (e) synthesis of fused pyrazole containing heterocycles. PMID- 21978838 TI - Synthesis and antimycobacterial evaluation of 3a,4-dihydro-3H-indeno [1,2-c] pyrazole-2-carboxamide analogues. AB - In the present investigation, a series of 3a,4-dihydro-3H-indeno [1,2-c] pyrazole 2-carboxamide analogues were synthesized and were evaluated for antitubercular activity by two fold serial dilution technique. All the newly synthesized compounds showed low to good inhibitory activities against Mycobacterium tuberculosis H(37)Rv and multi-drug resistant M. tuberculosis (MDR-TB). 3-(4 fluorophenyl)-N-(4-chlorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno [1,2-c] pyrazole-2-carboxamide (4c) was found to be the most promising compound active against M. tuberculosis, H(37)Rv and MDR-TB with minimum inhibitory concentrations 0.83 MUM and 3.32 MUM respectively. PMID- 21978839 TI - Abductor pollicis longus hemitendon looping around the first intermetacarpal ligament as interposition following trapeziectomy: a one-year follow-up study. AB - BACKGROUND: Trapeziectomy and ligament reconstructions are favoured by surgeons concerned that telescoping of the thumb may reduce its function. However, theoretically ligamentoplasties are at risk to develop tendinosis or tendon rupture or trigger a complex regional pain syndrome type 1. HYPOTHESIS: Authors tested the looping of a slip from the abductor pollicis longus (APL) tendon around the first intermetacarpal ligament. They intended to use a surgical treatment which does not require bone tunnelling or looping around a tendon. Their results support the hypothesis that this new technique is a valid addition among treatments for carpometacarpal arthritis. PATIENTS AND METHODS: Forty-two patients were followed up to one year. Each patient had subjective assessment for: pain; function (DASH score); overall satisfaction. An objective assessment was used for: first web span angle; abduction and opposition; key pinch; grip strength. Tests were performed prior to surgery, then at three, six and 12 months. X-ray films were taken to monitor thumb height. RESULTS: A substantial improvement in all these parameters was measured in all patients. X-ray films showed the mantainance of a physiological heigth after one year. We recorded one complication of keloid and two of temporary dysesthesia but no case of tendinosis, delayed rupture, or CRPS 1. Mean operative time was 27 minutes. DISCUSSION: Simplification and search for a technique which avoids the looping around a tendon is why the authors undertook this study. Advantages are the small number of required steps, short time of surgery and comfortable postoperative rehab regimen for the patient. The technique provides a distal anchoring point (without bone tunnelling). It is quite respectful of anatomy and physiology, in minimizing the re-routing of functioning tendons. We propose it as an effective procedure both to expand the armamentarium for treating the thumb carpometacarpal joint osteoarthritis and/or to simplify the ligamentoplasties already in use. PMID- 21978840 TI - Evidence-based management of hyperglycemic emergencies in diabetes mellitus. AB - The hyperglycemic emergencies, diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are potentially fatal complications of uncontrolled diabetes mellitus. The incidence of DKA and the economic burden of its treatment continue to rise, but its associated mortality rate which was uniformly high has diminished remarkably over the years. This Improvement in outcome is largely due to better understanding of the pathogenesis of hyperglycemic emergencies and the application of evidence-based guidelines in the treatment of patients. In this article, we present a critical review of the evidence behind the recommendations that have resulted in the improved prognosis of patients with hyperglycemic crises. A succinct discussion of the pathophysiology and important etiological factors in DKA and HHS are provided as a prerequisite for understanding the rationale for the effective therapeutic maneuvers employed in these acute severe metabolic conditions. The evidence for the role of preventive measures in DKA and HHS is also discussed. The unanswered questions and future research needs are also highlighted. PMID- 21978841 TI - Jaw muscle fiber type distribution in Hawaiian gobioid stream fishes: histochemical correlations with feeding ecology and behavior. AB - Differences in fiber type distribution in the axial muscles of Hawaiian gobioid stream fishes have previously been linked to differences in locomotor performance, behavior, and diet across species. Using ATPase assays, we examined fiber types of the jaw opening sternohyoideus muscle across five species, as well as fiber types of three jaw closing muscles (adductor mandibulae A1, A2, and A3). The jaw muscles of some species of Hawaiian stream gobies contained substantial red fiber components. Some jaw muscles always had greater proportions of white muscle fibers than other jaw muscles, independent of species. In addition, comparing across species, the dietary generalists (Awaous guamensis and Stenogobius hawaiiensis) had a lower proportion of white muscle fibers in all jaw muscles than the dietary specialists (Lentipes concolor, Sicyopterus stimpsoni, and Eleotris sandwicensis). Among Hawaiian stream gobies, generalist diets may favor a wider range of muscle performance, provided by a mix of white and red muscle fibers, than is typical of dietary specialists, which may have a higher proportion of fast-twitch white fibers in jaw muscles to help meet the demands of rapid predatory strikes or feeding in fast-flowing habitats. PMID- 21978842 TI - Acoustic signals of baby black caimans. AB - In spite of the importance of crocodilian vocalizations for the understanding of the evolution of sound communication in Archosauria and due to the small number of experimental investigations, information concerning the vocal world of crocodilians is limited. By studying black caimans Melanosuchus niger in their natural habitat, here we supply the experimental evidence that juvenile crocodilians can use a graded sound system in order to elicit adapted behavioral responses from their mother and siblings. By analyzing the acoustic structure of calls emitted in two different situations ('undisturbed context', during which spontaneous calls of juvenile caimans were recorded without perturbing the group, and a simulated 'predator attack', during which calls were recorded while shaking juveniles) and by testing their biological relevance through playback experiments, we reveal the existence of two functionally different types of juvenile calls that produce a different response from the mother and other siblings. Young black caimans can thus modulate the structure of their vocalizations along an acoustic continuum as a function of the emission context. Playback experiments show that both mother and juveniles discriminate between these 'distress' and 'contact' calls. Acoustic communication is thus an important component mediating relationships within family groups in caimans as it is in birds, their archosaurian relatives. Although probably limited, the vocal repertoire of young crocodilians is capable of transmitting the information necessary for allowing siblings and mother to modulate their behavior. PMID- 21978843 TI - Xenotropic murine leukaemia virus-related virus (XMRV) does not cause chronic fatigue. AB - The xenotropic murine leukaemia virus-related virus (XMRV), a gammaretrovirus, was discovered in prostate cancer tumours by Virochip technology in 2006. It was subsequently detected in chronic fatigue patients in 2009. The association between XMRV and chronic fatigue has proved to be controversial. No study has confirmed these findings and many have refuted them. Here, we present the evidence for our contention that XMRV is not a human pathogen. PMID- 21978844 TI - Deviant ERP response to spoken non-words among adolescents exposed to cocaine in utero. AB - Concern for the impact of prenatal cocaine exposure (PCE) on human language development is based on observations of impaired performance on assessments of language skills in these children relative to non-exposed children. We investigated the effects of PCE on speech processing ability using event-related potentials (ERPs) among a sample of adolescents followed prospectively since birth. This study presents findings regarding cortical functioning in 107 prenatally cocaine-exposed (PCE) and 46 non-drug-exposed (NDE) 13-year-old adolescents. PCE and NDE groups differed in processing of auditorily presented non-words at very early sensory/phonemic processing components (N1/P2), in somewhat higher-level phonological processing components (N2), and in late high level linguistic/memory components (P600). These findings suggest that children with PCE have atypical neural responses to spoken language stimuli during low level phonological processing and at a later stage of processing of spoken stimuli. PMID- 21978846 TI - Differences among total and in vitro digestible phosphorus content of meat and milk products. AB - OBJECTIVE: Meat and milk products are important sources of dietary phosphorus (P) and protein. The use of P additives is common both in processed cheese and meat products. Measurement of in vitro digestible phosphorus (DP) content of foods may reflect absorbability of P. The objective of this study was to measure both total phosphorus (TP) and DP contents of selected meat and milk products and to compare amounts of TP and DP and the proportion of DP to TP among different foods. METHODS: TP and DP contents of 21 meat and milk products were measured by inductively coupled plasma optical emission spectrometry (ICP-OES). In DP analysis, samples were digested enzymatically, in principle, in the same way as in the alimentary canal before the analyses. The most popular national brands of meat and milk products were chosen for analysis. RESULTS: The highest TP and DP contents were found in processed and hard cheeses; the lowest, in milk and cottage cheese. TP and DP contents in sausages and cold cuts were lower than those in cheeses. Chicken, pork, beef, and rainbow trout contained similar amounts of TP, but slightly more variation was found in their DP contents. CONCLUSIONS: Foods containing P additives have a high content of DP. Our study confirms that cottage cheese and unenhanced meats are better choices than processed or hard cheeses, sausages, and cold cuts for chronic kidney disease patients, based on their lower P-to-protein ratios and sodium contents. The results support previous findings of better P absorbability in foods of animal origin than in, for example, legumes. PMID- 21978845 TI - Identifying bilingual semantic neural representations across languages. AB - The goal of the study was to identify the neural representation of a noun's meaning in one language based on the neural representation of that same noun in another language. Machine learning methods were used to train classifiers to identify which individual noun bilingual participants were thinking about in one language based solely on their brain activation in the other language. The study shows reliable (p<.05) pattern-based classification accuracies for the classification of brain activity for nouns across languages. It also shows that the stable voxels used to classify the brain activation were located in areas associated with encoding information about semantic dimensions of the words in the study. The identification of the semantic trace of individual nouns from the pattern of cortical activity demonstrates the existence of a multi-voxel pattern of activation across the cortex for a single noun common to both languages in bilinguals. PMID- 21978847 TI - Viability of common wine spoilage organisms after exposure to high power ultrasonics. AB - Microbial spoilage of wine can lead to significant economic loss. At present sulfur dioxide is the main additive to juice/must/wine to prevent and control microbial spoilage. As an alternative, or complement to SO(2), high power ultrasonics (HPU) may be used to control microbes. Several wine spoilage yeasts and bacteria were treated with HPU in saline (0.9% w/v NaCl), juice and red wine to assess their susceptibility to HPU. Significant killing was seen across several yeasts and bacteria commonly associated with winemaking and wine spoilage. In general the viability of yeast was more affected than that of bacteria. PMID- 21978848 TI - The effects of fasudil on the permeability of the rat blood-brain barrier and blood-spinal cord barrier following experimental autoimmune encephalomyelitis. AB - Dysfunction of the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) is a primary characteristic of multiple sclerosis (MS). We evaluated the protective effects of fasudil, a selective ROCK inhibitor, in a model of experimental autoimmune encephalomyelitis (EAE) that was induced by guinea-pig spinal cord. In addition, we studied the effects of fasudil on BBB and BSCB permeability. We found that fasudil partly alleviated EAE-dependent damage by decreasing BBB and BSCB permeability. These results provide rationale for the development of selective inhibitors of Rho kinase as a novel therapy for MS. PMID- 21978849 TI - Definitions and classification of work-related asthma. AB - The workplace can trigger or induce asthma and cause the onset of different types of work-related asthma (WRA). Based on current knowledge of clinical features, pathophysiologic mechanisms, and evidence supporting a causal relationship, the following conditions should be distinguished in the spectrum of WRA: (1) immunologic occupational asthma (OA), (2) nonimmunologic OA, (3) work-exacerbated asthma, and (4) variant syndromes, including eosinophilic bronchitis, potroom asthma, and asthmalike disorders caused by organic dusts. The rationale, issues, and controversies relating to this approach are critically reviewed to stimulate the development of a consensus on operational definitions of the various phenotypes of WRA. PMID- 21978850 TI - The epidemiology of work-related asthma. AB - Much has been learned from epidemiologic studies conducted in the past 4 decades that can be directly applied to the management of workers affected with occupational asthma. Studies have provided information about host factors, environmental exposure, and occupational agents posing the highest risks for development of severe irreversible airway obstruction and asthma disability. Investigators have developed methods for screening workers at risk and novel interventions that may prevent new cases among exposed worker populations. Less is known about the natural history and chronic morbidity associated with work aggravated asthma and irritant-induced asthma syndromes; more studies are needed in at-risk worker populations. PMID- 21978851 TI - Old and new causes of occupational asthma. AB - International reviews suggest that the median proportion of adult cases of asthma attributable to occupational exposure is between 10% and 15%. Therefore, it is essential that clinicians have a broad knowledge of the various causes associated with occupational asthma. Occupational asthmagens are categorized as low molecular-weight (LMW, <=1000 kd) and high-molecular-weight (HMW, >=1000 kd) antigens. The purpose of this article is to review the most common representative LMW and HMW causes of occupational asthma over the past 70 years, with specific emphasis on newer causes reported over the past 5 years. PMID- 21978853 TI - Clinical assessment of occupational asthma and its differential diagnosis. AB - Occupational asthma (OA) is defined as asthma caused by sources and conditions attributable to a particular occupational environment and not to stimuli encountered outside the workplace. Two types of OA are distinguished based on their appearance after a latency period or not. The most frequent type appears after a latency period leading to sensitization; the clinical assessment of this type of OA is the topic of this review. The differential diagnosis of OA is also reviewed, including work-exacerbated asthma, eosinophilic bronchitis, hyperventilation syndrome, vocal cord dysfunction, bronchiolitis, and other causes of dyspnea or cough. PMID- 21978854 TI - Work-related asthma: a case-based approach to management. AB - The management of work-related asthma has some differences from management of other asthma. Components of management include not only making as accurate a diagnosis as possible, identifying the causative agent or triggers at work, and managing the asthma with pharmacologic treatment as for other patients with asthma, but also advising on the appropriate work changes that may be needed, assisting the worker with appropriate compensation claims, and supporting protective measures for coworkers. This article discusses the approaches that may be taken for patients with different forms of work-related asthma. PMID- 21978852 TI - Pathogenesis and disease mechanisms of occupational asthma. AB - Occupational asthma (OA) is one of the most common forms of work-related lung disease in all industrialized nations. The clinical management of patients with OA depends on an understanding of the multifactorial pathogenetic mechanisms that can contribute to this disease. This article discusses the various immunologic and nonimmunologic mechanisms and genetic susceptibility factors that drive the inflammatory processes of OA. PMID- 21978855 TI - Irritant-induced airway disorders. AB - Thousands of persons experience accidental high-level irritant exposures each year but most recover and few die. Irritants function differently than allergens because their actions proceed nonspecifically and by nonimmunologic mechanisms. For some individuals, the consequence of a single massive exposure to an irritant, gas, vapor or fume is persistent airway hyperresponsiveness and the clinical picture of asthma, referred to as reactive airways dysfunction syndrome (RADS). Repeated irritant exposures may lead to chronic cough and continual airway hyperresponsiveness. Cases of asthma attributed to repeated irritant exposures may be the result of genetic and/or host factors. PMID- 21978856 TI - Hypersensitivity pneumonitis and related conditions in the work environment. AB - Hypersensitivity pneumonitis can occur from a wide variety of occupational exposures. Although uncommon and difficult to recognize, through a detailed work exposure history, physical examination, radiography, pulmonary function studies, and selected laboratory studies using sera and bronchoalveolar lavage fluid, workers can be identified early to effect avoidance of the antigen and institute pharmacologic therapy, if necessary. A lung biopsy may be necessary to rule out other interstitial lung diseases. Despite the varied organic antigen triggers, the presentation is similar with acute, subacute, or chronic forms. Systemic corticosteroids are the only reliable pharmacologic treatment but do not alter the long-term outcome. PMID- 21978857 TI - Occupational rhinitis. AB - Work-related rhinitis, which includes work-exacerbated rhinitis and occupational rhinoconjunctivitis (OR), is two to three times more common than occupational asthma. High molecular weight proteins and low molecular weight chemicals have been implicated as causes of OR. The diagnosis of work-related rhinitis is established based on occupational history and documentation of immunoglobulin E (IgE) mediated sensitization to the causative agent if possible. Management of work-related rhinitis is similar to that of other causes of rhinitis and includes elimination or reduction of exposure to causative agents combined with pharmacotherapy. If allergens are commercially available, allergen immunotherapy can be considered. PMID- 21978858 TI - When the workplace air makes me wheeze--occupational asthma. PMID- 21978859 TI - Occupational asthma. Preface. PMID- 21978860 TI - The influence of personal dispositional factors and organizational resources on workplace violence, burnout, and health outcomes in new graduate nurses: a cross sectional study. AB - BACKGROUND: The alarmingly high rate of illness-related absenteeism among nurses and recent reports of workplace violence and burnout are problematic for both the current workforce shortage and the recruitment and retention of new nurses. OBJECTIVES: To test a model derived from Leiter and Maslach's (2004) Six Areas of Worklife Model linking workplace factors (six areas of worklife, experiences of bullying and burnout) and a personal dispositional factor (psychological capital) to new graduates mental and physical health in their first year of practice. METHODS: A cross-sectional survey design was utilized to survey 165 Ontario nurses with one year or less experience in nursing. Participants completed measures of nurses' work environment quality, psychological capital, bullying exposure, burnout, and physical and mental health. Structural equation modelling was used to test the hypothesized model. RESULTS: The fit indices suggested a reasonably adequate fit of the data to the hypothesized model (chi2=27.75, df=12, CFI=.97, IFI=.97, RMSEA=.09), however an additional direct path from psychological capital to emotional exhaustion substantially improved the model fit (chi2=17.94, df=11, CFI=.99, IFI=.99, RMSEA=.06). Increased psychological capital positively influenced nurses' perceived person-job fit, which in turn was negatively related to bullying exposure and emotional exhaustion, and ultimately influenced their physical and mental health. CONCLUSIONS: The findings suggest that psychological capital and perceived person-job fit are key variables in new graduate nurses' worklife, which may contribute to decreased nurses' burnout and increased physical and mental well-being. The results support an expanded conceptualization of the areas of worklife model. PMID- 21978861 TI - Protocol for a randomised controlled trial of nasal high flow oxygen therapy compared to standard care in patients following cardiac surgery: the HOT-AS study. AB - BACKGROUND: Postoperative respiratory complications following cardiac surgery may increase morbidity, mortality and length of stay. Non-invasive respiratory support therapies can be used prophylactically or curatively to reduce respiratory complications. One system, nasal high flow oxygen therapy, is in use in many intensive care units (ICUs) however there is a lack of information regarding its clinical utility and efficacy. OBJECTIVES: This paper outlines the study protocol and methodology for a study designed to determine if the prophylactic use of nasal high flow oxygen therapy can improve pulmonary function in patients following cardiac surgery. METHODS/DESIGN: A prospective randomised controlled trial will be conducted of adult patients scheduled for cardiac surgery and admitted to the Cardiothoracic Intensive Care Unit of a tertiary hospital. Study participants will be assigned to receive either nasal high flow or standard oxygen therapy (oxygen therapy at 2-4 L/min via either simple facemask or nasal cannulae) at extubation. The primary outcome measure is improved pulmonary function demonstrated by SpO2/FiO2 ratio >445 on post operative day 3. Secondary outcome measures include atelectasis score on chest X ray; spirometry; readmission to ICU for respiratory causes; ICU and hospital length of stay; mortality and incidence of respiratory complications at day 28; oxygenation variables; use of adjunctive respiratory support therapies; escalation of respiratory support; adverse events and patient comfort during administration of oxygen therapy. SAMPLE SIZE: It was calculated that 340 patients will be required--170 per arm of study--to give a 90% power to detect a 15% treatment effect. RESULTS: This study started recruiting in March 2011. It is anticipated that enrollment will be complete in April 2012 and results available towards the end of 2012. CONCLUSION: This study will provide evidence of any benefits in the use of prophylactic nasal high flow therapy in post-operative cardiac surgical patients. TRIAL REGISTRATION: This trial is registered with the Australian New Zealand Clinical Trials Registry www.anzctr.org.au (ACTRN12610000973011). PMID- 21978862 TI - Preconceptional paternal glycidamide exposure affects embryonic gene expression: single embryo gene expression study following in vitro fertilization. AB - Recognition of early determinants of disease onset has sparked an interest in paternally transmitted factors and their impact on the developing embryo. Acrylamide (AA), a widely distributed xenobiotic compound, is converted to its active metabolite glycidamide (GA) by the CYP2E1 enzyme. Based on its capacity to induce dominant lethal mutations, we hypothesized that paternal GA exposure would have a negative impact on embryonic genome activation, via GA-DNA and protamine adducts persisting in the fertilizing sperm. Using a combination of in vitro fertilization (IVF) techniques and RT-qPCR single embryo gene expression (SEGE), we studied the expression of key DNA repair genes and genes important for embryo development, at the 1-, 2-, 4- and 8-cell stage of the developing mouse embryo. Compared to controls paternal GA-exposure gave rise to an altered pattern of embryonic gene expression, with an initial reduced expression at early stages followed by increased expression at the 8-cell stage. PMID- 21978863 TI - Zebrafish eleutheroembryos as an alternative system for screening chemicals disrupting the mammalian thyroid gland morphogenesis and function. AB - The importance and irreversibility of the effects of thyroid hormone deficiency on human brain development highlight the importance of identifying environmental agents that interfere with thyroid gland morphogenesis and function. Zebrafish eleutheroembryos are currently used by many pharmaceutical companies in drug discovery as a vertebrate model, not subjected to regulations for animal experiments, that provides an intermediate step between in vitro and rodent assay. The mechanisms of zebrafish thyroid development are generally comparable to those in humans, and moreover, molecular and functional studies of zebrafish thyroid follicles have demonstrated a high degree of conservation with upper vertebrates, opening up the possibility of designing alternative methods for screening individual chemicals and mixtures that impairing thyroid gland morphogenesis and/or function. Analysis of the intrafollicular thyroxine-content of zebrafish larvae exposed to potential disruptors has proved to be a reliable, physiologically relevant endpoint to estimate effects of chemicals on the mammalian thyroid gland. PMID- 21978865 TI - Aryl hydrocarbon receptor-mediated Cyp1a1 expression is modulated in a CLOCK dependent circadian manner. AB - The expression of genes involved in xenobiotic detoxification is under the control of the circadian clock. The aryl hydrocarbon receptor (AhR) is one of the transcription factors responsible for the induction of detoxification enzymes in response to xenobiotic toxins, and the expression of AhR has been suggested to be regulated by a circadian oscillator. In this study, we investigated whether toxin mediated activation of the AhR signaling pathway was modulated by CLOCK protein, a key component of the mammalian circadian clock. The expression of AhR and its DNA binding ability in the lungs of wild-type mice showed significant 24-h oscillation. Clock mutant (Clk/Clk) mice, producing CLOCK protein deficient in transcriptional activity, failed to show significant oscillation in the expression of AhR. The mRNA levels of AhR in the lungs of Clk/Clk mice were significantly lower than in wild-type mice. A single intraperitoneal injection of benzo[alpha]pyrene, a ligand of AhR, induced the expression of Cyp1a1 in the lungs of wild-type mice, but the induction varied depending on the benzo[alpha]pyrene injection time. The dosing time-dependency of benzo[alpha]pyrene-induced Cyp1a1 expression was also modulated by Clock gene mutation. These findings suggest that CLOCK protein affects the toxin-induced expression of detoxification enzymes through modulating the activity of AhR. Our present findings provide a molecular link between the circadian clock and xenobiotic detoxification. PMID- 21978864 TI - Neuronal action on the developing blood vessel pattern. AB - The nervous system relies on a highly specialized network of blood vessels for development and neuronal survival. Recent evidence suggests that both the central and peripheral nervous systems (CNS and PNS) employ multiple mechanisms to shape the vascular tree to meet its specific metabolic demands, such as promoting nerve artery alignment in the PNS or the development the blood brain barrier in the CNS. In this article we discuss how the nervous system directly influences blood vessel patterning resulting in neuro-vascular congruence that is maintained throughout development and in the adult. PMID- 21978866 TI - Multifunctional drugs as novel antidotes for organophosphates' poisoning. AB - Some organophosphorus compounds (OPs) are nerve agents that continue to concern military personnel and civilians as potential battlefield and terrorist threats. Additionally, OPs are used in agriculture where they are associated with numerous cases of intentional and accidental misuse. These toxicants induce an array of deleterious effects including respiratory distress, convulsions and ultimately death. A mechanism involving a rapid and potent inhibition of peripheral and central cholinesterases leading to a massive buildup of acetylcholine in synaptic clefts was suggested as the underlying trigger of the toxic events. Indeed, therapy comprised of an acetylcholinesterase reactivator (i.e., oxime) and a cholinergic antagonist (e.g., atropine) is the accepted major paradigm for protection. This approach yields a remarkable survival rate but fails to prevent neurological and behavioral deficits. Extensive research revealed a complex picture consisting of an early activation of several neurotransmitter systems, in which the glutamatergic plays a pivotal role., Data accumulated in recent years support the concept that multi-targeting of pathways including glutamatergic and cholinergic circuits is required for an effective treatment. Drugs that demonstrate the ability to interact with several systems (e.g., caramiphen) were found to afford a superior protection against OPs as compared to specific antimuscarinic ligands (e.g., scopolamine). Compounds that potently block muscarinic receptors, interact with the NMDA ion channel and in addition are able to modulate sigma(1) sites and/or GABAergic transmission seem to represent the emerging backbone for novel antidotes against OP poisoning. Several multifunctional drugs are already used for complex diseases e.g., cancer and depression. PMID- 21978868 TI - Associations between DNA methylation of a glucocorticoid receptor promoter and acute stress responses in a large healthy adult population are largely explained by lifestyle and educational differences. AB - BACKGROUND: Glucocorticoids are the key regulators of the biological stress response and act by binding to glucocorticoid receptors (GR). Expression of GR is altered by DNA methylation. Methylation patterns in GR promoters have been shown to be highly variable between individuals, but little is known about the functional consequences of this variation for the acute stress response. The present study investigated associations between methylation status of the GR 1-C promoter and cortisol, cardiovascular and perceived stress responses to a psychosocial stress protocol in a large healthy adult population. METHODS: A total of 725 overall healthy men and women, aged 55-60 years, participated in a standardized psychosocial stress protocol consisting of three different stressors. At different stages during the stress protocol, salivary cortisol levels, continuous blood pressure and heart rate (HR) levels as well as perceived stress were measured. Stress reactivity was calculated as the increase between basal and peak measurements. Methylation status of the GR 1-C promoter was assessed in DNA isolated from peripheral blood samples using a methylation sensitive PCR assay for 675 of the 725 participants. RESULTS: A decrease in methylation of the GR 1-C promoter was associated with a decrease in stress reactivity as indicated by lower cortisol and lower HR reactivity. A 1% decrease in GR 1-C methylation corresponded with a cortisol decrease by 0.14% (95% CI: 0.03-0.25, p=0.02) and an HR decrease by 0.10 bpm (0.03-0.16, p=0.003). Adjusting for sex, lifestyle and education largely abolished these associations. A decrease in methylation of the GR 1-C promoter was also associated with an increase in stress perception as indicated by higher perceived stress (0.03 points [0.00 0.06, p=0.05]), lower perceived performance (-0.03 points [-0.05 to -0.01], p=0.02), and lower perceived control (-0.03 points [-0.05 to 0.00], p=0.04). After adjusting for sex and educational level the associations were no longer statistically significant. GR 1-C methylation status was not associated with blood pressure responses to the stress protocol. DISCUSSION: Although effects were small, variation in methylation status in the GR 1-C promoter was associated with physical and perceived acute stress responses. Interestingly, these associations could largely be explained by differences in lifestyle and education. PMID- 21978867 TI - Comprehension of insincere communication in neurodegenerative disease: lies, sarcasm, and theory of mind. AB - Comprehension of insincere communication is an important aspect of social cognition requiring visual perspective taking, emotion reading, and understanding others' thoughts, opinions, and intentions. Someone who is lying intends to hide their insincerity from the listener, while a sarcastic speaker wants the listener to recognize they are speaking insincerely. We investigated whether face-to-face testing of comprehending insincere communication would effectively discriminate among neurodegenerative disease patients with different patterns of real-life social deficits. We examined ability to comprehend lies and sarcasm from a third person perspective, using contextual cues, in 102 patients with one of four neurodegenerative diseases (behavioral variant frontotemporal dementia [bvFTD], Alzheimer's disease [AD], progressive supranuclear palsy [PSP], and vascular cognitive impairment) and 77 healthy older adults (normal controls--NCs). Participants answered questions about videos depicting social interactions involving deceptive, sarcastic, or sincere speech using The Awareness of Social Inference Test. All subjects equally understood sincere remarks, but bvFTD patients displayed impaired comprehension of lies and sarcasm compared with NCs. In other groups, impairment was not disease-specific but was proportionate to general cognitive impairment. Analysis of the task components revealed that only bvFTD patients were impaired on perspective taking and emotion reading elements and that both bvFTD and PSP patients had impaired ability to represent others' opinions and intentions (i.e., theory of mind). Test performance correlated with informants' ratings of subjects' empathy, perspective taking and neuropsychiatric symptoms in everyday life. Comprehending insincere communication is complex and requires multiple cognitive and emotional processes vulnerable across neurodegenerative diseases. However, bvFTD patients show uniquely focal and severe impairments at every level of theory of mind and emotion reading, leading to an inability to identify obvious examples of deception and sarcasm. This is consistent with studies suggesting this disease targets a specific neural network necessary for perceiving social salience and predicting negative social outcomes. PMID- 21978869 TI - Genetic and hormonal sensitivity to threat: testing a serotonin transporter genotype * testosterone interaction. AB - BACKGROUND: Striking parallels are observed when comparing the literature on the 5-HTTLPR of the serotonin transporter gene (SLC6A4) to the testosterone (T) literature on measures of stress reactivity and neural activity. Short (S) allele carriers and individuals higher in testosterone levels show exaggerated stress responses, amygdala hyperactivity, and reduction of amygdala-prefrontal cortex coupling when exposed to threat. METHODS: Three studies tested the hypothesis that higher T, S carriers would show increased cortisol responses to threat. RESULTS: Supporting the hypothesis, a T * 5-HTTLPR interaction was obtained across all studies. Threats to status via social exclusion (Study 1), cognitive/perceptual failure (Study 2), and physical competence (Study 3) all produced elevated cortisol levels in S carriers with higher T levels. An unexpected result was that 5-HTTLPR long (L) allele homozygotes with higher T showed lower cortisol levels in response to threat-a pattern of response that closely parallels that reported for psychopathic individuals. Finally, combining effect sizes across studies showed that the likelihood that these effects were due to Type 1 errors was quite low. CONCLUSIONS: What emerges from these studies is a novel yet reliable, and synergistic relationship between 5-HTTLPR genotype and testosterone on stress reactivity, possibly conferring vulnerability for multiple neuropsychiatric disorders. PMID- 21978870 TI - The progression of a transcatheter aortic valve program: a decision analysis of more than 680 patient referrals. AB - BACKGROUND: A ground-breaking, US Food and Drug Administration clinical trial for the treatment of critical aortic stenosis commenced at our institution in November 2007 with our first transcatheter aortic valve repair (TAVR). This novel procedure created a new treatment option for high-risk patients with aortic stenosis. Although the pivotal trial completed enrollment in 2009, continued access was implemented by the Food and Drug Administration in response to an unprecedented demand for this new procedure by patients and physicians. This is an overview of one site's management strategy for patient referrals. METHODS: Patients underwent evaluation with a comprehensive assessment in a multidisciplinary transcatheter aortic valve clinic. All screened patients were classified as either traditional open surgical candidates or nonsurgical candidates. Major exclusions for open procedures included low Society of Thoracic Surgeons score, coronary artery disease, and other valvular disease. Major exclusions of nonsurgical candidates resulted from physician discretion or multiple comorbidities such as renal failure, significant liver or lung disease, and progressive cancer. A third group of patients was excluded because of inadequate femoral access. RESULTS: From November 2007 to November 2010, 681 patients were referred for evaluation, including 578 screened patients and 103 patients whose evaluation was pending. During the screening process, 82 patients died (12%). Among 343 patients who did not qualify for enrollment (50%), 108 received open surgical intervention and 235 were nonsurgical candidates; 35 of these patients underwent balloon aortic valvuloplasty. A total of 153 patients were enrolled in the TAVR trial. CONCLUSIONS: With the availability of a novel treatment option for aortic stenosis in high-risk patients, institutions offering these alternative methods will be forced to reevaluate patient management. A careful strategy that includes multidisciplinary evaluation is crucial in order to have a successful transcatheter aortic valve program. PMID- 21978871 TI - Perioperative management of patients on clopidogrel (Plavix) undergoing major lung resection. AB - BACKGROUND: Management of patients requiring antiplatelet therapy with clopidogrel (Plavix) and major lung resection must balance the risks of bleeding and cardiovascular events. We reviewed our experience with patients treated with clopidogrel perioperatively to examine outcomes, including results of a new strategy for high-risk patients. METHODS: Patients who underwent major lung resection and received perioperative clopidogrel between January 2005 and September 2010 were reviewed. Initially, clopidogrel management consisted of discontinuation approximately 5 days before surgery and resumption immediately after surgery. After July 2010, high-risk patients (drug-eluting coronary stent placement within prior year or previous coronary event after clopidogrel discontinuation) were admitted 2 to 3 days preoperatively and bridged with the intravenous glycoprotein IIb/IIIa receptor inhibitor eptifibatide (Integrilin) according to a multidisciplinary cardiology/anesthesiology/thoracic surgery protocol. Outcomes were compared with control patients (matched for preoperative risk factors and extent of pulmonary resection) who did not receive perioperative clopidogrel. RESULTS: Fifty-four patients who had major lung resection between January 2005 and September 2010 and received clopidogrel perioperatively were matched with 108 control subjects. Both groups had similar mortality, postoperative length of stay, and no differences in the rates of perioperative transfusions, reoperations for bleeding, myocardial infarctions, and strokes. Seven of the 54 clopidogrel patients were admitted preoperatively for an eptifibatide bridge. Two of these patients received perioperative transfusions, but there were no deaths, reoperations, myocardial infarctions, or stroke. CONCLUSIONS: Patients taking clopidogrel can safely undergo major lung resection. Treatment with an eptifibatide bridge may minimize the risk of cardiovascular events in higher risk patients. PMID- 21978872 TI - Outcomes after conversion in the Veterans Affairs randomized on versus off bypass trial. AB - BACKGROUND: The Randomized On versus Off Bypass trial reported conversion of 12.4% (n = 137) off-pump coronary artery bypass (OPCAB) patients and 3.6% (n = 40) on-pump cardiopulmonary bypass (CPB) patients. This paper explored outcomes after conversions. METHODS: Elective and urgent CABG patients (n = 2,203) at 18 sites were studied. Randomization within 54 participating surgeons occurred preoperatively, after which conversion occurred if clinically indicated. Conversion reasons and outcomes were captured prospectively with additional details retrospectively extracted from patient records by a core clinical group. RESULTS: Conversion rates varied considerably across participating surgeons. Converted OPCAB patients had more right coronary disease and coronary targets less than 1.5 mm. Conversions were elective in 49.3% of cases, urgent in 27.2%, or emergent in 23.5%. Elective conversions were mainly for poor exposure intramyocardial vessel (35.8%). Urgent and emergent conversions were usually for hemodynamic instability (89.2% and 75.0%, respectively). Compared with CPB and OPCAB patients, OPCAB-converted patients had more 30-day complications and deaths (composite outcome rate of 5.7% and 5.5% vs 17.5% respectively, p < 0.001). Thirty-day outcomes for OPCAB-converted patients trended worse for emergent versus elective conversions (31.3% vs 13.4%, respectively, p = 0.05). One-year composite outcome rate (death, nonfatal myocardial infarction or revascularization) in OPCAB-converted patients was worse than in CPB patients (13.5% vs 7.1%, p = 0.02), but similar to OPCAB-nonconverted (9.4%). CONCLUSIONS: The OPCAB patients requiring conversion had worse 30-day and 1-year outcomes. The OPCAB patients with right coronary artery disease or small targets were more often converted. The 30-day composite outcome trended worst for emergent OPCAB conversions. PMID- 21978873 TI - Cardiac surgery in Jehovah's Witness patients: ten-year experience. AB - BACKGROUND: Cardiac surgery in Jehovah's Witnesses poses unique challenges. We have developed a comprehensive multimodality program for these patients and have obtained excellent results. METHODS: Ninety-one Jehovah's Witness patients underwent cardiac surgery between 2000 and 2010. Preoperative, intraoperative, and postoperative considerations in the conduct of bloodless surgery in the Jehovah's Witness population are discussed. Mortality for isolated coronary artery bypass graft surgery and isolated aortic valve replacement was compared with predicted mortality from The Society of Thoracic Surgeons (STS) risk models. Perioperative outcomes were stratified by urgent and elective status of operations. RESULTS: Mean age was 65+/-12.4 years. Comorbid conditions included hypertension (84.6%), diabetes mellitus (48.4%), previous myocardial infarction (23.1%), chronic lung disease (38.5%), peripheral vascular disease (20.9%), and renal failure (11%). In-hospital mortality was 5.5% (n=5). Mortality for isolated coronary artery bypass graft surgery and isolated aortic valve replacement was 2.2% (observed to expected ratio=1.05, 95% confidence interval: 0 to 3.02) and 5.6% (observed to expected=1.46, 95% confidence interval: 0 to 3.76), respectively. Other complications included reoperation (all=8.8%, cardiac=2.2%), sepsis (2.2%), sternal wound infection (1.1%), transient ischemic attack (1.1%), renal failure requiring dialysis (1.1%), and prolonged ventilation (18.7%). Major complication rates were not significantly different between the elective group and the urgent group. CONCLUSIONS: Bloodless cardiac surgery in Jehovah's Witness patients can be performed with excellent outcomes in both elective and urgent situations. Mortality rates for isolated coronary artery bypass graft surgery and isolated aortic valve replacement are within the expected 95% confidence intervals of STS predicted mortality. PMID- 21978874 TI - New-onset postoperative atrial fibrillation predicts late mortality after mitral valve surgery. AB - BACKGROUND: New-onset postoperative atrial fibrillation (POAF) is a common rhythm disturbance after mitral valve surgery. In this study we investigated the independent effect of POAF on early and late mortality after mitral valve surgery. METHODS: Data of patients who consecutively underwent mitral valve surgery with or without concomitant coronary or tricuspid valve surgery between January 2003 and June 2010 were prospectively collected. The study included 856 patients with preoperative sinus rhythm, and no history of atrial fibrillation. Logistic regression and Cox proportional hazard analyses were performed to investigate independent predictors of early and late mortality. Propensity score adjustment was performed to reduce the effect of confounders. RESULTS: The median follow-up was 3.1 years (range, 0 to 7.4 years). The POAF was documented in 361 patients (42%). Early mortality did not differ in patients with and without POAF (p = 0.93). Postoperative atrial fibrillation was not identified as predictor for early mortality. Late survival was worse in patients with POAF (log-rank, p < 0.001). Multivariate and propensity score adjusted Cox proportional hazard analyses demonstrated that POAF was an independent predictor for late mortality with hazard ratios of 2.09 and 1.61 (p = 0.001 and p = 0.033, respectively). CONCLUSIONS: Postoperative atrial fibrillation is an independent predictor for late all-cause mortality after mitral valve surgery but not for early all-cause mortality. PMID- 21978875 TI - Thoracoscopic thymectomy for myasthenia gravis with and without thymoma: a single center experience. AB - BACKGROUND: The treatment of patients with myasthenia gravis (MG) may include thymectomy. The objective of this study was to analyze the outcome of video assisted thoracoscopic surgical (VATS) extended thymectomy and to compare characteristics of patients with MG with and without thymoma. METHODS: Between 2002 and 2009, 247 patients with MG underwent VATS thymectomy in our department and were subdivided into 2 groups: MG without thymoma (n=176) and MG with thymoma (n=71). Complete stable remission (CSR) was the primary endpoint for efficacy. RESULTS: There were no intraoperative deaths and 4 cases required conversion to median sternotomy. There was a significant difference between the 2 groups regarding preoperative and postoperative myasthenic crisis. Two hundred nineteen patients were followed for 4 months to 9 years: 152 had thymoma and 67 did not have thymoma. The cumulative probabilities of reaching CSR were 37.5% in patients with MG without thymoma and 28.3% in patients with thymoma, respectively. Forty months after surgery there was no significant difference in CSR between the 2 groups. Two years after surgery, 30 patients without thymoma achieved CSR and disease was exacerbated in 2 patients after CSR had been achieved. Ten patients with thymoma achieved CSR, and exacerbation occurred in 5 patients with thymoma. Two patients without thymoma died of myasthenic crisis, whereas 3 of 4 patients with thymoma died of myasthenic crisis, and 1 death was attributable to recurrent disease. CONCLUSIONS: Video-assisted thoracoscopic surgery thymectomy can produce a satisfactory long-term result. MG with thymoma seems more severe and its prognosis after thymectomy is not as optimistic as that of MG without thymoma. Special perioperative attention should be paid to patients with MG and thymoma to decrease the possibility of postoperative myasthenic crisis and reduce postoperative death. PMID- 21978876 TI - Hemoglobin-based oxygen carriers for hemorrhagic shock. AB - Hemorrhagic shock is a pathologic state in which intravascular volume and tissue oxygen delivery are impaired, leading to circulatory collapse and cellular ischemia. Resuscitation with hemoglobin-based oxygen carriers (HBOCs) is appealing in that their use can both restore intravascular volume and tissue oxygenation, without the limitations in supply and immunomodulatory effects of packed red blood cells. However, the development of safe and effective agents has been elusive. In this article, we briefly discuss the major limitations of traditional resuscitative fluids which have driven the continued interest in HBOCs. We then review the history of early HBOC development and the modern understanding of their mechanisms of toxicity, which has informed the rational design of second-generation agents. Finally, we provide an overview of these second-generation HBOCs that are under active investigation or have recently completed phase 3 clinical trials. PMID- 21978877 TI - Ultrasound measurements of the saphenous vein in the pediatric emergency department population with comparison to i.v. catheter size. AB - BACKGROUND: Saphenous vein cutdown is a rare venous access procedure. Ultrasound (US) can assist with many vascular access procedures. OBJECTIVES: Our objective was to identify the saphenous veins (SVs) using US in pediatric emergency department (ED) patients, and to determine if the SV size allows for potential cannulation by different standard-size intravenous (i.v.) catheters. METHODS: This study was a prospective, observational convenience sample of 60 pediatric patients at an urban, regional referral pediatric ED. Inclusion criteria were children ages 1 through 12 years categorized into four age groups: 1-<2, 2-4, 5 7, and 8-12 years, with informed consent and assent. Investigators performed US examination using a 10-MHz multi-frequency transducer to identify the SV on both legs and measure the SV in short-axis view. The US measurements were then used to calculate the SV areas. Diameters of typical pediatric gauge (G) catheters (24G, 22G, 20G, 18G) were used to calculate catheter areas. RESULTS: Sixty patients were enrolled, with five SVs unable to be measured in 4 patients (1 patient with both SVs). For the remaining 115 (96%) SVs available for further analysis, the median age was 4 years (interquartile range [IQR] 2) and median weight was 22.7 kg (IQR 14.5). Mean area (mm(2)) of the right SV was 2.85 +/- 1.9 and for the left SV, 2.88 +/- 1.8. For our study group, the compatibility rates of different size i.v. catheters to fit the measured SV areas were as follows: 24G = 100%, 22G = 100%, 20G = 97.3%, and 18G =86.1%. CONCLUSIONS: US can localize the SV in pediatric ED patients. US size of the SV in various pediatric age ranges suggests that the SV may be a potential US venous access site with multiple-size i.v. catheters up to 18G. PMID- 21978878 TI - Confirmed glyburide poisoning from ingestion of "street Valium". AB - BACKGROUND: Pharmaceuticals with little to no abuse potential are often sold surreptitiously as drugs of abuse on the street. Anecdotally, sulfonylureas are suspected to be commonly sold as "street Valium." CASE REPORTS: Two patients presented with altered mental status and persistent hypoglycemia requiring continuous intravenous dextrose, in the context of suspected attempted benzodiazepine abuse. Supratherapeutic glyburide levels of 1198 and 647 ng/mL were measured in these patients. CONCLUSIONS: These are two cases of glyburide poisonings from ingestion of "street Valium" that have been confirmed by laboratory testing. PMID- 21978879 TI - 5-oxoprolinemia causing elevated anion gap metabolic acidosis in the setting of acetaminophen use. AB - BACKGROUND: Anion gap metabolic acidosis is typically encountered in the emergency department (ED) setting as the result of shock, other endogenous metabolic derangements, or from exogenous toxicants. The differential diagnosis for toxicant-related acidosis (exemplified by common mnemonics) emphasizes acute overdose. CASE REPORT: The case we present manifested an anion gap (AG) metabolic acidosis due to a chronic intoxication: acetaminophen (APAP) overuse over a period of weeks. Lactic acidemia did not account for the AG. In this case, chronic APAP overuse, combined with decreased caloric intake and weight loss, was associated with excess 5-oxoproline (pyroglutamic acid), an organic acid accounting for the AG metabolic acidosis. Overproduction of 5-oxoproline is attributed to depleted glutathione stores, leading to perturbation in the gamma glutamyl cycle. The patient was treated with supportive care and with N acetylcysteine (NAC). By repleting glutathione, NAC may facilitate the resolution of excess 5-oxoproline. CONCLUSIONS: The ED differential diagnosis of AG metabolic acidosis in chronic APAP overuse, especially with concomitant nutritional compromise, should include 5-oxoprolinemia. PMID- 21978881 TI - Mentorship relations among academician nurses in Turkey: an assessment from the viewpoints of mentors and mentees. AB - The research was conducted with a descriptive and comparative design to determine how academic nurses (instructors-research assistants) perceive the mentorship relations among themselves. The research was carried out in 10 schools of nursing that offer graduate level education in Turkey, and the data were collected from those academics who are employed in these institutions and who agreed to participate in the research. The data are composed of personal information forms and mentorship scales filled out by 238 academic nurses. The collected data were assessed using SPSS 11.5 software to run percentage and frequency distribution, Cronbach's Alpha analysis, ANOVA, t-test, Kruskal Wallis, Mann Whitney U and--for advanced analysis--Tukey HSD tests. This research determined that mentors and mentees consider the relationship between themselves as mostly a teacher-student relationship, they experience lack of interaction due to shortness of time, mentors tend to evaluate themselves more positively and mentees at the master's level evaluate mentors more positively. In addition, while mentees evaluated assistant professor mentors more positively, assistant professor mentors constituted the group that evaluated itself in the most negative manner. Moreover, mentors with higher academic experiences evaluated themselves more positively. PMID- 21978880 TI - Contribution of epigenetic alteration of BRCA1 and BRCA2 genes in breast carcinomas in Tunisian patients. AB - OBJECTIVE: The aim of this study was to evaluate the contribution of the BRCA1 and BRCA2 promoter methylation in the pathogenesis of sporadic breast cancer in Tunisian patients. METHODS: Breast carcinoma tissues (n=117) and available paired normal breast tissues (n=65) from Tunisian women who had no family history were investigated for the methylation status of BRCA1 and BRCA2 promoters using methylation-specific PCR. Breast specimens from women without carcinoma (16 fibroadenomas and 5 mastopathies) were used as control. RESULTS: Hypermethylation of BRCA1 and BRCA2 promoters was detected respectively in 60.7% and 69.2% of the carcinoma tissues, and in only 7.7% and 4.6% of the paired normal breast tissues. None of the fibroadenomas and mastopathies showed hypermethylation. Correlations were found between BRCA1 and BRCA2 hypermethylation and decrease in their mRNA expression (p=0.02 and p=0.009, respectively). Moreover, BRCA1 methylation correlates with patients age (p=0.01) and triple negative (ER-, PR-, HER2-) tumors (p=0.01). Patients with methylated BRCA1 and/or BRCA2 had a significant prolonged survivals compared to those with unmethylated tumors (p=0.002). CONCLUSION: Our results suggest an important role of BRCA1 and BRCA2 promoter methylation in breast cancer development in the Tunisian population. PMID- 21978882 TI - Hippocampal effects of neuronostatin on memory, anxiety-like behavior and food intake in rats. AB - A 13-amino acid peptide named neuronostatin (NST) encoded in the somatostatin pro hormone has been recently reported. It is produced throughout the body, particularly in brain areas that have significant actions over the metabolic and autonomic regulation. The present study was performed in order to elucidate the functional role of NST on memory, anxiety-like behavior and food intake and the hippocampal participation in these effects. When the peptide was intra hippocampally administered at 3.0 nmol/MUl, it impaired memory retention in both, object recognition and step-down test. Also, this dose blocked the hippocampal long-term potentiation (LTP) generation. When NST was intra-hippocampally administered at 0.3 nmol/MUl and 3.0 nmol/MUl, anxiolytic effects were observed. Also, the administration in the third ventricle at the higher dose (3.0 nmol/MUl) induced similar effects, and both doses reduced food intake. The main result of the present study is the relevance of the hippocampal formation in the behavioral effects induced by NST, and these effects could be associated to a reduced hippocampal synaptic plasticity. PMID- 21978884 TI - Organelles do not colocalize with mRNA granules in post-ischemic neurons. AB - Following global brain ischemia and reperfusion, it is well-established that neurons undergo a translation arrest that is reversible in surviving neurons, but irreversible in vulnerable neurons. We previously showed a correlation between translation arrest in reperfused neurons and the presence of granular mRNA containing structures we termed "mRNA granules." Here we further characterized the mRNA granules in reperfused neurons by performing colocalization studies using fluorescent in situ hybridization for poly(A) mRNAs and immunofluorescence histochemistry for markers of organelles and mRNA-binding proteins. There was no colocalization between the mRNA granules and markers of endoplasmic reticulum, cis- or trans-Golgi apparatus, mitochondria, microtubules, intermediate filaments, 60S ribosomal subunits, or the HuR ligands APRIL and pp32. The mRNA granules colocalized with the neuronal marker NeuN regardless of the relative vulnerability of the neuron type. RNA immunoprecipitation of HuR from the cytoplasmic fraction of 8 h reperfused forebrains selectively isolated hsp70 mRNA suggesting the mRNA granules are soluble structures. Together, these results rule out several organelle systems and a known HuR pathway as being directly involved in mRNA granule function. PMID- 21978883 TI - Role of Abeta-receptor for advanced glycation endproducts interaction in oxidative stress and cytosolic phospholipase A2 activation in astrocytes and cerebral endothelial cells. AB - Blood-brain barrier (BBB) dysfunctions have been implicated in the progression of Alzheimer's disease. Cerebral endothelial cells (CECs) and astrocytes are the main cell components of the BBB. Although amyloid-beta oligomers (Abeta42) have been reported to mediate oxidative damage to the CECs and astrocytes and trigger the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway, the cell surface binding site for Abeta42 and exact sequence of these events have yet to be elucidated. In this study, the receptor for advanced glycation endproducts (RAGE) was postulated to function as a signal transducing cell surface receptor for Abeta42 to induce reactive oxygen species (ROS) generation from NADPH oxidase and trigger downstream pathways for the phosphorylation of extracellular signal-regulated kinases (ERK1/2) and cytosolic phospholipase A2 (cPLA2). We found that Abeta42 competed with the anti-RAGE antibody (Ab(RAGE)) to bind to RAGE on the surfaces of CECs and primary astrocytes. In addition, Ab(RAGE) abrogate Abeta42-induced ROS production and the colocalization between the cytosolic (p47-phox) and membrane (gp91-phox) subunits of NADPH oxidase in both cell types. Ab(RAGE) as well as NADPH oxidase inhibitor and ROS scavenger suppressed Abeta42-induced ERK1/2 and cPLA2 phosphorylation in CECs. At the same time, only Ab(RAGE), but neither NADPH oxidase inhibitor nor ROS scavenger, inhibited the ERK1/2 pathway and cPLA2 phosphorylation in primary astrocytes. Therefore, this study demonstrates that NADPH oxidase complex assembly and ROS production are not required for Abeta42 binding to RAGE at astrocytic surface leading to sequential phosphorylation of ERK1/2 and cPLA2, and suggests the presence of two different RAGE-dependent downstream pathways in the CECs and astrocytes. PMID- 21978885 TI - Effect of loganin on experimental diabetic nephropathy. AB - Connective tissue growth factor (CTGF) plays a pathogenic role in diabetic nephropathy (DN). Loganin, an iridoid glucoside compound was isolated from Cornus officinalis Sieb. et Zucc. This study was conducted to investigate the efficacy of loganin on DN and to elucidate the potential mechanism. High glucose (HG) stimulated cultured human renal proximal tubular epithelial cells (HK-2) analyzed CTGF expression by Western blotting and investigated whether extracellular signal regulated kinase (ERK) signaling pathway was involved. Streptozotocin (STZ) induced experimental DN, randomized to receive intragastric (i.g.) of loganin. Renal tissue, blood and urine samples were collected to determine and analyze. In vitro study, loganin reduced CTGF excretion in HG-induced HK-2 cells through the ERK signaling pathway. In vivo study, I.g. of loganin 5 mg/kg or 10 mg/kg significantly ameliorated renal function and increased body weight. Meanwhile, loganin reduced renal CTGF expression by immunohistochemical staining, reduced serum levels of CTGF. Besides, there were no significant differences in blood sugar levels between the loganin groups compared to the STZ-treated group. Furthermore, loganin ameliorated renal pathology. These results suggested that loganin exerts an early renal protective role to DN. Inhibition of CTGF may be a potential target in DN therapy, which highlights the possibility of using loganin to treat DN. PMID- 21978886 TI - Salidroside inhibits migration and invasion of human fibrosarcoma HT1080 cells. AB - Oxidative stress plays an important role in tumorigenesis and metastasis. Salidroside, a phenylpropanoid glycoside isolated from Rhodiola rosea L., shows potent antioxidant property. Here we investigated the inhibitory effects of salidroside on tumor metastasis in human fibrosarcoma HT1080 cells in vitro. The results indicated that salidroside significantly reduced wound closure areas of HT1080 cells, inhibited HT1080 cells invasion into Matrigel-coated membranes, suppressed matrix metalloproteinases (MMP-2 and MMP-9) activity, and increased tissue inhibitor of metalloproteinase-2 (TIMP-2) expression in a dose-dependent manner in HT1080 cells. Salidroside treatment upregulated the E-cadherin expression, while downregulated the expression of beta1-integrin. As an antioxidant, salidroside inhibited the intracellular reactive oxygen species (ROS) formation in a dose-dependent manner. The results also showed that salidroside could inhibit the activation of protein kinase C (PKC) and the phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) in a dose-dependent manner. In conclusion, these results suggest that salidroside inhibits tumor cells metastasis, which may due to its interfere in the intracellular excess ROS thereby down-regulated the ROS-PKC-ERK1/2 signaling pathway. PMID- 21978887 TI - Serum IgE and eosinophil count in allergic rhinitis--analysis using a modified Bayes' theorem. AB - BACKGROUND: To use probability theory to establish threshold values for total serum IgE and eosinophil counts that support a diagnosis of allergic rhinitis and to compare our results with previously published data. METHODS: Prospective study of rhinitis patients using a modified version of Bayes' theorem. Study included 125 patients at the West Los Angeles VA Medical Center diagnosed with rhinitis who completed allergy consultation and immediate hypersensitivity skin testing. RESULTS: Eighty-nine of 125 patients were atopic by prick and/or intradermal skin testing. Using a modified version of Bayes' theorem and positive and negative probability weights, calculations for different thresholds of serum IgE and eosinophil counts were summated and a posttest probability for atopy was calculated. Calculated posttest probabilities varied according to the threshold used to determine a positive or negative test; however, IgE thresholds greater than 140IU/ml and eosinophil counts greater that 80cells/ml were found to have a high probability of predicting atopy in patients with rhinitis. Moreover, IgE had a greater influence than eosinophil count in determining posttest probability of allergy in this population. Considerable differences were noted in the IgE levels of atopic and non-atopic patients, including those with asthma or a history of smoking. However, these differences were not observed with eosinophil levels. CONCLUSIONS: Using a modified version of Bayes' theorem to determine posttest probability, IgE threshold levels greater than 140IU/ml and eosinophil counts greater than 80cells/ml in an individual with clinical signs and symptoms of rhinitis are likely to correlate with an atopic aetiology. This model of probability may be helpful in evaluating individuals for diagnostic skin testing and certain types of allergy-modifying treatment. PMID- 21978888 TI - Role of laryngoscopy in children with respiratory complaints and suspected reflux. AB - BACKGROUND: In recent years, laryngopharyngeal reflux (LPR) in children has been taken into consideration. OBJECTIVE: The aim of this study was to assess the laryngoscopic findings in children diagnosed LPR and/or gastro-oesophageal reflux (GERD). METHODS: The findings of 49 patients with at least one or more respiratory complaint such as chronic cough, wheezing, hoarseness, recurrent laryngitis, and throat clearing/postnasal discharge suggesting LPR were evaluated retrospectively. The diagnosis of LPR+GERD or GERD was done by the clinical history and 24 h double-probe pH monitoring and/or scintigraphy. RESULTS: Thirty eight out of 49 patients examined by laryngoscopy underwent 24 h double-probe pH monitoring and/or scintigraphy. Thirty of them were diagnosed as LPR+GERD or GERD by any test positivity. Twelve of 30 patients diagnosed with LPR+GERD or GERD had a positive laryngeal finding on the examination of fibre optic laryngoscopy. The most common finding with eight cases was arytenoid erythema A sensitivity of 40% and specificity of 50% for the laryngoscopy in the diagnosis of LPR/GERD were found. CONCLUSION: In children with unexplained respiratory symptoms, laryngopharyngeal reflux should be suspected. Therefore, until enough data on this issue in the literature accumulates, the history and the laboratory findings of the patients obtained from various techniques to document paediatric LPR should be evaluated together. PMID- 21978889 TI - Scorpion and spider venom peptides: gene cloning and peptide expression. AB - This communication reviews most of the important findings related to venom components isolated from scorpions and spiders, mainly by means of gene cloning and expression. Rather than revising results obtained by classical biochemical studies that report structure and function of venom components, here the emphasis is placed on cloning and identification of genes present in the venomous glands of these arachnids. Aspects related to cDNA library construction, specific or random ESTs cloning, transcriptome analysis, high-throughput screening, heterologous expression and folding are briefly discussed, showing some numbers of species and components already identified, but also shortly mentioning limitations and perspectives of research for the future in this field. PMID- 21978890 TI - Engineering of living autologous human umbilical cord cell-based septal occluder membranes using composite PGA-P4HB matrices. AB - Interventional closure of intracardiac wall defects using occluder devices has evolved as a highly attractive treatment option. However, incomplete and delayed healing reactions often result in a major risk of residual defects, thromboembolism, or device fractures. Biodegradable living tissue engineered occluder membranes (TEOMs) could provide autologous thromboresistant implants with growth and remodeling capacities. PGA-P4HB composite matrices were seeded with human umbilical cord-derived cells or vascular-derived control cells and exposed to static (n = 19) or dynamic (n = 13) conditioning. Harvested TEOMs were integrated into occluder frameworks, exposed to crimping and delivered into pre formed defects of juvenile porcine hearts. Dynamically conditioned TEOM constructs showed higher collagen formation in histology than static constructs with significantly higher stiffness moduli in uniaxial tensile testing. Grating interferometry revealed substantial but inhomogeneous cone-like degradation of the composite matrices in dynamic conditioning. The crimping and delivery procedures resulted in no significant changes in macroscopy, histo-morphology, cellular viability, DNA or hydroxyproline content, and scanning electron microscopy findings. Here, we present the in vitro fabrication, crimping and experimental delivery of living human umbilical cord-cell derived TEOMs based on composite matrices as a potential future autologous therapy of intracardiac wall defects. PMID- 21978891 TI - Effects of nanoparticle coatings on the activity of oncolytic adenovirus-magnetic nanoparticle complexes. AB - Limitations to adenovirus infectivity can be overcome by association with magnetic nanoparticles and enforced infection by magnetic field influence. Here we examined three core-shell-type iron oxide magnetic nanoparticles differing in their surface coatings, particle sizes and magnetic properties for their ability to enhance the oncolytic potency of adenovirus Ad520 and to stabilize it against the inhibitory effects of serum or a neutralizing antibody. It was found that the physicochemical properties of magnetic nanoparticles are critical determinants of the properties which govern the oncolytic productivities of their complexes with Ad520. Although high serum concentration during infection or a neutralizing antibody had strong inhibitory influence on the uptake or oncolytic productivity of the naked virus, one particle type was identified which conferred high protection against both inhibitory factors while enhancing the oncolytic productivity of the internalized virus. This particle type equipped with a silica coating and adsorbed polyethylenimine, displaying a high magnetic moment and high saturation magnetization, mediated a 50% reduction of tumor growth rate versus control upon intratumoral injection of its complex with Ad520 and magnetic field influence, whereas Ad520 alone was inefficient. The correlations between physical properties of the magnetic particles or virus complexes and oncolytic potency are described herein. PMID- 21978893 TI - 9-1-1: PCNA's specialized cousin. AB - All living organisms are vulnerable to DNA damage. Cells respond to this hazard by activating a complex network of checkpoint and repair proteins to preserve genomic integrity. The DNA-encircling, ring-shaped heterotrimeric 9-1-1 complex, a relative of the replication protein PCNA, is a central coordinator of these events. 9-1-1 is loaded to damaged sites where it serves as a platform for the selective recruitment of checkpoint and repair proteins. In this Opinion article, 9-1-1 and proliferating cell nuclear antigen (PCNA) are compared and discussed in light of their respective structures and functions. We propose that the interaction partners of 9-1-1 possess specific 9-1-1-interaction boxes, which discriminate between 9-1-1 and PCNA thereby enabling specific interactions with individual 9-1-1 subunits. PMID- 21978894 TI - Diseases of the odontoid and craniovertebral junction with management by endoscopic approaches. AB - Surgical approaches to the craniovertebral junction (CVJ) can result in dysfunction of the upper aerodigestive tract. However, few data are available regarding the incidence of complications after such surgery. Evaluation of a CVJ lesion for treatment must establish the biology, transverse and longitudinal extent of the lesion, and the preoperative and postoperative stability of the spine. Endoscopic approaches to the CVJ, which should reduce the expected morbidity of an open transoral approach, have been described recently. This article reviews common pathologies of the CVJ and surgical approaches, and provides an evidence-based analysis of whether endoscopic approaches reduce velopharyngeal insufficiency. PMID- 21978895 TI - Cholesterol granuloma of the petrous apex. AB - The traditional approaches to symptomatic cholesterol granuloma (CG), the most common benign pathologic lesion of the petrous apex, have historically been transotic, including middle fossa, translabyrinthine, retrocochlear, or infra- or retrolabyrinthine approaches. These approaches were often fraught with risk to the vestibular or cochlear apparatus, the need for brain retraction, or lack of a natural drainage pathway after marsupialization of the granuloma. This article reviews the literature on the transnasal approach to petrous apex CGs, including medial, medial with carotid medialization, and transpterygoid approaches. Of the 19 reported CGs treated with endoscopic drainage, only one recurrence was noted. PMID- 21978892 TI - BAX unleashed: the biochemical transformation of an inactive cytosolic monomer into a toxic mitochondrial pore. AB - BAX, the BCL-2-associated X protein, is a cardinal proapoptotic member of the BCL 2 family, which regulates the critical balance between cellular life and death. Because so many medical conditions can be categorized as diseases of either too many or too few cells, dissecting the biochemistry of BCL-2 family proteins and developing pharmacological strategies to target them have become high priority scientific objectives. Here, we focus on BAX, a latent, cytosolic and monomeric protein that transforms into a lethal mitochondrial oligomer in response to cellular stress. New insights into the structural location of BAX's 'on switch', and the multi-step conformational changes that ensue upon BAX activation, are providing fresh opportunities to modulate BAX for potential benefit in human diseases characterized by pathologic cell survival or unwanted cellular demise. PMID- 21978896 TI - Carotid artery injury after endonasal surgery. AB - Carotid artery injury during endonasal surgery is the most feared and catastrophic complication. Internal carotid artery injury is more frequent during skull base surgery, and risk factors include acromegaly, previous revision surgery, and prior radiotherapy and bromocriptine therapy. Nasal packing is frequently used to gain hemostasis, often resulting in vascular occlusion. Recent research recommends the crushed muscle patch treatment as an effect hemostat that maintains vascular patency. Endovascular techniques are recommended for vascular control and complication management. Coil or balloon embolization is preferred in patients with adequate collateral cerebral blood flow, and stent-graft placement or bypass surgery is indicated in those who do not. PMID- 21978897 TI - Endoscopic skull base surgery for sinonasal malignancy. AB - Management of malignant neoplasms of the sinonasal tract and skull base is hampered by the relative low incidence and pathologic diversity of patient presentations. Many studies have reported successful outcomes in the endoscopic management of malignancy since 1996, and these are summarized in this article. Nonsurgical adjuvant therapies are important for locoregional control because surgery occurs in a restricted anatomic space with close margins to critical structures, and distant disease is an ongoing concern in these disorders. There remains a need for collaborative consistent multicenter reporting, and international registries have been established to assist in such efforts. PMID- 21978898 TI - Endoscopic nasopharyngectomy and its role in managing locally recurrent nasopharyngeal carcinoma. AB - Local recurrence after primary radiation of nasopharyngeal carcinoma (NPC) remains an important cause of morbidity and mortality. Salvage treatment using reirradiation or surgery has been shown to improve survival over nontreatment. Surgery is traditionally performed using an open approach. Advances in endoscopic approaches for resection of paranasal sinus tumors have been extended to NPC. This article reviews the treatment options, in particular the role of endoscopic nasopharyngectomy in the management of recurrent NPC. The endoscopic anatomy, surgical principles, and published results on endoscopic nasopharyngectomy are presented. Short-term outcomes for early-stage recurrences are promising but long term follow-up is needed. PMID- 21978899 TI - Skull base chordomas. AB - Skull base chordomas are rare midline malignancies of clival origin that represent one of the most challenging skull base tumors to treat, given their location, invasiveness, potential extension around vital neurovascular structures, and high recurrence rate. Total tumor resection is the mainstay of treatment. The combination of surgery and postoperative irradiation appears to provide the best outcome. PMID- 21978900 TI - Proton beam therapy in skull base pathology. AB - The optimal treatment of chordomas is maximal safe resection followed by radiation therapy. Data have shown that the use of protons has increased the local control of chordomas. Because of their physical properties, proton therapy has a sharp decline at its distal range, thereby minimizing collateral damage. However, this choice of radiation therapy has been limited based on the availability of resources. Given the high cost of proton facilities and improved techniques for other forms of radiation therapy, this article evaluates whether proton therapy is still superior to other radiation techniques in the treatment of chordomas. PMID- 21978901 TI - Functional outcomes for endoscopic and open skull base surgery: an evidence-based review. AB - The goals of treatment of skull base neoplasms are to maximize oncologic outcomes and optimize functional outcomes. Several studies have investigated the former, but fewer examine the latter. This article reviews the available evidence for several functional outcomes, including endocrine, nasal, neurologic, visual, and quality of life outcomes for both endoscopic and open approaches. The quality of evidence for each outcome is compared for endoscopic and open approaches using the Oxford Centre for Evidence-based Medicine guidelines, and recommendations are made. Future longitudinal comparative outcome studies are needed to better delineate the functional status of patients undergoing skull base surgery. PMID- 21978902 TI - Reconstructive options for endoscopic skull base surgery. AB - This review describes the sequential learning from initial free tissue grafting reconstructive techniques to the current use of vascularized flaps. Outcomes and limitations of current endoscopic reconstructive techniques are discussed, including a systematic review of the outcomes of endoscopic endonasal techniques to reconstruct large skull base defects (ESBR). The various endoscopic techniques for local and regional flaps in skull base reconstruction are described. Additionally, EMBASE (1980-December 7, 2010) and Medline (1950 - November 14, 2010) were searched using a search strategy designed to include any endoscopic endonasal reconstruction of the skull base. The manuscripts selected were subject to full text review to extract data on perioperative outcomes for ESBR. Surgical technique was used for sub-group analysis. PMID- 21978903 TI - Training in neurorhinology: the impact of case volume on the learning curve. AB - This article presents a current view of training in neurorhinology and focuses on the level of evidence for the clinical question of "how many cases are needed to achieve proficiency in endoscopic endonasal skull base surgery?" The authors discuss what defines surgical proficiency, what makes up the learning curve and how it shifts with increasing experience, comparisons of learning curves for different skull base surgeries, and conclude with a discussion and recommendations for achieving high-level proficiency. PMID- 21978904 TI - Skull base: meeting place for multidisciplinary collaboration. PMID- 21978905 TI - Two-stage treatment protocol of keratocystic odontogenic tumour in young patients with Gorlin-Goltz syndrome: marsupialization and later enucleation with peripheral ostectomy. A 5-year-follow-up experience. AB - OBJECTIVE: Keratocystic odontogenic tumour (KCOT) is a benign uni- or multicystic intraosseous odontogenic tumour with potential for local destruction and tendency for multiplicity, especially when associated with Gorlin-Goltz syndrome. We suggest a conservative surgical treatment based on marsupialization and later enucleation with peripheral ostectomy in order to preserve jaw's integrity in young patients. METHODS: Three young patients affected of nevoid basal cell carcinoma syndrome (NBCCS or Gorlin-Goltz syndrome) presented large and multiple KCOTs, which have been treated following a two-stage surgical strategy. Initially marsupialization was performed and after a mean period of 10 months, contextually to evident reduction in radiological size image, enucleation with peripheral ostectomy was carried out. RESULTS: All the patients showed high collaboration in daily self-irrigation of the stomia with chlorhexidine 0.2% during the period of marsupialization. Definitive surgical intervention led to complete healing and no signs of recurrence have been observed during a 5-year-follow-up. CONCLUSIONS: The main advantage of this modality is the preservation of important anatomical structures involved in the lesion and jaw's continuity. Therefore in a selected group of cooperative patients, especially those affected of Gorlin-Goltz syndrome, the surgical protocol exposed allows for a less invasive approach with excellent results avoiding extensive disfiguring procedures. PMID- 21978906 TI - Two cases of spontaneous regression of congenital cholesteatomas. AB - Congenital cholesteatoma arises behind a normal, intact tympanic membrane and is most plausibly explained by the persistence of fetal epidermoid formation. It is generally accepted that cholesteatoma in children has greater aggressive growth activity than that in adults. The congenital type of cholesteatoma starts as a small pearl in the middle ear and eventually grows to involve the ossicles and then the attic and mastoid, causing varying degrees of destruction and functional impairment. However, here we report the cases of two children with congenital cholesteatoma which disappeared spontaneously during the follow-up period. To the best of our knowledge, this is the first report on the spontaneous regression of congenital cholesteatoma. On the basis of the two cases, we could take a "wait and watch" attitude for congenital cholesteatoma in the absence of severe infection, hearing loss, or bone destruction in the middle ear. PMID- 21978908 TI - Reading is believing: the truth effect and source credibility. AB - Five experiments explored how source reliability influences people's tendency to rate statements as more credible when they were encountered earlier (the truth effect). Undergraduates read statements from one reliable source and one unreliable source. Statements read multiple times were perceived as more valid and were more often correctly identified on a general knowledge test than statements read once or not at all. This occurred at varying retention intervals whether the statements originated from a reliable or unreliable source, when people had little memory for the statements themselves or their source, and when the discrediting information about the sources came either before or after reading the facts. While repetition aided recognition and source accuracy, both were unaffected by the reliability of the source. Consistent with the source monitoring framework, familiarity may create an illusion of truth for statements when people lack source-specifying cues, especially cues regarding the reliability of the source. PMID- 21978909 TI - The effects of emotional stimuli on target detection: indirect and direct resource costs. AB - The present study was designed to explore the performance costs of negative emotional stimuli in a vigilance task. Forty participants (20 women) performed a vigilance task in two conditions: one with task-irrelevant negative-arousing pictures and one with task-irrelevant neutral pictures. In addition to performance, we measured subjective state (energetic arousal, tense arousal, task related and task-unrelated thoughts) and frontal cerebral activity with near infrared spectroscopy. Overall performance in the negative picture condition was lower than in the neutral picture condition and the negative picture condition had elevated levels of energetic arousal, tense arousal and task-related thoughts. Moreover, there was a significant relationship between the impact of the negative pictures on tense arousal and task-related thoughts and the impact of the negative pictures on performance (in comparison to the neutral picture stimuli task). These results provide support for indirect cost models of negative emotional stimuli on target detection performance. PMID- 21978910 TI - Synchronous protein cycling in batch cultures of the yeast Saccharomyces cerevisiae at log growth phase. AB - The assumption that cells are temporally organized systems, i.e. showing relevant dynamics of their state variables such as gene expression or protein and metabolite concentration, while tacitly given for granted at the molecular level, is not explicitly taken into account when interpreting biological experimental data. This conundrum stems from the (undemonstrated) assumption that a cell culture, the actual object of biological experimentation, is a population of billions of independent oscillators (cells) randomly experiencing different phases of their cycles and thus not producing relevant coordinated dynamics at the population level. Moreover the fact of considering reproductive cycle as by far the most important cyclic process in a cell resulted in lower attention given to other rhythmic processes. Here we demonstrate that growing yeast cells show a very repeatable and robust cyclic variation of the concentration of proteins with different cellular functions. We also report experimental evidence that the mechanism governing this basic oscillator and the cellular entrainment is resistant to external chemical constraints. Finally, cell growth is accompanied by cyclic dynamics of medium pH. These cycles are observed in batch cultures, different from the usual continuous cultures in which yeast metabolic cycles are known to occur, and suggest the existence of basic, spontaneous, collective and synchronous behaviors of the cell population as a whole. PMID- 21978912 TI - Inertia sensor-based guidance system for upperlimb posture correction. AB - Stroke rehabilitation is labor-intensive and time-consuming. To assist patients and therapists alike, we propose a wearable system that measures orientation and corrects arm posture using vibrotactile actuators. The system evaluates user posture with respect to a reference and gives feedback in the form of vibration patterns. Users correct their arm posture, one DOF at a time, by following a protocol starting from the shoulder up to the forearm. Five users evaluated the proposed system by replicating ten different postures. Experimental results demonstrated system robustness and showed that some postures were easier to mimic depending on their naturalness. PMID- 21978911 TI - Intestinal development and differentiation. AB - In this review, we present an overview of intestinal development and cellular differentiation of the intestinal epithelium. The review is separated into two sections: Section one summarizes organogenesis of the small and large intestines, including endoderm and gut tube formation in early embryogenesis, villus morphogenesis, and crypt formation. Section two reviews cell fate specification and differentiation of each cell type within the intestinal epithelium. Growth factor and transcriptional networks that regulate these developmental processes are summarized. PMID- 21978913 TI - Influence of design parameters on cup-stem orientations for impingement free RoM in hip implants. AB - This study was conducted to study the influence of design parameters namely; the head/neck ratio (R), neck-shaft angle (NSA), oscillation angle (OsA) and stem offset (Stheta) on cup-stem orientations namely; the cup inclination (CI), cup anteversion (CA) and stem antetorsion (SA). R is often linked to influence NSA, OsA and impingement. An effort has been made to analyze range of motion (RoM) with NSA greater than 135 degrees and R lower than 2.3 that may produce impingement. This study attempted to answer the following assumptions whether (a) implants with higher H-N ratio can achieve higher oscillations and higher stem antetorsion, (b) stems with higher neck shaft angle can achieve higher cup anteversion with lower stem offset and stem antetorsion, (c) stem with higher offsets can achieve lower cup anteversion with higher stem antetorsion, and (d) lower cup anteversion can be achieved when stem antetorsion is higher. A theoretical and a simulated method were implemented to anaylze RoM until impingement between cup and neck occurred. Cup abduction and anterior opening were held constant for this study. Multivariate prediction models were developed to predict optimal cup-stem orientations for the chosen design parameters of 12 hip implants. Optimal design parameters to achieve an impingement free RoM were as follows: NSA=139.25 degrees , R=3.08, OsA=119.83 degrees , Stheta=34.45mm, CA(predicted)=16.26 degrees , CI(predicted)=42.77 degrees and SA(predicted)=30.37 degrees , respectively. Multivariate models may be further developed for use in surgery planning to achieve optimal component placement. PMID- 21978914 TI - Hemodynamics in the pulmonary artery of a patient with pneumothorax. AB - Pneumothorax is characterized by lung collapse and an alteration of lung geometry, resulting in alterations of the pulmonary artery blood flow. Though many clinical studies and animal experiments have investigated the effects of pneumothorax on the hemodynamics of pulmonary arteries, its precise effects remain unclear. In this patient-specific study, we investigated the effects of lung deformation and vascular resistance increases due to pneumothorax on the pulmonary blood flow during the acute phase and after recovery. Arterial geometry was extracted up to the fifth generation from computed tomography images, and reconstructed. Computational fluid dynamic analysis was performed, for an unsteady laminar flow with resistance at the outlets, in a reconstructed domain. The results demonstrated a change in flow structure during systole between the acute phase and recovery, and were associated with variations in the flow rate ratio between the right and left lungs. We observed a parabolic-like decrease of the volume flow rate ratio in the affected lung as the resistance increased. Thus, the systemic artery blood oxygenation will rely more on the unaffected lung leading to improved oxygenation of the blood under high resistance in the affected lung. These findings are significant in our understanding of ventilation function under a pneumothorax. PMID- 21978915 TI - An enhanced and validated generic thoraco-lumbar spine model for prediction of muscle forces. AB - A direct measurement of the complete loads in the spine continues to remain elusive. Analytical musculoskeletal models to predict the internal loading conditions generally neglect or strongly simplify passive soft tissue structures. However, during large intervertebral motions, passive structures such as ligaments and the stiffness of the intervertebral discs are thought to play a critical role on the muscle forces required for equilibrium. The objective of the present study was to add the short segmental muscles, lumbar ligaments and disc stiffnesses to an existing base musculoskeletal model of the spine in order to establish what role passive soft tissue structures play in spinal loading, but also validate these results against experimentally determined load data. The long trunk muscles not included in previous models, short segmental muscles, lumbar ligaments and disc stiffnesses were implemented into a commercially available musculoskeletal spine model construct. For several activities of daily living, the loads acting on the vertebral bodies were then calculated relative to the value for standing, and then compared to the corresponding values measured in vivo. Good agreement between calculated and measured results could be achieved in all cases, with a maximum difference of 9%. The highest muscle forces were predicted in the m. longissimus (146N) for flexion, in the m. rectus abdominis (363N) for extension, and in the m. psoas major (144N and 81N) for lateral bending and axial rotation. This study has demonstrated that the inclusion of the complete set of muscle and ligament structures into musculoskeletal models of the spine is essential before accurate spinal forces can be determined. For the first time, trend validation of spinal loading has been achieved, thus allowing confidence in the precise prediction of muscle forces for a range of activities of daily living. PMID- 21978917 TI - The full cost and burden of disorders of the brain in Europe exposed for the first time. PMID- 21978916 TI - Prenatal exposure to MDMA alters noradrenergic neurodevelopment in the rat. AB - 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) binds with high affinity to the norepinephrine transporter (NET), making the noradrenergic system a potential target during fetal exposure. Recent data indicate that adult rats that had been prenatally exposed to MDMA display persistent deficits in working memory and attention; behaviors consistent with abnormal noradrenergic signaling in the forebrain. The present study was designed to investigate whether prenatal exposure to MDMA from embryonic days 14-20 affects the structure and/or function of the noradrenergic system of the rat on postnatal day 21. Offspring that were prenatally exposed to MDMA exhibited an increase in noradrenergic fiber density in the prelimbic region of the prefrontal cortex and the CA1 region of the hippocampus that was not accompanied by an increase in the number of noradrenergic neurons in the locus coeruleus. Direct tissue autoradiography using tritiated nisoxetine demonstrated that while NET binding was not altered in the prelimbic cortex, the dentate gyrus, or the locus coeruleus, it was increased in the CA1, CA2, and CA3 regions of the hippocampus. Basal levels of norepinephrine were increased in the prefrontal cortex and the nucleus accumbens of MDMA-exposed rats, as compared to saline-treated controls. These findings indicate that prenatal exposure to MDMA results in structural changes in the noradrenergic system as well as functional alterations in NE neurotransmission in structures that are critical in attentional processing. PMID- 21978918 TI - The use of THP-1 cells as a model for mimicking the function and regulation of monocytes and macrophages in the vasculature. AB - Since their establishment thirty years ago, THP-1 cells have become one of most widely used cell lines to investigate the function and regulation of monocytes and macrophages in the cardiovascular system. However, because this cell line was derived from the blood of a patient with acute monocytic leukemia, the extent to which THP-1 cells mimic monocytes and macrophages in the vasculature is not entirely known. This article serves as a meaningful attempt to address this question by reviewing the recent publications. The interactions between THP-1 cells and various vascular cells (such as endothelial cells, smooth muscle cells, adipocytes, and T cells) provide insight into the roles of the interconnection of monocytes-macrophages with other vascular cells during vascular inflammation, particularly atherogenesis and obesity. Transcriptome, microRNA profile, and histone modifications of THP-1 cells shed new light on the regulatory mechanism of the monocytes-macrophages in response to various inflammatory mediators, such as oxidized low density lipoprotein, lipopolysaccharide, and glucose. These studies hint that under certain defined conditions, THP-1 cells not only resemble primary monocytes-macrophages isolated from healthy donors or donors with disease, such as diabetes mellitus, but also mimic the in situ alteration of macrophages in the adipose tissue of obese subjects and in atherosclerotic lesions. A potential trajectory is to use this cell line to study the novel molecular mechanisms in monocytes and macrophages in relation to the physiology and pathophysiology of the cardiovascular system, however, the conclusion of studies employing THP-1 cells requires further verification using primary cells and/or in vivo models to be generalized to monocytes and macrophages. PMID- 21978919 TI - Association between home arterial stiffness index and target organ damage in hypertension: comparison with pulse wave velocity and augmentation index. AB - OBJECTIVES: To clarify the implications of the home arterial stiffness index (HASI), we compared HASI with other arterial stiffness measures and investigated the association between HASI and hypertensive target organ damage (TOD). METHODS: We assessed brachial-ankle pulse wave velocity (baPWV) and the carotid augmentation index (cAIx) as measures of arterial stiffness and wave reflection, and the left ventricular mass index (LVMI), carotid intima-media thickness (IMT) using ultrasonography, and the urinary albumin/creatinine ratio (UACR) as measures of TOD in 356 never-treated hypertensive subjects. Home blood pressure (BP) was taken in triplicate in the morning and evening, respectively, for 14 consecutive days with a memory-equipped device. HASI was defined as 1 minus the respective regression slope of diastolic on systolic BP. RESULTS: HASI was significantly correlated with age (r = 0.32, P < 0.001), home pulse pressure (r = 0.36, P < 0.001), morning-evening difference in home systolic BP (r = -0.29, P < 0.001), baPWV (r = 0.18, P < 0.001), cAIx (r = 0.16, P = 0.002), carotid IMT (r = 0.26, P < 0.001), and UACR (r = 0.24, P < 0.001), but not with LVMI (r = 0.05, P = 0.38). After adjustment for age and sex, the significant correlation between HASI and baPWV/cAIx was lost. In multivariate regression analyses, HASI and baPWV were significantly associated with carotid IMT (standardized beta = 0.21, P<0.001; beta = 0.14, P = 0.014) and UACR (beta = 0.13, P = 0.018; beta = 0.21, P < 0.001), independently of age, sex, and home mean arterial pressure. On the other hand, cAIx was independently associated only with LVMI (beta = 0.24, P < 0.001). CONCLUSION: These findings indicate that HASI adds nothing to the existing measures of arterial stiffness, but might be a BP component that can aid in the detection of carotid atherosclerosis and renal damage, similar to PWV. PMID- 21978920 TI - Adipocyte P2X7 receptors expression: a role in modulating inflammatory response in subjects with metabolic syndrome? AB - OBJECTIVE: P2X(7) receptor (P2X(7)R), upon its stimulation with extracellular ATP, modulates several inflammatory responses in different cell types. No information is available on its presence in human adipocytes and its potential involvement in the chronic inflammation associated with metabolic syndrome (MS). Therefore, we evaluated P2X(7)R presence and functional activity in adipocytes from visceral (VAT) and subcutaneous (SAT) adipose tissue of patients with MS and controls (CTL). METHODS: Adipocyte gene expression of TNFalpha, IL-6 and PAI-1 (by realtime-PCR) and their plasma concentrations (ELISA); P2X(7)R expression (realtime-PCR, Western blot and immunofluorescence); P2X(7)R functional activity (intracellular calcium fluxes by fluorimetry); cytokine release from adipocytes (ELISA). The inflammasome components were also determined. RESULTS: In VAT, TNFalpha, IL-6 and PAI-1 were more expressed in MS than in CTL. These differences were confirmed in SAT for IL-6 and PAI-1. Plasma IL-6, PAI-1 and TNFalpha levels were higher in MS. P2X(7)R mRNA and protein, identified in both VAT and SAT, were more abundant in MS than in CTL. Immunofluoresce confirmed the typical "ring like" arrangement of P2X(7)R at the plasma membrane. Benzoyl-benzoyl-ATP raised intracellular calcium both in VAT and SAT, and induced IL-6, TNFalpha and PAI-1 release in both MS and CTL cells. This effect was partially inhibited by KN62, specific human P2X(7)R blocker, or by P2X(7)R gene silencing. The inflammasome was more activated in MS than in CTL adipocytes. CONCLUSION: Human adipocytes express functionally active P2X(7)R, which modulate the release of inflammatory cytokines, at least in part via inflammasome activation. Adipocytes from MS patients show an enhanced P2X(7)R expression, which might contribute to the subclinical inflammatory status characterizing these patients and conferring them an increased CV risk. PMID- 21978921 TI - Dietary polyunsaturated fatty acids may increase plasma LDL-cholesterol and plasma cholesterol concentrations in carriers of an ABCG1 gene single nucleotide polymorphism: study in two Spanish populations. AB - BACKGROUND: ABCG1 mediates cellular cholesterol transport, but there is very little known about the influence of ABCG1 polymorphisms on human plasma lipoprotein cholesterol concentrations or on the interactions of these polymorphisms with diet. OBJECTIVE: Our objective was to investigate whether interactions between PUFA intake and ABCG1 polymorphisms modulate associations with plasma total cholesterol (TC), LDL- and HDL-cholesterol in two Spanish populations. METHODS: We grounded our investigation on two general population based studies: the Hortega study (population A) and the Pizarra study (population B). Participants included 1178 individuals (50.0% women, age range 21-85 years) and 763 individuals (66% women, age range 23-73 years) from populations A and B, respectively, without lipid lowering drugs. Subjects were genotyped for ABCG1 variants. Biochemical measurements were taken by standard procedures. Dietary intakes were estimated with a validated questionnaire. RESULTS: In population A, the A allele homozygotes of SNP rs4148102 had higher TC and LDLc concentrations in subjects on a high PUFA diet than did the carriers of the G allele (242.1 +/- 38.9 vs. 198.0 +/- 36.0mg/dL, p = 0.003, and 149.8 +/- 37.9 vs. 111.4 +/- 32.1mg/dL, p = 0.005, respectively), and significant gene-diet interactions were observed (p=0.020 and p = 0.013, respectively). In population B, similar differences in TC and LDLc concentrations were also found in association with this SNP under a high PUFA diet (253.2+/-24.9 vs. 197.7 +/- 39.9 mg/dL, p = 0.009, and 171.8 +/- 20.5 vs. 120.4 +/- 34.2mg/dL, p = 0.004, respectively), but the gene-diet interactions observed were not significant (p = 0.379 and p = 0.422, respectively). In the pooled populations, differences in the TC and LDLc concentrations increased (246.8 +/- 32.9 vs. 198.0 +/- 37.5, p = 6 * 10(-5), and 159.0+/-32.6 vs. 114.3 +/- 33.1, p = 3 * 10(-5), respectively), and significant gene-diet interactions were maintained (p = 0.006 and p = 0.003, respectively). CONCLUSION: In two Spanish populations, the ABCG1 polymorphism rs4148102 was associated with variations in plasma lipoprotein cholesterol concentrations in subjects with high PUFA intakes. Carriers of the AA genotype consuming high PUFA diet showed higher plasma LDLc concentrations. PMID- 21978922 TI - Smoking and FOS expression from blood leukocyte transcripts in patients with coronary artery disease. AB - OBJECTIVE: Analysis of the leukocyte transriptome, in particular the Finkel Biskis-Jinkins Osteosarcoma (c-Fos) gene, which has a prominent role in inflammation, provides new insights into atherosclerosis mechanisms. Although smoking is a major risk factor, the links between smoking status and coronary artery disease (CAD) remains unclear. We aimed to analyze the relationship between smoking status and c-Fos expression in circulating leukocytes of patients with CAD. METHODS: c-Fos expression was measured by RT-Q-PCR, from blood leukocytes of 239 consecutive patients after acute myocardial infarction (MI). The patients were asked about their smoking status and stratified into 3 groups: current smokers (CS) (N = 85), past smokers (PS) (N = 78) and never smokers (NS) (N = 76). RESULTS: NS had a higher risk profile including hypertension, and CS were younger than PS and NS (-13 years and 17 years respectively). There was only a trend towards lower CRP levels in NS and PS than in CS. The mean c-Fos transcript level was slightly higher in CS than in PS and NS (0.924 vs. 0.908 and 0.861 AU, respectively; p = 0.005). By univariate analysis, neither age, nor sex, nor CRP nor white blood cell count was associated with c-Fos transcript levels. By multivariate analysis, CS (vs. PS + NS) was the strongest predictor of the c Fos transcript level, (B = 0.042 +/- 0.014, p = 0.003), even after adjustment for confounding factors (i.e. hypertension, chronic medication, family history of CAD, and prior MI). CONCLUSION: Our work suggests that c-Fos transcript level in blood leukocyte could be considered a cumulative biomarker of smoking. As the c Fos gene has been put forward as a new factor in the progression and severity of atherosclerosis, it could be considered a novel potential pathway of tobacco toxicity in coronary artery disease. PMID- 21978923 TI - Cross-border reproductive care: a future research agenda. AB - Cross-border reproductive care (CBRC) is a rapidly growing phenomenon of interest to governments and regulators, professionals working within the field of assisted reproductive technologies and men and women seeking to use their services. However, to date, discussions have been dominated by media debates and scholarly commentary, with only partial and fragmentary evidence from empirical research studies. This article identifies the pressing gaps in the literature, elucidates the main theoretical and methodological challenges for investigating CBRC and outlines a future research agenda. Cross-border reproductive care (CBRC) is a rapidly growing phenomenon of interest to governments and regulators, professionals working within the field of assisted reproductive technologies and men and women seeking to use their services. However, to date, discussions have been dominated by media debates and scholarly commentary, with only partial and fragmentary evidence from empirical research studies. This article identifies the pressing gaps in the literature, elucidates the main theoretical and methodological challenges for investigating CBRC and outlines a future research agenda. PMID- 21978926 TI - Glycohydrolases beta-hexosaminidase and beta-galactosidase are associated with lipid microdomains of Jurkat T-lymphocytes. AB - Growing evidence suggests the presence of active lysosomal enzymes in extra lysosomal compartments, such as the plasma membrane. Although in the past little attention was paid to glycohydrolases acting on cellular compartments different from lysosomes, there is now increasing interest on plasma membrane-associated glycohydrolases because they should be involved, together with glycosyltransferases, in glycosphingolipids oligosaccharide modification processes regulating cell-to-cell and/or cell-environment interactions in both physiological and pathological conditions. Starting from the previous evidence of the presence of beta-hexosaminidase and beta-galactosidase at the plasma membrane of cultured fibroblasts, we here investigated the association of these glycohydrolases with lipid microdomains of Jurkat T-lymphocytes. Monosialoganglioside GM3 represents the major glycosphingolipid constituent of T cell plasma membrane and its amount largely increases after T-cell stimulation. beta-hexosaminidase and beta-galactosidase cleave specific beta-linked terminal residues from a wide range of glycoconjugates and in particular are involved in the stepwise degradation of GM1 to GM3 ganglioside. Here we demonstrated that fully processed plasma membrane-associated beta-hexosaminidase and beta galactosidase co-distribute with the lipid microdomain markers and co immunoprecipitate with the signalling protein lck in Jurkat T-cell. Furthermore, Jurkat cell stimulation up-regulates the expression and activity of lysosomal beta-hexosaminidase and beta-galactosidase and increases their targeting to lipid microdomains. The non-random distribution of plasma membrane-associated beta hexosaminidase and beta-galactosidase and their localization within lipid microdomains, suggest a role of these enzymes in the local reorganization of glycosphingolipid-based signalling units. PMID- 21978927 TI - Postnatal overfeeding in rats leads to moderate overweight and to cardiometabolic and oxidative alterations in adulthood. AB - In contrast to the masses of data on obesity, few data are available concerning the cardiometabolic and oxidative consequences of moderate overweight. The model of postnatal overfeeding (OF) induces an increase in body weight at weaning that remains during adult life. Litters of Wistar rats were either maintained at 12 pups (normal-fed group, NF), or reduced to 3 pups at birth in order to induce OF. At 6 months of age, metabolic parameters, circulating oxidative stress and aortic and coronary vasoreactivity were assessed. Cardiac susceptibility to ischemia reperfusion injury was also evaluated ex vivo as were markers of cardiac remodeling. OF led to an increase in body weight at weaning (+50%); the increase in body weight persisted throughout adult life, but was less marked (+10%). Significant increases in plasma levels of fasting glucose, insulin and leptin were found in OF rats. An increase in both plasma hydroperoxides and cardiac superoxide dismutase activity and a decrease in plasma ascorbate were found in OF rats. Vasoreactivity was not modified, but ex vivo, after 30 min of ischemia, isolated hearts from OF rats showed lower recovery of coronary flow along with a greater release of LDH. Studies on heart tissues showed an increase in collagen content and increased expression and activity of MMP-2. Our findings show that moderate overweight in adult rats, induced by postnatal overfeeding, leads to both metabolic and oxidative disturbances as well as a higher susceptibility to cardiac injury after ischemia ex vivo, which may be explained, at least in part, by ventricular remodeling. PMID- 21978928 TI - Behavior change, acceptance, and coping flexibility in highly distressed patients with rheumatic diseases: feasibility of a cognitive-behavioral therapy in multimodal rehabilitation. AB - OBJECTIVE: To describe the development and feasibility of the integration of a cognitive-behavioral therapy (CBT) within a multimodal rehabilitation program for highly distressed patients with rheumatic diseases. METHODS: Development included the detailed specification of the theoretical and empirical-based underpinnings of the CBT and the comprehensive description of its design and content. Feasibility was assessed by percentage of eligible patients, attrition and attendance rates, and patient satisfaction. RESULTS: The developed CBT component seeks to decrease psychological distress and improve activities and participation across multiple life domains by accomplishing behavior change, acceptance, and coping flexibility. Motivational interviewing was applied to endorse patients' own reasons to change. Forty percent (35/87) of the eligible patients were admitted to the program. Attendance rate (>95%) was high. Patient satisfaction ranged from 6.8 to 8.0 (10-point scale). CONCLUSION: Integrating CBT within a multimodal rehabilitation program is feasible. An acceptable proportion of the intended patient sample is eligible and patient's attendance and satisfaction is high. PRACTICE IMPLICATIONS: Patients with impaired physical and psychosocial functioning despite adequate medical treatment pose a great challenge. Their treatment outcome may be improved by screening and selecting highly distressed patients and offering them a CBT embedded in multimodal rehabilitation program. PMID- 21978929 TI - The efficacy of nebulized salbutamol, hypertonic saline and salbutamol/hypertonic saline combination in moderate bronchiolitis. AB - BACKGROUND: The mainstay of treatment in bronchiolitis includes oxygenation, aspiration of secretions from the respiratory tract and maintenance of hydration. The first choice medical agent in clinical practice is nebulized bronchodilators, although their place in treatment is controversial. OBJECTIVES: We investigated the therapeutic benefit of nebulized hypertonic (3%) saline (HS), by comparing four different nebulized regimens in the treatment of bronchiolitis in the emergency department. METHODS: A total of 120 infants were included in this randomized, double-blind, prospective study. Infants were grouped according to the nebulized treatment they received: group 1 - salbutamol + normal saline (NS), group 2 - salbutamol + HS, group 3 - HS, group 4 - NS. Heart beat, Clinical Bronchiolitis Severity Score (CBSS) and oxygen saturation of the patients were determined before and after the nebulizations and at 48-72 h after admission by the designated study physician. RESULTS: Post-treatment mean CBSS were significantly lower than pre-treatment scores in all groups (p = 0.0001) with no significant difference within groups. Improvement percentages for CBSSs were significantly higher in infants without a history of atopy treated with HS and NS (p = 0.023, p = 0.0001, respectively). CONCLUSIONS: The CBSSs of all the infants improved after three doses of nebulized therapy regardless of the treatment regimens. The combination of salbutamol with hypertonic saline did not lead to an additive effect in the improvement of CBSSs compared to the standard salbutamol + NS combination. Atopic children benefited from salbutamol/NS combination whereas non-atopic children improved with HS and NS nebulizations based on improvement percentages of CBSS. PMID- 21978930 TI - Correlates of expected positive and negative support for smoking cessation among a sample of chronically ill veterans. AB - OBJECTIVE: To examine demographic, relationship, and smoking history factors related to expected positive and negative support for quitting smoking among chronically ill veterans. METHODS: Data for this report comes from baseline data from a randomized controlled trial of a support-based smoking cessation intervention for veterans with chronic diseases (cancer, cardiovascular disease, hypertension, diabetes, and chronic obstructive pulmonary disease). We used separate multiple linear regression models to analyze relationships between positive and negative support and variables selected for model entry. RESULTS: Veterans in our sample expected high positive and negative support for quitting. Veterans who were married/living as married, had some college education, were female, or named a female support person expected higher levels of positive support. Veterans who named a female or a nonsmoker as a support person expected higher levels of negative support. Males and non-Caucasians also reported higher levels of expected negative support. CONCLUSIONS: Individual differences that influence perceptions of expected support are likely to influence intervention participation and engagement. Thus, understanding factors associated with expected positive and negative support is necessary to optimize future implementation of support-based cessation interventions through better treatment matching. PMID- 21978931 TI - Pancreatic, endocrine and bariatric surgery: the role of robot-assisted approaches. PMID- 21978932 TI - 3D vector control during alveolar ridge augmentation using distraction osteogenesis and temporary anchorage devices: a new technique. AB - This report describes a combined orthodontic surgical technique involving vertical alveolar distraction using temporary anchorage devices (TADs) in cases of massive alveolar ridge bone and teeth loss. A combined surgical orthodontic protocol included presurgical orthodontic preparation and a preimplantation surgical augmentation stage for insertion of a vertical distractor. During the active vertical alveolar distraction process TADs were inserted. Intraoral orthodontic elastics were attached to the main orthodontic archwire exerting multidirectional forces to control the vertical distraction vector. After 3 months of vector controlling and active bone moulding, the TADs were removed. Anterior alveolar ridge augmentation using distraction osteogenesis was achieved. The application of TADs for better anterior segment curvature enabled dental implant insertion, better positioning and restoration. A combined surgical orthodontic management protocol involving vertical alveolar distraction osteogenesis for augmentation purposes is an efficient treatment method to improve alveolar ridge volume for the preimplantation stage. PMID- 21978933 TI - LPA receptor heterodimerizes with CD97 to amplify LPA-initiated RHO-dependent signaling and invasion in prostate cancer cells. AB - CD97, an adhesion-linked G-protein-coupled receptor (GPCR), is induced in multiple epithelial cancer lineages. We address here the signaling properties and the functional significance of CD97 expression in prostate cancer. Our findings show that CD97 signals through Galpha12/13 to increase RHO-GTP levels. CD97 functioned to mediate invasion in prostate cancer cells, at least in part, by associating with lysophosphatidic acid receptor 1 (LPAR1), leading to enhanced LPA-dependent RHO and extracellular signal-regulated kinase activation. Consistent with its role in invasion, depletion of CD97 in PC3 cells resulted in decreased bone metastasis without affecting subcutaneous tumor growth. Furthermore, CD97 heterodimerized and functionally synergized with LPAR1, a GPCR implicated in cancer progression. We also found that CD97 and LPAR expression were significantly correlated in clinical prostate cancer specimens. Taken together, these findings support the investigation of CD97 as a potential therapeutic cancer target. PMID- 21978934 TI - Host response to short-term, single-agent chemotherapy induces matrix metalloproteinase-9 expression and accelerates metastasis in mice. AB - Mounting evidence suggests that bone marrow-derived cells (BMDC) contribute to tumor growth, angiogenesis, and metastasis. In acute reactions to cancer therapy, several types of BMDCs are rapidly mobilized to home tumors. Although this host reaction to therapy can promote tumor regrowth, its contribution to metastasis has not been explored. To focus only on the effects of chemotherapy on the host, we studied non-tumor-bearing mice. Plasma from animals treated with the chemotherapy paclitaxel induced angiogenesis, migration, and invasion of tumor cells along with host cell colonization. Lesser effects were seen with the chemotherapy gemcitabine. Conditioned medium from BMDCs and plasma from chemotherapy-treated mice each promoted metastatic properties in tumor cells by inducing matrix metalloproteinase-9 (MMP9) and epithelial-to-mesenchymal transition. In mice in which Lewis lung carcinoma cells were injected intravenously, treatment with paclitaxel, but not gemcitabine or vehicle, accelerated metastases in a manner that could be blocked by an MMP9 inhibitor. Moreover, chimeric mice reconstituted with BMDC where MMP9 activity was attenuated did not support accelerated metastasis by carcinoma cells that were pretreated with chemotherapy before their introduction to host animals. Taken together, our findings illustrate how some chemotherapies can exert prometastatic effects that may confound treatment outcomes. PMID- 21978935 TI - Cooperative phosphorylation of FADD by Aur-A and Plk1 in response to taxol triggers both apoptotic and necrotic cell death. AB - Administration of the antimitotic chemotherapeutic taxol is known to cause accumulation of the mitotic kinase Aurora-A (Aur-A). Here, we report that Aur-A phosphorylates S203 of the Fas associated with death domain protein (FADD) in response to taxol treatment. In addition, polo-like kinase 1 (Plk1) failed to phosphorylate the Aur-A-unphosphorylatable FADD substitution mutant S203A, indicating that phosphorylation of S203 by Aur-A serves to prime FADD for Plk1 mediated phosphorylation at S194. The double-phosphorylation-mimicking mutant form of FADD, FADD-S194D/S203D (FADD-DD), recruited caspase-8, activating the caspase-dependent cell death pathway. FADD-DD also dissociated the cell death protein RIP1 from FADD, resulting in activation of RIP1 and triggering of caspase independent cell death. Consistent with its death-promoting potential, FADD-DD showed robust tumor suppressor activity. However, single-phosphorylation mimicking mutant forms of FADD, FADD-S194D/S203A (FADD-DA) and FADD-S194A/S203D (FADD-AD), were incapable of carrying out such functions, indicating that double phosphorylation of FADD is critical for the execution of cell death and tumor suppression. Collectively, our data show the existence of cooperative actions between Aur-A and Plk1 mitotic kinases in response to taxol, providing a molecular explanation for the action mechanism of taxol. PMID- 21978936 TI - Relationships between activities, participation, personal factors, mental health, and life satisfaction in persons with spinal cord injury. AB - OBJECTIVE: To clarify relationships between activities, participation, mental health, and life satisfaction in persons with spinal cord injury (SCI) and specify how personal factors (self-efficacy, neuroticism, appraisals) interact with these components. We hypothesized that (1) activities are related directly to participation, participation is related directly to mental health and life satisfaction, and mental health and life satisfaction are 2 interrelated outcome variables; and (2) appraisals are mediators between participation and mental health and life satisfaction, and self-efficacy and neuroticism are related directly to mental health and life satisfaction and indirectly through appraisals. DESIGN: Follow-up measurement of a multicenter prospective cohort study 5 years after discharge from inpatient rehabilitation. SETTING: Eight Dutch rehabilitation centers with specialized SCI units. PARTICIPANTS: Persons (N=143) aged 18 to 65 years at the onset of SCI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Mental health was measured by using the Mental Health subscale of the 36-Item Short Form Health Survey and life satisfaction with the sum score of "current life satisfaction" and "current life satisfaction compared with life satisfaction before SCI." RESULTS: Structural equation modeling showed that activities and neuroticism were related to participation and explained 49% of the variance in participation. Self-efficacy, neuroticism, and 2 appraisals were related to mental health and explained 35% of the variance in mental health. Participation, 3 appraisals, and mental health were related to life satisfaction and together explained 50% of the total variance in life satisfaction. CONCLUSIONS: Mental health and life satisfaction can be seen as 2 separate but interrelated outcome variables. Self-efficacy and neuroticism are related directly to mental health and indirectly to life satisfaction through the mediating role of appraisals. PMID- 21978937 TI - Magnetic resonance imaging relaxation time measurements of the placenta at 1.5 T. AB - Placental insufficiency is a major cause of fetal growth restriction (FGR) and accumulating evidence indicates several aspects of placental morphology are altered in this condition. MRI provides quantitative indices that may be used in non-invasive assessment of the human placenta, such as relaxation time measurements, T1 and T2. We hypothesised that placental relaxation times relate to alterations in placental tissue morphology and hence may be useful in identifying the changes associated with FGR. We report on the first phase of testing this hypothesis, in a study of women in normal pregnancy. AIMS: To assess relaxation time measurements in the placenta in normal pregnancy and correlate these with gestational age and stereological analyses of placental morphology following delivery. METHODS: 30 women underwent MRI examination (1.5 T) between 20 and 41 weeks gestation. Placental T1 and T2 measurements were acquired from a mid-depth placental region, co-localised to a structural scan. Fixed, wax embedded sections of these placentas collected at delivery were stained with hematoxylin/eosin and subjected to stereological analysis. RESULTS: Placental T1 and T2 show a significant negative correlation with gestation, (Pearson correlation p=0.01, 0.03 respectively). 17 placentas were analysed stereologically. In the group as a whole there was no significant correlation between T1 and T2 and morphological features. However, in a subset of 7 pregnancies scanned within a week of delivery, a significant positive correlation was observed between the fibrin volume density and the ratio of fibrin: villous volume densities and T2 (Spearman correlation p=0.02, 0.03 respectively). DISCUSSION: The correlations between placental T1 and T2 and gestation show that these variables are clearly influenced by changes in placental structure. Fibrin might be a key component but further work is needed to fully elucidate the major structural influences on placental T1 and T2. PMID- 21978938 TI - Development of the i-BODE: validation of the incremental shuttle walking test within the BODE index. AB - BACKGROUND: The BODE index has been shown to predict mortality in COPD. The index includes the 6 min walking test as the measure of exercise capacity. The incremental shuttle walking test (ISWT) is an alternative measure of exercise capacity which can be used to prescribe exercise and has been found to correlate well with peak VO2. The objective of the study was to evaluate the incorporation of the ISWT within the BODE index (named the i-BODE) to predict mortality in COPD. METHODS: Data was analysed from 633 patients with COPD attending pulmonary rehabilitation over an 11 year period, and mortality determined a minimum of one year on from initial assessment. An i-BODE score was calculated using ISWT(m) then Cox regression analysis evaluated the capacity of the index to predict risk of death. RESULTS: BMI, ISWT (m), MRC dyspnoea score, pack years and age were all significantly associated with mortality. Cox regression revealed the i-BODE index was an independent and significant predictor of mortality (hazard ratio 1.27 (CI 1.17-1.35), p < 0.001) and Kaplan Meier survival analysis showed each quartile increase in severity in i-BODE score was significantly associated with increased mortality (p < 0.001 by log rank test). CONCLUSION: We have found the i-BODE index to be an independent predictor of mortality in COPD, even when other strong predictors such as age and pack years are adjusted for. We conclude that the ISWT can be successfully substituted for the 6MWT as an alternative measure of exercise capacity within the BODE index. PMID- 21978939 TI - Stitching the gaps in the Canadian public drug coverage patchwork?: a review of provincial pharmacare policy changes from 2000 to 2010. AB - OBJECTIVES: To describe recent changes and identify emergent trends in public drug benefit policies in Canada from 2000 to 2010. METHODS: For each province, we tracked pharmacare design (namely eligibility, premiums, and patient cost sharing) over time for three beneficiary groups: social assistance recipients, seniors, and the general non-senior population. We assess which plan designs are emerging as a national standard, where the gaps in public coverage remain, and implications for progress towards national pharmacare. RESULTS: Expansion of public drug coverage has been limited. For social assistance recipients, first dollar coverage is the standard. Seniors coverage remains varied, though means testing of eligibility or cost-sharing is common. Seniors benefits were significantly expanded in only one province. As of 2010, six provinces have embraced age irrelevant catastrophic income-based coverage, in some, resulting in the elimination of seniors drug benefits. CONCLUSIONS: Universal income-based catastrophic coverage appears to be emerging as an implicit national standard for provincial pharmacare. However, due to the variation and high level of patient cost-sharing required under these programs, convergence on this model does not equate to substantial progress towards expanding coverage or reducing interprovincial disparities. Leverage of federal spending power to promote standards for public drug coverage is necessary to uniformly protect Canadians against high drug costs. PMID- 21978940 TI - Bone marrow expression of poly(ADP-ribose) polymerase underlies diabetic neuropathy via hematopoietic-neuronal cell fusion. AB - Diabetic neuropathy is the most common diabetic complication. The pathogenetic pathways include oxidative stress, advanced glycation end product (AGE) formation, protein kinase C, and NF-kappaB activation, as well as increased polyol flux. These metabolic perturbations affect neurons, Schwann cells, and vasa nervorum, which are held to be the primary cell types involved. We hypothesize that diabetes induces the appearance of abnormal bone marrow-derived cells (BMDCs) that fuse with neurons in the dorsal root ganglia (DRG) of mice, leading to diabetic neuropathy. Neuronal poly(ADP-ribose) polymerase-1 (PARP-1) activation in diabetes is known to generate free radical and oxidant-induced injury and poly(ADP-ribose) polymer formation, resulting in neuronal death and dysfunction, culminating in neuropathy. We further hypothesize that BM-specific PARP expression plays a determining role in disease pathogenesis. Here we show that bone marrow transplantation (BMT) of PARP-knockout (PARPKO) cells to wild type mice protects against, whereas BMT of wild-type cells to PARPKO mice, which are normally "neuropathy-resistant," confers susceptibility to, diabetic neuropathy. The pathogenetic process involving hyperglycemia, BMDCs, and BMDC neuron fusion can be recapitulated in vitro. Incubation in high, but not low, glucose confers fusogenicity to BMDCs, which are characterized by proinsulin (PI) and TNF-alpha coexpression; coincubation of isolated DRG neurons with PI-BMDCs in high glucose leads to spontaneous fusion between the 2 cell types, while the presence of a PARP inhibitor or use of PARPKO BMDCs in the incubation protects against BMDC-neuron fusion. These complementary in vivo and in vitro experiments indicate that BMDC-PARP expression promotes diabetic neuropathy via BMDC-neuron fusion. PMID- 21978942 TI - Modulatory effects of low-dose MDMA on cocaine-induced locomotor activity and place conditioning in rats. AB - Methylenedioxymethamphetamine (MDMA; "Ecstasy") is commonly abused by humans in environments such as nightclubs and rave parties where other drugs of abuse are readily available. Despite the popularity of polysubstance abuse among recreational MDMA users, relatively few controlled experimental studies have documented the neurobehavioral effects of MDMA in combination with other abused substances. This study employed conditioned place preference procedures (CPP) to assess the locomotor activating and place conditioning effects of acute concurrent administration of MDMA (1.5 or 3.0 mg/kg) and cocaine (10 or 20 mg/kg) in rats. Results indicate that low dose MDMA can enhance the locomotor and conditioned rewarding effects of cocaine. These findings may have important implications for understanding the contribution of serotonergic-dopaminergic interactions in the abuse liability of MDMA when used in combination with cocaine or other psychostimulant drugs. PMID- 21978941 TI - Effects of noradrenergic denervation on L-DOPA-induced dyskinesia and its treatment by alpha- and beta-adrenergic receptor antagonists in hemiparkinsonian rats. AB - While L-3,4-dihydroxyphenylalanine (L-DOPA) remains the standard treatment for Parkinson's disease (PD), long-term efficacy is often compromised by L-DOPA induced dyskinesia (LID). Recent research suggests that targeting the noradrenergic (NE) system may provide relief from both PD and LID, however, most PD patients exhibit NE loss which may modify response to such strategies. Therefore this investigation aimed to characterize the development and expression of LID and the anti-dyskinetic potential of the alpha2- and beta-adrenergic receptor antagonists idazoxan and propranolol, respectively, in rats receiving 6 OHDA lesions with (DA lesion) or without desipramaine protection (DA+NE lesion). Male Sprague-Dawley rats (N=110) received unilateral 6-hydroxydopamine lesions. Fifty-three rats received desipramine to protect NE neurons (DA lesion) and 57 received no desipramine reducing striatal and hippocampal NE content 64% and 86% respectively. In experiment 1, the development and expression of L-DOPA-induced abnormal involuntary movements (AIMs) and rotations were examined. L-DOPA efficacy using the forepaw adjusting steps (FAS) test was also assessed in DA- and DA+NE-lesioned rats. In experiment 2, DA- and DA+NE-lesioned rats received pre-treatments of idazoxan or propranolol followed by L-DOPA after which the effects of these adrenergic compounds were observed. Results demonstrated that moderate NE loss reduced the development and expression of AIMs and rotations but not L-DOPA efficacy while anti-dyskinetic efficacy of alpha2- and beta-adrenergic receptor blockade was maintained. These findings suggest that the NE system modulates LID and support the continued investigation of adrenergic compounds for the improved treatment of PD. PMID- 21978943 TI - Effectiveness of pulse oximetry versus fetal electrocardiography for the intrapartum evaluation of nonreassuring fetal heart rate. AB - OBJECTIVES: To compare the effectiveness of pulse oximetry and fetal electrocardiography in the management of labor with nonreassuring fetal heart rate (NRFHR). STUDY DESIGN: This randomized experimental study consisted of two arms. In group 1 we used pulse oximetry and in group 2 we used STAN(r) technology. The participants in each group were 90 pregnant women with a full term singleton fetus in cephalic presentation and cardiotocographic tracings compatible with NRFHR. We compared the following variables: rate of cesarean delivery, indications for operative delivery due to NRFHR, and repercussions on the newborn's acid-base status. RESULTS: The two groups differed significantly in the mode of delivery, with a cesarean delivery rate of 47.6% in group 1 vs. 30% in group 2 (p=0.032). The groups did not differ in the indications for ending labor due to NRFHR (62% vs. 61%, NS). In terms of neonatal outcomes, the 1-min Apgar score was 6 or lower in 17.8% of the group 1 neonates vs. 4.44% of the group 2 neonates (p<0.001). The groups also differed significantly in umbilical cord vein pH (7.23 vs. 7.27) and pCO2 (57.27 vs. 46.86) at birth. CONCLUSIONS: Fetal electrocardiography with the STAN(r) 21 system was more effective in detecting good fetal status and thus in identifying cases in which labor could proceed safely. Intrapartum surveillance with the STAN(r) 21 system reduced the rate of emergency cesarean delivery. PMID- 21978944 TI - Estradiol plus drospirenone therapy increases mammographic breast density in perimenopausal women. AB - OBJECTIVE: To investigate the effects of 17beta-estradiol 1mg plus drospirenone 2mg (E2/DRSP) treatment on mammographic breast density in perimenopausal women. STUDY DESIGN: In this prospective study, 80 healthy perimenopausal women aged 41 49 years were enrolled and assigned to either E2/DRSP (n=40) or a control group (n=40). Mammograms were performed at baseline and after 12 months of treatment. Mammographic breast density was quantified according to the Wolfe classification. RESULTS: We demonstrated an increase in mammographic breast density in 37% (95% CI (confidence interval): 18.8-55.3%) of women treated with E2/DRSP after 12 months. The percentage of women with increased density was 0% (95% CI: 0.0-0.0%) in the control group. The difference in breast density between the E2/DRSP group and the control group was statistically very significant (p<0.001). CONCLUSIONS: E2/DRSP therapy for 12 months in perimenopausal women significantly increased mammographic breast density in comparison to a control group. Further long-term and large scale prospective studies are needed to evaluate this issue. PMID- 21978945 TI - Drosophila strategies to study psychiatric disorders. AB - For decades, Drosophila melanogaster has been used as a model organism to study human diseases, ranging from heart disease to cancer to neurological disorders [9]. For studying neurodegenerative diseases, Drosophila has been instrumental in understanding disease mechanisms and pathways as well as being an efficient tool in drug discovery studies. For some better-understood disorders, such as Fragile X (a mental retardation syndrome), clinical trials are being run, based in part on translational work in flies and rodents. However, Drosophila is currently less used to study psychiatric disorders such as autism, schizophrenia and attention deficit and hyperactivity disorder (ADHD), despite numerous discoveries of disease susceptibility genes that could be explored by reverse genetics or miss expression studies. This deficit might be explained by (1) a lack of reliable tests to study more complex disease (endo)phenotypes in flies, (2) difficulties in translating disease symptoms into animal models and (3) the polygenetic nature of these diseases. In this review we discuss strategies to use D. melanogaster to study complex psychiatric disorders such as schizophrenia, autism and ADHD. Two common features of these diseases may be defective sleep and attention mechanisms, hence calling for better methods for quantifying and screening arousal thresholds in flies. PMID- 21978946 TI - Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer. AB - A novel naphthylmethylimidazole derivative 1 and its related compounds were identified as 17,20-lyase inhibitors. Based on the structure-activity relationship around the naphthalene scaffold and the results of a docking study of 1a in the homology model of 17,20-lyase, the 6,7-dihydro-5H-pyrrolo[1,2 c]imidazole derivative (+)-3c was synthesized and identified as a potent and highly selective 17,20-lyase inhibitor. Biological evaluation of (+)-3c at a dose of 1mg/kg in a male monkey model revealed marked reductions in both serum testosterone and dehydroepiandrosterone concentrations. Therefore, (+)-3c (termed orteronel [TAK-700]) was selected as a candidate for clinical evaluation and is currently in phase III clinical trials for the treatment of castration-resistant prostate cancer. PMID- 21978948 TI - New dammarane-type glucosides as potential activators of AMP-activated protein kinase (AMPK) from Gynostemma pentaphyllum. AB - AMP-activated protein kinase (AMPK) is a key sensor and regulator of glucose, lipid, and energy metabolism throughout the body. Activation of AMPK improves metabolic abnormalities associated with metabolic diseases including obesity and type-2 diabetes. The oriental traditional medicinal herbal plant, Gynostemma pentaphyllum, has shown a wide range of beneficial effects on glucose and lipid metabolism. In this study, we found that G. pentaphyllum contains two novel dammarane-type saponins designated as damulin A (1), 2alpha,3beta,12beta trihydroxydammar-20(22)-E,24-diene-3-O-[beta-D-glucopyranosyl-(1->2)-beta-D glucopyranoside], and damulin B (2), 2alpha,3beta,12beta-trihydroxydammar-20,24 diene-3-O-[beta-D-glucopyranosyl-(1->2)-beta-D-glucopyranoside], that strongly activate AMPK in cultured L6 myotube cells. Damulins A and B also increased beta oxidation and glucose uptake with increasing GluT4 translocation to the plasma membrane in L6 myotube cells. Taken together our results indicate that activation of AMPK by damulins A and B may contribute to beneficial effect of G. pentaphyllum on glucose and lipid metabolism. PMID- 21978947 TI - 'Click' synthesis of dextran macrostructures for combinatorial-designed self assembled nanoparticles encapsulating diverse anticancer therapeutics. AB - With the non-specific toxicity of anticancer drugs to healthy tissues upon systemic administration, formulations capable of enhanced selectivity in delivery to the tumor mass and cells are highly desirable. Based on the diversity of the drug payloads, we have investigated a combinatorial-designed strategy where the nano-sized formulations are tailored based on the physicochemical properties of the drug and the delivery needs. Individually functionalized C(2) to C(12) lipid , thiol-, and poly(ethylene glycol) (PEG)-modified dextran derivatives were synthesized via 'click' chemistry from O-pentynyl dextran and relevant azides. These functionalized dextrans in combination with anticancer drugs form nanoparticles by self-assembling in aqueous medium having PEG surface functionalization and intermolecular disulfide bonds. Using anticancer drugs with logP values ranging from -0.5 to 3.0, the optimized nanoparticles formulations were evaluated for preliminary cellular delivery and cytotoxic effects in SKOV3 human ovarian adenocarcinoma cells. The results show that with the appropriate selection of lipid-modified dextran, one can effectively tailor the self assembled nano-formulation for intended therapeutic payload. PMID- 21978949 TI - 3,4-Disubstituted oxazolidin-2-ones as constrained ceramide analogs with anticancer activities. AB - Heterocyclic analogs of ceramide as 3-alkanoyl or benzoyl-4-(1-hydroxy-2-enyl) oxazolidin-2-ones were designed by binding of primary alcohol and amide in sphinogosine backbone as a carbamate. They were synthesized by addition of acyl halide to the common ring 4-(1-t-butyldimethylsilyloxyhexadec-2-enyl)-oxazolidin 2-one which was elaborated from chiral aziridine-2-carboxylate including stereoselective reduction and ring opening reactions as key steps. Other analogs with different carbon frame at C4 position which is corresponding to the sphingoid backbone were prepared from 3-cyclopentanecarbonyl-4-(1-t butyldimethylsilyloxybut-2-enyl)-oxazolidin-2-one and straight and cyclic alkenes by cross metathesis. All compounds were tested as antileukemic drugs against human leukemia HL-60 cells. Many of them including propionyl, cyclopentanoyl and p-nitrobenzoyl-4-(1-hydroxyhexadec-2-enyl)-oxazolidin-2-ones showed better antileukemic activities than natural C2-ceramide with good correlation between cell death and DNA fragmentation. There is a drastic change of the activities by the carbon chain lengths at C4 position. Cytotoxicity was induced by caspase activation without significant accumulation of endogenous ceramide concentration or any perturbation of ceramide metabolism. PMID- 21978950 TI - Design, synthesis, and biological evaluation of callophycin A and analogues as potential chemopreventive and anticancer agents. AB - Callophycin A was originally isolated from the red algae Callophycus oppositifolius and shown to mediate anticancer and cytotoxic effects. In our collaborative effort to identify potential chemopreventive and anticancer agents with enhanced potency and selectivity, we employed a tetrahydro-beta-carboline based template inspired by callophycin A for production of a chemical library. Utilizing a parallel synthetic approach, 50 various functionalized tetrahydro beta-carboline derivatives were prepared and assessed for activities related to cancer chemoprevention and cancer treatment: induction of quinone reductase 1 (QR1) and inhibition of aromatase, nitric oxide (NO) production, tumor necrosis factor (TNF)-alpha-induced NFkappaB activity, and MCF7 breast cancer cell proliferation. Biological results showed that the n-pentyl urea S-isomer 6a was the strongest inducer of QR1 with an induction ratio (IR) value of 4.9 at 50 MUM [the concentration to double the activity (CD)=3.8 MUM] and its corresponding R isomer 6f had an IR value of 4.3 (CD=0.2 MUM). The isobutyl carbamate derivative 3d with R stereochemistry demonstrated the most potent inhibitory activity of NFkappaB, with the half maximal inhibitory concentration (IC(50)) value of 4.8 MUM, and also showed over 60% inhibition at 50 MUM of NO production (IC(50)=2.8 MUM). The R-isomer urea derivative 6j, having an appended adamantyl group, exhibited the most potent MCF7 cell proliferation inhibitory activity (IC(50)=14.7 MUM). The S-isomer 12a of callophycin A showed the most potent activity in aromatase inhibition (IC(50)=10.5 MUM). PMID- 21978951 TI - Guinea pigs reared in a monochromatic environment exhibit changes in cone density and opsin expression. AB - This study aimed to determine if a monochromatic environment will affect the development of cones in a guinea pig model. Thirty 3-day-old guinea pigs were randomized into three groups and exposed to green, violet, and white light (control) for 8 weeks. The animals were sacrificed and the density of middle wavelength cones (M cones) and short-wavelength sensitive (S cones) and expression of M-opsin and S-opsin were determined. The density of M cones was increased in the green light group as compared to the control group, and decreased in the violet light group as compared to the control group (both, p < 0.05). There was no significant difference in the density of the S cones among the groups (all, p > 0.05). The density of coexpressing cones in the middle retina was significantly increased in the green light group in comparison to the violet light group (p < 0.01). In addition, there was a significant increase in the level of M-opsin as determined by Western blotting and M-opsin mRNA expression as determined by PCR analysis in the green light group as compared to the control group and a significant decrease in violet light group as compared to the control group (all, p < 0.05). No significant difference in S-opsin level or S-opsin mRNA expression was noted among the groups. We concluded that monochromatic lighting affected the density of cones and expression of opsins in a guinea pig model, and this indicates that the retinal color visual system of the guinea pig possess developmental plasticity. PMID- 21978952 TI - Effect of TGFbeta and PDGF-B blockade on corneal myofibroblast development in mice. AB - The purpose of this study was to investigate the role of transforming growth factor beta (TGFbeta) and/or platelet-derived growth factor-B (PDGF-B) blockade on the differentiation of vimentin and alpha-smooth muscle actin (alphaSMA) expressing myofibroblasts associated with haze in mice. Mouse corneas had haze generating irregular PTK (phototherapeutic keratectomy) and topical treatment with the vectors. Six study groups of PTK treated corneas, with four corneas per group in each experiment, were Group 1) treated with TGFbeta-KDEL vector interfering with TGFbeta signaling through anomalous sorting of cytokine bound to the expressed altered receptor; Group 2) treated with PDGF-B-KDEL vector interfering with PDGF signaling through anomalous sorting of cytokine bound to the expressed altered receptor; Group 3) treated with both TGFbeta-KDEL vector and PDGF-B-KDEL vector to interfere with signaling of both cytokines; Group 4) empty pGFPC1 vector; Group 5) empty pCMV vector; and Group 6) no vector treatment control. At one month after surgery, the corneas were analyzed by immunocytochemistry (IHC) for central stromal cells expressing myofibroblast markers vimentin and alphaSMA. The stroma of corneas treated with the TGFbeta KDEL vector alone (p < 0.05) or both the TGFbeta-KDEL and PDGF-B-KDEL vectors (P < 0.05) had significantly lower density of vimentin-positive cells compared to the corresponding control group. The central stroma of corneas treated with the TGFbeta-KDEL vector (p < 0.05) or the PDGF-B-KDEL vector (p < 0.05) had lower density of alphaSMA-positive cells compared to the corresponding control group. The density of alphaSMA-positive stromal cells was also significantly lower (p < 0.05) when both the TGFbeta-KDEL and PDGF-B-KDEL and vectors were applied together compared to the corresponding control groups. This study provides in situ evidence that TGFbeta and PDGF-B have important roles in modulating myofibroblast generation in the mouse cornea after haze-associated injury. PMID- 21978953 TI - Micro RNAs as a new therapeutic target towards leukaemia signalling. AB - Micro RNAs (miRNAs) have emerged as potentially useful and specific agents to regulate transcriptional control of many cellular genes. There is a real prospect that miRNA and other short-length RNA reagents could be useful in a therapeutic setting. Here we outline the control of miRNAs in acute myeloid leukaemia (AML) subtype of human leukaemia, and ask whether miRNA could be important either in the generation of an AML phenotype, or as a variety of agents to combat the disease in the clinic. The use of miRNAs as potential biomarkers of aberrant signalling pathways involved in AML oncogenesis is also discussed. PMID- 21978954 TI - Characterization of glycosylation sites for a recombinant IgG1 monoclonal antibody and a CTLA4-Ig fusion protein by liquid chromatography-mass spectrometry peptide mapping. AB - Liquid chromatography mass spectrometry (LC-MS) peptide mapping can be a versatile technique for characterizing protein glycosylation sites without the need to remove the attached glycans as in conventional oligosaccharide mapping methods. In this way, both N-linked and O-linked sites of glycosylation can each be directly identified, characterized, and quantified by LC-MS as intact glycopeptides in a single experiment. LC-MS peptide mapping of the individual glycosylation sites avoids many of the limitations of preparing and analyzing an entire pool of released N-linked oligosaccharides from all sites mixed together. In this study, LC interfaced to a linear ion trap mass spectrometer (ESI-LIT-MS) were used to characterize the glycosylation of a recombinant IgG1 monoclonal antibody and a CTLA4-Ig fusion protein with multiple sites of N-and O glycosylation. Samples were reduced, S-carboxyamidomethylated, and cleaved with either trypsin or endoproteinase Asp-N. Enhanced detection for minor IgG1 glycoforms (~0.1 to 1.0 mol% level) was obtained by LC-MS of the longer 32 residue Asp-N glycopeptide (4+ protonated ion) compared to the 9-residue tryptic glycopeptide (2+ ion). LC-MS peptide mapping was run according to a general procedure: (1) Locate N-linked and/or O-linked sites of glycosylation by selected ion-monitoring of carbohydrate oxonium fragment ions generated by ESI in-source collision-induced dissociation (CID), i.e. 204, 366, and 292 Da marker ions for HexNAc, HexNAc-Hex, and NeuAc, respectively; (2) Characterize oligosaccharides at each site via MS and MSMS. Use selected ion currents (SIC) to estimate relative amounts of each glycoform; and (3) Measure the percentage of site-occupancy by searching for any corresponding nonglycosylated peptide. PMID- 21978955 TI - Screening and confirmation analysis of stimulants, narcotics and beta-adrenergic agents in human urine by hydrophilic interaction liquid chromatography coupled to mass spectrometry. AB - The chromatographic behaviour of 44 polar compounds (23 beta-adrenergic agents, 11 stimulants, 4 narcotics and 6 phenolalkylamines) included in the list of prohibited substances and methods of the World Anti-Doping Agency, has been investigated under hydrophilic interaction liquid chromatography conditions by application of different mobile phase compositions (percentage of the organic solvent, type and amount of mobile phase additive and ionic strength) and column temperatures. Detection of analytes was performed by a triple quadrupole mass spectrometer in positive ionization mode and selected reaction monitoring acquisition mode after liquid/liquid extraction. Data collected using as stationary phase type-B silica materials from different producers, showed that the best chromatographic conditions in terms of peak shape, selectivity and chromatographic retention were obtained using an initial percentage of acetonitrile of 90%, a column temperature of 35 degrees C, a mobile phase pH of 4.5 and ammonium acetate (5 mM) and acetic acid (0.1%) as mobile phase additives. The selected chromatographic conditions were used to develop screening and confirmation analytical procedures to detect polar compounds in human urine for antidoping purpose. The developed methods were validated in terms of specificity, matrix effect, linearity, precision, accuracy, sensitivity, robustness and repeatability of retention times and relative ion abundances. Such methods offer attractive alternatives and considerable advantages over traditional approaches especially for the analysis of the phenolalkylamines. PMID- 21978957 TI - Mechanisms and principles of N-linked protein glycosylation. AB - N-linked glycosylation, a protein modification system present in all domains of life, is characterized by a high structural diversity of N-linked glycans found among different species and by a large number of proteins that are glycosylated. Based on structural, functional, and phylogenetic approaches, this review discusses the highly conserved processes that are at the basis of this unique general protein modification system. PMID- 21978956 TI - Interstitial pneumonia after autologous hematopoietic stem cell transplantation in B-cell non-hodgkin lymphoma. AB - INTRODUCTION: During the past decade, interstitial pneumonia (IP) is one of the newly recognized adverse events regarding rituximab therapy. However, disease characteristics of IP after autologous hematopoietic stem cell transplantation (ASCT) have not been well-described since the introduction of rituximab. PATIENTS AND METHODS: We retrospectively analyzed 103 patients with B-cell non-Hodgkin lymphoma undergoing ASCT. A propensity scoring system was applied in our analysis to eliminate potential confounding factors of covariates. RESULTS: The total number of patients who developed IP was nine. Five patients developed IP among 57 patients previously treated with rituximab, and four patients developed IP among 46 who were rituximab-naive. Cumulative incidence of IP was 7.8% at 1 year. Among the patients using rituximab, one patient had IP during the peri-engraftment period (cytomegalovirus infection), three patients had IP between 3 and 12 months (Pneumocystis pneumonia [PCP, n = 1] and unknown cause [n = 2]), and the other one patient had IP 3.3 years after ASCT (unknown cause). Four patients in the rituximab-naive group developed IP between 3 and 12 months (PCP [n = 1] and unknown cause [n = 3]). All nine patients had symptomatic episodes before IP, three of which died of IP or secondary infections. Patients receiving a total body irradiation conditioning regimen had a higher risk of IP (odds ratio = 3.6, P < .001), whereas the incidence was not affected by rituximab usage (P = .85, Log-rank test). CONCLUSION: This study shows that the rituximab usage was not identified as a risk factor of IP and that total body irradiation was the only independent risk factor for IP. Close monitoring is encouraged when symptomatic unexplained episodes are identified during follow-up examinations after ASCT. PMID- 21978958 TI - Purification and characterization of YxeI, a penicillin acylase from Bacillus subtilis. AB - The paper reports the purification and characterization of the first penicillin acylase from Bacillus subtilis. YxeI, the protein annotated as hypothetical, coded by the gene yxeI in the open reading frame between iol and hut operons in B. subtilis was cloned and expressed in Eshcherichia coli, purified and characterized. The purified protein showed measurable penicillin acylase activity with penicillin V. The enzyme was a homotetramer of 148 kDa. The apparent K(m) of the enzyme for penicillin V and the synthetic substrate 2-nitro-5 (phenoxyacetamido)-benzoic acid was 40 mM and 0.63 mM, respectively, and the association constants were 8.93*10(2) M(-1) and 2.51*10(5) M(-1), respectively. It was inhibited by cephalosporins and conjugated bile salts, substrates of the closely related bile acid hydrolases. It had good sequence homology with other penicillin V acylases and conjugated bile acid hydrolases, members of the Ntn hydrolase family. The N-terminal nucleophile was a cysteine which is revealed by a simple removal of N-formyl-methionine. The activity of the protein was affected by high temperature, acidic pH and the presence of the denaturant guanidine hydrochloride. PMID- 21978959 TI - Characterizing electrical signals evoked by acupuncture through complex network mapping: a new perspective on acupuncture. AB - The electrical signals are obtained in spinal dorsal root after different manipulations of acupuncture (MA) being taken at the 'Zusanli' point of the experiment rats. After combining the analysis of the data generated from neuronal network model and that evoked by acupuncture, it is found that features of neuronal chaotic rate time series induced by periodic stimuli can be characterized by complex network approach. The features of signals evoked by MA 'nb' 'nx' (twisting) and MA 'tb' 'tx' (lifting and thrusting) are shown to be different according to the topologies of the mapped networks. This study provides us a new perspective on the analysis of acupuncture and may give potential helps on clinical treatment. PMID- 21978960 TI - Two-year clinical follow-up after pulmonary vein isolation using high-intensity focused ultrasound (HIFU) and an esophageal temperature-guided safety algorithm. AB - BACKGROUND AND OBJECTIVE: High-intensity frequency ultrasound (HIFU) can achieve pulmonary vein isolation (PVI), but severe complications have happened. An esophageal temperature (ET)-guided safety algorithm was implemented. We investigated medium-term outcome. METHODS: After left atrial access, HIFU was applied until complete PVI. The safety algorithm was as follows: <=3 complete ablations per pulmonary vein, early abortion when ET >=40.0 degrees C, use of Power Modulation at ET >39.0 degrees C or when after 20 to 30 seconds no change in PV electrograms: to reduce the ablation temperature in the surrounding tissue, acoustic power is switched on and off with a frequency of 1 Hz; in all first ablations, use of Power Modulation after 50% of programmed time. Touch-up radiofrequency ablation when PVI failed. Follow-up included interviews and Holter electrocardiograms. Recurrence was defined as atrial fibrillation (AF) >30 seconds without a blanking period. RESULTS: A total of 28 symptomatic patients (18 males, age 63 years), with paroxysmal AF (n = 19) and persistent AF (n = 9) were included. After a median follow-up of 738 days, 22 of the 28 patients (79%) were free of AF without antiarrhythmic drugs. After 1 repeat procedure with radiofrequency ablation, 5 patients remained free of AF. The complications were as follows: 1 lethal atrial-to-esophageal fistula at day 31, 1 pericardial effusion at day 48, 1 unexplained death at day 49, and 2 persistent phrenic nerve palsies with full recovery within 12 months. CONCLUSIONS: Two-year follow-up after PVI using HIFU and an ET-guided safety algorithm shows success rates similar to those of radiofrequency-based procedures but with higher complication rates. Importantly, the ET-guided safety algorithm failed to prevent severe complications. HIFU does not meet safety standards required for the treatment of AF, and this led to a halt of its clinical use. PMID- 21978961 TI - Thromboembolic risk of the hot- and cold-catheter ablation for atrial fibrillation. PMID- 21978962 TI - The effects of inflammation on heart rate and rhythm in a canine model of cardiac surgery. AB - BACKGROUND: Heart rate (HR) and rhythm disturbances are common after cardiac surgery. This study tests the hypothesis that the inflammation caused by cardiac surgery is an underlying mechanism for postoperative changes in HR, rhythm, and HR variability (HRV). METHOD AND RESULTS: Normal canines (n = 6 per group) were divided into 4 groups: (1) anesthesia, (2) sternotomy and pericardiotomy, (3) atriotomy, and (4) corticosteroids combined with an atriotomy. Continuous electrocardiographic recordings were done preoperatively and for 3 postoperative days. Electrophysiologic testing was done at the initial and terminal surgeries. C-reactive protein level was assessed at each study day, and tissue myeloperoxidase activity was assessed at the terminal study. Measurements of HRV were determined daily to detect changes in autonomic tone. Postoperatively, the HR increased in the pericardiotomy (P = .0005) and atriotomy (P = .001) groups and HRV decreased in both the groups. No significant change occurred in either the HR or HRV in the anesthesia (P = .52) and steroid (P = .16) groups. HRV (triangular index) on postoperative day 3 was correlated with the tissue myeloperoxidase levels (r = -.83; P = .0004). Autonomic blockade with atropine and esmolol resulted in an HR and HRV that were not significantly different between groups. Atrial premature beats occurred postoperatively in the all the groups except the anesthesia group and were independent of the degree of inflammation. CONCLUSION: Cardiac surgery increases the postoperative HR by reducing HRV, mostly because of a reduction in vagal tone. Furthermore, the magnitude of these changes is dependent on the degree of inflammation and is normalized by corticosteroids. PMID- 21978963 TI - Fibroblast-myocyte connections in the heart. PMID- 21978964 TI - The perinexus: a new feature of Cx43 gap junction organization. PMID- 21978965 TI - Celivarone in patients with an implantable cardioverter-defibrillator: adjunctive therapy for the reduction of ventricular arrhythmia-triggered implantable cardioverter-defibrillator interventions. AB - BACKGROUND: Implantable cardioverter-defibrillators (ICDs) remain the treatment of choice for the prevention of life-threatening arrhythmias. However, many patients with ICDs require additional antiarrhythmic therapy to reduce the morbidity associated with recurrent arrhythmia-triggered ICD interventions. OBJECTIVE: Our study aimed to evaluate the safety and efficacy of celivarone in reducing these interventions. METHODS: A total of 153 eligible ICD recipients were randomized to receive either placebo or celivarone 100 or 300 mg once daily for 6 months. The primary end point was the prevention of arrhythmia-triggered ICD therapies. RESULTS: Fewer ventricular tachycardia and ventricular fibrillation episodes were observed in the 300-mg celivarone group than in the placebo group, with a relative risk reduction of 46%, which was not statistically significant. The analysis of all-cause shocks showed a trend toward a decreased number of events in the celivarone 300-mg group. A post hoc analysis of the primary end point in a subgroup of patients in the celivarone 300-mg group, who had received ICD therapy within 1 month of randomization, showed a significant benefit (P = .032). Celivarone was not associated with an increased risk of torsades de pointes, thyroid dysfunction, or pulmonary events. More heart failure events were reported in the celivarone groups than in the placebo group, but the difference was not statistically significant. CONCLUSION: Celivarone tends to reduce ventricular tachycardia-/ventricular fibrillation-triggered ICD therapies. This effect was not statistically significant. There was a trend toward greater efficacy in the 300-mg group, especially in patients undergoing ICD therapy within 30 days prior to randomization. Overall, celivarone was well tolerated. PMID- 21978967 TI - Candida in oral pre-cancer and oral cancer. AB - Oral pre-malignancies and carcinomas are common epithelial pathologies caused by a variety of etiological factors. In the oral cavity, candidiasis is the most frequent opportunistic fungal infection. Since the initial reports of an association between candidiasis with oral pre-cancer and cancer, various theories have been debated regarding the role of candida in development and transformation of oral pre-malignancies. However, the exact role is still unclear. In the present article, we hypothesize a causal role for candidiasis in oral pre-cancer and cancer albeit an indirect one. We also suggest that candida along with other co-factors may play a role in initiation and promotion of carcinogenesis. PMID- 21978966 TI - Prospective comparison of discrimination algorithms to prevent inappropriate ICD therapy: primary results of the Rhythm ID Going Head to Head Trial. AB - BACKGROUND: Inappropriate therapy for supraventricular arrhythmias remains a significant source of morbidity in implantable cardioverter-defibrillator (ICD) recipients. OBJECTIVE: The Rhythm ID Goes Head to Head Trial (RIGHT) was designed to compare rhythm discrimination and inappropriate therapies among patients with ICDs from 2 manufacturers. METHODS: Patients with standard ICD indications were randomized to receive a Guidant VITALITY 2 with Rhythm ID or selective Medtronic pulse generators using the Enhanced PR Logic or Wavelet discrimination algorithms. A single- or dual-chamber device was implanted based on clinical indications and programmed in 2 detection zones with detection enhancements enabled for rates between 150 and 200 bpm. Algorithm performance was compared between randomization groups, stratified by single or dual chamber, for the primary end point of first inappropriate therapy (shock or antitachycardia pacing) for supraventricular arrhythmias. RESULTS: There were 1962 patients enrolled and followed for 18.3 +/- 9.2 months, with no difference in all-cause mortality between groups. There were 3973 treated episodes where electrograms were available and adjudicated. The primary end point of inappropriate therapy occurred in 246 of 985 VITALITY 2 patients vs 187 of 977 specific Medtronic ICD patients (hazard ratio = 1.34; confidence interval = 1.11-1.62; P = .003). Differences in inappropriate therapy were confined to single-chamber ICDs. Inappropriate shocks were more frequent in VITALITY 2 ICDs (hazard ratio = 1.63; confidence interval = 1.29-2.06; P < .001), with most therapies and performance differences occurring at slower rhythms (rates < 175 bpm). CONCLUSION: Rhythm discrimination performed better in the specific Medtronic than in VITALITY 2 ICDs evaluated, particularly for single-chamber devices. Inappropriate therapies, and differences in performance, may be reduced with the use of rate cutoff above 175 bpm. PMID- 21978968 TI - Neglected aspect of the strategy for human breast diseases: trans-areolar drug delivery. AB - Breast cancer is the most common malignancy in women worldwide. Oncoplastic surgery and partial-breast reconstruction have already developed to improve cosmetic outcomes. However, new strategies for breast diseases are still needed. The principles of evolutionary biology and phylogeny can help solve specific medical problems. But the phylogeny of human breast areola had not been researched ever since proposed. The breast areola has a unique phylogeny, it has all different types of skin glands and includes a few hairs towards the periphery. These skin appendages, including Montgomery's glands - whose miniature mammary acini are in the subcutaneous tissue - make the dermal microvascular "sink" phenomenon imperfect, resulting in that more drug molecules can penetrate into deeper tissue. Meanwhile, the wrinkled skin of the areola increases the total delivery area. Here, we emphasize that the human breast areola has the potential to increase transdermal drug delivery to the breast. We anticipate that our hypothesis may help to provide new, optimized therapeutic and prophylactic strategies for the human breast diseases. PMID- 21978969 TI - Therapeutic possibilities of techniques of extracorporeal blood circulation in oncology. AB - Malignant tumors in an advanced phase of diffusion have a very poor prognosis. However, there are conditions in the body which may impede, even if only partially, further spread of the disease. In addition to currently available treatments, other favorable conditions can help to improve the prognosis, even if only relatively, such as the presence of inhibitors of metalloproteinases, antiangiogenic factors, the absence of particular proteins that favor tumor development, and the possibility of positively activating the immune system. The authors believe that in cases where such conditions are concurrent, the addition of a new favorable condition could be very useful. On the other hand, cases of total spontaneous regression of malignancies, even if in metastatic diffusion, are well known. It was recently emphasized that the spread of metastasis of renal cell carcinoma, arising in patients on hemodialysis for a long time, is considerably reduced at the post-mortem examination compared to patients with renal cell carcinoma and not on hemodialysis. This may suggest a positive effect exerted by the dialytic membrane on metastatic spread. The authors hypothesize that extracorporeal circulation of the blood, used mainly for cardiovascular interventions and hemodialysis, could be used by applying filters suitable for cancer treatments, similar to those used in hemodialysis, even if without accomplishing the hemodialytic function, provided there are no objections to their biocompatibility. In this case, the block of metastatic cells could lead to a relative increase in the cellular elements of the immune system (NK cells and T lymphocytes) compared to cancer cells, or rather to the relative reduction in the number of cancer cells compared to NK cells and T lymphocytes. Such a block would prevent any feedback reactions, so frequent and damaging to the prognosis when using overall medical stimulation for the immune system. PMID- 21978970 TI - Deep brain stimulation of the pedunculopontine tegmental nucleus may influence renal function. AB - Deep brain stimulation of the pedunculopontine tegmental nucleus (PPTg) had usually been reported to improve the symptoms of advanced Parkinson's disease. Previous studies showed that neurons in the PPTg involved in the control of the sympathetic outflow to the kidneys. Our recent studies using transneuronal labeling pseudorabies virus (PRV)-614 supported the sympathetic nature of the caudal PPTg. We propose a hypothesis that deep brain stimulation of the PPTg may influence renal function by serotonergic and catecholaminergic pathways. Because PRV-614/tryptophan hydroxylase and PRV-614/tyrosine hydroxylase double-labeled neurons in the compact parts of PPTg (cpPPTg) were not detected, deep brain stimulation of the cpPPTg might not influence renal function. PMID- 21978971 TI - Stroke on awakening and the tissue window for thrombolysis. PMID- 21978973 TI - A neural cell adhesion molecule-derived peptide, FGL, attenuates glial cell activation in the aged hippocampus. AB - Neuroglial activation is a typical hallmark of ageing within the hippocampus, and correlates with age-related cognitive deficits. We have used quantitative immunohistochemistry and morphometric analyses to investigate whether systemic treatment with the Neural Cell Adhesion Molecule (NCAM)-derived peptide FG Loop (FGL) specifically alters neuroglial activation and population densities within the aged rat hippocampus (22 months of age). A series of 50 MUm paraformaldehyde/acrolein-fixed sections taken throughout the dorsal hippocampus (5 animals per group) were immunostained to detect astrocytes (GFAP and S100beta) and microglial cells (CD11b/OX42 and MHCII/OX6), and analysed using computerised image analysis and optical segmentation (Image-Pro Plus, Media Cybernetics). FGL treatment reduced the density of CD11b+ and MHCII+ microglia in aged animals, concomitant with a reduction in immunoreactivity for these phenotypic markers. FGL treatment also markedly reduced GFAP immunoreactivity within all hippocampal subfields in aged animals, without exerting an appreciable effect on the density of S100beta+ cells. These results demonstrate that FGL can indeed regulate neuroglial activation and reduce microglial cell density in the aged hippocampus, and support its potential use as a therapeutic agent in age-related brain disorders. PMID- 21978972 TI - DWI-FLAIR mismatch for the identification of patients with acute ischaemic stroke within 4.5 h of symptom onset (PRE-FLAIR): a multicentre observational study. AB - BACKGROUND: Many patients with stroke are precluded from thrombolysis treatment because the time from onset of their symptoms is unknown. We aimed to test whether a mismatch in visibility of an acute ischaemic lesion between diffusion weighted MRI (DWI) and fluid-attenuated inversion recovery (FLAIR) MRI (DWI-FLAIR mismatch) can be used to detect patients within the recommended time window for thrombolysis. METHODS: In this multicentre observational study, we analysed clinical and MRI data from patients presenting between Jan 1, 2001, and May 31, 2009, with acute stroke for whom DWI and FLAIR were done within 12 h of observed symptom onset. Two neurologists masked to clinical data judged the visibility of acute ischaemic lesions on DWI and FLAIR imaging, and DWI-FLAIR mismatch was diagnosed by consensus. We calculated predictive values of DWI-FLAIR mismatch for the identification of patients with symptom onset within 4.5 h and within 6 h and did multivariate regression analysis to identify potential confounding covariates. This study is registered with ClinicalTrials.gov, number NCT01021319. FINDINGS: The final analysis included 543 patients. Mean age was 66.0 years (95% CI 64.7-67.3) and median National Institutes of Health Stroke Scale score was 8 (IQR 4-15). Acute ischaemic lesions were identified on DWI in 516 patients (95%) and on FLAIR in 271 patients (50%). Interobserver agreement for acute ischaemic lesion visibility on FLAIR imaging was moderate (kappa=0.569, 95% CI 0.504 0.634). DWI-FLAIR mismatch identified patients within 4.5 h of symptom onset with 62% (95% CI 57-67) sensitivity, 78% (72-84) specificity, 83% (79-88) positive predictive value, and 54% (48-60) negative predictive value. Multivariate regression analysis identified a longer time to MRI (p<0.0001), a lower age (p=0.0009), and a larger DWI lesion volume (p=0.0226) as independent predictors of lesion visibility on FLAIR imaging. INTERPRETATION: Patients with an acute ischaemic lesion detected with DWI but not with FLAIR imaging are likely to be within a time window for which thrombolysis is safe and effective. These findings lend support to the use of DWI-FLAIR mismatch for selection of patients in a future randomised trial of thrombolysis in patients with unknown time of symptom onset. FUNDING: Else Kroner-Fresenius-Stiftung, National Institutes of Health. PMID- 21978975 TI - Responses to GHRH plus arginine test are more concordant with IGF-I circulating levels than responses to arginine and clonidine provocative tests. AB - BACKGROUND/OBJECTIVE: Although pharmacological GH stimulation tests are still considered the gold standard for GH deficiency (GHD) diagnosis, they are burdened by poor specificity. The majority of children diagnosed as having GHD show normal GH responses when re-tested at the end of growth, thus questioning the initial diagnosis. We evaluated the concordance between IGF-I levels and GH responses to provocative tests. METHODS: We analyzed 105 GHRH plus arginine tests, 79 arginine tests, and 124 clonidine tests performed in 192 short children. IGF-I levels <= 2SD score (SDS) were considered suggestive for high likelihood of GHD. The percentage of positive and negative results for each test was determined and compared with IGF-I levels, clinical follow-up and response to therapy. RESULTS: In children with IGF-I>-2SDS the arginine test showed a concordance rate of 6.9%, the clonidine test of 28.6%, and GHRH plus arginine test of 70%. In children with IGF-I<=-2SDS the concordance was 96.1%, 85.7%, and 46.4%, respectively. The overall concordance was 66.7% for GHRH plus arginine, 42.7% for clonidine, and 27.8% for arginine tests. CONCLUSION: Our results suggest that GHRH plus arginine test provides the best concordance with the assessment of IGF-I levels thus suggesting that the combination of the two procedures may significantly reduce the need of a second provocative test. PMID- 21978976 TI - Complex acute medicine: the internist in the lead. PMID- 21978977 TI - Chemokine and chemokine receptor blockade in arthritis, a prototype of immune mediated inflammatory diseases. AB - Chemokines and chemokine receptors have been implicated in inflammatory cell recruitment and angiogenesis underlying the pathogenesis of rheumatoid arthritis (RA) and other inflammatory rheumatic diseases. Numerous CXC, CC, C and CX3C chemokines and their receptors have been detected in the arthritic synovium and numerous strategies, including biologics, peptide and other small molecule inhibitors of chemokines and their receptors have given promising results in preclinical studies performed in animal models of arthritis. However, most recent human RA trials using antibodies and synthetic compounds have failed. Reasons for negative results of these RA trials include overlapping actions of multiple chemokines, dose-dependency, both antagonistic and agonistic effects of chemokines, chemokine degradation by proteases, as well as effects of anti inflammatory, regulatory cells. Recent studies have suggested that CCR1 may still be a good target and previous trials may have failed because of the need of sustained CCR1 occupancy throughout the treatment. Therefore, modulation of receptor occupancy may be a feasible option to increase the efficacy of chemokine receptor targeting. PMID- 21978978 TI - Hepatic and renal manifestations in autosomal dominant polycystic kidney disease: a dichotomy of two ends of a spectrum. AB - Autosomal dominant polycystic kidney disease (ADPKD) is a multisystem disorder. It is the most common genetic cause of end-stage renal disease. One frequent extra-renal manifestation is hepatic cyst formation. The majority of ADPKD patients develop complications as a result of renal cyst formation; however, a small proportion develop extensive hepatic disease with minor renal features. Both phenotypes seem to represent the spectrum of ADPKD. This review discusses the current understanding of the pathogenesis of the disease, its manifestations and the mechanisms of cyst formation. Furthermore, it focuses on monitoring the disease and the treatment options currently available. PMID- 21978979 TI - Saturated fat, carbohydrates and cardiovascular disease. AB - The dietary intake of saturated fatty acids (SAFA) is associated with a modest increase in serum total cholesterol, but not with cardiovascular disease (CVD). Replacing dietary SAFA with carbohydrates (CHO), notably those with a high glycaemic index, is associated with an increase in CVD risk in observational cohorts, while replacing SAFA with polyunsaturated fatty acids (PUFA) is associated with reduced CVD risk. However, replacing a combination of SAFA and trans-fatty acids with n-6 PUFA (notably linoleic acid) in controlled trials showed no indication of benefit and a signal toward increased coronary heart disease risk, suggesting that n-3 PUFA may be responsible for the protective association between total PUFA and CVD. High CHO intakes stimulate hepatic SAFA synthesis and conservation of dietary SAFA . Hepatic de novo lipogenesis from CHO is also stimulated during eucaloric dietary substitution of SAFA by CHO with high glycaemic index in normo-insulinaemic subjects and during hypocaloric high CHO/low-fat diets in subjects with the metabolic syndrome. The accumulation of SAFA stimulates chronic systemic low-grade inflammation through its mimicking of bacterial lipopolysaccharides and/or the induction of other pro-inflammatory stimuli. The resulting systemic low-grade inflammation promotes insulin resistance, reallocation of energy-rich substrates and atherogenic dyslipidaemia that concertedly give rise to increased CVD risk. We conclude that avoidance of SAFA accumulation by reducing the intake of CHO with high glycaemic index is more effective in the prevention of CVD than reducing SAFA intake per se. PMID- 21978980 TI - Vancomycin nephrotoxicity: myths and facts. AB - Vancomycin is a key antibiotic in the management of severe Gram-positive infections. Recent emergence of methicillin-resistant staphylococcal strains with reduced susceptibility to vancomycin has prompted internists to administer high dose treatment to achieve trough levels of 15 to 20 mg/l. Such high doses might be causative in nephrotoxicity. The risk further increases in patients who are critically ill and are on vasopressor support and/or concomitant nephrotoxic agents, with baseline deranged renal function, undergoing prolonged duration of therapy and are obese. However, data are insufficient to recommend the superiority of continuous infusion regimens as compared with intermittent dosing. This review discusses the literature pertaining to vancomycin nephrotoxicity. PMID- 21978981 TI - Identification of patients with upper gastrointestinal bleeding who do not need immediate treatment. PMID- 21978982 TI - A case of hyperammonaemic encephalopathy due to valproic acid. AB - A patient with valproic acid induced hyperammonaemic encephalopathy is presented. During chronic treatment with valproic acid this patient developed a potentially life-threatening encephalopathy without signs of liver failure. After discontinuing the valproic acid the patient recovered completely. In the case of a patient presenting with hyperammonaemic encephalopathy, the possibility of the use of valproic acid should not be overlooked. PMID- 21978983 TI - Analysing completion times in an academic emergency department: coordination of care is the weakest link. AB - Congestion with prolonged stay in the emergency department (ED) is associated with poor health outcomes. Many factors contribute to ED congestion. This study investigates the length of time spent in the ED (time to completion) and the factors contributing to prolonged stay in an academic ED. Data of ED patients were prospectively collected during four weeks in February 2010. Presentation time, referrer, discharge destination, and medical specialities involved were registered in 2510 patients. Additional detailed data about relevant time steps were collected from 66 patients in the triage category Emergency Severity Index (ESI) 3. The Pearson's chi-square test and the Mann-Whitney test were used for statistical analysis. Time to completion was longer than four hours in 13% of patients (average in total population 2:23 hours). In ESI 3 patients, 24% stayed longer than four hours in the ED (p<0.001). Internal medicine had most patients exceeding the four-hour target (37%), followed by neurology (29%). Undergoing a CT scan, treatment by multiple specialities, age above 65 years and hospital admission were associated with exceeding the four-hour target (p<0.001). The elapsed time between receiving test results and admission/discharge also influenced the completion time (p<0.001). A significant percentage of vulnerable and ill patients with triage category ESI 3 exceeded the four-hour completion time in our ED. Absence of coordination of care when multiple specialists were involved and delay in the process of decision-making after completion of all diagnostics on the ED were among other factors responsible for this prolonged stay. Improving the coordination of care will, in our opinion, speed up the decision-making process and lead to shortening of completion times in many patients. PMID- 21978984 TI - Multiple osteolytic bone lesions. PMID- 21978985 TI - A tropical disease characterised by rapidly progressive skin lesions and haemolytic anaemia. PMID- 21978986 TI - Facial numbness as a symptom of a systemic disease. PMID- 21978987 TI - A 44-year-old man with cavitary pneumonia and shock. PMID- 21978988 TI - The formulation of polyhedral boranes for the boron neutron capture therapy of cancer. AB - The early promise of boron neutron capture therapy as a method for the treatment of cancer has been inhibited by the inherent toxicity associated with therapeutically useful doses of 10B-containing pharmacophores, the need for target-tissue specificity and the challenges imposed by biological barriers. Although developments in the synthetic chemistry of polyhedral boranes have addressed issues of toxicity to a considerable extent, the optimisation of the transport and the delivery of boronated agents to the site of action--the subject of this review--is a challenge that is addressed by the development of innovative formulation strategies. PMID- 21978989 TI - Indigenous New Zealand honeys exhibit multiple anti-inflammatory activities. AB - Recent evidence suggests a potential role for honeys in mediating clinical inflammation and tissue damage. Here, we investigated the anti-inflammatory activity of a selection of previously untested indigenous New Zealand (NZ) honeys. We found that several, but not all, New Zealand rewarewa, manuka and kanuka honey samples exhibited potent, dose-dependent reduction of human neutrophil superoxide production in vitro. This inhibitory activity did not correlate with levels of known phenolic-based free radical scavengers. Furthermore, the active honeys did not scavenge superoxide generated in a cell free xanthine/xanthine oxidase assay. In C57BL/6 J mice, topical application of manuka and rewarewa honey samples with the highest in vitro activity suppressed arachidonic acid-induced ear oedema, and rewarewa honey suppressed both oedema and leukocyte (monocyte and neutrophil) infiltration. Together, these findings demonstrate that some indigenous NZ honeys exhibit clinically relevant anti inflammatory activity. Further investigation is warranted to identify the active component(s) and mechanisms responsible for these activities and to determine potential applications for anti-inflammatory honeys in the topical treatment of clinical inflammation. PMID- 21978990 TI - A species tree for the Australo-Papuan Fairy-wrens and allies (Aves: Maluridae). AB - We explored the efficacy of species tree methods at the family level in birds, using the Australo-Papuan Fairy-wrens (Passeriformes: Maluridae) as a model system. Fairy-wrens of the genus Malurus are known for high intensities of sexual selection, resulting in some cases in rapid speciation. This history suggests that incomplete lineage sorting (ILS) of neutrally evolving loci could be substantial, a situation that could compromise traditional methods of combining loci in phylogenetic analysis. Using 18 molecular markers (5 anonymous loci, 7 exons, 5 introns, and 1 mitochondrial DNA locus), we show that gene tree monophyly across species could be rejected for 16 of 18 loci, suggesting substantial ILS at the family level in these birds. Using the software Concaterpillar, we also detect three statistically distinct clusters of gene trees among the 18 loci. Despite substantial variation in gene trees, species trees constructed using four different species tree estimation methods (BEST, BUCKy, and STAR) were generally well supported and similar to each other and to the concatenation tree, with a few mild discordances at nodes that could be explained by rapid and recent speciation events. By contrast, minimizing deep coalescences produced a species tree that was topologically more divergent from those of the other methods as measured by multidimensional scaling of trees. Additionally, gene and species trees were topologically more similar in the BEST analysis, presumably because of the species tree prior employed in BEST which appropriately assumes that gene trees are correlated with each other and with the species tree. Among the 18 loci, we also discovered 102 independent indel markers, which also proved phylogenetically informative, primarily among genera, and displayed a ~4-fold bias towards deletions. As suggested in earlier work, the grasswrens (Amytornis) are sister to the rest of the family and the emu-wrens (Stipiturus) are sister to fairy-wrens (Malurus, Clytomyias). Our study shows that ILS is common at the family level in birds yet, despite this, species tree methods converge on broadly similar results for this family. PMID- 21978992 TI - Sex and the capital city: the political framing of syphilis and prostitution in early republican Ankara. AB - In its initial years, the nascent Turkish republic established the Ministry of Health and Social Assistance in order to promote public health. Beyond simply facilitating its modernizing agenda for the emergent nation-state as it sought to define itself against an Ottoman past, this institution was also geared toward remedying a self-defined population crisis by prioritizing and confronting particular diseases and health conditions. One of the maladies of utmost concern was syphilis. Based upon an analysis of official primary sources, this article engages with how the developing republic distinguished and consequently politically constructed-or framed-the syphilis problem from the vantage of its new forward capital, Ankara. Integral to this project of confronting this sexually transmitted disease, public health officials projected upon both this ailment and their understanding of the suitable means for its treatment their own views of what constituted appropriate sexual practices and relations. In doing so, certain subgroups of the population, especially prostitutes, were particularized as targets for surveillance and policing through regimes of licensing and compulsory medical examinations. Stemming from the state's framing of the disease-and its definition of appropriate sexual practices-this article also examines the subsequent legislative and public health education projects that followed. PMID- 21978991 TI - A kinase-anchoring proteins and adenylyl cyclase in cardiovascular physiology and pathology. AB - 3'-5'-Cyclic adenosine monophosphate (cAMP), generated by adenylyl cyclase (AC), serves as a second messenger in signaling pathways regulating many aspects of cardiac physiology, including contraction rate and action potential duration, and in the pathophysiology of hypertrophy and heart failure. A kinase-anchoring proteins localize the effect of cAMP in space and time by organizing receptors, AC, protein kinase A, and other components of the cAMP cascade into multiprotein complexes. In this review, we discuss how the interaction of A kinase-anchoring proteins with distinct AC isoforms affects cardiovascular physiology. PMID- 21978993 TI - Evaluation of a new model of short-term palliative care for people severely affected with multiple sclerosis: a randomised fast-track trial to test timing of referral and how long the effect is maintained. AB - AIMS: In this randomised fast-track phase II trial, the authors examined (1) whether the timing of referral to short-term palliative care (PC) affected selected outcomes, and (2) the potential staff-modifying effect of the short-term PC intervention (whether the effects were sustained over time after PC was withdrawn). METHODS: PC comprised a multiprofessional PC team that provided, on average, three visits, with all care completed by 6 weeks. Recruitment commenced in August 2004 and continued for 1 year. Follow-up was performed for 6 months in both groups. Outcomes were a composite measure of five key symptoms (pain, nausea, vomiting, mouth problems and sleeping difficulty) using the Palliative care Outcome Scale-MS Symptom Scale, and care giver burden was measured using the Zarit (Care Giver) Burden Interview (ZBI). RESULTS: 52 patients severely affected by multiple sclerosis were randomised to receive PC either immediately (fast track group) or after 12 weeks (control group). Patients had a high level of disability (mean Expanded Disability Status Scale: 7.7; median: 8; SD: 1). Following PC, there was an improvement in Palliative care Outcome Scale-MS Symptom Scale score and ZBI score. A higher rate of improvement in ZBI score was seen in the fast-track group. After withdrawal of PC, effects were maintained at 12 weeks, but not at 24 weeks. CONCLUSIONS: Receiving PC earlier has a similar effect on reducing symptoms but greater effects on reducing care giver burden, compared to later referral. In this phase II trial, the authors lacked the power to detect small differences. The effect of PC is maintained for 6 weeks after withdrawal but then appears to wane. PMID- 21978995 TI - Trial registration and declaration of registration by authors of randomized controlled trials. AB - BACKGROUND: Trial registration was introduced to reduce research bias by promoting trial transparency and accountability. We aimed to evaluate the frequency of, and factors associated with, trial registration and declaration of trial registration. METHODS: We selected all randomized controlled trials in kidney transplantation published between October 2005 and December 2010 and determined whether a trial was registered and whether a trial declared their registration in subsequent trial reports. RESULTS: Of 307 eligible trials identified, 24% (74/307) were registered, and of those, 59% (44/74) contained trial registration details within at least one trial report. Trial registration was more likely for trials published more than once, in later years or reported in journals that followed the International Committee of Medical Journal Editors guidelines. Trial registration was less likely for trials that did not declare their funding sources. Registered trials were more likely to declare registration details in related reports if published in later years or in a journal that followed International Committee of Medical Journal Editors guidelines. Trials that did not declare their funding sources were less likely to declare registration details. CONCLUSIONS: Although still suboptimal, the situation is improving over time, with both trial registration and declaration of registration details more likely in later years. PMID- 21978994 TI - Submicromolar Abeta42 reduces hippocampal glutamate receptors and presynaptic markers in an aggregation-dependent manner. AB - Synaptic pathology in Alzheimer's disease brains is thought to involve soluble Abeta42 peptide. Here, sterile incubation in PBS caused small Abeta42 oligomer formation as well as heterogeneous, 6E10-immunopositive aggregates of 80-100kDa. The high molecular weight aggregates (H-agg) formed in a time-dependent manner over an extended 30-day period. Interestingly, an inverse relationship between dimeric and H-agg formation was more evident when incubations were performed at 37 degrees C as compared to 23 degrees C, thus providing an experimental strategy with which to address synaptic compromise produced by the different Abeta aggregates. H-agg species formed faster and to higher levels at 37 degrees C compared to 23 degrees C, and the two aggregate preparations were evaluated in hippocampal slice cultures, a sensitive system for monitoring synaptic integrity. Applied daily at 80-600nM for 7days, the Abeta42 preparations caused dose dependent and aggregation-dependent declines in alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionate (AMPA) and N-methyl-d-aspartate (NMDA) receptor subunits as well as in presynaptic components. Unlike the synaptic effects, Abeta42 induced only trace cellular degeneration that was CA1 specific. The 37 degrees C preparation was less effective at decreasing synaptic markers, corresponding with its reduced levels of Abeta42 monomers and dimers. Abeta42 dimers decayed significantly faster at 37 degrees C than 23 degrees C, and more rapidly than monomers at either temperature. These findings indicate that Abeta42 can self aggregate into potent synaptotoxic oligomers as well as into larger aggregates that may serve to neutralize the toxic formations. These results will add to the growing debate concerning whether high molecular weight Abeta complexes that form amyloid plaques are protective through the sequestration of oligomeric species. PMID- 21978996 TI - Assessment of the electrophysiological properties of the muscle fibers of a transplanted hand. AB - BACKGROUND: The muscle fibers in a transplanted hand remain denervated for a long period of time after the transplant. This prolonged inactivity may change the electrophysiological membrane properties of muscle fibers, as observed in long term denervation. We investigated whether electrophysiological properties of the muscle fibers are preserved in a transplanted hand even after several months of denervation. Specifically, we assessed the dependence of muscle fiber conduction velocity (CV) on discharge rate in motor units of the abductor digiti minimi muscle. METHODS: Surface electromyography signals were recorded from the transplanted hand of a patient who was 35 years of age at the time of the transplant. In each of 11 experimental sessions performed over a period of 23 months after the transplant, the subject was asked to linearly increase the activation or to maintain a maximum activation of the abductor digiti minimi muscle for 60 sec. Individual motor unit action potentials were identified from the electromyography recordings and muscle fiber CV was estimated for each action potential as a function of the time interval separating the action potential from the preceding discharge (interspike interval [ISI]). RESULTS: The baseline (ISI >1000 msec) CV was 3.8+/-0.3 m/sec. CV decreased monotonically with increasing ISI (R=0.95). For ISI in the range 0 to 10 msec, muscle fiber CV was 24.9%+/ 16.3% higher than the baseline value (P<0.05). CONCLUSIONS: The results indicate that in the investigated muscle, the baseline value of CV and its dependency on discharge rate were similar as in able-bodied individuals, despite a period of several months of denervation. PMID- 21978997 TI - B- and T-lymphocyte attenuator targeting protects against the acute phase of graft versus host reaction by inhibiting donor anti-host cytotoxicity. AB - BACKGROUND: B- and T-lymphocyte attenuator (BTLA) functions as a coinhibitory/costimulatory molecule that belongs to the immunoglobulin superfamily and exhibits a pattern of expression restricted to the hematopoietic compartment. Engagement of BTLA by its ligand, herpes virus entry mediator (HVEM), delivers negative signals to T cells, whereas engagement of HVEM receptor on T cells by surface BTLA expressed on other immune cells costimulates T activation. Previous work has reported that parental donor BTLA knock-out or HVEM knock-out T cells adoptively transferred into nonirradiated F1 recipient mice survived poorly, and the rejection of host hematopoietic cells was attenuated compared with F1 recipients receiving wild-type T cells. METHODS: Parent into nonirradiated immunocompetent F1 murine model of acute graft versus host reaction, which is induced with the adoptive transfer of splenocytes from donor B6 mice (H-2(b)) into F1 recipients (BALB/c*B6, H-2(d/b)), was used as an experimental approach to test the therapeutic effect of targeting BTLA during the course of an allogeneic immune response. RESULTS: We herein provide evidence that administration of an anti-BTLA monoclonal antibody leads to significant reduction of donor anti-host allogeneic immune response against bone marrow and thymus during the acute phase of graft versus host reaction in a parent into nonirradiated F1 murine model of alloreactivity. Anti-BTLA protection against donor anti-host hematopoietic cell rejection correlated with impaired anti-host cytotoxic T-lymphocyte activity than reduction in T-cell number infiltrating host tissues. CONCLUSIONS: These findings place BTLA receptor as a potential immunoregulatory target for the modulation of cytotoxic T-lymphocyte-mediated alloresponses. PMID- 21978999 TI - Efficacy of intravenous Ig therapy in juvenile dermatomyositis. AB - Intravenous immunoglobulin (IVIg) is an adjunctive therapy for juvenile dermatomyositis (JDM) patients with poor response to first-line therapy (corticosteroid resistant; SR) or who are corticosteroid dependent (SD). Patients requiring IVIg are generally expected to have poorer outcomes, leading to confounding by indication in observational studies. Few studies have evaluated IVIg efficacy in JDM. OBJECTIVES: Compared with similar matched controls, to determine if JDM IVIg recipients achieve quiescence sooner and have less disease activity. For SD patients, to determine if IVIg recipients exhibit less disease activity than IVIg-naive patients. METHODS: A retrospective inception cohort of 78 JDM patients was studied. Kaplan-Meier survival determined time to quiescence. Marginal structural modelling was used to account for confounding by indication by incorporating inverse probability of treatment weights to handle patients' unequal likelihood of receiving IVIg. RESULTS: While similar demographically, the 30 IVIg patients demonstrated weaker muscle strength and more had photosensitivity at baseline than the 48 controls. As expected, IVIg patients achieved quiescence later than controls in unadjusted analysis. However, although IVIg patients started with greater disease activity, after accounting for confounding as best possible, they maintained similar or lower disease activity than controls from 30 days to 4 years post-diagnosis. This improvement was most marked in SR patients. Among SD patients, IVIg recipients maintained lower disease activity than IVIg-naive patients. CONCLUSION: This study, involving the largest JDM cohort receiving IVIg to date, applied bias-reduction methods and demonstrated IVIg efficacy in controlling JDM disease activity, particularly for SR patients. PMID- 21978998 TI - Genetic and physical interaction of the B-cell systemic lupus erythematosus associated genes BANK1 and BLK. AB - OBJECTIVES: Altered signalling in B cells is a predominant feature of systemic lupus erythematosus (SLE). The genes BANK1 and BLK were recently described as associated with SLE. BANK1 codes for a B-cell-specific cytoplasmic protein involved in B-cell receptor signalling and BLK codes for an Src tyrosine kinase with important roles in B-cell development. To characterise the role of BANK1 and BLK in SLE, a genetic interaction analysis was performed hypothesising that genetic interactions could reveal functional pathways relevant to disease pathogenesis. METHODS: The GPAT16 method was used to analyse the gene-gene interactions of BANK1 and BLK. Confocal microscopy was used to investigate co localisation, and immunoprecipitation was used to verify the physical interaction of BANK1 and BLK. RESULTS: Epistatic interactions between BANK1 and BLK polymorphisms associated with SLE were observed in a discovery set of 279 patients and 515 controls from northern Europe. A meta-analysis with 4399 European individuals confirmed the genetic interactions between BANK1 and BLK. As BANK1 was identified as a binding partner of the Src tyrosine kinase LYN, the possibility that BANK1 and BLK could also show a protein-protein interaction was tested. The co-immunoprecipitation and co-localisation of BLK and BANK1 were demonstrated. In a Daudi cell line and primary naive B cells endogenous binding was enhanced upon B-cell receptor stimulation using anti-IgM antibodies. CONCLUSION: This study shows a genetic interaction between BANK1 and BLK, and demonstrates that these molecules interact physically. The results have important consequences for the understanding of SLE and other autoimmune diseases and identify a potential new signalling pathway. PMID- 21979000 TI - Use of statins is associated with an increased risk of rheumatoid arthritis. AB - OBJECTIVES: Statins offer significant cardiovascular benefits. Their use, however, influences immune regulation, which may potentially facilitate autoimmunity, eventually resulting in autoimmune diseases such as rheumatoid arthritis (RA).The authors studied whether statin use was associated with an increased risk of developing RA by conducting a case-control study using the Netherlands Information Network of General Practice database. METHODS: The authors identified 508 patients aged 40 years or older with a first-time diagnosis of RA in the period 2001-2006. Each RA case was matched to five controls for age, sex and index date, which was selected 1 year before the first diagnosis of RA. Odds ratios for the first-time diagnosis of RA were verified by a referral to a rheumatologist and/or at least one prescription of disease modifying anti-rheumatic drugs and/or two prescriptions of corticosteroids after the date of first diagnosis. RESULTS: Cases were more often users of statins (15.9%) compared to controls (8.6%). After adjustment for cardiovascular risk factors and use of comedication, statin use was associated with an increased risk of incident RA (adjusted OR, 1.71 (95% CI 1.16 to 2.53); p=0.007). A consistent trend of increasing risk with increased cumulative duration, cumulative defined daily doses and number of prescriptions was not observed. However, a small trend between the potency of statin treatment and the risk of RA was found. CONCLUSIONS: Statin use seems to be associated with an increased risk of developing RA. Our findings should be replicated by additional studies. PMID- 21979001 TI - MRI inflammation at the vertebral unit only marginally predicts new syndesmophyte formation: a multilevel analysis in patients with ankylosing spondylitis. AB - OBJECTIVE: To investigate the relationship between MRI inflammation at the vertebral unit and the formation and growth of syndesmophytes at the same vertebral unit. METHODS: An 80% random sample of the ASSERT database was analysed. MRI were scored using the ankylosing spondylitis (AS) spinal MRI activity score (at baseline, 24 and 102 weeks) and spinal x-rays were scored using the modified Stoke AS spine score (at baseline and 102 weeks). Data were analysed at the patient level and the vertebral unit level using a multilevel approach to adjust for within-patient correlation. RESULTS: There was a slightly increased probability of developing syndesmophytes in vertebral units with MRI activity, which was maintained after adjustment for within-patient correlation (per vertebral unit level) and treatment, and after further adjustment for potential confounders, resulting in significant OR ranging from 1.51 to 2.26. Growth of existing syndesmophytes at the vertebral unit level was not associated with MRI activity. At the patient level only a trend for an association was observed. CONCLUSION: MRI inflammation in a vertebral unit slightly increases the propensity to form a new syndesmophyte in the same vertebral unit, but does not predict the growth of already existing syndesmophytes. Despite this association, the large majority of new syndesmophytes developed in vertebral units without inflammation. The subtle association at the vertebral unit level did not translate into an association at the patient level. PMID- 21979002 TI - Potential involvement of IL-22 and IL-22-producing cells in the inflamed salivary glands of patients with Sjogren's syndrome. AB - OBJECTIVES: In chronic inflammatory disorders, interleukin (IL)-22 may act either as a protective or as a pro-inflammatory cytokine. At mucosal sites, IL-22 is mainly produced by CD4(+) T cells and by a subset of mucosal natural killer (NK) cells expressing the receptor NKp44 (NKp44(+) NK cells). The aim of this study was to investigate the IL-22 expression in the salivary glands of patients with primary Sjogren's syndrome (pSS). METHODS: Minor salivary gland biopsies were obtained from 19 patients with pSS and 16 with non-specific chronic sialoadenitis. Quantitative gene expression analysis by TaqMan real-time PCR and immunohistochemistry for IL-17, IL-22, IL-23 and STAT3 (signal transducer and activator of transcription) was performed on salivary glands from patients and controls. The cellular sources of IL-22 among infiltrating inflammatory cells were also determined by fluorescence-activated cell sorting analysis and immunohistochemistry. RESULTS: IL-22, IL-23 and IL-17 were significantly increased at both protein and mRNA levels in the inflamed salivary glands of patients with pSS. STAT3 mRNA and the tyrosine phosphorylated corresponding protein were also significantly increased in pSS. Th17 and NKp44(+) NK cells were the major cellular sources of IL-22 in patients with pSS. CONCLUSIONS: Our results suggest that, together with IL-17 and IL-23, IL-22 may play a pro inflammatory role in the pathogenesis of pSS. PMID- 21979004 TI - High-interest clones. PMID- 21979003 TI - Life course body mass index and risk of knee osteoarthritis at the age of 53 years: evidence from the 1946 British birth cohort study. AB - INTRODUCTION: The authors examined how body mass index (BMI) across life is linked to the risk of midlife knee osteoarthritis (OA), testing whether prolonged exposure to high BMI or high BMI at a particular period has the greatest influence on the risk of knee OA. METHODS: A population-based British birth cohort of 3035 men and women underwent clinical examination for knee OA at age 53 years.Heights and weights were measured 10 times from 2 to 53 years. Analyses were stratified by gender and adjusted for occupation and activity levels. RESULTS: The prevalence of knee OA was higher in women than in men (12.9% (n=194) vs 7.4% (n=108)). In men, the association between BMI and later knee OA was evident at 20 years (p=0.038) and remained until 53 years (OR per z-score 1.38 (95% CI 1.11 to 1.71)). In women, there was evidence for an association at 15 years (p=0.003); at 53 years, the OR was 1.89 (95% CI 1.59 to 2.24) per z-score increase in BMI. Changes in BMI from childhood in women and from adolescence in men were also positively associated with knee OA. A structured modelling approach to disentange the way in which BMI is linked to knee OA suggested that prolonged exposure to high BMI throughout adulthood carried the highest risk and that there was no additional risk conferred from adolescence once adult BMI had been accounted for. CONCLUSION: This study suggests that the risk of knee OA accumulates from exposure to a high BMI through adulthood. PMID- 21979005 TI - The games begin. PMID- 21979007 TI - The voice of science: let's agree to disagree. PMID- 21979019 TI - Stellar performance nets physics prize. PMID- 21979018 TI - Nobel announcement marred by winner's death. PMID- 21979020 TI - Trillion-dollar brain drain. PMID- 21979021 TI - Europe cuts funding red tape. PMID- 21979022 TI - Secrets of the human genome disclosed. PMID- 21979023 TI - Nature readers flirt with personal genomics. PMID- 21979024 TI - Experts question rankings of journals. PMID- 21979025 TI - Human genetics: Genomes on prescription. PMID- 21979026 TI - Science publishing: The trouble with retractions. PMID- 21979027 TI - Phosphorus cycle: A broken biogeochemical cycle. PMID- 21979032 TI - Athena SWAN awards: Bridging the gender gap in UK science. PMID- 21979033 TI - Pharmaceuticals: Reduce drug waste in the environment. PMID- 21979034 TI - Stem cells: Cloning advance calls for careful regulation. PMID- 21979035 TI - Academic ladder: Discovery inspires those seeking tenure. PMID- 21979036 TI - Research community: Pilot scheme for misconduct database. PMID- 21979037 TI - Degree courses: Energy should form its own discipline. PMID- 21979038 TI - Energy production: Giant dam threatens Brazilian rainforest. PMID- 21979039 TI - Stem cells: Triple genomes go far. PMID- 21979040 TI - Molecular medicine: Defence against oxidative damage. PMID- 21979041 TI - Palaeoanthropology: Malapa and the genus Homo. PMID- 21979042 TI - Statistical physics: Self-aware particles. PMID- 21979043 TI - Muscular dystrophy: A hidden ancestral legacy trumped. PMID- 21979044 TI - Quantum mechanics: The gentle cooling touch of light. PMID- 21979045 TI - Persistence of soil organic matter as an ecosystem property. AB - Globally, soil organic matter (SOM) contains more than three times as much carbon as either the atmosphere or terrestrial vegetation. Yet it remains largely unknown why some SOM persists for millennia whereas other SOM decomposes readily- and this limits our ability to predict how soils will respond to climate change. Recent analytical and experimental advances have demonstrated that molecular structure alone does not control SOM stability: in fact, environmental and biological controls predominate. Here we propose ways to include this understanding in a new generation of experiments and soil carbon models, thereby improving predictions of the SOM response to global warming. PMID- 21979046 TI - Human oocytes reprogram somatic cells to a pluripotent state. AB - The exchange of the oocyte's genome with the genome of a somatic cell, followed by the derivation of pluripotent stem cells, could enable the generation of specific cells affected in degenerative human diseases. Such cells, carrying the patient's genome, might be useful for cell replacement. Here we report that the development of human oocytes after genome exchange arrests at late cleavage stages in association with transcriptional abnormalities. In contrast, if the oocyte genome is not removed and the somatic cell genome is merely added, the resultant triploid cells develop to the blastocyst stage. Stem cell lines derived from these blastocysts differentiate into cell types of all three germ layers, and a pluripotent gene expression program is established on the genome derived from the somatic cell. This result demonstrates the feasibility of reprogramming human cells using oocytes and identifies removal of the oocyte genome as the primary cause of developmental failure after genome exchange. PMID- 21979048 TI - Resonances arising from hydrodynamic memory in Brownian motion. AB - Observation of the Brownian motion of a small probe interacting with its environment provides one of the main strategies for characterizing soft matter. Essentially, two counteracting forces govern the motion of the Brownian particle. First, the particle is driven by rapid collisions with the surrounding solvent molecules, referred to as thermal noise. Second, the friction between the particle and the viscous solvent damps its motion. Conventionally, the thermal force is assumed to be random and characterized by a Gaussian white noise spectrum. The friction is assumed to be given by the Stokes drag, suggesting that motion is overdamped at long times in particle tracking experiments, when inertia becomes negligible. However, as the particle receives momentum from the fluctuating fluid molecules, it also displaces the fluid in its immediate vicinity. The entrained fluid acts back on the particle and gives rise to long range correlations. This hydrodynamic 'memory' translates to thermal forces, which have a coloured, that is, non-white, noise spectrum. One hundred years after Perrin's pioneering experiments on Brownian motion, direct experimental observation of this colour is still elusive. Here we measure the spectrum of thermal noise by confining the Brownian fluctuations of a microsphere in a strong optical trap. We show that hydrodynamic correlations result in a resonant peak in the power spectral density of the sphere's positional fluctuations, in strong contrast to overdamped systems. Furthermore, we demonstrate different strategies to achieve peak amplification. By analogy with microcantilever-based sensors, our results reveal that the particle-fluid-trap system can be considered a nanomechanical resonator in which the intrinsic hydrodynamic backflow enhances resonance. Therefore, instead of being treated as a disturbance, details in thermal noise could be exploited for the development of new types of sensor and particle-based assay in lab-on-a-chip applications. PMID- 21979047 TI - Complement factor H binds malondialdehyde epitopes and protects from oxidative stress. AB - Oxidative stress and enhanced lipid peroxidation are linked to many chronic inflammatory diseases, including age-related macular degeneration (AMD). AMD is the leading cause of blindness in Western societies, but its aetiology remains largely unknown. Malondialdehyde (MDA) is a common lipid peroxidation product that accumulates in many pathophysiological processes, including AMD. Here we identify complement factor H (CFH) as a major MDA-binding protein that can block both the uptake of MDA-modified proteins by macrophages and MDA-induced proinflammatory effects in vivo in mice. The CFH polymorphism H402, which is strongly associated with AMD, markedly reduces the ability of CFH to bind MDA, indicating a causal link to disease aetiology. Our findings provide important mechanistic insights into innate immune responses to oxidative stress, which may be exploited in the prevention of and therapy for AMD and other chronic inflammatory diseases. PMID- 21979049 TI - Laser cooling of a nanomechanical oscillator into its quantum ground state. AB - The simple mechanical oscillator, canonically consisting of a coupled mass-spring system, is used in a wide variety of sensitive measurements, including the detection of weak forces and small masses. On the one hand, a classical oscillator has a well-defined amplitude of motion; a quantum oscillator, on the other hand, has a lowest-energy state, or ground state, with a finite-amplitude uncertainty corresponding to zero-point motion. On the macroscopic scale of our everyday experience, owing to interactions with its highly fluctuating thermal environment a mechanical oscillator is filled with many energy quanta and its quantum nature is all but hidden. Recently, in experiments performed at temperatures of a few hundredths of a kelvin, engineered nanomechanical resonators coupled to electrical circuits have been measured to be oscillating in their quantum ground state. These experiments, in addition to providing a glimpse into the underlying quantum behaviour of mesoscopic systems consisting of billions of atoms, represent the initial steps towards the use of mechanical devices as tools for quantum metrology or as a means of coupling hybrid quantum systems. Here we report the development of a coupled, nanoscale optical and mechanical resonator formed in a silicon microchip, in which radiation pressure from a laser is used to cool the mechanical motion down to its quantum ground state (reaching an average phonon occupancy number of 0.85 +/- 0.08). This cooling is realized at an environmental temperature of 20 K, roughly one thousand times larger than in previous experiments and paves the way for optical control of mesoscale mechanical oscillators in the quantum regime. PMID- 21979050 TI - A carbon isotope challenge to the snowball Earth. AB - The snowball Earth hypothesis postulates that the planet was entirely covered by ice for millions of years in the Neoproterozoic era, in a self-enhanced glaciation caused by the high albedo of the ice-covered planet. In a hard snowball picture, the subsequent rapid unfreezing resulted from an ultra greenhouse event attributed to the buildup of volcanic carbon dioxide (CO(2)) during glaciation. High partial pressures of atmospheric CO(2) (pCO2; from 20,000 to 90,000 p.p.m.v.) in the aftermath of the Marinoan glaciation (~635 Myr ago) have been inferred from both boron and triple oxygen isotopes. These pCO2 values are 50 to 225 times higher than present-day levels. Here, we re-evaluate these estimates using paired carbon isotopic data for carbonate layers that cap Neoproterozoic glacial deposits and are considered to record post-glacial sea level rise. The new data reported here for Brazilian cap carbonates, together with previous ones for time-equivalent units, provide estimates lower than 3,200 p.p.m.v.--and possibly as low as the current value of ~400 p.p.m.v. Our new constraint, and our re-interpretation of the boron and triple oxygen isotope data, provide a completely different picture of the late Neoproterozoic environment, with low atmospheric concentrations of carbon dioxide and oxygen that are inconsistent with a hard-snowball Earth. PMID- 21979052 TI - Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model. AB - Spinal muscular atrophy (SMA) is a motor neuron disease and the leading genetic cause of infant mortality; it results from loss-of-function mutations in the survival motor neuron 1 (SMN1) gene. Humans have a paralogue, SMN2, whose exon 7 is predominantly skipped, but the limited amount of functional, full-length SMN protein expressed from SMN2 cannot fully compensate for a lack of SMN1. SMN is important for the biogenesis of spliceosomal small nuclear ribonucleoprotein particles, but downstream splicing targets involved in pathogenesis remain elusive. There is no effective SMA treatment, but SMN restoration in spinal cord motor neurons is thought to be necessary and sufficient. Non-central nervous system (CNS) pathologies, including cardiovascular defects, were recently reported in severe SMA mouse models and patients, reflecting autonomic dysfunction or direct effects in cardiac tissues. Here we compared systemic versus CNS restoration of SMN in a severe mouse model. We used an antisense oligonucleotide (ASO), ASO-10-27, that effectively corrects SMN2 splicing and restores SMN expression in motor neurons after intracerebroventricular injection. Systemic administration of ASO-10-27 to neonates robustly rescued severe SMA mice, much more effectively than intracerebroventricular administration; subcutaneous injections extended the median lifespan by 25 fold. Furthermore, neonatal SMA mice had decreased hepatic Igfals expression, leading to a pronounced reduction in circulating insulin-like growth factor 1 (IGF1), and ASO 10-27 treatment restored IGF1 to normal levels. These results suggest that the liver is important in SMA pathogenesis, underscoring the importance of SMN in peripheral tissues, and demonstrate the efficacy of a promising drug candidate. PMID- 21979051 TI - Endonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function. AB - Left ventricular mass (LVM) is a highly heritable trait and an independent risk factor for all-cause mortality. So far, genome-wide association studies have not identified the genetic factors that underlie LVM variation, and the regulatory mechanisms for blood-pressure-independent cardiac hypertrophy remain poorly understood. Unbiased systems genetics approaches in the rat now provide a powerful complementary tool to genome-wide association studies, and we applied integrative genomics to dissect a highly replicated, blood-pressure-independent LVM locus on rat chromosome 3p. Here we identified endonuclease G (Endog), which previously was implicated in apoptosis but not hypertrophy, as the gene at the locus, and we found a loss-of-function mutation in Endog that is associated with increased LVM and impaired cardiac function. Inhibition of Endog in cultured cardiomyocytes resulted in an increase in cell size and hypertrophic biomarkers in the absence of pro-hypertrophic stimulation. Genome-wide network analysis unexpectedly implicated ENDOG in fundamental mitochondrial processes that are unrelated to apoptosis. We showed direct regulation of ENDOG by ERR-alpha and PGC1alpha (which are master regulators of mitochondrial and cardiac function), interaction of ENDOG with the mitochondrial genome and ENDOG-mediated regulation of mitochondrial mass. At baseline, the Endog-deleted mouse heart had depleted mitochondria, mitochondrial dysfunction and elevated levels of reactive oxygen species, which were associated with enlarged and steatotic cardiomyocytes. Our study has further established the link between mitochondrial dysfunction, reactive oxygen species and heart disease and has uncovered a role for Endog in maladaptive cardiac hypertrophy. PMID- 21979054 TI - Microscopy: Bright light, better labels. PMID- 21979053 TI - Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy. AB - Fukuyama muscular dystrophy (FCMD; MIM253800), one of the most common autosomal recessive disorders in Japan, was the first human disease found to result from ancestral insertion of a SINE-VNTR-Alu (SVA) retrotransposon into a causative gene. In FCMD, the SVA insertion occurs in the 3' untranslated region (UTR) of the fukutin gene. The pathogenic mechanism for FCMD is unknown, and no effective clinical treatments exist. Here we show that aberrant messenger RNA (mRNA) splicing, induced by SVA exon-trapping, underlies the molecular pathogenesis of FCMD. Quantitative mRNA analysis pinpointed a region that was missing from transcripts in patients with FCMD. This region spans part of the 3' end of the fukutin coding region, a proximal part of the 3' UTR and the SVA insertion. Correspondingly, fukutin mRNA transcripts in patients with FCMD and SVA knock-in model mice were shorter than the expected length. Sequence analysis revealed an abnormal splicing event, provoked by a strong acceptor site in SVA and a rare alternative donor site in fukutin exon 10. The resulting product truncates the fukutin carboxy (C) terminus and adds 129 amino acids encoded by the SVA. Introduction of antisense oligonucleotides (AONs) targeting the splice acceptor, the predicted exonic splicing enhancer and the intronic splicing enhancer prevented pathogenic exon-trapping by SVA in cells of patients with FCMD and model mice, rescuing normal fukutin mRNA expression and protein production. AON treatment also restored fukutin functions, including O-glycosylation of alpha dystroglycan (alpha-DG) and laminin binding by alpha-DG. Moreover, we observe exon-trapping in other SVA insertions associated with disease (hypercholesterolemia, neutral lipid storage disease) and human-specific SVA insertion in a novel gene. Thus, although splicing into SVA is known, we have discovered in human disease a role for SVA-mediated exon-trapping and demonstrated the promise of splicing modulation therapy as the first radical clinical treatment for FCMD and other SVA-mediated diseases. PMID- 21979056 TI - Energy landscapes of colloidal clusters: thermodynamics and rearrangement mechanisms. AB - New experiments involving direct observation of colloidal clusters by optical microscopy promise to deliver a wealth of new information about such systems. Calculations suggest that some of the observable properties may be predicted using a simple pairwise potential to represent the interparticle forces, but in a range of parameter space that is distinctly different from previous representations of atomic clusters. The present contribution provides some benchmark calculations and predictions of structure, thermodynamics and rearrangement mechanisms for colloidal clusters containing up to 80 particles. The results suggest that distinct features characteristic of short-ranged interactions should be observable in terms of the structure, thermodynamics and dynamical properties. Analysis of a kinetic transition network for the 19 particle cluster reveals super-Arrhenius behaviour in the dynamics, analogous to a 'fragile' glass-former. PMID- 21979057 TI - Electrosynthesis of cyclic carbonates from epoxides and atmospheric pressure carbon dioxide. AB - The use of CO(2) for the preparation of value-added compounds has dramatically increased due to increased global warming concerns. We herein report an electrochemical cell containing a copper cathode and a magnesium anode that effectively converts epoxides and carbon dioxide to cyclic carbonates under mild electrochemical conditions at atmospheric pressure. PMID- 21979058 TI - Cellular immunity, low-density lipoprotein and atherosclerosis: break of tolerance in the artery wall. AB - Atherosclerosis is a chronic inflammatory disease. Atherosclerotic plaques contain abundant immune cells that can dictate and effect inflammatory responses. Among them, T cells are present during all stages of the disease suggesting that they are essential in the initiation as well as the progression of plaque. Experimental as well as clinical research has demonstrated different T cell subsets, i.e. CD4+ Th1, Th2, Th17, and Treg as well as CD8+ and NKT cells in the plaque. Moreover, candidate antigens inducing T cell responses have been identified. Knowledge about the pathological role of these cells in atherogenesis may lead to development of new therapies. This review provides an overview of the research field of cellular immunity in atherosclerosis. It emphasises the events and findings involving antigen specific T cells, in particular low-density lipoprotein-specific T cells. PMID- 21979059 TI - Yeast thioredoxin-enriched extracts for mitigating the allergenicity of foods. AB - Thioredoxin (TRX) catalyzes the reduction of disulfide bonds in proteins via the NADPH-dependent thioredoxin reductase system. Reducing the disulfide bonds of allergenic proteins in food by TRX lowers the allergenicity. We established in this study a method to prepare TRX-enriched extracts from the edible yeast, Saccharomyces cerevisiae, on a large and practical scale, with the objective of developing TRX-containing functional foods to mitigate food allergy. Treating with the yeast TRX-enriched extracts together with NADPH and yeast thioredoxin reductase enhanced the pepsin cleavage of beta-lactoglobulin and ovomucoid (OM). We also examined whether yeast TRX can mitigate the allergenicity of OM by conducting immediate allergy tests on guinea pigs. The treatment with TRX reduced the anaphylactic symptoms induced by OM in these tests. These results indicate that yeast TRX was beneficial against food allergy, raising the possibility that yeast TRX-enriched extracts can be applied to food materials for mitigating food allergy. PMID- 21979060 TI - Optimal reaction conditions for the production of gamma-aminobutyric acid by the marine yeast isolate Pichia anomala MR-1 strain. AB - The optimal conditions for the production of gamma-aminobutyric acid (GABA) by the marine yeast isolate Pichia anomala MR-1 strain appeared to be completely different from those required for growth and biomass production of the yeast strain. By proper reaction temperatures and pH levels, the efficiency of GABA production was improved dramatically. Supplying enough energy for the reaction was another important technical element to improve the production efficiency of GABA. The MR-1 isolate was found to use various saccharides, including glucose and fructose, as well as intermediate metabolites in the tricarboxylic acid (TCA) cycle to promote GABA production. On the other hand, ethanol, various free amino acids, and organic acids were detected along with GABA in the reaction solution. These results suggest that production of GABA by the MR-1 strain is not due to a single enzymatic reaction. Rather it is a fermentation reaction, possibly involving a combination of intracellular metabolic pathways. PMID- 21979061 TI - Dietary vitamin E deficiency increases anxiety-like behavior in juvenile and adult rats. AB - Vitamin E deficiency from birth or infancy has recently been found to increase anxiety-like behavior in rodents. The present study was undertaken to elucidate the effect of dietary vitamin E deficiency on anxiety in adult rats in comparison with juvenile rats. Male Wistar rats, 3 or 10 weeks old, were divided into two groups and fed a control or vitamin E-deficient diet for 4 weeks. The results of behavioral analysis revealed that vitamin E-deficiency increased anxiety in both juvenile and adult rats. Plasma, liver, and brain alpha-tocopherol concentrations decreased significantly due to vitamin E deficiency in both age groups. Plasma corticosterone concentrations were higher in the vitamin E-deficient rats in response to the stress of a behavioral test. Based on these results, we conclude that dietary vitamin-E deficiency induces anxiety in adult rats as well as juvenile rats. This might be due to an elevated plasma corticosterone concentration. PMID- 21979062 TI - Stimulating macrophage activity in mice and humans by oral administration of quillaja saponin. AB - Quillaja saponin (QS) was examined for its immunostimulating effect on mice and humans after oral administration. Mice fed QS for 24 h significantly increased in chemotactic and phagocytosis activities of peritoneal macrophages. This enhancing effect in both activities continued for 4-d after QS administration. Mice fed QS for 24 h prior to an interperitoneal challenge with Escherichia coli showed a higher survival rate than the control group. Peripheral blood analysis of volunteers showed significant increases in chemotactic and phagocytosis activities after oral administration of QS for 7 d. Furthermore, the volunteers did not show significant changes in immunoglobulin, transaminase, IL-1alpha, or TNF-alpha levels, or in serum albumin concentrations. Thus orally administered QS can effectively enhance the immune response through stimulation of macrophages without adverse effects. PMID- 21979063 TI - A truncated form of SpoT, including the ACT domain, inhibits the production of cyclic lipopeptide arthrofactin, and is associated with moderate elevation of guanosine 3',5'-bispyrophosphate level in Pseudomonas sp. MIS38. AB - Arthrofactin is a biosurfactant produced by Pseudomonas sp. MIS38. We have reported that transposon insertion into spoT (spoT::Tn5) causes moderate accumulation of guanosine 3',5'-bispyrophosphate (ppGpp) and abrogates arthrofactin production. To analyze the linkage of SpoT function and ablation of arthrofactin production, we examined the spoT::Tn5 mutation. The results showed that spoT::Tn5 is not a null mutation, but encodes separate segments of SpoT. Deletion of the 3' region of spoT increased the level of arthrofactin production, suggesting that the C-terminal region of SpoT plays a suppressive role. We evaluated the expression of a distinct segment of SpoT. Forced expression of the C-terminal region that contains the ACT domain resulted in the accumulation of ppGpp and abrogated arthrofactin production. Expression of the C-terminal segment also reduced MIS38 swarming and resulted in extensive biofilm formation, which constitutes the phenocopy of the spoT::Tn5 mutant. PMID- 21979064 TI - Purification and characterization of levansucrases from Bacillus amyloliquefaciens in intra- and extracellular forms useful for the synthesis of levan and fructooligosaccharides. AB - The intra- and extracellular levansucrase (LS) activities produced by Bacillus amyloliquefaciens were promoted by supplementing the sucrose medium with yeast and peptone as nitrogen sources. These activities were purified by polyethylene glycol (PEG) fractionation for the first time. PEGs of low molecular weight selectively fractionated the intracellular LS activity rather than the extracellular LS activity. Contrary to other LSs, B. amyloliquefaciens LSs exhibited high levan-forming activity over a wide range of sucrose concentrations. The optimum temperatures for the intra- (25-30 degrees C) and extracellular (40 degrees C) LS transfructosylation activities were lower than those for the hydrolytic activities (45-50 degrees C; 50 degrees C). In addition, the catalytic efficiency for the transfructosylation activity of intracellular LS was higher than that of extracellular LS. These differences between intra- and extracellular LSs reveal the occurrence of certain conformational changes to LS upon protein secretion and/or purification. This study is the first to highlight that B. amyloliquefaciens LSs synthesized a variety of FOSs from various saccharides, with lactose and maltose being the best fructosyl acceptors. PMID- 21979065 TI - Enzymatic sulfation of tocopherols and tocopherol metabolites by human cytosolic sulfotransferases. AB - Tocopherols are essential micronutrients for mammals widely known as potent lipid soluble antioxidants that are present in cell membranes. Recent studies have demonstrated that most of the carboxychromanol (CEHC), a tocopherol metabolite, in the plasma exists primarily in sulfate- and glucuronide-conjugated forms. To gain insight into the enzymatic sulfation of tocopherols and their metabolites, a systematic investigation was performed using all 14 known human cytosolic sulfotransferases (SULTs). The results showed that the members of the SULT1 family displayed stronger sulfating activities toward tocopherols and their metabolites. These enzymes showed a substrate preference for gamma-tocopherol over alpha-tocopherol and for gamma-CEHC over other CEHCs. Using A549 human lung epithelial cells in a metabolic labeling study, a similar trend in the sulfation of tocopherols and CEHCs was observed. Collectively, the results obtained indicate that SULT-mediated enzymatic sulfation of tocopherols and their metabolites is a significant pathway for regulation of the homeostasis and physiological functions of these important compounds. PMID- 21979066 TI - A Prunus mume extract stimulated the proliferation and differentiation of osteoblastic MC3T3-E1 cells. AB - Osteoporosis is a serious disease caused by decreased bone mass. There is constant matrix remodeling in bones, by which bone formation is performed by osteoblastic cells, whereas bone resorption is accomplished by osteoclast cells. We investigated the effect of a Japanese apricot (Prunus mume SIBE. et ZUCC.) extract on the proliferation and osteoblastic differentiation in pre-osteoblastic MC3T3-E1 cells. An alkaline phosphatase (ALP) activity assay, cell proliferation assay, alizarin red staining and expression analysis of osteoblastic genes were carried out to assess the proliferation and osteoblastic differentiation. The water-soluble fraction of Prunus mume (PWF) increased the ALP activity, cell proliferation and mineralization. The gene expression of osteopontin and bone morphogenetic protein-2, which are markers in the early period of osteoblastic differentiation, were significantly enhanced by the PWF treatment. PWF therefore stimulated the proliferation and osteoblastic differentiation of cells and may have potential to prevent osteoporosis. PMID- 21979067 TI - Triglyceride with medium-chain fatty acids increases the activity and expression of hormone-sensitive lipase in white adipose tissue of C57BL/6J mice. AB - We have previously shown that medium-chain triglyceride (MCT) resulted in significantly less body fat mass than long-chain triglyceride (LCT) did in hypertriglyceridimic subjects. The possible mechanism for this was investigated by measuring and analyzing changes in the body fat, blood lipid profile, enzymatic level and activity of hormone-sensitive lipase (HSL) and its mRNA expression, and levels of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in white adipose tissue (WAT) of C57BL/6J mice fed for 16 weeks on an MCT or LCT diet. MCT induced lower body weight and body fat, and an improved blood lipid profile than LCT did. The enzymatic level and activity of HSL and its mRNA expression, and the levels of cAMP and PKA were significantly higher in WAT of mice fed with the MCT diet. No significant differences in the levels of lipoprotein lipase and peroxisome proliferator-activated receptor-gamma in WAT were apparent between the effects of MCT and LCT. It is concluded that lipolysis by the increased level and activity of HSL, which was induced by the activation of cAMP-dependent PKA in WAT, was partially responsible for the lower fat accumulation in C57BL/6J mice fed with MCT. PMID- 21979068 TI - High cadmium-binding ability of a novel Colocasia esculenta metallothionein increases cadmium tolerance in Escherichia coli and tobacco. AB - Experimental evidence in vivo as to the functional roles and binding properties to cadmium (Cd) of type-2 plants metallothionein (MT) has been limited thus far. We investigated the biological role of metallothionein from Colocasia esculenta (CeMT2b) in Escherichia coli and tobacco, and developed a new model for the relationship between Cd tolerance and Cd-binding ability. Heterologous expression of CeMT2b in Escherichia coli greatly enhanced Cd tolerance and accumulated Cd content as compared to control cells. The molecular weight of CeMT2b increased with Cd, and CeMT2b bound up to 5.96+/-1 molar ratio (Cd/protein). Under Cd stress, transgenic tobacco plants displayed much better seedling growth and high Cd accumulation than the wild type. The presence of an extra CXC motif in CeMT2b contributed to the enhanced Cd-tolerance. The present study provides the first insight into the ability of type-2 plant MT to bind physiological Cd. PMID- 21979069 TI - Antimicrobial, antioxidant, and anti-inflammatory activities of essential oils from five selected herbs. AB - Eucalyptus bridgesiana, Cymbopogon martinii, Thymus vulgaris, Lindernia anagallis, and Pelargonium fragrans are five species of herbs used in Asia. Their essential oils were analyzed by GC-MS, and a total of 36 components were detected. The results of our study indicated that, except for the essential oil of P. fragrans, all of the essential oils demonstrated obvious antimicrobial activity against a broad range of microorganisms. The C. martinii essential oil, which is rich in geraniol, was the most effective antimicrobial additive. All of the essential oils demonstrated antioxidant activities on 2,2-diphenyl-1 picrylhydrazyl radical scavenging assay, beta-carotene/linoleic acid assay, and nitric oxide radical scavenging assay. Furthermore, the T. vulgaris essential oil, which possesses plentiful thymol, exhibited the highest antioxidant activity. For P. acnes-induced secretion of pro-inflammatory cytokines, the essential oils of P. aeruginosa, C. martinii, and T. vulgaris reduced the TNF alpha, IL-1beta, and IL-8 secretion levels of THP-1 cells. PMID- 21979070 TI - Effects of methoxsalen from Poncirus trifoliata on acetylcholinesterase and trimethyltin-induced learning and memory impairment. AB - Previously, we identified methoxsalen (8-methoxy-2',3',6,7-furocoumarin) as the bioactive compound probably responsible for acetylcholinesterase (AchE) inhibition achieved by feeding crude extract of Poncirus trifoliate. To confirm the activity of methoxsalen, Institute of Cancer Research (ICR) mice were fed a control or a methoxsalen-supplemented diet for 4 weeks, and then learning and memory enhancing effects with respect to trimethyltin (TMT)-induced neurotoxicity were evaluated. The brain tissues of ICR mice were dissected after completion of the behavioral tests for biochemical analysis. Methoxsalen effectively reversed TMT-induced memory impairment on both Y-maze and passive avoidance tests. Brain AchE activity was inhibited by the oral consumption of all concentrations of methoxsalen. Moreover, the level of oxidative stress was significantly ameliorated in the groups on methodsalen containing diets. This is the first in vivo study conducted with methoxsalen in the field of AD research, and it indicates that further investigation of methoxsalen is warranted. PMID- 21979071 TI - Fermented barley extract supplementation maintained antioxidative defense suppressing lipopolysaccharide-induced inflammatory liver injury in rats. AB - Utilizing phytochemicals in treating inflammation is becoming a viable alternative to pharmacological treatment. We have reported that fermented barley extract (FBE) effectively suppresses oxidative stress in chronically ethanol-fed rats. Here we report that FBE suppressed acute increases in oxidative stress as a response to lipopolysaccharide (LPS)-induced inflammation. Rats supplemented with FBE for 10 d showed decreases in plasma interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha by 25%, 34%, and 35% respectively after LPS challenge. Liver damage was significantly suppressed, as marked by a 44% decrease in plasma alanine aminotransferase. FBE supplementation sustained liver anti-oxidative enzymes, catalase, glutathione peroxidase, and superoxide dismutase, at transcriptional and enzymatic levels, thus suppressing oxidative stress markers such as plasma nitric oxide and 8-hydroxy-2'-deoxyguanosine, by 42% and 23% respectively. We concluded that active compounds in FBE effectively inhibited the propagation of inflammation by suppressing oxidative stress. PMID- 21979072 TI - Purification and characterization of a thermostable xylanase from Saccharopolyspora pathumthaniensis S582 isolated from the gut of a termite. AB - An extracellular thermostable xylanase produced by Saccharopolyspora pathumthaniensis S582 was purified 167-fold to homogeneity with a recovery yield of 12%. The purified xylanase appeared as a single protein band on SDS-PAGE, with a molecular mass of 36 kDa. The optimal temperature and pH of the xylanase were 70 degrees C and 6.5. The enzyme was stable within a pH range of 5.5-10.0. It retained its activity after incubation at 50 degrees C for 2 h. Its half lives at temperatures of 60 and 70 degrees C were 180 and 120 min respectively. Hydrolysis of beechwood xylan by the xylanase yielded xylobiose and xylose as major products. The enzyme acted specifically on xylan as an endo-type xylanase, and exhibited a K(m) value of 3.92 mg/mL and a V(max) value of 256 umol/min/mg. Enzyme activity was completely inhibited by Hg(2+), and was stimulated by Rb(+) and Cs(+). The xylanase gene was cloned from genomic DNA of Saccharopolyspora pathumthaniensis S582 and sequenced. The ORF consisted of 1,107 bp and encoded 368 amino acid residues containing a putative signal peptide of 23 residues. This xylanase is a new member of family (GH) 10 that shows highest identity, of 63.4%, with a putative xylanase from Nocardiopsis dassonvillei subsp. dassonvillei. PMID- 21979073 TI - A glycan of Psi-factor from Dictyostelium discoideum contains a bisecting-GlcNAc, an intersecting-GlcNAc, and a core alpha-1,6-fucose. AB - A secretory glycoprotein named Psi-factor that we have purified and cloned from Dictyostelium discoideum is prespore cell-inducing factor. To address its functional significance, it is necessary to examine the attached sites and structures of its glycans as well as its protein structure. Here we identified and isolated a tryptic glycosylated peptide with the 71st to 89th amino acids of Psi-factor that contained the consensus amino acid sequence for an N-linked glycan (N-T-T). MALDI-TOF mass spectrometry indicated that the major protonated molecular ions, [M+H](+), of the glycopeptide were present at m/z 3,806, the minor m/z 3,603 and 3,400 ions corresponding to the loss of one and two N acetylhexosamines respectively. Digestion of it with N-glycosidase F gave a molecular mass of 1,766.9 for the whole glycan moiety, which accounts for its composition of five hexoses, four N-acetylhexosamines, and a deoxyhexose. Further digestion experiments on the basis of the substrate specificity of alpha mannosidase and beta-N-acetylhexosaminidase allowed us to elucidate the unique structure of the glycan, which contains a bisecting and an intersecting GlcNAc and a core alpha1,6-fucosyl moiety. PMID- 21979074 TI - The effect of low-pressure carbonation on the heat inactivation of Escherichia coli. AB - The heat inactivating effect of low-pressure carbonation (LPC) at 1 MPa against Escherichia coli was enhanced to 3.5log orders. This study aimed to investigate the mechanisms of this increase in heat inactivation efficiency. The increased inactivation ratio was found to be the result of LPC-induced heat sensitization. This sensitization was not due to any physical damage to the cells as a result of the treatment. Following the depletion of intracellular ATP, the failure of the cells to discard protons caused an abnormal decrease in the intracellular pH. However, in the presence of glucose, the inactivation ratio decreased. In addition, a further increase in inactivation of more than 2log orders occurred in the presence of the protein synthesis inhibitor chloramphenicol. Hence, the decreased heat resistance of E. coli under LPC was most likely due to a depletion of intracellular ATP and a decreased capacity for protein synthesis. PMID- 21979075 TI - Global analysis of the genes involved in the thermotolerance mechanism of thermotolerant Acetobacter tropicalis SKU1100. AB - Acetobacter tropicalis SKU1100 is a thermotolerant acetic acid bacterium that grows even at 42 degrees C, a much higher temperature than the limit for the growth of mesophilic strains. To elucidate the mechanism underlying the thermotolerance of this strain, we attempted to identify the genes essential for growth at high temperature by transposon (Tn10) mutagenesis followed by gene or genome analysis. Among the 4,000 Tn10-inserted mutants obtained, 32 exhibited a growth phenotype comparable to that of the parent strain at 30 degrees C but not at higher temperatures. We identified the insertion site of Tn10 on the chromosomes of all the mutant strains by TAIL (Thermal Asymmetric Interlaced) PCR, and found 24 genes responsible for thermotolerance. The results also revealed a partial overlap between the genes required for thermotolerance and those required for acetic acid resistance. In addition, the origin and role of these thermotolerant genes are discussed. PMID- 21979076 TI - Ethanol production from xylose by a recombinant Candida utilis strain expressing protein-engineered xylose reductase and xylitol dehydrogenase. AB - The industrial yeast Candida utilis can grow on media containing xylose as sole carbon source, but cannot ferment it to ethanol. The deficiency might be due to the low activity of NADPH-preferring xylose reductase (XR) and NAD(+)-dependent xylitol dehydogenase (XDH), which convert xylose to xylulose, because C. utilis can ferment xylulose. We introduced multiple site-directed mutations in the coenzyme binding sites of XR and XDH derived from the xylose-fermenting yeast Candida shehatae to alter their coenzyme specificities. Several combinations of recombinant and native XRs and XDHs were tested. Highest productivity was observed in a strain expressing CsheXR K275R/N277D (NADH-preferring) and native CsheXDH (NAD(+)-dependent), which produced 17.4 g/L of ethanol from 50 g/L of xylose in 20 h. Analysis of the genes responsible for ethanol production from the xylose capacity of C. utilis indicated that the introduction of CsheXDH was essential, while overexpression of CsheXR K275R/N277D improved efficiency of ethanol production. PMID- 21979077 TI - Light-responsive double B-box containing transcription factors are conserved in Physcomitrella patens. AB - In the model seed plant Arabidopsis thaliana, a sub-family of B-box containing transcriptional factors (BBXs), which is classified in the BBX-IV group based on the domain structure, contains two tandem B-box domains and plays crucial roles in early photomorphogenesis under the control of blue light receptors, cry1 and cry2. The results of an examination of light responsiveness of representative Physcomitrella BBX-IV genes and their heterologous expression in Arabidopsis suggested that the light signaling-related characteristics of the BBX-IV subfamily are evolutionarily conserved in a moss, which is a basal lineage of land plants. PMID- 21979078 TI - Non-synonymous SNP in the ApoR gene associated with pork meat quality. AB - Two novel non-synonymous SNPs in the 2nd and 3rd exons of the porcine ApoR gene are reported. One was identified as a novel SNP significantly associated with multiple traits of pork meat quality. The data can provide a useful resource for developing a marker in the genetic improvement of pigs. PMID- 21979079 TI - In vitro fluorescent analysis of preprotein import into chloroplasts. AB - Despite recent progress in fluorescence techniques employed to observe protein localization in living cells, the in vitro chloroplastic protein transport assay remains a useful tool for determining the destinations of proteins. Although an in vitro synthesized, radiolabeled precursor protein is frequently used as the transport substrate, we have developed a transport assay system with a non radiolabeled precursor protein that carries an epitope tag and is overexpressed in Escherichia coli. Thus, a transported protein can be detected by immunoblotting (Inoue et al., Plant Physiol. Biochem., 46, 541-549 (2008)). Here, we propose another in vitro protein transport system that combines fluorescence techniques. We attempted to use two types of precursors: a green fluorescent protein (GFP)-fused precursor and a fluorescent dye-labeled one. Both were successfully imported into chloroplasts. However, the fluorescent dye-labeled precursor was more advantageous than the GFP-fused precursor in the in vitro system. PMID- 21979080 TI - Amyloid beta induces adhesion of erythrocytes to endothelial cells and affects endothelial viability and functionality. AB - It has been suggested that amyloid beta-peptide (Abeta) might mediate the adhesion of erythrocytes to the endothelium which could disrupt the properties of endothelial cells. We provide evidence here that Abeta actually induced the binding of erythrocytes to endothelial cells and decreased endothelial viability, perhaps by the generation of oxidative and inflammatory stress. These changes are likely to contribute to the pathogenesis of Alzheimer's disease. PMID- 21979081 TI - The roles of CATALASE2 in abscisic acid signaling in Arabidopsis guard cells. AB - We investigated the roles of catalase (CAT) in abscisic acid (ABA)-induced stomatal closure using a cat2 mutant and an inhibitor of CAT, 3-aminotriazole (AT). Constitutive reactive oxygen species (ROS) accumulation due to the CAT2 mutation and AT treatment did not affect stomatal aperture in the absence of ABA, whereas ABA-induced stomatal closure, ROS production, and [Ca(2+)](cyt) oscillation were enhanced. PMID- 21979082 TI - Cloning and characterization of catalases from rice, Oryza sativa L. AB - Catalase is the major H(2)O(2)-scavenging enzyme in all aerobic organisms. From the cDNA sequences of three rice (Oryza sativa L.) genes that encode for predicted catalases (OsCatA, OsCatB, and OsCatC), complete ORFs were subcloned into pET21a and expressed as (His)(6)-tagged proteins in Escherichia coli. The recombinant (His)(6)-polypeptides were enriched to apparent homogeneity and characterized. With H(2)O(2) as substrate, the highest catalase k(cat) value (20+/-1.71*10(-3) min(-1)) was found in recombinant OsCatB. The optimum temperatures for catalase activity were 30 degrees C for OsCatA and OsCatC and 25 degrees C for OsCatB, while the pH optima were 8.0, 7.5, and 7.0 for OsCatA, OsCatB, and OsCatC respectively. All the catalases were inhibited by sodium azide, beta-mercaptoethanol, and potassium cyanide, but only weakly by 3-amino 1,2,4-triazole. The various catalases exhibited different catalase activities in the presence of different salts at different concentrations, OsCatC showing higher salt inhibitory effects than the two other OsCats. PMID- 21979083 TI - Properties of a high malic acid-producing strains of Saccharomyces cerevisiae isolated from sake mash. AB - We characterized high malic acid-producing strains of Saccharomyces cerevisiae isolated from sake mash. We compared the gene expression of these strains with those of the parental strain by DNA microarray, and found that stress response genes, such as HSP12, were commonly upregulated in the high malate-producing strains, whereas thiamine synthesis genes, such as THI4 and SNZ2, were downregulated in these strains. PMID- 21979084 TI - Massilia sp. BS-1, a novel violacein-producing bacterium isolated from soil. AB - A novel bacterium, Massilia sp. BS-1, producing violacein and deoxyviolacein was isolated from a soil sample collected from Akita Prefecture, Japan. The 16S ribosomal DNA of strain BS-1 displayed 93% homology with its nearest violacein producing neighbor, Janthinobacterium lividum. Strain BS-1 grew well in a synthetic medium, but required both L-tryptophan and a small amount of L histidine to produce violacein. PMID- 21979085 TI - Effects of a plum (Prunus mume Siebold and Zucc.) ethanol extract on the immune system in vivo and in vitro. AB - The effect of a plum ethanol extract (PEE) on immunity was analyzed. An oral administration of PEE increased the interleukin (IL)-12p40 concentration in the serum and T-cell ratio in the spleen. In vitro studies revealed that PEE stimulated IL-12p70 production in peritoneal macrophages and natural killer activity. These findings suggest that PEE enhanced the immune function by stimulating innate immune cells. PMID- 21979086 TI - Novel 4,5-dihydro-thiazinogeldanamycin in a gdmP mutant strain of Streptomyces hygroscopicus 17997. AB - Novel geldanamycin derivative, 4,5-dihydro-thiazinogeldanamycin (3), was characterized from the gdmP mutant in Streptomyces hygroscopicus 17997, besides expected 4,5-dihydro-geldanamycin (2). The presence of this compound would suggest an unknown post-PKS modification in geldanamycin biosynthesis. Compound 3 exhibited moderate anti-HSV-1-virus activity and higher water solubility than geldanamycin (1). Cysteine served as a precursor to synthesize 3, whose formation required obligatory enzymatic assistance. PMID- 21979087 TI - WITHDRAWN:Hydrodynamic Studies of Human AIF-M2 Protein in Solution. AB - Ahead of Print article withdrawn by publisher. Human apoptosis-inducing factor 2 (AIF-M2, also called AMID) is a flavoprotein oxidoreductase that contains modified flavin 6-hydroxy-FAD. Unlike most apparent flavoproteins, AIF-M2 has DNA binding activity that leads to caspase-independent apoptosis. Although the oxidoreductase and DNA-binding activity of AIF-M2 have been confirmed, the relevance of oxidoreductase activity and DNA-binding activity require consideration. In this study, we used hydrodynamic and kinetic methods to investigate the protein conformational state during the execution of oxidoreductase activity and pro-apoptosis (DNA-binding activity). Results indicated that DNA binding to AIF-M2 resulted in a remarkable conformational change in AIF-M2. It was also found that execution of physiological functions (e.g., oxidoreductase and DNA binding activity) of AIF-M2 required a unique conformation in solution. Our data indicate that the presence of pyridine nucleotide prevents the binding of AIF-M2 to DNA. Based on these results, we suggest that the cellular pyridine nucleotide plays an important role at the onset of apoptosis induced by AIF-M2. PMID- 21979088 TI - Turnover ability of a designed RNA acting as a template for chemical peptide ligation. AB - A designed self-folding RNA possessing two peptide-recognition motifs served as a template for the chemical ligation of two RNA-binding peptides under stoichiometric conditions. In this study, we investigated the turnover ability of this template RNA in facilitation of peptide ligation and found that the RNA exhibited modest turnover ability under conditions in which its 3D structure was marginally stable. PMID- 21979089 TI - Urakunoside, a new tetraglycosyl kaempferol from petals of the Wabisuke camellia cv. Tarokaja. AB - A new tetraglycosyl flavonol, 3-O-[2-O-xylosyl-6-O-(3-O-glucosyl-rhamnosyl) glucosyl] kaempferol was isolated from pale purplish-pink petals of Wabisuke camellia cv. Tarokaja with three known flavonols. It was named urakunoside after the species name of Tarokaja, Camellia uraku. Urakunoside was a major flavonol component in the Tarokaja petals, but was not detected in petals of Tarokaja's presumed ancestor species. PMID- 21979090 TI - A novel soluble beta-glucan salecan protects against acute alcohol-induced hepatotoxicity in mice. AB - This investigation was designed to determine the effect of a novel soluble beta glucan salecan on acute alcohol-induced hepatic injury in mice. Mice were given salecan (15 or 30 mg/kg) or PBS for 4 d. Ethanol (6 g/kg) was administered orally 1 h after the last injection. The animals were sacrificed at 10 h after alcohol administration. Pretreatment with salecan significantly ameliorated the hepatic damage induced by ethanol, as evidenced by markedly reduced serum aminotransferase activities and hepatocyte steatosis. Salecan administration remarkably alleviated the formation of thiobarbituric acid-reactive substances and counteracted glutathione depletion. The mRNA level of peroxisome proliferator activated receptor alpha, a major gene responsible for fatty acid oxidation, was significantly increased after salecan pretreatment. The expression of diacylglycerol acyltransferase 1, an important gene responsible for triacylglycerol synthesis, was markedly decreased after salecan was administrated. These findings suggest that salecan might represent a novel protective strategy against alcoholic liver injury. PMID- 21979091 TI - Rapid and economic DNA extraction from a single salmon egg for real-time PCR amplification. AB - Salmon eggs are common in Japanese sushi and other seafood products; however, certain fish eggs are used as counterfeit salmon eggs which are found in foods and processed products. This study develops a simple, rapid, and cost-effective method for DNA extraction, filtration (FT) and dilution (DL) protocols from a single salmon egg with good DNA quality for real-time PCR amplification. The DNA amount, DNA quality, and real-time PCR performance for different dilutions and different lengths of PCR amplicons were evaluated and compared with the common Qiagen tissue kit (QTK) and Chelex-100-based (CX) protocols. The extracted DNA from a single salmon egg using the FT or DL protocol can be applied in phylogenic research, food authentication and post-marketing monitoring of genetically modified (GM) food products. PMID- 21979092 TI - Comparative study on the toxic effects of red tide flagellates Heterocapsa circularisquama and Chattonella marina on the short-necked clam (Ruditapes philippinarum). AB - Heterocapsa circularisquama showed much higher toxic effects on short-necked clams than Chattonella marina. Clams exposed to H. circularisquama exhibited morphological changes concomitant with an accumulation of mucus-like substances in the gills, a profound reduction in filtration activity, and lysosomal destabilization in hemocytes. Chattonella marina was less effective than H. circularisquama, and Heterocapsa triquetra was almost harmless in all these criteria. These results suggest that H. circularisquama exerted its lethal effect on short-necked clams through gill tissue damage and subsequent induction of physiological stress. PMID- 21979093 TI - Identification and characterization of UDP-glucose dehydrogenase from the hyperthermophilic archaon, Pyrobaculum islandicum. AB - A gene encoding a UDP-glucose dehydrogenase homologue was identified in the hyperthermophilic archaeon, Pyrobaculum islandicum. This gene was expressed in Escherichia coli, and the product was purified and characterized. The expressed enzyme is the most thermostable UDP-glucose dehydrogenase so far described, with a half-life of 10 min at 90 degrees C. The enzyme retained its full activity after incubating in a pH range of 5.0-10.0 for 10 min at 80 degrees C. The temperature dependence of the kinetic parameters for this enzyme was examined at 37-70 degrees C. A decrease in K(m)s for UDP-glucose and NAD was observed with decreasing temperature. This resulted in the enzyme still retaining high catalytic efficiency (V(max)/K(m)) for the substrate and cofactor, even at 37 degrees C. These characteristics make the enzyme potentially useful for its application at a much lower temperature such as 37 degrees C than the optimum growth temperature of 100 degrees C for P. islandicum. PMID- 21979094 TI - An assay for detecting neutralization of rotavirus infection by quantitative determination of VP6 protein fluorescence intensity. AB - Previous rotavirus infection studies used the focus reduction assay extensively to evaluate cellular responses to viral infection, but this technique has a number of limitations. In this study, we developed a simplified, accurate rotavirus infection assay to evaluate the effects of inhibitory substances on rotavirus infection in vitro by measurement of the fluorescence intensities of stained cells. PMID- 21979095 TI - Purification and characterization of Fe(III)-EDTA reductase from Bacillus sp. B 3. AB - Fe(III)-EDTA reductase was purified from Bacillus sp. B-3 isolated as a Fe(III) EDTA-degrading bacterium. The purified enzyme showed a single protein band corresponding to a molecular mass of 19 kDa on SDS-PAGE, and had FMN as cofactor. It was alkali-thermostable. Its N-terminal amino acid sequence was identical with that of NADPH azoreductase from several species of Bacillus. PMID- 21979096 TI - A marine carotenoid, fucoxanthin, induces regulatory T cells and inhibits Th17 cell differentiation in vitro. AB - Fucoxanthin is a non-provitamin A carotenoid contained in brown seaweeds. We found that it suppressed interleukin-17 secretion from CD4(+) T cells under IL-17 producing T (Th17) cell development conditions. By evaluating T cell differentiation in vitro, fucoxanthin and its metabolite fucoxanthinol inhibited T cell differentiation into Th17 cells. This suggests that fucoxanthin can improve inflammatory diseases due to Th17 cells. PMID- 21979097 TI - Elucidation of crucial structures for a catechol-based inhibitor of plasma hyaluronan-binding protein (factor VII activating protease) autoactivation. AB - Plasma hyaluronan-binding protein (PHBP) is a serine protease the activation of which is implicated in inflammation. Previous investigations have suggested the presence of catechol-binding sites in its proenzyme form, pro-PHBP. Here we found that compounds with plural catechol groups conjugated with strong electron withdrawing groups, such as tyrphostin AG 537 (IC(50)=18 nM), were potent inhibitors of pro-PHBP activation. PMID- 21979098 TI - 10T024A, a new phenazine derivative, as a radical scavenger and a prostaglandin, leukotriene release suppressor. AB - We identified a new radical scavenger, 10T024A (C(15)H(12)N(2)O(4)), from a culture of the Streptomyces sp. Spectroscopic elucidation indicated that this compound is a new phenazine derivative. 10T024A showed radical-scavenging activity with an ED(50) of 125 uM. Moreover, it showed prostaglandin D(2) (PGD(2)) and leukotriene B(4) (LTB(4)) release suppressive activity in rat basophilic leukemia (RBL-2H3) cells, at IC(50): 8 uM and 10 uM respectively. PMID- 21979099 TI - Synthesis of the disialic acid-embedded glycan part of ganglioside HPG-1. AB - Synthesis of tetrasaccharide portion of ganglioside HPG-1 is described. The tetrasaccharide sequence, Fuc-alpha(1,8)-Neu5Gc-alpha(2,4)-Neu5Ac-alpha(2,6)-Glc, was successfully assembled by a linear strategy, in which the 1,5-lactamized sialyl galactose acceptor and the 8-O-Lev-N-Troc-sialic acid donor were exploited as key units. PMID- 21979100 TI - Characterization of the nuclear- and plastid-encoded secA-homologous genes in the unicellular red alga Cyanidioschyzon merolae. AB - SecA is an ATP-driven motor for protein translocation in bacteria and plants. Mycobacteria and listeria were recently found to possess two functionally distinct secA genes. In this study, we found that Cyanidioschyzon merolae, a unicellular red alga, possessed two distinct secA-homologous genes; one encoded in the cell nucleus and the other in the plastid genome. We found that the plastid-encoded SecA homolog showed significant ATPase activity at low temperature, and that the ATPase activity of the nuclear-encoded SecA homolog showed significant activity at high temperature. We propose that the two SecA homologs play different roles in protein translocation. PMID- 21979101 TI - Complementary and alternative medicine for rheumatoid arthritis and osteoarthritis: an overview of systematic reviews. AB - This review critically evaluates the literature on complementary and alternative medicine (CAM) as treatment options for rheumatoid arthritis and osteoarthritis. DESIGN: Electronic databases were searched to identify all relevant systematic reviews of the effectiveness of CAM in rheumatoid arthritis and osteoarthritis published between January 2010 and January 2011. Reviews were defined as systematic if they included explicit and repeatable inclusion and exclusion criteria for studies. Their methodological quality was assessed using the Oxman criteria for systematic reviews. RESULTS: Five systematic reviews met our inclusion criteria. They all arrived at cautious conclusions. Four reviews were of high quality and one was burdened with high risk of bias. The evidence to support the effectiveness of CAM as a treatment option for rheumatoid arthritis and osteoarthritis is ambiguous. PMID- 21979102 TI - Absorbance of retinal oil droplets of the budgerigar: sex, spatial and plumage morph-related variation. AB - Intraspecific variation in photoreceptor physiology is known in several vertebrate taxa, but is currently unknown in birds, despite many avian traits varying intraspecifically, and avian visual ecology encompassing a wide range of environments and visual stimuli, which might influence spectral sensitivity. Avian retinal photoreceptors contain light absorbing carotenoid-rich oil droplets that affect vision. Carotenoids are also important plumage components. However, our understanding of the regulation of carotenoids in oil droplets remains rudimentary. Among birds, Melopsittacus undulatus has probably the best-studied colour vision, shows profound intraspecific variation in plumage colour, and increased plasma carotenoids during moult. We used microspectrophotometry to determine whether a relationship exists between oil droplet carotenoid concentration and plumage pigmentation, and tested for sex and spatial variation in droplet absorbance across the retina. Absorbance of one variety of P-type droplets was higher in males. No relationship was found between droplet absorbance and plumage colour. We found a spatial pattern of droplets absorbance across the retina that matched a pattern found in another parrot, and other avian species. Our work provides insights into the development and maintenance of retinal oil droplets and suggests a common mechanism and function for carotenoid deposition in the retina across bird species. PMID- 21979103 TI - Calcium-induced calcium release from the sarcoplasmic reticulum can be evaluated with a half-logistic function model in aequorin-injected cardiac muscles. AB - PURPOSE: Release of calcium (Ca(2+)) from the sarcoplasmic reticulum (SR) induced by Ca(2+) influx through voltage-dependent sarcolemmal L-type Ca(2+) channels (CICR) in cardiac muscle cells has been implicated as a potential target contributing to anesthetic-induced myocardial depression. In an earlier study, we found that (1) a half-logistic (h-L) function, which represents a half-curve of a sigmoid logistic function with a boundary at the inflection point, curve-fits the first half of the ascending phases of the isometric myocardial tension and isovolumic left ventricular (LV) pressure waveforms better than a mono exponential (m-E) function and (2) the h-L time constants are useful as inotropic indices. We report here our investigation of the potential application of an h-L function to the analysis of the first half of the ascending phase of the Ca(2+) transient curve (faCaT) that precedes and initiates myocardial contraction and the increase in LV pressure. METHODS: Ca(2+) transients (CaT) were measured using the Ca(2+)-sensitive photoprotein aequorin, which was microinjected into seven isolated rabbit right ventricular and 15 isolated mouse LV papillary muscles. The faCaT data from the beginning of twitch stimulation to the maximum of the first order time derivative of Ca(2+) concentration (dCa/dt(max)) was curve-fitted by the least-squares method using h-L and m-E function equations. RESULTS: The mean correlation coefficient (r) values of the h-L and m-E curve-fits for the faCaTs were 0.9740 and 0.9654 (P < 0.05) in the rabbit and 0.9895 and 0.9812 (P < 0.0001) in the mouse. CONCLUSION: The h-L curves tracked the amplitudes and time courses of the faCaTs in cardiac muscles more accurately than m-E functions. Based on this result, we suggest that the h-L time constant may be a more reliable index than the m-E time constant for evaluating the rate of CICR from the SR in myocardial Ca(2+) handling. The h-L approach may provide a more useful model for the study of CICR during the contraction process induced by anesthetic agents. PMID- 21979105 TI - Plagiarism and duplication / two situations, which are difficult to differentiate from each other: plagiarism and duplication. PMID- 21979104 TI - Effects of sevoflurane and propofol on pulmonary inflammatory responses during lung resection. AB - PURPOSE: Pulmonary inflammatory reactions are affected by one-lung ventilation (OLV) and anesthetic agents. However, the effects of anesthetic agents on pulmonary inflammatory reactions may vary. Our previous investigations suggested that inflammatory reactions were more pronounced in the dependent lung during lung resection under general anesthesia with propofol and remifentanil. Therefore, in the present study we attempted to determine the difference in pulmonary inflammatory reaction using either sevoflurane or propofol in both dependent and nondependent lungs during OLV. METHODS: Forty adult patients undergoing elective lung resection were randomized to receive either propofol (n = 20) or sevoflurane (n = 20) as the main anesthetic agent. Intraoperative analgesia was provided by remifentanil in both groups. Epithelial lining fluid (ELF) was obtained from each lung using a bronchoscopic microsampling method. ELF and plasma levels of inflammatory cytokines were measured using multiplexed bead based immunoassays before and after OLV. RESULTS: Epithelial lining fluid levels of interleukin (IL)-1beta, IL-6, and IL-8 were significantly increased in the dependent lung and the nondependent lung after OLV compared with baseline levels (P < 0.05). Moreover, IL-6 ELF level in the dependent lung was significantly higher in the propofol group than in the sevoflurane group after OLV (P < 0.001). CONCLUSION: One-lung ventilation induced inflammatory responses of the bronchial epithelia in the dependent lung and the nondependent lung during lung resection. Moreover, this inflammatory response was significantly suppressed by sevoflurane compared with propofol. Furthermore, the antiinflammatory effect of sevoflurane was more pronounced in the dependent lung than in the nondependent lung during OLV. PMID- 21979106 TI - [We built the first public radial angiography laboratory contrary to the hesitation that conventional coronary angiography could have been performed in Erzincan]. PMID- 21979107 TI - [Events that have not been addressed in the previous issue]. PMID- 21979108 TI - Brief report: approaches to 31P-MRS in awake, non-sedated children with and without autism spectrum disorder. AB - We piloted a suite of approaches aimed to facilitate a successful series of up to four brain and muscle (31)Phosphorus-Magnetic Resonance Spectroscopy ((31)P-MRS) scans performed in one session in 12 awake, non-sedated subjects (ages 6-18), 6 with autism spectrum disorders (ASD) and 6 controls. We targeted advanced preparation, parental input, physical comfort, short scan protocols, allocation of extra time, and subject emotional support. 100% of subjects completed at least one brain scan and one leg muscle scan: 42 of 46 attempted scans were completed (91%), with failures dominated by exercise muscle scans (completed in 6/6 controls but 3/6 cases). One completed scan lacked usable data unrelated to subject/scan procedure (orthodonture affected a frontal brain scan). As a group, these methods provide a foundation for conduct and enhancement of future MR studies in pediatric subjects with ASD. PMID- 21979109 TI - Brief report: Platelet-poor plasma serotonin in autism. AB - Possible explanations for the well-replicated platelet hyperserotonemia of autism include an alteration in the platelet's handling of serotonin (5 hydroxyserotonin, 5-HT) or an increased exposure of the platelet to 5-HT. Measurement of platelet-poor plasma (PPP) levels of 5-HT appears to provide the best available index of in vivo exposure of the platelet to 5-HT. Mean (+/- SD) concentrations of PPP 5-HT observed in the autism (N = 18), hyperserotonemic subgroup (N = 5) and control (N = 24) groups were 0.86 +/- 0.53, 0.87 +/- 0.43 and 0.86 +/- 0.36 nM, respectively. The results suggest that the hyperserotonemia of autism is not due to increased exposure of the platelet to 5-HT and make it more likely that the factor(s) contributing to the hyperserotonemia of autism have to do with the platelet's handling of 5-HT. PMID- 21979111 TI - Prospective evaluation of the nipple-areola complex sparing mastectomy for risk reduction and for early-stage breast cancer. AB - BACKGROUND: Psychological effects of mastectomy for women with breast cancer have driven treatments that optimize cosmesis while strictly adhering to oncologic principles. Although skin-sparing mastectomy is oncologically safe, questions remain regarding the use of nipple-areola complex (NAC)-sparing mastectomy (NSM). We prospectively evaluated NSM for patients undergoing mastectomy for early-stage breast cancer or risk reduction. METHODS: We enrolled 33 early-stage breast cancer and high-risk patient; 54 NSMs were performed. NAC viability and surgical complications were evaluated. Intraoperative and postoperative pathologic assessments of the NAC base tissue were performed. NAC sensory, cosmetic and quality of life (QOL) outcomes were also assessed. RESULTS: Twenty-one bilateral and 12 unilateral NSMs were performed in 33 patients, 37 (68.5%) for prophylaxis and 17 (31.5%) for malignancy. Mean age was 45.4 years. Complications occurred in 16 NACs (29.6%) and 6 skin flaps (11.1%). Operative intervention for necrosis resulted in 4 NAC removals (7.4%). Two (11.8%) of the 17 breasts with cancer had ductal carcinoma-in-situ at the NAC margin, necessitating removal at mastectomy. All evaluable patients had nipple erection at 6 and 12 months postoperatively. Cosmetic outcome, evaluated by two plastic surgeons, was acceptable in 73.0% of breasts and 55.8% of NACs, but lateral displacement occurred in most cases. QOL assessment indicated patient satisfaction. CONCLUSIONS: NSM is technically feasible in select patients, with a low risk for NAC removal resulting from necrosis or intraoperative detection of cancer, and preserves sensation and QOL. Thorough pathologic assessment of the NAC base is critical to ensure disease eradication. PMID- 21979110 TI - Tumor-associated antigen expressing Listeria monocytogenes induces effective primary and memory T-cell responses against hepatic colorectal cancer metastases. AB - PURPOSE: Despite advances in therapy for the treatment of metastatic colorectal cancer, many patients die of hepatic disease. Current immunotherapeutic strategies are likely limited by inhibitory signals from the tumor. To successfully eliminate tumor deposits within an organ, an appropriate immunologic milieu to amplify antitumor responses must be developed. METHODS: We used a murine model utilizing the CT26 colon cancer cell line to analyze primary and memory tumor-specific T-cell responses induced by an attenuated actin A and internalin B deleted immunodominant tumor-associated antigen expressing strain of Listeria monocytogenes for the treatment of metastatic colorectal cancer. RESULTS: Treatment of mice bearing established hepatic metastases with this L. monocytogenes strain led to the generation of a strong initial tumor-specific cytotoxic CD8(+) T-cell response that successfully treated 90% of animals. Tumor antigen-specific central and effector memory T cells were also generated and protected against tumor rechallenge. These cell populations, when measured before and after tumor rechallenge, showed a marked expansion of antigen-specific effector CD8(+) effector memory T cells. This strain of L. monocytogenes was able to down-modulate the expression of the immune checkpoint molecule, PD-1, within the tumor microenvironment but had variable effects on CTLA-4 expression. CONCLUSIONS: This L. monocytogenes strain generated a highly effective antitumor T-cell response, providing a basis for the development of this vaccine platform in patients with liver metastases. PMID- 21979112 TI - A high body mass index in esophageal cancer patients does not influence postoperative outcome or long-term survival. AB - BACKGROUND: The body mass index (BMI) in the general population has increased over the past decades. A high BMI is a known risk factor for the development of esophageal adenocarcinoma. Several studies on the influence of a high BMI on the postoperative course and survival after esophagectomy have shown contradictory results. The aim of the present study was to determine the influence of a high BMI on postoperative complications and survival among a large cohort of esophageal cancer patients. METHODS: Patients who underwent an esophagectomy between 1993 and 2010 were divided into three groups according to their BMI: normal weight (<25 kg/m(2)), overweight (25-30 kg/m(2)) or obese (>= 30 kg/m(2)). Severity of complications was scored according to the Dindo classification, which was divided into three categories: no complications, minor to moderate complications, and severe complications. Long-term survival was determined according to the Kaplan-Meier method. RESULTS: A total of 736 esophagectomy patients were divided into three groups: normal weight (n = 352), overweight (n = 308), and obese (n = 72). Complications rates were similar for all groups (65 72%, P = 0.241). The incidence of anastomotic leakage was higher among obese patients compared to the other groups (20% vs. 10-12% respectively, P = 0.019), but there was no significant difference between the three groups regarding the severity of complications according to the Dindo classification (P = 0.660) or in 5-year survival rates (P = 0.517). CONCLUSIONS: A high BMI is not associated with an increased incidence or severity of complications after esophagectomy; however, anastomotic leakage occurred more frequently in obese patients. Five-year survival rates were not influenced by the preoperative BMI. A high BMI is therefore ought not be an exclusion criterion for esophagectomy. PMID- 21979113 TI - Precise pathologic examination decreases the false-negative rate of sentinel lymph node biopsy in gastric cancer. AB - BACKGROUND: Gastric cancer has been identified as a target for sentinel lymph node (SLN) navigational surgery. Although accurate evaluation of SLNs is essential for applying the SLN concept to gastric cancer surgery, there is no standardized pathologic examination protocol for SLNs in gastric cancer. METHODS: A total of 231 SLNs from 69 patients with cT1-2, N0 gastric cancer were prospectively examined in this study. During the operation, SLNs were sliced at 2 mm intervals, and frozen sections were analyzed by hematoxylin and eosin (HE) staining in 35 patients or HE staining with rapid immunohistochemistry (IHC) for pancytokeratin (CK) in 34 patients. HE staining and CK IHC were performed postoperatively on each remaining SLN. Non-SLNs were evaluated with 2 levels of HE slides and 1 CK IHC. RESULTS: Of 35 patients, metastasis was identified in 10 patients by intraoperative HE staining, and in 12 patients by postoperative HE staining and CK IHC. Two patients had isolated tumor cells (ITCs) detectable by postoperative CK IHC; these patients had non-SLN metastasis. We enrolled another 34 patients and examined 147 SLNs by frozen HE and rapid IHC. In this cohort, 26 patients with negative SLNs by intraoperative examination did not have non-SLN metastasis even after deeper sectioning and CK IHC of non-SLNs (sensitivity, 100%; false negative value, 0%). CONCLUSIONS: Our study indicated that precise and detailed intraoperative examination decreases the false-negative rate of SLN biopsy. ITCs in SLNs should not be overlooked, and rapid IHC can be helpful for detecting ITCs intraoperatively. PMID- 21979114 TI - Acupuncture as an adjunct to pulmonary rehabilitation. AB - PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation and by both systemic and airway inflammation. In COPD, acupuncture has been shown to improve quality-of-life scores and decrease breathlessness; similar findings have also been reported after pulmonary rehabilitation (PR). The hypothesis of this study was that acupuncture in conjunction with pulmonary rehabilitation would improve COPD outcome measures compared to pulmonary rehabilitation alone. METHODS: The design was a randomized prospective study; all subjects had COPD. There were 19 controls, 25 who underwent PR, and 16 who had both acupuncture and PR. The primary outcome measure was a change in measures of systemic inflammation at the end of PR and at 3 month followup. Lung function, including maximum inspiratory pressure (PiMax), quality-of-life scores, functional capacity including steps taken, dyspnea scores, and exercise capacity, were secondary endpoints. RESULTS: After PR, both groups had significantly improved quality-of-life scores, reduced dyspnea scores, improved exercise capacity, and PiMax, but no change in measures of systemic inflammation compared with the controls. There were no differences in most of the outcome measures between the 2 treatment groups except that subjects who had both acupuncture and PR remained less breathless for a longer period. CONCLUSION: The addition of acupuncture to PR did not add significant benefit in most of the outcomes measured. PMID- 21979115 TI - From a glial syncytium to a more restricted and specific glial networking. AB - In the brain, glia represents the cell population that expresses the highest level of connexins, the membrane protein constituents of gap junction channels and hemichannels. This statement has initially led to propose the existence of a glial syncytium. Since then, functional studies have established that connexin channel-mediated communication between glial cells was more restricted and plastic that primarily thought. In particular, this is the case for astrocytes that form functional networks of communicating cells. Altogether these findings lead to reconsider the interaction between neurons and glia that should not be solely studied at the single cell level but also at a more integrated level as the interplay between neuronal circuits and glial networks. PMID- 21979116 TI - Genomic structure, polymorphism and expression of the horse alpha-actinin-3 gene. AB - Gene characterization is an important feature for genome annotation and more particularly for candidate genes that could be selected in domestic species. Associations between an alpha-actinin-3 gene polymorphism and muscle performance were reported in humans involving a nonsense mutation (R577X) and in mice after inactivation of the gene. Here, we characterized the equine alpha-actinin-3 (ACTN3) gene by sequencing and transcript analysis. The cDNA was determined to be 3.47 kb in length with an open reading frame of 2709 bp expectedly encoding a protein 902 amino acids long. The ACTN3 gene is 13.2 kb long and contains 21 exons. The equine ACTN3 gene has a ubiquitous expression but it is overexpressed in skeletal muscles with fast fibers of type IIb. No alternative transcripts were observed. Sequencing the cDNA revealed 8 SNPs, 6 in the coding and 2 in the 3' non-coding regions with no amino acid change and not affecting potential miRNA targets. The equine in silico promoter sequence reveals a structure with two regions similar to those of other mammalian species. PMID- 21979117 TI - Biology of aortic aneurysms and dissections. AB - The biology of aortic aneurysm and dissection has evolved to where we now understand the genetic implications of changes in extracellular matrix proteins, smooth muscle cells, and growth factors and how they affect aortic wall homeostasis. These predeterminants are influenced by smoking, hypertension, and atherosclerosis, and the result in an inflammatory response coupled to an accelerated proteolytic cascade that disrupts both elastin and collagen in the aortic wall. PMID- 21979118 TI - Acute Aortic Treatment Center. AB - Acute aortic syndromes are a life-threatening set of conditions that require rapid triage and intervention to obtain satisfactory outcomes. The Methodist Hospital is the first institution to establish an Acute Aortic Treatment Center (AATC) based on a clinical care pathway that expedites the care of acute aortic syndromes. This pathway has resulted in a 64% reduction in time to definitive therapy and a reduction in intensive care unit (ICU) length of stay. Establishment of a multidisciplinary pathway to treat acute aortic syndromes improves efficiency and enhances outcomes. PMID- 21979119 TI - The current status of endovascular repair of abdominal aortic aneurysms (EVAR). AB - Abdominal aortic aneurysms (AAA) affect close to a quarter of a million people in the United States every year. Intervention is designed to treat the AAA when the patient becomes symptomatic and to prevent the fatality associated with rupture. Physicians and patients should weigh the risks associated with intervention compared to the risk of rupture for the particular size of the aneurysm and the patient's comorbidities. Thus, the decision to intervene, especially in asymptomatic aneurysms, is mostly based on clinical judgment. Endovascular AAA repair (EVAR) is attractive in that it offers a minimally invasive approach that obviates a major abdominal procedure and cross-clamping of aorta. We report on the current affairs of the major clinical trails evaluating the outcomes of patients undergoing EVAR and describe the current devices available in the United States for endovascular repair. PMID- 21979120 TI - The current status of endovascular repair of thoracic aortic aneurysms (TEVAR). AB - Thoracic endovascular aortic repair (TEVAR) has been one of the most important advances in the management of thoracic aortic disease in the past two decades. The procedure was originally developed by Dake and colleagues in 1994 for the treatment of descending thoracic aortic aneurysm (DTAA), using the same principles as EVAR for the treatment of abdominal aortic aneurysm (AAA). The first device approved for this indication was the TAG device (W.L. Gore & Associated, Inc., Flagstaff, AZ) in 2005. Since then there has been a plethora of changes and new developments related to thoracic endovascular aortic repair. This article will summarize the major updates related to TEVAR, focusing on three main aspects: what is new in device technology and future prospects; the expanding indications of TEVAR for the treatment of other pathologies and the newly developed techniques involved; and a glimpse at the expected future direction in the field. PMID- 21979121 TI - Endovascular repair of ruptured abdominal and thoracic aortic aneurysms. AB - Management of acute pathology remains one of the most challenging clinical entities, with a persistently high mortality rate both prior to and upon arrival to a hospital. Responding to the distinct advantages of endovascular approaches to aortic disease, many high-volume cardiovascular centers have focused on endovascular therapies for managing patients with ruptured or leaking aortic aneurysms and other acute aortic syndromes. Nonetheless, similar to outcomes for other surgical emergencies, time and efficiency are critical in managing these conditions. Early diagnosis, transport to an appropriate acute care facility, rapid institution of optimal medical management, availability of cardiovascular anesthesia and intensive care, and appropriate and timely surgical intervention continue to be the keys to success. This article discusses the endovascular approach to ruptured abdominal and thoracic aortic aneurysms. PMID- 21979122 TI - Changing paradigm in endovascular treatment of descending thoracic aortic dissections. AB - Descending thoracic dissections originating distal to the origin of the left subclavian artery carry a significant mortality if left untreated. Past thinking advocated avoiding surgical treatment of acute Stanford type B or DeBakey type III dissections, reserving therapy for chronic dissections over 14 days to a month after presentation. The current evolution of endovascular devices for the treatment of thoracic aneurysms has proven helpful in treating this pathology in a less invasive manner when compared to open surgical repair. The paradigm for treatment has evolved beyond the nature of the timing of the dissection: the current trend for treatment considers clinical findings and the development of complications. Complicated dissections include those that have developed aneurysmal dilatation >5.5 or 6 cm, organ or distal limb malperfusion, aortic rupture, uncontrolled hypertension even after adequate medical therapy, and persistent pain including rapid expansion of the affected aorta, among others (Table 1). This article reports on the current paradigm involving thoracic endovascular aortic repair (TEVAR) of Stanford type B or DeBakey type III dissections. PMID- 21979123 TI - Advanced aortic imaging: future directions. AB - There have been dramatic advances in aortic imaging over the last decade. Some of these capabilities have been driven by the development of aortic endografts, the need for accurate measurement of aortic dimensions, and capabilities for simulating endograft placement. The development of three-dimensional (3D) reconstruction has rapidly moved from being an additional luxury item to a commodity, either packaged into advanced imaging systems or freely available as downloadable, highly advanced software such as OsiriX for the Macintosh computer. Other advances such as dynamic magnetic resonance angiography (MRA) have resulted from continuous improvement in the hardware (acquisition of signal) and software (post-processing capabilities) of these imaging systems. We are particularly intrigued by the ability of these capabilties to improve the diagnosis and treatment of aortic disease. Furthermore, there is a rapidly emerging field of creating a 3D image in the interventional suite, which can potentially be used to steer catheter-based robots in a manner never before conceived. These various components will be described below. PMID- 21979124 TI - Robotic aortic surgery. AB - Surgical robotics was first utilized to facilitate neurosurgical biopsies in 1985, and it has since found application in orthopedics, urology, gynecology, and cardiothoracic, general, and vascular surgery. Surgical assistance systems provide intelligent, versatile tools that augment the physician's ability to treat patients by eliminating hand tremor and enabling dexterous operation inside the patient's body. Surgical robotics systems have enabled surgeons to treat otherwise untreatable conditions while also reducing morbidity and error rates, shortening operative times, reducing radiation exposure, and improving overall workflow. These capabilities have begun to be realized in two important realms of aortic vascular surgery, namely, flexible robotics for exclusion of complex aortic aneurysms using branched endografts, and robot-assisted laparoscopic aortic surgery for occlusive and aneurysmal disease. PMID- 21979125 TI - Fenestrated and branched endografts. AB - Thoracoabdominal aneurysm repair is undergoing a paradigm shift. The evolution of branched and fenestrated grafts has expanded the use of endografts to the visceral aorta and the arch of the aorta and broadened the spectrum of patients who can now be considered suitable for endografting. In turn, these advances have lead to a decrease in mortality and morbidity at specialized centers and are propelling the development of a series of modular devices to facilitate wider dispersion of the technology. Preoperative case planning, advanced imaging, and technical experience are keys to successful outcomes. This review examines the current state of fenestrated and branched endografting and the workarounds that have been developed to increase the use of endovascular aortic repair (EVAR). PMID- 21979126 TI - When to replace the ascending aorta? AB - Ascending aortic aneurysm, while usually detected incidentally, is a serious condition that requires close monitoring and timely surgical follow up. Management of patients with thoracic aortic aneurysms (TAA) is optimally performed in a multidisciplinary manner that prevents or delays the need for surgical intervention. Patients with aneurysmal degeneration should be followed in a medical aortic clinic that manages all risk factors in an effort to delay or prevent the need for replacement of the ascending aorta. Symptoms, aortic size, growth rate, and genetic/familial factors are taken into account to develop a treatment plan specific to each patient that is in line with the most recent national guidelines. This article provides an evidence-based overview and key recommendations for intervention on the ascending aorta. PMID- 21979127 TI - Aortic arch debranching: advanced and hybrid techniques. AB - Aortic arch procedures have traditionally involved complex surgery with increased risk of mortality and morbidity. Throughout the last decade, however, novel and safe surgical approaches aimed at debranching the great vessels with definitive aortic arch repair have been developed. Currently, hybrid arch procedures allow for open or minimally invasive aortic access to be complemented by endovascular stent-graft techniques, which may eliminate the need for prolonged hypothermic circulatory arrest and its associated complications. Hybrid thoracic aortic and arch repairs have become the preferred approach, with open procedures performed only if hybrid approaches are not possible for technical reasons. In the future, aortic pathology may also benefit from the development of branched and fenestrated endografts that would be deployed in a modular fashion. This article describes the rationale, procedural steps, and recent outcomes data of novel aortic arch procedures. PMID- 21979128 TI - Advanced in aortic root surgery. AB - The aortic root is often affected by aneurysmal degeneration of the ascending aorta or dissection. It is important for the clinician to be familiar with current guidelines and recommendations for detection, monitoring, and intervention of the aneurysmal aortic root. Timely surgical referral to an experienced aortic center allows for close monitoring and possible intervention that may preserve the aortic valve in appropriate cases and avoid disastrous complications such as aortic dissection, rupture, or death. Patients with bicuspid aortic valve syndrome or connective tissue disorders (e.g. Marfan syndrome) are particularly at risk and should be followed aggressively. Whenever possible, attempts should be made to preserve or repair the aortic valve using valve-sparing aortic root replacement techniques. This article provides an overview of recent advances in management of the aortic root, including guidelines for surgical intervention, technical procedures, and outcomes. PMID- 21979129 TI - Mandatory HPV vaccination and political debate. PMID- 21979130 TI - Hypoxia inducible factor-1alpha gene polymorphisms in Korean patients with pre eclampsia. AB - BACKGROUND: Placental hypoxia has been implicated in the pathogenesis of pre eclampsia. Hypoxia inducible factor-1alpha (HIF-1alpha) is activated by low oxygen tension and is a key regulator of genes involved in the cellular responses to hypoxia. AIM: We determined whether maternal blood c.1722C>T (Pro582Ser) and c.1790G>A (Ala588Thr) polymorphisms in exon 12 of the HIF-1alpha gene are associated with pre-eclampsia. SUBJECTS AND METHODS: Subjects included 163 pre eclamptic patients (48 mild and 115 severe preeclampsia) and 194 healthy pregnant women. Polymorphisms were genotyped by PCR and direct DNA sequencing. RESULTS: There were no significant differences in genotype or allele frequencies of the c.1772C>T and c.1790G>A polymorphisms of the HIF-1alpha gene among the study groups. Moreover, subgroup analysis according to pre-eclampsia severity revealed no significant differences in genotype or allele frequencies of the HIF-1alpha c.1772C>T and c.1790G>A polymorphism in mild pre-eclamptic compared to severe pre eclamptic group. In addition, there were no significant differences in the frequencies of 3 haplotypes (C-G,-G, T-G, and C-A) between the control and pre eclamptic groups. CONCLUSIONS: Our results suggest that the HIF-1alpha gene polymorphisms are not associated with the development of pre-eclampsia in the studied Korean women population. PMID- 21979132 TI - Lymphangiogenesis is induced during development of periodontal disease. AB - Lymphangiogenesis, the formation of new lymphatics, is associated with chronic inflammation and tissue injury, and its role is to enhance lymphatic flow, immune cell transport, and antigen clearance. It is unknown if lymphangiogenesis takes place during periodontal disease development, and we hypothesized that growth of lymphatic vessels occurs in gingiva during development of periodontitis in mice. Inflammation was induced in gingiva with Porphyromonas gingivalis gavage, and bone resorption was verified after 42 days. Growth of lymphatic and blood vessels was measured after immunofluorescent staining with LYVE-1 and CD31. Expression of vascular endothelial growth factors and 2 inflammatory cytokines was investigated 10 days post-infection. Gingival lymphangiogenesis was found 10 days and 42 days post-infection, but proliferation of vessels was observed only in the shortest observation period. Epithelial expression of vascular growth factors (VEGF) A, C, and D was observed in gingiva, and increased numbers of immune cells expressing VEGF-C were found after infection, along with up-regulation of IL-1beta and TNF alpha at protein levels. We conclude that lymphangiogenesis takes place in gingiva during periodontal disease development, and that up-regulation of vascular growth factor C in recruited immune cells is likely important for the growth of lymphatic vessels. PMID- 21979131 TI - The problem of accelerated atherosclerosis in systemic lupus erythematosus: insights into a complex co-morbidity. AB - Rheumatic autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus (SLE), are associated with antibodies to "self" antigens. Persons with autoimmune diseases, most notably SLE, are at increased risk for developing accelerated cardiovascular disease. The link between immune and inflammatory responses in the pathogenesis of cardiovascular disease has been firmly established; yet, despite our increasing knowledge, accelerated atherosclerosis continues to be a significant co-morbidity and cause of mortality in SLE. Recent animal models have been generated in order to identify mechanism(s) behind SLE accelerated atherosclerosis. In addition, clinical studies have been designed to examine potential treatments options. This review will highlight data from recent studies of immunity in SLE and atherosclerosis and discuss the potential implications of these investigations. PMID- 21979133 TI - Glycosphingolipids regulate ameloblastin expression in dental epithelial cells. AB - Neurotrophin 4 (NT-4) and its receptors regulate the differentiation of ameloblasts in tooth development. Gangliosides, sialic acids that contain glycosphingolipids (GSLs), are involved in a variety of membrane-associated cell physiological functions such as ligand-receptor signal transmission. However, the expression patterns and functions of GSLs during tooth development remain unclear. In this study, we identified strong expressions of GM3 and LacCer in dental epithelium, which give rise to differentiation into enamel-secreting ameloblasts. Exogenous GM3 and LacCer in dental epithelial cells induced the expression of ameloblastin (Ambn), while it was also interesting that GM3 synergistically exerted enhancement of NT-4-mediated Ambn expression. In addition, consistently exogenous GM3 and LacCer in dental epithelial cells induced distinct activation of extracellular signal-regulated kinase 1/2 (ERK1/2), an event upstream of the expression of Ambn. Furthermore, depletion of GSLs from dental epithelial cells by D-threo-1-phenyl-2-decanoylamino-3 morpholino-1-propanol (D-PDMP) inhibited Ambn expression as well as phosphorylation of ERK1/2. In contrast, exogenous addition of GM3 or LacCer rescued the phosphorylation of ERK1/2 repressed by pre-treatment with D-PDMP. Taken together, these results suggest that GM3 and LacCer are essential for NT-4 mediated Ambn expression, and contribute to dental epithelial cell differentiation into ameloblasts. PMID- 21979134 TI - Formation and photocatalytic decomposition of a pellicle on anatase surfaces. AB - The acquired dental pellicle plays a critical role in the adhesion and detachment of dental plaque bacteria. It has been reported that titanium dioxide biomaterials decompose single-protein films by photocatalysis. However, it is not known whether this can also be achieved with complex structured pellicle films. This in vitro study investigated in real-time the formation and photocatalytic decomposition of human pellicle at anatase-saliva interfaces. Nanostructured polycrystalline anatase layers were deposited on titanium-coated quartz crystals by magnetron-sputtering, serving as a model for titanium implant surfaces. The quartz crystals were used as acoustic sensors in a quartz-crystal microbalance (QCM) system with dissipation. In situ UV irradiation of pellicle-covered anatase caused a statistically significant decrease of the adsorbed salivary mass. In contrast, photocatalytic decomposition of pellicle could not be observed on reference titanium surfaces. Wettability characterization revealed superhydrophilicity of anatase upon UV irradiation, whereas titanium was unaffected. XPS measurements provide further information concerning the decomposition of the salivary films. The results suggest that the photocatalytic activity of polycrystalline anatase-modified biomaterial surfaces is able to decompose complex structured macromolecular pellicle films. Therefore, this study opens the way to surface modifications supporting therapeutic approaches of biofilm removal. PMID- 21979135 TI - Video EEG outcome on children referred following a single unprovoked afebrile seizure. PMID- 21979136 TI - Directed evolution combined with rational design increases activity of GpdQ toward a non-physiological substrate and alters the oligomeric structure of the enzyme. AB - Directed evolution was used to enhance the activity of the glycerophosphodiesterase enzyme from Enterobacter aerogenes, GpdQ, toward bis(para-nitrophenol) phosphate (BpNPP), a substrate that is frequently used to assay phosphodiesterases. Native GpdQ has a low level of activity toward BpNPP while the evolved enzymes exhibited k(cat) values that were well over 100 times better while improvements in k(cat)/K(m) of around 500 times were observed along with improved activity we observed a change in the oligomeric structure in the evolved enzymes. The native enzyme is a hexamer with tightly associated dimers related by a 3-fold axis. The stability of the dimer was attributed in part to the cap domain that forms a disulfide bond with its 2-fold-related subunit and in part due to the fact that dimerization results in burying 23.6% of the monomer's accessible surface area. The cap domain also forms the top of the active site and contributes an essential part of the interface between 3-fold-related molecules. The evolved proteins quickly lost one of the cysteine residues that formed the disulfide bond and other mutations that might stabilize the cap domain. The likely effect of these mutations was to open up the active site for the new substrate and to favor the formation of dimeric molecules. The breakdown of the oligomeric structure was accompanied by a reduction in the thermal stability of the protein-as monitored by the residual activity of the native and mutant proteins following pre-incubation at elevated temperatures. A discussion on the evolutionary implications of these studies is presented. PMID- 21979137 TI - Chronic effects of Pinus radiata and Eucalyptus globulus kraft mill effluents and phytosterols on Daphnia magna. AB - Two kraft pulp mill effluents were compared in terms of their chronic toxicity to Daphnia magna. One resulted from pulping Pinus radiata and the other came from a parallel processing of Pinus radiata and Eucalyptus globulus (mixed kraft pulp mill effluent). The concentration of phytosterols found in the mixed kraft pulp mill effluent was higher than in the effluent from Pinus radiata, with values of 0.1082 and 0.02 MUg/L, respectively. The phytosterols per se are responsible for 12.9% and 8.1% of the deviation from the natural shape, while the kraft pulp mill effluents account for 25.6%-27.8% of shape deviation. The role of beta-sitosterol and stigmasterol is discussed in relation to endocrine disruption. PMID- 21979138 TI - Biochemical effect of carbaryl on oxidative stress, antioxidant enzymes and osmolytes of cyanobacterium Calothrix brevissima. AB - Carbaryl is used in Indian agriculture for control of rice field pests and it is next to Benzene hexachloride in pesticide consumption. In present study, carbaryl (0, 10, 20, 30 and 40 mg/L) induced toxic effects were observed after 21 days exposure on a non target rice field biofertilizer Calothrix brevissima with special reference to oxidative stress, antioxidant enzymes and osmolytes. At 40 mg/L carbaryl the decrease in carotenoid, chlorophyll, phycobilin and protein were 63%, 43%, 40% and 40% respectively in comparison to control. Total carbohydrate, malondialdehyde, superoxide dismutase, ascorbate peroxidase, catalase and osmolytes showed enhancement at all the treated concentration. Increased amount of MDA (46% at 40 mg/L) indicated free radical mediated deleterious effect of carbaryl. Enhancement of SOD, APX, CAT and osmolytes in presence of carbaryl indicated their involvement in free radical scavenging. SOD, CAT and APX showed maximum activities (79%, 64% and 39% respectively) at 40 mg/L carbaryl. The order of enhancement in osmolytes was glycine-betaine (66%) > proline (54%) > sucrose (50%) at 40 mg/L which might be another adaptive defense strategy of the cyanobacterium against the pesticide. PMID- 21979139 TI - Metal concentrations of river water and sediments in West Java, Indonesia. AB - To determine the water environment and pollutants in West Java, the contents of metals and general water quality of the Ciliwung River in the Jakarta area were measured. High Escherichia coli number (116-149/mL) was detected downstream in the Ciliwung River. In addition to evaluate mercury pollution caused by gold mining, mercury contents of water and sediment samples from the Cikaniki River, and from paddy samples were determined. The water was not badly polluted. However, toxic metals such as mercury were detected at levels close to the baseline environmental standard of Indonesia (0.83-1.07 MUg/g of sediments in the Cikaniki River). From analyses of the paddy samples (0.08 MUg/g), it is considered that there is a health risk caused by mercury. PMID- 21979140 TI - Organochlorine pesticide residues in eggs and tissues of house sparrow, Passer domesticus, from Tamil Nadu, India. AB - This study provides information on the current status of contamination by organochlorine pesticides (OCPs) in eggs and tissues of House Sparrow, Passer domesticus, in Tamil Nadu, India. The mean concentration of total hexachlorocyclohexane (?HCH) and total dichloro-diphenyl-trichloroethane (?DDT) in eggs ranged from 0.01 to 1.81 MUg/g and 0.02 to 1.29 MUg/g, respectively. Concentration of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) ranged from below detectable limit (BDL) to 0.64 MUg/g, representing more than 60% of the ?DDTs. About 28% of samples had p,p'-DDE levels above the critical concentration associated with reproductive impairment. However, the mean concentrations of cyclodiene insecticides were less than 0.5 MUg/g. Although OCPs levels detected in tissues are not indicative of toxicity, continuous monitoring is recommended. PMID- 21979141 TI - Persistent organic pollutants in muscle and feather of ten avian species from Mazandaran Province of Iran, on the coast of the Caspian Sea. AB - Feather and muscle of 10 avian species (n = 46), were analyzed for polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs). Muscle contained significantly higher PCB and OCP than liver and feather. Mean muscle and feather PCB was 408.5 +/- 134.5 and 32 +/- 4.5 ng/g wet weight. Highly chlorinated PCBs were found in muscle and liver while feather had PCBs with less chlorination. Gulls had highest levels of both pollutants. Gull feather PCB and OCP were strongly correlated with their levels in the liver and muscle tissues (0.6 < r < 0.9, p < 0.01). Analysis of gull feather can be used as a non-invasive method for monitoring organic pollutants. PMID- 21979142 TI - Interferon regulator factor 1/retinoic inducible gene I (IRF1/RIG-I) axis mediates 25-hydroxycholesterol-induced interleukin-8 production in atherosclerosis. AB - AIMS: In this study, the role of retinoic inducible gene I (RIG-I)-mediated signalling in the inflammation of atherosclerosis was investigated to explain the pathology of atherosclerosis. METHODS AND RESULTS: Human and mouse primary cells were exposed to 25-hydroxycholesterol followed by examination of gene expression and activation of the signal pathway with biochemical and molecular biological techniques. A mouse atherosclerotic model was also used. We found that RIG-I was induced in macrophages and endothelium by 25-hydroxycholesterol. Interferon regulatory factor 1 is a key transcription factor for the induction of RIG-I by 25-hydroxycholesterol. The induction of interleukin-8 and growth-regulated protein alpha, the mouse interleukin-8 homologue, by 25-hydroxycholesterol is mediated by RIG-I signalling. RIG-I transduces the signal to downstream molecules, mitochondrial antiviral-signalling protein, transforming growth factor beta-activated kinase 1, and mitogen-activated protein kinase, leading to the activation of nuclear factor kappaB, activator protein-1, and nuclear factor interleukin-6, all of which are required for the expression of interleukin-8. Finally, we observed that RIG-I is highly expressed in atherosclerotic lesions. CONCLUSION: Our data demonstrate that RIG-I signalling mediates atherosclerotic inflammation. Targeting RIG-I signalling should provide a way to inhibit atherosclerotic inflammation, which holds potential for the therapy of atherosclerosis. PMID- 21979143 TI - Is air pollution of the 20th century a cause of current asthma hospitalisations? PMID- 21979144 TI - Pulmonary and cutaneous nodules in an immunocompromised patient. PMID- 21979146 TI - Smoking and smoking cessation in relation to all-cause mortality and cardiovascular events in 25,464 healthy male Japanese workers. AB - BACKGROUND: Smoking is still a major health problem among males in Japan. The effects of smoking and quitting on mortality and cardiovascular disease (CVD) need updating. METHODS AND RESULTS: This was a prospective cohort study with a median follow-up of 7.5 years of a total of 25,464 healthy male Japanese workers aged 20-61 years who were not on any medication. The adjusted hazard ratios (HR; 95% confidence interval) for all-cause death were 1.51 (0.73, 2.94), 1.68 (1.07, 2.70), 1.30 (0.70, 2.34), and those for total CVD events 1.91 (0.72, 4.67), 2.94 (1.65, 5.63), and 3.25 (1.69, 6.54) for light smokers (1-10 cigarettes/day), moderate smokers (11-20/day), and heavy smokers (>= 21/day) compared to never smokers, respectively. Total CVD events increased dose-dependently as the number of cigarettes/day increased. Acute myocardial infarction was increased at any level of smoking. Stroke was increased at a moderate level of smoking. Quitting for >= 4 years, compared with continuing smokers, reduced the HR for all-cause death to 0.64 (0.38, 1.01), and total CVD events to 0.34 (0.17, 0.62). CONCLUSIONS: In healthy young- and middle-aged Japanese males, a significant increase in HR for total CVD events was confirmed for a smoking level of 11-20 cigarettes/day. Quitting reduced the HR for total CVD events, with quitting for >= 4 years being statistically significant. A similar trend was observed for all cause mortality. PMID- 21979147 TI - Value of real-time transesophageal 3-dimensional echocardiography in guiding ablation of isthmus-dependent atrial flutter and pulmonary vein isolation. AB - In the past decade, both the range of indications and the efficacy and safety of interventional electrophysiology has improved considerably. This progress is attributed to both the accumulating experience of electrophysiologists and the advances in technological tools facilitating the diagnosis and treatment of cardiac arrhythmias. Real-time 3-dimensional transesophageal echocardiography (RT 3D TEE) has emerged as a new imaging tool in the clinical arena. Its ability to image in "real time" cardiac structures "en face" and the almost entire length of intracardiac catheters has made this technique a promising imaging tool to guide percutaneous catheter-based procedures. More recently it has been used in monitoring ablation procedures. In this review, the advantages and current limitations of RT 3D TEE during ablation of cavotricuspid isthmus-dependent atrial flutter and pulmonary vein isolation are described. PMID- 21979145 TI - Craniocervical arterial dissection in children: diagnosis and treatment. AB - OPINION STATEMENT: Diagnosis of craniocervical arterial dissection (CCAD) in children begins with a careful history and physical in a child with a transient ischemic attack (TIA) or arterial ischemic stroke (AIS). The extent of radiologic evaluation for suspected CCAD is based upon careful consideration of the risks associated with the best imaging techniques, weighed against the benefits of enhanced vascular imaging with better diagnostic sensitivity. Although conventional angiography (CA) and CT angiography (CTA) have a higher sensitivity than magnetic resonance angiography (MRA), they are accompanied by risks: for CA, femoral hematoma, femoral arterial pseudoaneurysm, recurrent AIS, and radiation exposure; for CTA, radiation. For children (non-neonates) with suspected CCAD, MRI with MRA is recommended as the first-line imaging study. MRI usually includes diffusion-weighted, FLAIR, and T1 images of the brain, and T1 or T2 fat saturation axial imaging through the neck. MRA should include 3D time-of-flight MRA of the head and neck (from the aortic arch through the circle of Willis). Contrast-enhanced MRA should be highly considered in neck imaging. If MRI/MRA is equivocal, CCAD is strongly suspected but not detected on MRI/MRA (especially in the posterior circulation), or the child has recurrent events, additional imaging of the craniocervical vasculature is likely warranted. Individual clinical circumstances warrant careful, case-by-case consideration. Treatment of CCAD in children is challenging and differs for intracranial and extracranial dissections. In extracranial CCAD, we most commonly use anticoagulation for 6 weeks to 6 months in patients with TIA or AIS. Typically, unfractionated heparin is used in the acutely ill patient at heightened risk for bleeding (because of its short half-life), whereas low-molecular-weight heparin (LMWH) or warfarin are reserved for the stable patient. If the history is suspicious for dissection (head and neck trauma, recent cervical chiropractic manipulation, recent car accident, or neck pain), we consider treatment for dissection even with normal MRI/MRA. For patients with CCAD with a stroke size greater than one third to one half of the middle cerebral artery territory (or other bleeding risk factors) and extracranial CCAD, in whom there is concern about heightened risk for hemorrhagic conversion, we commonly use aspirin therapy during the acute phase. Regardless of their treatment in the initial weeks to months, we subsequently treat all patients with aspirin for 1 year after their event, and sometimes longer if they have other risk factors. Interventional techniques, such as extracranial cerebral arterial stent placement or selective occlusion, are understudied in children. Interventional techniques are typically reserved for patients who fail aggressive medical management and have recurrent TIA or AIS. The diagnosis and treatment of intracranial dissection is extraordinarily challenging in children, in whom inflammatory intracranial arteriopathies are common. When intracranial arteriopathy is clearly associated with dissection, the clinician should look for the presence of subarachnoid hemorrhage and/or dissecting aneurysm. Treatment decisions should be made by a multidisciplinary pediatric stroke team, given the lack of data in this area. Intracranial cerebral artery stent placement carries high risk and is not recommended for intracranial CCAD in children. Most importantly, we educate all children with CCAD and their parents about the paucity of evidence in the treatment of this disease, the risks of enhanced imaging techniques such as CTA or CA, and the challenges involved in weighing the risks of aggressive therapies and interventions against the costs of unclear diagnosis and potentially ineffective treatments. We also educate our patients with CCAD about the signs and symptoms of recurrence and the importance of emergent evaluation. PMID- 21979148 TI - Review of the cost-effectiveness of interventions to improve seamless care focusing on medication. AB - AIM OF THE REVIEW: This review of the international literature aims to assess the evidence and its methodological quality relating to the cost-effectiveness of interventions to improve seamless care focusing on medication. METHOD: Studies were identified by searching Medline, EMBASE, Centre for Reviews and Dissemination databases, Cochrane Database of Systematic Reviews, and EconLit up to March 2011 using search terms related to health economics and to seamless care. To be included, economic evaluations had to explore the costs and consequences of an intervention to improve seamless care focusing on medication as compared with usual care. Methodological quality of studies was assessed by considering perspective; design; source of clinical and economic data; cost and consequence measures; allowance for uncertainty; and incremental analysis. Costs were actualized to 2007 values. RESULTS: Eight studies on medication interventions for hospitalized patients in the transition between ambulatory and hospital care were included in the review. A variety of types of medication interventions and target populations have been assessed, but the evidence is limited to one economic evaluation for each particular intervention type and each specific target population. Most studies demonstrated an impact of interventions on compliance and (re)hospitalization rates and costs. The studies did not find an impact on quality of life or symptoms. Economic evaluations suffered from methodological limitations related to the narrow perspective; restriction to health care costs only; exclusion of costs of the intervention; use of intermediate consequence measures; no allowance for uncertainty; and absence of incremental analysis. CONCLUSION: In light of the small number of economic evaluations and their methodological limitations, it is not possible to recommend a specific intervention to improve seamless care focusing on medication on health economic grounds. PMID- 21979149 TI - Implicit processes in pathological skin picking: responses to skin irregularities predict symptom severity and treatment susceptibility. AB - BACKGROUND AND OBJECTIVES: Implicit cognitive processes are relevant in understanding the development and maintenance of psychopathology and dysfunctional behaviours. The present study investigated the role of implicit processes in pathological skin picking (PSP). METHODS: Using an Approach Avoidance Task (AAT), we examined automatic response tendencies towards skin picking-related photographs in a sample of 34 college students who suffered from PSP and participated in a randomized, waiting-list controlled treatment study. RESULTS: In comparison to a control sample (n = 49), PSP patients displayed significantly decelerated reaction times (distraction) in response to photographs of skin irregularities and a tendency to respond with avoidance to photographs of skin irregularities. Both distraction and avoidance in reaction to photographs of skin irregularities were significantly associated with current skin picking severity. Moreover, the strength of distraction in response to skin irregularities predicted unique variance in skin picking severity at post measurement, over and above the effect of skin picking severity at pre measurement and the effect of treatment condition. For the treatment condition, higher initial distraction predicted better treatment outcome (lower skin picking severity at post-measurement), whereas it predicted symptom deterioration at post treatment for untreated participants. LIMITATIONS: The specific characteristics of PSP patients (mainly female university students) and the relatively small sample size may compromise generalizability of findings. CONCLUSIONS: In PSP, affective distraction in response to skin irregularities seems to characterize an important process related to symptom severity as well as treatment susceptibility. PMID- 21979150 TI - Fatty acid transport proteins, implications in physiology and disease. AB - Uptake of long-chain fatty acids plays pivotal roles in metabolic homeostasis and human physiology. Uptake rates must be controlled in an organ-specific fashion to balance storage with metabolic needs during transitions between fasted and fed states. Many obesity-associated diseases, such as insulin resistance in skeletal muscle, cardiac lipotoxicity, and hepatic steatosis, are thought to be driven by the overflow of fatty acids from adipose stores and the subsequent ectopic accumulation of lipids resulting in apoptosis, ER stress, and inactivation of the insulin receptor signaling cascade. Thus, it is of critical importance to understand the components that regulate the flux of fatty acid between the different organ systems. Cellular uptake of fatty acids by key metabolic organs, including the intestine, adipose tissue, muscle, heart, and liver, has been shown to be protein mediated and various unique combinations of fatty acid transport proteins (FATPs/SLC27A1-6) are expressed by all of these tissues. Here we review our current understanding of how FATPs can contribute to normal physiology and how FATP mutations as well as hypo- and hypermorphic changes contribute to disorders ranging from cardiac lipotoxicity to hepatosteatosis and ichthyosis. Ultimately, our increasing knowledge of FATP biology has the potential to lead to the development of new diagnostic tools and treatment options for some of the most pervasive chronic human disorders. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease. PMID- 21979151 TI - Phosphatidylcholine biosynthesis and lipoprotein metabolism. AB - Phosphatidylcholine (PC) is the major phospholipid component of all plasma lipoprotein classes. PC is the only phospholipid which is currently known to be required for lipoprotein assembly and secretion. Impaired hepatic PC biosynthesis significantly reduces the levels of circulating very low density lipoproteins (VLDLs) and high density lipoproteins (HDLs). The reduction in plasma VLDLs is due in part to impaired hepatic secretion of VLDLs. Less PC within the hepatic secretory pathway results in nascent VLDL particles with reduced levels of PC. These particles are recognized as being defective and are degraded within the secretory system by an incompletely defined process that occurs in a post endoplasmic reticulum compartment, consistent with degradation directed by the low-density lipoprotein receptor and/or autophagy. Moreover, VLDL particles are taken up more readily from the circulation when the PC content of the VLDLs is reduced, likely due to a preference of cell surface receptors and/or enzymes for lipoproteins that contain less PC. Impaired PC biosynthesis also reduces plasma HDLs by inhibiting hepatic HDL formation and by increasing HDL uptake from the circulation. These effects are mediated by elevated expression of ATP-binding cassette transporter A1 and hepatic scavenger receptor class B type 1, respectively. Hepatic PC availability has recently been linked to the progression of liver and heart disease. These findings demonstrate that hepatic PC biosynthesis can regulate the amount of circulating lipoproteins and suggest that hepatic PC biosynthesis may represent an important pharmaceutical target. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease. PMID- 21979152 TI - On deflection fields, weak-focusing and strong-focusing storage rings for polar molecules. AB - In this paper, we analyze electric deflection fields for polar molecules in terms of a multipole expansion and derive a simple but rather insightful expression for the force on the molecules. Ideally, a deflection field exerts a strong, constant force in one direction, while the force in the other directions is zero. We show how, by a proper choice of the expansion coefficients, this ideal can be best approximated. We present a design for a practical electrode geometry based on this analysis. By bending such a deflection field into a circle, a simple storage ring can be created; the direct analog of a weak-focusing cyclotron for charged particles. We show that for realistic parameters a weak-focusing ring is only stable for molecules with a very low velocity. A strong-focusing (alternating gradient) storage ring can be created by arranging many straight deflection fields in a circle and by alternating the sign of the hexapole term between adjacent deflection fields. The acceptance of this ring is numerically calculated for realistic parameters. Such a storage ring might prove useful in experiments looking for an EDM of elementary particles. PMID- 21979153 TI - Well-aligned ZnO nanowires with excellent field emission and photocatalytic properties. AB - Well-aligned ZnO nanowires (NWs) were successfully synthesized on Si(100) by the process of carbothermal reduction and vapor-liquid-solid method. Scanning electron microscopy and transmission electron microscopy results confirmed that ZnO NWs were single crystalline wurtzite structures and grew along the [0001] direction. The influences of substrate temperature and total pressure on the growth were discussed. The well-aligned ZnO NWs show good field emission properties, and the emitter constructed of pencil-like ZnO NWs exhibited a low turn-on field (3.82 V MUm(-1)) and a high field enhancement factor (beta = 2303). Finally, we demonstrated that the as-prepared ZnO NWs with small diameter on the substrate have good photocatalytic activity toward degradation of methylene blue. Using ZnO NWs with Au nanoparticles (NPs) would decrease the recombination rate of hole-electron pairs due to the great shift of the Fermi level to the conduction band. Hence, adding Au NPs was a promising method to enhance the photocatalytic performance of ZnO NWs. It is significant that photocatalyst fabricated by ZnO NWs can apply to the degradation of organic pollution, and solve the environmental issues. PMID- 21979154 TI - Copy-number variation: the balance between gene dosage and expression in Drosophila melanogaster. AB - Copy-number variants (CNVs) reshape gene structure, modulate gene expression, and contribute to significant phenotypic variation. Previous studies have revealed CNV patterns in natural populations of Drosophila melanogaster and suggested that selection and mutational bias shape genomic patterns of CNV. Although previous CNV studies focused on heterogeneous strains, here, we established a number of second-chromosome substitution lines to uncover CNV characteristics when homozygous. The percentage of genes harboring CNVs is higher than found in previous studies. More CNVs are detected in homozygous than heterozygous substitution strains, suggesting the comparative genomic hybridization arrays underestimate CNV owing to heterozygous masking. We incorporated previous gene expression data collected from some of the same substitution lines to investigate relationships between CNV gene dosage and expression. Most genes present in CNVs show no evidence of increased or diminished transcription, and the fraction of such dosage-insensitive CNVs is greater in heterozygotes. More than 70% of the dosage-sensitive CNVs are recessive with undetectable effects on transcription in heterozygotes. A deficiency of singletons in recessive dosage-sensitive CNVs supports the hypothesis that most CNVs are subject to negative selection. On the other hand, relaxed purifying selection might account for the higher number of protein-protein interactions in dosage-insensitive CNVs than in dosage-sensitive CNVs. Dosage-sensitive CNVs that are upregulated and downregulated coincide with copy-number increases and decreases. Our results help clarify the relation between CNV dosage and gene expression in the D. melanogaster genome. PMID- 21979155 TI - In memoriam: Jacques Monod (1910-1976). PMID- 21979156 TI - Near-neutrality, robustness, and epigenetics. AB - The nearly neutral theory emphasizes the interaction of drift and weak selection in evolution. With progress of genome biology, the applicability of the nearly neutral theory has expanded. The genome-wide analyses of synonymous and nonsynonymous substitutions at protein-coding regions show prevalence of very weak selection. Many patterns of evolution of gene regulation are also in agreement with the nearly neutral prediction. Our consideration on near neutrality expands in relation to the progress on molecular understanding of robustness and epigenetics. Both are bridges to link genotypes with phenotypes and important for understanding how weak selection and drift interact in the evolution of complex systems. PMID- 21979157 TI - Evolution under environmental stress at macro- and microscales. AB - Environmental stress has played a major role in the evolution of living organisms (Hoffman AA, Parsons PA. 1991. Evolutionary genetics and environmental stress. Oxford: Oxford University Press; Parsons PA. 2005. Environments and evolution: interactions between stress, resource inadequacy, and energetic efficiency. Biol Rev Camb Philos Soc. 80:589-610). This is reflected by the massive and background extinctions in evolutionary time (Nevo E. 1995a. Evolution and extinction. Encyclopedia of Environmental Biology. New York: Academic Press, Inc. 1:717-745). The interaction between organism and environment is central in evolution. Extinction ensues when organisms fail to change and adapt to the constantly altering abiotic and biotic stressful environmental changes as documented in the fossil record. Extreme environmental stress causes extinction but also leads to evolutionary change and the origination of new species adapted to new environments. I will discuss a few of these global, regional, and local stresses based primarily on my own research programs. These examples will include the 1) global regional and local experiment of subterranean mammals; 2) regional experiment of fungal life in the Dead Sea; 3) evolution of wild cereals; 4) "Evolution Canyon"; 5) human brain evolution, and 6) global warming. PMID- 21979158 TI - Chance and necessity in eye evolution. AB - Charles Darwin has proposed the theory that evolution of live organisms is based on random variation and natural selection. Jacques Monod in his classic book Chance and Necessity, published 40 years ago, presented his thesis "that the biosphere does not contain a predictable class of objects or events, but constitutes a particular occurrence, compatible indeed with the first principles, but not deducible from those principals and therefore, essentially unpredictable." Recent discoveries in eye evolution are in agreement with both of these theses. They confirm Darwin's assumption of a simple eye prototype and lend strong support for the notion of a monophyletic origin of the various eye types. Considering the complexity of the underlying gene regulatory networks the unpredictability is obvious. The evolution of the Hox gene cluster and the specification of the body plan starting from an evolutionary prototype segment is discussed. In the course of evolution, a series of similar prototypic segments gradually undergoes cephalization anteriorly and caudalization posteriorly through diversification of the Hox genes. PMID- 21979159 TI - Isochores and the regulation of gene expression in the human genome. AB - It is well established that changes in the phenotype depend much more on changes in gene expression than on changes in protein-coding genes, and that cis regulatory sequences and chromatin structure are two major factors influencing gene expression. Here, we investigated these factors at the genome-wide level by focusing on the trinucleotide patterns in the 0.1- to 25-kb regions flanking the human genes that are present in the GC-poorest L1 and GC-richest H3 isochore families, the other families exhibiting intermediate patterns. We could show 1) that the trinucleotide patterns of the 25-kb gene-flanking regions are representative of the very different patterns already reported for the whole isochores from the L1 and H3 families and, expectedly, identical in upstream and downstream locations; 2) that the patterns of the 0.1- to 0.5-kb regions in the L1 and H3 isochores are remarkably more divergent and more specific when compared with those of the 25-kb regions, as well as different in the upstream and downstream locations; and 3) that these patterns fade into the 25-kb patterns around 5kb in both upstream and downstream locations. The 25-kb findings indicate differences in nucleosome positioning and density in different isochore families, those of the 0.1- to 0.5-kb sequences indicate differences in the transcription factors that bind upstream and downstream of genes. These results indicate differences in the regulation of genes located in different isochore families, a point of functional and evolutionary relevance. PMID- 21979160 TI - Molecular Darwinism: the contingency of spontaneous genetic variation. AB - The availability of spontaneously occurring genetic variants is an important driving force of biological evolution. Largely thanks to experimental investigations by microbial geneticists, we know today that several different molecular mechanisms contribute to the overall genetic variations. These mechanisms can be assigned to three natural strategies to generate genetic variants: 1) local sequence changes, 2) intragenomic reshuffling of DNA segments, and 3) acquisition of a segment of foreign DNA. In these processes, specific gene products are involved in cooperation with different nongenetic elements. Some genetic variations occur fully at random along the DNA filaments, others rather with a statistical reproducibility, although at many possible sites. We have to be aware that evolution in natural ecosystems is of higher complexity than under most laboratory conditions, not at least in view of symbiotic associations and the occurrence of horizontal gene transfer. The encountered contingency of genetic variation can possibly best ensure a long-term persistence of life under steadily changing living conditions. PMID- 21979162 TI - Timely assessment of infarct volume and brain atrophy in acute hemispheric infarction for early surgical decompression: strict cutoff criteria with high specificity. AB - PURPOSE: For a large hemispheric infarction, the clinical decision for decompressive surgery is commonly made on the basis of both radiological data showing brain swelling with herniation and concomitant neurological deterioration. However, for early decompressive surgery before clinical deterioration, strict cutoff criteria with a high specificity are required on the basis of timely assessment of the infarct volume. MATERIALS AND METHODS: Sixty one patients who presented with a hemispheric infarction were initially evaluated using diffusion-weighted images (DWIs) within 14 h and computed tomography (CT) scans 24 +/- 4 h after stroke onset to assess the infarct volume and midline shift. In addition, brain atrophy was evaluated using the bicaudate ratio. Twenty one patients developed a malignant course, while 40 patients experienced a non malignant course. RESULTS: According to a receiver-operating characteristic curve analysis for 50 patients with a bicaudate ratio <0.16, an initial infarct volume >160 ml in the DWI achieved a 97% specificity and 76% sensitivity, while an initial infarct volume >135 ml achieved an 86% specificity and 91% sensitivity. For the follow-up CT scans, an infarcted lesion volume >220 ml and midline shift >3.7 mm provided a 100% and 98% specificity, respectively. CONCLUSIONS: For the patients who presented with an acute hemispheric infarction and had a bicaudate ratio <0.16, an initial infarct volume >160 ml in a DWI within 14 h after stroke onset is highly predictive of a malignant course. In addition, an infarct volume >220 ml or midline shift >3.7 mm in the follow-up CT approximately 24 h after stroke onset facilitates early surgical decompression before clinical deterioration. PMID- 21979163 TI - Use of a strip-clip technique to maintain transposition of a vertebral artery in microvascular decompression surgery. PMID- 21979164 TI - The effect of transient proanthocyanidins preconditioning on the cross-linking and mechanical properties of demineralized dentin. AB - Proanthocyanidin-based preconditioners were prepared by adding powdered proanthocyanidins-rich grape seed extract to various solvents at different concentrations. Demineralized dentin specimens were preconditioned for 20, 30, 60 or 120 s, followed by the evaluation of their cross-linking degree, mechanical properties and micromorphology. The cross-linking degree of the demineralized dentin collagen exhibited concentration- and time- dependent increase after preconditioning treatment, irrespective of the preconditioner and the solvent. When treated for the same exposure time, specimens after 15% proanthocyanidins preconditioning resulted in the highest mean ultimate tensile strength compared with all the other groups tested. Five percent glutaraldehyde control group produced the highest cross-linking degree, but the ultimate tensile strength was lower than that of 15% proanthocyanidins group. The field emission scanning electron microscopy confirmed that the demineralized dentin collagen was in a homogeneous and regular arrangement after preconditioning and maintained expanding, regardless of the surface moisture conditions. PMID- 21979165 TI - The influence of Sr and H3PO4 concentration on the hydration of SrCaHA bone cement. AB - Sr-contained calcium hydroxyapatite (SrCaHA) cement is a potential biomaterial for in vivo bone repair and surgery fixation due to its excellent biodegradability, bioactivity, biocompatibility, easily shaping and self hardening. We had ever reported the in vitro physiochemical properties, biocompatibility and in vivo degradability of the SrCaHA cement obtained by mixing a cement powder of Ca(4)(PO(4))(2)O/CaHPO(4)/SrHPO(4) and a cement liquid of diluted H(3)PO(4) aqueous solution. In the present study, we intensively studied the influences of both Sr content and H(3)PO(4) concentration in diluted phosphoric acid aqueous solution on the setting time, hydration heat-liberation behaviours, and real-time microstructure and phase evolutions of the SrCaHA cement. The results show that both PO(4)(3-) and H(+) ions in PA solution attended the hydration reaction as reactants, and thus the increase of the PA concentration not only promoted the dissolution of Ca(4)(PO(4))(2)O but also pushed the hydration progress of SrCaHA bone cement. Sr content exhibits a remarkable retardation role on the apatite transformation of the SrCaHA cement pastes which probably attributed to its higher degree of supersaturation for yielding apatite crystals and lower transformation rate when exposed to the Sr(2+)-containing hydration system. This present results contribute to a better understanding on the hydration mechanism of the new SrCaHA cement and help to the more precisely controlling of its hydration process. PMID- 21979166 TI - Conjugation of gold nanoparticles to polypropylene mesh for enhanced biocompatibility. AB - Polypropylene mesh materials have been utilized in hernia surgery for over 40 years. However, they are prone to degradation due to the body's aggressive foreign body reaction, which may cause pain or complications, forcing mesh removal from the patient. To mitigate these complications, gold nanomaterials were attached to polypropylene mesh in order to improve cellular response. Pristine samples of polypropylene mesh were exposed to hydrogen peroxide/cobalt chloride solutions to induce formation of surface carboxyl functional groups. Gold nanoparticles were covalently linked to the mesh. Scanning electron microscopy confirmed the presence of gold nanoparticles. Differential scanning calorimetry and mechanical testing confirmed that the polypropylene did not undergo any significantly detrimental changes in physicochemical properties. A WST-1 cell culture study showed an increase in cellularity on the gold nanoparticle-polypropylene mesh as compared to pristine mesh. This study showed that biocompatibility of polypropylene mesh may be improved via the conjugation of gold nanoparticles. PMID- 21979167 TI - Autofluorescence imaging and the quantitative intensity of fluorescence for evaluating the dysplastic grade of colonic neoplasms. AB - BACKGROUND AND AIMS: Autofluorescence imaging (AFI) is a novel technology which can capture fluorescence emitted from intestinal tissues. While AFI is useful for detecting colorectal neoplasms, it is unclear whether AFI can facilitate the diagnosis by differentiating the extent of dysplasia of colorectal neoplasms. This study investigated the efficacy of AFI in discriminating high-grade from low grade adenoma. MATERIALS AND METHODS: Sixty-seven patients who underwent colonoscopy with AFI were enrolled in this study. The AFI images obtained from 158 lesions in these patients were visually classified into four categories, namely, green (G), green with magenta spots (GM), magenta with green spots (MG), and magenta (M), according to their color intensities, immediately after the examination. The AFI images of the lesions were quantified using an image analytical software program (F index). Either the F index or the visual assessment was prospectively compared with the dysplastic grade. RESULTS: The F index of the high-grade adenomas was significantly lower than that of the low grade adenomas, hyperplasia, and normal mucosa (p < 0.05). The incidence of the lesions classified into the M classification for high-grade adenomas (55.6%) was significantly higher than that of either low-grade adenomas (20.8%) or hyperplasia (0%). No correlation was observed between the F index or the visual classification and the tumor shape. The F index was not influenced by the size of the lesion, while the size was significantly associated with the visual classification of AFI. CONCLUSIONS: AFI, particularly the F index, is considered to be a useful procedure for estimating the dysplastic grade of colonic adenomas. PMID- 21979168 TI - Macrophages as cell-based delivery systems for nanoshells in photothermal therapy. AB - Site-specific delivery of nanoparticles poses a significant challenge, especially in the brain where the blood-brain barrier prevents the entry of most therapeutic compounds including nanoparticle-based anti-cancer agents. In this context, the use of macrophages as vectors for the delivery of gold-silica nanoshells to infiltrating gliomas will be reviewed in this article. Gold-silica nanoshells are readily phagocytosed by macrophages without any apparent toxic effects, and the results of in vitro studies have demonstrated the migratory potential of nanoshell-loaded macrophages in human glioma spheroids. Of particular interest is the observation that, after near-infrared exposure of spheroids containing nanoshell-loaded macrophages, sufficient heat was generated to suppress spheroid growth. Collectively, these findings demonstrate the potential of macrophages as nanoshell delivery vectors for photothermal therapy of gliomas, and they certainly provide the basis for future animal studies. PMID- 21979169 TI - Relationship between strain levels and permeability of the plasma membrane in statically stretched myoblasts. AB - Deep tissue injury (DTI) is a life-threatening type of pressure ulcer which initiates subdermally with muscle necrosis at weight-bearing anatomical locations, where localized elevated tissue strains exist. Though it has been suggested that excessive sustained soft tissue strains might compromise cell viability, which then initiates the DTI, there is no experimental evidence to describe how specifically such a process might take place. Here, we experimentally test the hypothesis that macroscopic tissue deformations translated to cell-level deformations and in particular, to localized tensile strains in the plasma membrane (PM) of cells, increase the permeability of the PM which could disrupt vital transport processes. In order to determine whether PM permeability changes can occur due to static stretching of cells we measured the uptake of fluorescein isothiocyanate (FITC)-labeled Dextran (molecular weight = 4 kDa) by deformed vs. undeformed myoblasts, using a fluorescence-activated cell sorting (FACS) method. These PM permeability changes were then correlated with tensile strains in the PM which correspond to the levels of substrate tensile strain (STS) that were applied in the experiments. The PM strains were evaluated by means of confocal-microscopy-based cell-specific finite element (FE) modeling. The FACS studies demonstrated a statistically significant rise in the uptake of the FITC-labeled Dextran with increasing STS levels in the STS <= 12% domain, which thereby indicates a rise in the permeability of the PM of the myoblasts with the extent of the applied cellular deformation. The cell-specific FE modeling simulating the experiments further demonstrated that applying average PM tensile strains which exceed 3%, or, applying peak PM tensile strains over 9%, substantially increases the permeability of the PM of myoblasts to the Dextran. Moreover, the permeability of the PM grew rapidly with any further increase in PM strains, though there were no significant changes in the uptake above average and peak PM tensile strain values of 9 and 26%, respectively. These results provide an experimental basis for studying the theory that cell-level deformation diffusion relationships may be involved in determining the tolerance of soft tissues to sustained mechanical loading, as relevant to the etiology of DTI. PMID- 21979171 TI - beta2 adrenergic-mediated reduction of blood glutamate levels and improved neurological outcome after traumatic brain injury in rats. AB - BACKGROUND: Isoflurane-anesthetized rats subjected to traumatic brain injury (TBI) show a transient reduction in blood L-glutamate levels. Having previously observed that isoproterenol produces a sustained decrease in blood glutamate levels in naive rats, we investigated the possible effects of nonselective and selective beta1 and beta2 adrenergic agonists and antagonists both on blood glutamate levels and on the neurological outcomes of rats subjected to TBI. METHODS: Rats received either 10 mL/kg of isotonic saline 1 hour after TBI, 50 ug/kg of isoproterenol pretreatment 30 minutes before TBI, 10 mg/kg of propranolol pretreatment 60 minutes before TBI, 10 mg/kg of metoprolol pretreatment 60 minutes before TBI, or 10 mg/kg of butaxamine pretreatment 40 minutes before TBI and 10 minutes before pretreatment with 50 ug/kg isoproterenol or 10 mg/kg of propranolol 60 minutes after TBI. A neurological severity score (NSS) was measured at 1, 24, and 48 hours after TBI. Blood glutamate, blood glucose, mean arterial blood pressure, and heart rate were measured at the time of drug injection, at the time of TBI, 60 minutes after TBI, and 90 minutes after TBI. RESULTS: Blood glutamate levels decreased spontaneously by 60 minutes after TBI in the control group (P<0.05), reverting to baseline levels by 90 minutes after TBI. A pretreatment with either 10 mg/kg of metoprolol 60 minutes before TBI or with 50 ug/kg of isoproterenol 30 minutes before TBI also reduced blood glutamate levels (P<0.05) both at 90 minutes after TBI and improved the NSS measured 24 and 48 hours after TBI in comparison with the control saline-treated group. However, a 10-mg/kg butoxamine pretreatment 40 minutes before TBI and 10 minutes before pretreatment with 50 ug/kg of isoproterenol or 10 mg/kg of propranolol 60 minutes before TBI neither affected blood glutamate levels across time after TBI nor caused any significant change in the NSS measured 24 and 48 hours after TBI in comparison with the control saline-treated group. A strong correlation (r(2)=0.73) was demonstrated between the percent decrease in blood glutamate levels at 90 minutes after TBI and the percent improvement of NSS measured 24 hours after TBI. CONCLUSIONS: The results suggest that the transient blood glutamate reduction seen after TBI is the result of a stress response and of the activation of the sympathetic nervous system through the beta2 adrenergic receptors, causing an increase of the brain-to-blood efflux of glutamate observed with excess brain glutamate levels after a brain insult. This strongly correlates with the neurological improvement observed 24 hours after TBI. PMID- 21979170 TI - Neutrophil elastase cleaves the murine hemidesmosomal protein BP180/type XVII collagen and generates degradation products that modulate experimental bullous pemphigoid. AB - Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease associated with autoantibodies against the hemidesmosomal proteins BP180 and BP230. In the IgG passive transfer model of BP, blister formation is triggered by anti-BP180 IgG and depends on complement activation, mast cell degranulation, and neutrophil recruitment. Mice lacking neutrophil elastase (NE) do not develop experimental BP. Here, we demonstrated that NE degrades recombinant mouse BP180 within the immunodominant extracellular domain at amino acid positions 506 and 561, generating peptide p561 and peptide p506. Peptide p561 is chemotactic for neutrophils both in vitro and in vivo. Local injection of NE into B6 mice recruits neutrophils to the skin, and neutrophil infiltration is completely blocked by co-injection with the NE inhibitor alpha1-proteinase inhibitor. More importantly, NE directly cleaves BP180 in mouse and human skin, as well as the native human BP180 trimer molecule. These results demonstrate that (i) NE directly damages the extracellular matrix and (ii) NE degradation of mouse BP180 generates neutrophil chemotactic peptides that amplify disease severity at the early stage of the disease. PMID- 21979172 TI - Direct and indirect impact of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on adult mouse Leydig cells: an in vitro study. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related substances are ubiquitous environmental pollutants that exert adverse effects on reproductive processes. In testis, Leydig cells which produce testosterone are under hormonal and local control exerted by cytokines including TNFalpha. Using mouse Leydig primary cell cultures as a model, we studied the effects of TCDD on the steroidogenic outcome of Leydig cells and the gene expression levels of Ccl5 and Cxcl4, previously shown to be target genes of TCDD in testis. We found that TCDD did not alter the steroidogenic outcome of Leydig cells but that it up-regulated Cxcl4 gene expression levels. TCDD also impacted Ccl5 gene expression when cells had been co treated with TNFalpha. TCDD action probably initiated with binding to the aryl hydrocarbon receptor (AhR) present on Leydig cells. TCDD regulated the gene expression levels of AhR (transient down-regulation) and its repressor AhRR and Cyp1b1 (up-regulation). The trophic human chorionic gonadotropin (hCG) hormone did not impact AhR, its repressor AhRR or Cyp1b1 but it opposed the TCDD-enhanced AhRR mRNA levels. Conversely, TNFalpha stimulated AhR gene expression levels. Collectively, it is suggested that the impact of TCDD on expression of target genes in Leydig cells may operate under the complex network of hormones and cytokines. PMID- 21979173 TI - Toxicokinetic modeling of captan fungicide and its tetrahydrophthalimide biomarker of exposure in humans. AB - Measurement of tetrahydrophthalimide (THPI) in urine has been used for the biomonitoring of exposure to the widely used captan fungicide in workers. To allow a better understanding of the toxicokinetics of captan and its key biomarker of exposure, a human multi-compartment model was built to simulate the transformation of captan into THPI and its subsequent excretion while accounting for other non-monitored metabolites. The mathematical parameters of the model were determined from best-fits to the time courses of THPI in blood and urine of five volunteers administered orally 1mg/kg and dermally 10mg/kg of captan. In the case of oral administration, the mean elimination half-life of THPI from the body (either through faeces, urine or metabolism) was found to be 13.43 h. In the case of dermal application, mean THPI elimination half-life was estimated to be 21.27 h and was governed by the dermal absorption rate. The average final fractions of administered dose recovered in urine as THPI were 3.6% and 0.02%, for oral and dermal administration, respectively. Furthermore, according to the model, after oral exposure, only 8.6% of the THPI formed in the GI reaches the bloodstream. As for the dermal absorption fraction of captan, it was estimated to be 0.09%. Finally, the average blood clearance rate of THPI calculated from the oral and dermal data was 0.18 +/- 0.03 ml/h and 0.24 +/- 0.6 ml/h while the predicted volume of distribution was 3.5 +/- 0.6l and 7.5 +/- 1.9l, respectively. Our mathematical model is in complete accordance with both independent measurements of THPI levels in blood (R(2)=0.996 for oral and R(2)=0.908 for dermal) and urine (R(2)=0.979 for oral and R(2)=0.982 for dermal) as well as previous experimental data published in the literature. PMID- 21979174 TI - Water-soluble germanium nanoparticles cause necrotic cell death and the damage can be attenuated by blocking the transduction of necrotic signaling pathway. AB - Water-soluble germanium nanoparticles (wsGeNPs) with allyamine-conjugated surfaces were fabricated and emit blue fluorescence under ultraviolet light. The wsGeNP was physically and chemically stable at various experimental conditions. Cytotoxicity of the fabricated wsGeNP was examined. MTT assay demonstrated that wsGeNP possessed high toxicity to cells and clonogenic survival assay further indicated that this effect was not resulted from retarding cell growth. Flow cytometric analysis indicated that wsGeNP did not alter the cell cycle profile but the sub-G1 fraction was absent from treated cells. Results from DNA fragmentation and propidium iodide exclusion assays also suggested that apoptotic cell death did not occur in cells treated with wsGeNP. Addition of a necrosis inhibitor, necrostatin-1, attenuated cell damage and indicated that wsGeNP caused necrotic cell death. Cell signaling leads to necrotic death was investigated. Intracellular calcium and reactive oxygen species (ROS) levels were increased upon wsGeNP treatment. These effects can be abrogated by BAPTA-AM and N-acetyl cysteine respectively, resulting in a reduction in cell damage. In addition, wsGeNP caused a decrease in mitochondrial membrane potential (MMP) which could be recovered by cyclosporine A. The cellular signaling events revealed that wsGeNP increase the cellular calcium level which enhances the production of ROS and leads to a reduction of MMP, consequentially results in necrotic cell death. PMID- 21979175 TI - PCDD, PCDF, and PCB exposure in current and former firefighters from Eastern Siberia. AB - The current study examines whether the occupation of firefighting contributes to exposure to polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (PCBs). We compared serum dioxin concentrations and congener profiles of current firefighters (n=13) with those of men who have ceased employment as firefighters (n=17) and with men employed in occupations other than firefighter (n=10). We found that compared to former or non-firefighters, current firefighters have higher levels of dioxins primarily due to the contribution of PCBs and to a lesser extent PCDFs. PCDFs were significantly higher in former firefighters compared to non-firefighters (p<0.05). Comparisons with studies performed by other investigators suggest that local environmental conditions contribute to some of the elevation of PCBs. The congeners 1,2,3,4,6,7,8 heptachlorodibenzodioxin and PCB-114 were significantly higher in current firefighters when compared to former or non-firefighters. Moreover, levels of these congeners were inversely correlated with years since employed as firefighter (Spearman r=-0.610, p=0.009 and Spearman r=-0.53, p=0.03, respectively). The classes of dioxins show an overall decline with years since employed as firefighters, this decline is most evident with PCDDs (Spearman r= 0.46, p=0.06). Together, the combination of evidence supports firefighting as a source of exposure to dioxins. PMID- 21979176 TI - Practice parameters for the management of rectal prolapse. PMID- 21979177 TI - Long-term outcome of colectomy and ileorectal anastomosis for Crohn's colitis. AB - BACKGROUND: Ileorectal anastomosis is an important surgical option for patients with Crohn's colitis with relative rectal sparing. OBJECTIVE: This study aimed to audit outcomes of ileorectal anastomosis for Crohn's and factors associated with proctectomy and reoperation. DESIGN: This retrospective study involved a chart review and contacting patients. SETTINGS: Patients with Crohn's colitis who had an ileorectal anastomosis were identified from the Mount Sinai Hospital Inflammatory Bowel Disease Database. PATIENTS: Demographics, operative and perioperative outcomes, and reoperative data were collected. MAIN OUTCOME MEASURES: Five- and 10-year Kaplan-Meier survival estimates and 95% confidence intervals were calculated for survival from proctectomy and Crohn's-related revisional surgery. Cox proportional hazards models were used to model the hazards of proctectomy and Crohn's-related revision on the clinical characteristics of patients. RESULTS: Eighty-one patients had an ileorectal anastomosis for Crohn's disease from 1982 to 2010. The most common indications for surgery were failed medical management (60/81, 74.1%) and a stricture causing obstruction (14/81, 17.3%). Seventy-seven percent (n = 62) had a 1-stage procedure, whereas 23% (n = 19) had a 2-stage procedure (colectomy followed by ileorectal anastomosis). The overall anastomotic leak rate was 7.4% (n = 6). Fifty-six patients had a functioning ileorectal anastomosis at the time of follow up. At 5 and 10 years, 87% (95% CI: 75.5-93.3) and 72.2% (95% CI: 55.8-83.4) of individuals had a functioning ileorectal anastomosis. Eighteen patients required proctectomy for poor symptom control, whereas 11 patients required a small-bowel resection plus redo-ileorectal anastomosis. The mean time to proctectomy from the original ileorectal anastomosis was 88.3 months (SD = 62.1). Smoking was associated with both proctectomy (HR 3.93 (95% CI: 1.46-10.55)) and reoperative surgery (HR 2.12 (95% CI: 0.96-4.72)). LIMITATIONS: : This study was retrospective. CONCLUSIONS: Ileorectal anastomosis is an appropriate operation for selected patients with Crohn's colitis with sparing of the rectum. However, patients must be counseled that the reoperation rate and/or proctectomy rate is approximately 30%. PMID- 21979178 TI - Single-incision versus multiport laparoscopic right and hand-assisted left colectomy: a case-matched comparison. AB - BACKGROUND: New technology for single-incision laparoscopic colectomy is now commercially available, yet advantages of this approach over multiport laparoscopic colectomy have not been demonstrated. OBJECTIVE: This study aimed to compare the outcomes of patients who underwent single-incision vs multiport laparoscopic colectomies. DESIGN: Consecutive patients who underwent single incision laparoscopic colectomies were case matched to patients who underwent multiport laparoscopic colectomies by age, operation, surgeon, diagnosis, and body mass index. Data from a prospective database and the medical records of patients treated were reviewed. SETTINGS: This study took place at 2 tertiary care hospitals. PATIENTS: Forty-six consecutive patients with a body mass index of 24 underwent single-incision laparoscopic colectomies (24 right, 18 sigmoid, 4 low anterior resection). MAIN OUTCOME MEASURES: Perioperative outcomes and cosmesis and body image scores at 90 days were compared. RESULTS: The largest incision length was significantly shorter for the single-incision group. Two patients with single incisions were converted to hand-assisted laparoscopic surgery and 4 required placement of a 5-mm trocar. A significantly greater portion of the operation was performed by the attending surgeons in the single incision group. For right colectomies, operative times were similar. For left colectomies, operative time (149 +/- 30 vs 126 +/- 21 min) was significantly longer for the single-incision group. Time to flatus and bowel movements were significantly shorter for the single-incision group, but length of stay was similar. Cosmetic score was higher for the single-incision group (P = .03). CONCLUSIONS: Single incision is equivalent to multiport laparoscopic colectomy with regard to safety and efficacy with smaller incision size and higher cosmetic scores. Operative times were equivalent, although a greater portion of the operation was performed by the attending surgeons in the single-incision group. Further prospective studies are warranted to evaluate the advantages of single incision laparoscopic colectomy. PMID- 21979179 TI - Early discharge and hospital readmission after colectomy for cancer. AB - BACKGROUND: Early discharge after colectomy has been shown to be feasible in studies from specialty centers, but we hypothesized that benefits of early discharge might be offset by higher risk of readmission in the surgical community as a whole. Minimizing readmissions is a national health policy priority. OBJECTIVE: This study aimed to determine whether hospitals discharging patients early had increased readmission rates. DESIGN: Patients undergoing colectomy surgery for cancer were studied using national Medicare data (MEDPAR database). Multiple logistic regression was performed to determine whether hospitals with a pattern of early discharge (median length of stay <= 5 d after surgery) had increased readmission rates. Results were adjusted for patient comorbidity, emergency operation, laparoscopic surgery, demographic factors, and complications. A separate analysis at the patient level was conducted to determine risk factors for readmission. SETTINGS: Early discharge rates at US acute care hospitals were investigated. PATIENTS: Patients 65 and older undergoing colectomy surgery for cancer (2003-2008, n = 477,461) were included. MAIN OUTCOME MEASURE: The main outcome measure was 30-day, all hospital readmission rates. RESULTS: Hospitals with a pattern of early discharge (median length of stay <= 5 d) were not found to have a higher risk-adjusted readmission rate than hospitals with the usual median length of stay (16.3% vs 15.7%, P = .077). However, changing the cutoff for "early discharge" to <= 4 days revealed an increased risk for readmission among "very early discharge" hospitals (risk adjusted readmission rate 21.3% vs 15.7%, P < .001). At the patient level, independent risk factors for readmission included older age, male sex, black race, lower socioeconomic status, urgent/emergent surgery, comorbidities, complications, open (vs laparoscopic) surgery, and longer length of stay for the index hospitalization. LIMITATIONS: Limitations of this study included the limitations of the administrative data and elderly population. CONCLUSIONS: Hospitals with a pattern of early discharge (median length of stay <= 5 d after surgery) do not have a higher risk-adjusted readmission rate than other hospitals. These results support the safety of early discharge programs in the Medicare population. PMID- 21979180 TI - The anatomy of failures following the ligation of intersphincteric tract technique for anal fistula: a review of 93 patients over 4 years. AB - BACKGROUND: Although the ligation of intersphincteric tract technique is a promising sphincter-preserving option in managing anal fistulas, failures are still seen. OBJECTIVE: This study aimed to illustrate the patterns of failures and recurrences following the ligation of intersphincteric tract procedure for anal fistulas. DESIGN: This study is a retrospective review. SETTINGS: This study was conducted at the Division of Colorectal Surgery, University Surgical Cluster, National University Health System, Singapore, from April 2006 to September 2010. PATIENTS: Ninety-three patients were evaluated. INTERVENTIONS: All patients underwent the ligation of intersphincteric tract procedure for anal fistulas. MAIN OUTCOME MEASURES: Failure was defined as nonhealing of the surgical wound or fistula. Recurrence was defined as the reappearance of the fistula after initial healing. RESULTS: After a median follow-up of 23 (range, 1-85) weeks, there were 7 failures and 6 recurrences. The median time to healing was 4 (range, 1-12) weeks. The freedom from failure or recurrence at 1 year following the ligation of intersphincteric tract procedure was 78% (95% CI: 66%-90%). All 7 failures had discharge at the intersphincteric wound. Four had an unhealed internal opening, and 3 had isolated failures at the intersphincteric wound. Endoanal ultrasonography revealed a less complicated anatomy that enabled successful treatment with either local application of silver nitrate (n = 3) or fistulotomy (n = 4). All 6 recurrences had a demonstrable tract from the previous internal opening to an external opening with healing of the intersphincteric wound. The median time to recurrence was 22 (range, 15-33) weeks from the ligation of the intersphincteric tract procedure. Fistulotomy, repeat ligation of intersphincteric tract, or anocutaneous advancement flap procedure was successfully performed subsequently. CONCLUSION: In patients with early failures, the medialization of the external opening to the intersphincteric wound simplified subsequent management. All recurrences should be reevaluated and managed accordingly. PMID- 21979181 TI - Sustained improvement in the anal sphincter function following surgical plication of rabbit external anal sphincter muscle. AB - BACKGROUND: We recently found that the anal canal function and external anal sphincter contraction can be enhanced by surgically adjusting the EAS muscle sarcomere length in rabbits. A 20% length plication of the external anal sphincter muscle results in significant increase in the anal canal pressure and EAS muscle stress without affecting its passive tension. The durability of the beneficial effect of external anal sphincter muscle plication on the anal canal function is not known. OBJECTIVE: We studied the long-term effects of optimal length external anal sphincter plication on the anal canal pressure, external anal sphincter sarcomere length, and anal canal histology. DESIGN: Female rabbits (n = 16) were anesthetized and either sham (n = 4) or external anal sphincter plication (n = 12) surgery was performed. MAIN OUTCOME MEASURES: The effect of external anal sphincter plication on the anal canal pressure was determined every 2 weeks for 6 months in 6 animals. Anal canal was harvested for sarcomere length and histological assessment. RESULTS: External anal sphincter plication resulted in 50% to 60% increase in the anal canal pressure, and 80% to 90% increase in external anal sphincter muscle stress (during maximum electrical stimulus). The effect of plication was durable for the entire study period of 24 weeks. Sarcomere length increased from 2.11 +/- 0.08 MUm to 2.59 +/- 0.03 MUm immediately after plication and was 2.35 +/- 0.08 MUm at the end of 6 months. Histology revealed no significant differences in the muscle (30% vs 29%) or connective tissue components (70% vs 71%) of the anal canal between control and chronically plicated animals. CONCLUSIONS: Normal external anal sphincter muscle plication results in long-term enhancement of the anal canal function without any untoward effects on the tissue architecture in the rabbit. External anal sphincter muscle plication could be an important strategy to improve the anal canal function in patients with anal incontinence. PMID- 21979182 TI - Determining levels of fecal incontinence in the community: a New Zealand cross sectional study. AB - BACKGROUND: Fecal incontinence is a socially stigmatized condition, and its prevalence in the community has been problematic to quantify because of difficulty with its definition. OBJECTIVE: This study estimates the community prevalence of fecal incontinence in New Zealand by 3 scales of measurement: patient perceptions of a "problem with bowel control," their symptoms, and their quality of life. DESIGN/MAIN OUTCOME MEASURES: A postal survey of 2000 people, aged >18, randomly selected from the national electoral roll, was performed. This used a validated, reliability-tested, anonymous questionnaire, the Comprehensive Fecal Incontinence Questionnaire, incorporating the identification of a "problem with bowel control," the Fecal Incontinence Severity Index, and the Fecal Incontinence Quality of Life Scale. RESULTS: The response rate was 68.7%. A total of 14.7% (95% CI: 12.6-16.7) of participants "felt they had a problem with bowel control" and 12.4% (95% CI: 10.5-14.5) had fecal incontinence when defined using the Fecal Incontinence Severity Index table as "leakage of liquid or solid stool >= 1/month." In terms of quality of life, 26.8% of the population (95% CI: 24.2 29.4) noted some impairment on the Fecal Incontinence Quality of Life Scale. In total, 155 (13.2%) participants reported at least 2 of the 3 possible diagnostic measures, and this may provide a way to incorporate the 3 measures into a new definition of fecal incontinence. LIMITATIONS: This study incorporated a new "generic" question enquiring about an individual's perception of a bowel control problem and also introduced a "cutoff" value for Fecal Incontinence Quality of Life Scale to attempt to identify those with any impairment "due to accidental bowel leakage." CONCLUSIONS: This study helps to highlight some of the challenges involved with suitably identifying those who have fecal incontinence within the community. The prevalence rate of 13.2% represents a realistic measure of the burden of fecal incontinence in the general population, and further research in this area is recommended. PMID- 21979183 TI - Does intra-abdominal desmoid disease affect patients with an ileal pouch differently than those with an ileorectal anastomosis? AB - BACKGROUND: Nobody has analyzed the sequelae of desmoids according to the type of surgery that precipitated them. OBJECTIVE: This study aims to determine whether the clinical effects of abdominal desmoids would be worse in patients with restorative proctocolectomy than in patients with ileorectal anastomosis. DESIGN: This is a retrospective, database study. PATIENTS: Included were patients with familial adenomatous polyposis who had undergone proctocolectomy with IPAA or colectomy and ileorectal anastomosis, and subsequently developed an intra abdominal desmoid tumor. MAIN OUTCOME MEASURES: The primary outcome measures were the clinical course of the desmoids; morbidity, and the requirement for stoma. RESULTS: There were 86 patients: 49 had restorative proctocolectomy and 37 had ileorectal anastomosis. Patient demographics were similar. Average follow-up was 9.8 years (range, 2.7-23.8) and 16.3 years (range, 2.3 - 42.9). Treatment of the desmoids included surgery (64.4% vs 65.6%), medical therapy (69.4% vs 59.5%), chemotherapy (36.2% vs 30.0%), and radiotherapy (4.5% vs 10.0%), and was the same for each group. The overall complication rate of desmoids was similar, approaching 70%. The risk of individual complications was also similar (bleeding (2.0% vs 0.0%), fistula (10.2% vs 13.5%), bowel obstruction (32.7% vs 48.6%), pain (34.7% vs 21.6%), and death related to desmoid tumors (2.0% vs 10.8%)); 38.8% of the restorative proctocolectomy group and 51.4% the ileorectal group had surgery for desmoid tumor complications (P = .21), and 22.4% and 22.2% of patients ultimately had permanent stomas. LIMITATIONS: This study was limited by the relatively small numbers of patients. CONCLUSION: The morbidity associated with desmoid tumors has not been shown to differ, whether they arise after restorative proctocolectomy or ileorectal anastomosis. PMID- 21979184 TI - Increased risk of colorectal cancer and dysplasia in patients with Crohn's colitis and primary sclerosing cholangitis. AB - BACKGROUND: Almost 10% of all patients with primary sclerosing cholangitis receive a diagnosis of Crohn's disease. Clinical characteristics and the risk of colon cancer or dysplasia in Crohn's disease and primary sclerosing cholangitis are less well examined than in ulcerative colitis. OBJECTIVE: This study aimed to describe the clinical characteristics and risk of colorectal dysplasia and cancer in Crohn's disease in patients with primary sclerosing cholangitis. DESIGN: This is a cohort study of all patients diagnosed with primary sclerosing cholangitis and colorectal Crohn's disease at Karolinska University Hospital, Huddinge, 1978 to 2006. Each patient was matched for age and the onset of Crohn's disease to 2 controls with colorectal Crohn's disease without liver disease. SETTING: This study was conducted at a tertiary referral center. PATIENTS: Twenty-eight patients (61% male) with primary sclerosing cholangitis and Crohn's disease and 46 patients (50% male) with Crohn's disease alone were studied. Clinical and endoscopic data were retrieved from medical records. Colonic biopsies from patients with primary sclerosing cholangitis were re-reviewed. MAIN OUTCOME MEASURES: The primary outcome measured was the proportion of patients developing colorectal cancer. RESULTS: Colorectal cancer or dysplasia developed in 9 patients with primary sclerosing cholangitis and in 3 controls. Patients with primary sclerosing cholangitis were more likely to develop colorectal dysplasia or cancer than controls (OR 6.78; 95% CI (1.65-27.9); P = .016). In patients with primary sclerosing cholangitis compared with controls, perianal fistulas occurred in 3% vs 33% (P = .003), bowel strictures occurred in 7% vs 30% (P = .03), and bowel surgery was performed in 18% vs 46% (P = .01). Histological granulomas were seen in 29% of the patients with primary sclerosing cholangitis compared with 43% in controls (P = not significant). LIMITATIONS: This study was limited by its retrospective nature and the limited cohort. CONCLUSIONS: Primary sclerosing cholangitis is a risk factor for the development of colorectal cancer and dysplasia in Crohn's disease. Obstructing disease and perianal fistulas are rare in primary sclerosing cholangitis and less common than in colonic Crohn's disease without liver disease. PMID- 21979185 TI - Dynamic anal endosonography and MRI defecography in diagnosis of pelvic floor disorders: comparison with conventional defecography. AB - BACKGROUND: Pelvic floor disorders are frequent, especially in women. Surgeons need more information on the accuracy of available diagnostic techniques to make therapeutic decisions. OBJECTIVE: This study aimed to compare the accuracy of dynamic anorectal endosonography and dynamic MRI defecography with conventional defecography as the criterion standard in the diagnosis of pelvic floor disorders. DESIGN: We used a prospective crossover design in which patients underwent each procedure in random order within the same month. SETTING: Investigations were conducted at a regional referral center in Marseille, France. PATIENTS: Women with dyschezia who were undergoing diagnostic evaluation were eligible. INTERVENTION: Dynamic anorectal endosonography, dynamic MRI, and conventional defecography were performed in all patients by 3 blinded operators. MAIN OUTCOME MEASURE: The accuracy of dynamic anorectal endosonography and dynamic MRI in the diagnosis of pelvic floor disorders was assessed by calculating sensitivity, specificity, positive and negative predictive values, correlation coefficients, concordance rates, and the Cohen kappa statistic, with conventional defecography used as the criterion standard. RESULTS: The study comprised 56 women with a mean age of 50.7 (SD, 12.5) years. No significant differences were observed between dynamic anorectal endosonography and dynamic MRI in the number of patients with rectocele (P = .49), perineal descent (P = .11 when dynamic anorectal endosonography measured descent of the puborectalis muscle; P = .27 for bladder descent), or enterocele (P = .78); no differences were found between these techniques in sensitivity, specificity, or positive and negative predictive values. Diagnostic concordance with conventional defecography as the standard did not differ significantly between dynamic MRI and dynamic anorectal endosonography: Concordance rates for dynamic anorectal endosonography were 75% for rectocele, 64% for perineal descent, and 91% for enterocele (no rectal intussusception was found with dynamic anorectal endosonography); concordance rates for dynamic MRI were 82% for rectocele, 57% for perineal descent, 93% for enterocele, and 55% for rectal intussusception. Significantly more internal anal sphincter defects were found with dynamic anorectal endosonography than with dynamic MRI defecography: 21 patients (37.5%) vs 12 patients (21.4%); P = .02. Patient tolerance was significantly better for dynamic anorectal endosonography than for dynamic MRI (P = .002) or conventional defecography (P = .005). Most patients said they would choose dynamic anorectal endosonography (72.1%) rather than dynamic MRI (25.6%) or conventional defecography (2.3%) if follow-up were necessary (P < .001). CONCLUSION: Dynamic anorectal endosonography and dynamic MRI defecography show equivalent diagnostic performance in assessing pelvic floor disorders. However, because of its better tolerance and availability, dynamic anorectal endosonography may be preferable as the initial imaging procedure after clinical examination in the evaluation of pelvic floor disorders. PMID- 21979186 TI - Diathermy excisional hemorrhoidectomy: a prospective randomized study comparing pedicle ligation and pedicle coagulation. AB - BACKGROUND: In hemorrhoidectomy, pedicle coagulation has been claimed to be associated with less postoperative pain compared with pedicle ligation. OBJECTIVE: This study was designed to compare the effects of pedicle ligation vs pedicle coagulation on postoperative pain in patients undergoing diathermy excisional hemorrhoidectomy. DESIGN: The study was conducted as a single-blind prospective randomized clinical trial. SETTING: Patients were treated at a single tertiary-level teaching hospital (Main University Hospital) in Alexandria, Egypt, from February 2009 to October 2010. PATIENTS: Patients with symptomatic grade III or IV hemorrhoids were eligible. INTERVENTION: Patients were randomly allocated to receive either pedicle coagulation or pedicle ligation during 3-quadrant diathermy excision hemorrhoidectomy. MAIN OUTCOME MEASURES: Patients reported postoperative pain daily on a visual analog scale (0-10, with 10 corresponding to the most severe pain) during the first 10 postoperative days. On-demand parenteral analgesic requirements were recorded during the first 24 hours after surgery. Operative time, postoperative complications, and wound healing rates at 6 weeks postoperatively were also recorded. LIMITATIONS: No a priori power calculation could be performed, so it was not possible to tell whether nonsignificant differences were real or a result of chance. RESULTS: A total of 136 patients were randomly assigned, and 120 patients completed the study (60 in each group). The overall median pain score for the first 10 postoperative days was significantly lower in the pedicle coagulation group than in the pedicle ligation group (4.65 vs 6.56, P < .001), and daily median pain scores were significantly lower for pedicle coagulation than for pedicle ligation throughout the first 6 postoperative days (P < .001). Postoperative pain scores followed different courses in the 2 groups. In the coagulation group, pain levels were lowest during the first 3 postoperative days, increasing from day 4 and then falling after day 8. In the ligation group, pain levels were highest during the first 4 postoperative days, then gradually decreased. The median number of analgesic ampoules required during the first 24 hours was also significantly lower for pedicle coagulation than for ligation: 1 (range, 0-3) vs 3 (range, 1 3); P < .001). The median operative time was 15 (range, 14-20) minutes with coagulation and 14.5 (range, 12-18) minutes with ligation (P < .001). No significant differences were observed in the incidence of postoperative complications or wound healing rates at 6 weeks postoperatively. No anal stenoses or recurrences were observed. CONCLUSIONS: Pedicle coagulation is safe and provides a superior alternative to pedicle ligation by decreasing postoperative pain in the first 6 postoperative days, as well as reducing parenteral analgesic requirements during the first 24 hours postoperatively. PMID- 21979187 TI - Long-term outcomes of human acellular dermal matrix plug in closure of complex anal fistulas with a single tract. AB - BACKGROUND: Bioprosthetic plugs represent a promising technique for the treatment of anal fistula simple because they allow simple and repeatable application, preservation of sphincter integrity, minimal patient discomfort, and subsequent surgical options if needed. However, success rates vary widely. OBJECTIVE: The aim of this study was to assess long-term outcome in patients treated with an acellular dermal matrix plug for closure of complex single-tract anal fistulas. DESIGN: This was a retrospective analysis of a prospective database. SETTING: The study was conducted at a university hospital in Beijing, People's Republic of China. PATIENTS: The study population comprised 114 patients treated between January 2007 and May 2010 for complex high transsphincteric anal fistula with a single tract. INTERVENTION: Fistulas were treated with an acellular dermal matrix plug derived from donated human skin. MAIN OUTCOME MEASURES: The main outcome measures were fistula closure rate and postoperative incontinence (Wexner scores). RESULTS: No mortality or major complications were observed. The overall success rate was 54.4% (62/114), with a median follow-up of 19.5 (range, 11-46) months. Of the 52 patients with plug failure, 11 (21%) had plug extrusion and 9 (17%) had sepsis. Most plug failures occurred within 30 days, with only 1 plug failure occurring 6 months after surgery. On multiple logistic regression analysis, smoking (P < .001), long distance between external opening (P < .001), and performance of the operation by a nonexpert surgeon (P = .018) were significantly associated with plug failure. Of 40 patients who underwent cutting seton placement after plug failure, 33 (82.5%) reported a successful outcome. However, the rate of incontinence 6 months after seton placement was 75% (30/40), whereas the rate in the overall study population 6 months after insertion of the ADM plug was 1.75% (2/114; P < .001). LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS: Given the low morbidity and relative simplicity of the procedure, we suggest that an acellular dermal matrix plug is a reasonable option for closure of complex anal fistulas with a single tract. PMID- 21979188 TI - Evaluation of a new synthetic plug in the treatment of anal fistulas: results of a pilot study. AB - BACKGROUND: The treatment of anal fistulas using plugs is a very promising method because of its simplicity and ability to be carried out on an ambulatory basis. If unsuccessful, it does not compromise subsequent alternative surgical techniques and/or products. However, success rates are variable. OBJECTIVE: This pilot study was designed to investigate the safety and effectiveness of a new synthetic plug in the treatment of transsphincteric anal fistulas. DESIGN: This was a prospective observational study. SETTING: Patients were treated at 2 colorectal surgery centers in Spain (Seville and Huelva). INTERVENTIONS: Anal fistulas were treated with a fistula plug made of bioabsorbable polymers (67% polyglycolide, 33% trimethylene carbonate). PATIENTS: Starting in January 2009, consecutive adult patients with transsphincteric anal fistulas were evaluated. MAIN OUTCOME MEASURES: Outcome measures included rates of successful fistula closure, complications, and continence (Jorge-Wexner incontinence score), assessed postoperatively at 1 week and again at 1, 3, 6, and 12 months. Healing was determined by clinical examination by a surgeon blinded for the intervention. RESULTS: A total of 19 patients (18 men, 1 woman) with transsphincteric anal fistulas were included in the study. The median age was 49 (range, 33-65) years. Of these patients, 12 presented with fistula relapse. The median time from onset of symptoms to surgery was 12 (range, 6-120) months. Three patients had previously placed setons. The follow-up duration was 12 months. Relapse occurred in 16 patients (with a perianal abscess in 1), and successful closure was observed in 3 patients (15.8%). LIMITATIONS: The number of patients was small, and time was needed for the learning curve of the technique. CONCLUSIONS: This study indicates that the new synthetic plug is safe, but the fistula closure rate was low. Randomized studies are needed to further determine the role of the bioabsorbable synthetic plug in the management of anal fistulas. PMID- 21979189 TI - The association between anal function and neural degeneration after preoperative chemoradiotherapy followed by intersphincteric resection. AB - BACKGROUND: Preoperative chemoradiotherapy for rectal cancer is administered to improve local control, but it can also induce severe anal dysfunction after surgery. OBJECTIVE: The goals of the study were to assess the influence of preoperative chemoradiotherapy on pathological findings and to examine the correlation of these findings with the cause of severe anal dysfunction after intersphincteric resection. DESIGN: Peripheral nerve degeneration was evaluated histopathologically with the use of hematoxylin and eosin-stained sections of surgical specimens after intersphincteric resection, based on karyopyknosis, vacuolar degeneration, acidophilic degeneration of cytoplasm, denucleation, and adventitial neuronal changes. Each item was scored to quantify the level of neural degeneration, and the relationship between degeneration and anal function was examined at 12 months after closure of the stoma. Anal function was assessed by questionnaire, and incontinence was evaluated based on the Wexner score. SETTING: This study was conducted at the National Cancer Center Hospital East from 2001 to 2006. PATIENTS: The subjects were 68 patients with lower rectal cancer who underwent intersphincteric resection with (n = 47) or without (n = 21) preoperative chemoradiotherapy. MAIN OUTCOME MEASURES: The findings in the 2 groups were compared to clarify the association between the degree of histological degeneration and postoperative anal function. RESULTS: Neural degeneration was significantly higher in the chemoradiotherapy group, and the neural degeneration and Wexner scores had a significant correlation (P = .003, r = 0.477). CONCLUSION: Preoperative chemoradiotherapy induced marked neural degeneration around the rectal tumor. The significant correlation between the degeneration score and postoperative anal function suggests that this score may be a useful marker to predict the influence of preoperative chemoradiotherapy on anal function after surgery. PMID- 21979190 TI - Congestive heart failure and chronic obstructive pulmonary disease predict poor surgical outcomes in older adults undergoing elective diverticulitis surgery. AB - BACKGROUND: Diverticulitis is a common medical condition that disproportionately affects older adults. The ideal management of recurrent diverticulitis, including the role of prophylactic colectomy, remains uncertain. OBJECTIVE: This study aimed to investigate the outcomes among older patients undergoing elective surgery for diverticulitis and examine subgroups of patients with comorbid congestive heart failure and chronic obstructive pulmonary disease to determine whether outcomes in these patients are worse than in other groups. DESIGN: This article reports a retrospective cohort study of patients undergoing elective surgery for diverticulitis. SETTING: Data were derived from the 100% Medicare Provider Analysis and Review inpatient files from 2004 to 2007. PATIENTS: Included were 22,752 patients, age 65 years and older, with a primary diagnosis of diverticulitis that underwent elective left-colon resection, colostomy, or ileostomy. MAIN OUTCOME MEASURE: The primary outcome measure was in-hospital mortality. The secondary outcome measures were intestinal diversion rates (colostomy and ileostomy) and postoperative complications. RESULTS: Overall mortality, intestinal diversion (colostomy and ileostomy), and postoperative complication rate were 1.2%, 11.3%, and 22.1%. Patients with congestive heart failure had increased odds of in-hospital mortality (OR 3.5, 95% CI 2.59-4.63), colostomy (OR 1.9, 95% CI 1.69-2.27), and all postoperative complications, including hemorrhagic (OR 1.5, 95% CI 1.01-2.11), wound (OR 1.9, 95% CI 1.50 2.39), pulmonary (OR 4.2, 95% CI 3.59-4.85), cardiac (OR 4.6, 95% CI 3.68-5.74), postoperative shock/sepsis (OR 3.2, 95% CI 2.53-4.35), renal (OR 4.1, 95% CI 3.22 5.12), and thromboembolic (OR 1.6, 95% CI 1.00-2.43) complications. Patients with chronic obstructive pulmonary disease had significantly increased odds of wound (OR 1.4, 95% CI 1.19-1.67) and pulmonary (OR 2.2, 95% CI 1.94-2.50) complications. Advancing age, congestive heart failure, and chronic obstructive pulmonary disease were significantly associated with increased morbidity and mortality. LIMITATIONS: Medicare data are limited by the potential for lack of generalizability to patients <65 years and the potential for coding errors. CONCLUSIONS: Elective diverticular surgery in older patients carries substantial morbidity, especially in those patients with comorbid congestive heart failure and chronic obstructive pulmonary disease. The rate of perioperative complications that we document in this patient population may attenuate some of the expected benefit of surgery. PMID- 21979191 TI - Reoperation after colorectal surgery is an independent predictor of the 1-year mortality rate. AB - BACKGROUND: Comparative evaluation of surgical quality among hospitals must improve outcome and efficiency, and reduce medical costs. Reoperation after colorectal surgery is a consequence of surgical complications and therefore considered a quality-of-care indicator. With respect to the mortality rate, the 1 year mortality may be a more meaningful figure than in-hospital mortality, because it also reflects the impact of surgical complications beyond discharge. OBJECTIVE: The aim of our study was to evaluate the 1-year mortality after colorectal surgery and to identify predicting factors. DESIGN: This study was a retrospective analysis from our colorectal surgery database. PATIENTS: All patients who underwent elective colorectal surgery from 2005 to 2008 were included. MAIN OUTCOME MEASURES: Both univariate and multivariate analysis were performed to identify predicting factors. The following variables were analyzed: age, operative risk according to the ASA class, Charlson-Age Comorbidity Index, indication for and type of resection, primary anastomosis, tumor staging, anastomotic leakage, and reoperation. RESULTS: For 743 consecutive patients, the 1-year mortality rate was 6.9%. Patients were operated on mainly because of colorectal cancer (n = 537; 72%). The rate of reoperation and in-hospital mortality was 12.8% and 2.4%. Univariate survival analysis demonstrated that ASA class, age, Charlson-Age Comorbidity Index, reoperation, and stage of disease were independent predictors of 1-year mortality. Multivariate analysis showed that ASA class (P = .020; HR 1.69), age (P = .015; HR 2.08) and reoperation (P = .001; HR 2.72) are directly correlated with 1-year mortality. LIMITATIONS: Both patients with benign diseases and colorectal cancer are included. Furthermore, no clear guidelines on whether to perform a reoperation were available. CONCLUSION: One-year mortality after colorectal surgery is independently predicted by ASA class, age, and reoperation. Our results underline the value of the 1-year mortality rate and the reoperation rate as parameters for quality assessment in colorectal surgery. PMID- 21979192 TI - Postoperative issues of sacral nerve stimulation for fecal incontinence and constipation: a systematic literature review and treatment guideline. AB - BACKGROUND: There is a lack of knowledge on the incidence and management of suboptimal therapeutic effect and the complications associated with sacral nerve stimulation for fecal incontinence and constipation. OBJECTIVE: This study aimed to review current literature on postoperative issues and to propose a treatment algorithm. DATA SOURCE: PubMed, MEDLINE, and EMBASE were searched using the keywords "sacral nerve stimulation," "sacral neuromodulation," "fecal incontinence," and "constipation" for English-language articles published from January 1980 to August 2010. A further search was conducted on a wider literature using the keywords "complication," "adverse effect," "treatment failure," "equipment failure," "infection," "foreign-body migration," "reoperation," "pain," and "algorithm." STUDY SELECTION: Four hundred sixty-one titles were identified, and after a title and abstract review, 135 were subjected to full article review; 89 were finally included in this review. Five articles were added by manual search and consensus. RESULTS: Forty-eight studies were identified as cohort studies reporting on postoperative issues, including 1661 patients who underwent percutaneous nerve evaluation and 1600 patients who proceeded to sacral nerve stimulation therapy. Pooled data showed that the most common problem during percutaneous nerve evaluation was lead displacement (5.3%). The incidence of suboptimal outcome, pain, and infection after implantation was 12.1%, 13.0%, and 3.9%. LIMITATIONS: There was significant underreporting of untoward events, because 60% of the studies did not report complications during percutaneous nerve evaluation, and suboptimal outcome after implantation was not disclosed in 44% of the studies. CONCLUSIONS: The incidence of untoward events associated with sacral nerve stimulation appears to be low. However, there is a significant underreporting of the incidence. Using the information from the structured and systematic literature review, we formulated a clinically relevant guideline for reporting and managing postoperative issues. The guideline can provide a framework for clinical practice. PMID- 21979193 TI - Perineural invasion is a strong and independent predictor of lymph node involvement in colorectal cancer. PMID- 21979196 TI - Fine-needle aspiration cytology of adrenal masses: a re-assessment with histological confirmation. AB - BACKGROUND: Fine-needle aspiration (FNA) of adrenal masses is a method currently indicated in lesions suspected of being extra-adrenal in origin; even though its diagnostic reliability has already been determined in many studies, few have used histological examination obtained after adrenalectomy for diagnostic confirmation. AIM: To analyze the diagnostic performance of adrenal FNA in subjects with an available histological confirmation. SUBJECTS AND METHODS: Fifty subjects (26 benign adrenal lesions, 9 primary malignant lesions, and 15 metastatic lesions) who had undergone ultrasound (US)-guided adrenal FNA and then adrenalectomy were re-analyzed retrospectively. RESULTS: FNA guaranteed a sensitivity of 85.7% and a specificity of 100% in all subjects; after having divided the subjects into oncologic and non-oncologic groups, the sensitivity of the test in oncologic patients (100%) increased significantly compared to non oncologic (57.1%) with no difference in specificity (100% in both groups). Considering also non-diagnostic samples in our analysis (no.=11; 22% of all samples studied), FNA correctly diagnosed malignancy only in 75% of the cases and benignancy only in 66.6%; however, even after including non-diagnostic samples, the percentage of correct malignancy diagnosis remained significantly higher in oncologic (93.3%) than in non-oncologic patients (44.4%) without significant statistical difference between the 2 groups regarding the percentage of correct benignancy diagnosis (respectively 100% and 63.6%). CONCLUSIONS: Our study, based on histological confirmation, underlines the low discriminant value of US-guided adrenal FNA, though the method may have value in oncologic patients. PMID- 21979198 TI - Increased levels of stress and burnout are related to decreased physician experience and to interventional gastroenterology career choice: findings from a US survey of endoscopists. AB - OBJECTIVES: Physician stress and burnout can decrease job satisfaction, increase medical errors, and reduce quality of life. Gastrointestinal endoscopic practice is increasing in complexity, with an associated increase in complications. These factors may result in more stress and burnout in younger gastroenterologists (GEs) and interventional GEs (IGEs) who perform more complex endoscopic procedures. We aimed to create a valid measure of GE endoscopic practice stress and to evaluate stress and burnout related to endoscopist experience and IGE versus non-IGE practice. METHODS: We used both a qualitative and a cross sectional correlation design. Semistructured interviews were conducted and thematically coded to create a measure of stressors in GE practice, the Gastroenterologist Stress Inventory (GESI). Gastroenterology fellows and attending physicians were approached to participate. Four GEs were interviewed, and 489 completed the online survey. Endoscopists completed the Maslach Burnout Inventory, the GESI, and demographic, training, and practice data. RESULTS: The GESI met reliability standards. Junior IGEs and junior non-IGEs reported more stress related to endoscopic practice than senior attendings. All GEs reported moderate levels of burnout; decreased physician experience was a predictor of burnout for IGEs. CONCLUSIONS: GEs report moderate levels of stress and burnout. IGEs and those who have experienced an endoscopic complication report significantly more stress. Less experience is related to more stress and burnout, with junior IGEs reporting the highest levels. PMID- 21979199 TI - Improving access to colorectal cancer screening through medical philanthropy: feasibility of a flexible sigmoidoscopy health fair for uninsured patients. AB - OBJECTIVES: Only half of eligible patients in the United States undergo colorectal cancer (CRC) screening as recommended. Hypothesizing that the medical philanthropy platform may be effective in improving access to CRC screening, we aimed to demonstrate the feasibility of a flexible sigmoidoscopy (FS)-based CRC screening "health fair" for uninsured patients. METHODS: Uninsured patients older than 50 years who had not undergone CRC screening in the preceding 10 years were recruited through local free clinics and health fairs. A standard medical clinic was transformed into a fully functional endoscopy unit. Medicolegal protection for volunteers was obtained through the Florida Department of Health's Volunteer Health Care Provider Program. Unsedated FS with polypectomy was performed. Those with high-risk endoscopic features were given instructions on obtaining a full colonoscopy. RESULTS: Fifty-two patients without access to any form of CRC screening underwent FS. Ninety-four percent had an adequate bowel preparation, although 40% required on-site enema. Eighteen patients had a total of 22 polyps, 4 of which were adenomatous. There were no complications. The total cost of the fair, excluding donated resources such as endoscopes and processors, was $6,531.47, amounting to $126 per patient screened. CONCLUSIONS: Health fair-style CRC screening for uninsured patients is feasible. With improved efficiency, widespread application of CRC screening using the medical philanthropy platform may represent a viable approach to reducing the underuse of CRC screening among the uninsured. PMID- 21979203 TI - Editorial: Measurement of HBsAg concentration during antiviral therapy of hepatitis B: who, when, and why. AB - The measurement of hepatitis B surface antigen (HBsAg) concentration in serum is now under evaluation in treatment trials for hepatitis B. HBsAg kinetics differ during interferon and nucleoside analog treatment. A rapid decline in HBsAg concentration during interferon therapy has been associated with a higher chance for sustained virological response. By contrast, a much slower decline often occurs during nucleoside analog therapy and limits the ability of this test to be a useful prognostic indicator during the first year or two of treatment. PMID- 21979206 TI - Editorial: fluid resuscitation in acute pancreatitis: striking the right balance. AB - Fluid resuscitation is a key component of the early management of acute pancreatitis. Current clinical practice guidelines recommend aggressive fluid resuscitation despite limited prospective data. In this month's issue of the American Journal of Gastroenterology, de-Madaria et al. present findings from a prospective cohort study that evaluate the relationship between early resuscitation parameters and several important outcome measures. Their findings challenge several of our long held beliefs regarding the benefits of vigorous fluid resuscitation in the early phase of acute pancreatitis. Findings from this study along with several others now suggest that a more tailored approach to resuscitation is needed. PMID- 21979207 TI - The risk of multiplying diagnostic combinations in the absence of a perfect gold standard for a fibrosis test. PMID- 21979209 TI - Impact of display alternatives in the determination of bolus handling: a study using high-resolution manometry with impedance. PMID- 21979212 TI - Efficacy of 5-aminosalicylates for the maintenance of remission in Crohn's disease. PMID- 21979213 TI - Elevated serum ghrelin levels in adult patients with cyclic vomiting syndrome. PMID- 21979214 TI - Relationship between serum angiopoietin-2 level and perfusion CT parameters in severe acute pancreatitis. PMID- 21979215 TI - Triple gallbladder: a rare entity. PMID- 21979216 TI - Diagnosis of bilateral adrenal metastases secondary to malignant melanoma by EUS guided FNA. PMID- 21979217 TI - Splenic littoral cell hemangioendothelioma in a patient with Crohn's disease previously treated with immunomodulators and anti-TNF agents: a rare tumor linked to deep immunosuppression. PMID- 21979218 TI - Could trastuzumab suppress hepatitis C virus in a patient with chronic hepatitis and breast cancer? PMID- 21979221 TI - [Special considerations in breast cancer treatment of an augmented breast]. AB - Breast augmentation surgery involving the use of implants has been one of the most popular plastic surgical procedures for decades. As the multi-million female population who received breast implants ages, the risk of cancer is increasing rapidly, therefore the incidence of malignant disease in association with breast implants will increase as well. Although there is no relationship between tumor development and implants, these cases require special considerations in diagnostics, therapy and follow-up methods. Appropriate multidisciplinary treatment of tumors in augmented breasts corresponding with modern oncoplastic principles can only be accomplished based on adequate oncological, breast and plastic surgical knowledge. Supposing a possible increase of this condition in Hungary, too, authors provide a wide review of the literature on the special oncological and esthetic considerations, for the first time in Hungarian language. PMID- 21979222 TI - ["Constantly rising or peaks and plateaus?" Incidence of childhood type 1 diabetes in Hungary (1989-2009)]. AB - Aim of this study was to examine secular trends in the incidence of type 1 diabetes in children aged 0-14 years in Hungary over the period 1989-2009. METHODS: Newly diagnosed children with type 1 diabetes aged 0-14 years in Hungary were prospectively registered from 1989 to 2009. Standardized incidence rates were calculated and secular trends were estimated using Poisson regression analysis. RESULTS: Between 1989 and 2009 a total number of 3432 children were identified, giving a standardized incidence rate of 12.5 (95%CI 12.1-12.9) per 100 000 person/year. The overall incidence rate has doubled from 7.7 (95%CI 6.4 9.15) per 100 000 per year in 1989 to 18.2 (95%CI 15.7-20.9) per 100 000 per year in 2009. A significant linear trend in incidence (p<0.001) has been observed over time, with a mean annual increase of 4.4%. The increase in incidence was present in both genders and in all age groups, with the largest relative increase in the youngest age group (6.2%; p<0.001). CONCLUSION: The incidence of type 1 diabetes in Hungarian children continues to increase, with the highest rate in the very young. PMID- 21979223 TI - [Frequency and antibiotic resistance of Ureaplasma urealyticum and Mycoplasma hominis in genital samples of sexually active individuals]. AB - Ureaplasma urealyticum and Mycoplasma hominis have important role among the causative agents of sexually transmitted diseases. AIM: The aim of the study was to determine the frequency and antibiotic resistance of Ureaplasma urealyticum and Mycoplasma hominis in genital samples obtained from patients examined in the Sexually Transmitted Diseases Centre of the Department of Dermatology, Venerology and Dermatooncology, Semmelweis University, Budapest between May 1, 2008 and July 31, 2010. PATIENTS AND METHODS: Samples were taken from the urethra in men and from the cervix and urethra in women by universal swab (Biolab(r)) into Urea-Myco DUO kit (Bio-Rad(r)) and were incubated for 48 hours at 37 C degrees . Antibiotic sensitivity of positive samples was determined in U9 bouillon using SIR Mycoplasma kit (Bio-Rad(r)). RESULTS: Samples for 4154 patients aged 16-60 years were examined. In 247/4154 samples (6%) U. urealyticum and in 26/4154 samples (0.63%) M. hominis was isolated from the genital tract. Most U. urealyticum and M. hominis strains (75% and 77%, respectively) were cultured from cervix, while the remaining 25%, and 23% from the male and female urethra, respectively. U. urealyticum and M. hominis were most commonly detected in patients aged between 21 and 40 years. The majority of U. urealyticum strains were sensitive to tetracycline (94%), doxycycline (95%), azithromycin (88%) and josamycin (90%), but were resistant to ofloxacin (21%), erythromycin (85%) and clindamycin (79%). Seventy-seven percent of the U. urealyticum strains were simultaneously resistant to erythromycin and clindamycin, suggesting that ex iuvantibus therapies may select cross-resistant strains to both antibiotics. The resistance of M. hominis to clindamycin, doxycycline, ofloxacin and tetracycline varied between 4% and 12 %. CONCLUSIONS: Because none of the strains was sensitive to all examined antibiotics, the antibiotic sensitivity of U. urealyticum and M. hominis strains should be determined. The high rate of ofloxacin, erythromycin and clindamycin resistance should be considered in the therapy of U. urealyticum infections in Hungary. This is the first such a clinical microbiological study in this topic in Hungary. PMID- 21979224 TI - [Thrombosis of the jugular vein during pregnancy]. AB - Thrombosis of the jugular vein is a rare complication during pregnancy. In most cases the thrombogenic factor was ovarian hyperstimulation syndrome occurred during the process of assisted reproductive technology or inherited or acquired thrombophilia. Authors report a case of jugular vein thrombosis occurred after in vitro fertilization. On the basis of the literature thromboprophylaxis should be indicated for patients who develop ovarian hyperstimulation syndrome, and also be considered for women with inherited or acquired thrombophilia, while undergoing assisted reproductive techniques. PMID- 21979225 TI - [Yawning, sleep and dream]. PMID- 21979228 TI - Democratizing nanotech, then and now. PMID- 21979229 TI - Back to the future. PMID- 21979231 TI - Molecular motors: Powered by electrons. PMID- 21979232 TI - Graphene optoelectronics: Plasmons get tuned up. PMID- 21979233 TI - Electron spectroscopy: a new window opens. PMID- 21979234 TI - Environmental, health and safety issues: Nanoparticles in the real world. PMID- 21979235 TI - Generation of iPS cells using a BacMam multigene expression system. AB - Generation of iPS cells from mouse embryonic fibroblasts (MEF) was achieved using a BacMam transduction system containing a polycistronic plasmid expression vector for coincident and optimized expression of four defined reprogramming transcription factors. The sequences for Oct4, Klf4, Sox2 and c-Myc, were cloned as a fusion gene (OKSM) in a single open reading frame (ORF) via self-cleaving 2A peptides and expressed under the control of the CAG promoter. The transduction efficiency of primary MEF cells with BacMam particles carrying CAG-directed Venus reporter gene is 64-98%. After three successive transductions (at intervals of 3 days) of MEF cells with BacMam particles carrying a OKSM or OSKM cassette, the iPS cell colonies are observed in 15-24 days. A single transduction of MEF cells is also effective in generating sufficiently reprogrammed iPS cell lines. The iPS cell lines from colonies picked were positively stained by Nanog, SSEA-1 immunofluorescence and alkaline phosphatase substrate markers. The advantage of using the EOS-S(4+)-EmGFP reporter to identify sufficiently reprogrammed iPS cell lines is discussed by representing experimental results obtained with electroporated plasmids, such as a mixture of 2 tandem OS and KM plasmids and a polycistronic OKSM expression plasmid. PMID- 21979236 TI - Regulation of intestinal stem cell proliferation by human methyl-CpG-binding protein-2 in Drosophila. AB - Recent studies have suggested the involvement of epigenetic factors such as methyl-CpG-binding protein-2 (MeCP2) in tumorigenesis. In addition, cancer may represent a stem cell-based disease, suggesting that understanding of stem cell regulation could provide valuable insights into the mechanisms of tumorigenesis. However, the function of epigenetic factors in stem cell regulation in adult tissues remains poorly understood. In the present study, we investigated the role of human MeCP2 (hMeCP2), a bridge factor linked to DNA modification and histone modification, in stem cell proliferation using adult Drosophila midgut, which appears to be an excellent model system to study stem cell biology. Results show that enterocyte (EC)-specific expression of hMeCP2 in adult midgut using an exogenous GAL4/UAS expression system induced intestinal stem cell (ISC) proliferation marked by staining with anti-phospho-histone H3 antibody and BrdU incorporation assays. In addition, hMeCP2 expression in ECs activated extracellular stress-response kinase signals in ISCs. Furthermore, expression of hMeCP2 modulated the distribution of heterochromatin protein-1 in ECs. Our data suggests the hypothesis that the expression of hMeCP2 in differentiated ECs stimulates ISC proliferation, implying a role of MeCP2 as a stem cell regulator. PMID- 21979237 TI - Evaluation of a new nanoparticle-based lateral-flow immunoassay for the exclusion of heparin-induced thrombocytopenia (HIT). AB - Heparin-induced thrombocytopenia (HIT) is an adverse complication of heparin caused by HIT antibodies (abs) that recognise platelet factor 4-heparin (PF4/hep) complexes. Several laboratory tests are available for the confirmation and/or refutation of HIT. A reliable and rapid single-sample test is still pending. It was the objective of this study to evaluate a new lateral-flow immunoassay based on nanoparticle technology. A cohort of 452 surgical and medical patients suspected of having HIT was evaluated. All samples were tested in two IgG specific ELISAs, in a particle gel immunoassay (PaGIA) and in a newly developed lateral-flow immunoassay (LFI-HIT) as well as in a functional test (HIPA). Clinical pre-test probability was determined using 4T's score. Platelet activating antibodies were present in 34/452 patients, all of whom had intermediate to high clinical probability. PF4/hep abs were detected in 79, 87, 86, and 63 sera using the four different immunoassays. The negative predictive values (NPV) were 100% for both ELISA tests and LFI-HIT but only 99.2% for PaGIA. There were less false positives (n=29) in the LFI-HIT compared to any other test. Additionally, significantly less time was required to perform LFI-HIT than to perform the other immunoassays. In conclusion, a newly developed lateral-flow assay, LFI-HIT, was capable of identifying all HIT patients in a cohort in a short period of time. Beside an NPV of 100%, the rate of false-positive signals is significantly lower with LFI-HIT than with other immunoassay(s). These performance characteristics suggest a high potency in reducing the risk and costs in patients suspected of having HIT. PMID- 21979238 TI - [Physiotherapeutic and training therapeutic options for instable patellofemoral joints]. AB - In order to allow an adequate and timely restoration of physical performance with an instable patellofemoral joint within the framework of complex therapy strategies, individual post-traumatic cause-and-effect chains and their influence on the hip-leg axis of both the active and passive musculoskeletal systems must be considered as well as joint-specific aspects. For this reason selected relevant neurophysiological aspects of one and multiple joint movement stereotypes will be firstly presented. Subsequently some selected physiotherapeutic measures will be presented and their indication-specific relevance will be explained. To round up, training therapeutic measures under special consideration of tension and control-oriented aspects will be summarized. For the first time possible individual measures of physical therapy, physiotherapy and training therapy will be combined on a time-function basis.Patients with knee problems involving the patellofemoral joint have in most cases injuries to the musculoskeletal system with an orthopedic traumatological focus which diminishes the functional ability and efficiency of the musculoskeletal system of the complete lower extremities. As a rule no special therapy techniques are used but patients can be adequately helped by a qualified therapist with a portfolio of therapeutic techniques to effect an alleviation or improvement of the complaints following medical treatment (conservative or surgical). However, for problems involving the patellofemoral joint axis-specific aspects of the hip-leg axis must be considered in addition to joint-specific aspects. PMID- 21979239 TI - [Treatment of patellar instability in children and adolescents]. AB - To address recurrent patellar instability in children and young adolescents a variety of therapeutic options exist either as non-operative or operative treatment. Recent options, such as reconstruction of the medial patellofemoral ligament have evoked a new focus of attention on this topic. The intention of this article is to present diverse therapeutic options and to evaluate them by reference to the current literature. PMID- 21979241 TI - Effects of manganese deficiency and added cerium on photochemical efficiency of maize chloroplasts. AB - The mechanism of the fact that manganese deprivation and cerium addition affect the photochemical efficiency of plants is unclear. In this study, we investigated the improvement by cerium of the damage of the photochemical function of maize chloroplasts under manganese-deprived stress. Chlorophyll fluorescence induction measurements showed that the ratio of variable to maximum fluorescence (Fv/Fm) underwent great decreases under manganese deficiency, which was attributed to the reduction of intrinsic quantum efficiency of the photosystem II units. The electron flow between the two photosystems, activities of Mg(2+)-ATPase and Ca(2+)-ATPase, and rate of photophosphorylation on the thylakoid membrane of maize chloroplasts were reduced significantly by exposure to manganese deprivation. Furthermore, the inhibition of cyclic photophosphorylation was more severe than non-cyclic photophosphorylation under manganese deficiency. However, added cerium could relieve the inhibition of the photochemical reaction caused by manganese deprivation in maize chloroplasts. It implied that manganese deprivation could disturb photochemical reaction of chloroplasts strongly, which could be improved by cerium addition. PMID- 21979242 TI - Impact of bulk and nanosized titanium dioxide (TiO2) on wheat seed germination and seedling growth. AB - The impacts of different concentrations of bulk and nanosized TiO(2) on seed germination and seedling growth of wheat were studied in a randomized completely design with four replications in the College of Agriculture, Ferdowsi University of Mashhad, Iran, in 2011. The experimental treatments included five concentrations of bulk (1, 2, 10, 100, and 500 ppm), five concentrations of nanosized TiO(2) (1, 2, 10, 100, and 500 ppm), and control (without any TiO(2)). Results indicated that among the wheat germination indices, only mean germination time was affected by treatments. The lowest and the highest mean germination time (0.89 vs. 1.35 days) were obtained in 10 ppm concentration of nanosized TiO(2) and control treatments, respectively. In addition, shoot length, seedling length, and root dry matters were affected by bulk and nanosized TiO(2) concentrations, significantly. Shoot and seedling lengths at 2 and 10 ppm concentrations of nanosized TiO(2) were higher than those of the untreated control and bulk TiO(2) at 2 and 10 ppm concentrations. Employing nanosized TiO(2) in suitable concentration could promote the seed germination of wheat in comparison to bulk TiO(2) but in high concentrations had inhibitory or any effect on wheat. PMID- 21979243 TI - Serum iron, zinc, and copper concentration in premature graying of hair. AB - Premature graying of hair with unclear etiology, which is known as premature canities, is a common cause of referrals to the dermatologists. We assessed the relationship between serum iron, copper, and zinc concentrations with premature canities. This study was conducted on patients under 20 years old suffering from premature canities, having a minimum of ten gray hair fibers, and referring to university hospitals of Isfahan (Iran). The results were compared with age-sex matched controls. Demographic data and disease characteristics were recorded for two groups. We studied serum iron, copper, and zinc concentrations of 66 patients and 66 controls using atomic absorption and Ferrozine methods. The mean age of studied cases was 17.8 +/- 2.0 years, and the mean age of the onset of canities was 15.5 +/- 3.2 years with no significant difference between males and females (P > 0.05). Serum copper concentration was significantly lower in patients compared with controls (90.7 +/- 37.4 vs. 105.3 +/- 50.2 MUg/dL, P = 0.048), but serum iron concentration was significantly lower in controls compared to patients (88.8 +/- 39.5 vs. 108.3 +/- 48.4 MUg/dL, P = 0.008). Also, there was no significant difference between patients and controls in serum zinc concentration (114.8 +/- 67.8 vs. 108.2 +/- 49.9 MUg/dL, P = 0.285). According to these results, among copper, zinc, and iron, a low serum copper concentration may play a role in premature graying of hairs in our society. Further studies are needed to find the underlying mechanism of this relationship. PMID- 21979244 TI - The prevalence of hearing impairment and its burden on the quality of life among adults with Medicare Supplement Insurance. AB - PURPOSE: To estimate the impact of hearing impairment on quality of life from a physical and mental standpoint. METHODS: Data were obtained from the Health Update Survey, which contains questions on demographics, comorbid conditions, and the Veterans RAND 12-item health status/quality of life survey. It was fielded on a random sample of 15,000 adults with an AARP((r)) Medicare Supplement plan, insured by UnitedHealthcare. Respondents were divided into those with hearing impairments and others, based on their response to a survey question. Univariate and multivariate analyses were conducted to estimate the likelihood of hearing impairment and its impact on quality of life while controlling for respondent demographics and comorbid conditions. RESULTS: Of the 5,515 eligible respondents, 10.4% reported having hearing impairments. The strongest predictor of hearing impairment was older age, while those with 4 years of college or more were least likely to have hearing impairments. Those with hearing impairments averaged significantly lower physical component and mental component scores, exceeding those of numerous other chronic conditions. CONCLUSIONS: This is the first known study of hearing impairment among those with Medigap coverage. Hearing impairment was strongly associated with lower quality of life from both a physical and mental health standpoint. PMID- 21979246 TI - Mechanism of silver- and copper-catalyzed decarboxylation reactions of aryl carboxylic acids. AB - Silver- and copper-catalyzed decarboxylation reactions of aryl carboxylic acids were investigated with the aid of density functional theory calculations. The reaction mechanism starts with a carboxylate complex of silver or copper. Decarboxylation occurs via ejecting CO(2) from the carboxylate complex followed by protodemetallation with an aryl carboxylic acid molecule to regenerate the starting complex. Our results indicated that the primary factor to affect the overall reaction barriers is the ortho steric destabilization effect on the starting carboxylate complexes for most cases. Certain ortho substituents that are capable of coordinating with the catalyst metal center without causing significant ring strain stabilize the decarboxylation transition states and reduce the overall reaction barriers. However, the coordination effect is found to be the secondary factor when compared with the ortho effect. PMID- 21979247 TI - Mutant enrichment with 3'-modified oligonucleotides a practical PCR method for detecting trace mutant DNAs. AB - Many clinical situations necessitate highly sensitive and reliable molecular assays; however, the achievement of such assays remains a challenge due to the inherent limitations of molecular testing methods. Here, we describe a simple and inexpensive enrichment technique that we call mutant enrichment with 3'-modified oligonucleotides (MEMO). The method is based on the use of a 3'-modified oligonucleotide primer that blocks extension of the normal allele but enables extension of the mutated allele. The performance of the technique was evaluated with respect to its ability to detect common cancer mutations in the EGFR, KRAS, BRAF, TP53, JAK2, and NPM1 genes. We achieved sensitivities of 10(-2) to 10(-6) using downstream Sanger sequencing, depending on the concentrations and thermodynamics of the primers. MEMO may be applicable to the quantitative real time PCR platform and other downstream assays. This technique may be practically applicable to various medical situations. PMID- 21979248 TI - Molecular characterization of peste des petits ruminants virus from the Karamoja region of Uganda (2007-2008). AB - Antibodies against peste des petits ruminants virus (PPRV) were first detected in goats in East Africa in 1995 without any clinical disease. It was not until during the years 2006 and 2007 that the disease outbreaks were first reported in Kenya and Uganda, respectively. This study was carried out to detect and characterize PPRV from a suspected outbreak in sheep and goats in the Karamoja region in 2007-2008. Oculo-nasal and blood samples were tested using F-gene-based primers, and their genetic relationships to other sequences in the GenBank database were investigated. A total of 383 samples suspected to contain PPRV were randomly collected and tested. Sixty-seven (17.5%) were positive when F protein gene primers were used. During the years 2007 and 2008, 38.1% (26/67) and 13.0% (41/316) of samples were positive by PCR, respectively. The 2007 sequences clustered with Asian sequences in lineage 4 and Cote d'Ivoire 86 (ICV 86) in lineage 2, while all of the 2008 samples clustered in lineage 1. Over the years, the implicated strains were genetically close (88%-91%) to the vaccine strain (Nig 75/1). Based on this study, the circulating PPR strains in Uganda are heterogeneous, and therefore, the disease may have been introduced from different sources. PMID- 21979249 TI - Sodium Tripolyphosphate: an excipient with intrinsic in vitro anti-Candida activity. AB - Sodium Tripolyphosphate (STPP) is a food additive that is being used in the development of micro and nanoparticles as it induces ionic interactions with chitosan molecules. Although the ability of STPP to inhibit the growth of several food contaminants has been reported, studies on its activity against clinical isolates are scarce. Candida spp. are common causative agents of mucocutaneous infections including the vulvovaginal tegument and new therapeutic approaches are needed in order to treat resistant and recurrent cases. The aim of this study was to evaluate in vitro both antifungal (anti-Candida spp.) activity, and cytotoxicity, on human dermal fibroblasts, of STPP solutions. STPP showed an inhibitory species-dependent activity against several Candida spp. strains being particularly active on C. glabrata, followed by C. guilliermondii. In vitro, STPP showed a concentration dependent cytotoxicity. Therefore STPP use, in low concentrations, seems to be interesting in the development of drug delivery systems for the treatment of vulvovaginal candidosis. PMID- 21979250 TI - Physicochemical characterization techniques for lipid based delivery systems for siRNA. AB - siRNA based therapeutics is an emerging class of molecules with a high potential for fulfilling the promise of gene medicine. The high selectivity of siRNAs for their targets and subsequent gene ablation has been effectively demonstrated in a wide range of pre-clinical models. siRNA delivery in vivo has been most successfully achieved using lipid-based drug delivery systems. These lipid based formulations are designed to entrap siRNA molecules, ensure stability in in vitro and in vivo milieu, facilitate uptake, enhance cellular targeting, and facilitate delivery in the desired intracellular compartment. As more siRNA-based therapeutics enters the clinic with the associated regulatory scrutiny, there is a clear need to develop well-characterized systems that ensure consistent quality and thus reliable performance. Early clinical trials can be conducted using formulations with limited short-term stability manufactured on a small scale. However, a thorough understanding of the factors that influence the structure and stability of these particulate formulations is required to prevent any issues with optimization of large-scale industrial manufacturing, scale-up, and long term shelf-life required to support large clinical trials and eventual market use. As newer targets for siRNA are identified and novel lipids are synthesized to optimize their in vivo efficiency, concomitant development of bio-physical methodologies that can improve understanding of the assembly and stability of these complex systems is critical. Along with bio-physical characterization, these assays are also required to reliably design, screen, develop and optimize formulations. Physicochemical characterization thus forms the basis of developing an effective analytical control strategy for siRNA delivery systems. In this review, analytical techniques used to characterize lipid-based siRNA delivery systems are discussed in detail. The importance of these physicochemical characterization techniques and analytical assays is explained. Case studies illustrating their use in siRNA formulation development and optimization are presented. PMID- 21979251 TI - Chimeric advanced drug delivery nano systems (chi-aDDnSs) for shikonin combining dendritic and liposomal technology. AB - The interest of drug delivery has focused on the creation of new formulations with improved properties, taking much attention to the drug release from the carrier. Liposomes have already been commercialized, while dendrimers and hyperbranched polymers are emerging as potentially ideal drug delivery vehicles. Chimeric advanced drug delivery nano systems (chi-aDDnSs) are mixed nanosystems combining different biomaterials that can offer advantages as drug carriers. Alkannin and shikonin (A/S) are naturally occurring hydroxynaphthoquinones with a well-established spectrum of wound healing, antimicrobial, anti-inflammatory, antioxidant and recently established antitumor activity. In this work three generations of hyperbranched aliphatic polyesters were used for the first time to form complexes with shikonin, as well as liposomal chi-aDDnSs. Characterization of the shikonin-loaded chi-aDDnSs was performed by measuring their particle size distribution, zeta-potential, drug encapsulation efficiency and the in vitro release profile. The analysis revealed sufficient drug encapsulation and appropriately featured release profiles. Chi-aDDnSs were also examined for their physical stability at 4 degrees C. The results are considered promising and could be used as a road map for designing in vivo experiments. PMID- 21979252 TI - In vivo transfection study of chitosan-DNA-FAP-B nanoparticles as a new non viral vector for gene delivery to the lung. AB - Gene therapy targeted at the respiratory epithelium holds therapeutic potential for diseases such as cystic fibrosis and lung cancer. We recently reported that Chitosan-DNA-FAP-B nanoparticles are good candidates for targeted gene delivery to fibronectin molecules (FAP-B receptors) of lung epithelial cell membrane. In this study Chitosan-DNA-FAP-B nanoparticles were nebulized to mice using air jet nebulizer. The effect of nebulization on size, zeta potential and DNA binding ability of nanoparticles were studied. The level of gene expression in the mice lungs was evaluated. Nebulization did not affect the physicochemical properties of nanoparticles. Aerosol delivery of Chitosan-DNA-FAP-B nanoparticles resulted in 16-fold increase of gene expression in the mice lungs compared with Chitosan DNA nanoparticles. This study suggested that Chitosan-FAP-B nanoparticle can be a promising carrier for targeted gene delivery to the lung. PMID- 21979253 TI - Didactic CME and practice change: don't throw that baby out quite yet. AB - Skepticism exists regarding the role of continuing medical education (CME) in improving physician performance. The harshest criticism has been reserved for didactic CME. Reviews of the scientific literature on the effectiveness of CME conclude that formal or didactic modes of education have little or no impact on clinical practice. This has led some to argue that didactic CME is a highly questionable use of organizational and financial resources, and a cause of lost opportunities for physicians to engage in meaningful learning. The authors' current program of research has forced them to reconsider the received wisdom regarding the relationship between didactic modes of education and learning, and the role frank dissemination can play in bringing about practice change. The authors argued that the practice of assessing and valuing educational methods based only on their capacity to directly influence practice reflects an impoverished understanding of how change in clinical practice actually occurs. Drawing on case studies research, examples were given of the functions didactic CME served in the interest of improved practice. Reasons were then explored as to why the contribution of didactic CME is often missed or dismissed. The goal was not to advocate for a return to the status quo ante where lecture-based education is the dominant modality, but rather to acknowledge both the limits and potential of this longstanding approach to delivering continuing education. PMID- 21979254 TI - Purification of human respiratory syncytial virus fusion glycoprotein. AB - Human respiratory syncytial virus (RSV) fusion glycoprotein (F) elicits neutralizing antibodies to RSV and has therefore attracted much attention as a suitable candidate antigen in the development of gene-based vaccines against RSV infections. However, a major obstacle in vaccine development has been the problem of antigen purification. To address this problem, we have developed a new method that combines sucrose gradient ultracentrifugation and a two-step chromatographic process, to purify RSV F from RSV particles propagated in HEp-2 cells. Analysis of the fractions produced using this method showed recovery of a functional homodimer with a molecular weight of 140 kDa, and 54% preservation of the original F. PMID- 21979271 TI - Using MeSH (medical subject headings) to enhance PubMed search strategies for evidence-based practice in physical therapy. AB - BACKGROUND: Evidence-based practice (EBP) is an important paradigm in health care. Physical therapists report lack of knowledge and time constraints as barriers to EBP. OBJECTIVE: The purpose of this technical report is to illustrate how Medical Subject Headings (MeSH), a controlled vocabulary thesaurus of indexing terms, is used to efficiently search MEDLINE, the largest component of PubMed. Using clinical questions, this report illustrates how search terms common to physical therapist practice do or do not map to appropriate MeSH terms. A PubMed search strategy that takes advantage of text words and MeSH terms is provided. RESULTS: A search of 139 terms and 13 acronyms was conducted to determine whether they appropriately mapped to a MeSH term. The search results were categorized into 1 of 5 outcomes. Nearly half (66/139) of the search terms mapped to an appropriate MeSH term (outcome 1). When a search term did not appropriately map to a MeSH term, it was entered into the MeSH database to search for an appropriate MeSH term. Twenty-one appropriate MeSH terms were found (outcomes 2 and 4), and there were 52 search terms for which an appropriate MeSH term was not found (outcomes 3 and 5). Nearly half of the acronyms did not map to an appropriate MeSH term, and an appropriate MeSH term was not found in the database. LIMITATIONS: The results are based on a limited number of search terms and acronyms. CONCLUSIONS: Understanding how search terms map to MeSH terms and using the PubMed search strategy can enable physical therapists to take full advantage of available MeSH terms and should result in more-efficient and better informed searches. PMID- 21979255 TI - [Psoriatric arthritis - a permanent challenge for rheumatologists and patients: part 2: imaging diagnostics, classification and therapy]. AB - In recent years a considerable number of imaging techniques have been used to demonstrate the onset and progression of arthritis-related changes in psoriatric arthritis (PsA). Moreover the identification of new immunological pathways has resulted in a substantial improvement of available therapies for PsA increasing the chance for the individual to receive effective treatment. Although an all embracing disease activity score is still lacking, there is a variety of symptom related tools to adequately reflect the course of disease and to evaluate the corresponding treatment success. This manuscript aims to give an overview of the latest corresponding knowledge with respect to PsA. PMID- 21979272 TI - Effectiveness of a targeted exercise intervention in reversing older people's mild balance dysfunction: a randomized controlled trial. AB - BACKGROUND: Previous research has mainly targeted older people with high risk of falling. The effectiveness of exercise interventions in older people with mild levels of balance dysfunction remains unexplored. OBJECTIVE: This study evaluated the effectiveness of a home balance and strength exercise intervention in older people systematically screened as having mild balance dysfunction. DESIGN: This was a community-based, randomized controlled trial with assessors blinded to group allocation. PARTICIPANTS: Study participants were older people who reported concerns about their balance but remained community ambulant (n=225). After a comprehensive balance assessment, those classified as having mild balance dysfunction (n=165) were randomized into the trial. INTERVENTION: Participants in the intervention group (n=83) received a 6-month physical therapist-prescribed balance and strength home exercise program, based on the Otago Exercise Program and the Visual Health Information Balance and Vestibular Exercise Kit. Participants in the control group (n=82) continued with their usual activities. OUTCOME MEASURES: Laboratory and clinical measures of balance, mobility, and strength were assessed at baseline and at a 6-month reassessment. RESULTS: After 6 months, the intervention group (n=59) significantly improved relative to the control group (n=62) for: the Functional Reach Test (mean difference=2.95 cm, 95% confidence interval [CI]=1.75 to 4.15), the Step Test (2.10 steps/15 seconds, 95% CI=1.17 to 3.02), hip abductor strength (0.02, 95% CI=0.01 to 0.03), and gait step width (2.17 cm, 95% CI=1.23 to 3.11). There were nonsignificant trends for improvement on most other measures. Fourteen participants in the intervention group (23.7%) achieved balance performance within the normative range following the exercise program, compared with 3 participants (4.8%) in the control group. LIMITATIONS: Loss to follow-up (26.6%) was slightly higher than in some similar studies but was unlikely to have biased the results. CONCLUSIONS: A physical therapist-prescribed home exercise program targeting balance and strength was effective in improving a number of balance and related outcomes in older people with mild balance impairment. PMID- 21979273 TI - Prospective study of the incidence and predictors of thrombus in children undergoing palliative surgery for single ventricle physiology. AB - PURPOSE: To determine the incidence and clinical and biomarker predictors of perioperative thrombosis in children with single ventricle physiology undergoing staged palliation. METHODS: Nineteen patients were enrolled and 16 completed the study. Serial ultrasounds of the central venous system were performed to evaluate for thrombus. Plasma antithrombin III, thrombin-antithrombin complex, protein C, protein S, tissue factor pathway inhibitor, plasminogen activator inhibitor-1, tissue plasminogen activator antigen, D-dimer, soluble CD40 ligand, and urinary thromboxane were measured serially before and after surgery. Cardiopulmonary bypass time, aortic cross clamp time, blood product administration, inotrope score, chest tube output, cardiac function by echocardiography, intensive care unit and hospital lengths of stay, and central venous catheter days were recorded. RESULTS: The incidence of perioperative thrombus was 31%. Patients who developed a thrombus had poorer preoperative ventricular function (p = 0.03) and longer cardiopulmonary bypass times (p = 0.03) than those who did not develop a thrombus. Preoperative plasma antithrombin III was lower (p = 0.01) and tissue plasminogen activator antigen concentrations were higher (p = 0.02) in patients with a thrombus compared with patients without a thrombus. When measured over time, antithrombin III remained lower (p = 0.002) and tissue plasminogen activator antigen higher (p = 0.005) in those who developed a thrombus compared with those who did not. There were no other statistically significant differences in biomarkers of coagulation between patients with and without thrombosis. CONCLUSION: One-third of patients undergoing palliative surgery for single ventricle physiology develop thrombosis. Decreased ventricular function, low antithrombin III, and increased tissue plasminogen activator may predict those most suitable for randomized clinical trials of anticoagulation. PMID- 21979274 TI - Pancreatic fat accumulation and its relationship with liver fat content and other fat depots in obese individuals. AB - BACKGROUNDS AND AIMS: We assessed the associations between pancreatic fat accumulation and other fat compartments, including liver fat and visceral adipose tissue as well as insulin resistance and other metabolic abnormalities in obese individuals. SUBJECTS AND METHODS: We studied 42 Caucasian adults with obesity [20 men and 22 women; mean body mass index (BMI) 35.2+/-4 kg/m(2)], who had no history of liver diseases or excessive alcohol consumption, in which subcutaneous, visceral, liver, and pancreatic fat contents were quantified by an in-opposed-phase magnetic resonance imaging (MRI) technique. RESULTS: Compared with patients in the lower tertile (<5.6%, no.=15), those in the upper tertile of liver fat content had more visceral adipose tissue, greater insulin resistance and had higher values of BMI, blood pressure, triglycerides and lower HDL cholesterol and adiponectin. Notably, pancreatic fat accumulation also significantly increased across tertiles of liver fat content. In univariate analysis, the strongest correlates of pancreatic fat were visceral and liver fat contents (r=0.80 and r=0.54, p<0.001- 0.0001, respectively). Pancreatic fat accumulation was also moderately associated with insulin resistance and other metabolic syndrome features. However, when adjusted for age, gender and visceral adipose tissue, the associations of pancreatic fat accumulation with liver fat and other metabolic abnormalities were no longer significant. CONCLUSIONS: There are significant associations between pancreatic fat accumulation and liver fat content as well as insulin resistance and other metabolic abnormalities in obese, but otherwise healthy, individuals. However, these associations are largely mediated by the amount of visceral adipose tissue. PMID- 21979275 TI - Using the T-Coffee package to build multiple sequence alignments of protein, RNA, DNA sequences and 3D structures. AB - T-Coffee (Tree-based consistency objective function for alignment evaluation) is a versatile multiple sequence alignment (MSA) method suitable for aligning most types of biological sequences. The main strength of T-Coffee is its ability to combine third party aligners and to integrate structural (or homology) information when building MSAs. The series of protocols presented here show how the package can be used to multiply align proteins, RNA and DNA sequences. The protein section shows how users can select the most suitable T-Coffee mode for their data set. Detailed protocols include T-Coffee, the default mode, M-Coffee, a meta version able to combine several third party aligners into one, PSI (position-specific iterated)-Coffee, the homology extended mode suitable for remote homologs and Expresso, the structure-based multiple aligner. We then also show how the T-RMSD (tree based on root mean square deviation) option can be used to produce a functionally informative structure-based clustering. RNA alignment procedures are described for using R-Coffee, a mode able to use predicted RNA secondary structures when aligning RNA sequences. DNA alignments are illustrated with Pro-Coffee, a multiple aligner specific of promoter regions. We also present some of the many reformatting utilities bundled with T-Coffee. The package is an open-source freeware available from http://www.tcoffee.org/. PMID- 21979278 TI - Hyponatremia, prevalence, diagnosis, and management. PMID- 21979276 TI - Selective 2'-hydroxyl acylation analyzed by protection from exoribonuclease (RNase-detected SHAPE) for direct analysis of covalent adducts and of nucleotide flexibility in RNA. AB - RNA SHAPE chemistry yields quantitative, single-nucleotide resolution structural information based on the reaction of the 2'-hydroxyl group of conformationally flexible nucleotides with electrophilic SHAPE reagents. However, SHAPE technology has been limited by the requirement that sites of RNA modification be detected by primer extension. Primer extension results in loss of information at both the 5' and 3' ends of an RNA and requires multiple experimental steps. Here we describe RNase-detected SHAPE that uses a processive, 3'->5' exoribonuclease, RNase R, to detect covalent adducts in 5'-end-labeled RNA in a one-tube experiment. RNase R degrades RNA but stops quantitatively three and four nucleotides 3' of a nucleotide containing a covalent adduct at the ribose 2'-hydroxyl or the pairing face of a nucleobase, respectively. We illustrate this technology by characterizing ligand-induced folding for the aptamer domain of the Escherichia coli thiamine pyrophosphate riboswitch RNA. RNase-detected SHAPE is a facile, two day approach that can be used to analyze diverse covalent adducts in any RNA molecule, including short RNAs not amenable to analysis by primer extension and RNAs with functionally important structures at their 5' or 3' ends. PMID- 21979277 TI - Fasting reduces the kiss1 mRNA levels in the caudal hypothalamus of gonadally intact adult female rats. AB - Kisspeptin, which is the product of the kiss1 gene and its receptor kiss1r, have emerged as the essential gatekeepers of reproduction. The present study used gonadally intact female rats to evaluate fasting-induced suppression of the KiSS 1 system of anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) under normal physiological conditions. Starting on the day of estrous, one group of rats was subjected to 72 h of food deprivation, while the other group of rats was able to continue feeding ad libitum. The length of the estrous cycle was significantly longer in the food-deprived rats as compared to the feeding rats. At the end of the 72-h food deprivation period, all of the food-deprived rats were at the diestrous phase, with their serum concentrations of LH and leptin significantly lower than that observed in the feeding rats. In addition, as compared to the feeding rats, the expression levels of kiss1 mRNA were significantly lower in the food-deprived rats in the posterior hypothalamic block, which contained the ARC, but not in the anterior hypothalamic block, which contain the AVPV. However, both the kiss1r mRNA expression levels in the anterior and posterior hypothalamic blocks and the neurokinin B and neurokinin 3 receptor mRNA expression levels in the posterior hypothalamic block were not significantly different between the feeding and food-deprived rats. Thus, lower kiss1 mRNA levels in the ARC appear to be responsible for the fasting-induced inhibition of gonadotrophin secretion and subsequent prolongation of the estrous cycle. PMID- 21979279 TI - The role of ACE gene polymorphism on pathogenesis of ischemic stroke. AB - AIM: to describe the role of ACE gene polymorphism on pathogenesis of ischemic stroke in patients with the history of hypertension. The study was conducted in a population of Palembang city. METHODS: approximately 3 ml of peripheral blood samples were obtained by using venipuncture on antecubital vein. The samples were collected in tubes that contained ethylene diamine tetraacetic acid (EDTA) for DNA analysis. The DNA was extracted from leukocytes according to the standard DNAzol(r) Extraction Protocol. Samples were stored at -80 degrees C until the analysis. Template DNA was then amplified by using a pair of sense oligonucleotide primer of 5'-CTGG AGACC ACTCCCATCCTTTCT-3' and antisense primer 5'-GATGGTGGCCATCAC ATTCGTC AGAT-3', 10 pmol of each primer. The PCR mixture contained 20 ng of genomic DNA, 3 mM MgCl2, 50 mM KCl, 10 mM Tris-HCl pH 8.4, 5% dimethyl-sulphoxide (DMSO), each of 0,5 mM deoxyribonucleoside triphosphate (dNTPs) and 1 unit of Taq polymerase in a final volume of 50 MUL. The DNA was amplified by 30 cycles; denaturation at 940C for 1 min, annealing at 580C for 1 min, and extension at 720C for 2 min, followed by a final extension at 720C for 4 min by using PCR Thermal (Icycler, Biorad, USA). PCR products were separated by electrophoresis on a 2% agarosa gel, and identified by ethidium bromide (0.1%) staining, and finally visualized by ultraviolet light. They were documented by using the geldoc (Biorad, USA). The PCR product is a 190 bp fragment in the absence of insertion (D) and a 490 bp fragment in the presence of insertion (I). RESULTS: ischemic stroke with hypertension or with the history of hypertension was found more frequently in male (70%) and >= 55 year old subjects (60.0%). The study showed that the frequency of II genotype was higher than DI and DD. Moreover, the frequency of I allele was higher than D allele. In healthy normotensive group, the results remained the same. However, different results were found in infarct-stroke group with hypertension history in which the frequency of DI genotype was higher than in II genotype and the DD. The study showed that there was no significant correlation (p=0.188) between ACE gene polymorphism and infarct stroke in subjects with the history of hypertension. ACE gene just has approximately 5% role in developing ischemic stroke. CONCLUSION: there is no significant correlation between ACE gene polymorphism and the development of ischemic stroke in patients with history of hypertension of the population in Palembang. However, the study showed that there is a different pattern of genetic control on ACE compared to previous studies ever done in Caucasians. PMID- 21979280 TI - The risk of hyponatremia in the elderly compared with younger in the hospital inpatient and outpatient. AB - AIM: to comparise the prevalences of hyponatremia between elderly and younger patients in hospital inpatients and outpatients setting. METHODS: this study was done using cross-sectional design. Medical records of all adult patients (age of more than 13 years) from March 2008 to March 2009 in Siloam Hospital Lippo Village whose sodium plasma level data were recorded. The patients were divided into two main groups according to their age, that were elderly and younger. These two main groups were then divided into 4 sub-groups that were general inpatient, special inpatient, general outpatient, and emergency outpatient. The prevalence ratio of the proportion of hyponatremia between the elderly and the younger in the four sub-groups were then analyzed. Independency between the 4 sub-groups and frequency of hyponatremia in each of the two main group were tested by Chi-Square test, using SPSS statistics version 17. RESULTS: in the general inpatient, the prevalence of hyponatremia in the elderly group and the young group were 26.32% and 10.85% respectively, with the Prevalence Ratio of 2,43 (95% CI, 0,11-0,19). In the general outpatient, the prevalence of hyponatremia in the elderly group and the young group were 7.18% and 2.98% respectively, with the Prevalence Ratio of 2,40 (95% CI, 0,02-0,06). In the emergency outpatient, the prevalence of hyponatremia in the elderly group and the young group were 18.28% and 7.71% respectively, with the Prevalence Ratio of 2,37 (95% CI, 0,08-0,14). In the special inpatient, the prevalence of hyponatremia in the elderly group and the young group were 14.98% and 5.58% respectively, with the Prevalence Ratio of 2,69 (95% CI, 0,05-0,13). The risk to get hyponatremia during inpatient was significantly higher in the elderly with the Prevalence Ratio of 2.79 (95% CI, 0,03-0,07). Chi Square analysis which was done in both the elderly and the younger group revealed that the place of the services will influence the frequency of hyponatremia significantly (p = 0.000). CONCLUSION: compared with the younger group, the mean of the risk for the elderly group to get hyponatremia in the hospital inpatient and outpatient is 2.54 times higher. PMID- 21979281 TI - Correlation between clinical stage of solid tumor and D dimer as a marker of coagulation activation. AB - AIM: to examine the relationship between clinical stage of solid cancers and plasma D dimer value. METHODS: patients with solid cancer treated in Sanglah hospital who met study ctiteria were consecutively recruited and studied in order to examine the relationship between clinical stage of solid cancers and plasma D dimer value. Plasma D dimer was measured by ELISA (Nycocard) and TNM system to assign each patient into stage I,II,III and IV according to American Joint Committee on Cancer. Rank Spearman analysis was used to determine the relationship and one way Anova to compare the mean difference of D dimer between group of clinical stages. RESULTS: there were 79 patients included, mostly female (72,2%) and 57% was in age group of 40-59 years old. Level of D dimer >500 ng/ml were found in 60 patients and 19 patients with D dimer <500 ng/ml. The most frequent cancer was cervix (32.9%) then followed by nasopharyng cancer (16.5%). Clinical stage I,II,III, and IV were 6.3%, 16.5%, 53.2% and 24.1% respectively. Thrombocytosis (>400.103/uL) was found 50.6% as well as leukocytosis 62%. Although the differences of mean D dimer in each type of solid cancers were big enough but it was not statistically significant (p = 0.156). Plasma D dimer was positively correlated with clinical stage of solid cancers (r = 0.367; p = 0.001). CONCLUSION: plasma D dimer level was positively correlated with clinical stage of solid cancers. High plasma D dimer could be a marker for advanced stage of a patient with solid cancer. PMID- 21979282 TI - Bone marrow-derived stem cells as an adjunctive treatment for acute myocardial infarction: a systematic review and meta-analysis. AB - AIM: to confirm the beneficial effect of BMCs therapy over placebo in AMI patients with inclusion only to the randomized double blind placebo-controlled trials. METHODS: we searched multiple database (MEDLINE, CENTRAL, CINAHL) through January 2011 for randomized, double-blind, placebo-controlled trials evaluating the efficacy and safety of BMCs for the treatment of AMI. We subsequently performed a random-effect meta-analysis to assess the eligible studies included related to the primary outcomes (mean LVEF, LVESV, and LVEDV changes from baseline) and secondary outcomes (all-cause mortality, recurrent MI, rehospitalization for HF). RESULTS: ten RCTs (total=906 patients) were included. BMCs therapy was proven superior to placebo regarding mean LVEF change (2.07%; 95% CI, 0.55% to 3.59%; [I2=57%; p=0.008]), LVESV (5.52 mL; 95% CI, -7.68 mL to 3.36 mL; [I2=16%; p<0.00001]), and LVEDV (3.08 mL; 95% CI, -5.57 mL to -0.58 mL; [I2=23%, p=0.02]) from baseline. BMCs therapy showed no difference with regards to mortality events when compared to placebo (OR 1.01; 95% CI, 0.35 to 2.94; [I2=0%; p=0.98]), but exerts protective effects toward recurrent MI (OR 0.45; 95% CI, 0.09 to 2.16; [I2=8%; p=0.32]) and rehospitalization for HF (OR 0.39; 95% CI, 0.08 to 1.85; [I2=0%; p=0.24]). All outcomes were sustained for a long period of time (up to 5 years). CONCLUSION: the resulting meta-analysis concluded that BMCs therapy consistently improves cardiac performance parameters (LVEF, LVESV, and LVEDV) when compared to placebo, even after the establishment of primary intervention. It is also safe to use and prevents the development of recurrent MI and HF. PMID- 21979283 TI - Isolation and cultivation of mesenchymal stem cells from iliac crest bone marrow for further cartilage defect management. AB - AIM: to validate isolation and cultivation methods of bone marrow mesenchymal stem cells (BM-MSCs) from iliac crest, and to compare biological characteristics of BM-MSCs from different age groups for preparation of autologous stem cell therapy in cartilage defect. METHODS: patients undergoing spinal surgery were selected and grouped according to age. Iliac crest bone marrow from the patients was aspirated. BM-MSCs were isolated from the bone marrow and then cultivated. Their biological characteristics including morphological appearances and surface biomarkers were evaluated. Growth curves were observed. Sterility and Mycoplasma tests were also performed for quality assessment of BM-MSCs culture procedure. RESULTS: in average, cultivated-BM-MSCs reached the number of 7.56-22.95 x 106 in 4-7 weeks period. BM-MSCs of all age groups showed the same quality of morphology, shape and surface biomarkers (CD105+, CD73+, CD34-, CD45-, CD14-, CD19-, HLA-DR-). CONCLUSION: our procedures in isolating and cultivating of BM MSCs have reached required amount for implantation into the cartilage lesion. In addition, the cultivated-BM-MSCs' biological characteristics were also in accordance with International Society of Cell Therapy (ISCT) MSCs criteria. PMID- 21979284 TI - The efficacy of Bacillus Calmette-Guerin vaccinations for the prevention of acute upper respiratory tract infection in the elderly. AB - AIM: to study the efficacy of BCG vaccinations, once a month for 3 consecutive months, in elderly on the prevention of acute upper respiratory tract infection (AURTI), interferon - gamma (IFN-gamma) and interleukin (IL)-10 level in the BCG and placebo group and their comparison in the period of the study. METHODS: an original, experimental, prospective study with randomly pre-test and post-test design. Subjects were 60-75 years old, divided into BCG and placebo groups. The subjects in the BCG group received BCG vaccination, meanwhile the subjects in the placebo group received solvent for BCG vaccine, once a month for 3 months in succession at the deltoid region for each group. The subjects in both groups were evaluated every 2 weeks for the infiltrate diameter, on the 8th and 12th week for the scar measurements, and every 4 weeks for the prevalence of AURTI. The levels of IFN-gamma and IL-10 were done at the initial and the end of the study. Data obtained were the prevalence of AURTI, the infiltrate and scar diameters at the site of BCG vaccination, and the levels of IFN-gamma and IL-10. Data collected from January 2010 to June 2010 (6 months) at Internal Medicine Policlinics, Prof.Dr.RD Kandou General Hospital, Manado, North Sulawesi, Indonesia. Statistical analysis was performed using descriptive subject's characteristics, paired and unpaired T test and non-parametric test (Mann-Whitney and Wilcoxon test), and Spearman non-parametric test. RESULTS: in comparison between two groups in the period of the study, we found a significant reduction in the BCG group on the prevalence of AURTI and significant increase of IFN-gamma level in BCG group compared to the placebo group. There were significant increase of IFN gamma and IL-10 levels in the BCG group compared to the placebo group. There were insignificant increase of IFN-gamma and IL-10 levels in the pre- and post-BCG group. The increase of IFN-gamma level was positively significant correlated with the increase of the infiltrate and scar diameters in the BCG group. CONCLUSION: BCG vaccinations in elderly, once a month for 3 consecutive months, significantly prevent the AURTI and can increase the IFN-gamma level as Th1 response and IL-10 as Treg response in the period of the study. PMID- 21979285 TI - Gastrointestinal strongyloidiasis in immunocompromised patients: a case report. AB - Strongyloides stercoralis is an intestinal nematode, endemic in tropical countries. The parasite has a complex life cycle, causing a long-lived auto infection in hosts. It may remain asymptomatic or with minor symptoms; the dormant carrier state of the illness may persist for a long period of time. Inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC), commonly treated with immunosuppressive drugs is a well-known condition predisposing individuals to various infections. The condition is more prevalent among immunocompromised patients; the diagnosis of which, however, is troublesome in such individuals. The present article reports a 45- year-old female with gastric strongyloides stercoralis infection while receiving the treatment for her underlying UC. Strongyloides stercoralis can easily be missed especially in IBD patients in the absence of accompanying diarrhea or any symptom of lower GI discomfort because it presents with various manifestations including multiple GI symptoms, multiple stool exams and special attention to peripheral eosinophilia are specially important but not so sensitive or specific. PMID- 21979286 TI - Management of chronic constipation in the elderly. AB - Constipation is a common complaint among the elderly. Constipation can be defined as the passage of small hard stool infrequently and with difficulty. Definitions of constipation vary widely, and therefore Rome III criteria was recommended to be used in defining constipation. Constipation in the elderly is not simply related to the aging. It is a major feature of disorders of colorectal motility. The symptom of constipation could also arise secondary to other conditions. The management of chronic constipation in the elderly should include a detailed medical history and physical examination to exclude secondary causes for constipation. Laboratory evaluation should be performed in the initial assessment of the patient. If the initial investigations are normal, empiric therapy should be initiated. Patients not responding to the initial therapy are considered to have refractory constipation. Thus, diagnostic tests need to be performed in these patients. Further management such as newer medications, biofeedback and surgery might provide new hope to patients with refractory constipation. This review article focuses on the approach and treatment of chronic constipation in the elderly. PMID- 21979287 TI - Retroperitoneal benign mature teratoma. PMID- 21979288 TI - Therapeutic drug monitoring: focus on conditions in Indonesia. AB - It has been long recognized that large inter-individual variability is commonly observed in response to drug administration. The large response variability of certain drugs with narrow margin of safety may induce toxicity. To avoid this and to optimize the result of drug treatment, therapeutic drug monitoring (TDM) service has been routinely applied in hospitals in well-developed countries. For certain drugs, the TDM service has been shown beneficial and cost-effective. In Indonesia, the TDM has not yet been implemented. There are three problems that hamper the implementation of TDM here, i.e. cost, the limited expertise to provide interpretation for result of drug assay, and the lack of communication with the clinicians. Today the patient safety issue is considered of paramount importance in the health care service in all hospitals. Therefore, it is now the time to commence the TDM service in Indonesia. This can be started with a pilot project in a large hospital, followed by the others. To avoid unnecesary wasting of funds, TDM should be limited for drugs which toxicity is not readily observed clinically. PMID- 21979289 TI - Diagnosis and treatment update: cholangiocarcinoma. AB - Cholangiocarcinoma is a rare and very aggressive neoplasm that arises from the biliary epithelium, constitutes approximately 2% of all reported cancer, and accounts for about 3% of all gastrointestinal malignancies. Up to date, there are many modalities to diagnosis and treat with a range of sensitivity and specificity, and also the advantage and disadvantage of its modality. As a physician, we should be able to assess and choose promptly which modality is best for our patient, even for paliative care. Treatment modalities are surgery and non-surgery like adjuvant chemotherapy, radiation, chemoradiation, radiotherapy, TACE, 5-FU chemoinfusion, intralesion PEI, photodynamic therapy, liver transplantation, and paliative therapy. The choice of treatment varies individually. Radical surgery remains the optimal therapy and offering a potential for cure. Overall prognosis in these patients is poor and survival is limited to a few months. PMID- 21979290 TI - Efficacy and safety of right hemihepatectomy through the right retrohepatic tunnel. AB - We wished to study the efficacy and safety of the retrograde ligation of short hepatic veins (SHVs) and the right hepatic vein (HV) through the retrohepatic tunnel in patients who underwent hemihepatectomy due to large hepatic carcinoma in the right lobe of the liver. Right hemihepatectomy was performed in 23 patients with tumors larger than 8 cm in diameter. The liver was separated at the secondary porta, and the interspace between right HVs and middle HVs was expanded. The right hepatic portal vein and hepatic artery were freed and ligated, followed by the retrograde dissection of SHVs and the right HV along the right retrohepatic space anterior to the inferior vena cava. A blocking belt was set at the left side of the midline, after which the right liver was cut off. The procedure was successfully completed in all patients. The average amount of intraoperative blood loss was 640 ml. The change in hepatic function was observed on the third postoperative day. Twenty-two patients exhibited satisfactory results; one patient died from postoperative hepatic failure. In conclusion, this procedure can be safely performed in most hemihepatectomy patients with liver tumors. PMID- 21979291 TI - False normal von Willebrand factor activity by monoclonal antibody-based ELISA in a patient with type 2A(IID) von Willebrand disease. PMID- 21979292 TI - San-Huang-Xie-Xin-Tang protects cardiomyocytes against hypoxia/reoxygenation injury via inhibition of oxidative stress-induced apoptosis. AB - Oxidative stress has been widely implicated in the pathogenesis of hypoxia/reoxygenation (H/R) injury. San-Huang-Xie-Xin-Tang (SHXT), a widely used traditional Chinese medication, has been shown to possess antioxidant effects. Here, we investigated whether SHXT and its main component baicalin can attenuate oxidative stress induced by H/R injury. H9c2 rat ventricular cells were exposed to SHXT or baicalin followed by hypoxia for 24 h and/or reoxygenation for 8 h. Pretreatment with SHXT and baicalin both significantly prevented cell death and production of reactive oxygen species induced by hypoxia or H/R in H9c2 cardiomyoctes. In addition, SHXT and baicalin also inhibited hypoxia- or H/R induced apoptosis, with associated decreased Bax protein, increased Bcl-2 protein, and decreased caspase-3 activity. Furthermore, we found that hypoxia and H/R decreased endothelial nitric oxide synthase (eNOS) expression and nitrite production, and these effects were counteracted by SHXT and baicalein. Finally, SHXT inhibited H/R-induced activation of p38 mitogen activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation in H9c2 rat ventricular cells. The present study demonstrates for the first time that SHXT can protect cardiomyocytes from H/R injury via inhibition of oxidative stress-induced apoptosis. These cardioprotective effects are possibly mediated through eNOS enhancement and p38 MAPK and JNK-dependent signaling pathways. PMID- 21979293 TI - Features of mobile diabetes applications: review of the literature and analysis of current applications compared against evidence-based guidelines. AB - BACKGROUND: Interest in mobile health (mHealth) applications for self-management of diabetes is growing. In July 2009, we found 60 diabetes applications on iTunes for iPhone; by February 2011 the number had increased by more than 400% to 260. Other mobile platforms reflect a similar trend. Despite the growth, research on both the design and the use of diabetes mHealth applications is scarce. Furthermore, the potential influence of social media on diabetes mHealth applications is largely unexplored. OBJECTIVE: Our objective was to study the salient features of mobile applications for diabetes care, in contrast to clinical guideline recommendations for diabetes self-management. These clinical guidelines are published by health authorities or associations such as the National Institute for Health and Clinical Excellence in the United Kingdom and the American Diabetes Association. METHODS: We searched online vendor markets (online stores for Apple iPhone, Google Android, BlackBerry, and Nokia Symbian), journal databases, and gray literature related to diabetes mobile applications. We included applications that featured a component for self-monitoring of blood glucose and excluded applications without English-language user interfaces, as well as those intended exclusively for health care professionals. We surveyed the following features: (1) self-monitoring: (1.1) blood glucose, (1.2) weight, (1.3) physical activity, (1.4) diet, (1.5) insulin and medication, and (1.6) blood pressure, (2) education, (3) disease-related alerts and reminders, (4) integration of social media functions, (5) disease-related data export and communication, and (6) synchronization with personal health record (PHR) systems or patient portals. We then contrasted the prevalence of these features with guideline recommendations. RESULTS: The search resulted in 973 matches, of which 137 met the selection criteria. The four most prevalent features of the applications available on the online markets (n = 101) were (1) insulin and medication recording, 63 (62%), (2) data export and communication, 61 (60%), (3) diet recording, 47 (47%), and (4) weight management, 43 (43%). From the literature search (n = 26), the most prevalent features were (1) PHR or Web server synchronization, 18 (69%), (2) insulin and medication recording, 17 (65%), (3) diet recording, 17 (65%), and (4) data export and communication, 16 (62%). Interestingly, although clinical guidelines widely refer to the importance of education, this is missing from the top functionalities in both cases. CONCLUSIONS: While a wide selection of mobile applications seems to be available for people with diabetes, this study shows there are obvious gaps between the evidence-based recommendations and the functionality used in study interventions or found in online markets. Current results confirm personalized education as an underrepresented feature in diabetes mobile applications. We found no studies evaluating social media concepts in diabetes self-management on mobile devices, and its potential remains largely unexplored. PMID- 21979294 TI - Soft plasma processing of organic nanowires: a route for the fabrication of 1D organic heterostructures and the template synthesis of inorganic 1D nanostructures. AB - Hierarchical (branched) and hybrid metal-NPs/organic supported NWs are fabricated through controlled plasma processing of metalloporphyrin, metallophthalocyanine and perylene nanowires. The procedure is also applied for the development of a general template route for the synthesis of supported metal and metal oxide nanowires. PMID- 21979295 TI - Binary and ternary uranium(VI) humate complexes studied by attenuated total reflection Fourier-transform infrared spectroscopy. AB - The complexation of U(VI) with humic acid (HA) in aqueous solution has been investigated at an ionic strength of 0.1 M (NaCl) in the pH range between pH 2 and 10 at different carbonate concentrations by attenuated total reflection Fourier-transform infrared (ATR FT-IR) spectroscopy. For the first time, the formation of binary and ternary U(VI) humate complexes was directly verified by in situ spectroscopic measurements. The complex formation constants for the binary U(VI) humate complex (UO(2)HA(II)) and for the ternary U(VI) mono hydroxo humate complex (UO(2)(OH)HA(I)) as well as the ternary U(VI) dicarbonato humate complex (UO(2)(CO(3))(2)HA(II)(4-)) determined from the spectroscopic data amount to log beta(0.1 M) = 6.70 +/- 0.25, log beta(0.1 M) = 15.14 +/- 0.25 and log beta(0.1 M) = 24.47 +/- 0.70, respectively, and verify literature data. PMID- 21979296 TI - Long-term antiepileptic treatment with histone deacetylase inhibitors may reduce the risk of prostate cancer. AB - Various antiepileptic drugs such as valproic acid, carbamazepine, oxcarbazepine, lamotrigine and levetiracetam are known to exert histone deacetylase inhibitory (HDACi) properties, which can modify aberrantly silenced gene expression by an epigenetic mechanism. This study was initiated to examine a potential beneficial effect of these drugs on prostate cancer (PC) development. The prostate-specific antigen (PSA) levels of 106 patients under long-term treatment with antiepileptic drugs and known HDACi properties were examined. PSA represents a hallmark in the early detection of PC, and its levels may predict an invasive disease in subsequent years. For in-vitro experiments, the PC cell line LNCaP was treated with HDACi drugs; subsequently, PSA and further PC markers were assessed. When men over 50 years of age were treated with HDACi drugs they had lower age corrected PSA levels compared with control groups, according to the following ranking: valproic acid>levetiracetam>carbamazepine/oxcarbazepine>lamotrigine. Furthermore, there was a correlation between PSA reduction and the number of HDACi drugs within the medication, lending credence to the idea that a synergistic effect might be possible. Moreover, in vitro, HDACi drugs decrease PSA on mRNA and protein levels and exhibit further oncoprotective properties.The fact that HDACi drugs exert antiproliferative effects on neoplastic cells in vitro and in vivo, which are paralleled by expression alterations of aberrantly regulated genes, underlines the potential therapeutic value of HDACi drugs. These data suggest that long-term HDACi treatment can positively influence the characteristically slow transformation of tumour precursor cells in the prostate and may thus reduce a patient's risk of developing PC. PMID- 21979297 TI - Epigenetic regulation of death-associated protein kinase expression in primary gastric cancers from Chinese patients. AB - Death-associated protein kinase (DAPK) is a novel serine/threonine kinase involved in apoptosis and tumor suppression. Promoter methylation is an important mechanism by which tumor suppressor gene transcription is repressed in cancer cells. Although reduced expression and aberrant methylation of DAPK has been reported in various human cancers, including gastric cancer (GC), the results remain discrepant. We aimed to investigate DAPK mRNA and protein expression in primary GC tissues from Chinese patients and establish a possible relationship between the promoter methylation status and the decreased expression of DAPK. The mRNA level, protein expression, and promoter methylation of DAPK were examined, in the cancer tissues and the corresponding, adjacent nontumor tissues of the 62 GC cases, by RT-PCR, western blotting and methylation-specific PCR, respectively. DAPK mRNA and protein expression in GC tissues was significantly reduced compared with corresponding nontumor tissues (P<0.0001). The methylation frequency of the DAPK promoter in primary GC tissues is significantly higher than in the corresponding nontumor tissues (54.8 vs. 17.7%, P<0.0001). Furthermore, DAPK mRNA expression in tissues containing aberrant promoter methylation was significantly reduced compared with GC tissues with unmethylated DAPK promoter (P<0.0001). Moreover, a significant correlation was demonstrated between the TNM stage and the degree of DAPK promoter methylation in primary GCs (P=0.04). DAPK protein and mRNA expression was reduced in GC tissues of Chinese patients. Diminished expression of DAPK was associated with promoter methylation. PMID- 21979298 TI - The modulation of catecholamines to the immune response against bacteria Vibrio anguillarum challenge in scallop Chlamys farreri. AB - Catecholamines are pivotal signal molecules in the neuroendocrine-immune regulatory network, and implicated in the modulation of immune response. In the present study, the activities of some immune-related enzymes and the concentration of catecholamines were determined in circulating haemolymph of scallops Chlamys farreri after bacteria Vibrio anguillarum challenge. The activities of superoxide dismutase (SOD), catalase (CAT) and lysozyme (LYZ) increased significantly and reached 610 U mg(-1) at 12 h, 37.6 U mg(-1) at 6 h and 261.5 U mg(-1) at 6 h after bacteria challenge, respectively. The concentration of norepinephrine, epinephrine and dopamine also increased significantly and reached 114.9 ng mL(-1) at 12 h, 86.9 ng mL(-1) at 24 h and 480.4 pg mL(-1) at 12 h after bacteria challenge, respectively. Meanwhile, the activities of these immune-related enzymes in haemolymph were monitored in those scallops which were challenged by bacteria V. anguillarum and stimulated simultaneously with norepinephrine, epinephrine and adrenoceptor antagonist. The injection of norepinephrine and epinephrine repressed significantly the induction of bacteria challenge on the activities of immune-related enzymes, and they were reduced to about half of that in the control groups. The blocking of alpha and beta-adrenoceptor by antagonist only repressed the increase of CAT and LYZ activities significantly, while no significant effect was observed on the increase of SOD activities. The collective results indicated that scallop catecholaminergic neuroendocrine system could be activated by bacteria challenge to release catecholamines after the immune response had been triggered, and the immune response against bacteria challenge could been negatively modulated by norepinephrine, epinephrine, and adrenoceptor antagonist. This information is helpful to further understand the immunomodulation of catecholamines in scallops. PMID- 21979299 TI - Expression of VASA mRNA in testis as a significant predictor of sperm recovery by microdissection testicular sperm extraction in patient with nonobstructive azoospermia. AB - It would be of value to evaluate whether expression levels of mRNAs playing important roles in spermatogenesis could be used as predictors of successful testicular sperm recovery by microdissection testicular sperm extraction (TESE) in patients with nonobstructive azoospermia (NOA). This study included 52 patients with NOA who underwent therapeutic sperm retrieval by micro-TESE at our institution. We measured expression levels of VASA, outer dense fiber-1 (ODF1), ODF2, and sperm mitochondria-associated cysteine-rich protein (SMCP) mRNAs in testicular tissue specimens obtained from these patients by quantitative real time reverse transcription polymerase chain reaction. Expression patterns of these mRNAs were analyzed focusing on the outcomes of sperm retrieval by micro TESE. There were no significant differences in age, testicular volume, and serum levels of follicle-stimulating hormone, luteinizing hormone, and testosterone between successful and unsuccessful TESE groups; however, the proportion of patients with Sertoli cell only in the successful TESE group was significantly lower than that in the unsuccessful TESE group. Additionally, expression levels of VASA, ODF1, ODF2, and SMCP mRNAs in the successful TESE group were significantly greater than those in the unsuccessful TESE group. Univariate analysis identified histological classification, VASA, ODF1, ODF2, and SMCP expressions as significant predictors of sperm retrieval, of which only VASA mRNA expression appeared to be independently related to micro-TESE outcome on multivariate analysis. These findings suggest that measurement of VASA mRNA in testis could be a useful adjunct to conventional parameters for predicting sperm retrieval by micro-TESE in patients with NOA. PMID- 21979300 TI - Sibutramine for the treatment of recurrent high-flow priapism. AB - High-flow priapism most often occurs following perineal and penile trauma. We report the case of a 29-year-old man who presented with recurrent priapism and was initially treated with corporal aspiration and intracavernosal injections on multiple emergency department visits and then condition-controlled with sibutramine while on treatment for weight loss. His condition relapsed after the medication was withdrawn from the market, necessitating medical intervention. PMID- 21979301 TI - Semen quality in patients with Chlamydia trachomatis genital infection treated concurrently with prulifloxacin and a phytotherapeutic agent. AB - Chronic prostatitis (CP) due to Chlamydia trachomatis (Ct) infection has a significant impact on young male fertility, and eradication of Ct infection after antibiotic therapy does not always result in recovery of semen quality. The study aim was to evaluate the effects on fertility parameters of L-arginine, L carnitine, acetyl-L-carnitine, and ginseng extracts (FERTIMEV) associated with prulifloxacin in patients affected by CP and oligoasthenoteratozoospermia due to Ct infection. Two hundred and six patients with proven Ct genital infection and oligoasthenoteratozoospermia were enrolled in a prospective, randomized, and controlled study. Prulifloxacin (600 mg) was administered daily for 14 days, and patients were divided into 2 groups: group A: antibiotic therapy alone; and group B: antibiotic therapy and additional therapy with FERTIMEV (1 vial daily for 6 months). Microbiological and semen parameter analyses were performed both at enrollment and after 6 months. National Institutes of Health Chronic Prostatitis Symptom Index and International Prostatic Symptom Score questionnaires were applied. Of the 206 patients, 109 were assigned to group A and 97 to group B. At the enrollment time, no differences were reported with regard to clinical, instrumental, and laboratory data. Six months after treatment, statistically significant differences were demonstrated between both groups in terms of sperm concentration (21.3 +/- 13.2 millions/mL vs 11.5 +/- 13.2 millions/mL) (Cohen's d = 0.61) (P < .001, df = 2, F = 62.10) and percentage of motile sperm (42.4% +/- 5.2% vs 29.3% +/- 11.0%) (Cohen's d = 1.52) (P < .001, df = 2, F = 91.48). In this study treatment with FERTIMEV together with prulifloxacin improved semen parameters in patients with Ct genital infection and oligoasthenoteratozoospermia compared to treatment with prulifloxacin therapy alone. PMID- 21979302 TI - A novel testosterone 2% gel for the treatment of hypogonadal males. AB - Testosterone replacement therapy (TRT) can improve the symptoms, signs, and well being of hypogonadal men by restoring serum testosterone concentrations to physiologic levels. This multicenter, open-label noncomparative trial of men with hypogonadism evaluated the pharmacokinetic profile and safety of a novel testosterone 2% gel (FortestaTM Gel), administered once daily to the front and inner thighs at starting doses of 40 mg/d. The metered-dose delivery system allowed dose adjustments in 10-mg increments between 10 and 70 mg/d. Of the 149 patients enrolled, 138 patients (92.6%) completed the study and 129 patients (86.6%) were included in the efficacy analysis. On day 90, mean testosterone concentration (C(avg) [0-24 hours] +/- SD) was 438.6 +/- 162.5 ng/dL. Overall, 100 (77.5%) patients achieved serum total testosterone concentrations within the normal physiologic range (>= 300 and <= 1140 ng/dL). On day 90, mean testosterone C(max) (+/- SD) was 827.6 +/- 356.5 ng/dL. On day 90, a total of 122 patients (94.6%) had C(max) levels of 1500 ng/dL or less and 2 patients (1.6%) had values between 1800 and 2500 ng/dL. Similar results for C(avg) (0-24 hours) and C(max) were observed on day 35. All enrolled patients were included in the safety analysis. Testosterone 2% gel was generally well tolerated, with the most common adverse events (AE) being mild and moderate skin reactions. There were no serious AEs related to testosterone 2% gel. Once-daily testosterone 2% gel restored levels of testosterone in more than 75% of patients, with low risk of supraphysiologic testosterone levels. Patients may find this a suitable option for TRT because of its application site and low volume. PMID- 21979303 TI - Articular cartilage of the posterior condyle can affect rotational alignment in total knee arthroplasty. AB - PURPOSE: Rotational alignment is important for patellar tracking, ligament balance, and tibiofemoral congruity after total knee arthroplasty (TKA). The posterior condylar axis is often referred to as a rotational alignment landmark. However, articular cartilage wear localized only in the medial condyle might affect the accuracy of rotation, because surgical planning based on CT does not consider the cartilage thickness. The purpose of this study was to clarify whether the cartilage thickness of the posterior condyle affects rotational alignment after TKA. METHODS: A total of 40 osteoarthritis patients waiting for TKA were recruited. MRI of axial sections was performed preoperatively. Scans were controlled to make the cross section perpendicular to the mechanical axis of the femur on the coronal plane and to the tangent line of the distal femur on the sagittal plane, so that the surgical section of the actual femur could be simulated. The condylar twist angle (CTA) was measured with and without articular cartilage. The cartilage thickness on the medial and lateral posterior condyles was surveyed in both MRI images and surgical specimens. RESULTS: The CTA without cartilage (6.8 +/- 2.0 degrees ) was significantly larger than the CTA with cartilage (5.2 +/- 2.0 degrees ) (P < 0.01), and 12 knees (30%) demonstrated differences of more than 2 degrees. The cartilage depicted in MRI showed almost the same thickness as the actual specimens and was significantly thicker on the lateral condyles. CONCLUSIONS: Surgical planning for TKA not considering articular cartilage might lead to the externally rotated malposition of the femoral implant. LEVEL OF EVIDENCE: II. PMID- 21979304 TI - Purification and partial characterization of glutathione S-transferases from three field populations of Panonychus citri (Acari: Tetranychidae). AB - Glutathione S-transferases (GSTs) play central roles in phase II detoxification of both xenobiotics (drugs, insecticides, and herbicides) and endogenous compounds in almost all living organisms. In this study, we successfully purified the GSTs from the citrus red mite, Panonychus citri, by affinity chromatography on Glutathione Sepharose 4B and compared the biochemical characterizations of the purified GSTs from three field populations [beibei (BB), wanzhou (WZ), and zhongxian (ZX)]. SDS-PAGE revealed that the molecular weight of GSTs from three populations consisted of two subunits of 27.3 and 26.1 kDa. The specific activity of the purified GSTs from the WZ and ZX populations was increased 1.5- and 3.8 fold, respectively, compared with the BB population. Accordingly, the pyridaben susceptibility of WZ and ZX populations was less compared with BB population. Kinetic analyses showed that the WZ and ZX populations had higher substrate specificity compared with the BB population based on the values of k (cat) and k (cat) /K (m) to both reduced glutathione (GSH) and 1-chloro-2,4-dinitrobenzene (CDNB). The in vitro inhibition studies of GSTs indicated that the I (50) values of pyridaben from WZ and ZX populations of P. citri expressed 1.6- and 4.4-fold decreases, respectively, compared to the I (50) value of pyridaben from the BB population. In conclusion, all evidence suggested that the purified GSTs may partially contribute to the susceptibility of acaricide pyridaben in field populations of P. citri. PMID- 21979305 TI - Gene expression: Variety is the splice of strife. PMID- 21979306 TI - Tumour suppressors: HOTS makes antisense. PMID- 21979308 TI - Pancreatic cancer: Fibroblast co-conspirators. PMID- 21979307 TI - TRIM proteins and cancer. AB - Emerging clinical evidence shows that the deregulation of ubiquitin-mediated degradation of oncogene products or tumour suppressors is likely to be involved in the aetiology of carcinomas and leukaemias. Recent studies have indicated that some members of the tripartite motif (TRIM) proteins (one of the subfamilies of the RING type E3 ubiquitin ligases) function as important regulators for carcinogenesis. This Review focuses on TRIM proteins that are involved in tumour development and progression. PMID- 21979309 TI - Salicylic acid and calcium-induced protection of wheat against salinity. AB - Soil salinity is one of the important environmental factors that produce serious agricultural problems. The objective of the present study was to determine the interactive effect of salicylic acid (SA) and calcium (Ca) on plant growth, photosynthetic pigments, proline (Pro) concentration, carbonic anhydrase (CA) activity and activities of antioxidant enzymes of Triticum aestivum L. (cv. Samma) under salt stress. Application of 90 mM of NaCl reduced plant growth (plant height, fresh weight (FW) and dry weight (DW), chlorophyll (Chl) a, Chl b, CA activity) and enhanced malondialdehyde (MDA) and Pro concentration. However, the application of SA or Ca alone as well as in combination markedly improved plant growth, photosynthetic pigments, Pro concentration, CA activity and activities of antioxidant enzymes peroxidase (POD), catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR) and ascorbate peroxidase (APX) under salt stress. It was, therefore, concluded that application of SA and Ca alone as well as in combination ameliorated the adverse effect of salinity, while combined application proved more effective to reduce the oxidative stress generated by NaCl through reduced MDA accumulation, Chl a/b ratio and Chls degradation and enhanced activities of antioxidant enzymes. PMID- 21979310 TI - Plasmolysis effects and osmotic potential of two phylogenetically distinct alpine strains of Klebsormidium (Streptophyta). AB - The osmotic potential and effects of plasmolysis were investigated in two different Klebsormidium strains from alpine habitats by incubation in 300-2,000 (3,000) mM sorbitol. Several members of this genus were previously found to tolerate desiccation in the vegetative state yet information was lacking on the osmotic potentials of these algae. The strains were morphologically determined as Klebsormidium crenulatum and Klebsormidium nitens. These species belong to distinct clades, as verified by phylogenetic analysis of the rbcL gene. K. crenulatum is part of to the K. crenulatum/mucosum ('F' clade) and K. nitens of the 'E2' clade. Plasmolysis occurred in K. crenulatum at 800 mM sorbitol (961 mOsmol kg(-1), Psi = -2.09 MPa) and in K. nitens at 600 mM sorbitol (720 mOsmol kg(-1), Psi = -1.67 MPa). These are extraordinarily high osmotic values (very negative osmotic potentials) compared with values reported for other green algae. In K. crenulatum, the maximum photosynthetic rate (Pmax) in the light-saturated range was 116 MUmol O(2) h(-1) mg(-1) chl a. Incubation in 1,000 mM sorbitol decreased Pmax to 74.1% of the initial value, whereas 2,000 mM sorbitol (Psi = 5.87 MPa) lead to an almost complete loss of oxygen production. In K. nitens, Pmax was 91 MUmol O(2) h(-1) mg(-1) chl a under control conditions and incubation in 800 mM sorbitol did not decrease Pmax, 2,000 mM sorbitol decreased Pmax only to about 62.6% of the initial value whereas 3,000 mM sorbitol stopped oxygen evolution. This indicated a broader amplitude for photosynthesis in the examined strain of K. nitens. Control samples and samples plasmolysed for 3 h in 800 mM sorbitol (K. nitens), 1,000 mM sorbitol (K. crenulatum), or 2,000 mM sorbitol were investigated by transmission electron microscopy after chemical or high pressure freeze fixation. In cells undergoing plasmolysis the protoplasts were retracted from the cell wall, the cytoplasm appeared dense, vacuoles were small and fragmented, and the cytoplasm was filled with ribosomes. Thin cytoplasmic strands were connected to the cell wall; 2,000 mM sorbitol increased the effect. The content of soluble carbohydrates in these two strains was investigated by HPLC, as this is one known mechanism for cells to maintain high osmotic pressure of the cytosol. Both Klebsormidium species contained diverse soluble carbohydrates, including a dominant mixed peak of unidentified oligosaccharides, and more minor amounts of raffinose, sucrose, glucose, xylose, galactose, mannose, inositol, fructose, glycerol, mannitol, and sorbitol. The total content of soluble carbohydrates was approximately 1.2% of the dry weight, indicating that this is not a major factor contributing to the high osmotic potential in these strains of Klebsormidium. PMID- 21979312 TI - Upper cervical and upper thoracic thrust manipulation versus nonthrust mobilization in patients with mechanical neck pain: a multicenter randomized clinical trial. AB - STUDY DESIGN: Randomized clinical trial. OBJECTIVE: To compare the short-term effects of upper cervical and upper thoracic high-velocity low-amplitude (HVLA) thrust manipulation to nonthrust mobilization in patients with neck pain. BACKGROUND: Although upper cervical and upper thoracic HVLA thrust manipulation and nonthrust mobilization are common interventions for the management of neck pain, no studies have directly compared the effects of both upper cervical and upper thoracic HVLA thrust manipulation to nonthrust mobilization in patients with neck pain. METHODS: Patients completed the Neck Disability Index, the numeric pain rating scale, the flexion-rotation test for measurement of C1-2 passive rotation range of motion, and the craniocervical flexion test for measurement of deep cervical flexor motor performance. Following the baseline evaluation, patients were randomized to receive either HVLA thrust manipulation or nonthrust mobilization to the upper cervical (C1-2) and upper thoracic (T1-2) spines. Patients were reexamined 48-hours after the initial examination and again completed the outcome measures. The effects of treatment on disability, pain, C1 2 passive rotation range of motion, and motor performance of the deep cervical flexors were examined with a 2-by-2 mixed-model analysis of variance (ANOVA). RESULTS: One hundred seven patients satisfied the eligibility criteria, agreed to participate, and were randomized into the HVLA thrust manipulation (n = 56) and nonthrust mobilization (n = 51) groups. The 2-by-2 ANOVA demonstrated that patients with mechanical neck pain who received the combination of upper cervical and upper thoracic HVLA thrust manipulation experienced significantly (P<.001) greater reductions in disability (50.5%) and pain (58.5%) than those of the nonthrust mobilization group (12.8% and 12.6%, respectively) following treatment. In addition, the HVLA thrust manipulation group had significantly (P<.001) greater improvement in both passive C1-2 rotation range of motion and motor performance of the deep cervical flexor muscles as compared to the group that received nonthrust mobilization. The number needed to treat to avoid an unsuccessful outcome was 1.8 and 2.3 at 48-hour follow-up, using the global rating of change and Neck Disability Index cut scores, respectively. CONCLUSION: The combination of upper cervical and upper thoracic HVLA thrust manipulation is appreciably more effective in the short term than nonthrust mobilization in patients with mechanical neck pain. LEVEL OF EVIDENCE: Therapy, level 1b. PMID- 21979311 TI - Protective role of antidiabetic drug metformin against gentamicin induced apoptosis in auditory cell line. AB - Besides their prominent function in cellular energy metabolism, the central role of mitochondria has been focused on control of cellular death in last decades. The mitochondrial permeability transition pore (PTP) is involved in the intrinsic pathway of apoptosis via the release of cytochrome c into cytosol. Metformin, a drug widely used in the treatment of type II diabetes, has recently received attention owing to new findings regarding its effect on apoptosis through mitochondrial permeability transition and cytochrome c release. The modulation of PTP is still unknown, but calcium is certainly the most important known inducer. In the present study, the preventive effects of metformin on gentamicin ototoxicity were investigated through the changes of intracellular calcium concentrations using calcium imaging in HEI-OC1 cells. Calcium imaging traced the changes of intracellular calcium concentration after the application of 50 mM of gentamicin in both 100 uM of metformin pretreated group and non-pretreated group. These calcium reactions were compared and analyzed with the results of cell viability test, Hoechst staining, intracellular reactive oxygen species level and expression of caspase-3, and poly-ADP-ribose polymerase (PARP). Continuous increase of intracellular calcium concentration (increase of 380/340 ratio) occurred after application of 50 mM of gentamicin. However, there was no change of intracellular calcium concentration in 100 uM metformin pretreated group. Cell viability was significantly higher in 100 uM metformin pretreated group and also, metformin pretreated HEI-OC1 cells produced less ROS that gentamicin alone treated group. Gentamicin increased cleaved PARP and caspase-3, but metformin inhibited the expression of caspase-3 and cleavage of PARP. This study demonstrated that metformin prevented gentamicin induced apoptosis through the calcium modulating and ROS reducing anti-apoptotic effects. PMID- 21979313 TI - Effects of hesperidin on the progression of hypercholesterolemia and fatty liver induced by high-cholesterol diet in rats. AB - The protective effects of hesperidin against hypercholesterolemia and fatty liver were examined in male Wistar rats fed a high-cholesterol diet for 12 weeks. Compared with a standard diet, a high-cholesterol diet not only increased body weights, liver weights, and serum concentration of cholesterol, but also induced the fatty degeneration (steatosis) of liver. Hesperidin (0.08%) reduced levels of hepatic steatosis, adipose tissue and liver weights (P < 0.05), serum total cholesterol and retinol binding protein (RBP) 4 concentrations (P < 0.05) in rats fed with high-cholesterol diet, while reduction in low-density lipoprotein cholesterol levels and triglyceride concentrations was not significant. It also attenuated the marked changes in mRNA expression of lipid metabolism-related proteins: RBP, heart fatty acid-binding protein (H-FABP), and cutaneous fatty acid-binding protein (C-FABP), in liver and adipose tissue. According to the results of gas chromatography, serum concentrations of total cholesterol and biomarkers of cholesterol synthesis (lathosterol) and absorption (campesterol, beta-sitosterol) were lower, and concentrations of cholesterol in feces were higher in the rats given hesperidin (P < 0.05). Hesperidin may improve hypercholesterolemia and fatty liver by inhibiting both the synthesis and absorption of cholesterol and regulating the expression of mRNA for RBP, C-FABP, and H-FABP. PMID- 21979314 TI - [Treat to target (T2T)]. PMID- 21979316 TI - [University contribution to implementation of the treat-to-target concept in rheumatology]. AB - Following similar examples for diabetes mellitus and hypertension an attempt was made to establish a treat-to-target (T2T) program for rheumatic diseases in order to improve the course of the disease. Nevertheless, it is a factum that rheumatology, a recognized discipline in internal medicine, was not represented in university clinics corresponding to its scientific, clinical and socioeconomic importance. On the question how rheumatology in university clinics can contribute to the implementation of a T2T program, several aspects have to be considered. These include improvement in training and further education, establishment of clinical scientific core topics, formulation of guidelines, initiation of controlled studies, establishment of long-term cohorts and the incorporation of pathogenetic and therapeutic information in international networks and national symposia. PMID- 21979315 TI - [Strategies for improved healthcare of people with the endemic disease rheumatism exemplified by rheumatoid arthritis]. AB - New therapeutic principles and considerable diagnostic advances have made it possible to define different rheumatic diseases and especially rheumatoid arthritis (RA) at an early stage and by starting an early and aggressive medication a considerable proportion of patients with RA will reach the status of low disease activity or even remission. With the additional development of composite measures to estimate the disease activity of RA, it was the goal of an international working group consisting of rheumatologists and patients to develop recommendations for treating rheumatoid arthritis in a similar way as for patients with hypertension or diabetes, with the aim to achieve remission as often as possible. This treat-to-target initiative has taken off in quite a number of different countries including Germany leading to discussions on how this initiative can be integrated into the specific national healthcare systems and what possibilities would exist for its implementation. To develop strategies for an improved healthcare of people suffering from rheumatic diseases and using RA as an example, action elements and postulates were developed which will be discussed in more detail in the present manuscript. PMID- 21979317 TI - [Treat-to-target (T2T) from the perspective of inpatient rheumatology]. AB - Publication of the treat-to-target (T2T) concept at the end of the Bone and Joint Decade almost coincided with the 15 treatment recommendations of the EULAR as well as with the new classification and revised remission criteria for rheumatoid arthritis (RA).The treat-to-target initiative is solely focused on the description of benchmarks for an effective treatment management of RA to reach its priority target of remission.From the perspective of inpatient rheumatology parallels are shown to the quality projects of the Association of Rheumatology Clinics (VRA), which were initiated in 2001 for the first time.The quality management started up by the VRA not only benefited from the development of the German diagnosis-related groups (G-DRG) system which was also supported by the VRA and the German Society of Rheumatology (DGRh) but also from projects realized to improve the structural and operational quality in inpatient rheumatology units.By launching its own outcome benchmarking project (OBRA) in 2003, which was financially supported by the German Ministry of Health and its continuation with Kobra-1 and future Kobra-2, the VRA already successfully incorporated all benchmarks of management guidelines outlined in the T2T initiative.By steadily improving the outcome, even of RA patients, inpatient rheumatology offers a special quality project for participating clinics who are otherwise competitors, not only to learn from each other but to support each other to find the best way (T2T) to reach a remission and a good quality of life for RA patients and patients with other systemic rheumatic diseases. PMID- 21979318 TI - [Treat-to-target from the perspective of office-based rheumatology]. AB - The development of evidence-based treat-to-target (T2T) recommendations alleviates decision-making for the rheumatologist and simultaneously promises substantial improvement of outcome for rheumatoid arthritis (RA) patients. For the office-based rheumatologist in Germany, however, implementation of T2T recommendations contains several difficulties. Limitations arise as a result of an insufficient number of rheumatologists as well as a lack of adequate remuneration both resulting in a lack of time for the individual RA patient. Furthermore budget limitations hinder the appropriate use of antirheumatic drugs and insofar counteract treating to the target of remission. Establishment of selective contracts for rheumatologists by health insurance funds might reduce many of these problems in future for the office-based rheumatologist in Germany. PMID- 21979319 TI - [Curriculum for "Rheumatology health professionals DGRh-BDRh" as a way of qualification for clinical nursing specialists : Concept and results of an evaluation]. AB - Rheumatological care in Germany is influenced by limited resources and education and qualification of health professionals is a way to optimize utilization of these resources.The curriculum for rheumatology health professionals of the Academy of the German Association of Rheumatologists (DGRh) was developed to qualify clinical nursing specialists of rheumatology clinics as well as specialized rheumatology hospitals on a systematic basis.Since 2006 499 participants have each been trained over 4 weekends and certification was achieved by examinations. The topics cover the principles of anatomy and the pathology of diseases up to modern diagnostic methods and treatment, including practical skills. Additional specialized courses for nurses of rheumatology hospitals and refresher courses give the participants the opportunity to increase their depth of knowledge.After 8 of the basic courses questionnaires were sent to all participants for evaluation and 143 (51%) out of 277 participants responded. Of the responders 95% found that their knowledge of understanding rheumatic diseases improved considerably or very considerably, 90% found that their ability to determine urgent cases and 86% to correctly judge emergency situations had improved and 50% agreed with the statement that their field of work and their tasks had changed after the training courses. Increased responsibilities, documentations of patient history, involvement in clinical trials and infusions and information of the patients about their disease or the treatment were listed as new tasks of the participants. In conclusion the evaluation shows that the curriculum for rheumatology health professionals is an effective step towards qualification for clinical nursing specialists. We believe that this will support the work of medical doctors in rheumatology and will improve the quality of care for patients with rheumatic diseases. PMID- 21979320 TI - [Treat-to-target from the patient perspective]. AB - The international treat-to-target initiative including rheumatoid arthritis (RA) patients has defined remission or alternatively low disease activity as treatment goals. In Germany representatives of the medical profession, such as doctors, nurses and including the Deutsche Rheuma-Liga, are deliberating how to adapt and realize these goals in practice. The patient's perspective has to be taken into consideration as an outcome variable. Until now no combined patient reported outcome (PRO) score exists which is generally accepted by the scientific community and which puts the patient's perspective as the main primary outcome.Patients and doctors ought to decide jointly about the therapy goal remission/low disease activity and about other PROs and the planned strategy to achieve these goals. A precondition is that a sufficient timeframe is still available for this. The joint target of the medical profession and the Deutsche Rheuma-Liga is 1 rheumatologist per 50,000 adult inhabitants. An interdisciplinary and multidisciplinary treatment of RA patients is just as imperative as the expansion of patient training, information and self-management programs. PMID- 21979321 TI - [T-cells in ANCA-associated vasculitis]. AB - CD4+NKG2D+effector memory T-cell-mediated endothelial cell damage and a Th17 dominated cytokine profile of PR3-specific T-cells may play an important role in the pathogenesis of granulomatosis with polyangiitis (Wegener's). The anti-IL-5 antibody mepolizumab (anti-IL-5) induces remission in Churg-Strauss syndrome. PMID- 21979322 TI - [Further education: a core responsibility of the German Society for Rheumatology and the Rheuma Academy]. AB - The first further education training program of the German Society of Rheumatology (DGRh) was an important milestone in further training in rheumatology. The workshop presented approaches on how to interest and gain students and young physicians for rheumatology and presented the possibilities planned by the DGRh in cooperation with partner organizations and the Rheuma Academy for improvement of further training in rheumatology and the potential to benefit inpatient further training. Many of the projects are dependent on financial support especially by industry. In this article the most important theses and arguments from the individual lectures will be presented. PMID- 21979323 TI - [How to finance and increase the appeal of rheumatology training : view of the Association of Rheumatology Clinics in Germany (VRA) on challenges and successful strategies]. AB - Due to the general lack of physicians in German hospitals new approaches are necessary to be successful in acquiring doctors for training in inpatient rheumatology.Although the financing of rheumatology education is still included in the general payment of hospitals, currently the diagnoses-related groups,,as it has already been fixed in the regulation on hospital care rates in Germany since 1994, new strategies may help to improve the financial situation of hospital units.The implementation of a binding structural quality, endorsed by the Association of Rheumatology Clinics in Germany (VRA), as well as the application of clinical pathways will optimize revenues.Further financial improvements can result from the implementation of case management, the implementation of interdisciplinary treatment, the promotion of a high quality treatment, from a differentiated approach towards outpatient treatment and a specialization within inpatient rheumatology units.Incorporating these strategies the advantages may not only affect the financial situation of hospitals but may also offer valuable incentives for physicians to start their professional career in inpatient rheumatology. PMID- 21979327 TI - Sodium chloride improves photosynthesis and water status in the succulent xerophyte Zygophyllum xanthoxylum. AB - Zygophyllum xanthoxylum, a C(3) woody species, is a succulent xerophyte that is well adapted to arid environments. Our previous investigations showed that Na(+) has a positive effect on the growth of Z. xanthoxylum under drought conditions, which was closely related to high Na(+) accumulation in leaves. To reveal the physiological mechanisms underlying how Na(+) accumulation improves the drought resistance of Z. xanthoxylum, 3-week-old seedlings were treated with a series of additional external NaCl concentrations (5-150 mM) in sand culture experiments. Seedlings were also subjected to water deficit (30% of field water capacity) in the presence or absence of additional NaCl (50 mM) in pot experiments. The results indicated that 50 mM NaCl could mitigate deleterious impacts of water deficit on the growth of Z. xanthoxylum, by improving the relative water content, inducing a significant drop in leaf water potential and, concomitantly, increasing leaf turgor pressure and chlorophyll concentrations resulting in an enhancement of overall plant photosynthetic activity (i.e., photosynthetic rate and water use efficiency). Furthermore, NaCl (50 mM) could alleviate the inhibitory effect of water deficit on the activity of photosystem II in Z. xanthoxylum. The contribution of Na(+) to the total osmotic potential varied from 8% in the control to 13% in plants subjected to water deficit and, surprisingly, to 28% in plants grown in the presence of 50 mM NaCl under water deficit; however, the contribution of K(+) significantly decreased from 13 to 8%. These findings suggest that, under arid environments, Z. xanthoxylum is able to accumulate a high concentration of Na(+) in its leaves and use it directly for osmotic adjustment, which was coupled with an improvement in leaf hydration and photosynthetic activity. PMID- 21979328 TI - Does action planning moderate the intention-habit interaction in the exercise domain? A three-way interaction analysis investigation. AB - Both habit strength and action planning have been found to moderate the intention exercise behaviour relationship, but no research exists that has investigated how habit strength and action planning simultaneously influence this relationship. The present study was designed to explore this issue in a prospective sample of undergraduate students (N = 415): action planning, habit strength, intention, attitudes, subjective norms and perceived behavioural control were assessed at baseline and exercise behaviour was assessed 2 weeks later. Both habit strength and action planning moderated the intention-exercise relationship, with stronger relationship at higher levels of planning or habit strength. Decomposing a significant action planning * habit strength * intention interaction showed that the strength of the intention-exercise relationship progressed linearly through levels of action planning and habit strength. These novel results show that action planning strengthens the intention-habit strength interaction in the exercise domain: exercise interventions should therefore focus on simultaneously bolstering action planning and habit strength. PMID- 21979330 TI - Fair comment. PMID- 21979329 TI - Genetic markers to discriminate benign and malignant thyroid nodules with undetermined cytology in an area of borderline iodine deficiency. AB - BACKGROUND: Fine needle aspiration (FNA) with cytologic evaluation is the most reliable tool for malignancy prediction in thyroid nodules, but cytologic diagnosis remains undetermined for 20% of nodules. AIM: We investigated the diagnostic potential of a set of 6 marker genes to distinguish benign and malignant thyroid nodules. SUBJECTS AND METHODS: The prospective study included 153 thyroid samples obtained by FNA of thyroid nodules from 151 patients (56 benign, 43 malignant, and 54 nodules with undetermined cytology). Gene expression was evaluated by quantitative realtime PCR and statistical analysis of data was performed. All samples were analyzed for V600E BRAF mutation. RESULTS: A decrease in TTF3 and HGD1 expression was observed in malignant nodules with respect to benign ones, while an increase in PLAB expression was demonstrated in these nodules. The decision model was valid for 88 of 99 cases of benign and malignant nodules, with a total of 11 false positive or negative predictions. The obtained malignant/benign phenotype prediction was also valid for 37 of 54 cases of nodules with undetermined cytology with a total of 8 false positive and 9 false negative predictions. V600E BRAF gene mutation was demonstrated in 19/43 malignant nodules, in 0/56 benign nodules, and in 1/54 undetermined nodules. CONCLUSIONS: The expression profiles of genes (TFF3, HGD1, and PLAB) allowed a good prediction for the differentiation of benign thyroid lesions and thyroid cancer starting from cells of FNA; however, this assay showed limitations when applied to discriminate thyroid nodules with undetermined cytology. PMID- 21979331 TI - Askew advice. PMID- 21979332 TI - Government let down. PMID- 21979333 TI - Freedom of information. PMID- 21979334 TI - Just another number? PMID- 21979335 TI - Spherical grey vesicles. PMID- 21979345 TI - Gingival recession: part 2. Surgical management using pedicle grafts. AB - This paper is the second in a three part series looking at the aetiology and management of gingival recession. Part one discussed the aetiology and non surgical management and this part aims to discuss the use of pedicle soft tissue grafts in the treatment of gingival recession. This article also considers the factors affecting the outcome of surgical procedures used to treat localised recession defects. The third paper in this series will consider the use of free soft tissue grafts and guided tissue regeneration. PMID- 21979350 TI - Summary of: Current practices and intention to provide alcohol-related health advice in primary dental care. PMID- 21979351 TI - Summary of: Are sugar-free confections really beneficial for dental health? PMID- 21979368 TI - Current practices and intention to provide alcohol-related health advice in primary dental care. AB - OBJECTIVES: To determine whether general dental practitioners (GDPs) currently provide alcohol-related advice (ARA) and to inform the development of an intervention, should one be required. METHOD: Cross-sectional postal survey of a random sample of 300 GDPs in Scotland. The questionnaire assessed beliefs derived from psychological models that explain behaviour in terms of beliefs that are amenable to change, and so may inform development of an intervention to encourage the provision of ARA. RESULTS: Sixty percent of GDPs responded. Eighty-three percent of participating GDPs (145/175) had not provided ARA to patients in the previous ten working days. Attitude (perceived consequences), control beliefs (perceived difficulty), subjective norm (perceived social pressure), and self efficacy (confidence) significantly predicted intention to provide ARA. Alcohol related knowledge or personal alcohol behaviour did not predict intention to provide ARA. CONCLUSIONS: There is scope to increase the provision of ARA in primary care dentistry and this study identified predictive beliefs, which could be targeted to encourage this behaviour. The next phase is to develop and test an intervention to encourage GDPs to provide ARA. PMID- 21979369 TI - Are sugar-free confections really beneficial for dental health? AB - BACKGROUND: Various sugar substitutes have been introduced and are widely used in confections and beverages to avoid tooth decay from sugar and other fermentable carbohydrates. One group of sugar substitutes are sugar alcohols or polyols. They have been specifically used in foods for diabetic patients because polyols are not readily absorbed in the intestine and blood stream, preventing post-prandial elevation of glucose level. Additionally they may lower caloric intake. METHODS: We searched PubMed, Cochrane Controlled Trials Registry, Cochrane Oral Health Review, Centre for Reviews and Dissemination in the UK, National Library for Public Health and a Centre for Evidence Based Dentistry website up to the end of October 2010, using the search terms 'sugar alcohol' or 'sugar-free' or 'polyols' and combined with a search with terms 'dental caries' or 'dental erosion'. RESULTS: Xylitol, a polyol, has been approved by the US Food and Drug Administration for its non-cariogenic properties that actually reduce the risk of dental decay and recently, the European Union also officially approved a health claim about xylitol as a 'tooth friendly' component in chewing gums. Although the presence of acidic flavourings and preservatives in sugar-free products has received less attention, these additives may have adverse dental health effects, such as dental erosion. Furthermore, the term sugar-free may generate false security because people may automatically believe that sugar-free products are safe on teeth. CONCLUSION: We concluded that polyol-based sugar-free products may decrease dental caries incidence but they may bring another dental health risk, dental erosion, if they contain acidic flavouring. There is a need for properly conducted clinical studies in this area. PMID- 21979370 TI - Administrative hospitalization database validation of cardiac procedure codes. AB - BACKGROUND: Although cardiac procedures are commonly used to treat cardiovascular disease, they are costly. Administrative data sources could be used to track cardiac procedures, but sources of such data have not been validated against clinical registries. OBJECTIVES: To examine accuracy of cardiac procedure coding in administrative databases versus a prospective clinical registry. SAMPLE: We examined a total of 182,018 common cardiac procedures including percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) surgery, valve surgery, and cardiac catheterization procedures during fiscal years 2005 and 2006 across 18 cardiac centers in Ontario, Canada. RESEARCH DESIGN: Accuracy of codes in the Canadian Institute for Health Information (CIHI) administrative databases were compared with the clinical registry of the Cardiac Care Network. RESULTS: Comparing 17,511 CIHI and 17,404 registry procedures for CABG surgery, the positive predictive value (PPV) of CIHI-coded CABG surgery was 97%. In 6229 CIHI coded and 5885 registry-coded valve surgery procedures, the PPV of the administrative data source was 96%. Comparing 38,527 PCI procedures in CIHI to 38,601 in the registry, the PPV of CIHI was 94%. Among 119,751 CIHI-coded and 111,725 registry-coded cardiac catheterization procedures, the PPV of administrative data was 94%. When the procedure date window was expanded from the same day to +/-1 days, the PPV was 96% (PCI) and exceeded 98% (CABG surgery), 97% (valve surgery), and 95% (cardiac catheterization). CONCLUSIONS: Using a clinical registry as the gold standard, the coding accuracy of common cardiac procedures in the CIHI administrative database was high. PMID- 21979371 TI - Identifying better practices for early-stage bladder cancer. AB - BACKGROUND: Practice guidelines for nonmuscle invasive (ie, early stage) bladder cancer are ambiguous, resulting in substantial practice variation without a clear patient benefit. OBJECTIVES: To profile urologist practice styles and empirically derive better patterns of use for common bladder cancer services. RESEARCH DESIGN: Retrospective cohort. SUBJECTS: Elderly patients diagnosed with early stage bladder cancer between January 1, 1992 and December 31, 2005 in Surveillance, Epidemiology, and End Results-Medicare linked data. MEASURES: After identifying each patient's treating urologist, we fit multilevel models to obtain reliability-adjusted measures of the urologist's use of surveillance-associated (cytoscopy and urine cytology) and treatment-associated (intravesical therapy) services during the 2 years after diagnosis. We then used the Cox proportional hazards regression to evaluate the association between a patient's risk of bladder cancer death and his urologist's frequency of service use. RESULTS: Regardless of disease severity, no measurable patient benefit was associated with care delivery by a urologist residing in the highest quartile for cystoscopy or intravescial therapy use. However, maximal intensity of cytology use was associated with a lower risk of bladder cancer death for patients with high-grade stage Ta/Tis (highest vs. lowest intensity quartiles: hazard ratio, 0.73; 95% confidence interval, 0.56-0.95) and stage T1 disease (hazard ratio, 0.59; 95% confidence interval, 0.49-0.72). CONCLUSIONS: Our analysis supports a more tailored approach to patients with early-stage bladder cancer. Further, it serves as an example for applying observational data to characterize better clinical practices in the absence of experimental studies. PMID- 21979372 TI - A fibroblast/macrophage co-culture model to evaluate the biocompatibility of an electrospun Dextran/PLGA scaffold and its potential to induce inflammatory responses. AB - Fibroblasts and macrophages are the two major types of cells responding to implanted biomaterials. They play crucial roles in inflammatory responses, host material interactions and tissue remodeling. However, the synergistic interactions of these two cell types with biomaterials are not fully understood. In this investigation, an in vitro fibroblast/macrophage co-culture system was utilized to examine the biocompatibility and the potential to induce inflammatory responses of an electrospun Dextran/PLGA scaffold. The scaffold did not affect the morphologies, attachments, proliferations and viabilities of both the fibroblasts and macrophages, cultured separately or together. Moreover, it only activated a small subset of the macrophages implicating a low potential to induce either severe acute or chronic inflammatory response. Additionally, fibroblasts played a role in prolonging macrophage activation in the presence of the scaffolds. Using antibody arrays, IL-10, SDF-1, MIP-1 gamma and RANTES were found to be up-regulated when the cells were incubated with the scaffolds. The results of subdermal implantation of the Dextran/PLGA scaffolds confirmed its biocompatibility and low inflammatory potential. PMID- 21979373 TI - Mediator coordinates PIC assembly with recruitment of CHD1. AB - Murine Chd1 (chromodomain helicase DNA-binding protein 1), a chromodomain containing chromatin remodeling protein, is necessary for embryonic stem (ES) cell pluripotency. Chd1 binds to nucleosomes trimethylated at histone 3 Lys 4 (H3K4me3) near the beginning of active genes but not to bivalent domains also containing H3K27me3. To address the mechanism of this specificity, we reproduced H3K4me3- and CHD1-stimulated gene activation in HeLa extracts. Multidimensional protein identification technology (MuDPIT) and immunoblot analyses of purified preinitiation complexes (PICs) revealed the recruitment of CHD1 to naive chromatin but enhancement on H3K4me3 chromatin. Studies in depleted extracts showed that the Mediator coactivator complex, which controls PIC assembly, is also necessary for CHD1 recruitment. MuDPIT analyses of CHD1-associated proteins support the recruitment data and reveal numerous components of the PIC, including Mediator. In vivo, CHD1 and Mediator are recruited to an inducible gene, and genome-wide binding of the two proteins correlates well with active gene transcription in mouse ES cells. Finally, coimmunoprecipitation of CHD1 and Mediator from cell extracts can be ablated by shRNA knockdown of a specific Mediator subunit. Our data support a model in which the Mediator coordinates PIC assembly along with the recruitment of CHD1. The combined action of the PIC and H3K4me3 provides specificity in targeting CHD1 to active genes. PMID- 21979374 TI - Opposing roles of NF-kappaB in anti-cancer treatment outcome unveiled by cross species investigations. AB - In malignancies, enhanced nuclear factor-kappaB (NF-kappaB) activity is largely viewed as an oncogenic property that also confers resistance to chemotherapy. Recently, NF-kappaB has been postulated to participate in a senescence-associated and possibly senescence-reinforcing cytokine response, thereby suggesting a tumor restraining role for NF-kappaB. Using a mouse lymphoma model and analyzing transcriptome and clinical data from lymphoma patients, we show here that therapy induced senescence presents with and depends on active NF-kappaB signaling, whereas NF-kappaB simultaneously promotes resistance to apoptosis. Further characterization and genetic engineering of primary mouse lymphomas according to distinct NF-kappaB-related oncogenic networks reminiscent of diffuse large B-cell lymphoma (DLBCL) subtypes guided us to identify Bcl2-overexpressing germinal center B-cell-like (GCB) DLBCL as a clinically relevant subgroup with significantly superior outcome when NF-kappaB is hyperactive. Our data illustrate the power of cross-species investigations to functionally test genetic mechanisms in transgenic mouse tumors that recapitulate distinct features of the corresponding human entity, and to ultimately use the mouse model-derived genetic information to redefine novel, clinically relevant patient subcohorts. PMID- 21979375 TI - Control of the senescence-associated secretory phenotype by NF-kappaB promotes senescence and enhances chemosensitivity. AB - Cellular senescence acts as a potent barrier to tumorigenesis and contributes to the anti-tumor activity of certain chemotherapeutic agents. Senescent cells undergo a stable cell cycle arrest controlled by RB and p53 and, in addition, display a senescence-associated secretory phenotype (SASP) involving the production of factors that reinforce the senescence arrest, alter the microenvironment, and trigger immune surveillance of the senescent cells. Through a proteomics analysis of senescent chromatin, we identified the nuclear factor kappaB (NF-kappaB) subunit p65 as a major transcription factor that accumulates on chromatin of senescent cells. We found that NF-kappaB acts as a master regulator of the SASP, influencing the expression of more genes than RB and p53 combined. In cultured fibroblasts, NF-kappaB suppression causes escape from immune recognition by natural killer (NK) cells and cooperates with p53 inactivation to bypass senescence. In a mouse lymphoma model, NF-kappaB inhibition bypasses treatment-induced senescence, producing drug resistance, early relapse, and reduced survival. Our results demonstrate that NF-kappaB controls both cell-autonomous and non-cell-autonomous aspects of the senescence program and identify a tumor-suppressive function of NF-kappaB that contributes to the outcome of cancer therapy. PMID- 21979377 TI - Rapid prototyping polymers for microfluidic devices and high pressure injections. AB - Multiple methods of fabrication exist for microfluidic devices, with different advantages depending on the end goal of industrial mass production or rapid prototyping for the research laboratory. Polydimethylsiloxane (PDMS) has been the mainstay for rapid prototyping in the academic microfluidics community, because of its low cost, robustness and straightforward fabrication, which are particularly advantageous in the exploratory stages of research. However, despite its many advantages and its broad use in academic laboratories, its low elastic modulus becomes a significant issue for high pressure operation as it leads to a large alteration of channel geometry. Among other consequences, such deformation makes it difficult to accurately predict the flow rates in complex microfluidic networks, change flow speed quickly for applications in stop-flow lithography, or to have predictable inertial focusing positions for cytometry applications where an accurate alignment of the optical system is critical. Recently, other polymers have been identified as complementary to PDMS, with similar fabrication procedures being characteristic of rapid prototyping but with higher rigidity and better resistance to solvents; Thermoset Polyester (TPE), Polyurethane Methacrylate (PUMA) and Norland Adhesive 81 (NOA81). In this review, we assess these different polymer alternatives to PDMS for rapid prototyping, especially in view of high pressure injections with the specific example of inertial flow conditions. These materials are compared to PDMS, for which magnitudes of deformation and dynamic characteristics are also characterized. We provide a complete and systematic analysis of these materials with side-by-side experiments conducted in our lab that also evaluate other properties, such as biocompatibility, solvent compatibility, and ease of fabrication. We emphasize that these polymer alternatives, TPE, PUMA and NOA, have some considerable strengths for rapid prototyping when bond strength, predictable operation at high pressure, or transitioning to commercialization are considered important for the application. PMID- 21979376 TI - Brain iron dysregulation and the risk of ageing white matter lesions. AB - White matter lesions (WML) or leukoaraiosis is a major feature in cerebral imaging of older people, and their prevalence increases with age. The clinical effects of WML vary with the main impairment being detected in the cognitive functions, increased risk of severe depression and motor impairment. Although vascular comorbidities have been found to be the main changes in these brains, increased production of reactive oxygen species (ROS) could represent a risk factor for these lesions with elemental iron being a potential factor for ROS production. This study focuses on changes in iron, iron-regulating proteins and RNA expression of iron metabolism genes. Three groups of samples were used: WML, normal areas from lesional WM [NAWM (L)] as disease control and normal WM from control brains [NAWM(C)]. Ferric iron staining was undertaken using known Perl's reaction. Immunohistochemistry (IHC) of white matter for ceruloplasmin (Cp), haemochromatosis (HFE) and transferrin receptor (TfR) was done. Cellular localization of HFE and Cp was performed using dual-antibody IHC. Whole-genome RNA was extracted from WML, NAWM (L) and NAWM(C), and QPCR for HFE, TF, TfR, ceruloplasmin, ferritin and ferroportin was performed. Ferric iron staining shows increased diffuse iron staining among WML, followed by NAWM (L) and the least group being NAWM(C). IHC shows increased HFE and CP expression in lesional WM, while TfR shows no changes among the groups. HFE colocalized with vascular endothelium and microglia in WML and control samples, while Cp colocalized with microglia and some expression was shown by astrocytes. The mRNA expression using QPCR suggests a pattern that favours decreased intracellular iron influx, increased ferrous oxidation and increased iron export from the cells. Iron metabolism seems to be changed in brains with WML, increased elemental iron in these brains and in turn increased production of free oxidative radicals could represent a potentiating factor for the development of ageing WML. PMID- 21979378 TI - Diabetes does not influence activation of coagulation, fibrinolysis or anticoagulant pathways in Gram-negative sepsis (melioidosis). AB - Diabetes is associated with a disturbance of the haemostatic balance and is an important risk factor for sepsis, but the influence of diabetes on the pathogenesis of sepsis remains unclear. Melioidosis ( Burkholderia pseudomallei infection) is a common cause of community-acquired sepsis in Southeast Asia and northern Australia. We sought to investigate the impact of pre-existing diabetes on the coagulation and fibrinolytic systems during sepsis caused by B.pseudomallei . We recruited a cohort of 44 patients (34 with diabetes and 10 without diabetes) with culture-proven melioidosis. Diabetes was defined as a pre admission diagnosis of diabetes or an HbA1c>7.8% at enrolment. Thirty healthy blood donors and 52 otherwise healthy diabetes patients served as controls. Citrated plasma was collected from all subjects; additionally in melioidosis patients follow-up specimens were collected seven and >= 28 days after enrolment where possible. Relative to uninfected healthy controls, diabetes per se (i.e. in the absence of infection) was characterised by a procoagulant effect. Melioidosis was associated with activation of coagulation (thrombin-antithrombin complexes (TAT), prothrombin fragment F1+2 and fibrinogen concentrations were elevated; PT and PTT prolonged), suppression of anti-coagulation (antithrombin, protein C, total and free protein S levels were depressed) and abnormalities of fibrinolysis (D-dimer and plasmin-antiplasmin complex [PAP] were elevated). Remarkably, none of these haemostatic alterations were influenced by pre-existing diabetes. In conclusion, although diabetes is associated with multiple abnormalities of coagulation, anticoagulation and fibrinolysis, these changes are not detectable when superimposed on the background of larger abnormalities attributable to B. pseudomallei sepsis. PMID- 21979379 TI - Drugs of abuse and the immune system in perspective. PMID- 21979380 TI - Task-induced deactivation and the "resting" state. AB - Task-induced decreases in blood flow and the widespread use of "resting" baselines produced unexpected and discrepant results in early cognitive imaging studies, especially in language comprehension experiments. Here I describe from a personal perspective some of the events and thought processes leading to the first hypothesis-driven fMRI study of the "resting" state. PMID- 21979381 TI - Single, slice-specific z-shim gradient pulses improve T2*-weighted imaging of the spinal cord. AB - T2*-weighted imaging of the spinal cord suffers from signal dropouts that hamper blood-oxygenation-level-dependent functional magnetic resonance imaging (fMRI). They are due to field inhomogeneities caused by the different magnetic susceptibilities of the vertebrae and the intervertebral disks that vary periodically along the cord and, thus, cannot be compensated appropriately with conventional (constant) shimming. In this study, a single, slice-specific gradient pulse ("z-shim") is applied in echo-planar imaging of axial sections in order to compensate for the corresponding through-slice signal dephasing without affecting the acquisition time, i.e. the temporal resolution. Based on a reference acquisition sampling a range of compensation moments, the value yielding the maximum signal amplitude within the spinal cord is determined for each slice. Severe N/2 ghosting for larger compensation moments is avoided by applying the gradient pulse after the corresponding reference echoes. Furthermore, first-order flow compensation in the slice direction of both the slice-selection and the z-shim gradient pulse considerably reduces signal fluctuations in the cerebro-spinal fluid surrounding the spinal cord, i.e. would minimize ringing artifacts in fMRI. Phantom and in vivo experiments show the necessity to use slice-specific compensation moments in the presence of local susceptibility differences. Measurements performed in a group of 24 healthy volunteers at 3T demonstrate that this approach improves T2*-weighted imaging of axial sections of the cervical spinal cord by (i) increasing the signal intensity (overall by about 20%) and (ii) reducing signal intensity variations along the cord (by about 80%). Thus, it may help to improve the feasibility and reliability of fMRI of the spinal cord. PMID- 21979382 TI - FSL. AB - FSL (the FMRIB Software Library) is a comprehensive library of analysis tools for functional, structural and diffusion MRI brain imaging data, written mainly by members of the Analysis Group, FMRIB, Oxford. For this NeuroImage special issue on "20 years of fMRI" we have been asked to write about the history, developments and current status of FSL. We also include some descriptions of parts of FSL that are not well covered in the existing literature. We hope that some of this content might be of interest to users of FSL, and also maybe to new research groups considering creating, releasing and supporting new software packages for brain image analysis. PMID- 21979384 TI - Towards a resolution of conflicting models of illusory contour processing in humans. AB - Despite myriad studies, neurophysiologic mechanisms mediating illusory contour (IC) sensitivity remain controversial. Among the competing models one favors feed forward effects within lower-tier cortices (V1/V2). Another situates IC sensitivity first within higher-tier cortices, principally lateral-occipital cortices (LOC), with later feedback effects in V1/V2. Still others postulate that LOC are sensitive to salient regions demarcated by the inducing stimuli, whereas V1/V2 effects specifically support IC sensitivity. We resolved these discordances by using misaligned line gratings, oriented either horizontally or vertically, to induce ICs. Line orientation provides an established assay of V1/V2 modulations independently of IC presence, and gratings lack salient regions. Electrical neuroimaging analyses of visual evoked potentials (VEPs) disambiguated the relative timing and localization of IC sensitivity with respect to that for grating orientation. Millisecond-by-millisecond analyses of VEPs and distributed source estimations revealed a main effect of grating orientation beginning at 65 ms post-stimulus onset within the calcarine sulcus that was followed by a main effect of IC presence beginning at 85 ms post-stimulus onset within the LOC. There was no evidence for differential processing of ICs as a function of the orientation of the grating. These results support models wherein IC sensitivity occurs first within the LOC. PMID- 21979383 TI - Roles for the pre-supplementary motor area and the right inferior frontal gyrus in stopping action: electrophysiological responses and functional and structural connectivity. AB - Both the pre-supplementary motor area (preSMA) and the right inferior frontal gyrus (rIFG) are important for stopping action outright. These regions are also engaged when preparing to stop. We aimed to elucidate the roles of these regions by harnessing the high spatio-temporal resolution of electrocorticography (ECoG), and by using a task that engages both preparing to stop and stopping outright. First, we validated the task using fMRI in 16 healthy control participants to confirm that both the preSMA and the rIFG were active. Next, we studied a rare patient with intracranial grid coverage of both these regions, using macrostimulation, diffusion tractography, cortico-cortical evoked potentials (CCEPs) and task-based ECoG. Macrostimulation of the preSMA induced behavioral motor arrest. Diffusion tractography revealed a structural connection between the preSMA and rIFG. CCEP analysis showed that stimulation of the preSMA evoked strong local field potentials within 30 ms in rIFG. During the task, when preparing to stop, there was increased high gamma amplitude (~70-250 Hz) in both regions, with preSMA preceding rIFG by ~750 ms. For outright stopping there was also a high gamma amplitude increase in both regions, again with preSMA preceding rIFG. Further, at the time of stopping, there was an increase in beta band activity (~16 Hz) in both regions, with significantly stronger inter-regional coherence for successful vs. unsuccessful stop trials. The results complement earlier reports of a structural/functional action control network between the preSMA and rIFG. They go further by revealing between-region timing differences in the high gamma band when preparing to stop and stopping outright. They also reveal strong between-region coherence in the beta band when stopping is successful. Implications for theories of action control are discussed. PMID- 21979385 TI - Developmental effects related to angiogenesis and osteogenic differentiation in Salmon larvae continuously exposed to dioxin-like 3,3',4,4'-tetrachlorobiphenyl (congener 77). AB - We have studied the effects of dioxin-like 3,3',4,4'-tetrachlorobiphenyl (PCB-77) on developmental effects related to angiogenesis and osteogenesis during early life-stages of salmon. Larvae were kept at 6 degrees C and continuously exposed to waterborne PCB-77 (1 or 10 ng/L) initiated at the egg stage or 416-day degrees (dd) and throughout yolk-sac stage (716 dd) and for a total duration of 50 days (or 300 dd). Gene transcription analysis was performed on whole larvae total RNA at 548, 632, 674 and 716 dd using real-time PCR. Bone morphogenetic protein (bmp2 and bmp4), transforming growth factor beta (TGF-beta), estrogen receptors (ERalpha and ERbeta), runx2, sox9 and collagen type 2 alpha 1 (col2a1) and vascular endothelial growth factor (VEGF) genes were studied. Effect on VEGF gene transcription was related to observation of heart rate, arrhythmia and anemia, demonstrating effects on vascular system development. Alizarine-red staining and quantification of ossified bone structures showed that PCB-77 produced concentration-dependent increases in the rate of osteogenic tissue formation. PCB 77 produced increases in col2a1 and runx2 transcription with subsequent induction of chondrogenesis and osteogenesis, respectively. The transcription of TGF-beta gene was associated with ERbeta transcription. Transcripts of AhR gene battery were differentially modulated by PCB-77 and these effects were dependent on concentration and larval age. Evidence of vascular system disruption by PCB-77 was observed as cardiac edema, anemia and arrhythmia in exposed individuals and as decreased level of VEGF gene transcription at early age. In general, our data indicate that PCB-77 produced developmental effects related to angiogenesis and osteogenic differentiation and disruption of vascular system development. PMID- 21979386 TI - Continent women have better urethral neuromuscular function than those with stress incontinence. AB - INTRODUCTION AND HYPOTHESIS: The objective of this study is to describe urethral neuromuscular function using concentric needle electromyography (EMG) in stress incontinent (SUI) and asymptomatic women. METHODS: Following Institutional Review Board approval, we recruited SUI and asymptomatic women without urinary incontinence. Participants underwent quantitative urethral EMG and urodynamic testing. RESULTS: Sixty-seven women (37 SUI, 30 continent) with mean +/- SD age of 44 +/- 12 years participated. Nearly all EMG parameters showed significant differences between continent and SUI women consistent with better motor unit recruitment in continent women. Continent women had larger-amplitude, longer duration motor unit action potentials (MUP) with increased turns and better MUP recruitment during bladder filling (P < .05). Increasing age was inversely correlated with nearly all MUP parameters (P < .05), suggesting MUP to be consistent with neuropathy. CONCLUSIONS: We found significant differences in multiple MUP parameters in urethral sphincter between continent and stress incontinent women, suggesting continent women have better urethral innervation. We also found significant neuropathic MUP changes with advancing age, regardless of continence status. PMID- 21979387 TI - The role of clinical neurophysiology in urogynecology. AB - INTRODUCTION: Clinical neurophysiological methods remain interesting research tools in urogynecology; their diagnostic role in the individual "pelvic floor" patient is, however, minor. CONCLUSION: The methods are diagnostically useful particularly in patients suspected to have a lesion involving the sphincters or the peripheral sacral nervous system, the diagnosis of which will influence management decisions or have prognostic or medicolegal relevance. Most helpful tests are the concentric needle EMG and bulbocavernosus reflex testing. PMID- 21979388 TI - Risks, symptoms, and management of pelvic nerve damage secondary to surgery for pelvic organ prolapse: a report of 95 cases. AB - INTRODUCTION AND HYPOTHESIS: This study aims to report pelvic nerve damage secondary to surgical treatment of pelvic organ prolapse and the role of laparoscopy in the diagnosis and treatment of such nerve damage. METHODS: Ninety five consecutive patients complaining of pain and/or bladder or bowel dysfunction following surgery for pelvic prolapse underwent laparoscopic exploration for pelvic neuropathy. RESULTS: A mean reduction in visual analog score (VAS) from 8.9 (+/- 0.96; 6-10) preoperatively to 2.9 (+/- 2.77; 0-6) at 1-year follow-up was obtained in patients after laparoscopic nerve decompression (n = 90; p < 0.001). Success, defined as a reduction in VAS score of greater than 50%, was obtained in 84% of patients. Sixty-five patients (68%) discontinued the regular use of analgesics. CONCLUSIONS: Because secondary nerve damage can appear months or years after the primary procedure, long-term follow-up is mandatory and should focus on nerve damage as well as anatomical and functional outcomes. Laparoscopy is a unique method for etiologic diagnosis and neurosurgical treatment of such nerve lesions through decompression or implantation of an electrode for neuromodulation. PMID- 21979389 TI - Neurophysiology in urogynaecology. PMID- 21979390 TI - Prospective associations between measures of adiposity and periodontal disease. AB - Obesity induced inflammation may promote periodontal tissue destruction and bone resorption inducing tooth loss. We examined the association between measures of adiposity and self-reported periodontal disease, using data from 36,910 healthy male participants of the Health Professionals Follow-Up Study (HPFS) who were free of periodontal disease at baseline and followed for <=20 years (1986-2006). Self-reported height, weight, and periodontal disease data were collected at baseline, weight and periodontal disease were additionally collected on biennial follow-up questionnaires and waist and hip circumference were self-reported in 1987. These self-reported measures have been previously validated. The multivariable adjusted associations between BMI (kg/m(2)), waist circumference (WC), waist-to-hip ratio (WHR), and first report of periodontal disease diagnosis were evaluated using time-varying Cox models. We observed 2,979 new periodontal disease diagnoses during 596,561 person-years of follow-up. Significant associations and trends were observed between all measures of adiposity and periodontal disease after adjusting for age, smoking, race, dental profession, physical activity, fruit and vegetable intake, alcohol consumption, and diabetes status at baseline. BMI >=30 kg/m(2) compared to BMI 18.5-24.9 kg/m(2) was significantly associated with greater risk of periodontal disease (hazard ratios (HR) = 1.30; 95% confidence interval (CI): 1.17-1.45). Elevated WC and WHR were significantly associated with a greater risk of periodontal disease (HR for extreme quintiles: WC = 1.27, 95% CI: 1.11-1.46; WHR = 1.34, 95% CI: 1.17-1.54). The associations of BMI and WC were significant even among nondiabetics and never smokers. Given the high prevalence of overweight, obesity, and periodontal disease this association may be of substantial public health importance. PMID- 21979391 TI - Overproduction of angiotensinogen from adipose tissue induces adipose inflammation, glucose intolerance, and insulin resistance. AB - Although obesity is associated with overactivation of the white adipose tissue (WAT) renin-angiotensin system (RAS), a causal link between the latter and systemic insulin resistance is not established. We tested the hypothesis that overexpression of angiotensinogen (Agt) from WAT causes systemic insulin resistance via modulation of adipose inflammation. Glucose tolerance, systemic insulin sensitivity, and WAT inflammatory markers were analyzed in mice overexpressing Agt in the WAT (aP2-Agt mice). Proteomic studies and in vitro studies using 3T3-L1 adipocytes were performed to build a mechanistic framework. Male aP2-Agt mice exhibited glucose intolerance, insulin resistance, and lower insulin-stimulated glucose uptake by the skeletal muscle. The difference in glucose tolerance between genotypes was normalized by high-fat (HF) feeding, and was significantly improved by treatment with angiotensin-converting enzyme (ACE) inhibitor captopril. aP2-Agt mice also had higher monocyte chemotactic protein-1 (MCP-1) and lower interleukin-10 (IL-10) in the WAT, indicating adipose inflammation. Proteomic studies in WAT showed that they also had higher monoglyceride lipase (MGL) and glycerol-3-phosphate dehydrogenase levels. Treatment with angiotensin II (Ang II) increased MCP-1 and resistin secretion from adipocytes, which was prevented by cotreating with inhibitors of the nuclear factor-kappaB (NF-kappaB) pathway or nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. In conclusion, we show for the first time that adipose RAS overactivation causes glucose intolerance and systemic insulin resistance. The mechanisms appear to be via reduced skeletal muscle glucose uptake, at least in part due to Ang II-induced, NADPH oxidase and NFkappaB-dependent increases in WAT inflammation. PMID- 21979392 TI - Epicardial fat volume is associated with coronary microvascular response in healthy subjects: a pilot study. AB - Epicardial fat (EF) is an active ectopic fat depot, which has been associated with coronary atherosclerosis, and which could early influence endothelial function. We thus investigated the relationship between EF and endothelium dependent vasoreactivity of the coronary microcirculation, in highly selected healthy volunteers. Myocardial blood flow (MBF) was determined by measuring coronary sinus flow with velocity-encoded cine magnetic resonance imaging (MRI) at 3T. We measured MBF at baseline and in response to sympathetic stimulation by cold pressor testing (CPT) in 30 healthy volunteers with normal left ventricular (LV) function (age 22 +/- 4 years, BMI = 21.3 +/- 2.8 kg/m(2)). EF volume was volumetrically assessed by manual delineation on short-axis views. CPT was applied by immersing one foot in ice water for 4 min. Mean EF volume was 56 +/- 26 ml and mean LV mass 100 +/- 28 g. CPT significantly increased heart rate (HR) by 32 +/- 19%, systolic blood pressure by 14 +/- 10%, and rate-pressure product by 45 +/- 25%, P < 0.0001. The increase in HR, reflecting sympathetic stimulation, was not influenced by sex, age or EF volume. CPT induced a decrease in coronary vascular resistance (135 +/- 72 vs. 100 +/- 42 mm Hg.ml(-1).min.g, P = 0.0006), and a significant increase in MBF (0.81 +/- 0.37 vs. 1.24 +/- 0.56 ml.min(-1).g(-1), P < 0.0001). Interestingly, we found a significant negative correlation between EF volume and DeltaMBF (r= - 0.40, P = 0.03), which remained significant after adjusting for DeltaHR. DeltaMBF was also associated with adiponectin (r = 0.41, P = 0.046), but not with waist circumference, BMI, C reactive protein, lipid or glycemic parameters. In multivariate analysis, adiponectin and EF volume remained both independently associated with DeltaMBF. A high EF amount is associated with a lower coronary microvascular response, suggesting that EF could early influence endothelial function. PMID- 21979393 TI - A facile spin-cast route for cation exchange of multilayer perpendicularly aligned nanorod assemblies. AB - A facile spin cast route was developed to convert perpendicularly aligned nanorod assemblies of cadmium chalcogenides into their silver and copper analogues. The assemblies are rapidly cation exchanged without affecting either the individual rod dimensions or collective superlattice order extending over several multilayers. PMID- 21979395 TI - Inclusion of a spasmolytic in bowel cleansing: a prospective randomized study. AB - The quality of colon cleansing and the tolerance of patients to the procedure are two major determinants of the quality of a colonoscopy. Many bowel-cleansing regimens are known, but there is no ideal regimen. Alverine citrate (Relaxyl, Spasmonal) is a spasmolytic agent that has been shown to affect responses of mechanoreceptors of the intestine to both mechanical and chemical stimuli. Patients who underwent colonoscopies at four centers were randomly assigned two different bowel-cleansing procedures. The bowel-cleansing methods were oral sodium phosphate (NaP) (Group I) and oral NaP plus alverine citrate (Group II). Patients were randomized into one of these regimens. The quality of colon cleansing was assessed by an endoscopist with an empirical, clinically meaningful 3-point scale. Both groups were similar with respect to age, gender, and pre- and postcolonoscopic diagnosis. In Group I, 76 patients (47 women and 29 men; aged 39.53 +/- 7.87 years) and in Group II, 71 patients (41 women and 30 men; aged 39.78 +/- 8.27 years) were included in the study. In Groups I and II, 37 (48.7%) and 41 (57.7%) patients had perfect bowel cleansing, respectively. The overall colon cleansing in the group with NaP plus alverine citrate was comparable with that in the NaP group. The tolerability of patients to the colonoscopy in the two groups was also similar. Based on the present data, adding oral alverine citrate to NaP does not increase either the quality of bowel cleansing or the tolerance of patients to the procedure. PMID- 21979396 TI - Splenic injury due to colonoscopy: nursing considerations. AB - Complications associated with the performance of a colonoscopy are low. Splenic tearing or trauma postcolonoscopy is a rare but serious complication. Identification of a splenic injury is difficult because of the nonspecific nature of the patient's symptoms. A meta-analysis approach was used to identify common risk factors, onset and presentation of symptoms, and procedural difficulty associated with splenic injury postcolonoscopy. A review of 10 published case studies and 1 case presented by the author were compared with published findings for patients sustaining a splenic injury following colonoscopy. Potential common signs and symptoms as well as common risks factors were identified. Nursing considerations for the identification of high-risk patients and postprocedure symptoms are outlined. Early detection of this rare complication is difficult, but having a high level of suspicion can help to identify patients at risk for sustaining a splenic injury during colonoscopy. PMID- 21979397 TI - Splenic injury due to colonoscopy: nursing considerations. PMID- 21979398 TI - Vitamin D and calcium status and appropriate recommendations in bariatric surgery patients. AB - Bariatric surgery is becoming an increasingly common procedure performed to achieve long-term weight loss in morbidly obese patients. Bariatric surgery may cause long-term morbidity because of vitamin and mineral deficiencies. This review synthesizes the research on vitamin D and calcium status in obese patients before and after bariatric surgery. The literature shows that morbidly obese patients are likely deficient in vitamin D prior to surgery because of poor sunlight exposure, less bioavailability of the vitamin when sequestered in fat cells, and inhibited hepatic vitamin activation. Gastric bypass surgery may further exacerbate vitamin D and calcium deficiencies secondary to poor compliance, loss to follow-up, reduced food intake, and malabsorption. It is imperative that research be conducted to determine adequate supplementation regimens for vitamin D and calcium in bariatric surgery patients. PMID- 21979399 TI - Diabetic colon preparation comparison study. AB - The purpose of the present study was to establish an optimal colon preparation for persons with diabetes who are undergoing colonoscopies. Specifically, the aim was to compare the difference between an experimental and standard preparation. Adequacy of bowel preparation is critical for good bowel visualization. Compared with nondiabetic patients, persons with diabetes have slower gastric emptying, colonic transit, and colon evacuation. Inadequate preparations may lead to suboptimal colonoscopy resulting in overlooked pathology, repeated examinations with associated risks, and organizational inefficiencies. Using a single-blind experimental design, 198 persons with diabetes who were scheduled to receive colonoscopies were randomly assigned to either the experimental (diabetic colon preparation) or the control (standard colon preparation) group. Patients in the diabetic colon preparation group had 70% good colon preparations compared with 54% in the standard group, and this finding was significant (chi = 5.14, p = 0.02). Results indicate that diabetic patients receiving 10 ounces of magnesium citrate 2 days prior to their colonoscopies followed by 10 ounces of magnesium citrate and 4-L polyethylene glycol the day prior to the procedure had cleaner colons than those receiving standard preparation of 10 ounces of magnesium citrate and 4-L polyethylene glycol the day prior to procedure. This colon preparation is safe, feasible, well-tolerated, and effective. PMID- 21979401 TI - Patients' need for information prior to colonic surgery. AB - Perioperative information and communication between patients and health professionals is central to the quality of care and patient involvement for elective colon surgery. Enhanced recovery after surgery (ERAS) means that the care process is accelerated with comprehensive information and additional requirements on an individual. The purpose of this study was to identify nurses' and doctors' experience of patients' need for information before intraoperative care. Nurses (n = 39) with different specialties and professional experience were interviewed in focus groups. Ten anesthesiologists with differing professional experience were interviewed individually. Data were analyzed with qualitative content analysis. The result shows the need to provide information to reduce anxiety, to make the patient feel safe, to explain postoperative pain management, and to provide a comprehensive care pathway. There was no difference between the informants' perception of patients' information needs. All respondents agreed that patients generally have a great need for information. The perioperative information should be repeated at different points in time. The patients' need for information on diagnosis is recurrent. Knowledge, good communication, and attitude from a multiprofessional perspective support the patient's feeling comfortable and involved in the care prior to surgery. PMID- 21979400 TI - Interferon and the fear of needles: a case report. AB - The treatment of viral hepatitis C infection uses a combination of pegylated interferon and ribavirin. Psychological preparation of the patient is vital to ensure adherence to the treatment. In our center, the nurse prepares this treatment according to an established educative protocol; however, some patients have special needs that require individualized attention. One such situation observed by the nurse is that the patients frequently admit to the fear of needle puncture (the peginterferon treatment is administered subcutaneously) and are unable to inject themselves. We describe a representative case and the care plan to manage the patient's fear so that the patient acquires confidence in his or her ability to self-inject. This facilitates autonomy and coresponsibility for the treatment, and the nurse can develop care approaches to combat the patient's fear of needles. PMID- 21979402 TI - Propofol alert! PMID- 21979403 TI - An unusual complication of peptic ulcer disease: double pylorus. PMID- 21979404 TI - Abrupt change. PMID- 21979405 TI - The H2 dissociation on the BN, AlN, BP and AlP nanotubes: a comparative study. AB - The thermodynamic and kinetic feasibility of H(2) dissociation on the BN, AlN, BP and AlP zigzag nanotubes has been investigated theoretically by calculating the dissociation and activation energies. We determined the BN and AlP tubes to be inert toward H(2) dissociation, both thermodynamically and kinetically. The reactions are endothermic by 5.8 and 3 kcal mol(-1), exhibiting high activation energies of 38.8 and 30.6 kcal mol(-1), respectively. Our results indicated that H(2) dissociation is thermodynamically favorable on both PB and AlN nanotubes. However, in spite of the thermodynamic feasibility of H(2) dissociation on PB types, this process is kinetically unfavorable due to partly high activation energy. Generally, we concluded that among the four studied tubes, the AlN nanotube may be an appropriate model for H(2) dissociation process, from a thermodynamic and kinetic stand point. We also indicated that H(2) dissociation is not homolytic, rather it takes place via a heterolytic bond cleavage. In addition, a comparative study has been performed on the electrical and geometrical properties of the tubes. Our analysis showed that the electrical conductivity of tubes is as follows: BP>AlP>BN>AlN depending on how to combine the electron rich and electron poor atoms. PMID- 21979406 TI - SM2(+/-) male mice are predisposed to develop urinary tract obstruction and hyper contractility of the bladder smooth muscle upon ageing. AB - We previously showed that complete loss of smooth muscle myosin heavy chain isoform 2 (SM2) resulted in postnatal lethality, but in het mice a partial loss of SM2 (SM2(+/-)) was accompanied by down-regulation of SM1 with unaltered SM2:SM1 ratio. To determine whether a normal bladder function would be maintained throughout its lifespan, we aged WT and SM2(+/-) mice up to 18 months and analyzed a) SM2:SM1 ratio b) bladder smooth muscle structure and c) function in SM2(+/-) het mice. A notable finding was that ~50% of 15-18 months old male SM2(+/-) mice exhibited urinary retention in bladder with the distention of upper urethra. In SM2(+/-) mouse bladder with urinary retention, the SM2:SM1 ratio was decreased but not in SM2(+/-) mouse bladder that did not develop urinary retention. Interestingly in the distended bladder the expression levels of alpha actin and tropomyosin remained unaltered despite a reduction in the number of myosin thick filaments. These distended bladders showed hypersensitivity to submaximal K(+) depolarization and M3-receptor stimulation, without a significant increase in myosin light chain phosphorylation. We therefore suggest that a partial loss of SM2 may predispose male mice to develop lower urinary tract obstruction during ageing. In addition our data suggest that bladder obstruction can cause a further reduction in SM2 expression and SM2:SM1 ratio, and a hyper contractility of the bladder smooth muscle. PMID- 21979407 TI - The effect of omeprazole on gastric myoelectrical activity and emptying. AB - Omeprazole, a proton pump inhibitor, is widely used for the treatment of patients with peptic ulcer, gastroesophageal reflux disease and functional dyspepsia (FD), although some studies have demonstrated that omeprazole delays gastric emptying. The purpose of this study was to investigate the efficacy of omeprazole on gastric motility including gastric myoelectrical activity and gastric emptying. This study was performed on 12 healthy volunteers. Gastric motility was evaluated with cutaneously recorded electrogastrography (EGG) and gastric emptying of semi solid meals using the (13)C-acetic acid breath test. EGG and gastric emptying were measured before and after treatment with 20 mg omeprazole orally for 7 days. In the fasting state, the percentage of EGG normogastria increased significantly compared to the baseline. No significant changes were observed in other EGG parameters including the percentage of tachygastria and bradygastria in both fasting and postprandial states, and the power ratios between both before and after ingestion of omeprazole. In addition, administrated omeprazole did not show any significant differences in the gastric emptying parameters such as the half emptying time. We conclude that administration of omeprazole did not affect gastric motility but improved gastric myoelectrical activity. These effects of omeprazole may be one of the mechanisms involved in its efficacy in relieving dyspeptic symptoms in FD patients. PMID- 21979408 TI - Factors which determine the duration of follower potentials in longitudinal smooth muscle isolated from the guinea-pig stomach antrum. AB - In isolated longitudinal muscle tissues of the guinea-pig stomach antrum, recording electrical responses from smooth muscle cells revealed a periodical generation of follower potentials with variable durations. The I-D relationship, made by plotting the duration as a function of the interval before generating follower potential, was linear. Experiments were carried out to investigate the effects of chemicals which had been known to modulate the release of Ca(2+) from the internal stores (2-aminoethoxy-diphenyl-borate, cyclopiazonic acid, caffeine), inhibit mitochondrial metabolic activity (m-chlorophenyl hydrazone, 2 deoxy-D-glucose, potassium cyanide, rotenone), inhibit ATP-sensitive K-channels distributed in mitochondria (glibenclamide, 5-hydroxydecanoic acid) and inhibit the activity of proteinkinase C (chelerythrine), on the I-D relationship of follower potentials. The effects of depolarization on follower potentials were assessed by stimulating tissues with high potassium solution. Experiments were carried out mainly in the presence of nifedipine which minimized the movements of muscles with no modulation of follower potentials. Cycropiazonic acid and caffeine reduced the slope of I-D relationship, with associated reduction of the duration and frequency of follower potentials. 2-Aminoethoxydiphenyl borate reduced the duration and amplitude and increased the frequency of follower potentials, with depolarization of the membrane, and the effects were simulated by high potassium solution. m-Chlorophenyl hydrazone, potassium cyanide, 2-deoxy D-glucose, rotenone, 5-hydroxydecanoic acid and glibenclamide reduced the slope of I-D relationship, with associated reduction of the frequency of follower potentials. Chelerythrine did not modulate the slope of I-D relationship, with reduced frequency of follower potentials. It seemed likely that the amount of Ca(2+) released from the internal stores and also mitochondrial function had causal relationship to the duration of pacemaker potentials, suggesting that internal Ca-stores and mitochondria are taking the central role for determining the duration of the pacemaker activity. Proteinkinase C did not seem to participate to the function of mitochondria and internal Ca(2+) stores. PMID- 21979409 TI - Interstitial cells of Cajal in the gastrointestinal musculature of W(jic) c-kit mutant mice. AB - Interstitial cells of Cajal (ICC) generate electrical rhythmicity and transduce neural signals in the gastrointestinal musculature. ICC express the proto oncogene c-kit, a receptor tyrosine kinase, and are identified morphologically by c-Kit immunoreactivity. The c-kit gene is allelic with the murine white-spotting locus W, and mutations of c-kit are known as W mutations. W mutations affect various developmental aspects of hematopoietic cells, germ cells, melanocytes, mast cells and ICC. We examined W(jic)/W(jic) mutant mice that have a mutation in the tyrosine kinase domain resulting in severe loss of protein function. W(jic)/W(jic) homozygotes exhibited white coats and black eyes. The gross morphology of the gastrointestinal tract showed no abnormality in mutant mice other than a forestomach papilloma. In the stomach, intramuscular ICC (ICC-IM) were missing, and myenteric ICC (ICC-MY) were reduced in number. In the small intestine, the number of ICC-MY was severely reduced; however there was a normal distribution of deep muscular plexus ICC (ICC-DMP). In the cecum, the numbers of ICC-IM and ICC-MY were severely depleted. ICC-IM were almost entirely absent in the colon, whereas ICC-MY loss was restricted to the distal colon. Patterns of ICC deficiency were generally similar between W(jic)/W(jic) mice and W/W(v) mutants, which lack a specific type of ICC. The enteric nervous system of the mutant mice appeared normal. From these findings, we conclude that W(jic)/W(jic) mice represent a distinct, novel genotype resulting in a lack of a specific type of ICC in the gastrointestinal musculature. PMID- 21979410 TI - Effects of attractiveness and status in dating desire in homosexual and heterosexual men and women. AB - The present study examined partner preferences of homosexual and heterosexual men and woman, focusing on attractiveness and status. Homosexual (N=591 men; M age=28.87 years, SD=10.21; N=249 women; M age=33.36 years, SD=13.12) and heterosexual participants (N=346 men; M age=39.74 years, SD=14.26; N=400 women; M age=35.93 years, SD=13.72) rated the importance of attractiveness and social status of potential partners and then, in a vignette test, expressed their desire to date hypothetical potential partners based on photographs that varied in attractiveness and status-related profiles. With ratings, heterosexual men valued attractiveness the most, followed by homosexual men, heterosexual women, and homosexual women. Heterosexual women rated social status as most important. When status profiles were manipulated and accompanied with photographs of faces, the pattern of differences between homosexuals and heterosexuals supported the self reported results. Overall, homosexual men and women have similar mate preferences to heterosexual men and women by showing more dating desire for attractive and high social status persons. Compared to attractiveness, status played a smaller role in dating desire. PMID- 21979411 TI - Early high-intensity rehabilitation following total knee arthroplasty improves outcomes. AB - STUDY DESIGN: Prospective cohort study with an age-matched and sex-matched control group. OBJECTIVES: To assess the clinical outcomes of a high-intensity rehabilitation program (HI) compared to those of a group of age-matched and sex matched controls who underwent a lower intensity rehabilitation program. BACKGROUND: Total knee arthroplasty (TKA) successfully alleviates pain from knee osteoarthritis; but deficits in function can persist long term. Despite these well-known deficits, there is little evidence supporting the use of rehabilitation interventions following TKA. METHODS: Eight patients, who participated in the HI program, were compared to 8 age-matched and sex-matched patients who participated in a lower intensity rehabilitation program (control group). Patients were assessed preoperatively, and at 3.5, 6.5, 12, 26, and 52 weeks postoperatively. Assessment of patients included measures of pain, range of motion (ROM), functional performance, and quadriceps strength and activation. RESULTS: There were no differences in knee ROM and pain between the HI and control groups at any postoperative time point. At the 3.5-week and 12-week (end of rehabilitation) time points, the HI group had better functional performance and quadriceps strength compared to the control group (P<.05). At the 52-week time point, the HI group continued to demonstrate better functional performance compared to the control group (P<.05), along with greater quadriceps strength (P = .08). CONCLUSION: A HI program leads to better short- and long-term strength and functional performance outcomes compared to a lower intensity rehabilitation program. The HI program did not impair knee ROM and did not result in any musculoskeletal injuries in this small group of patients. LEVEL OF EVIDENCE: Therapy, level 2b. PMID- 21979412 TI - The standardized extract of Loeselia mexicana possesses anxiolytic activity through the gamma-amino butyric acid mechanism. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Loeselia mexicana (Lam.) Brand has been used in Mexican Traditional Medicine to treat "espanto" or "susto" (fear), which is a culturally affiliated syndrome whose symptomatology comprises loss of appetite, difficulty in sleeping, and also nausea and fatigue, with a sensation of fear or risk - real or imagined - to external stimuli. AIM OF THE STUDY: The anxiolytic effect of the standardized methanol extract of Loeselia mexicana, with regard to its content of coumarin daphnoretin, was researched utilizing the elevated plus maze (EPM) in order to demonstrate whether the biological effect produced by the plant is antagonized by drugs that block gamma-amino butyric acid (GABA)ergic transmission. MATERIALS AND METHODS: The methanolic extract of Loeselia mexicana (LmMeOH) was tested at different doses on the EPM and then the interaction of this extract was evaluated in the same model with different GABAergic drugs, such as flumazenil (FLU) 10mg/kg, bicuculline (BIC) 5mg/kg, pentylenetetrazole (PTZ) 10mg/kg, and picrotoxin (PTX) 2mg/kg. The effect of all of these treatments was evaluated by means of the open field test (OFT). Coumarin content was measured by the high performance liquid chromatography (HPLC) technique. RESULTS: The 200- and 400-mg/kg doses of methanolic extract containing 3.14 and 6.28 mg of daphnoretin, respectively, induced an anxiolytic effect in the EPM without modification of the spontaneous motor activity. The anxiolytic activity of 200mg/kg of methanolic extract in EPM-exposed mice was antagonized by PTX, BIC, and FLU, but not by PTZ. CONCLUSION: The data presented here indicate that the Loeselia mexicana Brand methanolic extract possesses a significant anxiolytic effect that appears to be mediated in part by activation of the GABAergic system. PMID- 21979413 TI - Manipulation of L-ascorbic acid biosynthesis pathways in Solanum lycopersicum: elevated GDP-mannose pyrophosphorylase activity enhances L-ascorbate levels in red fruit. AB - Ascorbate (AsA) plays a fundamental role in redox homeostasis in plants and animals, primarily by scavenging reactive oxygen species. Three genes, representing diverse steps putatively involved in plant AsA biosynthesis pathways, were cloned and independently expressed in Solanum lycopersicum (tomato) under the control of the CaMV 35S promoter. Yeast-derived GDP-mannose pyrophosphorylase (GMPase) and arabinono-1,4-lactone oxidase (ALO), as well as myo-inositol oxygenase 2 (MIOX2) from Arabidopsis thaliana, were targeted. Increases in GMPase activity were concomitant with increased AsA levels of up to 70% in leaves, 50% in green fruit, and 35% in red fruit. Expression of ALO significantly pulled biosynthetic flux towards AsA in leaves and green fruit by up to 54 and 25%, respectively. Changes in AsA content in plants transcribing the MIOX2 gene were inconsistent in different tissue. On the other hand, MIOX activity was strongly correlated with cell wall uronic acid levels, suggesting that MIOX may be a useful tool for the manipulation of cell wall composition. In conclusion, the Smirnoff-Wheeler pathway showed great promise as a target for biotechnological manipulation of ascorbate levels in tomato. PMID- 21979414 TI - Anti-T lymphocyte globulin (ATG) induces generation of regulatory T cells, at least part of them express activated CD44. AB - We show here that the anti-T lymphocyte immunoglobulin (ATG) can induce Treg cells following 24-h incubation in human peripheral blood mononuclear cells (PBMCs). The ATG-induced Treg cells express known cell surface markers (e.g., CD25, FoxP3) and suppress the proliferation of autologous responder PBMCs, stimulated with allogeneic PBMCs, when added into the mixed lymphocyte culture (MLC) at zero time point or 48 h later. We expanded the characteristics of the ATG-induced human Treg cells by showing that they express a novel biomarker designated "activated CD44". ATG-induced Treg cells retain their suppressor function after freezing and thawing or irradiation. Suppression of MLC by ATG induced Treg cells is consistently seen when the Treg cells and the responder cells were derived from the same donor, but not when they derived from different donors. Finally, patients undergoing stem cell transplantation and conditioned with ATG generate in vivo Treg cells that suppress MLC. PMID- 21979416 TI - [Early intervention for allergic rhinitis]. PMID- 21979415 TI - Serum concentrations of cyclooxygenase-2 in patients with systemic sclerosis: association with lower frequency of pulmonary fibrosis. AB - Systemic sclerosis (SSc) is a multisystem disease in which interplay between inflammation, autoimmunity and fibrosis appears to play an indispensable role. Owing to the suggested role of cyclooxygenase-2 enzymes (Cox-2) in inflammation and fibrosis, we investigated their serum concentrations in SSc patients and their clinical and laboratory associations. Serum from 49 patients with SSc, 28 of whom had limited cutaneous SSc (lSSc) and 21 had diffuse cutaneous SSc (dSSc) subtypes, and from 27 healthy subjects were assayed for Cox-2 and TNF by enzyme linked immunosorbent assay (ELISA). Demographic, clinical, autoantibodies and serological data were prospectively assessed. The analysis revealed that patients with lSSc had higher levels of serum Cox-2 than controls. Serum Cox-2 levels were increased in SSc patients with arthritis and digital ulcers; on the contrary, these were diminished in those with associated pulmonary fibrosis. An additional prospective large scale, longitudinal study should be carried out to support these findings and to reveal the mechanistic connections between Cox-2 levels and SSc disease manifestations. PMID- 21979417 TI - [Early intervention for childhood atopic dermatitis: present and future]. PMID- 21979418 TI - [Evidences incorporated to the guidelines for the management of urticaria]. PMID- 21979419 TI - [Clinical evaluation of omega-5 gliadin-specific IgE test]. AB - OBJECTIVE: To reveal the clinical utility of an IgE test specific to omega-5 gliadin in the diagnosis of immediate-type wheat allergy. METHODS: We detected omega-5 gliadin-specific IgE in sera from all patients examined for wheat specific IgE in our allergy clinic between January and October, 2008. The diagnostic value of the test was analyzed against the true diagnosis of wheat allergy based on oral wheat challenge or convincing clinical history. Subjects comprised 233 patients (median age, 3.6 years), 59 patients were diagnosed with wheat allergy, and 174 were judged to have no wheat allergy. RESULTS: The prevalence of being diagnosed as wheat allergy was 68% in the patients with CAP score 2 to omega-5 gliadin IgE (n=31), and 87% in those with CAP score 3 (n=15). All of the 3 patients with CAP score 4 or more were wheat allergic. However, 24% of patients with wheat allergy showed negative results (<0.35 UA/ml). According to the data, we proposed the probability curve of omega-5 gliadin-specific IgE. CONCLUSIONS: IgE testing specific to omega-5 gliadin can offer a useful clinical marker for the diagnosis of immediate-type wheat allergy. But the data should always be evaluated with wheat-specific IgE titers, because of the low clinical sensitivity to detect the patients with wheat allergy. PMID- 21979420 TI - [Effect of weight reduction on respiratory function in obese children with asthma]. AB - BACKGROUND: Though the epidemiological relationship between obesity and asthma has been widely investigated, the mechanism is less known. Several studies have examined that weight loss improved lung function in adults. However, it has not been systematically studied in children. We investigated the effect of weight reduction on respiratory function in obese children with asthma. METHODS: We selected 10 obese children aged 7-13 years with physician diagnosed asthma who was subjected the weight reduction program in Fukuoka National Hospital in 2003 2007. Obesity was defined by BMI >90 percentile of the same age population. Before and after the program, they performed the spirometry. And they were measured the height, the weight, the %Fat, and the Fat volume. Logistic linear analysis was conducted to determine the correlation between relative change in each obesity markers and relative change in each respiratory parameter. RESULTS: Reduction of BMI, %Fat, and Fat volume correlated with relative changes in %FVC and %FEV1. Reduction of %Fat and Fat volume also correlated with relative changes in %PEF and %V50. CONCLUSION: Reduction of BMI, %Fat, and Fat volume can improve respiratory function in obese children with asthma. Obesity may be contribute to aggravate the symptoms of asthma. PMID- 21979421 TI - Cold plasma selectivity and the possibility of a paradigm shift in cancer therapy. AB - BACKGROUND: Plasma is an ionised gas that is typically generated in high temperature laboratory conditions. However, recent progress in atmospheric plasmas has led to the creation of cold plasmas with ion temperature close to room temperature. METHODS: Both in-vitro and in-vivo studies revealed that cold plasmas selectively kill cancer cells. RESULTS: We show that: (a) cold plasma application selectively eradicates cancer cells in vitro without damaging normal cells; and (b) significantly reduces tumour size in vivo. It is shown that reactive oxygen species metabolism and oxidative stress responsive genes are deregulated. CONCLUSION: The development of cold plasma tumour ablation has the potential of shifting the current paradigm of cancer treatment and enabling the transformation of cancer treatment technologies by utilisation of another state of matter. PMID- 21979422 TI - Low ANXA10 expression is associated with disease aggressiveness in bladder cancer. AB - BACKGROUND: Markers for outcome prediction in bladder cancer are urgently needed. We have previously identified a molecular signature for predicting progression in non-muscle-invasive bladder cancer. ANXA10 was one of the markers included in the signature and we now validated the prognostic relevance of ANXA10 at the protein level. METHODS: We investigated ANXA10 expression by immunohistochemistry using a tissue microarray with 249 Ta and T1 urothelial carcinomas. The expression of ANXA10 was also investigated in an additional set of 97 more advanced tumours. The functional role of ANXA10 in cell lines was investigated by siRNA-mediated ANXA10 knockdown using wound-healing assays, proliferation assays, and ingenuity pathway analysis. RESULTS: Low expression of ANXA10 correlated with shorter progression-free survival in patients with stage Ta and T1 tumours (P<0.00001). Furthermore, patients with more advanced tumours and low ANXA10 expression had an unfavourable prognosis (P<0.00001). We found that ANXA10 siRNA transfected cells grew significantly faster compared with control siRNA transfected cells. Furthermore, a wound-healing assay showed that ANXA10 siRNA transfected cells spread along wound edges faster than control transfected cells. CONCLUSION: We conclude that ANXA10 may be a clinical relevant marker for predicting outcome in both early and advanced stages of bladder cancer. PMID- 21979423 TI - Systemically administered PEDF against primary and secondary tumours in a clinically relevant osteosarcoma model. AB - BACKGROUND: Pigment epithelium-derived factor (PEDF) is an endogenous glycoprotein with a potential role as a therapeutic for osteosarcoma. Animal studies have demonstrated the biological effects of PEDF on osteosarcoma; however, these results are difficult to extrapolate for human use due to the chosen study design and drug delivery methods. METHODS: In this study we have attempted to replicate the human presentation and treatment of osteosarcoma using a murine orthotopic model of osteosarcoma. The effects of PEDF on osteosarcoma cell lines were evaluated in vitro prior to animal experimentation. Orthotopic tumours were induced by intra-tibial injection of SaOS-2 osteosarcoma cells. Treatment with PEDF was delayed until after the macroscopic appearance of primary tumours. Pigment epithelium-derived factor was administered systemically via an implanted intraperitoneal micro-osmotic pump. RESULTS: In vitro, PEDF inhibited proliferation, induced apoptosis and inhibited cell cycling of osteosarcoma cells. Pigment epithelium-derived factor promoted adhesion to Collagen I and inhibited invasion through Collagen I. In vivo, treatment with PEDF caused a reduction in both primary tumour volume and burden of pulmonary metastases. Systemic administration of PEDF did not cause toxic effects on normal tissues. CONCLUSION: Systemically delivered PEDF is effective in suppressing the size of primary and secondary tumours in an orthotopic murine model of osteosarcoma. PMID- 21979424 TI - Methamphetamine-induced vascular changes lead to striatal hypoxia and dopamine reduction. AB - Methamphetamine (meth) is a potent psychostimulant known to cause neurotoxicity. Clinical reports suggest meth abuse is a risk factor for Parkinson's disease. We investigated changes in the blood-brain barrier and cerebral vasculature as a mechanism underlying this risk in rats treated acutely and trained to self administer meth. We observed blood-brain barrier leakage in rats treated acutely with meth. Hypoperfusion in the striatum was detected with acute and chronic meth treatment and was associated with hypoxia. This was correlated with reductions in striatal tyrosine hydroxylase in rats trained to self-administer meth. These findings suggest a new mechanism of meth-induced neurotoxicity involving striatal vasoconstriction resulting in hypoxia and dopamine reductions leading to an increased risk for Parkinson's disease for meth abusers. PMID- 21979425 TI - Site-specific subtypes of macrophages recruited after peripheral nerve injury. AB - After partial ligation of mouse sciatic nerve, the subtypes of macrophages were examined in the injured nerve and dorsal root ganglia (DRGs). Many M1 macrophages, which were inducible nitric oxide synthase (iNOS)-positive and arginase-1 (Arg-1)-negative, and neutrophils infiltrated the injured nerve. In contrast, almost all macrophages infiltrating the ipsilateral side of DRGs after the nerve injury were iNOS-/Arg-1+, M2 type. The infiltration of M1 and M2 macrophages was first observed in the injured nerve and ipsilateral DRGs on days 1 and 2, respectively. In addition, the macrophage infiltration preceded the activation of microglia in the ipsilateral dorsal horn of spinal cord. Thus, infiltrating macrophages after peripheral nerve injury may play unique roles dependent on the location in the development of neuropathic pain. PMID- 21979426 TI - Linker-mediated assembly of gold nanoparticles into multimeric motifs. AB - We present a theoretical description of linker-mediated self-assembly of gold nanoparticles (Au-NP). Using mesoscale simulations with a coarse-grained model for the Au NPs and dirhenium-based linker molecules, we investigate the conditions under which large clusters can grow and construct a phase diagram that identifies favorable growth conditions in terms of floating and bound linker concentrations. The findings can be considered as generic, as we expect other NP linker systems to behave in a qualitatively similar way. In particular, we also discuss the case of antibody-functionalised Au NPs connected by the C-reactive proteins (CRPs). We extract some general rules for NP linking that may aid the production of size- and shape-specific NP clusters for technology applications. PMID- 21979428 TI - Thermoset polyester droplet-based microfluidic devices for high frequency generation. AB - The vast majority of droplet-based microfluidic devices are made from polydimethylsiloxane (PDMS). Unfortunately PDMS is not suitable for high frequency droplet generation at high operating pressure due to its low shear modulus. In this paper, we report the fabrication and testing of microfluidic devices using thermoset polyester (TPE). The optical characteristics of the fabricated devices were assessed and substrate resistance to pressure also investigated. TPE devices bonded using an O(2) plasma treated PET substrate at 76 degrees C were shown to function efficiently at pressures up to 18 MPa. TPE material retains many of the attractive features of PDMS such as ease of fabrication but significantly, has superior mechanical properties. The improved resistance of TPE to high pressures enabled investigation of high frequency droplet generation as a function of a wide range of flow-rates with three different oils as continuous phase. PMID- 21979427 TI - Reconstruction and 3D visualisation based on objective real 3D based documentation. AB - Reconstructions based directly upon forensic evidence alone are called primary information. Historically this consists of documentation of findings by verbal protocols, photographs and other visual means. Currently modern imaging techniques such as 3D surface scanning and radiological methods (computer tomography, magnetic resonance imaging) are also applied. Secondary interpretation is based on facts and the examiner's experience. Usually such reconstructive expertises are given in written form, and are often enhanced by sketches. However, narrative interpretations can, especially in complex courses of action, be difficult to present and can be misunderstood. In this report we demonstrate the use of graphic reconstruction of secondary interpretation with supporting pictorial evidence, applying digital visualisation (using 'Poser') or scientific animation (using '3D Studio Max', 'Maya') and present methods of clearly distinguishing between factual documentation and examiners' interpretation based on three cases. The first case involved a pedestrian who was initially struck by a car on a motorway and was then run over by a second car. The second case involved a suicidal gunshot to the head with a rifle, in which the trigger was pushed with a rod. The third case dealt with a collision between two motorcycles. Pictorial reconstruction of the secondary interpretation of these cases has several advantages. The images enable an immediate overview, give rise to enhanced clarity, and compel the examiner to look at all details if he or she is to create a complete image. PMID- 21979429 TI - Histamine reverses a memory deficit induced in rats by early postnatal maternal deprivation. AB - Early partial maternal deprivation causes long-lasting neurochemical, behavioral and brain structural effects. In rats, it causes a deficit in memory consolidation visible in adult life. Some of these deficits can be reversed by donepezil and galantamine, which suggests that they may result from an impairment of brain cholinergic transmission. One such deficit, representative of all others, is an impairment of memory consolidation, clearly observable in a one trial inhibitory avoidance task. Recent data suggest a role of brain histaminergic systems in the regulation of behavior, particularly inhibitory avoidance learning. Here we investigate whether histamine itself, its analog SKF 91844, or various receptor-selective histamine agonists and antagonists given into the CA1 region of the hippocampus immediately post-training can affect retention of one-trial inhibitory avoidance in rats submitted to early postnatal maternal deprivation. We found that histamine, SKF-91844 and the H2 receptor agonist, dimaprit enhance consolidation on their own and reverse the consolidation deficit induced by maternal deprivation. The enhancing effect of histamine was blocked by the H2 receptor antagonist, ranitidine, but not by the H1 receptor antagonist pyrilamine or by the H3 antagonist thioperamide given into CA1 at doses known to have other behavioral actions, without altering locomotor and exploratory activity or the anxiety state of the animals. The present results suggest that the memory deficit induced by early postnatal maternal deprivation in rats may in part be due to an impairment of histamine mediated mechanisms in the CA1 region of the rat hippocampus. PMID- 21979430 TI - Qualifying the use of RIS data for patient dose by comparison with DICOM header data. AB - A system was developed in 2008 to calculate patient doses using Radiology Information System (RIS) data and presents these data as a patient dose audit. One of the issues with this system was the quality of user-entered data. It has been shown that Digital Imaging and Communication in Medicine (DICOM) header data can be used to perform dose audits with a high level of data accuracy. This study aims to show that using RIS data for dose audits is not only a viable alternative to using DICOM header data, but that it has advantages. A new system was developed to pull header data from DICOM images easily and was installed on a workstation within a hospital department. Data were recovered for a common set of examinations using both RIS and DICOM header data. The data were compared on a result-by-result basis to check for consistency of common fields between RIS and DICOM, as well as assessing the value of data fields uncommon to both systems. The study shows that whilst RIS is not as accurate as DICOM, it does provide enough accurate data and that it has other advantages over using a DICOM approach. These results suggest that a 'best of both worlds' may be achievable using Modality Performed Procedure Step (MPPS). PMID- 21979431 TI - Health physics aspects in treatment rooms after 18-MV X-ray irradiations. AB - Delayed activation products contribute to the exposure of the staff operating high-energy accelerators. Induced activity was studied in a treatment room following 18-MV X-ray irradiations using a hand-held system that allows both dose rate measurements and spectroscopic analysis. The major activation products and the corresponding nuclear reactions were identified. At the majority of the studied locations, beta(+) emitters were the main short-term dose contributors. The time variation of the absorbed dose rate in a treatment room during the first 20-min post-irradiation was represented by the sum of two exponential components with half-lives of 1-2 min and either 4 or 10 min, depending on the location in the room. Components with a half-life of hours or days contribute <1 % to the initial dose rate. The activation of some accessories, such as iron filters and portal imagers, deserve special attention. The collection of such data with the proposed method allows the development of optimised working protocols at each treatment room. PMID- 21979432 TI - Clinical audit: Development of the criteria of good practices. AB - Clinical audit is a systematic review of the procedures in order to improve the quality and the outcome of patient care, whereby the procedures are examined against agreed standards for good medical RADIOLOGICAL procedures. The criteria of good procedures (i.e. the good practice) are thus the cornerstones for development of clinical audits: these should be the basis of assessments regardless of the type of the audit--external, internal, comprehensive or partial. A lot of criteria for good practices are available through the recommendations and publications by international and national professional societies and other relevant organisations. For practical use in clinical audits, the criteria need to be compiled, sorted out and agreed on for the particular aims of an audit (comprehensive or partial, external or internal). The national professional and scientific societies can provide valuable contribution to this development. For examination--or treatment-specific criteria--preliminary consensus needs to be obtained with the help of clinical experts, while clinical audits can be useful as a benchmarking tool to improve the criteria. PMID- 21979433 TI - The beta-chain of cell surface F(0)F(1) ATPase modulates apoA-I and HDL transcytosis through aortic endothelial cells. AB - OBJECTIVE: Both HDLs and their major protein constituent apolipoprotein A-I (apoA I) are transported through aortic endothelial cells. The knock-down of the ATP binding cassette transporters A1 (ABCA1), G1 (ABCG1), and of the scavenger receptor-BI (SR-BI) diminishes but does not completely block the transport of apoA-I or HDL, so that other receptors appear to be involved. The ectopic beta chain of F(0)F(1) ATPase has been previously characterized as an apoA-I receptor, triggering HDL internalization in hepatocytes. METHODS AND RESULTS: The ectopic presence of the beta-chain of F(0)F(1) ATPase on the surface of endothelial cells was confirmed by cell surface biotinylation. RNA-interference and the F(0)F(1) ATPase inhibitory peptide IF(1) reduced cell binding of apoA-I but not HDL, as well as association and transendothelial transport of both apoA-I and HDL. Furthermore, apoA-I stimulated F(0)F(1) ATPase catalyzed ATP hydrolysis. The generated ADP as well as apoA-I stimulated the binding, cell association, and internalization of HDL. Both in the presence and absence of ADP inhibition of the purinergic receptor P2Y(12) but not P2Y(1) decreased the cell association of apoA I and HDL. Coinhibition of beta-ATPase and ABCA1 had no additive effects on the cell association and transport of apoA-I. Reduced cell association of HDL by beta ATPase inhibition was not further decreased by additional knock-down of ABCG1 or SR-BI. CONCLUSIONS: Binding of apoA-I to ectopic F(0)F(1) ATPase triggers the generation of ADP, which via activation of the purinergic receptor P2Y(12) stimulates the uptake and transport of HDL and initially lipid-free apoA-I by endothelial cells. PMID- 21979434 TI - Macrophage polarization by angiotensin II-type 1 receptor aggravates renal injury acceleration of atherosclerosis. AB - OBJECTIVE: Angiotensin II is a major determinant of atherosclerosis. Although macrophages are the most abundant cells in atherosclerotic plaques and express angiotensin II type 1 receptor (AT1), the pathophysiologic role of macrophage AT1 in atherogenesis remains uncertain. We examined the contribution of macrophage AT1 to accelerated atherosclerosis in an angiotensin II-responsive setting induced by uninephrectomy (UNx). METHODS AND RESULTS: AT1(-/-) or AT1(+/+) marrow from apolipoprotein E deficient (apoE(-/-)) mice was transplanted into recipient apoE(-/-) mice with subsequent UNx or sham operation: apoE(-/-)/AT1(+/+)->apoE(-/ )+sham; apoE(-/-)/AT1(+/+) ->apoE(-/-)+UNx; apoE(-/-)/AT1(-/-)->apoE(-/-)+sham; apoE(-/-)/AT1(-/-)->apoE(-/-)+UNx. No differences in body weight, blood pressure, lipid profile, and serum creatinine were observed between the 2 UNx groups. ApoE( /-)/AT1(+/+) ->apoE(-/-)+UNx had significantly more atherosclerosis (16907+/ 21473 versus 116071+/-8180 MUm(2), P<0.05). By contrast, loss of macrophage AT1 which reduced local AT1 expression, prevented any effect of UNx on atherosclerosis (77174+/-9947 versus 75714+/-11333 MUm(2), P=NS). Although UNx did not affect total macrophage content in the atheroma, lesions in apoE(-/ )/AT1(-/-)->apoE(-/-)+UNx had fewer classically activated macrophage phenotype (M1) and more alternatively activated phenotype (M2). Further, UNx did not affect plaque necrosis or apoptosis in apoE(-/-)/AT1(-/-)->apoE(-/-) whereas it significantly increased both (by 2- and 6-fold, respectively) in apoE(-/ )/AT1(+/+) ->apoE(-/-) mice. Instead, apoE(-/-)/AT1(-/-)->apoE(-/-) had 5-fold increase in macrophage-associated apoptotic bodies, indicating enhanced efferocytosis. In vitro studies confirmed blunted susceptibility to apoptosis, especially in M2 macrophages, and a more efficient phagocytic function of AT1(-/ ) macrophages versus AT1(+/+). CONCLUSIONS: AT1 receptor of bone marrow-derived macrophages worsens the extent and complexity of renal injury-induced atherosclerosis by shifting the macrophage phenotype to more M1 and less M2 through mechanisms that include increased apoptosis and impaired efferocytosis. PMID- 21979435 TI - Transforming growth factor-beta signaling in myogenic cells regulates vascular morphogenesis, differentiation, and matrix synthesis. AB - OBJECTIVE: Transforming growth factor-beta (TGF-beta) signaling is required for normal vascular development. We aimed to discover the role of TGF-beta signaling in embryonic smooth muscle cells (SMCs). METHODS AND RESULTS: We bred mice with smooth muscle (SM) 22alpha-Cre and Tgfbr2(flox) alleles to generate embryos in which the type II TGF-beta receptor (TGFBR2; required for TGF-beta signaling) was deleted in SMCs. Embryos were harvested between embryonic day (E) 9.5 and E18.5 and examined grossly, microscopically, and by histochemical and RNA analyses. SM22alpha-Cre(+/0) Tgfbr2(flox/flox) (knockout [KO]) embryos died before E15.5 with defects that included cardiac outflow tract abnormalities, persistence of the right dorsal aorta, and dilation of the distal aorta. Histological analyses suggested normal expression of SMC differentiation markers in KO aortas; however, RNA analyses showed that SMC differentiation markers were increased in KO cardiac outflow vessels but decreased in the descending aorta. KO aortas had only rare mature elastin deposits and contained abnormal aggregates of extracellular matrix proteins. Expression of several matrix proteins was significantly decreased in KO descending aortas but not in cardiac outflow vessels. CONCLUSIONS: TGF-beta signaling in SMCs controls differentiation, matrix synthesis, and vascular morphogenesis. Effects of TGF-beta on SMC gene expression appear to differ depending on the location of SMCs in the aorta. PMID- 21979436 TI - Heparin strongly induces soluble fms-like tyrosine kinase 1 release in vivo and in vitro--brief report. AB - OBJECTIVE: Soluble fms-like tyrosine kinase 1 (sFlt1) is involved in the pathophysiology of preeclampsia and coronary artery disease. Because sFlt1 has a heparin-binding site, we investigated whether or not heparin releases sFlt1 from the extracellular matrix. METHODS AND RESULTS: We measured sFlt1 before and after heparin administration in 135 patients undergoing coronary angiography, percutanous coronary intervention, or both. sFlt1 was increased directly after heparin administration (from 254 to 13,440 pg/mL) and returned to baseline within 10 hours. Umbilical veins and endothelial cells treated with heparin released sFlt1. Heparinase I and III also increased sFlt1. Mice treated with heparin had elevated sFlt1 serum levels. Their serum inhibited endothelial tube formation. CONCLUSIONS: Heparin releases sFlt1 by displacing the sFlt1 heparin-binding site from heparan sulfate proteoglycans. Heparin could induce an antiangiogenic state. PMID- 21979437 TI - Abcc6 deficiency causes increased infarct size and apoptosis in a mouse cardiac ischemia-reperfusion model. AB - OBJECTIVE: ABCC6 genetic deficiency underlies pseudoxanthoma elasticum (PXE) in humans, characterized by ectopic calcification, and early cardiac disease. The spectrum of PXE has been noted in Abcc6-deficient mice, including dystrophic cardiac calcification. We tested the role of Abcc6 in response to cardiac ischemia-reperfusion (I/R) injury. METHODS AND RESULTS: To determine the role of Abcc6 in cardioprotection, we induced ischemic injury in mice in vivo by occluding the left anterior descending artery (30 minutes) followed by reperfusion (48 hours). Infarct size was increased in Abcc6-deficient mice compared with wild-type controls. Additionally, an Abcc6 transgene significantly reduced infarct size on the background of a naturally occurring Abcc6 deficiency. There were no differences in cardiac calcification following I/R, but increased cardiac apoptosis was noted in Abcc6-deficient mice. Previous studies have implicated the bone morphogenetic protein (BMP) signaling pathway in directing calcification, and here we showed that the BMP responsive transcription factors pSmad1/5/8 were increased in hearts of Abcc6 mice. Consistent with this finding, BMP4 and BMP9 were increased and activin receptor-like kinase-2 and endoglin were downregulated in cardiac extracts from Abcc6-deficient mice versus controls. CONCLUSIONS: These data identify Abcc6 as a novel modulator of cardiac myocyte survival after I/R. This cardioprotective mechanism may involve inhibition of the BMP signaling pathway, which modulates apoptosis. PMID- 21979439 TI - Comparison of diffusion coefficients for matched pairs of macrocyclic and linear molecules over a drug-like molecular weight range. AB - The diffusion coefficients of a series of closely matched pairs of macrocyclic and linear molecules have been compared using NMR spectroscopy. The macrocyclic series was designed both to overlap with and extend beyond the molecular weight range typically employed for drug-like molecules. The linear molecules each represent a carbogenic fission of their macrocyclic counterparts, designed to minimize differences in functionality and physicochemical properties. Each series of molecules was prepared using copper catalyzed azide-alkyne cycloaddition (CuAAC) reactions conducted in a flow using a copper tube. The macrocyclic series exhibited consistently higher diffusion across the entire molecular weight range studied. The fold difference in diffusion coefficients between the macrocyclic and linear analogues appeared to be independent of either solvent viscosity or dielectric environment. PMID- 21979438 TI - Spatial distribution and mechanical function of elastin in resistance arteries: a role in bearing longitudinal stress. AB - OBJECTIVE: Despite the role that extracellular matrix (ECM) plays in vascular signaling, little is known of the complex structural arrangement between specific ECM proteins and vascular smooth muscle cells. Our objective was to examine the hypothesis that adventitial elastin fibers are dominant in vessels subject to longitudinal stretch. METHODS AND RESULTS: Cremaster muscle arterioles were isolated, allowed to develop spontaneous tone, and compared with small cerebral arteries. 3D confocal microscopy was used to visualize ECM within the vessel wall. Pressurized arterioles were fixed and stained with Alexa 633 hydrazide (as a nonselective ECM marker), anti-elastin, or anti-type 1 collagen antibody and a fluorescent nuclear stain. Exposure of cremaster muscle arterioles to elastase for 5 minutes caused an irreversible lengthening of the vessel segment that was not observed in cerebral arteries. Longitudinal elastin fibers were demonstrated on cremaster muscle arterioles using 3D imaging but were confirmed to be absent in cerebral vessels. The fibers were also distinct from type I collagen fibers and were degraded by elastase treatment. CONCLUSIONS: These results indicate the importance of elastin in bearing longitudinal stress in the arteriolar wall and that these fibers constrain vascular smooth muscle cells. Differences between skeletal muscle and cerebral small arteries may reflect differences in the local mechanical environment, such as exposure to longitudinal stretch. PMID- 21979440 TI - The effect of glucose dose and fasting interval on cognitive function: a double blind, placebo-controlled, six-way crossover study. AB - RATIONALE: Previous research has identified a number of factors that appear to moderate the behavioural response to glucose administration. These include physiological state, dose, types of cognitive tasks used and level of cognitive demand. Another potential moderating factor is the length of the fasting interval prior to a glucose load. OBJECTIVES: Therefore, we aimed to examine the effect of glucose dose and fasting interval on mood and cognitive function. METHODS: The current study utilised a double-blind, placebo-controlled, balanced, six period crossover design to examine potential interactions between length of fasting interval (2 versus 12 hours) and optimal dose for cognition enhancement. RESULTS: Results demonstrated that the higher dose (60 g) increased working memory performance following an overnight fast, whereas the lower dose (25 g) enhanced working memory performance following a 2-h fast. CONCLUSIONS: The data suggest that optimal glucose dosage may differ under different conditions of depleted blood glucose resources. In addition, glucoregulation was observed to be a moderating factor. However, further research is needed to develop a model of the moderating and mediating factors under which glucose facilitation is best achieved. PMID- 21979442 TI - Efficacy of long-acting moxidectin against sarcoptic mange in naturally infested sheep. PMID- 21979441 TI - Effects of alpha-2A adrenergic receptor agonist on time and risk preference in primates. AB - RATIONALE: Subjective values of actions are influenced by the uncertainty and immediacy of expected rewards. Multiple brain areas, including the prefrontal cortex and basal ganglia, are implicated in selecting actions according to their subjective values. Alterations in these neural circuits, therefore, might contribute to symptoms of impulsive choice behaviors in disorders such as substance abuse and attention-deficit hyperactivity disorder (ADHD). In particular, the alpha-2A noradrenergic system is known to have a key influence on prefrontal cortical circuits, and medications that stimulate this receptor are currently in use for the treatment of ADHD. OBJECTIVE: We tested whether the preference of rhesus monkeys for delayed and uncertain reward is influenced by the alpha-2A adrenergic receptor agonist, guanfacine. METHODS: In each trial, the animal chose between a small, certain and immediate reward and another larger, more delayed reward. In half of the trials, the larger reward was certain, whereas in the remaining trials, the larger reward was uncertain. RESULTS: Guanfacine increased the tendency for the animal to choose the larger and more delayed reward only when it was certain. By applying an econometric model to the animal's choice behavior, we found that guanfacine selectively reduced the animal's time preference, increasing their choice of delayed, larger rewards, without significantly affecting their risk preference. CONCLUSIONS: In combination with previous findings that guanfacine improves the efficiency of working memory and other prefrontal functions, these results suggest that impulsive choice behaviors may also be ameliorated by strengthening prefrontal functions. PMID- 21979443 TI - In vitro activity of rifaximin against Chlamydia suis. PMID- 21979444 TI - Co-stimulatory molecules in and beyond co-stimulation - tipping the balance in atherosclerosis? AB - A plethora of basic laboratory and clinical studies has uncovered the chronic inflammatory nature of atherosclerosis. The adaptive immune system with its front runner, the T cell, drives the atherogenic process at all stages. T cell function is dependent on and controlled by a variety of either co-stimulatory or co inhibitory signals. In addition, many of these proteins enfold T cell-independent pro-atherogenic functions on a variety of cell types. Accordingly they represent potential targets for immune-modulatory and/or anti-inflammatory therapy of atherosclerosis. This review focuses on the diverse role of co-stimulatory molecules of the B7 and tumour necrosis factor (TNF)-superfamily and their downstream signalling effectors in atherosclerosis. In particular, the contribution of CD28/CD80/CD86/CTLA4, ICOS/ICOSL, PD-1/PDL-1/2, TRAF, CD40/CD154, OX40/OX40L, CD137/CD137L, CD70/CD27, GITR/GITRL, and LIGHT to arterial disease is reviewed. Finally, the potential for a therapeutic exploitation of these molecules in the treatment of atherosclerosis is discussed. PMID- 21979445 TI - Health-related quality of life in women with fibromyalgia: clinical and psychological factors associated. AB - The objective of the study was to analyse the impact of fibromyalgia (FM) on health-related quality of life (HRQOL) and to identify clinical and psychological factors associated with the disease. A cross-sectional study was conducted with adult Portuguese women with FM. Analysed data were demographic, clinical and psychological variables and HRQOL: SF-36 and Fibromyalgia Impact Questionnaire (FIQ). The relationship between HRQOL and the other variables was made with a bivariate analysis. To assess the relative contribution of clinical and psychological variables, a series of multiple regression analyses were designed and made. The study sample consisted of 76 women with FM (49.61 +/- 10.07 years). All dimensions of HRQOL were affected in FM, especially Physical Functioning, Physical Role Functioning and General Health. The mean FIQ total score was 68.59 +/- 17.54, and 40 patients (53%) presented scores >=70. Pain intensity, assessed by a 10-cm visual analogue scale (VAS), was a significant predictor of HRQOL in expressing association with FIQ and all dimensions of SF-36, except Emotional Role Functioning. Anxiety (Hospital Anxiety and Depression Scale (HADS)) was a significant predictor of the Mental Component and General Health (SF-36). Depression (HADS) was related with Vitality, Mental Health and FIQ. Emotion focused coping was related with General Health and Emotional Role Functioning, and social support (Satisfaction with Social Support Scale (ESSS)) was related with the Social Functioning. These clinical and psychological variables explained an acceptable proportion of variability (R (2)), ranging from 31.3% on Emotional Role Functioning to 70.6% on FIQ, except for Physical Role Functioning (R (2) = 6.1). FM has a negative impact on both general and specific dimensions of HRQOL, especially the physical dimensions. Pain intensity, anxiety and depression symptoms and the emotion-focused coping are the most relevant explanatory variables of the impact of FM on HRQOL. PMID- 21979446 TI - The diagnostic value of the proposal for clinical gout diagnosis (CGD). AB - The purpose of this study is to determine the diagnostic properties of the clinical gout diagnosis (CGD) proposal in patients with gout and other rheumatic diseases. We investigated the presence of current or past history of the previously published CGD criteria: (1) >1 attack of acute arthritis, (2) mono/oligoarthritis attacks, (3) rapid progression of pain and swelling (<24 h), (4) podagra, (5) erythema, (6) unilateral tarsitis, (7) probable tophi, and (8) hyperuricemia. CGD was established in patients with greater than or equal to four out of eight of these criteria. Demographic data and comorbidities were also considered. Statistical analysis included diagnostic test evaluation (sensitivity, specificity, likelihood ratios, positive predictive values and receiving operating characteristic curves). One hundred and sixty-seven patients with the following diagnoses were included: gout (most in intercritical period, n = 75), rheumatoid arthritis (RA, n = 30), osteoarthritis (OA, n = 31) and spondyloarthritis (SpA, n = 31). All gout patients had MSU crystal demonstration and constituted the gold standard for diagnostic test evaluation. There were significant differences across diagnostic groups in most demographic variables and comorbidity. The presence of greater than or equal to four out of eight of the CGD criteria were found in 97% patients with gout, in two patients with SpA, and one each with RA and OA. The sensitivity, specificity, and LR+ of greater than or equal to four out of eight of the CGD criteria were 97.3%, 95.6%, and 22.14, respectively. The presence of more than or equal to four out of eight items from the CGD proposal is highly suggestive of gout. PMID- 21979447 TI - Mission impossible? Mission possible? PMID- 21979448 TI - Who needs ACL surgery? An open question. PMID- 21979450 TI - Identification of a novel mutation within the goat adiponectin gene and its effect on body weight in Chinese indigenous breeds. PMID- 21979452 TI - Medical, psychological and socioeconomic aspects of aging in Poland: assumptions and objectives of the PolSenior project. AB - Both descriptive and longitudinal studies of aging are nowadays a subject of growing interest in different countries worldwide. However, in Poland and other Central-Eastern European countries, such comprehensive, nationally representative, multidimensional studies were never performed in the past in elderly population. The present paper describes the PolSenior project including its objectives, sample selection and structure, methods, fieldwork procedures and study flow. The aim of the project was to examine medical, psychological and socioeconomic aspects of aging in Poland. The research sample included 5695 respondents (2899 males and 2796 females) split into six equally sized age groups of elderly individuals (65-69 years, 70-74 years, 75-79 years, 80-84 years, 85-89 years, 90+years) and one group of subjects just about to enter old age (55-59 years). Subjects were recruited using three stage stratified, proportional draw. The response rate was 42% and ranged from 32% to 61% between provinces. The study consisted of three visits performed by trained nurses including questionnaire survey, comprehensive geriatric assessment and blood and urine sampling. The questionnaire consisted of medical and specific socioeconomic questions. The comprehensive geriatric assessment included blood pressure and anthropometric measurements, as well as selected scales and tests routinely used in the examination of elderly subjects. Blood and urine samples were collected from 4737 and 4526 individuals, respectively. More than 50 biochemical parameters were measured, and DNA was isolated and banked. In a selected group of 1018 subjects, a medical examination by a physician was performed. The self-rated health was lower in females than in males in age groups 70-84, but similar in individuals of both sexes aged 65-69 and 85 years. Besides providing data on health and functioning of elderly population, the PolSenior project aims to analyze interrelationships between different elements of health and social status, and between genetics and health status in advanced age. The results of the PolSenior project will facilitate prioritizing the state's public health and social policies in elderly population. Such a program provides also an excellent starting point for longitudinal studies and a basis for comparative analysis between Poland and other European countries or regions. PMID- 21979453 TI - Development of a method for detecting Coxiella burnetii in cheese samples. AB - Coxiella burnetii is the causative agent of Q fever, and the main route of infection in humans is inhalation of contaminated aerosols. Although oral transmission by contaminated raw milk or dairy products is also a possible route of human infection, there have been few studies investigating the presence of C. burnetii in dairy products. We developed a new method of extracting DNA from cheese and detecting C. burnetii DNA in cheese samples with a nested PCR assay. The limit of detection was 6.0 * 10(2) C. burnetii particles per gram. We subsequently used this method to examine the presence of C. burnetii in cheese at commercial markets in Tokyo from June 2005 to December 2008. Twenty-eight of 147 cheese samples were found to be positive for C. burnetii DNA. However, when we assessed the viability of C. burnetii by inoculating mice with DNA-positive samples, all of the samples were found to be negative. Thus, the viability of C. burnetii appears to have been lost in these cheese samples. PMID- 21979451 TI - Comparison of the effects of acute and chronic administration of ketamine on hippocampal oscillations: relevance for the NMDA receptor hypofunction model of schizophrenia. AB - The proper organization and function of GABAergic interneuron networks is essential for many cognitive processes and abnormalities in these systems have been documented in schizophrenic patients. The memory function of the hippocampus depends on two major patterns of oscillations in the theta and gamma ranges, both requiring the intact functioning of the network of fast-firing interneurons expressing parvalbumin. We examined the ability of acute and chronic administration of NMDA receptor (NMDA-R) antagonists to recapitulate the oscillatory dysfunctions observed in schizophrenia. In freely moving rats, acute injection of MK801 or ketamine increased gamma power in both CA1 and dentate gyrus of the hippocampus. Theta peak shifted to higher frequencies whereas the average 5-10 Hz theta power decreased by 24% in CA1 and remained high in the dentate gyrus. Strong increase in CA1 gamma and decrease in theta power triggered by brainstem stimulation were found under urethane anesthesia. In contrast to acute experiments, chronic administration of ketamine caused a steady decline in both gamma and theta oscillations, 2-4 weeks after treatment. A further important difference between the two models was that the effects of acute injection were more robust than the changes after chronic treatment. Chronic administration of ketamine also leads to decrease in the number of detectable parvalbumin interneurons. Histological examination of interindividual differences indicated, however, that within the ketamine treated group a further decrease in parvalbumin neurons correlated with strengthening of oscillations. The findings are consistent with abnormalities of oscillations in human schizophrenia and further validate the NMDA-R hypofunction hypothesis. PMID- 21979454 TI - Indices using external measurements for assessing fat deposition of adult feral raccoons (Procyon lotor) in Kanagawa Prefecture, Japan. AB - We examined the use of external measurements and relative fat deposition of adult feral raccoons (Procyon lotor) to develop relative indices of body fat deposition in post-growth feral raccoons. From March 2006 to March 2010, 288 adult raccoon carcasses (110 males, 178 females) collected in Kanagawa Prefecture, Japan, which were determined to be 24 months old, were subjected to external measurements of body weight (BW), girth measurement (GM), and body mass index (BMI). To assess relative body fat deposition, we visually classified abdominal subcutaneous fat into three grades (Visible Fat Index [VFI]: I-III). Significant differences in the means of BW (both sexes:P<0.01), GM (females: P<0.05, males: P<0.01), and BMI (both sexes: P<0.01) were detected between seasons. Notably, the means of BW, GM, and BMI (all, both sexes: P<0.01) differed significantly between VFI grades. However, by discriminant analysis with BW, GM, and BMI as independent variables, we obtained a significant discriminant function (both sexes: P<0.01) for distinguishing VFI I from higher VFI grades, but no significant equation was obtained for distinguishing between VFI II and VFI III. Based on the obtained structure matrix of discriminant analysis, BMI was the most valuable component for the discrimination of VFI grades. Thus, we conclude that BMI is a suitable complementary index for assessing relative body fat deposition of adult feral raccoons in Kanagawa Prefecture and may be generalizable to populations in other areas. PMID- 21979455 TI - Experimental hyperlipemia induces insulin resistance in cats. AB - The effect of experimental hyperlipemia on insulin sensitivity was evaluated in seven healthy cats. Serum triglyceride and free fatty acid concentrations were significantly (P<0.05) higher when lipid-heparin was administered (2,894 +/- 1,526 mg/dl and 4.54 +/- 0.70 mEq/l, respectively) than when saline was administered (70 +/- 42 mg/dl and 0.22 +/- 0.08 mEq/l, respectively). A glucose clamp test revealed that the mean glucose infusion rate when lipid-heparin was administered (5.80 +/- 0.67 mg/kg/min) was significantly (P<0.05) lower than when saline was administered (8.52 +/- 1.83 mg/kg/min). These results suggest that experimental hyperlipemia induced insulin resistance in the healthy cats. PMID- 21979456 TI - Development of a multiplex PCR and PCR-RFLP method for serotyping of Avibacterium paragallinarum. AB - Avibacterium (Haemophilus) paragallinarum (A. paragallinarum) is a causative agent of infectious coryza in chickens and is classified into three serovars by agglutination tests. In an effort to identify the serovars easily, PCR and PCR RFLP were employed. As the target gene for PCR, the hypervariable region of HMTp210, which encodes the HA antigen, was used. PCR using primer sets around the hypervariable region amplified 0.8, 1.1 and 1.6 kbp fragments for serovars A, B and C, respectively. Alternatively, the 1.6 kbp fragments were amplified with another primer pair encompassing the hypervariable region and was subjected to digestion with Bgl II, which resulted in the detection of serovar-specific digestion patterns. These results indicate that PCR and PCR-RFLP using the hypervariable region of HMTp210 are alternative methods to identify the serovar of A. paragallinarum. PMID- 21979457 TI - Prevalence of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in food-producing animals. AB - To evaluate the diversity of extended-spectrum beta-lactamases (ESBL) genes among food-producing animals, 48 isolates of ESBL-producing Escherichia coli isolates were obtained from rectal samples of broilers, layers, beef cattle and pigs, at the slaughterhouse level. ESBL-carrying E. coli were isolated from 60.0% of individual broiler rectal samples, 5.9% of layers, 12.5% of beef cattle and 3% of pigs. One ESBL-producing Klebsiella pneumoniae was isolated from a broiler. The ESBL-positive E. coli isolates from broilers harbored various ESBL genes: bla (SHV-12), bla(CTX-M-2), bla(CTX-M-14), bla(CTX-M-15) and bla(CTX-M-44). The plasmid DNAs were analyzed by restriction patterns. Homogeneous band patterns were yielded in those of K. pneumoniae and E. coli isolates harboring the bla(CTX M-2) gene from different farms. No genetic relation between the 2 CTX-M-14 ESBL producing strains was found by pulsed-field gel electrophoresis, although 2 plasmids in these strains, obtained from different broiler farms, were similar to each other. This study provides evidence that the proliferation of CTX-M producing E. coli is due to the growth of indigenous CTX-M-producing strains and the possible emergence of strains that acquired CTX-M genes by horizontal transfer in different broiler farms. CTX-M-producing coliforms in broilers should be controlled due to the critical importance of cephalosporins and the zoonotic potential of ESBL-producing bacteria. PMID- 21979458 TI - Laparoscopic compared with robotic sacrocolpopexy for vaginal prolapse: a randomized controlled trial. AB - OBJECTIVE: To compare conventional laparoscopic and robotic-assisted laparoscopic sacrocolpopexy for vaginal apex prolapse. METHODS: This single-center, blinded randomized trial included participants with stage 2-4 posthysterectomy vaginal prolapse. Participants were randomized to laparoscopic or robotic sacrocolpopexy. The primary outcome was total operative time from incision to closure. Secondary outcomes were postoperative pain, functional activity, bowel and bladder symptoms, quality of life, anatomic vaginal support, and cost from a health care system perspective. RESULTS: A total of 78 patients enrolled and were randomized (laparoscopic n=38; robotic n=40). Total operative time was significantly longer in the robotic group compared with the laparoscopic group (+67-minute difference; 95% confidence interval [CI] 43-89; P<.001). Anesthesia time, total time in the operating room, total sacrocolpopexy time, and total suturing time were all significantly longer in the robotic group. Participants in the robotic group also had significantly higher pain at rest and with activity during weeks 3 through 5 after surgery and required longer use of nonsteroidal anti-inflammatory drugs (median, 20 compared with 11 days, P<.005). The robotic group incurred greater cost than the laparoscopic group (mean difference +$1,936; 95% CI $417-$3,454; P=.008). Both groups demonstrated significant improvement in vaginal support and functional outcomes 1 year after surgery with no differences between groups. CONCLUSION: Robotic-assisted sacrocolpopexy results in longer operating time and increased pain and cost compared with the conventional laparoscopic approach. PMID- 21979459 TI - Delayed postpartum preeclampsia and eclampsia: demographics, clinical course, and complications. AB - OBJECTIVE: To estimate and evaluate the demographics, clinical course, and complications of delayed postpartum preeclampsia in patients with and without eclampsia. METHODS: We conducted a retrospective cohort study of patients who were discharged and later readmitted with the diagnosis of delayed postpartum preeclampsia more than 2 days to 6 weeks or less after delivery between January 2003 and August 2009. RESULTS: One hundred fifty-two patients met criteria for the diagnosis of delayed postpartum preeclampsia. Of these, 96 (63.2%) patients had no antecedent diagnosis of hypertensive disease in the current pregnancy, whereas seven (4.6%), 14 (9.2%), 28 (18.4%), and seven (4.6%) patients had gestational hypertension, chronic hypertension, preeclampsia, and preeclampsia superimposed on chronic hypertension, respectively, during the peripartum period. Twenty-two patients (14.5%) developed postpartum eclampsia, and more than 90% of these patients presented within 7 days after discharge from the hospital. The most common presenting symptom was headache in 105 (69.1%) patients. Patients who developed eclampsia were significantly younger than those who did not (mean +/- standard deviation, 23.2 +/- 6.2 compared with 28.3 +/- 6.7 years; adjusted odds ratio [OR] 1.13, 95% confidence interval [CI] 1.02-1.26, P=.03), and other demographic variables were no different. A lower readmission hemoglobin was associated with a lower odds of progression to eclampsia (10.7 +/- 1.7 compared with 11.6 +/- 2.2 g/dL, adjusted OR 0.75, 95% CI 0.57-0.98, P=.04). CONCLUSION: One week after discharge appears to be a critical period for the development of postpartum eclampsia. Education about the possibility of delayed postpartum preeclampsia and eclampsia should occur after delivery, whether or not patients develop hypertensive disease before discharge from the hospital. PMID- 21979460 TI - Effect of AZO seed layer on electrochemical growth and optical properties of ZnO nanorod arrays on ITO glass. AB - We report the structural and optical properties of ZnO nanorod arrays (NRAs) grown by an electrochemical deposition process. The ZnO NRAs were grown on indium tin oxide (ITO) coated glass substrates with a thin sputtered Al-doped ZnO (AZO) seed layer and compared with ones directly grown without the seed layer. The growth condition dependence of ZnO NRAs was investigated for various synthetic parameters. The morphology and density of the ZnO NRAs were accordingly controlled by means of zinc nitrate concentration and growth time. From photoluminescence results, the ultraviolet emission was significantly enhanced after thermal treatment. For ZnO NRAs grown on ITO glass without the seed layer, the diffuse transmittance was enhanced despite the reduction in the total transmittance, indicating a high haze value. By using a thin AZO seed layer, the well-aligned ZnO NRAs on AZO/ITO glass are controllably and reproducibly synthesized by varying the growth parameters, exhibiting a total transmittance higher than 91% in the visible wavelength range as well as good optical and crystal quality. PMID- 21979462 TI - Efficient approach to novel 1alpha-triazolyl-5alpha-androstane derivatives as potent antiproliferative agents. AB - Stereoselective 1,4-Michael addition of azoimide to 17beta-acetoxy-5alpha-adrost 1-en-3-one was carried out to furnish a 1alpha-azido-3-ketone, which was reduced to give the 3beta- and 3alpha-hydroxy epimers in a ratio of 5 : 2. The Cu(I) catalyzed 1,3-dipolar cycloaddition of the major isomer to terminal alkynes afforded 1alpha-triazolyl derivatives, which were deacetylated to the corresponding 3beta,17beta-diols or oxidized to the analogous 3-ketones. However, the ability of the minor 1alpha,3alpha-azidoalcohol to undergo similar cyclization was found to be affected significantly by the steric bulk of the substituents on the alkyne reaction partner. All triazolyl compounds were tested in vitro on three malignant gynecological cell lines (HeLa, MCF7 and A2780). PMID- 21979463 TI - Implications of transvascular fluid exchange in nonlinear, biphasic analyses of flow-controlled infusion in brain. AB - A nonlinear, coupled biphasic-mass transport model that includes transvascular fluid exchange is proposed for flow-controlled infusions in brain tissue. The model accounts for geometric and material nonlinearities, a hydraulic conductivity dependent on deformation, and transvascular fluid exchange according to Starling's law. The governing equations were implemented in a custom-written code assuming spherical symmetry and using an updated Lagrangian finite-element algorithm. Results of the model indicate that, using normal physiological values of vascular permeability, transvascular fluid exchange has negligible effects on tissue deformation, fluid pressure, and transport of the infused agent. As vascular permeability may be increased artificially through methods such as administering nitric oxide, a parametric study was conducted to determine how increased vascular permeability affects flow-controlled infusion. Increased vascular permeability reduced both tissue deformation and fluid pressure, possibly reducing damage to tissue adjacent to the infusion catheter. Furthermore, the loss of fluid to the vasculature resulted in a significantly increased interstitial fluid concentration but a modestly increased tissue concentration. From a clinical point of view, this increase in concentration could be beneficial if limited to levels below which toxicity would not occur. However, the modestly increased tissue concentration may make the increase in interstitial fluid concentration difficult to assess in vivo using co-infused radiolabeled agents. PMID- 21979461 TI - Understanding the structural ensembles of a highly extended disordered protein. AB - Developing a comprehensive description of the equilibrium structural ensembles for intrinsically disordered proteins (IDPs) is essential to understanding their function. The p53 transactivation domain (p53TAD) is an IDP that interacts with multiple protein partners and contains numerous phosphorylation sites. Multiple techniques were used to investigate the equilibrium structural ensemble of p53TAD in its native and chemically unfolded states. The results from these experiments show that the native state of p53TAD has dimensions similar to a classical random coil while the chemically unfolded state is more extended. To investigate the molecular properties responsible for this behavior, a novel algorithm that generates diverse and unbiased structural ensembles of IDPs was developed. This algorithm was used to generate a large pool of plausible p53TAD structures that were reweighted to identify a subset of structures with the best fit to small angle X-ray scattering data. High weight structures in the native state ensemble show features that are localized to protein binding sites and regions with high proline content. The features localized to the protein binding sites are mostly eliminated in the chemically unfolded ensemble; while, the regions with high proline content remain relatively unaffected. Data from NMR experiments support these results, showing that residues from the protein binding sites experience larger environmental changes upon unfolding by urea than regions with high proline content. This behavior is consistent with the urea-induced exposure of nonpolar and aromatic side-chains in the protein binding sites that are partially excluded from solvent in the native state ensemble. PMID- 21979464 TI - TRAP1 and the proteasome regulatory particle TBP7/Rpt3 interact in the endoplasmic reticulum and control cellular ubiquitination of specific mitochondrial proteins. AB - Tumor necrosis factor receptor-associated protein-1 (TRAP1) is a mitochondrial (MITO) antiapoptotic heat-shock protein. The information available on the TRAP1 pathway describes just a few well-characterized functions of this protein in mitochondria. However, our group's use of mass-spectrometric analysis identified TBP7, an AAA-ATPase of the 19S proteasomal subunit, as a putative TRAP1 interacting protein. Surprisingly, TRAP1 and TBP7 colocalize in the endoplasmic reticulum (ER), as demonstrated by biochemical and confocal/electron microscopic analyses, and interact directly, as confirmed by fluorescence resonance energy transfer analysis. This is the first demonstration of TRAP1's presence in this cellular compartment. TRAP1 silencing by short-hairpin RNAs, in cells exposed to thapsigargin-induced ER stress, correlates with upregulation of BiP/Grp78, thus suggesting a role of TRAP1 in the refolding of damaged proteins and in ER stress protection. Consistently, TRAP1 and/or TBP7 interference enhanced stress-induced cell death and increased intracellular protein ubiquitination. These experiments led us to hypothesize an involvement of TRAP1 in protein quality control for mistargeted/misfolded mitochondria-destined proteins, through interaction with the regulatory proteasome protein TBP7. Remarkably, expression of specific MITO proteins decreased upon TRAP1 interference as a consequence of increased ubiquitination. The proposed TRAP1 network has an impact in vivo, as it is conserved in human colorectal cancers, is controlled by ER-localized TRAP1 interacting with TBP7 and provides a novel model of the ER-mitochondria crosstalk. PMID- 21979465 TI - FADD cleavage by NK cell granzyme M enhances its self-association to facilitate procaspase-8 recruitment for auto-processing leading to caspase cascade. AB - Granzyme M (GzmM), an orphan Gzm, is constitutively and abundantly expressed in innate effector natural killer cells. We previously demonstrated that GzmM induces caspase (casp)-dependent apoptosis and cytochrome c release from mitochondria. We also resolved the crystal structure for GzmM and generated its specific inhibitor. However, how GzmM causes casp activation has not been defined. Here we found that casp-8 is an initiator caspase in GzmM-induced casp cascade, which causes other casp activation and Bid cleavage. GzmM does not directly cleave procaspase-3 and Bid, whose processing is casp dependent. Casp-8 knockdown or deficient cells attenuate or abolish GzmM-induced proteolysis of procaspase-3 and Bid. Extrinsic death receptor pathway adaptor Fas-associated protein with death domain (FADD) contributes to GzmM-induced casp-8 activation. GzmM specifically cleaves FADD after Met 196 to generate truncated FADD (tFADD) that enhances its self-association for oligomerization. The oligomerized tFADD facilitates procaspase-8 recruitment to promote its auto-processing leading to casp activation cascade. FADD-deficient cells abrogate GzmM-induced activation of casp-8 and apoptosis as well as significantly inhibit lymphokine-activated killer cell-mediated cytotoxicity. FADD processing by GzmM can potentiate killing efficacy against tumor cells and intracellular pathogens. PMID- 21979466 TI - Terminally differentiated astrocytes lack DNA damage response signaling and are radioresistant but retain DNA repair proficiency. AB - The impact and consequences of damage generation into genomic DNA, especially in the form of DNA double-strand breaks, and of the DNA-damage response (DDR) pathways that are promptly activated, have been elucidated in great detail. Most of this research, however, has been performed on proliferating, often cancerous, cell lines. In a mammalian body, the majority of cells are terminally differentiated (TD), and derives from a small pool of self-renewing somatic stem cells. Here, we comparatively studied DDR signaling and radiosensitivity in neural stem cells (NSC) and their TD-descendants, astrocytes - the predominant cells in the mammalian brain. Astrocytes have important roles in brain physiology, development and plasticity. We discovered that NSC activate canonical DDR upon exposure to ionizing radiation. Strikingly, astrocytes proved radioresistant, lacked functional DDR signaling, with key DDR genes such as ATM being repressed at the transcriptional level. Nevertheless, astrocytes retain the expression of non-homologous end-joining (NHEJ) genes and indeed they are DNA repair proficient. Unlike in NSC, in astrocytes DNA-PK seems to be the PI3K-like protein kinase responsible for gammaH2AX signal generation upon DNA damage. We also demonstrate the lack of functional DDR signaling activation in vivo in astrocytes of irradiated adult mouse brains, although adjacent neurons activate the DDR. PMID- 21979467 TI - MiR-181 mediates cell differentiation by interrupting the Lin28 and let-7 feedback circuit. AB - MicroRNAs (miRNAs) have attracted attention because of their key regulatory functions in many biological events, including differentiation and tumorigenesis. Recent studies have reported the existence of a reciprocal regulatory loop between the family of let-7 miRNAs and an RNA-binding protein, Lin28, both of which have been documented for their important roles during cell differentiation. Hence, using bipotent K562 human leukemia cells and human CD34+ hematopoietic progenitor cells as research models, we demonstrate that let-7 and Lin28 have contrary roles in megakaryocytic (MK) differentiation with a dynamic balance; expression of miR-181 is capable of effectively repressing Lin28 expression, disrupting the Lin28-let-7 reciprocal regulatory loop, upregulating let-7, and eventually promoting MK differentiation. However, miR-181 lacks a significant effect on hemin-induced erythrocyte differentiation. These results demonstrate that miR-181 can function as a 'molecular switch' during hematopoietic lineage progression specific to MK differentiation, thus providing insight into future development of miRNA-oriented therapeutics. PMID- 21979469 TI - Colorectal cancer screening in Hong Kong: investment of more resources needed to strengthen screening services and inform governmental policy. PMID- 21979468 TI - Inflammatory synovial fluid microenvironment drives primary human chondrocytes to actively take part in inflammatory joint diseases. AB - The role of human chondrocytes in the pathogenesis of cartilage degradation in rheumatic joint diseases has presently gained increasing interest. An active chondrocyte participation in local inflammation may play a role in the initiation and progression of inflammatory joint diseases and in a disruption of cartilage repair mechanisms resulting in cartilage degradation. In the present study, we hypothesized that inflammatory synovial fluid triggers human chondrocytes to actively take part in inflammatory processes in rheumatic joint diseases. Primary human chondrocytes were incubated in synovial fluids gained from patients with rheumatoid arthritis, psoriasis arthritis and reactive arthritis. The detection of vital cell numbers was determined by using Casy Cell Counter System. Apoptosis was measured by Annexin-V and 7AAD staining. Cytokine and chemokine secretion was determined by a multiplex suspension array. Detection of vital cells showed a highly significant decrease in chondrocyte numbers. Flow cytometry demonstrated a significant increase in apoptotic chondrocytes after the incubation. An active secretion of cytokines such as MCP-1 and MIF by chondrocytes was observed. The inflammatory synovial fluid microenvironment mediates apoptosis and cell death of chondrocytes. Moreover, in terms of cytokine secretion, it also induces an active participation of chondrocytes in ongoing inflammation. PMID- 21979470 TI - Faecal occult blood screening: knowledge, attitudes, and practice in four Hong Kong primary care clinics. AB - OBJECTIVES. To assess primary care patients for their awareness, knowledge, and attitude towards colorectal cancer and screening, to report on the uptake of faecal occult blood test screening and the results of screening, and explore predictors of screening uptake. DESIGN. Cross-sectional study. SETTING. Four primary care clinics in Hong Kong. PATIENTS. A total of 1664 patients aged 50 to 74 years attending the clinics in the period July 2006 to July 2007. MAIN OUTCOME MEASURES. Percentage of subjects who were aware that colorectal cancer is common and curable at an early stage, and who knew that faecal occult blood test or colonoscopy is useful for screening; relevant knowledge score; uptake rate of faecal occult blood testing; rate of testing positive; and factors predicting uptake. RESULTS. A total of 1645 questionnaires were collected. In all, 89% (95% confidence interval, 88-91%) were aware that colorectal cancer is common, 95% (94 96%) believed faecal occult blood test and colonoscopy are useful for screening, and 58% (56-61%) achieved a knowledge score of 50% or above. The uptake rate of the faecal occult blood test was 35%. Uptake was higher among those with a positive family history (odds ratio=1.57; 95% confidence interval, 1.08-2.27; P=0.02), those who were more aware that colorectal cancer is common (1.86; 1.29 2.69; P=0.001), and that colorectal cancer is potentially curable at an early stage (1.76; 1.32-2.36; P=0.0001). Rate of testing positive was 2.1% (95% confidence interval, 0.9-3.3%); no colorectal cancer was detected and the neoplasia detection rate (for cancers and adenomas) was 5.1 per 1000 subjects screened. CONCLUSIONS. Patients were aware that colorectal cancer is common in our community, and faecal occult blood test or colonoscopy is useful for screening. The uptake of screening was low, though relatively higher for those with a positive family history and greater awareness of the high frequency and potential for cure of colorectal cancer. Faecal occult blood test positivity rate was 2.1%, and neoplasia detection rate 5.1 per 1000 screened. PMID- 21979471 TI - Colorectal cancer surgery of octogenarians in Hong Kong: who will survive? AB - OBJECTIVE. To assess the accuracy of the Association of Coloproctology of Great Britain and Ireland scoring system in predicting the 30-day mortality after surgery for colorectal cancer in Hong Kong elderly (aged 80 years or more) patients. DESIGN. Early mortality outcome audit in a historical cohort. SETTING. Queen Elizabeth Hospital, Hong Kong. PATIENTS. All Chinese patients (aged 80 years or more) who underwent elective or emergency surgery for colorectal cancer in the Department of Surgery between January 2005 and December 2009. MAIN OUTCOME MEASURES. Receiver operating characteristic curve analyses were used to estimate the predictive ability of the score. RESULTS. In all, 180 patients with colorectal cancer were included in this review. The overall 30-day and hospital mortality rates were 29/180 (16%) and 31/180 (17%), respectively. The Association of Coloproctology of Great Britain and Ireland score was significantly higher among patients who died within 30 days (4.2 vs 3.1, P=0.0001), and was the only independent predictor for 30-day mortality by logistic regression (P=0.009; odds ratio=2.555; 95% confidence interval, 1.277-4.932). The mean score of this study population was 3.22 (median, 3.10), giving a predicted 30-day mortality rate of 16.0 to 17.4%, which corresponded with an observed 30-day mortality of 16.1% encountered in this study. The score had a significantly larger area under the curve for the 30-day mortality rates (odds ratio=0.811; 95% confidence interval, 0.722-0.849) as compared to the American Society of Anesthesiologists score (0.664; 0.589-0.735) [P=0.0001]. CONCLUSION. The Association of Coloproctology of Great Britain and Ireland scoring system can accurately predict the 30-day mortality rate of elderly Hong Kong Chinese patients (aged 80 years or more) operated on for colorectal cancer. PMID- 21979472 TI - Use of nutritional health supplements and associated factors among parents with children at kindergartens in Hong Kong. AB - OBJECTIVES. To estimate the prevalence of so-called nutritional health supplement consumption among kindergarten children; secondarily to explore potential factors associated with such consumption. DESIGN. Cross-sectional, self-administered questionnaire survey. SETTING. One kindergarten each in Hong Kong island, Kowloon, and the New Territories region. SUBJECTS. Parents who had a child studying at the three sampled kindergartens in April 2010. RESULTS. Of 951 sets of parents, 730 (77%) responded. Approximately 52% (95% confidence interval, 47 58%) of the respondents gave regular health supplements to their child. The commonest type of supplement given was cod fish oil (69%). Approximately 36% of the respondents did not know the upper limit dosage of their supplement. Parents of only 66% of regular health supplements consumers, compared to 75% of non regular users, knew that there was an inherent risk from over-consumption (P=0.018). Parental beliefs that "It is useful/important for normal child development" (adjusted odds ratio=1.93; 95% confidence interval, 1.18-3.16; P=0.009), "It is useful/important for immune function" (1.79; 1.05-3.05; P=0.032) were associated with consumption of health such supplements. CONCLUSION. There is high rate of health supplement consumption among healthy kindergarten children in Hong Kong. There are wrong beliefs from parents that health supplements are important for normal-growing children for their normal growth and body immunity. About one-third of parents has limited knowledge on potential side-effects of overdose and do not know the limit of consumption. Education on "Less (health supplement) is more (health)" is recommended. PMID- 21979473 TI - Trigger thumbs in children: results of surgical release. AB - OBJECTIVE. To evaluate results from surgical release of trigger thumbs in children in a regional hospital cluster in Hong Kong. DESIGN. Descriptive case series. SETTING. A regional hospital cluster, Hong Kong. PATIENTS. Data from 1993 to 2009 on 180 children with 209 trigger thumbs were collected. Analyses into gender, predominance of thumb, age of onset, associated abnormalities and family history, symptoms and signs, surgical outcomes, and postoperative complications were carried out retrospectively. RESULTS. There were 92 girls and 88 boys having trigger thumbs (1.05:1). In all, 29 (16%) of the children presented with bilateral trigger thumbs, while the right thumb was singly involved in 81 (45%) and the left thumb in 70 (39%) of the children. The mean age of onset was 19 months; only 20% were diagnosed before the age of 1 year. Only nine (5%) of the children were associated with congenital diseases and none had a positive family history of trigger thumb. Flexion deformity was the major presenting feature, other than triggering or pain. A nodule and flexion deformity were very commonly observed during physical examination. More than 95% of the operated thumbs with transverse incision acquired a good range of movement with a scarcely apparent scar. A residual flexion deformity was evident in only 4%, mostly in children who underwent surgical release under the age of 1 year. CONCLUSION. Surgical release is recommended for children with trigger thumbs aged more than 1 year, which attains satisfactory results with minimal complications. PMID- 21979474 TI - Prospective evaluation of seropositive occult hepatitis B viral infection in lymphoma patients receiving chemotherapy. AB - OBJECTIVE. To serially evaluate the viral kinetics of occult hepatitis B virus infection in lymphoma patients and perform a correlation with clinical outcomes. DESIGN. Case series with 1-year follow-up. SETTING. Regional hospital, Hong Kong. PATIENTS. Consecutive patients who were newly diagnosed to have lymphoma in the hospital between 1 April 2007 and 31 March 2008 were tested for hepatitis B (HB) surface (s) antigen (Ag), anti-HBs antibody (Ab) and anti-HB core (c) Ab. Seropositive occult hepatitis B patients as defined by being negative for HBsAg but positive anti-HBsAb and/or anti-HBcAb without a hepatitis B vaccination history were recruited. Serum HBsAg, anti-HBsAb, anti-HBcAb, hepatitis B virus deoxyribonucleic acid (DNA) level, and liver biochemistry were checked at baseline and every 4 weeks during and after chemotherapy until 12 months after the completion of chemotherapy or death. Entecavir was started if patients developed biochemical flare-up of hepatitis B associated with virological rebound. The prevalence and course of hepatitis B virus-related hepatitis, as well as any temporal relationship to viral kinetics and clinical hepatitis, were assessed. RESULTS. Of 47 patients tested, 10 (21%) with lymphoma were seropositive occult hepatitis carriers. Their median baseline hepatitis B virus DNA level was 89 IU/mL (range, <34-807 IU/mL). Virological rebound (as defined by a 10-fold increase in serum hepatitis B virus DNA level from pre-chemotherapy level persisted for 4 weeks) occurred in one of the 10 patients, followed by biochemical reactivation. Whereupon entecavir treatment was started and no liver failure ensued. Regarding the other seropositive occult patients, their serum hepatitis B virus DNA levels fluctuated, but there was no associated biochemical reactivation. CONCLUSION. Detectable baseline serum hepatitis B virus DNA is not uncommon in patients with occult hepatitis B who receive chemotherapy. Transient elevation in serum hepatitis B virus DNA levels does not predict biochemical reactivation, but antiviral treatment might be considered if virological rebound persists. PMID- 21979475 TI - Centipede bite victims: a review of patients presenting to two emergency departments in Hong Kong. AB - OBJECTIVE. To review the clinical characteristics of patients presenting after centipede bites in Hong Kong. DESIGN. Descriptive case series. SETTING. Emergency departments of two public hospitals in Hong Kong. PATIENTS. Patients presenting after centipede bites between 2006 and 2010. MAIN OUTCOME MEASURES. Demographics, time and locations of bites, symptoms and signs, treatments and outcomes. RESULTS. A total of 46 relevant patient records were retrieved. The bites were frequently at night, indoors, on lower limbs, and consistently resulted in pain. The majority of the victims were treated with analgesia, anti-histamines, and antibiotics. One patient developed necrosis and five re-attended for delayed pruritus and relapsed/recurrent swelling. CONCLUSIONS. Centipede bites are usually uncomplicated, but may lead to necrosis or delayed hypersensitive reactions. PMID- 21979476 TI - Initial experience of cryoballoon catheter ablation for atrial fibrillation in Hong Kong. AB - OBJECTIVE. To report the initial experience in using cryoballoon catheter ablation in the treatment of atrial fibrillation in Hong Kong. DESIGN. Single centre, prospective case series. SETTING. Regional hospital, Hong Kong. PATIENTS. Sixteen patients (mean age, 55 years; standard deviation, 14 years; 11 males) with paroxysmal (n=12) or persistent (n=4) atrial fibrillation. INTERVENTIONS. Pulmonary vein isolation by ablation with a 28-mm cryoballoon catheter. MAIN OUTCOME MEASURES. Safety, effectiveness, and learning curve of this procedure. RESULTS. Of 67 pulmonary veins, 61 (91%) could be successfully isolated with the cryoballoon alone. The remaining pulmonary veins were isolated with additional ablation using an 8-mm tip cryocatheter. One phrenic nerve palsy developed during right middle pulmonary vein ablation, which resolved. Another patient endured a minor guidewire dissection of the right inferior pulmonary vein. The mean (standard deviation) procedural and fluoroscopic times were 231 (32) and 62 (18) minutes, respectively. On comparing the first nine and last seven procedures, there was a significant improvement in procedural time (mean [standard deviation], 244 [32] vs 213 [24] minutes; P=0.04) and in the fluoroscopic time (70 [21] vs 51 [7] minutes; P=0.038). With a median follow-up of 21 months, nine (75%) of the 12 patients with paroxysmal atrial fibrillation and one (25%) of those four with persistent atrial fibrillation had no recurrence, without the use of anti-arrhythmic drugs. CONCLUSIONS. Pulmonary vein isolation by cryoballoon catheter ablation is safe and effective in treating patients with paroxysmal, but not for patients with persistent atrial fibrillation. A relatively short learning curve of around 10 cases was deemed appropriate. PMID- 21979477 TI - Menstrual disorders in a Paediatric and Adolescent Gynaecology Clinic: patient presentations and longitudinal outcomes. AB - OBJECTIVE. To study the presentations, diagnoses, and outcomes in adolescents with menstrual disorders. DESIGN. Prospective cohort study. SETTING. Paediatric and Adolescent Gynaecology Clinic, Hong Kong. PARTICIPANTS. A total of 577 adolescents aged 14 to 19 years. MAIN OUTCOME MEASURES. The presentations and diagnoses of adolescents with menstrual disorders were reviewed and their menstrual outcomes determined by a telephone survey. RESULTS. In all, 47% presented with menorrhagia, prolonged menstruation, and short menstrual cycles; 27% had secondary amenorrhoea, 12% had dysmenorrhoea, 11% had oligomenorrhoea, and 3% had primary amenorrhoea. Significant diagnoses included congenital genital tract anomalies, premature ovarian failure, anorexia nervosa, and polycystic ovarian syndrome. Polycystic ovarian syndrome was diagnosed in 16% of the cohort. In all, 24% of these 577 patients had abnormal menstrual cycles 4 years later. Direct logistic regression analysis indicated a cycle length of more than 35 days at presentation (adjusted odds ratio=2.8; 95% confidence interval, 1.8-4.5), previous diagnosis of polycystic ovarian syndrome (adjusted odds ratio=2.0; 95% confidence interval, 1.1-3.4), and current body mass index of 23 kg/m(2) or higher (adjusted odds ratio=1.8; 95% confidence interval, 1.0-3.0) were risk factors for persistently long menstrual cycle exceeding 35 days. Adolescents who were screened out with a definitive diagnosis after initial assessment were at low risk of persistently long menstrual cycles at follow-up (adjusted odds ratio=0.3; 95% confidence interval, 0.1-0.8). CONCLUSIONS. Adolescent menstrual disorders should not be ignored. Long cycle, diagnosis of polycystic ovarian syndrome at first consultation, and a current body mass index of 23 kg/m(2) or higher were statistically associated with persistent problems. PMID- 21979479 TI - Workshop 2--General approach to critical appraisal of a medical journal paper. PMID- 21979478 TI - Pipeline embolisation device for wide-necked internal carotid artery aneurysms in a hospital in Hong Kong: preliminary experience. AB - OBJECTIVE. To review our hospital's experience with the pipeline embolisation device to reconstruct wide-necked intracranial aneurysms. DESIGN. Descriptive case series. SETTING. A regional neurosurgical centre in Hong Kong. PATIENTS. Patients presented with wide-necked intracranial internal carotid artery aneurysms who underwent pipeline embolisation device reconstruction between October 2008 and June 2009. RESULTS. There were 13 wide-necked internal carotid artery aneurysms (in nine patients) treated by pipeline embolisation device reconstruction. Eleven aneurysms were de-novo; two were recurrent. The complete occlusion rate was 66% (8/13) at the first angiographic follow-up and 69% (9/13) at the second follow-up. One patient developed in-stent stenosis and in another there was distal migration of the stent. There was no added neurological deficit in any patient. CONCLUSION. In our series, the clinical results from using the pipeline embolisation device for the treatment of non-ruptured internal carotid artery aneurysms appeared encouraging. However, larger studies with longer follow up duration are warranted to assess the complications and durability of the device for reconstructing internal carotid artery aneurysms. PMID- 21979480 TI - Severe community-acquired pneumonia caused by macrolide-resistant Mycoplasma pneumoniae in a 6-year-old boy. AB - Mycoplasma pneumoniae is the commonest agent causing atypical pneumonia in children. Macrolides have long been used in the treatment of community-acquired pneumonia not responsive to beta-lactams alone. In this report, we describe the first locally acquired paediatric patient with severe community-acquired pneumonia caused by macrolide-resistant Mycoplasma pneumoniae, possessing an A-to G transition at position 2063 of the 23s rRNA gene. In addition, we have detected two more strains of macrolide-resistant Mycoplasma pneumoniae out of a total of 10 cases with chest infection that were confirmed by polymerase chain reaction. Therefore macrolide-resistant Mycoplasma pneumoniae accounted for 33% (3 out of 10 patients) of the polymerase chain reaction-confirmed cases. PMID- 21979481 TI - Hyperammonaemic encephalopathy in an adult patient with citrin deficiency associated with a novel mutation. AB - We report on an adult patient with citrin deficiency in Hong Kong, in whom a novel mutation was identified. The patient presented with recurrent hyperammonaemic encephalopathy due to impairment of the liver urea cycle enzyme argininosuccinate synthetase. This autosomal recessive condition is also characterised by interesting food preferences, notably aversion to carbohydrates and craving for protein-rich and/or lipid-rich foods, as well as neuropsychiatric symptoms. Plasma amino acid analysis is very useful in revealing urea cycle disorders, and mutational analysis of the SLC25A13 gene can confirm the diagnosis. PMID- 21979482 TI - Calcific tendinitis of the supraspinatus tendon in a 7-year-old boy: diagnostic challenges. AB - This report is of a case of acute calcific tendinitis of supraspinatus tendon in a 7-year-old boy who presented to the hospital with an acute painful shoulder after a fall. Initial radiographs mimicked fracture of the greater tuberosity of the humerus. Subsequent investigation confirmed that the appearance was due to a calcific tendinitis. The patient recovered shortly afterwards with complete resolution of the calcific lesion. PMID- 21979483 TI - Sacrococcygeal teratoma in adults: case report and literature review. AB - Sacrococcygeal teratoma is one of the most common tumours in infants but rare in adults. We present a case of sacrococcygeal teratoma in a female adult. The clinical presentation, radiological and histological findings, management, and outcome are described. PMID- 21979484 TI - Ultrasonography diagnosis of renal arterial thrombosis: an important cause of renal allograft loss in children. PMID- 21979485 TI - An unexpected finding in a lucky elderly man. PMID- 21979486 TI - Malpractice claims: prevention is often a better strategy. PMID- 21979487 TI - Chi squared test versus Fisher's exact test. PMID- 21979488 TI - Chinese translation of primary glioblastoma. PMID- 21979489 TI - Assessing the reliability of the Gambling Functional Assessment: Revised. AB - Dixon and Johnson (Anal Gambl Behav 1: 44-49, 2007) proposed the Gambling Functional Assessment as a tool to identify the consequences maintaining the respondent's gambling behavior, but subsequent studies on its psychometric properties suggested that it could use improvement. The present study investigated the internal consistency of the Gambling Functional Assessment- Revised using the responses of 1,060 undergraduate students. Temporal reliability was assessed by a second administration of the measure four (n = 87) or twelve (n = 98) weeks after the first administration. Temporal reliability was also compared to the South Oaks Gambling Screen (Lesieur and Blume in Am J Psychiatry 144: 1184-1188, 1987), which was also administered at both time points. Internal consistency measures were good to excellent, even when potential non-gamblers were excluded from the analyses. Temporal stability was also very good, with the possible exception of the consequence of "escape" at 12 weeks. The Gambling Functional Assessment--Revised represents a potentially useful tool for researchers and therapists interested in why respondents are gambling. PMID- 21979490 TI - Fermentation RS3 derived from sago and rice starch with Clostridium butyricum BCC B2571 or Eubacterium rectale DSM 17629. AB - Resistant starch type 3 (RS3) is retrograded starch which is not digested by human starch degrading enzyme, and will thus undergo bacterial degradation in the colon. The main fermentation products are the Short Chain Fatty Acid (SCFA): acetate, propionate and butyrate. SCFA has significant benefit impact on the metabolism of the host. The objectives of this research were to study the SCFA profile produced by colonic butyrate producing bacteria grown in medium containing RS3. RS3 was made from sago or rice starch treated with amylase, pullulanase and the combination of amylase and pullulanase. Fermentation study was performed by using Clostridium butyricum BCC B2571 or Eubacterium rectale DSM 17629, which has been identified as capable of degradation of starch residue and also regarded as beneficial bacteria. Experimental result revealed that enzyme hydrolysis of retrograded sago or rice starch was beneficial to RS formation. RS3 derived from sago contained higher RS (31-38%) than those derived from rice starch (21-26%). This study indicated that C. butyricum BCC B2571 produced acetate, propionate and butyrate at molar ratio of 1.8 : 1 : 1, when the medium was supplemented with RSSA at concentration 1%. In the medium containing similar substrate, E. rectale DSM 17629 produced acetate, propionate and butyrate at molar ratio of 1.7 : 1 : 1.2. High levels of acetate, propionate and butyrate at molar ratio of 1.8 : 1 : 1.1 was also produced by E. rectale DSM 17629 in medium supplemented with RSSP at concentration 1%. The results showed that both bacteria responded differently to the RS3 supplementation. Such result provided insight into the possibility of designing RS3 as prebiotic with featured regarding SCFA released in the human colon with potential health implication. PMID- 21979491 TI - The impact of perinatal probiotic intervention on gut microbiota: double-blind placebo-controlled trials in Finland and Germany. AB - Specific probiotic combinations during early feeding, via the mother or incorporated in early formula-feeding, mold the intestinal microbiota composition in infants. The objective was to analyze the impact of probiotic administration to mother or infant on gut microbiota composition in 6-month-old Finnish and German infants. In Finland probiotics were given to mothers (n = 79) for 2 months prior to and 2 months after delivery. In Germany probiotics were started in infants (n = 81) at weaning, at the latest at 1 month of age, and continued for 4 months. A breast-fed group of 6-month-old infants (22 from Finland, 8 from Germany) were compared. Gut microbiota were analyzed by FCM-FISH and qPCR methods. In breast-fed infants a trend toward higher counts of bifidobacteria was detected in Finland (p = 0.097) as against Germany, where a more diverse microbiota was reflected in higher Akkermansia (p = 0.003), Clostridium histolyticum (p = 0.035) and Bacteroides-Prevotella (p = 0.027) levels and a higher percentage of Akkermansia (p = 0.004). Finnish LPR + BL999 intervention group (Lactobacillus rhamnosus LPR and Bifidobacterium longum BL999) had higher percentages of fecal Lactobacillus-Enterococcus (9.0% vs. 6.1% placebo, p = 0.003) and lower bifidobacteria levels (10.03 log cells/g vs. 10.68 log cells/g placebo, p = 0.018). Probiotic treatment had different impacts on gut microbiota composition in Finnish and German infants due to differences in mode of feeding and the early commensal microbiota. Probiotic treatment had different impacts on gut microbiota composition in Finnish and German infants due to differences in mode of feeding and the basic commensal microbiota. PMID- 21979492 TI - Immediate and midterm results following treatment of unruptured intracranial aneurysms with the pipeline embolization device. AB - BACKGROUND AND PURPOSE: A number of flow-diverting devices have become available for endovascular occlusion of cerebral aneurysms. This article reports immediate and midterm results in treating unruptured aneurysms with the PED. MATERIALS AND METHODS: A prospective registry was established at 3 Australian neurointerventional units. Aneurysms were treated on the basis of unfavorable anatomy or recurrence following previous treatment. Aneurysms were treated with PED or PED and coils. Data including antiplatelet therapy, technical issues, complications, and imaging findings were recorded during at least a 6-month period. RESULTS: A total of 57 aneurysms in 54 patients were treated by 5 neurointerventional radiologists. Forty-one aneurysms were asymptomatic, and 16 patients had mass-induced neurological deficit. Clinical follow-up was available in 57 aneurysms with imaging follow-up at 6 months in 56. Permanent morbidity and mortality in the series was 0% at 6 months. Four TIAs and 1 small retinal branch occlusion occurred, but no stroke. The demonstrated aneurysm occlusion rate at 1 month was 61.9%, and the overall occlusion rate at 6 months was 85.7%. In cases previously untreated, the 6-month occlusion was 92.5%. Three of 6 aneurysms with a previous stent in situ were occluded. Two patients (3.5%) had asymptomatic in construct stenosis of >50%. Acute aneurysm-provoked mass effect resolved or improved significantly in all cases. CONCLUSIONS: Use of the PED is safe and efficacious in difficult aneurysms with a high occlusion rate at 6 months, but lower occlusion rates were seen in a small population with previous stents in situ. PMID- 21979493 TI - Optimized 3D magnetization-prepared rapid acquisition of gradient echo: identification of thalamus substructures at 3T. AB - BACKGROUND AND PURPOSE: Because the substructures of the thalamus are not visible on standard T1- and T2-weighted MR images, planning of deep brain stimulation implantation relies on stereotactic atlas coordinates. The goal of the present work was to test whether an optimized 3D MPRAGE protocol can depict thalamus substructures. MATERIALS AND METHODS: After optimization of the TI to maximize contrast between gray matter and white matter, 6 healthy subjects were scanned at 3T with the optimized 3D MPRAGE. The results were compared with stereotactic atlases, and 2 expert readers trained in thalamic anatomy identified the 4 large thalamic nuclei groups. RESULTS: There was a high agreement between the different atlases and the resulting MR images. The 4 large thalamic nuclei groups (anterior, lateral, medial, posterior) could be detected reliably. The inter reader consistency on the size and location was 75%-92%. CONCLUSIONS: The optimized 3D MPRAGE protocol improves contrast in the thalamus, and the 4 large thalamic nuclei groups can be identified with high inter-reader agreement. PMID- 21979494 TI - Brain perfusion in asphyxiated newborns treated with therapeutic hypothermia. AB - BACKGROUND AND PURPOSE: Induced hypothermia is thought to work partly by mitigating reperfusion injury in asphyxiated term neonates. The purpose of this study was to assess brain perfusion in the first week of life in these neonates. MATERIALS AND METHODS: In this prospective cohort study, MR imaging and ASL-PI were used to assess brain perfusion in these neonates. We measured regional CBF values on 1-2 MR images obtained during the first week of life and compared these with values obtained in control term neonates. The same or later MR imaging scans were obtained to define the extent of brain injury. RESULTS: Eighteen asphyxiated and 4 control term neonates were enrolled; 11 asphyxiated neonates were treated with hypothermia. Those developing brain injury despite being treated with induced hypothermia usually displayed hypoperfusion on DOL 1 and then hyperperfusion on DOL 2-3 in brain areas subsequently exhibiting injury. Asphyxiated neonates not treated with hypothermia who developed brain injury also displayed hyperperfusion on DOL 1-6 in brain areas displaying injury. CONCLUSIONS: Our data show that ASL-PI may be useful for identifying asphyxiated neonates at risk of developing brain injury, whether or not hypothermia is administered. Because hypothermia for 72 hours may not prevent brain injury when hyperperfusion is found early in the course of neonatal hypoxic-ischemic encephalopathy, such neonates may be candidates for adjustments in their hypothermia therapy or for adjunctive neuroprotective therapies. PMID- 21979495 TI - Differential action of 3-hydroxyanthranilic acid on viability and activation of stimulated lymphocytes. AB - Lymphocytes proliferation after antigen-driven activation leads to an increase in cell count, which could last some week, until apoptosis mechanisms allow the homeostatic control of the system. During the first days of this stimulation, activated lymphocytes display high resistance to apoptosis and to most immunosuppressive drugs. According to the literature, few compounds have been described to kill recently activated cells, by inhibiting metabolic processes fundamental to proliferation. The aim of our work was to evaluate comparatively these different compounds, in order to identify the best strategy to kill cells that have undergone proliferation, while sparing the repertoire of resting cells. After preliminary experiments, 3-HAA and bortezomib were selected as the most suitable compounds for our purposes. The possible synergic effect of 3-HAA with bortezomib or with manganese ions was also assessed. 3-HAA was confirmed to be the most reliable pharmacologic approach to inhibit proliferation with acceptable toxicity on resting cells. While in the case of PHA stimulation 3-HAA led to death of most lymphocytes, only a minor percentage of cells were killed after allo-stimulation, suggesting that the effect is proportional to the percentage of stimulated lymphocytes. Manganese ions further enhanced this effect, while results with bortezomib seemed to be less consistent. These results deserve further investigations to develop new procedures for targeting activated cells with pharmacological approaches. PMID- 21979500 TI - How well are color components of samples of the Natural Color System estimated? AB - The aim of this study was to determine how accurately color-normal subjects that have received basic information about, but do not have practical experience with, the Natural Color System (NCS) can estimate the Heringian components of a representative selection of samples. Twenty-five color-normal subjects, taking part in two trials with at least a 24 h gap between assessments, selected four samples representing individual unique hues (uHs) from a set of 40 highly chromatic NCS samples on a rotatable tray. The samples selected for assessment of components were displayed to the subjects who estimated the hue components of 16 high-chroma samples, hue and white/black components of 16 tonal color samples, and three achromatic samples with different blackness values. Variability in selection of samples representing uHs as well as the relationship between the subjects' estimates of unique hue components and the defined values of the system was obtained. It was found that hues alone are easier to correctly estimate than hues together with white and black and that the components of colors of higher chroma are easier to estimate accurately than those of lower chroma. It was also found that, for R and G, the mean uH choices of subjects differed very little from the NCS's R and G, whereas selections for yellow and blue deviated, the former by 1.22 hue steps (slightly greener than G90Y), and the latter by 1.36 hue steps (represented approximately by R85B). This may impact the accuracy of color models that employ NCS unique hues. PMID- 21979501 TI - On connectivity of wireless ultraviolet networks. AB - Non-line-of-sight optical communication can be enabled by modulating signals into an UV carrier and then transmitting them through an atmospheric scattering channel. This paper investigates some connectivity issues for such UV communication networks. We discuss k-connectivity in a multiuser interference environment. Compared with the studied case without considering multiuser interference in which more users bring higher probability of k-connectivity, a large number of noncoordinated users cause higher interference and limit the network performance. Thus, node density should be carefully designed in accordance with network configurations. Four typical scenarios are discussed, depending on whether each node transmitter is capable of adjusting its pointing angle and tracking a target receiver. They lead to different link losses and consequently the network k-connectivity properties. One of the cases simplifying the transceiver design for adjustable pointing is also illustrated, where each node is equipped with multiple transmitters to be activated via electronic on/off switching. The number of transmitters on a single node then becomes another critical parameter whose effect on k-connectivity is studied. These results will provide a guideline for system and network designers. PMID- 21979496 TI - Complement 3 is involved with ventilator-induced lung injury. AB - Humoral molecules can trigger injury on mechanically stressed and damaged tissue. We have studied the role of complement 3 (C3) in a mouse model of ventilator induced lung injury (VILI). Compared with sham-treated wild type (WT) mice, ventilated WT mice have reduced total bronchoalveolar lavage (BAL) cells; and elevated activities of thrombin and matrix metalloproteinases (MMPs), such as gelatinase/collagenase in the BAL fluid. In contrast, these parameters in ventilated C3 null mice are not significantly different from sham-treated WT and C3 null mice. In mechanically ventilated mice, thrombin activity and MMPs are lower in C3 null mice than in WT mice and are inversely correlated with total single BAL cells. C3 activation is associated with MMP activation in vitro. Pretreatment of WT mice with humanized cobra venom factor, which inactivates C3, reduces C3 deposition in the lung and increases total BAL cells in VILI. We propose that C3 is involved with VILI and inhibition of complement activation may be a potential therapeutic strategy. PMID- 21979502 TI - Effects of primary spherical aberration, coma, astigmatism and field curvature on the focusing of ultrashort pulses: homogenous illumination. AB - We analyze the spatiotemporal intensity of pulses with durations of 20 fs and shorter and a carrier wavelength of 810 nm at the paraxial focal plane of an achromatic doublet lens. The incident pulse is well-collimated, and we use the Seidel aberration theory for thin lenses to evaluate the phase change due to the aberrations of the lens. In a set of cemented thin lenses with the stop at the lens, there is only spherical aberration, coma, astigmatism and field curvature, whereas the distortion aberration in the phase front is zero. We analyze the effect of these aberrations in the focusing of ultrashort pulses for homogenous illumination. We will show that the temporal spreading introduced by these aberrations in pulses shorter than 20 fs at 810 nm is very small but the spatial spreading is not, which reduces the intensity of the pulse considerably. PMID- 21979504 TI - Second-order derivatives of a ray with respect to the variables of its source ray in optical systems containing spherical boundary surfaces. AB - The second-order derivative matrix of a scalar function with respect to a variable vector is called a Hessian matrix, which is a square matrix. Our research group previously presented a method for determination of the first-order derivatives (i.e., the Jacobian matrix) of a skew ray with respect to the variable vector of an optical system. This paper extends our previous methodology to determine the second-order derivatives (i.e., the Hessian matrix) of a skew ray with respect to the variable vector of its source ray when this ray is reflected/refracted by spherical boundary surfaces. The traditional finite difference methods using ray-tracing data to compute the Hessian matrix suffer from various cumulative rounding and truncation errors. The proposed method uses differential geometry, giving it an inherently greater accuracy. The proposed Hessian matrix methodology has potential use in optimization methods where the merit function is defined as ray aberrations. It also can be used to investigate the shape of the wavefront for a ray traveling through an optical system. PMID- 21979503 TI - Effects of primary spherical aberration, coma, astigmatism, and field curvature on the focusing of ultrashort pulses: Gaussian illumination and experiment. AB - We analyze the spatiotemporal intensity of Gaussian temporal envelope pulses with initial durations of 200 fs and a carrier wavelength of 810 nm at the paraxial focal plane of an achromatic doublet lens for a well-collimated incoming pulse beam by using the Seidel aberration theory for thin lenses with the stop at the lens. We analyze the effect of these aberrations in the focusing of ultrashort pulses for Gaussian illumination and present experimental results for 200 fs pulses focused by a near-IR achromatic doublet. PMID- 21979505 TI - Modal method based on subsectional Gegenbauer polynomial expansion for lamellar gratings. AB - A first approach of a modal method by Gegenbauer polynomial expansion (MMGE1) is presented for a plane wave diffraction by a lamellar grating. Modal methods are among the most popular methods that are used to solve the problem of lamellar gratings. They consist in describing the electromagnetic field in terms of eigenfunctions and eigenvalues of an operator. In the particular case of the Fourier modal method (FMM), the eigenfunctions are approximated by a finite Fourier sum, and this approximation can lead to a poor convergence of the FMM. The Wilbraham-Gibbs phenomenon may be one of the reasons for this poor convergence. Thus, it is interesting to investigate other basis functions that may represent the fields more accurately. The approach proposed in this paper consists in subdividing the pattern in homogeneous layers, according to the periodicity axis. The field is expanded, in each layer, on the basis of Gegenbauer's polynomials. Boundary conditions are rigorously written between adjacent layers; thus, an eigenvalue equation is obtained. The approach presented in this paper proves to describe the fields accurately. Finally, it is demonstrated that the results obtained with the MMGE1 are more accurate than several existing modal methods, such as the classical and the parametric FMM. PMID- 21979506 TI - Trajectories in parallel optics. AB - In our previous work we showed the ability to improve the optical system's matrix condition by optical design, thereby improving its robustness to noise. It was shown that by using singular value decomposition, a target point-spread function (PSF) matrix can be defined for an auxiliary optical system, which works parallel to the original system to achieve such an improvement. In this paper, after briefly introducing the all optics implementation of the auxiliary system, we show a method to decompose the target PSF matrix. This is done through a series of shifted responses of auxiliary optics (named trajectories), where a complicated hardware filter is replaced by postprocessing. This process manipulates the pixel confined PSF response of simple auxiliary optics, which in turn creates an auxiliary system with the required PSF matrix. This method is simulated on two space variant systems and reduces their system condition number from 18,598 to 197 and from 87,640 to 5.75, respectively. We perform a study of the latter result and show significant improvement in image restoration performance, in comparison to a system without auxiliary optics and to other previously suggested hybrid solutions. Image restoration results show that in a range of low signal-to-noise ratio values, the trajectories method gives a significant advantage over alternative approaches. A third space invariant study case is explored only briefly, and we present a significant improvement in the matrix condition number from 1.9160e+013 to 34,526. PMID- 21979507 TI - Precision and accuracy of the analog mean-delay method for high-speed fluorescence lifetime measurement. AB - The analog mean-delay (AMD) method is a new alternative method to measure the lifetime of a fluorescence molecule. Because of its powerful advantages of accurate lifetime determination, good photon economy, and a high photon detection rate, the AMD method is considered to be very suitable for high-speed confocal fluorescence lifetime imaging microscopy (FLIM). For the practical usage of the AMD method in FLIM (AMD-FLIM), detailed study on various experimental conditions and parameters that affect the precision and the accuracy of the AMD method is required. In this paper, we present the relation between the precision and accuracy of the lifetime versus iteration number in the AMD method, the best cutoff frequency of a low-pass filter used in the AMD-FLIM system for a given fluorophore, and the optimum position and width of the integration window by using Monte Carlo simulations and a series of AMD-FLIM experiments. PMID- 21979508 TI - From CIE 2006 physiological model to improved age-dependent and average colorimetric observers. AB - In the context of color perception on modern wide-gamut displays with narrowband spectral primaries, we performed a theoretical analysis on various aspects of physiological observers proposed by CIE TC 1-36 (CIEPO06). We allowed certain physiological factors to vary, which was not considered in the CIEPO06 framework. For example, we analyzed that the long-wave-sensitive (LWS) or medium-wave sensitive (MWS) peak wavelength shift in the photopigment absorption spectra, a factor not modeled in CIEPO06, contributed more toward observer variability than some of the factors considered in the model. Further, we compared the color matching functions derived from the CIEPO06 model and the CIE 10 degrees standard colorimetric observer to the average observer data from three distinct subgroups of Stiles-Burch observers, formed on the basis of observer ages (22-23 years, 27-29 years, and 49-50 years). The errors in predicting the x(lambda) and y(lambda) color-matching functions of the intragroup average observers in the long-wave range and in the medium-wave range, respectively, were generally more in the case of the CIEPO06 model compared to the 10 degrees standard colorimetric observer and manifested in both spectral and chromaticity space. In contrast, the short-wave-sensitive z10(lambda) function of the 10 degrees standard colorimetric observer performed poorly compared to the CIEPO06 model for all three subgroups. Finally, a constrained nonlinear optimization on the CIEPO06 model outputs showed that a peak wavelength shift of photopigment density alone could not improve the model prediction errors at higher wavelengths. As an alternative, two optimized weighting functions for each of the LWS and MWS cone photopigment densities led to significant improvement in the prediction of intra age-group average data for both the 22-23 year and 49-50 year age groups. We hypothesize that the assumption in the CIEPO06 model that the peak optical density of visual pigments does not vary with age is false and is the source of these prediction errors at higher wavelengths. Correcting these errors in the model can lead to an improved age-dependent observer and can also help update the current CIE 10 degrees standard colorimetric observer. Accordingly, it would reduce the discrepancies between color matches with broadband spectral primaries and color matches with narrowband spectral primaries. PMID- 21979509 TI - Distortion of terahertz signals due to imperfect synchronization with chirped probe pulses. AB - Terahertz (THz) signals measured by means of the spectral-encoding technique with different temporal discrepancies between probe pulses and THz signals are investigated. It is found that imperfect synchronization between the chirped probe and THz pulses induce a distortion and this distortion affects significantly the retrieved THz spectrum if the temporal discrepancy is large. The distortion becomes more prominent if the probe pulse length is less than the optimal chirped probe pulse duration. A simple approach is proposed to realize the synchronization and minimize the distortion. THz signals from a high-voltage biased air plasma filament are measured with this approach and distortion similar to the simulation results is observed. PMID- 21979510 TI - Multiresolution subspace-based optimization method for inverse scattering problems. AB - This paper investigates an approach to inverse scattering problems based on the integration of the subspace-based optimization method (SOM) within a multifocusing scheme in the framework of the contrast source formulation. The scattering equations are solved by a nested three-step procedure composed of (a) an outer multiresolution loop dealing with the identification of the regions of interest within the investigation domain through an iterative information acquisition process, (b) a spectrum analysis step devoted to the reconstruction of the deterministic components of the contrast sources, and (c) an inner optimization loop aimed at retrieving the ambiguous components of the contrast sources through a conjugate gradient minimization of a suitable objective function. A set of representative reconstruction results is discussed to provide numerical evidence of the effectiveness of the proposed algorithmic approach as well as to assess the features and potentialities of the multifocusing integration in comparison with the state-of-the-art SOM implementation. PMID- 21979511 TI - Pseudo-time particle filtering for diffuse optical tomography. AB - We recast the reconstruction problem of diffuse optical tomography (DOT) in a pseudo-dynamical framework and develop a method to recover the optical parameters using particle filters, i.e., stochastic filters based on Monte Carlo simulations. In particular, we have implemented two such filters, viz., the bootstrap (BS) filter and the Gaussian-sum (GS) filter and employed them to recover optical absorption coefficient distribution from both numerically simulated and experimentally generated photon fluence data. Using either indicator functions or compactly supported continuous kernels to represent the unknown property distribution within the inhomogeneous inclusions, we have drastically reduced the number of parameters to be recovered and thus brought the overall computation time to within reasonable limits. Even though the GS filter outperformed the BS filter in terms of accuracy of reconstruction, both gave fairly accurate recovery of the height, radius, and location of the inclusions. Since the present filtering algorithms do not use derivatives, we could demonstrate accurate contrast recovery even in the middle of the object where the usual deterministic algorithms perform poorly owing to the poor sensitivity of measurement of the parameters. Consistent with the fact that the DOT recovery, being ill posed, admits multiple solutions, both the filters gave solutions that were verified to be admissible by the closeness of the data computed through them to the data used in the filtering step (either numerically simulated or experimentally generated). PMID- 21979512 TI - Vectorized polarization-sensitive model of non-line-of-sight multiple-scatter propagation. AB - The existing Monte-Carlo-based non-line-of-sight (NLOS) multiple-scatter propagation model is extended to include polarization and also vectorized to improve the simulation speed by about 500 times. This model is validated by the noncoplanar single-scatter model; the results show a perfect match. Numerical examples for various polarization setups are obtained, and results show that the single-scatter and multiple-scatter signals are all polarization dependent. Therefore, NLOS polarized UV communication with a high data rate is achievable- the polarizing information is coded by a time-dependent polarizer, influenced by the atmospheric channel, and decoded according to the distribution characteristics of the scattered signals after the time-independent analyzers. PMID- 21979513 TI - Light scattering by optically soft large particles of arbitrary shape. AB - Light scattering by chaotically oriented optically soft large particles of arbitrary shape is considered within the framework of the Rayleigh-Gans approximation. It has been shown that outside the forward direction, the scattering pattern has the dependence of Deltak-4(1+cos2theta), where is an average particle surface area, Deltak is the difference between scattered and initial wave vectors, theta is the scattering angle, and this pattern is independent of particle shape. A simple approximating formula is suggested, which correctly describes the scattering pattern in the entire range of scattering angles. This formula is compared to the particular case of size-distributed spherical particles and is shown to have high accuracy. Also, it is shown that the inherent optical properties, as total, transport, and backward scattering coefficients, are determined by the specific particle surface area and the effective particle size. PMID- 21979514 TI - Compensation of shear waves in photoacoustic tomography with layered acoustic media. AB - An image reconstruction formula is presented for photoacoustic computed tomography that accounts for conversion between longitudinal and shear waves in a planar-layered acoustic medium. We assume the optical absorber that produces the photoacoustic wave field is embedded in a single fluid layer and any elastic solid layers present are separated by one or more fluid layers. The measurement aperture is assumed to be planar. Computer simulation studies are conducted to demonstrate and investigate the proposed reconstruction formula. PMID- 21979515 TI - Bessel-Gauss beams as rigorous solutions of the Helmholtz equation. AB - The study of the nonparaxial propagation of optical beams has received considerable attention. In particular, the so-called complex-source/sink model can be used to describe strongly focused beams near the beam waist, but this method has not yet been applied to the Bessel-Gauss (BG) beam. In this paper, the complex-source/sink solution for the nonparaxial BG beam is expressed as a superposition of nonparaxial elegant Laguerre-Gaussian beams. This provides a direct way to write the explicit expression for a tightly focused BG beam that is an exact solution of the Helmholtz equation. It reduces correctly to the paraxial BG beam, the nonparaxial Gaussian beam, and the Bessel beam in the appropriate limits. The analytical expression can be used to calculate the field of a BG beam near its waist, and it may be useful in investigating the features of BG beams under tight focusing conditions. PMID- 21979517 TI - Generating inhomogeneously polarized higher-order laser beams by use of diffractive optical elements. AB - We propose an improved version of the earlier developed optical arrangement for generating inhomogeneously polarized laser light modes with the aid of a diffractive optical element (DOE) with carrier frequency. By eliminating lenses from the optical arrangement, we achieve the miniaturization, reduced light losses, a smaller number of parameters being matched, and a simpler system adjustment procedure. Note that all the capabilities of the previous version, namely, the universality and simple readjustment to different polarization types, are fully retained. The numerical modeling of the polarization mode combiner has made it possible to analyze its performance and capabilities. In the experiments, the quality of the resulting beams is shown to be improved. For generating higher order cylindrical beams, a lower-order mode at the output of the polarization mode combiner is additionally transformed with a DOE that operates in the zero diffraction order, introducing radial phase changes. PMID- 21979516 TI - Quantitative determination of dynamical properties using coherent spatial frequency domain imaging. AB - Laser speckle imaging (LSI) is a fast, noninvasive method to obtain relative particle dynamics in highly light scattering media, such as biological tissue. To make quantitative measurements, we combine LSI with spatial frequency domain imaging, a technique where samples are illuminated with sinusoidal intensity patterns of light that control the characteristic path lengths of photons in the sample. We use both diffusion and radiative transport to predict the speckle contrast of coherent light remitted from turbid media. We validate our technique by measuring known Brownian diffusion coefficients (D(b)) of scattering liquid phantoms. Monte Carlo (MC) simulations of radiative transport were found to provide the most accurate contrast predictions. For polystyrene microspheres of radius 800 nm in water, the expected and fit D(b) using radiative transport were 6.10E-07 and 7.10E-07 mm2/s, respectively. For polystyrene microspheres of radius 1026 nm in water, the expected and fit D(b) were 4.7E-07 and 5.35 mm2/s, respectively. For scattering particles in water-glycerin solutions, the fit fractional changes in D(b) with changes in viscosity were all found to be within 3% of the expected value. PMID- 21979518 TI - Approximate Fourier phase information in the phase retrieval problem: what it gives and how to use it. AB - This work evaluates the importance of approximate Fourier phase information in the phase retrieval problem. The main discovery is that a rough phase estimate (up to pi/2 rad) allows development of very efficient algorithms whose reconstruction time is an order of magnitude faster than that of the current method of choice--the hybrid input-output (HIO) algorithm. Moreover, a heuristic explanation is provided of why continuous optimization methods like gradient descent or Newton-type algorithms fail when applied to the phase retrieval problem and how the approximate phase information can remedy this situation. Numerical simulations are presented to demonstrate the validity of our analysis and success of our reconstruction method even in cases where the HIO algorithm fails, namely, complex-valued signals without tight support information. PMID- 21979519 TI - Cumulative Reconstructor: fast wavefront reconstruction algorithm for Extremely Large Telescopes. AB - The Cumulative Reconstructor (CuRe) is a new direct reconstructor for an optical wavefront from Shack-Hartmann wavefront sensor measurements. In this paper, the algorithm is adapted to realistic telescope geometries and the transition from modified Hudgin to Fried geometry is discussed. After a discussion of the noise propagation, we analyze the complexity of the algorithm. Our numerical tests confirm that the algorithm is very fast and accurate and can therefore be used for adaptive optics systems of Extremely Large Telescopes. PMID- 21979520 TI - Comparison of polarimetric techniques for the identification of biological and chemical materials using Mueller matrices, lateral waves, and surface waves. AB - Optical polarimetric techniques to identify and characterize biological and chemical materials have received much attention recently for their broad applications in biophotonics, biochemistry, biomedicine, and pharmacology. We present here several options for the measurement of optical rotation, diattenuation, and the index of depolarization. These include polar decomposition, identification of specific pairs of Mueller matrix elements that are proportional to optical activity, and the cross-polarized components of lateral waves and surface waves at the interface between free space and the optically active material. PMID- 21979521 TI - Conditions under which two-element variable power lenses can be created. Part 1. Theoretical analysis. AB - The conditions under which a two-element variable power lens can be created are examined. Such a lens is defined as one in which the functional form of the optical effect created does not change as the elements translate with respect to one another--only the magnitude of the effect changes. It is found that only variable power optical effects that can be described by quadratic functions can be formed by laterally translating two-element variable power lenses. In the case of rotationally translating two-element variable power lenses, possible designs are found by mapping possible laterally translating designs from a Cartesian space to the polar coordinate space of the rotationally translating lens. PMID- 21979522 TI - Conditions under which two-element variable power lenses can be created. Part 2. Application to specific designs. AB - It was found in Part 1 of this paper [J. Opt. Soc. Am. A 28, 2148 (2011)] that only variable power optical effects that can be described by quadratic functions can be formed by laterally translating two-element variable power lenses. In the case of rotationally translating two-element variable power lenses, possible designs are found by mapping possible laterally translating designs from a Cartesian space to the polar coordinate space of the rotationally translating lens. Several designs that have been manufactured or suggested theoretically are examined in Part 2 to see which ones are true variable power lenses. PMID- 21979523 TI - Evolution properties of the intensity distribution of an anisotropic Gaussian Schell-model beam in a turbulent atmosphere. AB - An analytical expression for the cross-spectral density of an anisotropic Gaussian Schell-model (AGSM) beam propagating in a turbulent atmosphere is derived, which is featured by its clear physical meaning. The evolution properties of the intensity distribution of an AGSM beam in a turbulent atmosphere are studied thoroughly. It is found that owing to the anisotropy of the source coherence, the intensity distribution can have many different evolution processes; but under the influence of the turbulent atmosphere, it will finally take on a circular shape. The effects of lowering the source coherence on the circularization speed of the intensity distribution are also investigated. It is found that, when the anisotropy of the source coherence is taken into account, lowering the source coherence can accelerate or decelerate the circularization of the intensity distribution. We propose and demonstrate five kinds of conditions, and, under each condition, lowering the source coherence has a unique and definite effect on the circularization speed of the intensity distribution. In particular, we give an analysis about the equivalence between the problem studied in one of our five conditions and that in the work of Cai and He [Appl. Phys. Lett. 89, 041117 (2006)] and show that their relevant conclusion is incorrect. PMID- 21979524 TI - Subwavelength imaging by a graded-index photonic-crystal flat lens in a honeycomb lattice. AB - The left-handed behavior of a photonic-crystal flat lens with a graded index in a honeycomb lattice is proposed and theoretically studied. The performance of the flat superlens imaging of this structure has been demonstrated by finite difference time-domain simulations. The full width at half-maximum of the image decreases to 62% compared to that of the image of a photonic-crystal slab without a graded index. The evanescent waves can be amplified and propagate to the far field range. The image is not limited to be near the interface. The canalization effect of this structure is analyzed, and the tolerance of the edge cut of the graded-index structure is pretty good. PMID- 21979525 TI - A bound for the range of a narrow light beam in the near field. AB - We investigate the possibility of light beams that are both narrow and long range with respect to the wavelength. On the basis of spectral electromagnetic field representations, we have studied the decay of the evanescent waves, and we have obtained some bounds for the width and range of a light beam in the near-field region. The range determines the spatial bound of the near field in the direction of propagation. For a number of representative examples we found that narrow beams have a short range. Our analysis is based on the uncertainty relations between spatial position and spatial frequency. PMID- 21979526 TI - Effect of glare on reaction time for peripheral vision at mesopic adaptation. AB - When a bright light is present in the field of view, visibility is dramatically reduced. Many studies have investigated the effect of glare on visibility considering foveal vision. However, the effects on peripheral vision have received little attention. In a previous work [J. Opt. Soc. Am. A 25, 1790 (2008)], we showed that the effect of glare on reaction time (RT) for foveal vision at mesopic adaptation depends on the stimulus spatial frequency. In this work, we extend this study to peripheral vision. We measured the RT of achromatic sinusoidal gratings as a function of contrast for a range of spatial frequency, and eccentricity, and for two glare levels, in addition to the no-glare condition. Data were fitted with Pieron's law, following a linear relationship. We found that glare increases the slope of these lines for all conditions. These slopes seem to depend critically on eccentricity for 4 cycles/degree (c/deg), but not for 1 and 2 c/deg. We explain our results in terms of the contrast sensitivity (gain) of the underlying detection mechanisms. PMID- 21979527 TI - Hybrid finite element-boundary integral algorithm to solve the problem of scattering from a finite array of cavities with multilayer stratified dielectric coating. AB - This work presents a hybrid finite element-boundary integral algorithm to solve the problem of scattering from a finite array of two-dimensional cavities engraved in a perfectly electric conducting screen covered with multilayer stratified dielectric coating. The solution region is divided into interior regions containing the cavities and the region exterior to the cavities. The finite element formulation is applied only inside the interior regions to derive a linear system of equations associated with unknown field values. Using a two boundary formulation, the surface integral equation employing a closed-form multilayer Green's function in the spatial domain is applied at the opening of the cavities as a boundary constraint to truncate the solution region. The closed form Green's function in the spatial domain for multilayer planar coating is expressed in terms of complex images using the generalized pencil-of-function method in conjunction with a two-level sampling approach. Placing the truncation boundary at the opening of the cavities and inside the dielectric coating results in a highly efficient solution in terms of computational resources, which makes the algorithm well suited for optimization problems involving scattering from grating surfaces. The near fields are generated for array of cavities with different dimensions and inhomogeneous fillings covered with dielectric layers. PMID- 21979530 TI - Lauriston S. Taylor lecture: Radiation Protection and Public Policy in an Uncertain World. AB - Ionizing radiation is a known, well-documented, and reasonably well-quantified human cancer risk factor based on a remarkably consistent body of dose-response information from epidemiological studies of exposed populations supported by experimental studies using animal and cellular models. This fact is largely ascribable to the relative ease, compared to other carcinogens, of estimating radiation dose to organs and local tissues. Statistical models for radiation related cancer risk are increasingly relevant to both radiation protection policy and the adjudication of compensation claims for cancers diagnosed following occupational and environmental exposures to ionizing radiation, as discussed in a number of expert committee reports of national and international organizations concerned with radiation-related risks. These and other publications increasingly emphasize the relevance of well-quantified uncertainties in radiation-related risk projections, including upper and lower confidence or uncertainty bounds, for radiation protection. Finally, the wealth of detailed information provided by such quantitative uncertainty analysis approaches is highly relevant to radiation protection, which might be viewed as a political process that involves a diverse group of stakeholders who, individually, may be primarily concerned with avoiding possible radiation-related risks or with avoiding possibly unnecessary costs of risk reduction or unnecessary denial of benefits that require some radiation exposure, or with balancing both considerations to some degree. PMID- 21979531 TI - Welcome to the Forty-Sixth Annual NCRP Meeting. PMID- 21979532 TI - Risk communication, radiation, and radiological emergencies: strategies, tools, and techniques. AB - Risk communication is the two-way exchange of information about risks, including risks associated with radiation and radiological events. The risk communication literature contains a broad range of strategies for overcoming the psychological, sociological, and cultural factors that create public misperceptions and misunderstandings about risks. These strategies help radiation risk communicators overcome the challenges posed by three basic observations about people under stress: (1) people under stress typically want to know that you care before they care about what you know; (2) people under stress typically have difficulty hearing, understanding, and remembering information; (3) people under stress typically focus more on negative information than positive information. PMID- 21979533 TI - Crafting interactivity for stakeholder engagement: transforming assumptions about communication in science and policy. AB - The International Radiation Protection Association's guiding principles for stakeholder engagement focus on fostering, facilitating, and enabling interaction among stakeholders that is inclusive and fosters competent decision making. Implicit in these standards is a call to cultivate knowledge and competence in designing communication for stakeholder engagement among radiation protection professionals. Communication as design is an approach to risk communication in science and policy that differs from, yet complements, the more well-known communication practices of informing and persuading. Design focuses on the recurring practical problem faced by professionals in making communication possible among stakeholders where it has otherwise been difficult, impossible, or even unimagined. The knowledge and competence associated with design involves principles for crafting interactivity across a variety of mediated and non mediated encounters among stakeholders. Risk communication can be improved by cultivating expertise in scalable communication design that embraces the demands of involvement without abandoning the need for competence in science and policy communication. PMID- 21979534 TI - One perspective on stakeholder involvement at Hanford. AB - The Hanford nuclear site in Washington State had a major role in the production of nuclear weapons materials during the Manhattan Project in World War II and during the Cold War that followed. The production of weapons-grade radionuclides produced a large amount of radioactive byproducts that have been stored since the mid-1900s at the Hanford Site. These by-product radionuclides have leaked from containment facilities into the groundwater, contaminated buildings used for radionuclide processing, and also contaminated the nuclear reactors used to produce weapons-grade uranium and plutonium. This issue has been a major concern to Hanford stakeholders for several decades, and the U.S. Department of Energy, the U.S. Environmental Protection Agency, and the Washington State Department of Ecology established a Tri-Party Agreement in 1989, at which time Hanford ceased production of nuclear weapons materials and began a major effort to clean up and remediate the Hanford Site's contaminated groundwater, soil, and facilities. This paper describes the concerns of stakeholders in the production of nuclear weapons, the secrecy of Hanford operations, and the potential impacts to public health and the environment from the unintended releases of weapons-grade materials and by-products associated with their production at the Hanford Site. It also describes the involvement of public stakeholders in the development and oversight by the Hanford Advisory Board of the steps that have been taken in cleanup activities at the Hanford Site that began as a major effort about two decades ago. The importance of involvement of the general public and public interest organizations in developing and implementing the Hanford cleanup strategy are described in detail. PMID- 21979535 TI - Basic concepts and examples of effective risk communication panel summary: getting the message out. PMID- 21979536 TI - Panel on "communication, terrorism and homeland security: new research, recent experience, emerging challenges". PMID- 21979537 TI - Communications, terrorism, and homeland security: new approaches, projects, and initiatives. PMID- 21979538 TI - The London polonium incident: lessons in risk communications. AB - Public responses to large-scale radiological incidents are often thought to be disproportionate to the objective risk and can involve widespread societal disruption. Recent experiences of the (200)Po incident in central London suggest that public responses depend heavily on the nature of the incident and the effectiveness of risk communication efforts. This paper describes the outcome of several studies done in the aftermath of the (200)Po incident that suggest the reaction of the public on this occasion was muted, even for those directly affected. However, the desire for accurate, up-to-date and individually-tailored information was strong, and satisfaction with the efforts of the responding agencies was mediated by this information provision. A small minority of individuals was difficult to reassure effectively. This group may confer a particular drain on resources. Lessons for the risk communication efforts of public health responders are identified, in particular the importance of helping individuals to identify their risk of exposure, understand the difference between acute and chronic effects of exposure, and appreciate the meaning of any test results. Attempts at providing reassurance in the absence of specific information are likely to be counterproductive in any future radiological incident. PMID- 21979539 TI - Risk communication and radiological/nuclear terrorism: a strategic view. AB - It is now widely recognized that effective communication is a crucial element in radiological/nuclear terrorism preparedness. Whereas in the past, communication and information issues were sometimes viewed as secondary in comparison with technical concerns, today the need to improve risk communication, public information, and emergency messaging is seen as a high priority. The process of improving radiological/nuclear terrorism risk communication can be conceptualized as occurring in four overlapping phases. The first phase involves the recognition that communication and information issues will be pivotal in shaping how a radiological/nuclear terrorism incident unfolds and in determining its outcome. This recognition has helped shape the second phase, in which various research initiatives have been undertaken to provide an empirical basis for improved communication. In the third and most recent phase, government agencies, professional organizations and others have worked to translate research findings into better messages and informational materials. Like the first and second phases, the third phase is still unfolding. The fourth phase in risk communication for radiological/nuclear terrorism-a mature phase-is only now just beginning. Central to this phase is a developing understanding that for radiological/nuclear terrorism risk communication to be fully effective, it must go beyond crafting better messages and materials (as essential as that may be). This emerging fourth phase seeks to anchor radiological/nuclear communication in a broader approach: one that actively engages and partners with the public. In this article, each of the four stages is discussed, and future directions for improving radiological/nuclear terrorism risk communication are explored. PMID- 21979540 TI - Federal interagency communication strategies for addressing radiation emergencies and other public health crises. AB - Federal agencies have a variety of roles and responsibilities related to communicating with the public before, during, and after a radiological emergency. To better understand the various efforts currently underway, the Radiation Studies Branch of the Centers for Disease Control and Prevention convened a roundtable of representatives from federal agencies with responsibility for communicating with the public about radiation emergencies. Roundtable participants shared valuable information about efforts underway to develop information and messages for a variety of audiences and agreed that continued interagency coordination and dialogue about communication before, during, and after an event are needed. The group suggested several strategies for future collaborative efforts and indicated a desire to continue working together to develop and assess messages for radiological emergency preparedness and response. The group also recommended that more work be done to determine whether messages need to be packaged or tailored for specific special populations and suggested that more research be conducted to answer questions about specific audience/cultural needs around communicating radiation risks. Since this roundtable, attendees have continued to work together to develop and test messages for the public. PMID- 21979541 TI - Communication of benefits and risks of medical radiation: a historical perspective. AB - X-rays were discovered by Wilhelm Rontgen in 1895. Within one year, benefits of x rays, such as visualization of fractures, and detriments, such as x-ray dermatitis, were recognized. Nobel Laureates Pierre and Marie Sklodowska Curie discovered the radioactive element radium in 1898, and a year later the application of radiation to cure cancer was reported. A significant price was paid for this: Marie Curie died of aplastic anemia related to her radiation exposure, and her daughter Irene Joliot Curie, Nobelist for radiochemical research, died of radiation-induced leukemia. Internationally developed radiation protection recommendations were formalized starting in the late 1920s. The increasing use of ionizing radiation in medical diagnosis and radiation therapy has brought significant societal benefits. Known risks of therapeutic radiation include coronary artery disease and secondary malignancy. However, recently concerns have been raised of possible very small but incremental increases in malignancies due to diagnostic medical radiation. Patients are largely unaware of, and referring physicians and even radiologists often underestimate, the carcinogenic effects of radiation. There is a need to determine the appropriateness of imaging tests that use ionizing radiation prior to performance; optimize imaging protocols to reduce unnecessary radiation; include patients in the decision process and encourage and enable them to track their radiation exposure; and promote education about medical radiation to patients, referring physicians, radiologists, and members of the public. The basic radiation protection principles of justification, optimization, and application of dose limits still pertain. PMID- 21979542 TI - Toward a holistic approach in the presentation of benefits and risks of medical radiation. AB - Frequently messages are conveyed about benefit and risk in medical imaging or in imaging-guided medical intervention that are quite different from the intended communication. This is because communication is not merely the words used to express an idea. The message involves many personal factors on the part of the communicator and on the part of the audience. The intent of this article is to disclose some of the underlying factors that disproportionately bias communication of benefit and risk. Suggestions on how to develop a holistic communication of benefits and risks are presented. It is recommended that communication about the application of radiation to patients be disassociated from standard radiation protection concepts. The medical profession should develop unique communication tools to deliver a message that focuses on benefit/risk as a holistic entity, not benefit or risk as separate entities. PMID- 21979543 TI - Communicating the benefits/risks of radiation therapy: maintaining context, perspective, and reassurance. AB - When communicating the benefits and risks of radiation therapy, it is important to provide context, perspective, and reassurance. Radiation is inherently frightening. While this may make discussions about medical radiation's benefits risks challenging, it also reinforces our responsibility for meaningful and clear discussions with patients, families, colleagues in non-radiation fields, and the public. We need to clearly acknowledge the risks of radiation but also reinforce therapeutic benefits of radiation. For most clinical situations, the benefit-risk ratio is favorable for radiation. Further, we must provide reassurance that we are doing what we can to minimize the risks. This approach helps to build confidence in the radiation team. Obtaining informed consent for patients recently diagnosed with cancer is challenging, since receiving the diagnosis is often extraordinarily stressful. Many patients do not remember or understand verbal discussions at the time of initial consultation. Thus, it is often helpful to provide written information that can be digested by the patient over time. Formal benefit-risk discussions often continue throughout the course of radiation. Further, patients' interactions with all members of the radiation team (e.g., asking questions, understanding the processes) help to augment these formal discussions and build confidence in the entire team-a critical component of informed consent. Since many of the risks of radiation occur months to years post-treatment, discussions with patients need also to consider their prognosis and longevity. PMID- 21979544 TI - Just the facts: mammography saves lives with little if any radiation risk to the mature breast. AB - Mammography screening is one of the major medical advances of the past several decades. Prior to 1990, the death rate from breast cancer had been unchanged in 50 y. Mammography screening began on a national scale in the middle of the 1980s and, as would be expected, the death rate from breast cancer began to drop in 1990. Since 1990, the death rate from breast cancer has decreased by 30%. Studies in the Netherlands and Sweden, using direct measurements in the general population, show that most of the decrease is due to mammography screening beginning at the age of 40 y, with a small component due to improved therapies (therapy is more effective when cancers are small and earlier stage). A major concern raised in the 1970s was that the radiation from mammography might cause more cancers than would be cured. Not only did this prove to be a huge overestimate, but it has become clear that it is radiation delivered to very young women (teenagers and women in their early twenties), before terminal differentiation has taken place, that presents the greatest risk. Once the breast has differentiated, the risk from radiation is markedly reduced. By the time women reach their late thirties and early forties, there is no measurable risk from mammographic doses, and even the extrapolated risk is far below even the smallest benefit from screening. Hundreds of millions of mammograms have been obtained since the 1980s. If mammography were causing cancers, the incidence of breast cancer would be increasing. In fact, it is decreasing. Women need to be provided with this information to be reassured that mammograms save lives and that the radiation risk is minimal. PMID- 21979545 TI - Communicating the harmful effects of radiation exposure from medical imaging: malpractice considerations. AB - Concerns about possible harmful effects of exposure to radiation arising from diagnostic radiologic procedures have existed in both the scientific and lay communities for many decades. There is, however, no question that the degree of concern over the past years has escalated to the "anxiety" if not the "fear" level. Potential exposure to radiation is not a new issue, but it is certainly a "hot" issue. Americans were exposed to more than six times as much ionizing radiation from diagnostic medical procedures in 2006 than they were in early 1980s. To what extent this increased exposure elevates the risk of genetic mutations and/or development of cancer is not known with any degree of certainty. The available data are subject to varying interpretations, often debatable and thus controversial. What should be communicated to the public? The medical and scientific communities must encourage public attention and discussion regarding radiologic imaging and associated radiation exposure. They must talk to the public sensibly about the uncertainty regarding the hazards of radiation exposure. Exposure to imaging involving radiation and the hazards related to such exposure has myriad medical/legal ramifications. There has never been a successful medical malpractice lawsuit that alleged development of cancer or genetic defects resulting from diagnostic x-ray examinations. However, there have been and continue to be lawsuits filed alleging soft tissue injury resulting from overexposure to diagnostic radiologic equipment and cancer caused by overexposure to radiation oncology equipment. It is quite likely that lawsuits alleging development of cancer arising from diagnostic imaging using standard levels of ionizing radiation will be forthcoming. How the courts will deal with these remains to be determined. PMID- 21979546 TI - Communication of radiation benefits and risks in decision making: communication on children's imaging and computed tomography. PMID- 21979547 TI - Beyond dose assessment: using risk with full disclosure of uncertainty in public and scientific communication. AB - Evaluations of radiation exposures of workers and the public traditionally focus on assessments of radiation dose, especially annual dose, without explicitly evaluating the health risk associated with those exposures, principally the risk of radiation-induced cancer. When dose is the endpoint of an assessment, opportunities to communicate the significance of exposures are limited to comparisons with dose criteria in regulations, doses due to natural background or medical x-rays, and doses above which a statistically significant increase of disease has been observed in epidemiologic studies. Risk assessment generally addresses the chance (probability) that specific diseases might be induced by past, present, or future exposure. The risk of cancer per unit dose will vary depending on gender, age, exposure type (acute or chronic), and radiation type. It is not uncommon to find that two individuals with the same effective dose will have substantially different risks. Risk assessment has shown, for example, that: (a) medical exposures to computed tomography scans have become a leading source of future risk to the general population, and that the risk would be increased above recently published estimates if the incidence of skin cancer and the increased risk from exposure to x-rays compared with high-energy photons were taken into account; (b) indoor radon is a significant contributor to the baseline risk of lung cancer, particularly among people who have never smoked; and (c) members of the public who were exposed in childhood to I in fallout from atmospheric nuclear weapons tests and were diagnosed with thyroid cancer later in life would frequently meet criteria established for federal compensation of cancers experienced by energy workers and military participants at atmospheric weapons tests. Risk estimation also enables comparisons of impacts of exposures to radiation and chemical carcinogens and other hazards to life and health. Communication of risk with uncertainty is essential for reaching informed consent, whether communicating to a larger community debating the tradeoffs of risks and benefits of an action that involves radiation exposure or communicating at the level of a physician and patient. PMID- 21979548 TI - Using the IRPA Guiding Principles on Stakeholder Engagement: putting theory into practice. AB - The International Radiation Protection Association (IRPA) published their Guiding Principles for Radiation Protection Professionals on Stakeholder Engagement in February 2009. The publication of this document is the culmination of four years of work by the Spanish Society for Radiological Protection, the French Society of Radioprotection, the United Kingdom Society of Radiological Protection, and the IRPA organization, with full participation by the Italian Associate Society and the Nuclear Energy Agency's Committee on Radiation Protection and Public Health. The Guiding Principles provide field-tested and sound counsel to the radiation protection profession to aid it in successfully engaging with stakeholders in decision-making processes that result in mutually agreeable and sustainable decisions. Stakeholders in the radiation protection decision making process are now being recognized as a spectrum of individuals and organizations specific to the situation. It is also important to note that stakeholder engagement is not needed or advised in all decision making situations, although it has been shown to be a tool of first choice in dealing with such topics as intervention and chronic exposure situations, as well as situations that have reached an impasse using traditional approaches to decision-making. To enhance the contribution of the radiation protection profession, it is important for radiation protection professionals and their national professional societies to embrace and implement the IRPA Guiding Principles in a sustainable way by making them a cornerstone of their operations and an integral part of day-to-day activities. PMID- 21979549 TI - Community Environmental Monitoring Program: a case study of public education and involvement in radiological monitoring. AB - The public's trust in the source of information about radiation is a key element of its acceptance. The public tends to trust two groups where risk communication is concerned: (1) scientists with expertise who are viewed as acting independently; and (2) friends, family, and other close associates who are viewed as sharing the same interests and concern, even if they have less knowledge of the subject. The Community Environmental Monitoring Program (CEMP) bridges both of these groups by having members of the public help operate and communicate results of a network of 29 radiation monitoring stations around the Nevada National Security Site (NNSS), formerly known as the Nevada Test Site (NTS), the principal continental location where the United States conducted nuclear tests. The CEMP stations, spread across a 160,000 km area, help provide evidence to the public that no releases of radiation of health concern are occurring from the NNSS to public receptors. The stations provide continuous measurements of gamma radiation and collect air particulate samples that are analyzed for radioactivity and meteorological measurements that aid in interpreting variations in background radiation. A public website (http://cemp.dri.edu) provides data for most instruments. Twenty-three of the 29 stations upload their data in near-real time to a public website as well as to digital readout displays at the stations, both of which are key elements in the CEMP's transparency. The remaining six stations upload their data hourly. Public stakeholders who are direct participants provide the most significant element of the CEMP. The "Community Environmental Monitors," who are residents of towns where the stations are located, are part of the chain of-custody for the air samples, perform minor station maintenance, and most significantly in terms of trust, serve as lay experts on issues concerning the NNSS and on ionizing radiation and nuclear technologies in general. The CEMP meets nearly all of the principles for stakeholder engagement identified by the International Radiation Protection Association. PMID- 21979550 TI - Psychosocial and health impacts of uranium mining and milling on Navajo lands. AB - The uranium industry in the American Southwest has had profoundly negative impacts on American Indian communities. Navajo workers experienced significant health problems, including lung cancer and nonmalignant respiratory diseases, and psychosocial problems, such as depression and anxiety. There were four uranium processing mills and approximately 1,200 uranium mines on the Navajo Nation's over 27,000 square miles. In this paper, a chronology is presented of how uranium mining and milling impacted the lives of Navajo workers and their families. Local community leaders organized meetings across the reservation to inform workers and their families about the relationship between worker exposures and possible health problems. A reservation-wide effort resulted in activists working with political leaders and attorneys to write radiation compensation legislation, which was passed in 1990 as the Radiation Exposure Compensation Act (RECA) and included underground uranium miners, atomic downwinders, and nuclear test-site workers. Later efforts resulted in the inclusion of surface miners, ore truck haulers, and millworkers in the RECA Amendments of 2000. On the Navajo Nation, the Office of Navajo Uranium Workers was created to assist workers and their families to apply for RECA funds. Present issues concerning the Navajo and other uranium-impacted groups include those who worked in mining and milling after 1971 and are excluded from RECA. Perceptions about uranium health impacts have contributed recently to the Navajo people rejecting a resumption of uranium mining and milling on Navajo lands. PMID- 21979551 TI - Communication of radiation benefits and risks in decision making: some lessons learned. AB - This paper is focused on summarizing the "lessons learned" from discussions at the 2010 NCRP Annual Meeting on effective communications on the subject of radiation benefits and risks in public exposures. Five main lessons learned are discussed in regard to effective methods of public communication: the use of new social media communication tools such as Facebook and Twitter, emergency situations that require rapid societal and personal messaging, medical radiological procedures where benefits must be described in comparison to long term health risks of radiation exposures, and information that should be provided to stakeholders in situations such as environmental radionuclide contamination to which members of the public may be exposed. It is concluded that effective communications in which radiation benefits are contrasted with health risks of exposure are an important aspect of making and implementing decisions on employing radiation health protection procedures. PMID- 21979555 TI - Identifying individuals with an anterior cruciate ligament-deficient knee as copers and noncopers: a narrative literature review. AB - STUDY DESIGN: Narrative literature review. OBJECTIVES: First, to explore the differences and outcomes between individuals who have had anterior cruciate ligament (ACL) reconstruction and those who did not undergo surgical intervention, following a tear of the ACL. Second, to review the evidence related to the ability to identify individuals who may or may not need surgery after an ACL rupture. Finally, to describe the differences between copers and noncopers. BACKGROUND: ACL rupture may result in increased tibiofemoral laxity and impaired neuromuscular function, which ultimately may lead to knee instability and dysfunction. Individuals who opt to choose surgery due to these changes may be defined as "noncopers." Conversely, those individuals who have an ACL-deficient knee without functional impairment and instability and successfully resume preinjury activity levels without surgical intervention may be defined as "copers." METHODS: An electronic search was conducted up to April 2011, using medical subject headings and free-text words. The subject-specific search was based on the terms "anterior cruciate ligament reconstruction versus conservative treatment," "copers," "noncopers." RESULTS: A similar percentage of copers and noncopers return to sporting activity. Three papers used an algorithm and screening examination involving individuals with ACL injuries. Evidence suggests that, as opposed to copers, noncopers have deficits in quadriceps strength, vastus lateralis atrophy, quadriceps activation deficits, altered knee movement patterns, reduced knee flexion moment, and greater quadriceps/hamstring cocontraction. CONCLUSION: ACL screening examination showed preliminary evidence for detecting potential copers. Objective differences exist between copers and noncopers. Individuals with ACL injury should be informed of the possibility of good knee function following a nonoperative rehabilitation program. PMID- 21979556 TI - Intraoperative neurophysiological monitoring during surgery for Chiari malformations. AB - Reports on the use of intraoperative neurophysiological monitoring (INM) techniques during surgery for Chiari malformations are anecdotal. There are almost no data on significant intraoperative worsening in either somatosensory evoked potentials (SEPs) or brainstem auditory-evoked potentials (BAEPs) during surgery that would have alerted the surgeon to modify the surgical strategy. Yet, a few reports suggest that INM may play a role in preventing spinal cord injury during positioning of the patient. Overall, the use of INM in this type of surgery can be considered only as an option. More speculatively, INM adds information to the ongoing discussion on the most appropriate surgical technique for posterior fossa decompression in Chiari malformations. This debate applies especially to children where a more conservative approach is advisable to reduce the complications. Studies on the conduction time of BAEPs provide some evidence that, from a merely neurophysiological perspective, most of the improvement occurs after bony decompression and removal of the dural band at the level of the atlanto-occipital membrane, not after duraplasty. PMID- 21979557 TI - Trigeminal neuralgia as unusual isolated symptom of fungal paranasal sinusitis in patients with haematological malignancies. AB - A sinonasal infection is a frequent complication in patients with haematological malignancies, and may represent a challenge in terms of differential diagnosis between a bacterial or fungal infective process and tumour localization. A timely and correct diagnosis in these patients is critical and, therefore, may require consultation of specialists outside of haematology; an incorrect diagnosis which underestimates the seriousness of the infection can be fatal. Symptomatic trigeminal neuralgia resulting from direct compression or perineural invasion from malignancy is not uncommon in the literature. However, trigeminal neuralgia as an isolated symptom at the onset of a bacterial or invasive fungal sinusitis is rare and risks going unnoticed. The authors herein describe three cases of patients affected by acute myeloid leukaemia or lymphoma in which an invasive fungal sinusitis appeared at the onset as an isolated trigeminal neuralgia, with pain located along the distribution area of the second branch of the trigeminal nerve. Only after referring these patients to a neurologist for a host of neurological exams it was possible to confirm a diagnosis of secondary maxillary sinus fungal involvement. PMID- 21979558 TI - Functional outcome in patients with pontine infarction after acute rehabilitation. AB - We examined the clinical features of patients with pontine infarction in the acute stage and the factors affecting functional prognosis and outcome. Lesions, neurological manifestations at initial physical status examinations, cognitive function, swallowing function and outcome [activities of daily living (ADL), status of nutritional intake at discharge and destination after discharge] were evaluated in 68 patients (47 males and 21 females) who had pontine lesions with acute phase cerebral infarction. The mean length of stay was 24.4 days. The symptoms (number of patients) observed included paralysis (50), dysarthria (47), ataxia (18), diplopia (11), dysphagia (49) and poor cognitive performance (37). The types of lesions (number of patients) included lacunar infarcts in the ventral pontine area (15), lacunar infarcts in the dorsal pontine area (13) and large lacunar infarcts (LLIs) (41). After hospital discharge, 23 patients were discharged home, 44 were transferred to another hospital and 1 died. Twenty-three patients were on a regular diet, 22 were receiving a dysphagia diet and 22 were on enteral feeding at discharge. Patients with LLIs more frequently had poor cognitive performance, paralysis, dysphagia at discharge and a tendency for a longer length of stay compared with patients who had lacunar infarct. Most patients who returned home were those who were younger in age, had fewer neurological symptoms, had better cognitive function and ADL performance, and could ingest food. In an acute hospital, age, neurological symptoms, ADL, cognitive function, and dysphagia were considered important factors for determining the outcome in patients with pontine infarction. PMID- 21979559 TI - Optimized Ar(+)-ion milling procedure for TEM cross-section sample preparation. AB - High-quality samples are indispensable for every reliable transmission electron microscopy (TEM) investigation. In order to predict optimized parameters for the final Ar(+)-ion milling preparation step, topographical changes of symmetrical cross-section samples by the sputtering process were modeled by two-dimensional Monte-Carlo simulations. Due to its well-known sputtering yield of Ar(+)-ions and its easiness in mechanical preparation Si was used as model system. The simulations are based on a modified parameterized description of the sputtering yield of Ar(+)-ions on Si summarized from literature. The formation of a wedge shaped profile, as commonly observed during double-sector ion milling of cross section samples, was reproduced by the simulations, independent of the sputtering angle. Moreover, the preparation of wide, plane parallel sample areas by alternating single-sector ion milling is predicted by the simulations. These findings were validated by a systematic ion-milling study (single-sector vs. double-sector milling at various sputtering angles) using Si cross-section samples as well as two other material-science examples. The presented systematic single-sector ion-milling procedure is applicable for most Ar(+)-ion mills, which allow simultaneous milling from both sides of a TEM sample (top and bottom) in an azimuthally restricted sector perpendicular to the central epoxy line of that cross-sectional TEM sample. The procedure is based on the alternating milling of the two halves of the TEM sample instead of double-sector milling of the whole sample. Furthermore, various other practical aspects are issued like the dependency of the topographical quality of the final sample on parameters like epoxy thickness and incident angle. PMID- 21979560 TI - Introductory address for John Howland Award recipient, Russell Chesney, M.D. PMID- 21979561 TI - American Pediatric Society's 2011 John Howland Award Acceptance Lecture: lessons from models of disease. PMID- 21979562 TI - A novel mutation and unusual clinical features in a patient with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. AB - We report a patient with immune dysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome with a novel splicing mutation of the FOXP3 gene. The patient is a boy, born at 39 + 2 weeks gestation with a birth weight of 3,280 g. The family history was unremarkable. He was well until 11 months of age, when he was diagnosed with type 1 diabetes mellitus. The level of urine C-peptide was 0.58 MUg/day (normal range, 44-116 MUg/day). Glutamic acid decarboxylase autoantibody was not detected, but a high level of anti-insulin antibody (50 IU/mL; normal range, <5 IU/mL) was noted. This patient presented with unusual clinical features, including pure red cell aplasia, membranous glomerulopathy, and posterior reversible encephalopathy syndrome after a vaccination against influenza A H1N1 virus. The diagnosis of IPEX was made when the patient was 11 years old, which is quite late compared with typical cases. CONCLUSION: Although IPEX syndrome is usually a disease of infancy, it should not be ruled out solely on the basis of age. IPEX presentation is so variable that it should be suspected in a male child with one or more autoimmune disorders and severe infections. PMID- 21979563 TI - Waist circumference percentiles for Portuguese children and adolescents aged 10 to 18 years. AB - The purposes of this study were to develop age- and sex-specific waist circumference reference data for Portuguese children and adolescents aged 10-18 years and to compare them with those from other countries. This was a school based study performed in Portugal. A total of 22,003 children and adolescents aged 10-18 years were included in the study. Smoothed sex- and age-specific 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentile curves of waist circumference were estimated using Cole's lambda-mu-sigma method. Waist circumference values increased with age in both boys and girls, and boys had higher values than girls at every age and percentile. In both sexes, the Portuguese values in the 90th percentile were closer to the Bolivian values and considerably lower than those of the American children for all age groups. CONCLUSION: The data presented provide information for abdominal risk assessment and clinical and lifestyle intervention; our results also provide useful baseline data information for the implementation of a surveillance system required to monitor trends and factors associated with abdominal obesity in children and adolescents. PMID- 21979564 TI - Assessing the association between low back pain, quality of life, and life events as reported by schoolchildren in a population-based study. AB - Low back pain (LBP) is prevalent in teenagers but not necessarily detrimental to their quality of life (QoL). This population-based study evaluated a global QoL score and the association between LBP and life events and/or health problems affecting QoL. Schoolchildren were investigated in Fribourg-Switzerland and Barcelona-Spain. In addition to the KIDSCREEN, a health-related QoL questionnaire, two Numerical Rating Scales were used to assess QoL in general, and the influence of LBP on QoL. Open questions explored life events and health problems affecting QoL; responses were submitted to content analysis. Adolescents were stratified: Pain-free, Other pain (OP), isolated LBP (IsoLBP), LBP + other pains (LBP + OP), and LBP + whole-body pain (LBP + WBP). Between-group comparisons were performed using Chi-squared tests and ANOVA. Linear regression analysis was performed to assess between-group differences in the impact of LBP on QoL. Schoolchildren (1,470) (mean age = 15.05 years, 52.6% = boys) completed the questionnaire. LBP lasting >1 day in the last month was reported by 39.8% (N = 560): of them, 242 (43.2%) reported IsoLBP, 268 (47.9%) LBP + OP, and 50 (9.1%) LBP + WBP. QoL was lower in LBP + WBP (mean = 6.44 vs. LBP + OP = 7.8; IsoLBP = 7.6, OP = 7.96, Pain-free = 8.1; p < 0.001). There were 18.5% who reported health problems and 15.3% life events with a perceived impact on QoL. Prevalence was higher in LBP + WBP with >30% of this group identifying life events and/or health problems vs. 10-12% in PFree or IsoLBP groups (p < 0.001). IsoLBP affected QoL marginally (mean = 2.4 +/- 2.2) compared to LBP + WBP (mean = 4.9 +/- 2.4) (p < 0.001). LBP affected QoL marginally. These results stress the distinction between disease and common life experience. They also indicate the potential value of global QoL assessments in clinical settings. PMID- 21979565 TI - The simultaneous presence of health risk behaviors in freshman college students in Brazil. AB - The objective of this study was to assess the prevalence and factors associated with simultaneous health risk behaviors in freshmen college students enrolled in a Brazilian university. We interviewed 738 students (59.2% men) with average age of 20.1 years (CI 95%: 19.8-20.5). The risk behaviors assessed were smoking habit, alcohol use, unhealthy diet and physical inactivity. Independent variables were sex, age, employment, marital status, maternal education, study shift and socioeconomic level. It was found that 8.7% were smokers, 45.9% showed alcohol abuse, 59.4% had inadequate diet and 18.5% were physically inactive. Of the students, 20.2% showed no risk behavior, 39.1% one behavior, 29.0% two risk behaviors and 11.7% three and/or four risk behaviors. Males (OR: 2.04, CI 95%: 1.13-3.67) and night shift students (OR: 1.83, CI 95%: 1.01-3.33) were more likely to have three and/or four risk behaviors. Health promotion interventions focusing simultaneous behavior changes should be employed at the university. PMID- 21979566 TI - Fabrication of sticky and slippery superhydrophobic surfaces via spin-coating silica nanoparticles onto flat/patterned substrates. AB - Silica nanoparticles were spin-coated onto a flat/patterned (regular pillar-like) substrate to enhance the surface roughness. The surface was further modified by a self-assembled fluorosilanated monolayer. The advancing/receding contact angle and sliding angle measurements were performed to determine the wetting behavior of a water droplet on the surface. It is interesting to find that a transition from a Wenzel surface to a sticky superhydrophobic surface is observed due to the spin-coating silica nanoparticles. A slippery superhydrophobic surface can be further obtained after secondary spin-coating with silica nanoparticles to generate a multi-scale roughness structure. The prepared superhydrophobic substrates should be robust for practical applications. The adhesion between the substrate and nanoparticles is also examined and discussed. PMID- 21979567 TI - Microelectrode arrays fabricated using a novel hybrid microfabrication method. AB - We present novel hybrid microfabrication methods for microelectrode arrays that combine microwire assembly, microelectromechanical systems (MEMS) manufacturing techniques and precision tool-based micromachining. This combination enables hybrid microfabrication to produce complex geometries and structures, increase material selection, and improve integration. A 32-channel shank microelectrode array was fabricated to highlight the hybrid microfabrication techniques. The electrode shank was 130 MUm at its narrowest, had a 127 MUm thickness and had iridium oxide electrode sites that were 25 MUm in diameter with 150 MUm spacing. Techniques used to fabricate this electrode include microassembly of insulated gold wires into a micromold, micromolding the microelectrode shank, post molding machining, sacrificial release of the microelectrode and electrodeposition of iridium oxide onto the microelectrode sites. Electrode site position accuracy was shown to have a standard deviation of less than 4 MUm. Acute in vivo recordings with the 32-channel shank microelectrode array demonstrated comparable performance to that obtained with commercial microelectrode arrays. This new approach to microelectrode array fabrication will enable new microelectrodes, such as multi-sided arrays, drug eluding electrodes and biodegradable shanks. PMID- 21979568 TI - Epidemiological investigation and genome analysis of duck circovirus in Southern China. AB - Duck circovirus (DuCV), a potential immunosuppressive virus, was investigated in Southern China from March 2006 to December 2009 by using a polymerase chain reaction (PCR) based method. In this study, a total of 138 sick or dead duck samples from 18 different farms were examined with an average DuCV infection rate of ~35%. It was found that ducks between the ages of 40~60 days were more susceptible to DuCV. There was no evidence showing that the DuCV virus was capable of vertical transmission. Farms with positive PCR results exhibited no regularly apparent clinical abnormalities such as feathering disorders, growth retardation or lower-than-average weight. The complete genomes of 9 strains from Fujian Province and 1 from Zhejiang Province were sequenced and analyzed. The 10 DuCV genomes, compared with others genomes downloaded from GenBank, ranged in size from 1988 to 1996 base pairs, with sequence identities ranging from 83.2% to 99.8%. Phylogenetic analysis based on genome sequences demonstrated that DuCVs can be divided into two distinct genetic genotypes, Group I (the Euro-USA lineage) and Group II (the Taiwan lineage), with approximately 10.0% genetic difference between the two types. Molecular epidemiological data suggest there is no obvious difference among DuCV strains isolated from different geographic locations or different species, including Duck, Muscovy duck, Mule duck, Cheery duck, Mulard duck and Pekin duck. PMID- 21979569 TI - Susceptibility to AcMNPV and expression of recombinant proteins by a novel cell clone derived from a Trichoplusia ni QAU-BTI-Tn9-4s cell line. AB - It is well known that Tn5B1-4 (commercially known as the High Five) cell line is highly susceptible to baculovirus and provides superior production of recombinant proteins when compared to other insect cell lines. But the characteristics of the cell line do not always remain stable and may change upon continuous passage. Recently an alphanodavirus, named Tn5 Cell Line Virus (or TNCL Virus), was identified in High Five cells in particular. Therefore, we established a new cell line, QB-Tn9-4s, from Trichoplusia ni, which was determined to be free of TNCL virus by RT-PCR analysis. In this paper, we describe the development of a novel cell clone, QB-CL-B, from a low passage QB-Tn9-4s cell line and report its susceptibility to AcMNPV, and the level of recombinant protein production. This cell clone was similar to its parental cells QB-Tn9-4s and Tn5B1-4 cells in morphology and growth rate; although it also showed approximately the same responses to AcMNPV infection and production of occlusion bodies, there were higher levels of recombinant protein production in comparison to QB-Tn9-4s (parental cells) and High5 cells. PMID- 21979570 TI - Comparison of influenza outbreaks in the Republic of Kazakhstan and Russia induced by 2009 yearly new variant of A(H1N1) influenza virus. AB - The aim of the work is the comparison of the epidemiology of influenza and acute respiratory virus infections (ARVI) in the Republic of Kazakhstan with the corresponding influenza epidemic in Russia induced by influenza pandemic virus A/California/07/2009 in 2009. Data on influenza and ARVI from the Republic of Kazakhstan and Federal Center of influenza was collected and investigated over the course of several weeks from hospitalized patients with the same diagnosis among all population and in age groups on 16 territories of Kazakhstan and in 49 major cities of Russia. The epidemic in Kazakhstan resembled the Russian epidemic in terms of its abnormally early beginning, expression of monoaetiology, the spread of the epidemic into all territories and start of the epidemics among adult population. High percentage of hospitalized people and lethal outcome were registered in this epidemic. Similarity of epidemic process character in corresponding border-line territories of both countries was found out. PMID- 21979571 TI - A new indicator cell line established to monitor bovine foamy virus infection. AB - In order to improve the accuracy for quantitating the bovine foamy virus (BFV) in vitro, we developed a baby hamster kidney cell (BHK)-21-derived indicator cell line containing a plasmid that encodes the firefly luciferase driven by the BFV long terminal repeat promoter (LTR, from -7 to 1012). The BFV titer could be determined by detecting the luciferase expression since the viral trans-activator BTas protein activates the promoter activity of the LTR. One clone, designated BFVL, was selected from ten neomycin-resistant clones. BFVL showed a specific and inducible dose- and time-dependent luciferase activity in response to BFV infection. Although the changes in luciferase activity of BFVL peaked at 84 h post infection, it was possible to differentiate infected and uninfected cells at 48 h post infection. A linear relationship was established between the multiplicity of infection (MOI) of BFV and the activated ratio of luciferase expression in BFVL. Moreover, the sensitivity of the BFVL-based assay for detecting infectious BFV was 10,000 times higher than the conventional CPE-based assay at 48 h post infection. These findings suggest that the BFVL-based assay is rapid, easy, sensitive, quantitative and specific for detection of BFV infection. PMID- 21979572 TI - Evaluation of efficacy of stabilizers on the thermostability of live attenuated thermo-adapted Peste des petits ruminants vaccines. AB - In this study, thermo-adapted (Ta) PPR vaccines were assessed for their stability at 25, 37, 40, 42 and 45 degrees C in lyophilized form using two extrinsic stabilizers {lactalbumin hydrolysate-sucrose (LS) and stabilizer E} and in reconstituted form with the diluents (1 mol/L MgSO(4) or 0.85% NaCl). The lyophilized vaccines showed an expiry period of 24-26 days at 25 degrees C, 7-8 days at 37 degrees C and 3-4 days at 40 degrees C. LS stabilizer was superior at 42 degrees C with a shelf-life of 44 h, whereas in stabilizer E, a 40 h shelf life with a comparable half-life was observed. At 45 degrees C, the half-life in stabilizer E was better than LS and lasted for 1 day. Furthermore, the reconstituted vaccine maintained the titre for 48 h both at 4 degrees C and 25 degrees C and for 24-30 h at 37 degrees C. As both the stabilizers performed equally well with regard to shelf-life and half-life, the present study suggests LS as stabilizer as a choice for lyophilization with 0.85% NaCl diluent, because it has better performance at higher temperature. These Ta vaccines can be used as alternatives to existing vaccines for the control of the disease in tropical countries as they are effective in avoiding vaccination failure due to the breakdown in cold-chain maintenance, as this vaccine is considerably more stable at ambient temperatures. PMID- 21979573 TI - Production of CCHF virus-like particle by a baculovirus-insect cell expression system. AB - Crimean-Congo Haemorrhagic Fever Virus (CCHFV) is a tick-born virus of the Nairovirus genus within the Bunyaviridae family, which is widespread and causes high fatality. The nucleocapsid of CCHFV is comprised of N proteins that are encoded by the S segment. In this research, the N protein of CCHFV was expressed in insect cells using a recombinant baculovirus. Under an electron microscope, Virus-Like Particles (VLPs) with various size and morphology were observed in cytoplasmic vesicles in the infected cells. Sucrose-gradient purification of the cell lysate indicated that the VLPs were mainly located in the upper fraction after ultracentrifugation, which was confirmed by Western blot analysis and immuno-electron microscopy (IEM). PMID- 21979574 TI - Molecular determinants responsible for the subcellular localization of HSV-1 UL4 protein. AB - The function of the herpes simplex virus type 1 (HSV-1) UL4 protein is still elusive. Our objective is to investigate the subcellular transport mechanism of the UL4 protein. In this study, fluorescence microscopy was employed to investigate the subcellular localization of UL4 and characterize the transport mechanism in living cells. By constructing a series of deletion mutants fused with enhanced yellow fluorescent protein (EYFP), the nuclear export signals (NES) of UL4 were for the first time mapped to amino acid residues 178 to 186. In addition, the N-terminal 19 amino acids are identified to be required for the granule-like cytoplasmic pattern of UL4. Furthermore, the UL4 protein was demonstrated to be exported to the cytoplasm through the NES in a chromosomal region maintenance 1 (CRM1)-dependent manner involving RanGTP hydrolysis. PMID- 21979575 TI - The molecular recognition of phosphorylated proteins by designed polypeptides conjugated to a small molecule that binds phosphate. AB - The conjugation of polypeptides from a designed set to the small molecule ligand 3,5-bis[[bis(2-pyridylmethyl)amino]methyl]benzoic acid, which in the presence of Zn(2+) ions binds inorganic phosphate, has been shown to provide a polypeptide conjugate that binds alpha-casein, a multiply phosphorylated protein, with a dissociation constant K(D) of 17 nM. The measured affinity is more than three orders of magnitude higher than that of the small molecule ligand for phosphate and the binding of 500 nM of alpha-casein was not inhibited by 10 mM phosphate buffer, providing a 2000-fold excess of phosphate ion over protein. The selectivity for phosphoproteins was demonstrated by extraction of alpha-casein from solutions of various complexity, including milk and human serum spiked with alpha-casein. In addition to alpha-casein, beta-casein was also recognized but not ovoalbumin. Conjugation of a polypeptide to the zinc chelating ligand was therefore shown to give rise to dramatically increased affinity and also increased selectivity. A set of polypeptide conjugates is expected to be able to capture a large number of phosphorylated proteins, perhaps all, and in combination with electrophoresis or mass spectrometry become a powerful tool for the monitoring of phosphorylation levels. The presented binder can easily be attached to various types of surfaces; here demonstrated for the case of polystyrene particles. The example of phosphoproteins was selected since posttranslational phosphorylation is of fundamental importance in cell biology due to its role in signaling and therefore of great interest in drug development. The reported concept for binder development is, however, quite general and high affinity binders can conveniently be developed for a variety of proteins including those with posttranslational modifications for which small molecule recognition elements are available. PMID- 21979577 TI - Temperature-related effects of adenosine triphosphate-activated microglia on pro inflammatory factors. AB - BACKGROUND: Therapeutic hypothermia protects neurons after severe brain injury. Activated microglia produce several neurotoxic factors, such as pro-inflammatory cytokines and nitric oxide (NO), during neuron destruction. Hence, suppression of microglial release of these factors is thought to contribute partly to the neuroprotective effects of hypothermia. After brain insults, adenosine triphosphate (ATP) is released from injured cells and activates microglia. Here, we examined the acute effects of temperature on ATP-activated microglial production of inflammatory factors, and the possible involvement of p38 mitogen activated protein kinase (p38) underlying such effects. METHODS: Microglia were cultured with ATP at 33, 37, and 39 degrees C, or with ATP in the presence of a p38 inhibitor, SB203580, at 37 degrees C. Cytokine and NO levels, and p38 activation were measured. RESULTS: Compared to 37 degrees C, TNF-alpha was reduced at 33 degrees C and augmented at 39 degrees C for 1.5 h. IL-6 was reduced at 33 degrees C for 6 h. NO was reduced at 33 degrees C, but augmented at 39 degrees C for 6 h. p38 was reduced at 33 degrees C for 1 min. SB203580 inhibited ATP-induced TNF-alpha, IL-6, and NO production. CONCLUSION: Lowering temperature rapidly reduced p38 activation and the subsequent p38-regulated production of pro inflammatory cytokines and NO in ATP-activated microglia, suggesting that attenuation of early phase inflammatory responses via suppression of p38 in microglia is one possible neuroprotective mechanism of therapeutic hypothermia. Temperature elevation increased TNF-alpha and NO production in these cells. These temperature-dependent changes imply that monitoring of TNF-alpha and NO in the cerebrospinal fluid during the early phase might be useful as biomarkers for responses to therapeutic hypothermia and hyperthermia. PMID- 21979578 TI - Gene-viro-therapy targeting liver cancer by a dual-regulated oncolytic adenoviral vector harboring IL-24 and TRAIL. AB - Cancer-targeting gene-viro-therapy is a promising cancer therapeutic strategy that strengthens the antitumor effect of oncolytic viruses by expressing an inserted foreign antitumor gene. To achieve liver cancer targeting and to improve the safety of the ZD55 vector (a widely-used E1B55KD gene-deleted oncolytic adenoviral vector (OV), we previously constructed), we designed a novel OV named Ad.AFP.D55 that selectively replicates in hepatocellular carcinoma (HCC) cells by replacing the E1A promoter with the liver-cancer specific alpha-Fetoprotein (AFP) promoter based on the ZD55 vector. We found that the oncolytic adenoviruses Ad.AFP.D55-IL-24 and Ad.AFP.D55-TRAIL express tumor-suppressor gene interleukin 24 (IL-24) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), respectively, significantly suppressed the HCC cell growth in vitro by inducing apoptosis by the caspase-8 and mitochondria-dependent caspase-9 signaling pathways. Furthermore, the combined treatment of Ad.AFP.D55-IL-24 and Ad.AFP.D55 TRAIL showed strong antitumor effects in vivo by significantly inhibiting the tumor growth in HCC HuH-7 cell xenograft mice, and markedly increasing animal survival rate. Therefore, this novel HCC cell-targeting OV carrying tumor suppressor genes may provide a promising approach for liver cancer gene therapy. PMID- 21979579 TI - Retargeting NK92 cells using an HLA-A2-restricted, EBNA3C-specific chimeric antigen receptor. AB - Advances in adoptive cell immunotherapy have led to several promising options for cancer patients. Single-chain variable fragments (scFvs) were isolated from a human phage display library by panning on recombinant human leukocyte antigen (HLA)-A2-peptide complexes. A scFv (EBNA Clone 315) specific for HLA-A2 carrying a 10 amino acid peptide (LLDFVRFMGV) derived from the Epstein-Barr virus latent protein EBNA3C was fully characterized. EBNA Clone 315 displayed exquisite specificity toward its targeted T-cell epitope (TCE) and did not cross-react with the free peptide, HLA-A2 complexes, which carried irrelevant peptides, or HLA-A2( ) cells. Furthermore, after engineering into a scFv-Fc fusion protein, we were able to determine its affinity, detection sensitivity, and ability to induce antibody-dependent cellular cytotoxicity (ADCC). As a proof-of-principle, a chimeric antigen receptor (CAR) version of EBNA Clone 315 was used to reprogram NK92MI cells. CAR-expressing NK92MI cells showed highly specific and potent cytotoxicity toward the targeted TCE, with detection sensitivity of approximately 25 molecules and cytolytic capacity threefold greater than scFv-Fc-mediated ADCC. For the first time, we show the successful reprogramming of non-T cells toward a specific TCE using a CAR. PMID- 21979580 TI - Plant extracellular ATP signalling: new insight from proteomics. AB - Complex signalling systems have evolved in multicellular organisms to enable cell to-cell communication during growth and development. In plants, cell communication via the extracellular matrix (apoplast) controls many processes vital for plant survival. Secretion of ATP into the extracellular matrix is now recognised as a previously unknown stimulus for cell signalling with a role in many aspects of plant physiology. In the last decade, the secondary messenger molecules in extracellular ATP signalling were identified, but the downstream gene and protein networks that underpin plant responses to extracellular ATP are only beginning to be characterised. Here we review the current status of our knowledge of plant extracellular signalling and demonstrate how applying state-of the art proteomic technologies is rapidly bringing new discoveries in extracellular ATP research. We discuss how monitoring of the global proteomic profile during responses to modulation of extracellular ATP signalling has led to novel insight into pathogen defence systems and plant programmed cell death regulation. On the basis of extensive proteomic, pharmacological, and reverse genetics data, extracellular ATP has been confirmed to constitute an important molecular switch that tightly controls organellar energy metabolism, reprogramming of primary metabolic pathways, and redirection of resources to protein networks that support adaptation of plants to stress. PMID- 21979581 TI - Molecular characterization of endo-1,3-beta-glucanase from Cellulosimicrobium cellulans: effects of carbohydrate-binding module on enzymatic function and stability. AB - An endo-1,3-beta-glucanase was purified from Tunicase(r), a crude enzyme preparation from Cellulosimicrobium cellulans DK-1, and determined to be a 383 residue protein (Ala1-Leu383), comprising a catalytic domain of the glycoside hydrolase family 16 and a C-terminal carbohydrate-binding module family 13. The Escherichia coli expression system of the catalytic domain (Ala1-Thr256) was constructed, and the protein with N-terminal polyhistidine tag was purified using a Ni-nitrilotriacetic acid column. We analyzed enzymatic properties of the recombinant catalytic domain, its variants, and the Tunicase(r)-derived full length endo-1,3-beta-glucanase. Substitution of Glu119 with Ala and deletion of Met123, both of the residues are located in the catalytic motif, resulted in the loss of hydrolytic activity. In comparison between the full-length enzyme and isolated catalytic domain, their hydrolytic activities for soluble substrates such as laminarin and laminarioligosaccharides were similar. In contrast, the hydrolytic activity of the full-length enzyme for insoluble substrates such as curdlan and yeast-glucan was significantly higher than that of the catalytic domain. It should be noted that the acid stabilities for the hydrolysis of laminarin were clearly different. Secondary structure analysis using circular dichroism showed that the full-length enzyme was more acid stable than was the catalytic domain, possibly because of domain interactions between the catalytic domain and the carbohydrate-binding module. PMID- 21979583 TI - The crystal structure of ADP-L-glycero-D-manno-heptose-6-epimerase (HP0859) from Helicobacter pylori. AB - Helicobacter pylori, the human pathogen that affects about half of the world population and that is responsible for gastritis, gastric ulcer and adenocarcinoma and MALT lymphoma, owes much of the integrity of its outer membrane on lipopolysaccharides (LPSs). Together with their essential structural role, LPSs contribute to the bacterial adherence properties, as well as they are well characterized for the capability to modulate the immuno-response. In H. pylori the core oligosaccharide, one of the three main domains of LPSs, shows a peculiar structure in the branching organization of the repeating units, which displayed further variability when different strains have been compared. We present here the crystal structure of ADP-L-glycero-D-manno-heptose-6-epimerase (HP0859, rfaD), the last enzyme in the pathway that produces L-glycero-D-manno heptose starting from sedoheptulose-7-phosphate, a crucial compound in the synthesis of the core oligosaccharide. In a recent study, a HP0859 knockout mutant has been characterized, demonstrating a severe loss of lipopolysaccharide structure and a significant reduction of adhesion levels in an infection model to AGS cells, if compared with the wild type strain, in good agreement with its enzymatic role. The crystal structure reveals that the enzyme is a homo-pentamer, and NAD is bound as a cofactor in a highly conserved pocket. The substrate binding site of the enzyme is very similar to that of its orthologue in Escherichia coli, suggesting also a similar catalytic mechanism. PMID- 21979582 TI - Conformation-dependent scFv antibodies specifically recognize the oligomers assembled from various amyloids and show colocalization of amyloid fibrils with oligomers in patients with amyloidoses. AB - Increasing evidence indicates that amyloid aggregates, including oligomers, protofibrils or fibrils, are pivotal toxins in the pathogenesis of many amyloidoses such as Alzheimer's disease (AD), Parkinson's disease, Huntington's disease, prion-related diseases, type 2 diabetes and hereditary renal amyloidosis. Various oligomers assembled from different amyloid proteins share common structures and epitopes. Here we present data indicating that two oligomer specific single chain variable fragment (scFv) antibodies isolated from a naive human scFv library could conformation-dependently recognize oligomers assembled from alpha-synuclein, amylin, insulin, Abeta1-40, prion peptide 106-126 and lysozyme, and fibrils from lysozyme. Further investigation showed that both scFvs inhibited the fibrillization of alpha-synuclein, amylin, insulin, Abeta1-40 and prion peptide 106-126, and disaggregated their preformed fibrils. However, they both promoted the aggregation of lysozyme. Nevertheless, the two scFv antibodies could attenuate the cytotoxicity of all amyloids tested. Moreover, the scFvs recognized the amyloid oligomers in all types of plaques, Lewy bodies and amylin deposits in the brain tissues of AD and PD patients and the pancreas of type 2 diabetes patients respectively, and showed that most amyloid fibril deposits were colocalized with oligomers in the tissues. Such conformation-dependent scFv antibodies may have potential application in the investigation of aggregate structures, the mechanisms of aggregation and cytotoxicity of various amyloids, and in the development of diagnostic and therapeutic reagents for many amyloidoses. PMID- 21979584 TI - Evidence-based selective application of transhiatal esophagectomy in a high volume esophageal center. AB - BACKGROUND: Transthoracic esophagectomy (TTE) with lymphadenectomy represents the gold standard of operative approaches to esophageal cancer. The TTE procedure carries significant operative risk, particularly in patients with co-morbidities, and the possible oncologic benefit of a mediastinal lymph node dissection in certain subgroups of patients with esophageal cancer is controversial. Transhiatal esophagectomy (THE), which avoids a thoracotomy, may reduce morbidity and mortality below levels seen with TTE, and there is no proof from randomized studies of any oncologic inferiority to TTE in patients with early tumors. Accordingly, the selective use of THE has increased in our high-volume center in recent years, and this study audits that experience over the last decade METHODS: Between 2000 and 2009 inclusive, 584 patients were treated surgically with curative intent. The standard operative approach in our unit is en bloc TTE, and THE represents 5.5% overall, and 11.1% in the second 5-year period (2004-2009), compared with 2% previously. The present study details the selection of these cases (n = 32) treated with THE and their outcomes, as well as the outcomes in the TTE (n = 438) group RESULT: Transhiatal esophagectomy was used for early stage carcinoma (n = 18) and for patients of advanced age who also had co morbidities (n = 14). Patients undergoing THE were significantly older (68.46 versus 63.07 years of age; p = 0.002), and were at higher operative risk based on ASA grade (grade 3: 53.1% versus 17.3%; p < 0.001), compared with TTE patients. The THE cohort also included more patients with early cancers compared with the TTE cohort (56.3% versus 17.6%; p < 0.001). There were no differences in R0 resection rates for patients with early tumors or advanced co-morbidity. Nodal yields were lower in THE patients (p = 0.005). The overall complication rate was lower in the THE group (31.6% versus 44.2%; p = 0.021), and there were no postoperative deaths in the transhiatal group, whereas the in-hospital mortality rate for the TTE group was 3% (p < 0.001). Disease-specific survival was equivalent with each approach. CONCLUSIONS: Transhiatal esophagectomy has a role in a pragmatic individualized approach to esophageal cancer. As an alternative to a standardized en bloc transthoracic esophagectomy, the transhiatal approach may be suitable for patients with predicted node-negative cancers or those with resectable disease who are not candidates for TTE because of co-morbidity. PMID- 21979585 TI - Ovarian serous carcinoma: relationship of p53 and bcl-2 with tumor angiogenesis and VEGF expression. AB - The aim of the study was to assess the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression in ovarian serous carcinoma and to examine their relation with apoptosis.Paraffin-embedded specimens of 41 cases of ovarian serous carcinomas were evaluated by immunohistochemistry for VEGF, p53, and bcl-2 expression. MVD was assessed with CD31 staining. We investigated the association of tumor angiogenesis (MVD and VEGF) with clinicopathologic factors, p53 overexpression, and bcl-2 expression.There was a significant correlation between high MVD and suboptimal debulking and advanced stage disease. A significant negative correlation was expressed between bcl-2 and VEGF expression. In univariate analysis, only stage had a significant impact on disease-free survival.The results of this study suggest that higher degree of angiogenesis is associated with suboptimal debulking and advanced-stage disease. Expression of VEGF had negative association with VEGF expression. PMID- 21979586 TI - Clinical relevance of TAp73 and DeltaNp73 protein expression in ovarian cancer: a series of 83 cases and review of the literature. AB - The p73 gene gives rise to the full-length transactivation competent TAp73 and the N-terminally truncated isoform DeltaNp73, which inhibits TAp73 and wild-type p53. The clinical relevance of TAp73 and DeltaNp73 protein expression has not yet been evaluated in ovarian cancer. TAp73 and DeltaNp73 expression was examined using immunohistochemistry and reverse transcription-polymerase chain reaction in 83 and 64 ovarian cancer specimens, respectively. A yeast-based assay and subsequent sequencing were performed to analyze the p53 mutational status. TAp73 and DeltaNp73 protein expression was found in 73 of 83 (88%) and 48 of 83 (57.8%) ovarian cancer samples, respectively. The majority of cases showed immunostaining in both the nucleus and cytoplasm of tumor cells. TAp73 and DeltaNp73 protein expression correlated with messenger RNA quantification in 25 of 64 (39.1%) and 37 of 64 (57.8%) cancer specimens, respectively. TAp73 and DeltaNp73 protein expression was not associated with the p53 mutational status, clinicopathologic parameters, and prognosis of the examined ovarian cancer cases. Although TAp73 and DeltaNp73 protein expression did not possess prognostic significance for ovarian cancer in this study, a potential clinical role of p73 isoforms cannot be definitively excluded due to limitations of immunohistochemistry. PMID- 21979587 TI - Metaplastic papillary tumor of the salpinx: report of a case using microsatellite analysis. AB - Metaplastic papillary tumor (MPT) of the salpinx is a rare lesion found in the lumen of fallopian tubes during the postpartum period. This lesion is very small and is composed microscopically of papillae lined by stratified epithelium. Similar to serous borderline ovarian tumors (BOTs), epithelial elements of MPT show a budding, abundant, dense, and eosinophilic cytoplasm, bland nuclei or with mild atypia. It is not clear whether this lesion is a papillary metaplastic proliferation or a small atypical proliferative (borderline) serous tumor associated with pregnancy. Owing to its rarity, MPT has never been investigated in molecular studies and compared with ovarian serous neoplasms. In this study, a case of tubal MPT was molecularly examined and compared with 4 BOTs and with 2 low-grade ovarian carcinomas, using microsatellite analysis with 13 markers at 8 chromosomal regions involved in ovarian carcinogenesis. The tubal MPT and one of the BOTs showed no alterations in the investigated chromosomal regions. The remaining 3 BOTs showed only single allelic imbalances. Instead, low-grade serous carcinomas showed a higher frequency of alterations, including allelic imbalance at chr10q23, 1p36, 9p22, and 17. In conclusion, this study provides, for the first time, molecular data on an MPT of the fallopian tube, indicating that this entity might share both morphologic and molecular similarities with a subset of minimally altered BOTs, termed atypical proliferative serous tumors, which behave in a benign manner. However, in our opinion, further molecular studies should be conducted on other cases of MPTs to confirm this hypothesis. PMID- 21979588 TI - Anti-Yo antibody associated with occult fallopian tube carcinoma. AB - This is the case report of a 61-year-old woman who presented with progressive diplopia and ataxia. Her cerebrospinal fluid revealed high titers of anti-Yo (PCA 1) antibody and a magnetic resonance imaging with contrast showed cerebellar degeneration. Extensive imaging workup was negative for malignancy and she was otherwise asymptomatic. Given the association between anti-Yo antibodies and gynecologic malignancies, she underwent a bilateral salpingo-oophorectomy and cancer staging. Extensive section of the fimbriated end of the fallopian tube revealed a stage 1, microscopic serous adenocarcinoma. After surgery, her anti-YO titers fell and plans were made for adjuvant chemotherapy. Her neurologic symptoms are not expected to substantially improve, illustrating the urgent need for early surgical investigation in cases of paraneoplastic syndrome, even in the absence of imaging evidence of a lesion. PMID- 21979589 TI - Extrapancreatic solid pseudopapillary neoplasm: report of a case of primary ovarian origin and review of the literature. AB - Solid pseudopapillary neoplasm, an uncommon, intriguing, low-grade malignant tumor of the pancreas, can exceptionally occur in extrapancreatic sites. We report 1 such case occurring as an ovarian primary in a 25-year-old woman, who presented with abdominal fullness. She remained well 12 years after resection of the 1.7-kg right ovarian tumor. Histologically, the tumor showed a solid, dehiscent, and pseudopapillary growth, traversed by fibrous septa and arborizing blood vessels. The polygonal tumor cells had round nuclei, fine chromatin, and lightly eosinophilic granular cytoplasm. In certain areas, eosinophilic hyaline globules were present. On immunostaining, the tumor cells were positive for beta catenin (nuclear translocation), CD10, CD56, and synaptophysin (focal), and were negative for cytokeratin, E-cadherin, and chromogranin. The morphologic and immunohistochemical features were compatible with those of solid pseudopapillary neoplasm. Review of the literature uncovered 10 cases of extrapancreatic solid pseudopapillary neoplasm with adequate data for analysis. They were seen to occur predominantly in young female patients, who presented with a large tumor mass, similar to their pancreatic counterparts. The most common sites of occurrence were the mesocolon (with ectopic pancreatic tissue) and ovary. Awareness of the existence of this tumor in various extrapancreatic sites is essential to avoid misdiagnosis. PMID- 21979590 TI - Origin of uterine teratoma differs from that of ovarian teratoma: a case of uterine mature cystic teratoma. AB - Mature cystic teratomas are usually found in the ovaries and rarely in the uterus. Most teratomas of the uterus are of cervical origin. There are only a handful of reports to date of uterine teratomas arising from uterine corpus. The teratomas of the ovaries and the cervix are thought to be of parthenogenetic origin from oocyte after the completion of the first division. However, the origin of a uterine teratoma has not been established by molecular methods. In this study, we report a 46-year-old woman with a teratoma within uterine corpus. Computed tomography scanning and histological studies after tumor resection confirmed the diagnosis of teratoma. The DNA profiles of normal uterine tissue and teratoma tissue were compared using short tandem repeats analysis and showed that the teratoma did not originate from the parthenogenetic process. Our results suggest that the origin of this uterine teratoma is most likely pluripotential stem cell of uterus or primordial germ cell before meiosis I. PMID- 21979591 TI - An unusual case of adult filarial oophoritis. AB - Ovaries are the least involved site of infection in the female genital tract. Parasitic infestations of the ovary are even rarer. We report an unusual case of adult filariasis of the ovary discovered incidentally on histopathologic examination. Panhysterectomy was performed on a 47-year-old north Indian woman with multiple uterine fibroids, where menorrhagia was unresponsive to hormonal therapy. An adult nongravid female filarial worm was identified in the dilated ovarian lymphatic system. The host local immune response was minimal. Subsequent work-up failed to show any physical stigmata or diagnostic evidence of the disease. The structural details of the adult worm are characteristic to permit its recognition on histologic examination. The involvement of an adult worm in the female genital tract is distinctly uncommon in comparison with the male genital involvement. Till date, only a handful of cases of ovarian adult filariasis are reported. PMID- 21979593 TI - Immunoexpression of PAX 8 in endometrial cancer: relation to high-grade carcinoma and p53. AB - PAX 8 is a crucial transcription factor for organogenesis of the thyroid gland, kidney, and the Mullerian system and plays an essential role in cell proliferation. The purpose of this study was to evaluate the association between p53 and PAX 8 expression and the clinical value of PAX 8 in endometrial carcinoma. We detected 106 consecutive patients with primary endometrial carcinoma (type I/ endometrioid, n=84; type II/ nonendometrioid, n=20; rare subtypes, n=2) who were treated at our institution between 1999 and 2009. Of the 106 patients, 97 cases were eligible for further investigations. PAX 8 and p53 expression were assessed using immunohistochemistry from paraffin-embedded tissue blocks. Results were correlated with clinical data. PAX 8 immunoreaction was found in 70 of 97 (72.1%) patients, including 56 of 77 (72.7%) endometrioid carcinomas and 13 of 18 (72.2%) type II carcinomas. A positive correlation was observed between PAX 8 and p53 expression (P=0.0005), histologic type (P=0.04), and histologic grade (P=0.02). No association was found between PAX 8 expression and tumor stage, vascular space involvement, lymph node involvement, and age of the patients. Furthermore, using univariate and multivariate analyses, no statistically significant relationship could be evaluated between patient survival data and PAX 8 expression. PAX 8 is expressed in the vast majority of endometrial carcinomas both of endometrioid and nonendometrioid type. PAX 8 overexpression correlates with p53 expression and high-grade endometrial carcinomas but seems not to be useful as a prognostic parameter. PMID- 21979594 TI - Carcinosarcoma arising in a uterine leiomyoma: report of a unique neoplasm. AB - Malignant transformation of a uterine leiomyoma is an exceedingly rare phenomenon. Previous reported examples of malignant neoplasms to arise so include leiomyosarcoma, angiosarcoma, and malignant mesenchymoma. We report an intramural carcinosarcoma arising in a uterine leiomyoma in a 38-year-old woman. This case is unique in being the first recorded carcinosarcoma arising within a uterine leiomyoma and the first example of an epithelial neoplasm to do so. We discuss the differential diagnosis and possible pathogenesis of the tumor that has likely arisen secondary to epitheliogenesis in a mesenchymal neoplasm. PMID- 21979595 TI - Subinvolution of the placental site 6 years after last delivery. PMID- 21979592 TI - Endometriosis and ovarian cancer: a review of clinical, pathologic, and molecular aspects. AB - Endometriosis is a chronic disease that affects millions of reproductive-age women. Despite the destructive and invasive nature of endometrioses, most cases are perpetually benign or eventually regress; however, atypical endometriosis is a precursor lesion and can lead to certain types of ovarian cancer. Endometriosis induced inflammation and auto- and paracrine production of sex steroid hormones contribute to ovarian tumorigenesis. These changes provide microenvironment necessary to accumulate enough genetic alterations for endometriosis associated malignant transformation. It takes years for endometriosis to undergo the pathophysiological progression that begins with atypical epithelial proliferation (atypical endometriosis and metaplasia), and then is followed by the formation of well-defined borderline tumors, and finally culminates in fully malignant ovarian cancer. This study is a review of the natural history of endometriosis and the role of microenvironments that favor the accumulation of genetic alterations and endometriosis-associated ovarian cancer progression. PMID- 21979596 TI - immunohistochemical expression of survivin and gamma-H2AX in vulvar intraepithelial neoplasia and low-stage squamous cell carcinoma. AB - Survivin inhibits apoptosis and is involved in the regulation of cell cycle progression and in the mitotic spindle formation. It is overexpressed in many cancers. The histone gamma-H2AX is a marker of activated DNA damage and is overexpressed in different cancers and their precursor lesions. It also forms early during apoptosis. Eighty-seven formalin-fixed, paraffin-embedded archival vulvar tissues originating from 55 preoperatively untreated patients were immunostained with antibodies to survivin and gamma-H2AX to determine their expression in normal squamous vulvar epithelia (NE, n=25), lichen sclerosus (n=10), high-grade classic vulvar intraepithelial neoplasia (n=16), differentiated vulvar intraepithelial neoplasia (n=16), and vulvar invasive keratinizing squamous cell carcinoma (ISCC, n=20; FIGO Ib). Immunostaining for both factors was scored for moderate and strong intensities with regard to quantity. Statistical analysis was performed by the chi test and Fisher exact test. Nuclear surviving expression increased from NE and lichen scleros to high grade classic vulvar intraepithelial neoplasia, differentiated vulvar intraepithelial neoplasia, and ISCC significantly (P=0.0001) and followed the distribution of immature squamous epithelial cells. Positive scores for gamma H2AX were found in nuclei of cells in all diagnostic cohorts, in any epithelial level with some accentuation in the upper layers, was seen in pycnotic nuclei in horn pearls of ISCC and apoptotic bodies, without relevant statistical distributions. Immunoscores did not differ between grade 1 and grades 2/3. Expression patterns were different for both factors, suggesting their involvement in different biologic mechanisms as an early event leading to resistance to apoptosis in vulvar carcinogenesis. PMID- 21979597 TI - Subtype distribution of human papillomavirus in HIV-infected women with cervical intraepithelial neoplasia stages 2 and 3 in Botswana. AB - Human papillomavirus (HPV) vaccines containing types 16 and 18 are likely to be effective in preventing cervical cancer associated with these HPV types. No information currently exists in Botswana concerning the HPV types causing precancerous or cancerous lesions. Our goal was to determine the prevalence of HPV types associated with precancerous cervical intraepithelial neoplasia (CIN) stages 2 and 3 in HIV-infected women in Gaborone, Botswana. HIV-infected women referred to our clinic with high-grade intraepithelial lesion on the Pap smear were enrolled in the study. HPV typing was only performed if the histopathology results showed CIN stage 2 or 3 disease using linear array genotyping (CE-IVD, Roche Diagnostics). One hundred HIV-infected women were identified with CIN stages 2 or 3 between August 11, 2009 and September 29, 2010. Eighty-two of 100 women enrolled had coinfection by multiple HPV subtypes (range, 2 to 12). Of the remaining 18 women, 14 were infected with a single high-risk subtype and 4 had no HPV detected. Overall, 92 (92%) women were infected with at least 1 high-risk HPV subtype, and 56 were coinfected with more than 1 high-risk HPV type (range, 2 to 5). Fifty-one (51%) women had HPV subtypes 16, 18, or both. HPV 16 and 18 are the most common types in HIV-infected women with CIN 2 or 3 in Gaborone, Botswana, suggesting that the implementation of HPV vaccination programs could have a significant impact on the reduction of cervical cancer incidence. However, given the relative lack of knowledge on the natural history of cervical cancer in HIV infected women and the significant prevalence of infection and coinfection with other high-risk HPV types in our sample, the true impact and cost-effectiveness of such vaccination programs need to be evaluated. PMID- 21979598 TI - Diagnostic implications of L1, p16, and Ki-67 proteins and HPV DNA in low-grade cervical intraepithelial neoplasia. AB - The expressions of p16, Ki-67, and L1 proteins and human papillomavirus DNA were investigated using polymerase chain reaction (HPV/PCR) and catalyzed signal amplified colorimetric DNA in situ hybridization (CSAC/ISH) as potential molecular markers for the diagnosis and transforming potential of low cervical intraepithelial neoplasia (CIN1). Ki-67 and p16 protein expression increased linearly from control cases to more dysplastic cases (CIN1, CIN2, and CIN3), peaking in squamous cell carcinoma cases (P<0.05). In contrast, L1 expression was inversely correlated with malignant transformation. Patients with CIN1 were divided into 4 groups: L1p16, L1p16, L1p16, and L1p16, and the immunohistochemical results were combined with HPV/PCR, L1/PCR, and high-risk E6/E7 genome and CSAC/ISH data. Malignant transformation correlated with L1p16 patients (100% of CIN2, CIN3, and squamous cell carcinoma cases) and was evident in approximately 23% of CIN1 cases. In addition, the presence of HPV/DNA was evident in 52% of CIN1 cases, and within the L1p16 group. In 4 of 7 cases, the high-risk E6/E7 HPV genome was present and in 1 case it was integrated into the host DNA, as confirmed using CSAC/ISH. In patients with CIN1, investigating the presence of HPV/DNA using PCR and the presence of the high-risk E6/E7 genome is necessary to distinguish high-risk oncogenic patient groups from low-risk groups. This study highlights the importance of combining immunohistochemical analysis with HPV/PCR and CSAC/ISH to identify patients with CIN1 with a risk of neoplastic progression. PMID- 21979599 TI - Misplaced Skene's glands: glandular elements in the lower female genital tract that are variably immunoreactive with prostate markers and that encompass vaginal tubulosquamous polyp and cervical ectopic prostatic tissue. AB - So-called ectopic prostatic tissue in the cervix and vaginal tubulosquamous polyps are rare morphologically similar lesions that may show positive immunohistochemical staining with prostatic markers. It has been suggested that they are related to paraurethral Skene's glands that are the female equivalent of prostatic glands in the male. We report a large series of lesions in women aged 23 to 81 years, found within the cervix (n=24), vagina (n=10), and vulva (n=2), which we believe to be a part of a spectrum of lesions derived from Skene's glands, either eutopic or more commonly misplaced during embryonic development. In all cervical cases, the lesion was predominantly situated in the ectocervix and was an incidental finding in specimens procured for a variety of reasons. In the vagina, the lesions usually presented themselves as polyps or cysts, although occasionally they were an incidental finding. The 2 vulval cases were incidental findings in punch biopsies. The basic morphological features were of epithelial elements of both glandular and squamous type; in some cases, the glandular elements formed a double cell layer. Uncommon findings included the presence of sebaceous glands in 2 cases (1 cervix, 1 vagina), basaloid formations resembling hair follicle structures in 4 (2 cervix, 2 vagina), and a microglandular proliferation resembling nephrogenic adenoma in 1 vaginal case. Prostate-specific antigen was positive in 13 of 26 cases and prostatic acid phosphatase in 16 of 26 tested. Six cases were negative with both markers. We propose that these benign lesions in the cervix, vagina, and vulva are derived from eutopic or misplaced Skene's glands. PMID- 21979600 TI - Ovarian low-grade serous carcinoma involving the cervix mimicking a cervical primary. AB - We describe the clinicopathologic and immunohistochemical features of the first reported case of an ovarian low-grade serous carcinoma metastatic to the cervix mimicking a cervical primary. The patient, a 55-year-old woman, was found to have an abnormal cervix and an abnormal Pap smear during a preoperative workup for a rectocele repair. A subsequent cervical biopsy contained moderately differentiated adenocarcinoma and the patient underwent a cold knife conization. An infiltrating adenocarcinoma was found in the anterior cervical lip, the neoplasm reached the surface of the endocervical canal and was composed of mildly to moderately atypical, eosinophilic or amphophilic columnar cells arranged in glands and papillae. Mitotic figures were rare and no apoptotic bodies were seen. Psammoma bodies and intraglandular mucinous material were also noted. There was extensive vascular/lymphatic invasion. The tumor extended to all margins and was interpreted as a moderately differentiated (grade 2) adenocarcinoma of the uterine cervix with a linear spread of at least 1.4 cm and a depth of at least 0.6 cm (FIGO stage 1B1). The patient was treated with radiotherapy and cisplatin. Six months later, surveillance imaging studies showed that the patient's ovaries seemed to be enlarging. The patient underwent exploratory laparotomy, bilateral salpingo-oophorectomy, right pelvic lymph node sampling, omentectomy, peritoneal biopsies, and pelvic washings. The ovaries contained bilateral cystic tumors. There was gross tumor involving multiple peritoneal sites. Microscopic examination of the ovaries showed the typical features of low-grade serous carcinoma associated with a serous neoplasm of low malignant potential with a cribriform pattern. Metastatic low-grade serous carcinoma was detected in multiple peritoneal sites and in the pelvic washings. A consultation was obtained, with the consultant concurring that the tumors represented independent primaries. The patient received carboplatin and taxol. Two and 4 years after the initial diagnosis, she experienced recurrences and was treated with carboplatin and taxol each time. After the second recurrence, the patient decided to seek additional advice about treatment options. The latter prompted a re-review of her histologic material. Upon this re-review, it was noted that the tumor in the cervix had some rather unusual features for a primary cervical adenocarcinoma, such as the lack of conspicuous mitotic activity, extensive vascular/lymphatic invasion in the context of a tumor with no solid areas, and only mild-to-moderate cytologic atypia. In addition, the tumor in the cervix had areas that were similar to the metastatic tumor present in the omentum. Immunoperoxidase staining for WT-1, estrogen receptor, and p16 was performed on the tumor in the cervix and on the ovarian tumor. The neoplastic cells in both tumors stained in a similar manner; the tumor cells were diffusely positive for WT-1 and estrogen receptor (90%) and focally positive for p16. No detectable signal for high-risk human papillomavirus was seen in the in-situ hybridization performed on the section of the tumor in the cervix. In summary, the histologic and immunohistochemical features and the in-situ hybridization results were in keeping with a diagnosis of metastatic ovarian low-grade serous carcinoma involving the cervix. This case underscores the importance of attentive histopathologic examination and the use of ancillary tests to ensure the recognition of the site of origin of a neoplasm involving the cervix. PMID- 21979601 TI - Proximal femur fracture in a patient referred to a physical therapist for knee pain. PMID- 21979602 TI - Longitudinal evaluation of balance quality using a modified bathroom scale: usability and acceptability. AB - We adapted a commercial bathroom scale in order to acquire the raw data from the weight sensors and then to send them to a server via a mobile phone. We investigated the usability and acceptability of the device in a long-term experiment with 22 elderly users that produced more than 5000 weight recordings. Four basic variables were extracted from the vertical force measurements and the stabilogram. The technology was accepted unreservedly, presumably because it did not differ from devices usually encountered in the home. The quantitative results showed a high variability of day-to-day measurement, which was countered by taking a moving average. A balance index was able to identify changes in balance over time. The preliminary results appear promising. PMID- 21979603 TI - Home-based telemanagement in chronic heart failure: an 8-year single-site experience. AB - During an eight-year period, 358 patients with chronic heart failure (CHF) were enrolled in a six-month home-based telemanagement (HBT) programme. The efficacy of the programme was evaluated in two four-year periods, based on changes in clinical, functional, Quality of Life (QoL) status and rate of hospital readmission. The New York Heart Association (NYHA) class and the number of patients with comorbidities increased significantly in the second period, while the number of patients with beta-blockers decreased significantly (P < 0.01). Following the HBT programme, non-cardiovascular hospital readmission rate and all cause readmission rate increased by 11% (P < 0.03) and 13% (P < 0.05), respectively. On re-evaluation after six months (238 patients) there was a general improvement in clinical, functional and QoL status and a significant increase in the mean daily dosage of beta-blockers prescribed. Our experience confirms that HBT for patients with CHF is associated with favourable effects on hospital readmission for cardiovascular reasons and on QoL. However, a more comprehensive multidisciplinary approach will probably be required to obtain favourable effects on total morbidity. PMID- 21979746 TI - Modelling peptide nanotubes for artificial ion channels. AB - We investigate the van der Waals interaction of D,L-Ala cyclopeptide nanotubes and various ions, ion-water clusters and C(60) fullerenes, using the Lennard Jones potential and a continuum approach which assumes that the atoms are smeared over the peptide nanotube providing an average atomic density. Our results predict that Li(+), Na(+), Rb(+) and Cl(-) ions and ion-water clusters are accepted into peptide nanotubes of 8.5 A internal diameter whereas the C(60) molecule is rejected. The model indicates that the C(60) molecule is accepted into peptide nanotubes of 13 A internal diameter, suggesting that the interaction energy depends on the size of the molecule and the internal diameter of the peptide nanotube. This result may be useful for the design of peptide nanotubes for drug delivery applications. Further, we also find that the ions prefer a position inside the peptide ring where the energy is minimum. In contrast, Li(+) water clusters prefer to be in the space between each peptide ring. PMID- 21979745 TI - Subchronic pulmonary pathology, iron overload, and transcriptional activity after Libby amphibole exposure in rat models of cardiovascular disease. AB - BACKGROUND: Surface-available iron (Fe) is proposed to contribute to asbestos induced toxicity through the production of reactive oxygen species. OBJECTIVE: Our goal was to evaluate the hypothesis that rat models of cardiovascular disease with coexistent Fe overload would be increasingly sensitive to Libby amphibole (LA)-induced subchronic lung injury. METHODS: Male healthy Wistar Kyoto (WKY), spontaneously hypertensive (SH), and SH heart failure (SHHF) rats were intratracheally instilled with 0.0, 0.25, or 1.0 mg LA (with saline as the vehicle). We examined bronchoalveolar lavage fluid (BALF) and histological lung sections after 1 week, 1 month, or 3 months for pulmonary biomarkers and pathology. SHHF rats were also assessed at 6 months for pathological changes. RESULTS: All animals developed concentration- and time-dependent interstitial fibrosis. Time-dependent Fe accumulation occurred in LA-laden macrophages in all strains but was exacerbated in SHHF rats. LA-exposed SHHF rats developed atypical hyperplastic lesions of bronchiolar epithelial cell origin at 3 and 6 months. Strain-related baseline differences existed in gene expression at 3 months, with persistent LA effects in WKY but not SH or SHHF rats. LA exposure altered genes for a number of pathways, including inflammation, immune regulation, and cell cycle control. Cell-cycle control genes were inhibited after LA exposure in SH and SHHF but not WKY rats, whereas tumor suppressor genes were induced only in WKY rats. The inflammatory gene expression also was apparent only in WKY rats. CONCLUSION: These data show that in Fe-overload conditions, progressive Fe accumulation occurs in fiber-laden macrophages within LA-induced lesions. Fe overload does not appear to contribute to chronic inflammation, and its role in hyperplastic lesion development requires further examination. PMID- 21979747 TI - Breast tenderness after initiation of conjugated equine estrogens and mammographic density change. AB - We examined the association between new-onset breast tenderness and change in mammographic density after initiation of conjugated equine estrogens (CEE). We analyzed baseline, year 1 and 2 data from 695 participants of the Women's Health Initiative Estrogen + Progestin (daily CEE 0.625 mg + medroxyprogesterone acetate 2.5 mg [MPA] or placebo) and Estrogen-Alone (CEE 0.625 mg or placebo) trials who participated in the Mammogram Density Ancillary Study. Using multivariable repeated measures models, we analyzed the association between new-onset breast tenderness (i.e. absence of baseline tenderness and presence of tenderness at year 1 follow-up) and change from baseline in percent mammographic density. Active therapy increased the odds of new-onset breast tenderness (CEE + MPA vs. placebo risk ratio [RR] 3.01, 95% confidence interval [95% CI] 1.96-4.62; CEE vs. placebo RR 1.70, 95% CI 1.14-2.53). Among women assigned to CEE + MPA, mean increase in mammographic density was greater among participants reporting new onset of breast tenderness than among participants without new-onset breast tenderness (11.3 vs. 3.9% at year 1, 9.4 vs. 3.2% at year 2, P < 0.001). Among women assigned to CEE alone, increase in mammographic density at year 1 follow-up was not significantly different in women with new-onset breast tenderness compared to women without new-onset breast tenderness (2.4 vs. 0.6% at year 1, 2.2 vs. 1.0% at year 2, P = 0.30). The new-onset of breast tenderness after initiation of CEE + MPA, but not CEE alone, is associated with greater increases in mammographic density. PMID- 21979748 TI - Artemin as an efficient molecular chaperone. AB - Artemin is an abundant thermostable protein in Artemia encysted embryos under stress. It is considered as a stress protein, as its highly regulated expression is associated with stress resistance in this crustacea. In the present study, artemin has been shown to be a potent molecular chaperone with high efficacy. Artemin is capable of inhibiting the chemical aggregation of proteins such as carbonic anhydrase (CA) and horseradish peroxidase (HRP) at unique molar ratios of chaperone to substrates (1:40 and 1:26 for CA and HRP, respectively). Furthermore, it can also enhance refolding yield of these substrates by nearly 50%. The refolding promotion of CA is checked and verified through a sensitive fluorimetric technique. Based on these experiments, artemin showed higher chaperone activity than other chaperones. The evaluation of artemin surface using ANS showed it to be highly hydrophobic, probably resulting in its high efficacy. These results suggest that artemin can be considered a novel low molecular weight chaperone. PMID- 21979749 TI - Long-term outcome of pleurodesis with OK-432 in metastatic breast cancer: a new risk model for success from an analysis of 75 cases. AB - BACKGROUND: Malignant pleural effusion is a common and devastating complication of metastatic breast cancer. This occurs in about 30% of patients with metastatic breast cancer during the clinical course, and chemical pleurodesis is sometimes performed to relieve dyspnea. However, the long-term outcome of pleurodesis and factors affecting successful pleurodesis have not been clarified. OBJECTIVES: The aim of this analysis is to evaluate the long-term outcome of pleurodesis and to identify risk factors associated with success. METHODS: Data on 75 patients who had undergone chemical pleurodesis with OK-432 for pleural effusion due to metastatic breast cancer were reviewed retrospectively. The primary outcomes were success rate and pleural progression-free survival (PPFS) rate. RESULTS: The median duration of follow-up was 134 days (range 8-975 days). During this period, 22 patients re-accumulated pleural fluid. The overall success rate was 70.5%. The 4-, 8- and 12-week PPFS rates were 88.0, 84.0 and 78.7% respectively. Multivariate analysis identified three unfavorable factors that were independently associated with unsuccessful pleurodesis, including estrogen receptor negative status, a 24-h drainage volume of more than 100 mL before extubation and NSAID use. The PPFS rate at median follow-up was 93.5% in the low risk group (n = 41, 0 or 1 unfavorable factor) and 55.1% in the high-risk group (n = 34, 2 or 3 unfavorable factors). The difference between the PPFS curves of the two risk groups was statistically significant (P < 0.001). CONCLUSIONS: Pleurodesis for metastatic breast cancer was efficacious in controlling malignant pleural effusion. Our simple new risk model warrants further studies. PMID- 21979750 TI - Sperm banking and assisted reproductive outcome in men with cancer: a 10 years' experience. AB - BACKGROUND: As cancer therapy can be harmful to spermatogenesis, men are generally advised to cryopreserve sperm before gonadotoxic treatment. Here, we compared fresh and frozen-thawed sperm quality in patients according to cancer type, and reported use rate in subsequent assisted reproductive technology (ART) cycles. METHODS: This retrospective analysis of a sperm cryopreservation program in all men suffering from cancer was conducted at the University Hospital of Nantes between 1997 and 2007. RESULTS: A total of 1042 men were referred for sperm cryopreservation during this period (438 testicular cancer, 184 other solid cancers, 278 lymphoma and 142 other haematological malignancies). A total of 2577 ejaculates from 1009 men were studied. Sperm characteristics and sperm sensitivity to the freezing process varied according to the cancer type. Frozen sperm was used in 82 patients, with 112 in vitro fertilization and 66 intrauterine insemination cycles performed, leading to a clinical pregnancy rate per cycle of 23.2 and 12%, respectively. CONCLUSION: Sperm quality and motility alteration during the freezing process can differ according to the type of cancer, but sperm frozen before gonadotoxic treatment in cancer patients can be successfully used in ART. PMID- 21979751 TI - Base promoted synthesis of activated cyclopropanes bearing homologated carbonyl groups via tandem Michael addition-intramolecular enolate trapping. AB - A simple base promoted intramolecular Michael initiated ring closure reaction of gamma-hydroxyenone derived diphenyl phosphinates with 1,3-indandione, enabled the synthesis of novel activated cyclopropanes with homologated carbonyl moiety in good yield. Promising levels of enantioselectivity are achieved when using cinchona derivatives as promoters. PMID- 21979752 TI - p38 mitogen-activated protein kinase and liver X receptor-alpha mediate the leptin effect on sterol regulatory element binding protein-1c expression in hepatic stellate cells. AB - Leptin, a key hormone in regulating energy homeostasis, is mainly produced by adipocytes. Cogent evidence indicates a unique role of leptin in the promotion of liver fibrosis. Hepatic stellate cell (HSC) activation is a pivotal step in the process of liver fibrosis. Sterol regulatory element binding protein (SREBP)-1c, a critical transcription factor for lipid synthesis and adipocyte differentiation, functions as a key transcription factor in inhibition of HSC activation. SREBP-1c is highly expressed in quiescent HSCs and downregulated upon HSC activation. The aim of this study is to examine the effect of leptin on SREBP 1c gene expression in HSCs in vitro and in vivo and elucidate the underlying mechanisms. The results of the present study demonstrated that leptin strongly inhibited SREBP-1c expression in HSCs in vivo and in vitro. p38 MAPK was involved in leptin regulation of SREBP-1c expression in cultured HSCs. Leptin-induced activation of p38 MAPK led to the decreases in liver X receptor (LXR)-alpha protein level, activity and its binding to the SREBP-1c promoter, which caused the downregulation of SREBP-1c expression. Moreover, leptin inhibition of SREBP 1c expression via p38 MAPK increased the expression of alpha1(I) collagen in HSCs. Our results might provide new insights into the mechanisms of the unique role of leptin in the development of liver fibrosis and might have potential implications for clarifying the molecular mechanisms underlying liver fibrosis in diseases in which circulating leptin levels are elevated such as nonalcoholic steatohepatitis, type 2 diabetes mellitus and alcoholic cirrhosis. PMID- 21979754 TI - Traumatic mitral valve rupture. PMID- 21979753 TI - Sorafenib-induced apoptosis of chronic lymphocytic leukemia cells is associated with downregulation of RAF and myeloid cell leukemia sequence 1 (Mcl-1). AB - We have previously shown that sorafenib, a multikinase inhibitor, exhibits cytotoxic effects on chronic lymphocytic leukemia (CLL) cells. Because the cellular microenvironment can protect CLL cells from drug-induced apoptosis, it is important to evaluate the effect of novel drugs in this context. Here we characterized the in vitro cytotoxic effects of sorafenib on CLL cells and the underlying mechanism in the presence of marrow stromal cells (MSCs) and nurselike cells (NLCs). One single dose of 10 MUmol/L or the repeated addition of 1 MUmol/L sorafenib caused caspase-dependent apoptosis and reduced levels of phosphorylated B-RAF, C-RAF, extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription 3 (STAT3) and myeloid cell leukemia sequence 1 (Mcl-1) in CLL cells in the presence of the microenvironment. We show that the RAF/mitogen-activated protein kinase kinase (MEK)/ERK pathway can modulate Mcl-1 expression and contribute to CLL cell viability, thereby associating so-rafenib cytotoxicity to its impact on RAF and Mcl-1. To evaluate if the other targets of sorafenib can affect CLL cell viability and contribute to sorafenib-mediated cytotoxicity, we tested the sensitivity of CLL cells to several kinase inhibitors specific for these targets. Our data show that RAF and vascular endothelial growth factor receptor (VEGFR) but not KIT, platelet-derived growth factor receptor (PDGFR) and FMS-like tyrosine kinase 3 (FLT3) are critical for CLL cell viability. Taken together, our data suggest that sorafenib exerts its cytotoxic effect likely via inhibition of the VEGFR and RAF/MEK/ERK pathways, both of which can modulate Mcl-1 expression in CLL cells. Furthermore, sorafenib induced apoptosis of CLL cells from fludarabine refractory patients in the presence of NLCs or MSCs. Our results warrant further clinical exploration of sorafenib in CLL. PMID- 21979755 TI - Clinical worsening after pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension. AB - INTRODUCTION: Pulmonary endarterectomy (PEA) is the most effective treatment for chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study is to evaluate long-term survival and freedom from clinical worsening after PEA. METHODS: All patients who underwent PEA in our hospital between May 2000 and August 2009 were included. Follow-up parameters were all-cause mortality and time to clinical worsening, defined as a combination of death, need for pulmonary hypertension-specific medication or 15% decrease in six-minute walk distance without improvement in functional class. The Cox proportional hazard regression was used to identify predictors. RESULTS: Seventy-four consecutive patients (mean age 55.9 +/- 13.8 years, 51% female) underwent PEA. Prior to surgery, 55 patients were in NYHA functional class III or higher. The mean pulmonary artery pressure was 41.3 +/- 11.9 mmHg with a mean pulmonary vascular resistance of 521 +/- 264 dyn.s.cm(-5) (range 279-1331 dyn.s.cm(-5)). Five patients (6.8%) died in hospital. Out of hospital, 5 out of 69 patients (7.2%) died during a median follow-up of 3.7 +/- 2.2 years [range 0.1-8.5 years]). The one- and five-year survival rates were 93% and 89%, respectively. During follow-up, clinical worsening occurred in 13 out of 69 patients (18.8%). The one- and five-year rates of freedom from clinical worsening were 94% and 72%, respectively. The baseline NT-pro BNP level tended to be a predictor for occurrence of clinical worsening. CONCLUSION: Pulmonary endarterectomy is associated with good long-term survival in patients with CTEPH. However, clinical worsening occurred in a substantial number of patients at long-term follow-up. PMID- 21979758 TI - Altered calcium signaling in colonic smooth muscle of type 1 diabetic mice. AB - Seventy-six percent of diabetic patients develop gastrointestinal symptoms, such as constipation. However, the direct effects of diabetes on intestinal smooth muscle are poorly described. This study aimed to identify the role played by smooth muscle in mediating diabetes-induced colonic dysmotility. To induce type 1 diabetes, mice were injected intraperitoneally with low-dose streptozotocin once a day for 5 days. Animals developed hyperglycemia (>200 mg/dl) 1 wk after the last injection and were euthanized 7-8 wk after the last treatment. Computed tomography demonstrated decreased overall gastrointestinal motility in the diabetic mice. In vitro contractility of colonic smooth muscle rings from diabetic mice was also decreased. Fura-2 ratiometric Ca(2+) imaging showed attenuated Ca(2+) increases in response to KCl stimulation that were associated with decreased light chain phosphorylation in diabetic mice. The diabetic mice also exhibited elevated basal Ca(2+) levels, increased myosin phosphatase targeting subunit 1 expression, and significant changes in expression of Ca(2+) handling proteins, as determined by quantitative RT-PCR and Western blotting. Mice that were hyperglycemic for <1 wk also showed decreased colonic contractile responses that were associated with decreased Ca(2+) increases in response to KCl stimulation, although without an elevation in basal Ca(2+) levels or a significant change in the expression of Ca(2+) signaling molecules. These data demonstrate that type 1 diabetes is associated with decreased depolarization induced Ca(2+) influx in colonic smooth muscle that leads to attenuated myosin light chain phosphorylation and impaired colonic contractility. PMID- 21979759 TI - Update in medical education 2010-2011. PMID- 21979757 TI - Suppression of the HPA axis during extrahepatic biliary obstruction induces cholangiocyte proliferation in the rat. AB - Cholestatic patients often present with clinical features suggestive of adrenal insufficiency. In the bile duct-ligated (BDL) model of cholestasis, the hypothalamic-pituitary-adrenal (HPA) axis is suppressed. The consequences of this suppression on cholangiocyte proliferation are unknown. We evaluated 1) HPA axis activity in various rat models of cholestasis and 2) effects of HPA axis modulation on cholangiocyte proliferation. Expression of regulatory molecules of the HPA axis was determined after BDL, partial BDL, and alpha naphthylisothiocyanate (ANIT) intoxication. The HPA axis was suppressed by inhibition of hypothalamic corticotropin-releasing hormone (CRH) expression by central administration of CRH-specific Vivo-morpholinos or by adrenalectomy. After BDL, the HPA axis was reactivated by 1) central administration of CRH, 2) systemic ACTH treatment, or 3) treatment with cortisol or corticosterone for 7 days postsurgery. There was decreased expression of 1) hypothalamic CRH, 2) pituitary ACTH, and 3) key glucocorticoid synthesis enzymes in the adrenal glands. Serum corticosterone and cortisol remained low after BDL (but not partial BDL) compared with sham surgery and after 2 wk of ANIT feeding. Experimental suppression of the HPA axis increased cholangiocyte proliferation, shown by increased cytokeratin-19- and proliferating cell nuclear antigen-positive cholangiocytes. Conversely, restoration of HPA axis activity inhibited BDL induced cholangiocyte proliferation. Suppression of the HPA axis is an early event following BDL and induces cholangiocyte proliferation. Knowledge of the role of the HPA axis during cholestasis may lead to development of innovative treatment paradigms for chronic liver disease. PMID- 21979760 TI - Helping our patients to adhere to chronic medications: a new arrow for the quiver. PMID- 21979761 TI - Using new evidence is an innovation. So what? PMID- 21979762 TI - In deep cavities stepwise excavation of caries can preserve the pulp. AB - DATA SOURCES: Medline and the Igaku Chuo Zasshi (Japanese) databases, the reference list of identified studies and personal reprint collections of authors were searched. STUDY SELECTION: Randomised controlled trials (RCT), controlled clinical trials (CCT) and case series conducted in permanent teeth were included. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted the data using specially designed forms. A qualitative synthesis is presented. RESULTS: Ten English and three Japanese studies were finally included (two RCTs, five CCTs and six case series). CONCLUSIONS: From this review, stepwise excavation can be concluded as effective for pulp preservation in extremely deep caries where there are no clinical symptoms of irreversible pulpitis. Calcium hydroxide and other materials, such as antimicrobials and polycarboxylate cement combined with tannin fluoride preparation, have been shown to be effective in reducing bacteria after stepwise excavation. Further clinical trials with high levels of study design in this research field are needed to identify the best possible methods for removing carious dentine during stepwise excavation. PMID- 21979763 TI - The safety of oscillating-rotating powered toothbrushes. AB - DATA SOURCES: PubMed-Medline, the Cochrane Central Register of Controlled Trials (Cochrane-CENTRAL), Embase, together with the reference lists of selected studies were searched. STUDY SELECTION: Both in vitro and in vivo studies were included with selection being undertaken by two reviewers with a third as arbiter if required. Human randomised clinical trials (RCT) or controlled clinical trials conducted in healthy subjects were included where, the intervention included a rechargeable, oscillating-rotating power toothbrush compared with a manual toothbrush control and a safety assessment was included. Similar criteria were used for in vitro studies. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted the data with any discrepancies being decided by a third reviewer. Missing data were calculated and designated accordingly. Meta-analysis was performed where possible using a random-effects model. RESULTS: Thirty-five publications met the criteria. The mean change in gingival recession was not significantly different among toothbrush groups in the two selected trials with safety as a primary outcome (weighted mean difference: 0.03). A meta-analysis of the five trials that evaluated safety with a surrogate parameter was not possible; however, there were no significant between-group differences at the study end in any trial. A descriptive analysis of the 24 selected studies assessing safety as a secondary outcome revealed few brushing-related adverse events. The heterogeneity in objectives and methodology of the four in vitro trials that met the eligibility criteria precluded generalisation of the results. CONCLUSIONS: A large body of published research in the preceding two decades has consistently shown oscillating-rotating toothbrushes to be safe compared to manual toothbrushes, demonstrating that these power toothbrushes do not pose a clinically relevant concern to hard or soft tissues. PMID- 21979764 TI - Prevention of root caries. AB - DESIGN: Randomised controlled trial. INTERVENTION: Elders having at least five teeth with exposed roots, no serious medical problems and basic self-care ability (including oral hygiene practices) were randomly allocated into one of four prevention groups. Individualised oral hygiene instruction was provided to each participant, focusing on effective brushing with a manual toothbrush, and use of fluoride toothpaste was recommended. Before applications of the study agents, a piece of gauze was used to clean and dry the teeth. Then water (placebo control), chlorhexidine varnish (Cervitec, Ivoclar Vivadent AG, Schaan, Liechtenstein), sodium fluoride varnish (Duraphat, Pharbil Waltrop GmbH, Waltrop, Germany) or SDF solution (Saforide, Toyo Seiyaku Kasei Co. Ltd., Osaka, Japan) was applied onto the exposed root surfaces of participants in the respective groups by means of a disposable microbrush. The participants were instructed not to eat for half an hour after treatment. Applications of water or SDF solution were repeated every 12 months, and applications of chlorhexidine varnish or sodium fluoride varnish were repeated every three months. OUTCOME MEASURES: Root Caries Index (RCI) was calculated as follows: (no. of root caries lesions/no. of teeth with gingival recession/person) * 100. Treatment effects were also measured by prevented fraction (PF), relative risk and the number (of elders) needed to treat (NNT) to prevent one elder from developing root caries. RESULTS: Two thirds (203/306) of the included elders were followed for three years. Significantly lower relative risks for developing new root caries were found in the elders in the chlorhexidine, sodium fluoride and SDF groups compared with the control (OHI only) group. The mean numbers of new root caries surfaces in the four groups were 2.5, 1.1, 0.9 and 0.7 respectively (ANOVA, p < 0.001). The prevented fraction and numbers needed to treat are shown in Table 1. CONCLUSIONS: Applications of SDF solution, sodium fluoride varnish and chlorhexidine varnish are more effective in preventing new root caries than OHI alone. The results of this study provide support for the clinical and community use of the three test materials, in addition to improvement in oral hygiene, to prevent the development of root caries in institutionalised elders. PMID- 21979765 TI - Root-filled teeth with adequate restorations and root canal treatment have better treatment outcomes. AB - DATA SOURCES: Medline, Embase, the Cochrane Library, the Wiley online database, four journals (Journal of Endodontics, International Endodontic Journal, Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology and Endodontics and Dental Traumatology) and the references of identified articles were searched manually. There was no language restriction. STUDY SELECTION: Clinical studies that provided sample size, and where success was based on radiographic and/or clinical criteria that evaluated quality of root filling, the quality of coronal restoration and periapical status at least one year after root canal treatment that provided an overall success rate or sufficient data to allow it to be calculated from the raw data were included. DATA EXTRACTION AND SYNTHESIS: Data were collected based on predetermined criteria. Percentages of teeth without apical periodontitis were recorded for each category: adequate root canal treatment (AE); inadequate root canal treatment (IE); adequate restoration (AR); and inadequate restoration (IR). Data were analysed using meta-analysis for odds ratios (ORs). RESULTS: Nine article were included . After adjusting for significant covariates to reduce heterogeneity, the results were combined to obtain pooled estimates of the common OR for the comparison of AR/AE versus AR/IE:-AR/AE versus AR/IE (OR = 2.734; 95%CI, 2.61-2.88; P < .001)AR/AE versus IR/AE (OR = 2.808; 95% CI, 2.64-2.97; P < .001). CONCLUSIONS: On the basis of the current best available evidence, the odds for healing of apical periodontitis increase with both adequate root canal treatment and adequate restorative treatment. Although poorer clinical outcomes may be expected with adequate root filling-inadequate coronal restoration and inadequate root filling-adequate coronal restoration, there is no significant difference in the odds of healing between these two combinations. PMID- 21979766 TI - Laser therapy for dentine hypersensitivity. AB - DATA SOURCES: Medline, Embase, the Cochrane Central database as well as the Cochrane Oral Health Group's Trials Register and the National Research Register. In addition relevant journals were hand searched from 2000 to 2010 (Lasers in Medical Sciences, Lasers in Surgery and Medicine, Photomedicine and Laser Surgery, Photodiagnosis and Photodynamic Therapy, Journal of Oral Rehabilitation, Journal of Periodontology, Journal of Clinical Periodontology, Journal of Endodontics, Clinical Oral Investigations, Journal of Dental Research, Journal of Oral Laser Applications, Journal of Periodontal Research and Periodontology 2000) together with the reference lists of relevant trials. STUDY SELECTION: Randomised controlled trials (RCT) that included patients with two or more hypersensitive teeth confirmed by evaporative stimulus or tactile hypersensitivity assessment, comparing laser therapy versus other topical desensitising agents, such as fluoride varnish, dentine bonding agents etc, that were published in English. DATA EXTRACTION AND SYNTHESIS: Studies were assessed for quality by two reviewers independently and data were extracted using a standardised form. Because of heterogeneity of the studies meta-analysis was not performed, so a qualitative synthesis is presented. RESULTS: Eight trials (234 participants) met the inclusion criteria. Half of the included studies compared GaALAS laser with topical desensitising agents, but the findings were conflicting. The remaining studies involved Nd:YAG laser, Er:YAG laser and CO2 laser, and all showed that the three types of lasers were superior to topical desensitising agents, but the superiority was slight. CONCLUSIONS: The review suggests that laser therapy has a slight clinical advantage over topical medicaments in the treatment of dentine hypersensitivity. However more large sample-sized, long-term, high-quality randomised controlled clinical trials are needed before definitive conclusions can be made. PMID- 21979767 TI - Alcohol consumption a risk factor for periodontal disease. AB - DATA SOURCES: Medline, LILACS, SciELO and Cochrane Central Register of Controlled Trials (CENTRAL). STUDY SELECTION: The papers were screened independently by two reviewers: disagreements were resolved by a third reviewer. Randomised-controlled trials (RCTs), controlled clinical trials (CCTs), cohort studies, case-control and cross-sectional studies in English were included. Quality was assessed using STROBE methodology (www.strobe-statement.org). DATA EXTRACTION AND SYNTHESIS: Quality was assessed using STROBE methodology (www.strobe-statement.org). Owing to heterogeneity among studies concerning the methods of assessment of alcohol dependence, alcohol consumption and periodontitis no meta-analysis was performed. RESULTS: Eleven cross-sectional and five longitudinal observational studies met the inclusion criteria. Seven of the 12 studies on alcohol consumption and all of the four studies on alcohol dependence reported positive associations between alcohol intake and periodontitis. Although smoking was properly addressed in all selected studies, the confounding effect of dental plaque was taken into account in only six studies. CONCLUSIONS: There is evidence to suggest alcohol consumption is a risk indicator for periodontitis. Longitudinal studies on the association of alcohol dependence and alcohol consumption with periodontitis are needed to confirm the association or not. PMID- 21979768 TI - Causal association between smoking and tooth loss is highly likely. AB - DATA SOURCES: Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and hand searching of the journals; Community Dentistry and Oral Epidemiology, Gerodontology, Journal of Clinical Periodontology, Journal of Dental Research, Journal of Periodontology, Journal of Periodontal Research, Journal of Public Health Dentistry and Oral Diseases. Any potential studies in the reference lists of the identified articles read completely were also considered. STUDY SELECTION: Studies published in English investigating associations between smoking and tooth loss and reporting the effect size were included. Literature reviews and studies that combined former smokers with non smokers or current smokers were excluded. DATA EXTRACTION AND SYNTHESIS: Data were extracted by one reviewer and verified independently by another with disagreements being resolved by discussion. Methodological quality of studies was assessed using the modified Newcastle-Ottawa Scale (NOS). A qualitative summary is presented. RESULTS: Six cross-sectional and two cohort studies were included examining 58,755 subjects in four countries. All studies reported significant associations, although the strength of the association was usually moderate. Four studies reported dose-response relationships between exposure to smoking and the risk of developing tooth loss. A decrease in the risk of tooth loss for former smokers was evident in six studies. Interpretation of evidence for each element was consistent, despite some shortcomings regarding study type and population. CONCLUSIONS: Based on the consistent evidence found with the existing biological plausibility, a causal association between smoking and tooth loss is highly likely. Further studies using a cohort design and different populations are necessary to confirm this association. PMID- 21979769 TI - Photodynamic therapy for chronic periodontitis. AB - DATA SOURCES: Medline, Embase, The Cochrane Oral Health Group's Trials Register, CENTRAL, UK National Research Register, ISI Proceedings, hand search of relevant journals for 2000-2008. References from selected articles and contact with authors. STUDY SELECTION: Randomised controlled trials in any language comparing scaling and root planing (SRP) alone and SRP with PDT in patients with chronic periodontitis, with a mean follow up of at least 12 weeks. The primary outcome measure was the change in clinical attachment loss (CAL). Secondary outcomes were changes in probing depth (PD) and gingival recession (GR). DATA EXTRACTION AND SYNTHESIS: Data were extracted by a single reviewer using a standard extraction form. Quality was assessed using both the Jadad scale and the allocation concealment component of the Cochrane risk of bias tool. Meta-analysis was conducted using the random effects model. Heterogeneity was assessed using the chi-squared-based Q statistic method and Higgins' I(2) test. RESULTS: Four trials with 101 participants were included. The risk of bias of these trials was considered to be moderate. The mean difference in CAL at 12 weeks was 0.29 mm (95% CI 0.08-0.50, p=0.007). Heterogeneity was high using both the Chi(2) and I(2) tests. CONCLUSIONS: The review suggests there may be a minor improvement in clinical attachment loss at 12 weeks. It is unclear whether this is a clinically meaningful improvement. PMID- 21979770 TI - Are lasers as effective as scaling for chronic periodontitis? AB - DATA SOURCES: Medline, Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE), CINAHL, Science Direct, ISI Web of Science, and SCOPUS. The following journals were hand searched: Journal of Periodontology, International Journal of Periodontics and Restorative Dentistry, Journal of Clinical Periodontology, Journal of Dental Research, Journal of Periodontal Research, Periodontology 2000, Journal of Dentistry, Journal of American Dental Associations, Journal of Clinical Dentistry, Lasers in Medical Science, Lasers in Surgery and Medicine, Clinical Oral Investigations, and Photomedicine and Laser Surgery as well as the reference lists of included articles. STUDY SELECTION: Randomised controlled clinical trials (RCTs) comparing Er:YAG laser with manual or ultrasonic SRP alone were included. No language restrictions were applied. DATA EXTRACTION AND SYNTHESIS: Data were collected by two independent reviewers with only numeric data being extracted. Data were combined for meta-analysis with the effect size being estimated and reported as the mean difference (MD) for continuous variables using a random effects model. Heterogeneity was assessed using the /2-based Q-statistic method and I(2) measurement. RESULTS: Five trials met the inclusion criteria. Five trials (85 patients and 3,564 sites) were entered in the meta-analysis to investigate clinical attachment level (CAL) gain, pocket depth (PD) reduction and gingival recession (GR). All studies reported significant intragroup improvement in clinical and microbiological parameters in patients treated with the Er:YAG laser. However, three studies did not report a significant difference between Er:YAG laser and SRP groups in CAL gain, PD reduction or GR changes. The meta analysis revealed no significant differences for any investigated parameters at six and 12 months. CONCLUSIONS: Significant heterogeneity, a high risk of bias in three of the five included studies, and methodological shortcomings indicate that the results should be considered with caution. Future long-term, well-designed RCTs are needed to assess the scientific evidence of Er:YAG laser efficacy as an alternative treatment strategy to SRP. PMID- 21979771 TI - Can dental implants osseointegrate in oral cancer patients? AB - DATA SOURCES: Medline from 1986 to September 2010. Hand-searching of unspecified journals over an unspecified period of time. STUDY SELECTION: Clinical studies, though not confined to a particular type (e.g. randomised controlled trial), involving patients having undergone radio- and chemotherapy following oral cancer surgery. Only those articles published in English were included. DATA EXTRACTION AND SYNTHESIS: No details are given of the number of reviewers, of any quality assessment of the included papers, nor of how they proposed to synthesise the data or conduct subgroup and sensitivity analysis. RESULTS: A narrative report of findings from 21 included studies. No report is made of the types of study, nor their quality. In 16 studies that examined whether dental implants osseointegrated following radiation, between 68% and 100% did (no confidence intervals reported). Studies ranged in duration from 2 months to 13 years. CONCLUSIONS: Dental implants can osseointegrate and remain functionally stable in patients having undergone oral cancer therapy. PMID- 21979772 TI - Bonded molar tubes associated with higher failure rate than molar bands. AB - DATA SOURCES: The Cochrane Oral Health Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, and Conference proceedings and abstracts from the British Orthodontic Conference, European Orthodontic Conference and the International Association of Dental Research were searched. STUDY SELECTION: Randomised controlled clinical trials (RCT) including those that use a split-mouth design were included. There were no restrictions regarding the language. DATA EXTRACTION AND SYNTHESIS: The selection of papers, decisions about eligibility and data extraction were carried out independently and in duplicate without blinding to the authors, adhesives used or results obtained. All disagreements were resolved by discussion. Comparisons were to be made firstly between any of the five main types of adhesive. If possible, comparisons were to be made within groups and, where appropriate, between chemical- and light-cured adhesives.Meta-analysis was to be undertaken only on studies of similar comparisons reporting the same outcome measures. RESULTS: Two trials (n = 190), at low risk of bias, were included in the review and both presented data on first time failure at the tooth level. Pooling of the data showed a statistically significant difference in favour of molar bands, with a hazard ratio of 2.92 (95% confidence intervals (CI) 1.80 to 4.72). No statistically significant heterogeneity was shown between the two studies. Data on first time failure at the patient level were also available and showed a statistically different difference in favour of molar bands (risk ratio 2.30; 95% CI 1.56 to 3.41) (risk of event for molar tubes = 57%; risk of event for molar bands 25%). One trial presented data on decalcification, again showing a statistically significant difference in favour of molar bands. No other adverse events were identified. CONCLUSIONS: From the two well-designed and low risk of bias trials included in this review it was shown that the failure of molar tubes bonded with either a chemically-cured or light-cured adhesive was considerably higher than that of molar bands cemented with glass ionomer cement. One trial indicated that there was less decalcification with molar bands cemented with glass ionomer cement than with bonded molar tubes cemented with a light-cured adhesive. However, given there are limited data for this outcome, further evidence is required to draw more robust conclusions. PMID- 21979773 TI - Insufficient evidence for effectiveness of any treatment for oral lichen planus. AB - DATA SOURCES: The Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), Medline and Embase databases were searched with no restrictions regarding language or date of publication. Bibliographies of identified publications were also checked for relevant studies, and authors were contacted to identify missing and unreported trials. The WHO International Trials Registry Platform was searched for ongoing studies, using the term 'oral lichen planus'. STUDY SELECTION: Randomised controlled clinical trials (RCTs) of therapy for symptomatic OLP which compared treatment with a placebo or between treatments or no intervention were considered for this review. DATA EXTRACTION AND SYNTHESIS: The titles and abstracts of all reports identified were scanned independently by two review authors. All studies meeting the inclusion criteria were assessed for risk of bias and data were extracted. For dichotomous outcomes, the estimates of effects for the intervention were expressed as risk ratios (RR) together with 95% confidence intervals. For continuous outcomes, mean differences (MD) and 95% confidence intervals were used to summarise the data. Meta-analyses were conducted for studies with similar comparisons reporting the same outcome measures. RESULTS: Twenty-eight trials were included. Although topical steroids are considered first line treatment for symptomatic OLP, we identified no RCTs that compared steroids with placebo. There is no evidence from the three trials of pimecrolimus that this treatment is better than placebo in reducing pain from OLP. There is weak evidence from two trials, at unclear and high risk of bias respectively, that aloe vera may be associated with a reduction in pain compared to placebo, but it was not possible to pool the pain data from these trials. There is weak and unreliable evidence from two small trials, at high risk of bias, that cyclosporin may reduce pain and clinical signs of OLP, but meta-analysis of these trials was not possible.There were five trials that compared steroids with calcineurin inhibitors, each evaluating a different pair of interventions. There is no evidence from these trials that there is a difference between treatment with steroids compared to calcineurin inhibitors with regard to reducing pain associated with OLP. From six trials there is no evidence that any specific steroid therapy is more or less effective at reducing pain compared to another type or dose of steroid. CONCLUSIONS: From the 28 trials included in this systematic review, the wide range of interventions compared means there is insufficient evidence to support the effectiveness of any specific treatment as being superior. PMID- 21979774 TI - Socio-economic status and upper aerodigestive tract cancer. AB - DESIGN: A multicentre case-control study. CASE/CONTROL SELECTION: Cases were defined as those diagnosed with primary squamous cell tumours of the UADT between 2002 and 2005. Diagnoses included malignant cancers of the oral cavity, oropharynx, hypo-pharynx, larynx or oesophagus. Incident cases were ascertained through weekly monitoring of head and neck cancer clinics in hospital departments and confirmed by pathology department records. Controls were frequency-matched to cases by sex and age (five-year groups). In the UK centres, population controls were randomly selected from the same community medical practice list as the corresponding cases. Specifically, for each case, a total of 10 controls were selected, matched by age and sex. Potential controls were approached in a random order one at a time until one agreed to participate. In all other centres, hospital controls were used. Only controls with a recently diagnosed disease were accepted, and admission diagnoses related to alcohol, tobacco or diet were excluded. Eligible diagnoses included endocrine and metabolic; genito-urinary; skin, subcutaneous tissue and musculoskeletal; gastro-intestinal; circulatory; ear, eye and mastoid; nervous system diseases; trauma and plastic surgery. The proportion of controls within a specific diagnostic group could not exceed 33% of the total in any particular centre. DATA ANALYSIS: Personal interviews collected information on demographics, lifetime occupation, history, smoking, alcohol consumption and diet. Socioeconomic status was measured by education, occupational social class and unemployment. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using unconditional logistic regression. RESULTS: When controlling for age, sex and centre, significantly increased risks for UADT cancer were observed for those with low versus high educational attainment OR = 1.98 (95% CI 1.67, 2.36). Similarly, for occupational socioeconomic indicators- comparing the lowest versus highest International Socio-Economic Index (ISEI) quartile for the longest occupation gave OR = 1.60 (1.28, 2.00); and for unemployment OR = 1.64 (1.24, 2.17). Statistical significance remained for low education when adjusting for smoking, alcohol and diet behaviours OR = 1.29 (1.06, 1.57) in the multivariate analysis. Inequalities were observed only among men but not among women and were greater among those in the British Isles and Eastern European countries than in Southern and Central/Northern European countries. Associations were broadly consistent for subsite and source of controls (hospital and community) CONCLUSIONS: Socioeconomic inequalities for UADT cancers are only observed among men and are not totally explained by smoking, alcohol drinking and diet. PMID- 21979775 TI - Limited evidence that acupuncture is effective for treating temporomandibular disorders. AB - DATA SOURCES: Medline, PubMed, The Cochrane Library 2010, CINAHL, Embase, seven Korean Medical Databases and a Chinese Medical Database (China Academic Journal, www.cnki.co.kr). STUDY SELECTION: Parallel or cross-over RCTs that assessed the efficacy of acupuncture regardless of blinding, language and type of reporting published in English, Chinese and Korean were included. Dissertations and abstracts were included provided they contained sufficient detail. Complex interventions in which acupuncture was not a sole treatment and studies with no reported clinical data were excluded. DATA EXTRACTION AND SYNTHESIS: All RCTs were obtained and read in full by two independent reviewers and data extracted according to pre-defined criteria. Quality was assessed using the Cochrane risk of bias criteria. Meta-analysis was conducted using random effect models if excessive statistical heterogeneity did not exist. Additional subgroup analysis or sensitivity analysis additionally was conducted to explore heterogeneity. Publication bias was assessed by funnel plot using the Cochrane software. RESULTS: Seven RCTs (including 141 patients) met our inclusion criteria. Six studies comparatively tested needle acupuncture against penetrating sham acupuncture, non-penetrating sham acupuncture or sham laser acupuncture, whilst the remaining study tested laser acupuncture against sham laser acupuncture. Five studies were considered to be at low risk of bias. Outcomes were reported for pain intensity, facial pain, muscle tenderness and mouth opening. CONCLUSIONS: This systematic review produced limited evidence that acupuncture is more effective than sham acupuncture in alleviating pain and masseter muscle tenderness in TMD. Further rigorous studies are, however, required to establish beyond doubt whether acupuncture has therapeutic value for this indication. PMID- 21979776 TI - Arthroscopy for treating temporomandibular joint disorders. AB - DATA SOURCES: The Cochrane Oral Health Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline Embase, Lilacs, Allied and Complementary Medicine Database (AMED) and CINAHL databases were searched. In addition the reference lists of the included articles were checked and 14 journals hand searched. STUDY SELECTION: Randomised controlled clinical trials (RCT) of arthroscopy for treating TMDs were included. There were no restrictions regarding the language or date of publication. DATA EXTRACTION AND SYNTHESIS: Two review authors independently extracted data, and three review authors independently assessed the risk of bias of included trials. The authors of the selected articles were contacted for additional information. Pooling of trials was only attempted if at least two trials of comparable protocols, with the same conditions and similar outcome measurements were available. Statistical analysis was performed in accordance with the Cochrane Collaboration guidelines. RESULTS: Seven RCTs (n = 349) met the inclusion criteria. All the studies were either at high or unclear risk of bias. Pain was evaluated after six months in two studies. No statistically significant differences were found between the arthroscopy versus nonsurgical groups (standardised mean difference (SMD) = 0.004; 95% confidence interval (CI) - 0.46 to 0.55, P = 0.81). Two studies analysed pain 12 months after surgery (arthroscopy and arthrocentesis) in 81 patients. No statistically significant differences were found (mean difference (MD) = 0.10; 95% CI -1.46 to 1.66, P = 0.90). Three studies analysed the same outcome in patients who had been submitted to arthroscopic surgery or to open surgery and a statistically significant difference was found after 12 months (SMD = 0.45; 95% CI 0.01 to 0.89, P = 0.05) in favour of open surgery.The two studies compared the maximum interincisal opening in six different clinical outcomes (interincisal opening over 35 mm; maximum protrusion over 5 mm; click; crepitation; tenderness on palpation in the TMJ and the jaw muscles 12 months after arthroscopy and open surgery). The outcome measures did not present statistically significant differences (odds ratio (OR) = 1.00; 95% CI 0.45 to 2.21, P = 1.00). Two studies compared the maximum interincisal opening after 12 months of postsurgical follow up. A statistically significant difference in favour of the arthroscopy group was observed (MD = 5.28; 95% CI 3.46 to 7.10, P < 0.0001).The two studies compared the mandibular function after 12 months of follow-up with 40 patients evaluated. The outcome measure was mandibular functionality (MFIQ). This difference was not statistically significant (MD = 1.58; 95% CI -0.78 to 3.94, P = 0.19). CONCLUSIONS: Both arthroscopy and nonsurgical treatments reduced pain after six months. When compared with arthroscopy, open surgery was more effective at reducing pain after 12 months. Nevertheless, there were no differences in mandibular functionality or in other outcomes in clinical evaluations. Arthroscopy led to greater improvement in maximum interincisal opening after 12 months than arthrocentesis; however, there was no difference in pain. PMID- 21979777 TI - Journal clubs most effective if tailored to learner needs. AB - DATA SOURCES: The search strategy was developed using Medline and adapted for the requirements of other databases. The strategy included all study types, enabling the retrieval of qualitative research. Databases searched were; Australian Education Index, ACP Journal Club, British Education Index, Cochrane Library, CINAHL, Embase, Eric, LISA Medline, metaRegister of Controlled Trials, National Research Register, Psychinfo, REFER, Sociological Abstracts, Web of Knowledge. Bibliographies of relevant publications and review articles were scanned and relevant references were retrieved. No language restrictions were applied. Information on databases searched provided by original authors as not included in published article. STUDY SELECTION: All study designs which evaluated whether clubs promote changes in learner reaction, attitudes, knowledge, skills, behaviour or patient outcomes in undergraduate, postgraduate and practice settings. Studies evaluating video/internet meetings or single meetings were excluded. DATA EXTRACTION AND SYNTHESIS: Each article was reviewed by two authors independently with pilot-tested data collection forms. No quality assessment was pre-specified. RESULTS: Eighteen studies were included. Studies reported improvements in reading behaviour (N=5/11), confidence in critical appraisal (N=7/7), critical appraisal test scores (N=5/7) and ability to use findings (N=5/7). No studies reported on patient outcomes. Sixteen studies used self reported measures, but only four studies used validated tests. Interventions were too heterogeneous to allow pooling. Realist synthesis identified potentially 'active educational ingredients', including mentoring, brief training in clinical epidemiology, structured critical appraisal tools, adult-learning principles, multifaceted teaching approaches and integration of the JC with other clinical and academic activities. CONCLUSIONS: The effectiveness of JCs in supporting evidence-based decision making is not clear. Better reporting of the intervention and a mixed methods approach to evaluating active ingredients are needed in order to understand how JCs may support evidence-based practice. PMID- 21979780 TI - [Evaluation of a New Protocol for Two-isotope (123)I-BMIPP/(99m)Tc-TF Single Photon Emission Computed Tomography (SPECT) to Detect Myocardial Damage within One Hour]. AB - Objective The present study aimed at establishing a new protocol using both (99m)Tc-Tetrofosmin (TF) and (123)I-BMIPP SPECT to detect myocardial damage within one hour. Methods Initial (123)I-BMIPP SPECT was immediately followed by (99m)Tc-TF SPECT. The influence of (123)I scattered rays on (99m)Tc energy windows set at 15% and 10% were measured using an RH-2 phantom. Participants in the study were patients with heart diseases who had provided written informed consent to undergo the new protocol. The patients maintained the MONZEN position throughout the procedure and an injection syringe was attached to the left arm for (99m)Tc-TF injection during (123)I-BMIPP SPECT. Results & Discussion The phantom study showed only slight (123)I contamination of (99m)Tc at the 10% window setting. The new method separated the (123)I and (99m)Tc energy windows well and neither crosstalk nor scatter correction were needed. Images obtained from dual (simultaneous) acquisition were contaminated, whereas contamination and influence of scattered rays were absent in images obtained by use of the new protocol. These images were thus useful for clinical diagnosis. Conclusion The new protocol is more convenient for patients and might improve the efficiency of detecting myocardial damage. PMID- 21979781 TI - [Field-size Dependence of the Glass Dosimeter in 6 MV Photon Beams]. AB - The postal dose audit using radio-photoluminescence glass dosimeters was begun in November 2007 in order to improve the quality of radiotherapy in Japan. However, the irradiation conditions are now limited to the reference conditions which are 10*10 cm(2) field and 10 cm depth. The application of the glass dosimeters to non reference conditions is strongly desired. This study dealt with the field-size dependence of the glass dosimeter outputs in the 6 MV photon beams of a medical linear accelerator (Varian Clinac21EX). We irradiated glass dosimeters with square field sizes of 5, 7, 10, 13, 16, 20, 23 and 25 cm side lengths at the 10 cm depth of the water equivalent phantom (SSD=90 cm). The outputs were compared with ionization chamber outputs. The ratio of the glass dosimeter outputs to the absorbed dose to water obtained with the ionization chamber increased approximately 1.5% between 5*5 cm(2) and 25*25 cm(2). We have to consider this field-size dependence when we apply the glass dosimeters to non-reference conditions. PMID- 21979782 TI - [Measurements of TMR, Absorbed Dose using Long SSD TBI Dosimetry and Calculation Accuracy of Treatment Planning System]. AB - Over the last 50 years, total body irradiation (TBI) has become widely used in conditioning regimens for the treatment of hematological malignancies prior to bone marrow or peripheral blood stem cell transplantation. Many techniques and prescriptions have been proposed, and the use of a treatment planning system (TPS) may be best in terms of preventing toxicity to normal tissues and insufficient low dose in bone marrow. Since many measurement data in TPS can be applied at source axis distance (SAD) (1 m), absorbed dose at long source surface distance (SSD) calculated by TPS must be verified prior to clinical use. The aim of this study is to evaluate the difference between (1) TMR measured at long SSD (4 m) and TMR at SAD and (2) the absorbed dose measured at long SSD and the absorbed dose calculated by TPS. TMR measured at long SSD agreed with TMR at SAD within 2.0%, while absorbed dose measured at long SSD agreed with that calculated by TPS within 2.5%. These verifications show that the CT-based treatment planning system of TBI can calculate prescription MU within an acceptable tolerance. PMID- 21979783 TI - [Evaluation of Radio-activated Compounds Produced in the Walls and Adjacent Areas of a Small Medical Cyclotron]. AB - According to the (18)O(p, n) (18)F reaction, fast neutrons produced in the target will cause residual radioactivity in a cyclotron itself and in the concrete walls mainly after thermalization of neutrons.As exploratory work prior to decommissioning of a medical cyclotron facility, surface and core samples of the facility's concrete walls were collected after confirming the external radiation was at a low level based on hollow ionization chamber-type survey meter and glass dosimeter measurements. The residual radioactivity in these samples was measured by gamma-spectrometry. Residual radioactivity was detected in all of the components of the cyclotron. In the concrete, eight residual radioactive nuclides were identified. However, radioactivity concentrations of these radionuclides were less than that of (40)K which may exist generally in a natural environment. A clearance level for radioactive solid waste has not been defined nor implemented at present in Japan, and reliable evaluation will be required to minimize radioactive waste at the time of decommissioning. The present results provide basic data for establishment of regulatory guidelines for decommissioning of medical cyclotrons. PMID- 21979784 TI - Gastrointestinal nematode infections in German sheep. AB - The objective of the present study was to determine the prevalence and variation of natural gastrointestinal nematode (GIN) infections in lambs according to birth type, gender and breed based on individual faecal egg counts (FEC) from various regions in Germany. A total of 3,924 lambs (3 to 15 months old) with different genetic backgrounds (Merinoland, German Blackhead Mutton, Rhoen, Texel and Merino long-wool) were individually sampled during the grazing period between 2006 and 2008. Furthermore, pooled faecal samples from each of the farms were cultured in order to differentiate the third-stage larvae of the nematode spp. Sixty-three percent of the lambs were infected with GIN. The infections were mostly low to moderate and involved several nematode species. The Trichostrongylus spp. was the predominant species based on the percentage of larvae in faecal cultures. Only 11.4% of the lambs were free of Eimeria oocysts. Tapeworm eggs were encountered in 13.2% of all samples. The prevalence of GIN infections varied significantly (P < 0.001) among farms. A significantly higher FEC (P < 0.05) was observed in multiple-born lambs when compared with singletons. Moreover, male lambs were more susceptible to infection than females (P < 0.001). No significant differences (P > 0.05) were observed between breeds regarding FEC. Inter-individual variations were higher than inter-breed differences, which may indicate the possibility of selection within these breeds for parasites resistance as described in earlier studies. PMID- 21979785 TI - Eco-epidemiology of Chagas disease in northeastern Brazil: Triatoma brasiliensis, T. pseudomaculata and Rhodnius nasutus in the sylvatic, peridomestic and domestic environments. AB - An entomological survey was carried out in four rural localities situated in the state of Ceara, assessing Chagas disease seroprevalence in man, focusing on the presence of vectors in natural foci contiguous to the domestic and peridomestic environments. Fifty-three Triatoma brasiliensis, nine T. pseudomaculata and 71 Rhodnius nasutus were collected in their natural habitats as far as 10 m from the houses, and 663, 59 and 8 respectively were captured in peridomestic artificial structures, adjacent to the houses, including henhouses, pigpens, corrals, perches and piles of bricks, tiles and wood. Within the households, 37 T. brasiliensis, one specimen of T. pseudomaculata and one of R. nasutus were captured. Overall, Trypanosoma cruzi infection rates were 2.3% for T. brasiliensis and 11.3% for R. nasutus. Despite that the seroprevalence survey in man did not reveal positive results using two serological techniques, natural triatomine habitats are juxtaposed to man-made artificial ecotopes, resulting in overlapping habitats. The contiguity between natural ecotopes and human dwellings increases the interaction between vectors and humans, challenging continuous surveillance and vector control efforts. PMID- 21979786 TI - Consequent effects of the great cormorant (Phalacrocorax carbo sinensis) predation on parasite infection and body condition of common carp (Cyprinus carpio). AB - Lesions ranging from surface wounds to deep tissue wounds caused by cormorant predation were observed on several species of the farmed fish in Pohorelice, Czech Republic. Two-year-old stocked common carp Cyprinus carpio harvested in late March were examined for ectoparasites and endoparasites, injuries extent, and lysozyme concentration in skin mucus. Additionally, three body condition indices were measured. Endoparasite infection occurred only scarcely. Wounded fish were more susceptible to the ectoparasites Gyrodactylus spp. and Dactylogyrus spp. (Monogenea), and Ichthyophthirius multifiliis (Ciliophora). The intensity of infection of other ectoparasites Eudiplozoon nipponicum (Monogenea), Argulus spp. (Branchiura) and trichodinids (Ciliophora) did not significantly differ between wounded and control groups of fish. Lysozyme concentration in fish mucus was significantly higher in wounded fish and was positively associated with both the extent of damaged epithelium and Gyrodactylus spp. abundance. There were no differences in Fulton's condition factor and lipid content in muscle and liver tissues between wounded and non-wounded fish. Higher values of spleen-somatic index in wounded fish corresponded to increased intensity of parasite infection, most likely reflecting changes in immune system of infected fish. Although our results did not show any significant effect of cormorant attacks on fish condition, the wounded fish had significantly higher parasite numbers which could impact the growth or survival of the fish throughout the production season. PMID- 21979787 TI - Completing the puzzle of aurachin biosynthesis in Stigmatella aurantiaca Sg a15. AB - The aurachins are a family of secondary metabolites, with the main members aurachin A, B, C, and D, produced by the myxobacterium Stigmatella aurantiaca Sg a15. These isoprenoid quinoline alkaloids are classified as A-type or C-type aurachins according to the position of the farnesyl residue either at C4 or C3 of the quinoline core, respectively. Previous feeding studies revealed that the C type aurachins are converted to A-type aurachins by late stage tailoring reactions. While the core gene cluster coding for the functionalities required for the biosynthesis of the basic structure aurachin D is known, neither of the genes encoding for the successively acting tailoring enzymes was known up to date, which was assumed to be due to a split cluster organisation. Here we describe the identification of a total of five genes, located upstream of the aurachin core cluster and at additional two loci elsewhere in the genome, encoding for the aforementioned functionalities. The generation and evaluation of respective inactivation mutants of S. aurantiaca Sg a15 allowed for the first time to propose an exhaustive model for aurachin biosynthesis. One of the deduced biosynthetic transformations corresponds to a pinacol rearrangement, an unprecedented tailoring reaction in secondary metabolite biosynthesis. PMID- 21979788 TI - Sonic hedgehog is cytoprotective against oxidative challenge in a cellular model of amyotrophic lateral sclerosis. AB - We have previously demonstrated that primary cilia on spinal motor neurons are reduced in G93A SOD1 (mSOD) mice, a mouse model of amyotrophic lateral sclerosis (ALS). Sonic hedgehog (Shh) signaling involves the primary cilium and Shh has been shown to be cytoprotective in models of other neurodegenerative diseases. Thus, the Shh signaling pathway may bear further study in ALS. Accordingly, we established that interference with the Shh pathway (with the Shh antagonist cyclopamine or with miRNA 3245p) sensitized HT22 cells, while augmentation of the Shh pathway (with Shh or the Shh agonist purmorphamine) protected cells against hydrogen peroxide (H2O2) challenge. We ectopically expressed mSOD, human wild type SOD1 (wtSOD), or an empty vector in HT22 cells. Compared to empty vector, wtSOD decreased cell death and mSOD increased cell death in response to H2O2 challenge. Treatment with cyclopamine or miRNA 3245p sensitized all three transfections to H2O2 challenge. Treatment with recombinant human Shh or purmorphamine decreased cell death after H2O2 challenge, an effect more pronounced in mSOD cells. Compared with empty vector, overexpression of wtSOD increased Shh and Gli transcript levels and increased activity in a Gli responsive reporter assay. Overexpression of mSOD did not change Shh transcript levels, but decreased Gli transcript levels, especially Gli3, and reduced activity in a Gli reporter assay. These results suggest that overexpression of mSOD but not wtSOD reduces signaling in the Shh pathway and renders mSOD cells more susceptible to H2O2 challenge, and that treatment with Shh or Shh agonists is cytoprotective to mSOD cells. Shh or Shh agonists merit further consideration as potential therapy in ALS. PMID- 21979789 TI - Plasma clomipramine levels in adult patients with obsessive-compulsive disorder. AB - The aim of this study was to explore the possible relationship between plasma clomipramine and its major metabolite (N-desmethylclomipramine) levels and related parameters, and clinical features in patients with obsessive-compulsive disorder (OCD). Twenty-six outpatients (13 men, 13 women), suffering from OCD were consecutively enrolled in this study. The severity of OCD was assessed by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The measurements were taken after 4 weeks and 6 months from the beginning of the treatment. The drug levels were measured by a high-performance liquid chromatography method developed by us. The correlations between biological and clinical parameters were analyzed by means of Spearman's correlation coefficient. The Mann-Whitney test was used for comparing biological and clinical variables between men and women. The results showed that clomipramine levels were related to the doses at the two assessment times. A significant and positive correlation was detected at the beginning between the N-desmethylclomipramine ratio and the Y-BOCS total score; however, this was true only for men, where the similar correlations were measured also with the Y-BOCS subscale. After 6 months of clomipramine, men showed a significant improvement of the compulsions. These findings would highlight the potential impact of assessing clomipramine plasma levels and their relationships with specific symptoms, as well as the influence of the sex on the drug response. PMID- 21979790 TI - Efficacy of metformin for prevention of weight gain in psychiatric populations: a review. AB - There is uncertainty with regard to the appropriate use of metformin for the prevention and management of second-generation antipsychotic-induced weight gain and metabolic abnormalities. We aim to systematically review the primary literature and to provide recommendations with regard to the use of metformin in psychiatric populations prescribed second-generation antipsychotics. The authors undertook a literature search of Medline, EMBASE, and PsycINFO using the search terms; antipsychotic OR atypical antipsychotic AND weight AND metformin. Narrative review was undertaken without additional statistical analysis. The search provided 198 results from which 10 original research papers were identified: six randomized controlled trials and one open-label study for adults and two randomized controlled trials and one open-label study for children and adolescents. Four meta-analyses were also identified. We concluded that if weight gain occurs after second-generation antipsychotic initiation, despite lifestyle intervention, metformin should be considered. Further studies with adequate statistical power are required to determine the efficacy of metformin in those with chronic psychotic illness. PMID- 21979791 TI - Osteochondritis dissecans. PMID- 21979792 TI - Bacterial cell disruption: a crucial step in protein production. AB - Recombinant protein production significantly improved in the past three decades. Novel expression systems were developed, growth conditions optimised and the technology and thus monitoring and analysis significantly enhanced. However, the studies of bacterial cell disruption were more or less neglected. The existing methods were acceptable until the final product of protein production was soluble and pure protein. However recently, inclusion bodies (IBs) as whole protein particles were also recognised as the final product. Classical methods for bacterial cell disruption are therefore not always suitable, sufficient or even appropriate for isolation of such particulate material. Some of the currently existing methods for bacterial cell disruption were recognised as damaging for the structure of IBs, while sonication was even found harmful for the recombinant protein. The powers needed for disruption of the bacterial cells damage the recombinant proteins and thus their biological activity significantly reduces. Furthermore, the classical isolation methods enable disruption of majority of the bacterial cells and this is enough for isolation of soluble proteins, yet it is not adequate for isolation of particulate material. While remaining bacterial cells sediment together with the IBs, they represent impurity. The need for isolation of cell-free IBs was therefore revealed in the recent studies, because only pure IBs can be used as nanoparticles in further biomedical applications. Therefore it is time to consider, redesign, optimise or even develop new alternative methods that would enable isolation of pure, structurally intact and biologically active particles. Two such alternative methods that enable isolation of bacterial free, active protein particles were developed recently. PMID- 21979793 TI - Endovascular management of the arteria profunda femoralis: long-term angiographic and clinical outcomes. AB - PURPOSE: This study was designed to investigate the long-term angiographic and clinical outcomes of percutaneous transluminal angioplasty (PTA) of the arteria profunda femoralis (PFA), in a series of patients suffering from critical limb ischemia (CLI) or severe intermittent claudication (IC). METHODS: Our department's database was searched to identify patients who underwent PTA or bail out stenting of the PFA. Among the study's inclusion criteria were Rutherford categories 3-6 and >=70% stenosis of the PFA. Only de novo stenotic lesions were assessed. Primary endpoints were technical success, angiographic lesion primary patency, angiographic binary in-lesion restenosis, and target lesion recanalization (TLR) rates. Secondary endpoints included patient survival, limb salvage, and complication rates. Patient's baseline demographics, lesion, and procedural details were analyzed. RESULTS: Between 2001 and 2011, 20 consecutive patients (17 males) with a mean age of 73 +/- 9 (range 53-87) years underwent PTA or bail-out stenting in 23 PFA lesions. Critical limb ischemia was the indication in eight of 20 patients (40%). The mean lesion length was 31 +/- 9.5 mm. The procedural technical success was 100% (23/23), whereas mean time angiographic and clinical follow-up was 26.8 +/- 24.6 months. According to the Kaplan-Meier analysis, primary patency and binary restenosis rate were 95 and 86.1% respectively up to 8 years follow-up. No TLR procedures were performed. The 8 year patient survival and limb salvage rates were 87.5 and 84.7% respectively. CONCLUSIONS: PTA or stenting of focal, stenotic, PFA lesions, in patients suffering from CLI or IC, exhibit high long-term primary patency rates, as well as low binary restenosis and TLR rates. Large, multicenter studies are required to validate these results. PMID- 21979794 TI - Transsinusoidal portal vein embolization with ethylene vinyl alcohol copolymer (Onyx): a feasibility study in pigs. AB - PURPOSE: Portal vein embolization is performed to increase the future liver remnant before liver surgery in patients with liver malignancies. This study assesses the feasibility of a transsinusoidal approach for portal vein embolization (PVE) with the ethylene vinyl alcohol copolymer, Onyx. METHODS: Indirect portography through contrast injection in the cranial mesenteric artery was performed in eight healthy pigs. Onyx was slowly injected through a microcatheter from a wedged position in the hepatic vein and advanced through the liver lobules into the portal system. The progression of Onyx was followed under fluoroscopy, and the extent of embolization was monitored by indirect portography. The pigs were euthanized immediately (n = 2), at 7 days (n = 4), or at 21 days postprocedure (n = 2). All pigs underwent necropsy and the ex vivo livers were grossly and histopathologically analyzed. RESULTS: Transsinusoidal PVE was successfully performed in five of eight pigs (63%). In 14 of 21 injections (67%), a segmental portal vein could be filled completely. A mean of 1.6 liver lobes per pig was embolized (range 1-2 lobes). There were no periprocedural adverse events. Focal capsular scarring was visible on the surface of two resected livers, yet the capsules remained intact. Histopathological examination showed no signs of recanalization or abscess formation. Mild inflammatory reaction to Onyx was observed in the perivascular parenchyma. CONCLUSIONS: The porcine portal vein can be embolized through injection of Onyx from a wedged position in the hepatic vein. Possible complications of transsinusoidal PVE and the effect on contralateral hypertrophy need further study. PMID- 21979795 TI - Serial renal biopsy findings in a case of POEMS syndrome with recurrent acute renal failure. AB - This report describes a patient presenting with recurrent acute renal failure occurring in the course of POEMS syndrome, a multisystem disease associated with plasma cell dyscrasia. Several combined immunosuppression therapies failed to resolve recurrent acute renal failure; autologous peripheral blood stem cell transplantation was therefore applied. A renal biopsy was performed on each of four occasions when he developed renal dysfunction. The renal biopsy showed typical renal histology of POEMS, membranoproliferative glomerulonephritis-like lesions and narrowing of vessel lumina of various sizes caused by endothelial injury, which progressed to glomerulosclerosis and vessel occlusion. Recurrent acute renal failure might be caused by ischemia due to arterial occlusion. Serum levels of vascular epithelial growth factor (VEGF), which is considered to be a causative factor of endothelial lesions in POEMS syndrome, were not elevated throughout the course of this case. PMID- 21979797 TI - Functional characterization of a genetic polymorphism in the promoter of the ESR2 gene. AB - The ESR2 gene encodes the estrogen receptor beta protein. Several studies have shown that genetic variants in the ESR2 gene are associated with a variety of clinical phenotypes. However, very little is known about the functional significance of ESR2 genetic variants. We used a bioinformatics approach to identify regions of the ESR2 promoter that is evolutionarily conserved across the genomes of several species. We resequenced 1.6 kb of the ESR2 gene which included 0.8 kb of the promoter, 0.3 kb of exon ON, and 0.5 kb of the following intron. We identified five single-nucleotide polymorphisms (SNPs) in the ESR2 promoter and one SNP in the intron. Phase analysis indicated that the SNPs likely exist in 11 different haplotypes. Three of the SNPs (rs8008187, rs3829768, rs35036378) were predicted to alter transcription factor binding sites in the ESR2 promoter. All three were detected only in African American subjects. The rs35036378 SNP was in the TATA box and was highly conserved across species. ESR2 promoter reporter assays in LNCaP and SKBR3 cell lines showed that the variant construct containing the rs35036378 SNP allele had approximately 50% less activity relative to the wild-type construct. We conclude that the rs35036378 SNP appears to cause a reduced promoter activity of the ESR2 gene. PMID- 21979796 TI - Rapid, independent, and extensive amplification of telomeric repeats in pericentromeric regions in karyotypes of arvicoline rodents. AB - The distribution of telomeric repeats was analyzed by fluorescence in situ hybridization in 15 species of arvicoline rodents, included in three different genera: Chionomys, Arvicola, and Microtus. The results demonstrated that in most or the analyzed species, telomeric sequences are present, in addition to normal telomeres localization, as large blocks in pericentromeric regions. The number, localization, and degree of amplification of telomeric sequences blocks varied with the karyotype and the morphology of the chromosomes. Also, in some cases telomeric amplification at non-pericentromeric regions is described. The interstitial telomeric sequences are evolutionary modern and have rapidly colonized and spread in pericentromeric regions of chromosomes by different mechanisms and probably independently in each species. Additionally, we colocalized telomeric repeats and the satellite DNA Msat-160 (also located in pericentromeric regions) in three species and cloned telomeric repeats in one of them. Finally, we discuss about the possible origin and implication of telomeric repeats in the high rate of karyotypic evolution reported for this rodent group. PMID- 21979798 TI - Timing of antiretroviral therapy initiation and its impact on disease progression in perinatal human immunodeficiency virus-1 infection. AB - OBJECTIVE: Treatment with highly active antiretroviral therapy (HAART) reduces overall perinatal human immunodeficiency virus (HIV) type 1-related mortality. The effect of timing of HAART initiation on reduction of morbidity is not well defined. We evaluated the association of timing of HAART initiation on progression to moderate or severe disease. METHODS: Retrospective, population based study of 196 perinatally HIV-infected children followed from birth in northern California from 1988 to 2009. RESULTS: Of 196 children, 58% received HAART and were followed for a median of 6.2 years after HAART initiation. HAART use was associated with improved survival to the age of 5 years: no HAART, 50% versus HAART, 88%; P < 0.0001. However, the advantage of initial HAART over mono or dual therapy transitioning to HAART was small and not statistically significant (P = 0.23). Starting HAART before the development of moderate or severe disease delayed the median age of diagnosis of moderate disease from 0.4 years (interquartile range, [0.3-0.8]) without HAART to 3.0 years ([interquartile range, 1.9-5.8]; P < 0.0001) with HAART. HAART initiation after progression to moderate or severe disease was associated with decreased progression to severe disease or death, respectively (moderate to severe: 8% [3/36] with HAART vs. 84% [70/83] with no HAART, P < 0.0001; severe to death: 9% [6/68] with HAART vs. 73% [49/67] with no HAART, P < 0.0001). CONCLUSIONS: In perinatal HIV infection, HAART is associated with delayed progression and reduced mortality regardless of disease severity at HAART initiation. This finding reinforces US guidelines regarding HAART initiation at >1 year of age if children present with most clinical category B diagnoses, regardless of CD4 measurements or plasma HIV RNA level. PMID- 21979799 TI - Increasing adherence for latent tuberculosis infection therapy with health department-administered therapy. AB - Therapy is almost universally recommended for children with latent tuberculosis infection, but long courses of therapy can decrease adherence to drug therapy. The only variable positively associated with adherence to latent tuberculosis infection therapy in our population was health department-assisted administration of drugs (odds ratio, 7.2; 95% confidence interval, 3.8-13.8). PMID- 21979801 TI - Improvement in lung diffusion by endothelin A receptor blockade at high altitude. AB - Lung diffusing capacity has been reported variably in high-altitude newcomers and may be in relation to different pulmonary vascular resistance (PVR). Twenty-two healthy volunteers were investigated at sea level and at 5,050 m before and after random double-blind intake of the endothelin A receptor blocker sitaxsentan (100 mg/day) vs. a placebo during 1 wk. PVR was estimated by Doppler echocardiography, and exercise capacity by maximal oxygen uptake (Vo(2 max)). The diffusing capacities for nitric oxide (DL(NO)) and carbon monoxide (DL(CO)) were measured using a single-breath method before and 30 min after maximal exercise. The membrane component of DL(CO) (Dm) and capillary volume (Vc) was calculated with corrections for hemoglobin, alveolar volume, and barometric pressure. Altitude exposure was associated with unchanged DL(CO), DL(NO), and Dm but a slight decrease in Vc. Exercise at altitude decreased DL(NO) and Dm. Sitaxsentan intake improved Vo(2 max) together with an increase in resting and postexercise DL(NO) and Dm. Sitaxsentan-induced decrease in PVR was inversely correlated to DL(NO). Both DL(CO) and DL(NO) were correlated to Vo(2 max) at sea level (r = 0.41-0.42, P < 0.1) and more so at altitude (r = 0.56-0.59, P < 0.05). Pharmacological pulmonary vasodilation improves the membrane component of lung diffusion in high altitude newcomers, which may contribute to exercise capacity. PMID- 21979803 TI - Inspiratory muscle training lowers the oxygen cost of voluntary hyperpnea. AB - The purpose of this study was to determine if inspiratory muscle training (IMT) alters the oxygen cost of breathing (Vo(2RM)) during voluntary hyperpnea. Sixteen male cyclists completed 6 wk of IMT using an inspiratory load of 50% (IMT) or 15% placebo (CON) of maximal inspiratory pressure (Pi(max)). Prior to training, a maximal incremental cycle ergometer test was performed to determine Vo(2) and ventilation (V(E)) at multiple workloads. Pre- and post-training, subjects performed three separate 4-min bouts of voluntary eucapnic hyperpnea (mimic), matching V(E) that occurred at 50, 75, and 100% of Vo(2 max). Pi(max) was significantly increased (P < 0.05) by 22.5 +/- 8.7% from pre- to post-IMT and remained unchanged in the CON group. The Vo(2RM) required during the mimic trial corresponded to 5.1 +/- 2.5, 5.7 +/- 1.4, and 11.7% +/- 2.5% of the total Vo(2) (Vo(2T)) at ventilatory workloads equivalent to 50, 75, and 100% of Vo(2 max), respectively. Following IMT, the Vo(2RM) requirement significantly decreased (P < 0.05) by 1.5% (4.2 +/- 1.4% of Vo(2T)) at 75% Vo(2 max) and 3.4% (8.1 +/- 3.5% of Vo(2T)) at 100% Vo(2 max). No significant changes were shown in the CON group. IMT significantly reduced the O(2) cost of voluntary hyperpnea, which suggests that a reduction in the O(2) requirement of the respiratory muscles following a period of IMT may facilitate increased O(2) availability to the active muscles during exercise. These data suggest that IMT may reduce the O(2) cost of ventilation during exercise, providing an insight into mechanism(s) underpinning the reported improvements in whole body endurance performance; however, this awaits further investigation. PMID- 21979802 TI - (In)activity-dependent alterations in resting and reflex control of splanchnic sympathetic nerve activity. AB - The negative effects of sympathetic overactivity on long-term cardiovascular health are becoming increasingly clear. Moreover, recent work done in animal models of cardiovascular disease suggests that sympathetic tone to the splanchnic vasculature may play an important role in the development and maintenance of these disease states. Work from our laboratory and others led us to hypothesize that a lack of chronic physical activity increases resting and reflex-mediated splanchnic sympathetic nerve activity, possibly through changes occurring in a key brain stem center involved in sympathetic regulation, the rostral ventrolateral medulla (RVLM). To address this hypothesis, we recorded mean arterial pressure (MAP) and splanchnic sympathetic nerve activity (SSNA) in a group of active and sedentary animals that had been housed for 10-13 wk with or without running wheels, respectively. In experiments performed under Inactin anesthesia, we tested responses to RVLM microinjections of glutamate, responses to baroreceptor unloading, and vascular reactivity, the latter of which was performed under conditions of autonomic blockade. Sedentary animals exhibited enhanced resting SSNA and MAP, augmented increases in SSNA to RVLM activation and baroreceptor unloading, and enhanced vascular reactivity to alpha(1)-receptor mediated vasoconstriction. Our results suggest that a sedentary lifestyle increases the risk of cardiovascular disease by augmenting resting and reflex mediated sympathetic output to the splanchnic circulation and also by increasing vascular sensitivity to adrenergic stimulation. We speculate that regular physical exercise offsets or reverses the progression of these disease processes via similar or disparate mechanisms and warrant further examination into physical (in)activity-induced sympathetic nervous system plasticity. PMID- 21979804 TI - The effect of physiological concentrations of caffeine on the power output of maximally and submaximally stimulated mouse EDL (fast) and soleus (slow) muscle. AB - The ergogenic effects of caffeine in human exercise have been shown to improve endurance and anaerobic exercise performance. Previous work has demonstrated that 70 MUM caffeine (physiological maximum) can directly increase mouse extensor digitorum longus (EDL) muscle power output (PO) in sprintlike activity by 3%. Our study used the work loop technique on isolated mouse muscles to investigate whether the direct effect of 70 MUM caffeine on PO differed between 1) maximally and submaximally activated muscle; 2) relatively fast (EDL) and relatively slow (soleus) muscles; and 3) caffeine concentrations. Caffeine treatment of 70 MUM resulted in significant improvements in PO in maximally and submaximally activated EDL and soleus (P < 0.03 in all cases). For EDL, the effects of caffeine were greatest when the lowest, submaximal stimulation frequency was used (P < 0.001). Caffeine treatments of 140, 70, and 50 MUM resulted in significant improvements in acute PO for both maximally activated EDL (3%) and soleus (6%) (P < 0.023 in all cases); however, there was no significant difference in effect between these concentrations (P > 0.420 in all cases). Therefore, the ergogenic effects of caffeine on PO were higher in muscles with a slower fiber type (P < 0.001). Treatment with 35 MUM caffeine failed to elicit any improvement in PO in either muscle (P > 0.72 in both cases). Caffeine concentrations below the physiological maximum can directly potentiate skeletal muscle PO. This caffeine induced increase in force could provide similar benefit across a range of exercise intensities, with greater gains likely in activities powered by slower muscle fiber type. PMID- 21979806 TI - High-intensity interval training for health and fitness: can less be more? PMID- 21979805 TI - VO(2) on-kinetics in isolated canine muscle in situ during slowed convective O(2) delivery. AB - The purpose of this study was to examine O(2) uptake (Vo(2)) on-kinetics when the spontaneous blood flow (and therefore O(2) delivery) on-response was slowed by 25 and 50 s. The isolated gastrocnemius muscle complex (GS) in situ was studied in six anesthetized dogs during transitions from rest to a submaximal metabolic rate (~50-70% of peak Vo(2)). Four trials were performed: 1) a pretrial in which resting and steady-state blood flows were established, 2) a control trial in which the blood flow on-kinetics mean response time (MRT) was set at 20 s (CT20), 3) an experimental trial in which the blood flow on-kinetics MRT was set at 45 s (EX45), and 4) an experimental trial in which the blood flow on-kinetics MRT was set at 70 s (EX70). Slowing O(2) delivery via slowing blood flow on-kinetics resulted in a linear slowing of the Vo(2) on-kinetics response (R = 0.96). Average MRT values for CT20, EX45, and EX70 Vo(2) on-kinetics were (means +/- SD) 17 +/- 2, 23 +/- 4, and 26 +/- 3 s, respectively (P < 0.05 among all). During these transitions, slowing blood flow resulted in greater muscle deoxygenation (as indicated by near-infrared spectroscopy), suggesting that lower intracellular Po(2) values were reached. In this oxidative muscle, Vo(2) and O(2) delivery were closely matched during the transition period from rest to steady-state contractions. In conjunction with our previous work showing that speeding O(2) delivery did not alter Vo(2) on-kinetics under similar conditions, it appears that spontaneously perfused skeletal muscle operates at the nexus of sufficient and insufficient O(2) delivery in the transition from rest to contractions. PMID- 21979807 TI - Kinetics of muscle deoxygenation and microvascular PO(2) during contractions in rat: comparison of optical spectroscopy and phosphorescence-quenching techniques. AB - The overarching presumption with near-infrared spectroscopy measurement of muscle deoxygenation is that the signal reflects predominantly the intramuscular microcirculatory compartment rather than intramyocyte myoglobin (Mb). To test this hypothesis, we compared the kinetics profile of muscle deoxygenation using visible light spectroscopy (suitable for the superficial fiber layers) with that for microvascular O(2) partial pressure (i.e., Pmv(O(2)), phosphorescence quenching) within the same muscle region (0.5~1 mm depth) during transitions from rest to electrically stimulated contractions in the gastrocnemius of male Wistar rats (n = 14). Both responses could be modeled by a time delay (TD), followed by a close-to-exponential change to the new steady level. However, the TD for the muscle deoxygenation profile was significantly longer compared with that for the phosphorescence-quenching Pmv(O(2)) [8.6 +/- 1.4 and 2.7 +/- 0.6 s (means +/- SE) for the deoxygenation and Pmv(O(2)), respectively; P < 0.05]. The time constants (tau) of the responses were not different (8.8 +/- 4.7 and 11.2 +/- 1.8 s for the deoxygenation and Pmv(O(2)), respectively). These disparate (TD) responses suggest that the deoxygenation characteristics of Mb extend the TD, thereby increasing the duration (number of contractions) before the onset of muscle deoxygenation. However, this effect was insufficient to increase the mean response time. Somewhat differently, the muscle deoxygenation response measured using near-infrared spectroscopy in the deeper regions (~5 mm depth) (~50% type I Mb-rich, highly oxidative fibers) was slower (tau = 42.3 +/- 6.6 s; P < 0.05) than the corresponding value for superficial muscle measured using visible light spectroscopy or Pmv(O(2)) and can be explained on the basis of known fiber-type differences in Pmv(O(2)) kinetics. These data suggest that, within the superficial and also deeper muscle regions, the tau of the deoxygenation signal may represent a useful index of local O(2) extraction kinetics during exercise transients. PMID- 21979809 TI - Brachial artery transection associated with open elbow dislocation in a 12-year old: a case report. AB - Although acute elbow dislocations are common orthopedic injuries, concomitant neurovascular injury is rare. Brachial artery transection can result from open elbow dislocation and responds well to vascular repair. Rapid evaluation and a high level of suspicion are essential to facilitate immediate treatment. Delay to identify vascular injury after elbow dislocation or reduction can potentially lead to limb ischemia, and potential loss of limb. We present a case of relatively rare transection of the brachial artery, with an accompanying traumatic open elbow dislocation in a 12-year-old boy. PMID- 21979810 TI - Religiosity, alcohol use, and sex behaviors among college student-athletes. AB - College student-athletes tend to consume more alcohol, engage in sex, and report more sex partners than nonathlete students. The current study examined the relationship between religiosity (e.g., influence of religious beliefs and church attendance) and alcohol use and sex behavior among college student-athletes. Most of the student-athletes (n=83) were religious. Influence of religious beliefs was a significant predictor of less alcohol use and less sexual activity (i.e., oral and vaginal sex, number of sex partners). However, increased church attendance was not found to be a protective factor. Findings suggest that religious beliefs may contribute to reduction of alcohol use and sexual risk among college student athletes. Consideration should be given to incorporating religiosity aspects in sexual and alcohol risk-reduction interventions for student-athletes. PMID- 21979812 TI - A Faustian bargain? PMID- 21979811 TI - Multitargeting by curcumin as revealed by molecular interaction studies. AB - Curcumin (diferuloylmethane), the active ingredient in turmeric (Curcuma longa), is a highly pleiotropic molecule with anti-inflammatory, anti-oxidant, chemopreventive, chemosensitization, and radiosensitization activities. The pleiotropic activities attributed to curcumin come from its complex molecular structure and chemistry, as well as its ability to influence multiple signaling molecules. Curcumin has been shown to bind by multiple forces directly to numerous signaling molecules, such as inflammatory molecules, cell survival proteins, protein kinases, protein reductases, histone acetyltransferase, histone deacetylase, glyoxalase I, xanthine oxidase, proteasome, HIV1 integrase, HIV1 protease, sarco (endo) plasmic reticulum Ca(2+) ATPase, DNA methyltransferases 1, FtsZ protofilaments, carrier proteins, and metal ions. Curcumin can also bind directly to DNA and RNA. Owing to its beta-diketone moiety, curcumin undergoes keto-enol tautomerism that has been reported as a favorable state for direct binding. The functional groups on curcumin found suitable for interaction with other macromolecules include the alpha, beta-unsaturated beta-diketone moiety, carbonyl and enolic groups of the beta-diketone moiety, methoxy and phenolic hydroxyl groups, and the phenyl rings. Various biophysical tools have been used to monitor direct interaction of curcumin with other proteins, including absorption, fluorescence, Fourier transform infrared (FTIR) and circular dichroism (CD) spectroscopy, surface plasmon resonance, competitive ligand binding, Forster type fluorescence resonance energy transfer (FRET), radiolabeling, site-directed mutagenesis, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), immunoprecipitation, phage display biopanning, electron microscopy, 1-anilino-8 naphthalene-sulfonate (ANS) displacement, and co-localization. Molecular docking, the most commonly employed computational tool for calculating binding affinities and predicting binding sites, has also been used to further characterize curcumin's binding sites. Furthermore, the ability of curcumin to bind directly to carrier proteins improves its solubility and bioavailability. In this review, we focus on how curcumin directly targets signaling molecules, as well as the different forces that bind the curcumin-protein complex and how this interaction affects the biological properties of proteins. We will also discuss various analogues of curcumin designed to bind selective targets with increased affinity. PMID- 21979813 TI - Acetylation regulates monopolar attachment at multiple levels during meiosis I in fission yeast. AB - In fission yeast, meiotic mono-orientation of sister kinetochores is established by cohesion at the core centromere, which is established by a meiotic cohesin complex and the kinetochore protein Moa1. The cohesin subunit Psm3 is acetylated by Eso1 and deacetylated by Clr6. We show that in meiosis, Eso1 is required for establishing core centromere cohesion during S phase, whereas Moa1 is required for maintaining this cohesion after S phase. The clr6-1 mutation suppresses the mono-orientation defect of moa1Delta cells, although the Clr6 target for this suppression is not Psm3. Thus, several acetylations are crucial for establishing and maintaining core centromere cohesion. PMID- 21979814 TI - Natural immunity. Biodiversity loss and inflammatory diseases are two global megatrends that might be related. PMID- 21979815 TI - Tasty and healthy TR(i)Ps. The human quest for culinary pungency. PMID- 21979816 TI - Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo. AB - How individual components of the vascular basement membrane influence endothelial cell behaviour remains unclear. Here we show that laminin alpha4 (Lama4) regulates tip cell numbers and vascular density by inducing endothelial Dll4/Notch signalling in vivo. Lama4 deficiency leads to reduced Dll4 expression, excessive filopodia and tip cell formation in the mouse retina, phenocopying the effects of Dll4/Notch inhibition. Lama4-mediated Dll4 expression requires a combination of integrins in vitro and integrin beta1 in vivo. We conclude that appropriate laminin/integrin-induced signalling is necessary to induce physiologically functional levels of Dll4 expression and regulate branching frequency during sprouting angiogenesis in vivo. PMID- 21979817 TI - The RIG-I ATPase domain structure reveals insights into ATP-dependent antiviral signalling. AB - RIG-I detects cytosolic viral dsRNA with 5' triphosphates (5'-ppp-dsRNA), thereby initiating an antiviral innate immune response. Here we report the crystal structure of superfamily 2 (SF2) ATPase domain of RIG-I in complex with a nucleotide analogue. RIG-I SF2 comprises two RecA-like domains 1A and 2A and a helical insertion domain 2B, which together form a 'C'-shaped structure. Domains 1A and 2A are maintained in a 'signal-off' state with an inactive ATP hydrolysis site by an intriguing helical arm. By mutational analysis, we show surface motifs that are critical for dsRNA-stimulated ATPase activity, indicating that dsRNA induces a structural movement that brings domains 1A and 2A/B together to form an active ATPase site. The structure also indicates that the regulatory domain is close to the end of the helical arm, where it is well positioned to recruit 5' ppp-dsRNA to the SF2 domain. Overall, our results indicate that the activation of RIG-I occurs through an RNA- and ATP-driven structural switch in the SF2 domain. PMID- 21979819 TI - Hesitation to seek gambling-related treatment among Ontario problem gamblers. AB - OBJECTIVES: This study aimed to examine barriers in seeking help for gambling problems. METHODS: A random digit dialing telephone survey was conducted among adults in Ontario, Canada. Respondents meeting criteria for possible past year gambling problems were asked an open-ended question on why they might hesitate once they had decided to seek help. RESULTS: Of 556 eligible respondents, 47% asserted they would not hesitate to seek help. The most frequently identified possible reasons for hesitation were shame, difficulty acknowledging the problem, and treatment-related issues. Younger gamblers and those with higher problem severity, self-perception of a gambling problem, and past treatment experience were more likely to volunteer shame and treatment-related issues. Gamblers with lower problem severity, no self-perception of a gambling problem, and no history of help seeking more frequently said they would not hesitate to seek help. However, among problem/pathological gamblers, 49% did not self-perceive even a moderate gambling problem; they were more likely than self-perceived problem gamblers in this high severity group to predict no hesitation. CONCLUSIONS: In addition to revealing perceived and objective factors that impede help seeking for gambling problems, the identification of possible barriers may indicate, among some disordered gamblers, awareness of gambling problems and consideration given to possible actions. Both tackling barriers and enhancing problem awareness are necessary components of strategies to provide accessible and timely assistance to those with gambling problems. PMID- 21979818 TI - Mean diffusivity in the amygdala correlates with anxiety in pediatric TBI. AB - Traumatic brain injury (TBI) and orthopedic injury (OI) patients are prone to anxiety and mood disorders. In the present study, we integrated anatomical and diffusion tensor neuroimaging to investigate structural properties of the amygdala and hippocampus, gray matter regions implicated in anxiety and mood disorders. Children and adolescents were evaluated during the late sub-acute phase of recovery following trauma resulting from either moderate to severe TBI or OI. Mean diffusivity (MD) of the amygdala and hippocampus was elevated following TBI. An interaction of hemisphere, structure, and group revealed that MD of the right amygdala was elevated in females with TBI. Self-reported anxiety scores were not related to either volume or microstructure of the hippocampus, or to volume or fractional anisotropy of the amygdala. Left amygdala MD in the TBI group accounted for 17.5% of variance in anxiety scores. Anxiety symptoms may be mediated by different mechanisms in patients with TBI or OI. PMID- 21979820 TI - Lower urinary tract destruction due to ketamine: a report of 4 cases and review of literature. AB - Four young ketamine abusers with lower urinary tract symptoms presented to regional hospitals in Shenzhen, China. Investigations demonstrated contracted bladders and other urinary tract abnormalities. There have been few reports of similar findings in ketamine abusers in the Chinese mainland. We followed up each patient for 1.5 years and their individual treatment strategies are also discussed. PMID- 21979821 TI - Acute care hospital utilization among medical inpatients discharged with a substance use disorder diagnosis. AB - OBJECTIVE: Hospital discharge may be an opportunity to intervene among patients with substance use disorders to reduce subsequent hospital utilization. This study determined whether having a substance use disorder diagnosis was associated with subsequent acute care hospital utilization. METHODS: We conducted an observational cohort study among 738 patients on a general medical service at an urban, academic, safety-net hospital. The main outcomes were rate and risk of acute care hospital utilization (emergency department visit or hospitalization) within 30 days of discharge. The main independent variable was presence of a substance use disorder primary or secondary discharge diagnosis code at the index hospitalization. RESULTS: At discharge, 17% of subjects had a substance use disorder diagnosis. These patients had higher rates of recurrent acute care hospital utilization than patients without substance use disorder diagnoses (0.63 vs 0.32 events per subject at 30 days, P < 0.01) and increased risk of any recurrent acute care hospital utilization (33% vs 22% at 30 days, P < 0.05). In adjusted Poisson regression models, the incident rate ratio at 30 days was 1.49 (95% confidence interval, 1.12-1.98) for patients with substance use disorder diagnoses compared with those without. In subgroup analyses, higher utilization was attributable to those with drug diagnoses or a combination of drug and alcohol diagnoses, but not to those with exclusively alcohol diagnoses. CONCLUSIONS: Medical patients with substance use disorder diagnoses, specifically those with drug use-related diagnoses, have higher rates of recurrent acute care hospital utilization than those without substance use disorder diagnoses. PMID- 21979822 TI - Effects of early postnatal environment on phenotype and survival of a lizard. AB - Nutritional and thermal regimes experienced early in life can strongly influence offspring quality and ultimately adult life histories, especially in ectotherms. However, the importance of the interaction between diet and temperature during postnatal development and the effect on offspring quality are unknown. We compared offspring quality (size, shape, speed, behavior, and survival) of juvenile McCann's skinks (Oligosoma maccanni) housed outdoors under variable thermal conditions (under shelter, but exposed to daily and seasonal variations in light and temperature) with those housed indoors under more stable thermal conditions (controlled temperatures providing 30-40% more basking opportunity) and with a control group (open field conditions). For those caged in captivity (indoors and outdoors), we also compared outcomes between those fed a restricted diet and those fed ad libitum. By comparing individuals raised under different environmental regimes, we aimed to determine whether direct effects of temperature or indirect effects of food supply are more important for offspring quality. Individuals provided with food ad libitum grew faster, and attained larger sizes than those raised on a restricted diet or in the field. Activity rates were higher in individuals exposed to stable rather than variable thermal conditions. Survival post release in the field was highest for larger neonates, and lowest in individuals raised under stable thermal conditions and a restricted diet. We found little evidence for effects of an interaction between feeding and thermal regimes on most factors measured. However, the conditions experienced by young animals (especially diet) do influence important traits for population persistence, such as survival, and may influence key reproductive parameters (e.g., age and size at maturity), which could have implications for conservation management. Further research, including the ultimate influence of early environmental conditions on fecundity and life expectancy, is urgently needed. PMID- 21979823 TI - Screening of peptides bound to breast cancer stem cell specific surface marker CD44 by phage display. AB - CD44, a cancer-associated membrane glycoprotein involved in cell adhesion and tumor progression, has been implicated as a cancer stem cell antigen in several cancers including breast cancer. If the detection sensitivity of CD44 as an early marker for cancer could be improved, this would have important clinical applications. As compared with early stage treatments of other kinds of cancer, treatment of breast cancer is more likely to results in positive outcomes, so this early detection is crucial. Therefore, CD44 is a potential diagnostic target for cancer detection. Herein, we have used a peptide library to screen novel diverse peptides that bind to CD44 with high affinity and characterized the specific binding of these peptides. Our work provides a basis to develop novel diagnostic peptides which may replace antibodies as CD44 detection probes. PMID- 21979824 TI - Effect of total arthroplasty combined with anti-tumor necrosis factor agents in attenuating systemic disease activity in patients with rheumatoid arthritis. AB - We assessed the effect of total large-joint arthroplasty combined with anti-tumor necrosis factor (TNF) therapy for rheumatoid arthritis (RA). We studied 45 RA patients (age 57.91 +/- 12.74 years, RA duration 13.43 +/- 8.28 years) who underwent total arthroplasty (35 knees, 19 hips, 3 elbows, and 1 ankle) between August 2002 and November 2009. All patients received anti-TNF agents (infliximab, 22; etanercept, 33; adalimumab, 3) during the period of the study (that is, they were being treated with the agents when operated on and postoperatively). The disease activity score 28 (DAS28)-erythrocyte sedimentation rate (mean +/- standard deviation) in all patients improved significantly from baseline (just before the operation; 4.32 +/- 0.99) to 1 year after the operation (3.35 +/- 0.93) in contrast with the finding that the mean DAS28-ESR values had remained unchanged from 1 year before the operation to the baseline. Changes in clinical variables in the 58 cases were investigated at baseline, and at 4, 12, and 52 weeks after the operation. The patients were divided by a median split of baseline demographics into 2 groups for further evaluation. Compared with the high-value groups, those with low C-reactive protein and matrix metalloproteinase 3 values showed better results and had lower disease activity. Overall, the DAS28 ESR in both groups had improved 1 year after the operation. In RA patients who are being treated with anti-TNF agents, large-joint arthroplasty may be beneficial, not only for the relief of pain arising from joint destruction, but also for the systemic reduction of RA activity. PMID- 21979826 TI - Revolutionary change in rheumatoid arthritis management with biological therapy. AB - Biological agents targeting a specific molecule have extraordinarily fine specificity and powerful functional capabilities. By the introduction of biological therapy, management of rheumatoid arthritis has undergone a revolution and a paradigm shift. In this review, I will summarize the role in the pathogenesis of rheumatoid arthritis of the molecules targeted by biological agents. Providing evidence obtained in clinical trials and investigator-initiated clinical studies in Japan, the effectiveness and safety of biological therapy in rheumatoid arthritis are discussed. Finally, studies aiming at a personalized strategy with biological agents are listed and the future perspectives toward tailor-made medicine in the field of rheumatology are discussed. PMID- 21979825 TI - Multiscale stochastic modelling of gene expression. AB - Stochastic phenomena in gene regulatory networks can be modelled by the chemical master equation for gene products such as mRNA and proteins. If some of these elements are present in significantly higher amounts than the rest, or if some of the reactions between these elements are substantially faster than others, it is often possible to reduce the master equation to a simpler problem using asymptotic methods. We present examples of such a procedure and analyse the relationship between the reduced models and the original. PMID- 21979827 TI - Neuropeptide effects in the trigeminal system: pathophysiology and clinical relevance in migraine. AB - The neuropeptides substance P, calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) have been considered as important mediators in migraine and other primary headaches. CGRP and VIP have been found at increased concentrations in jugular venous plasma during attacks of migraine or cluster headache, and CGRP receptor antagonists have recently been shown to be effective in migraine therapy. Substance P and CGRP are produced from a subset of trigeminal afferents, whereas VIP derives from parasympathetic efferents. Release of these neuropeptides in the meninges can cause arterial vasodilatation, mast cell degranulation and plasma extravasation in animal experiments, but only CGRP seems to be relevant in migraine. Animal models have confirmed the important role of CGRP in meningeal nociception. The activity of spinal trigeminal neurons is a sensitive integrative measure of trigeminal activity and is partly under the control of CGRP, most likely via central mechanisms. CGRP released from central terminals of trigeminal afferents in the spinal trigeminal nucleus seems to facilitate nociceptive transmission via presynaptic mechanisms. The central effect of CGRP is substantiated by suppression of nociceptive c-fos activation and neuronal activity in the spinal trigeminal nucleus following CGRP receptor inhibition. These proposed functions are supported by the localization of CGRP receptor components in the rat cranial dura mater, trigeminal ganglion and spinal trigeminal nucleus. The currently available data indicate multiple sites of CGRP action in trigeminal nociception and the pathogenesis of migraine; however, central CGRP receptors are likely to be the essential targets in the treatment of migraine using CGRP receptor antagonists. PMID- 21979829 TI - Intraoperative rhabdomyolysis: simulation case scenario. PMID- 21979831 TI - Eating high fat chow increases the sensitivity of rats to 8-OH-DPAT-induced lower lip retraction. AB - Eating high fat food can alter sensitivity to drugs acting on dopamine systems; this study examined whether eating high fat food alters sensitivity to a drug acting on serotonin (5-HT) systems. Sensitivity to (+)-8-hydroxy-2 (dipropylamino) tetralin hydrobromide (8-OH-DPAT; 5-HT1A receptor agonist) induced lower lip retraction was examined in separate groups (n=8-9) of rats with free access to standard (5.7% fat) or high fat (34.3% fat) chow; sensitivity to quinpirole (dopamine D3/D2 receptor agonist)-induced yawning was also examined. Rats eating high fat chow gained more body weight than rats eating standard chow and, after 6 weeks of eating high fat chow, they were more sensitive to 8-OH-DPAT (0.01-0.1 mg/kg)-induced lower lip retraction and quinpirole (0.0032-0.32 mg/kg) induced yawning. These changes were not reversed when rats that previously ate high fat chow were switched to eating standard chow and sensitivity to 8-OH-DPAT and quinpirole increased when rats that previously ate standard chow ate high fat chow. These data extend previous results showing changes in sensitivity to drugs acting on dopamine systems in animals eating high fat chow to a drug acting at 5 HT1A receptors and they provide support for the notion that eating certain foods impacts sensitivity to drugs acting on monoamine systems. PMID- 21979830 TI - The myelin mutants as models to study myelin repair in the leukodystrophies. AB - The leukodystrophies are rare and serious genetic disorders of the central nervous system that primarily affect children who frequently die early in life or have significantly delayed motor and mental milestones that result in long-term disability. Although with some of these disorders, early intervention with bone marrow or cord blood transplantation has been proven useful, it has not yet been determined that such therapies promote myelin repair of the central nervous system. Research on experimental therapies aimed at myelin repair is aided by the ability to test cell replacement strategies in genetic models in which the mutations and neuropathology match the human disorder. Thus, models exist of Pelizaeus-Merzbacher disease and the lysosomal storage disorder, Krabbe disease, which reflect the clinical and pathological course of the human disorders. Collectively, animals with mutations in myelin genes are called the myelin mutants, and they include rodent models such as the shiverer mouse that have been extensively used to study myelination by exogenous cell transplantation. These studies have encompassed many permutations of the age of the recipient, type of transplanted cell, site of engraftment, and so forth, and they offer hope that the scaling up of myelin produced by transplanted cells will have clinical significance in treating patients. Here we review these models and discuss their relative importance and use in such translational approaches. We discuss how grafts are identified and functional outcomes are measured. Finally, we briefly discuss the cells that have been successfully transplanted, which may be used in future clinical trials. PMID- 21979832 TI - Antidepressant-like effects of 3,4-methylenedioxymethamphetamine in an animal model of depression. AB - Increased synaptic serotonin (5-hydroxytryptamine) levels may underlie antidepressant-like effects of 3,4-methylenedioxymethamphetamine (MDMA) that may be more prominent in subjects with mood disturbance. The Flinders Sensitive Line (FSL) strain is an important animal model of depression. These rats are more immobile in the forced swimming test (FST), and their immobility is reversed by known antidepressants after prolonged administration. The objective of this study was to determine whether MDMA administration has a dose-dependent antidepressant like effect in this animal model of depression. The effects of MDMA at 5 and 10 mg/kg following single and repeated administration were assessed in FSL rats using the FST. Sprague-Dawley rats were used as a control. During both FST sessions, saline-treated FSL rats were significantly more immobile than Sprague Dawley rats (P<0.001). Acute MDMA administration had a dose-dependent antidepressant-like effect in FSL rats, which was most evident after 10 mg/kg. This effect was diminished after repeated administration. Methamphetamine 2 mg/kg, which was used as a positive control for locomotor activity induction, did not affect the depressive-like state in FSL rats. There were no changes in the cortical levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid after treatments. It is concluded that MDMA exhibited an antidepressant-like effect in FSL rats, which was most evident following acute administration. PMID- 21979833 TI - Drinking sucrose enhances quinpirole-induced yawning in rats. AB - Food and drugs can activate brain dopamine systems and sensitivity to the effects of drugs acting on those systems is influenced by amount and content of food consumed. This study examined the effects of drinking sucrose on behavioral effects of the direct-acting dopamine receptor agonist quinpirole. Male Sprague Dawley rats (n=6/group) had free access to water or 10% sucrose and quinpirole dose-response curves (yawning and hypothermia) were generated weekly for 8 weeks. Subsequently, all rats drank water for 8 weeks with quinpirole dose-response curves determined on weeks 9, 10, and 16. In rats drinking sucrose, the ascending (D3 receptor-mediated), but not descending (D2 receptor-mediated), limb of the yawning dose-response curve shifted leftward. The D3 receptor-selective antagonist PG01037 shifted the ascending limb of the dose-response curve to the right in all rats. When rats that previously drank sucrose drank water, their sensitivity to quinpirole did not return to normal. Quinpirole-induced hypothermia was not different between groups. These data show that drinking sucrose increases sensitivity to a dopamine D3, but not D2, receptor-mediated effect and that this change is long lasting. Dopamine receptors mediate the effects of many drugs and the actions of those drugs are likely impacted by dietary factors. PMID- 21979834 TI - Behavioral sensitization to 3,4-methylenedioxymethamphetamine is long-lasting and modulated by the context of drug administration. AB - To begin to characterize the temporal profile of behavioral sensitization to the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA), rats were treated with either saline or MDMA (5.0 mg/kg) twice daily for 5 days, followed by a challenge injection of MDMA (2.5 mg/kg) either 15 or 100 days later. Because we found previously that contextual drug associations are important for the expression of behavioral sensitization to MDMA following relatively short withdrawal periods, rats received the repeated injections either in their home cages (unpaired group) or in the activity monitors that were used for testing sensitization on challenge day (paired group). Locomotor sensitization was evident at 15 days of withdrawal but only in the paired MDMA-treated group. Interestingly, however, sensitization was apparent at 100 days of withdrawal in both paired and unpaired rats but the form of sensitization differed between groups. Thus, sensitization in paired rats was expressed as an increase in stereotypy, whereas sensitization in unpaired rats was expressed as an increase in locomotion, paralleling locomotion levels in paired animals at 15 days of withdrawal. These results suggest that the neural changes that underlie behavioral sensitization to MDMA are quite enduring but involve an interaction between withdrawal time and the context of drug administration. PMID- 21979835 TI - Anemia in chronic heart failure: can we treat? What to treat? AB - Even though anemia is a significant comorbidity regularly observed in patients with chronic heart failure (HF), only in recent years systematic therapeutic research has been started. This article aims to review the aspects of anemia in chronic HF that are relevant for making treatment decisions, beginning with the definition of anemia and its incidence and prevalence of anemia in patients with chronic HF. Considering the etiology and prognostic impact of anemia in chronic HF, several treatment options will be considered. The latter are the application of erythropoiesis-stimulating agents (erythropoietin or darbepoetin alfa) or in the application of intravenous iron (e.g., iron carboxymaltose). According to the results seen in the FAIR-HF trial, iron supplementation should be particularly considered to improve symptoms and quality of life. Intravenous iron application may result in higher compliance and much faster treatment response than oral iron. The RED-HF study will show whether use of darbepoetin alfa in anemic patients with chronic HF will reduce the combined endpoint of death for any reason or hospitalization for heart failure. PMID- 21979838 TI - Isoprenoids in three-dimensional space: the stereochemistry of terpene biosynthesis. AB - This review summarises the accumulated knowledge about the stereochemical courses of biosynthetic reactions to isoprenoids. Important pathways of the primary metabolism (mevalonate pathway, deoxyxylulose phosphate pathway) to the monomeric isoprenoid building blocks, the biosynthesis of the oligomeric linear precursors, and reactions to (poly-)cyclic mono-, sesqui-, and diterpenes are discussed. PMID- 21979837 TI - Characterization of rotavirus and norovirus strains: a 6-year study (2004-2009). AB - OBJECTIVE: To monitor rotavirus (RV) and norovirus (NoV) infections in hospitalized children <= 5 years with acute gastroenteritis in the state of Sao Paulo, Brazil, during a 6-year period (2004- 2009). METHODS: This retrospective study was conducted with 61 medical centers with convenient surveillance fecal specimens, investigated by enzyme-linked immunosorbent assay, sodium dodecyl sulfate polyacrylamide gel electrophoresis, reverse polymerase chain reaction and sequencing to genotype characterization. RESULTS: RV and NoV infections were detected in 29.6% (144/487) and 29.2% (26/89) of the samples, respectively. The most frequent RV genotypes detected were G9P[8] in 2004; G1P[8] in 2005; G9P[8] in 2006; and G2P[4] during 2007, 2008, and 2009. Detection rate declined from 36.3% (33/91) in 2004 to 4.2% (4/95) in 2009. NoV genogroup GII was found in 61.6% (16/26) of the samples, and GI in 11.5% (3/26). Mixed NoV-RV infections were observed in 2.2% (2/89) of the samples, involving GI+G9P[8] and GI+G2P[4] strains. CONCLUSIONS: Genotype distribution varied according to collection year, accompanied by a reduction in detection rate. Use of RV vaccine requires implementation of post-marketing surveillance to monitor RV strain diversity and its efficacy against possible new emerging genotypes. NoVs have been increasingly identified as relevant etiological agents among hospitalized children and play an important role in the viral etiology of pediatric acute gastroenteritis in the state of Sao Paulo. PMID- 21979839 TI - A colloidal model system with tunable disorder: solid-fluid transition and discontinuities in the limit of zero disorder. AB - We study a colloidal model system where disorder can be continuously tuned from no disorder--corresponding to a system that can crystallize--to large disorder where geometrical frustration occurs. The model system consists of colloidal particles with screened electrostatic repulsion. They can only move on single lines which are parallel and equidistant to each other. We introduce disorder by modulating the particle line density. The system exhibits a solid-to-fluid transition which we study by the structure factor and the temporal evolution of the mean-square distance of nearest neighbors on neighboring lines. A determining feature is the occurrence of discontinuities when disorder is tuned to zero. We observe that the peak height of the pair correlation function in the solid phase does not extrapolate to the value of the perfect crystal. Similarly, the mean interaction energy and the screening length at which the solid-fluid transition occurs seem to be discontinuous when the limit of zero disorder is approached. PMID- 21979840 TI - The Poisson-Helmholtz-Boltzmann model. AB - We present a mean-field model of a one-component electrolyte solution where the mobile ions interact not only via Coulomb interactions but also through a repulsive non-electrostatic Yukawa potential. Our choice of the Yukawa potential represents a simple model for solvent-mediated interactions between ions. We employ a local formulation of the mean-field free energy through the use of two auxiliary potentials, an electrostatic and a non-electrostatic potential. Functional minimization of the mean-field free energy leads to two coupled local differential equations, the Poisson-Boltzmann equation and the Helmholtz Boltzmann equation. Their boundary conditions account for the sources of both the electrostatic and non-electrostatic interactions on the surface of all macroions that reside in the solution. We analyze a specific example, two like-charged planar surfaces with their mobile counterions forming the electrolyte solution. For this system we calculate the pressure between the two surfaces, and we analyze its dependence on the strength of the Yukawa potential and on the non electrostatic interactions of the mobile ions with the planar macroion surfaces. In addition, we demonstrate that our mean-field model is consistent with the contact theorem, and we outline its generalization to arbitrary interaction potentials through the use of a Laplace transformation. PMID- 21979836 TI - Angiogenic therapy for cardiac repair based on protein delivery systems. AB - Cardiovascular diseases remain the first cause of morbidity and mortality in the developed countries and are a major problem not only in the western nations but also in developing countries. Current standard approaches for treating patients with ischemic heart disease include angioplasty or bypass surgery. However, a large number of patients cannot be treated using these procedures. Novel curative approaches under investigation include gene, cell, and protein therapy. This review focuses on potential growth factors for cardiac repair. The role of these growth factors in the angiogenic process and the therapeutic implications are reviewed. Issues including aspects of growth factor delivery are presented in relation to protein stability, dosage, routes, and safety matters. Finally, different approaches for controlled growth factor delivery are discussed as novel protein delivery platforms for cardiac regeneration. PMID- 21979842 TI - Diagnosis of long-term sequelae after low-voltage electrical injury. AB - The purpose of this study was to determine the efficacy of diagnostic tests and specialty consultations in aiding the diagnosis of long-term symptoms after low voltage electrical injury (EI). A retrospective hospital chart review of low voltage electrical-injured patients admitted to the outpatient burn clinic of a rehabilitation hospital was conducted (January 2002 to March 2006). Results of tests and specialty consultations were compared between patients with low-voltage contact injuries and patients with low-voltage flash injuries using Student's t test and chi(2) with a P < .05 considered significant. Forty patients were treated for low-voltage EI, and all injuries occurred at work. Three patients were excluded due to lack of exact voltage documentation. Of the remaining 37 patients, there were 31 males (83.8%) and 6 females (16.2%) with a mean age of 36.7 +/- 11.0 years and a mean TBSA of 7.7 +/- 7.3%. Of 83 specialty consultations, the most frequents were psychology (38.6%), physiatry (21.7%), neurology (15.7%), and orthopedic (8.4%). Eighty percent of consultations were negative (no pathology). Patients with electrical contact injury had more specialty consultations (68.7 vs 31.3%, P = .003), especially neurology (21.1 vs 3.8%, P = .027), and more tests than patients with electrical flash injury (86.5 vs 13.5%, P < .001). Four (6.3%) CT scans and 14 (21.9%) magnetic resonance imaging scans were performed in electrical contact injury patients, but the majority of their results were negative (75 and 71.4%, respectively). Ultrasound, bone scan, and x-rays were negative: 80, 100, and 100%, respectively. Low-voltage electrical-injured patients are frequently referred for specialty consultations and tests, which are usually not effective to correlate their long-term symptoms with the initial EI. PMID- 21979841 TI - Risk factors for outbreaks of multidrug-resistant Klebsiella pneumoniae in critical burn patients. AB - The objective of this study is to identify the risk factors related to colonization or infection in an outbreak of multidrug-resistant Klebsiella pneumoniae in a burn patient unit. The authors studied the risk factors associated with colonization or infection using a case-control study design involving patients with multidrug resistant K. pneumoniae (n = 26) and controls (n = 50). They describe the outbreak and provide a retrospective analysis that encompasses patient demographics, microbiological isolation, culture sites, burn features, inhalation injury, biomarkers (lactate and N-terminal probrain natriuretic peptide), general illness severity scores (Acute Physiology and Chronic Health Evaluation II and Sepsis-related Organ Failure Assessment), burn specific severity scores such as the Abbreviated Burn Severity Index (ABSI), length of stay, and mortality. Patients colonized with multidrug-resistant K. pneumoniae were older (55 vs 42 years), presented with larger burns (32 vs 18% of BSA), and more frequently had full-thickness burns (53 vs 22%). They also had higher ABSI, Acute Physiology and Chronic Health Evaluation II, and Sepsis related Organ Failure Assessment scores, and they required more days of mechanical ventilation and longer stays in the critical burn unit. Multivariate analysis showed that the factors most significantly related to the development of infection or colonization with K. pneumoniae were burns located on head and neck (odds ratio, 4.81) and the ABSI score (odds ratio, 1.66). Control of the outbreak was achieved by enforcing contact precautions and extensive cleaning. An elevated ABSI score and burns located on the head and neck were the risk factors most significantly related to colonization or infection in an outbreak of multidrug resistant K. pneumoniae in a critical burn patient unit. PMID- 21979843 TI - Multiple organ failure as a cause of death in patients with severe burns. AB - The aim of this study was to investigate the causes of death in patients with burns using both medicolegal autopsy reports and clinical data collected during treatment to specify irreversible organ dysfunctions leading to death. Burn deaths occurring in the Helsinki Burn Center from 1995 to 2005 were identified in the hospital database. The clinical charts and medicolegal autopsy reports were retrieved and compared. The data were evaluated by plastic surgeons specialized in burn care, an intensivist, and a pathologist, with special reference to organ specific changes in the autopsy reports. From 1999 to 2005, there were 71 burn deaths in the Helsinki Burn Center of which 40% was caused by multiple organ failure (MOF). Death from untreatable burn injury was recorded in 28 patients, whereas other causes were scarce. MOF patients displayed approximately four organ failures on average, ranging from three to eight. All 28 MOF patients were recorded to have acute renal failure, followed by liver damage, of which four patients had acute or chronic liver failure. Sepsis was always affiliated with MOF as a cause of death. In conclusion, careful examination of MOF as a cause of death revealed several organ failures: four organ failures per patient. Acute renal failure was noted in all MOF patients. Sepsis was always affiliated with MOF. PMID- 21979844 TI - The use of bioelectric dressings in skin graft harvest sites: a prospective case series. AB - Despite advances in wound care treatments for the management of acute and chronic wounds, there remains an unmet need for interventions that accelerate epithelialization. Many authors in the past have advocated the use of electric currents to accelerate wound healing. Novel wound dressings with inherent electric activity are emerging, and studies of these specific modalities are lacking. The principal aim of this study is to evaluate the impact of a bioelectric dressing on acute wound healing. Thirteen patients who underwent skin grafting were enrolled. One half of all skin graft donor sites were treated with the bioelectric dressing and semi-occlusive dressing (SOD) and the other half using solely a SOD. Epithelialization was rated by a blinded burn surgeon attending. Participants also provided a self-assessment of their scar appearance. At week 1 postprocedure, average epithelialization of 71.8% was noted on the bioelectric dressing-treated side, compared with 46.9% on the SOD side, representing an average 34.62% faster wound healing (P = .015). At 1 month, patients rated the bioelectric dressing-treated half as superior in terms of scar color (P = .198), stiffness (P = .088), thickness (P = .038), and overall quality (P = .028). These early data show promise in terms of faster healing, improved scarring, and improved patient subjective outcome with the use of the bioelectric dressing on acute wounds. With fulfillment of an extended study population, the authors hope to provide a solid foundation for extrapolating their data beyond skin graft donor sites to all areas of wound care. PMID- 21979845 TI - Double-blind, randomized, pilot study assessing the resolution of postburn pruritus. AB - The objective of this study was to evaluate whether Provase(r), a nonprescription moisturizer with a blend of protease enzymes, would reduce postburn itching in adult burn survivors relative to a control moisturizer. This was a prospective, single-center, double-blinded, pilot study where 23 burn survivors were randomized to either the treatment group, who applied Provase, or the control group, who applied the base moisturizer used in Provase every 8 hours for 4 weeks. Twelve were randomized to the treatment and 11 to the control groups with 9 participants in each group completing the study. There was no difference between groups with respect to gender, ethnicity, causative factor, TBSA burned, or time postinjury. Participant's pruritus and scar were reevaluated on a weekly basis for 4 consecutive weeks. Relative to baseline, there was a significant reduction of itch duration in minutes at weeks 3 and 4, the number of days per week that itch was experienced at weeks 2, 3, and 4, and the number of itch episodes per day at week 2 for the treatment group. The itch TBSA reduced significantly relative to baseline for the treatment group at week 1, 2, and 3. The affective itch characteristics were significantly reduced for the treatment group for bothersome at weeks 1, 2, 3, and 4; for annoying at week 4; and for unbearable at weeks 2, 3, and 4. Although this was a pilot study and not powered for statistical differences, there were statistically significant differences for itch duration, weekly frequency, itch episodes per day, itch TBSA, and reported affective burden of itch after treatment. Further investigation is recommended with a larger sample size treated for a longer period of time where participants are stratified based on acute or chronic itch. PMID- 21979846 TI - Evaluation of Ki-67 as a histological index of burn damage in a swine model. AB - Histological diagnosis of burn depth lacks consensus. The purpose of this study was to determine whether Ki-67, a cell proliferation marker, provides an index of integument viability after burn injury. Induction of thermal burn injuries (3, 12, 20, 30, 75, 90, and 120 seconds) were made with a brass rod heated to 100 degrees C on the dorsal trunk of the swine. Controls were created with a brass rod heated to 37.5 degrees C. Four 6-mm biopsies were obtained from each site for histological analysis of Ki-67. Biopsies were taken at the following times postinjury: 1, 12, 24, 36, 48, 72, and 96 hours. The results illustrate a characteristic Ki-67 nuclear staining in the basal layer of the epidermis and in the hair follicle. With increasing thermal injury, the nuclei of the cells changed morphology: condensing, fragmenting, and elongating. The uniqueness of the labeling index was to include only morphologically intact nuclei as having capacity to proliferation. Quantitative analysis showed a reduction in the mean number of Ki-67-positive cells, suggesting a reduced regenerative capacity. This study supports using this index as a means of performing histology for burn depth analysis. In future studies, determining viability of partial-thickness burns will require multiple histological markers such as Ki-67 in addition to hematoxylin and eosin staining. PMID- 21979847 TI - High-frequency oscillatory ventilators in burn patients: experience of Riley Hospital for Children. AB - The objective of the study is to review a single institution's experience with high-frequency oscillatory ventilation (HFOV) and compare patient characteristics, outcomes, and complications with other reported studies of HFOV use in burn patients with acute respiratory distress syndrome and respiratory failure. This study is a retrospective chart review of the burn patients treated with HFOV in Pediatric Burn Unit at Riley Hospital for Children from October 1996 to April 2007. Patient data were collected, including demographics, percentage of TBSA burn, percentage of full-thickness burn, mechanisms of burn, settings on conventional mechanical ventilation and HFOV, and blood gas data before initiation of HFOV and at 1, 3, 6, 12, 24, 72 (3 days), 120 (5 days), 168 (7 days), 240 (10 days), and 336 hours (14 days). Length of stay, mortality, and complications were also included. HFOV was used 24 times in 21 patients between October 1996 and April 2007 with a mean age of 10 +/- 11 years. At initiation of HFOV, the PaO2/FiO2 and oxygenation index values were 109 +/- 26 and 36 +/- 12, respectively. At stop, the PaO2/FiO2 improved to 166 +/- 24 with an average increase from before HFOV of 57 +/- 39 (P < .002). At 5 days of HFOV, oxygenation index improved to 14.1 +/- 1.7 (P < .02) but did not significantly improve at discontinuation of HFOV at 28.8 +/- 6.2 (P = .11). The mortality rate during admission to the burn unit was 29%. Barotrauma occurred in 38% of patients during HFOV. Severe hypercapnea was present briefly in 49% of patients, and this was refractory to standard treatment in 19%. In our experience, HFOV in severe burn patients has significant, early, and sustained improvement in oxygenation. Earlier institution of HFOV seems to significantly lower rates of barotraumas. PMID- 21979848 TI - Creation and validation of a simple venous thromboembolism risk scoring tool for thermally injured patients: analysis of the National Burn Repository. AB - Venous thromboembolism (VTE) has been identified as a major patient safety issue. The authors report their use of the National Burn Repository (NBR) to create and validate a weighted risk scoring system for VTE. Adult patients with thermal injury from the NBR admitted between 1995 and 2009 were included. Independent variables were either known or could be derived at the time of admission, including TBSA burned, inhalation injury, gender, and age. The dependent variable was VTE, a composite variable of patients with deep venous thrombosis, and pulmonary embolus. The dataset was split into working and validation sets using a random number generator. Multivariable logistic regression identified independent predictors. beta-coefficients for independent predictors were used to generate a weighted risk score. The NBR contained 22,618 patients who met inclusion criteria. The working and validation sets were not statistically different for demographics or risk factors. In the working set, the presence of inhalation injury and increased TBSA were independent predictors of VTE. Adjusted beta coefficients were used to generate a weighted risk score, which showed excellent discrimination for VTE in both the working (c-statistic 0.774) and the validation (c-statistic 0.750) sets. As risk score increased, a linear increase in observed VTE rate was demonstrated in both working and validation sets. The authors have created and validated a simple risk score model to predict VTE risk in thermally injured patients using the NBR. The model is based on risk factors that are easily identified during initial patient contact. PMID- 21979849 TI - Acquired inpatient risk factors for venous thromboembolism after thermal injury. AB - Acquired, in-hospital risk factors that contribute to venous thromboembolism (VTE) risk after thermal injury remain unknown. The authors performed a retrospective, matched case-control study to examine associations between acquired, in-hospital risk factors and development of VTE. They identified thermally injured patients who were diagnosed with VTE over an 8.5-year period at our institution. VTE patients were matched 2:1 with non-VTE controls based on age, TBSA burned, and presence of inhalation injury. Retrospective chart review identified recognized VTE risk factors such as infectious complications, operative procedures, or central venous access. For each VTE patient and their matched controls, data analysis was limited to the time period before VTE developed. This allowed examination of differences in the pre-VTE hospital course between patients with and without VTE. Nineteen patients with VTE were matched 2:1 with non-VTE controls. No significant differences were present between groups for age, gender, TBSA, inhalation injury, body mass index, ventilator days, and intensive care unit or hospital length of stay. Patients with VTE had significantly more operations (3.7 vs 1.9, P = .038), were more likely to have pneumonia (73.7 vs 43.2%, P = .031), or have central venous line insertion (84.2 vs 51.4%, P = .016) in the pre-VTE period. No significant differences were present for positive blood cultures, urinary tract infections, or burn wound infection between groups. Our study demonstrates that number of operations, pneumonia, and central venous access are significantly associated with VTE after thermal injury. These in-hospital risk factors should be incorporated into future risk assessment models. PMID- 21979850 TI - Firefighter burn injuries: predictable patterns influenced by turnout gear. AB - Approximately 100 firefighters suffer fatal injuries annually and tens of thousands receive nonfatal injuries. Many of these injuries require medical attention and restricted activity but may be preventable. This study was designed to elucidate etiology, circumstances, and patterns of firefighter burn injury so that further prevention strategies can be designed. In particular, modification of protective equipment, or turnout gear, is one potential strategy to prevent burn injury. An Institutional Review Board-approved retrospective review was conducted with records of firefighters treated for burn injury from 2005 to 2009. Data collected included age, gender, TBSA, burn depth, anatomic location, total hospital days per patient, etiology, and circumstances of injury. Circumstances of injury were stratified into the following categories: removal/dislodging of equipment, failure of equipment to protect, training errors, and when excessive external temperatures caused patient sweat to boil under the gear. Over the 4 year period, 20 firefighters were treated for burn injury. Mean age was 38.9 +/- 8.9 years and 19 of 20 patients were male. Mean burn size was 1.1 +/- 2.7% TBSA. Eighteen patients suffered second-degree burns, while two patients suffered first degree burns. Mean length of hospitalization was 2.45 days. Scald burns were responsible for injury to 13 firefighters (65%). Flame burns caused injury to four patients (20%). Only three patients received contact burns (15%). The face was the site most commonly burned, representing 29% of injuries. The hand/wrist and ears were the next largest groups, with 23 and 16% of the injuries, respectively. Other areas burned included the neck (10%), arm (6.5%), leg (6.5%), knees (3%), shoulders (3%), and head (3%). Finally, the circumstance of injury was evaluated for each patient. Misuse and noncontiguous areas of protective equipment accounted for 14 of the 20 injuries (70%). These burns were caused when hot steam/liquid entered the gear via gaps in the sleeve or face mask. Three patients (15%) received injury due to removal/dislodging of their safety equipment, two patients (10%) suffered their injuries during training exercises when they were not wearing their safety equipment, and the final patient (5%) received burns due to sweat evaporation. Firefighter burn injuries occur to predictable anatomic sites with common injury patterns. Modification and optimization of gear to eliminate gaps that allow steam/hot liquid entry may decrease burn injury. Improving education regarding the use of protective equipment may also be beneficial. PMID- 21979851 TI - The utilization of Nintendo(r) WiiTM during burn rehabilitation: a pilot study. AB - The purpose of this study was to demonstrate feasibility and measure outcomes on pain, anxiety, active range of motion (AROM), function, enjoyment, and presence with the adjunctive use of Nintendo(r) WiiTM (Nintendo of America Inc., Redmond, WA) during acute burn rehabilitation. Participants were alternated and stratified based on the location of burn into Wii or control treatment groups. Joints of interest with limited AROM were the shoulder, elbow, wrist, hip, knee, and ankle. All participants received three consecutive sessions of passive range of motion and predetermined joint-specific exercises. This was followed by either designated Wii games or therapist-chosen interventions (control). The outcomes were compared between groups using t-tests (P < .05) and Cohen's d statistic. Data from 23 participants aged 20 to 78 years were analyzed. The difference in mean slopes suggested that the Wii group experienced less pain (x = -0.97, P = .07) than the control group over time. Overall, trends with anxiety (x = -0.1l, P = .77), AROM (x = 0.55, P = .81), function (x = -0.38, P = .43), and enjoyment (x = 0.09, P = .73) seemed to favor the Wii group. Presence minimally changed between successive treatment sessions for those in the Wii group. Although statistical significance was not reached in any category, feasibility was supported and the overall pattern for outcomes was positive for the Wii group, the most favorable being for pain reduction. Future research with larger sample sizes is warranted to explore best practice with video game technology throughout the continuum of burn rehabilitation with appropriate prescriptions. PMID- 21979853 TI - Reepithelialization of mid-dermal porcine burns after rapid enzymatic debridement with Debrase(r). AB - Reepithelialization of mid-dermal burns is delayed by the presence of a layer of necrotic eschar. The authors hypothesized that rapid selective debridement using an enzymatic bromelain-based preparation, Debrase(r), would speed reepithelialization. Forty mid-dermal burns (2.5 * 2.5 cm) were created on the back and flanks of two anesthetized domestic pigs (25 kg) using an aluminum bar (150 g) preheated in hot water (80 degrees C) and applied for 20 seconds. The burns were randomized to a 4-hour topical application of Debrase(r) (n = 20) or its vehicle (n = 20) followed by daily application of a petrolatum-based triple antibiotic. Wounds were visualized and photographed daily for evidence of reepithelialization. Reepithelialization was considered complete when the entire wound was opaque and dry when blotted with tissue paper. 4-mm full-thickness biopsies were obtained for histological analysis using hematoxylin and eosin staining by a board-certified dermatopathologist masked to the burn therapy at 7, 9, 11, and 13 days after injury. The primary outcome was time to complete reepithelialization of the burns. Secondary outcomes were the percentage of burns that were reepithelialized at days 7, 11, and 13 and the mean percentage reepithelialization on microscopic analysis. A sample of 20 burns in each group had 80% power to detect a 2-day difference in the time to complete reepithelialization (two-tailed, P < .05). Application of Debrase(r), but not the control vehicle, resulted in dissolution of the necrotic upper dermis in all treated burns. The mean time to complete reepithelialization was faster for Debrase(r)-treated (7.4 +/- 0.8 days) than control-treated (9.1 +/- 2.1 days) burns: difference, 1.7 days (95% confidence interval, 0.5-2.9). The percentage of completely reepithelialized Debrase(r)- and control-treated burns were day 7, 65.0 vs 25.0% (P = .02); day 9, 80.0 vs 40.0% (P = .02); and day 11, 100.0 vs 92.0% (P = .45). Treatment of mid-dermal porcine burns with a single topical application of Debrase(r) results in earlier wound reepithelialization. PMID- 21979852 TI - Early pulmonary immune hyporesponsiveness is associated with mortality after burn and smoke inhalation injury. AB - This prospective study aims to address mortality in the context of the early pulmonary immune response to burn and inhalation injury. The authors collected bronchoalveolar lavage fluid from 60 burn patients within 14 hours of their injury when smoke inhalation was suspected. Clinical and laboratory parameters and immune mediator profiles were compared with patient outcomes. Patients who succumbed to their injuries were older (P = .005), had a larger % TBSA burn (P < .001), and required greater 24-hour resuscitative fluids (P = .002). Nonsurvivors had lower bronchoalveolar lavage fluid concentrations of numerous immunomodulators, including C5a, interleukin (IL)-1beta, IL-1RA, IL-8, IL-10, and IL-13 (P < .05 for all). Comparing only those with the highest Baux scores to account for the effects of age and % TBSA burn on mortality, nonsurvivors also had reduced levels of IL-2, IL-4, granulocyte colony-stimulating factor, interferon-gamma, macrophage inflammatory protein-1beta, and tumor necrosis factor-alpha (P < .05 for all). The apparent pulmonary immune hyporesponsiveness in those who died was confirmed by in vitro culture, which revealed that pulmonary leukocytes from nonsurvivors had a blunted production of numerous immune mediators. This study demonstrates that the early pulmonary immune response to burn and smoke inhalation may be attenuated in patients who succumb to their injuries. PMID- 21979855 TI - An open, parallel, randomized, comparative, multicenter study to evaluate the cost-effectiveness, performance, tolerance, and safety of a silver-containing soft silicone foam dressing (intervention) vs silver sulfadiazine cream. AB - An open, parallel, randomized, comparative, multicenter study was implemented to evaluate the cost-effectiveness, performance, tolerance, and safety of a silver containing soft silicone foam dressing (Mepilex Ag) vs silver sulfadiazine cream (control) in the treatment of partial-thickness thermal burns. Individuals aged 5 years and older with partial-thickness thermal burns (2.5-20% BSA) were randomized into two groups and treated with the trial products for 21 days or until healed, whichever occurred first. Data were obtained and analyzed on cost (direct and indirect), healing rates, pain, comfort, ease of product use, and adverse events. A total of 101 subjects were recruited. There were no significant differences in burn area profiles within the groups. The cost of dressing-related analgesia was lower in the intervention group (P = .03) as was the cost of background analgesia (P = .07). The mean total cost of treatment was $309 vs $513 in the control (P < .001). The average cost-effectiveness per treatment regime was $381 lower in the intervention product, producing an incremental cost effectiveness ratio of $1688 in favor of the soft silicone foam dressing. Mean healing rates were 71.7 vs 60.8% at final visit, and the number of dressing changes were 2.2 vs 12.4 in the treatment and control groups, respectively. Subjects reported significantly less pain at application (P = .02) and during wear (P = .048) of the Mepilex Ag dressing in the acute stages of wound healing. Clinicians reported the intervention dressing was significantly easier to use (P = .03) and flexible (P = .04). Both treatments were well tolerated; however, the total incidence of adverse events was higher in the control group. The silver containing soft silicone foam dressing was as effective in the treatment of patients as the standard care (silver sulfadiazine). In addition, the group of patients treated with the soft silicone foam dressing demonstrated decreased pain and lower costs associated with treatment. PMID- 21979856 TI - High-voltage electrical burn of the genitalia, perineum, and upper extremities: the importance of a multidisciplinary approach. AB - High-voltage electrical burns on genitalia and perineal areas are very rare and only sporadic reports are available in the literature with often confusing diagnoses and inconspicuous treatment protocols. Although the surgical treatment of extremities lesions is well established and includes appropriate debridement, temporary wounds coverage, and final adequate soft-tissue reconstruction, management of genital lesions remains controversial and challenging. The authors present a rare case of severe high-voltage electrical injury with involvement of upper extremities and complex lesions localized to the genitalia and perineal region. Treatment required a multidisciplinary approach including the plastic surgery and the urologic and andrologic teams. PMID- 21979857 TI - A stochastic model of autocatalytic reaction networks. AB - Autocatalytic cycles are rather widespread in nature and in several theoretical models of catalytic reaction networks their emergence is hypothesized to be inevitable when the network is or becomes sufficiently complex. Nevertheless, the emergence of autocatalytic cycles has been never observed in wet laboratory experiments. Here, we present a novel model of catalytic reaction networks with the explicit goal of filling the gap between theoretical predictions and experimental findings. The model is based on previous study of Kauffman, with new features in the introduction of a stochastic algorithm to describe the dynamics and in the possibility to increase the number of elements and reactions according to the dynamical evolution of the system. Furthermore, the introduction of a temporal threshold allows the detection of cycles even in our context of a stochastic model with asynchronous update. In this study, we describe the model and present results concerning the effect on the overall dynamics of varying (a) the average residence time of the elements in the reactor, (b) both the composition of the firing disk and the concentration of the molecules belonging to it, (c) the composition of the incoming flux. PMID- 21979859 TI - A susceptible protein by proteomic analysis from Vibrio anguillarum under various environmental conditions. AB - Vibrio anguillarum is a halophilic Gram-negative bacterium causing vibriosis in marine fish and other aquatic animals. Most bacteria have developed strategies to survive in harsh environments, and V. anguillarum also encounters various stresses in seawater and hosts. In this study, we investigated changes in protein expression of V. anguillarum in response to diverse stress conditions of temperature, pH, and NaCl. Proteins were separated by 2D-PAGE, differences in expression patterns under each of the above conditions were observed, and proteins were identified using MALDI-TOF MS/MS. We found an oxidoreductase short chain dehydrogenase/reductase family protein (OSDR), commonly down-regulated under all applied stresses (temperature 15 degrees C, pH 5 or 10, and NaCl 2 M). Analysis at transcriptional level using RT-PCR showed that osdr gene expression was reduced over time under these stress conditions. Among the various stresses, pH 10 was the most effective for reduction of osdr mRNA transcription. Our findings provide a useful candidate protein for detection of environmental change using V. anguillarum. PMID- 21979858 TI - How do I deal with the axilla in patients with a positive sentinel lymph node? AB - OPINION STATEMENT: Optimal management of the axilla in a patient with a positive sentinel node biopsy is not yet defined.These patients usually have Breast Conserving Surgery and receive adjuvant systemic therapy and whole breast radiation.Treatment options for the axilla include: no further surgery with or without radiation completion axillary nodal dissection with or without radiation Radiation options in addition to whole breast radiation include axillary and supraclavicular nodal irradiation regional nodal irradiationincludes supraclavicular and internal mammary nodes Completion axillary dissection has been standard practice in patients with positive sentinel nodes. the number of involved nodes provides prognostic information. theoretically improves local control, but may be obviated by systemic chemotherapy. but avoidance of dissection may not adversely affect locoregional control or survival. dissection has significant morbidity so safe avoidance is desirable. There is little worldwide concordance on the use of radiation: whole breast radiation (commonly used after breast conserving surgery) may radiate the lower axilla supraclavicular radiation is most commonly recommended for patients with four or more nodes but may confer a survival benefit on patients with lower risk disease. adding nodal irradiation reduces local recurrence with only modest toxicity. Adjuvant systemic therapy provides a survival benefit for patients with nodal disease. Most will receive cytostatic chemotherapy containing an anthracycline and a taxane. Hormone therapy is appropriate for estrogen receptor positive disease. The extent to which systemic therapy controls microscopic nodal disease is unknown. Node positive patients should generally receive adjuvant chemotherapy.A small group of patients benefit from specific nodal therapy. Further studies are needed to better identify these patients. PMID- 21979860 TI - Deep sclerectomy with mitomycin C in eyes with failed glaucoma surgery and pseudophakia. AB - PURPOSE: To report outcomes of deep sclerectomy (DS) with intraoperative mitomycin C (MMC) application in eyes with previous failed glaucoma surgery (GS) and/or cataract extraction (CE). PATIENTS AND METHODS: Single-surgeon case series of 82 eyes of 82 patients undergoing DS with MMC. The patients had previous CE with IOL and/or conjunctival GS and treated intraocular pressure (IOP) >18 mm Hg. MMC (0.2 mg/ml) was applied for 2-3 min before scleral flap dissection. Complete success was defined as IOP between 6 and 21 mm Hg or a reduction of 20% from baseline without medications. Reoperation for glaucoma or related complications, or loss of light perception vision was considered as failure. RESULTS: Mean follow-up was 57.7 +/- 22.4 months with 78% of patients completing the 3-year follow-up. Mean IOP decreased from 24.0 mm Hg (22.3-25.6, 95% confidence intervals) to 13.4 mm Hg (12.0-14.2) at 3 years after surgery (P<0.001). There was a significant decrease in the number of glaucoma medications from 2.0 +/- 1 preoperatively, to 0.3 +/- 0.7, 3 years after surgery. Kaplan-Meier cumulative success rates were 85.6% at 1 year, 80.0% at 2 years, and 76% at 3 years. At 3 years, IOP was maintained <19 and 15 mm Hg in 83 and 70% of eyes, respectively. Fourteen eyes (17.1%) had complications. Delayed hypotony (IOP <6 mm Hg) was the commonest complication in five eyes (6.1%). CONCLUSION: DS with MMC appears to be a safe and effective surgical procedure for eyes with previous intraocular surgery. PMID- 21979864 TI - Thrombin as a multi-functional enzyme. Focus on in vitro and in vivo effects. AB - Thrombin is the central protease in the coagulation cascade and one of the most extensively studied of all enzymes. In addition to its recognised role in the coagulation cascade and haemostasis, thrombin is known to have multiple pleiotropic effects, which mostly have been shown only in in vitro studies: it plays a role in inflammation and cellular proliferation and displays a mitogen activity on smooth muscle cells and endothelial cells, predominantly by activation of angiogenesis. In vivo , thrombin effects were examined in animal models of intravenous or intraarterial thrombin infusion. An extensive literature search regarding in vivo data showed that i) thrombin administered as a bolus causes microembolism, ii) thrombin infused slowly at steady-state conditions (up to 1.6 U/kg/min) leads to bleeds but not to intravascular clotting, iii) large quantity of thrombin infused at low rates (0.05 U/kg/min) does not have any measurable effect, and iv) thrombin increases vascular permeability leading to tissue damage. Although several decades of research on thrombin functions have provided a framework for understanding the biology of thrombin, animal and human studies with use of newer laboratory techniques are still needed to confirm the pleiotropic thrombin functions shown in in vitro studies. PMID- 21979863 TI - External limiting membrane and visual outcome in macular hole repair: spectral domain OCT analysis. AB - PURPOSE: To investigate the relationship between postoperative visual acuity and integrity of the external limiting membrane (ELM) and inner segment-outer segment (IS-OS) junction layers, using spectral domain optical coherence tomography (SD OCT), in eyes with macular holes (MHs) following surgical repair. METHODS: Medical charts of MH-operated cases were retrospectively identified and reviewed. The primary outcome measures were best-corrected visual acuity (BCVA) and the status of the ELM and IS-OS lines, using SD-OCT, at 6 weeks and 6 months postoperatively. RESULTS: Sixty-two eyes of 62 patients were included. At 6 weeks following surgery, out of 56 (90.3%) eyes with successful MH closure: 0 eyes showed the combination of disrupted ELM and continuous IS-OS layers; 7 eyes (12.5%) demonstrated continuity of both ELM and IS-OS (ELM(c)/IS-OS(c) group); 29 eyes (51.8%) had continuous ELM with discontinuous IS-OS layers (ELM(c)/IS-OS(d) group); and 20 eyes (35.7%) had discontinuities in both the layers (ELM(d)/IS OS(d) group). The ELM(d)/IS-OS(d) group had the lowest visual gain at 6 months (P = 0.03). At 6 months, a restoration of the integrity of IS-OS layer was observed in 51.7% eyes in the ELM(c)/IS-OS(d) group and in 5% in the ELM(d)/IS-OS(d) group (P = 0.001). CONCLUSIONS: When both ELM and IS-OS layers showed disruptions 6 weeks postoperatively, a significantly worse BCVA was measured at 6 months, compared with the eyes with only IS-OS disruptions, detected 6 weeks following surgery. The integrity of the ELM layer appears to be a critical factor for the restoration of the photoreceptor layer and for predicting a successful visual outcome following MH repair. PMID- 21979862 TI - Emerging techniques to treat corneal neovascularisation. AB - Neovascularisation is a major cause of visual loss in a number of ophthalmic diseases. This review aims to outline the basic regulators of vessel growth in corneal neovascularisation. An understanding of the underlying principles of physiological and pathophysiological vascular development helps to appreciate current approaches to prevent or treat corneal neovascularisation. Options for future interventions will be discussed in the light of recent evidence provided by animal models of corneal neovascularisation. PMID- 21979865 TI - Patterns in early diffusion-weighted MRI in children with haemolytic uraemic syndrome and CNS involvement. AB - OBJECTIVES: Diffusion-weighted imaging (DWI) in children with diarrhoea associated haemolytic uraemic syndrome (D+HUS) and cerebral involvement was evaluated retrospectively. METHODS: DWI within 24 h of onset of neurological symptoms. The apparent diffusion coefficient (ADC) was measured in grey/white matter and correlated with clinical and laboratory findings. RESULTS: DWI was abnormal in all. Abnormal ADC was detected in the supratentorial white matter (6/12) and cortex (1/12), the basal ganglia (5/12), the thalami (4/12), and the cerebellum (1/12). ADC was reduced in 5/12, increased in 4/12, and both in 3/12. Mean serum sodium was lower in patients with DWI abnormalities affecting the white matter (6/12), than in those with basal ganglia/thalamic involvement (6/12). Neurological outcome was normal in 4/11 and abnormal in 7/11, and 1 patient died, outcome did not correlate to either localisation or type of DWI abnormality. CONCLUSIONS: In D+HUS with neurological symptoms, early DWI may reveal abnormal ADC not only in the basal ganglia/thalami, but also in the white matter/cortex. Besides thrombotic microangiopathy, toxic effects of shiga toxin, azotaemia and hyponatraemia / hypoosmolality may be involved in cerebral involvement in children with D+HUS. Findings on early MRI seem not to predict clinical course or outcome. KEY POINTS: * DWI MR imaging may detect early CNS involvement in haemolytic uraemic syndrome * Different pathogenetical mechanisms may contribute to the CNS disease in HUS * Early MRI findings do not seem to allow prediction of clinical outcome. PMID- 21979866 TI - Cryptococcosis in China (1985-2010): review of cases from Chinese database. AB - BACKGROUND: Cryptococcosis is a potential fatal disease, especially in immunocompromised patients. In China, the profile of cryptococcosis is unclear. Therefore, we summarize the epidemiology and therapy of cryptococcosis in china. METHODS: All cases reports about cryptococcosis in China were collected from CBMdisk database (China Biology and Medicine data disc) with key words of cryptococcosis, or cryptococcal infection, or cryptococcus, and case. The features of the cryptococcosis were retrospectively analyzed. RESULTS: There were 1,032 reports about cryptococcosis, including 8,769 cases. Among them, there were 16% patient with AIDS/HIV, and 17% ones without underlying diseases. There were 2,371 cases of CNS infection. Among them of 2,068 cases, the treatment protocols and outcome were clearly described. The percentages of patients who received intrathecal treatment of amphotericin B(AmB), AmB + 5-FC(5-fluorocytosine), AmB + FCZ(fluconazole), and AmB + 5-FU + FCZ in each medication group were 10, 43, 53, and 33%, respectively. The mortalities were significantly lower in the AmB, Amb + 5-FC, AmB + FCZ intrathecal treatment groups compared with their non-intrathecal treatment controls (6% vs. 23%, 25% vs. 35%, 20% vs. 30%, respectively, P < 0.05), but not in the intrathecal AmB + 5-FU + FCZ group (35% vs. 26%, P > 0.05). CONCLUSION: The Chinese cryptococcosis had its own special clinical features, such as more patients without identifiable underlying diseases. Intrathecal injection of amphotericin B was effective treatment method for cryptococcal CNS infection in China. PMID- 21979861 TI - Don't it make my blue eyes brown: heterochromia and other abnormalities of the iris. AB - Eye colour is one of the most important characteristics in determining facial appearance. In this paper I shall discuss the anatomy and genetics of normal eye colour, together with a wide and diverse range of conditions that may produce an alteration in normal iris pigmentation or form. PMID- 21979867 TI - Genotyping and antifungal drug susceptibility of Trichosporon asahii isolated from Chinese patients. AB - As a major pathogenic agent of trichosporonosis, Trichosporon asahii can cause life-threatening infection in immunocompromised patients. In this study, we analyzed the genotypes of the intergenic spacer (IGS) 1 region of the rRNA gene and the antifungal drug susceptibility of eight T. asahii isolates obtained from Chinese patients. Five genotypes were identified from the eight isolates, including three novel genotypes, three genotype 1, and two genotype 4. The eight T. asahii isolates were resistant to amphotericin B, 5-flucytosine, and terbinafine, but were highly sensitive to fluconazole (FLC), itraconazole (ITC), and voriconazole (VRC). The mean minimum inhibitory concentrations (MICs) of FLC and VRC were significantly lower than those reported in most other countries, while that of ITC was slightly higher. Our results suggest that genotypes of the T. asahii isolated from China are different from those of other countries, and azole drugs appeared to be more effective on the Chinese isolates. These results provide new insights into the epidemiology and antifungal treatment for T. asahii. PMID- 21979868 TI - Screen time and physical activity in youth: thief of time or lifestyle choice? AB - BACKGROUND: This study aimed to examine the relationship between screen time and physical activity (PA) in children and adolescents but also to determine specific elements of PA that were most closely associated with screen time. METHODS: We studied a cross-sectional sample of 6176 10.0-15.9 year olds (53% boys, 12.9 +/- 1.5 years) who completed the Physical Activity Questionnaire for Children/Adolescents and reported daily screen time. Differences in total PA and specific elements of PA were examined between groups reporting: < 2 h, 2-4 h, and > 4 h daily screen time. RESULTS: There were significant differences between screen time groups in: total PA, number of bouts of PA reported, after school PA, evening PA and weekend PA (P < .0001). There was a graded, negative association between higher screen time and lower free-time PA. Participants reporting < 2 h screen time were also significantly more active during school lunch breaks than those reporting > 2 h. Boys reporting > 4 h screen time were less active during physical education lessons. CONCLUSIONS: Screen time is significantly and negatively associated with PA in British youth. Screen time may displace active pursuits out of school but is also associated with lower PA during school. Daily screen time should be limited to < 2 h in line with current recommendations. PMID- 21979870 TI - Maintaining patient safety through innovation: an electronic SBAR communication tool. PMID- 21979869 TI - C-reactive protein haplotypes and dispositional optimism in obese and nonobese elderly subjects. AB - BACKGROUND: Chronic low-grade inflammation, characterized by elevated plasma levels of C-reactive protein (CRP), has been inversely associated with dispositional optimism. Using a Mendelian randomization design, this study explores whether CRP haplotypes that determine CRP plasma levels are also associated with dispositional optimism. METHODS: In a sample of 1,084 community dwelling subjects (aged 60-85 years) from three cohort studies (Arnhem Elderly Study, n = 426; Leiden Longevity Study, n = 355; Zutphen Elderly Study, n = 303), six CRP polymorphisms (rs2808628, rs2808630, rs1205, rs1800947, rs1417938, and rs3091244) coding for five common haplotypes were genotyped. The association of CRP haplotypes with CRP plasma levels and dispositional optimism was analyzed using multivariable linear regression models. Subanalyses were stratified by body mass index (BMI >=25 kg/m(2)). RESULTS: CRP haplotypes determined CRP plasma levels (adjusted beta = 0.094, p < 0.001). In the whole group, no association was found between CRP haplotypes and dispositional optimism scores (adjusted beta = 0.02, p = 0.45). In BMI strata, CRP haplotypes were associated with increasing levels of plasma CRP levels (adjusted beta = 0.112; p = 0.002) and lower dispositional optimism levels (adjusted beta = -0.068; p = 0.03) in the obese group only. CONCLUSIONS: These results suggest that genetically increased CRP levels are involved in low dispositional optimism, but only in case of obesity. PMID- 21979871 TI - Hitech education in community college for workforce training. PMID- 21979873 TI - Novel cysteine tags for the sequencing of non-tryptic disulfide peptides of anurans: ESI-MS study of fragmentation efficiency. AB - Mass spectrometry faces considerable difficulties in de novo sequencing of long non-tryptic peptides with S-S bonds. Long disulfide-containing peptides brevinins 1E and 2Ec from frog Rana ridibunda were reduced and alkylated with nine novel and three known derivatizing agents. Eight of the novel reagents are maleimide derivatives. Modified samples were subjected to MS/MS studies on FT-ICR and Orbitrap mass spectrometers using CAD/HCD or ECD/ETD techniques. Procedures, fragmentation patterns, and sequence coverage for two peptides modified with 12 tags are described. ECD/ETD and CAD fragmentation revealed complementary sequence information. Higher-energy collisionally activated dissociation (HCD) sufficiently enhanced y-ions formation for brevinin 1E, but not for brevinin 2Ec. Some novel tags [N-benzylmaleimide, N-(2,6-dimethylphenyl)maleimide] along with known N-phenylmaleimide and iodoacetic acid showed high total sequence coverage taking into account combined ETD and HCD fragmentation. Moreover, modification of long (34 residues) brevinin 2Ec with N-benzylmaleimide or N-(2,6 dimethylphenyl)maleimide yielded high sequence coverage and full C-terminal sequence determination with ECD alone. PMID- 21979874 TI - Mapping local microstructure and mechanical performance around carbon nanotube grafted silica fibres: methodologies for hierarchical composites. AB - The introduction of carbon nanotubes (CNTs) modifies bulk polymer properties, depending on intrinsic quality, dispersion, alignment, interfacial chemistry and mechanical properties of the nanofiller. These effects can be exploited to enhance the matrices of conventional microscale fibre-reinforced polymer composites, by using primary reinforcing fibres grafted with CNTs. This paper presents a methodology that combines atomic force microscopy, polarised Raman spectroscopy, and nanoindentation techniques, to study the distribution, alignment and orientation of CNTs in the vicinity of epoxy-embedded micrometre scale silica fibres, as well as, the resulting local mechanical properties of the matrix. Raman maps of key features in the CNT spectra clearly show the CNT distribution and orientation, including a 'parted' morphology associated with long grafted CNTs. The hardness and indentation modulus of the epoxy matrix were improved locally by 28% and 24%, respectively, due to the reinforcing effects of CNTs. Moreover, a slower stress relaxation was observed in the epoxy region containing CNTs, which may be due to restricted molecular mobility of the matrix. The proposed methodology is likely to be relevant to further studies of nanocomposites and hierarchical composites. PMID- 21979875 TI - Correlation of macular thickness and posterior hyaloid change following bevacizumab and triamcinolone in diffuse diabetic macular edema in middle-aged patients. AB - To compare changes in posterior vitreous detachment (PVD) following intravitreal injection of bevacizumab and triamcinolone in diffuse diabetic macular edema in middle-aged type 2 diabetes patients and to correlate this change with change in central macular thickness (CMT). DESIGN: cross sectional study. Fifteen consecutive patients treated by intravitreal bevacizumab (group A) and ten patients treated by intravitreal triamcinolone (group B). Institutional study carried out by retrospective analysis of patient registers including serial optical coherence tomography (OCT) images at baseline, and after 1 and 4 months. A central macular thickness (CMT) and vitreomacular relationship was noted on OCT. PVD was graded on a linear scale (0-4). Change in grade of PVD was correlated with change in CMT at each follow-up. At month 4, the decrease in mean CMT from baseline was 51.2 MU (P = 0.000) and 45 MU (P = 0.022) in group A and group B, respectively, with no significant difference between the two groups (P = 0.874). A change in grades of PVD from baseline to month 4 was significant in both group A (P = 0.001) and group B (P = 0.004) with no significant difference between the two groups (P = 0.906). A significant correlation between change in PVD and reduction of CMT was observed in group A (P = 0.011) but not in group B (P = 0.315). Both bevacizumab and triamcinolone caused a significant reduction in macular thickness and a significant change in grade of PVD. Change in PVD played an influential role in the reduction of macular thickness following bevacizumab. PMID- 21979876 TI - Management of refractory acute myeloid leukemia: re-induction therapy or straight to transplantation? AB - Patients with primary resistant and relapsed acute myeloid leukemia (AML) are rarely cured without undergoing allogeneic stem cell transplantation. What is currently debated is whether a trial of re-induction chemotherapy prior to transplantation is beneficial. Data from multiple retrospective analyses have shown that pretreatment variables are useful in predicting response to salvage chemotherapy. For patients unlikely to respond, re-induction attempts may be detrimental, leading to added organ toxicity and possible increased tumor resistance. Allogeneic transplantation in the setting of active disease is the alternative strategy. Multiple studies have demonstrated the feasibility of this approach, but cure rates have been low with the use of traditional transplant approaches. Newer strategies employing allogeneic transplantation earlier in patients with relapsed or refractory AML, as well as the incorporation of novel and effective antileukemic agents into the transplant conditioning regimen, may lead to better outcomes. PMID- 21979877 TI - An oncogenic role of miR-142-3p in human T-cell acute lymphoblastic leukemia (T ALL) by targeting glucocorticoid receptor-alpha and cAMP/PKA pathways. AB - MicroRNAs (miRNAs) are a family of 19-24 nucleotide non-coding RNAs with posttranscriptional regulatory functions. The involvement of miRNAs in normal hematopoiesis implies that deregulated miRNAs might contribute to leukemogenesis. To date, although certain miRNAs have been established a clear oncogenic role in hematological malignancies, other individual miRNAs potentially involved in human leukemogenesis still remain elusive. In this report, we showed that miR-142-3p was upregulated in human T-leukemic cell lines and primary T-leukemic cells isolated from T-cell acute lymphoblastic leukemia (T-ALL) patients and its expressive levels were correlated with patients' prognosis. Such an oncogenic role of miR-142-3p could be explained by its targeting cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) and glucocorticoid receptor alpha (GRalpha). High levels of miR-142-3p resulted in low levels of cAMP and weak activity of PKA, thus relieving the inhibitory effect of PKA on T-leukemic cell proliferation. Meanwhile, miR-142-3p decreased GRalpha protein expression by directly targeting the 3'-untranslational region of GRalpha mRNA, leading to glucocorticoid resistance. Transfection of the miR-142-3p inhibitor effectively converted glucocorticoid resistance, because of the resultant increase of GRalpha expression and PKA activity. These findings suggest that miR-142-3p is critical in T-cell leukemogenesis and may serve as a potential therapeutic target in T-ALL patients. PMID- 21979878 TI - Phase 1b trial of atacicept, a recombinant protein binding BLyS and APRIL, in patients with chronic lymphocytic leukemia. PMID- 21979879 TI - Effect of nucleophosmin1 haploinsufficiency on hematopoietic stem cells. PMID- 21979880 TI - Anti-leukemia activity of chaetocin via death receptor-dependent apoptosis and dual modulation of the histone methyl-transferase SUV39H1. AB - Epigenetic deregulation is involved in acute myeloid leukemia (AML) pathogenesis and epigenetic targeting drugs are in clinical trial. Since the first results with histone-deacetylase inhibitors in AML are controversial, novel single and combined treatments need to be explored. It is tempting to combine chromatin targeting drugs. SUV39H1, the main methyl-transferase for lysine 9 tri methylation on histone H3, interacts with oncogenes involved in AML and acts as a transcriptional repressor for hematopoietic differentiation and immortalization. We report here that pharmacological inhibition of SUV39H1 by chaetocin induces apoptosis in leukemia cell lines in vitro and primary AML cells ex vivo, and that it interferes with leukemia growth in vivo. Chaetocin treatment upregulates reactive oxygen species (ROS) production as well as the transcription of death receptor-related genes, in a ROS-dependent manner, leading to death receptor dependent apoptosis. In addition to its direct inhibition by chaetocin, SUV39H1 is indirectly modulated by chaetocin-induced ROS. Accordingly, chaetocin potentiates other anti-AML drugs, in a ROS-dependent manner. The decryption of a dual mechanism of action against AML involving both direct and indirect SUV39H1 modulation represents an innovative read-out for the anticancer activity of chaetocin and for its synergy with other anti-AML drugs, suggesting new therapeutic combination strategies in AML. PMID- 21979881 TI - Role of protein S and tissue factor pathway inhibitor in the development of activated protein C resistance early in pregnancy in women with a history of preeclampsia. AB - Pregnancy increases the risk of venous thromboembolism. Particularly in early pregnancy, the thrombosis risk can be attributed to the changes in coagulation. Elevated thrombin generation and resistance to activated protein C (APC) are likely to contribute to the increased thrombosis risk during pregnancy. We studied changes and the determinants of thrombin generation and APC resistance in the first 16 weeks of gestation in women with history of preeclampsia. Additionally, we investigated the influence of pregnancy-induced haemodilution on the coagulation system. We measured thrombin generation, APC resistance and plasma levels of prothrombin, factor V, factor X, protein S and tissue factor pathway inhibitor (TFPI) in 30 non-pregnant and 21 pregnant women at 8, 12 and 16 weeks of gestation. All participants shared a history of a hypertensive complication in the preceding pregnancy. Thrombin generation and APC resistance were higher at eight weeks of pregnancy than in the non-pregnant state, and progressively increased between eight and 16 weeks of gestation. Changes in the TFPI and protein S levels accounted for ~70% of pregnancy-induced APC resistance. Interestingly, a significant correlation (slope 2.23; 95%CI: 1.56 to 2.91; r= 0.58) was observed between protein Stotal or protein Sfree levels and haematocrit. In conclusion, pregnancy induces a decrease of TFPIfree and protein Sfree levels that attenuates the function of the TFPI and protein C systems and results in elevated thrombin generation and increased APC resistance. Besides, our data suggest that pregnancy-dependent haemodilution may contribute to the decreased peripheral protein S levels. PMID- 21979882 TI - Use of water sources by buffy-headed marmosets (Callithrix flaviceps) at two sites in the Brazilian Atlantic Forest. AB - Many primates are able to satisfy most of their water requirements from the liquid content of their food, but almost all need to visit external water sources during critical periods. The present study analyses the use of water sources in two free-ranging groups of buffy-headed marmosets (Caratinga and RBAR groups) over an annual cycle. At both sites, a large proportion of the days had no visits, and the visitation rate fell by approximately half in the wet season. Differences between sites appear to reflect both contrasts in habitat structure and the composition of the diet. Despite inhabiting a more humid environment, for example, the RBAR group visited water sources on a significantly larger proportion of days than the Caratinga group. While 94.2% of the records for the RBAR group involved bromeliads, this type of source was not recorded at Caratinga, where terrestrial sources were used relatively frequently. Seasonal variation indicates that arboreal sources are preferred over terrestrial ones at both sites, and that rivers are used as a last resort, when other sources are scarce. The use of terrestrial sources involves cautious and coordinated group behaviour, which presumably reflects the perceived predation risk. Overall, the relatively frequent use of watering sites in the RBAR group might be related to its highly fungivorous diet, in comparison with the more typical gummivorous diet of the Caratinga group, although the exact implications of this difference are not clear from the available data. PMID- 21979884 TI - Clinically silent adrenal adenomas - their relation to the metabolic syndrome and to GNB3 C825T gene polymorphism. AB - OBJECTIVES: Aim of the study was to assess the prevalence of C825T GNB3 gene polymorphism in patients with adrenal incidentaloma (AI) as well as its relation to the metabolic syndrome (MS) and cortisol status. SUBJECT AND METHODS: Alltogether 82 subjects (50 patients with AI, mean age 57.9 + 15 years and 32 subjects without AI, mean age 53.8 + 6.9 years) were included in this study. Parameters of glucose and lipid metabolism, serum adiponectin and the single nucleotide polymorphism C825T in GNB3 gene using PCR-RFLP method were examined. To detect subclinical Cushing syndrome an overnight dexamethason test was performed in all patients with AI. RESULTS: Patients with AI had signifcantly higher BMI, HOMA, triacylglycerols (p < 0.05) and significantly lower serum adiponectine (p < 0.05) than controls. There were no significant differences in metabolic parameters between group with and without subclinical Cushing syndrome (SCS). The prevalence of T allele of GNB3 gene in patients with AI was not significantly higher as compared with control group (32% vs. 47%). No significant differences in serum glucose and lipids between carriers of T and C alleles were detected. However carriers of T allele had significantly lower serum adiponectin than those with allele C (p < 0.01). CONCLUSION: We conclude that patients with AI had significantly higher cardiovascular risk factors that is not related to the presence of SCS. Moreover patients with AI and TC or TT genotype have significantly lower serum adiponectin which may be an early symptom of metabolic syndrome in patients with AI. PMID- 21979885 TI - Primary spontaneous pneumothorax and mitral valve prolapse are not associated. AB - BACKGROUND: Mitral valve prolapse (MVP) is a common diagnosis in patients with primary spontaneous pneumothorax (PSP). This description assumes that MVP and PSP might be manifestations of a systemic connective tissue abnormality. The purpose of this study was to determine the prevalence of MVP in PSP patients of Croatian origin and evaluate their relationship with connective tissue disorders. We also examined the prevalence of PSP in patients with primary MVP. METHODS: Thirty-two patients with PSP and without underlying pulmonary disease or connective tissue disease underwent two-dimensional transthoracic echocardiography performed by a certified cardiologist. Echocardiography and demographic features were analyzed using descriptive statistics. We also examined the medical records of 60 patients with primary MVP. RESULTS: MVP was found in none of the 32 patients suffering from PSP. The age, sex, smoking status, body mass index, side, rate, and family history were similar to previous investigations. Likewise, none of the 60 patients with primary MVP ever had PSP. CONCLUSION: By applying an updated definition of MVP, we found no MVP case among PSP patients of Croatian origin. We also found no PSP in the primary MVP group. Ethnicity may influence the occurrence of MVP in PSP patients, and PSP in primary MVP patients. PMID- 21979888 TI - [Fractures of the talus]. AB - Fractures of the neck of the talus are a relatively uncommon fracture of the foot but they have potentially serious complications. This article details the Hawkins classification, operative treatment and indications, and complications of fractures of the neck of the talus. It also discusses the treatment of fractures of the body of the talus and talar head. An English full text version of this article is available at SpringerLink as supplemental. PMID- 21979886 TI - Biodegradable ocular inserts for sustained delivery of brimonidine tartarate: preparation and in vitro/in vivo evaluation. AB - The bioavailability of therapeutic agents from eye drops is usually limited due to corneal barrier functions and effective eye protective mechanisms. Therefore, the current study aims to enhance ocular bioavailability of brimonidine, a potent antiglaucoma drug, through the preparation of ocular inserts. Solvent casting technique was employed to prepare the inserts using polyvinylpyrrolidone K-90 (PVP K-90) as film-forming polymer blended with different viscosity grades of bioadhesive polymers namely hydroxypropyl methycellulose, carbopol, sodium alginate, and chitosan. The prepared ocular inserts were evaluated for various physicochemical parameters, swelling behavior, and in vitro release patterns. Sodium alginate-based ocular inserts revealed the most sustainment in drug release (99% at 6 h), so it was selected for further modifications via coating it, on one side or dual sides, using hydrophobic film composed of either ethylcellulose or Eudragit RSPO. The obtained in vitro release results for the modified ocular inserts revealed that ethylcellulose is superior to Eudragit RSPO in terms of brimonidine release sustainment effect. Ocular inserts composed of 7% PVP K-90, 1.5% low molecular weight sodium alginate with or without ethylcellulose coat were able to sustain the in vitro release of brimonidine. Their therapeutic efficacy regarding intraocular pressure (IOP) lowering effect when inserted in albino rabbits eyes showed superior sustainment effect compared with that of brimonidine solution. Furthermore, due to both the mucoadhesive property and the drug sustainment effect, the one-side-coated ocular insert showed more IOP lowering effect compared with that of its non-coated or dual-side coated counterpart. PMID- 21979889 TI - [Calcaneus fractures]. AB - Fractures of the calcaneus generally occur in the setting of high-energy trauma, resulting in complex, three-dimensionally oriented fracture patterns. Surgical treatment is typically indicated for displaced intra-articular fractures, permitting restoration of calcaneal height, width and overall morphology, in addition to the posterior facet articular surface where possible, and enabling late in situ arthrodesis as a means of salvage in the event of post-traumatic arthritis. The present article briefly discusses our preferred methods for the management of calcaneal fractures. An English full text version of this article is available at SpringerLink as supplemental. PMID- 21979890 TI - [Causes of failed osteosynthesis of ankle fractures]. AB - Ankle fractures are the most common osseous injuries of the lower extremity. In most cases, open reduction and internal fixation is indicated due to fracture dislocation. Operations of the ankle are generally considered classic, standardized, training procedures. An exact reconstruction with correct length and rotation of the joint as well as stabilization of the tibiofibular ligamentous complex is essential. Beside age and gender of the patient, outcome depends on fracture morphology and comorbidities, e. g., osteoporosis, vascular status, neuropathic disorders, and diabetes mellitus. Additional chondral lesions, extensive closed or open soft tissue injuries, and compartment syndrome due to trauma impact can lead to further problems in the postoperative period. Furthermore, iatrogenic complications like fixed malpositions, instabilities, and implant-associated failure of osteosynthesis may also occur. This article illustrates the causes of preventable mistakes and points out options to increase clinical outcome. PMID- 21979891 TI - [Web-based evidence of treatment capacity. An instrument for optimizing the interface between prehospital and hospital management]. AB - BACKGROUND: The outcome of injured patients depends on intrastractural circumstances as well as on the time until clinical treatment begins. A rapid patient allocation can only be achieved occur if informations about the care capacity status of the medical centers are available. Considering this an improvement at the interface prehospital/clinical care seems possible. MATERIAL AND METHOD: In 2010 in Frankfurt am Main the announcement of free capacity (positive proof) was converted to a web-based negative proof of interdisciplinary care capacities. So-called closings are indicated in a web portal, recorded centrally and registered at the local health authority and the management of participating hospitals. RESULTS: Analyses of the allocations to hospitals of all professional disciplines from the years 2009 and 2010 showed an optimized use of the resources. A decline of the allocations by the order from 261 to 0 could be reached by the introduction of the clear care capacity proof system. The health authorities as the regulating body rarely had to intervene (decline from 400 to 7 cases). Surgical care in Frankfurt was guaranteed at any time by one of the large medical centers. CONCLUSION: The web-based care capacity proof system introduced in 2010 does justice to the demand for optimum resource use on-line. Integration of this allocation system into the developing trauma networks can optimize the process for a quick and high quality care of severely injured patients. It opens new approaches to improve allocation of high numbers of casualties in disaster medicine. PMID- 21979892 TI - Expression of dual angiogenic/neurogenic growth factors in human primary brain tumors. AB - Brain tumors, benign or malignant, are characterized by a very high degree of vascularization. Recent accumulating evidence suggests that during development the neuronal wiring follows the same routes as the vasculature and that these two systems may share some of the same factors for guidance. Thus, expression of dual angiogenic/neurogenic growth factors was evaluated by in situ hybridization in human primary brain tumors of three different types, i.e., astrocytomas, oligodendrogliomas, and ependymomas, of increasing grades, in relation with the grade and type of the tumor. For this evaluation we selected vascular endothelial growth factor (VEGF-A) and its receptors VEGF-R1 and VEGF-R2 and the neuropilins 1 and 2 (NRP-1 and NRP-2), which have proangiogenic properties, platelet-derived growth factor (PDGF) receptor-beta (PDGF-Rbeta), which is required for the functional maturation of blood vessels, the ephrins and their Eph receptors, angiotensinogen (AGT) and thrombospondin-2 (TSP-2), which have potential antiangiogenic properties, and netrin-1 (Net-1), which regulates vascular architecture. We show that the expression of the VEGF-NRP system, PDGF-Rbeta, TSP 2, AGT, and Net-1 are differentially regulated, either increased or decreased, in relation with the type and grade of the tumor, whereas regulation of the ephrinB system does not seem to be relevant in these human brain tumors. PMID- 21979893 TI - Novel amplifications in pediatric medulloblastoma identified by genome-wide copy number profiling. AB - Medulloblastoma (MB) is a WHO grade IV, invasive embryonal CNS tumor that mainly affects children. The aggressiveness and response to therapy can vary considerably between cases, and despite treatment, ~30% of patients die within 2 years from diagnosis. Furthermore, the majority of survivors suffer long-term side-effects due to severe management modalities. Several distinct morphological features have been associated with differences in biological behavior, but improved molecular-based criteria that better reflect the underlying tumor biology are in great demand. In this study, we profiled a series of 25 MB with a 32K BAC array covering 99% of the current assembly of the human genome for the identification of genetic copy number alterations possibly important in MB. Previously known aberrations as well as several novel focally amplified loci could be identified. As expected, the most frequently observed alteration was the combination of 17p loss and 17q gain, which was detected in both high- and standard-risk patients. We also defined minimal overlapping regions of aberrations, including 16 regions of gain and 18 regions of loss in various chromosomes. A few noteworthy narrow amplified loci were identified on autosomes 1 (38.89-41.97 and 84.89-90.76 Mb), 3 (27.64-28.20 and 35.80-43.50 Mb), and 8 (119.66-139.79 Mb), aberrations that were verified with an alternative platform (Illumina 610Q chips). Gene expression levels were also established for these samples using Affymetrix U133Plus2.0 arrays. Several interesting genes encompassed within the amplified regions and presenting with transcript upregulation were identified. These data contribute to the characterization of this malignant childhood brain tumor and confirm its genetic heterogeneity. PMID- 21979894 TI - Protein alterations associated with temozolomide resistance in subclones of human glioblastoma cell lines. AB - Temozolomide (TMZ) is the standard chemotherapeutic agent for human malignant glioma, but intrinsic or acquired chemoresistance represents a major obstacle to successful treatment of this highly lethal group of tumours. Obtaining better understanding of the molecular mechanisms underlying TMZ resistance in malignant glioma is important for the development of better treatment strategies. We have successfully established a passage control line (D54-C10) and resistant variants (D54-P5 and D54-P10) from the parental TMZ-sensitive malignant glioma cell line D54-C0. The resistant sub-cell lines showed alterations in cell morphology, enhanced cell adhesion, increased migration capacities, and cell cycle arrests. Proteomic analysis identified a set of proteins that showed gradual changes in expression according to their 50% inhibitory concentration (IC(50)). Successful validation was provided by transcript profiling in another malignant glioma cell line U87-MG and its resistant counterparts. Moreover, three of the identified proteins (vimentin, cathepsin D and prolyl 4-hydroxylase, beta polypeptide) were confirmed to be upregulated in high-grade glioma. Our data suggest that acquired TMZ resistance in human malignant glioma is associated with promotion of malignant phenotypes, and our reported molecular candidates may serve not only as markers of chemoresistance but also as potential therapeutic targets in the treatment of TMZ-resistant human malignant glioma, providing a platform for future investigations. PMID- 21979895 TI - Knowledge scale effects in face recognition: an electrophysiological investigation. AB - Although the amount or scale of biographical knowledge held in store about a person may differ widely, little is known about whether and how these differences may affect the retrieval processes triggered by the person's face. In a learning paradigm, we manipulated the scale of biographical knowledge while controlling for a common set of minimal knowledge and perceptual experience with the faces. A few days after learning, and again after 6 months, knowledge effects were assessed in three tasks, none of which concerned the additional knowledge. Whereas the performance effects of additional knowledge were small, event-related brain potentials recorded during testing showed amplitude modulations in the time range of the N400 component-indicative of knowledge access--but also at a much earlier latency in the P100 component--reflecting early stages of visual analysis. However, no effects were found in the N170 component, which is taken to reflect structural analyses of faces. The present findings replicate knowledge scale effects in object recognition and suggest that enhanced knowledge affects both early visual processes and the later processes associated with semantic processing, even when this knowledge is not task-relevant. PMID- 21979896 TI - Diabetes: a risk factor for glaucoma? PMID- 21979897 TI - The significance of DNA mismatch repair genes in the diagnosis and management of periocular sebaceous cell carcinoma and Muir-Torre syndrome. AB - OBJECTIVE: The aims of this study were to determine the significance of expression of DNA mismatch repair proteins in detecting systemic malignancies in a series of patients with periocular sebaceous cell carcinoma and to determine the clinical characteristics and frequency of Muir-Torre syndrome in this cohort. DESIGN: The study was a retrospective non-comparative interventional case series. PARTICIPANTS: 31 patients with histologically proven sebaceous cell carcinoma of the eyelid participated in the study. METHODS: The authors made use of retrospective chart review and immunohistochemical staining of specimens. MAIN OUTCOME MEASURES: The main outcome measures are as follows: location, tumour size, sites of origin, growth patterns, management, histopathological and immunohistochemical findings, metastasis, other visceral malignancies and mortality. RESULTS: The median age of presentation of the 31 patients in this study was 71 years (range 35-92 years). There was a near-equal gender distribution (M:F-14:17). The average follow-up was 72 months. Seventeen patients had tumours arising from the upper lid, 13 from the lower lid and 1 from the caruncle. Nine patients had clinical Muir-Torre syndrome. Four patients were positive for microsatellite instability complexes and four were negative. Histologically, 14 patients had a high-grade tumour, 13 were intermediate grade and 4 were low grade. Based on the in situ pattern, six patients had a bowenoid pattern, five had both bowenoid and pagetoid patterns and two had a pagetoid pattern. Eighteen patients had no in situ disease detected. Twenty-one patients were alive without disease, and two were alive with disease. Six patients had died, five from other causes and one from the disease. CONCLUSIONS: Visceral malignancies are common in patients with periocular sebaceous cell carcinoma. Approximately one in eight demonstrated a heritable risk for further visceral malignancy through failure to express DNA mismatch repair proteins. Diagnosis of periocular sebaceous cell carcinoma should prompt physicians to search for other associated malignancies. Immunohistochemical characterisation of these sebaceous lesions is useful in identifying increased risk in affected patients and family members. PMID- 21979899 TI - Elevated intraocular pressure in uveitis associated with juvenile idiopathic arthritis-associated uveitis, often detected after achieving inactivity. PMID- 21979898 TI - Detection of retinal nerve fibre layer progression: comparison of the fast and extended modes of GDx guided progression analysis. AB - PURPOSE: To compare detection of retinal nerve fibre layer changes using GDx guided progression analysis (GPA) fast mode (which assumes fixed variability of a reference population) and extended mode (which measures individual variability), and to determine how they compare with photography and conventional visual field based methods for identifying glaucoma progression. METHODS: 172 eyes from 117 participants in the Diagnostic Innovations in Glaucoma Study (12 healthy, 108 glaucoma suspects and 52 glaucoma eyes) with >= 4 GDx VCC visits and >= 3 good quality GDx VCC scans at each visit were included. RESULTS: Agreement between the GDx GPA fast mode and GDx GPA extended mode was limited. The GDx fast mode and extended mode detected 15 and 18 eyes, respectively, as 'likely progression', but only seven of them agreed. The conventional reference standard (stereophotograph based optic disc and/or visual field progression) identified nine eyes as progressing, of which two eyes were also identified by the GDx fast mode and three eyes by the extended mode. In the GDx fast mode, we found that the progression detection varied depending on which two scans were included in the baseline and follow-up images. CONCLUSION: There was limited agreement between the GDx fast mode and the GDx extended mode for progression detection, and between different scans included in the GDx fast mode progression analysis. Longer follow-up is needed to determine the proportion of eyes classified as 'likely progression' by the GDx analysis that are early change and the proportion that are false positive results. PMID- 21979900 TI - The role of pachymetry in primary care as a refinement tool of ocular hypertension and glaucoma referrals. PMID- 21979901 TI - Gender differences in re-epithelialisation time in fungal corneal ulcers. PMID- 21979902 TI - Endothelin-1 production upon polyI:C stimulation of human conjunctival epithelium. PMID- 21979903 TI - Racial disparities in physical and functional domains in women with breast cancer. AB - INTRODUCTION: African-American women are more likely than white women to have functional impairments after breast cancer (BC) surgery; however, no differences were found in self-reported health status surveys at 12+ months postsurgery. PURPOSE: This analysis compared white and African-American BC survivors' (BCS) health status, health-related quality of life, and the occurrence of physical impairments after BC treatment. METHODS: One hundred sixty-six women (130 white, 28 African-American, 8 other) were assessed for impairments preoperatively and at 1, 3, 6, 9, and 12+ months postsurgery. Health status was assessed at 12+ months using the Short Form Health Survey (SF36v2TM). Analysis of variance estimated differences between groups for health status and impairment occurrence. RESULTS: No differences were found between groups for BC type, stage, grade, or tumor size; surgery type; or number of lymph nodes sampled. African-American BCS had more estrogen/progesterone receptor-negative tumors (p < 0.001; p = 0.036) and received radiation more frequently (p = 0.03). More African-American BCS were employed (p = 0.022) and reported higher rates of social activities (p = 0.011) but less recreational activities (p = 0.020) than white BCS. African-American BCS had higher rates of cording (p = 0.013) and lymphedema (p = 0.011) postoperatively. No differences were found in self-reported health status. CONCLUSION: In a military healthcare system, where access to care is ubiquitous, there were no significant differences in many BC characteristics commonly attributed to race. African-American women had more ER/PR-negative tumors; however, no other BC characteristics differed between racial groups. African American women exhibited more physical impairments, although their BC treatment only differed regarding radiation therapy. This suggests that African-American BCS may be at higher risk for physical impairments and should be monitored prospectively for early identification and treatment. PMID- 21979904 TI - Prospective assessment of health-related quality of life in patients with low grade glioma: a single-center experience. AB - PURPOSE: The assessment of Health-Related Quality of Life (HRQoL) in cancer patients has become increasingly important during the past decades. The aim of this study was to evaluate the HRQoL in patients treated for low-grade glioma (LGG). METHODS AND MATERIALS: Forty-three adult patients with LGG were evaluated prospectively between September 2006 and December 2010. We assessed HRQoL at baseline (after surgery before radiotherapy), at the end of radiotherapy and during follow-up (every 3 months for the first 2 years and every 6 months between 2 and 5 years), using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC-C30), Brain Cancer Module-20 (BN 20), Mini Mental State Examination (MMSE) and Hospital Anxiety and Depression Scale (HADS). RESULTS: We demonstrated changes in global score (p = 0.004), and future uncertainty (p < 0.001), communication deficit (p = 0.007), headache (p < 0.001), drowsiness (p = 0.002) and hair loss (p < 0.001), and recall score (p = 0.0029) during follow-up. All complaints of LGG patients showed improvement, except for the hair loss. Although the baseline cognitive function scores was not significantly different, the third-year cognitive function scores of patients who used antiepileptic drugs had lower when compared to patients who did not use (p < 0.001). The baseline and follow-up anxiety and depression scores did not differ significantly. CONCLUSION: Our results suggested that there were improvement in HRQoL in LGG patients during follow-up and antiepileptic drugs had negative effect on cognitive functions. PMID- 21979905 TI - [Which components should living guidelines contain?]. AB - BACKGROUND: Due to rapidly developing knowledge guidelines should be regularly, i.e. annually, checked for validity and amended. METHODS: Exemplified by the S3 guidelines on prostate cancer a contradiction between the need for updating and financial resources can be seen. Because the participating experts have only limited availability, the hurdles in the application procedure linked to bureaucracy should at least be dropped. RESULTS: In the living guidelines on prostate cancer key questions on 13 updating and 5 primary points in question have been formulated and resolved. Examples of updating are imaging, active surveillance and high-intensity focused ultrasound and for primary points, the benefits of new markers and the results of proton therapy. The work, supported by other disciplines, the AZQ (Medical Center for Quality in Medicine) and the BPS (Federal Association of Prostate Self-help) should be finished by September 2011. PMID- 21979906 TI - [Diagnosis prostate cancer: who makes the treatment decision and which treatment is selected? Opinion survey in a prostate cancer patient support group]. AB - BACKGROUND: It is challenging to decide in which way we should care for localized prostate cancer. The current guideline can be accepted as an appropriate foundation. However, there are doubts if guideline recommendations are implemented. RESULTS: The presented opinion survey of prostate cancer support groups shows that we have too many prostatectomies in senior patients. It reveals deficiencies in the guidance of the patients. They are not sufficiently embedded in the process of decision-making. More attention should be paid to initiatives of patient support groups. PMID- 21979907 TI - [Value of nerve growth factor levels in overactive bladder syndrome: alterations after botulinum toxin therapy]. AB - OBJECTIVES: Several studies discussing the pathology of overactive bladder suggested changes in urinary proteins. The neurotrophin "nerve growth factor" (NGF) seems to be an important marker in overactive bladder syndrome (OAB). In this prospectively designed study we evaluated NGF blood levels (sNGF) initially and after injection of botulinum toxin type A (BTX-A) in the detrusor muscle in patients suffering from idiopathic OAB. MATERIALS AND METHODS: Blood samples were obtained from 26 patients (66.5 years, 28-83) with idiopathic OAB. sNGF levels were measured before and 4 weeks after BTX-A treatment by enzyme-linked immunosorbent assay (ELISA). A group of 32 healthy persons with normal bladder function served as controls (41 years, 19-60). sNGF was evaluated in relation to clinical data and the severity of OAB (wet/dry). RESULTS: Significantly higher sNGF levels were detected in patients with OAB compared to the control group (58.8 vs 2.0 pg/ml, p<0.005). Further, sNGF levels were elevated in patients with wet OAB compared to patients with dry OAB (85.0 vs 0.73 pg/ml, p<0.005). Patients > 60 years showed significantly higher sNGF levels (77.2 vs 8.9 pg/ml, p<0.05) compared to younger OAB patients. After BTX-A therapy sNGF levels decreased significantly compared to baseline (p<0.005). CONCLUSION: NGF appears to play a decisive role in OAB. Its use as a biomarker in both the diagnostics and follow up after therapy seems promising. To what extent sNGF can be useful as a biomarker or in therapy monitoring needs to be examined prospectively in a larger population. PMID- 21979908 TI - Self-assembled polymersomes conjugated with lactoferrin as novel drug carrier for brain delivery. AB - PURPOSE: To develop a novel brain drug delivery system based on self-assembled poly(ethyleneglycol)-poly (D,L-lactic-co-glycolic acid) (PEG-PLGA) polymersomes conjugated with lactoferrin (Lf-POS). The brain delivery properties of Lf-POS were investigated and optimized. METHOD: Three formulations of Lf-POS, with different densities of lactoferrin on the surface of polymersomes, were prepared and characterized. The brain delivery properties in mice were investigated using 6-coumarin as a fluorescent probe loaded in Lf-POS (6-coumarin-Lf-POS). A neuroprotective peptide, S14G-humanin, was incorporated into Lf-POS (SHN-Lf-POS); a protective effect on the hippocampuses of rats treated by Amyloid-beta(25-35) was investigated by immunohistochemical analysis. RESULTS: The results of brain delivery in mice demonstrated that the optimized number of lactoferrin conjugated per polymersome was 101. This obtains the greatest blood-brain barrier (BBB) permeability surface area(PS) product and percentage of injected dose per gram brain (%ID/g brain). Immunohistochemistry revealed the SHN-Lf-POS had a protective effect on neurons of rats by attenuating the expression of Bax and caspase-3 positive cells. Meanwhile, the activity of choline acetyltransferase (ChAT) had been increased compared with negative controls. CONCLUSION: These results suggest that lactoferrin functionalized self-assembled PEG-PLGA polymersomes could be a promising brain-targeting peptide drug delivery system via intravenous administration. PMID- 21979909 TI - Fabrication of cisplatin-loaded poly(lactide-co-glycolide) composite microspheres for osteosarcoma treatment. AB - PURPOSE: To reduce the toxicity and achieve a sustainable and controllable release of cisplatin (CDDP). METHODS: CDDP was loaded onto Fe5 (Fe(3+) doped hydroxyapatite at atomic ratio of Fe(added)/Ca(added) = 5%) nanoparticles through surface adsorption. Subsequently, CDDP-loaded Fe5 nanoparticles (CDDP-Fe5) and/or CDDP were encapsulated into poly(lactide-co-glycolide) (PLGA) microspheres using oil-in-water single emulsion. Drug release profiles and degradation behaviors were monitored. RESULTS: CDDP-Fe5 demonstrated a high initial burst (42% on day 1) and short release time (25 days) as CDDP was directly released from Fe5 nanoparticles. CDDP-Fe5 encapsulated within the PLGA microspheres revealed a lower initial burst (23% on day 1) and longer release time (55 days) than CDDP Fe5. Compared with PLGA microspheres containing only CDDP, which showed typical biphasic release manner, microspheres with CDDP-Fe5 and CDDP demonstrated a nearly linear release after the initial burst. Fe5 and CDDP delayed microsphere degradation. All samples became porous, disintegrated, fused, and formed pellets at the end of the study. CONCLUSION: Fe5/PLGA composite microspheres showed favorable CDDP release behavior compared to microspheres composed of polymer alone, suggesting its potential as a new CDDP formulation. PMID- 21979910 TI - The role of catalytic iron in acute kidney injury. PMID- 21979911 TI - Validating the oxford classification of IgA nephropathy. PMID- 21979912 TI - Disaster preparedness for dialysis patients. PMID- 21979913 TI - The dynamic nature of autophagy in cancer. AB - Macroautophagy (referred to hereafter as autophagy) is a highly regulated cellular process that serves to remove damaged proteins and organelles from the cell. Autophagy contributes to an array of normal and pathological processes, and has recently emerged as a key regulator of multiple aspects of cancer biology. The role of autophagy in cancer is complex and is likely dependent on tumor type, stage, and genetic context. This complexity is illustrated by the identification of settings where autophagy acts potently to either promote or inhibit tumorigenesis. In this review, I discuss the underlying basis for these opposing functions and propose a model suggesting a dynamic role for autophagy in malignancy. Collectively, the data point to autophagy as serving as a barrier to limit tumor initiation. Once neoplastic lesions are established, it appears that adaptive changes occur that now result in positive roles for autophagy in malignant progression and in subsequent tumor maintenance. Remarkably, constitutive activation of autophagy is critical for continued growth of some tumors, serving to both reduce oxidative stress and provide key intermediates to sustain cell metabolism. Autophagy is also induced in response to cancer therapies where it can function as a survival mechanism that limits drug efficacy. These findings have inspired significant interest in applying anti autophagy therapies as an entirely new approach to cancer treatment. It is now apparent that aberrant control of autophagy is among the key hallmarks of cancer. While much needs to be learned about the regulation and context-dependent biological functions of autophagy, it seems clear that modulation of this process will be an attractive avenue for future cancer therapeutic approaches. PMID- 21979915 TI - WUSCHEL protein movement mediates stem cell homeostasis in the Arabidopsis shoot apex. AB - WUSCHEL (WUS) is a homeodomain transcription factor produced in cells of the niche/organizing center (OC) of shoot apical meristems. WUS specifies stem cell fate and also restricts its own levels by activating a negative regulator, CLAVATA3 (CLV3), in adjacent cells of the central zone (CZ). Here we show that the WUS protein, after being synthesized in cells of the OC, migrates into the CZ, where it activates CLV3 transcription by binding to its promoter elements. Using a computational model, we show that maintenance of the WUS gradient is essential to regulate stem cell number. Migration of a stem cell-inducing transcription factor into adjacent cells to activate a negative regulator, thereby restricting its own accumulation, is a theme that is unique to plant stem cell niches. PMID- 21979914 TI - Mechanisms and pathways of growth failure in primordial dwarfism. AB - The greatest difference between species is size; however, the developmental mechanisms determining organism growth remain poorly understood. Primordial dwarfism is a group of human single-gene disorders with extreme global growth failure (which includes Seckel syndrome, microcephalic osteodysplastic primordial dwarfism I [MOPD] types I and II, and Meier-Gorlin syndrome). Ten genes have now been identified for microcephalic primordial dwarfism, encoding proteins involved in fundamental cellular processes including genome replication (ORC1 [origin recognition complex 1], ORC4, ORC6, CDT1, and CDC6), DNA damage response (ATR [ataxia-telangiectasia and Rad3-related]), mRNA splicing (U4atac), and centrosome function (CEP152, PCNT, and CPAP). Here, we review the cellular and developmental mechanisms underlying the pathogenesis of these conditions and address whether further study of these genes could provide novel insight into the physiological regulation of organism growth. PMID- 21979916 TI - Essential role for DNA-PK-mediated phosphorylation of NR4A nuclear orphan receptors in DNA double-strand break repair. AB - DNA-dependent protein kinase (DNA-PK) is a central regulator of DNA double-strand break (DSB) repair; however, the identity of relevant DNA-PK substrates has remained elusive. NR4A nuclear orphan receptors function as sequence-specific DNA binding transcription factors that participate in adaptive and stress-related cell responses. We show here that NR4A proteins interact with the DNA-PK catalytic subunit and, upon exposure to DNA damage, translocate to DSB foci by a mechanism requiring the activity of poly(ADP-ribose) polymerase-1 (PARP-1). At DNA repair foci, NR4A is phosphorylated by DNA-PK and promotes DSB repair. Notably, NR4A transcriptional activity is entirely dispensable in this function, and core components of the DNA repair machinery are not transcriptionally regulated by NR4A. Instead, NR4A functions directly at DNA repair sites by a process that requires phosphorylation by DNA-PK. Furthermore, a severe combined immunodeficiency (SCID)-causing mutation in the human gene encoding the DNA-PK catalytic subunit impairs the interaction and phosphorylation of NR4A at DSBs. Thus, NR4As represent an entirely novel component of DNA damage response and are substrates of DNA-PK in the process of DSB repair. PMID- 21979917 TI - R-loop-mediated genomic instability is caused by impairment of replication fork progression. AB - Transcriptional R loops are anomalous RNA:DNA hybrids that have been detected in organisms from bacteria to humans. These structures have been shown in eukaryotes to result in DNA damage and rearrangements; however, the mechanisms underlying these effects have remained largely unknown. To investigate this, we first show that R-loop formation induces chromosomal DNA rearrangements and recombination in Escherichia coli, just as it does in eukaryotes. More importantly, we then show that R-loop formation causes DNA replication fork stalling, and that this in fact underlies the effects of R loops on genomic stability. Strikingly, we found that attenuation of replication strongly suppresses R-loop-mediated DNA rearrangements in both E. coli and HeLa cells. Our findings thus provide a direct demonstration that R-loop formation impairs DNA replication and that this is responsible for the deleterious effects of R loops on genome stability from bacteria to humans. PMID- 21979918 TI - Translational coregulation of 5'TOP mRNAs by TIA-1 and TIAR. AB - The response of cells to changes in their environment often requires coregulation of gene networks, but little is known about how this can occur at the post transcriptional level. An important example of post-transcriptional coregulation is the selective translational regulation in response to growth conditions of mammalian mRNAs that encode protein biosynthesis factors and contain hallmark 5' terminal oligopyrimidine tracts (5'TOP). However, the responsible trans-factors and the mechanism by which they coregulate 5'TOP mRNAs have remained elusive. Here we identify stress granule-associated TIA-1 and TIAR proteins as key factors in human 5'TOP mRNA regulation, which upon amino acid starvation assemble onto the 5' end of 5'TOP mRNAs and arrest translation at the initiation step, as evidenced by TIA-1/TIAR-dependent 5'TOP mRNA translation repression, polysome release, and accumulation in stress granules. This requires starvation-mediated activation of the GCN2 (general control nonderepressible 2) kinase and inactivation of the mTOR (mammalian target of rapamycin) signaling pathway. Our findings provide a mechanistic explanation to the long-standing question of how the network of 5'TOP mRNAs are coregulated according to amino acid availability, thereby allowing redirection of limited resources to mount a nutrient deprivation response. This presents a fundamental example of how a group of mRNAs can be translationally coregulated in response to changes in the cellular environment. PMID- 21979919 TI - TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway. AB - The biological response to tumor necrosis factor (TNF) involves activation of MAP kinases. Here we report a mechanism of MAP kinase activation by TNF that is mediated by the Rho GTPase family members Rac/Cdc42. This signaling pathway requires Src-dependent activation of the guanosine nucleotide exchange factor Vav, activation of Rac/Cdc42, and the engagement of the Rac/Cdc42 interaction site (CRIB motif) on mixed-lineage protein kinases (MLKs). We show that this pathway is essential for full MAP kinase activation during the response to TNF. Moreover, this MLK pathway contributes to inflammation in vivo. PMID- 21979922 TI - Endoscopic injection of autologous blood for bleeding gastroduodenal ulcers. AB - Endoscopic injection of diluted epinephrine and the application of endoclips or thermal probes are established endoscopic therapies for peptic ulcer bleeding (PUB). However, autologous blood may offer advantages at least over diluted epinephrine due to its specific properties: corpuscular components may provide prolonged persistence and procoagulatory constituents may additionally prevent recurrent bleeding. We performed successful endoscopic injection of autologous blood for acute spurting (Forrest Ia) or oozing (Ib) bleeding from duodenal or gastric ulcers. The injection of autologous blood was simple to apply and achieved hemostasis in bleeding Forrest I peptic ulcers. This technique can be considered as an adjunct or an alternative to other methods for endoscopic control of PUB. PMID- 21979920 TI - The Caenorhabditis elegans SOMI-1 zinc finger protein and SWI/SNF promote regulation of development by the mir-84 microRNA. AB - Hundreds of microRNAs (miRNAs) have been discovered in metazoans and plants, and understanding of their biogenesis has advanced dramatically; however, relatively little is known about the cofactors necessary for miRNA regulation of target gene expression. In Caenorhabditis elegans, the conserved miRNA let-7 and its paralogs, including mir-84, control the timing of stage-specific developmental events. To identify factors required for the activity of mir-84 and possibly other miRNAs, we screened for mutations that suppress the developmental defects caused by overexpression of mir-84. Mutations in the somi-1 gene prevent these defects without affecting the expression level of mir-84. Loss of somi-1 also causes phenotypes similar to deletion of mir-84, showing that somi-1 is necessary for the normal function of this miRNA. somi-1 encodes a zinc finger protein that localizes to nuclear foci and binds the promoters of let-60/RAS, lin-14, and lin 28, genes that may be targeted by mir-84 and similar miRNAs. Genetic evidence shows that somi-1 inhibits lin-14 and induction of the vulval precursors by the let-60/RAS pathway. Proteomic and genetic screens identified conserved chromatin remodeling and homeodomain transcription factor complexes that work with somi-1 to regulate differentiation. Our results suggest that somi-1 coordinates a nuclear response that complements the activity of mir-84. PMID- 21979921 TI - Cooperation of Escherichia coli Hfq hexamers in DsrA binding. AB - Hfq is a bacterial post-transcriptional regulator. It facilitates base-pairing between sRNA and target mRNA. Hfq mediates DsrA-dependent translational activation of rpoS mRNA at low temperatures. rpoS encodes the stationary-phase sigma factor sigma(S), which is the central regulator in general stress response. However, structural information on Hfq-DsrA interaction is not yet available. Although Hfq is reported to hydrolyze ATP, the ATP-binding site is still unknown. Here, we report a ternary crystal complex structure of Escherichia coli Hfq bound to a major Hfq recognition region on DsrA (AU(6)A) together with ADP, and a crystal complex structure of Hfq bound to ADP. AU(6)A binds to the proximal and distal sides of two Hfq hexamers. ADP binds to a purine-selective site on the distal side and contacts conserved arginine or glutamine residues on the proximal side of another hexamer. This binding mode is different from previously postulated. The cooperation of two different Hfq hexamers upon nucleic acid binding in solution is verified by fluorescence polarization and solution nuclear magnetic resonance (NMR) experiments using fragments of Hfq and DsrA. Fluorescence resonance energy transfer conducted with full-length Hfq and DsrA also supports cooperation of Hfq hexamers upon DsrA binding. The implications of Hfq hexamer cooperation have been discussed. PMID- 21979923 TI - Augmentative effects of fluvoxamine on duloxetine plasma levels in depressed patients. AB - Duloxetine is a potent and selective inhibitor of serotonin and norepinephrine reuptake with weak activity on dopamine reuptake. Enzymes involved in duloxetine metabolism are cytochrome P450 isoenzymes (CYP) CYP1A2 and to a lesser extent CYP2D6 whereas the selective serotonin reuptake inhibitor Fluvoxamine is known to be a potent inhibitor of CYP1A2. Changes in plasma levels of duloxetine revealing pharmacokinetic interactions with fluvoxamine, clinical effects and adverse effects of adding fluvoxamine in thirteen patients with a steady-state duloxetine treatment by intraindividual comparisons were analyzed in this retrospective survey. Patients had been treated with duloxetine under steady-state conditions until fluvoxamine was added. Plasma duloxetine levels were measured at steady state of different daily doses due to lacking experience with the combination of DLX and FLX. Adding 25 mg of fluvoxamine (FLX) per day to a steady-state treatment with 30 mg of duloxetine (DLX) in 8 patients led to an average increase of duloxetine plasma levels that was 3-fold with a magnitude of 50-506%. Our findings indicate that duloxetine plasma levels can be enhanced by a potent CYP1A2 inhibition by FLX and that DLX, even in higher plasma levels, seems to be well tolerated. The use of combined treatments, however, underscores the importance of understanding pharmacokinetic interactions. PMID- 21979924 TI - Partial status epilepticus after electroconvulsive therapy and medical treatment with bupropion. AB - Electroconvulsive therapy (ECT) is the most effective treatment for therapy refractory depression. Usually, prior antidepressant medication will be continued during ECT. However, the seizure threshold may be influenced by psychotropic drugs. We report a patient who received right unilateral ECT under concomitant treatment with bupropion, a selective noradrenaline- and dopamine-reuptake inhibitor. After the fourth session, a focal status epilepticus occurred, which was pharmacoresistant for the duration of 12 days. We assume that the induction of a status may be facilitated by a lowering of the seizure threshold due to bupropion. An evaluation of drug therapy and control of EEG before and during ECT are recommended, especially when the drug treatment has an influence on the seizure threshold. PMID- 21979925 TI - Exploratory review of placebo characteristics reported in randomised placebo controlled antidepressant drug trials. AB - INTRODUCTION: Systematic reviews of randomised placebo controlled trials of antidepressants have found small and decreasing differences in outcome between pharmacological and placebo arms. Increased knowledge of placebo characteristics may provide greater understanding of antidepressant pharmacological effect. We conducted a systematic review to identify the presence of key placebo characteristics in a sample of antidepressant clinical trials. METHODS: 82 randomised placebo controlled trials of antidepressants, selected in 2 previous systematic reviews (Walsh et al. 2002; NICE 2009), were examined. Presence of placebo characteristics documented using detailed standardised form, with 5 domains: health care environment, practitioner characteristics, patient characteristics, practitioner-patient interaction, and non-pharmaceutical drug characteristics. First authors contacted where possible, and further clarification sought on placebo characteristics within trials. RESULTS: Percentage of trials reporting placebo characteristics within the 5 domains: health care setting 100%, environment 5%; practitioner profession 18%, status 0%, incentives 0%, gender 10%, age 4%, beliefs 6%; patient age 85%, gender 91%, ethnicity 41%, diagnosis and severity 100%, recruitment 16%, incentives 12%, co morbidity 12%, expectation 0%, beliefs 0%; patient-practitioner interaction type of care 10%, number of visits 94%, empathy and congruence 2%; drug form 45% and frequency 57%. DISCUSSION: Placebo characteristics represent confounding variables which, if not adequately controlled for, could distort findings and conclusions about efficacy. The lack of systematic recording of many placebo characteristics in antidepressant drug trials is a cause for concern. To reduce imprecision and increase generalisability, future antidepressant clinical trials should consider the impact of key placebo characteristics and record their presence when disseminating findings. PMID- 21979926 TI - Agomelatine improves sleep in a patient with fatal familial insomnia. AB - A young patient with FFI was started on agomelatine 25 mg to medicate nocturnal insomnia. Under this treatment sleep efficiency was improved, slow wave sleep was high and awakenings during sleep period time were far less than before. Clinically the patient was less restless during nighttime. PMID- 21979927 TI - Identifying context-specific competencies required by community Australian Football sports trainers. AB - BACKGROUND: First-aid is a recommended injury prevention and risk management strategy in community sport; however, little is known about the sport-specific competencies required by first-aid providers. OBJECTIVE: To achieve expert consensus on the competencies required by community Australian Football (community-AF) sports trainers. STUDY DESIGN: A three-round online Delphi process. SETTING: Community-AF. PARTICIPANTS: 16 Australian sports first-aid and community-AF experts. OUTCOME MEASURES: Rating of competencies as either 'essential', 'expected', 'ideal' or 'not required'. Results After Round 3, 47 of the 77 (61%) competencies were endorsed as 'essential' or 'expected' for a sports trainer to effectively perform the activities required to the standards expected at a community-AF club by >=75% of experts. These competencies covered: the role of the sports trainer; the responsibilities of the sports trainer; emergency management; injury and illness assessment and immediate management; taping; and injury prevention and risk management. Four competencies (5%) were endorsed as 'ideal' or 'not required' by >=85% of experts and were excluded from further consideration. The 26 competencies where consensus was not reached were retained as second-tier, optional competencies. CONCLUSIONS: Sports trainers are important members of on-field first-aid teams, providing support to both injured players and other sports medicine professionals. The competencies identified in this study provide the basis of a proposed two-tiered community-AF-specific sports trainer education structure that can be implemented by the peak sports body. This includes six mandatory modules, relating to the 'required' competencies, and a further six optional modules covering competencies on which consensus was not reached. PMID- 21979928 TI - Absolute quantification and differential expression of drug transporters, cytochrome P450 enzymes, and UDP-glucuronosyltransferases in cultured primary human hepatocytes. AB - The levels of metabolizing enzymes and transporters expressed in hepatocytes are decisive factors for hepatobiliary disposition of most drugs. Induction via nuclear receptor activation can significantly alter those levels, with the coregulation of multiple enzymes and transporters occurring to different extents. Here, we report the use of a targeted liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) method for concurrent quantification of multiple cytochrome P450 (P450), UDP-glucuronosyltransferase (UGT), and transporter proteins in cultured primary human hepatocytes. The effects of culture format (i.e., sandwich culture versus conventional culture) and of dexamethasone (DEX) media concentrations on mRNA, protein, and activity levels were determined for three donors, and protein expression was compared with that in liver. In general, P450 and UGT expression was lower in hepatocyte cultures than that in liver, and CYP2C9 was found to be the most abundant P450 isoform expressed in cultured hepatocytes. The sandwich culture format and 0.1 MUM DEX in media retained the protein expression in the hepatocytes closest to the levels found in liver. However, higher in vitro expression was observed for drug transporters, especially for multidrug resistance protein 1 and breast cancer resistance protein. Direct protein quantification was applied successfully to study in vitro induction in sandwich cultured primary hepatocytes in a 24-well format using the prototypical inducers rifampicin, omeprazole, and phenobarbital. We conclude that targeted absolute LC-MS/MS quantification of drug-metabolizing enzymes and transporters can broaden the scope and significantly increase the impact of in vitro drug metabolism studies, such as induction, as an important supplement or future alternative to mRNA and activity data. PMID- 21979929 TI - Antiplasmodial quinones from Pentas longiflora and Pentas lanceolata. AB - The dichloromethane/methanol (1:1) extracts of the roots of Pentas longiflora and Pentas lanceolata showed low micromolar (IC(50) = 0.9-3 ug/mL) IN VITRO antiplasmodial activity against chloroquine-resistant (W2) and chloroquine sensitive (D6) strains of PLASMODIUM FALCIPARUM. Chromatographic separation of the extract of PENTAS LONGIFLORA led to the isolation of the pyranonaphthoquinones pentalongin (1) and psychorubrin (2) with IC(50) values below 1 ug/mL and the naphthalene derivative mollugin (3), which showed marginal activity. Similar treatment of Pentas lanceolata led to the isolation of eight anthraquinones ( 4-11, IC(50) = 5-31 ug/mL) of which one is new (5,6 dihydroxydamnacanthol, 11), while three--nordamnacanthal (7), lucidin-omega methyl ether (9), and damnacanthol (10)--are reported here for the first time from the genus Pentas. The compounds were identified by NMR and mass spectroscopic techniques. PMID- 21979930 TI - Antifungal sesquiterpenes from Cedrus deodara. AB - Two new sesquiterpenes, (E)-(2S,3S,6R)-atlantone-2,3-diol (1) and (E)-(2S,3S,6S) atlantone-2,3,6-triol (2), along with two known sesquiterpenes, atlantolone (3) and (E)-alpha-atlantone (4), were isolated from Cedrus deodara Loud. The structures of the new compounds were elucidated on the basis of UV, IR, NMR, HR ESI-QTOF-MS, and EI mass spectral studies. The n-hexane and chloroformextracts of sawdust and compounds 3 and 4 from the plant exhibited antifungal activity against Aspergillus flavus, A. niger, A. ochracoeus, A. parasiticus, and A. sydowii. A weak activity was also recorded against A. parasiticus and A. sydowii for compound 1, while Trichophyton rubrum was inhibited by compound 2 and the extracts. PMID- 21979931 TI - Constituents with DNA topoisomerases I and II inhibitory activity and cytotoxicity from the roots of Rubia cordifolia. AB - Activity-directed isolation of the ethyl acetate fraction from the roots of Rubia cordifolia resulted in the identification of a new anthraquinone, 1,3,6 trihydroxy-2-hydroxymethyl-9,10-anthraquinone-3- O- alpha- L-rhamnopyranosyl-(1 > 2)- beta-D-(6'-O-acetyl)-glucopyranoside (1), two new dihydronaphtoquinones, 1,4-dihydroxy-2-carbomethoxy-3-prenylnaphthalene-1-O- beta-D-glucopyranoside (2) and mollugin-1-O- beta- D-glucopyranoside (3), and a new monoterpenoid, 3 R,3a S,4 R,6a R-3,4,6-tris(hydroxymethyl)-3,3a,4,6a-tetrahydro-2 H-cyclopenta[ B]furan 2-one (4), together with nine known compounds (5-13). The structures of these compounds were elucidated on the basis of spectroscopic evidence. In addition, their DNA topoisomerases I and II inhibitory activity and cytotoxicity were measured. PMID- 21979932 TI - No evidence of elevated germline mutation accumulation under oxidative stress in Caenorhabditis elegans. AB - Variation in rates of molecular evolution has been attributed to numerous, interrelated causes, including metabolic rate, body size, and generation time. Speculation concerning the influence of metabolic rate on rates of evolution often invokes the putative mutagenic effects of oxidative stress. To isolate the effects of oxidative stress on the germline from the effects of metabolic rate, generation time, and other factors, we allowed mutations to accumulate under relaxed selection for 125 generations in two strains of the nematode Caenorhabditis elegans, the canonical wild-type strain (N2) and a mutant strain with elevated steady-state oxidative stress (mev-1). Contrary to our expectation, the mutational decline in fitness did not differ between N2 and mev-1. This result suggests that the mutagenic effects of oxidative stress in C. elegans are minor relative to the effects of other types of mutations, such as errors during DNA replication. However, mev-1 MA lines did go extinct more frequently than wild type lines; some possible explanations for the difference in extinction rate are discussed. PMID- 21979933 TI - Lithospheric thinning beneath rifted regions of Southern California. AB - The stretching and break-up of tectonic plates by rifting control the evolution of continents and oceans, but the processes by which lithosphere deforms and accommodates strain during rifting remain enigmatic. Using scattering of teleseismic shear waves beneath rifted zones and adjacent areas in Southern California, we resolve the lithosphere-asthenosphere boundary and lithospheric thickness variations to directly constrain this deformation. Substantial and laterally abrupt lithospheric thinning beneath rifted regions suggests efficient strain localization. In the Salton Trough, either the mantle lithosphere has experienced more thinning than the crust, or large volumes of new lithosphere have been created. Lack of a systematic offset between surface and deep lithospheric deformation rules out simple shear along throughgoing unidirectional shallow-dipping shear zones, but is consistent with symmetric extension of the lithosphere. PMID- 21979935 TI - Hot carrier-assisted intrinsic photoresponse in graphene. AB - We report on the intrinsic optoelectronic response of high-quality dual-gated monolayer and bilayer graphene p-n junction devices. Local laser excitation (of wavelength 850 nanometers) at the p-n interface leads to striking six-fold photovoltage patterns as a function of bottom- and top-gate voltages. These patterns, together with the measured spatial and density dependence of the photoresponse, provide strong evidence that nonlocal hot carrier transport, rather than the photovoltaic effect, dominates the intrinsic photoresponse in graphene. This regime, which features a long-lived and spatially distributed hot carrier population, may offer a path to hot carrier-assisted thermoelectric technologies for efficient solar energy harvesting. PMID- 21979934 TI - An activating mutation of AKT2 and human hypoglycemia. AB - Pathological fasting hypoglycemia in humans is usually explained by excessive circulating insulin or insulin-like molecules or by inborn errors of metabolism impairing liver glucose production. We studied three unrelated children with unexplained, recurrent, and severe fasting hypoglycemia and asymmetrical growth. All were found to carry the same de novo mutation, p.Glu17Lys, in the serine/threonine kinase AKT2, in two cases as heterozygotes and in one case in mosaic form. In heterologous cells, the mutant AKT2 was constitutively recruited to the plasma membrane, leading to insulin-independent activation of downstream signaling. Thus, systemic metabolic disease can result from constitutive, cell autonomous activation of signaling pathways normally controlled by insulin. PMID- 21979937 TI - The influence of Late Quaternary climate-change velocity on species endemism. AB - The effects of climate change on biodiversity should depend in part on climate displacement rate (climate-change velocity) and its interaction with species' capacity to migrate. We estimated Late Quaternary glacial-interglacial climate change velocity by integrating macroclimatic shifts since the Last Glacial Maximum with topoclimatic gradients. Globally, areas with high velocities were associated with marked absences of small-ranged amphibians, mammals, and birds. The association between endemism and velocity was weakest in the highly vagile birds and strongest in the weakly dispersing amphibians, linking dispersal ability to extinction risk due to climate change. High velocity was also associated with low endemism at regional scales, especially in wet and aseasonal regions. Overall, we show that low-velocity areas are essential refuges for Earth's many small-ranged species. PMID- 21979936 TI - Stochastic pulse regulation in bacterial stress response. AB - Gene regulatory circuits can use dynamic, and even stochastic, strategies to respond to environmental conditions. We examined activation of the general stress response mediated by the alternative sigma factor, sigma(B), in individual Bacillus subtilis cells. We observed that energy stress activates sigma(B) in discrete stochastic pulses, with increasing levels of stress leading to higher pulse frequencies. By perturbing and rewiring the endogenous system, we found that this behavior results from three key features of the sigma(B) circuit: an ultrasensitive phosphorylation switch; stochasticity ("noise"), which activates that switch; and a mixed (positive and negative) transcriptional feedback, which can both amplify a pulse and switch it off. Together, these results show how prokaryotes encode signals using stochastic pulse frequency modulation through a compact regulatory architecture. PMID- 21979938 TI - Health and network centrality in a continuing care retirement community. AB - BACKGROUND: The overlap between social networks and health represents a key area of research in social gerontology. Set in a continuing care retirement community, this research focuses on how health is related to outgoing and incoming reports of social interaction among residents. METHOD: Study participants (n = 123) were given the RAND 36-item Health Survey and asked about their social interaction with other people living at the retirement community. Negative binomial and linear regression analysis was used to assess associations between measures of network centrality and health. RESULTS: Retirement community residents in better health received more nominations from their peers about general socializing, net of how many ties they themselves reported. The ties received by healthier people, moreover, tended to come from others who were central in the network. Conversely, those in better health reported fewer close ties with their coresidents, net of the alter reports. DISCUSSION: Results are interpreted in light of status processes, which emerge in bounded social settings. PMID- 21979940 TI - Notch signaling in acute lymphoblastic leukemia: any role for stromal microenvironment? AB - Notch signaling pathway regulates many different events of embryonic and adult development; among them, Notch plays an essential role in the onset of hematopoietic stem cells and influences multiple maturation steps of developing lymphoid and myeloid cells. Deregulation of Notch signaling determines several human disorders, including cancer. In the last decade it became evident that Notch signaling plays pivotal roles in the onset and development of T- and B-cell acute lymphoblastic leukemia by regulating the intracellular molecular pathways involved in leukemia cell survival and proliferation. On the other hand, bone marrow stromal cells are equally necessary for leukemia cell survival by preventing blast cell apoptosis and favoring their reciprocal interactions and cross-talk with bone marrow microenvironment. Quite surprisingly, the link between Notch signaling pathway and bone marrow stromal cells in acute lymphoblastic leukemia has been pointed out only recently. In fact, bone marrow stromal cells express Notch receptors and ligands, through which they can interact with and influence normal and leukemia T- and B-cell survival. Here, the data concerning the development of T- and B-cell acute lymphoblastic leukemia has been critically reviewed in light of the most recent findings on Notch signaling in stromal microenvironment. PMID- 21979939 TI - Regenerating islet-derived 3-alpha is a biomarker of gastrointestinal graft versus-host disease. AB - There are no plasma biomarkers specific for GVHD of the gastrointestinal (GI) tract, the GVHD target organ most associated with nonrelapse mortality (NRM) following hematopoietic cell transplantation (HCT). Using an unbiased, large scale, quantitative proteomic discovery approach to identify candidate biomarkers that were increased in plasma from HCT patients with GI GVHD, 74 proteins were increased at least 2-fold; 5 were of GI origin. We validated the lead candidate, REG3alpha, by ELISA in samples from 1014 HCT patients from 3 transplantation centers. Plasma REG3alpha concentrations were 3-fold higher in patients at GI GVHD onset than in all other patients and correlated most closely with lower GI GVHD. REG3alpha concentrations at GVHD onset predicted response to therapy at 4 weeks, 1-year NRM, and 1-year survival (P <= .001). In a multivariate analysis, advanced clinical stage, severe histologic damage, and high REG3alpha concentrations at GVHD diagnosis independently predicted 1-year NRM, which progressively increased with higher numbers of onset risk factors present: 25% for patients with 0 risk factors to 86% with 3 risk factors present (P < .001). REG3alpha is a plasma biomarker of GI GVHD that can be combined with clinical stage and histologic grade to improve risk stratification of patients. PMID- 21979941 TI - D6 facilitates cellular migration and fluid flow to lymph nodes by suppressing lymphatic congestion. AB - Lymphatic endothelial cells are important for efficient flow of antigen-bearing fluid and antigen-presenting cells (APCs) from peripheral sites to lymph nodes (LNs). APC movement to LNs is dependent on the constitutive chemokine receptor CCR7, although how conflicting inflammatory and constitutive chemokine cues are integrated at lymphatic surfaces during this process is not understood. Here we reveal a previously unrecognized aspect of the regulation of this process. The D6 chemokine-scavenging receptor, which is expressed on lymphatic endothelial cells (LECs), maintains lymphatic surfaces free of inflammatory CC-chemokines and minimizes interaction of inflammatory leukocytes with these surfaces. D6 does not alter the level of CCR7 ligands on LECs, thus ensuring selective presentation of homeostatic chemokines for interaction with CCR7(+) APCs. Accordingly, in D6 deficient mice, inflammatory CC-chemokine adherence to LECs results in inappropriate perilymphatic accumulation of inflammatory leukocytes at peripheral inflamed sites and draining LNs. This results in lymphatic congestion and impaired movement of APCs, and fluid, from inflamed sites to LNs. We propose that D6, by suppressing inflammatory chemokine binding to lymphatic surfaces, and thereby preventing inappropriate inflammatory leukocyte adherence, is a key regulator of lymphatic function and a novel, and indispensable, contributor to the integration of innate and adaptive immune responses. PMID- 21979943 TI - Modeling tumor invasion and metastasis in Drosophila. AB - Conservation of major signaling pathways between humans and flies has made Drosophila a useful model organism for cancer research. Our understanding of the mechanisms regulating cell growth, differentiation and development has been considerably advanced by studies in Drosophila. Several recent high profile studies have examined the processes constraining the metastatic growth of tumor cells in fruit fly models. Cell invasion can be studied in the context of an in vivo setting in flies, enabling the genetic requirements of the microenvironment of tumor cells undergoing metastasis to be analyzed. This Perspective discusses the strengths and limitations of Drosophila models of cancer invasion and the unique tools that have enabled these studies. It also highlights several recent reports that together make a strong case for Drosophila as a system with the potential for both testing novel concepts in tumor progression and cell invasion, and for uncovering players in metastasis. PMID- 21979942 TI - Deconstructing host-pathogen interactions in Drosophila. AB - Many of the cellular mechanisms underlying host responses to pathogens have been well conserved during evolution. As a result, Drosophila can be used to deconstruct many of the key events in host-pathogen interactions by using a wealth of well-developed molecular and genetic tools. In this review, we aim to emphasize the great leverage provided by the suite of genomic and classical genetic approaches available in flies for decoding details of host-pathogen interactions; these findings can then be applied to studies in higher organisms. We first briefly summarize the general strategies by which Drosophila resists and responds to pathogens. We then focus on how recently developed genome-wide RNA interference (RNAi) screens conducted in cells and flies, combined with classical genetic methods, have provided molecular insight into host-pathogen interactions, covering examples of bacteria, fungi and viruses. Finally, we discuss novel strategies for how flies can be used as a tool to examine how specific isolated virulence factors act on an intact host. PMID- 21979945 TI - Home oxygen - spend to save? PMID- 21979944 TI - A zebrafish transgenic model of Ewing's sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis. AB - Ewing's sarcoma, a malignant bone tumor of children and young adults, is a member of the small-round-blue-cell tumor family. Ewing's sarcoma family tumors (ESFTs), which include peripheral primitive neuroectodermal tumors (PNETs), are characterized by chromosomal translocations that generate fusions between the EWS gene and ETS-family transcription factors, most commonly FLI1. The EWS-FLI1 fusion oncoprotein represents an attractive therapeutic target for treatment of Ewing's sarcoma. The cell of origin of ESFT and the molecular mechanisms by which EWS-FLI1 mediates tumorigenesis remain unknown, and few animal models of Ewing's sarcoma exist. Here, we report the use of zebrafish as a vertebrate model of EWS FLI1 function and tumorigenesis. Mosaic expression of the human EWS-FLI1 fusion protein in zebrafish caused the development of tumors with histology strongly resembling that of human Ewing's sarcoma. The incidence of tumors increased in a p53 mutant background, suggesting that the p53 pathway suppresses EWS-FLI1-driven tumorigenesis. Gene expression profiling of the zebrafish tumors defined a set of genes that might be regulated by EWS-FLI1, including the zebrafish ortholog of a crucial EWS-FLI1 target gene in humans. Stable zebrafish transgenic lines expressing EWS-FLI1 under the control of the heat-shock promoter exhibit altered embryonic development and defective convergence and extension, suggesting that EWS-FLI1 interacts with conserved developmental pathways. These results indicate that functional targets of EWS-FLI1 that mediate tumorigenesis are conserved from zebrafish to human and provide a novel context in which to study the function of this fusion oncogene. PMID- 21979946 TI - Germline SDHx variants modify breast and thyroid cancer risks in Cowden and Cowden-like syndrome via FAD/NAD-dependant destabilization of p53. AB - Cowden syndrome (CS), a Mendelian autosomal-dominant disorder, predisposes to breast, thyroid and other cancers. Germline mutations in phosphatase and tensin homolog (PTEN) have been recently reported in 23% of a large series of classic CS. Here, we validated our small (n = 10) pilot study in a large patient series that germline variations in succinate dehydrogenase genes (SDHx) occur in 8% (49/608) of PTEN mutation-negative CS and CS-like (CSL) individuals (SDH(var+)). None of these SDHx variants was found in 700 population controls (P < 0.0001). We then found that SDHx variants also occur in 6% (26/444) of PTEN mutation-positive (PTEN(mut+)) CS/CSL individuals (PTEN(mut+)/SDH(var+)). Of 22 PTEN(mut+)/SDH(var+) females, 17 had breast cancers compared with 34/105 PTEN(mut+) (P < 0.001) or 27/47 SDH(var+) patients (P = 0.06). Notably, individuals with SDH(var+) alone had the highest thyroid cancer prevalence (24/47) compared with PTEN(mut+) patients (27/105, P = 0.002) or PTEN(mut+)/SDH(var+) carriers (6/22, P = 0.038). Patient-derived SDH(var+) lymphoblastoid cells had elevated cellular reactive oxygen species, highest in PTEN(mut+)/SDH(var+) cells, correlating with apoptosis resistance. SDH(var+) cells showed stabilized and hyperactivated hypoxia inducible factor (HIF)1alpha signaling. Most interestingly, we also observed the loss of steady-state p53 in the majority of SDH(var+) cells. This loss of p53 was regulated by MDM2 independent NADH quinone oxidoreductase 1-mediated protein degradation, likely due to the imbalance of flavin adenine dinucleotide/nicotinamide adenine dinucleotide in SDH(var+) cells. Our data suggest the potential regulation of HIF1alpha, p53 and PTEN signaling by mitochondrial metabolism in CS/CSL tumorigenesis. Together, our findings suggest the importance of considering SDHx as candidate predisposing and modifier genes for CS/CSL-related malignancy risks, and a mechanism which suggests ways of therapeutic reversal or prevention. PMID- 21979947 TI - A genome-wide association study identifies a potential novel gene locus for keratoconus, one of the commonest causes for corneal transplantation in developed countries. AB - Keratoconus is a condition in which the cornea progressively thins over time, and is a major cause for cornea transplantation. To identify keratoconus susceptibility regions, we performed a comprehensive genome-wide association study (GWAS) using a discovery and replication design. A discovery panel of 222 keratoconus Caucasian patients and 3324 Caucasian controls was genotyped using Illumina 370K beadchips. Further associated and fine-mapping single nucleotide polymorphisms (SNPs) (n= 4905) were genotyped in an independent replication case control panel of 304 cases and 518 controls and a family panel of 307 subjects in 70 families. Logistic regression models implemented in PLINK were performed to test associations in case-control samples with and without principal component (PC) adjustments. Generalized estimation equation models accounting for familial correlations implemented in GWAF were used for association testing in families. No genome-wide associations were identified in the discovery GWAS panel. From the initial testing without adjustments for PCs, the top three SNPs located at 3p26 (rs6442925), 2q21.3 (rs4954218) and 19q13.3 (rs1428642) were identified with unadjusted P-values of 6.5 * 10(-8), 2.4 * 10(-7) and 3.1 * 10(-7), respectively. After adjustments for PCs, rs1428642 became the most significant through the genome with a P-value of 1.4 * 10(-6), while rs6442925 and rs4954218 were less significant (P= 1.9 * 10(-5) and 2.6 * 10(-4)). SNP rs4954218 was confirmed in two independent replication panels with P-values of 0.004 and 0.009, respectively. Meta-analysis revealed a highest association at rs4954218 with adjusted P= 1.6 * 10(-7) (unadjusted P= 1.2 * 10(-9)). These findings suggest SNP rs4954218, located near the RAB3GAP1 gene, previously reported to be associated with corneal malformation, is a potential susceptibility locus for keratoconus. PMID- 21979948 TI - Endoplasmic reticulum-associated degradation (ERAD) and free oligosaccharide generation in Saccharomyces cerevisiae. AB - In Saccharomyces cerevisiae, proteins with misfolded lumenal, membrane, and cytoplasmic domains are cleared from the endoplasmic reticulum (ER) by ER associated degradation (ERAD)-L, -M, and -C, respectively. ERAD-L is N-glycan dependent and is characterized by ER mannosidase (Mns1p) and ER mannosidase-like protein (Mnl1p), which generate Man(7)GlcNAc(2) (d1) N-glycans with non-reducing alpha1,6-mannosyl residues. Glycoproteins bearing this motif bind Yos9p and are dislocated into the cytoplasm and then deglycosylated by peptide N-glycanase (Png1p) to yield free oligosaccharides (fOS). Here, we examined yeast fOS metabolism as a function of cell growth in order to obtain quantitative and mechanistic insights into ERAD. We demonstrate that both Png1p-dependent generation of Man(7-10)GlcNAc(2) fOS and vacuolar alpha-mannosidase (Ams1p) dependent fOS demannosylation to yield Man(1)GlcNAc(2) are strikingly up regulated during post-diauxic growth which occurs when the culture medium is depleted of glucose. Gene deletions in the ams1Delta background revealed that, as anticipated, Mns1p and Mnl1p are required for efficient generation of the Man(7)GlcNAc(2) (d1) fOS, but for the first time, we demonstrate that small amounts of this fOS are generated in an Mnl1p-independent, Mns1p-dependent pathway and that a Man(8)GlcNAc(2) fOS that is known to bind Yos9p is generated in an Mnl1p-dependent, Mns1p-independent manner. This latter observation adds mechanistic insight into a recently described Mnl1p-dependent, Mns1p-independent ERAD pathway. Finally, we show that 50% of fOS generation is independent of ERAD L, and because our data indicate that ERAD-M and ERAD-C contribute little to fOS levels, other important processes underlie fOS generation in S. cerevisiae. PMID- 21979949 TI - Oligomerization of DNMT3A controls the mechanism of de novo DNA methylation. AB - DNMT3A is one of two human de novo DNA methyltransferases essential for regulating gene expression through cellular development and differentiation. Here we describe the consequences of single amino acid mutations, including those implicated in the development of acute myeloid leukemia (AML) and myelodysplastic syndromes, at the DNMT3A.DNMT3A homotetramer and DNMT3A.DNMT3L heterotetramer interfaces. A model for the DNMT3A homotetramer was developed via computational interface scanning and tested using light scattering and electrophoretic mobility shift assays. Distinct oligomeric states were functionally characterized using fluorescence anisotropy and steady-state kinetics. Replacement of residues that result in DNMT3A dimers, including those identified in AML patients, show minor changes in methylation activity but lose the capacity for processive catalysis on multisite DNA substrates, unlike the highly processive wild-type enzyme. Our results are consistent with the bimodal distribution of DNA methylation in vivo and the loss of clustered methylation in AML patients. Tetramerization with the known interacting partner DNMT3L rescues processive catalysis, demonstrating that protein binding at the DNMT3A tetramer interface can modulate methylation patterning. Our results provide a structural mechanism for the regulation of DNMT3A activity and epigenetic imprinting. PMID- 21979950 TI - In vivo role for the chromatin-remodeling enzyme SWI/SNF in the removal of promoter nucleosomes by disassembly rather than sliding. AB - Analysis of in vivo chromatin remodeling at the PHO5 promoter of yeast led to the conclusion that remodeling removes nucleosomes from the promoter by disassembly rather than sliding away from the promoter. The catalytic activities required for nucleosome disassembly remain unknown. Transcriptional activation of the yeast PHO8 gene was found to depend on the chromatin-remodeling complex SWI/SNF, whereas activation of PHO5 was not. Here, we show that PHO8 gene circles formed in vivo lose nucleosomes upon PHO8 induction, indicative of nucleosome removal by disassembly. Our quantitative analysis of expression noise and chromatin remodeling data indicates that the dynamics of continual nucleosome removal and reformation at the activated promoters of PHO5 and PHO8 are closely similar. In contrast to PHO5, however, activator-stimulated transcription of PHO8 appears to be limited mostly to the acceleration of promoter nucleosome disassembly with little or no acceleration of promoter transitions following nucleosome disassembly, accounting for the markedly lower expression level of PHO8. PMID- 21979951 TI - Akt2 kinase suppresses glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-mediated apoptosis in ovarian cancer cells via phosphorylating GAPDH at threonine 237 and decreasing its nuclear translocation. AB - Protein kinase B (Akt) plays important roles in regulation of cell growth and survival, but while many aspects of its mechanism of action are known, there are potentially additional regulatory events that remain to be discovered. Here we detected a 36-kDa protein that was co-immunoprecipitated with protein kinase Bbeta (Akt2) in OVCAR-3 ovarian cancer cells. The protein was identified to be glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by MALDI-TOF/TOF MS, and the interaction of Akt2 and GAPDH was verified by reverse immunoprecipitation. Our further study showed that Akt2 may suppress GAPDH-mediated apoptosis in ovarian cancer cells. Overexpression of GAPDH increased ovarian cancer cell apoptosis induced by H(2)O(2), which was inhibited by Akt2 overexpression and restored by the PI3K/Akt inhibitor wortmannin or Akt2 siRNA. Akt2 phosphorylated Thr-237 of GAPDH and decreased its nuclear translocation, an essential step for GAPDH mediated apoptosis. The interaction between Akt2 and GAPDH may be important in ovarian cancer as immunohistochemical analysis of 10 normal and 30 cancerous ovarian tissues revealed that decreased nuclear expression of GAPDH correlated with activation (phosphorylation) of Akt2. In conclusion, our study suggests that activated Akt2 may increase ovarian cancer cell survival via inhibition of GAPDH induced apoptosis. This effect of Akt2 is partly mediated by its phosphorylation of GAPDH at Thr-237, which results in the inhibition of GAPDH nuclear translocation. PMID- 21979952 TI - N-Acetylfarnesylcysteine is a novel class of peroxisome proliferator-activated receptor gamma ligand with partial and full agonist activity in vitro and in vivo. AB - The thiazolidedione (TZD) class of drugs is clinically approved for the treatment of type 2 diabetes. The therapeutic actions of TZDs are mediated via activation of peroxisome proliferator-activated receptor gamma (PPARgamma). Despite their widespread use, concern exists regarding the safety of currently used TZDs. This has prompted the development of selective PPARgamma modulators (SPPARMs), compounds that promote glucose homeostasis but with reduced side effects due to partial PPARgamma agonism. However, this also results in partial agonism with respect to PPARgamma target genes promoting glucose homeostasis. Using a gene expression-based screening approach we identified N-acetylfarnesylcysteine (AFC) as both a full and partial agonist depending on the PPARgamma target gene (differential SPPARM). AFC activated PPARgamma as effectively as rosiglitazone with regard to Adrp, Angptl4, and AdipoQ, but was a partial agonist of aP2, a PPARgamma target gene associated with increased adiposity. Induction of adipogenesis by AFC was also attenuated compared with rosiglitazone. Reporter, ligand binding assays, and dynamic modeling demonstrate that AFC binds and activates PPARgamma in a unique manner compared with other PPARgamma ligands. Importantly, treatment of mice with AFC improved glucose tolerance similar to rosiglitazone, but AFC did not promote weight gain to the same extent. Finally, AFC had effects on adipose tissue remodeling similar to those of rosiglitazone and had enhanced antiinflammatory effects. In conclusion, we describe a new approach for the identification of differential SPPARMs and have identified AFC as a novel class of PPARgamma ligand with both full and partial agonist activity in vitro and in vivo. PMID- 21979953 TI - Bispecific designed ankyrin repeat proteins (DARPins) targeting epidermal growth factor receptor inhibit A431 cell proliferation and receptor recycling. AB - The EGF receptor (EGFR) has been implicated in the development and progression of many tumors. Although monoclonal antibodies directed against EGFR have been approved for the treatment of cancer in combination with chemotherapy, there are limitations in their clinical efficacy, necessitating the search for robust targeting molecules that can be equipped with new effector functions or show a new mechanism of action. Designed ankyrin repeat proteins (DARPins) may provide the targeting component for such novel reagents. Previously, four DARPins were selected against EGFR with (sub)nanomolar affinity. As any targeting module should preferably be able to inhibit EGFR-mediated signaling, their effect on A431 cells overexpressing EGFR was examined: three of them were shown to inhibit proliferation by inducing G(1) arrest, as seen for the Food and Drug Administration-approved antibody cetuximab. To understand this inhibitory mechanism, we mapped the epitopes of the DARPins using yeast surface display. The epitopes for the biologically active DARPins overlapped with the EGF-binding site, whereas the fourth DARPin bound to a different domain, explaining the lack of a biological effect. To optimize the biological activity of the DARPins, we combined two DARPins binding to different epitopes with a flexible linker or with a leucine zipper, leading to a homodimer. The latter DARPin was able to reduce surface EGFR by inhibiting receptor recycling, leading to a dramatic decrease in cell viability. These results indicate that multispecific EGFR-specific DARPins are superior to cetuximab and may form the basis of new opportunities in tumor targeting and tumor therapy. PMID- 21979954 TI - Ligand specificity determined by differentially arranged common ligand-binding residues in bacterial amino acid chemoreceptors Tsr and Tar. AB - Escherichia coli has closely related amino acid chemoreceptors with distinct ligand specificity, Tar for l-aspartate and Tsr for l-serine. Crystallography of the ligand-binding domain of Tar identified the residues interacting with aspartate, most of which are conserved in Tsr. However, swapping of the nonconserved residues between Tsr and Tar did not change ligand specificity. Analyses with chimeric receptors led us to hypothesize that distinct three dimensional arrangements of the conserved ligand-binding residues are responsible for ligand specificity. To test this hypothesis, the structures of the apo- and serine-binding forms of the ligand-binding domain of Tsr were determined at 1.95 and 2.5 A resolutions, respectively. Some of the Tsr residues are arranged differently from the corresponding aspartate-binding residues of Tar to form a high affinity serine-binding pocket. The ligand-binding pocket of Tsr was surrounded by negatively charged residues, which presumably exclude negatively charged aspartate molecules. We propose that all these Tsr- and Tar-specific features contribute to specific recognition of serine and aspartate with the arrangement of the side chain of residue 68 (Asn in Tsr and Ser in Tar) being the most critical. PMID- 21979955 TI - Discovery of a linear cyclotide from the bracelet subfamily and its disulfide mapping by top-down mass spectrometry. AB - Cyclotides are heat-stable macrocyclic peptides from plants that display a wide range of biological activities. They can be divided into two subfamilies: Mobius or bracelet, based on the presence or absence of a cis-proline residue in loop 5, respectively. Currently, over 150 cyclotides have been discovered, but only four linear variants of the Mobius subfamily have been hitherto isolated. In this study, we report the discovery of two novel cyclotides, hedyotide B1 and hedyotide B2, from the aerial parts of Hedyotis biflora. Hedyotide B1 has a cyclic cystine knot structure typical of cyclotides. Interestingly, hedyotide B2 possesses a linear backbone and is the first linear representative of the bracelet subfamily. Disulfide mapping of hedyotide B2 by a top-down MS/MS approach showed that it shares the same knotted disulfide arrangement as conventional cyclotides. Its unfolding pathway also showed that the penetrating disulfide bond Cys III-VI is the most stable disulfide linkage. Cloning of the gene encoding hedyotide B2 revealed a nonsense mutation that introduces a premature stop codon at the conserved Asn residue position, which is essential for an end-to-end backbone ligation. Biophysical characterization showed that hedyotide B2 was more susceptible to exopeptidase degradation as compared with hedyotide B1. Hedyotide B2 was also inactive against all four tested bacterial strains, whereas hedyotide B1 was bactericidal to Escherichia coli and Streptococcus salivarius at low micromolar concentration. Our results provide a deeper understanding of the structures, functions, and biosynthetic processing of cyclotides and uncyclotides in plants. PMID- 21979957 TI - Kinetically controlled drug resistance: how Penicillium brevicompactum survives mycophenolic acid. AB - The filamentous fungus Penicillium brevicompactum produces the immunosuppressive drug mycophenolic acid (MPA), which is a potent inhibitor of eukaryotic IMP dehydrogenases (IMPDHs). IMPDH catalyzes the conversion of IMP to XMP via a covalent enzyme intermediate, E-XMP*; MPA inhibits by trapping E-XMP*. P. brevicompactum (Pb) contains two MPA-resistant IMPDHs, PbIMPDH-A and PbIMPDH-B, which are 17- and 10(3)-fold more resistant to MPA than typically observed. Surprisingly, the active sites of these resistant enzymes are essentially identical to those of MPA-sensitive enzymes, so the mechanistic basis of resistance is not apparent. Here, we show that, unlike MPA-sensitive IMPDHs, formation of E-XMP* is rate-limiting for both PbIMPDH-A and PbIMPDH-B. Therefore, MPA resistance derives from the failure to accumulate the drug-sensitive intermediate. PMID- 21979956 TI - Nucleophosmin interacts with FOXM1 and modulates the level and localization of FOXM1 in human cancer cells. AB - Using mass spectrometric analysis we found that oncogenic transcription factor FOXM1 that is overexpressed in a majority of human cancers interacts with multifunctional protein NPM, which is also overexpressed in a variety of human tumors. Coimmunoprecipitation and glutathione S-transferase pull-down experiments demonstrated that NPM forms a complex with FOXM1 and also identified the regions responsible for their interaction. Immunofluorescence microscopy confirmed the interaction between FOXM1 and NPM in cancer and immortal cells. Furthermore, knockdown of NPM in immortal and cancer cells led to significant down-regulation of FOXM1 similar to its levels in normal cells, suggesting that NPM might modulate FOXM1 level. In addition, in OCI/AML3 leukemia cells where mutant NPM is localized in the cytoplasm we found that typically nuclear FOXM1 was predominantly co-localized with NPM in the cytoplasm, while NPM knockdown led to the disappearance of FOXM1 from the cytoplasm, suggesting that NPM may also determine intracellular localization of FOXM1. Knockdown of FOXM1 or NPM in MIA PaCa-2 pancreatic cancer cells inhibited anchorage-dependent and independent growth in cell culture, and tumor growth in nude mice. In addition, over expression of FOXM1 reversed the effect of NPM knockdown in vitro. Our data suggest that in cancer cells NPM interacts with FOXM1 and their interaction is required for sustaining the level and localization of FOXM1. Targeting the interaction between FOXM1 and NPM by peptides or small molecules may represent a novel therapeutic strategy against cancer. PMID- 21979958 TI - Transcriptional repression of the alpha7 nicotinic acetylcholine receptor subunit gene (CHRNA7) by activating protein-2alpha (AP-2alpha). AB - The CHRNA7 gene, which encodes the alpha7 nicotinic acetylcholine receptor (alpha7*nAChR), has been implicated as a candidate gene in schizophrenia. Expression of the alpha7*nAChR mRNA and protein are reduced in multiple regions of post-mortem brain from patients diagnosed with schizophrenia. Transcriptional regulation may therefore be an important mechanism for the regulation of this gene. A 230-bp proximal promoter fragment, necessary for transcription in cultured neuroblastoma cells, was used to study a putative AP-2alpha binding site. Mutation of the site indicates that AP-2alpha plays a negative role in regulating CHRNA7 transcription. This was confirmed through knockdown and overexpression of AP-2alpha. Electrophoretic mobility shift assays (EMSAs) identified positive DNA-protein interaction at this same site, and supershift assays indicate that the complex includes AP-2alpha. The interaction was confirmed in cells using chromatin immunoprecipitation (ChIP). DNA methylation was discovered as an anomalous mechanism for CHRNA7 regulation in one cell line. These studies suggest a role for AP-2alpha regulation of CHRNA7 mRNA expression in multiple tissues during development. PMID- 21979960 TI - Tailoring and targeting interventions for women with heart disease: the need for gender-based approaches. AB - Implications for practice and research: Increasingly, there is recognition that women with heart disease have greater psychological morbidity than men. Owing to increased rates of depression and other factors, such as older age, women are less likely to adhere to behaviour change strategies and attend cardiac rehabilitation (CR). A tailored and targeted approach, using a gender-based framework and a theoretically derived behaviour change strategy, can improve depressive symptoms in women following an acute cardiac event. The worth of tailoring and targeting strategies to women's readiness to change behaviours as well as the likely benefit of providing a gender-based approach to care delivery. PMID- 21979961 TI - 2009/H1N1 infection in pregnancy association with adverse perinatal outcomes. PMID- 21979959 TI - EphrinA1-EphA2 signal induces compaction and polarization of Madin-Darby canine kidney cells by inactivating Ezrin through negative regulation of RhoA. AB - The epithelial cells exhibit either a columnar or a flat shape dependent on extracellular stimuli or the cell-cell adhesion. Membrane-anchored ephrinA stimulates EphA receptor tyrosine kinases as a ligand in a cell-cell contact dependent manner. The mechanism through which ephrinA1/EphA2 signal regulates the cell morphology remains elusive. We demonstrate here that ephrinA1/EphA2 signal induces compaction and enhanced polarization (columnar change) of Madin-Darby canine kidney epithelial cells by regulating Ezrin, a linker that connects plasma membrane and actin cytoskeleton. Activation of EphA2 resulted in RhoA inactivation through p190RhoGAP-A and subsequent dephosphorylation of Ezrin on Thr-567 phosphorylated by Rho kinase. Consistently, the cells expressing an active mutant of Ezrin in which Thr-567 was replaced with Asp did not change their shape in response to ephrinA1. Furthermore, depletion of Ezrin led to compaction and enhanced polarization without ephrinA1 stimulation, suggesting the role for active Ezrin in keeping the flat cell shape. Ezrin localized to apical domain irrespective of ephrinA1 stimulation, whereas phosphorylated Ezrin on the apical domain was reduced by ephrinA1 stimulation. Collectively, ephrinA1/EphA2 signal negatively regulates Ezrin and promotes the alteration of cell shape, from flat to columnar shape. PMID- 21979962 TI - Cytomegalovirus sero positivity dramatically alters the maternal CD8+ T cell repertoire and leads to the accumulation of highly differentiated memory cells during human pregnancy. AB - BACKGROUND: Human pregnancy offers an immunological challenge for the immunocompetent women accommodating an allogenic fetus, while continuing to combat potentially infectious disease. Cytomegalovirus (CMV) infects the majority of the human population and establishes lifelong persistence, which can lead to the oligoclonal expansion of differentiated T cells. Primary CMV infection and, less commonly, secondary infection during pregnancy can cause fetal disease and morbidity. The balance between maternal immune competence and viral pathogenicity is thus delicately poised. Our objective was to investigate the influence of CMV serostatus on maternal CD8+ T-cell phenotype and cytokine profile in an apparently healthy cohort of pregnant women. Furthermore, we assessed if CMV serostatus modulated changes in CD8 T cells during gestation. METHODS: CD8+ T cell phenotype was investigated in 87 pregnant women with samples obtained both during pregnancy [CMV immunoglobulin G (IgG) + n = 39, CMV IgG- n = 21] and in the early post-natal period (IgG+ n = 16, IgG- n = 11). Multiparameter flow cytometry was used to study T-cell phenotype and HLA-peptide tetramers identified CD8 T cells specific for CMV. Levels of 26 plasma cytokines, chemokines and chemokine receptors were assessed in a separate cohort of 20 women (IgG+ n = 10, IgG- n = 10) followed longitudinally during and after pregnancy. RESULTS: CMV seropositivity profoundly influenced the T cell repertoire and its dynamics during pregnancy. Naive CD8+ T-cells (CCR7+CD45RA+) were reduced by 50% in CMV seropositive women. The proportion of CD45RA effector cells was not increased in CMV-seropositive donors, although this population was more highly differentiated with reduced CD27 and CD28. However, there was a doubling in the proportion of CD45RA+ revertant memory cells (CCR7-CD45RA+) in seropositive donors. Moreover, seropositive women during late pregnancy demonstrated an accumulation of highly differentiated CMV-specific T-cells. T-cell activation independent of CMV was also seen in late pregnancy. No CMV-related changes in plasma cytokines, chemokines or their receptors were observed. CONCLUSIONS: Thus, CMV serostatus is a crucial consideration in studies of T cell memory and differentiation during pregnancy. The reduction in maternal naive T cells in CMV-seropositive donors could have implications for the maternal response to infections during pregnancy. These findings shed light on the delicate balance between host, fetus and chronic infection during healthy pregnancy and will inform studies in relation to the importance of CMV on maternal and fetal health. PMID- 21979963 TI - Transition to adult services. AB - The lack of focus on young people as a group with particular healthcare needs in medical training and the health service underpins the difficulty that we have experienced as a profession in improving transition in the UK. This article discusses current progress towards improving training in young people's health in the UK, the evidence base for transitional care in young people with chronic conditions with interventions that focus on staffing, service delivery and young people, a practice based approach for transitional care in young people with learning difficulties and complex needs, the need for monitoring and evaluation of transitional care, and the challenge of funding. PMID- 21979964 TI - A high-pressure single-crystal synchrotron diffraction study of NH4RbTe4O9.2H2O: stability of three different TeO(x) coordination polyhedra. AB - The crystal structure of ammonium rubidium nonaoxotetratellurate(IV) dihydrate has been studied as a function of pressure up to 7.40 GPa. The ambient-pressure structure is characterized by the co-existence of three different Te-O polyhedra (TeO(3), TeO(4) and TeO(5)), which are connected to form layers. NH(4)(+), H(2)O and Rb(+) are incorporated between the layers. Both the Rb1 position, which is located on a twofold axis, and the Rb2 position are partially occupied. The three different types of coordination polyhedra around Te(4+) are stable up to at least 5.05 GPa. No phase transition is observed. The fit of the unit-cell volume as a function of pressure gives a zero-pressure bulk modulus of 34 (1) GPa with a zero pressure volume of V(0) = 2620 (4) A(3) [B' = 1.4 (2)]. PMID- 21979965 TI - A tetragonal form of dysprosium orthomolybdate at room temperature. AB - In the present tetragonal modification of dysprosium orthomolybdate, Dy(2)(MoO(4))(3), the Dy, one Mo and one O atom are located on a mirror plane with Wyckoff symbol 4e, while another Mo atom is located on a fourfold inverse axis, Wyckoff symbol 2a. A single crystal was selected from a polycrystalline mixture of the Dy(2)O(3)-ZrO(2)-MoO(3) system and was stable at room temperature for at least three months. The structure refinement does not indicate the presence of Zr on the Dy sites (to within 1% accuracy). Thus, the stabilization of the tetragonal form is due to disordered positions for a second O atom and split positions for a third O atom that also maintain the DyO(7) coordination, which is not expected for short Dy-O distances [2.243 (6)-2.393 (5) A]. PMID- 21979966 TI - Tetraaquabis[5-(3-pyridyl-kappaN)pyrimidine]zinc(II) bis(trifluoromethanesulfonate): a novel cationic complex and three-dimensional hydrogen-bonded network. AB - The title compound, [Zn(C(9)H(7)N(3))(2)(H(2)O)(4)](CF(3)O(3)S)(2), contains an octahedral [ZnL(2)(H(2)O)(4)](2+) cationic complex with trans geometry (Zn site symmetry -1), and each 5-(3-pyridyl)pyrimidine (L) ligand is coordinated in a monodentate fashion through the pyridine N atom. In the extended structure, these complexes, with both hydrogen-bond acceptor (pyrimidine) and donor (H(2)O) functions, are linked to each other by intermolecular water-pyrimidine O-H...N hydrogen-bonding interactions, resulting in a double chain along the crystallographic a axis. The trifluoromethanesulfonate anions are integrated into the chains via O-H...O hydrogen bonds between the coordinated water and sulfonate O atoms. These double chains are associated into a novel three-dimensional network through interchain water-pyrimidine O-H...N hydrogen bonds. The asymmetric ligand plays an important role in constructing this unusual supramolecular structure. PMID- 21979967 TI - A binuclear zinc polymer with paddlewheel building units and intersecting helical chains based on a flexible 4-[(carboxymethyl)sulfanyl]benzoic acid ligand. AB - The asymmetric unit of the title compound, poly[{MU(4)-4 [(carboxylatomethyl)sulfanyl]benzoato}(N,N-dimethylformamide)zinc], [Zn(C(9)H(6)O(4)S)(C(3)H(7)NO)](n), consists of one crystallographically independent Zn(II) cation, one 4-[(carboxylatomethyl)sulfanyl]benzoate (L(2-)) ligand and one coordinated dimethylformamide (DMF) molecule. The zinc ion is coordinated by five O atoms from four separate L(2-) ligands and one DMF molecule, and the ZnO(5) unit displays a distorted square-based-pyramidal geometry. Two ZnO(5) units form a binuclear zinc-tetracarboxylate paddlewheel cluster, and these are bridged by L(2-) ligands to generate an intersecting helical chain (Zn(2+) ions as nodes), which is composed of right-handed (P) and left-handed (M) helices. Weak C-H...O hydrogen bonds extend the one-dimensional coordinated chain into a weakly bound three-dimensional supramolecular architecture. PMID- 21979968 TI - Magnesium and nickel(II) furan-2,5-dicarboxylate. AB - The salts hexaaquamagnesium furan-2,5-dicarboxylate, [Mg(H(2)O)(6)](C(6)H(2)O(5)), (I), and hexaaquanickel furan-2,5-dicarboxylate, [Ni(H(2)O)(6)](C(6)H(2)O(5)), (II), provide the first crystallographic characterization of the furan-2,5-dicarboxylate dianion. Both structures exhibit extensive three-dimensional hydrogen-bonding networks between the octahedral coordinated hexaaquametal(II) ions and the dicarboxylate anions. Although the two structures are not isomorphous, they contain essentially identical two dimensional slabs. The distinction between the structures is that these slabs are related by translation in (II), whereas adjacent slabs in (I) are reflected relative to each other by the action of a glide plane. The reflection occurs so that the local contacts between slabs are not changed, and thus the hydrogen-bond networks are identical except for the orientation of the water molecules at the interface between slabs. PMID- 21979969 TI - In situ synthesis of mononuclear copper(II) complexes of the new tridentate ligand bis[(3,5-dimethyl-1H-pyrazol-1-yl)methyl]amine. AB - Two mononuclear copper complexes, {bis[(3,5-dimethyl-1H-pyrazol-1-yl kappaN(2))methyl]amine-kappaN}(3,5-dimethyl-1H-pyrazole-kappaN(2))(perchlorato kappaO)copper(II) perchlorate, [Cu(ClO(4))(C(5)H(8)N(2))(C(12)H(19)N(5))]ClO(4), (I), and {bis[(3,5-dimethyl-1H-pyrazol-1-yl-kappaN(2))methyl]amine-kappaN}bis(3,5 dimethyl-1H-pyrazole-kappaN(2))copper(II) bis(hexafluoridophosphate), [Cu(C(5)H(8)N(2))(2)(C(12)H(19)N(5))](PF(6))(2), (II), have been synthesized by the reactions of different copper salts with the tripodal ligand tris[(3,5 dimethyl-1H-pyrazol-1-yl)methyl]amine (TDPA) in acetone-water solutions at room temperature. Single-crystal X-ray diffraction analysis revealed that they contain the new tridentate ligand bis[(3,5-dimethyl-1H-pyrazol-1-yl)methyl]amine (BDPA), which cannot be obtained by normal organic reactions and has thus been captured in the solid state by in situ synthesis. The coordination of the Cu(II) ion is distorted square pyramidal in (I) and distorted trigonal bipyramidal in (II). The new in situ generated tridentate BDPA ligand can act as a meridional or facial ligand during the process of coordination. The crystal structures of these two compounds are stabilized by classical hydrogen bonding as well as intricate nonclassical hydrogen-bond interactions. PMID- 21979970 TI - Self-assembled supramolecular sheet- and channel-type frameworks in the p phenetidinium hydrogen phthalate and cyclohexylaminium hydrogen phthalate hemihydrate salts. AB - The title compounds, p-phenetidinium hydrogen phthalate (or 4-ethoxyanilinium 2 carboxybenzoate), C(8)H(12)NO(+).C(8)H(5)O(4)(-), (I), and cyclohexylaminium hydrogen phthalate hemihydrate (or cyclohexylaminium 2-carboxybenzoate hemihydrate), C(6)H(14)N(+).C(8)H(5)O(4)(-).0.5H(2)O, (II), form two- and one dimensional supramolecular networks, respectively. In (I), the anionic-cationic network consists of R(3)(2)(6) and R(4)(4)(16) hydrogen-bonded rings forming a two-dimensional sheet along the (001) plane. In (II), O-H...O hydrogen bonds connect the glide-related anions, generating a supramolecular chain running parallel to [001] to which the cations are linked to form one-dimensional channels along [001]. The solvent water molecules, which reside on twofold axes, are trapped inside the molecular channels by N-H...O and O-H...O hydrogen bonds. PMID- 21979971 TI - Powder X-ray study of racemic (2RS,3RS)-5-amino-3-(4-phenylpiperazin-1-yl) 1,2,3,4-tetrahydronaphthalen-2-ol. AB - The title compound, C(20)H(25)N(3)O, an important precursor for the preparation of benzovesamicol analogues for the diagnosis of Alzheimer's disease, has been synthesized and characterized by FT-IR, and (1)H and (13)C NMR spectroscopic analyses. The crystal structure was analysed using powder diffraction as no suitable single crystal was obtained. The piperazine ring has a chair conformation, while the cyclohexene ring assumes a half-chair conformation. The crystal packing is mediated by weak contacts, principally by complementary intermolecular N-H...O hydrogen bonds that connect successive molecules into a chain. Further stabilization is provided by weak C-H...N contacts and by a weak intermolecular C-H...pi interaction. PMID- 21979972 TI - Water-induced pseudo-quadruple hydrogen-bonding motifs in xanthine-inorganic acid complexes. AB - In xanthinium nitrate hydrate [systematic name: 2,6-dioxo-1,2,3,6-tetrahydro-9H purin-7-ium nitrate monohydrate], C(5)H(5)N(4)O(2)(+).NO(3)(-).H(2)O, (I), and xanthinium hydrogen sulfate hydrate [systematic name: 2,6-dioxo-1,2,3,6 tetrahydro-9H-purin-7-ium hydrogen sulfate monohydrate], C(5)H(5)N(4)O(2)(+).HSO(4)(-).H(2)O, (II), the xanthine molecules are protonated at the imine N atom with the transfer of an H atom from the inorganic acid. The asymmetric unit of (I) contains a xanthinium cation, a nitrate anion and one water molecule, while that of (II) contains two crystallographically independent xanthinium cations, two hydrogen sulfate anions and two water molecules. A pseudo quadruple hydrogen-bonding motif is formed between the xanthinium cations and the water molecules via N-H...O and O-H...O hydrogen bonds in both structures, and leads to the formation of one-dimensional polymeric tapes. These cation-water tapes are further connected by the respective anions and aggregate into two dimensional hydrogen-bonded sheets in (I) and three-dimensional arrangements in (II). PMID- 21979973 TI - Weak C-H...O hydrogen bonds in anisaldehyde, salicylaldehyde and cinnamaldehyde. AB - In situ cryocrystallization has been employed to grow single crystals of 4 methoxybenzaldehyde (anisaldehyde), C(8)H(8)O(2), 2-hydroxybenzaldehyde (salicylaldehyde), C(7)H(6)O(2), and (2E)-3-phenylprop-2-enal (cinnamaldehyde), C(9)H(8)O, all of which are liquids at room temperature. Several weak C-H...O interactions of the types C(aryl)-H...O, C(formyl)-H...O and Csp(3)-H...O are present in these related crystal structures. PMID- 21979974 TI - A new polymorph of succinylcholinium diiodide: comparison of succinylcholinium structures. AB - The title compound {systematic name: trimethyl[2-({4-oxo-4-[2 (trimethylazaniumyl)ethoxy]butanoyl}oxy)ethyl]azanium diiodide}, C(14)H(30)N(2)O(4)(2+).2I(-), is a salt of the succinylcholinium cation. There is one formula unit in the asymmetric unit, represented by two anions and two halves of two cations which lie on centres of inversion. The component species are stabilized by electrostatic interactions, and C-H...I and C-H...O hydrogen bonds are also present. PMID- 21979975 TI - A variable-temperature study of 1,2-bis(dimethylamino)-1,2-bis(2,6 dimethylanilino)diborane. AB - The title compound, C(20)H(32)B(2)N(4), is monoclinic at ambient temperature but triclinic (pseudo-monoclinic) below 150 K. The structures of the two phases, determined at 200 and 120 K, respectively, are very similar, the molecular symmetry being crystallographic C(2) and approximate (local) C(2), respectively. There is significant pi conjugation within each N-B-N moiety, but none between them or between the N-B-N and arene moieties. PMID- 21979976 TI - High-Z' and twinning behavior in 3,4-dinitrobenzoic acid. AB - The title compound, C(7)H(4)N(2)O(6), (I), crystallizes in P1 with Z' = 4, but with no approximate or pseudosymmetry. The crystals were nonmerohedrally twinned, with at least four twin components related to the major moiety by 180 degrees rotations around the real b and c axes, and by 180 degrees rotation around the a* axis. The excessive twinning is not caused by a phase change from an untwinned room-temperature higher-symmetry polymorph. The molecules are planar chiral and, owing to the tilt angle of the nitro groups and the position of protonation, there are altogether eight conformers possible. Six of these theoretically possible eight conformers are realized in the solid-state structure of (I). Packing analysis and force-field calculations indicate that the largest part of the packing interactions does not originate from the hydrogen-bonding interactions, as one might initially be tempted to assume; pi-pi stacking and O(nitro)...pi interactions between neighboring molecules of (I) seem to be the dominant factor that determines the packing observed in the structure of this nitro-substituted benzoic acid derivative. PMID- 21979977 TI - Concomitant but disappearing: two polymorphs of 1,4-bis(tribromomethyl)benzene. AB - The title compound, C(8)H(4)Br(6), (I), initially crystallized from deuterochloroform as the comcomitant polymorphs (Ia) (prisms, space group P2(1)/n, Z = 2) and (Ib) (hexagonal plates, space group C2/c, Z = 4). The molecules in both forms display crystallographic inversion symmetry. All further attempts to crystallize the compound led exclusively to (Ib), so that (Ia) may be regarded as a 'disappearing polymorph'. Surprisingly, however, the density of (Ia) is greater than that of (Ib). The only significant difference between the molecular structures is the orientation of the CBr(3) groups. The molecular packing of both structures is largely determined by Br...Br interactions, although (Ia) also displays a C-H...Br hydrogen bond and both polymorphs display one Br...pi contact. For (Ia), six of the eight contacts combine to form a tube like substructure parallel to the a axis. For (Ib), the two shortest Br...Br contacts link 'half' molecules consisting of C-CBr(3) groups to form double layers parallel to (001) in the regions z ? 1/4, 3/4. PMID- 21979979 TI - 6-Chloro-2-oxindole: X-ray and DFT-calculated study. AB - The molecule of the title compound (systematic name: 6-chloroindolin-2-one), C(8)H(6)ClNO, is almost planar, with a dihedral angle of 1.13 (9) degrees between the planes of the constituent pyrrolidine and benzene rings. Centrosymmetric dimers are formed in the crystal structure by N-H...O hydrogen bonds, and these dimers are additionally linked by Cl...Cl and C-H...O interactions. Density functional theory (DFT) calculations at the B3LYP/6-31 G(d,p) level of theory were used to optimize the molecular structure and the geometry was best reproduced by optimization of two interacting molecules. The bond orders in the molecule, estimated using the natural bond orbitals (NBO) formalism, are consistent with the observed bond lengths. In particular, the contribution of the lone pair of electrons on the N atom to the N-C bond in the N C=O group is revealed. The measured IR spectrum of the compound shows a red shift of the N-H stretching frequency compared with the free molecule, due to the formation of the hydrogen bonds. PMID- 21979978 TI - Plumeridoid C from the Amazonian traditional medicinal plant Himatanthus sucuuba. AB - The stereochemistry of the iridoid plumeridoid C, C(15)H(18)O(7), was established by X-ray single-crystal structure analysis, giving (2'R,3R,4R,4aS,7aR)-methyl 3 hydroxy-4'-[(S)-1-hydroxyethyl]-5'-oxo-3,4,4a,7a-tetrahydro-1H,5'H spiro[cyclopenta[c]pyran-7,2'-furan]-4-carboxylate. The absolute structure of the title compound was determined on the basis of the Flack x parameter and Bayesian statistics on Bijvoet differences. The hydrogen-bond donor and acceptor functions of the two hydroxy groups are employed in the formation of O-H...O-bonded helical chains. PMID- 21979980 TI - N-butylpyridinium undecachlorocarbadodecaborate and comparison with similar compounds. AB - The title compound, C(9)H(14)N(+).CHB(11)Cl(11)(-), was obtained in the course of our continuing studies of the low-melting salts of closo- and nido-carborane cage anions with alkylpyridinium and dialkylimidazolium cations. The title compound is the first example of a pyridinium salt of a perchlorinated carborane anion. The structure consists of one N-butylpyridinium cation counterbalanced by one perchlorinated carborane cage anion per asymmetric unit. By changing the counter ion, different packings are observed, and to try to understand this the new structure is compared with five similar compounds. PMID- 21979981 TI - Ethyl 1-ethyl-7-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate: X-ray and DFT studies. AB - The basic building unit in the structure of the title compound, C(14)H(14)FNO(3), is pairs of molecules arranged in an antiparallel fashion, enabling weak C-H...O interactions. Each molecule is additionally involved in pi-pi interactions with neighbouring molecules. The pairs of molecules formed by the C-H...O hydrogen bonds and pi-pi interactions form ribbon-like chains running along the c axis. Theoretical calculations based on these pairs showed that, although the main intermolecular interaction is electrostatic, it is almost completely compensated by an exchange-repulsion contribution to the total energy. As a consequence, the dominating force is a dispersion interaction. The F atoms form weak C-F...H-C interactions with the H atoms of the neighbouring ethyl groups, with H...F separations in the range 2.59-2.80 A. PMID- 21979982 TI - Non-cystic fibrosis bronchiectasis. AB - Bronchiectasis is characterized by irreversible widening of the medium-sized airways, with inflammation, chronic bacterial infection and destruction of the bronchial walls. Exercise or inspiratory muscle training may improve quality of life and exercise endurance in people with non-cystic fibrosis bronchiectasis. Prolonged-use antibiotics improve clinical response rates, but may not reduce exacerbation rates or lung function. Surgery is often considered for people with extreme damage to one or two lobes of the lung who are at risk for severe infection or bleeding. In this review, the authors will focus on non-cystic fibrosis bronchiectasis, pointing out the differences in management when compared with the cystic fibrosis context, with special emphasis on surgical management. PMID- 21979983 TI - Successful conservative management of blunt right ventricular rupture in a patient with prior cardiac surgery. AB - Blunt cardiac trauma is one of the leading causes of death on site in motor vehicle accidents and frequently requires an emergent surgical intervention if the patient reaches the hospital. We experienced a rare case of blunt right ventricular disruption that was successfully managed by conservative therapy without surgery. PMID- 21979984 TI - Importance of accurate diagnosis using real-time three-dimensional echocardiography in the surgical treatment of congenital intramitral ring in infants. AB - Congenital mitral ring is a rare type of congenital mitral stenosis. There are two types of mitral ring: the intramitral ring and the supramitral ring. Intramitral rings are often associated with complex valve pathology, and therefore have a worse prognosis than supramitral rings, in which the mitral apparatus is usually normal. The role of echocardiography in the evaluation of the mitral valve apparatus is crucial, because it allows an identification of the types of malformation, their hemodynamic repercussion and early predictors of the outcome. We describe two cases of intramitral ring, the diagnostic challenge they provided, and the value of the information obtained using real-time three dimensional echocardiography in such cases. PMID- 21979985 TI - Cardiac displacement during off-pump coronary artery bypass grafting surgery: effect on sublingual microcirculation and cerebral oxygenation. AB - Cardiac displacement during off-pump coronary artery bypass (OPCAB) surgery causes a fall in cardiac output. Here, we investigate how this drop in systemic perfusion is transferred to the oxygenation of sublingual and cerebral tissue. Sublingual microcirculatory perfusion or microcirculatory hemoglobin oxygen saturation (MUHbSO(2)) measurements were performed using sidestream dark-field imaging and reflectance spectrophotometry, respectively (both n = 12). The cerebral tissue oxygenation index was measured by near-infrared spectrophotometry (n = 12). Cardiac output was calculated by pulse contour analysis of arterial pressure. Cardiac displacement reduced the cardiac output from 4.3 +/- 0.8 to 1.2 +/- 0.3 l/min (P < 0.05), paralleled by a decrease in MUHbSO(2) from 64.2 +/- 9.1 to 48.6 +/- 8.7% (P < 0.01). Cardiac displacement did not change functional capillary density, while red blood cell velocity decreased from 895 +/- 209 to 396 +/- 178 MUm/s (P<0.01). Cerebral tissue oxygenation index decreased from 69.5 +/- 4.0 to 57.4 +/- 8.5% (P<0.01) during cardiac displacement. After repositioning of the heart, all the values returned to baseline. Our data suggest that systemic hemodynamic alterations during cardiac displacement in OPCAB surgery reduce sublingual and cerebral tissue oxygenation. These findings are particularly important for patients at risk for the consequences of cerebral ischemia. PMID- 21979986 TI - Mitral valve repair in a patient with mitral regurgitation and osteogenesis imperfecta tarda. AB - We present the case of a 62-year-old female with a diagnosis of osteogenesis imperfecta and mitral valve regurgitation. The patient underwent a mitral valve repair without complications. We describe the case and our surgical technique. PMID- 21979987 TI - Preliminary experience in the use of an extracellular matrix to repair congenital heart diseases. AB - Congenital heart diseases are corrected early in life, so the surgical procedure has to maintain the maximum potential for growth. The quest for the ideal material for cardiac tissue repair is still ongoing. Here, we describe our preliminary experience with an extracellular matrix for cardiac and vascular tissue repair. Between August 2009 and April 2011, 26 patients underwent cardiac surgery using the CorMatrix patch for vascular repair (10 pulmonary artery, four ascending aorta, three aortic arch and one right ventricular outflow tract) or for valve reconstruction (five aortic, two tricuspid, one mitral and one pulmonary valve); in four cases, the repair was associated with pericardial closure using the same patch. There were no deaths, and at a mean follow-up of 13.2 months, there was no evidence of patch-related complications either in the vascular position or when used for valve repair. The ideal material for cardiac tissue repair should be haemostatic and resistant to tearing and calcification, and possibly one that will not induce an inflammatory cascade. In the last 25 months, we used an extracellular matrix for cardiac and vascular tissue repair. The patch is advocated to induce the patient's own tissue regeneration. The early results are encouraging, but a longer follow-up is needed to understand the real potential of this material. PMID- 21979988 TI - Mitohormesis: another pleiotropic effect of statins? PMID- 21979989 TI - Octreotide for the treatment of systemic lupus erythematosus: clinical effects and an in vitro study on its therapeutic mechanism. AB - Increased serum growth hormone (GH), together with high expression of growth hormone receptor on peripheral blood mononuclear cells (PBMCs), correlates with systemic lupus erythematosus (SLE) activity, suggesting that modulation of GH signaling may affect SLE activity. We explored the effects of octreotide (OCT), an analog of somatostatin that suppresses the release of GH, in SLE. The objectives of the study were to investigate effects of OCT on the proliferative capacity and cytokine expression of PBMCs from patients with SLE and to investigate therapeutic effects of OCT in patients with SLE. PBMCs from 13 active/inactive SLE patients and 11 controls were pretreated with or without GH and cultured with OCT. The proliferation of PBMCs was assessed by MTT assay and cytokines were quantified by ELISA. We compared the clinical response of 12 patients with SLE treated with OCT (100 ug twice daily) with 12 patients treated with prednisone over three months. OCT inhibited PBMC proliferation in a dose dependent manner and decreased the secretion of interleukin-6 (IL-6), interleukin 10 (IL-10), and interferon-gamma (IFN-gamma). Patients treated with OCT demonstrated improvements in SLEDAI, dsDNA titer, complement levels, and erythrocyte sedimentation rate (ESR). OCT inhibited PBMC proliferation and PBMC secretion of IL-6, IL-10 and IFN-gamma stimulated by GH. Treatment of patients with OCT resulted in clinical improvement in SLE. PMID- 21979990 TI - Left ventricular hypertrophy reclassification and death: application of the Recommendation of the American Society of Echocardiography/European Association of Echocardiography. AB - AIMS: Despite the American Society of Echocardiography (ASE)/European Association of Echocardiography (EAE) recommended the use of left ventricular (LV) mass to diagnose left ventricular hypertrophy (LVH), several laboratories continue to use only the septal thickness by M-mode because it appears easier to measure. Aim of the study was to investigate the discrepancy between the categorization of LVH severity based on measurement of septal thickness and indexed LV mass and the relative prognostic utility of these two methods. METHODS AND RESULTS: Observational cohort study. Unselected adults (>18 years) referred to the echocardiography laboratory for any indication had septal thickness and LV mass measured by the ASE/EAE formula using LV linear dimensions indexed to body surface area. LVH was categorized as absent, mild, moderate, and severe according to the ASE/EAE guideline sex-specific categorization cut-offs for septal thickness and LV mass. Follow-up for death was obtained from the national death index. A total of 2545 subjects (mean age 61.9 +/- 15.8, 53% women, mean diastolic septal thickness 10.3 +/- 2.2 mm, and mean indexed LV mass 107.5 +/- 37.3 g/m(2)) were enrolled. Agreement between the two methods in classifying LVH degree across the four categories was 52.6% (Kappa = 0.29, 95% confidence interval (CI): 0.26-0.32, P < 0.001). Of the 2513 subjects without severely thickened septum, 472 (18.9%) had severely abnormal indexed LV mass. Vice versa, of the 2045 individuals without severely abnormal indexed LV mass, only 4 (0.1%) were classified as severe LVH by septal thickness. After a mean follow-up of 2.5 +/- 1.2 years 121 (4.7%) deaths occurred. Using indexed LV mass partition values there was a graded association between LVH degree and survival. Compared with patients with normal indexed LV mass, the adjusted hazard ratio (HR) for death from all causes was 2.17 for mild (95% CI: 1.23-3.81, P = 0.007), 3.04 for moderate (95% CI: 1.76-5.24, P < 0.001), and 3.81 for severe (95% CI: 2.43-5.97, P < 0.001) LVH by indexed LV mass. The area under the receiver-operator characteristic (ROC) curve for the four degrees of LVH by indexed LV mass was superior [area under the curve (AUC) = 0.66] to that of the septal thickness partition values (AUC = 0.58, P = 0.0004). CONCLUSION: In a large cohort study of unselected adult outpatients referred to the echocardiography laboratory, the measurements of indexed LV mass applying the ASE/EAE recommended cut-offs yielded remarkable discrepancy in the diagnosis of LVH severity and offered prognostic information beyond that provided by septal thickness only criteria. PMID- 21979991 TI - Abnormal haemodynamic response to exercise in heart failure with preserved ejection fraction. AB - AIMS: Peak oxygen uptake (VO(2)) is diminished in patients with heart failure with preserved ejection fraction (HFpEF) suggesting impaired cardiac reserve. To test this hypothesis, we assessed the haemodynamic response to exercise in HFpEF patients. METHODS AND RESULTS: Eleven HFpEF patients (73 +/- 7 years, 7 females/4 males) and 13 healthy controls (70 +/- 4 years, 6 females/7 males) were studied during submaximal and maximal exercise. The cardiac output (Q(c), acetylene rebreathing) response to exercise was determined from linear regression of Q(c) and VO(2) (Douglas bags) at rest, ~30% and ~60% of peak VO(2), and maximal exercise. Peak VO(2) was lower in HFpEF patients than in controls (13.7 +/- 3.4 vs. 21.6 +/- 3.6 mL/kg/min; P < 0.001), while indices of cardiac reserve were not statistically different: peak cardiac power output [CPO = Q(c) * mean arterial pressure (MAP); HFpEF 1790 +/- 509 vs. controls 2119 +/- 581 L/mmHg/min; P = 0.20]; peak stroke work [SW = stroke volume (SV) * MAP; HFpEF 13 429 +/- 2269 vs. controls 13 200 +/- 3610 mL/mmHg; P = 0.80]. The DeltaQ(c)/DeltaVO(2) slope was abnormally elevated in HFpEF patients vs. controls (11.2 +/-3.6 vs. 8.3 +/- 1.5; P = 0.015). CONCLUSION: Contrary to our hypothesis, cardiac reserve is not significantly impaired in well-compensated outpatients with HFpEF. The abnormal haemodynamic response to exercise (decreased peak VO(2), increased DeltaQ(c)/DeltaVO(2) slope) is similar to that observed in patients with mitochondrial myopathies, suggesting an element of impaired skeletal muscle oxidative metabolism. This impairment may limit functional capacity by two mechanisms: (i) premature skeletal muscle fatigue and (ii) metabolic signals to increase the cardiac output response to exercise which may be poorly tolerated by a left ventricle with impaired diastolic function. PMID- 21979992 TI - Midsummer Eve in Sweden: a natural fluid challenge in patients with heart failure. AB - AIMS: Volume overload exacerbations in patients with chronic heart failure (HF) are associated with a dismal prognosis and are often triggered by dietary incompliance. We aimed to describe the effects of dietary changes on measures of fluid retention in HF patients. METHODS AND RESULTS: Thirty-one HF patients with an implantable defibrillator (age 64 +/- 11 years, ejection fraction 25 +/- 12%, median NT-proBNP 2090 ng/L, resynchronization therapy: n= 25) were followed by daily body weight (BW) (telemonitoring) and intrathoracic impedance (by the implanted device) around Swedish Midsummer 2009, a holiday traditionally celebrated with meals including salty fish dishes and ample intake of fluids. Midsummer Eve celebrations caused a distinct and rapid increase in BW and a decrease in impedance indicating increased fluid retention. Compared with baseline values, peak BW increased by 1225 g [interquartile range (IQR) 475-2013 g)] which was accompanied by a decrease in impedance (3 Omega; IQR -5.2 to -1.2) and a clear deflection on the impedance-based fluid detection algorithm (OptiVol) that crossed the preset fluid-alert threshold six times following Midsummer. Body weight and impedance values were normalized after a period of 20 and 8 days, respectively. A clustering of minor clinical events following Midsummer suggests a possible adverse impact of dietary incompliance. However, none of the patients were hospitalized for HF. CONCLUSIONS: Dietary incompliance, e.g. on the occasion of a ceremonial meal, may lead to marked disturbances in the fluid balance of patients with HF reflected by increased BW and decreased intrathoracic impedance. These findings underline the importance of maintaining stable volume conditions in HF patients. PMID- 21979993 TI - Ventricular arrhythmias originating from the aortomitral continuity: an uncommon variant of left ventricular outflow tract tachycardia. AB - AIMS: Ventricular arrhythmias arising from the fibrous rings have been demonstrated, but knowledge about the aortomitral continuity (AMC) as a source of the arrhytmias is still limited. The objective is to describe the characteristics of ventricular arrhythmias originating from the AMC in patients without structural heart disease. METHODS AND RESULTS: Ten patients with ventricular tachycardia (VT) and/or premature ventricular contractions, who had been successfully treated by catheter ablation at the AMC beneath the aortic valve, were enrolled. Clinical data and electrocardiographic characteristics were analysed. Three of the 10 patients had previously registered episodes of supraventricular tachycardia and had undergone catheter ablation of atrioventricular nodal reentrant tachycardia (AVNRT). In four patients with anterior AMC location, early R/S wave transition was found in the precordial leads, with equal R and S amplitudes in V2, rS in V1, and R in V3. In six patients whose VT arose from the middle part of the AMC, we demonstrated a special ('rebound') transition pattern, with which equal R and S amplitudes occurred in V2, and high R waves in V1 and V3. In the anterior AMC location, the S/R ratios in leads V1 and V2 were >1 and statistically significantly higher than those located in the middle (V1: 1.59 vs. 0.23, P< 0.001; V2: 1.52 vs. 0.41, P< 0.01). CONCLUSIONS: We report a series of ventricular arrhythmias arising from the AMC with different R/S wave transition patterns in the precordial leads on the electrocardiogram. There may be a relationship between ventricular arrhythmias from AMC and AVNRT. PMID- 21979995 TI - Use of implantable loop recorders in patients with Brugada syndrome and suspected risk of ventricular arrhythmia. AB - AIMS: Implantable cardioverter defibrillator (ICD) therapy is recommended in patients with Brugada syndrome (BS) who experienced aborted sudden cardiac death (SCD) or syncope while the risk stratification of ventricular arrhythmias is a difficult step in patients with atypical symptoms. Implantable loop recorder (ILR) use has been proposed to study patients with unexplained recurrent syncopal events, but its usefulness remains to be defined in patients with BS. In this retrospective study we aimed to investigate the effectiveness of ILR as a diagnostic tool in BS patients suspected of low or moderate risk of SCD. METHODS AND RESULTS: We gathered data from 11 ILR recipients with supposed risk of ventricular arrhythmia, issue of Amiens registry of 204 patients with BS. We reported clinical events before and after implant, electrocardiogram (ECG) characteristics, ILR findings, and its limitations as well as tried to specify ILR utility in diagnosis approach and its consequent contribution to guide the optimal therapy. Within the 11 patients (8 men, 3 women), 9 were symptomatic, and 5 had a spontaneous Type 1 ECG pattern. During mean follow-up period of 33 months, 8 patients had a recurrence of symptoms with a mean delay of 9 months after implant. Bradycardia (two atrioventricular blocks and two sinus bradycardia) was detected in four out of eight patients (50%), and there was no ventricular arrhythmia in any patient during symptomatic events which included six vasovagal syncopes and two epileptic seizures. Two initially asymptomatic patients did not experience any symptoms after ILR implant and their ILR recordings did not reveal any arrhythmias. CONCLUSION: The ILR contributed to the exclusion of a ventricular arrhythmia as a mechanism of an atypical syncope in patients with electrocardiographic BS and the suspension of the ICD implant. Episodes of transient symptomatic bradycardia were the most common findings suggesting the vagal mechanism of symptoms. The use of ILR should be considered in selected patients with atypical syncope and spontaneous or transient Type 1 ECG pattern. PMID- 21979994 TI - Role of implantable cardioverter defibrillator therapy in patients with acquired long QT syndrome: a long-term follow-up. AB - AIMS: The use of implantable cardioverter defibrillators (ICD) in patients with torsade de pointes (TdP) and ventricular fibrillation in the presence of acquired long QT syndrome (aLQTS) is under debate, partly due to the fact that aLQTS is potentially reversible and currently no long-term follow-up data are available. We aimed to evaluate the long-term follow-up of patients with acquired long QT syndrome (aLQTS) who had received an implantable cardioverter defibrillator (ICD) for secondary prevention of sudden cardiac arrest (SCA). METHOD AND RESULTS: Over a 10 year period, 43 patients with an ICD after survived cardiac arrest (SCA) due to an aLQTS were included [female n= 27 (63%); mean age 61 +/- 16 years]. There was no clinical evidence for congenital LQTS (Schwartz score 1.25 +/- 0.8). Structural heart disease was present in 29 patients (47%; ischaemic n= 13; dilated cardiomyopathy n= 9; mean EF 41%+/- 12). The most common proarrhythmic trigger happened to be antiarrhythmic drugs (n= 34; 79%). Other triggers included contrast agent (n= 1), haloperidol (n= 2), severe hypokalaemia (n= 2), drug abuse/alcohol (n= 2), and mere severe bradycardia (n= 2). Under trigger QTc interval measured 536 +/- 58 vs. 438 +/- 33 ms without trigger (P< 0.001). During a mean follow-up of 84 +/- 55 months, appropriate shocks occurred in 19 patients (44%); inappropriate shocks in 13 patients (30%; only inappropriate n= 3). Appropriate shocks were almost as common in patients without as in those with structural heart disease (35 vs. 48%; P= 0.32). None of the patients were re exposed to the initial trigger during the follow-up period. Beta-blocker medication did not prevent ICD shocks (12 of 19 vs. 11 of 24 on medication). CONCLUSION: Appropriate ICD shocks are a common finding in patients with aLQTS and SCA irrespective of the underlying cause or structural heart disease. Thus, even in the presence of relevant acquired proarrhythmia ICD may be beneficial. PMID- 21979996 TI - Autofluorescence of the cells in human subretinal fluid. AB - PURPOSE: The origin of autofluorescence in the subretinal space and the autofluorescence properties of the cells were investigated in surgically collected subretinal fluid. METHODS: Subretinal fluid was surgically collected from four eyes of patients with rhegmatogenous retinal detachment (three eyes) and Coats' disease (one eye). After cytocentrifuge preparation of the cells in the fluid and immunofluorescence staining, a cytologic examination was conducted by using confocal scanning laser microscopy. The autofluorescence of the cells was elucidated by measuring the fluorescence spectra with spectroscopy, to obtain different excitation laser light emission fingerprints. RESULTS: The cells from the subretinal fluid were classified into three types: CD68-negative cells containing numerous pigmented granules, CD68-positive cells containing few pigments, and CD68-negative cells with no pigmented granules. Autofluorescence was observed in the inclusions of the cells classified into the former two types. When the cells were excited by a 458- or 488-nm laser light, emission spectra in autofluorescence showed little difference between CD68-positive and -negative cells. Peak analysis confirmed that the two types of cells showed the same emission peaks within this range of excitation light. CONCLUSIONS: Autofluorescent inclusions appeared in the CD68-positive and -negative cells in the subretinal fluid. The macrophages in the subretinal fluid possess autofluorescence that is spectroscopically similar to lipofuscin. Autofluorescence of macrophages can be attributed to degenerated outer segments and debris from apoptotic photoreceptors. Clinicians should consider migration of macrophages, in addition to retinal pigment epithelium, as the possible source when abnormal fundus autofluorescence is observed using an ordinary set of fluorescence filters. PMID- 21979997 TI - Supplementation with all three macular carotenoids: response, stability, and safety. AB - PURPOSE: This study was designed to investigate serum and macular response to, and safety of supplementation with, meso-zeaxanthin (MZ), lutein (L), and zeaxanthin (Z), the carotenoids that constitute macular pigment (MP). METHODS: Forty-four healthy subjects were recruited into this randomized, placebo controlled, clinical trial. Subjects consumed one tablet per day containing 10.6 mg MZ, 5.9 mg L, and 1.2 mg Z (intervention, I group) or placebo (P group). The spatial profile of MP optical density (MPOD) was measured with customized heterochromatic flicker photometry (cHFP), and serum concentrations of L and Z were quantified by using high performance liquid chromatography (HPLC). Subjects were assessed at baseline and at 3 and 6 months. Clinical pathology analysis was performed at baseline and 6 months. RESULTS: Serum concentrations of L and Z increased significantly in the I group (P = 0.001 and 0.003, respectively) and remained stable in the P group (P > 0.05). There was a significant increase in central MPOD in the I group (0.25 degrees : P = 0.001; 0.5 degrees : P = 0.001), with no significant change in the P group (P > 0.05). Clinical pathology analysis confirmed that all variables remained within the normal reference range, with the exception of total cholesterol and low-density lipoprotein (LDL), which exhibited baseline values outside the accepted normal reference range before supplementation. CONCLUSIONS: Subjects supplemented with MZ, L, and Z exhibited significant increases in serum concentrations of these carotenoids and a subsequent increase in central MPOD. Pathology analysis suggested no adverse clinical implications of consuming these carotenoids. (http://isrctn.org number, ISRCTN60816411). PMID- 21979998 TI - Quantitative evaluation of changes in eyeball shape in emmetropization and myopic changes based on elliptic fourier descriptors. AB - PURPOSE: To evaluate changes in eyeball shape in emmetropization and myopic changes using magnetic resonance imaging (MRI) and elliptic Fourier descriptors (EFDs). METHODS: The subjects were 105 patients (age range, 1 month-19 years) who underwent head MRI. The refractive error was determined in 30 patients, and eyeball shape was expressed numerically by principal components analysis of standardized EFDs. RESULTS: In the first principal component (PC1; the oblate-to prolate change), the proportion of variance/total variance in the development of the eyeball shape was 76%. In all subjects, PC1 showed a significant correlation with age (Pearson r = -0.314; P = 0.001), axial length (AL, r = -0.378; P < 0.001), width (r = -0.200, P = 0.0401), oblateness (r = 0.657, P < 0.001), and spherical equivalent refraction (SER, r = 0.438; P = 0.0146; n = 30). In the group containing patients aged 1 month to 6 years (n = 49), PC1 showed a significant correlation with age (r = -0.366; P = 0.0093). In the group containing patients aged 7 to 19 years (n = 56), PC1 showed a significant correlation with SER (r = 0.640; P = 0.0063). CONCLUSIONS: The main deformation pattern in the development of the eyeball shape from oblate to prolate was clarified by quantitative analysis based on EFDs. The results showed clear differences between age groups with regard to changes in the shape of the eyeball, the correlation between these changes, and refractive status changes. PMID- 21979999 TI - High glucose induces mitochondrial morphology and metabolic changes in retinal pericytes. AB - PURPOSE: Mitochondrial dysfunction is known to play a role in retinal vascular cell loss, a prominent lesion of diabetic retinopathy. High glucose (HG) has been reported to induce mitochondrial fragmentation and dysfunction in retinal endothelial cells, contributing to apoptosis. In this study, the effects of HG on mitochondrial morphology, membrane potential, and metabolic changes and whether they could contribute to HG-induced apoptosis in retinal pericytes were investigated. METHODS: Bovine retinal pericytes (BRPs) were grown in normal or HG medium for 7 days. Both sets of cells were double stained with mitochondrial membrane potential-independent dye and tetramethylrhodamine-ethyl-ester perchlorate (TMRE) and imaged by confocal microscopy. The images were analyzed for average mitochondria shape, by using form factor and aspect ratio values, and membrane potential changes, by using the ratio between the red and green dye. BRPs grown in normal or HG medium were analyzed for transient changes in oxygen consumption and extracellular acidification with a flux analyzer and apoptosis by TUNEL assay. RESULTS: BRPs grown in HG media exhibited significant fragmentation of mitochondria and increased membrane potential heterogeneity compared with the BRPs grown in normal medium. Concomitantly, BRPs grown in HG showed reduced steady state and maximum oxygen consumption and reduced extracellular acidification. Number of TUNEL-positive pericytes was increased in HG condition as well. CONCLUSIONS: In HG condition, mitochondria of retinal pericytes display significant fragmentation, metabolic dysfunction, and reduced extracellular acidification. The detrimental effects of HG on mitochondrial function and cellular metabolism could play a role in the accelerated apoptosis associated with the retinal pericytes in diabetic retinopathy. PMID- 21980001 TI - Comparative human aqueous dynamics study between black and white subjects with glaucoma. AB - PURPOSE: To compare the baseline aqueous humor dynamics in white Caucasians and patients of African origin with previously untreated primary open-angle glaucoma (POAG) or ocular hypertension (OHT). METHODS: Ninety-one participants were enrolled in this prospective, observational controlled study: 34 black subjects with POAG or OHT, 32 white Caucasian participants with POAG or OHT, and 12 black and 13 white healthy volunteers as the controls. All aqueous humor parameters were taken between 9 AM and 12 noon on the same day. Intraocular pressure (IOP) was measured by pneumatonometer; morning aqueous humor flow rate was measured by fluorophotometry and trabecular outflow facility by electronic Schiotz tonography. Uveoscleral outflow was calculated by using Goldmann's equation with assumed episcleral venous pressure of 8, 9, 10, and 11 mm Hg. Differences among groups were analyzed with parametric and nonparametric tests and the relationship between aqueous dynamics parameters were evaluated with linear regression analyses. RESULTS: The POAG/OHT groups had similar IOP (white, 24.6 +/- 3.0 mm Hg; black, 24.3 +/- 4.0 mm Hg; comparison by Holm's sequential Bonferroni method (HBonf): P(HBonf) = 0.51), outflow facility (white, 0.13 +/- 0.09 MUL/min/mm Hg; black, 0.13 +/- 0.07 MUL/min/mm Hg; P(HBonf) = 0.87), aqueous flow (white, 2.36 +/- 0.63 MUL/min; black, 2.35 +/- 0.53 MUL/min; P(HBonf) = 0.95), and uveoscleral outflow (white, 0.42 +/- 1.59 MUL/min; black, 0.58 +/- 1.17 MUL/min; P(HBonf) = 1.78). POAG/OHT groups had significantly higher IOP and lower outflow facility than their healthy counterparts (P < 0.01). Black participants had significant thinner corneas (540 +/- 37 MUm vs. 564 +/- 36 MUm) than those of white participants (P = 0.002). CONCLUSIONS: The aqueous humor dynamics of black African and white Caucasian patients with POAG or OHT have no significant differences. However, the significantly thinner corneas of the black patients may be masking potential differences in outflow facility and IOP measurements between the racial groups. PMID- 21980000 TI - Gene expression changes in steroid-induced IOP elevation in bovine trabecular meshwork. AB - PURPOSE: To determine whether gene expression changes occur in the trabecular meshwork (TM) of cow eyes with steroid-induced intraocular pressure (IOP) elevation. METHODS: Adult female Braford cows (n = 4) were subjected to uniocular prednisolone acetate treatment for 6 weeks. IOP was monitored with an applanation tonometer. At the conclusion of the experiment, animals were euthanized, eyes were enucleated, and the TM was dissected and stored in an aqueous nontoxic tissue storage reagent. RNA was extracted and subjected to microarray analysis using commercial oligonucleotide bovine arrays. Some of the genes differentially expressed between control and experimental eyes were confirmed by quantitative RT PCR and some of the respective proteins were studied by immunoblotting. RESULTS: IOP began to increase after 3 weeks of treatment, reaching a peak 2 weeks later. IOP differences between corticosteroid-treated and fellow control eyes were 6 +/- 1 mm Hg (mean +/- SD) at the conclusion of the study. Microarray analysis revealed that expression of 258 genes was upregulated, whereas expression of 187 genes was downregulated in the TM of eyes with steroid-induced IOP elevation. Genes identified to be differentially expressed include genes coding for cytoskeletal proteins, enzymes, growth and transcription factors, as well as extracellular matrix proteins and immune response proteins. A number of relevant gene networks were detected by bioinformatic analysis. CONCLUSIONS: Steroid induced IOP elevation alters gene expression in the bovine TM. Identification of genes with changing expression in this model of open-angle glaucoma may help elucidate the primary changes occurring at the molecular level in this condition. PMID- 21980003 TI - Increased proliferation and replicative lifespan of isolated human corneal endothelial cells with L-ascorbic acid 2-phosphate. AB - PURPOSE: To explore an alternative culture method for human corneal endothelial cells (HCECs) and to examine the effect of l-ascorbic acid 2-phosphate (Asc-2P) on the growth of these cells. METHODS: The influence of various mitogens, extracellular matrices (ECMs), and Asc-2P on growth of cultured HCECs was examined. HCECs were obtained from donors ranging in age from 12 to 74 years, and primary cultures and subcultures were performed with or without Asc-2P. Expanded HCECs were characterized with immunostaining and reverse transcription polymerase chain reaction (RT-PCR) and evaluated for generation of 8-hydroxy-2 deoxyguanosine (8-OHdG) with immunostaining and an enzyme-linked immunosorbent assay (ELISA). RESULTS: Culture with Asc-2P and bFGF on atelocollagen promoted the proliferation of HCECs in both primary cultures and subcultures as efficiently as conventional culture using ECM derived from bovine corneal endothelial cells. Zonula occludens-1, N-cadherin, connexin 43, and Na+/K+-ATPase were localized at plasma membranes of cultured HCECs. mRNAs of the voltage dependent anion channels (VDAC2 and VDAC3), sodium bicarbonate cotransporter member 4 (SLC4A4), and chloride channel proteins (CLCN2 and CLCN3) were detected by RT-PCR. During multiple passages, cultures without Asc-2P showed a decrease in growth and irregular cell morphology, whereas cultures with Asc-2P sustained cell growth and maintained the characteristic polygonal morphology. ELISA for 8-OHdG showed that the levels in mitochondrial DNA significantly decreased when HCECs were subcultured with Asc-2P. CONCLUSIONS: Combination of Asc-2P and bFGF on atelocollagen allows successful culture for HCECs. Asc-2P extends the lifespan of cultured HCECs, partly due to protection against oxidative DNA damage. PMID- 21980002 TI - Relationships between visual field sensitivity and spectral absorption properties of the neuroretinal rim in glaucoma by multispectral imaging. AB - PURPOSE: To investigate the relationship between neuroretinal rim (NRR) differential light absorption (DLA, a measure of spectral absorption properties) and visual field (VF) sensitivity in primary open-angle glaucoma (POAG). METHODS: Patients diagnosed with (n = 22) or suspected of having (n = 7) POAG were imaged with a multispectral system incorporating a modified digital fundus camera, 250-W tungsten-halogen lamp, and fast-tuneable liquid crystal filter. Five images were captured sequentially within 1.0 second at wavelengths selected according to absorption properties of hemoglobin (range, 570-610 nm), and a Beer-Lambert law model was used to produce DLA maps of residual NRR from the images. Patients also underwent VF testing. Differences in NRR DLA in vertically opposing 180 degrees and 45 degrees sectors either side of the horizontal midline were compared with corresponding differences in VF sensitivity on both decibel and linear scales by Spearman's rank correlation. RESULTS: The decibel VF sensitivity scale showed significant relationships between superior-inferior NRR DLA difference and sensitivity differences between corresponding VF areas in 180 degrees NRR sectors (Spearman rho = 0.68; P < 0.0001), superior-/inferior-temporal 45 degrees NRR sectors (rho = 0.57; P < 0.002), and superior-/inferior-nasal 45 degrees NRR sectors (rho = 0.59; P < 0.001). Using the linear VF sensitivity scale significant relationships were found for 180 degrees NRR sectors (rho = 0.62; P < 0.0002) and superior-inferior-nasal 45 degrees NRR sectors (rho = 0.53; P < 0.002). No significant difference was found between correlations using the linear or decibel VF sensitivity scales. CONCLUSIONS: Residual NRR DLA is related to VF sensitivity in POAG. Multispectral imaging may provide clinically important information for the assessment and management of POAG. PMID- 21980004 TI - Predicting benign course and prolonged illness in lower respiratory tract infections: a 13 European country study. AB - BACKGROUND: Clinicians and patients are often uncertain about the likely clinical course of community-acquired lower respiratory tract infection (LRTI) in individual patients. We therefore set out to develop a prediction rule to identify patients at risk of prolonged illness and those with a benign course. METHODS: We determined which signs and symptoms predicted prolonged illness (moderately bad symptoms lasting >3 weeks after consultation) in 2690 adults presenting in primary care with LRTI in 13 European countries by using multilevel modelling. RESULTS: 212 (8.1%) patients experienced prolonged illness. Illness that had lasted >5 days at the time of presentation, >1 episode of cough in the preceding year, chronic use of inhaled pulmonary medication and diarrhoea independently predicted prolonged illness. Applying a rule based on these four variables, 3% of the patients with <= 1 variable present (n = 955, 37%) had prolonged illness. Patients with all four variables present had a 30% chance of prolonged illness (n = 71, 3%). CONCLUSIONS: Most patients with acute cough (>90%) recover within 3 weeks. A prediction rule containing four clinical items had predictive value for the risk of prolonged illness, but given its imprecision, appeared to have little clinical utility. Patients should be reassured that they are most likely to recover within three weeks and advised to re-consult if their symptoms persist beyond that period. PMID- 21980006 TI - Cancer survivorship: focusing on future research opportunities. PMID- 21980007 TI - Cancer survivors: a booming population. AB - BACKGROUND: In this first article of what is planned to be an annual series, we examine the history of cancer prevalence reporting and the role that these annual figures play in guiding the direction of cancer control research, and specifically the science of cancer survivorship. For this inaugural year, we focus on the confluence of the growing number of survivors and population aging, and the impact these combined trends will have on cancer survivorship in the future. METHODS: State or metro area-level cancer incidence and prevalence data were collected from 9 registries via the Surveillance, Epidemiology, and End Results Program. The complete prevalence method was used to estimate prevalence for 2008 and the Prevalence, Incidence Approach Model method was used to project prevalence data through 2020, assuming flat cancer incidence and survival trends but dynamic U.S. population projections. RESULTS: As of January 2008, the number of cancer survivors is estimated at 11.9 million. Approximately 60% of cancer survivors are age 65 or older, and by the year 2020, it is estimated that 63% of cancer survivors will be age 65 or older. CONCLUSIONS: Improved survival and population aging converge to generate a booming population of older adult cancer survivors, many of whom have multiple complex health conditions and unique survivorship needs. This demographic shift has important implications for future health care needs and costs of the U.S. population. IMPACT: The findings provide information critical for guiding cancer prevention and control research and service provision. PMID- 21980009 TI - Support for caregivers of cancer patients: transition after active treatment. AB - Family caregivers provide uncompensated care and assistance to a family member who has cancer. When patients move through the care trajectory into the survivorship phase, roles and demands of caregivers change and caregivers assume responsibility to assist with coordination of ongoing care. The goal of this article is to describe aspects of caregiver experiences and the roles of caregivers as patients transition from active cancer treatment into the first and early phase of cancer care. Residual problems for patients and caregivers remain for some period of time. PMID- 21980008 TI - Economic burden of cancer in the United States: estimates, projections, and future research. AB - The economic burden of cancer in the United States is substantial and expected to increase significantly in the future because of expected growth and aging of the population and improvements in survival as well as trends in treatment patterns and costs of care following cancer diagnosis. In this article, we describe measures of the economic burden of cancer and present current estimates and projections of the national burden of cancer in the United States. We discuss ongoing efforts to characterize the economic burden of cancer in the United States and identify key areas for future work including developing and enhancing research resources, improving estimates and projections of economic burden, evaluating targeted therapies, and assessing the financial burden for patients and their families. This work will inform efforts by health care policy makers, health care systems, providers, and employers to improve the cancer survivorship experience in the United States. PMID- 21980010 TI - Methods to assess adverse health-related outcomes in cancer survivors. AB - Designing a study focused on adverse health-related outcomes among cancer survivors is complex. Similarly, reading and interpreting the findings of a survivorship-focused study requires an appreciation of the complexities of study design, potential biases, confounding factors, and other limitations. The topic areas are broad--study design, comparison populations, measures of risk, key health outcomes of interest, potential modifying factors to consider. With brevity, this article includes basic information to consider within these areas as well as examples and concepts intended to advance the science of survivorship research and encourage further reading and exploration. PMID- 21980011 TI - Consideration of quality of life in cancer survivorship research. AB - Quality of life assessment has a number of important applications in research on cancer survivors. These applications include use in observational studies to characterize the nature and extent of problems patients experience as well as use in randomized controlled trials to evaluate the relative impact of different cancer treatments or to evaluate the efficacy of interventions designed to improve patient well-being. The aims of this article are to provide an overview of the construct of quality of life and describe strategies commonly used to measure quality of life in adult cancer survivors. In addition, several priorities for future research are identified that involve how quality of life is measured, in whom it is measured, and what uses are made of quality of life data in the clinical care of cancer survivors. PMID- 21980012 TI - Cancer survivorship research: a review of the literature and summary of current NCI-designated cancer center projects. AB - The number of cancer survivors and the amount of cancer survivorship research have grown substantially during the past three decades. This article provides a review of interventional and observational cancer survivorship research efforts as well as a summary of current cancer survivorship research projects being conducted by National Cancer Institute-designated cancer centers in an effort to identify areas that need further attention. PMID- 21980014 TI - Survivors at higher risk for adverse late outcomes due to psychosocial and behavioral risk factors. AB - Cancer survivors face significant morbidity and mortality associated with their disease and treatment regimens, some of which can be improved through modifying behavioral and psychosocial risk factors. This article examines risk factors for adverse late effects that contribute to morbidity and mortality in cancer survivors, provides a literature review on interventions to modify these risks factors, and summarizes the national recommendations and associated current practices for identifying and managing these risk factors. Finally, future directions for research and clinical practice are discussed. PMID- 21980013 TI - Role of genetic susceptibility in development of treatment-related adverse outcomes in cancer survivors. AB - Clear and unambiguous associations have been established between therapeutic exposures and specific complications. However, considerable interindividual variability is observed in the risk of developing an outcome for a given therapeutic exposure. Genetic predisposition and especially its interaction with therapeutic exposures can potentially exacerbate the toxic effect of treatment on normal tissues and organ systems, and can possibly explain the interindividual variability. This article provides a brief overview of the current knowledge about the role of genomic variation in the development of therapy-related complications. Relatively common outcomes with strong associations with therapeutic exposures, including cardiomyopathy, obesity, osteonecrosis, ototoxicity, and subsequent malignancies are discussed here. To develop a deeper understanding of the molecular underpinnings of therapy-related complications, comprehensive and near-complete collection of clinically annotated samples is critical. Methodologic issues such as study design, definition of the endpoints or phenotypes, identification of appropriate and adequately sized study population together with a reliable plan for collecting and maintaining high quality DNA, and selection of an appropriate approach or platform for genotyping are also discussed. Understanding the etiopathogenetic pathways that lead to the morbidity is critical to developing targeted prevention and intervention strategies, optimizing risk-based health care of cancer survivors, thus minimizing chronic morbidities and improving quality of life. PMID- 21980015 TI - Design and conduct of intervention-based research among cancer survivors. AB - Intervention trials in cancer survivors play an important and growing role in complementing the wealth of knowledge obtained from observational studies about how lifestyle can improve clinical, physiologic, and psychological outcomes. As the number of intervention trials grows, attention to study design and reporting is essential to establishing a high-quality data pool from which to make evidence based recommendations and guidelines. We highlight several key issues important to the design and interpretation of intervention trials in cancer survivors. Intervention dose and duration both matter in trials of cancer survivors, yet few trials have evaluated different intervention doses and few intervention trials with multiyear follow-up exist. Finally, there is a need for interventions both of longer duration and those that take a practical trials approach and reflect clinical practice to speed implementation within practice and improve outcomes for cancer survivors. PMID- 21980016 TI - Impact of survivorship-based research on defining clinical care guidelines. AB - The growing number of individuals living five or more years from cancer diagnosis underscores the importance of providing guidance about potential late treatment effects to clinicians caring for long-term cancer survivors. Late treatment effects are commonly experienced by cancer survivors, increase in prevalence with aging, produce substantial morbidity, and predispose to early mortality. Findings from survivorship research permit providers to anticipate health risks among predisposed survivors and facilitate their access to interventions to prevent, detect, or rehabilitate cancer-related morbidity. This article reviews the impact that survivorship research has made in defining clinical care guidelines and the challenges that remain in developing and translating research findings into health screening recommendations that can optimize the quality and duration of survival after cancer. PMID- 21980017 TI - Dissemination and translation: a frontier for cancer survivorship research. AB - As the field of survivorship research grows, the need for translation is imperative to expand new knowledge into arenas that directly impact survivors. This commentary seeks to encourage research focused on dissemination and translation of survivorship interventions and programs, including practice-based research. We overview diffusion, dissemination and translation in the context of cancer survivorship and present the RE-AIM and Knowledge to Action frameworks as approaches that can be used to expand research into communities. Many academic, governmental, and community-based organizations focus on cancer survivor. Future survivorship research should contribute to harmonizing these assets to identify effective interventions, maximize their reach and adoption, and integrate promising practices into routine care. PMID- 21980018 TI - A framework for cancer survivorship research and translation to policy. AB - Awareness has grown over the past few years that needs specific to cancer survivors have long been neglected. Clinicians and policy makers continue to struggle, however, with exactly how to address these needs. We present a comprehensive framework for survivorship research and couple it with a model for translating research into policy, using two examples for illustration. PMID- 21980019 TI - Laterality of temporoparietal causal connectivity during the prestimulus period correlates with phonological decoding task performance in dyslexic and typical readers. AB - We examined how effective connectivity into and out of the left and right temporoparietal areas (TPAs) to/from other key cortical areas affected phonological decoding in 7 dyslexic readers (DRs) and 10 typical readers (TRs) who were young adults. Granger causality was used to compute the effective connectivity of the preparatory network 500 ms prior to presentation of nonwords that required phonological decoding. Neuromagnetic activity was analyzed within the low, medium, and high beta and gamma subbands. A mixed-model analysis determined whether connectivity to or from the left and right TPAs differed across connectivity direction (in vs. out), brain areas (right and left inferior frontal and ventral occipital-temporal and the contralateral TPA), reading group (DR vs. TR), and/or task performance. Within the low beta subband, better performance was associated with increased influence of the left TPA on other brain areas across both reading groups and poorer performance was associated with increased influence of the right TPA on other brain areas for DRs only. DRs were also found to have an increase in high gamma connectivity between the left TPA and other brain areas. This study suggests that hierarchal network structure rather than connectivity per se is important in determining phonological decoding performance. PMID- 21980022 TI - Cervical spinal trauma in children and adults: perioperative considerations. PMID- 21980020 TI - Mapping the tonotopic organization in human auditory cortex with minimally salient acoustic stimulation. AB - Despite numerous neuroimaging studies, the tonotopic organization in human auditory cortex is not yet unambiguously established. In this functional magnetic resonance imaging study, 20 subjects were presented with low-level task irrelevant tones to avoid spread of cortical activation. Data-driven analyses were employed to obtain robust tonotopic maps. Two high-frequency endpoints were situated on the caudal and rostral banks of medial Heschl's gyrus, while low frequency activation peaked on its lateral crest. Based on cortical parcellations, these 2 tonotopic progressions coincide with the primary auditory field (A1) in lateral koniocortex (Kl) and the rostral field (R) in medial koniocortex (Km), which together constitute a core region. Another gradient was found on the planum temporale. Our results show the bilateral existence of 3 tonotopic gradients in angulated orientations, which contrasts with colinear configurations that were suggested before. We argue that our results corroborate and elucidate the apparently contradictory findings in literature. PMID- 21980023 TI - Biologic and pharmacologic augmentation of rotator cuff repairs. AB - As rotator cuff repair techniques have improved, failure of the tendon to heal to the proximal humerus is less likely to occur from weak tendon-to-bone fixation. More likely causes of failure include biologic factors such as intrinsic tendon degeneration, fatty atrophy, fatty infiltration of muscle, and lack of vascularity of the tendons. High failure rates have led to the investigation of biologic augmentation to potentially enhance the healing response. Histologic studies have shown that restoration of the rotator cuff footprint during repair can help reestablish the enthesis. In animal models, growth factors and their delivery scaffolds as well as tissue engineering have shown promise in decreasing scar tissue while maintaining biomechanical strength. Platelet-rich plasma may be a safe adjuvant to rotator cuff repair, but it has not been shown to improve healing or function. Many of these strategies need to be further defined to permit understanding of, and to optimize, the biologic environment; in addition, techniques need to be refined for clinical use. PMID- 21980024 TI - The role of high tibial osteotomy in the varus knee. AB - High tibial osteotomy (HTO) is a widely performed procedure, and good results can be achieved with appropriate patient selection and precise surgical technique. Clinical indications include varus alignment of the knee associated with medial compartment arthrosis, knee instability, medial compartment overload following meniscectomy, and osteochondral defects requiring resurfacing procedures. Coronal alignment (ie, varus, valgus) and sagittal alignment (ie, tibial slope) should be thoroughly evaluated in all cases. Many techniques have been described for HTO, whether alone or in combination with other procedures (eg, anterior cruciate ligament reconstruction, meniscal transplant, cartilage resurfacing). Little direct evidence exists regarding the effectiveness of HTO alone or in combination with other procedures because of the lack of randomized controlled studies. However, it is commonly accepted that correct alignment is essential in achieving durable results. PMID- 21980025 TI - Pediatric cervical spine trauma. AB - Pediatric cervical spine injuries are rare and are associated with significant morbidity and mortality. Pediatric anatomy and physiology predispose to upper cervical spine injury and spinal cord injury without radiologic abnormality in contrast to lower cervical spine injury seen in adults. Care of pediatric patients is difficult because they have a greater head-to-body ratio than adults and may have difficulty cooperating with a history and physical examination. In evaluating a child with a suspected cervical spine injury, radiography may be supplemented with CT or MRI. Definitive management of pediatric cervical spine trauma must be adapted to the distinctive anatomy and growth potential of the patient. As with all injuries, prevention is necessary to reduce the incidence of trauma to the pediatric spine. PMID- 21980026 TI - Pilon fractures: advances in surgical management. AB - Pilon fractures are challenging to manage because of the complexity of the injury pattern and the risk of significant complications. Variables such as fracture pattern, soft-tissue injury, and preexisting patient factors can lead to unpredictable outcomes. Avoiding complications associated with the soft-tissue envelope is paramount to optimizing outcomes. In persons with soft-tissue compromise, the use of temporary external fixation and staged management is helpful in reducing further injury and complications. Evidence in support of new surgical approaches and minimally invasive techniques is incomplete. Soft-tissue management, such as negative-pressure dressings, may be helpful in preventing complications. PMID- 21980027 TI - Galeazzi fracture. AB - Galeazzi fracture is a fracture of the radial diaphysis with disruption at the distal radioulnar joint (DRUJ). Typically, the mechanism of injury is forceful axial loading and torsion of the forearm. Diagnosis is established on radiographic evaluation. Underdiagnosis is common because disruption of the ligamentous restraints of the DRUJ may be overlooked. Nonsurgical management with anatomic reduction and immobilization in a long-arm cast has been successful in children. In adults, nonsurgical treatment typically fails because of deforming forces acting on the distal radius and DRUJ. Open reduction and internal fixation is the preferred surgical option. Anatomic reduction and rigid fixation should be followed by intraoperative assessment of the DRUJ. Further intraoperative interventions are based on the reducibility and postreduction stability of the DRUJ. Misdiagnosis or inadequate management of Galeazzi fracture may result in disabling complications, such as DRUJ instability, malunion, limited forearm range of motion, chronic wrist pain, and osteoarthritis. PMID- 21980028 TI - The impact of complementary and alternative treatment modalities on the care of orthopaedic patients. AB - The use of complementary and alternative medicine is widespread and popular with the lay public. Although prevalence of use varies among specific patient populations, complementary and alternative medicine, in particular herbal remedies, are widely marketed and used by orthopaedic patients. Herbal supplements can have a negative impact on the perioperative period and may interact with conventional medicines used to manage chronic conditions. Physician patient communication often does not include the subject of alternative medicines, leading to underreporting of use. Orthopaedic surgeons should adopt methods to routinely elicit from their patients the use of complementary and alternative medicine and should monitor and counsel patients on potential side effects and drug-herb interactions. Preoperative instructions should include cessation of the use of herbal supplements. PMID- 21980030 TI - Complete genome sequence of a Chinese virulent porcine epidemic diarrhea virus strain. AB - CH/S is a virulent porcine epidemic diarrhea virus (PEDV) strain and is used as the virulent strain to evaluate the protection rates of vaccines against PEDV infection in China. Here, we report the complete genome sequence of strain CH/S, which may aid in understanding the molecular characteristics of this strain. PMID- 21980031 TI - Complete genome sequence of human adenovirus prototype 17. AB - As one of the first five human adenoviruses (HAdVs) to be sequenced, type 17 was important as a reference tool for comparative genomics of recently isolated HAdV pathogens in species D. HAdV-D17 was the first species D adenovirus to be sequenced and was deposited in GenBank in 1999. These genome data were not of high quality, and a redetermination of the same stock virus provides corrected data; among the differences are a length of 35,139 bp versus 35,100 bp in the original, and 160 mismatches to the original genome were found. Annotation of the coding sequences reveals 39 as opposed to 8, a finding which is important for phylogenomic studies. PMID- 21980032 TI - Decision making in patients with pulmonary nodules. AB - Integrating current evidence with fundamental concepts from decision analysis suggests that management of patients with pulmonary nodules should begin with estimating the pretest probability of cancer from the patient's clinical risk factors and computed tomography characteristics. Then, the consequences of treatment should be considered, by comparing the benefits of surgery if the patient has lung cancer with the potential harm if the patient does not have cancer. This analysis determines the "treatment threshold," which is the point around which the decision centers. This varies widely among patients depending on their cardiopulmonary reserve, comorbidities, and individual preferences. For patients with a very low probability of cancer, careful observation with serial computed tomography is warranted. For those with a high probability of cancer, surgical diagnosis is warranted. For patients in the intermediate range of probabilities, either computed tomography-guided fine-needle aspiration biopsy or positron emission tomography, possibly followed by computed tomography-guided fine-needle aspiration biopsy, is best. Patient preferences should be considered because the absolute difference in outcome between strategies may be small. The optimal approach to the management of patients with pulmonary nodules is evolving as technologies develop. Areas of uncertainty include quantifying the hazard of delayed diagnosis; determining the optimal duration of follow-up for ground-glass and semisolid opacities; establishing the roles of volumetric imaging, advanced bronchoscopic technologies, and limited surgical resections; and calculating the cost-effectiveness of different strategies. PMID- 21980033 TI - Long-term ambient fine particulate matter air pollution and lung cancer in a large cohort of never-smokers. AB - RATIONALE: There is compelling evidence that acute and chronic exposure to ambient fine particulate matter (PM(2.5)) air pollution increases cardiopulmonary mortality. However, the role of PM(2.5) in the etiology of lung cancer is less clear, particularly at concentrations that prevail in developed countries and in never-smokers. OBJECTIVES: This study examined the association between mean long term ambient PM(2.5) concentrations and lung cancer mortality among 188,699 lifelong never-smokers drawn from the nearly 1.2 million Cancer Prevention Study II participants enrolled by the American Cancer Society in 1982 and followed prospectively through 2008. METHODS: Mean metropolitan statistical area PM(2.5) concentrations were determined for each participant based on central monitoring data. Cox proportional hazards regression models were used to estimate multivariate adjusted hazard ratios and 95% confidence intervals for lung cancer mortality in relation to PM(2.5). MEASUREMENTS AND MAIN RESULTS: A total of 1,100 lung cancer deaths were observed during the 26-year follow-up period. Each 10 MUg/m(3) increase in PM(2.5) concentrations was associated with a 15-27% increase in lung cancer mortality. The association between PM(2.5) and lung cancer mortality was similar in men and women and across categories of attained age and educational attainment, but was stronger in those with a normal body mass index and a history of chronic lung disease at enrollment (P < 0.05). CONCLUSIONS: The present findings strengthen the evidence that ambient concentrations of PM(2.5) measured in recent decades are associated with small but measurable increases in lung cancer mortality. PMID- 21980035 TI - Possible role of the JAK/STAT pathways in the regulation of T cell-interferon related genes in systemic lupus erythematosus. AB - Changes in gene expression in CD3+ T cells associated with disease progression in systemic lupus erythematosus (SLE) patients were determined. The genes related to SLE disease-related activities were identified and their gene regulatory networks were investigated. Analyses of gene expression were performed by both DNA microarray and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The expression of certain genes including interferon (IFN) regulatory factor (IRF)-related genes, such as IFN-regulated, -related, and signature genes was increased in the active phase of SLE. Pathway network analyses suggested that these IRF-related genes are regulated through the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. JAK/STAT pathway-mediated regulation of IRF-related genes may have an important role in the disease activity of SLE. Inhibitors of JAK/STAT cascade may be useful as therapeutic agents. PMID- 21980034 TI - Absence of integrin alphavbeta3 enhances vascular leak in mice by inhibiting endothelial cortical actin formation. AB - RATIONALE: Sepsis and acute lung injury (ALI) have devastatingly high mortality rates. Both are associated with increased vascular leak, a process regulated by complex molecular mechanisms. OBJECTIVES: We hypothesized that integrin alphavbeta3 could be an important determinant of vascular leak and endothelial permeability in sepsis and ALI. METHODS: beta3 subunit knockout mice were tested for lung vascular leak after endotracheal LPS, and systemic vascular leak and mortality after intraperitoneal LPS and cecal ligation and puncture. Possible contributory effects of beta3 deficiency in platelets and other hematopoietic cells were excluded by bone marrow reconstitution experiments. Endothelial cells treated with alphavbeta3 antibodies were evaluated for sphingosine-1 phosphate (S1P)-mediated alterations in barrier function, cytoskeletal arrangement, and integrin localization. MEASUREMENTS AND MAIN RESULTS: beta3 knockout mice had increased vascular leak and pulmonary edema formation after endotracheal LPS, and increased vascular leak and mortality after intraperitoneal LPS and cecal ligation and puncture. In endothelial cells, alphavbeta3 antibodies inhibited barrier-enhancing and cortical actin responses to S1P. Furthermore, S1P induced translocation of alphavbeta3 from discrete focal adhesions to cortically distributed sites through Gi- and Rac1-mediated pathways. Cortical alphavbeta3 localization after S1P was decreased by alphavbeta3 antibodies, suggesting that ligation of the alphavbeta3 with its extracellular matrix ligands is required to stabilize cortical alphavbeta3 focal adhesions. CONCLUSIONS: Our studies identify a novel mechanism by which alphavbeta3 mitigates increased vascular leak, a pathophysiologic function central to sepsis and ALI. These studies suggest that drugs designed to block alphavbeta3 may have the unexpected side effect of intensifying sepsis- and ALI-associated vascular endothelial leak. PMID- 21980036 TI - Differential splicing generates new transmembrane receptor and extracellular matrix-related targets for antibody-based therapy of cancer. AB - Alternative splicing has been shown to be deregulated in cancer and a link to growth stimulation has been established. Here we describe transmembrane and extracellular matrix-related targets generated by alternative splicing with a restricted pattern of expression in normal tissues and a deregulated pattern of expression in cancer as possible targets for therapeutic intervention with antibody-related agents. We focus on isoforms of transmembrane and extracellular matrix proteins, such as CD44, Claudin 18, L1 cell adhesion molecule and epithelial cellular adhesion molecule, fibronectin, tenascin, osteopontin and versican as well as transmembrane tyrosine kinases, such as fibroblast growth factor receptors, epidermal growth factor receptor and receptor d'origin nantais. PMID- 21980037 TI - Restoration of senescence in breast and ovarian cancer cells following the transfer of the YAC carrying SEN6A gene located at 6q16.3. AB - We previously located a senescence gene locus (SEN6A), at chromosome 6q14-21 by a functional strategy using chromosome transfer into immortal ovarian tumor cells. To further elucidate the SEN6A locus, intact chromosome 6 or 6q was transferred into rat ovarian tumor cells and a panel of immortal revertant clones of senescent cells was generated. The panel of independent colonies as well as mixed populations of revertant cells was analyzed for the presence or absence of chromosome 6 specific markers. These investigations led to the identification of a fine deletion of approximately 1cM at chromosomal interval 6q16.3. A contiguous stretch containing five yeast artificial chromosome (YAC) clones was constructed across the deleted region. The non-chimeric YAC clones were retrofitted and transferred into mouse A9 cells by spheroplast fusion to generate YAC/A9 hybrids. YAC DNA present in YAC/A9 hybrids was subsequently transferred by microcell fusion into immortal tumor cells, and the hybrid cells were characterized for their senescence phenotype. Using this functional strategy, the transfer of YAC clone 966b10 was shown to restore senescence in both rat and human ovarian and breast tumor cells. Our results demonstrate that the SEN6A gene is carried on a 1 Mb YAC, 966b10, which maps at 6q16.3. PMID- 21980038 TI - Aberrant expression of chromogranin A, miR-146a, and miR-146b-5p in prostate structures with focally disrupted basal cell layers: an early sign of invasion and hormone-refractory cancer? AB - Our recent studies have suggested that prostate tumor invasion is triggered by autoimmunoreactions induced focal basal cell layer disruptions (FBCLD) that selectively favor monoclonal proliferation of the overlying progenitors or of a biologically more aggressive cell clone. As circulating chromogranin-A (CgA) levels are found to correlate with tumor progression and the status of hormone refractoriness, our current study attempted to assess whether CgA-positive cells would be preferentially distributed in epithelial structures with FBCLD. Paraffin embedded specimens from 50 patients with organ-confined prostate cancer were subjected to double immunohistochemical analysis with monoclonal antibodies to basal cells and CgA. From each case, 3-5 randomly selected fields were digitally photographed and the photos were magnified 400% and the numbers of CgA-positive cells in epithelial structures with non-disrupted, focally disrupted, and lost basal cell layer were separately counted. The averaged number of cell for each category was statistically compared with the Pearson's Chi-square test. In addition, morphologically similar structures with and without CgA-positive cell clusters were microdissected from four selected cases and subjected to a comparison of differential micro-RNA expression levels. Our study revealed that, although isolated CgA-positive cells were seen in both the basal cell layer and the luminal cell population in all cases, only 8 cases (16%) harbored large clusters of CgA-positive cells that were concentrated in a given area, in which all or nearly all cells appeared to share a similar morphological and immunohistochemical profile. Microdissected epithelial structures with CgA positive cell clusters exhibited a more than 5- and 7-fold lower expression of miR-146a and miR-146b-5p than their CgA-negative counterparts. As focal basal cell layer disruptions and the reduction or loss of miR-146a and miR-146b-5p has been documented to correlate with prostate tumor invasion and hormone refractoriness, our findings suggest that aberrant CgA expression in epithelial structures with FBCLD may represent an early sign of these events. PMID- 21980039 TI - Timing of ganciclovir administration in glioma gene therapy using HSVtk gene transduced mesenchymal stem cells. AB - BACKGROUND: An established C6 glioma was successfully treated with intratumoral injection of mesenchymal stem cells transduced with HSVtk gene (MSCtk) and systemic administration of ganciclovir (GCV). The best timing of GCV administration after the MSCtk implantation was studied. MATERIALS AND METHODS: GCV administration was started from 2 days before and 1, 3 and 7 days after the MSCtk administration under both in vitro and in vivo conditions. RESULTS: The C6 cells were completely eradicated in vitro when GCV administration was started from day -2, 1, and 3. Animals with intracranial tumor survived longer when GCV was administered earlier after MSCtk administration. This may, mainly, reflect the difference in the MSCtk/C6 ratio at the time of GCV administration because this ratio drastically decreases during the delay of GCV administration. CONCLUSION: When using a slowly growing vector cell as MSCtk, GCV should be administered soon after MSCtk implantation. PMID- 21980040 TI - Association of Alpha B-Crystallin (CRYAB) genotypes with breast cancer susceptibility in Taiwan. AB - AIM: Alpha B-Crystallin (CRYAB) is purported to be a metastasis suppressor protein, and lack or lower CRYAB expression is a prognostic biomarker for several types of cancer, such as that of the prostate and head and neck. However, the association of genomic variation of CRYAB and breast cancer is not well studied. The aim of this study was to evaluate the association of polymorphic genotypes of CRYAB with breast cancer within a Taiwanese population. PATIENTS AND METHODS: In this hospital-based study, 1232 patients with breast cancer and an equal number of healthy controls in central Taiwan were genotyped via polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) and the association of CRYAB A-1215G (rs2228387), C-802G (rs14133) and intron 2 (rs2070894) polymorphisms with breast cancer risk in a central Taiwanese population was investigated. RESULTS: Those individuals with CRYAB C-802G CG and GG genotypes had 1.50- and 2.22-fold risk for breast cancer than those with the CC genotype. As for the A-1215G and intron 2 polymorphisms, there was no significant association of the genotype with breast cancer risk. In allelic frequency analysis, the G allele CRYAB C-802G conferred a significantly (p=5.63*10(-10)) increased risk of breast cancer. Our results provide evidence that the G allele of CRYAB C-802G is correlated with breast cancer risk and this polymorphism may be a useful marker for early detection of breast cancer in clinical practice. PMID- 21980041 TI - Gemcitabine and platinum pathway pharmacogenetics in Asian breast cancer patients. AB - BACKGROUND/AIM: Gemcitabine/carboplatin is efficacious in breast cancer but results in significant hematologic toxicities. We employed a multi-gene approach to identify variants to predict its toxicities. PATIENTS AND METHODS: Twenty-six gemcitabine and platinum-based DNA repair pathway polymorphisms were correlated with gemcitabine pharmacokinetics, hematologic toxicities, response and survival in 41 Asian breast cancer patients receiving gemcitabine/carboplatin. RESULTS: The combined effects of solute carrier family (SLC)28A1+1528C>T and thymidylate synthetase (TYMS)+1494del6 significantly influenced hematologic toxicities: 89% of patients who possessed either SLC28A1+1528TT or TYMS+1494ins6/ins6 (n=9) developed grade 4 thrombocytopenia, versus 14% with neither genotype (n=29; p<0.001). In concordance, all patients who possessed either genotype developed grade 3/4 neutropenia, compared to 38% with neither genotype (p=0.001). None of the other genetic variants analyzed correlated with drug pharmacokinetics and pharmacodynamics. CONCLUSION: Approximately one-quarter of our Asian cohort carried SLC28A1+1528TT or TYMS+1494ins6/ins6, which are associated with increased myelotoxicity from gemcitabine/carboplatin. This has potential utility in treatment selection and genotype-based dosing strategies. PMID- 21980043 TI - Identification of international circulating lineages of meticillin-resistant Staphylococcus aureus in the north of Spain and their glycopeptide and linezolid susceptibility. PMID- 21980044 TI - Insertion sequence evolutionary patterns highlight convergent genetic inactivations and recent genomic island acquisitions among epidemic Burkholderia cenocepacia. AB - The Burkholderia cenocepacia B&B clone was found previously to be responsible for an epidemic outbreak within an intensive care unit in France. This clone belongs to the ST32 clonal complex, which is one of the most prevalent among French cystic fibrosis patients and is known to be related to the highly virulent ET12 clonal complex. Genomic repartition biases of insertion sequences (ISs) were investigated to improve our understanding of the evolutionary events leading to B. cenocepacia diversification and the emergence of such epidemic lineages. IS were used for tracking convergent genetic inactivations and recent DNA acquisitions. B. cenocepacia IS families and subgroups were compared in terms of genetic diversity and genomic architecture using fully sequenced genomes, PCR screening and DNA blot analysis. These analyses revealed several features shared by the B&B and ET12 epidemic clones. IS elements showed a frequent localization on genomic islands (GI) and indicated convergent evolution towards inactivation of certain loci. The IS407 subgroup of the IS3 family was identified as a good indicator of recently acquired GIs in clone ET12. Several IS407 elements showed strain-specific or clonal complex-specific localizations. IS407 DNA probing of a DNA library built from the B. cenocepacia B&B epidemic clone led to the identification of a recently acquired IS407-tagged GI likely to be conjugative and integrative. The B&B clone showed significant differences in its IS architecture from that of ST32 strains isolated from Czech cystic fibrosis patients. PMID- 21980045 TI - Lenalidomide in MDS: 4th time's a charm. PMID- 21980046 TI - Guilt by association. PMID- 21980047 TI - Mutant JAK3 FERMents ATLL. PMID- 21980048 TI - A platelet transcriptome revolution. PMID- 21980049 TI - HLA matching of CB: it's complicated. PMID- 21980050 TI - JCOG Radiation Therapy Study Group: history and achievements. AB - The Radiation Therapy Study Group (RTSG) of the Japan Clinical Oncology Group (JCOG) was established in 2003. The missions of this group are to develop new standards of care with innovative, advanced technology radiation therapy, both for single- and multi-modality cancer treatment, and to improve radiation therapy quality and outcomes of JCOG trials conducted by other organ-oriented groups. In 2004, the first RTSG trial, a Phase II study of stereotactic body radiation therapy for Stage IA non-small cell lung cancer (JCOG 0403), was initiated. Four other trials are currently open for accrual. JCOG 0702 is a Phase I study of stereotactic body radiation therapy in patients with T2N0M0 non-small cell lung cancer. JCOG 0701 is a Phase III study comparing accelerated fractionation with conventional fractionation radiation therapy for T1-2N0M0 glottic cancer. JCOG 0906 is a multicenter safety trial of hypofractionated radiation therapy after breast-conserving surgery in patients with margin-negative invasive breast cancer. JCOG 1015 is a Phase II study of intensity-modulated radiation therapy with chemotherapy for loco-regionally advanced nasopharyngeal cancer. Other RTSG activities include a medical physics working group responsible for dosimetry audits; a genetic analysis working group involved in accompanying research to analyze single-nucleotide polymorphisms to identify predictors of radiation toxicities; a working group that has developed atlases of clinical target volumes for uterine cervical cancer; and participation in the Harmonisation Group to promote global harmonization of radiotherapy and radiotherapy quality assurance among trial groups. Further efforts to improve radiation therapy quality and outcomes of cancer treatment are necessary. PMID- 21980051 TI - Past and present achievements, and future direction of the Gastrointestinal Oncology Study Group (GIOSG), a Division of Japan Clinical Oncology Group (JCOG). AB - Initially, Gastrointestinal Study Group in Japan Clinical Oncology Group (GIOSG/JCOG) focused on gastric cancer. In 1980s, fluoropyrimidine, cisplatin and mitomycin C were key drugs. A randomized Phase II trial (JCOG8501) comparing futrafur plus mitomycin C and uracil plus futrafur and mitomycin C showed a higher response rate of uracil plus futrafur and mitomycin C than futrafur plus mitomycin C. From the results of two Phase II trials of etoposide, adriamycin and cisplatin, and cisplatin plus 5-fluorouracil, uracil plus futrafur and mitomycin C and cisplatin plus 5-fluorouracil were adopted for the test arms of the Phase III trial (JCOG9205) comparing with continuous infusion of 5-fluorouracil as a control arm. Neither cisplatin plus 5-fluorouracil nor uracil plus futrafur and mitomycin C showed a survival benefit over continuous infusion of 5-fluorouracil. In late 1990s, new agents, irinotecan and S-1, were developed for gastric cancer in Japan. GIOSG conducted a Phase III trial (JCOG9912) investigating superiority of irinotecan plus cisplatin and non-inferiority of monotherapy with S-1 compared with continuous infusion of 5-fluorouracil, and S-1 succeeded in showing non inferiority. Then, SPIRITS trial showed a survival benefit of S-1 plus cisplatin over S-1, resulting in the establishment of a standard care for advanced gastric cancer in Japan. GIOSG have merged with Gastric Cancer Study Group as the Stomach Cancer Study Group (SCSG) from 2011. Recent progress in the development of new drugs has been remarkable. From the point of the roles shared with many other study groups for clinical trials, including registration trials of new drugs conducted by pharmaceutical companies, SCSG should recognize its role and conduct clinical trials with high quality for establishing new standard treatment. PMID- 21980052 TI - Metastatic adrenocortical carcinoma presenting simultaneously with Cushing's and Conn's syndromes: a case report. AB - We report the first case of adrenocortical carcinoma secreting cortisol (Cushing's syndrome) and aldosterone (Conn's syndrome) with extensive distant metastasis at the time of diagnosis. A 72-year-old male with exertional dyspnea sought evaluation at our institution. The pattern of tumor spread (lung, pleura, bone and adrenal gland) and respiratory symptoms secondary to the tumor led clinicians to diagnose the primary tumor site as lung cancer and the adrenal mass as a metastatic site. However, endocrinologic studies and a biopsy revealed the primary site to be adrenocortical carcinoma. After histopathologic confirmation, the patient was treated with palliative chemotherapy, including mitotane, cisplatin, etoposide and doxorubicin. The patient died on the 14th day after chemotherapy of rapidly progressive and unexpected pneumonia, which was thought to be an opportunistic infection secondary to Cushing's syndrome. Our case suggests that a thorough endocrinologic investigation is important in patients with an adrenal mass and clinicians should be aware that patients with adrenocortical carcinoma and Cushing's syndrome are susceptible to infections and need to be observed carefully for the possible development of unrecognized opportunistic infections. PMID- 21980053 TI - S-1 monotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck after progression on platinum-based chemotherapy. AB - OBJECTIVE: Platinum compounds play pivotal roles in treatment for squamous cell carcinoma of the head and neck. The objective was to evaluate the efficacy of S-1 monotherapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after failure of platinum-based chemotherapy. METHODS: We retrospectively analyzed 39 consecutive patients with recurrent or metastatic squamous cell carcinoma of the head and neck who received S-1 monotherapy after failure of platinum-based chemotherapy or chemoradiotherapy at the Shizuoka Cancer Center between August 2003 and October 2010. S-1 was given orally twice daily (80 mg/m(2)/day) for 28 days followed by a 14-day rest. RESULTS: The median follow-up period in survivors was 31.5 months. Among 38 patients with measurable lesions, 9 (24%) showed partial response and 15 (39%) showed stable disease. The median progression-free survival was 4.9 months and the median overall survival was 13.2 months. The median progression-free survival for oropharyngeal cancer (n= 7) was significantly longer than for other cancers (n = 32) (14.9 vs. 4.7 months, P= 0.035). The response rate in patients with a recurrence-free interval since the last platinum administration >6.0 months was significantly better than with a recurrence-free interval <6.0 months (40 vs. 13%, P= 0.0102). Recurrence free interval >6.0 months also showed a significantly better progression-free survival (6.0 vs. 2.6 months, P= 0.045). The frequency of Grade 3/4 toxicities was less than 10%. CONCLUSIONS: S-1 monotherapy shows promising signs of efficacy and tolerability in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after failure of platinum-based chemotherapy in this retrospective cohort and warrants further investigation in this population. PMID- 21980054 TI - Involvement of creatine kinase B in cigarette smoke-induced bronchial epithelial cell senescence. AB - Cigarette smoke induces damage to proteins and organelles by oxidative stress, resulting in accelerated epithelial cell senescence in the lung, which is implicated in chronic obstructive pulmonary disease (COPD) pathogenesis. Although the detailed molecular mechanisms are not fully understood, cellular energy status is one of the most crucial determinants for cell senescence. Creatine kinase (CK) is a constitutive enzyme, playing regulatory roles in energy homeostasis of cells. Among two isozymes, brain-type CK (CKB) is the predominant CK in lung tissue. In this study, we investigated the role of CKB in cigarette smoke extract (CSE)-induced cellular senescence in human bronchial epithelial cells (HBECs). Primary HBECs and Beas2B cells were used. Protein carbonylation was evaluated as a marker of oxidative protein damage. Cellular senescence was evaluated by senescence-associated beta-galactosidase staining. CKB inhibition was examined by small interfering RNA and cyclocreatine. Secretion of IL-8, a hallmark of senescence-associated secretary phenotype, was measured by ELISA. CKB expression levels were reduced in HBECs from patients with COPD compared with that of HBECs from nonsmokers. CSE induced carbonylation of CKB and subsequently decreased CKB protein levels, which was reversed by a proteasome inhibitor. CKB inhibition alone induced cell senescence, and further enhanced CSE-induced cell senescence and IL-8 secretion. CSE-induced oxidation of CKB is a trigger for proteasomal degradation. Concomitant loss of enzymatic activity regulating energy homeostasis may lead to the acceleration of bronchial epithelial cell senescence, which is implicated in the pathogenesis of COPD. PMID- 21980055 TI - Acute hyperglycemic exacerbation of lung ischemia-reperfusion injury is mediated by receptor for advanced glycation end-products signaling. AB - The effects of acute hyperglycemia on lung ischemia-reperfusion (IR) injury and the role of receptor for advanced glycation end-products (RAGE) signaling in this process are unknown. The objective of this study was twofold: (1) evaluate the impact of acute hyperglycemia on lung IR injury; and (2) determine if RAGE signaling is a mechanism of hyperglycemia-enhanced IR injury. We hypothesized that acute hyperglycemia worsens lung IR injury through a RAGE signaling mechanism. C57BL/6 wild-type (WT) and RAGE knockout (RAGE (-/-)) mice underwent sham thoracotomy or lung IR (1-h left hilar occlusion and 2-h reperfusion). Acute hyperglycemia was established by dextrose injection 30 minutes before ischemia. Lung injury was assessed by measuring lung function, cytokine expression in bronchoalveolar lavage fluid, leukocyte infiltration, and microvascular permeability via Evans blue dye. Mean blood glucose levels doubled in hyperglycemic mice 30 minutes after dextrose injection. Compared with IR in normoglycemic mice, IR in hyperglycemic mice significantly enhanced lung dysfunction, cytokine expression (TNF-alpha, keratinocyte chemoattractant, IL-6, monocyte chemotactic protein-1, regulated upon activation, normal T cell expressed and secreted), leukocyte infiltration, and microvascular permeability. Lung injury and dysfunction after IR were attenuated in normoglycemic RAGE (-/-) mice, and hyperglycemia failed to exacerbate IR injury in RAGE (-/-) mice. Thus, this study demonstrates that acute hyperglycemia exacerbates lung IR injury, whereas RAGE deficiency attenuates IR injury and also prevents exacerbation of IR injury in an acute hyperglycemic setting. These results suggest that hyperglycemia-enhanced lung IR injury is mediated, at least in part, by RAGE signaling, and identifies RAGE as a potential, novel therapeutic target to prevent post-transplant lung IR injury. PMID- 21980056 TI - Case studies of the spatial heterogeneity of DNA viruses in the cystic fibrosis lung. AB - Microbial communities in the lungs of patients with cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) have been shown to be spatially heterogeneous. Viral communities may also vary spatially, leading to localized viral populations and infections. Here, we characterized viral communities from multiple areas of the lungs of two patients with late-stage CF using metagenomics, that is, the explanted lungs from a transplant patient and lungs acquired postmortem. All regions harbored eukaryotic viruses that may infect the human host, notably herpesviruses, anelloviruses, and papillomaviruses. In the highly diseased apical lobes of explant lungs, viral diversity was extremely low, and only eukaryotic viruses were present. The absence of phage suggests that CF associated microbial biofilms may escape top-down controls by phage predation. The phages present in other lobes of explant lungs and in all lobes of postmortem lungs comprised distinct communities, and encoded genes for clinically important microbial phenotypes, including small colony variants and antibiotic resistance. Based on the these observations, we postulate that viral communities in CF lungs are spatially distinct and contribute to CF pathology by augmenting the metabolic potential of resident microbes, as well as by directly damaging lung tissue via carcinomas and herpesviral outbreaks. PMID- 21980057 TI - The polypyrimidine tract binding protein regulates desaturase alternative splicing and PUFA composition. AB - The Delta6 desaturase, encoded by FADS2, plays a crucial role in omega-3 and omega-6 fatty acid synthesis. These fatty acids are essential components of the central nervous system, and they act as precursors for eicosanoid signaling molecules and as direct modulators of gene expression. The polypyrimidine tract binding protein (PTB or hnRNP I) is a splicing factor that regulates alternative pre-mRNA splicing. Here, PTB is shown to bind an exonic splicing silencer element and repress alternative splicing of FADS2 into FADS2 AT1. PTB and FADS2AT1 were inversely correlated in neonatal baboon tissues, implicating PTB as a major regulator of tissue-specific FADS2 splicing. In HepG2 cells, PTB knockdown modulated alternative splicing of FADS2, as well as FADS3, a putative desaturase of unknown function. Omega-3 fatty acids decreased by nearly one half relative to omega-6 fatty acids in PTB knockdown cells compared with controls, with a particularly strong decrease in eicosapentaenoic acid (EPA) concentration and its ratio to arachidonic acid (ARA). This is a rare demonstration of a mechanism specifically altering the cellular omega-3 to omega-6 fatty acid ratio without any change in diet/media. These findings reveal a novel role for PTB, regulating availability of membrane components and eicosanoid precursors for cell signaling. PMID- 21980058 TI - Acute effects of salmeterol and fluticasone propionate alone and in combination on airway blood flow in patients with asthma. AB - BACKGROUND: The airway contains airway smooth muscle and airway vascular smooth muscle. The acute effects of inhaled long-acting beta(2)-adrenergic agonists (LABAs) alone, or in combination with an inhaled glucocorticoid (ICS), on airway smooth muscle tone in asthma are known; however, to the best of our knowledge, their effect on airway vascular smooth muscle tone has not been investigated previously. The objective of this study was to investigate the immediate effects of a LABA and an ICS alone and in combination on airway blood flow (Qaw) as an index of airway vascular smooth muscle tone in patients with stable asthma. METHODS: Fourteen subjects with moderate asthma inhaled single doses of salmeterol (50 MUg), fluticasone propionate (250 MUg), salmeterol/fluticasone propionate (50/250 MUg), or placebo; Qaw was measured before and serially for 240 min after drug administration. RESULTS: Mean Qaw increased after salmeterol and salmeterol/fluticasone propionate, with peaks at 60 min of 34% and 40%, respectively, and returned to baseline by 240 min after inhalation. Fluticasone propionate alone caused a transient decrease in mean Qaw. The maximal changes in Qaw, which occurred at different times, were 60% for salmeterol, 67% for salmeterol/fluticasone propionate, and -19% for fluticasone propionate (P < .05 vs placebo for all). CONCLUSIONS: The LABA salmeterol has an acute vasodilator action on the airway of subjects with stable asthma. The addition of fluticasone propionate, which by itself causes vasoconstriction, does not attenuate the salmeterol-induced vasodilation, suggesting that fluticasone propionate potentiates the vasodilator effect of salmeterol. The vasodilation could be of clinical benefit by promoting the vascular clearance of inflammatory mediators including spasmogens from the airway. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01231230; URL: www.clinicaltrials.gov. PMID- 21980059 TI - Meta-analysis of guided bronchoscopy for the evaluation of the pulmonary nodule. AB - BACKGROUND: The detection of pulmonary nodules (PNs) is likely to increase, especially with the release of the National Lung Screen Trials. When tissue diagnosis is desired, transthoracic needle aspiration (TTNA) is recommended. Several guided-bronchoscopy technologies have been developed to improve the yield of transbronchial biopsy for PN diagnosis: electromagnetic navigation bronchoscopy (ENB), virtual bronchoscopy (VB), radial endobronchial ultrasound (R EBUS), ultrathin bronchoscope, and guide sheath. We undertook this meta-analysis to determine the overall diagnostic yield of guided bronchoscopy using one or a combination of the modalities described here. METHODS: We performed a MEDLINE search using "bronchoscopy" and "solitary pulmonary nodule." Studies evaluating the diagnostic yield of ENB, VB, R-EBUS, ultrathin bronchoscope, and/or guide sheath for peripheral nodules were included. The overall diagnostic yield and yield based on size were extracted. Adverse events, if reported, were recorded. Meta-analysis techniques incorporating inverse variance weighting and a random effects meta-analysis approach were used. RESULTS: A total of 3,052 lesions from 39 studies were included. The pooled diagnostic yield was 70%, which is higher than the yield for traditional transbronchial biopsy. The yield increased as the lesion size increased. The pneumothorax rate was 1.5%, which is significantly smaller than that reported for TTNA. CONCLUSION: This meta-analysis shows that the diagnostic yield of guided bronchoscopic techniques is better than that of traditional transbronchial biopsy. Although the yield remains lower than that of TTNA, the procedural risk is lower. Guided bronchoscopy may be an alternative or be complementary to TTNA for tissue sampling of PN, but further study is needed to determine its role in the evaluation of peripheral pulmonary lesions. PMID- 21980060 TI - Performance of confirmatory interferon-gamma release assays in school TB outbreaks. AB - BACKGROUND: Interferon-gamma release assays (IGRAs) have been incorporated into several national guidelines for latent TB infection (LTBI) diagnosis. However, their optimal application is still controversial and evolving. The aim of this study is to evaluate the performance of confirmatory IGRAs in addition to tuberculin skin tests (TSTs) in high school students with TST-positive (TST+) results who have had contact with another student who had TB (referred to in this article as "contacts") in TB outbreaks in a high BCG-vaccinated population. METHODS: We conducted a retrospective observational study of contacts in five school TB outbreaks in South Korea. The progression rates of TB within 2 years were compared among the groups based on the results of TSTs and QuantiFERON-TB gold assays (QFT-Gs). RESULTS: Among 1,826 contacts, 21 (1.2%) developed active TB. Of the untreated groups, the rate of progression to TB was higher in the group with TST-positive (TST+) results (6.1%, six of 99) than in that with TST negative (TST-) results (0.6%, 10 of 1,556; P < .001). Among TST+ contacts, the rate of progression to TB was higher in the group with QFT-G-positive (QFT-G+) results (18.75%, six of 32) than that with QFT-G-negative (QFT-G(-)) results (0%, 0 of 67; P = .001). None of the 67 contacts with TST+/QFT-G(-) results progressed to active TB. CONCLUSIONS: The addition of a confirmatory IGRA for TST+ contacts could effectively focus the targeting of LTBI treatment to fewer contacts in an intermediate-incidence setting in a high BCG-vaccinated population. PMID- 21980061 TI - Obesity-associated asthma in children: a distinct entity. AB - BACKGROUND: Obesity-associated asthma has been proposed to be a distinct entity, differing in immune pathogenesis from atopic asthma. Both obesity-mediated inflammation and increase in adiposity are potential mechanistic factors that are poorly defined among children. We hypothesized that pediatric obesity-associated asthma would be characterized by T helper (Th) 1, rather than the Th2 polarization associated with atopic asthma. Moreover, we speculated that Th1 biomarkers and anthropometric measures would correlate with pulmonary function tests (PFTs) in obese asthmatic children. METHODS: We recruited 120 children, with 30 in each of the four study groups: obese asthmatic children, nonobese asthmatic children, obese nonasthmatic children, and nonobese nonasthmatic children. All children underwent pulmonary function testing. Blood was collected for measurement of serum cytokines. T-cell responses to mitogen, phorbol 12 myristate 13-acetate (PMA), or antigens tetanus toxoid or Dermatophagoides farinae were obtained by flow cytometric analysis of intracellular cytokine staining for interferon-gamma (IFN-gamma) (Th1) or IL-4 (Th2) within the CD4 population. RESULTS: Obese asthmatic children had significantly higher Th1 responses to PMA (P < .01) and tetanus toxoid (P < .05) and lower Th2 responses to PMA (P < .05) and D farinae (P < .01) compared with nonobese asthmatic children. Th-cell patterns did not differ between obese asthmatic children and obese nonasthmatic children. Obese asthmatic children had lower FEV(1)/FVC (P < .01) and residual volume/total lung capacity ratios (P < .005) compared with the other study groups, which negatively correlated with serum interferon-inducible protein 10 and IFN-gamma levels, respectively. PFTs, however, did not correlate with BMI z score or waist to hip ratio. CONCLUSIONS: We found that pediatric obesity-associated asthma differed from atopic asthma and was characterized by Th1 polarization. The altered immune environment inversely correlated with PFTs in obese asthmatic children. PMID- 21980063 TI - Control of MRSA in intensive care units. PMID- 21980064 TI - Coroners' verdicts and suicide statistics in England and Wales. PMID- 21980062 TI - Screening, isolation, and decolonisation strategies in the control of meticillin resistant Staphylococcus aureus in intensive care units: cost effectiveness evaluation. AB - OBJECTIVE: To assess the cost effectiveness of screening, isolation, and decolonisation strategies in the control of meticillin resistant Staphylococcus aureus (MRSA) in intensive care units. DESIGN: Economic evaluation based on a dynamic transmission model. SETTING: England and Wales. Population Theoretical population of patients on an intensive care unit. MAIN OUTCOME MEASURES: Infections, deaths, costs, quality adjusted life years (QALYs), incremental cost effectiveness ratios for alternative strategies, and net monetary benefits. RESULTS: All decolonisation strategies improved health outcomes and reduced costs. Although universal decolonisation (regardless of MRSA status) was the most cost effective in the short term, strategies using screening to target MRSA carriers may be preferred owing to the reduced risk of selecting for resistance. Among such targeted strategies, universal admission and weekly screening with polymerase chain reaction coupled with decolonisation using nasal mupirocin was the most cost effective. This finding was robust to the size of intensive care units, prevalence of MRSA on admission, proportion of patients classified as high risk, and precise value of willingness to pay for health benefits. All strategies using isolation but not decolonisation improved health outcomes but costs were increased. When the prevalence of MRSA on admission to the intensive care unit was 5% and the willingness to pay per QALY gained was between L20,000 (?23,000; $32,000) and L30,000, the best such strategy was to isolate only those patients at high risk of carrying MRSA (either pre-emptively or after identification by admission and weekly screening for MRSA using chromogenic agar). Universal admission and weekly screening using polymerase chain reaction based detection of MRSA coupled with isolation was unlikely to be cost effective unless prevalence was high (10% of patients colonised with MRSA on admission). CONCLUSIONS: MRSA control strategies that use decolonisation are likely to be cost saving in an intensive care unit setting provided resistance is lacking, and combining universal screening using polymerase chain reaction with decolonisation is likely to represent good value for money if untargeted decolonisation is considered unacceptable. In intensive care units where decolonisation is not implemented, evidence is insufficient to support universal screening for MRSA outside high prevalence settings. PMID- 21980065 TI - Ethical dilemmas in antibiotic treatment. AB - Patients with moderate to severe infections are given less than maximum empirical antibiotic treatment in order to reduce the rise in resistance. This practice involves two ethical dilemmas: whether the danger to a present patient should be increased (even if by a small degree) to benefit future, unidentified patients; and whether this should be done without the consent of the patient, disregarding the patient's autonomy. We argue that future patients have a right to come to no harm. Future patients being unidentified, practitioners of medicine have a duty to protect their rights and weigh them against the rights of the present patient. A decision on the collective (guidelines, decision support systems) is a convenient way to do that. Using a temporal discount rate to show that the life of present patients has pre-eminence, to some degree, over future patients does not solve the immediacy of the plight facing a present, identified patient with a very severe infection. We think there are good grounds to take into less account considerations of future resistance for such a patient, or in a formal analysis, to make the ratio of benefits to the present versus future patients dependent on the severity of disease of the present patient. None of these solve the problem of patients' autonomy. We see no other way but to argue that the right of future patients to come to less harm outweighs the right of the present patient to share in decisions on antibiotic treatment. PMID- 21980066 TI - Antifungal use influences Candida species distribution and susceptibility in the intensive care unit. AB - OBJECTIVES: Antifungal prescription practices have changed over the last decade, and the impact of these changes is unclear. Our objective here was to evaluate the effect of antifungal drug use on the distribution and drug susceptibility of Candida spp. in a French intensive care unit (ICU). METHODS: Antifungal drug use was measured as the number of defined daily doses per 1000 hospital days (DDDs/1000HD). The distribution of Candida spp. over a 6 year period (2004-09) and the MICs of antifungal drugs over 2007-09 were determined. Statistical analyses were performed to assess relationships between antifungal drug use, Candida spp. distribution and MIC changes over time. RESULTS: Of 26,450 samples from 3391 patients, 1511 were positive for Candida spp. Candida albicans predominated (52.5%), followed by Candida glabrata (16.6%) and Candida parapsilosis (7.5%). C. parapsilosis increased significantly, from 5.7% in 2004 to 12.5% in 2009 (P = 0.0005). Caspofungin use increased significantly between 2004 (17.9 DDDs/1000HD) and 2009 (69.9 DDDs/1000HD) (P < 0.0001). Between 2007 and 2009, the increase in caspofungin use correlated significantly with the increase in caspofungin MICs displayed by C. parapsilosis (P < 0.0001) and C. glabrata (P = 0.03). Amphotericin B consumption changed over time and correlated with an increase in amphotericin B MICs for C. albicans (P = 0.0002) and C. glabrata (P = 0.0005). Significant declines occurred in both fluconazole use (P < 0.0001) and fluconazole MICs of C. albicans (P < 0.001) CONCLUSIONS: Antifungal drug use in the ICU is associated with major changes in the distribution and drug susceptibility of Candida spp. PMID- 21980067 TI - Plasmid typing and genetic context of AmpC beta-lactamases in Enterobacteriaceae lacking inducible chromosomal ampC genes: findings from a Spanish hospital 1999 2007. AB - OBJECTIVES: To gain insights into ampC transmission between bacterial strains. METHODS: We examined the genetic context of 117 acquired ampC genes from 27119 Enterobacteriaceae collected between 1999 and 2007. Plasmid analysis was carried out by PCR-based replicon or relaxase typing, S1-PFGE and Southern hybridization. I-CeuI/PFGE was used for isolates not characterized by plasmid analysis. PCR reactions were used to map the genetic organization of the ampC genes. RESULTS: Among the isolates studied, 81.2% of ampC genes were located on plasmids of known Inc/MOB groups, 7.7% were chromosomally located and 11.1% were not determined. A/C, I1 and K were the most commonly found replicons in plasmids carrying bla(CMY 2), while L/M replicons were associated with bla(DHA-1). bla(ACC-1) was linked to I1 and MOB(F11) plasmids; bla(CMY-27) was associated with IncF and MOB(P12) plasmids; the plasmid carrying bla(CMY-25) could not be typed, and bla(CMY-40) was chromosomally located. All 87 isolates carrying bla(CMY-2), bla(CMY-4), bla(CMY-25), bla(CMY-27), bla(CMY-40) or bla(ACC-1) displayed the transposon-like structures ISEcp1/DeltaISEcp1-bla(CMY)-blc-sugE or DeltaISEcp1-bla(ACC-1)-gdha. The most prevalent structure in bla(DHA-1) (93.3% of cases) was identical to that described in the Klebsiella pneumoniae pTN60013 plasmid. Remarkably, in three isolates containing chromosomal bla(CMY-2), this gene was mobilized by conjugation. CONCLUSIONS: Although plasmids are the main cause of the rapid dissemination of ampC genes among bacteria, we need to be aware that other mobile genetic elements such as integrative and conjugative elements (ICEs) can be involved in the mobilization of these genes. PMID- 21980068 TI - CNS infections caused by Mycobacterium abscessus complex: clinical features and antimicrobial susceptibilities of isolates. AB - OBJECTIVES: CNS infections caused by non-tuberculous mycobacteria (NTM) are rare and only three cases of CNS infections due to Mycobacterium abscessus complex have been reported. METHODS: We searched the Mycobacteriology Database of the National Taiwan University Hospital and identified patients with CNS infections due to NTM. RESULTS: A total of 15 patients, namely 4 HIV-seropositive patients and 11 HIV-seronegative patients, with CNS infections caused by NTM were identified during 2000-10. All of the HIV-seropositive patients had disseminated Mycobacterium avium complex infections. Among the 11 HIV-seronegative patients, NTM CNS infections were due to M. abscessus complex in 8 patients, M. avium complex in 2 patients and Mycobacterium kansasii in 1 patient. All the six preserved M. abscessus complex isolates were confirmed to be Mycobacterium massiliense by erm(41) PCR and 23S rRNA gene sequence analysis. Among the eight patients with infections due to M. abscessus complex, three had otolaryngological diseases, four had received neurosurgery and one had disseminated disease. Five patients received surgical debridement or intracranial device removal and three patients died of M. abscessus complex CNS infection. Among the five patients who survived, all received clarithromycin-based combination therapy with a median duration of 12 months and four received surgical intervention. All six isolates available for drug susceptibility testing showed uniform susceptibility to clarithromycin and five were susceptible to amikacin. CONCLUSIONS: Our study revealed that M. abscessus complex isolates, particularly M. massiliense, should be considered potential pathogens causing CNS infections. Long-duration clarithromycin-based combination therapy plus surgical intervention may provide the best chance of cure. PMID- 21980069 TI - Sequence types and plasmid carriage of uropathogenic Escherichia coli devoid of phenotypically detectable resistance. AB - OBJECTIVES: Plasmids play a major role in the dissemination of antibiotic resistance, and several studies have shown the association between specific resistance mechanisms and certain plasmid types and/or Escherichia coli lineages. This study describes the distribution of plasmids, replicon types, sequence types (STs) and ST complexes (STCs) of E. coli devoid of phenotypic resistance to 24 antibiotics. METHODS: Eighty E. coli isolates from urinary tract infections from four European countries were selected because of their lack of phenotypically detectable antibiotic resistance. The isolates were characterized to the phylogenetic group level using PCR and to ST by multilocus sequence typing. Plasmid carriage was assessed using S1 nuclease PFGE profiling and PCR-based replicon typing. RESULTS: Plasmids were detected in only 38/80 (47%) of the isolates; one (n = 18), two (n = 14), three (n = 5) and four (n = 1) plasmids. Six different replicon types were identified, the most common being a combination of IncFII and IncFIB. Most isolates belonged to phylogenetic group B2 and STC73 (n = 20), STC95 (n = 7) and ST420 (n = 6). A high proportion of STC73 isolates (75%) was devoid of plasmids. No association could be found between specific STs and replicon type. CONCLUSIONS: A large proportion of E. coli strains phenotypically devoid of antibiotic resistance were plasmid naive. Those isolates that harboured plasmids displayed replicon types similar to those of resistant isolates, but the distributions of STs and STCs were different. This may indicate chromosomally encoded mechanisms important for the stabilization of plasmids harbouring antibiotic resistance. PMID- 21980070 TI - Concentration-dependent effects of antimicrobials on Staphylococcus aureus toxin mediated cytokine production from peripheral blood mononuclear cells. AB - BACKGROUND: Toxins contribute to the pathogenicity of Staphylococcus aureus infections by inducing a dysregulated inflammatory response. This study evaluated the impact of anti-staphylococcal antibiotic exposures over an increasing concentration range on cytokine production from peripheral blood mononuclear cells (PBMCs) after S. aureus toxin exposures. METHODS: Human PBMCs were suspended in complete Roswell Park Memorial Institute (RPMI) 1640 medium with 10% fetal bovine serum at 10(6) cells/mL with 100 ng/mL S. aureus toxic shock syndrome toxin-1 (TSST-1), staphylococcal enterotoxin A (SEA), alpha-toxin or Panton-Valentine leucocidin (PVL). Vancomycin, trimethoprim/sulfamethoxazole, tigecycline, daptomycin, linezolid, clindamycin and azithromycin were added at a concentration range of 0.5-100 mg/L. Cytokine [interleukin-1beta (IL-1beta), IL 6, IL-8, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF alpha)] concentrations were measured in duplicate by ELISA following exposure and were compared with response with toxin alone. RESULTS: At concentrations approximating serum C(max), tigecycline decreased IL-6 by 52%-57% and IFN-gamma production by 43%-53% compared with toxin alone (P <= 0.05) and linezolid inhibited TNF-alpha by 12%-35% and IL-8 by 25%-42% (P <= 0.02). However, trimethoprim/sulfamethoxazole increased TNF-alpha and IL-8 production (P = 0.002). Clindamycin, daptomycin, vancomycin and azithromycin had no consistent significant effect at approximate serum C(max) concentrations. All antibiotics had a concentration-dependent effect on cytokine production, with tigecycline, clindamycin and trimethoprim/sulfamethoxazole being the most potent inhibitors of cytokine production at concentrations exceeding 25 mg/L. CONCLUSIONS: S. aureus toxins stimulate production of inflammatory cytokines in PBMCs. Antimicrobials with high tissue penetration, including tigecycline, clindamycin, trimethoprim/sulfamethoxazole and linezolid, reduced cytokine production, which, along with their antimicrobial effects, may have importance in the therapeutic outcome of severe infections. PMID- 21980071 TI - Disruption of the blaOXA-51-like gene by ISAba16 and activation of the blaOXA-58 gene leading to carbapenem resistance in Acinetobacter baumannii Ab244. AB - OBJECTIVES: This study examines the mechanism of carbapenem resistance in Acinetobacter baumannii isolate Ab244. METHODS: A multiplex PCR for the detection of the bla(OXA-23-like), bla(OXA-40-like), bla(OXA-51-like) and bla(OXA-58-like) families was performed. MICs of imipenem and meropenem were determined by the agar dilution method. The sequence surrounding the bla(OXA-132) gene was determined by amplification with primer pairs encompassing a part of fxsA and an acetyltransferase gene (GNAT). The sequence upstream of the bla(OXA-58) gene was determined by sequencing. SDS-PAGE and carO PCR were performed to check the integrity of the outer membrane proteins. RT-PCRs for the expression of the bla(OXA-132) gene and the bla(OXA-58) gene were performed. RESULTS: Isolate Ab244 harboured bla(OXA-132) belonging to the bla(OXA-51-like) gene cluster and a bla(OXA-58) gene. The 4239 bp region between fxsA and GNAT showed an insert of ISAba16 (where IS stands for insertion sequence) after the first 15 nucleotides of the bla(OXA-132) gene, with an 8 bp target site duplication at the 5' and 3' ends of ISAba16. The sequence oriented in the 5'->3' direction caused insertional inactivation of the bla(OXA-132) gene. The bla(OXA-58) gene was highly expressed by the promoters provided by an ISAba3-like structure found upstream of the gene. The isolate was resistant to meropenem and had intermediate resistance to imipenem, and was also positive for ISAba1. CONCLUSIONS: This is the first report showing ISAba16-mediated inactivation of the bla(OXA-132) gene in strain Ab244. The resistance to carbapenems in strain Ab244 is related to the acquisition of the bla(OXA-58) gene, here governed by an ISAba3-like element. PMID- 21980072 TI - Skp2 is required for incretin hormone-mediated beta-cell proliferation. AB - The glucoincretin hormone glucagon-like peptide-1 (GLP-1) and its analog exendin 4 (Ex-4) promote beta-cell growth and expansion. Here we report an essential role for Skp2, a substrate recognition component of SCF (Skp, Cullin, F-box) ubiquitin ligase, in promoting glucoincretin-induced beta-cell proliferation by regulating the cellular abundance of p27. In vitro, GLP-1 treatment increases Skp2 levels, which accelerates p27 degradation, whereas in vivo, loss of Skp2 prevents glucoincretin-induced beta-cell proliferation. Using inhibitors of phosphatidylinositol 3-kinase and Irs2 silencing RNA, we also show that the effects of GLP-1 in facilitating Skp2-dependent p27 degradation are mediated via the Irs2-phosphatidylinositol-3 kinase pathway. Finally, we show that down regulation of p27 occurs in islets from aged mice and humans, although in these islets, age-dependent accumulation of p16(Ink4a) prevent glucoincretin-induced beta-cell proliferation; however, ductal cell proliferation is maintained. Taken together, these data highlight a critical role for Skp2 in glucoincretin-induced beta-cell proliferation. PMID- 21980073 TI - CEBPD suppresses prolactin expression and prolactinoma cell proliferation. AB - Hyperprolactinemia, usually caused by a pituitary lactotroph tumor, leads to galactorrhea and infertility. Increased prolactin (PRL) levels may be due to enhanced PRL expression or proliferation of PRL-secreting cells. We hypothesize that PRL expression and PRL-secreting cell proliferation are linked. Using microarray-based gene expression profiling, we identified CCAAT-enhancer-binding protein delta (CEBPD) transcription factor as a critical gene that regulates both PRL expression and lactotroph cell proliferation. CEBPD expression levels are decreased approximately 7-fold in experimental rat prolactinoma cells. Forced expression of this transcription factor in PRL-secreting cells (GH3 and MMQ) inhibited PRL expression and cellular proliferation, and CEBPD knockdown by small interfering RNA leads to increased PRL expression in both cell lines. To determine mechanisms underlying this observation, we determined binding of CEBPD to the PRL promoter and also showed marked suppression (96%) of PRL promoter activity. CEBPD and Pit1 interact and attenuate each other's binding to the PRL promoter. CEBPD also suppresses expression of proliferation-related genes, including c-Myc, survivin, as well as cyclins B1, B2, and D1. These results show that PRL expression and cell proliferation are controlled in part by CEBPD. PMID- 21980074 TI - Novel role for SGK3 in glucose homeostasis revealed in SGK3/Akt2 double-null mice. AB - The phosphatidylinositol-3-kinase-dependent kinase, Akt2, plays a central role in mediating insulin effects in glucose-metabolizing tissues. Akt2 knockout mice display insulin resistance with a reactive increase in pancreatic islet mass and hyperinsulinemia. The related phosphatidylinositol-3-kinase-dependent kinase, serum- and glucocorticoid-regulated kinase 3 (SGK3), is essential for normal postnatal hair follicle development but plays no apparent role in glucose homeostasis. We report here an unexpected role of SGK3 in islet beta-cell function, which is revealed in Akt2/SGK3 double-knockout (DKO) mice. DKO mice have markedly worse glucose homeostasis than Akt2 single-null animals, including greater baseline glucose, and greater rise in blood glucose after glucose challenge. However, surprisingly, our data strongly support the idea that this exacerbation of the glucose-handling defect is due to impaired beta-cell function, rather than increased insulin resistance in peripheral tissues. DKO mice had lower plasma insulin and C-peptide levels, lower beta-cell mass, reduced glucose-stimulated insulin secretion, and greater sensitivity to exogenous insulin than Akt2 single nulls. We further demonstrated that SGK3 is strongly expressed in normal mouse islets and, interestingly, that beta-catenin expression is dramatically lower in the islets of DKO mice than in those of Akt2(-/ )/SGK3(+/+) or Akt2(-/-)/SGK3(+/-) mice. Taken together, these data strongly suggest that SGK3 plays a previously unappreciated role in glucose homeostasis, likely through direct effects within beta-cells, to stimulate proliferation and insulin release, at least in part by controlling the expression and activity of beta-catenin. PMID- 21980077 TI - Appendicitis. PMID- 21980075 TI - TSH compensates thyroid-specific IGF-I receptor knockout and causes papillary thyroid hyperplasia. AB - Although TSH stimulates all aspects of thyroid physiology IGF-I signaling through a tyrosine kinase-containing transmembrane receptor exhibits a permissive impact on TSH action. To better understand the importance of the IGF-I receptor in the thyroid in vivo, we inactivated the Igf1r with a Tg promoter-driven Cre-lox system in mice. We studied male and female mice with thyroidal wild-type, Igf1r(+/-), and Igf1r(-/-) genotypes. Targeted Igf1r inactivation did transiently reduce thyroid hormone levels and significantly increased TSH levels in both heterozygous and homozygous mice without affecting thyroid weight. Histological analysis of thyroid tissue with Igf1r inactivation revealed hyperplasia and heterogeneous follicle structure. From 4 months of age, we detected papillary thyroid architecture in heterozygous and homozygous mice. We also noted increased body weight of male mice with a homozygous thyroidal null mutation in the Igf1r locus, compared with wild-type mice, respectively. A decrease of mRNA and protein for thyroid peroxidase and increased mRNA and protein for IGF-II receptor but no significant mRNA changes for the insulin receptor, the TSH receptor, and the sodium-iodide-symporter in both Igf1r(+/-) and Igf1r(-/-) mice were detected. Our results suggest that the strong increase of TSH benefits papillary thyroid hyperplasia and completely compensates the loss of IGF-I receptor signaling at the level of thyroid hormones without significant increase in thyroid weight. This could indicate that the IGF-I receptor signaling is less essential for thyroid hormone synthesis but maintains homeostasis and normal thyroid morphogenesis. PMID- 21980076 TI - Low-energy multistage atrial defibrillation therapy terminates atrial fibrillation with less energy than a single shock. AB - BACKGROUND: Implantable device therapy of atrial fibrillation (AF) is limited by pain from high-energy shocks. We developed a low-energy multistage defibrillation therapy and tested it in a canine model of AF. METHODS AND RESULTS: AF was induced by burst pacing during vagus nerve stimulation. Our novel defibrillation therapy consisted of 3 stages: stage (ST) 1 (1-4 low-energy biphasic [BP] shocks), ST2 (6-10 ultralow-energy monophasic [MP] shocks), and ST3 (antitachycardia pacing). First, ST1 testing compared single or multiple MP and BP shocks. Second, several multistage therapies were tested: ST1 versus ST1+ST3 versus ST1+ST2+ST3. Third, 3 shock vectors were compared: superior vena cava to distal coronary sinus, proximal coronary sinus to left atrial appendage, and right atrial appendage to left atrial appendage. The atrial defibrillation threshold (DFT) of 1 BP shock was <1 MP shock (0.55 +/- 0.1 versus 1.38 +/- 0.31 J, P=0.003). Two to 3 BP shocks terminated AF with lower peak voltage than 1 BP or 1 MP shock and with lower atrial DFT than 4 BP shocks. Compared with ST1 therapy alone, ST1+ST3 lowered the atrial DFT moderately (0.51 +/- 0.46 versus 0.95 +/- 0.32 J, P=0.036), whereas 3-stage therapy (ST1+ST2+ST3) dramatically lowered the atrial DFT (0.19 +/- 0.12 versus 0.95 +/- 0.32 J for ST1 alone, P=0.0012). Finally, the 3-stage therapy was equally effective for all studied vectors. CONCLUSIONS: Three-stage electrotherapy significantly reduces the AF DFT and opens the door to low-energy atrial defibrillation at or below the pain threshold. PMID- 21980078 TI - Septal deformation patterns delineate mechanical dyssynchrony and regional differences in contractility: analysis of patient data using a computer model. AB - BACKGROUND: Response to cardiac resynchronization therapy depends both on dyssynchrony and (regional) contractility. We hypothesized that septal deformation can be used to infer integrated information on dyssynchrony and regional contractility, and thereby predict cardiac resynchronization therapy response. METHODS AND RESULTS: In 132 cardiac resynchronization therapy candidates with left bundle branch block (LBBB)-like electrocardiogram morphology (left ventricular ejection fraction 19+/-6%; QRS width 170+/-23 ms), longitudinal septal strain was assessed by speckle tracking echocardiography. To investigate the effects of dyssynchronous activation and differences in septal and left ventricular free wall contractility on septal deformation pattern, we used the CircAdapt computer model of the human heart and circulation. In the patients, 3 characteristic septal deformation patterns were identified: LBBB-1=double-peaked systolic shortening (n=28); LBBB-2=early systolic shortening followed by prominent systolic stretching (n=34); and LBBB-3=pseudonormal shortening with less pronounced late systolic stretch (n=70). LBBB-3 revealed more scar (2 [2-5] segments) compared with LBBB-1 and LBBB-2 (both 0 [0-1], P<0.05). In the model, imposing a time difference of activation between septum and left ventricular free wall resulted in pattern LBBB-1. This transformed into pattern LBBB-2 by additionally simulating septal hypocontractility, and into pattern LBBB-3 by imposing additional left ventricular free wall or global left ventricular hypocontractility. Improvement of left ventricular ejection fraction and reduction of left ventricular volumes after cardiac resynchronization therapy were most pronounced in LBBB-1 and worst in LBBB-3 patients. CONCLUSIONS: A double-peaked systolic septal deformation pattern is characteristic for LBBB and results from intraventricular dyssynchrony. Abnormal contractility modifies this pattern. A computer model can be helpful in understanding septal deformation and predicting cardiac resynchronization therapy response. PMID- 21980079 TI - Genomics is not enough. PMID- 21980084 TI - Stem cells. Human cells cloned--almost. PMID- 21980085 TI - Stem cells. Where do human eggs come from? PMID- 21980086 TI - Newsmaker interview: Joe Selby. Sifting medical records to determine which therapies work best. Interview by Eliot Marshall. PMID- 21980087 TI - Clinical research. Gene therapists celebrate a decade of progress. PMID- 21980088 TI - Nobel Prize in physics. Curious cosmic speed-up nabs Nobel Prize. PMID- 21980089 TI - Nobel Prize in physiology or medicine. Immunology prize overshadowed by untimely death of awardee. PMID- 21980090 TI - Geology. An epoch debate. PMID- 21980091 TI - A global perspective on the Anthropocene. PMID- 21980092 TI - Geology. A sign of our times. PMID- 21980093 TI - Strategic success for hydropower in Laos. PMID- 21980094 TI - Justifiable changes to Indicators survey. PMID- 21980095 TI - Exxon-Mobil funding overstated. PMID- 21980097 TI - Conservation. Paleolithic art in peril: policy and science collide at Altamira Cave. PMID- 21980098 TI - Microbiology. The guts of dietary habits. PMID- 21980099 TI - Ecology. Resilience to blooms. PMID- 21980100 TI - Immunology. Neuroimmune communication. PMID- 21980101 TI - Evolution. The genomic basis of local climatic adaptation. PMID- 21980102 TI - Physics. Toward control of large-scale quantum computing. PMID- 21980103 TI - Geochemistry. Diamond window into the lower mantle. PMID- 21980104 TI - Three-dimensional Anderson localization of ultracold matter. AB - Anderson localization (AL) is a ubiquitous interference phenomenon in which waves fail to propagate in a disordered medium. We observe three-dimensional AL of noninteracting ultracold matter by allowing a spin-polarized atomic Fermi gas to expand into a disordered potential. A two-component density distribution emerges consisting of an expanding mobile component and a nondiffusing localized component. We extract a mobility edge that increases with the disorder strength, whereas the thermally averaged localization length is shown to decrease with disorder strength and increase with particle energy. These measurements provide a benchmark for more sophisticated theories of AL. PMID- 21980106 TI - Dispersible exfoliated zeolite nanosheets and their application as a selective membrane. AB - Thin zeolite films are attractive for a wide range of applications, including molecular sieve membranes, catalytic membrane reactors, permeation barriers, and low-dielectric-constant materials. Synthesis of thin zeolite films using high aspect-ratio zeolite nanosheets is desirable because of the packing and processing advantages of the nanosheets over isotropic zeolite nanoparticles. Attempts to obtain a dispersed suspension of zeolite nanosheets via exfoliation of their lamellar precursors have been hampered because of their structure deterioration and morphological damage (fragmentation, curling, and aggregation). We demonstrated the synthesis and structure determination of highly crystalline nanosheets of zeolite frameworks MWW and MFI. The purity and morphological integrity of these nanosheets allow them to pack well on porous supports, facilitating the fabrication of molecular sieve membranes. PMID- 21980105 TI - Detection of pulsed gamma rays above 100 GeV from the Crab pulsar. AB - We report the detection of pulsed gamma rays from the Crab pulsar at energies above 100 giga-electron volts (GeV) with the Very Energetic Radiation Imaging Telescope Array System (VERITAS) array of atmospheric Cherenkov telescopes. The detection cannot be explained on the basis of current pulsar models. The photon spectrum of pulsed emission between 100 mega-electron volts and 400 GeV is described by a broken power law that is statistically preferred over a power law with an exponential cutoff. It is unlikely that the observation can be explained by invoking curvature radiation as the origin of the observed gamma rays above 100 GeV. Our findings require that these gamma rays be produced more than 10 stellar radii from the neutron star. PMID- 21980107 TI - A self-quenched defect glass in a colloid-nematic liquid crystal composite. AB - Colloidal particles immersed in liquid crystals frustrate orientational order. This generates defect lines known as disclinations. At the core of these defects, the orientational order drops sharply. We have discovered a class of soft solids, with shear moduli up to 10(4) pascals, containing high concentrations of colloidal particles (volume fraction phi ? 20%) directly dispersed into a nematic liquid crystal. Confocal microscopy and computer simulations show that the mechanical strength derives from a percolated network of defect lines entangled with the particles in three dimensions. Such a "self-quenched glass" of defect lines and particles can be considered a self-organized analog of the "vortex glass" state in type II superconductors. PMID- 21980108 TI - Adaptation to climate across the Arabidopsis thaliana genome. AB - Understanding the genetic bases and modes of adaptation to current climatic conditions is essential to accurately predict responses to future environmental change. We conducted a genome-wide scan to identify climate-adaptive genetic loci and pathways in the plant Arabidopsis thaliana. Amino acid-changing variants were significantly enriched among the loci strongly correlated with climate, suggesting that our scan effectively detects adaptive alleles. Moreover, from our results, we successfully predicted relative fitness among a set of geographically diverse A. thaliana accessions when grown together in a common environment. Our results provide a set of candidates for dissecting the molecular bases of climate adaptations, as well as insights about the prevalence of selective sweeps, which has implications for predicting the rate of adaptation. PMID- 21980110 TI - Assurances are sought that policy of personal health budgets will follow evidence. PMID- 21980109 TI - A map of local adaptation in Arabidopsis thaliana. AB - Local adaptation is critical for species persistence in the face of rapid environmental change, but its genetic basis is not well understood. Growing the model plant Arabidopsis thaliana in field experiments in four sites across the species' native range, we identified candidate loci for local adaptation from a genome-wide association study of lifetime fitness in geographically diverse accessions. Fitness-associated loci exhibited both geographic and climatic signatures of local adaptation. Relative to genomic controls, high-fitness alleles were generally distributed closer to the site where they increased fitness, occupying specific and distinct climate spaces. Independent loci with different molecular functions contributed most strongly to fitness variation in each site. Independent local adaptation by distinct genetic mechanisms may facilitate a flexible evolutionary response to changing environment across a species range. PMID- 21980111 TI - GP surgery recommends private treatment to patients after cutbacks. PMID- 21980112 TI - Effects of pH on potassium: new explanations for old observations. AB - Maintenance of extracellular K(+) concentration within a narrow range is vital for numerous cell functions, particularly electrical excitability of heart and muscle. Potassium homeostasis during intermittent ingestion of K(+) involves rapid redistribution of K(+) into the intracellular space to minimize increases in extracellular K(+) concentration, and ultimate elimination of the K(+) load by renal excretion. Recent years have seen great progress in identifying the transporters and channels involved in renal and extrarenal K(+) homeostasis. Here we apply these advances in molecular physiology to understand how acid-base disturbances affect serum potassium. PMID- 21980113 TI - Balancing calcium signals through TRPC5 and TRPC6 in podocytes. AB - Calcium (Ca(2+)) ions are important mediators of cellular homeostasis owing to their ability to elicit a dynamic, transient, and tightly regulated range of biochemical responses. More than a decade ago, a nonselective, Ca(2+)-permeable, cationic conductance was identified in podocytes downstream of angiotensin II (Ang II) signaling, but its molecular structure remained elusive. Six years ago, transient receptor potential canonical 6 (TRPC6) mutations were found in families with hereditary FSGS, and TRPC5 and TRPC6 channels are now known as the Ca(2+) influx pathways for this previously described, nonselective, cationic current in podocytes. Ang II activation engages this Ca(2+) influx to modulate the actin cytoskeleton in podocytes. These discoveries dovetail with previously described regulation of actin dynamics by the Ca(2+)-activated phosphatase, calcineurin, and the emergence of Rho GTPases as critical regulators of podocyte function in health and disease. Understanding the interconnected signaling regulated by Ca(2+) currents offers potential new therapeutic targets and highlights the notion that synergistic therapies targeting multiple levels of biochemistry may be useful in treating proteinuric kidney disease. PMID- 21980114 TI - Regional differences in dialysis care and mortality among American Indians and Alaska Natives. AB - American Indians/Alaska Natives (AIANs) compose a heterogeneous population that includes geographically distinct tribal communities, many with high rates of ESRD. Regional features of dialysis care and mortality are unknown in this population. Here, we describe the structure of dialysis care and mortality of adult AIANs who initiated maintenance dialysis during 1995-2008 in different regions of the US. Overall, 13,716 AIANs received dialysis at 2054 facilities. Approximately 10% (n = 197) of these facilities provided care to two-thirds (n = 9011) of AIANs. AIANs from the Southwest and Alaska were concentrated in relatively few dialysis facilities whereas those in the Eastern US and Pacific Coast were distributed more diffusely. Despite comparably high rates of poverty, diabetes, and cardiovascular disease, annual mortality rates were lower in the Southwest (13.9%) compared with the Southern Plains (23.2%), Alaska (21.2%), Eastern US (20.0%), Northern Plains (20.8%), and Pacific Coast (22.0%). These regional differences were consistent over time and persisted after adjusting for sociodemographic and clinical variables and area-based poverty. In conclusion, regional differences in the structure of dialysis care and patient mortality exist among AIANs. Southwestern AIANs experience the highest concentration of dialysis care and the lowest mortality. Our findings suggest that an area-based approach examining the care structure of relatively few dialysis facilities may delineate determinants of these differences and improve the quality of care to many AIAN communities. PMID- 21980115 TI - The biochemical properties of the Francisella pathogenicity island (FPI)-encoded proteins IglA, IglB, IglC, PdpB and DotU suggest roles in type VI secretion. AB - The Francisella pathogenicity island (FPI) encodes proteins thought to compose a type VI secretion system (T6SS) that is required for the intracellular growth of Francisella novicida. In this work we used deletion mutagenesis and genetic complementation to determine that the intracellular growth of F. novicida was dependent on 14 of the 18 genes in the FPI. The products of the iglABCD operon were localized by the biochemical fractionation of F. novicida, and Francisella tularensis LVS. Sucrose gradient separation of water-insoluble material showed that the FPI-encoded proteins IglA, IglB and IglC were found in multiple fractions, especially in a fraction that did not correspond to a known membrane fraction. We interpreted these data to suggest that IglA, IglB and IglC are part of a macromolecular structure. Analysis of published structural data suggested that IglC is an analogue of Hcp, which is thought to form long nano-tubes. Thus the fractionation properties of IglA, IglB and IglC are consistent with the current model of the T6SS apparatus, which supposes that IglA and IglB homologues form an outer tube structure that surrounds an inner tube composed of Hcp (IglC) subunits. Fractionation of F. novicida expressing FLAG-tagged DotU (IcmH homologue) and PdpB (IcmF homologue) showed that these proteins localize to the inner membrane. Deletion of dotU led to the cleavage of PdpB, suggesting an interaction of these two proteins that is consistent with results obtained with other T6SSs. Our results may provide a mechanistic basis for many of the studies that have examined the virulence properties of Francisella mutants in FPI genes, namely that the observed phenotypes of the mutants are the result of the disruption of the FPI-encoded T6SS structure. PMID- 21980116 TI - On sialic acid transport and utilization by Vibrio cholerae. PMID- 21980117 TI - Biocontrol of Fusarium head blight: interactions between Trichoderma and mycotoxigenic Fusarium. AB - Fusarium head blight (FHB) is a re-emerging wheat disease that causes extensive damage through direct losses in yield and quality due to the presence of damaged Fusarium kernels and their associated mycotoxins such as the trichothecene deoxynivalenol (DON). Biological control, including the treatment of crop residues with antagonists, in order to reduce pathogen inoculum of FHB, holds considerable promise. Ten Trichoderma isolates, previously selected for their ability to grow in the presence of DON, were preliminarily investigated as potential antagonists against Fusarium culmorum and F. graminearum mycotoxigenic strains in plate confrontation assays. The three Trichoderma isolates showing antibiosis and mycoparasitism were evaluated for their capacity to inhibit DON production by F. graminearum and F. culmorum on two natural substrates. The expression of some chitinase-encoding genes by the two best resulting Trichoderma strains, during interaction with F. culmorum and F. graminearum, was monitored. All investigated genes from chitinase subgroups A, B and the new subgroup C responded to mycoparasitic conditions and were upregulated before contact and/or when in contact with the host. T. gamsii 6085, the best antagonist, was finally used in a competition test against F. culmorum and F. graminearum on natural substrates, using a qPCR approach to evaluate its effect on the pathogen's growth and DON production in haulms and rice. This test confirmed the ability of T. gamsii 6085 to antagonize the pathogens on rice. On wheat haulms, an extreme oligotrophic environment, T. gamsii 6085 seemed to develop very poorly and the growth of both the pathogens was unaffected by the presence of the antagonist. PMID- 21980118 TI - Target recognition, resistance, immunity and genome mining of class II bacteriocins from Gram-positive bacteria. AB - Due to their very potent antimicrobial activity against diverse food-spoiling bacteria and pathogens and their favourable biochemical properties, peptide bacteriocins from Gram-positive bacteria have long been considered promising for applications in food preservation or medical treatment. To take advantage of bacteriocins in different applications, it is crucial to have detailed knowledge on the molecular mechanisms by which these peptides recognize and kill target cells, how producer cells protect themselves from their own bacteriocin (self immunity) and how target cells may develop resistance. In this review we discuss some important recent progress in these areas for the non-lantibiotic (class II) bacteriocins. We also discuss some examples of how the current wealth of genome sequences provides an invaluable source in the search for novel class II bacteriocins. PMID- 21980119 TI - Statins and HIV medication: a view from primary care. PMID- 21980120 TI - Commission calls for medical training to become more generalist. PMID- 21980121 TI - Quantitative sensory testing of persistent pain after video-assisted thoracic surgery lobectomy. AB - BACKGROUND: Video-assisted thoracic surgery (VATS) lobectomy may potentially reduce the risk of post-thoracotomy pain syndrome (PTPS). However, it may still carry a risk of intraoperative nerve damage and thereby development of PTPS. Thus, our aim was to present a detailed long-term neurophysiological characterization of PTPS after VATS. METHODS: Quantitative sensory testing, using thermal and mechanical stimuli, was performed in 13 PTPS patients and 35 pain free patients recruited 33 months after VATS lobectomy. RESULTS: When comparing the operated side with the control side in PTPS patients, increased thresholds of tactile and warmth detection were observed, while in pain-free patients, increased thresholds of warmth detection, cool detection, and heat pain were demonstrated. At the anterior porthole, pain-free patients displayed increased threshold to thermal detection when compared with the control side. Only side-to side difference for tactile detection threshold was increased in PTPS patients compared with pain-free patients. Assessment of central sensitization showed no significant differences within or between PTPS and pain-free patients nor did group comparison of area of hypo- and hyperaesthesia to cool. Anxiety and depression scores (HADS) were higher in PTPS patients, but the area of hyper- and hypoaesthesia did not differ significantly between HADS groups. CONCLUSIONS: Increased sensory thresholds suggest nerve injury to be present on the operated side in both PTPS and pain-free patients. However, no significant quantitative differences between PTPS and pain-free patients could be found, implicating the presence of factors other than intercostal nerve injury as important for development of PTPS after VATS lobectomy. PMID- 21980122 TI - Validity of the 6 min walk test in prediction of the anaerobic threshold before major non-cardiac surgery. AB - BACKGROUND: For perioperative risk stratification, a robust, practical test could be used where cardiopulmonary exercise testing (CPET) is unavailable. The aim of this study was to assess the utility of the 6 min walk test (6MWT) distance to discriminate between low and high anaerobic threshold (AT) in patients awaiting major non-cardiac surgery. METHODS: In 110 participants, we obtained oxygen consumption at the AT from CPET and recorded the distance walked (in m) during a 6MWT. Receiver operating characteristic (ROC) curve analysis was used to derive two different cut-points for 6MWT distance in predicting an AT of <11 ml O(2) kg( 1) min(-1); one using the highest sum of sensitivity and specificity (conventional method) and the other adopting a 2:1 weighting in favour of sensitivity. In addition, using a novel linear regression-based technique, we obtained lower and upper cut-points for 6MWT distance that are predictive of an AT that is likely to be (P>=0.75) <11 or >11 ml O(2) kg(-1) min(-1). RESULTS: The ROC curve analysis revealed an area under the curve of 0.85 (95% confidence interval, 0.77-0.91). The optimum cut-points were <440 m (conventional method) and <502 m (sensitivity-weighted approach). The regression-based lower and upper 6MWT distance cut-points were <427 and >563 m, respectively. CONCLUSIONS: Patients walking >563 m in the 6MWT do not routinely require CPET; those walking <427 m should be referred for further evaluation. In situations of 'clinical uncertainty' (>=427 but <=563 m), the number of clinical risk factors and magnitude of surgery should be incorporated into the decision-making process. The 6MWT is a useful clinical tool to screen and risk stratify patients in departments where CPET is unavailable. PMID- 21980123 TI - Role of KATP channels in the maintenance of ventricular fibrillation in cardiomyopathic human hearts. AB - RATIONALE: Ventricular fibrillation (VF) leads to global ischemia. The modulation of ischemia-dependent pathways may alter the electrophysiological evolution of VF. OBJECTIVE: We addressed the hypotheses that there is regional disease-related expression of K(ATP) channels in human cardiomyopathic hearts and that K(ATP) channel blockade promotes spontaneous VF termination by attenuating spatiotemporal dispersion of refractoriness. METHODS AND RESULTS: In a human Langendorff model, electric mapping of 6 control and 9 treatment (10 MUmol/L glibenclamide) isolated cardiomyopathic hearts was performed. Spontaneous defibrillation was studied and mean VF cycle length was compared regionally at VF onset and after 180 seconds between control and treatment groups. K(ATP) subunit gene expression was compared between LV endocardium versus epicardium in myopathic hearts. Spontaneous VF termination occurred in 1 of 6 control hearts and 7 of 8 glibenclamide-treated hearts (P=0.026). After 180 seconds of ischemia, a transmural dispersion in VF cycle length was observed between epicardium and endocardium (P=0.001), which was attenuated by glibenclamide. There was greater gene expression of all K(ATP) subunit on the endocardium compared with the epicardium (P<0.02). In an ischemic rat heart model, transmural dispersion of refractoriness (DeltaERP(Transmural)=ERP(Epicardium)-ERP(Endocardium)) was verified with pacing protocols. DeltaERP(Transmural) in control was 5 +/- 2 ms and increased to 36 +/- 5 ms with ischemia. This effect was greatly attenuated by glibenclamide (DeltaERP(Transmural) for glibenclamide+ischemia=4.9 +/- 4 ms, P=0.019 versus control ischemia). CONCLUSIONS: K(ATP) channel subunit gene expression is heterogeneously altered in the cardiomyopathic human heart. Blockade of K(ATP) channels promotes spontaneous defibrillation in cardiomyopathic human hearts by attenuating the ischemia-dependent spatiotemporal heterogeneity of refractoriness during early VF. PMID- 21980124 TI - Mitochondrial STAT3 activation and cardioprotection by ischemic postconditioning in pigs with regional myocardial ischemia/reperfusion. AB - RATIONALE: Timely restoration of coronary blood flow is the only way to salvage myocardium from infarction, but reperfusion per se brings on additional injury. Such reperfusion injury and the resulting size of myocardial infarction is attenuated by ischemic postconditioning, ie, the repeated brief interruption of coronary blood flow during early reperfusion. The signal transduction of ischemic postconditioning is under intense investigation, but no signaling step has yet been identified as causal for such protection in larger mammals in situ. OBJECTIVE: We have now in an in situ pig model of regional myocardial ischemia/reperfusion addressed the role of mitochondrial signal transducer and activator of transcription 3 (STAT3). METHODS AND RESULTS: We demonstrated reduction of infarct size by ischemic postconditioning (26 +/- 3% of area at risk versus 38 +/- 2% in controls with immediate full reperfusion) along with more markedly increased tyrosine(705) phosphorylation of STAT3 in myocardial biopsies (at 10 minutes reperfusion: 9.2 +/- 3.0-fold from baseline versus 6.6 +/- 2.9 fold in controls with immediate full reperfusion). Increased tyrosine(705) phosphorylation of STAT3 and better preservation of complex 1 respiration and calcium retention capacity were also present in isolated mitochondria from postconditioned myocardium in vitro. Prior janus kinase/STAT inhibition with AG490 in vivo abrogated the infarct size reduction and the better preservation of mitochondrial function, and the STAT3 inhibitor Stattic in vitro also abrogated better preservation of mitochondrial function. CONCLUSIONS: Our data support a causal role for mitochondrial STAT3 activation to mediate cardioprotection through better mitochondrial function. PMID- 21980125 TI - AMPKalpha2 deletion exacerbates neointima formation by upregulating Skp2 in vascular smooth muscle cells. AB - RATIONALE: Adenosine monophosphate-activated protein kinase (AMPK), a metabolic and redox sensor, is reported to suppress cell proliferation of nonmalignant and tumor cells. Whether AMPKalpha alters vascular neointima formation induced by vascular injury is unknown. OBJECTIVE: The aim of this study was to determine the roles of AMPKalpha in the development of vascular neointima hyperplasia and to elucidate the underlying mechanisms. METHODS AND RESULTS: Vascular smooth muscle cell (VSMC) proliferation and neointimal hyperplasia were evaluated in cultured VSMCs and wire-injured mouse carotid arteries from wild-type (WT, C57BL/6J), AMPKalpha2(-/-), and AMPKalpha1(-/-) mice. Mouse VSMCs derived from aortas of AMPKalpha2(-/-) mice exhibited increased proliferation compared with either WT or AMPKalpha1(-/-) VSMCs. Further, deletion of AMPKalpha2 but not AMPKalpha1 reduced the level of p27(Kip1), a cyclin-dependent kinase inhibitor, and increased the level of S-phase kinase-associated protein 2 (Skp2), a known E3 ubiquitin ligase for p27(Kip1), through activation of p52 nuclear factor kappa B (NF-kappaB)-2. Moreover, either pharmacological (ie, through compound C) or genetical (ie, through AMPKalpha2-specific siRNA) inhibition of AMPK decreased p27(Kip1) levels but increased the abundance of Skp2 in human VSMCs. Furthermore, gene silencing of Skp2 reversed the levels of p27(Kip1) and VSMCs proliferation. Finally, neointima formation after mechanical arterial injury was increased in AMPKalpha2( /-) but not AMPKalpha1(-/-) mice. CONCLUSIONS: These findings indicate that deletion of AMPKalpha2 through p52-Skp2-mediated ubiquitination and degradation of p27(Kip1) accentuates neointimal hyperplasia in response to wire injury. PMID- 21980126 TI - Epigenetic regulation of endothelial lineage committed genes in pro-angiogenic hematopoietic and endothelial progenitor cells. AB - RATIONALE: Proangiogenic hematopoietic and endothelial progenitor cells (EPCs) contribute to postnatal neovascularization, but the mechanisms regulating differentiation to the endothelial lineage are unclear. OBJECTIVE: To elucidate the epigenetic control of endothelial gene expression in proangiogenic cells and EPCs. METHODS AND RESULTS: Here we demonstrate that the endothelial nitric oxide synthase (eNOS) promoter is epigenetically silenced in proangiogenic cells (early EPCs), CD34(+) cells, and mesoangioblasts by DNA methylation and prominent repressive histone H3K27me3 marks. In order to reverse epigenetic silencing to facilitate endothelial commitment, we used 3-deazaneplanocin A, which inhibits the histone methyltransferase enhancer of zest homolog 2 and, thereby, reduces H3K27me3. 3-Deazaneplanocin A was not sufficient to increase eNOS expression, but the combination of 3-deazaneplanocin A and the histone deacetylase inhibitor Trichostatin A augmented eNOS expression, indicating that the concomitant inhibition of silencing histone modification and enhancement of activating histone modification facilitates eNOS expression. In ischemic tissue, hypoxia plays a role in recruiting progenitor cells. Therefore, we examined the effect of hypoxia on epigenetic modifications. Hypoxia modulated the balance of repressive to active histone marks and increased eNOS mRNA expression. The reduction of repressive H3K27me3 was associated with an increase of the histone demethylase Jmjd3. Silencing of Jmjd3 induced apoptosis and senescence in proangiogenic cells and inhibited hypoxia-mediated up-regulation of eNOS expression in mesoangioblasts. CONCLUSIONS: These findings provide evidence that histone modifications epigenetically control the eNOS promoter in proangiogenic cells. PMID- 21980129 TI - Integrin alpha6(high) cell population functions as an initiator in tumorigenesis and relapse of human liposarcoma. AB - The relapse and resistance to chemo- and radiotherapy are main problems in the treatment of human liposarcoma. It is important to find a functional marker existing in the liposarcoma cells for targeting. In this article, we established a new sub-cell line SW872-S cells with high tumorigenicity from human liposarcoma SW872 cells by repeated inoculation approach. The characteristic of the sub-cell line is linked to the high levels of integrin alpha6 on the surface. The integrin alpha6(high) cells show much higher tumor initiation and self-renewal potential in vivo than integrin alpha6(low) cells do. Targeting integrin alpha6 with its specific short interfering RNA and antibody significantly inhibits the cell adhesion to laminin and the tumor growth in vitro and in vivo, respectively. Interestingly, integrin alpha6 marks almost all of the surgical biopsy specimens of patients with liposarcoma relapse. Moreover, integrin alpha6 is found to coexpress with CD13, which might contribute to the antiapoptosis ability of integrin alpha6(high) cells. Consistently, integrin alpha6(high) cells are more sensitive to the CD13 inhibitor bestatin, and 61% of 23 other human tumor cell lines also contain integrin alpha6(high) CD13(high) subgroup. These results provide evidence, for the first time, to our knowledge, that integrin alpha6 and CD13 can serve as functional markers of the tumor-initiation subcell population in human liposarcoma as well as other cancers for therapeutic targeting. PMID- 21980127 TI - Hydrogen sulfide as endothelium-derived hyperpolarizing factor sulfhydrates potassium channels. AB - RATIONALE: Nitric oxide, the classic endothelium-derived relaxing factor (EDRF), acts through cyclic GMP and calcium without notably affecting membrane potential. A major component of EDRF activity derives from hyperpolarization and is termed endothelium-derived hyperpolarizing factor (EDHF). Hydrogen sulfide (H(2)S) is a prominent EDRF, since mice lacking its biosynthetic enzyme, cystathionine gamma lyase (CSE), display pronounced hypertension with deficient vasorelaxant responses to acetylcholine. OBJECTIVE: The purpose of this study was to determine if H(2)S is a major physiological EDHF. METHODS AND RESULTS: We now show that H(2)S is a major EDHF because in blood vessels of CSE-deleted mice, hyperpolarization is virtually abolished. H(2)S acts by covalently modifying (sulfhydrating) the ATP-sensitive potassium channel, as mutating the site of sulfhydration prevents H(2)S-elicited hyperpolarization. The endothelial intermediate conductance (IK(Ca)) and small conductance (SK(Ca)) potassium channels mediate in part the effects of H(2)S, as selective IK(Ca) and SK(Ca) channel inhibitors, charybdotoxin and apamin, inhibit glibenclamide-insensitive, H(2)S-induced vasorelaxation. CONCLUSIONS: H(2)S is a major EDHF that causes vascular endothelial and smooth muscle cell hyperpolarization and vasorelaxation by activating the ATP-sensitive, intermediate conductance and small conductance potassium channels through cysteine S-sulfhydration. Because EDHF activity is a principal determinant of vasorelaxation in numerous vascular beds, drugs influencing H(2)S biosynthesis offer therapeutic potential. PMID- 21980128 TI - Akt/mTOR counteract the antitumor activities of cixutumumab, an anti-insulin-like growth factor I receptor monoclonal antibody. AB - Recent reports have shown limited anticancer therapeutic efficacy of insulin-like growth factor receptor (IGF-1R)-targeted monoclonal antibodies (mAb), but the resistance mechanisms have not been completely identified. Because cooperation between epidermal growth factor receptor (EGFR) and IGF-IR could cause resistance to inhibitors of individual receptor tyrosine kinases, we investigated the involvement of EGFR signaling in resistance to IGF-1R mAb and the underlying mechanisms of action. Most head and neck squamous cell carcinoma (HNSCC) tissues had coexpression of total and phosphorylated IGF-1R and EGFR at high levels compared with paired adjacent normal tissues. Treatment with cixutumumab (IMC A12), a fully humanized IgG1 mAb, induced activation of Akt and mTOR, resulting in de novo synthesis of EGFR, Akt1, and survivin proteins and activation of the EGFR pathway in cixutumumab-resistant HNSCC and non-small cell lung cancer (NSCLC) cells. Targeting mTOR and EGFR pathways by treatment with rapamycin and cetuximab (an anti-EGFR mAb), respectively, prevented cixutumumab-induced expression of EGFR, Akt, and survivin and induced synergistic antitumor effects in vitro and in vivo. These data show that resistance to IGF-1R inhibition by mAbs is associated with Akt/mTOR-directed enhanced synthesis of EGFR, Akt1, and survivin. Our findings suggest that Akt/mTOR might be effective targets to overcome the resistance to IGF-1R mAbs in HNSCC and NSCLC. PMID- 21980130 TI - Characterization of the cellular and antitumor effects of MPI-0479605, a small molecule inhibitor of the mitotic kinase Mps1. AB - Mps1 is a dual specificity protein kinase that is essential for the bipolar attachment of chromosomes to the mitotic spindle and for maintaining the spindle assembly checkpoint until all chromosomes are properly attached. Mps1 is expressed at high levels during mitosis and is abundantly expressed in cancer cells. Disruption of Mps1 function induces aneuploidy and cell death. We report the identification of MPI-0479605, a potent and selective ATP competitive inhibitor of Mps1. Cells treated with MPI-0479605 undergo aberrant mitosis, resulting in aneuploidy and formation of micronuclei. In cells with wild-type p53, this promotes the induction of a postmitotic checkpoint characterized by the ATM- and RAD3-related-dependent activation of the p53-p21 pathway. In both wild type and p53 mutant cells lines, there is a growth arrest and inhibition of DNA synthesis. Subsequently, cells undergo mitotic catastrophe and/or an apoptotic response. In xenograft models, MPI-0479605 inhibits tumor growth, suggesting that drugs targeting Mps1 may have utility as novel cancer therapeutics. PMID- 21980131 TI - Direct role of adiponectin and adiponectin receptors in endometrial cancer: in vitro and ex vivo studies in humans. AB - Low adiponectin levels are an independent risk factor for and mediate the effect of obesity on endometrial cancer in epidemiology studies. The direct or indirect mechanisms underlying these findings remain to be elucidated. We first examined the expression of adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2) in normal human endometrium and in endometrial cancer tissues ex vivo. We then used KLE and RL95-2 human endometrial cancer cell lines in vitro to study relative expression of AdipoRs, to investigate the effect of adiponectin on activating intracellular signaling pathways, and to assess its potential to alter malignant properties. We report for the first time that the relative expression level of AdipoR1 is higher than AdipoR2 in human endometrial cancer tissue, but the expression of AdipoRs is not statistically different from nonneoplastic tissues. We also show for the first time in endometrial cancer cell lines in vitro that adiponectin suppresses endometrial cancer proliferation acting through AdipoRs. Adiponectin also increases the expression of the adaptor molecule LKB1, which is required for adiponectin-mediated activation of AMPK/S6 axis and modulation of cell proliferation, colony formation, adhesion, and invasion of KLE and RL95-2 cell lines. These novel mechanistic studies provide for the first time in vitro and ex vivo evidence for a causal role of adiponectin in endometrial cancer. PMID- 21980132 TI - Death receptor pathway activation and increase of ROS production by the triple epigenetic inhibitor UVI5008. AB - Deregulation of the epigenome is recognized as cause of cancer and epigenetic factors are receiving major attention as therapeutic targets; yet, the molecular mode of action of existing epi-drugs is largely elusive. Here, we report on the decryption of the mechanism of action of UVI5008, a novel epigenetic modifier, that inhibits histone deacetylases, sirtuins, and DNA methyltransferases. UVI5008 highly efficiently induces cancer cell-selective death in a variety of models and exerts its activities in several human tumor xenografts and genetic mouse models of human breast cancer in vivo. Its anticancer activity involves independent activation of death receptors and reactive oxygen species production. Importantly, UVI5008 action is not critically dependent on p53, Bcl-2 modifying factor, and/or TNF-related apoptosis-inducing ligand as cell death is efficiently induced in cells mutated or deficient for these factors limiting the risk of drug resistance development and maximizing its application spectrum. The simultaneous modulation of multiple (epigenetic) targets promises to open new avenues with unanticipated potential against cancer. PMID- 21980133 TI - Acquisition of resistance toward HYD1 correlates with a reduction in cleaved alpha4 integrin expression and a compromised CAM-DR phenotype. AB - We recently reported that the beta1 integrin antagonist, referred to as HYD1, induces necrotic cell death in myeloma cell lines as a single agent using in vitro and in vivo models. In this article, we sought to delineate the determinants of sensitivity and resistance toward HYD1-induced cell death. To this end, we developed an HYD1 isogenic resistant myeloma cell line by chronically exposing H929 myeloma cells to increasing concentrations of HYD1. Our data indicate that the acquisition of resistance toward HYD1 correlates with reduced levels of the cleaved alpha4 integrin subunit. Consistent with reduced VLA-4 (alpha4beta1) expression, the resistant variant showed ablated functional binding to fibronectin, VCAM-1, and the bone marrow stroma cell line HS-5. The reduction in binding of the resistant cell line to HS-5 cells translated to a compromised cell adhesion-mediated drug resistant phenotype as shown by increased sensitivity to melphalan- and bortezomib-induced cell death in the bone marrow stroma coculture model of drug resistance. Importantly, we show that HYD1 is more potent in relapsed myeloma specimens than newly diagnosed patients, a finding that correlated with alpha4 integrin expression. Collectively, these data indicate that this novel d-amino acid peptide may represent a good candidate for pursuing clinical trials in relapsed myeloma and in particular patients with high levels of alpha4 integrin. Moreover, our data provide further rationale for continued preclinical development of HYD1 and analogues of HYD1 for the treatment of multiple myeloma and potentially other tumors that home and/or metastasize to the bone. PMID- 21980134 TI - Cytoplasmic estrogen receptor in breast cancer. AB - PURPOSE: In addition to genomic signaling, it is accepted that estrogen receptor alpha (ERalpha) has nonnuclear signaling functions, which correlate with tamoxifen resistance in preclinical models. However, evidence for cytoplasmic ER localization in human breast tumors is less established. We sought to determine the presence and implications of nonnuclear ER in clinical specimens. EXPERIMENTAL DESIGN: A panel of ERalpha-specific antibodies (SP1, MC20, F10, 60c, and 1D5) was validated by Western blot and quantitative immunofluorescent (QIF) analysis of cell lines and patient controls. Then eight retrospective cohorts collected on tissue microarrays were assessed for cytoplasmic ER. Four cohorts were from Yale (YTMA 49, 107, 130, and 128) and four others (NCI YTMA 99, South Swedish Breast Cancer Group SBII, NSABP B14, and a Vietnamese Cohort) from other sites around the world. RESULTS: Four of the antibodies specifically recognized ER by Western and QIF analysis, showed linear increases in amounts of ER in cell line series with progressively increasing ER, and the antibodies were reproducible on YTMA 49 with Pearson correlations (r(2) values) ranging from 0.87 to 0.94. One antibody with striking cytoplasmic staining (MC20) failed validation. We found evidence for specific cytoplasmic staining with the other four antibodies across eight cohorts. The average incidence was 1.5%, ranging from 0 to 3.2%. CONCLUSIONS: Our data show ERalpha is present in the cytoplasm in a number of cases using multiple antibodies while reinforcing the importance of antibody validation. In nearly 3,200 cases, cytoplasmic ER is present at very low incidence, suggesting its measurement is unlikely to be of routine clinical value. PMID- 21980136 TI - Epigenetic alteration of PRKCDBP in colorectal cancers and its implication in tumor cell resistance to TNFalpha-induced apoptosis. AB - PURPOSE: PRKCDBP is a putative tumor suppressor in which alteration has been observed in several human cancers. We investigated expression and function of PRKCDBP in colorectal cells and tissues to explore its candidacy as a suppressor in colorectal tumorigenesis. EXPERIMENTAL DESIGN: Expression and methylation status of PRKCDBP and its effect on tumor growth were evaluated. Transcriptional regulation by NF-kappaB signaling was defined by luciferase reporter and chromatin immunoprecipitation assays. RESULTS: PRKCDBP expression was hardly detectable in 29 of 80 (36%) primary tumors and 11 of 19 (58%) cell lines, and its alteration correlated with tumor stage and grade. Promoter hypermethylation was commonly found in cancers. PRKCDBP expression induced the G(1) cell-cycle arrest and increased cellular sensitivity to various apoptotic stresses. PRKCDBP was induced by TNFalpha, and its level correlated with tumor cell sensitivity to TNFalpha-induced apoptosis. PRKCDBP induction by TNFalpha was disrupted by blocking NF-kappaB signaling while it was enhanced by RelA transfection. The PRKCDBP promoter activity was increased in response to TNFalpha, and this response was abolished by disruption of a kappaB site in the promoter. PRKCDBP delayed the formation and growth of xenograft tumors and improved tumor response to TNFalpha-induced apoptosis. CONCLUSIONS: PRKCDBP is a proapoptotic tumor suppressor which is commonly altered in colorectal cancer by promoter hypermethylation, and its gene transcription is directly activated by NF-kappaB in response to TNFalpha. This suggests that PRKCDBP inactivation may contribute to tumor progression by reducing cellular sensitivity to TNFalpha and other stresses, particularly under chronic inflammatory microenvironment. PMID- 21980137 TI - Agency as a psychoanalytic idea. AB - Competent agency is a basic assumption of psychoanalytic change. Yet as an aspect of health, personal agency has in the main been only intuitively addressed and remains clinically unsystematized. Here experience-near and observer-centered criteria are developed that assess a person-as-agent's competence in particular domains. These ideas, clinically illustrated, stand as an operational framework that helps thinking and talking about agency in everyday clinical events and psychoanalytic outcomes. Three specific criteria are proposed: reversibility, self-observation, and appropriateness. The first is descriptively polar; together the three apply to each given context of action. They can also serve to ground future research. In this regard, several empirical psychoanalytic studies of adults and children that exemplify measurable aspects of agency are reviewed. Once clinical markers of personal agency are articulated, it will not be necessary to resolve the free will debate: pragmatically, we need only put such distinctions to work. PMID- 21980135 TI - Lysosomal sequestration of sunitinib: a novel mechanism of drug resistance. AB - PURPOSE: Resistance to antiangiogenic tyrosine kinase inhibitors such as sunitinib is an important clinical problem, but its underlying mechanisms are largely unknown. We analyzed tumor sunitinib levels in mice and patients and studied sensitivity and resistance mechanisms to sunitinib. EXPERIMENTAL DESIGN: Intratumoral and plasma sunitinib concentrations in mice and patients were determined. Sunitinib exposure on tumor cell proliferation was examined. Resistant tumor cells were derived by continuous exposure and studied for alterations in intracellular sunitinib accumulation and activity. RESULTS: Intratumoral concentrations of sunitinib in mice and patients were 10.9 +/- 0.5 and 9.5 +/- 2.4 MUmol/L, respectively, whereas plasma concentrations were 10-fold lower, 1.0 +/- 0.1 and 0.3 +/- 0.1 MUmol/L, respectively. Sunitinib inhibited tumor cell growth at clinically relevant concentrations in vitro, with IC(50) values of 1.4 to 2.3 MUmol/L. Continuous exposure to sunitinib resulted in resistance of 786-O renal and HT-29 colon cancer cells. Fluorescent microscopy revealed intracellular sunitinib distribution to acidic lysosomes, which were significantly higher expressed in resistant cells. A 1.7- to 2.5-fold higher sunitinib concentration in resistant cells was measured because of increased lysosomal sequestration. Despite the higher intracellular sunitinib accumulation, levels of the key signaling p-Akt and p-ERK 1/2 were unaffected and comparable with untreated parental cells, indicating reduced effectiveness of sunitinib. CONCLUSION: We report that sunitinib inhibits tumor cell proliferation at clinically relevant concentrations and found lysosomal sequestration to be a novel mechanism of sunitinib resistance. This finding warrants clinical evaluation whether targeting lysosomal function will overcome sunitinib resistance. PMID- 21980138 TI - Suttie's influence on Fairbairn's object relations theory. AB - It is suggested here that Ian Suttie influenced W. R. D. Fairbairn directly through a 1939 reprint of his The Origins of Love and Hate, a heavily underlined copy of which was found by the author in Fairbairn's library in the University of Edinburgh Library Special Collections in October 2009. Underlined sections of the book are compared with significant aspects of Fairbairn's post-1940 theorizing, and the similarities are argued to be due to Fairbairn's adopting many of the underlying attitudes and ideas that Suttie developed. This leaves Fairbairn's structural theory, which he began to develop as a rational reconstruction of Freud's structural theory as early as 1927, dependent in part on such theory but independent of direct influence by Suttie. It is argued that Suttie's importance vis-a-vis British object relations thinking needs to be reassessed. PMID- 21980139 TI - "The noise monitor": a developmental perspective on verbal and nonverbal meaning making in psychoanalysis. AB - This paper discusses a contribution of developmental theory to the psychoanalytic concept of "the talking cure." The developmental theory presented is the dyadic expansion of consciousness model (Tronick 2007), a model consistent with the principles of nonlinear systems theory. The concept of "polysemic bundles" as a way of understanding the multiple simultaneous meaning-making processes occurring in dyadic communication is introduced. The theoretical discussion--focused primarily on the analysis of children--is illustrated with descriptions of videotaped sequences from the first session in the analysis of a five-year-old boy. The relevance of these insights to the analytic treatment of adults is then considered. PMID- 21980140 TI - Dave Eggers's a heartbreaking work of staggering genius: memoir as a "pain-relief device". AB - Dave Eggers's memoir is an important addition to the tradition of autobiography in America, and offers significant contributions to our understanding of creativity, sublimation, and the psychology of the memoir-writing process. A Heartbreaking Work of Staggering Genius is really two books--an autobiographical narrative about unbearable suffering, and a book of psychoanalytic commentary on the challenges of writing a memoir about catastrophic loss and trauma. The main narrative suggests the psychological resilience it takes to contain unbearable suffering. The metanarrative renders transparent the mind of someone who is both remembering his losses and constantly reflecting upon the process of writing about them. Eggers's identification with authorship, rather than bereavement or traumatization, may have played an important role in containing his affect and his sense of self when the heartbreaking events were originally unfolding. But a price is paid when a son uses his art to construct a new identity as an author- unconscious conflicts, primitive affect, anxieties about failing, as well as guilt about succeeding--consequences often missed by readers. Heartbreaking is a palimpsest, a story about story-telling superimposed on tales of death and survival, but its messages will be missed unless all its parts are preserved when being read or studied. PMID- 21980142 TI - Arabidopsis heterotrimeric G-protein regulates cell wall defense and resistance to necrotrophic fungi. AB - The Arabidopsis heterotrimeric G-protein controls defense responses to necrotrophic and vascular fungi. The agb1 mutant impaired in the Gbeta subunit displays enhanced susceptibility to these pathogens. Gbeta/AGB1 forms an obligate dimer with either one of the Arabidopsis Ggamma subunits (gamma1/AGG1 and gamma2/AGG2). Accordingly, we now demonstrate that the agg1 agg2 double mutant is as susceptible as agb1 plants to the necrotrophic fungus Plectosphaerella cucumerina. To elucidate the molecular basis of heterotrimeric G-protein-mediated resistance, we performed a comparative transcriptomic analysis of agb1-1 mutant and wild-type plants upon inoculation with P. cucumerina. This analysis, together with metabolomic studies, demonstrated that G-protein-mediated resistance was independent of defensive pathways required for resistance to necrotrophic fungi, such as the salicylic acid, jasmonic acid, ethylene, abscisic acid, and tryptophan-derived metabolites signaling, as these pathways were not impaired in agb1 and agg1 agg2 mutants. Notably, many mis-regulated genes in agb1 plants were related with cell wall functions, which was also the case in agg1 agg2 mutant. Biochemical analyses and Fourier Transform InfraRed (FTIR) spectroscopy of cell walls from G-protein mutants revealed that the xylose content was lower in agb1 and agg1 agg2 mutants than in wild-type plants, and that mutant walls had similar FTIR spectratypes, which differed from that of wild-type plants. The data presented here suggest a canonical functionality of the Gbeta and Ggamma1/gamma2 subunits in the control of Arabidopsis immune responses and the regulation of cell wall composition. PMID- 21980143 TI - A novel protein RLS1 with NB-ARM domains is involved in chloroplast degradation during leaf senescence in rice. AB - Leaf senescence, a type of programmed cell death (PCD) characterized by chlorophyll degradation, is important to plant growth and crop productivity. It emerges that autophagy is involved in chloroplast degradation during leaf senescence. However, the molecular mechanism(s) involved in the process is not well understood. In this study, the genetic and physiological characteristics of the rice rls1 (rapid leaf senescence 1) mutant were identified. The rls1 mutant developed small, yellow-brown lesions resembling disease scattered over the whole surfaces of leaves that displayed earlier senescence than those of wild-type plants. The rapid loss of chlorophyll content during senescence was the main cause of accelerated leaf senescence in rls1. Microscopic observation indicated that PCD was misregulated, probably resulting in the accelerated degradation of chloroplasts in rls1 leaves. Map-based cloning of the RLS1 gene revealed that it encodes a previously uncharacterized NB (nucleotide-binding site)-containing protein with an ARM (armadillo) domain at the carboxyl terminus. Consistent with its involvement in leaf senescence, RLS1 was up-regulated during dark-induced leaf senescence and down-regulated by cytokinin. Intriguingly, constitutive expression of RLS1 also slightly accelerated leaf senescence with decreased chlorophyll content in transgenic rice plants. Our study identified a previously uncharacterized NB-ARM protein involved in PCD during plant growth and development, providing a unique tool for dissecting possible autophagy-mediated PCD during senescence in plants. PMID- 21980145 TI - Association between adolescent marriage and intimate partner violence: a study of young adult women in Bangladesh. AB - This study explores the association between adolescent marriage and intimate partner violence (IPV) among young adult women using 2007 Bangladesh Demographic Health Survey data. The analyses are restricted to young women 20 to 24 years old. Logistic regression analyses are constructed to estimate the odds ratios and 95% confidence intervals for the association between adolescent marriage and IPV in the past year. RESULTS: show that there is a strong significant relationship between adolescent marriage and experience of physical IPV in the past year among this population. Association between sexual IPV and adolescent marriage is insignificant. Adolescent marriage puts women at increased risk of physical IPV into their young adult period. Government agencies need to enforce existing law on the minimum age at marriage to reduce IPV among adolescent and young adult girls. PMID- 21980144 TI - The role of tumour necrosis factor-alpha and tumour necrosis factor receptor signalling in inflammation-associated systemic genotoxicity. AB - Chronic inflammatory diseases are characterised by systemically elevated levels of tumour necrosis factor (TNF)-alpha, a proinflammatory cytokine with pleiotropic downstream effects. We have previously demonstrated increased genotoxicity in peripheral leukocytes and various tissues in models of intestinal inflammation. In the present study, we asked whether TNF-alpha is sufficient to induce DNA damage systemically, as observed in intestinal inflammation, and whether tumour necrosis factor receptor (TNFR) signalling would be necessary for the resultant genotoxicity. In the wild-type mice, 500 ng per mouse of TNF-alpha was sufficient to induce DNA damage to multiple cell types and organs 1-h post administration. Primary splenic T cells manifested TNF-alpha-induced DNA damage in the absence of other cell types. Furthermore, TNFR1(-/-)TNFR2(-/-) mice demonstrated decreased systemic DNA damage in a model of intestinal inflammation and after TNF-alpha injection versus wild-type mice, indicating the necessity of TNFR signalling. Nuclear factor (NF)-kappaB inhibitors were also able to decrease damage induced by TNF-alpha injection in wild-type mice. When TNF-alpha administration was combined with interleukin (IL)-1beta, another proinflammatory cytokine, DNA damage persisted for up to 24 h. When combined with IL-10, an anti inflammatory cytokine, decreased genotoxicity was observed in vivo and in vitro. TNF-alpha/TNFR-mediated signalling is therefore sufficient and plays a large role in mediating DNA damage to various cell types, subject to modulation by other cytokines and their mediators. PMID- 21980146 TI - Urban-rural and socioeconomic variations in the knowledge of STIs and AIDS among Bangladeshi adolescents. AB - This study used data from the Bangladesh Adolescents Survey 2005 to identify socioeconomic and urban-rural determinants of knowledge regarding sexually transmitted infections (STIs) including HIV/AIDS transmission. A cluster sampling of 11 986 adolescents was conducted from April to August 2005. Data were analyzed using SPSS applying principle component analysis, multivariate logistic regression analysis, and prevalence ratios (PRs) with 95% confidence intervals (CIs). Overall knowledge of transmission of STIs was poor (4.5%), showing urban adolescents having twice the knowledge of rural adolescents (PR = 1.9; 95% CI = 1.6-2.2). HIV/AIDS knowledge level was high (68%), with a 40% higher knowledge among urban adolescents (PR = 1.4; 95% CI = 1.3-1.4). Probability of knowledge of STIs and HIV/AIDS transmission was lowest in 12- to 14-year-old uneducated female household workers of the poorest socioeconomic status in rural settings (0.0002 and 0.064, respectively). The urban-rural factor was more important than the socioeconomic factor. Health promotion and education programs can play an important role in improving the sexual reproductive health knowledge situation. PMID- 21980147 TI - Cerebellar dysfunction in multiple sclerosis: in the blink of an eye. PMID- 21980148 TI - The impact of environmental infections (parasites) on MS activity. AB - MS incidence has significantly increased during the second half of the 20th century, generating considerable interest in analyzing the basis for this rise in the developed world. Particular emphasis is being placed on the role infections might play in exacerbating or preventing disease onset. Epidemiological data suggest that improvement in sanitation conditions and reduced exposure to infection might explain, at least in part, these changes. The hygiene hypothesis is not new and is currently used to explain the increasing incidence of allergies and other autoimmune diseases. Because helminths are powerful modulators of host immunity, some authors hypothesize that reduced parasite exposure due to improved hygiene conditions may favor MS development. We discuss epidemiological, experimental, clinical and molecular data supporting the protective role of helminthes against MS. Better understanding of host-parasite interactions caused by specific parasite molecules with immunomodulatory effects will help combat allergies and autoimmune disease without the price of untoward infection as a side-effect. PMID- 21980149 TI - Controversies in multiple sclerosis: a series of debates. PMID- 21980150 TI - The major cause of multiple sclerosis is environmental: genetics has a minor role -yes. PMID- 21980151 TI - The major cause of multiple sclerosis is environmental: genetics has a minor role -no. PMID- 21980152 TI - The major cause of multiple sclerosis is environmental: genetics has a minor role -commentary. PMID- 21980153 TI - Neural correlates of the antinociceptive effects of repetitive transcranial magnetic stimulation on central pain after stroke. AB - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) modulates central neuropathic pain in some patients after stroke, but the mechanisms of action are uncertain. OBJECTIVE: . The authors used diffusion tensor imaging (DTI) and functional MRI (fMRI) to evaluate the integrity of the thalamocortical tract (TCT) and the activation pattern of the pain network in 22 patients with poststroke central pain. METHODS: Each patient underwent daily 10-Hz rTMS sessions for 1000 pulses on 5 consecutive days over the hotspot for the first dorsal interosseus muscle. Pain severity was monitored using the Visual Analogue Scale (VAS). Mood was assessed by the Hamilton Depression Rating Scale. RESULTS: Clinical data from all participants along with the DTI and fMRI findings from 10 patients were analyzed. VAS scores decreased significantly, if modestly, following administration of rTMS in 14 responders, which lasted for 2 weeks after the intervention. Regression analysis showed a significant correlation between less initial depression and higher antalgic effect of rTMS. Integrity of the superior TCT in the ipsilesional hemisphere showed significant correlation with change of VAS score after rTMS. fMRI showed significantly decreased activity in the secondary somatosensory cortex, insula, prefrontal cortex, and putamen in rTMS responders, whereas no change was noted in nonresponders. CONCLUSION: . Mood may affect the modest antinociceptive effects of rTMS that we found, which may be mediated by the superior TCT through modulation of a distributed pain network. PMID- 21980154 TI - Seasonal variation in peritoneal dialysis-associated peritonitis: a multi-centre registry study. AB - BACKGROUND: The role of seasonal variation in peritoneal dialysis (PD)-related peritonitis has been limited to a few small single-centre studies. METHODS: Using all 6610 Australian patients receiving PD between 1 October 2003 and 31 December 2008, we evaluated the influence of seasons on peritonitis rates (Poisson regression) and outcomes (multivariable logistic regression). RESULTS: The overall rate of peritonitis was 0.59 episodes per patient-year of treatment. Using winter as the reference season, the peritonitis incidence rate ratios (95% confidence interval) for summer, autumn and spring were 1.02 (0.95-1.09), 1.01 (0.94-1.08) and 0.99 (0.92-1.06), respectively. Significant seasonal variations were observed in the rates of peritonitis caused by coagulase-negative Staphylococci (spring and summer peaks), corynebacteria (winter peak) and Gram negative organisms (summer and autumn peaks). There were trends to seasonal variations in fungal peritonitis (summer and autumn peaks) and pseudomonas peritonitis (summer peak). No significant seasonal variations were observed for other organisms. Peritonitis outcomes did not significantly vary according to season. CONCLUSIONS: Seasonal variation has no appreciable influence on overall PD peritonitis rates or clinical outcomes. Nevertheless, significant seasonal variations were observed in the rates of peritonitis due to specific microorganisms, which may allow institutions to more precisely target infection control strategies prior to higher risk seasons. PMID- 21980155 TI - Measuring the quality of end of life management in patients with advanced kidney disease: results from the pan-Thames renal audit group. AB - BACKGROUND: Despite a recent increased awareness of the need for quality End of Life (EOL) care for patients with advanced kidney disease, there is no established method for measuring or auditing outcomes relating to EOL care in this population. METHODS: We designed a one-page proforma, which was used to collect data on various aspects of EOL care relating to all deaths of patients on dialysis and patients dying on specialist renal wards, over a predefined 8-week period in 10 hospitals in London and South-East England. RESULTS: One hundred and thirty-eight deaths were recorded over the 8-week study period. The majority of patients (83%) were receiving maintenance haemodialysis prior to their terminal presentation. About 69% of deaths occurred during an in-patient hospital admission-of these, 36% were considered 'unexpected' and most quality markers of good EOL management were significantly less likely to be achieved in these patients, including use of palliative care strategies, good symptom control and overall quality of death. Thirty-six per cent of patients were from various ethnic minorities, and in this group, there was a trend towards lower use of palliative care pathways and lower rates of withdrawal from dialysis. CONCLUSIONS: This study confirms that it is possible to measure many important outcomes relating to quality of EOL care using a proforma completed at the time of death. Our findings suggest that many aspects of good EOL care are under achieved in our region. This, in part, is due to a failure to recognize the worsening trajectory of the deteriorating patient, resulting in missed opportunities for EOL care planning and appropriate symptom control. Our observations suggest that there is a need for improved education and training in this area, particularly in detection of the dying patient, the value of advance care planning and the utility of tools such as the Liverpool Care Pathway. PMID- 21980156 TI - Cardiovascular and renal outcome in recipients of kidney grafts from living donors: role of aortic stiffness. AB - BACKGROUND: Cardiovascular (CV) risk remains high in renal transplant patients despite a clear improvement conferred by transplantation. This risk is attributed mostly to recipient-related risk factors. Donor vascular characteristics, such as arterial stiffness, have been poorly investigated in this regard. METHODS: Recipients of living-related (n = 75) and living-unrelated (n = 20) kidney grafts were recruited at a mean time of 107 +/- 41 months after transplantation for baseline evaluation and follow-up for the occurrence of the following composite outcome: myocardial infarction, stroke, CV death, doubling of serum creatinine or development of end-stage renal disease (ESRD). At inclusion, recipients and their corresponding donors underwent complete history, physical examination, laboratory tests and non-invasive measurement of aortic pulse wave velocity (PWV). RESULTS: During a mean follow-up of 56 +/- 18 months, 20 recipients doubled their serum creatinine, of whom 16 reached ESRD, and 9 suffered of a new CV event (5 of which were fatal). Cox proportional hazards regression analysis showed that, in addition to recipient-related parameters, such as the presence of CV event and the estimated glomerular filtration rate at inclusion, donor aortic PWV was a strong and independent predictor of the composite recipient outcome. CONCLUSIONS: Donor large artery stiffness may predict recipient CV and graft outcome. This finding demonstrates the tight link that exists between the vascular system and the kidneys and suggests that donor contribution to recipient outcome goes beyond simple parameters like age, gender and even familial or non-familial donor type. PMID- 21980157 TI - Transcription of nephrin-Neph3 gene pair is synergistically activated by WT1 and NF-kappaB and silenced by DNA methylation. AB - BACKGROUND: Nephrin and Neph3 are homologous molecules expressed in the podocyte slit diaphragms that are essential for normal glomerular ultrafiltration. Nephrin and Neph3 genes form a bidirectional gene pair suggesting that they may share key features in their regulation. We investigated if nephrin and Neph3 genes have similar mechanisms in their transcriptional regulation focussing on transcription factor Wilms' tumour 1 (WT1) and nuclear factor-kappaB (NF-kappaB) and DNA methylation. METHODS: Transcriptional regulation of nephrin and Neph3 by WT1 and NF-kappaB was analysed by overexpression studies, reporter gene assay and chromatin immunoprecipitation using A293 cells and cultured podocytes. The interaction between WT1 and NF-kappaB was studied by co-immunoprecipitation. The effect of NF-kappaB activator tumour necrosis factor-alpha (TNF-alpha) with or without NF-kappaB pathway inhibitor (BAY 11-7082) on nephrin and Neph3 messenger RNA (mRNA) expression and on cellular distribution of NF-kappaB was determined by quantitative polymerase chain reaction (PCR) and immunostaining, respectively. The role of DNA methylation in regulating nephrin and Neph3 genes was studied by demethylating agent (5-aza-2'-deoxycytidine) treatment and quantitative PCR. RESULTS: WT1 and NF-kappaB interact with nephrin and Neph3 promoter and cooperatively regulate nephrin and Neph3. The cooperation was further supported by the physical interaction between WT1 and NF-kappaB. TNF-alpha increased nephrin and Neph3 mRNA expression and this effect was mediated by NF-kappaB. Furthermore, DNA methylation played a role in silencing nephrin and Neph3 expression in a cell-type and differentiation stage-dependent manner. CONCLUSION: These results provide novel insights into the transcriptional regulation of nephrin and Neph3 genes and indicate that nephrin and Neph3 share the same mechanisms in their regulation. PMID- 21980158 TI - Don't mind meat? The denial of mind to animals used for human consumption. AB - Many people like eating meat, but most are reluctant to harm things that have minds. The current three studies show that this dissonance motivates people to deny minds to animals. Study 1 demonstrates that animals considered appropriate for human consumption are ascribed diminished mental capacities. Study 2 shows that meat eaters are motivated to deny minds to food animals when they are reminded of the link between meat and animal suffering. Finally, Study 3 provides direct support for our dissonance hypothesis, showing that expectations regarding the immediate consumption of meat increase mind denial. Moreover, this mind denial in turn reduces negative affect associated with dissonance. The findings highlight the role of dissonance reduction in facilitating the practice of meat eating and protecting cultural commitments. PMID- 21980159 TI - The push and pull of temptation: the bidirectional influence of temptation on self-control. AB - This article examines how people respond to the emergence of temptation in their environment. Three studies demonstrated that how people respond to temptation depends critically on their visceral state--whether or not they are actively experiencing visceral drives such as hunger, drug craving, or sexual arousal. We found that when people were in a "cold," nonvisceral state, the presence of temptation prompted cognition to support self-control. However, when people were in a "hot," visceral state, temptation prompted the same cognitive processes to support impulsive behavior. Study 1 examined how heterosexual men's level of sexual arousal influences their attention to attractive women. Study 2 examined whether satiated and craving smokers would engage in motivated reasoning in order to dampen (or enhance) the appeal of smoking when confronted with the temptation to smoke. Study 3 tested the boundaries of the interaction between visceral state and temptation. PMID- 21980161 TI - Pollinator-mediated gene flow fosters genetic variability in a narrow alpine endemic, Abronia alpina (Nyctaginaceae). AB - PREMISE OF THE STUDY: For rare and endemic plants that exist in small, isolated habitats, natural selection is expected to favor self-compatibility, which can result in low genetic diversity due to inbreeding and genetic drift. Using Abronia alpina, a rare alpine endemic of the California Floristic Province, we demonstrate that there are exceptions to these predictions. METHODS: We present the results of both a pollination experiment and a genetic study using AFLPs (amplified fragment length polymorphisms). Using controlled hand-pollination and pollinator observations, we examined the breeding system, pollination ecology, and mechanism for self-incompatibility in A. alpina. KEY RESULTS: Abronia alpina exhibits an allogamous mating system with probable self-incompatibility resulting from limited growth of pollen tubes originating from self-pollination. Only xenogamous crosses and open-pollinated controls produced seed, and only xenogamous crosses produced pollen tubes that reached the ovary. The molecular study shows that A. alpina has substantial genetic diversity for a rare, endemic species, evidenced by the high percentage of polymorphic loci and average expected heterozygosity. Gene flow among subpopulations, as inferred from AFLP markers, appears to be substantial, although the Kern River is an important physical barrier. CONCLUSIONS: Our results indicate that A. alpina is dependent on insects for both seed production and the maintenance of genetic diversity. This finding suggests that pollinators may be crucial to the long-term adaptive potential of rare, endemic plants and that conservation of rare endemics is, in part, dependent on community-level interactions such as plant-pollinator mutualisms. PMID- 21980160 TI - Descriptive epidemiology of CNS tumors in France: results from the Gironde Registry for the period 2000-2007. AB - An increase in the incidence of CNS tumors has been observed in many countries in the last decades. The reality of this trend has been much debated, as it has happened during a period when computer-assisted tomography and MRI have dramatically improved the detection of these tumors. The Gironde CNS Tumor Registry provides here the first data on CNS tumor incidence and trends in France for all histological types, including benign and malignant tumors, for the period 2000-2007. Incidence rates were calculated globally and for each histological subtype. For trends, a piecewise log-linear model was used. The overall annual incidence rate was found to be 17.6/100 000. Of this rate, 7.9/100 000 were neuroepithelial tumors and 6.0/100 000 were meningiomas. An overall increase in CNS tumor incidence was observed from 2000 to 2007, with an annual percent change (APC) of +2.33%, which was explained mainly by an increase in the incidence of meningiomas over the 8-year period (APC = +5.4%), and also more recently by an increase in neuroepithelial tumors (APC = +7.45% from 2003). The overall increase was more pronounced in women and in the elderly, with an APC peaking at +24.65% in subjects 85 and over. The increase in the incidence rates we observed may have several explanations: not only improvements in registration, diagnosis, and clinical practice, but also changes in potential risk factors. PMID- 21980162 TI - Convergent evolution of a symbiotic duet: the case of the lichen genus Polychidium (Peltigerales, Ascomycota). AB - PREMISE OF THE STUDY: Thallus architecture has long been a powerful guide for classifying lichens and has often trumped photobiont association and ascomatal type, but the reliability of these characters to predict phylogenetic affinity has seldom been tested. The cyanolichen genus Polychidium unites species that have strikingly similar gross morphology but consort with different photobiont genera. If Polychidium were found to be monophyletic, photobiont switching among closely related species would be suggested. If, however, species were found to arise in different lineages, a convergent body plan and ascomatal type evolution would be inferred. METHODS: We tested the monophyly of Polychidium with a multilocus phylogeny based on nuclear and mitochondrial sequence data from all known Peltigeralean families and reconstructed ancestral states for specific thallus architecture and ascomatal ontogeny types relative to Polychidium and other clades. KEY RESULTS: We found that Polychidium consists of two species groups that arose independently in different suborders within the Peltigerales, associated with Nostoc and Scytonema photobionts, respectively. We infer from ancestral character state reconstruction that dendroid thallus architecture evolved independently in these two lineages. CONCLUSIONS: The independent development of similar dendroid thallus architecture in different fungal suborders with different photobionts represents a clear and previously overlooked example of convergent evolution in lichens. Our results also suggest a pattern of character state conservation, loss, and reversion in ascomatal ontogeny types, hitherto considered conserved traits useful for higher level ascomycete systematics. PMID- 21980163 TI - Vigna (Leguminosae) sensu lato: the names and identities of the American segregate genera. AB - PREMISE OF STUDY: The legume genus Vigna and close relatives have highly elaborated floral morphologies that involve the coiling, bending, and intricate connection of flower parts. Banners, levers, platforms, and pumps have evolved that attract pollinators and then manipulate their movement. Given this three dimensional floral complexity, the taxonomy of Vigna and relatives has been confounded by the study of mostly two-dimensional museum specimens. A molecular phylogenetic analysis was undertaken in the effort to resolve long-standing taxonomic questions centered on floral morphology. METHODS: The phylogenetic analysis included cpDNA trnK and nuclear ribosomal ITS/5.8S (ITS) sequence variation. The American species were comprehensively sampled and outgroups included Old World relatives. KEY RESULTS: The trnK and ITS data analyses concurred in resolving six well-supported clades of American Vigna that are most closely related to other American genera: Dolichopsis, Macroptilium, Mysanthus, Oryxis, Oxyrhynchus, Phaseolus, Ramirezella, and Strophostyles. These 14 American clades ranked here as genera are resolved as sister to a clade comprising the mainly Old World species of Vigna. CONCLUSIONS: American Vigna clades were reassigned to the genera Ancistrotropis, Cochliasanthus, Condylostylis, Leptospron, Sigmoidotropis, and the newly described Helicotropis. Vigna sensu stricto in the Americas now includes relatively few and mostly pantropical species. Elaborate floral asymmetries are readily used to apomorphically diagnose nearly all of the American genera. The age estimates of the extant diversification of the American and its Old World sister clade are approximately coeval at ca. 6-7 million yr, which belies much greater floral variation in the Americas. PMID- 21980164 TI - Isolation and characterization of microsatellite markers for Dipteronia dyerana (Sapindaceae), an endangered endemic species in China. AB - PREMISE OF THE STUDY: Microsatellite markers were developed for Dipteronia dyerana, an endangered endemic species in China, to study the population genetics of this species. METHODS AND RESULTS: Using the Fast Isolation by AFLP of Sequences Containing repeats (FIASCO) protocol, 12 microsatellite markers that were successfully amplified showed polymorphism when tested on 31 individuals from two populations in the counties of Wenshan and Mengzi. Overall, the number of alleles per locus ranged between seven and 25, with an average of 12.3. Nine of these markers were able to be amplified in D. sinensis. CONCLUSIONS: These microsatellite markers should facilitate further studies on the population genetics and the reproductive ecology of Dipteronia. PMID- 21980165 TI - Development and characterization of microsatellite markers for Hebanthe eriantha (Amaranthaceae). AB - PREMISE OF THE STUDY: Hebanthe eriantha (Amaranthaceae) is extensively collected and used in folk medicine. Microsatellite markers were developed and characterized to investigate the genetic structure and diversity of germplasm collections of this species. METHODS AND RESULTS: Eleven highly polymorphic microsatellite markers were developed. The number of alleles observed for each locus ranged from two to eight. The observed and expected heterozygosities ranged from 0.000 to 0.808 and 0.455 to 0.851, respectively. CONCLUSIONS: These results show the utility of microsatellite loci for studies of population genetics in H. eriantha, which are important for the future conservation and cultivation of this medicinal species. PMID- 21980166 TI - Thirteen microsatellites developed by SSR-enriched pyrosequencing for Solanum rostratum (Solanaceae) and related species. AB - PREMISE OF THE STUDY: Microsatellite markers were developed using second generation sequencing in Solanum rostratum as a tool to study the reproductive biology and genetic structure of this invasive species. METHODS AND RESULTS: Thirteen microsatellites were successfully discovered and amplified in a single multiplexed PCR. All loci showed genetic variation in S. rostratum. Cross amplification in five closely related taxa was successful for a subset of loci. CONCLUSIONS: The set of 13 microsatellite markers developed here provides a time effective and cost-effective genetic tool to study the reproductive biology of S. rostratum. The demonstrated transferability of the PCR multiplex to related taxa also highlights its usefulness for evolutionary studies across Solanum sect. Androceras. PMID- 21980167 TI - Long-term biological variation of serum protein electrophoresis M-spike, urine M spike, and monoclonal serum free light chain quantification: implications for monitoring monoclonal gammopathies. AB - BACKGROUND: We analyzed serial data in patients with clinically stable monoclonal gammopathy to determine the total variation of serum M-spikes [measured with serum protein electrophoresis (SPEP)], urine M-spikes [measured with urine protein electrophoresis (UPEP)], and monoclonal serum free light chain (FLC) concentrations measured with immunoassay. METHODS: Patients to be studied were identified by (a) no treatment during the study interval, (b) no change in diagnosis and <5 g/L change in serum M-spike over the course of observation; (c) performance of all 3 tests (SPEP, UPEP, FLC immunoassay) in at least 3 serial samples that were obtained 9 months to 5 years apart; (d) serum M-spike >=10 g/L, urine M-spike >=200 mg/24 h, or clonal FLC >=100 mg/L. The total CV was calculated for each method. RESULTS: Among the cohort of 158 patients, 90 had measurable serum M-spikes, 25 had urine M-spikes, and 52 had measurable serum FLC abnormalities. The CVs were calculated for serial SPEP M-spikes (8.1%), UPEP M spikes (35.8%), and serum FLC concentrations (28.4%). Combining these CVs and the interassay analytical CVs, we calculated the biological CV for the serum M-spike (7.8%), urine M-spike (35.5%), and serum FLC concentration (27.8%). CONCLUSIONS: The variations in urine M-spike and serum FLC measurements during patient monitoring are similar and are larger than those for serum M-spikes. In addition, in this group of stable patients, a measurable serum FLC concentration was available twice as often as a measurable urine M-spike. PMID- 21980168 TI - Urinary excretion kinetics of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and its phase I and phase II metabolites in humans following controlled MDMA administration. AB - BACKGROUND: 3,4-Methylendioxymethamphetamine (MDMA) is excreted inhuman urine as unchanged drug and phase I and II metabolites. Previous urinary excretion studies after controlled oral MDMA administration have been performed only after conjugate cleavage. Therefore, we investigated intact MDMA glucuronide and sulfate metabolite excretion. METHODS: We used LC-high-resolution MS and GC-MS to reanalyze blind urine samples from 10 participants receiving 1.0 or 1.6 mg/kg MDMA orally. We determined median C(max),t(max), first and last detection times, and total urinary recovery; calculated ratios of sulfates and glucuronides; and performed in vitro-in vivo correlations. RESULTS: Phase II metabolites of 3,4 dihydroxymethamphetamine (DHMA),4-hydroxy-3-methoxymethamphetamine (HMMA),3,4 dihydroxyamphetamine (DHA), and 4-hydroxy-3-methoxyamphetamine were identified, although only DHMA sulfates, HMMA sulfate, and HMMA glucuronide had substantial abundance. Good correlation was observed for HMMA measured after acid hydrolysis and the sum of unconjugated HMMA, HMMA glucuronide, and HMMA sulfate (R(2) = 0.87). More than 90% of total DHMA and HMMA were excreted as conjugates. The analyte with the longest detection time was HMMA sulfate. Median HMMA sulfate/glucuronide and DHMA 3-sulfate/4-sulfate ratios for the first 24 h were 2.0 and 5.3, respectively, in accordance with previous in vitro calculations from human liver microsomes and cytosol experiments. CONCLUSIONS: Human MDMA urinary metabolites are primarily sulfates and glucuronides,with sulfates present in higher concentrations than glucuronides. This new knowledge may lead to improvements in urine MDMA and metabolite analysis in clinical and forensic toxicology, particularly for the performance of direct urine analysis. PMID- 21980169 TI - C-reactive protein induces release of both endothelial microparticles and circulating endothelial cells in vitro and in vivo: further evidence of endothelial dysfunction. AB - BACKGROUND: Inflammation is pivotal in atherosclerosis. A key early event in atherosclerosis is endothelial dysfunction. C-reactive protein (CRP), the prototypic marker of inflammation in humans, is a risk marker for cardiovascular disease, and there is mounting evidence to support its role in atherothrombosis. CRP has been shown to promote endothelial dysfunction both in vitro and in vivo. Emerging biomarkers of endothelial dysfunction include circulating endothelial cells (CECs) and endothelial microparticles (EMPs). However, there is a paucity of data examining the effect of CRP on CEC and EMP production in vitro and in vivo. METHODS: In this report, we treated human aortic endothelial cells (HAECs) with increasing concentrations of CRP (0-50 MUg/mL) or boiled CRP. We counted CECs and EMPs by flow cytometry. RESULTS: Although CRP treatment resulted in a significant increase in release of both CECs and EMPs, boiled CRP failed to have an effect. Pretreatment of HAECs with sepiapterin or diethylenetriamine NONOate, both of which preserve nitric oxide (NO), resulted in attenuation of CRP's effects on CECs and EMPs. CD32 and CD64 blocking antibodies but not CD16 antibody or lectin-like oxidized LDL receptor 1 small interfering RNA (LOX-1 siRNA) prevented CRP-induced production of CECs and EMPs. Furthermore, delivery of human CRP to Wistar rats compared with human serum albumin resulted in significantly increased CECs and EMPs, corroborating the in vitro findings. CONCLUSIONS: We provide novel data that CRP, via NO deficiency, promotes endothelial dysfunction by inducing release of CECs and EMPs, which are biomarkers of endothelial dysfunction. PMID- 21980170 TI - Searching for new biomarkers of renal diseases through proteomics. AB - BACKGROUND: Technological advances have resulted in a renaissance of proteomic studies directed at finding markers of disease progression, diagnosis, or responsiveness to therapy. Renal diseases are ideally suited for such research, given that urine is an easily accessible biofluid and its protein content is derived mainly from the kidney. Current renal prognostic markers have limited value, and renal biopsy remains the sole method for establishing a diagnosis. Mass spectrometry instruments, which can detect thousands of proteins at nanomolar (or even femtomolar) concentrations, may be expected to allow the discovery of improved markers of progression, diagnosis, or treatment responsiveness. CONTENT: In this review we describe the strengths and limitations of proteomic methods and the drawbacks of existing biomarkers, and provide an overview of opportunities in the field. We also highlight several proteomic studies of biomarkers of renal diseases selected from the plethora of studies performed. SUMMARY: It is clear that the field of proteomics has not yet fulfilled its promise. However, ongoing efforts to standardize sample collection and preparation, improve study designs, perform multicenter validations, and create joint industry-regulatory bodies offer promise for the recognition of novel molecules that could change clinical nephrology forever. PMID- 21980171 TI - Diabetes antibody standardization program: first proficiency evaluation of assays for autoantibodies to zinc transporter 8. AB - BACKGROUND: Zinc transporter 8 (ZnT8) is a recently identified major autoantigen in type 1 diabetes, and autoantibodies to ZnT8 (ZnT8A) are new markers for disease prediction and diagnosis. Here we report the results of the first international proficiency evaluation of ZnT8A assays by the Diabetes Antibody Standardization Program (DASP). METHODS: After a pilot workshop in 2007, an expanded ZnT8A workshop was held in 2009, with 26 participating laboratories from 13 countries submitting results of 63 different assays. ZnT8A levels were measured in coded sera from 50 patients with newly diagnosed type 1 diabetes and 100 blood donor controls. Results were analyzed comparing area under the ROC curve (ROC-AUC), sensitivity adjusted to 95% specificity (AS95), concordance of sample ZnT8A positive or negative designation, and autoantibody levels. RESULTS: ZnT8A radio binding assays (RBAs) based on combined immunoprecipitation of the 2 most frequent ZnT8 COOH-terminal domain polymorphic variants showed a median ROC AUC of 0.848 [interquartile range (IQR) 0.796-0.878] and a median AS95 of 70% (IQR 60%-72%). These RBAs were more sensitive than assays using as antigen either 1 ZnT8 variant only or chimeric constructs joining NH(2)- and COOH-terminal domains, assays based on immunoprecipitation and bioluminescent detection, or assays based on immunofluorescent staining of cells transfected with full-length antigen. CONCLUSIONS: The DASP workshop identified immunoprecipitation-based ZnT8A assays and antigen constructs that achieved both a high degree of sensitivity and specificity and were suitable for more widespread clinical application. PMID- 21980172 TI - Polyamines interact with hydroxyl radicals in activating Ca(2+) and K(+) transport across the root epidermal plasma membranes. AB - Reactive oxygen species (ROS) are integral components of the plant adaptive responses to environment. Importantly, ROS affect the intracellular Ca(2+) dynamics by activating a range of nonselective Ca(2+)-permeable channels in plasma membrane (PM). Using patch-clamp and noninvasive microelectrode ion flux measuring techniques, we have characterized ionic currents and net K(+) and Ca(2+) fluxes induced by hydroxyl radicals (OH(*)) in pea (Pisum sativum) roots. OH(*), but not hydrogen peroxide, activated a rapid Ca(2+) efflux and a more slowly developing net Ca(2+) influx concurrent with a net K(+) efflux. In isolated protoplasts, OH(*) evoked a nonselective current, with a time course and a steady-state magnitude similar to those for a K(+) efflux in intact roots. This current displayed a low ionic selectivity and was permeable to Ca(2+). Active OH(*)-induced Ca(2+) efflux in roots was suppressed by the PM Ca(2+) pump inhibitors eosine yellow and erythrosine B. The cation channel blockers gadolinium, nifedipine, and verapamil and the anionic channel blockers 5-nitro 2(3-phenylpropylamino)-benzoate and niflumate inhibited OH(*)-induced ionic currents in root protoplasts and K(+) efflux and Ca(2+) influx in roots. Contrary to expectations, polyamines (PAs) did not inhibit the OH(*)-induced cation fluxes. The net OH(*)-induced Ca(2+) efflux was largely prolonged in the presence of spermine, and all PAs tested (spermine, spermidine, and putrescine) accelerated and augmented the OH(*)-induced net K(+) efflux from roots. The latter effect was also observed in patch-clamp experiments on root protoplasts. We conclude that PAs interact with ROS to alter intracellular Ca(2+) homeostasis by modulating both Ca(2+) influx and efflux transport systems at the root cell PM. PMID- 21980173 TI - Gene expression biomarkers provide sensitive indicators of in planta nitrogen status in maize. AB - Over the last several decades, increased agricultural production has been driven by improved agronomic practices and a dramatic increase in the use of nitrogen containing fertilizers to maximize the yield potential of crops. To reduce input costs and to minimize the potential environmental impacts of nitrogen fertilizer that has been used to optimize yield, an increased understanding of the molecular responses to nitrogen under field conditions is critical for our ability to further improve agricultural sustainability. Using maize (Zea mays) as a model, we have characterized the transcriptional response of plants grown under limiting and sufficient nitrogen conditions and during the recovery of nitrogen-starved plants. We show that a large percentage (approximately 7%) of the maize transcriptome is nitrogen responsive, similar to previous observations in other plant species. Furthermore, we have used statistical approaches to identify a small set of genes whose expression profiles can quantitatively assess the response of plants to varying nitrogen conditions. Using a composite gene expression scoring system, this single set of biomarker genes can accurately assess nitrogen responses independently of genotype, developmental stage, tissue type, or environment, including in plants grown under controlled environments or in the field. Importantly, the biomarker composite expression response is much more rapid and quantitative than phenotypic observations. Consequently, we have successfully used these biomarkers to monitor nitrogen status in real-time assays of field-grown maize plants under typical production conditions. Our results suggest that biomarkers have the potential to be used as agronomic tools to monitor and optimize nitrogen fertilizer usage to help achieve maximal crop yields. PMID- 21980175 TI - Chimpanzees make mean-spirited, not prosocial, choices. PMID- 21980174 TI - Synthetic antisense oligodeoxynucleotides to transiently suppress different nucleus- and chloroplast-encoded proteins of higher plant chloroplasts. AB - Selective inhibition of gene expression by antisense oligodeoxynucleotides (ODNs) is widely applied in gene function analyses; however, experiments with ODNs in plants are scarce. In this work, we extend the use of ODNs in different plant species, optimizing the uptake, stability, and efficiency of ODNs with a combination of molecular biological and biophysical techniques to transiently inhibit the gene expression of different chloroplast proteins. We targeted the nucleus-encoded phytoene desaturase (pds) gene, encoding a key enzyme in carotenoid biosynthesis, the chlorophyll a/b-binding (cab) protein genes, and the chloroplast-encoded psbA gene, encoding the D1 protein. For pds and psbA, the in vivo stability of ODNs was increased by phosphorothioate modifications. After infiltration of ODNs into juvenile tobacco (Nicotiana benthamiana) leaves, we detected a 25% to 35% reduction in mRNA level and an approximately 5% decrease in both carotenoid content and the variable fluorescence of photosystem II. In detached etiolated wheat (Triticum aestivum) leaves, after 8 h of greening, the mRNA level, carotenoid content, and variable fluorescence were inhibited up to 75%, 25%, and 20%, respectively. Regarding cab, ODN treatments of etiolated wheat leaves resulted in an up to 59% decrease in the amount of chlorophyll b, a 41% decrease of the maximum chlorophyll fluorescence intensity, the cab mRNA level was reduced to 66%, and the protein level was suppressed up to 85% compared with the control. The psbA mRNA and protein levels in Arabidopsis (Arabidopsis thaliana) leaves were inhibited by up to 85% and 72%, respectively. To exploit the potential of ODNs for photosynthetic genes, we propose molecular design combined with fast, noninvasive techniques to test their functional effects. PMID- 21980176 TI - Edward (Ted) G. Jones, a neuroscientist and prolific neuroanatomist. PMID- 21980177 TI - Exercise and Parkinson's disease. PMID- 21980178 TI - Neurological picture: an intradural spinal tuberculoma mimicking a neurinoma. PMID- 21980179 TI - Contaminated cocaine and antineutrophil cytoplasmic antibody-associated disease. AB - BACKGROUND AND OBJECTIVES: Approximately 70% of illicit cocaine consumed in the United States is contaminated with levamisole. Most commonly used as a veterinary antihelminthic agent, levamisole is a known immunomodulating agent. Prolonged use in humans has been associated with cutaneous vasculitis and agranulocytosis. We describe the development of a systemic autoimmune disease associated with antineutrophil cytoplasmic antibodies (ANCA) in cocaine users. This complication appears to be linked to combined cocaine and levamisole exposure. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Cases were identified between March 2009 and November 2010 at Massachusetts General Hospital's ANCA laboratory. Cocaine exposure was identified from patient history in all cases. Medical records were reviewed for clinical presentation and for laboratory and diagnostic evaluation. RESULTS: Thirty cases of ANCA positivity associated with cocaine ingestion were identified. All had antimyeloperoxidase antibodies and 50% also had antiproteinase 3 antibodies. Complete clinical and laboratory data were available for 18 patients. Arthralgia (83%) and skin lesions (61%) were the most frequent complaints at presentation. Seventy-two percent of patients reported constitutional symptoms, including fever, night sweats, weight loss, or malaise. Four patients had biopsy-proven vasculitis. Two cases of acute kidney injury and three cases of pulmonary hemorrhage occurred. From the entire cohort of 30, two cases were identified during the first 3 months of our study period and nine cases presented during the last 3 months. CONCLUSIONS: We describe an association between the ingestion of levamisole-contaminated cocaine and ANCA-associated systemic autoimmune disease. Our data suggest that this is a potentially life threatening complication of cocaine use. PMID- 21980180 TI - A preponderance of evidence is sufficient. PMID- 21980181 TI - Serum erythropoietin level and mortality in kidney transplant recipients. AB - BACKGROUND AND OBJECTIVES: Posttransplant anemia is frequently reported in kidney transplant recipients and is associated with worsened patient survival. Similar to high erythropoiesis-stimulating agent requirements, resistance to endogenous erythropoietin may be associated with worse clinical outcomes in patients with ESRD. We examined the association between serum erythropoietin levels and mortality among kidney transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We collected sociodemographic, clinical, medical, and transplant history and laboratory data at baseline in 886 prevalent kidney transplant recipients (mean age 51 +/- 13 [SD] years, 60% men, 21% diabetics). A solid-phase chemiluminescent immunometric assay was used to measure serum erythropoietin. Cox proportional hazards regression was used to model the association between baseline serum erythropoietin levels and all-cause mortality risk. RESULTS: During the median 39-month follow-up, 99 subjects died. The median serum erythropoietin level was 10.85 U/L and hemoglobin was 137 +/- 16 g/L. Mortality rates were significantly higher in patients with higher erythropoietin levels (crude mortality rates in the highest to lowest erythropoietin tertiles were 51.7, 35.5, and 24.0 per 1000 patient-years, respectively [P = 0.008]). In unadjusted and also in adjusted Cox models each SD higher serum erythropoietin level significantly predicted all-cause mortality: HR(1SD increase) 1.22 and 1.28, respectively. In adjusted Cox models each SD higher serum erythropoietin/blood hemoglobin ratio also significantly predicted all-cause mortality: HR(1SD increase) 1.32. Serum erythropoietin predicted mortality in all analyzed subgroups. CONCLUSIONS: In this sample of prevalent kidney transplant recipients, higher serum erythropoietin levels were associated with increased mortality. PMID- 21980182 TI - Outcome differences across transplant centers: comparison of two methods for public reporting. AB - BACKGROUND AND OBJECTIVES: Reporting of standardized patient and graft survival rates by the Scientific Registry of Transplant Recipients (SRTR) aims to influence transplant centers to improve their performance. The methodology currently used is based on calculating observed-to-expected (OE) ratios for every center. Its accuracy has not been evaluated. Here, we compare the accuracy of standardized rates across centers with the OE method to an alternative generalized mixed-effect (ME) method. We also examine the association between public reporting and center outcome improvement. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Accuracy was measured as the root mean square error (RMSE) of the difference between standardized rates from one time period to standardized rates from a future time period. Data from the United States Renal Data System on all kidney transplants between January 1, 1996, and September 30, 2009 were analyzed. RESULTS: The ME method had a 0.5 to 4.5% smaller RMSE than the OE method. It also had a smaller range between the 5(th) and 95(th) percentile centers' standardized rates: 7.5% versus 10.5% for 3-year graft survival and 4.7% versus 7.9% for 3 year patient survival. The range did not change after the introduction of public reporting in 2001. In addition, 33% of all deaths and 29% of all graft failures in the 3 years after transplant could be attributed to differences across centers. CONCLUSIONS: The ME method can improve the accuracy of public reports on center outcomes. An examination of the reasons why public reports have not reduced differences across centers is necessary. PMID- 21980183 TI - Prevalence and correlates of multiple cardiovascular risk factors in children with chronic kidney disease. AB - BACKGROUND AND OBJECTIVES: Although prevalence of traditional cardiovascular risk factors (CVRF) has been described in children with CKD, the frequency with which these CVRF occur concomitantly and the clinical characteristics associated with multiple CVRF are unknown. This study determined the prevalence and characteristics of multiple CVRF in children in the Chronic Kidney Disease in Children study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using cross sectional data from first follow-up visits, we determined the prevalence of four CVRF: hypertension (casual BP >95(th) percentile or self-reported hypertension with concurrent use of anti-hypertensive medication), dyslipidemia (triglycerides >130 mg/dl, HDL <40 mg/dl, non-HDL >160 mg/dl, or use of lipid-lowering medication), obesity (BMI >95(th) percentile), and abnormal glucose metabolism (fasting glucose >110 mg/dl, insulin >20 MUIU/ml, or HOMA-IR >2.20, >3.61, or >3.64 for those at Tanner stage 1, 2 to 3, or 4 to 5, respectively) in 250 children (median age 12.2 years, 74% Caucasian, median iohexol-based GFR 45.2 ml/min per 1.73 m(2)). RESULTS: Forty-six percent had hypertension, 44% had dyslipidemia, 15% were obese, and 21% had abnormal glucose metabolism. Thirty nine percent, 22%, and 13% had one, two, and three or more CVRF, respectively. In multivariate ordinal logistic regression analysis, glomerular disease and nephrotic-range proteinuria were associated with 1.96 (95% confidence interval, 1.04 to 3.72) and 2.04 (95% confidence interval, 0.94 to 4.43) higher odds of having more CVRF, respectively. CONCLUSIONS: We found high prevalence of multiple CVRF in children with mild to moderate CKD. Children with glomerular disease may be at higher risk for future cardiovascular events. PMID- 21980184 TI - Acute kidney injury and chronic kidney disease: a work in progress. PMID- 21980185 TI - Echocardiographic parameters are independently associated with rate of renal function decline and progression to dialysis in patients with chronic kidney disease. AB - BACKGROUND AND OBJECTIVES: Cardiac abnormalities were frequently noted in patients with chronic kidney disease (CKD). This study is designed to assess whether echocardiographic parameters are associated with rate of renal function decline and progression to dialysis in CKD stage 3 to 5 patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This longitudinal study enrolled 415 patients. The renal end point was defined as commencement of dialysis. The change in renal function was measured by estimated GFR (eGFR) slope. RESULTS: Progression to dialysis was predicted by wide pulse pressure, low albumin, low hemoglobin, high calcium-phosphorous product, proteinuria, diuretics use, and concentric left ventricular hypertrophy (LVH) (hazard ratio, 2.03; 95% confidence interval [CI], 1.00 to 4.10; P = 0.05). The eGFR slope was negatively associated with total cholesterol, uric acid, proteinuria, diuretics use, and left atrial (LA) diameter (change in slope, -0.50; 95% CI, -0.89 to -0.11; P = 0.01) and positively associated with albumin and left ventricular ejection fraction (LVEF) (change in slope, 0.06; 95% CI, 0.03 to 0.08; P < 0.001). CONCLUSIONS: Our study in patients of CKD stage 3 to 5 demonstrated that concentric LVH was associated with progression to dialysis, and that increased LA diameter and decreased LVEF were associated with faster renal function decline. Echocardiography may help identify high-risk groups with progressive decline in renal function to dialysis and rapid progression of renal dysfunction in CKD stage 3 to 5 patients. PMID- 21980186 TI - Alignment of nephrology training with workforce, patient, and educational needs: an evidence based proposal. AB - BACKGROUND AND OBJECTIVES: Competency-based training programs focus on the product of training rather than the process with the desired attributes and skills set of the specialist directing the training program. These ideal skills and qualities have yet to be formally identified for nephrology training. The objectives of our study were: (1) to define the attributes of a "high quality" nephrologist from the perspectives of the trainer (nephrologist), trainee, and renal patient and (2) identify components and relative frequencies of nephrologists' work practice. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Four substudies were undertaken, utilizing a combined quantitative and qualitative approach: (1) a national nephrology workforce study, (2) in-depth interviews of nephrology patients, (3) in-depth interviews of nephrology trainees, and (4) in depth interviews of practicing nephrologists. RESULTS: Patients value good communication skills above other attributes. Nephrologists and trainees identify particular personal attributes, a holistic and evidence-based approach to patient care, and good clinical skills as paramount. Although nephrologists spend most of their time in clinical practice, substantial time is also spent in research, teaching, and administrative work. CONCLUSIONS: For the first time, an evidence based approach has been used to help define qualities desired in a practicing nephrologist. Along with training and assessment in clinical practice, this research supports nephrology training programs incorporating training in basic interventions, research skill acquisition, administration, and teaching. Training toward high standards in advanced communication and the maintenance of a holistic approach to patient care are necessary. PMID- 21980187 TI - Perceptual compression of visual space during eye-head gaze shifts. AB - In primates, inspection of a visual scene is typically interrupted by frequent gaze shifts, occurring at an average rate of three to five times per second. Perceptually, these gaze shifts are accompanied by a compression of visual space toward the saccade target, which may be attributed to an oculomotor signal that transiently influences visual processing. While previous studies of compression have focused exclusively on saccadic eye movements made with the head artificially immobilized, many brain structures involved in saccade generation also encode combined eye-head gaze shifts. Thus, in order to understand the interaction between gaze motor and visual signals, we studied perception during eye-head gaze shifts and found a powerful compression of visual space that was spatially directed toward the intended gaze (and not the eye movement) target location. This perceptual compression was nearly constant in duration across gaze shift amplitudes, suggesting that the signal that triggers compression is largely independent of the size and kinematics of the gaze shift. The spatial pattern of results could be captured by a model that involves interactions, on a logarithmic map of visual space, between two loci of neural activity that encode the gaze shift vector and visual stimulus position relative to the fovea. PMID- 21980188 TI - Color names, color categories, and color-cued visual search: sometimes, color perception is not categorical. AB - The relation between colors and their names is a classic case study for investigating the Sapir-Whorf hypothesis that categorical perception is imposed on perception by language. Here, we investigate the Sapir-Whorf prediction that visual search for a green target presented among blue distractors (or vice versa) should be faster than search for a green target presented among distractors of a different color of green (or for a blue target among different blue distractors). A. L. Gilbert, T. Regier, P. Kay, and R. B. Ivry (2006) reported that this Sapir Whorf effect is restricted to the right visual field (RVF), because the major brain language centers are in the left cerebral hemisphere. We found no categorical effect at the Green-Blue color boundary and no categorical effect restricted to the RVF. Scaling of perceived color differences by Maximum Likelihood Difference Scaling (MLDS) also showed no categorical effect, including no effect specific to the RVF. Two models fit the data: a color difference model based on MLDS and a standard opponent-colors model of color discrimination based on the spectral sensitivities of the cones. Neither of these models nor any of our data suggested categorical perception of colors at the Green-Blue boundary, in either visual field. PMID- 21980189 TI - Object features fail independently in visual working memory: evidence for a probabilistic feature-store model. AB - The world is composed of features and objects and this structure may influence what is stored in working memory. It is widely believed that the content of memory is object-based: Memory stores integrated objects, not independent features. We asked participants to report the color and orientation of an object and found that memory errors were largely independent: Even when one of the object's features was entirely forgotten, the other feature was often reported. This finding contradicts object-based models and challenges fundamental assumptions about the organization of information in working memory. We propose an alternative framework involving independent self-sustaining representations that may fail probabilistically and independently for each feature. This account predicts that the degree of independence in feature storage is determined by the degree of overlap in neural coding during perception. Consistent with this prediction, we found that errors for jointly encoded dimensions were less independent than errors for independently encoded dimensions. PMID- 21980190 TI - Mating system shifts on the trailing edge. AB - BACKGROUND: The trailing edges of species ranges are becoming a subject of increasing interest as the environment changes due to global warming. Trailing edge populations are likely to face extinction because of a decline in numbers and an inability to evolve new adaptations with sufficient speed. Discussions of character change in the trailing edge have focused on physiological, exomorphic and phenological traits. The mating pattern within populations has not been part of the discourse, in spite of the fact that the mating pattern may affect the ability of populations to respond to environmental change and to maintain their sizes. In this paper, the case is made that a substantial increase in self fertilization rates may occur via plastic responses to stress. SCOPE AND CONCLUSIONS: Small populations on the trailing edge are especially vulnerable to environmental change because of inadequate levels of cross-fertilization. Evidence is presented that a deficiency of cross-seed production is due to inadequate pollinator services and a paucity of self-incompatibility alleles within populations. Evidence also is presented that if plants are self compatible, self-fertilization may compensate in part for this deficiency through a stress-induced increase in levels of self-compatibility and stress-induced alterations in floral morphology that elevate self-pollination. Whereas increased self-fertility may afford populations the time to adapt to their changing environments, it can be concluded that increased selfing is not a panacea for the ills of environmental change, because it will lead to substantial reductions in genetic diversity, which may render adaptation unlikely. PMID- 21980191 TI - Dichogamy correlates with outcrossing rate and defines the selfing syndrome in the mixed-mating genus Collinsia. AB - BACKGROUND AND AIMS: How and why plants evolve to become selfing is a long standing evolutionary puzzle. The transition from outcrossing to highly selfing is less well understood in self-compatible (SC) mixed-mating (MM) species where potentially subtle interactions between floral phenotypes and the environment are at play. We examined floral morphological and developmental traits across an entire SC MM genus, Collinsia, to determine which, if any, predict potential autonomous selfing ability when pollinators are absent (AS) and actual selfing rates in the wild, s(m), and to best define the selfing syndrome for this clade. METHODS: Using polymorphic microsatellite markers, we obtained 30 population level estimates of s(m) across 19 Collinsia taxa. Species grand means for the timing of herkogamy (stigma-anther contact) and dichogamy (stigmatic receptivity, SR), AS, floral size, longevity and their genetic correlations were quantified for 22 taxa. KEY RESULTS: Species fell into discrete selfing and outcrossing groups based on floral traits. Loss of dichogamy defines Collinsia's selfing syndrome. Floral size, longevity and herkogamy also differ significantly between these groups. Most taxa have high AS rates (>80 %), but AS is uncorrelated with any measured trait. In contrast, s(m) is significantly correlated only with SR. High variance in s(m) was observed in the two groups. CONCLUSIONS: Collinsia species exhibit clear morphological and developmental traits diagnostic of 'selfing' or 'outcrossing' groups. However, many species in both the 'selfing' and the 'outcrossing' groups were MM, pointing to the critical influence of the pollination environment, the timing of AS and outcross pollen prepotency on s(m). Flower size is a poor predictor of Collinsia species' field selfing rates and this result may apply to many SC species. Assessment of the variation in the pollination environment, which can increase selfing rates in more 'outcrossing' species but can also decrease selfing rates in more 'selfing' species, is critical to understanding mating system evolution of SC MM taxa. PMID- 21980192 TI - Induced polyploidy dramatically increases the size and alters the shape of fruit in Actinidia chinensis. AB - BACKGROUND AND AIMS: Some otherwise promising selections of Actinidia chinensis (kiwifruit) have fruit that are too small for successful commercialization. We have therefore made the first detailed study in diploid kiwifruit of the effects of chromosome doubling induced by colchicine on fruit size, shape and crop loading. METHODS: Flow cytometric analysis of young leaves and chromosome analysis of flower buds and root tips was used to confirm the stability of induced autotetraploids. Fruit weight, size and crop load were measured in the third year after planting in the field and for three consecutive years. DNA fingerprinting was used to confirm the origin of the material. KEY RESULTS: There was a very significant increase in fruit size in induced autotetraploids of different genotypes of A. chinensis. With the commercially important diploid cultivar 'Hort16A', most regenerants, Type A plants, had fruit which were much the same shape as fruit of the diploid but, at the same fruit load, were much larger and heavier. Some regenerants, Type B plants, produced fruit similar to 'fasciated' fruit. Fruit of the autotetraploids induced from three female red fleshed A. chinensis selections were also 50-60 % larger than fruit of their diploid progenitors. The main increase in fruit dimensions was in their diameters. These improved fruit characteristics were stable over several seasons. CONCLUSIONS: Chromosome doubling has been shown to increase significantly fruit size in autotetraploid A. chinensis, highlighting the considerable potential of this technique to produce new cultivars with fruit of adequate size. Other variants with differently shaped fruit were also produced but the genetic basis of this variation remains to be elucidated. Autoploids of other Actinidia species with commercial potential may also show improved fruit characteristics, opening up many new possibilities for commercial development. PMID- 21980193 TI - Minimising critical organ irradiation in limited stage Hodgkin lymphoma: a dosimetric study of the benefit of involved node radiotherapy. AB - BACKGROUND: Chemotherapy plus radiotherapy is the standard of care for patients with limited stage Hodgkin lymphoma (HL). Radiotherapy is evolving from involved field radiotherapy (IFRT) to involved node radiotherapy (INRT) to decrease radiotherapy-related morbidity. In the absence of long-term toxicity data, dose volume metrics of organs at risk (OAR) provide a surrogate measure of toxicity risk. PATIENTS AND METHODS: Ten female patients with stage I-IIA supradiaphragmatic HL were randomly selected. All patients had pre-chemotherapy computerised tomography (CT) and CT-positron emission tomography staging. Using CT planning, three radiotherapy plans were produced per patient: (i) IFRT, (ii) INRT using parallel-opposed beams and (iii) INRT using volumetric modulated arc therapy (VMAT). Radiotherapy dose was 30.6 Gy in 1.8 Gy fractions. OAR evaluated were lungs, breasts, thyroid, heart and coronary arteries. RESULTS: Compared with IFRT, INRT significantly reduced mean doses to lungs (P < 0.01), breasts (P < 0.01), thyroid (P < 0.01) and heart (P < 0.01), on Wilcoxon testing. Compared with conventional INRT, VMAT improved dose conformality but increased low-dose radiation exposure to lungs and breasts. VMAT reduced the heart volume receiving 30 Gy (V30) by 85%. CONCLUSIONS: Reduction from IFRT to INRT decreased the volumes of lungs, breasts and thyroid receiving high-dose radiation, suggesting the potential to reduce long-term second malignancy risks. VMAT may be useful for patients with pre-existing heart disease by minimising further cardiac toxicity risks. PMID- 21980194 TI - Intracranial hemorrhage, outcome, and mortality after intra-arterial therapy for acute ischemic stroke in patients under oral anticoagulants. AB - BACKGROUND AND PURPOSE: Use of intravenous tissue-type plasminogen activator (IV tPA) for acute ischemic stroke is restricted to patients with an international normalized ratio (INR) less than 1.7. However, a recent study showed increased risk of symptomatic intracranial hemorrhage after IV tPA use in patients with oral anticoagulants (OAC) even with an INR less than 1.7. The present study assessed the risk of symptomatic intracranial hemorrhage, clinical outcome, and mortality after intra-arterial therapy (IAT) in patients with and without previous use of OAC. METHODS: Consecutive patients treated with IAT from December 1992 to October 2010 were included. Clinical outcome and mortality were assessed 90 days after stroke onset. Patients with and without previous use of OAC were compared. RESULTS: Overall, 714 patients were treated with IAT. Twenty-eight patients (3.9%) were under OAC at time of symptom onset. Median INR in the OAC group was 1.79 (interquartile range [IQR], 1.41-2.3) and 1.01 (IQR, 1.0-1.09; P<0.0001) in the group without OAC. Patients treated with OAC at admission underwent more often mechanical-only IAT than did patients without OAC (46.4% versus 12.8%; P<0.0001). Comparing patients with and without previous use of OAC, we did not find any statistical difference in the rate of symptomatic intracranial hemorrhage (7.1% versus 6.0%; P=0.80), unfavorable outcome (modified Rankin Scale score, 3-6; 67.9% versus 50.9%; P=0.11), and mortality (17.9% versus 21.6%; P=0.58). CONCLUSIONS: Previous use of OAC did not significantly increase the risk of symptomatic intracranial hemorrhage after IAT or the risk of unfavorable outcome and mortality 90 days after IAT. PMID- 21980195 TI - Long-term stimulation of neural progenitor cell migration after cortical ischemia in mice. AB - BACKGROUND AND PURPOSE: Cortical ischemia induces neural progenitor cell migration toward the injury site; however, whether these cells are capable of maintaining the migratory response for a longer period after injury remains uncertain. METHODS: We analyzed progenitor migration up to 1 year after induction of photothrombotic stroke to the mouse neocortex. Migrating progenitors identified as doublecortin positive cells (DCX+) were assessed using the immunohistochemistry and immunofluorescence. The thymidine analogues chlorodeoxyuridine and iododeoxyuridine were used to birth-date the progenitor cells. RESULTS: In the striatum, we detected elevated numbers of DCX+ cells up to 6 weeks postlesion. In the corpus callosum and the peri-infarct cortex (Ctx), DCX+ cell numbers were increased up to 1 year. The orientation of the migrating progenitors was mostly aligned with the corpus callosum fiber tract at all time points; however, in the Ctx, they aligned parallel to the infarct border. The injured cortex continuously receives new progenitors up to 1 year after lesion. Cells born after lesion did not become mature neurons, although a portion of the migrating progenitors showed initial signs of differentiation into neurons. CONCLUSIONS: Neural progenitors might have a role in brain plasticity after cortical stroke, especially considering the prolonged window of migratory responses of up to 1 year after stroke lesion. PMID- 21980196 TI - Epidemiology and outcomes of fever burden among patients with acute ischemic stroke. AB - BACKGROUND AND PURPOSE: Although fever following ischemic stroke is common and has been associated with poor patient outcomes, little is known about which aspects of fever (eg, frequency, severity, or duration) are most associated with outcomes. METHODS: We used data from a retrospective cohort of acute ischemic stroke patients who were admitted to 1 of 5 hospitals (1998-2003). A fever event was defined as a period with a temperature>=100.0 degrees F (37.8 degrees C). Fever burden was defined as the maximum temperature (Tmax) minus 100.0 degrees F, multiplied by the number of days with a fever. Fever burden (in degree-days) was categorized as low (0.1-2.0), medium (2.1-4.0), or high (>=4.0). Logistic regression was used to evaluate the adjusted association of any fever episode and fever burden with the combined outcome of in-hospital mortality or discharge to hospice. RESULTS: Among 1361 stroke patients, 483 patients (35.5%) had >=1 fever event. Among febrile patients, the median Tmax was 100.9 degrees F (range, 100.0 106.6 degrees F), 87% had <=2 events and median total fever days was 2. Patients with any fever event had higher combined outcome rates after adjusting for demographics, stroke severity, and clinical characteristics: adjusted odds ratio (aOR), 2.7 (95% CI, 1.6-4.4). Higher fever burden was also associated with the combined outcome: high burden aOR, 6.7 (95% CI, 3.6-12.7); medium burden aOR, 3.9 (95% CI, 1.9-8.2); and low burden aOR, 1.2 (95%CI, 0.6-2.3) versus no fever. CONCLUSIONS: This study confirms that poststroke fever occurs commonly and demonstrates that patients with high fever burden have a 6-fold increased odds of death or discharge to hospice. PMID- 21980197 TI - Representativeness of the Get With The Guidelines-Stroke Registry: comparison of patient and hospital characteristics among Medicare beneficiaries hospitalized with ischemic stroke. AB - BACKGROUND AND PURPOSE: Get With The Guidelines (GWTG)-Stroke is a large quality improvement-based registry of acute stroke; however, its generalizability is unclear. We used fee-for-service Medicare claims to ascertain the representativeness of ischemic stroke admissions in GWTG-Stroke. METHODS: All 228 815 ischemic stroke admissions aged >=65 years enrolled in GWTG-Stroke between April 2003 and December 2007 were linked to 926 756 unique fee-for-service Medicare patients with ischemic stroke (primary International Classification of Diseases, 9th Revision discharge code 434 or 436) from the same period. Patient characteristics and in-hospital outcomes were compared between the linked GWTG Stroke Medicare cohort and the remaining unlinked Medicare cohort. Characteristics of GWTG-Stroke hospitals were compared with non-GWTG-Stroke hospitals. RESULTS: A total of 144 344 of the 228,815 GWTG-Stroke admissions (63.1%) were successfully linked to the 926 756 Medicare ischemic stroke beneficiaries, leaving 782 412 unlinked Medicare patients. Differences in patient characteristics, including age, race, gender, and comorbidities, between the linked and unlinked Medicare cohorts were minimal. Length of stay and rate of discharge home were almost identical between the linked and unlinked groups; however, in-hospital mortality was slightly lower in the linked Medicare cohort (6.3%) compared with the unlinked cohort (7.0%). There were large differences in hospital characteristics between GWTG-Stroke and non-GWTG-Stroke hospitals; GWTG Stroke hospitals tended to be larger, urban, teaching centers. CONCLUSIONS: Despite substantial differences between GWTG-Stroke and non-GWTG-Stroke hospitals, Medicare beneficiaries with acute ischemic stroke entered in the GWTG Stroke program were similar to other Medicare beneficiaries. These data suggest that the Medicare-aged GWTG-Stroke ischemic stroke admissions are generally representative of the national fee-for-service Medicare ischemic stroke population. PMID- 21980198 TI - Influence of socioeconomic status on distance traveled and care after stroke. AB - BACKGROUND AND PURPOSE: Vital to maintaining an efficient delivery of services is an understanding of patient travel patterns during an acute ischemic stroke. Socioeconomic status may influence access to stroke care, including transportation and admission to different facility types. METHODS: We analyzed all acute ischemic stroke admissions between 2003 and 2007 through the Discharge Abstract Database, a national database containing patient-level sociodemographic, diagnostic, procedural, and administrative information across Canada. Socioeconomic status was defined in neighborhood quintiles according to Statistics Canada. Distances between patients and facilities were derived from postal codes. A principal diagnosis of ischemic stroke was identified using the International Classification of Diseases (versions 9 and 10). Analysis of variance and regression analyses were performed with adjustment for demographic characteristics. RESULTS: Admitted to acute care institutions were 243 410 patients with ischemic stroke. Mean patient age was 72.8 and 49.5% were male; 44.2% traveled beyond their closest center, amounting to an average 7.2 km additional distance traveled. Socioeconomic status quintile had minimal effect on travel patterns, with the lowest socioeconomic status accessing the closest center most frequently (odds ratio, 1.19; 95% confidence interval [CI], 1.13 1.16). Increased utilization of the closest hospital occurred with academic (odds ratio, 6.90; 95% CI, 6.69-7.11) or high-volume (odds ratio, 1.93; 95% CI, 1.88 1.98) facilities. Older patients (beta=0.28; 95% CI, 0.27-0.28), expert destination facility (beta=0.13; 95% CI, 0.12-0.14), and ambulance use increased travel beyond the closest center. CONCLUSIONS: Patients tend to choose care facilities based on hospital expertise; investment promoting improved regional facilities may be of greatest benefit to patients. Socioeconomic status has little bearing on travel patterns associated with stroke in Canada. These findings may assist in allocating funding to centers and improving patient care. PMID- 21980200 TI - Cerebral mast cells mediate blood-brain barrier disruption in acute experimental ischemic stroke through perivascular gelatinase activation. AB - BACKGROUND AND PURPOSE: Perivascularly positioned cerebral mast cells (MC) have been shown to participate in acute blood-brain barrier disruption and expansive brain edema following experimental transient cerebral ischemia. However, the underlying molecular mechanisms remain unknown. Because proteolytic gelatinase enzymes, matrix metalloproteinases (MMP)-2 and MMP-9, are thought to have a central role in compromising the integrity of the blood-brain barrier following ischemia, we examined whether cerebral MCs influence gelatinase activity in ischemic cerebral microvasculature. METHODS: Rats underwent 60 minutes of middle cerebral artery occlusion followed by 3-hour reperfusion, and were treated with a MC-stabilizing (cromoglycate), or MC-degranulating (compound 48/80) agent, or vehicle. Genetically manipulated, MC-deficient WsRc(Ws/Ws) rats and their wild type littermates (WT) underwent the same procedures. Cerebral edema and extravasation of Evans blue albumin were measured. Gelatinase activity was visualized by in situ zymography and was quantified with computerized high throughput image and data analysis. RESULTS: Activated MCs showed secretion of gelatinase-positive granules. Genetic MC deficiency decreased global gelatinase active area (-69%, compared with WT; P<0.001) and the mean gelatinase activity of the ischemic microvasculature (-57% compared with WT; P=0.002). MC stabilization with cromoglycate decreased the percentage of microvessels with high gelatinase activity (-36% compared with saline; P<0.05). Compound 48/80 showed increased area of in situ zymography activity in the ischemic lesion (+55% compared with saline; P<0.001). Microvascular gelatinase activity correlated with brain swelling (r=0.84; P<0.001; and r=0.61; P=0.02). CONCLUSIONS: Our data demonstrate that cerebral MCs participate in regulation of acute microvascular gelatinase activation and consequent blood-brain barrier disruption following transient cerebral ischemia. PMID- 21980199 TI - Sphingosine kinase 2 mediates cerebral preconditioning and protects the mouse brain against ischemic injury. AB - BACKGROUND AND PURPOSE: Cerebral preconditioning provides insights into endogenous mechanisms that protect the brain from ischemic injury. Hypoxia and the anesthetic isoflurane are powerful preconditioning agents. Recent data show that sphingosine 1-phosphate receptor stimulation improves outcome in rodent models of stroke. Endogenous sphingosine 1-phosphate levels are controlled by the expression and activity of sphingosine kinases (SPK). We hypothesize that SPK upregulation mediates preconditioning induced by isoflurane and hypoxia and reduces ischemic injury. METHODS: Male wild-type C57BL/J, SPK1(-/-) and SPK2(-/-) mice were exposed to isoflurane or hypoxia preconditioning before transient middle cerebral artery occlusion. Infarct volume and neurological outcome were measured 24 hours later. SPK inhibitors (SKI-II and ABC294640) were used to test the involvement of SPK2. Expressions of SPK1, SPK2, and hypoxia-inducible factor 1alpha were determined. Primary cultures of mouse cortical neurons were exposed to isoflurane before glutamate- or hydrogen peroxide-induced cell death. RESULTS: Isoflurane preconditioning and hypoxia preconditioning significantly reduced infarct volume and improved neurological outcome in wild-type and SPK1(-/-) mice but not in SPK2(-/-) mice. Pretreatment with SKI-II or ABC294640 abolished the isoflurane preconditioning-induced tolerance. Western blot showed a rapid and sustained increase in SPK2 level, whereas SPK1 level was similar between preconditioned mice and controls. Hypoxia-inducible factor 1alpha was upregulated in wild-type isoflurane-preconditioned mice but not in SPK2(-/-). Isoflurane preconditioning protected primary neurons against cell death, which was abolished in ABC294640-treated cells. CONCLUSIONS: Applying genetic and pharmacological approaches, we demonstrate that neuronal SPK2 isoform plays an important role in cerebral preconditioning. PMID- 21980201 TI - Improving outcomes after stroke by LEAPS (Locomotor Experience Applied Post Stroke) and bounds. PMID- 21980202 TI - Cerebral blood flow is the optimal CT perfusion parameter for assessing infarct core. AB - BACKGROUND AND PURPOSE: CT perfusion (CTP) is widely and rapidly accessible for imaging acute ischemic stroke but has limited validation. Cerebral blood volume (CBV) has been proposed as the best predictor of infarct core. We tested CBV against other common CTP parameters using contemporaneous diffusion MRI. METHODS: Patients with acute ischemic stroke<6 hours after onset had CTP and diffusion MRI<1 hour apart, before any reperfusion therapies. CTP maps of time to peak (TTP), absolute and relative CBV, cerebral blood flow (CBF), mean transit time (MTT), and time to peak of the deconvolved tissue residue function (Tmax) were generated. The diffusion lesion was manually outlined to its maximal visual extent. Receiver operating characteristic (ROC) analysis area under the curve (AUC) was used to quantify the correspondence of each perfusion parameter to the coregistered diffusion-weighted imaging lesion. Optimal thresholds were determined (Youden index). RESULTS: In analysis of 98 CTP slabs (54 patients, median onset to CT 190 minutes, median CT to MR 30 minutes), relative CBF performed best (AUC, 0.79; 95% CI, 0.77-81), significantly better than absolute CBV (AUC, 0.74; 95% CI, 0.73-0.76). The optimal threshold was <31% of mean contralateral CBF. Specificity was reduced by low CBF/CBV in noninfarcted white matter in cases with reduced contrast bolus intensity and leukoaraiosis. CONCLUSIONS: In contrast to previous reports, CBF corresponded with the acute diffusion-weighted imaging lesion better than CBV, although no single threshold avoids detection of false-positive regions in unaffected white matter. This relates to low signal-to-noise ratio in CTP maps and emphasizes the need for optimized acquisition and postprocessing. PMID- 21980203 TI - Aspirin as a promising agent for decreasing incidence of cerebral aneurysm rupture. PMID- 21980204 TI - Thrombolytic therapy rates and stroke severity: an analysis of data from the Swedish stroke register (Riks-Stroke) 2007-2010. AB - BACKGROUND AND PURPOSE: We tested the hypothesis that higher proportions of patients with minor stroke being treated with thrombolysis contribute to increasing overall rates of thrombolysis. METHODS: We included 1743 ischemic stroke patients (age 18-80 years) treated with thrombolysis, recorded in the Swedish stroke register Riks-Stroke between 2007 and 2010. Minor stroke was defined as National Institutes of Health Stroke Scale score <= 5. RESULTS: The proportion with minor stroke among patients treated with thrombolysis increased from 22.1% in 2007 to 28.7% in 2010 (P=0.021). The rate of increase did not differ significantly between men and women, age groups, or hospital types (university hospitals, other large hospitals, or community hospitals). Hospitals with high proportions of thrombolysis patients with minor stroke were more likely to have high thrombolysis frequencies (R=0.55; P<0.001). CONCLUSIONS: In recent years, an increase in the proportion of patients with minor stroke treated with thrombolysis has contributed to rising overall thrombolysis rates in Sweden. At the hospital level, high rates of thrombolysis are associated with a high proportion of minor stroke being treated. PMID- 21980205 TI - Age and outcomes after carotid stenting and endarterectomy: the carotid revascularization endarterectomy versus stenting trial. AB - BACKGROUND AND PURPOSE: High stroke event rates among carotid artery stenting (CAS)-treated patients in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) lead-in registry generated an a priori hypothesis that age may modify the relative efficacy of CAS versus carotid endarterectomy (CEA). In the primary CREST report, we previously noted significant effect modification by age. Here we extend this investigation by examining the relative efficacy of the components of the primary end point, the treatment-specific impact of age, and contributors to the increasing risk in CAS-treated patients at older ages. METHODS: Among 2502 CREST patients with high-grade carotid stenosis, proportional hazards models were used to examine the impact of age on the CAS-to-CEA relative efficacy, and the impact of age on risk within CAS-treated and CEA-treated patients. RESULTS: Age acted as a treatment effect modifier for the primary end point (P interaction=0.02), with the efficacy of CAS and CEA approximately equal at age 70 years. For CAS, risk for the primary end point increased with age (P<0.0001) by 1.77-times (95% confidence interval, 1.38-2.28) per 10-year increment; however, there was no evidence of increased risk for CEA-treated patients (P=0.27). Stroke events were the primary contributor to the overall effect modification (P interaction=0.033), with equal risk at ~64 years. The treatment-by-age interaction for CAS and CEA was not altered by symptomatic status (P=0.96) or by sex (P=0.45). CONCLUSIONS: Outcomes after CAS versus CEA were related to patient age, attributable to increasing risk for stroke after CAS at older ages. Patient age should be an important consideration when choosing between the 2 procedures for treating carotid stenosis. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004732. PMID- 21980206 TI - Risk profile of intracranial aneurysms: rupture rate is not constant after formation. AB - BACKGROUND AND PURPOSE: Management of asymptomatic unruptured intracranial aneurysms remains controversial, and recent prospective follow-up studies showed that the rupture rate of small aneurysms is very low. These results are inconsistent with the finding that the majority of ruptured aneurysms in patients with subarachnoid hemorrhage are small. METHODS: A Markov model was constructed to simulate the natural history of intracranial aneurysms. All epidemiological and statistical data obtained from the Portal Site of Official Statistics of Japan (e-Stat) were adjusted to the standardized age distribution. From the selected data of aneurysm formation, the prevalence of unruptured aneurysms was estimated as 1.45% and the incidence of subarachnoid hemorrhage calculated to be 19.7/100 000/year in the whole standardized population. RESULTS: The function for rupture rate constant with time was first analyzed. Selected values for annual rupture rates of 0.3%, 0.5%, 0.7%, and 1.0% showed inconsistencies in the relationship between the prevalence of unruptured aneurysm and the incidence of subarachnoid hemorrhage. Next, the function for a short period of high risk followed by a long period of low risk was considered. Annual rupture rates of 0.5%, 0.7%, and 1.0% indicated epidemiological compatibility with additional early rupture rates of 20%, 15%, and 10%, respectively. CONCLUSIONS: This study suggests that some aneurysms bleed shortly after formation and thus are rarely detected as unruptured aneurysms. Most aneurysms without early rupture remain stable for the remainder of life through some healing process, and prophylactic treatment for incidentally identified small unruptured aneurysms has no rationale. PMID- 21980207 TI - Contrast extravasation on computed tomography angiography predicts clinical outcome in primary intracerebral hemorrhage: a prospective study of 139 cases. AB - BACKGROUND AND PURPOSE: Several retrospective studies suggested that contrast extravasation on CT angiography predicts hematoma expansion, poor outcome, and mortality in primary intracerebral hemorrhage. We aimed to determine the predictive value of contrast extravasation on multidetector CT angiography for clinical outcome in a prospective study. METHODS: In 160 consecutive patients with spontaneous intracerebral hemorrhage admitted within 6 hours of symptom onset, noncontrast CT and multidetector CT angiography were performed on admission. A follow-up noncontrast CT was done at 24 hours. Multidetector CT angiography images were analyzed to identify the presence of contrast extravasation. Clinical outcome was assessed by modified Rankin Scale on discharge and at 90 days. RESULTS: A total of 139 patients with primary intracerebral hemorrhage were included in the final analysis. Contrast extravasation occurred in 30 (21.6%) patients. The presence of contrast extravasation was associated with increased hematoma expansion (P<0.0001), in hospital mortality (P=0.008), prolonged hospital stay (P=0.006), poor outcome on discharge (P=0.025), increased 3-month mortality (P=0.009), and poor clinical outcome (P<0.0001). In multivariate analysis, contrast extravasation was a promising independent predictor (OR, 10.5; 95% CI, 3.2-34.7; P<0.0001) for 90-day poor clinical outcome followed by the presence of intraventricular hemorrhage (OR, 3.4; 95% CI, 1.5-7.7; P=0.003) and initial hematoma volume (OR, 1.0; 95% CI, 1.0-1.1; P=0.013). CONCLUSIONS: The presence of contrast extravasation on multidetector CT angiography in patients with hyperacute-stage intracerebral hemorrhage is an independent and strong factor associated with poor outcome. Any patient with intracerebral hemorrhage with such sign on multidetector CT angiography should be monitored intensely and treated accordingly. PMID- 21980208 TI - Aspirin as a promising agent for decreasing incidence of cerebral aneurysm rupture. AB - BACKGROUND AND PURPOSE: Chronic inflammation is postulated as an important phenomenon in intracranial aneurysm wall pathophysiology. This study was conducted to determine if aspirin use impacts the occurrence of intracranial aneurysm rupture. METHODS: Subjects enrolled in the International Study of Unruptured Intracranial Aneurysms (ISUIA) were selected from the prospective untreated cohort (n=1691) in a nested case-control study. Cases were subjects who subsequently had a proven aneurysmal subarachnoid hemorrhage during a 5-year follow-up period. Four control subjects were matched to each case by site and size of aneurysm (58 cases, 213 control subjects). Frequency of aspirin use was determined at baseline interview. Aspirin frequency groups were analyzed for risk of aneurysmal hemorrhage. Bivariable and multivariable analyses were performed using conditional logistic regression. RESULTS: A trend of a protective effect for risk of unruptured intracranial aneurysm rupture was observed. Patients who used aspirin 3* weekly to daily had an OR for hemorrhage of 0.40 (95% CI, 0.18 0.87); reference group, no use of aspirin), patients in the "< once a month" group had an OR of 0.80 (95% CI, 0.31-2.05), and patients in the "> once a month to 2*/week" group had an OR of 0.87 (95% CI, 0.27-2.81; P=0.025). In multivariable risk factor analyses, patients who used aspirin 3 times weekly to daily had a significantly lower odds of hemorrhage (adjusted OR, 0.27; 95% CI, 0.11-0.67; P=0.03) compared with those who never take aspirin. CONCLUSIONS: Frequent aspirin use may confer a protective effect for risk of intracranial aneurysm rupture. Future investigation in animal models and clinical studies is needed. PMID- 21980209 TI - The hyperintense acute reperfusion marker on fluid-attenuated inversion recovery magnetic resonance imaging is caused by gadolinium in the cerebrospinal fluid. AB - BACKGROUND AND PURPOSE: The hyperintense acute reperfusion marker (HARM) on fluid attenuated inversion recovery MRI is believed to be caused by gadolinium-based contrast agents crossing a disrupted blood-brain barrier. However, this hypothesis has never been directly verified in humans. METHODS: In this study, we analyzed cerebrospinal fluid samples of patients with HARM on imaging regarding the presence and concentration of gadolinium-based contrast agents. RESULTS: Gadobutrol was found in concentrations of approximately 50 MUmol/L. Using phantom MRI experiments, we demonstrate that the detected concentrations are consistent with the observed HARM imaging pattern. CONCLUSIONS: Our study yields first direct evidence in humans that the imaging phenomenon HARM is indeed caused by leakage of gadolinium-based contrast agents into the cerebrospinal fluid. PMID- 21980210 TI - Hospitalization costs for patients with acute ischemic stroke treated with endovascular embolectomy in the United States. AB - BACKGROUND AND PURPOSE: It is important to know the costs of hospitalization for patients undergoing endovascular embolectomy so that comparisons can be made with payments to hospitals. METHODS: Using the National Inpatient Sample, we evaluated the costs of hospitalization for patients treated with endovascular embolectomy in the United States from 2006 to 2008. The primary end point examined in this study was total hospital costs, and these were correlated with clinical outcome. RESULTS: A total of 3864 patients received endovascular embolectomy. A total of 1649 patients were <65 years old and 2205 patients were >=65 years old. Median hospital costs in 2008 dollars were $36,999 (interquartile range, $26,662 $56,405) for patients with good outcome, $50,628 (interquartile range, $33,135 $76,063) for patients with severe disability, and $35,109 (interquartile range, $25,053-$62,621) for patients with mortality. CONCLUSIONS: Hospitalization costs for patients treated with endovascular embolectomy are rather high, probably due to the serious nature of their illness. Medicare payments have not been adequate reimbursement for these hospitalizations. PMID- 21980211 TI - Blood pressure reduction, decreased diffusion on MRI, and outcomes after intracerebral hemorrhage. AB - BACKGROUND AND PURPOSE: Decreased diffusion (DD) consistent with acute ischemia may be detected on MRI after acute intracerebral hemorrhage (ICH), but its risk factors and impact on functional outcomes are not well-defined. We tested the hypotheses that DD after ICH is related to acute blood pressure (BP) reduction and lower hemoglobin and presages worse functional outcomes. METHODS: Patients who underwent MRI were prospectively evaluated for DD by certified neuroradiologists blinded to outcomes. Hemoglobin and BP data were obtained via electronic queries. Outcomes were obtained at 14 days and 3 months with the modified Rankin Scale, a functional scale scored from 0 (no symptoms) to 6 (dead). We used logistic regression for dependence or death (modified Rankin Scale score 4-6). RESULTS: DD distinct from the hematoma was found on MRI in 39 of 95 patients (41%). DD was associated with greater BP reductions from baseline and a higher risk of dependence or death at 3 months (odds ratio, 4.8; 95% confidence interval, 1.7-13.9; P=0.004) after correction for ICH score (1.8 per point; 95% confidence interval, 1.2-3.1; P=0.01). Lower hemoglobin was associated with worse ICH score, larger hematoma volume, and worse outcomes, but not DD. CONCLUSIONS: DD is common after ICH, associated with greater acute BP reductions, and associated with disability and death at 3 months in multivariate analysis. The potential benefits of acute BP reduction to reduce hematoma growth may be limited by DD. The prevention and treatment of cerebral ischemia manifested as DD are potential methods to improve outcomes. PMID- 21980212 TI - Angiogenic T-cells and putative endothelial progenitor cells in hypertension related cerebral small vessel disease. AB - BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) may be caused by endothelial dysfunction, whereas endothelial progenitor cells (EPC) may attenuate endothelial dysfunction. Their vitality is lower in CSVD. A subset of lymphocytes, angiogenic T-cells, is capable to stimulate EPC function. The purpose of our study was to explore the relation between CSVD manifestations, angiogenic T-cells, and EPC in hypertensive patients with CSVD. METHODS: We compared 32 essential hypertensive patients with CSVD (white matter lesions, asymptomatic lacunar infarcts, or microbleeds on 1.5-Tesla MRI) to 29 age-matched and sex-matched hypertensive controls. We counted angiogenic T-cells (CD3(+)/CD31(+)/CD184(+)) and putative EPC (CD31(+)/CD34(+)/CD45(-)/KDR(+)) by flow cytometry and determined EPC vitality by in vitro cluster formation. RESULTS: Putative EPC numbers were lower in hypertensive individuals with CSVD than in those without (10+/-7(.)10(3)/mL versus 13+/-6(.)10(3)/mL [median+/ interquartile range]; P=0.011). Angiogenic T-cell numbers were also lower in hypertensive individuals with CSVD than in those without (0.56+/-0.25(.)10(9)/mL versus 0.78+/-0.50(.)10(9)/mL; P=0.008). Higher angiogenic T-cell numbers independently related to absence of CSVD (odds ratio, 0.088; 95% confidence interval, 0.012-0.627). CONCLUSIONS: Our data suggest that angiogenic T-cells and putative EPC independently relate to radiological CSVD manifestations in hypertensive patients. PMID- 21980213 TI - Stroke quality metrics: systematic reviews of the relationships to patient centered outcomes and impact of public reporting. AB - BACKGROUND AND PURPOSE: Stroke quality metrics play an increasingly important role in quality improvement and policies related to provider reimbursement, accreditation, and public reporting. We conducted 2 systematic reviews examining the relationships between compliance with stroke quality metrics and patient centered outcomes, and public reporting of stroke metrics and quality improvement, quality of care, or outcomes. METHODS: MEDLINE and EMBASE databases were searched to identify studies that evaluated the relationship between stroke quality metric compliance and patient-centered outcomes in acute hospital settings and public reporting of stroke quality metrics and quality improvement activities, quality of care, or patient outcomes. We specifically excluded studies that evaluated the effect of stroke units or hospital certification. RESULTS: Fourteen studies met eligibility criteria for the review of stroke quality metric compliance and patient-centered outcomes; 9 found mostly positive associations, whereas 5 found no or very limited associations. Only 2 eligible studies were found that directly addressed the public reporting of stroke quality metrics. CONCLUSIONS: Some studies have found positive associations between stroke metric compliance and improved patient-centered outcomes. However, high quality studies are lacking and several methodological difficulties make the interpretation of the reported associations challenging. Information on the impact of public reporting of stroke quality metric data is extremely limited. Legitimate questions remain as to whether public reporting of stroke metrics is accurate, effective, or has the potential for unintended consequences. The generation of high-quality data examining quality metrics and stroke outcomes as well as the impact of public reporting should be given priority. PMID- 21980214 TI - Neurosurgical advances in the treatment of moyamoya disease. AB - BACKGROUND AND PURPOSE: Moyamoya disease is characterized by chronic stenoocclusive vasculopathy involving the distal supraclinoid internal carotid arteries and presents with ischemic or hemorrhagic symptoms. We review advances in the understanding and management of moyamoya disease. SUMMARY OF REVIEW: Cerebral revascularization, either direct or indirect, is the cornerstone of treatment for moyamoya disease. Recent advances have been made in understanding the molecular biology and pathophysiology of moyamoya disease, and new genetic mutations and deletions have been identified. Imaging for moyamoya disease is also rapidly improving with new sequences of MRI and better methods of assessing ischemia and cerebrovascular reserve. Positron emission tomography has emerged as an important tool to measure cerebrovascular reserve. Novel surgical techniques assess patency and ischemia during superficial temporal to middle cerebral artery bypass, including indocyanine green videoangiography to evaluate anastomosis patency, and various methods to monitor intraoperative blood flow. Newer methods of indirect revascularization have been described with placement of more tissues supplied by the external carotid artery on the brain surface. Postoperative hyperperfusion to the chronically ischemic brain tissue is a recently identified causative factor of complications. Interestingly, complications from hyperperfusion mimic those caused by ischemia, although they have different treatments, making the role of postoperative blood flow assessment important in distinguishing between the two. Awareness has also increased that even asymptomatic patients can experience significant cognitive decline attributable to chronic ischemia. Whether this reverts after successful revascularization requires investigation. CONCLUSIONS: Surgical revascularization with direct, indirect, and combined methods remains the preferred procedure for patients with moyamoya disease. PMID- 21980215 TI - Sobre as inclinacoes carnais: inflexoes do pensamento cristao sobre os desejos e as sensacoes prazerosas do baixo corporal. AB - This study develops a historical review of the meanings of the "flesh" in the West, focusing on its significance in the context of Christianity. Our hope is that a study along these lines can help to illuminate current understandings of questions related to sexuality both within and outside of the religious contexts found in contemporary Brazil. Such questions are of special interest for those who are concerned with both old and new problems found in the field that has come to be known as sexual and reproductive rights, with implications for the field of Public Health. PMID- 21980216 TI - National Income and Income Inequality, Family Affluence and Life Satisfaction Among 13 year Old Boys and Girls: A Multilevel Study in 35 Countries. AB - Adolescence is a critical period where many patterns of health and health behaviour are formed. The objective of this study was to investigate cross national variation in the relationship between family affluence and adolescent life satisfaction, and the impact of national income and income inequality on this relationship. Data from the 2006 Health Behaviour in School-aged Children: WHO collaborative Study (N = 58,352 across 35 countries) were analysed using multilevel linear and logistic regression analyses for outcome measures life satisfaction score and binary high/low life satisfaction. National income and income inequality were associated with aggregated life satisfaction score and prevalence of high life satisfaction. Within-country socioeconomic inequalities in life satisfaction existed even after adjustment for family structure. This relationship was curvilinear and varied cross-nationally. Socioeconomic inequalities were greatest in poor countries and in countries with unequal income distribution. GDP (PPP US$) and Gini did not explain between country variance in socioeconomic inequalities in life satisfaction. The existence of, and variation in, within-country socioeconomic inequalities in adolescent life satisfaction highlights the importance of identifying and addressing mediating factors during this life stage. PMID- 21980217 TI - College Education and Social Trust: An Evidence-Based Study on the Causal Mechanisms. AB - This paper examines the influence of college education on social trust at the individual level. Based on the literature of trust and social trust, we hypothesize that life experience/development since adulthood and perceptions of cultural/social structures are two primary channels in the causal linkage between college education and social trust. In the first part of the empirical study econometric techniques are employed to tackle the omitted-variable problem and substantial evidence is found to confirm the positive effect of college education. In the second part contemporary information is used to examine the hypothetical mechanisms in the causal inference. That life experience is a primary channel via which college education promotes social trust fails to find support in our examination, while individual perceptions of cultural and social structures explain up to 77% of the causal effect. PMID- 21980218 TI - Income and Happiness in Time of Post-Communist Modernization. AB - This paper discusses the relations between economic development, family income, and happiness in post-communist Poland from the point of view of Inglehart's theory of modernization. The happiness is understood as satisfaction with income and life, and as psychological well-being. The analysis of survey data yields the conclusion that economic development reduces the strength of the relations between income and satisfaction as well as between income and psychological well being. These findings may be explained by changes in the value system from collectivist/materialist to individualist/post-materialist, even when these values are not directly measured. The analyzed data are from a series of representative surveys conducted in Poland during a period of political and economic transformation (i.e., between 1989 and 2008). Official statistical data on Polish economic development during the same period are used as a background for survey results. The relations between income and happiness change in Poland in a way consistent with Inglehart's modernization theory. PMID- 21980219 TI - Algebraic construction of a Nambu bracket for the two-dimensional vorticity equation. AB - So far fluid mechanical Nambu brackets have mainly been given on an intuitive basis. Alternatively an algorithmic construction of such a bracket for the two dimensional vorticity equation is presented here. Starting from the Lie-Poisson form and its algebraic properties it is shown how the Nambu representation can be explicitly constructed as the continuum limit from the structure preserving Zeitlin discretization. PMID- 21980220 TI - Introduction to serial reviews: physiological relevance of antioxid/redox genes; learning from genetically modified animals. PMID- 21980221 TI - Unveiling the roles of the glutathione redox system in vivo by analyzing genetically modified mice. AB - Redox status affects various cellular activities, such as proliferation, differentiation, and death. Recent studies suggest pivotal roles of reactive oxygen species not only in pathogenesis under oxidative insult but also in intracellular signal transduction. Glutathione is present in several millimolar concentrations in the cytoplasm and has multiple roles in the regulation of cellular homeostasis. Two enzymes, gamma-glutamylcysteine synthetase and glutathione synthetase, constitute the de novo synthesis machinery, while glutathione reductase is involved in the recycling of oxidized glutathione. Multidrug resistant proteins and some other transporters are responsible for exporting oxidized glutathione, glutathione conjugates, and S-nitrosoglutathione. In addition to antioxidation, glutathione is more positively involved in cellular activity via its sulfhydryl moiety of a molecule. Animals in which genes responsible for glutathione metabolism are genetically modified can be used as beneficial and reliable models to elucidate roles of glutathione in vivo. This review article overviews recent progress in works related to genetically modified rodents and advances in the elucidation of glutathione-mediated reactions. PMID- 21980222 TI - Direct assessment by electron spin resonance spectroscopy of the antioxidant effects of French maritime pine bark extract in the maxillofacial region of hairless mice. AB - Flavangenol, one of extract of French maritime pine bark, is a complex mixture of bioflavonoids with oligometric proanthocyanidins as the major constituents. These constituents, catechin and procyanidin B(1), are water-soluble derivatives of flavangenol. In this study, we investigated the antioxidant effects of flavangenol on reactive oxygen species such as hydroxyl radical, superoxide anion and singlet oxygen using electron spin resonance and spin trapping. The effect of flavangenol on oxidative stress in the skin from the maxillofacial region of hairless mice was investigated using an in vivo L-band electron spin resonance imaging system. Flavangenol attenuated oxidative stress in the maxillofacial skin by acting as a reactive oxygen species scavenger, as demonstrated by in vitro and in vivo electron spin resonance imaging analysis. The absorption and metabolism of flavangenol were also examined. After oral administration of flavangenol in human and rat, most of the catechin in plasma was in the conjugated form, while 45% to 78% of procyanidin B(1) was unconjugated, indicating that non-conjugated procyanidin B(1) would be active in the circulation. The ability of flavangenol to reduce reactive oxygen species levels in the circulation of the maxillofacial region suggests that this extract may be beneficial for skin protection from exposure to ultraviolet irradiation. PMID- 21980223 TI - Reevaluation of analytical methods for photogenerated singlet oxygen. AB - The aim of the present study is to compare different analytical methods for singlet oxygen and to discuss an appropriate way to evaluate the yield of singlet oxygen photogenerated from photosensitizers. Singlet oxygen photogenerated from rose bengal was evaluated by electron spin resonance analysis using sterically hindered amines, spectrophotometric analysis of 1,3-diphenylisobenzofuran oxidation, and analysis of fluorescent probe (Singlet Oxygen Sensor Green(r)). All of the analytical methods could evaluate the relative yield of singlet oxygen. The sensitivity of the analytical methods was 1,3-diphenylisobenzofuran < electron spin resonance < Singlet Oxygen Sensor Green(r). However, Singlet Oxygen Sensor Green(r) could be used only when the concentration of rose bengal was very low (<1 uM). In addition, since the absorption spectra of 1,3 diphenylisobenzofuran is considerably changed by irradiation of 405 nm laser, photosensitizers which are excited by light with a wavelength of around 400 nm such as hematoporphyrin cannot be used in the 1,3-diphenylisobenzofuran oxidation method. On the other hand, electron spin resonance analysis using a sterically hindered amine, especially 2,2,6,6-tetramethyl-4-piperidinol and 2,2,5,5 tetramethyl-3-pyrroline-3-carboxamide, had proper sensitivity and wide detectable range for the yield of photogenerated singlet oxygen. Therefore, in photodynamic therapy, it is suggested that the relative yield of singlet oxygen generated by various photosensitizers can be evaluated properly by electron spin resonance analysis. PMID- 21980224 TI - Free radical formation from sonolysis of water in the presence of different gases. AB - In the present study by applying electron spin resonance-spin trapping method, when a high frequency (1650 kHz) ultrasound was irradiated to water dissolved with different gas molecules (O(2), N(2), Ar, Ne, He, and H(2)) at 25 degrees C of water bulk temperature, free radical generation pattern differed dependently on the dissolved gas molecules. Only (*)OH was detected in the O(2)-dissolved water sample, and the amount of the radical was much greater than that determined in any of other gas-dissolved water samples. One of the possible reasons to explain why the (*)H radical was not detected in the O(2)-dissolved water is that the (*)H reacts with O(2) to form (*)OOH. However, no electron spin resonance signals related to the adduct of not only 5,5-dimethyl-1-pyrroline-N-oxide but 5 (2,2-Dimethyl-1,3-propoxy cyclophosphoryl)-5-methyl-1-pyrroline N-oxide and (*)OOH were observed. In the H(2)-dissolved water, only (*)H was detected, suggesting that H(2) reduces or neutralizes (*)OH. In the N(2)-disolved water, both (*)OH and (*)H were detected at comparable level. In the water samples dissolved with rare gases (Ar, Ne, and He), the amount of (*)H was almost double as compared with that of (*)OH, and both (*)OH and (*)H yields increased in the order Ar > Ne > He. PMID- 21980225 TI - Effects of the interaction of diabetes and iron supplementation on hepatic and pancreatic tissues, oxidative stress markers, and liver peroxisome proliferator activated receptor-alpha expression. AB - This study evaluated the effects of the interaction of diabetes and a carbonyl iron supplemented on hepatic and pancreatic tissues, oxidative stress markers and liver peroxisome proliferator-activated receptor-alpha expressions. Hamsters were divided: Control which received a standard AIN 93 diet; Control Iron, composed of control animals that received a diet with 0.83% carbonyl iron; Diabetic, composed of animals that received a injection of streptozotocin (50 mg/kg, intraperitoneal) on day 35; and Diabetic Iron composed of streptozotocin treated animals that received a diet supplemented with carbonyl iron. Diabetes increased the glucose level and reduced triglycerides. Diabetic Iron group showed higher levels of glucose and serum triglycerides as compared to the Diabetic group. Diabetes decreased mRNA levels of peroxisome proliferator-activated receptor alpha. Iron attenuated the diabetes induced down regulation of peroxisome proliferator-activated receptor-alpha mRNA. Moreover, diabetes increased carbonyl protein and decreased glutathione levels and catalase activity, while iron attenuated the increase in levels of carbonyl protein and attenuated the decrease in those of glutathione level and catalase activity. Histological analysis shows that supplementation iron caused an increase in the size of the islets in Control Iron. The results show that iron does not aggravated liver oxidant/antioxidant status and peroxisome proliferator-activated receptor-alpha expression in diabetic hamsters. PMID- 21980226 TI - High phosphate diet reduces atherosclerosis formation in apolipoprotein E deficient mice. AB - Although higher serum phosphate level is a risk factor for cardiovascular diseases in general population as well as chronic kidney disease patients, it has not been clarified whether higher phosphate can affect atherosclerotic plaque formation. In this study, we investigated the effect of prolonged-intake of different concentrations of phosphate on atherosclerosis formation using apolipoprotein E-deficient mice. Apolipoprotein E-deficient mice were fed with high fat diet including 0.6%, 1.2% or 1.8% phosphate. After 20-week treatment, atherosclerotic plaque formation in aorta in 1.8% phosphate diet group was unexpectedly less than that in the other groups. To elucidate mechanisms of suppression of plaque formation by high phosphate diet, we hypothesized that high phosphate diet may modify a profile of monocytes/macrophages suppressing plaque formation. We confirmed that elevated peripheral monocytes (CD11b+, F4/80+ cell numbers) in apolipoprotein E-deficient mice were decreased by feeding with 1.8% P diet. In addition, ex vivo study indicated that high dose of phosphate induced macrophage apoptosis. These observations suggest that excess phosphate intake decreased atherosclerosis formation, at least in part, by changing the profile of peripheral monocytes or inducing apoptosis of macrophages in apolipoprotein E deficient mice. PMID- 21980227 TI - Determining amino acid requirements from repeated observations on indicator amino acid oxidation method by mixed-effect change-point regression models. AB - In nutrition studies, it is often of primary interest to determine the critical threshold value of some biological quantities. To determine the amino acid requirement, the tracer approach including the indicator amino acid oxidation method is useful for the investigation of human subjects. In this approach, measurements of amino acids other than the test amino acid are often repeatedly carried out with various intakes of the test amino acid. Change-point regression models have often been applied to determine the amino acid requirement. However, within-subject dependence due to repeated measurements has not been sufficiently taken into account. In this paper, we propose a mixed-effect change-point model to estimate the amino acid requirements when utilizing the tracer approach. Inference based on Akaike Information Criteria is introduced to include selection of the optimal model and construction of a confidence interval. Our method can easily be applied with a standard software package, and we found that appropriate accounting for within-subject dependence may lead to a much narrower confidence interval. We recommend application of a mixed-effect change-point regression model to determine the amino acid requirements in studies utilizing the tracer approach. PMID- 21980228 TI - Age- and sun exposure-dependent differences in 8-hydroxy-2'-deoxyguanosine and N (carboxymethyl)lysine in human epidermis. AB - Aging and exposure to sunlight are two major factors in the deterioration of skin function. In this study, thirty-six fixed human skin samples from sun-exposed and unexposed areas from young and old individuals were used to evaluate the localization of oxidative stress according to levels and distribution of 8 hydroxy-2'-deoxyguanosine and N(epsilon)-(carboxymethyl)lysine in samples using immunohistochemistry. In the epidermis of the young, negligible amounts of 8 hydroxy-2'-deoxyguanosine and N(epsilon)-(carboxymethyl)lysine were detected in unexposed areas, whereas nuclear 8-hydroxy-2'-deoxyguanosine and cytoplasmic N(epsilon)-(carboxymethyl)lysine were increased in the lower epidermis in sun exposed areas. In contrast, the aged presented prominent nuclear 8-hydroxy-2' deoxyguanosine and nuclear N(epsilon)-(carboxymethyl)lysine in the epidermis of unexposed areas, concomitant with dermal increase in N(epsilon) (carboxymethyl)lysine. However, the immunostaining of 8-hydroxy-2'-deoxyguanosine and N(epsilon)-(carboxymethyl)lysine revealed a decrease in the epidermis of sun exposed areas in the aged. These results suggest an age-dependent difference in the adaptation and protective mechanisms of the epidermis against sunlight associated oxidative stress, thus necessitating distinct standards for evaluation in each age group. Further investigation is warranted to elucidate underlying molecular mechanisms. PMID- 21980229 TI - In-air microparticle induced X-ray emission analysis of particles in interstitial pneumonia lung tissue obtained by transbronchial biopsy. AB - Interstitial pneumonia develops in association with inhaled particles. In-air microparticle induced X-ray emission (in-air micro) analysis was previously employed to assess the spatial distribution and content of particles in surgical lung biopsy specimens. The aim of this study was to assess the efficacy of in-air micro-analysis for transbronchial lung biopsy specimens in patients with or without occupational exposure. The elements composing lung particles and their locations could be identified by in-air micro-analysis. Silicon was the major component of particles. Quantitative analysis revealed that the elements composing lung particles varied between patients. In a patient with suspected nickel exposure, aluminium, vanadium, and calcium were detected, but was not detected. In a patient without a work history (housewife), various elements were detected. In-air micro-analysis was useful for assessing the spatial distribution and content of particles in specimens from patients. Occupational exposure was not necessarily associated with deposition of particles in the lungs. Therefore, in the diagnosis of, elemental analysis of specimens by in-air micro-analysis could be useful for assessing exposure to particles objectively. PMID- 21980230 TI - Relationship between the estimates of desaturase activities and cardiometabolic phenotypes in Koreans. AB - In the present study, we evaluated the relationships of estimated desaturase activities with cardiometabolic risk factors including abdominal obesity, atherogenic lipoprotein phenotype and inflammation in Koreans. Ninety-three healthy volunteers participated in this cross-sectional study. LDL particle size was determined using gradient gel electrophoresis and inflammatory markers including C-reactive protein, soluble intercellular adhesion molecule-1, and adiponectin were measured. Stearoyl-coA desaturase, delta-6 desaturase and delta 5 desaturase were estimated as precursor to fatty acid ratios. The results showed that stearoyl-coA desaturase was correlated with body mass index (r = 0.235, p<0.05), triglyceride (r = 0.261, p<0.001), and HDL-cholesterol (r = -0.226, p<0.05). Stearoyl-coA desaturase was associated with only triglyceride (r = 0.283, p<0.01). Delta-6 desaturase was correlated with body mass index (r = 0.236, p<0.05), waist circumference (r = 0.218, p<0.05), triglyceride (r = 0.399, p<0.001), C-reactive protein (r = 0.333, p<0.001), soluble intercellular adhesion molecule-1 (r = 0.229, p<0.05), HDL-cholesterol (r = -0.325, p<0.01), LDL particle size (r = -0.297, p<0.01) and adiponectin (r = -0.233, p<0.05). In contrast, delta-5 desaturase was correlated with body mass index (r = -0.324, p<0.01), waist circumference (r = -0.276, p<0.01), triglyceride (r = -0.329, p<0.01), C-reactive protein (r = -0.215, p<0.05), HDL-cholesterol (r = 0.262, p<0.05) and LDL particle size (r = 0.278, p<0.01). Stepwise multiple regression analysis revealed that delta-6 desaturase (p<0.01) together with waist circumference (p<0.001) were found to be independent factors for determining plasma levels of C-reactive protein (R(2) = 0.230). Estimated desaturase activities are closely associated with the features of cardiometabolic risk in Koreans. PMID- 21980231 TI - The role of trefoil factor family in apparently healthy subjects administrated gastroprotective agents for the primary prevention of gastrointestinal injuries from low-dose acetylsalicylic acid: a preliminary study. AB - It is well-known that acetylsalicylic acid induces gastrointestinal complication. Recently, trefoil factor family has been reported as a mucosal protective factor. We focused on trefoil factor family as one of defensive system for gastrointestinal injuries. The aim of this trial was to evaluate trefoil factor family levels in the serum of healthy subjects with low-dose acetylsalicylic acid. Low-dose acetylsalicylic acid with placebo or proton pump inhibitor or rebamipide were administered in 30 healthy subjects. Transnasal endoscopy was performed at 0, 24 h, 3 and 7 day. Changing of trefoil factor family (1,2,3) and numbers of gastric injuries were evaluated. The numbers of gastric injuries were significantly increased in the placebo group at 3 and 7 days. Injuries in the proton pump inhibitor group were not induced, in the rebamipide group were slightly induced. Trefoil factor family level in the placebo group were decreased in 3 and 7 days compared with prior to starting the trial. Trefoil factor family may have an important association with acetylsalicylic acid-induced gastrointestinal damage. Proton pump inhibitor and rebamipide prevented low-dose acetylsalicylic acid-induced gastrointestinal complications compared with the placebo group. PMID- 21980232 TI - Formation of 7-carboxyheptyl radical induced by singlet oxygen in the reaction mixture of oleic acid, riboflavin and ferrous ion under the UVA irradiation. AB - Identification of the radicals was performed for the standard reaction mixtures, which contained 4.3 mM oleic acid, 25 uM riboflavin, 1 mM FeSO(4)(NH(4))(2)SO(4), 10 mM cholic acid, 40 mM phosphate buffer (pH 7.4) and 0.1 M alpha-(4-pyridyl-1 oxide)-N-tert-butylnitrone under the UVA irradiation (365 nm), using an electron spin resonance, an high performance liquid chromatography-electron spin resonance and an high performance liquid chromatography-electron spin resonance-mass spectrometry. The electron spin resonance and high performance liquid chromatography-electron spin resonance measurements of the standard reaction mixtures showed prominent signals (alpha(N) = 1.58 mT and alpha(H)beta = 0.26 mT) and peaks 1 and 3 (retention times, 37.0 min and 49.0 min). Since the peak 3 was not observed for the standard reaction mixture without oleic acid, the radical of the peak 3 seems to be derived from oleic acid. Singlet oxygens seem to participate in the formation of the oleic acid-derived radicals because the peak height of the peak 3 observed in the standard reaction mixture of D(2)O increased to 308 +/- 72% of the control. The high performance liquid chromatography electron spin resonance-mass spectrometry analysis showed that 7-carboxyheptyl radical forms in the standard reaction mixture. PMID- 21980233 TI - Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA. AB - Nanoscaled devices have great potential for drug delivery applications due to their small size. In the present study, we report for the first time the preparation and evaluation of antitumor efficacy of 5-fluorouracil (5-FU) entrapped poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles with dependence on the lactide/glycolide combination of PLGA. 5-FU-loaded PLGA nanoparticles with two different monomer combinations, 50-50 and 90-10 were synthesized using a modified double emulsion method, and their biological evaluation was done in glioma (U87MG) and breast adenocarcinoma (MCF7) cell lines. 5-FU-entrapped PLGA 50-50 nanoparticles showed smaller size with a high encapsulation efficiency of 66%, which was equivalent to that of PLGA 90-10 nanoparticles. Physicochemical characterization of nanoparticles using differential scanning calorimetry and X-ray diffraction suggested the presence of 5-FU in molecular dispersion form. In vitro release studies showed the prolonged and sustained release of 5-FU from nanoparticles with both the PLGA combinations, where PLGA 50-50 nanoparticles showed faster release. Nanoparticles with PLGA 50 50 combination exhibited better cytotoxicity than free drug in a dose- and time dependent manner against both the tumor cell lines. The enhanced efficiency of PLGA 50-50 nanoparticles to induce apoptosis was indicated by acridine orange/ethidium bromide staining. Cell cycle perturbations studied using flow cytometer showed better S-phase arrest by nanoparticles in comparison with free 5 FU. All the results indicate that PLGA 50-50 nanoparticles possess better antitumor efficacy than PLGA 90-10 nanoparticles and free 5-FU. Since, studies have shown that long-term exposure of ailing tissues to moderate drug concentrations is more favorable than regular administration of higher concentration of the drug; our results clearly indicate the potential of 5-FU loaded PLGA nanoparticles with dependence on carrier combination as controlled release formulation to multiplex the therapeutic effect of cancer chemotherapy. PMID- 21980234 TI - Preliminary biocompatibility investigation of magnetic albumin nanosphere designed as a potential versatile drug delivery system. AB - BACKGROUND: The magnetic albumin nanosphere (MAN), encapsulating maghemite nanoparticles, was designed as a magnetic drug delivery system (MDDS) able to perform a variety of biomedical applications. It is noteworthy that MAN was efficient in treating Ehrlich's tumors by the magnetohyperthermia procedure. METHODS AND MATERIALS: In this study, several nanotoxicity tests were systematically carried out in mice from 30 minutes until 30 days after MAN injection to investigate their biocompatibility status. Cytometry analysis, viability tests, micronucleus assay, and histological analysis were performed. RESULTS: Cytometry analysis and viability tests revealed MAN promotes only slight and temporary alterations in the frequency of both leukocyte populations and viable peritoneal cells, respectively. Micronucleus assay showed absolutely no genotoxicity or cytotoxicity effects and histological analysis showed no alterations or even nanoparticle clusters in several investigated organs but, interestingly, revealed the presence of MAN clusters in the central nervous system (CNS). CONCLUSION: The results showed that MAN has desirable in vivo biocompatibility, presenting potential for use as a MDDS, especially in CNS disease therapy. PMID- 21980235 TI - Chemical nature and structure of organic coating of quantum dots is crucial for their application in imaging diagnostics. AB - BACKGROUND: One of the most attractive properties of quantum dots is their potential to extend the opportunities for fluorescent and multimodal imaging in vivo. The aim of the present study was to clarify whether the composition and structure of organic coating of nanoparticles are crucial for their application in vivo. METHODS: We compared quantum dots coated with non-crosslinked amino functionalized polyamidoamine (PAMAM) dendrimers, quantum dots encapsulated in crosslinked carboxyl-functionalized PAMAM dendrimers, and silica-shelled amino functionalized quantum dots. A multimodal fluorescent and paramagnetic quantum dot probe was also developed and analyzed. The probes were applied intravenously in anesthetized animals for visualization of brain vasculature using two-photon excited fluorescent microscopy and visualization of tumors using fluorescent IVIS((r)) imaging (Caliper Life Sciences, Hopkinton, MA) and magnetic resonance imaging. RESULTS: Quantum dots coated with non-crosslinked dendrimers were cytotoxic. They induced side effects in vivo, including vasodilatation with a decrease in mean arterial blood pressure and heart rate. The quantum dots penetrated the vessels, which caused the quality of fluorescent imaging to deteriorate. Quantum dots encapsulated in crosslinked dendrimers had low cytotoxicity and were biocompatible. In concentrations <0.3 nmol quantum dots/kg bodyweight, these nanoparticles did not affect blood pressure and heart rate, and did not induce vasodilatation or vasoconstriction. PEGylation (PEG [polyethylene glycol]) was an indispensable step in development of a quantum dot probe for in vivo imaging, based on silica-shelled quantum dots. The non-PEGylated silica shelled quantum dots possessed low colloidal stability in high-salt physiological fluids, accompanied by rapid aggregation in vivo. The conjugation of silica shelled quantum dots with PEG1100 increased their stability and half-life in the circulation without significant enhancement of their size. In concentrations <2.5 nmol/kg bodyweight, these quantum dots did not affect the main physiological variables. It was possible to visualize capillaries, which makes this quantum dot probe appropriate for investigation of mediators of vasoconstriction, vasodilatation, and brain circulation in intact animals in vivo. The multimodal silica-shelled quantum dots allowed visualization of tumor tissue in an early stage of its development, using magnetic resonance imaging. CONCLUSION: THE PRESENT STUDY SHOWS THAT THE TYPE AND STRUCTURE OF ORGANIC/BIOORGANIC SHELLS OF QUANTUM DOTS DETERMINE THEIR BIOCOMPATIBILITY AND ARE CRUCIAL FOR THEIR APPLICATION IN IMAGING IN VIVO, DUE TO THE EFFECTS OF THE SHELL ON THE FOLLOWING PROPERTIES: colloidal stability, solubility in physiological fluids, influence of the basic physiological parameters, and cytotoxicity. PMID- 21980236 TI - In-vivo imaging of oral squamous cell carcinoma by EGFR monoclonal antibody conjugated near-infrared quantum dots in mice. AB - OBJECTIVES: The purpose of this study was to investigate in-vivo visible imaging of oral squamous cell carcinoma (OSCC) by targeting epidermal growth factor receptor (EGFR) with near-infrared quantum dots. MATERIALS AND METHODS: Quantum dots with an emission wavelength of 800 nm (QD800) were conjugated to monoclonal antibodies against EGFR, resulting in the probe designated as QD800-EGFR Ab. OSCC cell line (BcaCD885) expressing high levels of EGFR was transplanted subcutaneously into nude mice cheeks to develop an OSCC animal model. QD800-EGFR Ab containing 100 pmol equivalent of QD800 was intravenously injected into the animal model, and in-situ and in-vivo imaging of cheek squamous cell carcinoma was analyzed at 10 different time points. RESULTS AND CONCLUSION: In-vivo imaging and immunohistochemical examination of the tumors showed that intravenously injected QD800-EGFR Ab probe could bind EGFR expressed on BcaCD885 cells. Fluorescence signals of BcaCD885 cells labeled with QD800-EGFR Ab probe could be clearly detected, and these fluorescence signals lasted for 24 hours. The most complete tumor images with maximal signal-to-noise ratio were observed from 15 minutes to 6 hours after injection of the probe. To the best of the authors' knowledge, this is the first study that has obtained clear in-situ and in-vivo imaging of head and neck cancer by using QD800-EGFR Ab probe. The authors conclude that the combination of near-infrared quantum dots that are highly penetrating for tissues with EGFR monoclonal antibody has promising prospects in in-vivo imaging of OSCC and development of personalized surgical therapies. PMID- 21980237 TI - Second-generation aptamer-conjugated PSMA-targeted delivery system for prostate cancer therapy. AB - BACKGROUND: miR-15a and miR-16-1 have been identified as tumor suppressor genes in prostate cancer, but their safe and effective delivery to target cells is key to the successful use of this therapeutic strategy. RNA aptamer A10 has been used as a ligand, targeting prostate cancer cells that express prostate-specific membrane antigen (PSMA). Compared with A10, the binding of the second-generation RNA aptamer, A10-3.2, to PSMA is more efficient. METHODS: A10-3.2 was investigated as a PSMA-targeting ligand in the design of a polyamidoamine (PAMAM) based microRNA (miR-15a and miR-16-1) vector to prostate cancer cells. Using polyethyleneglycol (PEG) as a spacer, PAMAM was conjugated to aptamer (PAMAM-PEG APT) and used as a vehicle for miRNA target delivery. RESULTS: Luciferase assays of pGL-3 expression against PC3 (PSMA(-)) and LNCaP (PSMA(+)) cells demonstrated that the transfection efficiency of the synthesized DNA/PAMAM-PEG-APT complex was higher than that of the DNA/PAMAM-PEG complex. In addition, cell viability assays of LNCaP (PSMA(+)) cells showed that, with a N/P ratio of 15:1, the IC(50) value of miRNA/PAMAM-PEG-APT was approximately 4.7-fold lower than that of miRNA/PAMAM PEG. CONCLUSION: This PSMA-targeted system may prove useful in widening the therapeutic window and allow for selective killing of prostate cancer cells. PMID- 21980238 TI - Multi-access drug delivery network and stability. AB - A novel design of a multi-drug delivery network and diagnosis using a molecular network is proposed. By using a pair of tweezers to generate the intense optical vortices within the PANDA ring resonator, the required molecules (drug volumes) can be trapped and moved dynamically within the molecular bus networks, in which the required drug delivery targets can be achieved within the network. The advantage of the proposed system is that the diagnostic method can be used within a tiny system (thin film device or circuit), which is available as an embedded device for diagnostic use in patients. In practice, the large molecular networks such as ring, star, and bus networks can be integrated to form a large drug delivery system. The channel spacing of the trapped volumes (molecules) within the bus molecular networks can be provided by using the appropriate free spectrum range, which is analyzed and discussed in the terms of crosstalk effects. In this work, crosstalk effects of about 0.1% are noted, which can be neglected and does not affect the network stability. PMID- 21980239 TI - Reduced adhesion of macrophages on anodized titanium with select nanotube surface features. AB - One of the important prerequisites for a successful orthopedic implant apart from being osteoconductive is the elicitation of a favorable immune response that does not lead to the rejection of the implant by the host tissue. Anodization is one of the simplest surface modification processes used to create nanotextured and nanotubular features on metal oxides which has been shown to improve bone formation. Anodization of titanium (Ti) leads to the formation of TiO(2) nanotubes on the surface, and the presence of these nanotubes mimics the natural nanoscale features of bone, which in turn contributes to improved bone cell attachment, migration, and proliferation. However, inflammatory cell responses on anodized Ti remains to be tested. It is hypothesized that surface roughness and surface feature size on anodized Ti can be carefully manipulated to control immune cell (specifically, macrophages) responses. Here, when Ti samples were anodized at 10 V in the presence of 1% hydrofluoric acid (HF) for 1 minute, nanotextured (nonnanotube) surfaces were created. When anodization of Ti samples was carried out with 1% HF for 10 minutes at 15 V, nanotubes with 40-50 nm diameters were formed, whereas at 20 V with 1% HF for 10 minutes, nanotubes with 60-70 nm diameters were formed. In this study, a reduced density of macrophages was observed after 24 hours of culture on nanotextured and nanotubular Ti samples which were anodized at 10, 15, and 20 V, compared with conventional unmodified Ti samples. This in vitro study thus demonstrated a reduced density of macrophages on anodized Ti, thereby providing further evidence of the greater efficacy of anodized Ti for orthopedic applications. PMID- 21980241 TI - Investigation of the mechanical properties of a low-shrinkage liquid crystalline matrix combined with nano-hydroxyapatite. AB - The objective of this study was to investigate the mechanical properties of a low shrinkage acrylate liquid crystalline resin matrix (ALCRM), (4-3-(acryloyloxy)-2 hydroxypropoxy) phenyl 4-(3-(acryloyloxy)-2-hydroxypropoxy) benzoate, combined with nano-hydroxyapatite (na-HA). The ALCRM monomer and diluent monomer triethylene glycol dimethacrylate (TEGDMA) were mixed at a mass ratio of 7:3 to prepare the resin matrix. The volume shrinkage of the ALCRM/TEGDMA and the traditional resin matrix Bis-GMA (2, 2-bis [4-(3-methacryloxy-2-hydroxypropoxy) phenyl] propane)/TEGDMA were measured. Then 20%, 30%, and 40% na-HA were added to ALCRM/TEGDMA and Bis-GMA/TEGDMA, respectively. Compressive strength (CS) and Vickers hardness (VHN) were tested to identify mechanical properties of the composites. The volume shrinkage of the ALCRM/TEGDMA was 3.60% +/- 0.36%, which was lower than that of the traditional resin matrix. Moreover, with the same amount of na-HA filler, the mechanical properties of the ALCRM-based composites were superior to those of Bis-GMA-based composites. ALCRM-based composites exhibited the highest CS and VHN values when the filler content was 30%. These results indicate that the low-shrinkage liquid crystalline resin matrix has strong mechanical properties after incorporating the na-HA. The experimental ALCRM-based composites have promising potential for the development of novel low shrinkage dental resins with strong mechanical properties. PMID- 21980240 TI - Influence of synthetic superparamagnetic iron oxide on dendritic cells. AB - BACKGROUND: This study investigated the influence of synthetic superparamagnetic iron oxide (SPIO) on dendritic cells and provides a possible method for labeling these cells. METHODS: SPIO nanoparticles were prepared, and their morphology and magnetic properties were characterized. The particles were endocytosed by dendritic cells generated from mouse bone marrow. Labeling efficiency and cellular uptake were analyzed by Prussian blue staining and quantitative spectrophotometric assay. Meanwhile, the surface molecules, cellular apoptosis, and functional properties of the SPIO-labeled dendritic cells were explored by flow cytometry and the mixed lymphocyte reaction assay. RESULTS: The synthetic nanoparticles possessed a spherical shape and good superparamagnetic behavior. The mean concentration of iron in immature and mature dendritic cells was 31.8 +/ 0.7 MUg and 35.6 +/- 1.0 MUg per 1 * 10(6) cells, respectively. After 12 hours of incubation with SPIO at a concentration of 25 MUg/mL, nearly all cells were shown to contain iron. Interestingly, cellular apoptosis and surface expression of CD80, CD86, major histocompatibility II, and chemokine receptor 7 in mature dendritic cells were not affected to any significant extent by SPIO labeling. T cell activation was maintained at a low ratio of dendritic cells to T cells. CONCLUSION: SPIO nanoparticles have good superparamagnetic behavior, highly biocompatible characteristics, and are suitable for use in further study of the migratory behavior and biodistribution of dendritic cells in vivo. PMID- 21980243 TI - Introducing Countercurrents-a new feature of Current Oncology. PMID- 21980244 TI - Early-onset breast cancer: what do we know about the risk factors?: A Countercurrents Series. PMID- 21980242 TI - Metabolic pathway and distribution of superparamagnetic iron oxide nanoparticles: in vivo study. AB - BACKGROUND: Experimental tissue fusion benefits from the selective heating of superparamagnetic iron oxide nanoparticles (SPIONs) under high frequency irradiation. However, the metabolic pathways of SPIONs for tissue fusion remain unknown. Hence, the goal of this in vivo study was to analyze the distribution of SPIONs in different organs by means of magnetic resonance imaging (MRI) and histological analysis after a SPION-containing patch implantation. METHODS: SPION containing patches were implanted in rats. Three animal groups were studied histologically over six months. Degradation assessment of the SPION-albumin patch was performed in vivo using MRI for iron content localization and biodistribution. RESULTS: No SPION degradation or accumulation into the reticuloendothelial system was detected by MRI, MRI relaxometry, or histology, outside the area of the implantation patch. Concentrations from 0.01 MUg/mL to 25 MUg/mL were found to be hyperintense in T1-like gradient echo sequences. The best differentiation of concentrations was found in T2 relaxometry, susceptibility sensitive gradient echo sequences, and in high repetition time T2 images. Qualitative and semiquantitative visualization of small concentrations and accumulation of SPIONs by MRI are feasible. In histological liver samples, Kupffer cells were significantly correlated with postimplantation time, but no differences were observed between sham-treated and induction/no induction groups. Transmission electron microscopy showed local uptake of SPIONs in macrophages and cells of the reticuloendothelial system. Apoptosis staining using caspase showed no increased toxicity compared with sham-treated tissue. Implanted SPION patches were relatively inert with slow, progressive local degradation over the six-month period. No distant structural alterations in the studied tissue could be observed. CONCLUSION: Systemic bioavailability may play a role in specific SPION implant toxicity and therefore the local degradation process is a further aspect to be assessed in future studies. PMID- 21980245 TI - A legal right to die: responding to slippery slope and abuse arguments. PMID- 21980246 TI - Distress-the 6th vital sign. PMID- 21980247 TI - Hyperbaric oxygen for radiation injury: is it indicated? PMID- 21980248 TI - Saccharin deemed "not hazardous" in United States and abroad. PMID- 21980249 TI - Hyperbaric oxygen therapy for late radiation tissue injury in gynecologic malignancies. AB - BACKGROUND: Late radiation tissue injury is a serious complication of radiotherapy for patients with gynecologic malignancies. Strategies for managing pain and other clinical features have limited efficacy; however, hyperbaric oxygen therapy (HBO(2)) may be an effective option for some patients. METHODS: In a systematic review of the literature, the Ovid medline, embase, Cochrane Library, National Guidelines Clearinghouse, and Canadian Medical Association Infobase databases were searched to June 2009 for clinical practice guidelines, systematic reviews, randomized controlled trials, or other relevant evidence. Studies that did not evaluate soft tissue necrosis, cystitis, proctitis, bone necrosis, and other complications were excluded. RESULTS: Two randomized trials, eleven nonrandomized studies, and five supporting documents comprise the evidence base. In addition, information on the harms and safety of treatment with HBO(2) were reported in three additional sources. There is modest direct evidence and emerging indirect evidence that the use of HBO(2) is broadly effective for late radiation tissue injury of the pelvis in women treated for gynecologic malignancies. CONCLUSIONS: Based on the evidence and expert consensus opinion, HBO(2) is likely effective for late radiation tissue injury of the pelvis, with demonstrated efficacy specifically for radiation damage to the anus and rectum;the main indication for HBO(2) therapy in gynecologic oncology is in the management of otherwise refractory chronic radiation injury;HBO(2) may provide symptomatic benefit in certain clinical settings (for example, cystitis, soft tissue necrosis, and osteonecrosis); andHBO(2) may reduce the complications of gynecologic surgery in patients undergoing surgical removal of necrosis. PMID- 21980251 TI - The role of transglutaminases in the pathophysiology of prostate cancer. PMID- 21980250 TI - Multidisciplinary Canadian consensus recommendations for the management and treatment of hepatocellular carcinoma. AB - Globally, hepatocellular carcinoma (hcc) is the third most common cause of death from cancer, after lung and stomach cancer. The incidence of hcc in Canada is increasing and is expected to continue to increase over the next decade. Given the high mortality rate associated with hcc, steps are required to mitigate the impact of the disease. To address this challenging situation, a panel of 17 hcc experts, representing gastroenterologists, hepatologists, hepatobiliary surgeons, medical oncologists, pathologists, and radiologists from across Canada, convened to provide a framework that, using an evidence-based approach, will assist clinicians in optimizing the management and treatment of hcc. The recommendations, summarized here, were developed based on a rigorous methodology in a pre-specified process that was overseen by the steering committee. Specific topics were identified by the steering committee and delegated to a group of content experts within the expert panel, who then systematically reviewed the literature on that topic and drafted the related content and recommendations. The set of recommendations for each topic were reviewed and assigned a level of evidence and grade according to the levels of evidence set out by the Centre for Evidence-based Medicine, Oxford, United Kingdom. Agreement on the level of evidence for each recommendation was achieved by consensus. Consensus was defined as agreement by a two-thirds majority of the 17 members of the expert panel. Recommendations were subject to iterative review and modification by the expert panel until consensus could be achieved. PMID- 21980252 TI - Array comparative genomic hybridization and cytogenetic analysis in pediatric acute leukemias. AB - Most patients with acute lymphocytic leukemia (all) are reported to have acquired chromosomal abnormalities in their leukemic bone marrow cells. Many established chromosome rearrangements have been described, and their associations with specific clinical, biologic, and prognostic features are well defined. However, approximately 30% of pediatric and 50% of adult patients with all do not have cytogenetic abnormalities of clinical significance. Despite significant improvements in outcome for pediatric all, therapy fails in approximately 25% of patients, and these failures often occur unpredictably in patients with a favorable prognosis and "good" cytogenetics at diagnosis.It is well known that karyotype analysis in hematologic malignancies, although genome-wide, is limited because of altered cell kinetics (mitotic rate), a propensity of leukemic blasts to undergo apoptosis in culture, overgrowth by normal cells, and chromosomes of poor quality in the abnormal clone. Array comparative genomic hybridization (acgh "microarray") has a greatly increased genomic resolution over classical cytogenetics. Cytogenetic microarray, which uses genomic dna, is a powerful tool in the analysis of unbalanced chromosome rearrangements, such as copy number gains and losses, and it is the method of choice when the mitotic index is low and the quality of metaphases is suboptimal. The copy number profile obtained by microarray is often called a "molecular karyotype."In the present study, microarray was applied to 9 retrospective cases of pediatric all either with initial high-risk features or with at least 1 relapse. The conventional karyotype was compared to the "molecular karyotype" to assess abnormalities as interpreted by classical cytogenetics. Not only were previously undetected chromosome losses and gains identified by microarray, but several karyotypes interpreted by classical cytogenetics were shown to be discordant with the microarray results. The complementary use of microarray and conventional cytogenetics would allow for more sensitive, comprehensive, and accurate analysis of the underlying genetic profile, with concomitant improvement in prognosis and treatment, not only for pediatric all, but for neoplastic disorders in general. PMID- 21980253 TI - Caring for survivors of breast cancer: perspective of the primary care physician. AB - BACKGROUND AND OBJECTIVES: Increasing numbers of women are surviving breast cancer, and survivorship care is becoming more complex. Primary care physicians provide care for most survivors of breast cancer in the Canadian province of British Columbia. The present study offers insight into the confidence of primary care physicians in their abilities to provide such care. It also explores potential ways to assist those providers in enhancing this aspect of their practice. METHODS: A questionnaire was mailed to 1000 primary care physicians caring for survivors of breast cancer. The questionnaire explored the perspectives of the responding physicians on their ability to manage various aspects of survivorship care for breast cancer patients, identified preferences for the content and format of communication from oncologists at the time of transition from active oncology treatment to survivorship, and determined the means most commonly used to obtain knowledge about breast cancer. This 1-page, 31 item checkbox and open-answer questionnaire assessed the perceptions of primary care physicians about the care of breast cancer survivors after completion of active treatment and their personal preferences for resources providing information about breast cancer. RESULTS: The questionnaire response rate was 59%. Primary care physicians reported being most confident in screening for recurrence and managing patient anxiety; they were least confident in managing lymphedema and providing psychosocial counselling. Compared with physicians following fewer survivors of breast cancer, those who followed more breast cancer survivors had higher confidence in managing the biomedical aspects of follow-up and in providing counselling about nutrition and exercise. Most physicians found discharge letters from oncologists to be useful. Point-form discharge information was preferred by 43%; detailed description, by 19%; and both formats, by 38%. The most useful information items identified for inclusion in a discharge letter were a diagnosis and treatment summary and the recommended surveillance and endocrine therapy. Continuing medical education events and online resources were the means most commonly used to obtain knowledge about breast cancer. CONCLUSIONS: Primary care physicians who provide follow-up for survivors of breast cancer report that they are confident in managing care and satisfied with discharge letters containing a diagnosis and treatment summary, and recommendations for surveillance and endocrine treatment. At the time of patient discharge, additional information about common medical and psychosocial issues in this patient population would be useful to primary care physicians. Preferred means to access current breast cancer information include continuing medical education events and online resources. PMID- 21980254 TI - Health care strategies to promote earlier presentation of symptomatic breast cancer: perspectives of women and family physicians. AB - BACKGROUND: Many women with symptoms suggestive of a breast cancer diagnosis delay presentation to their family physician. Although factors associated with delay have been well described, there is a paucity of data on strategies to mitigate delay. OBJECTIVES: We conducted a qualitative research project to examine factors related to delay and to identify health care system changes that might encourage earlier presentation. METHODS: Individual semi-structured interviews were conducted with women who sought care 12 weeks or more after self detection of breast cancer symptoms and with family physicians whose practices included patients meeting that criterion. RESULTS: The women and physicians both suggested a need for clearer screening mammography guidelines for women 40-49 years of age and for better messaging concerning breast awareness. The use of additional hopeful testimonials from breast cancer survivors were suggested to help dispel the notion of cancer as a "death sentence." Educational initiatives were proposed, aimed at both increasing awareness of "non-lump" breast cancer symptoms and advising women that a previous benign diagnosis does not ensure that future symptoms are not cancer. Women wanted empathic nonjudgmental access to care. Improved methods to track compliance with screening mammography and with periodic health exams and access to a rapid diagnostic process were suggested. CONCLUSIONS: A list of "at-risk situations for delay" in diagnosis of breast cancer was developed for physicians to assist in identifying women who might delay. Health care system changes actionable both at the health policy level and in the family physician's office were identified to encourage earlier presentation of women with symptomatic breast cancer. PMID- 21980255 TI - Survival and treatment patterns in elderly patients with advanced non-small-cell lung cancer in Manitoba. AB - Lung cancer is the leading cause of cancer death worldwide. Non-small-cell lung cancer (nsclc) is the most common form of lung cancer, with a median age at diagnosis of 70 years. These elderly patients are often underrepresented in the randomized clinical trials upon which chemotherapy plans are based. The objective of the present study was to determine the patterns of treatment and survival in elderly patients with advanced nsclc in Manitoba.An eligible cohort of elderly patients over 70 years of age at diagnosis (n = 497) with advanced nsclc was identified from the provincial cancer registry database for the period 2001-2004. Of the 497 patients identified, only 147 had been evaluated by a medical oncologist, and 82 of the 147 had received chemotherapy treatment, which is 16.5% of the initial cohort.Patients who received chemotherapy were younger than those who did not receive chemotherapy. Most patients receiving chemotherapy (84%) received doublet chemotherapy, with an almost equal split between cisplatin and carboplatin treatment. The median survival times for patients in this cohort were 64 weeks (stage iii nsclc) and 56 weeks (stage iv) with chemotherapy treatment, and 46 weeks (stage iii) and 26 weeks (stage iv) without chemotherapy.Although 50% of patients with advanced nsclc are more than 70 years of age, few are evaluated by a medical oncologist and even fewer are treated with chemotherapy. However, it should be noted that, in the elderly patients who were treated, survival times are comparable to those experienced by younger patients, which is indicative of a benefit of chemotherapy treatment for those elderly patients. PMID- 21980256 TI - Establishing a multicentre clinical research network: lessons learned. AB - BACKGROUND: Within many health care disciplines, research networks have emerged to connect researchers who are physically separated, to facilitate sharing of expertise and resources, and to exchange valuable skills. A multicentre research network committed to studying difficult cancer pain problems was launched in 2004 as part of a Canadian initiative to increase palliative and end-of-life care research capacity. Funding was received for 5 years to support network activities. METHODS: Mid-way through the 5-year granting period, an external review panel provided a formal mid-grant evaluation. Concurrently, an internal evaluation of the network by survey of its members was conducted. Based on feedback from both evaluations and on a review of the literature, we identified several components believed to be relevant to the development of a successful clinical cancer research network. RESULTS: THESE COMMON ELEMENTS OF SUCCESSFUL CLINICAL CANCER RESEARCH NETWORKS WERE IDENTIFIED: shared vision, formal governance policies and terms of reference, infrastructure support, regular and effective communication, an accountability framework, a succession planning strategy to address membership change over time, multiple strategies to engage network members, regular review of goals and timelines, and a balance between structure and creativity. CONCLUSIONS: In establishing and conducting a multi year, multicentre clinical cancer research network, network members were led to reflect on the factors that contributed most to the achievement of network goals. Several specific factors were identified that seemed to be highly relevant in promoting success. These observations are presented to foster further discussion on the successful design and operation of research networks. PMID- 21980257 TI - Canadian College of Medical Geneticists guidelines for the indications, analysis, and reporting of cancer specimens. AB - The Canadian College of Medical Geneticists (ccmg) is a national organization of medical and laboratory geneticists. The mission of the ccmg is to establish and maintain high-quality professional and ethical standards for medical genetics services in Canada and to help to ensure that service of the highest quality is delivered to the Canadian public.Cancer cytogenetics is one of the sections of practice of the ccmg. The ccmg Cytogenetic Committee has, therefore, put forward guidelines to provide oncologists and ccmg cytogeneticists with a comprehensive review of the cytogenetic diagnostic tests that are recommended as a minimum standard of care for tumours of hematopoietic and lymphoid tissues and for tumours of soft tissue and bone. The guidelines were approved by the ccmg board of directors in June 2010. PMID- 21980258 TI - Durable remission of inoperable liver metastasis from rectal cancer after hepatic arterial infusion of oxaliplatin and 5-fluorouracil in combination with intravenous cetuximab. AB - At diagnosis of a cT3N0M1 adenocarcinoma of the rectum with synchronous inoperable liver metastases, a 59-year-old man was treated with preoperative radiotherapy (5*5 Gy), followed by laparoscopy-assisted anterior resection of the rectum with total mesorectal excision. At the first postoperative evaluation, a new lung metastasis was detected. First-line chemotherapy with folfiri (5 fluorouracil, irinotecan, leucovorin) resulted in transient stabilization of the metastatic liver disease. At progression, oxaliplatin and 5-fluorouracil-folinic acid were administered by intrahepatic arterial infusion, in combination with intravenous cetuximab. A partial radiologic response was obtained, with complete metabolic response on fluorodeoxyglucose positron-emission tomography, and normalization of carcinoembryonic antigen values. The solitary lung metastasis was sequentially treated with radiotherapy and resection. Five years after the initial diagnosis, this patient remains free from progression, with residual cystic remnants of the liver metastases visible on conventional computed tomography imaging, but not enhancing with fluorodeoxyglucose positron-emission tomography. PMID- 21980259 TI - The Internal Structure and Ecological Context of Coparenting: A Framework for Research and Intervention. AB - Research on coparenting has grown over the past decade, supporting a view of coparenting as a central element of family life that influences parental adjustment, parenting, and child outcomes. This article introduces a multi-domain conception of coparenting that organizes existing research and paves the way for future research and intervention. This article advances a conceptualization of how coparenting domains influence parental adjustment, parenting, and child adjustment. An ecological model that outlines influences on coparenting relationships, as well as mediating and moderating pathways, is described. Areas of future research in the developmental course of coparenting relationships are noted. PMID- 21980260 TI - The Role of the Self in Responses to Health Communications: A Cultural Perspective. AB - To the extent that cultures vary in how they shape individuals' self-construal, it is important to consider a cultural perspective to understand the role of the self in health persuasion. We review recent research that has adopted a cultural perspective on how to frame health communications to be congruent with important, culturally variant, aspects of the self. Matching features of a health message to approach vs. avoidance orientation and independent vs. interdependent self construal can lead to greater message acceptance and health behavior change. Discussion centers on the theoretical and applied value of the self as an organizing framework for constructing persuasive health communications. PMID- 21980261 TI - Nuclear receptor DHR4 controls the timing of steroid hormone pulses during Drosophila development. AB - In insects, precisely timed periodic pulses of the molting hormone ecdysone control major developmental transitions such as molts and metamorphosis. The synthesis and release of ecdysone, a steroid hormone, is itself controlled by PTTH (prothoracicotopic hormone). PTTH transcript levels oscillate with an 8 h rhythm, but its significance regarding the timing of ecdysone pulses is unclear. PTTH acts on its target tissue, the prothoracic gland (PG), by activating the Ras/Raf/ERK pathway through its receptor Torso, however direct targets of this pathway have yet to be identified. Here, we demonstrate that Drosophila Hormone Receptor 4 (DHR4), a nuclear receptor, is a key target of the PTTH pathway and establishes temporal boundaries by terminating ecdysone pulses. Specifically, we show that DHR4 oscillates between the nucleus and cytoplasm of PG cells, and that the protein is absent from PG nuclei at developmental times when low titer ecdysone pulses occur. This oscillatory behavior is blocked when PTTH or torso function is abolished, resulting in nuclear accumulation of DHR4, while hyperactivating the PTTH pathway results in cytoplasmic retention of the protein. Increasing DHR4 levels in the PG can delay or arrest development. In contrast, reducing DHR4 function in the PG triggers accelerated development, which is caused by precocious ecdysone signaling due to a failure to repress ecdysone pulses. Finally, we show that DHR4 negatively regulates the expression of a hitherto uncharacterized cytochrome P450 gene, Cyp6t3. Disruption of Cyp6t3 function causes low ecdysteroid titers and results in heterochronic phenotypes and molting defects, indicating a novel role in the ecdysone biosynthesis pathway. We propose a model whereby nuclear DHR4 controls the duration of ecdysone pulses by negatively regulating ecdysone biosynthesis through repression of Cyp6t3, and that this repressive function is temporarily overturned via the PTTH pathway by removing DHR4 from the nuclear compartment. PMID- 21980262 TI - Individual actin filaments in a microfluidic flow reveal the mechanism of ATP hydrolysis and give insight into the properties of profilin. AB - The hydrolysis of ATP associated with actin and profilin-actin polymerization is pivotal in cell motility. It is at the origin of treadmilling of actin filaments and controls their dynamics and mechanical properties, as well as their interactions with regulatory proteins. The slow release of inorganic phosphate (Pi) that follows rapid cleavage of ATP gamma phosphate is linked to an increase in the rate of filament disassembly. The mechanism of Pi release in actin filaments has remained elusive for over 20 years. Here, we developed a microfluidic setup to accurately monitor the depolymerization of individual filaments and determine their local ADP-Pi content. We demonstrate that Pi release in the filament is not a vectorial but a random process with a half-time of 102 seconds, irrespective of whether the filament is assembled from actin or profilin-actin. Pi release from the depolymerizing barbed end is faster (half time of 0.39 seconds) and further accelerated by profilin. Profilin accelerates the depolymerization of both ADP- and ADP-Pi-F-actin. Altogether, our data show that during elongation from profilin-actin, the dissociation of profilin from the growing barbed end is not coupled to Pi release or to ATP cleavage on the terminal subunit. These results emphasize the potential of microfluidics in elucidating actin regulation at the scale of individual filaments. PMID- 21980264 TI - How actin filaments doff their Pi cap. PMID- 21980263 TI - Mesenchymal transition and dissemination of cancer cells is driven by myeloid derived suppressor cells infiltrating the primary tumor. AB - In order to metastasize, cancer cells need to acquire a motile phenotype. Previously, development of this phenotype was thought to rely on the acquisition of selected, random mutations and thus would occur late in cancer progression. However, recent studies show that cancer cells disseminate early, implying the existence of a different, faster route to the metastatic motile phenotype. Using a spontaneous murine model of melanoma, we show that a subset of bone marrow derived immune cells (myeloid-derived suppressor cells or MDSC) preferentially infiltrates the primary tumor and actively promotes cancer cell dissemination by inducing epithelial-mesenchymal transition (EMT). CXCL5 is the main chemokine attracting MDSC to the primary tumor. In vitro assay using purified MDSC showed that TGF-beta, EGF, and HGF signaling pathways are all used by MDSC to induce EMT in cancer cells. These findings explain how cancer cells acquire a motile phenotype so early and provide a mechanistic explanation for the long recognized link between inflammation and cancer progression. PMID- 21980265 TI - Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. AB - BACKGROUND: Randomised trials have highlighted the cardiovascular risks of non steroidal anti-inflammatory drugs (NSAIDs) in high doses and sometimes atypical settings. Here, we provide estimates of the comparative risks with individual NSAIDs at typical doses in community settings. METHODS AND FINDINGS: We performed a systematic review of community-based controlled observational studies. We conducted comprehensive literature searches, extracted adjusted relative risk (RR) estimates, and pooled the estimates for major cardiovascular events associated with use of individual NSAIDs, in different doses, and in populations with low and high background risks of cardiovascular events. We also compared individual drugs in pair-wise (within study) analyses, generating ratios of RRs (RRRs). Thirty case-control studies included 184,946 cardiovascular events, and 21 cohort studies described outcomes in >2.7 million exposed individuals. Of the extensively studied drugs (ten or more studies), the highest overall risks were seen with rofecoxib, 1.45 (95% CI 1.33, 1.59), and diclofenac, 1.40 (1.27, 1.55), and the lowest with ibuprofen, 1.18 (1.11, 1.25), and naproxen, 1.09 (1.02, 1.16). In a sub-set of studies, risk was elevated with low doses of rofecoxib, 1.37 (1.20, 1.57), celecoxib, 1.26 (1.09, 1.47), and diclofenac, 1.22 (1.12, 1.33), and rose in each case with higher doses. Ibuprofen risk was seen only with higher doses. Naproxen was risk-neutral at all doses. Of the less studied drugs etoricoxib, 2.05 (1.45, 2.88), etodolac, 1.55 (1.28, 1.87), and indomethacin, 1.30 (1.19, 1.41), had the highest risks. In pair-wise comparisons, etoricoxib had a higher RR than ibuprofen, RRR = 1.68 (99% CI 1.14, 2.49), and naproxen, RRR = 1.75 (1.16, 2.64); etodolac was not significantly different from naproxen and ibuprofen. Naproxen had a significantly lower risk than ibuprofen, RRR = 0.92 (0.87, 0.99). RR estimates were constant with different background risks for cardiovascular disease and rose early in the course of treatment. CONCLUSIONS: This review suggests that among widely used NSAIDs, naproxen and low-dose ibuprofen are least likely to increase cardiovascular risk. Diclofenac in doses available without prescription elevates risk. The data for etoricoxib were sparse, but in pair-wise comparisons this drug had a significantly higher RR than naproxen or ibuprofen. Indomethacin is an older, rather toxic drug, and the evidence on cardiovascular risk casts doubt on its continued clinical use. Please see later in the article for the Editors' Summary. PMID- 21980266 TI - Setting research priorities to reduce global mortality from childhood pneumonia by 2015. PMID- 21980267 TI - Dynamics and mechanical stability of the developing dorsoventral organizer of the wing imaginal disc. AB - Shaping the primordia during development relies on forces and mechanisms able to control cell segregation. In the imaginal discs of Drosophila the cellular populations that will give rise to the dorsal and ventral parts on the wing blade are segregated and do not intermingle. A cellular population that becomes specified by the boundary of the dorsal and ventral cellular domains, the so called organizer, controls this process. In this paper we study the dynamics and stability of the dorsal-ventral organizer of the wing imaginal disc of Drosophila as cell proliferation advances. Our approach is based on a vertex model to perform in silico experiments that are fully dynamical and take into account the available experimental data such as: cell packing properties, orientation of the cellular divisions, response upon membrane ablation, and robustness to mechanical perturbations induced by fast growing clones. Our results shed light on the complex interplay between the cytoskeleton mechanics, the cell cycle, the cell growth, and the cellular interactions in order to shape the dorsal-ventral organizer as a robust source of positional information and a lineage controller. Specifically, we elucidate the necessary and sufficient ingredients that enforce its functionality: distinctive mechanical properties, including increased tension, longer cell cycle duration, and a cleavage criterion that satisfies the Hertwig rule. Our results provide novel insights into the developmental mechanisms that drive the dynamics of the DV organizer and set a definition of the so-called Notch fence model in quantitative terms. PMID- 21980268 TI - A mathematical model of muscle containing heterogeneous half-sarcomeres exhibits residual force enhancement. AB - A skeletal muscle fiber that is stimulated to contract and then stretched from L1 to L2 produces more force after the initial transient decays than if it is stimulated at L2. This behavior has been well studied experimentally, and is known as residual force enhancement. The underlying mechanism remains controversial. We hypothesized that residual force enhancement could reflect mechanical interactions between heterogeneous half-sarcomeres. To test this hypothesis, we subjected a computational model of interacting heterogeneous half sarcomeres to the same activation and stretch protocols that produce residual force enhancement in real preparations. Following a transient period of elevated force associated with active stretching, the model predicted a slowly decaying force enhancement lasting >30 seconds after stretch. Enhancement was on the order of 13% above isometric tension at the post-stretch muscle length, which agrees well with experimental measurements. Force enhancement in the model was proportional to stretch magnitude but did not depend strongly on the velocity of stretch, also in agreement with experiments. Even small variability in the strength of half-sarcomeres (2.1% standard deviation, normally distributed) was sufficient to produce a 5% force enhancement over isometric tension. Analysis of the model suggests that heterogeneity in half-sarcomeres leads to residual force enhancement by storing strain energy introduced during active stretch in distributions of bound cross-bridges. Complex interactions between the heterogeneous half-sarcomeres then dissipate this stored energy at a rate much slower than isolated cross-bridges would cycle. Given the variations in half sarcomere length that have been observed in real muscle preparations and the stochastic variability inherent in all biological systems, half-sarcomere heterogeneity cannot be excluded as a contributing source of residual force enhancement. PMID- 21980269 TI - A model for the origin and properties of flicker-induced geometric phosphenes. AB - We present a model for flicker phosphenes, the spontaneous appearance of geometric patterns in the visual field when a subject is exposed to diffuse flickering light. We suggest that the phenomenon results from interaction of cortical lateral inhibition with resonant periodic stimuli. We find that the best temporal frequency for eliciting phosphenes is a multiple of intrinsic (damped) oscillatory rhythms in the cortex. We show how both the quantitative and qualitative aspects of the patterns change with frequency of stimulation and provide an explanation for these differences. We use Floquet theory combined with the theory of pattern formation to derive the parameter regimes where the phosphenes occur. We use symmetric bifurcation theory to show why low frequency flicker should produce hexagonal patterns while high frequency produces pinwheels, targets, and spirals. PMID- 21980270 TI - A multi-compartment model for interneurons in the dorsal lateral geniculate nucleus. AB - GABAergic interneurons (INs) in the dorsal lateral geniculate nucleus (dLGN) shape the information flow from retina to cortex, presumably by controlling the number of visually evoked spikes in geniculate thalamocortical (TC) neurons, and refining their receptive field. The INs exhibit a rich variety of firing patterns: Depolarizing current injections to the soma may induce tonic firing, periodic bursting or an initial burst followed by tonic spiking, sometimes with prominent spike-time adaptation. When released from hyperpolarization, some INs elicit rebound bursts, while others return more passively to the resting potential. A full mechanistic understanding that explains the function of the dLGN on the basis of neuronal morphology, physiology and circuitry is currently lacking. One way to approach such an understanding is by developing a detailed mathematical model of the involved cells and their interactions. Limitations of the previous models for the INs of the dLGN region prevent an accurate representation of the conceptual framework needed to understand the computational properties of this region. We here present a detailed compartmental model of INs using, for the first time, a morphological reconstruction and a set of active dendritic conductances constrained by experimental somatic recordings from INs under several different current-clamp conditions. The model makes a number of experimentally testable predictions about the role of specific mechanisms for the firing properties observed in these neurons. In addition to accounting for the significant features of all experimental traces, it quantitatively reproduces the experimental recordings of the action-potential- firing frequency as a function of injected current. We show how and why relative differences in conductance values, rather than differences in ion channel composition, could account for the distinct differences between the responses observed in two different neurons, suggesting that INs may be individually tuned to optimize network operation under different input conditions. PMID- 21980271 TI - Long-range intra-protein communication can be transmitted by correlated side chain fluctuations alone. AB - Allosteric regulation is a key component of cellular communication, but the way in which information is passed from one site to another within a folded protein is not often clear. While backbone motions have long been considered essential for long-range information conveyance, side-chain motions have rarely been considered. In this work, we demonstrate their potential utility using Monte Carlo sampling of side-chain torsional angles on a fixed backbone to quantify correlations amongst side-chain inter-rotameric motions. Results indicate that long-range correlations of side-chain fluctuations can arise independently from several different types of interactions: steric repulsions, implicit solvent interactions, or hydrogen bonding and salt-bridge interactions. These robust correlations persist across the entire protein (up to 60 A in the case of calmodulin) and can propagate long-range changes in side-chain variability in response to single residue perturbations. PMID- 21980272 TI - LsrR quorum sensing "switch" is revealed by a bottom-up approach. AB - Quorum sensing (QS) enables bacterial multicellularity and selective advantage for communicating populations. While genetic "switching" phenomena are a common feature, their mechanistic underpinnings have remained elusive. The interplay between circuit components and their regulation are intertwined and embedded. Observable phenotypes are complex and context dependent. We employed a combination of experimental work and mathematical models to decipher network connectivity and signal transduction in the autoinducer-2 (AI-2) quorum sensing system of E. coli. Negative and positive feedback mechanisms were examined by separating the network architecture into sub-networks. A new unreported negative feedback interaction was hypothesized and tested via a simple mathematical model. Also, the importance of the LsrR regulator and its determinant role in the E. coli QS "switch", normally masked by interfering regulatory loops, were revealed. Our simple model allowed mechanistic understanding of the interplay among regulatory sub-structures and their contributions to the overall native functioning network. This "bottom up" approach in understanding gene regulation will serve to unravel complex QS network architectures and lead to the directed coordination of emergent behaviors. PMID- 21980273 TI - The effect of heterogeneity on invasion in spatial epidemics: from theory to experimental evidence in a model system. AB - Heterogeneity in host populations is an important factor affecting the ability of a pathogen to invade, yet the quantitative investigation of its effects on epidemic spread is still an open problem. In this paper, we test recent theoretical results, which extend the established "percolation paradigm" to the spread of a pathogen in discrete heterogeneous host populations. In particular, we test the hypothesis that the probability of epidemic invasion decreases when host heterogeneity is increased. We use replicated experimental microcosms, in which the ubiquitous pathogenic fungus Rhizoctonia solani grows through a population of discrete nutrient sites on a lattice, with nutrient sites representing hosts. The degree of host heterogeneity within different populations is adjusted by changing the proportion and the nutrient concentration of nutrient sites. The experimental data are analysed via Bayesian inference methods, estimating pathogen transmission parameters for each individual population. We find a significant, negative correlation between heterogeneity and the probability of pathogen invasion, thereby validating the theory. The value of the correlation is also in remarkably good agreement with the theoretical predictions. We briefly discuss how our results can be exploited in the design and implementation of disease control strategies. PMID- 21980274 TI - Smart swarms of bacteria-inspired agents with performance adaptable interactions. AB - Collective navigation and swarming have been studied in animal groups, such as fish schools, bird flocks, bacteria, and slime molds. Computer modeling has shown that collective behavior of simple agents can result from simple interactions between the agents, which include short range repulsion, intermediate range alignment, and long range attraction. Here we study collective navigation of bacteria-inspired smart agents in complex terrains, with adaptive interactions that depend on performance. More specifically, each agent adjusts its interactions with the other agents according to its local environment--by decreasing the peers' influence while navigating in a beneficial direction, and increasing it otherwise. We show that inclusion of such performance dependent adaptable interactions significantly improves the collective swarming performance, leading to highly efficient navigation, especially in complex terrains. Notably, to afford such adaptable interactions, each modeled agent requires only simple computational capabilities with short-term memory, which can easily be implemented in simple swarming robots. PMID- 21980275 TI - Protein networks as logic functions in development and cancer. AB - Many biological and clinical outcomes are based not on single proteins, but on modules of proteins embedded in protein networks. A fundamental question is how the proteins within each module contribute to the overall module activity. Here, we study the modules underlying three representative biological programs related to tissue development, breast cancer metastasis, or progression of brain cancer, respectively. For each case we apply a new method, called Network-Guided Forests, to identify predictive modules together with logic functions which tie the activity of each module to the activity of its component genes. The resulting modules implement a diverse repertoire of decision logic which cannot be captured using the simple approximations suggested in previous work such as gene summation or subtraction. We show that in cancer, certain combinations of oncogenes and tumor suppressors exert competing forces on the system, suggesting that medical genetics should move beyond cataloguing individual cancer genes to cataloguing their combinatorial logic. PMID- 21980276 TI - War of ontology worlds: mathematics, computer code, or Esperanto? AB - The use of structured knowledge representations-ontologies and terminologies-has become standard in biomedicine. Definitions of ontologies vary widely, as do the values and philosophies that underlie them. In seeking to make these views explicit, we conducted and summarized interviews with a dozen leading ontologists. Their views clustered into three broad perspectives that we summarize as mathematics, computer code, and Esperanto. Ontology as mathematics puts the ultimate premium on rigor and logic, symmetry and consistency of representation across scientific subfields, and the inclusion of only established, non-contradictory knowledge. Ontology as computer code focuses on utility and cultivates diversity, fitting ontologies to their purpose. Like computer languages C++, Prolog, and HTML, the code perspective holds that diverse applications warrant custom designed ontologies. Ontology as Esperanto focuses on facilitating cross-disciplinary communication, knowledge cross-referencing, and computation across datasets from diverse communities. We show how these views align with classical divides in science and suggest how a synthesis of their concerns could strengthen the next generation of biomedical ontologies. PMID- 21980277 TI - A single-rate context-dependent learning process underlies rapid adaptation to familiar object dynamics. AB - Motor learning has been extensively studied using dynamic (force-field) perturbations. These induce movement errors that result in adaptive changes to the motor commands. Several state-space models have been developed to explain how trial-by-trial errors drive the progressive adaptation observed in such studies. These models have been applied to adaptation involving novel dynamics, which typically occurs over tens to hundreds of trials, and which appears to be mediated by a dual-rate adaptation process. In contrast, when manipulating objects with familiar dynamics, subjects adapt rapidly within a few trials. Here, we apply state-space models to familiar dynamics, asking whether adaptation is mediated by a single-rate or dual-rate process. Previously, we reported a task in which subjects rotate an object with known dynamics. By presenting the object at different visual orientations, adaptation was shown to be context-specific, with limited generalization to novel orientations. Here we show that a multiple context state-space model, with a generalization function tuned to visual object orientation, can reproduce the time-course of adaptation and de-adaptation as well as the observed context-dependent behavior. In contrast to the dual-rate process associated with novel dynamics, we show that a single-rate process mediates adaptation to familiar object dynamics. The model predicts that during exposure to the object across multiple orientations, there will be a degree of independence for adaptation and de-adaptation within each context, and that the states associated with all contexts will slowly de-adapt during exposure in one particular context. We confirm these predictions in two new experiments. Results of the current study thus highlight similarities and differences in the processes engaged during exposure to novel versus familiar dynamics. In both cases, adaptation is mediated by multiple context-specific representations. In the case of familiar object dynamics, however, the representations can be engaged based on visual context, and are updated by a single-rate process. PMID- 21980278 TI - Time scale hierarchies in the functional organization of complex behaviors. AB - Traditional approaches to cognitive modelling generally portray cognitive events in terms of 'discrete' states (point attractor dynamics) rather than in terms of processes, thereby neglecting the time structure of cognition. In contrast, more recent approaches explicitly address this temporal dimension, but typically provide no entry points into cognitive categorization of events and experiences. With the aim to incorporate both these aspects, we propose a framework for functional architectures. Our approach is grounded in the notion that arbitrary complex (human) behaviour is decomposable into functional modes (elementary units), which we conceptualize as low-dimensional dynamical objects (structured flows on manifolds). The ensemble of modes at an agent's disposal constitutes his/her functional repertoire. The modes may be subjected to additional dynamics (termed operational signals), in particular, instantaneous inputs, and a mechanism that sequentially selects a mode so that it temporarily dominates the functional dynamics. The inputs and selection mechanisms act on faster and slower time scales then that inherent to the modes, respectively. The dynamics across the three time scales are coupled via feedback, rendering the entire architecture autonomous. We illustrate the functional architecture in the context of serial behaviour, namely cursive handwriting. Subsequently, we investigate the possibility of recovering the contributions of functional modes and operational signals from the output, which appears to be possible only when examining the output phase flow (i.e., not from trajectories in phase space or time). PMID- 21980280 TI - Ten simple rules for getting help from online scientific communities. PMID- 21980279 TI - Changes in dynamics upon oligomerization regulate substrate binding and allostery in amino acid kinase family members. AB - Oligomerization is a functional requirement for many proteins. The interfacial interactions and the overall packing geometry of the individual monomers are viewed as important determinants of the thermodynamic stability and allosteric regulation of oligomers. The present study focuses on the role of the interfacial interactions and overall contact topology in the dynamic features acquired in the oligomeric state. To this aim, the collective dynamics of enzymes belonging to the amino acid kinase family both in dimeric and hexameric forms are examined by means of an elastic network model, and the softest collective motions (i.e., lowest frequency or global modes of motions) favored by the overall architecture are analyzed. Notably, the lowest-frequency modes accessible to the individual subunits in the absence of multimerization are conserved to a large extent in the oligomer, suggesting that the oligomer takes advantage of the intrinsic dynamics of the individual monomers. At the same time, oligomerization stiffens the interfacial regions of the monomers and confers new cooperative modes that exploit the rigid-body translational and rotational degrees of freedom of the intact monomers. The present study sheds light on the mechanism of cooperative inhibition of hexameric N-acetyl-L-glutamate kinase by arginine and on the allosteric regulation of UMP kinases. It also highlights the significance of the particular quaternary design in selectively determining the oligomer dynamics congruent with required ligand-binding and allosteric activities. PMID- 21980281 TI - Determinants of the spatiotemporal dynamics of the 2009 H1N1 pandemic in Europe: implications for real-time modelling. AB - Influenza pandemics in the last century were characterized by successive waves and differences in impact and timing between different regions, for reasons not clearly understood. The 2009 H1N1 pandemic showed rapid global spread, but with substantial heterogeneity in timing within each hemisphere. Even within Europe substantial variation was observed, with the UK being unique in experiencing a major first wave of transmission in early summer and all other countries having a single major epidemic in the autumn/winter, with a West to East pattern of spread. Here we show that a microsimulation model, parameterised using data about H1N1pdm collected by the beginning of June 2009, explains the occurrence of two waves in UK and a single wave in the rest of Europe as a consequence of timing of H1N1pdm spread, fluxes of travels from US and Mexico, and timing of school vacations. The model provides a description of pandemic spread through Europe, depending on intra-European mobility patterns and socio-demographic structure of the European populations, which is in broad agreement with observed timing of the pandemic in different countries. Attack rates are predicted to depend on the socio-demographic structure, with age dependent attack rates broadly agreeing with available serological data. Results suggest that the observed heterogeneity can be partly explained by the between country differences in Europe: marked differences in school calendars, mobility patterns and sociodemographic structures. Moreover, higher susceptibility of children to infection played a key role in determining the epidemiology of the 2009 pandemic. Our work shows that it would have been possible to obtain a broad-brush prediction of timing of the European pandemic well before the autumn of 2009, much more difficult to achieve with simpler models or pre-pandemic parameterisation. This supports the use of models accounting for the structure of complex modern societies for giving insight to policy makers. PMID- 21980282 TI - Recurrent signature patterns in HIV-1 B clade envelope glycoproteins associated with either early or chronic infections. AB - Here we have identified HIV-1 B clade Envelope (Env) amino acid signatures from early in infection that may be favored at transmission, as well as patterns of recurrent mutation in chronic infection that may reflect common pathways of immune evasion. To accomplish this, we compared thousands of sequences derived by single genome amplification from several hundred individuals that were sampled either early in infection or were chronically infected. Samples were divided at the outset into hypothesis-forming and validation sets, and we used phylogenetically corrected statistical strategies to identify signatures, systematically scanning all of Env. Signatures included single amino acids, glycosylation motifs, and multi-site patterns based on functional or structural groupings of amino acids. We identified signatures near the CCR5 co-receptor binding region, near the CD4 binding site, and in the signal peptide and cytoplasmic domain, which may influence Env expression and processing. Two signatures patterns associated with transmission were particularly interesting. The first was the most statistically robust signature, located in position 12 in the signal peptide. The second was the loss of an N-linked glycosylation site at positions 413-415; the presence of this site has been recently found to be associated with escape from potent and broad neutralizing antibodies, consistent with enabling a common pathway for immune escape during chronic infection. Its recurrent loss in early infection suggests it may impact fitness at the time of transmission or during early viral expansion. The signature patterns we identified implicate Env expression levels in selection at viral transmission or in early expansion, and suggest that immune evasion patterns that recur in many individuals during chronic infection when antibodies are present can be selected against when the infection is being established prior to the adaptive immune response. PMID- 21980283 TI - Quantitative in vivo analyses reveal calcium-dependent phosphorylation sites and identifies a novel component of the Toxoplasma invasion motor complex. AB - Apicomplexan parasites depend on the invasion of host cells for survival and proliferation. Calcium-dependent signaling pathways appear to be essential for micronemal release and gliding motility, yet the target of activated kinases remains largely unknown. We have characterized calcium-dependent phosphorylation events during Toxoplasma host cell invasion. Stimulation of live tachyzoites with Ca2+-mobilizing drugs leads to phosphorylation of numerous parasite proteins, as shown by differential 2-DE display of 32[P]-labeled protein extracts. Multi dimensional Protein Identification Technology (MudPIT) identified ~546 phosphorylation sites on over 300 Toxoplasma proteins, including 10 sites on the actomyosin invasion motor. Using a Stable Isotope of Amino Acids in Culture (SILAC)-based quantitative LC-MS/MS analyses we monitored changes in the abundance and phosphorylation of the invasion motor complex and defined Ca2+ dependent phosphorylation patterns on three of its components--GAP45, MLC1 and MyoA. Furthermore, calcium-dependent phosphorylation of six residues across GAP45, MLC1 and MyoA is correlated with invasion motor activity. By analyzing proteins that appear to associate more strongly with the invasion motor upon calcium stimulation we have also identified a novel 15-kDa Calmodulin-like protein that likely represents the MyoA Essential Light Chain of the Toxoplasma invasion motor. This suggests that invasion motor activity could be regulated not only by phosphorylation but also by the direct binding of calcium ions to this new component. PMID- 21980284 TI - High-resolution phenotypic profiling defines genes essential for mycobacterial growth and cholesterol catabolism. AB - The pathways that comprise cellular metabolism are highly interconnected, and alterations in individual enzymes can have far-reaching effects. As a result, global profiling methods that measure gene expression are of limited value in predicting how the loss of an individual function will affect the cell. In this work, we employed a new method of global phenotypic profiling to directly define the genes required for the growth of Mycobacterium tuberculosis. A combination of high-density mutagenesis and deep-sequencing was used to characterize the composition of complex mutant libraries exposed to different conditions. This allowed the unambiguous identification of the genes that are essential for Mtb to grow in vitro, and proved to be a significant improvement over previous approaches. To further explore functions that are required for persistence in the host, we defined the pathways necessary for the utilization of cholesterol, a critical carbon source during infection. Few of the genes we identified had previously been implicated in this adaptation by transcriptional profiling, and only a fraction were encoded in the chromosomal region known to encode sterol catabolic functions. These genes comprise an unexpectedly large percentage of those previously shown to be required for bacterial growth in mouse tissue. Thus, this single nutritional change accounts for a significant fraction of the adaption to the host. This work provides the most comprehensive genetic characterization of a sterol catabolic pathway to date, suggests putative roles for uncharacterized virulence genes, and precisely maps genes encoding potential drug targets. PMID- 21980285 TI - The human papillomavirus E6 oncogene represses a cell adhesion pathway and disrupts focal adhesion through degradation of TAp63beta upon transformation. AB - Cervical carcinomas result from cellular transformation by the human papillomavirus (HPV) E6 and E7 oncogenes which are constitutively expressed in cancer cells. The E6 oncogene degrades p53 thereby modulating a large set of p53 target genes as shown previously in the cervical carcinoma cell line HeLa. Here we show that the TAp63beta isoform of the p63 transcription factor is also a target of E6. The p63 gene plays an essential role in skin homeostasis and is expressed as at least six isoforms. One of these isoforms, DeltaNp63alpha, has been found overexpressed in squamous cell carcinomas and is shown here to be constitutively expressed in Caski cells associated with HPV16. We therefore explored the role of p63 in these cells by performing microarray analyses after repression of endogenous E6/E7 expression. Upon repression of the oncogenes, a large set of p53 target genes was found activated together with many p63 target genes related to cell adhesion. However, through siRNA silencing and ectopic expression of various p63 isoforms we demonstrated that TAp63beta is involved in activation of this cell adhesion pathway instead of the constitutively expressed DeltaNp63alpha and beta. Furthermore, we showed in cotransfection experiments, combined with E6AP siRNA silencing, that E6 induces an accelerated degradation of TAp63beta although not through the E6AP ubiquitin ligase used for degradation of p53. Repression of E6 transcription also induces stabilization of endogenous TAp63beta in cervical carcinoma cells that lead to an increased concentration of focal adhesions at the cell surface. Consequently, TAp63beta is the only p63 isoform suppressed by E6 in cervical carcinoma as demonstrated previously for p53. Down-modulation of focal adhesions through disruption of TAp63beta therefore appears as a novel E6-dependent pathway in transformation. These findings identify a major physiological role for TAp63beta in anchorage independent growth that might represent a new critical pathway in human carcinogenesis. PMID- 21980286 TI - Monalysin, a novel beta-pore-forming toxin from the Drosophila pathogen Pseudomonas entomophila, contributes to host intestinal damage and lethality. AB - Pseudomonas entomophila is an entomopathogenic bacterium that infects and kills Drosophila. P. entomophila pathogenicity is linked to its ability to cause irreversible damages to the Drosophila gut, preventing epithelium renewal and repair. Here we report the identification of a novel pore-forming toxin (PFT), Monalysin, which contributes to the virulence of P. entomophila against Drosophila. Our data show that Monalysin requires N-terminal cleavage to become fully active, forms oligomers in vitro, and induces pore-formation in artificial lipid membranes. The prediction of the secondary structure of the membrane spanning domain indicates that Monalysin is a PFT of the beta-type. The expression of Monalysin is regulated by both the GacS/GacA two-component system and the Pvf regulator, two signaling systems that control P. entomophila pathogenicity. In addition, AprA, a metallo-protease secreted by P. entomophila, can induce the rapid cleavage of pro-Monalysin into its active form. Reduced cell death is observed upon infection with a mutant deficient in Monalysin production showing that Monalysin plays a role in P. entomophila ability to induce intestinal cell damages, which is consistent with its activity as a PFT. Our study together with the well-established action of Bacillus thuringiensis Cry toxins suggests that production of PFTs is a common strategy of entomopathogens to disrupt insect gut homeostasis. PMID- 21980287 TI - A novel metal transporter mediating manganese export (MntX) regulates the Mn to Fe intracellular ratio and Neisseria meningitidis virulence. AB - Neisseria meningitidis (Nm) and N. gonorrhoeae (Ng) are adapted to different environments within their human host. If the basis of this difference has not yet been fully understood, previous studies (including our own data) have reported that, unlike Ng, Nm tolerates high manganese concentrations. As transition metals are essential regulators of cell growth and host pathogen interactions, we aimed to address mechanisms of Nm Mn2+ tolerance and its pathogenic consequences. Using bioinformatics, gene deletion and heterologous expression we identified a conserved bacterial manganese resistance factor MntX (formerly YebN). The predicted structure suggests that MntX represents a new family of transporters exporting Mn. In the Neisseria genus, this exporter is present and functional in all Nm isolates but it is mutated in a majority of Ng strains and commonly absent in nonpathogenic species. In Nm, Mn2+ export via MntX regulates the intracellular Mn/Fe ratio and protects against manganese toxicity that is exacerbated in low iron conditions. MntX is also important for N. meningitidis to resist killing by human serum and for survival in mice blood during septicemia. The present work thus points to new clues about Mn homeostasis, its interplay with Fe metabolism and the influence on N. meningitidis physiology and pathogenicity. PMID- 21980288 TI - Evaluating the sensitivity of Mycobacterium tuberculosis to biotin deprivation using regulated gene expression. AB - In the search for new drug targets, we evaluated the biotin synthetic pathway of Mycobacterium tuberculosis (Mtb) and constructed an Mtb mutant lacking the biotin biosynthetic enzyme 7,8-diaminopelargonic acid synthase, BioA. In biotin-free synthetic media, DeltabioA did not produce wild-type levels of biotinylated proteins, and therefore did not grow and lost viability. DeltabioA was also unable to establish infection in mice. Conditionally-regulated knockdown strains of Mtb similarly exhibited impaired bacterial growth and viability in vitro and in mice, irrespective of the timing of transcriptional silencing. Biochemical studies further showed that BioA activity has to be reduced by approximately 99% to prevent growth. These studies thus establish that de novo biotin synthesis is essential for Mtb to establish and maintain a chronic infection in a murine model of TB. Moreover, these studies provide an experimental strategy to systematically rank the in vivo value of potential drug targets in Mtb and other pathogens. PMID- 21980289 TI - Tri6 is a global transcription regulator in the phytopathogen Fusarium graminearum. AB - In F. graminearum, the transcriptional regulator Tri6 is encoded within the trichothecene gene cluster and regulates genes involved in the biosynthesis of the secondary metabolite deoxynivalenol (DON). The Tri6 protein with its Cys2His2 zinc-finger may also conform to the class of global transcription regulators. This class of global transcriptional regulators mediate various environmental cues and generally responds to the demands of cellular metabolism. To address this issue directly, we sought to find gene targets of Tri6 in F. graminearum grown in optimal nutrient conditions. Chromatin immunoprecipitation followed by Illumina sequencing (ChIP-Seq) revealed that in addition to identifying six genes within the trichothecene gene cluster, Tri1, Tri3, Tri6, Tri7, Tri12 and Tri14, the ChIP-Seq also identified 192 additional targets potentially regulated by Tri6. Functional classification revealed that, among the annotated genes, ~40% are associated with cellular metabolism and transport and the rest of the target genes fall into the category of signal transduction and gene expression regulation. ChIP-Seq data also revealed Tri6 has the highest affinity toward its own promoter, suggesting that this gene could be subject to self-regulation. Electro mobility shift assays (EMSA) performed on the promoter of Tri6 with purified Tri6 protein identified a minimum binding motif of GTGA repeats as a consensus sequence. Finally, expression profiling of F. graminearum grown under nitrogen-limiting conditions revealed that 49 out of 198 target genes are differentially regulated by Tri6. The identification of potential new targets together with deciphering novel binding sites for Tri6, casts new light into the role of this transcriptional regulator in the overall growth and development of F. graminearum. PMID- 21980290 TI - Exploiting and subverting Tor signaling in the pathogenesis of fungi, parasites, and viruses. PMID- 21980291 TI - Exhausted CD8 T cells downregulate the IL-18 receptor and become unresponsive to inflammatory cytokines and bacterial co-infections. AB - During many chronic infections virus-specific CD8 T cells succumb to exhaustion as they lose their ability to respond to antigenic activation. Combinations of IL 12, IL-18, and IL-21 have been shown to induce the antigen-independent production of interferon (IFN)-gamma by effector and memory CD8 T cells. In this study we investigated whether exhausted CD8 T cells are sensitive to activation by these cytokines. We show that effector and memory, but not exhausted, CD8 T cells produce IFN-gamma and upregulate CD25 following exposure to certain combinations of IL-12, IL-18, and IL-21. The unresponsiveness of exhausted CD8 T cells is associated with downregulation of the IL-18-receptor-alpha (IL-18Ralpha). Although IL-18Ralpha expression is connected with the ability of memory CD8 T cells to self-renew and efflux rhodamine 123, the IL-18Ralpha(lo) exhausted cells remained capable of secreting this dye. To further evaluate the consequences of IL-18Ralpha downregulation, we tracked the fate of IL-18Ralpha-deficient CD8 T cells in chronically infected mixed bone marrow chimeras and discovered that IL 18Ralpha affects the initial but not later phases of the response. The antigen independent responsiveness of exhausted CD8 T cells was also investigated following co-infection with Listeria monocytogenes, which induces the expression of IL-12 and IL-18. Although IL-18Ralpha(hi) memory cells upregulated CD25 and produced IFN-gamma, the IL-18Ralpha(lo) exhausted cells failed to respond. Collectively, these findings indicate that as exhausted T cells adjust to the chronically infected environment, they lose their susceptibility to antigen independent activation by cytokines, which compromises their ability to detect bacterial co-infections. PMID- 21980292 TI - Strain specific resistance to murine scrapie associated with a naturally occurring human prion protein polymorphism at residue 171. AB - Transmissible spongiform encephalopathies (TSE) or prion diseases are neurodegenerative disorders associated with conversion of normal host prion protein (PrP) to a misfolded, protease-resistant form (PrPres). Genetic variations of prion protein in humans and animals can alter susceptibility to both familial and infectious prion diseases. The N171S PrP polymorphism is found mainly in humans of African descent, but its low incidence has precluded study of its possible influence on prion disease. Similar to previous experiments of others, for laboratory studies we created a transgenic model expressing the mouse PrP homolog, PrP-170S, of human PrP-171S. Since PrP polymorphisms can vary in their effects on different TSE diseases, we tested these mice with four different strains of mouse-adapted scrapie. Whereas 22L and ME7 scrapie strains induced typical clinical disease, neuropathology and accumulation of PrPres in all transgenic mice at 99-128 average days post-inoculation, strains RML and 79A produced clinical disease and PrPres formation in only a small subset of mice at very late times. When mice expressing both PrP-170S and PrP-170N were inoculated with RML scrapie, dominant-negative inhibition of disease did not occur, possibly because interaction of strain RML with PrP-170S was minimal. Surprisingly, in vitro PrP conversion using protein misfolding cyclic amplification (PMCA), did not reproduce the in vivo findings, suggesting that the resistance noted in live mice might be due to factors or conditions not present in vitro. These findings suggest that in vivo conversion of PrP-170S by RML and 79A scrapie strains was slow and inefficient. PrP-170S mice may be an example of the conformational selection model where the structure of some prion strains does not favor interactions with PrP molecules expressing certain polymorphisms. PMID- 21980293 TI - Multidrug resistant 2009 A/H1N1 influenza clinical isolate with a neuraminidase I223R mutation retains its virulence and transmissibility in ferrets. AB - Only two classes of antiviral drugs, neuraminidase inhibitors and adamantanes, are approved for prophylaxis and therapy against influenza virus infections. A major concern is that influenza virus becomes resistant to these antiviral drugs and spreads in the human population. The 2009 pandemic A/H1N1 influenza virus is naturally resistant to adamantanes. Recently a novel neuraminidase I223R mutation was identified in an A/H1N1 virus showing cross-resistance to the neuraminidase inhibitors oseltamivir, zanamivir and peramivir. However, the ability of this virus to cause disease and spread in the human population is unknown. Therefore, this clinical isolate (NL/2631-R223) was compared with a well-characterized reference virus (NL/602). In vitro experiments showed that NL/2631-I223R replicated as well as NL/602 in MDCK cells. In a ferret pathogenesis model, body weight loss was similar in animals inoculated with NL/2631-R223 or NL/602. In addition, pulmonary lesions were similar at day 4 post inoculation. However, at day 7 post inoculation, NL/2631-R223 caused milder pulmonary lesions and degree of alveolitis than NL/602. This indicated that the mutant virus was less pathogenic. Both NL/2631-R223 and a recombinant virus with a single I223R change (recNL/602-I223R), transmitted among ferrets by aerosols, despite observed attenuation of recNL/602-I223R in vitro. In conclusion, the I223R mutated virus isolate has comparable replicative ability and transmissibility, but lower pathogenicity than the reference virus based on these in vivo studies. This implies that the 2009 pandemic influenza A/H1N1 virus subtype with an isoleucine to arginine change at position 223 in the neuraminidase has the potential to spread in the human population. It is important to be vigilant for this mutation in influenza surveillance and to continue efforts to increase the arsenal of antiviral drugs to combat influenza. PMID- 21980294 TI - Structure of herpes simplex virus glycoprotein D bound to the human receptor nectin-1. AB - Binding of herpes simplex virus (HSV) glycoprotein D (gD) to a cell surface receptor is required to trigger membrane fusion during entry into host cells. Nectin-1 is a cell adhesion molecule and the main HSV receptor in neurons and epithelial cells. We report the structure of gD bound to nectin-1 determined by x ray crystallography to 4.0 A resolution. The structure reveals that the nectin-1 binding site on gD differs from the binding site of the HVEM receptor. A surface on the first Ig-domain of nectin-1, which mediates homophilic interactions of Ig like cell adhesion molecules, buries an area composed by residues from both the gD N- and C-terminal extensions. Phenylalanine 129, at the tip of the loop connecting beta-strands F and G of nectin-1, protrudes into a groove on gD, which is otherwise occupied by C-terminal residues in the unliganded gD and by N terminal residues in the gD/HVEM complex. Notably, mutation of Phe129 to alanine prevents nectin-1 binding to gD and HSV entry. Together these data are consistent with previous studies showing that gD disrupts the normal nectin-1 homophilic interactions. Furthermore, the structure of the complex supports a model in which gD-receptor binding triggers HSV entry through receptor-mediated displacement of the gD C-terminal region. PMID- 21980295 TI - Rapid and efficient clearance of blood-borne virus by liver sinusoidal endothelium. AB - The liver removes quickly the great bulk of virus circulating in blood, leaving only a small fraction to infect the host, in a manner characteristic of each virus. The scavenger cells of the liver sinusoids are implicated, but the mechanism is entirely unknown. Here we show, borrowing a mouse model of adenovirus clearance, that nearly all infused adenovirus is cleared by the liver sinusoidal endothelial cell (LSEC). Using refined immunofluorescence microscopy techniques for distinguishing macrophages and endothelial cells in fixed liver, and identifying virus by two distinct physicochemical methods, we localized adenovirus 1 minute after infusion mainly to the LSEC (~90%), finding ~10% with Kupffer cells (KC) and none with hepatocytes. Electron microscopy confirmed our results. In contrast with much prior work claiming the main scavenger to be the KC, our results locate the clearance mechanism to the LSEC and identify this cell as a key site of antiviral activity. PMID- 21980297 TI - Bmp and nodal independently regulate lefty1 expression to maintain unilateral nodal activity during left-right axis specification in zebrafish. AB - In vertebrates, left-right (LR) axis specification is determined by a ciliated structure in the posterior region of the embryo. Fluid flow in this ciliated structure is responsible for the induction of unilateral left-sided Nodal activity in the lateral plate mesoderm, which in turn regulates organ laterality. Bmp signalling activity has been implied in repressing Nodal expression on the right side, however its mechanism of action has been controversial. In a forward genetic screen for mutations that affect LR patterning, we identified the zebrafish linkspoot (lin) mutant, characterized by cardiac laterality and mild dorsoventral patterning defects. Mapping of the lin mutation revealed an inactivating missense mutation in the Bmp receptor 1aa (bmpr1aa) gene. Embryos with a mutation in lin/bmpr1aa and a novel mutation in its paralogue, bmpr1ab, displayed a variety of dorsoventral and LR patterning defects with increasing severity corresponding with a decrease in bmpr1a dosage. In Bmpr1a-deficient embryos we observed bilateral expression of the Nodal-related gene, spaw, coupled with reduced expression of the Nodal-antagonist lefty1 in the midline. Using genetic models to induce or repress Bmp activity in combination with Nodal inhibition or activation, we found that Bmp and Nodal regulate lefty1 expression in the midline independently of each other. Furthermore, we observed that the regulation of lefty1 by Bmp signalling is required for its observed downregulation of Nodal activity in the LPM providing a novel explanation for this phenomenon. From these results we propose a two-step model in which Bmp regulates LR patterning. Prior to the onset of nodal flow and Nodal activation, Bmp is required to induce lefty1 expression in the midline. When nodal flow has been established and Nodal activity is apparent, both Nodal and Bmp independently are required for lefty1 expression to assure unilateral Nodal activation and correct LR patterning. PMID- 21980298 TI - Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD. AB - Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR <60ml/min/1.73m(2) at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression. PMID- 21980299 TI - A genome-wide meta-analysis of six type 1 diabetes cohorts identifies multiple associated loci. AB - Diabetes impacts approximately 200 million people worldwide, of whom approximately 10% are affected by type 1 diabetes (T1D). The application of genome-wide association studies (GWAS) has robustly revealed dozens of genetic contributors to the pathogenesis of T1D, with the most recent meta-analysis identifying in excess of 40 loci. To identify additional genetic loci for T1D susceptibility, we examined associations in the largest meta-analysis to date between the disease and ~2.54 million SNPs in a combined cohort of 9,934 cases and 16,956 controls. Targeted follow-up of 53 SNPs in 1,120 affected trios uncovered three new loci associated with T1D that reached genome-wide significance. The most significantly associated SNP (rs539514, P = 5.66*10-11) resides in an intronic region of the LMO7 (LIM domain only 7) gene on 13q22. The second most significantly associated SNP (rs478222, P = 3.50*10-9 resides in an intronic region of the EFR3B (protein EFR3 homolog B) gene on 2p23; however, the region of linkage disequilibrium is approximately 800 kb and harbors additional multiple genes, including NCOA1, C2orf79, CENPO, ADCY3, DNAJC27, POMC, and DNMT3A. The third most significantly associated SNP (rs924043, P = 8.06*10-9 lies in an intergenic region on 6q27, where the region of association is approximately 900 kb and harbors multiple genes including WDR27, C6orf120, PHF10, TCTE3, C6orf208, LOC154449, DLL1, FAM120B, PSMB1, TBP, and PCD2. These latest associated regions add to the growing repertoire of gene networks predisposing to T1D. PMID- 21980300 TI - Genomic analysis of QTLs and genes altering natural variation in stochastic noise. AB - Quantitative genetic analysis has long been used to study how natural variation of genotype can influence an organism's phenotype. While most studies have focused on genetic determinants of phenotypic average, it is rapidly becoming understood that stochastic noise is genetically determined. However, it is not known how many traits display genetic control of stochastic noise nor how broadly these stochastic loci are distributed within the genome. Understanding these questions is critical to our understanding of quantitative traits and how they relate to the underlying causal loci, especially since stochastic noise may be directly influenced by underlying changes in the wiring of regulatory networks. We identified QTLs controlling natural variation in stochastic noise of glucosinolates, plant defense metabolites, as well as QTLs for stochastic noise of related transcripts. These loci included stochastic noise QTLs unique for either transcript or metabolite variation. Validation of these loci showed that genetic polymorphism within the regulatory network alters stochastic noise independent of effects on corresponding average levels. We examined this phenomenon more globally, using transcriptomic datasets, and found that the Arabidopsis transcriptome exhibits significant, heritable differences in stochastic noise. Further analysis allowed us to identify QTLs that control genomic stochastic noise. Some genomic QTL were in common with those altering average transcript abundance, while others were unique to stochastic noise. Using a single isogenic population, we confirmed that natural variation at ELF3 alters stochastic noise in the circadian clock and metabolism. Since polymorphisms controlling stochastic noise in genomic phenotypes exist within wild germplasm for naturally selected phenotypes, this suggests that analysis of Arabidopsis evolution should account for genetic control of stochastic variance and average phenotypes. It remains to be determined if natural genetic variation controlling stochasticity is equally distributed across the genomes of other multi-cellular eukaryotes. PMID- 21980301 TI - Inter-allelic prion propagation reveals conformational relationships among a multitude of [PSI] strains. AB - Immense diversity of prion strains is observed, but its underlying mechanism is less clear. Three [PSI] prion strains--named VH, VK, and VL--were previously isolated in the wild-type yeast genetic background. Here we report the generation and characterization of eight new [PSI] isolates, obtained by propagating the wild-type strains with Sup35 proteins containing single amino-acid alterations. The VH strain splits into two distinct strains when propagated in each of the three genetic backgrounds, harboring respectively single mutations of N21L, R28P, and Gi47 (i.e. insertion of a glycine residue at position 47) on the Sup35 N terminal prion-forming segment. The six new strains exhibit complex inter conversion patterns, and one of them continuously mutates into another. However, when they are introduced back into the wild-type background, all 6 strains revert to the VH strain. We obtain two more [PSI] isolates by propagating VK and VL with the Gi47 and N21L backgrounds, respectively. The two isolates do not transmit to other mutant backgrounds but revert to their parental strains in the wild-type background. Our data indicate that a large number of [PSI] strains can be built on three basic Sup35 amyloid structures. It is proposed that the three basic structures differ by chain folding topologies, and sub-strains with the same topology differ in distinct ways by local structural adjustments. This "large number of variations on a small number of basic themes" may also be operative in generating strain diversities in other prion elements. It thus suggests a possible general scheme to classify a multitude of prion strains. PMID- 21980302 TI - A conserved PHD finger protein and endogenous RNAi modulate insulin signaling in Caenorhabditis elegans. AB - Insulin signaling has a profound effect on longevity and the oxidative stress resistance of animals. Inhibition of insulin signaling results in the activation of DAF-16/FOXO and SKN-1/Nrf transcription factors and increased animal fitness. By studying the biological functions of the endogenous RNA interference factor RDE-4 and conserved PHD zinc finger protein ZFP-1 (AF10), which regulate overlapping sets of genes in Caenorhabditis elegans, we identified an important role for these factors in the negative modulation of transcription of the insulin/PI3 signaling-dependent kinase PDK-1. Consistently, increased expression of pdk-1 in zfp-1 and rde-4 mutants contributed to their reduced lifespan and sensitivity to oxidative stress and pathogens due to the reduction in the expression of DAF-16 and SKN-1 targets. We found that the function of ZFP-1 in modulating pdk-1 transcription was important for the extended lifespan of the age 1(hx546) reduction-of-function PI3 kinase mutant, since the lifespan of the age 1; zfp-1 double mutant strain was significantly shorter compared to age-1(hx546). We further demonstrate that overexpression of ZFP-1 caused an increased resistance to oxidative stress in a DAF-16-dependent manner. Our findings suggest that epigenetic regulation of key upstream signaling components in signal transduction pathways through chromatin and RNAi may have a large impact on the outcome of signaling and expression of numerous downstream genes. PMID- 21980303 TI - Identification of type 1 diabetes-associated DNA methylation variable positions that precede disease diagnosis. AB - Monozygotic (MZ) twin pair discordance for childhood-onset Type 1 Diabetes (T1D) is ~50%, implicating roles for genetic and non-genetic factors in the aetiology of this complex autoimmune disease. Although significant progress has been made in elucidating the genetics of T1D in recent years, the non-genetic component has remained poorly defined. We hypothesized that epigenetic variation could underlie some of the non-genetic component of T1D aetiology and, thus, performed an epigenome-wide association study (EWAS) for this disease. We generated genome wide DNA methylation profiles of purified CD14+ monocytes (an immune effector cell type relevant to T1D pathogenesis) from 15 T1D-discordant MZ twin pairs. This identified 132 different CpG sites at which the direction of the intra-MZ pair DNA methylation difference significantly correlated with the diabetic state, i.e. T1D-associated methylation variable positions (T1D-MVPs). We confirmed these T1D-MVPs display statistically significant intra-MZ pair DNA methylation differences in the expected direction in an independent set of T1D-discordant MZ pairs (P = 0.035). Then, to establish the temporal origins of the T1D-MVPs, we generated two further genome-wide datasets and established that, when compared with controls, T1D-MVPs are enriched in singletons both before (P = 0.001) and at (P = 0.015) disease diagnosis, and also in singletons positive for diabetes associated autoantibodies but disease-free even after 12 years follow-up (P = 0.0023). Combined, these results suggest that T1D-MVPs arise very early in the etiological process that leads to overt T1D. Our EWAS of T1D represents an important contribution toward understanding the etiological role of epigenetic variation in type 1 diabetes, and it is also the first systematic analysis of the temporal origins of disease-associated epigenetic variation for any human complex disease. PMID- 21980304 TI - Retrotransposon-induced heterochromatin spreading in the mouse revealed by insertional polymorphisms. AB - The "arms race" relationship between transposable elements (TEs) and their host has promoted a series of epigenetic silencing mechanisms directed against TEs. Retrotransposons, a class of TEs, are often located in repressed regions and are thought to induce heterochromatin formation and spreading. However, direct evidence for TE-induced local heterochromatin in mammals is surprisingly scarce. To examine this phenomenon, we chose two mouse embryonic stem (ES) cell lines that possess insertionally polymorphic retrotransposons (IAP, ETn/MusD, and LINE elements) at specific loci in one cell line but not the other. Employing ChIP-seq data for these cell lines, we show that IAP elements robustly induce H3K9me3 and H4K20me3 marks in flanking genomic DNA. In contrast, such heterochromatin is not induced by LINE copies and only by a minority of polymorphic ETn/MusD copies. DNA methylation is independent of the presence of IAP copies, since it is present in flanking regions of both full and empty sites. Finally, such spreading into genes appears to be rare, since the transcriptional start sites of very few genes are less than one Kb from an IAP. However, the B3galtl gene is subject to transcriptional silencing via IAP-induced heterochromatin. Hence, although rare, IAP-induced local heterochromatin spreading into nearby genes may influence expression and, in turn, host fitness. PMID- 21980305 TI - Misregulation of Scm3p/HJURP causes chromosome instability in Saccharomyces cerevisiae and human cells. AB - The kinetochore (centromeric DNA and associated proteins) is a key determinant for high fidelity chromosome transmission. Evolutionarily conserved Scm3p is an essential component of centromeric chromatin and is required for assembly and function of kinetochores in humans, fission yeast, and budding yeast. Overexpression of HJURP, the mammalian homolog of budding yeast Scm3p, has been observed in lung and breast cancers and is associated with poor prognosis; however, the physiological relevance of these observations is not well understood. We overexpressed SCM3 and HJURP in Saccharomyces cerevisiae and HJURP in human cells and defined domains within Scm3p that mediate its chromosome loss phenotype. Our results showed that the overexpression of SCM3 (GALSCM3) or HJURP (GALHJURP) caused chromosome loss in a wild-type yeast strain, and overexpression of HJURP led to mitotic defects in human cells. GALSCM3 resulted in reduced viability in kinetochore mutants, premature separation of sister chromatids, and reduction in Cse4p and histone H4 at centromeres. Overexpression of CSE4 or histone H4 suppressed chromosome loss and restored levels of Cse4p at centromeres in GALSCM3 strains. Using mutant alleles of scm3, we identified a domain in the N terminus of Scm3p that mediates its interaction with CEN DNA and determined that the chromosome loss phenotype of GALSCM3 is due to centromeric association of Scm3p devoid of Cse4p/H4. Furthermore, we determined that similar to other systems the centromeric association of Scm3p is cell cycle regulated. Our results show that altered stoichiometry of Scm3p/HJURP, Cse4p, and histone H4 lead to defects in chromosome segregation. We conclude that stringent regulation of HJURP and SCM3 expression are critical for genome stability. PMID- 21980306 TI - Genome-wide analysis of heteroduplex DNA in mismatch repair-deficient yeast cells reveals novel properties of meiotic recombination pathways. AB - Meiotic DNA double-strand breaks (DSBs) initiate crossover (CO) recombination, which is necessary for accurate chromosome segregation, but DSBs may also repair as non-crossovers (NCOs). Multiple recombination pathways with specific intermediates are expected to lead to COs and NCOs. We revisited the mechanisms of meiotic DSB repair and the regulation of CO formation, by conducting a genome wide analysis of strand-transfer intermediates associated with recombination events. We performed this analysis in a SK1 * S288C Saccharomyces cerevisiae hybrid lacking the mismatch repair (MMR) protein Msh2, to allow efficient detection of heteroduplex DNAs (hDNAs). First, we observed that the anti recombinogenic activity of MMR is responsible for a 20% drop in CO number, suggesting that in MMR-proficient cells some DSBs are repaired using the sister chromatid as a template when polymorphisms are present. Second, we observed that a large fraction of NCOs were associated with trans-hDNA tracts constrained to a single chromatid. This unexpected finding is compatible with dissolution of double Holliday junctions (dHJs) during repair, and it suggests the existence of a novel control point for CO formation at the level of the dHJ intermediate, in addition to the previously described control point before the dHJ formation step. Finally, we observed that COs are associated with complex hDNA patterns, confirming that the canonical double-strand break repair model is not sufficient to explain the formation of most COs. We propose that multiple factors contribute to the complexity of recombination intermediates. These factors include repair of nicks and double-stranded gaps, template switches between non-sister and sister chromatids, and HJ branch migration. Finally, the good correlation between the strand transfer properties observed in the absence of and in the presence of Msh2 suggests that the intermediates detected in the absence of Msh2 reflect normal intermediates. PMID- 21980307 TI - MicroRNA predictors of longevity in Caenorhabditis elegans. AB - Neither genetic nor environmental factors fully account for variability in individual longevity: genetically identical invertebrates in homogenous environments often experience no less variability in lifespan than outbred human populations. Such variability is often assumed to result from stochasticity in damage accumulation over time; however, the identification of early-life gene expression states that predict future longevity would suggest that lifespan is least in part epigenetically determined. Such "biomarkers of aging," genetic or otherwise, nevertheless remain rare. In this work, we sought early-life differences in organismal robustness in unperturbed individuals and examined the utility of microRNAs, known regulators of lifespan, development, and robustness, as aging biomarkers. We quantitatively examined Caenorhabditis elegans reared individually in a novel apparatus and observed throughout their lives. Early-to mid-adulthood measures of homeostatic ability jointly predict 62% of longevity variability. Though correlated, markers of growth/muscle maintenance and of metabolic by-products ("age pigments") report independently on lifespan, suggesting that graceful aging is not a single process. We further identified three microRNAs in which early-adulthood expression patterns individually predict up to 47% of lifespan differences. Though expression of each increases throughout this time, mir-71 and mir-246 correlate with lifespan, while mir-239 anti correlates. Two of these three microRNA "biomarkers of aging" act upstream in insulin/IGF-1-like signaling (IIS) and other known longevity pathways, thus we infer that these microRNAs not only report on but also likely determine longevity. Thus, fluctuations in early-life IIS, due to variation in these microRNAs and from other causes, may determine individual lifespan. PMID- 21980308 TI - A noncoding point mutation of Zeb1 causes multiple developmental malformations and obesity in Twirler mice. AB - Heterozygous Twirler (Tw) mice develop obesity and circling behavior associated with malformations of the inner ear, whereas homozygous Tw mice have cleft palate and die shortly after birth. Zeb1 is a zinc finger protein that contributes to mesenchymal cell fate by repression of genes whose expression defines epithelial cell identity. This developmental pathway is disrupted in inner ears of Tw/Tw mice. The purpose of our study was to comprehensively characterize the Twirler phenotype and to identify the causative mutation. The Tw/+ inner ear phenotype includes irregularities of the semicircular canals, abnormal utricular otoconia, a shortened cochlear duct, and hearing loss, whereas Tw/Tw ears are severely malformed with barely recognizable anatomy. Tw/+ mice have obesity associated with insulin-resistance and have lymphoid organ hypoplasia. We identified a noncoding nucleotide substitution, c.58+181G>A, in the first intron of the Tw allele of Zeb1 (Zeb1(Tw)). A knockin mouse model of c.58+181G>A recapitulated the Tw phenotype, whereas a wild-type knockin control did not, confirming the mutation as pathogenic. c.58+181G>A does not affect splicing but disrupts a predicted site for Myb protein binding, which we confirmed in vitro. In comparison, homozygosity for a targeted deletion of exon 1 of mouse Zeb1, Zeb1(DeltaEx1), is associated with a subtle abnormality of the lateral semicircular canal that is different than those in Tw mice. Expression analyses of E13.5 Twirler and Zeb1(DeltaEx1) ears confirm that Zeb1(DeltaEx1) is a null allele, whereas Zeb1(Tw) RNA is expressed at increased levels in comparison to wild-type Zeb1. We conclude that a noncoding point mutation of Zeb1 acts via a gain-of-function to disrupt regulation of Zeb1(Tw) expression, epithelial mesenchymal cell fate or interactions, and structural development of the inner ear in Twirler mice. This is a novel mechanism underlying disorders of hearing or balance. PMID- 21980309 TI - Cell type-specific transcriptome analysis reveals a major role for Zeb1 and miR 200b in mouse inner ear morphogenesis. AB - Cellular heterogeneity hinders the extraction of functionally significant results and inference of regulatory networks from wide-scale expression profiles of complex mammalian organs. The mammalian inner ear consists of the auditory and vestibular systems that are each composed of hair cells, supporting cells, neurons, mesenchymal cells, other epithelial cells, and blood vessels. We developed a novel protocol to sort auditory and vestibular tissues of newborn mouse inner ears into their major cellular components. Transcriptome profiling of the sorted cells identified cell type-specific expression clusters. Computational analysis detected transcription factors and microRNAs that play key roles in determining cell identity in the inner ear. Specifically, our analysis revealed the role of the Zeb1/miR-200b pathway in establishing epithelial and mesenchymal identity in the inner ear. Furthermore, we detected a misregulation of the ZEB1 pathway in the inner ear of Twirler mice, which manifest, among other phenotypes, malformations of the auditory and vestibular labyrinth. The association of misregulation of the ZEB1/miR-200b pathway with auditory and vestibular defects in the Twirler mutant mice uncovers a novel mechanism underlying deafness and balance disorders. Our approach can be employed to decipher additional complex regulatory networks underlying other hearing and balance mouse mutants. PMID- 21980310 TI - NOTCH Signaling and ATOH1 in Colorectal Cancers. AB - The Notch receptor signaling pathway regulates expression of the basic helix-loop helix transcription factor ATOH1 (Math1/Hath1) to determine cell fate in the intestine. In differentiating intestinal stem cells, high levels of Notch activity specify absorptive enterocyte/colonocyte differentiation, whereas high ATOH1 activity specifies secretory (goblet, enteroendocrine, and Paneth) cell differentiation. In colorectal cancer, ATOH1 is a tumor suppressor that is silenced in most tumors, while Notch is oncogenic and often highly active in human tumors. In other gastrointestinal malignancies with features of intestinal metaplasia, such as esophageal and gastric cancers, the Notch-ATOH1 pathway becomes activated. In cancers and preneoplastic tissues that retain the ability to activate ATOH1, therapeutic targeting of this pathway can be achieved by inhibiting Notch activity (with Notch-targeting antibodies or small-molecule inhibitors of gamma-secretase). Thus, targeting the Notch-ATOH1 pathway represents a novel approach to differentiation therapy in gastrointestinal cancers. PMID- 21980311 TI - Signals and circuits in the purkinje neuron. AB - Purkinje neurons (PN) in the cerebellum have over 100,000 inputs organized in an orthogonal geometry, and a single output channel. As the sole output of the cerebellar cortex layer, their complex firing pattern has been associated with motor control and learning. As such they have been extensively modeled and measured using tools ranging from electrophysiology and neuroanatomy, to dynamic systems and artificial intelligence methods. However, there is an alternative approach to analyze and describe the neuronal output of these cells using concepts from electrical engineering, particularly signal processing and digital/analog circuits. By viewing the PN as an unknown circuit to be reverse engineered, we can use the tools that provide the foundations of today's integrated circuits and communication systems to analyze the Purkinje system at the circuit level. We use Fourier transforms to analyze and isolate the inherent frequency modes in the PN and define three unique frequency ranges associated with the cells' output. Comparing the PN to a signal generator that can be externally modulated adds an entire level of complexity to the functional role of these neurons both in terms of data analysis and information processing, relying on Fourier analysis methods in place of statistical ones. We also re-describe some of the recent literature in the field, using the nomenclature of signal processing. Furthermore, by comparing the experimental data of the past decade with basic electronic circuitry, we can resolve the outstanding controversy in the field, by recognizing that the PN can act as a multivibrator circuit. PMID- 21980312 TI - Amygdaloid-striatal substrates underlying odor hedonics and odor-guided behaviors. PMID- 21980314 TI - An assessment of behavioral dynamic information processing measures in audiovisual speech perception. AB - Research has shown that visual speech perception can assist accuracy in identification of spoken words. However, little is known about the dynamics of the processing mechanisms involved in audiovisual integration. In particular, architecture and capacity, measured using response time methodologies, have not been investigated. An issue related to architecture concerns whether the auditory and visual sources of the speech signal are integrated "early" or "late." We propose that "early" integration most naturally corresponds to coactive processing whereas "late" integration corresponds to separate decisions parallel processing. We implemented the double factorial paradigm in two studies. First, we carried out a pilot study using a two-alternative forced-choice discrimination task to assess architecture, decision rule, and provide a preliminary assessment of capacity (integration efficiency). Next, Experiment 1 was designed to specifically assess audiovisual integration efficiency in an ecologically valid way by including lower auditory S/N ratios and a larger response set size. Results from the pilot study support a separate decisions parallel, late integration model. Results from both studies showed that capacity was severely limited for high auditory signal-to-noise ratios. However, Experiment 1 demonstrated that capacity improved as the auditory signal became more degraded. This evidence strongly suggests that integration efficiency is vitally affected by the S/N ratio. PMID- 21980313 TI - Non-invasive brain stimulation enhances the effects of melodic intonation therapy. AB - Research has suggested that a fronto-temporal network in the right hemisphere may be responsible for mediating melodic intonation therapy's (MIT) positive effects on speech recovery. We investigated the potential for a non-invasive brain stimulation technique, transcranial direct current stimulation (tDCS), to augment the benefits of MIT in patients with non-fluent aphasia by modulating neural activity in the brain during treatment with MIT. The polarity of the current applied to the scalp determines the effects of tDCS on the underlying tissue: anodal-tDCS increases excitability, whereas cathodal tDCS decreases excitability. We applied anodal-tDCS to the posterior inferior frontal gyrus of the right hemisphere, an area that has been shown both to contribute to singing through the mapping of sounds to articulatory actions and to serve as a key region in the process of recovery from aphasia, particularly in patients with large left hemisphere lesions. The stimulation was applied while patients were treated with MIT by a trained therapist. Six patients with moderate to severe non-fluent aphasia underwent three consecutive days of anodal-tDCS + MIT, and an equivalent series of sham-tDCS + MIT. The two treatment series were separated by 1 week, and the order in which the treatments were administered was randomized. Compared to the effects of sham-tDCS + MIT, anodal-tDCS + MIT led to significant improvements in fluency of speech. These results support the hypothesis that, as the brain seeks to reorganize and compensate for damage to left hemisphere language centers, combining anodal-tDCS with MIT may further recovery from post-stroke aphasia by enhancing activity in a right hemisphere sensorimotor network for articulation. PMID- 21980315 TI - Is Finger-counting Necessary for the Development of Arithmetic Abilities? PMID- 21980316 TI - Monetary incentives in speeded perceptual decision: effects of penalizing errors versus slow responses. AB - The influence of monetary incentives on performance has been widely investigated among various disciplines. While the results reveal positive incentive effects only under specific conditions, the exact nature, and the contribution of mediating factors are largely unexplored. The present study examined influences of payoff schemes as one of these factors. In particular, we manipulated penalties for errors and slow responses in a speeded categorization task. The data show improved performance for monetary over symbolic incentives when (a) penalties are higher for slow responses than for errors, and (b) neither slow responses nor errors are punished. Conversely, payoff schemes with stronger punishment for errors than for slow responses resulted in worse performance under monetary incentives. The findings suggest that an emphasis of speed is favorable for positive influences of monetary incentives, whereas an emphasis of accuracy under time pressure has the opposite effect. PMID- 21980317 TI - Immunity and AAV-Mediated Gene Therapy for Muscular Dystrophies in Large Animal Models and Human Trials. AB - Adeno-associated viral (AAV) vector-mediated gene replacement for the treatment of muscular dystrophy represents a promising therapeutic strategy in modern medicine. One major obstacle in using AAV vectors for in vivo gene delivery is the development of host immune responses to the viral capsid protein and transgene products as evidenced in animal models and human trials for a range of genetic diseases. Here, we review immunity against AAV vector and transgene in the context of gene delivery specific to muscles for treating muscular dystrophies and non-muscle diseases in large animal models and human trials, factors that influence the intensity of the immune responses, and immune modulatory strategies to prevent unwanted immune responses and induce tolerance to the vector and therapeutic gene for a successful gene therapy. PMID- 21980318 TI - Theoretical Analysis of Shear Wave Interference Patterns by Means of Dynamic Acoustic Radiation Forces. AB - Acoustic radiation forces associated with high intensity focused ultrasound stimulate shear wave propagation allowing shear wave speed and shear viscosity estimation of tissue structures. As wave speeds are meters per second, real time displacement tracking over an extend field-of-view using ultrasound is problematic due to very high frame rate requirements. However, two spatially separated dynamic external sources can stimulate shear wave motion leading to shear wave interference patterns. Advantages are shear waves can be imaged at lower frame rates and local interference pattern spatial properties reflect tissue's viscoelastic properties. Here a theoretical analysis of shear wave interference patterns by means of dynamic acoustic radiation forces is detailed. Using a viscoelastic Green's function analysis, tissue motion due to a pair of focused ultrasound beams and associated radiation forces are presented. Overall, this paper theoretically demonstrates shear wave interference patterns can be stimulated using dynamic acoustic radiation forces and tracked using conventional ultrasound imaging. PMID- 21980320 TI - Effects of ovariectomy and ascorbic acid supplement on oxidative stress parameters and bone mineral density in rats. AB - OBJECTIVES: The aim of this study is to investigate the effects of ovariectomy on bone mineral density (BMD) and oxidative state in rats, and the alterations in these effects that vitamin C supplementation may produce. MATERIALS AND METHODS: TWENTY FEMALE WISTAR ALBINO RATS WERE RANDOMLY DIVIDED INTO THREE GROUPS: control (C, n=6); ovariectomy (O, n=7); and ovariectomy+vitamin C supplement (OV, n=7). Oxidative stress (OS) was assessed 100 days postovariectomy by measuring the activity of several enzymes, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase, as well as the concentrations of malondialdehyde (MDA), nitric oxide (NO), and total sulfhydryl groups in plasma and bone homogenates. RESULTS: A significant decrease in BMD was observed in O group compared with C group (p=0.015), and a significant increase was observed in OV compared with O group (p=0.003). When groups were compared with respect to parameters of OS, MDA and NO levels in bone tissue were significantly higher in O than in C (p=0.032, p=0.022) and were significantly lower in OV than in O (p=0.025, p=0.018). SOD activity was significantly higher in O than in C (p=0.032). In plasma, MDA activity was significantly higher in O than in C (p=0.022) and NO level was significantly higher in O than in C and OV (p=0.017, p=0.018). CONCLUSIONS: Our results suggest that ovariectomy may produce osteoporosis and OS in females, and vitamin C supplementation may provide alterations regarding improvement in OS and BMD values. We assume that studies including more subjects are needed to make a decisive conclusion about OS-BMD relation. PMID- 21980321 TI - Synchronous lung cancers: when same histological types feature different molecular profiles and response phenotypes. AB - We discuss the case of synchronous bilateral lung cancers which feature the same histological phenotype and a different EGFR mutational profile. Both histological and molecular characterizations were performed on specimens derived thorough CT guided fine needle aspiration. A first-line chemotherapy was unsuccessful. Subsequent objective response to the EGFR inhibitor Erlotinib was clearly coherent with the sequencing data and the mutated nodule was effectively reduced (> 50%) after therapy, while the lesion assessed as EGFR wild type featured a slight response. This report has two relevant implications. It points out that in case of multiple malignant lesions at time of diagnosis, molecular profiling should be as extensive as possible and it might contribute to clarify the association between the lesions found. Besides the molecular analysis on cytology specimens could identify an accurate and safe diagnostic approach for clinical use. PMID- 21980319 TI - Innovative clinical trial design for pediatric therapeutics. AB - Until approximately 15 years ago, sponsors rarely included children in the development of therapeutics. US and European legislation has resulted in an increase in the number of pediatric trials and specific label changes and dosing recommendations, although infants remain an understudied group. The lack of clinical trials in children is partly due to specific challenges in conducting trials in this patient population. Therapeutics in special populations, including premature infants, obese children and children receiving extracorporeal life support, are even less studied. National research networks in Europe and the USA are beginning to address some of the gaps in pediatric therapeutics using novel clinical trial designs. Recent innovations in pediatric clinical trial design, including sparse and scavenged sampling, population pharmacokinetic analyses and 'opportunistic' studies, have addressed some of the historical challenges associated with clinical trials in children. PMID- 21980322 TI - The First Type III Domain of Fibronectin is Associated with the Expression of Cytokines within the Lung Tumor Microenvironment. AB - Recent studies have pointed to changes in tissue mechanics as a contributory element to the development of malignancies. Increased tissue rigidity is associated with the unfolding of the Type III domains of fibronectin within the extracellular matrix. The consequences of this unfolding on cellular functions within the lung are not well understood. In the present study, we evaluated the effect of a peptide representing a partially unfolded intermediate of the first Type III repeat of fibronectin (FnIII-1c) on inflammatory gene expression in adult human lung fibroblast cells. FnIII-1c induced expression of cytokines, CXCL1-3, IL-8 and TNF-alpha, by lung fibroblast cells. The increase in IL-8 expression was dependent on Toll-like receptor 2 and NFkappaB. Immunohistochemistry of tissue arrays representing squamous cell carcinoma of the lung revealed extensive stromal staining for IL-8 and fibronectin fibrils which were co-aligned with myofibroblasts. These data suggest a model in which unfolding of FnIII domains secondary to myofibroblast-generated tension may induce the release of cytokines by stromal fibroblasts present within the lung tumor. PMID- 21980323 TI - Metastatic signet ring cell carcinoma of the bilateral breasts and ovaries from gastrointestinal tract in a young breastfeeding female - a case report. AB - We report a case of a metastatic signet ring cell carcinoma (SRCC) of gastrointestinal tract. The case is very rare because gastrointestinal tract SRCC was metastatic to bilateral breasts and ovaries (Krukenberg tumor) in the same young woman almost synchronously under breastfeeding condition. Though the primary site was not detected, IHC results fully verified that the tumor originated from gastrointestinal tract. The severe situation of the patient was believed to be connected to her high estrogen hormone. PMID- 21980324 TI - miRNA Alterations Modify Kinase Activation In The IGF-1 Pathway And Correlate With Colorectal Cancer Stage And Progression In Patients. AB - Investigation of therapy naive human tumor and adjacent normal tissue biopsies demonstrated that expression levels of miRNAs are altered at and between stages of CRC. Targets of these altered miRNAs are members of the Insulin signaling pathways. Phosphorylation states of several molecules in the Insulin signaling pathways were altered between stages of CRC, and significantly the change in molecular phosphorylation state correlated with decreases in specific miRNAs that target them. This data establishes a direct relationship between decreased expression of specific miRNAs and increased phosphorylation events in the IGF-1 pathway and identifies the IGF-1 pathway as a critical driver of colorectal cancer.The expression levels of 319 miRNAs and phosphorylation levels of major signaling proteins were determined. Interestingly, we observed that miRNAs were altered in expression and several signaling molecules were altered in phosphorylation levels at and between each stage of CRC. Furthermore, many of the miRNAs that are differentially expressed at each CRC stage were targeting these same signaling proteins identified to be altered in phosphorylation level. Thus, our studies define a subset of important miRNAs to classify CRC stage and a relationship between miRNA depression and elevated phosphorylation of IGF-1R pathway signaling molecules. PMID- 21980325 TI - Cavitary lung cancer lined with normal bronchial epithelium and cancer cells. AB - Reports of cavitary lung cancer are not uncommon, and the cavity generally contains either dilated bronchi or cancer cells. Recently, we encountered a surgical case of cavitary lung cancer whose cavity tended to enlarge during long term follow-up, and was found to be lined with normal bronchial epithelium and adenocarcinoma cells. PMID- 21980326 TI - Effect of Geometry on the Leaflet Stresses in Simulated Models of Congenital Bicuspid Aortic Valves. AB - The aim of the study was to assess the effect of geometric variations on the stresses developed in the leaflets of congenital bicuspid aortic valves (CBAV). We developed a model for the human tri-leaflet aortic valve based on the geometry and dimensions published in the literature. We also developed simulated CBAV geometry based on the most common geometry present in patients with CBAV that is published in the literature. We employed a constitutive relationship for the leaflet material from the previously published experimental data of fresh porcine aortic valve leaflet specimens for the analysis. We performed dynamic finite element (FE) structural analysis of the valves in the aortic position in order to compute the strain and stress distribution on the leaflets of the tri-leaflet valve and the CBAV models. Our results showed that large changes in the computed in-plane leaflet strain and stress occurred with variations in the geometry of the simulated CBAV whereas changes due to alterations in material constants were correspondingly less. The valve orifice area in the fully open position was significantly reduced in CBAV compared to that for the tri-leaflet valve. The changes in geometry of CBAV resulted in large changes in in-plane strain and stress and our results suggest that geometrical variations may be a potential risk factor inducing calcific aortic stenosis frequently present in patients with CBAV. PMID- 21980333 TI - Clinical and virological factors associated with viremia in pandemic influenza A/H1N1/2009 virus infection. AB - BACKGROUND: Positive detection of viral RNA in blood and other non-respiratory specimens occurs in severe human influenza A/H5N1 viral infection but is not known to occur commonly in seasonal human influenza infection. Recently, viral RNA was detected in the blood of patients suffering from severe pandemic influenza A/H1N1/2009 viral infection, although the significance of viremia had not been previously studied. Our study aims to explore the clinical and virological factors associated with pandemic influenza A/H1N1/2009 viremia and to determine its clinical significance. METHODOLOGY/PRINCIPAL FINDINGS: Clinical data of patients admitted to hospitals in Hong Kong between May 2009 and April 2010 and tested positive for pandemic influenza A/H1N1/2009 was collected. Viral RNA was detected by reverse-transcription polymerase chain reactions (RT-PCR) targeting the matrix (M) and HA genes of pandemic influenza A/H1N1/2009 virus from the following specimens: nasopharyngeal aspirate (NPA), endotracheal aspirate (ETA), blood, stool and rectal swab. Stool and/ or rectal swab was obtained only if the patient complained of any gastrointestinal symptoms. A total of 139 patients were included in the study, with viral RNA being detected in the blood of 14 patients by RT-PCR. The occurrence of viremia was strongly associated with a severe clinical presentation and a higher mortality rate, although the latter association was not statistically significant. D222G/N quasispecies were observed in 90% of the blood samples. CONCLUSION: Presence of pandemic influenza A/H1N1/2009 viremia is an indicator of disease severity and strongly associated with D222G/N mutation in the viral hemagglutinin protein. PMID- 21980334 TI - Fine-tuning and the stability of recurrent neural networks. AB - A central criticism of standard theoretical approaches to constructing stable, recurrent model networks is that the synaptic connection weights need to be finely-tuned. This criticism is severe because proposed rules for learning these weights have been shown to have various limitations to their biological plausibility. Hence it is unlikely that such rules are used to continuously fine tune the network in vivo. We describe a learning rule that is able to tune synaptic weights in a biologically plausible manner. We demonstrate and test this rule in the context of the oculomotor integrator, showing that only known neural signals are needed to tune the weights. We demonstrate that the rule appropriately accounts for a wide variety of experimental results, and is robust under several kinds of perturbation. Furthermore, we show that the rule is able to achieve stability as good as or better than that provided by the linearly optimal weights often used in recurrent models of the integrator. Finally, we discuss how this rule can be generalized to tune a wide variety of recurrent attractor networks, such as those found in head direction and path integration systems, suggesting that it may be used to tune a wide variety of stable neural systems. PMID- 21980335 TI - A quantitative theory of solid tumor growth, metabolic rate and vascularization. AB - The relationships between cellular, structural and dynamical properties of tumors have traditionally been studied separately. Here, we construct a quantitative, predictive theory of solid tumor growth, metabolic rate, vascularization and necrosis that integrates the relationships between these properties. To accomplish this, we develop a comprehensive theory that describes the interface and integration of the tumor vascular network and resource supply with the cardiovascular system of the host. Our theory enables a quantitative understanding of how cells, tissues, and vascular networks act together across multiple scales by building on recent theoretical advances in modeling both healthy vasculature and the detailed processes of angiogenesis and tumor growth. The theory explicitly relates tumor vascularization and growth to metabolic rate, and yields extensive predictions for tumor properties, including growth rates, metabolic rates, degree of necrosis, blood flow rates and vessel sizes. Besides these quantitative predictions, we explain how growth rates depend on capillary density and metabolic rate, and why similar tumors grow slower and occur less frequently in larger animals, shedding light on Peto's paradox. Various implications for potential therapeutic strategies and further research are discussed. PMID- 21980336 TI - Isolation of a human anti-HIV gp41 membrane proximal region neutralizing antibody by antigen-specific single B cell sorting. AB - Broadly neutralizing antibodies are not commonly produced in HIV-1 infected individuals nor by experimental HIV-1 vaccines. When these antibodies do occur, it is important to be able to isolate and characterize them to provide clues for vaccine design. CAP206 is a South African subtype C HIV-1-infected individual previously shown to have broadly neutralizing plasma antibodies targeting the envelope gp41 distal membrane proximal external region (MPER). We have now used a fluoresceinated peptide tetramer antigen with specific cell sorting to isolate a human neutralizing monoclonal antibody (mAb) against the HIV-1 envelope gp41 MPER. The isolated recombinant mAb, CAP206-CH12, utilized a portion of the distal MPER (HXB2 amino acid residues, 673-680) and neutralized a subset of HIV-1 pseudoviruses sensitive to CAP206 plasma antibodies. Interestingly, this mAb was polyreactive and used the same germ-line variable heavy (V(H)1-69) and variable kappa light chain (V(K)3-20) gene families as the prototype broadly neutralizing anti-MPER mAb, 4E10 (residues 672-680). These data indicate that there are multiple immunogenic targets in the C-terminus of the MPER of HIV-1 gp41 envelope and suggests that gp41 neutralizing epitopes may interact with a restricted set of naive B cells during HIV-1 infection. PMID- 21980337 TI - Sphingomyelin synthases regulate protein trafficking and secretion. AB - Sphingomyelin synthases (SMS1 and 2) represent a class of enzymes that transfer a phosphocholine moiety from phosphatidylcholine onto ceramide thus producing sphingomyelin and diacylglycerol (DAG). SMS1 localizes at the Golgi while SMS2 localizes both at the Golgi and the plasma membrane. Previous studies from our laboratory showed that modulation of SMS1 and, to a lesser extent, of SMS2 affected the formation of DAG at the Golgi apparatus. As a consequence, down regulation of SMS1 and SMS2 reduced the localization of the DAG-binding protein, protein kinase D (PKD), to the Golgi. Since PKD recruitment to the Golgi has been implicated in cellular secretion through the trans golgi network (TGN), the effect of down-regulation of SMSs on TGN-to-plasma membrane trafficking was studied. Down regulation of either SMS1 or SMS2 significantly retarded trafficking of the reporter protein vesicular stomatitis virus G protein tagged with GFP (VSVG-GFP) from the TGN to the cell surface. Inhibition of SMSs also induced tubular protrusions from the trans Golgi network reminiscent of inhibited TGN membrane fission. Since a recent study demonstrated the requirement of PKD activity for insulin secretion in beta cells, we tested the function of SMS in this model. Inhibition of SMS significantly reduced insulin secretion in rat INS 1 cells. Taken together these results provide the first direct evidence that both enzymes (SMS1 and 2) are capable of regulating TGN-mediated protein trafficking and secretion, functions that are compatible with PKD being a down-stream target for SMSs in the Golgi. PMID- 21980338 TI - A place to hide in the home-cage decreases yolk androgen levels and offspring emotional reactivity in Japanese quail. AB - An animal's emotional responses are the result of its cognitive appraisal of a situation. This appraisal is notably influenced by the possibility of an individual to exert control over an aversive event. Although the fact that environment controllability decreases emotional responses in animals is well established, far less is known about its potential trans-generational effects. As the levels of avian yolk hormones can vary according to the mother's environment, we hypothesized that housing environment of mothers would modulate the quality of her eggs and in turn her offspring's behaviour. Two groups of female Japanese quail were constituted: a group that had access to a place to hide in their home cage (Hd, n = 20) and a group that had nowhere to hide (NoHd, n = 20) when stressed. Both groups were submitted to daily human disturbances for a twenty-day period. Hd females produced eggs with both less testosterone and androstenedione than did NoHd females. The emotional and social reactivity of Hd females' offspring were lower and their growth was slower than those of NoHd females' offspring. Our results show that a minor difference in housing environment had substantial effects on eggs and offspring. The presence of a shelter probably helped quail to cope with daily human disturbances, producing less reactive offspring. This transgenerational effect caused by an opportunity to hide could lead to applications in care of laboratory animals, conservation biology and animal welfare. PMID- 21980340 TI - A global clustering algorithm to identify long intergenic non-coding RNA--with applications in mouse macrophages. AB - Identification of diffuse signals from the chromatin immunoprecipitation and high throughput massively parallel sequencing (ChIP-Seq) technology poses significant computational challenges, and there are few methods currently available. We present a novel global clustering approach to enrich diffuse CHIP-Seq signals of RNA polymerase II and histone 3 lysine 4 trimethylation (H3K4Me3) and apply it to identify putative long intergenic non-coding RNAs (lincRNAs) in macrophage cells. Our global clustering method compares favorably to the local clustering method SICER that was also designed to identify diffuse CHIP-Seq signals. The validity of the algorithm is confirmed at several levels. First, 8 out of a total of 11 selected putative lincRNA regions in primary macrophages respond to lipopolysaccharides (LPS) treatment as predicted by our computational method. Second, the genes nearest to lincRNAs are enriched with biological functions related to metabolic processes under resting conditions but with developmental and immune-related functions under LPS treatment. Third, the putative lincRNAs have conserved promoters, modestly conserved exons, and expected secondary structures by prediction. Last, they are enriched with motifs of transcription factors such as PU.1 and AP.1, previously shown to be important lineage determining factors in macrophages, and 83% of them overlap with distal enhancers markers. In summary, GCLS based on RNA polymerase II and H3K4Me3 CHIP-Seq method can effectively detect putative lincRNAs that exhibit expected characteristics, as exemplified by macrophages in the study. PMID- 21980339 TI - Invasion and persistence of infectious agents in fragmented host populations. AB - One of the important questions in understanding infectious diseases and their prevention and control is how infectious agents can invade and become endemic in a host population. A ubiquitous feature of natural populations is that they are spatially fragmented, resulting in relatively homogeneous local populations inhabiting patches connected by the migration of hosts. Such fragmented population structures are studied extensively with metapopulation models. Being able to define and calculate an indicator for the success of invasion and persistence of an infectious agent is essential for obtaining general qualitative insights into infection dynamics, for the comparison of prevention and control scenarios, and for quantitative insights into specific systems. For homogeneous populations, the basic reproduction ratio R(0) plays this role. For metapopulations, defining such an 'invasion indicator' is not straightforward. Some indicators have been defined for specific situations, e.g., the household reproduction number R*. However, these existing indicators often fail to account for host demography and especially host migration. Here we show how to calculate a more broadly applicable indicator R(m) for the invasion and persistence of infectious agents in a host metapopulation of equally connected patches, for a wide range of possible epidemiological models. A strong feature of our method is that it explicitly accounts for host demography and host migration. Using a simple compartmental system as an example, we illustrate how R(m) can be calculated and expressed in terms of the key determinants of epidemiological dynamics. PMID- 21980342 TI - Structural perturbations to population skeletons: transient dynamics, coexistence of attractors and the rarity of chaos. AB - BACKGROUND: Simple models of insect populations with non-overlapping generations have been instrumental in understanding the mechanisms behind population cycles, including wild (chaotic) fluctuations. The presence of deterministic chaos in natural populations, however, has never been unequivocally accepted. Recently, it has been proposed that the application of chaos control theory can be useful in unravelling the complexity observed in real population data. This approach is based on structural perturbations to simple population models (population skeletons). The mechanism behind such perturbations to control chaotic dynamics thus far is model dependent and constant (in size and direction) through time. In addition, the outcome of such structurally perturbed models is [almost] always equilibrium type, which fails to commensurate with the patterns observed in population data. METHODOLOGY/PRINCIPAL FINDINGS: We present a proportional feedback mechanism that is independent of model formulation and capable of perturbing population skeletons in an evolutionary way, as opposed to requiring constant feedbacks. We observe the same repertoire of patterns, from equilibrium states to non-chaotic aperiodic oscillations to chaotic behaviour, across different population models, in agreement with observations in real population data. Model outputs also indicate the existence of multiple attractors in some parameter regimes and this coexistence is found to depend on initial population densities or the duration of transient dynamics. Our results suggest that such a feedback mechanism may enable a better understanding of the regulatory processes in natural populations. PMID- 21980341 TI - Photoreceptor cell death, proliferation and formation of hybrid rod/S-cone photoreceptors in the degenerating STK38L mutant retina. AB - A homozygous mutation in STK38L in dogs impairs the late phase of photoreceptor development, and is followed by photoreceptor cell death (TUNEL) and proliferation (PCNA, PHH3) events that occur independently in different cells between 7-14 weeks of age. During this period, the outer nuclear layer (ONL) cell number is unchanged. The dividing cells are of photoreceptor origin, have rod opsin labeling, and do not label with markers specific for macrophages/microglia (CD18) or Muller cells (glutamine synthetase, PAX6). Nestin labeling is absent from the ONL although it labels the peripheral retina and ciliary marginal zone equally in normals and mutants. Cell proliferation is associated with increased cyclin A1 and LATS1 mRNA expression, but CRX protein expression is unchanged. Coincident with photoreceptor proliferation is a change in the photoreceptor population. Prior to cell death the photoreceptor mosaic is composed of L/M- and S-cones, and rods. After proliferation, both cone types remain, but the majority of rods are now hybrid photoreceptors that express rod opsin and, to a lesser extent, cone S-opsin, and lack NR2E3 expression. The hybrid photoreceptors renew their outer segments diffusely, a characteristic of cones. The results indicate the capacity for terminally differentiated, albeit mutant, photoreceptors to divide with mutations in this novel retinal degeneration gene. PMID- 21980343 TI - Detectability counts when assessing populations for biodiversity targets. AB - Efficient, practical and accurate estimates of population parameters are a necessary basis for effective conservation action to meet biodiversity targets. The brown hare is representative of many European farmland species: historically widespread and abundant but having undergone rapid declines as a result of agricultural intensification. As a priority species in the UK Biodiversity Action Plan, it has national targets for population increase that are part of wider national environmental indicators. Previous research has indicated that brown hare declines have been greatest in pastural landscapes and that gains might be made by focussing conservation effort there. We therefore used hares in pastural landscapes to examine how basic changes in survey methodology can affect the precision of population density estimates and related these to national targets for biodiversity conservation in the UK. Line transects for hares carried out at night resulted in higher numbers of detections, had better-fitting detection functions and provided more robust density estimates with lower effort than those during the day, due primarily to the increased probability of detection of hares at night and the nature of hare responses to the observer. Hare spring densities varied widely within a single region, with a pooled mean of 20.6 hares km(-2), significantly higher than the reported national average of hares in pastures of 3.3 hares km(-2). The high number of encounters allowed us to resolve hare densities at site, season and year scales. We demonstrate how survey conduct can impact on data quantity and quality with implications for setting and monitoring biodiversity targets. Our case study of the brown hare provides evidence that for wildlife species with low detectability, large scale volunteer-based monitoring programmes, either species specific or generalist, might be more successfully and efficiently carried out by a small number of trained personnel able to employ methods that maximise detectability. PMID- 21980344 TI - Robustness analysis and behavior discrimination in enzymatic reaction networks. AB - Characterizing the behavior and robustness of enzymatic networks with numerous variables and unknown parameter values is a major challenge in biology, especially when some enzymes have counter-intuitive properties or switch-like behavior between activation and inhibition. In this paper, we propose new methodological and tool-supported contributions, based on the intuitive formalism of temporal logic, to express in a rigorous manner arbitrarily complex dynamical properties. Our multi-step analysis allows efficient sampling of the parameter space in order to define feasible regions in which the model exhibits imposed or experimentally observed behaviors. In a first step, an algorithmic methodology involving sensitivity analysis is conducted to determine bifurcation thresholds for a limited number of model parameters or initial conditions. In a second step, this boundary detection is supplemented by a global robustness analysis, based on quasi-Monte Carlo approach that takes into account all model parameters. We apply this method to a well-documented enzymatic reaction network describing collagen proteolysis by matrix metalloproteinase MMP2 and membrane type 1 metalloproteinase (MT1-MMP) in the presence of tissue inhibitor of metalloproteinase TIMP2. For this model, our method provides an extended analysis and quantification of network robustness toward paradoxical TIMP2 switching activity between activation or inhibition of MMP2 production. Further implication of our approach is illustrated by demonstrating and analyzing the possible existence of oscillatory behaviors when considering an extended open configuration of the enzymatic network. Notably, we construct bifurcation diagrams that specify key parameters values controlling the co-existence of stable steady and non-steady oscillatory proteolytic dynamics. PMID- 21980345 TI - Targeting KSHV/HHV-8 latency with COX-2 selective inhibitor nimesulide: a potential chemotherapeutic modality for primary effusion lymphoma. AB - The significance of inflammation in KSHV biology and tumorigenesis prompted us to examine the role of COX-2 in primary effusion lymphoma (PEL), an aggressive AIDS linked KSHV-associated non-Hodgkin's lymphoma (NHL) using nimesulide, a well known COX-2 specific NSAID. We demonstrate that (1) nimesulide is efficacious in inducing proliferation arrest in PEL (KSHV+/EBV-; BCBL-1 and BC-3, KSHV+/EBV+; JSC-1), EBV-infected (KSHV-/EBV+; Raji) and non-infected (KSHV-/EBV-; Akata, Loukes, Ramos, BJAB) high malignancy human Burkitt's lymphoma (BL) as well as KSHV-/EBV+ lymphoblastoid (LCL) cell lines; (2) nimesulide is selectively toxic to KSHV infected endothelial cells (TIVE-LTC) compared to TIVE and primary endothelial cells (HMVEC-d); (3) nimesulide reduced KSHV latent gene expression, disrupted p53-LANA-1 protein complexes, and activated the p53/p21 tumor suppressor pathway; (4) COX-2 inhibition down-regulated cell survival kinases (p Akt and p-GSK-3beta), an angiogenic factor (VEGF-C), PEL defining genes (syndecan 1, aquaporin-3, and vitamin-D3 receptor) and cell cycle proteins such as cyclins E/A and cdc25C; (5) nimesulide induced sustained cell death and G1 arrest in BCBL 1 cells; (6) nimesulide substantially reduced the colony forming capacity of BCBL 1 cells. Overall, our studies provide a comprehensive molecular framework linking COX-2 with PEL pathogenesis and identify the chemotherapeutic potential of nimesulide in treating PEL. PMID- 21980346 TI - CdSe quantum dot (QD)-induced morphological and functional impairments to liver in mice. AB - Quantum dots (QDs), as unique nanoparticle probes, have been used in in vivo fluorescence imaging such as cancers. Due to the novel characteristics in fluorescence, QDs represent a family of promising substances to be used in experimental and clinical imaging. Thus far, the toxicity and harmful health effects from exposure (including environmental exposure) to QDs are not recognized, but are largely concerned by the public. To assess the biological effects of QDs, we established a mouse model of acute and chronic exposure to QDs. Results from the present study suggested that QD particles could readily spread into various organs, and liver was the major organ for QD accumulation in mice from both the acute and chronic exposure. QDs caused significant impairments to livers from mice with both acute and chronic QD exposure as reflected by morphological alternation to the hepatic lobules and increased oxidative stress. Moreover, QDs remarkably induced the production of intracellular reactive oxygen species (ROS) along with cytotoxicity, as characterized by a significant increase of the malondialdehyde (MDA) level within hepatocytes. However, the increase of the MDA level in response to QD treatment could be partially blunted by the pre treatment of cells with beta-mercaptoethanol (beta-ME). These data suggested ROS played a crucial role in causing oxidative stress-associated cellular damage from QD exposure; nevertheless other unidentified mediators might also be involved in QD-mediated cellular impairments. Importantly, we demonstrated that the hepatoxicity caused by QDs in vivo and in vitro was much greater than that induced by cadmium ions at a similar or even a higher dose. Taken together, the mechanism underlying QD-mediated biological influences might derive from the toxicity of QD particles themselves, and from free cadmium ions liberated from QDs as well. PMID- 21980347 TI - Lymnaea schirazensis, an overlooked snail distorting fascioliasis data: genotype, phenotype, ecology, worldwide spread, susceptibility, applicability. AB - BACKGROUND: Lymnaeid snails transmit medical and veterinary important trematodiases, mainly fascioliasis. Vector specificity of fasciolid parasites defines disease distribution and characteristics. Different lymnaeid species appear linked to different transmission and epidemiological patterns. Pronounced susceptibility differences to absolute resistance have been described among lymnaeid populations. When assessing disease characteristics in different endemic areas, unexpected results were obtained in studies on lymnaeid susceptibility to Fasciola. We undertook studies to understand this disease transmission heterogeneity. METHODOLOGY/PRINCIPAL FINDINGS: A ten-year study in Iran, Egypt, Spain, the Dominican Republic, Mexico, Venezuela, Ecuador and Peru, demonstrated that such heterogeneity is not due to susceptibility differences, but to a hitherto overlooked cryptic species, Lymnaea schirazensis, confused with the main vector Galba truncatula and/or other Galba/Fossaria vectors. Nuclear rDNA and mtDNA sequences and phylogenetic reconstruction highlighted an old evolutionary divergence from other Galba/Fossaria species, and a low intraspecific variability suggesting a recent spread from one geographical source. Morphometry, anatomy and egg cluster analyses allowed for phenotypic differentiation. Selfing, egg laying, and habitat characteristics indicated a migration capacity by passive transport. Studies showed that it is not a vector species (n = 8572 field collected, 20 populations): snail finding and penetration by F. hepatica miracidium occur but never lead to cercarial production (n = 338 experimentally infected). CONCLUSIONS/SIGNIFICANCE: This species has been distorting fasciolid specificity/susceptibility and fascioliasis geographical distribution data. Hence, a large body of literature on G. truncatula should be revised. Its existence has henceforth to be considered in research. Genetic data on livestock, archeology and history along the 10,000-year post-domestication period explain its wide spread from the Neolithic Fertile Crescent. It is an efficient biomarker for the follow-up of livestock movements, a crucial aspect in fascioliasis emergence. It offers an outstanding laboratory model for genetic studies on susceptibility/resistance in F. hepatica/lymnaeid interaction, a field of applied research with disease control perspectives. PMID- 21980348 TI - Genome-wide assessment for genetic variants associated with ventricular dysfunction after primary coronary artery bypass graft surgery. AB - BACKGROUND: Postoperative ventricular dysfunction (VnD) occurs in 9-20% of coronary artery bypass graft (CABG) surgical patients and is associated with increased postoperative morbidity and mortality. Understanding genetic causes of postoperative VnD should enhance patient risk stratification and improve treatment and prevention strategies. We aimed to determine if genetic variants associate with occurrence of in-hospital VnD after CABG surgery. METHODS: A genome-wide association study identified single nucleotide polymorphisms (SNPs) associated with postoperative VnD in male subjects of European ancestry undergoing isolated primary CABG surgery with cardiopulmonary bypass. VnD was defined as the need for >=2 inotropes or mechanical ventricular support after CABG surgery. Validated SNPs were assessed further in two replication CABG cohorts and meta-analysis was performed. RESULTS: Over 100 SNPs were associated with VnD (P<10(-4)), with one SNP (rs17691914) encoded at 3p22.3 reaching genome wide significance (P(additive model) = 2.14*10(-8)). Meta-analysis of validation and replication study data for 17 SNPs identified three SNPs associated with increased risk for developing postoperative VnD after adjusting for clinical risk factors. These SNPs are located at 3p22.3 (rs17691914, OR(additive model) = 2.01, P = 0.0002), 3p14.2 (rs17061085, OR(additive model) = 1.70, P = 0.0001) and 11q23.2 (rs12279572, OR(recessive model) = 2.19, P = 0.001). CONCLUSIONS: No SNPs were consistently associated with strong risk (OR(additive model)>2.1) of developing in-hospital VnD after CABG surgery. However, three genetic loci identified by meta-analysis were more modestly associated with development of postoperative VnD. Studies of larger cohorts to assess these loci as well as to define other genetic mechanisms and related biology that link genetic variants to postoperative ventricular dysfunction are warranted. PMID- 21980349 TI - Hemispheric asymmetries in speech perception: sense, nonsense and modulations. AB - BACKGROUND: The well-established left hemisphere specialisation for language processing has long been claimed to be based on a low-level auditory specialization for specific acoustic features in speech, particularly regarding 'rapid temporal processing'. METHODOLOGY: A novel analysis/synthesis technique was used to construct a variety of sounds based on simple sentences which could be manipulated in spectro-temporal complexity, and whether they were intelligible or not. All sounds consisted of two noise-excited spectral prominences (based on the lower two formants in the original speech) which could be static or varying in frequency and/or amplitude independently. Dynamically varying both acoustic features based on the same sentence led to intelligible speech but when either or both acoustic features were static, the stimuli were not intelligible. Using the frequency dynamics from one sentence with the amplitude dynamics of another led to unintelligible sounds of comparable spectro-temporal complexity to the intelligible ones. Positron emission tomography (PET) was used to compare which brain regions were active when participants listened to the different sounds. CONCLUSIONS: Neural activity to spectral and amplitude modulations sufficient to support speech intelligibility (without actually being intelligible) was seen bilaterally, with a right temporal lobe dominance. A left dominant response was seen only to intelligible sounds. It thus appears that the left hemisphere specialisation for speech is based on the linguistic properties of utterances, not on particular acoustic features. PMID- 21980350 TI - Identification and functional clustering of genes regulating muscle protein degradation from amongst the known C. elegans muscle mutants. AB - Loss of muscle mass via protein degradation is an important clinical problem but we know little of how muscle protein degradation is regulated genetically. To gain insight our labs developed C. elegans into a model for understanding the regulation of muscle protein degradation. Past studies uncovered novel functional roles for genes affecting muscle and/or involved in signalling in other cells or tissues. Here we examine most of the genes previously identified as the sites of mutations affecting muscle for novel roles in regulating degradation. We evaluate genomic (RNAi knockdown) approaches and combine them with our established genetic (mutant) and pharmacologic (drugs) approaches to examine these 159 genes. We find that RNAi usually recapitulates both organismal and sub-cellular mutant phenotypes but RNAi, unlike mutants, can frequently be used acutely to study gene function solely in differentiated muscle. In the majority of cases where RNAi does not produce organismal level phenotypes, sub-cellular defects can be detected; disrupted proteostasis is most commonly observed. We identify 48 genes in which mutation or RNAi knockdown causes excessive protein degradation; myofibrillar and/or mitochondrial morphologies are also disrupted in 19 of these 48 cases. These 48 genes appear to act via at least three sub-networks to control bulk degradation of protein in muscle cytosol. Attachment to the extracellular matrix regulates degradation via unidentified proteases and affects myofibrillar and mitochondrial morphology. Growth factor imbalance and calcium overload promote lysosome based degradation whereas calcium deficit promotes proteasome based degradation, in both cases myofibrillar and mitochondrial morphologies are largely unaffected. Our results provide a framework for effectively using RNAi to identify and functionally cluster novel regulators of degradation. This clustering allows prioritization of candidate genes/pathways for future mechanistic studies. PMID- 21980351 TI - Microsatellite support for active inbreeding in a cichlid fish. AB - In wild animal populations, the degree of inbreeding differs between species and within species between populations. Because mating with kin often results in inbreeding depression, observed inbreeding is usually regarded to be caused by limited outbreeding opportunities due to demographic factors like small population size or population substructuring. However, theory predicts inclusive benefits from mating with kin, and thus part of the observed variation in inbreeding might be due to active inbreeding preferences. Although some recent studies indeed report kin mating preferences, the evidence is still highly ambiguous. Here, we investigate inbreeding in a natural population of the West African cichlid fish Pelvicachromis taeniatus which showed clear kin mating preferences in standardized laboratory experiments but no inbreeding depression. The presented microsatellite analysis reveals that the natural population has, in comparison to two reference populations, a reduced allelic diversity (A = 3) resulting in a low heterozygosity (H(o) = 0.167) pointing to a highly inbred population. Furthermore, we found a significant heterozygote deficit not only at population (F(is) = 0.116) but also at subpopulation level (F(is) = 0.081) suggesting that inbreeding is not only a by-product of population substructuring but possibly a consequence of behavioral kin preferences. PMID- 21980352 TI - A differential network approach to exploring differences between biological states: an application to prediabetes. AB - BACKGROUND: Variations in the pattern of molecular associations are observed during disease development. The comprehensive analysis of molecular association patterns and their changes in relation to different physiological conditions can yield insight into the biological basis of disease-specific phenotype variation. METHODOLOGY: Here, we introduce a formal statistical method for the differential analysis of molecular associations via network representation. We illustrate our approach with extensive data on lipoprotein subclasses measured by NMR spectroscopy in 4,406 individuals with normal fasting glucose, and 531 subjects with impaired fasting glucose (prediabetes). We estimate the pair-wise association between measures using shrinkage estimates of partial correlations and build the differential network based on this measure of association. We explore the topological properties of the inferred network to gain insight into important metabolic differences between individuals with normal fasting glucose and prediabetes. CONCLUSIONS/SIGNIFICANCE: Differential networks provide new insights characterizing differences in biological states. Based on conventional statistical methods, few differences in concentration levels of lipoprotein subclasses were found between individuals with normal fasting glucose and individuals with prediabetes. By performing the differential analysis of networks, several characteristic changes in lipoprotein metabolism known to be related to diabetic dyslipidemias were identified. The results demonstrate the applicability of the new approach to identify key molecular changes inaccessible to standard approaches. PMID- 21980354 TI - Correlation of LNCR rasiRNAs expression with heterochromatin formation during development of the holocentric insect Spodoptera frugiperda. AB - Repeat-associated small interfering RNAs (rasiRNAs) are derived from various genomic repetitive elements and ensure genomic stability by silencing endogenous transposable elements. Here we describe a novel subset of 46 rasiRNAs named LNCR rasiRNAs due to their homology with one long non-coding RNA (LNCR) of Spodoptera frugiperda. LNCR operates as the intermediate of an unclassified transposable element (TE-LNCR). TE-LNCR is a very invasive transposable element, present in high copy numbers in the S. frugiperda genome. LNCR rasiRNAs are single-stranded RNAs without a prominent nucleotide motif, which are organized in two distinct, strand-specific clusters. The expression of LNCR and LNCR rasiRNAs is developmentally regulated. Formation of heterochromatin in the genomic region where three copies of the TE-LNCR are embedded was followed by chromatin immunoprecipitation (ChIP) and we observed this chromatin undergo dynamic changes during development. In summary, increased LNCR expression in certain developmental stages is followed by the appearance of a variety of LNCR rasiRNAs which appears to correlate with subsequent accumulation of a heterochromatic histone mark and silencing of the genomic region with TE-LNCR. These results support the notion that a repeat-associated small interfering RNA pathway is linked to heterochromatin formation and/or maintenance during development to establish repression of the TE-LNCR transposable element. This study provides insights into the rasiRNA silencing pathway and its role in the formation of fluctuating heterochromatin during the development of one holocentric organism. PMID- 21980353 TI - pubmed2ensembl: a resource for mining the biological literature on genes. AB - BACKGROUND: The last two decades have witnessed a dramatic acceleration in the production of genomic sequence information and publication of biomedical articles. Despite the fact that genome sequence data and publications are two of the most heavily relied-upon sources of information for many biologists, very little effort has been made to systematically integrate data from genomic sequences directly with the biological literature. For a limited number of model organisms dedicated teams manually curate publications about genes; however for species with no such dedicated staff many thousands of articles are never mapped to genes or genomic regions. METHODOLOGY/PRINCIPAL FINDINGS: To overcome the lack of integration between genomic data and biological literature, we have developed pubmed2ensembl (http://www.pubmed2ensembl.org), an extension to the BioMart system that links over 2,000,000 articles in PubMed to nearly 150,000 genes in Ensembl from 50 species. We use several sources of curated (e.g., Entrez Gene) and automatically generated (e.g., gene names extracted through text-mining on MEDLINE records) sources of gene-publication links, allowing users to filter and combine different data sources to suit their individual needs for information extraction and biological discovery. In addition to extending the Ensembl BioMart database to include published information on genes, we also implemented a scripting language for automated BioMart construction and a novel BioMart interface that allows text-based queries to be performed against PubMed and PubMed Central documents in conjunction with constraints on genomic features. Finally, we illustrate the potential of pubmed2ensembl through typical use cases that involve integrated queries across the biomedical literature and genomic data. CONCLUSION/SIGNIFICANCE: By allowing biologists to find the relevant literature on specific genomic regions or sets of functionally related genes more easily, pubmed2ensembl offers a much-needed genome informatics inspired solution to accessing the ever-increasing biomedical literature. PMID- 21980355 TI - When connectedness increases hemispatial neglect. AB - Patients with left neglect were tested with "chimeric" figures composed of the right and left halves of two different objects. The connectivity relation was modulated between the two half figures. For some displays, the two chimeric halves were separated by a small gap, while in others, the separate halves were connected by a line segment. In line with previous reports, performance on reporting the left half improved when the chimera were separated; but when a line connected the two separated halves the advantage was lost. If the connecting line was broken, the performance was again enhanced. The results suggest an important role for connectedness in the representation of perceptual objects and in the distribution of attention in neglect. PMID- 21980356 TI - Reliable detection of paternal SNPs within deletion breakpoints for non-invasive prenatal exclusion of homozygous alpha-thalassemia in maternal plasma. AB - Reliable detection of large deletions from cell-free fetal DNA (cffDNA) in maternal plasma is challenging, especially when both parents have the same deletion owing to a lack of specific markers for fetal genotyping. In order to evaluate the efficacy of a non-invasive prenatal diagnosis (NIPD) test to exclude alpha-thalassemia major that uses SNPs linked to the normal paternal alpha-globin allele, we established a novel protocol to reliably detect paternal SNPs within the (--(SEA)) breakpoints and performed evaluation of the diagnostic potential of the protocol in a total of 67 pregnancies, in whom plasma samples were collected prior to invasive obstetrics procedures in southern China. A group of nine SNPs identified within the deletion breakpoints were scanned to select the informative SNPs in each of the 67 couples DNA by multiplex PCR based mini-sequencing technique. The paternally inherited SNP allele from cffDNA was detected by allele specific real-time PCR. A protocol for reliable detection of paternal SNPs within the (--(SEA)) breakpoints was established and evaluation of the diagnostic potential of the protocol was performed in a total of 67 pregnancies. In 97% of the couples one or more different SNPs within the deletion breakpoint occurred between paternal and maternal alleles. Homozygosity for the (--(SEA)) deletion was accurately excluded in 33 out of 67 (49.3%, 95% CI, 25.4-78.6%) pregnancies through the implementation of the protocol. Protocol was completely concordant with the traditional reference methods, except for two cases that exhibited uncertain results due to sample hemolysis. This method could be used as a routine NIPD test to exclude gross fetal deletions in alpha-thalassemia major, and could further be employed to test for other diseases due to gene deletion. PMID- 21980357 TI - Fibronectin matrix assembly suppresses dispersal of glioblastoma cells. AB - Glioblastoma (GBM), the most aggressive and most common form of primary brain tumor, has a median survival of 12-15 months. Surgical excision, radiation and chemotherapy are rarely curative since tumor cells broadly disperse within the brain. Preventing dispersal could be of therapeutic benefit. Previous studies have reported that increased cell-cell cohesion can markedly reduce invasion by discouraging cell detachment from the tumor mass. We have previously reported that alpha5beta1 integrin-fibronectin interaction is a powerful mediator of indirect cell-cell cohesion and that the process of fibronectin matrix assembly (FNMA) is crucial to establishing strong bonds between cells in 3D tumor-like spheroids. Here, we explore a potential role for FNMA in preventing dispersal of GBM cells from a tumor-like mass. Using a series of GBM-derived cell lines we developed an in vitro assay to measure the dispersal velocity of aggregates on a solid substrate. Despite their similar pathologic grade, aggregates from these lines spread at markedly different rates. Spreading velocity is inversely proportional to capacity for FNMA and restoring FNMA in GBM cells markedly reduces spreading velocity by keeping cells more connected. Blocking FNMA using the 70 KDa fibronectin fragment in FNMA-restored cells rescues spreading velocity, establishing a functional role for FNMA in mediating dispersal. Collectively, the data support a functional causation between restoration of FNMA and decreased dispersal velocity. This is a first demonstration that FNMA can play a suppressive role in GBM dispersal. PMID- 21980358 TI - Loss of p53 Ser18 and Atm results in embryonic lethality without cooperation in tumorigenesis. AB - Phosphorylation at murine Serine 18 (human Serine 15) is a critical regulatory process for the tumor suppressor function of p53. p53Ser18 residue is a substrate for ataxia-telangiectasia mutated (ATM) and ATM-related (ATR) protein kinases. Studies of mice with a germ-line mutation that replaces Ser18 with Ala (p53(S18A) mice) have demonstrated that loss of phosphorylation of p53Ser18 leads to the development of tumors, including lymphomas, fibrosarcomas, leukemia and leiomyosarcomas. The predominant lymphoma is B-cell lymphoma, which is in contrast to the lymphomas observed in Atm(-/-) animals. This observation and the fact that multiple kinases phosphorylate p53Ser18 suggest Atm-independent tumor suppressive functions of p53Ser18. Therefore, in order to examine p53Ser18 function in relationship to ATM, we analyzed the lifespan and tumorigenesis of mice with combined mutations in p53Ser18 and Atm. Surprisingly, we observed no cooperation in survival and tumorigenesis in compound p53(S18A) and Atm(-/-) animals. However, we observed embryonic lethality in the compound mutant animals. In addition, the homozygous p53Ser18 mutant allele impacted the weight of Atm(-/ ) animals. These studies examine the genetic interaction of p53Ser18 and Atm in vivo. Furthermore, these studies demonstrate a role of p53Ser18 in regulating embryonic survival and motor coordination. PMID- 21980359 TI - Transcranial magnetic stimulation intensities in cognitive paradigms. AB - BACKGROUND: Transcranial magnetic stimulation (TMS) has become an important experimental tool for exploring the brain's functional anatomy. As TMS interferes with neural activity, the hypothetical function of the stimulated area can thus be tested. One unresolved methodological issue in TMS experiments is the question of how to adequately calibrate stimulation intensities. The motor threshold (MT) is often taken as a reference for individually adapted stimulation intensities in TMS experiments, even if they do not involve the motor system. The aim of the present study was to evaluate whether it is reasonable to adjust stimulation intensities in each subject to the individual MT if prefrontal regions are stimulated prior to the performance of a cognitive paradigm. METHODS AND FINDINGS: Repetitive TMS (rTMS) was applied prior to a working memory task, either at the 'fixed' intensity of 40% maximum stimulator output (MSO), or individually adapted at 90% of the subject's MT. Stimulation was applied to a target region in the left posterior middle frontal gyrus (pMFG), as indicated by a functional magnetic resonance imaging (fMRI) localizer acquired beforehand, or to a control site (vertex). Results show that MT predicted the effect size after stimulating subjects with the fixed intensity (i.e., subjects with a low MT showed a greater behavioral effect). Nevertheless, the individual adaptation of intensities did not lead to stable effects. CONCLUSION: Therefore, we suggest assessing MT and account for it as a measure for general cortical TMS susceptibility, even if TMS is applied outside the motor domain. PMID- 21980360 TI - Bone related health status in adolescent cyclists. AB - PURPOSE: To describe bone status and analyse bone mass in adolescent cyclists. METHODS: Male road cyclists (n = 22) who had been training for a minimum of 2 years and a maximum of 7 years with a volume of 10 h/w, were compared to age matched controls (n = 22) involved in recreational sports activities. Subjects were divided in 2 groups based on age: adolescents under 17 yrs (cyclists, n = 11; controls, n = 13) and over 17 yrs (cyclists, n = 11; controls, n = 9). Peak oxygen uptake (VO(2)max) was measured on a cycloergometer. Whole body, lumbar spine, and hip bone mineral content (BMC), density (BMD) and bone area were assessed using dual x-ray absorptiometry (DXA). Volumetric BMD (vBMD) and bone mineral apparent density (BMAD) were also estimated. RESULTS: The BMC of cyclists was lower for the whole body, pelvis, femoral neck and legs; BMD for the pelvis, hip, legs and whole body and legs bone area was lower but higher in the hip area (all, P<=0.05) after adjusting by lean mass and height. The BMC of young cyclists was 10% lower in the leg and 8% higher in the hip area than young controls (P<=0.05). The BMC of cyclists over 17 yrs was 26.5%, 15.8% and 14.4% lower BMC at the pelvis, femoral neck and legs respectively while the BMD was 8.9% to 24.5% lower for the whole body, pelvis, total hip, trochanter, intertrochanter, femoral neck and legs and 17.1% lower the vBMD at the femoral neck (all P<=0.05). Grouped by age interaction was found in both pelvis and hip BMC and BMD and in femoral neck vBMD (all P<=0.05). CONCLUSION: Cycling performed throughout adolescence may negatively affect bone health, then compromising the acquisition of peak bone mass. PMID- 21980361 TI - Adenoviruses in lymphocytes of the human gastro-intestinal tract. AB - OBJECTIVE: Persistent adenoviral shedding in stools is known to occur past convalescence following acute adenoviral infections. We wished to establish the frequency with which adenoviruses may colonize the gut in normal human subjects. METHODS: The presence of adenoviral DNA in intestinal specimens obtained at surgery or autopsy was tested using a nested PCR method. The amplified adenoviral DNA sequences were compared to each other and to known adenoviral species. Lamina propria lymphocytes (LPLs) were isolated from the specimens and the adenoviral copy numbers in the CD4+ and CD8+ fractions were determined by quantitative PCR. Adenoviral gene expression was tested by amplification of adenoviral mRNA. RESULTS: Intestinal tissue from 21 of 58 donors and LPLs from 21 of 24 donors were positive for the presence of adenoviral DNA. The majority of the sequences could be assigned to adenoviral species E, although species B and C sequences were also common. Multiple sequences were often present in the same sample. Forty one non-identical sequences were identified from 39 different tissue donors. Quantitative PCR for adenoviral DNA in CD4+ and CD8+ fractions of LPLs showed adenoviral DNA to be present in both cell types and ranged from a few hundred to several million copies per million cells on average. Active adenoviral gene expression as evidenced by the presence of adenoviral messenger RNA in intestinal lymphocytes was demonstrated in 9 of the 11 donors tested. CONCLUSION: Adenoviral DNA is highly prevalent in lymphocytes from the gastro-intestinal tract indicating that adenoviruses may be part of the normal gut flora. PMID- 21980362 TI - Repeated exposure to methamphetamine, cocaine or morphine induces augmentation of dopamine release in rat mesocorticolimbic slice co-cultures. AB - Repeated intermittent exposure to psychostimulants and morphine leads to progressive augmentation of its locomotor activating effects in rodents. Accumulating evidence suggests the critical involvement of the mesocorticolimbic dopaminergic neurons, which project from the ventral tegmental area to the nucleus accumbens and the medial prefrontal cortex, in the behavioral sensitization. Here, we examined the acute and chronic effects of psychostimulants and morphine on dopamine release in a reconstructed mesocorticolimbic system comprised of a rat triple organotypic slice co-culture of the ventral tegmental area, nucleus accumbens and medial prefrontal cortex regions. Tyrosine hydroxylase-positive cell bodies were localized in the ventral tegmental area, and their neurites projected to the nucleus accumbens and medial prefrontal cortex regions. Acute treatment with methamphetamine (0.1-1000 uM), cocaine (0.1-300 uM) or morphine (0.1-100 uM) for 30 min increased extracellular dopamine levels in a concentration-dependent manner, while 3,4 methylenedioxyamphetamine (0.1-1000 uM) had little effect. Following repeated exposure to methamphetamine (10 uM) for 30 min every day for 6 days, the dopamine release gradually increased during the 30-min treatment. The augmentation of dopamine release was maintained even after the withdrawal of methamphetamine for 7 days. Similar augmentation was observed by repeated exposure to cocaine (1-300 uM) or morphine (10 and 100 uM). Furthermore, methamphetamine-induced augmentation of dopamine release was prevented by an NMDA receptor antagonist, MK 801 (10 uM), and was not observed in double slice co-cultures that excluded the medial prefrontal cortex slice. These results suggest that repeated psychostimulant- or morphine-induced augmentation of dopamine release, i.e. dopaminergic sensitization, was reproduced in a rat triple organotypic slice co cultures. In addition, the slice co-culture system revealed that the NMDA receptors and the medial prefrontal cortex play an essential role in the dopaminergic sensitization. This in vitro sensitization model provides a unique approach for studying mechanisms underlying behavioral sensitization to drugs of abuse. PMID- 21980363 TI - Quantitative analysis of the effect of cancer invasiveness and collagen concentration on 3D matrix remodeling. AB - Extracellular matrix (ECM) remodeling is a key component of cell migration and tumor metastasis, and has been associated with cancer progression. Despite the importance of matrix remodeling, systematic and quantitative studies on the process have largely been lacking. Furthermore, it remains unclear if the disrupted tensional homeostasis characteristic of malignancy is due to initially altered ECM and tissue properties, or to the alteration of the tissue by tumor cells. To explore these questions, we studied matrix remodeling by two different prostate cancer cell lines in a three-dimensional collagen system. Over one week, we monitored structural changes in gels of varying collagen content using confocal reflection microscopy and quantitative image analysis, tracking metrics of fibril fraction, pore size, and fiber length and diameter. Gels that were seeded with no cells (control), LNCaP cells, and DU-145 cells were quantitatively compared. Gels with higher collagen content initially had smaller pore sizes and higher fibril fractions, as expected. However, over time, LNCaP- and DU-145 populated matrices showed different structural properties compared both to each other and to the control gels, with LNCaP cells appearing to favor microenvironments with lower collagen fiber fractions and larger pores than DU 145 cells. We posit that the DU-145 cells' preference for denser matrices is due to their higher invasiveness and proteolytic capabilities. Inhibition of matrix proteases resulted in reduced fibril fractions for high concentration gels seeded with either cell type, supporting our hypothesis. Our novel quantitative results probe the dynamics of gel remodeling in three dimensions and suggest that prostate cancer cells remodel their ECM in a synergistic manner that is dependent on both initial matrix properties as well as their invasiveness. PMID- 21980364 TI - Multiple statistical analysis techniques corroborate intratumor heterogeneity in imaging mass spectrometry datasets of myxofibrosarcoma. AB - MALDI mass spectrometry can generate profiles that contain hundreds of biomolecular ions directly from tissue. Spatially-correlated analysis, MALDI imaging MS, can simultaneously reveal how each of these biomolecular ions varies in clinical tissue samples. The use of statistical data analysis tools to identify regions containing correlated mass spectrometry profiles is referred to as imaging MS-based molecular histology because of its ability to annotate tissues solely on the basis of the imaging MS data. Several reports have indicated that imaging MS-based molecular histology may be able to complement established histological and histochemical techniques by distinguishing between pathologies with overlapping/identical morphologies and revealing biomolecular intratumor heterogeneity. A data analysis pipeline that identifies regions of imaging MS datasets with correlated mass spectrometry profiles could lead to the development of novel methods for improved diagnosis (differentiating subgroups within distinct histological groups) and annotating the spatio-chemical makeup of tumors. Here it is demonstrated that highlighting the regions within imaging MS datasets whose mass spectrometry profiles were found to be correlated by five independent multivariate methods provides a consistently accurate summary of the spatio-chemical heterogeneity. The corroboration provided by using multiple multivariate methods, efficiently applied in an automated routine, provides assurance that the identified regions are indeed characterized by distinct mass spectrometry profiles, a crucial requirement for its development as a complementary histological tool. When simultaneously applied to imaging MS datasets from multiple patient samples of intermediate-grade myxofibrosarcoma, a heterogeneous soft tissue sarcoma, nodules with mass spectrometry profiles found to be distinct by five different multivariate methods were detected within morphologically identical regions of all patient tissue samples. To aid the further development of imaging MS based molecular histology as a complementary histological tool the Matlab code of the agreement analysis, instructions and a reduced dataset are included as supporting information. PMID- 21980365 TI - The haploinsufficient hematopoietic microenvironment is critical to the pathological fracture repair in murine models of neurofibromatosis type 1. AB - Germline mutations in the NF1 tumor suppressor gene cause neurofibromatosis type 1 (NF1), a complex genetic disorder with a high predisposition of numerous skeletal dysplasias including short stature, osteoporosis, kyphoscoliosis, and fracture non-union (pseudoarthrosis). We have developed murine models that phenocopy many of the skeletal dysplasias observed in NF1 patients, including reduced bone mass and fracture non-union. We also show that the development of these skeletal manifestations requires an Nf1 haploinsufficient background in addition to nullizygous loss of Nf1 in mesenchymal stem/progenitor cells (MSCs) and/or their progenies. This is replicated in two animal models of NF1, PeriCre(+);Nf1(flox/-) and Col2.3Cre(+);Nf1(flox/-) mice. Adoptive transfer experiments demonstrate a critical role of the Nf1+/- marrow microenvironment in the impaired fracture healing in both models and adoptive transfer of WT bone marrow cells improves fracture healing in these mice. To our knowledge, this is the first demonstration of a non-cell autonomous mechanism in non-malignant NF1 manifestations. Collectively, these data provide evidence of a combinatory effect between nullizygous loss of Nf1 in osteoblast progenitors and haploinsufficiency in hematopoietic cells in the development of non-malignant NF1 manifestations. PMID- 21980366 TI - Sleep-deprivation induces changes in GABA(B) and mGlu receptor expression and has consequences for synaptic long-term depression. AB - Long term depression (LTD) in the CA1 region of the hippocampus, induced with a 20-Hz, 30 s tetanus to Schaffer collaterals, is enhanced in sleep-deprived (SD) rats. In the present study, we investigated the role of metabotropic glutamate receptors (mGluRs), gamma-aminobutyric acid (GABA) B receptors (GABA(B)-Rs) and N methyl-D-aspartic acid receptors (NMDARs) in the LTD of the population excitatory postsynaptic potential (pEPSP). The requirement of Ca(2+) from L- and T-type voltage-gated calcium channels (VGCCs) and intracellular stores was also studied. Results indicate that mGluRs, a release of Ca(2+) from intracellular stores and GABA(B)-Rs are required for LTD. Interestingly, while mGlu1Rs seem to be involved in both short-term depression and LTD, mGlu5Rs appear to participate mostly in LTD. CGP 55845, a GABA(B)-R antagonist, partially suppressed LTD in normally sleeping (NS) rats, while completely blocking LTD in SD rats. Moreover, GS-39783, a positive allosteric modulator for GABA(B)-R, suppressed the pEPSP in SD, but not NS rats. Since both mGluRs and GABA(B)-Rs seem to be involved in the LTD, especially in SD rats, we examined if the receptor expression pattern and/or dimerization changed, using immunohistochemical, co-localization and co immunoprecipitation techniques. Sleep-deprivation induced an increase in the expression of GABA(B)-R1 and mGlu1alphaR in the CA1 region of the hippocampus. In addition, co-localization and heterodimerization between mGlu1alphaR/GABA(B)-R1 and mGlu1alphaR/GABA(B)-R2 is enhanced in SD rats. Taken together, our findings present a novel form of LTD sensitive to the activation of mGluRs and GABA(B)-Rs, and reveal, for the first time, that sleep-deprivation induces alterations in the expression and dimerization of these receptors. PMID- 21980367 TI - A new paleozoic Symmoriiformes (Chondrichthyes) from the late Carboniferous of Kansas (USA) and cladistic analysis of early chondrichthyans. AB - BACKGROUND: The relationships of cartilaginous fishes are discussed in the light of well preserved three-dimensional Paleozoic specimens. There is no consensus to date on the interrelationship of Paleozoic chondrichthyans, although three main phylogenetic hypotheses exist in the current literature: 1. the Paleozoic shark like chondrichthyans, such as the Symmoriiformes, are grouped along with the modern sharks (neoselachians) into a clade which is sister group of holocephalans; 2. the Symmoriiformes are related to holocephalans, whereas the other Paleozoic shark-like chondrichthyans are related to neoselachians; 3. many Paleozoic shark-like chondrichthyans, such as the Symmoriiformes, are stem chondrichthyans, whereas stem and crown holocephalans are sister group to the stem and crown neoselachians in a crown-chondrichthyan clade. This third hypothesis was proposed recently, based mainly on dental characters. METHODOLOGY/PRINCIPAL FINDINGS: On the basis of two well preserved chondrichthyan neurocrania from the Late Carboniferous of Kansas, USA, we describe here a new species of Symmoriiformes, Kawichthys moodiei gen. et sp. nov., which was investigated by means of computerized X-ray synchrotron microtomography. We present a new phylogenetic analysis based on neurocranial characters, which supports the third hypothesis and corroborates the hypothesis that crown-group chondrichthyans (Holocephali+Neoselachii) form a tightly-knit group within the chondrichthyan total group, by providing additional, non dental characters. CONCLUSIONS/SIGNIFICANCE: Our results highlight the importance of new well preserved Paleozoic fossils and new techniques of observation, and suggest that a new look at the synapomorphies of the crown-group chondrichthyans would be worthwhile in terms of understanding the adaptive significance of phylogenetically important characters. PMID- 21980368 TI - MicroRNAs associated with metastatic prostate cancer. AB - OBJECTIVE: Metastasis is the most common cause of death of prostate cancer patients. Identification of specific metastasis biomarkers and novel therapeutic targets is considered essential for improved prognosis and management of the disease. MicroRNAs (miRNAs) form a class of non-coding small RNA molecules considered to be key regulators of gene expression. Their dysregulation has been shown to play a role in cancer onset, progression and metastasis, and miRNAs represent a promising new class of cancer biomarkers. The objective of this study was to identify down- and up-regulated miRNAs in prostate cancer that could provide potential biomarkers and/or therapeutic targets for prostate cancer metastasis. METHODS: Next generation sequencing technology was applied to identify differentially expressed miRNAs in a transplantable metastatic versus a non-metastatic prostate cancer xenograft line, both derived from one patient's primary cancer. The xenografts were developed via subrenal capsule grafting of cancer tissue into NOD/SCID mice, a methodology that tends to preserve properties of the original cancers (e.g., tumor heterogeneity, genetic profiles). RESULTS: Differentially expressed known miRNAs, isomiRs and 36 novel miRNAs were identified. A number of these miRNAs (21/104) have previously been reported to show similar down- or up-regulation in prostate cancers relative to normal prostate tissue, and some of them (e.g., miR-16, miR-34a, miR-126*, miR-145, miR 205) have been linked to prostate cancer metastasis, supporting the validity of the analytical approach. CONCLUSIONS: The use of metastatic and non-metastatic prostate cancer subrenal capsule xenografts derived from one patient's cancer makes it likely that the differentially expressed miRNAs identified in this study include potential biomarkers and/or therapeutic targets for human prostate cancer metastasis. PMID- 21980369 TI - Universal stress proteins are important for oxidative and acid stress resistance and growth of Listeria monocytogenes EGD-e in vitro and in vivo. AB - BACKGROUND: Pathogenic bacteria maintain a multifaceted apparatus to resist damage caused by external stimuli. As part of this, the universal stress protein A (UspA) and its homologues, initially discovered in Escherichia coli K-12 were shown to possess an important role in stress resistance and growth in several bacterial species. METHODS AND FINDINGS: We conducted a study to assess the role of three homologous proteins containing the UspA domain in the facultative intracellular human pathogen Listeria monocytogenes under different stress conditions. The growth properties of three UspA deletion mutants (Deltalmo0515, Deltalmo1580 and Deltalmo2673) were examined either following challenge with a sublethal concentration of hydrogen peroxide or under acidic conditions. We also examined their ability for intracellular survival within murine macrophages. Virulence and growth of usp mutants were further characterized in invertebrate and vertebrate infection models. Tolerance to acidic stress was clearly reduced in Deltalmo1580 and Deltalmo0515, while oxidative stress dramatically diminished growth in all mutants. Survival within macrophages was significantly decreased in Deltalmo1580 and Deltalmo2673 as compared to the wild-type strain. Viability of infected Galleria mellonella larvae was markedly higher when injected with Deltalmo1580 or Deltalmo2673 as compared to wild-type strain inoculation, indicating impaired virulence of bacteria lacking these usp genes. Finally, we observed severely restricted growth of all chromosomal deletion mutants in mice livers and spleens as compared to the load of wild-type bacteria following infection. CONCLUSION: This work provides distinct evidence that universal stress proteins are strongly involved in listerial stress response and survival under both in vitro and in vivo growth conditions. PMID- 21980370 TI - Smart phone, smart science: how the use of smartphones can revolutionize research in cognitive science. AB - Investigating human cognitive faculties such as language, attention, and memory most often relies on testing small and homogeneous groups of volunteers coming to research facilities where they are asked to participate in behavioral experiments. We show that this limitation and sampling bias can be overcome by using smartphone technology to collect data in cognitive science experiments from thousands of subjects from all over the world. This mass coordinated use of smartphones creates a novel and powerful scientific "instrument" that yields the data necessary to test universal theories of cognition. This increase in power represents a potential revolution in cognitive science. PMID- 21980371 TI - Monilinia species causing brown rot of peach in China. AB - In this study, 145 peaches and nectarines displaying typical brown rot symptoms were collected from multiple provinces in China. A subsample of 26 single-spore isolates were characterized phylogenetically and morphologically to ascertain species. Phylogenetic analysis of internal transcribed spacer (ITS) regions 1 and 2, glyceraldehyde-3-phosphate dehydrogenase (G3PDH), beta-tubulin (TUB2) revealed the presence of three distinct Monilinia species. These species included Monilinia fructicola, Monilia mumecola, and a previously undescribed species designated Monilia yunnanensis sp. nov. While M. fructicola is a well-documented pathogen of Prunus persica in China, M. mumecola had primarily only been isolated from mume fruit in Japan. Koch's postulates for M. mumecola and M. yunnanensis were fulfilled confirming pathogenicity of the two species on peach. Phylogenetic analysis of ITS, G3PDH, and TUB2 sequences indicated that M. yunnanensis is most closely related to M. fructigena, a species widely prevalent in Europe. Interestingly, there were considerable differences in the exon/intron structure of the cytochrome b (Cyt b) gene between the two species. Morphological characteristics, including spore size, colony morphology, lesion growth rate, and sporulation, support the phylogenetic evidence suggesting the designation of M. yunnanensis as a new species. A new multiplex PCR method was developed to facilitate the detection of M. yunnanensis and differentiation of Monilinia spp. causing brown rot of peach in China. PMID- 21980372 TI - Intravascular food reward. AB - Consumption of calorie-containing sugars elicits appetitive behavioral responses and dopamine release in the ventral striatum, even in the absence of sweet-taste transduction machinery. However, it is unclear if such reward-related postingestive effects reflect preabsorptive or postabsorptive events. In support of the importance of postabsorptive glucose detection, we found that, in rat behavioral tests, high concentration glucose solutions administered in the jugular vein were sufficient to condition a side-bias. Additionally, a lower concentration glucose solution conditioned robust behavioral responses when administered in the hepatic-portal, but not the jugular vein. Furthermore, enteric administration of glucose at a concentration that is sufficient to elicit behavioral conditioning resulted in a glycemic profile similar to that observed after administration of the low concentration glucose solution in the hepatic portal, but not jugular vein. Finally using fast-scan cyclic voltammetry we found that, in accordance with behavioral findings, a low concentration glucose solution caused an increase in spontaneous dopamine release events in the nucleus accumbens shell when administered in the hepatic-portal, but not the jugular vein. These findings demonstrate that the postabsorptive effects of glucose are sufficient for the postingestive behavioral and dopaminergic reward-related responses that result from sugar consumption. Furthermore, glycemia levels in the hepatic-portal venous system contribute more significantly for this effect than systemic glycemia, arguing for the participation of an intra-abdominal visceral sensor for glucose. PMID- 21980373 TI - Efficacy of single-dose and triple-dose albendazole and mebendazole against soil transmitted helminths and Taenia spp.: a randomized controlled trial. AB - BACKGROUND: The control of soil-transmitted helminth (STH) infections currently relies on the large-scale administration of single-dose oral albendazole or mebendazole. However, these treatment regimens have limited efficacy against hookworm and Trichuris trichiura in terms of cure rates (CR), whereas fecal egg reduction rates (ERR) are generally high for all common STH species. We compared the efficacy of single-dose versus triple-dose treatment against hookworm and other STHs in a community-based randomized controlled trial in the People's Republic of China. METHODOLOGY/PRINCIPAL FINDINGS: The hookworm CR and fecal ERR were assessed in 314 individuals aged >=5 years who submitted two stool samples before and 3-4 weeks after administration of single-dose oral albendazole (400 mg) or mebendazole (500 mg) or triple-dose albendazole (3*400 mg over 3 consecutive days) or mebendazole (3*500 mg over 3 consecutive days). Efficacy against T. trichiura, Ascaris lumbricoides, and Taenia spp. was also assessed. ALBENDAZOLE CURED SIGNIFICANTLY MORE HOOKWORM INFECTIONS THAN MEBENDAZOLE IN BOTH TREATMENT REGIMENS (SINGLE DOSE: respective CRs 69% (95% confidence interval [CI]: 55-81%) and 29% (95% CI: 20-45%); triple dose: respective CRs 92% (95% CI: 81-98%) and 54% (95% CI: 46-71%)). ERRs followed the same pattern (single dose: 97% versus 84%; triple dose: 99.7% versus 96%). Triple-dose regimens outperformed single doses against T. trichiura; three doses of mebendazole - the most efficacious treatment tested - cured 71% (95% CI: 57-82%). Both single and triple doses of either drug were highly efficacious against A. lumbricoides (CR: 93-97%; ERR: all >99.9%). Triple dose regimens cured all Taenia spp. infections, whereas single dose applications cured only half of them. CONCLUSIONS/SIGNIFICANCE: Single-dose oral albendazole is more efficacious against hookworm than mebendazole. To achieve high CRs against both hookworm and T. trichiura, triple dose regimens are warranted. TRIAL REGISTRATION: www.controlled-trials.com ISRCTN47375023. PMID- 21980374 TI - Prenatal cocaine exposure increases synaptic localization of a neuronal RasGEF, GRASP-1 via hyperphosphorylation of AMPAR anchoring protein, GRIP. AB - Prenatal cocaine exposure causes sustained phosphorylation of the synaptic anchoring protein, glutamate receptor interacting protein (GRIP1/2), preventing synaptic targeting of the GluR2/3-containing alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid-type glutamate receptors (AMPARs; J. Neurosci. 29: 6308 6319, 2009). Because overexpression of GRIP-associated neuronal rasGEF protein (GRASP-1) specifically reduces the synaptic targeting of AMPARs, we hypothesized that prenatal cocaine exposure enhances GRASP-1 synaptic membrane localization leading to hyper-activation of ras family proteins and heightened actin polymerization. Our results show a markedly increased GRIP1-associated GRASP-1 content with approximately 40% reduction in its rasGEF activity in frontal cortices (FCX) of 21-day-old (P21) prenatal cocaine-exposed rats. This cocaine effect is the result of a persistent protein kinase C (PKC)- and downstream Src tyrosine kinase-mediated GRIP phosphorylation. The hyperactivated PKC also increased membrane-associated GRASP-1 and activated small G-proteins RhoA, cdc42/Rac1 and Rap1 as well as filamentous actin (F-actin) levels without an effect on the phosphorylation state of actin. Since increased F-actin facilitates protein transport, our results suggest that increased GRASP-1 synaptic localization in prenatal cocaine-exposed brains is an adaptive response to restoring the synaptic expression of AMPA-GluR2/3. Our earlier data demonstrated that persistent PKC-mediated GRIP phosphorylation reduces GluR2/3 synaptic targeting in prenatal cocaine-exposed brains, we now show that the increased GRIP associated GRASP-1 may contribute to the reduction in GluR2/3 synaptic expression and AMPAR signaling defects. PMID- 21980375 TI - HF-EPR, Raman, UV/VIS light spectroscopic, and DFT studies of the ribonucleotide reductase R2 tyrosyl radical from Epstein-Barr virus. AB - Epstein-Barr virus (EBV) belongs to the gamma subfamily of herpes viruses, among the most common pathogenic viruses in humans worldwide. The viral ribonucleotide reductase small subunit (RNR R2) is involved in the biosynthesis of nucleotides, the DNA precursors necessary for viral replication, and is an important drug target for EBV. RNR R2 generates a stable tyrosyl radical required for enzymatic turnover. Here, the electronic and magnetic properties of the tyrosyl radical in EBV R2 have been determined by X-band and high-field/high-frequency electron paramagnetic resonance (EPR) spectroscopy recorded at cryogenic temperatures. The radical exhibits an unusually low g1-tensor component at 2.0080, indicative of a positive charge in the vicinity of the radical. Consistent with these EPR results a relatively high C-O stretching frequency associated with the phenoxyl radical (at 1508 cm-1) is observed with resonance Raman spectroscopy. In contrast to mouse R2, EBV R2 does not show a deuterium shift in the resonance Raman spectra. Thus, the presence of a water molecule as a hydrogen bond donor moiety could not be identified unequivocally. Theoretical simulations showed that a water molecule placed at a distance of 2.6 A from the tyrosyl-oxygen does not result in a detectable deuterium shift in the calculated Raman spectra. UV/VIS light spectroscopic studies with metal chelators and tyrosyl radical scavengers are consistent with a more accessible dimetal binding/radical site and a lower affinity for Fe2+ in EBV R2 than in Escherichia coli R2. Comparison with previous studies of RNR R2s from mouse, bacteria, and herpes viruses, demonstrates that finely tuned electronic properties of the radical exist within the same RNR R2 Ia class. PMID- 21980376 TI - MIQuant--semi-automation of infarct size assessment in models of cardiac ischemic injury. AB - BACKGROUND: The cardiac regenerative potential of newly developed therapies is traditionally evaluated in rodent models of surgically induced myocardial ischemia. A generally accepted key parameter for determining the success of the applied therapy is the infarct size. Although regarded as a gold standard method for infarct size estimation in heart ischemia, histological planimetry is time consuming and highly variable amongst studies. The purpose of this work is to contribute towards the standardization and simplification of infarct size assessment by providing free access to a novel semi-automated software tool. The acronym MIQuant was attributed to this application. METHODOLOGY/PRINCIPAL FINDINGS: Mice were subject to permanent coronary artery ligation and the size of chronic infarcts was estimated by area and midline-length methods using manual planimetry and with MIQuant. Repeatability and reproducibility of MIQuant scores were verified. The validation showed high correlation (r(midline length) = 0.981; r(area) = 0.970 ) and agreement (Bland-Altman analysis), free from bias for midline length and negligible bias of 1.21% to 3.72% for area quantification. Further analysis demonstrated that MIQuant reduced by 4.5-fold the time spent on the analysis and, importantly, MIQuant effectiveness is independent of user proficiency. The results indicate that MIQuant can be regarded as a better alternative to manual measurement. CONCLUSIONS: We conclude that MIQuant is a reliable and an easy-to-use software for infarct size quantification. The widespread use of MIQuant will contribute towards the standardization of infarct size assessment across studies and, therefore, to the systematization of the evaluation of cardiac regenerative potential of emerging therapies. PMID- 21980377 TI - Learning with a network of competing synapses. AB - Competition between synapses arises in some forms of correlation-based plasticity. Here we propose a game theory-inspired model of synaptic interactions whose dynamics is driven by competition between synapses in their weak and strong states, which are characterized by different timescales. The learning of inputs and memory are meaningfully definable in an effective description of networked synaptic populations. We study, numerically and analytically, the dynamic responses of the effective system to various signal types, particularly with reference to an existing empirical motor adaptation model. The dependence of the system-level behavior on the synaptic parameters, and the signal strength, is brought out in a clear manner, thus illuminating issues such as those of optimal performance, and the functional role of multiple timescales. PMID- 21980378 TI - Proteomic analysis of ovarian cancer proximal fluids: validation of elevated peroxiredoxin 1 in patient peripheral circulation. AB - BACKGROUND: Epithelial ovarian cancer (EOC) is the deadliest gynecologic malignancy in the United States. Unfortunately, a validated protein biomarker screening test to detect early stage disease from peripheral blood has not yet been developed. The present investigation assesses the ability to identify tumor relevant proteins from ovarian cancer proximal fluids, including tissue interstitial fluid (TIF) and corresponding ascites, from patients with papillary serous EOC and translates these findings to targeted blood-based immunoassays. METHODOLOGY/PRINCIPAL FINDINGS: Paired TIF and ascites collected from four papillary serous EOC patients at the time of surgery underwent immunodepletion, resolution by 1D gel electrophoresis and in-gel digestion for analysis by liquid chromatography-tandem mass spectrometry, which resulted in an aggregate identification of 569 and 171 proteins from TIF and ascites, respectively. Of these, peroxiredoxin I (PRDX1) was selected for validation in serum by ELISA and demonstrated to be present and significantly elevated (p = 0.0188) in 20 EOC patients with a mean level of 26.0 ng/mL (+/-9.27 SEM) as compared to 4.19 ng/mL (+/-2.58 SEM) from 16 patients with normal/benign ovarian pathology. CONCLUSIONS/SIGNIFICANCE: We have utilized a workflow for harvesting EOC-relevant proximal biofluids, including TIF and ascites, for proteomic analysis. Among the differentially abundant proteins identified from these proximal fluids, PRDX1 was demonstrated to be present in serum and shown by ELISA to be elevated by nearly 6 fold in papillary serous EOC patients relative to normal/benign patients. Our findings demonstrate the facile ability to discover potential EOC-relevant proteins in proximal fluids and confirm their presence in peripheral blood serum. In addition, our finding of elevated levels of PRDX1 in the serum of EOC patients versus normal/benign patients warrants further evaluation as a tumor specific biomarker for EOC. PMID- 21980379 TI - Novel regulation of CCL2 gene expression by murine LITAF and STAT6B. AB - Inflammation is a multifaceted process: beneficial as a defense mechanism but also detrimental depending on its severity and duration. At the site of injury, inflammatory cells are activated by a cascade of mediators, one of which is LITAF, a transcription regulator known to upregulate TNF-alpha. We previously showed that human LITAF forms a complex with human STAT6B, which translocates into the nucleus to upregulate cytokine transcription. To dissect the molecular implications of this complex, a murine model was developed and interactions between mouse STAT6B (mSTAT6B) and mouse LITAF (mLITAF) were analyzed. Both mLITAF and mSTAT6B expression were MyD88- and TLR ligand-dependent. Furthermore, mLITAF was found to mediate LPS-induced CCL2 gene transcription with the cooperation of mSTAT6B leading to CCL2 protein expression. In LITAF-deficient mice, mLITAF-mediated CCL2 production in macrophages was significantly reduced compared to the wild-type control animals. Mice knockdown for mSTAT6B by 6BsiRNA1 tail vein injection resulted in a decrease in serum TNF-alpha and CCL2 production. mLITAF/mSTAT6B complex is proposed to play a role in LPS-induced CCL2 expression and possibly other cytokines. PMID- 21980380 TI - New striatal neurons in a mouse model of progressive striatal degeneration are generated in both the subventricular zone and the striatal parenchyma. AB - Acute striatal lesions increase proliferation in the subventricular zone (SVZ) and induce migration of SVZ neuroblasts to the striatum. However, the potential of these cells to replace acutely degenerated neurons is controversial. The possible contribution of parenchymal progenitors to striatal lesion-induced neurogenesis has been poorly explored. Here, we present a detailed investigation of neurogenesis in the striatum of a mouse model showing slow progressive neurodegeneration of striatal neurons, the Creb1(Camkcre4)Crem-/- mutant mice (CBCM). By using BrdU time course analyses, intraventricular injections of a cell tracker and 3D reconstructions we showed that neurodegeneration in CBCM mice stimulates the migration of SVZ neuroblasts to the striatum without altering SVZ proliferation. SVZ-neuroblasts migrate as chains through the callosal striatal border and then enter within the striatal parenchyma as individual cells. In addition, a population of clustered neuroblasts showing high turnover rates were observed in the mutant striatum that had not migrated from the SVZ. Clustered neuroblasts might originate within the striatum itself because they are specifically associated with parenchymal proliferating cells showing features of intermediate neuronal progenitors such as clustering, expression of EGF receptor and multiple glial (SOX2, SOX9, BLBP) and neuronal (Dlx, Sp8, and to some extent DCX) markers. Newborn striatal neurons had a short lifespan and did not replace projection neurons nor expressed sets of transcription factors involved in their specification. The differentiation failure of endogenous neuroblasts likely occurred cell autonomously because transplanted wild type embryonic precursors correctly differentiated into striatal projection neurons. Thus, we propose that under progressive degeneration, neither SVZ derived nor intra-striatal generated neurons have the potential to differentiate into striatal projection neurons. PMID- 21980381 TI - Apparent temperature and air pollution vs. elderly population mortality in Metro Vancouver. AB - BACKGROUND: Meteorological conditions and air pollution in urban environments have been associated with general population and elderly mortality, showing seasonal variation. OBJECTIVES: This study is designed to evaluate the relationship between apparent temperature (AT) and air pollution (PM2.5) vs. mortality in elderly population of Metro Vancouver. METHODS: Statistical analyses are performed on moving sum daily mortality rates vs. moving average AT and PM2.5 in 1-, 2-, 3-, 5-, and 7-day models for all seasons, warm temperatures above 15 degrees C, and cold temperatures below 10 degrees C. RESULTS: Approximately 37% of the variation in all-season mortality from circulatory and respiratory causes can be explained by the variation in 7-day moving average apparent temperature (r2 = 0.37, p<0.001). Although the analytical results from air pollution models show increasingly better prediction ability of longer time-intervals (r2 = 0.012, p<0.001 in a 7-day model), a very weak negative association between elderly mortality and air pollution is observed. CONCLUSIONS: Apparent temperature is associated with mortality from respiratory and circulatory causes in elderly population of Metro Vancouver. In a changing climate, one may anticipate to observe potential health impacts from the projected high- and particularly from the low-temperature extremes. PMID- 21980382 TI - Dynamical consequences of bandpass feedback loops in a bacterial phosphorelay. AB - Under conditions of nutrient limitation, Bacillus subtilis cells terminally differentiate into a dormant spore state. Progression to sporulation is controlled by a genetic circuit consisting of a phosphorelay embedded in multiple transcriptional feedback loops, which is used to activate the master regulator Spo0A by phosphorylation. These transcriptional regulatory interactions are "bandpass"-like, in the sense that activation occurs within a limited band of Spo0A~P concentrations. Additionally, recent results show that the phosphorelay activation occurs in pulses, in a cell-cycle dependent fashion. However, the impact of these pulsed bandpass interactions on the circuit dynamics preceding sporulation remains unclear. In order to address this question, we measured key features of the bandpass interactions at the single-cell level and analyzed them in the context of a simple mathematical model. The model predicted the emergence of a delayed phase shift between the pulsing activity of the different sporulation genes, as well as the existence of a stable state, with elevated Spo0A activity but no sporulation, embedded within the dynamical structure of the system. To test the model, we used time-lapse fluorescence microscopy to measure dynamics of single cells initiating sporulation. We observed the delayed phase shift emerging during the progression to sporulation, while a re-engineering of the sporulation circuit revealed behavior resembling the predicted additional state. These results show that periodically-driven bandpass feedback loops can give rise to complex dynamics in the progression towards sporulation. PMID- 21980383 TI - Smart skin patterns protect springtails. AB - Springtails, arthropods who live in soil, in decaying material, and on plants, have adapted to demanding conditions by evolving extremely effective and robust anti-adhesive skin patterns. However, details of these unique properties and their structural basis are still unknown. Here we demonstrate that collembolan skin can resist wetting by many organic liquids and at elevated pressures. We show that the combination of bristles and a comb-like hexagonal or rhombic mesh of interconnected nanoscopic granules distinguish the skin of springtails from anti-adhesive plant surfaces. Furthermore, the negative overhang in the profile of the ridges and granules were revealed to be a highly effective, but as yet neglected, design principle of collembolan skin. We suggest an explanation for the non-wetting characteristics of surfaces consisting of such profiles irrespective of the chemical composition. Many valuable opportunities arise from the translation of the described comb-like patterns and overhanging profiles of collembolan skin into man-made surfaces that combine stability against wear and friction with superior non-wetting and anti-adhesive characteristics. PMID- 21980384 TI - Global burden of double malnutrition: has anyone seen it? AB - BACKGROUND: Low- to middle-income countries (LMICs) are believed to be characterized by the coexistence of underweight and overweight. It has also been posited that such coexistence is appearing among the low socioeconomic status (SES) groups. METHODS: We conducted a cross-sectional analysis of nationally representative samples of 451,321 women aged 20-49 years drawn from 57 Demographic and Health Surveys conducted between 1994 and 2008. Body Mass Index (BMI in kg/m2), was used to define underweight and overweight following conventional cut-points. Covariates included age, household wealth, education, and residence. We estimated multinomial multilevel models to assess the extent to which underweight (BMI<18.5 kg/m2) and overweight (BM I>= 25.0 kg/m2) correlate at the country-level, and at the neighborhood-level within each country. RESULTS: In age-adjusted models, there was a strong negative correlation between likelihood of being underweight and overweight at country- (r = -0.79, p<0.001), and at the neighborhood-level within countries (r = -0.51, P<0.001). Negative correlations ranging from -0.11 to -0.90 were observed in 46 of the 57 countries at the neighborhood-level and 29/57 were statistically significant (p <= 0.05). Similar negative correlations were observed in analyses restricted to low SES groups. Finally, the negative correlations across countries, and within countries, appeared to be stable over time in a sub-set of 36 countries. CONCLUSION: The explicitly negative correlations between prevalence of underweight and overweight at the country-level and at neighborhood-level suggest that the hypothesized coexistence of underweight and overweight has not yet occurred in a substantial manner in a majority of LMICs. PMID- 21980385 TI - High-throughput screen for identifying small molecules that target fungal zinc homeostasis. AB - Resistance to traditional antifungal drugs has increased significantly over the past three decades, making identification of novel antifungal agents and new targets an emerging priority. Based on the extraordinary zinc requirement of several fungal pathogens and their well-established sensitivity to zinc deprivation, we developed an efficient cell-based screen to identify new antifungal drugs that target the zinc homeostasis machinery. The screen is based on the zinc-regulated transcription factor Zap1 of Saccharomyces cerevisiae, which regulates transcription of genes like the high-affinity zinc transporter ZRT1. We generated a genetically modified strain of S. cerevisae that reports intracellular zinc deficiency by placing the coding sequence of green fluorescent protein (GFP) under the control of the Zap1-regulated ZRT1 promoter. After showing that the GFP fluorescence signal correlates with low intracellular zinc concentrations in this strain, a protocol was developed for screening small molecule libraries for compounds that induce Zap1-dependent GFP expression. Comparison of control compounds and known modulators of metal metabolism from the library reveals a robust screen (Z' = 0.74) and validates this approach to the discovery of new classes of antifungal compounds that interfere with the intracellular zinc homeostasis. Given that growth of many pathogenic organisms is significantly impaired by zinc limitation; these results identify new types of antifungal drugs that target critical nutrient acquisition pathways. PMID- 21980386 TI - Serological markers suggest heterogeneity of effectiveness of malaria control interventions on Bioko Island, equatorial Guinea. AB - BACKGROUND: In order to control and eliminate malaria, areas of on-going transmission need to be identified and targeted for malaria control interventions. Immediately following intense interventions, malaria transmission can become more heterogeneous if interventions are more successful in some areas than others. Bioko Island, Equatorial Guinea, has been subject to comprehensive malaria control interventions since 2004. This has resulted in substantial reductions in the parasite burden, although this drop has not been uniform across the island. METHODS/PRINCIPAL FINDINGS: In 2008, filter paper blood samples were collected from 7387 people in a cross-sectional study incorporating 18 sentinel sites across Bioko, Equatorial Guinea. Antibodies were measured to P. falciparum Apical Membrane Antigen-1 (AMA-1) by Enzyme Linked Immunosorbent Assay (ELISA). Age-specific seropositivity rates were used to estimate seroconversion rates (SCR). Analysis indicated there had been at least a 60% decline in SCR in four out of five regions on the island. Changes in SCR showed a high degree of congruence with changes in parasite rate (PR) and with regional reductions in all cause child mortality. The mean age adjusted concentration of anti-AMA-1 antibodies was mapped to identify areas where individual antibody responses were higher than expected. This approach confirmed the North West of the island as a major focus of continuing infection and an area where control interventions need to be concentrated or re-evaluated. CONCLUSION/INTERPRETATION: Both SCR and PR revealed heterogeneity in malaria transmission and demonstrated the variable effectiveness of malaria control measures. This work confirms the utility of serological analysis as an adjunct measure for monitoring transmission. Age specific seroprevalence based evidence of changes in transmission over time will be of particular value when no baseline data are available. Importantly, SCR data provide additional evidence to link malaria control activities to contemporaneous reductions in all-cause child mortality. PMID- 21980387 TI - Effect of folic acid supplementation on cardiovascular outcomes: a systematic review and meta-analysis. AB - BACKGROUND: Folic acid is widely used to lower homocysteine concentrations and prevent adverse cardiovascular outcomes. However, the effect of folic acid on cardiovascular events is not clear at the present time. We carried out a comprehensive systematic review and meta-analysis to assess the effects of folic acid supplementation on cardiovascular outcomes. METHODOLOGY AND PRINCIPAL FINDINGS: We systematically searched Medline, EmBase, the Cochrane Central Register of Controlled Trials, reference lists of articles, and proceedings of major meetings for relevant literature. We included randomized placebo-controlled trials that reported on the effects of folic acid on cardiovascular events compared to placebo. Of 1594 identified studies, we included 16 trials reporting data on 44841 patients. These studies reported 8238 major cardiovascular events, 2001 strokes, 2917 myocardial infarctions, and 6314 deaths. Folic acid supplementation as compared to placebo had no effect on major cardiovascular events (RR, 0.98; 95% CI, 0.93-1.04), stroke (RR, 0.89; 95% CI,0.78-1.01), myocardial infarction (RR, 1.00; 95% CI, 0.93-1.07), or deaths from any cause (RR, 1.00;95% CI, 0.96-1.05). Moreover, folic acid as compared to placebo also had no effect on the following secondary outcomes: risk of revascularization (RR, 1.05; 95%CI, 0.95-1.16), acute coronary syndrome (RR, 1.06; 95%CI, 0.97-1.15), cancer (RR, 1.08; 95%CI, 0.98-1.21), vascular death (RR, 0.94; 95%CI,0.88-1.02), or non-vascular death (RR, 1.06; 95%CI, 0.97-1.15). CONCLUSION/SIGNIFICANCE: Folic acid supplementation does not effect on the incidence of major cardiovascular events, stroke, myocardial infarction or all cause mortality. PMID- 21980388 TI - Abeta peptide fibrillar architectures controlled by conformational constraints of the monomer. AB - Anomalous self-assembly of the Abeta peptide into fibrillar amyloid deposits is strongly correlated with the development of Alzheimer's disease. Abeta fibril extension follows a template guided "dock and lock" mechanism where polymerisation is catalysed by the fibrillar ends. Using surface plasmon resonance (SPR) and quenched hydrogen-deuterium exchange NMR (H/D-exchange NMR), we have analysed the fibrillar structure and polymerisation properties of both the highly aggregation prone Abeta1-40 Glu22Gly (Abeta(40Arc)) and wild type Abeta1-40 (Abeta(40WT)). The solvent protection patterns from H/D exchange experiments suggest very similar structures of the fibrillar forms. However, through cross-seeding experiments monitored by SPR, we found that the monomeric form of Abeta(40WT) is significantly impaired to acquire the fibrillar architecture of Abeta(40Arc). A detailed characterisation demonstrated that Abeta(40WT) has a restricted ability to dock and isomerise with high binding affinity onto Abeta(40Arc) fibrils. These results have general implications for the process of fibril assembly, where the rate of polymerisation, and consequently the architecture of the formed fibrils, is restricted by conformational constraints of the monomers. Interestingly, we also found that the kinetic rate of fibril formation rather than the thermodynamically lowest energy state determines the overall fibrillar structure. PMID- 21980389 TI - Tumor site immune markers associated with risk for subsequent basal cell carcinomas. AB - BACKGROUND: Basal cell carcinoma (BCC) tumors are the most common skin cancer and are highly immunogenic. OBJECTIVE: The goal of this study was to assess how immune-cell related gene expression in an initial BCC tumor biopsy was related to the appearance of subsequent BCC tumors. MATERIALS AND METHODS: Levels of mRNA for CD3epsilon (a T-cell receptor marker), CD25 (the alpha chain of the interleukin (IL)-2 receptor expressed on activated T-cells and B-cells), CD68 (a marker for monocytes/macrophages), the cell surface glycoprotein intercellular adhesion molecule-1 (ICAM-1), the cytokine interferon-gamma (IFN-gamma) and the anti-inflammatory cytokine IL-10 were measured in BCC tumor biopsies from 138 patients using real-time PCR. RESULTS: The median follow-up was 26.6 months, and 61% of subjects were free of new BCCs two years post-initial biopsy. Patients with low CD3epsilon CD25, CD68, and ICAM-1 mRNA levels had significantly shorter times before new tumors were detected (p = 0.03, p = 0.02, p = 0.003, and p = 0.08, respectively). Furthermore, older age diminished the association of mRNA levels with the appearance of subsequent tumors. CONCLUSIONS: Our results show that levels of CD3epsilon, CD25, CD68, and ICAM-1 mRNA in BCC biopsies may predict risk for new BCC tumors. PMID- 21980390 TI - Resveratrol inhibits growth of orthotopic pancreatic tumors through activation of FOXO transcription factors. AB - BACKGROUND: The forkhead transcription factors of the O class (FOXO) play a direct role in cellular proliferation, oxidative stress response, and tumorigenesis. The objectives of this study were to examine whether FOXOs regulate antitumor activities of resveratrol in pancreatic cancer cells in vitro and in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Pancreatic cancer cell lines were treated with resveratrol. Cell viability, colony formation, apoptosis and cell cycle were measured by XTT, soft agar, TUNEL and flow cytometry assays, respectively. FOXO nuclear translocation, DNA binding and transcriptional activities were measured by fluorescence technique, gelshift and luciferase assay, respectively. Mice were orthotopically implanted with PANC1 cells and orally gavaged with resveratrol. The components of PI3K and ERK pathways, FOXOs and their target gene expressions were measured by the Western blot analysis. Resveratrol inhibited cell viability and colony formations, and induced apoptosis through caspase-3 activation in four pancreatic cancer cell lines (PANC-1, MIA PaCa-2, Hs766T, and AsPC-1). Resveratrol induced cell cycle arrest by up regulating the expression of p21/CIP1, p27/KIP1 and inhibiting the expression of cyclin D1. Resveratrol induced apoptosis by up-regulating Bim and activating caspase-3. Resveratrol inhibited phosphorylation of FOXOs, and enhanced their nuclear translocation, FOXO-DNA binding and transcriptional activities. The inhibition of PI3K/AKT and MEK/ERK pathways induced FOXO transcriptional activity and apoptosis. Furthermore, deletion of FOXO genes abrogated resveratrol-induced cell cycle arrest and apoptosis. Finally, resveratrol-treated mice showed significant inhibition in tumor growth which was associated with reduced phosphorylation of ERK, PI3K, AKT, FOXO1 and FOXO3a, and induction of apoptosis and FOXO target genes. CONCLUSIONS: These data suggest that inhibition of ERK and AKT pathways act together to activate FOXO transcription factors which are involved in resveratrol-mediated pancreatic tumor growth suppression. PMID- 21980391 TI - TGF-beta regulates DNA methyltransferase expression in prostate cancer, correlates with aggressive capabilities, and predicts disease recurrence. AB - BACKGROUND: DNA methyltransferase (DNMT) is one of the major factors mediating the methylation of cancer related genes such as TGF-beta receptors (TbetaRs). This in turn may result in a loss of sensitivity to physiologic levels of TGF beta in aggressive prostate cancer (CaP). The specific mechanisms of DNMT's role in CaP remain undetermined. In this study, we describe the mechanism of TGF-beta mediated DNMT in CaP and its association with clinical outcomes following radical prostatectomy. METHODOLOGY/PRINCIPAL FINDINGS: We used human CaP cell lines with varying degrees of invasive capability to describe how TGF-beta mediates the expression of DNMT in CaP, and its effects on methylation status of TGF-beta receptors and the invasive capability of CaP in vitro and in vivo. Furthermore, we determined the association between DNMT expression and clinical outcome after radical prostatectomy. We found that more aggressive CaP cells had significantly higher TGF-beta levels, increased expression of DNMT, but reduced TbetaRs when compared to benign prostate cells and less aggressive prostate cancer cells. Blockade of TGF-beta signaling or ERK activation (p-ERK) was associated with a dramatic decrease in the expression of DNMT, which results in a coincident increase in the expression of TbetaRs. Blockade of either TGF-beta signaling or DNMT dramatically decreased the invasive capabilities of CaP. Inhibition of TGF beta in an TRAMP-C2 CaP model in C57BL/6 mice using 1D11 was associated with downregulation of DNMTs and p-ERK and impairment in tumor growth. Finally, independent of Gleason grade, increased DNMT1 expression was associated with biochemical recurrence following surgical treatment for prostate cancer. CONCLUSIONS AND SIGNIFICANCE: Our findings demonstrate that CaP derived TGF-beta may induce the expression of DNMTs in CaP which is associated with methylation of its receptors and the aggressive potential of CaP. In addition, DNMTs is an independent predictor for disease recurrence after prostatectomy, and may have clinical implications for CaP prognostication and therapy. PMID- 21980392 TI - Bone marrow derived mesenchymal stem cells inhibit inflammation and preserve vascular endothelial integrity in the lungs after hemorrhagic shock. AB - Hemorrhagic shock (HS) and trauma is currently the leading cause of death in young adults worldwide. Morbidity and mortality after HS and trauma is often the result of multi-organ failure such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), conditions with few therapeutic options. Bone marrow derived mesenchymal stem cells (MSCs) are a multipotent stem cell population that has shown therapeutic promise in numerous pre-clinical and clinical models of disease. In this paper, in vitro studies with pulmonary endothelial cells (PECs) reveal that conditioned media (CM) from MSCs and MSC-PEC co-cultures inhibits PEC permeability by preserving adherens junctions (VE cadherin and beta-catenin). Leukocyte adhesion and adhesion molecule expression (VCAM-1 and ICAM-1) are inhibited in PECs treated with CM from MSC-PEC co cultures. Further support for the modulatory effects of MSCs on pulmonary endothelial function and inflammation is demonstrated in our in vivo studies on HS in the rat. In a rat "fixed volume" model of mild HS, we show that MSCs administered IV potently inhibit systemic levels of inflammatory cytokines and chemokines in the serum of treated animals. In vivo MSCs also inhibit pulmonary endothelial permeability and lung edema with concurrent preservation of the vascular endothelial barrier proteins: VE-cadherin, Claudin-1, and Occludin-1. Leukocyte infiltrates (CD68 and MPO positive cells) are also decreased in lungs with MSC treatment. Taken together, these data suggest that MSCs, acting directly and through soluble factors, are potent stabilizers of the vascular endothelium and inflammation. These data are the first to demonstrate the therapeutic potential of MSCs in HS and have implications for the potential use of MSCs as a cellular therapy in HS-induced lung injury. PMID- 21980394 TI - Does lateral transmission obscure inheritance in hunter-gatherer languages? AB - In recent years, linguists have begun to increasingly rely on quantitative phylogenetic approaches to examine language evolution. Some linguists have questioned the suitability of phylogenetic approaches on the grounds that linguistic evolution is largely reticulate due to extensive lateral transmission, or borrowing, among languages. The problem may be particularly pronounced in hunter-gatherer languages, where the conventional wisdom among many linguists is that lexical borrowing rates are so high that tree building approaches cannot provide meaningful insights into evolutionary processes. However, this claim has never been systematically evaluated, in large part because suitable data were unavailable. In addition, little is known about the subsistence, demographic, ecological, and social factors that might mediate variation in rates of borrowing among languages. Here, we evaluate these claims with a large sample of hunter gatherer languages from three regions around the world. In this study, a list of 204 basic vocabulary items was collected for 122 hunter-gatherer and small-scale cultivator languages from three ecologically diverse case study areas: northern Australia, northwest Amazonia, and California and the Great Basin. Words were rigorously coded for etymological (inheritance) status, and loan rates were calculated. Loan rate variability was examined with respect to language area, subsistence mode, and population size, density, and mobility; these results were then compared to the sample of 41 primarily agriculturalist languages. Though loan levels varied both within and among regions, they were generally low in all regions (mean 5.06%, median 2.49%, and SD 7.56), despite substantial demographic, ecological, and social variation. Amazonian levels were uniformly very low, with no language exhibiting more than 4%. Rates were low but more variable in the other two study regions, in part because of several outlier languages where rates of borrowing were especially high. High mobility, prestige asymmetries, and language shift may contribute to the high rates in these outliers. No support was found for claims that hunter-gatherer languages borrow more than agriculturalist languages. These results debunk the myth of high borrowing in hunter-gatherer languages and suggest that the evolution of these languages is governed by the same type of rules as those operating in large-scale agriculturalist speech communities. The results also show that local factors are likely to be more critical than general processes in determining high (or low) loan rates. PMID- 21980393 TI - Hypertonic stress induces VEGF production in human colon cancer cell line Caco-2: inhibitory role of autocrine PGE2. AB - Vascular Endothelial Growth Factor (VEGF) is a major regulator of angiogenesis. VEGF expression is up regulated in response to micro-environmental cues related to poor blood supply such as hypoxia. However, regulation of VEGF expression in cancer cells is not limited to the stress response due to increased volume of the tumor mass. Lipid mediators in particular arachidonic acid-derived prostaglandin (PG)E2 are regulators of VEGF expression and angiogenesis in colon cancer. In addition, increased osmolarity that is generated during colonic water absorption and feces consolidation seems to activate colon cancer cells and promote PGE2 generation. Such physiological stimulation may provide signaling for cancer promotion. Here we investigated the effect of exposure to a hypertonic medium, to emulate colonic environment, on VEGF production by colon cancer cells. The role of concomitant PGE2 generation and MAPK activation was addressed by specific pharmacological inhibition. Human colon cancer cell line Caco-2 exposed to a hypertonic environment responded with marked VEGF and PGE2 production. VEGF production was inhibited by selective inhibitors of ERK 1/2 and p38 MAPK pathways. To address the regulatory role of PGE2 on VEGF production, Caco-2 cells were treated with cPLA2 (ATK) and COX-2 (NS-398) inhibitors, that completely block PGE2 generation. The Caco-2 cells were also treated with a non selective PGE2 receptor antagonist. Each treatment significantly increased the hypertonic stress-induced VEGF production. Moreover, addition of PGE2 or selective EP2 receptor agonist to activated Caco-2 cells inhibited VEGF production. The autocrine inhibitory role for PGE2 appears to be selective to hypertonic environment since VEGF production induced by exposure to CoCl2 was decreased by inhibition of concomitant PGE2 generation. Our results indicated that hypertonicity stimulates VEGF production in colon cancer cell lines. Also PGE2 plays an inhibitory role on VEGF production by Caco-2 cells exposed to hyperosmotic stress through EP2 activation. PMID- 21980396 TI - How objects are grasped: the interplay between affordances and end-goals. AB - BACKGROUND: Substantial literature has demonstrated that how the hand approaches an object depends on the manipulative action that will follow object contact. Little is known about how the placement of individual fingers on objects is affected by the end-goal of the action. METHODOLOGY/PRINCIPAL FINDINGS: Hand movement kinematics were measured during reaching for and grasping movements towards two objects (stimuli): a bottle with an ordinary cylindrical shape and a bottle with a concave constriction. The effects of the stimuli's weight (half full or completely full of water) and the end-goals (pouring, moving) of the action were also assessed. Analysis of key kinematic landmarks measured during reaching movements indicate that object affordance facilitates the end-goal of the action regardless of accuracy constraints. Furthermore, the placement of individual digits at contact is modulated by the shape of the object and the end goal of the action. CONCLUSIONS/SIGNIFICANCE: These findings offer a substantial contribution to the current debate about the role played by affordances and end goals in determining the structure of reach-to-grasp movements. PMID- 21980395 TI - The effect of OPA1 on mitochondrial Ca2+ signaling. AB - The dynamin-related GTPase protein OPA1, localized in the intermembrane space and tethered to the inner membrane of mitochondria, participates in the fusion of these organelles. Its mutation is the most prevalent cause of Autosomal Dominant Optic Atrophy. OPA1 controls the diameter of the junctions between the boundary part of the inner membrane and the membrane of cristae and reduces the diffusibility of cytochrome c through these junctions. We postulated that if significant Ca2+ uptake into the matrix occurs from the lumen of the cristae, reduced expression of OPA1 would increase the access of Ca2+ to the transporters in the crista membrane and thus would enhance Ca2+ uptake. In intact H295R adrenocortical and HeLa cells cytosolic Ca2+ signals evoked with K+ and histamine, respectively, were transferred into the mitochondria. The rate and amplitude of mitochondrial [Ca2+] rise (followed with confocal laser scanning microscopy and FRET measurements with fluorescent wide-field microscopy) were increased after knockdown of OPA1, as compared with cells transfected with control RNA or mitofusin1 siRNA. Ca2+ uptake was enhanced despite reduced mitochondrial membrane potential. In permeabilized cells the rate of Ca2+ uptake by depolarized mitochondria was also increased in OPA1-silenced cells. The participation of Na+/Ca2+ and Ca2+/H+ antiporters in this transport process is indicated by pharmacological data. Altogether, our observations reveal the significance of OPA1 in the control of mitochondrial Ca2+ metabolism. PMID- 21980397 TI - Fructose modulates cardiomyocyte excitation-contraction coupling and Ca2+ handling in vitro. AB - BACKGROUND: High dietary fructose has structural and metabolic cardiac impact, but the potential for fructose to exert direct myocardial action is uncertain. Cardiomyocyte functional responsiveness to fructose, and capacity to transport fructose has not been previously demonstrated. OBJECTIVE: The aim of the present study was to seek evidence of fructose-induced modulation of cardiomyocyte excitation-contraction coupling in an acute, in vitro setting. METHODS AND RESULTS: The functional effects of fructose on isolated adult rat cardiomyocyte contractility and Ca2+ handling were evaluated under physiological conditions (37 degrees C, 2 mM Ca2+, HEPES buffer, 4 Hz stimulation) using video edge detection and microfluorimetry (Fura2) methods. Compared with control glucose (11 mM) superfusate, 2-deoxyglucose (2 DG, 11 mM) substitution prolonged both the contraction and relaxation phases of the twitch (by 16 and 36% respectively, p<0.05) and this effect was completely abrogated with fructose supplementation (11 mM). Similarly, fructose prevented the Ca2+ transient delay induced by exposure to 2 DG (time to peak Ca2+ transient: 2 DG: 29.0+/-2.1 ms vs. glucose: 23.6+/-1.1 ms vs. fructose +2 DG: 23.7+/-1.0 ms; p<0.05). The presence of the fructose transporter, GLUT5 (Slc2a5) was demonstrated in ventricular cardiomyocytes using real time RT-PCR and this was confirmed by conventional RT PCR. CONCLUSION: This is the first demonstration of an acute influence of fructose on cardiomyocyte excitation-contraction coupling. The findings indicate cardiomyocyte capacity to transport and functionally utilize exogenously supplied fructose. This study provides the impetus for future research directed towards characterizing myocardial fructose metabolism and understanding how long term high fructose intake may contribute to modulating cardiac function. PMID- 21980398 TI - Negative regulation of C/EBPbeta1 by sumoylation in breast cancer cells. AB - Sumoylation is a post-translational modification that is oftentimes deregulated in diseases such as cancer. Transcription factors are frequent targets of sumoylation and modification by SUMO can affect subcellular localization, transcriptional activity, and stability of the target protein. C/EBPbeta1 is one such transcription factor that is modified by SUMO-2/3. Non-sumoylated C/EBPbeta1, p52-C/EBPbeta1, is expressed in normal mammary epithelial cells but not breast cancer cell lines and plays a role in oncogene-induced senescence, a tumor suppressive mechanism. Although p52-C/EBPbeta1 is not observed via immunoblot in breast cancer cell lines, higher molecular weight bands are observed when breast cancer cell lines are subjected to immunoblot analysis with a C/EBPbeta1-specific antibody. We show that exogenously expressed C/EBPbeta1 is sumoylated in breast cancer cells, and that the higher molecular weight bands we observe in anti-C/EBPbeta1 immunoblots of breast cancer cell lines is sumoylated C/EBPbeta1. Phosphorylation oftentimes enhances sumoylation, and phosphorylation cascades are activated in breast cancer cells. We demonstrate that phosphorylation of C/EBPbeta1Thr235 by Erk-2 enhances sumoylation of C/EBPbeta1 in vitro. In addition, sumoylated C/EBPbeta1 is phosphorylated on Thr235 and mutation of Thr235 to alanine leads to a decrease in sumoylation of C/EBPbeta1. Finally, using a C/EBPbeta1-SUMO fusion protein we show that constitutive sumoylation of C/EBPbeta1 completely blocks its capability to induce senescence in WI38 fibroblasts expressing hTERT. Thus, sumolylation of C/EBPbeta1 in breast cancer cells may be a mechanism to circumvent oncogene-induced senescence. PMID- 21980399 TI - In vivo induction of oocyte maturation and ovulation in zebrafish. AB - The maturation of fish oocytes is a well-characterized system induced by progestins via non-genomic actions. In a previous study, we demonstrated that diethylstilbestrol (DES), a non-steroidal estrogen, induces fish oocyte maturation via the membrane progestin receptor (mPR). Here, we attempted to evaluate the effect of DES as an environmental endocrine disrupting chemical (EDC) upon fish oocyte maturation using live zebrafish. DES triggered oocyte maturation within several hours in vivo when administrated directly into the surrounding water. The natural teleost maturation-inducing hormone, 17alpha, 20beta-dihydroxy-4-pregnen-3-one (17,20beta-DHP) also induced oocyte maturation in vivo. Steroids such as testosterone, progesterone or 17alpha hydroxyprogesterone were also effective in vivo. Further studies indicated that externally applied 17,20beta-DHP even induced ovulation. In contrast to 17,20beta -DHP, DES induced maturation but not ovulation. Theoretically this assay system provides a means to distinguish pathways involved in the induction of ovulation, which are known to be induced by genomic actions from the pathway normally involved in the induction of oocyte maturation, a typical non-genomic action dependent pathway. In summary, we have demonstrated the effect of EDCs on fish oocyte maturation in vivo. To address the effects, we have explored a conceptually new approach to distinguish between the genomic and non-genomic actions induced by steroids. The assay can be applied to screens of progestin like effects upon oocyte maturation and ovulation for small molecules of pharmacological agents or EDCs. PMID- 21980400 TI - PI3K and ERK-induced Rac1 activation mediates hypoxia-induced HIF-1alpha expression in MCF-7 breast cancer cells. AB - BACKGROUND: Hypoxia-inducible factor 1 (HIF-1alpha) expression induced by hypoxia plays a critical role in promoting tumor angiogenesis and metastasis. However, the molecular mechanisms underlying the induction of HIF-1alpha in tumor cells remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we reported that hypoxia could induce HIF-1alpha and VEGF expression accompanied by Rac1 activation in MCF-7 breast cancer cells. Blockade of Rac1 activation with ectopic expression of an inactive mutant form of Rac1 (T17N) or Rac1 siRNA downregulated hypoxia-induced HIF-1alpha and VEGF expression. Furthermore, Hypoxia increased PI3K and ERK signaling activity. Both PI3K inhibitor LY294002 and ERK inhibitor U0126 suppressed hypoxia-induced Rac1 activation as well as HIF-1alpha expression. Moreover, hypoxia treatment resulted in a remarkable production of reactive oxygen species (ROS). N-acetyl-L-cysteine, a scavenger of ROS, inhibited hypoxia-induced ROS generation, PI3K, ERK and Rac1 activation as well as HIF 1alpha expression. CONCLUSIONS/SIGNIFICANCE: Taken together, our study demonstrated that hypoxia-induced HIF-1alpha expression involves a cascade of signaling events including ROS generation, activation of PI3K and ERK signaling, and subsequent activation of Rac1. PMID- 21980401 TI - Tmem26 is dynamically expressed during palate and limb development but is not required for embryonic survival. AB - The Tmem26 gene encodes a novel protein that we have previously shown to be regulated by hedgehog signalling in the mouse limb. We now report that Tmem26 expression is spatially and temporally restricted in other regions of the mouse embryo, most notably the facial primordia. In particular, Tmem26 expression in the mesenchyme of the maxillary and nasal prominences is coincident with fusion of the primary palate. In the secondary palate, Tmem26 is expressed in the palatal shelves during their growth and fusion but is downregulated once fusion is complete. Expression was also detected at the midline of the expanding mandible and at the tips of the eyelids as they migrate across the cornea. Given the spatio-temporally restricted expression of Tmem26, we sought to uncover a functional role in embryonic development through targeted gene inactivation in the mouse. However, ubiquitous inactivation of Tmem26 led to no overt phenotype in the resulting embryos or adult mice, suggesting that TMEM26 function is dispensable for embryonic survival. PMID- 21980402 TI - Immunogenic Eimeria tenella glycosylphosphatidylinositol-anchored surface antigens (SAGs) induce inflammatory responses in avian macrophages. AB - BACKGROUND: At least 19 glycosylphosphatidylinositol (GPI)-anchored surface antigens (SAGs) are expressed specifically by second-generation merozoites of Eimeria tenella, but the ability of these proteins to stimulate immune responses in the chicken is unknown. METHODOLOGY/PRINCIPAL FINDINGS: Ten SAGs, belonging to two previously defined multigene families (A and B), were expressed as soluble recombinant (r) fusion proteins in E. coli. Chicken macrophages were treated with purified rSAGs and changes in macrophage nitrite production, and in mRNA expression profiles of inducible nitric oxide synthase (iNOS) and of a panel of cytokines were measured. Treatment with rSAGs 4, 5, and 12 induced high levels of macrophage nitric oxide production and IL-1beta mRNA transcription that may contribute to the inflammatory response observed during E. tenella infection. Concomitantly, treatment with rSAGs 4, 5 and 12 suppressed the expression of IL 12 and IFN-gamma and elevated that of IL-10, suggesting that during infection these molecules may specifically impair the development of cellular mediated immunity. CONCLUSIONS/SIGNIFICANCE: In summary, some E. tenella SAGs appear to differentially modulate chicken innate and humoral immune responses and those derived from multigene family A (especially rSAG 12) may be more strongly linked with E. tenella pathogenicity associated with the endogenous second generation stages. PMID- 21980404 TI - Twinning across the Developing World. AB - BACKGROUND: Until now, little was known about the variation in incidence of twin births across developing countries, because national representative data was lacking. This study provides the first comprehensive overview of national twinning rates across the developing world on the basis of reliable survey data. METHODS: Data on incidence of twinning was extracted from birth histories of women aged 15-49 interviewed in 150 Demographic and Health Surveys, held between 1987 and 2010 in 75 low and middle income countries. During the interview, information on all live births experienced by the women was recorded, including whether it was a singleton or multiple birth. Information was available for 2.47 million births experienced by 1.38 million women in a period of ten years before the interview. Twinning incidence was measured as the number of twin births per thousand births. Data for China were computed on the basis of published figures from the 1990 census. Both natural and age-standardized twinning rates are presented. RESULTS/CONCLUSIONS: The very low natural twinning rates of 6-9 per thousand births previously observed in some East Asian countries turn out to be the dominant pattern in the whole South and South-East Asian region. Very high twinning rates of above 18 per thousand are not restricted to Nigeria (until now seen as the world's twinning champion) but found in most Central-African countries. Twinning rates in Latin America turn out to be as low as those in Asia. Changes over time are small and not in a specific direction. SIGNIFICANCE: We provide the most complete and comparable overview of twinning rates across the developing world currently possible. PMID- 21980403 TI - The histone demethylase Jarid1b (Kdm5b) is a novel component of the Rb pathway and associates with E2f-target genes in MEFs during senescence. AB - Senescence is a robust cell cycle arrest controlled by the p53 and Rb pathways that acts as an important barrier to tumorigenesis. Senescence is associated with profound alterations in gene expression, including stable suppression of E2f target genes by heterochromatin formation. Some of these changes in chromatin composition are orchestrated by Rb. In complex with E2f, Rb recruits chromatin modifying enzymes to E2f target genes, leading to their transcriptional repression. To identify novel chromatin remodeling enzymes that specifically function in the Rb pathway, we used a functional genetic screening model for bypass of senescence in murine cells. We identified the H3K4-demethylase Jarid1b as novel component of the Rb pathway in this screening model. We find that depletion of Jarid1b phenocopies knockdown of Rb1 and that Jarid1b associates with E2f-target genes during cellular senescence. These results suggest a role for Jarid1b in Rb-mediated repression of cell cycle genes during senescence. PMID- 21980405 TI - A hypomethylating variant of MTHFR, 677C>T, blunts the neural response to errors in patients with schizophrenia and healthy individuals. AB - BACKGROUND: Responding to errors is a critical first step in learning from mistakes, a process that is abnormal in schizophrenia. To gain insight into the neural and molecular mechanisms of error processing, we used functional MRI to examine effects of a genetic variant in methylenetetrahydrofolate reductase (MTHFR 677C>T, rs1801133) that increases risk for schizophrenia and that has been specifically associated with increased perseverative errors among patients. MTHFR is a key regulator of the intracellular one-carbon milieu, including DNA methylation, and each copy of the 677T allele reduces MTHFR activity by 35%. METHODOLOGY/PRINCIPAL FINDINGS: Using an antisaccade paradigm, we found that the 677T allele induces a dose-dependent blunting of dorsal anterior cingulate cortex (dACC) activation in response to errors, a pattern that was identical in healthy individuals and patients with schizophrenia. Further, the normal relationship between dACC activation and error rate was disrupted among carriers of the 677T allele. CONCLUSIONS/SIGNIFICANCE: These findings implicate an epigenetic mechanism in the neural response to errors, and provide insight into normal cognitive variation through a schizophrenia risk gene. PMID- 21980406 TI - Birthweight, maternal weight trajectories and global DNA methylation of LINE-1 repetitive elements. AB - Low birthweight, premature birth, intrauterine growth retardation, and maternal malnutrition have been related to an increased risk of cardiovascular disease, type 2 diabetes mellitus, obesity, and neuropsychiatric disorders later in life. Conversely, high birthweight has been linked to future risk of cancer. Global DNA methylation estimated by the methylation of repetitive sequences in the genome is an indicator of susceptibility to chronic diseases. We used data and biospecimens from an epigenetic birth cohort to explore the association between trajectories of fetal and maternal weight and LINE-1 methylation in 319 mother-child dyads. Newborns with low or high birthweight had significantly lower LINE-1 methylation levels in their cord blood compared to normal weight infants after adjusting for gestational age, sex of the child, maternal age at delivery, and maternal smoking during pregnancy (p = 0.007 and p = 0.036, respectively), but the magnitude of the difference was small. Infants born prematurely also had lower LINE-1 methylation levels in cord blood compared to term infants, and this difference, though small, was statistically significant (p = 0.004). We did not find important associations between maternal prepregnancy BMI or gestational weight gain and global methylation of the cord blood or fetal placental tissue. In conclusion, we found significant differences in cord blood LINE-1 methylation among newborns with low and high birthweight as well as among prematurely born infants. Future studies may elucidate whether chromosomal instabilities or other functional consequences of these changes contribute to the increased risk of chronic diseases among individuals with these characteristics. PMID- 21980407 TI - Early hypothalamic FTO overexpression in response to maternal obesity--potential contribution to postweaning hyperphagia. AB - BACKGROUND: Intrauterine and postnatal overnutrition program hyperphagia, adiposity and glucose intolerance in offspring. Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene have been linked to increased risk of obesity. FTO is highly expressed in hypothalamic regions critical for energy balance and hyperphagic phenotypes were linked with FTO SNPs. As nutrition during fetal development can influence the expression of genes involved in metabolic function, we investigated the impact of maternal obesity on FTO. METHODS: Female Sprague Dawley rats were exposed to chow or high fat diet (HFD) for 5 weeks before mating, throughout gestation and lactation. On postnatal day 1 (PND1), some litters were adjusted to 3 pups (vs. 12 control) to induce postnatal overnutrition. At PND20, rats were weaned onto chow or HFD for 15 weeks. FTO mRNA expression in the hypothalamus and liver, as well as hepatic markers of lipid metabolism were measured. RESULTS: At weaning, hypothalamic FTO mRNA expression was increased significantly in offspring of obese mothers and FTO was correlated with both visceral and epididymal fat mass (P<0.05); body weight approached significance (P = 0.07). Hepatic FTO and Fatty Acid Synthase mRNA expression were decreased by maternal obesity. At 18 weeks, FTO mRNA expression did not differ between groups; however body weight was significantly correlated with hypothalamic FTO. Postnatal HFD feeding significantly reduced hepatic Carnitine Palmitoyltransferase-1a but did not affect the expression of other hepatic markers investigated. FTO was not affected by chronic HFD feeding. SIGNIFICANCE: Maternal obesity significantly impacted FTO expression in both hypothalamus and liver at weaning. Early overexpression of hypothalamic FTO correlated with increased adiposity and later food intake of siblings exposed to HFD suggesting upregulation of FTO may contribute to subsequent hyperphagia, in line with some human data. No effect of maternal obesity was observed on FTO in adulthood. PMID- 21980408 TI - The novel gamma secretase inhibitor RO4929097 reduces the tumor initiating potential of melanoma. AB - Several reports have demonstrated a role for aberrant NOTCH signaling in melanoma genesis and progression, prompting us to explore if targeting this pathway is a valid therapeutic approach against melanoma. We targeted NOTCH signaling using RO4929097, a novel inhibitor of gamma secretase, which is a key component of the enzymatic complex that cleaves and activates NOTCH. The effects of RO4929097 on the oncogenic and stem cell properties of a panel of melanoma cell lines were tested both in vitro and in vivo, using xenograft models. In human primary melanoma cell lines, RO4929097 decreased the levels of NOTCH transcriptional target HES1. This was accompanied by reduced proliferation and impaired ability to form colonies in soft agar and to organize in tridimensional spheres. Moreover, RO4929097 affected the growth of human primary melanoma xenograft in NOD/SCID/IL2gammaR-/- mice and inhibited subsequent tumor formation in a serial xenotransplantation model, suggesting that inhibition of NOTCH signaling suppresses the tumor initiating potential of melanoma cells. In addition, RO4929097 decreased tumor volume and blocked the invasive growth pattern of metastatic melanoma cell lines in vivo. Finally, increased gene expression of NOTCH signaling components correlated with shorter post recurrence survival in metastatic melanoma cases. Our data support NOTCH inhibition as a promising therapeutic strategy against melanoma. PMID- 21980409 TI - Identification and characterization of a novel multipotent sub-population of Sca 1+ cardiac progenitor cells for myocardial regeneration. AB - METHODS AND RESULTS: The cardiac stem/progenitor cells from adult mice were seeded at low density in serum-free medium. The colonies thus obtained were expanded separately and assessed for expression of stem cell antigen-1 (Sca-1). Two colonies each with high Sca-1 (CSH1; 95.9%; CSH2; 90.6%) and low Sca-1 (CSL1; 37.1%; CSL2; 17.4%) expressing cells were selected for further studies. Sca-1+ cells (98.4%) isolated using Magnetic Cell Sorting System (MACS) from the hearts were used as a control. Although the selected populations were similar in surface marker expression (low in c-kit, CD45, CD34, CD31 and high in CD29), these cells exhibited diverse differentiation potential. Unlike CSH1, CSH2 expressed Nanog, TERT, Bcrp1, Nestin, Musashi1 and Isl-1, and also showed differentiation into osteogenic, chondrogenic, smooth muscle, endothelial and cardiac lineages. MACS sorted cells exhibited similar tendency albeit with relatively weaker differentiation potential. Transplantation of CSH2 cells into infarcted heart showed attenuated infarction size, significantly preserved left ventricular function and anterior wall thickness, and increased capillary density. We also observed direct differentiation of transplanted cells into endothelium and cardiomyocytes. CONCLUSIONS: The cardiac stem/progenitor cells isolated by a combined clonal selection and surface marker approach possessed multiple stem cell features important for cardiac regeneration. PMID- 21980410 TI - Composition influences the pathway but not the outcome of the metabolic response of bacterioplankton to resource shifts. AB - Bacterioplankton community metabolism is central to the functioning of aquatic ecosystems, and strongly reactive to changes in the environment, yet the processes underlying this response remain unclear. Here we explore the role that community composition plays in shaping the bacterial metabolic response to resource gradients that occur along aquatic ecotones in a complex watershed in Quebec. Our results show that the response is mediated by complex shifts in community structure, and structural equation analysis confirmed two main pathways, one involving adjustments in the level of activity of existing phylotypes, and the other the replacement of the dominant phylotypes. These contrasting response pathways were not determined by the type or the intensity of the gradients involved, as we had hypothesized, but rather it would appear that some compositional configurations may be intrinsically more plastic than others. Our results suggest that community composition determines this overall level of community plasticity, but that composition itself may be driven by factors independent of the environmental gradients themselves, such that the response of bacterial communities to a given type of gradient may alternate between the adjustment and replacement pathways. We conclude that community composition influences the pathways of response in these bacterial communities, but not the metabolic outcome itself, which is driven by the environment, and which can be attained through multiple alternative configurations. PMID- 21980411 TI - Adaptation of organisms by resonance of RNA transcription with the cellular redox cycle. AB - Sequence variation in organisms differs across the genome and the majority of mutations are caused by oxidation, yet its origin is not fully understood. It has also been shown that the reduction-oxidation reaction cycle is the fundamental biochemical cycle that coordinates the timing of all biochemical processes in the cell, including energy production, DNA replication, and RNA transcription. We show that the temporal resonance of transcriptome biosynthesis with the oscillating binary state of the reduction-oxidation reaction cycle serves as a basis for non-random sequence variation at specific genome-wide coordinates that change faster than by accumulation of chance mutations. This work demonstrates evidence for a universal, persistent and iterative feedback mechanism between the environment and heredity, whereby acquired variation between cell divisions can outweigh inherited variation. PMID- 21980412 TI - AVPR1A variant associated with preschoolers' lower altruistic behavior. AB - The genetic origins of altruism, defined here as a costly act aimed to benefit non-kin individuals, have not been examined in young children. However, previous findings concerning adults pointed at the arginine vasopressin receptor 1A (AVPR1A) gene as a possible candidate. AVPR1A has been associated with a range of behaviors including aggressive, affiliative and altruistic phenotypes, and recently a specific allele (327 bp) of one of its promoter region polymorphisms (RS3) has been singled out in particular. We modeled altruistic behavior in preschoolers using a laboratory-based economic paradigm, a modified dictator game (DG), and tested for association between DG allocations and the RS3 "target allele." Using both population and family-based analyses we show a significant link between lower allocations and the RS3 "target allele," associating it, for the first time, with a lower proclivity toward altruistic behavior in children. This finding helps further the understanding of the intricate mechanisms underlying early altruistic behavior. PMID- 21980413 TI - Identifying Hendra virus diversity in pteropid bats. AB - Hendra virus (HeV) causes a zoonotic disease with high mortality that is transmitted to humans from bats of the genus Pteropus (flying foxes) via an intermediary equine host. Factors promoting spillover from bats to horses are uncertain at this time, but plausibly encompass host and/or agent and/or environmental factors. There is a lack of HeV sequence information derived from the natural bat host, as previously sequences have only been obtained from horses or humans following spillover events. In order to obtain an insight into possible variants of HeV circulating in flying foxes, collection of urine was undertaken in multiple flying fox roosts in Queensland, Australia. HeV was found to be geographically widespread in flying foxes with a number of HeV variants circulating at the one time at multiple locations, while at times the same variant was found circulating at disparate locations. Sequence diversity within variants allowed differentiation on the basis of nucleotide changes, and hypervariable regions in the genome were identified that could be used to differentiate circulating variants. Further, during the study, HeV was isolated from the urine of flying foxes on four occasions from three different locations. The data indicates that spillover events do not correlate with particular HeV isolates, suggesting that host and/or environmental factors are the primary determinants of bat-horse spillover. Thus future spillover events are likely to occur, and there is an on-going need for effective risk management strategies for both human and animal health. PMID- 21980414 TI - Meet me on the other side: trans-bilayer modulation of a model voltage-gated ion channel activity by membrane electrostatics asymmetry. AB - While it is accepted that biomembrane asymmetry is generated by proteins and phospholipids distribution, little is known about how electric changes manifested in a monolayer influence functional properties of proteins localized on the opposite leaflet. Herein we used single-molecule electrophysiology and investigated how asymmetric changes in the electrostatics of an artificial lipid membrane monolayer, generated oppositely from where alamethicin--a model voltage gated ion channel--was added, altered peptide activity. We found that phlorizin, a membrane dipole potential lowering amphiphile, augmented alamethicin activity and transport features, whereas the opposite occurred with RH-421, which enhances the monolayer dipole potential. Further, the monolayer surface potential was decreased via adsorption of sodium dodecyl sulfate, and demonstrated that vectorial modification of it also affected the alamethicin activity in a predictive manner. A new paradigm is suggested according to which asymmetric changes in the monolayer dipole and surface potential extend their effects spatially by altering the intramembrane potential, whose gradient is sensed by distantly located peptides. PMID- 21980415 TI - Identification of a conserved anti-apoptotic protein that modulates the mitochondrial apoptosis pathway. AB - Here we identified an evolutionarily highly conserved and ubiquitously expressed protein (C9orf82) that shows structural similarities to the death effector domain of apoptosis-related proteins. RNAi knockdown of C9orf82 induced apoptosis in A 549 and MCF7/casp3-10b lung and breast carcinoma cells, respectively, but not in cells lacking caspase-3, caspase-10 or both. Apoptosis was associated with activated caspases-3, -8, -9 and -10, and inactivation of caspases 10 or 3 was sufficient to block apoptosis in this pathway. Apoptosis upon knockdown of C9orf82 was associated with increased caspase-10 expression and activation, which was required for the generation of an 11 kDa tBid fragment and activation of Caspase-9. These data suggest that C9orf82 functions as an anti-apoptotic protein that modulates a caspase-10 dependent mitochondrial caspase-3/9 feedback amplification loop. We designate this ubiquitously expressed and evolutionarily conserved anti-apoptotic protein Conserved Anti-Apoptotic Protein (CAAP). We also demonstrated that treatment of MCF7/casp3-10b cells with staurosporine and etoposides induced apoptosis and knockdown of CAAP expression. This implies that the CAAP protein could be a target for chemotherapeutic agents. PMID- 21980416 TI - Characterization of an outbreak of hand, foot, and mouth disease in Nanchang, China in 2010. AB - Recent outbreaks of human enterovirus 71 (EV71) infection and EV71-associated hand, foot, and mouth disease (HFMD) in China have affected millions and potentially lead to life-threatening complications in newborns. Furthermore, these outbreaks represent a significant global public health issue in the world. Understanding the epidemiology of HFMD and EV71 infection and their transmission patterns in China is essential for controlling outbreaks. However, no studies on the outbreaks of HFMD and EV71 infection in China during 2010 have been reported. In this report, we carried out an epidemiological analysis to study an outbreak of HFMD and EV71 infection in 2010 in the city of Nanchang in the Jiangxi province of People's Republic of China. From April 7 to May 11, 2010, a total of 109 HFMD cases were reported, and in this report the HFMD cases were studied by both epidemiological and laboratory analyses. The epidemiological study indicates that children aged younger than 8 years old represented more than 90% of the reported cases, with the age group of 1-3 years containing the highest number of cases. Laboratory studies detected a high prevalence of EV71 amongst the cases in our study, suggesting EV71 as a common enterovirus found in HFMD cases in Nanchang. Phylogenetic analysis of the sequence of the VP1 region of four EV71 isolates indicated that the Nanchang strains belong to the C4 subgenotype commonly found in China during outbreaks in 2008 but contain distinct variations from these strains. Our study for the first time characterizes the epidemiology of HFMD and EV71 infection in China in 2010 and furthermore, provides the first direct evidence of the genotype of EV71 circulating in Nanchang, China. Our study should facilitate the development of public health measures for the control and prevention of HFMD and EV71 infection in at-risk individuals in China. PMID- 21980417 TI - The orphan gene ybjN conveys pleiotropic effects on multicellular behavior and survival of Escherichia coli. AB - YbjN, encoding an enterobacteria-specific protein, is a multicopy suppressor of temperature sensitivity in the ts9 mutant strain of Escherichia coli. In this study, we further explored the role(s) of ybjN. First, we demonstrated that the ybjN transcript was about 10-fold lower in the ts9 strain compared to that of E. coli strain BW25113 (BW). Introduction of multiple copies of ybjN in the ts9 strain resulted in over-expression of ybjN by about 10-fold as compared to that of BW. These results suggested that temperature sensitivity of the ts9 mutant of E. coli may be related to expression levels of ybjN. Characterization of E. coli ybjN mutant revealed that ybjN mutation resulted in pleiotropic phenotypes, including increased motility, fimbriation (auto-aggregation), exopolysaccharide production, and biofilm formation. In contrast, over-expression of ybjN (in terms of multiple copies) resulted in reduced motility, fimbriation, exopolysaccharide production, biofilm formation and acid resistance. In addition, our results indicate that a ybjN-homolog gene from Erwinia amylovora, a plant enterobacterial pathogen, is functionally conserved with that of E. coli, suggesting similar evolution of the YbjN family proteins in enterobacteria. A microarray study revealed that the expression level of ybjN was inversely correlated with the expression of flagellar, fimbrial and acid resistance genes. Over-expression of ybjN significantly down-regulated genes involved in citric acid cycle, glycolysis, the glyoxylate shunt, oxidative phosphorylation, amino acid and nucleotide metabolism. Furthermore, over-expression of ybjN up-regulated toxin antitoxin modules, the SOS response pathway, cold shock and starvation induced transporter genes. Collectively, these results suggest that YbjN may play important roles in regulating bacterial multicellular behavior, metabolism, and survival under stress conditions in E. coli. These results also suggest that ybjN over-expression-related temperature rescue of the ts9 mutant may be due to down regulation of metabolic activity and activation of stress response genes in the ts9 mutant. PMID- 21980418 TI - Classification and analysis of regulatory pathways using graph property, biochemical and physicochemical property, and functional property. AB - Given a regulatory pathway system consisting of a set of proteins, can we predict which pathway class it belongs to? Such a problem is closely related to the biological function of the pathway in cells and hence is quite fundamental and essential in systems biology and proteomics. This is also an extremely difficult and challenging problem due to its complexity. To address this problem, a novel approach was developed that can be used to predict query pathways among the following six functional categories: (i) "Metabolism", (ii) "Genetic Information Processing", (iii) "Environmental Information Processing", (iv) "Cellular Processes", (v) "Organismal Systems", and (vi) "Human Diseases". The prediction method was established trough the following procedures: (i) according to the general form of pseudo amino acid composition (PseAAC), each of the pathways concerned is formulated as a 5570-D (dimensional) vector; (ii) each of components in the 5570-D vector was derived by a series of feature extractions from the pathway system according to its graphic property, biochemical and physicochemical property, as well as functional property; (iii) the minimum redundancy maximum relevance (mRMR) method was adopted to operate the prediction. A cross-validation by the jackknife test on a benchmark dataset consisting of 146 regulatory pathways indicated that an overall success rate of 78.8% was achieved by our method in identifying query pathways among the above six classes, indicating the outcome is quite promising and encouraging. To the best of our knowledge, the current study represents the first effort in attempting to identity the type of a pathway system or its biological function. It is anticipated that our report may stimulate a series of follow-up investigations in this new and challenging area. PMID- 21980419 TI - Human biodistribution and dosimetry of 11C-CUMI-101, an agonist radioligand for serotonin-1a receptors in brain. AB - As a reported agonist, 11C-CUMI-101 is believed to selectively bind the G-protein coupled state of the serotonin-1A (5-HT(1A)) receptor, thereby providing a measure of the active subset of all 5-HT(1A) receptors in brain. Although 11C CUMI-101 has been successfully used to quantify 5-HT(1A) receptors in human and monkey brain, its radiation exposure has not previously been reported. The purpose of this study was to calculate the radiation exposure to organs of the body based on serial whole-body imaging with positron emission tomography (PET) in human subjects. METHODS: Nine healthy volunteers were injected with 428+/-84 MBq (mean +/- SD) (11)C-CUMI-101 and then imaged with a PET-only device for two hours from head to mid-thigh. Eleven source organs (brain, heart, liver, pancreas, stomach, spleen, lungs, kidneys, lumbar spine L1-5, thyroid, and urinary bladder) were identified on whole body images and used to calculate radiation doses using the software program OLINDA/EXM 1.1. To confirm that we had correctly identified the pancreas, a tenth subject was imaged on a PET/CT device. RESULTS: Brain had high uptake (~11% of injected activity (IA)) at 10 min. Although liver had the highest uptake (~35% IA at 120 min), excretion of this activity was not visible in gall bladder or intestine during the scanning session. Organs which received the highest doses (microSv/MBq) were pancreas (32.0), liver (18.4), and spleen (14.5). The effective dose of 11C-CUMI-101 was 5.3+/-0.5 microSv/MBq. CONCLUSION: The peak brain uptake (~11% IA) of 11C-CUMI 101 is the highest among more than twenty 11C-labeled ligands reported in the literature and provides good counting statistics from relatively low injected activities. Similar to that of other 11C-labeled ligands for brain imaging, the effective dose of 11C-CUMI-101 is 5.3+/-0.5 microSv/MBq, a value that can now be used to estimate the radiation risks in future research studies. PMID- 21980420 TI - A type 2C protein phosphatase FgPtc3 is involved in cell wall integrity, lipid metabolism, and virulence in Fusarium graminearum. AB - Type 2C protein phosphatases (PP2Cs) play important roles in regulating many biological processes in eukaryotes. Currently, little is known about functions of PP2Cs in filamentous fungi. The causal agent of wheat head blight, Fusarium graminearum, contains seven putative PP2C genes, FgPTC1, -3, -5, -5R, -6, -7 and 7R. In order to investigate roles of these PP2Cs, we constructed deletion mutants for all seven PP2C genes in this study. The FgPTC3 deletion mutant (DeltaFgPtc3 8) exhibited reduced aerial hyphae formation and deoxynivalenol (DON) production, but increased production of conidia. The mutant showed increased resistance to osmotic stress and cell wall-damaging agents on potato dextrose agar plates. Pathogencity assays showed that DeltaFgPtc3-8 is unable to infect flowering wheat head. All of the defects were restored when DeltaFgPtc3-8 was complemented with the wild-type FgPTC3 gene. Additionally, the FgPTC3 partially rescued growth defect of a yeast PTC1 deletion mutant under various stress conditions. Ultrastructural and histochemical analyses showed that conidia of DeltaFgPtc3-8 contained an unusually high number of large lipid droplets. Furthermore, the mutant accumulated a higher basal level of glycerol than the wild-type progenitor. Quantitative real-time PCR assays showed that basal expression of FgOS2, FgSLT2 and FgMKK1 in the mutant was significantly higher than that in the wild-type strain. Serial analysis of gene expression in DeltaFgPtc3-8 revealed that FgPTC3 is associated with various metabolic pathways. In contrast to the FgPTC3 mutant, the deletion mutants of FgPTC1, FgPTC5, FgPTC5R, FgPTC6, FgPTC7 or FgPTC7R did not show aberrant phenotypic features when grown on PDA medium or inoculated on wheat head. These results indicate FgPtc3 is the key PP2C that plays a critical role in a variety of cellular and biological functions, including cell wall integrity, lipid and secondary metabolisms, and virulence in F. graminearum. PMID- 21980421 TI - Determinants of nucleotide-binding selectivity of malic enzyme. AB - Malic enzymes have high cofactor selectivity. An isoform-specific distribution of residues 314, 346, 347 and 362 implies that they may play key roles in determining the cofactor specificity. Currently, Glu314, Ser346, Lys347 and Lys362 in human c-NADP-ME were changed to the corresponding residues of human m NAD(P)-ME (Glu, Lys, Tyr and Gln, respectively) or Ascaris suum m-NAD-ME (Ala, Ile, Asp and His, respectively). Kinetic data demonstrated that the S346K/K347Y/K362Q c-NADP-ME was transformed into a debilitated NAD+-utilizing enzyme, as shown by a severe decrease in catalytic efficiency using NADP+ as the cofactor without a significant increase in catalysis using NAD+ as the cofactor. However, the S346K/K347Y/K362H enzyme displayed an enhanced value for k(cat,NAD), suggesting that His at residue 362 may be more beneficial than Gln for NAD+ binding. Furthermore, the S346I/K347D/K362H mutant had a very large K(m,NADP) value compared to other mutants, suggesting that this mutant exclusively utilizes NAD+ as its cofactor. Since the S346K/K347Y/K362Q, S346K/K347Y/K362H and S346I/K347D/K362H c-NADP-ME mutants did not show significant reductions in their K(m,NAD) values, the E314A mutation was then introduced into these triple mutants. Comparison of the kinetic parameters of each triple-quadruple mutant pair (for example, S346K/K347Y/K362Q versus E314A/S346K/K347Y/K362Q) revealed that all of the K(m) values for NAD+ and NADP(+) of the quadruple mutants were significantly decreased, while either k(cat,NAD) or k(cat,NADP) was substantially increased. By adding the E314A mutation to these triple mutant enzymes, the E314A/S346K/K347Y/K362Q, E314A/S346K/K347Y/K362H and E314A/S346I/K347D/K362H c NADP-ME variants are no longer debilitated but become mainly NAD+-utilizing enzymes by a considerable increase in catalysis using NAD+ as the cofactor. These results suggest that abolishing the repulsive effect of Glu314 in these quadruple mutants increases the binding affinity of NAD+. Here, we demonstrate that a series of E314A-containing c-NADP-ME quadruple mutants have been changed to NAD+ utilizing enzymes by abrogating NADP+ binding and increasing NAD+ binding. PMID- 21980422 TI - Identification of Trypanosoma brucei RMI1/BLAP75 homologue and its roles in antigenic variation. AB - At any time, each cell of the protozoan parasite Trypanosoma brucei expresses a single species of its major antigenic protein, the variant surface glycoprotein (VSG), from a repertoire of >2,000 VSG genes and pseudogenes. The potential to express different VSGs by transcription and recombination allows the parasite to escape the antibody-mediated host immune response, a mechanism known as antigenic variation. The active VSG is transcribed from a sub-telomeric polycistronic unit called the expression site (ES), whose promoter is 40-60 kb upstream of the VSG. While the mechanisms that initiate recombination remain unclear, the resolution phase of these reactions results in the recombinational replacement of the expressed VSG with a donor from one of three distinct chromosomal locations; sub telomeric loci on the 11 essential chromosomes, on minichromosomes, or at telomere-distal loci. Depending on the type of recombinational replacement (single or double crossover, duplicative gene conversion, etc), several DNA repair pathways have been thought to play a role. Here we show that VSG recombination relies on at least two distinct DNA-repair pathways, one of which requires RMI1-TOPO3alpha to suppress recombination and one that is dependent on RAD51 and RMI1. These genetic interactions suggest that both RAD51-dependent and RAD51-independent recombination pathways operate in antigenic switching and that trypanosomes differentially utilize recombination factors for VSG switching, depending on currently unknown parameters within the ES. PMID- 21980423 TI - Predictors of death among patients who completed tuberculosis treatment: a population-based cohort study. AB - BACKGROUND: Mortality among patients who complete tuberculosis (TB) treatment is still high among vulnerable populations. The objective of the study was to identify the probability of death and its predictive factors in a cohort of successfully treated TB patients. METHODS: A population-based retrospective longitudinal study was performed in Barcelona, Spain. All patients who successfully completed TB treatment with culture-confirmation and available drug susceptibility testing between 1995-1997 were retrospectively followed-up until December 31, 2005 by the Barcelona TB Control Program. Socio-demographic, clinical, microbiological and treatment variables were examined. Mortality, TB Program and AIDS registries were reviewed. Kaplan-Meier and a Cox regression methods with time-dependent covariates were used for the survival analysis, calculating the hazard ratio (HR) with 95% confidence intervals (CI). RESULTS: Among the 762 included patients, the median age was 36 years, 520 (68.2%) were male, 178 (23.4%) HIV-infected, and 208 (27.3%) were alcohol abusers. Of the 134 (17.6%) injecting drug users (IDU), 123 (91.8%) were HIV-infected. A total of 30 (3.9%) recurrences and 173 deaths (22.7%) occurred (mortality rate: 3.4/100 person-years of follow-up). The predictors of death were: age between 41-60 years old (HR: 3.5; CI:2.1-5.7), age greater than 60 years (HR: 14.6; CI:8.9-24), alcohol abuse (HR: 1.7; CI:1.2-2.4) and HIV-infected IDU (HR: 7.9; CI:4.7-13.3). CONCLUSIONS: The mortality rate among TB patients who completed treatment is associated with vulnerable populations such as the elderly, alcohol abusers, and HIV-infected IDU. We therefore need to fight against poverty, and promote and develop interventions and social policies directed towards these populations to improve their survival. PMID- 21980424 TI - Obesity risk gene TMEM18 encodes a sequence-specific DNA-binding protein. AB - Transmembrane protein 18 (TMEM18) has previously been connected to cell migration and obesity. However, the molecular function of the protein has not yet been described. Here we show that TMEM18 localises to the nuclear membrane and binds to DNA in a sequence-specific manner. The protein binds DNA with its positively charged C-terminus that contains also a nuclear localisation signal. Increase in the amount of TMEM18 in cells suppresses expression from a reporter vector with the TMEM18 target sequence. TMEM18 is a small protein of 140 residues and is predicted to be mostly alpha-helical with three transmembrane parts. As a consequence the DNA binding by TMEM18 would bring the chromatin very near to nuclear membrane. We speculate that this closed perinuclear localisation of TMEM18-bound DNA might repress transcription from it. PMID- 21980425 TI - Dysregulation of gene expression in the artificial human trisomy cells of chromosome 8 associated with transformed cell phenotypes. AB - A change in chromosome number, known as aneuploidy, is a common characteristic of cancer. Aneuploidy disrupts gene expression in human cancer cells and immortalized human epithelial cells, but not in normal human cells. However, the relationship between aneuploidy and cancer remains unclear. To study the effects of aneuploidy in normal human cells, we generated artificial cells of human primary fibroblast having three chromosome 8 (trisomy 8 cells) by using microcell mediated chromosome transfer technique. In addition to decreased proliferation, the trisomy 8 cells lost contact inhibition and reproliferated after exhibiting senescence-like characteristics that are typical of transformed cells. Furthermore, the trisomy 8 cells exhibited chromosome instability, and the overall gene expression profile based on microarray analyses was significantly different from that of diploid human primary fibroblasts. Our data suggest that aneuploidy, even a single chromosome gain, can be introduced into normal human cells and causes, in some cases, a partial cancer phenotype due to a disruption in overall gene expression. PMID- 21980426 TI - Atorvastatin therapy during the peri-infarct period attenuates left ventricular dysfunction and remodeling after myocardial infarction. AB - Although statins impart a number of cardiovascular benefits, whether statin therapy during the peri-infarct period improves subsequent myocardial structure and function remains unclear. Thus, we evaluated the effects of atorvastatin on cardiac function, remodeling, fibrosis, and apoptosis after myocardial infarction (MI). Two groups of rats were subjected to permanent coronary occlusion. Group II (n = 14) received oral atorvastatin (10 mg/kg/d) daily for 3 wk before and 4 wk after MI, while group I (n = 12) received equivalent doses of vehicle. Infarct size (Masson's trichrome-stained sections) was similar in both groups. Compared with group I, echocardiographic left ventricular ejection fraction (LVEF) and fractional area change (FAC) were higher while LV end-diastolic volume (LVEDV) and LV end-systolic and end-diastolic diameters (LVESD and LVEDD) were lower in treated rats. Hemodynamically, atorvastatin-treated rats exhibited significantly higher dP/dt(max), end-systolic elastance (Ees), and preload recruitable stroke work (PRSW) and lower LV end-diastolic pressure (LVEDP). Morphometrically, infarct wall thickness was greater in treated rats. The improvement of LV function by atorvastatin was associated with a decrease in hydroxyproline content and in the number of apoptotic cardiomyocyte nuclei. We conclude that atorvastatin therapy during the peri-infarct period significantly improves LV function and limits adverse LV remodeling following MI independent of a reduction in infarct size. These salubrious effects may be due in part to a decrease in myocardial fibrosis and apoptosis. PMID- 21980427 TI - Transketolase-like 1 expression is modulated during colorectal cancer progression and metastasis formation. AB - BACKGROUND: Transketolase-like 1 (TKTL1) induces glucose degradation through anaerobic pathways, even in presence of oxygen, favoring the malignant aerobic glycolytic phenotype characteristic of tumor cells. As TKTL1 appears to be a valid biomarker for cancer prognosis, the aim of the current study was to correlate its expression with tumor stage, probability of tumor recurrence and survival, in a series of colorectal cancer patients. METHODOLODY/PRINCIPAL FINDINGS: Tumor tissues from 63 patients diagnosed with colorectal cancer at different stages of progression were analyzed for TKTL1 by immunohistochemistry. Staining was quantified by computational image analysis, and correlations between enzyme expression, local growth, lymph-node involvement and metastasis were assessed. The highest values for TKTL1 expression were detected in the group of stage III tumors, which showed significant differences from the other groups (Kruskal-Wallis test, P = 0.000008). Deeper analyses of T, N and M classifications revealed a weak correlation between local tumor growth and enzyme expression (Mann-Whitney test, P = 0.029), a significant association of the enzyme expression with lymph-node involvement (Mann-Whitney test, P = 0.0014) and a significant decrease in TKTL1 expression associated with metastasis (Mann Whitney test, P = 0.0004). CONCLUSIONS/SIGNIFICANCE: To our knowledge, few studies have explored the association between variations in TKTL1 expression in the primary tumor and metastasis formation. Here we report downregulation of enzyme expression when metastasis appears, and a correlation between enzyme expression and regional lymph-node involvement in colon cancer. This finding may improve our understanding of metastasis and lead to new and more efficient therapies against cancer. PMID- 21980428 TI - Genetic susceptibility to acute rheumatic fever: a systematic review and meta analysis of twin studies. AB - BACKGROUND: Acute rheumatic fever is considered to be a heritable condition, but the magnitude of the genetic effect is unknown. The objective of this study was to conduct a systematic review and meta-analysis of twin studies of concordance of acute rheumatic fever in order to derive quantitative estimates of the size of the genetic effect. METHODS: We searched PubMed/MEDLINE, ISI Web of Science, EMBASE, and Google Scholar from their inception to 31 January 2011, and bibliographies of retrieved articles, for twin studies of the concordance for acute rheumatic fever or rheumatic heart disease in monozygotic versus dizygotic twins that used accepted diagnostic criteria for acute rheumatic fever and zygosity without age, gender or language restrictions. Twin similarity was measured by probandwise concordance rate and odds ratio (OR), and aggregate probandwise concordance risk was calculated by combining raw data from each study. ORs from separate studies were combined by random-effects meta-analysis to evaluate association between zygosity status and concordance. Heritability was estimated by fitting a variance components model to the data. RESULTS: 435 twin pairs from six independent studies met the inclusion criteria. The pooled probandwise concordance risk for acute rheumatic fever was 44% in monozygotic twins and 12% in dizygotic twins, and the association between zygosity and concordance was strong (OR 6.39; 95% confidence interval, 3.39 to 12.06; P<0.001), with no significant study heterogeneity (P = 0.768). The estimated heritability across all the studies was 60%. CONCLUSIONS: Acute rheumatic fever is an autoimmune disorder with a high heritability. The discovery of all genetic susceptibility loci through whole genome scanning may provide a clinically useful genetic risk prediction tool for acute rheumatic fever and its sequel, rheumatic heart disease. PMID- 21980429 TI - Inhibition of glycogen synthase kinase-3beta counteracts ligand-independent activity of the androgen receptor in castration resistant prostate cancer. AB - In order to generate genomic signals, the androgen receptor (AR) has to be transported into the nucleus upon androgenic stimuli. However, there is evidence from in vitro experiments that in castration-resistant prostate cancer (CRPC) cells the AR is able to translocate into the nucleus in a ligand-independent manner. The recent finding that inhibition of the glycogen-synthase-kinase 3beta (GSK-3beta) induces a rapid nuclear export of the AR in androgen-stimulated prostate cancer cells prompted us to analyze the effects of a GSK-3beta inhibition in the castration-resistant LNCaP sublines C4-2 and LNCaP-SSR. Both cell lines exhibit high levels of nuclear AR in the absence of androgenic stimuli. Exposure of these cells to the maleimide SB216763, a potent GSK-3beta inhibitor, resulted in a rapid nuclear export of the AR even under androgen deprived conditions. Moreover, the ability of C4-2 and LNCaP-SSR cells to grow in the absence of androgens was diminished after pharmacological inhibition of GSK 3beta in vitro. The ability of SB216763 to modulate AR signalling and function in CRPC in vivo was additionally demonstrated in a modified chick chorioallantoic membrane xenograft assay after systemic delivery of SB216763. Our data suggest that inhibition of GSK-3beta helps target the AR for export from the nucleus thereby diminishing the effects of mislocated AR in CRPC cells. Therefore, inhibition of GSK-3beta could be an interesting new strategy for the treatment of CRPC. PMID- 21980430 TI - Up-regulation of kin17 is essential for proliferation of breast cancer. AB - BACKGROUND: Kin17 is ubiquitously expressed at low levels in human tissue and participates in DNA replication, DNA repair and cell cycle control. Breast cancer cells are characterized by enabling replicative immortality and accumulated DNA damage. However, whether kin17 contributes to breast carcinogenesis remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we show for the first time that kin17 is an important molecule related to breast cancer. Our results show that kin17 expression was markedly increased in clinical breast tumors and was associated with tumor grade, Ki-67 expression, p53 mutation status and progesterone receptor expression, which were assessed in a clinicopathologic characteristics review. Knockdown of kin17 inhibited DNA replication and repair, blocked cell cycle progression and inhibited anchorage-independent growth, while increasing sensitivity to chemotherapy in breast cancer cells. Moreover, kin17 silencing decreased EGF-stimulated cell growth. Furthermore, overexpression of kin17 promoted DNA replication and cell proliferation in MCF-10A. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that up-regulation of kin17 is strongly associated with cellular proliferation, DNA replication, DNA damage response and breast cancer development. The increased level of kin17 was not only a consequence of immortalization but also associated with tumorigenesis. Therefore, kin17 could be a novel therapeutic target for inhibiting cell growth in breast cancer. PMID- 21980431 TI - Reversible resistance induced by FLT3 inhibition: a novel resistance mechanism in mutant FLT3-expressing cells. AB - OBJECTIVES: Clinical responses achieved with FLT3 kinase inhibitors in acute myeloid leukemia (AML) are typically transient and partial. Thus, there is a need for identification of molecular mechanisms of clinical resistance to these drugs. In response, we characterized MOLM13 AML cell lines made resistant to two structurally-independent FLT3 inhibitors. METHODS: MOLM13 cells were made drug resistant via prolonged exposure to midostaurin and HG-7-85-01, respectively. Cell proliferation was determined by Trypan blue exclusion. Protein expression was assessed by immunoblotting, immunoprecipitation, and flow cytometry. Cycloheximide was used to determine protein half-life. RT-PCR was performed to determine FLT3 mRNA levels, and FISH analysis was performed to determine FLT3 gene expression. RESULTS AND CONCLUSIONS: We found that MOLM13 cells readily developed cross-resistance when exposed to either midostaurin or HG-7-85-01. Resistance in both lines was associated with dramatically elevated levels of cell surface FLT3 and elevated levels of phosphor-MAPK, but not phospho-STAT5. The increase in FLT3-ITD expression was at least in part due to reduced turnover of the receptor, with prolonged half-life. Importantly, the drug-resistant phenotype could be rapidly reversed upon withdrawal of either inhibitor. Consistent with this phenotype, no significant evidence of FLT3 gene amplification, kinase domain mutations, or elevated levels of mRNA was observed, suggesting that protein turnover may be part of an auto-regulatory pathway initiated by FLT3 kinase activity. Interestingly, FLT3 inhibitor resistance also correlated with resistance to cytosine arabinoside. Over-expression of FLT3 protein in response to kinase inhibitors may be part of a novel mechanism that could contribute to clinical resistance. PMID- 21980432 TI - Transcriptional networks in epithelial-mesenchymal transition. AB - BACKGROUND: Epithelial-mesenchymal transition (EMT) changes polarized epithelial cells into migratory phenotypes associated with loss of cell-cell adhesion molecules and cytoskeletal rearrangements. This form of plasticity is seen in mesodermal development, fibroblast formation, and cancer metastasis. METHODS AND FINDINGS: Here we identify prominent transcriptional networks active during three time points of this transitional process, as epithelial cells become fibroblasts. DNA microarray in cultured epithelia undergoing EMT, validated in vivo, were used to detect various patterns of gene expression. In particular, the promoter sequences of differentially expressed genes and their transcription factors were analyzed to identify potential binding sites and partners. The four most frequent cis-regulatory elements (CREs) in up-regulated genes were SRY, FTS-1, Evi-1, and GC-Box, and RNA inhibition of the four transcription factors, Atf2, Klf10, Sox11, and SP1, most frequently binding these CREs, establish their importance in the initiation and propagation of EMT. Oligonucleotides that block the most frequent CREs restrain EMT at early and intermediate stages through apoptosis of the cells. CONCLUSIONS: Our results identify new transcriptional interactions with high frequency CREs that modulate the stability of cellular plasticity, and may serve as targets for modulating these transitional states in fibroblasts. PMID- 21980433 TI - The SOCS2 ubiquitin ligase complex regulates growth hormone receptor levels. AB - Growth Hormone is essential for the regulation of growth and the homeostatic control of intermediary metabolism. GH actions are mediated by the Growth Hormone Receptor; a member of the cytokine receptor super family that signals chiefly through the JAK2/STAT5 pathway. Target tissue responsiveness to GH is under regulatory control to avoid excessive and off-target effects upon GHR activation. The suppressor of cytokine signalling 2 (SOCS) is a key regulator of GHR sensitivity. This is clearly shown in mice where the SOCS2 gene has been inactivated, which show 30-40% increase in body length, a phenotype that is dependent on endogenous GH secretion. SOCS2 is a GH-stimulated, STAT5b-regulated gene that acts in a negative feedback loop to downregulate GHR signalling. Since the biochemical basis for these actions is poorly understood, we studied the molecular function of SOCS2. We demonstrated that SOCS2 is part of a multimeric complex with intrinsic ubiquitin ligase activity. Mutational analysis shows that the interaction with Elongin B/C controls SOCS2 protein turnover and affects its molecular activity. Increased GHR levels were observed in livers from SOCS2-/- mice and in the absence of SOCS2 in in vitro experiments. We showed that SOCS2 regulates cellular GHR levels through direct ubiquitination and in a proteasomally dependent manner. We also confirmed the importance of the SOCS-box for the proper function of SOCS2. Finally, we identified two phosphotyrosine residues in the GHR to be responsible for the interaction with SOCS2, but only Y487 to account for the effects of SOCS2. The demonstration that SOCS2 is an ubiquitin ligase for the GHR unveils the molecular basis for its physiological actions. PMID- 21980434 TI - Acetylation of the proto-oncogene EVI1 abrogates Bcl-xL promoter binding and induces apoptosis. AB - EVI1 (Ecotropic Viral Integration site I), which was originally identified as a myeloid transforming gene by means of retroviral insertional mutagenesis in mouse leukemia, encodes a nuclear DNA binding zinc finger protein. The presence of zinc fingers that are able to bind to specific sequences of DNA suggests that EVI1 is a transcriptional regulator; however, except a few, target genes of EVI1 are poorly functionally identified thus far. In this study we provide evidence that EVI1 directly induces the expression of Bcl-xL through the first set of zinc finger and thereby inhibits apoptosis. ChIP analysis showed that EVI1 binds to the Bcl-xL promoter in HT-29 cells, a colon carcinoma cell line, which expresses EVI1. The observation is also supported by the fact that EVI1 siRNA treated HT-29 cells, shows a down regulation of Bcl-xL expression and that over expression of EVI1 results in the induction of the Bcl-xL reporter construct. A set of EVI1 positive chronic myeloid leukemia (CML) samples also showed higher Bcl-xL expression with respect to EVI1 negative samples. Interestingly, co-expression of EVI1 with wild type, but not with dominant-negative form of PCAF, abolishes the effect of EVI1 on Bcl-xL, indicating that acetylation of EVI1 abrogates its ability not only to bind Bcl-xL promoter but also alleviate Bcl-xL activity. Finally we have shown that EVI1 expression regulates apoptosis in HT-29 cells, which is abrogated when HT-29 cells are transfected with EVI1 siRNA or PCAF. The result for the first time shows a direct pathway by which EVI1 can protect cells from apoptosis and also demonstrates that the pathway can be reversed when EVI1 is acetylated. PMID- 21980435 TI - Dopamine and octopamine influence avoidance learning of honey bees in a place preference assay. AB - Biogenic amines are widely characterized in pathways evaluating reward and punishment, resulting in appropriate aversive or appetitive responses of vertebrates and invertebrates. We utilized the honey bee model and a newly developed spatial avoidance conditioning assay to probe effects of biogenic amines octopamine (OA) and dopamine (DA) on avoidance learning. In this new protocol non-harnessed bees associate a spatial color cue with mild electric shock punishment. After a number of experiences with color and shock the bees no longer enter the compartment associated with punishment. Intrinsic aspects of avoidance conditioning are associated with natural behavior of bees such as punishment (lack of food, explosive pollination mechanisms, danger of predation, heat, etc.) and their association to floral traits or other spatial cues during foraging. The results show that DA reduces the punishment received whereas octopamine OA increases the punishment received. These effects are dose-dependent and specific to the acquisition phase of training. The effects during acquisition are specific as shown in experiments using the antagonists Pimozide and Mianserin for DA and OA receptors, respectively. This study demonstrates the integrative role of biogenic amines in aversive learning in the honey bee as modeled in a novel non-appetitive avoidance learning assay. PMID- 21980436 TI - Changes in parasitoid communities over time and space: a historical case study of the maize pest Ostrinia nubilalis. AB - Understanding the ways in which human environmental modifications affect biodiversity is a key challenge in conservation planning, pest control and evolutionary ecology. Parasitoid communities, particularly those associated with agricultural pests, may be susceptible to such modifications. We document here changes in the larval parasitoid communities of Ostrinia nubilalis--the main pest of maize--and its sibling species O. scapulalis, based on two historical datasets, one collected from 1921-1928 and the other from 2001-2005. Each of these datasets encompasses several years and large geographical areas and was based on several thousands/millions of host larvae. The 80-year interval between the two datasets was marked by a decrease in O. nubilalis parasitism to about two thirds its initial level, mostly due to a decrease in the rate of parasitism by hymenopterans. However, a well balanced loss and gain of species ensured that species richness remained stable. Conversely, O. scapulalis displayed stable rates of parasitism over this period, with a decline in the species richness of its parasitoid community. Rates of parasitism and species richness in regions colonized by O. nubilalis during the 1950s were one half to one third those in regions displaying long-term colonisation by this pest. During the recent human activity-driven expansion of its range, O. nubilalis has neither captured native parasitoids nor triggered parasite spill back or spill over. PMID- 21980437 TI - How long do the dead survive on the road? Carcass persistence probability and implications for road-kill monitoring surveys. AB - BACKGROUND: Road mortality is probably the best-known and visible impact of roads upon wildlife. Although several factors influence road-kill counts, carcass persistence time is considered the most important determinant underlying underestimates of road mortality. The present study aims to describe and model carcass persistence variability on the road for different taxonomic groups under different environmental conditions throughout the year; and also to assess the effect of sampling frequency on the relative variation in road-kill estimates registered within a survey. METHODOLOGY/PRINCIPAL FINDINGS: Daily surveys of road killed vertebrates were conducted over one year along four road sections with different traffic volumes. Survival analysis was then used to i) describe carcass persistence timings for overall and for specific animal groups; ii) assess optimal sampling designs according to research objectives; and iii) model the influence of road, animal and weather factors on carcass persistence probabilities. Most animal carcasses persisted on the road for the first day only, with some groups disappearing at very high rates. The advisable periodicity of road monitoring that minimizes bias in road mortality estimates is daily monitoring for bats (in the morning) and lizards (in the afternoon), daily monitoring for toads, small birds, small mammals, snakes, salamanders, and lagomorphs; 1 day-interval (alternate days) for large birds, birds of prey, hedgehogs, and freshwater turtles; and 2 day-interval for carnivores. Multiple factors influenced the persistence probabilities of vertebrate carcasses on the road. Overall, the persistence was much lower for small animals, on roads with lower traffic volumes, for carcasses located on road lanes, and during humid conditions and high temperatures during the wet season and dry seasons, respectively. CONCLUSION/SIGNIFICANCE: The guidance given here on monitoring frequencies is particularly relevant to provide conservation and transportation agencies with accurate numbers of road-kills, realistic mitigation measures, and detailed designs for road monitoring programs. PMID- 21980438 TI - Type III IFN receptor expression and functional characterisation in the pteropid bat, Pteropus alecto. AB - Bats are rich reservoir hosts for a variety of viruses, many of which are capable of spillover to other susceptible mammals with lethal consequences. The ability of bats to remain asymptomatic to viral infection may be due to the rapid control of viral replication very early in the immune response through innate antiviral mechanisms. Type I and III interferons (IFNs) represent the first line of defence against viral infection in mammals, with both families of IFNs present in pteropid bats. To obtain further insight into the type III IFN system in bats, we describe the characterization of the type III IFN receptor (IFNlambdaR) in the black flying fox, P. alecto with the characterization of IFNlambdaR1 and IL10R2 genes that make up the type III IFN receptor complex. The bat IFNlambdaR complex has a wide tissue distribution and at the cellular level, both epithelial and immune cells are responsive to IFN-lambda treatment. Furthermore, we demonstrate that the bat IFNlambdaR1 chain acts as a functional receptor. To our knowledge, this report represents the first description of an IFN receptor in any species of bat. The responsiveness of bat cells to IFN-lambda support a role for the type III IFN system by epithelial and immune cells in bats. PMID- 21980440 TI - Multi-modal courtship in the peacock spider, Maratus volans (O.P.-Cambridge, 1874). AB - The peacock spider, Maratus volans, has one of the most elaborate courtship displays in arthropods. Using regular and high-speed video segments captured in the lab, we provide detailed descriptions of complete male courtship dances. As research on jumping spiders has demonstrated that males of some species produce vibrations concurrently with visual displays, we also used laser vibrometry to uncover such elements for this species. Our recordings reveal and describe for the first time, that M. volans males use vibratory signals in addition to complex body ornaments and motion displays. The peacock spider and other closely related species are outstanding study organisms for testing hypotheses about the evolution and functional significance of complex displays, thus, this descriptive study establishes a new model system for behavioral ecology, one that certainly stands to make important contributions to the field. PMID- 21980439 TI - A systems genetics approach provides a bridge from discovered genetic variants to biological pathways in rheumatoid arthritis. AB - Genome-wide association studies (GWAS) have yielded novel genetic loci underlying common diseases. We propose a systems genetics approach to utilize these discoveries for better understanding of the genetic architecture of rheumatoid arthritis (RA). Current evidence of genetic associations with RA was sought through PubMed and the NHGRI GWAS catalog. The associations of 15 single nucleotide polymorphisms and HLA-DRB1 alleles were confirmed in 1,287 cases and 1,500 controls of Japanese subjects. Among these, HLA-DRB1 alleles and eight SNPs showed significant associations and all but one of the variants had the same direction of effect as identified in the previous studies, indicating that the genetic risk factors underlying RA are shared across populations. By receiver operating characteristic curve analysis, the area under the curve (AUC) for the genetic risk score based on the selected variants was 68.4%. For seropositive RA patients only, the AUC improved to 70.9%, indicating good but suboptimal predictive ability. A simulation study shows that more than 200 additional loci with similar effect size as recent GWAS findings or 20 rare variants with intermediate effects are needed to achieve AUC = 80.0%. We performed the random walk with restart (RWR) algorithm to prioritize genes for future mapping studies. The performance of the algorithm was confirmed by leave-one-out cross-validation. The RWR algorithm pointed to ZAP70 in the first rank, in which mutation causes RA like autoimmune arthritis in mice. By applying the hierarchical clustering method to a subnetwork comprising RA-associated genes and top-ranked genes by the RWR, we found three functional modules relevant to RA etiology: "leukocyte activation and differentiation", "pattern-recognition receptor signaling pathway", and "chemokines and their receptors".These results suggest that the systems genetics approach is useful to find directions of future mapping strategies to illuminate biological pathways. PMID- 21980441 TI - Immunoglobulin free light chains are increased in hypersensitivity pneumonitis and idiopathic pulmonary fibrosis. AB - BACKGROUND: Idiopathic pulmonary fibrosis (IPF), a devastating lung disorder of unknown aetiology, and chronic hypersensitivity pneumonitis (HP), a disease provoked by an immunopathologic reaction to inhaled antigens, are two common interstitial lung diseases with uncertain pathogenic mechanisms. Previously, we have shown in other upper and lower airway diseases that immunoglobulin free light chains (FLCs) are increased and may be involved in initiating a local inflammation. In this study we explored if such a mechanism may also apply to HP and IPF. METHODS: In this study we examined the presence of FLC in serum and BAL fluid from 21 IPF and 22 HP patients and controls. IgG, IgE and tryptase concentrations were measured in BAL fluid only. The presence of FLCs, plasma cells, B cells and mast cells in lung tissue of 3 HP and 3 IPF patients and 1 control was analyzed using immunohistochemistry. RESULTS: FLC concentrations in serum and BAL fluid were increased in IPF and HP patients as compared to control subjects. IgG concentrations were only increased in HP patients, whereas IgE concentrations were comparable to controls in both patient groups. FLC-positive cells, B cells, plasma cells, and large numbers of activated mast cells were all detected in the lungs of HP and IPF patients, not in control lung. CONCLUSION: These results show that FLC concentrations are increased in serum and BAL fluid of IPF and HP patients and that FLCs are present within affected lung tissue. This suggests that FLCs may be involved in mediating pathology in both diseases. PMID- 21980442 TI - Soil biota reduce allelopathic effects of the invasive Eupatorium adenophorum. AB - Allelopathy has been hypothesized to play a role in exotic plant invasions, and study of this process can improve our understanding of how direct and indirect plant interactions influence plant community organization and ecosystem functioning. However, allelopathic effects can be highly conditional. For example allelopathic effects demonstrated in vivo can be difficult to demonstrate in field soils. Here we tested phytotoxicity of Eupatorium adenophorum (croftonweed), one of the most destructive exotic species in China, to a native plant species Brassica rapa both in sand and in native soil. Our results suggested that natural soils from different invaded habitats alleviated or eliminated the efficacy of potential allelochemicals relative to sand cultures. When that soil is sterilized, the allelopathic effects returned; suggesting that soil biota were responsible for the reduced phytotoxicity in natural soils. Neither of the two allelopathic compounds (9-Oxo-10,11-dehydroageraphorone and 9b Hydroxyageraphorone) of E. adenophorum could be found in natural soils infested by the invader, and when those compounds were added to the soils as leachates, they showed substantial degradation after 24 hours in natural soils but not in sand. Our findings emphasize that soil biota can reduce the allelopathic effects of invaders on other plants, and therefore can reduce community invasibility. These results also suggest that soil biota may have stronger or weaker effects on allelopathic interactions depending on how allelochemicals are delivered. PMID- 21980443 TI - MicroRNA regulation and tissue-specific protein interaction network. AB - BACKGROUND: 'Fine-tuning' of protein abundance makes microRNAs (miRNAs) pervasively implicated in human biology. Although targeting many mRNAs endows the power of single miRNA to regulate complex biological processes, its functional roles in a particular tissue will be inevitably restricted because only a subset of its target genes is expressed. METHODS: Here, we analyze the characteristics of miRNA regulation upon target genes according to tissue-specific gene expression by constructing tissue-specific protein interaction networks for ten main types of tissues in the human body. RESULTS: Commonly expressed proteins are under more intensive but lower-cost miRNAs control than proteins with the tissue specific expression. MiRNAs that target more commonly expressed genes usually regulate more tissue-specific genes. This is consistent with the previous finding that tissue-specific proteins tend to be functionally connected with commonly expressed proteins. But to a particular miRNA such a balance is not invariable among different tissues implying diverse tissue regulation modes executed by miRNAs. CONCLUSION: These results suggest miRNAs that interact with more commonly expressed genes can be expected to play important tissue-specific roles. PMID- 21980444 TI - Oral-nasopharyngeal dendritic cells mediate T cell-independent IgA class switching on B-1 B cells. AB - Native cholera toxin (nCT) as a nasal adjuvant was shown to elicit increased levels of T-independent S-IgA antibody (Ab) responses through IL-5- IL-5 receptor interactions between CD4+ T cells and IgA+ B-1 B cells in murine submandibular glands (SMGs) and nasal passages (NPs). Here, we further investigate whether oral nasopharyngeal dendritic cells (DCs) play a central role in the induction of B-1 B cell IgA class switch recombination (CSR) for the enhancement of T cell independent (TI) mucosal S-IgA Ab responses. High expression levels of activation induced cytidine deaminase, Ialpha-CMU circulation transcripts and IMU-Calpha transcripts were seen on B-1 B cells purified from SMGs and NPs of both TCRbeta-/ mice and wild-type mice given nasal trinitrophenyl (TNP)-LPS plus nCT, than in the same tissues of mice given nCT or TNP-LPS alone. Further, DCs from SMGs, NPs and NALT of mice given nasal TNP-LPS plus nCT expressed significantly higher levels of a proliferation-inducing ligand (APRIL) than those in mice given TNP LPS or nCT alone, whereas the B-1 B cells in SMGs and NPs showed elevated levels of transmembrane activator and calcium modulator cyclophilin ligand interactor (TACI) expression. Interestingly, high frequencies of IgA+ B-1 B cells were induced when peritoneal IgA- IgM+ B cells were stimulated with mucosal DCs from mice given nasal TNP-LPS plus nCT. Taken together, these findings show that nasal nCT plays a key role in the enhancement of mucosal DC-mediated TI IgA CSR by B-1 B cells through their interactions with APRIL and TACI. PMID- 21980445 TI - Safety, immunogenicity and dose ranging of a new Vi-CRM197 conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults. AB - BACKGROUND: Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM197) for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM197 in European adults. METHODOLOGY: Following randomized blinded comparison of single vaccination with either Vi CRM197 or licensed polysaccharide vaccines (both containing 25.0 ug of Vi antigen), a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM197 (1.25 ug, 5.0 ug and 12.5 ug of Vi antigen) with the polysaccharide vaccine. PRINCIPAL FINDINGS: All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM197 induced a higher incidence of mild to moderate short lasting local pain. All Vi CRM197 formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship. CONCLUSIONS: Vi-CRM197 did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia. TRIAL REGISTRATION: ClinicalTrials.gov NCT01123941 NCT01193907. PMID- 21980446 TI - Transcriptional profiling of endocrine cerebro-osteodysplasia using microarray and next-generation sequencing. AB - BACKGROUND: Transcriptome profiling of patterns of RNA expression is a powerful approach to identify networks of genes that play a role in disease. To date, most mRNA profiling of tissues has been accomplished using microarrays, but next generation sequencing can offer a richer and more comprehensive picture. METHODOLOGY/PRINCIPAL FINDINGS: ECO is a rare multi-system developmental disorder caused by a homozygous mutation in ICK encoding intestinal cell kinase. We performed gene expression profiling using both cDNA microarrays and next generation mRNA sequencing (mRNA-seq) of skin fibroblasts from ECO-affected subjects. We then validated a subset of differentially expressed transcripts identified by each method using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Finally, we used gene ontology (GO) to identify critical pathways and processes that were abnormal according to each technical platform. Methodologically, mRNA-seq identifies a much larger number of differentially expressed genes with much better correlation to qRT-PCR results than the microarray (r2 = 0.794 and 0.137, respectively). Biologically, cDNA microarray identified functional pathways focused on anatomical structure and development, while the mRNA-seq platform identified a higher proportion of genes involved in cell division and DNA replication pathways. CONCLUSIONS/SIGNIFICANCE: Transcriptome profiling with mRNA-seq had greater sensitivity, range and accuracy than the microarray. The two platforms generated different but complementary hypotheses for further evaluation. PMID- 21980447 TI - Do clonal plants show greater division of labour morphologically and physiologically at higher patch contrasts? AB - BACKGROUND: When growing in reciprocal patches in terms of availability of different resources, connected ramets of clonal plants will specialize to acquire and exchange locally abundant resources more efficiently. This has been termed division of labour. We asked whether division of labour can occur physiologically as well as morphologically and will increase with patch contrasts. METHODOLOGY/PRINCIPAL FINDINGS: We subjected connected and disconnected ramet pairs of Potentilla anserina to Control, Low, Medium and High patch contrast by manipulating light and nutrient levels for ramets in each pair. Little net benefit of inter-ramet connection in terms of biomass was detected. Shoot-root ratio did not differ significantly between paired ramets regardless of connection under Control, Low and Medium. Under High, however, disconnected shaded ramets with ample nutrients showed significantly larger shoot-root ratios (2.8~6.5 fold) than fully-lit but nutrient-deficient ramets, and than their counterparts under any other treatment; conversely, fully-lit but nutrient-deficient ramets, when connected to shaded ramets with ample nutrients, had significantly larger shoot root ratios (2.0~4.9 fold) than the latter and than their counterparts under any other treatment. Only under High patch contrast, fully-lit ramets, if connected to shaded ones, had 8.9% higher chlorophyll content than the latter, and 22.4% higher chlorophyll content than their isolated counterparts; the similar pattern held for photosynthetic capacity under all heterogeneous treatments. CONCLUSIONS/SIGNIFICANCE: Division of labour in clonal plants can be realized by ramet specialization in morphology and in physiology. However, modest ramet specialization especially in morphology among patch contrasts may suggest that division of labour will occur when the connected ramets grow in reciprocal patches between which the contrast exceeds a threshold. Probably, this threshold patch contrast is the outcome of the clone-wide cost-benefit tradeoff and is significant for risk-avoidance, especially in the disturbance-prone environments. PMID- 21980449 TI - Flexibility in animal signals facilitates adaptation to rapidly changing environments. AB - Charles Darwin posited that secondary sexual characteristics result from competition to attract mates. In male songbirds, specialized vocalizations represent secondary sexual characteristics of particular importance because females prefer songs at specific frequencies, amplitudes, and duration. For birds living in human-dominated landscapes, historic selection for song characteristics that convey fitness may compete with novel selective pressures from anthropogenic noise. Here we show that black-capped chickadees (Poecile atricapillus) use shorter, higher-frequency songs when traffic noise is high, and longer, lower frequency songs when noise abates. We suggest that chickadees balance opposing selective pressures by use low-frequency songs to preserve vocal characteristics of dominance that repel competitors and attract females, and high frequency songs to increase song transmission when their environment is noisy. The remarkable vocal flexibility exhibited by chickadees may be one reason that they thrive in urban environments, and such flexibility may also support subsequent genetic adaptation to an increasingly urbanized world. PMID- 21980448 TI - Autocrine netrin function inhibits glioma cell motility and promotes focal adhesion formation. AB - Deregulation of mechanisms that control cell motility plays a key role in tumor progression by promoting tumor cell dissemination. Secreted netrins and their receptors, Deleted in Colorectal Cancer (DCC), neogenin, and the UNC5 homologues, regulate cell and axon migration, cell adhesion, and tissue morphogenesis. Netrin and netrin receptor expression have previously been shown to be disrupted in invasive tumors, including glioblastoma. We determined that the human glioblastoma cell lines U87, U343, and U373 all express neogenin, UNC5 homologues, and netrin-1 or netrin-3, but only U87 cells express DCC. Using transfilter migration assays, we demonstrate DCC-dependent chemoattractant migration of U87 cells up a gradient of netrin-1. In contrast, U343 and U373 cells, which do not express DCC, were neither attracted nor repelled. Ectopic expression of DCC by U343 and U373 cells resulted in these cells becoming competent to respond to a gradient of netrin-1 as a chemoattractant, and also slowed their rate of spontaneous migration. Here, in addition to netrins' well characterized chemotropic activity, we demonstrate an autocrine function for netrin-1 and netrin-3 in U87 and U373 cells that slows migration. We provide evidence that netrins promote the maturation of focal complexes, structures associated with cell movement, into focal adhesions. Consistent with this, netrin, DCC, and UNC5 homologues were associated with focal adhesions, but not focal complexes. Disrupting netrin or DCC function did not alter cell proliferation or survival. Our findings provide evidence that DCC can slow cell migration, and that neogenin and UNC5 homologues are not sufficient to substitute for DCC function in these cells. Furthermore, we identify a role for netrins as autocrine inhibitors of cell motility that promote focal adhesion formation. These findings suggest that disruption of netrin signalling may disable a mechanism that normally restrains inappropriate cell migration. PMID- 21980450 TI - Intracerebral administration of recombinant rabies virus expressing GM-CSF prevents the development of rabies after infection with street virus. AB - Recently it was found that prior immunization with recombinant rabies virus (RABV) expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) (LBNSE-GM-CSF) resulted in high innate/adaptive immune responses and protection against challenge with virulent RABV (Wen et al., JVI, 2011). In this study, the ability of LBNSE-GM-CSF to prevent animals from developing rabies was investigated in mice after infection with lethal doses of street RABV. It was found that intracerebral administration of LBNSE-GM-CSF protected more mice from developing rabies than sham-treated mice as late as day 5 after infection with street RABV. Intracerebral administration of LBNSE-GM-CSF resulted in significantly higher levels of chemokine/cytokine expression and more infiltration of inflammatory and immune cells into the central nervous system (CNS) than sham-administration or administration with UV-inactivated LBNSE-GM CSF. Enhancement of blood-brain barrier (BBB) permeability and increases in virus neutralizing antibodies (VNA) were also observed in mice treated with LBNSE-GM CSF. On the other hand, intracerebral administration with UV-inactivated LBNSE-GM CSF did not increase protection despite the fact that VNA were induced in the periphery. However, intracerebral administration with chemoattractant protein-1 (MCP-1, also termed CCL2) increased significantly the protective efficacy of UV inactivated LBNSE-GM-CSF. Together these studies confirm that direct administration of LBNSE-GM-CSF can enhance the innate and adaptive immunity as well as the BBB permeability, thus allowing infiltration of inflammatory cells and other immune effectors enter into the CNS to clear the virus and prevent the development of rabies. PMID- 21980452 TI - An alpha/beta hydrolase and associated Per-ARNT-Sim domain comprise a bipartite sensing module coupled with diverse output domains. AB - The RsbQ alpha/beta hydrolase and RsbP serine phosphatase form a signaling pair required to activate the general stress factor sigma(B) of Bacillus subtilis in response to energy limitation. RsbP has a predicted N-terminal Per-ARNT-Sim (PAS) domain, a central coiled-coil, and a C-terminal protein phosphatase M (PPM) domain. Previous studies support a model in which RsbQ provides an activity needed for PAS to regulate the phosphatase domain via the coiled-coil. RsbQ and the PAS domain (RsbP-PAS) therefore appear to form a sensory module. Here we test this hypothesis using bioinformatic and genetic analysis. We found 45 RsbQ and RsbP-PAS homologues encoded by adjacent genes in diverse bacteria, with PAS and a predicted coiled-coil fused to one of three output domains: PPM phosphatase (Gram positive bacteria), histidine protein kinase (Gram negative bacteria), and diguanylate cyclase (both lineages). Multiple alignment of the RsbP-PAS homologues suggested nine residues that distinguish the class. Alanine substitutions at four of these conferred a null phenotype in B. subtilis, indicating their functional importance. The F55A null substitution lay in the Falpha helix of an RsbP-PAS model. F55A inhibited interaction of RsbP with RsbQ in yeast two-hybrid and pull-down assays but did not significantly affect interaction of RsbP with itself. We propose that RsbQ directly contacts the PAS domains of an RsbP oligomer to provide the activating signal, which is propagated to the phosphatase domains via the coiled-coil. A similar mechanism would allow the RsbQ-PAS module to convey a common input signal to structurally diverse output domains, controlling a variety of physiological responses. PMID- 21980451 TI - Inducing autophagy by rapamycin before, but not after, the formation of plaques and tangles ameliorates cognitive deficits. AB - Previous studies have shown that inducing autophagy ameliorates early cognitive deficits associated with the build-up of soluble amyloid-beta (Abeta). However, the effects of inducing autophagy on plaques and tangles are yet to be determined. While soluble Abeta and tau represent toxic species in Alzheimer's disease (AD) pathogenesis, there is well documented evidence that plaques and tangles also are detrimental to normal brain function. Thus, it is critical to assess the effects of inducing autophagy in an animal model with established plaques and tangles. Here we show that rapamycin, when given prophylactically to 2-month-old 3xTg-AD mice throughout their life, induces autophagy and significantly reduces plaques, tangles and cognitive deficits. In contrast, inducing autophagy in 15-month-old 3xTg-AD mice, which have established plaques and tangles, has no effects on AD-like pathology and cognitive deficits. In conclusion, we show that autophagy induction via rapamycin may represent a valid therapeutic strategy in AD when administered early in the disease progression. PMID- 21980453 TI - Co-interactive DNA-binding between a novel, immunophilin-like shrimp protein and VP15 nucleocapsid protein of white spot syndrome virus. AB - White spot syndrome virus (WSSV) is one of the most serious pathogens of penaeid shrimp. Although its genome has been completely characterized, the functions of most of its putative proteins are not yet known. It has been suggested that the major nucleocapsid protein VP15 is involved in packaging of the WSSV genome during virion formation. However, little is known in its relationship with shrimp host cells. Using the yeast two-hybrid approach to screen a shrimp lymphoid organ (LO) cDNA library for proteins that might interact with VP15, a protein named PmFKBP46 was identified. It had high sequence similarity to a 46 kDa-immunophilin called FKBP46 from the lepidopteran Spodoptera frugiperda (the fall armyworm). The full length PmFKBP46 consisted of a 1,257-nucleotide open reading frame with a deduced amino acid sequence of 418 residues containing a putative FKBP-PPIase domain in the C-terminal region. Results from a GST pull-down assay and histological co-localization revealed that VP15 physically interacted with PmFKBP46 and that both proteins shared the same subcellular location in the nucleus. An electrophoretic mobility shift assay indicated that PmFKBP46 possessed DNA-binding activity and functionally co-interacted with VP15 in DNA binding. The overall results suggested that host PmFKBP46 might be involved in genome packaging by viral VP15 during virion assembly. PMID- 21980454 TI - Altered topological properties of functional network connectivity in schizophrenia during resting state: a small-world brain network study. AB - Aberrant topological properties of small-world human brain networks in patients with schizophrenia (SZ) have been documented in previous neuroimaging studies. Aberrant functional network connectivity (FNC, temporal relationships among independent component time courses) has also been found in SZ by a previous resting state functional magnetic resonance imaging (fMRI) study. However, no study has yet determined if topological properties of FNC are also altered in SZ. In this study, small-world network metrics of FNC during the resting state were examined in both healthy controls (HCs) and SZ subjects. FMRI data were obtained from 19 HCs and 19 SZ. Brain images were decomposed into independent components (ICs) by group independent component analysis (ICA). FNC maps were constructed via a partial correlation analysis of ICA time courses. A set of undirected graphs were built by thresholding the FNC maps and the small-world network metrics of these maps were evaluated. Our results demonstrated significantly altered topological properties of FNC in SZ relative to controls. In addition, topological measures of many ICs involving frontal, parietal, occipital and cerebellar areas were altered in SZ relative to controls. Specifically, topological measures of whole network and specific components in SZ were correlated with scores on the negative symptom scale of the Positive and Negative Symptom Scale (PANSS). These findings suggest that aberrant architecture of small world brain topology in SZ consists of ICA temporally coherent brain networks. PMID- 21980455 TI - Wolbachia-mediated antibacterial protection and immune gene regulation in Drosophila. AB - The outcome of microbial infection of insects is dependent not only on interactions between the host and pathogen, but also on the interactions between microbes that co-infect the host. Recently the maternally inherited endosymbiotic bacteria Wolbachia has been shown to protect insects from a range of microbial and eukaryotic pathogens. Mosquitoes experimentally infected with Wolbachia have upregulated immune responses and are protected from a number of pathogens including viruses, bacteria, Plasmodium and filarial nematodes. It has been hypothesised that immune upregulation underpins Wolbachia-mediated protection. Drosophila is a strong model for understanding host-Wolbachia-pathogen interactions. Wolbachia-mediated antiviral protection in Drosophila has been demonstrated for a number of different Wolbachia strains. In this study we investigate whether Wolbachia-infected flies are also protected against pathogenic bacteria. Drosophila simulans lines infected with five different Wolbachia strains were challenged with the pathogenic bacteria Pseudomonas aeruginosa PA01, Serratia marcescens and Erwinia carotovora and mortality compared to paired lines without Wolbachia. No difference in mortality was observed in the flies with or without Wolbachia. Similarly no antibacterial protection was observed for D. melanogaster infected with Wolbachia. Interestingly, D. melanogaster Oregon RC flies which are naturally infected with Wolbachia showed no upregulation of the antibacterial immune genes TepIV, Defensin, Diptericin B, PGRP-SD, Cecropin A1 and Attacin D compared to paired flies without Wolbachia. Taken together these results indicate that Wolbachia mediated antibacterial protection is not ubiquitous in insects and furthermore that the mechanisms of antibacterial and antiviral protection are independent. We suggest that the immune priming and antibacterial protection observed in Wolbachia-infected mosquitoes may be a consequence of the recent artificial introduction of the symbiont into insects that normally do not carry Wolbachia and that antibacterial protection is unlikely to be found in insects carrying long-term Wolbachia infections. PMID- 21980457 TI - Multiscale analyses of mammal species composition--environment relationship in the contiguous USA. AB - Relationships between species composition and its environmental determinants are a basic objective of ecology. Such relationships are scale dependent, and predictors of species composition typically include variables such as climate, topographic, historical legacies, land uses, human population levels, and random processes. Our objective was to quantify the effect of environmental determinants on U.S. mammal composition at various spatial scales. We found that climate was the predominant factor affecting species composition, and its relative impact increased in correlation with the increase of the spatial scale. Another factor affecting species composition is land-use-land-cover. Our findings showed that its impact decreased as the spatial scale increased. We provide quantitative indication of highly significant effect of climate and land-use-land-cover variables on mammal composition at multiple scales. PMID- 21980456 TI - Activation of AMP-activated protein kinase is required for berberine-induced reduction of atherosclerosis in mice: the role of uncoupling protein 2. AB - AIMS: Berberine, a botanical alkaloid purified from Coptidis rhizoma, is reported to activate the AMP-activated protein kinase (AMPK). Whether AMPK is required for the protective effects of berberine in cardiovascular diseases remains unknown. This study was designed to determine whether AMPK is required for berberine induced reduction of oxidative stress and atherosclerosis in vivo. METHODS: ApoE (ApoE-/-) mice and ApoE-/-/AMPK alpha 2-/- mice that were fed Western diets were treated with berberine for 8 weeks. Atherosclerotic aortic lesions, expression of uncoupling protein 2 (UCP2), and markers of oxidative stress were evaluated in isolated aortas. RESULTS: In ApoE-/- mice, chronic administration of berberine significantly reduced aortic lesions, markedly reduced oxidative stress and expression of adhesion molecules in aorta, and significantly increased UCP2 levels. In contrast, in ApoE-/-/AMPK alpha 2-/- mice, berberine had little effect on those endpoints. In cultured human umbilical vein endothelial cells (HUVECs), berberine significantly increased UCP2 mRNA and protein expression in an AMPK dependent manner. Transfection of HUVECs with nuclear respiratory factor 1 (NRF1) specific siRNA attenuated berberine-induced expression of UCP2, whereas transfection with control siRNA did not. Finally, berberine promoted mitochondrial biogenesis that contributed to up-regulation of UCP2 expression. CONCLUSION: We conclude that berberine reduces oxidative stress and vascular inflammation, and suppresses atherogenesis via a mechanism that includes stimulation of AMPK-dependent UCP2 expression. PMID- 21980458 TI - Interleukin-1 receptor antagonist modulates the early phase of liver regeneration after partial hepatectomy in mice. AB - BACKGROUND: Cytokine administration is a potential therapy for acute liver failure by reducing inflammatory responses and favour hepatocyte regeneration. The aim of this study was to evaluate the role of interleukin-1 receptor antagonist (IL-1ra) during liver regeneration and to study the effect of a recombinant human IL-1ra on liver regeneration. METHODS: We performed 70% hepatectomy in wild type (WT) mice, IL-1ra knock-out (KO) mice and in WT mice treated by anakinra. We analyzed liver regeneration at regular intervals by measuring the blood levels of cytokines, the hepatocyte proliferation by bromodeoxyuridin (BrdU) incorporation, proliferating cell nuclear antigen (PCNA) and Cyclin D1 expression. The effect of anakinra on hepatocyte proliferation was also tested in vitro using human hepatocytes. RESULTS: At 24h and at 48 h after hepatectomy, IL-1ra KO mice had significantly higher levels of pro-inflammatory cytokines (IL-6, IL-1beta and MCP-1) and a reduced and delayed hepatocyte proliferation measured by BrdU incorporation, PCNA and Cyclin D1 protein levels, when compared to WT mice. IGFBP-1 and C/EBPbeta expression was significantly decreased in IL-1ra KO compared to WT mice. WT mice treated with anakinra showed significantly decreased levels of IL-6 and significantly higher hepatocyte proliferation at 24h compared to untreated WT mice. In vitro, primary human hepatocytes treated with anakinra showed significantly higher proliferation at 24h compared to hepatocytes without treatment. CONCLUSION: IL1ra modulates the early phase of liver regeneration by decreasing the inflammatory stress and accelerating the entry of hepatocytes in proliferation. IL1ra might be a therapeutic target to improve hepatocyte proliferation. PMID- 21980459 TI - How much does it cost to expand a protected area system? Some critical determining factors and ranges of costs for Queensland. AB - Many governments have recently gone on record promising large-scale expansions of protected areas to meet global commitments such as the Convention on Biological Diversity. As systems of protected areas are expanded to be more comprehensive, they are more likely to be implemented if planners have realistic budget estimates so that appropriate funding can be requested. Estimating financial budgets a priori must acknowledge the inherent uncertainties and assumptions associated with key parameters, so planners should recognize these uncertainties by estimating ranges of potential costs. We explore the challenge of budgeting a priori for protected area expansion in the face of uncertainty, specifically considering the future expansion of protected areas in Queensland, Australia. The government has committed to adding ~12 million ha to the reserve system, bringing the total area protected to 20 million ha by 2020. We used Marxan to estimate the costs of potential reserve designs with data on actual land value, market value, transaction costs, and land tenure. With scenarios, we explored three sources of budget variability: size of biodiversity objectives; subdivision of properties; and legal acquisition routes varying with tenure. Depending on the assumptions made, our budget estimates ranged from $214 million to $2.9 billion. Estimates were most sensitive to assumptions made about legal acquisition routes for leasehold land. Unexpected costs (costs encountered by planners when real-world costs deviate from assumed costs) responded non-linearly to inability to subdivide and percentage purchase of private land. A financially conservative approach--one that safeguards against large cost increases while allowing for potential financial windfalls--would involve less optimistic assumptions about acquisition and subdivision to allow Marxan to avoid expensive properties where possible while meeting conservation objectives. We demonstrate how a rigorous analysis can inform discussions about the expansion of systems of protected areas, including the identification of factors that influence budget variability. PMID- 21980460 TI - Gestational exposure to low dose bisphenol A alters social behavior in juvenile mice. AB - Bisphenol A (BPA) is a man-made compound used to make polycarbonate plastics and epoxy resins; public health concerns have been fueled by findings that BPA exposure can reduce sex differences in brain and some behaviors. We asked if a low BPA dose, within the range measured in humans, ingested during pregnancy, would affect social behaviors in prepubertal mice. We noted sex differences in social interactions whereby females spent more time sitting side-by-side, while males engaged in more exploring and sitting alone. In addition BPA increased display of nose-to-nose contacts, play solicitations and approaches in both sexes. Interactions between sex and diet were found for self grooming, social interactions while sitting side-by-side and following the other mouse. In all these cases interactions were produced by differences between control and BPA females. We examined brains from embryos during late gestation to determine if gene expression differences might be correlated with some of the sexually dimorphic or BPA affected behaviors we observed. Because BPA treatments ended at birth we took the brains during embryogenesis to increase the probability of discovering BPA mediated effects. We also selected this embryonic age (E18.5) because it coincides with the onset of sexual differentiation of the brain. Interestingly, mRNA for the glutamate transporter, Slc1a1, was enhanced by exposure to BPA in female brains. Also we noted that BPA changed the expression of two of the three DNA methyltransferase genes, Dnmt1 and Dnmt3a. We propose that BPA affects DNA methylation of Sc1a1 during neural development. Sex differences in juvenile social interactions are affected by BPA and in particular this compound modifies behavior in females. PMID- 21980461 TI - Activation of WNT/beta-catenin signaling in pulmonary fibroblasts by TGF-beta1 is increased in chronic obstructive pulmonary disease. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by abnormal extracellular matrix (ECM) turnover. Recently, activation of the WNT/beta-catenin pathway has been associated with abnormal ECM turnover in various chronic diseases. We determined WNT-pathway gene expression in pulmonary fibroblasts of individuals with and without COPD and disentangled the role of beta-catenin in fibroblast phenotype and function. METHODS: We assessed the expression of WNT-pathway genes and the functional role of beta-catenin, using MRC-5 human lung fibroblasts and primary pulmonary fibroblasts of individuals with and without COPD. RESULTS: Pulmonary fibroblasts expressed mRNA of genes required for WNT signaling. Stimulation of fibroblasts with TGF-beta1, a growth factor important in COPD pathogenesis, induced WNT-5B, FZD8, DVL3 and beta catenin mRNA expression. The induction of WNT-5B, FZD6, FZD8 and DVL3 mRNA by TGF beta1 was higher in fibroblasts of individuals with COPD than without COPD, whilst basal expression was similar. Accordingly, TGF-beta1 activated beta catenin signaling, as shown by an increase in transcriptionally active and total beta-catenin protein expression. Furthermore, TGF-beta1induced the expression of collagen1alpha1, alpha-sm-actin and fibronectin, which was attenuated by beta catenin specific siRNA and by pharmacological inhibition of beta-catenin, whereas the TGF-beta1-induced expression of PAI-1 was not affected. The induction of transcriptionally active beta-catenin and subsequent fibronectin deposition induced by TGF-beta1 were enhanced in pulmonary fibroblasts from individuals with COPD. CONCLUSIONS: beta-catenin signaling contributes to ECM production by pulmonary fibroblasts and contributes to myofibroblasts differentiation. WNT/beta catenin pathway expression and activation by TGF-beta1 is enhanced in pulmonary fibroblasts from individuals with COPD. This suggests an important role of the WNT/beta-catenin pathway in regulating fibroblast phenotype and function in COPD. PMID- 21980462 TI - miR-18a impairs DNA damage response through downregulation of ataxia telangiectasia mutated (ATM) kinase. AB - The DNA damage response (DDR) encompasses multi-step processes by which cells evolve to sense DNA damage, transduce the signal and initiate the repair of damaged DNA. Ataxia Telangiectasia Mutated (ATM) Kinase, which functions as the primary sensor and transducer of DNA damage signal, has been demonstrated to play an important role in the DDR and cancer prevention. Hence, understanding the molecular mechanisms underlying the regulation of ATM has received much attention. Here, we found that miR-18a was upregulated in both cell lines and patients' tissue samples of breast cancer. Furthermore, we demonstrated that ectopically expressing miR-18a downregulated ATM expression by directly targeting the ATM-3'-UTR and abrogated the IR-induced cell cycle arrest. Similar to the effect of ATM siRNA, overexpressing miR-18a in breast cancer cells reduced the DNA damage repair ability and the efficiency of homologous recombination-based DNA repair (HRR) and sensitized cells to gamma-irradiation (IR) treatment. However, inhibition of miR-18a led to augmentation of DNA damage repair, increase of HRR efficiency and reduced cellular radiosensitivity. Moreover, we showed that the phorsphorylation level and nuclear foci formation of H2AX and 53BP1, the downstream substrates of ATM kinase, were significantly deceased in miR-18a overexpressing cells. Taken together, our results uncover a new regulatory mechanism of ATM expression and suggest that miR-18a might be a novel therapeutic target. PMID- 21980463 TI - Bisphenol A and 17beta-estradiol promote arrhythmia in the female heart via alteration of calcium handling. AB - BACKGROUND: There is wide-spread human exposure to bisphenol A (BPA), a ubiquitous estrogenic endocrine disruptor that has been implicated as having potentially harmful effects on human heart health. Higher urine BPA concentrations have been shown to be associated with cardiovascular diseases in humans. However, neither the nature nor the mechanism(s) of BPA action on the heart are understood. METHODOLOGY/PRINCIPAL FINDINGS: The rapid (<7 min) effects of BPA and 17beta-estradiol (E2) in the heart and ventricular myocytes from rodents were investigated in the present study. In isolated ventricular myocytes from young adult females, but not males, physiological concentrations of BPA or E2 (10-9 M) rapidly induced arrhythmogenic triggered activities. The effects of BPA were particularly pronounced when combined with estradiol. Under conditions of catecholamine stimulation, E2 and BPA promoted ventricular arrhythmias in female, but not male, hearts. The cellular mechanism of the female-specific pro arrhythmic effects of BPA and E2 were investigated. Exposure to E2 and/or BPA rapidly altered myocyte Ca2+ handling; in particular, estrogens markedly increased sarcoplasmic reticulum (SR) Ca2+ leak, and increased SR Ca2+ load. Ryanodine (10-7 M) inhibition of SR Ca2+ leak suppressed estrogen-induced triggered activities. The rapid response of female myocytes to estrogens was abolished in an estrogen receptor (ER) beta knockout mouse model. CONCLUSIONS/SIGNIFICANCE: Physiologically-relevant concentrations of BPA and E2 promote arrhythmias in a female-specific manner in rat hearts; the pro-arrhythmic actions of estrogens are mediated by ERbeta-signaling through alterations of myocyte Ca2+ handling, particularly increases in SR Ca2+ leak. Our study provides the first experimental evidence suggesting that exposure to estrogenic endocrine disrupting chemicals and the unique sensitivity of female hearts to estrogens may play a role in arrhythmogenesis in the female heart. PMID- 21980464 TI - Biophysical characteristics reveal neural stem cell differentiation potential. AB - BACKGROUND: Distinguishing human neural stem/progenitor cell (huNSPC) populations that will predominantly generate neurons from those that produce glia is currently hampered by a lack of sufficient cell type-specific surface markers predictive of fate potential. This limits investigation of lineage-biased progenitors and their potential use as therapeutic agents. A live-cell biophysical and label-free measure of fate potential would solve this problem by obviating the need for specific cell surface markers. METHODOLOGY/PRINCIPAL FINDINGS: We used dielectrophoresis (DEP) to analyze the biophysical, specifically electrophysiological, properties of cortical human and mouse NSPCs that vary in differentiation potential. Our data demonstrate that the electrophysiological property membrane capacitance inversely correlates with the neurogenic potential of NSPCs. Furthermore, as huNSPCs are continually passaged they decrease neuron generation and increase membrane capacitance, confirming that this parameter dynamically predicts and negatively correlates with neurogenic potential. In contrast, differences in membrane conductance between NSPCs do not consistently correlate with the ability of the cells to generate neurons. DEP crossover frequency, which is a quantitative measure of cell behavior in DEP, directly correlates with neuron generation of NSPCs, indicating a potential mechanism to separate stem cells biased to particular differentiated cell fates. CONCLUSIONS/SIGNIFICANCE: We show here that whole cell membrane capacitance, but not membrane conductance, reflects and predicts the neurogenic potential of human and mouse NSPCs. Stem cell biophysical characteristics therefore provide a completely novel and quantitative measure of stem cell fate potential and a label-free means to identify neuron- or glial-biased progenitors. PMID- 21980465 TI - Nano-stenciled RGD-gold patterns that inhibit focal contact maturation induce lamellipodia formation in fibroblasts. AB - Cultured fibroblasts adhere to extracellular substrates by means of cell-matrix adhesions that are assembled in a hierarchical way, thereby gaining in protein complexity and size. Here we asked how restricting the size of cell-matrix adhesions affects cell morphology and behavior. Using a nanostencil technique, culture substrates were patterned with gold squares of a width and spacing between 250 nm and 2 um. The gold was functionalized with RGD peptide as ligand for cellular integrins, and mouse embryo fibroblasts were plated. Limiting the length of cell-matrix adhesions to 500 nm or less disturbed the maturation of vinculin-positive focal complexes into focal contacts and fibrillar adhesions, as indicated by poor recruitment of alpha5-integrin. We found that on sub-micrometer patterns, fibroblasts spread extensively, but did not polarize. Instead, they formed excessive numbers of lamellipodia and a fine actin meshwork without stress fibers. Moreover, these cells showed aberrant fibronectin fibrillogenesis, and their speed of directed migration was reduced significantly compared to fibroblasts on 2 um square patterns. Interference with RhoA/ROCK signaling eliminated the pattern-dependent differences in cell morphology. Our results indicate that manipulating the maturation of cell-matrix adhesions by nanopatterned surfaces allows to influence morphology, actin dynamics, migration and ECM assembly of adhering fibroblasts. PMID- 21980466 TI - Control of vocal and respiratory patterns in birdsong: dissection of forebrain and brainstem mechanisms using temperature. AB - Learned motor behaviors require descending forebrain control to be coordinated with midbrain and brainstem motor systems. In songbirds, such as the zebra finch, regular breathing is controlled by brainstem centers, but when the adult songbird begins to sing, its breathing becomes tightly coordinated with forebrain controlled vocalizations. The periods of silence (gaps) between song syllables are typically filled with brief breaths, allowing the bird to sing uninterrupted for many seconds. While substantial progress has been made in identifying the brain areas and pathways involved in vocal and respiratory control, it is not understood how respiratory and vocal control is coordinated by forebrain motor circuits. Here we combine a recently developed technique for localized brain cooling, together with recordings of thoracic air sac pressure, to examine the role of cortical premotor nucleus HVC (proper name) in respiratory-vocal coordination. We found that HVC cooling, in addition to slowing all song timescales as previously reported, also increased the duration of expiratory pulses (EPs) and inspiratory pulses (IPs). Expiratory pulses, like song syllables, were stretched uniformly by HVC cooling, but most inspiratory pulses exhibited non-uniform stretch of pressure waveform such that the majority of stretch occurred late in the IP. Indeed, some IPs appeared to change duration by the earlier or later truncation of an underlying inspiratory event. These findings are consistent with the idea that during singing the temporal structure of EPs is under the direct control of forebrain circuits, whereas that of IPs can be strongly influenced by circuits downstream of HVC, likely in the brainstem. An analysis of the temporal jitter of respiratory and vocal structure suggests that IPs may be initiated by HVC at the end of each syllable and terminated by HVC immediately before the onset of the next syllable. PMID- 21980467 TI - Electrospun PLLA nanofiber scaffolds and their use in combination with BMP-2 for reconstruction of bone defects. AB - INTRODUCTION: Adequate migration and differentiation of mesenchymal stem cells is essential for regeneration of large bone defects. To achieve this, modern graft materials are becoming increasingly important. Among them, electrospun nanofiber scaffolds are a promising approach, because of their high physical porosity and potential to mimic the extracellular matrix (ECM). MATERIALS AND METHODS: The objective of the present study was to examine the impact of electrospun PLLA nanofiber scaffolds on bone formation in vivo, using a critical size rat calvarial defect model. In addition we analyzed whether direct incorporation of bone morphogenetic protein 2 (BMP-2) into nanofibers could enhance the osteoinductivity of the scaffolds. Two critical size calvarial defects (5 mm) were created in the parietal bones of adult male Sprague-Dawley rats. Defects were either (1) left unfilled, or treated with (2) bovine spongiosa, (3) PLLA scaffolds alone or (4) PLLA/BMP-2 scaffolds. Cranial CT-scans were taken at fixed intervals in vivo. Specimens obtained after euthanasia were processed for histology, histomorphometry and immunostaining (Osteocalcin, BMP-2 and Smad5). RESULTS: PLLA scaffolds were well colonized with cells after implantation, but only showed marginal ossification. PLLA/BMP-2 scaffolds showed much better bone regeneration and several ossification foci were observed throughout the defect. PLLA/BMP-2 scaffolds also stimulated significantly faster bone regeneration during the first eight weeks compared to bovine spongiosa. However, no significant differences between these two scaffolds could be observed after twelve weeks. Expression of osteogenic marker proteins in PLLA/BMP-2 scaffolds continuously increased throughout the observation period. After twelve weeks osteocalcin, BMP-2 and Smad5 were all significantly higher in the PLLA/BMP-2 group than in all other groups. CONCLUSION: Electrospun PLLA nanofibers facilitate colonization of bone defects, while their use in combination with BMP 2 also increases bone regeneration in vivo and thus combines osteoconductivity of the scaffold with the ability to maintain an adequate osteogenic stimulus. PMID- 21980469 TI - siRNAs induce efficient RNAi response in Bombyx mori embryos. AB - Short interference RNA (siRNA) is widely used in mammalian cells. In insects, however, reports concerning the suitablility of siRNA in vivo is very limited compared with that of long dsRNA, which is thought to be more effective. There is insufficient information on the essential rules of siRNA design in insects, as very few siRNAs have been tested in this context. To establish an effective method of gene silencing using siRNA in vivo in insects, we determined the effects of siRNA on seven target genes. We designed siRNAs according to a new guideline and injected them into eggs of Bombyx mori. At the mRNA level, the expression of most of these genes was successfully silenced, down to less than half the constitutive level, which in some cases led to the development of distinctive phenotypes. In addition, we observed stronger effect of siRNA both on the mRNA level and the phenotype than that of long dsRNA under comparable conditions. These results indicate that direct injection of siRNA is an effective reverse-genetics tool for the analysis of embryogenesis in vivo in insects. PMID- 21980468 TI - Deficiency of mDia, an actin nucleator, disrupts integrity of neuroepithelium and causes periventricular dysplasia. AB - During development of the central nervous system, the apical-basal polarity of neuroepithelial cells is critical for homeostasis of proliferation and differentiation of neural stem cells. While adherens junctions at the apical surface of neuroepithelial cells are important for maintaining the polarity, the molecular mechanism regulating integrity of these adherens junctions remains largely unknown. Given the importance of actin cytoskeleton in adherens junctions, we have analyzed the role of mDia, an actin nucleator and a Rho effector, in the integrity of the apical adherens junction. Here we show that mDia1 and mDia3 are expressed in the developing brain, and that mDia3 is concentrated in the apical surface of neuroepithelium. Mice deficient in both mDia1 and mDia3 develop periventricular dysplastic mass widespread throughout the developing brain, where neuroepithelial cell polarity is impaired with attenuated apical actin belts and loss of apical adherens junctions. In addition, electron microscopic analysis revealed abnormal shrinkage and apical membrane bulging of neuroepithelial cells in the remaining areas. Furthermore, perturbation of Rho, but not that of ROCK, causes loss of the apical actin belt and adherens junctions similarly to mDia-deficient mice. These results suggest that actin cytoskeleton regulated by Rho-mDia pathway is critical for the integrity of the adherens junctions and the polarity of neuroepithelial cells, and that loss of this signaling induces aberrant, ectopic proliferation and differentiation of neural stem cells. PMID- 21980471 TI - Low and high expressing alleles of the LMNA gene: implications for laminopathy disease development. AB - Today, there are at least a dozen different genetic disorders caused by mutations within the LMNA gene, and collectively, they are named laminopathies. Interestingly, the same mutation can cause phenotypes with different severities or even different disorders and might, in some cases, be asymptomatic. We hypothesized that one possible contributing mechanism for this phenotypic variability could be the existence of high and low expressing alleles in the LMNA locus. To investigate this hypothesis, we developed an allele-specific absolute quantification method for lamin A and lamin C transcripts using the polymorphic rs4641(C/T)LMNA coding SNP. The contribution of each allele to the total transcript level was investigated in nine informative human primary dermal fibroblast cultures from Hutchinson-Gilford progeria syndrome (HGPS) and unaffected controls. Our results show differential expression of the two alleles. The C allele is more frequently expressed and accounts for ~70% of the lamin A and lamin C transcripts. Analysis of samples from six patients with Hutchinson Gilford progeria syndrome showed that the c.1824C>T, p.G608G mutation is located in both the C and the T allele, which might account for the variability in phenotype seen among HGPS patients. Our method should be useful for further studies of human samples with mutations in the LMNA gene and to increase the understanding of the link between genotype and phenotype in laminopathies. PMID- 21980470 TI - Identification of a variable number of tandem repeats polymorphism and characterization of LEF-1 response elements in the promoter of the IDO1 gene. AB - BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) catalyzes the first and rate limiting step of the kynurenine pathway that is an important component of immunomodulatory and neuromodulatory processes. The IDO1 gene is highly inducible by IFN-gamma and TNF-alpha through interaction with cis-acting regulatory elements of the promoter region. Accordingly, functional polymorphisms in the IDO1 promoter could partly explain the interindividual variability in IDO expression that has been previously documented. METHODOLOGY/PRINCIPAL FINDINGS: A PCR-sequencing strategy, applied to DNA samples from healthy Caucasians, allowed us to identify a VNTR polymorphism in the IDO1 promoter, which correlates significantly with serum tryptophan concentration, controlled partially by IDO activity, in female subjects, but not in males. Although this VNTR does not appear to affect basal or cytokine-induced promoter activity in gene reporter assays, it contains novel cis-acting elements. Three putative LEF-1 binding sites, one being located within the VNTR repeat motif, were predicted in silico and confirmed by chromatin immunoprecipitation. Overexpression of LEF-1 in luciferase assays confirmed an interaction between LEF-1 and the predicted transcription factor binding sites, and modification of the LEF-1 core sequence within the VNTR repeat motif, by site-directed mutagenesis, resulted in an increase in promoter activity. CONCLUSIONS/SIGNIFICANCE: The identification of a VNTR in the IDO1 promoter revealed a cis-acting element interacting with the most downstream factor of the Wnt signaling pathway, suggesting novel mechanisms of regulation of IDO1 expression. These data offer new insights, and suggest further studies, into the role of IDO in various pathological conditions, particularly in cancer where IDO and the Wnt pathway are strongly dysregulated. PMID- 21980472 TI - Distinct temporal and anatomical distributions of amyloid-beta and tau abnormalities following controlled cortical impact in transgenic mice. AB - Traumatic brain injury (TBI) is a major environmental risk factor for Alzheimer's disease. Intracellular accumulations of amyloid-beta and tau proteins have been observed within hours following severe TBI in humans. Similar abnormalities have been recapitulated in young 3xTg-AD mice subjected to the controlled cortical impact model (CCI) of TBI and sacrificed at 24 h and 7 days post injury. This study investigated the temporal and anatomical distributions of amyloid-beta and tau abnormalities from 1 h to 24 h post injury in the same model. Intra-axonal amyloid-beta accumulation in the fimbria was detected as early as 1 hour and increased monotonically over 24 hours following injury. Tau immunoreactivity in the fimbria and amygdala had a biphasic time course with peaks at 1 hour and 24 hours, while tau immunoreactivity in the contralateral CA1 rose in a delayed fashion starting at 12 hours after injury. Furthermore, rapid intra-axonal amyloid-beta accumulation was similarly observed post controlled cortical injury in APP/PS1 mice, another transgenic Alzheimer's disease mouse model. Acute increases in total and phospho-tau immunoreactivity were also evident in single transgenic Tau(P301L) mice subjected to controlled cortical injury. These data provide further evidence for the causal effects of moderately severe contusional TBI on acceleration of acute Alzheimer-related abnormalities and the independent relationship between amyloid-beta and tau in this setting. PMID- 21980473 TI - HIF-1 and SKN-1 coordinate the transcriptional response to hydrogen sulfide in Caenorhabditis elegans. AB - Hydrogen sulfide (H2S) has dramatic physiological effects on animals that are associated with improved survival. C. elegans grown in H2S are long-lived and thermotolerant. To identify mechanisms by which adaptation to H2S effects physiological functions, we have measured transcriptional responses to H2S exposure. Using microarray analysis we observe rapid changes in the abundance of specific mRNAs. The number and magnitude of transcriptional changes increased with the duration of H2S exposure. Functional annotation suggests that genes associated with protein homeostasis are upregulated upon prolonged exposure to H2S. Previous work has shown that the hypoxia-inducible transcription factor, HIF 1, is required for survival in H2S. In fact, we show that hif-1 is required for most, if not all, early transcriptional changes in H2S. Moreover, our data demonstrate that SKN-1, the C. elegans homologue of NRF2, also contributes to H2S dependent changes in transcription. We show that these results are functionally important, as skn-1 is essential to survive exposure to H2S. Our results suggest a model in which HIF-1 and SKN-1 coordinate a broad transcriptional response to H2S that culminates in a global reorganization of protein homeostasis networks. PMID- 21980474 TI - Deletion of a malaria invasion gene reduces death and anemia, in model hosts. AB - Malaria parasites induce complex cellular and clinical phenotypes, including anemia, cerebral malaria and death in a wide range of mammalian hosts. Host genes and parasite 'toxins' have been implicated in malarial disease, but the contribution of parasite genes remains to be fully defined. Here we assess disease in BALB/c mice and Wistar rats infected by the rodent malaria parasite Plasmodium berghei with a gene knock out for merozoite surface protein (MSP) 7. MSP7 is not essential for infection but in P. falciparum, it enhances erythrocyte invasion by 20%. In vivo, as compared to wild type, the P. berghei Deltamsp7 mutant is associated with an abrogation of death and a decrease from 3% to 2% in peak, circulating parasitemia. The Deltamsp7 mutant is also associated with less anemia and modest increase in the size of follicles in the spleen. Together these data show that deletion of a single parasite invasion ligand modulates blood stage disease, as measured by death and anemia. This work is the first to assess the contribution of a gene present in all plasmodial species in severe disease. PMID- 21980475 TI - Impact of CD1d deficiency on metabolism. AB - Invariant natural killer T cells (iNKTs) are innate-like T cells that are highly concentrated in the liver and recognize lipids presented on the MHC-like molecule CD1d. Although capable of a myriad of responses, few essential functions have been described for iNKTs. Among the many cell types of the immune system implicated in metabolic control and disease, iNKTs seem ideally poised for such a role, yet little has been done to elucidate such a possible function. We hypothesized that lipid presentation by CD1d could report on metabolic status and engage iNKTs to regulate cellular lipid content through their various effector mechanisms. To test this hypothesis, we examined CD1d deficient mice in a variety of metabolically stressed paradigms including high fat feeding, choline-deficient feeding, fasting, and acute inflammation. CD1d deficiency led to a mild exacerbation of steatosis during high fat or choline-deficient feeding, accompanied by impaired hepatic glucose tolerance. Surprisingly, however, this phenotype was not observed in Jalpha18-/- mice, which are deficient in iNKTs but express CD1d. Thus, CD1d appears to modulate some metabolic functions through an iNKT-independent mechanism. PMID- 21980476 TI - Downregulation of the Hsp90 system causes defects in muscle cells of Caenorhabditis elegans. AB - The ATP-dependent molecular chaperone Hsp90 is required for the activation of a variety of client proteins involved in various cellular processes. Despite the abundance of known client proteins, functions of Hsp90 in the organismal context are not fully explored. In Caenorhabditis elegans, Hsp90 (DAF-21) has been implicated in the regulation of the stress-resistant dauer state, in chemosensing and in gonad formation. In a C. elegans strain carrying a DAF-21 mutation with a lower ATP turnover, we observed motility defects. Similarly, a reduction of DAF 21 levels in wild type nematodes leads to reduced motility and induction of the muscular stress response. Furthermore, aggregates of the myosin MYO-3 are visible in muscle cells, if DAF-21 is depleted, implying a role of Hsp90 in the maintenance of muscle cell functionality. Similar defects can also be observed upon knockdown of the Hsp90-cochaperone UNC-45. In life nematodes YFP-DAF-21 localizes to the I-band and the M-line of the muscular ultrastructure, but the protein is not stably attached there. The Hsp90-cofactor UNC-45-CFP contrarily can be found in all bands of the nematode muscle ultrastructure and stably associates with the UNC-54 containing A-band. Thus, despite the physical interaction between DAF-21 and UNC-45, apparently the two proteins are not always localized to the same muscular structures. While UNC-45 can stably bind to myofilaments in the muscular ultrastructure, Hsp90 (DAF-21) appears to participate in the maintenance of muscle structures as a transiently associated diffusible factor. PMID- 21980477 TI - Bacteriophage-resistant mutants in Yersinia pestis: identification of phage receptors and attenuation for mice. AB - BACKGROUND: Bacteriophages specific for Yersinia pestis are routinely used for plague diagnostics and could be an alternative to antibiotics in case of drug resistant plague. A major concern of bacteriophage therapy is the emergence of phage-resistant mutants. The use of phage cocktails can overcome this problem but only if the phages exploit different receptors. Some phage-resistant mutants lose virulence and therefore should not complicate bacteriophage therapy. METHODOLOGY/PRINCIPAL FINDINGS: The purpose of this work was to identify Y. pestis phage receptors using site-directed mutagenesis and trans-complementation and to determine potential attenuation of phage-resistant mutants for mice. Six receptors for eight phages were found in different parts of the lipopolysaccharide (LPS) inner and outer core. The receptor for R phage was localized beyond the LPS core. Most spontaneous and defined phage-resistant mutants of Y. pestis were attenuated, showing increase in LD50 and time to death. The loss of different LPS core biosynthesis enzymes resulted in the reduction of Y. pestis virulence and there was a correlation between the degree of core truncation and the impact on virulence. The yrbH and waaA mutants completely lost their virulence. CONCLUSIONS/SIGNIFICANCE: We identified Y. pestis receptors for eight bacteriophages. Nine phages together use at least seven different Y. pestis receptors that makes some of them promising for formulation of plague therapeutic cocktails. Most phage-resistant Y. pestis mutants become attenuated and thus should not pose a serious problem for bacteriophage therapy of plague. LPS is a critical virulence factor of Y. pestis. PMID- 21980478 TI - Immunoprotectivity of HLA-A2 CTL peptides derived from respiratory syncytial virus fusion protein in HLA-A2 transgenic mouse. AB - Identification of HLA-restricted CD8+ T cell epitopes is important to study RSV induced immunity and illness. We algorithmically analyzed the sequence of the fusion protein (F) of respiratory syncytial virus (RSV) and generated synthetic peptides that can potentially bind to HLA-A*0201. Four out of the twenty-five 9 mer peptides tested: peptides 3 (F33-41), 13 (F214-222), 14 (F273-281), and 23 (F559-567), were found to bind to HLA-A*0201 with moderate to high affinity and were capable of inducing IFN-gamma and IL-2 secretion in lymphocytes from HLA A*0201 transgenic (HLA-Tg) mice pre-immunized with RSV or recombinant adenovirus expressing RSV F. HLA-Tg mice were immunized with these four peptides and were found to induce both Th1 and CD8+ T cell responses in in vitro secondary recall. Effector responses induced by these peptides were observed to confer differential protection against live RSV challenge. These peptides also caused better recovery of body weight loss induced by RSV. A significant reduction of lung viral load was observed in mice immunized with peptide 23, which appeared to enhance the levels of inflammatory chemokines (CCL17, CCL22, and IL-18) but did not increase eosinophil infiltration in the lungs. Whereas, significant reduction of infiltrated eosinophils induced by RSV infection was found in mice pre-immunized with peptide 13. Our results suggest that HLA-A2-restricted epitopes of RSV F protein could be useful for the development of epitope-based RSV vaccine. PMID- 21980479 TI - Reprogramming of Escherichia coli K-12 metabolism during the initial phase of transition from an anaerobic to a micro-aerobic environment. AB - BACKGROUND: Many bacteria undergo transitions between environments with differing O2 availabilities as part of their natural lifestyles and during biotechnological processes. However, the dynamics of adaptation when bacteria experience changes in O2 availability are understudied. The model bacterium and facultative anaerobe Escherichia coli K-12 provides an ideal system for exploring this process. METHODS AND FINDINGS: Time-resolved transcript profiles of E. coli K-12 during the initial phase of transition from anaerobic to micro-aerobic conditions revealed a reprogramming of gene expression consistent with a switch from fermentative to respiratory metabolism. The changes in transcript abundance were matched by changes in the abundances of selected central metabolic proteins. A probabilistic state space model was used to infer the activities of two key regulators, FNR (O2 sensing) and PdhR (pyruvate sensing). The model implied that both regulators were rapidly inactivated during the transition from an anaerobic to a micro-aerobic environment. Analysis of the external metabolome and protein levels suggested that the cultures transit through different physiological states during the process of adaptation, characterized by the rapid inactivation of pyruvate formate-lyase (PFL), a slower induction of pyruvate dehydrogenase complex (PDHC) activity and transient excretion of pyruvate, consistent with the predicted inactivation of PdhR and FNR. CONCLUSION: Perturbation of anaerobic steady-state cultures by introduction of a limited supply of O2 combined with time-resolved transcript, protein and metabolite profiling, and probabilistic modeling has revealed that pyruvate (sensed by PdhR) is a key metabolic signal in coordinating the reprogramming of E. coli K-12 gene expression by working alongside the O2 sensor FNR during transition from anaerobic to micro-aerobic conditions. PMID- 21980480 TI - Auditory-motor mapping training as an intervention to facilitate speech output in non-verbal children with autism: a proof of concept study. AB - Although up to 25% of children with autism are non-verbal, there are very few interventions that can reliably produce significant improvements in speech output. Recently, a novel intervention called Auditory-Motor Mapping Training (AMMT) has been developed, which aims to promote speech production directly by training the association between sounds and articulatory actions using intonation and bimanual motor activities. AMMT capitalizes on the inherent musical strengths of children with autism, and offers activities that they intrinsically enjoy. It also engages and potentially stimulates a network of brain regions that may be dysfunctional in autism. Here, we report an initial efficacy study to provide 'proof of concept' for AMMT. Six non-verbal children with autism participated. Prior to treatment, the children had no intelligible words. They each received 40 individual sessions of AMMT 5 times per week, over an 8-week period. Probe assessments were conducted periodically during baseline, therapy, and follow-up sessions. After therapy, all children showed significant improvements in their ability to articulate words and phrases, with generalization to items that were not practiced during therapy sessions. Because these children had no or minimal vocal output prior to treatment, the acquisition of speech sounds and word approximations through AMMT represents a critical step in expressive language development in children with autism. PMID- 21980481 TI - Kv7 channels can function without constitutive calmodulin tethering. AB - M-channels are voltage-gated potassium channels composed of Kv7.2-7.5 subunits that serve as important regulators of neuronal excitability. Calmodulin binding is required for Kv7 channel function and mutations in Kv7.2 that disrupt calmodulin binding cause Benign Familial Neonatal Convulsions (BFNC), a dominantly inherited human epilepsy. On the basis that Kv7.2 mutants deficient in calmodulin binding are not functional, calmodulin has been defined as an auxiliary subunit of Kv7 channels. However, we have identified a presumably phosphomimetic mutation S511D that permits calmodulin-independent function. Thus, our data reveal that constitutive tethering of calmodulin is not required for Kv7 channel function. PMID- 21980482 TI - Aggravation of chronic stress effects on hippocampal neurogenesis and spatial memory in LPA1 receptor knockout mice. AB - BACKGROUND: The lysophosphatidic acid LPA1 receptor regulates plasticity and neurogenesis in the adult hippocampus. Here, we studied whether absence of the LPA1 receptor modulated the detrimental effects of chronic stress on hippocampal neurogenesis and spatial memory. METHODOLOGY/PRINCIPAL FINDINGS: Male LPA1-null (NULL) and wild-type (WT) mice were assigned to control or chronic stress conditions (21 days of restraint, 3 h/day). Immunohistochemistry for bromodeoxyuridine and endogenous markers was performed to examine hippocampal cell proliferation, survival, number and maturation of young neurons, hippocampal structure and apoptosis in the hippocampus. Corticosterone levels were measured in another a separate cohort of mice. Finally, the hole-board test assessed spatial reference and working memory. Under control conditions, NULL mice showed reduced cell proliferation, a defective population of young neurons, reduced hippocampal volume and moderate spatial memory deficits. However, the primary result is that chronic stress impaired hippocampal neurogenesis in NULLs more severely than in WT mice in terms of cell proliferation; apoptosis; the number and maturation of young neurons; and both the volume and neuronal density in the granular zone. Only stressed NULLs presented hypocortisolemia. Moreover, a dramatic deficit in spatial reference memory consolidation was observed in chronically stressed NULL mice, which was in contrast to the minor effect observed in stressed WT mice. CONCLUSIONS/SIGNIFICANCE: These results reveal that the absence of the LPA1 receptor aggravates the chronic stress-induced impairment to hippocampal neurogenesis and its dependent functions. Thus, modulation of the LPA1 receptor pathway may be of interest with respect to the treatment of stress induced hippocampal pathology. PMID- 21980483 TI - Novel nucleotide and amino acid covariation between the 5'UTR and the NS2/NS3 proteins of hepatitis C virus: bioinformatic and functional analyses. AB - Molecular covariation of highly polymorphic viruses is thought to have crucial effects on viral replication and fitness. This study employs association rule data mining of hepatitis C virus (HCV) sequences to search for specific evolutionary covariation and then tests functional relevance on HCV replication. Data mining is performed between nucleotides in the untranslated regions 5' and 3'UTR, and the amino acid residues in the non-structural proteins NS2, NS3 and NS5B. Results indicate covariance of the 243(rd) nucleotide of the 5'UTR with the 14(th), 41(st), 76(th), 110(th), 211(th) and 212(th) residues of NS2 and with the 71(st), 175(th) and 621(st) residues of NS3. Real-time experiments using an HCV subgenomic system to quantify viral replication confirm replication regulation for each covariant pair between 5'UTR243 and NS2-41, -76, -110, -211, and NS3-71, -175. The HCV subgenomic system with/without the NS2 region shows that regulatory effects vanish without NS2, so replicative modulation mediated by HCV 5'UTR243 depends on NS2. Strong binding of the NS2 variants to HCV RNA correlates with reduced HCV replication whereas weak binding correlates with restoration of HCV replication efficiency, as determined by RNA-protein immunoprecipitation assay band intensity. The dominant haplotype 5'UTR243-NS2-41-76-110-211-NS3-71-175 differs according to the HCV genotype: G-Ile-Ile-Ile-Gly-Ile-Met for genotype 1b and A-Leu-Val-Leu-Ser-Val-Leu for genotypes 1a, 2a and 2b. In conclusion, 5'UTR243 co-varies with specific NS2/3 protein amino acid residues, which may have significant structural and functional consequences for HCV replication. This unreported mechanism involving HCV replication possibly can be exploited in the development of advanced anti-HCV medication. PMID- 21980484 TI - Practical tools to implement massive parallel pyrosequencing of PCR products in next generation molecular diagnostics. AB - Despite improvements in terms of sequence quality and price per basepair, Sanger sequencing remains restricted to screening of individual disease genes. The development of massively parallel sequencing (MPS) technologies heralded an era in which molecular diagnostics for multigenic disorders becomes reality. Here, we outline different PCR amplification based strategies for the screening of a multitude of genes in a patient cohort. We performed a thorough evaluation in terms of set-up, coverage and sequencing variants on the data of 10 GS-FLX experiments (over 200 patients). Crucially, we determined the actual coverage that is required for reliable diagnostic results using MPS, and provide a tool to calculate the number of patients that can be screened in a single run. Finally, we provide an overview of factors contributing to false negative or false positive mutation calls and suggest ways to maximize sensitivity and specificity, both important in a routine setting. By describing practical strategies for screening of multigenic disorders in a multitude of samples and providing answers to questions about minimum required coverage, the number of patients that can be screened in a single run and the factors that may affect sensitivity and specificity we hope to facilitate the implementation of MPS technology in molecular diagnostics. PMID- 21980485 TI - Cerebral blood flow during rest associates with general intelligence and creativity. AB - Recently, much scientific attention has been focused on resting brain activity and its investigation through such methods as the analysis of functional connectivity during rest (the temporal correlation of brain activities in different regions). However, investigation of the magnitude of brain activity during rest has focused on the relative decrease of brain activity during a task, rather than on the absolute resting brain activity. It is thus necessary to investigate the association between cognitive factors and measures of absolute resting brain activity, such as cerebral blood flow (CBF), during rest (rest CBF). In this study, we examined this association using multiple regression analyses. Rest-CBF was the dependent variable and the independent variables included two essential components of cognitive functions, psychometric general intelligence and creativity. CBF was measured using arterial spin labeling and there were three analyses for rest-CBF; namely mean gray matter rest-CBF, mean white matter rest-CBF, and regional rest-CBF. The results showed that mean gray and white matter rest-CBF were significantly and positively correlated with individual psychometric intelligence. Furthermore, mean white matter rest-CBF was significantly and positively correlated with creativity. After correcting the effect of mean gray matter rest-CBF the significant and positive correlation between regional rest-CBF in the perisylvian anatomical cluster that includes the left superior temporal gyrus and insula and individual psychometric intelligence was found. Also, regional rest-CBF in the precuneus was significantly and negatively correlated with individual creativity. Significance of these results of regional rest-CBF did not change when the effect of regional gray matter density was corrected. The findings showed mean and regional rest-CBF in healthy young subjects to be correlated with cognitive functions. The findings also suggest that, even in young cognitively intact subjects, resting brain activity (possibly underlain by default cognitive activity or metabolic demand from developed brain structures) is associated with cognitive functions. PMID- 21980486 TI - Early-life determinants of total and HDL cholesterol concentrations in 8-year-old children; the PIAMA birth cohort study. AB - BACKGROUND: Adult cholesterol concentrations might be influenced by early-life factors, such as breastfeeding and birth weight, referred to as "early programming". How such early factors exert their influence over the life course is still poorly understood. Evidence from studies in children and adolescents is scarce and conflicting. We investigated the influence of 6 different perinatal risk factors on childhood total and HDL cholesterol concentrations and total-to HDL cholesterol ratio measured at 8 years of age, and additionally we studied the role of the child's current Body Mass Index (BMI). METHODS: Anthropometric measures and blood plasma samples were collected during a medical examination in 751 8-year-old children participating in the prospective Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study. Linear and logistic regression were performed to estimate associations of total and HDL cholesterol concentrations with breastfeeding, birth weight, infant weight gain, maternal overweight before pregnancy, gestational diabetes and maternal smoking during pregnancy, taking into account the child's current BMI. RESULTS: Linear regressions showed an association between total-to-HDL cholesterol ratio and maternal pre-pregnancy overweight (beta = 0.15, Confidence Interval 95% (CI): 0.02, 0.28), rapid infant weight gain (beta = 0.13, 95%CI: 0.01, 0.26), and maternal smoking during pregnancy (beta = 0.14, 95%CI: 0.00, 0.29). These associations were partly mediated by the child's BMI. CONCLUSION: Total-to-HDL cholesterol ratio in 8-year-old children was positively associated with maternal pre-pregnancy overweight, maternal smoking during pregnancy and rapid infant weight gain. PMID- 21980487 TI - Measurements of elastic moduli of silicone gel substrates with a microfluidic device. AB - Thin layers of gels with mechanical properties mimicking animal tissues are widely used to study the rigidity sensing of adherent animal cells and to measure forces applied by cells to their substrate with traction force microscopy. The gels are usually based on polyacrylamide and their elastic modulus is measured with an atomic force microscope (AFM). Here we present a simple microfluidic device that generates high shear stresses in a laminar flow above a gel-coated substrate and apply the device to gels with elastic moduli in a range from 0.4 to 300 kPa that are all prepared by mixing two components of a transparent commercial silicone Sylgard 184. The elastic modulus is measured by tracking beads on the gel surface under a wide-field fluorescence microscope without any other specialized equipment. The measurements have small and simple to estimate errors and their results are confirmed by conventional tensile tests. A master curve is obtained relating the mixing ratios of the two components of Sylgard 184 with the resulting elastic moduli of the gels. The rigidity of the silicone gels is less susceptible to effects from drying, swelling, and aging than polyacrylamide gels and can be easily coated with fluorescent tracer particles and with molecules promoting cellular adhesion. This work can lead to broader use of silicone gels in the cell biology laboratory and to improved repeatability and accuracy of cell traction force microscopy and rigidity sensing experiments. PMID- 21980488 TI - Requirement of interaction between mast cells and skin dendritic cells to establish contact hypersensitivity. AB - The role of mast cells (MCs) in contact hypersensitivity (CHS) remains controversial. This is due in part to the use of the MC-deficient Kit (W/Wv) mouse model, since Kit (W/Wv) mice congenitally lack other types of cells as a result of a point mutation in c-kit. A recent study indicated that the intronic enhancer (IE) for Il4 gene transcription is essential for MCs but not in other cell types. The aim of this study is to re-evaluate the roles of MCs in CHS using mice in which MCs can be conditionally and specifically depleted. Transgenic Mas TRECK mice in which MCs are depleted conditionally were newly generated using cell-type specific gene regulation by IE. Using this mouse, CHS and FITC-induced cutaneous DC migration were analyzed. Chemotaxis assay and cytoplasmic Ca2+ imaging were performed by co-culture of bone marrow-derived MCs (BMMCs) and bone marrow-derived dendritic cells (BMDCs). In Mas-TRECK mice, CHS was attenuated when MCs were depleted during the sensitization phase. In addition, both maturation and migration of skin DCs were abrogated by MC depletion. Consistently, BMMCs enhanced maturation and chemotaxis of BMDC in ICAM-1 and TNF alpha dependent manners Furthermore, stimulated BMDCs increased intracellular Ca2+ of MC upon direct interaction and up-regulated membrane-bound TNF-alpha on BMMCs. These results suggest that MCs enhance DC functions by interacting with DCs in the skin to establish the sensitization phase of CHS. PMID- 21980489 TI - TTRAP is a novel component of the non-canonical TRAF6-TAK1 TGF-beta signaling pathway. AB - Transforming growth factor-beta (TGF-beta) principally relays its effects through the Smad pathway however, accumulating evidence indicate that alternative signaling routes are also employed by this pleiotropic cytokine. For instance recently, we have demonstrated that ligand occupied TGF-beta receptors can directly trigger the TRAF6-TAK1 signaling module, resulting in MAP kinase activation. Here we report identification of the adaptor molecule TTRAP as a novel component of this non-canonical TGF-beta pathway. We show that the protein associates with TGF-beta receptors and components of the TRAF6-TAK1 signaling module, resulting in differential regulation of TGF-beta activated p38 and NF kappaB responses. Modulation of cellular TTRAP level affects cell viability in the presence of TGF-beta, suggesting that the protein is an important component of the TGF-beta induced apoptotic process. PMID- 21980490 TI - Phylogenetic inconsistency caused by ancient sex-biased gene migration. AB - Inferences of ancient sex-biased migration patterns using sex-linked genetic markers are usually difficult because of a stochastic process of allele fixation. Nevertheless, incongruent phylogenetic trees between different sex-linked markers and between sex-linked and autosomal markers are frequently interpreted as a signature of sex-biased migration without further statistical evaluation. I investigated the types of incongruent phylogenetic trees from which past sex biased migration events can be statistically supported under the coalescent model. In the case of mammals, detecting a sex-biased migration pattern is not guaranteed by comparing the phylogenetic pattern of mitochondrial and Y chromosomal loci. Likewise, evidence of introgression at a mitochondrial locus, but not at autosomal loci, does not support the hypothesis of an ancient female biased migration pattern with statistical significance. In contrast, evidence of introgression at >= 5 unlinked autosomal loci, but not at a Y-chromosomal locus, would reject the null hypothesis of a sexually equal migration rate with statistical significance. A similar argument can be made to infer a male-biased migration pattern. Furthermore, the investigation of many recombining sex-biased markers such as X-chromosomal loci in mammals has the potential to efficiently detect ancient sex-biased demographic patterns. PMID- 21980492 TI - Increasing oxygen radicals and water temperature select for toxic Microcystis sp. AB - Pronounced rises in frequency of toxic cyanobacterial blooms are recently observed worldwide, particularly when temperatures increase. Different strains of cyanobacterial species vary in their potential to produce toxins but driving forces are still obscure. Our study examines effects of hydrogen peroxide on toxic and non-toxic (including a non-toxic mutant) strains of M. aeruginosa. Here we show that hydrogen peroxide diminishes chlorophyll a content and growth of cyanobacteria and that this reduction is significantly lower for toxic than for non-toxic strains. This indicates that microcystins protect from detrimental effects of oxygen radicals. Incubation of toxic and non-toxic strains of M. aeruginosa with other bacteria or without (axenic) at three temperatures (20, 26 and 32 degrees C) reveals a shift toward toxic strains at higher temperatures. In parallel to increases in abundance of toxic (i.e. toxin gene possessing) strains and their actual toxin expression, concentrations of microcystins rise with temperature, when amounts of radicals are expected to be enhanced. Field samples from three continents support the influence of radicals and temperature on toxic potential of M. aeruginosa. Our results imply that global warming will significantly increase toxic potential and toxicity of cyanobacterial blooms which has strong implications for socio-economical assessments of global change. PMID- 21980491 TI - Mechanisms of the anti-obesity effects of oxytocin in diet-induced obese rats. AB - Apart from its role during labor and lactation, oxytocin is involved in several other functions. Interestingly, oxytocin- and oxytocin receptor-deficient mice develop late-onset obesity with normal food intake, suggesting that the hormone might exert a series of beneficial metabolic effects. This was recently confirmed by data showing that central oxytocin infusion causes weight loss in diet-induced obese mice. The aim of the present study was to unravel the mechanisms underlying such beneficial effects of oxytocin. Chronic central oxytocin infusion was carried out in high fat diet-induced obese rats. Its impact on body weight, lipid metabolism and insulin sensitivity was determined. We observed a dose-dependent decrease in body weight gain, increased adipose tissue lipolysis and fatty acid beta-oxidation, as well as reduced glucose intolerance and insulin resistance. The additional observation that plasma oxytocin levels increased upon central infusion suggested that the hormone might affect adipose tissue metabolism by direct action. This was demonstrated using in vitro, ex vivo, as well as in vivo experiments. With regard to its mechanism of action in adipose tissue, oxytocin increased the expression of stearoyl-coenzyme A desaturase 1, as well as the tissue content of the phospholipid precursor, N-oleoyl-phosphatidylethanolamine, the biosynthetic precursor of the oleic acid-derived PPAR-alpha activator, oleoylethanolamide. Because PPAR-alpha regulates fatty acid beta-oxidation, we hypothesized that this transcription factor might mediate the oxytocin effects. This was substantiated by the observation that, in contrast to its effects in wild-type mice, oxytocin infusion failed to induce weight loss and fat oxidation in PPAR-alpha-deficient animals. Altogether, these results suggest that oxytocin administration could represent a promising therapeutic approach for the treatment of human obesity and type 2 diabetes. PMID- 21980493 TI - Human cysteine cathepsins are not reliable markers of infection by Pseudomonas aeruginosa in cystic fibrosis. AB - Cysteine cathepsins have emerged as new players in inflammatory lung disorders. Their activities are dramatically increased in the sputum of cystic fibrosis (CF) patients, suggesting that they are involved in the pathophysiology of CF. We have characterized the cathepsins in CF expectorations and evaluated their use as markers of colonization by Pseudomonas aeruginosa. The concentrations of active cathepsins B, H, K, L and S were the same in P. aeruginosa-positive (19 Ps+) and P. aeruginosa-negative (6 Ps-) samples, unlike those of human neutrophil elastase. Also the cathepsin inhibitory potential and the cathepsins/cathepsin inhibitors imbalance remained unchanged and similar (~2-fold) in the Ps+ and Ps- groups (p<0.001), which correlated with the breakdown of their circulating cystatin-like inhibitors (kininogens). Procathepsins, which may be activated autocatalytically, are a potential proteolytic reservoir. Immunoblotting and active-site labeling identified the double-chain cathepsin B, the major cathepsin in CF sputum, as the main molecular form in both Ps+ and Ps- samples, despite the possible release of the ~31 kDa single-chain form from procathepsin B by sputum elastase. Thus, the hydrolytic activity of cysteine cathepsins was not correlated with bacterial colonization, indicating that cathepsins, unlike human neutrophil elastase, are not suitable markers of P. aeruginosa infection. PMID- 21980494 TI - Genetics of venous thrombosis: insights from a new genome wide association study. AB - BACKGROUND: Venous Thrombosis (VT) is a common multifactorial disease associated with a major public health burden. Genetics factors are known to contribute to the susceptibility of the disease but how many genes are involved and their contribution to VT risk still remain obscure. We aimed to identify genetic variants associated with VT risk. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a genome-wide association study (GWAS) based on 551,141 SNPs genotyped in 1,542 cases and 1,110 controls. Twelve SNPs reached the genome-wide significance level of 2.0*10(-8) and encompassed four known VT-associated loci, ABO, F5, F11 and FGG. By means of haplotype analyses, we also provided novel arguments in favor of a role of HIVEP1, PROCR and STAB2, three loci recently hypothesized to participate in the susceptibility to VT. However, no novel VT-associated loci came out of our GWAS. Using a recently proposed statistical methodology, we also showed that common variants could explain about 35% of the genetic variance underlying VT susceptibility among which 3% could be attributable to the main identified VT loci. This analysis additionally suggested that the common variants left to be identified are not uniformly distributed across the genome and that chromosome 20, itself, could contribute to ~7% of the total genetic variance. CONCLUSIONS/SIGNIFICANCE: This study might also provide a valuable source of information to expand our understanding of biological mechanisms regulating quantitative biomarkers for VT. PMID- 21980495 TI - ProteinSeq: high-performance proteomic analyses by proximity ligation and next generation sequencing. AB - Despite intense interest, methods that provide enhanced sensitivity and specificity in parallel measurements of candidate protein biomarkers in numerous samples have been lacking. We present herein a multiplex proximity ligation assay with readout via realtime PCR or DNA sequencing (ProteinSeq). We demonstrate improved sensitivity over conventional sandwich assays for simultaneous analysis of sets of 35 proteins in 5 ul of blood plasma. Importantly, we observe a minimal tendency to increased background with multiplexing, compared to a sandwich assay, suggesting that higher levels of multiplexing are possible. We used ProteinSeq to analyze proteins in plasma samples from cardiovascular disease (CVD) patient cohorts and matched controls. Three proteins, namely P-selectin, Cystatin-B and Kallikrein-6, were identified as putative diagnostic biomarkers for CVD. The latter two have not been previously reported in the literature and their potential roles must be validated in larger patient cohorts. We conclude that ProteinSeq is promising for screening large numbers of proteins and samples while the technology can provide a much-needed platform for validation of diagnostic markers in biobank samples and in clinical use. PMID- 21980496 TI - Tumor necrosis factor alpha-converting enzyme inhibition reverses hepatic steatosis and improves insulin sensitivity markers and surgical outcome in mice. AB - BACKGROUND: Hepatic steatosis is an established risk factor for complications following major hepatic resection. Pharmacological options to reverse steatosis prior to surgery, however, are lacking. We hypothesized that treatment with the pharmacologic tumor necrosis factor-alpha converting enzyme (TACE)-inhibitor Marimastat would reverse established steatosis, leading to improved outcome following hepatectomy. METHODOLOGY/PRINCIPAL FINDINGS: C57BL/6 male mice were fed a high fat diet for 9 weeks to establish obesity, hepatic steatosis and insulin resistance, and were administered either Marimastat or vehicle for an additional 2 or 4 weeks. Leptin deficient, hyperinsulinemic ob/ob mice were treated with Marimastat for 4 weeks. Hepatic steatosis was quantified by magnetic resonance spectroscopy and confirmed by histology. After two weeks, Marimastat-treated animals significantly improved surrogate markers for insulin sensitivity and liver histology, and experienced a 66% decrease in steatosis (P = 0.010). These findings were confirmed in ob/ob mice. Transcripts related to fatty acid synthesis were significantly downregulated in Marimastat-treated animals. Following pre-treatment with Marimastat or vehicle for two weeks, high fat fed C57BL/6 mice were subjected to two-thirds hepatectomy. Post-operative liver injury as quantified by serum aspartate aminotransferase levels and alanine aminotransferase levels was significantly decreased by 57% (P = 0.020) and 44% (P = 0.032) respectively, compared to controls. CONCLUSION/SIGNIFICANCE: Treatment with the TACE-inhibitor Marimastat improved surrogate markers for insulin sensitivity and reversed steatosis in mouse models of diet-induced obesity and leptin deficiency, thereby attenuating post-operative injury following hepatectomy. This may suggest a potential therapeutic role in patients with fatty liver disease; especially those who need to undergo hepatic resection. PMID- 21980497 TI - Big defensins, a diverse family of antimicrobial peptides that follows different patterns of expression in hemocytes of the oyster Crassostrea gigas. AB - BACKGROUND: Big defensin is an antimicrobial peptide composed of a highly hydrophobic N-terminal region and a cationic C-terminal region containing six cysteine residues involved in three internal disulfide bridges. While big defensin sequences have been reported in various mollusk species, few studies have been devoted to their sequence diversity, gene organization and their expression in response to microbial infections. FINDINGS: Using the high throughput Digital Gene Expression approach, we have identified in Crassostrea gigas oysters several sequences coding for big defensins induced in response to a Vibrio infection. We showed that the oyster big defensin family is composed of three members (named Cg-BigDef1, Cg-BigDef2 and Cg-BigDef3) that are encoded by distinct genomic sequences. All Cg-BigDefs contain a hydrophobic N-terminal domain and a cationic C-terminal domain that resembles vertebrate beta-defensins. Both domains are encoded by separate exons. We found that big defensins form a group predominantly present in mollusks and closer to vertebrate defensins than to invertebrate and fungi CSalphabeta-containing defensins. Moreover, we showed that Cg-BigDefs are expressed in oyster hemocytes only and follow different patterns of gene expression. While Cg-BigDef3 is non-regulated, both Cg-BigDef1 and Cg-BigDef2 transcripts are strongly induced in response to bacterial challenge. Induction was dependent on pathogen associated molecular patterns but not damage-dependent. The inducibility of Cg-BigDef1 was confirmed by HPLC and mass spectrometry, since ions with a molecular mass compatible with mature Cg BigDef1 (10.7 kDa) were present in immune-challenged oysters only. From our biochemical data, native Cg-BigDef1 would result from the elimination of a prepropeptide sequence and the cyclization of the resulting N-terminal glutamine residue into a pyroglutamic acid. CONCLUSIONS: We provide here the first report showing that big defensins form a family of antimicrobial peptides diverse not only in terms of sequences but also in terms of genomic organization and regulation of gene expression. PMID- 21980498 TI - Mesodermal progenitor cells (MPCs) differentiate into mesenchymal stromal cells (MSCs) by activation of Wnt5/calmodulin signalling pathway. AB - BACKGROUND: Mesenchymal Stromal Cells (MSCs) remain poorly characterized because of the absence of manifest physical, phenotypic, and functional properties in cultured cell populations. Despite considerable research on MSCs and their clinical application, the biology of these cells is not fully clarified and data on signalling activation during mesenchymal differentiation and proliferation are controversial. The role of Wnt pathways is still debated, partly due to culture heterogeneity and methodological inconsistencies. Recently, we described a new bone marrow cell population isolated from MSC cultures that we named Mesodermal Progenitor Cells (MPCs) for their mesenchymal and endothelial differentiation potential. An optimized culture method allowed the isolation from human adult bone marrow of a highly pure population of MPCs (more than 97%), that showed the distinctive SSEA-4+CD105+CD90(neg) phenotype and not expressing MSCA-1 antigen. Under these selective culture conditions the percentage of MSCs (SSEA 4(neg)CD105+CD90(bright) and MSCA-1+), in the primary cultures, resulted lower than 2%. METHODOLOGY/PRINCIPAL FINDING: We demonstrate that MPCs differentiate to MSCs through an SSEA-4+CD105+CD90(bright) early intermediate precursor. Differentiation paralleled the activation of Wnt5/Calmodulin signalling by autocrine/paracrine intense secretion of Wnt5a and Wnt5b (p<0.05 vs uncondictioned media), which was later silenced in late MSCs (SSEA-4(neg)). We found the inhibition of this pathway by calmidazolium chloride specifically blocked mesenchymal induction (ID50 = 0.5 uM, p<0.01), while endothelial differentiation was unaffected. CONCLUSION: The present study describes two different putative progenitors (early and late MSCs) that, together with already described MPCs, could be co-isolated and expanded in different percentages depending on the culture conditions. These results suggest that some modifications to the widely accepted MSC nomenclature are required. PMID- 21980499 TI - An integrated meta-analysis of two variants in HOXA1/HOXB1 and their effect on the risk of autism spectrum disorders. AB - BACKGROUND: HOXA1 and HOXB1 have been strongly posed as candidate genes for autism spectrum disorders (ASD) given their important role in the development of hindbrain. The A218G (rs10951154) in HOXA1 and the insertion variant in HOXB1 (nINS/INS, rs72338773) were of special interest for ASD but with inconclusive results. Thus, we conducted a meta-analysis integrating case-control and transmission/disequilibrium test (TDT) studies to clearly discern the effect of these two variants in ASD. METHODS AND FINDINGS: Multiple electronic databases were searched to identify studies assessing the A218G and/or nINS/INS variant in ASD. Data from case-control and TDT studies were analyzed in an allelic model using the Catmap software. A total of 10 and 7 reports were found to be eligible for meta-analyses of A218G and nINS/INS variant, respectively. In overall meta analysis, the pooled OR for the 218G allele and the INS allele was 0.97 (95% CI = 0.76-1.25, P(heterogeneity) = 0.029) and 1.14 (95% CI = 0.97-1.33, P(heterogeneity) = 0.269), respectively. No significant association was also identified between these two variants and ASD risk in stratified analysis. Further, cumulative meta-analysis in chronologic order showed the inclination toward null-significant association for both variants with continual adding studies. Additionally, although the between-study heterogeneity regarding the A218G is not explained by study design, ethnicity, and sample size, the sensitive analysis indicated the stability of the result. CONCLUSIONS: This meta-analysis suggests the HOXA1 A218G and HOXB1 nINS/INS variants may not contribute significantly to ASD risk. PMID- 21980500 TI - Antibody V(h) repertoire differences between resolving and chronically evolving hepatitis C virus infections. AB - Despite the production of neutralizing antibodies to hepatitis C virus (HCV), many patients fail to clear the virus and instead develop chronic infection and long-term complications. To understand how HCV infection perturbs the antibody repertoire and to identify molecular features of antibody genes associated with either viral clearance or chronic infection, we sequenced the V(D)J region of naive and memory B cells of 6 persons who spontaneously resolved an HCV infection (SR), 9 patients with a newly diagnosed chronically evolving infection (CE), and 7 healthy donors. In both naive and memory B cells, the frequency of use of particular antibody gene subfamilies and segments varied among the three clinical groups, especially between SR and CE. Compared to CE, SR antibody genes used fewer VH, D and JH gene segments in naive B cells and fewer VH segments in memory B cells. SR and CE groups significantly differed in the frequency of use of 7 gene segments in naive B cell clones and 3 gene segments in memory clones. The nucleotide mutation rates were similar among groups, but the pattern of replacement and silent mutations in memory B cell clones indicated greater antigen selection in SR than CE. Greater clonal evolution of SR than CE memory B cells was revealed by analysis of phylogenetic trees and CDR3 lengths. Pauciclonality of the peripheral memory B cell population is a distinguishing feature of persons who spontaneously resolved an HCV infection. This finding, previously considered characteristic only of patients with HCV-associated lymphoproliferative disorders, suggests that the B cell clones potentially involved in clearance of the virus may also be those susceptible to abnormal expansion. PMID- 21980501 TI - Changes in early cortical visual processing predict enhanced reactivity in deaf individuals. AB - Individuals with profound deafness rely critically on vision to interact with their environment. Improvement of visual performance as a consequence of auditory deprivation is assumed to result from cross-modal changes occurring in late stages of visual processing. Here we measured reaction times and event-related potentials (ERPs) in profoundly deaf adults and hearing controls during a speeded visual detection task, to assess to what extent the enhanced reactivity of deaf individuals could reflect plastic changes in the early cortical processing of the stimulus. We found that deaf subjects were faster than hearing controls at detecting the visual targets, regardless of their location in the visual field (peripheral or peri-foveal). This behavioural facilitation was associated with ERP changes starting from the first detectable response in the striate cortex (C1 component) at about 80 ms after stimulus onset, and in the P1 complex (100-150 ms). In addition, we found that P1 peak amplitudes predicted the response times in deaf subjects, whereas in hearing individuals visual reactivity and ERP amplitudes correlated only at later stages of processing. These findings show that long-term auditory deprivation can profoundly alter visual processing from the earliest cortical stages. Furthermore, our results provide the first evidence of a co-variation between modified brain activity (cortical plasticity) and behavioural enhancement in this sensory-deprived population. PMID- 21980502 TI - Impaired CD4 T cell memory response to Streptococcus pneumoniae precedes CD4 T cell depletion in HIV-infected Malawian adults. AB - OBJECTIVE: Invasive pneumococcal disease (IPD) is a leading cause of morbidity and mortality in HIV-infected African adults. CD4 T cell depletion may partially explain this high disease burden but those with relatively preserved T cell numbers are still at increased risk of IPD. This study evaluated the extent of pneumococcal-specific T cell memory dysfunction in asymptomatic HIV infection early on in the evolution of the disease. METHODS: Peripheral blood mononuclear cells were isolated from asymptomatic HIV-infected and HIV-uninfected Malawian adults and stained to characterize the underlying degree of CD4 T cell immune activation, senescence and regulation. Pneumococcal-specific T cell proliferation, IFN-gamma, IL-17 production and CD154 expression was assessed using flow cytometry and ELISpot. RESULTS: We find that in asymptomatic HIV infected Malawian adults, there is considerable immune disruption with an increase in activated and senescent CD4+CD38+PD-1+ and CD4+CD25(high)Foxp3+ Treg cells. In the context of high pneumococcal exposure and therefore immune stimulation, show a failure in pneumococcal-specific memory T cell proliferation, skewing of T cell cytokine production with preservation of interleukin-17 but decreased interferon-gamma responses, and failure of activated T cells to express the co-stimulatory molecule CD154. CONCLUSION: Asymptomatic HIV-infected Malawian adults show early signs of pneumococcal- specific immune dysregulation with a shift in the balance of CD4 memory, T helper 17 cells and Treg. Together these data offer a mechanistic understanding of how antigen-specific T cell dysfunction occurs prior to T cell depletion and may explain the early susceptibility to IPD in those with relatively preserved CD4 T cell numbers. PMID- 21980503 TI - Peripheral CLOCK regulates target-tissue glucocorticoid receptor transcriptional activity in a circadian fashion in man. AB - CONTEXT AND OBJECTIVE: Circulating cortisol fluctuates diurnally under the control of the "master" circadian CLOCK, while the peripheral "slave" counterpart of the latter regulates the transcriptional activity of the glucocorticoid receptor (GR) at local glucocorticoid target tissues through acetylation. In this manuscript, we studied the effect of CLOCK-mediated GR acetylation on the sensitivity of peripheral tissues to glucocorticoids in humans. DESIGN AND PARTICIPANTS: We examined GR acetylation and mRNA expression of GR, CLOCK-related and glucocorticoid-responsive genes in peripheral blood mononuclear cells (PBMCs) obtained at 8 am and 8 pm from 10 healthy subjects, as well as in PBMCs obtained in the morning and cultured for 24 hours with exposure to 3-hour hydrocortisone pulses every 6 hours. We used EBV-transformed lymphocytes (EBVLs) as non synchronized controls. RESULTS: GR acetylation was higher in the morning than in the evening in PBMCs, mirroring the fluctuations of circulating cortisol in reverse phase. All known glucocorticoid-responsive genes tested responded as expected to hydrocortisone in non-synchronized EBVLs, however, some of these genes did not show the expected diurnal mRNA fluctuations in PBMCs in vivo. Instead, their mRNA oscillated in a Clock- and a GR acetylation-dependent fashion in naturally synchronized PBMCs cultured ex vivo in the absence of the endogenous glucocorticoid, suggesting that circulating cortisol might prevent circadian GR acetylation-dependent effects in some glucocorticoid-responsive genes in vivo. CONCLUSIONS: Peripheral CLOCK-mediated circadian acetylation of the human GR may function as a target-tissue, gene-specific counter regulatory mechanism to the actions of diurnally fluctuating cortisol, effectively decreasing tissue sensitivity to glucocorticoids in the morning and increasing it at night. PMID- 21980504 TI - Neurochemical architecture of the central complex related to its function in the control of grasshopper acoustic communication. AB - The central complex selects and coordinates the species- and situation-specific song production in acoustically communicating grasshoppers. Control of sound production is mediated by several neurotransmitters and modulators, their receptors and intracellular signaling pathways. It has previously been shown that muscarinic cholinergic excitation in the central complex promotes sound production whereas both GABA and nitric oxide/cyclic GMP signaling suppress its performance. The present immunocytochemical and pharmacological study investigates the question whether GABA and nitric oxide mediate inhibition of sound production independently. Muscarinic ACh receptors are expressed by columnar output neurons of the central complex that innervate the lower division of the central body and terminate in the lateral accessory lobes. GABAergic tangential neurons that innervate the lower division of the central body arborize in close proximity of columnar neurons and thus may directly inhibit these central complex output neurons. A subset of these GABAergic tangential neurons accumulates cyclic GMP following the release of nitric oxide from neurites in the upper division of the central body. While sound production stimulated by muscarine injection into the central complex is suppressed by co-application of sodium nitroprusside, picrotoxin-stimulated singing was not affected by co application of this nitric oxide donor, indicating that nitric oxide mediated inhibition requires functional GABA signaling. Hence, grasshopper sound production is controlled by processing of information in the lower division of the central body which is subject to modulation by nitric oxide released from neurons in the upper division. PMID- 21980505 TI - Nociceptive afferents to the premotor neurons that send axons simultaneously to the facial and hypoglossal motoneurons by means of axon collaterals. AB - It is well known that the brainstem premotor neurons of the facial nucleus and hypoglossal nucleus coordinate orofacial nociceptive reflex (ONR) responses. However, whether the brainstem PNs receive the nociceptive projection directly from the caudal spinal trigeminal nucleus is still kept unclear. Our present study focuses on the distribution of premotor neurons in the ONR pathways of rats and the collateral projection of the premotor neurons which are involved in the brainstem local pathways of the orofacial nociceptive reflexes of rat. Retrograde tracer Fluoro-gold (FG) or FG/tetramethylrhodamine-dextran amine (TMR-DA) were injected into the VII or/and XII, and anterograde tracer biotinylated dextran amine (BDA) was injected into the caudal spinal trigeminal nucleus (Vc). The tracing studies indicated that FG-labeled neurons receiving BDA-labeled fibers from the Vc were mainly distributed bilaterally in the parvicellular reticular formation (PCRt), dorsal and ventral medullary reticular formation (MdD, MdV), supratrigeminal nucleus (Vsup) and parabrachial nucleus (PBN) with an ipsilateral dominance. Some FG/TMR-DA double-labeled premotor neurons, which were observed bilaterally in the PCRt, MdD, dorsal part of the MdV, peri-motor nucleus regions, contacted with BDA-labeled axonal terminals and expressed c-fos protein-like immunoreactivity which induced by subcutaneous injection of formalin into the lip. After retrograde tracer wheat germ agglutinated horseradish peroxidase (WGA HRP) was injected into VII or XII and BDA into Vc, electron microscopic study revealed that some BDA-labeled axonal terminals made mainly asymmetric synapses on the dendritic and somatic profiles of WGA-HRP-labeled premotor neurons. These data indicate that some premotor neurons could integrate the orofacial nociceptive input from the Vc and transfer these signals simultaneously to different brainstem motonuclei by axonal collaterals. PMID- 21980506 TI - Discovery and genomic characterization of a novel ovine partetravirus and a new genotype of bovine partetravirus. AB - Partetravirus is a recently described group of animal parvoviruses which include the human partetravirus, bovine partetravirus and porcine partetravirus (previously known as human parvovirus 4, bovine hokovirus and porcine hokovirus respectively). In this report, we describe the discovery and genomic characterization of partetraviruses in bovine and ovine samples from China. These partetraviruses were detected by PCR in 1.8% of bovine liver samples, 66.7% of ovine liver samples and 71.4% of ovine spleen samples. One of the bovine partetraviruses detected in the present samples is phylogenetically distinct from previously reported bovine partetraviruses and likely represents a novel genotype. The ovine partetravirus is a novel partetravirus and phylogenetically most related to the bovine partetraviruses. The genome organization is conserved amongst these viruses, including the presence of a putative transmembrane protein encoded by an overlapping reading frame in ORF2. Results from the present study provide further support to the classification of partetraviruses as a separate genus in Parvovirinae. PMID- 21980507 TI - Amelioration of hypertriglyceridemia with hypo-alpha-cholesterolemia in LPL deficient mice by hematopoietic cell-derived LPL. AB - BACKGROUND: Macrophage-derived lipoprotein lipase (LPL) has been shown uniformly to promote atherosclerotic lesion formation while the extent to which it affects plasma lipid and lipoprotein levels varies in wild-type and hypercholesterolemic mice. It is known that high levels of LPL in the bulk of adipose tissue and skeletal muscle would certainly mask the contribution of macrophage LPL to metabolism of plasma lipoprotein. Therefore, we chose LPL deficient (LPL-/-) mice with severe hypertriglyceridemia as an alternative model to assess the role of macrophage LPL in plasma lipoprotein metabolism via bone marrow transplant, through which LPL will be produced mainly by hematopoietic cell-derived macrophages. METHODS AND RESULTS: Hypertriglyceridemic LPL-/- mice were lethally irradiated, then transplanted with bone marrow from wild-type (LPL+/+) or LPL-/- mice, respectively. Sixteen weeks later, LPL+/+ ->LPL-/- mice displayed significant reduction in plasma levels of triglyceride and cholesterol (408+/ 44.9 vs. 2.7+/-0.5*103 and 82.9+/-7.1 vs. 229.1+/-30.6 mg/dl, p<0.05, respectively), while a 2.7-fold increase in plasma high density lipoprotein- cholesterol (p<0.01) was observed, compared with LPL-/-->LPL-/- control mice. The clearance rate for the oral fat load test in LPL+/+ ->LPL-/- mice was faster than that in LPL-/-->LPL-/- mice, but slower than that in wild-type mice. Liver triglyceride content in LPL+/+->LPL-/- mice was also significantly increased, compared with LPL-/-->LPL-/- mice (6.8+/-0.7 vs. 4.6+/-0.5 mg/g wet tissue, p<0.05, n = 6). However, no significant change was observed in the expression levels of genes involved in hepatic lipid metabolism between the two groups. CONCLUSIONS: Hematopoietic cell-derived LPL could efficiently ameliorate severe hypertriglyceridemia and hypo-alpha-cholesterolemia at the compensation of increased triglyceride content of liver in LPL-/- mice. PMID- 21980508 TI - Automatic target recognition based on cross-plot. AB - Automatic target recognition that relies on rapid feature extraction of real-time target from photo-realistic imaging will enable efficient identification of target patterns. To achieve this objective, Cross-plots of binary patterns are explored as potential signatures for the observed target by high-speed capture of the crucial spatial features using minimal computational resources. Target recognition was implemented based on the proposed pattern recognition concept and tested rigorously for its precision and recall performance. We conclude that Cross-plotting is able to produce a digital fingerprint of a target that correlates efficiently and effectively to signatures of patterns having its identity in a target repository. PMID- 21980509 TI - The transcription factor Ndt80 does not contribute to Mrr1-, Tac1-, and Upc2 mediated fluconazole resistance in Candida albicans. AB - The pathogenic yeast Candida albicans can develop resistance to the widely used antifungal agent fluconazole, which inhibits ergosterol biosynthesis, by the overexpression of genes encoding multidrug efflux pumps or ergosterol biosynthesis enzymes. Zinc cluster transcription factors play a central role in the transcriptional regulation of drug resistance. Mrr1 regulates the expression of the major facilitator MDR1, Tac1 controls the expression of the ABC transporters CDR1 and CDR2, and Upc2 regulates ergosterol biosynthesis (ERG) genes. Gain-of-function mutations in these transcription factors result in constitutive overexpression of their target genes and are responsible for fluconazole resistance in many clinical C. albicans isolates. The transcription factor Ndt80 contributes to the drug-induced upregulation of CDR1 and ERG genes and also binds to the MDR1 and CDR2 promoters, suggesting that it is an important component of all major transcriptional mechanisms of fluconazole resistance. However, we found that Ndt80 is not required for the induction of MDR1 and CDR2 expression by inducing chemicals. CDR2 was even partially derepressed in ndt80Delta mutants, indicating that Ndt80 is a repressor of CDR2 expression. Hyperactive forms of Mrr1, Tac1, and Upc2 promoted overexpression of MDR1, CDR1/CDR2, and ERG11, respectively, with the same efficiency in the presence and absence of Ndt80. Mrr1- and Tac1-mediated fluconazole resistance was even slightly enhanced in ndt80Delta mutants compared to wild-type cells. These results demonstrate that Ndt80 is dispensable for the constitutive overexpression of Mrr1, Tac1, and Upc2 target genes and the increased fluconazole resistance of strains that have acquired activating mutations in these transcription factors. PMID- 21980510 TI - A glutathione peroxidase, intracellular peptidases and the TOR complexes regulate peptide transporter PEPT-1 in C. elegans. AB - The intestinal peptide transporter PEPT-1 in Caenorhabditis elegans is a rheogenic H(+)-dependent carrier responsible for the absorption of di- and tripeptides. Transporter-deficient pept-1(lg601) worms are characterized by impairments in growth, development and reproduction and develop a severe obesity like phenotype. The transport function of PEPT-1 as well as the influx of free fatty acids was shown to be dependent on the membrane potential and on the intracellular pH homeostasis, both of which are regulated by the sodium-proton exchanger NHX-2. Since many membrane proteins commonly function as complexes, there could be proteins that possibly modulate PEPT-1 expression and function. A systematic RNAi screening of 162 genes that are exclusively expressed in the intestine combined with a functional transport assay revealed four genes with homologues existing in mammals as predicted PEPT-1 modulators. While silencing of a glutathione peroxidase surprisingly caused an increase in PEPT-1 transport function, silencing of the ER to Golgi cargo transport protein and of two cytosolic peptidases reduced PEPT-1 transport activity and this even corresponded with lower PEPT-1 protein levels. These modifications of PEPT-1 function by gene silencing of homologous genes were also found to be conserved in the human epithelial cell line Caco-2/TC7 cells. Peptidase inhibition, amino acid supplementation and RNAi silencing of targets of rapamycin (TOR) components in C. elegans supports evidence that intracellular peptide hydrolysis and amino acid concentration are a part of a sensing system that controls PEPT-1 expression and function and that involves the TOR complexes TORC1 and TORC2. PMID- 21980511 TI - RAD51C germline mutations in breast and ovarian cancer cases from high-risk families. AB - BRCA1 and BRCA2 are the most well-known breast cancer susceptibility genes. Additional genes involved in DNA repair have been identified as predisposing to breast cancer. One such gene, RAD51C, is essential for homologous recombination repair. Several likely pathogenic RAD51C mutations have been identified in BRCA1- and BRCA2-negative breast and ovarian cancer families. We performed complete sequencing of RAD51C in germline DNA of 286 female breast and/or ovarian cancer cases with a family history of breast and ovarian cancers, who had previously tested negative for mutations in BRCA1 and BRCA2. We screened 133 breast cancer cases, 119 ovarian cancer cases, and 34 with both breast and ovarian cancers. Fifteen DNA sequence variants were identified; including four intronic, one 5' UTR, one promoter, three synonymous, and six non-synonymous variants. None were truncating. The in-silico SIFT and Polyphen programs were used to predict possible pathogenicity of the six non-synonomous variants based on sequence conservation. G153D and T287A were predicted to be likely pathogenic. Two additional variants, A126T and R214C alter amino acids in important domains of the protein such that they could be pathogenic. Two-hybrid screening and immunoblot analyses were performed to assess the functionality of these four non synonomous variants in yeast. The RAD51C-G153D protein displayed no detectable interaction with either XRCC3 or RAD51B, and RAD51C-R214C displayed significantly decreased interaction with both XRCC3 and RAD51B (p<0.001). Immunoblots of RAD51C Gal4 activation domain fusion peptides showed protein levels of RAD51C-G153D and RAD51C-R214C that were 50% and 60% of the wild-type, respectively. Based on these data, the RAD51C-G153D variant is likely to be pathogenic, while the RAD51C- R214C variant is hypomorphic of uncertain pathogenicity. These results provide further support that RAD51C is a rare breast and ovarian cancer susceptibility gene. PMID- 21980512 TI - Excitotoxicity triggered by Neurobasal culture medium. AB - Neurobasal defined culture medium has been optimized for survival of rat embryonic hippocampal neurons and is now widely used for many types of primary neuronal cell culture. Therefore, we were surprised that routine medium exchange with serum- and supplement-free Neurobasal killed as many as 50% of postnatal hippocampal neurons after a 4 h exposure at day in vitro 12-15. Minimal Essential Medium (MEM), in contrast, produced no significant toxicity. Detectable Neurobasal-induced neuronal death occurred with as little as 5 min exposure, measured 24 h later. D-2-Amino-5-phosphonovalerate (D-APV) completely prevented Neurobasal toxicity, implicating direct or indirect N-methyl-D-aspartate (NMDA) receptor-mediated neuronal excitotoxicity. Whole-cell recordings revealed that Neurobasal but not MEM directly activated D-APV-sensitive currents similar in amplitude to those gated by 1 uM glutamate. We hypothesized that L-cysteine likely mediates the excitotoxic effects of Neurobasal incubation. Although the original published formulation of Neurobasal contained only 10 uM L-cysteine, commercial recipes contain 260 uM, a concentration in the range reported to activate NMDA receptors. Consistent with our hypothesis, 260 uM L-cysteine in bicarbonate-buffered saline gated NMDA receptor currents and produced toxicity equivalent to Neurobasal. Although NMDA receptor-mediated depolarization and Ca2+ influx may support survival of young neurons, NMDA receptor agonist effects on development and survival should be considered when employing Neurobasal culture medium. PMID- 21980513 TI - GSTP1 DNA methylation and expression status is indicative of 5-aza-2' deoxycytidine efficacy in human prostate cancer cells. AB - DNA methylation plays an important role in carcinogenesis and the reversibility of this epigenetic modification makes it a potential therapeutic target. To date, DNA methyltransferase inhibitors (DNMTi) have not demonstrated clinical efficacy in prostate cancer, with one of the major obstacles being the inability to monitor drug activity during the trial. Given the high frequency and specificity of GSTP1 DNA methylation in prostate cancer, we investigated whether GSTP1 is a useful marker of DNMTi treatment efficacy. LNCaP prostate cancer cells were treated with 5-aza-2'-deoxycytidine (5-aza-CdR) either with a single high dose (5 20 uM), every alternate day (0.1-10 uM) or daily (0.005-2.5 uM). A daily treatment regimen with 5-aza-CdR was optimal, with significant suppression of cell proliferation achieved with doses of 0.05 uM or greater (p<0.0001) and induction of cell death from 0.5 uM (p<0.0001). In contrast, treatment with a single high dose of 20 uM 5-aza-CdR inhibited cell proliferation but was not able to induce cell death. Demethylation of GSTP1 was observed with doses of 5-aza-CdR that induced significant suppression of cell proliferation (>= 0.05 uM). Re expression of the GSTP1 protein was observed only at doses of 5-aza-CdR (>= 0.5 uM) associated with induction of cell death. Treatment of LNCaP cells with a more stable DNMTi, Zebularine required at least a 100-fold higher dose (>= 50 uM) to inhibit proliferation and was less potent in inducing cell death, which corresponded to a lack of GSTP1 protein re-expression. We have shown that GSTP1 DNA methylation and protein expression status is correlated with DNMTi treatment response in prostate cancer cells. Since GSTP1 is methylated in nearly all prostate cancers, our results warrant its testing as a marker of epigenetic therapy response in future clinical trials. We conclude that the DNA methylation and protein expression status of GSTP1 are good indicators of DNMTi efficacy. PMID- 21980514 TI - Dopamine-induced plasticity, phospholipase D (PLD) activity and cocaine-cue behavior depend on PLD-linked metabotropic glutamate receptors in amygdala. AB - Cocaine-cue associations induce synaptic plasticity with long lasting molecular and cellular changes in the amygdala, a site crucial for cue-associated memory mechanisms. The underlying neuroadaptations can include marked alterations in signaling via dopamine (DA) receptors (DRs) and metabotropic glutamate (Glu) receptors (mGluRs). Previously, we reported that DR antagonists blocked forms of synaptic plasticity in amygdala slices of Sprague-Dawley rats withdrawn from repeated cocaine administration. In the present study, we investigated synaptic plasticity induced by exogenous DA and its dependence on mGluR signaling and a potential role for phospholipase D (PLD) as a downstream element linked to mGluR and DR signaling. Utilizing a modified conditioned place preference (CPP) paradigm as a functional behavioral measure, we studied the neurophysiological effects after two-weeks to the last cocaine conditioning. We recorded, electrophysiologically, a DR-induced synaptic potentiation in the basolateral to lateral capsula central amygdala (BLA-lcCeA) synaptic pathway that was blocked by antagonists of group I mGluRs, particularly, the PLD-linked mGluR. In addition, we observed 2-2.5 fold increase in PLD expression and 3.7-fold increase in basal PLD enzyme activity. The enhanced PLD activity could be further stimulated (9.3 fold) by a DA D1-like (D1/5R) receptor agonist, and decreased to control levels by mGluR1 and PLD-linked mGluR antagonists. Diminished CPP was observed by infusion of a PLD-linked mGluR antagonist, PCCG-13, in the amygdala 15 minutes prior to testing, two weeks after the last cocaine injection. These results imply a functional interaction between D1/5Rs, group I mGluRs via PLD in the amygdala synaptic plasticity associated with cocaine-cues. PMID- 21980515 TI - First-step mutations for adaptation at elevated temperature increase capsid stability in a virus. AB - The relationship between mutation, protein stability and protein function plays a central role in molecular evolution. Mutations tend to be destabilizing, including those that would confer novel functions such as host-switching or antibiotic resistance. Elevated temperature may play an important role in preadapting a protein for such novel functions by selecting for stabilizing mutations. In this study, we test the stability change conferred by single mutations that arise in a G4-like bacteriophage adapting to elevated temperature. The vast majority of these mutations map to interfaces between viral coat proteins, suggesting they affect protein-protein interactions. We assess their effects by estimating thermodynamic stability using molecular dynamic simulations and measuring kinetic stability using experimental decay assays. The results indicate that most, though not all, of the observed mutations are stabilizing. PMID- 21980516 TI - Understanding lignin-degrading reactions of ligninolytic enzymes: binding affinity and interactional profile. AB - Previous works have demonstrated that ligninolytic enzymes mediated effective degradation of lignin wastes. The degrading ability greatly relied on the interactions of ligninolytic enzymes with lignin. Ligninolytic enzymes mainly contain laccase (Lac), lignin peroxidase (LiP) and manganese peroxidase (MnP). In the present study, the binding modes of lignin to Lac, LiP and MnP were systematically determined, respectively. Robustness of these modes was further verified by molecular dynamics (MD) simulations. Residues GLU460, PRO346 and SER113 in Lac, residues ARG43, ALA180 and ASP183 in LiP and residues ARG42, HIS173 and ARG177 in MnP were most crucial in binding of lignin, respectively. Interactional analyses showed hydrophobic contacts were most abundant, playing an important role in the determination of substrate specificity. This information is an important contribution to the details of enzyme-catalyzed reactions in the process of lignin biodegradation, which can be used as references for designing enzyme mutants with a better lignin-degrading activity. PMID- 21980517 TI - The Neurospora crassa TOB complex: analysis of the topology and function of Tob38 and Tob37. AB - The TOB or SAM complex is responsible for assembling several proteins into the mitochondrial outer membrane, including all beta-barrel proteins. We have identified several forms of the complex in Neurospora crassa. One form contains Tob55, Tob38, and Tob37; another contains these three subunits plus the Mdm10 protein; while additional complexes contain only Tob55. As previously shown for Tob55, both Tob37 and Tob38 are essential for viability of the organism. Mitochondria deficient in Tob37 or Tob38 have reduced ability to assemble beta barrel proteins. The function of two hydrophobic domains in the C-terminal region of the Tob37 protein was investigated. Mutant Tob37 proteins lacking either or both of these regions are able to restore viability to cells lacking the protein. One of the domains was found to anchor the protein to the outer mitochondrial membrane but was not necessary for targeting or association of the protein with mitochondria. Examination of the import properties of mitochondria containing Tob37 with deletions of the hydrophobic domains reveals that the topology of Tob37 may be important for interactions between specific classes of beta-barrel precursors and the TOB complex. PMID- 21980518 TI - Bioenergetic profiling of zebrafish embryonic development. AB - Many debilitating conditions are linked to bioenergetic defects. Developing screens to probe the genetic and/or chemical basis for such links has proved intractable. Furthermore, there is a need for a physiologically relevant assay of bioenergetics in whole organisms, especially for early stages in life where perturbations could increase disease susceptibility with aging. Thus, we asked whether we could screen bioenergetics and mitochondrial function in the developing zebrafish embryo. We present a multiplexed method to assay bioenergetics in zebrafish embryos from the blastula period (3 hours post fertilization, hpf) through to hatching (48 hpf). In proof of principle experiments, we measured respiration and acid extrusion of developing zebrafish embryos. We quantified respiratory coupling to various bioenergetic functions by using specific pharmacological inhibitors of bioenergetic pathways. We demonstrate that changes in the coupling to ATP turnover and proton leak are correlated with developmental stage. The multiwell format of this assay enables the user to screen for the effects of drugs and environmental agents on bioenergetics in the zebrafish embryo with high sensitivity and reproducibility. PMID- 21980519 TI - Identification of the CRE-1 cellulolytic regulon in Neurospora crassa. AB - BACKGROUND: In filamentous ascomycete fungi, the utilization of alternate carbon sources is influenced by the zinc finger transcription factor CreA/CRE-1, which encodes a carbon catabolite repressor protein homologous to Mig1 from Saccharomyces cerevisiae. In Neurospora crassa, deletion of cre-1 results in increased secretion of amylase and beta-galactosidase. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that a strain carrying a deletion of cre-1 has increased cellulolytic activity and increased expression of cellulolytic genes during growth on crystalline cellulose (Avicel). Constitutive expression of cre-1 complements the phenotype of a N. crassa Deltacre-1 strain grown on Avicel, and also results in stronger repression of cellulolytic protein secretion and enzyme activity. We determined the CRE-1 regulon by investigating the secretome and transcriptome of a Deltacre-1 strain as compared to wild type when grown on Avicel versus minimal medium. Chromatin immunoprecipitation-PCR of putative target genes showed that CRE-1 binds to only some adjacent 5'-SYGGRG-3' motifs, consistent with previous findings in other fungi, and suggests that unidentified additional regulatory factors affect CRE-1 binding to promoter regions. Characterization of 30 mutants containing deletions in genes whose expression level increased in a Deltacre-1 strain under cellulolytic conditions identified novel genes that affect cellulase activity and protein secretion. CONCLUSIONS/SIGNIFICANCE: Our data provide comprehensive information on the CRE-1 regulon in N. crassa and contribute to deciphering the global role of carbon catabolite repression in filamentous ascomycete fungi during plant cell wall deconstruction. PMID- 21980520 TI - Gender differences in myogenic regulation along the vascular tree of the gerbil cochlea. AB - Regulation of cochlear blood flow is critical for hearing due to its exquisite sensitivity to ischemia and oxidative stress. Many forms of hearing loss such as sensorineural hearing loss and presbyacusis may involve or be aggravated by blood flow disorders. Animal experiments and clinical outcomes further suggest that there is a gender preference in hearing loss, with males being more susceptible. Autoregulation of cochlear blood flow has been demonstrated in some animal models in vivo, suggesting that similar to the brain, blood vessels supplying the cochlea have the ability to control flow within normal limits, despite variations in systemic blood pressure. Here, we investigated myogenic regulation in the cochlear blood supply of the Mongolian gerbil, a widely used animal model in hearing research. The cochlear blood supply originates at the basilar artery, followed by the anterior inferior cerebellar artery, and inside the inner ear, by the spiral modiolar artery and the radiating arterioles that supply the capillary beds of the spiral ligament and stria vascularis. Arteries from male and female gerbils were isolated and pressurized using a concentric pipette system. Diameter changes in response to increasing luminal pressures were recorded by laser scanning microscopy. Our results show that cochlear vessels from male and female gerbils exhibit myogenic regulation but with important differences. Whereas in male gerbils, both spiral modiolar arteries and radiating arterioles exhibited pressure-dependent tone, in females, only radiating arterioles had this property. Male spiral modiolar arteries responded more to L-NNA than female spiral modiolar arteries, suggesting that NO-dependent mechanisms play a bigger role in the myogenic regulation of male than female gerbil cochlear vessels. PMID- 21980521 TI - The persistent circulation of enterovirus 71 in People's Republic of China: causing emerging nationwide epidemics since 2008. AB - Emerging epidemics of hand-foot-and-mouth disease (HFMD) associated with enterovirus 71 (EV71) has become a serious concern in mainland China. It caused 126 and 353 fatalities in 2008 and 2009, respectively. The epidemiologic and pathogenic data of the outbreak collected from national laboratory network and notifiable disease surveillance system. To understand the virological evolution of this emerging outbreak, 326 VP1 gene sequences of EV71 detected in China from 1987 to 2009 were collected for genetic analyses. Evidence from both traditional and molecular epidemiology confirmed that the recent HFMD outbreak was an emerging one caused by EV71 of subgenotype C4. This emerging HFMD outbreak is associated with EV71 of subgenotype C4, circulating persistently in mainland China since 1998, but not attributed to the importation of new genotype. Originating from 1992, subgenotype C4 has been the predominant genotype since 1998 in mainland China, with an evolutionary rate of 4.6~4.8*10-3 nucleotide substitutions/site/year. The phylogenetic analysis revealed that the majority of the virus during this epidemic was the most recent descendant of subgenotype C4 (clade C4a). It suggests that the evolution might be one of the potential reasons for this native virus to cause the emerging outbreak in China. However, strong negative selective pressure on VP1 protein of EV71 suggested that immune escape might not be the evolving strategy of EV71, predicting a light future for vaccine development. Nonetheless, long-term antigenic and genetic surveillance is still necessary for further understanding. PMID- 21980522 TI - Mesenchymal stem cells exhibit firm adhesion, crawling, spreading and transmigration across aortic endothelial cells: effects of chemokines and shear. AB - Mesenchymal stem cells (MSCs) have anti-inflammatory and immunosuppressive properties and may be useful in the therapy of diseases such as arteriosclerosis. MSCs have some ability to traffic into inflamed tissues, however to exploit this therapeutically their migratory mechanisms need to be elucidated. This study examines the interaction of murine MSCs (mMSCs) with, and their migration across, murine aortic endothelial cells (MAECs), and the effects of chemokines and shear stress. The interaction of mMSCs with MAECs was examined under physiological flow conditions. mMSCs showed lack of interaction with MAECs under continuous flow. However, when the flow was stopped (for 10 min) and then started, mMSCs adhered and crawled on the endothelial surface, extending fine microvillous processes (filopodia). They then spread extending pseudopodia in multiple directions. CXCL9 significantly enhanced the percentage of mMSCs adhering, crawling and spreading and shear forces markedly stimulated crawling and spreading. CXCL9, CXCL16, CCL20 and CCL25 significantly enhanced transendothelial migration across MAECs. The transmigrated mMSCs had down-regulated receptors CXCR3, CXCR6, CCR6 and CCR9. This study furthers the knowledge of MSC transendothelial migration and the effects of chemokines and shear stress which is of relevance to inflammatory diseases such as arteriosclerosis. PMID- 21980523 TI - Evaluation of pulsed-FRAP and conventional-FRAP for determination of protein mobility in prokaryotic cells. AB - BACKGROUND: Macromolecule mobility is often quantified with Fluorescence Recovery After Photobleaching (FRAP). Throughout literature a wide range of diffusion coefficients for GFP in the cytoplasm of Escherichia coli (3 to 14 um2/s) is reported using FRAP-based approaches. In this study, we have evaluated two of these methods: pulsed-FRAP and "conventional"-FRAP. PRINCIPAL FINDINGS: To address the question whether the apparent discrepancy in the diffusion data stems from methodological differences or biological variation, we have implemented and compared the two techniques on bacteria grown and handled in the same way. The GFP diffusion coefficients obtained under normal osmotic conditions and upon osmotic upshift were very similar for the different techniques. CONCLUSIONS: Our analyses indicate that the wide range of values reported for the diffusion coefficient of GFP in live cells are due to experimental conditions and/or biological variation rather than methodological differences. PMID- 21980524 TI - Dephosphorylated NSSR1 is induced by androgen in mouse epididymis and phosphorylated NSSR1 is increased during sperm maturation. AB - NSSR1 (Neural salient serine/arginine rich protein 1, alternatively SRp38) is a newly identified RNA splicing factor and predominantly expressed in neural tissues. Here, by Western blot analysis and immunofluorescent staining, we showed that the expression of dephosphorylated NSSR1 increased significantly during development of the caput epididymis. In adult mice, phosphorylated NSSR1 was mainly expressed in the apical side of epithelial cells, and dephosphorylated NSSR1 in caput epididymis was upregulated in a testosterone dependent manner. In addition, subcellular immunoreactive distribution of NSSR1 varied in different regions of the epididymis. With respect to the sperm, phosphorylated NSSR1 was detected in the mid-piece of the tail as well as the acrosome. Furthermore, NSSR1 was released from the sperm head during the capacitation and acrosome reaction. These findings for the first time provide the evidence for the potential roles of NSSR1 in sperm maturation and fertilization. PMID- 21980525 TI - VEGFR2 translocates to the nucleus to regulate its own transcription. AB - Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) is the major mediator of the angiogenic effects of VEGF. In addition to its well known role as a membrane receptor that activates multiple signaling pathways, VEGFR2 also has a nuclear localization. However, what VEGFR2 does in the nucleus is still unknown. In the present report we show that, in endothelial cells, nuclear VEGFR2 interacts with several nuclear proteins, including the Sp1, a transcription factor that has been implicated in the regulation of genes needed for angiogenesis. By in vivo chromatin immunoprecipitation (ChIP) assays, we found that VEGFR2 binds to the Sp1-responsive region of the VEGFR2 proximal promoter. These results were confirmed by EMSA assays, using the same region of the VEGFR2 promoter. Importantly, we show that the VEGFR2 DNA binding is directly linked to the transcriptional activation of the VEGFR2 promoter. By reporter assays, we found that the region between -300/-116 relative to the transcription start site is essential to confer VEGFR2-dependent transcriptional activity. It was previously described that nuclear translocation of the VEGFR2 is dependent on its activation by VEGF. In agreement, we observed that the binding of VEGFR2 to DNA requires VEGF activation, being blocked by Bevacizumab and Sunitinib, two anti-angiogenic agents that inhibit VEGFR2 activation. Our findings demonstrate a new mechanism by which VEGFR2 activates its own promoter that could be involved in amplifying the angiogenic response. PMID- 21980526 TI - The N-terminal, polybasic region is critical for prion protein neuroprotective activity. AB - Several lines of evidence suggest that the normal form of the prion protein, PrP(C), exerts a neuroprotective activity against cellular stress or toxicity. One of the clearest examples of such activity is the ability of wild-type PrP(C) to suppress the spontaneous neurodegenerative phenotype of transgenic mice expressing a deleted form of PrP (Delta32-134, called F35). To define domains of PrP involved in its neuroprotective activity, we have analyzed the ability of several deletion mutants of PrP (Delta23-31, Delta23-111, and Delta23-134) to rescue the phenotype of Tg(F35) mice. Surprisingly, all of these mutants displayed greatly diminished rescue activity, although Delta23-31 PrP partially suppressed neuronal loss when expressed at very high levels. Our results pinpoint the N-terminal, polybasic domain as a critical determinant of PrP(C) neuroprotective activity, and suggest that identification of molecules interacting with this region will provide important clues regarding the normal function of the protein. Small molecule ligands targeting this region may also represent useful therapeutic agents for treatment of prion diseases. PMID- 21980527 TI - Gene expression analysis reveals the cell cycle and kinetochore genes participating in ischemia reperfusion injury and early development in kidney. AB - BACKGROUND: The molecular mechanisms that mediate the ischemia-reperfusion (I/R) injury in kidney are not completely understood. It is also largely unknown whether such mechanisms overlap with those governing the early development of kidney. METHODOLOGY/PRINCIPAL FINDINGS: We performed gene expression analysis to investigate the transcriptome changes during regeneration after I/R injury in the rat (0 hr, 6 hr, 24 hr, and 120 hr after reperfusion) and early development of mouse kidney (embryonic day 16 p.c. and postnatal 1 and 7 day). Pathway analysis revealed a wide spectrum of molecular functions that may participate in the regeneration and developmental processes of kidney as well as the functional association between them. While the genes associated with cell cycle, immunity, inflammation, and apoptosis were globally activated during the regeneration after I/R injury, the genes encoding various transporters and metabolic enzymes were down-regulated. We also observed that these injury-associated molecular functions largely overlap with those of early kidney development. In particular, the up regulation of kinases and kinesins with roles in cell division was common during regeneration and early developmental kidney as validated by real-time PCR and immunohistochemistry. CONCLUSIONS: In addition to the candidate genes whose up regulation constitutes an overlapping expression signature between kidney regeneration and development, this study lays a foundation for studying the functional relationship between two biological processes. PMID- 21980528 TI - Egr3 dependent sympathetic target tissue innervation in the absence of neuron death. AB - Nerve Growth Factor (NGF) is a target tissue derived neurotrophin required for normal sympathetic neuron survival and target tissue innervation. NGF signaling regulates gene expression in sympathetic neurons, which in turn mediates critical aspects of neuron survival, axon extension and terminal axon branching during sympathetic nervous system (SNS) development. Egr3 is a transcription factor regulated by NGF signaling in sympathetic neurons that is essential for normal SNS development. Germline Egr3-deficient mice have physiologic dysautonomia characterized by apoptotic sympathetic neuron death and abnormal innervation to many target tissues. The extent to which sympathetic innervation abnormalities in the absence of Egr3 is caused by altered innervation or by neuron death during development is unknown. Using Bax-deficient mice to abrogate apoptotic sympathetic neuron death in vivo, we show that Egr3 has an essential role in target tissue innervation in the absence of neuron death. Sympathetic target tissue innervation is abnormal in many target tissues in the absence of neuron death, and like NGF, Egr3 also appears to effect target tissue innervation heterogeneously. In some tissues, such as heart, spleen, bowel, kidney, pineal gland and the eye, Egr3 is essential for normal innervation, whereas in other tissues such as lung, stomach, pancreas and liver, Egr3 appears to have little role in innervation. Moreover, in salivary glands and heart, two tissues where Egr3 has an essential role in sympathetic innervation, NGF and NT-3 are expressed normally in the absence of Egr3 indicating that abnormal target tissue innervation is not due to deregulation of these neurotrophins in target tissues. Taken together, these results clearly demonstrate a role for Egr3 in mediating sympathetic target tissue innervation that is independent of neuron survival or neurotrophin deregulation. PMID- 21980529 TI - Nogo-A expression in the brain of mice with cerebral malaria. AB - Cerebral malaria (CM) is associated with a high rate of transient or persistent neurological sequelae. Nogo-A, a protein that is highly expressed in the endoplasmic reticulum (ER) of the mammalian central nervous system (CNS), is involved in neuronal regeneration and synaptic plasticity in the injured CNS. The current study investigates the role of Nogo-A in the course of experimental CM. C57BL/6J mice were infected with Plasmodium berghei ANKA blood stages. Brain homogenates of mice with different clinical severity levels of CM, infected animals without CM and control animals were analyzed for Nogo-A up-regulation by Western blotting and immunohistochemistry. Brain regions with Nogo-A upregulation were evaluated by transmission electron microscopy. Densitometric analysis of Western blots yielded a statistically significant upregulation of Nogo-A in mice showing moderate to severe CM. The number of neurons and oligodendrocytes positive for Nogo-A did not differ significantly between the studied groups. However, mice with severe CM showed a significantly higher number of cells with intense Nogo-A staining in the brain stem. In this region ultrastructural alterations of the ER were regularly observed. Nogo-A is upregulated during the early course of experimental CM. In the brain stem of severely affected animals increased Nogo-A expression and ultrastructural changes of the ER were observed. These data indicate a role of Nogo-A in neuronal stress response during experimental CM. PMID- 21980530 TI - The flexible nature of unconscious cognition. AB - The cognitive signature of unconscious processes is hotly debated recently. Generally, consciousness is thought to mediate flexible, adaptive and goal directed behavior, but in the last decade unconscious processing has rapidly gained ground on traditional conscious territory. In this study we demonstrate that the scope and impact of unconscious information on behavior and brain activity can be modulated dynamically on a trial-by-trial basis. Participants performed a Go/No-Go experiment in which an unconscious (masked) stimulus preceding a conscious target could be associated with either a Go or No-Go response. Importantly, the mapping of stimuli onto these actions varied on a trial-by-trial basis, preventing the formation of stable associations and hence the possibility that unconscious stimuli automatically activate these control actions. By eliminating stimulus-response associations established through practice we demonstrate that unconscious information can be processed in a flexible and adaptive manner. In this experiment we show that the same unconscious stimulus can have a substantially different effect on behavior and (prefrontal) brain activity depending on the rapidly changing task context in which it is presented. This work suggests that unconscious information processing shares many sophisticated characteristics (including flexibility and context specificity) with its conscious counterpart. PMID- 21980531 TI - Lateral diffusion on tubular membranes: quantification of measurements bias. AB - Single Particle Tracking (SPT) is a powerful technique for the analysis of the lateral diffusion of the lipid and protein components of biological membranes. In neurons, SPT allows the study of the real-time dynamics of receptors for neurotransmitters that diffuse continuously in and out synapses. In the simplest case where the membrane is flat and is parallel to the focal plane of the microscope the analysis of diffusion from SPT data is relatively straightforward. However, in most biological samples the membranes are curved, which complicates analysis and may lead to erroneous conclusions as for the mode of lateral diffusion. Here we considered the case of lateral diffusion in tubular membranes, such as axons, dendrites or the neck of dendritic spines. Monte Carlo simulations allowed us to evaluate the error in diffusion coefficient (D) calculation if the curvature is not taken into account. The underestimation is determined by the diameter of the tubular surface, the frequency of image acquisition and the degree of mobility itself. We found that projected trajectories give estimates that are 25 to 50% lower than the real D in case of 2D-SPT over the tubular surface. The use of 3D-SPT improved the measurements if the frequency of image acquisition was fast enough in relation to the mobility of the molecules and the diameter of the tube. Nevertheless, the calculation of D from the components of displacements in the axis of the tubular structure gave accurate estimate of D, free of geometrical artefacts. We show the application of this approach to analyze the diffusion of a lipid on model tubular membranes and of a membrane bound GFP on neurites from cultured rat hippocampal neurons. PMID- 21980532 TI - Pandemic influenza due to pH1N1/2009 virus: estimation of infection burden in Reunion Island through a prospective serosurvey, austral winter 2009. AB - BACKGROUND: To date, there is little information that reflects the true extent of spread of the pH1N1/2009v influenza pandemic at the community level as infection often results in mild or no clinical symptoms. This study aimed at assessing through a prospective study, the attack rate of pH1N1/2009 virus in Reunion Island and risk factors of infection, during the 2009 season. METHODOLOGY/PRINCIPAL FINDINGS: A serosurvey was conducted during the 2009 austral winter, in the frame of a prospective population study. Pairs of sera were collected from 1687 individuals belonging to 772 households, during and after passage of the pandemic wave. Antibodies to pH1N1/2009v were titered using the hemagglutination inhibition assay (HIA) with titers >= 1/40 being considered positive. Seroprevalence during the first two weeks of detection of pH1N1/2009v in Reunion Island was 29.8% in people under 20 years of age, 35.6% in adults (20 59 years) and 73.3% in the elderly (>= 60 years) (P<0.0001). Baseline corrected cumulative incidence rates, were 42.9%, 13.9% and 0% in these age groups respectively (P<0.0001). A significant decline in antibody titers occurred soon after the passage of the epidemic wave. Seroconversion rates to pH1N1/2009 correlated negatively with age: 63.2%, 39.4% and 16.7%, in each age group respectively (P<0.0001). Seroconversion occurred in 65.2% of individuals who were seronegative at inclusion compared to 6.8% in those who were initially seropositive. CONCLUSIONS: Seroincidence of pH1N1/2009v infection was three times that estimated from clinical surveillance, indicating that almost two thirds of infections occurring at the community level have escaped medical detection. People under 20 years of age were the most affected group. Pre-epidemic titers >= 1/40 prevented seroconversion and are likely protective against infection. A concern was raised about the long term stability of the antibody responses. PMID- 21980533 TI - The demographic and socioeconomic factors predictive for populations at high-risk for La Crosse virus infection in West Virginia. AB - Although a large body of literature exists for the environmental risk factors for La Crosse virus (LACV) transmission, the demographic and socioeconomic risk factors for developing LACV infection have not been investigated. Therefore, this study investigated the demographic and socioeconomic risk factors for LACV infection in West Virginia from 2003 to 2007, using two forward stepwise discriminant analyses. The discriminant analyses were used to evaluate a number of demographic and socioeconomic factors for their ability to predict: 1) those census tracts with at least one reported case of LACV infection versus those census tracts with no reported cases of LACV infection and 2) to evaluate significantly high-risk clusters for LACV infection versus significantly low-risk clusters for LACV infection. In the first model, a high school education diploma or a general education diploma or less and a lower housing densitywere found to be predictive of those census tracts with at least one case of LACV infection. A high school or a general education diploma or less, lower housing density, and housing built in 1969 and earlier were all found to be predictive of those census tracts displaying high-risk clusters versus census tracts displaying low-risk clusters in the second model. The cluster discriminant analysis was found to be more predictive than the census tract discriminant analysis as indicated by the Eigenvalues, canonical correlation, and grouping accuracy. The results of this study indicate that socioeconomically disadvantaged populations are at the highest risk for LACV infection and should be a focus of LACV infection prevention efforts. PMID- 21980534 TI - Rem2-targeted shRNAs reduce frequency of miniature excitatory postsynaptic currents without altering voltage-gated Ca2+ currents. AB - Ca2+ influx through voltage-gated Ca2+ channels (VGCCs) plays important roles in neuronal cell development and function. Rem2 is a member of the RGK (Rad, Rem, Rem2, Gem/Kir) subfamily of small GTPases that confers potent inhibition upon VGCCs. The physiologic roles of RGK proteins, particularly in the brain, are poorly understood. Rem2 was implicated in synaptogenesis through an RNAi screen and proposed to regulate Ca2+ homeostasis in neurons. To test this hypothesis and uncover physiological roles for Rem2 in the brain, we investigated the molecular mechanisms by which Rem2 knockdown affected synaptogenesis and Ca2+ homeostasis in cultured rat hippocampal neurons. Expression of a cocktail of shRNAs targeting rat Rem2 (rRem2) reduced the frequency of miniature excitatory postsynaptic currents (mEPSCs) measured 10 d after transfection (14 d in vitro), but did not affect mEPSC amplitude. VGCC current amplitude after rRem2-targeted knockdown was not different from that in control cells, however, at either 4 or 10 d post transfection. Co-expression of a human Rem2 that was insensitive to the shRNAs targeting rRem2 was unable to prevent the reduction in mEPSC frequency after rRem2-targeted knockdown. Over-expression of rRem2 resulted in 50% reduction in VGCC current, but neither the mEPSC frequency nor amplitude was affected. Taken together, the observed effects upon synaptogenesis after shRNA treatment are more likely due to mechanisms other than modulation of VGCCs and Ca2+ homeostasis, and may be independent of Rem2. In addition, our results reveal a surprising lack of contribution of VGCCs to synaptogenesis during early development in cultured hippocampal neurons. PMID- 21980535 TI - KAP degradation by calpain is associated with CK2 phosphorylation and provides a novel mechanism for cyclosporine A-induced proximal tubule injury. AB - The use of cyclosporine A (CsA) is limited by its severe nephrotoxicity that includes reversible vasoconstrictor effects and proximal tubule cell injury, the latter associated whith chronic kidney disease progression. The mechanisms of CsA induced tubular injury, mainly on the S3 segment, have not been completely elucidated. Kidney androgen-regulated protein (KAP) is exclusively expressed in kidney proximal tubule cells, interacts with the CsA-binding protein cyclophilin B and its expression diminishes in kidneys of CsA-treated mice. Since we reported that KAP protects against CsA toxicity in cultured proximal tubule cells, we hypothesized that low KAP levels found in kidneys of CsA-treated mice might correlate with proximal tubule cell injury. To test this hypothesis, we used KAP Tg mice developed in our laboratory and showed that these mice are more resistant to CsA-induced tubular injury than control littermates. Furthermore, we found that calpain, which was activated by CsA in cell cultures and kidney, is involved in KAP degradation and observed that phosphorylation of serine and threonine residues found in KAP PEST sequences by protein kinase CK2 enhances KAP degradation by calpain. Moreover, we also observed that CK2 inhibition protected against CsA-induced cytotoxicity. These findings point to a novel mechanism for CsA-induced kidney toxicity that might be useful in developing therapeutic strategies aimed at preventing tubular cell damage while maintaining the immunosuppressive effects of CsA. PMID- 21980536 TI - Ameliorative effects of dimetylthiourea and N-acetylcysteine on nanoparticles induced cyto-genotoxicity in human lung cancer cells-A549. AB - We study the ameliorative potential of dimetylthiourea (DMTU), an OH* radical trapper and N-acetylcysteine (NAC), a glutathione precursor/H2O2 scavenger against titanium dioxide nanoparticles (TiO2-NPs) and multi-walled carbon nanotubes (MWCNTs) induced cyto-genotoxicity in cultured human lung cancer cells A549. Cytogenotoxicity was induced by exposing the cells to selected concentrations (10 and 50 ug/ml) of either of TiO2-NPs or MWCNTs for 24 h. Anti cytogenotoxicity effects of DMTU and NAC were studied in two groups, i.e., treatment of 30 minutes prior to toxic insult (short term exposure), while the other group received DMTU and NAC treatment during nanoparticles exposure, i.e., 24 h (long term exposure). Investigations were carried out for cell viability, generation of reactive oxygen species (ROS), micronuclei (MN), and expression of markers of oxidative stress (HSP27, CYP2E1), genotoxicity (P53) and CYP2E1 dependent n- nitrosodimethylamine-demethylase (NDMA-d) activity. In general, the treatment of both DMTU and NAC was found to be effective significantly against TiO2-NPs and MWCNTs induced cytogenotoxicity in A549 cells. Long-term treatment of DMTU and NAC during toxic insults has shown better prevention than short-term pretreatment. Although, cells responded significantly to both DMTU and NAC, but responses were chemical specific. In part, TiO2-NPs induced toxic responses were mediated through OH* radicals generation and reduction in the antioxidant defense system. While in the case of MWCNTs, adverse effects were primarily due to altering/hampering the enzymatic antioxidant system. Data indicate the applicability of human lung cancer cells-A549 as a pre-screening tool to identify the target specific prophylactic and therapeutic potential of drugs candidate molecules against nanoparticles induced cellular damages. PMID- 21980537 TI - Effects of single nucleotide polymorphisms on human N-acetyltransferase 2 structure and dynamics by molecular dynamics simulation. AB - BACKGROUND: Arylamine N-acetyltransferase 2 (NAT2) is an important catalytic enzyme that metabolizes the carcinogenic arylamines, hydrazine drugs and chemicals. This enzyme is highly polymorphic in different human populations. Several polymorphisms of NAT2, including the single amino acid substitutions R64Q, I114T, D122N, L137F, Q145P, R197Q, and G286E, are classified as slow acetylators, whereas the wild-type NAT2 is classified as a fast acetylator. The slow acetylators are often associated with drug toxicity and efficacy as well as cancer susceptibility. The biological functions of these 7 mutations have previously been characterized, but the structural basis behind the reduced catalytic activity and reduced protein level is not clear. METHODOLOGY/PRINCIPAL FINDINGS: We performed multiple molecular dynamics simulations of these mutants as well as NAT2 to investigate the structural and dynamical effects throughout the protein structure, specifically the catalytic triad, cofactor binding site, and the substrate binding pocket. None of these mutations induced unfolding; instead, their effects were confined to the inter-domain, domain 3 and 17-residue insert region, where the flexibility was significantly reduced relative to the wild-type. Structural effects of these mutations propagate through space and cause a change in catalytic triad conformation, cofactor binding site, substrate binding pocket size/shape and electrostatic potential. CONCLUSIONS/SIGNIFICANCE: Our results showed that the dynamical properties of all the mutant structures, especially in inter-domain, domain 3 and 17-residue insert region were affected in the same manner. Similarly, the electrostatic potential of all the mutants were altered and also the functionally important regions such as catalytic triad, cofactor binding site, and substrate binding pocket adopted different orientation and/or conformation relative to the wild-type that may affect the functions of the mutants. Overall, our study may provide the structural basis for reduced catalytic activity and protein level, as was experimentally observed for these polymorphisms. PMID- 21980538 TI - Reassortant H9N2 influenza viruses containing H5N1-like PB1 genes isolated from black-billed magpies in Southern China. AB - H9N2 influenza A viruses have become endemic in different types of terrestrial poultry and wild birds in Asia, and are occasionally transmitted to humans and pigs. To evaluate the role of black-billed magpies (Pica pica) in the evolution of influenza A virus, we conducted two epidemic surveys on avian influenza viruses in wild black-billed magpies in Guangxi, China in 2005 and characterized three isolated black-billed magpie H9N2 viruses (BbM viruses). Phylogenetic analysis indicated that three BbM viruses were almost identical with 99.7 to 100% nucleotide homology in their whole genomes, and were reassortants containing BJ94 like (Ck/BJ/1/94) HA, NA, M, and NS genes, SH/F/98-like (Ck/SH/F/98) PB2, PA, and NP genes, and H5N1-like (Ck/YN/1252/03, clade 1) PB1 genes. Genetic analysis showed that BbM viruses were most likely the result of multiple reassortments between co-circulating H9N2-like and H5N1-like viruses, and were genetically different from other H9N2 viruses because of the existence of H5N1-like PB1 genes. Genotypical analysis revealed that BbM viruses evolved from diverse sources and belonged to a novel genotype (B46) discovered in our recent study. Molecular analysis suggested that BbM viruses were likely low pathogenic reassortants. However, results of our pathogenicity study demonstrated that BbM viruses replicated efficiently in chickens and a mammalian mouse model but were not lethal for infected chickens and mice. Antigenic analysis showed that BbM viruses were antigenic heterologous with the H9N2 vaccine strain. Our study is probably the first report to document and characterize H9N2 influenza viruses isolated from black-billed magpies in southern China. Our results suggest that black-billed magpies were susceptible to H9N2 influenza viruses, which raise concerns over possible transmissions of reassortant H9N2 viruses among poultry and wild birds. PMID- 21980539 TI - Multi-locus estimates of population structure and migration in a fence lizard hybrid zone. AB - A hybrid zone between two species of lizards in the genus Sceloporus (S. cowlesi and S. tristichus) on the Mogollon Rim in Arizona provides a unique opportunity to study the processes of lineage divergence and merging. This hybrid zone involves complex interactions between 2 morphologically and ecologically divergent subspecies, 3 chromosomal groups, and 4 mitochondrial DNA (mtDNA) clades. The spatial patterns of divergence between morphology, chromosomes and mtDNA are discordant, and determining which of these character types (if any) reflects the underlying population-level lineages that are of interest has remained impeded by character conflict. The focus of this study is to estimate the number of populations interacting in the hybrid zone using multi-locus nuclear data, and to then estimate the migration rates and divergence time between the inferred populations. Multi-locus estimates of population structure and gene flow were obtained from 12 anonymous nuclear loci sequenced for 93 specimens of Sceloporus. Population structure estimates support two populations, and this result is robust to changes to the prior probability distribution used in the Bayesian analysis and the use of spatially-explicit or non-spatial models. A coalescent analysis of population divergence suggests that gene flow is high between the two populations, and that the timing of divergence is restricted to the Pleistocene. The hybrid zone is more accurately described as involving two populations belonging to S. tristichus, and the presence of S. cowlesi mtDNA haplotypes in the hybrid zone is an anomaly resulting from mitochondrial introgression. PMID- 21980540 TI - Innovative partnerships for drug discovery against neglected diseases. PMID- 21980541 TI - Central Asia's hidden burden of neglected tropical diseases. PMID- 21980542 TI - Visceral leishmaniasis and arsenic: an ancient poison contributing to antimonial treatment failure in the Indian subcontinent? PMID- 21980543 TI - The 2007 Rift Valley fever outbreak in Sudan. AB - Rift Valley fever (RVF) is a neglected, emerging, mosquito-borne disease with severe negative impact on human and animal health and economy. RVF is caused by RVF virus (RVFV) affecting humans and a wide range of animals. The virus is transmitted through bites from mosquitoes and exposure to viremic blood, body fluids, or tissues of infected animals. During 2007 a large RVF outbreak occurred in Sudan with a total of 747 confirmed human cases including 230 deaths (case fatality 30.8%); although it has been estimated 75,000 were infected. It was most severe in White Nile, El Gezira, and Sennar states near to the White Nile and the Blue Nile Rivers. Notably, RVF was not demonstrated in livestock until after the human cases appeared and unfortunately, there are no records or reports of the number of affected animals or deaths. Ideally, animals should serve as sentinels to prevent loss of human life, but the situation here was reversed. Animal contact seemed to be the most dominant risk factor followed by animal products and mosquito bites. The Sudan outbreak followed an unusually heavy rainfall in the country with severe flooding and previous studies on RVF in Sudan suggest that RVFV is endemic in parts of Sudan. An RVF outbreak results in human disease, but also large economic loss with an impact beyond the immediate influence on the directly affected agricultural producers. The outbreak emphasizes the need for collaboration between veterinary and health authorities, entomologists, environmental specialists, and biologists, as the best strategy towards the prevention and control of RVF. PMID- 21980544 TI - Quantifying the emergence of dengue in Hanoi, Vietnam: 1998-2009. AB - BACKGROUND: An estimated 2.4 billion people live in areas at risk of dengue transmission, therefore the factors determining the establishment of endemic dengue in areas where transmission suitability is marginal is of considerable importance. Hanoi, Vietnam is such an area, and following a large dengue outbreak in 2009, we set out to determine if dengue is emerging in Hanoi. METHODS AND PRINCIPAL FINDINGS: We undertook a temporal and spatial analysis of 25,983 dengue cases notified in Hanoi between 1998 and 2009. Age standardized incidence rates, standardized age of infection, and Standardized Morbidity Ratios (SMR) were calculated. A quasi-Poisson regression model was used to determine if dengue incidence was increasing over time. Wavelet analysis was used to explore the periodicity of dengue transmission and the association with climate variables. After excluding the two major outbreak years of 1998 and 2009 and correcting for changes in population age structure, we identified a significant annual increase in the incidence of dengue cases over the period 1999-2008 (incidence rate ratio = 1.38, 95% confidence interval = 1.20-1.58, p value = 0.002). The age of notified dengue cases in Hanoi is high, with a median age of 23 years (mean 26.3 years). After adjusting for changes in population age structure, there was no statistically significant change in the median or mean age of dengue cases over the period studied. Districts in the central, highly urban, area of Hanoi have the highest incidence of dengue (SMR>3). CONCLUSIONS: Hanoi is a low dengue transmission setting where dengue incidence has been increasing year on year since 1999. This trend needs to be confirmed with serological surveys, followed by studies to determine the underlying drivers of this emergence. Such studies can provide insights into the biological, demographic, and environmental changes associated with vulnerability to the establishment of endemic dengue. PMID- 21980545 TI - Scabies mite peritrophins are potential targets of human host innate immunity. AB - BACKGROUND: Pruritic scabies lesions caused by Sarcoptes scabiei burrowing in the stratum corneum of human skin facilitate opportunistic bacterial infections. Emerging resistance to current therapeutics emphasizes the need to identify novel targets for protective intervention. We have characterized several protein families located in the mite gut as crucial factors for host-parasite interactions. Among these multiple proteins inhibit human complement, presumably to avoid complement-mediated damage of gut epithelial cells. Peritrophins are major components of the peritrophic matrix often found in the gut of arthropods. We hypothesized that a peritrophin, if abundant in the scabies mite gut, could be an activator of complement. METHODOLOGY/PRINCIPAL FINDINGS: A novel full length scabies mite peritrophin (SsPTP1) was identified in a cDNA library from scabies mites. The amino acid sequence revealed four putative chitin binding domains (CBD). Recombinant expression of one CBD of the highly repetitive SsPTP1 sequence as TSP-hexaHis-fusion protein resulted in soluble protein, which demonstrated chitin binding activity in affinity chromatography assays. Antibodies against a recombinant SsPTP1 fragment were used to immunohistochemically localize native SsPTP1 in the mite gut and in fecal pellets within the upper epidermis, co localizing with serum components such as host IgG and complement. Enzymatic deglycosylation confirmed strong N- and O-glycosylation of the native peritrophin. Serum incubation followed by immunoblotting with a monoclonal antibody against mannan binding lectin (MBL), the recognition molecule of the lectin pathway of human complement activation, indicated that MBL may specifically bind to glycosylated SsPTP1. CONCLUSIONS/SIGNIFICANCE: This study adds a new aspect to the accumulating evidence that complement plays a major role in scabies mite biology. It identifies a novel peritrophin localized in the mite gut as a potential target of the lectin pathway of the complement cascade. These initial findings indicate a novel role of scabies mite peritrophins in triggering a host innate immune response within the mite gut. PMID- 21980546 TI - Maternal serologic screening to prevent congenital toxoplasmosis: a decision analytic economic model. AB - OBJECTIVE: To determine a cost-minimizing option for congenital toxoplasmosis in the United States. METHODOLOGY/PRINCIPAL FINDINGS: A decision-analytic and cost minimization model was constructed to compare monthly maternal serological screening, prenatal treatment, and post-natal follow-up and treatment according to the current French (Paris) protocol, versus no systematic screening or perinatal treatment. Costs are based on published estimates of lifetime societal costs of developmental disabilities and current diagnostic and treatment costs. Probabilities are based on published results and clinical practice in the United States and France. One- and two-way sensitivity analyses are used to evaluate robustness of results. Universal monthly maternal screening for congenital toxoplasmosis with follow-up and treatment, following the French protocol, is found to be cost-saving, with savings of $620 per child screened. Results are robust to changes in test costs, value of statistical life, seroprevalence in women of childbearing age, fetal loss due to amniocentesis, and to bivariate analysis of test costs and incidence of primary T. gondii infection in pregnancy. Given the parameters in this model and a maternal screening test cost of $12, screening is cost-saving for rates of congenital infection above 1 per 10,000 live births. If universal testing generates economies of scale in diagnostic tools-lowering test costs to about $2 per test-universal screening is cost-saving at rates of congenital infection well below the lowest reported rates in the United States of 1 per 10,000 live births. CONCLUSION/SIGNIFICANCE: Universal screening according to the French protocol is cost saving for the US population within broad parameters for costs and probabilities. PMID- 21980547 TI - Histopathological changes and clinical responses of Buruli ulcer plaque lesions during chemotherapy: a role for surgical removal of necrotic tissue? AB - BACKGROUND: Buruli ulcer (BU) caused by Mycobacterium ulcerans is a necrotizing skin disease usually starting with a subcutaneous nodule or plaque, which may ulcerate and progress, if untreated, over months and years. During the currently recommended antibiotic treatment with rifampicin/streptomycin plaque lesions tend to ulcerate, often associated with retarded wound healing and prolonged hospital stays. METHODOLOGY/PRINCIPAL FINDINGS: Included in this study were twelve laboratory reconfirmed, HIV negative BU patients presenting with plaque lesions at the CDTUB in Allada, Benin. Punch biopsies for histopathological and immunohistochemical analysis were taken before start of treatment and after four to five weeks of treatment. Where excision or wound debridement was clinically indicated, the removed tissue was also analyzed. Based on clinical judgment, nine of the twelve patients enrolled in this study received limited surgical excision seven to 39 days after completion of chemotherapy, followed by skin grafting. Lesions of three patients healed without further intervention. Before treatment, plaque lesions were characterized by a destroyed subcutis with extensive necrosis without major signs of infiltration. After completion of antibiotic treatment partial infiltration of the affected tissue was observed, but large necrotic areas remained unchanged. CONCLUSION/SIGNIFICANCE: Our histopathological analyses show that ulceration of plaque lesions during antibiotic treatment do not represent a failure to respond to antimycobacterial treatment. Based on our results we suggest formal testing in a controlled clinical trial setting whether limited surgical excision of necrotic tissue favours wound healing and can reduce the duration of hospital stays. PMID- 21980548 TI - Proteomic analysis of human skin treated with larval schistosome peptidases reveals distinct invasion strategies among species of blood flukes. AB - BACKGROUND: Skin invasion is the initial step in infection of the human host by schistosome blood flukes. Schistosome larvae have the remarkable ability to overcome the physical and biochemical barriers present in skin in the absence of any mechanical trauma. While a serine peptidase with activity against insoluble elastin appears to be essential for this process in one species of schistosomes, Schistosoma mansoni, it is unknown whether other schistosome species use the same peptidase to facilitate entry into their hosts. METHODS: Recent genome sequencing projects, together with a number of biochemical studies, identified alternative peptidases that Schistosoma japonicum or Trichobilharzia regenti could use to facilitate migration through skin. In this study, we used comparative proteomic analysis of human skin treated with purified cercarial elastase, the known invasive peptidase of S. mansoni, or S. mansoni cathespin B2, a close homolog of the putative invasive peptidase of S. japonicum, to identify substrates of either peptidase. Select skin proteins were then confirmed as substrates by in vitro digestion assays. CONCLUSIONS: This study demonstrates that an S. mansoni ortholog of the candidate invasive peptidase of S. japonicum and T. regenti, cathepsin B2, is capable of efficiently cleaving many of the same host skin substrates as the invasive serine peptidase of S. mansoni, cercarial elastase. At the same time, identification of unique substrates and the broader species specificity of cathepsin B2 suggest that the cercarial elastase gene family amplified as an adaptation of schistosomes to human hosts. PMID- 21980549 TI - Soil-transmitted helminth infections among plantation sector schoolchildren in Sri Lanka: prevalence after ten years of preventive chemotherapy. AB - BACKGROUND: The plantation sector in Sri Lanka lags behind the rest of the country in terms of living conditions and health. In 1992, a sector-wide survey of children aged 3-12 years and women of reproductive age showed >90% prevalence of soil-transmitted helminth infections. Biannual mass de-worming targeting children aged 3-18 years started in 1994 and was continued until 2005. The present study was carried out to assess the status of infection four years after cessation of mass de-worming. METHODS/FINDINGS: A school-based cross-sectional survey was carried out. Faecal samples from approximately 20 children from each of 114 schools in five districts were examined using the modified Kato-Katz technique. Data regarding the school, the child's family and household sanitation were recorded after inspection of schools and households. Multivariate analysis was carried out using logistic regression, to identify risk factors for infection. Faecal samples were obtained from 1890 children. In 4/5 districts, >20% were infected with one or more helminth species. Overall combined prevalence was 29.0%; 11.6% had infections of moderate-heavy intensity. The commonest infection was Ascaris lumbricoides, present in all five districts, as was Trichuris trichiura. Hookworm was not detected in two districts. Multivariate analysis identified low altitude and maternal under-education as risk factors for all three infections. Poor household sanitation was identified as a risk factor for A. lumbricoides and hookworm, but not T. trichiura infections. CONCLUSIONS/SIGNIFICANCE: The results indicate that regular mass de-worming of plantation sector children should be resumed along with more emphasis on better sanitation and health education. They show that even after 10 years of mass chemotherapy, prevalence can bounce back after cessation of preventive chemotherapy, if the initial force of transmission is strong and other long-term control measures are not concomitantly implemented. PMID- 21980550 TI - A layman's view of problems with evolution theory. AB - This article had its origins in a letter of mine that was published in The Guardian, a UK newspaper.1 The Communicative & Integrative Biology (CIB) Editor in-Chief happened to read the letter and asked me whether I was prepared to write a short opinion article with the hope that it may stimulate wider discussion I somewhat reluctantly accepted. The reason for my hesitation is that I have no expertise whatsoever in Biology or evolution theory. I often read absurd comments by educated non-experts pontificating on my own topic of expertise and wonder why do they do it! Occasionally though, a complete non-expert such as a child asks questions which are so basic that they may confound even an expert. It is from this standpoint of "innocent ignorance" that my speculations may possibly be of some value to the readers of CIB. PMID- 21980551 TI - Integrating biological invasions, climate change and phenotypic plasticity. AB - Invasive species frequently change the ecosystems where they are introduced, e.g., by affecting species interactions and population densities of native species. We outline the connectedness of biological invasions, climate change and the phenomenon of phenotypic plasticity. Integrating these hot topics is important for understanding the biology of many species, their information transfer and general interactions with other organisms. One example where this is particularly true is the zooplankton species Daphnia lumholtzi, which has successfully invaded North America. The combination of a high thermal tolerance and a phenotypically plastic defense in D. lumholtzi might be responsible for its invasion success. Its morphological defense consists of rigid spines and is formed after sensory detecting the presence of native fish predators. The integration of biological invasions, climate change and phenotypic plasticity is an important goal for integrative biology. PMID- 21980552 TI - Control of luminescence from lantern shark (Etmopterus spinax) photophores. AB - The velvet belly lantern shark (Etmopterus spinax) is a common deep-sea shark that has been used, in the recent years, as a model for experimental studies on physiological control of shark luminescence. These studies demonstrated that, unlike any other luminous organism, the luminescence of this shark was under a dual control of hormones and neurotransmitters (or neuromodulators). This paper, by making a short review of histological and pharmacological results from these studies, aims to propose a first model of luminescence control in E. spinax. PMID- 21980553 TI - Reelin modulates cytoskeletal organization by regulating Rho GTPases. AB - The correct positioning of postmitotic neurons in the developing neocortex and other laminated brain structures requires the activation of a Reelin-lipoprotein receptor-Dab1 signaling cascade. The large glycoprotein Reelin is secreted by Cajal-Retzius pioneer neurons and bound by the apolipoprotein E receptor family members Apoer2 and Vldl receptor on responsive neurons and radial glia. This leads to the tyrosine phosphorylation of the cytoplasmic protein Disabled-1 (Dab1) by non-receptor tyrosine kinases of the Src family. Various signaling pathways downstream of Dab1 connect Reelin to the actin and microtubule cytoskeleton. Despite this knowledge, a comprehensive view linking the different cell-biological and biochemical actions of Reelin to its diverse physiological roles not only during neurodevelopment but also in the maintenance and functioning of the adult brain is still lacking. In this review, we discuss our finding that Reelin activates Rho GTPases in neurons in the light of other recent studies, which demonstrate a role of Reelin in Golgi organization, and suggest additional roles of Cdc42 activation by Reelin in radial glial cells of the developing cortex. PMID- 21980554 TI - Abnormal calcium homeostasis and protein folding stress at the ER: A common factor in familial and infectious prion disorders. AB - Prion-related disorders (PrDs) are caused by the accumulation of a misfolded and protease-resistant form of the cellular prion, leading to neuronal dysfunction and massive neuronal loss. In humans, PrDs have distinct etiologies including sporadic, infectious and familial forms, which present common clinical features; however, the possible existence of common neuropathogenic events are not known. Several studies suggest that alterations in protein folding and quality control mechanisms at the endoplasmic reticulum (ER) are a common factor involved in PrDs. However, the mechanism underlying ER dysfunction in PrDs remains unknown. We have recently reported that alterations in ER calcium homeostasis are common pathological events observed in both infectious and familial PrD models. Perturbation in calcium homeostasis directly correlated with the occurrence of ER stress and higher susceptibility to protein folding stress. We envision a model where alterations in ER function are central and common events underlying prion pathogenesis, leading to general alterations on protein homeostasis networks. PMID- 21980555 TI - Pulling rabbits to reveal the secrets of the prion protein. AB - The Prion protein (PrP) is a membrane-tethered glycoprotein that plays a central role in a unique class of neurodegenerative diseases that affect humans and other mammals. Prion diseases have genetic and sporadic origins, but their infectious nature sets them apart from other neurodegenerative disorders. According to the "protein-only" hypothesis, misfolded PrP conformers (prions) are responsible for both spongiform degeneration of the brain and disease transmissibility. Thus, understanding PrP conformational dynamics is key to developing effective therapies. Classic studies showing the different susceptibility to prion disease in mammals have recently found support in structural and transgenic studies with PrP from susceptible (mouse, hamster) and resistant (rabbit, horse, dog) animals. These studies identify key residues in PrP that determine both PrP structure and its propensity to acquire a beta-structure conformation proposed to be neurotoxic. PMID- 21980556 TI - Nucleolin: The most abundant multifunctional phosphoprotein of nucleolus. AB - Nucleolin is a multifunctional phosphoprotein ubiquitously distributed in the nucleolus, nucleus and cytoplasm of the cell. Nucleolin has a bipartite nuclear localization signal sequence and is conserved in animals, plants and yeast. Its levels are correlated with the rate of functional activity of the nucleolus in exponentially growing cells. Nucleolin contains intrinsic DNA and RNA helicase, nucleic-acid-dependent ATPase and self-cleaving activities. It binds RNA through its RNA recognition motifs. It regulates various aspects of DNA and RNA metabolism, chromatin structure, rDNA transcription, rRNA maturation, cytokinesis, nucleogenesis, cell proliferation and growth, the folding, maturation and ribosome assembly and nucleocytoplasmic transport of newly synthesized pre-RNAs. In this review we present an overview on nucleolin, its localization, structure and various functions. We also describe the discovery and important studies of nucleolin in plants. PMID- 21980557 TI - Sex and the public: Social eavesdropping, sperm competition risk and male mate choice. AB - Mate choice can be sensitive to social cues from neighboring individuals, e.g., animals can copy mate choice decisions. Males that are at risk of being copied by others may respond to this with reduced preference expression ("audience effects"). We review the various pathways by which sperm competition risk affects (1) male mate copying behavior and (2) audience effects. For example, a recent study suggests that males gather complex social information on rivals' sexual competitiveness (sexual activity and attractiveness to females) and respond with reduced expression of mating preferences only "when it matters," i.e., when a sexually competitive rival is present. PMID- 21980558 TI - Fine-tuning MAPK signaling in the brain: The role of MKP-1. AB - Mitogen-activated protein kinase (MAPK) signaling influences a variety of neuronal properties, including structural characteristics such as spine density, and physiological features like long-term potentiation. Spatiotemporal control of MAPK signaling is crucial to generate specific changes in neuronal physiology. However, while many studies have concentrated on the activation of MAPK signaling by trophic factors such as BDNF and neuronal activity, the mechanisms that lead to its termination have not been well described. Two recent reports begin to address this question by focusing on the role of the MAPK phosphatase, MKP-1, in neuronal function. The first study provides a cellular mechanism underlying MKP-1 action in the brain.1 The second study describes potential roles of MKP-1 during stress and major depression.2. PMID- 21980559 TI - Alternative splicing adds a new loop to the circadian clock. AB - Circadian clocks allow organisms to adjust multiple physiological and developmental processes in anticipation of daily and seasonal changes in the environment. At the molecular level these clocks consist of interlocked feedback loops, involving transcriptional activation and repression, but also post translational modifications. In a recently published work we provided evidence that PRMT5, a protein arginine methyl transferase, is part of a novel loop within the circadian clock of the plant Arabidopsis thaliana by regulating alternative splicing of key clock mRNAs. We also found evidence indicating that PRMT5 has a role in the regulation of alternative splicing and the circadian network in Drosophila melanogaster, although the clock connection in the latter is more elusive and seems to be at the output level. We conclude that alternative precursor messenger RNA (premRNA) splicing is part of the circadian program and could be a main actor in the fine-tuning of biological clocks. Here, we embrace the alternative splicing process as part of the circadian program and discuss the possibility that this mechanism is of fundamental relevance for the fine-tuning of biological clocks. PMID- 21980560 TI - A net-like structure with pores is observed during cell fusion induced by the receptor FGFRL1. AB - FGFRL1 is the fifth member of the fibroblast growth factor receptor (FGFR) family. Similar to the other members, it harbors three Ig loops in its extracellular domain, but in contrast to the other receptors, it lacks the intracellular protein tyrosine kinase domain that would be required for signaling by transphosphorylation. FGFRL1 is mainly found in the musculoskeletal system, where it appears to inhibit cell proliferation but to induce cell adhesion and differentiation. Mice with a targeted disruption of the FGFRL1 gene die during birth due to a malformed diaphragm muscle, which is not strong enough to inflate the lungs after birth. Expression of FGFRL1 is highly upregulated during the differentiation of myoblasts to multinucleated myotubes, suggesting an important role for FGFRL1 in cell-cell fusion. Recently we showed that FGFRL1 does indeed induce fusion of cultured cells into large syncytia. A reporter gene assay demonstrated that the third Ig domain and the transmembrane domain of FGFRL1 are both necessary and sufficient to fuse CHO cells into syncytia comprising several hundred nuclei. At the contact site, the fusing cells reveal a peculiar net-like structure with pores of about 1 um diameter. It is possible that these structures represent membrane areas with fusion pores that set in motion the cell-cell fusion process. FGFRL1 is the first mammalian protein that is capable of triggering cell-cell fusion in vitro. PMID- 21980561 TI - Geometrical ordering of DNA in bacteria. AB - The bacterium Caulobacter crescentus shows a remarkable spatial ordering of its chromosome that leads to a strong linear correlation between the position of genes on the chromosomal map and their spatial position in the cellular volume. In a recent study we have shown that a robust and universal geometrical ordering mechanism can explain this correlation. We demonstrated that self-avoidance of DNA, specific positioning of one or few DNA loci (such as origin or terminus) together with the action of DNA compaction proteins (that organize the chromosome into topological domains) are sufficient to get a linear arrangement of the chromosome along the cell axis. This configuration, however, only represents the population average. Individual cells can have DNA arrangements that deviate significantly from the mean configuration and that break left-right symmetry. Symmetry breaking is stronger for longer chromosomes. PMID- 21980562 TI - Leadership, collective motion and the evolution of migratory strategies. AB - Migration is a hallmark life history strategy of a diverse range of organisms, and also ubiquitous in ontogenic processes including normal embryonic development as well as tumor progression. In such scenarios, individual organisms/cells typically respond to long range (and often noisy) environmental cues. In addition, individuals may interact socially with one another leading to emergent group-level navigational abilities. Although much progress has been made in understanding the mechanisms of taxis, there is a lack of theoretical and quantitative understanding of how individuals trade-off information obtained through their own migratory ability and that via social interactions. Here, we discuss results and insights from a recent computational model developed to investigate the evolution of leadership and collective motion in migratory populations. It is shown that, for a broad range of parameter values, only a small proportion of the population gather directional information while the majority employ social cues alone. More generally, ecological conditions for the evolution of resident, solitary and collective migratory strategies are obtained. We discuss how consideration of both proximate and ultimate factors within the same framework may provide insights into preserving migratory patterns that are in grave danger due to anthropogenic pressures. PMID- 21980563 TI - Inhibition of unwinding and ATPase activities of Plasmodium falciparum Dbp5/DDX19 homolog. AB - We have recently reported the isolation and characterization of Plasmodium falciparum Dbp5/DDX19 homolog PfD66 and the results indicate that it contains ATP dependent bipolar DNA and RNA unwinding activity, intrinsic nucleic acid dependent ATPase and RNA-binding activities. In the present study we report the effect of a number of compounds such as actinomycin D, aphidicolin, camptothecin, cyclophosphamide, 4',6'-di-amidino-2-phenylindole (DAPI), daunorubicin, distamycin, ethidium bromide, ellipticine, genistein, mitoxantrone, nalidixic acid, netropsin, nogalamycin, novobiocin and VP-16 on the DNA unwinding and ATPase activities of PfD66. The results indicate that DAPI, ethidium bromide, netropsin and nogalamycin efficiently inhibited the helicase and ATPase activities of PfD66. These studies will make an important contribution in understanding the mechanism of DNA unwinding by Plasmodium falciparum helicase PfD66. PMID- 21980564 TI - Axon selection: From a polarized cytoplasm to a migrating neuron. AB - The shape of a neuron supplies valuable clues as to its function. Neurons typically extend a single long, thin axon, which will transmit signals and several shorter and thicker dendrites, which will receive signals. The understanding of the means by which neurons acquire a polarized morphology is a fundamental issue in developmental neurobiology. The current view suggests that axon selection involves a stochastic mechanism. However, new data suggest that a polarized cytoplasm not only determines the position of neurite emergence, but also sets the conditions for morphological polarization. In vertebrates, neurons migrate before establishing their final morphology. Recent work shows that the polarized cytoplasm also determines how neurons migrate. Thus, neuronal migration might influence the processes by which neurons form an axon. PMID- 21980565 TI - Gene ontology analysis of the centrosome proteomes of Drosophila and human. AB - The centrosome is a complex cell organelle in higher eukaryotic cells that functions in microtubule organization and is integrated into major cellular signaling pathways.1-3 For example, a tight link exists between cell cycle regulation and centrosome duplication, as centrosome numbers must be precisely controlled to ensure high fidelity of chromosome segregation.4 The analysis of the centrosome's protein composition provides the opportunity for a better understanding of centrosome function and to identify possible links to cellular signaling pathways.5,6 Our proteomics study of the Drosophila centrosome recently identified 251 centrosome candidate proteins that we subsequently characterized by RNAi in Drosophila SL2 cells and classified according to their function in centrosome duplication/segregation, structure maintenance and cell cycle regulation.7 Interestingly, functional characterization of their human orthologous proteins revealed the highest functional conservation in the process of centrosome duplication and separation. To analyze functional and biochemical interdependencies further, we carried out an analysis of the gene ontology (GO) annotation of the identified Drosophila centrosome proteins, as well as of the human centrosome proteome.5 The GO analysis of the group of proteins that did not show a centrosome, chromosome segregation or cell cycle related phenotype in our RNAi assays suggests that these molecules may constitute linker proteins to other cellular signaling pathways. Furthermore, the results of our GO analysis of components of the human and of the Drosophila centrosome reflect the somatic and embryonic origin, respectively, of the isolated centrosomes, implicating the Drosophila centrosome proteins in developmental signaling and cell differentiation. PMID- 21980566 TI - Nuclear translocation of RanGAP1 coincides with virtual nuclear envelope breakdown in fission yeast meiosis. AB - In higher eukaryotes, mitosis proceeds with nuclear envelope breakdown (NEBD) and disassembly of the nuclear pore complex (NPC); this is designated "open" mitosis. On the other hand, in many fungi, mitosis and chromosome segregation takes place without NEBD; this is designated "closed" mitosis. In a recent study on Schizosaccharomyces pombe, a closed mitosis organism, we reported a novel phenomenon that is equivalent to NEBD: a mixing of nuclear proteins and cytoplasmic proteins occurred transiently for a few minutes in meiosis without physical breakdown of the nuclear envelope. We designated this event virtual nuclear envelope breakdown (V-NEBD). In S. pombe, nuclear translocation of Rna1, a RanGAP1 homolog in S. pombe, occurs during meiosis, and this translocation of Rna1 leads to collapse of the Ran-GTP gradient across the nuclear envelope and occurs coincidently with V-NEBD. Here, we describe possible roles of RanGAP1 in V NEBD in S. pombe and provide insights into the roles V-NEBD may play in meiosis. PMID- 21980567 TI - Pantomime in great apes: Evidence and implications. AB - We recently demonstrated, by mining observational data, that forest-living orangutans can communicate using gestures that qualify as pantomime.1 Pantomimes, like other iconic gestures, physically resemble their referents.2,3 More elaborately, pantomimes involve enacting their referents.4 Holding thumb and finger together at the lips and blowing between them to mean "balloon" is one example.5 Here we sketch evidence of pantomime in other great apes, methodological concerns and sophisticated cognitive capabilities that great ape pantomimes suggest. PMID- 21980568 TI - The role of dopamine and serotonin in conditioned food aversion learning in the honeybee. AB - For most animals, eating entails the risk of being poisoned. Learning how to identify foods with toxins is an important mechanism that reduces the risk of poisoning. While conditioned food aversions have been studied in vertebrates for over 50 years, the neural circuits underlying this form of learning have been difficult to elucidate because of their complexity. Insects, such as fruit flies and honeybees, are important models for the study of the neural mechanisms of learning and memory, but conditioned food aversions have not yet been reported from either species. My collaborators and I recently established that the honeybee has the ability to learn to avoid odors associated with toxins in food using two independent neural pathways. In these experiments, we found that honeybees can learn to associate scents with toxins that they can pre-ingestively detect using their proboscis. This form of learning is primarily mediated by the neurotransmitter, dopamine. We also found a second mechanism: bees can learn to avoid odors associated with the malaise caused by ingesting toxins. This form of learning is mediated by serotonin. Our data are the first to show that two different mechanisms account for conditioned food aversions in insects. PMID- 21980569 TI - Event-related potentials in response to subjects' own names: A comparison between humans and a chimpanzee. AB - The sound of one's own name is one of the most salient auditory environmental stimuli. Several studies of human brain potentials have revealed some characteristic waveforms when we hear our own names. In a recent work, we investigated event-related potentials (ERPs) in a female chimpanzee and demonstrated that the ERP pattern generated when she heard her own name differed from that generated when she heard other sounds. However, her ERPs did not exhibit a prominent positive shift around 300 ms (P3) in response to her own name, as has been repeatedly shown in studies of human ERPs. The present study collected comparative data for adult humans using basically the same procedure as that used in our previous study of the chimpanzee. These results also revealed no prominent P3 to the human subjects' own names. The lack of increased P3 is therefore likely due to our experimental protocol, in which we presented the subject's own name relatively frequently. In contrast, our results revealed prominent negativity to the subject's own name at around 500 ms in the chimpanzee and around 200 ms in human subjects. This may indicate that initial orientation to the sound of one's own name is delayed in the chimpanzee. PMID- 21980570 TI - Tunneling-nanotube: A new way of cell-cell communication. AB - Tunneling-nanotubes (TNTs) are a kind of cell-cell communication when cells are under stress. We hypothesize that insulted cells use TNTs as a highway to transfer materials and energy to healthy cells. TNTs transfer cellular compartments, such as endoplasmic reticulum (ER), mitochondria, Golgi and endosomes. Some cytotoxic particles, such as intracellular and extracellular amyloid beta (Abeta), scrapie prion protein (PrP(Sc)) and human immunodeficiency virus (HIV)-1, are suggested to transfer with TNTs as well. p53, epidermal growth factor receptor (EGFR), Akt, phosphoinositide 3-kinase (PI3K) and mTOR are important for TNT induction. However, currently our understanding of TNTs is greatly limited. Further studies need to be done to improve our knowledge of the mechanisms and physiological functions of TNTs. PMID- 21980571 TI - N-cadherin regulates radial glial fiber-dependent migration of cortical locomoting neurons. AB - During cerebral cortical development, post-mitotic neurons exhibit a multi-step migration. The locomotion mode covers most of the neuronal migration path. Although for many decades, locomoting neurons have been known to migrate along radial glial fibers, how the cortical locomoting neurons attach to and migrate along radial glial fibers was largely unknown. We recently reported that N cadherin is required for cortical neuronal migration in vivo. Knockdown or dominant negative inhibition of N-cadherin results in severe neuronal migration defects. Furthermore, suppression of Rab5-dependent endocytosis increases cell surface levels of N-cadherin and perturbs neuronal migration. We showed here that N-cadherin overexpression, which would mimic Rab5 suppression, weakly suppressed neuronal migration, suggesting that excess N-cadherin also disturbs neuronal migration. Interestingly, however, N-cadherin knockdown and overexpression in neurons resulted in different morphologies. While N-cadherin-overexpressing cells closely attached to the radial glial fibers similar to control or Rab5-knockdown cells, N-cadherin knockdown weakened the attachment as the average distance between the soma and radial glial fibers was significantly increased. Taken together, these findings suggest that N-cadherin controls the neuronal attachment to radial glial fibers and that N-cadherin-mediated adhesion complexes are reconstituted through Rab GTPases-dependent endocytic pathways to maintain the proper surface N-cadherin level and to promote neuronal migration. PMID- 21980572 TI - Ca-binding and spectral properties of the common region of surface-exposed Lig proteins of leptospira. AB - Pathogenic Leptospira protein LigA and LigB are conserved at the N-terminal sequence. In our earlier report, we have presented the spectral properties of individual Big domain of Lig proteins, and showed that an individual domain binds Ca(2+). Here we demonstrate that apart from Ca(2+)-binding properties, the spectral properties (such as doublet Trp fluorescence) shown by an individual domain are almost retained in the protein with many such domains (which could easily be called a multimer of an individual tandem repeat). Presence of Asp and Asn in a stretch of sequence in all tandem repeats points towards the possibility of their involvement in Ca(2+)-binding. PMID- 21980573 TI - Mitochondria associated membranes (MAMs) as critical hubs for apoptosis. AB - Apoptosis is a process of major biomedical interest, since its deregulation is involved in the pathogenesis of a broad variety of disorders (neoplasia, autoimmune disorders, viral and neurodegenerative diseases, to name a few). It is now firmly established that variations in cellular calcium (Ca(2+)) concentration are pivotal in the control of a variety of cellular functions. Strong evidence has been accumulated supporting a central role of Ca(2+) in the regulation of cell death. In particular, in the context of the biochemical mechanisms of apoptosis, increasing evidence support a role for endoplasmic reticulum (ER) mitochondria Ca(2+) cross talk as a crucial regulator of several pathways of apoptosis. Recent data highlight as also the promyelocytic leukemia protein (PML), by modulating the ER machinery at the contact sites between ER and mitochondria (the mitochondria associated membranes, MAMs), regulates cell survival through the ER-cytosol/mitochondria Ca(2+) signaling. PMID- 21980574 TI - In vivo cell biology using Gal4-mediated multicolor subcellular labeling in zebrafish. AB - The behavior of a cell is determined by the interplay of its subcellular components. Thus, being able to simultaneously visualize several organelles inside cells within the natural context of a living organism could greatly enhance our understanding of developmental processes. We have established a Gal4 based system for the simultaneous and cell type specific expression of multiple subcellular labels in transparent zebrafish embryos. This system offers the opportunity to follow intracellular developmental processes in a live vertebrate organism using confocal fluorescence time-lapse microscopy. Using this approach we recently showed that the centrosome neither persistently leads migration nor determines the site of axonogenesis in migrating neurons in the zebrafish cerebellum in vivo. Here we present additional in vivo findings about the centrosomal and microtubule dynamics of neuroepithelial cells during mitotic cleavages at early neural tube stages. PMID- 21980575 TI - Regulation of apical membrane enrichment and retention of plasma membrane Ca ATPase splice variants by the PDZ-domain protein NHERF2. AB - The localization of plasma membrane calcium ATPase (PMCA) isoforms in specified membrane compartments is crucial for their function in local Ca(2+) handling. PMCA2w/b is present in the apical membrane whereas alternative splice variants PMCA2x/b and 2z/b reside in the basolateral membrane in polarized epithelial cells. Here we found that the apical scaffolding protein NHERF2 greatly enhances the apical concentration of PMCA2w/b by tethering the pump to the underlying actin cytoskeleton. The interaction requires the C-terminal PDZ binding sequence in PMCA2b and results in increased membrane retention and decreased lateral mobility of the pump. In contrast, PMCA2x/b remains exclusively basolateral even when NHERF2 is overexpressed. Our results suggest that the alternatively spliced intracellular loop in PMCA2 imposes dominant membrane targeting information. NHERF2-mediated recruitment may be an effective means for polarized cells to regulate the abundance of PMCA2w/b in the apical membrane to meet an increased demand for local Ca(2+) extrusion. PMID- 21980576 TI - Actin switches in phagocytosis. AB - Exposure of phagocytes to non-spherical particles has provided evidence for multiple actions of the actin system in force generation. For the uptake of long cylindrical particles, a "motile actin clamp" mechanism is proposed. When a phagocyte is engaged with an hour-glass-shaped particle, it exerts contractile activity alternatively at the far end of the particle or at its concave region. Phagocytes can switch within seconds between these different strategies of taking up a particle. This response switching is based on reprogramming the pattern of actin polymerization and depolymerization. The choice between different strategies of interaction with a particle increases the probability of engulfing the entire particle or at least a portion of it. Finally, a switch to actin disassembly enables a phagocyte to release a particle that turns out to be too big to be enclosed. PMID- 21980577 TI - Changes in single K channel behavior induced by a lipid phase transition. AB - Membrane protein activity is affected by the properties of the lipid bilayer hosting them. These properties are established by both the lipid composition and the thermodynamic state of the bilayer. In the latter case, any parameter that can alter the state of the bilayer is indirectly able to affect the activity of membrane proteins. In a recent study, we have demonstrated that the activity of the KcsA ion channel is strongly related to the thermodynamic state of the lipid bilayer. In particular, when the lipid bilayer is in its main phase transition region, the conductivity of KcsA is increased and all its characteristic times change according to the characteristic times of the lipid bilayer. We propose here that the lipid bilayer can affect the distribution among many conformational substates of the open channel, affecting the corresponding channel conductivity. PMID- 21980578 TI - Towards a two-body neuroscience. AB - Recent work from our interdisciplinary research group has revealed the emergence of inter-brain synchronization across multiple frequency bands during social interaction.1 Our findings result from the close collaboration between experts who study neural dynamics and developmental psychology. The initial aim of the collaboration was to combine knowledge from these two fields in order to move from a classical one-brain neuroscience towards a novel two-body approach. A new technique called hyperscanning has made it possible to study the neural activity of two individuals simultaneously. However, this advanced methodology was not sufficient in itself. What remained to be found was a way to promote real-time reciprocal social interaction between two individuals during brain recording and analyze the neural and behavioral phenomenon from an inter-individual perspective. Approaches used in infancy research to study nonverbal communication and coordination, between a mother and her child for example, have so far been poorly applied to neuroimaging experiments. We thus adapted an ecological two body experiment inspired by the use of spontaneous imitation in preverbal infants. Numerous methodological and theoretical problems had to be overcome, ranging from the choice of a common time-unit for behavioral and brain recordings to the creation of algorithms for data processing between distant brain regions in different brains. This article will discuss the underlying issues and perspectives involved in elucidating the pathway from individual to social theories of cognition. PMID- 21980579 TI - Quantitative models of signal transduction networks: How detailed should they be? AB - Receptor-mediated signal transduction networks, comprised of multiple biochemical pathways, control cell responses and are therefore central to normal and aberrant physiological processes. An appreciation for the inherent complexities of these networks has matured in recent years, to the point where it is now apparent that experimental measurements will need to be combined with computational modeling and analysis to best interpret and predict how individual mechanisms (proteinprotein interactions, enzymatic reactions, etc.,) are integrated at the network level. To progress along these lines, there is a major barrier to overcome: although a deep mechanistic understanding of signal transduction has been achieved, data sets of a suitably quantitative nature are still lacking. Based on our efforts to systematically acquire and analyze such measurements, we contend that the level of detail in models of signaling networks ought to be limited by the availability of quantitative data, rather than by the much greater availability of qualitative information about signaling interactions. Although this approach is sensible from a data-driven modeling perspective, it is controversial because it gives the false impression that molecular-level details are being ignored. PMID- 21980580 TI - Presenilin-2 modulation of ER-mitochondria interactions: FAD mutations, mechanisms and pathological consequences. AB - Presenilin (PS) mutations are the main cause of Familial Alzheimer's Disease (FAD) and have been demonstrated to cause an imbalance of intracellular Ca(2+) homeostasis. Though PS1 and 2 are generally considered to behave similarly in terms of their effects on Ca(2+) handling, we have recently described a novel function, which is unique to PS2, i.e., the modulation of ER-mitochondria juxtaposition. Accordingly, PS2, but not PS1, affects the Ca(2+) cross-talk between these organelles, a key feature in determining cell fate. In particular, PS2 overexpression, and more drastically that of FAD-linked PS2 mutants, strongly increases the interaction between ER and mitochondria, thus facilitating mitochondrial Ca(2+) uptake. The likely mechanisms behind this phenomenon and its potential effects in cell physiology and pathology are discussed. PMID- 21980581 TI - Non-random sharing of Plantae genes. AB - The power of eukaryote genomics relies strongly on taxon sampling. This point was underlined in a recent analysis of red algal genome evolution in which we tested the Plantae hypothesis that posits the monophyly of red, green (including plants) and glaucophyte algae. The inclusion of novel genome data from two mesophilic red algae enabled us to robustly demonstrate the sisterhood of red and green algae in the tree of life. Perhaps more exciting was the finding that >1,800 putative genes in the unicellular red alga Porphyridium cruentum showed evidence of gene sharing with diverse lineages of eukaryotes and prokaryotes. Here we assessed the correlation between the putative functions of these shared genes and their susceptibility to transfer. It turns out that genes involved in complex interactive networks such as biological regulation and transcription/translation are less susceptible to endosymbiotic or horizontal gene transfer, when compared to genes with metabolic and transporter functions. PMID- 21980582 TI - Listeria infection modulates mitochondrial dynamics. AB - Mitochondria are highly dynamic organelles that are central to several cellular processes, the most prominent being energy production. Several reports have shown that pathogens target mitochondria in various ways to interfere with apoptosis, but to our knowledge only one study has specifically addressed the effects of infection on mitochondrial dynamics. We focused on this aspect during infection with the intracellular pathogen L. monocytogenes and could recently show that this bacterium profoundly alters mitochondrial dynamics, causing transient fragmentation of the mitochondrial network. This mitochondrial fragmentation occurs early during infection and is specific to pathogenic L. monocytogenes, as it is not observed with other intracellular pathogens. The relevance of mitochondrial dynamics for L. monocytogenes infection is highlighted by the finding that siRNA-mediated inhibition of mitochondrial fusion or fission decreases or increases the efficiency of L. monocytogenes infection, respectively. The main bacterial factor responsible for mitochondrial network disruption was identified as the secreted pore-forming toxin listeriolysin O, which also appeared to impair mitochondrial function. Our work suggests that in order to establish an efficient infection, L. monocytogenes interferes with cellular physiology at early timepoints by transient disruption of mitochondrial dynamics and function. PMID- 21980584 TI - Parastomal Hernia-the Achilles Heel of a Permanent Colostomy. PMID- 21980583 TI - Structures of reverse transcriptase pre- and post-excision complexes shed new light on HIV-1 AZT resistance. AB - HIV-1 resistance to 3'-azido-2',3'-deoxythymidine (AZT, zidovudine) results from mutations in reverse transcriptase that increase the ability of the enzyme to excise AZT-monophosphate after it has been incorporated. Crystal structures of complexes of wild type and mutant reverse transcriptase with double-stranded DNA with or without the excision product, AZT adenosine dinucleoside tetraphosphate (AZTppppA), have recently been reported. The excision-enhancing mutations dramatically change the way the enzyme interacts with the excision product. PMID- 21980585 TI - Condition for good quality of life after surgery for slow transit constipation. PMID- 21980586 TI - Management of colorectal trauma. AB - Although the treatment strategy for colorectal trauma has advanced during the last part of the twentieth century and the result has improved, compared to other injuries, problems, such as high septic complication rates and mortality rates, still exist, so standard management for colorectal trauma is still a controversial issue. For that reason, we designed this article to address current recommendations for management of colorectal injuries based on a review of literature. According to the reviewed data, although sufficient evidence exists for primary repair being the treatment of choice in most cases of nondestructive colon injuries, many surgeons are still concerned about anastomotic leakage or failure, and prefer to perform a diverting colostomy. Recently, some reports have shown that primary repair or resection and anastomosis, is better than a diverting colostomy even in cases of destructive colon injuries, but it has not fully established as the standard treatment. The same guideline as that for colonic injury is applied in cases of intraperitoneal rectal injuries, and, diversion, primary repair, and presacral drainage are regarded as the standards for the management of extraperitoneal rectal injuries. However, some reports state that primary repair without a diverting colostomy has benefit in the treatment of extraperitoneal rectal injury, and presacral drainage is still controversial. In conclusion, ideally an individual management strategy would be developed for each patient suffering from colorectal injury. To do this, an evidence-based treatment plan should be carefully developed. PMID- 21980587 TI - Surgical treatment of a parastomal hernia. AB - PURPOSE: Parastomal hernia is a major complication of an intestinal stoma. This study was performed to compare the results of various operative methods to treat parastomal hernias. METHODS: Results of surgical treatment for parastomal hernias (postoperative recurrence, complications and postoperative hospital stays) were surveyed in 39 patients over an 11-year period. The patients enrolled in this study underwent surgery by a single surgeon to exclude surgeon bias. RESULTS: Seventeen patients were male, and twenty-two patients were female. The mean age was 65.9 years (range, 36 to 86 years). The stomas were 35 sigmoid-end colostomies (90%), 2 loop-colostomies (5%), and 2 double-barrel-colostomies. Over half of the hernias developed within two years after initial formation. Stoma relocation was performed in 8 patients, suture repair in 14 patients and mesh repair in 17 patients. Seven patients had recurrence of the hernia, and ten patients suffered from complications. Postoperative complications and recurrence were more frequent in stoma relocation than in suture repair and mesh repair. Emergency operations were performed in four patients (10.3%) with higher incidence of complications but not with increased risk of recurrence. Excluding emergency operations, complications of relocations were not higher than those of mesh repairs. Postoperative hospital stays were shortest in mesh repair patients. CONCLUSION: In this study, mesh repair showed low recurrence and a low complication rate with shorter hospital stay than relocation methods, though these differences were not statistically significant. Further studies, including randomized trials, are necessary if more reliable data on the surgical treatment of parastomal hernias are to be obtained. PMID- 21980588 TI - Surgical outcomes after total colectomy with ileorectal anastomosis in patients with medically intractable slow transit constipation. AB - PURPOSE: The aim of this study was to evaluate outcomes of a total colectomy with ileorectal anastomosis in patients with slow transit constipation. METHODS: A retrospective review of 37 consecutive patients with slow transit constipation who underwent a total colectomy between 1994 and 2008 was undertaken. Preoperative and postoperative Wexner's constipation scores were collected and used to evaluate the outcomes after surgical treatment. Also patients' postoperative satisfaction scores were collected using a 4-point scale. RESULTS: The 37 patients consisted of 31 women and 6 men, with a median age of 41 years (range, 17 to 71 years). Pre- and post-operative Wexner's scores were collected from 33 patients (89.1%), and the mean preoperative Wexner's score was 19.3 (range, 11 to 24), which decreased to an average post-operative score of 2.3 (range, 0 to 8). Neither intraoperative complications nor postoperative mortalities were noted. Five patients (13.5%) had early postoperative complications, and the most common complication was postoperative ileus (10.8%). Seven patients (18.9%) had late postoperative complications, and postoperative ileus (10.8%) was also the most common. Twenty seven of 33 patients were satisfied with their surgical outcome (81.8%). CONCLUSION: A total colectomy with ileorectal anastomosis might be an effective surgical procedure with acceptable morbidity to treat medically intractable slow transit constipation. PMID- 21980589 TI - Is conservative treatment with antibiotics the correct strategy for management of right colonic diverticulitis?: a prospective study. AB - PURPOSE: The goals of this study were to identify whether conservative treatment with antibiotics in right colonic diverticulitis (RCD) patients, our empirical method used until now, is adequate and to determine how the natural history of RCD is affected by conservative treatment. METHODS: This study was designed as a case-control study. Group I was comprised of 12 patients who were managed conservatively, and clinical data were retrospectively collected. In group II, a total of 49 patients, diagnosed by using diagnostic criteria for RCD and managed conservatively, were prospectively included. RESULTS: The period of fasting was 2.7 days, and the hospital stay was 4.6 days in all patients. The intravenous and the oral antibiotic periods were 3.8 days and 9.8 days, respectively. There were no statistically significant differences in treatment results between the two groups except the duration of fasting and the hospitalization, and there were no complications under conservative treatment. Eight patients (13.1%) had recurrent diverticulitis during the follow-up period. The recurrence risk showed no significant difference between the groups. The RCD-free period after management was 60.1 months, and patients with recurrent RCD were treated by conservative treatment or laparoscopic surgery. CONCLUSION: Conservative treatment with antibiotics is the optimal treatment of choice for RCD and shows no increase in complications. PMID- 21980590 TI - Value and interpretation of resection margin after a colonoscopic polypectomy for malignant polyps. AB - PURPOSE: This study was designed to compare the clinicopathologic findings of an endoscopic polypectomy for malignant polyps with subsequent surgery and to evaluate the appropriateness of the pathologic finding criterion of the resection margin as an indicator for surgery in cases of malignant colorectal polyps. METHODS: We examined the clinicopathologic characteristics, complications and prognoses among the patients who underwent a colonoscopic polypectomy in both our hospitals and at other hospitals from April 2003 and April 2010. These patients were divided into two groups, the group (non-operation group) that only underwent a polypectomy (n = 37) and the group (operation group) that underwent a polypectomy with subsequent surgery (n = 33). RESULTS: There were no differences between two groups in the ratios of the number of men to the number of women, the ages or the comorbidities. In terms of endoscopic findings, we found no differences between the two groups in the locations of the polyps, the sizes of the polyps, or the presence of stalks. However, ulceration of polyps was higher in the non-operation group (51.5% vs. 21.6%; P = 0.009), as was the case with submucosal invasion (75.8% vs. 16.2%; P < 0.005). When an endoscopic polypectomy was performed, incomplete resection margins and specimens with margins involved occurred more frequently in the operation group (93.9% vs. 51.4%; P < 0.005), but no residual tumor was detected in 31 of 33 (93.9%) patients in that group. One pathologist reviewed the specimens of 54 patients (operation group, 19; non operation group, 36). Six of the 19 polyps (31.6%) in the operation group and fifteen of the 36 polyps (41.7%) in the non-operation group had a margin without cancer cells. CONCLUSION: We may accept the criterion of a safe margin, including a coagulation zone. A multidisciplinary approach has to be developed by surgeons, endoscopists and pathologists based on a discussion of the risk factors for the patient before making a decision on the treatment treatment. PMID- 21980591 TI - Clinical applications of radio-frequency ablation in liver metastasis of colorectal cancer. AB - PURPOSE: The aim of this study is to evaluate long-term survival and prognostic factors for radio-frequency ablation (RFA) in colorectal liver metastases. METHODS: We retrospectively reviewed 35 colorectal liver metastases patients who underwent RFA between 2004 and 2008. We analyzed survival after RFA and prognostic factors for survival. RESULTS: Of the 35 patients, 23 patients were male and 12 were female. Their mean age was 62.40 +/- 12.52 years. Mean overall survival was 38.8 +/- 4.6 months, and mean progression free survival was 19.9 +/- 3.4 months. Three- and 5-year overall survival rates were 42.7 +/- 0.1% and 26.0 +/- 0.1%, respectively. Three- and 5-year progression-free survival rates were 19.6 +/- 0.1% and 4.9 +/- 0.04%, respectively. Overall survival and progression free survival were significantly improved in male and in patients with carcinoembryonic antigen (CEA) <= 100 ng/mL, carbohydrate antigen (CA) 19-9 <= 100 ng/mL, absence of extrahepatic disease, and a unilobar hepatic lesion. In addition, progression-free survival was improved in patients with a solitary hepatic lesion. On the multivariate analysis, significant survival factors were the absence of extrahepatic disease and the presence of a unilobar hepatic lesion. CONCLUSION: RFA for colorectal liver metastases is an effective treatment option in male patients and in patients with CEA or CA19-9 <= 100, absence of extrahepatic disease, a solitary hepatic lesion, and a unilobar hepatic lesion. PMID- 21980592 TI - A case of successful colonoscopic treatment of colonic obstruction caused by phytobezoar. AB - A phytobezoar is the most common type of bezoar, which is a gastrointestinal mass composed of vegetable. A persimmon is a common cause of a phytobezoar. The majority of bezoars are found in the stomach, with the small intestine being the next most commonly involved site. The colon is a rare site for a bezoar. Recently, we experienced a colonic bezoar that caused colonic obstruction in a 66 year-old female patient who took persimmons regularly. The patient came to the hospital because of abdominal pain and distension. To differentiate a tumor or other problems that can cause intestinal obstruction, we performed an abdominal computed tomography scan and found an ovoid intraluminal mass with a mottled gas pattern in the distal descending colon. A large impacted bezoar was seen in the sigmoid colon, which was completely obstructed, and it was successfully removed by using colonoscopy. PMID- 21980593 TI - A case of endoscopic resection of a colonic semipedunculated leiomyoma. AB - During colonoscopic examination, epithelial lesions, such as adenomatous polyps, are frequently encountered, unlike subepithelial lesions, such as leiomyomas, which are uncommon. A colonic leiomyoma is a rare tumor, originating either from the mucularis mucosa or from the proper muscle, and accounts for only 3% of all gastrointestinal leiomyomas. Colonic leiomyomas are usually benign and asymptomatic. However, they can sometimes cause symptoms, ie, abdominal pain, intestinal obstruction, hemorrhage, and perforation. The traditional management option for a colonic leiomyoma is surgical resection. Recently, with the development of endoscopy devices and techniques, the endoscopic resection has been considered as an alternative treatment option. We experienced a patient with a leiomyoma that was diagnosed during colonoscopy. The leiomyoma was resected endoscopically without complication. We report this case with a review of the literature. PMID- 21980595 TI - IgG-detection devices for the Tus-Ter-lock immuno-PCR diagnostic platform. AB - The number of new Immuno-PCR technologies and applications is steadily growing as a result of a general need for more sensitive immunoassays for early detection of diseases. Although Immuno-PCR has been demonstrated to be superior to its immunoassay counterpart, it is still regarded as a challenging technology due to various problems arising from its increased detection power, such as high background noise as well as substantial batch-to-batch reproducibility issues. Current efforts have intensified to produce homogeneous universal protein-DNA conjugates to simplify this technology and render it more robust. We have recently developed a new quantitative Immuno-PCR (qIPCR) technology using the Tus Ter-lock (TT-lock) interaction to produce homogeneous protein-DNA conjugates that can detect very small numbers of disease-related antibodies. We now report the further development of the TT-lock Immuno-PCR platform for the quasi universal quantitative detection of antigens and mammalian IgG. For this, Tus was fused to various IgG-binding proteins--i.e. protein G, protein L and their LG chimera--and self-assembled to the TT-lock-T template. These detection devices were then evaluated and applied in various direct and indirect Immuno-PCR formats. The direct TT-lock qIPCR could detect goat anti-GFP IgG at concentrations as low as 0.3 pM and total human IgG in serum samples with great sensitivity. Further indirect TT-lock qIPCR systems were developed that could detect 1 pM of GFP and 10 pM of measles nucleoprotein. In all cases, the superiority of the TT-lock Immuno-PCR was demonstrated in terms of sensitivity over an analogous Protein G Peroxidase ELISA. PMID- 21980594 TI - Bio-inspired supramolecular self-assembly towards soft nanomaterials. AB - Supramolecular self-assembly has proven to be a reliable approach towards versatile nanomaterials based on multiple weak intermolecular forces. In this review, the development of bio-inspired supramolecular self-assembly into soft materials and their applications are summarized. Molecular systems used in bio inspired "bottom-up self-assembly" involve small organic molecules, peptides or proteins, nucleic acids, and viruses. Self-assembled soft nanomaterials have been exploited in various applications such as inorganic nanomaterial synthesis, drug or gene delivery, tissue engineering, and so on. PMID- 21980596 TI - Wavelength-orthogonal photolysis of neurotransmitters in vitro. AB - Irradiation of a mixture of 4-methoxyphenacyl-caged (S)-glutamate and 4,5 dimethoxy-2-nitrobenzyl-caged gamma-amino butyric acid (GABA) on neurons, at ~260 nm, evokes selective photorelease of (S)-glutamate (Glu) whereas photolysis at 405 nm causes selective photorelease of GABA. PMID- 21980597 TI - Aging gracefully?: patient safety advocates call for ongoing skills assessments for older physicians. PMID- 21980598 TI - Reaping the whirlwind: emergency physician recounts his fateful brush with deadly twister in Joplin, MO. PMID- 21980599 TI - High-content aptamer-based proteomics. PMID- 21980600 TI - Ventricular fibrillation in ST-segment elevation myocardial infarction. PMID- 21980601 TI - Dynamic downsloping ST-segment depression in the left precordial leads: acute myocardial ischemia or ...? PMID- 21980602 TI - Demodex folliculitis. PMID- 21980603 TI - Getting your cat to the veterinarian. PMID- 21980604 TI - Bruce D. Sidell (20 March 1948-8 February 2011). PMID- 21980605 TI - My journey with Bruce Sidell. PMID- 21980606 TI - Acute and preventive pharmacologic treatment of cluster headache. PMID- 21980608 TI - Simplification of grading papillary urothelial neoplasia using a reduced set of diagnostic features. AB - OBJECTIVE: To determine whether a reduced set of the histopathologic features used in internationally accepted classifications is capable of accurately grading papillary urothelial neoplasms (PUN). STUDY DESIGN: All surgical specimens from urinary bladders received during a 2-year period were reexamined by an expert uropathologist for assessing the accuracy of original nonexpert PUN grading and staging. Thirteen histopathologic features entailing 32 attributes were evaluated with regard to prediction of expert grade. Patients were followed for 35-59 months (mean, 47). RESULTS: A total of 88 PUN specimens could be analyzed completely including follow-up specimens. Agreement between original and expert grade was 71% for low-grade and 87% for high-grade PUN, with overall kappa = 0.53. The histomorphologic features most predictive of expert grade were architectural disorder, variability of nuclear enlargement, and absence of umbrella cells. Neither individual histomorphologic attributes nor their combinations were as predictive of expert pathologist grade as original diagnoses. CONCLUSION: Improvements in PUN grading and prognostication are not likely to be accomplished by only reducing the number of histomorphologic features currently recommended by the World Health Organization and International Society of Urological Pathology. PMID- 21980607 TI - Differential expression of estrogen and progesterone receptors in endometrial polyps and adjacent endometrium in postmenopausal women. AB - OBJECTIVE: To evaluate the immunoexpression of estrogen receptor (ER) and progesterone receptor (PR) in gland and stromal cells of endometrial polyps in postmenopausal women. STUDY DESIGN: Thirty postmenopausal patients underwent operative hysteroscopies because of benign endometrial polyps. The polyps were identified and subsequently completely removed. A section of normal-appearing endometrium adjacent to the polyp base was also obtained for the control group. The presence of ER and PR was investigated in the gland and stromal cells in the polyps and adjacent endometrium using immunohistochemistry. The slides were evaluated by semiquantitative analysis. RESULTS: Endometrium and endometrial polyps showed a significantly higher proportion of positive cells in the glands than in the stroma for both ER (p < 0.000 and p < 0.000, respectively) and PR (p = 0.002 and p = 0.002, respectively). Polyps showed a significantly higher proportion of positive cells in glands and stroma than in the endometrium, concerning ER (p < 0.000 and p = 0.001, respectively) and also for PR (p = 0.021 and p = 0.008, respectively). CONCLUSION: Our data suggest that steroid receptors present a crucial role in the physiopathology of the endometrial polyps in postmenopausal women. PMID- 21980609 TI - Diagnosis of intraurothelial neoplasia. Interobserver variation and the value of individual histopathologic attributes. AB - OBJECTIVE: To determine interobserver variation in histopathologic diagnosis of carcinoma in situ (CIS) and dysplasia (collectively intraurothelial neoplasia [IUN]) of the bladder and identify histomorphologic features important for diagnosis. STUDY DESIGN: A total of 272 consecutive bladder tissue samples were re-evaluated blindly by two general pathologists and one uropathologist for IUN. Discrepancies were resolved jointly. Fifteen histopathologic attributes were evaluated for prediction of diagnosis. Followup revealed recurrence and progression rates for each diagnostic category. RESULTS: Thirty-six percent of specimens contained no evaluable flat mucosa; 51% percent of specimens from papillary urothelial neoplasia (PUN) cases showed CIS. General pathologists detected 56-69% of CIS and 8-42% of dysplasia. Histopathologic features most predictive for CIS were nuclear size, variation in nuclear shape, loss of maturation, loss of polarity, and architectural disorder. None of these individually or in combination exceeded general pathologists' diagnostic accuracy. IUN was not predictive of recurrence or progress. CONCLUSION: Using material mostly consisting of flat mucosa gratuitously provided in PUN resection specimens, IUN carries no prognostic value. General histopathologists detect IUN poorly to moderately, and the five most discriminatory histomorphologic features are insufficient for diagnosis. Interobserver agreement for dysplasia is dismal. Absent flat mucosa in PUN resections predicts recurrence. PMID- 21980610 TI - Fractal and lacunar dimension of the chorionic villi of molar pregnancy. AB - OBJECTIVE: To explore the role of fractal geometry to differentiate molar pregnancies from normal chorionic villi. STUDY DESIGN: We selected at random 15 cases each of first-trimester normal chorionic villi, complete hydatidiform mole, and partial mole. Fractal dimension (FD) and lacunar dimension (LD) were measured in each case using the box counting method. FD and LD were compared in the three groups. RESULTS: Mean FD was highest in the normal chorionic villi (1.7520), followed by partial mole (1.6696) and complete mole (1.6438). Analysis of variance (ANOVA) showed a significant difference of FD in normal villi vs. complete (p < 0.001) and partial mole (p < 0.001). There was no significant difference of FD between complete and the partial mole. The mean LD of normal, partial, and complete molar villi was 0.5067 +/- 0.6944, 0.6063 +/- 0.09670, and 0.5551 +/- 0.11277, respectively. The mean LD was significantly increased between partial mole and normal villi (ANOVA, p < 0.006). However, there was no significant difference of LD between the partial and complete mole and between complete mole and normal villi. CONCLUSION: The measurement of FD and LD along with the histopathology of the lesions may be helpful to distinguish molar and nonmolar villi. PMID- 21980611 TI - Computer-aided diagnosis of melanocytic skin tumors by use of confocal laser scanning microscopy images. AB - OBJECTIVE: To check the applicability of machine learning algorithms for the computer-aided diagnosis of confocal laser scanning microscopy (CLSM) views of skin lesions. STUDY DESIGN: Features, based on spectral properties of the wavelet transform, are very suitable for the automatic analysis because architectural structures at different scales play an important role in diagnosis of CLSM views. The images are discriminated by several machine learning algorithms, based on Bayes-, tree-, rule-, function (numeric)-, and lazy-classifiers. RESULTS: The function and lazy classifiers delivered best classification results. However, these algorithms deliver no information about the inference mechanism leading to the classification. The tree classifiers provided better results than the rule classifiers. To obtain more insight into the inference process, and to compare it with the diagnostic guidelines of the dermopathologists, we combined the advantages of tree, numerical, and rule classifiers and choose the classification and regression trees (CART) algorithm, which automatically generates accurate inferring rules. The classification results were relocated to the images by use of the inferring rules as diagnostic aid. CONCLUSION: The discriminated elements of the skin lesions images show tissue with features in good accordance with typical diagnostic CLSM features. PMID- 21980612 TI - Morphometric analysis of DNA ploidy and nuclear cell cycle regulators in Ewing's sarcoma/primitive neuroectodermal tumor. AB - OBJECTIVE: To study the morphometry of DNA ploidy as a prognostic factor, compare qualitative and quantitative methods using immunohistochemical markers, and evaluate the utility of morphometry in the differential diagnosis of Ewing's sarcoma family of tumor (ESFT) subtypes and small round cell tumors (SRCTs) of bone. STUDY DESIGN: A total of 111 genetically confirmed ESFTs and 19 SRCTs were evaluated for DNA content and immunohistochemistry for p53, p16, and Ki-67 using morphometric analysis. Qualitative evaluation was performed using light microscopy. RESULTS: Of the ESFT cases, 81% were aneuploid. Overall, no statistical differences were observed regarding the nuclear area or roundness between ESFT and SRCT and between ESFT subtypes. p53 and p16 revealed high concordance between qualitative and quantitative methods and a lower agreement using Ki-67. Nuclear roundness showed prognostic significance in the univariate analysis for proportional risk survival but no independent prognostically significant variable was obtained after multivariate analysis. CONCLUSION: DNA content, nuclear area, or roundness cannot distinguish between ESFT and other SRCT. Morphometric analysis cannot discriminate between ESFT histologic subtypes. Quantitative measurements of IHC parameters are more precise than conventional measurements, particularly in discrepant cases (--vs. +, ++ vs. +++). DNA ploidy is not a prognostic factor in ESFT. PMID- 21980614 TI - Penile cancer: different histopathologic types with a critical clinical approach. PMID- 21980613 TI - Role of microsatellite instability in young patients with laryngeal carcinoma. AB - OBJECTIVE: To determine whether early development of carcinoma in young patients could be explained by an alternative pathway such as microsatellite instability or whether it follows the classical tumor suppressor pathway characterized by loss of heterozygosity. STUDY DESIGN: Microsatellite instability, loss of heterozygosity, and multiple mismatch repair, p16, p53, and p63 protein expression were analyzed in a series of 18 young patients with laryngeal cancer. RESULTS: Only 2 of the 18 cases showed low microsatellite instability, whereas 9 of 17 presented loss of heterozygosity in at least one of the markers tested. All cases retained multiple mismatch repair protein expression. The p53, p16, and p63 expression profiles were consistent with the classical tumor suppressor pathway. CONCLUSION: Laryngeal carcinoma in young patients develops through the classical tumor suppressor pathway. PMID- 21980615 TI - Recognition of linear stress fibers based on Hough transform. AB - OBJECTIVE: To present an algorithm based on Hough transform for recognition and extraction of linear stress fibers formed on exposure to lysophosphatidic acid (LPA). STUDY DESIGN: A ridge set of head points with lower shoulders is calculated, followed by a thinning process shrinking long, narrow regions to regions of single pixel thickness, then converted into a rectangular map whose value is the number of regional points in the path of a straight line at the angle and intercept determined by two coordinates. The location of the maximum in the map is sought, and the corresponding line with an unlimited length is constructed from the paired coordinates. We removed the line before repeating the process for the next longest straight line, continuing until all lines with reasonable lengths are extracted. RESULTS: Application of the algorithm to the stress fiber images of DOV13 cells stained with Texas red-phalloidin on LPA and AG1478 demonstrates close matches between stress fibers in the original images and linear lines. CONCLUSION: An algorithm for recognition of linear stress fibers formed on exposure to LPA is described and applications to stress fiber images using DOV13 cells with Texas red-phalloidin staining are demonstrated. PMID- 21980616 TI - A preliminary study of the potential of tree classifiers in triage of high-grade squamous intraepithelial lesions. AB - OBJECTIVE: To investigate the potential value of tree classifiers for the triage of high-grade squamous intraepithelial lesions. STUDY DESIGN: The dataset comprised 808 histologically confirmed cases having a complete range of the cytologic sample assessments--liquid-based cytology, reflex human papillomavirus (HPV) DNA test, E6/E7 HPV mRNA test, and p16 immunocytochemical examinations. Data include 488 histologically negative (cervical intraepithelial neoplasia [CIN] 1 and below) or clinically negative cases and 320 with histologic diagnosis of CIN 2 or worse. Cytologic diagnosis was made according to the criteria of the Bethesda System. Cases were classified in two groups according to histology: those with CIN 2 or worse and those with CIN 1 and below. Fifty percent were randomly selected as a training set and the remaining were as a test set. RESULTS: Application of tree classifier on the test set gave correct classification of 66.9% for CIN 2 and above cases and 97.3% for CIN 1 and below, producing overall accuracy of 91.5%, outperforming cytologic diagnosis alone. CONCLUSION: Application of tree classifiers, based on standard cytologic diagnosis and expression of studied biomarkers, produces improved classification results for cervical precancerous lesions and cancer diagnosis and PMID- 21980617 TI - Computerized morphometry as an aid in distinguishing recurrent versus nonrecurrent meningiomas. AB - OBJECTIVE: To use novel digital and morphometric methods to identify variables able to better predict the recurrence of intracranial meningiomas. STUDY DESIGN: Histologic images from 30 previously diagnosed meningioma tumors that recurred over 10 years of follow-up were consecutively selected from the Rambam Pathology Archives. Images were captured and morphometrically analyzed. Novel algorithms of digital pattern recognition using Fourier transformation and fractal and nuclear texture analyses were applied to evaluate the overall growth pattern complexity of the tumors, as well as the chromatin texture of individual tumor nuclei. The extracted parameters were then correlated with patient prognosis. RESULTS: Kaplan Meier analyses revealed statistically significant associations between tumor morphometric parameters and recurrence times. Tumors with less nuclear orientation, more nuclear density, higher fractal dimension, and less regular chromatin textures tended to recur faster than those with a higher degree of nuclear order, less pattern complexity, lower density, and more homogeneous chromatin nuclear textures (p < 0.01). CONCLUSION: To our knowledge, these digital morphometric methods were used for the first time to accurately predict tumor recurrence in patients with intracranial meningiomas. The use of these methods may bring additional valuable information to the clinician regarding the optimal management of these patients. PMID- 21980618 TI - Fractal pattern of canine trichoblastoma. AB - OBJECTIVE: To assess by fractal analysis the specific architecture, growth pattern, and tissue distribution that characterize subtypes of canine trichoblastoma, a benign tumor derived from or reduplicating the primitive hair germ of embryonic follicular development. STUDY DESIGN: Tumor masks and outlines obtained from immunohistologic images by gray threshold segmentation of epithelial components were analyzed by fractal and conventional morphometry. The fractal dimension [FD] of each investigated case was determined from the slope of the regression line describing the fractal region within a bi-asymptotic curve experimentally established. RESULTS: All tumor masks and outlines obtained by gray threshold segmentation of epithelial components showed fractal self-similar properties that were evaluated by peculiar FDs. However, only masks revealed significantly different FD values, ranging from 1.75 to 1.85, enabling the discrimination of canine trichoblastoma subtypes. CONCLUSION: The FD data suggest that an iterative morphogenetic process, involving both the air germ and associated dermal papilla, may be responsible of the peculiar tissue architecture of trichoblastoma. The present study emphasized the reliability of fractal analysis in achieving the objective characterization of canine trichoblastoma. PMID- 21980619 TI - Brownian motion curve-based textural classification and its application in cancer diagnosis. AB - OBJECTIVE: To develop an automated diagnostic methodology based on textural features of the oral mucosal epithelium to discriminate normal and oral submucous fibrosis (OSF). STUDY DESIGN: A total of 83 normal and 29 OSF images from histopathologic sections of the oral mucosa are considered. The proposed diagnostic mechanism consists of two parts: feature extraction using Brownian motion curve (BMC) and design ofa suitable classifier. The discrimination ability of the features has been substantiated by statistical tests. An error back propagation neural network (BPNN) is used to classify OSF vs. normal. RESULTS: In development of an automated oral cancer diagnostic module, BMC has played an important role in characterizing textural features of the oral images. Fisher's linear discriminant analysis yields 100% sensitivity and 85% specificity, whereas BPNN leads to 92.31% sensitivity and 100% specificity, respectively. CONCLUSION: In addition to intensity and morphology-based features, textural features are also very important, especially in histopathologic diagnosis of oral cancer. In view of this, a set of textural features are extracted using the BMC for the diagnosis of OSF. Finally, a textural classifier is designed using BPNN, which leads to a diagnostic performance with 96.43% accuracy. (Anal Quant PMID- 21980620 TI - Cytologic difference between benignity and malignancy in suspicious cases employing urine cytodiagnosis using a liquid-based method. AB - OBJECTIVE: To follow cases with atypical cells or suspicious cases on first examination by liquid-based cytology (LBC), comparing cases that became negative and those confirmed to be positive (urothelial carcinoma) with regard to the cell morphology. STUDY DESIGN: Urine cytology was performed employing LBC in 323 samples. Of 75 suspicious cases on first examination, 5 and 8 cases were identified with (positive) and without (negative) cancer on reexamination, respectively. Cell morphology was investigated in the first suspicious preparations of these cases. RESULTS: Fewer cells were present in the samples of negative cases, and atypia was generally weak. The nuclei were swollen and pale, and hyperchromatism was weak. In contrast, in positive cases, nuclear swelling, flattening, shrinkage, and pale staining were less marked compared with those in negative cases. The nuclei were hyperchromatic and irregular in many cases. Nuclear cannibalism, multinucleation, anisokaryosis, three-dimensionality, and an irregular arrangement were considered to be features strongly suggesting malignancy. CONCLUSION: The efficiency of diagnosis employing the LBC is high because of the cell collection rate. It was shown that the accuracy of diagnoses made employing the LBC method can be increased by understanding the characteristics of the cell morphology in suspicious cases. PMID- 21980621 TI - DNA damage in women with cervical neoplasia evaluated by DNA breakage detection fluorescence in situ hybridization. AB - OBJECTIVE: To evaluate the association between the progressive stages of cervical dysplasia and DNA damage. STUDY DESIGN: A hospital-based, unmatched case-control study was performed. DNA damage levels in the cervical epithelial cells of 30 women (10 with low-grade squamous intraepithelial lesions [LSIL], 10 with high grade SIL [HSILI, and 10 with no cervical lesions) were evaluated using the DNA breakage detection-fluorescence in situ hybridization (DBD-FISH) technique. DNA damage levels were measured quantitatively using image analysis after whole genomic DNA hybridization. RESULTS: LSIL patients presented a hybridization signal 20 times greater than the signal in control individuals, which reflected the basal level of DNA damage detected, and HSIL patients showed 100 times the basal control signal. The Kruskal-Wallis test showed differences between both patient groups and the control and between the patients with LSIL and HSIL. CONCLUSION: The DBD-FISH technique is easy to apply to cervical scrapings and provides prompt results. Our findings confirm that the grade of a cervical lesion correlates with the degree of genomic instability. PMID- 21980622 TI - Nuclear morphology for the detection of alterations in bronchial cells from lung cancer: an attempt to improve sensitivity and specificity. AB - OBJECTIVE: To identify which morphologic or densitometric parameters are modified in cell nuclei from bronchopulmonary cancer based on 18 parameters involving shape, intensity, chromatin, texture, and DNA content and develop a bronchopulmonary cancer screening method relying on analysis of sputum sample cell nuclei. STUDY DESIGN: A total of 25 sputum samples from controls and 22 bronchial aspiration samples from patients presenting with bronchopulmonary cancer who were professionally exposed to cancer were used. After Feulgen staining, 18 morphologic and DNA content parameters were measured on cell nuclei, via image cytom- etry. A method was developed for analyzing distribution quantiles, compared with simply interpreting mean values, to characterize morphologic modifications in cell nuclei. RESULTS: Distribution analysis of parameters enabled us to distinguish 13 of 18 parameters that demonstrated significant differences between controls and cancer cases. These parameters, used alone, enabled us to distinguish two population types, with both sensitivity and specificity > 70%. Three parameters offered 100% sensitivity and specificity. When mean values offered high sensitivity and specificity, comparable or higher sensitivity and specificity values were observed for at least one of the corresponding quantiles. CONCLUSION: Analysis of modification in morphologic parameters via distribution analysis proved promising for screening bronchopulmonary cancer from sputum. PMID- 21980623 TI - Epidermal growth factor receptor status in stages of resected non-small cell lung cancer: implications for treatment with epidermal growth factor receptor inhibitors. AB - OBJECTIVE: To verify whether epidermal growth factor receptor (EGFR) status could be considered a prognostic factor and assessment of it an effective tool for planning therapy in patients with non-small cell lung cancer (NSCLC). STUDY DESIGN: From 1996 to 2001, 439 patients underwent radical surgery for NSCLC at the Polytechnic University of the Marche Region. EGFR expression was detected as membranous and/or cytoplasmic staining of neoplastic cells with various intensity and was considered positive when > or = 1% of the tumor cells had membranous staining. RESULTS: Samples from 423 patients were available for EGFR analysis. EGFR expression and a stronger intensity of staining were associated with a trend for a worse prognosis in the analysis of all of the patients. The subgroup analysis showed no prognostic significance in stages I and II but a significantly longer survival in patients with advanced disease (stage III and particularly N2) overexpressing EGFR. CONCLUSION: The results of our study, showing a significantly longer survival in patients with advanced disease (stage III, particularly N2) overexpressing EGFR, present a new perspective, both for prognostic evaluation of patients with radically resected NSCLC and for the management of adjuvant treatment also employing targeted therapy. PMID- 21980625 TI - Multifractal spectrum of chorionic villi: a novel approach. AB - OBJECTIVE: To measure the multifractal dimension in histopathology sections of chorionic villi to study its role to distinguish between normal chorionic villi and hydatidiform mole. STUDY DESIGN: Multifractal spectrum was measured in 10 each cases of normal chorionic villi and hydatidiform mole. The values of alpha max and alpha min and their difference Delta alpha (alpha max--alpha min) were recorded in each case. The data for these groups were compared. RESULTS: The mean +/- SD of alpha max, alpha min, and Delta alpha (alpha max--alpha min) of normal chorionic villi were 2.6335 +/- 0.16109, 1.6975 +/- 0.04435, and 0.9360 +/- 0.12725, respectively. Whereas the mean +/- SD of alpha max, alpha min, and Delta of hydatidiform moles were 2.3196 +/- 0.11937, 1.6209 +/- 0.06208, and 0.7000 +/- 0.08350, respectively. The mean alpha max, alpha min, and Delta alpha of normal chorionic villi were much higher than for hydatidiform mole. Independent sample t test shows significant difference (p < 0.001) in alpha max, alpha min, and Delta alpha of normal chorionic villi and hydatidiform mole. CONCLUSION: Multifractal dimension was significantly different in normal chorionic villi and hydatidiform mole. PMID- 21980624 TI - Determination of HER2 gene status by fully automated fluorescence microscopy. AB - OBJECTIVE: To examine fluorescence in situ hybridization (FISH) in HER2 amplification in response rates to trastuzumab therapy and both taxane and anthracycline-based chemotherapy regimens. STUDY DESIGN: A total of 400 tumor sections were analyzed over an 8-month period. The sections were hybridized with probes for the HER2 gene and chromosome 17 centromere using standard FISH methods and analyzed on an automated fluorescence microscopy system. RESULTS: Reliable and valid methods for identification of the patients that will respond to treatment with trastuzumab are needed in order to achieve maximum therapy efficacy and maintain cost efficiency. FISH-based analysis is potentially an objective and reproducible approach to determination of HER2 gene status; however, manual FISH counting is a laborious task and subject to inter and intraobserver variability. CONCLUSION: The system described in this paper is a valuable tool in providing a consistent approach to the interpretation of breast tumor tissue analyzed by FISH analysis. In addition to consistency, an automated system provides a record of the images produced that can be of immediate benefit in multiple review of a difficult or equivocal case and long-term benefit in terms of providing a permanent case record. PMID- 21980626 TI - A decision support system for assisting fine needle aspiration diagnosis of thyroid malignancy. AB - OBJECTIVE: To assist diagnosis of thyroid malignancy, implementing a decision support system (DSS) using fine needle aspiration biopsy (FNAB) data. STUDY DESIGN: The set of 2,035 thyroid smears contained 1,886 smears of nonmalignancy (class 1) and 150 smears of malignancy (class 2) verified histologically. For each smear, 67 medical features were considered by the expert, forming 2,036 feature vectors, which were fed into a DSS for discriminating between malignant and nonmalignant smears. The DSS comprised a feature selection and classification module using a combination of three classifiers, the artificial neural network, the support vector machines, and the k-nearest neighbor, under the majority vote procedure. RESULTS: The overall classification accuracy of the DSS was 98.6%, marginally better than the FNAB (97.3%). The DSS had lower sensitivity (89.1%) and better specificity (99.4%) compared to the FNAB. Regarding the smears characterized as "suspicious" by FNAB, a significant improvement of overall accuracy was obtained by the proposed DSS system (84.6%) compared to the FNAB (50.0%). CONCLUSION: The proposed DSS provides significant improvement compared to FNAB regarding discrimination of smears characterized by an expert as "suspicious," reducing the number of patients undergoing surgical procedures. PMID- 21980627 TI - Clusterin as a potential marker in distinguishing cervical neoplasia. AB - OBJECTIVE: To assess the immunoexpression of clusterin (CLU) in the progression of cervical neoplasia. STUDY DESIGN: A total of 127 paraffin sections of cervical tissue consisting of normal cervical tissue, cervical intraepithelial neoplasia (CIN) lesions, cervical squamous cell carcinomas (SCCs), and adenocarcinoma of the cervix were examined by immunohistochemistry. The findings were evaluated in relation to clinicopathologic factors including grade of differentiation and lymph node involvement. RESULTS: Immunopositivity of CLU was found in the cytoplasm of dysplastic cells, SCCs, and normal epithelium of the endocervical gland. There was negative expression in adenocarcinoma. High expression of CLU was found in CIN 3 compared to CIN 1 and CIN 2. The immunoreactivity of CLU was found in 95% of SCCs. The staining was positive in the upper 2/3 layers of the dysplastic epithelium for CIN 3 and showed a cluster pattern in cervical SCCs. There was no significant correlation between CLU immunoreactivity and lymph node involvement, as well as grade of differentiation. CONCLUSION: The overexpression of CLU in various stages of cervical lesions may serve as a potential marker to distinguish cervical neoplasia with borderline morphology features. PMID- 21980628 TI - Analytical and dimensional morphometry in early diagnosis cutaneous melanoma with dermoscopic images. AB - OBJECTIVE: To give to the clinician an objective numerical assessment tool to evaluate melanomas so that a diagnosis can be reached with the assistance of computerized procedures. STUDY DESIGN: The approach adopted for differential diagnosis of melanomas and nevi considers diverse morphologic characteristics intrinsic to the lesions, that is, shape, size, and symmetry in total independence of pigmentation, and proposes that this information can be evaluated quantitatively and separately by morphometric procedures with statistically valid independent numeric variables that guarantee objectivity and, from a method point of view, consistency. RESULTS: The results show that the differential diagnosis on malignant and benign lesions is made on five variables, which all describe the fine irregularities of the contour and have a high significance in comparing melanomas to nevi. CONCLUSION: The multivariate discriminant analysis demonstrates the ability of the analytic variables to discriminate 88% of the lesions, rising to 90% if two-dimensional variables are included. PMID- 21980629 TI - Inability of immunomorphometric assessment of angiogenesis to distinguish primary versus secondary myelofibrosis. AB - OBJECTIVE: To explore the utility of bone marrow (BM) angiogenesis in differentiating primary myelofibrosis (PMF) from secondary myelofibrosis (MF). STUDY DESIGN: CD34 immunostaining was performed on BM biopsies from 21 PMFs, 23 non-PMF myeloproliferative neoplasms (MPN) with associated MF, 20 secondary MF samples, and 10 nonfibrotic controls. Microvessel density (MVD) and microvessel surface area (MSA), along with blood and BM findings were compared between the groups. RESULTS: The post-MPN MF cases included chronic myeloid leukemia-MF and polycythemia vera-MF. Etiologies of secondary MF were metastatic carcinomas, non MPN hematologic malignancies, tuberculosis, autoimmune MF, and osteopetrosis. Megakaryocytic clustering was the most frequent and intrasinusoidal hematopoiesis the most specific feature of PMF. Higher reticulin grade, collagenization, and osteomyelosclerosis were commoner in PMF. MVD and MSA were significantly increased in fibrotic marrows regardless of etiology. Although mean MVD as well as MSA were highest in PMF, extensive overlaps among groups and marked heterogeneity in the secondary MF group rendered them of limited utility in the differential diagnosis. CONCLUSION: Enhanced angiogenesis is not entirely specific for PMF. Overlaps with secondary MF limits its differential diagnostic utility. Pathogenetically, our findings suggest that enhanced angiogenesis is a secondary paraneoplastic stromal response shared by various unrelated conditions. PMID- 21980630 TI - Touch-screen technology frees nurses to spend more quality time with patients. PMID- 21980631 TI - New diagnostic criteria for Alzheimer's disease. Experts hope the guidelines will improve diagnosis and foster research. PMID- 21980632 TI - No "magic pill" for autism spectrum disorders. Although medication prescriptions are common, there is little evidence they do any good. PMID- 21980633 TI - Metabolic syndrome and mental illness. Weight gain and other unhealthy attributes increase risk of diabetes and heart disease. PMID- 21980634 TI - Delusions of infestation. Delusional parasitosis may occur on its own or as a complication of another disorder. PMID- 21980635 TI - Sedentary lifestyle can be a heart-stopper in people with depression. PMID- 21980636 TI - Antipsychotics are overprescribed for nursing home residents. PMID- 21980637 TI - Commentary. Can painkillers cap antidepressant effect? PMID- 21980639 TI - Is everywhere nowhere? nomads, nations, and the immigrant paradigm of United States history. PMID- 21980640 TI - Geographical unevenness of India's green revolution. PMID- 21980641 TI - Lee Kuan Yew: race, culture and genes. PMID- 21980643 TI - Prevalence of self-reported hypersensitive teeth among a group of Nigerian undergraduate students. AB - AIMS AND OBJECTIVES: To determine the prevalence of self reported hypersensitive teeth and relate this to the frequency and quantity of consumed carbonated drinks among a group on Nigerian dental and medical undergraduate students and the management of the condition by the students. MATERIALS AND METHODS: Self administered questionnaire was used to collect information on demography, consumption of carbonated drinks, hypersensitivity of teeth and its management from students. Students were chosen using stratified sampling method. Each level of study was taken as a stratum and students were then chosen from each stratum by systematic sampling. RESULTS: A total of 387 questionnaires were returned. Hypersensitivity of teeth was reported by 33.8% while 52.7% of them were bothered about the condition, half (50.0%) of those bothered by the condition had done nothing about it. About a third (29.7%) of the respondents, (16.3% consumed once daily and 13.4% consumed 2/more times daily) consumed carbonated drink at least once a day. A great majority (77.0%, 17.2%) either consumed 1-2 bottles (35cl/bottle) or 1-2(30cl/glass) of carbonated drinks per day respectively. Tooth sensitivity occurred more commonly among students who consumed carbonated drinks most frequently (i.e. 2 or more times a day) but there was no significant statistical association between frequency and quality of carbonated drink consumption and self-reported dentine hypersensitivity. (p>0.05) CONCLUSION: Hypersensitivity of teeth was common among the students studied but request for treatment was poor. There is need for increased public awareness on prevention and management of common dental conditions. PMID- 21980644 TI - Remembering the dead in Northop: First World War memorials in a Welsh parish. PMID- 21980645 TI - Science as cultural practice: psychiatry in the First World War and Weimar Germany. PMID- 21980646 TI - Did they jump or were they pushed? The exit of older men from the London labor market, 1929-1931. PMID- 21980647 TI - Grain storage in early modern Europe. PMID- 21980648 TI - The Sheffield boys' and girls' charity schools, 1706-1962. PMID- 21980649 TI - [Differences of optic disc appearance between normal tension and high tension glaucoma patients]. AB - INTRODUCTION: The term glaucoma is used to cover a wide range of diseases, whose main feature is optic neuropathy. According to the level of intraocular pressure (IOP), the open angle glaucoma is arbitrarily divided into high tension glaucoma (HTG) and normal tension glaucoma (NTG). OBJECTIVE: The aim of this study was to investigate the differences of optic disc cup appearance between patients with NTG and HTG. METHODS: Prospective study included 30 patients (60 eyes) with NTG and 30 patients (60 eyes) with HTG. IOP was measured by Goldmann applanation tonometry. Examination of optic disc head was performed by indirect ophthalmoscopy with Volk 90 D superfield lens through a dilated pupil to observe qualitative and quantitative parameters. Visual fields were examined in all patients with the Octopus program G1, full threshold strategy (Octopus 500 EZ, Interzeag, Switzerland). RESULTS: Vertical form of optic disc cup was present in 11 eyes with NTG (18.3%) and three eyes with HTG (5%) (p < 0.05). A disc with localized tissue loss (polar notching) on the inferior pole was observed in eight eyes with NTG (13.3%) and in one eye with HTG (1.7%) (p < 0.01). Uniformly enlarged, round cup was more frequent in patients with HTG than NTG: 93.3% and 68.3% respectively (p < 0.05). CONCLUSION: The perceived differences indicate a complex multifactorial nature of glaucoma disease and a possible existence of two pathophysiological ways of optic disc changes within the same basic disease. PMID- 21980650 TI - Analysis of risk factors in the development of retinopathy of prematurity. AB - INTRODUCTION: Retinopathy of prematurity (ROP) is a multifactorial disease that occurs most frequently in very small and very sick preterm infants, and it has been identified as the major cause of childhood blindness. OBJECTIVE: The aim of this study was to evaluate ROP incidence and risk factors associated with varying degrees of illness. METHODS: The study was conducted at the Centre for Neonatology, Paediatric Clinic of the Clinical Centre Kragujevac, Serbia, in the period from June 2006 to December 2008. Ophthalmologic screening was performed in all children with body weight lower than 2000 g or gestational age lower than 36 weeks. We analyzed eighteen postnatal and six perinatal risk factors and the group correlations for each of the risk factors. RESULTS: Out of 317 children that were screened, 56 (17.7%) developed a mild form of ROP, while 68 (21.5%) developed a severe form. Univariate analysis revealed a large number of statistically significant risk factors for the development of ROP, especially the severe form. Multivariate logistical analysis further separated two independent risk factors: small birth weight (p = 0.001) and damage of central nervous system (p = 0.01). Independent risk factors for transition from mild to severe forms of ROP were identified as: small birth weight (p = 0.05) and perinatal risk factors (p = 0.02). CONCLUSION: Small birth weight and central nervous system damage were risk factors for the development of ROP, perinatal risk factors were identified as significant for transition from mild to severe form of ROP. PMID- 21980651 TI - [Soft tissue thickness of face profile conditioning by dento-skeletal anomalies]. AB - INTRODUCTION: Orthodontic treatment of dento-skeletal anomalies is generally based on the correction of teeth and jaws relationship, while it is expected that soft facial tissue spontaneously adapts to therapeutically achieved relationship and to accompany hard tissue changes. OBJECTIVE: To establish facial soft tissue thickness conditioning by the presence of dento-skeletal anomalies. METHODS: The study was performed at the Dental Clinic of Nis, and involved the analysis of cephalometric rendgenograms in 121 patients, aged 12-18 years, with no previous orthodontical treatment. According to dento-skeletal relationship between teeth and jaws the patients were divided into four groups; class I (control group), class II of division 1, class II of division 2 and class III. The standard analysis of dento-skeletal profile was done according to Steinerand soft tissue profile according to Burstone was done in all. RESULTS: The patients of class II/1 had a significantly thinner upper lip (t = 2.650; p < 0.05) and thinner upper lip sulcus (t = 1.999; p < 0.05). The patients of class II/2 had a significantly thicker upper lip (t = 2.912; p < 0.01), while those of class III had a significantly thinner lower lip (t = 3.900; p < 0.001). CONCLUSION: The thickness of facial soft tissue considerably influences facial profile appearance in persons with a dento-skeletal anomaly. Not only do soft tissues adapt to the existing jaws relationship, but can also camouflage present anomalies. PMID- 21980652 TI - [C-reactive protein as an inflammatory marker in monitoring therapy effectiveness of acute odontogenic infections]. AB - INTRODUCTION: Clinical presentation of acute odontogenic infections may vary, while adequate evaluation of its severity is of great importance for determination of appropriate and effective therapy. OBJECTIVE: The aim of the present study was to monitor changes of C-reactive protein (CRP) levels, to correlate its values with symptoms of different acute odontogenic infections (AOI), and to monitor the effectiveness of the applied therapy. METHODS: Fifty four patients with AOI were included in the study. Eighteen patients with good drainage and normal body temperature were treated only by surgical incision without using antibiotics. Twenty-two patients with poor drainage after incision and normal body temperature were treated by surgical incision and antibiotics. Fourteen patients with elevated body temperature were treated by incision and antibiotics, irrespective of the quality of the drainage. CRP levels were measured on admission, on the 3rd and 7th day after therapy initiation. RESULTS: On admission CRP levels were higher in AOI with elevated body temperature compared to poorly and well-drained AOI. There were no differences in CRP levels between well and poorly drained AOI on admission. On the 3rd day, a decline in the CRP levels was evident in all three groups of patients, and there was no difference among the groups. On the 7th day, the CRP levels normalized in all groups. CONCLUSION: CRP levels correlate well with the severity and resolution of AOI and could be used as a reliable parameter in monitoring the effectiveness of AOI therapy. PMID- 21980653 TI - [Surgical revascularization on the beating heart in patients with low ejection fraction]. AB - INTRODUCTION: The subset of patients most likely to benefit from off-pump coronary artery bypass grafting (OPCABG) remains a controversial issue, but the technique has been proposed to decrease postoperative mortality and morbidity. Coronary artery bypass grafting (CABG) with a cardiopulmonary bypass carries a significant risk for patients with severe left ventricular (LV) dysfunction. OBJECTIVE: The objective of this study was to compare off-pump to on-pump CABG in patients with ejection fraction (EF) lower than 30%. METHODS: Prospective randomized study was carried out between June 2004 and March 2006 at the Institute for Cardiovascular Diseases of the Clinical Centre of Serbia. Sixty prospectively randomized high-risk patients divided into two groups to undergo off-pump or on-pump CABG. All recruited patients had left ventricular ejection fraction lower than 30%. RESULTS: Thirty patients averaging 59.2 years of age underwent 2.30 grafts on pump, and another 30 averaging 59.6 years of age underwent 2.03 grafts off pump. OPCABG patients exhibited a significantly less release of TnI (average 0.71 micro/L) than on-pump patients (3.00 micro/L). Inotropic requirements were less in the off-pump group. The patients undergoing OPCABG received fewer units of blood and had shorter postoperative length of stay in intensive care unit and hospital stay. There was no significant difference in hospital mortality and complication rate. CONCLUSION: The present study suggests that off-pump CABG in patients with poor LV function when compared with conventional CABG achieved similar number of grafts per patient, similar in hospital outcomes, shorter length of stay, reduced transfusion requirement, and less myocardial injury. PMID- 21980654 TI - The occurrence of new arrhythmias after catheter-ablation of accessory pathway: delayed arrhythmic side-effect of curative radiofrequency lesion? AB - INTRODUCTION: New arrhythmias (NA) may appear late after accessory pathway (AP) ablation, but their relation to curative radiofrequency (RF) lesion is unknown. OBJECTIVE: The aim of this study was to determine the prevalence and predictors for NA occurrence after AP ablation and to investigate pro-arrhythmic effect of RF. METHODS: Total of 124 patients (88 males, mean age 43 +/- 14 years) with Wolff-Parkinson-White syndrome and single AP have been followed after successful RF ablation. Post-ablation finding of arrhythmia, not recorded before the procedure, was considered a NA. The origin of NA was assessed by analysis of P wave and/or QRS-complex morphology, and, thereafter, it was compared with locations of previously ablated APs. RESULTS: Over the follow-up of 4.3 +/- 3.9 years, NA was registered in 20 patients (16%). The prevalence of specific NAs was as follows: atrioventricular (AV) block 0.8%, atrial premature beats 1.6%, atrial fibrillation 5.4%, atrial flutter 0.8%, sinus tachycardia 4.8%, ventricular premature beats (VPBs) 7.3%. Multivariate Cox-regression analysis identified (1) pre-ablation history of pathway-mediated tachyarrhythmias >10 years (HR = 3.54, p = 0.016) and (2) septal AP location (HR = 4.25, p = 0.003), as the independent predictors for NA occurrence. In four NA cases (two cases of septal VPBs, one of typical AFL and one of AV-block) presumed NA origin was identified in the vicinity of previous ablation target. CONCLUSION: NAs were found in 16% of patients after AP elimination. In few of these cases, late on-site arrhythmic effect of initially curative RF lesion might be possible. While earlier intervention could prevent NA occurrence, closer follow-up is advised after ablation of septal AP. PMID- 21980655 TI - Anthropometric and lipid parameters trends in school children: one decade of YUSAD Study. AB - INTRODUCTION: Athersclerosis is a multifactorial disease that begins in childhood. There are few reports regarding influence of risk factors on the atherosclerotic processes in early period of life and adolescence. OBJECTIVE: The aim of this study was to present and analyze risk factor trends in school children over a 10-year period that were included and followed-up by the Yugoslav Study of Atherosclerosis Precursors in School Children (YUSAD Study). METHODS: There were three examinations of selected population from 13 centres. The first examination was performed when children were 10 years of age (first group; N = 6381 participants), the second examination on the same population when they were 15 years of age (second group; N = 5017) and third when children were 19/20 years of age (third group; N = 1293). Evaluated parameters included: BMI, waist circumference (WaC) and lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride). RESULTS: A significant elevation of values (p < 0.001) of BMI, WaC and triglycerides and a significant decline (p < 0.001) of total cholesterol and LDL cholesterol in boys over 5 and 10-year period was noticed. There was a significant elevation (p < 0.001) of BMI, WaC and HDL values and a significant decline in LDL cholesterol values in girls over the 5 and 10 year period. CONCLUSION: Our results point out that girls between 10 and 19/20 years have a better lipid profile during growth. It should be stressed out that childhood and adolescence can be more beneficial in the observation of risk factor influences on pathological, genetic and clinical levels. PMID- 21980656 TI - [Breast reconstruction: correlation between different procedures, reconstruction timing and complications]. AB - INTRODUCTION: Improved psychophysical condition after breast reconstruction in women has been well documented. OBJECTIVE: To determine the most optimal technique with minimal morbidity, the authors examined their results and complications based on reconstruction timing (immediate and delayed reconstruction) and three reconstruction methods: TRAM flap, latissimus dorsi flap and reconstruction with tissue expanders and implants. METHODS: Reconstruction was performed in 60 women of mean age 51.1 years. We analyzed risk factors: age, body mass index (BMI), smoking history and radiation therapy in correlation with timing and method of reconstruction. Complications of all three methods of reconstruction were under 1.5-2-year follow-up after the reconstruction. All data were statistically analyzed. RESULTS: Only radiation had significant influence on the occurrence of complications both before and after the reconstruction, while age, smoking and BMI had no considerable influence of the development of complications. There were no statistically significant correlation between the incidence of complications, time and method of reconstruction. CONCLUSION: Any of the aforementioned breast reconstruction techniques can yield good results and a low rate of re-operations. To choose the best method, the patient needs to be as well informed as possible about the options including the risks and benefits of each method. PMID- 21980657 TI - [Incidence, risk factors and outcome of nosocomial pneumonia patients with central nervous system infections]. AB - INTRODUCTION: Pneumonia is the most frequent nosocomial infection in intensive care units. The reported frequency varies with definition, the type of hospital or intensive care units and the population of patients. The incidence ranges from 6.8-27%. OBJECTIVE: The objective of this study was to determine the frequency, risk factors and mortality of nosocomial pneumonia in intensive care patients. METHODS: We analyzed retrospectively and prospectively the collected data of 180 patients with central nervous system infections who needed to stay in the intensive care unit for more than 48 hours. This study was conducted from 2003 to 2009 at the Clinical Centre of Kragujevac. RESULTS: During the study period, 54 (30%) patients developed nosocomial pneumonia. The time to develop pneumonia was 10 +/-6 days. We found that the following risk factors for the development of nosocomial pneumonia were statistically significant: age, Glasgow Coma Scale (GCS) score < 9, mechanical ventilation, duration of mechanical ventilation, tracheostomy, presence of nasogastric tube and enteral feeding. The most commonly isolated pathogens were Klebsiella-Enterobacter spp. (33.3%), Pseudomonas aeruginosa (24.1%), Acinetobacter spp. (16.6%) and Staphylococcus aureus (25.9%). CONCLUSION: Nosocomial pneumonia is the major cause of morbidity and mortality of patients with central nervous system infections. Patients on mechanical ventilation are particularly at a high risk. The mortality rate of patients with nosocomial pneumonia was 54.4% and it was five times higher than in patients without pneumonia. PMID- 21980658 TI - Evaluation of the role of pathology in the diagnosis and differential diagnosis of pulmonary and extrapulmonary sarcoidosis. AB - INTRODUCTION; Sarcoidosis is a multisystem, granulomatous disease of unknown etiology. Sarcoid granulomas appear as immunological response to a particular but still unknown agent of the human body. OBJECTIVE: The main purpose of this study was to point out the important fact that the exact diagnosis of sarcoidosis must be estimated by clinical and pathological correlation, and team cooperation between the clinician and the pathologist. METHODS: Of 751 patients referred with the suspected diagnosis of sarcoidosis, from 1995 to 1999, 663 (431 female and 232 male) were analyzed and confirmed as having sarcoidosis stage I-III based on biopsy findings obtained by bronchoscopy, open lung biopsy, skin biopsy, liver biopsy or splenectomy. RESULTS: Diagnosis of sarcoidosis was made in 663 patients, 431 females and 232 males (ratio 1.9:1). The average age of patients varied from 16 to 67 years, with those below age 50 years being predominant (78.4%). The highest number of patients was diagnosed in stage I of lung sarcoidosis (81.7%). Sarcoidosis was the most common cause of hilar and mediastinal lymphadenopathy (72.2%). CONCLUSION: Biopsy is a necessary diagnostic procedure for pathological diagnosis of sarcoid granuloma before treatment even in patients where clinical, radiological, biochemical and immunological tests imply the diagnosis of sarcoidosis. PMID- 21980659 TI - Infantile nephropathic cystinosis. AB - INTRODUCTION: Infantile nephropathic cystinosis (INC) is a metabolic disorder due to impaired carrier-mediated transport of cystine out of cellular lysosomes. OBJECTIVE: To examine the prevalence and clinical characteristics of INC in paediatric patients with endstage renal disease (ESRD) in Serbia and give a recent statement of the disease. METHODS: ESRD database of the Centre for Paediatric Renal Replacement Therapy (RRT) in Serbia was used to identify all patients with INC who started RRT before age of 19 years during the period January 1980 - December 2008; their records concerning clinical characteristics, therapy and outcome were evaluated. RESULTS: Only three of 298 paediatric patients with ESRD had INC. The first signs of the illness were recognised during infancy. Fancony syndrome was diagnosed in the second year, but the diagnosis of cystinosis was delayed at mean 6 years. ESRD occurred in the first decade of life. All patients underwent cadaver kidney transplantation. At the end of the study period all patients were alive. A 31-year-old female patient was on maintenance chemodialysis due to graft failure after functioning for 11 years. She was growth retarded, single, unemployed, with severe signs of renal dystrophy. Two male patients (14.3 and 14.7 years old) had normal graft function, normal education, and good quality of life, although they were also severe growth retarded. CONCLUSION: The prevalence of infantile nephropathic cystinosis is low in Serbia. The diagnosis of cystinosis was delayed in all patients, although they exhibited the typical course of the disease. PMID- 21980660 TI - [Results of the modification of antireflux subserosal and submucosal implantation of the ureter into the rectosigmoid urinary reservoir after total cystectomy]. AB - INTRODUCTION: Uretero-intestinal anastomisis has a large influence on derivation quality. OBJECTIVE: The aim of the study was to present the modified serous lined extramural Abol-Enein method of implantation of low quality ureter into the sigma rectum pouch and comparison of the results with Le Duc implantation. METHODS: From 1995 to 2009, 62 dilated ureter units were implanted in the detubularized rectosigmoid urinary reservoir. In 28 units Le Duc, and in 34 Abol-Enein method was done. Urinary fistula and ileus were considered as early complications, while late complications included stenosis and reflux pyelonephritis. Frequency of urination was considered as a parameter of functionality. RESULTS: Transitory urine fistulae occurred only in the ureters implanted according to Le Duc technique in 4/28 (14.2%); the difference between the examined groups was close but still below the level of statistical significance (p = 0.07). Iieus occurred with nearly equal frequency in both groups. Stenosis on the ureteral implantation place was significantly more frequent (p = 0.04) in the Le Duc group 5/28 (21.7%) than in the Abol-Enein group 0/34 (0%). Refluxive pyelonephritis occurred in 3/34 (8.8%) of the Abol-Enein group, and in 5/28 (21.7%) of patients in the Le Duc group. Concerning the daily frequency, there was no difference between the examined groups. CONCLUSION: Uretero-intestinal anastomisis of dilated ureters through a serous-lined extramural tunnel decreases the risk of reflux in a considerable number of patients, with an acceptable level of complications. There are several advantages in comparison with Le Duc method. PMID- 21980661 TI - Surgical treatment of displaced acetabular fractures. AB - INTRODUCTION: Acetabular fractures are severe injuries, generally caused by high energy trauma, most frequently from traffic accidents or falls from heights. Fractures of the extremities, head injuries, chest, abdomen and pelvic ring injuries are most commonly associated injuries. OBJECTIVE: The purpose of this study was to evaluate the results of open reduction and internal fixation of acetabular fractures. The open anatomical reduction of the articular surface combined with a rigid internal fixation and early mobilisation have become the standard treatment of these injuries. METHODS: We conducted a retrospective analysis of 22 patients of average age 43.13 years. The patients were treated by open reduction and internal fixation at the Orthopaedic Clinic of Nis from 2005 2009. The follow-up was 12 to 60 months, with the average of 21.18 months after surgery. RESULTS: All injured patients were operated on between 4 and 11 days (5.7 days on the average). According to the classification by Judet and Letournel, 15 (68.18%) patients had an elementary acetabular fracture, whereas 7 (31.82%) patients had associated fracture. A satisfactory postoperative reduction implying less than 2 mm of displacement was achieved in 19 (86.36%) patients. The radiological status of the hip joint, determined according to Matta score, was excellent in 15 (68.18%) patients, good in 4 (18.18%) patients and moderate in 3 (13.63%) patients. According to Merle d'Aubigne Scale, the final functional results of the treatment of all operated patients were excellent in 12 (54.54%) patients, good in 7 (31.81%) patients and moderate in 3 (13.63%) patients. CONCLUSION: Surgical treatment of dislocated acetabular fractures requires an open reduction and a stable internal fixation. Excellent and good results can be expected only if anatomical reduction and stable internal fixation are achieved. PMID- 21980662 TI - [Operating cost analysis of anaesthesia: activity based costing (ABC analysis)]. AB - INTRODUCTION: Cost of anaesthesiology represent defined measures to determine a precise profile of expenditure estimation of surgical treatment, which is important regarding planning of healthcare activities, prices and budget. OBJECTIVE: In order to determine the actual value of anaestesiological services, we started with the analysis of activity based costing (ABC) analysis. METHODS: Retrospectively, in 2005 and 2006, we estimated the direct costs of anestesiological services (salaries, drugs, supplying materials and other: analyses and equipment.) of the Institute of Anaesthesia and Resuscitation of the Clinical Centre of Serbia. The group included all anesthetized patients of both sexes and all ages. We compared direct costs with direct expenditure, "each cost object (service or unit)" of the Republican Healthcare Insurance. The Summary data of the Departments of Anaesthesia documented in the database of the Clinical Centre of Serbia. Numerical data were utilized and the numerical data were estimated and analyzed by computer programs Microsoft Office Excel 2003 and SPSS for Windows. We compared using the linear model of direct costs and unit costs of anaesthesiological services from the Costs List of the Republican Healthcare Insurance. RESULTS: Direct costs showed 40% of costs were spent on salaries, (32% on drugs and supplies, and 28% on other costs, such as analyses and equipment. The correlation of the direct costs of anaestesiological services showed a linear correlation with the unit costs of the Republican Healthcare Insurance. CONCLUSION: During surgery, costs of anaesthesia would increase by 10% the surgical treatment cost of patients. Regarding the actual costs of drugs and supplies, we do not see any possibility of costs reduction. Fixed elements of direct costs provide the possibility of rationalization of resources in anaesthesia. PMID- 21980663 TI - [Successful intestinal ischemia treatment by percutaneus transluminal angioplasty of visceral arteries in a patient with abdominal angina]. AB - INTRODUCTION: Abdominal angina, also known as chronic mesenteric ischemia or intestinal angina, is a rare disease caused by intestinal flow reduction due to stenosis or occlusion of mesenteric arteries. A case of successful treatment of a patient with abdominal angina by percutaneous transuliminal angioplasty of high grade superior mesenteric artery and coeliac trunk stenosis was presented. CASE OUTLINE: A 77-year-old male patient was admitted at our Clinic for severe postprandial abdominal pains followed by frequent diarrhoeas. Extensive gastrointestinal investigations were performed and all results were normal. Multislice computerized (MSCT) arteriography was indicated which revealed ostial celiac trunk and superior mesenteric artery subocclusion. Percutaneous transluminal angioplasty of the superior mesenteric artery and coeliac trunk was done with two stents implantation. Just a few hours following the intervention, after food ingestion, there were no abdominal pains. Six months later, the patient described a significant feeling of relief after food ingestion and no arduousness at all. CONCLUSION: High-grade visceral arteries stenoses in patients with intestinal ischemia symptoms can be treated by either surgical procedures or percutaneus transluminal angioplasty. In cases when a low operative risk is anticipated, surgical treatment is recommended due to a better anatomical outcome, while percutaneus angioplasty is advised to elderly patients in whom increased operative risks can be expected. PMID- 21980664 TI - Anti-TNF treatment and miliary tuberculosis in Crohn's disease. AB - INTRODUCTION: Tumour necrosis factor alpha (TNFalpha) has a central role in the host immune response to mycobacterial infection.TNFalpha blockade may therefore result in reactivation of recent or remotely acquired infection. In reported mycobacterium tuberculosis infections, extra-pulmonary and disseminated tuberculosis (TB) was common, appeared rapidly, and if unrecognized, with fatal outcome. We present a female patient with miliary TB following treatment with infliximab for fistulizing Crohn's disease. CASE OUTLINE: Five years before admission, the patient was diagnosed with Crohn's disease, with inflammation limited to the terminal ileum and sigmoid colon and has been on azathioprine 100 mg/day for the last 10 months. Three months before admission to the hospital she developed an enterocutaneous fistula for which therapy with infliximab was started in addition to azathioprine therapy. A tuberculin skin test and a chest x ray were performed prior to the first infusion with normal findings. She presented with a 6-week history of fever, weakness, weight-loss and a 2-week dry cough. Chest x-ray and computed tomography displayed remarkable bilateral hilar and mediastinal lymphadenopathy and uniformly distributed fine nodules throughout both lung fields varying in size from 2 to 3 mm, without any signs of cavitation. Since there were clinical and morphological signs that indicated miliary TB, the treatment with antituberculous therapy was started and six weeks later all of the symptoms completely resolved and the lesions visible on x-ray diminished. CONCLUSION: The clinical use of TNF-inhibitors is associated with increased risk of developing tuberculosis. Physicians should be aware of the increased risk of reactivation of TB among patients treated with anti-TNF agents and regularly look for usual and unusual symptoms of TB. PMID- 21980665 TI - [Transfusion management of patients with alloanti-Gerbich antibodies: case report]. AB - INTRODUCTION: Transfusion management of patients who are alloimmunized against high-prevalence erythrocyte antigens is often problematic. Strategy management depends, not only on the specific clinical circumstances of the patient, but also on the acceptable time frame. In patients without clinically significant antibody incompatible transfusion it may be less harmful than delaying medical intervention. CASE OUTLINE: We report a 57-year-old female from Libya, blood group O, RhD-positive, who was treated at the Institute of Cardiovascular Diseases of Vojvodina. At the Blood Transfusion Institute of Vojvodina, during pretransfusion testing an IgG alloantibody of unknown specificity was determined. A total of 200 blood units (O, RhD-positive) were crossmatched, but positive reactions indicating that the donor units were incompatible for that specific patient. By testing the patient's family members in Tripoli, six compatible blood units were found and applied during and after surgery. Due to the deterioration of the patient's condition a rapid transfusion was required; however cross-match compatible blood was not available. After a biological cross-match to predict the clinical significance of this antibody, 12 units of erythrocytes with the lowest positive cross-match reactions, were transfused to the patient without any adverse effects. Good tolerance of the units suggested that the present antibodies were not clinically significant. Later on, a rare alloantibody directed to the high frequency Gerbich blood group antigens was identified by the Foundation Central Laboratory, Blood Transfusion Service in Bern, Switzerland. CONCLUSION: In cases of emergency patients with alloantibodies against high frequency Gerbich, when autologous or compatible alogenous transfusion is unavailable, blood with the lowest positive cross-match reaction could be transfused if the biological cross-match is negative. Formation of a national register of donors with rare blood groups and their connection with international registers is of crucial significance in the management of patients requiring antigen negative blood otherwise unavailable from routine blood banks. PMID- 21980666 TI - [Primary Burkitt's lymphoma of the stomach]. AB - INTRODUCTION: Burkitt's lymphoma belongs to the group of non-Hodgkin's lymphomas with B immunophenotypic features of lymphoma cells. It has tendency for extranodal localization primarily in the gastrointestinal tract and retroperitoneum. Primary Burkitt's lymphoma of the stomach is very rare. Stomach is most frequently involved secondarily, growing from intrabdominal tumorous mass into the stomach. CASE OUTLINE: The authors present a 30-year-old male in whom after 6 months duration of temporarily melaenas the diagnosis of Burkitt's lymphoma was established by endoscopic examination and biopsy of ulceroinfiltrative lesion on the antral part of the stomach. The patient was in clinical stage IIE. After one cycle of chemotherapy according to protocol R HyperCVAD, a subtotal distal gastrectomy and additional three cycles of the same chemotherapeutic protocol a complete remission was achieved. CONCLUSION: Burkitt's lymphoma is a highly aggressive non-Hodgkin's lymphoma often present in extranodal sites. It should be treated with systemic intensive chemotherapy and surgical removal of tumorous mass when possible. Long-term survival using the combination therapy is possible to achieve in 40-80% of patients. PMID- 21980667 TI - [Prenatal diagnosis of meconium ileus and meconium peritonitis: indications for cystic fibrosis testing]. AB - INTRODUCTION: More recently, the regions of increased abdominal echogenicity such as echogenic bowel, meconium ileus and meconium peritonitis have been associated with an increased prevalence of a variety of unfavourable outcomes including chromosomal abnormalities, cytomegalovirus infection, intestinal obstruction, anorectal malformations and cystic fibrosis. Earlier prenatal examinations of these severe autosomal recessive diseases had been suggested only to families with history of cystic fibrosis. Recently, systemic examination has been introduced by ultrasound with bowel hyperechogenicity where the fetus is the index case for genetic disease. Risk for cystic fibrosis with this ultrasonography findings ranges from 0-33%. OUTLINE OF CASES: Two patients are presented, aged 24 and 29 years, both primigravide. The first one had ultrasonography finding of meconium peritonitis revealed at the 37th week of gestation and the other meconium ileus revealed on ultrasonography at the 29th week of gestation. Both patients had prenatal testing of foetal blood obtained by cordocenthesis, both had normal kariotype and were negative for cytomegalovirus infection. Parental DNA testing for the 2nd patient showed that parents were not carriers for the 29 most frequent mutations. Both neonates had intestinal obstruction, underwent surgery and early postoperative course was normal. Hystopathological finding suggested a possibility of cystic fibrosis for the 1st patient, but parents did not want to be tested and for the 2nd one congenital bowel stenosis as a cause of intestinal obstruction. CONCLUSION: Ultrasonographic echogenic bowel is an indication for invasive procedures for foetal blood testing for chromosomal abnormalities, congenital infections and parental testing for cystic fibrosis. Only if parental heterozygosity is proven foetus should be tested. PMID- 21980668 TI - Diagnosis and treatment of deep infiltrating endometriosis with bowel involvement: a case report. AB - INTRODUCTION: Deep infiltrating endometriosis is a form of endometriosis penetrating deeply under the peritoneal surface causing pain and infertility. Assessment of the pelvis by laparoscopy and histological confirmation of the disease is considered the golden standard of diagnosis. CASE OUTLINE: We are presenting a patient diagnosed with deep infiltrating endometriosis by transvaginal ultrasound and treated with minimally invasive radical surgery including segmental resection of the bowel. CONCLUSION: Transvaginal sonography has an important role in detecting deep endometriosis of the pelvis. Fertility sparing surgery is the treatment of choice in symptomatic women wishing to retain fertility, since drugs used for endometriosis interfere with ovulation.The success of the surgery depends on the accuracy of the preoperative diagnosis. A multidisciplinary approach in managing deep endometriosis is mandatory in order to offer patients the best possible treatment using the combined skills of the colorectal and gynaecologic surgical teams. The presented case exhibits the feasibility of laparoscopic approach to severe pelvic endometriosis with bowel involvement. PMID- 21980669 TI - Silicotuberculosis and silicosis as occupational diseases: report of two cases. AB - INTRODUCTION: Silicosis, the most prevalent of the pneumoconioses, is caused by inhalation of crystalline silica particles. Silica-exposed workers are at increased risk for tuberculosis and other mycobacterium-related diseases. The risk of a patient with silicosis developing tuberculosis is higher (2.8 to 39 fold higher, depending on the severity of silicosis) than that found in healthy controls. OUTLINE OF CASES: The first patient was a 52-year-old male who was admitted in 2002 for the second time with dyspnoea, wheezing and fatigue over the last 11 years. He had worked in an iron smelting factory and was exposed to silica dust for 20 years. First hospitalization chest radiography showed bilateral pleural adhesions, diffuse lung fibrosis with signs of a specific lung process. Second hospitalization chest radiography showed bilateral massive irregular, non-homogenous calcified changes in the upper and middle parts of lungs. The patient died due to respiratory failure and chronic pulmonary heart in 2007. The main causes of his death were silicotuberculosis and chronic obstructive pulmonary disease. The second patient was a 50-year-old male who was admitted in 2005 for the second time with chest tightness, dyspnoea, wheezing and fatigue over the last 10 years. He had worked in an iron smelting factory and was exposed to silica dust for 30 years. First hospitalization chest radiography showed diffuse lung fibrosis and small nodular opacities. The patient was diagnosed with silicosis, small opacities sized level p/q, and profusion level 2/3. Second hospitalization chest radiography and CT showed diffuse lung fibrosis and small nodular opacities predominantly in the upper lobes. The patient was recognized as having an occupational disease, and received early retirement due to disability. CONCLUSION: In low-income countries, new cases of silicosis and associated lung cancer, chronic obstructive pulmonary disease and tuberculosis are likely to be seen for decades because necessary reduction of silica use will take time to be achieved. PMID- 21980670 TI - [The treatment of subtrochanteric fractures]. AB - Subtrochanteric fractures of the femur have a special place because of a significant number of complications following treatment. Powerful loading forces asymmetrically acting to this bone segment, as well as poor vascularization interfere with bone union. There are basically two current approaches in the fixation of subtrochanteric fractures; the first involves a plate with a compression screw and another one is intramedullary (IM) nail, with two options: centromedullary (standard interlocking femoral nail) and cephalomedullary femoral nail with two modifications, reconstructive and trochanteric. All IM nails may be used by open technique or closed minimal invasive method. IM nailing is favoured in view of a shorter operative time, shorter hospitalisation and complications. Indirect fracture reduction and knowledge of biology of bone fracture may result in full success without any bone graft. PMID- 21980671 TI - [Forensic psychiatry determination of mental capacity]. AB - Forensic psychiatry determination is, ordered by a court, the analysis and interpretation of medical facts with important legal implications. In that sense, psychiatrists (or neuropsychiatrists), apart from their professional expertise, must be familiar with legal, economical and social significance of medical data, so that their forensic reports are clear and useful in the context of legal procedure. This review deals with forensic psychiatry aspects of mental capacity. In the introduction of the article, the explanation of relevant concepts such as mental capacity, contractual and testamentary capacity, informed consent, undue influence and forensic determination in light of Serbian statutory law is presented. Further, the authors present basic principles of making forensic reports on mental capacity as well as contractual and testamentary capacity, and informed consent for eventual medical examination and treatment. PMID- 21980672 TI - [Contrastive analysis of Latin terms for denoting human organs and structural body parts and parts of organs in anatomy literature in English and Serbian]. AB - This paper is concerned with the analysis of the use of Latin terms in the field of human anatomy through the contrastive analysis of examples from anatomy atlases and textbooks, and research papers in the area of human anatomy in English and Serbian. The contrastive analysis of examples has highlighted a certain tendency towards the use of original Latin terms in anatomy literature in the Serbian language, while the tendency of anatomy literature in English is towards the use of English terms which most often have a Latin root. It has also been noted that Serbian literature, in addition to original Latin terms, uses a significant number of terms with a Latin root. The noted tendencies differ depending on the type of literature (anatomy atlas, textbook or research paper). A significantly greater uniformity in the use of terminology has been noted in editions in English as compared to the Serbian anatomy literature where a lack of such a uniform system is evident. Bearing in mind the ever increasing significance of the English language in the world of science, one of the conclusions of this paper is that these differences may be of practical significance for authors from Serbia looking to publish their work in English as well as for translators of medical literature. PMID- 21980673 TI - Are complications of transrectal ultrasound-guided biopsies of the prostate gland increasing? AB - Although transrectal ultrasound-guided biopsies (TRUSB) of the prostate gland are generally considered to be low-risk procedures, a study from Canada reported that there had been a significant increase in the percentage of hospital admissions following TRUSBs between 1996 and 2005 (1.0% to 4.1%). The authors speculated that the increase may be secondary to the emergence of antibiotic-resistant enteric bacteria or the result of an increasing number of cores taken with each TRUSB. In a chart review, we retrospectively evaluated complications from 2,080 consecutive TRUSBs performed by one urology group in Connecticut between January 2003 and August 2010. We identified seven patients (0.34%) who were admitted to an acute-care hospital for infectious complications and three patients (0.14%) who were admitted for bleeding. The risk of serious infections and bleeding did not significantly rise during the study period despite a significant increase in the mean number of biopsy cores taken. PMID- 21980674 TI - "A dropped call". AB - We present an interesting case of tracheobronchial foreign body aspiration. A 29 year-old healthy female, with no history of pulmonary disease, presented on multiple occasions to healthcare providers with wheezing and cough. She was repeatedly diagnosed and treated for asthma with acute exacerbations. Upon further evaluation, the patient was subsequently found to have a tracheobronchial foreign body causing her symptoms. This case report highlights a clinical approach to wheezing illnesses and reviews the diagnosis and management of tracheobronchial foreign body aspiration. PMID- 21980675 TI - Acute psychosis after paclitaxel infusion. AB - Paclitaxel (PTX) is a widely used antineoplastic agent against a variety of cancers. The common side effects are myelosuppression and peripheral neurotoxicity. There have been occasional instances of central nervous system toxicity after PTX treatment though the syndrome is not well described. We report a patient undergoing treatment for laryngeal cancer who experienced mental status changes and psychosis after each cycle of PTX and carboplatin, lasting for less than a day. In a subsequent cycle excluding PTX, these symptoms did not recur. PMID- 21980676 TI - Black esophagus in a patient with diabetic ketoacidosis. PMID- 21980677 TI - Recurrent duodenal diverticulitis after surgical resection of the diverticulum: a case report and literature review. AB - Duodenal diverticulitis has been considered a rare entity. The diagnosis with computed tomography has become a fast and noninvasive means of detection and guide to management. Cases of surgically resected duodenal diverticula reforming and reinfecting are rarer yet, often presenting with similar symptoms. Duodenal diverticulitis can present with a wide range of symptoms mimicking anything from gastritis to acute abdomen, or as in the case of our patient, as mid abdominal pain with newly developed liver abscess. According to the literature, duodenal diverticula are incidentally discovered at a rate of 5% to 10% in living adults and in up to 22% at autopsy. PMID- 21980678 TI - Atypical presentation of Creutzfeldt-Jakob disease: a rare but important cause of rapidly progressive dementia. AB - We report an atypical presentation of sporadic Creutzfeldt-Jakob disease (CJD) in a 74-year-old woman that illustrates the difficulty in diagnosing this rare, but important, cause of rapidly progressive dementia. Despite well-established criteria, this diagnosis is often missed or substantially delayed (Table 1). In this case, a precipitous cognitive decline associated with a urinary tract infection initiallysuggested delirium. Although atypical CJD was considered as a cause when symptoms persisted, a definitive diagnosis was established postmortem when the cerebrospinal fluid (CSF) prion protein 14-3-3 tested positive. Creutzfeldt-Jakob disease must be considered in the differential diagnosis of rapidly progressive dementia as Connecticut accounts for approximately three of the more than 200 cases diagnosed nationally. PMID- 21980680 TI - The 2010 North American Menopause Society position statement: Updates on screening, prevention and management of postmenopausal osteoporosis. PMID- 21980679 TI - Update on dabigatran for stroke prevention in atrial fibrillation. PMID- 21980681 TI - Medicaid patients' access to subspecialty care in Connecticut: teaching clinics questionnaire. AB - OBJECTIVE: To determine whether Medicaid patients have ready access to subspecialty care. METHODS: A survey was administered to training program directors and federal clinic chiefs to ascertain, for each medical and surgical subspecialty, whether their patients had access to care "never, rarely, sometimes, usually, or always." RESULTS: Seventeen respondents indicated that, on average, subspecialty care in Connecticut was available "never, rarely or sometimes," 36% of the time. Results of a smaller national sample, mirrored Connecticut responses. CONCLUSION: Despite government mandates, Medicaid patients have insufficient access to subspecialty care. PMID- 21980682 TI - Notes of a hospice volunteer. PMID- 21980683 TI - Training for burnout? PMID- 21980684 TI - Transitions. PMID- 21980685 TI - Organized medicine examines itself. PMID- 21980686 TI - The call for protest. PMID- 21980687 TI - A roadmap for change. PMID- 21980688 TI - Maternity matters. PMID- 21980689 TI - Have a NICE day. PMID- 21980690 TI - Here comes the sun. PMID- 21980691 TI - A topic in 10 questions: How to feed an infant with cow's milk protein allergy. PMID- 21980692 TI - Living with food allergy. AB - Food allergy is among the most common of the allergic disorders, with a prevalence of 6-8 per cent in children up to the age of three. However, many people self-diagnose, putting their children at risk of malnutrition, possibly as a result of lack of awareness by health professionals of food allergy as a potential cause of conditions such as infantile eczema, chronic diarrhoea, faltering growth and gastrooesophageal reflux. NICE (The National Institute for Health and Clinical Excellence) recently published guidelines, which they hope will help to improve the diagnosis of food allergies within the community. If food allergy or lactose intolerance is suspected, the mainstay of a diagnostic work up should comprise of a detailed allergy-focused clinical history, part of which will involve determining whether the adverse reaction is typically an immediate (IgE mediated) or more delayed-type (non-IgE mediated) allergic reaction, or whether it may be lactose intolerance; a form of non-allergic hypersensitivity. PMID- 21980693 TI - Dyspraxia series: part one. At sixes and sevens. AB - Developmental Co-ordination Disorder (DCD), also known as Dyspraxia in the UK, is a common disorder affecting motor co-ordination in children and for many continues into adulthood. This condition is formally recognised by international organisations including the World Health Organisation. DCD is distinct from other motor disorders such as cerebral palsy and stroke. The range of intellectual ability is in line with the general population. Individuals may vary in how their difficulties present. The co-ordination difficulties may affect participation and functioning of everyday life skills in education, work and employment. Children may present with difficulties in writing, typing, riding a bike, self care tasks, and recreational activities. In adulthood many of these difficulties will continue, as well as learning new skills at home and work such as planning, organisation, driving a car and DIY. PMID- 21980694 TI - Safety in numbers. PMID- 21980695 TI - Primary Care 2011. PMID- 21980696 TI - We need to partner with foundations in the battle for access to care. PMID- 21980697 TI - The best offense is a good defense: why staying on top of federal and state legislation is good for your practice. PMID- 21980698 TI - Hiring blind. PMID- 21980699 TI - What to do (and not to do) if you are sued. PMID- 21980700 TI - Solving the access to care problem will protect our profession. PMID- 21980701 TI - Cranberries: this superfood is not just for Thanksgiving. PMID- 21980702 TI - Chicago's last ADA president. PMID- 21980703 TI - Pressure, time, and soft tissue trauma. PMID- 21980704 TI - Cholera. PMID- 21980705 TI - Historical diagnosis & treatment: Sarcoma. PMID- 21980706 TI - Unusual variants of mycosis fungoides. AB - Unusual variants of mycosis fungoides (MF) differ substantially from the classical presentation, and most of them resemble other dermatologic diseases. The authors reviewed files of patients with MF who consulted our clinic between November 1995 and June 2010 to evaluate the relative frequency and clinical behavior of these variants. Among 98 patients with MF, 32 (32.65%) had unusual variants. The most common types included follicular MF (31.25%), hypopigmented MF (18.75%), poiquilodermic MF (15.6%), and erythrodermic MF (12.5%). Less common variants included unilesional MF, bullosa MF, ichthyosiform MF, granulomatous slack skin, and pigmented purpura-like MF. Progressive disease and MF-related death were most commonly associated with follicular MF, bullosa MF, and erythrodermic MF. PMID- 21980707 TI - A pentad of vancomycin reactions. AB - Vancomycin is used in the treatment of infections caused by gram-positive bacteria resistant to beta-lactam antibiotics. It is also used in the treatment ofenterococci, although this use has been limited due to resistance. The authors report the clinical and pathological presentations of 5 different vancomycin hypersensitivity reactions, including morbilliform eruption, erythroderma, acute generalized exanthematous pustulosis, linear immunoglobulin A bullous dermatosis, and toxic epidermal necrolysis. With the increased prevalence of beta-lactam resistant bacteria, reliance on vancomycin continues to increase; thus, the recognition of reactions to this drug will be helpful in caring for patients who require this medication in the future. PMID- 21980708 TI - Mobile teledermatology: As doctors and patients are increasingly mobile, technology keeps us connected. AB - With advancements in electronics and health informatics, telemedicine has emerged as a cost-effective tool capable of increasing care to remote regions, facilitating specialist consults, supporting self-management by patients, and sharing knowledge over great distances. In this review, the authors discuss existing telemedicine modalities, highlight examples of mobile systems documented in the literature to date, and emphasize the data supporting the feasibility of telecommunication technologies to deliver dermatology services and education remotely. While many studies have suggested the potential for teledermatology to increase access to care in developing countries with few dermatologists, the authors share some of the most recent developments, including the use of diagnostic decision support software. The authors encourage a thriving and open network that will enhance the ongoing research and development of innovative and useful products. This network will also connect dermatologists willing to volunteer their consultation to health care workers in remote areas lacking specialists. PMID- 21980709 TI - Noninsulin-dependent, type II diabetes mellitus-related dermatoses: part I. AB - Diabetes mellitus is a worldwide public health problem. It manifests as either insulin-dependent or noninsulin-dependent diabetes mellitus. It is associated with several dermatoses, which need to be addressed individually. Dermatoses often provide clues to the status of diabetes. The presence of dermatoses may compound the challenges confronted by the treating physician to modify the management of each patient. Several noninfective and infective dermatoses can act as a forewarning that a particular individual is likely to develop diabetes. This association is highlighted by specific entities, such as necrobiosis lipoidica and granuloma annulare and will be discussed below. PMID- 21980710 TI - The next frontier of sunscreen protection: beyond sunscreens. PMID- 21980711 TI - The three faces of cylindroma. PMID- 21980712 TI - Natroba (spinosad) 0.9% suspension topical suspension for head lice. PMID- 21980713 TI - Multiple miliary osteoma cutis of the face after initiation of alendronate therapy for osteoporosis. AB - A 62-year-old Asian woman presented with multiple small, rock-hard papular lesions on her face (Figure). She had no previous history of acne vulgaris or cutaneous malignancy. She had been diagnosed with breast cancer in 1995 and was treated with left lumpectomy followed by combination chemotherapy consisting of cyclophosphamide, 5-fluorouracil, and methotrexate. In 1995, at age 50, she also began therapy with systemic alendronate to treat osteoporosis. Within 1 year, she noticed the development of asymptomatic indurated dermal papules on her cheeks. Topical treatment with 12% lactic acid lotion did not improve her condition. Clinical examination revealed numerous 1- to 2-mm, brown dermal nodules on the malar cheeks bilaterally. Normal laboratory data included complete blood cell count, alkaline phosphatase, serum calcium, and serum phosphate. A lesional punch biopsy from the left cheek revealed lamellar bone within the dermis. Correlation of the clinical presentation, laboratory data, and pathology established the diagnosis of multiple miliary osteoma cutis of the face. PMID- 21980714 TI - Significance of Gram's stain smear, potassium hydroxide mount, culture, and microscopic pathology in the diagnosis of acrodermatitis continua of Hallopeau. AB - A 21-year-old housewife presented to the authors' clinic in 2009 with recurrent papulovesicular and pustular eruptions on the index an ring fingers of the left hand accompanied by throbbing pain that had been active for the past 10 years. The condition did not respond to topical and/or systemic treatment. There was neither a personal/family history of psoriasis nor any other systemic disease. The sk surface of the patient's left hand was marked by the presence of multiple pustules located over an erythematous background, affecting th ring and adjoining middle fingers, with crusting prominent in places along the tips (Figure 1). Gram stained smears prepared from th purulent specimen revealed Gram-positive cocci in clusters. Potassium hydroxide (KOH) examination of the pustules did not show a fungal elements. In vitro culture of the same specimen yielded growth of Staphylococcus aureus, which was found to be sensitive to almo all conventional antibiotics on aerobic culture. Sections prepared from the skin of the tip of the patient's finger showed marked epithelial hyperplasia with uniform elongation of rete ridges and supra-papillary thinning of the epidermis. There was hyperkeratosis with foci of mounds of parakeratosis. Spongiosis with neutrophilic infiltration and microabscess formation were prominent. The dermis showed perivascular lymphohistiocytic infiltrate (Figure 2A and 2B). No organism was identified on special stains. Results from hemography and liver and renal function tests were within normal limits. The diagnosis of acrodermatitis continua of Hallopeau (ACH) was made, in keeping with the findings. The patient received ceftriaxone 1.0 g and tazobactam 125 mg by slow intravenous infusion for 3 consecutive days, following which there was complete regression of the lesions. After cessation of therapy, there was complete recurrence. PMID- 21980715 TI - Refractory Hailey-Hailey disease successfully treated with sandpaper dermabrasion. AB - A 53-year-old woman presented with a 20-year history of pruritic dermatitis on the groin, axillae, inframammary folds, posterior aspect of the neck, and popliteal fossae. She was referred to our clinic by an outside facility after results from a punch biopsy diagnosed Hailey-Hailey disease (HHD). The patient had previously attempted treatment with many traditional noninvasive options with no success. Topical treatment modalities included corticosteroids, immunomodulators, antifungals, retinoids, and antibiotic preparations. Intralesional corticosteroids, as well as botulinum toxin and carbon dioxide laser, were also unsuccessful. Failed systemic treatment modalities included antibiotics, antihistamines, prednisone, azathioprine, mycophenolate mofetil, acitretin, isotretinoin, adalimumab, and etanercept. Of note, cyclosporine was successful in clearing the cutaneous involvement in our patient, but elevation ofcreatinine and exacerbated hypertension precluded continued use. The decision was made to treat the patient by dermabrasion with sandpaper. The patient was prepped in a sterile fashion, and a field block with 1% lidocaine with epinephrine was performed. This was followed by abrasion down to the superficial dermis with 3M Sandblaster fine sandpaper (3M, St. Paul, MN) and hyfrecation between rounds ofdermabrasion. The treated areas were then covered with petrolatum and sterile gauze, and antibiotics and pain medication were prescribed. This treatment was initially performed on the patient's posterior aspect of the neck and later to the bilateral popliteal fossae and axillae. Three months post-treatment, desirable functional and cosmetic results of the treated areas had been achieved (Figure 1 and Figure 2). While no recurrence of clinically active HHD has been seen in the dermabraded areas of the neck and popliteal fossae, the patient continues to have active disease in the axillae despite sandpaper dermabrasion. To quantify our results, we performed two biopsies in the dermabraded sites of the popliteal fossae as healing occurred: a shave biopsy from an obviously active area, and a punch biopsy from a peripheral inactive border. The biopsy from the active area showed diffuse epidermal acantholysis similar to that seen in untreated HHD, while the healing periphery showed only scattered acantholytic areas and a sparse perivascular infiltrate-a marked improvement from the untreated areas. PMID- 21980716 TI - Logos: what's in a symbol? PMID- 21980718 TI - Malignant acanthosis nigricans in rectal adenocarcinoma. AB - A case of generalized malignant acanthosis nigricans is reported. The patient was asymptomatic of any gastrointestinal complaints and investigations revealed the presence of adenocarcinoma of the rectum. The association between paraneoplastic acanthosis nigricans and internal malignancy is well established and the most common association is with adenocarcinoma of gastrointestinal origin. PMID- 21980717 TI - Medical-legal partnerships: lawyers and physicians working together to improve health outcomes. PMID- 21980719 TI - Dental sleep medicine--is it right for you? PMID- 21980720 TI - Glutaraldehyde/HEMA in clinical dentistry. PMID- 21980721 TI - Fixed prosthodontics: time to change the status quo? AB - The majority of indirect restorations placed in the United States are currently made by conventional procedures in 2 or more appointments, including standard impressions using VPS or polyether, use of dental laboratory technicians to make the restorations, and conventional cementation procedures. The likelihood of rapid change to digital impressions and/or in-office milling is not predicted. However, some dentists have changed to making digital impressions and sending the information to specific dental laboratories to have the crowns fabricated. In general, they are satisfied with the concept and the restorations thus produced. It is anticipated that digital impressions will slowly continue to grow until the concept eventually dominates the market. In-office milling of restorations by CEREC or E4D is now a reliable clinical process in spite of an arduous and long period of development. It is anticipated that this concept will continue to grow. At this time, any of the 3 concepts discussed in this article--conventional procedures, digital impressions sent to a laboratory, or digital impressions followed by in-office milling--are acceptable depending on the preferences of practitioners. PMID- 21980722 TI - Light up your practice. PMID- 21980723 TI - Intention of prevention: Understanding the practical and predictable options. PMID- 21980724 TI - Increasing efficiency and accuracy with digital technology. PMID- 21980725 TI - Rejuvenation via biologically-guided technology. PMID- 21980726 TI - Ultrasonics in endodontics: luxury or necessity? PMID- 21980727 TI - Customizing your career and restorations. PMID- 21980728 TI - Stabilizing and securing an RPD with a single implant. PMID- 21980729 TI - Technology makes a complicated implant restoration simple. PMID- 21980730 TI - A conservative treatment option for tetracycline staining. PMID- 21980731 TI - The diode laser--The diode laser in second stage implant reovery. PMID- 21980732 TI - Liver metastases. AB - Liver metastases are a very common site of distant metastases. Detection and accurate characterization of liver metastases is of importance to guide therapy. A variety of imaging modalities such as US (including contrast agents), MDCT, MRI with liver -specific contrast agents and PET/CT are available for this purpose. This review presents imaging techniques and summarizes the current knowledge, how the different imaging modalities should be used. PMID- 21980733 TI - Imaging of bladder cancer: update on current approaches for diagnosis. AB - Imaging plays a mainstay role in evaluation of patients with bladder cancer, especially for diagnosis, local and distant staging and treatment follow up. In this article, we aim to review and to update conventional and functional imaging methods used in clinical management of bladder cancer. PMID- 21980734 TI - Prognostic value of vascularity index for the diagnosis of autoimmune thyroid disease. AB - AIM: To determine thyroid vascularity in healthy subjects and patients with autoimmune thyroid disease (AITD), and assess its sensitivity and specificity for the diagnosis of AITD. METHODS: High-sensitivity color flow Doppler sonography (HSCFDS) was used to estimate the thyroid intraparenchymal vascularity in 31 euthyroid patients with Hashimoto's thyroiditis (HD), 33 hypothyroid patients with HD, 13 hyperthyroid patients with Graves' disease, and in 34 healthy controls. Images obtained from the ultrasound unit were further processed with a widespread, available imaging analysis program and the predictive value of the maximum vascularity index (VI) was used for further statistical analysis. RESULTS: Compared to healthy controls, patients with AITD had higher mean VI of both the right and the left thyroid lobe (TL) (P < 0.001). The sensitivity of left TL VI values greater than 5.57% (the best cut-off value of the Receiver Operating Characteristics-ROC curve) for the diagnosis of AITD was 80.8% and the specificity was 85.3%. Right TL VI values greater than 14.75% had 84.6% sensitivity and 86.2% specificity for the differential diagnosis among patients with HT or GD. CONCLUSIONS: Measurement of right and left TL vascularity index using HSCFDS is a high specific tool, particularly where there is a high clinical suspicion of an autoimmune process. PMID- 21980735 TI - CT-guided percutaneous drainage of lung abscesses: review of 40 cases. AB - PURPOSE: To evaluate the safety and effectiveness of CT-guided percutaneous drainage of lung abscesses considering success rate versus complications. METHODS: This retrospective study was carried out at Computed Tomography and Interventional Radiology Department of Sotiria Hospital, Athens, Greece, from 1/1/2007 to 1/1/2010. Forty patients with lung abscesses in which antibiotic therapy failed and were managed with CT-guided percutaneous drainage were included in the study. Catheter placement was carried out using Trocar technique in the majority of the cases. RESULTS: Lung abscess completely resolved with no residual cavity in thirty three patients. Seven patients had residual cavity and surgery was performed. Thus, the success rate of radiological drainage of the lung abscesses (33/40) was 83%. Five (13%) patients developed pneumothorax. Three developed moderate pneumothorax and chest-tube needed to be inserted and two patients developed mild pneumothorax which was managed with aspiration. These patients were kept under observation and followed-up by chest X-rays. No other complications and no mortality occurred during the procedure for all the forty patients. CONCLUSION: CT-guided percutaneous catheter drainage is a useful and safe procedure for the treatment of patients with lung abscesses who do not respond to medical therapy and should be considered a valuable alternative to open surgery. PMID- 21980736 TI - Late presentation of ureteral injury following laparoscopic colorectal surgery. AB - Iatrogenic ureteral injury is an uncommon but dangerous complication of abdominal and pelvic surgery. When recognized and promptly treated, most ureteral lesions heal without sequelae. Instead, undetected injuries may last for a prolonged period of time since symptoms and signs are usually subtle and nonspecific, even if evolution may be life threatening. In doubtful cases the diagnostic role of modern multiphase helical computed tomography is crucial. We describe the late presentation in the Emergency Department of a case of double left ureteral injury after abdominal surgery, and illustrate the appearance of the lesions at computerized tomography. PMID- 21980737 TI - Testicular sarcoidosis. AB - We describe a very unusual form of sarcoidosis of the testis, mimicking malignancy at initial presentation. Genitourinary sarcoidosis is rare and this case report emphasizes the importance of meticulous analysis of the patient's clinical history combined with imaging findings and specific pathological criteria to diagnose this granulomatous disorder. PMID- 21980738 TI - Imaging in index finger radial collateral ligament injury: attention to detail really pays.... AB - Radial collateral ligament of the index finger is a rare ligament to rupture. X ray is generally normal, except for subtle findings of soft tissue swelling and occasionally a small fracture. With continuous advances in imaging, ultrasound and high quality MRI allow clear depiction of small structures including joint capsule and collateral ligaments of even the small joints. This helps in definitive diagnosis and determines the extent of injury, which may affect the treatment options and final outcome. We report a rare case of index finger metacarpo-phalangeal joint radial collateral ligament tear. The subtle X-ray abnormality was chased on ultrasound and the diagnosis was proposed on ultrasound and later confirmed on MRI. We also discuss the imaging findings of this rare entity. PMID- 21980739 TI - Abnormal left single pulmonary vein: case report of an anecdotal variant. AB - We describe here a patient with a very rare ectopic unilateral single pulmonary vein, with normal distal drainage into the left atrium, and thus a non pathologic finding to be distinguished from clinically significant abnormalities. PMID- 21980740 TI - Unusual clinical manifestation of lymphangiomatosis. AB - A 6-year- old boy presented with disseminated intravascular coagulation and was diagnosed with lymphangiomatosis. Disseminated intravascular coagulation develops in a minority of cases. Bone lesions were present on his left shoulder. The authors discuss the diagnostic findings and medical management. PMID- 21980741 TI - Stage III xanthogranulomatous pyelonephritis treated with antibiotherapy and percutaneous drainage. AB - Xanthogranulomatous pyelonephritis (XPN) is a rare inflammatory condition usually secondary to chronic obstruction caused by nephrolithiasis and resulting in infection and irreversible destruction of the renal parenchyma. Its standard therapy consists of total or partial nephrectomy. A case of stage III xanthogranulomatous pyelonephritis treated with antibiotherapy and percutaneous drainage is presented in this paper. PMID- 21980742 TI - Conservative surgery for left-sided isolated tubal torsion in pregnancy. AB - We report a case of severe lower abdominal pain in a pregnant woman at 35 weeks and 4 days of gestation. Early diagnosis of an isolated left-sided tubal torsion was established by ultrasound and emergency magnetic resonance imaging (MRI). Subsequent detorsion surgery was able to prevent the need for salpingectomy. The role of emergency imaging and conservative surgery in isolated tubal torsion is discussed. PMID- 21980743 TI - Takotsubo cardiomyopathy or apical ballooning: a case report and a short literature study. AB - Takotsubo cardiomyopathy is an important differential diagnosis in patients with an acute coronary syndrome. This syndrome is typically characterized by a reversible contractile dysfunction of the left ventricular myocardium without any obstructive etiological coronary disease. This is not a rare entity in acute settings and a better knowledge of the syndrome could result in a heightened alertness and a higher detection. We present a case of takotsubo showing the importance of cardiac MRI in the differential diagnosis and reviewed the present literature concerning this syndrome and the usefulness of MRI in the detection. PMID- 21980744 TI - Solitary osteochondroma: spontaneous regression. PMID- 21980745 TI - Multicentric carpal-tarsal osteolysis. PMID- 21980746 TI - Ossification of the ligamentum flavum in the cervical spine. PMID- 21980747 TI - Mondor's disease of the breast. PMID- 21980748 TI - Reversible splenic ischemia in inflammatory bowel disease. PMID- 21980749 TI - Hyperostotic meningioma mimicking skull osteoma. PMID- 21980750 TI - Fast progressive memory loss in a 63-year-old man. PMID- 21980751 TI - A male infant presenting with acute urinary retention. PMID- 21980752 TI - Oblique meniscomeniscal ligament: a potential pitfall in the diagnosis of knee injury. PMID- 21980753 TI - Supreme Court embraces minimal relief for California prisoners with mental disabilities and other serious health care needs. PMID- 21980754 TI - Tudor turmoil at Westminster. PMID- 21980755 TI - Whither the House of Lords. PMID- 21980756 TI - "The difficult art of giving". PMID- 21980757 TI - Clinical negligence today. PMID- 21980758 TI - AIDS--Africa and US. PMID- 21980759 TI - Surgery--a new dark age? PMID- 21980760 TI - Seeing and feeling headaches. PMID- 21980761 TI - Comparative medicine--how bright the cross lights. PMID- 21980762 TI - Barnet, beard and bath: Edmund Harman, barber to the "king's most royal person". PMID- 21980763 TI - Are patients changing in a way which renders doctors increasingly alienated from them? PMID- 21980764 TI - Prevalence of Neospora caninum and Toxoplasma gondii antibodies in sera from camels (Camelus dromedarius) in Riyadh Province, Saudi Arabia. AB - From April to December 2010, blood samples were collected from 412 healthy camels in Riyadh province, Saudi Arabia and used to evaluate serological screening for Neospora caninum and Toxoplasma gondii infection by an indirect fluorescent antibody test (IFAT). Of the 412 camels, antibodies to N. caninum were found in sixteen in titers of 1:20 and in seven in titers of 1:40 using whole N. caninum tachyzoites as IFAT slide (VMRD Inc., Pullman, WA 99163, USA). Antibodies to T. gondii were found in nineteen camels in titers 1:20 and in eight camels in titers 1:40 using whole T. gondii tachyzoites as IFAT slide. PMID- 21980765 TI - A controlled study of nitazoxanide (NTZ) 3 years after treatment of hepatitis C genotype 4. AB - This study is an extension of an earlier, randomized; placebo-controlled that showed the efficacy of nitazoxanide (NTZ) 500 mg tablets twice daily for 6 months in treating HCV genotype 4. Access was available to 13/32 patients of the original study with chronic HCV during more than 3 years after the study was finished. One patient (with portal hypertension and oesophageal varices "O.V") was among 3 with SVR out of 9 of the NTZ treated patients suggesting that NTZ could successfully be used even in patients with O.V. SVR remain so up to the end of the follow-up period compared to none of the other 4 patients who received placebo. A fourth patient of NTZ group achieved virological response at the end of follow-up although she firstly showed RVR and then viral breakthrough. Most of the remaining patients of the NTZ group who did not achieve SVR showed variable partial response. No serious adverse events were reported in both groups during treatment and thereafter. PMID- 21980766 TI - Clinical varieties of Toxocariasis canis in Children's Hospital, Mansoura University: is it an underestimated problem? AB - Human toxocariasis is a worldwide parasitic disease. Children are more frequently infected because of the closer contact with contaminated soil and relatively frequent geophagia. Toxocariasis in children has variable modes of presentation but clinical diagnosis is difficult. Various clinical phenotypes of toxocariasis in symptomatic children attending Children's Hospital Mansoura University were studied. A total of 480 children were included in the study with mean age 7.24 +/ 4.22 years, 61.9% were boys and 200 age-sex-matched healthy controls. Patients were examined clinically, and the anti-Toxocara antibodies in the blood of children were performed by ELISA using T. canis larval excretory-secretory products as antigen. Eosinophils level in peripheral blood was measured. Sero positive cases were 12 % of patients and only 3.5% of controls. Statistical analysis showed a significant association between infection and male sex (P <0.001). Sero-positive children were older than the sero-negative (P <0.001). Eosinophilia was detected in 86.2% of sero-positive children. Sero-positivity and degree of eosinophilia were more frequently detected among patients with allergy (bronchial asthma and urticaria). Degree of eosinophilia was found to be positively correlated to the optical density (OD) ELISA of anti-Toxocara IgG. PMID- 21980767 TI - Breeding habitats characterization of Anopheles mosquito (Diptera: Culicidae) in Najran Province, Saudi Arabia. AB - An ecological study on mosquito larval breeding habitats was conducted in Najran Region, Saudi Arabia during 2005-2006 to study the breeding habitats determinants for Anopheles mosquito in two ecological types (cities and villages). The increased rate of developmental activities promotes man-made mosquito breeding habitats, which regulate Anopheles mosquito abundance or absence. The linear regression analysis revealed that An. gambiae s.l. abundance or absence is regulated by the presence of natural water habitats, which has the highest rate (79%) in villages. Other ecological, biological and physiochemical predictors for Anopheles mosquito larvae abundance or absence in the two ecological types were discussed. PMID- 21980768 TI - Threat of dengue fever and dengue haemorrhagic fever to Egypt from travelers. AB - Dengue (DF) and dengue hemorrhagic fevers (DHF) are present in urban and suburban areas in the Americas, South-East Asia, the Eastern Mediterranean and the Western Pacific, but dengue fever is present mainly in the rural areas of Africa. Several factors have combined to produce epidemiological conditions in developing countries in the tropics and subtropics that favour viral transmission by the main mosquito vector, Aedes aegypti as the rapid population growth, rural-urban migration, inadequate basic urban infrastructure (eg. the unreliable water supply leading householders to store water in containers close to homes) and the increase in volume of solid waste, such as discarded plastic containers and other abandoned items which provide larval habitats in urban areas. Geographical expansion of the mosquito has been aided by the international commercial trade particularly in used car-tyres which easily accumulate rainwater. Increased air travel and the breakdown of vector control measures have also contributed greatly to the global burden of dengue and DH fevers. The presence of Ae. aegypti and endemicity of DF and DHF in the neighbor- ing regional countries must be in mind of the Public Health Authorities. PMID- 21980769 TI - Hepatitis C and B virus in schistosomiasis patients on oral or parenteral treatment. AB - Egypt leads the world in hepatitis C infection cases. Schistosomiasis and hepatitis C virus (HCV) co-infection is common in Egypt. Hepatitis B (HBsAg) is also encountered. Potassium antimony tartarate was used for schistosomiasis in endemic areas all over the world for more than 50 years, intravenously and was prohibited since late of the last century when the oral drugs were developed. Some authors postulated that schistosomiasis might contribute to persistence of HCV via biological factors. This study compared the prevalence of HCV and HBV among schistosomiasis patients in endemic areas given parenteral or oral route antischistosomiasis. A total of 102 manual workers patients were selected from different areas in Cairo and Gharbia Governorates. They were 82 males and 20 females; their age was ranged between 16-60 years (40 +/- 12). Sheets were filled out on each patient including name, age, sex, history of haematurea or bloody diarrhea, parasitic infection, intravenous injections, blood transfusion, dental care, shaving, previous treatment, and anti-schistosomiasis. They were divided into GI: 50 patients treated IV since 20-30 years ago with ages (49.4 +/- 7.4) and GII: 52 patients treated orally up to 8 years ago with ages (2.2 +/- 7.7). They were subjected to IHAT antischistosomal antibodies, circulating schistosome antigens in urine, HBsAg and HCVAb, the latter was confirmed by PCR for positivity, and Alanin transeferese (ALT). In GI, 42/50 (84%) had HCV compared to 4/52(7.7%) in GII, with statistical significant. HBsAg was detected in a patient. HCV patients showed abnormal liver function. 3/52 received oral treatment showed elevation of liver function (5.8%). 10% (10/50) of GI and 34.6% (18/52) of GII were schistosomal antigen in urine positive. PMID- 21980770 TI - Field studies on dominant rodents and the efficacy of certain insecticides to their fleas in Dakahlia Governorate, Egypt. AB - A preliminary survey of domestic rodent and the efficacy of bendiocarb, diazinon and pirimiphos-methyl insecticides to their fleas were carried out in Dakahlia Governorates (Aga, Meet-Ghamr, El-Senbellawen, Temi El-Amded, Beni-Abed, Dekernes, Nabarow, Talkha, Menia El-Nasr and El-Kordy). Rodent index (number of rodent/trap) and percentage frequency of drodent species were recorded from October 2010 to May 2011. The main rodent species found were the Norway rat, Rattus norvegicus, the grey-bellied rat, R. rattus alexandrinus, the white bellied rat, R. r. frugivorus and the house mouse, Mus musculus. The rodent index at Beni-Abed, Nabarow, Meet-Ghamr, Dekernes and El-Kordy centers showed 0.46, 0.39, 0.34, 0.33 & 0.33, respectively, while Menia El-Nasr center showed the lowest (0.08). Aga, Talkha, El-Senbellawen, and Temi El-Amded centers showed moderate (0.25, 0.21, 0.2 & 0.16, respectively). The commonest flea species was the oriental rat flea, Xenopsylla cheopis, the mouse flea, Leptopsylla segnis, the dog flea, Ctenocephalides canis and the sticktight flea Echidnophaga gallinacea. The highest number of fleas was on R. norvegicus (Flea index=10.9) while lowest number was on Mus musculus (Flea index=0.1). X. cheopis was the highest frequency distributed for all domestic rodent species (60.9%), while, C. canis was the lowest (1.6%). The results showed that bendiocarb was effective (Lc50=0.389%) than diazinon (Lc50=1.039%) and pirimiphosmethyl (Lc50=2.056 %). PMID- 21980771 TI - Zoonotic Dicrocoeliasis dendriticum in a farmer's family at Giza Governorate, Egypt. AB - Dicrocoeliasis (Lancet liver fluke disease) is caused by Dicrocoelium dendriticum, a trematode living in bile ducts of sheep, cattle and other mammals including man. Human infection is asymptomatic or mild to moderately severe, but being sporadic or rarely reported. This paper reported zoonotic dicrocoeliasis dendriticum among a farmer's family and his domestic animals. The father and mother were successfully treated with Triclabendazole and the children and animals were successfully treated with Mirazid and Oleo-resin solution of Commiphora molmol respectively. PMID- 21980772 TI - Effect of Ramadan fasting on Muslim patients with chronic liver diseases. AB - The study evaluated the efficacy of fasting in Ramadan on the clinical, laboratory and ultrasonographic parameters of chronic liver disease patients. A total of 202 patients were selected from the departments of Tropical medicine and outpatient clinics of Al-Azhar University hospitals, Cairo, Egypt from the 26th of July till the 30th of September 2010. Patients submitted to complete clinical, laboratory, ultrasonographic and endoscopic evaluation pre, during, and post Ramadan. The fasting group was 103 (51%) and the non-fasting group was 99 (49%) patients. The non-fasting group showed significantly a good adherence to therapy (43.4%) compared to (27.2%) the fasting group (p=0.016). Dyspeptic symptoms was higher in the fasting (53.4%) compared to (38.4%) the non-fasting group (p=0.032). G.I. bleeding during Ramadan was higher in the fasting group (17.5%) compared to non-fasting (14.1%), but the bleeding due to o.v. was significantly higher in the non-fasting group (9.1%) compared to (1%) in the fasting group (p=0.004). Chronic hepatitis in the fasting group showed non significant changes pre, during and post-Ramadan regarding liver function. Fasting cirrhotic group patients child class C was developed to (13%) during and (32.6%) after Ramadan compared to (0%) before (p=0.001). PMID- 21980773 TI - Mosquitoes (Diptera: Culicidae) in relation to the risk of disease transmission in El Ismailia Governorate, Egypt. AB - Mosquito were surveyed (Nov. 2009 - March 2010) in El Ismailia Governorate. Nine species were reported: Culex pipiens, Cx. perexiguus, Cx. antennatus, Anopheles tenebrosus, An. pharoensis, An. multicolor, Ochlerotatus detritus, Oc. caspius and Culiseta longiareolata. Culex pipiens was the predominant species (ca. 87% larvae and 57% adults). For the 3 common species, Cx. pipiens, Cx. perexiguus, and Cx. antennatus the following were examined: (1) the type and characteristics (temperature and pH) of the breeding habitats and their relation to the larval density and (2) the relation of adult indoor density to the indoor and outdoor temperature and RH. The abundance of mosquito vectors in El Ismailia with its old history of vector transmitted diseases contributes to the risk of mosquito borne disease transmission in this area. This would assist in the control activities. PMID- 21980774 TI - Morphology and ultrastructure of the digenetic trematode Calicophoron microbothrium from a cow in Taif, Saudi Arabia. AB - Several digenetic trematode flukes belonging to the family Paramphistomidae were recovered from a cow slaughtered at Taif abattoir KSA. Parasites were identified as Calicophoron microbothrium (Family Paramphistomidae) .The surface tegumental structures and the anatomical details of the flukes were studied by making sagittal hand sections in the fluke and observations were made by scanning electron microscopy, which is a very useful technique in case of paramphistomes. This included the description of tegumental surface of the fluke, mouth opening and pharynx, acetabulum, genital atrium, caecum and eggs. Adult C. microbothrium is described for the first time using SEM from Saudi Arabia. PMID- 21980775 TI - Controlled mechanical ventilation with LMA Sureme versus i-gel in anesthetized adult patients. AB - The efficacy, safety and ease of insertion of LMA Supreme and the i-gel in adult cases undergoing elective surgical procedures requiring general anesthesia with controlled mechanical ventilation. This study included 60 ASA physical status I II adult patients of both sexes scheduled for elective surgical procedures under general anesthesia. Patients were randomly allocated into one of two groups; LMA S GI (n=30) and i-gel GII (n=30). A size 4 LMA Supreme and a size 4 i-gel were used with standard monitoring. Number of insertion attempts, ease of insertion, presence of gastric insufflation, laryngeal leak, leak pressure, ease of gastric tube insertion, ventilatory parameters, complications as well as hemodynamic variables was recorded. The results showed no clinically significant changes of heart rate, MAP, SpO2 or P(ET)CO2 in GI & GII. The i-gel showed higher frequency of ease of insertion (p=0.048) and gastric tube (p< 0.001). First attempt of insertion was successful in 60% of LMA-S GI and 73.3% of the i-gel GII (p=0.460) without failures in both groups. Leak pressure was significantly higher in the i gel (25.5 +/- 4.8 cm H2O) compared to the LMA-S (21.1 +/- 7.6 cm H2O) (p=0.010) while both peak and plateau pressures were significantly lower in i-gel GI (19.35 +/- 2.25 cm H2O & 17.75 +/- 2.07 cm H2O) compared to LMA-S GII (30.05 +/- 3.82 cm H2O & 28.80 +/- 3.99cm H2O) (p<0.001) respectively. There was no significant difference between both groups in the frequency of complications encountered during insertion or recovery. PMID- 21980776 TI - Clinical spectrum of fever of unknown origin among adult Egyptian patients admitted to Ain Shams University Hospitals: a hospital based study. AB - This prospective study was designed to analyze the clinical spectrum of fever of unknown origin (FUO) among adult Egyptian patients admitted to Ain Shams University Hospitals during the period from May 2009 till the end of December 2010. All Egyptian patients fulfilling the criteria of FUO admitted during this period were followed up till reaching the diagnosis. 93 patients were included in the study. They were 48 (51.6%) females and 45 (48.4%) males, their ages ranged from 15 to 65 years (34.39 +/- 13.6). Infections were the commonest cause of FUO (41.94%) followed by malignancies (30.11%). While autoimmune diseases represented 15.05% and in 12.9% of patients the diagnosis was not established. Brucellosis and infective endocarditis were the commonest infections, while hematological malignancies were the commonest oncological diseases. Systemic lupus erythematosus (SLE) was the commonest auto-immune disease. Brucellosis, infective endocarditis, hematological malignancies and SLE must be considered in the differential diagnosis of adult FUO in Egypt. PMID- 21980777 TI - Infestation status of Aega psora (Linnaeus, 1758) (Isopoda, Cymothoidae) skin parasite of the marine fish, sardine (Sardinella gibbosa) of Port Said Mediterranean Coastal Zone, Egypt. AB - An isopod parasite of family Aegidea was collected from marine fish, Sardinella gibbosa (new hosts) over 2-years period from 2007 to 2008. The fish hosts were captured in the coastal waters of Port Said, Egypt. The Cymothoa sp. & Aega sp. were only collected from skin of the new host, Sardinella gibbosa, and described on the basis of female specimens. The morphological characteristics of were discussed in details. Comparing the present specimens with the previously reported Aega sp. showed that the present material belongs to the type species of the genus: Aega psora (Linnaeus, 1758). Monthly and seasonal patterns in infestation rates [N=593, W +/- SD (range) =50.09 +/- 3.8 g]. Parasitic specificity and prevalence are given Mean prevalence, P = 24 +/- 5.5 and mean intensity, MI +/- SD =28.44 +/- 16.19 and total number of infestation were estimated 59 (10.35). PMID- 21980778 TI - Levels of helminthic infections in the quails Coturnix coturnix from Kingdom of Saudi Arabia. AB - The present study aims to clarify the difference of the intensity of parasitic infection between the domestic quails Coturnis coturnis and the migrant ones. A total of 60 domesticated and 60 migratory quails were investigated during the migration season September-November 2009 for intestinal parasites. Investigations revealed that both domestic and migrant quails were susceptible to infection with three helminth parasites; a nematode (Heterakis gallinarum), and two cestodes (Choanotaenia infundibulum and Hymenolepis sp.). The prevalence of infection in the migratory males was higher than the female ones, the opposite results was obtained for the domestic birds. The differences in the prevalence were found to be statistically significant in case of the domestic birds. Single infection showed the highest prevalence followed by the double infection and finally the triple infection. The mean intensity of infection in the female domestic and migrant C. coturnix was higher than male. PMID- 21980779 TI - Cytotoxic activity of Vitex trifolia purpurea extracts. AB - Defatted 85% crude hot aqueous methanol extract of Vitex trifolia purpurea (AME) successively extracted with, chloroform and ethyl acetate. Cytotoxicity of (AME), chloroform methanol extract (CE), ethyl acetate methanol extract (EE) and the residue obtained from methanol extract after successive extraction (RME) have been evaluated on brine shrimp (Artemia salina) and Hep-G2 cell lines as well. In brine shrimp lethality bioassay the results revealed that the (RME) is the most potent one with LC50 value 173 microg/ml while LC50 values of (AME), (CE) and (EE) was 180, 199 and 286 microg/ml, respectively. As well as the results of cytotoxic assay against Hep-G2 cell lines are in full agreement with previous results, with IC50 values 6, 10.7, 20.8 and 65.8 microg/ml for (RME), (AME), (CE) and (EE), respectively. PMID- 21980780 TI - A child with rotor syndrome and Capillaria philippinensis: case report and review of literature. AB - This paper reported Capillaria philippinensis in an Egyptian child based on clinical and laboratory diagnosis. The patient was successfullly treated with albendazole. PMID- 21980781 TI - A prospective study on parasites among expatriate workers in Al-Baha from 2009 2011, Saudi Arabia. AB - Al-Baha is an area with large influx of expatriate workers in Saudi Arabia. This study was carried out from October 2009 to January 2011 on expatriate workers (2000) to determine the prevalence of parasitosis. Urine and stool samples were collected and specifically examined. The results showed that 1079 (53.95%) were infected with one or up to ten parasitic species. Trichuris trichiura had the highest prevalence 190 (17.6%). Other helminthes were Ascaris lumbricoides 179 (16.58%), Ancylostoma duodenal 163 (15.10%), Hymenolepis nana 120 (11.12%), Taenia saginata 119 (11.02%), Strongyloides stercoralis 28 (2.59), Enterobius vermicularis 16 (1.48%), and Schistosoma mansoni 4 (0.37%). Protozoan parasites were Giardia lamblia 152 (14.09%) and Enta-moeba histolytica 108 (10.0%). Besides, Fasciola species was detected in an Egyptian worker and Dicrocelium dendriticum in one Syrian worker. Parasitic infections were higher among Indonesian people 447 (41.42%) followed by Indian 247 (22.89%), Bangladeshis 118 (10.93%), Philippines 96 (8.89%), Pakistani 94 (9.71%), Seri-Lankan 55 (5.09 %) and lastly Egyptian & Syrian 22 (2.03%) workers. The occupational imperatives, beliefs and general life style were contributing factors to the prevalence of parasites among the workers in Al-Baha. PMID- 21980782 TI - A study on Blastocystis hominis in food-handlers: diagnosis and potential pathogenicity. AB - Proper diagnosis of Blastocystis hominis in not performed routinely in medical laboratories of developing countries; consequently clinical significance of this common intestinal protozoon is liable to remain unsettled. Food-handlers are more prone to get and transmit this feco-oral infection. This work compared the sensitivity of direct diagnostic methods to detect B. hominis in stool, estimate the true prevalence among food-handlers in Sirte-Libya, to clarify the association between the parasite and gastrointestinal symptoms and the response to specific treatment. A total of 400 male food-handlers aged 18-50 year were included. Each was subjected to clinical questionnaire and 3 stool examinations by different methods. The results showed high prevalence of B. hominis in food handlers (35.5%). Short- term in vitro culture (on Boeck and Derbholav's medium) was the most sensitive method for detection of B. hominis (35.5%), followed by permanent Trichrome-stained smear (27.5%); saline-sedimentation concentrated smear (21%) and direct iodine smear (14%). Of 108 cases having B. hominis alone, 68.5% were symptomatic. Diarrhea was the most frequent symptom (75.6%), followed by abdominal pain (66.2%) and flatulence (43.2%). Fecal parasite-load was significantly higher in symptomatic cases than asymptomatic; parasite and symptoms disappeared after metronidazole treatment. So, culture should be used on routine basis to detect B. hominis which should be considered pathogenic particularly when present alone in large numbers in symptomatic patients. PMID- 21980783 TI - Causes and outcome of upper gastrointestinal bleeding in Emergency Endoscopy Unit of Ain Shams University Hospital. AB - This prospective follow-up study was designed to analyze the causes and outcome of upper gastrointestinal bleeding among patients presenting by hematemesis and/or melena to Emergency Endoscopy Unit, Ain Shams University Hospitals. One thousand patients presented by upper GIT bleeding were subjected to complete clinical evaluation, emergency upper gastrointestinal endoscopy and therapeutic interventions as indicated. Follow up was done for occurrence of re-bleeding or mortality. Variceal causes of bleeding were the most common, representing 70.1% followed by non-variceal causes (26.1%) and obscure causes (3.8%). Esophageal varices (EV) alone represented 17.8% of causes of variceal bleeding, while combined esophageal and gastric varices represented 39.5% and isolated gastric varices 12.8%. Gastric lesions were the most common causes of non variceal bleeding. Recurrence of bleeding occurred in 19.4% of variceal group in comparison to 6.1% of non variceal group, while mortality was found in 4.3% of variceal group in comparison to 1.5% of non variceal group with very highly significant difference (P <0.001). Hypertension, ascites, EV columns, EV grade IV, presence of gastric varices and associated respiratory disorder were independent factors associated with recurrence of bleeding in variceal group. In non variceal group, recurrence of bleeding was significantly related only to the presence of gastric ulcers (P=0.035). Independent factors associated with mortality in studied patients were age, associated diabetes, presence of esophageal varices and associated duodenal ulcer. PMID- 21980784 TI - Anthelmintic effect of artesunate in experimental heterophyid infection. AB - Artesunate is a water-soluble semi-synthetic drug derived from artemisinin which is extracted from leaves of the Chinese plant Artemisia annua. This successful basically-antimalarial drug has been proved to be also effective against trematodes like Schistosoma japonicum, S. mansoni, Fasciola hepatica and Clonorchis sinensis. The present work aimed to investigate the in-vivo efficacy of artesunate against heterophyids in mice, using praziquantel as a therapeutic control. Results showed that artesunate was effective in treatment of experimental heterophyidiasis as proved by a 100% reduction of intestinal adult worm count at a dose regimen of 200 mg/kg/day, given for 3 successive days. Besides, surface tegumental damage of the adult worm was observed by SEM in form of bleb formation, disruption, erosion and peeling. The proved therapeutic efficacy of artesunate together with its reported safety, favor its possible use as a new alternative therapy in human heterophyidiasis. PMID- 21980785 TI - Maternal brucellosis and human pregnancy. AB - Brucellosis is a worldwide zoonotic gram-negative bacterium of worldwide distribution. Its role in causing miscarriage in animals is well documented. Data on its role in human abortion are very few. This paper was carried out on selected women with abortion or history of abortion to clarify the role of brucellosis in human abortion. A total of 129 women were selected from Al-Zahraa University Hospital and other obstetric and gynecological hospitals in the vicinity of Greater Cairo. The patients were subjected to clinical, gynecological, and serodiagnosis (STAT and ELISA) of brucellosis. Also, routine urine (Nuclepore technique) and stool (Kato thick smear) was done as well as skin tests and ELISA for common hepatic parasites. The results showed that 59 had brucellosis, 27 had toxoplasmosis, 15 had fascioliasis and 29 had other cause(s) of abortion. Meanwhile, none had visceral leishmaniasis or schistosomiasis mansoni. the signs and symptoms of all patients were hepatosplenomegaly (31.1%), lower back abdominal pain (23.13%), lassitude, headache (each, 21.7%), lymphadenopathy (20.1%), vomiting (17.1%), loss of appetite, myalgia or diarrhea or constipation (each, 15.42 %), weight loss (14.6%), chest pain (13.9%), night sweating or dizziness (11.65%), fever or right sided abdominal pain (each, 10.7%), chills (7.71%), urticaria or monoarthralgia (each, 3.85%). These signs and symptoms were confusing for specific clinical picture of brucellosis. Brucellosis patients were successfully treated with a combination of Rifampicin 600 mg. once daily and Septrin 800 mg twice daily for 6 weeks. Cure was achieved clinically and serologically. Patients with toxoplasmosis or fascioliasis were also treated with Fasinex and Mirazid respectively. Other parasites were also treated. PMID- 21980786 TI - Assessment of Rose Bengal test in diagnosing Egyptian human brucellosis. AB - A total of 30 patients suffering from brucellosis were suspected based on history taking, clinical manifestations and positive serum tube agglutination test (at titer > or = 1/160). The followings were done for all cases; complete blood picture (differential leucocytic count) and liver function tests, serodiagnosis of Brucella (serum tube agglutination test (STAT) as well as Rose Bengal test (RBT) and PCR. The study aimed to analyze the diagnostic value of RBT as compared to STAT and PCR for human brucellosis, and to evaluate the sensitivity, specificity, accuracy, the cost and the time consuming of RBT as compared to STAT and PCR. There was a significant difference between diagnosis by RBT and both STAT > or = 1/640, & STAT > or = 1/1280. Also, there was a significant difference between PCR and both STAT > or = 1/640, and STAT > or = 1/1280. No significant difference was detected between RBT in diagnosing acute and chronic infection. STAT > or = 1/320 proved to be better than STAT at other titers and RBT in diagnosis of brucellosis. RBT proved to be suitable as screening test regarding time (faster) and cost. But, STAT > or = 1/320 from a practical and economic point of views proved to be the best one in diagnosing human brucellosis. PMID- 21980787 TI - Histochemical and ultrastructural studies on the calcareous corpuscles and eggs of Taenia taeniaeformis and Dipylidium caninum. AB - Calcareous corpuscles were noticed by several previous workers to be present in larval and adult cestodes without knowing their function. However, nothing was mentioned in the available literature about distribution of these corpuscles and their density, structure and composition in different parts of the body of different cestodes. Hence, in the present work, a comparative study of their distribution, density, histochemical and ultrastructural characters in different parts of the body was performed in Taenia taeniaeformis and Dipylidium caninum. Due to the presence of the eggs in their gravid segments, their histochemical and ultrastructural characteristics were also studied. It was found that the size, location and density of the calcareous bodies were different in different body parts of the same and the other cestode. Histochemically, the main component of these corpuscles was calcium; while other constituents as polysaccharides, lipids, protrins and mucopolysaccharides were found in their outer rim. Ultrastructurally, they were quite similar in the two studied cestodes and different stages of their development were exhibited. Histochemically, the eggs of both cestodes were similar in their contents. However, some ultrastructural differences have been demonstrated particularly in relation to the size and shape of the rods in the embryophore and the structures in between the embryophore and onchosphere. PMID- 21980788 TI - New health commission to tackle poor care issues. PMID- 21980789 TI - Continence study guides policymakers towards an integrated approach. PMID- 21980790 TI - Depression. PMID- 21980791 TI - Hospital programme for dementia-specific care. AB - This article explores the development of the Butterfly Scheme, a hospital-based, dementia-specific programme that aims to improve patient safety and wellbeing. Carer Barbara Hodkinson developed the initiative, which is an opt-in programme of care that identifies people with memory impairment, with their permission, by a butterfly symbol on their name board and notes. It also ensures carers are asked for detailed information about their relatives, such as their likes and dislikes and aspects of their daily and past life, and seeks to educate staff to interact knowledgeably, positively and appropriately using a five-point response system. Two case studies from hospitals which have introduced the scheme are presented. PMID- 21980792 TI - Simulation suit aids tailored care. AB - Nurses need to empathise with patients but it can be challenging to teach students these skills. They may struggle to make sense of situations and events unless they have experienced them. This article focuses on evaluating the effectiveness of an aged simulation suit in pre-registration nurse education to enhance knowledge and understanding of some of the changes that can occur as a consequence of ageing. PMID- 21980793 TI - Promoting a brain-healthy lifestyle. AB - The population of older adults is increasing worldwide. Old age is often associated with a continuous decline in memory and along with other forms of cognitive decline can impede the self-management abilities necessary for everyday functioning. Recent research suggests that adapting a brain-healthy lifestyle may reduce age-related cognitive decline and, in some instances, improve memory and thinking. As a health educator the gerontological nurse can help older people to navigate the information essential to improving brain health. Nurses can incorporate knowledge about brain-healthy behaviours into older adults' routines. PMID- 21980794 TI - How social care staff working in residential homes perceive their professional status. AB - AIM: The aim of the study was to explore how 'new role' and other social carers and stakeholders involved in providing enhanced health and social care for older people perceive the social care support worker's professional status. METHOD: Three different enhanced care approaches, of which two trained social care support workers to undertake new clinical support roles were studied in three residential homes: a local authority home, a voluntary sector home and a 'not for profit' independent sector home for older people. Participants were staff with national vocational qualifications at level 3 as new role carers with and without additional basic health skills awards. Other participant groups included care staff of other grades, care home managers, their parent organisation managers, and local and national stakeholders. RESULTS: Staff in all three care settings believed themselves to be professionals in the homes in which they worked but were less sure of their status in the wider health and care landscape. CONCLUSION: If the social carer workforce is to be considered a profession, it requires a professional framework in the form of a representative organisation, a code of conduct for practice and clarity as to how its new role activities interact with those of other established health professionals. PMID- 21980795 TI - Compassion research. Interview by Ruth Williams. PMID- 21980796 TI - Peach allergy. Beyond the classic 3 allergens? PMID- 21980797 TI - Allergen immunotherapy in asthma: current evidence and future requirements. AB - The role of allergen-specific immunotherapy in asthma (AIT) is still a matter of debate. Actually, many controlled clinical trials have proved efficacy and safety of AIT in asthma, and some published meta-analyses, despite some methodological weaknesses, have confirmed these findings, the most recent and convincing being a meta-analysis on injection AIT studies. For sublingual AIT evidences do exist, but SLIT meta-analyses are mostly questioned due to some biases and inconsistencies. Most of these arise from methodological problems in single studies, usually small, underpowered and carried out with mixed populations. The main need, therefore, is to perform AIT clinical studies only in patients with asthma and following standardized protocols, as recommended by international Guidelines. Studies of AIT in asthma should also focus more on the long term and preventive effects of the treatment, rather than considering only the immediate efficacy on allergic symptoms. Furthermore, specific asthma features, such as lung function, bronchial reactivity, asthma control and exacerbations, should be included among the study outcomes. PMID- 21980799 TI - Sustained clinical efficacy of sublingual immunotherapy with a high-dose grass pollen extract. AB - BACKGROUND: Sublingual immunotherapy (SLIT) with a high-dose 6-grass pollen SingleDose preparation was shown to be effective and safe in a 2-year randomized, double-blind, placebo-controlled trial. OBJECTIVE: We evaluated the effect of the third year of SLIT in comparison to the second year. METHODS: 46 grass pollen allergic patients who had received active treatment for 3 consecutive years were included in the safety set. Diary data from 39 subjects were evaluated to calculate symptom and medication scores as well as 'well days'. RESULTS: Symptoms and medication intake further decreased in the third year of SLIT during the grass pollen season in comparison to the previous years and the number of 'well days' increased accordingly. No serious adverse events occurred during the three years of SLIT. CONCLUSION: The third year of SLIT with the high-dose 6-grass pollen preparation results in sustained and even further increased clinical efficacy. PMID- 21980798 TI - Clinical relevance of non-grass pollens respiratory allergies in Italy and effects of specific sublingual immunotherapy: The Rainbow Trial, a multicentre 3 year prospective observational study. AB - OBJECTIVE: We evaluated, by means of a multicentre, prospective observational trial, the severity in term of symptoms and symptomatic drugs use and the presence of asthma in subjects with tree or cypress or olive, or ragweed or parietaria allergy and we evaluated also the efficacy of a consecutive 2-year specific sublingual immunotherapy treatment. PATIENTS AND METHOD: Consecutive patients suffering of respiratory allergies (rhinoconjunctivitis and/or mild moderate asthma) due to one of the described allergens were enrolled During the specific relevant pollen seasons for each allergens nose and eye symptoms and medication scores (SS and MS) were evaluated Global score (GS) was calculated as the sum of SS and MS. An Asthma symptom score if present, were also, calculated A total of 162 patients were enrolled in 14 Italian Allergic Clinics .Patients were treated with the relevant specific sublingual immunotherapy (SLITOne, ALK) for two consecutive pollen seasons. RESULTS: At baseline prevalence of allergies was the following: tree 18% (30 patients); ragweed 14% (23 patients); olive 7% (11 patients); cypress 7% (12 patients) and pellitory 53% (86 patients). At baseline asthma was detected in 65 patients (40%). Asthma was more common in poli sensitive subjects in comparison with mono-sensitive (51% vs. 300/o). According to allergen type, asthma was present in 47% of pellitory allergic patients, in 45% of olive allergic subjects, in 38% of ragweed allergic patients, in 26% of tree allergic patients and only in 9% of cypress allergic subjects. In pellitory, olive and ragweed allergic patients the frequency of asthma was statistically significant (P=0.0055) higher in comparison with other groups. At baseline GS mean (SD) in the whole population was 17(7). GS during the following 2 consecutive seasons with SLIT treatment decreased significantly (P=0.0001) to 9 (5) and to 7 (5), respectively (a reduction of 59% in comparison with baseline). In patients with asthma the mean clinical score decreased significantly from baseline value of 2. 7 to 0.3 at the end of the observation period No serious adverse events were reported Local side effects, mainly oral itching, were reported by 14% of patients and were mild and transient in nature. CONCLUSION: In this population pellitory, olive and ragweed allergies are associated with a more severe clinical picture in comparison with tree and cypress allergy. A two-year SLIT treatment was associated with a significant reduction in SS, MS, GS and asthma score in comparison with baseline. SLIT was also safe and well tolerated PMID- 21980800 TI - Rosaceae-associated exercise-induced anaphylaxis with positive SPT and negative IgE reactivity to Pru p 3. AB - BACKGROUND: Food-dependent-exercise-induced anaphylaxis (FDEIA) is characterized by anaphylactic symptoms after exercise following ingestion of food. We present a case of FDEIA induced by Rosacee fruits showing some diagnostic problems. MATERIAL AND METHODS: A 12 years-old boy with seasonal allergy to olive and cypressus pollens, experienced two distinct episodes of FDEIA, grade 4 and 3 of the Sampson Scale respectively, during intense exercise, about 30 minutes after eating a peach with peel or some cherries. SPT with commercial peach extract and fresh Rosacee fruits scored positive while SPT with a date palm profilin-enriched extract was negative. On in vitro tests total IgE were 44 kU/l and IgE for peach, cherry, Prup 3, Prup 1, Bet v 1, Bet v 2, Bet v 4 were negative. SPT with Prup 3 UniCAP device (cellulose polymer in a plastic reserve highly binding allergen protein) was negative. An oral food challenge, performed at rest using a commercial peach juice, scored negative. An immunoblot analysis performed with peach extract was negative. DISCUSSION: The main peculiarity of this case of FDEIA is the discrepancy between positive SPT and negative in-vitro findings. The positive SPT with the commercial peach extract suggested hypersensitivity to lipid transfer protein; however, no IgE reactivity to rPrup 3 was found in-vitro. The negative immunoblot analysis, possibly caused by the low levels of specific IgE, did not allow us to investigate the nature of the relevant allergen protein further. It is possible that this patient reacted to a different peach allergen or, alternatively, that he recognized an isoform of LTP that is different fr-om that in Uni-CAP. CONCLUSION: This case emphasizes once more the diagnostic relevance of SPT with extracts and fresh material to be performed before investigating IgE reactivity to single allergen components in-vitro. PMID- 21980801 TI - Anaphylaxis caused by tomato lipid transfer protein. AB - This study reports an unusual case of anaphylaxis induced by tomato. Inhibition studies carried out in-vitro showed the complete cross-reactivity between the relevant tomato allergen and purified peach lipid transferprotein (LTP). Tomato LTP may sometimes cause severe allergic reactions. PMID- 21980802 TI - Hen egg hair mask-induced food allergy: a case report. AB - We report the case of a 46-year-old woman who treated her hair with a homemade egg-white based mask. After one year of weekly applications, the ingestion of egg triggered rhinitis, choking and systemic urticaria. Though the breakdown of oral tolerance to egg has been reported elsewhere in the literature, to the best of our knowledge, this is the first case of hair mask-induced allergy. PMID- 21980803 TI - Atypical presentations of celiac disease. AB - Celiac disease (CD) has a wide variety of clinical presentations; together with the "classical form", in which the intestinal symptomatology is prevalent, there are "atypical forms" with predominating extra-intestinal clinical features, and the "silent form", with no clinical symptom. The "atypical forms" of the disease are characterized by few or no gastrointestinal symptoms, and predominating extra intestinal features such as neurologic, dermatologic, hematologic, endocrinologic, reproductive, renal, psychiatric, skeletal, and liver involvement(s). Silent presentation of CD may be identified through screening of high-risk groups. Today, it is well known that CD might account for several chronic health issues, so it is essential for healthcare professionals to have a high level of suspicion for the atypical presentations of CD. PMID- 21980804 TI - Pulmonary tuberculosis in infants under one year of age. AB - This study describes the clinical and radiological features of tuberculosis in infants under one year of age. Medical records were reviewed for infants aged 12 months or less with proven tuberculosis. Six patients' data were evaluated. Cough and tachypnea were the major symptom and sign, respectively. Contact with an adult case of tuberculosis was present in five of the cases. Tuberculin skin test was positive in only one case. Mycobacterium tuberculosis was cultured from gastric aspirates of four of five infants and from cerebrospinal fluid in one case. Consolidation was the most common parenchymal lung lesion occurring in four of the patients. Mediastinal or hilar lymphadenopathies were also detected in four of the patients and calcifications were seen within the enlarged nodes in two of them. Antituberculous treatment appeared to be well tolerated without significant adverse effects. Significant radiological improvement was noted after a mean period of 4.6 months. PMID- 21980805 TI - Nosocomial infections due to Acinetobacter baumannii in a pediatric intensive care unit in Turkey. AB - The aim of this study is to document the clinical characteristics and outcomes of Acinetobacter baumannii infections in pediatric patients in a pediatric intensive care unit (PICU) in Turkey. The ages ranged from 1 month to 16 years with a mean age of 55.5 months, and the male-to-female ratio was 1:1.5. Ventilator-associated pneumonia (10 patients) was the leading diagnosis, followed by catheter-related blood stream infection (4 patients), and bacteremia and ventilator-associated pneumonia associated with meningitis (1 patient) due to A. baumannii. Mechanical ventilation (93.3%), central venous catheter (73.3%), urinary catheter (93.3%), and broad spectrum antibiotic usage (80%) were the frequently seen risk factors. Neuromuscular (40%) and malignant (26.7%) disorders were the most common underlying diseases. Nosocomial A. baumannii is commonly multidrug-resistant, prolongs the length of stay in the PICU and increases the mortality rates in pediatric critical care. PMID- 21980806 TI - Fetal malnutrition and its impacts on neonatal outcome in preterm infants. AB - Fetal malnutrition is an important risk factor for both early and late neonatal outcome and adult diseases. In this study, we aimed to investigate the incidence and characteristics of fetal malnutrition and its impacts on early neonatal morbidity and mortality in preterm infants by using the clinical assessment of nutritional status score (CANSCORE). Preterm infants whose gestational ages were between 28-34 weeks were included in the study. Detailed prenatal and natal history, anthropometric measurements, and intrauterine growth status were defined, and CANSCORE was applied to all infants. Infants were separated into two groups according to total score as malnourished (total score < 25) and well nourished (total score > or = 25). Early and late neonatal morbidities, which were observed during the clinical progress, were noted in all infants. A total of 93 preterm infants were enrolled in the study. The incidence of fetal malnutrition was 54.8% (n = 51) in all infants. The incidences of maternal hypertension and preeclampsia, oligohydramnios and disturbed umbilical artery Doppler flow in the prenatal period and the incidences of neonatal hypoglycemia, polycythemia, feeding intolerance, and necrotizing enterocolitis in the postnatal period were significantly higher in preterm infants with fetal malnutrition. Fetal malnutrition contributes significantly to many early and late neonatal morbidities in preterm infants, and it should be identified in every preterm infant in the first days of life for predicting neonatal outcome, even though they are appropriately grown. PMID- 21980807 TI - Evaluation of adipocytokines in obese children with insulin resistance. AB - Obesity and overweight are among the most serious health problems in western societies and an increasing problem in developing countries. Recent studies indicate an important role of adipose tissue hormones, or "adipokines", in obesity-associated complications. To investigate the relation of two circulating adipokines (visfatin, adiponectin) with markers of insulin sensitivity and obesity in children, 40 obese children and 40 control children were recruited. Homeostasis model assessment for insulin resistance (HOMA-IR) and visfatin levels (4.99 +/- 2.08 vs. 1.47 vs. 0.7, p < 0.001; 31.3 +/- 11.1 vs. 18.5 +/- 10.7, p < 0.001, respectively) were significantly elevated and adiponectin levels (2.01 +/- 1.02 vs. 12.5 +/- 6.2, p < 0.001) were significantly lower in the obese group. Comparisons of the clinical and metabolic characteristics between insulin resistant and noninsulin-resistant groups in obese children are summarized. The insulin-resistant group had higher visfatin levels (36 +/- 9.7 vs. 22.9 +/- 7.6, p < 0.001) and lower adiponectin levels (1.7 +/- 1.05 vs. 2.5 +/- 0.77, p: 0.016). Visfatin was correlated positively and adiponectin was correlated negatively with body mass index standard deviation score (BMI-SDS) and HOMA-IR. The role of various adipokines as connectors between obesity and diabetes mellitus has been better elucidated in recent years. Based on the findings of this study, visfatin and adiponectin levels can be used as specific markers for insulin sensitivity. PMID- 21980808 TI - Is basal serum 17-OH progesterone a reliable parameter to predict nonclassical congenital adrenal hyperplasia in premature adrenarche? AB - To determine the critical features for the diagnosis of nonclassical 21 hydroxylase deficiency (NC210HD) without performing adrenocorticotropic hormone (ACTH) test, we studied 186 cases with premature adrenarche. Clinical and laboratory features as well as basal 17-hydroxyprogesterone (17-OHP) were analyzed to determine factors important for differentiating NC21OHD. Overall, 6 patients (3.2%) had ACTH-stimulated 17-OHP > 10 ng/ml. A cutoff level of 2 ng/ml for basal 17-OHP was 66.7% sensitive and 78% specific for NC21OHD; however, a cutoff level of 1.55 ng/ml had higher sensitivity (83%) and specificity (70.6%). A cutoff of 1.55 ng/ml would lead to 31% of cases with premature adrenarche having to undergo ACTH test, and only one case would have been missed. That case had a bone age SDS > 2. Three cases out of five with a basal 17-OHP > 5 ng/ml had stimulated 17-OHP < 10 ng/ml. A cutoff of 1.55 ng/ml for basal 17-OHP together with bone SDS > 2 in those with lower basal levels as a guide for carrying out an ACTH test may yield better results in the diagnosis of NC21OHD in the premature adrenarche population. A cutoff of 5 ng/ml for basal 17-OHP should not be used for diagnosis of NC21OHD. PMID- 21980809 TI - Psychiatric symptoms of adolescents reared in an orphanage in Ankara. AB - This study compared male adolescents in an orphanage with adolescents raised by their families in terms of psychiatric symptoms, using the Brief Symptom Inventory. Anxiety, depression, negative self, hostility, and Global Severity Index points were significantly higher in adolescents in the orphanage, although they did not reach pathological levels except with respect to hostility. Adolescents reared in orphanages scored high points for hostility, reaching pathological levels. PMID- 21980810 TI - Evaluation of efficacy of immunotherapy in children with asthma monosensitized to Alternaria. AB - In this study, we aimed to evaluate the efficacy of specific immunotherapy (SIT) in children monosensitized to Alternaria. Sixteen children with bronchial asthma monosensitized to Alternaria were enrolled in the study. Patients were divided into two groups as the immunotherapy group (Group I; 9 patients) and control group (Group II; 7 patients). A significant reduction in bronchial responsiveness to methacholine and Alternaria was found in Group I after one year of SIT (p = 0.03, p = 0.006) in comparison to controls. Specific IgE levels were decreased in the immunotherapy group (p = 0.001). Following allergen provocation, a rise in sputum eosinophil count was found to be lower in the SIT group compared to controls after one year (p = 0.011), and sputum eosinophil cationic protein (ECP) levels did not change in the SIT group, while there was a statistically significant increase in controls. Our results demonstrated that SIT with Alternaria caused clear changes in airway responsiveness and serum-specific IgE levels. However, further long-term studies in large series should be carried out for clinical documentation of the efficacy of SIT in the treatment of children with Alternaria allergy. PMID- 21980811 TI - Arachnoid cysts in childhood with endocrinological outcomes. AB - Arachnoid cysts are mainly manifested with the consequent neurological disorders. Even though these cysts may interfere in many systems due to their localizations, there is little information concerning their involvement in endocrinological disorders. We emphasize endocrinological functions together with cyst localizations and neurological disorders in childhood. A total of 50 patients diagnosed with arachnoid cysts were screened for cyst localizations, neurological symptoms and endocrinological outcomes evaluated by pubertal and growth status and hypothalamopituitary insufficiency. We investigated the interactions of these parameters. Arachnoid cysts were localized mostly in the middle fossa (54%) and posterior fossa (26%). Middle fossa cysts had a strong predilection for male gender (66.7% male) and left hemispheric dominancy (77%). We detected growth hormone deficiency in six patients, obesity in six patients and central precocious puberty in one patient; cysts were in the temporal area in three of the obese cases. All patients in our study had normal levels of cortisol, thyroid hormones and prolactin. In pediatric patients with arachnoid cysts, endocrinological follow-up is crucial as neurological outcomes and further evaluations are needed, mainly to confirm pubertal and growth status. PMID- 21980812 TI - Penile size in term newborn infants. AB - The objective of this study was to establish standard penile size in healthy full term Turkish newborns and to evaluate the relation between penile and other anthropometric measures. For this prospective study, stretched penile length (SPL) and penile diameter (PD) of live-borns delivered in our hospital between September 2007-December 2008 were measured, and their birthweight, length and head circumference were recorded. Penile versus other anthropometric correlations were determined by Pearson analyses, followed by linear regression. In 1217 full term subjects, mean SPL was 3.16 +/- 0.39 cm (+/- 2.5 SD = 2.19-4.14 cm), and mean PD was 1.21 +/- 0.11 cm (+/- 2.5 SD = 0.93-1.49 cm). Linear regression analysis showed a strong correlation of SPL (p = 0.0001) to height, and PD to height (p = 0.0001) and birthweight (p = 0.002). Formulas were calculated for predicted individual values for PL and PD of newborns. In conclusion, there is a correlation between neonatal anthropometric measurements and penile anthropometry. Mean anthropometric differences of various ethnicities may account for the differences in mean SPL and PD among various ethnic populations. PMID- 21980813 TI - Determination of cardiac reserve in preterm infants. AB - We aimed in this study to determine the cardiac reserve in preterm infants with phonocardiogram. One hundred and fifty-four preterm infants participated in this study. The ratio of the first heart sound to the second heart sound (S1/S2), the ratio of diastolic to systolic duration (D/S) and the cardiac contractility change trend after stimulation (CCCTS) were measured in all infants. The preterm neonatal S1/S2 decreased with increasing gestational age, but the differences between each gestational stage were not significant (p > 0.05), while the D/S significantly increased with increasing gestational age (p < 0.05). After crying induced by vaccination, the D/S was significantly lower than that in quiet state at each gestational stage (p < 0.05). The CCCTS increased with increasing gestational weeks, but the differences between each gestational stage were not significant (p > 0.05). PMID- 21980814 TI - Obesity in adolescents with celiac disease: two adolescents and two different presentations. AB - Celiac disease (CD) usually presents with diarrhea and growth retardation in childhood. Obesity is one of the paradoxical conditions in children with CD. We present two adolescents with CD and obesity. One of these patients was diagnosed as CD with malnutrition. His body weight had returned to normal after a gluten free diet, and after stopping the diet, he had become obese. The second patient was an obese adolescent presenting with dyspeptic symptoms who was diagnosed as CD. Although rare, pediatricians should remember that obesity might be seen in CD before or after the diagnosis. PMID- 21980815 TI - The first report of West Nile virus infection in a child from Turkey. AB - Seroprevalence data indicate that West Nile virus (WNV) activity is present in Turkey; however, no pediatric cases of WNV infection have been reported to date. WNV is an emerging flavivirus in Turkey, and in September2010, the Turkish Ministry of Health reported the first seven cases of laboratory-confirmed WNV infection from five different cities in the western part of the country. This is the first report of a child from central Anatolia, indicating the existence of the virus in other regions of the country. PMID- 21980816 TI - Atypical presentation of antrochoanal polyp in a child. AB - Antrochoanal polyp is a benign, solitary polypoid lesion arising from the edematous mucosa of the maxillary sinus and extending through the maxillary ostium into the nose. In children, it constitutes 33% of all nasal polyps. It presents most commonly with unilateral nasal obstruction and purulent rhinorrhea. Surgery is the usual treatment for antrochoanal polyps. The primary aim of treatment for antrochoanal polyp must be complete removal with total cleaning of the maxillary sinus. In this article, we present a case of a 13-year-old boy with an antrochoanal polyp who complained of difficulty in breathing and swallowing; the differential diagnosis of nasopharyngeal masses and the treatment of antrochoanal polyps in children are also discussed. Antrochoanal polyps present most commonly with unilateral nasal obstruction; however, they sometimes present atypically. Clinical manifestations may mimic other neoplasms in the nasal cavity and nasopharynx. Nasopharyngeal masses must be evaluated by endoscopic examination and radiologic imaging before surgery to avoid unnecessary and harmful surgical techniques. Reporting this case is important to direct attention of the Ear, Nose and Throat specialist and pediatricians when facing similar cases. PMID- 21980817 TI - A large intracardiac fungus ball in a premature infant. AB - We present a premature infant with large intracardiac mass. She had a history of sepsis and umbilical venous catheterization in the neonatal period. Twenty-seven days after withdrawal of the catheter, a precordial murmur was noted. A large right atrial highly mobile mass suspected to be thrombus was detected by echocardiography. C-reactive protein was elevated. Three blood cultures were negative. Anticoagulation treatment was started. After one week, no resolution of the thrombus was observed. The mass was surgically resected and diagnosis of thrombus infected by fungi was made on histopathological examination. Early screening of cardiac chambers by echocardiography is recommended in all preterms with intravascular catheterization. PMID- 21980818 TI - Disseminated BCG as a unique feature of an infant with severe combined immunodeficiency. AB - Severe combined immunodeficiency (SCID) is a rare primary immunodeficiency disease, which renders patients prone to recurrent severe infections in early childhood. Herein, we present a five-month-old boy with SCID who was referred to our center with recurrent diarrhea, respiratory infection and lymphadenopathy. Immunological studies showed hypogammaglobulinemia and low number of T-cells, which was compatible with the diagnosis of T- B+ SCID. An advanced cytomegalovirus pneumonitis was detected based on the results of lung necropsy. Cultures and polymerase chain reaction studies of bone marrow aspirates and spleen specimen were indicative of Mycobacterium bovis. This report emphasizes the importance of lymphadenopathy as a sentinel sign of immunological disorders. Underlying immunodeficiency diseases such as SCID should be considered in the differential diagnosis of an infant with infections and lymphadenopathy, particularly in the regions with routine national Bacillus Calmette-Guerin (BCG) vaccination. PMID- 21980819 TI - Perianal giant condyloma acuminata in an infant: an alarming lesion for a pediatric surgeon. AB - Condyloma acuminatum (CA), which is a large cauliflower-like tumor, has been linked to human papilloma virus (HPV) types associated with skin warts. It is an uncommon condition in children, and there is no consensus regarding the optimal treatment. HPV may be acquired via sexual transmission, vertical transmission or extragenital contact. We report herein a 1.5-year-old girl with perianal giant CA, which developed due to extragenital contact and consisted of HPV types 6 and 18, to emphasize the effectiveness of surgical excision. PMID- 21980820 TI - Prenatally detected congenital cystic adenomatoid malformation and postnatally diagnosed trisomy 13: case report and review of the literature. AB - Congenital cystic adenomatoid malformation (CCAM) is a rare bronchopulmonary malformation characterized by loss of the normal pulmonary tissue. CCAM may be frequently associated with cardiac and renal anomalies. Rarely, CCAM may be seen with chromosome abnormalities. This is the first reported neonatal case of prenatally detected CCAM and postnatally diagnosed trisomy 13. PMID- 21980821 TI - Hepatic laceration as a life-threatening complication of umbilical venous catheterization. AB - Umbilical venous catheterization is an intravenous infusion route for maintenance fluids, medications, blood products, and parenteral nutrition in preterm neonates. However, this procedure may be associated with several complications, such as infection, thrombosis, vessel perforation, and cardiac and hepatic injuries. Hepatic laceration is a rare but life-threatening complication of umbilical venous catheterization that is a result of direct injury through the liver parenchyma. Here, we present a preterm newborn with hepatic laceration as a rare and serious complication of umbilical venous catheterization. PMID- 21980822 TI - A case with oto-spondylo-mega-epiphyseal-dysplasia (OSMED): the clinical recognition and differential diagnosis. AB - The oto-spondylo-mega-epiphyseal-dysplasia (OSMED) phenotype is an autosomal recessive trait that is a skeletal dysplasia with the hallmark findings of limb shortening, multiple skeletal and radiological abnormalities, mid-face hypoplasia with a flat nasal bridge, small upturned nasal tip, and sensorineural hearing loss. A 3.5-year-old girl born to consanguineous Turkish parents had characteristic facial features at birth: mid-face hypoplasia, mild hypertelorism, upslanting palpebral fissures, prominent supraorbital ridges, depressed nasal bridge, small upturned nasal tip, long philtrum, and micrognathia. Radiological examination at three years of age revealed large flaring metaphyses and wide flat epiphyses. The humerus and femur showed the characteristic dumbbell shape. She had bilateral hearing loss with no ophthalmologic findings. There is continuing debate over the clinical overlap and differential diagnosis of OSMED syndrome. The patient was examined considering Weissenbacher-Zweymuller, Stickler type 3, Marshall syndrome, and Kniest dysplasia as possible differential diagnoses. We believe that the presented patient clinically manifested features of OSMED syndrome. We would like to point out that the management of OSMED calls for a coordinated multidisciplinary approach. PMID- 21980823 TI - Asperger's disorder and Williams syndrome: a case report. AB - Williams syndrome (WS) is a genetic disorder caused by the hemizygous microdeletion in chromosome 7q11.23. It is characterized by dysmorphic face, cardiovascular disease, idiopathic hypercalcemia, mental retardation, and an uneven profile of cognitive-linguistic abilities and deficits. The presence of autistic features in individuals with WS is a controversial issue. While there are reports that describe them as overly friendly with excessive sociability and good empathic skills, some recent studies focus more on the qualitative impairment of their social abilities. Here, we report the clinical presentation and follow-up of an eight-year-old boy with WS and clear problems in his social interaction, non-verbal communication and circumscribed interests. To our knowledge, this is the first case report on the coexistence of WS and Asperger's disorder. It also differs from previous papers on the comorbidity of WS and autism spectrum disorders, by depicting a highly verbal, nonretarded child followed for seven years through adolescence. PMID- 21980824 TI - Did the patient have Reye syndrome? PMID- 21980825 TI - Airway allergy and viral infection. AB - There are complex interactions between airway allergy and viral infection. Available evidence suggests that viral respiratory infection can initiate, maintain and activate exacerbation of allergic conditions in respiratory tract. Innate and inflammatory responses to acute viral infection play important roles in its relationship to allergic reactions. On the other hand, biased immune responses toward Th2 caused by an allergic reaction may make the immune response ineffective in combating viral infection. It was previously shown that allergy can increase the expression level of rhinovirus receptors on mucosal epithelial cells. This suggests that airway allergy may increase the risk of rhinovirus infection. We have recently shown that allergy may also increase the expression level of influenza virus receptors. This suggests that airway allergy and viral infection may have a reciprocal interaction. The effect of allergy on the risk and outcome of viral infection needs to be further confirmed in clinical studies and its potential implication for clinical practice should be considered. PMID- 21980826 TI - Prevalence and risk factors for early presentation of asthma among preschool children in Taiwan. AB - BACKGROUND: Traditional asthma prevalence surveys were based on the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, which focuses on children aged 6-7 and 13-14. However, asthma-like symptoms usually commence in preschool aged children, in whom it is difficult to make a definite diagnosis of asthma. It is worth determining the prevalence rate of asthma or asthma-like symptoms and analyzing the risk factors for this phenomenon among preschool aged children. METHODS: Children aged 3-6 years were recruited from kindergartens in Keelung City, northern Taiwan. The questionnaire used was based on the ISAAC phase III core and environmental questionnaires and included questions on asthma, rhino-conjunctivitis, and eczema, along with questions to elicit common and early presentations of asthma, as well as other demographic and environmental data. The questionnaires were delivered and completed by parents. RESULTS: 2395 questionnaires were delivered to parents with children at 50 kindergartens, of which 2170 questionnaires were returned (return rate 90.6%). 9.9% of these preschool children had physician-diagnosed asthma. However, 20.4% of them experienced asthma like symptoms while attending kindergarten. Both the physician diagnosed asthma and asthma-like symptoms groups had more clinical symptoms in all seasons except summer, compared to children without asthma. It was significant that the asthma-like symptoms commenced after joining a kindergarten (p < 0.001), and 66.5% of the children started to experience the symptoms within one month of beginning kindergarten. Using antibiotics or antipyretics in young infancy and mothers having asthma were the risk factors for developing asthma and asthma-like symptoms (p < 0.001), but parental smoking was not contributory to asthma development in preschool children. More frequent use of antipyretics in a year had a higher risk for the development of asthma and asthma-like symptoms. CONCLUSIONS: Asthma and asthma-like symptoms were common in preschool children. Early infection of the respiratory tract and use of antibiotics were associated with presentation of symptoms. Attending a kindergarten is also a risk factor for early presentation of asthma among preschool children. PMID- 21980827 TI - The effect of montelukast on bronchial hyperreactivity and lung function in asthmatic children aged 6-13 years. AB - BACKGROUND: Cysteinyl leukotrienes have been shown to play an important role in the pathogenesis of asthma. The effect of the leukotriene receptor antagonist, montelukast, on bronchial hyperreactivity (BHR) as measured by the methacholine challenge test in school childre in has not been reported. OBJECTIVE: To determine the effect of montelukast (Singulair) on BHR measured by methacholine challenge and lung function tests in Thai asthmatic children aged 6-13 years. MATERIALS AND METHODS: This was a randomized double-blind, placebo-controlled, crossover study performed in 29 mild to moderate persistent asthmatic children aged 6-13 years. Each child received crossover treatment with 6 weeks of montelukast (5 mg/day) and 6 weeks of placebo separated by a two-week washout period. RESULTS: The improvement of FEV1 and FEV1/FVC after 6 weeks of treatment wa significantly higher in montelukast group compared to those of placebo group (p < 0.05) After 6 weeks of treatment, mean PC20 (+/- SEM in the placebo group (5.7 +/- 1.41 mg/ml) was lower than in montelukast group (6.8 +/- 1.7 mg/ml) but there was no significant difference (p = 0.79). CONCLUSION: Montelukast significantly improved FEV1 and FEV1/FVC but not BHR in mild to moderate persistent asthmatic children aged 6-13 years after the 6 weeks of treatment. PMID- 21980828 TI - Long-term monotherapy with suplatast tosilate in patients with mild atopic asthma: a pilot comparison with low-dose inhaled fluticasone. AB - BACKGROUND AND OBJECTIVE: Suplatast tosilate is a Th2 cytokine inhibitor that is effective for controlling persistent asthma. However, the long-term efficacy of suplatast is unknown. We compared the clinical efficacy of long-term monotherapy with suplatast tosilate with a low dose of inhaled steroids in patients with mild atopic asthma. METHODS: A total of 32 patients with mild atopic asthma were randomly assigned to receive suplatast (n=15) or fluticasone (n=17). In the suplatast group, 100 mg of suplatast was given orally 3 times a day (total daily dose = 300 mg) for 2 years. In the fluticasone group, 100 pg of fluticasone was inhaled twice a day (total daily dose = 200 tg) for 2 years. RESULTS: In the suplatast group, the improvements in peak expiratory flow (PEF) rate and forced expiratory volume in 1 second (FEV1) and the changes in the symptom diary scale and frequency of beta2 stimulant inhalation were generally similar to those in the fluticasone group, and efficacy was maintained for 2 years. Improvements in inflammatory indices, such as the sputum eosinophil cationic protein (ECP) level and exhaled nitric oxide concentration, were comparable in the suplatast and fluticasone groups. The improvement in airway hyperresponsiveness was also similar in the 2 groups. The peripheral blood eosinophil percent change, serum ECP level, and total IgE antibody titer improved only in the suplatast group. CONCLUSIONS: Long-term treatment with suplatast significantly improved symptoms and inflammatory indices in patients with mild atopic asthma. Along with fluticasone, suplatast is considered a useful drug for the management of mild atopic asthma. PMID- 21980829 TI - The standard range of peak expiratory flow rates of Korean children. AB - BACKGROUND: The importance in asthma management of monitoring of peak expiratory flow rate (PEFR) has been emphasized. OBJECTIVE: For effective asthma management in Korean children, we established reference ranges for the PEFR in children 4-18 years of age. METHODS: The Mini Wright Peak Flow Meter (MWPFM) and spirometry were used in this study. All tests were conducted using a standardized method recommended by the American Thoracic Society. RESULTS: From a total sample of 2389 children, 826 (34.5%) were excluded based on our exclusion criteria. For both sexes, the PEFR increased with height, age, weight, sitting height and body surface area (BSA). Height and BSA were found to be better predictors of PEFR than the other parameters. The correlation coefficient between FEV1 and PEFR using the MWPFM was 0.886 (p < .001). The reference values of PEFR for height in our study were higher for both sexes than for those previously reported in Korea (p < .005). When we compared our results with those from other countries, the values for boys of the same height were lower than those for European children, but higher than those for African and Turkish children (p < .001). CONCLUSIONS: We have established reference values for PEFR obtained by MWPFM in Korean children in Seoul, and have provided the percentile curves for PEFR as a function of height asthma to assist clinical practices in treating children with asthma in Korea. PMID- 21980830 TI - A new proposal for a clinical-oriented subclassification of baboon syndrome and a review of baboon syndrome. AB - OBJECTIVE: To review baboon syndrome (BS). DATA SOURCES: Date sources were obtained from PubMed and Google Scholar: Photographs of baboon syndrome were obtained from our patient. STUDY SELECTIONS: PubMed and Google Scholar were searched up to June 30, 2010. The search terms were "baboon syndrome", "SDRIFE" and "thimerosal allergy". Reverse references from relevant articles and Google Scholar were also used. As BS is a classical disease and cases of offending agents were relatively old, some references were more than five years old. In order to gather as many cases of offending agents as possible, more than 50 references were collected. RESULTS AND CONCLUSION: We divided BS into as 4 groups; classical baboon syndrome, topical drug-induced baboon syndrome, systemic drug-induced baboon syndrome and symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). The pathomechanism of BS is still unknown. A delayed type of hypersensitivity reaction, a recall phenomenon, pharmacologic interaction with immune-receptors and anatomical factors may be involved in the causation of BS. PMID- 21980831 TI - Clinical features and course of pemphigus in Thai patients. AB - BACKGROUND: Pemphigus is a rare, organ-specific autoimmune disease. The epidemiology and clinical course vary between reports from different countries. OBJECTIVE: To evaluate clinical manifestations, investigation and clinical course of Thai patients with pemphigus. METHODS: Demographic data, clinical presentations, laboratory investigations and treatment outcomes in 124 pemphigus patients who had attended the specialized autoimmune skin clinic at Siriraj Hospital during the period from January 1991 to December 2009 were retrospectively studied. RESULTS: Of the 124 pemphigus patients, 79% were diagnosed with pemphigus vulgaris (PV) and 15.3% with pemphigus foliaceus (PF). The male to female ratio was approximately 1:2 in both groups. The mean age of onset was 45.4 years in PV patients and 57.4 years in PF patients. Oral mucosal involvement at the onset of disease was presented in 37.8% of PV patients. The sensitivity and specificity of DIF in the diagnosis of pemphigus was 97.8% and 98.3% while that of IIF was 94.7% and 98.4%. Disease control was achieved in 93.9% of PV patients and 94.7% of PF patients. Remission (off therapy) was achieved in 31.6% of patients in both groups. CONCLUSIONS: PV is the most common subtype of pemphigus in Thailand and usually affects females more than males. The disease usually occurs in the fifth decade of life and mucosal involvement is common. Immunofluorescence studies yields very high sensitivity and specificity. Corticosteroids are the mainstay of treatment. The majority of patients attain disease control and one-third of them achieve remission (off therapy). PMID- 21980832 TI - Significance of interleukin-17A in patients with nasal polyposis. AB - BACKGROUND: Interleukin-17A (IL-17A) is a key inflammatory cytokine in many disorders, while the significance of IL-17A in nasal polyposis (NP) is still obscure. This study aimed to investigate the expression of IL-17A in nasal polyps from both atopic and nonatopic patients and its associations with clinical and histological features. METHODS: In all, 30 patients with NP were included, and were grouped into atopic and nonatopic patients according to skin prick test (SPT). Disease severity was evaluated by symptom score, endoscopy score and CT score. Histological characteristics were assessed by eosinophilic infiltration, basement membrane (BM) thickness, epithelial damage, squamous metaplasia, and goblet cell hyperplasia. IL-17A expression in polyps was detected by ELISA and immunohistochemistry. RESULTS: Endoscopy score and CT score were significantly higher in atopic NP patients than in nonatopic NP patients (p < 0.05). IL-17A levels were significantly upregulated in both atopic (p < 0.01) and nonatopic (p < 0.05) patients versus controls. Furthermore, IL-17A levels were significantly higher in the atopic group versus nonatopic group. Significantly positive correlations were found between IL-17A levels and CT scores, eosinophilic infiltration and BM thicknesses. CONCLUSIONS: These results indicated that expression of IL-17A was significantly upregulated in NP patients and was more severe in atopic NP patients, suggesting that IL-17A may play an important role in the pathology of NP and atopy may contribute to NP by stimulating the production of IL-17A. PMID- 21980833 TI - Effect of glucocorticoid in mice of asthma induced by ovalbumin sensitisation and RSV infection. AB - OBJECTIVE: To investigate the inflammatory changes and the airway hyper responsiveness in the asthma mouse model infected by respiratory syncytial virus and elucidate the relationship between the infection and the effect of glucocorticoid. METHODS: 60 BALB/c mice were randomly divided into 6 groups. One of these is the control group; the others are the OVA/sham group, the OVA/sham +Dex group, the PBS/RSV group, the OVA/RSV group and the OVA/RSV+Dex group. The airway resistance was measured using a sealed body plethysmograph. Pathological slides were stained with hematoxylin-eosin, and the peribronchial inflammation was observed microscopically. The concentrations of IL-4, IFN-gamma, TGF-beta1 in lung tissues were detected by ELISA. RESULTS: Compared with the control group, the degree of the airway inflammation and hyperresponsiveness and the concentrations of IL-4/IFN-gamma, TGF-beta1 in all four OVA groups increased significantly. And there was a statistically significant difference between the OVA/sham group and the OVA/sham+Dex group, and between the OVA/RSV group and the OVA/RSV+Dex group respectively. Compared with the OVA/RSV group, there was an obvious aggravation of airway inflammation and hyper-responsiveness in the OVA/RSV+Dex group. CONCLUSIONS: Glucocorticoid significantly reduces airway inflammation and hyper-responsiveness induced by repetitive OVA challenge in the mouse model of asthma. However, the significant decrease in Th1 and increase in Th2 inflammation and aggravation of airway hyper-responsiveness in the mice in OVA/RSV group show that they are not sensitive to glucocorticoid. The effects of infection with RSV on the mouse model of asthma could be the cause of the glucocorticoid resistance during the therapy. PMID- 21980834 TI - Discordant CD38 measurement of CD8+ T lymphocytes using fluorescein conjugates in comparison with phycoerythrin conjugates. AB - BACKGROUND: We have previously shown that monitoring of CD38 expression can be used as a marker for antiretroviral drug efficacy in HIV infected patients. However, the detection of CD38 expression may be affected by the sensitivity of the fluorochrome conjugated reagent. OBJECTIVE: In this study, we determined the level of CD38 expression using PE and FITC conjugated anti-CD38 monoclonal antibodies in different groups of HIV infected patients. METHODS: The frequency and mean fluorescence intensity of CD38 expression using PE and FITC conjugated anti-CD38 monoclonal antibodies were detected by flow cytometry either alone or in combination with HLA-DR. A correlation between CD38 expression and CD4 count, the percentage of CD4 or viral load in antiretroviral drug naive HIV infected patients was performed. The results were compared with those for antiretroviral treated HIV infected patients who responsed to therapy and patients with virological failure. RESULTS: We found that while both reagents had the ability to detect a high frequency of CD38 expressing cells in untreated patients, only PE conjugated reagent provided correlation with markers for disease progression. More importantly, FITC conjugated reagent cannot monitor the increase in CD38 expression in patients who showed virological failure. CONCLUSIONS: The results from this study suggest that a cautious selection of fluorochrome conjugated reagents and a method for utilizing the data are extremely critical in the use of CD38 expression as a monitoring tool for ART efficacy. PMID- 21980835 TI - Flow cytometric CD4 enumeration of four different HIV-infected blood samples at the cost of one monoclonal antibody reagent. AB - BACKGROUND: The frequency and absolute number of CD4+ T-lymphocytes continue to be one of the major clinical markers for management of HIV/AIDS. The present standard dual-platform (DP) three-color and two-color PanLeucogating flow cytometric (FCM) methods for most developing countries are either expensive if manufacturers' monoclonal antibody reagents are used or limited due to an insufficient supply of generic reagents. Clearly, more affordable FCM methods are needed. OBJECTIVE: To develop a novel DP FCM method using biotin-streptavidin fluorochrome labeling in combination with the two standard DP methods for 4 different white blood cells (WBC) using only one monoclonal antibody reagent. METHODS: The percentage of CD4+ T-lymphocytes in 116 HIV-infected blood samples was determined using our new method. Results were compared with the two standard methods. Correlation and agreement of the pair method were determined using linear regression, Bland-Altman and percent similarity analysis. RESULTS: Our study showed that percentage of CD4+ T-lymphocyte values obtained from the new method correlated highly with the standard three-color and the two-color methods (r2 = 0.95 {n=52} and 0.97 {n=64}). The mean bias and percent similarity for the new method compared with the two standard methods were -0.53% (limit of agreement {LOA}:-5.22% to +4.16% with percent similarity of 99.28; and -0.22% with LOA of 3.42% to +2.98%, the percent similarity of 98.15, respectively. CONCLUSIONS: Our FCM method using biotin to label 4 different WBC samples followed by streptavidin staining is reliable for determination of CD4+ T-lymphocytes. Such an approach will significantly reduce the cost for monitoring HIV-infected patients in resource-limited settings. PMID- 21980836 TI - The effects of obstructive sleep apnea syndrome due to adenotonsillar hypertrophy on the cardiovascular system in children. AB - Obstructive sleep apnea syndrome (OSAS) due to adenotonsillar hypertrophy (ATH) is a common and important problem in children. OSAS can lead to significant cardiopulmonary complications, poor growth and problems with learning and behavior. Many studies in the literature show that OSAS due to ATH causes pulmonary hypertension, ventricular hypertrophy and systemic hypertension in the pediatric population. In this review, we discuss the effects of ATH on cardiac function. It is well known that as a child grows, the nasopharyngeal passage becomes enlarged, helping to improve OSAS. Based on this, we discuss the possible positive effect of this age-related improvement on the obstruction of cardiovascular disturbances. Finally, the possible relationship between the duration of OSAS and the timing of surgery with the permanency of cardiovascular disturbances is discussed. PMID- 21980837 TI - Prevalence of selective immunoglobulin A deficiency in healthy Turkish school children. AB - Immunoglobulin A (IgA) deficiency is the most common primary deficiency. We aimed to define the prevalence of IgA deficiency among healthy school children in Turkey and the differences between geographical regions. Blood samples were collected from 20,331 healthy school children from all regions across Turkey. The serum IgA levels were tested through nephelometric method, and all 108 samples with IgA levels lower than 5 g/L were tested through ELISA for IgG and IgM levels. All IgG and IgM values were within the normal range in all cases, and no concomitant deficiency was observed. Our study results showed that the selective IgA deficiency incidence was 0.52% (1:188). The highest incidence, of 1:128.7, was observed in children from the Marmara region; the Black Sea Region levels (1:132.7) were lower, and the Mediterranean levels (1:365.7) were the lowest. PMID- 21980838 TI - Hospitalizations for pediatric intoxication: a study from Istanbul. AB - The objective of this study was to describe the epidemiological features of pediatric patients hospitalized for intoxication. Data were collected from the medical records of children < or =14 years of age, admitted for intoxication in 2005-2007. Of the 2989 admissions, 330 (11%) were intoxication cases; 238 (72.1%) were <5 years old. Pharmaceutic agents were identified in 76.1%. Psychotropics were the most frequently ingested drugs (33.9%), and tricyclic antidepressants were the most common (27.1%). Non-pharmaceutic agents were identified in 79 (23.9%) patients, 54.4% of which were pesticides. The majority of all cases were accidental poisonings (90%), which occurred mostly in children <5 years old (71.5%), mainly by pharmaceutics, followed by self-inflicted intoxications (8.2%), which demonstrated the highest ratio in children >10 years old (6.7%). Intoxications are important especially among children <5 years old. Preventive measures such as implementation of the use of child-proof drug prescription bottles and efforts towards public education may reduce the risks. PMID- 21980839 TI - Physical child abuse and causative factors in Edirne, Turkey. AB - The aim of this study was to identify the frequency and causative factors of physical child abuse and any correlations with other domestic violence types. In a representative sample of 15-49-year-old married women living in Edirne chosen with stratified cluster sampling, 275 women were interviewed face-to-face in their residence or places of employment. The questionnaire used included any violent behavior of the women or their husbands toward their children as well as demographic features, habits, Marriage Relation Scales, Multidimensional Scale of Perceived Social Support, history of partner abuse, and childhood violence exposition. The physical child abuse rate was 61.1% among the women and 20.7% among the husbands according to the women's declarations. Social support was not associated with child abuse rates. Child abuse rate among the women was increased 2.7 times in the presence of the partner's child abuse, 1.6 times with each additional child, 3.1 times in the presence of a history of physical childhood abuse, and 1.9 times in the presence of a history of partner abuse. Child abuse by the husbands was increased 2.9 times in the presence of physical childhood abuse history and 2.3 times in case of partner abuse. Child abuse is widely seen although morally unacceptable in contemporary society. Violent behaviors spread out horizontally among family members and vertically through generations, although at decreasing rates. Healthcare professionals should behave in a sensitive manner and take responsibility together with those from other related fields to prevent this condition, which can result in several social complications. PMID- 21980840 TI - Management of foreign body ingestion and food bolus impaction in children: a retrospective analysis of 675 cases. AB - Although foreign body ingestion is a common problem in children, there are no clear guidelines regarding the management of ingested foreign bodies. The aim of this study was to evaluate the effectiveness of our protocol in the work-up and management of children with ingested foreign bodies. Between September 2002 and August 2010, a total of 675 children with suspected foreign body ingestion were seen in the emergency department. At initial presentation, the majority of foreign bodies were located in the stomach (n=392, 58.1%) followed by the small intestine (n=221, 32.7%) and esophagus (n=62, 9.2%). Based on our protocol, 84 (12.4%) patients were admitted at initial presentation, and 5 after a 48-hour observation period at home; 61 (9%) required prompt endoscopic removal. Sixty eight (10.1%) patients returned for endoscopic removal after a four-week observation period, and 3 (0.4%) patients underwent delayed surgery due to complications. The overall success rate of endoscopic retrieval was 96.1%. There were no major complications. The majority of ingested foreign bodies will pass spontaneously and most children can be safely observed at home. Selective endoscopic intervention is the preferable method for the removal of ingested foreign bodies in pediatric patients. PMID- 21980841 TI - Myocardial performance index by tissue Doppler in bronchopulmonary dysplasia survivors. AB - Bronchopulmonary dysplasia (BPD) survivors from the surfactant era were evaluated by echocardiography in a few studies and no significant differences were found between BPD and non-BPD children. In this study, we evaluated these children with myocardial performance index (MPI), which was obtained by tissue Doppler echocardiography (TDE) in addition to the conventional methods. Fifteen children with BPD who did not have any cardiopulmonary symptoms at the time of the study were examined. All children were studied with M-mode, two-dimensional and DE. Pulmonary artery systolic pressures (PAPs) were estimated from tricuspid regurgitant velocity, and MPI for both ventricles were obtained by TDE. Results were compared with those of term-born, age- and sex-matched control children. While the variables obtained by M-mode and DE did not differ between the groups, the right and left ventricular MPI were found to be significantly higher in the BPD group compared with the control group (mean right ventricular MPI 0.48 +/- 0.04 vs. 0.41 +/- 0.05; mean left ventricular MPI 0.47 +/- 0.05 vs. 0.39 +/- 0.06). In addition, mean PAPs values of the patients were found to be significantly higher than those of the controls (30.4 +/- 6.9 mmHg vs. 23.3 +/- 5.3 mmHg), and there was a positive correlation between PAPs and right ventricular MPI values in the BPD group (r = 0.5). While routine echocardiographic examinations revealed no difference between the groups, MPI measurements by TDE technique yielded significantly higher values in the BPD group. To this extent, our study is the first to show that survivors of BPD may, in fact, have a subclinical ventricular dysfunction. PMID- 21980842 TI - Sleep habits, parasomnias and associated behaviors in school children with attention deficit hyperactivity disorder (ADHD). AB - Considerable clinical data support an association between sleep problems and attention deficit hyperactivity disorder (ADHD). We aimed to investigate the sleep habits, associated parasomnias and behavioral symptoms in primary school children with ADHD. Forty primary school children with a clinical diagnosis of ADHD and 40 age-sex-matched healthy community controls were recruited. The Children's Sleep Habits Questionnaire providing information regarding sleep habits and nighttime and daytime symptoms was used. About 22% of children with ADHD (versus 2.9% of the controls) needed their parents to accompany them while going to sleep (p: 0.008). Transitional objects were needed by 8.1% of ADHD children in contrast to 2.9% of controls. Nightmares, overactivity during sleep, habitual snoring, and bed-wetting were significantly higher in the ADHD group. ADHD children needed significantly more time to go to sleep on school days (p < 0.02). Children undergoing evaluation for ADHD should be routinely screened for sleep disturbances. PMID- 21980843 TI - Weight, height and BMI references in Elazig: an east Anatolian city. AB - The aim of this study was to produce the growth references for Elazig children aged 6-11 years. Data were collected in eight primary schools of Elazig in 2007. Age- and gender-specific height, weight and body mass index (BMI) references were produced with LMS (Lambda-Mu-Sigma) method and compared with reported values in an Anatolian and a metropolitan city. A total of 3342 (1634 females, 1708 males) children aged 6-11 years from among 4258 students were included in the study. Age and gender-specific height, weight and BMI references were produced. The 3rd 97th percentiles were detected to be higher than the range of percentiles between 6-11-year-old children. We consider that this first local reference for Elazig will provide a useful tool for health planning and monitoring of growth and development. PMID- 21980844 TI - Clinical and laboratory features, complications and treatment outcome of brucellosis in childhood and review of the literature. AB - Brucellosis, whether in an endemic region or not, remains a diagnostic puzzle due to occasional misleading unusual presentations and non-specific symptoms. The aim of this study was to evaluate the clinical and laboratory findings, complications and treatment outcome of brucellosis in children in southeastern Anatolia, Turkey. This study focuses on the frequency of clinical and laboratory findings and complications in cases with brucellosis. Of 22 patients, 8 (36.3%) were female and 14 (63.7%) were male. Fever, malaise, lack of appetite, arthralgia, and night sweating were the main presenting symptoms overall. Hematologic complications (n=13, 59.1%) were most common, followed by skeletal (n=7, 31.8%) and cutaneous system (n=1, 4.5%). Brucellosis may affect any organ system and imitate a variety of clinical entities. Diagnosis of brucellosis should be considered whenever there is a febrile illness associated with rheumatological complaints. Consequently, early recognition of the infection, prolonged antibiotic treatment and careful long-term follow-up should improve the patient outcome. PMID- 21980845 TI - Foreign bodies in the ears in children: the experience of the Buenos Aires pediatric ORL clinic. AB - Even if foreign body (FB) insertion in the external auditory canal (EAC) is not an uncommon event, the literature based on large series is scarce. In the present study, ear FB cases observed at the Children's Hospital Gutierrez in Buenos Aires over five years of otorhinolaryngology (ORL) activity are presented, and the main findings are compared with data coming from other well-known published case series. Three hundred ninety-two injury cases were observed. Eighty percent of them occurred while the child was playing; in 328 cases (83.7%), adults were present. The retrieved FB included food items and objects usually available at home, such as pins, while fragments of toys were found in only 2 cases. These findings testify to the efficacy of regulations imposing manufacturing quality standards on toys; on the other hand, parents seem to be unaware of the risk imposed by FB insertion, since injuries usually happen under adult supervision while children are manipulating objects not adapted for their age. PMID- 21980846 TI - Understanding sleep habits and associated factors can help to improve sleep in high school adolescents. AB - We aimed to describe the sleep profiles and associated factors of poor sleep in adolescents. We gave a sleep questionnaire and Strengths and Difficulties Questionnaire to 3,441 high school adolescents (15-18 years) in Gaziantep, Turkey. Adolescents reported a requirement of 10.4 hours of sleep on average to feel their best during the day. However, total night sleep time (TNST) was 7.42 +/- 1.48 hours on school nights and 9.40 +/- 1.37 on non-school nights. TNST of > or =9 hours on both school nights and non-school nights was detected in 8.2%. Average bedtime and wake-up time were 23:16 and 06:41 on school nights. Bedtime was approximately 30 minutes later on non-school nights. The shift in wake-up time was nearly 2.5 hours. Statistical analysis by logistic regression model showed that TNST was most significantly correlated with school start time (morning versus afternoon) irrespective of school or non-school nights. TNST on school nights was negatively correlated with age, passive smoking at home, drinking tea/coffee, and conduct problem, whereas TNST on non-school nights was negatively correlated with the mother's education, male gender, body mass index, number of household members, and having a television in the bedroom. Daytime napping (21.3%) was associated with morning start time, age, female gender, and mother's education. Sleep-onset insomnia with sleep latency >30 minutes (21%) was not related to age or gender; however, it was associated with abnormal breathing during sleep. The findings revealed that inadequate sleep is quite prevalent among high school adolescents. Given the fact that most of the associated factors are modifiable, inadequate sleep is not inevitable for adolescents. PMID- 21980847 TI - A report of two pediatric tetanus cases. AB - Tetanus is still a difficult-to-treat disease with high morbidity and mortality. Although it most commonly occurs in non-immunized children, it can also be seen in partially immunized or immunized children. We report herein two pediatric cases of generalized tetanus. Case 1 presented with signs of acute abdomen, while Case 2 presented with the typical clinical findings of tetanus. In this report, we highlight the importance of obtaining a history of the vaccination status of pediatric patients as an essential part of the evaluation. Furthermore, the differential diagnosis of non-immunized children with abdominal rigidity should include generalized tetanus. PMID- 21980848 TI - Human 2009 influenza A (H1N1) virus infection in a premature infant born to an H1N1-infected mother: placental transmission? AB - Human infection with H1N1 virus reached pandemic status by the spring of 2009. Consequently, the rates of morbidity and mortality related with H1N1 2009 infections have been reported to be higher in pregnant women. H1N1 viremia is rare in the mother, and the risk for transmission of H1N1 2009 influenza from mother to fetus is unknown. To our knowledge, the literature contains only one previous report of a premature infant with H1N1 2009 infection whose mother also had H1N1 2009 infection. Here, we report an H1N1 pandemic influenza 2009-positive female premature infant born at 32 weeks of gestation whose mother had a confirmed H1N1 2009 infection by real-time reverse transcriptase polymerase chain reaction (rRT-PCR). This case suggests that H1N1 2009 virus might be transmitted across the placenta, and therefore, all infants born to an H1N1 2009-positive mother must be evaluated for possible H1N1 2009 infection. PMID- 21980849 TI - Acinetobacter baumannii isolation in cerebrospinal fluid in a febrile neonate. AB - We report the isolation of multidrug-resistant Acinetobacter baumannii from the cerebrospinal fluid (CSF) of a neonate suffering from fever and irritability who was initially regarded as aseptic meningitis [CSF analysis: white blood cell (WBC), 14/mm3 (neutrophil 78%); glucose, 41 mg/dl; protein, 52 mg/dl]. The normal range of WBC counts in the CSF is fairly wide, and the symptoms of meningitis are nonspecific in this age group. This patient had several risk factors for Acinetobacter infection, including exposure to antibiotics and previous admission to a neonatal care unit; therefore, it was difficult to judge the import of the isolation of A. baumannii from the CSF in this case. With the increasing prevalence of Acinetobacter species in hospital environments, clinicians may thus be confronted with uncertainty regarding whether isolated A. baumannii is a true pathogen or a contaminant. Thus, clinicians should be familiar with the risk factors for Acinetobacter infection and clinical/laboratory findings of clinically significant CSF Acinetobacter isolates. PMID- 21980850 TI - Fungemia and renal fungus ball formation with Candida norvegensis in a child with acute lymphoblastic leukemia. AB - Invasive fungal infections cause significant morbidity and mortality in pediatric cancer patients. Candida species are the most frequently isolated pathogen. Candida species may cause bloodstream and deep-seated infection in neutropenic children with cancer. The gastrointestinal system, lung, liver and spleen are the most frequently involved organs. Isolated renal involvement presented as abscess formation has been reported rarely in children with cancer. Herein, we report a patient with acute lymphoblastic leukemia (ALL) who presented with renal abscess and fungus ball formation due to Candida norvegensis, which is an unusual cause of infection. PMID- 21980851 TI - Giant mesenteric cyst of gastric origin: a case report with imaging findings. AB - We present a very rare case of a giant gastric mesenteric cyst with ultrasonography (US) and computed tomography (CT) findings. An eight-year-old boy was referred for treatment of an intraabdominal cyst, known to exist for six years. On abdominal US, a giant, thin-walled, unilocular intraabdominal cyst was demonstrated, extending from the epigastric region to the pelvis and measuring 18 x 15 x 6 cm. In contrast-enhanced abdominal CT, the cyst was demonstrated as a giant, unilocular, hypodense, non-enhancing structure, located dominantly on the right side of the abdomen. During open surgery, the cyst was found to originate from the mesentery-serosa of the gastric antrum and was filled with serous fluid. The cyst was excised totally. Both surgery and pathology confirmed the diagnosis of mesenteric cyst, originating from the stomach. The patient was discharged in good health. US and CT were effective in defining the features of the giant gastric mesenteric cyst and in narrowing the differential diagnosis in favor of mesenteric cyst. PMID- 21980852 TI - Neonatal hemochromatosis: a case report with unique presentation. AB - Acute liver failure (ALF) is a relatively rare condition in neonates, and early diagnosis and treatment are crucial for the treatable conditions. Neonatal hemochromatosis (NH) is a rare clinical condition that is clinically defined as severe neonatal liver disease associated with hepatic and extrahepatic iron deposition in a distribution similar to that seen in hereditary hemochromatosis. Although a few cases have been reported with spontaneous remission, early and aggressive medical treatment is essential for improving the outcome. Despite aggressive treatment, some patients may require liver transplantation. We report a five-day-old male infant with NH and associated Duarte variant galactosemia, renal tubulopathy and hypertyrosinemia, who was successfully treated with combination medical treatment. Combination therapy may reduce the need for liver transplantation in infants with NH. Early diagnosis and aggressive treatment are important as in galactosemia or tyrosinemia for the outcome. Thus, NH may be listed as a treatable cause of ALF in neonates. PMID- 21980853 TI - Two sisters with Bardet-Biedl syndrome: brain abnormalities and unusual facial findings. AB - Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder with a wide spectrum of clinical manifestations. BBS is predominantly characterized by dysmorphic distal extremities, obesity, structural abnormalities or functional impairment of the kidney, rod cone dystrophy, and varying degrees of mental retardation. Hypogenitalism is also present, only in males, and in all cases, facial similarities. We present herein two sisters with BBS, one of whom also had cerebellar vermis hypoplasia and cerebral and cerebellar atrophy, and both of whom had ocular abnormalities in the form of epicanthus and telecanthus and metabolic syndrome. It should also be emphasized that the occurrence of cerebellar involvement such as cerebellar vermis hypoplasia and cerebellar atrophy in BBS is very unusual. The association of abnormalities in brain development and other facial features in children with BBS is not seen frequently; thus, these abnormalities should be searched carefully. PMID- 21980854 TI - Spondyloenchondrodysplasia: a rare cause of short stature. AB - Skeletal dysplasias (osteochondrodysplasias) are a group of diseases that must be included in the differential diagnosis of disproportionate short stature. History, clinical and radiologic findings and consanguinity are important features to be considered when a specific diagnosis is investigated. Spondyloenchondrodysplasia is a very rare skeletal dysplasia characterized with enchondromas in the long bones and platyspondyly. Manifestation of the disorder may include neurological involvement (spasticity, intracranial calcifications and mental retardation) and immune dysfunction. Herein, we report a 12-year-old boy who admitted to our clinic with short stature, who was born to consanguineous parents. He presented clinical (significant widening of wrists, ankles and knees) and radiologic (enchondromatous lesions in the metaphysis of long bones) features of spondyloenchondrodysplasia but did not yet have neurologic or immunologic involvement. PMID- 21980855 TI - Gastric perforation in an extremely low birth weight infant recovered with percutaneous peritoneal drainage. AB - Neonatal gastric perforation is an uncommon but life-threatening condition, which is mainly encountered in premature infants. Primary surgical repair is the principal mode of the treatment. Gastric perforation in neonates improving with percutaneous peritoneal drainage alone has not been described previously. Therefore, an extremely low birth weight infant is presented herein in order to emphasize that gastric perforation may improve with percutaneous peritoneal drainage alone. Isolated gastric perforations in newborn infants may be improved with percutaneous peritoneal drainage alone without need for primary surgical repair. PMID- 21980856 TI - Benign monomelic amyotrophy in a 7-year-old girl with proximal upper limb involvement: case report. AB - Monomelic amyotrophy (MMA) is a benign motor neuron disease characterized by neurogenic amyotrophy, which usually affects one of the upper or lower extremities. Progression is slow and symptoms are clinically stable. Symptoms are seen in the second or third decades of life. In this study, we present a seven year-old girl who was diagnosed and directed to the Physiotherapy Department at the age of 5 years and had unilateral proximal upper limb involvement. Family history of the case was recorded. Neurologic evaluation was performed. Range of joint motion, muscle shortness and strength, posture, extremity lengths, gait, timed performance, arm function, and motor and mental maturation were assessed. The physiotherapy program was designed progressively as strengthening and resistive exercises. Motor and mental developmental milestones were normal. There was no limitation in active or passive motion of all joints. She had more flexible joints, scapula alata, asymmetry between shoulder levels, and weakness on proximal muscles of the right upper extremity. In the follow-up assessment at eight months, there was no asymmetry between shoulder levels and scapular symmetry began to improve. Female gender and involvement restricted to one proximal upper limb are rare in the literature. This patient demonstrates the positive effects of physical therapy with early diagnosis of MMA. The rapid recovery of muscle weakness shows the importance of strengthening and resistive exercises applied to specific muscles in the treatment. PMID- 21980857 TI - [Cumulative exposure to pesticide residues in food]. AB - The results of food monitoring studies indicate that humans are constantly exposed to residues ofplant protection products (pesticides) in marketed food products. Hence, assessment of the risk to consumers associated with the consumption of products containing residues of the active substances of pesticides is a key stage in both the registration of pesticides and official control of foodstuffs. However there are frequent cases of exposure not only to individual active substances but also to mixtures of pesticide residues. These levels are usually low, below of effective action, and interaction such as synergism orpotentiation is not expected to occur At the same time, literature data indicate that for mixtures sharing a common MOA (Mode of Action/Mechanism of Action), the probability of additive effects is high, even after adjusting for the low levels of the mixed pesticide residues present. Accordingly, health risk assessment for consumers exposed to such mixtures (cumulative/aggregate risk) has become an issue of topical importance. EU-level initiatives regarding the development of appropriate methodology for the estimation of cumulative/aggregate risk have brought about considerable progress in this area. The article discusses various aspects of estimation of cumulative risk for consumers associated with exposure to mixtures of pesticide residues in food. PMID- 21980858 TI - [Ubiquitous perfluorinated compounds]. AB - Perfluorinated compounds are derivatives of hydrocarbons, in which all or most of hydrogen atoms are substitiuted by fluorine atoms. These compounds are commonly used in many branches of industry. Perfluorinated compounds are in the limelight because of numerous reports concerning their toxicity and negative effects on human health as well as contradictory information about their cancerogenic effect. The above compounds are used in production of many commonly used products including such brand names as Gore-Tex, Teflon, Stainmaster. The most common ways of penetrating these compounds into a human organism are: via food, inhalation and skin contact. Perfluorooctanesulfonate (PFOS) has been added to the list of persistent organic pollutants (POPs). PMID- 21980859 TI - [Application of the quechers method coupled with gas chromatography with electron capture detection (GC-ECD) in analysis of pesticide residues in food]. AB - In 2003 Anastassiades and Lehotay described the "quick, easy, cheap, effective, rugged and safe" (QuEChERS) method for the multi-class, multiresidue analysis of pesticides in fruit and vegetables. The QuEChERS method allows to obtain high quality results with a minimum number of steps and a low solvent and glassware consumption. The QuEChERS method based on liquid-liquid partitioning with acetonitrile followed by a cleanup step with dispersive-SPE (Solid Phase Extraction). The aim of this study was to check the usefulness of the QuEChERS method coupled with gas chromatography with electron capture detection (GC-ECD) in analysis of pesticide residues in food. Ready-to-use QuEChERS reagents kits and own-weighed reagents have been applied. In recovery experiment for 15 selected pesticides, three matrices belonging to different groups--carrots (high carotenoids content), raspberry (highly acidic matrix) and tomatoes (high water content)--have been used, according to the SANC0/10684/2009 guideline and PN-EN 15662:2008 requirements. Fourteen compounds showed a recovery in the range of 70 120% and only one compound (trifluralin in raspberry) presented a recovery lower than 70% at the 0.5 mg/kg fortification level. The repeatability was satisfying with a RSD lower than 20% apart from trifluralin in raspberry (27.16%). PMID- 21980860 TI - [The study of nickel and chromium contents in dietary supplements supporting slimming]. AB - The market of dietary supplements develops extremely fast in the whole world, also in Poland. A great popularity is ascribed to preparations aiding slimming diet. The application of dietary supplements aimed at reducing body's weight is a result of trends connected with the popularity of a healthy lifestyle and the care about one's appearance. Dietary supplements produced on the basis of natural products frequently contain significant amounts of mineral compounds, including microelements indispensable for man (in strictly specified amounts), among others: nickel and chromium. The subject of the study was 16 chosen dietary supplements aiding slimming in which the levels of chromium and nickel were determined. The samples were mineralized "dry" at the temperature of 480 degrees C. The ashes were dissolved in 15%-aqueous solution of HCl (Suprapur, Merck). The levels of the investigated elements were determined in Pye Unicam SP192 Atomic Absorption Spectrometer: nickel - by the extraction method from the organic phase, chromium - directly from a mineralised substance. Determined levels of nickel ranged from 0.11 microg/g in Nivelazione-"kapsulki na noc" supplement to 3.35 microg/g in Teavera preparation, and of chromium from 0.12 microg/g (Adipobon mono) to 22.93 microg/g (Chitobon-preparation with the addition of chromium). The levels of nickel and chromium in the studied supplements were different and depended on the preparation content. The capsules of some preparations, e.g., those with the addition of organic chromium contained levels of chromium exceeding AI dose for this element. PMID- 21980861 TI - [Calcium, magnesium, iron and zinc in drinking water and status biomarkers of these minerals among elder people from Warsaw region]. AB - The aim of this study was to estimate the influence of calcium, magnesium, iron and zinc contents in drinking water on chosen parameters of nutritional status of these minerals in 164 elder people, 75-80 age, living in Warsaw region. Blood, hair and saliva were collected to assess the calcium, magnesium, iron and zinc nutritional status, while the samples of drinking water were collected to determine these minerals in water Mineral concentrations in blood, hair saliva and water were assessment using the atomic spectrophotometer absorption method It was showed that contribution of drinking water to calcium, magnesium, iron and zinc intake was: 15%, 4%, 5%, 9%, respectively. The relationship between the contents of these minerals in drinking water and their levels in the blood, hair and saliva had low correlation coefficients. It probably showed that homeostasis was maintained in the human body and other factors such as demographic or lifestyle factors were important. PMID- 21980862 TI - The content of trace elements in the diet of adolescents in Warsaw. AB - The aim of the study is to assess the contents of iron, zinc and copper in the diet among of adolescents living in Warsaw. The intake ofselected trace elements was estimated on the basis of three-day dietary records. Microelement contents in the diet were calculated using Food Composition Tables. The percentage of the RDA realization for the safe level was calculated on the basis of standards for Polish population, developed by National Food and Nutrition Institute. It was demonstrated that adolescents living in Warsaw had 50-60% copper-deficient diets. The content of iron and zinc in the diet of adolescents was about 10-40% lower than recommended. Deficiency of iron in the body causes anaemia and influences learning process, therefore the content of this element in the diet of young people is especially important. PMID- 21980863 TI - [Evaluation of fatty acids and cholesterol intake by a group of students]. AB - The main purpose of this work was the analysis of the composition of fatty acids and cholesterol. The investigation was done among 143 students, with 3-day dietary records method. The research was carried out in the years 2007 and 2008. The average fat intake was 92.7% of RDA. The intakes of saturated, monounsaturated and polyunsaturated fatty acids were 99.4%, 71.2% and 73.3% of recommended levels, respectively. The average intake of cholesterol was in accordance with recommended value 300 mg (91.00%). Intake of fat, fatty acids and cholesterol depended on gender Intake offat, saturated and monounsaturated fatty acids depended on state of health additionally. Intake of saturated fatty acids was different according to place of dwelling. In case of men too much energy from fat (37.9%) was recorded and too much intake of cholesterol (about 58%). PMID- 21980864 TI - [Energy and selected nutrients content in pre-school children diet of Warsowia district]. AB - The aim of this study was the evaluation of energy and selected nutrients content in 10 days menus (spring period) from 5 kindergartens situated in mazowiecki district. The kindergartens were located in Zyrardow, Dziekanow, Warsaw, Lomianki and Nowa Iwiczna. It was shown that amount of energy and macronutrients was unproper. Most of the food rations contained too much energy, from fat and protein, and too little from carbohydrates. Planned pre-school nutrition was not balanced properly in the meaning of energy and nutrients amount. PMID- 21980865 TI - [Assessment of dietary habits in students of the Medical University of Bialystok with differentiated nutritional status]. AB - The research was conducted into 360 students of Medical University in Bialystok with differentiated nutritional status. The study involved 251 female students (46 with underweight, 186 with normal weight, 19 with excessive body weight) and 69 male students (7 with underweight, 47 with normal weight, 15 with excessive body weight). The quantity analyze of daily food rations was conducted on the base of the previous day 24 h dietary recall method. The computer program Diet 2.0 designed in the Institute of Food and Nutrition in Warsaw was used for calculations. Energetic value and basic nutrients supply was estimated and also the average content of dietary fiber and cholesterol. The results of the conducted research indicate lack ofbalanced content ofessential nutrients in daily food rations of the tested students of both sexes, irrespective of nutritional status. Energy supply was far too low comparing to recommended standards. It was proved that carbohydrate and fat supply was definitely lower than recommended standards. The research also showed low consumption of dietary fiber in all investigated groups and high consumption of cholesterol in men. PMID- 21980866 TI - [The estimation of the influence of pattern of consumption on the possibility of blood donation by repeated blood donors]. AB - The aim of this study was to compare the diets of repeated blood donors, qualified to and disqualifiedfrom a blood donation during the course of this study, and to evaluate the impact of the diet and nutritional status on the capability of repeated donors to donate blood. The study was carried out during the autumn of 2009 in Szczecin on a group of 40 repeated blood donors who volunteered for another donation to the Regional Centre for Blood Donation and Blood Treatment (RCKiK). Analysis of the results revealed that the diet of the studied donors was inappropriate; however the men qualified without contraindications to donation consumed more nutrients involved in haematopoesis in the diet (B-group vitamins and iron), compared to men who were not allowed to donate blood. It can therefore be presumed that temporal contraindications preventing subjects from blood donations may have resulted from a poorly balanced diet. The results of this study imply that blood donors should be educated by the RCKiK as to the principles of proper nutrition, so that they would be able to compose a diet which would compensate for nutrient depletions in the body due to multiple blood donations. PMID- 21980867 TI - The effect of cultivation intensity on mineral content in grain, flakes and bran of winter wheat (Triticum aestivum L.)--preliminary study. AB - The aim of the study was to assess the effect of cultivation intensity on the Ca, Mg, Zn and Fe contents in winter wheat grain, flakes and bran. The initial material for the study comprised grain, flakes and bran of two winter wheat cultivars Kobiera and Bogatka. These cultivars were from two strain testing stations located in Lower Silesia, Zybiszow and Tomaszow Boleslawiecki in the years 2007-2008. The cultivation was conducted on two intensity levels: lower and higher The mineral content was determined by the flame atomic absorption spectrometry (FAAS). The investigation showed that the level of cultivation had no significant effect on the content of all minerals analyzed in grain, flakes and bran. The Ca content in wheat grain, flakes and bran was stable, regardless of varieties, weather conditions, tillage intensity and cultivation place, furthermore soil conditions significantly affect Fe content in wheat grain, flakes and bran. PMID- 21980868 TI - [Selected vitamins content in pre-school children diet in Warsaw and regions]. AB - The aim of this study was the evaluation of selected vitamins in the decade menus collected from five kindergartens in Warsaw and regions. The evaluation was done for 10 days menus of spring period Results shown the planned pre-school nutrition was not balanced properly related to too much amount of vitamin A, E, vitamin B and niacin and too little vitamin D and folate. PMID- 21980869 TI - [Fortified food products as a potential source of folic acid in human nutrition]. AB - The aim of the study was to analysis the number and variety offoodproducts fortified with folic acid available on the Warsaw market and to assess consumers' knowledge about these products. Information about food products was based on label declaration, in summer 2009. In addition knowledge about fortified food was studied in the group of 94 market customers. There were 166 foodstuffs fortified with folic acid from various food categories, like breakfast cereals, wheat flour, fruit juices and drinks, sweets, margarine, instant cocoa and tea instant as well as milk products. Breakfast cereals and juices, nectars and fruit drinks were the largest groups. Less than half of market customers correctly defined term 'fortified product", less than 40% of respondents answered properly on question concerning folic acid. There is possibility to increase the folates intake by consuming various products fortified with folic acid. The wide public education is essential for increasing the role of these products in nutrition. PMID- 21980870 TI - [Usefulness of flaxseed oil in the limitation of diet induced metabolic disturbances]. AB - The aim of this study was to compare the effects of different fats, that is pork lard, refined soybean oil, and unrefined, cold pressed flaxseed oil, on the antioxidant status, inflammatory markers and blood lipid profile of rats fed diets rich in fructose. Four week of experimental feeding with flaxseed oil enriched diet (16%) led to a significant decrease in the degree oflipid peroxidation in liver when compared with rats fed the same amount of pork lard. Moreover the addition of soybean oil or flaxseed oil to the diet (16%) decreased significantly triglyceride and total cholesterol blood levels, as well as reduced atherogenic index of plasma. The concentration of HDL cholesterol was retained on a higher blood level in rats fed flaxseed oil enriched diet, when compared with the soybean oil group. PMID- 21980871 TI - [Proper diet in type 2 diabetes as a means of patients' rehabilitation]. AB - The aim of the study was to specify the dietary habits of type 2 diabetes sufferers. The investigation was conducted in medical centres of the Malopolskie voivodship in 2008. Anonymous questionnaires were filled in by a group of l00 persons (66 women and 34 men) aged 40 to 84. Principles of proper nutritional behaviour were implemented to a limited extent by the ill studied. The most common dietary errors were: the lack of regular meal intake, snacking between meals, eating sweets and employing inadvisable cooking techniques. The patients' diets included fatty meats such as pate, salami, sausages. The relevant education in regard to nutritional principles in diabetes and other civilisation diseases should be realised for the patients. PMID- 21980872 TI - [The examination of humic acids in therapeutic and cosmetic products manufactured of peat base]. AB - The aim of this study was the examination of humic acids in therapeutic and cosmetic products manufactured of peat base. The raw peat, peat extracts, products (paste and therapeutic mud cubes) and peat preparations as: ointment, emulsion, gels were examined. The absorption spectra in a range UV-VIS were made for humid acids extracted from above mentioned samples and spectra of these acids fractions. Examined were: hymatomelanic acids, fluvonic acids and humic acids extracted from product made of peat and peat ointment. The differential 4th degree spectra contain correctly separated and symmetrical peaks of electromagnetic radiation wavelength characteristic for standard acid fractions. On a base of obtained differential spectra of humic acids their quantitative participation in examined materials was estimated. PMID- 21980873 TI - Diagnosis and treatment of injuries to the posterolateral ligament complex. AB - Posterolateral corner (PLC) injuries are an often unrecognized and disabling injury that frequently accompanies other ligamentous disruptions. The spectrum of injury severity and heterogeneity of treatment options have made comparison of outcomes difficult. Several clinical studies and reviews have focused on the outcomes and treatment algorithms of knee dislocations or multiligamentous knee injuries. There is, however, a paucity of data in the literature analyzing the clinical outcomes and treatment recommendations of isolated PLC injuries or PLC injuries in combination with a single cruciate ligament tear. Furthermore, to our knowledge there is no review that analyzes the different repair or reconstructive techniques and assesses the clinical outcomes of these techniques. PMID- 21980874 TI - The posterolateral corner: surgical approach and technique overview. AB - Injuries to the posterolateral corner (PLC) of the knee can lead to profound knee instability, especially when combined with anterior cruciate or posterior cruciate ligament injury. With increased recognition of this injury, as well as improved understanding of the pathoanatomy, surgical treatment of these injuries has evolved in favor of acute treatment including reconstructive techniques to minimize recurrent laxity and allow for early rehabilitation. This article describes the approach to the PLC and the technique for figure of 8 reconstruction. PMID- 21980875 TI - A military perspective to articular cartilage defects. AB - Articular cartilage injuries present a challenge in terms of definitive treatment in the United States military population. Active duty soldiers' physical demands are unlike the general population in that a military career requires soldiers to maintain a physical activity level similar to that of an athletic population. Current treatment options for the chondral defect include microfracture, osteochondral transplantation, and autologous chondrocyte implantation. These treatment modalities carry specific advantages and disadvantages and must be considered when evaluating and treating patients with chondral injuries. It is unclear which procedure is the best first-line treatment for these injuries, but newer studies are beginning to evaluate these procedures over time and in high demand populations. The purpose of this article is to review current treatment options as they relate to return to full activity of the young "combat athlete." Results of each treatment option from published data will be compared and reviewed throughout this article. PMID- 21980876 TI - Meniscus repair and transplantation techniques. AB - Modern meniscal repair incorporates multiple techniques and adjunctive measures. The classic inside-out repair remains the gold standard and is most appropriate for a bucket-handle type tear of the medial or lateral meniscus. The all-inside technique has gained in popularity recently and has outcomes that approach those of the inside-out repair with decreased morbidity but increased cost. The choice of this technique is most appropriate for small tears requiring few sutures to repair. Outside-in repair can also be employed and is preferred for anterior horn tears. Surgeons may use a hybrid technique that incorporates all techniques in some challenging cases. Meniscal debridement is used for degenerative tears that are not amenable to repair. Meniscal transplantation is an option for symptomatic meniscal deficiency in young, active patients. This article discusses the technical considerations for meniscal debridement, repair, and transplantation. PMID- 21980877 TI - Comparison of ACL fixation devices using cadaveric grafts. AB - We evaluated two newer forms of femoral fixation of hamstring grafts for anterior cruciate ligament reconstruction, the Endobutton direct (Smith and Nephew, Andover, MA) and Femoral intrafix (Depuy Mitek, Raynham, MA), and compare them to devices that have been evaluated in the literature, the AXL Crosspin (Biomet, Warsaw, IN) and Biotransfix II (Arthrex, Naples, FL). Paired hamstring tendon allografts were fixed in the femoral tunnel of 24 cadaveric bovine knees (6 per group) according to each device's specifications. The free ends (tibial sides) were fixed to the materials testing machine via custom-made cryo-clamps. In Phase I, single load to failure and stiffness were evaluated, and in Phase II, peak displacement was evaluated while cyclic loading was performed over 1000 cycles. One-way analyses of variance were performed to test for differences between groups. There were no significant differences in failure load (p = 0.42) or stiffness (p = 0.39) between the fixation devices. There was also no significant difference in peak displacement measured during the cyclic loading phase (p = 0.32). Our findings suggest that the newer generation devices, Endobutton direct and Femoral intrafix, have similar strength in single load to failure and similar peak displacement during cyclic loading as compared with clinically proven Crosspin techniques. These newer devices, which are designed to accommodate for more anatomic femoral tunnel placement, may provide a reasonable alternative without compromising biomechanical properties. PMID- 21980878 TI - Lateral patellofemoral impingement: a cause of treatable pain after TKA. AB - Multiple etiologies may cause anterior knee pain after total knee arthroplasty. While prior studies have addressed component positioning and surgical technique, no series in the literature describes lateral patellofemoral impingement as a source of the pain. Over a 2-year period at our institution, 18 patients with 19 painful total knee arthroplasties were diagnosed with lateral patellofemoral impingement. All underwent revision surgery with either lateral facetectomy or revision of the patellar dome. These patients were followed with Knee Society scores for 1 year. Knee Society scores were significantly improved at 8 weeks, 16 weeks, and 1 year. Lateral patellofemoral impingement should always be considered in the differential diagnosis of the painful total knee arthroplasty. This should be evaluated clinically through direct palpation of the lateral facet, and radiographically with the sunrise view. Lateral facetectomy or patellar revision can be performed with predictably good clinical results. PMID- 21980879 TI - Acoustic emission studies of posterior stabilized and cruciate retaining knee arthroplasties. AB - Different acoustic frequencies have been used to diagnose progression of osteoarthritis, gross pathology, and wear in knee prostheses. It is possible that detailed analysis of higher frequencies could detect and quantify the smaller geometric changes (asperities) that develop in articular prosthetic wear. In this study we evaluated the feasibility of using ultrasonic emission to determine total knee arthroplasty (TKA) type and time from implantation using a simple, handheld measurement system. We examined the ultrasound emission generated by similar designs of posterior stabilized (PS) and cruciate retaining (CR) total knee prostheses and native knees of 58 patients and 10 controls. The subjects were asked to sit, rise, sit again, and take five steps while recording the acoustic data from both knees. Acoustic emission analysis examined frequency distributions and power spectrums of the recorded signals, and their relations to prosthesis type and time from implantation. We screened 44 CR and 48 PS TKAs, as well as 24 native knees. Analysis of this data suggested a possibility of differentiating between type of implants, and a relation to time since implantation. Our data suggest that we might be able to assess the status and time from implantation of a TKA by acoustic emission signals. Further in vitro analysis of the relationship of wear to ultrasonic emission data are needed for accurate quantification of arthroplasty wear. A simple, in-office screening tool for TKA patients could indicate which patients require closer follow-up and monitoring due to risk of potential problems. PMID- 21980880 TI - Mechanical stability of cementless tibial components in normal and osteoporotic bone. AB - There is renewed interest in cementless total knee arthroplasty, yet the optimal tibial design remains elusive. The purpose of this study is to evaluate the stability of various tibial component designs in normal and osteoporotic bone. Two cementless tibial implants, a CoCr beaded keeled baseplate and a two-pegged, highly porous titanium design underwent mechanical testing in normal and osteoporotic bone models. Decreased stability was observed in both designs in the osteoporotic model compared with "normal" bone (p < 0.0017). Stability of the keeled design was greater than the two-peg design in both densities; however, this difference was statistically significant only in the "normal" bone model (p = 0.005). This study demonstrates that cementless tibial component stability is affected by both implant design and host bone quality. PMID- 21980881 TI - Percutaneous neuromodulation pain therapy following knee replacement. AB - A new device (Deepwave) utilizing percutaneous neuromodulation technology has been developed with preliminary studies demonstrating superior pain inhibition compared with transcutaneous electrical nerve stimulation. We hypothesize that the use of Deepwave is efficacious in reducing the severity of acute pain and opioid use in patients following total knee replacement (TKR) surgery. We conducted a randomized controlled trial on 23 patients who underwent primary TKR. The patients were categorized into two groups--experimental or control group. Following TKR, patients underwent either Deepwave or sham treatments. A Brief Pain Inventory questionnaire and the amount of all pain medications taken were recorded. There was a significant reduction in patient's subjective rating of pain and Visual Analog Scale score in the experimental group (p < 0.05), with a trend toward decreased opioid use but this was not significant (p = 0.09) The Deepwave device is effective in reducing the subjective measures of pain with a trend toward decreased opioid use in patients following TKR. PMID- 21980882 TI - Results of MIS TKA at mean nine year follow-up. AB - The first 103 consecutive minimally invasive total knee arthroplasties performed by a single surgeon were assessed to determine the clinical and radiographic outcomes at a mean of 9-year follow-up (range, 8 to 10 years). Patients who died before final follow-up were 10 (13 knees), leaving 90 knees in 69 patients for final review. Outcome was evaluated using Knee Society pain and functional scores. Survival with revision as an end point was 97.1%. Knee Society scores and range of motion improved significantly to a mean of 96 and 92 points and a mean of 115 degrees, respectively. There were five patients who required surgical intervention for unexplained pain with findings of retained cement and adhesions. Radiographic analysis did not reveal any progressive radiolucencies. These results suggest that excellent long-term outcomes can be achieved with minimally invasive total knee arthroplasty. PMID- 21980883 TI - Para-articular osteochondroma of the infrapatellar fat pad. AB - We report a rare case of para-articular osteochondroma of the infrapatellar fat pad. A 56-year-old woman presented with a 2-year history of mild anterior knee pain and a hard mass around the right knee. Plain radiographs and computed tomography revealed trabeculated ossification within the infrapatellar fat pad. We performed surgery through an open approach. The mass was located within the infrapatellar fat pad and did not communicate with the joint space or patellar tendon. The gross appearance of the tumor resembled an osteochondroma. On microscopic examination, it was composed of cartilaginous tissue with areas of multifocal endochondral ossification surrounded by fibrous connective tissue. There was no synovial tissue. We diagnosed it as a para-articular osteochondroma of the infrapatellar fat pad. In the literature, this entity is rare. Differential diagnosis includes a variety of bone-forming lesions including malignancy. Definitive diagnosis is made by combining clinical, radiologic, and histologic findings. PMID- 21980884 TI - Laughter in the best medicine. PMID- 21980885 TI - Patient autonomy and the twenty-first century physician. PMID- 21980886 TI - Growth attenuation: health outcomes and social services. PMID- 21980887 TI - Growth attenuation: health outcomes and social services. PMID- 21980888 TI - Growth attenuation: health outcomes and social services. PMID- 21980889 TI - Growth attenuation: health outcomes and social services. PMID- 21980890 TI - Growth attenuation: health outcomes and social services. PMID- 21980891 TI - Other people's stories. PMID- 21980892 TI - The FDA, preemption, and public safety. PMID- 21980893 TI - Prohibiting anonymous sperm donation and the child welfare error. PMID- 21980894 TI - All that glitters isn't gold. PMID- 21980895 TI - Questioning the universality of medical ethics: dilemmas raised performing surgery around the globe. PMID- 21980896 TI - No more larking around! Why we need male LARCs. PMID- 21980897 TI - What health care providers know: a taxonomy of clinical disagreements. AB - Some assume that respecting patient autonomy means clinicians should refrain from expressing opinions about what's in a patient's best interests. But depending on the kind of medical decision the patient is making, a clinician may have expertise vital to the patient's best interests-and even if she doesn't, she may still know what is best. PMID- 21980898 TI - Gallows humor in medicine. AB - Medical professionals regularly joke about their patients' problems. Some of these jokes are clearly wrong, but are all jokes wrong? PMID- 21980899 TI - Children and genetic identification of talent. PMID- 21980900 TI - Help is here. First consortia health IT grads hit the market. AB - Last year 82 community colleges launched health IT training programs in a hurry. After a slow and sometimes bumpy start, the programs are picking up steam and the students are graduating. Now comes the next test: are the jobs out there? PMID- 21980901 TI - Standardized testing. HIT pro exams test competencies in health IT roles. AB - Healthcare needs more than EHRs, it needs people who can implement and maintain them. New federally sponsored health IT exams set workforce competencies, helping job seekers demonstrate knowledge and employers benchmark qualifications. PMID- 21980902 TI - Permanent record. Electronic records aid in the aftermath of Joplin tornado. AB - When a tornado struck St. John's Regional Medical Center in May 2011, its patient records were stored in a newly launched electronic health record system, helping prevent a bad situation from being worse. PMID- 21980903 TI - Pick one. Comparing the Medicare and Medicaid EHR incentive programs. PMID- 21980904 TI - The EHR's impact on staffing models. PMID- 21980905 TI - Predictive modeling 101. How CMS's newest fraud prevention tool works and what it means for providers. PMID- 21980906 TI - PopHealth primer. ONC funds open-source software to streamline clinical quality measures reporting for meaningful use program. PMID- 21980907 TI - Problem list guidance in the EHR. PMID- 21980908 TI - New ICD-9-CM diagnosis codes for FY 2012. PMID- 21980909 TI - The musculoskeletal system and ICD-10-CM/PCS. PMID- 21980910 TI - pH-Dependent Cu(II) coordination to amyloid-beta peptide: impact of sequence alterations, including the H6R and D7N familial mutations. AB - Copper ions have been proposed to intervene in deleterious processes linked to the development of Alzheimer's disease (AD). As a direct consequence, delineating how Cu(II) can be bound to amyloid-beta (Abeta) peptide, the amyloidogenic peptide encountered in AD, is of paramount importance. Two different forms of [Cu(II)(Abeta)] complexes are present near physiological pH, usually noted components I and II, the nature of which is still widely debated in the literature, especially for II. In the present report, the phenomenological pH dependent study of Cu(II) coordination to Abeta and to ten mutants by EPR, CD, and NMR techniques is described. Although only indirect insights can be obtained from the study of Cu(II) binding to mutated peptides, they reveal very useful for better defining Cu(II) coordination sites in the native Abeta peptide. Four components were identified between pH 6 and 12, namely, components I, II, III and IV, in which the predominant Cu(II) equatorial sites are {-NH(2), CO (Asp1-Ala2), N(im) (His6), N(im) (His13 or His14)}, {-NH(2), N(-) (Asp1-Ala2), CO (Ala2-Glu3), N(im)}, {-NH(2), N(-) (Asp1-Ala2), N(-) (Ala2-Glu3), N(im)} and {-NH(2), N(-) (Asp1-Ala2), N(-) (Ala2-Glu3), N(-) (Glu3-Phe4)}, respectively, in line with classical pH-induced deprotonation of the peptide backbone encountered in Cu(II) peptidic complexes formation. The structure proposed for component II is discussed with respect to another coordination model reported in the literature, that is, {CO (Ala2-Glu3), 3 N(im)}. Cu(II) binding to the H6R-Abeta and D7N-Abeta peptides, where the familial H6R and D7N mutations have been linked to early onset of AD, has also been investigated. In case of the H6R mutation, some different structural features (compared to those encountered in the native [Cu(II)(Abeta)] species) have been evidenced and are anticipated to be important for the aggregating properties of the H6R-Abeta peptide in presence of Cu(II). PMID- 21980915 TI - Orthogonal interactions of CO molecules on a one-dimensional substrate. AB - We investigate the chemisorption structure of CO molecules on the quasi-one dimensional Cu(110)-(2 * 1)-O surface by low-temperature scanning tunneling microscopy and density functional theory. Contrary to flat metal surfaces, where CO molecules adsorb in an upright geometry and interact through repulsive intermolecular interactions, we find the most stable adsorption structure of single CO molecules to be at Cu atoms of substrate Cu-O- chains with the Cu-CO unit bent by ~+/-45 degrees in two equivalent structures at low coverages. At higher coverages, CO molecules combine in the same structure into highly ordered single-molecule-wide rows perpendicular to the substrate chains in an approximately 8 * 1 full monolayer structure. First-principles calculations attribute the unprecedented chemisorption behavior of CO molecules to lifting of the host Cu atoms by 1 A from the surface Cu-O- chains, in order to optimize the bonding and reduce the repulsive interactions with the substrate. This structural distortion enables short-range intermolecular dipole-dipole attraction and creates orthogonal long-range surface-mediated repulsion leading to unusual self assembly of CO molecules into coherent nanometer scale molecular grating structures. PMID- 21980916 TI - A reduced-amide inhibitor of Pin1 binds in a conformation resembling a twisted amide transition state. AB - The mechanism of the cell cycle regulatory peptidyl prolyl isomerase (PPIase), Pin1, was investigated using reduced-amide inhibitors designed to mimic the twisted-amide transition state. Inhibitors, R-pSer-Psi[CH(2)N]-Pro-2-(indol-3 yl)ethylamine, 1 [R = fluorenylmethoxycarbonyl (Fmoc)] and 2 (R = Ac), of Pin1 were synthesized and bioassayed. Inhibitor 1 had an IC(50) value of 6.3 MUM, which is 4.5-fold better for Pin1 than our comparable ground-state analogue, a cis-amide alkene isostere-containing inhibitor. The change of Fmoc to Ac in 2 improved aqueous solubility for structural determination and resulted in an IC(50) value of 12 MUM. The X-ray structure of the complex of 2 bound to Pin1 was determined to 1.76 A resolution. The structure revealed that the reduced amide adopted a conformation similar to the proposed twisted-amide transition state of Pin1, with a trans-pyrrolidine conformation of the prolyl ring. A similar conformation of substrate would be destabilized relative to the planar amide conformation. Three additional reduced amides, with Thr replacing Ser and l- or d pipecolate (Pip) replacing Pro, were slightly weaker inhibitors of Pin1. PMID- 21980918 TI - Total synthesis of gelsemoxonine. AB - The first total synthesis of gelsemoxonine (1) has been accomplished. Divinylcyclopropane-cycloheptadiene rearrangement of the highly functionalized substrate was successfully applied to assemble the spiro-quaternary carbon center connected to the bicyclic seven-membered core structure. A one-pot isomerization reaction of the alpha,beta-unsaturated aldehyde to the saturated ester via the TMSCN-DBU reagent combination allowed a facile diastereoselective introduction of the latent nitrogen functionality of the unique azetidine moiety. PMID- 21980917 TI - 57Fe ENDOR spectroscopy and 'electron inventory' analysis of the nitrogenase E4 intermediate suggest the metal-ion core of FeMo-cofactor cycles through only one redox couple. AB - N(2) binds to the active-site metal cluster in the nitrogenase MoFe protein, the FeMo-cofactor ([7Fe-9S-Mo-homocitrate-X]; FeMo-co) only after the MoFe protein has accumulated three or four electrons/protons (E(3) or E(4) states), with the E(4) state being optimally activated. Here we study the FeMo-co (57)Fe atoms of E(4) trapped with the alpha-70(Val->Ile) MoFe protein variant through use of advanced ENDOR methods: 'random-hop' Davies pulsed 35 GHz ENDOR; difference triple resonance; the recently developed Pulse-Endor-SaTuration and REcovery (PESTRE) protocol for determining hyperfine-coupling signs; and Raw-DATA (RD) PESTRE, a PESTRE variant that gives a continuous sign readout over a selected radiofrequency range. These methods have allowed experimental determination of the signed isotropic (57)Fe hyperfine couplings for five of the seven iron sites of the reductively activated E(4) FeMo-co, and given the magnitude of the coupling for a sixth. When supplemented by the use of sum-rules developed to describe electron-spin coupling in FeS proteins, these (57)Fe measurements yield both the magnitude and signs of the isotropic couplings for the complete set of seven Fe sites of FeMo-co in E(4). In light of the previous findings that FeMo-co of E(4) binds two hydrides in the form of (Fe-(MU-H(-))-Fe) fragments, and that molybdenum has not become reduced, an 'electron inventory' analysis assigns the formal redox level of FeMo-co metal ions in E(4) to that of the resting state (M(N)), with the four accumulated electrons residing on the two Fe-bound hydrides. Comparisons with earlier (57)Fe ENDOR studies and electron inventory analyses of the bio-organometallic intermediate formed during the reduction of alkynes and the CO-inhibited forms of nitrogenase (hi-CO and lo-CO) inspire the conjecture that throughout the eight-electron reduction of N(2) plus 2H(+) to two NH(3) plus H(2), the inorganic core of FeMo-co cycles through only a single redox couple connecting two formal redox levels: those associated with the resting state, M(N), and with the one-electron reduced state, M(R). We further note that this conjecture might apply to other complex FeS enzymes. PMID- 21980919 TI - Compositional changes in 'Bartlett' pear ( Pyrus communis L.) cell wall polysaccharides as affected by sunlight conditions. AB - Preharvest conditions can have a great impact on fruit quality attributes and postharvest responses. Firmness is an important quality attribute in pear, and excessive softening increases susceptibility to bruising and decay, thus limiting fruit postharvest life. Textural characteristics of fruits are determined at least in part by cell wall structure and disassembly. Few studies have analyzed the influence of fruit preharvest environment in softening, cell wall composition, and degradation. In the current work 'Bartlett' pears grown either facing the sun (S) or in the shade (H) were harvested and stored for 13 days at 20 degrees C. An evaluation of fruit soluble solids, acidity, color, starch degradation, firmness, cell wall yield, pectin and matrix glycan solubilization, depolymerization, and monosaccharide composition was carried out. Sun-exposed pears showed more advanced color development and similar levels of starch degradation, sugars, and acids than shaded fruit. Sunlight-grown pears were at harvest firmer than shade-grown pears. Both fruit groups softened during storage at 20 degrees C, but even after ripening, sun-exposed pears remained firmer. Sunlight exposure did not have a great impact on pectin molecular weight. Instead, at harvest a higher proportion of water-solubilized uronic acids and alkali-solubilized neutral sugars and a larger mean molecular size of tightly bound glycans was found in sun-exposed pears. During ripening cell wall catabolism took place in both sun- and shade-grown pears, but pectin solubilization was clearly delayed in sun-exposed fruit. This was associated with decreased removal of RG I-arabinan side chains rather than with reduced depolymerization. PMID- 21980920 TI - Directed evolution of a temperature-, peroxide- and alkaline pH-tolerant versatile peroxidase. AB - The VPs (versatile peroxidases) secreted by white-rot fungi are involved in the natural decay of lignin. In the present study, a fusion gene containing the VP from Pleurotus eryngii was subjected to six rounds of directed evolution, achieving a level of secretion in Saccharomyces cerevisiae (21 mg/l) as yet unseen for any ligninolytic peroxidase. The evolved variant for expression harboured four mutations and increased its total VP activity 129-fold. The signal leader processing by the STE13 protease at the Golgi compartment changed as a consequence of overexpression, retaining the additional N-terminal sequence Glu Ala-Glu-Ala that enhanced secretion. The engineered N-terminally truncated variant displayed similar biochemical properties to those of the non-truncated counterpart in terms of kinetics, stability and spectroscopic features. Additional cycles of evolution raised the T50 8 degrees C and significantly increased the enzyme's stability at alkaline pHs. In addition, the Km for H2O2 was enhanced up to 15-fold while the catalytic efficiency was maintained, and there was an improvement in peroxide stability (with half-lives for H2O2 of 43 min at a H2O2/enzyme molar ratio of 4000:1). Overall, the directed evolution approach described provides a set of strategies for selecting VPs with improvements in secretion, activity and stability. PMID- 21980921 TI - Best practice for peripheral blood progenitor cell mobilization and collection in adults and children: results of a Societa Italiana Di Emaferesi e Manipolazione Cellulare (SIDEM) and Gruppo Italiano Trapianto Midollo Osseo (GITMO) consensus process. AB - BACKGROUND: A large heterogeneity in current mobilization and collection practices is perceived. Moreover, recent evidence introduced novel issues into some specific topics. Optimization of the clinical practice, through the adoption of clinical practice guidelines, previously proved to reduce health care resource use. STUDY DESIGN AND METHODS: Two Italian scientific societies, Societa Italiana Di Emaferesi e Manipolazione Cellulare (SIDEM) and Gruppo Italiano Trapianto Midollo Osseo (GITMO), perceived the need of hematologists and transfusionists to share a common paradigm in the setting of hematopoietic stem cell transplantation (SCT). The aim of the current position paper is to provide common definitions and criteria for mobilization and collection of peripheral blood stem cells both in autologous and in the allogeneic setting. Current international and national standards (i.e., International Society of Hematotherapy and Graft Engineering) and recommendations (i.e., European Group for Blood and Marrow Transplantation) were harmonized with the Panel recommendations. RESULTS: The Expert Panel consisted of nine members (five transfusionists and four hematologists with both clinical and scientific experience of SCT in both pediatric and adult setting) and one methodologist and first convened on April 19, 2010: they in turn agreed on the questions to be answered by the project. Available literature was reviewed by one expert and the methodologist and presented to the other members. Statements were then formulated. SIDEM and GITMO planned an informal meeting of the Panel every 2 years to discuss relevant updates and possible changes to the recommendations. CONCLUSION: The efforts of the expert panel members allowed to set up and share a common approach to the mobilization, enumeration, and collection issues in the field of both autologous and allogeneic peripheral blood SCT. PMID- 21980922 TI - Versatile and efficient genome editing in human cells by combining zinc-finger nucleases with adeno-associated viral vectors. AB - Zinc-finger nucleases (ZFNs) have become a valuable tool for targeted genome engineering. Based on the enzyme's ability to create a site-specific DNA double strand break, ZFNs promote genome editing by activating the cellular DNA damage response, including homology-directed repair (HDR) and nonhomologous end-joining. The goal of this study was (i) to demonstrate the versatility of combining the ZFN technology with a vector platform based on adeno-associated virus (AAV), and (ii) to assess the toxicity evoked by this platform. To this end, human cell lines that harbor enhanced green fluorescence protein (EGFP) reporters were generated to easily quantify the frequencies of gene deletion, gene disruption, and gene correction. We demonstrated that ZFN-encoding AAV expression vectors can be employed to induce large chromosomal deletions or to disrupt genes in up to 32% of transduced cells. In combination with AAV vectors that served as HDR donors, the AAV-ZFN platform was utilized to correct a mutation in EGFP in up to 6% of cells. Genome editing on the DNA level was confirmed by genotyping. Although cell cycle profiling revealed a modest G2/M arrest at high AAV-ZFN vector doses, platform-induced apoptosis could not be detected. In conclusion, the combined AAV-ZFN vector technology is a useful tool to edit the human genome with high efficiency. Because AAV vectors can transduce many cell types relevant for gene therapy, the ex vivo and in vivo delivery of ZFNs via AAV vectors will be of great interest for the treatment of inherited disorders. PMID- 21980923 TI - Evaluation of efficacy and safety of finasteride 1 mg in 3177 Japanese men with androgenetic alopecia. AB - Before now, there has been no study of finasteride use exceeding 1 year in Japanese men with androgenetic alopecia (AGA) except the study subsequently conducted from the development phase. Since the launch of finasteride, no study in a larger population had been reported. Ethnic variation of the onset age, progressive nature and degree of hair loss of androgenetic alopecia are known. The therapeutic effect of oral finasteride (Propecia) was examined on androgenetic alopecia of Japanese men. The efficacy and safety of finasteride (1 mg tablet) was evaluated in Japanese men with AGA in the long term. The study enrolled 3177 men given finasteride 1 mg/day from January 2006 to June 2009 at our clinic. Efficacy was evaluated in 2561 men by the modified global photographic assessment; the photographs were assessed using the standardized 7 point rating scale. Safety data were assessed by interviews and laboratory tests in all men enrolled in the study. The overall effect of hair growth was seen in 2230 of 2561 men (87.1%), in whom hair greatly (11.1%), moderately (36.5%) and slightly (39.5%) increased. The response rate improved with increasing duration of treatment. Adverse reactions occurred in 0.7% (23/3177) of men; seven men discontinued treatment based on risk-benefit considerations. No specific safety problems associated with long-term use were observed. This study represents data collected at a single institution. Many patients did not receive follow-up examination. In Japanese men with AGA, oral finasteride used in the long-term study maintained progressive hair regrowth without recognized side-effect. PMID- 21980924 TI - BDNF Val66Met and cognition: all, none, or some? A meta-analysis of the genetic association. AB - The Val66Met, G196A (rs6265) polymorphism in the brain-derived neurotrophic factor gene, BDNF, located at 11p13, has been associated with a wide range of cognitive functions. Yet, the pattern of results is complex and conflicting. In this study, we conducted a meta-analysis that included 23 publications containing 31 independent samples comprised of 7095 individuals. The phenotypes that were examined in this analysis covered a wide variety of cognitive functions and included indicators of general cognitive ability, memory, executive function, visual processing skills and cognitive fluency. The meta-analysis did not establish significant genetic associations between the Val66Met polymorphism and any of the phenotypes that were included. PMID- 21980925 TI - Microneedle assisted iontophoretic transdermal delivery of prochlorperazine edisylate. AB - This paper investigates the microneedle (MN) mediated in vitro transdermal iontophoretic delivery of prochlorperazine edisylate (PE) across dermatomed human skin. The DermarollerTM induced microchannels were visualized using methylene blue staining and scanning electron microscopy. In vitro skin permeation studies were performed using vertical static Franz diffusion cells. Iontophoretic protocols involved application of direct current at a density of 0.4 mA/cm(2) using Ag as an anode and Ag/AgCl as a cathode. The effect of PE concentration (20, 50 and 100 mg/mL), number of passes of microneedles (0, 5, 10 and 20) on both iontophoretic and passive delivery of PE was studied. The Dermarollertm was found to successfully breach the skin barrier and a linear relationship (r(2) = 0.99) was observed between the number of passes of the DermarollerTM and the number of microchannels created. Passive transdermal flux of PE (0.060 +/- 0.003 ug/cm(2)/h) at 50 mg/mL donor PE concentration) was low and increased (4.15 +/- 0.57 ug/cm(2)/h) with the application of direct current. Application of iontophoresis in conjunction with microneedle pre-treatment resulted in enhanced flux (4.90 +/- 0.39 ug/cm(2)/h at 50 mg/mL donor PE concentration) of PE. The projected transdermal PE flux indicates that a 9 cm(2) patch could deliver PE in a sufficient amount to maintain therapeutic levels of the drug. In conclusion, microneedles when used in conjunction with iontophoresis significantly enhanced the transdermal delivery of PE and it may be feasible to develop an iontophoretic transdermal patch that could be integrated with MN. PMID- 21980927 TI - Effect of low and chronic radiation exposure: a case-control study of mental retardation and cleft lip/palate in the monazite-bearing coastal areas of southern Kerala. AB - A population-based 1:3 age-matched case-control study was conducted during 2006 2009 to assess the role of high-level natural radiation (>1 mSv/year) on congenital mental retardation and cleft lip/palate in the southwest coastal area of Kerala. Dosimetry was carried out in the house where parents resided during conception and the subsequent two trimesters of pregnancy of the study subject. Conditional logistic regression did not suggest any statistically significant association of either mental retardation (n = 445) or cleft lip/palate (n = 116) with high-level natural radiation. The odds of mental retardation and cleft lip/palate among those exposed to high-level natural radiation relative to normal levels of natural background radiation (<=1 mSv/year) were 1.26 (95% CI: 0.91 1.73) and 0.56 (95% CI: 0.31-1.02), respectively, after controlling for gender and maternal age at birth of the study subject. The data did not suggest any dose related trend in the risk of either mental retardation (P = 0.113) or cleft lip/palate (P = 0.908). Notwithstanding the use of a single dose estimate to reconstruct past radiation exposure and the complex etiology of congenital malformations, it may reasonably be concluded that the prevailing high-level natural radiation in the study area does not appear to increase the risk of either mental retardation or cleft lip/palate among offspring of parents staying in the area. PMID- 21980928 TI - ANZJP this month. PMID- 21980929 TI - Recruitment into psychiatry: an international challenge. PMID- 21980926 TI - The potential role of Aurora kinase inhibitors in haematological malignancies. AB - Aurora kinases play an important role in the control of the cell cycle and have been implicated in tumourigenesis in a number of cancers. Among the haematological malignancies, overexpression of Aurora kinases has been reported in acute myeloid leukaemia, chronic myeloid leukaemia, acute lymphoblastic leukaemia, multiple myeloma, aggressive non-Hodgkin lymphoma and Hodgkin lymphoma. A large number of Aurora kinase inhibitors are currently in different stages of clinical development. In addition to varying in their selectivity for the different Aurora kinases, some also have activity directed at other cellular kinases involved in important molecular pathways in cancer cells. This review summarizes the biology of Aurora kinases and discusses why they may be good therapeutic targets in different haematological cancers. We describe preclinical data that has served as the rationale for investigating Aurora kinase inhibitors in different haematological malignancies, and summarize published results from early phase clinical trials. While the anti-tumour effects of Aurora kinase inhibitors appear promising, we highlight important issues for future clinical research and suggest that the optimal use of these inhibitors is likely to be in combination with cytotoxic agents already in use for the treatment of various haematological cancers. PMID- 21980930 TI - Australia's Better Access initiative: still awaiting serious evaluation? PMID- 21980931 TI - Clinical guidelines for the physical care of mental health consumers: a comprehensive assessment and monitoring package for mental health and primary care clinicians. AB - OBJECTIVES: People with a mental illness are more likely to experience poor physical health as compared to the general population. Currently, Australian mental health patients experience a relatively low level of physical health appraisal, prompting the development of the Clinical guidelines for the physical care of mental health consumers assessment and monitoring package. METHOD: The Clinical guidelines package takes an holistic approach, with a focus on the key dimensions of medication effects, lifestyle, existing or developing physical disorders, alcohol and illicit drug use, and psychosocial factors. RESULTS: The package consists of a metabolic syndrome algorithm wall chart, a Clinician handbook, a Psychosocial assessment booklet, and a set of three screening forms. CONCLUSIONS: By taking a user-friendly, flexible, evidence-based approach, the resource can be used by all clinicians involved in the healthcare of people with a mental illness. PMID- 21980932 TI - Movement disorder as prodrome of schizophrenia. PMID- 21980933 TI - Critical role of organic anion transporters 1 and 3 in kidney accumulation and toxicity of aristolochic acid I. AB - Ingestion of aristolochic acid (AA), especially its major constituent aristolochic acid I (AAI), results in severe kidney injury known as aristolochic acid nephropathy (AAN). Although hepatic cytochrome P450s metabolize AAI to reduce its kidney toxicity in mice, the mechanism by which AAI is uptaken by renal cells to induce renal toxicity is largely unknown. In this study, we found that organic anion transporters (OATs) 1 and 3, proteins known to transport drugs from the blood into the tubular epithelium, are responsible for the transportation of AAI into renal tubular cells and the subsequent nephrotoxicity. AAI uptake in HEK 293 cells stably transfected with human OAT1 or OAT3 was greatly increased compared to that in the control cells, and this uptake was dependent on the AAI concentration. Administration of probenecid, a well-known OAT inhibitor, to the mice reduced AAI renal accumulation and its urinary excretion and protected mice from AAI-induced acute tubular necrosis. Further, AAI renal accumulation and severe kidney lesions induced by AAl in Oat1 and Oat3 gene knockout mice all were markedly suppressed compared to those in the wild type mice. Together, our results suggest that OAT1 and OAT3 have a critical role in AAl renal accumulation and toxicity. These transporters may serve as a potential therapeutic target against AAN. PMID- 21980935 TI - RNA-mediated gene silencing of ToxB in Pyrenophora tritici-repentis. AB - The fungus Pyrenophora tritici-repentis causes tan spot, a wheat leaf disease of worldwide importance. The pathogen produces three host-selective toxins, including Ptr ToxB, which causes chlorophyll degradation and foliar chlorosis on toxin-sensitive wheat genotypes. The ToxB gene, which codes for Ptr ToxB, was silenced in a wild-type race 5 isolate of the fungus thorough a sense- and antisense-mediated silencing mechanism. Toxin production by the silenced strains was evaluated in culture filtrates of the fungus via Western blotting analysis, and plant bioassays were conducted to test the virulence of the transformants in planta. The chlorosis-inducing ability of the silenced strains was correlated with the quantity of Ptr ToxB, and transformants in which toxin production was strongly decreased also caused very little disease on toxin-sensitive wheat genotypes. Cytological analysis of the infection process revealed that, in addition to a reduced capacity to induce chlorosis, the silenced strains with the greatest decrease in the levels of Ptr ToxB produced significantly fewer appressoria than the wild-type isolate, 12 and 24 h after inoculation onto wheat leaves. The results provide strong support for the suggestion that the amount of Ptr ToxB protein produced by fungal isolates plays a significant role in the quantitative variation in the virulence of P. tritici-repentis. PMID- 21980934 TI - Increasing long-term safety of seasonal grass pollen sublingual immunotherapy: the ECRIT study. AB - OBJECTIVE: The usual build-up phase of days or weeks in allergen-specific immunotherapy entails inconveniences for individuals with symptoms only during the pollen season. Additionally, affected individuals often appear for treatment shortly before the expected start of the season without enough time for titration. This double-blind, placebo-controlled study evaluated the safety of ultra-rush grass pollen immunotherapy with sublingual drops (Staloral)(r) in co seasonal treatment over three consecutive seasons. METHODS: 209 patients with grass pollen allergic rhinitis received ultra-rush titration (30, 90, 150 and 300 index of reactivity (IR)) of a five grass pollen mixture or placebo every 20 min at the start of the season, followed by 300 IR daily or placebo until the end of the respective season for three consecutive years. Adverse events were documented. RESULTS: Mean treatment duration varied between seasons (81.8 - 92.7 days). No systemic or anaphylactic reactions were reported and no unexpected adverse events were observed. Adverse events included application site irritation, oedema, abdominal pain and diarrhoea. Fourteen patients discontinued treatment due to adverse events (placebo: four (6%) patients, verum: ten (7%) patients). Adverse events decreased in frequency over each consecutive year of treatment. CONCLUSION: Seasonal sublingual immunotherapy with ultra-rush titration is well tolerated even when administered as co-seasonal treatment. It may be a valuable option for patients who present late. PMID- 21980936 TI - Evolution of anterior segment reconstruction after live donor adult liver transplantation: a single-center experience. AB - Controversy exists regarding the best method for venous outflow reconstruction after live donor liver transplantation using right lobe grafts. Some authors advocate routine inclusion of the middle hepatic vein with the graft, whereas others favor a more selective approach. In this report, we examine the evolution of our decision making and technique of selective anterior venous segment reconstruction during live donor adult liver transplantation performed in 226 recipients. We have developed a simplified back-bench procedure using sequential composite anastomosis using various vascular conduits with syndactylization to the right hepatic vein creating a single large-outflow anastomosis in the recipient. Conduits used include iliac artery or vein allograft, recanalized umbilical vein, cryopreserved iliac artery allograft, and 6-mm synthetic expanded polytetrafluoroethylene vascular graft. This technique can be performed quickly, safely, and under cold storage conditions and results in excellent outcome while minimizing donor risk. PMID- 21980938 TI - Fumes from the cupboard. PMID- 21980939 TI - Long-term behavioural consequences of infant feeding: the limits of observational studies. AB - Observational (non-experimental) studies of the association between infant feeding and subsequent child or adult behaviour are prone to residual confounding by subtle differences in psychological attributes and interactional styles of mothers who breast feed vs. those who formula-feed. We followed up 13,889 6.5 year-old Belarusian children who participated in a large cluster-randomised trial of a breast-feeding promotion intervention. Behaviour was evaluated using the Strengths and Difficulties Questionnaire (SDQ), completed independently by the children's parents and teachers. We compared the results of experimental (intention-to-treat, ITT) and observational analyses (based on feeding actually received), both adjusted for clustering. Observational analyses were additionally adjusted for geographical region, urban vs. rural residence, child's sex, age at follow-up, birthweight, and maternal and paternal education. No differences between the randomised experimental vs. control groups were observed in ITT analyses. In contrast, small but statistically significant associations with weaning prior to 3 months were observed for parent and teacher SDQ scores on total difficulties, conduct problems and hyperactivity, even after multivariable adjustment. The absence of associations based on ITT analyses, in contrast with the significant associations based on observed breast-feeding duration, strongly suggests that the latter are biased by residual confounding. PMID- 21980940 TI - Systematic review and meta-analysis investigating breast feeding and childhood wheezing illness. AB - There is conflicting evidence concerning the relationship between breast feeding and wheezing illness. The objective of this study was to investigate whether there is any association between breast feeding and wheezing in children aged over 5 years and to discover possible sources of heterogeneity. An electronic search of MEDLINE and EMBASE databases was conducted from January 2000 to June 2010. In addition, reference lists from relevant publications were searched. Birth cohort, cross-sectional and case-control studies were included if they measured any breast feeding or exclusive breast feeding for 3 or 4 months. Wheezing illness, including asthma, was identified based on symptoms, reported diagnosis or objective criteria. Thirty-one publications were identified for meta analysis. There was no association found between any or exclusive breast feeding and wheezing illness, although there was a high level of heterogeneity between the studies. Subgroup analysis revealed that any breast feeding slightly lowers the odds of wheeze (pooled odds ratio 0.92 [0.86, 0.98]) but slightly increases the odds of asthma defined by specific criteria (pooled odds ratio 1.10 [1.00, 1.22]). This meta-analysis does not provide evidence that breast feeding is protective against wheezing illness in children aged 5 years and over. The difference in the effects of breast feeding according to the nature of the wheezing illness highlights the importance of the heterogeneity of illness phenotypes. PMID- 21980941 TI - Duration of breast feeding and risk of developmental delay in Taiwanese children: a nationwide birth cohort study. AB - The purpose of this study was to examine the relationship between duration of breast feeding and four developmental domains: gross motor, fine motor, language, and personal/social skills. This study included 14,621 infants from birth to 18 months of age. In the Taiwan Birth Cohort Study, four developmental screening items adapted from the Denver Development Screening Test were most appropriate for children aged 15 to 18 months. The proportion of young children who had mastered specific milestones increased consistently with longer duration of breast feeding. The adjusted odds ratios of the risk of developmental delay for the longest duration of breast feeding vs. never breast-fed were 0.69 [95% confidence interval (CI) 0.57, 0.83] for gross motor, 0.64 [95% CI 0.53, 0.77] for fine motor, 0.74 [95% CI 0.60, 0.91] for language, and 0.76 [95% CI 0.64, 0.90] for personal/social skills. Regardless of when the mothers returned to work, duration of breast feeding was found to have an inverse association with developmental delay in young children. The protection against developmental delays remained significant for those children who were breast-fed for more than 6 months. Children who were breast-fed for longer than 6 months had a lower risk of developmental delay than those who were never breast-fed. These data support the hypothesis that duration of breast feeding is positively related to young children's neurodevelopment. PMID- 21980942 TI - Refuelling of vehicles, the use of wood burners and the risk of acute lymphoblastic leukaemia in childhood. AB - It is plausible that exposure of the parents before birth or of the child to sources of benzene increases the risk of childhood acute lymphoblastic leukaemia (ALL). The aim of this analysis was to investigate whether refuelling a vehicle with petrol before birth or burning wood to heat the home before or after the child's birth increased the risk of childhood ALL. Data from 389 cases and 876 frequency-matched controls were analysed using unconditional logistic regression, adjusting for study matching factors and potential confounders. The odds ratio (OR) for the mother ever refuelling a vehicle with petrol for non-occupational purposes before or during the pregnancy was 0.97 [95% confidence interval (CI) 0.69, 1.38]. The OR for the father for this exposure in the year before conception was 0.88 [95% CI 0.52, 1.48]. The OR for use of a closed wood burner to heat the home in the year before or during pregnancy was 1.41 [95% CI 1.02, 1.94] and 1.25 [95% CI 0.92, 1.70] after birth. We found no evidence that non occupational refuelling a vehicle with petrol in the year before or during pregnancy increased the risk of ALL in the offspring. There was weak evidence that burning wood in a closed burner to heat the home increased the risk, but there was no dose-response relationship and chance could explain the finding. PMID- 21980943 TI - Self-report versus medical record - perinatal factors in a study of infant leukaemia: a study from the Children's Oncology Group. AB - In a case-control study of infant leukaemia, we assessed agreement between medical records and mother's self-reported pregnancy-related conditions and procedures and infant treatments. Interview and medical record data were available for 234 case and 215 control mothers. Sensitivity, specificity and predictive values for maternal report were estimated for case and control mothers separately, taking the medical record as correct. For most perinatal conditions, sensitivity and specificity were over 75%. Low sensitivity was observed for maternal protein or albumin in the urine (cases: 12% [95% exact confidence interval (CI) 8%, 18%]; controls: 11% [95% CI 7%, 17%]) and infant supplemental oxygen use (cases: 25% [95% CI 11%, 43%]; controls: 24% [95% CI 13%, 37%]). Low specificity was found for peripheral oedema (cases: 47% [95% CI 37%, 58%]; controls: 54% [95% CI 43%, 64%]). Sensitivity for maternal hypertension appeared much lower for cases (cases: 46% [95% CI 28%, 66%]; controls: 90% [95% CI 70%, 99%]; P = 0.003). We did not detect other case-control differences in recall (differentiality), even though the average time between childbirth and interview was 2.7 years for case and 3.7 years for control mothers. Many conditions exhibited notable differences between interview and records. We recommend use of multiple measurement sources to allow both cross-checking and synthesis of results into more accurate measures. PMID- 21980944 TI - Feasibility of neonatal dried blood spot retrieval amid evolving state policies (2009-2010): a Children's Oncology Group study. AB - Dried blood spots (DBS) are collected uniformly from US newborns to test for metabolic and other disorders. Because evidence exists for prenatal origins of some diseases, DBS may provide unique prenatal exposure records. Some states retain residual DBS and permit their use in aetiological studies. The primary study aim was to assess the feasibility of obtaining residual DBS from state newborn screening programmes for paediatric and adolescent cancer patients nationwide with parental/subject consent/assent. Families of leukaemia and lymphoma patients aged <=21 years diagnosed from 1998 to 2007 at randomly selected Children's Oncology Group institutions across the US were questioned (n = 947). Parents/guardians and patients aged >=18 years were asked to release DBS to investigators in spring 2009. DBS were then requested from states. Overall, 299 families (32%) released DBS. Consenting/assenting patients were born in 39 US states and 46 DBS were obtained from five states; 124 DBS were unobtainable because patients were born prior to dates of state retention. State policies are rapidly evolving and there is ongoing discussion regarding DBS storage and secondary research uses. Currently, population-based DBS studies can be conducted in a limited number of states; fortunately, many have large populations to provide reasonably sized paediatric subject groups. PMID- 21980946 TI - Stressful events, smoking exposure and other maternal risk factors associated with gestational diabetes mellitus. AB - The incidence of gestational diabetes mellitus (GDM) has increased significantly in the last few decades in the US. Understanding its risk factors is imperative for the prevention of GDM and its sequelae, but the roles of behavioural risk factors such as stressful events and smoking on GDM are generally not well understood. Using data obtained from the New York State (NYS) Pregnancy Risk Assessment Monitoring System survey for 2004-06 and the NYS birth certificates, we examined relationships between GDM, stressful events and smoking among 2690 women who had live singleton births and did not have pre-pregnancy diabetes. After adjustment for risk factors such as maternal age, race/ethnicity, pre pregnancy body mass index, hypertension, as well as smoking exposure, education, parity, and gestation at first visit for prenatal care, we found that having five or more stressful events 12 months before the baby was born was significantly associated with GDM (OR = 2.49, [95% CI 1.49, 4.16]). In another model, having any stressful event(s) other than 'moved to a new address' 12 months before the baby was born was also moderately associated with GDM (OR = 1.38, [95% CI 1.04, 1.85]). Smoking exposure, assessed by combining maternal smoking and second-hand smoke exposure into six levels, had no significant association with GDM, and did not show a dose-response pattern. The present study suggests that stressful events during pregnancy may be an independent risk factor for GDM. Future studies of GDM should include this common, but potentially modifiable risk factor in analyses. PMID- 21980945 TI - Maternal prenatal cigarette, alcohol and illicit drug use and risk of infant leukaemia: a report from the Children's Oncology Group. AB - Several case-control studies have evaluated associations between maternal smoking, alcohol consumption and illicit drug use during pregnancy and risk of childhood leukaemia. Few studies have specifically focused on infants (<1 year) with leukaemia, a group that is biologically and clinically distinct from older children. We present data from a Children's Oncology Group case-control study of 443 infants diagnosed with acute leukaemia [including acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML)] between 1996 and 2006 and 324 population controls. Mothers were queried about their cigarette, alcohol and illicit drug use 1 year before and throughout pregnancy. Odds ratios (ORs) and 95% confidence intervals [CI] were calculated using adjusted unconditional logistic regression models. Maternal smoking (>1 cigarette/day) and illicit drug use (any amount) before and/or during pregnancy were not significantly associated with infant leukaemia. Alcohol use (>1 drink/week) during pregnancy was inversely associated with infant leukaemia overall [OR = 0.64; 95% CI 0.43, 0.94], AML [OR = 0.49; 95% CI 0.28, 0.87], and leukaemia with mixed lineage leukaemia gene rearrangements ('MLL+') [OR = 0.59; 95% CI 0.36, 0.97]. While our results agree with the fairly consistent evidence that maternal cigarette smoking is not associated with childhood leukaemia, the data regarding alcohol and illicit drug use are not consistent with prior reports and are difficult to interpret. It is possible that unhealthy maternal behaviours during pregnancy, some of which carry potential legal consequences, may not be adequately measured using only self report. Future case-control studies of childhood leukaemia that pursue these exposures may benefit from incorporation of validated instruments and/or biomarkers when feasible. PMID- 21980947 TI - International migration and gestational diabetes mellitus: a systematic review of the literature and meta-analysis. AB - Influxes of migrant women of childbearing age to receiving countries have made their perinatal health status a key priority for many governments. The international research collaboration Reproductive Outcomes And Migration (ROAM) reviewed published studies to assess whether migrants in countries of resettlement have a greater risk of gestational diabetes mellitus (GDM) than women in receiving countries. A systematic review of the literature from Medline, Embase, PsychInfo and CINAHL from 1990 to 2009 included studies of migrant women and GDM. Studies were excluded if there was no cross-border movement or comparison group or if the receiving country was not the country of resettlement. Studies were assessed for quality, analysed descriptively and meta-analysed. Twenty-four reports (representing >120,000 migrants) met our inclusion criteria. Migrants were described primarily by geographic origin; other relevant aspects (e.g. time in country, language fluency) were rarely studied. Migrants' results for GDM were worse than those for receiving-country women in 79% of all studies. Meta-analyses showed that, compared with receiving-country women, Caribbean, African, European and Northern European women were at greater risk of GDM, while North Africans and North Americans had risks similar to receiving-country women. Although results of the 31 comparisons of Asians, East Africans or non-Australian Oceanians were too heterogeneous to provide a single GDM risk estimate for migrant women, only one comparison was below the receiving-country comparison group, all others presented a higher risk estimate. The majority of women migrants to resettlement countries are at greater risk for GDM than women resident in receiving countries. Research using clear, specific migrant definitions, adjusting for relevant risk factors and including other aspects of migration experiences is needed to confirm and understand these findings. PMID- 21980948 TI - Neonatal mortality due to preterm birth at 28-36 weeks' gestation in China, 2003 2008. AB - Almost all (99%) neonatal deaths occur in developing countries, where the progress in reducing neonatal mortality rates (NMR) has been small; the Millennium Development Goal for child survival cannot be met if this situation continues. China is among the 10 countries that have the largest numbers of neonatal deaths. In order to provide effective interventions to reduce the national NMR for government policy makers, we analyse the trends, causes and characteristics of the neonatal deaths of preterm babies in different regions of China during the period 2003-2008. The data for this retrospective study were retrieved from the population-based Maternal and Child Health Surveillance System of China. The Cochran-Armitage trend test was used to analyse the trend of NMRs due to immaturity. The national NMR due to immaturity has decreased by 38.7% in 6 years. However, the proportion of preterm births among the causes of neonatal death has increased significantly from 33.6% in 2003 to 40.9% in 2008. The relative risk of neonatal death among preterm babies has shown significant regional disparity. In 2008, the adjusted relative risk was 1.30 [95% confidence interval (CI) 0.95, 1.78] in the inland regions and 2.37 [95% CI 1.56, 3.60] in the remote regions, both compared with the coastal regions. The proportion of neonatal deaths with a gestational age <32 weeks or a birthweight <1500 g was highest among the coastal regions. Most neonatal deaths of preterm babies in remote areas were born at home and were not treated before death. Our study suggests that preterm birth is the leading cause of neonatal death in China and neonatal mortality due to immaturity displayed regional differences. The Chinese government should implement major effective strategies for reducing the mortality of preterm infants to further decrease the total NMR. Priority interventions should be region-specific, depending on the availability of economic and health care resources. PMID- 21980949 TI - The role of medicine in the decline of post-War infant mortality in Japan. AB - The infant mortality rate (IMR) in Japan declined dramatically in the immediate post-War period (1947-60) in Japan. We compared the time trends in Growth Domestic Product (GDP) in Japan against declines in IMR. We then conducted a prefecture-level ecological analysis of the rate of decline in IMR and post neonatal mortality from 1947 to 1960, focusing on variations in medical resources and public health strategies. IMR in Japan started to decline after World War II, even before the era of rapid economic growth and the introduction of a universal health insurance system in the 1960s. The mortality rates per 1000 infants in 2009 were 2.38 for IMR, 1.17 for neonatal mortality and 1.21 for post-neonatal mortality. The rate of decline in IMR and preventable IMR (PIMR) during the post War period was strongly correlated with prefectural variations in medical resources (per capita physicians, nurses, and proportion of in-hospital births). The correlation coefficients comparing the number of physicians in 1955 with the declines in IMR and PIMR from 1947 to 1960 were 0.46 [95% confidence interval (CI) 0.19, 0.66] and 0.39 [95% CI 0.11, 0.61], respectively. By contrast, indicators of public health strategies were not associated with IMR decline. The IMR in Japan has been decreasing and seems to be entering a new era characterised by lower neonatal compared with post-neonatal mortality. Furthermore, the post War history of Japan illustrates that improvement in infant mortality is attributable to the influence of medical care, even in the absence of rapid economic development. PMID- 21980950 TI - Photochromic properties of [2.2]paracyclophane-bridged imidazole dimer with increased photosensitivity by introducing pyrenyl moiety. AB - The photochromic [2.2]paracyclophane-bridged imidazole dimers show instantaneous coloration upon exposure to UV light and rapid fading in the dark. A new [2.2]paracyclophane-bridged imidazole dimer, pseudogem-PPI-DPI[2.2]PC, with high photosensitivity to UVA radiation was developed. To enhance the photosensitivity, we introduced pyrenyl moieties to the [2.2]paracyclophane-bridged imidazole dimer. The localized pi-pi* transition of pyrenyl moieties appears in the UVA radiation region by introducing a pyrenyl moietiy on the 4-position of the imidazole rings. The expansion of the pi-electron system also affects the absorption spectrum of the colored species. The broad absorption band of the colored species covers the whole range of visible light region and its absorbance is approximately equal throughout the visible light region. Thus, pseudogem-PPI DPI[2.2]PC shows the photochromic reaction coloring black upon light irradiation and successive fast thermal bleaching following the monoexponential kinetics with a time constant of 12 ms at room temperature. PMID- 21980952 TI - Microwave disinfection: cumulative effect of different power levels on physical properties of denture base resins. AB - PURPOSE: This study evaluated the cumulative effects of different microwave power levels on the physical properties of two poly(methylmethacrylate) (PMMA) denture base resins. MATERIALS AND METHODS: Eight sets of four PMMA specimens each (two polymerized in a water bath and two using microwave energy) were immersed in beakers containing 200 ml of distilled water. Each beaker was subjected to microwave irradiation for 3 minutes at a power level of 450,630, or 900 W. The surface roughness, surface hardness, linear stability, flexural strength, elastic modulus, impact strength, and fractographic properties were evaluated after either 6 or 36 simulated disinfection cycles. The data were statistically analyzed using ANOVA and the Tukey post hoc test (alpha= 0.05). RESULTS: The polymerization method did not influence any property (p > 0.05) except linear stability. The surface roughness (p < 0.001) and hardness (p= 0.011) increased after 36 irradiation cycles at 630 or 900 W. The resin polymerized using microwave energy exhibited greater linear distortion (p= 0.012), and there was a cumulative effect on linear stability for both resins (p < 0.001). No significant change (p > 0.05) was observed in flexural strength; however, the elastic modulus decreased (p= 0.008) after 36 disinfection cycles. The impact strength and crack propagation angles displayed no significant differences (p > 0.05). CONCLUSION: Within the limitations of this study, it can be concluded that microwave disinfection at 450 W to 630 W for 3 minutes is safe for PMMA. PMID- 21980951 TI - The effects of mitochondrial genotype on hypoxic survival and gene expression in a hybrid population of the killifish, Fundulus heteroclitus. AB - The physiological link between oxygen availability and mitochondrial function is well established. However, whether or not fitness variation is associated with mitochondrial genotypes in the field remains a contested topic in evolutionary biology. In this study, we draw on a population of the teleost fish, Fundulus heteroclitus, where functionally distinct subspecies hybridize, likely as a result of past glacial events. We had two specific aims: (i) to determine the effect of mtDNA genotype on survivorship of male and female fish under hypoxic stress and (ii) to determine the effect of hypoxic stress, sex and mtDNA genotype on gene expression. We found an unexpected and highly significant effect of sex on survivorship under hypoxic conditions, but no significant effect of mtDNA genotype. Gene expression analyses revealed hundreds of transcripts differentially regulated by sex and hypoxia. Mitochondrial transcripts and other predicted pathways were among those influenced by hypoxic stress, and a transcript corresponding to the mtDNA control region was the most highly suppressed transcript under the conditions of hypoxia. An RT-PCR experiment on the control region was consistent with microarray results. Effects of mtDNA sequence variation on genome expression were limited; however, a potentially important epistasis between mtDNA sequence and expression of a nuclear-encoded mitochondrial translation protein was discovered. Overall, these results confirm that mitochondrial regulation is a major component of hypoxia tolerance and further suggest that purifying selection has been the predominant selective force on mitochondrial genomes in these two subspecies. PMID- 21980953 TI - Enterobactin is required for biofilm development in reduced-genome Escherichia coli. AB - A variety of bacterial cell surface structures and quorum signalling molecules play a role in biofilm development in Escherichia coli. However, here we show that an engineered reduced-genome E. coli mutant that lacks 17.6% of the parental E. coli genome, including the genes involved in the synthesis of various cell surface structures, such as type 1 fimbriae, curli, exopolysaccharide polymers and the autoinducer-2 signalling molecule, is able to develop mature biofilms. Using temporal gene expression profiling, we investigated phenotypic changes in reduced-genome biofilms in relation with the genes encoding the synthesis of different amino acids that were differentially expressed during biofilm formation. We identified and characterized entB, marR, dosC, mcbR and yahK genes, as involved in biofilm formation by the reduced-genome E. coli. Of these, for a first time, we demonstrated that overproduction of entB and yahK, which encode an enterobactin for iron transport and a hypothetical oxidoreductase protein, respectively, promoted biofilm development and maturation. Our results indicate that specific types of genes contribute to phenotypic changes in reduced-genome E. coli biofilms. In addition, this work demonstrates that the functions of biofilm-specific genes could be analysed through experiments using the reduced genome E. coli. PMID- 21980954 TI - AWP1/ZFAND6 functions in Pex5 export by interacting with cys-monoubiquitinated Pex5 and Pex6 AAA ATPase. AB - During biogenesis of the peroxisome, a subcellular organelle, the peroxisomal targeting signal 1 (PTS1) receptor Pex5 functions as a shuttling receptor for PTS1-containing peroxisomal matrix proteins. However, the precise mechanism of receptor shuttling between peroxisomes and cytosol remains elusive despite the identification of numerous peroxins involved in this process. Herein, a new factor was isolated by a combination of biochemical fractionation and an in vitro Pex5 export assay, and was identified as AWP1/ZFAND6, a ubiquitin-binding NF kappaB modulator. In the in vitro Pex5 export assay, recombinant AWP1 stimulated Pex5 export and an anti-AWP1 antibody interfered with Pex5 export. AWP1 interacted with Pex6 AAA ATPase, but not with Pex1-Pex6 complexes. Preferential binding of AWP1 to the cysteine-ubiquitinated form of Pex5 rather than to unmodified Pex5 was mediated by the AWP1 A20 zinc-finger domain. Inhibition of AWP1 by RNA interference had a significant effect on PTS1-protein import into peroxisomes. Furthermore, in AWP1 knock-down cells, Pex5 stability was decreased, similar to fibroblasts from patients defective in Pex1, Pex6 and Pex26, all of which are required for Pex5 export. Taken together, these results identify AWP1 as a novel cofactor of Pex6 involved in the regulation of Pex5 export during peroxisome biogenesis. PMID- 21980955 TI - Bak Foong Pills induce an analgesic effect by inhibiting nociception via the somatostatin pathway in mice. AB - Dysmenorrhoea, defined as cramping pain in the lower abdomen occurring before or during menstruation, affects, to varying degrees, up to 90% of women of child bearing age. We investigated whether BFP (Bak Foong Pills), a traditional Chinese medicine treatment for dysmenorrhoea, possesses analgesic properties. Results showed that BFP was able to significantly reduce pain responses following subchronic treatment for 3 days, but not following acute (1 h) treatment in response to acetic acid-induced writhing in C57/B6 mice. The analgesic effect was not due to inhibition of COX (cyclo-oxygenase) activity, evidenced by the lack of inhibition of prostacyclin and PGE2 (prostaglandin E2) production. Molecular analysis revealed that BFP treatment modulated the expression of a number of genes in the spinal cord of mice subjected to acetic acid writhing. RT-PCR (reverse transcription-PCR) analysis of spinal cord samples showed that both sst4 (somatostatin receptor 4) and sst2 receptor mRNA, but not MUOR (MU-opiate receptor) and NK1 (neurokinin-1) receptor mRNA, were down-regulated following BFP treatment, thus implicating somatostatin involvement in BFP-induced analgesia. Administration of c-som (cyclo-somatostatin), a somatostatin antagonist, prior to acetic acid-induced writhing inhibited the analgesic effect. Thus subchronic treatment with BFP has anti-nociceptive qualities mediated via the somatostatin pathway. PMID- 21980956 TI - Overview of alemtuzumab therapy for the treatment of T-cell lymphomas. AB - Alemtuzumab is a humanized monoclonal antibody that recognizes the CD52 antigen expressed on malignant and normal B lymphocytes. It has come to be used therapeutically in B-cell malignancies and, in addition, it shows interesting activity also in T-cell lymphomas. Published literature and abstract proceedings were scanned, and a systematic review of phase II studies administering alemtuzumab in patients with T-cell lymphomas was performed. Alemtuzumab is an effective alternative option for patients with peripheral T-cell lymphomas and cutaneous T-cell lymphomas. Alemtuzumab may belong to the current standard of care for nodal and cutaneous T-cell lymphomas. PMID- 21980957 TI - Secondary T-lymphoblastic leukemia in a patient with hairy cell leukemia following cladribine therapy: report of an extremely rare case and review of the literature. PMID- 21980958 TI - Tumor blood vessel "normalization" improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer. AB - We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer. Blood vessel normalization was induced by two doses of thalidomide in tumor-bearing hamsters on 2 consecutive days. All studies in thalidomide-treated animals were performed 48 h after the first dose of thalidomide, previously established as the window of normalization. Biodistribution studies were performed with BPA at a dose of 15.5 mg (10)B/kg in thalidomide-treated (Th+) and untreated (Th-) tumor bearing hamsters. The effect of blood vessel normalization prior to BPA administration on the efficacy of BNCT was assessed in in vivo BNCT studies at the RA-3 Nuclear Reactor in tumor-bearing hamsters. Group I was treated with BPA BNCT after treatment with thalidomide (Th+ BPA-BNCT). Group II was treated with BPA-BNCT alone (Th- BPA-BNCT). Group III was treated with the beam only after treatment with thalidomide (Th+ BO), and Group IV was treated with the beam only (Th- BO). Groups I and II were given the same dose of BPA (15.5 mg (10)B/kg), and all groups (I-IV) were exposed to the same neutron fluence. Two additional groups were treated with the beam only at a higher dose to exacerbate mucositis in precancerous tissue and to explore the potential direct protective effect of thalidomide on radiation-induced mucositis in a scenario of more severe toxicity, i.e. Group V (Th+ hdBO) and Group VI (Th- hdBO). The animals were followed for 28 days. Biodistribution studies revealed no statistically significant differences in gross boron content between Th+ and Th- animals. Overall tumor control (complete response + partial response) at 28 days post-treatment was significantly higher for Group I (Th+ BPA-BNCT) than for Group II (Th- BPA-BNCT): 84 +/- 3% compared to 67 +/- 5%. Pretreatment with thalidomide did not induce statistically significant changes in overall tumor control induced by the beam only, i.e. 15 +/- 5% in Group III (Th+ BO) and 18 +/- 5% in Group IV (Th- BO), or in overall tumor control induced by the high-dose beam only, i.e. 60 +/- 7% in Group V (Th+ hdBO) and 47 +/- 10% in Group VI (Th- hdBO). BPA-BNCT alone (Group II) induced mucositis in precancerous tissue that reached Grades 3-4 in 80% of the animals, whereas pretreatment with thalidomide (Group I) prevented mucositis Grades 3 and 4 completely. Beam-only Group III (Th+ BO) exhibited only Grade 1 mucositis in precancerous tissue, whereas 17% of the animals in beam-only Group IV (Th- BO) reached Grade 2 mucositis. High-dose beam-only group V (Th+ hdBO) exhibited only Grade 2 mucositis, whereas high-dose beam-only group VI (Th- hdBO) reached Grade 3 mucositis in 83% of the animals. In all cases mucositis in precancerous tissue was reversible. No normal tissue radiotoxicity was observed with any of the protocols. Pretreatment with thalidomide enhanced the therapeutic efficacy of BNCT and reduced precancerous tissue toxicity. PMID- 21980959 TI - Factors associated with bone turnover and speed of sound in early and late pubertal females. AB - This cross-sectional study examines whether maturity, body composition, physical activity, dietary intake, and hormonal concentrations are related to markers of bone turnover and tibial speed of sound (tSOS) in premenarcheal (n = 20, 10.1 +/- 1.1 years) and postmenarcheal girls (n = 28, aged 15.0 +/- 1.4 years). Somatic maturity was evaluated using years from age of peak height velocity (aPHV). Daily dietary intake was assessed with a 24-h recall interview, and moderate to very vigorous physical activity (MVPA) was measured using accelerometry. Plasma levels of 25-OH vitamin D, serum levels of insulin-like growth-factor 1 (IGF-1) and leptin, and serum levels of bone turnover markers including osteocalcin (OC), bone-specific alkaline phosphatase (BAP) and cross-linked N-teleopeptide of type I collagen (NTX) were measured using ELISA. OC, BAP, and NTX were significantly higher while IGF-1 and tSOS were lower in the premenarcheal group. The premenarcheal girls were more active and had higher daily energy intake relative to their body mass but there were no group differences in body mass index percentile. Maturity predicted 40%-57% of the variance in bone turnover markers. Additionally, daily energy intake was a significant predictor of OC, especially in the postmenarcheal group. IGF-1 and MVPA were significant predictors of BAP in the group as a whole. However, examined separately, IGF-1 was a predictor of BAP in the premenarcheal group while MVPA was a predictor in the postmenarcheal group. Adiposity and leptin were both negative predictors of tSOS, with leptin being specifically predictive in the postmenarcheal group. In conclusion, while maturity was the strongest predictor of bone markers and tSOS, dietary intake, physical activity, body composition, and hormonal factors further contribute to the variance in bone turnover and bone SOS in young Caucasian females. Further, the predicting factors of bone turnover and tSOS were different within each maturity group. PMID- 21980960 TI - Lipoic acid and moderate swimming improves the estrous cycle and oxidative stress in Wistar rats. AB - The generation of reactive oxygen species resulting from physical activity may trigger adaptive processes at the reproductive level and in the antioxidant defense system itself. The objective of this study was to investigate the effects of moderate daily swimming and lipoic acid (LA) supplementation on estrous cycle duration and pro-oxident and antioxidant markers in young Wistar rats. Animals were submitted to daily swimming (for 1 h) for 30 days, between 1300 h and 1400 h. The following study groups were formed: group 1, sedentary; group 2, submitted to swimming; group 3, sedentary supplemented with 100 mg.kg(-1).day(-1) of LA; and group 4, submitted to swimming and supplementation with 100 mg.kg(-1).day(-1) of LA. The estrous cycle of the animals was evaluated daily, and the following oxidative stress markers were measured: plasma thiobarbituric acid reactive substances (TBARS) and glutathione (GSH), erythrocyte superoxide dismutase (SOD), GSH peroxidase (GPx) and catalase (CAT) activity. The exercise protocol increased estrous cycle duration in group 2, especially in the diestrous phase. There was also a decrease in lipoperoxidation, with enhanced antioxidant activity of SOD and GPx. Group 4 showed no alteration in estrous cycle duration and maintained the beneficial effects on the antioxidant system observed in group 2. The increase in estrous cycle duration and improved oxidative stress markers may be an adaptive response to moderate exercise. LA impeded any exercise-induced alteration in the cycle but preserved improvements in the antioxidant system. PMID- 21980961 TI - Nebivolol for the treatment of heart failure. AB - INTRODUCTION: Heart failure (HF) is a common and disabling disease with a high prevalence in the elderly. Beta-blockers are among the mainstay therapies of HF because they antagonize the deleterious effects of the chronic activation of sympathetic nervous system. In large randomized clinical trials, bisoprolol, carvedilol and metoprolol reduced mortality and cardiovascular hospital admission and, hence, are included in current guidelines for HF treatment. AREAS COVERED: Nebivolol is a third-generation beta-blocker with high selectivity for beta1 adrenoceptors selectivity and vasodilating effects. It also shows antioxidant, antiproliferative and antithrombotic properties. Nebivolol is generally well tolerated. Typical beta-blocker-related adverse events are same as that with placebo, except for bradycardia. In addition, it shows no negative effects on chronic obstructive pulmonary disease, erectile function, and glucose and lipid metabolism. The benefits of nebivolol for HF treatment have been evaluated in the SENIORS trial, where it reduced the composite endpoint of mortality and cardiovascular hospital admission. EXPERT OPINION: Nebivolol is a beta-blocker with distinctive characteristics. Initiated at 1.25 mg and titrated up to 10 mg/day, it has shown safety and efficacy in one large outcome trial, when added to standard medical therapy, in elderly patients (>= 70 years) affected by HF. PMID- 21980962 TI - Theoretical prediction of drug-receptor interactions. AB - The crucial event in the pharmacological action of drugs is the interaction between a drug molecule and its receptor. Molecular recognition and binding affinity of a drug is driven by a flexible steric fit and a molecular field match between two complementary molecular surfaces of the receptor and the approaching ligand. Rational drug design methods, which attempt to predict the free energy change resulting from ligand binding, rely on a detailed knowledge of the physical forces that govern the drug-receptor interactions in several populated configurations of the intermolecular complex. The overall strength of the interaction is determined by the fine balance between the forces contributed by the individual chemical function groups of the two entities and the physiological medium. This paper recounts some basic information about the description of molecular structures and highlights the methods and approximations commonly used to calculate the binding affinity of a drug to its receptor. PMID- 21980963 TI - Gene dose effect of NAT2 variants on the pharmacokinetics of isoniazid and acetylisoniazid in healthy Chinese subjects. AB - BACKGROUND: The aim of this study was to elucidate the gene dose effect of NAT2 and the effect on the pharmacokinetics of isoniazid (INH) and its metabolites acetylisoniazid (AcINH) in Chinese subjects. METHODS: A total of 24 healthy Chinese subjects, consisting of eight homozygous wild types (wt/wt), eight heterozygous mutants (m/wt) and eight homozygous mutants (m/m) for NAT2, were enrolled in the study. The blood samples (0-14 h) of the subjects were taken after oral administration of a single dose (300 mg) of INH. Concentrations of INH and AcINH in plasma were measured by a reversed-phase HPLC method. RESULTS: The ratio of AcINH and INH (R(A/I)) 3 h post-dose of wt/wt, m/wt and m/m groups were 3.22 +/- 1.34, 1.35 +/- 0.20 and 0.22 +/- 0.06, respectively (p<0.01). The area under concentration-time curve (AUC) values of three groups were 10.35 +/- 2.12, 16.34 +/- 3.05, 42.24 +/- 8.51 mg/h/L for INH and 42.19 +/- 8.80, 38.05 +/- 5.32, 19.78 +/- 3.72 mg/h/L for AcINH, respectively (p<0.01). There was a good linear relationship between pharmacokinetic parameters and the number of active NAT2 genes. CONCLUSIONS: The results suggest that there is a conspicuous gene dose effect in the pharmacokinetics of INH and AcINH. This finding may be valuable in the personalized therapy of tuberculosis with INH. PMID- 21980964 TI - Potential pharmacodynamic drug-drug interaction between concomitantly administered lisinopril and diclofenac sodium: a call for appropriate management in hypertensive osteoarthritic patients. AB - BACKGROUND: The present study was designed as an open label, multiple-dose, randomized, parallel trial to evaluate the pharmacodynamic drug-drug interaction of lisinopril and concomitantly administered diclofenac sodium in non-diabetic and diabetic, mild to moderate hypertensive, osteoarthritic patients. METHODS: Post-screening and on inclusion, patients were put on a 2-week washout period and then randomly assigned to either only lisinopril 10 mg or combination of lisinopril 10 mg and diclofenac sodium 100 mg treatments for 8-12 weeks in diseased states of hypertension and osteoarthritis with or without type 2 diabetes mellitus. RESULTS: The blood pressure (BP) control with lisinopril was reduced by concomitantly administered diclofenac sodium in non-diabetic (SBP: p=0.00002; DBP: p=0.000008) and diabetic (SBP: p=0.002; DBP: p=0.001) patients when compared with the patients receiving lisinopril alone. Insulin sensitivity was improved (p=0.00002) and urinary albumin excretion rate was better controlled (p=0.0096) in lisinopril-treated patients when compared with the combination treatment in diabetic pool. Serum creatinine levels increased significantly in non-diabetic patients (p=0.00004) receiving combination treatment. In addition, creatinine clearance (CLCR) and blood urea nitrogen (BUN) were significantly higher in diabetic (CLCR: p<0.00001; BUN: p=0.0098) as well as in non-diabetic (CLCR: p<0.00001; BUN: p=0.03) patients treated with combination treatment. The alterations in serum electrolytes, reduction in % platelet aggregation activity and improvement in lipid profile was more profound with combination treatment in comparison to lisinopril alone. CONCLUSIONS: The antihypertensive efficacy and insulin sensitivity improving property of lisinopril along with the renal function might get worse in hypertensive osteoarthritic patients receiving concomitant treatment of oral diclofenac sodium with lisinopril. In addition to this, close monitoring of serum electrolytes is also suggested to rule out any long-term detrimental effect. PMID- 21980965 TI - Successful tacrolimus treatment following renal transplant in a HIV-infected patient with raltegravir previously treated with a protease inhibitor based regimen. AB - A HIV positive patient who received a cadaveric renal transplantation developed tacrolimus toxicity as manifest by renal failure and decreased consciousness. This was due to atazanavir and ritonavir therapy for her HIV inhibiting the CYP3A4 hepatic enzyme resulting in accumulation of tacrolimus. Her HIV treatment was switched to raltegravir which is metabolized by UGT1A1 which does not affect tacrolimus. Tacrolimus was then reintroduced, and follow-up at 1 year demonstrated successful immunosuppression and undetectable HIV viral loads. PMID- 21980966 TI - Mobility and mobility-related participation outcomes of powered wheelchair and scooter interventions after 4-months and 1-year use. AB - PURPOSE: The aim was to investigate outcomes of powered wheelchair and scooter interventions after 4-months and 1-year use regarding need for assistance when moving around, frequency of mobility-related participation, easiness/difficulty in mobility during participation, and number of participation aspects performed in everyday life. METHOD: The study was a prospective cohort study, using an instrument focusing on mobility-related participation outcomes of mobility device interventions (NOMO 1.0), at baseline, after 4-months and 1-year use. RESULTS: The results show that the outcomes in terms of participation frequency and easiness in mobility occur in a short time perspective, and that the effects remained stable at 1-year follow-up. The frequency of going for a walk increased most prominently (26%). Even though the majority of the participation aspects were not performed, more often they became easier to perform: 56-91% found that shopping, walking and visiting family/friends were easier. Moreover, independence outdoors and indoors increased. CONCLUSIONS: This small study provides knowledge about the outcomes of powered wheelchairs and scooters in terms of mobility and mobility-related participation in real-life situations. The study supports results from former studies, but even so, larger studies are required in order to provide evidence for the effectiveness of powered wheelchairs and scooters. [Box: see text]. PMID- 21980975 TI - Discovery of surfactants for metal/semiconductor separation of single-wall carbon nanotubes via high-throughput screening. AB - We report novel surfactants that can be used for the separation of metallic (M) and semiconducting (S) single-wall carbon nanotubes (SWCNTs). Among the M/S separation methods using surfactants in an aqueous solution, sodium dodecyl sulfate plays a key role in density gradient ultracentrifugation (DGU) and agarose gel separations. In this study, we screened 100 surfactants for M/S separation using a high-throughput screening system. We identified five surfactants, which could be used for both DGU and agarose gel separations, suggesting that the basic principle of these separations is common. These surfactants have relatively low dispersibilities, which is likely due to their common structural features, i.e., straight alkyl tails and charged head groups, and appeared to enable M- and S-SWCNTs to be distinguished and separated. These surfactants should stimulate research in this field and extend the application of electrically homogeneous SWCNTs not only for electronics but also for biology and medicine. PMID- 21980977 TI - Determination of advanced glycation endproducts by LC-MS/MS in raw and roasted almonds (Prunus dulcis). AB - A sensitive and reliable LC-(ESI)MS/MS method was developed and validated for the simultaneous analysis of five common advanced glycation endproducts (AGEs) after enzymatic digestion in raw and roasted almonds. AGEs included carboxymethyl lysine (CML), carboxyethyl-lysine (CEL), pyralline (Pyr), argpyrimidine (Arg-p), and pentosidine (Pento-s). This method allows accurate quantitation of free and AGE-protein adducts of target AGEs. Results indicate that CML and CEL are found in both raw and roasted almonds. Pyr was identified for the first time in roasted almonds and accounted for 64.4% of free plus bound measured AGEs. Arg-p and Pento s were below the limit of detection in all almond samples tested. Free AGEs accounted for 1.3-26.8% of free plus bound measured AGEs, indicating that protein bound forms predominate. The roasting process significantly increased CML, CEL, and Pyr formation, but no significant correlation was observed between these AGEs and roasting temperature. PMID- 21980976 TI - Arginine residues are more effective than lysine residues in eliciting the cellular uptake of onconase. AB - Onconase is an amphibian member of the pancreatic ribonuclease family of enzymes that is in clinical trials for the treatment of cancer. Onconase, which has an abundance of lysine residues, is internalized by cancer cells through endocytosis in a mechanism similar to that of cell-penetrating peptides. Here, we compare the effect of lysine versus arginine residues on the biochemical attributes necessary for Onconase to elicit its cytotoxic activity. In the variant R-Onconase, 10 of the 12 lysine residues in Onconase are replaced with arginine, leaving only the two active-site lysines intact. Cytometric assays quantifying internalization showed a 3-fold increase in the internalization of R-Onconase compared with Onconase. R-Onconase also showed greater affinity for heparin and a 2-fold increase in ribonucleolytic activity. Nonetheless, arginine substitution endowed only a slight increase in toxicity toward human cancer cells. Analysis of denaturation induced with guanidine-HCl showed that R-Onconase has less conformational stability than does the wild-type enzyme; moreover, R-Onconase is more susceptible to proteolytic degradation. These data indicate that arginine residues are more effective than lysine in eliciting cellular internalization but can compromise other aspects of protein structure and function. PMID- 21980978 TI - Impact of ligand exchange in hydrogen production from cobaloxime-containing photocatalytic systems. AB - Ligand exchange on the Co(dmgH)(2)(py)Cl water reduction catalyst was explored under photocatalytic conditions. The photosensitizer fluorescein was connected to the catalyst through the axially coordinated pyridine. While this two-component complex produces H(2) from water under visible light irradiation in the presence of triethanolamine (TEOA), it is less active than a system containing separate fluorescein and [Co(III)(dmgH)(2)(py)Cl] components. NMR and photolysis experiments show that the Co catalyst undergoes pyridine exchange. Interestingly, glyoximate ligand exchange was also observed photocatalytically and by NMR spectroscopy, thereby showing that integrated systems in which the photosensitizer is linked directly to the Co(dmgH)(2)(py)Cl catalyst may not remain intact during H(2) photogeneration. These studies have also given rise to insights into the catalyst decomposition mechanism. PMID- 21980979 TI - Flexible holey graphene paper electrodes with enhanced rate capability for energy storage applications. AB - The unique combination of high surface area, high electrical conductivity and robust mechanical integrity has attracted great interest in the use of graphene sheets for future electronics applications. Their potential applications for high power energy storage devices, however, are restricted by the accessible volume, which may be only a fraction of the physical volume, a consequence of the compact geometry of the stack and the ion mobility. Here we demonstrated that remarkably enhanced power delivery can be realized in graphene papers for the use in Li-ion batteries by controlled generation of in-plane porosity via a mechanical cavitation-chemical oxidation approach. These flexible, holey graphene papers, created via facile microscopic engineering, possess abundant ion binding sites, enhanced ion diffusion kinetics, and excellent high-rate lithium-ion storage capabilities, and are suitable for high-performance energy storage devices. PMID- 21980981 TI - Resistance against tumour necrosis factor alpha apoptosis by the cellular prion protein is cell-specific for oral, colon and kidney cancer cell lines. AB - Since the discovery of PrPC (cellular prion protein), most studies have focused on its role in neurodegenerative diseases, whereas its function outside the nervous system remains obscure. We investigated the ability of PrPC in resisting TNFalpha (tumour necrosis factor alpha) apoptosis in three PrPC-transiently transfected cancer cell lines, renal adenocarcinoma ACHN, oral squamous cell carcinoma HSC-2 and colon adenocarcinoma LS174T. PrPC-expressing ACHN and LS174T cells had higher viabilities compared with the mock-transfected cells, while the transient overexpression of PrPC had minimal overall effect on HSC-2 cells due to its high endogenous PrPC expression. Cell cycles were also analysed, with both PrPC expressing ACHN and LS174T cells having a significantly higher proliferative index than mock-transfected cells. Flow cytometry analysis indicated a G1/S-phase cell cycle transition in both PrPC-expressing ACHN and LS174T cells. PrPC resists TNFalpha apoptosis due to a modest, but statistically significant, cell-specific cytoprotection compared with mock-transfected cells. PMID- 21980982 TI - Evidence-based (S3) guideline for the treatment of androgenetic alopecia in women and in men. AB - Androgenetic alopecia is the most common hair loss disorder, affecting both men and women. Initial signs of androgenetic alopecia usually develop during teenage years leading to progressive hair loss with a pattern distribution. Moreover, its frequency increases with age and affects up to 80 % Caucasian men and 42 % of women. Patients diagnosed with androgenetic alopecia may undergo significant impairment of quality of life. Despite the high prevalence and the variety of therapeutic options available, there have been no national or international evidence-based guidelines for the treatment of androgenetic alopecia in men and women so far. Therefore, the European Dermatology Forum (EDF) initiated a project to develop an evidence-based S3 guideline for the treatment of andro-genetic alopecia. Based on a systematic literature research the efficacy of the currently available therapeutic options was assessed and therapeutic recommendations were passed in a consensus conference. The purpose of the guideline is to provide dermatologists as well as general practitioners with an evidence-based tool for choosing an efficacious and safe therapy for patients with androgenetic alopecia. PMID- 21980983 TI - An analysis of prosthodontic research productivity: geographic, economic, and collaborative perspective. AB - PURPOSE: This study evaluated the quantity of prosthodontic literature produced globally by continent in three prosthodontic journals over a 10-year period, 1998 2008. Prosthodontic research productivity relative to economic status of countries and collaboration among countries grouped by economic status was assessed. MATERIALS AND METHODS: Three peer-reviewed prosthodontic journals were used for the analysis of articles published in 1998, 2003, and 2008: The Journal of Prosthetic Dentistry, International Journal of Prosthodontics, and Journal of Prosthodontics. The country of every author listed for each included article was recorded. The number of articles published by each continent and each country was reported. Countries were grouped according to the World Bank economic classification system, and the number of articles published by each economic class was found. RESULTS: The majority of publications over the 10-year period were produced in Asia (Japan), Europe (Germany), and North America (USA). Productivity declined by 14.4% in high-income countries while it increased in upper middle-, lower middle-, and low-income countries. The majority of publications written by upper and lower middle- and low-income countries were independent works. Articles resulting from collaboration increased over time for all economic classes of countries. CONCLUSIONS: The origins of prosthodontic literature are becoming more geographically and economically diverse, with increased contributions from Africa, Asia, and South America, and middle- and low income countries between 1998 and 2008. Collaboration between high-income countries and the other economic group countries increased over time. PMID- 21980984 TI - The Fish Barcode of Life (FISH-BOL) special issue. PMID- 21980985 TI - DNA barcoding of billfishes. AB - DNA barcoding is a method promising fast and accurate identification of animal species based on the sequencing of the mitochondrial c oxidase subunit (COI) gene. In this study, we explore the prospects for DNA barcoding in one particular fish group, the billfishes (suborder Xiphioidei--swordfish, marlins, spearfishes, and sailfish). We sequenced the mitochondrial COI gene from 296 individuals from the 10 currently recognized species of billfishes, and combined these data with a further 57 sequences from previously published projects. We also sequenced the rhodopsin gene from a subset of 72 individuals to allow comparison of mitochondrial results against a nuclear marker. Five of the 10 species are readily distinguishable by COI barcodes. Of the rest, the striped marlin (Kajikia audax) and white marlin (K. albida) show highly similar sequences and are not unambiguously distinguishable by barcodes alone, likewise are the three spearfishes Tetrapturus angustirostris, T. belone, and T. pfluegeri. We discuss the taxonomic status of these species groups in light of our and other data, molecular and morphological. PMID- 21980986 TI - FISH-BOL and seafood identification: geographically dispersed case studies reveal systemic market substitution across Canada. AB - BACKGROUND AND AIMS: The Fish Barcode of Life campaign involves a broad international collaboration among scientists working to advance the identification of fishes using DNA barcodes. With over 25% of the world's known ichthyofauna currently profiled, forensic identification of seafood products is now feasible and is becoming routine. MATERIALS AND METHODS: Driven by growing consumer interest in the food supply, investigative reporters from five different media establishments procured seafood samples (n = 254) from numerous retail establishments located among five Canadian metropolitan areas between 2008 and 2010. The specimens were sent to the Canadian Centre for DNA Barcoding for analysis. By integrating the results from these individual case studies in a summary analysis, we provide a broad perspective on seafood substitution across Canada. RESULTS: Barcodes were recovered from 93% of the samples (n = 236), and identified using the Barcode of Life Data Systems "species identification" engine ( www.barcodinglife.org ). A 99% sequence similarity threshold was employed as a conservative matching criterion for specimen identification to the species level. Comparing these results against the Canadian Food Inspection Agency's "Fish List" a guideline to interpreting "false, misleading or deceptive" names (as per s 27 of the Fish Inspection regulations) demonstrated that 41% of the samples were mislabeled. Most samples were readily identified; however, this was not true in all cases because some samples had no close match. Others were ambiguous due to limited barcode resolution (or imperfect taxonomy) observed within a few closely related species complexes. The latter cases did not significantly impact the results because even the partial resolution achieved was sufficient to demonstrate mislabeling. CONCLUSION: This work highlights the functional utility of barcoding for the identification of diverse market samples. It also demonstrates how barcoding serves as a bridge linking scientific nomenclature with approved market names, potentially empowering regulatory bodies to enforce labeling standards. By synchronizing taxonomic effort with sequencing effort and database curation, barcoding provides a molecular identification resource of service to applied forensics. PMID- 21980987 TI - Predicting overall viability of cord blood harvests. AB - BACKGROUND: Cord blood (CB) is a product rich in primitive adult stem cells used in hematopoietic stem cell transplantation. After collection, the CB is transported to a facility where the unit is processed and then frozen up to 48 hours later. These processes can lead to compromised white blood cell (WBC) viability. This study investigates the factors that affect WBC viability before freezing of the cells. STUDY DESIGN AND METHODS: We retrospectively analyzed WBC viability from 9918 CB collections harvested from 2003 to 2010 to determine if collection volume and time to freezing (TTF) had a significant effect on WBC viability. CB was collected in dispersed clinical locations by local staff trained to the same methods. CB was transported to the central lab under controlled conditions for analysis and processing. RESULTS: The collected CB units had a mean volume of 77.1 +/- 31.3 mL, mean WBC count of 10.5 * 10(8) +/- 5.6 * 10(8) , mean total CD34+ cell count of 4.0 * 10(6) +/- 3.7 * 10(6) , and mean WBC viability of 91.7% +/- 6.5%. WBC viability was most significantly affected by the volume of CB collected and the TTF. As collection volumes increased, WBC viability increased, with mean viability of 95.0% +/- 3.5% in CB collections of more than 120 mL. Decreased viability was associated with volumes of less than 60 mL and TTF of more than 24 hours. From these data we have developed decision tables that estimate WBC viability based on CB volume and TTF. CONCLUSION: This study identifies optimal TTF for different collection volumes to maintain WBC viability of the collected CB. PMID- 21980988 TI - Polyphyly of non-bioluminescent Vibrio fischeri sharing a lux-locus deletion. AB - This study reports the first description and molecular characterization of naturally occurring, non-bioluminescent strains of Vibrio fischeri. These 'dark' V. fischeri strains remained non-bioluminescent even after treatment with both autoinducer and aldehyde, substrate additions that typically maximize light production in dim strains of luminous bacteria. Surprisingly, the entire lux locus (eight genes) was absent in over 97% of these dark V. fischeri strains. Although these strains were all collected from a Massachusetts (USA) estuary in 2007, phylogenetic reconstructions allowed us to reject the hypothesis that these newly described non-bioluminescent strains exhibit monophyly within the V. fischeri clade. These dark strains exhibited a competitive disadvantage against native bioluminescent strains when colonizing the light organ of the model V. fischeri host, the Hawaiian bobtail squid Euprymna scolopes. Significantly, we believe that the data collected in this study may suggest the first observation of a functional, parallel locus-deletion event among independent lineages of a non-pathogenic bacterial species. PMID- 21980989 TI - Risk analysis for deterioration of renal function after pancreas alone transplant. AB - The risk of progression to renal replacement after pancreas transplant alone (PTA) is a concern in patients with pre-transplant estimated glomerular filtration rate (eGFR) < 70 mL/min/1.73 m(2). This is a retrospective, single center risk analysis of potential factors affecting renal function after PTA. Twenty-four patients, transplanted over a three-yr period, with functioning pancreatic grafts at the study's end point were included. High tacrolimus levels (> 12 mg/dL) at six months post-transplant was the only independent risk factor identifying a substantial decline in native renal function by Cox regression analysis (HR = 14.300, CI = 1.271-160.907, p = 0.031). The presence of severe pre transplant proteinuria (urine Pr/Cr >= 100 mg/mmol) marginally failed to reach significance (p = 0.056). Low eGFR levels alone (<= 45 and <= 40 mL/min/1.73 m(2)) at the time of transplant did not correlate with substantial decline in renal function. Our data suggest that PTA is a justifiable therapy for patients with hypoglycemia unawareness or other life-threatening diabetic complications, even in those with borderline renal function, provided that they do not suffer from severe proteinuria and appropriate monitoring and tailoring of immunosuppression is ensured. PMID- 21980990 TI - Juvenile xanthogranuloma with lichenoid appearance. AB - Juvenile xanthogranulomas are benign histiocytic cell tumors that develop mainly in infancy and early childhood and then spontaneously regress. We report a 2-year old boy who presented with generalized eruption of a mixture of micronodular and macronodular juvenile xanthogranuloma with a large number of widely distributed lichenoid papules. Light microscopic and immunocytochemical analyses of the lesion were consistent with juvenile xanthogranuloma. Abdominal ultrasonography did not detect any visceral lesions, and brain magnetic resonance imaging did not detect any mass lesions. We decided to observe the course without treatment in this case because there are no internal masses of juvenile xanthogranuloma. Regular follow up has therefore been scheduled. To our knowledge, this is the third report of a case demonstrating juvenile xanthogranuloma with lichenoid appearance. Future analyses of various cytokines such as granulocyte-macrophage colony-stimulating factor and/or tumor necrosis factor-alpha in juvenile xanthogranuloma lesions should be of great help in elucidating the pathogenesis of this disease. PMID- 21980991 TI - Pacing as a treatment modality in migraine and tension-type headache. AB - PURPOSE: To review the pacing literature; describe the use of pacing in a specialty headache clinic; and provide client feedback regarding the effectiveness of pacing in headache self-management. METHOD: The evidence for this report was derived from a structured literature review, an established pacing intervention program for patients with headache, and patient self-report questionnaire. RESULTS: There are frequent references to pacing in the chronic pain and rheumatic disease literature, but no universal definition and, until recently, few outcome studies. References to pacing in the headache literature are limited. For a small sub-group of clients at a specialty headache clinic (n = 20), pacing principles taught by occupational therapists were reported to prevent increases in headache intensity (70%); decrease headache intensity (65%), and shorten the duration of a headache (40%). Additionally, 70% of respondents used pacing to prevent headache onset. Pacing was seen to contribute to increased quality of life, headache self-efficacy, function, and independence. There were a variety of opinions regarding the most helpful pacing components. The most frequently endorsed were identify and prioritize responsibilities; balance activity and rest; schedule regular rest breaks; and delegate or eliminate tasks. CONCLUSIONS: Pacing appears to play an important role in headache self management. More pacing research is required in both headache and chronic pain populations. PMID- 21980992 TI - Effects of high-dose large neutral amino acid supplementation on exercise, motor skill, and mental performance in Australian Rules Football players. AB - This study investigated the effects of high-dose large neutral amino acid (LNAA) supplementation on attenuating fatigue-induced decrements in exercise and motor skill performance in Australian Rules Football (ARF) players. Fifteen subelite ARF players participated in 3 testing sessions separated by 7 days. Players completed an initial control trial involving a reactive motor skills test (RMST) and a reactive agility test (RAT) carried out before and after fatiguing exercise. In the subsequent experimental trials, players ingested a serotonin depleting or protein control (PC) LNAA mixture 3 h before testing, allocated in a double-blind randomized cross-over design. Blood samples were taken at presupplementation and pre- and postexercise for analysis of plasma amino acid, insulin, and metabolite concentrations. The effect of the LNAA was established as the difference in the change in the mean RMST and RAT test scores among the depleting, PC, and baseline (BL) trials. Mean overall repetition time of the RAT was moderately improved by -5.2% +/- 3.4% (mean +/- 90% confidence limits; effect size -0.45 +/- 0.28) after ingestion of the serotonin-depleting mixture compared with the BL trial. Serotonin-depleting and PC supplements had a divergent effect on mean repetition time after fatiguing exercise in RMST: depleting serotonin elicited a small improvement (-3.0% +/- 2.7%) in motor skill performance in contrast to a small decrement (2.4% +/- 2.7%) after ingestion of the PC mixture, when compared to the BL. High-dose serotonin-"depleting" LNAA supplementation given 3 h prior to intermittent high-intensity exercise improved reactive motor skill and agility performance in ARF players. PMID- 21980993 TI - Exercise-induced dehydration with and without environmental heat stress results in increased oxidative stress. AB - While in vitro work has revealed that dehydration and hyperthermia can elicit increased cellular and oxidative stress, in vivo research linking dehydration, hyperthermia, and oxidative stress is limited. The purpose of this study was to investigate the effects of exercise-induced dehydration with and without hyperthermia on oxidative stress. Seven healthy male, trained cyclists (power output (W) at lactate threshold (LT): 199 +/- 19 W) completed 90 min of cycling exercise at 95% LT followed by a 5-km time trial (TT) in 4 trials: (i) euhydration in a warm environment (EU-W, control), (ii) dehydration in a warm environment (DE-W), (iii) euhydration in a thermoneutral environment (EU-T), and (iv) dehydration in a thermoneutral environment (DE-T) (W: 33.9 +/- 0.9 degrees C; T: 23.0 +/- 1.0 degrees C). Oxidized glutathione (GSSG) increased significantly postexercise in dehydration trials only (DE-W: p < 0.01, DE-T: p = 0.03), and while not significant, total glutathione (TGSH) and thiobarbituric acid reactive substances (TBARS) tended to increase postexercise in dehydration trials (p = 0.08 for both). Monocyte heat shock protein 72 (HSP72) concentration was increased (p = 0.01) while lymphocyte HSP32 concentration was decreased for all trials (p = 0.02). Exercise-induced dehydration led to an increase in GSSG concentration while maintenance of euhydration attenuated these increases regardless of environmental condition. Additionally, we found evidence of increased cellular stress (measured via HSP) during all trials independent of hydration status and environment. Finally, both 90-min and 5-km TT performances were reduced during only the DE-W trial, likely a result of combined cellular stress, hyperthermia, and dehydration. These findings highlight the importance of fluid consumption during exercise to attenuate thermal and oxidative stress during prolonged exercise in the heat. PMID- 21980994 TI - Reproducibility of velocity-dependent power: before and after lengthening contractions. AB - The determination of power using isokinetic testing has been shown to be highly reliable. However, isotonic and isokinetic testing involve specific mechanical constraints that likely necessitate different neuromuscular strategies. Therefore, the purpose here was to establish test-retest intrarater reliability (separated by 7 days) of loaded maximal shortening velocity and velocity dependent power of the ankle dorsiflexors using the isotonic mode of the Biodex dynamometer (i) at baseline and (ii) throughout recovery following 150 high intensity lengthening contractions. Intraclass correlation coefficients (ICC)(2,1) with 95% CIs were used to determine relative reliability, whereas absolute reliability included typical error (TEM) and typical error expressed as a coefficient of variation (TEM(CV)). Twenty-four young men and women volunteered for the study. Maximal shortening velocity and power were determined with a fixed resistance set at 20% of maximal voluntary isometric contraction across 2 testing sessions separated by 7 days. ICCs were 0.93 and 0.98 for maximal shortening velocity and peak power, respectively. Following the lengthening contractions, ICCs indicated high reliability for maximal shortening velocity and peak power, 0.86 and 0.94, respectively, suggesting that a similar amount of fatigue was incurred on both days. Measures of absolute reliability for maximal shortening velocity and peak power also yielded high reliability. The isotonic mode is highly reliable when testing velocity-dependent power of the ankle dorsiflexors at baseline and following fatiguing lengthening contractions. The high reliability of this measure is encouraging and suggests that the isotonic mode can be used in various settings to track group changes before and after training and following fatigue and lengthening contractions. PMID- 21980995 TI - Self-assembly of poly(ionic liquid)s: polymerization, mesostructure formation, and directional alignment in one step. AB - This paper reports on the highly ordered and tunable inner structure of poly(ionic liquid) nanoparticles, which formed spontaneously by precipitation polymerization from water. Without added stabilizer, these "latexes" are much smaller (20-40 nm in diameter) than usual polymer latexes and exhibit either multilamellar or unilamellar vesicular morphology, depending on the tail length of the quaternizing alkyl chains. The simplicity in the synthesis and composition and the high complexity of the ordered structures that resemble liposomes expand the classical profile of homopolymer self-assembly. In addition, unidirectional superassembly to a nanoworm mesostructure is found at elevated concentrations, indicating that the ionic liquid liposomes are apt to integrate into further hierarchical assembly schemes. PMID- 21980996 TI - Galega orientalis is more diverse than Galega officinalis in Caucasus--whole genome AFLP analysis and phylogenetics of symbiosis-related genes. AB - Legume plants can obtain combined nitrogen for their growth in an efficient way through symbiosis with specific bacteria. The symbiosis between Rhizobium galegae and its host plant Galega is an interesting case where the plant species G. orientalis and G. officinalis form effective, nitrogen-fixing, symbioses only with the appropriate rhizobial counterpart, R. galegae bv. orientalis and R. galegae bv. officinalis, respectively. The symbiotic properties of nitrogen fixing rhizobia are well studied, but more information is needed on the properties of the host plants. The Caucasus region in Eurasia has been identified as the gene centre (centre of origin) of G. orientalis, although both G. orientalis and G. officinalis can be found in this region. In this study, the diversity of these two Galega species in Caucasus was investigated to test the hypothesis that in this region G. orientalis is more diverse than G. officinalis. The amplified fragment length polymorphism fingerprinting performed here showed that the populations of G. orientalis and R. galegae bv. orientalis are more diverse than those of G. officinalis and R. galegae bv. officinalis, respectively. These results support the centre of origin status of Caucasus for G. orientalis at a genetic level. Analysis of the symbiosis-related plant genes NORK and Nfr5 reveals remarkable diversity within the Nfr5 sequence, although no evidence of adaptive evolution could be found. PMID- 21980997 TI - Cucumber mosaic virus: viral genes as virulence determinants. AB - TAXONOMIC RELATIONSHIPS: Cucumber mosaic virus (CMV) is the type species of the genus Cucumovirus in the family Bromoviridae, which also encompasses the Peanut stunt virus (PSV) and the Tomato aspermy virus (TAV). Nucleotide sequence similarity among these three cucumoviruses is 60%-65%. CMV strains are divided into three subgroups, IA, IB and II, based on the sequence of the 5' untranslated region of the genomic RNA 3. Overall nucleotide sequence similarity among CMV strains is approximately 70%-98%. GEOGRAPHICAL DISTRIBUTION, HOST RANGE AND SYMPTOMATOLOGY: CMV is distributed worldwide, primarily in temperate to tropical climate zones. CMV infects more than 1200 species of 100 plant families, including monocot and dicot plants. Symptoms caused by CMV infection vary with the host species and/or CMV strain, and include mosaic, stunt, chlorosis, dwarfing, leaf malformation and systemic necrosis. CMV disease is spread primarily by aphid transmission in a nonpersistent manner. PHYSICAL PROPERTIES: In tobacco sap, the thermal inactivation point of the viral infectivity is approximately 70 degrees C (10 min), the dilution end-point is approximately 10( 4) and viral infectivity is lost after a few days of exposure to 20 degrees C. Viral infectivity can be retained in freeze-dried tissues and in the form of virions purified using 5 mm sodium borate, 0.5 mm ethylenediaminetetraacetic acid and 50% glycerol (pH 9.0) at -20 degrees C. CMV particles are isometric, approximately 28-30 nm in diameter and are composed of 180 capsid subunits arranged in pentamer-hexamer clusters with T= 3 symmetry. The sedimentation coefficient (s(20) ,(w) ) is c. 98 S and the particle weight is (5.8-6.7) * 10(6) Da. The virions contain 18% RNA. The RNA-protein interactions that stabilize the CMV virions are readily disrupted by sodium dodecylsulphate or neutral chloride salts. GENOMIC PROPERTIES: The genomic RNAs are single-stranded messenger sense RNAs with 5' cap and 3' tRNA-like structures containing at least five open reading frames. The viral RNA consists of three genomic RNAs, RNA 1 (c. 3.3 kb), RNA 2 (c. 3.0 kb) and RNA 3 (c. 2.2 kb), and two subgenomic RNAs, RNA 4 (c. 1.0 kb) and RNA 4A (c. 0.7 kb). The 3' untranslated regions are conserved across all viral RNAs. CMV is often accompanied by satellite, noncoding, small, linear RNA that is nonhomologous to the helper CMV. PMID- 21980998 TI - Tracking national and regional spatial-temporal mortality risk associated with NO2 concentrations in Canada: a Bayesian hierarchical two-level model. AB - The association between daily variations in urban air quality and mortality has been well documented using time series statistical methods. This approach assumes a constant association over time. We develop a space-time dynamic model that relaxes this assumption, thus more directly examining the hypothesis that improvements in air quality translate into improvements in public health. We postulate a Bayesian hierarchical two-level model to estimate annual mortality risks at regional and national levels and to track both risk and heterogeneity of risk within and between regions over time. We illustrate our methods using daily nitrogen dioxide concentrations (NO2) and nonaccidental mortality data collected for 1984-2004 in 24 Canadian cities. Estimates of risk and heterogeneity are compared by cause of mortality (cardio-pulmonary [CP] versus non-CP) and season, respectively. Over the entire period, the NO2 risk for CP mortality was slightly lower but with a narrower credible interval than that for non-CP mortality, mainly due to an unusually low risk for a single year (1998). Warm season NO2 risk was higher than cold season risk for both CP and non-CP mortality. For 21 years overall there were no significant differences detected among the four regional NO2 risks. We found overall that there was no strong evidence for time trends in NO2 risk at national or regional levels. However, an increasing linear time trend in the annual between-region heterogeneities was detected, which suggests the differences in risk among the four regions are getting larger, and further studies are necessary to understand the increasing heterogeneity. PMID- 21980999 TI - DNA base pair hybridization and water-mediated metastable structures studied by molecular dynamics simulations. AB - The base pair hybridization of a DNA segment was studied using molecular dynamics simulation. The results show the obvious correlation between the probability of successful hybridization and the accessible surface area to water of two successive base pairs, including the unpaired base pair adjacent to paired base pair and this adjacent paired base pair. Importantly, two metastable structures in an A-T base pair were discovered by the analysis of the free energy landscape. Both structures involved addition of a water molecule to the linkage between the two nucleobases in one base pair. The existence of the metastable structures provide potential barriers to the Watson-Crick base pair, and numerical simulations show that those potential barriers can be surmounted by thermal fluctuations at higher temperatures. These studies contribute an important step toward the understanding of the mechanism in DNA hybridization, particularly the effect of temperature on DNA hybridization and polymerase chain reaction. These observations are expected to be helpful for facilitating experimental bio/nanotechnology designs involving fast hybridization. PMID- 21981000 TI - Polyphenol fatty acid esters as serine protease inhibitors: a quantum-chemical QSAR analysis. AB - We investigated the ability of polyphenol fatty acid esters to inhibit the activity of serine proteases trypsin, thrombin, elastase and urokinase. Potent protease inhibition in micromolar range was displayed by rutin and rutin derivatives esterified with medium and long chain, mono- and polyunsaturated fatty acids (1e-m), followed by phloridzin and esculin esters with medium and long fatty acid chain length (2a-d, 3a-d), while unmodified compounds showed only little or no effect. QSAR study of the compounds tested provided the most significant parameters for individual inhibition activities, i.e. number of hydrogen bond donors for urokinase, molecular volume for thrombin, and solvation energy for elastase. According to the statistical analysis, the action of elastase inhibitors is opposed to those of urokinase and thrombin. Cluster analysis showed two groups of compounds: original polyphenols together with rutin esters with short fatty acid chain length and rutin esters with long fatty acid chain length. PMID- 21981001 TI - Synthesis and anticonvulsant activity of some 2-(2-{1-[substituted phenyl]ethylidene}hydrazinyl)-4-(4-methoxy-phenyl)-6-oxo-1,6-dihydro-pyrimidine-5 carbonitrile. AB - A series of dihydro-pyrimidine-5-carbonitrile derivatives (3-16) were synthesized and evaluated for their anticonvulsant activity against MES and scPTZ models. Motor impairment screening was carried out by rotarod test method and CNS depressant effect was determined by Porsolt's force swim pool method. Compounds 4 and 9 having p-substituted bromo and m-substituted nitro groups, respectively, were found to be most active showing activity both in MES and scPTZ screen at lower doses of 30 mgkg(-1) at 0.5 h and 100 mgkg(-1) at 4 h. In the rotarod motor impairment screen, compound 4 did not show any motor impairment even at the maximum dose of 300 mgkg(-1); however, compound 9 showed motor impairment at 300 mgkg(-1) dose after 4.0 h. The compounds were also tested for their CNS depression effect. The compounds 4 and 9 showed 41.38 and 43.44% increase in immobility time with respect to control. The pharmacophore hypothesis also fits best for compounds 4 and 9. PMID- 21981002 TI - Synthesis and biological evaluation of novel benzothiazole clubbed fluoroquinolone derivatives. AB - In the present investigation, synthesis and anti-bacterial, analgesic and anthelmintic evaluation of a novel series of fluoroquinolone derivatives clubbed with benzothiazole moeity has been described. The synthesized compounds were characterised by spectral analysis (IR and (1)H NMR). Preliminary results indicated that the most of the synthesized compounds demonstrated good activities against gram negative and gram positive bacterial strains. Compounds 5a, 5b, 5f and 5k demonstrated potent anti-bacterial activities. Compound 5a exhibited most potent anti-bacterial activity with MIC values of 04, 03, 08 and 15 ug/ mL against B. subtilis, S. aureus, E. coli and P. aeruginosa. Analogs 5a, 5c, 5g and 5h showed promising anthelmintic activity against Eisemia foetida in a low concentration as compared to standard drug piperazine citrate with mean paralysis time ranging 22.60 +/- 2.46 to 31.60 +/- 3.07 min. All synthesized compounds depicted good in vivo analgesic activity with compound 5a exhibiting the most potent activity of 55.19% inhibition of writhing in comparison to the standard drug. PMID- 21981003 TI - Heterocyclic compounds as carbonic anhydrase inhibitor. AB - The carbonic anhydrases (CAs, EC 4.2.1.1) constitute interesting targets for the design of pharmacological agents useful in the treatment or prevention of a variety of disorders such as, glaucoma, acid-base disequilibria, epilepsy, and other neuromuscular diseases, altitude sickness, edema, and obesity. A quite new and unexpected application of the CA inhibitors (CAIs) is with regard to their potential use in the management (imaging and treatment) of hypoxic tumors. A series of sulfonamides, including some clinically used derivatives like acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, benzolamide, and sulpiride, or indisulam, a compound in clinical development as antitumor drug, as well as the sulfamate antiepileptic drug topiramate have been reported to inhibit various human carbonic anhydrase isozyme. Various heterocyclic sulfonamides have been reported in this review with their potency to inhibit different carbonic anhydrases isozymes. PMID- 21981004 TI - Evaluation of the use of Syzygium cumini fruit extract as an antioxidant additive in orange juice and its sensorial impact. AB - This work is an exploratory study of the possibility of promoting the consumption of Syzygium cumini fruit by adding its extract to orange juice making good use of its functional (antioxidant) properties. S. cumini fruit extract was characterized in terms of its anthocyanin content (2.11 g/100 g expressed in cyanidine-3-glucoside equivalents), total phenolic compounds (360 mg/100 g expressed in gallic acid equivalents) and antioxidant capacity evaluated by the 2,2-diphenyl-1-picrylhydrazyl free radical scavenging method. The effects of the addition of S. cumini fruit crude extract as well as its chromatographic fractions on the juice were assessed chemically by headspace solid-phase micro extraction and gas chromatography coupled with a mass spectrometry detector. Only six compounds had their chromatographic peak intensities clearly changed and the results are discussed in terms of the inhibition of the formation of 2-octanone, hexanol, alpha-copaene, and alpha-panasinsene and the conservation of octyl acetate and p-menth-1-en-9-ol. Sensory evaluation of orange juice with and without S. cumini crude extract addition did not show any significant differences in the sensorial profile, discriminative and acceptance tests. PMID- 21981005 TI - Flexible diphosphine ligands with overall charges of 0, +1, and +2: critical role of the electrostatics in favoring trans over cis coordination. AB - The influence of the formal electrostatic interaction on the cis/trans coordination mode at a PdCl(2) center is investigated in a family of isostructural flexible diphosphine ligands Ph(2)P-X-C(6)H(4)-Y-PPh(2), where X and Y stand for neutral or cationic N,C-imidazolylene linkers. While the neutral and monocationic diphosphine spontaneously behave as classical cis-chelating ligands, only the dicationic diphosphine, where the electrostatic repulsion between the formal positive charges specifically takes place, is observed to behave as a trans-chelating ligand. The crucial role of electrostatics is analyzed on the basis of (31)P NMR data in solution and X-ray diffraction data in the crystal state. Comparative theoretical studies of the cis- and trans-chelated complexes, including EDA, static (31)P NMR, MESP, and AIM analyses, have been undertaken on the basis of DFT calculations in the gas phase or in the acetonitrile continuum. Whereas the cis-coordination mode is shown to be thermodynamically favored for the neutral ligand, the trans-coordination mode is found to be preferred for the dicationic homologue. The stereochemical preference is thus shown to be parallel to the expected effect of the formal electrostatic interaction. The results open perspectives for control of the cis- and trans chelating behavior of flexible bidentate ligands by more or less reversible charge transfer at the periphery of the coordination sphere of a metallic center. PMID- 21981006 TI - Post-Golgi supramolecular assembly of aquaporin-4 in orthogonal arrays. AB - The supramolecular assembly of aquaporin-4 (AQP4) in orthogonal arrays of particles (OAPs) involves N-terminus interactions of the M23-AQP4 isoform. We found AQP4 OAPs in cell plasma membranes but not in endoplasmic reticulum (ER) or Golgi, as shown by: (i) native gel electrophoresis of brain and AQP4-transfected cells, (ii) photobleaching recovery of green fluorescent protein-AQP4 chimeras in live cells and (iii) freeze-fracture electron microscopy (FFEM). We found that AQP4 OAP formation in plasma membranes, but not in the Golgi, was not related to AQP4 density, pH, membrane lipid composition, C-terminal PDZ domain interactions or alpha-syntrophin expression. Remarkably, however, fusion of AQP4-containing Golgi vesicles with (AQP4-free) plasma membrane vesicles produced OAPs, suggesting the involvement of plasma membrane factor(s) in AQP4 OAP formation. In investigating additional possible determinants of OAP assembly we discovered membrane curvature-dependent OAP assembly, in which OAPs were disrupted by extrusion of plasma membrane vesicles to ~110 nm diameter, but not to ~220 nm diameter. We conclude that AQP4 supramolecular assembly in OAPs is a post-Golgi phenomenon involving plasma membrane-specific factor(s). Post-Golgi and membrane curvature-dependent OAP assembly may be important for vesicle transport of AQP4 in the secretory pathway and AQP4-facilitated astrocyte migration, and suggests a novel therapeutic approach for neuromyelitis optica. PMID- 21981012 TI - Self-standing polyelectrolyte multilayer films based on light-triggered disassembly of a sacrificial layer. AB - In the present article, we present a new and convenient optical method for the preparation of self-standing polyelectrolyte multilayer films. This method employs the disassembly of a sacrificial layer stratum composed of five poly(acrylate, merocyanine) PMC/poly(diallyldimethylammonium chloride) PDADMAC bilayers, which is triggered by the irradiation with visible light. This leads to the conversion of the zwitterionic PMC to its neutral isomer poly(acrylate, spiropyran) PSP, whereby the attractive ionic interactions between the neighboring bilayers vanish. The disassembly of the sacrificial layers in deionized water was completed within 47 s, when in-situ monitored at the maximum absorbance of PSP (lambda = 360 nm), employing UV/visible spectrometry. Surprisingly, the disassembly duration of the sacrificial layers increased very little with an upper target film composed of 75 PDADMAC/PSS bilayers. The quick release of a thick target film (d ~ 232 nm) composed of 100 (PDADMAC)/(PSS) bilayers in a large scale (7 * 18 mm(2)) could be ascribed not only to the vanished electrostatic attractive interaction between the layer pairs but also to increased hydrophobicity of the sacrificial layer element due to the photoisomerization of zwitterionic ionic PMC to neutral PSP. The unique advantages of this method as compared to the conventional approaches are demonstrated with the fast release (~2 min) of self-standing film combined with a well-defined, thin sacrificial layer (d ~ 30 nm). Moreover, harsh release conditions are also avoided, which significantly broadens the choice of materials that can be incorporated into the free-standing film. PMID- 21981007 TI - Establishment of a new cell-based assay to measure the activity of sweeteners in fluorescent food extracts. AB - Taste receptors have been defined at the molecular level in the past decade, and cell-based assays have been developed using cultured cells heterologously expressing these receptors. The most popular approach to detecting the cellular response to a tastant is to measure changes in intracellular Ca(2+) concentration using Ca(2+)-sensitive fluorescent dyes. However, this method cannot be applied to food-derived samples that contain fluorescent substances. To establish an assay system that would be applicable to fluorescent samples, we tested the use of Ca(2+)-sensitive photoproteins, such as aequorin and mitochondrial clytin-II, as Ca(2+) indicators in a human sweet taste receptor assay. Using these systems, we successfully detected receptor activation in response to sweetener, even when fluorescent compounds coexisted. This luminescence-based assay will be a powerful tool to objectively evaluate the sweetness of food-derived samples even at an industry level. PMID- 21981013 TI - Visible light photocatalytic H2-production activity of CuS/ZnS porous nanosheets based on photoinduced interfacial charge transfer. AB - Visible light photocatalytic H(2) production through water splitting is of great importance for its potential application in converting solar energy into chemical energy. In this study, a novel visible-light-driven photocatalyst was designed based on photoinduced interfacial charge transfer (IFCT) through surface modification of ZnS porous nanosheets by CuS. CuS/ZnS porous nanosheet photocatalysts were prepared by a simple hydrothermal and cation exchange reaction between preformed ZnS(en)(0.5) nanosheets and Cu(NO(3))(2). Even without a Pt cocatalyst, the as-prepared CuS/ZnS porous nanosheets reach a high H(2) production rate of 4147 MUmol h(-1) g(-1) at CuS loading content of 2 mol % and an apparent quantum efficiency of 20% at 420 nm. This high visible light photocatalytic H(2)-production activity is due to the IFCT from the valence band of ZnS to CuS, which causes the reduction of partial CuS to Cu(2)S and thus enhances H(2)-production activity. This work not only shows a possibility for substituting low-cost CuS for noble metals in the photocatalytic H(2) production but also for the first time exhibits a facile method for enhancing H(2) production activity by photoinduced IFCT. PMID- 21981014 TI - Perforin is recaptured by natural killer cells following target cells stimulation for cytotoxicity. AB - When encountering target cells, NK (natural killer) cells exocytose Pfn (perforin) and granzyme B to kill challengers. We previously reported that granzyme B is recycled and reused by NK cells via clathrin-dependent endocytosis. However, whether Pfn, a main secretory vesicle content, indispensible to granzyme B killing, undergoes endocytosis remains unknown. We demonstrate that Pfn is recaptured by early endosomes of NK cells via a clathrin-dependent endocytosis after target cell stimulation. Inhibition of clathrin-dependent endocytosis significantly attenuated the cytotoxicity of NK cells. The data suggest that the recovery of Pfn contributes to the cytotoxicity of NK cells. The assay of endocytosis of lytic molecule presents a particular focus for exploring the mechanism of abnormal cytotoxicity of NK cells. PMID- 21981015 TI - Defective etioplasts observed in variegation mutants may reveal the light independent regulation of white/yellow sectors of Arabidopsis leaves. AB - Leaf variegation resulting from nuclear gene mutations has been used as a model system to elucidate the molecular mechanisms of chloroplast development. Since most variegation genes also function in photosynthesis, it remains unknown whether their roles in photosynthesis and chloroplast development are distinct. Here, using the variegation mutant thylakoid formation1 (thf1) we show that variegation formation is light independent. It was found that slow and uneven chloroplast development in thf1 can be attributed to defects in etioplast development in darkness. Ultrastructural analysis showed the coexistence of plastids with or without prolamellar bodies (PLB) in cells of thf1, but not of WT. Although THF1 mutation leads to significant decreases in the levels of Pchlide and Pchllide oxidoreductase (POR) expression, genetic and 5 aminolevulinic acid (ALA)-feeding analysis did not reveal Pchlide or POR to be critical factors for etioplast formation in thf1. Northern blot analysis showed that plastid gene expression is dramatically reduced in thf1 compared with that in WT, particularly in the dark. Our results also indicate that chlorophyll biosynthesis and expression of plastidic genes are coordinately suppressed in thf1. Based on these results, we propose a model to explain leaf variegation formation from the plastid development perspective. PMID- 21981016 TI - Metabolic modulation of cytokine-induced brain endothelial adhesion molecule expression. AB - OBJECTIVE: Cytokines contribute to cerebro-vascular inflammatory and immune responses by inducing ECAMs' expression. Ischemic insults can be separated into aglycemic and hypoxic components. However, whether aglycemia, hypoxia or OGD plays a major role in dysregulating BBB or promotes immune cell infiltration via ECAMs' expression is not clear. We investigated how expression of ICAM-1, VCAM-1, MAdCAM-1, PECAM-1, E- and P-selectin in response to TNF-alpha, IL-1beta and IFN gamma was altered by aglycemia (A), hypoxia (H) or combined oxygen glucose deprivation (OGD). METHODS: A cell surface enzyme linked immunoabsorbent assay (cell surface ELISA) was used to analyze ECAM expression. RESULTS: We observed that ICAM-1 and PECAM-1 expressions were insensitive to hypoxia, aglycemia or OGD. Conversely, VCAM-1 and E-selectin were increased by hypoxia, but not by aglycemia. MAdCAM-1 and P-selectin were induced by hypoxia, and decreased by aglycemia. Patterns of cytokine-regulated ECAMs' expression were also modified by metabolic conditions. CONCLUSIONS: Our results indicate that patterns of inflammation-associated ECAMs represent cumulative influences from metabolic stressors, as well as cytokine activation. The expression of ECAMs following tissue injury reflects mechanistic interactions between metabolic disturbances, and alterations in tissue cytokines. Normalization of tissue metabolism, as well as cytokine profiles, may provide important targets for therapeutic treatment of inflammation. PMID- 21981017 TI - Cumulative flying time and risk of venous thromboembolism. AB - The risk of venous thromboembolism (VTE) associated with cumulative flying time remains uncertain. In a case-control study in general practices throughout the UK, participants comprised 550 VTE cases identified from practice records and 1971 age- and gender-matched controls. Participants returned identical questionnaires asking for information including air travel details. Compared to not flying, cumulative flying time >12 h within the previous 4 weeks was associated with a threefold increase in the risk of VTE [odds ratio (OR) 2.75, 95% confidence interval (CI), 1.44-5.28]. Those who had flown >4 h in a single leg in the previous 4 weeks had twice the risk of VTE (OR 2.20, 95% CI, 1.29 3.73). These risks were no longer evident by 12 weeks and were similar to those of day-case or minor surgery (OR 5.35, 95% CI, 2.15-13.33). Equivalent risks for moderate and high-risk surgery were over 30-fold (OR 36.57, 95% CI, 13.05-102.52) and 140-fold (OR 141.71, 95% CI, 19.38-1036.01) respectively. The temporary nature of the association of cumulative and long-haul air travel with VTE suggests a causal relationship. The risks of VTE in those with a higher baseline risk due to surgery, previous VTE or obesity are further increased by air travel. PMID- 21981018 TI - A pilot study to investigate the effect of plate size on meal energy intake in normal weight and overweight/obese women. AB - BACKGROUND: Smaller plates are often recommended as a strategy for controlling energy intake; however, the effect of plate size on meal energy intake in normal weight compared to overweight or obese individuals is not known. The present study aimed to investigate this further. METHODS: Ten normal weight [mean (SD) body mass index, 21.7 (2.0) kg m(-2) ] and 10 overweight or obese [31.7 (3.6) kg m(-2) ] women attended a metabolic laboratory on two separate days for lunch. In this cross-over study, subjects were randomly assigned to eat lunch using either a small (21.6 cm) or a large (27.4 cm) plate. Each subject self-served spaghetti mixed with tomato sauce from an individual serving bowl onto the assigned plate, and ate until satisfied. The meal was consumed alone at a private table. During the second study day, each subject underwent the same procedure but used the alternate size plate. The amount eaten and energy consumed were calculated and a mixed effects analysis of variance model was used to compare energy intakes. RESULTS: Energy intakes using the small and large plate were 1356 (515) and 1365 (393) kJ, respectively, in normal weight subjects and 1314 (632) and 1226 (431) kJ, respectively, in overweight/obese subjects. Neither plate size, nor plate size by weight status significantly affected meal energy intake. There was no plate size by weight status effect on ratings of palatability, hunger, satiety, fullness or prospective consumption. CONCLUSIONS: Plate size did not affect energy intake from a single meal in either the normal weight or overweight/obese subjects. PMID- 21981019 TI - Evaluation of the occlusion vertical dimension of complete dentures after microwave disinfection. AB - OBJECTIVES: An increase in occlusal vertical dimension (OVD) after microwave disinfection may result in the need for adjustments in the complete dentures. This in vitro study evaluated the increase in OVD of maxillary complete dentures submitted to microwave disinfection protocols. MATERIAL AND METHODS: Thirty sets of complete dentures were evaluated as follows: Group 1-15 sets had the maxillary complete dentures submitted to microwave disinfection (650 W/3 min), once a week, for 4 weeks. Group 2-15 sets had the maxillary complete dentures submitted to microwave disinfection (650 W/3 min), three times a week, for 4 weeks. The vertical dimension was measured with a micrometre (in mm) before disinfection protocols (baseline readings) and after each week of disinfection. Data were analysed using Wilcoxon and Friedman tests (alpha = 0.05). RESULTS: For Group 1, no significant difference was found between the increases in OVD and zero, and no significant difference was found between the weeks. For Group 2, the increases in OVD were significantly greater than zero, and the Friedman test showed that weeks 3 and 4 had significantly greater changes than week 1 and that week 4 had significantly greater change than week 2. CONCLUSION: Microwave disinfection only promoted significant increase in OVD in Group 2, in which the values increased progressively. PMID- 21981021 TI - beta-Carotene and mineral content of different Chenopodium species and the effect of cooking on micronutrient retention. AB - In the present study, the beta-carotene, calcium, iron and zinc content in the leaves of 46 accessions of three Chenopodium species viz. Chenopodium album, C. album ssp. amaranticolor and Chenopodium quinoa was investigated. A wide range of variability, inter-specific as well as varietal, for the beta-carotene [0.19-5.91 mg 100 g(- 1) fresh weight (FW)], calcium (358.35-960.10 mg 100 g(- 1) FW), iron (0.56-7.90 mg 100 g(- 1) FW) and zinc content (0.07-4.26 mg 100 g(- 1) FW) was observed. The C. album ssp. amaranticolor accessions IC341710 and IC469275 had a high content of all the four nutrients and were ideal food to alleviate nutritional deficiencies in humans. Nutritionally rich IC341710 and IC469275 were further studied to estimate micronutrient retention in cooked leaves. Between the two methods used to cook leaves, stir-frying showed better retention of micronutrients than pressure cooking. PMID- 21981023 TI - Storage mites are the main sensitizers among adults in northern Vietnam: results from a population survey. PMID- 21981022 TI - The immunity-related GTPase Irgm3 relieves endoplasmic reticulum stress response during coxsackievirus B3 infection via a PI3K/Akt dependent pathway. AB - The IRG protein Irgm3 preserves cell survival during coxsackievirus B3 (CVB3) infection. However, the molecular mechanisms are not clear. Here, we examined the effect of Irgm3 expression on ER stress triggered by pharmacological agents or CVB3 infection. In Tet-On/Irgm3 HeLa cells, Irgm3 expression suppressed either chemical- or CVB3-induced upregulation of glucose-regulated protein 78. Further, Irgm3 strongly inhibited the activation of both the PERK and ATF6 pathways of ER stress responses, which further led to the diminished phosphorylation of eIF2alpha, reduced cleavage/activation of transcription factor SREBP1 and attenuated induction of proapoptotic genes CHOP and GADD34. These data were further supported by experiments using Irgm3 knockout mouse embryonic fibroblasts, in which the ER stress induced by CVB3 was not relieved due to the lack of Irgm3 expression. In addition, the tunicamycin-triggered ER stress promoted the subsequent CVB3 infection. The effect of Irgm3 on ER stress and CVB3 infection was diminished by the PI3K inhibitor, LY294002, while inhibitors of ERK, JNK and p38 had no effect. These data were further corroborated by transfection of cells with a dominant negative Akt. Taken together, these data suggest that Irgm3 relieves the ER stress response via a PI3K/Akt dependent mechanism, which contributes to host defence against CVB3 infection. PMID- 21981024 TI - Biophysical analysis of binding of WW domains of the YAP2 transcriptional regulator to PPXY motifs within WBP1 and WBP2 adaptors. AB - The YAP2 transcriptional regulator mediates a plethora of cellular functions, including the newly discovered Hippo tumor suppressor pathway, by virtue of its ability to recognize WBP1 and WBP2 signaling adaptors among a wide variety of other ligands. Herein, using isothermal titration calorimery and circular dichroism in combination with molecular modeling and molecular dynamics, we provide evidence that the WW1 and WW2 domains of YAP2 recognize various PPXY motifs within WBP1 and WBP2 in a highly promiscuous and subtle manner. Thus, although both WW domains strictly require the integrity of the consensus PPXY sequence, nonconsensus residues within and flanking this motif are not critical for high-affinity binding, implying that they most likely play a role in stabilizing the polyproline type II helical conformation of the PPXY ligands. Of particular interest is the observation that both WW domains bind to a PPXYXG motif with highest affinity, implicating a preference for a nonbulky and flexible glycine one residue to the C-terminal side of the consensus tyrosine. Importantly, a large set of residues within both WW domains and the PPXY motifs appear to undergo rapid fluctuations on a nanosecond time scale, suggesting that WW-ligand interactions are highly dynamic and that such conformational entropy may be an integral part of the reversible and temporal nature of cellular signaling cascades. Collectively, our study sheds light on the molecular determinants of a key WW-ligand interaction pertinent to cellular functions in health and disease. PMID- 21981025 TI - Mediation of vertebrate life histories via insulin-like growth factor-1. AB - Life-history traits describe parameters associated with growth, size, survival, and reproduction. Life-history variation is a hallmark of biological diversity, yet researchers commonly observe that one of the major axes of life-history variation after controlling for body size involves trade-offs among growth, reproduction, and longevity. This persistent pattern of covariation among these specific traits has engendered a search for shared mechanisms that could constrain or facilitate production of variation in life-history strategies. Endocrine traits are one candidate mechanism that may underlie the integration of life history and other phenotypic traits. However, the vast majority of this research has been on the effects of steroid hormones such as glucocorticoids and androgens on life-history trade-offs. Here we propose an expansion of the focus on glucocorticoids and gonadal hormones and review the potential role of insulin like growth factor-1 (IGF-1) in shaping the adaptive integration of multiple life history traits. IGF-1 is a polypeptide metabolic hormone largely produced by the liver. We summarize a vast array of research demonstrating that IGF-1 levels are susceptible to environmental variation and that IGF-1 can have potent stimulatory effects on somatic growth and reproduction but decrease lifespan. We review the few studies in natural populations that have measured plasma IGF-1 concentrations and its associations with life-history traits or other characteristics of the organism or its environment. We focus on two case studies that found support for the hypothesis that IGF-1 mediates adaptive divergence in suites of life-history traits in response to varying ecological conditions or artificial selection. We also examine what we view as potentially fruitful avenues of research on this topic, which until now has been rarely investigated by evolutionary ecologists. We discuss how IGF-1 may facilitate adaptive plasticity in life-history strategies in response to early environmental conditions and also how selection on loci controlling IGF-1 signaling may mediate population divergence and eventual speciation. After consideration of the interactions among androgens, glucocorticoids, and IGF-1 we suggest that IGF-1 be considered a suitable candidate mechanism for mediating life-history traits. Finally, we discuss what we can learn about IGF-1 from studies in free-ranging animals. The voluminous literature in laboratory and domesticated animals documenting relationships among IGF-1, growth, reproduction, and lifespan demonstrates the potential for a number of new research questions to be asked in free-ranging animals. Examining how IGF 1 mediates life-history traits in free-ranging animals could lead to great insight into the mechanisms that influence life-history variation. PMID- 21981026 TI - Graphene-based engine oil nanofluids for tribological applications. AB - Ultrathin graphene (UG) has been prepared by exfoliation of graphite oxide by a novel technique based on focused solar radiation. Graphene based engine oil nanofluids have been prepared and their frictional characteristics (FC), antiwear (AW), and extreme pressure (EP) properties have been evaluated. The improvement in FC, AW, and EP properties of nanofluids is respectively by 80, 33, and 40% compared with base oil. The enhancement can be attributed to the nanobearing mechanism of graphene in engine oil and ultimate mechanical strength of graphene. PMID- 21981027 TI - Effect of early EBV and/or CMV viremia on graft function and acute cellular rejection in pediatric liver transplantation. AB - BACKGROUND: The clinical impact of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections in the early post-transplantation period are poorly documented. We investigated the prevalence and timing of EBV and CMV infections during the first 21 d post-transplantation in relation to graft function and acute cellular rejection in a large cohort of pediatric liver transplantation recipients. PATIENTS AND METHODS: Clinical, biochemical, virological, and histopathological data of 62 consecutive children who received a liver transplant were reviewed retrospectively. RESULTS: Seventeen patients (27%) developed EBV and 11 (18%) CMV viremia (mean interval from surgery: 7.6 d, SD 3.6 and 8.7 d, SD 6.4, respectively). EBV and CMV viremia were more common as a consequence of reactivation than of primary infection. EBV viremic recipients had more often abnormal bilirubin levels [p = 0.01; OR 5.8: 95% CI 1.3-25.5]. Acute rejection was diagnosed in 20 recipients (32.3%). No correlation was found between rejection and EBV and CMV serology before transplantation and viremia after transplantation (mean interval between the diagnosis of rejection and the detection of EBV DNA and CMV DNA: one d, SD 4.4 and five d, SD 9.2, respectively). CONCLUSION: EBV and CMV viremia occur at a very early-stage post transplantation and do not appear to affect the short-term outcome of the transplant. PMID- 21981028 TI - Susceptibility of 100 filamentous fungi: comparison of two diffusion methods, Neo Sensitabs and E-test, for amphotericin B, caspofungin, itraconazole, voriconazole and posaconazole. AB - We compared the E-test method to that of the Neo-Sensitabs tablet diffusion assay for evaluating the in vitro susceptibility of 100 clinical isolates of filamentous fungi (Aspergillus spp., Fusarium spp., Scedosporium spp., zygomycetes and other molds) to amphotericin B, itraconazole, voriconazole, caspofungin, and posaconazole. We determined the categorical agreement level between E-test minimum inhibitory concentrations (MIC) and tablet end-points, as opposed to the following disagreement parameters: very major error - resistant parameter (R) in E-test and susceptible (S) in tablet; major error - S by E-test and R by tablet; minor error - shifts between S and susceptible dose-dependent (S DD) or S-DD and R. We also performed linear regression analyses and computed Pearson's correlation coefficients (R values) between the log transforms of MICs and the inhibition zone diameters of the five studied antifungal agents. For itraconazole we obtained 97% categorical agreement and R = -0.727. Categorical agreement for caspofungin and voriconazole was 96% and R =-0.821 and R = -0.789, respectively. For posaconazole the categorical agreement was 94% and R =-0.743. Amphotericin B exhibited a lower degree of agreement (76%, R = -0.672), especially in studies of Aspergillus spp. Our results suggest a potential value of the Neo-Sensitabs assay for in vitro susceptibility testing of molds to itraconazole, voriconazole, caspofungin and posaconazole, while amphotericin B exhibited an overall lower degree of agreement. PMID- 21981029 TI - KATP channel mutations in infants with permanent diabetes diagnosed after 6 months of life. AB - BACKGROUND/OBJECTIVE: Mutations in the K(ATP) channel genes are the commonest cause of permanent neonatal diabetes. Most patients obtain optimal glycemic control on sulfonylurea treatment. Genetic testing is currently recommended for all infants diagnosed before 6 months of age. We aimed to explore the prevalence of K(ATP) channel diabetes in infants presenting between 6 and 12 months. METHODS: The KCNJ11 and ABCC8 genes were sequenced in 115 infants with permanent diabetes diagnosed between 6 and 12 months and in 405 patients presenting before 6 months. RESULTS: Mutations in either gene were identified in 197 patients diagnosed before 6 months (48.6%), three infants diagnosed between 6 and 9 months (4.2%) and none of those diagnosed after 9 months. Two patients diagnosed after 6 months were successfully transferred from insulin to sulfonylureas. CONCLUSION: K(ATP) channel mutations are an uncommon cause of diabetes in infants presenting after 6 months. However, given the potential clinical benefit from identifying a K(ATP) channel mutation, we recommend that K(ATP) mutation testing should be routinely extended to infants diagnosed up to 9 months. PMID- 21981030 TI - Cell quality of apheresis-derived platelets treated with riboflavin-ultraviolet light after resuspension in platelet additive solution. AB - BACKGROUND: Previously, we evaluated the Mirasol pathogen reduction technology (PRT) system on platelet (PLT) function before resuspension. We now evaluated this system in the presence of PLT additive solution (PAS). STUDY DESIGN AND METHODS: Double-dose PLTs (n = 15) were generated using a commercially available apheresis system (Trima, Version 5.2, CaridianBCT) allowing for the resuspension in SSP+ (MacoPharma) immediately after collection. Paired units (n = 30) were PRT treated (M) or remained untreated (C) and analyzed for metabolism (pH, pO(2) , glucose, lactate, adenosine triphosphate [ATP]), swirl, hypotonic shock response (HSR), turbidometric aggregation, CD62P expression, annexin A5 and lactate dehydrogenase (LDH) release, mitochondrial enzymatic reduction activity (MTS), transmembrane mitochondrial potential (Deltapsi), and surface coverage (SC) during shear-induced adhesion throughout 8 days of storage. RESULTS: As seen previously, PRT treatment of PLT units, containing a mean of 3.9 * 10(11) +/- 0.3 * 10(11) PLTs in 397 +/- 10 mL with a 32% to 34% plasma carryover, was associated with significantly (p < 0.001) increased cell activation, acidity, and glycolytic flux. PRT treatment appeared to up regulate both oxidative pathway and adhesional properties as evidenced by significantly higher MTS reduction, oxygen consumption, and shear-induced SC on Day 1 (p <= 0.016). While no significant differences were found for LDH release and ATP content (except for Day 8), M units were significantly inferior (p <= 0.021) for aggregation (TRAP-6); for Deltapsi and annexin A5 release (by Day 5); and for swirl, HSR, and MTS reduction (by Day 7). CONCLUSION: PRT treatment in the presence of PAS was comparable to PRT treatment before resuspension preserving ATP content and mitochondrial function. PMID- 21981032 TI - Disentangling the roles of natural selection and genetic drift in shaping variation at MHC immunity genes. AB - The major histocompatibility complex (MHC) forms an integral component of the vertebrate immune response and, due to strong selection pressures, is one of the most polymorphic regions of the entire genome. Despite over 15 years of research, empirical studies offer highly contradictory explanations of the relative roles of different evolutionary forces, selection and genetic drift, acting on MHC genes during population bottlenecks. Here, we take a meta-analytical approach to quantify the results of studies into the effects of bottlenecks on MHC polymorphism. We show that the consequences of selection acting on MHC loci prior to a bottleneck event, combined with drift during the bottleneck, will result in overall loss of MHC polymorphism that is ~15% greater than loss of neutral genetic diversity. These results are counter to general expectations that selection should maintain MHC polymorphism, but do agree with the results of recent simulation models and at least two empirical studies. Notably, our results suggest that negative frequency-dependent selection could be more important than overdominance for maintaining high MHC polymorphism in pre-bottlenecked populations. PMID- 21981031 TI - Generation of reactive oxygen species in adipose-derived stem cells: friend or foe? AB - INTRODUCTION: Reactive oxygen species (ROS) participate in cellular apoptosis and are involved in pathophysiological etiology of degenerative diseases. However, recent studies suggest that ROS at low levels may play a pivotal role as second messengers and activate normal cellular processes. Intracellular ROS increase the proliferation, migration, and regenerative potential of adipose-derived stem cells (ASCs). In contrast, manipulations that diminish intracellular ROS levels interfere with normal ASC function. ROS generation therefore acts like a double edged sword. AREAS COVERED: This review discusses the following research questions: i) Do ROS stimulate or suppress ASCs? ii) How are ROS generated from ASCs? iii) Which function(s) is/are regulated by intracellular ROS generation? In addition, the antioxidant/antiapoptotic effect of ASCs is briefly introduced. EXPERT OPINION: Whether ROS is harmful or beneficial is primarily a question of dosage. Low or moderate ROS generation increases the proliferation, migration and regenerative potential of ASCs. Therefore, it is beneficial to expose ASCs to moderate oxidative stress during manipulation. The addition of a ROS donor in culture can reduce the cost for the expansion of ASCs and a ROS preconditioning can enhance the regenerative potential of ASCs. PMID- 21981036 TI - Synthesis and decarbonylation reactions of the triiron phosphinidene complex [Fe3Cp3(MU-H)(MU3-PPh)(CO)4]: easy cleavage and formation of P-H and Fe-Fe bonds. AB - The binuclear phosphine complex [Fe(2)Cp(2)(MU-CO)(2)(CO)(PH(2)Ph)] (Cp = eta(5) C(5)H(5)) reacted with the acetonitrile adduct [Fe(2)Cp(2)(MU-CO)(2)(CO)(NCMe)] in dichloromethane at 293 K to give the trinuclear hydride-phosphinidene derivative [Fe(3)Cp(3)(MU-H)(MU(3)-PPh)(CO)(4)] as a mixture of cis,anti and trans isomers (Fe-Fe = 2.7217(6) A for the cis,anti isomer). In contrast, photochemical treatment of the phosphine complex with [Fe(2)Cp(2)(CO)(4)] gave the phosphide-bridged complex trans-[Fe(3)Cp(3)(MU-PHPh)(MU-CO)(2)(CO)(3)] as the major product, along with small amounts of the binuclear hydride-phosphide complexes [Fe(2)Cp(2)(MU-H)(MU-PHPh)(CO)(2)] (cis and trans isomers), which are more selectively prepared from [Fe(2)Cp(2)(CO)(4)] and PH(2)Ph at 388 K. The photochemical decarbonylation of either of the mentioned triiron compounds led reversibly to three different products depending on the reaction conditions: (a) the 48-electron phosphinidene cluster [Fe(3)Cp(3)(MU-H)(MU(3)-PPh)(MU-CO)(2)] (Fe Fe = 2.592(2)-2.718(2) A); (b) the 50-electron complex [Fe(3)Cp(3)(MU-H)(MU(3) PPh)(MU-CO)(CO)(2)], also having carbonyl- and hydride-bridged metal-metal bonds (Fe-Fe = 2.6177(3) and 2.7611(4) A, respectively); and (c) the 48-electron phosphide cluster [Fe(3)Cp(3)(MU-PHPh)(MU(3)-CO)(MU-CO)(2)], an isomer of the latter phosphinidene complex now having three intermetallic bonds (Fe-Fe = 2.5332(8)-2.6158(8) A). PMID- 21981034 TI - Can perceptual learning be used to treat amblyopia beyond the critical period of visual development? AB - BACKGROUND: Amblyopia presents early in childhood and affects approximately 3% of western populations. The monocular visual acuity loss is conventionally treated during the 'critical periods' of visual development by occluding or penalising the fellow eye to encourage use of the amblyopic eye. Despite the measurable success of this approach in many children, substantial numbers of people still suffer with amblyopia later in life because either they were never diagnosed in childhood, did not respond to the original treatment, the amblyopia was only partially remediated, or their acuity loss returned after cessation of treatment. PURPOSE: In this review, we consider whether the visual deficits of this largely overlooked amblyopic group are amenable to conventional and innovative therapeutic interventions later in life, well beyond the age at which treatment is thought to be effective. RECENT FINDINGS: There is a considerable body of evidence that residual plasticity is present in the adult visual brain and this can be harnessed to improve function in adults with amblyopia. Perceptual training protocols have been developed to optimise visual gains in this clinical population. Results thus far are extremely encouraging; marked visual improvements have been demonstrated, the perceptual benefits transfer to new visual tasks and appear to be relatively enduring. The essential ingredients of perceptual training protocols are being incorporated into video game formats, facilitating home-based interventions. SUMMARY: Many studies support perceptual training as a tool for improving vision in amblyopes beyond the critical period. Should this novel form of treatment stand up to the scrutiny of a randomised controlled trial, clinicians may need to re-evaluate their therapeutic approach to adults with amblyopia. PMID- 21981037 TI - The consultation and relational empathy measure: an investigation of its scaling structure. AB - PURPOSE: The Consultation and Relational Empathy (CARE) measure is recommended to evaluate the quality of care. However, there is no evidence that it is valid in rehabilitation. Aims were to examine the internal construct (factorial) validity of the CARE in the assessment of the patient-therapist relationship. METHOD: CARE data were part of an experimental study of acupuncture and different currently used acupuncture placebo controls, including 213 patients (age 66.8, SD 8.3, 58% female) with chronic stable hip or knee pain of mechanical origin, waiting for a joint replacement. CARE was completed two weeks into the study and on completion, two weeks later. DATA ANALYSIS: Cronbach alpha, factor analysis and Rasch analysis. RESULTS: Internal construct validity was supported (82% of variance explained by the first factor; fit to the Rasch model chi(2) = 18.2, P = 0.57). CARE was unidimensional, had local independence of items, good item fit, absence of Differential Item Functioning and invariance over time. Three percent of people did not complete items 9 & 10. CONCLUSIONS: CARE satisfied strict criteria for internal construct validity. An interval scale transformation is available that can be used in clinical practice and research. Further work is required to investigate item non-response and how this may be dealt with in clinical settings. PMID- 21981038 TI - Effects of high hydrostatic pressure on some functional and nutritional properties of soy protein isolate for infant formula. AB - The effects and mechanism of high hydrostatic pressure (HHP) on some functional and nutritional properties of soy protein isolate (SPI) for infant formula were investigated. Results indicated that solubility, water holding capacity, emulsification activity index, and foaming capacity were improved at lower pressure and time levels, whereas these properties declined at higher levels. However, the emulsification stability index dropped when the pressure increased and the foaming stability decreased with pressure and time levels rising. HHP treated SPI gave better swallowing properties and in vitro digestibility than control. The hardness, adhesive force, and springiness of SPI gels increased with increaded pressure and elongated time, being lower than those of the control. Near UV circular dichroism spectra confirmed the alteration of tertiary and/or quaternary conformations caused by HHP. Sodiumdoecyl sulfate polyacrylamide gel electrophoresis results indicated that beta-conglycinin was more pressure labile than glycinin, and high molecular weight subunits formed via disulfide linkage at higher treatment levels. PMID- 21981042 TI - Effects of SIRT6 silencing on collagen metabolism in human dermal fibroblasts. AB - SIRT6 (sirtuin 6) has been identified as an anti-aging protein, and SIRT6 deficient mice display numerous progeroid and aging-like phenotypes. However, there are no reports correlating skin aging with SIRT6. To explore how SIRT6 affects collagen metabolism and determine its role in skin aging, the levels of COL1A1 (type I collagen), COL3A1 (type III collagen) and TGFbeta1 (transforming growth factor beta1) mRNA expression were detected by RT-Q-PCR (real-time quantitative PCR), and MMP1 (matrix metalloproteinase 1) concentration in HDF (human dermal fibroblast) supernatants was determined by ELISA after blocking SIRT6 using siRNA (small interefering RNA). Compared with the control group, blocking SIRT6 significantly decreased the HC (hydroxyproline content). SIRT6 knockdown in HDFs inhibited the transcription of COL1A1 and prompted MMP1 secretion, but had no effect on COL3A1 and TGFbeta1. Furthermore, NF-kappaB p65 (nuclear factor kappaB p65) protein in the nucleus was increased after blocking SIRT6. The results suggest that SIRT6 knockdown in HDFs influence the synthesis and degradation of collagen by hyperactive NF-kappaB signalling, which leads to a decrease in dermal collagen fibrils. SIRT6 may therefore play an important role in the process of skin anti-aging. PMID- 21981043 TI - Very elderly patients with essential thrombocythaemia: are they a separate category? A monocentric study on 118 patients older than 75 years. PMID- 21981044 TI - Changes in oestrogen receptor-beta mRNA expression in male rat brain with age. AB - Oestrogen has important roles not only in the regulation of reproductive function, but also with respect to other functions, such as cognition, emotion and cardiovascular regulation. Oestrogen acts mainly via its oestrogen receptor (ER), namely, ERalpha and ERbeta in target tissues, including the brain. During ageing, the actions of oestrogen are altered in both females and males, raising the possibility that the expression level of ER may be altered with age. Age related changes in ER expression in female rat brain have been well demonstrated with regard to reproductive ageing, whereas very little is known about the effects of age on the expression of ERs, especially ERbeta, in males. In the present study, which aimed to elucidate the effects of ageing on ERbeta expression in the male brain at the transcriptional level, we performed in situ hybridisation using young (10weeks), middle-aged (12months) and old (24 months) gonadally-intact male rats. We revealed a wide distribution of ERbeta mRNA positive cells throughout the brain, and found that the number of ERbeta mRNA positive cells was reduced in several brain regions in males with ageing. ERbeta mRNA-positive cells were decreased with age in layer 6 of the cerebral cortex, hippocampal CA1/CA3 regions, the dorsal endopiriform nucleus, the medial septal nucleus, various subregions of the amygdala (central, lateral, anterior cortical and posterolateral cortical subnuclei), the anteroventral periventricular nucleus, the substantia nigra pars compacta, the raphe magnus nucleus and the locus coeruleus. These results suggest that ERbeta expression in male rat brain decreases with age at the transcriptional level and that these ageing effects are region-specific. PMID- 21981045 TI - Phosphorylation of Marburg virus matrix protein VP40 triggers assembly of nucleocapsids with the viral envelope at the plasma membrane. AB - Marburg virus (MARV) matrix protein VP40 plays a key role in virus assembly, recruiting nucleocapsids and the surface protein GP to filopodia, the sites of viral budding. In addition, VP40 is the only MARV protein able to induce the release of filamentous virus-like particles (VLPs) indicating its function in MARV budding. Here, we demonstrated that VP40 is phosphorylated and that tyrosine residues at positions 7, 10, 13 and 19 represent major phosphorylation acceptor sites. Mutagenesis of these tyrosine residues resulted in expression of a non phosphorylatable form of VP40 (VP40(mut) ). VP40(mut) was able to bind to cellular membranes, produce filamentous VLPs, and inhibit interferon-induced gene expression similarly to wild-type VP40. However, VP40(mut) was specifically impaired in its ability to recruit nucleocapsid structures into filopodia, and released infectious VLPs (iVLPs) had low infectivity. These results indicated that tyrosine phosphorylation of VP40 is important for triggering the recruitment of nucleocapsids to the viral envelope. PMID- 21981046 TI - Influence of different mucosal resiliency and denture reline on stress distribution in peri-implant bone tissue during osseointegration. A three dimensional finite element analysis. AB - OBJECTIVE: The aim of this study was to evaluate the influence of mucosal properties and relining material on the stress distribution in peri-implant bone tissue during masticatory function with a conventional complete denture during the healing period through finite element analysis. MATERIALS AND METHODS: Three dimensional models of a severely resorbed mandible with two recently placed implants in the anterior region were created and divided into the following situations: (i) conventional complete denture and (ii) relined denture with soft lining material. The mucosal tissue properties were divided into soft, resilient and hard. The models were exported to mechanical simulation software; two simulations were carried out with a load at the lower right canine (35 N) and the lower right first molar (50 N). Data were qualitatively evaluated using Maximum Principal Stress, in MPa, given by the software. RESULTS: All models showed stress concentrations in the cortical bone corresponding to the cervical part of the implant. The mucosal properties influenced the stress in peri-implant bone tissue showing a different performance according to the denture base material. The simulations with relined dentures showed lower values of stress concentration than conventional ones. CONCLUSIONS: It seems that the mucosal properties and denture reline have a high influence on the stress distribution in the peri implant bone during the healing period. PMID- 21981047 TI - Methyl salicylate: a reactive chemical warfare agent surrogate to detect reaction with hypochlorite. AB - Methyl salicylate (MeS) has a rich history as an inert physical simulant for the chemical warfare agents sulfur mustard and soman, where it is used extensively for liquid- and vapor-permeation testing. Here we demonstrate possible utility of MeS as a reactivity simulant for chlorine-based decontaminants. In these experiments MeS was reacted with sodium hypochlorite varying stoichiometry, temperature, reaction time, and pH. No colored oxidation products were observed; however, chlorination of the aromatic ring occurred ortho (methyl 3 chlorosalicylate) and para (methyl 5-chlorosalicylate) to the position bearing the -OH group in both the mono- and disubstituted forms. The monosubstituted para product accumulated initially, and the ortho and 3,5-dichloro products formed over the next several hours. Yields from reactions conducted below pH 11 declined rapidly with decreasing pH. Reactions run at 40 degrees C produced predominantly para substitution, while those run at 0 degrees C produced lower yields of ortho and para-substituted products. Reactions were also carried out on textile substrates of cotton, 50/50 nylon-cotton, and a meta aramid. The textile data broadly reproduced reaction times and stoichiometry observed in the liquid phase, but are complicated by physical and possibly chemical interactions with the fabric. These data indicate that, for hypochlorite-containing neutralizing agents operating at strongly alkaline pH, one can expect MeS to react stoichiometrically with the hypochlorite it encounters. This suggests utility of MeS in lieu of such highly hazardous surrogates as monochloroalkyl sulfides as a simulant for threat scenarios involving the stoichiometric decomposition of sulfur mustard. Specifically, the extent of coverage of the simulant on a fabric by the neutralizing agent can be directly measured. Similar reactivity toward other halogen oxidizing agents is likely but remains to be demonstrated. PMID- 21981048 TI - The relationship between obesity and hypoferraemia in adults: a systematic review. AB - A growing number of studies suggest a potential link between obesity and altered iron metabolism. The purpose of this systematic review was to examine existing literature on iron status in obese populations. A comprehensive literature search was conducted. Included studies recruited participants >= 18 years with a body mass index >= 30 kg m(-2) and provided descriptive statistics for haemoglobin or ferritin at a minimum. There were 25 studies meeting all eligibility criteria, of these 10 examined iron status in free-living obese individuals and 15 reported baseline iron biomarkers from bariatric surgery candidates. Non-obese comparison groups were used by 10 (40%) articles. In these, seven obese groups reported higher mean haemoglobin concentration; six reported significantly higher ferritin concentration; and four significantly lower transferrin saturation. Due to insufficient data, it was not possible to make conclusions regarding mean differences for soluble transferrin receptor (sTfR), hepcidin or C-reactive protein. Existing evidence suggests a tendency for higher haemoglobin and ferritin concentration and lower transferrin saturation in obesity. Alternation of iron biomarkers in obese populations may be a result of obesity-related inflammation and/or related comorbidities. Further research incorporating measurement of inflammatory cytokines, sTfR and hepcidin is required to confirm the impact of obesity on iron status. PMID- 21981058 TI - Essential, but at what risk? A prospective study on central venous access in patients with haematological malignancies. AB - AIMS: Central venous catheters (CVC) are integral to modern haematology practice; however, they are associated with a range of complications. This prospective study aimed to determine the rate of CVC-related complications and risk factors in haematology patients, who are vulnerable because of their underlying pathology and treatments. METHODS: All inpatients that had a non-tunnelled CVC inserted in a 14-month period in the haematology ward at St Vincent's Hospital were enrolled. Complications (immediate and late), demographics, type of device, insertion technique and duration of dwell, were examined using multivariate analysis. RESULTS: One hundred and seventy-four CVC in 84 patients were recorded, representing 3016 catheter-days. At least one complication was found in 43 (24.7%) patients. Immediate complications occurred in 13 (7.5%) insertions, with a higher rate in those inserted after >=2 attempts compared with one (P = 0.02). Catheter-related bloodstream infection occurred at a rate of 7.6 per 1000 catheter-days, with acute lymphoblastic leukaemia associated with a higher rate (P = 0.02), and subclavian vein CVC had a lower rate compared with other locations (P < 0.01). Thrombosis was found in seven (4.0%) patients, with subclavian CVC carrying an increased risk (P = 0.02). CONCLUSIONS: This prospective observational study found almost a quarter of haematology patients experience a CVC-related complication. An association was found with a number of attempts at insertion and immediate complications; other risk factors included anatomical location, underlying disease and duration of catheterisation. The relatively high complication rate, compared with reports of non-haematology patients, highlights the need to improve CVC management, a vital part of care for this population. PMID- 21981059 TI - PEST-domain-enriched tyrosine phosphatase and glucocorticoids as regulators of anaphylaxis in mice. AB - BACKGROUND: PEST-domain-enriched tyrosine phosphatase (PEP) is a protein tyrosine phosphatase exclusively expressed in hematopoietic cells. It is a potent negative regulator of T-cell receptor signalling that acts on receptor-coupled protein tyrosine kinases. PEST-domain-enriched tyrosine phosphatase is also expressed in mast cell and is positively regulated by glucocorticoids, but its function is unknown. In this communication, the function of PEP is analysed in mast cells. METHODS: Signal transduction cascades following IgE receptor cross-linking were compared in bone marrow-derived mast cells (BMMC) from PEP(-/-) and PEP(+/+) mice. Furthermore, antigen-induced passive systemic anaphylaxis (PSA) was analysed in PEP(+/+) and PEP(-/-) mice. RESULTS: Bone marrow-derived mast cells from PEP(-/-) mice showed impaired PLCgamma1 phosphorylation and Ca(2+) mobilization. Additionally, mice deficient in PEP showed impaired mast cell degranulation and were less susceptible to PSA. Treatment of wild-type BMMC or mice with an Au(I)-phosphine complex that selectively inhibits PEP activity produced defects in Ca(2+) signalling pathway and reduced anaphylaxis similar to that caused by the deletion of the PEP gene. Glucocorticoid that negatively regulates a wide range of mast cell action increased PEP expression and only partially inhibited anaphylaxis. However, glucocorticoid potently inhibited anaphylaxis when combined with the PEP inhibitor. CONCLUSIONS: PEST-domain enriched tyrosine phosphatase is an important positive regulator of anaphylaxis. Pharmacological inhibition of its activity together with glucocorticoid administration provide an effective rescue for PSA in mice. PMID- 21981060 TI - Effects of long-term use of antiretroviral therapy on the prevalence of oral Epstein-Barr virus. AB - BACKGROUND: The objectives of this study were to determine (i) the prevalence of oral Epstein-Barr virus (EBV) in HIV-infected subjects compared to non-HIV controls and (ii) the effects of long-term use of antiretroviral therapy (ART) on the prevalence of oral EBV. METHODS: A cross-sectional study was performed in HIV infected subjects with and without ART, and non-HIV individuals. DNA in saliva samples was extracted and used as a template to detect EBV BamH1W and EBNA1 by quantitative polymerase chain reaction. Student t-test and ANOVA test were performed to determine the prevalence rates among groups. RESULTS: Forty-nine HIV infected subjects: 37 on ART (age range 23-54 year, mean 37 year), 12 not on ART (age range 20-40 year, mean 31 year), and 20 non-HIV controls (age range 19-53 year, mean 31 year) were enrolled. The numbers of EBV BamH1W in saliva were found to be significantly higher in HIV-infected subjects than non-HIV controls (80% vs. 20%, mean = 12118 vs. 134 copies/10(5) cells, P < 0.001). HIV-infected subjects who were on ART had significantly lower numbers of EBV BamH1W than those who were not (mean = 4102 vs. 138613 copies/10(5) cells, P = 0.011). The numbers were significantly lower in those who received long-term ART compared with short term (mean = 1401 vs. 11124 copies/10(5) cells, P = 0.034). No significant difference was observed between the groups when using EBNA1 primers. CONCLUSIONS: Prevalence of oral EBV was significantly higher in HIV-infected subjects than non HIV-controls. The numbers of the virus were significantly decreased by ART. Long term use of ART did not increase oral EBV. PMID- 21981061 TI - Acetic acid-enhanced chromoendoscopy is more cost-effective than protocol-guided biopsies in a high-risk Barrett's population. AB - To examine the efficacy and potential cost implications of acetic acid (AA) chromoendoscopy in the assessment of Barrett's neoplasia. Our prospective database of patients referred between 2005 and 2010 with suspected early neoplasia was reviewed. High-resolution Fujinon gastroscopes and EPX-4400 processor were used. Inspection of Barrett's neoplasia was carried out using white light followed by AA. Neoplastic areas were noted, and targeted biopsy was carried out. This was followed by quadrantic biopsies of the remaining Barrett's neoplasia. The cost of protocol-guided biopsies was compared with AA-guided biopsy protocols. Two hundred sixty-three procedures on 197 patients were examined. High-risk neoplasia was found during 143 procedures. In 96% of cases it was identified with AA. The cost of histological evaluation by Cleveland protocol would be L139,416.30. The cost by AA-targeted biopsy followed by random biopsies in one pot would be L25,032.50. For AA-targeted biopsies alone the cost would be L9,541.8 but results in a 4% miss rate. AA localizes neoplastic lesions in the majority of patients and could potentially represent a significant cost saving in patients with suspected neoplasia. PMID- 21981063 TI - Congenital goitrous hypothyroidism: mutation analysis in the thyroid peroxidase gene. AB - BACKGROUND: Iodide organification defect (IOD) is characterized by a reduced ability of the thyroid gland to retain iodide resulting in hypothyroidism. Mutations in thyroid peroxidase (TPO) gene appear to be the most common cause of IOD and are commonly inherited in an autosomal recessive fashion. The TPO gene is located on the chromosome 2p25. It comprises 17 exons, covers approximately 150 kb of genomic DNA and codes 933 amino acids. OBJECTIVES: In this study, we characterize the clinical and molecular basis of seven patients from four unrelated families with congenital hypothyroidism (CH) because of IOD. DESIGN AND METHODS: All patients underwent clinical, biochemical and imaging evaluation. The promoter and the complete coding regions of the human TPO along with the flanking intronic regions were analysed by single-strand conformation polymorphism analysis and direct DNA sequencing. Segregation analysis of mutations was carried out, and the effect of the novel missense identified mutations was investigated by 'in silico' studies. RESULTS: All subjects had congenital and persistent primary hypothyroidism. Three novel mutations: c.796C>T [p.Q266X], c.1784G>A [p.R595K] and c.2000G>A [p.G667D] and a previously reported mutation: c.1186_1187insGGCC [p.R396fsX472] have been identified. Four patients were compound heterozygous for p.R396fsX472/p.R595K mutations, two patients were homozygous for p.R595K, and the remaining patient was a compound heterozygous for p.Q266X/p.G667D. CONCLUSIONS: Our findings confirm the genetic heterogeneity of TPO defects and the importance of the implementation of molecular studies to determinate the aetiology of the CH with dyshormonogenesis. PMID- 21981064 TI - Molecular survey of concrete sewer biofilm microbial communities. AB - The microbial composition of concrete biofilms within wastewater collection systems was studied using molecular assays. SSU rDNA clone libraries were generated from 16 concrete surfaces of manholes, a combined sewer overflow, and sections of a corroded sewer pipe. Of the 2457 sequences analyzed, alpha-, beta-, gamma-, and delta-Proteobacteria represented 15%, 22%, 11%, and 4% of the clones, respectively. beta-Proteobacteria (47%) sequences were more abundant in the pipe crown than any of the other concrete surfaces. While 178 to 493 Operational Taxonomic Units (OTUs) were associated with the different concrete samples, only four sequences were shared among the different clone libraries. Bacteria implicated in concrete corrosion were found in the clone libraries while archaea, fungi, and several bacterial groups were also detected using group-specific assays. The results showed that concrete sewer biofilms are more diverse than previously reported. A more comprehensive molecular database will be needed to better study the dynamics of concrete biofilms. PMID- 21981065 TI - Service needs and service gaps among refugees with disabilities resettled in the United States. AB - PURPOSE: To examine the adequacy of existing service systems in addressing the needs of refugees with disabilities resettled in the U.S.A. METHODS: A cross disability group of eight Cambodian and seven Somali refugees were purposively selected to participate in a 2-year qualitative study in the Midwestern U.S.A. Ten disability/refugee service providers and key experts on refugee resettlement were also recruited to participate. Data sources included in-depth interviews, focus groups, participant observations and social network surveys with disabled refugees. Participant observations and semi-structured interviews were also conducted with service providers and key experts. Data were analyzed using coding procedures based on a grounded theory approach. RESULTS: Disabled refugee participants experienced several unmet disability-related needs and limited access to resettlement resources on account of their disability. These findings were associated with refugee service providers having limited awareness of disability rights and resources and a narrow biomedical perspective of disability. Additionally there was a disconnection between refugee and disability service systems resulting from resource limitations within agencies, mistrust between the different service entities, and a lack of cross-cultural nuance among disability service organizations. These findings contribute important insights to the literature on disability disparities. CONCLUSIONS: Disabled refugees resettled in the U.S.A. have many unmet needs associated with gaps in-service delivery stemming from disconnections between refugee and disability service systems. PMID- 21981066 TI - Solvent induced diverse dimensional coordination assemblies of cupric benzotriazole-5-carboxylate: syntheses, crystal structures, and magnetic properties. AB - Three cupric coordination assemblies [Cu(btca)(H(2)O)(2)] (1), [Cu(btca)(H(2)O)(3.5)](8).16H(2)O (2), and [Cu(2.5)(btca)(1.5)(Hbtca)(0.5)(MU Cl)(0.5)(MU(3)-OH)(H(2)O)].H(2)O (3) have been solvothermally synthesized by cupric salts and a bifunctional ligand benzotriazole-5-carboxylic acid (H(2)btca) in different solvent medium. These complexes were structurally characterized by X ray diffraction analyses and further identified by infrared spectra (IR), elemental analyses, powder X-ray diffraction (PXRD), and thermogravimetric analyses (TGA). Single crystal structural analysis shows that these coordination compounds assembled by the almost same reactants present diverse dimensional crystal structures, wherein 1 possesses two-dimensional (2D) layers with (4.8(2)) topology, the zero-dimensional (0D) neutral metallomacrocycle with flat octagonal geometry in 2 connects each other through hydrogen bonding to extend to be a three-dimensional (3D) nanotubular network, and 3 exhibits 3D framework with 1D honeycomb channels constructed by the strip-shaped chains containing [Cu(5)(MU(3) OH)(2)(btca)(4)](-) pentaclusters bridging to the adjacent Cu(6)(btca)(12)(6-) cages. The diversity of these structures mainly stems from the versatile coordination modes of the anionic ligand in each compound, especially the 1,2,3 triazolate group: bidentate MU(1,2) bridging mode in 1, bidentate MU(1,3) bridging mode in 2, and tridentate MU(1,2,3) bridging mode in 3, respectively. Furthermore, the magnetic properties of 1-3 have been investigated as well. PMID- 21981067 TI - Fragmentation can increase spatial genetic structure without decreasing pollen mediated gene flow in a wind-pollinated tree. AB - Fragmentation reduces population sizes, increases isolation between habitats and can result in restricted dispersal of pollen and seeds. Given that diploid seed dispersal contributes more to shaping fine-scale spatial genetic structure (SGS) than haploid pollen flow, we tested whether fine-scale SGS can be sensitive to fragmentation even if extensive pollen dispersal is maintained. Castanopsis sclerophylla (Lindley & Paxton) Schottky (Fagaceae), a wind-pollinated and gravity seed-dispersed tree, was studied in an area of southeast China where its populations have been fragmented to varying extents by human activity. Using different age classes of trees in areas subject to varying extents of fragmentation, we found no significant difference in genetic diversity between prefragmentation vs. postfragmentation C. sclerophylla subpopulations. Genetic differentiation among postfragmentation subpopulations was also only slightly lower than among prefragmentation subpopulations. In the most fragmented habitat, selfing rates were significantly higher than zero in prefragmentation, but not postfragmentation, cohorts. These results suggest that fragmentation had not decreased gene flow among these populations and that pollen flow remains extensive. However, significantly greater fine-scale SGS was found in postfragmentation subpopulations in the most fragmented habitat, but not in less fragmented habitats. This alteration in SGS reflected more restricted seed dispersal, induced by changes in the physical environments and the prevention of secondary seed dispersal by rodents. An increase in SGS can therefore result from more restricted seed dispersal, even in the face of extensive pollen flow, making it a sensitive indicator of the negative consequences of population fragmentation. PMID- 21981068 TI - Studies on the key aroma compounds in soy milk made from three different soybean cultivars. AB - An investigation by aroma extract dilution analysis (AEDA) of the aroma concentrate of soy milk made from a major Japanese soybean cultivar, Fukuyutaka (FK), revealed 20 key aroma compounds having flavor dilution (FD) factors of not less than 64. Among them, 2-isopropyl-3-methoxypyrazine, cis-4,5-epoxy-(E)-2 decenal, trans-4,5-epoxy-(E)-2-decenal, 3-hydroxy-4,5-dimethyl-2(5H)-furanone, and 2'-aminoacetophenone were identified as the key aroma compounds in soy milk for the first time. (E,E)-2,4-Decadienal exhibiting a fatty note and trans-4,5 epoxy-(E)-2-decenal exhibiting a metallic/sweet note were detected as having the highest FD factors of 4096, followed by hexanal (green), (E)-2-nonenal (fatty), and (E,E)-2,4-nonadienal (fatty) having FD factors of 1024. Although all of these compounds might be generated from lipids, various aroma components, which were thought to be generated from amino acids, sugars, and ferulic acid, were detected having FD factors of 64-256. Investigation by comparative AEDA experiments of the soy milk aroma concentrates of two cultivars for soybean curd and soy milk, FK and Vinton81 (VT), and one cultivar for boiled beans, Miyagishirome (MY), revealed that most of the key aroma compounds were common to all of them, but 2 isopropyl-3-methoxypyrazine, exhibiting a pea-like/earthy note, was detected only in FK and VT. In addition, a sensory experiment revealed that the pea-like/earthy notes in FK and VT were significantly stronger than that in MY. These results demonstrated that a pea-like/earthy note contributed by 2-isopropyl-3 methoxypyrazine might be one of the essential characteristics to describe soy milk aromas. PMID- 21981074 TI - Structure of peptides on metal oxide surfaces probed by NMR. AB - Peptides that bind inorganic surfaces and template the formation of nanometer sized inorganic particles are of great interest for the self- or directed assembly of nanomaterials for sensors and diagnostic applications. These surface recognizing peptides can be identified from combinatorial phage-display peptide libraries, but little experimental information is available for understanding the relationship between the peptide sequence, structure at the nanoparticle surface, and function. We have developed NMR methods to determine the structures of peptides bound to inorganic nanoparticles and report on the structure of three peptides bound to silica and titania surfaces. Samples were prepared under conditions leading to rapid peptide exchange at the surface such that solution based nuclear Overhauser experiments can be used to determine the three dimensional structure of the bound peptide. The binding motif is defined by a compact "C"-shaped structure for the first six amino acids in the 12-mer. The orientation of the peptide on the nanoparticle surface was determined by magnetization transfer from the nanoparticle surface to the nearby peptide protons. These methods can be applied to a wide variety of abiotic interfaces to provide an insight into the relationship between the primary sequence of peptides and their functionality at the interface. PMID- 21981075 TI - What monozygotic twins discordant for phenotype illustrate about mechanisms influencing genetic forms of neurodegeneration. AB - As monozygotic (MZ) twins are believed to be genetically identical, discordance for disease phenotype between MZ twins has been used in genetic research to understand the contribution of genetic vs environmental factors in disease development. However, recent studies show that MZ twins can differ both genetically and epigenetically. Screening MZ twins for genetic and/or epigenetic differences could be a useful and novel approach to identify modifying factors influencing phenotypic expression of disease. MZ twins that are phenotypically discordant for monogenic diseases are of special interest. Such occurrences have been described for Huntington's disease, spinocerebellar ataxias, as well as for familial forms of Alzheimer's disease. By comparing MZ twins that are phenotypically discordant, crucial factors influencing the phenotypic expression of the disease could be identified, which may be of relevance for understanding disease pathogenesis and variability in disease phenotype. Overall, understanding the crucial factors in development of a neurodegenerative disorder will have relevance for predictive testing, preventive treatment and could help to identify novel therapeutic targets. PMID- 21981076 TI - Anatomically-specific actions of oestrogen receptor in the developing female rat brain: effects of oestradiol and selective oestrogen receptor modulators on progestin receptor expression. AB - Steroid hormones largely exert their actions by activating nuclear receptors, which, as transcription factors, powerfully influence fundamental processes of neural development. Often, steroid receptor action demonstrates remarkable specificity under different developmental, anatomical or hormonal conditions. Yet, the mechanisms underlying such specificity are poorly understood. The present study examined the anatomically-specific regulation of progestin receptor (PR) expression by oestrogen receptor (ER) activation in the ventromedial nucleus (VMN) of the hypothalamus and the medial preoptic nucleus (MPN) of the neonatal female rat brain, using the selective oestrogen receptor modulators (SERMs), tamoxifen and ICI 182780 (ICI), in the presence or absence of oestradiol benzoate (EB) treatment. The results demonstrate that PR immunoreactivity (PR-ir) in the neonatal female MPN was significantly increased by EB and this increase was abolished by either tamoxifen or ICI treatment. In contrast, within the VMN of the same animals, EB had no effect on PR-ir and the SERMs only modestly decreased PR-ir. Interestingly, ICI acted as a true antagonist regardless of EB treatment, whereas tamoxifen acted as an ER agonist in the absence of EB in the MPN, but not the VMN, representing one of the first in vivo demonstrations of tissue-specific and oestradiol-independent effects of tamoxifen on ER activation. The present results indicate that PR expression is highly dependent on oestradiol and its receptor in the MPN, although it is independent of both oestradiol and ER activation within the neonatal VMN. These findings demonstrate the anatomically specific actions of oestradiol and its receptor to induce PR in two brain regions controlling different aspects of female reproductive behaviours in adulthood. PMID- 21981077 TI - Is rat an appropriate animal model to study the involvement of D-serine catabolism in schizophrenia? Insights from characterization of D-amino acid oxidase. AB - D-Amino acid oxidase (DAAO; EC1.4.3.3) has been proposed to play a main role in the degradation of D-serine, an allosteric activator of the N-methyl-D-aspartate type glutamate receptor in the human brain, and to be associated with the onset of schizophrenia. To prevent excessive D-serine degradation, novel drugs for schizophrenia treatment based on DAAO inhibition were designed and tested on rats. However, the properties of rat DAAO are unknown and various in vivo trials have demonstrated the effects of DAAO inhibitors on d-serine concentration in rats. In the present study, rat DAAO was efficiently expressed in Escherichia coli. The recombinant enzyme was purified as an active, 40 kDa monomeric flavoenzyme showing the basic properties of the dehydrogenase-oxidase class of flavoproteins. Rat DAAO differs significantly from the human counterpart because: (a) it possesses a different substrate specificity; (b) it shows a lower kinetic efficiency, mainly as a result of a low substrate affinity; (c) it differs in affinity for the binding of classical inhibitors; (d) it is a stable monomer in the absence of an active site ligand; and (e) it interacts with the mammalian protein modulator pLG72 yielding a ~100 kDa complex in addition to the ~200 kDa one, as formed by the human DAAO. Furthermore, the concentration of endogenous D serine in U87 glioblastoma cells was not affected by transfection with rat DAAO, whereas it was significantly decreased when expressing the human homologue. These results raise doubt on the use of the rat as a model system for testing new drugs against schizophrenia and indicate a different physiological function of DAAO in rodents and humans. PMID- 21981078 TI - Manipulation of host vesicular trafficking and innate immune defence by Legionella Dot/Icm effectors. AB - Legionella pneumophila, the causative agent of Legionnaires' disease, infects and replicates in macrophages and amoebas. Following internalization, L. pneumophila resides in a vacuole structure called Legionella-containing vacuole (LCV). The LCV escapes from the endocytic maturation process and avoids fusion with the lysosome, a hallmark of Legionella pathogenesis. Interference with the secretory vesicle transport and avoiding lysosomal targeting render the LCV permissive for L. pneumophila intracellular replication. Central to L. pneumophila pathogenesis is a defect in the organelle trafficking/intracellular multiplication (Dot/Icm) type IV secretion system that translocates a large number of effector proteins into host cells. Many of the Dot/Icm effectors employ diverse and sophisticated biochemical strategies to manipulate the host vesicular transport system, playing an important role in LCV biogenesis and trafficking. Similar to other bacterial pathogens, L. pneumophila also delivers effector proteins to modulate or counteract host innate immune defence pathways such as the NF-kappaB and apoptotic signalling. This review summarizes the known functions and mechanisms of Dot/Icm effectors that target host membrane trafficking and innate immune defence pathways. PMID- 21981079 TI - Anti-inflammatory activity of the oriental herb medicine, Arisaema cum Bile, in LPS-induced PMA-differentiated THP-1 cells. AB - Arisaema cum Bile is widely used as a folk medicine in Korea. However, the systematic biological properties of Arisaema cum Bile have seldom been addressed. In this study, we evaluated the anti-inflammatory activity of Arisaema cum Bile extract on lipopolysaccharide (LPS)-induced inflammation in phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophages. The Arisaema cum Bile extract markedly inhibited the production of pro-inflammatory cytokines including interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha, and also suppressed the mRNA and protein expressions of these cytokines. Furthermore, the Arisaema cum Bile extract also inhibited LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and gene expressions in PMA differentiaed THP-1 macrophages. These results suggest that Arisaema cum Bile extract may have potential for development into an effective anti-inflammatory agent, and/or as an ingredient of functional foods. PMID- 21981080 TI - All electrochemical fabrication of a platinized nanoporous Au thin-film catalyst. AB - In an effort to decrease the high cost associated with the design, testing, and production of electrocatalysts, a completely electrochemical scheme has been developed to deposit and platinize a nanoporous Au (NPG) based catalyst for formic acid oxidation. The proposed route enables synthesis of an alternative to the most established, nanoparticles based catalysts and addresses issues of the latter associated with either contamination inherent from the synthetic route or poor adhesion to the supporting electrode. The synthetic protocol includes as a first step, electrochemical codeposition of a Au((1-x))Ag(x) alloy in a thiosulfate based electrolyte followed by selective electrochemical dissolution (dealloying) of Ag as the less noble metal, that generates an ultrathin and preferably continuous porous structure featuring thickness of less than 20 nm. NPG is then functionalized with Pt (no thicker than 1 nm) by surface limited redox replacement (SLRR) of underpotentially deposited Pb layer to form Pt-NPG. SLRR ensures complete coverage of the surface with Pt, believed to spread evenly over the NPG matrix. Testing of the catalyst at a proof-of-concept level demonstrates its high catalytic activity toward formic acid oxidation. Current densities of 40-50 mA cm(-2) and mass activities of 1-3 A.mg(-1) (of combined Pt Au catalyst) have been observed and the Pt-NPG thin films have lasted over 2600 cycles in standard formic acid oxidation testing. PMID- 21981091 TI - Phenobarbital and some anesthesia implications. PMID- 21981092 TI - Neonatal revolution - the introduction of PEEP. AB - Fifty years ago, a baby born at 24-26 weeks was not considered viable. It was a tragedy for the mother having carried it for so long. I witnessed such an event as a student. The scourge of premature deliveries was the lack of surfactant in many tiny babies. In general, if a premature infant with hyaline membrane disease, as it was called respiratory distress syndrome (RDS), could not maintain a pO(2) above 60 mmHg in 100% oxygen, it was not expected to survive. In late 1969, two babies with suspected RDS came to ICU and were treated by the author with the buffer (tris hydroxyl amino methane, [THAM] which reduced both metabolic and respiratory acidosis and did not contain sodium) and an isoprenaline infusion (beta(1) stimulant and pulmonary vasodilator). The X-ray appearances of RDS disappeared. Unfortunately, one died of portal vein thrombosis because the drugs were administered by umbilical catheter, which were commonly used at the time. The other one recovered but the physicians then said the diagnosis must have been wrong! PMID- 21981093 TI - Caudal block in a child with a sacral dimple utilizing ultrasonography. PMID- 21981094 TI - Practical use of remifentanil for pediatric patients. PMID- 21981095 TI - Performance of GlideScope((r)) videolaryngoscope for nasotracheal intubation in children. PMID- 21981096 TI - Case report: sugammadex used to successfully reverse vecuronium-induced neuromuscular blockade in a 7-month-old infant. PMID- 21981097 TI - The transversus abdominis plane (TAP) block in neonates and infants - results of an audit. PMID- 21981098 TI - Use of ketamine in children - what are the next steps? PMID- 21981100 TI - Withdrawal treatment with clonidine after prolonged use of chloral hydrate in a pediatric intensive care patient. PMID- 21981101 TI - Valproate-induced hyperammonemia and seizures: perioperative concerns. PMID- 21981102 TI - Anesthesia for a child suffering from a deletion in the Xp21 loci resulting in Duchenne disease, glycerol kinase deficiency, and congenital adrenal hypoplasia. PMID- 21981103 TI - Paraplegia following caudal block in a child with Burkitt's lymphoma. PMID- 21981104 TI - Training and learning robotic surgery, time for a more structured approach: a systematic review. AB - BACKGROUND: Robotic assisted laparoscopic surgery is growing rapidly and there is an increasing need for a structured approach to train future robotic surgeons. OBJECTIVES: To review the literature on training and learning strategies for robotic assisted laparoscopic surgery. SEARCH STRATEGY: A systematic search of MEDLINE, EMBASE, the Cochrane Library and the Journal of Robotic Surgery was performed. SELECTION CRITERIA: We included articles concerning training, learning, education and teaching of robotic assisted laparoscopic surgery in any specialism. DATA COLLECTION AND ANALYSIS: Two authors independently selected articles to be included. We categorised the included articles into: training modalities, learning curve, training future surgeons, curriculum design and implementation. MAIN RESULTS: We included 114 full text articles. Training modalities such as didactic training, skills training (dry lab, virtual reality, animal or cadaver models), case observation, bedside assisting, proctoring and the mentoring console can be used for training in robotic assisted laparoscopic surgery. Several training programmes in general and specific programmes designed for residents, fellows and surgeons are described in the literature. We provide guidelines for development of a structured training programme. AUTHORS' CONCLUSIONS: Robotic surgical training consists of system training and procedural training. System training should be formally organised and should be competence based, instead of time based. Virtual reality training will play an import role in the near future. Procedural training should be organised in a stepwise approach with objective assessment of each step. This review aims to facilitate and improve the implementation of structured robotic surgical training programmes. PMID- 21981105 TI - Body mass index, sexual difficulties and sexual satisfaction among people in regular heterosexual relationships: a population-based study. AB - BACKGROUND/AIMS: The aims of this study were to clarify the relationship between body mass index (BMI) and sexual difficulties and to investigate if BMI influenced sexual satisfaction, over and above the effects of sexual difficulties. METHODS: Cross-sectional analyses of a nationally representative computer-assisted telephone interview. Eight thousand, six hundred and fifty-six respondents were recruited by random digit dialling in 2004-2005. Only those in a sexually active, heterosexual relationship were included in the current analyses. RESULTS: After adjustments for demographic factors, both overweight and obese male and female participants were more likely to report worrying during sex about whether their body was unattractive. Among women, associations were also found between higher BMI and lack of interest in sex. No other significant associations between BMI and sexual difficulties were evident. There was an association between BMI and extreme physical pleasure for women but not men over and above the effects of sexual difficulties, with obese women being more likely than normal weight women to report extreme physical pleasure. No associations were found for either men or women between BMI and whether or not they reported extreme emotional or sexual satisfaction with their relationship. CONCLUSIONS: With the exception of body image difficulties, there is little association between BMI and self-reported sexual difficulties. Furthermore, extreme sexual and emotional satisfaction appeared to be associated with the presence or absence of sexual difficulties and not overly influenced by BMI. Overall, clinicians and patients should be aware that being overweight is not necessarily detrimental to sexual functioning. PMID- 21981106 TI - Recurrent spontaneous hypoglycaemia causes loss of neurogenic and neuroglycopaenic signs in infants with congenital hyperinsulinism. AB - OBJECTIVE: Hypoglycaemia-associated autonomic failure (HAAF) with impaired neurogenic and neuroglycopaenic responses occurs in adults following recent, repeated hypoglycaemia. We aimed to evaluate whether HAAF also occurs in patients with infant-onset congenital hyperinsulinism (CHI). DESIGN, PATIENTS: A controlled fast was performed in (i) seven CHI infants with initial symptomatic hypoglycaemia and three recent episodes of spontaneous recurrent hypoglycaemia each lasting <5 min and in (ii) seven infants with idiopathic ketotic hypoglycaemia for control. MEASUREMENTS: At the time of hypoglycaemia (blood glucose <3 mmol/l or clinical signs), blood was drawn for serum insulin, cortisol, glucagon, adrenalin and nor-adrenalin. Signs of hypoglycaemia were documented. In CHI patients, the ABCC8 and KCNJ11 genes were analysed by denaturing high performance liquid chromatography (DHPLC) and/or direct bidirectional sequencing. RESULTS: Two CHI patients had a paternal ABCC8 mutation, five had no mutations. When repeated hypoglycaemia was provoked, all CHI patients exhibited a complete loss of clinical signs of hypoglycaemia, along with a global blunting of the counter-regulatory hormones cortisol, glucagon, growth hormone, adrenalin and nor-adrenalin responses (median values 256 nmol/l, 23 pmol/l, 5.6 mU/l, 390 pmol/l and 2.9 nmol/l, respectively), irrespective of mutational status. In the controls, hypoglycaemia was always clinically overt with normal counter-regulatory cortisol, glucagon, adrenalin and nor-adrenalin responses (530 nmol/l, 60, 920 pmol/l and 4.0 nmol/l, respectively). CONCLUSION: Recurrent hyperinsulinaemic hypoglycaemia even of short duration blunts the autonomic, neuroglycopaenic and glucose counter-regulatory hormonal responses in patients with infant-onset CHI resulting in clinically silent hypoglycaemia. Tight, or continuous, glucose monitoring is therefore recommended, especially in conservatively treated patients. PMID- 21981107 TI - New cyclopentenyl-linked [NPN] ligands and their coordination chemistry with zirconium: synthesis of a dinuclear side-on-bound dinitrogen complex. AB - The synthesis and characterization of two 1,2-cyclopentyl-bridged diiminophosphine proligands, (CY5)[NPN](DMP)H(2) (CY5 = cyclopentylidene; DMP = 2,6-Me(2)C(6)H(3)) and (CY5)[NPN](DIPP)H(2) (DIPP = 2,6-(i)Pr(2)C(6)H(3)), are presented, and tautomerization to the corresponding 1,2-cyclopentenyl-bridged enamineimine phosphine precursors is reported. These two new proligands are obtained by deprotonation of N-DMP- or N-DIPP-cyclopentylideneimine (N-DMP, 2,6 dimethylphenyl; N-DIPP, 2,6-diisopropylphenyl) and the subsequent addition of 0.5 equiv of dichlorophenylphosphine. Each ligand precursor exists as a mixture of isomers that consist of the diimine, enamineimine, and dienamine tautomers and corresponding stereoisomers, each of which could be identified. The bis(dimethylamido)zirconium complexes (CY5)[NPN](DMP)Zr(NMe(2))(2) and (CY5)[NPN](DIPP)Zr(NMe(2))(2) were prepared directly from the neutral proligands and Zr(NMe(2))(4) via protonolysis. Exchange of the dimethylamido ligands in the latter complexes for chlorides and iodides takes place upon reaction with excess Me(3)SiCl and Me(3)SiI, respectively. A dinuclear zirconium-dinitrogen complex, {(CY5)[NPN](DMP)Zr(THF)}(2)(MU-eta(2):eta(2)-N(2)), was obtained via KC(8) reduction of (CY5)[NPN](DMP)ZrCl(2) under 4 atm of N(2). On the basis of single crystal X-ray analysis, N(2) has been reduced to a side-on-bound hydrazido (MU eta(2):eta(2)-N(2)(4-)) unit. This dinitrogen complex is thermally unstable and decomposes in solution. PMID- 21981108 TI - JC virus granular neuronopathy and rhombencephalic progressive multifocal leukoencephalopathy: case report and review of the literature. AB - JC virus (JCV) granular neuronopathy remains an under-appreciated phenomenon whereby JCV inhabits neurons in the granular layer of the cerebellum causing neuronal loss, gliosis and a clinical cerebellar syndrome. The following case describes a man with sarcoidosis and idiopathic leukopenia who developed a clinical cerebellar syndrome due to JCV granular neuronopathy, followed by neurological decline due to rhombencephalic progressive multifocal leukoencephalopathy. This case reminds us of the ability of JCV to produce dual neuropathology which includes JCV granular neuronopathy, and the pathogenesis and clinical implications for this phenomenon are discussed. PMID- 21981109 TI - Human immunodeficiency virus prevalence, incidence, and residual risk of transmission by transfusions at Retrovirus Epidemiology Donor Study-II blood centers in Brazil. AB - BACKGROUND: In Brazil nationally representative donor data are limited on human immunodeficiency virus (HIV) prevalence, incidence, and residual transfusion risk. The objective of this study was to analyze HIV data obtained over 24 months by the Retrovirus Epidemiology Donor Study-II program in Brazil. STUDY DESIGN AND METHODS: Donations reactive to third- and fourth-generation immunoassays (IAs) were further confirmed by a less-sensitive (LS) IA algorithm and Western blot (WB). Incidence was calculated for first-time (FT) donors using the LS-EIA results and for repeat donors with a model developed to include all donors with a previous negative donation. Residual risk was projected by multiplying composite FT and repeat donor incidence rates by HIV marker-negative infectious window periods. RESULTS: HIV prevalence among FT donors was 92.2/10(5) donations. FT and repeat donor and composite incidences were 38.5 (95% confidence interval [CI], 25.6-51.4), 22.5 (95% CI, 17.6-28.0), and 27.5 (95% CI, 22.0-33.0) per 100,000 person-years, respectively. Male and community donors had higher prevalence and incidence rates than female and replacement donors. The estimated residual risk of HIV transfusion transmission was 11.3 per 10(6) donations (95% CI, 8.4-14.2), which could be reduced to 4.2 per 10(6) donations (95% CI, 3.2 5.2) by use of individual-donation nucleic acid testing (NAT). CONCLUSION: The incidence and residual transfusion risk of HIV infection are relatively high in Brazil. Implementation of NAT will not be sufficient to decrease transmission rates to levels seen in the United States or Europe; therefore, other measures focused on decreasing donations by at-risk individuals are also necessary. PMID- 21981110 TI - An unusual case of congenitally corrected transposition of the great arteries associated with noncompaction-like remodeling of the morphological right ventricle. AB - Congenitally corrected transposition of the great arteries is a rare disease characterized by atrio-ventricular and ventriculo-arterial discordance (double discordance) and is associated with other cardiac anomalies in the majority of cases. The important associated anomalies include ventricular septal defect, abnormalities of left atrioventricular valve, subpulmonary stenosis, and conduction abnormalities. However, the noncompaction-like remodeling of the subaortic, morphologic right ventricle is not a commonly reported association. We, report a case of congenitally corrected transposition of the great arteries in a 40-year-old male patient, who had noncompaction-like remodeling of the morphologic right ventricle with severe ventricular dysfunction. He also had, left-sided Ebstein's anomaly, severe left atrioventricular valve regurgitation and a 2:1 atrioventricular conduction block. PMID- 21981111 TI - Elucidating the roles of ethanol fermentation metabolism in causing off-flavors in mandarins. AB - To elucidate the roles of ethanol fermentation metabolism in causing off-flavors, 'Mor' mandarins were exposed to anaerobic atmospheres for 0, 2, 4, 7, and 10 days to gradually increase juice ethanol and acetaldehyde levels through enhanced fermentation. Exposure to anaerobic atmosphere caused progressive decline in fruit sensory quality, from nearly "good" to "very bad", because of decreased typical mandarin flavor and increased sensation of 'musty' and 'ethanol' off flavors. GC-MS analysis revealed significant (p <= 0.05) increases in the contents of 12 aroma volatiles, including the ethanol fermentation metabolites ethanol and acetaldehyde, and several fatty acid and amino acid catabolism derivates, 7 of which were ethyl esters, which suggests that they were esterification products of ethanol and acyl-CoA's derived from fatty acid and amino acid catabolism. These de novo synthesized anaerobiosis-regulated ethyl esters impart 'pungent', 'ethereal', 'waxy', 'musty', and 'fruity' notes. Overall, these results suggest that besides the direct effects of ethanol and acetaldehyde, downstream ethanol esterification products may also be involved in causing off-flavor sensation in mandarins. PMID- 21981112 TI - Andean uplift promotes lowland speciation through vicariance and dispersal in Dendrocincla woodcreepers. AB - Andean uplift contributed importantly to the build-up of high Neotropical diversity. Final uplift of the Eastern Cordillera of Colombia separated once contiguous lowland faunas east and west of the Andes between 5 and 3.5 million years ago (Ma hereafter). We used DNA sequences from several moderate- to fast evolving mitochondrial and two slow-evolving nuclear genes to generate a well supported phylogeny of Dendrocincla woodcreepers, a genus with multiple species endemic to lowland regions both east and west of the Andes. A time-calibrated phylogeny and dispersal-vicariance analysis indicated that uplift of the Eastern Cordillera of Colombia resulted in the initial vicariant separation of a widespread lowland form east and west of the Andes at c. 3.6 Ma. This was followed by two separate east-to-west dispersal events over or around the completed Andes, each producing a genetically distinct lineage. Our analysis suggests that Andean uplift promoted the build-up of biodiversity in lowland Neotropical faunas both through vicariance-based speciation during uplift and through dispersal-based speciation following uplift. In contrast to the multiple colonizations of the trans-Andean region by Dendrocincla, the Atlantic Forest was colonized from the Amazon only once, followed by in situ diversification. PMID- 21981113 TI - Older adults' experiences regarding discharge from hospital following orthopaedic intervention: a metasynthesis. AB - PURPOSE: To identify and synthesise qualitative literature on the older adults' perspectives of being discharged from hospital following orthopaedic intervention. METHODS: A systematic search of nine databases, for qualitative research published between 1950 and December 2010, exploring the lived experience of older adults being discharged from hospital following orthopaedic surgery was undertaken. Included papers were evaluated using the Critical Appraisal Skills Programme (CASP) quality guidelines. Data were extracted and themes synthesised, using an EXCEL spreadsheet to assist with organisation of data. RESULTS: From the 16 papers included in the review, four themes were identified: 1) mental outlook; 2) loss of independence; 3) function and activity limitations; and 4) coping with pain. Mental outlook was central to the other three themes. CONCLUSIONS: Older adults' experiences around hospital discharge, collected through qualitative research, provide health authorities with valuable information that could be used in care pathway planning. Health professionals involved in in-patient and community care should be aware that a perceived loss of independence, function and activity limitations, and the ability to cope with pain can influence mental outlook and consequently rehabilitation. PMID- 21981114 TI - Maternal care received by individual pups correlates with adult CA1 dendritic morphology and synaptic plasticity in a sex-dependent manner. AB - Maternal care is an important environmental factor for rats early in life. Adult offspring from dams exhibiting extremely high versus low maternal care differ remarkably in dendritic complexity and long-term synaptic potentiation in the CA1 area. However, >70% of the pups do not belong to these extreme categories of maternal care, questioning the general relevance of these observations. Therefore, the present study investigated whether the influence of maternal care is discernable over its entire range and can serve as an index predicting later CA1 structure and function. The amount of licking and grooming (%LG) received was determined for each pup during the first postnatal week. In males, both total apical branch length and dendritic complexity correlated significantly and positively with %LG. In females, we observed a nonsignificant negative correlation, also when controlled for variations in oestradiol and progesterone levels. The correlation in females was significantly different from that in males. No significant correlation was observed between the %LG and the amount of synaptic potentiation, either in male or in female offspring, regardless of whether slices had been treated with corticosterone or vehicle. However, in male rats, the degree of potentiation seen after corticosterone compared to vehicle treatment was almost significantly related to the %LG received early in life; this differed significantly from that observed in females. The data from the present study suggest that %LG received early in life results in mild, yet sex dependent effects on adult CA1 structure and function. PMID- 21981115 TI - Soft interactions at nanoparticles alter protein function and conformation in a size dependent manner. AB - Weak protein-nanoparticle (NP) interactions are studied in a low binding regime as a model for the soft protein corona around nanoparticles in complex biological fluids. Noncovalent, reversible interactions between Subtilisin Carlsberg (SC) and silica NPs shows significant alteration in conformation and enzymatic activity in a NP-size dependent manner. Very weak interactions between SC and silica NPs were revealed by centrifugation-based separations and further supported by small-angle X-ray scattering, while bovine serum albumin was used as a strongly interacting reference. Secondary and tertiary structure changes of SC were studied via circular dichroism and correlated to enzymatic activity where the enzyme kinetics showed a critical role for nanoparticle size. PMID- 21981116 TI - Biofilm formation by the yeast Rhodotorula mucilaginosa: process, repeatability and cell attachment in a continuous biofilm reactor. AB - Yeast biofilms contribute to quality impairment of industrial processes and also play an important role in clinical infections. Little is known about biofilm formation and their treatment. The aim of this study was to establish a multi layer yeast biofilm model using a modified 3.7 l bench-top bioreactor operated in continuous mode (D = 0.12 h(-1)). The repeatability of biofilm formation was tested by comparing five bioprocesses with Rhodotorula mucilaginosa, a strain isolated from washing machines. The amount of biofilm formed after 6 days post inoculation was 83 MUg cm(-2) protein, 197 MUg cm(-2) polysaccharide and 6.9 * 10(6) CFU cm(-2) on smooth polypropylene surfaces. Roughening the surface doubled the amount of biofilm but also increased its spatial variability. Plasma modification of polypropylene significantly reduced the hydrophobicity but did not enhance cell attachment. The biofilm formed on polypropylene coupons could be used for sanitation studies. PMID- 21981117 TI - Anti-inflammatory, antinociceptive and anti-angiogenic activities of a phospholipid mixture purified from porcine lung tissues. AB - This work aimed to assess anti-inflammatory and related properties of a phospholipid mixture purified from porcine lung tissues, named KT&G101, which is being developed as a novel topical remedy for atopic dermatitis. KT&G101 consists of pure phospholipids, mainly phosphatidylcholine (PC) and other phospholipids such as phosphatidylinositol (PI) and phosphatidylserine (PS). Its predominant PC species is 1,2-dipalmitoylphosphatidylcholine (DPPC). KT&G101 exhibited an anti angiogenic activity in the chick chorioallantoic membrane (CAM) assay. Oral administration of KT&G101 at the dosages of 100, 200 and 400 mg/kg body weight gave rise to an inhibition of 15.4%, 25.3% and 30.1% in the vascular permeability assay, respectively. In the carrageenan-induced inflammation in the air pouches, KT&G101 significantly diminished the volume of exudates in the pouches, the number of polymorphonuclear leukocytes and nitrite content in exudates. In the acetic acid-induced writhing response, oral administration of KT&G101 at the dosages of 50, 100 and 200 mg/kg body weight showed the reduction of 21.6%, 51.6% and 60.8% in the pain response of mice, respectively. It was also able to diminish the nitric oxide (NO) and reactive oxygen species (ROS) levels in the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. KT&G101 displayed a significant suppression on the induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the stimulated RAW264.7 cells. However, the free radical scavenging activity of KT&G101 was detected to be very weak in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Taken together, KT&G101 possesses anti-inflammatory and related antinociceptive and anti-angiogenic activities, which indirectly supports its use as an anti-atopic therapy. PMID- 21981118 TI - Novel p.M96T variant of NRL and shRNA-based suppression and replacement of NRL mutants associated with autosomal dominant retinitis pigmentosa. AB - Mutations in the gene encoding the transcription factor neural retina leucine zipper (NRL) are known to cause autosomal dominant (adRP) or recessive (arRP) retinitis pigmentosa (RP). In an adRP Spanish family, we detected a novel sequence variation (c.287T>C) in the NRL gene that results in the p.M96T protein change. A functional test of the ability of NRL, in conjunction with cone-rod homeobox (CRX), to transactivate a human rhodopsin (RHO) promoter was used to evaluate the pathogenic mechanisms of NRL. We found upregulation of the RHO promoter by p.M96T protein similar to that shown by other missense NRL mutations that cause adRP. Affected RP patients of the family carry the nucleotide change, although two other family members that also carry the c.287T>C variation remain asymptomatic. This result complicates the genetic counselling of the family. The pathogenic mechanisms associated with adRP NRL mutations appear to be caused by a gain of function. To suppress the negative effect of an NRL mutant, the suppression and replacement strategy seems to be the most suitable therapeutic approach capable of overcoming the mutational heterogeneity associated with NRL linked adRP. Thus, we evaluated this methodology in the NRL gene for the first time. PMID- 21981119 TI - Analysis of the BadA stalk from Bartonella henselae reveals domain-specific and domain-overlapping functions in the host cell infection process. AB - Human pathogenic Bartonella henselae cause cat scratch disease and vasculoproliferative disorders. An important pathogenicity factor of B. henselae is the trimeric autotransporter adhesin Bartonella adhesin A (BadA) which is modularly constructed and consists of a head, a long and repetitive neck-stalk module with 22 repetitive neck/stalk repeats and a membrane anchor. The BadA head is crucial for bacterial adherence to host cells, binding to several extracellular matrix proteins and for the induction of vascular endothelial growth factor (VEGF) secretion. Here, we analysed the biological role of the BadA stalk in the infection process in greater detail. For this purpose, BadA head bearing and headless deletion mutants with different lengths (containing one or four neck/stalk repeats in the neck-stalk module) were produced and functionally analysed for their ability to bind to fibronectin, collagen and endothelial cells and to induce VEGF secretion. Whereas a head-bearing short version (one neck/stalk element) of BadA lacks exclusively fibronectin binding, a substantially truncated headless BadA mutant was deficient for all of these biological functions. The expression of a longer headless BadA mutant (four neck/stalk repeats) restored fibronectin and collagen binding, adherence to host cells and the induction of VEGF secretion. Our data suggest that (i) the stalk of BadA is exclusively responsible for fibronectin binding and that (ii) both the head and stalk of BadA mediate adherence to collagen and host cells and the induction of VEGF secretion. This indicates overlapping functions of the BadA head and stalk. PMID- 21981120 TI - Biodegradable nanoparticles meet the bronchial airway barrier: how surface properties affect their interaction with mucus and epithelial cells. AB - Despite the wide interest raised by lung administration of nanoparticles (NPs) for the treatment of various diseases, little information is available on their effect toward the airway epithelial barrier function. In this study, the potential damage of the pulmonary epithelium upon exposure to poly(lactide-co glycolide) (PLGA) NPs has been assessed in vitro using a Calu-3-based model of the bronchial epithelial barrier. Positively and negatively charged as well as neutral PLGA NPs were obtained by coating their surface with chitosan (CS), poloxamer (PF68), or poly(vinyl alcohol) (PVA). The role of NP surface chemistry and charge on the epithelial resistance and mucus turnover, using MUC5AC as a marker, was investigated. The interaction with mucin reduced the penetration of CS- and PVA-coated NPs, while the hydrophilic PF68-coated NPs diffused across the mucus barrier leading to a higher intracellular accumulation. Only CS-coated NPs caused a transient but reversible decrease of the trans-epithelial electrical resistance (TEER). None of the NP formulations increased MUC5AC mRNA expression or the protein levels. These in vitro results highlight the safety of PLGA NPs toward the integrity and function of the bronchial airway barrier and demonstrate the crucial role of NP surface properties to achieve a controlled and sustained delivery of drugs via the pulmonary route. PMID- 21981121 TI - Thermodynamics, kinetics, and photochemistry of beta-strand association and dissociation in a split-GFP system. AB - Truncated green fluorescent protein (GFP) that is refolded after removing the 10th beta-strand can readily bind to a synthetic strand to recover the absorbance and fluorescence of the whole protein. This allows rigorous experimental determination of thermodynamic and kinetic parameters of the split system including the equilibrium constant and the association/dissociation rates, which enables residue-specific analysis of peptide-protein interactions. The dissociation rate of the noncovalently bound strand is observed by strand exchange that is accompanied by a color change, and surprisingly, the rate is greatly enhanced by light irradiation. This peptide-protein photodissociation is a very unusual phenomenon and can potentially be useful for introducing spatially and temporally well-defined perturbations to biological systems as a genetically encoded caged protein. PMID- 21981134 TI - Multidetector row helical computed tomography for invasive ductal carcinoma of the breast: correlation between radiological findings and the corresponding biological characteristics of patients. AB - The aim of this study is to evaluate the correlation between multidetector row helical computed tomography (MDCT) findings and the histopathological characteristics of patients with invasive ductal carcinoma. We retrospectively reviewed MDCT findings and the corresponding histopathological features of 442 women with invasive ductal carcinoma. We received informed consent from the patients and the protocol was approved by the Ethics Committee at Tohoku University. The median age was 53 years (26-89 years). We examined the MDCT findings based on mass shape classified into well, moderate, poorly and scattered demarcated shapes, the enhancement pattern classified into homogenous, heterogeneous, rim and poor, and mass density classified into high, intermediate or low. We subsequently compared these radiological findings with the histological characteristics and clinical outcome. Poorly demarcated types were higher in ER+/HER2- (P = 0.008), while the well-demarcated type was higher in ER /HER2- and ER-/HER2+ (P < 0.001 and P = 0.010). Rim pattern was higher in ER /HER2- (P < 0.001). Intermediate or low density was higher in ER-/HER2- (P < 0.001, respectively). Further analysis based on histological grade, mitotic counts and lymphovascular invasion demonstrated that the well-demarcated shape was higher in grade 2 and 3 (P = 0.006 and P < 0.001, respectively), and rim pattern was observed in grade 3 (P < 0.001). Regarding mitotic counts, poorly and scattered demarcated shapes were observed in score 1 (P = 0.008 and P = 0.014), while well-demarcated shape and rim enhancement were observed in score 3 (P < 0.001, respectively). Lymphovascular invasion correlated with a moderate demarcated shape (P = 0.029). Regarding recurrence rates, there were statistically significant differences between well and moderate, poorly or scattered demarcated shapes (P = 0.007, 0.028 and 0.035, respectively). These proposed MDCT diagnostic criteria based on biological characteristics contribute to more accurately predicting the biological behavior of breast cancer patients. PMID- 21981135 TI - Indigenous beliefs about biomedical and bush medicine treatment efficacy for indigenous cancer patients: a review of the literature. AB - BACKGROUND: Australia's indigenous people suffer from higher cancer mortality than non-indigenous Australians, a discrepancy partly caused by differences in beliefs about treatment efficacy between Indigenous patients and their non indigenous healthcare providers. This paper critically reviews the literature associated with Indigenous beliefs about cancer treatment, both 'bush medicine' and biomedical, in order to provide recommendations to healthcare providers about accommodating indigenous beliefs when treating cancer. METHODS: A search was undertaken of peer-reviewed journal papers using electronic databases and citation snowballing. Papers were selected for inclusion based upon relevance to themes that addressed the research questions. RESULTS: Literature suggests that indigenous beliefs about treatment efficacy for cancer involve five themes: (i) concerns about the toxicity of treatment; (ii) disconnect with the physician; (iii) fears about absence from home during treatment; (iv) different beliefs about disease aetiology; (v) biomedical cancer treatments failing to address holistic health. CONCLUSIONS: Although some information is known about indigenous Australian healing beliefs and practices associated with cancer treatment, few studies have addressed ways in which indigenous and biomedical approaches to cancer treatment might be integrated. Some recent work has examined the role of belief in cancer treatment, specifically bush medicine, but more research is required. PMID- 21981136 TI - Interaction of carbene and olefin donors with [Cl2PN]3: exploration of a reductive pathway toward (PN)3. AB - The iminophosphine-phosphazene [P(III)-P(V)] heterocyclic adduct [IPr.PN(PCl(2)N)(2)] was prepared via reduction of the cyclic phosphazene [Cl(2)PN](3) in the presence of the carbene donor IPr {IPr = [(HCNDipp)(2)C:], where Dipp = 2,6-(i)Pr(2)C(6)H(3)}. By contrast, the treatment of [Cl(2)PN](3) with the N-heterocyclic olefin IPr?CH(2) yielded the olefin-grafted phosphazene ring [(IPr?CH)P(Cl)N(PCl(2)N)(2)]. PMID- 21981137 TI - Multifaceted link between cancer and inflammation. AB - Increasing evidence from epidemiological, preclinical and clinical studies suggests that dysregulated inflammatory response plays a pivotal role in a multitude of chronic ailments including cancer. The molecular mechanism(s) by which chronic inflammation drives cancer initiation and promotion include increased production of pro-inflammatory mediators, such as cytokines, chemokines, reactive oxygen intermediates, increased expression of oncogenes, COX 2 (cyclo-oxygenase-2), 5-LOX (5-lipoxygenase) and MMPs (matrix metalloproteinases), and pro-inflammatory transcription factors such as NF-kappaB (nuclear factor kappaB), STAT3 (signal transducer and activator of transcription 3), AP-1 (activator protein 1) and HIF-1alpha (hypoxia-inducible factor 1alpha) that mediate tumour cell proliferation, transformation, metastasis, survival, invasion, angiogenesis, chemoresistance and radioresistance. These inflammation associated molecules are activated by a number of environmental and lifestyle related factors including infectious agents, tobacco, stress, diet, obesity and alcohol, which together are thought to drive as much as 90% of all cancers. The present review will focus primarily on the role of various inflammatory intermediates responsible for tumour initiation and progression, and discuss in detail the critical link between inflammation and cancer. PMID- 21981140 TI - One country, two worlds - the health disparity in China. AB - As result of its spectacular economic growth, millions of Chinese have been lifted out of poverty, making China a model for impoverished countries. Although, for many, economic growth has led to prosperity, ever-growing disparities exist between those who have benefited from the economic advancement and those left behind. Massive gaps in development exist between: regions, urban and rural and social groups. This contribution is to develop a detailed understanding of the health disparity in China by examining the discrepancies in major health indicators. Current efforts to reduce the disparities, and its challenges, opportunities and global implications are also assessed. PMID- 21981138 TI - Rabs and EHDs: alternate modes for traffic control. AB - Endocytic trafficking is a highly organized process regulated by a network of proteins, including the Rab family of small GTP-binding proteins and the C terminal EHDs (Eps15 homology-domain-containing proteins). Central roles for Rab proteins have been described in vesicle budding, delivery, tethering and fusion, whereas little is known about the functions of EHDs in membrane transport. Common effectors for these two protein families have been identified, and they facilitate regulation of sequential steps in transport. By comparing and contrasting key aspects in their modes of function, we shall promote a better understanding of how Rab proteins and EHDs regulate endocytic trafficking. PMID- 21981139 TI - Targeted inhibition of BRAF kinase: opportunities and challenges for therapeutics in melanoma. AB - Malignant melanoma is the most aggressive form of skin cancer and its incidence has increased dramatically in the last two decades. Even with a high rate of success in the treatment of early stages of this malignancy, currently there are no effective strategies for the treatment of advanced metastatic melanoma. Much effort has been put into the use of different target-specific drugs, among which BRAF kinase-specific small-molecule inhibitors have rendered promising results as therapeutic agents in metastatic melanoma. Nonetheless, some side effects, such as development of SCC (squamous cell carcinoma), as well as tumour resistance and recurrence, are common limitations of this therapeutic strategy. The use of combination treatments in which different regulatory pathways or the immunological response are targeted seems to be a promising tool for the future success of melanoma therapeutics. PMID- 21981141 TI - Impact of ageing on biological features of bone marrow stromal cells (BMSC) in cell transplantation therapy for CNS disorders: functional enhancement by granulocyte-colony stimulating factor (G-CSF). AB - This study was designed to clarify the effects of donor age on biological features of bone marrow stromal cells (BMSC), one of the candidates for cell transplantation therapy for CNS disorders, because many aged patients might require such therapy. This study was also aimed to test whether ex vivo treatments with granulocyte-colony stimulating factor (G-CSF) could modify biological properties of BMSC from aged donors and enhance its therapeutic effects in an animal model of traumatic brain injury. The BMSC were harvested from young (6-week-old) and aged (100-week-old) rats. The ageing significantly increased the senescence-associated beta-galactosidase (SA-beta-gal) activity of the cultured BMSC, and decreased their proliferative capacity and production of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). As the next step, the rats were subjected to brain freezing injury by applying liquid nitrogen onto the neocortex through the thinned skull. The 6-week BMSC, 100-week BMSC, G-CSF-treated 100-week BMSC or vehicle were stereotactically injected into the ipsilateral striatum at 7 days post-injury. Transplantation of the 6-week BMSC, but not 100-week BMSC, significantly improved locomotor function. However, treatment of the 100-week BMSC with 0.1 umol of G-CSF significantly improved their proliferation activity and growth factor production, and recovered therapeutic effects in the injured brain. In conclusion, donor age may largely determine biological aspects of BMSC. G-CSF may contribute to improve the outcome of BMSC transplantation therapy for CNS disorders in aged patients. PMID- 21981142 TI - The natural history of the normal/mild elevated TSH serum levels in children and adolescents with Hashimoto's thyroiditis and isolated hyperthyrotropinaemia: a 3 year follow-up. AB - OBJECTIVE: The natural history of Hashimoto's thyroiditis (HT) and isolated hyperthyrotropinaemia (IH) is not well defined. We therefore studied the natural course of patients with HT and IH and looked for possible prognostic factors. DESIGN: This is retrospective cross-sectional study. PATIENTS: Three hundred and twenty-three patients with HT (88 boys and 235 girls) and 59 with IH (30 boys and 29 girls), mean age 9.9 +/- 3.8 years were included in the study. When first examined, 236 of the children with HT had a normal TSH (G0) and in 87, it was elevated but <100% of the upper limit (G1). All IH subjects had elevated TSH. Potential risk factors for thyroid failure were evaluated after 3 years and included the presence or familiarity for endocrine/autoimmune diseases, premature birth, signs and symptoms of hypothyroidism, TSH levels, antithyroid antibodies and thyroid volume. RESULTS: HT: Of those with HT, 170 G0 patients remained stable, 31 moved to G1 and 35 to G2 (hypothyroidism). Thirty-six G1 children moved to G0, 17 remained stable and 34 moved to G2. Of patients with IH: 23 normalized, 28 remained stable and eight became overtly hypothyroid. In patients with HT, the presence of coeliac disease, elevated TSH and thyroid peroxidase antibodies (TPOAb) increased the risk of developing hypothyroidism by 4.0-, 3.4- and 3.5-fold, respectively. The increase in TSH levels during follow-up was strongly predictive of the development of hypothyroidism. In patients with IH, no predictive factor could be identified. CONCLUSIONS: Coeliac disease, elevated TSH and TPOAb at presentation and a progressive increase in TSH are predictive factors for thyroid failure in HT patients. PMID- 21981143 TI - Cellular strategies for making monoubiquitin signals. AB - Post-translational modification of proteins with ubiquitin regulates a variety of eukaryotic cellular processes. Ubiquitin can be conjugated to substrates either as a single moiety (monoubiquitination) or as isopeptide bond-linked chains (polyubiquitination), creating an array of ubiquitin signals. It has been established that monoubiquitination can serve important functions in many biological processes such as the regulation of gene transcription, protein trafficking, and DNA repair. Surprisingly, little is known about the mechanisms by which monoubiquitin signals are produced in the cell. Here, we discuss the potential cellular strategies for generating monoubiquitinated proteins using a few, relatively well characterized examples of monoubiquitinated proteins. These strategies include coupling ubiquitination to low affinity ubiquitin binding, using monoubiquitination-dedicated E2 conjugating enzymes, and restricting ubiquitin chain elongation. Some of these principles may be applicable to protein modifications involving ubiquitin like proteins (UBLs), which often occur in monomeric form. PMID- 21981144 TI - Comparative population genetic structure in a plant-pollinator/seed predator system. AB - Comparative analyses of spatial genetic structure of populations of plants and the insects they interact with provide an indication of how gene flow, natural selection and genetic drift may jointly influence the distribution of genetic variation and potential for local co-adaptation for interacting species. Here, we analysed the spatial scale of genetic structure within and among nine populations of an interacting species pair, the white campion Silene latifolia and the moth Hadena bicruris, along a latitudinal gradient across Northern/Central Europe. This dioecious, short-lived perennial plant inhabits patchy, often disturbed environments. The moth H. bicruris acts both as its pollinator and specialist seed predator that reproduces by laying eggs in S. latifolia flowers. We used nine microsatellite markers for S. latifolia and eight newly developed markers for H. bicruris. We found high levels of inbreeding in most populations of both plant and pollinator/seed predator. Among populations, significant genetic structure was observed for S. latifolia but not for its pollinator/seed predator, suggesting that despite migration among populations of H. bicruris, pollen is not, or only rarely, carried over between populations, thus maintaining genetic structure among plant populations. There was a weak positive correlation between genetic distances of S. latifolia and H. bicruris. These results indicate that while significant structure of S. latifolia populations creates the potential for differentiation at traits relevant for the interaction with the pollinator/seed predator, substantial gene flow in H. bicruris may counteract this process in at least some populations. PMID- 21981146 TI - Mapping the density of scattering centers limiting the electron mean free path in graphene. AB - Recently, giant carrier mobility MU (>10(5) cm(2) V(-1) s(-1)) and micrometer electron mean free path (l) have been measured in suspended graphene or in graphene encapsulated between inert and ultraflat BN layers. Much lower MU values (10000-20000 cm(2) V(-1) s(-1)) are typically reported in graphene on common substrates (SiO(2), SiC) used for device fabrication. The debate on the factors limiting graphene electron mean free path is still open with charged impurities (CI) and resonant scatterers (RS) indicated as the most probable candidates. As a matter of fact, the inhomogeneous distribution of such scattering sources in graphene is responsible of nanoscale lateral inhomogeneities in the electronic properties, which could affect the behavior of graphene nanodevices. Hence, high resolution two-dimensional (2D) mapping of their density is very important. Here, we used scanning capacitance microscopy/spectroscopy to obtain 2D maps of l in graphene on substrates with different dielectric permittivities, that is, SiO(2) (kappa(SiO2) = 3.9), 4H-SiC (0001) (kappa(SiC) = 9.7) and the very-high-kappa perovskite strontium titanate, SrTiO(3) (001), briefly STO (kappa(STO) = 330). After measuring l versus the gate bias V(g) on an array of points on graphene, maps of the CI density (N(CI)) have been determined by the neutrality point shift from V(g) = 0 V in each curve, whereas maps of the RS density (N(RS)) have been extracted by fitting the dependence of l on the carrier density (n). Laterally inhomogeneous densities of CI and RS have been found. The RS distribution exhibits an average value ~3 * 10(10) cm(-2) independently on the substrate. For the first time, a clear correlation between the minima in the l map and the maxima in the N(CI) map is obtained for graphene on SiO(2) and 4H-SiC, indicating that CI are the main source of the lateral inhomogeneity of l. On the contrary, the l and N(CI) maps are uncorrelated in graphene on STO, while a clear correlation is found between l and N(RS) maps. This demonstrates a very efficient dielectric screening of CI in graphene on STO and the role of RS as limiting factor for electron mean free path. PMID- 21981240 TI - Male reproductive success increases with alliance size in Indo-Pacific bottlenose dolphins (Tursiops aduncus). AB - 1. Determining the extent of variation in male mating strategies and reproductive success is necessary to understand the fitness benefits of social and cooperative behaviour. 2. This study assesses the reproductive success of male Indo-Pacific bottlenose dolphins in a small embayment population where different behavioural strategies of males have previously been identified. Parentage for 44 sampled calves was examined using 23 microsatellite loci and one mitochondrial DNA marker. Our candidate parent pool of 70 males and 64 females contained individuals sampled from both the embayment and adjacent coastal populations. 3. A moderate level of polygyny was detected in our sample. We assigned paternity of 23 calves to 12 males at the strict 95% confidence level and an additional nine calves to two males at the 80% confidence level. The majority (92%) of successful males were identified as residents to the embayment, and 46% of offspring were located within the same social group or community as their father. 4. Our results suggest that the size of alliances was the best predictor of reproductive success for males in this population, while the strength of association among allied males, alliance stability and male ranging patterns had little influence. In line with predictions for male alliances formed between unrelated individuals, we found that reproductive skew within alliances was not large. 5. Together, our genetic and behavioural analyses demonstrate that alliance formation between male dolphins is a successful strategy to enhance reproductive output. PMID- 21981242 TI - Diagnostic value of the allergen, Pru p 1 in adult patients with birch pollen associated oral allergy syndrome. PMID- 21981145 TI - Up-regulation of neurosteroid biosynthesis as a pharmacological strategy to improve behavioural deficits in a putative mouse model of post-traumatic stress disorder. AB - Benzodiazepines remain the most frequently used psychotropic drugs for the treatment of anxiety spectrum disorders; however, their use is associated with the development of tolerance and dependence. Another major hindrance is represented by their lack of efficacy in many patients, including patients with post-traumatic stress disorder (PTSD). For these nonresponders, the use of selective serotonin reuptake inhibitors (SSRIs) has been the therapy of choice. In the past decade, clinical studies have suggested that the pharmacological action of SSRIs may include the ability of these drugs to normalise decreased brain levels of neurosteroids in patients with depression and PTSD; in particular, the progesterone derivative allopregnanolone, which potently, positively and allosterically modulates the action of GABA at GABA(A) receptors. Preclinical studies using the socially-isolated mouse as an animal model of PTSD have demonstrated that fluoxetine and congeners ameliorate anxiety-like behaviour, fear responses and aggressive behaviour expressed by such mice by increasing corticolimbic levels of allopregnanolone. This is a novel and more selective mechanism than serotonin reuptake inhibition, which, for half a century, has been considered to be the main molecular mechanism for the therapeutic action of SSRIs. Importantly, this finding may shed light on the high rates of SSRI resistance among patients with PTSD and depression, comprising disorders in which there appears to be a block in allopregnanolone synthesis. There are several different mechanisms by which such a block may occur, and SSRIs may only be corrective under some conditions. Thus, the up-regulation of allopregnanolone biosynthesis in corticolimbic neurones may offer a novel nontraditional pharmacological target for a new generation of potent nonsedating, anxiolytic medications for the treatment of anxiety, depression, and PTSD: selective brain steroidogenic stimulants. PMID- 21981241 TI - Alloimmunization to transfused platelets requires priming of CD4+ T cells in the splenic microenvironment in a murine model. AB - BACKGROUND: Alloantibodies are a clinically significant sequelae of platelet (PLT) transfusion, potentially rendering patients refractory to ongoing PLT transfusion support. These antibodies are often IgG class switched, suggesting the involvement of CD4+ T-cell help; however, PLT-specific CD4+ T cells have not been visualized in vivo, and specifics of their stimulation are not completely understood. STUDY DESIGN AND METHODS: A murine model of alloimmunization to transfused PLTs was developed to allow in vivo assessment and characterization of CD4+ T cells specific for PLT major histocompatibility complex (MHC) alloantigen. PLTs were harvested from BALB/c mice, filter leukoreduced, and transfused into C57BL/6 recipients. PLT-specific CD4+ T-cell responses were visualized by using a T-cell receptor transgenic mouse that detects peptide from donor MHC I presented on recipient MHC II. Antibody responses were determined by indirect immunofluorescence using BALB/c donor targets. RESULTS: C57BL/6 recipients of BALB/c leukoreduced PLT transfusions produced BALB/c antibodies, with proliferation of antigen-specific CD4+ T cells seen in the spleen but not lymph nodes or liver. Depletion of recipient CD4+ cells or splenectomy independently abrogated the alloantibody response. CONCLUSION: We report a novel model to study antigen-specific CD4+ T cells during alloimmunization to PLT transfusion. The presented data support a critical role for CD4+ T-cell help in the humoral response to PLT transfusion and establish the spleen as a required microenvironment for effective CD4+ T-cell priming against donor PLT-derived MHC I. PMID- 21981243 TI - The role of self-efficacy in the wheelchair skills-physical activity relationship among manual wheelchair users with spinal cord injury. AB - PURPOSE: The purpose of this study was to determine whether self-efficacy can account for the relationship between wheelchair skills and leisure-time physical activity (LTPA) in people with spinal cord injury (SCI). METHOD: Fifty-four manual wheelchair users with SCI participated in this cross-sectional study. Participants completed a wheelchair skills test, and self-report measures of wheelchair-use self-efficacy, LTPA barrier self-efficacy, and LTPA. It was hypothesized that a positive wheelchair skills-LTPA relationship would be mediated by wheelchair-use self-efficacy and LTPA barrier self-efficacy. RESULTS: Using linear regression models, a positive association between wheelchair skills and LTPA was established (beta = 0.27, p < 0.05). LTPA barrier self-efficacy was a significant partial mediator, explaining 47.7% of the variance of the total relationship between skills and LTPA. Wheelchair-use self-efficacy was not a significant mediator of the wheelchair skills-LTPA relationship. CONCLUSIONS: Wheelchair skills play a modest role in LTPA participation and may facilitate LTPA, if skills help people feel more self-efficacious in their abilities to overcome LTPA barriers. The results have implications for understanding and improving LTPA participation. Improvements in wheelchair skills may facilitate LTPA, if people are taught the skills needed to increase their self-efficacy to overcome barriers to LTPA participation. PMID- 21981244 TI - Postprandial glycemia, insulinemia, and satiety responses in healthy subjects after whole grain rye bread made from different rye varieties. 2. AB - Rye breads made from commercial rye blends lower the postprandial insulin demand and appear to facilitate glucose regulation. However, differences in metabolic responses may occur between rye varieties. In the present work, five rye varieties (Amilo, Evolo, Kaskelott, Picasso. and Vicello) and a commercial blend of rye grown in Sweden were investigated with regard to their postprandial insulin, glucose, and appetite regulation properties in a randomized crossover study in 20 healthy subjects. The rye flours were baked into whole grain breads, and a white wheat bread (WWB) was used as reference (50 g of available starch). Picasso and Vicello rye bread showed lower glycemic indices (GIs) compared with WWB (80 and 79, respectively) (P < .0.05). In addition to the GI, two measures of the glycemic profile (GP and GP(2)) were calculated by dividing the incremental duration of the plasma glucose curve with the incremental glucose peak and squared incremental glucose peak, respectively. Vicello and Picasso ryes were characterized by a higher GP(2) than that of the WWB, suggesting a better regulated course of glycemia. Rye bread made from not only Vicello and Picasso but also Amilo and Kaskelott displayed significantly lower insulin indices (IIs) than WWB (74-82). A high GP and GP(2) and a low GI were related to a lower II and insulin incremental peak. A high content of insoluble fibers and a high GP(2) were related to a higher subjective satiety in the early and late postprandial phase (tAUC 0-60 min and tAUC 120-180 min, respectively). The results suggest that there may be differences in the course of glycemia following different rye varieties, affecting postprandial insulin responses and subjective satiety. PMID- 21981245 TI - Thermoelectric properties of lead chalcogenide core-shell nanostructures. AB - We present the full thermoelectric characterization of nanostructured bulk PbTe and PbTe-PbSe samples fabricated from colloidal core-shell nanoparticles followed by spark plasma sintering. An unusually large thermopower is found in both materials, and the possibility of energy filtering as opposed to grain boundary scattering as an explanation is discussed. A decreased Debye temperature and an increased molar specific heat are in accordance with recent predictions for nanostructured materials. On the basis of these results we propose suitable core shell material combinations for future thermoelectric materials of large electric conductivities in combination with an increased thermopower by energy filtering. PMID- 21981246 TI - The atypical cannabinoid O-1602 stimulates food intake and adiposity in rats. AB - AIMS: Cannabinoids are known to control energy homeostasis. Atypical cannabinoids produce pharmacological effects via unidentified targets. We sought to investigate whether the atypical cannabinoid O-1602 controls food intake and body weight. METHODS: The rats were injected acutely or subchronically with O-1602, and the expression of several factors involved in adipocyte metabolism was assessed by real-time polymerase chain reaction. In vivo findings were corroborated with in vitro studies incubating 3T3-L1 adipocytes with O-1602, and measuring intracellular calcium and lipid accumulation. Finally, as some reports suggest that O-1602 is an agonist of the putative cannabinoid receptor GPR55, we tested it in mice lacking GPR55. RESULTS: Central and peripheral administration of O-1602 acutely stimulates food intake, and chronically increases adiposity. The hyperphagic action of O-1602 is mediated by the downregulation of mRNA and protein levels of the anorexigenic neuropeptide cocaine- and amphetamine regulated transcript. The effects on fat mass are independent of food intake, and involve a decrease in the expression of lipolytic enzymes such as hormone sensitive lipase and adipose triglyceride lipase in white adipose tissue. Consistently, in vitro data showed that O-1602 increased the levels of intracellular calcium and lipid accumulation in adipocytes. Finally, we injected O-1602 in GPR55 -/- mice and found that O-1602 was able to induce feeding behaviour in GPR55-deficient mice. CONCLUSIONS: These findings show that O-1602 modulates food intake and adiposity independently of GPR55 receptor. Thus atypical cannabinoids may represent a novel class of molecules involved in energy balance. PMID- 21981250 TI - Sorafenib in hepatocellular carcinoma - a post marketing evaluation. AB - BACKGROUND: Sorafenib is an orally active multikinase inhibitor licensed for the treatment of patients with unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: The web-based registry, used for appraisal on new drugs, allows developing the observational prospective analysis of innovative drug therapies. To establish clinical impact of Sorafenib, institutional data were collected prospectively through the registry. RESULTS: A total of 81 patients treated with Sorafenib were reviewed (median age = 65 years) and the follow-up duration was 30 months. Every patient was checked for length of treatment, toxicity and outcomes. Based on the study sample, the median time to progression was 3 months and median overall survival was 8 months. We found 52% progressions at first evaluation and the disease control rate was 32%. CONCLUSION: Our data from real life practice showed that the clinical benefit of Sorafenib in unresectable HCC was gained in selected responder patients. PMID- 21981263 TI - Identification of a phenanthrene derivative as a potent anticancer drug with Pim kinase inhibitory activity. AB - Pim-3, a proto-oncogene with serine/threonine kinase activity, is aberrantly expressed in malignant lesions, but not in normal tissues, of endoderm-derived organs, including the pancreas, liver, colon, and stomach. Furthermore, the development of hepatocellular carcinoma is accelerated in mice expressing Pim-3 transgene selectively in the liver when these mice are treated with a hepatocarcinogen. These observations suggest that a chemical targeting Pim-3 kinase may be a novel type of anticancer drug. In the present study, we screened low molecular weight chemicals and observed that the phenanthrene derivative T26 potently inhibited Pim-3 and Pim-1, but only weakly inhibited Pim-2. Moreover, T26 markedly inhibited the in vitro growth of human pancreatic cancer cell lines by inducing apoptosis and G(2) /M arrest. The growth inhibitory effects of T26 were reversed by overexpression of Pim-3 cDNA in human pancreatic cancer cells, indicating that T26 acts primarily on Pim-3. Furthermore, T26 inhibited the growth of a human pancreatic cancer cell line in nude mice without causing apparent adverse effects when it was administered after tumor formation was evident. These observations imply that the chemical and its related compounds may be effective for the treatment of cancers in which there is aberrant Pim-3 expression. PMID- 21981264 TI - Probing the interaction of cisplatin with the human copper chaperone Atox1 by solution and in-cell NMR spectroscopy. AB - Among anticancer therapeutics, platinum-based drugs have a prominent role. They carry out their antitumor activity by forming stable adducts with DNA, thus interfering with replication and transcription processes. Cellular uptake of these drugs is tightly connected to copper transport. The major Cu(I) influx transporter Ctr1 has been found to mediate transport of cisplatin and its analogues. Evidence also suggests that ATP7A and ATP7B mediate cisplatin sequestration and efflux from cells, thus influencing drug resistance. The copper chaperone Atox1, which normally binds Cu(I) via two cysteines and delivers the metal to ATP7A/B, has also been reported to interact with cisplatin in in vitro experiments. In the present investigation we apply a combined approach, using solution and in-cell NMR spectroscopy methods, to probe intracellular drug delivery and interaction of cisplatin with Atox1. The intracellular environment provides itself the suitable conditions for the preservation of the protein in its active form. Initially a {Pt(NH(3))(2)}-Atox1 adduct is formed. At longer reaction time we observed protein dimerization and loss of the ammines. Such a process is reminiscent of the copper-promoted formation of Atox1 dimers which have been proposed to be able to cross the nuclear membrane and act as a transcription factor. We also show that overexpression of Atox1 in E. coli reduces the amount of DNA platination and, consequently, the degree of cell filamentation. PMID- 21981265 TI - Efficient oxidation of cysteine and glutathione catalyzed by a dinuclear areneruthenium trithiolato anticancer complex. AB - The highly cytotoxic diruthenium complex [(p-MeC(6)H(4)Pr(i))(2)Ru(2)(SC(6)H(4)-p Me)(3)](+) (1), water-soluble as the chloride salt, is shown to efficiently catalyze oxidation of the thiols cysteine and glutathione to give the corresponding disulfides, which may explain its high in vitro anticancer activity. PMID- 21981266 TI - Comparative analysis of crystallinity changes in cellulose I polymers using ATR FTIR, X-ray diffraction, and carbohydrate-binding module probes. AB - Cotton fiber cellulose is highly crystalline and oriented; when native cellulose (cellulose I) is treated with certain alkali concentrations, intermolecular hydrogen bonds are broken and Na-cellulose I is formed. At higher alkali concentrations Na-cellulose II forms, wherein intermolecular and intramolecular hydrogen bonds are broken, ultimately resulting in cellulose II polymers. Crystallinity changes in cotton fibers were observed and assigned using attenuated total reflectance Fourier transform infrared (ATR FT-IR) spectroscopy and X-ray diffraction (XRD) subsequent to sodium hydroxide treatment and compared with an in situ protein-binding methodology using cellulose-directed carbohydrate binding modules (CBMs). Crystallinity changes observed using CBM probes for crystalline cellulose (CBM2a, CBM3a) and amorphous cellulose (CBM4-1, CBM17) displayed close agreement with changes in crystallinity observed with ATR-FTIR techniques, but it is notable that crystallinity changes observed with CBMs are observed at lower NaOH concentrations (2.0 mol dm(-3)), indicating these probes may be more sensitive in detecting crystallinity changes than those calculated using FTIR indices. It was observed that the concentration of NaOH at which crystallinity changes occur as analyzed using the CBM labeling techniques are also lower than those observed using X-ray diffraction techniques. Analysis of crystallinity changes in cellulose using CBMs offers a new and advantageous method of qualitative and quantitative assessment of changes to the structure of cellulose that occur with sodium hydroxide treatment. PMID- 21981267 TI - Cord blood transplantation in Western Australia. AB - BACKGROUND/AIMS: Thirty-one umbilical cord blood transplants performed in Western Australia were retrospectively examined in order to document local experience and relevant prognostic factors. Three cord units were from human leucocyte antigen matched siblings and the remainder were unrelated single (n= 22) or double (n= 6) cord blood transplants. METHODS: Twenty patients were transplanted for malignant conditions and 11 for non-malignant conditions. Cord units contained a median of 5.6 * 107 total nucleated cells/kg and 1.4 * 105 CD34+ cells/kg. Cumulative incidence of neutrophil engraftment was 76% at day 60. RESULTS: Of those who did not engraft, two patients remain alive following subsequent allogeneic bone marrow transplant. There were no deaths caused by graft-versus-host disease. Overall survival at median follow up of 28 months was 62%. Two year overall survival was influenced by type of disease (non-malignant = 91 +/- 9% vs malignant = 41 +/- 13%, P= 0.005), total nucleated cell dose (>3.5 * 107/kg = 87 +/- 9% vs <3.5 * 107/kg = 34 +/- 15%, P= 0.01) and CD34 dose (>1.7 * 105/kg = 92% vs <1.7 * 105/kg = 46%, P= 0.04). Age and human leucocyte antigen match did not influence survival. Four relapses occurred, all of which were fatal. CONCLUSION: Cord blood transplantation for malignant and non-malignant disease is practised in Western Australia and outcomes are satisfactory. Trends and techniques in cord blood transplantation in this state are comparable with those observed nationally and overseas. Although numbers are small, cell dose appears to be predictive of overall survival PMID- 21981268 TI - Lack of association of IL6R rs2228145 and IL6ST/gp130 rs2228044 gene polymorphisms with cardiovascular disease in patients with rheumatoid arthritis. AB - Interleukin-6 (IL-6) is a key mediator of inflammation in rheumatoid arthritis (RA) and its actions may be controlled by the IL-6 receptor (IL-6R). IL-6 transducer (IL-6ST/ gp130) is the signal transducing subunit of the IL-6R. We assessed the influence of the IL6R and the IL6ST/gp130 genes in the risk of cardiovascular (CV) disease in RA. For this purpose, 1250 Spanish patients with RA were genotyped for the IL6R rs2228145 and IL6ST/gp130 rs2228044 functional gene polymorphisms. Patients were stratified according to the presence or absence of CV events. Also, a subgroup of patients without CV events was assessed for the presence of subclinical atherosclerosis using two surrogate markers of atherosclerosis (flow-mediated endothelium-dependent vasodilatation and carotid intima-media thickness). No significant differences in the genotype and allele frequencies for both gene polymorphisms between patients with and without CV events were observed. It was also the case when values of surrogate markers of atherosclerosis were compared according to IL6R and IL6ST genotype frequencies. In conclusion, our results do not confirm an association of IL6R rs2228145 and IL6ST/gp130 rs2228044 polymorphisms with CV disease in RA. PMID- 21981269 TI - Serum S100B and neuron-specific enolase levels in normothermic and hypothermic infants after perinatal asphyxia. AB - AIM: Serum S100B and neuron-specific enolase (NSE) levels are elevated after perinatal asphyxia, but the influence of hypothermia on these proteins has not been previously reported. The aim of this study was to evaluate the effect of systemic hypothermia on these protein levels after perinatal asphyxia, time course, and association with perinatal factors and neurodevelopmental outcome at 2 years of age. METHODS: Serum S100B and NSE levels were measured at fixed time points in asphyxiated infants treated with standard intensive care on hypothermia (HT: n = 13) or normothermia (NT: n = 11). RESULTS: Serum S100B and NSE levels were grossly elevated in both HT and NT groups. Compared with the values at 6 h of age, S100B values decreased over time in both groups (NT: p = 0.002, HT: p = 0.04). Serum S100B values were lower in HT infants compared with those in NT infants (p = 0.047 at 48 h). Serum S100B and NSE values were significantly higher in infants who died or developed severe neurological impairment (S100B, p < 0.05 at all time points; NSE, p = 0.036 at 24 h of age). CONCLUSION: Both NSE and S100B levels are highly elevated following asphyxia. Serum S100B levels were lower in the HT group and strongly correlated with the neurodevelopmental outcome. PMID- 21981271 TI - Spontaneous pneumarthrosis of the atlantoaxial joint. AB - The authors describe the case of a 29-year-old man presenting with left retrooccipital and cervical pain associated with left ear fullness and rhythmic tinnitus. Head rotation movements on the right side and the Valsalva maneuver increased symptoms. A CT scan identified hyperpneumatization of the left temporal bone extending to the occipital bone as well as pneumarthrosis of the atlantoaxial joint. Surgical treatment involving obliteration of the fistula with bone and fat grafts via a computer-aided transmastoid approach was proposed. The surgery resolved all of the patient's symptoms except for the ear fullness. In this case the authors described an original treatment for spontaneous atlantoaxial pneumarthrosis. Long-term follow-up is needed to evaluate the risk of the recurrence of abnormal occipital bone pneumatization and to assess joint function. PMID- 21981270 TI - Phosphorylated Syk expression is enhanced in Nasu-Hakola disease brains. AB - Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder, characterized by progressive presenile dementia and formation of multifocal bone cysts, caused by a loss-of-function mutation of DNAX-activation protein 12 (DAP12) or triggering receptor expressed on myeloid cells 2 (TREM2). TREM2 and DAP12 constitute a receptor/adaptor complex on myeloid cells. The post-receptor signals are transmitted via rapid phosphorylation of the immunoreceptor tyrosine-based activating motif (ITAM) of DAP12, mediated by Src protein tyrosine kinases, followed by binding of phosphorylated ITAM to Src homology 2 (SH2) domains of spleen tyrosine kinase (Syk), resulting in autophosphorylation of the activation loop of Syk. To elucidate the molecular mechanism underlying the pathogenesis of NHD, we investigated Syk expression and activation in the frontal cortex and the hippocampus of three NHD and eight control brains by immunohistochemistry. In NHD brains, the majority of neurons expressed intense immunoreactivities for Syk and Y525/Y526-phosphorylated Syk (pSyk) chiefly located in the cytoplasm, while more limited populations of neurons expressed Src. The levels of pSyk expression were elevated significantly in NHD brains compared with control brains. In both NHD and control brains, substantial populations of microglia and macrophages expressed pSyk, while the great majority of reactive astrocytes and myelinating oligodendrocytes did not express pSyk, Syk or Src. These observations indicate that neuronal expression of pSyk was greatly enhanced in the cerebral cortex and the hippocampus of NHD brains, possibly via non-TREM2/DAP12 signaling pathways involved in Syk activation. PMID- 21981272 TI - Surgical management of unknown primary tumors metastatic to the spine. AB - OBJECT: Patients presenting with spinal metastases from unknown primary tumors (UPTs) are rare. The authors reviewed their surgical experience to evaluate outcomes and identify predictors of survival in these patients. METHODS: This study is a retrospective analysis of patients undergoing surgery for metastatic spine disease from UPTs between June 1993 and February 2007 at The University of Texas M. D. Anderson Cancer Center. RESULTS: Fifty-one patients undergoing 52 surgical procedures were identified. The median age at spine surgery was 60 years. The median survival from time of diagnosis was 15.8 months (95% CI 8.1 23.6) and it was 8.1 months (95% CI 1.6-14.7) from time of spine surgery. Postoperative neurological function (Frankel score) was the same or improved in 94% of patients. At presentation, 77% had extraspinal disease, which was associated with poorer survival (6.4 vs 18.1 months; p = 0.041). Multiple sites (vs a single site) of spine disease did not impact survival (12.7 vs 8.7 months; p = 0.50). Patients with noncervical spinal disease survived longer than those with cervical disease (11.8 vs 6.4 months, respectively; p = 0.029). Complete versus incomplete resection at index surgery had no impact on survival duration (p > 0.5) or local recurrence (p = 1.0). Identification of a primary cancer was achieved in 31% of patients. CONCLUSIONS: This is the first reported surgical series of patients with an unknown source of spinal metastases. The authors found that multiple sites of spinal disease did not influence survival; however, the presence of extraspinal disease had a negative impact. The extent of resection had no effect on survival duration or local recurrence. With an overall median survival of 8.1 months following surgery, aggressive evaluation and treatment of patients with metastatic disease of the spine from an unknown primary source is warranted. PMID- 21981273 TI - Spondylectomy of T-2 according to the Tomita technique via an extended Fessler approach: a cadaveric study. AB - OBJECT: The authors' aim was to conduct a surgical anatomy and feasibility study on the use of an extended posterolateral approach to the cervicothoracic junction (Fessler approach) in cadavers to facilitate en bloc removal of the second thoracic vertebra using the Tomita technique. To apply this technique, it is mandatory to approach both sides of the vertebra. But such a maneuver is very difficult in the region of the cervicothoracic junction because the scapula and its muscles represent an anatomical barrier to the paravertebral compartment and lateral aspects of the vertebrae. METHODS: To study the extended posterolateral Fessler approach to the cervicothoracic junction and the possible application of the Tomita technique on the second thoracic vertebra, 3 fresh-frozen cadavers were used in the Laboratory of Human Anatomy at the University of Nantes. RESULTS: The proposed approach allows exposure of both the posterior arch and the body of the second thoracic vertebra without any significant resection or traction of the superficial and deep posterior thoracic muscles, enabling application of the Tomita technique and facilitating intraoperative spinal fixation. CONCLUSIONS: The proposed surgical technique is technically feasible. Nevertheless, it should be an option reserved for selected patients for whom the surgical complexity can be justified by the characteristics of their malignancy and expected curative outcome. PMID- 21981274 TI - Prospective cohort study of mild cervical spondylotic myelopathy without surgical treatment. AB - OBJECT: Because the main pathology of cervical spondylotic myelopathy (CSM) is spinal cord damage due to compression, surgical treatment is usually recommended to improve patient symptoms and prevent exacerbation. However, lack of clarity of prognosis in cases that present with insignificant symptoms, particularly those of mild CSM, lead one to question the veracity of this course of action. The purpose of this study was to elucidate the prognosis of mild CSM without surgical intervention by evaluation of clinical symptoms and MR imaging findings. METHODS: Sixty cases of mild CSM (42 males and 18 females, average age 57.2 years) presenting with scores of 13 or higher on the Japanese Orthopaedic Association (JOA) scale were treated initially by in-bed Good Samaritan cervical traction without surgery. These patients were enrolled between 1995 and 2003 and followed up periodically until the date of myelopathy deterioration or until the end of March 2009. The deterioration of myelopathy was defined as a decline in JOA score to less than 13 with a decrease of at least 2 points. As a prognostic factor, the authors used their classification of spinal cord shapes at their lateral sides on axial T1-weighted MR imaging. "Ovoid deformity" was classified as a situation in which both sides were round and convex, and "angular-edged deformity" where one or both sides exhibited an acute-angled lateral corner. The duration of follow-up was assessed as the tolerance rate of mild CSM using Kaplan-Meier survival analysis and compared between 2 groups classified by MR imaging findings. Furthermore, differences between groups were analyzed by various applications of the log-rank test. RESULTS: Of the initial 60 cases, follow-up records existed for 55, giving a follow-up rate of 91.7% (38 males and 17 females, average age 56.1 years). The mean JOA score at end point was 14.1, which was not statistically different from the mean of 14.5 at the initial visit. Deterioration in myelopathy was observed in 14 (25.5%) of 55 cases, whereas 41 (74.5%) of 55 cases maintained mild extent myelopathy without deterioration through the follow up period (mean 94.3 months). The total tolerance rate of mild CSM was 70%. However, there was a significant difference in the tolerance rate between the cases with angular-edged deformity (58%) and cases with ovoid deformity (95%; p = 0.049). CONCLUSIONS: The tolerance rate of mild CSM was 70% in this study, which proved that the prognosis of mild CSM without surgical treatment was relatively good. However, the tolerance rate of the cases with angular-edged deformity was 58%. Therefore, surgical treatment should be considered when mild CSM cases show angular-edged deformity on axial MR imaging, even if patients lack significant symptoms. PMID- 21981275 TI - Laparoscopic skills training using inexpensive box trainers: which exercises to choose when constructing a validated training course. AB - OBJECTIVE: To obtain face and construct validity for a new training course to be used in any type of box/video trainer and to give a comprehensive overview of validated exercises for box/video training. DESIGN: Cross-sectional study. SETTING: University Medical Centre. POPULATION: Students, residents and consultants. METHODS: Participants (n = 42) were divided into three groups according to their laparoscopic experience: 'Novices' (n = 18), 'Intermediates' (n = 14) and 'Experts' (n = 10). A laparoscopic training course consisting of six exercises was constructed. To emphasise precision, a penalty score was added. Every participant performed two repetitions of the exercises; total score per exercise was calculated. To determine face validity, participants filled in a questionnaire after completion of the exercises. An evidence-based literature search for validated box/video trainer exercises was performed. MAIN OUTCOME MEASURES: Face and construct validity. RESULTS: The mean score of the 'experts' was set as the training target. Total scores appeared to be positively correlated with individual's laparoscopic experience. The overall score and the score for each exercise were significantly higher in the intermediate and expert groups when compared with the novice group (P <= 0.001). All participants completed the questionnaire. The overall assessment of the exercises was considered to be good. The course was found to be most appropriate for training residents year 1-3. CONCLUSION: Face and construct validity for an inexpensive course for box/video training was established. A comprehensive and practical overview of all validated and published exercises for box/video trainers is provided to facilitate an inexpensive, but optimal and tailored selection for training purposes. PMID- 21981277 TI - Oxytocin revisited: its role in cardiovascular regulation. AB - Traditionally associated with female reproduction, oxytocin (OT) was revisited recently and was revealed to have several new roles in the cardiovascular system. Functional OT receptors have been discovered in the rat and human heart, as well as in vascular beds. The cardiovascular activities of OT include: (i) lowering blood pressure; (ii) negative cardiac inotropy and chronotropy; (iii) parasympathetic neuromodulation; (iv) vasodilatation; (v) anti-inflammatory; (vi) antioxidative; and (vii) metabolic effects. These outcomes are mediated, at least in part, by stimulating cardioprotective mediators, such as nitric oxide and atrial natriuretic peptide. OT and its extended form OT-Gly-Lys-Arg have been shown to be abundant in the foetal mouse heart. OT has the capacity to generate cardiomyocytes from various types of stem cells, including the cardiac side population. Mesenchymal cells transfected with OT-Gly-Lys-Arg, or preconditioned with OT, are resistant to apoptosis and express endothelial cell markers. OT increases glucose uptake in cultured cardiomyocytes from newborn and adult rats, in normal, hypoxic and even insulin resistance conditions. In rats with experimentally-induced myocardial infarction, continuous in vivo OT delivery improves the cardiac healing process, as well as cardiac work, reduces inflammation and stimulates angiogenesis. Therefore, in pathological conditions, OT exerts anti-inflammatory and cardioprotective properties, and improves vascular and metabolic functions. Thus, OT has potential for therapeutic use. PMID- 21981279 TI - Efficient charge separation in multidimensional nanohybrids. AB - We report unidirectional charge transfer in multidimensional nanohybrids, consisting of a quantum dot, an electronically active molecular linker, and a carbon nanotube. After covalent attachment to the nanotube, only emission consistent with the negatively charged quantum dot exciton ion rather than the neutral exciton is observed, showing nearly monoexponential recombination kinetics and an average lifetime of 3.5 ns. Using kinetic models, we explain how charge transfer is biased at the expense of other decay pathways. PMID- 21981280 TI - Preparation of commercial quantities of a hyperimmune human intravenous immunoglobulin preparation against an emerging infectious disease: the example of pandemic H1N1 influenza. AB - BACKGROUND: The recent H1N1 pandemic provided an opportunity to conceptually assess the possibility of rapidly providing a "hyperimmune" human immunoglobulin (H-IVIG) to an emerging infectious disease, in useful quantities with respect to public health. Commercial-scale H-IVIG production from plasma collected from donors convalescent from or vaccinated against pandemic influenza A (H1N1) virus is described. STUDY DESIGN AND METHODS: A special protocol was implemented for the collection, processing, and shipment of plasma from previously qualified source plasma donors, self-identifying as convalescent from or vaccinated against H1N1 influenza. A licensed IVIG manufacturing process was utilized for the preparation of two commercial lots of approximately 50 kg 10% human IVIG preparation in total. The H1N1 hemagglutination inhibition and neutralization antibody titers of the resulting H-IVIG preparations were determined and compared with standard preparations. RESULTS: Twenty-six plasma collection centers participated in the protocol. Donor enrollment exceeded 300 donors per week and within 30 days of protocol deployment plasma was being collected at a rate of more than 2000 L/week. Manufacture of both H-IVIG lots was unremarkable and both lots met the requirements for commercial release and the bulk of the product was distributed in normal commercial channels. Examination of plasma pools and final IVIG product confirmed pandemic H1N1 antibody titers substantially higher than those collected before the emergence of the pandemic H1N1 virus. CONCLUSIONS: This work demonstrates the feasibility of producing a H-IVIG preparation at large scale relatively rapidly, with a significant enrichment in antibodies to the H1N1 influenza, achieved by donor self-identification. PMID- 21981281 TI - Lycopene bioaccessibility and starch digestibility for extruded snacks enriched with tomato derivatives. AB - To improve the nutritional value of energy-dense extruded snacks, corn grits were replaced with tomato paste and/or tomato skin powder at ratios of 5, 10, and 20% and extruded to make expanded snack foodlike products. Using a model digestion system, lycopene bioaccessibility and uptake from the snacks into Caco-2 cells were determined. The digestibility of the starch, the main nutrient component of the snacks, was also investigated. While extrusion cooking reduced the lycopene content of the snacks, the proportion of bioaccessible lycopene increased. Lycopene uptake by the Caco-2 cells from the extruded snacks exceeded that of the control in which the lycopene was not extruded, by 5% (p < 0.05). The digestibility of starch in the snacks varied depending on the type of tomato derivative and its concentration. Optimization of the extrusion cooking process and the ingredients can yield functional extruded snack products that contain bioavailable lycopene. PMID- 21981282 TI - Sex determination from the talus of Koreans by discriminant function analysis. AB - The aims of this study were to investigate the sex discriminating potential of the talus in Koreans and compare this with other analyses in different populations. Statistical analyses were performed using data from nine measurements acquired from 140 tali (70 men, 70 women). The talus of Koreans is dimorphic between sexes in all measurements (p < 0.01). Discriminant function equations were generated by univariate, multivariate, and stepwise methods with a range of accuracy from 67.1 to 87.1%. Stepwise equations of other populations did not discriminate the sex of the Korean sample as accurately as each equation's own accuracies. The variables with high accuracy in this study are useful for sex determination of Koreans on the basis of confirmation of population specificity. PMID- 21981278 TI - Mammalian TOR signaling to the AGC kinases. AB - The mechanistic (or mammalian) target of rapamycin (mTOR), an evolutionarily conserved protein kinase, orchestrates cellular responses to growth, metabolic and stress signals. mTOR processes various extracellular and intracellular inputs as part of two mTOR protein complexes, mTORC1 or mTORC2. The mTORCs have numerous cellular targets but members of a family of protein kinases, the protein kinase (PK)A/PKG/PKC (AGC) family are the best characterized direct mTOR substrates. The AGC kinases control multiple cellular functions and deregulation of many members of this family underlies numerous pathological conditions. mTOR phosphorylates conserved motifs in these kinases to allosterically augment their activity, influence substrate specificity, and promote protein maturation and stability. Activation of AGC kinases in turn triggers the phosphorylation of diverse, often overlapping, targets that ultimately control cellular response to a wide spectrum of stimuli. This review will highlight recent findings on how mTOR regulates AGC kinases and how mTOR activity is feedback regulated by these kinases. We will discuss how this regulation can modulate downstream targets in the mTOR pathway that could account for the varied cellular functions of mTOR. PMID- 21981283 TI - Chemical composition and antioxidant activity of the essential oil of Schisandra chinensis fruits. AB - This study was designed to examine the composition and in vitro antioxidant activity of the essential oil of Schisandra chinensis fruits. Gas chromatography/mass spectrometry was used to determine the composition of the essential oil. Forty components were identified, representing 90.80% of the oil; ylangene (37.72%), beta-himachalene (10.46%) and alpha-bergamotene (8.57%) were the main components. Antioxidant and radical-scavenging properties were evaluated by means of 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and beta-carotene bleaching assay. In the DPPH assay, IC(50) value of the S. chinensis essential oil was determined as 4.17 mg mL(-1). In the beta-carotene bleaching assay, the essential oil (1.0 mg mL(-1)) exhibited 25.89% inhibition against linoleic acid oxidation. In both systems, antioxidant capacity of butylated hydroxytoluene was also determined in parallel experiments. PMID- 21981284 TI - Chinese translation and validation of the Kujala scale for patients with patellofemoral pain. AB - PURPOSE: This study translated and validated the Kujala scale, a well-documented questionnaire for patients with patellofemoral pain, into Chinese version. METHOD: Chinese Kujala scale was translated from the original English version following the recommendations of the International Society for Pharmacoeconomics and Outcomes Research. Sixty four Chinese reading patients who are diagnosed of patellofemoral pain were recruited from multiple hospitals and physiotherapy clinics. Psychometric property was evaluated in terms of test-retest reliability and internal consistency. Convergent validity was examined by Spearman rank correlation coefficient tests by comparing its score with the validated Chinese version of WOMAC Osteoarthritis Index and SF-36. RESULTS: Chinese Kujala scale demonstrated excellent reliability (ICC = 0.968, p < 0.001). Cronbach's alpha of individual questions and its overall value were above 0.7. Strong correlation was found between the Chinese Kujala scale and the WOMAC Osteoarthritis Index (rho = 0.708, p < 0.001). Fairly weak correlations were also found between Chinese Kujala scale with the "physical" (rho = 0.413-0.498, p < 0.001) and "energy vitality" (rho = 0.290, p = 0.02) domains of SF-36. However, the relationship between the "bodily pain" was not significant (rho = 0.136, p = 0.284). CONCLUSION: The Chinese translated version of Kujala scale is a reliable and valid instrument for assessing the patellofemoral pain associated functional disturbances among the patient cohort. PMID- 21981285 TI - Biological validation that SF3b is a target of the antitumor macrolide pladienolide. AB - Pladienolide is a naturally occurring macrolide that binds to the SF3b complex to inhibit mRNA splicing. It has not been fully validated whether the splicing impairment is a relevant mechanism for the potent antitumor activity of pladienolide. We established pladienolide-resistant clones from WiDr and DLD1 colorectal cancer cells that were insensitive to the inhibitory action of pladienolide on cell proliferation and splicing. An mRNA-Seq differential analysis revealed that these two cell lines have an identical mutation at Arg1074 in the gene for SF3B1, which encodes a subunit of the SF3b complex. Reverse expression of the mutant protein transferred pladienolide resistance to WiDr cells. Furthermore, immunoprecipitation analysis using a radiolabeled probe showed that the mutation impaired the binding affinity of paldienolide to its target. These results clearly demonstrate that pladienolide exerts its potent activity by targeting SF3b and also suggest that inhibition of SF3b is a promising drug target for anticancer therapy. PMID- 21981286 TI - U-100, pH-Neutral formulation of VIAject((r)) : faster onset of action than insulin lispro in patients with type 1 diabetes. AB - AIMS: VIAject(r) is a formulation of human insulin with a very fast onset of action. Previous studies used VIAject in a concentration of 25 U/ml and a pH of 4 [VIAject 25 (VJ25)]. Objective of this double blind, three-way crossover study was to compare the pharmacodynamic/pharmacokinetic properties of a novel formulation of VIAject with a concentration of 100 U/ml and a neutral pH [VIAject 7 (VJ7)] with VJ25 and insulin lispro (LIS). METHODS: Forty-three patients with type 1 diabetes [aged 43 (21-65) years, BMI 24.1 (20-28) kg/m(2) and HbA1c 7.5 (5.7-9.5) %] participated in this study. They received subcutaneous injections of 12 U of each insulin formulation under euglycaemic glucose clamp conditions. RESULTS: VJ7 was bioequivalent to VJ25 [90% confidence interval (CI) of the ratios for total insulin AUCs and maximum insulin concentration (C(INS max) ) was within 0.80-1.25]. VJ7 showed a faster absorption compared to LIS [time to C(INS max) 23 vs. 60 min; difference (CI) -30 (-35 to -23)] and faster onset of action [time to early half-maximal glucose infusion rate (GIR) 25 vs. 44 min; -18 (-26 to -10)], and a higher AUC of glucose infusion rate (AUC(GIR) ) in the first 60 min after injection [176 vs. 107 mg/kg; ratio 1.65 (1.27 to 2.14)], contributing to a slightly higher value for AUC(GIR 0-480) [1263 vs. 1095 mg/kg; 1.15 (1.06 to 1.26)]. Maximum GIR was similar between VJ7 and LIS [6.1 vs.6.6 mg/kg/min; ratio 0.93 (0.86 to 1.01)], whereas the duration of action (t(GIR50%-late) ) was longer with VJ7 [274 vs. 228 min; 50 (25 to 73)]. CONCLUSIONS: This formulation of VIAject is bioequivalent to the previously used formulation and has a faster absorption/onset of action than LIS. PMID- 21981303 TI - Cathodic corrosion as a facile and effective method to prepare clean metal alloy nanoparticles. AB - The cathodic corrosion method described here is a simple, clean, and fast way of synthesizing nanoalloys with high catalytic performance. Using a series of Pt-Rh alloys as an example, we show that this one-step method can convert a bulk alloy electrode into an aqueous suspension of nanoparticles, retaining the composition and crystal lattice structure of the starting alloy. Compared to pure metals, these alloy nanocatalysts are more active toward CO and methanol oxidation and nitrate reduction reactions. Nanoparticles made of PtRu, PtIr, PtNi, AuCo, AuCu, and FeCo bulk alloys demonstrate the universality of this synthesis method. PMID- 21981302 TI - Colonic butyrate- algesic or analgesic? AB - Irritable bowel syndrome (IBS) is a common health issue that is characterized by abdominal pain, abnormal bowel movements, and altered visceral perception. The complexity and variability in symptoms pose serious challenges in treating IBS. Current therapy for IBS is primarily focused on reducing the abdominal pain, thereby improving the quality of life to a significant extent. Although the use of fiber rich diet is widely recommended in treating IBS, some studies have questioned its use. Intra-colonic butyrate, a short-chain fatty acid, is primarily produced by the fermentation of dietary fibers in the colon. In the existing literature there are conflicting reports about the function of butyrate. In rats it is known to induce visceral hypersensitivity without altered pathology, whereas in humans it has been reported to reduce visceral pain. Understanding the molecular mechanisms responsible for this contrasting effect of butyrate is important before recommending fiber rich diet to IBS patients. PMID- 21981304 TI - Structure and bonding of KSiH3 and its 18-crown-6 derivatives: unusual ambidentate behavior of the SiH3(-) anion. AB - Density functional theory (DFT) calculations of [K(18-crown-6)SiH(3)] (1) and KSiH(3) (2) have shown that both the classical tet and non-classical inv coordination modes of the [SiH(3)](-) anion to the K(+) ion are energetically accessible. Single-crystal X-ray structures of the tet and inv derivatives [K(18 crown-6)SiH(3).THF] (1a) and [K(18-crown-6)SiH(3).HSiPh(3)] (1b) confirm this conclusion, showing that small changes in the coordination sphere of the metal are sufficient to alter the orientation of the anion. A topological analysis of the calculated electron densities for 1 and 2 reveals that the K...Si interaction in the tet conformer of 2 possesses a significant amount of covalent character. In contrast, the inv form of 2 displays primarily electrostatic character for the K...Si and K...H interactions. Incorporation of the 18-crown-6 ligand in 1 reduces the polarizing power of the K(+) cation, hardening the cation-anion interaction in both conformers. The experimental structures of 1a and 1b bear out these conclusions, with the strongly bound tetrahydrofuran (THF) ligand softening the K(+) ion in 1a and favoring the tet conformer, while the weakly interacting HSiPh(3) ligand in 1b has minimal effect on the K(+) center, resulting in an inv orientation. PMID- 21981305 TI - Effect of incoherent LED radiation on third-degree burning wounds in rats. AB - The main physiological characteristics in a burn process are the increase of the capillary permeability and the occurrence of edema and exudation. Light-emitting diode (LED) has been proposed as treatment of burning. This study investigated the effects of LED on the repair process of rat skin submitted to a third-degree burning. The lesions were produced on the dorsal surface of male Wistar rats. Animals were divided into 4 groups (n = 6) as follows: L1 and L2 groups as LED treated burned rats, and received LED therapy along 7 and 15 days with 48 hours intervals, respectively; C1 and C2 groups as control, non-treated burned rats. A red LED (640 nm, 30 mW) operating with a fluence of 4 J/cm(2) was used. The wound area was measured daily after irradiation. Animals were euthanized at the 8th and 16th days after burning, and the wound fragment was submitted to histology. The inflammatory cells as well as the damaged area at the 8th day after burns were significantly lower for the LED-treated group when compared to control. Furthermore, the LED phototherapy effect on cellular migration was even more pronounced at the 16th day. Our results indicated that the treatment with a LED system was clearly effective in reducing the number of inflammatory cells and improving the healing process in an experimental model of third-degree burnings. PMID- 21981306 TI - Elevated genetic diversity of mitochondrial genes in asexual populations of Bark Lice ('Psocoptera': Echmepteryx hageni). AB - Asexual reproduction is commonly thought to be associated with low genetic diversity in animals. Echmepteryx hageni (Insecta: 'Psocoptera') is one of several psocopteran species that are primarily parthenogenetic, but also exists in small, isolated sexual populations. We used mitochondrial DNA sequences to investigate the population history and genealogical relationships between the sexual and asexual forms of this species. The asexual population of E. hageni exhibits extremely high mitochondrial haplotype diversity (H=0.98), whereas the sexual forms had significantly lower haplotypic diversity (H=0.25, after correcting for sample size). This diversity in asexuals represents one the greatest genetic diversities reported for asexual animals in the literature. Nucleotide diversities were also higher in asexual compared to sexual populations (pi=0.0071 vs. 0.00027). Compared to other reported estimates of pi in insects, asexual nucleotide diversity is high, but not remarkably elevated. Three hypotheses might explain the elevated genetic diversity of asexual populations: (i) larger effective population size, (ii) greater mutation rate or (iii) possible recent origin of sexuals. In addition, phylogeographic analysis revealed little geographic structure among asexual E. hageni, although specimens from the upper Midwest form a single clade and are genetically differentiated. The mismatch distribution and neutrality tests indicate a historical population size increase, possibly associated with expansion from glacial refugia. PMID- 21981307 TI - Reliability, sensitivity and responsiveness of the Infant Behavioral Assessment in very preterm infants. AB - AIM: The aim of this study is to investigate the reliability, sensitivity and responsiveness of the Infant Behavioral Assessment (IBA) to evaluate neurobehavioural organization in very preterm infants. METHODS: Videotaped assessments of very preterm infants participating in a recent trial served to evaluate a standardized IBA observation. Inter-rater reliability was based on 40 videos scored by two independent observers, using percentage agreement and weighted Kappa's. Sensitivity was evaluated by comparing the IBA results of 169 infants at 35-38 weeks postmenstrual age, dichotomized according to two developmental risk factors. For responsiveness, the effect size (ES) was calculated between 0 and 6 months corrected age in all intervention and control infants and in subgroups of high-risk intervention and control infants with oxygen dependency >=28 days. RESULTS: Inter-rater agreement was 93% in the total assessment; Kappa agreement was moderate to good in the behavioural categories. Significant differences were found between groups with or without risk factors. Larger differences between ESs in the randomized groups with oxygen dependency >=28 days than in the total randomized groups reflect the responsiveness of the IBA. CONCLUSION: In this study, we found satisfactory to good clinimetric characteristics of the IBA in very preterm born infants. PMID- 21981308 TI - Patient perceptions of medical students' involvement in their obstetrics and gynaecology health care. AB - OBJECTIVE: To determine perceptions held by patients of the involvement of medical students in their obstetrics and gynaecology health care. STUDY DESIGN: This study evaluated patients' perceptions of medical students involved in their care at a tertiary women's hospital. A questionnaire was used to collect patients' perceptions of the student's professional skills, their attitude to and level of comfort in the patient and student interaction. RESULTS: Ninety-five percent of patients approached participated in this study. Results demonstrated a high level of patient satisfaction with student involvement in care. Most patients believed students should be part of the hospital team and were prepared to have a student involved in the future. Satisfaction levels were higher for patients for whom English was their first language, women under 40 years of age and those receiving care in assessment and in-patient settings. Patient comfort in student participation was greater for those seen by a female student and those who had previously had a student involved in their care or previously attended the hospital. CONCLUSION: Patient perceptions of students' involvement in their obstetrics and gynaecology care are mainly positive. Satisfaction levels differ with the gender of the student, the age of the patient, the location of care and for those for whom English is their first language. Attention must be paid to informing patients of the presence and possible level of interaction of students in their care. PMID- 21981309 TI - The effect of topography on differentiation fates of matrigel-coated mouse embryonic stem cells cultured on PLGA nanofibrous scaffolds. AB - Due to pluripotency of embryonic stem (ES) cells, these cells are an invaluable in vitro model that investigates the influence of different physical and chemical cues on differentiation/development pathway of specialized cells. We sought the effect of roughness and alignment, as topomorpholocial properties of scaffolds on differentiation of green fluorescent protein-expressing ES (GFP-ES) cells into three germ layers derivates simultaneously. Furthermore, the effect of Matrigel as a natural extracellular matrix in combination with poly(lactic-co-glycolic acid) (PLGA) nanofibrous scaffolds on differentiation of mouse ES cells has been investigated. The PLGA nanofibrous scaffolds with different height and distribution of roughness and alignments were fabricated. Then, the different cell differentiation fats of GFP-ES cells plated on PLGA and PLGA/Matrigel scaffolds were analyzed by gene expression profiling. The findings demonstrated that distinct ranges of roughness, height, and distribution can support/promote a specific cell differentiation fate on scaffolds. Coating of scaffolds with Matrigel has a synergistic effect in differentiation of mesoderm-derived cells and germ cells from ES cells, whereas it inhibits the derivation of endodermal cell lineages. It was concluded that the topomorpholocial cues such as roughness and alignment should be considered in addition to other scaffolds properties to design an efficient electrospun scaffold for specific tissue engineering. PMID- 21981311 TI - Application of response surface methodology in the optimisation of a growth medium for enhanced natural preservative bacteriocin production by a probiotic bacterium. AB - In this study, a statistics-based experimental design was utilised for the optimisation of a growth medium which possibly enhanced bacteriocin production by Streptococcus phocae PI80. Carbon, nitrogen sources and a bio-surfactant were first screened using a one variable at a time technique and scored for increasing yield production. The selected variables were further statistically optimised using response surface methodology with a central composite design. The high- and low-level limits of the selected variables were determined, and a set of 34 experimental runs were performed. The concentration of each medium ingredient influenced the bacteriocin activity to about 22,500 AU mL-1. The carbon and nitrogen sources were identified as significant factors in restraining the bacteriocin activity produced by S. phocae PI80. The statistics-based experimental design was found to be very efficient in optimising the media components in a number of experimental runs, with a three-fold increase in bacteriocin activity compared to the un-optimised medium. The optimum medium composition was found to be sodium succinate (10.0 g L-1), yeast extract (4.0 g L 1), glucose (9.0 g L-1), NaCl (10.0 g L-1), Tween 80 (6.0 g L-1) and K2HPO4 (1.0 g L-1). This optimised medium is two-fold more cost effective than the commercial Lactobacillus MRS medium. PMID- 21981310 TI - Increased dosage of tumor suppressors limits the tumorigenicity of iPS cells without affecting their pluripotency. AB - Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells represent a promising therapeutic tool for many diseases, including aged tissues and organs at high risk of failure. However, the intrinsic self-renewal and pluripotency of ES and iPS cells make them tumorigenic, and hence, the risk of tumor development hinders their clinical application. Here, we present a novel approach to limit their tumorigenicity and increase their safety through increased copy number of tumor suppressors. iPS containing an extra copy of the p53 or Ink4a/ARF locus show normal pluripotency, as determined by in vitro and in vivo differentiation assays. Yet, while retaining full pluripotency, they also possess an improved engagement of the p53 pathway during teratocarcinoma formation, which leads to a reduced tumorigenic potential in various in vitro and in vivo assays. Furthermore, they show an improved response to anticancer drugs, which could aid in their elimination in case tumors arise with no adverse effects on cell function or aging. Our system provides a model for studying tumor suppressor pathways during reprogramming, differentiation, and cell therapy applications. This offers an improved understanding of the pathways involved in tumor growth from engrafted pluripotent stem cells, which could facilitate the use of ES and iPS cells in regenerative medicine. PMID- 21981312 TI - Assessment of oxidative status and genotoxicity in photocopier operators: a pilot study. AB - Occupational exposure to photocopiers has been indicated as being responsible for a number of health complaints, particularly effects on the respiratory, immunological, and nervous systems. In this study, we investigated oxidative and genotoxic damage in photocopier operators by assessing catalase activity (CAT), reduced vs. oxidized glutathione ratio (GSH/GSSG), level of lipid peroxidation (TBARS), damage index by Comet assay (DICA), and buccal cells with micronuclei (BCMN). Our results reveal that the TBARS levels in operators were increased (27%; p<0.05) but that no significant alterations to GSH/GSSG or CAT activity were observed. The DICA and the number of BCMN were significantly increased (134% and 100%, respectively; p<0.05) in the exposed group. There was a significant association between the time in months spent at work and DNA damage in lymphocytes (r(s) = 0.720; p<0.001) and buccal cell with MN (r(s) = 0.538; p<0.001). Because laser printers and photocopiers have become increasingly used, it is important to control human exposure using reliable biomarkers. PMID- 21981313 TI - The number of benign moles excised for each malignant melanoma: the number needed to treat. AB - BACKGROUND: The ratio of benign moles excised for each malignant melanoma (MM) diagnosed, i.e. the number needed to treat (NNT), may be a useful indicator of diagnostic accuracy and the efficient use of healthcare resources, and may have personal implications for the patient. AIM: To assess the NNT for a group of consultant dermatologists serving a population of 600,000, and to compare this with similar studies from other countries. METHODS: This was a retrospective analysis of data on pigmented lesions excised over a 5-year period (2005-2009). The lesions were divided into three groups: benign naevi (BN), dysplastic naevi (DN) and MM. The NNT ratio was calculated as (BN + DN + MM)/MM. RESULTS: In total, 4691 lesions were examined. The overall mean NNT was 6.3, with a range of 4.9-11.3 for each of nine consultant dermatologists. The mean NNT was 7.6 for female and 4.8 for male patients. There were more patients with BN (n = 3534; 75%) than with DN (n = 407; 9%) or MM (n = 750; 16%). The gender representation was similar in the DN and MM groups, but had a disproportionately female bias in the BN group (67% female, 33% male patients). Overall, there were more female patients in all three groups [2962 female patients (63%) and 1729 male patients (37%)]. CONCLUSIONS: The NNT of 6.3 in this study compares favourably with NNT ratios from studies of dermatologists from other countries. This study may encourage other countries and individual doctors to assess their NNT ratios, as it may be an important indicator of the efficient use of resources and the avoidance of unnecessary surgery for patients. PMID- 21981315 TI - Artifacts of CD burning in the Microsoft Windows master file table. AB - When theft of a physical item occurs it is detectable by the fact that the object is missing, however, when the theft of a digital item occurs it can go unnoticed as exact replicas can be created. The original file is left intact but valuable information has been absconded. One of the challenges facing digital forensic examiners is detecting when files have been copied off of a computer system in some fashion. While certain methods do leave residual evidence behind, CD Burning has long been held as a copying method that cannot be identified. Through testing of the burning process and close examination of the New Technology File System (NTFS), artifacts from the master file table in the various versions of Microsoft Windows, markers have been found that are associated with copying or "burning" files to CD or DVD. Potential evidence that was once overlooked may now be detectable. PMID- 21981314 TI - Spontaneous conversion of first onset atrial fibrillation. AB - BACKGROUND/AIM: We studied all patients admitted to hospital with first onset atrial fibrillation (AF) to determine the probability of spontaneous conversion to sinus rhythm and to identify factors predictive of such a conversion. METHODS: We retrospectively reviewed charts of 438 consecutive patients admitted to hospital with first onset AF from 1 January 2006 to 31 December 2009. The patients were divided into two groups, recent onset AF defined as AF < 48 h or longer lasting AF, defined as AF > 48 h. RESULTS: Spontaneous conversion occurred in 54% (n = 203; 95% confidence interval: 49-59%). In the group with first onset AF < 48 h, spontaneous conversion occurred in 77%, compared with 36% in the group with first onset AF > 48 h. Logistic regression analysis identified duration of AF as a highly significant predictor of spontaneous conversion to sinus rhythm (odds ratio 5.9; 95% confidence interval: 4.0-8.6, P < 0.001). CONCLUSIONS: Spontaneous conversion occurred in 54%, increasing to 77% when AF had persisted less than 48 h. PMID- 21981317 TI - Involvement of mast cells in inflammation induced by Trichomonas vaginalis via crosstalk with vaginal epithelial cells. AB - Vaginal epithelial cells (VECs) are thought to function as immune-responsive cells in trichomoniasis, and mast cells have been detected in vaginal smears and the vaginal wall in trichomoniasis. It therefore seemed possible that the VEC trichomonad reaction might affect the activity of mast cells present in the lamina propria of the vaginal mucosa. In this study, we tested whether culture supernatants of VEC incubated with Trichomonas vaginalis (TCM) could stimulate mast cells. When VECs (MS74) were incubated with live trichomonads, IL-8, IL-6 and MCP-1 expressions increased in the TCM, and mast cells (HMC-1) and human neutrophils migrated more actively towards the TCM. Also, when the TCM was added to mast cells, beta-hexosaminidase and cytokines (IL-8 and TNF-alpha) expressions were increased. Moreover, the culture supernatant of mast cells incubated with TCM (M-TCM) had more increased chemotactic activity for neutrophils than that of TCM. We conclude that inflammatory mediators made by VECs in response to activation by T. vaginalis activate and attract mast cells and then stimulate them to induce neutrophil migration. Our results indicate, for the first time, that VECs play a role in the infiltration of mast cells and neutrophils early in T. vaginalis infection. PMID- 21981316 TI - Immunosuppressive effects of red blood cells on monocytes are related to both storage time and storage solution. AB - BACKGROUND: Reduced monocyte function is associated with adverse outcomes from critical illness. Red blood cells (RBCs) are thought to impair monocyte function but relationships between RBC storage solution and monocyte suppression are unknown. This study was designed to test the hypothesis that immunosuppressive effects of RBCs on monocytes are related to both storage time and preservative solution. STUDY DESIGN AND METHODS: Monocytes from healthy adult donors were co cultured with RBCs that had been stored in AS-1, AS-3, or CPD only for 7, 14, or 21 days. Cells were then stimulated with lipopolysaccharide (LPS) and their supernatants assayed for tumor necrosis factor (TNF)-alpha and interleukin (IL) 10. Transwell experiments were performed to evaluate the role of cell-to-cell contact. Monocyte mRNA expression was quantified by real-time-polymerase chain reaction. RESULTS: LPS-induced TNF-alpha production capacity was reduced compared to controls for all groups, but CPD-only RBCs suppressed monocyte function more than RBCs stored in AS-1 (p = 0.007) and AS-3 (p = 0.006). IL-10 production was preserved or augmented in all groups. A longer storage time was associated with reduced TNF-alpha production capacity for AS-1 and AS-3 groups but not CPD. Preventing cell-to-cell contact did not eliminate the inhibitory effect of RBCs on monocyte responsiveness. RBC exposure was associated with decreased LPS induced TNFA mRNA expression (p < 0.05 for all groups). CONCLUSIONS: CPD-only RBCs suppressed monocyte function more than RBCs stored with additive solutions. TNF-alpha production was reduced even in the absence of cell-to-cell contact and was impaired at the mRNA level. Further work is needed to understand the role of preservative solutions in this process. PMID- 21981318 TI - Measurement properties of the Motor Evaluation Scale for Upper Extremity in Stroke patients (MESUPES). AB - PURPOSE: To investigate inter-rater reliability of the Motor Evaluation Scale for Upper Extremity in Stroke patients (MESUPES), to provide estimates of the minimal detectable change (MDC) of the MESUPES and to investigate concurrent validity in relation to the arm scores of the Modified Motor Assessment Scale (M MAS). METHODS: Forty-two stroke patients (mean age 56 +/- 12 years) were independently assessed within a 48-hours window by two raters in different pairs (total available raters = 4). RESULTS: Weighted kappa analysis indicated good to very good agreement at item level (range 0.63-0.96). The relative and absolute reliability of the total score of MESUPES (maximum 58) was high according to the intraclass correlation coefficients (ICC = 0.98) and the standard error of measurement (SEM = 2.68). The MDC for three levels of confidence was calculated: A score change of 8, 7 and 5 is necessary for a MDC to have confidence of 95%, 90% and 80%, respectively, of a genuine change. Correlation between the MESUPES and M MAS was high (r(s) = 0.87). CONCLUSIONS: The MESUPES shows high inter-rater reliability, and our study provides useful estimates of MDC for different levels of certainty. Additional research to confirm concurrent validity and to examine other psychometric properties of the MESUPES such as sensitivity is needed. PMID- 21981319 TI - Short-term outcome after gluteus maximus myocutaneous flap reconstruction of the pelvic floor following extra-levator abdominoperineal excision of the rectum. AB - AIM: Extra-levator abdominoperineal excision (APE) of the rectum has been introduced with the aim of improving the oncological outcome of low rectal cancer. The procedure includes resection of the levator muscles en bloc with the mesorectum, leaving a larger perineal defect than after conventional APE. This study reports short-term outcome of gluteus maximus myocutaneous flap reconstruction on perineal wound healing. METHOD: Sixty-five patients were studied after extra-levator APE and a one-sided myocutaneous flap for a low or locally recurrent rectal cancer at the Karolinska University Hospital from January 2002 to December 2008. Fifty-nine had received neoadjuvant radio- or radiochemotherapy. All perineal complications occurring within 30 days after surgery were registered. In addition, the status of the perineal reconstruction at 6 months and 1 year after surgery was assessed based on medical records from outpatient visits. RESULTS: Twenty-seven (41.5%) patients had one or more perineal wound complications. A minor wound infection occurred in 15, while 12 had either a more severe infection with dehiscence or a pelvic abscess. The reconstruction was completely healed in 91% of the patients at 1 year. CONCLUSION: Although the vast majority of the perineal reconstructions were healed at 1 year, the short-term perineal wound complication rate of gluteus maximus flap reconstruction was high. PMID- 21981320 TI - Combined effects of prefermentative skin maceration and oxygen addition of must on color-related phenolics, volatile composition, and sensory characteristics of Airen white wine. AB - The effects of the joint prefermentative maceration and hyperoxygenation of Airen white must and wine on the phenolic content, chromatic characteristics, volatile composition, and sensory characteristics, not previously described in combination, have been evaluated. A total of 20 phenolic and 149 volatile compounds have been identified and quantified for that purpose. As a consequence of the oxygen addition, the concentrations of hydroxycinnamic acid derivatives and flavan-3-ols decreased (above all t-GRP and (+)-catechin), leading to color stabilization, but also the concentrations of several volatile compounds with a great importance for quality aroma decreased. Prefermentative skin maceration, previously applied to the hyperoxygenation of Airen musts, provided the aforementioned color stabilization in the respective wine but also increased the content of short-chain fatty acid esters and terpenes and decreased the concentration of C(6) alcohols. That combination of prefermentative treatments (skin maceration followed by must hyperoxygenation) produced an improvement of the global impression of the final wine based on significantly better scores of tropical fruit, body, and herbaceous notes. PMID- 21981321 TI - BMP2/7 heterodimer can modulate all cellular events of the in vitro RANKL mediated osteoclastogenesis, respectively, in different dose patterns. AB - Bone morphogenetic protein (BMP) heterodimers can trigger and sustain osteoblastic bone regeneration in significantly lower dosages than BMP homodimers. However, their effects on osteoclastic activity-a paramount coupling process with ostoblastic activity-remain undocumented. In this study, we delineated the functional characteristics of BMP2/7 heterodimer in inducing the in vitro osteoclastogenesis. We compared the dose-dependent effects of BMP2/7 heterodimer on the osteoclastogenesis of a preosteoclast cell line (RAW264.7) with those of BMP2 and BMP7 homodimers under the stimulation of 50 ng/mL receptor activator of nuclear factor-kappaB ligand. We quantitatively monitored the following parameters: cell proliferation, osteoclastic genes expression, morphological characteristics of osteoclasts, and calcium phosphate (CaP) resorption. BMP2/7 heterodimer could dose dependently modulate each osteoclastogenic event with different concentration patterns from the BMP homodimers. All BMPs of 10-150 ng/mL could increase the numbers of osteoclasts. Not BMP7 but 50-200 ng/mL BMP2 homodimer and 100-200 ng/mL BMP2/7 heterodimer could significantly enlarge the average surface-area of an osteoclast. BMP2/7 of 5-150 ng/mL could significantly enhance the osteoclastic CaP resorption to a similar level as the two homodimers. BMP2/7 heterodimer affects every osteoclastogenic event in a complicated dose-dependent manner. Low-concentration BMP2/7 heterodimer may favor a rapid and spontaneous remodeling of its induced bone and, thus, bear a promising potential in cytokine-based tissue engineering. PMID- 21981323 TI - Electrophoretic time-of-flight measurements of single DNA molecules with two stacked nanopores. AB - Electrophoretic transport through a solid-state nanodevice comprised of two stacked nanopore sensors is used to determine the free-solution mobility of DNA molecules based on their "time-of-flight" between the two pores. Mobility measurements are possible at very low (100 pM) DNA concentration and for low as well as high salt concentrations (here 30 mM and 1 M KCl). The mechanism of DNA transport through the device is elucidated by statistical analysis, showing the free-draining nature of the translocating DNA polymers and a barrier-dominated escape through the second pore. Furthermore, consecutive threading of single molecules through the two pores can be used to gain more detailed information on the dynamics of the molecules by correlation analysis, which also provides a direct electrical proof for translocation. PMID- 21981324 TI - Artistic productivity and creative thinking in Parkinson's disease. AB - BACKGROUND AND PURPOSE: Creative drive and enhanced artistic-like production may emerge in patients with Parkinson's disease (PD) during dopaminergic therapy. However, it has not been described to date whether this artistic-like production results from dopaminergic drugs triggering innate skills or it could be considered as a repeated behavior possibly associated with impulse control disorders (ICDs). METHODS: We investigated creative drive in a cohort of cognitively preserved patients with PD by means of the Torrance Test of Creative Thinking (TTCT). We also investigated a putative association between creative drive and ICDs in 36 PD patients with (PD-c) or without (PD-nc) increased artistic-like production and 36 healthy controls (HC). We considered artistic like productivity to be enhanced if patients reported working on any form of art more than 2h per day after the introduction of dopaminergic treatment. The TTCT, the Barratt Impulsiveness Scale (BIS-11A), the Minnesota Impulsive Disorders Interview (MIDI), and the Punding Rating Scale were applied. RESULTS: Mean TTCT score of PD-c was found to be similar to HC (169.4+/-51.6 vs. 170.2+/-69.7, respectively), and both PD-c and HC had significantly higher TTCT scores than patients with PD-nc (125.4+/-46.1 P<0.05). TTCT did not correlate with any demographic or clinical data in both PD subgroups. No correlation was found between TTCT, BIS-11A, and MIDI. CONCLUSIONS: Our study suggests that newly acquired artistic-like production in patients with PD is not associated with impulsivity or ICDs. Artistic-like production might represent the emerging of innate skills in a subset of predisposed patients with PD on dopaminergic therapy. PMID- 21981325 TI - The G protein coupled receptor Gpr153 shares common evolutionary origin with Gpr162 and is highly expressed in central regions including the thalamus, cerebellum and the arcuate nucleus. AB - The Rhodopsin family of G protein coupled receptors (GPCRs) includes the phylogenetic alpha-group consisting of about 100 human members. The alpha-group is the only group of GPCRs that has many receptors for biogenic amines which are major drug targets. Several members of this group are orphan receptors and their functions are elusive. In this study we present a detailed phylogenetic and anatomical characterization of the Gpr153 receptor and also attempt to study its functional role. We identified the homologue of Gpr153 in the elephant shark genome and phylogenetic and synteny analyses revealed that Gpr162 and Gpr153 share a common ancestor that split most likely through a duplication event before the divergence of the tetrapods and the teleost lineage. A quantitative real-time PCR study reveals widespread expression of Gpr153 in the central nervous system and all the peripheral tissues investigated. Detailed in situ hybridization on mouse brain showed specifically high expression in the thalamus, cerebellum and the arcuate nucleus. The antisense oligodeoxynucleotide knockdown of Gpr153 caused a slight reduction in food intake and the elevated plus maze test showed significant reduction in the percentage of time spent in the centre square, which points towards a probable role in decision making. This report provides the first detailed characterization of the evolution, expression and primary functional properties of the Gpr153 gene. PMID- 21981326 TI - A bipolar radiofrequency, infrared, vacuum and mechanical massage device for treatment of cellulite: a pilot study. AB - Cellulite has a complex and multifactorial etiology. Synergistic action on treating cellulite has gained support in the treatment of cellulite. This study evaluated safety and efficacy of a bipolar radiofrequency, infrared, vacuum and mechanical massage device for cellulite treatment and reduction of body measures. This was a pilot study, which assessed 9 subjects who presented body mass index from 18 to 25 Kg/Kg and at least grade 6 in the Cellulite Severity Scale (CSS). All subjects underwent a 12-session treatment of posterior thighs and buttocks. There was a significant reduction of the hip circumference (p = 0.001), however, no changes in thigh circumferences were observed (p = 0.4). CSS has improved specifically on both buttocks [p = 0.002 (left side) and p = 0.038 (right side)], and no changes were observed on thighs. The studied device demonstrated efficacy in the reduction of cellulite severity and body circumference measures in the buttocks. PMID- 21981331 TI - Are patients 1 year post-stroke active enough to improve their physical health? AB - PURPOSE: This study aimed to quantify physical activity one year post-stroke--by means of a multifaceted approach combining absolute, relative, and self-reported measures of physical activity (PA)--and to investigate their mutual associations. The determinants of PA were explored. METHOD: Daily PA was measured in 16 mildly disabled stroke patients (median RMA-GF score of 12 (IQR = 10-12.5)) using a heart rate monitor, a pedometer, the Baecke Physical Activity Questionnaire and the Physical Activity Scale for individuals with physical disabilities. Potential determinants were age, gender, functional mobility, peak exercise capacity, mood, participation and hours of daylight. RESULTS: On average, stroke participants had a good baseline level of activity (44 +/- 39 min/day spent moderate active, 6428 +/- 4117 steps/day), but only three (19%) performed more than 10,000 steps/day, required for health benefits. Functional mobility, cardiorespiratory fitness, mood and participation were related to the total daily steps, but not to the time spent in moderate intense activities. Discrepancies between absolute (frequency and duration) and relative (intensity) measures of PA exist regarding the achieved quantity and its potential determinants. CONCLUSIONS: It is not only important to be active, but to be active enough to improve health. Health recommendation for stroke survivors to perform moderate intense PA needs to be translated into a pedometer-based step goal. PMID- 21981330 TI - Bioresponsive mesoporous silica nanoparticles for triggered drug release. AB - Mesoporous silica nanoparticles (MSNPs) have garnered a great deal of attention as potential carriers for therapeutic payloads. However, achieving triggered drug release from MSNPs in vivo has been challenging. Here, we describe the synthesis of stimulus-responsive polymer-coated MSNPs and the loading of therapeutics into both the core and shell domains. We characterize MSNP drug-eluting properties in vitro and demonstrate that the polymer-coated MSNPs release doxorubicin in response to proteases present at a tumor site in vivo, resulting in cellular apoptosis. These results demonstrate the utility of polymer-coated nanoparticles in specifically delivering an antitumor payload. PMID- 21981337 TI - Atraumatic bilateral femoral neck fractures during pregnancy: a missed diagnosis. PMID- 21981332 TI - A systematic review of interventions for reducing pain and distress in children undergoing voiding cystourethrography. AB - Voiding cystourethrography (VCUG) is commonly performed to screen for vesicoureteric reflux or other urological anomalies but has a potential to provoke distress in infants and children. We performed a systematic review of randomized controlled trials of interventions to reduce distress, pain or anxiety during VCUG. Eight trials (591 participants) met the inclusion criteria. CONCLUSION: Conscious sedation with midazolam effectively alleviates the distress of VCUG in children older than 1 year of age. Psychological preparation and warmed contrast medium may also be effective. Nitrous oxide 50% may be an alternative to midazolam, but further evidence is needed. PMID- 21981322 TI - Adaptive evolution of a key gene affecting queen and worker traits in the honey bee, Apis mellifera. AB - The vitellogenin egg yolk precursor protein represents a well-studied case of social pleiotropy in the model organism Apis mellifera. Vitellogenin is associated with fecundity in queens and plays a major role in controlling division of labour in workers, thereby affecting both individual and colony-level fitness. We studied the molecular evolution of vitellogenin and seven other genes sequenced in a large population panel of Apis mellifera and several closely related species to investigate the role of social pleiotropy on adaptive protein evolution. We found a significant excess of nonsynonymous fixed differences between A. mellifera, A. cerana and A. florea relative to synonymous sites indicating high rates of adaptive evolution at vitellogenin. Indeed, 88% of amino acid changes were fixed by selection in some portions of the gene. Further, vitellogenin exhibited hallmark signatures of selective sweeps in A. mellifera, including a significant skew in the allele frequency spectrum, extreme levels of genetic differentiation and linkage disequilibrium. Finally, replacement polymorphisms in vitellogenin were significantly enriched in parts of the protein involved in binding lipid, establishing a link between the gene's structure, function and effects on fitness. Our case study provides unequivocal evidence of historical and ongoing bouts of adaptive evolution acting on a key socially pleiotropic gene in the honey bee. PMID- 21981338 TI - In situ infrared molecular detection using palladium-containing zeolite films. AB - In situ IR detection of carbon monoxide in the presence of hydrocarbons (methanol and pentane) using Pd-containing zeolite thin films is reported. The thin films are prepared by spin coating deposition of nanosized LTL and BEA type zeolites suspensions; the palladium clusters are introduced in the nanosized zeolites by ion exchange followed by gamma radiolysis of the coating suspensions. The Pd containing zeolite films with a thickness of 200 nm are exposed to a single gas (either CO or hydrocarbons) or gas mixtures in the presence of water (100 ppm), and the IR spectra are collected continuously at 25, 75, and 100 degrees C. The fast recognition of very low concentrations of CO (2-100 ppm) in the presence of highly concentrated vapors of methanol or pentane (400-4000 ppm) with the Pd containing zeolite films is demonstrated. The detection of CO and hydrocarbons is instant, which is a function of the low thickness of the films, small size of the individual zeolite crystals, and regular size and high stability of the Pd clusters in the zeolite films. The heat of adsorption for all experiments is similar (15 kJ.mol(-1)), which is explained with weak interactions between the carbon monoxide and palladium clusters in the zeolite films at temperatures below 100 degrees C. The nanosized zeolites with homogeneously distributed Pd clusters deposited in thin films demonstrate high molecular recognition capacity toward low concentrations of carbon monoxide under real environmental conditions, i.e., in the presence of water and hydrocarbons. PMID- 21981339 TI - Animal-related fatalities--part I: characteristic autopsy findings and variable causes of death associated with blunt and sharp trauma. AB - Animals may be responsible for an array of potentially lethal injuries. Blunt force injuries characteristically involve larger animals such as cattle or horses that may kick, crush, or trample a victim causing head and facial injuries. Farm workers in particular are at high risk of lethal injuries involving the head and torso. Significant blunt trauma may be found in vehicle occupants after collisions with large animals such as camels or moose. Rarely, zookeepers may be crushed by particularly massive animals such as elephants. Sharp force injuries usually involve carnivore bites, most often from dogs with a "hole and tear" pattern of wounding. Injuries from animals such as alligators and sharks may have a significant component of crushing. Incised wounds may result in death from exsanguination and air embolism. On occasion, blunt or sharp trauma from animal activity may be confused with postmortem damage or with inflicted injury from an assault. PMID- 21981340 TI - Involvement of the bulge region with decreased expression of hair follicle stem cell markers in senile female cases of alopecia areata. AB - BACKGROUND: Alopecia areata (AA) is a common hair loss disorder characterized by cellular autoimmune reaction predominantly involving the bulbar portion of anagen hair follicles. In most cases of AA, the bulge stem cell area remains intact. Recently, a couple of molecules, such as keratin15 (K15) and CD200, have been identified as biomarkers of human bulge cells. Of note, an immunosuppressive molecule, CD200 is speculated to provide an immune privilege for bulge stem cells. OBJECTIVE: To investigate expression levels of stem cell markers, especially CD200, in two senile female cases of AA with unusual lymphocytic cell infiltrates surrounding both the bulge and the bulbar regions. Then, compare them with those in common AA cases without the bulge involvement. METHODS: Transverse sections containing the bulge levels were prepared from unaffected and affected lesions, respectively, from each AA group and immunohistochemical investigation using anti-K15 and CD200 antibodies was performed. Importantly, an approach to detect CD200 in paraffin sections was newly developed. Immunoreactivities of individual antibodies were compared between corresponding lesions in each patient group. RESULTS: In unaffected bulge lesions, K15 immunoreactivity was not different between bulge-involving AA and common AA groups, whilst that of CD200 was decreased in the former group. Both K15 and CD200 immunoreactivities were decreased in affected bulge lesions of bulge-involving AA compared to the bulge of common AA cases. CONCLUSION: Selective downregulation of CD200 in the bulge area could contribute to the collapse of immune privilege with resultant unusual bulge involvement in a subset of AA. PMID- 21981341 TI - Unilateral nevoid telangiectasia accompanied by neurological disorders. AB - BACKGROUND: Unilateral nevoid telangiectasia (UNT) is a unique vascular dermatosis of ambiguous aetiology. OBJECTIVE: To investigate the role of neurological disorder in pathogenesis of the UNT. METHODS: We investigated eight consecutive patients with unilateral nevoid telangiectasia. Detailed dermatological and neurological examinations, and magnetic resonance imaging were performed on each patient. In case of presence of dysesthesia over the skin lesion, electroneuromyography was performed to determine any relationships between lesions and peripheral neuropathy. RESULTS: All the patients had hypoesthesia over the skin lesion. The cranial magnetic resonance imaging showed subcortical hamartomatous lesions in one patient and demyelinized plaques on the corpus of the caudate nucleus and the pontin area in another. Electroneuromyography evaluation was nonspecific. CONCLUSION: In our study, neurological disorders were associated with UNT. Thus, it can be speculated that neurological disorders might contribute to the development and/or progression of UNT. Patients with UNT should be encouraged for neurological investigation. PMID- 21981342 TI - The Tzanck smear: an auspicable return to the past. PMID- 21981343 TI - Fluorescent dyes and their supramolecular host/guest complexes with macrocycles in aqueous solution. PMID- 21981344 TI - Theoretical design and analysis of multivolume digital assays with wide dynamic range validated experimentally with microfluidic digital PCR. AB - This paper presents a protocol using theoretical methods and free software to design and analyze multivolume digital PCR (MV digital PCR) devices; the theory and software are also applicable to design and analysis of dilution series in digital PCR. MV digital PCR minimizes the total number of wells required for "digital" (single molecule) measurements while maintaining high dynamic range and high resolution. In some examples, multivolume designs with fewer than 200 total wells are predicted to provide dynamic range with 5-fold resolution similar to that of single-volume designs requiring 12,000 wells. Mathematical techniques were utilized and expanded to maximize the information obtained from each experiment and to quantify performance of devices and were experimentally validated using the SlipChip platform. MV digital PCR was demonstrated to perform reliably, and results from wells of different volumes agreed with one another. No artifacts due to different surface-to-volume ratios were observed, and single molecule amplification in volumes ranging from 1 to 125 nL was self-consistent. The device presented here was designed to meet the testing requirements for measuring clinically relevant levels of HIV viral load at the point-of-care (in plasma, <500 molecules/mL to >1,000,000 molecules/mL), and the predicted resolution and dynamic range was experimentally validated using a control sequence of DNA. This approach simplifies digital PCR experiments, saves space, and thus enables multiplexing using separate areas for each sample on one chip, and facilitates the development of new high-performance diagnostic tools for resource-limited applications. The theory and software presented here are general and are applicable to designing and analyzing other digital analytical platforms including digital immunoassays and digital bacterial analysis. It is not limited to SlipChip and could also be useful for the design of systems on platforms including valve-based and droplet-based platforms. In a separate publication by Shen et al. (J. Am. Chem. Soc., 2011, DOI: 10.1021/ja2060116), this approach is used to design and test digital RT-PCR devices for quantifying RNA. PMID- 21981345 TI - Social, structural and behavioral drivers of concurrent partnerships among African American men in Philadelphia. AB - African Americans face disproportionately higher risks of HIV infection. Concurrent sexual relationships, or sexual partnerships that overlap in time, are more common among African Americans than individuals of other races and may contribute to racial disparities in HIV infection. However, little is known about attitudes, norms and practices among individuals engaged in concurrent partnerships. Little is also known about the processes through which structural, behavioral, and social factors influence concurrent sexual relationships. We recruited 24 heterosexual African American men involved in concurrent sexual relationships from a public health clinic in Philadelphia. We conducted in-depth interviews exploring these men's sexual practices; social norms and individual attitudes about concurrency; perceived sexual health risks with main and non-main partners; and the social, structural, and behavioral factors contributing to concurrent sexual relationships. Twenty-two men reported having one main and one or more non-main partners; two reported having no main partners. Respondents generally perceived sexual relationships with non-main partners as riskier than relationships with main partners and used condoms far less frequently with main than non-main partners. Most participants commented that it is acceptable and often expected for men and women to engage in concurrent sexual relationships. Social factors influencing participants' concurrent partnerships included being unmarried and trusting neither main nor non-main partners. Structural factors influencing concurrent partnerships included economic dependence on one or more women, incarceration, unstable housing, and unemployment. Several men commented that individual behavioral factors such as alcohol and cocaine use contributed to their concurrent sexual partnerships. Future research and interventions related to sexual concurrency should address social and structural factors in addition to conventional HIV risk-taking behaviors. PMID- 21981347 TI - Negative screening colonoscopy after a positive guaiac faecal occult blood test: not a contraindication to continued screening. AB - AIM: In guaiac faecal occult blood test (gFOBT) screening at least 50% of positive individuals will have a colonoscopy negative for colorectal neoplasia. The question of continuing screening in this group has not been addressed. METHOD: Data on participants aged 50-69 years with a positive gFOBT result and a negative colonoscopy were followed through the biennial screening pilot conducted between 2000 and 2007 in Scotland. RESULTS: In the first screening round, 1527 colonoscopies were negative for neoplasia. 1300 were re-invited in the second round, 905 accepted, and 157 had a positive gFOBT result, giving a positivity rate of 17.4%. Colonoscopy revealed 20 subjects with adenoma and six with invasive cancer. In the third screening round 1031 were invited for a third time and 730 accepted: 55 had a positive gFOBT test, giving a positivity rate of 7.5%. In this group, six colonoscopies revealed adenomas but there were no cancers diagnosed. In the third screening round, 108 individuals had had two positive gFOBT results and two subsequent negative colonoscopies. Eighty-four were invited for a third gFOBT, 66 accepted and 19 (25.6%) had a positive result none of whom had an adenoma or carcinoma. CONCLUSION: These data indicate that a negative colonoscopy following a positive gFOBT is not a contraindication for further screening, although this is likely to have a low yield of neoplastic pathology after two negative colonoscopies. PMID- 21981346 TI - Effects of prazosin, an alpha1-adrenergic receptor antagonist, on the seeking and intake of alcohol and sucrose in alcohol-preferring (P) rats. AB - BACKGROUND: Previous studies show that prazosin, an alpha(1) -adrenergic receptor antagonist, decreases alcohol drinking in animal models of alcohol use and dependence [Rasmussen et al. (2009) Alcohol Clin Exp Res 3:264-272; Walker et al. (2008) Alcohol 42:91-97] and in alcohol-dependent men [Simpson et al. (2009) Alcohol Clin Exp Res 33:255-263]. This study extended these findings by using a paradigm that allows for separate assessment of prazosin on motivation to seek versus consume alcohol or sucrose in selectively bred rats. METHODS: Alcohol preferring (P) rats were trained to complete an operant response that resulted in access to either 2% sucrose or 10% alcohol. A 4-week Seeking Test Phase examined responding in single, weekly extinction sessions when no reinforcer could be obtained. A 4-week Drinking Test Phase consisted of rats lever-pressing to "pay" a specified amount up front to gain access to unlimited alcohol (or sucrose) for a 20-minute period. On Seeking and Drinking test days, prazosin (0.0, 0.5, 1.0, and 1.5 mg/kg) was administered intraperitoneally 30 minutes prior to behavioral sessions. RESULTS: Rats were self-administering an average of 0.9 (+/-0.09) g/kg alcohol on vehicle test day and had pharmacologically relevant blood ethanol concentrations. Prazosin significantly decreased alcohol seeking at all doses tested. The highest dose of prazosin also increased the latency to first response for alcohol and decreased alcohol intake. While sucrose-seeking and intake were similarly affected by prazosin, the high dose of prazosin did not increase response latency. CONCLUSIONS: These findings are consistent with and extend previous research and suggest that prazosin decreases motivation to initiate and engage in alcohol consumption. The specificity of prazosin in attenuating the initiation of alcohol- but not sucrose-seeking suggests that this effect is not because of prazosin-induced motor-impairment or malaise. Together with previous findings, these data suggest that prazosin may be an effective pharmacotherapy, with specific application in people that drink excessively or have a genetic predisposition to alcohol abuse. PMID- 21981348 TI - The relationship between DNA methylation and telomere length in dyskeratosis congenita. AB - The regulation of telomere length (TL) is a complex process, requiring the telomerase enzyme complex and numerous regulatory proteins. Epigenetic regulation may also be important in telomere maintenance. Specifically, methylation at subtelomeres is associated with changes in TL in vitro and in mouse models. Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome characterized by exceedingly short telomeres and mutations in telomere biology genes. To understand the interaction between methylation and TL in humans, we measured LINE-1, pericentromeric (NBL2), and subtelomeric (D4Z4) methylation in peripheral blood DNA derived from 40 patients with DC and 51 mutation-negative relatives. Pearson's correlation coefficient and linear regression models were used to evaluate the relationship between age-standardized lymphocyte TL measured by flow FISH and % DNA methylation. No differences in % subtelomeric, LINE-1, or pericentromeric methylation between patients with DC and relatives were noted except for an increase in % subtelomeric methylation in DC patients with a telomerase-complex mutation (TERC, TERT, DKC1, or TCAB1) (63.0% in DC vs. 61.8% in relatives, P = 0.03). Positive correlations between TL and DNA methylation at LINE-1 (r = 0.39, P = 0.01) and subtelomeric (r = 0.32, P = 0.05) sites were present in patients with DC. The positive correlation between TL and % LINE-1 methylation was restricted to TINF2 mutations. In contrast, statistically nonsignificant inverse correlations between TL and % LINE-1 (r = -0.17), subtelomeric (r = -0.20) were present in unaffected relatives. This study suggests an interaction between TL and both subtelomeric and LINE-1 methylation, which may be altered based on mutation status of telomere biology genes. PMID- 21981350 TI - Influence of supersaturation and spontaneous catalyst formation on the growth of PbS wires: toward a unified understanding of growth modes. AB - High quality stoichiometric lead sulfide (PbS) wires were synthesized by a simple chemical vapor deposition (CVD) process using pure PbS powder as the material source. Growth mechanisms were systematically investigated under various growth conditions, with three modes of growth identified: direct vapor-liquid-solid (VLS) wire growth nucleating from the substrate surface, bulk PbS crystallites by vapor-solid (VS) deposition, and subsequent VLS growth nucleating on top of the bulk deposition through spontaneously formed catalyst particles. Furthermore, we found that these growth modes can be organized in terms of different levels of supersaturation, with VS bulk deposition dominating at high supersaturation and VLS wire growth on the substrate dominating at low supersaturation. At intermediate supersaturation, the bulk VS deposition can form larger crystallites with domains of similarly oriented wires extending from the flat facets. Both predeposited catalysts and spontaneously formed Pb particles were observed as nucleation catalysts, and their interplay leads to various interesting growth scenarios such as reversely tapered growth with increasing diameter. The VLS growth mechanism was confirmed by the presence of Pb-rich caps revealed in an elaborate cross-sectional transmission electron microscopy (TEM) experiment after focused ion beam milling in a modified lift-out procedure. Temperature-dependent photoluminescence (PL) of PbS wires was performed in the mid-infrared wavelength range for the first time, demonstrating strong light emission from band edge, blue-shifted with increasing temperature. The high optical quality of PbS wires may lead to important applications in mid-infrared photonics. The substrate growth temperature as low as 400 degrees C allows for silicon-compatible processing for integrated optoelectronics applications. PMID- 21981349 TI - Antinociceptive and anti-inflammatory activities of the essential oil of Nepeta crispa Willd. in experimental rat models. AB - This study was conducted to evaluate the antinociceptive and anti-inflammatory activities of the essential oil of Nepeta crispa. The study was done using the tail-flick and formalin test pain models and the paw oedema model of inflammation. Male Wistar rats were used as the animal model. The essential oil dose-dependently produced analgesia in the acute pain models, including the tail flick (p < 0.001) and the first phase of the formalin test (p < 0.01). In the late phase of the formalin test, as a model of chronic pain, the essential oil significantly reduced the pain-induced behaviour (p < 0.01). Nepeta crispa essential oil caused potent anti-inflammatory effects in the formalin-induced paw inflammation model and significantly reduced the paw oedema in all applied doses (p < 0.01). Its effects on pain in both the acute and chronic pain models and its anti-inflammatory effect suggest both central and peripheral mechanisms of action for the essential oil obtained from N. crispa. PMID- 21981351 TI - Preemptive use of plerixafor in difficult-to-mobilize patients: an emerging concept. AB - Mobilized peripheral blood (PB) is the preferred source of stem cells (PBSCs) for autologous stem cell transplantation (ASCT). The use of cytokines, alone or in combination with chemotherapy (chemomobilization), is currently the most common strategy applied to collect PBSCs. However, a significant proportion of patients with lymphoid malignancies fail to mobilize enough PBSCs to proceed to ASCT. Plerixafor has been recently introduced for clinical use to enhance PBSC mobilization and has been shown to be more effective than granulocyte-colony stimulating factor (G-CSF) alone in patients with multiple myeloma or non Hodgkin's lymphoma. There is limited experience on combining plerixafor with chemotherapy plus G-CSF in patients who mobilize poorly. This review attempts to summarize the published experience on the preemptive use of plerixafor after chemomobilization or G-CSF mobilization to enhance stem cell collection and to prevent mobilization failure. Current evidence suggests that addition of plerixafor is safe and effective in the large majority of the patients with low blood CD34+ cell counts after mobilization and/or poor yield after the first collection(s). Circulating CD34+ cell counts can be increased by severalfold with plerixafor and the majority of the patients considered difficult to mobilize can be successfully collected. Although more studies are needed to evaluate proper patient selection and optimal timing for the addition of plerixafor after chemotherapy, its mechanism of action inducing the rapid release of CD34+ cells from the marrow to the PB makes this molecule suitable for its "preemptive" use in patients who are difficult to mobilize. PMID- 21981352 TI - Beneficial effect of acitretin in Chanarin-Dorfman syndrome. AB - Chanarin-Dorfman syndrome (CDS) is an autosomal recessive metabolic disorder characterized by congenital ichthyosis and visceral complications due to accumulation of neutral lipids. CDS is caused by mutations in the ABHD5 (previously termed CGI-58) gene. In the present study, we assessed a young child presenting with ichthyosis and hepatomegaly, suggesting a diagnosis of CDS. We identified an intronic mutation, c.960 + 5G>A, which was found to result in skipping of exon 6. Abnormal results on liver function tests led us to treat the child with acitretin, which resulted in satisfactory clinical and laboratory responses. The present case illustrates the beneficial effect of acitretin treatment in CDS even in the presence of compromised liver function. PMID- 21981353 TI - Oral drug challenges in non-steroidal anti-inflammatory drug-induced urticaria, angioedema and anaphylaxis. AB - BACKGROUND: Urticaria, angioedema and anaphylaxis are common adverse reactions to non-steroidal anti-inflammatory drugs (NSAIDs). AIM: To investigate the clinical characteristics of NSAID-induced acute hypersensitivity reactions with structured oral drug challenges. METHODS: Patients with NSAID-induced urticaria, angioedema or anaphylaxis were challenged with either the homologous NSAID to confirm diagnosis or a heterologous NSAID to investigate cross-reactivity. Data were analysed retrospectively and supplemented by a telephone questionnaire. RESULTS: Sixty-eight patients (mean age 48.3, 53 females) reported a total of 75 instances of NSAID-induced reactions of which 64% were purely cutaneous and 36% were systemic anaphylaxis. Ibuprofen was the most frequent cause of reactions (35%), however, diclofenac was the most frequent cause of anaphylaxis (48%). Seventeen out of 40 (43%) homologous NSAID challenges were positive; presentation with anaphylaxis or reaction to diclofenac predicted a positive challenge. Only 7 of 28 (25%) of heterologous NSAID challenges were positive. Structured challenges enabled us to identify 23 (34%) patients with selective reactivity to a single NSAID, 19 (28%) patients with cross-reactivity to multiple NSAIDs and 23 (34%) patients in whom NSAID hypersensitivity was not reproduced. Selective reactors presented most often with anaphylaxis and some had a background of beta-lactam antibiotic allergy. Cross-reactive patients often had a background of chronic urticaria and presented with milder reactions. CONCLUSION: In the absence of a reliable in vitro test, structured drug challenges allow identification of selective and cross-reactive NSAID hypersensitivity syndromes. NSAID-induced anaphylaxis is often associated with selective hypersensitivity and patients may not need to avoid other NSAIDs. PMID- 21981355 TI - Clinical histories and molecular characterization of two afibrinogenemic patients: insights into clinical management. PMID- 21981356 TI - Novel application of human periodontal ligament stem cells and water-soluble chitin for collagen tissue regeneration: in vitro and in vivo investigations. AB - Human periodontal ligament stem cells (hPDLSCs) have been proposed as an alternative to conventional cosmetic fillers because they display an innate ability to synthesize collagen. The aims of this study were to determine the effects of water-soluble chitin (WSC) on the proliferation and migration of hPDLSCs, and to quantify collagen synthesis in vitro and in vivo compared with human adipose-derived stem cell (hADSC)s. hPDLSCs were isolated from healthy extracted teeth, and the cell proliferation and cell migration capacities of untreated hPDLSCs (control group) and WSC-treated hPDLSCs (test group) were compared. Insoluble/soluble collagen synthesis were also assessed, and collagen related markers were evaluated including lysyl oxidase (LOX), lysyl oxidase like (LOXL)1, LOXL2, and hydroxyproline. In vivo collagen formation was examined by transplanting hyaluronic acid as a cell carrier into the subcutaneous pockets of immunocompromised mice in the control and test groups; histology and immunohistochemistry analyses were performed 4 (n=4) and 8 (n=4) weeks later. There was a dose-dependent enhancement of hPDLSCs proliferation in the test group, and a concomitant reduction in cell migration. The amount of insoluble collagen formed was greater in the test group than in the control group (p<0.05), whereas soluble collagen formation was significantly reduced in the test group (p<0.05). The histology and immunohistochemistry results revealed that the amount of collagen formed in vivo was greater in WSC-treated hPDLSCs than in the control cells at 4 and 8 weeks (p<0.05), and histometric analysis at 8 weeks revealed that enhancement of collagen formation by hPDLSCs was greater than by hADSCs. These results indicate that WSC modulates the properties of hPDLSCs, rendering them more suitable for cosmetic soft-tissue augmentation. PMID- 21981354 TI - Phylogeography and bindin evolution in Arbacia, a sea urchin genus with an unusual distribution. AB - Among shallow water sea urchin genera, Arbacia is the only genus that contains species found in both high and low latitudes. In order to determine the geographical origin of the genus and its history of speciation events, we constructed phylogenies based on cytochrome oxidase I and sperm bindin from all its species. Both the mitochondrial and the nuclear gene genealogies show that Arbacia originated in the temperate zone of the Southern Hemisphere and gave rise to three species in the eastern Pacific, which were then isolated from the Atlantic by the Isthmus of Panama. The mid-Atlantic barrier separated two additional species. The bindin data suggest that selection against hybridization is not important in the evolution of this molecule in this genus. Metz et al. in a previous publication found no evidence of selection on bindin of Arbacia and suggested that this might be due to allopatry between species, which obviated the need for species recognition. This suggestion formed the basis of the conclusion, widely spread in the literature, that the source of selection on sea urchin bindin (where it does occur) was reinforcement. However, the range of Arbacia spatuligera overlaps with that of two other species of Arbacia, and our data show that it is hybridizing with one of them. We found that even in the species that overlap geographically, there are no deviations from selective neutrality in the evolution of bindin. PMID- 21981360 TI - Evaluation of 532-nm KTP laser treatment efficacy on acne vulgaris with once and twice weekly applications. AB - BACKGROUND: Light-based therapies and lasers have been proposed for the treatment of acne vulgaris but the efficacy and application periods of 532-nm KTP laser treatment are not clear. OBJECTIVE: To evaluate the efficacy and safety of 532-nm KTP laser and compare the effects of once and twice weekly applications in the treatment of mild to moderate acne vulgaris. METHODS: Totally 38 patients were treated once weekly and twice weekly in group I and in group II respectively. One half of the face of each patient was treated with 532-nm KTP and the other half was remained as untreated. Patients were evaluated at the beginning, one and four weeks after the last treatment session with Michaelsson acne severity grading score (MASS). RESULTS: Statistically significant improvement was found at second control (p = 0.005) in group I, and at the first (p = 0.004), and second (p < 0.001) controls in group II for treated sides. For both groups, changes of MASS were insignificant for untreated sites. Improvement of MASS of treated sides was not statistically significant between two treatment groups for both controls. CONCLUSION: 532-nm KTP laser treatment may be an alternative method in selected acne vulgaris patients. No significant difference was noted between once and twice weekly applications. PMID- 21981361 TI - Catalytic asymmetric synthesis of (+)-anthecotulide using enyne and Meyer Schuster rearrangements. AB - The bioactive sesquiterpene lactone (+)-anthecotulide (1) is synthesized for the first time, in a six-step sequence devoid of protecting groups. The key transformations are a novel Rh(I)-catalyzed asymmetric enyne rearrangement of a terminal alkynyl ester (4), to form the alpha-methylene-gamma-butyrolactone core, and a final-step mild Au(I)-catalyzed Meyer-Schuster rearrangement. PMID- 21981362 TI - Application of optical coherence tomography in glaucoma suspect eyes. AB - PURPOSE: The aim of the study was to compare the optical coherence tomography (OCT) parameters of the optic nerve head (ONH) and retinal nerve fibre layer (RNFL) and to identify which measurements are best able to differentiate between normal and glaucoma suspect eyes. METHODS: The study included 27 eyes with ocular hypertension (OHT), 33 eyes with pre-perimetric glaucoma (PG), 30 perimetrically unaffected eyes of patients with glaucoma in the fellow eye (FE) and 58 eyes of age-matched normal volunteers. All subjects underwent a complete eye examination with standard automated perimetry, optic disc photography and OCT imaging. Peripapillary 'fast RNFL thickness scans' and 'fast optic disc scans' were performed with time-domain OCT. The ONH and RNFL parameters were compared among the four study groups. The ONH and RNFL parameters were examined alone and then combined via four linear discriminant functions (LDF): LDF 1, the optimal combination of ONH parameters; LDF 2, the optimal combination of RNFL parameters; LDF 3, the optimal combination of both ONH and RNFL parameters; and LDF 4, the optimal combination of the best 11 parameters. The areas under the receiver operating curves (AUC) and the sensitivity at fixed specificity of at least 80 and 95 per cent were calculated for single parameters and LDF combinations and then compared. The best 11 parameters were selected based on their AUC values. RESULTS: Comparative analysis of OCT parameters revealed statistically significant differences in all seven ONH parameters in both PG and FE groups (and only in one ONH measurement in the ocular hypertensive group) when compared with normal eyes. Most of the RNFL parameters demonstrated statistically significant differences in all of the study groups when compared with the control group. The max-min parameter (0.835), inferior quadrant (0.833) and average RNFL thickness (0.829) obtained the highest AUC values in the whole glaucoma suspect group. The rim area had the best diagnostic accuracy among the ONH parameters (AUC = 0.817). The AUC values of the four LDF were: 0.825 (LDF 1), 0.882 (LDF 2), 0.902 (LDF 3) and 0.888 (LDF 4). Statistically significant differences were found between the AUC values of the single best ONH and RNFL parameters and LDF 3 and LDF 4. CONCLUSIONS: In the present study, RNFL parameters presented with better discriminatory abilities than ONH parameters in the OHT and FE groups. The ONH parameters demonstrated better diagnostic precision in differentiating between PG and normal eyes. The average RNFL thickness, max-min parameter and inferior quadrant RNFL thickness had the best abilities among single OCT measurements for discriminating between glaucoma suspect (including all ocular hypertensive, PG and FE eyes) and normal eyes. The combination of RNFL parameters only or both ONH and RNFL parameters, using linear discriminant analysis, provided the best classification results, improving the diagnostic accuracy of the instrument. PMID- 21981363 TI - Professionals' views of children's everyday life situations and the relation to participation. AB - PURPOSE: The aim was to determine professionals' views of everyday life situations (ELS) of importance for children and to explore how ELS correlate with the construct "Participation". This study was part of a larger work to develop a structured tool with code sets to identify child participation and support children with disabilities to describe what matters most for them in intervention planning. METHOD: The study had a concurrent mixed methods design. Information from one open-ended question and questionnaires were linked to the ICF-CY component Activities and Participation. Two concurrent data sets were compared. RESULTS: Proposed ELS were distributed across ICF-CY categories from low to high level of complexity and context specificity. The correlation with participation became stronger for the later chapters of the component (d7-d9). Differences between respondents due to working field, country, and children's ages were explored. Acts and tasks seemed most important for the youngest children, whereas ELS shifted towards societal involvement for adolescents. CONCLUSION: Eleven categories related to ICF-CY chapters d3-d9 emerged as ELS. Two age groups (infants/preschoolers and adolescents) are required to develop code sets for the new tool. The results need triangulation with other concurrent studies to provide corroborating evidence and add a family perspective. PMID- 21981364 TI - Carbon radical generation by d0 tantalum complexes with alpha-diimine ligands through ligand-centered redox processes. AB - High-valent tantalum complexes having redox-active alpha-diimine ligands, (alpha diimine)TaCl(n) (n = 3, 4), are prepared by the reaction of TaCl(5), alpha diimine ligands, and an organosilicon-based reductant, 1-methyl-3,6 bis(trimethylsilyl)-1,4-cyclohexadiene. Reductive cleavage of the C-Cl bond of polyhaloalkanes is accomplished by trichlorotantalum complexes having dianionic alpha-diimine ligands via electron transfer from the dianionic ligands, whereas oxidative decomposition of tetraphenylborate is observed using tetrachlorotantalum complexes with monoanionic alpha-diimine ligands through electron transfer to the monoanionic ligands. Chemically oxidized or reduced complexes of (alpha-diimine)TaCl(4) are isolated as ligand-centered redox products, [Cp(2)Co][(alpha-diimine)TaCl(4)] and [(alpha-diimine)TaCl(4)][WCl(6)], where the alpha-diimine ligand coordinates to the metal center as a dianionic or neutral ligand, respectively. On the basis of EPR measurements of (alpha diimine)TaCl(4) complexes (which are key intermediates for reductive cleavage of C-Cl bond and oxidative decomposition of tetraphenylborate), two redox isomers--a tantalum-centered radical and ligand-localized radical--are present in solution. PMID- 21981372 TI - Pooling designs for outcomes under a Gaussian random effects model. AB - Due to the rising cost of laboratory assays, it has become increasingly common in epidemiological studies to pool biospecimens. This is particularly true in longitudinal studies, where the cost of performing multiple assays over time can be prohibitive. In this article, we consider the problem of estimating the parameters of a Gaussian random effects model when the repeated outcome is subject to pooling. We consider different pooling designs for the efficient maximum likelihood estimation of variance components, with particular attention to estimating the intraclass correlation coefficient. We evaluate the efficiencies of different pooling design strategies using analytic and simulation study results. We examine the robustness of the designs to skewed distributions and consider unbalanced designs. The design methodology is illustrated with a longitudinal study of premenopausal women focusing on assessing the reproducibility of F2-isoprostane, a biomarker of oxidative stress, over the menstrual cycle. PMID- 21981373 TI - Sphere-to-rod transitions of nonionic surfactant micelles in aqueous solution modeled by molecular dynamics simulations. AB - Control of the size and agglomeration of micellar systems is important for pharmaceutical applications such as drug delivery. Although shape-related transitions in surfactant solutions are studied experimentally, their molecular mechanisms are still not well understood. In this study, we use coarse-grained molecular dynamics simulations to describe micellar assemblies of pentaethylene glycol monododecyl ether (C(12)E(5)) in aqueous solution at different concentrations. The obtained size and aggregation numbers of the aggregates formed are in very good agreement with the available experimental data. Importantly, increase of the concentration leads to a second critical micelle concentration where a transition to rod-like aggregates is observed. This transition is quantified in terms of shape anisotropy, together with a detailed structural analysis of the micelles as a function of aggregation number. PMID- 21981374 TI - Light-induced enantiospecific 4pi ring closure of axially chiral 2-pyridones: enthalpic and entropic effects promoted by H-bonding. AB - Nonbiaryl axially chiral 2-pyridones were synthesized and employed for light induced electrocyclic 4pi ring closure leading to bicyclo-beta-lactam photoproducts in solution. The enantioselectivity in the photoproducts varied from 22 to 95% depending on the reaction temperature and the ability of the axially chiral chromophore to form intramolecular and/or intermolecular H-bonds with the solvent. On the basis of the differential activation parameters, entropic control of the enantiospecificity was observed for 2-pyridones lacking the ability to form H-bonds. Conversely, enthalpy played a significant role for 2 pyridones having the ability to form H-bonds. PMID- 21981375 TI - Evaluation of the efficacy and safety of a CS20(r) protective barrier gel containing OGT compared with topical aciclovir and placebo on functional and objective symptoms of labial herpes recurrences: a randomized clinical trial. AB - BACKGROUND: Topical or systemic antiviral drugs reduce the duration of herpes simplex virus 1 (HSV-1) recurrences but may not alleviate functional symptoms. OBJECTIVES: To assess the efficacy and safety of CS20 (Acura 24((r)) ) protective barrier gel versus topical aciclovir and placebo in resolving functional symptoms in HSV-1 labial recurrences. METHODS: A prospective, randomized, single-centre, assessor-blinded study of CS20 versus topical aciclovir or placebo. The primary endpoint was the total score of four herpes-related functional symptoms (pain, burning, itching, and tingling sensations), evaluated by visual analogue scale (VAS). Secondary endpoints encompassed objective skin changes (oedema, crusting and erythema), evaluated by specific clinical scores. RESULTS: In a study of 106 patients, compared with placebo, a significant improvement in total functional symptom score was observed after 1 day of treatment in the CS20 group, but only after 7 days of treatment in the topical aciclovir group. Burning sensations were significantly reduced by CS20 compared with aciclovir (Days 1-2) or placebo (Days 1-7). Compared to placebo, CS20 significantly reduced pain intensity on Days 1-6. CS20 induced significant and early improvements in the clinical scores for oedema and crusting compared with placebo. Time to cure was similar for CS20 and aciclovir. The treatments were well tolerated and adverse events were comparable in the three treatment groups. Limitations The single-centre and single-blind design of the study and the preselection of patients. CONCLUSION: CS20 showed superior effectiveness against functional symptoms (pain and burning) associated with HSV-1 labial recurrences and was similar to aciclovir for time to cure. PMID- 21981376 TI - Patterns of trauma in conflict victims from Timor Leste. AB - Understanding population-level trauma patterns has implications for the recognition of war crimes and crimes against humanity. Trauma data were abstracted from autopsy and anthropology reports for 105 victims from the 1999 conflict in Timor Leste. A significant number of individuals displayed no evidence of injury. No trauma was found in 25% of the sample, while a further 5% had only minor, nonlethal wounds. Where trauma was evident, sharp force injuries were most common (35%), followed by gunshot (20%) and blunt force (13.33%). Timorese frequencies of trauma differ significantly from percentages found in prior reports of mass killings from Cambodia, Bosnia, Croatia, and Afghanistan but closely resemble reported trauma patterns in Rwanda. Decomposition and percentage of body recovered were shown to have a significant impact on the presence/absence of trauma. Complete, fleshed remains were 10.4 times more likely than skeletal remains to have evidence of major or lethal trauma. PMID- 21981377 TI - Intermittent chemotherapy in advanced colorectal cancer: is it the future? PMID- 21981378 TI - Enzyme-linked immunoassay for plasma-free metanephrines in the biochemical diagnosis of phaeochromocytoma in adults is not ideal. AB - BACKGROUND: The aim of the study was to define the analytical and diagnostic performance of the Labor Diagnostica Nord (LDN) 2-Met plasma ELISA assay for fractionated plasma metanephrines in the biochemical diagnosis of phaeochromocytoma. METHODS: The stated manufacturer's performance characteristics were assessed. Clinical utility was evaluated against liquid chromatography tandem mass spectrometry (LC-MS/MS) using bias, sensitivity and specificity outcomes. Samples (n=73) were collected from patients in whom phaeochromocytoma had been excluded (n=60) based on low probability of disease, repeat negative testing for urinary fractionated catecholamines and metanephrines, lack of radiological and histological evidence of a tumour and from a group (n=13) in whom the tumour had been histologically confirmed. Blood collected into k(2)EDTA tubes was processed within 30 min. Separated plasma was aliquoted (*2) and frozen at -40 degrees C prior to analyses. One aliquot was analysed for plasma metanephrines using the LDN 2-Met ELISA and the other by LC-MS/MS. RESULTS: The mean bias of -32% for normetanephrine (ELISA) when compared to the reference method (LC-MS/MS) makes under-diagnosis of phaeochromocytoma likely. The sensitivity of the assay (100%) was equal to the reference method, but specificity (88.3%) lower than the reference method (95%), making it less than optimum for the biochemical diagnosis of phaeochromocytoma. CONCLUSIONS: Plasma free metanephrines as measured by Labor Diagnostica Nord (LDN) 2-Met ELISA do not display test characteristics that would support their introduction or continuation as part of a screening protocol for the biochemical detection of phaeochromocytoma unless the calibration problem identified is corrected and other more accurate and analytically specific methods remain unavailable. PMID- 21981380 TI - From "clinical proteomics" to "clinical chemistry proteomics": considerations using quantitative mass-spectrometry as a model approach. AB - Clinical Proteomics biomarker discovery programs lead to the selection of putative new biomarkers of human pathologies. Following an initial discovery phase, validation of these candidates in larger populations is a major task that recently started relying upon the use of mass spectrometry approaches, especially in cases where classical immune-detection methods were lacking. Thanks to highly sensitive spectrometers, adapted measurement methods like selective reaction monitoring (SRM) and various pre-fractionation methods, the quantitative detection of protein/peptide biomarkers in low concentrations is now feasible from complex biological fluids. This possibility leads to the use of similar methodologies in clinical biology laboratories, within a new proteomic field that we shall name "Clinical Chemistry Proteomics" (CCP). Such evolution of Clinical Proteomics adds important constraints with regards to the in vitro diagnostic (IVD) application. As measured values of analytes will be used to diagnose, follow-up and adapt patient treatment on a routine basis; medical utility, robustness, reference materials and clinical feasibility are among the new issues of CCP to consider. PMID- 21981381 TI - Alcohol promotes mammary tumor development via the estrogen pathway in estrogen receptor alpha-negative HER2/neu mice. AB - BACKGROUND: Alcohol consumption is an established risk factor for breast cancer. Yet, the mechanism by which alcohol affects breast cancer development remains unresolved. The transition from the premenopausal to the postmenopausal phase is associated with a drastic reduction in systemic estrogen levels. It is not clear whether the risk of breast cancer attributable to alcohol consumption is modified by the different levels of estrogen found in pre- and postmenopausal women. The objective of this study is to determine whether the effects of alcohol on mammary tumor development are dependent on the presence of ovarian estrogen. METHODS: As a model of breast cancer, we used mouse mammary tumor virus (MMTV)-neu transgenic mice that overexpress the human epidermal growth factor receptor 2 (HER2/neu) in the mammary epithelium, resulting in the development of estrogen receptor alpha (ERalpha)-negative mammary tumors. The mammary tumorigenesis process in these mice is similar to that of patients with HER2 breast cancer. Nonovariectomized (NOVX) and ovariectomized (OVX) MMTV-neu mice were exposed to 0, 5, and 20% ethanol in the drinking water. Breast cancer development and progression were determined alongside the effects of alcohol on estrogen availability and signaling. RESULTS: Our data show that 20% alcohol consumption promoted tumor development in MMTV-neu mice only in the presence of ovarian hormones. Tumor promotion was associated with increased systemic estrogen levels, increased expression of aromatase (the rate-limiting enzyme in estrogen synthesis), and increased expression of ERalpha in the tumors of 20% alcohol-consuming MMTV-neu mice. Additionally, we show that ovariectomy (removal of the ovaries and ovarian hormone production) blocked the effects of 20% alcohol on tumor development. CONCLUSIONS: Our results support the notion that alcohol consumption promotes HER2 breast cancer development via the estrogen signaling pathway. Additionally, they suggest that the effects of alcohol on breast cancer may be prevented by blocking estrogen signaling. PMID- 21981382 TI - Adaptive responses to alloxan-induced mild oxidative stress ameliorate certain tauopathy phenotypes. AB - Oxidative stress is considered to promote aging and age-related disorders such as tauopathy. Although recent reports suggest that oxidative stress under certain conditions possesses anti-aging properties, no such conditions have been reported to ameliorate protein-misfolding diseases. Here, we used neuronal and murine models that overexpress human tau to demonstrate that mild oxidative stress generated by alloxan suppresses several phenotypes of tauopathy. Alloxan treatment reduced HSP90 levels and promoted proteasomal degradation of tau, c-Jun N-amino terminal kinase, and histone deacetylase (HDAC) 6. Moreover, reduced soluble tau (phosphorylated tau) levels suppressed the formation of insoluble tau in tau transgenic mice, while reduced HDAC6 levels contributed to microtubule stability by increasing tubulin acetylation. Age-dependent decreases in HDAC2 and phospho-tau levels correlated with spatial memory enhancement in alloxan-injected tau mice. These results suggest that mild oxidative stress, through adaptive stress responses, operates counteractively against some of the tauopathy phenotypes. PMID- 21981383 TI - Melasma: treatment strategy. AB - Melasma, a hypermelanosis of the face, is a common skin problem of middle-aged women of all racial groups, especially with dark complexion. Its precise etio pathogenesis is evasive, genetic influences, exposure to sunlight, pregnancy, oral contraceptives, estrogen-progesterone therapies, thyroid dysfunction, cosmetics, and drugs have been proposed. Centro-facial, malar, and mandibular are well-recognized. Epidermal pigmentation appears brown/black, while dermal is blue in color, and can be distinguished by Wood's lamp illumination. The difference may be inapparent with mixed type of melasma in skin types V and VI. An increase in melanin in epidermis: basal and suprabasal layers and/or dermis is the prime defect. There is an increased expression of tyrosinase related protein-1 involved in eumelanin synthesis. The use of broad-spectrum sunscreen is important, lightening agents like retinoic acid (tretinoin), azelaic acid, and combination therapies containing hydroquinone, tretinoin, and corticosteroids, have been used in the treatment of melasma, and are thought to have increased efficacy as compared with monotherapy. Quasi-drugs, placental extracts, ellagic acid, chamomilla extract, butylresorcinol, tranexamic acid, methoxy potassium salicylate, adenosine monophosphate disodium salt, dipropyl-biphenyl-2,2'-diol, (4-hydroxyphenyl)-2-butanol, and tranexamic acid cetyl ester hydrochloride, in addition to kojic and ascorbic acid have been used. Chemical peeling is a good adjunct. Laser treatment is worthwhile. PMID- 21981384 TI - Influenza-associated bacterial pathogens in patients with 2009 influenza A (H1N1) infection: impact of community-associated methicillin-resistant Staphylococcus aureus in Queensland, Australia. AB - BACKGROUND: Secondary bacterial pneumonia due to community onset methicillin resistant Staphylococcus aureus (MRSA) has become a highly publicised cause of influenza-associated death. There is a risk that case reports of fatal outcomes with post-influenza MRSA pneumonia may unduly influence antibiotic prescribing. AIMS: The aim of this study was to demonstrate the incidence of community-onset MRSA pneumonia in 2009 H1N1 influenza patients. METHODS: The microbiology records of patients positive for influenza A (H1N1) in 2009 were reviewed for positive blood or respiratory tract cultures and urinary pneumococcal antigen results within a Queensland database. Patients with such positive results within 48 h of hospital admission and a positive H1N1 influenza result in the prior 6 weeks were included. RESULTS: In 2009, 4491 laboratory-confirmed pandemic influenza A (H1N1) infections were detected. Fifty patients (1.1% of the H1N1 cohort) who were hospitalised with H1N1 and who had a bacterial respiratory tract pathogen were identified. Streptococcus pneumoniae (16 patients; 32%), Staphylococcus aureus (13 patients; 26%) and Haemophilus influenzae (9 patients; 18%) were the most commonly cultured organisms. Of the cohort of 4491 patients, MRSA was detected in only two patients, both of whom were admitted to intensive care units and survived after prolonged admissions. CONCLUSIONS: Influenza-associated community onset MRSA pneumonia was infrequently identified in the 2009 H1N1 season in Queensland, despite community-onset MRSA skin and soft tissue infections being very common. Although post-influenza MRSA pneumonia is of great concern, its influence on empiric-prescribing guidelines should take into account its incidence relative to other secondary bacterial pathogens. PMID- 21981385 TI - Using the Theory of Planned Behaviour and implementation intentions to predict and facilitate upward family communication about mammography. AB - Regular mammography facilitates early detection of breast cancer, and thus increases the chances of survival from this disease. Daughter-initiated (i.e. upward) communication about mammography within mother-daughter dyads may promote mammography to women of screening age. The current study examined this communication behaviour within the context of the Theory of Planned Behaviour (TPB), and aimed to bridge the intention-behaviour gap by trialling an implementation intention (II) intervention that aimed to facilitate upward family communication about mammography. Young women aged 18-39 (N=116) were assigned to either a control or experimental condition, and the latter group formed IIs about initiating a conversation with an older female family member about mammography. Overall, those who formed IIs were more likely to engage in the target communication behaviour, however the intervention was most effective for those who reported low levels of intention at baseline. Perceived behavioural control emerged as the most important variable in predicting the target behaviour. The altruistic nature of this behaviour, and the fact that it is not wholly under volitional control, may have contributed to this finding. Future studies that systematically explore the relative roles of intention and perceived behavioural control in behaviours of this nature are warranted. PMID- 21981386 TI - Hepatitis B virus transmission by blood transfusion during 4 years of individual donation nucleic acid testing in South Africa: estimated and observed window period risk. AB - BACKGROUND: Since October 2005, a total of 2,921,561 blood donations have been screened by the South African National Blood Service for hepatitis B virus (HBV) by individual-donation nucleic acid testing (ID-NAT). Over 4 years, 149 hepatitis B surface antigen-negative acute-phase HBV NAT-positive donations were identified (1:19,608). The lookback program identified one probable HBV transmission. STUDY DESIGN AND METHODS: The complete genomes of HBV isolated from the donor and recipient were sequenced, cloned, and analyzed phylogenetically. The HBV window period (WP) transmission risk was estimated assuming a minimum infectious dose of 3.7 HBV virions and an incidence rate correction factor of 1.34 for transient detectability of HBV DNA. RESULTS: Of 149 acute-phase HBV NAT yields, 114 (1:25,627) were classified as pre-antibody to hepatitis B core antigen (anti-HBc) WP and 35 (1:83,473) as post-anti-HBc WP. The acute-phase transmission risk in the HBV DNA-negative pre- and post-anti-HBc WPs (of 15.3 and 1.3 days, respectively) was estimated at 1:40,000 and 1:480,000, respectively. One HBV transmission (1:2,900,000) was identified in a patient who received a transfusion from an ID-NAT-nonreactive donor in the pre-anti-HBc WP. Sequence analysis confirmed transmission of HBV Subgenotype A1 with 99.7% nucleotide homology between donor and recipient strains. The viral burden in the infectious red blood cell unit was estimated at 32 (22-43) HBV DNA copies/20 mL of plasma. CONCLUSION: We report the first known case of transfusion-transmitted HBV infection by blood screened using ID-NAT giving an observed HBV transmission rate of 0.34 per million. The estimated pre-acute-phase transmission risk in the ID-NAT screened donor population was 73-fold higher than the observed WP transmission rate. PMID- 21981387 TI - Diversification in Adelomyia hummingbirds follows Andean uplift. AB - The Andes are known to have influenced speciation patterns in many taxa, yet whether species diversification occurred simultaneously with their uplift or only after uplift was complete remains unknown. We examined both the phylogenetic pattern and dates of branching in Adelomyia hummingbirds in relation to Andean uplift to determine whether diversification coincides with the chronological phases of the uplift or with recent climatic fluctuations after Andean formation. Results suggest that the genus Adelomyia originated in the central Andes in the Miocene and was found to be comprised of six deeply divergent phylogroups dating between 3.5 and 6 Ma. The most basal splits in the tree, corresponding to the most southerly distributed of the six phylogroups, diverged in the late Miocene, whereas the northern phylogroups originated during the early-to-mid-Pliocene, when the northern Andes reached heights sufficient to support Adelomyia populations. Although we provide evidence for a southern origin for the group, the subsequent diversification of the northern phylogroups did not strictly follow the hypothesized south-to-north orogeny of the Andes. Further genetic structure within phylogroups may have resulted from Pleistocene climate fluctuations after the onset of the six lineages during the Mio-Pliocene. We explore the processes that promoted diversification in the Andes and suggest that in at least some groups, divergence was coupled to Andean orogeny. PMID- 21981393 TI - Study of IspH, a key enzyme in the methylerythritol phosphate pathway using fluoro-substituted substrate analogues. AB - IspH, a [4Fe-4S]-cluster-containing enzyme, catalyzes the reductive dehydroxylation of 4-hydroxy-3-methyl-butenyl diphosphate (HMBPP) to isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) in the methylerythritol phosphate pathway. Studies of IspH using fluoro-substituted substrate analogues to dissect the contributions of several factors to IspH catalysis, including the coordination of the HMBPP C(4)-OH group to the iron-sulfur cluster, the H-bonding network in the active site, and the electronic properties of the substrates, are reported. PMID- 21981394 TI - Phenotypic variability in a family with haemophilia B and prothrombin G20210A. PMID- 21981403 TI - Long-term clinical outcome of thin-strut cobalt-chromium stents in the drug eluting stent era: results of the COBALT (comparison of bare-metal stents in all comers' lesion treatment) registry. AB - BACKGROUND: Despite widespread penetration of drug-eluting stents (DES) in clinical practice, a relevant percentage of patients with coronary artery disease are still treated with bare-metal stents (BMS). Contemporary BMS, however, are less well investigated and comparative data on clinical outcome are lacking. METHODS AND RESULTS: This single-center registry aimed to assess characteristics and outcome of patients treated with 2 different new-generation cobalt-chromium BMS, the MULTI-LINK VISION and PRO-Kinetic stents. During the study, adopted criteria for BMS selection were: (1) limited compliance to dual antiplatelet therapy, (2) ST-elevation myocardial infarction (MI) or saphenous vein graft (SVG) interventions, and (3) noncomplex lesions located either in the right coronary artery or in the nonproximal segments of the left coronary artery. During a 24-month period 1,176 patients were treated with the VISION (n = 438) or PRO-Kinetic stent (n = 738). Median duration of follow-up was 549.5 and 528.5 days, respectively. Target lesion revascularization (TLR) and target vessel revascularization were numerically lower in the VISION group (10.4 vs. 12.3% and 11.9 vs. 15.2%, P = 0.24 and 0.11). Death (4.1 vs. 4.3%, P = 0.85), MI (2 vs. 2.3%, P = 0.78), and ARC definite stent thrombosis (0.5 vs. 0.5%, P = 0.84) were similar. By multivariate analysis, variables associated with TLR were SVG interventions (HR 2.21, 95% CI 1.26-3.86), total stent length (HR 1.01, 95% CI 1.00-1.02), and smoking (HR 1.51, 95% CI 1.05-2.16). CONCLUSION: In the DES era, the use of last-generation thin-strut BMS in selected patients is associated with acceptable clinical outcome, with similar clinical results for both the MULTI LINK VISION and PRO-Kinetic stents. PMID- 21981404 TI - Development of the participation and environment measure for children and youth: conceptual basis. AB - PURPOSE: The purpose of this paper is to describe the conceptual foundation of a new parent-report measure of the participation and environment of children and youth: the Participation and Environment Measure - Children and Youth version (PEM-CY). METHODS: The ICF-CY provided an initial conceptual framework. Results from a qualitative study to obtain parent perspectives and in-depth review of the literature were used to identify relevant dimensions, items and rating scales for measurement. RESULTS: Life situations, defined as sets of activity categories, were identified for three settings: home, school and community. Participation was operationalized as a multidimensional construct with three measurement dimensions: frequency, extent of involvement and desire for change. Parallel sets of items examining environmental factors that are perceived to help or facilitate participation were defined in relation to the typical activities of each setting. CONCLUSIONS: The PEM-CY provides a new measure of participation and environment that reflects the perspectives of parents of children and youth. The instrument will facilitate research and professional practice to understand and support the participation of children and youth with and without disabilities. PMID- 21981405 TI - Difference in soft tissue response between immediate and delayed delivery suggests a new mechanism for recombinant human bone morphogenetic protein 2 action in large segmental bone defects. AB - The ability of recombinant human bone morphogenetic protein 2 on absorbable collagen sponge (rhBMP2/ACS) to regenerate bone in segmental defect has been well characterized. However, clinical results of rhBMP2/ACS constructs in secondary reconstruction of large mandibular and craniofacial defects have not been consistent. We hypothesized that rhBMP2 delivery triggers an endogenous response in the soft tissues surrounding the defect, in the form of expression of BMP2 and vascular endothelial growth factor (VEGF). Such osteogenic response will occur only after immediate, as opposed to delayed, rhBMP2 delivery, suggesting a new explanation to the difference in bone regeneration between the two settings. A 35 mm segmental bone and periosteum defect was created on one side of the mandible in 16 dogs divided in three groups. Group 1 (Gp1, n=6) ACS was loaded with 8 mL of rhBMP2 (0.2 mg/mL). In Gp2 (n=5) the same dose of rhBMP2/ACS was delivered into the defect 4 weeks after surgery. In Gp3 (control; n=5) the defect was reconstructed using ACS loaded with 8 mL of buffer only (devoid of rhBMP2). Tissues were collected after 12 weeks of reconstruction in all groups. Direct measurement of physical dimensions of regenerates and bone morphometry was performed to evaluate bone regeneration. The mRNA expression of both BMP2 and VEGF in the soft tissue surrounding the defect was evaluated using real-time quantitative PCR. Both BMP2 and VEGF proteins were quantified in immunostained sections. Immunoflurescence colocalization of BMP2 and acetylated low density lipoprotein (AcLDL) was done to detect the source of BMP2. Immediate delivery yielded better bone regeneration. Both BMP2 and VEGF mRNA expression was upregulated only in Gp1 (+7.3, p=0.001; +1.53, p=0.001, respectively). BMP2 protein was significantly higher in the immediate reconstruction group; however, VEGF protein was undetected in the examined sections. Immediate delivery of rhBMP2 seemed to induce endogenous release of BMP2 from the surrounding soft tissues, an effect that was lacking in delayed delivery and may explain the variability of clinical results associated with BMP2 use. Colocalization of BMP2 and endothelial cells (ECs) suggested that ECs could be the source of endogenous BMP2. PMID- 21981406 TI - Utility of desmoglein ELISA in the clinical correlation and disease monitoring of pemphigus vulgaris. AB - BACKGROUND: Pemphigus vulgaris (PV) is a relatively common autoimmune blistering disease in India. Recently, enzyme-linked immunosorbent assay (ELISA) test against desmoglein1 (Dsg 1) and desmoglein3 (Dsg 3) has been developed, which is found to be highly sensitive and specific. OBJECTIVE: To assess the utility of ELISA for monitoring the disease of PV. METHODS: Serum samples from 63 active PV patients were tested for anti-Dsg1 and anti-Dsg3 using ELISA. They were tested for anti-Dsg1 and anti-Dsg3 reactivity before treatment. The test was performed during remission period and after relapse using commercially available ELISA kit. RESULTS: Both anti-Dsg1 and anti-Dsg3 levels were found to be raised in PV patients. Thirty-eight patients went on remission during treatment phase with mean anti-Dsg1 and anti-Dsg3 values, 13.18 U/mL and 18.89 U/mL respectively. Difference of baseline from remission was found to be significant (P < 0.001). Of these, 23 patients relapsed either during treatment phase or after stoppage of therapy and their mean anti-Dsg1 and anti-Dsg3 titres were 39.49 U/mL and 96.99 U/mL respectively. Difference of remission from relapse was also found to be significant (P < 0.001). The 50 U/mL cut-off for anti-Dsg1 ELISA provided 73.91% sensitivity and 72.5% specificity respectively. The 98.57 U/mL cut-off for anti Dsg3 provided 82.61% sensitivity and 82.5% specificity respectively. CONCLUSION: ELISA is less time consuming, less expensive and a potential diagnostic test for PV. It is also highly sensitive and specific test for Indian patients in whom the mean anti-Dsg titres are raised. PMID- 21981407 TI - Animal-related fatalities--part II: characteristic autopsy findings and variable causes of death associated with envenomation, poisoning, anaphylaxis, asphyxiation, and sepsis. AB - In addition to blunt and sharp trauma, animal-related fatalities may result from envenomation, poisoning, anaphylaxis, asphyxiation, and sepsis. Although the majority of envenomation deaths are caused by hornets, bees, and wasps, the mechanism of death is most often anaphylaxis. Envenomation resulting from the injection of a poison or toxin into a victim occurs with snakes, spiders, and scorpions on land. Marine animal envenomation may result from stings and bites from jellyfish, octopus, stonefish, cone fish, stingrays, and sea snakes. At autopsy, the findings may be extremely subtle, and so a history of exposure is required. Poisoning may also occur from ingesting certain fish, with three main forms of neurotoxin poisoning involving ciguatera, tetrodotoxin ingestion, and paralytic shellfish poisoning. Asphyxiation may follow upper airway occlusion or neck/chest compression by animals, and sepsis may follow bites. Autopsy analysis of cases requires extensive toxinological, toxicological, and biochemical analyses of body fluids. PMID- 21981408 TI - The pivotal role of intracellular calcium in oxaliplatin-induced inhibition of neurite outgrowth but not cell death in differentiated PC12 cells. AB - The antineoplastic efficacy of oxaliplatin, a widely used anticancer drug, is restricted by its adverse effects such as peripheral neuropathy. Infusing a combination of calcium gluconate and magnesium sulfate (Ca/Mg) suppresses the acute neurotoxic side effects of oxaliplatin, although the mechanism is unclear. To elucidate the molecular mechanisms of oxaliplatin-induced neurotoxicity and the effects of Ca/Mg against this toxicity, we examined the effect of Ca/Mg on oxaliplatin-induced inhibition of neurite outgrowth in PC12 cells, a commonly used neuronal cell model. Oxaliplatin and oxalate suppressed nerve growth factor (NGF)-induced neurite outgrowth and reduced the NGF-mediated increase in the intracellular calcium concentration [Ca(2+)](i). A calcium-chelating agent, BAPTA/AM, also exhibited similar inhibitory effects on neurite outgrowth and [Ca(2+)](i). The addition of Ca/Mg attenuated these inhibitions induced by oxaliplatin and oxalate. The NGF-induced upregulation of growth-associated protein-43 (GAP-43) was suppressed by oxaliplatin and oxalate. Oxaliplatin, but not oxalate, suppressed NGF-stimulated extracellular signal-regulated kinase activation, and this inhibition was not affected by Ca/Mg. Ca/Mg did not modify the oxaliplatin-induced loss of cell viability or apoptosis in PC12 or HCT-116 cells, a human colorectal cancer cell line. These results suggest that the inhibition of neurite outgrowth but not tumor cell death induced by oxaliplatin is partly associated with reductions in [Ca(2+)](i) and GAP-43 expression, and this inhibition was suppressed by the addition of Ca/Mg. Therefore, it may be assumed that Ca/Mg is useful for protecting against oxaliplatin-induced neurotoxicity without reducing the antitumor activity of oxaliplatin. PMID- 21981409 TI - Biomolecular filters for improved separation of output signals in enzyme logic systems applied to biomedical analysis. AB - Biomolecular logic systems processing biochemical input signals and producing "digital" outputs in the form of YES/NO were developed for analysis of physiological conditions characteristic of liver injury, soft tissue injury, and abdominal trauma. Injury biomarkers were used as input signals for activating the logic systems. Their normal physiological concentrations were defined as logic-0 level, while their pathologically elevated concentrations were defined as logic-1 values. Since the input concentrations applied as logic 0 and 1 values were not sufficiently different, the output signals being at low and high values (0, 1 outputs) were separated with a short gap making their discrimination difficult. Coupled enzymatic reactions functioning as a biomolecular signal processing system with a built-in filter property were developed. The filter process involves a partial back-conversion of the optical-output-signal-yielding product, but only at its low concentrations, thus allowing the proper discrimination between 0 and 1 output values. PMID- 21981410 TI - A plastid protein NUS1 is essential for build-up of the genetic system for early chloroplast development under cold stress conditions. AB - During early chloroplast differentiation, the regulation of the plastid genetic system including transcription and translation differs greatly from that in the mature chloroplast, suggesting the existence of a stage-dependent mechanism that regulates the chloroplast genetic system during this period. The virescent-1 (v(1)) mutant of rice (Oryza sativa) is temperature-conditional and develops chlorotic leaves under low-temperature conditions. We reported previously that leaf chlorosis in the v(1) mutant is caused by blockage of the activation of the chloroplast genetic system during early leaf development. Here we identify the V(1) gene, which encodes a chloroplast-localized protein NUS1. Accumulation of NUS1 specifically occurred in the pre-emerged immature leaves, and is enhanced by low-temperature treatment. The C-terminus of NUS1 shows structural similarity to the bacterial antitermination factor NusB, which is known to play roles in the regulation of ribosomal RNA transcription. The RNA-immunoprecipitation and gel mobility shift assays indicated that NUS1 binds to several regions of chloroplast RNA including the upstream leader region of the 16S rRNA precursor. In the leaves of the NUS1-deficient mutant, accumulation of chloroplast rRNA during early leaf development was impaired and chloroplast translation/transcription capacity was severely suppressed under low temperature. Our results suggest that NUS1 is involved in the regulation of chloroplast RNA metabolism and promotes the establishment of the plastid genetic system during early chloroplast development under cold stress conditions. PMID- 21981411 TI - Intracorporeal neobladder reconstruction: pressure-flow urodyamic studies in cadaveric orthotopic neobladders. AB - OBJECTIVE: To determine the pressure-flow characteristics of neobladders created in various configurations that may be constructed intra-abdominally. Complete intracorporeal neobladder construction has been previously described but is limited due to excessive operative time and the need for an advanced laparoscopic skill set. MATERIALS AND METHODS: Four neobladder configurations were constructed, each using 20 cm of human cadaveric small intestine. The standard hand sewn Studer pouch was compared with a circular loop, W-pouch, and U-pouch with stapled anastamoses. Pressure flow studies were completed using the Aquarius TT UDS system (Laborie Medical Technologies, Toronto, Ontario) and each neobladder was filled to a pressure of 50 cm H2O. Neobladder change in pressure, capacity, and overall compliance were determined. RESULTS: The cystometric capacities of the stapled U-pouch, W-pouch, Circle pouch, and Studer pouch were 167.3 mL, 177.5 mL, 114 mL, and 145.2 mL respectively. The first increase in intravesical pressure was at 90.3 mL, 103 mL, 50 mL, and 85 mL. The greatest compliance of 3.81 mL/cmH2O was demonstrated in the U-pouch, with the W-pouch revealing a compliance of 3.44 mL/cmH2O. The least compliant neobladder was the circle pouch (2.24 mL/cmH20) followed by the standard Studer pouch (2.94 mL/cmH2O). CONCLUSION: The construction of an orthotopic neobladder must not only be technically feasible but maintain adequate capacity and compliance for optimal functioning. Pressure-flow studies demonstrated equivalent results in alternate neobladder configurations. Additional data is needed to determine feasibility in vivo. PMID- 21981412 TI - A space-time conditional intensity model for invasive meningococcal disease occurrence. AB - A novel point process model continuous in space-time is proposed for quantifying the transmission dynamics of the two most common meningococcal antigenic sequence types observed in Germany 2002-2008. Modeling is based on the conditional intensity function (CIF), which is described by a superposition of additive and multiplicative components. As an epidemiological interesting finding, spread behavior was shown to depend on type in addition to age: basic reproduction numbers were 0.25 (95% CI 0.19-0.34) and 0.11 (95% CI 0.07-0.17) for types B:P1.7 2,4:F1-5 and C:P1.5,2:F3-3, respectively. Altogether, the proposed methodology represents a comprehensive and universal regression framework for the modeling, simulation, and inference of self-exciting spatiotemporal point processes based on the CIF. Usability of the modeling in biometric practice is promoted by an implementation in the R package surveillance. PMID- 21981413 TI - Fluorous metal-organic frameworks with superior adsorption and hydrophobic properties toward oil spill cleanup and hydrocarbon storage. AB - We demonstrate that fluorous metal-organic frameworks (FMOFs) are highly hydrophobic porous materials with a high capacity and affinity to C(6)-C(8) hydrocarbons of oil components. FMOF-1 exhibits reversible adsorption with a high capacity for n-hexane, cyclohexane, benzene, toluene, and p-xylene, with no detectable water adsorption even at near 100% relative humidity, drastically outperforming activated carbon and zeolite porous materials. FMOF-2, obtained from annealing FMOF-1, shows enlarged cages and channels with double toluene adsorption vs FMOF-1 based on crystal structures. The results suggest great promise for FMOFs in applications such as removal of organic pollutants from oil spills or ambient humid air, hydrocarbon storage and transportation, water purification, etc. under practical working conditions. PMID- 21981414 TI - Comparison of the stem-loop and linear probe-based electrochemical DNA sensors by alternating current voltammetry and cyclic voltammetry. AB - Here we systematically characterized the sensor performance of the stem-loop probe (SLP) and linear probe (LP) electrochemical DNA sensors using alternating current voltammetry (ACV) and cyclic voltammetry (CV), with the goal of generating the set of operational criteria that best suits each sensor architecture, in addition to elucidating the signaling mechanism behind these sensors. Although the LP sensor shows slightly better % signal suppression (SS) upon hybridization with the perfect match target at 10 Hz, our frequency dependent study suggests that it shows optimal % SS only in a very limited AC frequency range. Similar results are observed in CV studies in which the LP sensor, when compared to the SLP sensor, displays a narrower range of voltammetric scan rates where the optimal % SS can be achieved. More importantly, the difference between the two sensors' performance is particularly pronounced if the change in integrated charge (Q) upon target hybridization, rather than the peak current (I), is measured in CV. The temperature-dependent study further highlights the differences between the two sensors, where the LP sensor, owing to the flexible linear probe architecture, is more readily perturbed by temperature changes. Both SLP and LP sensors, however, show a loss of % SS when operated at elevated temperatures, despite the significant improvement in the hybridization kinetics. In conjunction with the ACV, CV, and temperature-dependent studies, the electron-transfer kinetics study provides further evidence in support of the proposed signaling mechanism of these two sensors, in which the SLP sensor's signaling efficiency and sensor performance is directly linked to the hybridization-induced conformational change in the redox-labeled probe, whereas the performance of the LP sensor relies on the hybridization-induced change in probe dynamics. PMID- 21981415 TI - Theoretical comparison of p-nitrophenyl phosphate and sulfate hydrolysis in aqueous solution: implications for enzyme-catalyzed sulfuryl transfer. AB - Both phosphoryl and sulfuryl transfers are ubiquitous in biology, being involved in a wide range of processes, ranging from cell division to apoptosis. Additionally, it is becoming increasingly clear that enzymes that can catalyze phosphoryl transfer can often cross-catalyze sulfuryl transfer (and vice versa). However, while there have been extensive experimental and theoretical studies performed on phosphoryl transfer, the body of available research on sulfuryl transfer is comparatively much smaller. The present work presents a direct theoretical comparison of p-nitrophenyl phosphate and sulfate monoester hydrolysis, both of which are considered prototype systems for probing phosphoryl and sulfuryl transfer, respectively. Specifically, free energy surfaces have been generated using density functional theory, by initial geometry optimization in PCM using the 6-31+G* basis set and the B3LYP density functional, followed by single-point calculations using the larger 6-311+G** basis set and the COSMO continuum model. The resulting surfaces have been then used to identify the relevant transition states, either by further unconstrained geometry optimization or from the surface itself where possible. Additionally, configurational entropies were evaluated using a combination of the quasiharmonic approximation and the restraint release approach and added to the calculated activation barriers as a correction. Finally, the overall activation entropy was estimated by approximating the solvent contribution to the total activation entropy using the Langevin dipoles solvation model. We have reproduced both the experimentally observed activation barriers and the observed trend in the activation entropies with reasonable accuracy, as well as providing a comparison of calculated and observed (15)N and (18)O kinetic isotope effects. We demonstrate that, counterintuitively, the hydrolysis of the p-nitrophenyl sulfate proceeds through a more expansive pathway than its phosphate analogue. Additionally, we show that the solvation effects upon moving from the ground state to the transition state are quite different for both reactions, suggesting that the enzymes that catalyze these reactions would need active sites with quite different electrostatic preorganization for the efficient catalysis of either reaction (despite which many enzymes can catalyze both phosphoryl and sulfuryl transfer). We believe that such a comparative study is an important foundation for understanding the molecular basis for phosphate-sulfate cross-promiscuity within members of the alkaline phosphatase superfamily. PMID- 21981416 TI - Chirality in gold nanoclusters probed by NMR spectroscopy. AB - We report the analysis of chirality in atomically precise gold nanoclusters by nuclear magnetic resonance (NMR) spectroscopic probing of the surface ligands. The Au(38)(SR)(24) and Au(25)(SR)(18) (where, R = CH(2)CH(2)Ph) are used as representative models for chiral and nonchiral nanoclusters, respectively. Interestingly, different (1)H signals for the two germinal protons in each CH(2) of the ligands on the chiral Au(38)(SR)(24) nanocluster were observed, so-called diastereotopicity. For alpha-CH(2) (closest to the chiral metal core), a chemical shift difference of up to ~0.8 ppm was observed. As for the nonchiral Au(25)(SCH(2)CH(2)Ph)(18)(-)TOA(+) nanocluster, no diastereotopicity was detected (i.e., no chemical shift difference for the two protons in the CH(2)), confirming the Au(25) core being nonchiral. These two typical examples demonstrate that NMR spectroscopy can be a useful tool for investigating chirality in Au nanoclusters. Since the diastereotopicity induced on the methylene protons by chiral nanoclusters is independent of the enantiomeric composition of the chiral particles, NMR can probe the chirality of the nanoclusters even in the case of a racemic mixture, while circular dichroism spectroscopy is not useful for racemic mixtures. PMID- 21981417 TI - Patient preferences for diabetes management among people with type 2 diabetes in Denmark - a discrete choice experiment. AB - OBJECTIVES: To study patient preferences for diabetes-treatment related attributes among people with type 2 diabetes. RESEARCH DESIGN AND METHODS: Participants were recruited from three diabetes out-patient clinics and two general practitioner surgeries. Data were collected electronically and results were analysed using a standard statistical model designed for choice sets (conditional logit). Six characteristics relating to treatment of diabetes were examined: glycated haemoglobin level (HbA(1c)), weight (gain or loss), hypoglycaemic events, need for injections, transient nausea and need for blood glucose testing. RESULTS: Two hundred and seventy participants with type 2 diabetes (178 males; 92 females) were included. Patients placed the most value on losing weight and were willing to pay the most to lose 6 kg of weight. Loss of 3 kg of weight was the next highly valued, followed by dropping one percentage point in HbA(1c) level. Avoidance of nausea and a reduction in hypoglycaemic events from two per month to none was also highly valued. Patients were willing to accept one injection per day if they, for instance, simultaneously lost 1.4 kg. A limitation of the study is that the survey was web-based and response rates for such surveys can be extremely variable. CONCLUSION: Patients with type 2 diabetes in Denmark were willing to pay for the health benefits associated with improved diabetes treatment, the most important of these being weight loss or avoidance of weight gain, and reduction of HbA(1c) and of hypoglycaemic events. PMID- 21981418 TI - Post-treatment outcomes in a double-blind, randomized trial of sertraline for alcohol dependence. AB - BACKGROUND: Pharmacotherapy studies in alcohol dependence (AD) are generally of short duration and do not include post-treatment follow-up. We examined the durability of treatment effects in a placebo-controlled trial of sertraline for AD. METHODS: As previously reported, patients received 12 weeks of treatment with sertraline (n = 63) or placebo (n = 71), followed by assessments at 3 and 6 months post-treatment (Kranzler et al., 2011, J Clin Psychopharmacol 31:22-30). We examined the main and interaction effects with time of 3 between-subject factors (medication group, age of onset of AD [late-onset alcoholics, LOAs, vs. early-onset alcoholics, EOAs], and the tri-allelic 5-HTTLPR genotype) on drinking days (DDs) and heavy drinking days (HDDs). RESULTS: The medication group effect, which was significant during treatment, remained significant during the 3-month follow-up period for L'/L' LOAs, with the sertraline group having fewer DDs than the placebo group (p = 0.027). However, the medication group effect seen in L'/L' EOAs during treatment was no longer significant (p = 0.48). There were no significant effects in S' carriers at the 3-month follow-up visit, or in either genotype group at the 6-month follow-up. CONCLUSIONS: The beneficial effects of sertraline observed in LOAs during treatment persisted during the 3-month post treatment period. Additional studies are needed to validate these pharmacogenetic findings, which together with the effects seen during active treatment support the use of sertraline only in LOAs. PMID- 21981419 TI - Dysregulated expression of miR-146a contributes to age-related dysfunction of macrophages. AB - Age-associated immune dysfunction, characterized by increased systemic levels of cytokines, manifests as an increased susceptibility to infections. Thus, understanding these negative regulators of the immune response has paved the way to delineating signaling pathways that impact immune senescence. In the present study, we found that miR-146a, which negatively regulated the expression of IL 1beta and IL-6, was highly expressed in aged mice. However, there was a lack of response to the stimulation of lipopolysaccharide (LPS) and proinflammatory cytokines in macrophages of aged mice. As a result, the negative feedback regulation loop with miR-146a involving down-regulation of inflammation factors was interrupted in aged mice. Aberrant NF-kappaB binding to the miR-146a promoter was demonstrated to be associated with the abnormal expression of miR-146a in aged mice. The DNA methyltransferase inhibitor (5-aza-2-deoxycytidine) and the histone deacetylase inhibitor [trichostatin A (TSA)] both significantly up regulated miR-146a transcriptional activation by altering the DNA-binding activity of NF-kappaB in macrophages isolated from aged mice, which suggests that DNA methylation and histone acetylation are involved in the suppression of age dependent miR-146a expression. Additionally, high levels of histone deacetylase (HDACs) expressions contributed to the inhibition of miR-146a expression in LPS stimulated macrophages from aged mice in vitro. While the suppression of HDACs activities by TSA could improve LPS-induced inflammatory responses owing to up regulation of miR-146a expression in macrophages from aged mice. These data indicate that the dysregulated expression of miR-146a results in the age associated dysfunction of macrophages, and miR-146a may be a good target for the treatment of age-related inflammatory diseases. PMID- 21981420 TI - Time will tell: a retrospective study investigating the relationship between insomnia and objectively defined punctuality. AB - Primary insomnia is a prevalent sleep disorder affecting approximately 3% of the general population. Studies suggest that personality traits such as perfectionism and neuroticism might be implicated in the aetiology of the disorder. However, to date, no study has investigated behavioural indicators of these factors in a hypothesis-driven manner. In the present study, we assessed punctuality as a behavioural indicator of perfectionism and neuroticism in 635 consecutive clinical patients of the sleep laboratory of the Department of Psychiatry and Psychotherapy, University of Freiburg Medical Center. The primary aim was to compare primary insomnia patients (n = 148) with another group of patients with other sleep-related diagnoses (n = 487). Primary insomnia patients arrived on average 4 min earlier when compared to other patients (P = 0.041). However, this effect failed to reach statistical significance when correcting for the influence of potential confounding variables. Of note, we found a strong relationship between polysomnographic sleep parameters and punctuality. That is, short sleep duration was associated significantly with early arrival times at the sleep laboratory (P = 0.023). These findings support the proposal that personality traits, which we predict underlie obsessive punctuality, may be involved in the aetiology of objectively defined sleep disturbances. Clinical implications of the current results for cognitive behavioural treatments of insomnia are discussed. PMID- 21981421 TI - Treatment decisions and usage of clotting factor concentrate by a cohort of Indian haemophilia patients. PMID- 21981422 TI - A novel vaccine delivery system: biodegradable nanoparticles in thermosensitive hydrogel. AB - In this work, a novel vaccine delivery system, biodegradable nanoparticles (NPs) in thermosensitive hydrogel, was investigated. Human basic fibroblast growth factor (bFGF)-loaded NPs (bFGF-NPs) were prepared, and then bFGF-NPs were incorporated into thermosensitive hydrogel to form bFGF-NPs in a hydrogel composite (bFGF-NPs/hydrogel). bFGF-NPs/hydrogel was an injectable sol at ambient temperature, but was converted into a non-flowing gel at body temperature. The in vitro release profile showed that bFGF could be released from bFGF-NPs or bFGF NPs/hydrogel at an extended period, but the release rate of bFGF-NPs/hydrogel was much lower. In vivo experiments suggested that immunogenicity of bFGF improved significantly after being incorporated into the NPs/hydrogel composite, and strong humoral immunity was maintained for longer than 12 weeks. Furthermore, an in vivo protective anti-tumor immunity assay indicated that immunization with bFGF-NPs/hydrogel could induce significant suppression of the growth and metastases of tumors. Thus, the NPs/hydrogel composite may have great potential application as a novel vaccine delivery system. PMID- 21981423 TI - Natural history of side branches jailed by drug-eluting stents. AB - BACKGROUND: Stent deployment across side branch (SB) ostium is common in daily practice. The present study investigated the natural history of SBs jailed by drug-eluting stents (DES). METHODS: The thrombolysis in myocardial infarction (TIMI) flow grades of 271 consecutive SBs jailed by DES in 196 patients was assessed immediately after the procedure and at 9 months of follow-up. Patients receiving any SB intervention were excluded. RESULTS: Of 271 jailed SBs, occlusion occurred in 6.27% and deterioration of flow occurred in 6.27% immediately after stenting. In patients with these SB changes, periprocedural myocardial infarction was more likely than in those without (10.0% vs. 1.8%, P = 0.017), while there was no increase of cardiac death or life-threatening complications such as stent thrombosis and Q-wave myocardial infarction (Q MI) during follow-up. At 9 months, angiography showed that one-third of the initially obstructed SBs were still occluded. In contrast, flow was maintained in almost all (98.6%) SBs with early TIMI flow grade 3 and there was no delayed occlusion of these branches. Multiple regression analysis showed that lesion complexity (Medina bifurcation class, calcification, and preprocedural TIMI grade 2 flow in the SB) and technical factors (jailing by overlapping stents) were related to SB occlusion or flow deterioration. CONCLUSIONS: Jailed SBs showing good flow after stenting had a favorable angiographic and clinical outcome after 9 months of follow-up. However, preprocedural lesion complexity and technical factors should be considered to avoid SB occlusion/flow deterioration associated with periprocedural myocardial infarction. PMID- 21981424 TI - Rural Victorian Telestroke project. AB - BACKGROUND: Intravenous thrombolysis improves functional outcomes in acute ischaemic stroke. However, many rural stroke patients are denied thrombolysis because of a rural neurologist shortage. 'Telestroke' facilitates thrombolysis by providing remote access to neurologists via videoconferencing systems. AIMS: To develop a safe and feasible Telestroke system in a rural Victorian hospital that facilitates delivery of intravenous thrombolysis to acute ischaemic stroke patients. METHODS: A pilot videoconferencing Telestroke system was set up between Royal Melbourne Hospital and Northeast Health Wangaratta. Acute stroke patients presenting within 4.5 h of symptom onset without intracranial haemorrhage were eligible for Telestroke. However, eligible patients were excluded from Telestroke if they had haemorrhagic risk factors. Data were collected from intervention (October 2009-September 2010) and control group (October 2008-September 2009) by medical file audit. Primary outcome measure was percentage of patients thrombolysed. Secondary outcome measures included incidence of symptomatic intracerebral haemorrhage and door-to-computed tomography time. RESULTS: One hundred and forty-five acute stroke patients presented in control year and 130 patients in intervention year. Fifty-four patients in intervention and 36 patients in control group were eligible for thrombolysis. In intervention group, 24 patients had Telestroke activated and 8 patients underwent thrombolysis. There was no thrombolysis in the control group. There were neither symptomatic intracerebral haemorrhages nor deaths attributable to thrombolysis. Median door to-computed tomography time did not significantly differ between eligible patients in control and intervention groups. CONCLUSION: Telestroke has the potential to bridge the gap of rural-metropolitan inequality in acute stroke care. Our Telestroke system successfully introduced safe thrombolysis and early specialist review of acute stroke patients in rural Victoria. PMID- 21981432 TI - Investigating outcomes following the use of selective serotonin reuptake inhibitors for treating depression in pregnancy: a focus on methodological issues. AB - The aim of this review was to critically appraise the existing literature with a particular focus on identifying methodological issues associated with studying outcomes following the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy. Existing studies evaluating outcomes following prenatal SSRI exposure suffer from a number of important methodological limitations that should be taken into account when interpreting their results. The contradictory results obtained from prospective and retrospective cohort studies and case-control studies could be accounted for by dissimilarity between study populations, selection bias, detection bias, confounding, or differences in underlying maternal illness, data sources used, exposure classification, follow-up and statistical power/analysis. Only a small number of studies actually account for underlying maternal illness and how this may lead to adverse pregnancy outcomes. Even when such information is available, studies that include data on maternal illness have small sample sizes, limiting the statistical power to identify statistically and clinically relevant associations. Pregnancy outcomes may be confounded by the higher incidence of smoking, alcohol consumption and substance abuse frequently encountered amongst those suffering from depression, factors that are often insufficiently controlled for. While evidence of associations between prenatal SSRI exposure and adverse pregnancy outcomes are conflicting, there is an urgent need to evaluate how the particular SSRI used, the dose, timing and duration of use, genetics (maternal, paternal and/or fetal), concomitant medication use, maternal characteristics and underlying maternal illness all interact to alter pregnancy outcomes. PMID- 21981433 TI - Biochemical monitoring of patients treated with antihypertensive therapy for adverse drug reactions: a systematic review. AB - Biochemical monitoring of patients treated with antihypertensive therapy is recommended in order to identify potential adverse reactions to treatment. We aimed to review the literature investigating the nature of biochemical monitoring in adults treated in primary care with antihypertensive drugs. Specifically, we wished to establish (i) the proportion of patients with biochemical baseline testing prior to the initiation of antihypertensive therapy; (ii) the proportion of patients with biochemical monitoring after initiation of antihypertensive therapy; (iii) the patient characteristics associated with biochemical monitoring; (iv) the frequency of biochemical monitoring after the initiation of antihypertensive therapy; and (v) the relationship, if any, between biochemical monitoring and adverse patient outcomes. We searched MEDLINE, EMBASE and Google Scholar from 1948 to 31 December 2010 using a combination of text words and search terms. Retrospective and prospective cohort studies, cross-sectional studies, randomized controlled trials or quasi-randomized controlled trials, and audits of current clinical practice were included. Clinical trials, case reports and case series were excluded. Studies were included if they provided data on the proportion of patients treated with antihypertensive therapy in primary care who had any biochemical monitoring before or after the initiation of therapy. In total, 15 studies were included in our review, which used a wide variety of definitions of monitoring prior to and after the initiation of antihypertensive therapy. From 17% to 81% of patients treated with antihypertensive drugs had a baseline biochemical test and from 20% to 79% had any follow-up monitoring. In only 7 of the 12 studies that examined follow-up monitoring did more than half of the patients have any monitoring. Overall, this systematic review provides evidence that monitoring as recommended by published guidelines is not commonly undertaken. Only two studies were identified that examined patients with both baseline testing and follow-up monitoring. Omission of one or the other limits the ability to analyse the effect of treatment on electrolyte concentrations or renal function. There is limited research on the patient factors associated with monitoring and further work is required to determine the impact of monitoring on adverse patient outcomes. Important barriers to effective monitoring exist and this review emphasizes that these have not yet been overcome. PMID- 21981434 TI - Androgen deprivation therapy and the risk of coronary heart disease and heart failure in patients with prostate cancer: a nested case-control study in UK primary care. AB - BACKGROUND: Androgen deprivation therapy (ADT) is used to delay tumour development and improve survival in patients with prostate cancer. However, several randomized controlled trials and observational studies have suggested that ADT may increase the risk of cardiovascular events. OBJECTIVE: The aim of the study was to evaluate the risk of coronary heart disease (CHD) and heart failure (HF) in patients with prostate cancer receiving ADT in UK primary care, and to evaluate the risks associated with individual ADT and combination ADT. METHODS: The UK General Practice Research Database was used to identify a cohort of patients with a first prostate cancer diagnosis during 1999-2005. These patients were followed up to assess the occurrence of acute myocardial infarction (AMI), death from CHD, incident HF and hospitalization due to acute decompensated HF. Nested case-control analyses were performed to assess the risk of these outcomes associated with anti-androgen therapy, as well as different types of ADT and combinations of ADT. RESULTS: Current anti-androgen use was associated with a significant increase in the risk of hospitalization due to HF (odds ratio [OR] 2.15; 95% CI 1.08, 4.29), but not of incident HF, CHD or AMI. When assessed individually, there was no significant association of bicalutamide or cyproterone use with the risk of AMI or CHD. Current use of bicalutamide 50 mg/day was associated with a significant increase in the risk of HF (OR 3.28; 95% CI 1.31, 8.18); however, this increased risk of HF was only found in patients taking bicalutamide 50 mg/day in combination with luteinizing hormone-releasing hormone (LHRH) receptor agonists. There were no cases of hospitalized HF in patients taking bicalutamide 50 mg/day as monotherapy and there was no significant association between current use of bicalutamide 150 mg/day and the risk of hospitalized HF. Combination therapy with LHRH agonists and anti-androgens was associated with a significant increase in the risk of CHD (OR 4.35; 95% CI 1.94, 9.75), AMI (OR 3.57; 95% CI 1.44, 8.86), incident HF (OR 3.19; 95% CI 1.10, 9.27) and hospitalized HF (OR 3.39; 95% CI 1.07, 10.70) compared with non-use of these drugs. CONCLUSIONS: In men with prostate cancer, combination therapy with LHRH agonists and anti-androgens is associated with significant increases in the risk of CHD, AMI, incident HF and hospitalized HF. Individual therapies do not appear to increase the risk of these outcomes. PMID- 21981435 TI - Opioid-paracetamol prescription patterns and liver dysfunction: a retrospective cohort study in a population served by a US health benefits organization. AB - BACKGROUND: Paracetamol (acetaminophen) is the most common cause of acute liver failure (ALF). ALF attributed to paracetamol is most often associated with the following features: an unintentional overdose, a single product, an opioid paracetamol combination, duration of <7 days, and a median dose of 7.5 g/day. Currently, the recommended maximum daily dose of paracetamol is 4 g. OBJECTIVES: The aims of the study were to determine opioid-paracetamol prescription patterns, including prescriptions exceeding the recommended dose of paracetamol (4 g/day) [prescriptions and beneficiaries]; examine factors associated with receiving opioid-paracetamol prescriptions in excess of paracetamol 4 g/day; and evaluate opioid-paracetamol prescription patterns for beneficiaries with liver dysfunction. METHODS: A retrospective cohort study examining prescription data of 4.8 million beneficiaries from a US health benefits organization from 1 January 2009 through 31 December 2009. The main outcomes examined were daily paracetamol dose and liver dysfunction. RESULTS: A large proportion (8.1%) of the 5.3 million prescriptions for opioid-paracetamol exceeded the recommended maximum daily dose of paracetamol (4 g/day), putting over one-quarter of a million (255 123 [18.9%]) of the 1.35 million beneficiaries receiving an opioid-paracetamol prescription at risk of toxicity. The most frequently prescribed products that exceeded paracetamol dose guidelines contained dextropropoxyphene and hydrocodone. Multiple factors, including type of product (i.e. dextropropoxyphene or oxycodone containing), geographical location (Midwest), strength of the paracetamol in the opioid-paracetamol product (>325 mg) and prescriber specialty (dentist, physician assistant), were associated with high-dose paracetamol prescriptions. Liver dysfunction was diagnosed in 3818 cases, and 23.4% of these beneficiaries received an opioid-paracetamol prescription in the 90 days prior to the liver dysfunction diagnosis. CONCLUSIONS: Although most opioid-paracetamol prescriptions are written and dispensed for <4 g/day of paracetamol, a significant portion of beneficiaries are being prescribed and dispensed excessive doses of paracetamol. Efforts to curtail this practice may involve provision of prescriber and pharmacist education, utilization of benefit manager systems to flag excessive dosing or that require confirmation of dosing, and implementation of US FDA recommendations supported by these data. PMID- 21981436 TI - Preventable and non-preventable adverse drug events in hospitalized patients: a prospective chart review in the Netherlands. AB - BACKGROUND: Medication safety research and clinical pharmacy practice today is primarily focused on managing preventable adverse drug events (pADEs). Determinants of both pADEs and non-preventable adverse drug reactions (ADRs) have been identified. However, relatively little is known on the overlap between these determinants and the balance of preventable and non-preventable harm inpatients experience in modern computerized hospitals. OBJECTIVE: The aim of this study was to analyse the prevalence of pADEs and non-preventable ADRs as well as the determinants, including multimorbidity, of these ADEs, i.e. both pADEs and ADRs. METHODS: Adverse events experienced by patients admitted to two Dutch hospitals with functioning computerized physician order entry (CPOE) systems were prospectively identified through chart review. Adverse events were divided into pADEs (i.e. as a result of a medication error) and non-preventable ADRs. In both cases, a causal relationship between adverse events and patients' drugs was established using the simplified Yale algorithm. Study data were collected anytime between April 2006 and May 2008 over a 5-month period at each hospital ward included in the study, beginning from 8 weeks after CPOE was implemented at the ward. RESULTS: pADEs and non-preventable ADRs were experienced by 349 (58%) patients, of whom 307 (88%) had non-preventable ADRs. Multimorbidity (adjusted odds ratio [OR(adj)] 1.90; 95% CI 1.44, 2.50; OR(adj) 1.28; 95% CI 1.14, 1.45, respectively), length of stay (OR(adj) 1.13; 95% CI 1.06, 1.21; OR(adj) 1.11; 95% CI 1.07, 1.16, respectively), admission to the geriatric ward (OR(adj) 7.78; 95% CI 2.15, 28.13; OR(adj) 3.82; 95% CI 1.73, 8.45, respectively) and number of medication orders (OR(adj) 1.25; 95% CI 1.16, 1.35; OR(adj) 1.13; 95% CI 1.06, 1.21, respectively) were statistically significantly associated with pADEs and ADRs. Admission to the gastroenterology/rheumatology ward (OR(adj) 0.22; 95% CI 0.06, 0.77; OR(adj) 0.40; 95% CI 0.24, 0.65, respectively) was inversely related to both pADEs and ADRs. Other determinants for ADRs only were female sex (OR(adj) 1.77; 95% CI 1.12, 2.80) and use of drugs affecting the nervous system (OR(adj) 1.83; 95% CI 1.09, 3.07). Age was a significant determinant for pADEs only (OR(adj) 1.07; 95% CI 1.03, 1.11). CONCLUSIONS: In this study more than half of the patients admitted to the hospitals are harmed by drugs, of which most are non serious, non-preventable ADRs (after the introduction of CPOE). Determinants of both pADEs and ADRs overlap to a large extent. Our results imply the need for signalling early potential adverse events that occur during the normal use of drugs in multimorbid patients or those in geriatric wards. Subsequent therapeutic interventions may improve the well-being of hospitalized patients to a greater extent than focusing on errors in the medication process only. PMID- 21981437 TI - Effect of safety issues with HIV drugs on the approval process of other drugs in the same class: an analysis of European Public Assessment Reports. AB - BACKGROUND: Knowledge on the safety of new medicines is limited at the time of market entry. Nearly half of all drugs used to treat HIV registered in the EU required >=1 Direct Healthcare Professional Communication (DHPC) in the past 10 years for safety issues identified post-approval. OBJECTIVE: The aim was to evaluate the extent to which regulators and industry have addressed the risk of safety issues for HIV drugs based on prior experience with other drugs in the same class and whether doing so impacts development time of these drugs. METHODS: HIV drugs receiving >=1 DHPC in the Netherlands between January 1999 and December 2008 were identified. Each drug with a DHPC ('index' drug) was paired with subsequently approved HIV drug(s) in the same class (Anatomical Therapeutic Chemical [ATC] 4th level) ['follow-on' drugs]. Characteristics of safety issues were extracted from the DHPCs of the 'index' drugs. European Public Assessment Reports (EPARs) were reviewed regarding whether the safety issues had been considered during development and approval. Consideration of previously identified safety issues in 'follow-on' drug applications was assessed regarding attention paid to adverse drug reaction (ADR) symptoms in pre-marketing studies, Summary of Product Characteristics (SmPC) and postmarketing commitments, and whether size of the safety population was in accordance with Regulatory guidelines. 'Index' drugs were also paired with drugs in the same class already on the market ('older' drugs). For 'older' drugs, we identified whether the safety issue led to appropriate changes in the current SmPC (January 2011) compared with the SmPC at the time of marketing authorization. Clinical development time was assessed using time from first patent application to market authorization as proxy, and comparison was made between 'index' and 'follow-on' drugs. RESULTS: For 9 (43%) of the 21 centrally authorized HIV drugs, 11 serious safety issues that required a DHPC were identified. Two drugs were excluded from our analysis (DHPCs related to contamination/medication error). Six 'index' drugs were paired, each with one to six 'follow-on' drugs. Three concerned drug-drug interactions (DDIs); the other three were intracranial haemorrhage, neuromuscular weakness and severe skin/hepatic reactions. All but one 'follow-on' drug had information in the EPAR on that specific ADR (i.e. attention was paid to the ADR). The DDIs were addressed in pre-marketing studies and/or the SmPC. Two of the other ADRs were addressed by postmarketing surveillance commitments; intracranial haemorrhage was not addressed. Three safety issues for two 'index' drugs could not be paired with a 'follow-on' drug as no drug in the same class was approved after the corresponding DHPCs were issued. Five of the nine safety issues were added to at least one of the current SmPCs for the 'older' drugs already on the market at the time of DHPC issue. Two safety issues were already in the SmPC of the 'older' drugs at time of market approval and two were not introduced into the SmPC of 'older' drugs. Population size to assess short-term safety complied with the guidelines for four 'index', seven 'follow-on' and three 'older' drugs; population size to assess long-term safety complied for one, three and two drugs, respectively. For five drugs, EPARs did not provide adequate information on population size. No statistically significant difference in development time between 'index' and 'follow-on' drugs was found. CONCLUSION: Generally, safety issues were taken into account in the approval process of other drugs in the class. The approaches were different and determined by the nature of the ADR. Taking safety issues into account in the approval process did not seem to impact on the time taken to perform the pre-approval clinical programme. PMID- 21981438 TI - Patient reporting encouraged during monitoring of dapoxetine in New Zealand. PMID- 21981439 TI - Volume-reduced platelet concentrates: optimization of production and storage conditions. AB - BACKGROUND: Plasma can be removed from platelet (PLT) concentrates (PCs) when volume reduction for PLT transfusion is indicated. Volume-reduced PCs are currently produced from pooled buffy coat (BC) PCs or apheresis PCs by pretransfusion volume reduction, followed by transfer to a syringe for immediate transfusion. We evaluated the maximal storage time of the volume-reduced PCs in gas-permeable containers. STUDY DESIGN AND METHODS: Volume-reduced PCs were produced from BC-derived and apheresis PCs by hard-spin centrifugation. Supernatant was removed and the PLTs were resuspended in 20 mL of retained original PC and had PLT concentrations ranging from 10.8 * 10(9) to 13.8 * 10(9) PLTs/mL. Volume-reduced PCs were stored either in syringes or in containers made from diethylhexyl phthalate (DEHP)-polyvinylchloride (PVC) or butyryl trihexyl citrate (BTHC)-PVC plastic. Units were sampled at t = 0, 1, 3, and 6 hours for in vitro measurements. RESULTS: When prepared from 2-day-old PCs (n = 4), volume reduced PCs from BCs in a syringe had a pH(37 degrees C) of 5.76 +/- 0.04 at t = 6 hours after volume reduction. In the DEHP-PVC container, pH was 5.85 +/- 0.15 (not significant), and in the BTHC-PVC, 6.34 +/- 0.16 (p < 0.001), at t = 6 hours. When made from 7-day-old PCs, pH was lower for all storage conditions: 5.68 +/- 0.06 in the syringe, 5.70 +/- 0.09 in the DEHP-PVC container (not significant), and 6.07 +/- 0.24 in the BTHC-PVC container (p < 0.01) at t = 6 hours. Volume-reduced 2-day-old apheresis PCs had a pH of 6.47 +/- 0.20 at t = 6 hours. CONCLUSIONS: Adult-dose PCs derived from BC or apheresis can be volume reduced to approximately 20 mL in a closed gas-permeable system. Volume-reduced PCs in BTHC-PVC containers retain a mean pH of more than 6.0 up to 6 hours after production. Syringes allow only 3 hours of storage. PMID- 21981441 TI - Body shaping with acoustic wave therapy AWT((r))/EPAT((r)): randomized, controlled study on 14 subjects. AB - INTRODUCTION: Reduction of localised adiposities by non invasive means is a very frequent request among the female and male population. OBJECTIVE: The objective of this study is to demonstrate the efficacy and safety of AWT((r)), combining two different mechanical waves, planar AWT and radial AWT during the same session, in volume reduction of saddle bags in women. METHODS: Treatment was performed on the saddle bag areas of 14 female patients, with the CELLACTOR((r)) SC1 (Storz Medical AG, Tagerwilen, Switzerland) using extracorporeal pulse activation technology, EPAT((r)). This device includes two handpieces, the C ACTOR((r)) and the D-ACTOR((r)). Within 4 weeks, eight AWT((r)) treatment sessions have been performed with both applicators. Follow-up visits were performed 1, 4 and 12 weeks after the last treatment. RESULTS: Measurements with the ultrasound system clearly demonstrate a significant diminution in the subcutaneous fat layer thickness and a reduction of the averaged circumference of thighs. CONCLUSIONS: This study, although performed on a small number of patients, tends to show the safety and efficacy of AWT((r)) in treating localized fat areas in a non-invasive way. There is also an additional benefit for patients in reducing the cellulite appearance and improving the skin firmness at the same time by using AWT((r)). PMID- 21981443 TI - ICF Core Set for vocational rehabilitation: results of an international consensus conference. AB - PURPOSE: Vocational rehabilitation (VR) programs aim to facilitate work participation. However, there is no universal framework to describe the functioning of individuals who participate in VR. The objective of this paper is to report on the Core Set for VR based on the International Classification of Functioning, Disability and Health (ICF) by the World Health Organization (WHO). METHODS: A formal decision-making and consensus-based process was conducted based on the evidence from four preparatory studies. Twenty-three international experts chosen by WHO Region and expertise in VR attended the consensus conference. RESULTS: Ninety ICF categories were included in the comprehensive Core Set (activities and participation = 40, environmental factors = 33, body functions = 17), while the brief Core Set included 13 second-level categories (activities and participation = 6, environmental factors = 4, body functions = 3). CONCLUSIONS: The expert opinion and evidence-based Core Set could serve as an international standard for what to measure and report concerning functioning of individuals in VR. The Core Set could also provide a common language among clinicians, researchers, insurers, and policymakers in the implementation of successful VR. Further testing and validation studies are encouraged. PMID- 21981444 TI - Single DNA molecule patterning for high-throughput epigenetic mapping. AB - We present a method for profiling the 5-methyl cytosine distribution on single DNA molecules. Our method combines soft-lithography and molecular elongation to form ordered arrays estimated to contain more than 250 000 individual DNA molecules immobilized on a solid substrate. The methylation state of the DNA is detected and mapped by binding of fluorescently labeled methyl-CpG binding domain peptides to the elongated dsDNA molecules and imaging of their distribution. The stretched molecules are fixed in their extended configuration by adsorption onto the substrate so analysis can be performed with high spatial resolution and signal averaging. We further prove this technique allows imaging of DNA molecules with different methylation states. PMID- 21981445 TI - Chiral 1,2-subnaphthalocyanines. AB - Following the first suggestion of inherent molecular chirality in asymmetrically substituted subphthalocyanines by Torres and co-workers in 2000, elucidation of the relationship between structure and chirality has become an important issue. However, separation of the enantiomers has been prevented by the low solubility of the molecules synthesized to date, and it has not been possible to link the CD signs and intensities to their absolute structures. Recently, we observed that 1,2-subnaphthalocyanines possess two diastereomers with respect to the arrangement of the naphthalene moieties and that these novel chiral molecules exhibit moderate solubility in common organic solvents. This has enabled us to separate all of the diastereomers and enantiomers. The two diastereomers have been completely characterized by NMR spectroscopy and X-ray diffraction analysis. The absorption and magnetic circular dichroism spectra, together with theoretical calculation, reveal a small variation in the frontier molecular orbitals of the 1,2-subnaphthalocyanines compared with conventional subphthalocyanines, except for destabilization of the HOMO-3, which results in a characteristic absorption in the Soret band region. The chirality of 1,2-subnaphthalcyanines, including the CD signs and intensities, is discussed in detail for the first time with enantiomerically pure molecules whose absolute structures have been elucidated by single-crystal X-ray diffraction analysis. PMID- 21981446 TI - Compound heterozygous mutations in desmoplakin cause skin fragility and woolly hair. PMID- 21981447 TI - Sociodemographic and diagnostic characteristics of homicidal and nonhomicidal sexual offenders. AB - The aims of this study were to compare the prevalence of psychiatric disorders and "psychopathy" in homicidal and nonhomicidal sexual offenders and to investigate the specificity of previous studies on psychiatric morbidity of a sample of sexual murderers. Information from court reports of 166 homicidal and 56 nonhomicidal sex offenders was evaluated using standardized instruments (SCID II, PCL-R) and classification systems (DSM-IV). Sexual murderers were diagnosed more often with a personality disorder (80.1% vs. 50%; p < 0.001), especially schizoid personality disorder (16.3% vs. 5.4%; p < 0.05), as well as with sexual sadism (36.7% vs. 8.9%; p < 0.001) and sexual dysfunctions (21.7% vs. 7.1%; p < 0.05). Additionally, they had more often used alcohol during the offense (63.2% vs. 41%; p < 0.05). The results indicate that sexual murderers have more and a greater variety of psychiatric disorders when compared to nonhomicidal sex offenders. PMID- 21981448 TI - Simplest method for creating micropatterned nanostructures on PDMS with UV light. AB - The fabrication of micropatterned structures on PDMS is a critical step in soft lithography, microfluidics, and many other PDMS-based applications. To substitute traditional mold-casting methods, we develop a simple method to create micropatterned nanostructures on PDMS in one step. After exposing a flat PDMS surface to a UV pen lamp through a photomask (such as a TEM grid), micropatterned nanostructures can be formed readily on the PDMS surface. We also demonstrate that fabricated PDMS can be used for the microcontact printing of protein immunoglobulin (IgG) on solid surfaces. This method is probably the simplest method of creating micropatterned nanostructures on PDMS reported so far because it does not need casting, surface coating, or chemical reagents. Only a UV pen lamp and a photomask are required, and this method can be performed under ambient conditions without vacuum. We expect that this method will greatly benefit researchers who use PDMS regularly in various applications such as soft lithography and microfluidics. PMID- 21981449 TI - Bilateral uveitis associated with fluoroquinolone therapy. AB - CONTEXT: Retrospective case series, database study and literature review. Forty case reports are described. OBJECTIVE: To report a possible association between fluoroquinolones and uveitis. MATERIALS AND METHODS: Spontaneous reports from the National Registry of Drug-Induced Ocular Side effects, World Health Organization, and Food and Drug Administration were collected on uveitis associated with systemic fluoroquinolone therapy. A literature review was performed using keywords "uveitis", "fluoroquinolones", and each individual fluoroquinolone name. Additional case reports were collected from the practices of six uveitis subspecialists and one neuro-ophthalmologist. MAIN OUTCOME MEASURES: Data garnered from the reports include the type of fluoroquinolone, age, gender, adverse drug reaction (ADR), dosage, duration of therapy until onset of uveitis, concomitant drugs, systemic disease, dechallenge and rechallenge data. RESULTS: A total of 40 case reports of uveitis associated with fluoroquinolones were identified including 12 men, 27 women, and 1 case in which the gender was not specified. The median age was 54 years. Dosage varied between the different fluoroquinolone drugs, with the median dosage within the range recommended in the package insert for each different fluoroquinolone. Median time from beginning of therapy to appearance of the ADR was 13 days (range 0-20 days). Thirteen patients were 60 years or older, and one patient was taking systemic anti-inflammatory steroids. There were five positive dechallenge case reports. DISCUSSION: According to World Health Organization criteria, the relationship between fluoroquinolone therapy and uveitis is "possible". Causality assessments are based on the time relationship of drug administration, uveitis development, and dechallenge data. CONCLUSIONS: Clinicians should be aware of a possible bilateral fluoroquinolone-associated uveitis, particularly the finding of iris transillumination and pigment dispersion. PMID- 21981450 TI - Shielded hydrogen bonds as structural determinants of binding kinetics: application in drug design. AB - Time scale control of molecular interactions is an essential part of biochemical systems, but very little is known about the structural factors governing the kinetics of molecular recognition. In drug design, the lifetime of drug-target complexes is a major determinant of pharmacological effects but the absence of structure-kinetic relationships precludes rational optimization of this property. Here we show that almost buried polar atoms--a common feature on protein binding sites--tend to form hydrogen bonds that are shielded from water. Formation and rupture of this type of hydrogen bonds involves an energetically penalized transition state because it occurs asynchronously with dehydration/rehydration. In consequence, water-shielded hydrogen bonds are exchanged at slower rates. Occurrence of this phenomenon can be anticipated from simple structural analysis, affording a novel tool to interpret and predict structure-kinetics relationships. The validity of this principle has been investigated on two pairs of Hsp90 inhibitors for which detailed thermodynamic and kinetic data has been experimentally determined. The agreement between macroscopic observables and molecular simulations confirms the role of water-shielded hydrogen bonds as kinetic traps and illustrates how our finding could be used as an aid in structure-based drug discovery. PMID- 21981451 TI - Sustained hyperaemia stimulus is necessary to induce flow-mediated dilation of the human brachial artery. AB - We studied the relative importance of the magnitude and duration of the shear stimulus to induce flow-mediated dilation (FMD) in the brachial artery of 10 healthy men by ultrasound imaging. The shear stress stimulus was induced by different durations of reactive hyperaemia following 15-min forearm occlusion. The control condition of continuous postocclusion hyperaemia was compared to 20, 40 and 60 s of reactive hyperaemia followed by reapplication of circulatory arrest for 2 min and a second cuff release. In response to the first cuff release, peak shear rate was not different between conditions; total shear during the first minute was reduced in the 40 s and further reduced in the 20 s conditions. FMD in control (10.0 +/- 3.0%), 60 s (10.5 +/- 3.2%) and 40 s (7.8 +/ 3.6%) were greater than the 20-s condition (2.9 +/- 2.8%). At second cuff release, peak shear of the 20-s condition was slightly reduced from the first release, but 40 and 60-s conditions were progressively reduced. Total shear to peak dilation was reduced after the second cuff release for the 20 and 40-s conditions and further after the 60-s condition. FMD was maintained in the 20-s condition (8.3 +/- 3.7%) but reduced in the 40-s (3.7 +/- 1.7%) and 60-s conditions (1.5 +/- 2.6%). FMD was not related to peak shear rate after the first occlusion (r = 0.003) but was after the second cuff release (r = 0.32, P = 0.004). The FMD response was correlated with the total shear to time of peak diameter after the first (r = 0.35, P<0.001) and the second (r = 0.25, P = 0.009) cuff release. PMID- 21981452 TI - Reproducibility and variability of digital thermal monitoring of vascular reactivity. AB - BACKGROUND: Previous studies demonstrated that digital thermal monitoring (DTM) of vascular reactivity, a new test for vascular function assessment, is well correlated with Framingham Risk Score, coronary calcium score and CT angiography. This study evaluates the variability and reproducibility of DTM measurements. We hypothesized that DTM is reproducible, and its variability falls within the accepted range of clinical diagnostic tests. METHOD: A fully automated DTM device (VENDYS, Endothelix Inc., Houston, TX, USA) was used for repeated measurement of vascular function in 18 healthy volunteers (age 35 +/- 4 years, 74% men) after 24 h. All subjects underwent overnight fasting, and the test was preceded by 30-min rest in a supine position inside a dimmed room with temperature 22-24 degrees C. The measurements were obtained during and after a 2-min supra systolic arm-cuff occlusion-induced reactive hyperaemia procedure. As a part of this study, the Doppler ultrasound hyperaemic, low-frequency, blood velocity of radial artery and a fingertip DTM of vascular function were compared simultaneously. Postcuff deflation temperature rebound and area under the curve, DTM indices of vascular function, were studied. RESULTS: Temperature rebound area under the curve correlated closely with Doppler hyperaemic, low-frequency, blood velocity (r = 0.97, P = 0.0001). Day-to-day intra-subject variability was 6.2% for baseline temperature, 8.7% for mean blood pressure and 11.4% for heart rate. The coefficient of repeatability of temperature rebound and area under the curve were 2.4% and 2.8%. CONCLUSION: In a controlled environment, the repeatability of DTM is excellent. DTM can be used as a reproducible and operator-independent test for non-invasive measurement of vascular function. PMID- 21981453 TI - The effect of acute blood-flow-restricted resistance exercise on postexercise blood pressure. AB - INTRODUCTION: Blood-flow-restricted (BFR) exercise is an emerging type of exercise that may be particularly beneficial to elderly or special populations. These populations may also benefit from reductions in blood pressure (BP). The effect of BFR exercise on postexercise BP has not been examined; this should first be examined in a young, healthy population as a preliminary investigation. PURPOSE: The main purpose of this study was to determine whether postexercise hypotension (PEH) occurred following low-intensity [20% 1 repetition maximum (1 RM)] BFR resistance exercise. A secondary purpose was to compare this response to both a work-matched low-intensity (20% 1-RM) (LI) and a traditional high intensity (70% 1-RM) resistance exercise bout (HI). METHODS: In a randomized cross-over design, ten normotensive, young (18-35 years) men performed one of the three lower-body resistance exercise bouts (HI, LI or low-intensity BFR) during separate visits to the laboratory. Brachial BP, cardiac ultrasound and calf blood flow measurements were taken prior to and 30 and 60 min following exercise. Repeated measures analysis of variance (3 * 3; condition * time) was performed on all variables. RESULTS: A significant interaction (P<0.05) was found for brachial systolic blood pressure which decreased following HI only. Significant interactions (P<0.05) were also seen for heart rate, total peripheral resistance and calf vascular resistance. CONCLUSION: Postexercise hypotension occurred only following HI. Thus, if one is exercising with the intent of lowering BP, HI resistance exercise may be more useful than low-intensity BFR resistance exercise. PMID- 21981454 TI - TRPV1 and TRPA1 stimulation induces MUC5B secretion in the human nasal airway in vivo. AB - AIM: Nasal transient receptor potential vanilloid 1 (TRPV1) stimulation with capsaicin produces serous and mucinous secretion in the human nasal airway. The primary aim of this study was to examine topical effects of various TRP ion channel agonists on symptoms and secretion of specific mucins: mucin 5 subtype AC (MUC5AC) and B (MUC5B). METHODS: Healthy individuals were subjected to nasal challenges with TRPV1 agonists (capsaicin, olvanil and anandamide), TRP ankyrin 1 (TRPA1) agonists (cinnamaldehyde and mustard oil) and a TRP melastatin 8 (TRPM8) agonist (menthol). Symptoms were monitored, and nasal lavages were analysed for MUC5AC and MUC5B, i.e. specific mucins associated with airway diseases. In separate groups of healthy subjects, nasal biopsies and brush samples were analysed for TRPV1 and MUC5B, using immunohistochemistry and RT-qPCR. Finally, calcium responses and ciliary beat frequency were measured on isolated ciliated epithelial cells. RESULTS: All TRP agonists induced nasal pain or smart. Capsaicin, olvanil and mustard oil also produced rhinorrhea. Lavage fluids obtained after challenge with capsaicin and mustard oil indicated increased levels of MUC5B, whereas MUC5AC was unaffected. MUC5B and TRPV1 immunoreactivities were primarily localized to submucosal glands and peptidergic nerve fibres, respectively. Although trpv1 transcripts were detected in nasal brush samples, functional responses to capsaicin could not be induced in isolated ciliated epithelial cells. CONCLUSION: Agonists of TRPV1 and TRPA1 induced MUC5B release in the human nasal airways in vivo. These findings may be of relevance with regard to the regulation of mucin production under physiological and pathophysiological conditions. PMID- 21981455 TI - The effect of phenylephrine on arterial and venous cerebral blood flow in healthy subjects. AB - AIM: Sympathetic regulation of the cerebral circulation remains controversial. Although intravenous phenylephrine (PE) infusion reduces the near-infrared spectroscopy (NIRS)-determined measure of frontal lobe oxygenation (S(c) O(2) ) and increases middle cerebral artery mean blood velocity (MCA V(mean) ), suggesting alpha-adrenergic-mediated cerebral vasoconstriction, this remains unconfirmed by evaluation of arterial and venous cerebral blood flow. METHODS: We determined S(c) O(2) , MCA V(mean) , and right internal carotid artery (ICA) and internal jugular venous (IJV) blood flow (duplex ultrasound) during infusion of PE in eight supine young healthy men [26 (3) years, 177 (7) cm and 74 (8) kg; mean (SD)]. RESULTS: Compared with saline, during infusion of PE, mean arterial pressure increased 26 +/- 3% (mean +/- SE) and MCA V(mean) by 4.8 +/- 1.9% (P<0.05), while S(c) O(2) decreased by 13.7 +/- 3.7% (P<0.05) with no significant changes in the arterial oxygen or carbon dioxide tensions. ICA blood flow did not change significantly in response to PE administration (351 +/- 12 versus 373 +/- 21 ml min(-1) ; P = 0.236), while IJV blood flow increased (443 +/- 57 versus 507 +/- 58 ml min(-1) ; P = 0.023). CONCLUSIONS: These findings confirm that PE induces a reduction in S(c) O(2) measured by NIRS and causes an increase in MCA V(mean) indicative of cerebral arterial vasoconstriction, although ICA was preserved and IJV increased. These results suggest that a decrease in S(c) O(2) during infusion of PE reflects an altered cerebral contribution of arterial versus venous blood to the NIRS signal, although we cannot rule out that an effect of PE on skin blood flow is important. PMID- 21981456 TI - Limited value of novel pulmonary embolism biomarkers in patients with coronary atherosclerosis. AB - BACKGROUND: Recent research supports the efficacy of various plasma biomarkers in diagnosing pulmonary embolism (PE) including E-selectin, MMP-9, MPO, sVCAM-1, sICAM-1, adiponectin, hs-CRP and tPAI-1. OBJECTIVE: We hypothesized that these biomarkers, which are affected in both venous and arterial thromboembolic diseases, have a limited potential of diagnosing PE in patients with concomitant coronary atherosclerosis, as assessed from a low-dose CT scan of the thorax, compared to patients without atherosclerosis. METHODS: Consecutive patients suspected of PE were referred. All patients had a ventilation/perfusion single photon emission tomography (V/Q-SPECT), low-dose pulmonary CT, pulmonary multidetector computer tomography angiography, blood samples and ECG-gated cardiac CT performed the same day. RESULTS: A total of 69 patients were included, of which 28 (41%) had PE. In patients without coronary calcium, MMP-9 and tPAI-1 were significantly elevated (P<0.042 and P<0.049) in patients diagnosed with PE. From the receiver operating curves, we chose a cut-off value for MMP-9 at 164.4 ng l(-1) , which yielded sensitivity, specificity, positive and negative predictive values of 63%, 78%, 71% and 70%, respectively. With a chosen cut-off value for tPAI-1 at 56.3 ng l(-1) , the sensitivity, specificity, positive and negative predictive values were 88%, 89%, 88% and 89%, respectively. In patients with coronary calcium, none of the biomarkers could discriminate between PE and no PE. CONCLUSION: Plasma levels of tPAI-1 and MMP-9 are potentially useful in patients suspected of PE, however, not in the presence of the coronary atherosclerosis. PMID- 21981457 TI - The dynamics of the microcirculation in the subcutaneous adipose tissue is impaired in the postprandial state in type 2 diabetes. AB - Postprandially, the blood flow and uptake of non-esterified fatty acids increase concomitantly in the abdominal subcutaneous adipose tissue in healthy subjects. In insulin-resistant subjects, this postprandial blood flow increase is blunted. We have previously found that the postprandial adipose tissue blood flow (ATBF) increase is accompanied by capillary recruitment in healthy subjects. The aim of the present study was to investigate whether the postprandial capillary recruitment in adipose tissue is affected in type 2 diabetes mellitus. Eight type 2 diabetic overweight male subjects and eight age- and weight-matched healthy subjects were studied. Contrast-enhanced ultrasound imaging was applied to study the microvascular volume in abdominal subcutaneous adipose tissue and in forearm skeletal muscle in the fasting state and 60, 120 and 180 min after a 75-g oral glucose load. Abdominal subcutaneous ATBF was measured using (133) Xenon washout technique, and forearm skeletal muscle blood flow was assessed by venous occlusion plethysmography. In the healthy, overweight subjects, ATBF increased and concomitantly capillary recruitment took place after glucose ingestion. No significant changes were found in the ATBF or in capillary recruitment in the type 2 diabetic subjects. There was no significant blood flow or microvascular blood volume changes in forearm skeletal muscle in either of the groups. CONCLUSION: After an oral glucose load, the abdominal ATBF and microvascular blood volume changes in abdominal subcutaneous adipose tissue are impaired in overweight type 2 diabetic subjects compared to weight-matched healthy subjects. PMID- 21981458 TI - Arterial tension time reflects subclinical atherosclerosis, arterial stiffness and stroke volume. AB - OBJECTIVE: To introduce and evaluate a new haemodynamic parameter known as arterial tension time (ATT) and study whether ATT is associated with traditional cardiovascular risk factors as well as with indices of arterial stiffness, cardiac pump function and subclinical atherosclerosis. METHODS: Arterial tension time was measured from the whole-body impedance cardiography (ICG) signal and defined as the time difference between the onset of arterial distension induced by stroke volume (SV) and maximal integrated arterial distension. As measures of subclinical atherosclerosis and arterial stiffness, carotid artery intima-media thickness (IMT), Young's elastic modulus (YEM), arterial stiffness index (ASI) and carotid artery compliance (CAC) were assessed with ultrasound in 336 Finnish adults (aged 46-76 years, 43.2% men) participating in the Health 2000 Survey. In addition, pulse wave velocity (PWV) and stroke volume index (SI), as indices of arterial stiffness and cardiac pump function, were assessed with ICG. RESULTS: Arterial tension time was associated inversely with PWV, IMT, YEM and ASI (P<0.002 for all) and directly with SI and CAC (P<0.001 for both). Age, systolic blood pressure, diastolic blood pressure and fasting glucose were independent determinants of decreased ATT (P<0.04 for all). Moreover, accumulation of cardiovascular risk factors was associated with the decrease in ATT (P for trend <0.001). CONCLUSION: Decreased ATT was associated with increased arterial stiffness, increased subclinical atherosclerosis and decreased SV. Current results suggest that ATT provides simultaneous information on several aspects of cardiovascular structure and function and could possibly serve as a new integrated parameter for cardiovascular risk stratification. PMID- 21981459 TI - Effects of walking with blood flow restriction on limb venous compliance in elderly subjects. AB - Venous compliance declines with age and improves with chronic endurance exercise. KAATSU, an exercise combined with blood flow restriction (BFR), is a unique training method for promoting muscle hypertrophy and strength gains by using low intensity resistance exercises or walking. This method also induces pooling of venous blood in the legs. Therefore, we hypothesized that slow walking with BFR may affect limb venous compliance and examined the influence of 6 weeks of walking with BFR on venous compliance in older women. Sixteen women aged 59-78 years were partially randomized into either a slow walking with BFR group (n = 9, BFR walk group) or a non-exercising control group (n = 7, control group). The BFR walk group performed 20-min treadmill slow walking (67 m min(-1) ), 5 days per week for 6 weeks. Before (pre) and after (post) those 6 weeks, venous properties were assessed using strain gauge venous occlusion plethysmography. After 6 weeks, leg venous compliance increased significantly in the BFR walk group (pre: 0.0518 +/- 0.0084, post: 0.0619 +/- 0.0150 ml 100 ml(-1) mmHg(-1) , P<0.05), and maximal venous outflow (MVO) at 80 mmHg also increased significantly after the BFR walk group trained for 6 weeks (pre: 55.3 +/- 15.6, post: 67.1 +/- 18.9 ml 100 ml(-1) min(-1) , P<0.01), but no significant differences were observed in venous compliance and MVO in the control group. In addition, there was no significant change in arm compliance in the BFR walk group. In conclusion, this study provides the first evidence that 6 weeks of walking exercise with BFR may improve limb venous compliance in untrained elder female subjects. PMID- 21981460 TI - Evidence of diminished coronary flow in pulmonary hypertension: explaining angina pectoris in this patient group? AB - BACKGROUND: Many patients with pulmonary hypertension (PH) have symptoms of angina without evidence of occlusive coronary artery disease. For the first time, this study addresses the influence of progressively increasing pulmonary artery pressure (PAP) on left anterior descending artery flow in a rat model of PH. The role of pulmonary artery dilatation, septal wall motion abnormality, cardiac output or diastolic blood pressure in determining coronary blood flow (CBF) during PH was determined. METHODS: Pulmonary hypertension was induced in 6-week old female nude rats (n = 44) using monocrotaline. Animals underwent right heart catheterization and echocardiography, and blood pressure measurement was taken at baseline, 21 and 35 days. RESULTS: A total of 103 echocardiographic studies were carried out at three fixed time points in rats with variable PAP. CBF decreased from 46.6 +/- 14.3 to 24.7 +/- 12.3 cm s(-1) (P<0.001) over time. Pulmonary artery diameter increased from 2.30 +/- 0.19 to 2.83 +/- 0.30 mm (P<0.001), and left ventricular (LV) cardiac output decreased from 143 +/- 23 to 78 +/- 30 ml min(-1) (P<0.001). Using observed solution estimates of 0.00170 (P = 0.0005) and 1.75 (P = 0.006) for these variables, we calculated that CBF increased by 5.90 cm s(-1) (15.6%, CI: 14.5-17.1%) or decreased by -4.86 cm s(-1) (-12.9%, CI: -14.1 11.9%) for every standard deviation increase in LV cardiac output or pulmonary artery diameter, respectively. CBF decreased significantly with increasing PAP. Pulmonary artery diameter and LV cardiac output appear to be independent determinants of coronary flow in PH. CONCLUSIONS: Coronary flow reduction in murine PH has potential to be clinically meaningful and should therefore further studied in a clinical trial. PMID- 21981461 TI - Evaluation of aortic geometries created by magnetic resonance imaging data in healthy volunteers. AB - INTRODUCTION: The development of atherosclerotic plaques has been associated with the patterns of wall shear stress (WSS). However, much is still uncertain with the methods used to calculate WSS. Correct vessel geometries are mandatory to get reliable estimations, and the purpose of this study was to evaluate an in vivo method for creating aortic 3D geometry in human based on data from magnetic resonance imaging (MRI) with ultrasound as reference. METHODS: The aortas of ten healthy men, 23.4 +/- 1.6 years of age, were examined with a 1.5 T MRI system using a 3D gadolinium-enhanced gradient-echo sequence. Three-dimensional geometries were created using manual segmentation of images. Lumen diameters (LD) were measured in the abdominal aorta (AA) and the thoracic aorta (TA) with non invasive B-mode ultrasound as a reference. RESULTS: The anteroposterior diameter of the AA was 13.6 +/- 1.1 mm for the MRI and 13.8 +/- 1.3 mm for the ultrasound (NS). Intraobserver variability (CV) for MRI and ultrasound was <0.92% and <0.40%, respectively. Interobserver variability for MRI and ultrasound was 0.96% and 0.56%, respectively. The diameter of the TA was 19.2 +/- 1.4 mm for the MRI, and the intraobserver variability (CV) was <0.78% and interobserver variability (CV) was 0.92%. CONCLUSION: Specific arterial geometries can be constructed with a high degree of accuracy using MRI. This indicates that the MRI geometries may be used to create realistic and correct geometries in the calculation of WSS in the aorta of human. PMID- 21981462 TI - A comparison of the efficacy of newly developed reversible inhibitors of acetylcholinesterase with commonly used pyridostigmine as pharmacological pre treatment of soman-poisoned mice. AB - The ability of three newly developed reversible inhibitors of acetylcholinesterase (AChE) (K298, K344 and K474) and currently available carbamate pyridostigmine to increase the resistance of mice against soman and the efficacy of antidotal treatment of soman-poisoned mice was compared. Neither pyridostigmine nor new reversible inhibitors of AChE were able to increase the LD(50) value of soman. Thus, the pharmacological pre-treatment with pyridostigmine or newly synthesized inhibitors of AChE was not able to protect mice against soman-induced lethal acute toxicity. The pharmacological pre treatment with pyridostigmine alone or with K474 was able to slightly increase the efficacy of antidotal treatment (the oxime HI-6 in combination with atropine) of soman-poisoned mice, but the increase in the efficacy of antidotal treatment was not significant. The other newly developed reversible inhibitors of AChF (K298, K344) were completely ineffective. These findings demonstrate that pharmacological pre-treatment of soman-poisoned mice with tested reversible inhibitors of AChF is not promising. PMID- 21981463 TI - Urogenital fistula in the UK: a personal case series managed over 25 years. AB - Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Whilst several very large series of obstetric fistulae from the developing world have been published, data on fistulae as seen in the developed world are relatively few. Most fistulae in the UK are known to follow hysterectomy, and several risk factors are recognised. We have confirmed the common association with pelvic surgery, and in particular hysterectomy, but also show the broad range of other associated operations, including so called 'minimally invasive' procedures. High rates of both anatomical fistula closure and continence are shown, when a consistent approach to assessment, selection of surgical procedure, and postoperative care are applied. Successful closure is seen more often in women who have not undergone previous attempts at repair before referral, and as a result a pattern of surpra regional management is proposed. Whilst overall the number of urogenital fistulae seen in the UK appears to be decreasing, there is a suggestion from these data that the rate of fistula formation following hysterectomy may be increasing; we are currently investigating this possibility through detailed interrogation of a national dataset. OBJECTIVE: To review demography, aetiology, surgery and outcomes of women with urogenital fistula seen in one unit over the last 25 years; to provide data for comparison with a parallel study based on Hospital Episode Statistics. PATIENTS AND METHODS: This is a prospective case series from a tertiary urogynaecology centre providing a de facto supra-regional fistula service. The women included had confirmed urogenital fistula referred between January 1986 and December 2010. Index cases were identified from a surgical database; data were entered prospectively and updated as appropriate; statistics are largely descriptive. The primary outcome is the patient's report of absence of urinary leakage. Secondary outcomes include operative or postoperative complications, anatomical closure of the fistula, other residual or new urinary symptoms, and the need for further intervention. RESULTS: In all, 348 women with urogenital fistula were referred; two-thirds were of surgical aetiology, with almost half following hysterectomy. Although 11% followed childbirth, most of these followed operative obstetric interventions. Spontaneous closure occurred in 6.9% of women and 291 underwent surgical treatment. The anatomical closure rate at first operation was 95.7%, although 2.2% reported residual urinary incontinence. The success rates were similar regardless of aetiology, although successful fistula closure was significantly more likely in women who had not had attempts at closure before referral (98.2 vs 88.2%; Fisher's exact test; P= 0.003). CONCLUSION: High rates of fistula closure are reported regardless of aetiology, although previous unsuccessful repair militates against successful outcome; this emphasises the appropriateness of centralisation of the management of this increasingly rare condition in UK practice. PMID- 21981465 TI - Ru-catalyzed asymmetric hydrogenation of gamma-heteroatom substituted beta-keto esters. AB - A series of enantiomerically pure gamma-heteroatom substituted beta-hydroxy esters were synthesized with high enantioselectivities (up to 99.1% ee) by hydrogenation of gamma-heteroatom substituted beta-keto esters in the presence of Ru-(S)-SunPhos catalyst. These asymmetric hydrogenations provide key building blocks for a variety of naturally occurring and biologically active compounds. PMID- 21981464 TI - Positive spillover effects of prescribing requirements: increased cardiac testing in patients treated with trastuzumab for HER2+ metastatic breast cancer. AB - BACKGROUND: Cardiotoxicity is a concern in patients on trastuzumab therapy, and cardiac function assessment is a recommended practice. In 2006, trastuzumab was publically subsidised for human epidermal growth factor receptor-2 early stage breast cancer with a requirement for cardiac testing prior to and during treatment. AIM: To investigate the spillover effects of this requirement on testing rates in metastatic patients treated with trastuzumab where no monitoring requirements are applied. METHODS: We examined cardiac testing (echocardiography or multiple-gated acquisition scan) in 3779 women with metastatic breast cancer receiving trastuzumab between December 2001 and February 2010 and used interrupted time-series analyses to estimate changes in testing rates. The main outcome measures were the proportion of eligible patients, by quarter, receiving a cardiac function test pretreatment and during trastuzumab therapy. RESULTS: Only 21% of women had a cardiac function test pretreatment, and 47% were tested at some point during the first year of trastuzumab therapy. The introduction of mandatory cardiac testing for early breast cancer was associated with an immediate 8% increase (95% confidence interval, 2-14%) in pretreatment cardiac testing and an immediate 7% increase (95% confidence interval, 4-10%) in testing during therapy in metastatic patients. Testing rates during therapy increased steadily from early 2005, coinciding with the release of interim results from several trastuzumab trials reporting cardiac-safety outcomes. CONCLUSION: The introduction of mandatory cardiac testing for early stage disease spilled over to the metastatic setting. While deviation from guidelines may be warranted in some cases, this study suggests underutilisation of cardiac testing among patients treated with trastuzumab in the metastatic setting. PMID- 21981466 TI - Blood transfusion in sickle cell disease. AB - Sickle cell anemia is an inherited disease that causes chronic hemolytic anemia. Its pathognomonic signs and symptoms are caused by hemoglobin (Hb) S, which results from a single nucleotide substitution in the beta-globin gene that places the amino acid valine with glutamic acid at codon 6 of the beta-globin chain. Hb S is an insoluble Hb that crystalizes at low oxygen tension and other precipitating conditions leading to rigidity of red cells and clumping in small blood vessels. Patients with sickle cell disease have a variable Hb level that may range from 7.0 to 11.0 g/dL in their steady state condition. The most common cause of hospital presentation is due to acute painful crisis that results from vaso-occlusion by sickled cells. These episodes are treated with hydration and analgesia and do not require blood transfusion. Blood transfusion should be aimed to increase tissue delivery of oxygen. Hb S is known to be a low affinity Hb and so delivers oxygen at a lower partial pressure of oxygen compared to Hb A. Even with adequate pre transfusion testing and precautions, blood transfusion is never totally safe and short or long term complications may occur. Blood transfusion in patients with sickle cell disease has only limited indications such as acute hemolytic, aplastic or sequestration crises. Chronic transfusion protocols are implemented in cases of strokes or high cerebral blood flow ultrasonic studies as a prophylactic measure. Exchange blood transfusion is used in some complications of the disease such as acute chest syndrome (ACS), priapism or peri operatively. Once it is decided to transfuse blood, the transfused blood should be Hb S negative, Rh and Kell antigen matched. PMID- 21981467 TI - Long-term safety and effectiveness of drug-eluting stents compared to bare metal stents following successful PCI in non-ST-elevation myocardial infarction: findings from the Guthrie Health Off-Label StenT (GHOST) Registry. AB - BACKGROUND: The long-term safety and effectiveness of drug-eluting stents (DES) versus bare metal stents (BMS) in non-ST-segment elevation myocardial infarction (NSTEMI) beyond 2 years after percutaneous coronary intervention (PCI) is unknown. METHODS: We studied 674 NSTEMI patients who underwent successful PCI with DES (n = 323) or BMS (n = 351). The primary study end-points were time to occurrence of death or nonfatal recurrent myocardial infarction (MI), and stent thrombosis (ST). Secondary end-points included time to occurrence of target vessel revascularization (TVR) and any major adverse cardiovascular event (MACE, defined as the composite of death, MI, ST, TVR). RESULTS: The DES and BMS groups were well matched except that DES patients received dual antiplatelet therapy for a longer duration and had smaller final vessel diameter. In survival analysis, at a mean follow-up of 1333 +/- 659 days after PCI, the DES group had similar incidence of death/myocardial infarction (24% vs. 27%, log rank p = 0.23) and ST (4.0% vs. 2.6%, p = 0.18) as the BMS group. The DES patients had lower incidence of TVR (8.1% vs. 17%, p = 0.0018) but similar MACE (26% vs. 37%, p = 0.31). In multivariable analysis, DES vs. BMS implantation showed no significant impact on death/myocardial infarction [adjusted hazards ratio (HR) 1.0, 95% confidence intervals (CI) 0.7-1.4], ST (HR 1.7; CI 0.7 - 4.0), or MACE (HR 0.8; CI 0.6 - 1.1). However, TVR was lower in the DES group (HR 0.4; CI 0.3 - 0.7). CONCLUSION: In patients presenting with NSTEMI, DES implantation appears to be as safe as BMS implantation at long-term follow-up. In addition, DES are effective in reducing TVR compared to BMS. PMID- 21981482 TI - Nonclassical degrees of freedom in the Riemann Hamiltonian. AB - The Hilbert-Polya conjecture states that the imaginary parts of the zeros of the Riemann zeta function are eigenvalues of a quantum Hamiltonian. If so, conjectures by Katz and Sarnak put this Hamiltonian in the Altland-Zirnbauer universality class C. This implies that the system must have a nonclassical two valued degree of freedom. In such a system, the dominant primitive periodic orbits contribute to the density of states with a phase factor of -1. This resolves a previously mysterious sign problem with the oscillatory contributions to the density of the Riemann zeros. PMID- 21981483 TI - Integrability of the Rabi model. AB - The Rabi model is a paradigm for interacting quantum systems. It couples a bosonic mode to the smallest possible quantum model, a two-level system. I present the analytical solution which allows us to consider the question of integrability for quantum systems that do not possess a classical limit. A criterion for quantum integrability is proposed which shows that the Rabi model is integrable due to the presence of a discrete symmetry. Moreover, I introduce a generalization with no symmetries; the generalized Rabi model is the first example of a nonintegrable but exactly solvable system. PMID- 21981484 TI - Nonlocality is transitive. AB - We show a transitivity property of nonlocal correlations: There exist tripartite nonsignaling correlations of which the bipartite marginals between A and B as well as B and C are nonlocal and any tripartite nonsignaling system between A, B, and C consistent with them must be such that the bipartite marginal between A and C is also nonlocal. This property represents a step towards ruling out certain alternative models for the explanation of quantum correlations such as hidden communication at finite speed. Whereas it is not possible to rule out this model experimentally, it is the goal of our approach to demonstrate this explanation to be logically inconsistent: either the communication cannot remain hidden, or its speed has to be infinite. The existence of a three-party system that is pairwise nonlocal is of independent interest in the light of the monogamy property of nonlocality. PMID- 21981485 TI - Measurement-induced chaos with entangled states. AB - The dynamics of an ensemble of identically prepared two-qubit systems is investigated which is subjected to the iteratively applied measurements and conditional selection of a typical entanglement purification protocol. The resulting dynamics exhibits strong sensitivity to initial conditions. For one class of initial states two types of islands characterize the asymptotic limit. They correspond to a separable and a fully entangled two-qubit state, respectively, and their boundaries form fractal-like structures. In the presence of incoherent noise an additional stable asymptotic cycle appears. PMID- 21981486 TI - Selective and efficient quantum process tomography without ancilla. AB - Several methods, known as quantum process tomography, are available to characterize the evolution of quantum systems, a task of crucial importance. However, their complexity dramatically increases with the size of the system. Here we present a new method for quantum process tomography. We describe a new algorithm that can be used to selectively estimate any parameter characterizing a quantum process. Unlike any of its predecessors this new quantum tomographer combines two virtues: it requires investing a number of physical resources scaling polynomially with the number of qubits and at the same time it does not require any ancillary resources. We present the results of the first implementation of this quantum device, characterizing quantum processes affecting two qubits encoded in heralded single photons. Even for this small system our method displays clear advantages over the other existing ones. PMID- 21981487 TI - Quantum fluctuation theorem in an interacting setup: point contacts in fractional quantum Hall edge state devices. AB - We verify the validity of the Cohen-Gallavotti fluctuation theorem for the strongly correlated problem of charge transfer through an impurity in a chiral Luttinger liquid, which is realizable experimentally as a quantum point contact in a fractional quantum Hall edge state device. This is accomplished via the development of an analytical method to calculate the full counting statistics of the problem in all the parameter regimes involving the temperature, the Hall voltage, and the gate voltage. PMID- 21981488 TI - Revealing the physics of R modes in low-mass x-ray binaries. AB - We consider the astrophysical constraints on the gravitational-wave-driven r-mode instability in accreting neutron stars in low-mass x-ray binaries. We use recent results on superfluid and superconducting properties to infer the core temperature in these neutron stars and show the diversity of the observed population. Simple theoretical models indicate that many of these systems reside inside the r-mode instability region. However, this is in clear disagreement with expectations, especially for the systems containing the most rapidly rotating neutron stars. The inconsistency highlights the need to reevaluate our understanding of the many areas of physics relevant to the r-mode instability. We summarize the current status of our understanding, and we discuss directions for future research which could resolve this dilemma. PMID- 21981489 TI - f-Mode instability in relativistic neutron stars. AB - We present the first calculation of the basic properties of the f-mode instability in rapidly rotating relativistic neutron stars, adopting the Cowling approximation. By accounting for dissipation in neutron star matter, i.e., shear or bulk viscosity and superfluid mutual friction, we calculate the associated instability window. For our specific stellar model, a relativistic polytrope, we obtain a minimum gravitational growth time scale (for the dominant l=m=4 mode) of the order of 10(3)-10(4) s near the Kepler frequency Omega(K) while the instability is active above ~0.92 Omega(K) and for temperatures ~(10(9) 2*10(10)) K, characteristic of newborn neutron stars. PMID- 21981490 TI - Anisotropic N=4 super-Yang-Mills plasma and its instabilities. AB - We present a type-IIB supergravity solution dual to a spatially anisotropic finite-temperature N=4 super-Yang-Mills plasma. The solution is static and completely regular. The full geometry can be viewed as a renormalization group flow from an ultraviolet anti-de Sitter geometry to an infrared Lifshitz-like geometry. The anisotropy can be equivalently understood as resulting from a position-dependent theta term or from a nonzero number density of dissolved D7 branes. The holographic stress tensor is conserved and anisotropic. The presence of a conformal anomaly plays an important role in the thermodynamics. The phase diagram exhibits homogeneous and inhomogeneous (i.e., mixed) phases. In some regions the homogeneous phase displays instabilities reminiscent of those of weakly coupled plasmas. We comment on similarities with QCD at finite baryon density and with the phenomenon of cavitation. PMID- 21981491 TI - Holographic dual of a boundary conformal field theory. AB - We propose a holographic dual of a conformal field theory defined on a manifold with boundaries, i.e., boundary conformal field theory (BCFT). Our new holography, which may be called anti-de Sitter BCFT, successfully calculates the boundary entropy or g function in two-dimensional BCFTs and it agrees with the finite part of the holographic entanglement entropy. Moreover, we can naturally derive a holographic g theorem. We also analyze the holographic dual of an interval at finite temperature and show that there is a first order phase transition. PMID- 21981494 TI - Next-to-leading order QCD corrections to the production of two bottom-antibottom pairs at the LHC. AB - We report the results of a computation of the full next-to-leading order QCD corrections to the production of two bb pairs at the LHC. This calculation at the parton level provides predictions for well separated b jets. The results show that the next-to-leading order corrections lead to an enhancement of the cross section for the central scale choice by roughly 50% with respect to the leading order result. The theoretical uncertainty estimated by variation of the renormalization and factorization scales is strongly reduced by the inclusion of next-to-leading order corrections. PMID- 21981496 TI - New limit on time-reversal violation in beta decay. AB - We report the results of an improved determination of the triple correlation DP.(p(e)*p(v)) that can be used to limit possible time-reversal invariance in the beta decay of polarized neutrons and constrain extensions to the standard model. Our result is D=[-0.96+/-1.89(stat)+/-1.01(sys)]*10(-4). The corresponding phase between gA and gV is phiAV=180.013 degrees +/-0.028 degrees (68% confidence level). This result represents the most sensitive measurement of D in nuclear beta decay. PMID- 21981497 TI - Lifetime measurement of the 2(1)+ state in 20C. AB - Establishing how and when large N/Z values require modified or new theoretical tools is a major quest in nuclear physics. Here we report the first measurement of the lifetime of the 2(1)+ state in the near-dripline nucleus 20C. The deduced value of tau(2(1)+)=9.8+/-2.8(stat)(-1.1)(+0.5)(syst) ps gives a reduced transition probability of B(E2; 2(1)+->0(g.s.)+)=7.5(-1.7)(+3.0)(stat)( 0.4)(+1.0)(syst) e2 fm4 in good agreement with a shell model calculation using isospin-dependent effective charges. PMID- 21981499 TI - Imaging spatial correlations of Rydberg excitations in cold atom clouds. AB - We use direct spatial imaging of cold 85Rb Rydberg atom clouds to measure the Rydberg-Rydberg correlation function. The results are in qualitative agreement with theoretical predictions [F. Robicheaux and J. V. Hernandez, Phys. Rev. A 72, 063403 (2005)]. We determine the blockade radius for states 44D(5/2), 60D(5/2), and 70D(5/2) and investigate the dependence of the correlation behavior on excitation conditions and detection delay. Experimental data hint at the existence of long-range order. PMID- 21981498 TI - Direct observation of two protons in the decay of 54Zn. AB - The two protons emitted in the decay of 54Zn have been individually observed for the first time in a time projection chamber. The total decay energy and the half life measured in this work agree with the results obtained in a previous experiment. Angular and energy correlations between the two protons are determined and compared to theoretical distributions of a three-body model. Within the shell model framework, the relative decay probabilities show a strong contribution of the p2 configuration for the two-proton emission. After 45Fe, the present result on 54Zn constitutes only the second case of a direct observation of the ground state two-proton decay of a long-lived isotope. PMID- 21981500 TI - Direct measurement of the free cyclotron frequency of a single particle in a Penning trap. AB - A measurement scheme for the direct determination of the free cyclotron frequency nu(c) of a single particle stored in a Penning trap is described. The method is based on the dressed states of mode coupling. In this novel measurement scheme both radial modes of the single trapped particle are simultaneously coupled to the axial oscillation mode. PMID- 21981501 TI - Multimode vibrational couplings in resonant positron annihilation. AB - The mechanisms for multimode vibrational couplings in resonant positron annihilation are not well understood. We show that these resonances can arise from positron-induced distortions of the potential energy surface (target response to the positron field). Though these distortions can transfer energy into single- and multiquantum vibrations, they have so far been disregarded as a pathway to resonant annihilation. We also compare the existing annihilation theories and show that the currently accepted model can be cast as a special case of the Feshbach annihilation theory. PMID- 21981502 TI - Classical analogue of displaced Fock states and quantum correlations in Glauber Fock photonic lattices. AB - Coherent states and their generalizations, displaced Fock states, are of fundamental importance to quantum optics. Here we present a direct observation of a classical analogue for the emergence of these states from the eigenstates of the harmonic oscillator. To this end, the light propagation in a Glauber-Fock waveguide lattice serves as equivalent for the displacement of Fock states in phase space. Theoretical calculations and analogue classical experiments show that the square-root distribution of the coupling parameter in such lattices supports a new family of intriguing quantum correlations not encountered in uniform arrays. Because of the broken shift invariance of the lattice, these correlations strongly depend on the transverse position. Consequently, quantum random walks with this extra degree of freedom may be realized in Glauber-Fock lattices. PMID- 21981503 TI - Optical nonlinearity in Ar and N2 near the ionization threshold. AB - We directly measure the nonlinear optical response in argon and nitrogen in a thin gas target to laser intensities near the ionization threshold. No instantaneous negative nonlinear refractive index is observed, nor is saturation, in contrast with a previous measurement [Opt. Express 17, 13429 (2009)] and calculations [Phys. Rev. Lett. 106, 183902 (2011)]. In addition, we are able to cleanly separate the instantaneous and rotational components of the nonlinear response in nitrogen. In both Ar and N2, the peak instantaneous index response scales linearly with the laser intensity until the point of ionization, whereupon the response turns abruptly negative and ~constant, consistent with plasma generation. PMID- 21981504 TI - p-Wave cold collisions in an optical lattice clock. AB - We study ultracold collisions in fermionic ytterbium by precisely measuring the energy shifts they impart on the atoms' internal clock states. Exploiting Fermi statistics, we uncover p-wave collisions, in both weakly and strongly interacting regimes. With the higher density afforded by two-dimensional lattice confinement, we demonstrate that strong interactions can lead to a novel suppression of this collision shift. In addition to reducing the systematic errors of lattice clocks, this work has application to quantum information and quantum simulation with alkaline-earth atoms. PMID- 21981505 TI - Resonance assisted synchronization of coupled oscillators: frequency locking without phase locking. AB - Frequency locking without phase locking of two coupled nonlinear oscillators is experimentally demonstrated. This synchronization regime is found for two coupled laser modes, beyond the phase-locking range fixed by Adler's equation, because of a resonance mechanism. Specifically, we show that the amplitudes of the two modes exhibit strong fluctuations that produce average frequency synchronization, even if the instantaneous phases are unlocked. The experimental results are in good agreement with a theoretical model. PMID- 21981506 TI - Ion temperature and hydrodynamic-energy measurements in a Z-pinch plasma at stagnation. AB - The time history of the local ion kinetic energy in a stagnating plasma was determined from Doppler-dominated line shapes. Using independent determination of the plasma properties for the same plasma region, the data allowed for inferring the time-dependent ion temperature, and for discriminating the temperature from the total ion kinetic energy. It is found that throughout most of the stagnation period the ion thermal energy constitutes a small fraction of the total ion kinetic energy; the latter is dominated by hydrodynamic motion. Both the ion hydrodynamic and thermal energies are observed to decrease to the electron thermal energy by the end of the stagnation period. It is confirmed that the total ion kinetic energy available at the stagnating plasma and the total radiation emitted are in balance, as obtained in our previous experiment. The dissipation time of the hydrodynamic energy thus appears to determine the duration (and power) of the K emission. PMID- 21981493 TI - Observation of the Xi(b)(0) baryon. AB - The observation of the bottom, strange baryon Xi(b)(0) through the decay chain Xi(b)(0)->Xi(c)(+)pi-, where XiXi(c)(+)->Xi- pi+ pi+, Xi-->Lambdapi-, and Lambda >ppi-, is reported by using data corresponding to an integrated luminosity of 4.2 fb(-1) from pp collisions at square root(s)=1.96 TeV recorded with the Collider Detector at Fermilab. A signal of 25.3(-5.4)(+5.6) candidates is observed whose probability of arising from a background fluctuation is 3.6*10(-12), corresponding to 6.8 gaussian standard deviations. The Xi(b)(0) mass is measured to be 5787.8+/-5.0(stat)+/-1.3(syst) MeV/c2. In addition, the Xi(b)- baryon is observed through the process Xi(b)-->Xi(c)(0)pi-, where Xi(c)(0)->Xi- pi+, Xi- >Lambdapi-, and Lambda->ppi-. PMID- 21981507 TI - Production of picosecond, kilojoule, and petawatt laser pulses via Raman amplification of nanosecond pulses. AB - Raman amplification in plasma has been promoted as a means of compressing picosecond optical laser pulses to femtosecond duration to explore the intensity frontier. Here we show for the first time that it can be used, with equal success, to compress laser pulses from nanosecond to picosecond duration. Simulations show up to 60% energy transfer from pump pulse to probe pulse, implying that multikilojoule ultraviolet petawatt laser pulses can be produced using this scheme. This has important consequences for the demonstration of fast ignition inertial confinement fusion. PMID- 21981509 TI - Thermal-induced edge barriers and forces in interlayer interaction of concentric carbon nanotubes. AB - Molecular dynamics simulations reveal that thermal-induced edge barriers and forces can govern the interlayer interaction of double walled carbon nanotubes. As a result, friction in such systems depends on both the area of contact and the length of the contact edges. The latter effect is negligible in macroscopic friction and provides a feasible explanation for the seemingly contradictory laws of interlayer friction, which have been reported in the literature. The temperature-dependent edge forces can be utilized as a driving force in carbon nanotube thermal actuators, and has general implications for nanoscale friction and contact. PMID- 21981508 TI - Dynamic evanescent phonon coupling across the La(1-x)Sr(x)MnO3/SrTiO3 interface. AB - The transport and magnetic properties of correlated La0.53Sr0.47MnO3 ultrathin films, grown epitaxially on SrTiO3, show a sharp cusp at the structural transition temperature of the substrate. Using a combination of experiment and first principles theory we show that the cusp is a result of evanescent cross interface coupling between the charge carriers in the film and a soft phonon mode in the SrTiO3, mediated through linked oxygen octahedral motions. The amplitude of the mode diverges at the transition temperature, and phonons are launched into the first few atomic layers of the film, affecting its electronic state. PMID- 21981510 TI - Structural transitions of solvent-free oligomer-grafted nanoparticles. AB - Novel structural transitions of solvent-free oligomer-grafted nanoparticles are investigated by using molecular dynamics simulations of a coarse-grained bead spring model. Variations in core size and grafting density lead to self-assembly of the nanoparticles into a variety of distinct structures. At the boundaries between different structures, the nanoparticle systems undergo thermoreversible transitions. This structural behavior, which has not been previously reported, deviates significantly from that of simple liquids. The reversible nature of these transitions in solvent-free conditions offers new ways to control self assembly of nanoparticles at experimentally accessible conditions. PMID- 21981511 TI - Identification of strong and weak interacting two-level systems in KBr:CN. AB - Tunneling two-level systems (TLSs) are believed to be the source of phenomena such as the universal low temperature properties in disordered and amorphous solids, and 1/f noise. The existence of these phenomena in a large variety of dissimilar physical systems testifies for the universal nature of the TLSs, which however, is not yet known. Following a recent suggestion that attributes the low temperature TLSs to inversion pairs [M. Schechter and P. C. E. Stamp, arXiv:0910.1283.] we calculate explicitly the TLS-phonon coupling of inversion symmetric and asymmetric TLSs in a given disordered crystal. Our work (a) estimates parameters that support the theory in M. Schechter and P. C. E. Stamp, arXiv:0910.1283, in its general form, and (b) positively identifies, for the first time, the relevant TLSs in a given system. PMID- 21981512 TI - Emergence of long-range correlations and rigidity at the dynamic glass transition. AB - At the so-called dynamic glass transition predicted by the mean-field replica approach equilibrium liquid's translational symmetry is spontaneously broken, albeit at the microscopic level. We show that this fact implies the emergence of Goldstone modes and long-range density correlations. We derive and evaluate a new statistical mechanical expression for the glass shear modulus. PMID- 21981513 TI - Elastic metamaterials with simultaneously negative effective shear modulus and mass density. AB - We propose a type of elastic metamaterial comprising fluid-solid composite inclusions which can possess a negative shear modulus and negative mass density over a large frequency region. Such a material has the unique property that only transverse waves can propagate with a negative dispersion while longitudinal waves are forbidden. This leads to many interesting phenomena such as negative refraction, which is demonstrated by using a wedge sample and a significant amount of mode conversion from transverse waves to longitudinal waves that cannot occur on the interface of two natural solids. PMID- 21981514 TI - Slow aging dynamics and avalanches in a gold-cadmium alloy investigated by x-ray photon correlation spectroscopy. AB - Results of a x-ray photon correlation spectroscopy experiment on the very weakly first order martensitic transformation of a Au50.5Cd49.5 single crystal are presented. Slow non-equilibrium-dynamics are observed in a narrow temperature interval in the direct vicinity of the otherwise athermal phase transformation. These dynamics are associated with the martensite-aging effect. The dynamical aging is accompanied by an avalanchelike behavior which is identified with an incubation-time phenomenon. PMID- 21981515 TI - Spontaneous pattern formation in a polariton condensate. AB - Exciton-polariton condensation can be regarded as a self-organization phenomenon, where phase ordering is established among particles in the system. In such condensed systems, further ordering can occur in the particle density distribution, under particular experimental conditions. In this work we report on spontaneous pattern formation in a polariton condensate under nonresonant optical pumping. The slightly elliptical ring-shaped excitation laser that we employ forces condensation to occur into a single-energy state with periodic boundary conditions, giving rise to a multilobe standing-wave patterned state. PMID- 21981516 TI - Topological Fermi liquids from Coulomb interactions in the doped honeycomb lattice. AB - We propose a simple method for obtaining time reversal symmetry (T) broken phases in simple lattice models based on enlarging the unit cell. As an example we study the honeycomb lattice with nearest neighbor hopping and a local nearest neighbor Coulomb interaction V. We show that when the unit cell is enlarged to host six atoms that permits Kekule distortions, self-consistent currents spontaneously form creating nontrivial magnetic configurations with total zero flux at high electron densities. A very rich phase diagram is obtained within a variational mean field approach that includes metallic phases with broken time reversal symmetry (T). The predominant (T) breaking configuration is an anomalous Hall phase, a realization of a topological Fermi liquid. PMID- 21981495 TI - Measurement of the cross section for prompt isolated diphoton production in pp collisions at square root(s) = 1.96 TeV. AB - This Letter reports a measurement of the cross section of prompt isolated photon pair production in pp collisions at a total energy square root(s)=1.96 TeV using data of 5.36 fb(-1) integrated luminosity collected with the CDF II detector at the Fermilab Tevatron. The measured cross section, differential in basic kinematic variables, is compared with three perturbative QCD predictions, a leading order parton shower calculation and two next-to-leading order calculations. The next-to-leading order calculations reproduce most aspects of the data. By including photon radiation from quarks before and after hard scattering, the parton shower prediction becomes competitive with the next-to leading order predictions. PMID- 21981517 TI - Ab initio theory of the scattering-independent anomalous Hall effect. AB - We report on first-principles calculations of the side-jump contribution to the anomalous Hall conductivity (AHC) directly from the electronic structure of a perfect crystal. We implemented our approach for a short-range scattering disorder model within the density functional theory and computed the full scattering-independent AHC in elemental bcc Fe, hcp Co, fcc Ni, and L1(0) FePd and FePt alloys. The full AHC thus calculated agrees systematically with experiment to a degree unattainable so far, correctly capturing the previously missing elements of side-jump contributions, hence paving the way to a truly predictive theory of the anomalous Hall effect and turning it from a characterization tool to a probing tool of multiband complex electronic band structures. PMID- 21981519 TI - Dissipationless electron transport in photon-dressed nanostructures. AB - It is shown that the electron coupling to photons in field-dressed nanostructures can result in the ground electron-photon state with a nonzero electric current. Since the current is associated with the ground state, it flows without the Joule heating of the nanostructure and is nondissipative. Such a dissipationless electron transport can be realized in strongly coupled electron-photon systems with the broken time-reversal symmetry--particularly, in quantum rings and chiral nanostructures dressed by circularly polarized photons. PMID- 21981518 TI - Fermi surface and superconductivity in low-density high-mobility delta-doped SrTiO3. AB - The electronic structure of low-density n-type SrTiO3 delta-doped heterostructures is investigated by angular dependent Shubnikov-de Haas oscillations. In addition to a controllable crossover from a three- to two dimensional Fermi surface, clear beating patterns for decreasing dopant layer thicknesses are found. These indicate the lifting of the degeneracy of the conduction band due to subband quantization in the two-dimensional limit. Analysis of the temperature-dependent oscillations shows that similar effective masses are found for all components, associated with the splitting of the light electron pocket. The dimensionality crossover in the superconducting state is found to be distinct from the normal state, resulting in a rich phase diagram as a function of dopant layer thickness. PMID- 21981520 TI - Equality of bulk wave functions and edge correlations in some topological superconductors: a spacetime derivation. AB - For certain systems, the N-particle ground-state wave functions of the bulk happen to be exactly equal to the N-point spacetime correlation functions at the edge, in the infrared limit. We show why this had to be so for a class of topological superconductors, beginning with the p+ip state in D=2+1. Varying the chemical potential as a function of Euclidean time between weak and strong pairing states is shown to extract the wave function. Then a Euclidean rotation that exchanges time and space and approximate Lorentz invariance lead to the edge connection. This framework readily generalizes to other dimensions. We illustrate it with a D=3+1 example, superfluid 3He- B, and a p-wave superfluid in D=1+1. Our method works only when the particle number is not conserved, as in superconductors. PMID- 21981521 TI - Two-site Kondo effect in atomic chains. AB - Linear CoCu(n)Co clusters on Cu(111) fabricated by atomic manipulation represent a two-site Kondo system with tunable interaction. Scanning tunneling spectroscopy reveals oscillations of the Kondo temperature T(K) with the number n of Cu atoms for n>=3. Density functional calculations show that the Ruderman-Kittel-Kasuya Yosida interaction mediated by the Cu chains causes the oscillations. Calculations find ferromagnetic and antiferromagnetic interaction for n=1 and 2, respectively. Both interactions lead to a decrease of T(K) as experimentally observed. PMID- 21981522 TI - Absence of spontaneous magnetic order of lattice spins coupled to itinerant interacting electrons in one and two dimensions. AB - We extend the Mermin-Wagner theorem to a system of lattice spins which are spin coupled to itinerant and interacting charge carriers. We use the Bogoliubov inequality to rigorously prove that neither (anti-) ferromagnetic nor helical long-range order is possible in one and two dimensions at any finite temperature. Our proof applies to a wide class of models including any form of electron electron and single-electron interactions that are independent of spin. In the presence of Rashba or Dresselhaus spin-orbit interactions (SOI) magnetic order is not excluded and intimately connected to equilibrium spin currents. However, in the special case when Rashba and Dresselhaus SOIs are tuned to be equal, magnetic order is excluded again. This opens up a new possibility to control magnetism electrically. PMID- 21981523 TI - Proximity effects of a symmetry-breaking interface on spins of photoexcited electrons. AB - We study reflection of optically spin-oriented hot electrons as a means to probe the semiconductor crystal symmetry and its intimate relation with the spin-orbit coupling. The symmetry breaking by reflection manifests itself by tipping the net spin vector of the photoexcited electrons out of the light propagation direction. The tipping angle and the pointing direction of the net-spin vector are set by the crystal-induced spin precession, momentum alignment, and spin-momentum correlation of the initial photoexcited electron population. We examine nonmagnetic semiconductor heterostructures and semiconductor-ferromagnet systems and show the unique signatures of these effects. PMID- 21981524 TI - Spin-orbit symmetries of conduction electrons in silicon. AB - We derive a spin-dependent Hamiltonian that captures the symmetry of the zone edge states in silicon. We present analytical expressions of the spin-dependent states and of spin relaxation due to electron-phonon interactions in the multivalley conduction band. We find excellent agreement with experimental results. Similar to the usage of the Kane Hamiltonian in direct band-gap semiconductors, the new Hamiltonian can be used to study spin properties of electrons in silicon. PMID- 21981525 TI - Control of magnetic fluctuations by spin current. AB - We use microfocus Brillouin light scattering spectroscopy to study the interaction of spin current with magnetic fluctuations in a Permalloy microdisk located on top of a Pt strip carrying an electric current. We show that the fluctuations can be efficiently suppressed or enhanced by different directions of the electric current. Additionally, we find that the effect of spin current on magnetic fluctuations is strongly influenced by nonlinear magnon-magnon interactions. The observed phenomena can be used for controllable reduction of thermal noise in spintronic nanodevices. PMID- 21981526 TI - Effective mass anisotropy of hot electrons in nonparabolic conduction bands of n doped InGaAs films using ultrafast terahertz pump-probe techniques. AB - The anisotropic effective mass of energetic electrons in an isotropic, nonparabolic conduction band is revealed using ultrafast THz-pump-THz-probe techniques in a n-doped InGaAs semiconductor thin film. A microscopic theory is applied to identify the origin of the observed anisotropy and to show that the self-consistent light-matter coupling contributes significantly to the THz response. PMID- 21981527 TI - Two-spinon and orbital excitations of the spin-Peierls system TiOCl. AB - We combine high-resolution resonant inelastic x-ray scattering with cluster calculations utilizing a recently derived effective magnetic scattering operator to analyze the polarization, excitation energy, and momentum-dependent excitation spectrum of the low-dimensional quantum magnet TiOCl in the range expected for orbital and magnetic excitations (0-2.5 eV). Ti 3d orbital excitations yield complete information on the temperature-dependent crystal-field splitting. In the spin-Peierls phase we observe a dispersive two-spinon excitation and estimate the inter- and intradimer magnetic exchange coupling from a comparison to cluster calculations. PMID- 21981528 TI - Extended phonon collapse and the origin of the charge-density wave in 2H-NbSe2. AB - We report inelastic x-ray scattering measurements of the temperature dependence of phonon dispersion in the prototypical charge-density-wave (CDW) compound 2H NbSe2. Surprisingly, acoustic phonons soften to zero frequency and become overdamped over an extended region around the CDW wave vector. This extended phonon collapse is dramatically different from the sharp cusp in the phonon dispersion expected from Fermi surface nesting. Instead, our experiments, combined with ab initio calculations, show that it is the wave vector dependence of the electron-phonon coupling that drives the CDW formation in 2H-NbSe2 and determines its periodicity. This mechanism explains the so far enigmatic behavior of CDW in 2H-NbSe2 and may provide a new approach to other strongly correlated systems where electron-phonon coupling is important. PMID- 21981529 TI - Near-zero-field nuclear magnetic resonance. AB - We investigate nuclear magnetic resonance (NMR) in near zero field, where the Zeeman interaction can be treated as a perturbation to the electron mediated scalar interaction (J coupling). This is in stark contrast to the high-field case, where heteronuclear J couplings are normally treated as a small perturbation. We show that the presence of very small magnetic fields results in splitting of the zero-field NMR lines, imparting considerable additional information to the pure zero-field spectra. Experimental results are in good agreement with first-order perturbation theory and with full numerical simulation when perturbation theory breaks down. We present simple rules for understanding the splitting patterns in near-zero-field NMR, which can be applied to molecules with nontrivial spectra. PMID- 21981530 TI - 2D atomic mapping of oxidation states in transition metal oxides by scanning transmission electron microscopy and electron energy-loss spectroscopy. AB - Using a combination of high-angle annular dark-field scanning transmission electron microscopy and atomically resolved electron energy-loss spectroscopy in an aberration-corrected transmission electron microscope we demonstrate the possibility of 2D atom by atom valence mapping in the mixed valence compound Mn3O4. The Mn L(2,3) energy-loss near-edge structures from Mn2+ and Mn3+ cation sites are similar to those of MnO and Mn2O3 references. Comparison with simulations shows that even though a local interpretation is valid here, intermixing of the inelastic signal plays a significant role. This type of experiment should be applicable to challenging topics in materials science, such as the investigation of charge ordering or single atom column oxidation states in, e.g., dislocations. PMID- 21981531 TI - Weak and strong coupling theories for polarizable colloids and nanoparticles. AB - A theory is presented which allows us to accurately calculate the density profile of monovalent and multivalent counterions in suspensions of polarizable colloids or nanoparticles. In the case of monovalent ions, we derive a weak-coupling theory that explicitly accounts for the ion-image interaction, leading to a modified Poisson-Boltzmann equation. For suspensions with multivalent counterions, a strong-coupling theory is used to calculate the density profile near the colloidal surface and a Poisson-Boltzmann equation with a renormalized boundary condition to account for the counterion distribution in the far field. All the results are compared with the Monte Carlo simulations, showing an excellent agreement between the theory and the simulations. PMID- 21981532 TI - Numerical simulation of the sedimentation of a sphere in a sheared granular fluid: a granular Stokes experiment. AB - We study, computationally, the sedimentation of a sphere of higher mass in a steady, gravity-driven granular flow of otherwise identical spheres, on a rough inclined plane. Taking a hydrodynamic approach at the scale of the particle, we find the drag force to be given by a modified Stokes law and the buoyancy force by the Archimedes principle, with excluded volume effects taken into account. We also find significant differences between the hydrodynamic case and the granular case, which are highlighted. PMID- 21981533 TI - Accurate eikonal-curvature relation for wave fronts in locally anisotropic reaction-diffusion systems. AB - The dependency of wave velocity in reaction-diffusion (RD) systems on the local front curvature determines not only the stability of wave propagation, but also the fundamental properties of other spatial configurations such as vortices. This Letter gives the first derivation of a covariant eikonal-curvature relation applicable to general RD systems with spatially varying anisotropic diffusion properties, such as cardiac tissue. The theoretical prediction that waves which seem planar can nevertheless possess a nonvanishing geometrical curvature induced by local anisotropy is confirmed by numerical simulations, which reveal deviations up to 20% from the nominal plane wave speed. PMID- 21981534 TI - Underwound DNA under tension: structure, elasticity, and sequence-dependent behaviors. AB - DNA melting under torsion plays an important role in a wide variety of cellular processes. In the present Letter, we have investigated DNA melting at the single molecule level using an angular optical trap. By directly measuring force, extension, torque, and angle of DNA, we determined the structural and elastic parameters of torsionally melted DNA. Our data reveal that under moderate forces, the melted DNA assumes a left-handed structure as opposed to an open bubble conformation and is highly torsionally compliant. We have also discovered that at low forces melted DNA properties are highly dependent on DNA sequence. These results provide a more comprehensive picture of the global DNA force-torque phase diagram. PMID- 21981535 TI - Regularity of spike trains and harmony perception in a model of the auditory system. AB - Spike train regularity of the noisy neural auditory system model under the influence of two sinusoidal signals with different frequencies is investigated. For the increasing ratio m/n of the input signal frequencies (m, n are natural numbers) the linear growth of the regularity is found at the fixed difference (m n). It is shown that the spike train regularity in the model is high for harmonious chords of input tones and low for dissonant ones. PMID- 21981536 TI - Measurement of correlations between low-frequency vibrational modes and particle rearrangements in quasi-two-dimensional colloidal glasses. AB - We investigate correlations between low-frequency vibrational modes and rearrangements in two-dimensional colloidal glasses composed of thermosensitive microgel particles, which readily permit variation of the sample packing fraction. At each packing fraction, the particle displacement covariance matrix is measured and used to extract the vibrational spectrum of the "shadow" colloidal glass (i.e., the particle network with the same geometry and interactions as the sample colloid but absent damping). Rearrangements are induced by successive, small reductions in the packing fraction. The experimental results suggest that low-frequency quasilocalized phonon modes in colloidal glasses, i.e., modes that present low energy barriers for system rearrangements, are spatially correlated with rearrangements in this thermal system. PMID- 21981537 TI - Vibrational modes identify soft spots in a sheared disordered packing. AB - We analyze low-frequency vibrational modes in a two-dimensional, zero temperature, quasistatically sheared model glass to identify a population of structural "soft spots" where particle rearrangements are initiated. The population of spots evolves slowly compared to the interval between particle rearrangements, and the soft spots are structurally different from the rest of the system. Our results suggest that disordered solids flow via localized rearrangements that tend to occur at soft spots, which are analogous to dislocations in crystalline solids. PMID- 21981538 TI - Jamming, yielding, and rheology of weakly vibrated granular media. AB - We establish that the rheological curve of dry granular media is nonmonotonic, both in the presence and absence of external mechanical agitations. In the presence of weak vibrations, the nonmonotonic flow curves govern a hysteretic transition between slow but steady and fast, inertial flows. In the absence of vibrations, the nonmonotonic flow curve governs the yielding behavior of granular media. Finally, we show that nonmonotonic flow curves can be seen in at least two different flow geometries and for several granular materials. PMID- 21981539 TI - Influence and dynamic behavior in random boolean networks. AB - We present a rigorous mathematical framework for analyzing dynamics of a broad class of boolean network models. We use this framework to provide the first formal proof of many of the standard critical transition results in boolean network analysis, and offer analogous characterizations for novel classes of random boolean networks. We show that some of the assumptions traditionally made in the more common mean-field analysis of boolean networks do not hold in general. For example, we offer evidence that imbalance (internal inhomogeneity) of transfer functions is a crucial feature that tends to drive quiescent behavior far more strongly than previously observed. PMID- 21981540 TI - Noncooperatively optimized tolerance: decentralized strategic optimization in complex systems. AB - We introduce noncooperatively optimized tolerance (NOT), a game theoretic generalization of highly optimized tolerance (HOT), which we illustrate in the forest fire framework. As the number of players increases, NOT retains features of HOT, such as robustness and self-dissimilar landscapes, but also develops features of self-organized criticality. The system retains considerable robustness even as it becomes fractured, due in part to emergent cooperation between players, and at the same time exhibits increasing resilience against changes in the environment, giving rise to intermediate regimes where the system is robust to a particular distribution of adverse events, yet not very fragile to changes. PMID- 21981541 TI - Comment on "Raman scattering study of phase biaxiality in a thermotropic bent core nematic liquid crystal". PMID- 21981543 TI - Interdonation intervals and patterns of return among blood donors in Brazil. AB - BACKGROUND: In Brazil, most donations come from repeat donors, but there are little data on return behavior of donors. STUDY DESIGN AND METHODS: Donors who made at least one whole blood donation in 2007 were followed for 2 years using a large multicenter research database. Donation frequency, interdonation intervals, and their association with donor demographics, status, and type of donation were examined among three large blood centers in Brazil, two in the southeast and one in the northeast. RESULTS: In 2007, of 306,770 allogeneic donations, 38.9% came from 95,127 first-time donors and 61.1% from 149,664 repeat donors. Through December 31, 2009, a total of 28.1% of first-time donors and 56.5% of repeat donors had donated again. Overall, the median interdonation interval was approximately 6 months. Among men it was 182 and 171 days for first-time and repeat donors, and among women, 212 and 200 days. Predictors of return behavior among first-time donors were male sex (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.13-1.20), community donation (OR, 2.26; 95% CI, 2.20-2.33), and age 24 years or less (OR, 0.62-0.89 for donors >= 25 years). Among repeat donors predictors were male sex (OR, 1.35; 95% CI, 1.32-1.39), age 35 years or more (OR, 1.08-1.18 vs. <= 24 years), and community donation (OR, 2.39; 95% CI, 2.33-2.44). Differences in return by geographic region were evident with higher return rates in the northeast of Brazil. CONCLUSION: These data highlight the need to develop improved communication strategies for first-time and replacement donors to convert them into repeat community donors. PMID- 21981544 TI - Replacement of fish meal protein by surimi by-product protein in the diet of blue gourami Trichogaster trichopterus fingerlings. AB - Based on the nutrient requirement of Trichogaster trichopterus, a fish meal-based basal diet with 350 g/kg diet crude protein and 16.7 MJ/kg energy was formulated, in which the fish meal protein was replaced by surimi by-product protein at 0.0 (control), 12.5, 25, 50, 75 and 100% levels. The formulated diets were fed ad libitum to T. trichopterus fingerlings (4.80 +/- 0.03 g) in triplicate groups for 45 days in a closed water system. Eighteen fibre-reinforced plastic tanks with 200 l of water were used for rearing the fish. Weight gain, specific growth rate, feed/gain ratio, protein efficiency ratio, nutrient retention and digestibility (protein and energy) of fish were not affected (p > 0.05) up to 50% fish meal protein replacement level by surimi by-product protein. While whole-body protein content of fish was marginally decreased, the lipid content was increased with increase in surumi by-product incorporation level in the diet. The study results suggest that the fish meal protein, which is scarce and costly nowadays, could be replaced up to 50% by surimi by-product protein in the diet of blue gourami without hampering the growth and nutrient utilization of fish. PMID- 21981545 TI - Migraine--more than a headache: women's experiences of living with migraine. AB - PURPOSE: In this qualitative study the aim was to explore the meaning of living with migraine. METHODS: In-depth interviews were conducted with ten women about their experience of living with migraine. Halfway through the interview, the women drew a picture of what living with migraine is like, and the interview continued with the conversation being guided by the picture. The interviews were analyzed using a hermeneutic phenomenological method inspired by van Manen. RESULTS: The analysis revealed an essence "Being obliged to endure a life accompanied by an unpredictable and invisible disorder" and three themes "Being besieged by an attack", "Struggling in a life characterized by uncertainty" and "Living with an invisible disorder." CONCLUSIONS: Migraine is a debilitating disorder which accompanies life in the sense that it or the threat of its return is always present, and yet invisible to others. The struggle of enduring life with migraine is worsened by the feeling of having an invisible disorder and of being doubted. There is a need to increase the knowledge among healthcare professionals about what it means to live with migraine, something this qualitative study offers. PMID- 21981546 TI - Modulation of the cytokine response in human monocytes by mycobacterium leprae phenolic glycolipid-1. AB - Leprosy is a chronic but treatable infectious disease caused by the intracellular pathogen Mycobacterium leprae. M. leprae cell wall is characterized by a unique phenolic glycolipid-1 (PGL-1) reported to have several immune functions. We have examined the role of PGL-1 in the modulation of monocyte cytokine/chemokine production in naive human monocytes. PGL-1 in its purified form or expressed in a recombinant Mycobacterium bovis Bacillus Colmette-Guerin (BCG) background (rBCG PGL-1) was tested. We found that PGL-1 selectively modulated the induction of specific monocyte cytokines and chemokines and, when used as prestimulus, exerted priming and/or inhibitory effects on the induction of selected cytokines/chemokines in response to a second stimulus. Taken together, the results of this study support a modulatory role for PGL-1 in the innate immune response to M. leprae. Thus, PGL-1 may play an important role in the development of the anergic clinical forms of disease and in tissue damage seen in lepromatous patients and during the reactional states of leprosy. PMID- 21981547 TI - DNMT3A mutations are rare in childhood acute myeloid leukaemia, myelodysplastic syndromes and juvenile myelomonocytic leukaemia. PMID- 21981548 TI - Applying medicinal chemistry transformations and multiparameter optimization to guide the search for high-quality leads and candidates. AB - In this article we describe a computational method that automatically generates chemically relevant compound ideas from an initial molecule, closely integrated with in silico models, and a probabilistic scoring algorithm to highlight the compound ideas most likely to satisfy a user-defined profile of required properties. The new compound ideas are generated using medicinal chemistry 'transformation rules' taken from examples in the literature. We demonstrate that the set of 206 transformations employed is generally applicable, produces a wide range of new compounds, and is representative of the types of modifications previously made to move from lead-like to drug-like compounds. Furthermore, we show that more than 94% of the compounds generated by transformation of typical drug-like molecules are acceptable to experienced medicinal chemists. Finally, we illustrate an application of our approach to the lead that ultimately led to the discovery of duloxetine, a marketed serotonin reuptake inhibitor. PMID- 21981549 TI - Chip-type asymmetrical flow field-flow fractionation channel coupled with mass spectrometry for top-down protein identification. AB - A chip-type design asymmetrical flow field-flow fractionation (AF4) channel has been developed for high-speed separation of proteins and top-down proteomic analysis using online coupled electrospray ionization mass spectrometry (ESI-MS). The new miniaturized AF4 channel was assembled by stacking multilayer thin stainless steel (SS, 1.5 mm each) plates embedded with an SS frit in such a way that the total thickness of the channel assembly was about 6 mm. The efficiency of the miniaturized AF4 channel at different channel lengths was examined with the separation of protein standards by adjusting flow rates in which an identical effective channel flow rate or an identical void time can be maintained at different channels. Detection limit, overloading effect, reproducibility, and influence of channel membrane materials on separation efficiency were investigated. Desalting and purification of proteins achieved during the AF4 operation by the action of an exiting crossflow and the use of aqueous mass spectrometry-compatible (MS-compatible) buffer were advantageous for online coupling of the chip-type AF4 with ESI-MS. The direct coupling of AF4 and ESI-MS capabilities was demonstrated for the high-speed separation and identification of carbonic anhydrase (29 kDa) and transferrin (78 kDa) by full scan MS and for the first top-down identification of proteins with AF4-ESI-MS-MS using collision induced fragmentation (CID). The presence of intact dimers (156 kDa) of transferrin was confirmed by AF4-ESI-MS via size separation of the dimers from monomers, followed by multiply charged ion spectral analysis of the dimers and molecular mass determinations. It was also found from these experiments that AF4 ESI-MS analysis of transferrin exhibited an increased signal-to-noise ratio compared to that of direct ESI-MS analysis due to online purification of the protein sample and size separation of dimers with AF4. PMID- 21981550 TI - Effect of the beta-propiolactone treatment on the adsorption and fusion of influenza A/Brisbane/59/2007 and A/New Caledonia/20/1999 virus H1N1 on a dimyristoylphosphatidylcholine/ganglioside GM3 mixed phospholipids monolayer at the air-water interface. AB - The production protocol of many whole cell/virion vaccines involves an inactivation step with beta-propiolactone (BPL). Despite the widespread use of BPL, its mechanism of action is poorly understood. Earlier work demonstrated that BPL alkylates nucleotide bases, but its interaction with proteins has not been studied in depth. In the present study we use ellipsometry to analyze the influence of BPL treatment of two H1N1 influenza strains, A/Brisbane/59/2007 and A/New Caledonia/20/1999, which are used for vaccine production on an industrial scale. Analyses were conducted using a mixed lipid monolayer containing ganglioside GM3, which functions as the viral receptor. Our results show that BPL treatment of both strains reduces viral affinity for the mixed monolayer and also diminishes the capacity of viral domains to self-assemble. In another series of experiments, the pH of the subphase was reduced from 7.4 to 5 to provoke the pH induced conformational change of hemagglutinin, which occurs following endocytosis into the endosome. In the presence of the native virus the pH decrease caused a reduction in domain size, whereas lipid layer thickness and surface pressure were increased. These observations are consistent with a fusion of the viral membrane with the lipid monolayer. Importantly, this fusion was not observed with adsorbed inactivated virus, which indicates that BPL treatment inhibits the first step of virus-membrane fusion. Our data also indicate that BPL chemically modifies hemagglutinin, which mediates the interaction with GM3. PMID- 21981551 TI - Establishment of the genetic/genomic competency center for education. AB - PURPOSE: Develop a trans-disciplinary repository of genomics education resources using a Web-based learning management system. The repository maps and organizes genetic-genomic information and materials relevant to educators by healthcare discipline-specific competencies and performance indicators. METHODS: An interdisciplinary project team was established to guide toolkit repository building and usability testing. The toolkit was built using the X-CREDIT software on the Moodle learning management platform, which includes a mapping matrix and browsing function that captures teaching resources in a searchable database linked to competencies, knowledge areas, performance indicators, learning activities and resources, and outcome assessments. Discipline-specific advisory groups assisted in resource identification, competency mapping, and peer review. The toolkit is multidisciplinary, currently including physician assistants and nurses, and provides a resource crosslink to discipline-specific competencies. All resources have a detailed description, and users may contribute new resources, which are peer reviewed for relevance and accuracy by an editorial board. Alpha and beta testing using online usability surveys that included toolkit exercises helped refine the structure, look, and navigation of the final website. FINDINGS: One hundred thirty faculty-124 nursing and 6 physician assistant faculty-agreed to participate. Of those, 59 users (45.4% response rate) completed the online usability survey. Nearly all users (94.9%) were able to find a competency that was relevant to their topic, and 85.4% were able to locate the relevant performance indicators. The majority (86.5%) felt the model adequately described the relationships between competencies, performance indicators, learning activities-resources, and assessments, and made conceptual sense. Survey respondents reported font color and size made the information difficult to read, windows were not large enough, and the "shopping cart" concept was confusing; all of these areas have been modified for the final toolkit version. CONCLUSIONS: Alpha and beta testing of the toolkit revealed that users can successfully obtain educational materials by searching competencies and performance indicators. The platform is accessible on the Internet at http://www.g-2-c-2.org and can be continually updated as new resources become available. CLINICAL RELEVANCE: Faculty members need easy access to a wide range of accurate, current resources to facilitate integration of genomics into the curriculum. PMID- 21981552 TI - No evidence of association between 8q24 and susceptibility to nonsyndromic cleft lip with or without palate in Japanese population. AB - OBJECTIVE: Recent genome-wide association studies identified susceptibility loci for nonsyndromic cleft lip with or without cleft palate (NSCL+/-P) on 8q24.21, 10q25.3, 13q31.1, 15q13.3, 17q22, and 18q22 in populations of European origin. The purpose of this study was to determine, using DNA samples, whether 8q24.21 was a susceptibility locus for the development of NSCL+/-P in Japanese patients. METHODS: We used DNA from 167 Japanese NSCL+/-P patients (45 cleft lip without cleft palate and 122 cleft lip with cleft palate patients) and 190 Japanese unaffected control individuals. We performed an association study using 13 single nucleotide polymorphisms (SNPs) selected on the 8q24.21 locus. Genotyping of each SNP was carried out by direct sequencing of genomic DNA. Additionally, a haplotype block was constructed using the selected SNPs. RESULTS: The 13 selected SNPs were successfully genotyped in 357 individuals. The p values obtained were not low enough to indicate a significant association between the haplotypes and the development of NSCL+/-P in this population. CONCLUSIONS: Our results suggest that the 8q24.21 locus is not associated with susceptibility to NSCL+/-P in Japanese patients and provide further evidence that ethnicity is a strong factor in determining susceptibility loci, albeit using a limited number of samples. Further studies are needed to identify regions involved in the development of NSCL+/-P in the Japanese population. PMID- 21981553 TI - Penile duplex ultrasonography in men with Peyronie's disease: is it veno occlusive dysfunction or poor cavernosal arterial inflow that contributes to erectile dysfunction? AB - INTRODUCTION: At least 20% of men with Peyronie's disease (PD) suffer from erectile dysfunction (ED). The fundamental mechanism is thought to arise from the progression of penile fibrosis, which was initially limited to the PD plaque within the tunica albuginea. However, recent studies have highlighted the possibility of fibrosis of the cavernosal vessel media wall leading to impairment of arterial inflow. AIM: To evaluate the penile duplex ultrasonographic findings in PD of impotent men and to determine whether early features of PD might predict clinical progression. MAIN OUTCOME MEASURES: Patient demographic, comorbidities, International Index of Erectile Function-5 scores, surgical intervention, and physical findings were documented. Penile curvature, plaque size, and peak systolic velocity (PSV) and end-diastolic velocity (EDV) on color duplex ultrasonography (CDU) were recorded. METHODS: We performed a retrospective review of all men presenting with penile curvature and length loss who underwent penile CDU between January 2001 and January 2010. RESULTS: A total of 1,120 men underwent penile CDU during the 10-year period. Complete information was obtained in 810 men; 250 men complained of decreased penile rigidity, while 150 men were unable to sustain erection. Comorbidities were similar between men with PD with and without ED. Tunical thickening (65%) was the most common CDU feature, and mean cumulative calcifications was 24.2 mm(2) (1-360 mm(2) , standard deviation 76). The PSV and EDV on the right cavernosal artery were 14.2 cm/second and 3.5 cm/second, while the left cavernosal artery measurements were 15.1 cm/second and 3.2 cm/second. Multivariate logistic regression model showed strong correlation between plaque size and development of ED. Both veno-occlusive dysfunction and impaired cavernosal arterial inflow were associated with ED. CONCLUSIONS: Veno occlusive dysfunction and impaired cavernosal arterial inflow contributed to the development of ED, and larger plaque size is a strong predictor of surgical intervention. PMID- 21981554 TI - Wrinkle engineering: a new approach to massive graphene nanoribbon arrays. AB - Wrinkles are often formed on CVD-graphene in an uncontrollable way. By designing the surface morphology of growth substrate together with a suitable transfer technique, we are able to engineer the dimension, density, and orientation of wrinkles on transferred CVD-graphene. Such kind of wrinkle engineering is employed to fabricate highly aligned graphene nanoribbon (GNR) arrays by self masked plasma-etching. Strictly consistent with the designed wrinkles, the density of GNR arrays varied from ~0.5 to 5 GNRs/MUm, and over 88% GNRs are less than 10 nm in width. Electrical transport measurements of these GNR-based FETs exhibit an on/off ratio of ~30, suggesting an opened bandgap. Our wrinkle engineering approach allows very easily for a massive production of GNR arrays with bandgap-required widths, which opens a practical pathway for large-scale integrated graphene devices. PMID- 21981555 TI - Chronic supplementation with shark liver oil for reducing tumor growth and cachexia in walker 256 tumor-bearing rats. AB - We investigated the effect of chronic supplementation with shark liver oil (SLO), an antitumor supplement source of n-3 fatty acids and 1-O-alkylglycerols, alone and combined with coconut fat (CF), a source of saturated fatty acids, on Walker 256 tumor growth and cachexia. Male rats were supplemented daily and orally with SLO and/or CF (1 g per kg body weight) for 7 wk. After 7 wk, 50% of animals were subcutaneously inoculated with 3 * 10(7) Walker 256 tumor cells. After 14 days, the rats were killed, the tumors were removed for lipid peroxidation measurement, and blood was collected for glycemia, triacylglycerolemia, and lacticidemia evaluation. Liver samples were obtained for glycogen measurement. Unlike CF, supplementation with SLO promoted gain in body weight, reduction of tumor weight, and maintained glycemia, triacylglycerolemia, lacticidemia, and liver glycogen content to values similar to non-tumor-bearing rats. Combined supplementation of SLO with CF also showed a reversion of cachexia with gain in body mass, reduction of lacticidemia, maintaining the liver glycogen store, and reduction in tumor weight. SLO, alone or combined with CF, promoted increase of tumor lipid peroxidation. In conclusion, SLO supplemented chronically, alone or associated with CF, was able to reduce tumor growth and cachexia. PMID- 21981556 TI - Computational investigation of DNA detection using graphene nanopores. AB - Nanopore-based single-molecule detection and analysis have been pursued intensively over the past decade. One of the most promising applications in this regard is DNA sequencing achieved through DNA translocation-induced blockades in ionic current. Recently, nanopores fabricated in graphene sheets were used to detect double-stranded DNA. Due to its subnanometer thickness, graphene nanopores show great potential to realize DNA sequencing at single-base resolution. Resolving at the atomic level electric field-driven DNA translocation through graphene nanopores is crucial to guide the design of graphene-based sequencing devices. Molecular dynamics simulations, in principle, can achieve such resolution and are employed here to investigate the effects of applied voltage, DNA conformation, and sequence as well as pore charge on the translocation characteristics of DNA. We demonstrate that such simulations yield current characteristics consistent with recent measurements and suggest that under suitable bias conditions A-T and G-C base pairs can be discriminated using graphene nanopores. PMID- 21981557 TI - Tautomeric ratio and prototropic equilibrium constants of tenoxicam, a 1H and 13C NMR theoretical and experimental study. AB - The determination of the micro-equilibrium prototropic constants is often a tough task when the tautomeric ratio favors one of the species or when the chemical exchange is not slow enough to allow the quantitative detection of the tautomeric species. There are just few experimental methods available to reveal the constants of the tautomeric micro-equilibriums; its applicability depends on the nature of the tautomeric system. A combination of experimental and quantum chemistry calculated (1)H and (13)C NMR chemical shifts is presented here to estimate the population of the species participating in the tautomeric equilibriums of the tenoxicam, an important anti-inflammatory drug. A multivariate fitting of a fraction-mol-weighted contribution model, for the NMR chemical shifts of the species in solution, was used to find the populations of the tautomers of tenoxicam. To consider and evaluate the effect of the solvent polarity on the tautomers' populations, experimental determinations were carried out in DMSO-d(6), in an equimolar DMSO-H(2)O mixture of deuterated solvents and in D(2)O. Additionally, by employing HYPNMR, it has been possible to refine the acid-base macroscopic constants of tenoxicam. PMID- 21981558 TI - Differentiating cause-of-death terminology for deaths coded as sudden infant death syndrome, accidental suffocation, and unknown cause: an investigation using US death certificates, 2003-2004. AB - We compared written text on infant death certificates for deaths coded as sudden infant death syndrome (R95), unknown cause (R99), and accidental suffocation (W75). Using US mortality files supplemented with the death certifiers' written text for all infant deaths with International Classification of Diseases (ICD)-10 assigned codes R95, R99, and W75, we formed cause-of-death subcategories from common themes identified from the written text. Among all infant deaths in 2003 2004, the underlying cause of death was listed as R99 for 2128 deaths, R95 for 4408 deaths, and W75 for 931 deaths. Among the postneonatal deaths, the differences in subcategories varied between assigned ICD-10 codes: for R99-coded deaths, 45.8% were categorized as "Unknown" and 48.6% as "Pending"; for R95-coded deaths, 67.7% were categorized as "sudden infant death syndrome (SIDS)"; and for W75-coded deaths, 76.4% were categorized as "Suffocation." Examination of the written text on the death certificates demonstrates variability in the assigned ICD-10 codes which could have an important effect on the estimates of SIDS cases in the United States. PMID- 21981559 TI - The cost implications of the use of telmisartan or ramipril in patients at high risk for vascular events: the ONTARGET study. AB - BACKGROUND: The recently published ONTARGET trial found that telmisartan was non inferior to ramipril in reducing CV death, MI, stroke, or heart failure in patients with vascular disease or high-risk diabetes. The cost implications of ramipril and telmisartan monotherapy use based on the ONTARGET study are reported here. METHODS AND RESULTS: Only healthcare system costs were considered. Healthcare resource utilization was collected for each patient during the trial. The authors obtained country-specific unit costs to the different healthcare care resources consumed (i.e., hospitalizations events, procedures, non-study, and study drugs) for all enrolled patients. Purchasing power parities were used to convert country-specific costs into US dollars (US$ 2008). The total undiscounted costs of the study for the telmisartan group was $12,762 per patient and is higher than the ramipril group at $12,007 per patient, an un-discounted difference of $755 (95% confidence interval [CI], $218-$1292); The discounted costs for the telmisartan group was $11,722 compared with $11,019 for the ramipril group; a difference of $703 (95% CI, $209-$1197). The difference in costs is exclusively related to the acquisition cost of telmisartan over generic ramipril. LIMITATIONS: This analysis only considered direct healthcare system costs. Costs accrued outside the hospital were not collected. Combination therapy was excluded since it would likely be more expensive than ramipril alone, with no additional benefit and a risk of some harm. CONCLUSIONS: Based on these results, it is suggested that for the ONTARGET patients, the use of telmisartan instead of ramipril increases costs by 6.3%. These findings suggest that the choice to put patients on telmisartan should be justified based on the patient?s susceptibility to specific adverse events to minimize the cost implications. PMID- 21981560 TI - Health-related quality-of-life in patients after elective surgery for abdominal aortic aneurysm. AB - PURPOSE: The purpose of this study was to describe the health-related quality-of life (QoL) in patients after elective surgery for abdominal aortic aneurysm (AAA) compared to a normal population and to study the association between QoL and number of years since surgery. METHODS: All Danish men who underwent elective surgery for AAA at the age of 65 or more in the period from 1989-2007 in Denmark were invited to participate in the survey. Of 722 patients, 375 were alive and 328 (87%) responded. The instruments EQ-5D (European Quality of life), EQ-VAS and SF-12 (Short Form Health Survey) were applied for measuring health-related QoL. Multiple regression analysis was used to study the association between QoL and number of years since AAA surgery. RESULTS: A significantly poorer QoL was found in patients having had AAA surgery compared to the normal population as measured with the SF-12 and the EQ-VAS, but not with EQ-5D. A negative association between QoL and years following surgery was found with EQ-VAS and SF-12 (PCS), but not with the other instruments. DISCUSSION: Factors such as selection bias because of mortality and non-response may have resulted in an over-estimate of the QoL in patients having had AAA surgery, thus the difference in QoL compared to the normal population was probably under-estimated. The cross-section design was inefficient for the study of the association between QoL and years since surgery, and EQ-5D may be an insensitive instrument for measuring QoL in AAA patients after surgery. LIMITATIONS: The main limitation of the study was the cross sectional design. Males with a higher risk of death were under-represented in the sample. CONCLUSION: A poorer quality-of-life was found in patients having had elective AAA surgery compared to the normal population. PMID- 21981561 TI - Transfemorally or transapically deployed Sapien Edwards bioprosthesis is always deformed. AB - OBJECTIVE: To study the impact of femoral compared to apical access on the Sapien-Edwards (SE) prosthesis deployment and geometry in patients treated with transcatheter aortic valve implantation (TAVI) for aortic stenosis. BACKGROUND: SE prosthesis deformation exists after its deployment through transfemoral (TF TAVI) approach. However, no study comparing the deformation between TF-TAVI and transapical (TA-TAVI) approaches has yet been published. METHODS: Forty consecutive patients received TAVI with the SE prosthesis (TF-TAVI n = 25; TA TAVI n = 15). A fluoroscopic analysis of the prosthesis was then performed. The stent frame geometry was assessed during deployment in the profile view, and after implantation in the profile and frontal views. RESULTS: Expansion kinetics revealed a triphasic stent deployment with both approaches; the aortic extremity being the first to open. After implantation, on the profile view, the stent shape was never rectangular (therefore never cylindrical) in both groups. It had a biconic shape in most of the patients (76% vs. 93.3% for TF-TAVI and TA-TAVI patients, respectively, P = 0.224) with a wider aortic extremity relative to the ventricular one. The frontal view analysis showed that circular deployment of the stent was never achieved. A greater leaflet to stent mismatch was noted in TA TAVI patients, however, the difference was not statistically significant (12% vs. 33.3%, P = 0.126). CONCLUSION: Fluoroscopically assessed, the geometry of SE prosthesis was never cylindrical after deployment, whatever the access for implantation was. Longitudinal deformation was greater after TF-TAVI whereas leaflet to stent mismatch tended to be more pronounced after TA-TAVI. PMID- 21981562 TI - Telomeres and telomerase in Candida albicans. AB - Telomeres are the nucleoprotein structures at the ends of linear chromosomes and maintain the genomic integrity through multiple cell divisions. Telomeres protect the chromosome ends from degradation, end-to-end fusion and abnormal recombination and they also promote the end replication. The budding yeast Saccharomyces cerevisiae is the most well-studied model system with regard to telomere and telomerase regulation. Recently, the opportunistic fungal pathogen Candida albicans has emerged as an attractive model system for investigating telomere biology. Candida underwent rapid evolutionary divergence with respect to telomere sequences. Concomitant with the evolutionary divergence of telomere sequences, telomere repeat binding factors and telomerase components have also evolved, leading to differences in their functions and domain structures. Thus, the comparative analysis of the telomeres and telomerase-related factors in the budding yeast has provided a better understanding on both conserved and variable aspects of telomere regulation. In this review, I will discuss telomeres and telomerase-related factors and their functions in telomere and telomerase regulation in C. albicans. PMID- 21981492 TI - Search for three-jet resonances in pp collisions at square root(s)=7 TeV. AB - A search for three-jet hadronic resonance production in pp collisions at a center of-mass energy of 7 TeV has been conducted by the CMS Collaboration at the LHC, using a data sample corresponding to an integrated luminosity of 35 pb(-1). Events with high jet multiplicity and a large scalar sum of jet transverse momenta are analyzed using a signature-based approach. The number of expected standard model background events is found to be in good agreement with the observed events. Limits on the cross section times branching ratio are set in a model of gluino pair production with an R-parity-violating decay to three quarks, and the data rule out such particles within the mass range of 200 to 280 GeV/c2. PMID- 21981570 TI - Development of a measure to assess effective listening and interactive communication skills in the delivery of children's rehabilitation services. AB - PURPOSE: Therapists' listening and communication skills are fundamental to the delivery of children's rehabilitation services but few measures comprehensively assess these skills. The 24-item Effective Listening and Interactive Communication Scale (ELICS) was developed to reflect a multifaceted conceptualization based on evidence in the literature. METHOD: Data from 41 pediatric rehabilitation therapists (occupational, physical, speech-language, recreation, and behavioural therapists; psychologists and social workers) were used to determine the factor structure, internal consistency, and construct validity of the subscales. RESULTS: The measure contains four subscales with very good to excellent reliability: Consensus-oriented, Exploratory, Receptive, and Action-oriented Listening. Content validity was ensured by the development process. CONCLUSIONS: The ELICS portrays listening as a purposeful, goal oriented, and relational activity. The measure allows clinicians to assess and reflect on their listening/communication skills, and can be used to evaluate professional development activities and interventions geared to improving these skills. PMID- 21981572 TI - Comment on "Effects of triclocarban, triclosan, and methyl triclosan on thyroid hormone action and stress in frog and mammalian culture systems". PMID- 21981571 TI - Risk factors for microbial contamination of peripheral blood stem cell products. AB - BACKGROUND: Despite the well-known contamination rates and presence of microbial agents in stem cell products, the risk factors affecting microbial contamination have not been well described. STUDY DESIGN AND METHODS: In a 12-year period, we retrospectively reviewed culture results of peripheral blood stem cell products with the intent of identifying risk factors for microbial contamination. RESULTS: Microbial contamination was detected in 28 (5.7%) products of the postprocessing period and in 18 (3.66%) products of the postthawing period. Large-volume leukapheresis (LVL; odds ratio [OR], 5.85; 95% confidence interval [CI], 1.52 22.49; p = 0.01) and high numbers of stem cell culture sampling (OR, 1.4; 95% CI, 1.03-1.91; p = 0.03) were found to be risk factors for postprocessing bacterial contamination. The presence of postprocessing bacterial contamination was a risk factor for postthawing (OR, 28.89; 95% CI, 6.67-125.15; p < 0.001) and posttransplant (OR, 3.25; 95% CI, 1.24-8.50; p = 0.01) microbial growth. In transplants that were performed using contaminated products, the same pathogen was detected in 20% of patients and different pathogens were found in 35% of patients. CONCLUSION: Cultures should be carefully monitored in LVL products and in samples with high numbers of cultures performed. Growth of different bacterial pathogens must be considered in transplants that are performed with contaminated products. PMID- 21981573 TI - Compositional and quantitative microtextural characterization of historic paintings by micro-X-ray diffraction and Raman microscopy. AB - This work shows the benefits of characterizing historic paintings via compositional and microtextural data from micro-X-ray diffraction (MU-XRD) combined with molecular information acquired with Raman microscopy (RM) along depth profiles in paint stratigraphies. The novel approach was applied to identify inorganic and organic components from paintings placed at the 14th century Islamic University-Madrasah Yusufiyya-in Granada (Spain), the only Islamic University still standing from the time of Al-Andalus (Islamic Spain). The use of MU-XRD to obtain quantitative microtextural information of crystalline phases provided by two-dimensional diffraction patterns to recognize pigments nature and manufacture, and decay processes in complex paint cross sections, has not been reported yet. A simple Nasrid (14th century) palette made of gypsum, vermilion, and azurite mixed with glue was identified in polychromed stuccos. Here also a Christian intervention was found via the use of smalt, barite, hematite, Brunswick green and gold; oil was the binding media employed. On mural paintings and wood ceilings, more complex palettes dated to the 19th century were found, made of gypsum, anhydrite, barite, dolomite, calcite, lead white, hematite, minium, synthetic ultramarine blue, and black carbon. The identified binders were glue, egg yolk, and oil. PMID- 21981574 TI - Recruitment facilitation can promote coexistence and buffer population growth in metacommunities. AB - Although positive species interactions are ubiquitous in nature, theory has generally focused on the role of negative interactions to explain patterns of species diversity. Here, we incorporate recruitment facilitation, a positive interaction prevalent in marine and terrestrial systems, into a metacommunity framework to assess how the interplay between colonisation, competition and facilitation mediates coexistence. We show that when subordinate species facilitate the recruitment of dominant species, multi-species metacommunities can persist stably even if the colonisation rate of the dominant species is greater than that of the subordinate species. In addition, recruitment facilitation can buffer population growth from changes in colonisation rates, and thus explain the paradoxical mismatch between patterns of abundance and recruitment in marine systems. Overall, our results demonstrate that recruitment facilitation can have profound effects on the assembly, dissolution and regulation of metacommunities by mediating the relative influence of local and regional processes on population abundance and species diversity. PMID- 21981575 TI - Efficacy and safety of rituximab in common variable immunodeficiency-associated immune cytopenias: a retrospective multicentre study on 33 patients. AB - Patients with common variable immunodeficiency (CVID) are at high risk of developing immune thrombocytopenia (ITP) and/or autoimmune haemolytic anaemia (AHA). Given their underlying immunodeficiency, immunosuppressive treatment of these manifestations may increase the risk of infection. To assess efficacy and safety of rituximab in patients with CVID-associated ITP/AHA, a multicentre retrospective study was performed. Thirty-three patients, 29 adults and four children, were included. Patients received an average of 2.6 treatments prior to rituximab including steroids, intravenous immunoglobulin and splenectomy (21%). The median ITP/AHA duration at time of first rituximab administration was 12 months [range 1-324] and the indication for using rituximab was ITP (22 cases), AHA (n = 5) or both (n = 7); 1 patient was treated sequentially for ITP and then AHA. The overall initial response rate to rituximab was 85% including 74% complete responses. After a mean follow-up of 39 +/- 30 months after rituximab first administration, 10 of the initial responders relapsed and re-treatment with rituximab was successful in 7/9. Severe infections occurred after rituximab in eight adults (24%), four of whom were not on immunoglobulin replacement therapy. In conclusion, rituximab appears to be highly effective and relatively safe for the management of CVID-associated severe immune cytopenias. PMID- 21981576 TI - Carbon nanofibers decorated with poly(furfuryl alcohol)-derived carbon nanoparticles and tetraethylorthosilicate-derived silica nanoparticles. AB - The present paper introduces a novel method to functionalize nanofiber surfaces with carbon or silica nanoparticles by dip coating. This novel approach holds promise of significant benefits because dip coating of electrospun and carbonized nanofiber mats in poly(furfuryl alcohol) (abbreviated as PFA) is used to increase surface roughness by means of PFA-derived carbon nanoparticles produced at the fiber surface. Also, dip coating in tetraethylorthosilicate (abbreviated as TEOS) is shown to be an effective method for decorating carbon nanofibers with TEOS derived silica nanoparticles at their surface. Furthermore, dip coating is an inexpensive technique which is easier to implement than the existing methods of nanofiber decoration with silica nanoparticles and results in a higher loading capacity. Carbon nanofiber mats with PFA- or TEOS-decorated surfaces hold promise of becoming the effective electrodes in fuel cells, Li-ion batteries and storage devices. PMID- 21981578 TI - Bifunctional triterpene/sesquarterpene cyclase: tetraprenyl-beta-curcumene cyclase is also squalene cyclase in Bacillus megaterium. AB - This study demonstrates that a tetraprenyl-beta-curcumene cyclase, which was originally identified as a sesquarterpene cyclase that converts a head-to-tail type of monocycle to a pentacycle, also cyclizes a tail-to-tail type of linear squalene into a bicyclic triterpenol, 8alpha-hydroxypolypoda-13,17,21-triene. The 8alpha-hydroxypolypoda-13,17,21-triene was found to be a natural triterpene from B. megaterium. It was also demonstrated that cyclizations of both tetraprenyl beta-curcumene and squalene occurred with a purified B. megaterium TC homologue in the same reaction mixture. These results suggest that the tetraprenyl-beta curcumene cyclase is bifunctional, cyclizing both tetraprenyl-beta-curcumene and squalene in vivo. This is the first report describing a bifunctional terpene cyclase, which biosynthesizes two classes of cyclic terpenes with different numbers of carbons as natural products in the organism. PMID- 21981577 TI - New aryl hydrocarbon receptor homology model targeted to improve docking reliability. AB - The aryl hydrocarbon receptor (AhR) is a ligand-dependent, basic helix-loop-helix Per-ARNT-Sim (PAS) containing transcription factor that can bind and be activated by structurally diverse chemicals, including the toxic environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). As no experimentally determined structures of the AhR ligand binding domain (LBD) are available and previous homology models were only derived from apo template structures, we developed a new model based on holo X-ray structures of the hypoxia-inducible factor 2alpha (HIF-2alpha) PAS B domain, targeted to improve the accuracy of the binding site for molecular docking applications. We experimentally confirmed the ability of two HIF-2alpha crystallographic ligands to bind to the mAhR with relatively high affinity and demonstrated that they are AhR agonists, thus justifying the use of the holo HIF-2alpha structures as templates. A specific modeling/docking approach was proposed to predict the binding modes of AhR ligands in the modeled LBD. It was validated by comparison of the calculated and the experimental binding affinities of active THS ligands and TCDD for the mAhR and by functional activity analysis using several mAhR mutants generated on the basis of the modeling results. Finally the ability of the proposed approach to reproduce the different affinities of TCDD for AhRs of different species was confirmed, and a first test of its reliability in virtual screening is carried out by analyzing the correlation between the calculated and experimental binding affinities of a set of 14 PCDDs. PMID- 21981579 TI - Classification of Salmonella enterica serotypes from Australian poultry using repetitive sequence-based PCR. AB - AIMS: To evaluate a semi-automated repetitive extragenic palindromic sequence based PCR (rep-PCR) system for the classification of Salmonella serotypes from Australian poultry. METHODS AND RESULTS: Using a DNA fingerprint library within the DiversiLab((r)) System, four separate databases were constructed (serogroup B, C, E and Other). These databases contained 483 serologically confirmed (reference laboratory) Salmonella isolates. A blinded set of Salmonella cultures (n = 155) were typed by rep-PCR, matched against the internal library and compared with traditional serotyping. The predicted (Kullback-Leibler) serotype of 143 (92.3%) isolates matched traditional typing (P < 0.05). Of the 12 (7.7%) remaining isolates, ten (6.5%) resulted in 'No Match', one (0.65%) was incorrectly matched to the library (Salm. subsp 1 ser 4,12:-:-), and the other (0.65%) was referenced as Salm. ser. Sofia, whereas rep-PCR and in-house serotyping concurred as Salmonella serovar Typhimurium. Financial analysis showed higher material cost (215%) and a lower labour component (47.5%) for rep-PCR compared with serotyping. CONCLUSION: The DiversiLab((r)) System, with serogroup databases, was successfully implemented as an adjunct for reference serotyping of Salmonella enterica. SIGNIFICANCE AND IMPACT OF THE STUDY: The DiversiLab((r)) System platform is a cost-effective and easy-to-use system, which can putatively determine Salmonella enterica serotypes within a few hours. PMID- 21981580 TI - Surgical patient satisfaction as an outcome of nurses' caring behaviors: a descriptive and correlational study in six European countries. PMID- 21981581 TI - Presurgical presentation of columellar features, nostril anatomy, and alveolar alignment in bilateral cleft lip and palate after infant orthopedics with and without nasoalveolar molding. AB - OBJECTIVES: (1) To evaluate quantitative differences in presurgical presentations of alveolar alignment and nostril anatomy of infants with BCLP treated with nasoalveolar molding (NAM) from those treated with maxillary infant orthopedics only (IO) and (2) to detect interrelationships between presurgical nasoalveolar anatomy, age at lip surgery, age of commencing, and durations of alveolar and nasal molding. METHODS: A retrospective analysis was conducted on nasal-alveolar measurements and presurgical treatment records of infants with BCLP who received lip repair by a single surgeon in a tertiary-care, referral teaching hospital consecutively from 2000 to 2009 after undergoing NAM (n = 29; 51 nostrils) or IO (n = 17; 32 nostrils). Paired t tests analyzed nostril and alveolar symmetry in each group. Intergroup comparisons were made by linear mixed-model regression analyses. Pearson's correlation tests were conducted to detect significant interrelationships within groups. RESULTS: Significant between-group differences were noted in alveolar irregularity (NAM: 3.58 +/- 1.02 mm; IO: 7.31 +/- 1.28 mm; p < .01), columellar length (NAM: 2.88 +/- 0.27 mm; IO: 1.48 +/- 0.34 mm; p < .001), columellar width (NAM: 6.10 +/- 0.21 mm; IO: 6.88 +/- 0.26 mm; p < .01), columellar length/width ratio (NAM: 0.48 +/- 0.05; IO: 0.20 +/- 0.07; p < .05), and columellar angle (NAM: 0.98 +/- 1.1 degrees ; IO: 3.69 +/- 1.37 degrees ; p < .05). Differences in age of commencing presurgical orthopedics, lip surgery, and treatment durations were not significant. Better-aligned alveolar segments in the NAM group did not statistically correlate with nostril dimensions. Alveolar irregularity and nostril height in the IO group strongly correlated. CONCLUSIONS: Infants who received NAM had longer columellae and better-aligned alveolar segments than those who received only IO. Other nostril dimensions were not significantly different. PMID- 21981582 TI - Layer-by-layer assembled polyaniline nanofiber/multiwall carbon nanotube thin film electrodes for high-power and high-energy storage applications. AB - Thin film electrodes of polyaniline (PANi) nanofibers and functionalized multiwall carbon nanotubes (MWNTs) are created by layer-by-layer (LbL) assembly for microbatteries or -electrochemical capacitors. Highly stable cationic PANi nanofibers, synthesized from the rapid aqueous phase polymerization of aniline, are assembled with carboxylic acid functionalized MWNT into LbL films. The pH dependent surface charge of PANi nanofibers and MWNTs allows the system to behave like weak polyelectrolytes with controllable LbL film thickness and morphology by varying the number of bilayers. The LbL-PANi/MWNT films consist of a nanoscale interpenetrating network structure with well developed nanopores that yield excellent electrochemical performance for energy storage applications. These LbL PANi/MWNT films in lithium cell can store high volumetric capacitance (~238 +/- 32 F/cm(3)) and high volumetric capacity (~210 mAh/cm(3)). In addition, rate dependent galvanostatic tests show LbL-PANi/MWNT films can deliver both high power and high energy density (~220 Wh/L(electrode) at ~100 kW/L(electrode)) and could be promising positive electrode materials for thin film microbatteries or electrochemical capacitors. PMID- 21981583 TI - Biochemical outcome after high-dose-rate intensity modulated brachytherapy with external beam radiotherapy: 12 years of experience. AB - Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Biochemical control from series in which radical prostatectomy is performed for patients with unfavorable prostate cancer and/or low dose external beam radiation therapy are given remains suboptimal. The treatment regimen of HDR brachytherapy and external beam radiotherapy is a safe and very effective treatment for patients with high risk localized prostate cancer with excellent biochemical control and low toxicity. OBJECTIVE: * To investigate the long-term oncological outcome, during the PSA era, of patients with prostate cancer who were treated using high-dose-rate (HDR) brachy therapy (BT) combined with external beam radiation therapy (EBRT). PATIENTS AND METHODS: * From June 1998 to April 2007, 313 patients with localized prostate cancer were treated with 46 Gy of EBRT to the pelvis with a HDR-BT boost. * The mean (median) follow-up was 71 (68) months. * Toxicity was reported according to the Common Toxicity Criteria for Adverse Event, V.4. RESULTS: * The 10-year actuarial biochemical control was 100% for patients with no high-risk criteria, 88% for patients with two intermediate-risk criteria, 91% with one high-risk criterion and 79% for patients with two to three high-risk criteria (P= 0.004). * The 10 year cancer-specific survival was 97% (standard deviation +/- 1%). * The multivariate Cox regression analyses identified, Gleason score and T stage as independent prognostic factors for biochemical failure. * Gleason score was the only factor to significantly affect distant metastases. * Grade >= 3 late toxicity was not detected. CONCLUSION: * The 10-year results confirm the feasibility and effectiveness of EBRT with conformal HDR-BT boost for patients with localised prostate cancer. PMID- 21981584 TI - Body mass index and death rate of colorectal cancer among a national cohort of U.S. adults. AB - Substantial evidence suggests that increasing adiposity is associated with an increased death rate of colorectal cancer, but no studies were conducted among national representative populations in the United States. The current study examined the death rate across BMI levels in 7,016 adults who participated in the National Health and Nutrition Examination Survey in 1971-1975. BMI categories were defined as normal (18.5-24.9 kg/m(2)), overweight (25-29.9), and obese (>=30). A total of 519 cancer deaths were identified during a 17-yr follow-up with 118,998 person-years. No significantly increased death rates of total cancers, lung, breast, and prostate cancer were observed among participants with an increased BMI. However, colorectal cancer death rates were 0.39, 0.68, and 0.96/1,000 person-years, respectively, for normal weight, overweight, and obese (P value for log-rank trend test < 0.001), and the corresponding adjusted hazard ratios [95% confidence intervals (CI)] were 1.00 (reference), 1.25 (95% CI = 0.72 2.19), and 2.04 (1.08-3.83), respectively. No gender difference of the association was identified. The authors conclude that a significantly increased death rate of colorectal cancer was associated with excess body weight. The current study is an addition to the expanding body of literature indicating an increased risk of colorectal cancer development among the obese. PMID- 21981585 TI - Impact desolvation of polymers embedded in nanodroplets. AB - Using molecular dynamics simulation, we study the desolvation process of a polymer-loaded droplet after collision with a wall. The energy and time dependence of the process is analyzed for various droplet-polymer combinations. By changing droplet size, polymer size, solvent, and polymer species, separately, we can assess the influence of these factors individually. We find that the polymer is isolated for impact energies E per solvent molecule, which exceed a threshold value E(isol), which is of the order of the cohesive energy E(coh) of the solvent. The influence of the solvent can be quantified by the solute-solvent interaction energy per molecule E(ss). If the same polymer is embedded in solvents with similar E(coh), we find that desolvation proceeds more easily in the solvent with the smaller solute-solvent interaction energy per molecule E(ss). Polymers with high interaction energy need higher impact energies for complete desolvation. This interface energy also characterizes the desolvation of different polymers in the same solvent. E(isol) increases slowly with the size of the droplet and decreases with the size of the polymer. These findings may help to improve the production of intact isolated macromolecules out of their solutions. PMID- 21981586 TI - Primary and secondary skeletal blast trauma. AB - This study examines primary (resulting from blast wave) and secondary (resulting from disintegrated, penetrating fragments) blast trauma to the skeleton. Eleven pigs were exposed to semi-controlled blast events of varying explosive type, charge size, and distance, including some cases with shrapnel. Skeletal trauma was found to be extensive, presenting as complex, comminuted fractures with numerous small, displaced bone splinters and fragments. Traumatic amputation of the limbs and cranium was also observed. Fractures were concentrated in areas nearer the blast, but there was generally no identifiable point of impact. Fractures were more random in appearance and widespread than those typically associated with gunshot or blunt force injury events. These patterns appear to be uniquely associated with blast trauma and may therefore assist forensic anthropologists and other forensic examiners in the interpretation of skeletal trauma by enabling them to differentiate between blast trauma and trauma resulting from some other cause. PMID- 21981587 TI - Trends in zygomycosis in children. AB - Zygomycosis, or mucormycosis, is associated with significant morbidity and mortality in both children and adults. Studies in adults have shown an increase in the incidence of zygomycosis, particularly among haemtopoietic stem cell transplant (HSCT) recipients and patients with haematologic malignancies. There is a paucity of data on the epidemiology of zygomycosis in children. We performed a retrospective analysis to describe trends in zygomycosis between 1 January 2003 and 31 December 2010. We used the Pediatric Health Information System (PHIS) database to identify paediatric patients who were diagnosed with zygomycosis during the study period. Administrative data on diagnoses, demographics, underlying conditions and clinical experiences were collected. Summary statistics were calculated and tests for trend were conducted. We identified 156 unique patients with zygomycosis. The prevalence of zygomycosis did not significantly increase over time (P=0.284). The most common underlying condition was malignancy (58%) and over half received intensive care. Voriconazole utilisation among all hospitalised children significantly increased during the period (P=0.010). Our study demonstrates that the incidence of zygomycosis is not significantly increasing. During the time period there was a significant increase in the use of voriconazole among children. PMID- 21981588 TI - Percutaneous drainage of postoperative pericardial effusion in cardiac surgery. AB - BACKGROUND AND AIM OF THE STUDY: Postoperative pericardial effusion is frequent and can be complicated by cardiac tamponade. Although the different drainage techniques are well described in the setting of medical effusion, there is not a standard postoperative effusion treatment. The aim of this work was to assess the feasibility and effectiveness of the percutaneous pericardial drainage. METHODS: This a retrospective study involving 197 patients from 1990 to 2008. Drainage was performed by subxiphoid puncture (91.9%) or left parasternal puncture (8.1%) between 3 and 690 days following a cardiac procedure via median sternotomy. Effusion thickness was at least 10 mm in the subcostal echocardiography view. RESULTS: No deaths directly related to the procedure were observed. Complete and enduring drainage was achieved in 158 patients (80.2%). The procedure failed for 22 patients (11.2%) because no fluid was drained in 14 cases (7.1%) and a right ventricular puncture in 8 cases (4.1%). Recurrence of the effusion, which occurred for 17 patients (8.6%), was more frequent if an effusion of more than 5 mm persisted after the first drainage (P = 0.024) and if the drainage was performed outside the operating room because of emergency (P = 0.046). Risk factors for mortality were recurrence of the effusion (P = 0.04) and drainage performed outside the operating room (P = 0.007). CONCLUSIONS: Percutaneous pericardial drainage is effective to treat postoperative pericardial effusion. When the effusion is thicker than 10 mm and accessible, it can be the initial strategy and surgical drainage can serve as an alternate strategy in case of failure and complications of this procedure. PMID- 21981589 TI - Identification and structure elucidation of a p-phenoxybenzaldehyde in bamboo shoots by HPLC-ESI/MS/MS and NMR. AB - In this study, a derivative of p-phenoxybenzaldehyde in bamboo shoots was investigated. Bamboo shoots were ground and extracted with water, and an aqueous suspension was purified by SPE using Oasis HLB cartridges. After the SPE procedure, the analytes were analyzed by HPLC with refractive index detection (HPLC-RI). In the HPLC-RI analysis for sucralose, a putative sucralose was detected. In the subsequent HPLC-PDA analysis, the suspicious peak showed a unique UV absorption spectrum with the maximum wavelength at 285 nm indicating the existence of an aromatic ring. The contents of the unknown compound in bamboo shoot products ranged from 0.01 to 0.15 mg/g. The identity of the unknown compound was further confirmed by HPLC-ESI/MS/MS. The molecular weight of the unknown compound was determined to be 244. The chemical structure of the unknown compound was elucidated on the basis of NMR spectroscopic analyses ((1)H, (13)C, DEPT, COSY, HMQC, and HMBC). Finally, the structure of the unknown compound was characterized as 4-(4-dihydroxymethylphenoxy)benzaldehyde. PMID- 21981597 TI - Forest productivity under elevated CO2 and O3: positive feedbacks to soil N cycling sustain decade-long net primary productivity enhancement by CO2. AB - The accumulation of anthropogenic CO2 in the Earth's atmosphere, and hence the rate of climate warming, is sensitive to stimulation of plant growth by higher concentrations of atmospheric CO2. Here, we synthesise data from a field experiment in which three developing northern forest communities have been exposed to factorial combinations of elevated CO2 and O3. Enhanced net primary productivity (NPP) (c. 26% increase) under elevated CO2 was sustained by greater root exploration of soil for growth-limiting N, as well as more rapid rates of litter decomposition and microbial N release during decay. Despite initial declines in forest productivity under elevated O3, compensatory growth of O3 tolerant individuals resulted in equivalent NPP under ambient and elevated O3. After a decade, NPP has remained enhanced under elevated CO2 and has recovered under elevated O3 by mechanisms that remain un-calibrated or not considered in coupled climate-biogeochemical models simulating interactions between the global C cycle and climate warming. PMID- 21981598 TI - How do we ... integrate transfusion medicine and tissue dispensing programs in an academic medical center: response to a changing regulatory environment. PMID- 21981599 TI - Acute copper sulphate poisoning: a forgotten cause of severe intravascular haemolysis. PMID- 21981601 TI - Staged abdominal closure after small bowel or multivisceral transplantation. AB - Following paediatric SBMT, size discrepancy between the recipient's abdomen and the graft may lead to ACS, graft dysfunction, and death. We report our experience with SAC in these patients. Between 04/1993 and 03/2009, 57 children underwent 62 SBMTs. When abdominal wall tension seemed excessive for safe PAC, SAC was performed, using a Silastic(r) sheet and a vacuum occlusive dressing. Transplantations with SAC (23 combined liver and small bowel [CLB]) were compared with those with PAC [14 ISB and 25 CLB]. Indications for transplantation, preoperative status (after stratification for ISB/CLB transplants), age at transplantation, donor-to-recipient weight ratio, reduction in bowel and/or liver, and incidence of wound complications were not different in both groups. Post-operative intubation, stay in intensive care unit, and hospital stay were prolonged after SAC. Two deaths were related to ACS after PAC, none after SAC. Since 2000, one-yr patient survival is 73% after ISB transplantation and 57% vs. 75% after CLB transplantation with PAC vs. SAC, respectively (NS). SAC safely reduces severe ACS after paediatric SBMT and can be combined with graft reduction for transplantation of small recipients. PMID- 21981600 TI - Site-specific labeling of DNA and RNA using an efficiently replicated and transcribed class of unnatural base pairs. AB - Site-specific labeling of enzymatically synthesized DNA or RNA has many potential uses in basic and applied research, ranging from facilitating biophysical studies to the in vitro evolution of functional nucleic acids and the construction of various nanomaterials and biosensors. As part of our efforts to expand the genetic alphabet, we have developed a class of unnatural base pairs, exemplified by d5SICS-dMMO2 and d5SICS-dNaM, which are efficiently replicated and transcribed, and which may be ideal for the site-specific labeling of DNA and RNA. Here, we report the synthesis and analysis of the ribo- and deoxyribo variants, (d)5SICS and (d)MMO2, modified with free or protected propargylamine linkers that allow for the site-specific modification of DNA or RNA during or after enzymatic synthesis. We also synthesized and evaluated the alpha phosphorothioate variant of d5SICSTP, which provides a route to backbone thiolation and an additional strategy for the postamplification site-specific labeling of DNA. The deoxynucleotides were characterized via steady-state kinetics and PCR, while the ribonucleosides were characterized by the transcription of both a short, model RNA as well as full length tRNA. The data reveal that while there are interesting nucleotide and polymerase-specific sensitivities to linker attachment, both (d)MMO2 and (d)5SICS may be used to produce DNA or RNA site-specifically modified with multiple, different functional groups with sufficient efficiency and fidelity for practical applications. PMID- 21981602 TI - String kernels and high-quality data set for improved prediction of kinked helices in alpha-helical membrane proteins. AB - The reasons for distortions from optimal alpha-helical geometry are widely unknown, but their influences on structural changes of proteins are significant. Hence, their prediction is a crucial problem in structural bioinformatics. For the particular case of kink prediction, we generated a data set of 132 membrane proteins containing 1014 manually labeled helices and examined the environment of kinks. Our sequence analysis confirms the great relevance of proline and reveals disproportionately high occurrences of glycine and serine at kink positions. The structural analysis shows significantly different solvent accessible surface area mean values for kinked and nonkinked helices. More important, we used this data set to validate string kernels for support vector machines as a new kink prediction method. Applying the new predictor, about 80% of all helices could be correctly predicted as kinked or nonkinked even when focusing on small helical fragments. The results exceed recently reported accuracies of alternative approaches and are a consequence of both the method and the data set. PMID- 21981604 TI - Development and psychometric exploration of the professional practice environment assessment scale. AB - PURPOSE: Development of the Professional Practice Environment Assessment Scale (PPEAS) was based on the assumptions that a positive professional practice environment is more than and different from the absence of negative, abusive, or disrespectful behaviors by physicians; a positive professional practice environment improves patient outcomes as well as nurse and physician satisfaction; and a positive professional practice environment is characterized by mutual respect, understanding of roles, collaborative decision making, effective communication, and beliefs in the importance of nurse-physician relationships on patient outcomes. The PPEAS is intended as both a research tool and a method of assessing and monitoring changes in an organization's professional practice environment as it relates specifically to the impact the nurse and physician relationship has on the professional practice environment. The purpose of this study was to examine the psychometric properties of the PPEAS and determine if it was a valid and reliable instrument for assessing the positive attributes of the professional practice environment. DESIGN: A large acute care facility in the Midwestern section of the United States provided the setting for this psychometric study. The sample (N= 1,332) consisted of 801 nurses and 531 physicians. METHODS: Psychometric examination, which included principal component analysis with varimax rotation and assessment of internal consistency, was conducted to validate the reliability and validity of the PPEAS. FINDINGS: Analysis identified a four-factor solution. The four factors were classified as positive physician characteristics (five items), positive nurse characteristics (three items), collaborative decision making (two items), and positive beliefs in the value of the nurse-physician relationship (three items). Cronbach's alpha for the entire scale was .86, with subscales ranging from .73 to .89. CONCLUSIONS: Findings from this analysis support our model and provide evidence of the usefulness of this scale for assessing the presence of a positive professional practice environment. Using the total score, organizations can examine the status of their professional practice environment and examine changes in the environment over time. Subscale analysis can identify specific areas where the organization performs well and those areas in need of improvement. CLINICAL RELEVANCE: The professional practice environment has been implicated as a variable that impacts patient outcomes. The absence of negative physician behaviors is an inadequate measure for assessing the positive attributes of the professional practice environment. Instruments for assessing the professional practice environment typically looked at the presence of negative physician behaviors or examined a single aspect of the nurse-physician relationship. This article provides a theoretical framework that can be used to guide both practice and research. The PPEAS was developed within a theoretical framework that can be adapted to a variety of settings, cultures, and countries. The PPEAS is a valid and reliable instrument that can be used to assess the professional practice environment in a variety of settings. PMID- 21981605 TI - Guiding light in monolayers of sparse and random plasmonic meta-atoms. AB - Encouraged by the capacity of surface plasmons to confine and propagate electromagnetic fields, waveguiding concepts have been developed, including combinations of continuous metal films or ordered arrays of metal nanoparticles. So far, waveguiding in the latter systems has been based on near-field or diffractive coupling. Herein, we show that monolayers of sparse and disordered gold nanoparticles support a novel transverse-electric guided mode that, contrary to previous work, relies on the strong enhancement of the polarizability upon excitation of the nanoparticle LSPR, creating an effective refractive index sufficiently high to support light guidance over a large range of frequencies. Excitation of this guided mode offers interesting nanophotonics features and applications such as a tunable total absorption spectral band, attractive for light harvesting applications, or the generation of a large amplification of the sensitivity to changes of refractive index accompanied with striking enhancement of the limit of detection in real biosensing experiments. PMID- 21981606 TI - Peyronie's disease in teenagers. AB - INTRODUCTION: Peyronie's disease (PD) is commonly seen in middle-aged men, and little is known about this condition in teenagers. AIM: To investigate the characteristics of PD in teenagers. METHODS: The findings were compared between patients with the disease who were teenagers with those over 40 years of age. Statistical analyses were conducted to define differentiating features between these two groups. MAIN OUTCOME MEASURES: The demographics, clinical features, and associated comorbidities of patients with PD were reviewed. RESULTS: Thirty-two teenaged males were evaluated for PD in a single institution over a 10-year period. The median age for our cohort was 18 (15-19) years. Forty-five percent of patients had already been seen by another urologist, and 28% had been told they did not have PD. The mean duration of PD before seeking medical care in our cohort was 3 +/- 1 months. Sixteen percent of patients reported antecedent penile trauma, half of which happened during coitus or masturbation, and 18% of patients had hemoglobin (Hb) A1c levels > 5%. Dupuytren's contracture was not seen in this population. Twenty-two percent of patients presented with penile pain. Subsequent ED was seen in 37% of patients. Multiple noncontiguous plaques were seen in 37% of patients. Twelve percent were previously treated with vitamin E, while another 12% had previous intralesional verapamil. High distress was reported by 94% of patients. Thirty-four percent sought medical attention for anxiety/mood disorder, and 28% had a negative encounter with a sexual partner related to PD. All of the 32 patients had penile curvature with a mean of 32 +/- 12 degrees. Seventy-two percent of the patients had dorsal curvature while 22% had an associated deformity. Using duplex Doppler ultrasound, 12% had a calcified plaque, while none of the patients had abnormal hemodynamics. When compared with PD in adults, teenagers had greater than seven times the prevalence of multiple noncontiguous plaques (37% vs. 5%). Also, the prevalence of HbA1c level > 5% was higher in the teenagers as well (18% vs. 5%). CONCLUSIONS: PD does occur in teenagers often causing high distress levels. Compared to older adults, teenagers often present earlier, and more commonly have elevated HbA1c level and increased number of plaques at presentation. PMID- 21981607 TI - Insights into the functionality of pelletization aid in pelletization by extrusion-spheronization. AB - This study investigated the particle sizes of pelletization aids from the different wet processing steps of extrusion-spheronization, and their influence on rheological and pellet properties. Three commercial microcrystalline cellulose (MCC) grades, three commercial cross-linked polyvinyl pyrrolidone (X-PVP) grades and two agglomerated X-PVP grades (prepared using roller compaction from two commercial fine particle size X-PVP grades) were used as pelletization aid. The pelletization aids were analyzed for their dry state particle size, individual particle size (sonicated powder dispersion in water) and in-process particle sizes (dispersions of processed materials from the different processing steps). No remarkable particle size changes were observed with the commercial X-PVP grades under the different conditions. The two fine X-PVP grades, but not the coarse grade, produced good quality pellets. MCC and agglomerated X-PVP grades exhibited spectacularly lower individual and in-process particle sizes, and produced good quality pellets although some of them had dry state particle sizes comparable to that of the commercial coarse X-PVP grade. In-process particle sizes of pelletization aids correlated strongly with the rheological and pellet properties of the pelletization aid:lactose (1:3) binary mixtures. These results demonstrated that small in-process particle size of pelletization aid is a critical requirement for successful pelletization by extrusion-spheronization. PMID- 21981608 TI - Dansyl-naphthalimide dyads as molecular probes: effect of spacer group on metal ion binding properties. AB - Interaction of a few dansyl-naphthalimide conjugates 1a-e linked through polymethylene spacer groups with various metal ions was investigated through absorption, fluorescence, NMR, isothermal calorimetric (ITC), and laser flash photolysis techniques. The characteristic feature of these dyads is that they exhibit competing singlet-singlet energy transfer (SSET) and photoinduced electron transfer (PET) processes, both of which decrease with the increase in spacer length. Depending on the spacer group, these dyads interact selectively with divalent Cu(2+) and Zn(2+) ions, as compared to other mono- and divalent metal ions. Jobs plot analysis showed that these dyads form 2:3 complexes with Cu(2+) ions, while 1:1 complexes were observed with Zn(2+) ions. The association constants for the Zn(2+) and Cu(2+) complexes were determined and are found to be in the order 10(3)-10(5) M(-1). Irrespective of the length of the spacer group, these dyads interestingly act as fluorescence ratiometric molecular probes for Cu(2+) ions by altering the emission intensity of both dansyl and naphthalimide chromophores. In contrast, only the fluorescence intensity of the naphthalimide chromophore of the lower homologues (n = 1-3) was altered by Zn(2+) ions. (1)H NMR and ITC measurements confirmed the involvement of both sulfonamide and dimethylamine groups in the complexation with Cu(2+) ions, while only the latter group was involved with Zn(2+) ions. Laser excitation of the dyads 1a-e showed formation of a transient absorption which can be attributed to the radical cation of the naphthalimide chromophore, whereas only the triplet excited state of the dyads 1a-e was observed in the presence of Cu(2+) ions. Uniquely, the complexation of 1a-e with Cu(2+) ions affects both PET and SSET processes, while only the PET process was partially inhibited by Zn(2+) ions in the lower homologues (n = 1-3) and the higher homologues exhibited negligible changes in their emission properties. Our results demonstrate that the spacer length dependent variations of the photophysical properties of these novel conjugates not only enable the selective detection of Cu(2+) and Zn(2+) ions but also aid in discriminating these two biologically important metal ions. PMID- 21981609 TI - Microbubble-mediated ultrasonic techniques for improved chemotherapeutic delivery in cancer. AB - BACKGROUND: Ultrasound (US) exposed microbubble (MB) contrast agents have the capability to transiently enhance cell membrane permeability. Using this technique in cancer treatment to increase the efficiency of chemotherapy through passive, localized delivery has been an emerging area of research. PURPOSE: Investigation of the influence of US parameters on MB-mediated drug delivery in cancer. METHODS: The 2LMP breast cancer cells were used for in vitro experiments and 2LMP tumor-bearing mice were used during in vivo experiments. Changes in membrane permeability were investigated after the influence of MB-mediated US therapy parameters (i.e. frequency, mechanical index, pulse repetition period, US duration, and MB dosing and characteristics) on cancer cells. Calcein, a non permeable fluorescent molecule, and Taxol, chemotherapeutic, were used to evaluate membrane permeability. Tumor response was also assessed histologically. RESULTS: Combination chemotherapy and MB-mediated US therapy with optimized parameters increased cancer cell death by 50% over chemotherapy alone. DISCUSSION: Increased cellular uptake of chemotherapeutic was dependent upon US system parameters. CONCLUSION: Optimized MB-mediated US therapy has the potential to improve cancer patient response to therapy via increased localized drug uptake, which may lead to a lowering of chemotherapeutic drug dosages and systemic toxicity. PMID- 21981610 TI - Effects of beta-carotene supplements on cancer prevention: meta-analysis of randomized controlled trials. AB - This meta-analysis aimed to investigate the effects of beta-carotene supplements alone on cancer prevention as reported by randomized controlled trials (RCTs). We searched PubMed, EMBASE, and CENTRAL. Among the 848 articles searched, 6 randomized controlled trials, including 40,544 total participants, 20,290 in beta carotene supplement groups, and 20,254 in placebo groups, were included in the final analysis. In a meta-analysis of 6 RCTs, beta-carotene supplements had no preventive effect on either cancer incidence [relative risk (RR) = 1.08, 95% confidence interval (CI) = 0.99-1.18] or cancer mortality (RR = 1.00, 95% CI = 0.87-1.15). Similar findings were observed in both primary prevention trials and secondary prevention trials. Subgroup analyses by various factors revealed no preventive effect of beta-carotene supplementation on cancer prevention and that it significantly increased the risk of urothelial cancer, especially bladder cancer (RR = 1.52, 95% CI = 1.03-2.24) and marginally increased the risk of cancer among current smokers (RR = 1.07, 95% CI = 0.99-1.17). The current meta analysis of RCTs indicated that there is no clinical evidence to support the overall primary or secondary preventive effect of beta-carotene supplements on cancer. The potential effects, either beneficial or harmful, of beta-carotene supplementation on cancer should not be overemphasized. PMID- 21981611 TI - Transport across Caco-2 cell monolayer and sensitivity to hydrolysis of two anxiolytic peptides from alphas1-casein, alpha-casozepine, and alphas1-casein-f91 97: effect of bile salts. AB - alpha-Casozepine and f91-97, peptides from alpha(s1)-casein, display anxiolytic activity in rats and may have to cross the intestinal epithelium to exert this central effect. We evaluated their resistance to hydrolysis by the peptidases of Caco-2 cells and their ability to cross the cell monolayer. To mimic physiological conditions, two preparations of bile salts were used in noncytotoxic concentrations: porcine bile extract and an equimolar mixture of taurocholate, cholate, and deoxycholate. The presence and composition of bile salts appeared to modulate the peptidase activities of the Caco-2 cells involved (i) in the hydrolysis of alpha-casozepine, leading to much higher formation of fragments f91-99, f91-98, and f91-97, and (ii) in the hydrolysis of f91-97, leading to lower degradation of this peptide. Transport of alpha-casozepine across Caco-2 monolayer increased significantly, in the presence of bile extract, and of fragment f91-97, in the presence of bile salts. PMID- 21981612 TI - Onset of cutaneous vasculitis and exacerbation of IgA nephropathy after Bartonella henselae infection. AB - Bartonella henselae is the aetiological agent of cat-scratch disease. Recently, there have been reports of other conditions associated with this bacterium, including leucocytoclastic vasculitis, thrombocytopenic purpura, maculopapular and urticarial eruptions, granuloma annulare, erythema nodosum, erythema marginatum and erythema annulare. We report the first case, to our knowledge, of the simultaneous occurrence of cutaneous vasculitis and nephrotic syndrome in a 65-year-old woman with IgA nephropathy after a B. henselae infection transmitted by a cat scratch. The aetiopathogenetic role of B. henselae was hypothesized on the basis of the serological demonstration of acute B. henselae infection, the immunofluorescence findings, and the prompt resolution after azithromycin treatment. Patients reporting cat scratches or bites should undergo accurate clinical examination, routine laboratory examinations, urinalysis and clinical surveillance. PMID- 21981613 TI - Sequential quantitative X-ray elemental imaging of frozen-hydrated and freeze dried biological bulk samples in the SEM. AB - Planed frozen-hydrated (FH) bulk biological samples of chicken retina were analysed by X-ray elemental imaging in a scanning electron microscope and reanalysed after freeze-drying in the microscope column. Sequential elemental imaging of the same bulk sample in this way provides improved information on element distributions. There was no evidence of element redistribution during the freeze-drying process. Quantitative elemental images were obtained and interpreted to deduce relative and absolute element concentrations in different regions of the retina. Water concentrations were determined from the difference in oxygen concentrations at 15 kV and 5 kV in FH and freeze-dried (FD) samples, respectively. Two accelerating voltages were used to maintain similar X-ray excitation volumes. Water concentrations were also estimated by relating measured oxygen concentration in FH samples to the concentration of oxygen in solutions of a generalized protein in water and by comparing concentrations of phosphorous or sulphur in the FH and FD states. PMID- 21981614 TI - Genome gender diversity in affected sib-pairs with familial vesico-ureteric reflux identified by single nucleotide polymorphism linkage analysis. AB - Study Type - Aetiology (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Genetic linkage to distinguish loci for VUR has been previously described in several autosomal chromosomes. Although there are numerous explanations for the dissimilar findings, e.g. multifactorial etiology of VUR and hereditary miscellany among studied populations, clinical diversity between males and females may indicate a central gender-specific genetic susceptibility. Early studies suggested the presence of modified VUR gene(s) on the X-chromosome, accounting for the higher incidence of this disorder among female members in the pedigrees studied. On the other hand male-to-male transmission and a higher ratio of females to males argued against X-linked inheritance. More recently, additional chromosomal regions (i.e. chromosomes 1-7, 10-13, and 18-22) have been identified for VUR by using single nucleotide polymorphism-genome-wide linkage analysis. This is the first study to show that there is autosomal difference in VUR expression in males and females. This genotype variability may be the basis for the clinical differences between genders in children with VUR. OBJECTIVE: To assess gender-specific genetic differences in the susceptibility loci for vesico-ureteric reflux (VUR) in families who have two or more affected children. PATIENTS AND METHODS: A genome wide linkage analysis of VUR with high-density single nucleotide polymorphisms was conducted in 98 families with two or more affected children. A total of 221 affected offspring (123 sibling pairs) were included in the analysis. Genomic DNA was extracted from blood or saliva from all the patients. Data was stratified and analysed according to clinical presentation and gender of the proband and affected siblings. RESULTS: Using the affected sib-pair method, statistically significant peaks were found on chromosomes 1 (logarithm of odds, base10 [LOD] 4.4) and 5 (LOD 3.7) in males and on chromosomes 3 (LOD 3.5), 13 (LOD 4.5), and 15 (LOD 3.4) in females. CONCLUSION: This genotype variability might be the basis for the clinical differences between genders in children with VUR. Our data might be the first step to understanding the genetic background behind the gender specific differences of VUR and more clearly defining the genetically different subgroups of VUR. PMID- 21981615 TI - Alemtuzumab: right drug, right dose? PMID- 21981616 TI - Genome wide copy number analysis of paediatric Burkitt lymphoma using formalin fixed tissues reveals a subset with gain of chromosome 13q and corresponding miRNA over expression. AB - The majority of paediatric Burkitt lymphoma (pBL) patients that relapse will die of disease, but markers for this high-risk subset are unknown. MYC translocations characterize pBL, but additional genetic changes may relate to prognosis and serve as potential biomarkers. We utilized a molecular inversion probe single nucleotide polymorphism assay to perform high resolution, genome-wide copy number analysis on archival formalin-fixed, paraffin-embedded pBL and germline tissues. We identified copy number abnormalities (CNAs) in 18/28 patients (64%) with a total of 62 CNAs that included 32 gains and 30 copy number losses. We identified seven recurrent CNAs including 1q gain (7/28, 25%), 13q gain (3/28, 11%), and 17p loss (4/28, 14%). The minimum common amplified region on 13q was at 13q31 and included the MIR17HG (MIR17-92) locus. Samples with this gain had higher levels of MIR17 RNA and showed a tendency for early relapse. Tumour-specific uniparental disomy was identified in 32% of cases and usually was recurrent. These results demonstrate that high-resolution copy number analysis can be performed on archival lymphoma tissue specimens, which has significance for the study of rare diseases. PMID- 21981617 TI - Bivalirudin used as alternative anticoagulant in carotid artery stenting: a single center observational study. AB - PURPOSE: To analyze and report the safety and effectiveness of bivalirudin in a large patient population undergoing carotid artery stenting (CAS). METHODS: Between January 2001 and November 2010 extracranial CAS was performed in 272 patients in our institution. These patients were stratified according to the anticoagulant used during the CAS procedure into 2 groups (bivalirudin n = 217 vs. unfractionated heparin [UFH] n = 55) and analyzed regarding bleeding complications and periprocedural (within 30 days) stroke and myocardial infarction (MI) rates. RESULTS: The combined end-point of death, stroke, and MI occurred in 12 patients (4.4%) with no significant difference between the groups (bivalirudin 4.6% vs. UFH 3.6% P value 0.96). Stroke rates were 1.8% in the bivalirudin and 1.8% in the UFH group (P value 1.00), with 4/5 strokes being nondisabling. Periprocedural MI was observed in 7 patients (2.1%) with no significant differences between the groups (bivalirudin 2.7% vs. UFH 1.8%, P value 0.94). Bleeding complications occurred in 13/272 patients (4.7%) with no significant difference between the groups (bivalirudin 3.6% vs. UFH 9.0%, P value 0.15). The first activated clotting time after administration of the anticoagulants was therapeutic in 209/217 (96%) in the bivalirudin group and in 30/55 (55%) in the UFH group (P < 0.001). CONCLUSIONS: In this single-center study, bivalirudin was a safe and efficient anticoagulation strategy for CAS and could be considered a therapeutic alternative to UFH. PMID- 21981618 TI - Design and characterization of tissue-specific extracellular matrix-derived microcarriers. AB - The three-dimensional (3D) extracellular matrix (ECM) environment plays a critical role in mediating normal cellular behavior and tissue organization. While commercially available microcarriers have shown promise, limited research has been conducted on the design of tissue-specific, custom-fabricated microcarriers, engineered to mimic the composition of the native ECM of cells or tissues of interest. Moving toward this goal, methods were developed to fabricate microcarriers from decellularized adipose tissue (DAT) via minimally-cytotoxic protocols. Characterization by microscopy confirmed the production of stable spherical microcarriers, with a microporous surface topography and porous interior. The mean diameter of the DAT microcarriers was 934+/-51 MUm, while the porosity was estimated as 29%+/-4% using liquid displacement. Stability and swelling behavior over 4 weeks indicated that the DAT microcarriers were effectively stabilized with the photochemical crosslinking agent rose bengal, with total protein release in a simulated physiological environment remaining below 10 MUg/mL at all time points. Preliminary cell culture studies with human adipose-derived stem cells (ASCs) in a spinner flask system indicated enhanced cell attachment and proliferation of ASCs on DAT microcarriers over 14 days, as compared with gelatin control microcarriers fabricated using similar methods. Testing confirmed injectability of the DAT microcarriers, further supporting the clinical potential of the approach for localized cell delivery and small volume augmentation in plastic and reconstructive surgery. Overall, tissue-specific microcarriers prepared from solubilized DAT were found to be highly supportive of human ASCs cultured in a 3D dynamic environment. PMID- 21981628 TI - Ethnicity and newborn outcomes: the case of African American women. AB - PURPOSE: Although previous studies have confirmed the relationship between socioeconomic status, ethnicity, education, and occupation on birth outcomes, less is known about the relationship of providers influence or hospital characteristics on birth outcomes for minority women. It is not well understood whether hospital or physician characteristics exert an equal or greater affect compared with maternal sociodemographic factors, particularly for Black childbearing women known to be at particular risk for adverse birth outcomes. DESIGN: This retrospective descriptive study sought to determine whether variation in neonatal birth outcomes for Black women was attributable to hospital characteristics, physician influence, or patient sociodemographics. METHODS: Fixed and random effects were conducted to empirically determine the relative importance of hospital, physician, and patient characteristics (partitioning the variation of differences in birth outcome to each component) using a large administrative dataset. FINDINGS: Considerable variability existed among hospitals over and above hospital ownership or number of hospital beds. CONCLUSIONS: Ethnicity was a statistically significant predictor of adverse outcomes, as was the number of prenatal visits and maternal education. There is a significant relationship between adverse newborn outcomes and ethnicity after controlling for hospital and physician characteristics. CLINICAL RELEVANCE: Ongoing birth disparities in African American childbearing women are a significant public policy issue with important research and clinical implications. This research adds to nursing knowledge by helping eliminate some factors previously thought to have contributed to the high incidence of perinatal complications for African American women and their newborns. PMID- 21981629 TI - A comparison of volume-reduced versus standard HLA/HPA-matched apheresis platelets in alloimmunized adult patients. AB - BACKGROUND: Our blood bank prepares, on indication or request, a volume-reduced (VR) platelet (PLT) product with greater than 95% reduced plasma content and a 15 fold higher PLT concentration, potentially minimizing adverse reactions due to plasma, in particular for human leukocyte antigen (HLA)/human PLT antigen (HPA) matched PLTs when minor ABO incompatibility cannot be avoided. Here we compared the clinical effectiveness of VR apheresis PLTs (APs) with standard APs. STUDY DESIGN AND METHODS: We performed a single-center cohort study among consecutive alloimmunized patients who received either HLA/HPA-matched standard APs and/or VR APs between 1994 and 2008. The endpoints were corrected count increments (CCIs), time to next transfusion, and frequency of adverse reactions. The CCI of VR PLTs was calculated using the PLT dose before volume reduction. Using a random effects model, 851 transfusions to 68 patients were evaluated for CCI and 731 transfusions to 64 patients for time to next transfusion. The frequency of reported adverse reactions was compared between the groups. RESULTS: The 1-hour CCI was 23% (95% confidence interval [CI], 9%-42%; p < 0.001) lower and the 24 hour CCI was 17% (95% CI, -11% to 59%; p = 0.278) lower after VR-APs. The mean time to next transfusion was similar: standard APs, 3.1 days (95% CI, 2.7-3.5); and VR-APs, 2.8 days (95% CI, 2.5-3.2). Eight adverse reactions were reported: 4 of 619 in the standard AP group and 4 of 1202 in the VR-AP group. CONCLUSION: VR APs showed lower 1- and 24-hour CCIs than standard-APs, which can be largely explained by the lower PLT dose of VR-APs. The benefits of plasma reduction should seriously be outweighed given these lower increments. PMID- 21981630 TI - Mn7 species with an S = 29/2 ground state: high-frequency EPR studies of a species at the classical/quantum spin interface. AB - A high spin (S) compound has been synthesized whose properties straddle the interface between the classical and quantum mechanical spin descriptions. The cluster [Mn(7)O(4)(pdpm)(6)(N(3))(4)](ClO(4))(2) (Mn(7)) has an unprecedented core structure comprising an octahedral [Mn(III)(6)(MU(4)-O)(MU(3)-O)(3)(MU(3) N(3))(4)](6+) unit with one of its faces capped by a Mn(II) ion. Magnetization and susceptibility studies indicate an S = (29/2) ground state, the maximum possible. Variable-temperature, high-frequency electron paramagnetic resonance (HF-EPR) spectra on powder and single-crystal samples of Mn(7) exhibit sharp spectral features characteristic of a quantum spin that are well resolved in a certain temperature range but which transform to a continuum of peaks characteristic of a classical spin in another; these features have been well reproduced by computer simulations. A fast Fourier transform analysis of the sharp spectral features and the low temperature EPR spectra suggests that more than one spin state are involved. PMID- 21981631 TI - Assessing the threat to montane biodiversity from discordant shifts in temperature and precipitation in a changing climate. AB - Mountains are centres of global biodiversity, endemism and threatened species. Elevational gradients present opportunities for species currently living near their upper thermal limits to track cooler temperatures upslope in warming climates, but only if changes in precipitation are sufficiently in step with temperature. We model local population extirpation risk for a range of temperature and precipitation scenarios over the next 100 years for 16 848 vertebrate species populations distributed along 156 elevational gradients. Average population extirpation risks due to warming alone were < 5%, but increased 10-fold, on average, when changes in precipitation were also considered. Under the driest scenarios (minimum predicted precipitation), local extirpation risks increased sharply (50-60%) and were especially worrisome for hydrophilic amphibians and montane Latin America (c. 80%). Realistic assessment of risks urgently requires improved monitoring of precipitation, better regional precipitation models and more research on the effects of changes in precipitation on montane distributions. PMID- 21981632 TI - Prevalence and characteristics of vibrator use among women who have sex with women. AB - INTRODUCTION: Research suggests that vibrator use may be more prevalent among lesbian/bisexual-identified women. However, previous research has been limited by small samples of lesbian- and bisexual-identified women and has not focused specifically on the characteristics of vibrator use between women. AIMS: The present study was designed in order to develop a comprehensive understanding of women's use of vibrators with their female sexual partners and to understand the extent to which vibrator use is related to their sexual experiences. METHODS: Data were collected via a cross-sectional web-based survey from 2,192 women living in the United States and the United Kingdom. All participants reported engaging in sexual behavior with only women in the previous year. MAIN OUTCOME MEASURES: Sociodemographic characteristics, vibrator use history, vibrator use perceptions, and the Female Sexual Function Index (FSFI). RESULTS: Over three quarters of women in the sample reported a history of vibrator use during solo masturbation/with a female partner and over a quarter of the sample reported use in the previous month. Participants who were older, white, and in a long-term relationship were the most likely to use a vibrator with a female partner in the previous year. Vibrator use lifetime history was unrelated to all FSFI subscales with the exception of pain for lesbian and queer-identified women. In contrast to lifetime use, participants who used a vibrator with a female sexual partner in the previous month scored higher on several of the FSFI domains than women who reported no vibrator use or vibrator use only during solo masturbation in the past month. CONCLUSIONS: Vibrator use was common among this sample of women who have sex with women. Women who reported recent vibrator use with other women had higher mean sexual functioning scores than women who reported no vibrator use or vibrator use only during masturbation. Implications for health-care providers are discussed. PMID- 21981634 TI - Isotope labeling studies on the formation of multiple addition products of alanine in the pyrolysis residue of glucose/alanine mixtures by high-resolution ESI-TOF-MS. AB - Pyrolysis was used as a microscale sample preparation tool to generate glucose/alanine reaction products to minimize the use of expensive labeled precursors in isotope labeling studies. The residue remaining after the pyrolysis at 250 degrees C was analyzed by electrospray time-of-flight mass spectrometry (ESI-TOF-MS). It was observed that a peak at m/z 199.1445 in the ESI-TOF-MS spectrum appeared only when the model system contained at least 2-fold excess alanine. The accurate mass determination indeed indicated the presence of two nitrogen atoms in the molecular formula (C(10)H(18)N(2)O(2)). To verify the origin of the carbon atoms in this unknown compound, model studies with [(13)U(6)]glucose, [(13)C-1]alanine, [(13)C-2]alanine, [(13)C-3]alanine, and [(15)N]alanine were also performed. Glucose furnished six carbon atoms, and alanine provides four carbon (2 * C-2 and 2 * C-3) and two nitrogen atoms. When commercially available fructosylalanine (N-attached to C-1) was reacted with only 1 mol of alanine, a peak at m/z 199.1445 was once again observed. In addition, when 3-deoxyglucosone (3-DG) was reacted with a 2-fold excess of alanine, a peak at m/z 199.1433 was also generated, confirming the points of attachment of the two amino acids at C-1 and C-2 atoms of 3-DG. These studies have indicated that amino acids can undergo multiple addition reactions with 1,2-dicarbonyl compounds such as 3-deoxyglucosone and eventually form a tetrahydropyrazine moiety. PMID- 21981635 TI - Wnt proteins in mineralized tissue development and homeostasis. AB - The past decade has seen rapid advancement in the dissection of the molecular events and players in the development and homeostasis of mineralized tissues, that is, teeth and bones. Much of this is due to research efforts toward the regeneration of these organs and also to develop treatments for pathologies of bone, especially osteoporosis. Of late, great interest has been focused on the Wnt family of proteins and their involvement in tooth and bone development and in the regulation of postnatal bone mass. The purpose of this review is to summarize these findings and to explore new areas of Wnt research such as Wnt?bone morphogenetic protein interactions and the exciting revelation of systemic serotonin being involved in bone mass regulation. PMID- 21981633 TI - Drug resistance and cellular adaptation to tumor acidic pH microenvironment. AB - Despite advances in developing novel therapeutic strategies, a major factor underlying cancer related death remains resistance to therapy. In addition to biochemical resistance, mediated by xenobiotic transporters or binding site mutations, resistance can be physiological, emerging as a consequence of the tumor's physical microenvironment. This review focuses on extracellular acidosis, an end result of high glycolytic flux and poor vascular perfusion. Low extracellular pH, pHe, forms a physiological drug barrier described by an "ion trapping" phenomenon. We describe how the acid-outside plasmalemmal pH gradient negatively impacts drug efficacy of weak base chemotherapies but is better suited for weakly acidic therapeutics. We will also explore the physiologic changes tumor cells undergo in response to extracellular acidosis which contribute to drug resistance including reduced apoptotic potential, genetic alterations, and elevated activity of a multidrug transporter, p-glycoprotein, pGP. Since low pHe is a hallmark of solid tumors, therapeutic strategies designed to overcome or exploit this condition can be developed. PMID- 21981636 TI - Synergistic effect of EMF-BEMER-type pulsed weak electromagnetic field and HPMA bound doxorubicin on mouse EL4 T-cell lymphoma. AB - We have investigated the effects of low-frequency pulsed electromagnetic field (LF-EMF) produced by BEMER device on experimental mouse T-cell lymphoma EL4 growing on conventional and/or athymic (nude) mice. Exposure to EMF-BEMER slowed down the growth of tumor mass and prolonged the survival of experimental animals. The effect was more pronounced in immuno-compromised nude mice compared to conventional ones. Acceleration of tumor growth was never observed. No measurable levels of Hsp 70 or increased levels of specific anti-EL4 antibodies were detected in the serum taken from experimental mice before and at different intervals during the experiment, i.e. before solid tumor appeared, at the time of its aggressive growth, and at the terminal stage of the disease. A significant synergizing antitumor effect was seen when EL4 tumor-bearing mice were simultaneously exposed to EMF-BEMER and treated with suboptimal dose of synthetic HPMA copolymer-based doxorubicin, DOX(HYD)-HPMA. Such a combination may be especially useful for heavily treated patients suffering from advanced tumor and requiring additional aggressive chemotherapy which, however, at that time could represent almost life-threatening way of medication. PMID- 21981637 TI - Dose emission and aerodynamic characterization of the terbutaline sulphate dose emitted from a Turbuhaler at low inhalation flow. AB - Previously, dose emission below 30 L min(-1) through DPI has not been routinely determined. However, during routine use some patients do not achieve 30 L min(-1) inhalation flows. Hence, the aim of the present study was to determine dose emission characteristics for low inhalation flows from terbutaline sulphate Turbuhaler. Total emitted dose (TED), fine particle dose (FPD) and mass median aerodynamic diameter (MMAD) of terbutaline sulphate Turbuhaler were determined using inhalation flows of 10-60 L min(-1) and inhaled volume of 4 L. TED and FPD increase significantly with the increase of inhalation flows (p <0.05). Flows had more pronounced effect on FPD than TED, thus, faster inhalation increases respirable amount more than it increases emitted dose. MMAD increases with decrease of inhalation flow until flow of 20L min(-1) then it decreases. In vitro flow dependent dose emission has been demonstrated previously for Turbuhaler for flow rates above 30 L min(-1) but is more pronounced below this flow. Minimal FPD below 30 L min(-1) suggests that during routine use at this flow rate most of emitted dose will impact in mouth. Flow dependent dose emission results suggest that Pharmacopoeias should consider the use variety of inhalation flows rather than one that is equivalent to pressure drop of 4 KPa. PMID- 21981639 TI - Use of tumescent anaesthesia in dermatological surgery. PMID- 21981638 TI - Beyond drug use: a systematic consideration of other outcomes in evaluations of treatments for substance use disorders. AB - Across the addictions field, the primary outcome in treatment research has been reduction in drug consumption. A comprehensive view of the impact of substance use disorders on human functioning suggests that effective treatments should address the many consequences and features of addiction beyond drug use, a recommendation forwarded by multiple expert panels and review papers. Despite recurring proposals, and a compelling general rationale for moving beyond drug use as the sole standard for evaluating addiction treatment, the field has yet to adopt any core set of 'other' measures that are routinely incorporated into treatment research. Among the many reasons for the limited impact of previous proposals has been the absence of a clear set of guidelines for selecting candidate outcomes. This paper is the result of the deliberations of a panel of substance abuse treatment and research experts convened by the National Institute on Drug Abuse to discuss appropriate outcome measures for clinical trials of substance abuse treatments. This paper provides an overview of previous recommendations and outlines specific guidelines for consideration of candidate outcomes. A list of outcomes meeting those guidelines is described and illustrated in detail with two outcomes: craving and quality of life. The paper concludes with specific recommendations for moving beyond the outcome listing offered in this paper to promote the programmatic incorporation of these outcomes into treatment research. PMID- 21981641 TI - Training and the public welfare. PMID- 21981642 TI - The quiet revolution: retractorless surgery for complex vascular and skull base lesions. AB - OBJECT: Smaller operative exposures, endoscopic approaches, and minimally invasive neurosurgery have emerged as a dominant trend in the modern era. In keeping with this evolution, the authors have recently eliminated the use of fixed retractors, instead employing dynamic retraction, with the use of handheld instruments. In the present study, the authors report the results of applying this strategy to challenging vascular and skull base lesions. METHODS: This 6 month study prospectively analyzed the use of retractorless surgery in a consecutive series of 223 patients with intracranial vascular or skull base lesions undergoing craniotomy. A single surgeon performed all operations. RESULTS: The microsurgical approaches (in descending order of frequency) included an orbitozygomatic craniotomy (77 patients [35%]), frontal (36 patients [16%]), retrosigmoid (27 patients [12%]), interhemispheric (16 patients [7%]), and lateral supracerebellar (15 patients [7%]). The most common lesions were aneurysms (83 lesions overall [37%]), 18 of which required a bypass. Of 159 vascular lesions, there were also 46 cavernous malformations (29%). Meningiomas were the most common skull base tumors (37 cases [58%]). Of the 223 patients, 7 cases of various vascular and skull base lesions required fixed retraction. Therefore, 97% of the cases were successfully treated without a self-retaining retractor system. CONCLUSIONS: Fixed retraction can be supplanted by dynamic retraction with surgical instruments, limiting the risk of retractor-induced tissue edema and injury. This quiet revolution has precipitated a major change in surgical techniques. Extensive dissection of arachnoidal planes, careful placement of the handheld suction device, patient positioning that enhances gravity retraction, the refinement of microsurgical instrumentation, and appropriate selection of the operative corridor all serve to obviate the need for fixed retraction in most intracranial procedures. Retractorless neurosurgery is an achievable goal, even when complex lesions of the vasculature and skull base are being treated. PMID- 21981643 TI - Adipose lesions of nerve: the need for a modified classification. AB - OBJECT: Adipose lesions of nerve are rare and poorly understood. Their current classification, although not universally accepted, generally includes lipomatosis of nerve with or without localized macrodactyly, and intra- as well as extraneural lipoma. The authors believe that the spectrum of these lesions and their interrelationships are not currently appreciated. They propose an adaptation to the existing framework to illustrate the expanding spectrum of adipose lesions of nerve by considering lipomatosis and lipoma singly or in combination. METHODS: Fourteen representative cases are presented to demonstrate not only the intraneural and extraneural examples of lipomatosis and lipoma, but also their anatomical combinations. RESULTS: Based on the cases presented and a careful literature review, a conceptual approach to the classification of adipose lesions of nerve is generated. This approach incorporates the 2 essential lesions, lipomatosis of nerve and lipoma, in both their intra- and extraneural forms. This permits expansion to encompass combinations. CONCLUSIONS: To press the concept that adipose tumors of nerve are a broad but interrelated spectrum of lesions, the authors propose modification of the present classification system. This approach provides an orderly platform for progress, reflects understanding of these interrelated lesions, and facilitates optimal treatment by distinguishing resectable from nonresectable components. PMID- 21981645 TI - Retractorless brain surgery. PMID- 21981644 TI - Therapeutic benefit of urocortin in rats with intracerebral hemorrhage. AB - OBJECT: Intracerebral hemorrhage (ICH) accounts for about 15% of all deaths due to stroke. It frequently causes brain edema, leading to an expansion of brain volume that exerts a negative impact on ICH outcomes. The ICH-induced brain edema involves inflammatory mechanisms. The authors' in vitro study shows that urocortin (UCN) exhibits antiinflammatory and neuroprotective effects. Therefore, the neuroprotective effect of UCN on ICH in rats was investigated. METHODS: Intracerebral hemorrhage was induced by an infusion of bacteria collagenase type VII-S or autologous blood into the unilateral striatum of anesthetized rats. At 1 hour after the induction of ICH, UCN (0.05, 0.5, and 5 MUg) was infused into the lateral ventricle on the ipsilateral side. The authors examined the injury area, brain water content, blood-brain barrier permeability, and neurological function. RESULTS: The UCN, administered in the ipsilateral lateral ventricle, was able to penetrate into the injured striatum. Posttreatment with UCN reduced the injury area, brain edema, and blood-brain barrier permeability and improved neurological deficits of rats with ICH. CONCLUSIONS: Posttreatment with UCN through improving neurological deficits of rats with ICH dose dependently provided a potential therapeutic agent for patients with ICH or other brain injuries. PMID- 21981646 TI - Alpha interferon augments the graft-versus-leukaemia effect of second stem cell transplants and donor lymphocyte infusions in high-risk paediatric leukaemias. PMID- 21981647 TI - Side effects of intradetrusor botulinum toxin injections on ejaculation and fertility in men with spinal cord injury: preliminary findings. AB - Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The beneficial effect of intradetrusor botulinum toxin (BT) injections on hyperactive bladders in individuals with spinal cord injury is known from the literature, but its potential effect on ejaculation and fertility through diffusion is not. As BT injection paralyses the bladder muscle, it may also paralyse the muscular envelopes of the adjacent reproductive organs and lead to potential negative side effects, which have not been studied yet. This study provides preliminary data on the potential negative side effects of BT injections on semen volume and retrograde ejaculation, as well as some potential beneficial effects on semen quality. OBJECTIVE: To investigate the effect of botulinum neurotoxin A on ejaculation potential and fertility. Intradetrusor injection of botulinum neurotoxin A is most commonly used nowadays to treat overactive bladder in patients with spinal cord injury (SCI). PATIENTS AND METHODS: Retrospective analyses were carried out of 11 patients with complete lesions from C5 to T6 who had received botulinum (BT) injections for their overactive bladder and who had undergone ejaculation tests before and after BT treatment. RESULTS: BT treatment was found effective in improving bladder function in up to 85% of the cases. While no patients maintained natural ejaculation following their SCI, BT treatment was found to increase the incidence of retrograde ejaculation (vibrostimulation) in 46% of cases and to diminish semen volume in 77% of cases, from an average of 1.8 mL to 1 mL. Semen quality was slightly improved following BT treatment, sperm mobility increased in 67% of cases, sperm vitality in 50% and semen culture improved in 43%. CONCLUSIONS: BT treatment has beneficial and detrimental effects on ejaculation function. The detrimental effects involve retrograde ejaculation and reduced semen volume, which are explained by the spread of toxin to the bladder neck, reducing its tonus, and to the smooth muscle sexual accessory organs, reducing the strength of their contraction. The beneficial effects are explained by the reduced contamination of the semen by urinary infection, which may improve spermatogenesis and subsequent semen quality. The results are discussed in terms of their clinical implications and advice to patients. PMID- 21981654 TI - Tertiary-treated municipal wastewater is a significant point source of antibiotic resistance genes into Duluth-Superior Harbor. AB - In this study, the impact of tertiary-treated municipal wastewater on the quantity of several antibiotic resistance determinants in Duluth-Superior Harbor was investigated by collecting surface water and sediment samples from 13 locations in Duluth-Superior Harbor, the St. Louis River, and Lake Superior. Quantitative PCR (qPCR) was used to target three different genes encoding resistance to tetracycline (tet(A), tet(X), and tet(W)), the gene encoding the integrase of class 1 integrons (intI1), and total bacterial abundance (16S rRNA genes) as well as total and human fecal contamination levels (16S rRNA genes specific to the genus Bacteroides ). The quantities of tet(A), tet(X), tet(W), intI1, total Bacteroides , and human-specific Bacteroides were typically 20 fold higher in the tertiary-treated wastewater than in nearby surface water samples. In contrast, the quantities of these genes in the St. Louis River and Lake Superior were typically below detection. Analysis of sequences of tet(W) gene fragments from four different samples collected throughout the study site supported the conclusion that tertiary-treated municipal wastewater is a point source of resistance genes into Duluth-Superior Harbor. This study demonstrates that the discharge of exceptionally treated municipal wastewater can have a statistically significant effect on the quantities of antibiotic resistance genes in otherwise pristine surface waters. PMID- 21981655 TI - Heparin promotes soluble VEGF receptor expression in human placental villi to impair endothelial VEGF signaling. AB - BACKGROUND: Severe preeclampsia is characterized by hypertension, renal injury and placental dysfunction. Prothrombotic disorders are discovered in 10-20% of women with preeclampsia, providing the rationale for prescribing low-molecular weight heparin (LMWH) in future pregnancies. Heparin has diverse molecular actions and appears to reduce the recurrence risk of preeclampsia in women without prothrombotic disorders. The placenta-derived anti-angiogenic splice variant protein soluble vascular endothelial growth factor (VEGF) receptor-1 (sFLT1) is strongly implicated in the pathogenesis of the underlying endothelial dysfunction. As the placental syncytiotrophoblast is the principal source of sFLT1, we tested the hypothesis that heparin suppresses placental sFLT1 secretion. METHODS AND RESULTS: First trimester placental villi exposed to LMWH (0.25-25 IU mL(-1)) in an in vitro explant model significantly increased the expression and release of sFLT1 by the syncytiotrophoblast into culture media, reducing phosphorylation of FLT1 and KDR receptors in cultured human umbilical vein endothelial cells. This response was significantly diminished in placental villi from healthy term pregnancies. Placental villi from severely preeclamptic pregnancies had a higher baseline sFLT1 release, compared with first trimester placental villi and did not respond to LMWH treatment. LMWH promoted villous cytotrophoblast proliferation (BrdU incorporation) and impaired syncytial fusion differentiation, causing syncytiotrophoblast apoptosis (by caspase 3&7 activity and TUNEL staining) and necrosis (ADP/ATP ratio). CONCLUSION: LMWH promotes sFLT1 synthesis and release from first trimester placental villi in a manner similar to that of severely preeclamptic placental villi, which antagonizes VEGF signaling in endothelial cells. These effects in part are mediated by an interaction between heparin and the cytotrophoblasts that regenerates the overlying syncytiotrophoblast responsible for sFLT1 secretion into the maternal blood. PMID- 21981656 TI - Clinical study on prevention of HBV re-infection by entecavir after liver transplantation. AB - PURPOSE: This aims to evaluate the effects of lamivudine (LAM) and entecavir (ETV) in preventing hepatitis B virus (HBV) re-infection after liver transplantation (LT). METHODS: A retrospective matched case-control method was used in this study. From June 2005 to May 2007, the patients who received LAM (100 mg qd) or ETV (0.5 mg qd) were chosen. The LAM and ETV groups were matched using a 3:1 ratio based on the factors, such as age, gender, LAM or ETV antiviral duration, primary disease, and HBV DNA levels at the initiation of antiviral therapy. Data on serum HBV markers, HBV DNA, and cumulative recurrence were collected. RESULTS: Two hundred and fifty-two patients were enrolled. The average duration of follow-up was 38.5 and 41.2 months (LAM and ETV groups) (p>0.05). Duration of pre-operative antiviral therapy was 30.3 and 25.8 d (LAM and ETV groups) (p>0.05). The HBV DNA level decreased from 3.89*10(6) to 5.31*10(5) copies/mL before LT in the LAM group, and decreased from 8.74*10(6) to 5.49*10(4) copies/mL in the ETV group (p<0.05). Eighteen patients in LAM group developed HBV re-infection and 0 in ETV group. CONCLUSION: ETV is superior to LAM for preventing HBV re-infection following LT. PMID- 21981657 TI - Assessment of cell viability in three-dimensional scaffolds using cellular auto fluorescence. AB - After assessing cell viability (CV), tissue-engineered constructs are often discarded, as current CV assays commonly require specific (fluorescent) dyes to stain cells and may need scaffold/tissue digestion before quantifying the live and dead cells. Here, we demonstrate and evaluate how cellular auto-fluorescence can be exploited to facilitate a noninvasive CV estimation in three-dimensional scaffolds using two advanced microscopy methods. Mixtures of live and dead C2C12 myoblasts (0%, 25%, 50%, 75%, and 100% live cells) were prepared, and CV was determined before seeding cells into collagen carriers using the trypan blue (TB) assay. Cell-seeded collagen gels ([CSCGs], n=5/cell mixture) were produced by mixing collagen solution with the live/dead cell mixtures (7*10(6) cells/mL). After polymerization, two-photon microscopy (TPM) and confocal microscopy images of the CSCG were acquired (n=30 images/CSCG). It was found that live and dead cells systematically emit auto-fluorescent light with different spectral characteristics. Viable cells showed predominantly blue fluorescence with a peak emission around 470 nm, whereas dead cells appeared to mainly emit green fluorescent light with a peak intensity around 560 nm. For TPM, live and dead cells were distinguished spectrally. For confocal images, the intensity ratio of images taken with band-pass filters was used to distinguish live from dead cells. CV values obtained with both TPM and confocal imaging did not significantly differ from those acquired with the established TB method. In comparison to TPM, confocal microscopy was found to be less accurate in assessing the exact CV in constructs containing mostly live or dead cells. In summary, monitoring cellular auto-fluorescence using advanced microscopy techniques allows CV assessment requiring no additional dyes and/or scaffold digestion and, thus, may be especially suitable for tissue-engineering studies where CV is measured at multiple time points. PMID- 21981658 TI - Trophozoite stage infected erythrocyte contents analysis by use of spectral imaging LED microscope. AB - This paper describes an application of both multispectral imaging system and multivariate analysis for the discrimination between healthy and prior malaria infected human erythrocytes contents. The multispectral microscope is based on LEDs illumination sources ranging from 375 nm to 940 nm and running with three geometries. Principal component and hierarchical clustering analysis have been applied effectively to differentiate the cells constituents. The trophozoite stage of plasmodium falciparum and its food vacuole, as well as 'haem' derivatives have been mapped. Our results reveal the potential of this technique, for malaria drug-target study, and earlier marker-free blood smear diagnosis. PMID- 21981659 TI - Functional platform for controlled subcellular distribution of carbon nanotubes. AB - As nanoparticles can cross different cellular barriers and access different tissues, control of their uptake and cellular fate presents a functional approach that will be broadly applicable to nanoscale technologies in cell biology. Here we show that the trafficking of single-walled carbon nanotubes (SWCNTs) through various subcellular membranes of the plant cell is facilitated or inhibited by attaching a suitable functional tag and controlling medium components. This enables a unique control over the uptake and the subcellular distribution of SWCNTs and provides a key strategy to promote their cellular elimination to minimize toxicity. Our results also demonstrate that SWCNTs are involved in a carrier-mediated transport (CMT) inside cells; this is a phenomenon that scientists could use to obtain novel molecular insights into CMT, with the potential translation to advances in subcellular nanobiology. PMID- 21981660 TI - Encoding phenotype in bacteria with an alternative genetic set. AB - An unnatural base-pair architecture with base pairs 2.4 A larger than the natural DNA-based genetic system (xDNA) is evaluated for its ability to function like DNA, encoding amino acids in the context of living cells. xDNA bases are structurally analogous to natural bases but homologated by the width of a benzene ring, increasing their sizes and resulting in a duplex that is wider than native B-DNA. Plasmids encoding green fluorescent protein were constructed to contain single and multiple xDNA bases (as many as eight) in both strands and were transformed into Escherichia coli. Although they yielded fewer colonies than the natural control plasmid, in all cases in which a modified plasmid (containing one, two, three, or four consecutive size-expanded base pairs) was used, the correct codon bases were substituted, yielding green colonies. All four xDNA bases (xA, xC, xG, and xT) were found to encode the correct partners in the replicated plasmid DNA, both alone and in longer segments of xDNA. Controls with mutant cell lines having repair functions deleted were found to express the gene correctly, ruling out repair of xDNA and confirming polymerase reading of the unnatural bases. Preliminary experiments with polymerase deletion mutants suggested combined roles of replicative and lesion-bypass polymerases in inserting correct bases opposite xDNA bases and in bypassing the xDNA segments. These experiments demonstrate a biologically functioning synthetic genetic set with larger-than-natural architecture. PMID- 21981661 TI - Machine perfusion following static cold storage preservation in kidney transplantation: donor-matched pair analysis of the prognostic impact of longer pump time. AB - The impact of machine perfusion (MP) time on kidney transplant outcome is mixed in previous studies using multivariable analyses. In an analysis of 66 pairs of donor-matched adult, first transplant recipients (N = 132) with identical donor characteristics except for pump time, tests of association of shorter versus longer pump time (first versus second kidney removed) by delayed graft function(DGF), slow graft function(SGF), and biopsy proven acute rejection(BPAR) were performed using McNemar's test. Freedom-from-BPAR, graft and patient survival, and renal function were also compared. Mean +/- SD pump times for paired recipients with first and second kidneys were 22.7 +/- 7.3 h and 31.2 +/- 7.9 h, respectively (mean difference: 8.5 +/- 4.5 h, P < .000001). There was no significant impact of pump time on DGF or SGF, with discordant pairs favoring less SGF with longer pump time (N.S.). The incidence of BPAR during the first 12 months post-transplant yielded a borderline difference favoring longer pump time (P = .09), and freedom-from-BPAR during the first 12 months was significantly more favorable for longer pump times (95% vs. 84%, P = 0.04). No differences were observed in graft and patient survival, and renal function. While offering significantly favorable protection from BPAR, this analysis of donor-matched recipient pairs corroborates longer MP (pump) times having no unfavorable effect on other clinical outcomes. PMID- 21981662 TI - Fatal transfusion-associated graft-versus-host disease with concomitant immune hemolysis in a group A combat trauma patient resuscitated with group O fresh whole blood. AB - Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare but well established fatal complication of blood transfusion. It can occur in immunocompetent patients when they receive transfusions from human leukocyte antigen-haploidentical donors who have lymphocytes with antigens that are not recognized as foreign by the host, but that recognize the host's tissues as foreign. It is generally viewed as a T-cell-mediated process. Graft-induced immune hemolysis or passenger lymphocyte syndrome is a well-described complication of marrow or solid organ transplantation in which immune competent donor B cells produce alloantibodies to recipient red blood cell (RBC) antigens and cause hemolysis of the recipient's RBCs. It is generally considered as a separate process from GVHD, although it could be considered a type of GVHD. Despite the theoretical possibility of both a B-cell and T-cell component to TA GVHD, detection of a humoral antibody in cases of acute TA-GVHD has not been described. We describe the clinical course and laboratory evaluation of a group A combat trauma patient who was acutely resuscitated with group O fresh whole blood and RBCs and group AB fresh-frozen plasma who experienced the onset of the clinical symptoms of TA-GVHD as well as the onset of hemolysis due to donor derived anti-A in his plasma 11 days after transfusion. PMID- 21981663 TI - Effect of cocrystallization techniques on compressional properties of caffeine/oxalic acid 2:1 cocrystal. AB - CONTEXT: Caffeine/oxalic acid 2:1 cocrystal exhibited superior stability to humidity over caffeine, but compressional behavior is not studied yet. OBJECTIVE: To compare compressional properties of caffeine/oxalic acid 2:1 cocrystal obtained by different cocrystallization techniques. MATERIALS AND METHODS: Cocrystal was obtained by solvent precipitation and ultrasound assisted solution cocrystallization (USSC) and characterized by X-ray powder diffraction and scanning electron microscopy. Compaction study was carried out at different compaction forces. Compact crushing strength, thickness and elastic recovery were determined. RESULTS AND DISCUSSION: Compaction was in order, caffeine > solvent precipitation cocrystal > USSC cocrystal. Caffeine exhibited sticking and lamination, where solvent precipitation compacts showed advantage. Caffeine and solvent precipitation compacts showed sudden drop in compactability, higher elastic recovery with severe lamination at 20,000 N. This was due to overcompaction. Crystal habit of two cocrystal products was same, but USSC cocrystals were difficult to compact. Uniform needle shaped USSC cocrystals must be difficult to orient in different direction and fracture during compression. Elastic recovery of USSC cocrystals was also more compared to other powders indicating less fracture and poor bonding between particles resulting in poor compaction. CONCLUSION: Cocrystal formation did not improve compressional property of caffeine. Cocrystals exposed to different crystallization environments in two techniques may have resulted in generation of different surface properties presenting different compressional properties. PMID- 21981664 TI - The use of chimeric vimentin citrullinated peptides for the diagnosis of rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and, in many cases, destruction of the joints. To prevent progressive and irreversible structural damage, early diagnosis of RA is of paramount importance. The present study addresses the search of new RA citrullinated antigens that could supplement or complement diagnostic/prognostic existing tests. With this aim, the epitope anticitrullinated vimentin antibody response was mapped using synthetic peptides. To improve the sensitivity/specificity balance, a vimentin peptide that was selected, and its cyclic analogue, were combined with fibrin- and filaggrin-related peptides to render chimeric peptides. Our findings highlight the putative application of these chimeric peptides for the design of RA diagnosis systems and imply that more than one serological test is required to classify RA patients based on the presence or absence of ACPAs. Each of the target molecules reported here (fibrin, vimentin, filaggrin) has a specific utility in the identification of a particular subset of RA patients. PMID- 21981665 TI - Androgen receptor gene polymorphisms and risk for androgenetic alopecia: a meta analysis. AB - BACKGROUND: Numerous studies have shown an association between polymorphisms in the androgen receptor gene (AR) and the risk for androgenetic alopecia (AGA), but the overall results are still controversial. AIM: To determine, by conducting a meta-analysis, whether the common AR gene polymorphisms confer susceptibility to AGA. METHODS: Publications addressing the association between AR gene polymorphisms and risk for AGA were selected from the PubMed, EMBASE and CBMdisc databases. Data were extracted from the studies by two independent reviewers. The meta-analysis was performed using the software programs RevMan (version 5.0.25) and STATA (version 9.2). From these data, odds ratio (OR) with 95% confidence interval (CI) was calculated. RESULTS: Only eight studies were found, reporting a total of 2074 patients with AGA and 1115 healthy controls. Three common polymorphisms of the AR gene were addressed: a StuI restriction-site polymorphism (rs6152, G>A), and CAG and GGC triplet-repeat polymorphisms. Meta-analysis results identified a significant association between the G allele of the AR StuI polymorphism and the risk for AGA (OR = 2.68, 95% CI 1.71-4.19, P < 0.01), especially in white populations (OR = 2.76, 95% CI 1.71-4.45, P < 0.01). No association was found between the CAG or GGC polymorphism and the risk for AGA (OR = 0.81, 95% CI 0.49-1.34, P = 0.41; OR = 1.01, 95% CI 0.47-2.14, P = 0.99, respectively). CONCLUSION: Our meta-analysis suggests that the G allele of AR StuI polymorphism might be a potential risk factor for AGA, especially in white populations. However, we did not find any obvious association of the CAG and GGC triplet-repeat polymorphisms of the AR gene with risk for AGA. PMID- 21981666 TI - Brain oscillations during spoken sentence processing. AB - Spoken sentence comprehension relies on rapid and effortless temporal integration of speech units displayed at different rates. Temporal integration refers to how chunks of information perceived at different time scales are linked together by the listener in mapping speech sounds onto meaning. The neural implementation of this integration remains unclear. This study explores the role of short and long windows of integration in accessing meaning from long samples of speech. In a cross-linguistic study, we explore the time course of oscillatory brain activity between 1 and 100 Hz, recorded using EEG, during the processing of native and foreign languages. We compare oscillatory responses in a group of Italian and Spanish native speakers while they attentively listen to Italian, Japanese, and Spanish utterances, played either forward or backward. The results show that both groups of participants display a significant increase in gamma band power (55-75 Hz) only when they listen to their native language played forward. The increase in gamma power starts around 1000 msec after the onset of the utterance and decreases by its end, resembling the time course of access to meaning during speech perception. In contrast, changes in low-frequency power show similar patterns for both native and foreign languages. We propose that gamma band power reflects a temporal binding phenomenon concerning the coordination of neural assemblies involved in accessing meaning of long samples of speech. PMID- 21981667 TI - Feedback-related brain potential activity complies with basic assumptions of associative learning theory. AB - Feedback-related negativity (FRN) is an ERP component that distinguishes positive from negative feedback. FRN has been hypothesized to be the product of an error signal that may be used to adjust future behavior. In addition, associative learning models assume that the trial-to-trial learning of cue-outcome mappings involves the minimization of an error term. This study evaluated whether FRN is a possible electrophysiological correlate of this error term in a predictive learning task where human subjects were asked to learn different cue-outcome relationships. Specifically, we evaluated the sensitivity of the FRN to the course of learning when different stimuli interact or compete to become a predictor of certain outcomes. Importantly, some of these cues were blocked by more informative or predictive cues (i.e., the blocking effect). Interestingly, the present results show that both learning and blocking affect the amplitude of the FRN component. Furthermore, independent analyses of positive and negative feedback event-related signals showed that the learning effect was restricted to the ERP component elicited by positive feedback. The blocking test showed differences in the FRN magnitude between a predictive and a blocked cue. Overall, the present results show that ERPs that are related to feedback processing correspond to the main predictions of associative learning models. PMID- 21981668 TI - Temporal dynamics of cognitive-emotional interplay in moral decision-making. AB - This study investigated the temporal dynamics of emotional and cognitive processing underlying decision-making in moral judgment. Thirty-seven participants were presented with a set of 60 dilemmas varying in whether killing one individual was an intended means to save others (instrumental dilemmas) or a foreseen but unintended consequence (incidental dilemmas). Participants were required to decide between Options A (letting a specific number of people die) and B (killing one person to save a specific number of people). ERPs were recorded to a slide displaying the letters A and B while subjects were deciding between the options, and movement-related potentials were recorded time-locked to the behavioral response, thus allowing the investigation of both stimulus- and response-related processes during decision-making. Ratings of emotional valence and arousal experienced during decision-making were collected after each decision. Compared with incidental dilemmas, instrumental dilemmas prompted a lower number of B choices and significantly more unpleasant decisions. A larger P260 component was found in the frontopolar and frontal areas when subjects were deciding on instrumental than incidental dilemmas, possibly reflecting an immediate affective reaction during the early stage of assessment and formation of preferences between available options. On the other hand, decisions on incidental dilemmas required greater attentional resources during the fairly controlled later processing, as reflected in the larger slow wave amplitudes. In addition, facilitation of action selection and implementation was found for incidental dilemmas during the second stage of decision-making, as supported by the larger amplitudes of both components of the Bereitschaftspotential. PMID- 21981669 TI - Specific neural traces for intonational discourse categories as revealed by human evoked potentials. AB - The neural representation of segmental and tonal phonological distinctions has been shown by means of the MMN ERP, yet this is not the case for intonational discourse contrasts. In Catalan, a rising-falling intonational sequence can be perceived as a statement or as a counterexpectational question, depending exclusively on the size of the pitch range interval of the rising movement. We tested here, using the MMN, whether such categorical distinctions elicited distinct neurophysiological patterns of activity, supporting their specific neural representation. From a behavioral identification experiment, we set the boundary between the two categories and defined four stimuli across the continuum. Although the physical distance between each pair of stimuli was kept constant, the central pair represented an across-category contrast, whereas the other pairs represented within-category contrasts. These four auditory stimuli were contrasted by pairs in three different oddball blocks. The mean amplitude of the MMN was larger for the across-category contrast, suggesting that intonational contrasts in the target language can be encoded automatically in the auditory cortex. These results are in line with recent findings in other fields of linguistics, showing that, when a boundary between categories is crossed, the MMN response is not just larger but rather includes a separate subcomponent. PMID- 21981670 TI - Rapid interactions between lexical semantic and word form analysis during word recognition in context: evidence from ERPs. AB - We used ERPs to investigate the time course of interactions between lexical semantic and sublexical visual word form processing during word recognition. Participants read sentence-embedded pseudowords that orthographically resembled a contextually supported real word (e.g., "She measured the flour so she could bake a ceke...") or did not (e.g., "She measured the flour so she could bake a tont...") along with nonword consonant strings (e.g., "She measured the flour so she could bake a srdt..."). Pseudowords that resembled a contextually supported real word ("ceke") elicited an enhanced positivity at 130 msec (P130), relative to real words (e.g., "She measured the flour so she could bake a cake..."). Pseudowords that did not resemble a plausible real word ("tont") enhanced the N170 component, as did nonword consonant strings ("srdt"). The effect pattern shows that the visual word recognition system is, perhaps, counterintuitively, more rapidly sensitive to minor than to flagrant deviations from contextually predicted inputs. The findings are consistent with rapid interactions between lexical and sublexical representations during word recognition, in which rapid lexical access of a contextually supported word (CAKE) provides top-down excitation of form features ("cake"), highlighting the anomaly of an unexpected word "ceke." PMID- 21981671 TI - On the automaticity of semantic processing during task switching. AB - There is growing evidence that processes formerly believed to be automatic are, in fact, strongly modulated by top-down influences. The purpose of the present work was to investigate how cognitive control can affect the purported automaticity of word processing by examining the impact of task switching on semantic processing using the ERP technique. In the context of the psychological refractory period dual-task paradigm, two experiments contrasted the context sensitive N400 ERP elicited by the second of two target words under conditions that involved either a task switch or no-task switch. Although the N400 was not affected by SOA in the absence of switching, it was strongly attenuated at short SOAs when the psychological refractory period procedure involved a switch from a perceptual to a semantic task (Experiment 1) or a switch between two different semantic tasks (Experiment 2). These findings suggest that semantic processing cannot be performed in parallel with task switching and illustrate limitations in the ability of the cognitive system to adapt flexibly to the dynamically changing challenges of the environment according to task demands and behavioral goals. PMID- 21981672 TI - Spatio-temporal brain dynamics mediating post-error behavioral adjustments. AB - Optimal behavior relies on flexible adaptation to environmental requirements, notably based on the detection of errors. The impact of error detection on subsequent behavior typically manifests as a slowing down of RTs following errors. Precisely how errors impact the processing of subsequent stimuli and in turn shape behavior remains unresolved. To address these questions, we used an auditory spatial go/no-go task where continual feedback informed participants of whether they were too slow. We contrasted auditory-evoked potentials to left lateralized go and right no-go stimuli as a function of performance on the preceding go stimuli, generating a 2 * 2 design with "preceding performance" (fast hit [FH], slow hit [SH]) and stimulus type (go, no-go) as within-subject factors. SH trials yielded SH trials on the following trials more often than did FHs, supporting our assumption that SHs engaged effects similar to errors. Electrophysiologically, auditory-evoked potentials modulated topographically as a function of preceding performance 80-110 msec poststimulus onset and then as a function of stimulus type at 110-140 msec, indicative of changes in the underlying brain networks. Source estimations revealed a stronger activity of prefrontal regions to stimuli after successful than error trials, followed by a stronger response of parietal areas to the no-go than go stimuli. We interpret these results in terms of a shift from a fast automatic to a slow controlled form of inhibitory control induced by the detection of errors, manifesting during low level integration of task-relevant features of subsequent stimuli, which in turn influences response speed. PMID- 21981673 TI - Noninvasively decoding the contents of visual working memory in the human prefrontal cortex within high-gamma oscillatory patterns. AB - The temporal maintenance and subsequent retrieval of information that no longer exists in the environment is called working memory. It is believed that this type of memory is controlled by the persistent activity of neuronal populations, including the prefrontal, temporal, and parietal cortex. For a long time, it has been controversially discussed whether, in working memory, the PFC stores past sensory events or, instead, its activation is an extramnemonic source of top-down control over posterior regions. Recent animal studies suggest that specific information about the contents of working memory can be decoded from population activity in prefrontal areas. However, it has not been shown whether the contents of working memory during the delay periods can be decoded from EEG recordings in the human brain. We show that by analyzing the nonlinear dynamics of EEG oscillatory patterns it is possible to noninvasively decode with high accuracy, during encoding and maintenance periods, the contents of visual working memory information within high-gamma oscillations in the human PFC. These results are thus in favor of an active storage function of the human PFC in working memory; this, without ruling out the role of PFC in top-down processes. The ability to noninvasively decode the contents of working memory is promising in applications such as brain computer interfaces, together with computation of value function during planning and decision making processes. PMID- 21981674 TI - Temporal profile of amygdala gamma oscillations in response to faces. AB - Neuroimaging studies have reported greater activation of the human amygdala in response to faces than to nonfacial stimuli, yet little is known about the temporal profile of this activation. We investigated this issue by recording the intracranial field potentials of the amygdala in participants undergoing preneurosurgical assessment (n = 6). Participants observed faces, mosaics, and houses in upright and inverted orientations using a dummy target detection task. Time-frequency statistical parametric mapping analyses revealed that the amygdala showed greater gamma-band activity in response to faces than to mosaics at 200 300 msec, with a peak at 255 msec. Gamma-band activation with a similar temporal profile was also found in response to faces versus houses. Activation patterns did not differ between upright and inverted presentations of stimuli. These results suggest that the human amygdala is involved in the early stages of face processing, including the modulation of subjective perception of faces. PMID- 21981675 TI - Electrophysiologically dissociating episodic preretrieval processing. AB - Contrasts between ERPs elicited by new items from tests with distinct episodic retrieval requirements index preretrieval processing. Preretrieval operations are thought to facilitate the recovery of task-relevant information because they have been shown to correlate with response accuracy in tasks in which prioritizing the retrieval of this information could be a useful strategy. This claim was tested here by contrasting new item ERPs from two retrieval tasks, each designed to explicitly require the recovery of a different kind of mnemonic information. New item ERPs differed from 400 msec poststimulus, but the distribution of these effects varied markedly, depending upon participants' response accuracy: A protracted posteriorly located effect was present for higher performing participants, whereas an anteriorly distributed effect occurred for lower performing participants. The magnitude of the posterior effect from 400 to 800 msec correlated with response accuracy, supporting the claim that preretrieval processes facilitate the recovery of task-relevant information. Additional contrasts between ERPs from these tasks and an old/new recognition task operating as a relative baseline revealed task-specific effects with nonoverlapping scalp topographies, in line with the assumption that these new item ERP effects reflect qualitatively distinct retrieval operations. Similarities in these effects were also used to reason about preretrieval processes related to the general requirement to recover contextual details. These insights, alongside the distinct pattern of effects for the two accuracy groups, reveal the multifarious nature of preretrieval processing while indicating that only some of these classes of operation are systematically related to response accuracy in recognition memory tasks. PMID- 21981676 TI - The influence of language proficiency on lexical semantic processing in native and late learners of English. AB - We investigated the influence of English proficiency on ERPs elicited by lexical semantic violations in English sentences, in both native English speakers and native Spanish speakers who learned English in adulthood. All participants were administered a standardized test of English proficiency, and data were analyzed using linear mixed effects (LME) modeling. Relative to native learners, late learners showed reduced amplitude and delayed onset of the N400 component associated with reading semantic violations. As well, after the N400 late learners showed reduced anterior negative scalp potentials and increased posterior potentials. In both native and late learners, N400 amplitudes to semantically appropriate words were larger for people with lower English proficiency. N400 amplitudes to semantic violations, however, were not influenced by proficiency. Although both N400 onset latency and the late ERP effects differed between L1 and L2 learners, neither correlated with proficiency. Different approaches to dealing with the high degree of correlation between proficiency and native/late learner group status are discussed in the context of LME modeling. The results thus indicate that proficiency can modulate ERP effects in both L1 and L2 learners, and for some measures (in this case, N400 amplitude), L1-L2 differences may be entirely accounted for by proficiency. On the other hand, not all effects of L2 learning can be attributed to proficiency. Rather, the differences in N400 onset and the post-N400 violation effects appear to reflect fundamental differences in L1-L2 processing. PMID- 21981677 TI - Theoretical study on the reaction mechanism of NH2(-) with O2 (a1Deltag). AB - A detailed theoretical study of the potential energy surface of poorly understood ion-molecule reaction of NH(2)(-) and O(2) (a(1)Delta(g)) is explored at the density functional theory B3LYP/6-311++G(d,p), ab initio of QCISD/6-311++G(d,p) and CCSD(T)/6-311++G(3df, 2pd) (single-point) theoretical levels for the first time. It is shown that there are six total possible products from P(1) to P(6) on the singlet potential energy surface. Among these, the charge-transfer product P(1) (NH(2) + O(2)(-)) is the most favorable product with predominant abundances, whereas P(4) (NO(-) + H(2)O) and P(2) (HNO + OH(-)) may be the second and third feasible products followed by the almost neglectable P(3) (NO(2)(-) + H(2)), while P(5) (c-NO(2)(-) + H(2)) and P(6) (ONO(-) + H(2)) will not be observed due to their either high barriers or being secondary products. The present theoretical study points out that besides P(1) (NH(2) + O(2)(-)) and P(2) (HNO + OH(-)), P(4) (NO(-) + H(2)O) should be also observed, which is different from the previous experiment study by Anthony Midey et al. in 2008. In addition, almost all of the reaction pathways to products are exothermic and the reaction rate should be very fast since the reaction barriers are very low except for P(5) (c NO(2)(-) + H(2)) which is in agreement with the measured total reaction rate constant k = 9.0 * 10(-10) cm(3)s(-1) at 300 K in the experiment study. It is expected that the present theoretical study may be helpful for the understanding of the reaction mechanism related to NHX(-), NX(2)(-), PHX(-), and PX(2)(-) (X = H, F, and Cl). PMID- 21981678 TI - Inhibition of the androgen receptor activity by Coprinus comatus substances. AB - Prostatic adenocarcinoma is the second leading cause of death from cancer in Western men. The common prostate cancer treatments are effective in the early stages; however, advanced prostate cancer is resilient to most of these treatments. Altered androgen receptor (AR) activity caused by point mutations or signaling mechanisms that regulate AR function has been proposed as a key mechanism in the transition to the androgen-independent stage. Our previous results demonstrated that hexane extract prepared from Coprinus comatus (C. comatus) strain 734 was able to interfere with AR activity. The current study was made to further evaluate the antiandrogenic activity of the C. comatus mushroom strain 734. Activity-guided chromatography was conducted and 2 active fractions, F-32-and F-33, were found to contain substances that were able to inhibit AR mediated reporter activity and reduce the levels of AR and prostate-specific antigen (PSA) transcripts in LNCaP cells. Fraction F-32 also inhibited the proliferation and clonigenicity of LNCaP cells. Furthermore, F-32 was able to inhibit the binding of AR to the PSA enhancer region and to inhibit Akt-mediated AR phosphorylation at Ser 213. This study illustrated the potential of substances from the C. comatus mushroom to serve as natural antiandrogenic modulators for the treatment of prostatic disorders. PMID- 21981679 TI - Oral microparticulate vaccine for melanoma using M-cell targeting. AB - Cancer vaccines are limited in their use, because of their inability to mount a robust anti-tumor immune response. Thus, targeting M-cells in the small intestine, which are responsible for entry of many pathogens, will be an attractive way to elicit a strong immune response toward particulate antigens. Therefore, in the present investigation, we demonstrated that efficient oral vaccination against melanoma antigens could be accomplished by incorporating the antigens in an albumin-based microparticle with a ligand AAL (Aleuria aurantia lectin) targeted specifically to M-cells. The oral microparticulate vaccine effectively protected the mice from subcutaneous challenge with tumor cells in prophylactic settings. The animals were vaccinated with antigen microparticles having a size range of around 1-1.25 um where one prime and four booster doses were administered every 14 days over 10 weeks of duration, followed by challenge with live tumor cells, which showed complete tumor protection after oral vaccination. With the inclusion of ligand in the microparticles, we observed significantly higher IgG titers (1565 MUg/mL) as compared to the microparticle formulations without AAL (872 MUg/mL). This data suggests that ligand loaded microparticles may have the potential to target antigens to M-cells for an efficient oral vaccination. PMID- 21981680 TI - Identification and thermal degradation kinetics of chlorophyll pigments and ascorbic acid from ditax nectar (Detarium senegalense J.F. Gmel). AB - Detarium senegalense J.F. Gmel (ditax) is a forest tree found in Senegal the fruits of which are characterized by an attractive green flesh with a high amount in ascorbic acid. It is generally consumed as a nectar in Senegal. In this study, the main pigments of ditax pulp were identified and quantified by HPLC-DAD. Pheophytin a (128 mg/kg), which represents 58% of the total pigments, followed by hydroxypheophytin a' (33 mg/kg), chlorophyll b (24 mg/kg), and chlorophyll a (20 mg/kg) was the major pigment of ditax pulp. Lutein and beta-carotene were present in lower amounts (4.6 and 3.6 mg/kg, respectively). The thermal degradation kinetics of pheophytin a, hydroxypheophytin a', and ascorbic acid were determined at temperatures ranging from 60 to 95 degrees C in ditax nectar. Pheophytin a was the most heat sensitive. Thermal processing induced the formation of degradation products such as pyropheophytin a and pyropheophytin b. The kinetics parameters have been calculated according to the models of Arrhenius, Eyring, and Ball. Following the Arrhenius relation, activation energies of pheophytin a, hydroxypheophytin a', and ascorbic acid were, respectively, 79, 74, and 46 kJ mol(-1). Losses calculated during isothermal treatments were close to experimental losses in pheophytin a, hydroxypheophytin a', and ascorbic acid. The Eyring model can then be used to predict chlorophyll pigments and vitamin C losses during pasteurization of the nectar (<10%). PMID- 21981681 TI - Is alcohol dependence best viewed as a chronic relapsing disorder? AB - This 'For Debate' paper starts by recognizing the growing trend towards considering alcohol dependence as a chronic relapsing disorder. We argue that the adoption of this model results from focusing on those in treatment for alcohol dependence rather than considering the larger number of people in the general population who meet criteria for alcohol dependence at some point in their lives. The majority of the general population who ever experience alcohol dependence do not behave as though they have a chronic relapsing disorder: they do not seek treatment, resolve their dependence themselves and do not relapse repeatedly. We suggest that caution is therefore needed in using the chronic relapsing disorder label. Our primary concerns are that this formulation privileges biological aspects of dependence to the detriment of psychological and social contributions, it inhibits much-needed developments in understanding alcohol dependence and leads to inefficient distributions of public health and clinical care resources for alcohol dependence. We invite debate on this issue. PMID- 21981682 TI - Tadalafil 2.5 or 5 mg administered once daily for 12 weeks in men with both erectile dysfunction and signs and symptoms of benign prostatic hyperplasia: results of a randomized, placebo-controlled, double-blind study. AB - INTRODUCTION: Erectile dysfunction (ED) and lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH-LUTS) commonly coexist in aging men. Tadalafil, a phosphodiesterase type 5 inhibitor approved for treating ED, is currently being evaluated for treating BPH-LUTS. AIMS: This multinational Phase 3 study assessed effects of tadalafil 2.5 or 5 mg once daily on ED and BPH-LUTS in men with both conditions during 12 weeks of double-blinded therapy. METHODS: Men were >= 45 years old, sexually active, and experiencing ED for >= 3 months and BPH-LUTS for >6 months. Randomization (baseline) followed a 4-week placebo lead in; changes from baseline were assessed via analysis of covariance and compared to placebo. A gatekeeping procedure controlled for multiple comparisons of co primary and key secondary measures at end point (last post-baseline observation). MAIN OUTCOME MEASURES: The co-primary measures were the International Index of Erectile Function-erectile function (IIEF-EF) domain and International Prostate Symptom Score (IPSS) score; key secondary measures were the Sexual Encounter Profile Question 3 (SEP Q3) and BPH Impact Index (BII). Treatment-emergent adverse events, serious adverse events, orthostatic vital signs, clinical laboratory and uroflowmetry parameters, and postvoid residual volume were assessed. RESULTS: Tadalafil 2.5 mg (N = 198) and 5 mg (N = 208) significantly improved IIEF-EF domain scores (both P < 0.001) vs. placebo (N = 200) at end point. For IPSS, improvements were significant with tadalafil 5 mg (P < 0.001), but not 2.5 mg, for observations from 2 weeks through end point (least-squares mean +/- standard error change from baseline at end point, placebo -3.8 +/- 0.5, tadalafil 2.5 mg -4.6 +/- 0.4, and 5 mg -6.1 +/- 0.4). Tadalafil 5 mg significantly improved SEP Q3 and BII (P < 0.001). Overall, tadalafil was well tolerated with no clinically adverse changes in orthostatic vital signs or uroflowmetry parameters. CONCLUSIONS: Tadalafil 5 mg significantly improved both ED and BPH-related outcomes through 12 weeks and was well tolerated. PMID- 21981683 TI - Targeted delivery of cargoes into a murine solid tumor by a cell-penetrating peptide and cleavable poly(ethylene glycol) comodified liposomal delivery system via systemic administration. AB - A liposomal delivery system with a high efficiency of accumulation in tumor tissue and then transportation of the cargo into tumor cells was developed here and evaluated via systemic administration. 1,2-Distearoyl-sn-glycero-3 phosphoethanolamine-poly(ethylene glycol)(2000) (DSPE-PEG(2000))-TAT and protective DSPE-PEG(2000) modified liposomes possessing good stability in 50% FBS (fetal bovine serum) and good uptake efficiency were used as the basic formulation (TAT-SL; SL = stealth liposome), and then longer cysteine (Cys) cleavable PEG(5000) was incorporated to modulate the function of TAT. All of the formulations to be used in vivo had sizes in a range of 80-100 nm and were stable in the presence of 50% FBS. Optical imaging showed that the incorporation of cleavable PEG(5000) into TAT-SL (i.e., C-TAT-SL) led to much more tumor accumulation and much less liver distribution compared with TAT-SL. The in vivo delivery profiles of C-TAT-SL were investigated using DiD as a fluorescent probe. Confocal laser scanning microscopy and flow cytometry showed that C-TAT-SL had a 48% higher (p < 0.001) delivery efficiency in the absence of Cys and a 130% higher (p < 0.001) delivery efficiency in the presence of Cys than the control (SL), indicating the successful targeted delivery of cargo was achieved by C-TAT SL via systemic administration especially with a subsequent administration of Cys. PMID- 21981684 TI - Partition constant and volume of distribution as predictors of clinical efficacy of lipid rescue for toxicological emergencies. AB - CONTEXT: Lipid infusion is useful in reversing cardiac toxicity of local anesthetics, and recent reports indicate it may be useful in resuscitation from toxicity induced by a variety of other drugs. While the mechanism behind the utility of lipid rescue remains to be fully elucidated, the predominant effect appears to be creation of a "lipid sink". OBJECTIVE: Determine whether the extraction of drugs by lipid, and hence the clinical efficacy of lipid rescue in toxicological emergencies can be predicted by specific drug properties. MATERIALS AND METHODS: Each drug investigated was added individually to human drug-free serum. Intralipid(r) was added to this drug-containing serum, shaken and then incubated at 37 degrees C. The lipid was removed by ultracentrifugation and the concentration of drug remaining in the serum was measured by high-pressure liquid chromatography. RESULTS: In this in vitro model, the ability of lipid emulsion to bind a drug was largely dependent upon the drug's lipid partition constant. Additionally, using a multiple linear regression model, the prediction of binding could be improved by combining the lipid partition constant with the volume of distribution together accounting for approximately 88% of the variation in the decrease in serum drug concentration with the administration of lipid emulsion. CONCLUSIONS: The lipid partition constant and volume of distribution can likely be used to predict the efficacy of lipid infusion in reversing the cardiac toxicity induced by anesthetics or other medications. PMID- 21981685 TI - ALSUntangled No. 12: Dean Kraft, Energy Healer. PMID- 21981696 TI - Implementation and external validation of Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score for predicting complications in 74 consecutive partial nephrectomies. AB - Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Partial nephrectomy (PN) is the gold standard operation for small renal tumours. The decision for or against a PN has been based mostly on preoperative radiological evaluation of the tumour. Three nephrometry scoring systems have been recently proposed for prediction of postoperative complications of PN (RENAL, C-index and PADUA). We validate externally the accuracy of the PADUA system and suggest for the first time a novel scoring system, based on the original PADUA system, which implements three other significant factors for the postoperative course of a partial. OBJECTIVE: * To externally validate the Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) classification of renal tumours managed by partial nephrectomy (PN). PATIENTS AND METHODS: * Seventy-four consecutive patients in a single academic tertiary institution underwent open PN. * Incidence of 90-day complications was stratified by several clinicopathological variables, such as gender, age of the patient, hospital stay, pathology report, tumour characteristics and positive surgical margins. PADUA scores were given to each case. * The severity of complications was also categorized with the Clavien system. RESULTS: * The optimal threshold of PADUA for the prediction of complications was 8 with a sensitivity equal to 90.9% and a specificity equal to 77.8% (area under the curve [AUC], 0.89; 95% confidence interval [CI], 0.73 1.00). * Multivariate analysis revealed that that PADUA is an independent predictor for the risk of complications. * Also, PADUA score >= 8 identified a group of patients with almost 20-fold higher risk of complications (hazard ratio [HR]= 19.82; 95% CI, 1.79-28.35; P= 0.015). * Patients with papillary histology had greater risk for complications than those with clear-cell tumours (HR = 4.88; 95% CI, 1.34-17.76; P= 0.016). CONCLUSIONS: * The PADUA score is a simple anatomical system that predicts the risk of postoperative complications. This is the first external validation of this system for open PN from a single centre. * The authors believe that PADUA is an efficient tool, since the only variable of the present study that predicted a higher incidence of complications was the histology type, which is determined after surgery. * However, it should be applied to laparoscopic and robot-assisted series and it could also include the ischaemia time and surgeon experience in the overall scoring to be complete. PMID- 21981697 TI - Platelet doubling after the first azacitidine cycle is a promising predictor for response in myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) patients in the Dutch azacitidine compassionate named patient programme. AB - The efficacy of azacitidine in the treatment of high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) (20-30% blasts) has been demonstrated. To investigate the efficacy of azacitidine in daily clinical practice and to identify predictors for response, we analysed a cohort of 90 MDS, CMML and AML patients who have been treated in a Dutch compassionate named patient programme. Patients received azacitidine for a median of five cycles (range 1-19). The overall response rate (complete/partial/haematological improvement) was 57% in low risk MDS, 53% in high risk MDS, 50% in CMML, and 39% in AML patients. Median overall survival (OS) was 13.0 (9.8-16.2) months. Multivariate analysis confirmed circulating blasts [Hazard Ratio (HR) 0.48, 95% confidence interval (CI) 0.24-0.99; P = 0.05] and poor risk cytogenetics (HR 0.45, 95% CI 0.22-0.91; P = 0.03) as independent predictors for OS. Interestingly, this analysis also identified platelet doubling after the first cycle of azacitidine as a simple and independent positive predictor for OS (HR 5.4, 95% CI 0.73-39.9; P = 0.10). In conclusion, routine administration of azacitidine to patients with variable risk groups of MDS, CMML and AML is feasible, and subgroups with distinct efficacy of azacitidine treatment can be identified. PMID- 21981698 TI - Impact of high-dose inotropic donor support on early myocardial necrosis and outcomes in cardiac transplantation. AB - BACKGROUND: Cardiac donors routinely require vasoactive agents for circulatory stability after brain death. Nevertheless, inotropes have been associated with direct cardiac toxicity. Our study evaluated whether the use of high-dose inotropic support in potential donors was associated with increased early myocardial necrosis (MN) and worse clinical outcomes after cardiac transplantation. METHODS: The UTAH Cardiac Transplant Program (UCTP) and Intermountain Donor Services databases were queried for records between 1996 and 2009. The high-dose donor inotropic support (HDIS) group was defined as patients on dopamine >10 MUg/kg/min. The incidence of early MN, intensive care unit (ICU) length of stay, length of ventilator support, and mortality was evaluated. RESULTS: Two hundred and forty-four recipients undergoing transplant met study criteria. The average donor age was 27 yr. The incidence of MN in the HDIS (n=29) and non-HDIS (n=204) groups was 14.8% and 6.7%, respectively, OR 2.67. Total ischemic time, ventilator support time, ICU stay, and actuarial survival were similar between both groups. CONCLUSION: The use of high-dose inotropic support to maintain donor stability appears to have a higher trend for early post transplant MN without an impact on clinical outcomes. With the current growing shortage of organ donors, it appears reasonable to use donors on high-dose inotropic support. PMID- 21981699 TI - A diruthenium catalyst for selective, intramolecular allylic C-H amination: reaction development and mechanistic insight gained through experiment and theory. AB - The mixed-valent paddlewheel complex tetrakis(2-oxypyridinato)diruthenium(II,III) chloride, [Ru(2)(hp)(4)Cl], catalyzes intramolecular allylic C-H amination with bis(homoallylic) sulfamate esters. These results stand in marked contrast to reactions performed with dirhodium catalysts, which favor aziridine products. The following discussion constitutes the first report of C-H amination using complexes such as [Ru(2)(hp)(4)Cl] and related diruthenium adducts. Computational and experimental studies implicate a mechanism for [Ru(2)(hp)(4)Cl]-promoted C-H amination involving hydrogen-atom abstraction/radical recombination and the intermediacy of a discrete, albeit short-lived, diradical species. The collective data offer a coherent model for understanding the preference of this catalyst to oxidize allylic (and benzylic) C-H bonds. PMID- 21981700 TI - Biological applications of rare-earth based nanoparticles. AB - Biomedicine and cell and molecular biology require powerful imaging techniques of the single molecule scale to the whole organism, either for fundamental science or diagnosis. These applications are however often limited by the optical properties of the available probes. Moreover, in cell biology, the measurement of the cell response with spatial and temporal resolution is a central instrumental problem. This has been one of the main motivations for the development of new probes and imaging techniques either for biomolecule labeling or detection of an intracellular signaling species. The weak photostability of genetically encoded probes or organic dyes has motivated the interest for different types of nanoparticles for imaging such as quantum dots, nanodiamonds, dye-doped silica particles, or metallic nanoparticles. One of the most active fields of research in the past decade has thus been the development of rare-earth based nanoparticles, whose optical properties and low cytotoxicity are promising for biological applications. Attractive properties of rare-earth based nanoparticles include high photostability, absence of blinking, extremely narrow emission lines, large Stokes shifts, long lifetimes that can be exploited for retarded detection schemes, and facile functionalization strategies. The use of specific ions in their compositions can be moreover exploited for oxidant detection or for implementing potent contrast agents for magnetic resonance imaging. In this review, we present these different applications of rare-earth nanoparticles for biomolecule detection and imaging in vitro, in living cells or in small animals. We highlight how chemical composition tuning and surface functionalization lead to specific properties, which can be used for different imaging modalities. We discuss their performances for imaging in comparison with other probes and to what extent they could constitute a central tool in the future of molecular and cell biology. PMID- 21981701 TI - Procoagulant effect of vitamin K antagonists? PMID- 21981702 TI - Anammox bacterial abundance, biodiversity and activity in a constructed wetland. AB - An integrated approach to document high anammox activity and biodiversity in a constructed wetland (CW) was performed and showed that substantial anammox activity could mitigate undesirable N(2)O emission. The enhanced anammox bacterial abundance, biodiversity and activity were achieved by supplementing activated sludge to the CW. Up to 3.38 * 10(7) gene copies g(-1) dry soil of anammox bacteria were enriched in the CW. The activity measured by isotope pairing technique increased from 1.6 nmol N g(-1) sludge h(-1) in the original activated sludge to 18 nmol N g(-1) soil h(-1) in the CW, with the specific cellular activity increased from 5.1 to 12.8 fmol cell(-1) d(-1). Up to 33% of produced N(2) could be attributed to anammox process in the CW, with the remainder being due to denitrification. Phylogenetic analysis of anammox bacterial 16S rRNA genes indicated a shift of community from single Candidatus "Brocadia fulgida" in sludge to multiple "Jettenia", "Brocadia", and "Anammoxoglobus" species in the CW. With static chambers and control experiments, the CW with supplemented sludge had a 30% reduced N(2)O emission flux compared with the tests without adding biomass during an 8 month testing period. PMID- 21981703 TI - Editorial: Cross my heart and hope to die: the use of pledges in health care. PMID- 21981705 TI - Commentary on Mao Q, Zhu L-X & Su X-Y (2011) A comparison of postnatal depression and related factors between Chinese new mothers and fathers. Journal of Clinical Nursing 20, 645-652. PMID- 21981704 TI - Using a Montessori method to increase eating ability for institutionalised residents with dementia: a crossover design. AB - AIMS: To investigate the efficacy of applying a Montessori intervention to improve the eating ability and nutritional status of residents with dementia in long-term care facilities. BACKGROUND: An early intervention for eating difficulties in patients with dementia can give them a better chance of maintaining independence and reduce the risk of malnutrition. METHODS: An experimental crossover design was employed. Twenty-nine residents were chosen from two dementia special care units in metropolitan Taipei. To avoid contamination between participants in units using both Montessori and control interventions, two dementia special care units were randomly assigned into Montessori intervention (I1) and routine activities (I2) sequence groups. A two period crossover design was used, with 15 residents assigned to Montessori intervention sequence I (I1, I2) and 14 residents assigned to Montessori intervention sequence II (I2, I1). On each intervention day, residents were given their assigned intervention. Montessori intervention was provided in 30-min sessions once every day, three days per week, for eight weeks. There was a two week washout period between each intervention. RESULTS: There was a significant reduction in the Edinburgh Feeding Evaluation in Dementia score for the Montessori intervention period but not for the routine activities period, while the mean differences for the Eating Behavior Scale score, self-feeding frequency and self-feeding time were significantly higher than those of the routine activities period. Except for the Mini-Nutritional Assessment score post-test being significantly less than the pre-test for the routine activities period, no significant differences for any other variables were found for the routine activities period. CONCLUSION: This study confirms the efficacy of a Montessori intervention protocol on eating ability of residents with dementia. Adopting Montessori intervention protocols to maintain residents' self-feeding ability in clinical practice is recommended. RELEVANCE TO CLINICAL PRACTICE: Montessori based activities could provide caregivers with an evidence-based nursing strategy to deal with eating difficulties of people with dementia. PMID- 21981706 TI - Commentary on Kilonzo B & O'Connell R (2011) Secondary prevention and learning needs post percutaneous coronary intervention (PCI): perspectives of both patients and nurses. Journal of Clinical Nursing 20, 1160-1167. PMID- 21981707 TI - DNA directed self-assembly of anisotropic plasmonic nanostructures. AB - Programmable positioning of one-dimensional (1D) gold nanorods (AuNRs) was achieved by DNA directed self-assembly. AuNR dimer structures with various predetermined inter-rod angles and relative distances were constructed with high efficiency. These discrete anisotropic metallic nanostructures exhibit unique plasmonic properties, as measured experimentally and simulated by the discrete dipole approximation method. PMID- 21981708 TI - Efficient throughput method for hygroscopicity classification of active and inactive pharmaceutical ingredients by water vapor sorption analysis. AB - The conventional method of hygroscopicity determination proposed by Callahan and co-workers utilizes more sample and time, may not be precise in all the cases, and is a relatively broader classification system. The method of indicating degree of hygroscopicity as per European Pharmacopoeia considers equilibration of sample for 24 hours under single humidity condition and may not necessarily ensure equilibration in all the cases. Additionally, both these methods do not provide information on solid state changes occurring within the sample during the course of experiment. This research work envisages an efficient throughput method for hygroscopicity determination, and validates it with active and inactive pharmaceutical ingredients using sorption analysis. Further, this method has been performed under optimal equilibration conditions, in a throughput manner (consuming less sample and time), with additional information on solid state changes occurring within the experimental conditions. This throughput method would be a valuable tool for hygroscopicity assessment of new chemical entities, during drug development in particular, and across all pharmaceutical materials in general. PMID- 21981709 TI - Transcriptional responses of surface water marine microbial assemblages to deep sea water amendment. AB - Deep-water nutrient injection in the North Pacific Subtropical Gyre provides an aperiodic yet significant source of inorganic nutrients to the nutrient-limiting surface waters, and has been implicated in phytoplankton bloom formation. Here we examined short-term transcriptional responses of surface water picoplankton assemblages in a deep-sea water (DSW) mixing experiment. Both flow cytometric and transcriptomic analysis indicated stimulation of an Alteromonas-like population in the DSW-amended treatment after 12 h, relative to the control. Among the highly expressed alteromonad transcripts in DSW-treated samples, those encoding genes associated with chemotaxis, cell motility and carbon metabolism were most highly represented, relative to the control. Similarly, Prochlorococcus showed significantly higher levels of transcripts associated with carbon fixation and photosynthesis, as well as slightly increased cell density, relative to the control. Although other microbial taxa did not exhibit enhanced growth, DSW stimulated changes in their genome-wide transcriptional profiles were still readily detectable. Cell-associated cyanophage DNA and cDNA profiles suggested DSW stimulation of phage-mediated cell lysis, in previously infected cells. Comparison of the DSW-responsive Alteromonas populations, to previously reported dissolved organic matter (DOM)-responding alteromonads (McCarren et al., 2010), revealed differential transcript abundances, predominantly among genes encoding mobile elements and phage-related genes. Transcript representation in other metabolic pathways differed significantly between Alteromonas populations in the two different treatments, suggesting perturbation-specific metabolic responses to DSW and DOM. In total, the results provide new insight into short-term responses of picoplankton to DSW mixing, which occur prior to the more well-studied, longer term growth responses of larger phytoplankton species. PMID- 21981711 TI - Correlation of tacrolimus levels in peripheral blood mononuclear cells with histological staging of rejection after liver transplantation: preliminary results of a prospective study. AB - Therapeutic drug monitoring of tacrolimus (TAC) is characterized by a complex relationship between trough blood TAC concentrations and therapeutic efficacy. This prospective study evaluates the predictive value of intrahepatic, peripheral blood mononuclear cells (PBMCs) and blood TAC concentrations during the early postliver transplantation (LT) period. In a cohort of 90 adult liver recipients under TAC-based monotherapy, liver biopsies were performed at day 7 post-LT, and PBMCs TAC concentrations were measured at day 1, 3, 5, and 7 post-LT. Both intrahepatic and PBMCs TAC concentrations were determined. All biopsies were graded following the Banff scoring. Intrahepatic, and day 3, 5, 7 PBMCs concentrations correlated very well with day 7 liver Banff rejection scores (P < 0.05). Clinical rejection was characterized by significantly lower mean TAC PBMCs concentrations at day 5 and 7 (P < 0.05) and tended to be associated to lower mean intrahepatic TAC concentrations at day 7 (P = 0.059). Intrahepatic TAC concentrations at day 7 significantly correlated with TAC PBMCs concentrations from day 5 post-LT (P < 0.05). TAC PBMCs concentrations might be reliable markers of immunosuppression efficacy during the early phase after LT. This finding could represent an additional tool to individualize more precisely early immunosuppressive schemes after liver transplantation. PMID- 21981710 TI - Absence of transfusion-associated microchimerism in pediatric and adult recipients of leukoreduced and gamma-irradiated blood components. AB - BACKGROUND: Transfusion-associated microchimerism (TA-MC), the persistence of significant levels of donor white blood cells (WBCs) in blood recipients for prolonged periods, has been demonstrated after nonleukoreduced and leukoreduced transfusion to patients with severe traumatic injury. Development of TA-MC has not been rigorously studied in settings that do not involve massive trauma where the blood is leukoreduced and irradiated. STUDY DESIGN AND METHODS: A cohort of 409 prospectively followed medical and surgical adult and pediatric female recipients of leukoreduced and mostly irradiated allogeneic red blood cell and platelet transfusions were evaluated to determine development of TA-MC. Four- and 8-weeks-posttransfusion samples were analyzed using quantitative real-time polymerase chain reaction for Y-chromosome sequences in WBC DNA, the marker for microchimeric cells in female blood recipients. Repeat testing was performed on Y chromosome-positive samples to confirm microchimerism (MC), and subsequent posttransfusion samples were tested to investigate persistence of MC. RESULTS: On initial testing, 40 of 207 (19%) adult and 44 of 202 (22%) pediatric female blood recipients demonstrated low-level MC. On repeat testing of these and additional specimens, 12 (3%) recipients demonstrated low-level transient MC, but none had persistent TA-MC similar to that seen in transfused trauma patients. CONCLUSION: Persistence of MC was not demonstrated in adult and pediatric recipients of leukoreduced and mostly irradiated blood components. The risk of TA-MC appears to be dependent on the clinical setting and is rare other than in patients sustaining severe traumatic injury. PMID- 21981712 TI - Co-oximetry in clinically healthy dogs and effects of time of post sampling on measurements. AB - OBJECTIVES: Co-oximetry is a complex and valuable laboratory method that measures haemoglobin species and oxygenation status by multi-wavelength spectrophotometry. The purpose of this study was to establish reference intervals for clinically healthy dogs and to determine the effect of time of analyses and sex of animals on the accuracy of results. METHODS: Blood was collected from 27 healthy adult dogs of various breeds and sex. Co-oximetry was performed on a CCX co-oximeter that measures eight haemoglobin and oxygen transport related parameters: carboxyhaemoglobin (COHb), deoxyhaemoglobin (HHb), oxyhaemoglobin (O(2)Hb), methaemoglobin (MetHb), total haemoglobin (tHb), oxygen saturation (SO(2)%), oxygen content (O(2)Ct) and oxygen capacity (O(2)Cap). RESULTS: Results obtained after 2 and 4 hours were not significantly different from those obtained immediately after sampling. But after 48 hours, the results for total haemoglobin, oxygen saturation, oxyhaemoglobin, oxygen content and oxygen capacity were significantly lower, and carboxyhaemoglobin and deoxyhaemoglobin values were significantly higher than determination immediately after sampling. Gender had no significant impact on co-oximetry values. CLINICAL SIGNIFICANCE: Co oximetry offers several advantages compared with other methods, including ease of use, increased accuracy and greater differentiation among haemoglobin species. PMID- 21981713 TI - Normolipidaemic xanthomatosis with systemic involvement of the skin, bone and pharynx. PMID- 21981714 TI - Discovery of a potent, selective, and orally available class I phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) kinase inhibitor (GDC-0980) for the treatment of cancer. AB - The discovery of 2 (GDC-0980), a class I PI3K and mTOR kinase inhibitor for oncology indications, is described. mTOR inhibition was added to the class I PI3K inhibitor 1 (GDC-0941) scaffold primarily through the substitution of the indazole in 1 for a 2-aminopyrimidine. This substitution also increased the microsomal stability and the free fraction of compounds as evidenced through a pairwise comparison of molecules that were otherwise identical. Highlighted in detail are analogues of an advanced compound 4 that were designed to improve solubility, resulting in 2. This compound, is potent across PI3K class I isoforms with IC(50)s of 5, 27, 7, and 14 nM for PI3Kalpha, beta, delta, and gamma, respectively, inhibits mTOR with a K(i) of 17 nM yet is highly selective versus a large panel of kinases including others in the PIKK family. On the basis of the cell potency, low clearance in mouse, and high free fraction, 2 demonstrated significant efficacy in mouse xenografts when dosed as low as 1 mg/kg orally and is currently in phase I clinical trials for cancer. PMID- 21981715 TI - Optimizing acidified bleach solutions to improve sporicidal efficacy on building materials. AB - AIMS: We evaluated whether lowering pH (with acetic acid) and raising free available chlorine (FAC) levels in bleach solutions would improve efficacy in inactivating Bacillus spores on different materials. We also determined how varying pH and FAC levels affected bleach stability. METHODS AND RESULTS: Acidified bleach solutions with pH levels of 4.5, 6 and 7.5 and FAC levels between 5000 and 10,000 ppm were evaluated for decontamination efficacy against Bacillus subtilis spores inoculated onto test coupons made from wood, ceramic and galvanized steel. Lowering the pH or increasing the FAC level improved efficacy in some of the tests, but depended on the material, which significantly affected decontamination efficacy. The acidified bleach at pH of 7.5 was significantly less effective than bleach at a pH of 4.5 or 6. The FAC levels in the bleach were the most stable at pH 4.5, and stability at pH 4.5 was not significantly affected by the initial FAC level. CONCLUSIONS: It may be advisable to use bleach solutions with lower pH (rather than high FAC levels) in light of both the decontamination efficacy and bleach stability results. For wood materials, use of sporicides other than acidified bleach may be warranted. SIGNIFICANCE AND IMPACT OF THE STUDY: These results may be useful in preparing acidified bleach solutions for decontamination of materials contaminated with spores such as Bacillus anthracis. PMID- 21981716 TI - Quality of sour cherry juice of different clones and cultivars (Prunus cerasus L.) determined by a combined sensory and NMR spectroscopic approach. AB - Juice was manufactured from seven different sour cherry clones/cultivars and evaluated by quantitative descriptive sensory analysis and (1)H NMR spectroscopy. The sensory evaluation showed a large variation in several sensory attributes between the sour cherry clones/cultivars, which could be divided into two groups on the basis of both the sensory data and the NMR spectroscopic data. These groups were closely related to the genetic background of the clones. Kelleris clones were distinctly different from Stevnsberry and Fanal clones. Hence, (1)H NMR spectroscopic data seem to correlate with sensory quality of different sour cherry clones. In addition, malic acid was the most important metabolite for modeling the two highly correlated sensory attributes sweetness and sourness, whereas the glucose content had a slight effect and the fructose content had no impact on sweetness/sourness. Other metabolites (ethyl acetate, asparagine, ethanol) could be correlated with sensory attributes; however, a direct causal connection could not be established. PMID- 21981717 TI - Investigative models in erectile dysfunction: a state-of-the-art review of current animal models. AB - INTRODUCTION: Erectile dysfunction (ED) is a common male sexual disorder producing a significant negative impact on the physical and psychosocial health of men and their partners. The development of ED is frequently attributable to both psychogenic factors as well as physiological alterations in neural, vascular, hormonal, and endothelial function. While the complex nature of human sexual function cannot possibly be replicated fully, the use of animal models provides a valid alternative to the investigation and evaluation of sexual dysfunction. AIM: To review the existing English literature pertaining to the use of experimental models (predominantly rodent models) for the evaluation of ED. MAIN OUTCOME MEASURES: Summary of relevant animal models of ED and the advantages and disadvantages of each animal model. METHODS: A Medline search using the key words "animal models of erectile dysfunction" was carried out and all relevant peer-reviewed English language was evaluated. RESULTS: While larger animals such as dogs, monkeys, cats, and rabbits were used in the early period of investigation (1960-1990), in recent times, rodents have largely replaced other animals as the predominant animal model for investigating erectile function. The most frequently reported models of ED can be classified as traumatic (cavernous nerve injury and arterial ligation) and metabolic (diabetic, hypercholesterolemia/lipidemia, and castration). Other models that have been studied include organic (smoking, hypertension, and chronic renal failure) and nonorganic (psychological) models. CONCLUSIONS: The development and utilization of the various rodent models has allowed for significant advances in the field of sexual dysfunction. Neurophysiological studies using the various animal models have provided important insights into human sexual dysfunction. At present, animal models play a significant role in evaluating novel therapeutics and surgical techniques and will likely continue to remain a vital research tool in the future. PMID- 21981718 TI - Innovative strategy for treatment of lung cancer: targeted nanotechnology-based inhalation co-delivery of anticancer drugs and siRNA. AB - A tumor targeted mesoporous silica nanoparticles (MSN)-based drug delivery system (DDS) was developed for inhalation treatment of lung cancer. The system was capable of effectively delivering inside cancer cells anticancer drugs (doxorubicin and cisplatin) combined with two types of siRNA targeted to MRP1 and BCL2 mRNA for suppression of pump and nonpump cellular resistance in non-small cell lung carcinoma, respectively. Targeting of MSN to cancer cells was achieved by the conjugation of LHRH peptide on the surface of MSN via poly(ethylene glycol) spacer. The delivered anticancer drugs and siRNA preserved their specific activity leading to the cell death induction and inhibition of targeted mRNA. Suppression of cellular resistance by siRNA effectively delivered inside cancer cells and substantially enhanced the cytotoxicity of anticancer drugs. Local delivery of MSN by inhalation led to the preferential accumulation of nanoparticles in the mouse lungs, prevented the escape of MSN into the systemic circulation, and limited their accumulation in other organs. The experimental data confirm that the developed DDS satisfies the major prerequisites for effective treatment of non-small cell lung carcinoma. Therefore, the proposed cancer-targeted MSN-based system for complex delivery of drugs and siRNA has high potential in the effective treatment of lung cancer. PMID- 21981719 TI - The endocytic uptake pathways of targeted toxins are influenced by synergistically acting Gypsophila saponins. AB - The expression of the epidermal growth factor (EGF) receptor is upregulated in many human tumors. We developed the targeted toxin SE, consisting of the plant toxin saporin-3 and human EGF. The cytotoxic effect of SE drastically increases in a synergistic manner by a combined treatment with Saponinum album (Spn), a saponin composite from Gypsophila paniculata L. Here we analyzed which endocytic pathways are involved in the uptake of SE and which are mandatory for the Spn mediated enhancement. We treated HER14 cells (NIH-3T3 cells transfected with human EGF receptor) with either chlorpromazine, dynasore, latrunculin A, chloroquine, bafilomycin A1 or filipin and analyzed the effect on the cytotoxicity of SE alone or in combination with Spn. We demonstrated that SE in combination with Spn enters cells via clathrin- and actin-dependent pathways and the acidification of the endosomes after endocytosis is relevant for the cytotoxicity of SE. Notably, our data suggest that SE without Spn follows a different endocytic uptake pathway. SE cytotoxicity is independent of blocking of clathrin or actin, and the decrease in endosomal pH is irrelevant for SE cytotoxicity. Furthermore, Spn has no influence on the retrograde transport. This work is important for the better understanding of the underlying mechanism of Spn enhanced cytotoxicity and helps to describe the role of Spn better. PMID- 21981720 TI - Explicitly correlated coupled cluster calculations for the benzenium ion (C6H7(+)) and its complexes with Ne and Ar. AB - Explicitly correlated coupled cluster theory at the CCSD(T)-F12x (x = a, b) level (Adler, T. B.; Knizia, G.; Werner, H.-J. J. Chem. Phys. 2007, 127, 221106) has been employed in a study of the benzenium ion (C6H7(+)) and its complexes with a neon or an argon atom. The ground-state rotational constants of C6H7(+) are predicted to be A0 = 5445 MHz, B0 = 5313 MHz, and C0 = 2731 MHz. Anharmonic vibrational wavenumbers of this cation were obtained by combination of harmonic CCSD(T*)-F12a values with anharmonic contributions calculated by double-hybrid density functional theory at the B2PLYP-D level. For the complexes of C6H7(+) with Ne or Ar, the lowest energy minimum is of pi-bonded structure. The corresponding dissociation energies D0 are estimated to be 160 and 550 cm(-1), respectively. There is no indication of H-bonds to the aromatic or aliphatic hydrogen atoms. Instead, three nonequivalent local energy minima were found for nuclear configurations where the rare-gas atom lies in the ring-plane and approximatly points to the center of one of the six CC bonds. PMID- 21981724 TI - Mortality rate and pattern following carbamate methomyl poisoning. Comparison with organophosphate poisoning of comparable toxicity. AB - CONTEXT: Methomyl is a widely used carbamate insecticide. It is known that mortality rate is generally low in carbamate poisoning, but fatalities from methomyl poisoning have been reported. Nevertheless, there is no reported comparative outcome of methomyl and organophosphate poisoning of comparable toxicity concerning mortality rate and mortality pattern. OBJECTIVE: This study aims to compare the mortality rate and pattern following methomyl poisoning with those after organophosphate poisoning of comparable toxicity. MATERIAL AND METHODS: A retrospective study was conducted on patients with cholinesterase inhibitor poisoning admitted to our institution. Among a diverse group of cholinesterase inhibitors, we included patients who presented after ingesting methomyl or World Health Organisation hazard Class I organophosphate compounds. Patients were divided into two groups; the methomyl group and the Class I organophosphate group. RESULTS: The methomyl group consisted of 17 patients, and the Class I organophosphate group consisted of 42 patients. Seven patients (41.2%) in the methomyl group presented with cardiac arrest, while none presented with cardiac arrest in the Class I organophosphate group (p < 0.001). In the methomyl group, patients who had not experienced cardiac arrest at presentation survived to discharge from hospital. Among the seven patients who presented with cardiac arrest, three died from multiple organ dysfunction syndrome after resuscitation from cardiac arrest. In the Class I organophosphate group, four patients died from pneumonia and complicating acute respiratory distress syndrome. Therefore, the mortality rate was 17.6% in the methomyl group and 9.5% in the Class I organophosphate group (p = 0.399). CONCLUSION: The mortality rate of methomyl poisoning was comparable to that of World Health Organisation Class I organophosphate poisoning. All died patients in the methomyl group experienced cardiac arrest, and died from multiple organ dysfunction syndrome after resuscitation from cardiac arrest. PMID- 21981725 TI - Mesh social networking: a patient-driven process. PMID- 21981726 TI - Validation of flow cytometric detection of platelet microparticles and liposomes by atomic force microscopy. AB - BACKGROUND: Platelet microparticles (PMPs) are a promising prognostic marker for thrombotic disorders because of their release during platelet activation. The use of flow cytometry for the enumeration of PMPs in plasma has generated controversy due to their size, which is below the stated detection limits of conventional flow cytometry instruments. The potential impact of this is an underestimation of PMP counts. OBJECTIVES/METHODS: To address this possibility, we used a combination of fluorescence-activated cell sorting (FACS) and atomic force microscopy (AFM) to determine the size distribution of PMPs present in plasma from acute myocardial infarction (AMI) patients and normal volunteers, and PMPs generated by expired platelet concentrates and washed platelets treated with agonists such as thrombin and calcium ionophore (A23187). RESULTS: According to AFM image analysis, there was no statistically significant difference in height or volume distributions in PMPs from thrombin-activated, calcium ionophore activated, expired platelet concentrates and plasma from healthy volunteers and AMI patients. Based on volume, expired platelets released the greatest proportion of exosomes (< 1.0 * 10(-22) L(3) in volume) in relation to the entire PMP population (29.7%) and the smallest proportion of exosomes was observed in AMI patient plasma (1.8%). Moreover, AFM imaging revealed that PMPs from expired platelets exhibited smooth surfaces compared with other PMP types but this was not statistically significant. CONCLUSIONS: We confirm that flow cytometry is capable of analyzing PMPs from plasma by using AFM to perform nanoscale measurements of individual PMP events isolated by FACS. This method also provided the first quantitative nanoscale images of PMP ultrastructure. PMID- 21981727 TI - Plasmonic imaging of human oral cancer cell communities during programmed cell death by nuclear-targeting silver nanoparticles. AB - Plasmonic nanoparticles (NPs) have become a useful platform in medicine for potential uses in disease diagnosis and treatment. Recently, it has been reported that plasmonic NPs conjugated to nuclear-targeting peptides cause DNA damage and apoptotic populations in cancer cells. In the present work, we utilized the plasmonic scattering property and the ability of nuclear-targeted silver nanoparticles (NLS/RGD-AgNPs) to induce programmed cell death in order to image in real-time the behavior of human oral squamous carcinoma (HSC-3) cell communities during and after the induction of apoptosis. Plasmonic live-cell imaging revealed that HSC-3 cells behave as nonprofessional phagocytes. The induction of apoptosis in some cells led to attraction of and their subsequent engulfment by neighboring cells. Attraction to apoptotic cells resulted in clustering of the cellular community. Live-cell imaging also revealed that, as the initial concentration of NLS/RGD-AgNPs increases, the rate of self-killing increases and the degree of attraction and clustering decreases. These results are discussed in terms of the proposed mechanism of cells undergoing programmed cell death. PMID- 21981729 TI - Uptake and translocation mechanisms of cationic amino derivatives functionalized on pristine C60 by lipid membranes: a molecular dynamics simulation study. AB - Bioactive molecules, cationic peptides among them, are nowadays well-recognized in modern pharmacology for their drug potential. However, they usually suffer from poor translocation across cell membranes, and specific drug carriers should be designed to circumvent this problem. In the present study, the uptake mechanism of fullerene bearing cationic ammonium groups by membranes modeled as lipid bilayers is investigated using extensive molecular dynamics simulations and free-energy calculations. Three main results issued from this work can be drawn. First, the fullerene core appears to be a good drug vector since it greatly enhances the uptake of the cationic groups by the membrane. Second, we show that the amino derivatives should be deprotonated at the lipid headgroup level in order to fully translocate the membrane by passive diffusion. Finally, the fullerenes bearing too many cationic groups display mostly a hydrophilic character; thus, the lipophilic fullerene core is not anymore effective as an insertion enhancer. Therefore, the lipid bilayer appears to be very selective with respect to the amount of amino groups conjugated with C(60). PMID- 21981728 TI - Gammaretroviral vector integration occurs overwhelmingly within and near DNase hypersensitive sites. AB - Concerns surrounding the oncogenic potential of recombinant gammaretroviral vectors has spurred a great deal of interest in vector integration site (VIS) preferences. Although gammaretroviral vectors exhibit a modest preference for integration near transcription start sites (TSS) of active genes, such associations only account for about a third of all VIS. Previous studies suggested a correlation between gammaretroviral VIS and DNase hypersensitive sites (DHS), which mark chromatin regions associated with cis-regulatory elements. In order to study this issue directly, we assessed the correlation between 167 validated gammaretroviral VIS and a deep genome-wide map of DHS, both determined in the same cell line (the human fibrosarcoma HT1080). The DHS map was developed by sequencing individual DNase I cleavage sites using massively parallel sequencing technologies. These studies revealed an overwhelming preference for integrations associated with DHS, with a median distance of only 238 bp between individual VIS and the nearest DHS for the experimental dataset, compared to 3 kb for a random dataset and 577 to 1457 bp for two unrelated cell lines (p<0.001). Indeed, nearly 84% of all VIS were found to be located within 1 kb of a DHS (p=10(-43)). Further, this correlation was statistically independent from the association with TSS. The preference for DHS far exceeds that seen for other hallmarks of gammaretroviral VIS, including TSS, and may help explain several aspects of gammaretroviral vector biology, including the mechanism of VIS selection, as well as the relative frequency and underlying biology of gammaretroviral vector-mediated genotoxicity. PMID- 21981730 TI - Transient storage of electrical charge in biofilms of Shewanella oneidensis MR-1 growing in a microbial fuel cell. AB - Current output of microbial fuel cells (MFCs) depends on a number of engineering variables mainly related to the design of the fuel cell reactor and the materials used. In most cases the engineering of MFCs relies on the premise that for a constant biomass, current output correlates well with the metabolic activity of the cells. In this study we analyze to what extent, MFC output is also affected by the mode of operation, emphasizing how discontinuous operation can affect temporal patterns of current output. The experimental work has been carried out with Shewanella oneidensis MR-1, grown in conventional two-chamber MFCs subject to periodic interruptions of the external circuit. Our results indicate that after closure of the external circuit, current intensity shows a peak that decays back to basal values. The result suggests that the MFC has the ability to store charge during open circuit situations. Further studies using chronoamperometric analyses were carried out using isolated biofilms of Shewanella oneidensis MR-1 developed in a MFC and placed in an electrochemistry chamber in the presence of an electron donor. The results of these studies indicate that the amount of excess current over the basal level released by the biofilm after periods of circuit disconnection is proportional to the duration of the disconnection period up to a maximum of approximately 60 min. The results indicate that biofilms of Shewanella oneidensis MR-1 have the ability to store charge when oxidizing organic substrates in the absence of an external acceptor. PMID- 21981731 TI - Predicting complex quantitative traits with Bayesian neural networks: a case study with Jersey cows and wheat. AB - BACKGROUND: In the study of associations between genomic data and complex phenotypes there may be relationships that are not amenable to parametric statistical modeling. Such associations have been investigated mainly using single-marker and Bayesian linear regression models that differ in their distributions, but that assume additive inheritance while ignoring interactions and non-linearity. When interactions have been included in the model, their effects have entered linearly. There is a growing interest in non-parametric methods for predicting quantitative traits based on reproducing kernel Hilbert spaces regressions on markers and radial basis functions. Artificial neural networks (ANN) provide an alternative, because these act as universal approximators of complex functions and can capture non-linear relationships between predictors and responses, with the interplay among variables learned adaptively. ANNs are interesting candidates for analysis of traits affected by cryptic forms of gene action. RESULTS: We investigated various Bayesian ANN architectures using for predicting phenotypes in two data sets consisting of milk production in Jersey cows and yield of inbred lines of wheat. For the Jerseys, predictor variables were derived from pedigree and molecular marker (35,798 single nucleotide polymorphisms, SNPS) information on 297 individually cows. The wheat data represented 599 lines, each genotyped with 1,279 markers. The ability of predicting fat, milk and protein yield was low when using pedigrees, but it was better when SNPs were employed, irrespective of the ANN trained. Predictive ability was even better in wheat because the trait was a mean, as opposed to an individual phenotype in cows. Non-linear neural networks outperformed a linear model in predictive ability in both data sets, but more clearly in wheat. CONCLUSION: Results suggest that neural networks may be useful for predicting complex traits using high-dimensional genomic information, a situation where the number of unknowns exceeds sample size. ANNs can capture nonlinearities, adaptively. This may be useful when prediction of phenotypes is crucial. PMID- 21981732 TI - Aerobic exercise and caloric reduction should be the key lifestyle modifications in obese patients with GERD. PMID- 21981734 TI - Medical therapy for primary sclerosing cholangitis. PMID- 21981736 TI - Thiopurine metabolites and TPMT activity measurement in inflammatory bowel disease. PMID- 21981738 TI - Lactose intolerance in inflammatory bowel disease. PMID- 21981739 TI - Association of lactose sensitivity with inflammatory bowel disease. PMID- 21981741 TI - Leukemia and lymphoma incidence in children in Alberta, Canada: a population based 22-year retrospective study. AB - There is a paucity of published literature on the epidemiology of childhood acute leukemias and lymphomas in Canada. This study was designed to describe children and youth (age <20 years) diagnosed with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) in Alberta, Canada, during 22 fiscal years. The Alberta Cancer Registry was used to extract data all ALL, AML, HL, and NHL cases diagnosed between April 1, 1982, and March 31, 2004. Population data for Alberta were also obtained. Descriptive statistics and cluster detection tests were used. During 22 years, 525, 117, 257, and 111 children (total = 1010) were diagnosed with ALL, AML, HL, and NHL, respectively. The median ages at diagnosis were 4, 11, 16, and 12 years for ALL, AML, HL, and NHL, respectively. The majority were male for ALL (287/525, 55%), AML (64/117, 55%), and NHL (81/111, 73%), and female for HL (133/257, 52%). The crude rates per 100,000 children were variable, without significant trends, over time and for each diagnosis; the median annual rates, per 100,000 children, were 3.00 (ranging from 1.87 to 3.75) for ALL, 0.62 (ranging from 0.26 to 1.27) for AML, 1.42 (ranging from 0.76 to 2.67) for HL, and 0.54 (ranging from 0.24 to 1.40) for NHL. A few potential spatiotemporal clusters were identified. They are likely due to small number of cases and plausibly clinically insignificant. Overall, childhood leukemia and lymphoma rates in Alberta have remained relatively stable, with no clear epidemiological trends and no significant spatiotemporal clustering. Further investigations are warranted to see if such stability continues and if spatiotemporal patterns arise from longer studies and studies in larger geographic regions with a larger sample size, whilst analyzing for other causal/associated factors, individual susceptibilities, and disease outcomes. PMID- 21981742 TI - Synergistic metabolism of a broad range of C1 compounds in the marine methylotrophic bacterium HTCC2181. AB - The 1.3 Mbp genome of HTCC2181, a member of the abundant OM43 clade of coastal bacterioplankton, suggested it is an obligate methylotroph. Preliminary experiments demonstrated that methanol and formaldehyde, but not other common C1 compounds such as methylamine, could support growth. Methanol concentrations in seawater are reportedly < 100 nM, suggesting either that the flux of methanol through plankton pools is very rapid, or that methanol may not be the primary growth substrate for HTCC2181. Therefore, we investigated the apparent extreme substrate range restriction of HTCC2181 in greater detail. Growth rate and maximum cell density of HTCC2181 increased with methanol concentration, yielding a K(s) value of 19 uM. In contrast, no growth was observed in the presence of the methylated (C1) compounds, methyl chloride, trimethylamine-oxide (TMAO) or dimethylsulfoniopropionate (DMSP) when they were the sole substrates. However, growth rate, maximum cell density and cellular ATP content were significantly enhanced when any of these methylated compounds were provided in the presence of a limiting concentration of methanol. These observations fit a model in which the metabolic intermediate formaldehyde is required for net carbon assimilation, allowing C1 substrates that do not produce a formaldehyde intermediate to be oxidized for energy, but not assimilated into biomass. Rates of methanol and TMAO oxidation and assimilation were measured with (14)C-radiolabelled compounds in cultures of HTCC2181 and seawater microbial communities collected off the Oregon coast. The results indicated that in nature as well as in culture, C1 substrates are partitioned between those that are mainly oxidized to produce energy and those that are assimilated. These findings indicate that the combined fluxes of C1 compounds in coastal systems are sufficient to support significant populations of obligate methyltrophs by a metabolic strategy that involves the synergistic metabolism of multiple C1 compounds. PMID- 21981743 TI - Efficacy of low-dose methotrexate in the treatment of dermatomyositis skin lesions. AB - A limited number of case series has indicated that methotrexate (MTX) might be a useful drug in the treatment of dermatomyositis (DM), a rare autoimmune disease involving the skin and muscles. However, these earlier studies mainly focused on the efficacy of MTX on DM muscular symptoms. To analyse the efficacy of MTX on skin lesions in DM, the records of 34 patients with DM seen between 2004 and 2009 were retrospectively analysed, and the DM skin disease activity at different time points was determined, with specific focus on cutaneous features using the validated Cutaneous Dermatomyositis Activity Index (CDASI) score. The lesional inflammation was scored in primary skin biopsies. Additionally, we performed a systematic review of the available literature. In our series, 11 patients with DM received MTX, and in 8 of them, MTX led to a significant reduction of the DM skin lesions. CDASI scores decreased from 15.7 to 6.4 (P < 0.01) within 2-3 months, supporting the effectiveness of MTX in skin disease in DM. The lymphocytic infiltrate in primary skin lesions of MTX responders was significantly more pronounced than that in nonresponders. These results indicate that MTX might be an effective drug to treat the cutaneous symptoms of DM, as measured by the validated CDASI. Interestingly, MTX responders histologically presented a significantly stronger lesional lymphocytic inflammatory infiltrate than did nonresponders. These findings suggest that the functional inhibition of lymphocyte migration in the skin might be an important mechanism of MTX in the treatment of DM. PMID- 21981744 TI - Minimal clinically important differences in the vaginal insertion and successful intercourse items of the sexual encounter profile. AB - INTRODUCTION: Despite adoption of the successful vaginal insertion (Q2) and intercourse (Q3) items of the sexual encounter profile (SEP) as end points in clinical trials, there are no objective data on what constitute minimal clinically important differences (MCIDs) in these items. AIM: The objective was to estimate the MCID for SEP Q2 and Q3. METHODS: Using data from 17 randomized, controlled trials of the phosphodiesterase type 5 inhibitor tadalafil, we estimated MCIDs for the SEP using anchor-based approaches. The 17 studies included 3,345 patients treated for 12 weeks. The anchor for the MCID is the minimal improvement measure calculated using change from baseline to 12 weeks on the following question: "Over the past 4 weeks, when you attempted sexual intercourse how often was it satisfactory for you?" MCIDs were developed using analysis of variance- and receiver operating characteristic (ROC)-based methods in a subset of studies (N = 11) by comparing patients with and without minimal improvement (N = 863). MCIDs were validated in the remaining six studies (N = 377). MAIN OUTCOME MEASURES: The main outcome measures of this study are SEP Q2 and Q3. RESULTS: Using the ROC-based approach, the MCID for SEP Q2 was 21.4%, with estimated sensitivity of 0.55 and specificity of 0.73; the MCID for SEP Q3 was 23.0%, with estimated sensitivity of 0.72 and specificity of 0.78. MCIDs for SEP Q2/Q3 varied significantly (P < 0.001) according to baseline erectile dysfunction (ED) severity. MCIDs distinguished between patients in the validation sample classified as no change or minimally improved in each ED etiology, ED duration, and age group, but less well across geographic regions. CONCLUSIONS: The contextualization of treatment-related changes into clinically relevant terms is essential to understanding treatment efficacy, interpreting results across studies, and for effective patient management. Overall, there was a better balance between sensitivity and specificity of the MCIDs using the ROC-based approach for the SEP intercourse success item than for the vaginal insertion item. PMID- 21981745 TI - Utilizing the media to help increase organ donation in the Hispanic American population. AB - OBJECTIVE: As the shortage of suitable organs for transplantation is especially pronounced among Hispanic Americans (HA), our objective was to determine whether a focused media campaign including culturally sensitive educational material on organ donation would positively influence organ donation awareness, perceptions, and beliefs, and increase the likelihood of organ donation in the HA community. METHODS: Cross-sectional telephone surveys were conducted before and after a media campaign in four Southern California neighborhoods with a high percentage of HA. Respondents, age >=18 yr, were drawn randomly from lists of Hispanic surnames. Awareness, perception, and belief regarding organ donation and intent to-donate were measured. The differences between the Pre- and Post-media surveys were analyzed. RESULTS: A total of 524 Pre-media and 528 Post-media subjects were evaluated. The Post-media surveys demonstrated improvements in: organ donation awareness (43% vs. 31%, p < 0.0001), the belief that donation is a social responsibility (54% vs. 45%, p = 0.008), and the belief that donation helps people (91% vs. 87%, p = 0.09). CONCLUSIONS: A media campaign emphasizing culturally sensitive educational material can significantly influence organ donation awareness and beliefs in HA. PMID- 21981746 TI - Comparative phylogeography reveals a shared impact of pleistocene environmental change in shaping genetic diversity within nine Anopheles mosquito species across the Indo-Burma biodiversity hotspot. AB - South-East Asia is one of the world's richest regions in terms of biodiversity. An understanding of the distribution of diversity and the factors shaping it is lacking, yet essential for identifying conservation priorities for the region's highly threatened biodiversity. Here, we take a large-scale comparative approach, combining data from nine forest-associated Anopheles mosquito species and using statistical phylogeographical methods to disentangle the effects of environmental history, species-specific ecology and random coalescent effects. Spatially explicit modelling of Pleistocene demographic history supports a common influence of environmental events in shaping the genetic diversity of all species examined, despite differences in species' mtDNA gene trees. Populations were periodically restricted to allopatric northeastern and northwestern refugia, most likely due to Pleistocene forest fragmentation. Subsequent southwards post-glacial recolonization is supported by a north-south gradient of decreasing genetic diversity. Repeated allopatric fragmentation and recolonization have led to the formation of deeply divergent geographical lineages within four species and a suture zone where these intraspecific lineages meet along the Thai-Myanmar border. A common environmental influence for this divergence was further indicated by strong support for simultaneous divergence within the same four species, dating to approximately 900 thousand years ago (kya). Differences in the geographical structuring of genetic diversity between species are probably the result of varying species' biology. The findings have important implications for conservation planning; if the refugial regions and suture zone identified here are shared by other forest taxa, the unique and high levels of genetic diversity they house will make these areas conservation priorities. PMID- 21981747 TI - Making an offer you can't refuse? A challenge of altruistic donation. AB - Living donation is becoming increasingly used to help fill the gap between the needs of potential organ recipients and the availability of organs from deceased donors. The last few years has seen a small, but increasing contribution from altruistic (or good Samaritan or nondirected) donors. However, use of organs from such donors is associated with ethical as well as practical issues. The rights of the well-informed and consented donor to donate must be balanced against the rights of the surgeons to decline to offer such a service. PMID- 21981748 TI - Full-mouth rehabilitation of a patient with severely worn dentition and uneven occlusal plane: a clinical report. AB - Severe tooth wear is frequently multifactorial and variable. Successful management is a subject of interest in dentistry. A critical aspect is to determine the occlusal vertical dimension (OVD) and a systematic approach that can lead to a predictable and favorable treatment prognosis. Management of patients with worn dentition is complex and difficult. Accurate clinical and radiographic examinations, a diagnostic wax-up, and determining OVD are crucial. Using mini-implants as orthodontic anchorage may facilitate orthodontic movement of teeth to improve their position, which is necessary for favorable prosthetic treatment. A 46-year-old man was referred for restoration of his worn and missing teeth. After diagnostic work-up, provisional removable prostheses were fabricated for both jaws, evaluated clinically, and adjusted according to esthetic, phonetic, and vertical dimension criteria. Clinical crown lengthening and free gingival graft procedures were performed in appropriate areas. Drifting of the left posterior mandibular teeth was corrected using mini-implants as orthodontic anchorage. Two conventional implants were inserted in the right mandibular edentulous area. After endodontic therapy of worn teeth, custom-cast gold dowels and cores were fabricated, and provisional removable prostheses were replaced with fixed provisional restorations. Metal-ceramic restorations were fabricated, and a removable partial denture with attachments was fabricated for maxillary edentulous areas. An occlusal splint was used to protect the restorations. Full mouth rehabilitation of the patient with severely worn dentition and an uneven occlusal plane was found to be successful after 3 years of follow-up. This result can encourage clinicians to seek accurate diagnosis and treatment planning to treat such patients. PMID- 21981749 TI - Additive value of adult bone-marrow-derived cell transplantation to conventional revascularization in chronic ischemic heart disease: a systemic review and meta analysis. AB - OBJECTIVE: Whether adult bone marrow (BM)-derived cells (BMCs) transplantation benefits patients with chronic ischemic heart disease (IHD) remains controversial. This systemic and meta-analysis study aimed to assess the potential therapeutic effects of BMCs transplantation with revascularization in chronic IHD. RESEARCH DESIGN AND METHODS: Randomized controlled trials of BMCs in combination with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) for chronic IHD were identified by searching Medline, Embase, the Cochrane Controlled Trials Register, the Cochrane Library, and the Web of Science. We conducted a random-effects meta-analysis across eligible studies measuring the same outcomes. RESULTS: Ten randomized controlled trials including 422 participants were reviewed. In the trials with six months of follow-up, BMCs transplantation improved left ventricular (LV) ejection fraction (LVEF) by 4.02% and reduced LV end-systolic and end-diastolic volumes. Subgroup analysis revealed a statistically significant difference in LVEF associated with primary intervention, route of cell delivery, cell type, and baseline LVEF, but not with cell dose or storage duration. CONCLUSIONS: Selected-BMCs transplantation through myocardial injection after surgical revascularization may benefit patients with chronic IHD and severely impaired LV function. Due to the limitation of patient number, RCT with larger sample size and long follow-up are required for future research. PMID- 21981750 TI - Natural anti-A and anti-B of the ABO system: allo- and autoantibodies have different epitope specificity. AB - BACKGROUND: According to Landsteiner's law, alloantibodies are prevalent and autoantibodies are absent in the ABO blood group system. However, one study (Spalter et al., Blood 1999;93:4418-24) has suggested that low-affinity ABO autoantibodies, mitigated by anti-idiotypic immunoglobulins are also prevalent, while another publication (Rieben et al., Eur J Immunol 1992;22:2713-7) shows that humans do not have B-lymphocytes capable of producing immunoglobulin G ABO autoantibodies. STUDY DESIGN AND METHODS: We used hapten-specific chromatography to isolate allo- and autoantibodies from pools of A or B serum and then characterized the resultant antibodies against a wide range of ABO and related glycoconjugates. RESULTS: We found that the apparent autoantibodies are directed against blood group A or B disaccharides, without consideration for the presence of fucose, but requiring the absence of elongating sugar X in composition of Gal(NAc)alpha1-3(Fucalpha1-2)Galbeta1-X-terminated carbohydrate chain. In contrast, ABO alloantibodies required a minimum trisaccharide Gal(NAc)alpha1 3(Fucalpha1-2)Gal epitope and recognize the elongated type-specific tetrasaccharides. Furthermore, alloantibodies appear to be a small set of specific yet crossreactive antibodies that detect all backbone types of A or B antigens, rather than being a collection of specific antibodies, each of which detects a different type of A or B antigen. CONCLUSION: Apparent ABO autoantibodies appear to have no natural human target. PMID- 21981751 TI - Cr3+-doped fluorides and oxides: role of internal fields and limitations of the Tanabe-Sugano approach. AB - This work is aimed at clarifying the changes on optical spectra of Cr(3+) impurities due to either a host lattice variation or a hydrostatic pressure, which can hardly be understood by means of the usual Tanabe-Sugano (TS) approach assuming that the Racah parameter, B, grows when covalency decreases. For achieving this goal, the optical properties of Cr(3+)-doped LiBaF(3) and KMgF(3) model systems have been explored by means of high level ab initio calculations on CrF(6)(3-) units subject to the electric field, E(R)(r), created by the rest of the lattice ions. These calculations, which reproduce available experimental data, indicate that the energy, E((2)E), of the (2)E(t(2g)(3)) -> (4)A(2)(t(2g)(3)) emission transition is nearly independent of the host lattice. By contrast, the energy difference corresponding to (4)A(2)(t(2g)(3)) -> (4)T(1)(t(2g)(2)e(g)(1)) and (4)A(2)(t(2g)(3)) -> (4)T(2)(t(2g)(2)e(g)(1)) excitations, Delta((4)T(1); (4)T(2)), is shown to increase on passing from the normal to the inverted perovskite host lattice despite the increase in covalency, a fact which cannot be accounted for through the usual TS model. Similarly, when the Cr(3+)-F(-) distance, R, is reduced both Delta((4)T(1); (4)T(2)) and the covalency are found to increase. By analyzing the limitations of the usual model, we found surprising results that are shown to arise from the deformation of both 3d(Cr) and ligand orbitals in the antibonding e(g) orbital, which has a sigma character and is more extended than the pi t(2g) orbital. By contrast, because of the higher stiffness of the t(2g) orbital, the dependence of E((2)E) with R basically follows the corresponding variation of covalency in that level. Bearing in mind the similarities of the optical properties displayed by Cr(3+) impurities in oxides and fluorides, the present results can be useful for understanding experimental data on Cr(3+)-based gemstones where the local symmetry is lower than cubic. PMID- 21981752 TI - Using absorption simulation and gastric pH modulated dog model for formulation development to overcome achlorhydria effect. AB - Impaired absorption of weakly basic drugs in patients with reduced gastric acidity can lead to loss of efficacy of the therapeutic agent. Hence, a robust formulation which can provide adequate exposure in achlorhydric patients is imperative to achieve the desired efficacy. In this report, formulation development of a weakly basic Merck compound A is described. Compound A shows lower solubility at higher pH and thus is prone to reduced exposure under conditions of achlorhydria, as the compound's solubility increases only in environments of less than pH 2. Several formulations with or without an acidifier were developed and characterized by in vitro dissolution and in gastric pH modified dog model to assess their bioperformance in high gastric pH conditions. To predict the bioperformance of these formulations in humans, a dissolution based absorption model was developed and validated against the observed PPI interaction data in the clinic and the gastric pH-adjusted dog data. An additional absorption model was developed to allow for incorporation of the dog PK data to provide translation of preclinical to clinical exposure. Based on the in vitro dissolution, in silico absorption modeling and preclinical in vivo data, a citric acid-based formulation (F2) was selected for a human pharmacokinetic study. This study showed that exposures from F2 were not meaningfully different in the presence of proton pump inhibitor (PPI) as compared to non-PPI, thus confirming that the F2 formulation was successful in overcoming the achlorhydria effect. These efforts also highlighted that the complementary use of in vitro/in silico/in vivo (IVISIV) tools may be a helpful strategy in the development of formulations to overcome the achlorhydria effect and achieve adequate exposure in patients with high gastric pH. PMID- 21981754 TI - Can primary care data be used to monitor regional smoking prevalence? An analysis of The Health Improvement Network primary care data. AB - BACKGROUND: Accurate and timely regional data on smoking trends allow tobacco control interventions to be targeted at the areas most in need and facilitate the evaluation of such interventions. Electronic primary care databases have the potential to provide a valuable source of such data due to their size, continuity and the availability of socio-demographic data. UK electronic primary care data on smoking prevalence from The Health Improvement Network (THIN) have previously been validated at the national level, but may be less representative at the regional level due to reduced sample sizes. We investigated whether this database provides valid regional data and whether it can be used to compare smoking prevalence in different UK regions. METHODS: Annual estimates of smoking prevalence by government office region (GOR) from THIN were compared with estimates of smoking prevalence from the General Lifestyle Survey (GLF) from 2000 to 2008. RESULTS: For all regions, THIN prevalence data were generally found to be highly comparable with GLF data from 2006 onwards. CONCLUSIONS: THIN primary care data could be used to monitor regional smoking prevalence and highlight regional differences in smoking in the UK. PMID- 21981753 TI - The effect of internal marketing on job satisfaction in health services: a pilot study in public hospitals in Northern Greece. AB - BACKGROUND: The purpose of this study was to explore the effect of internal marketing on job satisfaction in health services, particularly in public hospitals in Northern Greece. METHODS: A questionnaire with three sections was used. The first one referred to internal marketing by using Foreman and Money's scale, while the second one contained questions on job satisfaction based on Stamps and Piermonte's work. The last section included demographic questions. Three categories of health care professionals, nurses, doctors and paramedic personnel working in public hospitals have participated. RESULTS: Doctors tend to be more satisfied with their job than nurses in the same hospitals. Male personnel also tend to be more satisfied with their job than female. Time-defined work contract personnel have a greater level of job satisfaction than permanent personnel. Marital status, position, and educational level have no statistically significant impact on job satisfaction. A slight decline in job satisfaction occurs as the personnel age. CONCLUSIONS: Internal marketing has a positive effect on the job satisfaction of hospital staff in Northern Greece. Also, doctors and male personnel seem to have greater levels of job satisfaction. Staff with time-defined work contracts with the hospital are more satisfied than permanent staff, and as the staff age, there is a slight decline in job satisfaction. PMID- 21981755 TI - Incidence of malocclusion between primary and mixed dentitions among Brazilian children. A 5-year longitudinal study. AB - OBJECTIVE: To determine the incidence of malocclusion in a 5-year follow-up of school children and verify the hypothesis that individuals with previous malocclusion are more prone to maintain the same characteristics in the transition from primary to mixed dentition. MATERIALS AND METHODS: School children, ages 8 to 11 years, participated. Inclusion criteria consisted of normal occlusion in primary dentition or subsequent malocclusions, anterior open bite and/or posterior crossbite and/or overjet measuring more than 3 mm, and that subjects had not submitted to orthodontic treatment and adenoidectomy. Data collection was based on evaluation of occlusion in school children in the actual stage of mixed dentition. Descriptive, Chi-square, and relative risk (RR) 95% confidence interval (CI) analyses were carried out. RESULTS: The greatest incidence of malocclusion was found in children with malocclusion (94.1%) when compared with those without malocclusion (67.7%) (RR = 1.4 [1.2-1.6]; P < .001). Anterior open bite (RR = 3.1 [1.7-5.8]), posterior crossbite (RR = 7.5 [4.9-11.5]), and overjet greater than 3 mm (RR = 5.2 [3.4-8.0]) in the primary dentition are risk factors for malocclusion in early mixed dentition. Spontaneous correction of the anterior open bite was confirmed in 70.1% of cases. Posterior crossbite and overjet greater than 3 mm were persistent in 87.8% and 72.9% of children. CONCLUSIONS: Malocclusion incidence was high. Individuals with previous anterior open bite, greater overjet, and posterior crossbite had greater risk of having the same characteristics in the mixed dentition. PMID- 21981756 TI - Methoxetamine: a novel ketamine analog and growing health-care concern. PMID- 21981757 TI - The antibody response to an HLA mismatch: a model for nonself-self discrimination in relation to HLA epitope immunogenicity. AB - Antibodies to HLA mismatches are specific for epitopes rather than antigens. HLAMatchmaker considers each HLA antigen as a string of eplets that represent key elements of epitopes. Certain antibodies are specific for single eplets, but recent studies have demonstrated that epitopes defined by eplet pairs always involve one nonself-eplet and a self-eplet shared between the immunizing antigen and the antibody producer. This suggests an autoreactive component of the alloantibody response to an HLA mismatch and this report expands this concept. During B-cell development, V(H) and V(L) gene rearrangements produce a diversity of Ig receptors that can recognize epitopes on autologous proteins. It is hypothesized that B cells carry low-affinity receptors for self-HLA antigens. Their interactions with self-HLA proteins will not lead to B-cell activation or antibody production. In contrast, exposure to HLA mismatches induces often strong alloantibody responses. The activation of self-HLA-specific B cell by a nonself eplet may require that the remainder of the structural epitope of the immunizing antigen has considerable structural similarity with one of the antibody producer's alleles. This hypothesis has been tested in molecular modelling studies with six epitopes defined by human monoclonal antibodies. In each case, one allele of the antibody producer had no or few differences with the immunizing allele in antibody-accessible positions defined by a 15 Angstrom radius of the mismatched eplet. The other alleles of the antibody producer showed significantly greater numbers of residue differences with the immunizer (5.8 +/- 2.0 versus 1.0 +/- 0.6, P < 0.0001). These data support the concept that HLA antibodies originate from B cells with self-HLA immunoglobulin receptors that recognize mismatched eplets as nonself entities on immunizing antigens. The nonself-self paradigm provides a new insight of HLA epitope immunogenicity and may explain why sensitized patients have antibodies to a restricted number of mismatched epitopes. PMID- 21981758 TI - Differential brain responses to social exclusion by one's own versus opposite gender peers. AB - Human peer relations provide tangible benefits, including food and protection, as well as emotional benefits. While social exclusion poses a threat to all of these benefits, the psychological threat is particularly susceptible to modulation by the relation of the excluders to the excluded person. The current study used functional magnetic resonance imaging to explore the effects of manipulating the gender relation of participants to their excluders during an interactive ball toss game. Ventral anterior cingulate cortex activation was higher during exclusion by same-gender peers, while right ventrolateral prefrontal cortex activation negatively correlated with self-reported distress in other-gender exclusion. Results imply that exclusion by one's own gender is fundamentally different from exclusion by the opposite gender, and suggest a regulatory role for ventrolateral prefrontal cortex in response to out-group exclusion. Individual differences in implicit gender attitudes modulated neural responses to exclusion. The importance of these findings to investigations of social cognition is discussed. PMID- 21981759 TI - High cytoplasmic expression of p27(Kip1) is associated with a worse cancer specific survival in clear cell renal cell carcinoma. AB - What's known on the subject? and What does the study add? The loss of p27(Kip1) correlates with poor prognosis in various human cancers, and was postulated as a biomarker in RCC. Up to now p27(Kip1) analysis in RCC was focused on its nuclear localization. We confirmed higher p27(Kip1) expression in the nucleus and cytoplasm of RCC and correlated high cytoplasmic p27(Kip1) with an unfavourable clinic and a reduced survival. OBJECTIVES: To analyse the cytoplasmic and nuclear differences of p27(Kip1) expression and localization in benign and clear cell renal cell carcinoma (ccRCC) with regard to overall survival (OS) and cancer specific survival (CSS). p27(Kip1) is considered to contribute to the progression of ccRCC and is targeted by next generation dual-therapies. PATIENTS AND METHODS: In 140 patients, ccRCC and corresponding benign kidney tissue were analyzed for nuclear and cytoplasmic staining of p27(Kip1) by immunohistochemistry using a tissue microarray technique. Staining intensity and percentage of positive stained cells are given as expression scores. p27(Kip1) expression was categorized as high if ccRCC tissue stained stronger than the respective level of the corresponding benign tissue and categorized as low if ccRCC tissue stained less than or equal to the corresponding benign tissue. Differences in OS and CSS were analyzed by log-rank analysis and expression levels were correlated with tumour and patient characteristics using Fisher's exact test. RESULTS: Cytoplasmatic (mean [sd]: 13.8% [1.2%] vs 10.7% [1.7%]; P= 0.04) and nuclear (mean [sd]: 75.6% [2.7%] vs 13.6% [2.1%]; P < 0.001) staining of p27(Kip1) were significantly stronger in ccRCC tissues compared to benign tissue. High cytoplasmic p27(Kip1) expression was significantly associated with a higher T and N stage, Fuhrman grade and the presence of metastatic disease (P < 0.001). The median follow-up time was 38.2 months. There was no difference in OS between the low and high expression groups, although CSS was significantly lower in patients with high cytoplasmic p27(Kip1) (P < 0.001) and CSS heavily tended to be lower in the nuclear low expression group (P= 0.069). CONCLUSIONS: High cytoplasmic p27(Kip1) levels in renal cancer tissues are associated with advanced disease and reduced cancer specific survival, whereas low nuclear expression levels appear to be beneficial. The present study corroborates the consideration of cytoplasmic p27(Kip1) for future diagnostic and targeted therapeutic approaches in RCC establishing a potential protective shift of p27(Kip1) from the cytoplasm to the nucleus. PMID- 21981760 TI - Generation of CD34+ cells from CCR5-disrupted human embryonic and induced pluripotent stem cells. AB - C-C chemokine receptor type 5 (CCR5) is a major co-receptor for the entry of human immunodeficiency virus type-1 (HIV-1) into target cells. Human hematopoietic stem cells (hHSCs) with naturally occurring CCR5 deletions (Delta32) or artificially disrupted CCR5 have shown potential for curing acquired immunodeficiency syndrome (AIDS). However, Delta32 donors are scarce, heterologous bone marrow transplantation is not exempt of risks, and genetic engineering of autologous hHSCs is not trivial. Here, we have disrupted the CCR5 locus of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) using specific zinc finger nucleases (ZFNs) combined with homologous recombination. The modified hESCs and hiPSCs retained pluripotent characteristics and could be differentiated in vitro into CD34(+) cells that formed all types of hematopoietic colonies. Our results suggest the potential of using patient specific hHSCs derived from ZFN-modified hiPSCs for treating AIDS. PMID- 21981761 TI - Attitudes of qualified vs. student mental health nurses towards an individual diagnosed with schizophrenia. AB - AIM: This paper is the report of a study which sought to compare the attitudes held by student and qualified mental health nurses towards individuals with schizophrenia in the Republic of Ireland. BACKGROUND: Media portrayals of individuals with schizophrenia often include images of aggression and violence. With global initiatives aimed at reducing the stigma and exclusion associated with mental illness, the attitudes of those who care for people with schizophrenia are of particular interest. METHODS: A survey was administered to 66 student mental health nurses, and 121 qualified mental health nurses. Participants completed the community attitudes to mental illness scale and the social interaction scale in 2009. Multivariate analysis of variance was used to test for the effects of qualification, work setting, years of experience and education on the measures. RESULTS: Nurses employed in a community setting held more positive attitudes, when compared with colleagues who worked in an inpatient setting, as measured by the community mental health ideology subscale, indicating their desire to promote community care for individuals with schizophrenia. Nurses working in an inpatient setting held more socially restrictive attitudes indicating that they felt individuals with schizophrenia were dangerous and should be avoided. These findings were statistically significant at the P < 0.05 level. CONCLUSIONS: Mental health nurses must be alerted to the fact that holding negative attitudes may adversely affect the therapeutic relationship and ultimately lead to stigmatization and its negative consequences. PMID- 21981762 TI - Differences in phenotype and disease course in adult and paediatric inflammatory bowel disease--a population-based study. AB - BACKGROUND: Few studies have compared phenotype and disease course in children and adults with inflammatory bowel disease (IBD). AIM: To compare phenotype, treatment and disease course in children (<15 years) and adults (>=18 years) with IBD. METHODS: Two population-based cohorts comprising paediatric (2001-2006) and adult (2003-2004) patients from Copenhagen County and City were studied. RESULTS: Twenty children and 106 adults with ulcerative colitis (UC), and 29 children and 67 adults with Crohn's disease (CD) were included. Median follow-up time was 4.8 years (children) and 5.2 years (adults). Children with UC had more extensive disease compared to adult patients [14 (70%) vs. 20 (19%), P<0.001]. The risks of starting systemic steroid treatment and AZA/MP were higher for paediatric UC patients compared to adult UC patients; hazard ratio (HR): 3.1 (95% CI: 1.8-5.3) and HR: 2.5 (1.3-5-9), respectively. Steroid dependency was more frequent in paediatric than in adult UC patients [9 (45%) vs. 9 (8%), P<0.001]. Mild disease course was less frequent in children with UC compared to adult patients [7 (35%) vs. 76 (72%), P=0.002]. Paediatric and adult CD patients did not differ regarding treatment or disease course. Cumulative 5-year surgery rates for paediatric and adult patients were 5% and 9% for UC (N.S.) and 18% and 21% for CD (N.S.), respectively. CONCLUSIONS: Paediatric UC patients had more extensive disease, were more often treated with systemic steroids and AZA, had a higher frequency of steroid dependency and a more severe disease course compared to adult UC patients. No differences were found when comparing paediatric and adult CD patients. PMID- 21981763 TI - Activation of alpha-keto acid-dependent dioxygenases: application of an {FeNO}7/{FeO2}8 methodology for characterizing the initial steps of O2 activation. AB - The alpha-keto acid-dependent dioxygenases are a major subgroup within the O(2) activating mononuclear nonheme iron enzymes. For these enzymes, the resting ferrous, the substrate plus cofactor-bound ferrous, and the Fe(IV)?O states of the reaction have been well studied. The initial O(2)-binding and activation steps are experimentally inaccessible and thus are not well understood. In this study, NO is used as an O(2) analogue to probe the effects of alpha-keto acid binding in 4-hydroxyphenylpyruvate dioxygenase (HPPD). A combination of EPR, UV vis absorption, magnetic circular dichroism (MCD), and variable-temperature, variable-field (VTVH) MCD spectroscopies in conjunction with computational models is used to explore the HPPD-NO and HPPD-HPP-NO complexes. New spectroscopic features are present in the alpha-keto acid bound {FeNO}(7) site that reflect the strong donor interaction of the alpha-keto acid with the Fe. This promotes the transfer of charge from the Fe to NO. The calculations are extended to the O(2) reaction coordinate where the strong donation associated with the bound alpha keto acid promotes formation of a new, S = 1 bridged Fe(IV)-peroxy species. These studies provide insight into the effects of a strong donor ligand on O(2) binding and activation by Fe(II) in the alpha-keto acid-dependent dioxygenases and are likely relevant to other subgroups of the O(2) activating nonheme ferrous enzymes. PMID- 21981764 TI - Combined nitritation-anammox: advances in understanding process stability. AB - Efficient nitrogen removal from wastewater containing high concentrations of ammonium but little organic substrate has recently been demonstrated by several full-scale applications of the combined nitritation-anammox process. While the process efficiency is in most cases very good, process instabilities have been observed to result in temporary process failures. In the current study, conditions resulting in instability and strategies to regain efficient operation were evaluated. First, data from full-scale operation is presented, showing a sudden partial loss of activity followed by recovery within less than 1 month. Results from laboratory-scale experiments indicate that these dynamics observed in full scale can be caused by partial inhibition of the ammonia oxidizing bacteria (AOB), while anammox inhibition is a secondary effect due to temporarily reduced O(2) depletion. Complete anammox inhibition is observed at 0.2 mg O(2) . L(-1), resulting in NO(2)(-) accumulation. However, this inhibition of anammox is reversible within minutes after O(2) depletion. Thus, variable AOB activity was identified as the key to reactor stability. With appropriate interpretation of the online NH(4)(+) signal, accumulation of NO(2)(-) can be detected indirectly and used to signal an imbalance of O(2) supply and AOB activity (no suitable online NO(2)(-) electrode is currently available). Second, increased abundance of nitrite-oxidizing bacteria (NOB; competing with anammox for NO(2)(-)) is known as another cause of instability. Based on a comparison of parallel full-scale reactors, it is suggested that an infrequent and short-term increased O(2) supply (e.g., for maintenance of aerators) that exceeds prompt depletion of oxygen by AOB may have caused increased NOB abundance. The volumetric air supply as a proxy for O(2) supply thus needs to be linked to AOB activity. Further, NOB can be washed out of the system during regular operation if the system is operated at a sludge age in the range of 45 days and by controlling the air supply according to the NO(3)(-) concentration in the treated effluent. Early detection of growing NOB abundance while the population is still low can help guide process operation and it is suggested that molecular methods of quantifying NOB abundance should be tested. PMID- 21981765 TI - Comparisons of seven algorithms for pathway analysis using the WTCCC Crohn's Disease dataset. AB - BACKGROUND: Though rooted in genomic expression studies, pathway analysis for genome-wide association studies (GWAS) has gained increasing popularity, since it has the potential to discover hidden disease pathogenic mechanisms by combining statistical methods with biological knowledge. Generally, algorithms or programs proposed recently can be categorized by different types of input data, null hypothesis or counts of analysis stages. Due to complexity caused by SNP, gene and pathway relationships, re-sampling strategies like permutation are always utilized to derive an empirical distribution for test statistics for evaluating the significance of candidate pathways. However, evaluation of these algorithms on real GWAS datasets and real biological pathway databases needs to be addressed before we apply them widely with confidence. FINDINGS: Two algorithms which use summary statistics from GWAS as input were implemented in KGG, a novel and user friendly software tool for GWAS pathway analysis. Comparisons of these two algorithms as well as the other five selected algorithms were conducted by analyzing the WTCCC Crohn's Disease dataset utilizing the MsigDB canonical pathways. As a result of using permutation to obtain empirical p-value, most of these methods could control Type I error rate well, although some are conservative. However, the methods varied greatly in terms of power and running time, with the PLINK truncated set-based test being the most powerful and KGG being the fastest. CONCLUSIONS: Raw data-based algorithms, such as those implemented in PLINK, are preferable for GWAS pathway analysis as long as computational capacity is available. It may be worthwhile to apply two or more pathway analysis algorithms on the same GWAS dataset, since the methods differ greatly in their outputs and might provide complementary findings for the studied complex disease. PMID- 21981766 TI - Environmental exposure to lead and mercury in Mexican children: a real health problem. AB - Exposure to lead (Pb) and mercury (Hg) remains a world public health problem, particularly for young children in developing countries. In Mexico, the main sources of exposure to Pb and Hg are wastes from human activities that increase the natural sources of these metals. Pb and Hg are highly toxic during development and maturation periods of the central nervous system (CNS); these effects are associated with the risk for neurodegenerative diseases. Mexico has numerous exposure sources to Pb and Hg; nevertheless, information on exposure in children is limited, particularly for Hg. Therefore, we conducted a review of the studies performed in children exposed to Pb and Hg. Data presented support that an important proportion of Mexican children have Pb levels above values associated with dangerous effects. On the other hand, studies on Hg-exposure are scarce, so we need more studies to estimate the magnitude of the problem and to determine exposure levels in Mexican children. Available data support the urgent need for coordinated actions among researchers, and health and environmental government authorities to implement education and nutritional campaigns, as well as to decrease exposure and effects of Pb and Hg. In addition, there must be a priority for the implementation of educational campaigns directed to the general population, but with emphasis in parents, education staff and health care providers to decrease both the risk of exposure of children to Pb and Hg and the effects of the exposure to these metals. PMID- 21981767 TI - Understanding chronic non-communicable diseases in Latin America: towards an equity-based research agenda. AB - Although chronic non-communicable diseases are traditionally depicted as diseases of affluence, growing evidence suggests they strike along the fault lines of social inequality. The challenge of understanding how these conditions shape patterns of population health in Latin America requires an inter disciplinary lens. This paper reviews the burden of chronic non-communicable diseases in the region and examines key myths surrounding their prevalence and distribution. It argues that a social justice approach rooted in the idea of health inequity needs to be at the core of research in this area, and concludes with discussion of a new approach to guide empirical research, the 'average/deprivation/inequality' framework. PMID- 21981768 TI - Factors associated with work status at 5 and 10 years after heart transplantation. AB - AIM: Little is known regarding work status long-term after heart transplantation (HT). The purpose of this study was to examine demographic and clinical characteristics of patients who were working and not working, and to identify factors associated with working patients at five and 10 yr post-HT. METHODS: Data from patients (78% male, 88% white, mean age = 53.8 yr) at four US sites using the following instruments: Post-op Work History, Sickness Impact Profile (SIP), Quality of Life Index, Cardiac Depression Scale, and chart review were used. Statistical analyses included t-tests and logistic regression. RESULTS: The percentage of working patients at five yr remained steady over time to 10 yr post HT. Using the SIP, working patients had less overall, physical, and psychosocial functional disability at five yr. Working patients at five and 10 yr had significantly less depression than non-workers. Working patients at five yr had fewer co-existing illnesses than non-workers. Predictors of working at five and 10 yr included demographic, psychosocial, and clinical variables. CONCLUSION: Understanding rates of return to work and factors associated with return to work may assist clinicians as they discuss working after transplant with patients during evaluation for transplant and develop interventions to assist post transplant patients who want to return to work. PMID- 21981769 TI - Isolation and characterization of the unicellular diazotrophic cyanobacterium Group C TW3 from the tropical western Pacific Ocean. AB - A unicellular diazotrophic cyanobacterium strain of Group C, designated TW3, was isolated from the oligotrophic Kuroshio Current of the western Pacific Ocean. To our knowledge, this represents the first successful laboratory culture of a Group C unicellular diazotroph from oceanic water. TW3 cells are green rods, 2.5-3.0 um in width and 4.0-6.0 um in length. Phylogenetic analyses of both 16S rRNA and nifH gene fragments indicated that the TW3 sequences were over 98% identical to those of the previously isolated Cyanothece sp. ATCC51142 and Gloeocapsa sp., suggesting that TW3 is a member of the Group C unicellular diazotrophs. In addition, both TW3 and Cyanothece sp. ATCC51142 share morphological characteristics; both strains are sheathless and rod-shaped, display binary fission in a single plane, and possess dispersed thylakoids. TW3 grows aerobically in nitrogen-deficient artificial seawater, and exhibited the highest observed growth rate of 0.035 h(-1) when cultured at 30 degrees C and 140 umol m( 2) s(-1) of light intensity. The nitrogen fixation rate, when grown optimally using a 12 h/12 h light-dark cycle, was 7.31 * 10(-15) mol N cell(-1) day(-1) . Immunocytochemical staining using Trichodesmium sp. NIBB1067 nitrogenase antiserum revealed the existence of diazotrophic cells sharing morphological characteristics of TW3 in the Kuroshio water from which TW3 was isolated. PMID- 21981770 TI - Histopathologic characterization of mild rejection (grade I) in skin biopsies of human hand allografts. AB - Mild skin rejection is a common observation in reconstructive transplantation. To enlighten the role of this inflammatory reaction we investigated markers for cellular and antibody mediated rejection, adhesion molecules and tolerance markers. Forty-seven skin biopsies (rejection grade I) of human hand allografts were investigated by immunohistochemistry (CD3, CD4, CD8, CD20, CD68, C4d, LFA-1, ICAM-1, E-selectin, P-selectin, VE-cadherin, HLA-DR, IDO, and Foxp3). Expression was read with respect to time after transplant. The infiltrate was mainly comprised of CD3+T-lymphocytes. Among these, CD8+cells were more prominent than CD4+cells. CD20+B-lymphocytes were sparse and CD68+macrophages were found in some, but not all samples (approximately 10% of the infiltrate). The CD4/CD8 ratio was increased after the first year. C4d staining was mainly positive in samples at time-points later than 1 year. Adhesion molecules LFA-1, ICAM-1, E selectin, P-selectin, and VE-cadherin were found upregulated, and for P-selectin, expression increased with time after transplant. IDO expression was strongest at 3 months-1 year post-transplant and a tendency toward more Foxp3+ cells at later time points was observed. Mild skin rejection after hand transplantation presents with a T-cell dominated dermal cell infiltrate and upregulation of adhesion molecules. The role of C4d expression after year one remains to be elucidated. PMID- 21981771 TI - A mechanistic study of tumor-targeted corrole toxicity. AB - HerGa is a self-assembled tumor-targeted particle that bears both tumor detection and elimination activities in a single, two-component complex (Agadjanian et al. Proc. Natl. Acad. Sci. U.S.A.2009, 106, 6105-6110). Given its multifunctionality, HerGa (composed of the fluorescent cytotoxic corrole macrocycle, S2Ga, noncovalently bound to the tumor-targeted cell penetration protein, HerPBK10) has the potential for high clinical impact, but its mechanism of cell killing remains to be elucidated, and hence is the focus of the present study. Here we show that HerGa requires HerPBK10-mediated cell entry to induce toxicity. HerGa (but not HerPBK10 or S2Ga alone) induced mitochondrial membrane potential disruption and superoxide elevation, which were both prevented by endosomolytic-deficient mutants, indicating that cytosolic exposure is necessary for corrole-mediated cell death. A novel property discovered here is that corrole fluorescence lifetime acts as a pH indicator, broadcasting the intracellular microenvironmental pH during uptake in live cells. This feature in combination with two-photon imaging shows that HerGa undergoes early endosome escape during uptake, avoiding compartments of pH < 6.5. Cytoskeletal disruption accompanied HerGa-mediated mitochondrial changes whereas oxygen scavenging reduced both events. Paclitaxel treatment indicated that HerGa uptake requires dynamic microtubules. Unexpectedly, low pH is insufficient to induce release of the corrole from HerPBK10. Altogether, these studies identify a mechanistic pathway in which early endosomal escape enables HerGa-induced superoxide generation leading to cytoskeletal and mitochondrial damage, thus triggering downstream cell death. PMID- 21981772 TI - Body piercing and tattoos: a survey on young adults' knowledge of the risks and practices in body art. AB - BACKGROUND: The practice of tattooing and piercing has expanded in western society. In order to verify young adults' knowledge of the risk and practices related to body art, an investigation was conducted among freshmen of the University of Bari in the region of Apulia, Italy. METHODS: The study was carried out in the Academic Year 2009-2010 through an anonymous self-administered written questionnaire distributed to 1.656 freshmen enrolled in 17 Degree Courses. RESULTS: Of the 1.598 students included in the analysis, 78.3% believe it is risky to undergo piercing/tattoo practices. AIDS was indicated as a possible infection by 60.3% of freshmen, hepatitis C by 38.2%, tetanus by 34.3% and hepatitis B by 33.7% of the sample. 28.1% of freshmen were not aware that there are also non-infectious complications. 29% of the sample had at least one piercing or tattoo (this percentage does not include earlobe piercing in women). Of those with body art, the decision to undergo body art was made autonomously in 57.9% of the participants. 56.3% of freshmen undergoing body art had taken less than a month to decide. With regard to the reasons that led the sample to undergo body art, 28.4% were unable to explain it, 23.8% answered to improve their aesthetic aspect, 18.4% to distinguish themselves from others, 12.3% for fashion; 17.1% for other reasons. 25.4% of the sample declared that they had a piercing (79.8% female vs 20.2% male; ratio M/F 1:4.0). The average age for a first piercing was 15.3 years (range 10-27; SD +/- 2.9). 9.6% of the sample declared that they have a tattoo (69.9% female vs 30.1% male; ratio M/F 1:2.3). The average age for a first tattoo was 17.5 years (range 10-26, SD +/- 2.4). CONCLUSIONS: Most of the freshmen knew about AIDS-related risks but not other potential risks. Body art is fairly common among young adults (especially women). The decision is often not shared with the family and is undertaken mostly without a specific reason or for the improvement of aesthetic aspect. Information about freshmen's knowledge, attitudes and practices could help in effective planning of health promotion strategies. PMID- 21981773 TI - Physical properties of naked DNA influence nucleosome positioning and correlate with transcription start and termination sites in yeast. AB - BACKGROUND: In eukaryotic organisms, DNA is packaged into chromatin structure, where most of DNA is wrapped into nucleosomes. DNA compaction and nucleosome positioning have clear functional implications, since they modulate the accessibility of genomic regions to regulatory proteins. Despite the intensive research effort focused in this area, the rules defining nucleosome positioning and the location of DNA regulatory regions still remain elusive. RESULTS: Naked (histone-free) and nucleosomal DNA from yeast were digested by microccocal nuclease (MNase) and sequenced genome-wide. MNase cutting preferences were determined for both naked and nucleosomal DNAs. Integration of their sequencing profiles with DNA conformational descriptors derived from atomistic molecular dynamic simulations enabled us to extract the physical properties of DNA on a genomic scale and to correlate them with chromatin structure and gene regulation. The local structure of DNA around regulatory regions was found to be unusually flexible and to display a unique pattern of nucleosome positioning. Ab initio physical descriptors derived from molecular dynamics were used to develop a computational method that accurately predicts nucleosome enriched and depleted regions. CONCLUSIONS: Our experimental and computational analyses jointly demonstrate a clear correlation between sequence-dependent physical properties of naked DNA and regulatory signals in the chromatin structure. These results demonstrate that nucleosome positioning around TSS (Transcription Start Site) and TTS (Transcription Termination Site) (at least in yeast) is strongly dependent on DNA physical properties, which can define a basal regulatory mechanism of gene expression. PMID- 21981774 TI - ECT revisited: impact on major depression in borderline personality disorder. PMID- 21981775 TI - Manic induction with interferon alpha therapy. PMID- 21981776 TI - Association of chemerin mRNA expression in human epicardial adipose tissue with coronary atherosclerosis. AB - BACKGROUND: Growing evidence suggests that epicardial adipose tissue (EAT) may play a key role in the pathogenesis and development of coronary artery disease (CAD) by producing several inflammatory adipokines. Chemerin, a novel adipokine, has been reported to be involved in regulating immune responses and glucolipid metabolism. Given these properties, chemerin may provide an interesting link between obesity, inflammation and atherosclerosis. In this study, we sought to determine the relationship of chemerin expression in EAT and the severity of coronary atherosclerosis in Han Chinese patients. METHODS: Serums and adipose tissue biopsies (epicardial and thoracic subcutaneous) were obtained from CAD (n = 37) and NCAD (n = 16) patients undergoing elective cardiac surgery. Gensini score was used to assess the severity of CAD. Serum levels of chemerin, adiponectin and insulin were measured by ELISA. Chemerin protein expression in adipose tissue was detected by immunohistochemistry. The mRNA levels of chemerin, chemR23, adiponectin and TNF-alpha in adipose tissue were detected by RT-PCR. RESULTS: We found that EAT of CAD group showed significantly higher levels of chemerin and TNF-alpha mRNA, and significantly lower level of adiponectin mRNA than that of NCAD patients. In CAD group, significantly higher levels of chemerin mRNA and protein were observed in EAT than in paired subcutaneous adipose tissue (SAT), whereas such significant difference was not found in NCAD group. Chemerin mRNA expression in EAT was positively correlated with Gensini score (r = 0.365, P < 0.05), moreover, this correlation remained statistically significant (r = 0.357, P < 0.05) after adjusting for age, gender, BMI and waist circumference. Chemerin mRNA expression in EAT was also positively correlated with BMI (r = 0.305, P < 0.05), waist circumference (r = 0.384, P < 0.01), fasting blood glucose (r = 0.334, P < 0.05) and negatively correlated with adiponectin mRNA expression in EAT (r = -0.322, P < 0.05). However, there were no significant differences in the serum levels of chemerin or adiponectin between the two groups. Likewise, neither serum chemerin nor serum adiponectin was associated with Gensini score (P > 0.05). CONCLUSIONS: The expressions of chemerin mRNA and protein are significantly higher in EAT from patients with CAD in Han Chinese patients. Furthermore, the severity of coronary atherosclerosis is positive correlated with the level of chemerin mRNA in EAT rather than its circulating level. PMID- 21981777 TI - An automated platform for phytoplankton ecology and aquatic ecosystem monitoring. AB - High quality monitoring data are vital for tracking and understanding the causes of ecosystem change. We present a potentially powerful approach for phytoplankton and aquatic ecosystem monitoring, based on integration of scanning flow-cytometry for the characterization and counting of algal cells with multiparametric vertical water profiling. This approach affords high-frequency data on phytoplankton abundance, functional traits and diversity, coupled with the characterization of environmental conditions for growth over the vertical structure of a deep water body. Data from a pilot study revealed effects of an environmental disturbance event on the phytoplankton community in Lake Lugano (Switzerland), characterized by a reduction in cytometry-based functional diversity and by a period of cyanobacterial dominance. These changes were missed by traditional limnological methods, employed in parallel to high-frequency monitoring. Modeling of phytoplankton functional diversity revealed the importance of integrated spatiotemporal data, including circadian time-lags and variability over the water column, to understand the drivers of diversity and dynamic processes. The approach described represents progress toward an automated and trait-based analysis of phytoplankton natural communities. Streamlining of high-frequency measurements may represent a resource for understanding, modeling and managing aquatic ecosystems under impact of environmental change, yielding insight into processes governing phytoplankton community resistance and resilience. PMID- 21981778 TI - Exploring the interaction between siRNA and the SMoC biomolecule transporters: implications for small molecule-mediated delivery of siRNA. AB - The small molecule carrier class of biomolecule transporters, modeled on the third helix of the Antennapedia homeodomain, has previously been shown to transport active proteins into cells. Here, we show an improved synthetic route to small molecule carriers, including Molander chemistry using trifluoroborate salts to improve the yield of the Suzuki-Miyaura coupling step for the formation of the biphenyl backbone. The required boronic acids could be formed by the reaction of a 2-(dimethylamino)ethyl ether-modified aryl Grignard reagent with triisopropyl borate. The potential for the use of small molecule carriers as oligonucleotide-transporting agents was also explored by characterizing the interactions between small molecule carriers and siRNA. Molecular dynamics and NMR analysis indicated that the small molecule carrier guanidines are stabilized by pi-cation interactions with the biphenyl system, thus not only increasing the basicity or pKa but also shielding the charge. The binding affinities of various small molecule carriers for siRNA were investigated using isothermal calorimetry and gel shift assays. Small molecule carrier-mediated siRNA delivery to cultured fibroblasts is demonstrated, showing that small molecule carriers possess the ability to transport functional siRNA into cells. Knockdown of Cdc7 kinase, a target for cancer, is achieved. PMID- 21981779 TI - Variants near FOXE1 are associated with hypothyroidism and other thyroid conditions: using electronic medical records for genome- and phenome-wide studies. AB - We repurposed existing genotypes in DNA biobanks across the Electronic Medical Records and Genomics network to perform a genome-wide association study for primary hypothyroidism, the most common thyroid disease. Electronic selection algorithms incorporating billing codes, laboratory values, text queries, and medication records identified 1317 cases and 5053 controls of European ancestry within five electronic medical records (EMRs); the algorithms' positive predictive values were 92.4% and 98.5% for cases and controls, respectively. Four single-nucleotide polymorphisms (SNPs) in linkage disequilibrium at 9q22 near FOXE1 were associated with hypothyroidism at genome-wide significance, the strongest being rs7850258 (odds ratio [OR] 0.74, p = 3.96 * 10(-9)). This association was replicated in a set of 263 cases and 1616 controls (OR = 0.60, p = 5.7 * 10(-6)). A phenome-wide association study (PheWAS) that was performed on this locus with 13,617 individuals and more than 200,000 patient-years of billing data identified associations with additional phenotypes: thyroiditis (OR = 0.58, p = 1.4 * 10(-5)), nodular (OR = 0.76, p = 3.1 * 10(-5)) and multinodular (OR = 0.69, p = 3.9 * 10(-5)) goiters, and thyrotoxicosis (OR = 0.76, p = 1.5 * 10( 3)), but not Graves disease (OR = 1.03, p = 0.82). Thyroid cancer, previously associated with this locus, was not significantly associated in the PheWAS (OR = 1.29, p = 0.09). The strongest association in the PheWAS was hypothyroidism (OR = 0.76, p = 2.7 * 10(-13)), which had an odds ratio that was nearly identical to that of the curated case-control population in the primary analysis, providing further validation of the PheWAS method. Our findings indicate that EMR-linked genomic data could allow discovery of genes associated with many diseases without additional genotyping cost. PMID- 21981780 TI - Absence of an orphan mitochondrial protein, c19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation. AB - The disease classification neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of progressive neurodegenerative disorders characterized by brain iron deposits in the basal ganglia. For about half of the cases, the molecular basis is currently unknown. We used homozygosity mapping followed by candidate gene sequencing to identify a homozygous 11 bp deletion in the orphan gene C19orf12. Mutation screening of 23 ideopathic NBIA index cases revealed two mutated alleles in 18 of them, and one loss-of-function mutation is the most prevalent. We also identified compound heterozygous missense mutations in a case initially diagnosed with Parkinson disease at age 49. Psychiatric signs, optic atrophy, and motor axonal neuropathy were common findings. Compared to the most prevalent NBIA subtype, pantothenate kinase associated neurodegeneration (PKAN), individuals with two C19orf12 mutations were older at age of onset and the disease progressed more slowly. A polyclonal antibody against the predicted membrane spanning protein showed a mitochondrial localization. A histopathological examination in a single autopsy case detected Lewy bodies, tangles, spheroids, and tau pathology. The mitochondrial localization together with the immunohistopathological findings suggests a pathomechanistic overlap with common forms of neurodegenerative disorders. PMID- 21981784 TI - Optimising MUCT imaging of the middle and inner cat ear. AB - This study's aim was to determine the optimal scan parameters for imaging the middle and inner ear of the cat with micro-computertomography (MUCT). Besides, the study set out to assess whether adequate image quality can be obtained to use MUCT in diagnostics and research on cat ears. For optimisation, MUCT imaging of two cat skull preparations was performed using 36 different scanning protocols. The MUCT-scans were evaluated by four experienced experts with regard to the image quality and detail detectability. By compiling a ranking of the results, the best possible scan parameters could be determined. From a third cat's skull, a MUCT-scan, using these optimised scan parameters, and a comparative clinical CT scan were acquired. Afterwards, histological specimens of the ears were produced which were compared to the MUCT-images. The comparison shows that the osseous structures are depicted in detail. Although soft tissues cannot be differentiated, the osseous structures serve as valuable spatial orientation of relevant nerves and muscles. Clinical CT can depict many anatomical structures which can also be seen on MUCT-images, but these appear a lot less sharp and also less detailed than with MUCT. PMID- 21981781 TI - Assessment of 2q23.1 microdeletion syndrome implicates MBD5 as a single causal locus of intellectual disability, epilepsy, and autism spectrum disorder. AB - Persons with neurodevelopmental disorders or autism spectrum disorder (ASD) often harbor chromosomal microdeletions, yet the individual genetic contributors within these regions have not been systematically evaluated. We established a consortium of clinical diagnostic and research laboratories to accumulate a large cohort with genetic alterations of chromosomal region 2q23.1 and acquired 65 subjects with microdeletion or translocation. We sequenced translocation breakpoints; aligned microdeletions to determine the critical region; assessed effects on mRNA expression; and examined medical records, photos, and clinical evaluations. We identified a single gene, methyl-CpG-binding domain 5 (MBD5), as the only locus that defined the critical region. Partial or complete deletion of MBD5 was associated with haploinsufficiency of mRNA expression, intellectual disability, epilepsy, and autistic features. Fourteen alterations, including partial deletions of noncoding regions not typically captured or considered pathogenic by current diagnostic screening, disrupted MBD5 alone. Expression profiles and clinical characteristics were largely indistinguishable between MBD5-specific alteration and deletion of the entire 2q23.1 interval. No copy-number alterations of MBD5 were observed in 7878 controls, suggesting MBD5 alterations are highly penetrant. We surveyed MBD5 coding variations among 747 ASD subjects compared to 2043 non-ASD subjects analyzed by whole-exome sequencing and detected an association with a highly conserved methyl-CpG-binding domain missense variant, p.79Gly>Glu (c.236G>A) (p = 0.012). These results suggest that genetic alterations of MBD5 cause features of 2q23.1 microdeletion syndrome and that this epigenetic regulator significantly contributes to ASD risk, warranting further consideration in research and clinical diagnostic screening and highlighting the importance of chromatin remodeling in the etiology of these complex disorders. PMID- 21981782 TI - Frequency of nonallelic homologous recombination is correlated with length of homology: evidence that ectopic synapsis precedes ectopic crossing-over. AB - Genomic disorders constitute a class of diseases that are associated with DNA rearrangements resulting from region-specific genome instability, that is, genome architecture incites genome instability. Nonallelic homologous recombination (NAHR) or crossing-over in meiosis between sequences that are not in allelic positions (i.e., paralogous sequences) can result in recurrent deletions or duplications causing genomic disorders. Previous studies of NAHR have focused on description of the phenomenon, but it remains unclear how NAHR occurs during meiosis and what factors determine its frequency. Here we assembled two patient cohorts with reciprocal genomic disorders; deletion associated Smith-Magenis syndrome and duplication associated Potocki-Lupski syndrome. By assessing the full spectrum of rearrangement types from the two cohorts, we find that complex rearrangements (those with more than one breakpoint) are more prevalent in copy number gains (17.7%) than in copy-number losses (2.3%); an observation that supports a role for replicative mechanisms in complex rearrangement formation. Interestingly, for NAHR-mediated recurrent rearrangements, we show that crossover frequency is positively associated with the flanking low-copy repeat (LCR) length and inversely influenced by the inter-LCR distance. To explain this, we propose that the probability of ectopic chromosome synapsis increases with increased LCR length, and that ectopic synapsis is a necessary precursor to ectopic crossing over. PMID- 21981785 TI - Implementation and external validation of preoperative aspects and dimensions used for an anatomical (padua) score for predicting complications in 74 consecutive partial nephrectomies. PMID- 21981786 TI - The genetic validation of heterogeneity in schizophrenia. AB - INTRODUCTION: Schizophrenia is a heritable disorder, however clear genetic architecture has not been detected. To overcome this state of uncertainty, the SZGene database has been established by including all published case-control genetic association studies appearing in peer-reviewed journals. In the current study, we aimed to determine if genetic variants strongly suggested by SZGene are associated with risk of schizophrenia in our case-control samples of Japanese ancestry. In addition, by employing the additive model for aggregating the effect of seven variants, we aimed to verify the genetic heterogeneity of schizophrenia diagnosed by an operative diagnostic manual, the DSM-IV. METHODS: Each positively suggested genetic polymorphism was ranked according to its p-value, then the seven top-ranked variants (p < 0.0005) were selected from DRD2, DRD4, GRIN2B, TPH1, MTHFR, and DTNBP1 (February, 2007). 407 Schizophrenia cases and 384 controls participated in this study. To aggregate the vulnerability of the disorder based on the participants' genetic information, we calculated the "risk index" by adding the number of genetic risk factors. RESULTS: No statistically significant deviation between cases and controls was observed in the genetic risk index derived from all seven variants on the top-ranked polymorphisms. In fact, the average risk-index score in the schizophrenia group (6.5+/-1.57) was slightly lower than among controls (6.6+/-1.39). CONCLUSION: The current work illustrates the difficulty in identifying universal and definitive risk-conferring polymorphisms for schizophrenia. Our employed number of samples was small, so we can not preclude the possibility that some or all of these variants are minor risk factors for schizophrenia in the Japanese population. It is also important to aggregate the updated positive variants in the SZGene database when the replication work is conducted. PMID- 21981787 TI - The impact of liver disease aetiology and the stages of hepatic fibrosis on the performance of non-invasive fibrosis biomarkers: an international study of 2411 cases. AB - BACKGROUND: Performance of non-invasive fibrosis biomarkers may be influenced by aetiology of chronic liver disease (CLD) and the stages of hepatic fibrosis, but large-scale studies are pending. AIM: To investigate the effect of aetiogy and stages of hepatic fibrosis on the performance of fibrosis biomarkers. METHODS: A total of 2411 patients with compensated CLD (HCV=75.1%, HBV=10.5%, NASH=7.9%, HIV/HCV=6.5%) were consecutively enrolled in 9 centres. APRI, Forns'index, Lok index, AST-to-ALT ratio, Fib-4, platelets and Fibrotest-Fibrosure were tested against liver biopsy, considered the gold standard. The effect of the stages of hepatic fibrosis to diagnose significant fibrosis and cirrhosis (>=F2 and F4 respectively) was investigated through difference between advanced and non advanced fibrosis stages (DANA). Performance was expressed as observed area under the ROC curve (ObAUROC) and AUROC adjusted for DANA (AdjAUROC). RESULTS: Performance of APRI and Fibrotest-Fibrosure was higher than other biomarkers. In all aetiologies, AdjAUROC was higher than ObAUROC. APRI showed its best performance in HCV monoinfected cases, with an AdjAUROC of 0.77 and 0.83 for >=F2 and F4 respectively. In HBV and non-alcoholic steatohepatitis (NASH) patients, its performance was poor (AdjAUROC <0.70). Performance of Fibrotest-Fibrosure was good in all aetiologies for both >=F2 and F4 (AdjAUROC >0.73), except for >=F2 in NASH (AdjAUROC = 0.64). Performance of all biomarkers was reduced in HCV cases with normal ALT. CONCLUSIONS: Aetiology is a major factor influencing the performance of liver fibrosis biomarkers. Even after correction for DANA, APRI and Fibrotest-Fibrosure exhibit the best performance. However, liver biopsy is not replaceable, especially to diagnose >=F2 and in HCV carriers with normal ALT. PMID- 21981789 TI - Performance evaluation of 26 combinations of chemical protective clothing materials and chemicals after repeated exposures and decontaminations. AB - Effective decontamination of chemical protective clothing (CPC) is essential for reducing occupational skin diseases and disorders during a reuse scenario. To protect the workforce, the efficacy of decontamination methods and the reusability of CPC need to be evaluated. In this study, performance of 14 CPC materials against 12 liquid chemicals was evaluated based on standardized breakthrough time (BT) and steady-state permeation rate (SSPR). Thermal and water detergent decontamination methods were used. Exposure/decontamination was repeated up to 11 cycles, or until the material failed, so that further testing became impossible. Changes in BT and SSPRs were determined for each material and chemical combination. There were 20 and 13 combinations that were able to complete 11 cycles with thermal and detergent methods, respectively. By comparing the beginning and ending cycles, mean BT increased 9% with the thermal method but slightly decreased (3.3%) with the detergent method, while mean SSPR decreased 2% with the thermal method, but slightly increased (1.4%) with the detergent method. Less than half of the changes were found statistically different (p < 0.05). Generally, the thermal method had higher decontamination efficacy than the detergent method. PMID- 21981790 TI - Measuring health-related quality of life in men with osteoporosis or osteoporotic fracture. AB - BACKGROUND: Osteoporosis is a serious health problem that worsens the quality of life and the survival rate of individuals with this disease on account the osteoporotic fractures. Studies have long focused on women, and its presence in men has been underestimated. While many studies conducted in different countries mainly assess health-related quality of life and identify fracture risks factors in women, few data are available on a Spanish male population. METHODS/DESIGN: Observational study. STUDY POPULATION: Men >= 40 years of age with/without diagnosed osteoporosis and with/without osteoporotic fracture included by their family doctor. MEASUREMENTS: The relationship between customary clinical risk factors for osteoporotic fracture and health-related quality of life in a Spanish male population. A telephone questionnaire on health-related quality of life is made. STATISTICAL ANALYSIS: The association between qualitative variables will be assessed by the Chi-square test. The distribution of quantitative variables by Student's t-test. If the conditions for using this test are not met, the non parametric Mann-Whitney's U test will be used.The validation of the results obtained by the FRAXTM tool will be performed by way of the Hosmer-Lemeshow test and by calculating the area under the Receiver Operating Characteristic (ROC) curve (AUC). All tests will be performed with a confidence intervals set at 95%. DISCUSSION: The applicability and usefulness of Health-related quality of life (HRQOL) studies are well documented in many countries. These studies allow implementing cost-effective measures in cases of a given disease and reducing the costly consequences derived therefrom. This study attempts to provide objective data on how quality of life is affected by the clinical aspects involved in osteoporosis in a Spanish male population and can be useful as well in cost utility analyses conducted by health authorities.The sample selected is not based on a high fracture risk group. Rather, it is composed of men in the general population, and accordingly comparisons should not lead to erroneous interpretations.A possible bias correction will be ensured by checking reported fractures against healthcare reports and X-rays, or by consulting health care centers as applicable. PMID- 21981791 TI - Awareness and acceptance of public cord blood banking among practicing obstetricians in the United States. AB - BACKGROUND: This study measured: 1) levels of awareness and understanding among practicing obstetricians regarding umbilical cord blood (UCB) donation and the use of UCB in transplant therapy, 2) motivations for obstetricians to support donation and collection for donation to a public cord blood bank (CBB), and 3) current practices for discussing this option with their patients. STUDY DESIGN AND METHODS: Obstetricians practicing in major metropolitan areas in the United States were randomly surveyed in 2009. Of 2041 surveys mailed, 295 were returned, 139 from obstetricians with privileges at hospitals affiliated with a public CBB (affiliated) and 156 from obstetricians without such privileges (nonaffiliated). Cross-tabulation analyses were conducted to compare responses between these two groups. RESULTS: Both affiliated and nonaffiliated obstetricians report being somewhat or very familiar with the use of cord blood in transplant therapy (88% vs. 82%, respectively; p = NS), but some misperceptions concerning clinical application exist. Eighty percent of affiliated obstetricians feel confident discussing cord blood options with their patients; however, 49% indicated that they have insufficient knowledge of cord blood donation to effectively answer patients' questions about donation. CONCLUSION: Obstetricians are generally familiar with the utility of donated cord blood in transplantation, but could benefit from additional information regarding how cord blood is used in transplantation. Further, obstetricians play an important role in encouraging women to donate their baby's cord blood to a public CBB, are willing to do so, and indicate a desire for more information so they can effectively educate their patients. PMID- 21981788 TI - Treatment of substance abusing patients with comorbid psychiatric disorders. AB - OBJECTIVE: To update clinicians on the latest in evidence-based treatments for substance use disorders (SUD) and non-substance use disorders among adults and suggest how these treatments can be combined into an evidence-based process that enhances treatment effectiveness in comorbid patients. METHOD: Articles were extracted from Pubmed using the search terms "dual diagnosis," "comorbidity" and "co-occurring" and were reviewed for evidence of effectiveness for pharmacologic and psychotherapeutic treatments of comorbidity. RESULTS: Twenty-four research reviews and 43 research trials were reviewed. The preponderance of the evidence suggests that antidepressants prescribed to improve substance-related symptoms among patients with mood and anxiety disorders are either not highly effective or involve risk due to high side-effect profiles or toxicity. Second generation antipsychotics are more effective for treatment of schizophrenia and comorbid substance abuse and current evidence suggests clozapine, olanzapine and risperidone are among the best. Clozapine appears to be the most effective of the antipsychotics for reducing alcohol, cocaine and cannabis abuse among patients with schizophrenia. Motivational interviewing has robust support as a highly effective psychotherapy for establishing a therapeutic alliance. This finding is critical since retention in treatment is essential for maintaining effectiveness. Highly structured therapy programs that integrate intensive outpatient treatments, case management services and behavioral therapies such as Contingency Management (CM) are most effective for treatment of severe comorbid conditions. CONCLUSIONS: Creative combinations of psychotherapies, behavioral and pharmacological interventions offer the most effective treatment for comorbidity. Intensity of treatment must be increased for severe comorbid conditions such as the schizophrenia/cannabis dependence comorbidity due to the limitations of pharmacological treatments. PMID- 21981792 TI - Patient environment microbial burden reduction: a pilot study comparison of 2 terminal cleaning methods. AB - Effective cleaning of the patient environment has been advocated to reduce the risk for nosocomial infection. This pilot study compared 2 terminal cleaning methods, a traditional method in which a disinfectant was applied with a wetted cloth and an alternative method in which the disinfectant was applied using the PureMist system (PureCart Systems, Green Bay, WI). There was no difference in effectiveness, with a mean relative reduction of microbial burden of 84% for the traditional method versus 88% for the PureMist method. PMID- 21981793 TI - Extent and patterns of community collaboration in local health departments: An exploratory survey. AB - BACKGROUND: Local public health departments (LHDs) in the United States have been encouraged to collaborate with various other community organizations and individuals. Current research suggests that many forms of active partnering are ongoing, and there are numerous examples of LHD collaboration with a specific organization for a specific purpose or program. However, no existing research has attempted to characterize collaboration, for the defined purpose of setting community health status priorities, between a defined population of local officials and a defined group of alternative partnering organizations. The specific aims of this study were to 1) determine the range of collaborative involvement exhibited by a study population of local public health officials, and, 2) characterize the patterns of the selection of organizations/individuals involved with LHDs in the process of setting community health status priorities. METHODS: Local health department officials in North Carolina (n = 53) responded to an exploratory survey about their levels of involvement with eight types of possible collaborator organizations and individuals. Descriptive statistics and the stochastic clustering technique of Self-Organizing Maps (SOM) were used to characterize their collaboration. RESULTS: Local health officials vary extensively in their level of collaboration with external collaborators. While the range of total involvement varies, the patterns of involvement for this specific function are relatively uniform. That is, regardless of the total level of involvement (low, medium or high), officials maintain similar hierarchical preference rankings with Community Advisory Boards and Local Boards of Health most involved and Experts and Elected Officials least involved. CONCLUSION: The extent and patterns of collaboration among LHDs with other community stakeholders for a specific function can be described and ultimately related to outcome measures of LHD performance. PMID- 21981795 TI - How today's robots work and perspectives for the future. PMID- 21981794 TI - Aging enhances the production of reactive oxygen species and bactericidal activity in peritoneal macrophages by upregulating classical activation pathways. AB - Maintenance of macrophages in their basal state and their rapid activation in response to pathogen detection are central to the innate immune system, acting to limit nonspecific oxidative damage and promote pathogen killing following infection. To identify possible age-related alterations in macrophage function, we have assayed the function of peritoneal macrophages from young (3-4 months) and aged (14-15 months) Balb/c mice. In agreement with prior suggestions, we observe age-dependent increases in the extent of recruitment of macrophages into the peritoneum, as well as ex vivo functional changes involving enhanced nitric oxide production under resting conditions that contribute to a reduction in the time needed for full activation of senescent macrophages following exposure to lipopolysaccharides (LPS). Further, we observe enhanced bactericidal activity following Salmonella uptake by macrophages isolated from aged Balb/c mice in comparison with those isolated from young animals. Pathways responsible for observed phenotypic changes were interrogated using tandem mass spectrometry, which identified age-dependent increases in levels of proteins linked to immune cell pathways under basal conditions and following LPS activation. Immune pathways upregulated in macrophages isolated from aged mice include proteins critical to the formation of the immunoproteasome. Detection of these latter proteins is dramatically enhanced following LPS exposure for macrophages isolated from aged animals; in comparison, the identification of immunoproteasome subunits is insensitive to LPS exposure for macrophages isolated from young animals. Consistent with observed global changes in the proteome, quantitative proteomic measurements indicate that there are age-dependent abundance changes involving specific proteins linked to immune cell function under basal conditions. LPS exposure selectively increases the levels of many proteins involved in immune cell function in aged Balb/c mice. Collectively, these results indicate that macrophages isolated from old mice are in a preactivated state that enhances their sensitivities to LPS exposure. The hyper-responsive activation of macrophages in aged animals may act to minimize infection by general bacterial threats that arise due to age-dependent declines in adaptive immunity. However, this hypersensitivity and the associated increase in the level of formation of reactive oxygen species are likely to contribute to observed age-dependent increases in the level of oxidative damage that underlie many diseases of the elderly. PMID- 21981796 TI - Many thanks to Francois Lacaine. PMID- 21981799 TI - Protocol implementation of selective postoperative lumbar spinal drainage after thoracic aortic endograft. AB - BACKGROUND: Spinal cord ischemia (SCI) remains a significant concern in patients undergoing endovascular repair involving the thoracic aorta (thoracic endovascular aortic repair [TEVAR]). Perioperative lumbar spinal drainage has been widely practiced for open repair, but there is no consensus treatment protocol using lumbar drainage for SCI associated with TEVAR. This study analyzes the efficacy of an institutional protocol using selective lumbar drainage reserved for patients experiencing SCI following TEVAR. METHODS: A prospectively maintained registry was reviewed to identify all patients who underwent TEVAR from January 2000 through June 2010. Preoperative characteristics, intraoperative details, and outcomes, including neurologic deficit and mortality at 30 days and 1 year were determined based on reporting standards. Patients developing symptoms of SCI in the postoperative setting were compared with those without neurologic symptoms. SCI patients who received selective lumbar drainage were grouped based on resolution of neurologic function, with risk factors and outcomes of these subgroups analyzed with chi(2), t test, logistic regression, and analysis of variance (ANOVA). RESULTS: Two hundred seventy-eight TEVARs were performed on 251 patients. Twelve patients accounting for 12 TEVARs were excluded from analysis: 5 patients experienced SCI preoperatively, 4 patients were drained preoperatively, 2 expired intraoperatively, and 1 procedure was aborted. Of the remaining 266 procedures in 239 patients, 16 (6.0%) developed SCI within the 30-day postoperative period. Risk factors for SCI reaching statistical significance included length of aortic coverage (P = .036), existence of infrarenal aortic pathology (P = .026), and history of stroke (P = .043). Stent graft coverage of the left subclavian artery origin was required in 28.9% (n = 77) and was not associated with SCI (P = .52). Ten of 16 post-TEVAR SCI patients received selective postoperative lumbar drains and were categorized based on resolution of symptoms into complete resolution (n = 3; 30%), partial resolution (n = 4; 40%), and no resolution (n = 3; 30%). No patient characteristics or risk factors reached significance in comparison of lumbar drained patients and nondrained patients. All seven drained patients without complete resolution of SCI died within the first year after surgery, while all three of the complete responders survived (P = .017). In patients with SCI, increased all-cause mortality was observed at 1 year (56.3% vs 20.4%; P = .003). CONCLUSIONS: A protocol utilizing selective postoperative lumbar spinal drainage can be used safely for patients developing SCI after TEVAR with acceptably low permanent neurologic deficit, although overall survival of patients experiencing SCI after TEVAR is diminished relative to non-SCI patients. PMID- 21981797 TI - Development and comparison of a warfarin-dosing algorithm for Korean patients with atrial fibrillation. AB - BACKGROUND: The pharmacokinetics and pharmacodynamics of warfarin are affected by polymorphisms in the genes coding for cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1). OBJECTIVE: The objective of this study was to develop a pharmacogenetic dosing algorithm for warfarin in Korean patients with atrial fibrillation and to compare it with the published pharmacogenetic dosing algorithms for accuracy to predict warfarin maintenance dose. METHODS: Clinical and genetic data from 130 Korean patients with atrial fibrillation (mean [SD] age: 66.2 [13.3] years; gender, male/female: 86/44; mean body weight: 66.6 [11.6] kg) were used to create a dosing algorithm, which was validated against an independent group of patients (n = 108; mean age: 67.4 [10.1] years; gender, male/female: 69/39; mean body weight: 66.0 [10.9] kg). Validation cohort data for the 12 previously published dosing algorithms incorporating CYP2C9 and VKORC1 genotype information were also applied. RESULTS: A multivariate regression model including the variables of age, VKORC1 and CYP2C9 genotype, body surface area, and statin status produced the best model for estimating the warfarin dose (R(2) = 0.62). Among the 12 algorithms that were compared, the predicted doses using algorithms derived from both the Swedish Warfarin Genetics (WARG) study and the Korean population study showed the best correlation with actual warfarin doses. Comparing the percentage of patients whose predicted dosages were within 20% of actual dosages, these algorithms showed similar overall performance. CONCLUSIONS: This study derived and validated a multivariate regression model for daily warfarin dose requirements in Korean patients with atrial fibrillation. As no algorithm could be considered the best for all dosing ranges, it may be important to consider the characteristics or limitations of each dosing algorithm and the nature of a population in choosing the most appropriate pharmacogenetic dosing. PMID- 21981801 TI - Effect of a centrally active angiotensin converting enzyme inhibitor, perindopril, on cognitive performance in chronic cerebral hypo-perfusion rats. AB - We have previously demonstrated that perindopril, an angiotensin-converting enzyme (ACE) inhibitor, ameliorated the cognitive deficits in Alzheimer's disease model animals, independently of its anti-hypertensive effect. In this study, we again investigated the effects of perindopril on cognitive function in a vascular dementia model animal, comparing it with other ACE inhibitors. We also determined ACE activity in the brain and extracellular acetylcholine (ACh) concentration in the perirhinal cortex in order to elucidate the mechanism(s) responsible for the effects of these ACE inhibitors on cognitive function. Perindopril was suggested to be more centrally active than imidapril and enalapril, in consideration of the relative distribution of their active metabolites in the brain. This property was at least partially attributed to the lipophilicity of the compound. While the 3 day treatment with perindopril, imidapril or enalapril lowered blood pressure to the same level in spontaneous hypertensive rats, only perindopril reversed the decline in the recognition index in chronic cerebral hypo-perfusion rats, regarded as an animal model of vascular dementia, during an object recognition task. Using the same dosing regimen, perindopril inhibited the brain ACE activities of rats more than imidapril or enalapril. Moreover, a single treatment with perindopril enhanced the extracellular level of ACh in the perirhinal cortex of normal rats. Therefore, we confirmed that only centrally active ACE inhibitors, such as perindopril, can inhibit the ACE in the brain, augmenting cholinergic neurotransmission and thereby ameliorating cognitive impairment in the animal model of vascular dementia. PMID- 21981800 TI - Skin healing and scale regeneration in fed and unfed sea bream, Sparus auratus. AB - BACKGROUND: Fish scales are an important reservoir of calcium and phosphorus and together with the skin function as an integrated barrier against environmental changes and external aggressors. Histological studies have revealed that the skin and scales regenerate rapidly in fish when they are lost or damaged. In the present manuscript the histological and molecular changes underlying skin and scale regeneration in fed and fasted sea bream (Sparus auratus) were studied using a microarray 3 and 7 days after scale removal to provide a comprehensive molecular understanding of the early stages of these processes. RESULTS: Histological analysis of skin/scales revealed 3 days after scale removal re epithelisation and formation of the scale pocket had occurred and 53 and 109 genes showed significant up or down-regulation, respectively. Genes significantly up-regulated were involved in cell cycle regulation, cell proliferation and adhesion, immune response and antioxidant activities. 7 days after scale removal a thin regenerated scale was visible and only minor changes in gene expression occurred. In animals that were fasted to deplete mineral availability the expression profiles centred on maintaining energy homeostasis. The utilisation of fasting as a treatment emphasised the competing whole animal physiological requirements with regard to barrier repair, infection control and energy homeostasis. CONCLUSIONS: The identification of numerous genes involved in the mitotic checkpoint and cell proliferation indicate that the experimental procedure may be useful for understanding cell proliferation and control in vertebrates within the context of the whole animal physiology. In response to skin damage genes of immune surveillance were up-regulated along with others involved in tissue regeneration required to rapidly re-establish barrier function. Additionally, candidate fish genes were identified that may be involved in cytoskeletal re-modelling, mineralization and stem cells, which are of potential use in aquaculture and fish husbandry, as they may impact on the ability of the fish to produce structural proteins, such as muscle, efficiently. PMID- 21981802 TI - Detecting dependencies between spike trains of pairs of neurons through copulas. AB - The dynamics of a neuron are influenced by the connections with the network where it lies. Recorded spike trains exhibit patterns due to the interactions between neurons. However, the structure of the network is not known. A challenging task is to investigate it from the analysis of simultaneously recorded spike trains. We develop a non-parametric method based on copulas, that we apply to simulated data according to different bivariate Leaky Integrate and Fire models. The method discerns dependencies determined by the surrounding network, from those determined by direct interactions between the two neurons. Furthermore, the method recognizes the presence of delays in the spike propagation. This article is part of a Special Issue entitled "Neural Coding". PMID- 21981803 TI - Mechanisms underlying flexible adaptation of cognitive control: behavioral and neuroimaging evidence in a flanker task. AB - Cognitive control can be adapted flexibly according to the conflict level in a given situation. In the Eriksen flanker task, interference evoked by flankers is larger in conditions with a higher, rather than a lower proportion of compatible trials. Such compatibility ratio effects also occur for stimuli presented at two spatial locations suggesting that different cognitive control settings can be simultaneously maintained. However, the conditions and the neural correlates of this flexible adaptation of cognitive control are only poorly understood. In the present study, we further elucidated the mechanisms underlying the simultaneous maintenance of two cognitive control settings. In behavioral experiments, stimuli were presented centrally above and below fixation and hence processed by both hemispheres or lateralized to stimulate hemispheres differentially. The different compatibility ratio at two stimulus locations had a differential influence on the flanker effect in both experiments. In an fMRI experiment, blocks with an identical compatibility ratio at two central spatial locations elicited stronger activity in a network of prefrontal and parietal brain areas, which are known to be involved in conflict resolution and cognitive control, as compared with blocks with a different compatibility ratio at the same spatial locations. This demonstrates that the simultaneous maintenance of two conflicting control settings vs. one single setting does not recruit additional neural circuits suggesting the involvement of one single cognitive control system. Instead a crosstalk between multiple control settings renders adaptation of cognitive control more efficient when only one uniform rather than two different control settings has to be simultaneously maintained. PMID- 21981804 TI - Superoxide anion contributes to the induction of tumor necrosis factor alpha (TNFalpha) through activation of the MKK3/6-p38 MAPK cascade in rat microglia. AB - Stimulation of rat microglia with lipopolysaccharide (LPS) in vitro induces production of the inflammatory/cytotoxic cytokine tumor necrosis factor alpha (TNFalpha) along with superoxide anion (O(2)(-)) and nitric oxide (NO). In this study, we investigated the role of O(2)(-) and NO in the induction of TNFalpha in microglia. The LPS-inducible TNFalpha was significantly suppressed by pretreatment with the O(2)(-) scavenger N-acetyl cysteine (NAC), but not by the NO scavenger 2-(4-Carboxyphenyl)-4,4,5,5-tetramethyl imidazoline-1-oxyl 3-oxide, suggesting the close association of O(2)(-) with TNFalpha induction. NAC strongly depressed phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), which is necessary for inducing TNFalpha in microglia. On the other hand, an O(2)(-) donor, 3-(4-Morpholinyl)sydnonimine (SIN-1), induced TNFalpha in microglia, and the effects of SIN-1 were completely abolished in the presence of superoxide dismutase. There is little likelihood that the NO produced in SIN-1 degradation induces TNFalpha in microglia, because TNFalpha was not induced in microglia exposed to the NO-donor S-nitroso-N-acetyl-dl-penicillamine. Moreover, the addition of SIN-1 to microglia resulted in activation of p38 MAPK and its upstream kinase MKK3/6. Taken together, these results showed that O(2)(-) is an important signaling molecule for activating the MKK3/6-p38 cascade, which is requisite for inducing TNFalpha in microglia. PMID- 21981806 TI - eFurniture for home-based frailty detection using artificial neural networks and wireless sensors. AB - The purpose of this study is to integrate wireless sensor technologies and artificial neural networks to develop a system to manage personal frailty information automatically. The system consists of five parts: (1) an eScale to measure the subject's reaction time; (2) an eChair to detect slowness in movement, weakness and weight loss; (3) an ePad to measure the subject's balancing ability; (4) an eReach to measure body extension; and (5) a Home-based Information Gateway, which collects all the data and predicts the subject's frailty. Using a furniture-based measuring device to provide home-based measurement means that health checks are not confined to health institutions. We designed two experiments to obtain optimum frailty prediction model and test overall system performance: (1) We developed a three-step process to adjust different parameters to obtain an optimized neural identification network whose parameters include initialization, L.R. dec and L.R. inc. The post-process identification rate increased from 77.85% to 83.22%. (2) We used 149 cases to evaluate the sensitivity and specificity of our frailty prediction algorithm. The sensitivity and specificity of this system are 79.71% and 86.25% respectively. These results show that our system is a high specificity prediction tool that can be used to assess frailty. PMID- 21981805 TI - Neurons identified by NeuN/Fox-3 immunoreactivity have a novel distribution in the hamster and mouse suprachiasmatic nucleus. AB - The suprachiasmatic nucleus (SCN) has several structural characteristics and cell phenotypes shared across species. Here, we describe a novel feature of SCN anatomy that is seen in both hamster and mouse. Frozen sections through the SCN were obtained from fixed brains and stained for the presence of immunoreactivity to neuronal nuclear protein (NeuN-IR) using a mouse monoclonal antibody which is known to exclusively identify neurons. NeuN-IR did not identify all SCN neurons as medial NeuN-IR neurons were generally not present. In the hamster, NeuN-IR cells are present rostrally, scattered in the dorsal half of the nucleus. More caudally, the NeuN-IR cells are largely, but not exclusively, scattered inside the lateral and dorsolateral border. At mid- to mid-caudal SCN levels, a dense group of NeuN-IR cells extends from the dorsolateral border ventromedially to encompass the central subnucleus of the SCN (SCNce). The pattern is similar in the mouse SCN. NeuN-IR does not co-localize with either cholecystokinin- or vasoactive intestinal polypeptide, but does with vasopressin-IR in the caudal SCN. In the hamster SCNce, numerous cells contain both calbindin- and NeuN-IR. The distribution of NeuN-IR cells in the SCN is unique, especially with regard to its generally lateral location through the length of the nucleus. The distribution of NeuN-IR cells is not consistent with most schemas representing SCN organization or with terminology referring to its widely accepted subdivisions. NeuN has recently been identified as Fox-3 protein. Its function in the SCN is not known, nor is it known why a large proportion of SCN cells do not contain NeuN-IR. PMID- 21981807 TI - Reproducibility of IVUS border detection for carotid atherosclerotic plaque assessment. AB - Plaque composition is a potentially important diagnostic feature for carotid artery stenting (CAS). The purpose of this investigation is to evaluate the reproducibility of manual border correction in intravascular ultrasound with virtual histology (VH IVUS) images. Three images each were obtained from 51 CAS datasets on which automatic border detection was corrected manually by two trained observers. Plaque was classified using the definitions from the CAPITAL (Carotid Artery Plaque Virtual Histology Evaluation) study, listed in order from least to most pathological: no plaque, pathological intimal thickening, fibroatheroma, fibrocalcific, calcified fibroatheroma, thin-cap fibroatheroma, and calcified thin-cap fibroatheroma. Inter-observer variability was quantified using both weighted and unweighted Kappa statistics. Bland-Altman analysis was used to compare the cross-sectional areas of the vessel and lumen. Agreement using necrotic core percentage as the criterion was evaluated using the unweighted Kappa statistic. Agreement between classifications of plaque type was evaluated using the weighted Kappa statistic. There was substantial agreement between the observers based on necrotic core percentage (kappa=0.63), while the agreement was moderate (kappa(quadratic)=0.60) based on plaque classification. Due to the time-consuming nature of manual border detection, an improved automatic border detection algorithm is necessary for using VH IVUS as a diagnostic tool for assessing the suitability of patients with carotid artery occlusive disease for CAS. PMID- 21981808 TI - Circulating endothelial progenitor cells and large artery structure and function in young subjects with uncomplicated type 1 diabetes. AB - BACKGROUND: Carotid intima-media thickness (IMT), indices of large artery stiffness and measures of endothelium function may be used as markers of early atherosclerosis in type 1 diabetes mellitus (T1DM). The aim of the present study was to compare the indices of large artery structure and function as well as endothelial function and regenerating capacity between adolescents with T1DM and healthy control of similar age. In addition, the associations of different vascular measures with endothelial progenitor cells (EPCs), glyco-metabolic control and serum levels of advanced glycation endproducts (AGEs), soluble receptors for AGEs (sRAGE) and adiponectin were evaluated. METHODS: Sixteen uncomplicated young T1DM patients (mean age 18 +/- 2 years, history of disease 11 +/- 5 years, HbA1c 7.7 +/- 1.1%) and 26 controls (mean age 19 +/- 2 years) were studied. A radiofrequency-based ultrasound system (Esaote MyLab 70) was used to measure carotid IMT and wave speed (WS, index of local stiffness), applanation tonometry (PulsePen) was applied to obtain central pulse pressure (PP) and augmentation index (AIx), and carotid-femoral pulse wave velocity (PWV, Complior) was used as index of aortic stiffness. Peripheral endothelium-dependent vasodilation was determined as reactive hyperemia index (RHI, EndoPAT). Circulating EPCs, glycometabolic profile, AGEs (autofluorescence method), sRAGE and adiponectin were also measured. RESULTS: After adjusting for age, sex and blood pressure, T1DM adolescents had significantly higher carotid IMT (456 +/- 7 vs. 395 +/- 63 MUm, p < 0.005), carotid WS (p < 0.005), PWV (p = 0.01), AIx (p < 0.0001) and central PP (p < 0.01) and lower EPCs (p = 0.02) as compared to controls. RHI was reduced only in diabetic patients with HbA1c >=7.5% (p < 0.05). In the overall population, EPCs were an independent determinant of carotid IMT (together with adiponectin), while fasting plasma glucose was an independent determinant of carotid WS, AIx and central PP. CONCLUSIONS: Our findings suggest that young subjects with relatively long-lasting T1DM have a generalized preclinical involvement of large artery structure and function, as well as a blunted endothelium regenerating capacity. Hyperglycemia and suboptimal chronic glycemic control seem to deteriorate the functional arterial characteristics, such as large arteries stiffness, wave reflection and peripheral endothelium dependent vasodilation, whereas an impaired endothelium regenerating capacity and adiponectin levels seem to influence arterial structure. PMID- 21981810 TI - Gender differences in morphometric properties of muscle fibres measured on cross sections of rat hindlimb muscles. AB - The study was aimed at demonstrating gender differences in the numbers, diameters and cross-section areas of muscle fibres for three hindlimb skeletal muscles responsible for locomotion and maintenance of body posture: soleus, tibialis anterior and flexor digitorum brevis in rats. The experiments were performed on five 6-month-old male and female Wistar rats. In both genders, all studied muscles of the right and left hindlimbs were isolated from surrounding tissues and excised for further procedures. The muscle transverse cross-sections taken from the muscle mid-belly were analysed. Following staining of reticular fibres by silver impregnation, the numbers, diameters and cross-section areas of muscle fibres were determined from microscopic images of muscle sections. The body mass of male rats was 80% higher than that of females. In addition, the muscle mass and the cross-section area were 53-82 and 26-45% higher in males, respectively. The number of muscle fibres was 11-42% higher in males than in females whereas the fibre diameters were 7-29% higher in males. The most conspicuous differences between males and females were found with respect to tibialis anterior, whereas the smallest differences were evident in soleus. The present study revealed that the gender morphometric differences in the studied rat hindlimb muscles were mainly owing to differences in number and size of muscle fibres and that the difference in muscle mass could be explained mainly from higher number of muscle fibres in males and to smaller degree from their larger diameters. PMID- 21981809 TI - Metabolic and hedonic drives in the neural control of appetite: who is the boss? AB - Obesity is on the rise in all developed countries, and a large part of this epidemic has been attributed to excess caloric intake, induced by ever present food cues and the easy availability of energy dense foods in an environment of plenty. Clearly, there are strong homeostatic regulatory mechanisms keeping body weight of many individuals exposed to this environment remarkably stable over their adult life. Other individuals, however, seem to eat not only because of metabolic need, but also because of excessive hedonic drive to make them feel better and relieve stress. In the extreme, some individuals exhibit addiction like behavior toward food, and parallels have been drawn to drug and alcohol addiction. However, there is an important distinction in that, unlike drugs and alcohol, food is a daily necessity. Considerable advances have been made recently in the identification of neural circuits that represent the interface between the metabolic and hedonic drives of eating. We will cover these new findings by focusing first on the capacity of metabolic signals to modulate processing of cognitive and reward functions in cortico-limbic systems (bottom-up) and then on pathways by which the cognitive and emotional brain may override homeostatic regulation (top-down). PMID- 21981811 TI - Use of a mechanical lithotripter to aid in the removal of an impacted razor blade in the esophagus. PMID- 21981812 TI - Endoscopic placement of permanent indwelling transmural stents in disconnected pancreatic duct syndrome: does benefit outweigh the risks? PMID- 21981813 TI - Forward-viewing versus oblique-viewing echoendoscopes in transluminal drainage of pancreatic fluid collections: a multicenter, randomized, controlled trial. AB - BACKGROUND: EUS-guided drainage of pancreatic fluid collections (PFCs) is commonly performed with oblique-viewing echoendoscopes. However, accessing the PFC under an oblique angle can make drainage difficult. These difficulties might be overcome by using a forward-viewing echoendoscope. OBJECTIVE: To compare endoscopic PFC drainage with an oblique-viewing versus a forward-viewing echoendoscope with emphasis on ease of endoscopic drainage. DESIGN: Multicenter, randomized, controlled trial. SETTING: Four tertiary-care referral centers. PATIENTS: This study involved 58 patients with PFCs. INTERVENTION: Patients with PFCs (>= 6 cm) in whom drainage was indicated were randomized to receive EUS guided drainage with a forward-viewing echoendoscope or an oblique-viewing echoendoscope. In cases of failed drainage, patients were crossed over to the other study arm. MAIN OUTCOME MEASUREMENTS: Ease of EUS-guided drainage measured by procedure time. Secondary endpoints included technical success, EUS endoscope preference, clinical success, and adverse events. RESULTS: Fifty-eight consecutive patients underwent randomization, of whom 52 were available for primary endpoint analysis. All 26 EUS-guided procedures done with the oblique viewing echoendoscope and 24 of the 26 procedures done with the forward-viewing echoendoscope were technically successful. Mean (+/- standard deviation) procedure time was 24:55 +/- 9:58 minutes in the forward-viewing echoendoscope group and 27:04 +/- 9:58 minutes in the oblique-viewing echoendoscope group (P = .44). Median overall procedure ease was graded as equal (easy) in both groups. Drainage-related adverse events occurred in 2 patients (8%) in the forward viewing echoendoscope group versus none in the oblique-viewing echoendoscope group (P = .56). Overall clinical success was achieved in 82% of patients (95% confidence interval, 69%-91%). LIMITATIONS: Derived main outcome parameter and highly specialized endoscopists in tertiary-care referral centers. CONCLUSION: This multicenter, randomized, controlled trial comparing the performance of oblique-viewing echoendoscopes and forward-viewing echoendoscopes in draining PFCs did not show a difference in ease of EUS-guided drainage or procedure safety and efficacy between the forward-viewing echoendoscope and the oblique-viewing echoendoscope. Clinical success was achieved in 82% of patients. PMID- 21981814 TI - Efficacy of full-thickness GI perforation closure with a novel over-the-scope clip application device: an animal study. AB - BACKGROUND: A novel, over-the-scope clip (OTSC) system may be suitable for closure of various GI perforations. The strength and maximum diameter of closure for a single OTSC, however, are unknown. OBJECTIVE: To determine the maximum closure capacity (diameter) and pressure threshold for a single OTSC. DESIGN: Prospective ex-vivo study. SETTING: Academic medical center. METHOD: Full thickness, standardized defects of 5 mm, 10 mm, 15 mm, 20 mm, and 25 mm were created in porcine stomachs. Similarly, full-thickness defects of 10 mm, 20 mm, 25 mm, 30 mm, and 35 mm were created in porcine colons. A single OTSC was endoscopically deployed 5 times for each full-thickness defect size in an ex-vivo endoscopic simulator. MAIN OUTCOME MEASUREMENTS: Each closure site was tested under water with compressed air for burst pressure. RESULTS: We achieved successful closure in all stomach defects ranging from 5 to 20 mm by using 12-mm OTSCs with short teeth and colon defects ranging from 10 to 30 mm with 14-mm OTSCs with short teeth. Mean (+/- standard deviation [SD]) burst pressures for the gastric closure sites were 74.9 +/- 17.5 mm Hg for 15-mm defects, 49.3 +/- 21.6 mm Hg for 20-mm defects, and 15.2 +/- 4.1 mm Hg for 25-mm defects. Mean (+/- SD) burst pressures for the colon closure sites were 117.9 +/- 40.1 mm Hg for 20 mm defects, 57.4 +/- 4.2 mm Hg for 30-mm defects, and 10.9 +/- 7.6 mm Hg for 35 mm defects. LIMITATIONS: Ex-vivo study, does not reflect difficult locations. CONCLUSION: Full-thickness tissue defects ranging from 5 to 20 mm in the stomach and from 10 to 30 mm in the colon can be closed adequately with a single OTSC in an ex-vivo experimental setting. Tissue defects larger than 20 mm in the stomach and 30 mm in the colon may require more than one OTSC or supplemental endoclips to achieve adequate closure. Endoscopic inspection of the closure site does not assure adequate closure of larger perforations. PMID- 21981815 TI - Extracorporeal shock wave lithotripsy with a transportable mini-lithotripter and subsequent endoscopic treatment improves clinical outcome in obstructive calcific chronic pancreatitis. AB - BACKGROUND: Extracorporeal shock wave lithotripsy (ESWL) of pancreatic duct stones followed by ERCP with mechanical clearance of the pancreatic duct and subsequent stenting is an established treatment option for chronic calcific pancreatitis. OBJECTIVE: To test the efficacy of a modified transportable mini lithotripter for ESWL of pancreatic duct stones. DESIGN: Prospective single center study. SETTING: University hospital. PATIENTS: This study involved 32 patients with obstructive chronic calcific pancreatitis and pain in whom previous endoscopic stone removal and pancreatic duct decompression had failed. INTERVENTIONS: ESWL followed by ERCP for stone clearance of the pancreatic duct and mechanical removal of stones or stenting. MAIN OUTCOME MEASUREMENTS: Endoscopic duct clearance and/or stent insertion, pain and quality-of-life scores. RESULTS: A median of 4 ESWL sessions (interquartile range 2.75-8.5) with a median of 6800 shock waves (4225-15,425) were required. Pain relief after ESWL only was noted in 24 patients (75.0%), whereas no change in the intensity of pain was reported by 7 patients (21.9%), and pain was worse in 1 patient. All patients underwent ERCP and stent placement, resulting in complete resolution of pain in 17 patients (53.1%) and pain improvement in 28 patients (87.5%). The quality-of life score was significantly improved after ESWL and endoscopic clearance or stenting in all patients. LIMITATIONS: Uncontrolled study. CONCLUSIONS: ESWL with the mini-lithotripter results in fragmentation of pancreatic duct calculi. ESWL in conjunction with endoscopic clearance of the pancreatic duct and stenting is associated with significant improvement in clinical outcome and quality of life in patients with obstructive calcific chronic pancreatitis. PMID- 21981816 TI - Immunoglobulin G4-related inflammatory pseudotumor of the stomach. PMID- 21981818 TI - Remodeling of mitochondrial interior in cardiac lipofuscinosis. AB - Ultrastructural analysis was performed in cardiac ceroidlipofuscinosis to confirm the presence and the nature of storage material. Granular osmophilic deposits characteristic of GROD structures coincidented with particularly aberrant mitochondria. Remodeling of mitochondrial interior with the appearance of several form of abnormal inclusions was never observed in cardiac ceroidlipofuscinosis. The presence of dense osmophilic bodies, glycogen conglomerates, balloon-like and onion-like structures in mitochondrial interior seem to be early events of this storage process. PMID- 21981817 TI - Retrospective examination of injuries and physical fitness during Federal Bureau of Investigation new agent training. AB - BACKGROUND: A retrospective examination was conducted of injuries, physical fitness, and their association among Federal Bureau of Investigation (FBI) new agent trainees. METHODS: Injuries and activities associated with injuries were obtained from a review of medical records in the medical clinic that served the new agents. A physical fitness test (PFT) was administered at Weeks 1, 7 and 14 of the 17-week new agent training course. The PFT consisted of push-ups, sit-ups, pull-ups, a 300-meter sprint, and a 1.5-mile run. Injury data were available from 2000 to 2008 and fitness data were available from 2004 to early 2009. RESULTS: During the survey period, 37% of men and 44% of women experienced one or more injuries during the new agent training course (risk ratio (women/men) = 1.18, 95% confidence interval = 1.07-1.31). The most common injury diagnoses were musculoskeletal pain (not otherwise specified) (27%), strains (11%), sprains (10%), contusions (9%), and abrasions/lacerations (9%). Activities associated with injury included defensive tactics training (48%), physical fitness training (26%), physical fitness testing (6%), and firearms training (6%). Over a 6-year period, there was little difference in performance of push-ups, sit-ups, pull ups, or the 300-meter sprint; 1.5-mile run performance was higher in recent years. Among both men and women, higher injury incidence was associated with lower performance on any of the physical fitness measures. CONCLUSION: This investigation documented injury diagnoses, activities associated with injury, and changes in physical fitness, and demonstrated that higher levels of physical fitness were associated with lower injury risk. PMID- 21981819 TI - Antisense oligonucleotide targeting matrix metalloproteinase-7 (MMP-7) changes the ultrastructure of human A549 lung adenocarcinoma cells. AB - Antisense oligonucleotide (ASODN) targeting specific gene can be capable of potently downregulating proliferation and invasion in human cancer cells. However, the underlying mechanisms are less well defined. Here the authors show that matrix metalloproteinase-7 (MMP-7) ASODN changes the ultrastructure of human A549 lung adenocarcinoma cells. Transfection of MMP-7 ASODN significantly lowered the expression of MMP-7 protein in A549 cells. Decreased microvilli, endoplasmic reticulum dilation, swelling of mitochondria, and formation of apoptotic bodies were observed by transmission electron microscope. Collectively, the findings identified the morphological mechanism that MMP-7 ASODN inhibited proliferation and invasion in A549 cells. PMID- 21981820 TI - Ultrastructural analysis of the oocytes of female Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae) ticks subjected to the action of Azadirachta indica A. Juss (neem). AB - The present study provides ultrastructural information about the acaricidal effects of neem (Azadirachta indica A. Juss) on the ovaries of R. sanguineus engorged females. In general, the main damage caused in the oocytes was alteration in the shape of the cell and of the germinal vesicle, ring-shaped nucleolus, cytoplasmic vacuolation, and disorganization of the organelles and of the cell membranes (including the chorion), all of which indicate that these cells could be in the process of death. The results showed that azadirachtin would be an efficient acaricide agent for inhibiting and/or neutralizing the reproduction process of R. sanguineus females, impairing the reproductive ability of this species. PMID- 21981821 TI - Prevalence of fibromyalgia in France: a multi-step study research combining national screening and clinical confirmation: The DEFI study (Determination of Epidemiology of FIbromyalgia). AB - BACKGROUND: Fibromyalgia is a common disease, but little is known on its real prevalence in France. This epidemiological study aimed to assess fibromyalgia (FM) prevalence in the French metropolitan population, based on a multi-step sampling analysis, combining national screening and clinical confirmation by trained specialists. METHODS: a sampling method on the entire national territory was used: patients over 18 years of age accepting to take part in the study were contacted by telephone using the LFES Questionnaire, a screening test for FM. The, for patients detected by the LFESQ, a visit with a FM-trained rheumatologist was proposed to confirm FM, based on 1990 ACR criteria. Each detected patient completed the following self-questionnaires: SF36, HADS, stress VAS, Co morbidities and Regional pain score. RESULTS: 3081 patients were contacted in 5 representative French regions, of which 232 patients were screened for FM. A fibromyalgia diagnosis was then confirmed by rheumatologist in 20 cases (17 female and 3 male, 56.9 +/- 13.2 years). The final estimated FM prevalence was 1.6 (CI95: 1.2%; 2.0%). No significant difference was detected between the patients accepting (CS+) and refusing (CS-) rheumatologist visit for the SF36 score, regional pain score, stress VAS scale and co-morbidities. In patients detected for FM by the LFESQ, we found a statistically significant decrease in quality of life and a statistically significant increase in stress level in patients with a confirmed diagnosis (FM+) (6.3 +/- 1.9) compared to patients with an invalidated diagnosis (FM-) (4.4 +/- 2.8; p = 0.007). The study also demonstrated a significant association, independently of ACR criteria, between the diagnosis of FM and several factors such as regional pain score > 10, elevated stress level, low SF36 scale score and presence of gastro-intestinal disorder co-morbidities. CONCLUSION: Fibromyalgia is a common condition; the 1.6% prevalence calculated in the French population in our study corroborates the figures published in the European literature. Our results also suggest that criteria such as regional pain score, stress level or SF36 quality of life, could represent useful tools in fibromyalgia diagnosis. PMID- 21981822 TI - Development of a fast instrumental method for the analysis of pharmaceuticals in environmental and wastewaters based on ultra high performance liquid chromatography (UHPLC)-tandem mass spectrometry (MS/MS). AB - This work describes the development, optimization and validation of an analytical method for the simultaneous detection and identification of 74 pharmaceutically active compounds (PhACs), from various therapeutic groups, in both environmental (ground and surface water) and wastewaters (WW). The method is based on the simultaneous extraction of all target compounds by solid phase extraction (SPE), using a hydrophilic-lipophilic balanced polymer followed by ultra high performance liquid chromatography (UHPLC) tandem mass spectrometry (MS/MS). Two selected reaction monitoring (SRM) transitions have been monitored per compound in order to fulfil the EC guidelines, as well as to ensure an accurate identification of target compounds in the samples. Quantification is performed by internal standard approach, applying 24 specific isotopically labeled compounds. The main advantages of the developed method, besides the selectivity and reliability of the results, is its high throughput. All compounds are extracted in a single step and the instrumental analysis lasts 5 min (NI mode)+8 min (PI mode), allowing fast throughput of samples. The limits of detection range from 0.01 to 50 ng L(-1), depending on the matrix, for most of the compounds. Finally, the method developed has been applied to the analysis of pharmaceuticals in the Ebro river basin (NE Spain). PMID- 21981823 TI - Response to issues on GM agriculture in Africa: Are transgenic crops safe? AB - The controversies surrounding transgenic crops, often called Genetically Modified Organisms (GMOs), call for a need to raise the level of public awareness of Genetic Modification (GM) technology in Africa. This should be accomplished by educating the public about the potential benefits and risks that may be associated with this new technology. In the last 15 years, GM crop producing countries have benefited from adoption of this new technology in the form of improved crop productivity, food security, and quality of life. The increased income to resource-poor farmers is a key benefit at the individual level especially as most countries using this technology are in the developing world, including three African countries (South Africa, Burkina Faso and Egypt). Despite clear benefits to countries and farmers who grow GMOs, many people are concerned about suspected potential risks associated with GMOs. This sparks debate as to whether GM technology should be adopted or not. Given the concerns regarding the safety of GMO products, thorough scientific investigation of safe application of GMOs is required. The objective of this paper is to respond to the issues of GM agriculture in Africa and some of the issues surrounding the adoption of GM crops between developed and developing countries. In this article, I analyse relevant papers relating to the adoption of GM technology particularly in developing countries including the few African countries that have adopted GM crops. The issues discussed span a wide range including: safety; potential benefits and risks; disputes between the United States of America (USA) and the European Union (EU) over adoption of GM crops with a focus on Africa continent. This article is concluded by summarising the issues raised and how GM technology can be adopted for agricultural development in Africa. PMID- 21981824 TI - Impulsivity and alcohol consumption in young social drinkers. AB - Impulsivity may have different facets that contribute to drinking patterns in young people. This research examined how aspects of impulse control, especially the ability to inhibit a response, predicted recent alcohol use patterns in young social drinkers. Participants (N=109) between the ages of 18 and 21 performed a cued go/no-go task that required quick responses to go targets and the inhibition of responses to no-go targets. Participants also completed several questionnaires that assessed drinking habits (TLFB) and self-reported impulsivity (BIS-11). Regression analyses revealed that both the impulsivity questionnaire scores and the inhibitory failures observed on the behavioral task predicted various aspects of recent drinking. However, only the inhibitory failures from the behavioral task, and not the impulsivity questionnaire scores, predicted the highest number of drinks consumed on one occasion during the past month. These findings are consistent with the notion that impulsivity may have different components that may be contributing the drinking patterns, and this research suggests that the inability to withhold a response is a strong predictor of the binge use of alcohol. PMID- 21981825 TI - RhIG for the treatment of immune thrombocytopenia: consensus and controversy (CME). AB - Anti-D immune globulin (RhIG) is a front-line option in North America for the treatment of immune thrombocytopenia (ITP) in children and adults. Recently, addition of a Food and Drug Administration-mandated black box warning highlighted the risks of intravascular hemolysis, renal failure, and disseminated intravascular coagulation after anti-D infusion, prompting concern within the medical community regarding its use. A working group convened in response to this warning to prepare a consensus document regarding the safety of RhIG because there has been no increased incidence of adverse events since the initial discovery of these reactions many years ago. The efficacy of anti-D is well documented and only briefly reviewed. The estimated incidence and proposed mechanisms for the rare, major treatment-related complications are discussed, and signal detection data associated with heightened risk of acute hemolytic reactions are presented. The importance of considering host factors, given the rarity of severe reactions, is emphasized. Safety profiles of parallel treatment options are reviewed. The working group consensus is that RhIG has comparable safety and efficacy to other front-line agents for the treatment of children and adults with ITP. Safety may be further improved by careful patient selection. PMID- 21981826 TI - Genome-wide identification and characterization of ATP-binding cassette transporters in the silkworm, Bombyx mori. AB - BACKGROUND: The ATP-binding cassette (ABC) transporter superfamily is the largest transporter gene family responsible for transporting specific molecules across lipid membranes in all living organisms. In insects, ABC transporters not only have important functions in molecule transport, but also play roles in insecticide resistance, metabolism and development. RESULTS: From the genome of the silkworm, Bombyx mori, we have identified 51 putative ABC genes which are classified into eight subfamilies (A-H) by phylogenetic analysis. Gene duplication is very evident in the ABCC and ABCG subfamilies, whereas gene numbers and structures are well conserved in the ABCD, ABCE, ABCF, and ABCH subfamilies. Microarray analysis revealed that expression of 32 silkworm ABC genes can be detected in at least one tissue during different developmental stages, and the expression patterns of some of them were confirmed by quantitative real-time PCR. A large number of ABC genes were highly expressed in the testis compared to other tissues. One of the ABCG genes, BmABC002712, was exclusively and abundantly expressed in the Malpighian tubule implying that BmABC002712 plays a tissue-specific role. At least 5 ABCG genes, including BmABC005226, BmABC005203, BmABC005202, BmABC010555, and BmABC010557, were preferentially expressed in the midgut, showing similar developmental expression profiles to those of 20-hydroxyecdysone (20E)-response genes. 20E treatment induced the expression of these ABCG genes in the midgut and RNA interference mediated knockdown of USP, a component of the 20E receptor, decreased their expression, indicating that these midgut-specific ABCG genes are 20E-responsive. CONCLUSION: In this study, a genome-wide analysis of the silkworm ABC transporters has been conducted. A comparison of ABC transporters from 5 insect species provides an overview of this vital gene superfamily in insects. Moreover, tissue- and stage-specific expression data of the silkworm ABCG genes lay a foundation for future analysis of their physiological function and hormonal regulation. PMID- 21981827 TI - The Aspergillus niger multicopper oxidase family: analysis and overexpression of laccase-like encoding genes. AB - BACKGROUND: Many filamentous fungal genomes contain complex groups of multicopper oxidase (MCO) coding genes that makes them a good source for new laccases with potential biotechnological interest. A bioinformatics analysis of the Aspergillus niger ATCC 1015 genome resulted in the identification of thirteen MCO genes. Ten of them were cloned and homologously overexpressed. RESULTS: A bioinformatic analysis of the A. niger ATCC 1015 genome revealed the presence of 13 MCO genes belonging to three different subfamilies on the basis of their phylogenetic relationships: ascomycete laccases, fungal pigment MCOs and fungal ferroxidases. According to in silico amino acid sequence analysis, the putative genes encoding for functional extracellular laccases (mcoA, mcoB, mcoC, mcoD, mcoE, mcoF, mcoG, mcoI, mcoJ and mcoM) were placed under the control of the glaA promoter and overexpressed in A. niger N593. Enzyme activity plate assays with several common laccase substrates showed that all genes are actually expressed and code for active MCOs. Interestingly, expressed enzymes show different substrate specificities. In addition, optimization of fungal pigment MCOs extracellular production was investigated. The performance of the widely used glucoamylase signal sequence (ssGlaA) in McoA secretion was studied. Results obtained suggest that ssGlaA do not yield higher levels of secreted McoA when compared to its native secretion signal. Also, McoB synthesis was investigated using different nitrogen sources in minimal medium liquid cultures. Higher yields of extracellular McoB were achieved with (NH4)2 tartrate. CONCLUSIONS: Aspergillus niger is a good source of new laccases. The different substrate specificity observed in plate assays makes them interesting to be purified and biochemically compared. The homologous signal sequence of McoA has been shown to be a good choice for its extracellular overexpression. From the nitrogen sources tested (NH4)2 tartrate has been found to be the most appropriate for McoB production in A. niger. PMID- 21981829 TI - Expertise in complex decision making: the role of search in chess 70 years after de Groot. AB - One of the most influential studies in all expertise research is de Groot's (1946) study of chess players, which suggested that pattern recognition, rather than search, was the key determinant of expertise. Many changes have occurred in the chess world since de Groot's study, leading some authors to argue that the cognitive mechanisms underlying expertise have also changed. We decided to replicate de Groot's study to empirically test these claims and to examine whether the trends in the data have changed over time. Six Grandmasters, five International Masters, six Experts, and five Class A players completed the think aloud procedure for two chess positions. Findings indicate that Grandmasters and International Masters search more quickly than Experts and Class A players, and that both groups today search substantially faster than players in previous studies. The findings, however, support de Groot's overall conclusions and are consistent with predictions made by pattern recognition models. PMID- 21981828 TI - Rapid onset vasodilatation is blunted in obese humans. AB - AIM: Conduit artery function in obese humans is frequently assessed at rest, but very little is known about resistance artery function in response to muscle contraction. We tested the hypothesis that obese adults will exhibit reduced contraction-induced rapid onset vasodilatation. Single and brief forearm contractions were used to isolate the local effects of muscle contraction on the forearm vasodilatory response, independent of systemic haemodynamic and sympathetic neural influence. METHODS: We measured forearm blood flow (Doppler ultrasound), blood pressure (finger photoplethysmography) and heart rate (electrocardiogram) on a beat-by-beat basis in 14 obese (body mass index = 36.2 +/- 1.7 kg m(-2)) and 14 lean (body mass index = 21.6 +/- 0.7 kg m(-2)) young (18 40 years) adults. Percent changes from baseline in forearm vascular conductance (FVC(%) ) were calculated in response to single, brief forearm contractions performed in random order at 15, 20, 25, 30, 40 and 50% of maximal voluntary contraction (MVC). RESULTS: In both groups, each single contraction evoked a significant (P < 0.05), immediate (within one cardiac cycle) and graded FVC(%) increase from one up to six cardiac cycles post-contraction. Immediate (20-50% MVC), peak (15-50% MVC) and total (area under the curve, 20-50% MVC) vasodilatory responses were reduced with obesity. The degree of impaired vasodilatation increased with increasing workloads. CONCLUSIONS: These novel findings demonstrate a blunted contraction-induced rapid onset vasodilatation with obesity that is exercise intensity dependent. Impaired rapid onset vasodilatation may negatively impact haemodynamic responses to everyday intermittent activities performed by obese humans. PMID- 21981830 TI - Intra-articular fractures of the distal radius evaluated by computed tomography. AB - PURPOSE: To describe the fracture lines of intra-articular distal radius fractures as evaluated by computed tomography scans. METHODS: With computed tomography, we examined 95 intra-articular fractures of the distal radius from 91 patients. Multiplanar computed tomography images or 3-dimensional images, or both, were assessed. We divided the periphery of the distal articular surface of the distal radius into 6 segments (sigmoid notch, dorsoulnar, dorsoradial, volar radial, volar ulnar, radial styloid) and examined which segment had fracture lines. For fractures involving the sigmoid notch, we divided them by the location and the direction of the fracture lines entering the sigmoid notch. Next, we categorized the fractures into 3 fracture groups (extension group, neutral group, and flexion group) by the dorsal or volar angulation of the cortex of the distal radius. In all the fractures and in each of the 3 fracture groups, we described the frequency of the fracture lines in each segment and the number of the segments with fracture lines. The location and the direction of the fracture lines in the sigmoid notch were analyzed in each of the 3 fracture groups. RESULTS: The most frequent fracture type, seen in 21% of all fractures, had fracture lines in the sigmoid notch and the dorsoulnar segment. The frequency of the fracture lines was 77% in the sigmoid notch, 71% in the dorsoulnar segment, and 57% in the dorsoradial segment. The volar ulnar segment was lowest in frequency, at 13%. The fractures in the extension group were more common in the dorsoulnar segment and less common in the dorsoradial segment and the radial styloid segment. The scaphoid facet always had a fracture in the flexion or neutral group. In the extension group, the direction of the fracture lines from the sigmoid notch was dorsoradial or parallel to the volar articular edge. In contrast, the direction was parallel or volar radial compared to the volar articular edge in the flexion group. CONCLUSIONS: We documented the location and the direction of intra-articular fracture lines of the distal radius. The location and the direction of fractures showed different tendencies related to the volar/dorsal angulation of the distal radius. CLINICAL RELEVANCE: The findings might help in the evaluation, classification, and treatment of intra articular fractures of the distal radius. PMID- 21981832 TI - SNAP-23 and syntaxin-3 are required for chemokine release by mature human mast cells. AB - Mast cells play a key role in allergic and non-allergic disease by releasing a broad array of mediators. Soluble N-ethyl-maleimide-sensitive factor attachment protein receptors (SNAREs) are necessary for membrane fusion events during mast cell exocytosis. We have shown recently that the SNAREs SNAP-23, syntaxin (STX) 4, vesicle associated membrane protein (VAMP)-7, and VAMP-8 are required for release of pre-stored histamine by mast cells. Here we analyze the involvement of different SNARE isoforms in exocytosis of de novo synthesized chemokines in mast cells isolated from human intestine. Following IgE receptor cross-linking, mast cells released substantial amounts of the chemokines CXCL8, CCL2, CCL3, and CCL4. Measurement of SNARE mRNA expression revealed only a moderate up-regulation of mRNA for STX-4 after stimulation for 1.5h. Inhibition of SNAP-23 or STX-3 abolished IgE mediated release of the chemokines CXCL8, CCL2, CCL3, and CCL4. In contrast, blocking of STX-2, or VAMP-3 did not affect the chemokine release. Inhibition of STX-4 or VAMP-8 resulted in a reduced release of CXCL8, but not of CCL2, CCL3, or CCL4. Inhibition of STX-6 attenuated the release of CXCL8 and CCL2, inhibition of VAMP-7 that of CCL3. In summary, STX-3 and SNAP-23 are crucial for the release of all chemokines in mature human mast cells whereas other SNAREs affect only release of selected chemokines. PMID- 21981831 TI - Cost-effectiveness of open partial fasciectomy, needle aponeurotomy, and collagenase injection for dupuytren contracture. AB - PURPOSE: We undertook a cost-utility analysis to compare traditional fasciectomy for Dupuytren with 2 new treatments, needle aponeurotomy and collagenase injection. METHODS: We constructed an expected-value decision analysis model with an arm representing each treatment. A survey was administered to a cohort of 50 consecutive subjects to determine utilities of different interventions. We conducted multiple sensitivity analyses to assess the impact of varying the rate of disease recurrence in each arm of the analysis as well as the cost of the collagenase injection. The threshold for a cost-effective treatment is based on the traditional willingness-to-pay of $50,000 per quality-adjusted life years (QALY) gained. RESULTS: The cost of open partial fasciectomy was $820,114 per QALY gained over no treatment. The cost of needle aponeurotomy was $96,474 per QALY gained versus no treatment. When we performed a sensitivity analysis and set the success rate at 100%, the cost of needle aponeurotomy was $49,631. When needle aponeurotomy was performed without surgical center or anesthesia costs and with reduced hand therapy, the cost was $36,570. When a complete collagenase injection series was priced at $250, the cost was $31,856 per QALY gained. When the injection series was priced at $945, the cost was $49,995 per QALY gained. At the market price of $5,400 per injection, the cost was $166,268 per QALY gained. CONCLUSIONS: In the current model, open partial fasciectomy is not cost effective. Needle aponeurotomy is cost-effective if the success rate is high. Collagenase injection is cost-effective when priced under $945. TYPE OF STUDY/LEVEL OF EVIDENCE: Economic and Decision Analysis II. PMID- 21981833 TI - Framingham Heart Study. PMID- 21981835 TI - Clinical utility of inflammatory markers and advanced lipoprotein testing: advice from an expert panel of lipid specialists. AB - The National Cholesterol Education Program Adult Treatment Panel guidelines have established low-density lipoprotein cholesterol (LDL-C) treatment goals, and secondary non-high-density lipoprotein (HDL)-C treatment goals for persons with hypertriglyceridemia. The use of lipid-lowering therapies, particularly statins, to achieve these goals has reduced cardiovascular disease (CVD) morbidity and mortality; however, significant residual risk for events remains. This, combined with the rising prevalence of obesity, which has shifted the risk profile of the population toward patients in whom LDL-C is less predictive of CVD events (metabolic syndrome, low HDL-C, elevated triglycerides), has increased interest in the clinical use of inflammatory and lipid biomarker assessments. Furthermore, the cost effectiveness of pharmacological intervention for both the initiation of therapy and the intensification of therapy has been enhanced by the availability of a variety of generic statins. This report describes the consensus view of an expert panel convened by the National Lipid Association to evaluate the use of selected biomarkers [C-reactive protein, lipoprotein-associated phospholipase A(2), apolipoprotein B, LDL particle concentration, lipoprotein(a), and LDL and HDL subfractions] to improve risk assessment, or to adjust therapy. These panel recommendations are intended to provide practical advice to clinicians who wrestle with the challenges of identifying the patients who are most likely to benefit from therapy, or intensification of therapy, to provide the optimum protection from CV risk. PMID- 21981836 TI - The surprising AIM-HIGH results are not surprising when viewed through a particle lens. PMID- 21981837 TI - Interview with Dr. Scott Grundy during AHA EPI/NPAM meeting in March 2011. PMID- 21981838 TI - Statins and their influence on brain cholesterol. AB - BACKGROUND: Growing evidence suggests that different statins are able to lower brain cholesterol synthesis. It is not clear yet whether lipophilic statins influence brain cholesterol in different way than hydrophilic ones. SOURCES OF MATERIAL: The MEDLINE database. FINDINGS: According to the data reported thus far, statins may influence brain cholesterol metabolism directly (because they are able to penetrate BBB no matter whether they are hydrophilic or lipophilic) and also indirectly (by lowering plasma cholesterol). Although the definite mechanism is not known yet, it becomes obvious that statins do not only influence peripheral but also central cholesterol pool. CONCLUSION: Better understanding of the effects of statins on brain metabolism becomes more important because many studies bring evidence of a possible link between cholesterol and neurodegeneration. PMID- 21981839 TI - A survey on blood lipid levels among newborns and healthy inhabitants in urban Shanghai (2008-2009). AB - BACKGROUND: Dyslipidemia is considered one of the most important risk factors for coronary heart disease. OBJECTIVE: This study was designed to analyze the blood lipid levels of different age inhabitants in urban Shanghai in the 2000s and compare the results with those in the 1970s (1385 subjects), 1980s (3302 and 2399 subjects), and 1990s (3647 subjects). METHODS: Blood samples were collected from 2197 persons, as well as 200 newborns. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured. RESULTS: The TG level in adults >20 years of age was remarkably greater than those in the 1990s, but the TC level changed little and the LDL-C level apparently decreased. The mean HDL-C levels in adult women were similar to those in the 1970s and significantly greater by approximately 10 mg/dL than those in the 1990s (P < .001), whereas those in adult men >30 years of age were still low and were lower by about 10 mg/dL than the corresponding age groups in women. In adults aged 30-39, 40-49, and 50-59 years, the proportion of hypertriglyceridemia (TG levels >=200 mg/dL) was 18.24%, 17.96%, and 21.88% in men and 2.70%, 7.08%, and 8.55% in women, respectively. CONCLUSION: Currently, hypertriglyceridemia and low HDL-C in middle-aged men older than 30 years of age have become a growing problem. PMID- 21981840 TI - High-density lipoprotein cholesterol in diabetes: is higher always better? AB - BACKGROUND: Recent data suggest that highly elevated high-density lipoprotein cholesterol (HDL-C) may not always protect against cardiovascular disease. To what degree this is true in type 1 diabetes is unknown, although cardiovascular risk is increased despite elevated mean HDL-C. OBJECTIVE: To reassess the association between HDL-C and its subfractions with coronary artery disease (CAD) in childhood-onset type 1 diabetes. METHODS: Epidemiology of Diabetes Complications study participants free of CAD at baseline (301 men, 298 women; mean age, 27.1 and diabetes duration, 18.9 years) were studied. CAD was defined as angina, ischemic electrocardiogram changes, confirmed myocardial infarction, angiographic stenosis >=50%, revascularization, or CAD death. Cholesterol in the HDL fraction and HDL3 cholesterol subfraction was measured enzymatically after precipitation with heparin/manganese and dextran sulfate, respectively. RESULTS: During 18 years of follow-up, 29.5% of men and 25.5% of women developed CAD. Although a linear decrease in incidence was observed with increasing HDL-C concentration in men, incidence increased in women at less than 47 mg/dL and greater than 80 mg/dL. These patterns largely reflected the HDL3 cholesterol-CAD association. After multivariable adjustment, the linear, inverse, HDL-C/CAD association persisted in men (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.94-0.99); in women, the U-shaped relationship lost significance. HDL3 cholesterol remained multivariably associated with CAD in both men (linear association, P = .03) and women (HR 2.31 (95% CI 1.31-4.08) and HR 1.80 (95% CI 1.01-3.23) for the lowest and highest versus the middle quintiles, respectively). CONCLUSION: The increased CAD risk in women for an HDL-C >80 mg/dL in type 1 diabetes merits further study. Gender specificity could not be determined as only two men had HDL-C >80 mg/dL. PMID- 21981841 TI - Remnant-like particle cholesterol and serum amyloid A-low-density lipoprotein levels in obese subjects with metabolic syndrome. AB - BACKGROUND: Although the circulating levels of remnant-like particle cholesterol (RLP-C) or serum amyloid A-low-density lipoprotein (SAA-LDL) can individually be increased in subjects with metabolic syndrome (MetS), the correlation between the two markers has not yet been previously studied. In the present study, we aimed to investigate the correlation between RLP-C and SAA-LDL in obese subjects with MetS in comparison to those without MetS. METHODS: A total of 436 obese subjects were divided into groups with MetS and without MetS (male/female 75/143, mean age 49 years, current smokers 16% in both groups) by applying the age-, gender-, and smoking habit-matching method based on the database in the multicenter Japan Obesity and Metabolic Syndrome Study (JOMS). The data, including RLP-C and SAA LDL, were compared in each group. RESULTS: Significantly greater levels of RLP-C or SAA-LDL were observed in subjects with MetS in comparison with those without MetS. There was a significantly positive correlation between RLP-C and SAA-LDL, with a relatively greater correlation in subjects with MetS (coefficient = 0.290, P < .01) in comparison with those without MetS (coefficient = 0.181, P < .01). Multivariate-adjusted correlation analyses showed a greater correlation between RLP-C and SAA-LDL in subjects with MetS, relative to those without MetS, although the significant correlation decreased in both groups when the hypertriglyceridemic states were taken into account. CONCLUSIONS: A relatively greater and positive correlation between greater levels of RLP-C and SAA-LDL in obese subjects with MetS, in comparison with those without MetS, may be linked to the development of MetS-related cardiovascular disease. PMID- 21981842 TI - Effects of combination therapy with rosuvastatin and fenofibric acid in patients with mixed dyslipidemia and high-sensitivity C-reactive protein (>= 2 mg/L). cmb@bcm.tmc.edu. AB - BACKGROUND: Elevated levels of high-sensitivity C-reactive protein (hsCRP) correlate with an increased risk for cardiovascular events. Combination therapy with a statin and a fibrate may be more effective than statin monotherapy for reducing hsCRP, especially in patients with mixed dyslipidemia. OBJECTIVE: To characterize the treatment effects of rosuvastatin and fenofibric acid combination therapy compared with individual monotherapies in mixed dyslipidemic patients with baseline hsCRP >=2 mg/L versus <2 mg/L and to determine the effects of long-term treatment with rosuvastatin and fenofibric acid combination therapy on hsCRP and other lipids for patients with hsCRP >=2 mg/L after treatment with rosuvastatin monotherapy. METHODS: Data for the post hoc analysis were derived from two 12-week controlled studies and a 52-week extension study. Patients were treated with fenofibric acid 135 mg; rosuvastatin 5, 10, 20, or 40 mg; or rosuvastatin 5, 10, or 20 mg and fenofibric acid 135 mg in the controlled studies; and with rosuvastatin 20 mg and fenofibric acid 135 mg in the extension study. RESULTS: In this analysis, 65% (1416/2182) of patients had pretreatment baseline hsCRP >=2 mg/L. Among all treatment groups, larger decreases in hsCRP were observed in patients with greater baseline hsCRP; however, improvements in other lipids/apolipoprotein were comparable between the baseline hsCRP categories. Among patients with high hsCRP (>=2 mg/L) remaining after 12 weeks of rosuvastatin 10, 20, or 40 mg monotherapy, hsCRP was reduced by ~36% after switching to rosuvastatin 20 mg and fenofibric acid 135 mg for up to 52 weeks, and ~36% of patients shifted from hsCRP >=2 mg/L to <2 mg/L. CONCLUSIONS: Combination therapy with rosuvastatin and fenofibric acid may be effective for improving the inflammatory biomarker, hsCRP as well as other lipid abnormalities in patients with mixed dyslipidemia and high hsCRP. PMID- 21981844 TI - A novel mutation of apolipoprotein B in a French Canadian family with homozygous hypobetalipoproteinemia. PMID- 21981843 TI - Low-density lipoprotein particle number predicts coronary artery calcification in asymptomatic adults at intermediate risk of cardiovascular disease. AB - BACKGROUND: Clinicians require more discriminating measures of cardiovascular risk than those currently used in most clinical settings. A promising avenue of research concerns the relationship of low-density lipoprotein (LDL) subfractions to subclinical atherosclerosis. OBJECTIVE: To assess cross-sectional associations between subfractions of LDL cholesterol and coronary artery calcification (CAC). METHODS: The study sample comprised 284 asymptomatic clinic patients who were at intermediate risk of cardiovascular disease, aged 40-69 years, who were not taking a statin or niacin. Lipoprotein subclass measures were obtained by the use of proton nuclear magnetic resonance spectroscopy. CAC was assessed with computed tomography angiography (CTA). The analyses modeled the presence or absence of CAC. RESULTS: Total LDL particle number (LDL-P) had a stronger association with CAC than the traditional lipoprotein measures. Patients in the highest tercile of total LDL-P (1935-3560 nmol/L) were 3.7 times more likely to exhibit coronary artery calcification as those in the lowest tercile (620-1530 nmol/L). The independent effects of small LDL-P remained significant after adjustment for LDL cholesterol, high-density lipoprotein (HDL), triglycerides, non-HDL, and large LDL-P. HDL and non-HDL were not significant, independent predictors of CAC. CONCLUSION: Small LDL-P was a strong, independent predictor of the presence of CAC. Large prospective studies are needed to examine the effect of LDL particle number and size on coronary artery calcification. PMID- 21981845 TI - [Epidemiology of war injuries, about two conflicts: Iraq and Afghanistan]. AB - Since March 2003, military operations in Iraq "Operation Iraqi Freedom" (OIF) and in Afghanistan "Operation Enduring Freedom" (OEF), have made many wounded and killed in action (KIA). This article proposes to highlight the specific epidemiology of combat casualties, met in these both non-conventional and asymmetric conflicts. Personal protective equipments, Kevlar helmet and body armor, proved their efficiency in changing features of war injuries. Health Force Services organized trauma care system in different levels, with three main objectives: immediate basic medical care in battalion aid station, forward surgery and early aeromedical evacuation. The Joint Theater Trauma Registry (JTTR), a war injury registry, provides medical data, analyzed from the combat theater to the military hospital in United States. This analysis concluded that during modern conflicts, most injuries are caused by explosive devices; injuries are more severe and interestingly more specifically the head region and extremities than the trunk. Hemorrhage is the first cause of death, leading to the concept of avoidable death. Specific databases focused on mechanisms and severity of injuries, diagnostic and treatment difficulties, outcomes can guide research programs to improve war injuries prevention and treatment. PMID- 21981846 TI - [Proton pump inhibitors: impact of professional practice evaluation on prescriptions pertinence]. AB - OBJECTIVE: To improve the quality of proton pump inhibitors (PPI) prescription in an orthopaedic department. STUDY DESIGN: Prospective professional practice evaluation study. PATIENTS AND METHODS: A specific protocol concerning the best practice for using PPI in the perioperative period was established by anaesthesiologists and validated by all prescribers, according to recent recommendations published by French Afssaps. PPI prescription pertinence, mainly using the oral route, was based upon the presence of clearly identified risk factors. PPI mensual consumption and severe gastric complications were analyzed and compared with those obtained from the previous year. Ten months after the beginning of the protocol, the pertinence of PPI prescription was analyzed in 20 randomly selected medical records. Data are expressed in defined daily dose (DDD). RESULTS: After one year, a 35.5% decrease in oral PPI consumption was noted (901 +/- 211 before vs 581 +/- 235 DDD, after, P<0.05). A similar trend to a decrease in intravenous PPI consumption was observed (40 +/- 23 vs 22 +/- 26, P=0.06). During the same period, the overall incidence of severe gastric complication remained stable. The PPI prescription was pertinent in 85% of selected medical records. CONCLUSION: This study confirmed the interest of professional practice evaluation protocols to improve PPI prescription. A strong implication of all medical staff members is mandatory to maintain such benefits over time. PMID- 21981847 TI - Ruptured splenic artery pseudoaneurysm complicating acute pancreatitis. PMID- 21981848 TI - [Intraventricular colistin use in neonatal meningitis caused by Acinetobacter baumanii]. PMID- 21981849 TI - [Respiratory distress revealed a DRESS syndrome]. PMID- 21981850 TI - [Burnout in French doctors: a comparative study among anaesthesiologists and other specialists in French hospitals (SESMAT study)]. AB - OBJECTIVE: Burnout is one of the main chronic health problems with negative consequences on health care givers but also on quality of care. The main goal of Physician Health Survey was to study the frequency of burnout among salaried physicians and pharmacists and to compare anesthesiologists and intensivists (AI) with other practitioners (OP). The secondary end points were to analyze risk factors of burnout in each group. MATERIAL AND METHODS: An anonymous, self administered questionnaire was diffused via a specific website. Burnout was measured using the Copenhagen Burnout Inventory (CBI). Several different factors were examined: work/family conflict, salary satisfaction, quality of teamwork, interpersonal relationships, workplace influence, workload and perceived health. The role of each factor was calculated by multivariate logistic regression and comparisons were made between AI and OP. RESULTS: Among the 3196 responses, CBI revealed an elevated score of burnout in 38.4% in AI and in 42.4% in OP. In each group, a great gap was displayed between the CBI results and the self-assessment of burnout (15%). Among AI, risk factors of burnout were high quantitative demand (ORadj=3.40; CI(95) 1,34-8,63), Work/family conflict (ORadj=; 3.12 CI(95) 1.60 6.08), low quality of teamwork (ORadj=1.99; CI(95)1.14-3.47) and tense Relation within team (ORadj=1.92; CI(95) 1.25-2.95). All these factors are observed also among OP. Female gender, young age and dissatisfaction with pay have significant influence but different in the two groups. Claims of recurrent harassment by superiors is a risk factor for burnout only for the AP (adj.OR=1.83; CI(95) 1.04 3.22). DISCUSSION: Burnout affected near one about two salaried physicians and pharmacists in France. AI were not more concerned by burnout than OP but all of whom have difficulty identifying their own levels of psychological stress and burnout. Decreasing the level of different risk factors i.e. by improving the quality of teamwork should lead to reduce burnout frequency. PMID- 21981851 TI - [A fatal acute poisoning with glyphosate: importance of gastrointestinal toxicity]. PMID- 21981852 TI - [Prophylactic anti-emetic strategy: prevention among obstetrician-gynaecologists anaesthesia]. AB - OBJECTIVES: A prophylactic anti-emetic strategy should depend on the number of nausea and vomiting risk factors. This study was undertaken to evaluate the practices of postoperative nausea and vomiting (PONV) prevention practices among obstetrician-gynaecologists, anaesthetists. STUDY DESIGN: A prospective, self administered questionnaire survey was emailed to all Club d'Anesthesie Reanimation Obstetricale (Caro) members (French Obstetric and Gynaecology Anaesthetists' Association). METHODS: The questionnaire had closed-ended questions to evaluate each Caro member's prophylactic anti-emetic practices. Questions concerned demographic datas, prophylactic anti-emetic drugs administered to the patients with or without well known risk factors for developing PONV, the existence of protocol to prevent PONV in their own department of anaesthesiology and their awareness of the existence of French Society of Anaesthesia and Intensive Care (Sfar) PONV prevention guidelines 2007. RESULTS: Of 115 questionnaires, 66 respondents (57%) returned the questionnaires. Most of the respondents (74%) worked in a university hospital. Forty-two percent practiced exclusively in obstetric-gynaecology department. Fifty-six percent were anaesthetists for more than 20 years. Eighty-five percent of the physicians were well-informed about the SFAR's PONV prevention guidelines. Thirty seven percent of respondents assessed Apfel score systematically for all their patients. The percentages, which didn't calculate the probability of PONV with Apfel score or calculated only in cases of PONV history or travel sickness were 18% and 45% respectively. In cases of two or more risk factors, 63% used droperidol, dexamethasone and ondansetron in double or triple combinations. CONCLUSIONS: Although most surveyed practitioners were well informed about the new guidelines concerning PONV prevention, 27% not follow these guidelines regarding the administration of anti-emetic drugs. The calculation of Apfel score in the preoperative period must be also strengthened. PMID- 21981853 TI - Noninvasive transorbital alternating current stimulation improves subjective visual functioning and vision-related quality of life in optic neuropathy. AB - BACKGROUND: Noninvasive repetitive transorbital alternating current stimulation (rtACS) can improve visual field size in patients with optic nerve damage, but it is not known if this is of subjective relevance. We now assessed patient reported outcomes to determine the association between visual field changes and vision related quality of life (QoL). METHODS: Patients having visual field impairments long after optic nerve damage (mean lesion age 5.5 years) were randomly assigned to a rtACS (n = 24) or sham stimulation group (n = 18). Visual fields and patient reported outcome measures (vision-related QoL: National Eye Institute Visual Function Questionnaire, NEI-VFQ and health-related QoL: Short Form Health Survey, SF-36) were collected before and after a 10-day treatment course with daily sessions of 20 to 40 minutes. The primary outcome measure was the percent change from baseline of detection ability (DA) in defective visual field sectors as defined by computer-based high resolution perimetry (HRP). Secondary outcome parameters included further HRP parameters as well as static and kinetic perimetry results. Changes in QoL measures were correlated with changes in primary and secondary outcome measures in both groups. RESULTS: DA increase in the defective visual field was significantly larger after rtACS (41.1 +/- 78.9%, M +/- SD) than after sham stimulation (13.6 +/- 26.3%), P < 0.05. While there was a significant increase of DA in the whole tested HRP visual field after rtACS (26.8 +/- 76.7%, P < 0.05), DA in sham-stimulation patients remained largely unchanged (2.7 +/- 20.2%, ns). Results of secondary outcome measures (static and kinetic perimetry) provided further evidence of rtACS efficacy. Improvements in NEI-VFQ subscale "general vision" were observed in both groups but were larger in the rtACS group (11.3 +/- 13.5, Z = -3.21, P < 0.001) than in the sham group (4.2 +/- 9.4, Z = -1.73, P < 0.05) with a significant difference between groups (Z = 1.71, P < 0.05). DA change and some NEI-VFQ domains were correlated (r = 0.29, P < 0.05), but no significant correlations were observed between DA and SF-36 results. CONCLUSIONS: rtACS facilitates vision restoration after unilateral, long term optic nerve lesion as assessed both by objective DA changes and improvements in some NEI-VFQ subscales. Both were positively but low correlated, which suggests that factors other than visual field size also contribute to improved vision-related QoL. PMID- 21981854 TI - Restoration of vision after optic nerve lesions with noninvasive transorbital alternating current stimulation: a clinical observational study. AB - BACKGROUND: Non-invasive current stimulation can induce neuroplastic changes in the normal brain, including visual system structures. Because it is not known if such plasticity is of clinical value, we wished to learn if vision restoration can be induced after optic nerve damage. METHODS: In an open-label, clinical observational study 446 patients with optic nerve lesions were treated with non invasive repetitive transorbital alternating current stimulation (rtACS). Current bursts (<1000 MUA, 5-20 Hz) were applied to induce phosphenes for one or two 10 day stimulation periods. Efficacy was assessed by monocular measurements of visual acuity and visual field (VF) size. EEG recordings at rest (n = 68) were made before and after treatment and global power spectra changes were analyzed. RESULTS: rtACS improved VF size in the right and left eye by 7.1% and 9.3% (p < 0.001), respectively. VF enlargements were present in 40.4% of right and 49.5% of left eyes. Visual acuity (VA) significantly increased in both eyes (right = 0.02, left = 0.015; p < 0.001). A second 10-day course was conducted 6 months in a subset of 62 patients and resulted in additional significant improvements of VA. Analysis of EEG power spectra revealed that VA and VF improvements were associated with increased alpha power. Increased theta power was observed in patients that had only VF enlargements but no VA change. In contrast, non responders had increased delta power spectra in frontal and occipital areas. CONCLUSIONS: rtACS leads to long-lasting improvements in VA and VF size and after effects in EEG power spectra. Because physiological and clinical parameters are correlated we hypothesize that rtACS enhances plasticity by inducing synchronization in different cortical regions, but the precise mechanisms needs further clarification. These encouraging results require confirmation by controlled clinical trials. PMID- 21981855 TI - Symptoms induced by environmental irritants and health-related quality of life in patients with chronic cough - A cross-sectional study. AB - BACKGROUND: Chronic cough is a common condition, but some patients have no evident medical explanation for their symptoms. A group of patients has been identified, characterized by upper and lower airway symptoms triggered by chemicals and scents, and heightened cough sensitivity to inhaled capsaicin. Chronic cough is usually a prominent symptom in these patients, and it has been suggested that they suffer from sensory hyperreactivity.Our main aim was to analyse, in a group of patients with chronic cough, the presence of symptoms induced by environmental factors such as chemicals, scents, and cold air, and to measure the social and emotional influences of these symptoms in relation to quality of life. A second aim was to pilot-test a Swedish translation of a cough specific questionnaire. METHODS: A total of 119 patients with chronic cough were asked to answer three different questionnaires: a local symptom questionnaire, the Chemical Sensitivity Scale for Sensory Hyperreactivity (CSS-SHR), and the Nottingham Health Profile (NHP). In addition, a Swedish version of the Hull Airway Reflux Questionnaire (HARQ) was developed and answered by a subgroup of patients and healthy controls. RESULTS: Sixty-two patients (52%) with mean cough duration of 10.6 years answered the local symptom questionnaire, the CSS-SHR, and the NHP. Of these, 39 (63%) claimed to have cough and other symptoms induced by chemicals and scents. Compared to population-based findings, the patients scored higher on the CSS-SHR, and the CSS-SHR score was significantly higher among chemical-sensitive individuals (p < 0.001). The NHP showed that the patients had a significantly reduced quality of life, which was most pronounced among chemical sensitive individuals. The 31 patients who answered the HARQ had significantly higher scores (p < 0.0001) than 59 healthy controls. CONCLUSIONS: Among patients with chronic cough, a majority claimed that environmental factors induced coughing. Both the CSS-SHR and the HARQ score systems seem to be valuable instruments in the mapping of cough patients, supporting the novel paradigm of a cough hypersensitivity syndrome. Our results emphasize that cough is a substantial burden to the patient, influencing daily living and quality of life. PMID- 21981856 TI - Simple robust autotuning rules for 2-DoF PI controllers. AB - This paper addresses the problem of providing simple tuning rules for a Two Degree-of-Freedom (2-DoF) PI controller (PI(2)) with robustness considerations. The introduction of robustness as a matter of primary concern is by now well established among the control community. Among the different ways of introducing a robustness constraint into the design stage, the purpose of this paper is to use the maximum sensitivity value as the design parameter. In order to deal with the well known performance/robustness tradeoff, an analysis is conducted first that allows the determination of the lowest closed-loop time constant that guarantees a desired robustness. From that point, an analytical design is conducted for the assignment of the load-disturbance dynamics followed by the tuning of the set-point weight factor in order to match, as much as possible, the set-point-to-output dynamics according to a first-order-plus-dead-time dynamics. Simple tuning rules are generated by considering specific values for the maximum sensitivity value. These tuning rules, provide all the controller parameters parameterized in terms of the open-loop normalized dead-time allowing the user to select a high/medium/low robust closed-loop control system. The proposed autotuning expressions are therefore compared with other well known tuning rules also conceived by using the same robustness measure, showing that the proposed approach is able to guarantee the same robustness level and improve the system time performance. PMID- 21981857 TI - An opto-isolator based linearization technique of a typical thyristor driven pump. AB - A thyristor driven pump is operated by varying the DC input signal in the firing circuit of thyristor drive. This operation suffers from difficulties due to the nonlinear relation between thyristor output and DC input. In the present paper, an opto-isolator based linearization technique of a typical thyristor driven pump has been proposed. The design, fabrication and the necessary circuit diagram along with theoretical explanations of the resultant output has been described. The operation of the linearized thyristor driven pump has been studied experimentally and the experimental data before and after linearization are reported. The characteristic graphs are found to have very good linearity. PMID- 21981858 TI - Effect of the down-regulation of the high Grain Protein Content (GPC) genes on the wheat transcriptome during monocarpic senescence. AB - BACKGROUND: Increasing the nutrient concentration of wheat grains is important to ameliorate nutritional deficiencies in many parts of the world. Proteins and nutrients in the wheat grain are largely derived from the remobilization of degraded leaf molecules during monocarpic senescence. The down-regulation of the NAC transcription factor Grain Protein Content (GPC) in transgenic wheat plants delays senescence (>3 weeks) and reduces the concentration of protein, Zn and Fe in the grain (>30%), linking senescence and nutrient remobilization.Based on the early and rapid up-regulation of GPC in wheat flag leaves after anthesis, we hypothesized that this transcription factor is an early regulator of monocarpic senescence. To test this hypothesis, we used high-throughput mRNA-seq technologies to characterize the effect of the GPC down-regulation on the wheat flag-leaf transcriptome 12 days after anthesis. At this early stage of senescence GPC transcript levels are significantly lower in transgenic GPC-RNAi plants than in the wild type, but there are still no visible phenotypic differences between genotypes. RESULTS: We generated 1.4 million 454 reads from early senescing flag leaves (average ~350 nt) and assembled 1.2 million into 30,497 contigs that were used as a reference to map 145 million Illumina reads from three wild type and four GPC-RNAi plants. Following normalization and statistical testing, we identified a set of 691 genes differentially regulated by GPC (431 >= 2-fold change). Transcript level ratios between transgenic and wild type plants showed a high correlation (R = 0.83) between qRT-PCR and Illumina results, providing independent validation of the mRNA-seq approach. A set of differentially expressed genes were analyzed across an early senescence time-course. CONCLUSIONS: Monocarpic senescence is an active process characterized by large scale changes in gene expression which begins considerably before the appearance of visual symptoms of senescence. The mRNA-seq approach used here was able to detect small differences in transcript levels during the early stages of senescence. This resulted in an extensive list of GPC-regulated genes, which includes transporters, hormone regulated genes, and transcription factors. These GPC-regulated genes, particularly those up-regulated during senescence, provide valuable entry points to dissect the early stages of monocarpic senescence and nutrient remobilization in wheat. PMID- 21981859 TI - Low appendicular muscle mass is correlated with femoral neck bone mineral density loss in postmenopausal women. AB - BACKGROUND: After menopause, rapid bone mass loss occurs in response to hypoestrogenism. Several studies suggest that muscle mass and bone mineral density (BMD) are positively associated in postmenopausal women. Therefore, it may be assumed that postmenopausal low appendicular muscle mass (aMM) can increase BMD loss in a short period of time. OBJECTIVE: The purpose of this study was to assess relationship of aMM with femoral neck BMD in postmenopausal women. METHODS: Prospective, controlled clinical Trial including 64 women aged 45-70 years, who had not had their last menstruation for at least one year. Subjects were divided into two groups: low aMM (n = 32), and normal aMM (n-32). Femoral neck BMD and muscle mass were measured by DXA at baseline and after twelve months. Pairwise and independent t tests were used for data analysis. RESULTS: Baseline weight, BMI and muscle mass (total and appendicular) significantly differ between groups (p < 0.05). After twelve months, femoral neck BMD was significantly lower in the group with low aMM, whereas no significant difference was observed in the group with normal aMM (p < 0.05). CONCLUSION: In postmenopausal women, low appendicular muscle mass is associated negatively with femoral neck BMD in a short period of time. PMID- 21981861 TI - Visceral leishmaniasis in 26 HIV-negative adults. AB - BACKGROUND: Visceral leishmaniasis is a notifiable parasitic disease that had increased in incidence in our region on the past few years. It is common in children. In adults, it occurs more on a background of immunodeficiency, and frequently with incomplete clinical manifestations, making the diagnosis complicated. FINDINGS: The aim of our study is to reveal different features of visceral leishmaniasis in adults, through the analysis of its epidemiological, clinical and biological parameters, in a group of 26 patients. No one was infected with HIV or under immunosuppressive therapy Clinical presentation was generally conservative, but there was few differences in adults compared to children, concerning both the clinical symptoms and the laboratory parameters. Diagnosis was provided by direct examination of bone marrow smears in 24 cases (sensitivity 92%), and anti-leishmanial serology in the others. CONCLUSION: We should think to the diagnosis of VL even if the patient is not known immunocompromised, and even if the clinical is incomplete, to avoid a delay of care which can lead to serious complications. PMID- 21981862 TI - Pelvic dimorphism in relation to body size and body size dimorphism in humans. AB - Many mammalian species display sexual dimorphism in the pelvis, where females possess larger dimensions of the obstetric (pelvic) canal than males. This is contrary to the general pattern of body size dimorphism, where males are larger than females. Pelvic dimorphism is often attributed to selection relating to parturition, or as a developmental consequence of secondary sexual differentiation (different allometric growth trajectories of each sex). Among anthropoid primates, species with higher body size dimorphism have higher pelvic dimorphism (in converse directions), which is consistent with an explanation of differential growth trajectories for pelvic dimorphism. This study investigates whether the pattern holds intraspecifically in humans by asking: Do human populations with high body size dimorphism also display high pelvic dimorphism? Previous research demonstrated that in some small-bodied populations, relative pelvic canal size can be larger than in large-bodied populations, while others have suggested that larger-bodied human populations display greater body size dimorphism. Eleven human skeletal samples (total N: male = 229, female = 208) were utilized, representing a range of body sizes and geographical regions. Skeletal measurements of the pelvis and femur were collected and indices of sexual dimorphism for the pelvis and femur were calculated for each sample [ln(M/F)]. Linear regression was used to examine the relationships between indices of pelvic and femoral size dimorphism, and between pelvic dimorphism and female femoral size. Contrary to expectations, the results suggest that pelvic dimorphism in humans is generally not correlated with body size dimorphism or female body size. These results indicate that divergent patterns of dimorphism exist for the pelvis and body size in humans. Implications for the evaluation of the evolution of pelvic dimorphism and rotational childbirth in Homo are considered. PMID- 21981863 TI - [Role of laparoscopic surgery in the treatment of achalasia: an analysis of 50 cases]. AB - Achalasia is an uncommon oesophageal motor disorder, with a controversial therapeutic management. AIM: The aim of our study was to analyse our experience in the management of achalasia, assessing the impact of minimally invasive surgery, its complications and its outcomes in the short and medium term. METHODS: A retrospective and descriptive study was designed, including all patients operated on between 1999 and 2010 with the diagnosis of achalasia. Previous diagnostic tests, duration of symptoms, previous non-surgical treatment, surgical approach, associated antireflux intervention, surgical time and perioperative complications were analysed. RESULTS: A total of 50 patients, 24 males and 26 females, with a mean age of 47 years underwent laparoscopic surgery. The mean duration of the disease was 2 years. Eleven (22%) patients had received endoscopic treatment (1-4 sessions) prior to the surgery, with 100% of symptomatic recurrence. The surgery was accompanied by a Dor fundoplication in 48 patients, and Toupet fundoplication in the remaining two. The mean surgical time was 123 minutes. There were 9 intraoperative complications (5 gastric mucosal perforations, 2 bleeding, 1 liver injury and 1 aspiration); 4 postoperative complications (3 scapular pain and 1 sub-phrenic collection) were reported. The long-term subjective symptomatic response was excellent/good in 84% of patients, intermediate in 12% and a poor response in 4%. The mean follow-up was 28 months. CONCLUSIONS: Heller cardiomyotomy should be the treatment of choice in selected Achalasia patients, because of its short and long term outcomes, and its low morbidity. PMID- 21981864 TI - Adult neurogenesis and acupuncture stimulation at ST36. AB - Although it was believed that the brain was incapable of regeneration after embryonic development, neurogenesis is now known to occur into adulthood. Adult neurogenesis has been demonstrated in the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus of the hippocampus. Acupuncture has long been used to treat neurologic conditions, and recent reports suggest that neurogenesis may account for its beneficial effects. ST36 was the most often used acupoint in previous reports and was shown to enhance cell proliferation and neuronal differentiation. This acupoint may be linked to the brain through the primo vascular system, an anatomic structure thought to correspond to acupuncture meridians. This primitive vascular-like system appears to be involved in physiologic and pathologic processes by circulating substances throughout the body. The role of the primo vascular system as the link between the skin and brain underlying the beneficial effects of acupuncture requires further investigation. PMID- 21981865 TI - Primo vascular system of murine melanoma and heterogeneity of tissue oxygenation of the melanoma. AB - Murine melanoma requires the complex development of lymphatic, vascular, and non vascular structures. A possible relationship between the primo vascular system (PVS) and the melanoma metastasis has been proposed. In particular, the PVS may be involved in oxygen transport. Vasculogenic-like networks, similar to the PVS, have been found within melanoma tumors, but their functional relationship with the PVS and meridian structures are unclear. Herein, we report on the use of an electrochemical O(2) sensor to study oxygenation levels of melanoma tumors in mice. We consistently found higher tissue oxygenation in specific sites of tumors (n=5). These sites were strongly associated with vascular structures or the PVS. Furthermore, the PVS on the tumor surface was associated with adipose tissue. Our findings suggest that the PVS is involved in the regulation of metastasis. PMID- 21981866 TI - Violet laser acupuncture--part 3: pilot study of potential effects on temperature distribution. AB - Infrared thermography for temperature distribution monitoring was performed in ten healthy volunteers (M/F, 5/5; mean age +/- SD, 24.9 +/- 3.3 years) before, during, and after stimulation by noninvasive violet (405 nm) laser needle at the Dazhui (GV14) acupoint. Significant (p<0.001) increases of temperature at a region of interest around the acupoint were observed. Furthermore, temperature also increased significantly (p<0.05) at a so-called "far field" area Zhiyang (GV9). In two persons, however, needle acupuncture and placebo (deactivated laser) did not have the same temperature effects. Violet laser induces changes in skin surface temperature distributions. PMID- 21981867 TI - Violet laser acupuncture--part 4: acute effects on human arterial stiffness and wave reflection. AB - We investigated the effects of violet laser acupuncture on arterial stiffness and other important parameters of the functional state of the heart such as augmentation index (AIx). This investigation ties together the medical perspectives of Eastern and Western medical practitioners; the Western medical perspective of the functional states of the human heart including systolic and diastolic blood pressures, and the Eastern medical perspective regarding taking patients' pulses for diagnosis and using acupuncture for subsequent treatments. Pulse wave velocity (PWV) is a direct marker of arterial stiffness; AIx indicates wave reflection. Both parameters can be measured by cuff applied to the brachial artery. The first results from a pilot study of 10 healthy volunteers (M/F, 3/7; mean age +/- SD, 27.8 +/- 6.8 years) regarding violet laser acupuncture (405 nm; 110 mW; 500 MUm; 10 min) showed a marked but not statistically significant decrease in aortic PWV and an increase in brachial AIx during and after laser acupuncture at the acupoint Baihui. Further studies including control measurements are necessary. PMID- 21981868 TI - Synthesis of fuzzy logic for prediction and medical diagnostics by energy characteristics of acupuncture points. AB - A great number of reflexologies use ancient concepts that do not coincide with modern medical terminology of anatomy, physiology, and biophysics, substantially reducing the trust of today's physicians in this direction of their profession. Recently, several mathematical models of internal and biological active points of meridian structures interaction have been proposed. These models allowed specification of diseases for which reflex diagnostics and reflex therapy methods are most effective and also increased the efficacy of these procedures. Good results for the prediction and early diagnosis of diseases from the reaction energy of biologically active points (acupuncture points) are obtained using fuzzy logic decision making. PMID- 21981869 TI - Combined therapy using acupressure therapy, hypnotherapy, and transcendental meditation versus placebo in type 2 diabetes. AB - Type 2 diabetes is one of the most widespread diseases in the world. The main aim of this research was to evaluate the effect of combined therapy using acupressure therapy, hypnotherapy, and transcendental meditation (TM) on the blood sugar (BS) level in comparison with placebo in type 2 diabetic patients. We used "convenience sampling" for selection of patients with type 2 diabetes; 20 patients were recruited. For collection of data, we used an identical quasi experimental design called "nonequivalent control group." Therapy sessions each lasting 60-90 min were carried out on 10 successive days. We prescribed 2 capsules (containing 3g of wheat flour each) for each member of the placebo group (one for evening and one for morning). Pre-tests, post-tests, and follow-up tests were conducted in a medical laboratory recognized by the Ministry of Health and Medical Education of Iran. Mean BS level in the post-tests and follow-up tests for the experimental group was reduced significantly in comparison with the pre tests whereas in the placebo group no changes were observed. Combined therapy including acupressure therapy, hypnotherapy, and TM reduced BS of type 2 diabetic patients and was more effective than placebo therapy on this parameter. PMID- 21981870 TI - Comparison of acupuncturing Hegu (LI4) by metal or laser needle on facial blood perfusion using laser speckle technique. AB - AIM: To compare the difference of remote effects of acupuncture between metal needle and laser needle on facial blood perfusion (FBP). METHODS: Hand acupuncture and laser-needle acupuncture were randomly used on Hegu (LI4) in 20 healthy volunteers. FBP was observed by speckle contrast imager before, during, and after the acupunctures. RESULTS: For hand acupuncture there were gradual increases on the nose and left and right visor areas (p<0.05 or p<0.01) during the acupuncture and on an immediate increase (p<0.01) that remained constant during the acupuncture on the forehead area but no significant increase on mouth area. During laser-needle acupuncture, on the other hand, there was a tendency of increase on the nose, left visor, and right visor areas but these were non significant. CONCLUSION: Hand acupuncture can influence FBP in remote places connected by meridians. PMID- 21981871 TI - Protective effects of aqueous and ethanolic extracts of Portulaca oleracea L. aerial parts on H2O2-induced DNA damage in lymphocytes by comet assay. AB - The comet assay is a standard method for measuring DNA damage. In this study, the protective effects of ethanolic and aqueous extracts of Portulaca oleracea L. (P. oleracea) on human lymphocyte DNA lesions were evaluated with the comet assay. Lymphocytes were isolated from blood samples taken from healthy volunteers. Human lymphocytes were incubated in H(2)O(2) (50,100, and 200 MUM), aqueous extract (0.05, 0.1, 0.5, 1, and 2.5mg/ml), and ethanolic extracts (0.05, 0.1, 0.5, 1, and 2.5mg/ml) of P. oleraceae aerial parts alone with a combination of H(2)O(2) (100 MUM) with either 1 or 2.5mg/ml of both extracts at 4 degrees C for 30 minutes. The extent of DNA migration was measured using the alkaline single cell gel electrophoresis approach assay, and DNA damage was expressed as percentage tail DNA. We found that the aqueous extract of P. oleracea significantly inhibited DNA damage, while there was no effect of the ethanolic extract. These data suggest that the aqueous extract of P. oleracea can prevent oxidative DNA damage to human lymphocytes, which is likely due to antioxidant constituents in the extract. PMID- 21981872 TI - Study of the primo vascular system utilizing a melanoma tumor model in a green fluorescence protein expressing mouse. AB - A melanoma tumor is a representative malignant tumor. Melanoma tumor growth involves vigorous angiogenesis around the tumor and a vasculogenic-like network inside an aggressive tumor. Primo vessels (PVs) are also found on the surface of the tumor and coexist alongside blood vessels (BVs), and sometimes within the BVs. We hypothesized that the primo vessels system plays a significant role in regulating the development of a melanoma tumor, and therefore has a tight coupling with BVs and angiogenesis. To prove this hypothesis, we developed a murine melanoma model by inoculating melanoma cell lines into the abdominal region. We used a green fluorescent protein (GFP) expressing mouse as a host to distinguish the endogenous source of the tumor PVs. We found strong formation of PVs on the tumor that coexisted with BVs and expression of GFP. PVs also had a tight coupling with adipose tissues, especially with white adipose tissue. These data suggest that the PVs of an induced melanoma tumor evolve endogenously from the host body and may be highly related to BVs and adipose tissue. This model of PVs in an overexpressing GFP mouse is a useful system for observing PVs, primo nodes, and primo vessel networks, and has potential to be developed as a model for examining novel treatments for cancer metastasis. PMID- 21981873 TI - Radioisotope-antibody conjugates selectively target bone marrow prior to stem cell therapy. PMID- 21981874 TI - A method to adjust radiation dose-response relationships for clinical risk factors. AB - Several clinical risk factors for radiation induced toxicity have been identified in the literature. Here, we present a method to quantify the effect of clinical risk factors on radiation dose-response curves and apply the method to adjust the dose-response for radiation pneumonitis for patients with/without pre-existing pulmonary co-morbidities. PMID- 21981875 TI - Cranio-spinal irradiation with volumetric modulated arc therapy: a multi institutional treatment experience. PMID- 21981876 TI - Prophylactic irradiation of intervention sites in malignant pleural mesothelioma. AB - BACKGROUND AND PURPOSE: To assess the effectiveness of prophylactic irradiation of intervention track (PIT) to prevent tumor seeding in patients with malignant pleural mesothelioma. MATERIALS AND METHODS: A retrospective review was conducted of 171 patients with a histological diagnosis of pleural mesothelioma with some undergoing prophylactic irradiation of intervention sites. RESULTS: Forty-eight patients (28%) received PIT. A majority of patients were followed until death. Thoracoscopy (88%) was the procedure most often performed. Thirty-three percent of patients received chemotherapy. The median dose of PIT was 21 Gy in 3 fractions with electrons or 6 MV photons. The local progression free survival (LPFS) at the intervention site was significantly higher in the PIT group and was not influenced by chemotherapy. At 6 months, LPFS for the intervention sites was 91% with PIT and 74% without PIT (p=0.002). During the follow-up, 6 patients (13%) in the PIT group had tumor invasion of the subcutaneous tissue compared to 40 patients (33%) in the group without PIT (p=0.008). CONCLUSIONS: This study suggests that PIT in mesothelioma reduces the incidence of procedure tract metastasis. Finally, chemotherapy does not seem to have an influence on the incidence of tract metastasis. PMID- 21981877 TI - Concurrent doxorubicin and radiotherapy for anaplastic thyroid cancer: a critical re-evaluation including uniform pathologic review. AB - BACKGROUND AND PURPOSE: Anaplastic thyroid carcinoma (ATC) is a rare, aggressive malignancy. The potential for pathologic misclassification complicates interpretation of published data. One standard treatment option for locoregionally advanced disease is weekly low-dose doxorubicin with concurrent radiation therapy, and was previously developed at our institution. We evaluated our more recent experience with this approach, which included pathologic confirmation of all cases. MATERIALS AND METHODS: A retrospective review was performed on patients identified through the Memorial Sloan-Kettering Cancer Center (MSKCC) Cancer Database. INCLUSION CRITERIA: pathologically confirmed ATC; locoregional disease encompassable within a radiation portal; treatment with curative intent at MSKCC with planned weekly doxorubicin (10 mg/m(2)) and concurrent radiation. Principle outcomes assessed were locoregional progression free survival (LR-PFS) and overall survival (OS). RESULTS: Thirty-seven patients were included. Median radiotherapy dose was 57.6 Gy, and was >= 50Gy in 29 (78%), administered through hyperfractionated or once-daily schedules. One-year outcomes were LR-PFS, 45%; OS, 28%. CONCLUSION: The prognosis of patients with ATC remains grim and our current results appear inferior to those reported previously by our institution. More accurate histologic diagnoses and patient selection in the present series compared to the prior one may be responsible in part. Better therapy is desperately needed for this aggressive disease. PMID- 21981878 TI - Exhaled nitric oxide predicts radiation pneumonitis in esophageal and lung cancer patients receiving thoracic radiation. AB - BACKGROUND AND PURPOSE: Radiation pneumonitis is a significant toxicity following thoracic radiotherapy with no method to predict individual risk. MATERIALS AND METHODS: Sixty-five patients receiving thoracic radiation for lung or esophageal cancer were enrolled in a phase II study. Each patient received respiratory surveys and exhaled nitric oxide measurements before, on the last day of, and 30 60 days after completing radiotherapy (RT). Pneumonitis toxicity was scored using the common terminology criteria for adverse events, version 4.0. The demographics, dosimetric factors, and nitric oxide ratio (NOR) of end RT/pre-RT were evaluated for correlation with symptomatic patients (Grade >= 2). RESULTS: Fifty patients completed the trial. The pneumonitis toxicity score was: Grade 3 for 1 patient, Grade 2 for 6 patients, Grade 1 for 18 patients, and Grade 0 for 25 patients. Dosimetric factors were not predictive of symptoms. The NOR was 3.0 +/- 1.8 (range 1.47-6.73) for the symptomatic and 0.78 +/- 0.29 (range 0.33-1.37) for the asymptomatic patients (p=0.006). A threshold NOR of 1.4 separated symptomatic and asymptomatic patients (p<0.001). The average error was 4%. CONCLUSIONS: Elevation in eNO on the last day of radiotherapy predicted subsequent symptomatic radiation pneumonitis weeks to months after treatment. PMID- 21981879 TI - An evaluation of an automated 4D-CT contour propagation tool to define an internal gross tumour volume for lung cancer radiotherapy. AB - BACKGROUND AND PURPOSE: To evaluate an automated 4D-CT contouring propagation tool by its impact on the inter- and intra-physician variability in lung tumour delineation. MATERIALS AND METHODS: In a previous study, six radiation oncologists contoured the gross tumour volume (GTV) and nodes on 10 phases of the 4D-CT dataset of 10 lung cancer patients to examine the intra- and inter physician variability. In this study, a model-based deformable image registration algorithm was used to propagate the GTV and nodes on each phase of the same 4D-CT datasets. A blind review of the contours was performed by each physician and edited. Inter- and intra-physician variability for both the manual and automated methods was assessed by calculating the centroid motion of the GTV using the Pearson correlation coefficient and the variability in the internal gross tumour volume (IGTV) overlap using the Dice similarity coefficient (DSC). RESULTS: The time for manual delineation was (42.7+/-18.6)min versus (17.7+/-5.4)min when the propagation tool was used. A significant improvement in the mean Pearson correlation coefficient was also observed. There was a significant decrease in mean DSC in only 1 out of 10 primary IGTVs and 2 out of 10 nodal IGTVs. Intra physician variability was not significantly impacted (DSC>0.742). CONCLUSIONS: Automated 4D-CT propagation tools can significantly decrease the IGTV delineation time without significantly decreasing the inter- and intra-physician variability. PMID- 21981880 TI - [Tropical aortitis]. PMID- 21981881 TI - [Nephroprotection, fact or fiction?]. AB - Clinical studies of the last 15 years have shown the benefit of pharmacological interventions on the progression of chronic kidney disease, confirming the concept of nephroprotection. Pharmacological blockade of the renin angiotensin system remains the cornerstone of the nephroprotective treatment but the benefits and limitations are now better defined. The RAS blockers are all the more efficient than the proteinuria is abundant and nephroprotection is obtained in proportion to the reduction in proteinuria. Combinations of ACEI+ARA are not validated and their use should be considered only under the supervision of a specialist when optimal monotherapy has failed. The target blood pressure has been the subject of recent controversies, particularly in type 2 diabetic patients with nephropathy. The target should be individualized based on the main risk, renal or cardiovascular. Recent maneuvers have also shown a nephroprotective effect, including the correction of metabolic acidosis with sodium bicarbonate. PMID- 21981882 TI - [Benfluorex and valvular heart disease]. AB - Benfluorex is responsible of restrictive organic valvular regurgitations via one of its metabolites, the norfenfluramine. It has been withdrawn from the european market in June 2010. In France, about five millions of people have been exposed to benfluorex since its market launch in 1976. At the time of its market withdrawn, over 300,000 patients in France were taking the drug. Aortic and mitral valves are the most frequent involved. The prevalence of this type of valve damage is not yet known with accuracy. Severe regurgitations appear to be rare (less than one case per thousand exposed patients-year). PMID- 21981883 TI - [Are radars for recidivist delinquents on their way?]. PMID- 21981884 TI - [Influence of the social network on consumption in drug addicts exhibiting psychiatric comorbidity]. AB - This research used a qualitative methodology and was conducted on a sample of 22 participants with concomitant substance-related and mental health disorders. Today, dual diagnosis patients represent the standard rather than the exception. Our objectives were to consider the elements and processes of the social network to explain variations in consumption of alcohol and drugs. The social network refers to all bonds established by patients, mainly family, couple, friends and therapist relationships. The 22 patients have used a specialized addiction treatment in Montreal (Canada). A focused qualitative interview was conducted with each participant using an audionumeric recording. The analysis follows the method of the mixed approach of Miles and Huberman, which combines the objectives of the grounded theory and the ethnography. All the interviews were transcribed then coded and analyzed with QSR N' Vivo 2.0. The method uses an iterative process making a constant return between verbatim and codes. The qualitative analyses present patients' perceptions on the increases and reductions in alcohol and drug consumption. Family network refers to participants where the family is named as supporting a decrease in drug consumption: couple network refers to intimate relations supporting a decrease in consumption. Mutual help network refers to alcoholics anonymous (AA) or other self-help groups. Several verbatim have been included. We propose strategies for the substance abuse treatment centers based on: (1) the paradox influence of the social network and the importance of clinical evaluation of patients of social networks; (2) emotions management, especially negative feelings, which include training of feeling, recognizing and naming, ability to the express and communicate to others; (3) importance of groups of mutual aid providing periods of sharing, validating individual experiences and pushing away loneliness; (4) function of social support of the clinical professionals as substitute of an overdrawn network. PMID- 21981885 TI - [Comparative study of the subjective emotional experience among adolescents showing depressive symptoms associated or not with risk-taking behavior]. AB - INTRODUCTION: Relationships between risk-taking behavior and depressive disorders in young people are considered as a complex psychopathological problem. Previous findings showed strong correlations between substance abuse, risk-taking behavior and depressive symptoms. Nevertheless, questions remain concerning potential common factors of depression and risk-taking behavior. Besides research focusing on personality dimensions, some others highlight the role played by emotions and their pathological aspects. In these studies, pathological emotional processing such as alexithymia or specific deficit in emotional intensity was linked to both risk-taking behavior and depressive disorders. The aim of this study was to investigate potential specific emotional profiles of adolescents engaged in pathological risk-taking or depressive symptomatology, versus adolescents presenting an association of both. METHOD: Four hundred and eigty-eight adolescents (m(age)=14,93, SD=1,44), with 257 boys (m(age)=15, SD=1,51) and 231 girls (m(age)=14,52, SD=1,23), were spread into four groups: adolescents engaged in high level risk-taking, adolescents showing both high risk-taking and high depressive symptoms, depressed adolescents, and a control group without any pathological aspects. The four groups completed a set of three assessments: Youth Risk Behavior Surveillance Scale (YRBSS), Level of Emotional Awareness Scale (LEAS) and Differential Emotional Scale (DES). RESULTS: Adolescents engaged in risk-taking have the lowest level of emotional awareness and subjective emotional intensity, while adolescents of the second group (depression with risk-taking behavior) have a higher level on both measures. Depressed adolescents present the highest score of emotional awareness within the pathological groups, lower than controls. Paradoxically, their ability to represent themselves others' emotions were higher than the control group, just as the intensity of their subjective emotional experience in case of negative emotions. DISCUSSION: The results may be explained by a specific developmental hypothesis, in which emotional awareness growth from the early period of life to late childhood, allowing children to gradually experiment more and more complex subjective emotional experiences. However, early exposure to traumatic experiences or inadequate environment may lead to developmental arrests, in which emotional awareness is weak. In this case, a lack of emotional information caused by low emotional awareness may have pathological issues, in terms of depression and risk-taking behavior. Clinical implications of this interpretation are discussed. PMID- 21981886 TI - [Cannabis withdrawal syndrome in patients with cannabis dependence only, and in patients with cannabis and opioid dependence]. AB - BACKGROUND: The cannabis withdrawal syndrome occurs after cannabis cessation in more than 50% of dependent smokers. But although opioid-dependent patients are more frequently cannabis users and cannabis-dependent than the general population, the frequency and phenomenology of cannabis withdrawal symptoms in this specific population is unknown. Our hypothesis was that cannabis-dependent patients with current opioid dependence would experience the same withdrawal syndrome after cannabis cessation. OBJECTIVE: To describe cannabis withdrawal symptoms in cannabis-only dependent patients and in cannabis-dependent patients with current opioid dependence. METHODS: Using retrospective interviews, we evaluated the number and duration of six cannabis withdrawal symptoms in two groups: 56 cannabis-dependent patients without and 43 cannabis dependent patients with current opioid dependence. Cannabis and opioid dependence diagnoses were defined with DSM IV criteria using the MINI structured interview. RESULTS: The two groups were not different in terms of age of onset of cannabis use, and number of cannabis joints smoked at the time of the cannabis cessation attempt. The frequency of a cannabis withdrawal syndrome (defined as at least two different symptoms) did not differ in the two groups (65%). Neither was the proportion of subjects with the following symptoms: appetite or weight loss (30.8%), irritability (45.1%), anxiety (56%), aggression (36.3%) and restlessness (45.1%). Patients with cannabis dependence and current opioid dependence were more likely to report sleep disturbances (79.1 vs. 53.6%, chi(2)=6.91, P=0.007). The median duration of this cannabis withdrawal syndrome was 20 days post cessation. CONCLUSION: This is, to our knowledge, the first study describing cannabis withdrawal syndrome in cannabis-dependent patients with current opioid dependence. These patients experience a cannabis withdrawal syndrome as often as cannabis-only dependent subjects, but describe more frequently sleep disturbances. This high rate of sleep disturbances may cause relapse to cannabis use. PMID- 21981887 TI - [Confirmatory factor analysis of the short French version of the Center for Epidemiological Studies of Depression Scale (CES-D10) in adolescents]. AB - BACKGROUND: Screening depressivity among adolescents is a key public health priority. In order to measure the severity of depressive symptomatology, a four dimensional 20 items scale called "Center for Epidemiological Studies-Depression Scale" (CES-D) was developed. A shorter 10-item version was developed and validated (Andresen et al.). For this brief version, several authors supported a two-factor structure - Negative and Positive affect - but the relationship between the two reversed-worded items of the Positive affect factor could be better accounted for by correlated errors. OBJECTIVES: The aim of this study is triple: firstly to test a French version of the CES-D10 among adolescents; secondly to test the relevance of a one-dimensional structure by considering error correlation for Positive affect items; finally to examine the extent to which this structural model is invariant across gender. METHOD: The sample was composed of 269 French middle school adolescents (139 girls and 130 boys, mean age: 13.8, SD=0.65). Confirmatory Factorial Analyses (CFA) using the LISREL 8.52 were conducted in order to assess the adjustment to the data of three factor models: a one-factor model, a two-factor model (Positive and Negative affect) and a one-factor model with specification of correlated errors between the two reverse-worded items. Then, multigroup analysis was conducted to test the scale invariance for girls and boys. RESULTS: Internal consistency of the CES-D10 was satisfying for the adolescent sample (alpha=0.75). The best fitting model is the one-factor model with correlated errors between the two items of the previous Positive affect factor (chi(2)/dl=2.50; GFI=0.939; CFI=0.894; RMSEA=0.076). This model presented a better statistical fit to the data than the one-factor model without error correlation: chi(2)(diff) (1)=22.14, p<0.001. Then, the one-factor model with correlated errors was analyzed across separate samples of girls and boys. The model explains the data somewhat better for boys than for girls. The model's overall chi(2)(68) without equality constraints from the multigroup analysis was 107.98. The chi(2)(89) statistic for the model with equality constrained factor loadings was 121.31. The change in the overall Chi(2) is not statistically significant. This result implies that the model is, therefore, invariant across gender. The mean scores were higher for girls than boys: 9.69 versus 7.19; t(267)=4.13, p<0.001. CONCLUSIONS: To conclude, and waiting for further research using the French version of the CES-D10 for adolescents, it appears that this short scale is generally acceptable and can be a useful tool for both research and practice. The scale invariance across gender has been demonstrated but the invariance across age must be tested too. PMID- 21981888 TI - [Prevalence of pathological gambling in the general population around Paris: preliminary study]. AB - INTRODUCTION: Pathological gambling is characterized in the DSM IV-TR as one of the disorders of impulse control. Problem gambling is also part of what is considered as behavioural addictions, the criteria of which have been defined by Goodman, with intrusive thoughts about the game, spending more and more to play, unable to control, reduce or stop gambling despite negative consequences, etc. AIM OF THE STUDY: There is no epidemiological study in France on the prevalence of pathological gambling. We wanted to study the prevalence of pathological gambling in a sample of 529 persons: 368 gamblers of Pari Mutuel Urbain and La Francaise des Jeux, and 161 persons in the general population. The study took place between January 2008 and June 2009. METHODS: As instruments, we used: the South Oaks Gambling Scale (SOGS) for screening of pathological gambling and the BIS-10 for impulsiveness' evaluation, the HAD scale to assess anxiety and depression and the ASRS for the evaluation of attention deficit disorder/hyperactivity disorder (ADHD). RESULTS: The rate of pathological gambling in the general population is 1.24% (this result is similar to those found in other places, such as in Quebec). In the general population, the rate of play at risk is of 5.59%. Among the population of gamblers, the rate for pathological gambling (JP) amounted to 9.23% and risk gambling to 10.86%. Men are overrepresented in the group of pathological gamblers (88.9%), also with consumption of alcohol and tobacco. Suicide attempts are more important than in the general population, but the difference was statistically significant. Depression and anxiety are particularly high, 40% of gamblers with an anxiety score significantly higher. DISCUSSION: The results indicate rates close to those of other countries, such as Canada. It would be necessary to establish follow-up studies of populations and patients, as well as specific studies on people who frequent casinos, racetracks and internet gambling. The importance of the phenomenon is obvious, because almost 20% of players have a gambling problem or risk and these people do not consult despite their psychological problems, family, work, debts. PMID- 21981890 TI - [Influence between early maladaptive schemas and depression]. AB - INTRODUCTION: Early maladaptive schemas developed during childhood are relatively stable. Once activated, these early maladaptive schemas could influence reality perceptions and create cognitive distortions. Previous studies showed that early maladaptive schemas are linked to depression: early maladaptive schemas could be a risk factor for depression (Young, 2001) and a vulnerability marker for depression (Dozois, 2007). OBJECTIVES: The main objective of the present study was to explore the influence of early maladaptive schemas on depression severity among a French adult population. METHOD: One hundred and sixty-two participants (mean age 29 years; SD=13.86) were enrolled, 66 men (mean age 29 years; SD=13.65) and 106 women (mean age 30; SD=14.07). Participants were invited to complete the Young Schema Questionnaire, short version (YSQ-S1-Young 1994) and the Beck depression Inventory, 2nd version (BDI-II-Beck 1994). Fifty-six participants were randomly selected to complete a paper version of the scales, and 95 participants completed an online electronic version. RESULTS: Fifty-two percent of the participants were not depressed, 15% slightly depressed, 17% moderately depressed and 16% met criteria of severe depression. All 15 schemas scores were positively correlated to depression scores. Comparing schema scores and depression severity it can be noted that for severely depressed participants all schema scores were significantly higher, and six of 15 schemas were significantly higher in the case of moderate depression. In addition, three schemas (imperfection, vulnerability, fusional relation) are significantly and positively linked to depression scores, whereas one schema (everything is owed to me) appears to be a significantly negative predictor of associated depression. CONCLUSION: This study confirms results of previous research concerning the link between early maladaptive schemas and depression. What is more, the results show that the importance of these schemas increases with depression severity. The most important variation was found on schemas concerning interpersonal relationships like "abandonment" or "social insulation and social exclusion" as well as schemas related to personal competence as for example "failure" or "dependence and incompetence". Further research will be necessary to explore the role of depression as an activator or/and by reinforcing early maladaptive schemas. PMID- 21981889 TI - [Burnout and victimisation: impact of inmates' aggression towards prison guards]. AB - INTRODUCTION: Prison is typically considered as a dangerous setting partly because of promiscuity and violence, which leads to a whole series of suffering and frustration among prisoners. Due to their occupation, prison guards must ensure the safety of the inmates, their colleagues, as well as any other persons working in prison and in the prison setting. Thus, correctional guards are the "Bumper excitement" of prison violence and suffer from stressful and traumatic events. Indeed, inmates' sufferings and frustration are firstly expressed towards them because they share daily relationships with inmates. In addition, correctional guards are faced with the high inmate suicide risk. One potential consequence of these chronic stressful situations is burnout. Burnout is described as a three-dimensional syndrome composed of emotional exhaustion, depersonalization and sense of lack of personal accomplishment. Burnout is a severe psychological suffering, which can lead to depression. It has been initially identified among persons who are working with patients. Nevertheless, research shows that burnout is not a psychopathology of work but of the relationship with others. In other terms, burnout seems to arise when people share stressful, chronic and violent relationships with someone else. Burnout doesn't appear per se in any international classification of mental disorders: clinicians often use the diagnosis of adjustment disorder. PURPOSE: Our aim is to assess the impact of victimization on burnout among guards in French prisons. Prison guards were chosen for two major reasons. First, the custodial role of correctional officers is typically described as a stressful occupation, sensitive to burnout. Second, prison is generally considered "dangerous". Indeed, victimizations and aggressions frequently occur. Consequently, we hypothesize that burnout levels will be high for prison guards. We also hypothesize that the intensity of the victimizations (verbal, physical or armed aggression) will heighten burnout levels. MATERIAL AND METHODS: Two hundred and thirty-five prison guards were involved. Among these 235 correctional guards, there were 46 women and 188 men, ranging from 22 to 56 years old. Victimizations were very common: more than 87 % had experienced an aggression, whether verbally, physically or armed. They were asked to fill out the French form of the Maslach burnout Inventory (MBI). The MBI is a 22-item self-report measurement that assesses the three dimensions of burnout: emotional exhaustion, depersonalization and personal accomplishment. Items are rated on a 7-point scale ranging from 0 ("never") to 6 ("every day"). We have statistically created a new global level of burnout with the three dimensions. It is called "burnout level". We have assessed two sets of independent variables (VI): demographic VI (age, sex, tenure, level of studies) and correctional VI (penal status of prison, victimizations). Regarding our dependent variables, we have four levels which are (1) global burnout (GB), (2) emotional exhaustion (EE), (3) depersonalization (D), and (4) personal accomplishment (PA). For the purpose of our study, we carried out variance analyses (Anova) in order to compare the averages of our groups of subjects. Further to Anova, we chose the Bonferroni/Dunn post hoc test. RESULTS: The results indicate that demographic variables such as age, sex or level of studies have no significant effect on GB, EE, D and PA levels. Tenure has a significant effect on GB and D levels. Concerning correctional variables, results show that the penal status of prison has a significant effect on GB and EE. Prison guards working with inmates incarcerated for more than 5years report higher GB and EE than their counterparts working with inmates not already convicted. Victimizations have a significant effect on GB, EE, D and PA levels. Prison guards with physical or armed aggressions report higher global GB, EE, D and PA levels than prison guards without aggressions. Furthermore, prison guards with physical or armed aggressions report higher global GB and D levels than prison guards with verbal aggressions. Two major points are highlighted by our study. First, characteristics of prison and inmates are related to burnout among prison guards. Second, victimizations lead to burnout. PMID- 21981891 TI - [Validation study of the French schizotypal personality questionnaire in a sample of adolescents: a confirmatory factor analysis]. AB - AIMS: This article aims to validate the schizotypal personality questionnaire in a sample of French speaking adolescents. Because early schizotypal manifestations are predictive of psychosis-proneness, reliable self-report measures are crucial for early detection of vulnerability to schizophrenia during adolescence. Unlike most existing self-reports, the questionnaire de personnalite schizotypique (SPQ) assesses individual differences in all nine feature of DSM-IV schizotypal personality (i.e. ideas of reference, excessive social anxiety, odd beliefs, unusual perceptual experience, odd behaviour, no close friends, odd speech, constricted affect and suspiciousness). Furthermore, it yields dimensional scores concerning the main schizotypal factors, which represent valuable information for the clinician's case formulation and can be used as a screening instrument in the general population. METHOD: Our sample consisted of 174 adolescents (98 girls) between 12 and 17 years old. All completed the SPQ 74-item self-report. Participants were recruited in secondary schools in Switzerland, and through the child and adolescent community outpatient psychiatric service (office medico pedagogique) affiliated to the University of Geneva's Psychiatry Department and to the Canton of Geneva Education Department. A confirmatory factorial analysis was conducted on our sample to test nine competing models of SPQ. The 3-factor model of Raine et al. was compared to concurrent 2, 3, and 4-factor models. Simple structure models of Raine et al. and Stefanis et al. were also tested. RESULTS: The following observations were highlighted in our results: (1) goodness of-fit indices are better for structures allowing cross loadings than for simple structures; (2) amongst the simple structures, the best goodness-of-fit index was obtained for the Raine model and (3) the fit between our data and the Raine model is improved by a cross loading for suspiciousness subscale. The latter seems problematic for the global data fitting. This led us to test simple structures models of Siever and Gunderson, Raine et al., and Stefanis et al., based on eight subscales rather than nine. Without suspiciousness subscale, goodness-of-fit indices are enhanced in these three models. The 3-factor model yields the clearest and most reliable results in comparison with other competing models. In summary, the best goodness-of-fit indices were obtained for the 3-factor Raine model. Goodness-of-fit indices could be improved by the exclusion of the suspiciousness scale. CONCLUSIONS: Consistent with earlier analyses by Raine et al. and Dumas et al., our data confirm the 3-factor model of the SPQ (cognitive perceptive; interpersonal; disorganized) in a sample of French speaking adolescents. Our analyses confirm that two dimensions are insufficient to explain the structure of schizotypy during adolescence. These results further suggest the stability of a 3-factor structure during lifespan. We note that the inclusion of the suspiciousness subscales engenders statistical issues. Most studies to date have dealt with these issues by performing a cross-loading with this subscale, or by the inclusion of a paranoid factor which is linked with the negative and the cognitive-perceptive factors. We found that the most statistically sound strategy was reached without the inclusion of the suspiciousness subscale. Future studies with larger samples could investigate the SPQ structure at an item-level, which carries the benefit of reduced restrictions on the factorial analysis. In conclusion, the current study shows that the French version SPQ constitutes a reliable self-report questionnaire for the assessment of schizotypal trait expression during adolescence that may assist in the evaluation of psychosis proneness in youths. PMID- 21981892 TI - [Hyperhomocysteinemia and schizophrenia: case control study]. AB - OBJECTIVES: Homocysteine (Hcys) is a sulphur-containing amino acid that has been widely investigated for its putative role in neuropsychiatric disorders. Elevated plasma homocysteine levels have been associated with schizophrenia. Among other factors, low folate and vitamin B12 levels have been implicated in the increase in homocysteine. The aim of the study was to determine plasma Hcys, folate and vitamin B12, and the frequency and severity of hyperhomocysteinemia in patients with schizophrenia, and to investigate the association between Hcys and clinical features and its relationship with folate and vitamin B12 levels. METHODS: This was a case-control study carried out on 61 (54 males and seven females, mean age=33.3 +/- 9.2) inpatients with chronic schizophrenia according to DSM-IV criteria and 46 (25 males and 21 females, mean age=45.9 +/- 14.2) healthy controls. Most of patients (90.2%) were treated by first generation antipsychotics with a mean daily dosage of 401.6 mg chlorpromazine equivalents. Total homocysteine serum levels were determined quantitatively by fluorescence polarization immunoassay (FPIA) with an AxSYM analyzerTM (Abbott). Quantitative vitamin B12 and folate serum levels were measured with an Elecsys 2010 analyzerTM (Roche Diagnostics). Differences between patients and controls were examined using a two-way Ancova with gender and diagnosis as independent variables, adjusting for age. RESULTS: Patients with schizophrenia showed higher plasma Hycs and lower plasma folate than controls (mean=16.1 MUmol/L in patients versus 10.9 MUmol/L in controls; P=0.028 for Hycs and 4.2 MUg/L in patients versus 8.2 MUg/L in controls; P<0.001 for folate). Patients and controls did not differ in vitamin B12 levels. Both male and female patients had increased plasma Hcys compared to controls. Hyperhomocysteinemia (Hcys levels>15 MUmol/L) was present in 34.4% of the patients versus 15.2% in controls. The prevalence of moderate hyperhomocysteinemia (Hcys levels: 15-29 MUmo/L) was 26.2% and that of intermediate hyperhomocysteinemia (Hcys levels: 30-100 MUmol/L) was 8.2%. In patients with schizophrenia, plasma Hcys was not correlated with age (r=0.07; P=0.56), duration of illness (r=-0.04; P=0.78) and did not differ with gender and clinical sub-types. Moreover, plasma Hcys was higher in patients without family history of psychiatric disorders (19.2 MUmol/L) versus 12.7 MUmol/L in patients with family history of psychiatric disorders (P=0.032). Concerning therapeutic features, plasma Hcys did not differ with type of antipsychotic and was not related to daily dosage of antipsychotics. A negative correlation was found between plasma Hcys and vitamin B12 levels (r=-0.26; P=0.04). CONCLUSION: These results confirm an increase of Hcys levels in schizophrenic patients and suggest that it is associated with absence of family history of psychiatric disorders and with low vitamin B12 levels. Hyperhomocyteinemia could be related to the pathophysiology of aspects of this illness. Homocysteine should be considered as a factor to consider in monitoring and management of patients with schizophrenia. PMID- 21981893 TI - [Cognitive remediation program for individuals living with schizophrenia (Recos): preliminary results]. AB - BACKGROUND: Nowadays, cognitive remediation is widely accepted as an effective treatment for patients with schizophrenia. In French-speaking countries, techniques used in cognitive remediation for patients with schizophrenia have been applied from those used for patients with cerebral injury. As cognitive impairment is a core feature of schizophrenia, the Departement de psychiatrie du CHUV in Lausanne (DP-CHUV) intended to develop a cognitive remediation program for patients with a schizophrenia spectrum disease (Recos-Vianin, 2007). Numerous studies show that the specific cognitive deficits greatly differ from one patient to another. Consequently, Recos aims at providing individualized cognitive remediation therapy. In this feasibility trial, we measured the benefits of this individualized therapy for patients with schizophrenia. Before treatment, the patients were evaluated with a large battery of cognitive tests in order to determine which of the five specific training modules - Verbal memory, visuospatial memory and attention, working memory, selective attention, reasoning - could provide the best benefit depending on their deficit. OBJECTIVES: The study was designed to evaluate the benefits of the Recos program by comparing cognitive functioning before and after treatment. METHOD: Twenty-eight patients with schizophrenia spectrum disorders (schizophrenia [n=18], schizoaffective disorder [n=5], schizotypal disorder [n=4], schizophreniform disorder [n=1], DSM IV-TR) participated in between one and three of the cognitive modules. The choice of the training module was based on the results of the cognitive tests obtained during the first evaluation. The patients participated in 20 training sessions per module (one session per week). At the end of the training period, the cognitive functioning of each patient was reevaluated by using the same neuropsychological battery. RESULTS: The results showed a greater improvement in the cognitive functions, which were specifically trained, compared to the cognitive functions, which were not trained. However, an improvement was also observed in both types of cognitive functions, suggesting an indirect cognitive gain. CONCLUSION: In our view, the great heterogeneity of the observed cognitive deficits in schizophrenia necessitates a detailed neuropsychological investigation as well as an individualized cognitive remediation therapy. These preliminary results need to be confirmed with a more extended sample of patients. PMID- 21981894 TI - [Pathological gambling: risk factors]. AB - CONTEXT AND OBJECTIVE: In France, consumption of gambling games increased by 148% between 1960 and 2005. In 2004, gamblers lost approximately 0.9% of household income, compared to 0.4% in 1960. This represents approximately 134 Euros per year and per head. In spite of this important increase, the level remains lower than the European average (1%). However, gambling practices may continue to escalate in France in the next few years, particularly with the recent announce of the legalisation of online games and sports betting. With the spread of legalised gambling, pathological gambling rates may increase in France in the next years, in response to more widely available and more attractive gambling opportunities. In this context, there is a need for better understanding of the risk factors that are implicated in the development and maintenance of pathological gambling. METHODS: This paper briefly describes the major risk factors for pathological gambling by examining the recent published literature available during the first quarter of 2008. This documentary basis was collected by Inserm for the collective expert report procedure on Gambling (contexts and addictions). Seventy-two articles focusing on risk factors for pathological gambling were considered in this review. Only 47 of them were taken into account for analysis. The selection of these 47 publications was based on the guide on literature analysis established by the French National Agency for Accreditation and Assessment in Health (ANAES, 2000). Some publications from more recent literature have also been added, mostly about Internet gambling. RESULTS: We identify three major types of risk factors implicated in gambling problems: some of them are related to the subject (individual factors), others are related to the object of the addiction, here the gambling activity by itself (structural factors), and the last are related to environment (contextual or situational factors). Thus, the development and maintenance of pathological gambling seems to be conditioned by the interaction of a person and a gambling activity, in a particular context. This conceptual model is based on the well-known theory of Olivenstein on toxicomania, which was proposed in the seventies. The structural factors that appeared to be highly related to pathological gambling development and maintenance are payment modality, entertaining dimension, temporality, reward level, educational messages, gambling ambiance, gambling medium and part of hazard. Among contextual factors, availability and accessibility of gambling opportunities are well known. However, social and economic factors (e.g. culture, ethnicity, religion, education) are also important. Lastly, among individual factors, psychosocial factors are gender, age, familial and personal antecedents and psychiatric comorbidities. Neurobiological factors are not discussed here. CONCLUSIONS: This paper briefly summarises risk factors for development and maintenance of pathological gambling. It highlights that these factors are very similar to those that are implicated in substance use disorders, except for the gambling activity and context. Prevention regarding behavioural addictions should, in the future, take advantage of the findings on substance use disorder, since behavioural addictions are less known. Conversely, it seems obvious that findings on pathological gambling, and more widely behavioural addictions, could highlight all types of addiction. It appears that this fact is especially valid with regards to the evolution and stability of addictive status, which must be taken into account for treatment proposals. PMID- 21981895 TI - [Management, needs and expectations of patients suffering from bipolar I disorders (The ECHO study - France)]. AB - AIM: The ECHO study is the first French study directly asking patients with bipolar I disorders on the history and experiences of their disease, their perceptions of care, their sociofamilial relationships, and their expectations regarding what should be done by healthcare professionals and their environment. METHOD: Three hundred euthymic patients suffering from bipolar disorder I were interviewed using a semi-standardized evaluation through telephone interviews. These patients were selected according to the quota method of nationally representative INSEE 99 to be representative of the French population. RESULTS: Ninety-nine percent of patients consulted at least once for psychological signs before the correct diagnosis was established. The average age at the time of diagnosis was of 30.1 years (+/- 11.3). The average time between first consultation for psychological symptoms and diagnosis is about 5 years. In 92% of cases, the psychiatrist is the health professional that made the diagnosis; 74% of patients were also followed by a general practitioner. One hundred percent of participants had been hospitalized for manic episodes (criterion for inclusion in the study) and 86% were also hospitalized for depressive symptoms. The experience of hospitalization is positive (feeling of security for 84% of the sample, feelings of being helped for 81% of the sample), although these experiences are also associated with the perception of confinement (52% of the sample). At the time of the interview, 97% of these patients were followed by one or more health professionals. Only 34% of these patients were taking a mood stabilizer (lithium, anticonvulsant or atypical antipsychotic with indications in France for bipolar disorder), while 44% were taking an antidepressant and 38% were taking anxiolytics; 84% of patients had experienced side effects related to their current treatment. Acceptance of the disease is difficult and only 56% of patients personally feel they suffer from bipolar disorders. Patients believe that their mental health problems have a significant impact on their lives, including impact on their self-esteem and happiness. Relationships with family, friends but also sexual relations are affected. Even in the euthymic phase, 44% of patients have difficulties in their daily tasks. Three quarters of patients said they had already experienced rejection or discrimination related to their disease. Finally, patients gave a score of 6.4 out of 10 to assess the impact of the disorder on their quality of life. Patients request more dialogue with health professionals and a more personalized treatment, taking into account side effects. They also want more information on the treatment. They would also like to be supported, together with their families, and advised on how to cope with the disease. PMID- 21981896 TI - Transgenic Plasmodium parasites stably expressing Plasmodium vivax dihydrofolate reductase-thymidylate synthase as in vitro and in vivo models for antifolate screening. AB - BACKGROUND: Plasmodium vivax is the most prevalent cause of human malaria in tropical regions outside the African continent. The lack of a routine continuous in vitro culture of this parasite makes it difficult to develop specific drugs for this disease. To facilitate the development of anti-P. vivax drugs, bacterial and yeast surrogate models expressing the validated P. vivax target dihydrofolate reductase-thymidylate synthase (DHFR-TS) have been generated; however, they can only be used as primary screening models because of significant differences in enzyme expression level and in vivo drug metabolism between the surrogate models and P. vivax parasites. METHODS: Plasmodium falciparum and Plasmodium berghei parasites were transfected with DNA constructs bearing P. vivax dhfr-ts pyrimethamine sensitive (wild-type) and pyrimethamine resistant (mutant) alleles. Double crossover homologous recombination was used to replace the endogenous dhfr ts of P. falciparum and P. berghei parasites with P. vivax homologous genes. The integration of Pvdhfr-ts genes via allelic replacement was verified by Southern analysis and the transgenic parasites lines validated as models by standard drug screening assays. RESULTS: Transgenic P. falciparum and P. berghei lines stably expressing PvDHFR-TS replacing the endogenous parasite DHFR-TS were obtained. Anti-malarial drug screening assays showed that transgenic parasites expressing wild-type PvDHFR-TS were pyrimethamine-sensitive, whereas transgenic parasites expressing mutant PvDHFR-TS were pyrimethamine-resistant. The growth and sensitivity to other types of anti-malarial drugs in the transgenic parasites were otherwise indistinguishable from the parental parasites. CONCLUSION: With the permanent integration of Pvdhfr-ts gene in the genome, the transgenic Plasmodium lines expressing PvDHFR-TS are genetically stable and will be useful for screening anti-P. vivax compounds targeting PvDHFR-TS. A similar approach could be used to generate transgenic models specific for other targets of interest, thus facilitating the development of anti-P. vivax drugs in general. PMID- 21981897 TI - Clinical utility of routine pre-operative axillary ultrasound and fine needle aspiration cytology in patient selection for sentinel lymph node biopsy. AB - In patients with operable breast cancer, pre-operative evaluation of the axilla may be of use in the selection of appropriate axillary surgery. Pre-operative axillary ultrasound (US) and fine needle aspiration cytology (FNAC) assessments have become routine practice in many breast units, although the evidence base is still gathering. This study assessed the clinical utility of US+/-FNAC in patient selection for either axillary node clearance (ANC) or sentinel lymph node biopsy (SLNB) in patients undergoing surgery for operable breast cancer. Over a two-year period, 348 patients with a clinically negative axilla underwent axillary US. 67 patients with suspicious nodes on US also underwent FNAC. The sensitivity and specificity of axillary investigations to determine nodal involvement were 56% (confidence interval: 47-64%) and 90% (84-93%) for US alone, and 76% (61-87%) and 100% (65-100%) for FNAC combined with US, respectively. With a positive US, the post-test probability was 78%. A negative US carried a post-test probability of 25%. When FNAC was positive, the post-test probability was greater than unity. A negative FNAC yielded a post-test probability of 52%. All patients with positive FNAC and most patients with suspicious US were listed for axillary node clearance (ANC) after consideration at the multi-disciplinary team (MDT) meeting. With pre operative axillary US+/-FNAC, 20% of patients were saved a potential second axillary procedure, facilitating a reduction in the overall re-operation rate to 12%. In this study, a positive pre-operative US+/-FNAC directs patients towards ANC. When the result is negative, other clinico-pathological factors need to be taken into account in the selection of the appropriate axillary procedure. PMID- 21981898 TI - Cardiac response to exercise in normal-weight and obese, Hispanic men and women: implications for exercise prescription. AB - AIM: The effects of obesity on cardiac function during incremental exercise to peak oxygen consumption (VO(2peak)) have not been previously described. The purpose of this study was to compare submaximal and maximal cardiac function during exercise in normal-weight and obese adults. METHODS: Normal-weight (n = 20; means +/- SE: age = 21.9 +/- 0.5 years; BMI = 21.8 +/- 0.4 kg m(-2)) and obese (n = 15; means +/- SE: age = 25.1 +/- 5.2 years; BMI = 34.1 +/- 01.0 kg m( 2)) participants were assessed for body composition, VO(2peak) and cardiac variables (thoracic bioimpedance analysis) at rest and at heart rates (HR) of 110, 130, 150 and 170 beats min(-1) and maximal HR during incremental cycling exercise to exhaustion. Differences between groups were assessed with mixed-model ancova with repeated measures. Cardiac variables were statistically indexed for body surface area and resting HR. VO(2) and arteriovenous oxygen difference (a vO(2)) were statistically indexed for fat-free mass and resting HR. RESULTS: Significant main effects for group indicated obese participants had higher cardiac output (Q) index and stroke volume (SV) index but lower ejection fraction (EF) and a-vO(2) index during incremental exercise to exhaustion compared with their normal-weight peers, despite similar submaximal and maximal VO(2) and absolute power outputs (P < 0.05). CONCLUSIONS: Our findings suggest that although Q index and SV index were higher in obese, young adults, EF and a-vO(2) index were significantly lower when compared to matched, normal-weight adults. PMID- 21981900 TI - Lexical- and perceptual-based object effects in the two-rectangle cueing paradigm. AB - Previous studies demonstrate that attentional selection can be object-based, in which the object is defined in terms of Gestalt principles or lexical organizations. Here we investigate how attentional selection functions when the two types of objects are manipulated jointly. Experiment 1 replicated Li and Logan (2008) by showing that attentional shift between two Chinese characters is more efficient when they form a compound word than when they form a nonword. Experiment 2A presented characters either alone or within rectangles (Egly, Driver, & Rafal, 1994) and the characters in a rectangle formed either a word or a nonword. Experiment 2B differed from Experiment 2A in that the two characters forming a word were in different rectangles. Experiment 3A presented the two characters of a word either within a rectangle or in different rectangles. Experiment 3B used the same design as Experiment 3A but presented stimuli of different types in random orders, rather than in blocks as in Experiments 2A, 2B and 3A. In blocked presentation, detection responses to the target color on a character were faster when this character and the cue character formed a word than when they did not, and the size of this lexical-based object effect did not vary according to whether the two characters were presented alone or within or between rectangles. In random presentation, however, the lexical-based object effect was diminished when the two characters of a word were presented in different rectangles. Overall, these findings suggest that the processes that constrain attention deployment over conjoined objects can be strategically adjusted. PMID- 21981899 TI - [Spontaneous rupture of varicose veins in the third trimester of pregnancy: diagnosis achieved by MRI]. AB - This is a case report, for the first time in the literature, of a third trimester pregnant woman with acute abdominal pain for which the diagnosis of varicose veins rupture was achieved by MRI. PMID- 21981901 TI - Security of attachment and quality of mother-toddler social interaction in a high risk sample. AB - The quality of children's social interactions and their attachment security with a primary caregiver are two widely studied indices of socioemotional functioning in early childhood. Although both Bowlby and Ainsworth suggested that the parent child interactions underlying the development of attachment security could be distinguished from other aspects of parent-child interaction (e.g., play), relatively little empirical research has examined this proposition. The aim of the current study was to explore this issue by examining concurrent relations between toddler's attachment security in the Strange Situation Procedure and quality of mother-child social interaction in a high-risk sample of toddlers characterized by prenatal cocaine exposure and low levels of maternal education. Analyses of variance suggested limited relations between attachment security and quality of social interaction. Further research examining the interrelations among various components of the parent-child relationship is needed. PMID- 21981902 TI - [Emigrate or not? How would the next Spanish generation of physicians decide?]. PMID- 21981903 TI - [When should specific pharmacological treatment be stopped in Alzheimer's?]. PMID- 21981904 TI - Hepatotoxicity and liver enzyme alteration in patients with immunobullous diseases receiving immunosuppressive therapy. AB - To avoid complications of high dose corticosteroid, pemphigus patients are usually co-treated with other immunosuppressive agents. Liver enzyme abnormality occurs commonly during treatment and occasionally causes discontinuation of drugs. To assess the rate of therapy-induced hepatotoxicity in patients with immunobullous diseases, we conducted a study of 250 pemphigus patients under immunosuppressive therapy prospectively. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) plasma levels were recorded before the start of treatment and every week under treatment (up to 3 weeks). Hepatotoxicity was defined as the rise in the ALT plasma levels to greater than twice the upper normal limit. Approximately 81% of patients received prednisolone and azathioprine. Approximately 12% received only prednisolone. Hepatotoxicity occurred in 2.9% (n = 8) of patients after 1 week, in 7.8% (n = 20) after 2 weeks and in 11.5% (n = 29) after 3 weeks. No patient had jaundice or other clinical manifestations of hepatitis. The mean values of ALT and AST before the start of treatment were 20.7 +/- 13.7 and 17.6 +/- 10.8 U/L, respectively that grew to 47.5 +/- 28.5 and 26.8 +/- 14.5 U/L, 3 weeks after the initiation of treatment. Distribution of changes was not significantly different among groups of age, sex, immunosuppressive drugs and isoniazid consumption. Under usual treatment of pemphigus, hepatotoxicity occurs in 10% of patients during the first 3 weeks of therapy that does not seem to be associated with azathioprine or mycophenolate mofetil exclusively. High doses of prednisolone may play a role. PMID- 21981906 TI - Joint hypermobility in children with idiopathic scoliosis: SOSORT award 2011 winner. AB - BACKGROUND: Generalized joint hypermobility (JHM) refers to increased joint mobility with simultaneous absence of any other systemic disease. JHM involves proprioception impairment, increased frequency of pain within joints and tendency to injure soft tissues while performing physical activities. Children with idiopathic scoliosis (IS) often undergo intensive physiotherapy requiring good physical capacities. Further, some physiotherapy methods apply techniques that increase joint mobility and thus may be contraindicated.The aim of this paper was to assess JHM prevalence in children with idiopathic scoliosis and to analyze the relationship between JHM prevalence and the clinical and radiological parameters of scoliosis. The methods of assessment of generalized joint hypermobility were also described. MATERIALS AND METHODS: This case-control study included 70 subjects with IS, aged 9-18 years (mean 13.2 +/- 2.2), Cobb angle range 10 degrees -53 degrees (mean 24.3 +/- 11.7), 34 presenting single curve thoracic scoliosis and 36 double curve thoracic and lumbar scoliosis. The control group included 58 children and adolescents aged 9-18 years (mean 12.6 +/- 2.1) selected at random. The presence of JHM was determined using Beighton scale complemented with the questionnaire by Hakim and Grahame. The relationship between JHM and the following variables was evaluated: curve severity, axial rotation of the apical vertebra, number of curvatures (single versus double), number of vertebrae within the curvature (long versus short curves), treatment type (physiotherapy versus bracing) and age.Statistical analysis was performed with Statistica 8.1 (StatSoft, USA). The Kolmogorov-Smirnov test, U Mann-Whitney test, Chi2 test, Pearson and Spermann correlation rank were conducted. The value p = 0.05 was adopted as the level of significance. RESULTS: JHM was diagnosed in more than half of the subjects with idiopathic scoliosis (51.4%), whilst in the control group it was diagnosed in only 19% of cases (p = 0.00015). A significantly higher JHM prevalence was observed in both girls (p = 0.0054) and boys (p = 0.017) with IS in comparison with the corresponding controls. No significant relation was found between JHM prevalence and scoliosis angular value (p = 0.35), apical vertebra rotation (p = 0.86), the number of vertebrae within curvature (p = 0.8), the type of applied treatment (p = 0.55) and the age of subjects (p = 0.79). JHM prevalence was found to be higher in children with single curve scoliosis than in children with double curve scoliosis (p = 0.03). CONCLUSIONS: JHM occurs more frequently in children with IS than in healthy sex and age matched controls. No relation of JHM with radiological parameters, treatment type and age was found. Systematically searched in IS children, JHM should be taken into account when physiotherapy is planned. PMID- 21981905 TI - Greasing the wheels of managing overweight and obesity with omega-3 fatty acids. AB - The epidemic of overweight and obesity around the world and in the US is a major public health challenge, with 1.5 billion overweight and obese adults worldwide, and 68% of US adults and 31% of US children and adolescents overweight or obese. Obesity leads to serious health consequences, including an increased risk of type 2 diabetes mellitus and heart disease. Current preventive and medical treatments include lifestyle modification, medication, and bariatric surgery in extreme cases; however, they are either not very efficacious or are very expensive. Obesity is a complex condition involving the dysregulation of several organ systems and molecular pathways, including adipose tissue, the pancreas, the gastrointestinal tract, and the CNS. The role of the CNS in obesity is receiving more attention as obesity rates rise and treatments continue to fail. While the role of the hypothalamus in regulation of appetite and food intake has long been recognized, the roles of the CNS reward systems are beginning to be examined as the role of environmental influences on energy balance are explored. Omega-3 polyunsaturated fatty acids are essential nutrients that play a beneficial role in several disease processes due to their anti-inflammatory effects, modulation of lipids, and effects on the CNS. Omega-3 fatty acids, specifically EPA and DHA, have shown promising preliminary results in animal and human studies in the prevention and treatment of obesity. Given their effects on many of the pathways involved in obesity, and specifically in the endocannabinoid and mesocorticolimbic pathways, we hypothesize that EPA and DHA supplementation in populations can reduce the reward associated with food, thereby reduce appetite and food intake, and ultimately contribute to the prevention or reduction of obesity. If these fatty acids do harbor such potential, their supplementation in many parts of the world may hold great promise in reducing the global burden of obesity. PMID- 21981907 TI - Genomic and proteomic analyses of Mycobacterium bovis BCG Mexico 1931 reveal a diverse immunogenic repertoire against tuberculosis infection. AB - BACKGROUND: Studies of Mycobacterium bovis BCG strains used in different countries and vaccination programs show clear variations in the genomes and immune protective properties of BCG strains. The aim of this study was to characterise the genomic and immune proteomic profile of the BCG 1931 strain used in Mexico. RESULTS: BCG Mexico 1931 has a circular chromosome of 4,350,386 bp with a G+C content and numbers of genes and pseudogenes similar to those of BCG Tokyo and BCG Pasteur. BCG Mexico 1931 lacks Region of Difference 1 (RD1), RD2 and N-RD18 and one copy of IS6110, indicating that BCG Mexico 1931 belongs to DU2 group IV within the BCG vaccine genealogy. In addition, this strain contains three new RDs, which are 53 (RDMex01), 655 (RDMex02) and 2,847 bp (REDMex03) long, and 55 single-nucleotide polymorphisms representing non-synonymous mutations compared to BCG Pasteur and BCG Tokyo. In a comparative proteomic analysis, the BCG Mexico 1931, Danish, Phipps and Tokyo strains showed 812, 794, 791 and 701 protein spots, respectively. The same analysis showed that BCG Mexico 1931 shares 62% of its protein spots with the BCG Danish strain, 61% with the BCG Phipps strain and only 48% with the BCG Tokyo strain. Thirty-nine reactive spots were detected in BCG Mexico 1931 using sera from subjects with active tuberculosis infections and positive tuberculin skin tests. CONCLUSIONS: BCG Mexico 1931 has a smaller genome than the BCG Pasteur and BCG Tokyo strains. Two specific deletions in BCG Mexico 1931 are described (RDMex02 and RDMex03). The loss of RDMex02 (fadD23) is associated with enhanced macrophage binding and RDMex03 contains genes that may be involved in regulatory pathways. We also describe new antigenic proteins for the first time. PMID- 21981908 TI - New(s) to the (Z-)ring. AB - Cytokinesis in bacteria is mediated by a macromolecular machine known as the divisome, consisting of an assembly of FtsZ polymers around the cylindrical axis of the cell and the downstream regulators of division that are subsequently recruited to it. FtsZ polymerizes into filaments in a GTP-dependent manner, similarly to its eukaryotic structural homolog tubulin. The initial placement of the FtsZ polymerization site is tightly regulated by multiple mechanisms, as are the subsequent polymer reshaping and force generation that separate the two daughter cells from each other. New factors have been recently discovered that contribute to this regulation, notably affecting FtsZ polymer shaping, and modulating FtsZ polymerization in response to the metabolic or redox state of the cell. PMID- 21981909 TI - A randomized clinical trial of a peri-operative behavioral intervention to improve physical activity adherence and functional outcomes following total knee replacement. AB - BACKGROUND: Total knee replacement (TKR) is a common and effective surgical procedure to relieve advanced knee arthritis that persists despite comprehensive medical treatment. Although TKR has excellent technical outcomes, significant variation in patient-reported functional improvement post-TKR exists. Evidence suggests that consistent post-TKR exercise and physical activity is associated with functional gain, and that this relationship is influenced by emotional health. The increasing use of TKR in the aging US population makes it critical to find strategies that maximize functional outcomes. METHODS/DESIGN: This randomized clinical trial (RCT) will test the efficacy of a theory-based telephone-delivered Patient Self-Management Support intervention that seeks to enhance adherence to independent exercise and activity among post- TKR patients. The intervention consists of 12 sessions, which begin prior to surgery and continue for approximately 9 weeks post-TKR. The intervention condition will be compared to a usual care control condition using a randomized design and a probabilistic sample of men and women. Assessments are conducted at baseline, eight weeks, and six- and twelve- months. The project is being conducted at a large healthcare system in Massachusetts. The study was designed to provide greater than 80% power for detecting a difference of 4 points in physical function (SF36/Physical Component Score) between conditions (standard deviation of 10) at six months with secondary outcomes collected at one year, assuming a loss to follow up rate of no more than 15%. DISCUSSION: As TKR use expands, it is important to develop methods to identify patients at risk for sub-optimal functional outcome and to effectively intervene with the goal of optimizing functional outcomes. If shown efficacious, this peri-TKR intervention has the potential to change the paradigm for successful post-TKR care. We hypothesize that Patient Self-Management Support to enhance adherence to independent activity and exercise will enhance uniform, optimal improvement in post-TKR function and patient autonomy, the ultimate goals of TKR. PMID- 21981910 TI - Strengthening organizational performance through accreditation research-a framework for twelve interrelated studies: the ACCREDIT project study protocol. AB - BACKGROUND: Service accreditation is a structured process of recognising and promoting performance and adherence to standards. Typically, accreditation agencies either receive standards from an authorized body or develop new and upgrade existing standards through research and expert views. They then apply standards, criteria and performance indicators, testing their effects, and monitoring compliance with them. The accreditation process has been widely adopted. The international investments in accreditation are considerable. However, reliable evidence of its efficiency or effectiveness in achieving organizational improvements is sparse and the value of accreditation in cost benefit terms has yet to be demonstrated. Although some evidence suggests that accreditation promotes the improvement and standardization of care, there have been calls to strengthen its research base.In response, the ACCREDIT (Accreditation Collaborative for the Conduct of Research, Evaluation and Designated Investigations through Teamwork) project has been established to evaluate the effectiveness of Australian accreditation in achieving its goals. ACCREDIT is a partnership of key researchers, policymakers and agencies. FINDINGS: We present the framework for our studies in accreditation. Four specific aims of the ACCREDIT project, which will direct our findings, are to: (i) evaluate current accreditation processes; (ii) analyse the costs and benefits of accreditation; (iii) improve future accreditation via evidence; and (iv) develop and apply new standards of consumer involvement in accreditation. These will be addressed through 12 interrelated studies designed to examine specific issues identified as a high priority. Novel techniques, a mix of qualitative and quantitative methods, and randomized designs relevant for health-care research have been developed. These methods allow us to circumvent the fragmented and incommensurate findings that can be generated in small-scale, project-based studies. The overall approach for our research is a multi-level, multi-study design. DISCUSSION: The ACCREDIT project will examine the utility, reliability, relevance and cost effectiveness of differing forms of accreditation, focused on general practice, aged care and acute care settings in Australia. Empirically, there are potential research gains to be made by understanding accreditation and extending existing knowledge; theoretically, this design will facilitate a systems view of accreditation of benefit to the partnership, international research communities, and future accreditation designers."Accreditation of health care organisations is a multimillion dollar industry which shapes care in many countries. Recent reviews of research show little evidence that accreditation increases safety or improves quality. It's time we knew about the cost and value of accreditation and about its future direction." [Professor John Ovretveit, Karolinska Institute, Sweden, 7 October 2009]. PMID- 21981911 TI - Insulators organize chromatin: emerging rules of the game. AB - In this issue of Molecular Cell, Wood et al. (2011) provide mechanistic insight into the regulation of insulators that helps explain how they can organize chromatin in a cell type-specific fashion. PMID- 21981912 TI - Revoking the cellular license to replicate: yet another AAA assignment. AB - In this issue of Molecular Cell, Raman et al. (2011) and Franz et al. (2011) establish the AAA ATPase CDC-48/p97 as an essential regulator of eukaryotic DNA replication that coordinates the release of chromatin-bound CDT1 with its degradation by the proteasome. PMID- 21981913 TI - A double lock on sister chromatids by cohesin. AB - In this issue of Molecular Cell, Farcas et al. (2011) demonstrate that intertwining between sister chromatids at metaphase is much more significant than previously thought and, remarkably, show that it depends on cohesin. PMID- 21981914 TI - A new link in the chain from amino acids to mTORC1 activation. AB - A recent study reveals that the scaffold protein p62 plays a role in linking nutritional cues (amino acids) to the activation of mammalian target of rapamycin complex 1 (mTORC1), a protein kinase that controls cell size and proliferation. PMID- 21981916 TI - Regulation of chromatin organization and inducible gene expression by a Drosophila insulator. AB - Insulators are multiprotein-DNA complexes thought to affect gene expression by mediating inter- and intrachromosomal interactions. Drosophila insulators contain specific DNA-binding proteins plus common components, such as CP190, that facilitate these interactions. Here, we examine changes in the distribution of Drosophila insulator proteins during the heat-shock and ecdysone responses. We find that CP190 recruitment to insulator sites is the main regulatable step in controlling insulator function during heat shock. In contrast, both CP190 and DNA binding protein recruitment are regulated during the ecdysone response. CP190 is necessary to stabilize specific chromatin loops and for proper activation of transcription of genes regulated by this hormone. These findings suggest that cells may regulate recruitment of insulator proteins to DNA to activate insulator activity at specific sites and create distinct patterns of nuclear organization that are necessary to achieve proper gene expression in response to different stimuli. PMID- 21981915 TI - RIPK-dependent necrosis and its regulation by caspases: a mystery in five acts. AB - Caspase-8, FADD, and FLIP orchestrate apoptosis in response to death receptor ligation. Mysteriously however, these proteins are also required for normal embryonic development and immune cell proliferation, an observation that has led to their implication in several nonapoptotic processes. While many scenarios have been proposed, recent genetic and biochemical evidence points to unregulated signaling by the receptor-interacting protein kinases-1 (RIPK1) and RIPK3 as the lethal defect in caspase-8-, FADD-, and FLIP-deficient animals and tissues. The RIPKs are known killers, being responsible for a nonapoptotic form of cell death with features similar to necrosis. However, the mechanism by which caspase-8, FADD, and FLIP prevent runaway RIPK activation is unknown, and the signals that trigger these events during development and immune cell activation remain at large. In this review, we will lay out the evidence as it now stands, reinterpreting earlier observations in light of new clues and considering where the investigation might lead. PMID- 21981917 TI - HAT4, a Golgi apparatus-anchored B-type histone acetyltransferase, acetylates free histone H4 and facilitates chromatin assembly. AB - Histone acetyltransferases (HATs) are an essential regulatory component in chromatin biology. Unlike A-type HATs, which are found in the nucleus and utilize nucleosomal histones as substrates and thus primarily function in transcriptional regulation, B-type HATs have been characterized as cytoplasmic enzymes that catalyze the acetylation of free histones. Here, we report on a member of the GCN5-related N-acetyltransferase superfamily and another B-type HAT, HAT4. Interestingly, HAT4 is localized in the Golgi apparatus and displays a substrate preference for lysine residues of free histone H4, including H4K79 and H4K91, that reside in the globular domain of H4. Significantly, HAT4 depletion impaired nucleosome assembly, inhibited cell proliferation, sensitized cells to DNA damage, and induced cell apoptosis. Our data indicate that HAT4 is an important player in the organization and function of the genome and may contribute to the diversity and complexity of higher eukaryotic organisms. PMID- 21981918 TI - Ecdysone- and NO-mediated gene regulation by competing EcR/Usp and E75A nuclear receptors during Drosophila development. AB - The Drosophila ecdysone receptor (EcR/Usp) is thought to activate or repress gene transcription depending on the presence or absence, respectively, of the hormone ecdysone. Unexpectedly, we found an alternative mechanism at work in salivary glands during the ecdysone-dependent transition from larvae to pupae. In the absense of ecdysone, both ecdysone receptor subunits localize to the cytoplasm, and the heme-binding nuclear receptor E75A replaces EcR/Usp at common target sequences in several genes. During the larval-pupal transition, a switch from gene activation by EcR/Usp to gene repression by E75A is triggered by a decrease in ecdysone concentration and by direct repression of the EcR gene by E75A. Additional control is provided by developmentally timed modulation of E75A activity by NO, which inhibits recruitment of the corepressor SMRTER. These results suggest a mechanism for sequential modulation of gene expression during development by competing nuclear receptors and their effector molecules, ecdysone and NO. PMID- 21981919 TI - A genome-wide screen identifies p97 as an essential regulator of DNA damage dependent CDT1 destruction. AB - Several proteins, including the replication licensing factor CDT1 and the histone methyltransferase SET8, are targeted for proteolysis during DNA replication and repair by the E3 ubiquitin ligase CRL4(CDT2). CRL4(CDT2) function is coupled to replication and repair because it only ubiquitinates substrates that associate with chromatin-bound PCNA. Here, we report a genome-wide siRNA screen that identifies multiple factors necessary for CDT1 destruction after UV irradiation. Among these, nucleotide excision repair factors promote CDT1 destruction due to a role in recruiting PCNA to damaged DNA. The COP9/Signalosome regulates CDT2 stability through CUL4 deneddylation. Finally, the p97 AAA(+)-ATPase and its cofactor UFD1 are required for proteasome-dependent removal of ubiquitinated CDT1 and SET8 from chromatin and their subsequent degradation both in vivo and in a Xenopus egg extract system in vitro. This study provides insight into and a resource for the further exploration of pathways that promote timely degradation of chromatin-associated CRL4(CDT2) substrates. PMID- 21981920 TI - CDC-48/p97 coordinates CDT-1 degradation with GINS chromatin dissociation to ensure faithful DNA replication. AB - Faithful transmission of genomic information requires tight spatiotemporal regulation of DNA replication factors. In the licensing step of DNA replication, CDT-1 is loaded onto chromatin to subsequently promote the recruitment of additional replication factors, including CDC-45 and GINS. During the elongation step, the CDC-45/GINS complex moves with the replication fork; however, it is largely unknown how its chromatin association is regulated. Here, we show that the chaperone-like ATPase CDC-48/p97 coordinates degradation of CDT-1 with release of the CDC-45/GINS complex. C. elegans embryos lacking CDC-48 or its cofactors UFD-1/NPL-4 accumulate CDT-1 on mitotic chromatin, indicating a critical role of CDC-48 in CDT-1 turnover. Strikingly, CDC-48(UFD-1/NPL-4) deficient embryos show persistent chromatin association of CDC-45/GINS, which is a consequence of CDT-1 stabilization. Moreover, our data confirmed a similar regulation in Xenopus egg extracts, emphasizing a conserved coordination of licensing and elongation events during eukaryotic DNA replication by CDC-48/p97. PMID- 21981921 TI - Cohesin's concatenation of sister DNAs maintains their intertwining. AB - The contribution of DNA catenation to sister chromatid cohesion is unclear partly because it has never been observed directly within mitotic chromosomes. Differential sedimentation-velocity and gel electrophoresis reveal that sisters of 26 kb circular minichromosomes are held together by catenation as well as by cohesin. The finding that chemical crosslinking of cohesin's three subunit interfaces entraps sister DNAs of circular but not linear minichromosomes implies that cohesin functions using a topological principle. Importantly, cohesin holds both catenated and uncatenated DNAs together in this manner. In the vicinity of centromeres, catenanes are resolved by spindle forces, but linkages mediated directly by cohesin resist these forces even after complete decatenation. Crucially, persistence of catenation after S phase depends on cohesin. We conclude that by retarding Topo II-driven decatenation, cohesin mediates sister chromatid cohesion by an indirect mechanism as well as one involving entrapment of sister DNAs inside its tripartite ring. PMID- 21981922 TI - A Pre-mRNA degradation pathway that selectively targets intron-containing genes requires the nuclear poly(A)-binding protein. AB - General discard pathways eliminate unprocessed and irregular pre-mRNAs to control the quality of gene expression. In contrast to such general pre-mRNA decay, we describe here a nuclear pre-mRNA degradation pathway that controls the expression of select intron-containing genes. We show that the fission yeast nuclear poly(A) binding protein, Pab2, and the nuclear exosome subunit, Rrp6, are the main factors involved in this polyadenylation-dependent pre-mRNA degradation pathway. Transcriptome analysis and intron swapping experiments revealed that inefficient splicing is important to dictate susceptibility to Pab2-dependent pre-mRNA decay. We also show that negative splicing regulation can promote the poor splicing efficiency required for this pre-mRNA decay pathway, and in doing so, we identified a mechanism of cross-regulation between paralogous ribosomal proteins through nuclear pre-mRNA decay. Our findings unveil a layer of regulation in the nucleus in which the turnover of specific pre-mRNAs, besides the turnover of mature mRNAs, is used to control gene expression. PMID- 21981923 TI - GW182 proteins directly recruit cytoplasmic deadenylase complexes to miRNA targets. AB - miRNAs are posttranscriptional regulators of gene expression that associate with Argonaute and GW182 proteins to repress translation and/or promote mRNA degradation. miRNA-mediated mRNA degradation is initiated by deadenylation, although it is not known whether deadenylases are recruited to the mRNA target directly or by default, as a consequence of a translational block. To answer this question, we performed a screen for potential interactions between the Argonaute and GW182 proteins and subunits of the two cytoplasmic deadenylase complexes. We found that human GW182 proteins recruit the PAN2-PAN3 and CCR4-CAF1-NOT deadenylase complexes through direct interactions with PAN3 and NOT1, respectively. These interactions are critical for silencing and are conserved in D. melanogaster. Our findings reveal that GW182 proteins provide a docking platform through which deadenylase complexes gain access to the poly(A) tail of miRNA targets to promote their deadenylation, and they further indicate that deadenylation is a direct effect of miRNA regulation. PMID- 21981924 TI - p62 is a key regulator of nutrient sensing in the mTORC1 pathway. AB - The signaling adaptor p62 is a critical mediator of important cellular functions, owing to its ability to establish interactions with various signaling intermediaries. Here, we identify raptor as an interacting partner of p62. Thus, p62 is an integral part of the mTORC1 complex and is necessary to mediate amino acid signaling for the activation of S6K1 and 4EBP1. p62 interacts in an amino acid-dependent manner with mTOR and raptor. In addition, p62 binds the Rags proteins and favors formation of the active Rag heterodimer that is further stabilized by raptor. Interestingly, p62 colocalizes with Rags at the lysosomal compartment and is required for the interaction of mTOR with Rag GTPases in vivo and for translocation of the mTORC1 complex to the lysosome, a crucial step for mTOR activation. PMID- 21981925 TI - Mechanism of USP7/HAUSP activation by its C-terminal ubiquitin-like domain and allosteric regulation by GMP-synthetase. AB - The ubiquitin-specific protease USP7/HAUSP regulates p53 and MDM2 levels, and cellular localization of FOXO4 and PTEN, and hence is critically important for their role in cellular processes. Here we show how the 64 kDa C-terminal region of USP7 can positively regulate deubiquitinating activity. We present the crystal structure of this USP7/HAUSP ubiquitin-like domain (HUBL) comprised of five ubiquitin-like (Ubl) domains organized in 2-1-2 Ubl units. The last di-Ubl unit, HUBL-45, is sufficient to activate USP7, through binding to a "switching" loop in the catalytic domain, which promotes ubiquitin binding and increases activity 100 fold. This activation can be enhanced allosterically by the metabolic enzyme GMPS. It binds to the first three Ubl domains (HUBL-123) and hyperactivates USP7 by stabilization of the HUBL-45-dependent active state. PMID- 21981926 TI - Acetylation regulates the stability of a bacterial protein: growth stage dependent modification of RNase R. AB - RNase R, an Escherichia coli exoribonuclease important for degradation of structured RNAs, increases 3- to 10-fold under certain stress conditions, due to an increased half-life for this usually unstable protein. Components of the trans translation machinery, tmRNA, and its associated protein, SmpB, are essential for RNase R instability. However, it is not understood why exponential phase RNase R is unstable or how it becomes stabilized in stationary phase. Here, we show that these phenomena are regulated by acetylation catalyzed by YfiQ protein. One residue, Lys544, is acetylated in exponential phase RNase R, but not in the stationary phase protein, resulting in tighter binding of tmRNA-SmpB to the C terminal region of exponential phase RNase R and subsequent proteolytic degradation. Removal of the positive charge at Lys544 or a negative charge in the C-terminal region likely disrupts their interaction, facilitating tmRNA-SmpB binding. These findings indicate that acetylation can regulate the stability of a bacterial protein. PMID- 21981928 TI - [Reversing ICU-acquired immunosuppression: an innovative biomarker-guided therapeutic strategy for decreasing sepsis mortality and nosocomial infection rate]. AB - Septic syndromes (systemic inflammatory response associated with infection) remain a major although largely under-recognized health care problem and represent the first cause of mortality in intensive care units. Regarding immune response, it is now agreed that sepsis induces an anti-inflammatory process, acting as a negative feedback. This inhibitory mechanism becomes deleterious as nearly all immune functions are rapidly compromised. The magnitude and persistence over time of this immunosuppression is correlated with nosocomial infections and mortality. Decreased HLA-DR expression on monocytes/increased percentage of regulatory T cells are biomarkers identifying patients at risk who could benefit from immunotherapy. This review attempts to integrate these new facts into an up-to-date account of sepsis pathophysiology. PMID- 21981927 TI - Use of mefloquine in children - a review of dosage, pharmacokinetics and tolerability data. AB - BACKGROUND: Use of anti-malarial medication in children is hampered by a paucity of dosage, pharmacokinetic and tolerability data. METHODS: Data on the use of mefloquine in children, particularly in young children weighing less than 20 kg, were reviewed using PubMed literature and reports on file. RESULTS: Chemoprophylaxis data: Two studies with a total of 170 children were found. A simulated mefloquine plasma profile showed that doses to achieve protective chemoprophylaxis blood concentration of mefloquine of approximately 620 ng/mL (or 1.67 MUmol/L) in children should be at least 5 mg/kg. This simulated plasma profile in children corresponds to that seen in adult travellers using a weekly prophylaxis dose of 250 mg. This reinforces current practice of using weight based dosage for children. Clearance per body weight is higher in older children. For children who travel to malaria risk areas tablets can be broken and crushed as required. It is necessary to disguise the bitter taste of the drug. Treatment data: Mefloquine treatment (alone or in combination) data are available for more than 6000 children of all age and weight categories. The stereoselectivity and pharmacokinetic profile of mefloquine in children is similar to that observed in adults. There is higher clearance in older children (aged 5-12 years) compared to younger children (aged 6-24 months). Mefloquine treatment is well tolerated in infants (5-12 kg) but vomiting is a problem at high doses. This led to the use of a "split dose" regimen with 15 mg/kg initially, followed 12 hours later by 10 mg/kg. Mefloquine 125 mg has been used as intermittent preventive treatment (IPT) and was found to be efficacious in reducing episodes of malaria in a moderate transmission setting but vomiting was a problem in 8% of children aged 2-11 months. Mefloquine is also used as a component of artemisinin combination therapy (ACT) in small children. The combination artesunate plus mefloquine is a WHO approved first-line treatment for uncomplicated malaria in Africa. CONCLUSION: Currently available data provide a scientific basis for the use of mefloquine in small children in the chemoprophylaxis setting and as a part of treatment regimens for children living in endemic areas. PMID- 21981929 TI - Green synthesis of biogenic metal nanoparticles by terrestrial and aquatic phototrophic and heterotrophic eukaryotes and biocompatible agents. AB - The size, shape and controlled dispersity of nanoparticles play a vital role in determining the physical, chemical, optical and electronic properties attributing its applications in environmental, biotechnological and biomedical fields. Various physical and chemical processes have been exploited in the synthesis of several inorganic metal nanoparticles by wet and dry approaches viz., ultraviolet irradiation, aerosol technologies, lithography, laser ablation, ultrasonic fields, and photochemical reduction techniques. However, these methodologies remain expensive and involve the use of hazardous chemicals. Therefore, there is a growing concern for the development of alternative environment friendly and sustainable methods. Increasing awareness towards green chemistry and biological processes has led to a necessity to develop simple, cost-effective and eco friendly procedures. Phototrophic eukaryotes such as plants, algae, and diatoms and heterotrophic human cell lines and some biocompatible agents have been reported to synthesize greener nanoparticles like cobalt, copper, silver, gold, bimetallic alloys, silica, palladium, platinum, iridium, magnetite and quantum dots. Owing to the diversity and sustainability, the use of phototrophic and heterotrophic eukaryotes and biocompatible agents for the synthesis of nanomaterials is yet to be fully explored. This review describes the recent advancements in the green synthesis and applications of metal nanoparticles by plants, aquatic autotrophs, human cell lines, biocompatible agents and biomolecules. PMID- 21981930 TI - The rush to publish. PMID- 21981933 TI - Cortical thickness in neuropsychologically near-normal schizophrenia. AB - Schizophrenia is a severe psychiatric illness with widespread impairments of cognitive functioning; however, a certain percentage of subjects are known to perform in the normal range on neuropsychological measures. While the cognitive profiles of these individuals have been examined, there has been relatively little attention to the neuroanatomical characteristics of this important subgroup. The aims of this study were to statistically identify schizophrenia subjects with relatively normal cognition, examine their neuroanatomical characteristics relative to their more impaired counterparts using cortical thickness mapping, and to investigate relationships between these characteristics and demographic variables to better understand the nature of cognitive heterogeneity in schizophrenia. Clinical, neuropsychological, and MRI data were collected from schizophrenia (n = 79) and healthy subjects (n = 65). A series of clustering algorithms on neuropsychological scores was examined, and a 2-cluster solution that separated subjects into neuropsychologically near-normal (NPNN) and neuropsychologically impaired (NPI) groups was determined most appropriate. Surface-based cortical thickness mapping was utilized to examine differences in thinning among schizophrenia subtypes compared with the healthy participants. A widespread cortical thinning pattern characteristic of schizophrenia emerged in the NPI group, while NPNN subjects demonstrated very limited thinning relative to healthy comparison subjects. Analysis of illness duration indicated minimal effects on subtype classification and cortical thickness results. Findings suggest a strong link between cognitive impairment and cortical thinning in schizophrenia, where subjects with near-normal cognitive abilities also demonstrate near-normal cortical thickness patterns. While generally supportive of distinct etiological processes for cognitive subtypes, results provide direction for further examination of additional neuroanatomical differences. PMID- 21981934 TI - The effect of technology information on consumer expectations and liking of beef. AB - European consumers increasingly attach value to process characteristics of food. Although beef technologies are hardly communicated to consumers, providing consumer-oriented information about technology application might increase perceived transparency and consumer acceptance. This study investigates how information about beef technologies influences consumer expectations and liking of beef. Beef consumers in Belgium (n = 108) and Norway (n = 110) participated in an information experiment combined with sensory testing in which each consumer tasted three beef muscles treated with different technologies: unprocessed tenderloin M. Psoas major, muscle profiled M. Infraspinatus, and marinated (by injection) M. Semitendinosus. The findings indicate that detailed information about beef technologies can enhance consumers' expectations and liking of beef. However, this effect differs between countries and beef technologies. Information becomes either less relevant when the product is actually tasted, as indicated by the findings in Norway, or more relevant when information is confirmed by own experience during tasting, as indicated by the findings in Belgium. PMID- 21981935 TI - The role of the acquisition methods in the analysis of natural and synthetic steroids and cholic acids by gas chromatography-mass spectrometry. AB - An exhaustive GC-MS acquisition study was performed, for the simultaneous analysis of natural and synthetic steroids and cholic acids (in order to insert them into the last tierce of our multiresidue analysis system), such as androsterone, beta-estradiol, transdehydroandro-sterone, transdehyroandrosterone, mestranol, dihydrotestosterone, ethinylestradiol, testosterone, norethisterone, estriol, 4-androstene-3,17-dione, gestodene, levonorgestrel, etonogestrel, coprostanol, progesterone, cholesterol, medroxyprogesterone-acetate, lithocholic acid, stigmasterol, cholic acid, chenodeoxycholic acid, beta-sitosterol, ursodeoxycholic acid, 3-hydroxy-7-ketocholic acid and dehydrocholic acid, in total 26 compounds. As novelties to the field, for the trimethylsilyl (TMS) oxime ether/ester derivatives of steroids and cholic acids, at first, a tandem mass spectrometric (MS/MS), multiple reaction monitoring (MRM) type acquisition method has been developed in a single run; also for the first time, the three acquisition techniques, the full scan (FS), the selective ion monitoring (SIM), in our case the multiple ion monitoring (MIM) and the currently optimized MRM methods, have been compared; all three, in parallel, under strictly the same derivatization/instrumental conditions, both in matrix free solutions and municipal wastewater from two Hungarian wastewater treatment plants (WWTPs). Critical evaluation of the three acquisition protocols was collated on their analytical performances and validated under the same conditions. The data of six point calibration curves for FS, MIM and MRM methods, showed that both R2 (0.9995, 0.9858, 0.9975) and RSD (5.3, 5.8, 5.0), for two parallel derivatizations, each injected three times, proved to be independent of the acquisition processes. Whereas, for the method limit of quantification (LOQ) and the instrument limit of quantification (ILQ) values showed considerable differences. LOQ data, were decreasing in the FS, MIM, MRM line (expressed in ng/L), for all steroids and cholic acids. The same trend was determined in terms of the ILQ values. The practical utility of the optimized acquisition techniques was confirmed by the quantitation of the steroids and cholic acids contents of wastewater samples. Results confirmed the importance of the MRM acquisition method, even in comparison to the MIM one: with particular interest in selected cases: avoiding the extreme overestimation of the beta-estradiol (156-1325%) and that of the ethinylestradiol (582-831%) concentrations in the wastewater samples. PMID- 21981936 TI - Drug eruption caused by sitagliptin, a dipeptidyl peptidase-IV inhibitor. PMID- 21981937 TI - [Continuous renal replacement therapies and antifungal drugs: an essential review]. PMID- 21981938 TI - [Disseminated infection due to mycobacterium abscessus in an HIV-infected patient]. PMID- 21981939 TI - [Eosinophilia and a subcutaneous nodule in patient from Equatorial Guinea]. PMID- 21981940 TI - Pneumonia without the need for admission, the experience in an emergency department. PMID- 21981941 TI - Molecular structure, vibrational spectroscopic, first-order hyperpolarizability and HOMO, LUMO studies of 2-aminobenzimidazole. AB - In the present work, we reported a combined experimental and theoretical study on molecular structure, vibrational spectra and HOMO-LUMO analysis of 2 aminobenzimidazole (2-ABD). The FTIR (400-4000 cm(-1)) and FT-Raman spectra (50 3500 cm(-1)) of 2-ABD were recorded. The molecular geometry, harmonic vibrational wavenumbers and bonding features of 2-ABD in the ground-state have been calculated by using the density functional B3LYP method with 6-311++G(d,p) and 6 31G(d) as basis sets. The energy and oscillator strength were calculated by time dependent density functional theory (TD-DFT) result complements with the experimental findings. The calculated HOMO and LUMO energies showed that charge transfer occurs within the molecule. Finally, the calculation results were applied to simulate infrared and Raman spectra of the title compound which showed good agreement with the observed spectra. PMID- 21981942 TI - Spectroscopic studies of dactinomycin and vinorelbine binding to deoxyribonucleic acid and chromatin. AB - Dactinomycin and vinorelbine are anticancer drugs, widely used as chemotherapeutic agents for the treatment of various cancers. This study represents an attempt to compare the effect of these drugs on DNA and soluble chromatin employing UV/vis, fluorescence and circular dichroism spectroscopy techniques. The results demonstrated that the absorbance at 260 and 210 nm was decreased and quenching of drugs with DNA and chromatin chromospheres induced reduction of fluorescence emission intensity. Circular dichroism profiles showed that the binding of drugs induced structural changes in both positive and negative extremes of DNA and chromatin revealing release or displacement of histone proteins from chromatin upon dactinomycin binding whereas vinorelbine preceded the chromatin into compaction. The results suggest that dactinomycin shows higher affinity to DNA compared to chromatin, whereas, vinorelbine recognizes the chromatin structure with higher affinity than free DNA. Also chromatin proteins play a fundamental role in drug-chromatin complex process. PMID- 21981943 TI - Determination of oil wells productivity using multivariate FTIR data. AB - Traditional methods for productivity surveillance of oil wells mainly are consisted of using test-separator units with expensive devices, protections, inspections, operations, facilities, infrastructures and repairing services. The objective of this work is to utilize a novel approach to predict the accurate productivity of oil wells using a single sample point at the line of blend oil. The present method is based upon performing multivariate regression of infrared spectra, which taken from the real samples of Iranian offshore oil wells. The experimental results revealed that the present approach is appropriate for precocious, quick and reliable surveillance of individual oil wells located in an oil field. The model has predicted the accurate productivity of real oil wells with respect to the current expensive techniques since 2010. PMID- 21981944 TI - Experimental IR and Raman spectra and quantum chemical studies of molecular structures, conformers and vibrational characteristics of L-ascorbic acid and its anion and cation. AB - IR and spectra of the L-ascorbic acid (L-AA) also known as vitamin C have been recorded in the region 4000-50 cm(-1). In order to make vibrational assignments of the observed IR and Raman bands computations were carried out by employing the RHF and DFT methods to calculate the molecular geometries and harmonic vibrational frequencies along with other related parameters for the neutral L-AA and its singly charged anionic (L-AA(-)) and cationic (L-AA(+)) species. Significant changes have been found for different characteristics of a number of vibrational modes. The four nu(O-H) modes of the L-AA molecule are found in the order nu(O(9)-H(10))>nu(O(19)-H(20))>nu(O(7)-H(8))>nu(O(14)-H(15)) which could be due to complexity of hydrogen bonding in the lactone ring and the side chain. The CO stretching wavenumber (nu(46)) decreases by 151 cm(-1) in going from the neutral to the anionic species whereas it increases by 151 cm(-1) in going from the anionic to the cationic species. The anionic radicals have less kinetic stabilities and high chemical reactivity as compared to the neutral molecule. It is found that the cationic radical of L-AA is kinetically least stable and chemically most reactive as compared to its neutral and anionic species. PMID- 21981945 TI - Liposomal doxorubicin improves radiotherapy response in hypoxic prostate cancer xenografts. AB - BACKGROUND: Tumor vasculature frequently fails to supply sufficient levels of oxygen to tumor tissue resulting in radioresistant hypoxic tumors. To improve therapeutic outcome radiotherapy (RT) may be combined with cytotoxic agents. METHODS: In this study we have investigated the combination of RT with the cytotoxic agent doxorubicin (DXR) encapsulated in pegylated liposomes (PL-DXR). The PL-DXR formulation Caelyx was administered to male mice bearing human, androgen-sensitive CWR22 prostate carcinoma xenografts in a dose of 3.5 mg DXR/kg, in combination with RT (2 Gy/day * 5 days) performed under normoxic and hypoxic conditions. Hypoxic RT was achieved by experimentally inducing tumor hypoxia by clamping the tumor-bearing leg five minutes prior to and during RT. Treatment response evaluation consisted of tumor volume measurements and dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) with subsequent pharmacokinetic analysis using the Brix model. Imaging was performed pre treatment (baseline) and 8 days later. Further, hypoxic fractions were determined by pimonidazole immunohistochemistry of excised tumor tissue. RESULTS: As expected, the therapeutic effect of RT was significantly less effective under hypoxic than normoxic conditions. However, concomitant administration of PL-DXR significantly improved the therapeutic outcome following RT in hypoxic tumors. Further, the pharmacokinetic DCE MRI parameters and hypoxic fractions suggest PL DXR to induce growth-inhibitory effects without interfering with tumor vascular functions. CONCLUSIONS: We found that DXR encapsulated in liposomes improved the therapeutic effect of RT under hypoxic conditions without affecting vascular functions. Thus, we propose that for cytotoxic agents affecting tumor vascular functions liposomes may be a promising drug delivery technology for use in chemoradiotherapy. PMID- 21981946 TI - The rgg0182 gene encodes a transcriptional regulator required for the full Streptococcus thermophilus LMG18311 thermal adaptation. AB - BACKGROUND: Streptococcus thermophilus is an important starter strain for the production of yogurt and cheeses. The analysis of sequenced genomes of four strains of S. thermophilus indicates that they contain several genes of the rgg familly potentially encoding transcriptional regulators. Some of the Rgg proteins are known to be involved in bacterial stress adaptation. RESULTS: In this study, we demonstrated that Streptococcus thermophilus thermal stress adaptation required the rgg0182 gene which transcription depends on the culture medium and the growth temperature. This gene encoded a protein showing similarity with members of the Rgg family transcriptional regulator. Our data confirmed that Rgg0182 is a transcriptional regulator controlling the expression of its neighboring genes as well as chaperones and proteases encoding genes. Therefore, analysis of a Deltargg0182 mutant revealed that this protein played a role in the heat shock adaptation of Streptococcus thermophilus LMG18311. CONCLUSIONS: These data showed the importance of the Rgg0182 transcriptional regulator on the survival of S. thermophilus during dairy processes and more specifically during changes in temperature. PMID- 21981947 TI - On becoming a T cell, a convergence of factors kick it up a Notch along the way. AB - The thymus is seeded by bone marrow-derived progenitors, which undergo a series of differentiation and proliferation events in order to generate functional T lymphocytes. The Notch signaling pathway, together with multiple transcription factors, act in concert to commit progenitors to a T-lineage fate, extinguishing non-T cell potential, inducing thymocyte differentiation and supporting proliferation and survival along the way to becoming a mature T cell. This review focuses on recent evidence regarding the complex interplay between the Notch pathway and other key transcription factors at specific lineage-decision points during the program of T cell development. PMID- 21981948 TI - A diagnostic challenge for Schistosomiasis japonica in China: consequences on praziquantel-based morbidity control. AB - Worldwide schistosomiasis continues to be a serious public health problem. Over the past five decades, China has made remarkable progress in reducing Schistosoma japonicum infections in humans to a relatively low level. Endemic regions are currently circumscribed in certain core areas where re-infection and repeated chemotherapy are frequent. At present, selective chemotherapy with praziquantel is one of the main strategies in China's National Schistosomiasis Control Program, and thus diagnosis of infected individuals is a key step for such control. In this paper we review the current status of our knowledge about diagnostic tools for schistosomiasis japonica. A simple, affordable, sensitive, and specific assay for field diagnosis of schistosomiasis japonica is not yet available, and this poses great barriers towards full control of schistosomiasis. Hence, a search for a diagnostic approach, which delivers these characteristics, is essential and should be given high priority. PMID- 21981949 TI - Genomics in pediatric endocrinology-genetic disorders and new techniques. AB - In the last few years, there have been remarkable advances in the development of new and more sophisticated genetic techniques. These have allowed a better understanding of the molecular mechanisms of genetically determined pediatric endocrine disorders and are paving the way for a radical change in diagnosis and treatment. This article introduces some of these concepts and some of the genetic techniques being used. PMID- 21981950 TI - Perinatal endocrinology: common endocrine disorders in the sick and premature newborn. AB - Endocrine disorders are common in infants in the neonatal ICU. They often are associated with prematurity, low birth weight or very low birth weight, and small size for gestational age. They also frequently occur in infants who are critically ill or stressed. This article describes the most common conditions and current knowledge regarding management. PMID- 21981951 TI - Congenital disorders of the thyroid: hypo/hyper. AB - This article summarizes the ontogenesis and genetics of the thyroid with regards to its possible congenital dysfunction and briefly refers to the roles of the mother-placenta-fetal unit, iodine effect, and organic and functional changes of the negative feedback mechanism, as well as maturity and illness, in some forms of congenital hypo- and hyperthyroidism. This article also describes the published literature and the authors' data on the clinical aspects of congenital hypothyroidism, on the alternating hypo- and hyperthyroidism in the neonatal period, and on neonatal hyperthyroidism. PMID- 21981952 TI - Nutrition and bone growth in pediatrics. AB - Children's growth is a hallmark of their normal development and the association between nutrition and linear growth in children is well accepted. Growth requires an adequate supply of many different nutritional factors, some form the "building materials," whereas others play regulatory roles. In this article we describe the growth of the growth plate and discuss the role of nutritional affected hormones on this process. In addition we describe the effect of local regulators and nutritional factors on the growth process and suggest the involvement of new regulatory factors in the translation of nutrition to growth. PMID- 21981953 TI - Growth hormone: the expansion of available products and indications. AB - Growth hormone is a widely used hormone. This article describes its historical use, current indications and studies for possible future uses. PMID- 21981954 TI - Strategies for maximizing growth in puberty in children with short stature. AB - The approach to the child with growth retardation who is in puberty remains an important clinical challenge. The use of high-dose growth hormone (GH), suppression of puberty with GnRH analogs in combination with GH, and the use of selective inhibitors of the aromatase enzyme with aromatase inhibitors (also in combination with GH) are all therapeutic choices that have been studied. Aromatase blockade effectively blocks estrogen production in males with a reciprocal increase in testosterone, and a new generation of aromatase inhibitors, including anastrozole, letrozole and exemestane, is under investigation in adolescent subjects with severe growth retardation. This class of drugs, if judiciously used for a window of time, offers promise as an adjunct treatment of growth delay in pubertal patients with GH deficiency, idiopathic short stature, testotoxicosis, and other disorders of growth. These evolving uses of aromatase inhibitors, however, represent off-label use of the product, and definitive data on their efficacy are not available for each of the conditions mentioned. Safety issues regarding bone health also require further study. PMID- 21981956 TI - Optimizing potential for fertility: fertility considerations for the pediatrician. AB - Whether for the prepubertal or pubertal child, the goal of fertility preservation is to obtain cells or tissues to be used to produce future children. For the prepubertal child, preservation efforts involve germ cells, earlier forms of sperm, and immature follicles, rather than mature spermatozoa or follicles. Options for prepubertal children include for boys freezing testicular tissue and extracting testicular sperm or for girls obtaining ovarian cortical or follicular tissue for storage. These procedures involve extraction and storage of immature gametes for subsequent in vitro maturation, although attempts for sperm currently involve only animal studies. For adolescent subjects who have sufficient gonadal development and reserve, sperm, oocytes, and ovarian cortex can be retrieved as among adults. PMID- 21981955 TI - Etiology and treatment of hypogonadism in adolescents. AB - Adequate functioning at all levels of the hypothalamic-pituitary-gonadal axis is necessary for normal gonadal development and subsequent sex steroid production. Deficiencies at any level of the axis can lead to a hypogonadal state. The causes of hypogonadism are heterogeneous and may involve any level of the reproductive system. This review discusses various causes of hypogonadism, describes the evaluation of hypogonadal states, and outlines treatment options for the induction of puberty in affected adolescents. Whereas some conditions are clearly delineated, the exact etiology and underlying pathogenesis of many disorders is unknown. PMID- 21981958 TI - Metabolic syndrome in pediatrics: old concepts revised, new concepts discussed. AB - The worldwide epidemic of childhood obesity in the last decades is responsible for the occurrence in pediatrics of disorders once mainly found in adults, such as the metabolic syndrome. A key factor in the pathogenesis of metabolic syndrome is insulin resistance, a phenomenon occurring mainly in obese subjects with a general resistance to the insulin effect only on carbohydrates metabolism. Given that the metabolic syndrome is driven by obesity, the prevalence of the latter will strongly influence the prevalence of metabolic syndrome. This article addresses the causes of metabolic syndrome and the relevance of obesity in the pediatric population. PMID- 21981957 TI - Pediatric obesity: etiology and treatment. AB - This article reviews factors that contribute to excessive weight gain in children and outlines current knowledge regarding approaches for treating pediatric obesity. Most of the known genetic causes of obesity primarily increase energy intake. Genes regulating the leptin signaling pathway are particularly important for human energy homeostasis. Obesity is a chronic disorder that requires long term strategies for management. The foundation for all treatments for pediatric obesity remains restriction of energy intake with lifestyle modification. There are few long-term studies of pharmacotherapeutic interventions for pediatric obesity. Bariatric surgical approaches are the most efficacious treatment but, because of their potential risks, are reserved for those with the most significant complications of obesity. PMID- 21981959 TI - Prevention of type 1 diabetes. AB - Prevention of loss of b cells in type 1 diabetes is a major goal of current research. Knowledge of the genetic susceptibility, increasing ability to predict who may be at risk, recognition of the potential clinical impact of residual insulin secretion after diagnosis, and development of new immunomodulatory agents have supported an increasing number of clinical trials to prevent b-cell loss. Interventions can be targeted at 3 stages: before the development of autoimmunity (primary prevention), after autoimmunity is recognized (secondary prevention), or after diagnosis when significant numbers of b cells remain (tertiary prevention). Thus far, several agents show promise when given shortly after diagnosis, but no interventions before diagnosis have shown benefit. Knowledge in this area has grown quickly in recent years and will continue to grow rapidly with several international collaborative efforts underway. PMID- 21981960 TI - Pediatric disorders of water balance. AB - Fluid homeostasis requires adequate water intake, regulated by an intact thirst mechanism and appropriate free water excretion by the kidneys, mediated by appropriate secretion of arginine vasopressin (AVP, also known as antidiuretic hormone). AVP exerts its antidiuretic action by binding to the X chromosome encoded V2 vasopressin receptor (V2R), a G protein coupled receptor on the basolateral membrane of renal collecting duct epithelial cells. After V2R activation, increased intracellular cyclic adenosine monophosphate mediates shuttling of the water channel aquaporin 2 to the apical membrane of collecting duct cells, resulting in increased water permeability and antidiuresis. Clinical disorders of water balance are common, and abnormalities in many steps involving AVP secretion and responsiveness have been described. This article focuses on the principal disorders of water balance, diabetes insipidus, and the syndrome of inappropriate antidiuretic hormone secretion. PMID- 21981961 TI - Steroid 21 hydroxylase deficiency congenital adrenal hyperplasia. AB - Steroid 21 hydroxylase deficiency is the most common form of congenital adrenal hyperplasia (CAH). The severity of this disorder depends on the extent of impaired enzymatic activity, which is caused by various mutations of the 21 hydroxylase gene. This article reviews adrenal steroidogenesis and the pathophysiology of 21 hydroxylase deficiency. The three forms of CAH are then discussed in terms of clinical presentation, diagnosis and treatment, and genetic basis. Prenatal diagnosis and treatment are also reviewed. The goal of therapy is to correct the deficiency in cortisol secretion and suppress androgen overproduction. Glucocorticoid replacement has been the mainstay of treatment for CAH, but new treatment strategies continue to be developed and studied. PMID- 21981962 TI - Recent consensus statements in pediatric endocrinology: a selective review. AB - Clinical guidelines and consensus statements serve to summarize and organize current knowledge on diverse subjects and provide practical guidelines for proper clinical management. Recommendations should be based on research and evidence derived from appropriate sources. In 2008, more than 20 consensus statements were published in the pediatric literature alone. This article summarizes the salient points of the latest consensus statements jointly developed by multiple endocrine societies including the Lawson Wilkins Society for Pediatric Endocrinology and the European Society for Pediatric Endocrinology. As much as possible, the original intent and language of the statements was respected and paraphrased. PMID- 21981963 TI - Pediatric endocrinology. Preface. PMID- 21981964 TI - Use of iQPR-H2O for bone regeneration and its potential in the improvement of osteoporosis. AB - BACKGROUND: Current treatments for osteoporosis are associated with various side effects and do not prevent the age-related decrease in osteoblast number. The objective of this study was to evaluate the effects of iQPR-H2O on osteogenesis. METHODS: Mouse fibroblast NIH3T3 and pre-osteoblastic MC3T3-E1 cells were cultured in medium prepared with iQPR-H2O or unprocessed mineral water (control cells), and proliferation and differentiation were assessed by MTT and alkaline phosphatase assay, respectively. Mineral deposition by the cells was determined using Alizarin red S staining. A mouse model of osteoporosis, ovariectomized SAMP8 mice, was used to evaluate the effects of iQPR-H2O on osteogenesis in vivo. Mice were given either iQPR-H2O or unprocessed mineral water (control group) for four months after which bone mass density (BMD) measurements were made using a bone densitometer and hematoxylin and eosin staining of bone samples. RESULTS: NIH3T3 cells grown in medium prepared with iQPR-H2O exhibited significantly greater proliferation. NIH3T3 and MC3T3-E1 cells demonstrated a significant increase in alkaline phosphatase levels in the iQPR-H2O group. MC3T3-E1 cells showed mineralization at day 28. mRNA expression levels of both osteopontin and runt-related transcription factor 2 in MC3T3-E1 cells were higher in the iQPR-H2O group compared with the control group. After four months, significantly greater bone regeneration was evident in ovariectomized SAMP8 mice administered iQPR-H2O as compared with control group. CONCLUSIONS: iQPR-H2O may reduce the symptoms of osteoporosis by improving osteogenesis. PMID- 21981965 TI - [Online training tools in radiology]. AB - The online resources offered on the Internet have become complements or even alternatives to traditional resources for acquiring new knowledge. Among other advantages, online training tools are accessible 24 hours a day from anywhere provided there is an internet connection. Furthermore, there is no limit to the number of simultaneous users of these resources, and users can communicate easily with the authors of the content regardless of where they are located. This article reviews the educational resources that are available on the Internet that can be useful for training in radiology. We consider that creating and promoting this type of tool should form part of the strategic plans of professional associations of radiologists. PMID- 21981966 TI - [Percutaneous laser disc decompression for lumbar discogenic radicular pain]. AB - PURPOSE: The aim of our study was to directly evaluate the effectiveness of percutaneous laser disc decompression (PLDD) for treatment of lumbar discogenic radicular pain. MATERIALS AND METHODS: From June 2006 through July 2009, 205 patients with contained disc herniation demonstrated on computed tomography (CT) or magnetic resonance, concordance between the radicular pain and the nerve root compressed by the herniated disc, neurological findings referring to a single nerve root and no improvement after conservative therapy for a minimum of six weeks were enrolled. All patients were treated with PLDD under CT guidance and local anaesthesia. Follow-up was scheduled at 1, 2 days, 3, 6 months. Subsequent follow-ups at 12, 24 and 36 months were carried out through visits or by telephone. Clinical outcome was quantified using the MacNab criteria. RESULTS: The age of patients ranged from 27 to 78 years (mean 58+/-11 years). The levels of involvement were 18 cases at L3-L4, 123 cases at L4-L5 and 64 cases at L5-S1. Using the MacNab criteria, the results were as follows: 67% (n=137) showed a good outcome and 9% (n=18) a fair outcome. There were no serious complications in our series. CONCLUSION: PLDD is effective treatment for lumbar discogenic radicular pain, associated with only minimal discomfort to the patient. This minimally invasive technique is a valid alternative for those patients not responding to conservative medical treatment, allowing in many cases to obviate the need of spine surgery. PMID- 21981967 TI - [Summary of the information sheet for users: breastfeeding]. PMID- 21981969 TI - Bright luminescent, colloidal stable silica coated CdSe/ZnS nanocomposite by an in situ, one-pot surface functionalization. AB - In this article, a systematic study of the design and development of surface modification schemes for silica coated nanocomposite via an in situ, one-pot way is presented. Silica coated CdSe/ZnS nanoparticles were prepared in a water-in oil microemulsion and subsequently surface modified via addition of various organosilane reagents to the microemulsion system. The resulting functionalized composite nanoparticles were characterized by different techniques like Transmission Electron Microscopy (TEM), photoluminescence spectroscopy and zeta potential measurements. The results demonstrate that depending on the sequence of addition of silica precursors and organosilanes the product can show bright luminescence or considerable colloidal stability. The organosilanes molecules which are used here, act both as a stabilizer of the microemulsion system (regarding the charge compensation) and as a functional group the final product on top of silica shell. Using these surface-modification process, silica coated nanoparticles can be more readily conjugated with biomolecules and used as highly luminescent, sensitive, and reproducible labels in bioanalytical applications. Most importantly such surface functionalization could pave the way for controlled multi-mixed nanoparticles encapsulation (for example magnetic and QD nanoparticles). PMID- 21981970 TI - Interfacial tension of evaporating emulsion droplets containing amphiphilic block copolymers: effects of solvent and polymer composition. AB - Evaporating droplets of volatile organic solvent containing amphiphilic block copolymers may undergo hydrodynamic instabilities that lead to dispersal of copolymer micelles into the surrounding aqueous phase. As for related phenomena in reactive polymer blends and oil/water/surfactant systems, this process has been ascribed to a nearly vanishing or transiently negative interfacial tension between the water and solvent phases induced by adsorption of copolymer to the interface. In this report, we investigate the influence of the choice of organic solvent and polymer composition for a series of polystyrene-b-poly(ethylene oxide) (PS-PEO) diblock copolymers, by in situ micropipette tensiometry on evaporating emulsion drops. These measurements suggest that the sensitivity to the organic solvent chosen reflects both differences in the bare solvent/water interfacial tension as well as the propensity of the copolymer to aggregate within the organic phase. While instabilities coincident with an approach of the interfacial tension nearly to zero were observed only for copolymers with PEO content greater than 15 wt.%, beyond this point the interfacial behavior and critical concentration needed to trigger surface instability were found to depend only weakly on copolymer composition. PMID- 21981971 TI - Enhanced surface segregation of poly(methyl methacrylate) end-capped with 2 perfluorooctylethyl methacrylate by introduction of a second block. AB - New fluorinated copolymers of poly(methyl methacrylate)-b-poly(butyl methacrylate) or poly(n-octadecyl methacrylate) end-capped with 2 perfluorooctylethyl methacrylate (PMMA(x)-b-PBMA(y)-ec-PFMA(z) or PMMA(x)-b PODMA(y)-ec-PFMA(z)) were synthesized by living atom transfer radical polymerization. Thin films made of PMMA(230)-b-PODMA(y)-ec-PFMA(1) were characterized by differential scanning calorimetry, angle-resolved X-ray photoelectron spectroscopy and X-ray diffraction. These films were found to exhibit robust surface segregation of the end groups. Furthermore, the fluorine enrichment factor at the film surface was found to increase linearly with increasing degree of polymerization of poly(n-octadecyl methacrylate) and its increasing fusion enthalpy in the second block, which enhances the segregation of the fluorinated moieties. PMID- 21981972 TI - Short timescale inkjet ink component diffusion: an active part of the absorption mechanism into inkjet coatings. AB - The structures of inkjet coatings commonly contain a high concentration of fine diameter pores together with a large pore volume capacity. To clarify the interactive role of the porous structure and the coincidentally occurring swelling of binder during inkjet ink vehicle imbibition, coating structures were studied in respect to their absorption behaviour for polar and non-polar liquid. The absorption measurement was performed using compressed pigment tablets, based on a range of pigment types and surface charge polarity, containing either polyvinyl alcohol (PVOH) or styrene acrylic latex (SA) as the binder, by recording the liquid uptake with a microbalance. The results indicate that, at the beginning of liquid uptake, at times less than 2 s, the small pores play the dominant role with respect to the inkjet ink vehicle imbibition. Simultaneously, water molecules diffuse into and within the hydrophilic PVOH binder causing binder swelling, which diminishes the number of active small pores and reduces the diameter of remaining pores, thus slowing the capillary flow as a function of time. The SA latex does not absorb the vehicle, and therefore the dominating phenomenon is then capillary absorption. However, the diffusion coefficient of the water vapour across separately prepared PVOH and SA latex films seems to be quite similar. In the PVOH, the polar liquid diffuses into the polymer network, whereas in the SA latex the hydrophobic nature prevents the diffusion into the polymer matrix and there exists surface diffusion. At longer timescale, permeation flow into the porous coating dominates as the resistive term controlling the capillary driven liquid imbibition rate. PMID- 21981968 TI - Impact of caloric and dietary restriction regimens on markers of health and longevity in humans and animals: a summary of available findings. AB - Considerable interest has been shown in the ability of caloric restriction (CR) to improve multiple parameters of health and to extend lifespan. CR is the reduction of caloric intake - typically by 20 - 40% of ad libitum consumption - while maintaining adequate nutrient intake. Several alternatives to CR exist. CR combined with exercise (CE) consists of both decreased caloric intake and increased caloric expenditure. Alternate-day fasting (ADF) consists of two interchanging days; one day, subjects may consume food ad libitum (sometimes equaling twice the normal intake); on the other day, food is reduced or withheld altogether. Dietary restriction (DR) - restriction of one or more components of intake (typically macronutrients) with minimal to no reduction in total caloric intake - is another alternative to CR. Many religions incorporate one or more forms of food restriction. The following religious fasting periods are featured in this review: 1) Islamic Ramadan; 2) the three principal fasting periods of Greek Orthodox Christianity (Nativity, Lent, and the Assumption); and 3) the Biblical-based Daniel Fast. This review provides a summary of the current state of knowledge related to CR and DR. A specific section is provided that illustrates related work pertaining to religious forms of food restriction. Where available, studies involving both humans and animals are presented. The review includes suggestions for future research pertaining to the topics of discussion. PMID- 21981973 TI - Frequency of intensive statin therapy in patients with acute coronary syndrome admitted to a tertiary care center. AB - Intensive statin therapy (IST) has been shown to decrease cardiovascular events in patients with acute coronary syndrome (ACS). Numerous studies have described statin use for secondary prevention; however, few data have highlighted IST use after ACS. The objective of the present study was to describe IST use in an ACS population before hospitalization, on discharge, and during early follow-up after discharge. A retrospective chart review was conducted of randomly selected patients admitted to a tertiary care center from November 1, 2007 to October 31, 2008. Eligible patients included adults admitted to cardiology with a most responsible diagnosis of ACS (International Classification of Diseases code 20 25). The exclusion criteria included transfer to another hospital or cardiovascular surgery ward and in-hospital death. Phase 1 included an inpatient chart review. Phase 2 was a follow-up cardiologist clinic letter review that included only patients who started IST in-hospital. Of 234 charts reviewed, 111 (47%) patients met the inclusion criteria (mean age 65 +/- 11.7 years, 76% men). Most patients (93%) were discharged with a statin. However, although 72% of the study population were eligible for IST, only 52% had IST during hospitalization. Of the patients who started IST with clinic letters available (n = 31), 68% continued IST (mean interval to follow-up 85 days, range 33 to 208). In conclusion, although statin use is good, IST use after ACS is suboptimal. Additionally, newly initiated IST demonstrates poor persistence after discharge. PMID- 21981974 TI - PHGDH amplification and altered glucose metabolism in human melanoma. AB - The metabolic requirements of cancer cells differ from that of their normal counterparts. To support their proliferation, cancer cells switch to a fermentative metabolism that is thought to support biomass production. Instances where metabolic enzymes promote tumorigenesis remain rare. However, an enzyme involved in the de novo synthesis of serine, 3-phosphoglycerate dehydrogenase (PHGDH), was recently identified as a putative oncogene. The potential mechanisms by which PHGDH promotes cancer are discussed. PMID- 21981975 TI - [Orthodontic anchorage]. AB - INTRODUCTION: Orthodontic treatments apply forces on teeth to move them. Since there is no fixed anatomic anchorage, every orthodontic action will cause a counter-action of equal force. This is usually unwanted and strong bone anchorage is used to prevent this counter-action. These anchorages provide the fixed point required for orthodontic effectiveness. TECHNIQUE: We describe some devices, their implantation site, placement, and removal. Our experience is essentially based on the Lomas(r) and Orthocorrect(r) devices manufactured by Mondeal(r) (Germany) and on screwed anchorage devices manufactured by Stryker(r) (USA). DISCUSSION: These screwed anchorage systems allow for previously impossible treatments, especially for orthodontics applied to adults and for preprosthetic orthodontics. But these screws can induce apical migration of teeth; so it may be necessary to provide several anchorage sites. Complications are rare and usually present as root perforation. PMID- 21981976 TI - [Cone beam 3D sialography: preliminary study]. AB - INTRODUCTION: Stones, stenosis and inflammatory lesions are the main causes of mealtime syndrome. The aim of paraclinical exam is to find the cause of these obstructive symptoms. Ultrasound is often sufficient to confirm the lithiasic origin of salivary gland swelling. Non-lithiasic salivary obstructions are more difficult to diagnose. We studied the feasibility and quality of a new medical imaging device: three-dimensional (3D) sialography using the technique of cone beam with flat panel (CPCT). PATIENTS AND METHODS: Five patients were included, referred for diagnostic management of non-lithiasic salivary gland parotid colic. It was performed for each patient in the angiography room, conventional sialography and 3D CPCT. Images were compared to conventional sialography. RESULTS: None of catheterization failure or side effects were observed in five patients. 3D CPCT sialography enabled to view gland ducts until their fifth or sixth division. Compared to conventional sialography, 3D CPCT improves signal and contrast to noise ratio. DISCUSSION: This technique allows an anatomic resolution and signal/noise ratio unmatched. It also allows to reduce metallics artefacts. Its main drawback is those associated with ductal catheterization, exposure to ionizing radiation and potential allergy to iodinated contrast agents. PMID- 21981977 TI - [Hydatid cyst of the thyroid in a child]. AB - INTRODUCTION: Hydatidosis is an anthropozoonosis due to the development of the Echinococcus granulosus in humans. Thyroid gland involvement is rather rare. The authors report a very rare case of thyroid gland hydatidosis in a child. OBSERVATION: A 6-year-old male child presented with an isolated neck mass. Cervical ultrasonography suggested a cystic thyroid nodule. No invasive investigation was performed. Hepatic ultrasound and chest radiography were normal. Hydatid serology was negative. The tumor was en-bloc removed by cervicotomy. Its content was fluid, crystal clear, with membranes confirming the hydatid origin. There was no recurrence after 9 months. DISCUSSION: Even though hydatidosis in the thyroid is rare, it should be considered in case of anterior cervical tumor, for patients living in endemic zones. The only radical treatment is surgery. An en-bloc resection must be performed with a cystectomy, isthmolobectomy, or total thyroidectomy. PMID- 21981978 TI - ["Double barrel" free fibula flap and vascular risk. A national investigation in France]. AB - INTRODUCTION: The free fibula flap is the most commonly used flap for mandibular reconstruction thanks to its multiple advantages. Its main drawback is the thin width of the bone section. The "double barrel" fibula flap is a solution to this problem allowing reconstruction of both basilar and alveolar ridges for a stable prosthetic dental rehabilitation. The authors wanted to assess its use, in France, to evaluate its reliability, and to determine its indications. PATIENTS AND METHODS: The authors sent a questionnaire to the 25 French Maxillo-Facial University Hospital Departments. Questions concerned the surgical technique, its indications, and the operative results, between January 2002 and December 2007. RESULTS: Out of the 18 teams who answered, 16 used a free fibula flap for mandibular reconstruction but only seven used the double barrel technique, for a total of 24 double barrel reconstructions. Only one total necrosis was reported. The indications for double barrel fibula flap were nearly all for corpus reconstruction and the operating overtime was less than one hour. DISCUSSION: The international literature review analysis gives results which compare to French ones, with a weak rate of necrosis despite the intermediate rectangular ostectomy. This technique may be recommended especially since it does not increase the operative time much and it improves dental restoration. PMID- 21981979 TI - Prevalence and risk factors of helminths and intestinal protozoa infections among children from primary schools in western Tajikistan. AB - BACKGROUND: Intestinal parasitic infections represent a public health problem in Tajikistan, but epidemiological evidence is scarce. The present study aimed at assessing the extent of helminths and intestinal protozoa infections among children of 10 schools in four districts of Tajikistan, and to make recommendations for control. METHODS: A cross-sectional survey was carried out in early 2009. All children attending grades 2 and 3 (age: 7-11 years) from 10 randomly selected schools were invited to provide a stool sample and interviewed about sanitary situation and hygiene behaviour. A questionnaire pertaining to demographic and socioeconomic characteristics was addressed to the heads of households. On the spot, stool samples were subjected to duplicate Kato-Katz thick smear examination for helminth diagnosis. Additionally, 1-2 g of stool was fixed in sodium acetate-acetic acid-formalin, transferred to a specialised laboratory in Europe and examined for helminths and intestinal protozoa. The composite results from both methods served as diagnostic 'gold' standard. RESULTS: Out of 623 registered children, 602 participated in our survey. The overall prevalence of infection with helminths and pathogenic intestinal protozoa was 32.0% and 47.1%, respectively. There was pronounced spatial heterogeneity. The most common helminth species was Hymenolepis nana (25.8%), whereas the prevalences of Ascaris lumbricoides, hookworm and Enterobius vermicularis were below 5%. The prevalence of pathogenic intestinal protozoa, namely Giardia intestinalis and Entamoeba histolytica/E. dispar was 26.4% and 25.9%, respectively. Almost half of the households draw drinking water from unimproved sources, such as irrigation canals, rivers and unprotected wells. Sanitary facilities were pit latrines, mostly private, and a few shared with neighbours. The use of public tap/standpipe as a source of drinking water emerged as a protective factor for G. intestinalis infection. Protected spring water reduced the risk of infection with E. histolytica/E. dispar and H. nana. CONCLUSIONS: Our data obtained from the ecological 'lowland' areas in Tajikistan call for school based deworming (recommended drugs: albendazole and metronidazole), combined with hygiene promotion and improved sanitation. Further investigations are needed to determine whether H. nana represents a public health problem. PMID- 21981980 TI - 1,3-Dihydro-2H-indol-2-ones derivatives: design, synthesis, in vitro antibacterial, antifungal and antitubercular study. AB - 1,3-dihydro-2H-indol-2-ones derivatives are reported to exhibit a wide variety of biodynamic activities such as antituberculer, anti HIV, fungicidal, antibacterial, anticonvulsant. These valid observations led us to synthesize some new indole-2-one derivative. Thus, herein we report synthesis of various 5 substituted-3-[{5-(6-methyl-2-oxo/thioxo-4-phenyl-1,2,3,4 tetrahydro pyrimidin-5 yl)-1,3,4-thiadiazol-2-yl}imino]-1,3-dihydro-2H-indol-2-one derivatives 4a-l using one pot multicomponent-Biginelli reaction via CaCl(2) catalyst. Structures and purity of these compounds were confirmed by elemental, IR, ((1)H &(13)C) NMR and Mass spectral analysis. Newly synthesized compounds were also tested for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H(37)Rv, in vitro antibacterial activity against selected human pathogens viz. Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Staphylococcus aureus, Staphylococcus pyogenus, Bacillus subtilis and antifungal activity against Candida albicans, Aspergillus niger, Aspergillus clavatus strains. PMID- 21981981 TI - Synthesis, biological assay in vitro and molecular docking studies of new Schiff base derivatives as potential urease inhibitors. AB - A series of new and novel Schiff base derivatives were synthesized and investigated as potential new inhibitors of Jack bean urease. The most potent compounds were 3f with (K(i) = 0.09 MUM) and 3k (K(i) = 0.122 MUM). A pure competitive mechanism of inhibition was observed. Molecular docking studies were also performed to illustrate the binding mode of the compounds. Docking studies were performed on both enzymes from Jack bean urease and H. pylori urease. It was observed that both share the same binding mode. The binding sites of the two urease structures also aligned very well indicating the similarity in binding sites of the enzymes. PMID- 21981982 TI - High ambient temperature and mortality in California: exploring the roles of age, disease, and mortality displacement. AB - Investigators have consistently demonstrated associations between elevated temperatures and mortality worldwide. Few have recently focused on identifying vulnerable subgroups, and far fewer have determined whether at least some of the observed effect may be a manifestation of mortality displacement. We examined mean daily apparent temperature and mortality in 13 counties in California during the warm season from 1999 to 2006 to identify age and disease subgroups that are at increased risk, and to evaluate the potential effect of mortality displacement. The time-series method using the Poisson regression was applied for data analysis for single lag days of 0-20 days, and for cumulative average lag days of five and ten days. Significant associations were observed for the same day (excess risk=4.3% per 5.6 degrees C increase in apparent temperature, 95% confidence interval: 3.4, 5.2) continuing up to a maximum of three days following apparent temperature exposure for non-accidental mortality. Similar risks were found for mortality from cardiovascular diseases, respiratory diseases, and among children zero to 18 years of age, and adults and the elderly 50 years and older. Since no significant negative effects were observed in the following single or cumulative days, evidence of mortality displacement was not found. Thus, the effect of temperature on mortality appears to be an event that occurs within three days following exposure, and requires immediate attention for prevention. PMID- 21981983 TI - Evaluation of an alternative HIV diagnostic algorithm using specimens from seroconversion panels and persons with established HIV infections. AB - BACKGROUND: The current algorithm for HIV diagnosis in the US involves screening with an immunoassay (IA) and supplemental testing with Western blot (WB) or immunofluorescence assay. Because of existence of more sensitive and specific FDA approved assays that would also reduce the cost and turn-around time of testing compared to WB, several alternative algorithms have been evaluated. Recently, an alternative algorithm using a sensitive 3rd or 4th generation IA followed by an HIV-1 and HIV-2 discriminatory supplemental test on the initial IA-positive specimens was proposed. Concordant positive results indicate HIV-positive specimens and discordant results are resolved by nucleic acid amplification testing (NAAT). OBJECTIVES: To evaluate the sensitivity of assays during acute HIV infection and the performance of the current and an alternative algorithm using samples from HIV-1 seroconversion panels and persons with established HIV infections. STUDY DESIGN: To evaluate the algorithms in early infections, 26 HIV 1 seroconverters from the US were tested with three 3rd generation and one 4th generation IA, six rapid tests (RTs), one NAAT, and WB. Sensitivity and specificity of the algorithms were calculated by testing an additional 416 HIV positive and 414 uninfected control samples with one 3rd generation and one 4th generation IA, four RTs, one NAAT, and WB. RESULTS: The individual assays evaluated became positive 5 (RT) to 26 days (NAAT) before WB was positive. Among seroconverters, the alternative algorithm detected significantly more infections than the current algorithm (103-134 versus 56, p<0.0001). Furthermore, the use of a 4th generation IA instead of a 3rd generation assay as the screen resulted in significantly higher detection of acute infections (p<0.0001). In contrast, the algorithms performed equally among specimens from established HIV-1 infections. CONCLUSIONS: This study demonstrated improved sensitivity of the alternative algorithm for detecting acute HIV-1 infections, while maintaining the ability to accurately detect established HIV-1 infections. Early detection is important as individuals can be highly infectious during acute infection. In addition, the alternative algorithm should reduce turn-around time by using a RT as the supplemental test has the potential to increase the number of test results returned. PMID- 21981984 TI - Complex total knee arthroplasty using resection prostheses at mid-term follow-up. AB - Complex primary or revision TKA may require the use of a resection type prosthesis to address major bone loss and soft tissue deficiencies. The aim of this retrospective study is to evaluate the clinical and radiographic outcomes of salvage knee reconstructions in a larger cohort and longer follow-up than previously reported. We therefore present the results of 66 cases treated with the Finn/OSS knee system with an average follow-up of 5 years (range 2-12). Indications included 63 revision cases and three primary interventions with either massive bone loss and/or soft tissue deficiency. At final follow-up the average knee society score had significantly improved from 46 preoperatively to 73, and the function score improved from 27 to 47 points. Four cases needed to be revised: one for recurrent infection, two for aseptic loosening and one for implant breakage. Nine patients underwent minor reinterventions; including five cases with irrigation and debridement for prolonged wound drainage, two patellar realignment procedures and two extensor mechanism repairs. Two patients developed a peroneal nerve palsy. Overall implant survivorship with revision as the endpoint was 92% at 5 and 10 years. We conclude that the use of a resection prosthesis in the complex primary and revision TKA leads to acceptable results, but the complication rate is relatively high. PMID- 21981985 TI - PADI4 polymorphisms and related haplotype in rheumatoid arthritis patients. AB - OBJECTIVE: To investigate whether peptidyl arginine deiminase type IV gene (PADI4) polymorphisms contribute to rheumatoid arthritis (RA) susceptibility in Egyptians, whether they influence disease severity and activity, and whether they affect anti-mutated citrullinated vimentin antibodies (anti-MCV) level. METHODS: Three PADI4 single nucleotide polymorphisms (SNPs) (PADI4-92, PADI4-96, and PADI4 102) were screened in 275 RA patients and 275 unaffected controls by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method. Serum anti-MCV levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: There were significant associations between RA susceptibility with the minor alleles of PADI4-92 and PADI4-102 [odds ratio (OD) and 95% confidence interval (CI) for the minor alleles of PADI4-92 and PADI4-102: 1.48 (1.17-1.88) and 2.05 (1.61-2.61) respectively] but not with PADI4-96 [OD and 95% CI for the C allele: 1.09 (0.86-1.39)]. PADI4 haplotypes 2 (GCC) and 3 (GCT) were also associated with RA susceptibility while PADI4 haplotypes 1 (CTC) may be protective against developing of this disease. A significant association was detected between PADI4 haplotypes and RA severity. CONCLUSIONS: The PADI4 SNPs and haplotypes were associated with RA susceptibility, although no relation was observed between the PADI4 haplotypes and anti-MCV levels. PMID- 21981986 TI - A comparison of complementary and alternative medicine users and use across geographical areas: a national survey of 1,427 women. AB - BACKGROUND: Evidence indicates that people who reside in non-urban areas have a higher use of complementary and alternative medicine (CAM) than people who reside in urban areas. However, there is sparse research on the reasons for such differences. This paper investigates the reasons for geographical differences in CAM use by comparing CAM users from four geographical areas (major cities, inner regional, outer region, rural/remote) across a range of health status, healthcare satisfaction, neighbourhood and community factors. METHODS: A cross-sectional survey of 1,427 participants from the Australian Longitudinal Study on Women's Health (ALSWH) conducted in 2009. RESULTS: The average total cost of consultations with CAM practitioners was $416 per annum and was highest for women in the major cities, declining with increasing distance from capital cities/remoteness (p < 0.001). The average total cost of self-prescribed CAM was $349 per annum, but this did not significantly differ across geographical areas. The increased use of CAM in rural and remote areas appears to be influenced by poorer access to conventional medical care (p < 0.05) and a greater sense of community (p < 0.05) amongst these rural and remote residents. In contrast to the findings of previous research this study found that health status was not associated with the differences in CAM use between urban and non-urban areas. CONCLUSION: It appears that a number of factors influence the different levels of CAM use across the urban/non-urban divide. Further research is needed to help tease out and understand these factors. Such research will help support health care policy and practice with regards to this topic. PMID- 21981987 TI - Oxford unicompartmental knee arthroplasty: medial pain and functional outcome in the medium term. AB - BACKGROUND: In our experience results of the Oxford unicompartmental knee replacement have not been as good as had been expected. A common post operative complaint is of persistent medial knee discomfort, it is not clear why this phenomenon occurs and we have attempted to address this in our study. METHODS: 48 patients were retrospectively identified at a mean of 4.5 years (range = 3 to 6 years) following consecutive Oxford medial Unicompartmental Knee arthroplasties for varus anteromedial osteoarthritis. The mean age at implantation was 67 years (range 57-86). Of these 48 patients, 4 had died, 4 had undergone revision of their unicompartmental knee replacements and 2 had been lost to follow up leaving 38 patients with 40 replaced knees available for analysis using the 'new Oxford Knee Score' questionnaire. During assessment patients were asked specifically whether or not they still experienced medial knee discomfort or pain. RESULTS: The mean 'Oxford score' was only 32.7 (range = 16 to 48) and 22 of the 40 knees were uncomfortable or painful medially.The accuracy of component positioning was recorded, using standard post operative xrays, by summing the angulation or displacement of each component in two planes from the ideal position (according to the 'Oxford knee system radiographic criteria'). No correlation was demonstrated between the radiographic scores and the 'Oxford scores', or with the presence or absence of medial knee discomfort or pain. CONCLUSION: In our hands the functional outcome following Oxford Unicompartmental knee replacement was variable, with a high incidence of medial knee discomfort which did not correlate with the postoperative radiographic scores, pre-op arthritis and positioning of the prosthesis. PMID- 21981988 TI - Prevalence of peripheral arterial disease in subjects with moderate cardiovascular risk: Italian results from the PANDORA study Data from PANDORA (Prevalence of peripheral Arterial disease in subjects with moderate CVD risk, with No overt vascular Diseases nor Diabetes mellitus). AB - BACKGROUND: The PANDORA study has recently examined the prevalence of low ankle brachial index (ABI) in subjects with moderate risk of cardiovascular disease. This sub-analysis of the PANDORA study examines the prevalence of asymptomatic peripheral arterial disease (PAD), as determined by ABI, in Italian subjects presenting with moderate cardiovascular risk, in the absence of diabetes or overt vascular disease. METHODS: PANDORA is a non-interventional, cross-sectional study that was performed in 6 European countries, involving subjects with at least one cardiovascular (CV) risk factor. The primary objective was to evaluate the prevalence of asymptomatic PAD using ABI. For this post-hoc sub-analysis, data were extracted for subjects enrolled in Italy, comprising 51.5% (n = 5298) of subjects from the original PANDORA study. Secondary objectives were to establish the prevalence and treatment of CV risk factors. RESULTS: The mean age was 63.9 years and 22.9% (95% CI 21.7-24.0) of subjects presented with asymptomatic PAD. A range of risk factors comprising smoking, hypertension, low HDL-cholesterol, family history of coronary heart disease and habit of moderate-high alcohol intake were significantly associated with asymptomatic PAD (p < 0.0001). Statin treatment had the lowest incidence in Italian subjects. Furthermore, patients treated with statins were significantly less likely to have asymptomatic PAD than those who were not (p = 0.0001). CONCLUSIONS: Asymptomatic PAD was highly prevalent in Italian subjects, the majority of whom were not candidates for ABI assessment according to current guidelines. Findings from this study suggest that these patients should be carefully examined in clinical practice and ABI measured so that therapeutic interventions known to decrease their CV risk may be offered. PMID- 21981989 TI - Traffic-related air toxics and preterm birth: a population-based case-control study in Los Angeles County, California. AB - BACKGROUND: Numerous studies have associated air pollutant exposures with adverse birth outcomes, but there is still relatively little information to attribute effects to specific emission sources or air toxics. We used three exposure data sources to examine risks of preterm birth in Los Angeles women when exposed to high levels of traffic-related air pollutants--including specific toxics--during pregnancy. METHODS: We identified births during 6/1/04-3/31/06 to women residing within five miles of a Southern California Air Quality Management District (SCAQMD) Multiple Air Toxics Exposure Study (MATES III) monitoring station. We identified preterm cases and, using a risk set approach, matched cases to controls based on gestational age at birth. Pregnancy period exposure averages were estimated for a number of air toxics including polycyclic aromatic hydrocarbons (PAHs), source-specific PM2.5 (fine particulates with aerodynamic diameter less than 2.5 MUm) based on a Chemical Mass Balance model, criteria air pollutants based on government monitoring data, and land use regression (LUR) estimates of nitric oxide (NO), nitrogen dioxide (NO2) and nitrogen oxides (NOx). Associations between these metrics and odds of preterm birth were estimated using conditional logistic regression. RESULTS: Odds of preterm birth increased 6-21% per inter-quartile range increase in entire pregnancy exposures to organic carbon (OC), elemental carbon (EC), benzene, and diesel, biomass burning and ammonium nitrate PM2.5, and 30% per inter-quartile increase in PAHs; these pollutants were positively correlated and clustered together in a factor analysis. Associations with LUR exposure metrics were weaker (3-4% per inter-quartile range increase). CONCLUSIONS: These latest analyses provide additional evidence of traffic-related air pollution's impact on preterm birth for women living in Southern California and indicate PAHs as a pollutant of concern that should be a focus of future studies. Other PAH sources besides traffic were also associated with higher odds of preterm birth, as was ammonium nitrate PM2.5, the latter suggesting potential importance of secondary pollutants. Future studies should focus on accurate modeling of both local and regional spatial and temporal distributions, and incorporation of source information. PMID- 21981992 TI - Molecular differentiation of Entamoeba spp. in a rural community of Loja province, South Ecuador. AB - Although previous epidemiological surveys in Ecuador indicate the presence of Entamoeba histolytica, prevalence data of this parasite remain scarce. Most of the studies were based on microscopic examination, which does not allow a morphological differentiation from the non-pathogenic Ent. dispar and Ent. moshkovskii. In the present study, 674 stool samples from a South Ecuadorian rural community were screened for Entamoeba spp. Subsequently, molecular identification was performed on 101 samples containing Ent. histolytica/Ent. dispar/Ent. moshkovskii cysts. The study indicated the absence of Ent. histolytica in this South Ecuadorian community and confirmed the difficulty of differentiating Entamoeba spp. based on morphological features. PMID- 21981991 TI - Contingency management delivered by community therapists in outpatient settings. AB - BACKGROUND: Few community-based clinicians have been trained to deliver contingency management (CM) treatments, and little data exist regarding the efficacy of CM when administered by clinicians. METHOD: Fifteen clinicians from four intensive outpatient treatment programs received training in CM. Following a didactics seminar and a period in which clinicians delivered CM to pilot patients while receiving weekly supervision, clinicians treated 43 patients randomized to standard care or CM, without supervision. In both treatment conditions, urine and breath samples were collected up to twice weekly for 12 weeks, and CM patients earned the opportunity to win prizes ranging in value from $1 to $100 for submitting drug-free samples. Primary treatment outcomes were sessions attended, unexcused absences, longest continuous period of abstinence, and proportion of negative samples submitted. RESULTS: All therapists completed the training and supervision phase, and 10 treated randomized patients. Patients randomized to CM achieved significantly greater durations of abstinence than patients randomized to standard care (5.0+/-3.8 weeks versus 2.6+/-3.7 weeks) and had fewer unexcused absences (4.3+/-1.2 versus 8.1+/-5.4), but proportion of negative samples submitted and attendance did not differ significantly between groups. Therapist adherence and competence in CM delivery decreased when supervision was no longer provided, and competence in CM delivery was associated with duration of abstinence achieved and attendance. CONCLUSIONS: Community-based clinicians can effectively administer CM, and outcomes relate to competence in CM delivery. These data call for further training and supervision of community clinicians in this evidence-based treatment. PMID- 21981990 TI - Child maltreatment increases sensitivity to adverse social contexts: neighborhood physical disorder and incident binge drinking in Detroit. AB - INTRODUCTION: Exposure to child maltreatment is associated with elevated risk for behavioral disorders in adulthood. One explanation for this life-course association is that child maltreatment increases vulnerability to the effects of subsequent stressors; however, the extent to which maltreatment increases sensitivity to social context has never been examined. We evaluated whether the association between neighborhood physical disorder and binge drinking was modified by child maltreatment exposure. METHODS: Data were drawn from the Detroit Neighborhood Health Study, a prospective representative sample of predominately African Americans in the Detroit population. Neighborhood physical disorder was measured via systematic neighborhood assessment. Child maltreatment indicators included self-reported physical, sexual, and emotional abuse. Incident binge drinking was defined as at least one episode of >=5 drinks (men) or >=4 drinks (women) in the past 30-day period among those with no binge drinking at baseline (N=1013). RESULTS: Child maltreatment and neighborhood physical disorder interacted to predict incident binge drinking (B=0.16, p=0.02) and maximum number of past 30-day drinks (B=0.15, p=0.04), such that neighborhood physical disorder predicted problematic alcohol use only among individuals with high exposure to child maltreatment. CONCLUSION: The results add to the growing literature that African Americans in the US are exposed to an array of stressors that have pernicious consequences for problematic alcohol use. Our results document the need for increased attention to the potential for at-risk alcohol use among populations with a high degree of stress exposure. PMID- 21981994 TI - Case studies emphasising the difficulties in the diagnosis and management of alveolar echinococcosis in rural China. AB - BACKGROUND: Human alveolar echinococcosis (AE) is caused by the accidental ingestion of the eggs of the fox tapeworm Echinococcus multilocularis. AE occurs frequently in rural western China due to the poor levels of hygiene, the close contact of people with dogs, and the lack of appropriate facilities for the correct and rapid diagnosis of the disease. FINDINGS: We describe a case of a patient with hepatic AE, and AE metastases of the brain. She was mistakenly diagnosed with suspected undifferentiated metastatic cancer of the liver and brain, and with a pulmonary bacterial infection, but was subsequently correctly diagnosed during a follow-up field survey for echinococcosis. The diagnosis of brain AE was confirmed by pathological examination of tissue biopsies removed during neurosurgery. We also briefly describe other symptomatic and asymptomatic AE cases, identified by chance, likely due to the inadequate facilities available in rural communities in China for AE diagnosis and management, since the rapid and accurate diagnosis of metastatic AE requires a high level of expertise in the appropriate diagnostic procedures. CONCLUSIONS: This report highlights the necessity for an upgrade in the diagnosis, treatment, prevention and control of AE in rural China. PMID- 21981993 TI - Inhibition of coding region determinant binding protein sensitizes melanoma cells to chemotherapeutic agents. AB - We previously reported that malignant melanomas express high levels of the mRNA binding protein coding region determinant binding protein (CRD-BP). This molecule is important for the activation of anti-apoptotic pathways, a mechanism often linked to insensitivity to therapeutics. However, it is not known whether CRD-BP plays a role in the resistance of melanomas to anti-cancer treatment. Here we demonstrate that knockdown of CRD-BP with a specific sh-RNA enhances the effect of dacarbazine, temozolomide, vinblastine, and etoposide on both primary and metastatic melanoma cell lines. CRD-BP down-regulation contributes to cell sensitization by increasing apoptosis and diminishing melanoma cell growth in response to chemotherapeutic agents. Furthermore, inhibition of CRD-BP decreases microphthalmia-associated transcription factor (MITF) expression and reintroduction of MITF partially compensates for the absence of CRD-BP. These findings suggest that high expression of CRD-BP in melanoma cells confers resistance to chemotherapy and that these CRD-BP responses are mediated, at least in part, by MITF. PMID- 21981995 TI - Molecular cloning of bovine lymphocyte activation gene-3 and its expression characteristics in bovine leukemia virus-infected cattle. AB - Lymphocyte activation gene-3 (LAG-3), a major histocompatibility complex (MHC) class II binding CD4 homologue has recently been shown as one of the mechanisms for down-regulating immune responses during chronic disease progression. For the first time, we cloned LAG-3 from two breeds of cattle (Holstein and Japanese Black), and analyzed its expression levels in cattle infected with bovine leukemia virus (BLV), a chronic viral infection that leads to immuno-suppression. The cloned cDNA of bovine LAG-3 have an open reading frame of 1551 nucleotides, encoding a polypeptide of 515 amino acids in length. Similar to the swine LAG-3, the bovine LAG-3 protein sequence consisted of four extracellular domains, a transmembrane domain and an inhibitory motif, KTGELE. We found that the bovine LAG-3 mRNA transcripts were expressed predominantly on T-cells such as CD4(+) and CD8(+) cells, among peripheral blood mononuclear cells. In subsequent expression analysis, LAG-3 mRNA expression on CD4(+) T-cells from BLV-infected cattle was upregulated compared to that in normal cattle. Comparable results were obtained with CD8(+) T-cells from cattle infected with BLV. We further observed strong upregualtion of MHC class II molecule, the ligand for LAG-3 in BLV-infected cattle. These findings indicate an important role for inhibitory receptor molecules such as LAG-3 in chronic bovine infections and future studies will elucidate the specific role of LAG-3 in bovine diseases. PMID- 21981996 TI - The impact of oral versus inhaled glucocorticoids on allergen specific IgE testing in experimentally asthmatic cats. AB - Glucocorticoids (GCs) are palliative for allergic asthma, but allergen-specific immunotherapy (ASIT), which relies on identification of allergens, represents a potentially curative treatment. The purpose of this study was to determine if oral or inhaled GCs would interfere with identification of sensitizing allergens. The hypothesis was that oral but not inhaled GCs would interfere with accurate allergen-specific IgE identification determined by skin and serum testing in experimentally asthmatic cats. Asthma was induced in 18 cats using Bermuda grass allergen (BGA). Cats (n=6/group) were randomized to receive oral GCs (10mg prednisolone q 24 h), inhaled GCs (600 MUg budesonide q 24 h) or placebo (q 24 h PO) for one month. Intradermal skin testing (IDST) and serum BGA-specific IgE were measured prior to, during and after treatment. A paired t test was used to compare groups pre- and post-treatment (P<0.05 significant). IDST reactivity was eliminated in 4/6, 3/6, and 1/6 cats receiving oral GCs, inhaled GCs, and placebo respectively. Two weeks after stopping treatment, IDST was again positive in all cats. Serum IgE reactivity to BGA was not significantly diminished by any treatment. In conclusion, a two-week withdrawal from GCs is adequate for IDST, but may not be necessary for serum IgE testing. PMID- 21981997 TI - Characterization of antibodies specific for canine TLR4, 5 and 9 by ELISA, Western blotting and immunohistochemistry. AB - Toll-like receptors recognize pathogen-associated molecular patterns of microbial origin, and ligand recognition results in the production of different immune mediators such as pro-inflammatory cytokines, interferon, reactive oxygen and nitrogen intermediates, and upregulation of costimmulatory molecules. As these receptors have a critical role in linking pathogen recognition to induction of inflammation and innate as well as adaptive immunity, there is tremendous interest in understanding how the tissue and cell-type expression of TLRs is regulated and its influence on the local innate immune response. While TLRs are well studied in humans and rodents, to date little is known about them in dogs. The purpose of this study was to develop canine specific antibodies against TLR2, 4, 5 and 9 that were used to measure relative expression of these TLRs in healthy and reactive canine mesenteric lymph nodes. All 8 rabbit sera (2 each for TLR2, 4, 5 and 9) were strongly positive in ELISA against the respective 2 peptides per TLR used for immunization. The purified antibodies selected specifically detected a protein band with an apparent size of approximately 70 kDa in lysates of canine PBMCs by Western blotting. Immunostaining was observed with purified antibodies against TLR4, 5 and 9, whereas for canine TLR2, staining was only observed with the unpurified antibodies. In the mesenteric lymph node of healthy dogs, the overall staining pattern was very similar for TLR4 and 5 with positive cells predominantly found in the internodular areas and lower part of the cortex. Compared to the TLR4 and 5, more cells stained positive for TLR9 especially in the lymphoid nodules. The reactive lymph nodes contained more TLR4 and 9 positive cells. Moreover, a shift of TLR-9 positive cells from the lymphoid follicles to the deep cortex and medullary cords was observed. Whereas TLR9 co-localized with CD79-positive areas, TLR4 and 5 antibodies stained cells primarily in the CD3 positive areas. All three TLR antibodies stained cells within the area that co localized with lysozyme-positive cells. In conclusion, this study demonstrates that the antibodies generated against canine TLR 4, 5 and 9 identify the expression of these TLRs in formalin-fixed canine lymph nodes and demonstrate increased expression in reactive canine mesenteric lymph nodes. PMID- 21981999 TI - Editorial comment. PMID- 21982000 TI - Editorial comment. PMID- 21982001 TI - Editorial comment. PMID- 21982002 TI - Editorial comment. PMID- 21982003 TI - Editorial comment. PMID- 21982004 TI - Editorial comment. PMID- 21982005 TI - Editorial comment. PMID- 21982006 TI - Editorial comment. PMID- 21982008 TI - Editorial comment. PMID- 21982009 TI - Editorial comment. PMID- 21982010 TI - Editorial comment. PMID- 21982012 TI - Editorial comment. PMID- 21982015 TI - Editorial comment. PMID- 21982016 TI - Construction and evaluation of urinary bladder bioreactor for urologic tissue engineering purposes. AB - OBJECTIVE: To design and construct a urinary bladder bioreactor for urologic tissue-engineering purposes and to compare the viability and proliferative activity of cell-seeded extracellular matrix scaffolds cultured in the bioreactor with conventional static growth conditions. MATERIALS AND METHODS: A urinary bladder bioreactor was designed and constructed to replicate physiologic bladder dynamics. The bioreactor mimicked the filling pressures of the human bladder by way of a cyclical low-delivery pressure regulator. In addition, cell growth was evaluated by culturing human urothelial cells (UCs) on porcine extracellular matrix scaffolds in the bioreactor and in static growth conditions for 5 consecutive days. The attachment, viability, and proliferative potential were assessed and compared with quantitative viability indicators and by fluorescent markers for intracellular esterase activity and plasma membrane integrity. Scaffold integrity was characterized with scanning electron microscopy and 4',6 diamidino-2-phenylindole staining. RESULTS: No significant difference in cell viability was identified between both experimental groups after 3 days of culture (P = .06). By day 4, the number of viable UCs was significantly greater in the bioreactor compared with the number cultured under static conditions (P = .009). A significant difference in UC viability was also present after 5 days of culture between the bioreactor and static group (P = .006). Viability/cytotoxicity assays performed on day 5 also confirmed the viability of UCs in both experimental groups. CONCLUSION: Significantly greater UC growth occurred on the extracellular matrix scaffolds cultured in the bioreactor compared with conventional static laboratory conditions after 3 days of culture. Our initial bioreactor prototype might be helpful for permitting additional advances in urinary bladder bioreactor technology. PMID- 21982017 TI - Effects of prolonged vaginal distension and beta-aminopropionitrile on urinary continence and urethral structure. AB - OBJECTIVE: To investigate the effects of prolonged vaginal distension and beta aminopropionitrile (BAPN) on the urinary patterns and urethral structure in female virgin rats. METHODS: A total of 21 female virgin rats were randomly divided into 3 groups of 7 rats each. The control group received no intervention; the vaginal distension (VD) group was treated with prolonged VD by balloon inflation; and the VD plus BAPN group was treated with VD plus intraperitoneal injection of 150 mg/kg of BAPN every 3 days. Three weeks later, all the rats underwent conscious cystometric analysis and were then killed for histologic analysis of the urethra. RESULTS: Conscious cystometry identified 0, 3, and 5 rats in the control, VD, and VD plus BAPN groups with an abnormal voiding pattern, respectively. The urethral collagen content was significantly lower in the VD and VD plus BAPN rats compared with the control rats. The urethral elastic fibers were disorganized and shorter in the VD and VD plus BAPN rats and were fragmented and lacking the intermuscle connections in the VD plus BAPN rats. The urethral striated muscle fibers were shorter and more widely spaced in the VD and VD plus BAPN rats than in the control rats. Additionally, those in the VD plus BAPN group exhibited an abnormal wavy shape suggestive of a lack of architectural support. CONCLUSION: Prolonged vaginal distension caused urodynamic changes and histologic abnormalities in the urethra, including reduced collagen content, fragmented elastic fibers, and sparsely arranged and shortened striated muscle fibers. BAPN appears to interfere with the restoration of collagen and elastic fibers. PMID- 21982019 TI - HNF1B polymorphism associated with development of prostate cancer in Korean patients. AB - OBJECTIVE: To identify whether the genetic variations in HNF1B are associated with the development of prostate cancer in Korean patients. Genome-wide association studies have found the HNF1B gene at 17q12 to be a major causal gene for the risk of prostate cancer. METHODS: We evaluated the association of 47 single nucleotide polymorphisms (SNPs) in the HNF1B gene with prostate cancer risk and clinical characteristics (Gleason score and tumor stage) in Korean men (240 case subjects and 223 control subjects) using unconditional logistic regression analysis. RESULTS: Of the 47 SNPs, 14 were associated with prostate cancer risk (P = .002-.02); 9 SNPs were associated with a lower risk of prostate cancer (odds ratio 0.67-0.71, P = .005-.05), and 5 SNPs were associated with a greater risk of disease (odds ratio 1.49-1.51, P = .002-.02). In an analysis involving only patients with prostate cancer, 1 SNP (rs11868513) in the HNF1B gene was more frequent in patients with tumors with a greater stage than in those with a lower tumor stage. Two SNPs (rs4430796 and rs2074429) and 1 haplotype (Block3_ht1) were more frequent in patients with Gleason score of >=7 than in those with Gleason score <6. CONCLUSION: As in studies from other populations, our findings indicate that HNF1B is also associated with prostate cancer risk in the Korean population. PMID- 21982018 TI - Interleukin-6: a potential biomarker of resistance to multitargeted receptor tyrosine kinase inhibitors in castration-resistant prostate cancer. AB - OBJECTIVE: To determine if cellular interleukin-6 production predicts response to tyrosine kinase inhibitors (TKIs). As clinical experience using TKIs in patients with castration-resistant prostate cancer (CRPC) matures, Phase II trials show a heterogeneous response to sunitinib in CRPC patients. Change in serum prostate specific antigen (PSA) level has proven unreliable for prediction of CRPC response to TKIs. Interleukin-6 (IL-6), a critical mediator of prostate cancer pathogenesis, has been shown to rise in patients with disease progression. As such, we investigated whether cellular IL-6 production can predict TKI response in both in vitro and in vivo models. METHODS: IL-6 mRNA levels and protein expression were examined by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Apoptosis was examined using the terminal dUTP nick-end labeling assay. For in vivo studies, a CRPC xenograft model in C.B17/Icr-scid mice was used. RESULTS: PC-3 and DU-145 CRPC cell lines exhibited a heterogeneous response to sunitinib and pazopanib. Dose-dependent reduction of IL-6 was observed in TKI-sensitive DU-145 cells. In contrast, the TKI-resistant PC-3 cells failed to suppress IL-6 secretion. Instead, in the presence of tumor necrosis factor-alpha, IL-6 rose significantly upon administration of TKIs. Findings of in vitro experiments were confirmed in an in vivo mouse model of CRPC. CONCLUSION: Sensitivity of CRPC cells to TKIs is heterogeneous. These findings are consistent with results of recently published Phase II clinical trials using sunitinib in patients with CRPC. A substantial rise in IL-6 occurs both in vitro and in vivo in the presence of TKIs in resistant PC-3 cells but not in TKI-sensitive DU-145 cells. These findings suggest that IL-6 may represent a biomarker for TKI resistance in patients with CRPC. PMID- 21982020 TI - Alpha1-adrenoceptor signaling in the human prostate involves regulation of p38 mitogen-activated protein kinase. AB - OBJECTIVE: To investigate whether 1-adrenoceptor signaling in the human prostate involves regulation of the mitogen-activated protein kinase (MAPK) p38. Although alpha1-adrenoceptors are an important target for therapy of lower urinary tract symptoms in patients with prostate hyperplasia, intracellular signaling by prostate alpha1-adrenoceptors is not sufficiently understood. METHODS: Prostate tissue was obtained from patients undergoing radical prostatectomy. The effect of phenylephrine (10 MUM) on p38 activity was assessed by Western blot analysis with a phospho-specific antibody. Expression of p38 was studied by immunohistochemistry and immunofluorescence staining. The effect of the p38 inhibitor SB 202190 (10 MUM) on phenylephrine-induced contraction was studied in myographic measurements. RESULTS: Stimulation of human prostate tissue with phenylephrine resulted in reduced threonine180/tyrosine182 phosphorylation of p38, indicating deactivation of p38 (P = .039 after 5 minutes). Immunohistochemical staining demonstrated expression of p38 in stromal cells of human prostate tissue. Immunofluorescence staining identified these cells as smooth muscle cells, as p38 colocalized with immunoreactivity for alpha-smooth muscle actin. The p38 inhibitor SB 202190 was without effect on phenylephrine induced contraction. CONCLUSION: Using intact human prostate tissue, we herewith describe a new signal transduction pathway of prostate alpha1-adrenoceptors. In addition to mediating contraction, prostate alpha1-adrenoceptors induce intracellular signaling, which results in deactivation of p38 MAPK. This is not involved in alpha1-adrenergic contraction, and points to alpha1-adrenoceptor functions beyond contraction. PMID- 21982021 TI - Repeat antenatal glucocorticoids for women at risk of preterm birth: a Cochrane Systematic Review. AB - Administration of antenatal glucocorticoids to women at risk of preterm birth has major benefits for infants but the use of repeat dose(s) is controversial. We performed a systematic review of randomized trials, using standard Cochrane methodology, to assess the effectiveness and safety of 1 or more repeat doses given to women at risk of preterm birth 7 or more days after an initial course. Ten trials were included involving over 4730 women and 5700 infants. Treatment with repeat dose(s) compared with no repeat treatment reduced the risk of respiratory distress syndrome (risk ratio, 0.83; 95% confidence interval, 0.75 0.91) and serious neonatal morbidity (risk ratio, 0.84; 95% confidence interval, 0.75-0.94). At 2- to 3-year follow-up (4 trials, 4170 children), there was no evidence of either significant benefit or harm. Repeat doses of glucocorticoids should be considered in women at risk of preterm birth 7 or more days after an initial course, in view of the neonatal benefits. PMID- 21982022 TI - Seasonal variation in fetal growth: accounting for sociodemographic, biological, and environmental exposures. AB - OBJECTIVE: We sought to investigate seasonal variation in fetal growth, accounting for important sociodemographic, biological, and environmental exposures. STUDY DESIGN: Records of births 1998 through 2006 in Perth, Western Australia were obtained (N = 147,357). We investigated small for gestational age and sex and the proportion of optimal birthweight (POBW) in relation to seasonal exposures (season, temperature, sunlight) by trimester of pregnancy. Adjustment was made for a wide range of risk factors. RESULTS: The POBW for neonates with third trimesters predominantly in summer was 0.18% (0.00-0.36%) lower than for those in winter. POBW decreased by 0.14% (0.01-0.27%) per interquartile range increase in third-trimester temperature (9.15 degrees C). An interquartile range increase in temperature over pregnancy (0.73 degrees C) was associated with an odds ratio of 1.02 (95% confidence interval, 1.00-1.05) for small for gestational age and sex. CONCLUSION: Reduced fetal growth was associated with elevated ambient temperatures throughout and late in pregnancy, independently of air pollution and other risk factors. PMID- 21982023 TI - Mortality and morbidity in preterm small-for-gestational-age infants: a population-based study. AB - OBJECTIVE: We sought to evaluate the impact of severity of growth restriction on mortality and major neonatal morbidity among very-low-birthweight small-for gestational-age infants. STUDY DESIGN: This was a population-based observational study using data collected by the Israel National Very-Low-Birth-Weight Infant Database 1995 through 2007 including infants 24-31 weeks' gestation, with birthweight (BW) <= 50th percentile without major malformations. Four BW percentile groups were considered: < 3rd, 3rd-< 10th, 10th-< 25th, and a reference group 25th-50th percentile. Univariate and multivariable logistic regression analyses were performed. RESULTS: Infants of BW 3rd-< 10th percentile were at increased risk for grades 3-4 retinopathy of prematurity (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.54-2.78), bronchopulmonary dysplasia (OR, 2.52; 95% CI, 2.03-3.12), necrotizing enterocolitis (OR, 1.32; 95% CI, 1.04 1.68), and mortality (OR, 2.37; 95% CI, 1.94-2.90). The risk was further increased among infants of BW < 3rd percentile. CONCLUSION: Growth restriction severity may serve as a clinical marker of degree of risk for neonatal mortality and various morbidities. PMID- 21982024 TI - Folic acid supplementation in early pregnancy and asthma in children aged 6 years. AB - OBJECTIVE: The objective of the study was to assess whether folic acid intake during the first trimester of pregnancy is related to asthma in the offspring by the age of 6 years. STUDY DESIGN: This was a prospective cohort study of 1499 women who were followed up from the first trimester of pregnancy. Their children were followed up until they were 6 years old. RESULTS: Fifty-one percent of the women used folic acid in the month before conception and 88% in the third month of pregnancy. The adjusted odds ratio for asthma per 100 MUm increase in the average daily intake of folic acid was 0.98 (95% confidence interval, 0.93-1.04). For categories of daily folate intake, there was no evidence of associations with childhood asthma or evidence of any dose response relation for any time period (all P(trend) > .05). CONCLUSION: Our results do not support any association of folic acid supplementation in pregnancy and asthma risk in offspring by age 6 years. PMID- 21982025 TI - Peripartum hysterectomy in the United States: nationwide 14 year experience. AB - OBJECTIVE: The objective of the study was to examine the trends in the rate of peripartum hysterectomy and the contribution of changes in maternal characteristics to these trends. STUDY DESIGN: This was a cross-sectional study of peripartum hysterectomy identified from hospitalizations for delivery recorded in the 1994-2007 Nationwide Inpatient Sample. RESULTS: The overall rate of peripartum hysterectomy increased by 15% during the study period. The rate of hysterectomy for abnormal placentation increased by 1.2-fold; adjustment for previous cesarean delivery explained nearly all of this increase. The rate of hysterectomy for uterine atony following repeat cesarean delivery increased nearly 4-fold, following primary cesarean delivery approximately 2.5-fold, and following vaginal delivery about 1.5-fold. This fast growing trend in peripartum hysterectomy secondary to uterine atony was also largely explained by increasing rates of primary and repeat cesareans. CONCLUSION: Rates of peripartum hysterectomy increased substantially in the United States from 1994 to 2007; much of this increase was due to rising rates of cesarean delivery. PMID- 21982026 TI - Antiepileptic drug combinations--have newer agents altered clinical outcomes? AB - In 2000, 332 (20.5%) of 1617 patients registered with the Western Infirmary Epilepsy Unit required antiepileptic drug (AED) polytherapy to remain seizure free for at least 1 year. The analysis was repeated 10 years later. Of 2379 seizure-free patients, 20.4% (n=486 - 254 women, 232 men, aged 18-95 years [median age 49 years]) were receiving combination therapy. Two AEDs were taken by 395 (81.3%) patients in 2010, and by 287 (86.4%) in 2000. Sodium valproate with lamotrigine was the commonest of 64 successful pairings. As a combination, mean daily doses of both AEDs were lower (n=96; sodium valproate 1200 mg, lamotrigine 155 mg) than when sodium valproate was taken with carbamazepine or levetiracetam (n=42; 1621 mg; p<0.001), and lamotrigine was combined with topiramate or levetiracetam (n=33; 430 mg; p<0.001), suggesting possible synergism. In 2010, a higher percentage of patients (n=85) remained seizure-free on 3 AEDs (17.5% in 2010, 12.7% in 2000) in 57 separate regimens. Only 0.9% (n=3) of patients in 2000, and 1.2% (n=6) in 2010 responded to 4 AEDs. Levetiracetam (n=109; 10.2%) and topiramate (n=81; 7.6%) were the newer agents most commonly represented in successful combinations. These data tend to imply that drug substitution rather than addition has largely led to these marginally improved results. In the last decade, when used as adjunctive therapies, newer agents appear not to have impacted substantially on the likelihood of producing seizure freedom. An alternative approach to AED development may be required to change this disappointing scenario. PMID- 21982027 TI - A spatial multicriteria decision making tool to define the best agricultural areas for sewage sludge amendment. AB - Sewage sludge amendment on agricultural soils has recently become a practice of heightened interest, as a consequence of sewage sludge production increase. This practice has benefits to soil and crops, however it may also lead to environmental contamination, depending on the characteristics of the fields. In order to define the suitability of the different agricultural fields to receive sewage sludge, a spatial tool is proposed. This tool, elaborated in GIS platform, aggregates different criteria regarding human exposure and environmental contamination. The spatial tool was applied to a case study in the region of Catalonia (NE of Spain). Within the case study, each step of the tool development is detailed. The results show that the studied region has different suitability degrees, being the appropriate areas sufficient for receiving the total amount of sewage sludge produced. The sensitivity analysis showed that "groundwater contamination", "distance to urban areas", "metals concentration in soil" and "crop type" are the most important criteria of the evaluation. The developed tool successfully tackled the problem, providing a comprehensive procedure to evaluate agricultural land suitability to receive sewage sludge as an organic fertilizer. Also, the tool implementation gives insights to decision makers, guiding them to more confident decisions, based on an extensive group of criteria. PMID- 21982028 TI - Arsenic in North Carolina: public health implications. AB - Arsenic is a known human carcinogen and relevant environmental contaminant in drinking water systems. We set out to comprehensively examine statewide arsenic trends and identify areas of public health concern. Specifically, arsenic trends in North Carolina private wells were evaluated over an eleven-year period using the North Carolina Department of Health and Human Services database for private domestic well waters. We geocoded over 63,000 domestic well measurements by applying a novel geocoding algorithm and error validation scheme. Arsenic measurements and geographical coordinates for database entries were mapped using Geographic Information System techniques. Furthermore, we employed a Bayesian Maximum Entropy (BME) geostatistical framework, which accounts for geocoding error to better estimate arsenic values across the state and identify trends for unmonitored locations. Of the approximately 63,000 monitored wells, 7712 showed detectable arsenic concentrations that ranged between 1 and 806MUg/L. Additionally, 1436 well samples exceeded the EPA drinking water standard. We reveal counties of concern and demonstrate a historical pattern of elevated arsenic in some counties, particularly those located along the Carolina terrane (Carolina slate belt). We analyzed these data in the context of populations using private well water and identify counties for targeted monitoring, such as Stanly and Union Counties. By spatiotemporally mapping these data, our BME estimate revealed arsenic trends at unmonitored locations within counties and better predicted well concentrations when compared to the classical kriging method. This study reveals relevant information on the location of arsenic-contaminated private domestic wells in North Carolina and indicates potential areas at increased risk for adverse health outcomes. PMID- 21982029 TI - A multidisciplinary weight of evidence approach for classifying polluted sediments: Integrating sediment chemistry, bioavailability, biomarkers responses and bioassays. AB - Evaluation of chemical bioavailability and onset of biological alterations is fundamental to assess the hazard of environmental pollutants, particularly when associated to sediments which need to be removed. In the present work, five sediment samples were collected from the Venice Lagoon and data from sediment chemistry were integrated with those of bioaccumulation of chemicals in European eel (Anguilla anguilla) exposed under laboratory conditions, responses of a wide battery of biomarkers, and standardized ecotoxicological bioassays. The overall results were elaborated within a recently developed, software-assisted weight of evidence (WOE) model which provides synthetic indices for each of considered line of evidence (LOE), before a general evaluation of sediment hazard. Levels of chemicals in sediments were not particularly elevated when compared to sediment quality guidelines of Venice Protocol. On the other hand, bioavailability was evident in some samples for Cd, Cu, Zn and, especially, polycyclic aromatic hydrocarbons. The ecotoxicological approach provided further evidence on the biological and potentially harmful effects due to released contaminants, and oxidative-mediated responses appeared of primary importance in modulating sublethal responses and the onset of cellular alterations. Biomarkers variations were sensitive, and more evident variations included significant changes of cytochrome P450 biotransformation pathway, antioxidant responses, onset of oxidative damages, lysosomal membrane stability and genotoxic effects. The results obtained from the battery of bioassays indicated that responses measured at organism level were in general accordance but less marked compared to the onset of sublethal changes measured through biomarkers. Overall this study revealed differences when comparing evaluations obtained from different LOEs, confirming the importance of considering synergistic effects between chemicals in complex mixtures. Compared to a qualitative pass-fail approach toward normative values, the proposed WOE model allowed a quantitative characterization of sediment hazard and a better discrimination of on the basis of various types of chemical and biological data. PMID- 21982030 TI - Cohort study on the effects of everyday life radio frequency electromagnetic field exposure on non-specific symptoms and tinnitus. AB - BACKGROUND: There is public concern regarding potential health effects of radio frequency electromagnetic fields (RF-EMF) exposure, as produced by mobile phones or broadcast transmitters. The objective of this study was to investigate the association between RF-EMF exposure and non-specific symptoms and tinnitus in a prospective cohort study. METHODS: In 2008, 1375 randomly selected participants from Basel, Switzerland, were enrolled in a questionnaire survey with follow-up after one year (participation rate 82%). A score for somatic complaints (von Zerssen list) and headache (HIT-6) was assessed. Far-field environmental RF-EMF exposure was predicted using a validated prediction model. Regarding near-field exposure, self-reported mobile and cordless phone use as well as mobile phone operator data were collected. In multivariate regression models, we investigated whether exposure at baseline (cohort analysis) or changes in exposure between baseline and follow-up (change analysis) were related to changes in health scores. RESULTS: For participants in the top decile of environmental far-field RF EMF exposure at baseline, in comparison to participants exposed below the median value, the change in the von Zerssen- and HIT-6-scores between baseline and follow-up was -0.12 (95%-CI: -1.79 to 1.56) and -0.37 (95%-CI: -1.80 to 1.07) units, respectively. Exposure to near-field sources and a change in exposure between baseline and follow-up were not related to non-specific symptoms. Similarly, no association between RF-EMF exposure and tinnitus was observed. CONCLUSIONS: In this first cohort study using objective and well-validated RF-EMF exposure measures, we did not observe an association between RF-EMF exposure and non-specific symptoms or tinnitus. PMID- 21982031 TI - Proximity to wood industries and respiratory symptoms in children: a sensitivity analysis. AB - Increased prevalence of respiratory and irritation symptoms was found in children who live near a large wood industrial park. Proximity to the wood industries was used as indicator of exposure. This study describes a sensitivity analysis for the results of the survey. All the children (3-14 years) living in the area were surveyed through a parental questionnaire (n=3854) and their addresses were geocoded. The distances from each child's home and school to the closest industry were combined, weighted and used as an indicator of exposure. A sensitivity analysis was performed to check 1) the robustness of the results to the choice of weights used for defining the exposure indicator, 2) the effect of outliers on risk estimates and 3) the sensitivity on the functional form used for modeling the dose-response function. The choice of the weights did not influence the association between proximity to the industries and respiratory symptoms. Excluding the subjects who lived far away from the industries showed that in a radius of 5km from the industries the study did not had enough power to estimate a gradient in the dose-response function. Besides, results were sensitive to the choice of the functional form used for modeling the minimum distance. The sensitivity analyses confirmed the overall increasing trend of respiratory symptoms with proximity to the industries and pointed out that all the assumptions made for defining a proxy of exposure need to be carefully checked. PMID- 21982032 TI - Co-leaching of brominated compounds and antimony from bottled water. AB - A fast-growing bottled water market is occasionally challenged by reports calling for contaminant leaching from water-contact materials (plastics). Our focus was on leaching of antimony (Sb) and brominated compounds expressed by total soluble bromine (Br) measurements, including those of polybrominated diphenyl ethers (PBDE). Studies are lacking on concomitant leaching of two or more inorganic plastic constituents from the same bottle. A market-representative basket survey of bottled water was initiated in Boston, USA supermarkets. Bottled water classes sampled were: i) non-carbonated (NCR), ii) carbonated (CR), and iii) non carbonated and enriched (NCRE). Plastic bottle materials sampled were: polyethylene terephthalate (PET), high-density polyethylene (HDPE), polystyrene (PS), and polycarbonate (PC). Storage conditions for the 31 bottled water samples were: 23 degrees C temperature, no-shaking and 12h/12h light/dark for 60days of equilibration. Average Br and Sb concentrations after 60-days of storage followed the order of NCR=0.1). Therefore, the pigs' exposure above the EU limit during the early fattening stage did not necessarily lead to their categorization as non-compliant pork; and the residual TEQ for pork can be predicted from early exposure concentrations based on the models established here. PMID- 21982037 TI - Maternal exposure to high levels of dioxins in relation to birth weight in women affected by Yusho disease. AB - BACKGROUND: Studies on the association of maternal exposure to polychlorinated dibenzo-p-dioxin (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) with decreased birth weight in humans have produced conflicting results. In Japan in 1968, an accidental human exposure to rice oil contaminated with PCDDs, PCDFs, and PCBs, led to the development of Yusho disease. OBJECTIVE: The Yusho cohort was used to evaluate the effect of maternal exposure to PCDDs, PCDFs, and PCBs on birth weight. METHODS: Blood samples, obtained from 101 Yusho women (190 births) who gave birth after exposure, were analyzed for congeners of seven PCDDs, ten PCDFs, and four non ortho PCBs. RESULTS: Total PCDD TEQ (adjusted beta=-161.9g; 95% CI, -265.3 to 58.6), total PCDF TEQ (adjusted beta=-105.9g; 95% CI, -179.5 to -32.2), and total non-ortho PCBs (adjusted beta=-178.4g; 95% CI, -318.3 to -38.5) levels were inversely associated with birth weight. Significant inverse associations with birth weight were also found for total PCDD TEQ, total PCDF TEQ, and total non ortho PCB TEQ levels among male, but not female, infants. Significant inverse associations with birth weight were also found for nine congeners among all infants; the adjusted beta coefficients were largest for 1,2,3,6,7,8-HxCDD and smallest for 2,3,4,7,8-PeCDF. CONCLUSION: In the setting of exposure to high levels of dioxins, maternal blood levels of PCDDs, PCDFs and PCBs are associated with lower birth weight in Yusho patients. The association exhibited gender specific differences, as male infants are more susceptible than females to growth restriction induced by in utero dioxin exposures. PMID- 21982038 TI - What defines extraintestinal pathogenic Escherichia coli? AB - Escherichia coli (E. coli) exhibits considerable physiological and metabolic versatility and includes a variety of non-pathogenic, commensal variants, which belong to the normal gut flora of humans and warm-blooded animals. Additionally, several pathogenic variants have been identified which cause various types of intestinal or extraintestinal infections in humans and animals. In contrast to intestinal pathogenic E. coli (IPEC), which are obligate pathogens, extraintestinal pathogenic E. coli (ExPEC) are facultative pathogens which belong to the normal gut flora of a certain fraction of the healthy population where they live as commensals. Comparative genomics and epidemiological studies have been applied to study genomic diversity, markers, and phenotypic traits that may support discrimination of different E. coli pathotypes. Whereas IPEC are often epidemiologically and phylogenetically distinct from ExPEC and non-pathogenic, commensal strains, many ExPEC and non-pathogenic E. coli share large genomic fractions. Furthermore, extraintestinal infections of elderly or immunocompromised patients can be caused by E. coli variants which differ in their geno- and phenotypes from archetypal ExPEC. Thus, strain typing based on the detection of a limited number of ExPEC virulence/fitness-related genes may be ambiguous. A limited number of ExPEC-dominated clonal complexes can be identified in the E. coli population by multi locus sequence typing. Nevertheless, ExPEC and non-pathogenic E. coli cannot be clearly discriminated by molecular epidemiological approaches. Increased knowledge of the phylogeny, virulence and fitness traits, and host factors contributing to host susceptibility of the different groups of ExPEC variants is required for a better understanding of the biological basis of ExPEC infections. PMID- 21982039 TI - Assessment of autonomic control of the heart during transient myocardial ischemia. AB - INTRODUCTION: In the presence of coronary artery obstruction, complex cardiovascular reflexes may lead to changes in heart rate and even to the precipitation of malignant arrhythmias. The autonomic nervous system (ANS) has traditionally been considered to be "balanced" between continuously interacting sympathetic and parasympathetic outflows. The purpose of this study was to assess ANS control of the heart during prolonged coronary balloon occlusion procedures of one of the major coronary arteries. METHODS: R-R intervals were obtained from continuous electrocardiographic data of 90 patients undergoing selective percutaneous coronary interventions (PCI) with balloon inflation periods ranging from 3 to 10 minutes (4.7 +/- 1.1 minutes). Three 3-minute stages were chosen: (1) preinflation (baseline), (2) from the start of occlusion (PCI), and (3) immediately post deflation. The dynamics of the ANS was evaluated by heart rate variability analysis using standard time and frequency domain indices and the short-term fractal-like index (alpha(1)). RESULTS: During PCI, time and frequency domain measures related to vagal control decreased significantly with respect to baseline (significantly in left anterior descending [LAD] artery occlusions). During the postdeflation stage, heart rate variability and high-frequency power increased (P < .01) in the group with right coronary artery occlusions, whereas a marked sympathetic increase, as assessed by an increase (P < .01) of normalized low-frequency power and the low/high-frequency ratio was observed in the LAD group after balloon deflation. Fractal index alpha(1) decreased during the PCI period but increased significantly after balloon deflation. CONCLUSIONS: Significant changes in autonomic control of heart rate that were a function of the affected artery occurred during and after coronary artery occlusions. Occlusion of the LAD resulted in a significant reduction of vagal activity and a decrease of the short-term fractal index during PCI and a marked sympathetic response after postdeflation. However, a marked increment of vagal activity between the occlusion stage and postdeflation period was found in the right coronary artery group. These results may relate the site of the occlusion and lack of blood supply to different parts of the left ventricle. PMID- 21982040 TI - Specificity of the wide QRS complex tachycardia algorithms in recipients of cardiac resynchronization therapy. AB - BACKGROUND: We assessed the specificity of wide QRS complex tachycardia (WCT) differentiating algorithms in patients with preexistent left bundle branch block (LBBB) and heart failure. METHODS: Three hundred fourteen patients with resynchronization devices were retrospectively screened. electrocardiograms with supraventricular LBBB rhythm were used as a surrogate for supraventricular tachycardia QRS morphology. The Pava lead II criterion, ventricular activation velocity ratio (Vi/Vt) ratio in V(2), Vereckei aVR, Brugada, Griffith, and Bayesian algorithms were investigated. RESULTS: The WCT algorithms had a lower specificity (33%-69%) in patients with LBBB than in general WCT populations. The Pava lead II criterion and Brugada algorithm had higher specificity than other algorithms (P < .05). Several of the single criteria (absence of an RS complex in V(1) through V(6), initial R wave in aVR, Vi/Vt < 1 in V(2)) had specificities of 92% to 99%. CONCLUSIONS: In patients with heart failure and LBBB, an electrocardiographic diagnosis of ventricular tachycardia should be based on selected, specific criteria rather than on WCT algorithms. PMID- 21982041 TI - [The paradigm of osteoporotic fractures of the male and female]. PMID- 21982042 TI - [Pyogenic and tuberculous abscesses of the psoas muscle]. AB - OBJECTIVES: To describe the clinical characteristics of patients with abscess on the psoas muscle (PA) and to identify the possible differences existing between pyogenic and tuberculous etiologies. PATIENTS AND METHODS: A retrospective review of patients diagnosed of PA in one hospital was conducted (1983-2009). Two groups were established, that is pyogenic and tuberculous, and the clinical findings, analyses and evolution were compared. RESULTS: Thirty PA were included, 83% pyogenic and 17% tuberculous, average age 53 years. On 9 occasions, 30% were primary and on 21 occasions, 70% secondary (to skeletal pathology in 8, to urological in 8 and to gastrointestinal in 8). No clinical differences were observed between both groups. Pyogenic and tuberculous etiologies were differentiated analytically through leukocyte values (13,871 vs. 8,560/mm(3), p=0.018), hemoglobin (11 vs. 14 g/dL, p=0.008) and erythrocyte sedimentation rate (ESR) (108 vs. 17 mm/h, p<0.0001). Abscesses were diagnosed by computed tomography (CT) in 29 patients (97%) and by magnetic resonance in 1 (3%), both with a diagnostic sensitivity of 100%, as opposed to 50% for ultrasound scanning. Left laterality was less frequent in pyogenic abscesses (44% vs. 100%, p=0.031). The blood cultures were positive in 22% and abscess pus culture in 82%. Gram negative bacilli, Streptococcus spp. and S. aureus were the most frequent isolations. A total of 67% were drained: transcutaneously 50%, surgically 13% and both techniques 3%. Two patients died (7%), both with pyogenic abscess. CONCLUSIONS: Secondary pyogenic abscesses constitute the most frequent PA group. CT is the diagnostic procedure of choice. Leukocytosis, anemia, raised ESR and right laterality suggest pyogenic etiology. Transcutaneous drainage is substituting surgical drainage and also makes it possible to obtain diagnostic samples. PMID- 21982044 TI - Immunoexpression of B7-H3 in endometrial cancer: relation to tumor T-cell infiltration and prognosis. AB - OBJECTIVE: B7-H3, a member of the B7 family of immune regulatory ligands regulates T cell-mediated peripheral immune response. The purpose of this study was to correlate the expression of B7-H3 and number of lymphocytes in patients with endometrial cancer. MATERIAL AND METHODS: A total of 107 patients with primary endometrial carcinoma (type I/endometrioid, n=81; type II, n=18) and endometrial hyperplasia (n=8) were investigated. Expression of B7-H3 in endometrial hyperplasia, endometrial carcinoma, and the endothelium of tumor associated vasculature was assessed using immunohistochemistry from paraffin embedded tissue blocks. Detection of CD8-positive tumor-infiltrating lymphocytes (TIL) and CD8-positive tumor-associated lymphocytes (TAL) was correlated with the expression of B7-H3. RESULTS: Patients with high grade tumors and patients with type II carcinomas expressed significantly more B7-H3 than low grade and endometrioid tumors (p=<0.0001 and p=0.0001, respectively). The expression of B7 H3 in the endothelium of identified vasculature in the tumor specimens showed similar results with strong relation to high grade tumors (p=0.001) and type II carcinomas (p=0.004). We found a significant correlation between B7-H3 expression on cancer cells and tumor T-cell infiltration (TIL) (p=0.017). In a univariate survival analysis, overexpression of B7-H3 in tumor cells was associated with shortened overall survival (p=0.005). CONCLUSIONS: B7-H3 is overexpressed on cancer cells and in the endothelium of tumor-associated vasculature in high grade tumors (G3) and type II carcinomas. B7-H3 expression on cancer cells is correlated with the number of T cells infiltrating the tumor. Endometrium tumor development and progression may be associated with downregulation of T-cell mediated antitumor immunity through B7-H3. PMID- 21982045 TI - "Kegel ball" induced vaginal cuff dehiscence following radical abdominal hysterectomy: laparoscopically-assisted transvaginal retrieval. PMID- 21982043 TI - [Comorbidity, discapacity and mortality in patients with multiple conditions and chronic obstructive pulmonary disease]. AB - AIMS: To determine the association between different comorbidities and other clinical conditions with mortality in patients with multiple diseases (PMD) suffering from chronic obstructive pulmonary disease (COPD). SUBJECTS AND METHODS: Patients with COPD and PMD criteria were included in an observational, prospective and multicentrer study. Data on age, gender, Charlson index, Barthel index, Lawton-Brody index, Pfeiffer test, sociofamilial Gijon scale, education level, hospitalizations during the previous 3 and 12 months and survival at one year were collected. The relationship between the variables and mortality were established by means of a univariate analysis and logistic regression model. RESULTS: A total of 688 PMD with COPD and mean age of 77.9 years were included. The mean score one the Charlson index was 3.99 (2.07). The most frequent comorbidities were heart failure (59%), diabetes (48%), myocardial infarction (29%), moderate kidney failure (22%), cerebrovascular disease (19%), hypertension (71%), anemia (62%), atrial fibrillation (34%), dyslipidemia (28%) and obesity (21%). A total of 26% of patients were dependent for activities of daily living, 47% needed a caregiver and 54% were at risk of having social problems. At one year, 258 patients (37%) had died. The Charlson index, dependency for activities of daily living and anemia were associated with mortality and hypertension and capacity for reading and writing were associated with survival. CONCLUSIONS: Comorbidity and discapacity are two prognostic factors in COPD patients. PMID- 21982046 TI - Patterns of first recurrence following adjuvant intraperitoneal chemotherapy for stage IIIC ovarian cancer. AB - OBJECTIVE: Adjuvant intraperitoneal (IP) platinum-based chemotherapy has been shown to improve outcome for patients with advanced ovarian cancer. We hypothesize that patients who have received adjuvant IP chemotherapy more commonly recur first at extraperitoneal sites than patients who have received adjuvant intravenous (IV) chemotherapy. METHODS: Patients with newly diagnosed stage IIIC optimally debulked serous ovarian cancer were identified from institutional databases. Patterns of recurrence were compared between patients who received IV and IP chemotherapy using standard two-sided statistical tests. RESULTS: Of the 104 patients who met inclusion criteria, 60 received IV chemotherapy and 44 received IP chemotherapy. Patients in the IV group had a first recurrence more commonly in the lower abdomen or pelvis than the IP group. Patients in the IP group more commonly recurred in the upper abdomen and extra abdominal lymph nodes. More patients in the IP group than the IV group recurred at extra-abdominal sites (45.5% versus 23.3%, P=0.018). CONCLUSIONS: Patients receiving adjuvant IP chemotherapy are less likely to first recur in the lower abdomen or pelvis and more likely to recur outside of the abdominal cavity. The data suggest that IP chemotherapy is highly effective in the anatomic areas of peritoneal distribution. PMID- 21982047 TI - Lymph node metastasis in stages I and II ovarian cancer: a review. AB - OBJECTIVES: The purpose of this review is to determine the incidence of lymph node metastases in clinical stages I and II ovarian cancer. METHODS: Relevant articles were identified from MEDLINE and EMBASE, supplemented with citations from reference lists from the primary studies. Eligibility was evaluated by two authors. Included studies were prospective or retrospective cohort studies, which analyzed patients with clinical early stage EOC who underwent a complete pelvic and para-aortic lymphadenectomy as a part of a staging laparotomy. RESULTS: Fourteen studies were included in the analysis. The mean incidence of lymph node metastases in clinical stages I-II EOC was 14.2% (range 6.1-29.6%), of which 7.1% only in the para-aortic region, 2.9% only in the pelvic region, and 4.3% both in the para-aortic and pelvic region. Grade 1 tumors had a mean incidence of lymph node metastases of 4.0%, grade 2 tumors 16.5.8% and grade 3 tumors 20.0%. According to histological subtype, the highest incidence of lymph node metastases was found in the serous subtype (23.3%), the lowest in the mucinous subtype (2.6%). In unilateral tumors, pelvic lymph node metastases were found in 9.7% on both sides, 8.3% only at the ipsilateral side, and in 3.5% only at the contralateral side. CONCLUSIONS: The incidence of lymph node metastases in clinical early stage EOC is considerable. Based on the scarce literature data, omitting a systematic lymphadenectomy can only be considered in grade I mucinous tumors. PMID- 21982048 TI - Heterogeneity in the selection of quinolone target gene mutations upon exposure to ciprofloxacin in Yersinia enterocolitica. PMID- 21982049 TI - Effect of telavancin on human intestinal microflora. AB - Telavancin is a new lipoglycopeptide antibiotic for the treatment of Gram positive infections. It has a dual mechanism of action by inhibiting bacterial cell wall synthesis and disrupting the bacterial plasma membrane. The purpose of the present study was to investigate the effect of administration of telavancin on the human intestinal microflora. Thirteen healthy subjects (six males and seven females; age range 18-40 years) received 10mg/kg body weight telavancin by intravenous infusion over a 60-min period once every 24h for 7 days. Plasma and urine were collected on Days 5, 6 and 7 for pharmacokinetic analysis of telavancin. Faecal samples were collected on Days -1 (pre-dose), 2, 5, 7, 9, 14 and 21. Faecal specimens were cultured on non-selective and selective media. Different colony types were counted, isolated in pure culture and identified to genus level. No measurable concentrations of telavancin were found in faeces. No significant effects on the number of Enterobacteriaceae, enterococci, Candida albicans, bifidobacteria, lactobacilli, clostridia and Bacteroides spp. were observed during the study period. No Clostridium difficile strains or toxins were found. No new colonising aerobic and anaerobic Gram-positive bacteria with telavancin minimum inhibitory concentrations of >= 2 mg/L were found. Based on the microbiological data, telavancin has no significant ecological impact on the human intestinal microflora. PMID- 21982050 TI - A ward-based writing coach program to improve the quality of nursing documentation. AB - A ward-based writing coach program was piloted at a metropolitan hospital in Australia to produce a quality improvement in nursing documentation. This paper describes the education program, which consisted of two writing workshops, each of one-hour duration followed by one-to-one coaching of nurses. This program could be carried out in any clinical area as a part of the regular education program. Nurses are encouraged to view their documentation practices in a critical light to ensure that the documentation is meaningful to readers within or outside the profession. The importance of nursing documentation as a communication tool for all health care professionals is emphasised. Barriers to meaning, such as fragmentary language or the use of unofficial abbreviations, are discussed. Nurses are also encouraged to document the patient's condition, care and response to care using defined principles for nursing documentation. This program would be transferrable to any clinical setting looking for a ward-based education program for nursing documentation. PMID- 21982051 TI - Cholestatic hepatitis in a patient with typhoid fever - a case report. AB - Typhoid fever is a very common infectious disease, particularly in developing countries such as Sri Lanka. Although multiple organs are known to be affected by the disease, hepatic involvement could be considered the most important as studies have showed that it is associated with a higher relapse rate. We report a young patient who presented with fever and jaundice and found to have cholestatic hepatitis secondary to typhoid fever. PMID- 21982052 TI - The effect of an educational intervention on coronary artery bypass graft surgery patients' participation rate in cardiac rehabilitation programs: a controlled health care trial. AB - BACKGROUND: Cardiac rehabilitation has a beneficial effect on the prognosis and quality of life of cardiac patients, and has been found to be cost-effective. This report describes a comprehensive and low cost educational intervention designed to increase the attendance at cardiac rehabilitation programs of patients who have undergone coronary artery bypass graft surgery. METHODS/DESIGN: A controlled prospective intervention trial. The control arm comprised 520 patients who underwent coronary artery bypass graft surgery between January 2004 and May 2005 in five medical centers across Israel. This group received no additional treatment beyond usual care. The intervention arm comprised 504 patients recruited from the same cardiothoracic departments between June 2005 and November 2006. This group received oral and written explanations about the advantages of participating in cardiac rehabilitation programs and a telephone call two weeks after hospital discharge intended to further encourage their enrollment. The medical staff attended a one-hour seminar on cardiac rehabilitation. In addition, it was recommended that referral to cardiac rehabilitation be added to the letter of discharge from the hospital. Both study groups were interviewed before surgery and one-year post surgery. A one-year post operative interview assessed factors affecting patient attendance at cardiac rehabilitation programs, as well as the structure and content of the cardiac rehabilitation programs attended. Anthropometric parameters were measured at pre- and post-operative interviews;- and medical information was obtained from patient medical records. The effect of cardiac rehabilitation on one- and three-year mortality was assessed. DISCUSSION: We report a low cost yet comprehensive intervention designed to increase cardiac rehabilitation participation by raising both patient and medical staff awareness to the potential benefits of cardiac rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00356863. PMID- 21982053 TI - Tannin extracts from immature fruits of Terminalia chebula Fructus Retz. promote cutaneous wound healing in rats. AB - BACKGROUND: Tannins extracted from immature fruits of Terminalia chebula Fructus Retz. are considered as effective components promoting the process of wound healing. The objective of this study is to explore the optimal extraction and purification technology (OEPT) of tannins, while studying the use of this drug in the treatment of a cutaneous wound of rat as well as its antibacterial effects. METHODS: The content of tannin extracts was measured by the casein method, and antibacterial ability was studied by the micro-dilution method in vitro. In wound healing experiment, animals in group I, II and III were treated with vaseline ointment, tannin extracts (tannin content: 81%) and erythromycin ointment, respectively (5 mg of ointment were applied on each wound). To evaluate the process of wound healing, selected pharmacological and biochemical parameters were applied. RESULTS: After optimal extraction and purification, content of tannin extracts was increased to 81%. Tannin extracts showed the inhibition of Staphylococcus aureus and Klebsiella Pneumonia in vitro. After excision of wounds, on days 7 and 10, the percent of wound contraction of group II was higher than that of group I. After being hurt with wounds, on days 3, 7, and 10, the wound healing quality of group II was found to be better than that of group I in terms of granulation formation and collagen organization. After wound creation, on day 3, the vascular endothelial growth factor expression of group II was higher than that of group I. CONCLUSION: The results suggest that tannin extracts from dried immature fruits of Terminalia chebula Fructus Retz. can promote cutaneous wound healing in rats, probably resulting from a powerful anti bacterial and angiogenic activity of the extracts. PMID- 21982054 TI - Mapping biomass with remote sensing: a comparison of methods for the case study of Uganda. AB - BACKGROUND: Assessing biomass is gaining increasing interest mainly for bioenergy, climate change research and mitigation activities, such as reducing emissions from deforestation and forest degradation and the role of conservation, sustainable management of forests and enhancement of forest carbon stocks in developing countries (REDD+). In response to these needs, a number of biomass/carbon maps have been recently produced using different approaches but the lack of comparable reference data limits their proper validation. The objectives of this study are to compare the available maps for Uganda and to understand the sources of variability in the estimation. Uganda was chosen as a case-study because it presents a reliable national biomass reference dataset. RESULTS: The comparison of the biomass/carbon maps show strong disagreement between the products, with estimates of total aboveground biomass of Uganda ranging from 343 to 2201 Tg and different spatial distribution patterns. Compared to the reference map based on country-specific field data and a national Land Cover (LC) dataset (estimating 468 Tg), maps based on biome-average biomass values, such as the Intergovernmental Panel on Climate Change (IPCC) default values, and global LC datasets tend to strongly overestimate biomass availability of Uganda (ranging from 578 to 2201 Tg), while maps based on satellite data and regression models provide conservative estimates (ranging from 343 to 443 Tg). The comparison of the maps predictions with field data, upscaled to map resolution using LC data, is in accordance with the above findings. This study also demonstrates that the biomass estimates are primarily driven by the biomass reference data while the type of spatial maps used for their stratification has a smaller, but not negligible, impact. The differences in format, resolution and biomass definition used by the maps, as well as the fact that some datasets are not independent from the reference data to which they are compared, are considered in the interpretation of the results. CONCLUSIONS: The strong disagreement between existing products and the large impact of biomass reference data on the estimates indicate that the first, critical step to improve the accuracy of the biomass maps consists of the collection of accurate biomass field data for all relevant vegetation types. However, detailed and accurate spatial datasets are crucial to obtain accurate estimates at specific locations. PMID- 21982055 TI - In vivo vitiligo induction and therapy model: double-blind, randomized clinical trial. AB - In this study, we developed an in vivo vitiligo induction model to explore the underlying mechanisms leading to Koebner's phenomenon and to evaluate the efficacy of therapeutic strategies. The model consisted of 12 pigmented test regions on the back of generalized vitiligo patients that were exposed to three Koebner induction methods: cryotherapy, 755 nm laser therapy, and epidermal abrasion. In addition, four cream treatments (pimecrolimus, tacrolimus, steroid and placebo) were randomly applied. Koebnerization was efficiently induced by all three induction methods. In general, cryotherapy was the best method of Koebner induction, followed by 755 nm laser therapy and epidermal abrasion. Reproducible results were obtained, which showed enhanced depigmented surface areas and higher amounts of T lymphocytes in placebo-treated test zones compared to active treated areas. Tacrolimus and local steroids were better inhibitors of Koebner's process (P < 0.05) compared to pimecrolimus. Our in vivo vitiligo induction model is very informative to investigate vitiligo induction and to determine the efficacy of topical treatments in vitiligo. This proof of concept confirms the efficient comparison of head-to-head therapeutic strategies intra-individually in a standardized, specific and better timed way. PMID- 21982056 TI - Teaching empathy to undergraduate medical students using a temporary tattoo simulating psoriasis. AB - BACKGROUND: Psoriasis has a profound negative effect on quality of life that is often underappreciated by health care professionals and the public. OBJECTIVE: We sought to assess the perception of the burden of psoriasis relative to other medical conditions in first-year medical students, and to determine if wearing a temporary tattoo simulating psoriasis during a teaching exercise would change their perceptions. METHODS: Participants completed a questionnaire assessing their perception of the impact of psoriasis and other common medical conditions (visual analog scale). Participants then wore a temporary tattoo of a psoriatic lesion for 24 hours and completed the same questionnaire after this exercise. RESULTS: Of 91 students approached, 61 completed the study. At baseline, psoriasis (mean = 23.6) and eczema (mean = 23.3) were perceived as having the lowest physical burden of diseases queried (P < .0001), whereas the mental impact of psoriasis was scored comparably with arthritis, heart disease, and diabetes (mean = 45.1-56.7), but lower than cancer (mean = 82.2) and depression (mean = 93.8). After the exercise, the perception of the impact of eczema (physical: mean = 37.3, P < .0001; mental: mean = 66.6, P = .0005) and psoriasis (physical: mean = 37.8, P = .0014; mental: mean = 68.6, P = .0293) was significantly increased. LIMITATIONS: The exercise did not simulate the chronic nature of psoriasis or the scaling and pruritic characteristics of psoriatic lesions. The survey instrument used to assess empathy has not been previously validated and statistical analysis was limited by small sample size and the absence of a control group. CONCLUSIONS: Temporary tattoos are a novel and effective method of teaching medical students about the psychological burden of psoriasis. PMID- 21982057 TI - Fibroblastic rheumatism: a report of 4 cases with potential therapeutic implications. AB - BACKGROUND: Fibroblastic rheumatism is a rare dermatoarthropathy characterized by the sudden onset of cutaneous nodules, flexion contractures, and polyarthritis. Histopathology in the correct clinical context confirms the diagnosis. Treatment is based on observational data from single case reports. OBJECTIVE: We describe 4 cases, review histologic findings, and discuss therapeutic responses. METHODS: Cases coded as fibroblastic rheumatism were retrieved from institutional and consultation files. Medical charts and biopsy specimens were reviewed. Elastic stains and immunostains for smooth muscle actin, S100, CD34, desmin, and epithelial membrane antigen were performed on selected cases. RESULTS: Four cases were identified. Patients displayed cutaneous nodules and arthralgias. Flexion contractures/decreased motion were present in two patients; one patient had associated Raynaud phenomenon and erosive joint disease. Biopsy specimens demonstrated a fibroblastic proliferation associated with a collagenous stroma. Growth patterns varied from cellular fascicles to paucicellular randomly arranged spindle cells. Elastic fibers were absent in all cases tested (3/3). Immunohistochemical stains demonstrated immunoreactivity for smooth muscle actin in one of 3 cases in a myofibroblastic pattern. Other stains were negative. One patient had complete resolution of disease with methotrexate. One patient partially responded to interferon-alfa and ribavirin and was subsequently treated with methotrexate with additional improvement. One patient had limited response to all therapies attempted. One patient was lost to follow-up. LIMITATIONS: Small sample size (n = 4) is a limitation. CONCLUSION: Our data expand the clinical, histologic, and therapeutic response data on fibroblastic rheumatism. Correlation with clinical history is critical to avoid misdiagnosis as other fibrosing lesions. Methotrexate and interferon-alfa are potential therapies. PMID- 21982058 TI - Association between peripheral vascular endothelial dysfunction and livedoid vasculopathy. AB - BACKGROUND: Livedoid vasculopathy (LV) is a disease characterized by multiple painful and recurrent ulcerations on the feet, accompanied by atrophic scars. Many researchers suggest that a hypercoagulable status is the pathogenetic factor for LV. However, the cause of LV remains elusive. OBJECTIVE: We sought to determine if endothelial dysfunction is present in patients with LV. METHODS: This prospective study included 16 patients with LV and active ulcers and 16 matched control subjects. We reviewed detailed clinical parameters, including antinuclear antibody, high-sensitivity C-reactive protein, protein C, protein S, homocysteine, anti-SSA, anti-SSB, anticardiolipin antibody, and serum lipid profiles. Flow-mediated vasodilation of the brachial artery was used as an indicator of vascular endothelial function using high-resolution 2-dimensional ultrasonic imaging. RESULTS: Blood pressure, blood biochemistry, high-sensitivity C-reactive protein, and homocysteine were not significantly different in patients with LV and control subjects. Nitroglycerin-mediated vasodilation was not significantly different in patients with LV and control subjects. However, flow mediated vasodilation was much less in patients with LV than in the control group (3.58 +/- 2.32% vs 7.51 +/- 2.40%, P < .001). LIMITATIONS: The study was performed at a single site with a limited sample size. CONCLUSION: Peripheral vascular endothelial dysfunction was demonstrated in patients with LV by reduction of brachial flow-mediated vasodilation. PMID- 21982059 TI - Hyperpigmented mycosis fungoides: an unusual variant of cutaneous T-cell lymphoma with a frequent CD8+ phenotype. AB - BACKGROUND: Hyperpigmented skin lesions rarely appear as a specific manifestation of mycosis fungoides (MF). OBJECTIVE: To study the clinical, histopathological, and immunohistochemical features of hyperpigmented MF. METHODS: Patients with hyperpigmented MF were identified by a file search of all patients with MF who had attended a cutaneous lymphoma outpatient clinic in the last 15 years, and the relevant data were collected. RESULTS: Eight patients had early-stage MF manifested by hyperpigmented patches and/or flat plaques. All but one had a dark complexion. Mean age at diagnosis was 43 years (range, 19-69), and mean interval from disease onset to diagnosis was 6.25 years (range, 1-14). In 5 patients, the hyperpigmented lesions were the sole manifestation of the disease; in the remainder, they appeared in conjunction with other unusual lesions of MF. Histologically, all our patients had interface changes with melanophages in addition to the classical findings of early MF. Only one patient had a CD4(+) epidermotropic T-cell phenotype; 5 patients had a CD8(+) phenotype, and 2 had a CD4(-)CD8(-) phenotype. Patients received skin-targeted therapies, and all had indolent course without evidence of disease progression after a mean follow-up of 3.8 years. LIMITATIONS: This was a case series descriptive study. CONCLUSION: Hyperpigmented MF is an atypical clinical variant of cutaneous T-cell lymphoma, with a predilection for patients with a dark complexion. It is characterized by a predominantly CD8(+) phenotype. Hyperpigmented lesions may be the sole manifestation or it may coexist with other unusual MF variants typified mostly by pigmentary changes. PMID- 21982060 TI - The local treatment and available dressings designed for chronic wounds. AB - The great diversity of wounds and the broad range of available dressings complicate the selection of proper chronic wound treatment. Choosing the right treatment is the essential step in the healing process. In this review, we focus on chronic nonhealing ulcers, which are a critical problem in clinical practice, and current knowledge about persistent wound care. Here, we present the objectives of local treatment with description of several types of dressings and their ingredients, features, indications, and contraindications. These include hydrocolloid, alginate, hydrogel, and dextranomer dressings; polyurethane foam and membrane dressings; semipermeable polyurethane membrane dressings; and TenderWet (Hartmann, Rock Hill, SC) and flax dressings. There is also a brief section on the use of other alternative wound-healing accelerators, such as platelet-rich plasma and light-emitting diode therapy. PMID- 21982061 TI - Cutaneous Richter syndrome: report of 3 cases from one institution. AB - BACKGROUND: Richter syndrome (RS) is large-cell transformation of chronic lymphocytic leukemia (CLL). It commonly involves lymph nodes and bone marrow, but may rarely manifest in skin. Certain triggering factors, such as Epstein-Barr virus infection and p53 overexpression, have been implicated in the pathogenesis of RS. Here, we present 3 cases of cutaneous RS from our institution with a follow-up period of up to 8 years. OBJECTIVE: We present a series of cutaneous RS from a single institution with the longest follow-up period (up to 8 years) to date. METHODS: Clinical characteristics were collected and histopathological findings of skin biopsy specimens were analyzed. RESULTS: All 3 patients had prior CLL and later developed cutaneous RS lesions. The mean age at the diagnosis of cutaneous RS was 67 years old. The time intervals between CLL and cutaneous RS were 3 to 8 years. Skin biopsy specimens demonstrated dermal nodular or perivascular infiltrates of large B cells, showing similar immunophenotypes to the lesional cells in the original CLL. Overexpression of p53 and positive stain for Epstein-Barr virus--encoded small RNA was found in one patient. One patient remained alive 8 years after the diagnosis whereas the other two died of the disease at 5 years and 3 weeks, respectively, after the onset of cutaneous RS. LIMITATIONS: Three patients with RS were followed up for up to 8 years. CONCLUSIONS: Our findings suggested that, in contrast to extracutaneous RS, cutaneous RS generally has a less aggressive course with longer survival unless other worse prognostic factors are present. PMID- 21982062 TI - In search of prognostic indicators for lymphomatoid papulosis: a retrospective study of 123 patients. AB - BACKGROUND: Lymphomatoid papulosis (LyP) is a benign recurrent papulonodular skin eruption with histologically malignant features that sometimes (10%-20%) progresses to lymphoma. OBJECTIVE: We retrospectively evaluated the clinical course of patients with LyP and identify prognostic factors possibly indicating a malignant course. METHODS: Clinical, histopathologic, and immunologic features and molecular genetics were examined and correlated with clinical course and outcomes. Immunophenotyping and chemokine profiling were performed in select skin biopsy samples. A follow-up questionnaire was sent to patients. Clinical course and association with neoplastic disorders were correlated with LyP subtypes, molecular genetics, and immunophenotyping studies. RESULTS: Of 123 patients with LyP (1991-2008) followed up a mean of 4 years (range, 2 months to 14 years), 17 (14%) had an associated hematologic malignancy, 8 of which were mycosis fungoides. Histopathologic analyses demonstrated classic LyP type A (n = 69), B (n = 13), or C (n = 6), and a slight predominance of T-cell CD8 marker expression for type A. More than one type of lesion was present in 9 patients with a higher incidence of hematologic malignancies. T-cell receptor gene rearrangement positivity was about two times higher, with LyP associated with hematologic malignancy (82% vs 44%; odds ratio 5.7; P = .02). Chemokine studies in a subset of 25 patients showed chemokine receptor (CCR) CCR4(+) and thymus and activation related chemokine (TARC(+)) in all LyP types and CCR3(+) and chemokine-related receptor (CXCR) CXCR3(+) in types B and C. LIMITATIONS: Retrospective study design is a limitation. CONCLUSIONS: Positive T-cell receptor gene rearrangement or diagnosis of mixed-type LyP may be a prognostic indicator of disease more prone to progress to lymphoma. PMID- 21982063 TI - Expression of innate defense antimicrobial peptides in hidradenitis suppurativa. AB - BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disorder of apocrine gland-bearing skin. It is associated with alterations in innate immunity and frequent bacterial infections. OBJECTIVE: We investigated the expression of innate defense antimicrobial peptides in patients with HS and different grades of severity. METHODS: Skin biopsy specimens and sweat were collected from 36 patients with HS and 57 healthy control subjects for analysis of epithelial antimicrobial peptides by real-time reverse transcription-polymerase chain reaction, immunohistochemistry, enzyme-linked immunosorbent assay, and surface enhanced laser desorption ionization time-of-flight mass spectrometry. RESULTS: We provide evidence that human beta-defensin-3 expression is induced in lesional HS skin on transcriptional and protein levels, yet, this up-regulation was not detectable in patients with severe HS (Hurley grade III). In contrast, messenger RNA expression of ribonuclease 7 was significantly diminished in lesional HS skin specimens irrespective of HS severity. Overall levels of dermcidin/dermcidin derived peptides in sweat and messenger RNA expression of psoriasin in skin biopsy specimens did not differ between patients with HS and healthy control subjects. LIMITATION: The relatively small number of samples, in particular in the group of patients with HS and Hurley grade III, is a limitation. CONCLUSION: Deficient constitutive production of ribonuclease 7 and, in severe HS, reduced human beta-defensin-3 induction may contribute to impaired immunity within the hair follicle and thereby boost HS inflammation and severity. PMID- 21982064 TI - MECP2 mutations and clinical correlations in Greek children with Rett syndrome and associated neurodevelopmental disorders. AB - BACKGROUND: Mutations in the MECP2 gene (methyl-CpG-binding protein-2) are responsible for 60-95% of cases of Rett syndrome (RTT), an X-linked dominant neurodevelopmental disorder affecting mostly girls. Classic RTT is characterized by normal early development followed by psychomotor regression and onset of microcephaly, although variant forms are also observed. MECP2 has also been implicated in variable mental retardation (MR) phenotypes, including X-linked Mental Retardation (XLMR), Fragile-X-like Syndrome (FXS) and Angelman-like (AS) phenotypes. AIM: The aim of the study was: (a) to evaluate the incidence and spectrum of MECP2 mutations in children with RTT and variant MR; (b) to evaluate phenotype-genotype correlations. METHODS: Exons 3-4 were analyzed for mutations in 281 MR patients (aged 13 months-27 years old, 144 males-137 females) consisting of 88 patients referred for RTT and 193 patients referred for AS-like and FXS-like types of MR. Statistical analysis included correlation between classic MECP2-positive and MECP2-negative and variant RTT patients, and frequency of MECP2 mutations in the various categories. RESULTS: Mutations were detected in ~ 70% of classic and ~ 21% of variant RTT, respectively. Amongst MR cases, 2.1% carried MECP2 mutations. MECP2-positive females had more problems in ambulation, muscle tone, tremor and ataxia, respiratory disturbances, head growth, hand use and stereotypies. Classic RTT-positive versus negative had significant respiratory and sitting problems and versus variant RTT-positive females ambulatory, hand and stereotypies problems. CONCLUSION: The analysis of the MECP2 gene could provide a diagnostic tool for RTT and non-specific MR research. PMID- 21982065 TI - Improving the clinical risk score: an analysis of molecular biomarkers in the era of modern chemotherapy for resectable hepatic colorectal cancer metastases. AB - BACKGROUND: The prognostic relevance of variations in expression of specific tumor genes in colorectal cancer liver metastases (CRCLMs) in patients treated with resection and modern chemotherapy is not known. METHODS: Patients submitted to liver resection for CRCLM between January 2000 and October 2007 were studied. A clinical risk score (CRS; range, 0-5) was calculated for each patient. RNA was extracted from histologically confirmed tumor isolates, and using real-time polymerase chain reaction (PCR) studies, we assessed the quantitative expression of 12 genes with potential importance in chemotherapy resistance and tumor progression, including thymidylate synthase (TS; 5-fluorouracil), excision repair cross complementing gene-1, and xeroderma pigmentosum groups A through G (oxaliplatin), topoisomerase-I (irinotecan), c-met, and hepatocyte growth factor. Primary outcomes were recurrence-free survival (RFS) and disease-specific survival (DSS) after hepatic resection. RESULTS: One-hundred fifty-five patients with good quality tumor mRNA were identified. Median follow-up was 32 months for survivors, and the median CRS was 2. Eighty-seven patients (56%) received preoperative chemotherapy, and 124 (80%) received postoperative chemotherapy. Median RFS for all patients was 13 months, and 3-year DSS was 69%. Median RFS and 3-year DSS for patients with an increased CRS (3-5) was lower (7 vs 18 months [P < .0001] and 50% vs. 80% [P < .0001], respectively). Of the 12 genes studied, only increased TS expression was associated with a lower RFS (hazard ratio, 1.16; 95% confidence interval, 1.0-1.3; P = .03) and DSS (hazard ratio, 1.25; 95% confidence interval, 1.0-1.5; P = .03). Median RFS and 3-year DSS for patients with increased TS expression was decreased (9 vs. 15 months [P = .03] and 48% vs. 82% [P = .001], respectively). TS expression had prognostic value that was independent of CRS on multivariate analysis. CONCLUSION: In patients with hepatic CRCLM treated with resection and modern chemotherapy, increased expression of TS improves outcome stratification and appears to be a useful biomarker. PMID- 21982066 TI - Pancreatic acinar cell carcinoma. PMID- 21982067 TI - Multidrug strategies are effective in the treatment of severe experimental pancreatitis. AB - BACKGROUND: Trypsinogen activation, oxygen radicals, cytokines, leukocyte infiltration, and pancreatic ischemia are important steps in the pathogenesis of necrotizing pancreatitis and associated systemic complications. Several drugs that inhibit those pathogenetic steps attenuated biochemical and histologic changes, while survival remained low. The aim of the present study was to evaluate the benefit of multidrug approaches compared to monotherapies on organ injury and survival in acute experimental pancreatitis in the rat model of retrograde bile injection combined with intravenous cerulein. METHODS: Necrotizing pancreatitis was induced in rats. After a therapy-free interval of 6 hours, 10 treatment regimens were evaluated: multidrug regimen 1, which contained the protease inhibitor gabexate mesilate, oxygen-free radical scavengers, nitric oxide donor L-arginine, a platelet-activating factor antagonist, and antibodies against intracellular adhesion molecule-1 (ICAM-1) dissolved in dextran, was compared to multidrug regimen 2 (dextran, acetylcysteine, L-arginine, and anti ICAM-1), monotherapies of each of the drugs, and standard intravascular volume replacement. RESULTS: Both multidrug regimens significantly reduced pancreatic and systemic injury and microcirculatory disturbances compared to any of the monotherapies. Treatment with regimen 1 decreased 24-hour mortality to 0% and increased long-term survival to 85% (standard therapy, 70% and 15%, respectively). Multidrug regimen 2 was as effective as regimen 1. CONCLUSION: Treatment of acute necrotizing pancreatitis with multidrug regimens significantly decreases short-term mortality compared to monotherapies. Moreover, multidrug strategies are still effective after a wide therapeutic window. Key to this effective therapy is the inhibition of microcirculatory disturbances and of the systemic inflammatory response. The experimental superiority of the multidrug approach should be confirmed in a clinical trial. PMID- 21982068 TI - Neutralization of interleukin-10 or transforming growth factor-beta decreases the percentages of CD4+ CD25+ Foxp3+ regulatory T cells in septic mice, thereby leading to an improved survival. AB - OBJECTIVES: To investigate the role of CD4+ CD25+ Foxp3+ regulatory T cells (Tregs) in septic conditions, and to examine the potential of targeting them for the treatment of sepsis. BACKGROUND: Sepsis-induced immunosuppression has long been considered a factor in late mortality of patients with sepsis. Although Tregs are central to the maintenance of immunologic homeostasis and tolerance, little is known about Treg-mediated immunosuppression in the late stages of sepsis. METHODS: Peripheral blood mononuclear cells (MNCs) in septic patients and liver or spleen MNCs collected after a cecal ligation and puncture (CLP) model in C57BL/6 mice were examined to evaluate the roles of Tregs and the correlation of transforming growth factor (TGF)-beta or interleukin (IL)-10 with their activity. We next examined the effects of neutralization of TGF-beta or IL-10 on the percentages of Tregs in CD4+ T cells and the survival rates of septic mice. RESULTS: The percentages of Tregs in peripheral blood lymphocytes were significantly increased in patients with sepsis, and there was a significantly positive correlation between serum IL-10 levels and the percentage of Tregs. CLP injury increases the percentages of Tregs in the CD4+ T cells in the spleen, and there was a significantly positive correlation between the percentages of Tregs and the serum IL-10 or TGF-beta levels. The neutralization of TGF-beta or IL-10 decreased the percentages of Tregs in CD4+ T cells, restored the percentages of CD4+ T cells in spleen MNCs, and improved survival rates in septic mice. CONCLUSION: We found an increase in the percentages of Tregs in peripheral blood circulating CD4+ T cells from patients with sepsis, and in splenic MNCs from septic mice, and observed that regulation of Tregs by neutralizing IL-10 or TGF beta might represent a novel strategy for treating the immunosuppressive conditions in sepsis. PMID- 21982069 TI - Segmental intestinal autotransplantation after extensive enterectomy for removal of large intra-abdominal desmoid tumors of the mesentery root: initial experience. PMID- 21982070 TI - Trainee satisfaction in surgery residency programs: modern management tools ensure trainee motivation and success. AB - OBJECTIVE: To assess trainee satisfaction in their surgery residency with a validated instrument and identify the contributing factors. BACKGROUND: Currently, surgery is deemed unattractive by medical students and ignored by many candidates planning to enter an academic career. New insights on the rational for such lack of interest are needed. Job satisfaction is a central concept in organizational and behavioral research that is well understood by large companies such as Google, IBM, and Toyota. Similar assessment can likewise be used to improve trainee satisfaction in surgery residency. METHODS: A survey among 2039 surgery residents was conducted in three European countries analyzing satisfaction at work using the Global Job Satisfaction Instrument (validated in Emergency Room physicians). Crucial factors covering different aspects of surgery residency where identified using the GJS instrument combined with multiple logistic regression analysis. RESULTS: With an overall response rate of 23%, we identified trainee dissatisfaction in one third of residents. Factors affecting satisfaction related almost exclusively to training issues, such as assignment of surgery procedures according to skills (OR 4.2), training courses (OR 2.7), availability of a structured training curriculum (OR 2.4), bedside teaching, and availability of morbidity-mortality conferences (OR 2.3). A good working climate among residents (OR 3.7) and the option for part time work (OR 2.1) were also significant factors for trainee satisfaction. Increased working hours had a modest (OR 0.98)-though cumulative- negative effect. The sex of the trainee was not related to trainee satisfaction. CONCLUSION: Validated measurement of job satisfaction as used in the industry appears to be an efficient tool to assess trainee satisfaction in surgery residency and thereby identify the key contributing factors. Improvement of conceptual training structures and working conditions might facilitate recruitment, decrease drop-out, and attract motivated candidates with possibly better quality of care. PMID- 21982071 TI - Robot-assisted laparoscopic ultrasonography for hepatic surgery. AB - INTRODUCTION: This study describes and evaluates a novel, robot-assisted laparoscopic ultrasonographic device for hepatic surgery. Laparoscopic liver surgery is being performed with increasing frequency. One major drawback of this approach is the limited capability of intraoperative ultrasonography (IOUS) using standard laparoscopic devices. Robotic surgery systems offer the opportunity to develop new tools to improve techniques in minimally invasive surgery. This study evaluates a new integrated ultrasonography (US) device with the da Vinci Surgical System for laparoscopic visualization, comparing it with conventional handheld laparoscopic IOUS for performing key tasks in hepatic surgery. METHODS: A prototype laparoscopic IOUS instrument was developed for the da Vinci Surgical System and compared with a conventional laparoscopic US device in simulation tasks: (1) In vivo porcine hepatic visualization and probe manipulation, (2) lesion detection accuracy, and (3) biopsy precision. Usability was queried by poststudy questionnaire. RESULTS: The robotic US proved better than conventional laparoscopic US in liver surface exploration (85% success vs 73%; P = .030) and tool manipulation (79% vs 57%; P = .028), whereas no difference was detected in lesion identification (63 vs 58; P = .41) and needle biopsy tasks (57 vs 48; P = .11). Subjects found the robotic US to facilitate better probe positioning (80%), decrease fatigue (90%), and be more useful overall (90%) on the post-task questionnaire. CONCLUSION: We found this robot-assisted IOUS system to be practical and useful in the performance of important tasks required for hepatic surgery, outperforming free-hand laparoscopic IOUS for certain tasks, and was more subjectively usable to the surgeon. Systems such as this may expand the use of robotic surgery for complex operative procedures requiring IOUS. PMID- 21982072 TI - Phenol procedure for pilonidal sinus disease and risk factors for treatment failure. AB - BACKGROUND: The present study was designed to evaluate the results of phenolization for pilonidal sinus disease and the risk factors for treatment failure. METHODS: Between June 2005 and July 2009, 76 consecutive patients with nonrecurrent sacrococcygeal pilonidal sinus were treated with a phenol treatment and included in the study. The clinical (age, sex, story of treatment for abscess formation, and comorbidity), operative (localization and number of sinus openings and volume of cavity), and follow-up data (healing time, time off work, postoperative complications, morbidity, and number of phenolization sessions) of the patients was recorded. Gender, age, history of abscess drainage, number of sinus openings, localization of sinus openings, volume of cavity, and the number of phenolization sessions were analyzed as risk factors for treatment failure. RESULTS: The overall success rate was 67% (51 of 76 patients). The mean time to complete healing was 16 days (range, 10-45). The time off work was 0 days. Age and gender were not found to be risk factors for treatment failure (P > .05 and P > .05, respectively). Patients with a history of abscess drainage and more than 3 sinus openings had a significantly higher risk of treatment failure (P = .001 and P = .046, respectively). There was no difference between the localization of sinus openings and treatment failure (P > .05). There were statistically significant differences between treatment failure and both the cavity volume and number of phenolization sessions (P = .016 and P = .001, respectively). Patients were followed up for a mean period of 25 months (range, 13-48). One patient (2%) showed recurrence. CONCLUSION: With an early return to work and low rates of complications and recurrence, phenolization is a simple outpatient procedure for the treatment of pilonidal sinus disease in selected patients. PMID- 21982073 TI - Use of omentum or falciform ligament does not decrease complications after pancreaticoduodenectomy: nationwide survey of the Japanese Society of Pancreatic Surgery. AB - BACKGROUND: Wrapping is thought to prevent pancreatic fistula and postoperative hemorrhage for pancreaticoduodenectomy (PD), and we analyzed whether omentum/falciform ligament wrapping decreases postoperative complications after PD. METHODS: This is a retrospective study of wrapping using the omentum/falciform ligament in patients that underwent PD between January 2006 and June 2008 in 139 institutions that were members of the Japanese Society of Pancreatic Surgery. RESULTS: Ninety-one institutions responded to the questionnaires, and data were accumulated from 3,288 patients. The data from 2,597 patients were acceptable for analysis; 918 (35.3%) patients underwent wrapping and 1,679 patients did not. A pancreatic fistula occurred in 623 patients (37.3%) in the nonwrapping group, in comparison to 393 patients (42.8%) in the wrapping group (P = .006). The incidence of a grade B/C pancreatic fistula was lower in the nonwrapping group than the wrapping group (16.7% vs. 21.5%; P = .002). An intra-abdominal hemorrhage occurred in 54 patients (3.2%) in the nonwrapping group, which was similar to the incidence in the wrapping group (32 patients; 3.5%). The mortality was 1.3% and 1.0% in nonwrapping and wrapping groups, respectively. A multivariate analysis revealed 7 independent risk factors for pancreatic fistula; male, hypoalbuminemia, soft pancreas, long operation time, extended resection, pylorus preservation, and omentum wrapping. There were 4 independent risk factors for early intra-abdominal hemorrhage and 2 independent risk factors for late intra-abdominal hemorrhage. CONCLUSION: This retrospective study revealed that omentum wrapping did not decrease the incidence of pancreatic fistula. An additional validation study is necessary to evaluate the efficacy of wrapping for PD. PMID- 21982074 TI - Modulating vagal signaling in abdominal surgery. PMID- 21982075 TI - Associations between promoter polymorphism -106A/G of interleukin-11 receptor alpha and papillary thyroid cancer in Korean population. AB - BACKGROUND: The interleukin11 (IL11) and IL11 receptor alpha (IL11RA) are involved in cellular growth, differentiation, invasiveness, and tumor progression in several tumors. We investigated whether coding single nucleotide polymorphisms (cSNPs) of IL11 and promoter SNP IL11RA would contribute to the development of papillary thyroid cancer (PTC). We also assessed the relationships between IL11 and IL11RA SNPs and the clinicopathologic characteristics of PTC. METHODS: One coding SNP, designated as rs1126757, Ala82Ala, in IL11 and one promoter SNP, designated as rs1061758, -106A/G, in IL11RA were genotyped using direct sequencing in 94 patents with PTC and 213 patients without PTC (controls). Genetic data were analyzed using commercially available software. The patients with PTC were dichotomized and compared with respect to clinicopathologic characteristics of PTC. RESULTS: We found an association between PTC and the coding SNP(rs1061758) in IL11RA (codominant model 1 [G/G vs. A/G], odds ratio [OR] = 2.91, 95% confidence interval [CI], 1.44-5.89; P = .003; codominant model 2 [G/G vs. A/A], OR = 2.95, 95% CI, 1.30-6.72; P = .01; and dominant model, OR = 2.92, 95% CI, 1.47-5.80; P = .002). Moreover, SNP rs1061758 in IL11RA was associated with the multifocality of PTC (codominant model 2 [A/A vs. G/G], OR = 9.56, 95% CI, 1.77-51.69; P = .009; and recessive model, OR = 7.22, 95% CI, 1.72 30.3; P = .007). Genotype and allele analyses of SNP variant rs1126757 in IL11 revealed no statistically significant differences between patients with PTC and controls. CONCLUSION: Our results suggest that an IL11RA promoter polymorphism- rs1061758--may be associated with the risk of PTC in the Korean population. In addition, rs1061758 might be related to the multifocality of PTC. PMID- 21982076 TI - Hearing loss in children with mitochondrial disorders. AB - OBJECTIVE: At least 1-5 children per 1000 suffer from congenital hearing loss, and 50% of these cases can be attributed to genetic causes. It has been estimated that 1% of pre-lingual hearing loss is due to mutations in mitochondrial DNA. Previous literature reports audiometric data for few patients, usually less than 20 per study. The goal of this study was to characterize the hearing loss associated with mitochondrial mutations and determine whether previously characterized patterns of hearing loss in these patients (progressive, sensorineural, high frequency losses) are found in our population as well. METHODS: An IRB-approved retrospective chart review of the electronic medical records in the Nemours/Alfred I. dupont Hospital for Children system from January 2004 to October 2009 (a five-year period) was undertaken using ICD-9 codes 277.87 (mitochondrial disorder) and 359.89BA (mitochondrial myopathy). These 149 records were then evaluated for audiologic data, resulting in 26 charts with both a mitochondrial disorder and hearing evaluation. RESULTS: Of 26 patients with known mitochondrial disorders and audiometric documentation, 15 (58%) had hearing loss, and 11 patients had normal hearing (42%). Ten patients had sensorineural hearing loss (38%), two patients had conductive hearing loss (7.7%), one patient had a mixed hearing loss (3.8%), and two patients had an as yet undefined hearing loss (ABR had not yet been performed at the time of this study) (7.7%). CONCLUSION: In comparison with previous studies, generally including less than 20 patients, this is one of the largest collections of audiometric data on children with mitochondrial disorders. Unlike prior studies describing a progressive, sensorineural loss across all frequencies or mainly affecting high frequencies, the hearing loss in our patients was more variable including low frequency losses, mid-frequency losses, and conductive losses and was often not progressive or even improved. Our overall 38% rate of sensorineural hearing loss correlates well with previous case series; this study clearly justifies the use of routine audiometric screening in children with mitochondrial disorders, including use of ABR and OAEs as ASND can be seen in this population, as well as repeat testing over time to evaluate for progression. PMID- 21982077 TI - Comparison of learning preferences of Turkish children who had been applied cochlear implantation in Turkey and Germany according to theory of multiple intelligence. AB - AIM: The aim of the study is to determinate the using dominant multiple intelligence types and compare the learning preferences of Turkish cochlear implanted children aged four to ten in Turkey and Germany according to Theory of multiple intelligence. MATERIAL AND METHOD: The study has been conducted on a total of 80 children and four groups in Freiburg/Germany and Ankara/Turkey. The applications have been done in University of Freiburg, Cochlear Implant Center in Germany, and University of Hacettepe, ENT Department, Audiology and Speech Pathology Section in Turkey. In this study, the data have been collected by means of General Information Form and Cochlear Implant Information Form applied to parents. To determine the dominant multiple intelligence types of children, the TIMI (Teele Inventory of Multiple Intelligences) which was developed by Sue Teele have been used. RESULTS: The study results exposed that there was not a statistically significant difference on dominant intelligence areas and averages of scores of multiple intelligence types in control groups (p>0.05). Although, the dominant intelligence areas were different (except for first dominant intelligence) in cochlear implanted children in Turkey and Germany, there was not a statistically significant difference on averages of scores of dominant multiple intelligence types. CONCLUSION: Every hearing impaired child who started training, should be evaluated in terms of multiple intelligence areas and identified strengths and weaknesses. Multiple intelligence activities should be used in their educational programs. PMID- 21982078 TI - Laryngotracheal reconstruction in infants and children: are single-stage anterior and posterior grafts a reliable intervention at all pediatric hospitals? AB - OBJECTIVE: To review outcomes of pediatric laryngotracheal stenosis treated by single-stage laryngotracheal reconstruction with anterior and posterior cartilage grafts and compare decannulation rate for single-stage laryngotracheal reconstruction with rates published at larger (>200 beds) pediatric tertiary care hospitals. METHODS: A 4-year retrospective chart review (2004-2008) of all patients undergoing procedures coded with 2008 CPT codes 31582 (laryngoplasty for laryngeal stenosis with graft or core mold, including tracheotomy) and 31587 (laryngoplasty, cricoid split) for a pediatric, tertiary-care hospital. Interventions were single-stage laryngotracheal reconstruction with anterior and posterior cartilage grafts, and the main outcome measure was the decannulation rate after single-stage laryngotracheal reconstruction. RESULTS: We identified 44 patients with subglottic stenosis, of whom 13 underwent single-stage laryngotracheal reconstruction with anterior and posterior cartilage grafts. The mean age at surgery was 2.2 years (range, 5 months to 4 years). Twelve of 13 children had Cotton-Myer grade III stenosis. Ninety-two percent (12 of 13) of children remain decannulated. The mean follow up was 52 months. CONCLUSIONS: Single-stage laryngotracheal reconstruction with anterior and posterior cartilage grafts appears to be a safe and effective technique for managing patients with high-grade subglottic stenosis at intermediate size children's hospitals. Our overall decannulation rate of 92% compares favorably to that reported in the literature (84-96%). PMID- 21982079 TI - Hearing impairment in otitis media with effusion: a cross-sectional study based in Pokhara, Nepal. AB - OBJECTIVE: Otitis media with effusion (OME) is a major cause of childhood hearing impairment (HI) in the developing world, but its prevalence has never been quantified in Nepal. This study therefore set out to determine the proportion of cases of OME complicated by HI and to identify associated factors. METHODS: This was a cross-sectional prevalence survey carried out in rural, urban and Tibetan schools in and around Pokhara, Nepal. HI was the primary outcome, and was defined as a middle-frequency pure tone average >25 dB on audiological testing. The study population was defined as children aged four years and older, attending primary school and with a diagnosis of OME. RESULTS: One hundred and eleven schoolchildren with a combined total of 172 ears affected by OME underwent audiometric assessment. HI was most prevalent in the rural Nepali population; 27% (95%CIs 18-38%) had HI, with a mean hearing loss of 22 dB (15-25 dB). In the Tibetan population, 16% (8-29%) had HI, with a mean loss of 17 dB (12-22 dB). The urban Nepali population had the least HI; 4% (1-13%) were affected, with a mean loss of 16 dB (15-19 dB). The difference in prevalence between the urban and rural Nepali populations was statistically significant (p>0.05). Logistic regression analysis did not identify any associated factors. CONCLUSIONS: HI is a common complication of OME in Nepal. There is hitherto-unreported variation between populations in the number of cases of OME complicated by HI. This study identified higher rates of morbidity amongst rural populations but was unable to identify associated factors. PMID- 21982081 TI - Gradual improvement in fine-grained sensitivity to triadic gaze after 6 years of age. AB - The current research compared the ability of adults and children to determine where another person is looking in shared visual space (triadic gaze). In Experiment 1, children (6-, 8-, 10-, and 14-year-olds) and adults viewed photographs of a model fixating a series of positions separated by 1.6 degrees along the horizontal plane. The task was to indicate whether the model was looking to the left or right of one of three target positions (midline, 6.4 degrees left, or 6.4 degrees right). By 6 years of age, thresholds were quite small (M=1.94 degrees ) but were roughly twice as large as those of adults (M=1.05 degrees ). Thresholds decreased to adult-like levels around 10 years of age. All age groups showed the same pattern of higher sensitivity for central targets than peripheral targets and of misjudging gaze toward peripheral targets as farther from midline than it really was. In subsequent experiments, we evaluated possible reasons for the higher thresholds in 6- and 8-year-olds. In Experiment 2, the thresholds of 6-year-olds did not improve when the range of deviations from the target position that the model fixated covered a much wider range. In Experiment 3, 8-year-olds were less sensitive than adults to small shifts in eye position even though the task required only matching faces with the same eye position and not determining where the person was looking. These findings suggest that by 6 years of age, children are quite sensitive to triadic gaze, which may support inferences about others' interests and intentions. Subsequent improvements in sensitivity involve, at least in part, an increase in sensitivity to eye position. PMID- 21982082 TI - Rediscovering the Americas. PMID- 21982080 TI - Automated 4D analysis of dendritic spine morphology: applications to stimulus induced spine remodeling and pharmacological rescue in a disease model. AB - Uncovering the mechanisms that regulate dendritic spine morphology has been limited, in part, by the lack of efficient and unbiased methods for analyzing spines. Here, we describe an automated 3D spine morphometry method and its application to spine remodeling in live neurons and spine abnormalities in a disease model. We anticipate that this approach will advance studies of synapse structure and function in brain development, plasticity, and disease. PMID- 21982083 TI - It's time to kill this Bill. PMID- 21982084 TI - Early child development-a winning combination. PMID- 21982085 TI - NCDs: celebrating success, moving forward. PMID- 21982086 TI - Diabetes-call for papers. PMID- 21982088 TI - Jacques Miller: immunologist who discovered role of the thymus. PMID- 21982089 TI - Medical schools in sub-Saharan Africa. PMID- 21982090 TI - A new era for global tuberculosis control. PMID- 21982091 TI - A new era for global tuberculosis control. PMID- 21982092 TI - Medical schools in sub-Saharan Africa. PMID- 21982093 TI - Medical schools in sub-Saharan Africa. PMID- 21982095 TI - Networking request from a pharmaceutical company? PMID- 21982096 TI - Multiple rejections: role of the writing process. PMID- 21982097 TI - Maculopapular lesions in the Central African Republic. PMID- 21982098 TI - Early non-adherence to medication and other risk factors for rehospitalization in schizophrenia and schizoaffective disorder. AB - Non-adherence to antipsychotic medication and hospitalization in psychotic disorders are common and costly problems. Our aim was to identify risk factors for rehospitalization of patients with recent onset schizophrenia or schizoaffective disorder in a population-based cohort study. All patients with a first hospitalization for schizophrenia or schizoaffective disorder between 2006 and 2007 were included (n = 861). Patients were identified through and data retrieved from national Swedish health and population registers. We investigated how socio-demographic variables, duration of first hospitalization and prescription fills of antipsychotics were associated with rehospitalization in Cox regression models. A higher risk for rehospitalization within 28 days was observed in patients with a first hospitalization that was shorter than two weeks compared with patients who were hospitalized for more than four weeks: hazard ratio (HR) 2.30, 95% confidence interval (CI) 1.42 to 3.74. Further, patients who did not fill a prescription of antipsychotics within the first week after discharge had a higher risk of early rehospitalization than patients who were given antipsychotics (HR 1.75, 95% CI 1.13 to 2.72). More than 12 years of education was associated with a lower risk of early rehospitalization (HR 0.44, 95% CI 0.26 to 0.77). Sex, age, being born in Sweden, urban area residence and prescription fills of antipsychotics prior to first admission did not significantly affect the risk of early rehospitalization. In conclusion, we identified two potentially modifiable risk factors for rehospitalization: short duration of initial hospitalization and early non-adherence to medication. PMID- 21982099 TI - Characteristic higher-order aberrations of the anterior and posterior corneal surfaces in 3 corneal transplantation techniques. AB - PURPOSE: To investigate the corneal higher-order aberrations (HOAs) of the anterior and posterior corneal surfaces in eyes that underwent penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK), and Descemet stripping automated endothelial keratoplasty (DSAEK). DESIGN: Retrospective, case control study. METHODS: study population: Twenty-four eyes underwent PK, 28 eyes underwent DALK, and 19 eyes underwent DSAEK; 29 normal eyes served as controls. observation procedures: The anterior and posterior corneal heights and pachymetric data were obtained with a Scheimpflug-based corneal topographer. Corneal HOAs for 4-mm pupils were calculated from the height data and were expanded with normalized Zernike polynomials. The HOAs resulting from the anterior and posterior corneal surfaces were compared among the procedures. main outcome measures: Anterior and posterior corneal HOAs (root mean square). RESULTS: Control eyes had significantly lower total HOAs and Zernike vector terms of the anterior and posterior surfaces than the other groups, except for spherical aberration. The mean anterior corneal surface total HOAs in the PK, DALK, DSAEK, and control groups were 1.38 +/- 0.67 MUm, 1.19 +/- 0.57 MUm, 0.61 +/- 0.33 MUm, and 0.21 +/- 0.07 MUm, respectively. The anterior corneal HOAs in the DSAEK group were significantly less than those in the PK group (P < .001) and DALK group (P < .001). The mean posterior corneal surface total HOAs were, respectively, 0.20 +/- 0.09 MUm, 0.24 +/- 0.11 MUm, 0.27 +/- 0.15 MUm, and 0.07 +/- 0.02 MUm. There were no significant differences in the posterior corneal HOAs among the treatment groups. CONCLUSIONS: Because the refractive indices between the anterior and the posterior surfaces differed greatly, eyes that undergo DSAEK have lower anterior corneal HOAs compared with PK or DALK eyes. However, the anterior and posterior corneal HOAs in DSAEK eyes still were greater than those in control eyes. PMID- 21982100 TI - Recent statin use and cataract surgery. AB - PURPOSE: To investigate whether the statin class of drugs reduces the risk of cataract extraction. DESIGN: Case-control study. METHOD: setting: Kaiser Permanente Southern California, which provides prepaid healthcare for 3.2 million residents by 6000 physicians. patient population: Eligible patients were those who had 5+ years of continuous enrollment in 2009. Cases were 13 982 patients who underwent cataract surgery in their first eye in 2009. Controls were the 34 049 patients who had an eye examination, but did not undergo cataract surgery or have a diagnosis of cataract in their medical record. observation procedure: The primary source of data to assess cataract surgery, treatment with statins, and other risk factors is the electronic database of Kaiser Permanente. main outcome measure: Use of the statin class of drug. RESULTS: Patients who had cataract surgery were older, were more likely to be white, and appeared to have more coronary artery disease but less diabetes. The proportion of statin users appeared to be greater among those with cataract surgery (64.3%) compared to those without a diagnosis of cataract or cataract surgery (55.5%). After adjustment for age, sex, race, smoking status, diabetes, and coronary artery disease, longer-term statin use was found to be protective against cataract extraction (OR: 0.93, P = .02), while shorter-term use was associated with cataract surgery (OR: 1.11, P < .0001). Age-stratified logistic regression analysis showed that statin use of 5 years or more was protective against cataract surgery in the younger age group (50-64 years), while shorter-term use (<5 years) was associated with an increased risk of surgery in both the younger and older age groups (60+ years). CONCLUSION: The current study finds that recent longer-tem statin use was protective against cataract surgery in younger patients (50-64 years of age), while shorter-term use was associated with an increased risk of surgery. One strength of the current study is information on the large number of incident cases of cataract extraction and the electronic database on drug use. Additional studies will be needed to understand the difference in effect between longer- and shorter-term users of statins. PMID- 21982101 TI - Ocular complications of human immunodeficiency virus infection in eastern china. AB - PURPOSE: To investigate ocular complications in patients with HIV/AIDS in eastern China during the time of highly active antiretroviral therapy (HAART). DESIGN: Prospective study. METHODS: This study was carried out from August 1, 2009 to July 31, 2010. Recruited HIV/AIDS patients underwent a series of surveys and ophthalmologic and laboratory examinations (including CD4 level) at enrollment. RESULTS: In this study, all 787 HIV/AIDS patients (1574 eyes) had a history of HAART. Of these patients, 28.72% (95% CI = 0.26-0.32) had a history of systemic disease and 26.30% (95% CI = 0.23-0.29) had ocular complications. Of these ocular complications, cytomegalovirus retinitis (CMVR) had the highest prevalence (10.6%, 83/787) and ocular microangiopathy had the second-highest prevalence (9.4%, 74/787). Among the patients with CMVR, 16.9% (14/83) suffered from immune recovery uveitis (IRU). Furthermore, 3.4% (27/787) of the recruited AIDS patients had neuro-ophthalmologic disorders. The mean logMAR visual acuity of the group with ocular complications was 0.47 +/- 0.64, which was significantly different from the asymptomatic group (0.17 +/- 0.39, P < .001). The median CD4 T-cell count of the group with ocular complications is 43 cells/MUL, which was significantly different from the asymptomatic group (116.5 cells/MUL, P < .001). CONCLUSIONS: The study shows a high rate of treatable ocular complications among patients with HIV/AIDS in eastern China. HIV/AIDS treatment programs in China must be prepared to identify ocular complications and refer patients to the correct treatment facilities. PMID- 21982102 TI - Punctal and canalicular anatomy: implications for canalicular occlusion in severe dry eye. AB - PURPOSE: To characterize the microscopic anatomy of the lacrimal punctum and canaliculi in relation to the tarsal plate, muscle of Riolan, and Horner muscle; and to report a novel technique to excise the horizontal canaliculus in severe dry eye patients. DESIGN: Observational anatomic study and a retrospective case series. METHODS: The microscopic anatomy was studied in 86 eyelids of 25 cadavers (age range: 45-96 years, mean: 79.5 years). Surgery was performed on 18 canaliculi of 7 patients with dry eyes (age range: 37-69 years, mean: 59.9 years). In the microscopic study, 32 eyelids were incised sagittally, 38 eyelids were incised horizontally (1 mm from the eyelid margin), and 16 eyelids were incised parallel to the tarsal plate. All specimens were stained with Masson trichrome. In the surgical group, probe-guided horizontal canalicular excision with incision of the Horner muscle to the lateral edge of the lacrimal caruncle was performed. Both canalicular stumps were cauterized. RESULTS: In the microscopic anatomic study, the punctum and the vertical canaliculus were part of the tarsal plate with the muscle of Riolan, whereas the horizontal canaliculus was surrounded by the Horner muscle. In the surgical group, all the operated canaliculi were completely occluded without recanalization 12 months postoperatively. No complications were recorded. CONCLUSIONS: Based on microscopic anatomic findings that the lacrimal punctum and the vertical canaliculus are part of the tarsal plate, and that the horizontal canaliculus is surrounded by the Horner muscle, excision of the horizontal canaliculus may be an effective technique to treat patients with severe dry eyes. PMID- 21982103 TI - The long-term survival analysis of bilateral lateral rectus recession versus unilateral recession-resection for intermittent exotropia. AB - PURPOSE: To conduct a comparison of the long-term surgical outcomes of bilateral lateral rectus recession (BLR) vs unilateral lateral rectus recession-medial rectus resection (RR) in treatment of intermittent exotropia. DESIGN: Nonrandomized, retrospective case series. METHODS: Consecutive patients who underwent BLR or RR for treatment of intermittent exotropia between 2002 and 2006 and had >=2 years' follow-up were recruited. Surgical outcomes were grouped according to postoperative angle of deviation as overcorrection (esophoria/tropia >5 Delta), success (esophoria/tropia <=5 Delta to exophoria/tropia <=10 Delta), or undercorrection/recurrence (exophoria/tropia >10 Delta), and were compared between the BLR group and the RR group at postoperative 1 day, 1 month, 6 months, 1 year, and 2 years, and at the final examination. RESULTS: Of 128 patients, 55 underwent BLR and 73 underwent RR. The mean follow-up period was 44.2 months in the BLR group and 47.8 months in the RR group. At 1 day, 1 month, 6 months, 1 year, and 2 years after surgery, surgical outcomes in each group were not different (P > .05) However, the final outcome at a mean of 3.8 years was significantly different between the groups, demonstrating a higher success rate in the BLR group than in the RR group (58.2% vs 27.4%, P < .01). Cumulative probability of survival from recurrence was higher in the BLR group than in the RR group (P = .01, log-rank test). Recurrences were most common within 6 months from surgery; however, after that, recurrences occurred continuously in the RR group and rarely in the BLR group. CONCLUSION: Surgical outcomes by 2 years after surgery for intermittent exotropia were not different between the BLR and RR groups. However, final outcomes were better in the BLR group than in the RR group. This may be caused by the difference of recurrence rate over time: continuous recurrence of exotropia occurred in the RR group, while recurrence was low in the BLR group after postoperative 6 months. PMID- 21982104 TI - Clinicopathologic and immunohistochemical features of pigmented Basal cell carcinomas of the eyelids. AB - PURPOSE: To describe the clinical and microscopic features of pigmented basal cell carcinomas (pBCC) of the eyelid. DESIGN: Retrospective observational case series collected at one institution. METHODS: An analysis of clinical records, photographs, and histopathologic characteristics of 257 BCCs with a review of the literature. The frequencies of clinically pigmented, and of microscopically pigmented but clinically nonpigmented, BCCs were determined. Cytochemical stains (Fontana-Masson, Prussian blue) and immunohistochemical probes (S-100, microphthalmia-associated transcription factor [MiTF], HMB-45, MART-1, CK20, synaptophysin, chromogranin, CD1a, Ki-67) were then employed and the findings correlated with the degree of clinical pigmentation. RESULTS: Histopathologically, 13 of 257 cases (5.06%) were found to have pigment; of these 13, 6 (all white patients) had clinically apparent pigmentation (2.33%), either focal or diffuse. Eight of 13 lesions developed on the lower eyelids. All stained positively for melanin but negatively for iron. MiTF highlighted numerous melanocytic nuclei in the tumor lobules, while MART-1 and HMB-45 revealed the dendritic shapes of the entrapped melanocytes. There was a subtotal blockage of melanin transfer to the surrounding basaloid cells. Intralobular S-100-positive cells included CD1a-positive Langerhans cells, while CK20 did not identify any Merkel cells. CONCLUSIONS: Only 1 of 6 lesions was uniformly clinically pigmented, whereas the other 5 were only focally brown-black. The clinical pigmentation was imparted by varying densities and distributions of melanocytes with arborizing dendrites, which were present in all BCCs. Melanophages within the stroma and basaloid cell melanization also contributed to pigmentation. No behavioral or biologic differences in pBCC were documented compared with clinically nonpigmented lesions. PMID- 21982105 TI - Prediction of postoperative eyelid height after frontalis suspension using autogenous fascia lata for pediatric congenital ptosis. AB - PURPOSE: To predict eyelid height after frontalis suspension using autogenous fascia lata for congenital ptosis. DESIGN: Retrospective, observational case series. METHODS: Eighty eyes of 54 children who underwent frontalis suspension using autogenous fascia lata were included. The amount of intraoperative eyelid lift and the postoperative change in eyelid height were assessed 6 months after surgery by reviews of photographs and medical records. The amount of operative eyelid lift was measured from 2 different baselines, and each amount was compared with the amount of real change in eyelid height after surgery. The difference between those was measured. RESULTS: The postoperative eyelid height stabilized 3 months after surgery. The average amount of operative eyelid lift was 5.91 mm with anesthesia-induced lagophthalmos and 3.51 mm without. The amount of real change in eyelid height after surgery was 3.24 +/- 1.14 mm. In less severe ptosis (< 3 mm of lift), an average operative lift of 2.03 mm resulted in 2.53 mm of elevation, whereas in more severe ptosis (>= 4 mm of lift), an average operative lift of 3.98 mm resulted in only 3.72 mm of elevation 6 months after surgery. The preoperative palpebral fissure (P = .002) and anesthesia-induced lagophthalmos (P < .001) were significant factors influencing postoperative eyelid height. CONCLUSIONS: Postoperative eyelid height may predicted be more accurately by compensating for anesthesia-induced lagophthalmos and adjusting the palpebral fissure to be larger than the desired eyelid height for patients with more severe ptosis. PMID- 21982106 TI - Subconjunctival bevacizumab versus mitomycin C adjunctive to trabeculectomy. AB - PURPOSE: To compare the outcome of trabeculectomy with subconjunctival bevacizumab with that of trabeculectomy with mitomycin C (MMC). DESIGN: Prospective, randomized, comparative study. METHODS: Thirty-six eyes from 34 patients with uncontrolled glaucoma were enrolled. Eighteen eyes underwent trabeculectomy with subconjunctival bevacizumab injection (2.5 mg/0.1 mL), and 18 eyes underwent trabeculectomy with MMC (0.02% for 3 minutes). The outcome measures were the best-corrected visual acuity, intraocular pressure (IOP), number of IOP-lowering medications, complications, and bleb morphologic features (based on the Indiana Bleb Appearance Grading Scale). RESULTS: The mean follow-up times for the MMC and bevacizumab groups were 7.8 +/- 2.2 months and 7.4 +/- 24 months, respectively (P = .62). The mean preoperative IOP in the bevacizumab group improved from 21.9 +/- 7.9 mm Hg with 2.7 +/- 0.8 antiglaucoma medications to 13.6 +/- 3.2 mm Hg with 0.2 +/- 0.5 antiglaucoma medications at the last visit (P < .001 and P < .001, respectively). The mean preoperative IOP in the MMC group improved from 23.3 +/- 4.9 mm Hg with 2.6 +/- 0.7 antiglaucoma medications to 9.6 +/- 2.7 mm Hg with no antiglaucoma medications at the final visit (P < .001 and P < .001, respectively). There was a statistically significant difference in the IOP between the 2 groups at the last visit (P < .001). The cumulative probabilities of total success at the last follow-up according to Kaplan-Meier analysis were 100% and 94.4% in bevacizumab and MMC groups, respectively (P = .32, log-rank test). CONCLUSIONS: Adjunctive subconjunctival bevacizumab with trabeculectomy is effective in controlling the IOP profile; however, its effect is less prominent than that of MMC. PMID- 21982107 TI - Vascular endothelial growth factor in plasma and vitreous fluid of patients with proliferative diabetic retinopathy patients after intravitreal injection of bevacizumab. AB - PURPOSE: To investigate plasma and vitreous vascular endothelial growth factor (VEGF) levels after intravitreal bevacizumab (IVB) injection into eyes with proliferative diabetic retinopathy (PDR). DESIGN: Retrospective, interventional, nonrandomized, comparative study. METHODS: Fifty-six eyes of 56 patients with PDR and 13 eyes of 13 patients with nondiabetic ocular diseases were enrolled. Analysis included evaluation of basic clinical conditions and measurement of vitreous and plasma VEGF concentrations using enzyme-linked immunosorbent assays. RESULTS: PDR eyes without IVB had the highest vitreous VEGF levels; the levels were significant compared with those in the recent IVB group (previous injection within 1 week), the prolonged IVB group (injection more than 1 week previously), and the nondiabetic control group (P = .001, P = .035, P < .001, respectively). The vitreous VEGF level in the recent IVB group was higher than that in prolonged IVB group (P = .035). PDR eyes without IVB had the highest plasma VEGF level, and the level was significant compared with those in the recent IVB group, the prolonged IVB group, and the nondiabetic control group (P < .001, P = .003, P < .001, respectively). The plasma VEGF level in the recent IVB group was lower than that in the prolonged IVB group (P = .003). The vitreous VEGF level was associated significantly with the plasma VEGF level (P = .002). CONCLUSIONS: Vitreous and plasma VEGF levels were increased markedly in patients with PDR. VEGF concentrations in vitreous and plasma were decreased significantly after IVB into PDR eyes, and the effect lasted from 4.4 +/- 2.2 days to 34.8 +/- 33.7 days after injection. PMID- 21982108 TI - Risk factors for orbital exenteration in periocular Basal cell carcinoma. AB - PURPOSE: To present the proportion of patients with periocular basal cell carcinoma (BCC) who underwent orbital exenteration and to evaluate the significance of the following risk factors: initial tumor site, pathologic features, and initial treatment. DESIGN: Retrospective, comparative, interventional case series. METHODS: Charts of all patients with BCC referred to Orbital Unit of the University of Naples "Federico II" between 1984 and 2003 were reviewed. Charts were reviewed for patient demographics, previous treatments, tumor site, clinical presentation, duration of symptoms, and histologic subtype. The main outcomes were recurrence rate, tumor-related deaths, orbital infiltration, and rate of exenteration. RESULTS: Data (including follow-up) were available for 506 patients. Twenty-eight patients (5.5%) underwent orbital exenteration. For 8 patients (28.5%), orbital exenteration was the first procedure performed. In the exenterated group, the most common tumor site was the medial cantus, whereas in the overall group, it was the lower eyelid (P = .001). The proportion of patients initially treated without margin control was significantly higher in patients undergoing exenteration (P = .0001). Pathologic examination revealed a higher incidence of infiltrative subtype in the exenterated group (P = .00019). CONCLUSIONS: The need for exenteration for BCC may be significantly higher when the lesion involves a medial canthal location, initial management does not include margin-controlled excision, or pathologic analysis reveals an infiltrative subtype. Margin-controlled excision for periocular BCC and close follow-up after excision for medial canthal BCC may be indicated. PMID- 21982109 TI - Intravitreal bevacizumab for treatment of subfoveal idiopathic choroidal neovascularization: results of a 1-year prospective trial. AB - PURPOSE: To evaluate the visual and anatomic outcomes of intravitreal bevacizumab in patients with subfoveal idiopathic choroidal neovascularization (CNV). DESIGN: Prospective, nonrandomized, interventional case series. METHODS: Forty patients with subfoveal idiopathic CNV were included in this clinical trial. Their eyes were treated with a single intravitreal injection of 1.25 mg bevacizumab followed by as-needed dosing indicated by the presence and recurrence of intraretinal edema, subretinal fluid (SRF), or pigment epithelial detachment (PED), based on optical coherence tomography (OCT) performed monthly. Visual, clinical, angiographic, and anatomic changes were observed over a 12-month follow-up period. RESULTS: After 12 months of follow-up, the mean logarithm of minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA) improved from 0.53 (20/68 in Snellen equivalent) at baseline to 0.29 (20/39 in Snellen equivalent; P < .001). Mean central retinal thickness determined by OCT decreased from 321 MUm to 237 MUm (P < .001). All eyes (100%) had stable or improved vision, and 28 eyes (70%) showed an improvement of 2 lines or more. All lesions were in the cicatricial stage of CNV at 12 months of follow-up, with no leakage of fluorescein in the late phase of fluorescein angiography and no intraretinal edema, SRF, and/or PED detected by OCT. No drug-related systemic or ocular side effects were observed. CONCLUSIONS: Intravitreal bevacizumab is generally well tolerated and improves BCVA in eyes with subfoveal idiopathic CNV over a period of 12 months. Large, randomized, controlled, long-term clinical trials are required to further evaluate the efficacy and optimal strategy of this treatment modality. PMID- 21982110 TI - Prevalence, progression, and impact of glaucoma on vision after Boston type 1 keratoprosthesis surgery. AB - PURPOSE: To report glaucoma outcomes after Boston type 1 keratoprosthesis (KPro) surgery, in particular, glaucoma prevalence, progression, and treatment. DESIGN: Consecutive, retrospective, interventional case series. METHODS: setting: Tertiary care institution. study population: Thirty-eight eyes in 38 patients. intervention: KPro surgery. main outcome measures: Visual acuity (VA), intraocular pressure, visual fields, optic nerve status, and glaucoma treatment. RESULTS: Glaucoma diagnosis was known before surgery in 29 patients (76%; 14 had undergone previous surgery) and was diagnosed after surgery in 34 patients (89%) after a mean +/- standard deviation of 16.5 +/- 4.7 months of follow-up. The number of patients taking intraocular pressure-lowering medications increased from 19 (50%) before surgery to 28 (76%) after surgery (P = .017). Twenty-four patients (63%) were taking at least 1 additional glaucoma medication at their most recent postoperative visit. Eight patients (21%) had glaucoma progression (visual field progression, need for surgery, or both). Fifteen patients (40%) had a cup-to-disc ratio of 0.85 or more. Five patients required glaucoma surgery. VA was limited by glaucoma in 14 patients (37%), 11 of whom had a VA of 20/200 or worse. Five such patients (13%) had a dramatic improvement in VA, then progressed to end-stage glaucoma with fixation loss. Visual fields were limited by glaucoma in 25 patients (66%; mean Swedish Interactive Threshold Algorithm Fast mean defect, -20.3 +/- 8.8 decibels; n = 18). CONCLUSIONS: Most KPro candidates have glaucoma, which may deteriorate in a subset of patients after surgery. Dramatic VA improvement after KPro surgery does not preclude the need for rigorous monitoring for glaucoma progression. A low threshold should be used to treat suspicion of even slightly elevated intraocular pressure. PMID- 21982111 TI - Vascular endothelial-cadherin: a possible link between endocytosis and ectodomain shedding. PMID- 21982113 TI - Inflammation-mediated upregulation of centrosomal protein 110, a negative modulator of ciliogenesis, in patients with chronic rhinosinusitis. AB - BACKGROUND: Sinonasal mucosa in patients with chronic rhinosinusitis (CRS) is often devoid of motile cilia. This defect is presumed to result from prolonged inflammation, infection, or both. However, the mechanism underlying this observation is unknown. Recently, centrosomal protein 110 (Cp110) was shown to prevent the terminal step in ciliary maturation (ie, elongation), suggesting that Cp110 might be involved in pathological states in which ciliation is abnormal. OBJECTIVES: First, we sought to investigate the expression of Cp110 in sinonasal mucosa from patients with CRS and control subjects. Second, we sought to determine the extent that inflammatory cytokines modulate Cp110 expression and ciliary maturation in vitro. METHODS: Sinonasal mucosal specimens from patients with and without CRS were analyzed for Cp110 mRNA and protein expression. Furthermore, human and murine nasal respiratory epithelial cultures were used to investigate Cp110 expression under normal growth conditions and in the presence of exogenous proinflammatory cytokines. RESULTS: Increased Cp110 mRNA and protein expression was found in sinonasal mucosal specimens from patients with CRS compared with that seen in control specimens. During ciliogenesis in vitro, the expression of Cp110 gradually decreased in cultures derived from patients without CRS but remained increased in cultures derived from patients with CRS. Furthermore, cultures grown in the presence of proinflammatory cytokines demonstrated increased levels of Cp110 expression with concomitant inhibition of ciliogenesis. CONCLUSION: Increased Cp110 expression in mucosa from patients with CRS might contribute to the poor ciliation observed in patients with CRS. Exogenous cytokine exposure maintains increased levels of Cp110 expression. Regulation of Cp110 expression by inflammation warrants additional investigation because it might offer a novel target in the management of respiratory tract diseases. PMID- 21982115 TI - Drug hypersensitivity reactions: Inconsistency in the use of the classification of immediate and nonimmediate reactions. PMID- 21982116 TI - Effects of olanzapine on muscarinic M3 receptor binding density in the brain relates to weight gain, plasma insulin and metabolic hormone levels. AB - The second generation antipsychotic drug (SGA) olanzapine has an efficacy to treat schizophrenia, but can cause obesity and type II diabetes mellitus. Cholinergic muscarinic M3 receptors (M3R) are expressed on pancreatic beta-cells and in the brain where they influence insulin secretion and may regulate other metabolic hormones via vagal innervation of the gastrointestinal tract. Olanzapine's M3R antagonism is an important risk factor for its diabetogenic liability. However, the effects of olanzapine on central M3Rs are unknown. Rats were treated with 0.25, 0.5, 1.0 or 2.0 mg olanzapine/kg or vehicle (3*/day, 14 days). M3R binding densities in the hypothalamic arcuate (Arc) and ventromedial nuclei (VMH), and dorsal vagal complex (DVC) of the brainstem were investigated using [3H]4-DAMP plus pirenzepine and AF-DX116. M3R binding correlations to body weight, food intake, insulin, ghrelin and cholecystokinin (CCK) were analyzed. Olanzapine increased M3R binding density in the Arc, VMH and DVC, body weight, food intake, circulating plasma ghrelin and CCK levels, and decreased plasma insulin and glucose. M3R negatively correlated to insulin, and positively correlated to ghrelin, CCK, food intake and body weight. Increased M3R density is a compensatory up-regulation in response to olanzapine's M3R antagonism. Olanzapine acts on M3R in regions of the brain that control food intake and insulin secretion. Olanzapine's M3R blockade in the brain may inhibit the acetylcholine pathway for insulin secretion. These findings support a role for M3Rs in the modulation of insulin, ghrelin and CCK via the vagus nerve and provide a mechanism for olanzapine's diabetogenic and weight gain liability. PMID- 21982117 TI - Alteration in RGS2 expression level is associated with changes in haloperidol induced extrapyramidal features in a mutant mouse model. AB - Antipsychotic induced Parkinsonism (AIP) is a common adverse effect of antipsychotic drug treatment among schizophrenia patients. Two previous studies showed association of the rs4606 SNP in the 3' untranslated region of the regulator of G protein signaling 2 gene (RGS2) with susceptibility to AIP. Since rs4606 reportedly influences expression of RGS2, we applied a translational approach and studied the effect of chronic (24 days) exposure to haloperidol on AIP-like features in mice carrying a mutation that causes lower Rgs2 gene expression. Haloperidol and vehicle treated male mice heterozygous (HET) or homozygous (HOM) for the mutation, or wild type (WT), were evaluated for open field locomotion, catalepsy duration, pole test performance and rota-rod latency to fall. We showed that in haloperidol treated mice lower Rgs2 expression is associated with better performance on the open field, catalepsy and rota-rod tests but not the pole test. Results were most consistent for the 0.2 mg/kg/d haloperidol dose. These observations support the possible involvement of RGS2 in mechanisms underlying susceptibility to AIP. PMID- 21982118 TI - Characterisation and manipulation of docetaxel resistant prostate cancer cell lines. AB - BACKGROUND: There is no effective treatment strategy for advanced castration resistant prostate cancer. Although Docetaxel (Taxotere(r)) represents the most active chemotherapeutic agent it only gives a modest survival advantage with most patients eventually progressing because of inherent or acquired drug resistance. The aims of this study were to further investigate the mechanisms of resistance to Docetaxel. Three Docetaxel resistant sub-lines were generated and confirmed to be resistant to the apoptotic and anti-proliferative effects of increasing concentrations of Docetaxel. RESULTS: The resistant DU-145 R and 22RV1 R had expression of P-glycoprotein and its inhibition with Elacridar partially and totally reversed the resistant phenotype in the two cell lines respectively, which was not seen in the PC-3 resistant sublines. Resistance was also not mediated in the PC-3 cells by cellular senescence or autophagy but multiple changes in pro- and anti-apoptotic genes and proteins were demonstrated. Even though there were lower basal levels of NF-kappaB activity in the PC-3 D12 cells compared to the Parental PC-3, docetaxel induced higher NF-kappaB activity and IkappaB phosphorylation at 3 and 6 hours with only minor changes in the DU-145 cells. Inhibition of NF-kappaB with the BAY 11-7082 inhibitor reversed the resistance to Docetaxel. CONCLUSION: This study confirms that multiple mechanisms contribute to Docetaxel resistance and the central transcription factor NF-kappaB plays an immensely important role in determining docetaxel-resistance which may represent an appropriate therapeutic target. PMID- 21982119 TI - Emergency department triage: an ethical analysis. AB - BACKGROUND: Emergency departments across the globe follow a triage system in order to cope with overcrowding. The intention behind triage is to improve the emergency care and to prioritize cases in terms of clinical urgency. DISCUSSION: In emergency department triage, medical care might lead to adverse consequences like delay in providing care, compromise in privacy and confidentiality, poor physician-patient communication, failing to provide the necessary care altogether, or even having to decide whose life to save when not everyone can be saved. These consequences challenge the ethical quality of emergency care. This article provides an ethical analysis of "routine" emergency department triage. The four principles of biomedical ethics - viz. respect for autonomy, beneficence, nonmaleficence and justice provide the starting point and help us to identify the ethical challenges of emergency department triage. However, they do not offer a comprehensive ethical view. To address the ethical issues of emergency department triage from a more comprehensive ethical view, the care ethics perspective offers additional insights. SUMMARY: We integrate the results from the analysis using four principles of biomedical ethics into care ethics perspective on triage and propose an integrated clinically and ethically based framework of emergency department triage planning, as seen from a comprehensive ethics perspective that incorporates both the principles-based and care-oriented approach. PMID- 21982120 TI - Complementary and alternative medicine for patients with chronic fatigue syndrome: a systematic review. AB - BACKGROUND: Throughout the world, patients with chronic diseases/illnesses use complementary and alternative medicines (CAM). The use of CAM is also substantial among patients with diseases/illnesses of unknown aetiology. Chronic fatigue syndrome (CFS), also termed myalgic encephalomyelitis (ME), is no exception. Hence, a systematic review of randomised controlled trials of CAM treatments in patients with CFS/ME was undertaken to summarise the existing evidence from RCTs of CAM treatments in this patient population. METHODS: Seventeen data sources were searched up to 13th August 2011. All randomised controlled trials (RCTs) of any type of CAM therapy used for treating CFS were included, with the exception of acupuncture and complex herbal medicines; studies were included regardless of blinding. Controlled clinical trials, uncontrolled observational studies, and case studies were excluded. RESULTS: A total of 26 RCTs, which included 3,273 participants, met our inclusion criteria. The CAM therapy from the RCTs included the following: mind-body medicine, distant healing, massage, tuina and tai chi, homeopathy, ginseng, and dietary supplementation. Studies of qigong, massage and tuina were demonstrated to have positive effects, whereas distant healing failed to do so. Compared with placebo, homeopathy also had insufficient evidence of symptom improvement in CFS. Seventeen studies tested supplements for CFS. Most of the supplements failed to show beneficial effects for CFS, with the exception of NADH and magnesium. CONCLUSIONS: The results of our systematic review provide limited evidence for the effectiveness of CAM therapy in relieving symptoms of CFS. However, we are not able to draw firm conclusions concerning CAM therapy for CFS due to the limited number of RCTs for each therapy, the small sample size of each study and the high risk of bias in these trials. Further rigorous RCTs that focus on promising CAM therapies are warranted. PMID- 21982121 TI - High-grade mitral valve insufficiency after fracture of the Mitrofix prosthesis. PMID- 21982122 TI - Three years after SYNTAX trial--change in practice? PMID- 21982124 TI - Pacific climate variability and the possible impact on global surface CO2 flux. AB - BACKGROUND: Climate variability modifies both oceanic and terrestrial surface CO2 flux. Using observed/assimilated data sets, earlier studies have shown that tropical oceanic climate variability has strong impacts on the land surface temperature and soil moisture, and that there is a negative correlation between the oceanic and terrestrial CO2 fluxes. However, these data sets only cover less than the most recent 20 years and are insufficient for identifying decadal and longer periodic variabilities. To investigate possible impacts of interannual to interdecadal climate variability on CO2 flux exchange, the last 125 years of an earth system model (ESM) control run are examined. RESULTS: Global integration of the terrestrial CO2 flux anomaly shows variation much greater in amplitude and longer in periodic timescale than the oceanic flux. The terrestrial CO2 flux anomaly correlates negatively with the oceanic flux in some periods, but positively in others, as the periodic timescale is different between the two variables. To determine the spatial pattern of the variability, a series of composite analyses are performed. The results show that the oceanic CO2 flux variability peaks when the eastern tropical Pacific has a large sea surface temperature anomaly (SSTA). By contrast, the terrestrial CO2 flux variability peaks when the SSTA appears in the central tropical Pacific. The former pattern of variability resembles the ENSO-mode and the latter the ENSO-modoki1. CONCLUSIONS: Our results imply that the oceanic and terrestrial CO2 flux anomalies may correlate either positively or negatively depending on the relative phase of these two modes in the tropical Pacific. PMID- 21982123 TI - Multi-modal registration of speckle-tracked freehand 3D ultrasound to CT in the lumbar spine. AB - A method for registration of speckle-tracked freehand 3D ultrasound (US) to preoperative CT volumes of the spine is proposed. We register the US volume to the CT volume by creating individual US "sub-volumes", each consisting of a small section of the entire US volume. The registration proceeds incrementally from the beginning of the US volume to the end, registering every sub-volume, where each sub-volume contains overlapping images with the previous sub-volume. Each registration is performed by generating simulated US images from the CT volume. As a by-product of our registration, the significant drift error common in speckle-tracked US volumes is corrected for. Results are validated through a phantom study of plastic spine phantoms created from clinical patient CT data as well as an animal study using a lamb cadaver. Results demonstrate that we were able to successfully register a speckle-tracked US volume to CT volume in four out of five phantoms with a success rate of greater than 98%. The final error of the registered US volumes decreases by over 50 percent from the speckle tracking error to consistently below 3 mm. Studies on the lamb cadaver showed a mean registration error consistently below 2 mm. PMID- 21982126 TI - The antiviral activity of six South African plants traditionally used against infections in ethnoveterinary medicine. AB - Viral infections remain a major threat to humans and animals and there is a crucial need for new antiviral agents especially with the development of resistant viruses. The hexane, dichloromethane, acetone and methanol extracts of six plant species selected for their traditional use against infections were tested for in vitro antiviral activity against canine distemper virus (CDV), canine parainfluenza virus-2 (CPIV-2), feline herpesvirus-1 (FHV-1) and lumpy skin disease virus (LSDV). All extracts were tested for their cytotoxicity using a colorimetric tetrazolium-based (MTT) assay and were tested for antiviral efficacy at concentrations below CC(50) values on the various cell types used in this study. The antiviral activity of extracts was tested using virucidal and attachment assays. In the virucidal assay, extracts were incubated with virus prior to infection. The most potent inhibition was observed with the acetone and methanol extracts of Podocarpus henkelii against CDV and LSDV, which inhibited replication of the viruses by >75% at 3MUg/ml with selectivity index (SI) values ranging between 12 and 45. Excellent activity was also found with the hexane extracts of Plumbago zeylanica and Carissa edulis against CDV, with the extracts reducing viral-induced CPE by 50% and 75% respectively. The hexane extract of C. edulis had moderate activity against FHV-1 with EC(50)<70MUg/ml and SI value <2. Only the acetone extract of P. henkelii moderately inhibited replication of LSD virus in the attachment assay, with low activity in other extracts. Of the four extracts with significant antiviral activity, two were prepared from P. henkelii. Therefore, future work will focus on isolating and characterizing the substance(s) responsible for bioactivity in extracts of this species. PMID- 21982125 TI - Neuropathogenesis of a highly pathogenic avian influenza virus (H7N1) in experimentally infected chickens. AB - In order to understand the mechanism of neuroinvasion of a highly pathogenic avian influenza virus (HPAIV) into the central nervous system (CNS) of chickens, specific pathogen free chickens were inoculated with a H7N1 HPAIV. Blood, cerebrospinal fluid (CSF), nasal cavity and brain tissue samples were obtained from 1 to 4 days post-inoculation (dpi) of infected and control chickens. Viral antigen topographical distribution, presence of influenza A virus receptors in the brain, as well as, the role of the olfactory route in virus CNS invasion were studied using different immunohistochemistry techniques. Besides, viral RNA load in CSF and blood was quantified by means of a quantitative real-time reverse transcription-polymerase chain reaction. Viral antigen was observed widely distributed in the CNS, showing bilateral and symmetrical distribution in the nuclei of the diencephalon, mesencephalon and rhombencephalon. Viral RNA was detected in blood and CSF at one dpi, indicating that the virus crosses the blood CSF-barrier early during infection. This early dissemination is possibly favoured by the presence of Siaalpha2,3 Gal and Siaalpha2,6 Gal receptors in brain vascular endothelial cells, and Siaalpha2,3 Gal receptors in ependymal and choroid plexus cells. No viral antigen was observed in olfactory sensory neurons, while the olfactory bulb showed only weak staining, suggesting that the virus did not use this pathway to enter into the brain. The sequence of virus appearance and the topographical distribution of this H7N1 HPAIV indicate that the viral entry occurs via the haematogenous route, with early and generalized spreading through the CSF. PMID- 21982127 TI - Transmission characteristics of low pathogenic avian influenza virus of H7N7 and H5N7 subtypes in layer chickens. AB - Low pathogenic avian influenza virus (LPAIv) infections of H5 and H7 subtypes in poultry are notifiable to the OIE, hence surveillance programmes are implemented. The rate at which LPAIv strains spread within a flock determines the prevalence of infected birds and the time it takes to reach that prevalence and, consequently, optimal sample size and sampling frequency. The aim of this study was to investigate the transmission characteristics of an H7N7 and an H5N7 LPAIv in layer chickens. Two transmission experiments were performed, which consisted of 30 (first experiment) and 20 (second experiment) pairs of conventional layers, respectively. At the start of the experiments, one chicken per pair was inoculated with LPAIv and the other chicken was contact-exposed. Occurrence of infection was monitored by regularly collecting tracheal and cloacal swab samples, which were examined for the presence of virus RNA by RT-PCR. The results of the test were used to estimate the transmission rate parameter (beta), the infectious period (T) and the basic reproduction ratio (R(0)). In addition, egg production and virus shedding patterns were quantified. For the H7N7 virus, the beta, T and R(0) estimates were 0.10 (95% confidence interval (CI): 0.04-0.18) day(-1), 7.1 (95% CI: 6.5-7.8) days and 0.7 (95% CI: 0.0-1.7), respectively. With the H5N7 virus, only a few inoculated chickens (5 out of 20) became infected and no transmission was observed. This study shows that transmission characteristics of LPAIv strains may vary considerably, which has to be taken into account when designing surveillance programmes. PMID- 21982128 TI - Determinants of cardiovascular and all-cause mortality in northwest Russia: a 10 year follow-up study. AB - PURPOSE: To study conventional and novel risk factors associated with high cardiovascular disease (CVD) and all-cause mortality in Russia. METHODS: A prospective cohort study of 3704 adults was performed in Arkhangelsk. The baseline examination was conducted in 1999-2000. The average follow-up was 10.2 years. Information on lifestyle and marital, educational, and psychosocial status was self-reported in a questionnaire. Data on risk factors were collected in a medical examination that included the drawing of blood samples. RESULTS: By October 2010 a total of 147 male and 95 female deaths had occurred. In 59 male and 20 female deaths in which a diagnosis was made by a forensic pathologist, the autopsy data were studied to extract information on post-mortem blood alcohol concentration. A positive blood alcohol concentration was found in 21 (36%) male and 6 (30%) female forensic autopsies. Women reporting consumption of at least 80 g of alcohol monthly and consumption of 5 or more alcohol units during one drinking episode had a greater risk of cardiovascular death than abstainers; relative risk (RR) was 5.06 (95% confidence interval [95% CI], 1.54-16.7) and 3.21 (95% CI, 1.07-9.58), respectively. ApoB/ApoA1-ratio was the strongest predictor of CVD and all-cause death in men (RR, 7.62; 95% CI, 3.15-18.4; and RR, 4.39; 95% CI, 2.22-8.68, respectively) and CVD death in women (RR 3.12; 95% CI, 1.08-8.98). Men who were obese and had obtained a university education had a 40% lower risk of all-cause death. Low serum albumin was associated with high mortality in both genders. CONCLUSIONS: Hazardous alcohol consumption is an independent risk factor of CVD mortality in women. The mechanisms behind its damaging effect are not yet clear. Nutritional factors such as serum albumin are important predictors of all-cause mortality in both genders. PMID- 21982129 TI - Validation of the normalized difference vegetation index as a measure of neighborhood greenness. AB - PURPOSE: To assess the validity of a Geographic Information Systems (GIS) measure, the Normalized Difference Vegetation Index (NDVI), as a measure of neighborhood greenness for epidemiologic research. METHODS: Using remote-sensing spectral data, NDVI was calculated for a 100-m radial distance around 124 residences in greater Seattle. The criterion standard was rating of greenness for corresponding residential areas by 3 environmental psychologists. Pearson correlations and regression models were used to assess the association between the psychologists' ratings of greenness and NDVI. Analyses were also stratified by residential density to assess whether the correlations differed between low and high density. RESULTS: The mean NDVI among this sample of residences was 0.27 (standard deviation [SD], 0.11; range, -0.04 to 0.54), and the mean psychologist rating of greenness was 2.84 (SD, 0.98; range, 1-5). The correlation between NDVI and expert ratings of greenness was high (r = 0.69). The correlation was equivalently strong within each strata of residential density. CONCLUSIONS: NDVI is a useful measure of neighborhood greenness. In addition to showing a strong correlation with expert ratings, this measure has practical advantages, including availability of data and ease of application to various boundaries, which would aid in replication and comparability across studies. PMID- 21982130 TI - The need to include the subject of natural remedies in midwifery education. PMID- 21982131 TI - The role of naturopathy in pregnancy, labour and post-natal care: broadening the evidence-base. AB - It is known that women are high users of complementary and alternative medicine (CAM) including naturopathy and that CAM is frequently used by pregnant women. However, we still know little about the consumption, practice and role of naturopathy in pregnancy, labour and post-natal care. With this in mind, this paper proposes a possible framework for advancing further research on this topic. The framework is divided into issues associated with three core stakeholder groups - pregnant women, naturopaths/herbalists and other maternity health professionals including obstetricians, midwives and general practitioners. The development of a rigorous health services research agenda around this topic has much to offer maternity-care users, practitioners and policy makers and the framework outlined here is offered with the hope of inspiring further inquiry into this significant issue in women's health. PMID- 21982132 TI - Exploring the impact of osteopathic treatment on cranial asymmetries associated with nonsynostotic plagiocephaly in infants. AB - OBJECTIVES: To document the evolution of cranial asymmetries in infants with signs of nonsynostotic occipital plagiocephaly (NSOP) who were to undergo a course of four osteopathic treatments (in addition to the standard positioning recommendations) as well as to determine the feasibility of using this methodology to conduct a randomized clinical trial investigating the impact of osteopathic intervention for infants with NSOP. DESIGN: Pilot clinical standardization project using pre-post design in which 12 infants participated. Ten infants presented an initial Oblique Diameter Difference Index (ODDI) over 104% and five of them had an initial moderate to severe Cranial Vault Asymmetry (CVA) (over 12mm). INTERVENTIONS: Infants received four osteopathic treatments at 2-week intervals. MAIN OUTCOME MEASURES: Anthropometric, plagiocephalometric as well as qualitative measures were administered pre-intervention (T1), during the third treatment (T2) and two weeks after the fourth treatment (T3). RESULTS: Participants showed a significant decrease in CVA (p=0.02), Skull Base Asymmetry (SBA) (p=0.01), Trans-Cranial Vault Asymmetry (TCVA) (p<0.003) between the first and third evaluations. CONCLUSIONS: These clinical findings support the hypothesis that osteopathic treatments contribute to the improvement of cranial asymmetries in infants younger than 6.5 months old presenting with NSOP characteristics. PMID- 21982133 TI - Complementary and alternative medicine (CAM) among hospitalised patients: reported use of CAM and reasons for use, CAM preferred during hospitalisation, and the socio-demographic determinants of CAM users. AB - PURPOSE: This paper reports a study to examine hospitalised patients' frequency and patterns of CAM use, their reasons for CAM use, their preferences of CAMs during hospitalisation, and the association between patients' socio-demographic variables and use of each individual CAM/CAM domain. METHODS: A convenience sample of 353 patients hospitalised in 19 surgical wards at four metropolitan hospitals completed a questionnaire on CAM use and socio-demographic variables. RESULTS: The response rate was 73.5%, and over 90% of the sample acknowledged using CAMs. Non-herbal supplements (60.3%) and massage therapy (45%) were the most frequently used CAMs, with biologically based therapies (68.8%) as well as mind-body interventions (65.4%) being the most often used CAM domains. About 1 in 10 patients (9.6%) used CAMs from all five domains. With the exception of herbal botanical therapies, self-prayer for health reasons/spiritual healing and music therapy, all CAMs were mainly used on an 'only when needed' basis. The most common reason nominated for using CAMs was that '[it] fits into my way of life/philosophy' (26%). The majority of patients declared interest in and support for the hospital providing CAMs. Patients were most inclined to choose therapies categorised as manipulative and body-based methods (65.4%) for use in hospital. Massage therapy (53.5%) and non-herbal supplements (43.1%) were the top two CAMs favoured for use in hospital. CAM use was also dependent of socio-demographic data (age, gender, marital status, place of residence, education level, religion, and income in hospitalised patients). CONCLUSION: The use of CAMs is pervasive amongst surgical in-patients, making it feasible to initially assess these patients for CAM use and provide them with clinically approved CAMs where possible. Notwithstanding that CAM use is fairly predictable by socio-demographic variables, further studies should be directed to know the variables useful for predicting the use of each CAM approach. PMID- 21982134 TI - Complementary medicine use is not associated with non-adherence to conventional medication in the elderly: a retrospective study. AB - Lack of adherence to medications is a potential cause of hospitalizations, morbidity, and mortality in the elderly. Medication adherence decreases with polypharmacy. Older persons commonly use complementary medicine, therefore complementary medicine use might pose an increase risk of loss of medication adherence with conventional medications, but this has not been previously investigated. A chart review was conducted of 300 patients at least sixty-five years of age who used at least three medications each who attended a university geriatrics clinic in Florida, USA to obtain information about medication adherence and complementary medicine use. However, no association was found between use of at least one complementary medicine and adherence to conventional medications. PMID- 21982135 TI - Pilot study: retreat intervention predicts improved quality of life and reduced psychological distress among breast cancer patients. AB - PURPOSE: Evaluate the effectiveness of a week-long residential retreat intervention incorporating photographic art therapy in concert with psychoanalytically oriented group therapy and mind-body practices in reducing psychological distress and improving quality of life (QoL) and spiritual well being for breast cancer patients. METHODS: 28 female breast cancer patients completed self report assessments of psychological distress, QoL, and spiritual well-being on the first day of the retreat, the last day of the retreat, and a 6 week follow up assessment. RESULTS: Repeated measures MANOVA with Bonferroni post hoc comparisons revealed the retreat experience to predict significant and sustained reductions in depression, anxiety, and somatic stress, coupled with sustained improvements in QoL and spiritual well-being. CONCLUSIONS: The current findings suggest that breast cancer patients may benefit from participation in a week-long multi-modal retreat center experience involving photographic art therapy and structured group therapy as a means to explore personal strain. PMID- 21982136 TI - The efficacy of lavender oil on perineal trauma: a review of the evidence. AB - Anecdotal evidence suggests that some women find lavender oil effective at relieving some of the symptoms associated with perineal trauma following childbirth. This paper examines the literature detailing the efficacy of lavender oil in wound care in an attempt to place these findings into the context of perineal trauma. The discussion and findings may assist midwives to proceed in a more informed manner in the absence of scientific evidence to underpin the practice of lavender oil use in the perineal context. PMID- 21982137 TI - Patients' views of CAM as spiritual practice. AB - OBJECTIVES: This paper explores Danish cancer patients' narratives on spiritual beliefs, practices and the relationship these practices may have to complementary and alternative medicine (CAM). DESIGN: Narrative inquiry was used to understand how spiritual beliefs and practices might be related to CAM. Thirty-two cancer patients, family, friends and alternative practitioners were followed up over a two year period by face to face interview, telephone and focus groups. RESULTS: Although religious and spiritual issues were not manifestly expressed by many of the subjects, these issues were significantly elaborated upon in narratives by four female participants to warrant more detailed consideration and analysis. CONCLUSION: It is suggested that for some cancer patients CAM may function, not just as a treatment for cancer related symptoms and side effects, but also as a form of spiritual practice. For some individuals a belief in the 'spiritual' role of CAM per se may be analogous to religious belief. PMID- 21982138 TI - Hand pain is reduced by massage therapy. AB - METHODS: Forty-six adults with hand pain were randomly assigned to a massage therapy or a standard treatment control group. Those assigned to the massage therapy group were massaged by a therapist on the affected hand once a week for a 4-week period and were also taught self-massage on the hand that was to be done by the individual participant once daily. RESULTS: The massage therapy group versus the control group had less pain and greater grip strength after the first and last sessions, and their anxiety and depressed mood scores decreased more than the control group. Over the four-week period the massage group had a greater decrease in pain and a greater increase in grip strength as well as lower scores on anxiety, depressed mood and sleep disturbance scales. PMID- 21982139 TI - The use of complementary and alternative medicine by patients with cancer: in Turkey. AB - This research sought to assess the use of complementary and alternative therapies (CAM) amongst Turkish patients with cancer. The research sample included 94 adult patients with cancer who underwent chemotherapy at an outpatient clinic at the Adult Oncology Department of the University of Izmir between November 2006 and January 2007. Data was collected by questionnaire. Results suggest that the majority of Turkish oncology patients in the study had used herbal essences or herbal therapies. Socio-demographic factors associated with CAM use considered gender, age, education and economic status, health insurance, and whether CAM use had been recommended by friends, health care professionals or others. There appeared to be a link between CAM use, the diagnosis of cancer and where patients lived (p < 0.05). Patients reported that their primary sources of CAM information for use with their medical condition had come from friends and the media. Patients tended to use CAM therapies to reduce some of the physical symptoms of their condition and particular side effects arising from their medical treatment. PMID- 21982140 TI - Herbal preparation use by patients suffering from cancer in Palestine. AB - This study sought to describe type, frequency, purpose and patterns of herbal medicine used by a sample of patients with cancer in Palestine. A cross-sectional survey of patients attending the outpatient cancer departments at the Governmental Hospitals was undertaken using semi-structured questionnaires. RESULTS: A total of 1260 patients with cancer were interviewed. Of the participants, 60.9% (n = 767) reported using herbs primarily bought from Palestine (92.3%) frequently employed in the form of decoctions (43%). The most common herbal product was Arum palaestinum (22.5%). Most Complementary and Alternative (CAM) users were more than 40 years of age, predominantly female, and living in rural areas of Palestine. Family member's recommendation was cited as the main factor prompting participants to use CAM (43.5%). CONCLUSION: This study revealed that there is an appreciable prevalence of herbal use among patients with cancer in Palestine. PMID- 21982141 TI - Meditation for the management of adjustment disorder anxiety and depression. AB - OBJECTIVE: To examine the effect of Meditation training on patients with adjustment disorder with anxiety and depression. METHOD: In a pre-test/post-test control group design, patients (N = 30) with adjustment disorder with mixed anxiety and depression, were screened through a Clinical Global Impression severity/Improvement Scale, Beck's Anxiety, Beck's Depression Inventory, and Global Assessment of Functioning. Sessions of meditation training (28 weeks) were held using the model of Yoga Meditation. The difference of means (pre- and post assessment) was tested using a paired t-test method. RESULTS: Experimental group and control groups were similar at base line, whereas after concluding the 28th week of meditation practice a significant mean difference (t value: CGI-S 2.47 > .05; CGI-I2.82 > 0.05; BAI 17.58 > 0.05; BDI 10.13 > 0.05; GAF 12.29 > 0.05) was found between both groups. There was an incremental change in selected assessment parameters in both groups. But changes were more significant in pre- and post assessment of experimental group. PMID- 21982142 TI - Pluripotency factor binding and Tsix expression act synergistically to repress Xist in undifferentiated embryonic stem cells. AB - BACKGROUND: Expression of Xist, the master regulator of X chromosome inactivation, is extinguished in pluripotent cells, a process that has been linked to programmed X chromosome reactivation. The key pluripotency transcription factors Nanog, Oct4 and Sox2 are implicated in Xist gene extinction, at least in part through binding to an element located in Xist intron 1. Other pathways, notably repression by the antisense RNA Tsix, may also be involved. RESULTS: Here we employ a transgene strategy to test the role of the intron 1 element and Tsix in repressing Xist in ES cells. We find that deletion of the intron 1 element causes a small increase in Xist expression and that simultaneous deletion of the antisense regulator Tsix enhances this effect. CONCLUSION: We conclude that Tsix and pluripotency factors act synergistically to repress Xist in undifferentiated embryonic stem cells. Double mutants do not exhibit maximal levels of Xist expression, indicating that other pathways also play a role. PMID- 21982143 TI - Implementation and outcomes of a hospital-wide computerised antimicrobial stewardship programme in a large medical centre in Taiwan. AB - Antibiotic stewardship is important to address the problem of antimicrobial resistance, but a practical and sustainable strategy to provide stewardship in a large hospital setting is lacking. We developed a hospital-wide computerised antimicrobial approval system (HCAAS) to guide the use of antimicrobial agents in late 2004 in a 3500-bed medical centre in Taiwan. The objective of this study was to evaluate the impacts of HCAAS on the hospital from 2003 to 2009. Following HCAAS deployment, the gradients of consumption over time during the study period of third- and fourth-generation cephalosporins, fluoroquinolones and glycopeptides fell significantly, whilst that of carbapenems increased. The amount and expenditure of antimicrobial use did not increase with the overall healthcare-associated infection rate, and inpatient mortality rate remained stable with a slight decreasing trend. The rate of meticillin-resistant Staphylococcus aureus started to decline in 2002 and continued after HCAAS deployment. There was an increasing isolation of extended-spectrum beta-lactamase producing Escherichia coli and Klebsiella pneumoniae, presumably leading to the increased use of carbapenems. The isolation rate of Clostridium difficile from patients who developed diarrhoea after antimicrobial therapy did not change over the years, with a mean annual rate of 10.0% after the implementation of HCAAS. HCAAS along with strict infection control measures is necessary to reduce the spread of resistant organisms within the hospital. HCAAS is a sustainable system for providing antibiotic stewardship and exerts a positive impact on the hospital by reducing antimicrobial consumption and expenditure whilst not compromising healthcare quality. PMID- 21982144 TI - Comparative randomised clinical trial against glycopeptides supports the use of daptomycin as first-line treatment of complicated skin and soft-tissue infections. PMID- 21982145 TI - Overexpression of the quorum-sensing regulator sdiA and soxS is involved in low level multidrug resistance induced in Escherichia coli AG100 by haloperidol, diazepam and NaCl. PMID- 21982146 TI - A stable phage lysin (Cpl-1) dimer with increased antipneumococcal activity and decreased plasma clearance. AB - Bacteriophages (phages) produce endolysins (lysins) as part of their lytic cycle in order to degrade the peptidoglycan layer of the infected bacteria for subsequent release of phage progeny. Because these enzymes maintain their lytic and lethal activity against Gram-positive bacteria when added extrinsically to the cells, they have been actively exploited as novel anti-infectives, sometimes termed enzybiotics. As with other relatively small peptides, one issue in their clinical development is their rapid inactivation through proteolytic degradation, immunological blockage and renal clearance. The antipneumococcal lysin Cpl-1 was shown to escape both proteolysis and immunological blockage. However, its short plasma half-life (20.5 min in mice) may represent a shortcoming for clinical usefulness. Here we report the construction of a Cpl-1 dimer with a view to increasing both the antipneumococcal specific activity and plasma half-life of Cpl-1. Dimerisation was achieved by introducing specific cysteine residues at the C-terminal end of the enzyme, thus favouring disulphide bonding. Compared with the native monomer, the constructed dimer demonstrated a two-fold increase in specific antipneumococcal activity and a ca. ten-fold decrease in plasma clearance. As several lysins are suspected to dimerise on contact with their cell wall substrate to be fully active, stable pre-dimerised enzymes may represent a more efficient alternative to the native monomer. PMID- 21982147 TI - Genetic response of Salmonella enterica serotype Enteritidis to thioridazine rendering the organism resistant to the agent. AB - Thioridazine (TZ)-induced accumulation of the universal efflux pump substrate ethidium bromide and its subsequent efflux by Salmonella strains with various degrees of overexpressed efflux pumps takes place automatically at pH 7.4, is independent of a metabolic source, is not affected by a proton ionophore and is precluded by palmitic acid. Salmonella enterica serotype Enteritidis cultured in medium containing increasing concentrations of TZ does not grow during the first 6-8h, after which time its growth is similar to unexposed controls. At the end of a 16-h exposure period, the organism is resistant to >250mg/L TZ. Parallel assessment by real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) of the activity of genes that regulate and code for the AcrB transporter of the main efflux pump (AcrAB) of the organism at periodic intervals suggests a sequence of activation beginning with the stress gene soxS, followed by the global regulator ramA, then by the local regulator marA and then by the transporter acrB. These activations take place during the period of no growth. By the end of a 16-h culture period, only the acrB transporter gene is still highly overexpressed. Assessment of the activity of genes of the two-component regulon PmrA/B indicates that TZ also activates this regulon. Because activation of pmrA/B also activates acrB, development of high resistance to TZ during a 16-h culture period is in part due to activation of the two-component regulon. PMID- 21982148 TI - Lobectomy in octogenarians with non-small cell lung cancer: ramifications of increasing life expectancy and the benefits of minimally invasive surgery. AB - BACKGROUND: As the population ages, clinicians are increasingly confronted with octogenarians with resectable non-small cell lung cancer (NSCLC). We reviewed the outcomes of octogenarians who underwent lobectomy for NSCLC by video-assisted thoracic surgery (VATS) versus open thoracotomy, to determine if there was a benefit to the VATS approach in this group. METHODS: We conducted a retrospective single-institution review of patients age 80 years or greater who underwent a lobectomy for NSCLC from 1998 to 2009. Outcomes including complication rates, length of stay, disposition, and long-term survival were analyzed. RESULTS: One hundred twenty-one octogenarians underwent lobectomy: 40 VATS and 81 through open thoracotomy. Compared with thoracotomy, VATS patients had fewer complications (35.0% vs 63.0%, p = 0.004), shorter length of stay (5 vs 6 days, p = 0.001), and were less likely to require admission to the intensive care unit (2.5% vs 14.8%, p = 0.038) or rehabilitation after discharge (5% vs 22.5%, p = 0.015). In multivariate analysis, VATS was an independent predictor of reduced complications (odds ratio, 0.35; 95% confidence interval, 0.15 to 0.84; p = 0.019). Survival comparisons demonstrated no significant difference between the two techniques, either in univariate analysis of stage I patients (5-year VATS, 76.0%; thoracotomy, 65.3%; p = 0.111) or multivariate analysis of the entire cohort (adjusted hazard ratio, 0.59; 95% confidence interval, 0.27 to 1.28; p = 0.183). CONCLUSIONS: Octogenarians with NSCLC can undergo resection with low mortality and survival among stage I patients, which is comparable with the general lung cancer population. The VATS approach to resection reduces morbidity in this age demographic, resulting in shorter, less intensive hospitalization, and less frequent need for postoperative rehabilitation. PMID- 21982149 TI - Aortic valve replacement in the elderly: the real life. AB - BACKGROUND: Aortic stenosis is of concern in the elderly. Although aortic valve replacement provides good long-term survival with functional improvement, many elderly patients are still not referred for surgery because of their age. Percutaneous aortic valve implantation offers an alternative to open-heart surgery. Concerns about the management of aortic valve stenosis in the elderly will be reviewed. METHODS: We retrospectively analyzed 1,193 consecutive aortic valve replacements, performed in octogenarians since January 2000. A total of 657 patients (55%) had at least one associated comorbidity (eg, respiratory failure) and 381 (32%) associated coronary lesions. Valve replacement was the only procedure in 883 patients (74%), and was associated with coronary revascularization in 262 cases, or with another cardiac procedure in 48 patients. RESULTS: Overall operative mortality was 6.9% (83 of 1,193 patients); 5.5% for single replacement and 11.5% if associated with coronary artery bypass surgery. Univariate and multivariate analyses identified 11 operative risk factors related to general status, cardiologic condition, and the procedure itself: older age (p<0.015); respiratory failure (p<0.03); aortic regurgitation (p<0.001); emergency surgery (p<0.0029); New York Heart Association class IV (p<0.0007); right heart failure (p<0.03); atrial fibrillation (p<0.04); impaired ejection fraction (p<0.001); coronary disease (p<0.01); redo surgery (p<0.02); associated coronary revascularization (p<0.008). CONCLUSIONS: Today, valve replacement has acceptable low hospital mortality, even in the elderly. Thus, older patients should not be denied surgery due to their advanced age alone. Conventional surgery remains the gold standard treatment for aortic stenosis; the decision should be made on an individual basis. If several risk factors suggest very high risk surgery, then percutaneous valve implantation should be considered instead. PMID- 21982150 TI - Extracorporeal membrane oxygenation for advanced refractory shock in acute and chronic cardiomyopathy. AB - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been used to obtain rapid resuscitation and stabilization in advanced refractory cardiogenic shock (CS), but clear strategies to optimize outcomes and minimize futile support have not been established. METHODS: We retrospectively reviewed our experience with ECMO in patients with advanced refractory CS, after an acute myocardial infarct (AMI) compared with patients receiving ECMO after an acute decompensating chronic cardiomyopathy (CCM). RESULTS: Between January 2003 and February 2009, 33 patients required ECMO support for advanced refractory CS secondary to AMI (AMI CS) and 9 patients were supported by ECMO in the presence of an acutely decompensated CCM (CCM-CS). Survival at 30 days, 1 and 2 years for patients with AMI-CS, was 64%, 48%, and 48% compared with 56%, 11%, and 11% at the same time points for those with CCM-CS (p = 0.05). In the AMI-CS group, 14 of 33 (42%) patients were weaned directly from ECMO after revascularization; 15 of 33 (45%) patients were bridged to ventricular assist device (VAD) support and subsequently either underwent heart transplantation (n = 6), were successfully weaned from VAD (n = 2) or died while on VAD support (n = 7). In the CCM-CS group, 7 patients were bridged to VAD support (77%), with 1 patient surviving after VAD weaning. CONCLUSIONS: Extracorporeal membrane oxygenation in advanced refractory AMI-CS is associated with acceptable outcomes in a well-selected population. The ECMO in patients with an acute decompensation of a chronic CM should be carefully considered, to avoid futile support. PMID- 21982151 TI - Development of national standardized all-hazard disaster core competencies for acute care physicians, nurses, and EMS professionals. AB - The training of medical personnel to provide care for disaster victims is a priority for the physician community, the federal government, and society as a whole. Course development for such training guided by well-accepted standardized core competencies is lacking, however. This project identified a set of core competencies and performance objectives based on the knowledge, skills, and attitudes required by the specific target audience (emergency department nurses, emergency physicians, and out-of-hospital emergency medical services personnel) to ensure they can treat the injuries and illnesses experienced by victims of disasters regardless of cause. The core competencies provide a blueprint for the development or refinement of disaster training courses. This expert consensus project, supported by a grant from the Robert Wood Johnson Foundation, incorporated an all-hazard, comprehensive emergency management approach addressing every type of disaster to minimize the effect on the public's health. An instructional systems design process was used to guide the development of audience-appropriate competencies and performance objectives. Participants, representing multiple academic and provider organizations, used a modified Delphi approach to achieve consensus on recommendations. A framework of 19 content categories (domains), 19 core competencies, and more than 90 performance objectives was developed for acute medical care personnel to address the requirements of effective all-hazards disaster response. Creating disaster curricula and training based on the core competencies and performance objectives identified in this article will ensure that acute medical care personnel are prepared to treat patients and address associated ramifications/consequences during any catastrophic event. PMID- 21982152 TI - Should topical nonsteroidal anti-inflammatory drugs be used to treat acute musculoskeletal conditions? PMID- 21982153 TI - Successful treatment of severe heatstroke with therapeutic hypothermia by a noninvasive external cooling system. AB - Heatstroke is a life-threatening disease; however, no pharmacologic treatment has proven to be effective. In severe cases with multiple organ dysfunction, the mortality remains high and many patients inevitably develop permanent neurologic damage. We report a near-fatal case of exertional heatstroke with multiple organ dysfunction, including generalized convulsions, acute lung injury, and disseminated intravascular coagulation, successfully treated with induced therapeutic hypothermia (33 degrees C [91.4 degrees F]) by a noninvasive external cooling system. After treatment, the patient completely recovered, without any neurologic sequelae during 1 year of follow-up. To our knowledge, this is the first reported case of using therapeutic hypothermia in heatstroke. PMID- 21982154 TI - Two forms of loops generate the chromatin conformation of the immunoglobulin heavy-chain gene locus. AB - The immunoglobulin heavy-chain (IgH) gene locus undergoes radial repositioning within the nucleus and locus contraction in preparation for gene recombination. We demonstrate that IgH locus conformation involves two levels of chromosomal compaction. At the first level, the locus folds into several multilooped domains. One such domain at the 3' end of the locus requires an enhancer, EMU; two other domains at the 5' end are EMU independent. At the second level, these domains are brought into spatial proximity by EMU-dependent interactions with specific sites within the V(H) region. EMU is also required for radial repositioning of IgH alleles, indicating its essential role in large-scale chromosomal movements in developing lymphocytes. Our observations provide a comprehensive view of the conformation of IgH alleles in pro-B cells and the mechanisms by which it is established. PMID- 21982155 TI - Effects of pro-inflammatory cytokines on expression of kynurenine pathway enzymes in human dermal fibroblasts. AB - BACKGROUND: The kynurenine pathway (KP) is the main route of tryptophan degradation in the human body and generates several neuroactive and immunomodulatory metabolites. Altered levels of KP-metabolites have been observed in neuropsychiatric and neurodegenerative disorders as well as in patients with affective disorders. The purpose of the present study was to investigate if skin derived human fibroblasts are useful for studies of expression of enzymes in the KP. METHODS: Fibroblast cultures were established from cutaneous biopsies taken from the arm of consenting volunteers. Such cultures were subsequently treated with interferon (IFN)-gamma 200 U/ml and/or tumor necrosis factor (TNF)-alpha, 100 U/ml for 48 hours in serum-free medium. Levels of transcripts encoding different enzymes were determined by real-time PCR and levels of kynurenic acid (KYNA) were determined by HPLC. RESULTS: At base-line all cultures harbored detectable levels of transcripts encoding KP enzymes, albeit with considerable variation across individuals. Following cytokine treatment, considerable changes in many of the transcripts investigated were observed. For example, increases in the abundance of transcripts encoding indoleamine 2,3-dioxygenase, kynureninase or 3-hydroxyanthranilic acid oxygenase and decreases in the levels of transcripts encoding tryptophan 2,3-dioxygenase, kynurenine aminotransferases or quinolinic acid phosphoribosyltransferase were observed following IFN-gamma and TNF-alpha treatment. Finally, the fibroblast cultures released detectable levels of KYNA in the cell culture medium at base-line conditions, which were increased after IFN gamma, but not TNF-alpha, treatments. CONCLUSIONS: All of the investigated genes encoding KP enzymes were expressed in human fibroblasts. Expression of many of these appeared to be regulated in response to cytokine treatment as previously reported for other cell types. Fibroblast cultures, thus, appear to be useful for studies of disease-related abnormalities in the kynurenine pathway of tryptophan degradation. PMID- 21982156 TI - Cardiac sarcoidosis mimicking arrhythmogenic right ventricular dysplasia with high defibrillation threshold requiring subcutaneous shocking coil implantation. AB - Cardiac involvement in patients with sarcoidosis has been reported in up to 25 39% of patients and is responsible for up to 85% of deaths attributed to the disease, often due to sudden cardiac death. An established diagnosis of cardiac sarcoidosis (CS) portends an ominous prognosis, with an estimated five year survival of 44%. We report a case that was initially diagnosed as arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), but extra-cardiac biopsies later on were consistent with sarcoidosis and a final diagnosis of CS was made. The patient received an implantable cardioverter defibrillator (ICD) with a subcutaneous lead array implant for high defibrillation threshold (DFT). Exclusive right ventricular (RV) involvement is atypical for CS. The predominant RV involvement based on echocardiogram, cardiac magnetic resonance imaging (MRI) and right precordial electrocardiogram changes can lead to misdiagnosis as ARVD/C based on the modified task force criteria. Cardiac sarcoidosis is an under diagnosed disease and the delay in its diagnosis and appropriate therapy can lead to a fatal outcome. High defibrillation thresholds have not been previously reported in patients with CS, but given the natural progression of the disease and the limitations in current pharmacotherapy, implanters who diagnose and treat such patients must be prepared to deal with this issue. PMID- 21982158 TI - Synthesis, characterization and electrochemical behavior of some Ni(II), Cu(II), Co(II) and Cd(II) complexes of ONS type tridentate Schiff base ligand. AB - Tridentate Schiff base (H(2)L) ligand was synthesized via condensation of o hydroxybenzaldehyde and 2-aminothiophenol. The metal complexes were prepared from reaction of the ligand with corresponding metal salts presence of substituted pyridine in two different solvents (MeOH or MeCN). The ligand and metal complexes were then characterized by using FTIR, TGA, (1)H NMR and (13)C NMR spectroscopies. The FTIR spectra showed that H(2)L was coordinated to the metal ions in tridentate manner with ONS donor sites of the azomethine N, deprotonated phenolic-OH and phenolic-SH. Furthermore, substituted pyridine was coordinated to the central metal atoms. The thermal behavior of the complexes was investigated by using TGA method and dissociations indicated that substituted pyridine and ligand were leaved from coordination. This coordination of the metal complexes was correlated by (1)H NMR and (13)C NMR. Finally, electrochemical behavior of the ligand and a Ni(II) complex were investigated. PMID- 21982157 TI - The evidence for Shiatsu: a systematic review of Shiatsu and acupressure. AB - BACKGROUND: Shiatsu, similar to acupressure, uses finger pressure, manipulations and stretches, along Traditional Chinese Medicine meridians. Shiatsu is popular in Europe, but lacks reviews on its evidence-base. METHODS: Acupressure and Shiatsu clinical trials were identified using the MeSH term 'acupressure' in: EBM reviews; AMED; BNI; CINAHL; EMBASE; MEDLINE; PsycARTICLES; Science Direct; Blackwell Synergy; Ingenta Select; Wiley Interscience; Index to Theses and ZETOC. References of articles were checked. Inclusion criteria were Shiatsu or acupressure administered manually/bodily, published after January 1990. Two reviewers performed independent study selection and evaluation of study design and reporting, using standardised checklists (CONSORT, TREND, CASP and STRICTA). RESULTS: Searches identified 1714 publications. Final inclusions were 9 Shiatsu and 71 acupressure studies. A quarter were graded A (highest quality). Shiatsu studies comprised 1 RCT, three controlled non-randomised, one within-subjects, one observational and 3 uncontrolled studies investigating mental and physical health issues. Evidence was of insufficient quantity and quality. Acupressure studies included 2 meta-analyses, 6 systematic reviews and 39 RCTs. Strongest evidence was for pain (particularly dysmenorrhoea, lower back and labour), post operative nausea and vomiting. Additionally quality evidence found improvements in sleep in institutionalised elderly. Variable/poor quality evidence existed for renal disease symptoms, dementia, stress, anxiety and respiratory conditions. Appraisal tools may be inappropriate for some study designs. Potential biases included focus on UK/USA databases, limited grey literature, and exclusion of qualitative and pre-1989 studies. CONCLUSIONS: Evidence is improving in quantity, quality and reporting, but more research is needed, particularly for Shiatsu, where evidence is poor. Acupressure may be beneficial for pain, nausea and vomiting and sleep. PMID- 21982159 TI - Transmasseteric anterior parotid approach for condylar fractures: experience of 129 cases. AB - We have evaluated the transmasseteric anterior parotid (TMAP) approach in the treatment of 163 condylar fractures in 129 patients. Ninety-five patients presented with unilateral, and 34 with bilateral, fractures. The inclusion criteria were patient's choice for open reduction and internal fixation, displaced unilateral condylar fractures with occlusal derangement, and displaced bilateral condylar fractures with anterior open bite. Mean (SD) maximum interincisal opening after 3 months was 44(5)mm. There were no differences in lateral movements during the reviews 6 weeks and 3 months postoperatively. Protrusive movement at the end of 3 months was 7(2)mm. All patients achieved functional occlusion identical to the pretraumatic occlusion and good reduction of the condyles. No patient developed temporary or permanent facial palsy, sialocele, salivary fistula, or Frey syndrome. The mean (SD) operating time was 46(11)min. The TMAP approach avoids the complications of incision of the parotid gland, minimises the risk of facial nerve palsy, and offers excellent access to the fractured condyle. PMID- 21982160 TI - Alzheimer-specific variants in the 3'UTR of Amyloid precursor protein affect microRNA function. AB - BACKGROUND: APP expression misregulation can cause genetic Alzheimer's disease (AD). Recent evidences support the hypothesis that polymorphisms located in microRNA (miRNA) target sites could influence the risk of developing neurodegenerative disorders such as Parkinson's disease (PD) and frontotemporal dementia. Recently, a number of single nucleotide polymorphisms (SNPs) located in the 3'UTR of APP have been found in AD patients with family history of dementia. Because miRNAs have previously been implicated in APP expression regulation, we set out to determine whether these polymorphisms could affect miRNA function and therefore APP levels. RESULTS: Bioinformatics analysis identified twelve putative miRNA bindings sites located in or near the APP 3'UTR variants T117C, A454G and A833C. Among those candidates, seven miRNAs, including miR-20a, miR-17, miR-147, miR-655, miR-323-3p, miR-644, and miR-153 could regulate APP expression in vitro and under physiological conditions in cells. Using luciferase-based assays, we could show that the T117C variant inhibited miR-147 binding, whereas the A454G variant increased miR-20a binding, consequently having opposite effects on APP expression. CONCLUSIONS: Taken together, our results provide proof-of-principle that APP 3'UTR polymorphisms could affect AD risk through modulation of APP expression regulation, and set the stage for further association studies in genetic and sporadic AD. PMID- 21982161 TI - The validation of a new measure quantifying the social quality of life of ethnically diverse older women: two cross-sectional studies. AB - BACKGROUND: To our knowledge, the available psychometric literature does not include an instrument for the quantification of social quality of life among older women from diverse ethnic backgrounds. To address the need for a tool of this kind, we conducted two studies to assess the initial reliability and validity of a new instrument. The latter was created specifically to quantify the contribution of a) social networks and resources (e.g., family, friends, and community) as well as b) one's perceived power and respect within family and community to subjective well-being in non-clinical, ethnically diverse populations of older women. METHODS: In Study 1, we recruited a cross-sectional sample of primarily non-European-American older women (N = 220) at a variety of community locations. Participants were administered the following: a short screener for dementia; a demographic list; an initial pool of 50 items from which the final items of the new Older Women's Social Quality of Life Inventory (OWSQLI) were to be chosen (based on a statistical criterion to apply to the factor analysis findings); the Single Item Measure of Social Support (SIMSS); and the Medical Outcome Study 36-item Short-Form Health Survey (MOS SF-36). Study 2 was conducted on a second independent sample of ethnically diverse older women. The same recruitment strategies, procedures, and instruments as those of Study 1 were utilized in Study 2, whose sample was comprised of 241 older women with mostly non-European-American ethnic status. RESULTS: In Study 1, exploratory factor analysis of the OWSQLI obtained robust findings: the total variance explained by one single factor with the final selection of 22 items was over 44%. The OWSQLI demonstrated strong internal consistency (alpha = .92, p < .001), adequate criterion validity with the SIMSS (r = .33; p < .01), and (as expected) moderate concurrent validity with the MOS SF-36 for both physical (r = .21; p < .01) and mental (r = .26; p < .01) quality of life. In order to confirm the validity of the 22-item OWSQLI scale that emerged from Study 1 analyses, we replicated those analyses in Study 2, although using confirmatory factor analysis. The total variance accounted for by one factor was about 42%, again quite high and indicative of a strong single-factor solution. Study 2 data analyses yielded the same strong reliability findings (i.e., alpha = .92, p < .001). The 22-item OWSQLI was correlated with the SIMSS (r = .27, p < .001) in the expected direction. Finally, correlations with the MOS SF- 36 demonstrated moderate concurrent validity for physical (r = .14; p < .01) and mental (r = .18; p < .01) quality of life, as expected. CONCLUSIONS: The findings of these two studies highlight the potential for our new tool to provide a valid measure of older women's social quality of life, yet they require duplication in longitudinal research. Interested clinicians should consider using the OWSQLI in their assessment battery to identify older women's areas of lower versus higher social quality of life, and should establish the maximization of patients' social quality of life as an important therapeutic goal, as this variable is significantly related to both physical and mental health. PMID- 21982162 TI - Spectral power differences in the brain activity of growth-restricted and normal fetuses. AB - Using non-invasive fetal magnetoencephalography (fMEG), we investigated spontaneous brain activity in 28 fetuses diagnosed with intrauterine growth restriction (IUGR) and compared the results to 47 normal-growth fetuses. The fetal gestational age ranged from 28 to 39 weeks with post-natal recordings obtained on 17 of the IUGR fetuses. Power spectrum was computed and was divided into four frequency bands. A significant difference in the relative spectral power in delta, theta and beta bands (P<0.01) was observed only in the 28-32 week gestation age group with alpha band showing a similar trend (P=0.054). This observation suggests that growth restriction may have a more pronounced effect on the fetal brain in early gestation. Larger population studies could reveal the potential value of fMEG as an additional surveillance tool for growth-restricted fetuses. PMID- 21982163 TI - Longitudinal brain imaging of five malignant glioma patients treated with bevacizumab using susceptibility-weighted magnetic resonance imaging at 7 T. AB - Malignant glioma is a rare tumor type characterized by prominent vascular proliferation. Antiangiogenic therapy with the monoclonal antibody bevacizumab is considered as a promising therapeutic strategy, although the effect on tumor vascularization is unclear. High-field susceptibility-weighted imaging (SWI) visualizes the microvasculature and may contribute to the investigation of antiangiogenic therapy responses in gliomas. We prospectively studied five adult malignant glioma patients treated with bevacizumab-containing regimens. In each patient, we performed three 7-T SWI and T1-weighted imaging investigations (baseline and 2 and 4 weeks after the start of bevacizumab treatment). In addition, we imaged a postmortem brain of a patient with glioblastoma using 7-T SWI and performed detailed histopathological analysis. We observed almost total resolution of brain edema in three of five patients after initiation of bevacizumab therapy. In one case with rapid increase of the lesion size despite bevacizumab therapy, SWI showed progressive increase of irregular hypointense structures, most likely corresponding to increasing amounts of pathological microvasculature. In one case with progressive neurological decline, 7-T images showed multiple intratumoral microhemorrhages after the first bevacizumab application. Correlation of postmortem neuroimaging with histopathology confirmed that SWI-positive structures correspond to tumor vasculature. The experience from our case series indicates that longitudinal 7-T SWI seems to be an appropriate method for investigation of changes in brain tumor vascularization over time under antiangiogenic therapy. PMID- 21982164 TI - Aberrant default mode network in subjects with amnestic mild cognitive impairment using resting-state functional MRI. AB - Amnestic mild cognitive impairment (aMCI) is a syndrome associated with faster memory decline than normal aging and frequently represents the prodromal phase of Alzheimer's disease. When a person is not actively engaged in a goal-directed task, spontaneous functional magnetic resonance imaging (fMRI) signals can reveal functionally connected brain networks, including the so-called default mode network (DMN). To date, only a few studies have investigated DMN functions in aMCI populations. In this study, group-independent component analysis was conducted for resting-state fMRI data, with slices acquired perpendicular to the long axis of the hippocampus, from eight subjects with aMCI and eight normal control subjects. Subjects with aMCI showed an increased DMN activity in middle cingulate cortex, medial prefrontal cortex and left inferior parietal cortex compared to the normal control group. Decreased DMN activity for the aMCI group compared to the normal control group was noted in lateral prefrontal cortex, left medial temporal lobe (MTL), left medial temporal gyrus, posterior cingulate cortex/retrosplenial cortex/precuneus and right angular gyrus. Although MTL volume difference between the two groups was not statistically significant, a decreased activity in left MTL was observed for the aMCI group. Positive correlations between the DMN activity and memory scores were noted for left lateral prefrontal cortex, left medial temporal gyrus and right angular gyrus. These findings support the premise that alterations of the DMN occur in aMCI and may indicate deficiencies in functional, intrinsic brain architecture that correlate with memory function, even before significant MTL atrophy is detectable by structural MRI. PMID- 21982165 TI - Fine-scale functional connectivity in somatosensory cortex revealed by high resolution fMRI. AB - High-resolution functional magnetic resonance imaging (fMRI) at high field (9.4 T) has been used to measure functional connectivity between subregions within the primary somatosensory (SI) cortex of the squirrel monkey brain. The hand-face region within the SI cortex of the squirrel monkey has been previously well mapped with functional imaging and electrophysiological and anatomical methods, and the orderly topographic map of the hand region is characterized by a lateral to medial representation of individual digits in four subregions of areas 3a, 3b, 1 and 2. With submillimeter resolution, we are able to detect not only the separate islands of activation corresponding to vibrotactile stimulations of single digits but also, in subsequent acquisitions, the degree of correlation between voxels within the SI cortex in the resting state. The results suggest that connectivity patterns are very similar to stimulus-driven distributions of activity and that connectivity varies on the scale of millimeters within the same primary region. Connectivity strength is not a reflection of global larger-scale changes in blood flow and is not directly dependent on distance between regions. Preliminary electrophysiological recordings agree well with the fMRI data. In human studies at 7 T, high-resolution fMRI may also be used to identify the same subregions and assess responses to sensory as well as painful stimuli, and to measure connectivity dynamically before and after such stimulations. PMID- 21982166 TI - Dexamethasone: not only an effective antiemetic. PMID- 21982167 TI - The effect of anesthetic techniques on neutrophil-to-lymphocyte ratio after laparoscopy-assisted vaginal hysterectomy. AB - BACKGROUND: Surgical stress can induce postoperative systemic leukocytic alterations, including leukocytosis, neutrophilia, or lymphopenia. The present study investigated whether the anesthetic technique could affect the leukocytic alterations, including neutrophil-to-lymphocyte (N/L) ratio, after gynecologic laparoscopy. METHODS: Forty patients scheduled for laparoscopy-assisted vaginal hysterectomy were randomly assigned into two groups: PR group, which received total intravenous anesthesia with propofol and remifentanil, and S group, which received inhalational anesthesia with sevoflurane. Differential counts of leukocytes with N/L ratio of peripheral blood were obtained just before induction (T1), at the end of surgery (T2), 2 hours after surgery (T3), and 24 hours (T4) after surgery. RESULTS: Significant increase in total leukocytic count, neutrophil count, and N/L ratio, and decrease in lymphocytic count were observed at all time points after surgery in both groups. N/L ratio was significantly lower in group PR compared with group S at T3. The increase of N/L ratio in contrast to the value at T1 was significantly lower at T2 and T3 in group PR compared with that of group S. CONCLUSION: Total intravenous anesthesia with propofol and remifentanil resulted in transient but salient leukocytic alterations in the peripheral blood in terms of N/L ratio compared with inhalational anesthesia with sevoflurane in laparoscopy-assisted vaginal hysterectomy. PMID- 21982168 TI - The use of the GlideScope(r) for tracheal intubation in patients with halo vest. AB - OBJECTIVE: GlideScope(r) provides better laryngoscopic view and is advantageous in tracheal intubation in ankylosing spondylitis patients with difficult airway. METHODS: This study was performed to investigate the use of the GlideScope(r) for tracheal intubation in 15 patients wearing halo vests scheduled for elective surgery under general anesthesia. Preoperative airway assessments were evaluated to predict the difficulty of tracheal intubation. Before intubation, all patients were given a modified Cormack and Lehane (MCLS) grade and percentage of glottic opening (POGO) score by the intubating anesthesiologist having resorted to direct laryngoscopy (DL) with a Macintosh Size 3 blade depiction. Then intubation with the GlideScope(r) was performed, during which the larynx was inspected and given another MCLS grade and POGO score. RESULTS: Fourteen of the 15 patients had MCLS Grade III or IV by direct Macintosh laryngoscopy and were considered to have a difficult laryngoscopy. Nasal tracheal intubation by the GlideScope(r) was successful on all occasions. The GlideScope(r) improved the MCLS grade and POGO score in all patients who had put on a halo vest as compared with those on DL (p<0.01). The GlideScope(r) also provided a better laryngoscopic view than that by a DL. All of the patients who wore halo vests and presented with suspected difficult airways could be intubated successfully with the GlideScope(r). CONCLUSION: The use of the GlideScope(r) for tracheal intubation could be an alternative option in patients with a difficult airway, whose surgery was circumscribed under general anesthesia with tracheal intubation. PMID- 21982169 TI - The effect on improvement of recovery and pain scores of paravertebral block immediately before breast surgery. AB - OBJECTIVES: Paravertebral block (PVB) has the potential to reduce postoperative pain after breast surgery. The aim of the study was to investigate whether PVB performed immediately before surgery could affect the postoperative morbidities in terms of pain and emesis, and improve the quality of recovery (QoR) in patients after surgery for breast cancer. METHODS: Postoperative data were collected prospectively from two groups of patients undergoing unilateral breast surgery during the study period of 1 month. Forty consecutive patients received either solely general anesthesia (GA group, n=25) or GA plus ultrasound-guided PVB (GA+PVB group, n=15) for the surgery. Pain scores and areal distribution of pain were compared between the two groups 1 hour and 6 hours postoperatively and on the midmorning of postoperative Day 1 (POD1). The QoR scores were compared between the two groups 6 hours postoperatively and on the midmorning of POD1. Incidence of postoperative nausea and vomiting and doses of analgesics and narcotics given were also compared. RESULTS: Pain scores at rest were significantly lower in the GA+PVB group at all designated time points [1 hour (p<0.0001), 6 hours (p<0.0001), and on midmorning of POD1 (p=0.041)]. Pain scores with movements was also significantly lower at all time points in the GA+PVB group (1 hour, p<0.0001; 6 hours, p<0.0001; midmorning of POD1, p=0.0012). Areal distribution of pain at rest and with movement was wider in the GA group 1 hour and 6 hours postoperately but was identical to that of GA+ PVB group on the mid morning of POD1 [1 hour postoperatively at rest (p<0.0001), with movement (p<0.0001); 6 hours postoperatively at rest (p=0.0018), with movement (p=0.0048)]. The QoR scores were significantly higher in the GA+PVB group at 6 hours (p<0.0001) and on midmorning of POD1 (p=0.0079). The incidences of postoperative nausea and vomiting were significantly lower in the GA+PVB group (p=0.0004). Doses of postoperative analgesics and narcotics were significantly less in the GA+PVB group (p<0.0001 and p=0.001, respectively). Time to first request for analgesics was significantly longer in the GA+PVB group (p=0.0002). CONCLUSIONS: PVB given before surgery in combination with GA could provide better postoperative analgesia and better QoR than did GA alone in patients undergoing surgery for unilateral breast cancer. PMID- 21982170 TI - Postoperative agitation in preschool children following emergence from sevoflurane or halothane anesthesia: a randomized study on the forestalling effect of midazolam premedication versus parental presence at induction of anesthesia. AB - OBJECTIVE: The effect of midazolam premedication on forestalling postoperative agitation in children is not yet concluded. The purpose of this study was to compare the effects of midazolam premedication and parental presence during anesthetic induction on the incidence of postoperative agitation in pediatric patients. METHODS: One hundred sixty-seven children between 2 years and 7 years of age, undergoing anesthesia for outpatient surgery, were enrolled and randomly divided into four groups: sevoflurane anesthesia with parental presence without premedication, sevoflurane anesthesia with oral midazolam premedication, halothane anesthesia with parental presence without premeditation, and halothane anesthesia with oral midazolam premedication. The children randomized to the premedication groups took oral midazolam 0.5mg/kg 20-30 minutes before anesthetic induction. For patients in the groups without premedication, one of the parents was present throughout the induction of anesthesia. One recovery room nurse blinded to the group assignment observed the patients and recorded the agitation scores all through their stay in the postanesthesia care unit. RESULTS: Postoperative agitation was significantly less in patients who received halothane anesthesia with oral midazolam premedication (p<0.002). CONCLUSION: Based on our data, the presence of a parent at induction of sevoflurance anesthesia was as effective as midazolam premedication in decreasing the incidence of postoperative agitation. Midazolam premedication, however, decreased postoperative agitation when halothane was used as the anesthetic agent. PMID- 21982171 TI - Dexamethasone prevents postoperative nausea and vomiting: benefit versus risk. AB - Postoperative nausea and vomiting (PONV) is a common annoying experience after surgery. The overall incidence of PONV in adults is 20-30%; the incidence rate in patients of high-risk groups can be as high as 70-80%. Children are not exempted from attacking either; the incidence rate in children above the age of 3 is more than 40%. The incidence slowly drops after puberty, sharing the same rate with adults. Dexamethasone can be effective in preventing PONV in adults and children. Compared with other preventive medications, dexamethasone has equal or even better efficacy in reducing the incidence of PONV and has the advantages of low cost and longer effectiveness as well. Although the action mechanism of dexamethasone is hitherto not fully understood, animal studies have confirmed that the vomiting center in the brain stem plays a central role. A combination of dexamethasone with other antiemetics is more effective than any single drug alone. Additionally, the use of dexamethasone to prevent nausea and vomiting triggered by intravenous or epidural morphine for pain control can also offer a good therapeutic effect. To date, clinically, dexamethasone as a preventative drug against PONV has not caused fatal outcome; therefore, it is generally considered to be an effective and safe antiemetic. Nevertheless, its use in this regard may lead to adverse effects, principally postoperative hyperglycemia and infection. PMID- 21982173 TI - Apparatus and simple method of monitoring neuromuscular function. AB - The use of muscle relaxant is an integral part of anesthetic management in present-day practice. Clinically, the neuromuscular blockade is evaluated by determining the thumb twitching to train-of-four (TOF) ulnar nerve stimulation at elbow.(1-3) There are many ways for the assessment of twitch response, such as the use of electromyography(4,5); force displacement transducer techniques(2,6 9); and most recently, the acceleration transducer-based system of neuromuscular monitoring.(10-15) These equipments are, however, bulky, cumbersome, expensive, or time consuming for operation. Because of these limitations, the routine use of such monitors is impractical. The evaluation of neuromuscular blockade, at the present time, relies on either visual or manual (tactile) thumb twitch responses to the TOF nerve stimulation. Visual or tactile evaluation of neuromuscular blockade is subjective and involves uncertainty, especially in the recovery phase. Furthermore, in certain surgical procedures, such as those on the head and neck, both hands are tucked in the sides of the table and become inaccessible, rendering visual or tactile evaluation of the thumb twitch impossible. In such situation, muscle relaxant is often given in the light of guessing rather than on objective basis. Clearly, there is a need for a simple and practical way of measuring the twitch responses to TOF stimulation during anesthesia. Based on the current method of stimulation of the ulnar nerve over the ulnar groove at the elbow, which elicits a string thumb adduction (because of stimulation of the flexor carpi ulnaris muscle), a simple method that can objectively monitor and record the thumb twitch is developed. The unique features of the method or device are its simplicity and its ability to adapt to any pressure transducer to display the twitch response to TOF simultaneously with electrocardiogram, arterial, or central venous pressure. PMID- 21982172 TI - Influence of morphine on host immunity. AB - Morphine is a widely used drug for analgesia and substance abuse. It has been accepted as a safe medication with great analgesic efficacy. Previous studies have reported that morphine is highly associated with the risk of immunosuppressive effects. Although the observed clinical effects suggest that morphine has the immunomodulatory capabilities, the mechanism of its action is still unclear. Here we review morphine on the bench to improve our understanding of the drug on the host immunity at the bedside. Studies of the effects of morphine on the innate and adaptive immune systems as well as immune responses are also discussed. PMID- 21982174 TI - Spinal cord imaging by transesophageal echocardiography: a new modality of monitoring. AB - A 45-year-old patient with known history of Aortic arch aneurysm presented in the emergency ward with features of rupture of the aneurysm into the left lung with compressive signs in the pulmonary parenchyma. Diagnosis was confirmed by magnetic resonance imaging. The patient underwent repair of thoracic aortic aneurysm with left upper lobectomy under general anesthesia and cardio-pulmonary bypass support. Transesophageal echocardiography (TEE) was used for an intraoperative monitoring. While imaging the thoracic aorta with TEE was underway, we accidentally visualized an image that was confirmed to be the spinal cord. So, in this article we discuss how the spinal cord monitoring can be made possible with TEE. PMID- 21982175 TI - Successful management of contrast medium extravasation injury through stellate ganglion block and intra-arterial nitroglycerin. AB - We describe the successful management of extravasation injury to the left hand by contrast medium with stellate ganglion block and intra-arterial nitroglycerin in a patient which befell during contrast-enhanced imaging. The incidence of contrast-medium extravasation injury is increasing because of the convenience and availability of contrast-enhanced imaging and ease of injection access. Extravasation of contrast medium may results in severe pain, erythema, cyanosis, and edema or even skin necrosis, which is largely related to the ionization, osmolarity, and volume of the contrast medium. The conservative treatment is often adequate in small amount extravasation, but if the extravasation is overwhelming further energetic management is mandatory. A 29-year-old man was brought to our emergency because of diffuse abdominal pain and he was arranged to receive intravenous contrast media enhanced abdominal computed tomography for diagnosis. Ruptured appendicitis with abscess formation was suspected; then the patient underwent emergent appendectomy and drainage of the abscess. However, severe swelling and cyanotic change that radiated from the intravenous catheter insertion site in every direction over the entire dorsum of the left hand were noted after the surgery. Contrast-medium extravasation injury was highly contemplated and a left stellate ganglion block was performed immediately for relief of symptoms. The consulting surgeon ruled out compartment syndrome, but advised emergent left upper limb arteriography, which revealed signs of vasospasm with high intravascular pressure of the left distal ulnar and radial arteries; thus nitroglycerin was injected into left distal ulnar and radial arteries for relief of vasospasm. The clinical symptoms were improved after the above managements and the patient was discharged 7 days later without any sequela. PMID- 21982176 TI - Modified glove fingers as an aid for safely navigating endotracheal tube through the nasal cavity and nasopharynx in difficult nasotracheal intubation. AB - A young female patient scheduled for orthognathic surgery under general anesthesia encountered obstacles during nasotracheal intubation in which the cuff of the nasal endotracheal tube was linearly lacerated and the tube tip impacted against the retropharyngeal wall. Repeated episodes of the event happened rendering the intubation unsuccessful. A technique using modified glove fingers was applied, which successfully protected the cuff from shearing by the sharp nasal crista and redirected the tube tip away from the retropharyngeal wall. It is a simple and applicable technique during nasotracheal intubation to prevent cuff damage and potential retropharyngeal dissection. PMID- 21982177 TI - Schizophrenia: a five-year follow-up of patient outcome following psycho education for caregivers. AB - INTRODUCTION: There is evidence that psycho-education courses for caregivers of individuals with schizophrenia improve the short-term outcome of the condition. However, most of the outcome studies are limited to two-year follow-up. MATERIALS AND METHODS: This study is a five-year retrospective case-control follow-up of an original cohort of 63 patients and their 101 caregivers who completed a six-week Caregiver Psycho-education Programme (CPP) for schizophrenia and psychosis between 2002 and 2005, and 60 controls, matched for age, gender and severity of their psychotic illness. RESULTS: Patients whose caregivers learned more from the six-week psycho-education course had a significantly longer time to relapse (P = 0.04) and a significantly shorter length of stay during their first relapse (P < 0.05). Patients whose caregivers attended the six-week psycho-education course (regardless of how much the caregivers learned) had a significantly better outcome than controls. This included a significantly smaller number of relapses (P < 0.01), longer time to relapse (P < 0.01), shorter length of stay during their first relapse (P < 0.01) and smaller number of bed days over five years (P < 0.01). The odds ratio of controls relapsing, although insignificant at one year, was 4.13 (1.85-9.21) at five years. Outcome was not affected by either the numbers of caregivers attending for each patient, or caregiver gender. DISCUSSION AND CONCLUSIONS: This study, which is among the first to examine outcome over five years, supports the efficacy of psycho-education for caregivers in improving outcome for patients. Caregivers should be encouraged to take up psycho-education where it is available. PMID- 21982178 TI - Induction of apoptosis and inhibition of cell growth by tbx5 knockdown contribute to dysmorphogenesis in Zebrafish embryos. AB - BACKGROUND: The tbx5 mutation in human causes Holt-Oram syndrome, an autosomal dominant condition characterized by a familial history of congenital heart defects and preaxial radial upper-limb defects. We report aberrant apoptosis and dormant cell growth over head, heart, trunk, fin, and tail of zebrafish embryos with tbx5 deficiency correspond to the dysmorphogenesis of tbx5 morphants. METHODS: Wild-type zebrafish embryos at the 1-cell stage were injected with 4.3 nl of 19.4 ng of tbx5 morpholino or mismatch-tbx5-MO respectively in tbx5 morphants and mismatched control group. Semi-quantitative RT-PCR was used to for expression analysis of apoptosis and cell cycle-related genes. TUNEL and immunohistochemical assay showed the apoptosis spots within the local tissues. Ultra-structure of cardiac myocardium was examined by transmission electron microscope. RESULTS: Apoptosis-related genes (bad, bax, and bcl2), and cell cycle related genes (cdk2, pcna, p27, and p57) showed remarkable increases in transcriptional level by RT-PCR. Using a TUNEL and immnuohistochemical assay, apoptosis was observed in the organs including the head, heart, pectoral fins, trunk, and tail of tbx5 knockdown embryos. Under transmission electron microscopic examination, mitochondria in cardiomyocytes became swollen and the myocardium was largely disorganized with a disarrayed appearance, compatible with reduced enhancement of myosin in the cardiac wall. The ATP level was reduced, and the ADP/ATP ratio as an apoptotic index significantly increased in the tbx5 deficient embryos. CONCLUSION: Our study highlighted that tbx5 deficiency evoked apoptosis, distributed on multiple organs corresponding to dysmorphogenesis with the shortage of promising maturation, in tbx5 knockdown zebrafish embryos. We hypothesized that mesenchymal cell apoptosis associated with altered TBX5 level may subsequently interfered with organogenesis and contributed to dysmorphogenesis in tbx5 deficiency zebrafish embryos. PMID- 21982180 TI - [Congenital cholesteatoma in children]. AB - OBJECTIVES: To report on two cases of congenital cholesteatoma in patients aged 1 month. To review the clinical and radiological features of congenital cholesteatoma and to clarify the contribution of the CT scan in the diagnosis and the preoperative workup. PATIENTS AND METHODS: The authors report two observations of congenital cholesteatoma. These children were investigated using high-resolution CT. The treatment was surgical in both cases. RESULTS: The children were 1 month old, presenting with facial paralysis. In the otoscopic exam, the tympanic membrane was normal in both cases, with a whitish retrotympanic soft mass. The diagnosis of congenital cholesteatoma was made based on the CT data. CONCLUSION: Congenital cholesteatoma is rare. Otoscopic examination must be undertaken during the physical exam of a child at a young age to establish an early diagnosis. CT scan allows positive diagnosis and a precise preoperative workup. PMID- 21982179 TI - Feasibility of written instructions in airway management training of laryngeal tube. AB - BACKGROUND: Airway management is of essential importance in emergency care. Training and skill retention of endotracheal intubation (ETI) - the technique considered as the "gold standard" -, poses a problem especially among care providers experiencing a low frequency of airway management situations. Therefore, alternative airway devices such as the laryngeal tube (LT) with potentially steeper learning curves have been developed and studied. Our aim was to evaluate in a manikin model the use of LT after no other training than written instructions only. METHODS: To evaluate the amount of training required to use the LT in a scenario of airway compromise, we assessed the feasibility of providing written instructions and pictures showing its use to 67 out- and in hospital emergency care providers attending an Emergency Care conference. The majority of the participants were either nurses or firemen with a median of 5 years' history of work in emergency care. RESULTS: In this study 55% of all participants inserted the LT on the first attempt without additional instructions. An additional 42% required verbal instructions before successful insertion. Overall, 97% of the participants successfully inserted the LT with two attempts.In logistic regression analysis, no relationship was detected between background variables (basic education, experience of emergency work, frequency of bag-valve-mask ventilation (BVM) and frequency of ETI) and successful insertion of the LT in less than 30 seconds, ability to maintain normoventilation (7 l/min) and need for further instructions during the test. CONCLUSIONS: We found that in this pilot study majority of emergency care providers could insert LT with one or two attempts with written instructions, pictures and verbal instruction. This may provide an option to simplify the training of airway management with LT. PMID- 21982181 TI - [The problem of the venous thromboembolic disease in Mexico]. AB - It is necessary to spread the knowledge about the disease, however, venous thromboembolic guidelines published in this issue give little attention to prevention, minimize the evaluation of the risk factors, do not evaluate its impact on the non-surgical patient, and do not emphasize the benefits of non pharmacological and extended thromboprophylaxis. Guidelines for clinical practice of the Instituto Mexicano del Seguro Social must suggest the way to attend patients at the lowest cost with quality. Because prevention is the best tool to fight VTD, these guidelines do not totally accomplish their institutional objectives. PMID- 21982182 TI - [Comparative study of direct cost between open and laparoscopic cholecystectomy]. AB - OBJECTIVE: to compare the direct cost of open cholecystectomy (OCL) with laparoscopic cholecystectomy (LCL), using a microcosting approach. METHODS: in patients who underwent cholecystectomy (C) in the Hospital General de Mexico, we collected patient age and sex, time in the operative room (OR), anesthesia and surgical procedure; health personal (HP) involved; materials (M) and medications consumed; medical instruments (MI) and medical equipment (ME) used. RESULTS: there were 355 patients operated by C, were 248 included, 94 with CAB and 74 with CLP. CAB surgical time was longer than CLP (102 versus 82, p<0.00.1); CLP had a higher use of materials intraoperative ($5 329 versus $1 403, p<0.001). There are no differences in: cost for HP, MI and ME. The total direct cost was $7238 (US$615) for CAB and $12 507 (US$1 063) for CLP (p <0.001) at 11.76 Mexican pesos per dollar. CONCLUSIONS: the difference in costs between OCL and LCL is primarily explained by the cost of lab exams which represent 79% of the M cost for CLP. PMID- 21982183 TI - [Carotid angioplasty with stent in patients at high risk: intra-hospital results and long-term monitoring]. AB - BACKGROUND: carotid angioplasty with stent (ACS) represents a less invasive alternative to carotid endarterectomy (CEA) for treatment of carotid occlusive disease. Our objective was to analyze the morbidity and mortality 30 days and 6 months after ACS. METHODS: we included 206 patients (231 lesions) with a mean age of 67.46 +/- 8.37 years, 40 patients (19.4 %) > 75 years, 66 % were symptomatic, 169 patients (82 %) with history of ischemic heart disease; in 213 lesions (92.2 %) cerebral protection filters were used; clopidogrel 300 mg; aspirin 325, heparin IV 70 UI/kg, temporary pacemaker prophylaxis in ostial lesions of the internal carotid artery were applied. RESULTS: complications were four procedure related deaths (1.9 %), five major neurological events (2.16 %) and three minor events (1.3 %); in 104 patients (50.4 % ) a successful coronary angioplasty also was done; the mean follow-up was 26.5 +/- 23.2 days; five patients had re stenosis on Doppler but the angiography documented it only in three patients (1.3 % ), Two of them undergoing uncomplicated PTA. Five patients died over the follow up, two presented myocardial infarction (MI), two more with a infectious condition and one had not identified the cause. CONCLUSIONS: the ACS is an alternative to surgery in patients with symptomatic carotid disease. PMID- 21982184 TI - Trypanosoma cruzi antibodies in blood donors in Yucatan state, Mexico. AB - BACKGROUND: Blood transfusion is the second most frequent way of Trypanosoma cruzi (T. cruzi) transmission in Latin American countries. Few data exists on the geographic distribution and prevalence of T. cruzi seropositive blood donors in Mexico. The objective was to document T. cruzi antibody distribution, and identify the regions with the highest prevalence of seropositive blood donors. METHODS: the analyzed data was collected over a six-year period during blood donations made at the Central Blood Bank and at the transfusion services and donation modules of the Instituto Mexicano del Seguro Social (IMSS) located in the Yucatan state. RESULTS: Trypanosoma cruzi antibody reactivity was determined in 86343 blood donors. Overall seroprevalence was 0.70 % (607/86 343). Since 2002 to 2004, the majority (58 %) of seropositive donors were rural residents, but since 2005 to 2007 the majority (56.6 %) were urban residents. The two highest seroprevalences by region were in the Metropolitan area (0.42 %) and in rural south Yucatan (0.09 %). Most seropositive donors resided in the municipality of Merida (60.3 %). CONCLUSIONS: seroprevalence distribution was heterogeneous during the study period but urban transmission has apparently surpassed rural transmission in recent years. PMID- 21982185 TI - [Evaluation of a rapid immunological test for tuberculosis diagnosis]. AB - OBJECTIVE: To demonstrate whether patients undergoing capsulotomy Nd: YAG laser developed intraocular hypertension after the procedure. METHODS: Prospective, pre experimental before and after 2 measurements with post-test in patients with posterior capsular opacity from the Ophthalmology Service. Measurements of intraocular pressure (IP) before capsulotomy Nd: YAG laser, and three hours and one week later. RESULTS: We studied 47 patients, 29.8 % were men and 70.2 % women. We compared between visual acuity before and one week later (Wilcoxon test p = 0.00). IP after three hours and one week later, comparisons with Friedman test were done (p =0. 002). We compared the IP prior and one week later (Wilcoxon test, with p =0.815). IP before and three hours later were obtained (p = 0.001) and IP three hours and one week later (p = 0.004). CONCLUSIONS: We found an increase in IP in the first hours after the capsulotomy Nd: YAG laser, which decrease gradually until reaching the values presented before the procedure, in not more than a week period. It is a quick and safe procedure to treat posterior capsular opacity. PMID- 21982186 TI - [Smart search as the only way to filter a lot of information]. PMID- 21982187 TI - [Diet and cholelitiasis. Are the diets without cholecystoquinetics justified?]. PMID- 21982188 TI - [The venous thromboembolic disease]. AB - Venous thromboembolic disease (VTD) is a frequent medical problem. The VTD includes deep vein thrombosis (DVT), the posthrombotic syndrome (PTS) and pulmonary embolism (PE). The generation of a thrombus in the venous system, is caused by several abnormalities that induce the loss of the most important characteristic of the blood, the liquid state. DVT is due to the formation of a thrombus. Main causes for thrombus formation are thrombophilias which may be classified as primary and secondary. All thrombophilias may affect the homeostasis favoring a hypercoagulable state. In the XIX Century, Virchow classified all the causes of hypercoagulable states as follows: due to stasis of the venous blood flow, due to damage of the endothelium an a hypercoagulable clinical condition. Several risk factors for VTD has been described, during the hospitalization to both, medical and surgical conditions. Among the last, orthopedic and vascular surgery of the legs. Although nearly 50 % of DVTs are asymptomatic and 3 % of the patients with VTD develop PE and 30 % of them die. Thromboprophylaxis is the main strategy to prevent and to diminish the incidence of DVT and its complications. Thromboprophylaxis is useful to improve the quality of life of the patients at risk and it is an effective economical strategy for health care institutions. PMID- 21982189 TI - [The new oral anticoagulants in surgery]. AB - We can estimated the probability of developing thromboembolic disease and consequently prescribed antithrombotic measures to patients undergoing surgery. The anticoagulants carry the risk of abnormal bleeding, which can sometimes be fatal. Recently, this concept changed with the development of new drugs that retain their antithrombotic activity but decrease their anticoagulant effect; other advantages are: route of administration, predictable bioavailability (generally do not require monitoring), and little interaction with food and other drugs. The most representative are direct factor Xa inhibitors like apixaban and rivaroxaban as well as factor IIa inhibitors, such as dabigatran. They had been evaluated in patients undergoing hip or knee surgery in comparison with low molecular weight heparins; in general they had better results in efficacy and similar results in safety. Trials are now underway to evaluate their use in other surgical and nonsurgical environments. Today, the surgical patient is older and has comorbidities, such as atrial fibrillation, prosthetic valves, diabetes mellitus, hypertension, and other chronic diseases. These patients need be protected from thrombosis with low bleeding risk. New antithrombotic drugs offer a margin of safety and maintain efficacy; therefore, they constitute an advantage over classical anticoagulant drugs. We highlight concepts related with the need for thromboprophylaxis and the new antithrombotic medication in a surgical context. PMID- 21982190 TI - [Clinical research IV. Relevancy of the statistical test chosen]. AB - When we look at the difference between two therapies or the association of a risk factor or prognostic indicator with its outcome, we need to evaluate the accuracy of the result. This assessment is based on a judgment that uses information about the study design and statistical management of the information. This paper specifically mentions the relevance of the statistical test selected. Statistical tests are chosen mainly from two characteristics: the objective of the study and type of variables. The objective can be divided into three test groups: a) those in which you want to show differences between groups or inside a group before and after a maneuver, b) those that seek to show the relationship (correlation) between variables, and c) those that aim to predict an outcome. The types of variables are divided in two: quantitative (continuous and discontinuous) and qualitative (ordinal and dichotomous). For example, if we seek to demonstrate differences in age (quantitative variable) among patients with systemic lupus erythematosus (SLE) with and without neurological disease (two groups), the appropriate test is the "Student t test for independent samples." But if the comparison is about the frequency of females (binomial variable), then the appropriate statistical test is the chi(2). PMID- 21982191 TI - [Experience with a "Telederma Program" in a family medicine unit]. AB - Telemedicine represents the practice of medicine over distance; it goes from establishing a diagnosis to the implementation of a therapeutic plan and patient follow up. In a primary care unit, a teledermatology program was implemented in September 2007, with a total of 1874 patients attended, achieving a reduction of the waiting time for a dermatologic attention from six months to seven days. Special interest deserves the immediate recognition and treatment of those patients whose diagnosis is correlated with a poor prognosis. The objective is to share the experience acquired during the three years of the program, called Telederma, as an alternative of specialized dermatological care. PMID- 21982192 TI - [Alcohol consumption in women and its relation with the psychopathology in primary health care]. AB - OBJECTIVE: To determine the frequency of alcohol consumption in women and their relation with symptom of psychopathology. METHODS: Cross-sectional, correlation descriptive study, in a sample of 374 women between 18 to 65 years that were attended at an unit of family medicine. Sociodemographic variables (age, marital status, occupation, schooling, socioeconomic level) were obtained; Test AUDIT (Alcoholism Use Disorders Identification Test) and Symptom Check List 90 (SCL-90) items to measure psychopathology were also applied. It was realized univariate and bivariate analysis. RESULTS: The average age was 34.68 +/- 11.84 years, 11.2 % with elevated risk of alcohol consumption; 47.6 % with positive alcohol consumption; 72.4 % with a partner; 85.6 % secondary school and more; 48.7 % occupation housewife. Low and very low socioeconomic level in 21.9 %. The dimensions with majors values were somatitation (0.563), depression (0.526), obsession-compulsions (0.525) and phobic anxiety (0.511). There is an important increase in averages SCL-90 for the patients with elevated risk of alcohol consumption, these differences were significative (p = 0.00005). CONCLUSIONS: The average of nine dimensions of SCL-90 was greater for patients with elevated risk of alcohol consumption. PMID- 21982193 TI - [Patient and physicians' factors associated to no metabolic control in type 2 diabetics]. AB - BACKGROUND: the understanding of the factors associated with a lack of metabolic control (NMC) in diabetic patients is essential. The aim was to determine the factors associated to NMC in diabetic patients. METHODS: comparative cross sectional survey with a non probabilistic sample at a primary care unit was done. We investigated the factors associated to NMC through a structured survey exploring social, demographics and the attachment to diet, exercise and pharmacological treatment with emphasis on the self-conception about the disease and its treatment. The knowledge about the guidelines of clinical practice on diabetes was also explored on physicians. RESULTS: we included 266 patients and 32 physicians. The metabolic control was good in 1.1 %; acceptable 6.7 % and NMC 92.1 % (n = 245). The age, index of corporal mass (ICM) and psychological stress (scale of Holmes) were related significantly to NMC. The 87.2 % of patients recognized not be attached to the dietetic treatment and 50 % referred to no carry out exercise. The labor variables or the physician's knowledge about Clinical Guidelines are not related to NMC. CONCLUSIONS: the most of the type 2 diabetic patients are NMC and the ICM were the variable most frequently associated. PMID- 21982194 TI - [Necrotizing fasciitis and group A streptococcal toxic shock syndrome in two patients without risk factors]. AB - Necrotizing fasciitis associated to group A streptococcus (S. pyogenes) infection is a deep-seated infection of the subcutaneous tissue that results in progressive destruction of fascia and fat, with a high mortality rate due to a rapid progression of the illness to shock and multiple organ dysfunction. The challenge is to perform a prompt diagnosis because it is often confused with a minor soft tissue infection. This infection should be aggressively treated with systemic antimicrobials, surgical debridement, and critical care. We present two cases of necrotizing fasciitis associated to infection with Streptococcus pyogenes patients developed myonecrosis and toxic shock syndrome within the following 24 hours after admission. In addition, we reviewed the pathogenic mechanism, diagnosis and treatment of this syndrome and discuss published treatment recommendations. PMID- 21982195 TI - [Septic shock by Vibrio vulnificus at the coast Gulf of Mexico]. AB - Vibrio vulnificus is a Gram-negative bacterium which is found in marine environments and where there is a partly enclosed coastal body of water with one or more rivers or streams flowing into it, and with a free connection to the open sea. The infection by these bacteria can cause primary septicemia by two mechanisms: upon consuming crustaceans, mollusks and some fish (filtering shellfish) raw or barely cooked or by an open injury in contact with seawater. The patients with infections of the primary injury by Vibrio vulnificus developed contaminated painful cellulitis that progresses quickly as well as a marked local inflammation with signs of hemorrhaging. We described a case of Vibrio vulnificus sepsis, with emphasis on the clinical picture, the epidemiological background and lab findings; finally we did a brief review of the literature related to the case. PMID- 21982196 TI - [Clinical guideline for diagnosis and treatment of the thromboembolic venous disease]. AB - OBJECTIVE: To develop a guideline on thrombosis in order to standardize the protocol of management, as a strategy for reducing the morbidity and mortality. METHODS: Clinical questions were formulated and structured. Standardized sequence was established to search for practice guidelines from the clinical questions raised on diagnosis and treatment of venous thrombosis. The working group selected clinical practice guidelines. We choose seven guidelines with the best recommendations. For recommendations not included in the referenced guides the search process was conducted in PubMed and Cochrane Library. The results were expressed as levels of evidence and grade of recommendation. CONCLUSIONS: Risk criteria and the correct diagnosis can be established to choose thromboprophylaxis strategy. This guide is a compilation and an analysis of international guidelines, that meta-analysis and review articles on thrombosis that makes available to medical staff recommendations based on evidence to make decisions, standardized diagnostic and treatment to reduce morbidity and mortality in patients with venous thrombosis. PMID- 21982197 TI - [Doctor in medicine Juan de la Fuente and the first professor's chair at the Real y Pontificia Universidad de Mexico]. AB - In this paper, we analyze Juan de la Fuente's life and work. De la Fuente was a medical doctor with medical studies in Siguenza and Sevilla, minor Spanish universities at that time. Born in Mallorca, he came to New Spain in 1563 and later, he was the first professor in the new Faculty of Medicine in the Royal and Pontifical University of Mexico. His life could be considered as an example of a brilliant professional career developed by a Spanish Medical Doctor coming to the New World, in his case to Mexico. Being a doctor in the main Mexican hospitals, and caring for numerous and select patients. Also was selected as visitador and protomedico, important responsibilities in the regulation of medical practice and quality of medicaments. As a cultivated man, he was a typical case of a humanist. He not only was interested in medicine, but also in natural history, dialectics and philosophy, with a good knowledge of Latin, classical literature and so on. He won the first Medicine Cathedral in 1578 and continued in this place until his death. PMID- 21982198 TI - [The arrival of the surgeon Alonso Lopez de Hinojosos to New Spain]. AB - Alonso Lopez de Hinojosos was the most popular surgeon in New Spain during the 16th century. He wrote the first book of surgery in the New World in 1578 and managed the Native's Hospital in Mexico City for more than a decade. However, nowadays there is not enough information that supports what has been written about him. As original contribution, in this article is presented a document that describes the arrival of Alonso Lopez de Hinojosos to New Spain in 1564. Likewise, it is explained the cultural context of the surgery and the professional training of surgeons in the colonial period. PMID- 21982200 TI - Light triggered detection of aminophenyl phosphate with a quantum dot based enzyme electrode. AB - An electrochemical sensor for p-aminophenyl phosphate (pAPP) is reported. It is based on the electrochemical conversion of 4-aminophenol (4AP) at a quantum dot (QD) modified electrode under illumination. Without illumination no electron transfer and thus no oxidation of 4AP can occur. pAPP as substrate is converted by the enzyme alkaline phosphatase (ALP) to generate 4AP as a product. The QDs are coupled via 1,4-benzenedithiol (BDT) linkage to the surface of a gold electrode and thus allow potential-controlled photocurrent generation. The photocurrent is modified by the enzyme reaction providing access to the substrate detection. In order to develop a photobioelectrochemical sensor the enzyme is immobilized on top of the photo-switchable layer of the QDs. Immobilization of ALP is required for the potential possibility of spatially resolved measurements. Geometries with immobilized ALP are compared versus having the ALP in solution. Data indicate that functional immobilization with layer-by-layer assembly is possible. Enzymatic activity of ALP and thus the photocurrent can be described by Michaelis- Menten kinetics. pAPP is detected as proof of principle investigation within the range of 25 MUM-1 mM. PMID- 21982199 TI - Flexural strength and failure modes of layered ceramic structures. AB - OBJECTIVE: To evaluate the effect of the specimen design on the flexural strength (sigma(f)) and failure mode of ceramic structures, testing the hypothesis that the ceramic material under tension controls the mechanical performance of the structure. METHODS: Three ceramics used as framework materials for fixed partial dentures (YZ--Vita In-Ceram YZ; IZ--Vita In-Ceram Zirconia; AL--Vita In-Ceram AL) and two veneering porcelains (VM7 and VM9) were studied. Bar-shaped specimens were produced in three different designs (n=10): monolithic, two layers (porcelain-framework) and three layers (TRI) (porcelain-framework-porcelain). Specimens were tested for three-point flexural strength at 1MPa/s in 37 degrees C artificial saliva. For bi-layered design, the specimens were tested in both conditions: with porcelain (PT) or framework ceramic (FT) layer under tension. Fracture surfaces were analyzed using stereomicroscope and scanning electron microscopy (SEM). Young's modulus (E) and Poisson's ratio (nu) were determined using ultrasonic pulse-echo method. Results were statistically analyzed by Kruskal-Wallis and Student-Newman-Keuls tests. RESULTS: Except for VM7 and VM9, significant differences were observed for E values among the materials. YZ showed the highest nu value followed by IZ and AL. YZ presented the highest sigma(f). There was no statistical difference in the sigma(f) value between IZ and IZ-FT and between AL and AL-FT. sigma(f) values for YZ-PT, IZ-PT, IZ-TRI, AL-PT, AL-TRI were similar to the results obtained for VM7 and VM9. Two types of fracture mode were identified: total and partial failure. SIGNIFICANCE: The mechanical performance of the specimens was determined by the material under tension during testing, confirming the study hypothesis. PMID- 21982201 TI - Novel microwell-based spectrophotometric assay for determination of atorvastatin calcium in its pharmaceutical formulations. AB - The formation of a colored charge-transfer (CT) complex between atorvastatin calcium (ATR-Ca) as a n-electron donor and 2, 3-dichloro-5,6-dicyano-1,4 benzoquinone (DDQ) as a pi-electron acceptor was investigated, for the first time. The spectral characteristics of the CT complex have been described, and the reaction mechanism has been proved by computational molecular modeling. The reaction was employed in the development of a novel microwell-based spectrophotometric assay for determination of ATR-Ca in its pharmaceutical formulations. The proposed assay was carried out in 96-microwell plates. The absorbance of the colored-CT complex was measured at 460 nm by microwell-plate absorbance reader. The optimum conditions of the reaction and the analytical procedures of the assay were established. Under the optimum conditions, linear relationship with good correlation coefficient (0.9995) was found between the absorbance and the concentration of ATR-Ca in the range of 10-150 MUg/well. The limits of detection and quantitation were 5.3 and 15.8 MUg/well, respectively. No interference was observed from the additives that are present in the pharmaceutical formulation or from the drugs that are co-formulated with ATR-Ca in its combined formulations. The assay was successfully applied to the analysis of ATR-Ca in its pharmaceutical dosage forms with good accuracy and precision. The assay described herein has great practical value in the routine analysis of ATR-Ca in quality control laboratories, as it has high throughput property, consumes minimum volume of organic solvent thus it offers the reduction in the exposures of the analysts to the toxic effects of organic solvents, and reduction in the analysis cost by 50-fold. Although the proposed assay was validated for ATR-Ca, however, the same methodology could be used for any electron-donating analyte for which a CT reaction can be performed. PMID- 21982202 TI - A randomised clinical trial of the effect of low-level laser therapy for perineal pain and healing after episiotomy: a pilot study. AB - OBJECTIVE: to evaluate the effects of low-level laser therapy for perineal pain and healing after episiotomy. DESIGN: a double-blind, randomised, controlled clinical trial comparing perineal pain scores and episiotomy healing in women treated with low-level laser therapy (LLLT) and with the simulation of the treatment. SETTING: the study was conducted in the Birth Centre and rooming-in units of Amparo Maternal, a maternity service located in the city of Sao Paulo, Brazil. PARTICIPANTS: fifty-two postpartum women who had had mediolateral episiotomies during their first normal delivery were randomly divided into two groups of 26: an experimental group and a control group. INTERVENTION: in the experimental group, the women were treated with LLLT. Irradiation was applied at three points directly on the episiotomy after the suture and in three postpartum sessions: up to 2 hrs postpartum, between 20 and 24 hrs postpartum and between 40 and 48 hrs postpartum. The LLLT was performed with diode laser, with a wavelength of 660 nm (red light), spot size of 0.04 cm(2), energy density of 3.8 J/cm(2), radiant power of 15 mW and 10s per point, which resulted in an energy of 0.15 J per point and a total energy of 0.45 J per session. The control group participants also underwent three treatment sessions, but without the emission of radiation (simulation group), to assess the possible effects of placebo treatment. MAIN OUTCOMES: perineal pain scores, rated on a scale from 0 to 10, were evaluated before and immediately after the irradiation in the three sessions. The healing process was assessed using the REEDA scale (Redness, Edema, Echymosis, Discharge Aproximation) before each laser therapy session and 15 and 20 days after the women's discharge. FINDINGS: comparing the pain scores before and after the LLLT sessions, the experimental group presented a significant within-group reduction in mean pain scores after the second and third sessions (p=0.003 and p<0.001, respectively), and the control group showed a significant reduction after the first treatment simulation (p=0.043). However, the comparison of the perineal pain scores between the experimental and control groups indicated no statistical difference at any of the evaluated time points. There was no significant difference in perineal healing scores between the groups. All postpartum women approved of the low-level laser therapy. CONCLUSIONS: this pilot study showed that LLLT did not accelerate episiotomy healing. Although there was a reduction in perineal pain mean scores in the experimental group, we cannot conclude that the laser relieved perineal pain. This study led to the suggestion of a new research proposal involving another irradiation protocol to evaluate LLLT's effect on perineal pain relief. PMID- 21982203 TI - Attitudes towards complementary and alternative medicine in chronic pain syndromes: a questionnaire-based comparison between primary headache and low back pain. AB - BACKGROUND: Complementary and Alternative Medicine (CAM) is widely used and popular among patients with primary headache or low back pain (LBP). Aim of the study was to analyze attitudes of headache and LBP patients towards the use of CAM. METHODS: Two questionnaire-based surveys were applied comparing 432 primary headache and 194 LBP patients. RESULTS: In total, 84.75% of all patients reported use of CAM; with significantly more LBP patients. The most frequently-used CAM therapies in headache were acupuncture (71.4%), massages (56.4%), and thermotherapy (29.2%), in LBP thermotherapy (77.4%), massages (62.7%), and acupuncture (51.4%). The most frequent attitudes towards CAM use in headache vs. LBP: "leave nothing undone" (62.5% vs. 52.1%; p = 0.006), "take action against the disease" (56.8% vs. 43.2%; p = 0.006). Nearly all patients with previous experience with CAM currently use CAM in both conditions (93.6% in headache; 100% in LBP). However, the majority of the patients had no previous experience. CONCLUSION: Understanding motivations for CAM treatment is important, because attitudes derive from wishes for non-pharmacological treatment, to be more involved in treatment and avoid side effects. Despite higher age and more permanent pain in LBP, both groups show high use of CAM with only little specific difference in preferred methods and attitudes towards CAM use. This may reflect deficits and unfulfilled goals in conventional treatment. Maybe CAM can decrease the gap between patients' expectations about pain therapy and treatment reality, considering that both conditions are often chronic diseases, causing high burdens for daily life. PMID- 21982204 TI - Effect of tissue perfusion on microwave ablation: experimental in vivo study in porcine kidneys. AB - PURPOSE: To determine the effect of tissue perfusion on microwave ablation lesions in an experimental in vivo study in porcine kidneys. MATERIALS AND METHODS: Twelve kidneys of six pigs were studied. In each animal, two microwave ablations were created in one kidney without limitation of tissue perfusion (group 1). In the other kidney, two microwave ablations were performed with interruption of blood flow (group 2). All microwave ablations were performed with identical system parameters (eg, temperature control mode, ablation time of 80 s, and temperature of 110 degrees C). The animals were euthanized 3 hours later. The kidneys were harvested and cut into 2-3-mm transverse slices. Microwave ablation zone dimensions (eg, length, width, and volume) and shape (eg, sphericity ratio) and corresponding variability were compared between groups. RESULTS: Microwave ablation areas were significantly longer (41.6 mm +/- 4.0 vs 34.2 mm +/- 5.9; P < .01) and wider (16.6 mm +/- 1.2 vs 12.2 mm +/- 2.1; P < .001) in group 2 than in group 1. Similarly, microwave ablation volume was significantly greater in group 2 compared with group 1 (6.7 cm(3) +/- 1.0 vs 3.3 cm(3) +/- 1.2; P < .001). Ablation area shapes were similar between groups (sphericity ratio, 2.57 +/- 0.42 vs 2.39 +/- 0.34). Ablation area variabilities were also comparable between groups (volume variance of 1.32 vs 0.93; sphericity ratio variance of 0.18 vs 0.11). CONCLUSIONS: After interruption of blood flow, microwave ablation areas are significantly larger than those achieved without limitation of tissue perfusion. Microwave ablation area shape and variability were comparable between study groups. PMID- 21982206 TI - Efficacy of radiotherapy in the treatment of orbital pseudotumor: in regards to Matthiesen et al. (Int J Radiat Oncol Biol Phys 2011;79:1496-502). PMID- 21982207 TI - Re: Devic et al. (Int J Radiat Oncol Biol Phys 2010;78:1555-1562). PMID- 21982209 TI - Acquisition of spores on gloved hands after contact with the skin of patients with Clostridium difficile infection and with environmental surfaces in their rooms. AB - In a prospective study of 30 patients with Clostridium difficile infection, we found that acquisition of spores on gloved hands was as likely after contact with commonly touched environmental surfaces (ie, bed rail, bedside table, telephone, call button) as after contact with commonly examined skin sites (ie, chest, abdomen, arm, hand). PMID- 21982210 TI - Highly frequent infections with human rhinovirus in healthy young children: a longitudinal cohort study. AB - BACKGROUND: Human rhinoviruses (HRVs) are an important cause of respiratory tract infections. OBJECTIVES: We questioned whether the high prevalence rates of HRVs found in epidemiological studies is due to long-term individual continuity or a result of frequent infections with different HRV subtypes. STUDY DESIGN: In a 6 month winter period 18 healthy controls, aged 0-7 years, were at least sampled every two weeks for HRV-PCR, irrespective of respiratory symptoms. All HRV positive samples were genotyped to determine HRV diversity. RESULTS: In total 272 samples were collected. HRV was found in 101/272 (37%) samples. Genotyping revealed 27 different HRV subtypes. A median of 3.0 different HRV subtypes was found per child. Re-infections and continuity with identical HRV sequences were observed. The number of HRVs were higher in the youngest age group (p=0.01) and they had more different HRV subtypes (p=0.05) compared to oldest age group. CONCLUSIONS: We found a high HRV exposition with a considerable diverse population of HRV subtypes in young children. These results have major implications for future research into the pathogenic role of HRV in respiratory diseases. Characterisation of subtypes will be necessary to discriminate between prolonged continuity and re-infections in patients with respiratory diseases. PMID- 21982211 TI - Risk factors for Plasmodium falciparum hyperparasitaemia in malarious children. AB - BACKGROUND: Hyperparasitaemia is a feature of childhood severe malaria but there is little information on the risk factors for hyperparasitaemia in malarious children METHODS: The risk factors associated with Plasmodium falciparum hyperparasitaemia, defined as asexual parasitaemia > 250,000/MUl, at presentation were evaluated in 3338 malarious children enrolled prospectively between 2008 and 2010 in an endemic area of southwestern Nigeria. RESULTS: At enrolment, 97 (3%) of 3338 malarious children had hyperparasitaemia. In a multiple regression model, 3 factors were found to be independent risk factors for the presence of hyperparasitaemia at enrolment: an age <= 11 years (Adjusted odds ratio [AOR] = 2.85, 95% confidence interval [CI] 1.23-6.61, P = 0.014), fever (AOR = 2.02, 95% CI 1.23-3.29, P = 0.005), and enrolment after year 2008 (AOR = 0.42, 95% CI 0.24 0.73, P = 0.002). Duration of illness <= 3 d was associated with increased risk of hyperparasitaemia. There was no association between season and hyperparasitaemia. Compared to non-hyperparasitaemia, hyperparasitaemia was associated with an increased risk of progression to cerebral malaria (P < 0.0001). The risk of progression in hyperparasitaemic children was higher in < 5 year olds (P = 0.02). CONCLUSION: Young age and presence of fever are independent risk factors for hyperparasitaemia which is associated with an increased risk of progression to cerebral malaria. The findings have implications for case and community management of childhood hyperparasitaemia and for malaria control efforts in sub-Saharan Africa where severe malaria is relatively common. PMID- 21982212 TI - Cell adhesion control on photoreactive phospholipid polymer surfaces. AB - Non-invasive and effective cell recovery from culture substrates is important for the passage and characterization of cells. In this study, a photoreactive polymer surface, which uses UV-irradiation to control substrate cell adhesion, was prepared. The photoreactive phospholipid polymer (PMB-PL) reported herein, was composed of a both 2-methacryloyloxyethyl phosphorylcholine (MPC) unit as a cytocompatible unit and methacrylate bearing a photolabile nitrobenzyl group. The PMB-PL polymer was used to coat a cell culture substrate thus affording a photoreactive surface. Surface analysis of the PMB-PL coating indicated a strong photoresponse owing to the sensitivity of the PL unit. Before light exposure, the PMB-PL surface provided cell adhesion. Following UV-irradiation, the PMB-PL coating was converted to a neutral zeta-potential and hydrophilic surface. The photoreactive surface conversion process allowed for the detachment of adhered cells from the PMB-PL surface while maintaining cell viability. This study demonstrates the promise and significance of the PMB-PL photoreactive surface as a method to control cell attachment and detachment for cell function investigation. PMID- 21982213 TI - Factors affecting the formation of insulin amyloid spherulites. AB - Thermally induced amyloid aggregation of bovine insulin can produce a number of distinct aggregate morphologies. In this work amyloid spherulites were analysed using cross polarized optical microscopy and light scattering. A new semi quantitative methodology to estimate the balance of spherulites and free fibrils is reported and, from this analysis, the effects of pH, temperature, salt, and protein concentration on spherulite formation were quantitatively determined for the first time. The number and size of spherulites measured with polarized light microscopy were related to changes in the colloidal stability of the solution and fibril nucleation times (measured by static light scattering). Importantly, changes in pH between 1.75 and 2 were found to result in a dramatic decrease in the spherulite radii, which were related to differences in the conformational stability of the protein. Moreover, estimates of the final spherulite volume fraction clearly indicate that amyloid spherulite formation is the dominant pathway for insulin aggregation in HCl solutions at low pH and protein concentrations below ~5 mg ml(-1), with the balance shifting towards fibrils as the concentration increases. PMID- 21982214 TI - Spatiotemporally controlled navigation of neurite outgrowth in sequential steps on the dynamically photo-patternable surface. AB - A great number of the neurites interconnect neuronal cells in a brain to form the complicate neural circuits, whose structures are dynamically changed with changing the numbers and destinations of the neurites. Fabricating a model of neural network in vitro is one of the promising methods to precisely assay the signal transmission and processing within the circuit as well as to examine behaviors of individual cells. In this study, aiming to fabricate the dynamically alterable neural network in vitro, the chemically modified surface with the photo reactive self-assembled monolayer was applied to navigate the neurite outgrowth activities of differentiated PC12 cell in the spatially and temporally controlled manner. Numbers of the cell soma were effectively adhered and simultaneously arrayed according to the 25 MUm square patterns, which were easily fabricated with a single shot of the 365-nm ultraviolet (UV) irradiation and pre-coated with the extracellular matrix (ECM) protein. Narrow neurites were successively guided along the 5 MUm line patterns drawn on the surface by stepwise irradiation of the UV light in the intended designs and at appropriate timing. Sprouting number, elongating direction, bending, branching, and formation of autapse-like structure were controllable. The rate of neurite elongation was dependent on the ECM species, that were pre-coated beneath the cell soma, suggesting the ECM stimulated the basal side of the cell soma and affected the outgrowth process of the neurite. Navigation of the neurite elongation along the microline pattern for a primary rat brain cortex neuron was also achieved. PMID- 21982215 TI - Fabrication and morphology control of electrospun poly(gamma-glutamic acid) nanofibers for biomedical applications. AB - We report the fabrication of water-stable electrospun gamma-polyglutamic acid (gamma-PGA) nanofibers with morphology control for biomedical applications. In this study, the processing variables including polymer concentration, flow rate, applied voltage, collection distance, and ambient humidity were systematically optimized to generate uniform gamma-PGA nanofibers with a smooth morphology. By changing the trifluoroacetic acid concentration in the electrospinning solution, the diameter of the gamma-PGA nanofibers can be controlled within the range of 186-603 nm. To render the gamma-PGA nanofibers with good water stability, cystamine was employed as a crosslinking agent to amidate the carboxyl groups of gamma-PGA. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay in conjunction of cell morphology observation reveals that the obtained gamma-PGA nanofibers have an excellent biocompatibility to promote the cell adhesion and proliferation. We anticipate that the fabricated electrospun gamma-PGA nanofibers with controllable morphology and good water stability may find extensive applications in future development of tissue engineering scaffold materials, drug delivery systems, environmental remediation, and sensing. PMID- 21982216 TI - The mechanism of poly(ethylene glycol) 4000 effect on enzymatic hydrolysis of lignocellulose. AB - Adsorption of cellulase on substrates is a key step for enzymatic hydrolysis of lignocellulose. Addition of surface active additives affects the interaction between cellulase and substrates and has been proven to enhance enzymatic hydrolysis of lignocellulose by many studies. However, the mechanism of poly(ethylene glycol) effect is not yet clear. In this study, enzymatic activity and the adsorption of cellulase on different substrates with different addition sequence of PEG 4000 were investigated. The crystallinity index of substrates incubated by PEG 4000 was also measured by FTIR and XRD. Except for reduction of unproductive binding of cellulase on lignin which was reported by some literatures, current results confirmed a crucial function of PEG 4000 which prevented cellulase deactivation on cellulose rather than lignin through significant difference in adsorption capacity and enzymatic activity of cellulase with different PEG 4000 addition sequence. This conclusion rationally explained PEG 4000 had positive effect on pure cellulose without lignin as well as on lignocellulosic biomass. In addition, PEG 4000 was also found to be contributed to promote the removal of amorphous cellulose. These conclusions are helpful to understand the effect of surface active additives and optimize the enzymatic hydrolysis process. PMID- 21982217 TI - Silver nanoparticles formation using tyrosine in presence cetyltrimethylammonium bromide. AB - Upon addition of silver nitrate (precursor) to a solution of tyrosine (reductant) and cetlytrimethylammonium bromide (stabilizer), a transient species appears as the reaction time increases, which is stable for several months. The formation of silver nanoparticle was observed visually by color change (pale yellow to brownish yellow). In order to confirm the nature of the transient species, spectroscopic, kinetic, coagulation, transmission and scanning electron microscopic experiments were carried out. The reaction follows first-order kinetics with respect to [tyrosine] and [Ag(+)] under our experimental conditions. The phenolic -OH group of tyrosine is responsible for the reduction of Ag(+) ions. On the basis of various observations, the most plausible mechanism is proposed and discussed. PMID- 21982218 TI - Multiplex polymerase chain reaction method to detect Cyclospora, Cystoisospora, and Microsporidia in stool samples. AB - Cyclospora, Cystoisospora, and Microsporidia are eukaryotic enteropathogens that are difficult to detect in stool samples because they require special stains and microscopy. We developed a multiplex polymerase chain reaction (PCR) reaction with 4 primer sets to amplify Cyclospora cayetanensis, Cystoisospora belli, Enterocytozoon bieneusi, and Encephalitozoon intestinalis. Detection of the amplicon is through specific probes coupled to Luminex beads. Sensitivity of the assay was evaluated using Encephalitozoon intestinalis spores and revealed detection of 10(1) spores spiked into stool. No cross-reactivity was observed. We evaluated the assay on diarrheal specimens from Thailand, Tanzania, Indonesia, and the Netherlands that had been previously tested by microscopy, and the assay yielded 87-100% sensitivity and 88-100% specificity. Microscopy-negative/PCR positive samples had lower Luminex values, suggesting they were true but with lower burden infections. In summary, this is a convenient single PCR reaction that can detect Cyclospora, Cystoisospora, and Microsporidia without the need for cumbersome microscopic analysis. PMID- 21982219 TI - New insights into the induction of the heat shock proteins in baculovirus infected insect cells. AB - Eight members of the HSP/HSC70 family were identified in Spodoptera frugiperda Sf9 cells infected with Autographa californica multiple nucleopolyhedrovirus (AcMNPV) by 2D electrophoresis followed by mass spectrometry (MALDI/TOF) and a Mascot search. The family includes five HSP70s induced by AcMNPV-infection and three constitutive cognate HSC70s that remained abundant in infected cells. Confocal microscopy revealed dynamic changes in subcellular localization of HSP/HSC70s in the course of infection. At the early stages (4 to 10 hpi), a fraction of HSPs is localized in distinct speckles in cytoplasm. The speckles contained ubiquitinylated proteins suggesting that they may be aggresomes where proteins targeted by ubiquitin are sequestered or processed for proteolysis. S. frugiperda HSP90 was identified in the 2D gels by Western blotting. Its amount was unchanged during infection. A selective inhibitor of HSP90, 17-AAG, decreased the rate of viral DNA synthesis in infected cells suggesting a supportive role of HSP90 in virus replication. PMID- 21982220 TI - Inhibition of the epidermal growth factor receptor by erlotinib prevents immortalization of human cervical cells by Human Papillomavirus type 16. AB - The Human Papillomavirus type-16 (HPV-16) E6 and E7 oncogenes are selectively retained and expressed in cervical carcinomas, and expression of E6 and E7 is sufficient to immortalize human cervical epithelial cells. Expression of the epidermal growth factor receptor (EGFR) is often increased in cervical dysplasia and carcinoma, and HPV oncoproteins stimulate cell growth via the EGFR pathway. We found that erlotinib, a specific inhibitor of EGFR tyrosine kinase activity, prevented immortalization of cultured human cervical epithelial cells by the complete HPV-16 genome or the E6/E7 oncogenes. Erlotinib stimulated apoptosis in cells that expressed HPV-16 E6/E7 proteins and induced senescence in a subpopulation of cells that did not undergo apoptosis. Since immortalization by HPV E6/E7 is an important early event in cervical carcinogenesis, the EGFR is a potential target for chemoprevention or therapy in women who have a high risk for cervical cancer. PMID- 21982221 TI - In vivo hypermutation of xenotropic murine leukemia virus-related virus DNA in peripheral blood mononuclear cells of rhesus macaque by APOBEC3 proteins. AB - The gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV), replicates to high titers in some human cell lines and is able to infect non human primates. To determine whether APOBEC3 (A3) proteins restrict XMRV infections in a non-human primate model, we sequenced proviral DNA from peripheral blood mononuclear cells of XMRV-infected rhesus macaques. Hypermutation characteristic of A3DE, A3F and A3G activities was observed in the XMRV proviral sequences in vivo. Furthermore, expression of rhesus A3DE, A3F, or A3G in human cells inhibited XMRV infection and caused hypermutation of XMRV DNA. These studies show that some rhesus A3 isoforms are highly effective against XMRV in the blood of a non-human primate model of infection and in cultured human cells. PMID- 21982222 TI - Lung glutathione adaptive responses to cigarette smoke exposure. AB - BACKGROUND: Smoking tobacco is a leading cause of chronic obstructive pulmonary disease (COPD), but although the majority of COPD cases can be directly related to smoking, only a quarter of smokers actually develop the disease. A potential reason for the disparity between smoking and COPD may involve an individual's ability to mount a protective adaptive response to cigarette smoke (CS). Glutathione (GSH) is highly concentrated in the lung epithelial lining fluid (ELF) and protects against many inhaled oxidants. The changes in GSH that occur with CS are not well investigated; therefore the GSH adaptive response that occurs with a commonly utilized CS exposure was examined in mice. METHODS: Mice were exposed to CS for 5 h after which they were rested in filtered air for up to 16 h. GSH levels were measured in the ELF, bronchoalveolar lavage cells, plasma, and tissues. GSH synthesis was assessed by measuring gamma-glutamylcysteine ligase (GCL) activity in lung and liver tissue. RESULTS: GSH levels in the ELF, plasma, and liver were decreased by as much as 50% during the 5 h CS exposure period whereas the lung GSH levels were unchanged. Next, the time course of rebound in GSH levels after the CS exposure was examined. CS exposure initially decreased ELF GSH levels by 50% but within 2 h GSH levels rebound to about 3 times basal levels and peaked at 16 h with a 6-fold increase and over repeat exposures were maintained at a 3-fold elevation for up to 2 months. Similar changes were observed in tissue GCL activity which is the rate limiting step in GSH synthesis. Furthermore, elevation in ELF GSH levels was not arbitrary since the CS induced GSH adaptive response after a 3d exposure period prevented GSH levels from dropping below basal levels. CONCLUSIONS: CS exposures evoke a powerful GSH adaptive response in the lung and systemically. These data suggests there may be a sensor that sets the ELF GSH adaptive response to prevent GSH levels from dipping below basal levels. Factors that disrupt GSH adaptive responses may contribute to the pathophysiology of COPD. PMID- 21982223 TI - Long live sox2: sox2 lasts a lifetime. AB - Sox2 is a key transcription factor required for the maintenance of pluripotency in embryonic cells and morphogenesis of several epithelia. In this issue of Cell Stem Cell, Arnold et al. (2011) demonstrate that Sox2 marks long-lived adult stem cells to ensure homeostasis in a broad range of adult tissues. PMID- 21982224 TI - eNERgizing pluripotent gene transcription. AB - Nucleotide excision repair proteins are classically associated with DNA repair. However, a study by Fong et al. (2011) in the most recent issue of Cell demonstrates that the XPC/RAD23B/CETN2 nucleotide excision repair complex additionally functions as a transcriptional coactivator of Oct4/Sox2, critically regulating maintenance and reestablishment of stem cell pluripotency. PMID- 21982225 TI - New neurons maintain efficient stress recovery. AB - Adult neurogenesis has been the focus of intense investigation, but the function of new neurons remains elusive. Snyder et al. (2011) report that new neurons in the hippocampus play an important role in appropriate shut-off of the stress response. PMID- 21982226 TI - Not so lonely at the top for cancer stem cells. AB - A subpopulation of cancer cells is believed to be responsible for tumor initiation, propagation, and metastasis. In this issue of Cell Stem Cell, Dieter et al. (2011) show that these functions in colon cancer can be ascribed to distinct tumor-initiating cell populations. PMID- 21982227 TI - A panel of glycan cell surface markers define pluripotency state and promote safer cell-based therapies. AB - In a recent study in Nature Biotechnology, Tang et al. (2011) describe a new marker of pluripotency, stage-specific embryonic antigen-5 (SSEA-5), and show that this oligosaccharide, together with two other surface antigens, can be used to remove all tumor-initiating cells from prospective cell transplants. PMID- 21982228 TI - Impracticality of egg donor recruitment in the absence of compensation. PMID- 21982229 TI - Moving human SCNT research forward ethically. AB - A recent study of human somatic cells reprogrammed to a pluripotent state via somatic cell nuclear transfer (SCNT) will undoubtedly renew interest in human egg procurement. Thus it is imperative that human SCNT research move forward under stringent ethical standards in locales permitting directed egg donation for stem cell research. PMID- 21982230 TI - Metabolic regulation of hematopoietic stem cells in the hypoxic niche. AB - Tissue homeostasis over the life of an organism relies on both self-renewal and multipotent differentiation of stem cells. Hematopoietic stem cells (HSCs) reside in a hypoxic bone marrow environment, and their metabolic status is distinct from that of their differentiated progeny. HSCs generate energy mainly via anaerobic metabolism by maintaining a high rate of glycolysis. This metabolic balance promotes HSC maintenance by limiting the production of reactive oxygen species, but leaves HSCs susceptible to changes in redox status. In this review, we discuss the importance of oxygen homeostasis and energy metabolism for maintenance of HSC function and long-term self-renewal. PMID- 21982232 TI - Sox2(+) adult stem and progenitor cells are important for tissue regeneration and survival of mice. AB - The transcription factor Sox2 maintains the pluripotency of early embryonic cells and regulates the formation of several epithelia during fetal development. Whether Sox2 continues to play a role in adult tissues remains largely unknown. We show here that Sox2 marks adult cells in several epithelial tissues where its expression has not previously been characterized, including the stomach, cervix, anus, testes, lens, and multiple glands. Genetic lineage tracing and transplantation experiments demonstrate that Sox2-expressing cells continuously give rise to mature cell types within these tissues, documenting their self renewal and differentiation potentials. Consistent with these findings, ablation of Sox2(+) cells in mice results in a disruption of epithelial tissue homeostasis and lethality. Developmental fate mapping reveals that Sox2(+) adult stem cells originate from fetal Sox2(+) tissue progenitors. Thus, our results identify Sox2 expression in numerous adult endodermal and ectodermal stem cell compartments, which are critical for normal tissue regeneration and survival. PMID- 21982233 TI - Cripto regulates hematopoietic stem cells as a hypoxic-niche-related factor through cell surface receptor GRP78. AB - Hematopoietic stem cells (HSCs) are maintained in hypoxic niches in endosteal regions of bones. Here we demonstrate that Cripto and its receptor GRP78 are important regulators of HSCs in the niche. Flow cytometry analyses revealed two distinct subpopulations of CD34(-)KSL cells based on the expression of GRP78, and these populations showed different reconstitution potential in transplantation assays. GRP78(+)HSCs mainly reside in the endosteal area, are more hypoxic, and exhibit a lower mitochondrial potential, and their HSC capacity was maintained in vitro by Cripto through induction of higher glycolytic activity. Additionally, HIF-1alpha KO mice have decreased numbers of GRP78(+)HSCs and reduced expression of Cripto in the endosteal niche. Furthermore, blocking GRP78 induced a movement of HSCs from the endosteal to the central marrow area. These data suggest that Cripto/GRP78 signaling is an important pathway that regulates HSC quiescence and maintains HSCs in hypoxia as an intermediary of HIF-1alpha. PMID- 21982234 TI - Canonical wnt signaling regulates hematopoiesis in a dosage-dependent fashion. AB - Canonical Wnt signaling has been implicated in the regulation of hematopoiesis. By employing a Wnt-reporter mouse, we observed that Wnt signaling is differentially activated during hematopoiesis, suggesting an important regulatory role for specific Wnt signaling levels. To investigate whether canonical Wnt signaling regulates hematopoiesis in a dosage-dependent fashion, we analyzed the effect of different mutations in the Adenomatous polyposis coli gene (Apc), a negative modulator of the canonical Wnt pathway. By combining different targeted hypomorphic alleles and a conditional deletion allele of Apc, a gradient of five different Wnt signaling levels was obtained in vivo. We here show that different, lineage-specific Wnt dosages regulate hematopoietic stem cells (HSCs), myeloid precursors, and T lymphoid precursors during hematopoiesis. Differential, lineage specific optimal Wnt dosages provide a unifying concept that explains the differences reported among inducible gain-of-function approaches, leading to either HSC expansion or depletion of the HSC pool. PMID- 21982235 TI - Distinct types of tumor-initiating cells form human colon cancer tumors and metastases. AB - Human colon cancer harbors a small subfraction of tumor-initiating cells (TICs) that is assumed to be a functionally homogeneous stem-cell-like population driving tumor maintenance and metastasis formation. We found unexpected cellular heterogeneity within the TIC compartment, which contains three types of TICs. Extensively self-renewing long-term TICs (LT-TICs) maintained tumor formation in serial xenotransplants. Tumor transient amplifying cells (T-TACs) with limited or no self-renewal capacity contributed to tumor formation only in primary mice. Rare delayed contributing TICs (DC-TICs) were exclusively active in secondary or tertiary mice. Bone marrow was identified as an important reservoir of LT-TICs. Metastasis formation was almost exclusively driven by self-renewing LT-TICs. Our results demonstrate that tumor initiation, self-renewal, and metastasis formation are limited to particular subpopulations of TICs in primary human colon cancer. We identify LT-TICs as a quantifiable target for therapies aimed toward eradication of self-renewing tumorigenic and metastatic colon cancer cells. PMID- 21982236 TI - Genome sequencing of mouse induced pluripotent stem cells reveals retroelement stability and infrequent DNA rearrangement during reprogramming. AB - The biomedical utility of induced pluripotent stem cells (iPSCs) will be diminished if most iPSC lines harbor deleterious genetic mutations. Recent microarray studies have shown that human iPSCs carry elevated levels of DNA copy number variation compared with those in embryonic stem cells, suggesting that these and other classes of genomic structural variation (SV), including inversions, smaller duplications and deletions, complex rearrangements, and retroelement transpositions, may frequently arise as a consequence of reprogramming. Here we employ whole-genome paired-end DNA sequencing and sensitive mapping algorithms to identify all classes of SV in three fully pluripotent mouse iPSC lines. Despite the improved scope and resolution of this study, we find few spontaneous mutations per line (one or two) and no evidence for endogenous retroelement transposition. These results show that genome stability can persist throughout reprogramming, and argue that it is possible to generate iPSCs lacking gene-disrupting mutations using current reprogramming methods. PMID- 21982238 TI - [The pathologist as seen by the gastroenterologist: the oracle and the censor]. PMID- 21982237 TI - Progress in endocrine approaches to the treatment and prevention of breast cancer. AB - Tamoxifen had been the only available hormonal option for the systemic treatment for breast cancer from 1973 to 2000. Enormous efforts have led to the development of potent and selective third generation aromatase inhibitors including anastrozole, letrozole and exemestane. Due to their superior efficacy to tamoxifen, aromatase inhibitors are presently approved as first line agents for the treatment of advanced estrogen receptor (ER) positive breast cancer and adjuvant therapy in early ER positive early breast cancer in postmenopausal women. Selective ER Modulators (SERMS), tamoxifen and raloxifene are the only agents presently used in breast cancer prevention in high risk women and their use has increased substantially over the last decade. Third generations SERMS, lasofoxifene and bazedoxifene have shown significant reduction in bone loss compared to placebo in postmenopausal women and are currently approved in the European Union for the treatment of postmenopausal osteoporosis. This review outlines the current strategies employed in the use of endocrine therapy in the management and prevention of breast cancer. PMID- 21982239 TI - [Micro-invasive vulvar Paget's disease and lymph node metastasis: a same disease?]. AB - Vulvar Paget's disease is sub-classified into three types based upon its origin. It might be a primary vulvar disease (type 1) or associated with a non-cutaneous adenocarcinoma-rectal, colonic, cervical (type 2) or linked with an urothelial neoplasia (type 3). Type 1lesions must be considered as potentially invasive. Their immunophenotype is CK7+/CK20-. Classically, in case of depth of invasion below 1mm, nodal metastases are exceptional. We report a case of type 1 Paget's disease in a postmenopausal woman with superficial invasion and multiple inguinal nodal metastases. PMID- 21982240 TI - [Fallopian tube: the dark face of pelvic carcinogenesis]. AB - Ovarian carcinomas are a heterogeneous group of lesions, among which serous histologic subtype is the most frequent. Ovarian and peritoneal serous carcinomas are subdivided into low- and high-grade tumors. Low-grade carcinomas derive from serous tumors of low malignant potentiel, while high-grade carcinomas were thought to derive de novo from ovarian surface epithelium. Studies from prophylactic salpingo-oophorectomy in women with BRCA mutations revealed a precursor to pelvic serous carcinomas that originates in the distal fallopian tube, called STIC (serous tubal intraepithelial carcinoma). This review reports new findings on serous carcinogenesis in the tube (SCAT). It brings an explanation in French on different terminologies used in the English literature these last years such as SCOUT (secretory cell outgrowth), p53 signature, TILT (tubal intraepithelial lesion in transition), STIC and SCAT and on the macroscopic protocol of Brigham and Women's Hospital of annexectomies specially in the setting of BRCA mutation, the SEE-FIM (sectioning and extensively examining the fimbriated end of the fallopian tube). PMID- 21982241 TI - [Oesophageal and gastric pathology: early neoplastic lesions: introduction]. PMID- 21982242 TI - [Oesophageal and gastric pathology: early neoplastic lesions. case 1: squamous intraepithelial neoplasia of the oesophagus]. PMID- 21982243 TI - [Oesophageal and gastric pathology: early neoplastic lesions. case 2 and case 3. Dysplasia and superficial cancer on Barrett's oesophagus]. PMID- 21982244 TI - [Oesophageal and gastric pathology: early neoplastic lesions. case 4: a mesenchymal tumour of the lower oesophagus]. PMID- 21982245 TI - [High-grade gastric intra-epithelial neoplasia (or dysplasia) treated by endoscopic mucosal resection]. PMID- 21982246 TI - [Case n(o) 6: Signet ring cell intramucosal carcinoma in hereditary diffuse gastric cancer with mutated CDH1 gene]. PMID- 21982247 TI - [Oesophageal and gastric pathology: early neoplastic lesions: case no. 7: pyloric adenoma of the stomach]. PMID- 21982248 TI - [Oesophageal and gastric pathology: early neoplastic lesions: case n(o) 8: an endocrine tumour of the stomach]. PMID- 21982249 TI - [An unusual lesion of the nasopharynx: oncocytic metaplasia]. AB - Oncocytic metaplasia of the nasopharynx is an exceptional lesion which exact etiopathogenesis, although largely discussed, still remains controversial. The purpose of this paper is to present the epidemiological characteristics and clinical signs of this lesion and to study its pathogenesis and its therapeutic modalities. We report two cases that occurred respectively in a 53- and 60-year old woman. The first presented with pharyngeal dysesthesia and otalgia. The endoscopic examination revealed an irregularity of the posterior wall of the nasopharynx. The second patient presented with tinnitus, discomfort of the left ear and bilateral hearing loss. Endoscopic exam revealed a bilateral structural abnormality to the eardrum. Microscopy showed focal oncocytic metaplasia of the nasopharynx mucosa in both cases. There was a positive outcare for both patients after excisional biopsy. Oncocytic metaplasia seems to be in relation to the stimulation of sympathic neuropeptidergic nerve fibers which target epithelial, connective, endothelial and lymphoid cells. PMID- 21982250 TI - [Breast carcinoma metastasis into a renal cell carcinoma]. AB - We report the case of a patient carrying a right breast carcinoma whose imaging exams showed lung and bone metastasic release, and incidentally synchronous right renal tumor. Histologic examination of the renal tumor found a mammary carcinoma metastasis into a clear renal cell carcinoma. This is the second case report of breast cancer with metastasis in a resected renal clear cell carcinoma. PMID- 21982251 TI - [A recurring parotid tumor]. PMID- 21982252 TI - [An exceptional tumor of the vena cava]. PMID- 21982253 TI - [Vascular tumors and pseudotumors: introduction]. PMID- 21982254 TI - Age-related production of osteoclasts and the changes of serum levels of vascular endothelial growth factor (VEGF) and receptor activator for nuclear factor (NF) kappaB ligand (RANKL) in osteopetrotic (op/op) mice. AB - OBJECTIVE: Expression of osteoclasts in osteopetrotic (op/op) mice is substantially reduced by the absence of functional macrophage colony-stimulating factor (M-CSF). However, it has been reported that osteoclasts do gradually appear in the bones of op/op mice and spontaneously correct the osteopetrosis. DESIGN: Age-related production of osteoclasts and the changes of serum levels of vascular endothelial growth factor (VEGF) and receptor activator for nuclear factor (NF)-kappaB ligand (RANKL) in op/op mice were examined. RESULTS: The number of femoral osteoclasts, and the serum levels of VEGF, both gradually increased in op/op mice after birth and reached a peak in 120- and 60-day-old mice, respectively. However, the serum levels of RANKL showed an inverse relationship to osteoclast number. CONCLUSIONS: These findings suggest that the appearance of osteoclasts may be influenced by the serum levels of VEGF and that the serum levels of RANKL may be influenced by the appearance of osteoclasts. PMID- 21982255 TI - Dostoevsky's epilepsy: a new approach to retrospective diagnosis. AB - There has been considerable debate about Fyodor Dostoevsky's epilepsy. Was his epilepsy generalized or focal? Was the dramatic ecstatic experience an epileptic phenomenon or a literary invention? We compared probable epileptically related behavioral manifestations in The Idiot with experiences of current patients, studied with a modern interdisciplinary approach involving neurosurgery, neurology, and neuropsychiatry. Patients were studied by all disciplines starting with their initial evaluation and trial of antiseizure medication, during hospitalization for long-term monitoring for epilepsy at scalp and depth levels with electrical brain stimulation, during intraoperative interviews, and in long term postoperative follow-up. Behavioral manifestations, clearly shown to be phenomena of the epilepsy in our patients, were the template for defining the epileptic nature of the behavioral symptomatology described by Dostoevsky in his literary character, Prince Myshkin. We conclude that Dostoevsky had temporolimbic epilepsy and that the ecstatic experience is an epileptic phenomenon. PMID- 21982257 TI - Spinal tuberculosis. PMID- 21982256 TI - Non-specific low back pain. AB - Non-specific low back pain has become a major public health problem worldwide. The lifetime prevalence of low back pain is reported to be as high as 84%, and the prevalence of chronic low back pain is about 23%, with 11-12% of the population being disabled by low back pain. Mechanical factors, such as lifting and carrying, probably do not have a major pathogenic role, but genetic constitution is important. History taking and clinical examination are included in most diagnostic guidelines, but the use of clinical imaging for diagnosis should be restricted. The mechanism of action of many treatments is unclear, and effect sizes of most treatments are low. Both patient preferences and clinical evidence should be taken into account for pain management, but generally self management, with appropriate support, is recommended and surgery and overtreatment should be avoided. PMID- 21982259 TI - Compliance with sharps waste standards by a sample of Sydney acupuncture premises. AB - AIM: To examine current practices with regard to the safe collection, storage and disposal of sharps waste in acupuncture premises and to determine compliance with the NSW Public Health (Skin Penetration) Regulation 2000 and the NSW Health Skin Penetration Code of Best Practice. METHODS: A random sample of acupuncturists in the City of Sydney local government area was selected and surveyed using a structured questionnaire. RESULTS: All 26 acupuncturists surveyed had sharps disposal bins and complied with the Regulation, but the following elements of the Code were not uniformly followed: regular disposal of sharps (77%), disposal through a waste contractor (23%) and placement of bins out of reach of visitors (8%). CONCLUSION: Regular disposal of sharps containers in acupuncture premises could be improved. PMID- 21982260 TI - Increased presentations to emergency departments for asthma associated with rye grass pollen season in inland NSW. AB - AIM: This study measured the frequency and geographical extent of peaks in asthma presentations to emergency departments in inland NSW; it assessed the characteristics of patients who presented at peak presentation times during the rye grass pollination season (October-November) and at other times of the year. METHODS: Data describing over 13 years of daily emergency department presentations with a provisional diagnosis of asthma at nine inland NSW base hospitals were assembled. Days of counts in the top 0.1 percentile for each emergency department were classified as peak asthma count days. RESULTS: While the rye grass pollen season accounts for only 17% of days in the year, 53% of peak asthma count days fell within that period. Patients aged over 14 years represented 74% of visits on peak asthma count days during the pollen season and 50% on peak days at other times of the year. DISCUSSION: Under the right climatic conditions, rye grass pollen may be responsible for presentations for acute asthma to emergency departments in inland NSW. PMID- 21982261 TI - Bug breakfast in the bulletin: respiratory syncytial virus. PMID- 21982262 TI - Factsheet: Hendra virus. PMID- 21982263 TI - Communicable Diseases Report, NSW, May and June 2011. PMID- 21982264 TI - Introducing a new sexually transmissible infections contact tracing resource for use in NSW General Practice. PMID- 21982265 TI - Effect of Body Mass Index on work related musculoskeletal discomfort and occupational stress of computer workers in a developed ergonomic setup. AB - BACKGROUND: Work urgency, accuracy and demands compel the computer professionals to spend longer hours before computers without giving importance to their health, especially body weight. Increase of body weight leads to improper Body Mass Index (BMI) may aggravate work related musculoskeletal discomfort and occupational psychosocial stress. The objective of the study was to find out the effect of BMI on work related musculoskeletal discomforts and occupational stress of computer workers in a developed ergonomic setup. METHODS: A descriptive inferential study has been taken to analyze the effect of BMI on work related musculoskeletal discomfort and occupational-psychosocial stress. A total of 100 computer workers, aged 25-35 years randomly selected on convenience from software and BPO companies in Bangalore city, India for the participation in this study. BMI was calculated by taking the ratio of the subject's height (in meter) and weight (in kilogram). Work related musculoskeletal discomfort and occupational stress of the subjects was assessed by Cornell University's musculoskeletal discomfort questionnaire (CMDQ) and occupational stress index (OSI) respectively as well as a relationship was checked with their BMI. RESULTS: A significant association (p < 0.001) was seen among high BMI subjects with their increase scores of musculoskeletal discomfort and occupational stress. CONCLUSION: From this study, it has been concluded that, there is a significant effect of BMI in increasing of work related musculoskeletal discomfort and occupational-psychosocial stress among computer workers in a developed ergonomic setup. PMID- 21982266 TI - Mandibular reconstruction using extraoral trifocal bone transport: report of a case using a new device. PMID- 21982267 TI - Anti-inflammatory and antioxidant effects of Tualang honey in alkali injury on the eyes of rabbits: experimental animal study. AB - BACKGROUND: Alkali injury is one of the most devastating injuries to the eye. It results in permanent unilateral or bilateral visual impairment. Chemical eye injury is accompanied by an increase in the oxidative stress. Anti-inflammatory and antioxidant agents play a major role in the treatment of chemical eye injuries. The purpose of this study is to evaluate the anti-inflammatory (clinical and histopathological) and antioxidant effects of Tualang honey versus conventional treatment in alkali injury on the eyes of rabbits. METHODS: A preliminary study was carried out prior to the actual study to establish the alkali chemical injury on rabbit's cornea and we found that alkali chemical injury with 2 N NaOH showed severe clinical inflammatory features. In actual study, alkali injury with 2 N NaOH was induced in the right eye of 10 New Zealand White rabbits' cornea. The rabbits were divided into two groups, Group A was given conventional treatment and Group B was treated with both topical and oral Tualang honey. Clinical inflammatory features of the right eye were recorded at 12 hours, 24 hours, 72 hours, 5th day and 7th day post induction of alkali burn on the cornea. The histopathological inflammatory features of the right corneas of all rabbits were also evaluated on day-7. The level of total antioxidant status and lipid peroxidation products in the aqueous humour, vitreous humour and serum at day-7 were estimated biochemically. Fisher's Exact, Chi-Square and Mann Whitney test were used to analyse the data. RESULTS: There was no statistically significant difference in clinical inflammatory features (p > 0.05) between honey treated and the conventional treated group at different times of examination. Histopathological examination of the cornea showed the number of polymorphonuclear leucocytes was below 50 for both groups (mild grade). There was also no significant difference in the level of total antioxidant status as well as lipid peroxidation products in aqueous humour (p = 0.117, p = 0.382 respectively), vitreous humour (p = 0.917, p = 0.248 respectively) and serum (p = 0.917, p = 0.332 respectively) between honey treated and the conventional treated group. CONCLUSION: Tualang honey has almost the equal effects when compared with the conventional treatment in treating alkali injury on rabbit's eye. Future research with more number of rabbits and control group is warranted to explore the anti-inflammatory and antioxidant effects of Tualang honey. PMID- 21982268 TI - Dolichoectasic anterior cerebral artery and hemodynamics. AB - Dolichoectasia of the intracranial arteries is a rare condition, and the vertebrobasilar system and the internal carotid artery are the most commonly involved structures. We report a rare case of idiopathic dolichoectasia of the anterior cerebral artery in a 22-year-old female. The patient caused an automobile accident and was brought to our hospital in an ambulance. A computed tomography scan and magnetic resonance imaging revealed no fresh lesions, but showed a prominent serpentine structure with calcification and flow void in the region of the interhemispheric fissure, which was suspicious for arteriovenous malformation or arteriovenous fistula. Cerebral angiography demonstrated extensive dilatation of the anterior cerebral artery, but no evidence of arteriovenous malformation or arteriovenous fistula. Single photon emission computed tomography revealed hypoperfusion of the right frontal lobe at rest. Electroencephalography showed no epileptic discharge. The patient's course was uneventful, and she was discharged with no neurologic deficit. There are few reports of hemodynamic changes in cases of dolichoectasia. In the diagnosis of cerebral dolichoectasia, cerebral hemodynamics should be examined carefully in addition to evaluating vascular disease by angiography. PMID- 21982269 TI - The acceptance of in silico models for REACH: Requirements, barriers, and perspectives. AB - In silico models have prompted considerable interest and debate because of their potential value in predicting the properties of chemical substances for regulatory purposes. The European REACH legislation promotes innovation and encourages the use of alternative methods, but in practice the use of in silico models is still very limited. There are many stakeholders influencing the regulatory trajectory of quantitative structure-activity relationships (QSAR) models, including regulators, industry, model developers and consultants. Here we outline some of the issues and challenges involved in the acceptance of these methods for regulatory purposes. PMID- 21982270 TI - Kidney transplant survival in pediatric and young adults. AB - BACKGROUND: There is a perception that kidney transplant recipients transferred from pediatric centers to adult care have an increased risk of graft loss. It is not clear whether young adults transplanted in adult centers also suffer from high graft loss rates. METHODS: We examined death censored graft survival in 3 cohorts of young patients transplanted at a single center. Pediatric (PED) patients transplanted at the pediatric center were compared to a cohort of young adults (YAD; age 18- < 25) and a cohort of adults (ADL; age 25-35). RESULTS: In a multivariate Cox model for death-censored graft survival, PED survival was statistically similar to the YAD (HR 0.86, 95% CI 0.44, 1.7, p = 0.66), however the ADL cohort (HR 0.45, 95% CI 0.25, 0.82, p = 0.009) demonstrated better survival. Admitted non-adherence rates were not different among cohorts. Patients were transferred within a narrow age window (18.6 +/- 1.0 age in years) but at a wide range of times from the date of transplantation (5.1 +/- 3.5 years) and with a wide range of graft function (serum creatinine 182 +/- 81 MUmol/L). CONCLUSIONS: The perception that pediatric transfers do poorly reflects advanced graft dysfunction in some at the time of transfer. The evidence also suggests that it is not the transfer of care that is the critical issue but rather recipients, somewhere between the ages of 11-14 and 25, are a unique and vulnerable cohort. Effective strategies to improve outcomes across this age group need to be identified and applied consistently. PMID- 21982271 TI - [Hemihypertrophy and scoliosis revealing a Chiari 1 malformation with syringomyelia]. AB - We report the case of a 9-year-old boy with progressive thoracic scoliosis and crossed hemihypertrophy who was discovered with a Chiari 1 malformation and syringomyelia. These disorders are connected by complex physiopathological mechanisms; their association deserves attention. This observation reviews the importance of the clinical examination, particularly the neurological exam, in childhood scoliosis. The features suggesting a neurogenic background of spine deformation should be sought. Scoliosis with hemihypertrophy can be the sign of an underlying neurological abnormality. PMID- 21982272 TI - Ki-67 and minichromosome maintenance-7 (MCM7) expression in canine pituitary corticotroph adenomas. AB - Pituitary-dependent hyperadrenocorticism (PDH) caused by pituitary corticotroph adenoma is a common endocrine disorder in dogs. The ratio between pituitary height and the area of the brain (P/B) has been used to evaluate the pituitary size. A P/B ratio > 0.31 indicates an enlarged pituitary, whereas a P/B ratio <= 0.31 indicates a nonenlarged pituitary. The aim of this study was to investigate the expression of proliferation markers Ki-67 and minichromosome maintenance-7 (MCM7) in canine corticotroph adenomas in enlarged and in nonenlarged pituitaries and to evaluate their relation with the size of canine pituitary corticotroph adenomas. Ki-67 and MCM7 expression in ACTH-positive tumor cells was determined by dual-labeling immunohistochemistry in resected corticotroph adenomas from 15 dogs with PDH. The mean +/- SD Ki-67 labeling index (LI) was 0.55% +/- 0.59% in corticotroph adenomas with nonenlarged pituitaries and 1.6% +/- 0.6% in adenomas with enlarged pituitaries. The MCM7 LI in corticotroph adenomas with nonenlarged pituitaries and in adenomas with enlarged pituitaries was 2.9% +/- 2.2% and 10.9% +/- 3.7%, respectively. The Ki-67 LI and MCM7 LI were significantly greater in the adenomas with enlarged pituitaries than in the adenomas with nonenlarged pituitaries (P < 0.01 and P < 0.01, respectively). The MCM7 LI was significantly greater than the Ki-67 LI in adenomas (P < 0.01). The Ki-67 LI was positively correlated with the MCM7 LI (r = 0.820, P < 0.01), and the P/B ratio was positively correlated with the Ki-67 LI (r = 0.560, P = 0.03) and the MCM7 LI (r = 0.854, P < 0.01). In conclusion, canine corticotroph adenomas in enlarged pituitaries show greater proliferation potential than do adenomas in nonenlarged pituitaries. MCM7 expression was significantly greater than Ki-67 expression in canine pituitary corticotroph adenomas. Thus, MCM7 may be superior to Ki-67 as a proliferation marker in pituitary tumors. PMID- 21982273 TI - Comprehensive analysis of clinical significance of stem-cell related factors in renal cell cancer. AB - BACKGROUND: C-MYC, LIN28, OCT4, KLF4, NANOG and SOX2 are stem cell related factors. We detected whether these factors express in renal cell carcinoma (RCC) tissues to study their correlations with the clinical and pathological characteristics. METHODS: The expressions of c-MYC, LIN28, SOX2, KLF4, OCT4 and NANOG in 30 RCC patients and 5 non-RCC patients were detected with quantitative real-time reverse transcription-PCR (qRT-PCR). The data were analyzed with Wilcoxon signed rank sum test and x2 test. RESULTS: In RCC group, c-MYC expression was significantly higher in RCC tissues compared with normal tissues (P < 0.05). The expression levels of OCT4, KLF4, NANOG and SOX2 were significantly lower in RCC tissues compared with normal tissues (P < 0.05). LIN28 expression level was not significant. No difference was observed when it comes to clinical and pathological characteristics such as gender, age, tumor size, cTNM classification and differentiation status (P > 0.05). Also the expression levels of all above factors were not significantly changed in non-RCC group (P > 0.05). CONCLUSIONS: The present analysis strongly suggests that altered expression of several stem cell related factors may play different roles in RCC. C-MYC may function as an oncogene and OCT4, KLF4, NANOG and SOX2 as tumor suppressors. PMID- 21982274 TI - Low-dose pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer's disease. AB - Recent studies have implicated resveratrol and pterostilbene, a resveratrol derivative, in the protection against age-related diseases including Alzheimer's disease (AD). However, the mechanism for the favorable effects of resveratrol in the brain remains unclear and information about direct cross-comparisons between these analogs is rare. As such, the purpose of this study was to compare the effectiveness of diet-achievable supplementation of resveratrol to that of pterostilbene at improving functional deficits and AD pathology in the SAMP8 mouse, a model of accelerated aging that is increasingly being validated as a model of sporadic and age-related AD. Furthermore we sought to determine the mechanism of action responsible for functional improvements observed by studying cellular stress, inflammation, and pathology markers known to be altered in AD. Two months of pterostilbene diet but not resveratrol significantly improved radial arm water maze function in SAMP8 compared with control-fed animals. Neither resveratrol nor pterostilbene increased sirtuin 1 (SIRT1) expression or downstream markers of sirtuin 1 activation. Importantly, markers of cellular stress, inflammation, and AD pathology were positively modulated by pterostilbene but not resveratrol and were associated with upregulation of peroxisome proliferator-activated receptor (PPAR) alpha expression. Taken together our findings indicate that at equivalent and diet-achievable doses pterostilbene is a more potent modulator of cognition and cellular stress than resveratrol, likely driven by increased peroxisome proliferator-activated receptor alpha expression and increased lipophilicity due to substitution of hydroxy with methoxy group in pterostilbene. PMID- 21982275 TI - Prosthesis-patient mismatch in the transcatheter aortic valve replacement era. PMID- 21982276 TI - Hemodynamic and clinical impact of prosthesis-patient mismatch after transcatheter aortic valve implantation. AB - OBJECTIVES: This study examined the mid-term hemodynamic and clinical impact of prosthesis-patient mismatch (PPM) in patients undergoing transcatheter aortic valve implantation (TAVI) with balloon-expandable valves. BACKGROUND: PPM can be observed after aortic valve surgery. However, little is known about the incidence of PPM in patients undergoing TAVI. METHODS: Echocardiography and clinical assessment were performed in 165 patients at baseline, before hospital discharge, and at 6 months after TAVI. PPM was defined as an indexed effective orifice area <=0.85 cm(2)/m(2). RESULTS: Thirty patients (18.2%) showed PPM before hospital discharge. At baseline, patients with PPM had a larger body surface area (1.84 +/ 0.18 m(2) vs. 1.73 +/- 0.18 m(2), p = 0.003) and a greater severity of aortic stenosis (indexed valve area 0.35 +/- 0.09 cm(2)/m(2) vs. 0.40 +/- 0.10 cm(2)/m(2), p = 0.005) than patients without PPM. Patients with PPM demonstrated a slower and smaller reduction in mean transaortic gradient, limited left ventricular (LV) mass regression, and left atrial volume reduction over 6 months compared with patients without PPM. LV filling pressure, measured by E/e', tended to remain elevated in patients with PPM. Importantly, a higher proportion of patients with PPM did not improve in New York Heart Association functional class compared with patients without PPM (36.7% vs. 1.5%, p < 0.001), although major adverse valve-related and cardiovascular events did not differ between the 2 groups. CONCLUSIONS: PPM may be observed after TAVI and when present may be accompanied by less favorable changes in transvalvular hemodynamics, limited LV mass regression, persistent elevated LV filling pressure, and less improvement in clinical functional status. PMID- 21982278 TI - Two stage fluid bed-plasma gasification process for solid waste valorisation: technical review and preliminary thermodynamic modelling of sulphur emissions. AB - Gasification of solid waste for energy has significant potential given an abundant feed supply and strong policy drivers. Nonetheless, significant ambiguities in the knowledge base are apparent. Consequently this study investigates sulphur mechanisms within a novel two stage fluid bed-plasma gasification process. This paper includes a detailed review of gasification and plasma fundamentals in relation to the specific process, along with insight on MSW based feedstock properties and sulphur pollutant therein. As a first step to understanding sulphur partitioning and speciation within the process, thermodynamic modelling of the fluid bed stage has been performed. Preliminary findings, supported by plant experience, indicate the prominence of solid phase sulphur species (as opposed to H(2)S) - Na and K based species in particular. Work is underway to further investigate and validate this. PMID- 21982277 TI - Classification of microarrays; synergistic effects between normalization, gene selection and machine learning. AB - BACKGROUND: Machine learning is a powerful approach for describing and predicting classes in microarray data. Although several comparative studies have investigated the relative performance of various machine learning methods, these often do not account for the fact that performance (e.g. error rate) is a result of a series of analysis steps of which the most important are data normalization, gene selection and machine learning. RESULTS: In this study, we used seven previously published cancer-related microarray data sets to compare the effects on classification performance of five normalization methods, three gene selection methods with 21 different numbers of selected genes and eight machine learning methods. Performance in term of error rate was rigorously estimated by repeatedly employing a double cross validation approach. Since performance varies greatly between data sets, we devised an analysis method that first compares methods within individual data sets and then visualizes the comparisons across data sets. We discovered both well performing individual methods and synergies between different methods. CONCLUSION: Support Vector Machines with a radial basis kernel, linear kernel or polynomial kernel of degree 2 all performed consistently well across data sets. We show that there is a synergistic relationship between these methods and gene selection based on the T-test and the selection of a relatively high number of genes. Also, we find that these methods benefit significantly from using normalized data, although it is hard to draw general conclusions about the relative performance of different normalization procedures. PMID- 21982279 TI - Composting in small laboratory pilots: performance and reproducibility. AB - Small-scale reactors (<10 l) have been employed in composting research, but few attempts have assessed the performance of composting considering the transformations of organic matter. Moreover, composting at small scales is often performed by imposing a fixed temperature, thus creating artificial conditions, and the reproducibility of composting has rarely been reported. The objectives of this study are to design an innovative small-scale composting device safeguarding self-heating to drive the composting process and to assess the performance and reproducibility of composting in small-scale pilots. The experimental setup included six 4-l reactors used for composting a mixture of sewage sludge and green wastes. The performance of the process was assessed by monitoring the temperature, O(2) consumption and CO(2) emissions, and characterising the biochemical evolution of organic matter. A good reproducibility was found for the six replicates with coefficients of variation for all parameters generally lower than 19%. An intense self-heating ensured the existence of a spontaneous thermophilic phase in all reactors. The average loss of total organic matter (TOM) was 46% of the initial content. Compared to the initial mixture, the hot water soluble fraction decreased by 62%, the hemicellulose-like fraction by 68%, the cellulose-like fraction by 50% and the lignin-like fractions by 12% in the final compost. The TOM losses, compost stabilisation and evolution of the biochemical fractions were similar to observed in large reactors or on-site experiments, excluding the lignin degradation, which was less important than in full-scale systems. The reproducibility of the process and the quality of the final compost make it possible to propose the use of this experimental device for research requiring a mass reduction of the initial composted waste mixtures. PMID- 21982280 TI - Quantification of uncertainty in modelled partitioning and removal of heavy metals (Cu, Zn) in a stormwater retention pond and a biofilter. AB - Strategies for reduction of micropollutant (MP) discharges from stormwater drainage systems require accurate estimation of the potential MP removal in stormwater treatment systems. However, the high uncertainty commonly affecting stormwater runoff quality modelling also influences stormwater treatment models. This study identified the major sources of uncertainty when estimating the removal of copper and zinc in a retention pond and a biofilter by using a conceptual dynamic model which estimates MP partitioning between the dissolved and particulate phases as well as environmental fate based on substance-inherent properties. The two systems differ in their main removal processes (settling and filtration/sorption, respectively) and in the time resolution of the available measurements (composite samples and pollutographs). The most sensitive model factors, identified by using Global Sensitivity Analysis (GSA), were related to the physical characteristics of the simulated systems (flow and water losses) and to the fate processes related to Total Suspended Solids (TSS). The model prediction bounds were estimated by using the Generalized Likelihood Uncertainty Estimation (GLUE) technique. Composite samples and pollutographs produced similar prediction bounds for the pond and the biofilter, suggesting a limited influence of the temporal resolution of samples on the model prediction bounds. GLUE highlighted model structural uncertainty when modelling the biofilter, due to disregard of plant-driven evapotranspiration, underestimation of sorption and neglect of oversaturation with respect to minerals/salts. The results of this study however illustrate the potential for the application of conceptual dynamic fate models base on substance-inherent properties, in combination with available datasets and statistical methods, to estimate the MP removal in different stormwater treatment systems and compare with environmental quality standards targeting the dissolved MP fraction. PMID- 21982281 TI - Development of biomass in a drinking water granular active carbon (GAC) filter. AB - Indigenous bacteria are essential for the performance of drinking water biofilters, yet this biological component remains poorly characterized. In the present study we followed biofilm formation and development in a granular activated carbon (GAC) filter on pilot-scale during the first six months of operation. GAC particles were sampled from four different depths (10, 45, 80 and 115 cm) and attached biomass was measured with adenosine tri-phosphate (ATP) analysis. The attached biomass accumulated rapidly on the GAC particles throughout all levels in the filter during the first 90 days of operation and maintained a steady state afterward. Vertical gradients of biomass density and growth rates were observed during start-up and also in steady state. During steady state, biomass concentrations ranged between 0.8-1.83 x 10(-6) g ATP/g GAC in the filter, and 22% of the influent dissolved organic carbon (DOC) was removed. Concomitant biomass production was about 1.8 * 10(12) cells/m(2)h, which represents a yield of 1.26 * 10(6) cells/MUg. The bacteria assimilated only about 3% of the removed carbon as biomass. At one point during the operational period, a natural 5-fold increase in the influent phytoplankton concentration occurred. As a result, influent assimilable organic carbon concentrations increased and suspended bacteria in the filter effluent increased 3-fold as the direct consequence of increased growth in the biofilter. This study shows that the combination of different analytical methods allows detailed quantification of the microbiological activity in drinking water biofilters. PMID- 21982282 TI - Hemoglobin A1c as a tool for the diagnosis of type 2 diabetes in 208 premenopausal women with polycystic ovary syndrome. AB - OBJECTIVE: To study hemoglobin A1c (HbA1c) as a tool for diagnosing diabetes and to study HbA1c as a cardiovascular risk marker in patients with polycystic ovary syndrome (PCOS). DESIGN: Retrospective observational study. SETTING: Academic tertiary-care medical center. PATIENT(S): Two hundred eight premenopausal women with PCOS. INTERVENTION(S): Patients underwent clinical evaluation (Ferriman Gallwey score, body mass index, waist, blood pressure), hormone analyses (T, sex hormone-binding globulin, fasting lipids, insulin, glucose, HbA1c), transvaginal ultrasound, and 2-hour oral glucose tolerance tests (OGTT) measuring capillary blood glucose (BG) at 0 (BG 0) and 120 (BG 120) minutes, insulin, and C-peptide. MAIN OUTCOME MEASURE(S): Results of OGTT, HbA1c values. RESULT(S): Twenty patients were diagnosed with type 2 diabetes during OGTT. The sensitivity and specificity of HbA1c >=6.5% for the diagnosis of diabetes were 35% and 99%, respectively, compared with the diagnosis established by OGTT. Hemoglobin A1c showed closer correlation with waist, body mass index, and lipid profile than BG 120, suggesting that HbA1c could be a cardiovascular risk marker. CONCLUSION(S): The clinical utility of HbA1c for diagnosing impaired glucose tolerance and type 2 diabetes in PCOS in daily practice is low. Long-term prospective studies are needed to determine whether HbA1c is superior to glucose levels as a cardiovascular risk marker in patients with PCOS. PMID- 21982283 TI - Prediction of human blastocyst development from morulas with delayed and/or incomplete compaction. AB - OBJECTIVE: To determine the influence of delayed compaction and fragmentation on the developmental capacity of morulas. DESIGN: Prospective study. SETTING: University IVF center. PATIENT(S): Intracytoplasmic sperm injection (ICSI) cycles with compact embryos on day 4 or day 5. INTERVENTION(S): The embryos were divided into day 4 (n = 329) and day 5 (n = 256) morulas and graded I, II, or III, according to the percentage of fragmentation (<5%, 5%-20%, or >20%). The embryos were measured using Cronus3 software. MAIN OUTCOME MEASUREMENT(S): Blastocyst development rate, blastocoel expansion rate, and optimal blastocyst rate. In an optimal blastocyst: surface area, trophectoderm cell number, inner cell mass (ICM) surface area, ICM volume and ICM shape. RESULT(S): Day 4 morulas in classes I-III developed into optimal blastocysts in 57.4%, 50%, and 35.6% of the total, respectively, and day 5 morulas in classes I-III in 43.3%, 29.1%, and 13.6% of the total, respectively. A negative association was identified between the amount of morula fragmentation, the blastocyst ICM size, and the number of trophectoderm cells. A delay of 1 day in compaction was associated with a reduced ICM volume. CONCLUSION(S): The measurement of compaction timing and cytoplasmic loss in morulas assists in predicting their ability to develop into optimal blastocysts. PMID- 21982284 TI - Effect of postovulatory oocyte aging on DNA methylation imprinting acquisition in offspring oocytes. AB - OBJECTIVE: To investigate whether postovulatory aging of oocytes in the mother affects DNA methylation acquisition of imprinted genes in oocytes from the offspring. DESIGN: Randomized research experimental study. SETTING: Academic basic research laboratory. ANIMAL(S): Mice. INTERVENTION(S): Fresh oocytes and aged oocytes from mothers were artificially inseminated, and oocytes were collected from the resultant offspring. MAIN OUTCOME MEASURE(S): Methylation status was evaluated at differentially methylated regions (DMRs) in oocytes of maternally imprinted genes Peg3, Snrpn, and Peg1 and paternally imprinted gene H19. RESULT(S): Our results showed that methylation patterns at DMRs of Peg3, Snrpn, Peg1, and H19 in oocytes from aged-oocyte offspring were mainly normal, with only a small number of oocytes showing aberrant methylation in the DMR of Peg3. CONCLUSION(S): Postovulatory oocyte aging causes a decline in reproductive outcomes but does not evidently lead to defects in DNA methylation imprinting acquisition in the oocytes from viable offspring. PMID- 21982285 TI - Neonatal exposure to single doses of estradiol or testosterone programs ovarian follicular development-modified hypothalamic neurotransmitters and causes polycystic ovary during adulthood in the rat. AB - OBJECTIVE: To investigate the hormones participating in early follicular development and hypothalamic neurotransmitters in rats during adulthood. DESIGN: Experimental basic study. SETTING: University animal laboratory. ANIMAL(S): Twenty-three neonatal rats injected with single subcutaneous injection of estradiol valerate (EV), testosterone propionate (TP), or dihydrotestosterone (DHT) and killed by decapitation at 60 days of age. INTERVENTION(S): Measurements of neurotransmitter in ventromedial hypothalamus-arcuate nucleus (VMH-AN) and ovarian morphometry in the adult rat. MAIN OUTCOME MEASURE(S): Noradrenaline (NA), dopamine (DA), serotonin (5-HT), glutamic acid (Glu), and gamma aminobutyric acid (GABA) content by high performance liquid chromatography medial basal hypothalamus and ovarian morphology. RESULT(S): EV exposure increased 5-HT, DA, NA, and Glu and decreased GABA levels in the VMH-AN. Exposure to TP increased Glu and decreased 5-HT in the VMH-AN. Neonatal EV and TP decreased the number of primordial follicles but EV increased the atresia of antral follicles and TP decreased it. Neonatal exposure to DHT did not cause morphologic changes in the adult ovary. CONCLUSION(S): Neonatal exposure to EV activated the reproductive hypothalamus and permanently modified ovarian follicular development. TP exposure had some similar effects as EV at the hypothalamus, and it modified ovarian development mimicking the effects of EV. This last effect could be through TP conversion to estradiol because DHT, a nonaromatizable androgen, did not modify follicular development. PMID- 21982287 TI - Gestational sac aspiration and instillation for treatment of early ectopic pregnancy. PMID- 21982288 TI - Changes in marital congruence and quality of life across the transition to parenthood in couples who conceived spontaneously or with assisted reproductive technologies. AB - OBJECTIVE: To investigate the relationship between changes in marital congruence (ie, level of agreement between partners about their relationship) and quality of life across the transition to parenthood in couples who conceived spontaneously and with assisted reproduction technology (ART). DESIGN: Prospective longitudinal cohort design using multilevel modeling. SETTING: Portuguese large public university-based hospital. PATIENT(S): Pregnant couples who conceived spontaneously and with ART. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): ENRICH Marital Inventory and the World Health Organization Brief Quality of Life Instrument. RESULT(S): For all couples, an increase in satisfaction with the marital relationship was associated with increases in all quality of life domains. For couples who conceived with ART only, a decrease from pregnancy to the postpartum period in congruence about the existence of conflicts in their relationship was associated with a decrease in psychologic quality of life. CONCLUSION(S): Couples who conceive with ART are usually satisfied with their marital relationship, but they may still disagree in their perceptions of this relationship, which may negatively impact their well-being. These results reinforce the role of couple-based interventions to prevent intracouple disagreement across the transition to parenthood, especially when conception is achieved with ART. PMID- 21982289 TI - Complete gonadal dysgenesis in clinical practice: the 46,XY karyotype accounts for more than one third of cases. AB - OBJECTIVE: To determine the frequency of XY karyotypes among females with complete gonadal dysgenesis (CGD) and to investigate the frequency of both gonadal tumors and SRY mutations. DESIGN: Retrospective study based on data from all patients with CGD seen in our service from 1989 to 2010. SETTING: Clinic for disorders of sex development, University Hospital, State University of Campinas. PATIENT(S): Thirty-two patients with hypergonadotropic hypogonadism, streak gonads, internal and external female genitalia, and normal karyotype (46,XX or 46,XY); 31 were index cases and 29 did not have a previously determined karyotype. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULT(S): The percentage of XY karyotypes among patients with CGD was 34.5% (10/29). Mean age at diagnosis among XY and XX patients was 17.4 years and 19.9 years, respectively. Gonadal tumors were found in 4 of 9 XY girls, and 7 of 10 had SRY gene mutations. CONCLUSION(S): The previously unreported finding of an elevated frequency of 46,XY karyotype among patients with CGD and the high risk of gonadal neoplasia in such cases indicate that this diagnosis must be kept in mind by clinicians and strengthen the importance of karyotype analysis in females with primary hypogonadism. In addition, the frequency of SRY mutations in XY CGD might be higher than previously considered. PMID- 21982290 TI - Association of menopause and hormone replacement therapy with large artery remodeling. AB - OBJECTIVE: To evaluate the remodeling of large arteries according to age at menopause, duration of menopause, and use of hormone therapy (HT). DESIGN: A cross-sectional study consisting of baseline measurements of a multicentric randomized trial were used to evaluate arterial parameters. SETTING: The study was conducted in France, Belgium, and the Netherlands in academic hospitals and private clinics. PATIENT(S): Postmenopausal women (n = 538) with mild hypercholesterolemia. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Common carotid artery intima-media thickness (CCA-IMT), central pulse pressure, and aortic stiffness (carotid-femoral pulse wave velocity) were measured and centrally controlled for quality. Multivariate regression analysis was used to assess the possible covariates associated with arterial parameters. RESULT(S): Women were 58 +/- 6 (mean +/- SD) years of age with an age of 50 +/- 5 at menopause and a mean duration of menopause of 8 +/- 7 years. Lower age at menopause, time since menopause, and absence of HT use were independently associated with worsening of the arterial parameters. After multivariate analysis, HT was associated with a lower CCA-IMT (-40 MUm [range -64 to -1]), whereas lower age at menopause and menopause duration were respectively associated with a CCA-IMT increase (25 MUm/5 y and 27 MUm/5 y). Similarly, values of central pulse pressure and pulse wave velocity were lower in HT users (-3.1 mm Hg [-5.1 to -0.9] and -0.31 m/s [-0.63 to -0.02], respectively) but worsened with age at menopause and menopause duration. CONCLUSION(S): The age at menopause, the time since menopause, and the use of HT are independently associated with the thickening and stiffening of the large arteries. CLINICAL TRIAL REGISTRATION NUMBER: NCT00163163. PMID- 21982291 TI - Live birth after allografting of ovarian cortex between monozygotic twins with Turner syndrome (45,XO/46,XX mosaicism) and discordant ovarian function. AB - OBJECTIVE: To report the restoration of ovarian function in a woman with Turner syndrome by allografting ovarian cortex from her monozygotic twin. DESIGN: Case report. SETTING: Gynecology research unit in a university hospital. PATIENT(S): A 37-year-old woman with Turner syndrome who had suffered premature ovarian failure (POF) at the age of 15. INTERVENTION(S): In this woman, we performed ovarian cortex transplantation. The donor was her monozygotic twin who had not experienced POF and who had had two normal deliveries. MAIN OUTCOME MEASURE(S): Restoration of ovarian activity and pregnancy. RESULT(S): Restoration of ovarian function was achieved 3 months after transplantation. After 7 months of regular cycles, spontaneous pregnancy occurred. The patient delivered a healthy baby girl weighing 2,850 g at 38 weeks of gestation. CONCLUSION(S): Girls with Turner syndrome suffer accelerated loss of ovarian follicles and only 2%-5% experience spontaneous menses with the potential to achieve pregnancy without medical intervention. This manuscript reports the first live birth after allografting between monozygotic twins with 45,XO/46,XX mosaicism and discordant growth pattern and ovarian function. PMID- 21982292 TI - An FRET-based ratiometric chemosensor for in vitro cellular fluorescence analyses of pH. AB - Ratiometric fluorescence sensing is an important technique for precise and quantitative analysis of biological events occurring under complex conditions by simultaneously recording fluorescence intensities at two wavelengths and calculating their ratios. Herein, we design a ratiometric chemosensor for pH that is based on photo-induced electron transfer (PET) and binding-induced modulation of fluorescence resonance energy transfer (FRET) mechanisms. This ratiometric chemosensor was constructed by introduction of a pH-insensitive coumarin fluorophore as an FRET donor into a pH-sensitive amino-naphthalimide derivative as the FRET acceptor. The sensor exhibited clear dual-mission signal changes in blue and green spectral windows upon pH changes. The pH sensor was applied for not only measuring cellular pH, but also for visualizing stimulus-responsive changes of intracellular pH values. PMID- 21982293 TI - Silk fibroin derived polypeptide-induced biomineralization of collagen. AB - Silk fibroin (SF) is extensively investigated in osteoregenerative therapy as it combines extraordinary mechanical properties and directs calcium-phosphate formation. However, the role of the peptidic fractions in inducing the protein mineralization has not been previously decoded. In this study, we investigated the mineralization of fibroin-derived polypeptides (FDPs), which were obtained through the chymotryptic separation of the hydrophobic crystalline (Cp) fractions and of the hydrophilic electronegative amorphous (Cs) fractions. When immersed in simulated body fluid (SBF), only Cs fragments demonstrated the formation of carbonated apatite, providing experimental evidence that the mineralization of SF is dictated exclusively by its electronegative amino-acidic sequences. The potential of Cs to conceptually mimic the role of anionic non-collagenous proteins in biomineralization processes was investigated via their incorporation (up to 10% by weight) in bulk osteoid-like dense collagen (DC) gels. Within 6 h in SBF, apatite was formed in DC-Cs hybrid gels, and by day 7, carbonated hydroxylapatite crystals were extensively formed. This accelerated 3-D mineralization resulted in a nine-fold increase in the compressive modulus of the hydrogel. The tailoring of the mineralization and mechanical properties of hydrogels through hybridization with FDPs could potentially have a significant impact on cell delivery and bone regenerative medicine. PMID- 21982294 TI - Contact activation of blood plasma and factor XII by ion-exchange resins. AB - Sepharose ion-exchange particles bearing strong Lewis acid/base functional groups (sulfopropyl, carboxymethyl, quaternary ammonium, dimethyl aminoethyl, and iminodiacetic acid) exhibiting high plasma protein adsorbent capacities are shown to be more efficient activators of blood factor XII in neat-buffer solution than either hydrophilic clean-glass particles or hydrophobic octyl sepharose particles (FXII (activator)->(surface) FXIIa; a.k.a autoactivation, where FXII is the zymogen and FXIIa is a procoagulant protease). In sharp contrast to the clean glass standard of comparison, ion-exchange activators are shown to be inefficient activators of blood plasma coagulation. These contrasting activation properties are proposed to be due to the moderating effect of plasma-protein adsorption on plasma coagulation. Efficient adsorption of blood-plasma proteins unrelated to the coagulation cascade impedes FXII contacts with ion-exchange particles immersed in plasma, reducing autoactivation, and causing sluggish plasma coagulation. By contrast, plasma proteins do not adsorb to hydrophilic clean glass and efficient autoactivation leads directly to efficient activation of plasma coagulation. It is also shown that competitive-protein adsorption can displace FXIIa adsorbed to the surface of ion-exchange resins. As a consequence of highly-efficient autoactivation and FXIIa displacement by plasma proteins, ion exchange particles are slightly more efficient activators of plasma coagulation than hydrophobic octyl sepharose particles that do not bear strong Lewis acid/base surface functionalities but to which plasma proteins adsorb efficiently. Plasma proteins thus play a dual role in moderating contact activation of the plasma coagulation cascade. The principal role is impeding FXII contact with activating surfaces, but this same effect can displace FXIIa from an activating surface into solution where the protease can potentiate subsequent steps of the plasma coagulation cascade. PMID- 21982295 TI - Modulation of osteogenic differentiation in hMSCs cells by submicron topographically-patterned ridges and grooves. AB - Recent studies have shown that nanoscale and submicron topographic cues modulate a menu of fundamental cell behaviors, and the use of topographic cues is an expanding area of study in tissue engineering. We used topographically-patterned substrates containing anisotropically ordered ridges and grooves to investigate the effects of topographic cues on mesenchymal stem cell morphology, proliferation, and osteogenic differentiation. We found that human mesenchymal stem cells cultured on 1400 or 4000 nm pitches showed greater elongation and alignment relative to 400 nm pitch or planar control. Cells cultured on 400 nm pitch demonstrated significant increases in RUNX2 and BGLAP expression relative to cells cultured on 1400 or 4000 nm pitch or planar control. Four-hundred nanometer pitch enhanced extracellular calcium deposition. Cells cultured in osteoinductive medium revealed combinatory effects of topography and chemical cues on 400 nm pitch as well as up-regulation of expression of ID1, a target of the BMP pathway. Our data demonstrate that a specific size scale of topographic cue promotes osteogenic differentiation with or without osteogenic agents. These data demonstrate that the integration of topographic cues may be useful for the fabrication of orthopedic implants. PMID- 21982296 TI - Surface modification of pancreatic islets using heparin-DOPA conjugate and anti CD154 mAb for the prolonged survival of intrahepatic transplanted islets in a xenograft model. AB - This study proposes a combination method of using 3,4-dihydorxy-l-phenylalanine (DOPA) conjugated heparin (heparin-DOPA) and a low dose of anti-CD154 monoclonal antibody (MR-1) treatment to improve the survival time of intrahepatic islet xenograft. To inhibit instant blood mediated inflammatory reactions, heparin-DOPA was directly grafted to the pancreatic islet surface. The surface coverage of heparin-DOPA, the viability and functionality of heparin-DOPA grafted islets were evaluated. In addition, the combined effect of grafted heparin-DOPA and a low dose of MR-1 (a T-cell targeting immunosuppressive drug) on the survival of islet was evaluated in a xenograft model. Both unmodified islets and heparin-DOPA grafted islets were completely rejected within 2 weeks after intraportal transplantation. However, when 0.1 mg/mouse of MR-1 was administered (at day 0, 2, 4, 6 of transplantation) to 11 mice that had heparin-DOPA grafted islets transplanted to, seven out of the recipients maintained normoglycemia over 60 days. Therefore, we propose that a developed combinatory immunoprotection protocol of surface modification of pancreatic islets using heparin-DOPA with a low dose of MR-1 can be effective in prolonging the survival rate of transplanted islets in a xenograft model. PMID- 21982297 TI - Topographic control of the growth and function of cardiomyoblast H9c2 cells using nanodot arrays. AB - Cardiovascular stents require optimised control for the enhancement or inhibition epithelial and smooth muscle cell growth in close contact with the implant. Here we propose that the surface topology in contact with the living cells could be designed to control and optimise the growth and function of such cells. The cardiomyoblast H9c2 was cultured on nanodot arrays with dot diameters ranging between 10 and 200 nm. On the 50-nm nanodot arrays H9c2 showed maximum attachment and proliferation with largest cell area and extended lamellipodia. In contrast, 53.7% and 72.6% reductions of growth were observed on the 100- and 200-nm nanodot arrays after 3 days. Immunostaining indicated that nanodots smaller than 50-nm induced cell adhesion and cytoskeleton organization. Expression of genes associated with fibrosis and hypertrophy was up-regulated in cells grown on 100 nm nanodots. Western blot data showed high levels of expression for vinculin and plasminogen activator inhibitor-1 for cells cultured on 50-nm nanodots. Nanotopography controls cell adhesion, morphology and proliferation. By adjusting the diameter of the nanodots, we could modulate the growth and expression of function-related genes and proteins of H9c2 cardiomyoblasts. The current study provides insights for improved design of artificial implants and parameters that affect biocompatibility. PMID- 21982298 TI - Continuous theta-burst stimulation of the primary motor cortex in essential tremor. AB - OBJECTIVE: We investigated whether essential tremor (ET) can be altered by suppressing the corticospinal excitability in the primary motor cortex (M1) with transcranial magnetic stimulation. METHODS: 10 Patients with ET and 10 healthy controls underwent transcranial continuous theta-burst stimulation (cTBS) of the left primary motor hand area at 80% (real cTBS) and 30% (control cTBS) of active motor threshold in two separate sessions at least one week apart. Postural tremor was rated clinically and measured accelerometrically before and after cTBS. Corticospinal excitability was assessed by recording the motor evoked potentials (MEP) from the first dorsal interosseous muscle. RESULTS: Real cTBS but not control cTBS reduced the tremor total power assessed with accelerometry. This beneficial effect was subclinical as there were no significant changes in clinical tremor rating after real cTBS. Relative to control cTBS, real cTBS reduced corticospinal excitability in the stimulated primary motor cortex only in healthy controls but not in ET patients. CONCLUSION: Real cTBS has a beneficial effect on ET. Since cTBS did not induce a parallel reduction in corticospinal excitability, this effect was not mediated by a suppression of the corticospinal motor output. SIGNIFICANCE: "Inhibitory" cTBS of M1 leads to a consistent but subclinical reduction in tremor amplitude. PMID- 21982299 TI - Repetitive transcranial magnetic stimulation as a treatment for essential tremor? PMID- 21982300 TI - Open Babel: An open chemical toolbox. AB - BACKGROUND: A frequent problem in computational modeling is the interconversion of chemical structures between different formats. While standard interchange formats exist (for example, Chemical Markup Language) and de facto standards have arisen (for example, SMILES format), the need to interconvert formats is a continuing problem due to the multitude of different application areas for chemistry data, differences in the data stored by different formats (0D versus 3D, for example), and competition between software along with a lack of vendor neutral formats. RESULTS: We discuss, for the first time, Open Babel, an open source chemical toolbox that speaks the many languages of chemical data. Open Babel version 2.3 interconverts over 110 formats. The need to represent such a wide variety of chemical and molecular data requires a library that implements a wide range of cheminformatics algorithms, from partial charge assignment and aromaticity detection, to bond order perception and canonicalization. We detail the implementation of Open Babel, describe key advances in the 2.3 release, and outline a variety of uses both in terms of software products and scientific research, including applications far beyond simple format interconversion. CONCLUSIONS: Open Babel presents a solution to the proliferation of multiple chemical file formats. In addition, it provides a variety of useful utilities from conformer searching and 2D depiction, to filtering, batch conversion, and substructure and similarity searching. For developers, it can be used as a programming library to handle chemical data in areas such as organic chemistry, drug design, materials science, and computational chemistry. It is freely available under an open-source license from http://openbabel.org. PMID- 21982301 TI - Prehypertension in adolescents: how high is the risk for hypertension? PMID- 21982302 TI - Heart rate characteristic monitoring-HeRO or villain? PMID- 21982303 TI - Intravenous fat emulsions reduction for patients with parenteral nutrition associated liver disease. AB - OBJECTIVE: To test the hypothesis that implementation of a marked reduction in intravenous fat will result in reversal of parenteral nutrition-associated liver disease (PNALD) in infants. STUDY DESIGN: Prospective study of intravenous fat emulsion reduction in parenteral nutrition to 1 g/kg/d 2 times per week in neonates diagnosed with PNALD. Primary outcome measure was total bilirubin levels compared with gestational age, birth weight, and diagnosis-matched historical controls receiving 3 g/kg/d of intravenous lipids. RESULTS: Intravenous fat emulsion reduction resulted in a significant decline in total bilirubin levels compared with controls. Comparison of growth in the 2 groups was similar. Mild essential fatty acid deficiency was detected in 8 of 31 infants and was reversed with additional days of lipid infusion. No significant adverse events were noted. CONCLUSIONS: An association between intravenous lipid emulsion administration and the development of PNALD seems probable. Use of intravenous fat emulsion reduction is a potential approach to reverse PNALD in young infants. Frequent monitoring of essential fatty acid deficiency is needed with the use of this regimen. PMID- 21982304 TI - Development of cystic periventricular leukomalacia in newborn infants after rotavirus infection. AB - We describe 5 preterm and 3 term infants who presented with seizures during rotavirus infection within 6 weeks after birth. Six of these infants developed late-onset cystic periventricular leukomalacia. Four of the preterm infants had neurodevelopmental delay, and 4 (near) term infants had normal early outcome. PMID- 21982305 TI - A novel method for spectrophotometric determination of pregabalin in pure form and in capsules. AB - BACKGROUND: Pregabalin, a gamma-amino-n-butyric acid derivative, is an antiepileptic drug not yet official in any pharmacopeia and development of analytical procedures for this drug in bulk/formulation forms is a necessity. We herein, report a new, simple, extraction free, cost effective, sensitive and reproducible spectrophotometric method for the determination of the pregabalin. RESULTS: Pregabalin, as a primary amine was reacted with ninhydrin in phosphate buffer pH 7.4 to form blue violet colored chromogen which could be measured spectrophotometrically at lambdamax 402.6 nm. The method was validated with respect to linearity, accuracy, precision and robustness. The method showed linearity in a wide concentration range of 50-1000 MUg mL-1 with good correlation coefficient (0.992). The limits of assays detection was found to be 6.0 MUg mL-1 and quantitation limit was 20.0 MUg mL-1. The suggested method was applied to the determination of the drug in capsules. No interference could be observed from the additives in the capsules. The percentage recovery was found to be 100.43 +/- 1.24. CONCLUSION: The developed method was successfully validated and applied to the determination of pregabalin in bulk and pharmaceutical formulations without any interference from common excipients. Hence, this method can be potentially useful for routine laboratory analysis of pregabalin. PMID- 21982306 TI - Maternal obesity support services: a qualitative study of the perspectives of women and midwives. AB - BACKGROUND: Twenty percent of pregnant women in the UK are obese (BMI >= 30 kg/m2), reflecting the growing public health challenge of obesity in the 21st century. Obesity increases the risk of adverse outcomes during pregnancy and birth and has significant cost implications for maternity services. Gestational weight management strategies are a high priority; however the evidence for effective, feasible and acceptable weight control interventions is limited and inconclusive. This qualitative study explored the experiences and perceptions of pregnant women and midwives regarding existing support for weight management in pregnancy and their ideas for service development. METHODS: A purposive sample of 6 women and 7 midwives from Doncaster, UK, participated in two separate focus groups. Transcripts were analysed thematically. RESULTS: Two overarching themes were identified, 'Explanations for obesity and weight management' and 'Best care for pregnant women'. 'Explanations' included a lack of knowledge about weight, diet and exercise during pregnancy; self-talk messages which excused overeating; difficulties maintaining motivation for a healthy lifestyle; the importance of social support; stigmatisation; and sensitivity surrounding communication about obesity between midwives and their clients. 'Best care' suggested that weight management required care which was consistent and continuous, supportive and non judgemental, and which created opportunities for interaction and mutual support between obese pregnant women. CONCLUSIONS: Women need unambiguous advice regarding healthy lifestyles, diet and exercise in pregnancy to address a lack of knowledge and a tendency towards unhelpful self-talk messages. Midwives expressed difficulties in communicating with their clients about their weight, given awareness that obesity is a sensitive and potentially stigmatising issue. This indicates more could be done to educate and support them in their work with obese pregnant women. Motivation and social support were strong explanatory themes for obesity and weight management, suggesting that interventions should focus on motivational strategies and social support facilitation. PMID- 21982307 TI - How learning style affects evidence-based medicine: a survey study. AB - BACKGROUND: Learning styles determine how people manage new information. Evidence based medicine (EBM) involves the management of information in clinical practice. As a consequence, the way in which a person uses EBM can be related to his or her learning style. In order to tailor EBM education to the individual learner, this study aims to determine whether there is a relationship between an individual's learning style and EBM competence (knowledge/skills, attitude, behaviour). METHODS: In 2008, we conducted a survey among 140 novice GP trainees in order to assess their EBM competence and learning styles (Accommodator, Diverger, Assimilator, Converger, or mixed learning style). RESULTS: The trainees' EBM knowledge/skills (scale 0-15; mean 6.8; 95%CI 6.4-7.2) were adequate and their attitudes towards EBM (scale 0-100; mean 63; 95%CI 61.3-64.3) were positive. We found no relationship between their knowledge/skills or attitudes and their learning styles (p = 0.21; p = 0.19). Of the trainees, 40% used guidelines to answer clinical questions and 55% agreed that the use of guidelines is the most appropriate way of applying EBM in general practice. Trainees preferred using evidence from summaries to using evidence from single studies. There were no differences in medical decision-making or in EBM use (p = 0.59) for the various learning styles. However, we did find a link between having an Accommodating or Converging learning style and making greater use of intuition. Moreover, trainees with different learning styles expressed different ideas about the optimal use of EBM in primary care. CONCLUSIONS: We found that EBM knowledge/skills and EBM attitudes did not differ with respect to the learning styles of GP trainees. However, we did find differences relating to the use of intuition and the trainees' ideas regarding the use of evidence in decision-making. PMID- 21982308 TI - The year in clinical cardiac electrophysiology. PMID- 21982309 TI - Microembolization during carotid artery stenting in patients with high-risk, lipid-rich plaque. A randomized trial of proximal versus distal cerebral protection. AB - OBJECTIVES: The goal of this study was to compare the rate of cerebral microembolization during carotid artery stenting (CAS) with proximal versus distal cerebral protection in patients with high-risk, lipid-rich plaque. BACKGROUND: Cerebral protection with filters partially reduces the cerebral embolization rate during CAS. Proximal protection has been introduced to further decrease embolization risk. METHODS: Fifty-three consecutive patients with carotid artery stenosis and lipid-rich plaque were randomized to undergo CAS with proximal protection (MO.MA system, n = 26) or distal protection with a filter (FilterWire EZ, n = 27). Microembolic signals (MES) were assessed by using transcranial Doppler during: 1) lesion wiring; 2) pre-dilation; 3) stent crossing; 4) stent deployment; 5) stent dilation; and 6) device retrieval/deflation. Diffusion-weighted magnetic resonance imaging was conducted before CAS, after 48 h, and after 30 days. RESULTS: Patients in the MO.MA group had higher percentage diameter stenosis (89 +/- 6% vs. 86 +/- 5%, p = 0.027) and rate of ulcerated plaque (35% vs. 7.4%; p = 0.019). Compared with use of the FilterWire EZ, MO.MA significantly reduced mean MES counts (p < 0.0001) during lesion crossing (mean 18 [interquartile range (IQR): 11 to 30] vs. 2 [IQR: 0 to 4]), stent crossing (23 [IQR: 11 to 34] vs. 0 [IQR: 0 to 1]), stent deployment (30 [IQR: 9 to 35] vs. 0 [IQR: 0 to 1]), stent dilation (16 [IQR: 8 to 30] vs. 0 [IQR: 0 to 1]), and total MES (93 [IQR: 59 to 136] vs. 16 [IQR: 7 to 36]). The number of patients with MES was higher with the FilterWire EZ versus MO.MA in phases 3 to 5 (100% vs. 27%; p < 0.0001). By multivariate analysis, the type of brain protection was the only independent predictor of total MES number. No significant difference was found in the number of patients with new post-CAS embolic lesion in the MO.MA group (2 of 14, 14%) as compared with the FilterWire EZ group (9 of 21, 42.8%). CONCLUSIONS: In patients with high-risk, lipid-rich plaque undergoing CAS, MO.MA led to significantly lower microembolization as assessed by using MES counts. PMID- 21982311 TI - How much statin intervention is enough? PMID- 21982310 TI - Benefit of early statin therapy in patients with acute myocardial infarction who have extremely low low-density lipoprotein cholesterol. AB - OBJECTIVES: We investigated whether statin therapy could be beneficial in patients with acute myocardial infarction (AMI) who have baseline low-density lipoprotein cholesterol (LDL-C) levels below 70 mg/dl. BACKGROUND: Intensive lipid-lowering therapy with a target LDL-C value <70 mg/dl is recommended in patients with very high cardiovascular risk. However, whether to use statin therapy in patients with baseline LDL-C levels below 70 mg/dl is controversial. METHODS: We analyzed 1,054 patients with AMI who had baseline LDL-C levels below 70 mg/dl and survived at discharge from the Korean Acute MI Registry between November 2005 and December 2007. They were divided into 2 groups according to the prescribing of statins at discharge (statin group n = 607; nonstatin group n = 447). The primary endpoint was the composite of 1-year major adverse cardiac events, including death, recurrent MI, target vessel revascularization, and coronary artery bypass grafting. RESULTS: Statin therapy significantly reduced the risk of the composite primary endpoint (adjusted hazard ratio [HR]: 0.56; 95% confidence interval [CI]: 0.34 to 0.89; p = 0.015). Statin therapy reduced the risk of cardiac death (HR: 0.47; 95% CI: 0.23 to 0.93; p = 0.031) and coronary revascularization (HR: 0.45, 95% CI: 0.24 to 0.85; p = 0.013). However, there were no differences in the risk of the composite of all-cause death, recurrent MI, and repeated percutaneous coronary intervention rate. CONCLUSIONS: Statin therapy in patients with AMI with LDL-C levels below 70 mg/dl was associated with improved clinical outcome. PMID- 21982312 TI - High serum testosterone is associated with reduced risk of cardiovascular events in elderly men. The MrOS (Osteoporotic Fractures in Men) study in Sweden. AB - OBJECTIVES: We tested the hypothesis that serum total testosterone and sex hormone-binding globulin (SHBG) levels predict cardiovascular (CV) events in community-dwelling elderly men. BACKGROUND: Low serum testosterone is associated with increased adiposity, an adverse metabolic risk profile, and atherosclerosis. However, few prospective studies have demonstrated a protective link between endogenous testosterone and CV events. Polymorphisms in the SHBG gene are associated with risk of type 2 diabetes, but few studies have addressed SHBG as a predictor of CV events. METHODS: We used gas chromatography/mass spectrometry to analyze baseline levels of testosterone in the prospective population-based MrOS (Osteoporotic Fractures in Men) Sweden study (2,416 men, age 69 to 81 years). SHBG was measured by immunoradiometric assay. CV clinical outcomes were obtained from central Swedish registers. RESULTS: During a median 5-year follow-up, 485 CV events occurred. Both total testosterone and SHBG levels were inversely associated with the risk of CV events (trend over quartiles: p = 0.009 and p = 0.012, respectively). Men in the highest quartile of testosterone (>=550 ng/dl) had a lower risk of CV events compared with men in the 3 lower quartiles (hazard ratio: 0.70, 95% confidence interval: 0.56 to 0.88). This association remained after adjustment for traditional CV risk factors and was not materially changed in analyses excluding men with known CV disease at baseline (hazard ratio: 0.71, 95% confidence interval: 0.53 to 0.95). In models that included both testosterone and SHBG, testosterone but not SHBG predicted CV risk. CONCLUSIONS: High serum testosterone predicted a reduced 5-year risk of CV events in elderly men. PMID- 21982313 TI - Cardiac resynchronization therapy reduces left atrial volume and the risk of atrial tachyarrhythmias in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy). AB - OBJECTIVES: We hypothesized that reductions in left atrial volume (LAV) with a cardiac resynchronization therapy-defibrillator (CRT-D) would translate into a subsequent reduction in the risk of atrial tachyarrhythmias (AT). BACKGROUND: There is limited information regarding the effect of CRT-D on the risk of AT. METHODS: Percent reduction in LAV at 1 year following CRT-D implantation (pre specified as low [lowest quartile: <20% reduction in LAV] and high [>=20% reduction in LAV] response to CRT-D) were related to the risk of subsequent AT (comprising atrial fibrillation, atrial flutter, atrial tachycardia, and supraventricular tachyarrhythmias) among patients enrolled in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy). RESULTS: The cumulative probability of AT 2.5 years after assessment of echocardiographic response was lowest among high LAV responders to CRT-D (3%) and significantly higher among both low LAV responders to CRT-D (9%) and implantable cardioverter-defibrillator-only patients (7%; p = 0.03 for the difference among the 3 groups). Consistently, multivariate analysis showed that high LAV responders to CRT-D experienced a significant 53% (p = 0.01) reduction in the risk of subsequent AT as compared with implantable cardioverter defibrillator-only patients, whereas low LAV responders did not derive a significant risk reduction with CRT-D therapy (hazard ratio [HR]: 1.05 [95% confidence interval (CI): 0.54 to 2.00]; p = 0.89). Patients who developed in trial AT experienced significant increases in the risk for both the combined endpoint of heart failure or death (HR: 2.28 [95% CI: 1.45 to 3.59]; p < 0.001) and the separate occurrence of all-cause mortality (HR: 1.89 [95% CI: 1.08 to 3.62]; p = 0.01). CONCLUSIONS: In the MADIT-CRT study, favorable reverse remodeling of the left atrium with CRT-D therapy was associated with a significant reduction in risk of subsequent AT. (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy [MADIT CRT]; NCT00180271). PMID- 21982314 TI - Comparative effectiveness and cost-effectiveness of computed tomography screening for coronary artery calcium in asymptomatic individuals. AB - OBJECTIVES: The aim of this study was to assess the (cost-) effectiveness of screening asymptomatic individuals at intermediate risk of coronary heart disease (CHD) for coronary artery calcium with computed tomography (CT). BACKGROUND: Coronary artery calcium on CT improves prediction of CHD. METHODS: A Markov model was developed on the basis of the Rotterdam Study. Four strategies were evaluated: 1) current practice; 2) current prevention guidelines for cardiovascular disease; 3) CT screening for coronary calcium; and 4) statin therapy for all individuals. Asymptomatic individuals at intermediate risk of CHD were simulated over their remaining lifetime. Quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios were calculated. RESULTS: In men, CT screening was more effective and more costly than the other 3 strategies (CT vs. current practice: +0.13 QALY [95% confidence interval (CI): 0.01 to 0.26], +$4,676 [95% CI: $3,126 to $6,339]; CT vs. statin therapy: +0.04 QALY [95% CI: -0.02 to 0.13], +$1,951 [95% CI: $1,170 to $2,754]; and CT vs. current guidelines: +0.02 QALY [95% CI: -0.04 to 0.09], +$44 [95% CI: -$441 to $486]). The incremental cost-effectiveness ratio of CT calcium screening was $48,800/QALY gained. In women, CT screening was more effective and more costly than current practice (+0.13 QALY [95% CI: 0.02 to 0.28], +$4,663 [95% CI: $3,120 to $6,277]) and statin therapy (+0.03 QALY [95% CI: -0.03 to 0.12], +$2,273 [95% CI: $1,475 to $3,109]). However, implementing current guidelines was more effective compared with CT screening (+0.02 QALY [95% CI: -0.03 to 0.07]), only a little more expensive (+$297 [95% CI: -$8 to $633]), and had a lower cost per additional QALY ($33,072/QALY vs. $35,869/QALY). Sensitivity analysis demonstrated robustness of results in women but considerable uncertainty in men. CONCLUSIONS: Screening for coronary artery calcium with CT in individuals at intermediate risk of CHD is probably cost-effective in men but is unlikely to be cost-effective in women. PMID- 21982315 TI - Time for a policy change for coronary artery calcium testing in asymptomatic people? PMID- 21982316 TI - Prospective validation of the prognostic usefulness of B-type natriuretic peptide in asymptomatic patients with chronic severe aortic regurgitation. AB - OBJECTIVES: The purpose of this study was to determine the independent and additive prognostic value of B-type natriuretic peptide (BNP) in patients with severe asymptomatic aortic regurgitation and normal left ventricular function. BACKGROUND: Early surgery could be advisable in selected patients with chronic severe aortic regurgitation, but there are no uniform criteria to identify candidates who could benefit from this strategy. Assessment of BNP has not been studied for this purpose. METHODS: We prospectively evaluated 294 consecutive patients with severe asymptomatic organic aortic regurgitation and left ventricular ejection fraction above 55%. The first 160 consecutive patients served as the derivation cohort and the next 134 patients served as a validation cohort. The combined endpoint was the occurrence of symptoms of congestive heart failure, left ventricular dysfunction, or death at follow-up. RESULTS: The endpoint was reached in 45 patients (28%) of the derivation set and in 35 patients (26%) of the validation cohort. Receiver-operator characteristic curve analysis yielded an optimal cutoff point of 130 pg/ml for BNP that was able to discriminate between patients at higher risk in both cohorts. BNP was the strongest independent predictor by multivariate analysis in the derivation set (odds ratio: 6.9 [95% confidence interval: 2.52 to 17.57], p < 0.0001) and the validation set (odds ratio: 6.7 [95% confidence interval: 2.9 to 16.9], p = 0.0001). CONCLUSIONS: Among patients with severe asymptomatic aortic regurgitation and normal left ventricular function, BNP >=130 pg/ml categorizes a subgroup of patients at higher risk. Because of its incremental prognostic value, we believe BNP assessment should be used in the routine clinical evaluation of these patients. PMID- 21982318 TI - An unusual case of recurrent syncope. PMID- 21982317 TI - Human oxidation-specific antibodies reduce foam cell formation and atherosclerosis progression. AB - OBJECTIVES: We sought to assess the in vivo importance of scavenger receptor (SR) mediated uptake of oxidized low-density lipoprotein (OxLDL) in atherogenesis and to test the efficacy of human antibody IK17-Fab or IK17 single-chain Fv fragment (IK17-scFv), which lacks immunologic properties of intact antibodies other than the ability to inhibit uptake of OxLDL by macrophages, to inhibit atherosclerosis. BACKGROUND: The unregulated uptake of OxLDL by macrophage SR contributes to foam cell formation, but the importance of this pathway in vivo is uncertain. METHODS: Cholesterol-fed low-density lipoprotein receptor knockout (LDLR(-/-)) mice were treated with intraperitoneal infusion of human IK17-Fab (2.5 mg/kg) 3 times per week for 14 weeks. Because anti-human antibodies developed in these mice, LDLR(-/-)/low-density lipoprotein receptor Rag 1 double knockout mice (lacking the ability to make immunoglobulins due to loss of T- and B-cell function) were treated with an adenoviral vector encoding adenovirus expressed (Adv)-IK17-scFv or control adenovirus-enhanced green fluorescent protein vector intravenously every 2 weeks for 16 weeks. RESULTS: In LDLR(-/-) mice, infusion of IK17-Fab was able to sustain IK17 plasma levels for the first 8 weeks, but these diminished afterward due to increasing murine anti-IK17 antibody titers. Despite this, after 14 weeks, a 29% decrease in en face atherosclerosis was noted compared with phosphate-buffered saline-treated mice. In LDLR(-/-)/low density lipoprotein receptor Rag 1 double-knockout mice, sustained levels of plasma IK17-scFv was achieved by Adv-IK17-scFv-mediated hepatic expression, which led to a 46% reduction (p < 0.001) in en face atherosclerosis compared with adenovirus-enhanced green fluorescent protein vector. Importantly, peritoneal macrophages isolated from Adv-IK17-scFv treated mice had decreased lipid accumulation compared with adenovirus-enhanced green fluorescent protein-treated mice. CONCLUSIONS: These data support an important role for SR-mediated uptake of OxLDL in the pathogenesis of atherosclerosis and demonstrate that oxidation specific antibodies reduce the progression of atherosclerosis, suggesting their potential in treating cardiovascular disease in humans. PMID- 21982319 TI - Transcatheter aortic valve implantation in degenerate failing aortic homograft root replacements. PMID- 21982320 TI - Invasive validation of the N-point moving average method. PMID- 21982322 TI - Acute coronary syndrome in 3 dimensions: the culprit exposed. PMID- 21982323 TI - Intramural aortic hematoma definitive diagnosis combining computed tomography and magnetic resonance imaging. PMID- 21982324 TI - The effects of pressure release, phonophoresis of hydrocortisone, and ultrasound on upper trapezius latent myofascial trigger point. AB - OBJECTIVE: To compare the effects of pressure release (PR), phonophoresis of hydrocortisone (PhH) 1%, and ultrasonic therapy (UT) in patients with an upper trapezius latent myofascial trigger point (MTP). DESIGN: Repeated-measure design. SETTING: A pain control medical clinic. PARTICIPANTS: Subjects (N=60; mean+/-SD age, 21.78+/-1.76y) with a diagnosis of upper trapezius MTP participated in this study. Subjects were randomly divided into 4 groups: PR, PhH, UT, and control (15 in each group). All patients had a latent MTP in the upper trapezius muscle. INTERVENTIONS: PR, PhH, UT. MAIN OUTCOME MEASURES: Subjective pain intensity, pain pressure threshold (PPT), and active cervical lateral flexion range of motion were assessed in 6 sessions. RESULTS: All 3 treatment groups showed decreases in pain and PPT and an increase in cervical lateral flexion range of motion (P<.001) compared with the control group. Both PhH and PR techniques showed more significant therapeutic effects than UT (P<.001). CONCLUSIONS: Our results indicate that all 3 treatments used in this study were effective for treating MTP. According to this study, PhH is suggested as a new method effective for the treatment of MTP. PMID- 21982326 TI - Clinical oncology training: the trainees' perspective. PMID- 21982325 TI - A randomized controlled trial to investigate the effects of water-based exercise to improve falls risk and physical function in older adults with lower-extremity osteoarthritis. AB - OBJECTIVE: To investigate the efficacy of a water-based exercise program specifically targeting balance to reduce falls risk and improve measures of balance and physical function in older adults with osteoarthritis (OA). DESIGN: Randomized controlled trial. SETTING: Community. PARTICIPANTS: Persons (N=39; mean+/-SD age, 74+/-6y; 26 women) with mild to moderate OA and at risk for falling met study criteria, were measured at baseline, and were randomly assigned to the intervention (n=23) and control groups (n=16). INTERVENTIONS: Water-based program (12wk, twice weekly; intervention group) or a time-matched computer training program (control group). MAIN OUTCOME MEASURE: The primary outcome was the short-form Physiological Profile Assessment (PPA). Secondary outcomes included the Step Test, Timed Up and Go Test, Western Ontario and McMaster Universities OA Index (Likert 3.0 version), Arthritis Impact Measurement Scales 2, and Activity-specific Balance Confidence Scale. RESULTS: No statistically significant between-group differences were found for any outcome measured (n=35; 4 lost to follow-up). Within-group analysis indicated that Step Test results improved significantly in both groups (mean change: control group, left leg, 2.07; 95% confidence interval, 3.19-.95; P=.002; intervention group, 2.14; 95% confidence interval, 3.20-1.08; P=.000). Two PPA item scores (reaction time, contrast sensitivity) improved significantly (86.83; 95% confidence interval, 9.86-163.79; P=.03; 1.43; 95% confidence interval, 2.35-.50; P=.005, respectively) in the control group, resulting in a lower falls risk score. CONCLUSIONS: Water-based exercise did not reduce falls risk in our sample compared with attending a computer skills training class. Our study is, to our knowledge, the first to compare water-based exercise in this population with a control group that attended a time-dose-equivalent seated community-based activity. Whether gaining computer skills and going out into the community twice weekly is adequate stimulus to reduce falls risk in people with OA requires further investigation. PMID- 21982327 TI - Advances in anticoagulation: focus on dabigatran, an oral direct thrombin inhibitor. AB - Dabigatran is an oral direct thrombin inhibitor with a rapid onset. Patients on dabigatran do not require coagulation monitoring. Recent prospective randomized trials have shown the efficacy of dabigatran for the prevention of venous thromboembolism after knee or hip arthroplasty and for the prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. Because dabigatran is cleared principally by the kidneys, dosage adjustments are required in the setting of renal dysfunction. There currently is no reversal agent for dabigatran although hemodialysis can facilitate its rapid removal in life-threatening circumstances. The management of severe bleeding associated with dabigatran also may include the administration of a procoagulant, such as recombinant activated factor VII. Based on recent guidelines, regional anesthesia should be used cautiously in patients taking this novel oral thrombin inhibitor. PMID- 21982328 TI - Sudden intraoperative hypertension during endovascular abdominal aortic repair as a first sign of massive fatal atheroembolism. PMID- 21982329 TI - Morphine reduces the threshold of remote ischemic preconditioning against myocardial ischemia and reperfusion injury in rats: the role of opioid receptors. AB - OBJECTIVES: Opioid receptors mediate the cardioprotection of remote ischemic preconditioning (RIPC). The authors tested the hypothesis that morphine reduces the threshold of cardioprotection produced by RIPC. METHODS: A randomized, prospective study. SETTING: A university research laboratory. PARTICIPANTS: Forty five male Sprague-Dawley rats. INTERVENTIONS: Anesthetized, open-chest, male Sprague-Dawley rats were assigned randomly to 1 of 7 treatment groups. RIPC1 and RIPC3 were, respectively, induced by 1 or 3 cycles of 5 minutes of femoral artery ischemia interspersed with 5 minutes of reperfusion. Morphine (MOR, 0.1 mg/kg) and the opioid receptor antagonist naloxone (NAL, 6 mg/kg) were administered 30 minutes before sustaining ischemia. MOR + RIPC1 and NAL + MOR + RIPC1 groups received the combination of MOR and RIPC1 in the absence or presence of NAL before coronary artery occlusion. Ischemia and reperfusion injury then were induced by 30 minutes of left coronary artery occlusion followed by 120 minutes of reperfusion. MEASUREMENTS AND MAIN RESULTS: Infarct size, as a percentage of the area at risk, was determined by 2,3,5-triphenyltetrazolium staining. RIPC3 and the combination of MOR and RIPC1 groups significantly reduced the infarct size compared with the control group. RIPC1, MOR, and NAL did not affect infarct size. NAL pretreatment reversed cardioprotection of the combination of MOR and RIPC1 treatments. CONCLUSIONS: MOR reduces the threshold of RIPC, and opioid receptors mediate this augmentative effect. PMID- 21982330 TI - Paying health workers for performance in Battagram district, Pakistan. AB - BACKGROUND: There is a growing interest in using pay-for-performance mechanisms in low and middle-income countries in order to improve the performance of health care providers. However, at present there is a dearth of independent evaluations of such approaches which can guide understanding of their potential and risks in differing contexts. This article presents the results of an evaluation of a project managed by an international non-governmental organisation in one district of Pakistan. It aims to contribute to learning about the design and implementation of pay-for-performance systems and their impact on health worker motivation. METHODS: Quantitative analysis was conducted of health management information system (HMIS) data, financial records, and project documents covering the period 2007-2010. Key informant interviews were carried out with stakeholders at all levels. At facility level, in-depth interviews were held, as were focus group discussions with staff and community members. RESULTS: The wider project in Battagram had contributed to rebuilding district health services at a cost of less than US$4.5 per capita and achieved growth in outputs. Staff, managers and clients were appreciative of the gains in availability and quality of services. However, the role that the performance-based incentive (PBI) component played was less clear--PBI formed a relatively small component of pay, and did not increase in line with outputs. There was little evidence from interviews and data that the conditional element of the PBIs influenced behaviour. They were appreciated as a top-up to pay, but remained low in relative terms, and only slightly and indirectly related to individual performance. Moreover, they were implemented independently of the wider health system and presented a clear challenge for longer term integration and sustainability. CONCLUSIONS: Challenges for performance-based pay approaches include the balance of rewarding individual versus team efforts; reflecting process and outcome indicators; judging the right level of incentives; allowing for very different starting points and situations; designing a system which is simple enough for participants to comprehend; and the tension between independent monitoring and integration in a national system. Further documentation of process and cost-effectiveness, and careful examination of the wider impacts of paying for performance, are still needed. PMID- 21982331 TI - Microarray-based cancer prediction using single genes. AB - BACKGROUND: Although numerous methods of using microarray data analysis for cancer classification have been proposed, most utilize many genes to achieve accurate classification. This can hamper interpretability of the models and ease of translation to other assay platforms. We explored the use of single genes to construct classification models. We first identified the genes with the most powerful univariate class discrimination ability and then constructed simple classification rules for class prediction using the single genes. RESULTS: We applied our model development algorithm to eleven cancer gene expression datasets and compared classification accuracy to that for standard methods including Diagonal Linear Discriminant Analysis, k-Nearest Neighbor, Support Vector Machine and Random Forest. The single gene classifiers provided classification accuracy comparable to or better than those obtained by existing methods in most cases. We analyzed the factors that determined when simple single gene classification is effective and when more complex modeling is warranted. CONCLUSIONS: For most of the datasets examined, the single-gene classification methods appear to work as well as more standard methods, suggesting that simple models could perform well in microarray-based cancer prediction. PMID- 21982332 TI - Early follow-up and treatment recommendations for isolated calf deep venous thrombosis. AB - BACKGROUND: The clinical significance of isolated calf vein thrombosis (ICVT) remains controversial. Several studies have shown that the majority of ICVT do not propagate above the knee while other studies have suggested ICVT propagation and recommend full anticoagulation. The purpose of this study was to determine the progression of ICVT, identify risk factors for clot propagation, and to evaluate further thrombotic events associated with it. METHODS: This study consisted of 156 patients and a total of 180 limbs. All patients included had ICVT involving either the tibial, peroneal, gastrocnemius, or the soleal vein. After initial diagnosis, all patients were started on prophylactic dose of low molecular weight heparin (LMWH) or unfractionated heparin, unless already anticoagulated. All limbs were monitored using duplex ultrasonography scans at intervals of 2 to 3 days, 1 to 3 months, and 6 to 8 months from the initial time of diagnosis. Outcomes examined included lysis of clot, propagation to a proximal vein, and pulmonary emboli. RESULTS: ICVT was detected in 180 limbs of 156 patients. No significant difference was noted in the gender of the patients or limb preference. Twenty-four patents had both limbs involved. The mean age was 77 years old and the mean follow-up was 5.1 months. The soleal vein was most commonly involved. The second most common vein involved was peroneal, followed by posterior tibial and then gastrocnemius. The least commonly involved vein was the anterior tibial with only one positive result on each side. Fifteen of 180 limbs (9%) had complete resolution of the thrombus within 72 hours. Of these, six were anticoagulated to a therapeutic level. All patients had a follow-up duplex scan within 1 to 3 months' time, and none had recurrence. At the 1 to 3-month follow up, 11 of 180 patients (7%) had propagation to a proximal vein; all of whom were in a high-risk group to develop a deep vein thrombosis (DVT), either after an orthopedic procedure, stroke, or malignancy. Nine of 156 patients developed a pulmonary emboli also diagnosed within the 1 to 3-months' time period. At the 6 to 8-month follow-up, there was no further propagation of any additional limbs and no further incidences of pulmonary emboli. CONCLUSION: ICVT can be safely observed in asymptomatic patients without therapeutic anticoagulation. In our study, patients who have had orthopedic procedures, those with malignancy, and those that were immobile seemed to have a higher incidence of clot propagation. In this group, we recommend full anticoagulation until the patient is ambulatory or the follow-up duplex scan is negative. Our data also suggest that a follow-up duplex scan is not beneficial when performed within 72 hours or after 3 months. PMID- 21982334 TI - Purification, biochemical properties and antithrombotic effect of a novel Streptomyces enzyme on carrageenan-induced mice tail thrombosis model. AB - INTRODUCTION: The prevalence of cardiovascular diseases, one of the major causes of worldwide mortality, is being increasingly reported. Safer, more effective, and less expensive thrombolytic drugs can possibly overcome the underlying problems associate with current thrombolytic drugs. METHODS: A thrombolytic enzyme was purified and characterized from a Streptomyces strain. Carrageenan induced tail-thrombosis mice model was used to evaluate in vivo antithrombotic effect of the enzyme. RESULTS: First 15N-terminal amino acids of the purified enzyme were IAGGQAIYAGGGRRS, which are significantly different from the reported fibrinolytic enzymes. The enzyme exhibited 14.3+/-2.3-fold stronger thrombolytic activity than that of plasmin. In carrageenan induced tail-thrombosis model, the enzyme caused reduction in frequency of thrombus. Tail-thrombus of the enzyme treated group was significantly shorter than the physiological saline treated group and the thrombus decrement was correlated with the enzyme dose. CONCLUSIONS: The enzyme purified from the Streptomyces strain can be a potential candidate for the treatment of thrombosis. PMID- 21982335 TI - Chorioallantoic and yolk sac placentation in the plains viscacha (Lagostomus maximus) - a caviomorph rodent with natural polyovulation. AB - OBJECTIVES: Reproduction in the plains viscacha is characterized by the polyovulation of hundreds of oocytes, the loss of implantation and the development of 1-3 offspring. Our goal was to determine whether placental development was affected by these specializations. STUDY DESIGN: Thirteen placentas from early pregnancy to near-term pregnancy were analyzed using histological, immunohistochemical and transmission electron microscopy. RESULTS: An inverted, villous yolk sac was present. Placentas were formed by the trophospongium, labyrinth and subplacenta. A lobulated structure with a hemomonochorial barrier was established early in pregnancy. Proliferating trophoblast that was clustered at the outer border and inside the labyrinth was responsible for placental growth. Trophoblast invasion resulted from the cellular trophoblast and syncytial streamers derived from the subplacenta. Different from other caviomorphs, numerous giant cells were observed. CONCLUSIONS: The principle processes of placentation in caviomorphs follow an extraordinarily stable pattern that is independent of specializations, such as polyovulation. PMID- 21982336 TI - Multiarmed star-like platinum nanowires with multienzyme assembly for direct electronic determination of carcinoembryoninc antigen in serum. AB - A new electrochemical immunoassay strategy for direct detection of carcinoembryoninc antigen (CEA) in serum was developed by using multiarmed star like platinum nanowires (PtNWs) with biomolecular assembly as signal tags on an anti-CEA-functionalized graphene sensing platform. Initially, the PtNWs were synthesized via a wet chemical method, and then the synthesized PtNWs were used for the co-immobilization of CEA and horseradish peroxidase (HRP). Compared with platinum nanoparticles, the prepared PtNWs could provide a large room for the conjugation of HRP and CEA. With a competitive-type immunoassay format, the assay was performed in two types of supporting electrolytes including new born cattle serum (NBCS) and acetate buffer solution (ABS, pH 5.5), respectively. Similar detection limit (LOD) of 5.0 pg mL(-1) vs. 1.0 pg mL(-1) but narrower dynamic working linear range of 0.01-60 ng mL(-1) vs. 0.002-80 ng mL(-1) was obtained toward CEA standards in the NBCS compared to the ABS. The intra-assay coefficients of variation (CVs) were 4.3%, 8.6%, and 6.2% at 0.05, 10, and 40 ng mL(-1) CEA, respectively, while the inter-assay CVs were 7.6%, 10.5%, and 8.9% at the above-mentioned levels, respectively. In addition, the selectivity and stability of the electrochemical immunosensor were acceptable. Importantly, the developed method was used to assay clinical serum specimens, receiving a good relation with those obtained from the referenced method. PMID- 21982337 TI - Design, synthesis and antibacterial activity of fluoroquinolones containing bulky arenesulfonyl fragment: 2D-QSAR and docking study. AB - Here in, we report the design, synthesis, and antibacterial activity of series of bulky arenesulfonamido derivatives using ciprofloxacin and norfloxacin as scaffolds. All the synthesized compounds were investigated in vitro for their antibacterial activities against two Gram-positive and two Gram-negative organisms using dilution broth method. Among the tested compounds examined, compounds 3-7 showed significance difference from the standard drug ciprofloxacin. 2D-QSAR study provides details on the fine relationship linking structure and activity and offers clues for structural modifications that can improve the activity. Docking study of the compound 3b into the active site of the topoisomerase II DNA-gyrase enzymes revealed a similar binding mode to ciprofloxacin with additional classical and nonclassical hydrogen bonds. PMID- 21982338 TI - Synthesis and antimalarial activity of thioetherhydroxyethylsulfonamides, potential aspartyl protease inhibitors, Part 3. AB - A series of novel thioetherhydroxyethylsulfonamide derivatives has been synthesized from the coupling of intermediates 3-amino-4-phenyl-1-thioetherazine butan-2-oles 6,7 with arenesulfonyl chlorides in good yields. Characterizations of products were achieved by NMR techniques and specifically for compound 8e by X ray crystallography. Preliminary results of antimalarial activity in vitro against the Plasmodium falciparum W2 clone (chloroquine resistant and mefloquine sensitive) showed moderate activity for hydroxyethylsulfonamide 8f. In addition, none of the compounds tested showed cytotoxicity at high concentration tested against HepG2 and BGM cell lines. PMID- 21982339 TI - Syndrome Z: a comparison of prevalence between females and males. PMID- 21982340 TI - Identification of key performance indicators for on-farm animal welfare incidents: possible tools for early warning and prevention. AB - BACKGROUND: The objective of this study was to describe aspects of case study herds investigated by the Department of Agriculture, Fisheries and Food (DAFF) in which animal welfare incidents occurred and to identify key performance indicators (KPIs) that can be monitored to enhance the Early Warning System (EWS). Despite an EWS being in place for a number of years, animal welfare incidents continue to occur. Questionnaires regarding welfare incidents were sent to Superintending Veterinary Inspectors (SVIs), resulting in 18 herds being chosen as case study herds, 12 of which had a clearly defined welfare incident date. For each study herd, data on six potential KPIs were extracted from DAFF databases. The KPIs for those herds with a clearly defined welfare incident date were studied for a consecutive four year window, with the fourth year being the 'incident year', when the welfare incident was disclosed. For study herds without a clearly defined welfare incident date, the KPIs were determined on a yearly basis between 2001 and 2009. RESULTS: We found that the late registration of calves, the use of on-farm burial as a method of carcase disposal, an increasing number of moves to knackeries over time and records of animals moved to 'herd unknown' were notable on the case farms. CONCLUSION: Four KPIs were prominent on the case study farms and warrant further investigation in control herds to determine their potential to provide a framework for refining current systems of early warning and prevention. PMID- 21982341 TI - Spectrophotometric determination of tizanidine and orphenadrine via ion pair complex formation using eosin Y. AB - A simple, sensitive and rapid spectrophotometric method was developed and validated for the determination of two skeletal muscle relaxants namely, tizanidine hydrochloride (I) and orphenadrine citrate (II) in pharmaceutical formulations. The proposed method is based on the formation of a binary complex between the studied drugs and eosin Y in aqueous buffered medium (pH 3.5). Under the optimum conditions, the binary complex showed absorption maxima at 545 nm for tizanidine and 542 nm for orphenadrine. The calibration plots were rectilinear over concentration range of 0.5-8 MUg/mL and 1-12 MUg/mL with limits of detection of 0.1 MUg/mL and 0.3 MUg/mL for tizanidine and orphenadrine respectively. The different experimental parameters affecting the development and stability of the complex were studied and optimized. The method was successfully applied for determination of the studied drugs in their dosage forms; and to the content uniformity test of tizanidine in tablets. PMID- 21982342 TI - INSPIRE: A phase III study of the BLP25 liposome vaccine (L-BLP25) in Asian patients with unresectable stage III non-small cell lung cancer. AB - BACKGROUND: Previous research suggests the therapeutic cancer vaccine L-BLP25 potentially provides a survival benefit in patients with locally advanced unresectable stage III non-small cell lung carcinoma (NSCLC). These promising findings prompted the phase III study, INSPIRE, in patients of East-Asian ethnicity. East-Asian ethnicity is an independent favourable prognostic factor for survival in NSCLC. The favourable prognosis is most likely due to a higher incidence of EGFR mutations among this patient population. METHODS/DESIGN: The primary objective of the INSPIRE study is to assess the treatment effect of L BLP25 plus best supportive care (BSC), as compared to placebo plus BSC, on overall survival time in East-Asian patients with unresectable stage III NSCLC and either documented stable disease or an objective response according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria following primary chemoradiotherapy. Those in the L-BLP25 arm will receive a single intravenous infusion of cyclophosphamide (300 mg/m2) 3 days before the first L-BLP25 vaccination, with a corresponding intravenous infusion of saline to be given in the control arm. A primary treatment phase of 8 subcutaneous vaccinations of L BLP25 930 MUg or placebo at weekly intervals will be followed by a maintenance treatment phase of 6-weekly vaccinations continued until disease progression or discontinuation from the study. DISCUSSION: The ongoing INSPIRE study is the first large study of a therapeutic cancer vaccine specifically in an East-Asian population. It evaluates the potential of maintenance therapy with L-BLP25 to prolong survival in East-Asian patients with stage III NSCLC where there are limited treatment options currently available. STUDY NUMBER: EMR 63325-012 TRIAL REGISTRATION: Clinicaltrials.gov reference: NCT01015443. PMID- 21982343 TI - Developing vaccine policy: attributes of "just policy" and a proposed template to guide decision and policy making. PMID- 21982344 TI - In-hospital informal caregivers' needs as perceived by themselves and by the nursing staff in Northern Greece: A descriptive study. AB - BACKGROUND: Informal care is common in many countries, especially in Greece, where families provide care in hospitals. Health education and informational needs are important factors for family members which are often underestimated by nursing staff. The aim of this study was to compare the perceptions of the nurses and the in-hospital informal caregivers about the in-hospital informal caregivers' knowledge and informational needs, as well as the factors that influence these perceptions. METHODS: This was a non-experimental descriptive study conducted in three general hospitals in Greece. The sample consisted of 320 nurses and 370 in-hospital informal caregivers who completed questionnaires. Descriptive statistics were analyzed using t-tests; group comparisons were conducted using ANOVA. RESULTS: The score of the questionnaire for health education and informational needs was significantly greater for informal caregivers (57.1 +/- 6.9 and 26.6 +/- 2.8) than for nurses (53.4 +/- 5.7 and 22.4 +/- 3.1) (p < 0.001). For the nursing staff, the factors that influence the informational needs of patients' caregivers were level of education and working experience, while for the caregivers the level of education was independently associated with the score for the health education needs. Finally, age, marital status, and level of education of informal caregivers' were independently associated with informational needs. CONCLUSIONS: The in-hospital informal caregivers perceived that they have more educational and informational needs than the nurses did. The findings of this study also show that the nursing staff has to identify the needs of in-hospital informal caregivers in order to be able to meet these needs. PMID- 21982345 TI - Cognitive behavioural treatment for chronic fatigue syndrome in a rehabilitation setting: effectiveness and predictors of outcome. AB - Cognitive behavioural therapy (CBT) was combined with graded exercise therapy (GET) for patients with chronic fatigue syndrome (CFS) in an uncontrolled implementation study of an inpatient multidisciplinary group therapy. During the intake procedure, 160 CFS patients completed a questionnaire on fatigue related measurements, physical impairment, depression, somatic and psychological attributions, somatic focus, and sense of control over symptoms. Pre-treatment physical activity level was measured with an actometer. At baseline, post treatment and 6-month follow-up individual strength, subjective fatigue and physical impairment, were reassessed. Large effect sizes were found on subjective fatigue (1.2 post-treatment; 1.2 follow-up) and physical impairment (-.9 post treatment; -.9 follow-up), Clinically significant improvement was found in 33.8% of the participants at post-treatment and 30.6% at follow-up. Individual strength at post-treatment was predicted by level of physical activity before treatment, and by sense of control over symptoms and physical activity at follow-up. Clinically significant improvement in subjective fatigue was predicted by not receiving a disablement insurance benefit, shorter duration of fatigue, higher sense of control over symptoms and, at follow-up by more pre-treatment physical activity. In conclusion, the intervention was effective for CFS patients. Cognitive behavioural factors that perpetuate fatigue symptoms are also predictors of treatment outcome. PMID- 21982346 TI - Why does the north-south gradient of incidence of multiple sclerosis seem to have disappeared on the northern hemisphere? AB - The traditional view, based on numerous early studies and reviews, is that MS is particularly prevalent in temperate zones both on the northern and southern hemisphere. This uneven distribution of MS can be attributed to differences in genes and environment and their interaction. Diagnostic accuracy and case ascertainment are sources of error and have their shares in the geographical and temporal variations, and improvements in diagnostic accuracy and case ascertainment influence incidence- and prevalence rates. In addition the prevalence also depends on survival. With this meta-analysis we have focused on the trend in the incidence and sex ratio of MS through the last five decades, and we have analyzed the latitudinal distribution of MS incidence, based on a recent literature search. Our findings indicated that the prevalence and incidence rates had increased in almost all areas, but the previously reported latitudinal gradient of incidence of MS in Europe and North America could not be confirmed even when restricting the search to surveys published before 1980 or 1970. Conversely, the latitudinal gradient of prevalence rates seemed to be preserved. This apparent discrepancy can be explained by the circumstance that incidence estimates only depend on complete ascertainment for a relative short recent period of time, whereas reliable prevalence rates presuppose complete ascertainment decades back in time. A contributory explanation for the missing latitudinal gradient for incidence may be changes in environmental factors, levelling out differences in habits of life across Europe and North America, and, not least, that the interpretation of a latitudinal gradient in Europe was based primarily on prevalence studies and reviews. In addition, we observed in most regions a profound increase in female incidence of MS. The last observation should prompt epidemiological studies focusing on change in female life style. PMID- 21982347 TI - Risk factors for revision surgery after humeral head replacement: 1,431 shoulders over 3 decades. AB - HYPOTHESIS: To assess the long-term risk of revision surgery and its predictors after humeral head replacement (HHR). METHODS: We used prospectively collected data from the Mayo Clinic Total Joint Registry and other institutional electronic databases. Revision-free survival for HHR at 5, 10, and 20 years was calculated by use of Kaplan-Meier survival analysis. We used univariate and multivariate adjusted Cox regression analyses to examine the association of age, gender, body mass index (BMI), comorbidity assessed by Deyo-Charlson index, American Society of Anesthesiologists class, implant fixation (cemented vs uncemented), and underlying diagnosis with the risk of revision surgery. Hazard ratios with 95% confidence intervals (CIs) and P values are presented. RESULTS: During the study period (1976-2008), 1,359 patients underwent 1,431 shoulder HHRs. The mean age was 63 years, 63% of patients were female, the mean BMI was 28 kg/m(2), and 60% of implants were cemented. During the follow-up, 114 HHRs were revised. At 5, 10, and 20 years, the shoulder implant survival rate was 93.6% (95% CI, 92.1%-95%), 90% (95% CI, 88%-92%), and 85% (95% CI, 81.8%-88.4%), respectively. In multivariate-adjusted analyses, older age was associated with a lower hazard of revision, with a hazard ratio of 0.97 (95% CI, 0.96-0.99; P < .001), and higher BMI was associated with a higher hazard ratio of 1.04 (95% CI, 1.01-1.08; P = .02). CONCLUSIONS: Long-term survival of HHR at 20 years was excellent. Obesity and younger age are risk factors for a higher revision rate after HHR. Further studies should investigate the biologic rationale for these important associations. Surgeons can discuss these differences in revision risk with patients, especially young obese patients. PMID- 21982348 TI - Treatment of persistent instability after posterior fracture-dislocation of the elbow: restoring stability and mobility by internal fixation and hinged external fixation. AB - BACKGROUND: Long-term results after the treatment of fracture-dislocations of the elbow have often been disappointing, because of post-traumatic instability, stiffness, and early arthritis. We present the results after surgical restoration of stability in complex fracture-dislocations of the elbow using early postoperative mobilization with a hinged external fixator after internal reconstruction of the static stabilizers. METHODS: Twenty patients with persistent instability after fracture-dislocation of the elbow were treated at a mean of 11 weeks after injury. We evaluated 17 elbows in 16 patients (mean age, 44 years) at a mean of 44 months after the definitive surgical procedure. RESULTS: Overall, 10 of 17 elbows had a good or excellent result. The mean range of motion was 96 degrees (SD, 23 degrees ). The mean Mayo Elbow Performance Score (MEPS) was 74 (SD, 18), and the mean Functional Elbow Score was 68 (SD, 21). Patients treated within 6 weeks after the trauma had significantly better scores, with a mean MEPS of 81 (SD, 18), than patients treated after a delay, with a mean MEPS of 62 (SD, 13). No patients had recurrent dislocation. Secondary arthritis was mainly found in the delayed-treatment group. Of 17 elbows, 7 (41%) had complications. CONCLUSION: Surgical restoration of the static stabilizers in combination with hinged external fixation leads to satisfactory results when performed within the first 6 weeks after injury. When definite surgical stabilization is delayed more than 6 weeks, the procedure can still restore stability but the functional results are often disappointing. PMID- 21982349 TI - Treatment of bone nonunion and bone defects associated with unsuccessful humeral condylar fracture repair with autogenous iliac bone reconstruction. AB - BACKGROUND: Our preliminary study retrospectively assessed outcomes after the use of autogenous iliac bone grafts combined with internal fixation to repair refractory bone nonunions and bone defects associated with supracondylar or intracondylar humeral fractures, or both. MATERIALS AND METHODS: We identified 22 patients (14 men and 8 women) with a mean age of 33.8 years (range, 17-60 years) with bone nonunion and severe bone defects associated with supracondylar or intercondylar humerus fractures, or both. The humeral condyle in each patient was anatomically reconstructed using autologous iliac bone grafts and internal fixation. Active functional exercise was initiated 3 to 4 weeks after surgery. The following variables were assessed: preoperative and postoperative elbow range of motion, Mayo Elbow Performance Score (MEPS), and postoperative complications. RESULTS: Mean follow-up was 38.6 months. Mean duration until bone union was 5.6 months. Preoperatively, 16 patients had a fair or poor MEPS (<75). At final follow-up MEPS was excellent (>90) in 8, good (75-90) in 9, fair (60-74) in 4, and poor (<60) in 1 patient. Postoperative heterotopic ossification anterior to the elbow joint occurred in 2 patients. CONCLUSIONS: Our preliminary results suggest that anatomic reconstruction of the humeral condyle using autogenous iliac bone grafting with internal fixation can improve elbow joint function in patients with bone nonunion and bone defects associated with supracondylar or intracondylar humeral fractures, or both. Larger scale studies are warranted to confirm our findings and compare the efficacy of this vs other surgical approaches. PMID- 21982350 TI - Biomechanical comparison of lesser tuberosity osteotomy versus subscapularis tenotomy in total shoulder arthroplasty. AB - BACKGROUND: Total shoulder arthroplasty is traditionally performed through an anterior deltopectoral exposure with subscapularis tenotomy. Postoperative subscapularis dysfunction is common and adversely affects clinical outcomes. Consequently, surgeon interest in lesser tuberosity osteotomy has grown in an effort to improve subscapularis repair strength. This study investigated the biomechanical strength of subscapularis tenotomy vs lesser tuberosity osteotomy in the setting of total shoulder arthroplasty. MATERIALS AND METHODS: Uncemented humeral prostheses were placed in 20 paired upper extremities from 10 cadavers. For each respective cadaver, 1 limb underwent lesser tuberosity osteotomy and the contralateral limb underwent subscapularis tenotomy. The cadaveric specimens then underwent cyclic displacement and maximum load to failure testing. RESULTS: The subscapularis tenotomy specimens exhibited significantly less cyclic displacement (0.8 mm) than the osteotomy group (1.8 mm), with a 95% confidence interval (CI) for the difference of 0.5 to 1.5 mm (P = 0.002). The maximum load to failure was 439 +/- 96 N for tenotomy and 447 +/- 89 N for osteotomy (95% CI for the difference of -58 to 75), which was not significant (P = .78). CONCLUSION: Lesser tuberosity osteotomy was not significantly stronger than subscapularis tenotomy in maximum load to failure testing, with minimal clinical significance set at 100 N. Subscapularis tenotomy repair showed statistically significant less cyclic displacement than lesser tuberosity osteotomy. Further research is needed to clarify how the biomechanical results immediately after subscapularis tenotomy and lesser tuberosity osteotomy correlate with clinical outcomes. PMID- 21982351 TI - Skin moisturizing effects of panthenol-based formulations. AB - This study aims to evaluate the skin moisturizing efficacy of formulations containing different concentrations of panthenol. Formulations supplemented with or without 0.5%, 1.0%, or 5.0% panthenol were applied daily to the forearms of healthy subjects. Skin conditions in terms of moisture and transepidermal water loss (TEWL) were analyzed before and after 15- and 30-day periods of application. The formulations were also applied after skin washing with sodium laureth sulphate (SLES) to evaluate the immediate effects on TEWL and skin moisture. Panthenol-containing formulations (1.0% and 5.0%) produced significant decreases in TEWL after 30-day applications. In skin washed with SLES, significant reduction of TEWL was evident two hours after application of formulations loaded with panthenol when compared with control and vehicle. It is concluded that skin integrity is maintained by the improved protective effect of 1.0% panthenol added to the formulation. PMID- 21982352 TI - Elaboration, characterization, and stability study of a sunscreen emulsion for use as a towelette application in pediatric photoprotection. AB - The World Health Organization (WHO) estimates that as much as 80% of the solar radiation that an adult receives throughout his/her life is received during the first 18 years (1). Skin protection against harmful solar radiation during this early stage of life is therefore a highly important factor in the prevention of future skin-related diseases. In this respect, recent developments in pediatric dermatology and cosmetic technology have led to remarkable improvements in child skin protection products. However, in spite of these scientific breakthroughs, many currently available commercial sunscreen formulations have not been well received by the general public, due to inadequate sensory properties, chemical instability, undesirable side effects, and low effectiveness. These disadvantages are not only attributable to the formulations themselves, active principle, and excipients, but also, to a large extent, galenic aspects. The objective of this work was to develop and characterize a sunscreen emulsion for pediatric use, using a towelette as vehicle, to overcome problems of ineffectiveness and formulation instability, and to improve skin-sensory properties. The composition of the towelette, the emulsion, and the presentation format were selected on the basis of the differences between children's and adult skin. In order to evaluate the chemical stability of the formulation, a study of the organoleptic, physicochemical, microbiological, and rheological characteristics was carried out at 4 degrees , 25 degrees , and 40 degrees C over a period of 30 days. Tests were performed on both the sunscreen emulsion only and the same formulation impregnated within a towel, to test the influence the towel may have on the stability of the emulsion. PMID- 21982353 TI - The uptake of water hardness metals by human hair. AB - The objective of this work was to examine the variables that influence the interaction between water hardness metals and human hair. Hair extracts various constituents from the tap water used during daily hygiene practices and chemical treatments. Calcium and magnesium metal ions are the most prevalent and give water "hardness." Inductively coupled plasma atomic emission spectroscopy (ICP AES) was employed to quantify the metal content of hair, which was studied as a function of the following variables: hair condition (oxidative damage), level of water hardness, and water pH. We have demonstrated that these variables impact water hardness metal uptake to varying extents, and the effects are driven primarily by the binding capacity (available anionic sites) of the hair. The condition of the hair, a key representation of the binding capacity, was most influential. Interestingly, water hardness levels had only a small effect on uptake; hair became saturated with notable amounts of water hardness metals even after repeated exposure to soft water. Water pH influenced metal uptake since side chains of hair proteins deprotonate with increasing alkalinity. These insights highlight the importance to the hair care industry of understanding the interaction between water hardness metals and hair. PMID- 21982354 TI - A study of four antioxidant activities and major chemical component analyses of twenty-five commonly used essential oils. AB - Twenty-five essential oils and their major chemical components were screened for their possible antioxidant activities by assaying their DPPH free-radical scavenging activity (DFRS), total phenolic contents (TPC), trolox equivalent antioxidant capacity (TEAC), and ferric thiocyanate (FTC). Based on the TPC and TEAC assays, the essential oil ajowan is among the best essential oils studied. Furthermore, the DFRS and FTC assays reveal that the essential oils cinnamon bark extra and oregano are also among the best oils studied. More specifically, at a concentration of 1 mg ml(-1), the essential oils cinnamon bark extra and benzoin showed 93.75 +/- 0.01% and 90.64 +/- 0.01% DFRS, while the essential oils ajowan and oregano showed TEAC values of 4374.72 +/- 0.01 and 4023.49 +/- 0.01 MUM of trolox per mg, respectively. In addition, the essential oils oregano and ajowan showed 29.17 +/- 0.02% and 25.26 +/- 0.03% FTC based on the assay results. At a concentration of 10 mg ml(-1), the essential oils ajowan and oregano showed 1845.20 +/- 0.04 and 1665.36 +/- 0.04 MUg of TPC relative to GAE, respectively. Two major chemical components of the essential oils cinnamon bark extra, ajowan, and oregano were trans-cinnamaldehyde (90.61%), eugenol (2.58%), carvacrol (61.20%), p-cymene (37.44%), thymol (77.09%), and p-cymene (10.01%). It is clear that phenolic compounds in the aforementioned essential oils yield a positive correlation with the DFRS, TPC, TEAC, and FTC assays. PMID- 21982355 TI - Vitamin A palmitate and alpha-lipoic acid stability in o/w emulsions for cosmetic application. AB - Skin becomes thin, dry, pale, and finely wrinkled with age. Retinoids are a large class of compounds that are important in modern therapy for dermatological treatment of wrinkled skin. Of the retinoids, retinol and vitamin A palmitate are thought to induce thickening of the epidermis and to be effective for treatment of skin diseases. Accordingly, alpha-lipoic acid or the reduced form, dihydrolipoate, are potent scavengers of hydroxyl radicals, superoxide radicals, peroxyl radicals, singlet oxygen, and nitric oxide with anti-inflammatory properties (1). Cosmetic ingredient stability prediction relies on kinetic quantitative chemical analysis of active components at different temperatures. Vitamin A palmitate and alpha-lipoic acid, are known to be unstable to light or heat (2). The aims of this study were to evaluate the stability of alpha-lipoic acid and vitamin A palmitate in the presence of vitamin E (acetate) and other antioxidants in lipophilic/hydrophilic medium (O/W emulsions) at pH 3.0, 5.0, and 7.0. The formulations that were investigated contained 0.12% (w/w) vitamin A palmitate, 0.4% (w/w) vitamin E acetate, and 0.5 % alpha-lipoic acid (formulation A), supplemented with ascorbyl palmitate, magnesium ascorbyl phosphate, and vitamin C (formulation B) or with butylhydroxytoluene (BHT, formulation C) or ascorbyl palmitate (formulation D). The chemical analyses of alpha-lipoic acid and vitamin A palmitate were carried out by HPLC. Formulations C and D at pH 7.0 were selected as the most stable for these components. The purpose of this paper is the selection of the most stable formulations for their application in in vivo studies. PMID- 21982358 TI - PI and fuzzy logic controllers for shunt Active Power Filter--a report. AB - This paper presents a shunt Active Power Filter (APF) for power quality improvements in terms of harmonics and reactive power compensation in the distribution network. The compensation process is based only on source current extraction that reduces the number of sensors as well as its complexity. A Proportional Integral (PI) or Fuzzy Logic Controller (FLC) is used to extract the required reference current from the distorted line-current, and this controls the DC-side capacitor voltage of the inverter. The shunt APF is implemented with PWM current controlled Voltage Source Inverter (VSI) and the switching patterns are generated through a novel Adaptive-Fuzzy Hysteresis Current Controller (A-F-HCC). The proposed adaptive-fuzzy-HCC is compared with fixed-HCC and adaptive-HCC techniques and the superior features of this novel approach are established. The FLC based shunt APF system is validated through extensive simulation for diode rectifier/R-L loads. PMID- 21982359 TI - Successful bridge to transplantation for pediatric lupus cardiomyopathy. PMID- 21982360 TI - Skeletal muscle microcirculatory abnormalities are associated with exercise intolerance, ventilatory inefficiency, and impaired autonomic control in heart failure. AB - BACKGROUND: Several skeletal muscle abnormalities have been identified in patients with chronic heart failure (CHF), including endothelial dysfunction. We hypothesized that skeletal muscle microcirculation, assessed by near-infrared spectroscopy (NIRS), is impaired in CHF patients and is associated with disease severity. METHODS: Eighty-three stable patients with mild-moderate CHF (72 males, mean age 54 +/- 14 years, body mass index 26.7 +/- 3.4 kg/m(2)) and 8 healthy subjects, matched for age, gender and body mass index, underwent NIRS with the vascular occlusion technique and cardiopulmonary exercise testing (CPET) evaluation on the same day. Tissue oxygen saturation (StO(2), %), defined as the percentage of hemoglobin saturation in the microvasculature compartments, was measured in the thenar muscle by NIRS before, during and after 3-minute occlusion of the brachial artery. Measurements included StO(2), oxygen consumption rate (OCR, %/min) and reperfusion rate (RR, %/min). All subjects underwent a symptom limited CPET on a cycle ergometer. Measurements included VO(2) at peak exercise (VO(2)peak, ml/kg/min) and anaerobic threshold (VO(2)AT, ml/kg/min), VE/VCO(2) slope, chronotropic reserve (CR, %) and heart rate recovery (HRR(1), bpm). RESULTS: CHF patients had significantly lower StO(2) (75 +/- 8.2 vs 80.3 +/- 6, p < 0.05), lower OCR (32.3 +/- 10.4 vs 37.7 +/- 5.5, p < 0.05) and lower RR (10 +/- 2.8 vs 15.7 +/- 6.3, p < 0.05) compared with healthy controls. CHF patients with RR >=9.5 had a significantly greater VO(2)peak (p < 0.001), VO(2)AT (p < 0.01), CR (p = 0.01) and HRR(1) (p = 0.01), and lower VE/VCO(2) slope (p = 0.001), compared to those with RR <9.5. In a multivariate analysis, RR was identified as an independent predictor of VO(2)peak, VE/VCO(2) slope and HRR(1). CONCLUSIONS: Peripheral muscle microcirculation, as assessed by NIRS, is significantly impaired in CHF patients and is associated with disease severity. PMID- 21982362 TI - Long-range intracortical excitation shapes olfactory processing. AB - Recurrent intracortical connections are believed to be especially dense in the piriform cortex. Two studies in this issue of Neuron report several interesting features of the long-range intracortical connections and reveal their physiological roles in shaping olfactory processing. PMID- 21982361 TI - Association between modifiable lifestyle factors and residual lifetime risk of diabetes. AB - BACKGROUND AND AIMS: While clinical trials have reported beneficial effects of diet, exercise, and weight loss on incident diabetes in subjects with obesity or impaired glucose tolerance, little is known about the incremental benefit of not smoking and moderate drinking on diabetes risk. We sought to examine the association between modifiable lifestyle factors and residual lifetime risk of diabetes. METHODS AND RESULTS: Prospective cohorts involving 20,915 men (1982 2008) and 36,594 women (1992-2008). Modifiable lifestyle factors and adiposity were ascertained at baseline in each cohort and incident diabetes was ascertained during follow up. The mean age at baseline was 53.5 y in men and 54.6 y in women. During an average follow up of 22.6 y in men and 13.0 y in women, 2096 men and 2390 women developed diabetes. At age 45 y, the residual lifetime risk of diabetes (95% CI) for men with 0, 1, 2, 3, and 4 + healthy lifestyle factors was 30.5 (27.3-33.7); 21.5 (19.9-23.0); 15.1 (13.9-16.3); 10.3 (9.1-11.5); and 7.3 (5.7-8.9) percent; respectively. Corresponding values for women were 31.4 (28.3 34.5); 24.1 (21.8-26.5); 14.2 (12.7-15.7); 11.6 (9.7-13.5); and 6.4 (4.2-8.6) percent, respectively. CONCLUSIONS: These data show an inverse and graded relation between desirable lifestyle factors and residual lifetime risk of diabetes in men and women. Not smoking and moderate drinking may have additional benefits when added to exercise, weight control, and diet. PMID- 21982363 TI - MeCP2: phosphorylated locally, acting globally. AB - In this issue of Neuron, Greenberg and colleagues revise our understanding of how activity-dependent MeCP2 phosphorylation regulates distinct aspects of brain development and circuit function. The study also suggests a prominent role for MeCP2 in the regulation of global chromatin state in vivo. PMID- 21982364 TI - Polyrhythms of the brain. AB - The mechanism by which multiple brain structures interact to support working memory is not yet fully understood. In this issue of Neuron, Fujisawa and Buzsaki report that coordinated oscillatory activities between the hippocampus, prefrontal cortex, and ventral tegmental area (VTA) may be a key neural correlate of working memory. PMID- 21982365 TI - Protease regulation: the Yin and Yang of neural development and disease. AB - The formation, maintenance, and plasticity of neural circuits rely upon a complex interplay between progressive and regressive events. Increasingly, new functions are being identified for axon guidance molecules in the dynamic processes that occur within the embryonic and adult nervous system. The magnitude, duration, and spatial activity of axon guidance molecule signaling are precisely regulated by a variety of molecular mechanisms. Here we focus on recent progress in understanding the role of protease-mediated cleavage of guidance factors required for directional axon growth, with a particular emphasis on the role of metalloprotease and gamma-secretase. Since axon guidance molecules have also been linked to neural degeneration and regeneration in adults, studies of guidance receptor proteolysis are beginning to define new relationships between neurodevelopment and neurodegeneration. These findings raise the possibility that the signaling checkpoints controlled by proteases could be useful targets to enhance regeneration. PMID- 21982367 TI - A major role for intracortical circuits in the strength and tuning of odor-evoked excitation in olfactory cortex. AB - In primary sensory cortices, there are two main sources of excitation: afferent sensory input relayed from the periphery and recurrent intracortical input. Untangling the functional roles of these two excitatory pathways is fundamental for understanding how cortical neurons process sensory stimuli. Odor representations in the primary olfactory (piriform) cortex depend on excitatory sensory afferents from the olfactory bulb. However, piriform cortex pyramidal cells also receive dense intracortical excitatory connections, and the relative contribution of these two pathways to odor responses is unclear. Using a combination of in vivo whole-cell voltage-clamp recording and selective synaptic silencing, we show that the recruitment of intracortical input, rather than olfactory bulb input, largely determines the strength of odor-evoked excitatory synaptic transmission in rat piriform cortical neurons. Furthermore, we find that intracortical synapses dominate odor-evoked excitatory transmission in broadly tuned neurons, whereas bulbar synapses dominate excitatory synaptic responses in more narrowly tuned neurons. PMID- 21982366 TI - Transcriptional regulation of neuronal polarity and morphogenesis in the mammalian brain. AB - The highly specialized morphology of a neuron, typically consisting of a long axon and multiple branching dendrites, lies at the core of the principle of dynamic polarization, whereby information flows from dendrites toward the soma and to the axon. For more than a century, neuroscientists have been fascinated by how shape is important for neuronal function and how neurons acquire their characteristic morphology. During the past decade, substantial progress has been made in our understanding of the molecular underpinnings of neuronal polarity and morphogenesis. In these studies, transcription factors have emerged as key players governing multiple aspects of neuronal morphogenesis from neuronal polarization and migration to axon growth and pathfinding to dendrite growth and branching to synaptogenesis. In this review, we will highlight the role of transcription factors in shaping neuronal morphology with emphasis on recent literature in mammalian systems. PMID- 21982368 TI - Recurrent circuitry dynamically shapes the activation of piriform cortex. AB - In the piriform cortex, individual odorants activate a unique ensemble of neurons that are distributed without discernable spatial order. Piriform neurons receive convergent excitatory inputs from random collections of olfactory bulb glomeruli. Pyramidal cells also make extensive recurrent connections with other excitatory and inhibitory neurons. We introduced channelrhodopsin into the piriform cortex to characterize these intrinsic circuits and to examine their contribution to activity driven by afferent bulbar inputs. We demonstrated that individual pyramidal cells are sparsely interconnected by thousands of excitatory synaptic connections that extend, largely undiminished, across the piriform cortex, forming a large excitatory network that can dominate the bulbar input. Pyramidal cells also activate inhibitory interneurons that mediate strong, local feedback inhibition that scales with excitation. This recurrent network can enhance or suppress bulbar input, depending on whether the input arrives before or after the cortex is activated. This circuitry may shape the ensembles of piriform cells that encode odorant identity. PMID- 21982369 TI - Exogenous alpha-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. AB - Inclusions composed of alpha-synuclein (alpha-syn), i.e., Lewy bodies (LBs) and Lewy neurites (LNs), define synucleinopathies including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Here, we demonstrate that preformed fibrils generated from full-length and truncated recombinant alpha-syn enter primary neurons, probably by adsorptive-mediated endocytosis, and promote recruitment of soluble endogenous alpha-syn into insoluble PD-like LBs and LNs. Remarkably, endogenous alpha-syn was sufficient for formation of these aggregates, and overexpression of wild-type or mutant alpha-syn was not required. LN-like pathology first developed in axons and propagated to form LB-like inclusions in perikarya. Accumulation of pathologic alpha-syn led to selective decreases in synaptic proteins, progressive impairments in neuronal excitability and connectivity, and, eventually, neuron death. Thus, our data contribute important insights into the etiology and pathogenesis of PD-like alpha-syn inclusions and their impact on neuronal functions, and they provide a model for discovering therapeutics targeting pathologic alpha-syn-mediated neurodegeneration. PMID- 21982370 TI - Genome-wide activity-dependent MeCP2 phosphorylation regulates nervous system development and function. AB - Autism spectrum disorders such as Rett syndrome (RTT) have been hypothesized to arise from defects in experience-dependent synapse maturation. RTT is caused by mutations in MECP2, a nuclear protein that becomes phosphorylated at S421 in response to neuronal activation. We show here that disruption of MeCP2 S421 phosphorylation in vivo results in defects in synapse development and behavior, implicating activity-dependent regulation of MeCP2 in brain development and RTT. We investigated the mechanism by which S421 phosphorylation regulates MeCP2 function and show by chromatin immunoprecipitation-sequencing that this modification occurs on MeCP2 bound across the genome. The phosphorylation of MeCP2 S421 appears not to regulate the expression of specific genes; rather, MeCP2 functions as a histone-like factor whose phosphorylation may facilitate a genome-wide response of chromatin to neuronal activity during nervous system development. We propose that RTT results in part from a loss of this experience dependent chromatin remodeling. PMID- 21982371 TI - Intrinsic epigenetic factors cooperate with the steroid hormone ecdysone to govern dendrite pruning in Drosophila. AB - Pruning that selectively removes unnecessary axons/dendrites is crucial for sculpting neural circuits during development. During Drosophila metamorphosis, dendritic arborization sensory neurons, ddaCs, selectively prune their larval dendrites in response to the steroid hormone ecdysone. However, it is unknown whether epigenetic factors are involved in dendrite pruning. Here, we analyzed 81 epigenetic factors, from which a Brahma (Brm)-containing chromatin remodeler and a histone acetyltransferase CREB-binding protein (CBP) were identified for their critical roles in initiating dendrite pruning. Brm and CBP specifically activate a key ecdysone response gene, sox14, but not EcR-B1. Furthermore, the HAT activity of CBP is important for sox14 expression and dendrite pruning. EcR-B1 associates with CBP in the presence of ecdysone, which is facilitated by Brm, resulting in local enrichment of an active chromatin mark H3K27Ac at the sox14 locus. Thus, specific intrinsic epigenetic factors cooperate with steroid hormones to activate selective transcriptional programs, thereby initiating neuronal remodeling. PMID- 21982372 TI - Rod vision is controlled by dopamine-dependent sensitization of rod bipolar cells by GABA. AB - Dark and light adaptation of retinal neurons allow our vision to operate over an enormous light intensity range. Here we report a mechanism that controls the light sensitivity and operational range of rod-driven bipolar cells that mediate dim-light vision. Our data indicate that the light responses of these cells are enhanced by sustained chloride currents via GABA(C) receptor channels. This sensitizing GABAergic input is controlled by dopamine D1 receptors, with horizontal cells serving as a plausible source of GABA release. Our findings expand the role of dopamine in vision from its well-established function of suppressing rod-driven signals in bright light to enhancing the same signals under dim illumination. They further reveal a role for GABA in sensitizing the circuitry for dim-light vision, thereby complementing GABA's traditional role in providing dynamic feedforward and feedback inhibition in the retina. PMID- 21982374 TI - Sparse incomplete representations: a potential role of olfactory granule cells. AB - Mitral/tufted cells of the olfactory bulb receive odorant information from receptor neurons and transmit this information to the cortex. Studies in awake behaving animals have found that sustained responses of mitral cells to odorants are rare, suggesting sparse combinatorial representation of the odorants. Careful alignment of mitral cell firing with the phase of the respiration cycle revealed brief transient activity in the larger population of mitral cells, which respond to odorants during a small fraction of the respiration cycle. Responses of these cells are therefore temporally sparse. Here, we propose a mathematical model for the olfactory bulb network that can reproduce both combinatorially and temporally sparse mitral cell codes. We argue that sparse codes emerge as a result of the balance between mitral cells' excitatory inputs and inhibition provided by the granule cells. Our model suggests functional significance for the dendrodendritic synapses mediating interactions between mitral and granule cells. PMID- 21982373 TI - Long-range neuronal circuits underlying the interaction between sensory and motor cortex. AB - In the rodent vibrissal system, active sensation and sensorimotor integration are mediated in part by connections between barrel cortex and vibrissal motor cortex. Little is known about how these structures interact at the level of neurons. We used Channelrhodopsin-2 (ChR2) expression, combined with anterograde and retrograde labeling, to map connections between barrel cortex and pyramidal neurons in mouse motor cortex. Barrel cortex axons preferentially targeted upper layer (L2/3, L5A) neurons in motor cortex; input to neurons projecting back to barrel cortex was particularly strong. Barrel cortex input to deeper layers (L5B, L6) of motor cortex, including neurons projecting to the brainstem, was weak, despite pronounced geometric overlap of dendrites with axons from barrel cortex. Neurons in different layers received barrel cortex input within stereotyped dendritic domains. The cortico-cortical neurons in superficial layers of motor cortex thus couple motor and sensory signals and might mediate sensorimotor integration and motor learning. PMID- 21982375 TI - Coherent phasic excitation during hippocampal ripples. AB - High-frequency hippocampal network oscillations, or "ripples," are thought to be involved in episodic memory. According to current theories, memory traces are represented by assemblies of principal neurons that are activated during ripple associated network states. Here we performed in vivo and in vitro experiments to investigate the synaptic mechanisms during ripples. We discovered postsynaptic currents that are phase-locked to ripples and coherent among even distant CA1 pyramidal neurons. These fast currents are consistent with excitatory postsynaptic currents (EPSCs) as they are observed at the equilibrium potential of Cl(-), and they display kinetics characteristic of EPSCs. Furthermore, they survived after intracellular blockade of GABAergic transmission and are effective to regulate the timing of action potentials. In addition, our data show a progressive synchronization of phasic excitation and inhibition during the course of ripples. Together, our results demonstrate the presence of phasic excitation during ripples reflecting an exquisite temporal coordination of assemblies of active pyramidal cells. PMID- 21982376 TI - A 4 Hz oscillation adaptively synchronizes prefrontal, VTA, and hippocampal activities. AB - Network oscillations support transient communication across brain structures. We show here, in rats, that task-related neuronal activity in the medial prefrontal cortex (PFC), the hippocampus, and the ventral tegmental area (VTA), regions critical for working memory, is coordinated by a 4 Hz oscillation. A prominent increase of power and coherence of the 4 Hz oscillation in the PFC and the VTA and its phase modulation of gamma power in both structures was present in the working memory part of the task. Subsets of both PFC and hippocampal neurons predicted the turn choices of the rat. The goal-predicting PFC pyramidal neurons were more strongly phase locked to both 4 Hz and hippocampal theta oscillations than nonpredicting cells. The 4 Hz and theta oscillations were phase coupled and jointly modulated both gamma waves and neuronal spikes in the PFC, the VTA, and the hippocampus. Thus, multiplexed timing mechanisms in the PFC-VTA-hippocampus axis may support processing of information, including working memory. PMID- 21982377 TI - Ubiquity and specificity of reinforcement signals throughout the human brain. AB - Reinforcements and punishments facilitate adaptive behavior in diverse domains ranging from perception to social interactions. A conventional approach to understanding the corresponding neural substrates focuses on the basal ganglia and its dopaminergic projections. Here, we show that reinforcement and punishment signals are surprisingly ubiquitous in the gray matter of nearly every subdivision of the human brain. Humans played either matching-pennies or rock paper-scissors games against computerized opponents while being scanned using fMRI. Multivoxel pattern analysis was used to decode previous choices and their outcomes, and to predict upcoming choices. Whereas choices were decodable from a confined set of brain structures, their outcomes were decodable from nearly all cortical and subcortical structures. In addition, signals related to both reinforcements and punishments were recovered reliably in many areas and displayed patterns not consistent with salience-based explanations. Thus, reinforcement and punishment might play global modulatory roles in the entire brain. PMID- 21982378 TI - Olfactory predictive codes and stimulus templates in piriform cortex. AB - Neuroscientific models of sensory perception suggest that the brain utilizes predictive codes in advance of a stimulus encounter, enabling organisms to infer forthcoming sensory events. However, it is poorly understood how such mechanisms are implemented in the olfactory system. Combining high-resolution functional magnetic resonance imaging with multivariate (pattern-based) analyses, we examined the spatiotemporal evolution of odor perception in the human brain during an olfactory search task. Ensemble activity patterns in anterior piriform cortex (APC) and orbitofrontal cortex (OFC) reflected the attended odor target both before and after stimulus onset. In contrast, prestimulus ensemble representations of the odor target in posterior piriform cortex (PPC) gave way to poststimulus representations of the odor itself. Critically, the robustness of target-related patterns in PPC predicted subsequent behavioral performance. Our findings directly show that the brain generates predictive templates or "search images" in PPC, with physical correspondence to odor-specific pattern representations, to augment olfactory perception. PMID- 21982379 TI - Different modes of state transitions determine pattern in the Phosphatidylinositide-Actin system. AB - BACKGROUND: In a motile polarized cell the actin system is differentiated to allow protrusion at the front and retraction at the tail. This differentiation is linked to the phosphoinositide pattern in the plasma membrane. In the highly motile Dictyostelium cells studied here, the front is dominated by PI3-kinases producing PI(3,4,5)tris-phosphate (PIP3), the tail by the PI3-phosphatase PTEN that hydrolyses PIP3 to PI(4,5)bis-phosphate. To study de-novo cell polarization, we first depolymerized actin and subsequently recorded the spontaneous reorganization of actin patterns in relation to PTEN. RESULTS: In a transient stage of recovery from depolymerization, symmetric actin patterns alternate periodically with asymmetric ones. The switches to asymmetry coincide with the unilateral membrane-binding of PTEN. The modes of state transitions in the actin and PTEN systems differ. Transitions in the actin system propagate as waves that are initiated at single sites by the amplification of spontaneous fluctuations. In PTEN-null cells, these waves still propagate with normal speed but loose their regular periodicity. Membrane-binding of PTEN is induced at the border of a coherent PTEN-rich area in the form of expanding and regressing gradients. CONCLUSIONS: The state transitions in actin organization and the reversible transition from cytoplasmic to membrane-bound PTEN are synchronized but their patterns differ. The transitions in actin organization are independent of PTEN, but when PTEN is present, they are coupled to periodic changes in the membrane binding of this PIP3-degrading phosphatase. The PTEN oscillations are related to motility patterns of chemotaxing cells. PMID- 21982380 TI - Characterization of differences in calculated and actual measured skin doses to canine limbs during stereotactic radiosurgery using Gafchromic film. AB - Accurate calculation of absorbed dose to the skin, especially the superficial and radiosensitive basal cell layer, is difficult for many reasons including, but not limited to, the build-up effect of megavoltage photons, tangential beam effects, mixed energy scatter from support devices, and dose interpolation caused by a finite resolution calculation matrix. Stereotactic body radiotherapy (SBRT) has been developed as an alternative limb salvage treatment option at Colorado State University Veterinary Teaching Hospital for dogs with extremity bone tumors. Optimal dose delivery to the tumor during SBRT treatment can be limited by uncertainty in skin dose calculation. The aim of this study was to characterize the difference between measured and calculated radiation dose by the Varian Eclipse (Varian Medical Systems, Palo Alto, CA) AAA treatment planning algorithm (for 1-mm, 2-mm, and 5-mm calculation voxel dimensions) as a function of distance from the skin surface. The study used Gafchromic EBT film (International Specialty Products, Wayne, NJ), FilmQA analysis software, a limb phantom constructed from plastic waterTM (fluke Biomedical, Everett, WA) and a canine cadaver forelimb. The limb phantom was exposed to 6-MV treatments consisting of a single-beam, a pair of parallel opposed beams, and a 7-beam coplanar treatment plan. The canine forelimb was exposed to the 7-beam coplanar plan. Radiation dose to the forelimb skin at the surface and at depths of 1.65 mm and 1.35 mm below the skin surface were also measured with the Gafchromic film. The calculation algorithm estimated the dose well at depths beyond buildup for all calculation voxel sizes. The calculation algorithm underestimated the dose in portions of the buildup region of tissue for all comparisons, with the most significant differences observed in the 5-mm calculation voxel and the least difference in the 1-mm voxel. Results indicate a significant difference between measured and calculated data extending to average depths of 2.5 mm, 3.4 mm, and 10 mm for the 1-mm, 2-mm, and 5-mm dimension calculation matrices, respectively. These results emphasize the importance of selecting as small a treatment planning software calculation matrix dimension as is practically possible and of taking a conservative approach for skin treatment planning objectives. One suggested conservative approach is accomplished by defining the skin organ as the outermost 2-3 mm of the body such that the high dose tail of the skin organ dose-volume histogram curve represents dose on the deep side of the skin where the algorithm is more accurate. PMID- 21982381 TI - Rapid generation of long tandem DNA repeat arrays by homologous recombination in yeast to study their function in mammalian genomes. AB - We describe here a method to rapidly convert any desirable DNA fragment, as small as 100 bp, into long tandem DNA arrays up to 140 kb in size that are inserted into a microbe vector. This method includes rolling-circle phi29 amplification (RCA) of the sequence in vitro and assembly of the RCA products in vivo by homologous recombination in the yeast Saccharomyces cerevisiae. The method was successfully used for a functional analysis of centromeric and pericentromeric repeats and construction of new vehicles for gene delivery to mammalian cells. The method may have general application in elucidating the role of tandem repeats in chromosome organization and dynamics. Each cycle of the protocol takes ~ two weeks to complete. PMID- 21982382 TI - Morphological description of the mouthparts of the Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Psyllidae). AB - Scanning (SEM) and transmission (TEM) electron microscopy were used to elucidate the morphology of the rostrum, as well as the mandibular and maxillary stylets of the psyllid Diaphorina citri, vector of phloem-inhabiting bacteria associated with citrus huanglongbing (HLB) disease. D. citri has a cone-shaped rostrum that extends behind the pair of prothoracic coxae. The stylet bundle comprises a pair of mandibular (Md) and maxillary (Mx) stylets with a mean length of 513.3 MUm; when retracted, their proximal portions form a loop and are stored in the crumena (Cr). Serial cross-sections of the rostrum revealed that the mandibles are always projected in front of the maxillary stylets. The two maxillary stylets form the food and salivary canals, with diameters of 0.9 MUm and 0.4 MUm respectively. These two canals merge at the end of the stylets forming a common duct with a length of 4.3 MUm and a mean diameter of 0.9 MUm. The acrostyle, a distinct anatomical structure present in the common duct of aphid maxillary stylets, was not observed by TEM in the ultrathin cross-sections of the common duct (CD) of D. citri. This study provides new information on D. citri mouthparts that may help to understand the feeding behaviour of this important vector of HLB-associated bacteria. PMID- 21982383 TI - Retrospective chart review to assess the relationship between depression and sustained virological response from interferon treatment for hepatitis C virus. AB - BACKGROUND: Hepatitis C virus (HCV) is an infection that, if left untreated, may lead to liver complications and death. Current treatment requires peginterferon alfa (IFN) and ribavirin. Interferon can cause depression and irritability. The treatment goal is sustained virological response (SVR) and the impact of depression on SVR is currently inconclusive. OBJECTIVE: The objective of this study was to compare SVR in patients with and without comorbid depression between different viral genotypes to determine if depressive symptoms impact SVR. METHODS: In this retrospective chart review of HCV-treated patients, the Patient Health Questionnaire-9 (PHQ-9) scale for depression score was recorded to identify patients with depression versus patients without depression. Depression status was compared between SVR and non-SVR groups, as measured at 24 weeks posttreatment completion. Fisher exact or X(2) tests were used to evaluate differences between patients achieving SVR and those that did not. Known predictors of poor response were controlled with possible covariates in a multivariable analysis. RESULTS: A total of 101 patients were enrolled in the study; 74 completed treatment and were included in the analysis. Sixty-five percent (17/26) of patients with depression achieved SVR and 54% (26/48) of patients without depression had SVR. SVR was achieved in 58.1% (43/74) of patients, and genotypes 1, 4 or 6 comprised 58.1% (43/74) of patients. We found 64.9% (48/74) had no depression, 20.3% (15/74) had baseline depression prior to IFN treatment, and 14.8% (11/74) had IFN-treatment-associated depression. The majority of patients were men (59.5%), more than 35 years old (91.9%), and Hispanic (55.4%). When these factors were controlled for, there was no statistical significant relationship between depression and SVR (P = 0.2784). CONCLUSION: In these preliminary results, depression status did not impact SVR in this small, selected population of HCV-infected patients. A larger sample size is needed to achieve sufficient power in this population. PMID- 21982384 TI - Cost-effectiveness of optimizing use of statins in Australia: using outpatient data from the REACH Registry. AB - BACKGROUND: Although few cardiovascular registries report the costs of illness or cost-effectiveness of health interventions, such information is critical to inform the effective and cost-effective management of cardiovascular disease, particularly if drawn from population-based registries, which more accurately reflect clinical practice and follow up patients for much longer than clinical trials. OBJECTIVE: The goal of this study was to estimate the cost-effectiveness of closing the statin "treatment gap" in the secondary prevention of coronary artery disease (CAD) in Australia. METHODS: A decision analysis Markov model was developed with yearly cycles and the health states of alive or dead. Using data from the Australian Reduction of Atherothrombosis for Continued Health Registry, the model compared current statin coverage (82%) in the secondary prevention of CAD (the current group) with a hypothetical situation of 100% coverage (the improved group). The 18% gap was filled with use of generic statins. Data from a recent meta-analysis were used to estimate the benefits of statin use in terms of reducing recurrent cardiovascular events and death. Government reimbursement data from 2011 were used to calculate direct health care costs. The cost of the intervention to improve statin coverage was assumed to be $250 per person. Years of life lived and costs were discounted at 5% annually. All values are given in Australian dollars. RESULTS: Among the 2058 subjects in the current group, the model estimated that there would be 106 nonfatal myocardial infractions, 68 nonfatal strokes, and 275 deaths over 5 years. In the improved group, all of whom took statins, the corresponding numbers were 101, 65, and 259, equating to numbers needed to treat of 426, 639, and 127, respectively. Over the 5 years, there would be 0.018 life-years gained (discounted) at a net cost of $546 (discounted) per person. These equated to an incremental cost-effectiveness ratio of $29,717 per life-year gained. CONCLUSION: The results suggest that for patients with CAD, maximizing coverage with statins, in line with evidence-based recommendations, represents a cost-effective means of secondary prevention. PMID- 21982385 TI - Pharmacotherapy review of chronic pediatric hypertension. AB - BACKGROUND: The number of antihypertensive agents on the market has increased dramatically over the past 20 years. Many of these agents are used to treat children and adolescents with hypertension despite there being relatively limited data available supporting such use. Recent legislation has helped to increase the number of studies conducted in children, but many clinical questions remain unanswered. OBJECTIVE: The goals of this article were to review the currently available antihypertensive agents used in the treatment of pediatric hypertension and to assist clinicians in selecting the most appropriate treatment. METHODS: Searches of MEDLINE and International Pharmaceutical Abstracts through July 2011 were conducted. Search terms used included child, pediatric, hypertension, and the following drugs: captopril, enalapril, lisinopril, fosinopril, losartan, valsartan, irbesartan, candesartan, olmesartan, amlodipine, nifedipine, isradipine, felodipine, propranolol, metoprolol, labetalol, minoxidil, furosemide, spironolactone, chlorothiazide, hydrochlorothiazide, hydralazine, and prazosin. Clinical trial data were reviewed and evaluated and were limited to English-language articles. RESULTS: A total of 45 observational and randomized controlled trials were identified and summarized in this review. The angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and calcium channel antagonists (CCAs) had the strongest data to support their use in pediatric patients. ACE inhibitors and ARBs are preferred agents for children with renal disease and have a favorable safety profile. Many trials, including 2 comparative trials, supported the use of CCAs, particularly amlodipine, in children. CONCLUSIONS: Trials in all 3 classes suggested their efficacy as well as a tolerable adverse-effect profile. More trials in children are needed, particularly with newer antihypertensive agents. Comparative trials of different agents are the most lacking. PMID- 21982386 TI - Pharmacokinetics of prednisolone at steady state in young patients with systemic lupus erythematosus on prednisone therapy: an open-label, single-dose study. AB - BACKGROUND: Current prednisone dosing in the treatment of young patients with childhood-onset systemic lupus erythematosus (cSLE) is largely based on achieving balance between therapeutic efficacy and toxicity, with weight-based dosing a common clinical practice. Despite the widespread use of prednisone, few attempts have been made to improve its clinical dosing regimen, and response to prednisone therapy remains variable. OBJECTIVE: The purpose of this study was to characterize the pharmacokinetic (PK) properties of prednisolone, the metabolite of the prodrug prednisone, in cSLE patients and explore the relationship between PK properties and cSLE disease activity. METHODS: Blood samples were taken 1 hour before the morning prednisone dose and at 20, 40, 60, and 90 minutes, and 2, 3, 4, 6, and 9 hours from 8 patients (ages 12-28 years) after an 8-hour fast. The mean weight-adjusted daily prednisone dose, stable for at least 30 days pre study, was 0.29 mg/kg/d. PK analysis of prednisolone was performed using noncompartmental analysis with WinNonlin. cSLE disease activity was measured using the British Isles Lupus Assessment Group index and Systemic Lupus Erythematosus Disease Activity Index. RESULTS: Mean total prednisolone AUC(0-9), prednisone CL/F at steady state, and half-life were 1094 (range, 467-2404) ng/h/mL, 11 (range, 6.7-13.7) L/hr, and 2.6 (range, 1.3-3.9) hours. Mean total prednisolone AUC(0-9) normalized to prednisone dose by weight was 4361 (range, 1136-9580) ng/h/mL/mg/kg. Mean total prednisolone C(max) normalized to prednisone dose by weight was 1097 (range, 301-2211) ng/mL/mg/kg at 1.84 (range, 0.48-4) hours (T(max)). Patients on prednisone had interindividual variability in prednisolone AUC(0-9) (61% CV) and dose-adjusted AUC(0-9) (58% CV). CONCLUSIONS: Interindividual variability in systemic exposure to prednisolone in cSLE patients was observed. PMID- 21982387 TI - Fractures around the lateral cortical hinge after a medial opening-wedge high tibial osteotomy: a new classification of lateral hinge fracture. AB - PURPOSE: The purpose of this study was to determine the frequency of lateral hinge fractures after opening-wedge high tibial osteotomy and investigate the patterns of fracture and their clinical outcome. METHODS: We analyzed 104 knees in 93 patients with a mean age of 68 +/- 7 years. Of the knees, 74 were diagnosed as having primary osteoarthritis and 30 with osteonecrosis. The mean follow-up period was 41 months. Lateral hinge fractures were classified as follows: type I, the fracture reaches just proximal to or within the tibiofibular joint; type II, the fracture reaches the distal portion of the proximal tibiofibular joint; and type III, a lateral plateau fracture. A standard postoperative rehabilitation protocol was used for type I fractures, 3 of 5 patients with type II fractures were treated with non-weight bearing, and type III fractures were treated with non-weight bearing until visible callus formation. RESULTS: The Knee Society scores for the knee and for function showed improvement from 49 +/- 11 to 91 +/- 7.7 points and from 62 +/- 13 to 95 +/- 8.2 points, respectively. Lateral cortex fractures were observed in 26 knees (25%): 19 type I, 5 type II, and 2 type III. In the type II fracture group, 2 of 5 patients were judged to have a delayed bone union. There were 2 cases of infection (2%) and 1 case of traumatic neuroma (1%) but no instances of implant failure, nonunion, or deep vein thrombosis among our patient cohort. CONCLUSIONS: High tibial osteotomy patients treated with a combination of TomoFix (Synthes, Bettlach, Switzerland) and bone substitute were able to walk with full weight bearing 2 weeks after surgery. No complications were seen in 19 patients with type I fractures. Of 5 patients with type II fractures, 2 had delayed unions with a correction loss of 3 degrees and 7 degrees , respectively. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 21982388 TI - An anatomic study of the posterior septum of the knee. AB - PURPOSE: To evaluate the posterior septum of the knee and determine the presence of a safe zone that could be removed, without significant damage to blood vessels and nerves. METHODS: Nineteen fresh unpaired adult human cadaveric knees, with no macroscopic degenerative or traumatic changes, were used in this study. Microscopic evaluation was performed by analysis of H&E, CD-34, and S-100 staining. RESULTS: The posterior septum of the knee is rich in type II and type IV mechanoreceptors and blood vessels. The superior half has a greater number of blood vessels (21.52 +/- 6.36 v 12.05 +/- 4.1, P < .001), higher-caliber vessels (2.2 +/- 0.89 MUm v 1.41 +/- 0.45 MUm, P < .006), and a greater number of mechanoreceptors per field (type II, 1.8 +/- 1.8 v 0.42 +/- 1, P = .04; type IV, 22.6 +/- 14 v 14.5 +/- 9.4, P = .04) than the inferior half of the septum. CONCLUSIONS: This study has shown that the posterior septum of the knee is highly vascularized and has a great number of type II and IV mechanoreceptors. The presence of these structures is significantly higher in the superior half of the septum. CLINICAL RELEVANCE: If debridement of the posterior septum is necessary, it should be done at the inferior aspect so that a greater number of blood vessels and mechanoreceptors can be preserved. PMID- 21982389 TI - Arthroscopic suture anchor repair versus pullout suture repair in posterior root tear of the medial meniscus: a prospective comparison study. AB - PURPOSE: To evaluate functional and radiographic results of arthroscopic suture anchor repair for posterior root tear of the medial meniscus (PRTMM) and compare with pullout suture repair. METHODS: From December 2006 to August 2008, 51 consecutive patients underwent arthroscopic repair of PRTMM at our hospital. The repair technique was switched over time from pullout suture repair (group 1) to suture anchor repair (group 2). Of the patients, 6 were lost to follow-up, leaving a study population of 45 patients, with 22 menisci (48.9%) in group 1 and 23 (51.1%) menisci in group 2. The mean follow-up duration was 25.9 months (range, 24 to 27 months) in group 1 and 26.8 months (range, 24 to 28 months) in group 2. Compared variables included International Knee Documentation Committee criteria, Kellgren-Lawrence grade, gap distance at PRTMM, structural healing, meniscal extrusion, and cartilage degeneration of the medial femoral condyle. RESULTS: At 2 years postoperatively, both groups showed significant improvements in function (P < .05) and did not show significant differences in Kellgren Lawrence grade (P > .05) compared with preoperatively. On magnetic resonance imaging, the gap distance at PRTMM was 3.2 +/- 1.1 mm in group 1 and 2.9 +/- 0.9 mm in group 2 preoperatively (P > .05). Complete structural healing was seen in 11 cases in group 1 and 12 cases in group 2 (P > .05). Mean meniscal extrusion of 4.3 +/- 0.9 mm (group 1) and 4.1 +/- 1.0 mm (group 2) preoperatively was significantly decreased to 2.1 +/- 1.0 mm (group 1) and 2.2 +/- 0.8 mm (group 2) postoperatively (P < .05). Regardless of repair technique, incompletely healed cases showed progression of cartilage degeneration (4 cases in group 1 and 2 cases in group 2). CONCLUSIONS: For PRTMM, our results show significant functional improvement in both the suture anchor repair and pullout suture repair groups. Reduction of meniscal extrusion seems to be appropriate to preserve its protective role against progression of cartilage degeneration after complete healing at PRTMM. LEVEL OF EVIDENCE: Level III, prospective therapeutic comparative study. PMID- 21982390 TI - Hip arthroscopy for femoroacetabular impingement in patients aged 50 years or older. AB - PURPOSE: The purpose of this study was to investigate outcomes after hip arthroscopy in a consecutive series of patients aged 50 years or older and determine how long patients avoided total hip replacement. METHODS: Between 2006 and 2008, prospectively collected data were retrieved from our database on 153 patients aged 50 years or older undergoing hip arthroscopy for femoroacetabular impingement. Data collected included range of motion, Modified Harris Hip Score (MHHS), Hip Outcome Score (HOS) for activities of daily living, HOS for sports, and Short Form 12 score. Survivors were defined as patients not requiring total hip replacement (THR). Survivorship was analyzed by use of the Kaplan-Meier method. RESULTS: THR was required after the arthroscopic treatment in 20% of patients (31 of 153). At 3 years (with data available in 64 patients), patients with greater than 2 mm of joint space had survivorship of 90% whereas those with 2 mm or less had survivorship of 57% (P = .001). In the patients who did not require THR, the MHHS improved from 58 to 84. The HOS for activities of daily living improved from 66 to 87 (P = .001), and the HOS for sports improved from 42 to 72 (P = .001). The physical component of the Short Form 12 improved from 38 to 49 (P = .001), whereas the mental component did not change (54 preoperatively v 53 postoperatively, P = .53). Median patient satisfaction was 9. CONCLUSIONS: On the basis of early results, patients with greater than 2 mm of joint space can expect improvement over preoperative status in pain and function after hip arthroscopy for femoroacetabular impingement. In patients aged 50 years or older with 2 mm of joint space or less and low preoperative MHHSs, early conversion to THR was seen. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 21982392 TI - Spatial variations of 226Ra, 228Ra, 137Cs, and 228Th activities in the southwestern Okhotsk Sea. AB - We collected 14 water column seawater samples in the southwestern Okhotsk Sea and 7 surface samples around the northern area of Hokkaido Island, Northern Japan, and employed low-background gamma-spectrometry with convenient minimal radiochemical processing to determine the activities of (226)Ra (half-life t(1/2)=1600 y), (228)Ra (5.75 y), (137)Cs (30.2 y), and (228)Th (1.91 y) in the samples. Activities of (226)Ra (~2.3 mBq/L), (228)Ra (~0.7 mBq/L), and (137)Cs (~1 mBq/L) of surface waters on the Okhotsk Sea side show notable differences from those on the Japan Sea side (Soya Warm Current Water; SWCW) (~1.5 mBq/L; 1.5 2 mBq/L; 1.4-1.6 mBq/L), indicating their different origins and lateral mixing patterns. All of these nuclides exhibit unique vertical profiles; activities of soluble (226)Ra, (228)Ra, (137)Cs, and reactive (228)Th exhibit small variations from 50 to 500 m depth ((226)Ra, ~2.2 mBq/L; (228)Ra, ~0.4 mBq/L; (137)Cs, ~1 mBq/L; (228)Th, ~0.13 mBq/L). These profiles can be explained by the convective mixing of surface water such as the East Sakhalin Current Water (ESCW) to this layer. PMID- 21982391 TI - Clinical outcome and imaging of arthroscopic single-row and double-row rotator cuff repair: a prospective randomized trial. AB - PURPOSE: The purpose of this study was to compare the clinical and imaging outcomes of single-row and double-row suture anchor fixation in arthroscopic rotator cuff repair with emphasis on analysis of the effect of various tear size on repair integrity. METHODS: Fifty-three patents were randomized to either single-row or double-row rotator cuff repair at the time of surgical intervention. The clinical results were evaluated by applying the UCLA score and the ASES index and assessing muscle strength in abduction and external rotation with a minimum 2-year follow-up. The postoperative rotator cuff integrity was evaluated by magnetic resonance arthrography at 6-month and minimum 2-year follow up. RESULTS: We enrolled 27 patients in the single-row group and 26 patients in the double-row group. Statistically, the UCLA score; the ASES index; and muscle strength were significantly increased in both groups after surgery, but there was no significant difference between the 2 groups. At minimum 2-year follow-up, intact rotator cuffs were found in 17 patients in the single-row group and 20 in the double-row group, based on magnetic resonance arthrography results. Overall, there was no significant difference in postoperative structural integrity between the 2 groups at 6-month and 2-year follow-up. In patients with tear size larger than 3 cm, the muscle strength of the shoulder was significantly better in the double-row group. For the final imaging results, regardless of the tear size, there was no difference between the single-row and double-row groups. CONCLUSIONS: Arthroscopic rotator cuff repair with double-row fixation showed better shoulder strength in patients with larger tear size (>3 cm) in comparison with single-row fixation. However, the imaging results showed no significant difference in cuff integrity in both groups in patients with any tear size at 6 month and minimum 2-year follow-up. LEVEL OF EVIDENCE: Level II, lesser-quality randomized control trial. PMID- 21982393 TI - Social and ethical issues in environmental remediation projects. AB - The contamination of environments with radionuclides can give rise to consequences that encompass far more than health risks from exposure to radiation. As experience from Chernobyl demonstrated, both the accident and remediation measures can have serious social and economic consequences. This paper presents a review of some of these issues, including their ethical relevance, and presents a check-list of socio-ethical aspects of remediation measures. The paper concludes with an overview of social remediation measures, encompassing actions that are directed towards benefits other than dose reduction (e.g., local food monitoring stations or medical check-up), or measures that require social rather than technical implementation (e.g. information centres, stakeholder dialogue). PMID- 21982394 TI - Identification and synthesis of by-products found in 4-methylthioamphetamine (4 MTA) produced by the Leuckart method. AB - The synthesis of the designer drug 4-methylthioamphetamine (4-MTA) has been carried out using the well-known Leuckart reaction in four versions. The treatment of 4-methylthiophenylacetone with formamide, mixture of formamide/formic acid, ammonium formate, and mixture of ammonium formate and formic acid followed by acid hydrolysis brought about the formation of 4-MTA contaminated with a number of impurities. The gas chromatography mass spectrometry (GC-MS) analysis of the reaction mixtures allowed identification of the most prominent impurities, such as diasteromers of N,N-di-[beta-(4 methylthiophenyl)isopropyl]amine, N,N-di-[beta-(4 methylthiophenyl)isopropyl]methylamine, N,N-di-[beta-(4 methylthiophenyl)isopropyl]formamide, the Schiff bases derived from 4-MTA and 4 methylbenzaldehyde (benzaldimine) and 4-methylthiophenylacetone (ketimine) as well as some heterocycles: 4-methyl-5-(4'-methylthiophenyl)pyrimidine, 4-(4' methylthiobenzyl)pyrimidine, 2,6-dimethyl-3,5-di-(4'-methylthiophenyl)pyridine, 2,4-dimethyl-3,5-di-(4'-methylthiophenyl)pyridine. The correctness of identification was confirmed by independent synthesis of these compounds. Each synthesized reference compound was characterized by means of MS, (1)H and (13)C NMR, and IR methods. The stereochemistry of (RR/SS) diasteromer of N,N-di-[beta (4-methylthiophenyl)isopropyl]amine was confirmed by a crystallographic method. PMID- 21982396 TI - The role of different methanogen groups evaluated by Real-Time qPCR as high efficiency bioindicators of wet anaerobic co-digestion of organic waste. AB - Methanogen populations and their domains are poorly understood; however, in recent years, research on this topic has emerged. The relevance of this field has also been enhanced by the growing economic interest in methanogen skills, particularly the production of methane from organic substrates. Management attention turned to anaerobic wastes digestion because the volume and environmental impact reductions. Methanogenesis is the biochemically limiting step of the process and the industrially interesting phase because it connects to the amount of biogas production. For this reason, several studies have evaluated the structure of methanogen communities during this process. Currently, it is clear that the methanogen load and diversity depend on the feeding characteristics and the process conditions, but not much data is available. In this study, we apply a Real-Time Polymerase Chain Reaction (RT-PCR) method based on mcrA target to evaluate, by specific probes, some subgroups of methanogens during the mesophilic anaerobic digestion process fed wastewater sludge and organic fraction of the municipal solid waste with two different pre-treatments. The obtained data showed the prevalence of Methanomicrobiales and significantly positive correlation between Methanosarcina and Methanosaetae and the biogas production rate (0.744 p < 0.01 and 0.641 p < 0.05). Methanosarcina detected levels are different during the process after the two pre-treatment of the input materials (T-test p < 0.05). Moreover, a role as diagnostic tool could be suggested in digestion optimisation. PMID- 21982395 TI - Benefits and problems of electronic information exchange as perceived by health care professionals: an interview study. AB - BACKGROUND: Various countries are currently implementing a national electronic patient record (n-EPR). Despite the assumed positive effects of n-EPRs, their overall adoption remains low and meets resistance from health care providers. This study aims to increase our understanding of health care providers' attitude towards the n-EPR, by investigating their perceptions of the benefits and problems of electronic information exchange in health care and the n-EPR in particular. METHODS: The study was conducted in three Dutch health care settings: acute care, diabetes care, and ambulatory mental health care. Two health care organisations were included per setting. Between January and June 2010, interviews were conducted with 17 stakeholders working in these organisations. Relevant themes were deduced by means of thematic qualitative analysis. RESULTS: Health care providers perceived electronic information exchange to promote the efficiency and quality of care. The problems they perceived in electronic information exchange mainly concerned the confidentiality and safety of information exchange and the reliability and quality of patient data. Many problems perceived by health care providers did not specifically apply to the n EPR, but to electronic information exchange in general. CONCLUSIONS: The implementation of the Dutch n-EPR has mainly followed a top-down approach, thereby neglecting the fact that the perceptions and preferences of its users (health care providers) need to be addressed in order to achieve successful implementation. The results of this study provide valuable suggestions about how to promote health care providers' willingness to adopt electronic information exchange, which can be useful for other countries currently implementing an n EPR. Apart from providing information about the benefits and usefulness of electronic information exchange, efforts should be focused on minimising the problems as perceived by health care providers. The safety and confidentiality of electronic information exchange can be improved by developing tools to evaluate the legitimacy of access to electronic records, by increasing health care providers' awareness of the need to be careful when using patient data, and by measures to limit access to sensitive patient data. Improving health care providers' recording behaviour is important to improve the reliability and quality of electronically exchanged patient data. PMID- 21982397 TI - Percussion hemoglobinuria - a novel term for hand trauma-induced mechanical hemolysis: a case report. AB - INTRODUCTION: Extracorpuscular hemolysis caused by mechanical trauma has been well described in relation to lower extremity use, such as in soldiers and runners. Terms such as "march hemoglobinuria", "foot strike hemolysis" and "runners hemoglobinuria" have previously been coined and are easily recalled. Newer cases, however, are being identified in individuals vigorously using their upper extremities, such as drum players who use their hands to strike the instrument. Given the increased recognition of upper extremity-related mechanical hemolysis and hemoglobinuria in drummers, and the use of hand drumming worldwide, we would like introduce a novel term for this condition and call it "percussion hemoglobinuria". CASE PRESENTATION: A 24-year-old Caucasian man presented with reddish brown discoloration of his urine after playing the djembe drum. Urine examination after a rigorous practice session revealed blood on the dipstick, and 0 to 2 red blood cells per high power field microscopically. The urine sample was negative for myoglobulin. Other causes of hemolysis and hematuria were excluded and cessation of drum playing resulted in resolution of his symptoms. CONCLUSIONS: The association of mechanical trauma-induced hemoglobinuria and playing hand percussion instruments is increasingly being recognized. We, however, feel that the true prevalence is higher than what has been previously recorded in the literature. By coining the term "percussion hemoglobinuria" we hope to raise the awareness of screening for upper extremity trauma-induced mechanical hemolysis in the evaluation of a patient with hemoglobinuria. PMID- 21982398 TI - Serum levels of selenium and smoking habits at age 50 influence long term prostate cancer risk; a 34 year ULSAM follow-up. AB - BACKGROUND: Serum selenium level (s-Se) has been associated with prostate cancer (PrCa) risk. We investigated the relation between s-Se, smoking and non-screening detected PrCa and explored if polymorphisms in two DNA repair genes: OGG1 and MnSOD, influenced any effect of s-Se. METHODS: ULSAM, a population based Swedish male cohort (n = 2322) investigated at age 50 for s-Se and s-Se influencing factors: serum cholesterol, erythrocyte sedimentation rate and smoking habits. At age 71 a subcohort, (n = 1005) was genotyped for OGG1 and MnSOD polymorphisms. RESULTS: In a 34-year-follow-up, national registries identified 208 PrCa cases further confirmed in medical records. Participants with s-Se in the upper tertile had a non-significantly lower risk of PrCa. Smokers with s-Se in the two lower tertiles (<=80 MUg/L) experienced a higher cumulative incidence of PrCa than smokers in the high selenium tertile (Hazard Ratio 2.39; 95% CI: 1.09-5.25). A high tertile selenium level in combination with non-wt rs125701 of the OGG1 gene in combination with smoking status or rs4880 related variation of MnSOD gene appeared to protect from PrCa. CONCLUSIONS: S-Se levels and smoking habits influence long-term risk of PrCa. Smoking as a risk factor for PrCa in men with low s-Se is relevant to explore further. Exploratory analyses of variations in OGG1 and MnSOD genes indicate that hypotheses about patterns of exposure to selenium and smoking combined with data on genetic variation in genes involved in DNA repair can be valuable to pursue. PMID- 21982399 TI - Streptococcal tonsillitis as a cause of urticaria: tonsillitis and urticaria. AB - BACKGROUND: The primary role of infections in chronic urticaria (CU) is controversial. We hypothesised that streptococcal tonsillitis (ST) could be a primary cause of CU or acute recurrent urticaria (ARU). METHODS: Retrospective study of 14 outpatients observed between January 2000 and December 2009, with CU/ARU and clinical and/or laboratorial suspicion of an aetiopathogenic link with ST. Clinical history, objective examination and laboratorial study were looked for. Three groups were defined: spontaneous resolution of urticaria, resolution after tonsillectomy, and still symptomatic. RESULTS: In these patients, a causal relationship between ST and urticaria is supported by: markers of streptococcal infection, the perception of a clinical relationship between tonsillitis and urticaria, the decrease of urticaria severity with early antibiotherapy to tonsillitis and urticaria resolution after tonsillectomy. CONCLUSIONS: Our study encourages the investigation of tonsillitis in these otherwise idiopathic patients, especially until young adulthood and even in the absence of any symptoms. PMID- 21982400 TI - Systemic allergic reaction due to intranasal budesonide. PMID- 21982401 TI - Immunomodulatory effects of black seeds and garlic on alloxan-induced Diabetes in albino rat. AB - BACKGROUND: Alteration in the proliferation capacity of leukocytes and in the level of some cytokines, such as TNF-alpha, IL-4 and IL-8 have been suggested to associate with Diabetes mellitus in alloxan-induced diabetic rats given the potential immunomodulatory effects of black seeds and garlic. AIM OF THE WORK: The aim of this study was to test the effects of these agents on the immune cells in alloxan-induced diabetic rats. METHODS: To this end, Diabetes was induced in albino rats by a single intraperitoneal injection of alloxan monohydrate (120mg/kg of body weight). Diabetic rats were then fed normal diet or diet with black seeds or garlic for 28 days. RESULTS: The results showed significant increase in the numbers of monocytes and granulocytes, but with significant decreases in lymphocyte proliferation and the TNF-alpha, interleukin (IL)-4 and IL-8 levels in the diabetic group. Treatment of diabetic rats with black seeds or garlic induced significant amelioration in the numbers of monocytes and granulocytes, with significant increase in lymphocytes numbers and the TNF-alpha, IL-4 and IL-8 levels. CONCLUSIONS: These results indicate the potential beneficial effects of black seeds and garlic as adjuvant treatment during treatment of Diabetes. PMID- 21982402 TI - Prevalence and real clinical impact of Cupressus sempervirens and Juniperus communis sensitisations in Tuscan "Maremma", Italy. AB - OBJECTIVE: The aim was to evaluate the impact of Cupressus sempervirens (Cs) and Juniperus communis (Jc) sensitisations in "Maremma" in southern Tuscany. METHODS: 811 consecutive outpatients (357 F - 57.86%; age: 36.9 +/- 16.6) with suspected allergic respiratory symptoms underwent skin prick tests (SPT) for common allergens and for Cs and Jc. RESULTS: SPT resulted negative in 295 (36.37%) subjects. A Cs/Jc sensitisation was found in 294 (36.25%): 289 (98.3%) were sensitised to Cs whereas 198 (67.34%) to Jc. There was a co-sensitisation between Cs and Jc in 193 (65.6%) subjects. Cs/Jc mono-sensitisation was found in 39 (13.6%) subjects. A higher number (p<0.0001) of Cs/Jc sensitised subjects reported winter (131-44.55%) and spring (124-42.2%) symptoms compared to Cs/Jc non-sensitised and non-allergic subjects. Most Cs/Jc sensitised subjects reported rhinitis and conjunctivitis (p<0.0001), whereas only few reported coughing and asthma (p<0.01). The most frequent co-sensitisation was with grass, olive and other trees in Cs/Jc subjects (p<0.001). Those who reported winter symptoms, likely influenced by Cupressaceae, rhinitis was the main symptom whereas asthma was less frequent. Cs/Jc sensitisation resulted to be a risk factor (OR: 1.73 [CI95% 1.18-2.55]) for rhinitis whereas the probability of being asthmatic was reduced (OR: 0.62 [CI95% 0.44-0.85]). CONCLUSION: The prevalence of Cs/Jc sensitisation is about 36% in "Maremma". However, only in 44% of the patients, Cs/Jc seem to cause typical winter symptoms. Rhinitis is the predominant symptom, whereas asthma is less frequent. Testing Cupressaceae sensitisation using Jc pollen extract, rather than Cs, may result to be less sensitive. PMID- 21982403 TI - [Intermediate-filament-associated diseases]. AB - Intracellular protein filaments intermediate in size between actin filaments and microtubules are composed of a variety of tissue specific proteins. The sequence conservation of the coiled-coil alpha-helical structure responsible for polymerization into individual 10 nm filaments defines a large gene family. Intermediate filaments (IFs) include the nuclear lamins, which are universal in Metazoans, and the cytoplasmic intermediate filaments, which are more varied and form cell type specific networks in animal cells. IFs all share a common tripartite structure consisting of a highly conserved central helical rod domain and variable N-head and C-tail domains. In contrast to actin and tubulin, IFs do not require nucleoside triphosphates such as ATP or GTP for polymerization but they self assemble. According to sequences, the IFs proteins are grouped into seven classes, including five cytoplasmic, one nuclear and one sub-cortical localizations. The search for functions of IFs has led to discoveries of roles in the skin, heart, muscle, liver and brain, in premature aging and of involvement in several degenerative disorders. Mutations in IFs cause or predispose to more than 80 human tissue-specific diseases. Mouse models and gene invalidation have been extremely helpful in eliciting IF role in physiopathology. Besides mechanical role in cell plasticity and stress absorbers, IF functions are related to the capacity to interact with signaling molecules and cell kinases, controlling gene regulatory networks. The reviews herein include a historical perspective about IFs, describe how mutations affect IF structure and assembly properties in desminopathies, inclusion formation in the neurodegenerative Alexander disease, and how they induce multiple disorders in laminopathies. PMID- 21982404 TI - [Laminopathies: one gene, several diseases]. AB - Lamins A and C, encoded by the LMNA gene, are nuclear proteins expressed in all post-mitotic cells. Together with B-type lamins, they form a meshwork of proteins beneath the inner nuclear membrane, the lamina, in connection with the cytoskeleton. Lamins A/C also interact with chromatin and numerous proteins, including transcription factors. Mutations in LMNA are responsible for more than ten different disorders, commonly called "laminopathies". These diseases affect tissues in a specific (striated muscle, adipose tissue, peripheral nerve) or in a systemic manner (premature ageing syndromes). This wide spectrum of phenotypes is associated to a wide variety of mutations. This large clinical and genetic heterogeneity, unique to the LMNA gene, makes genotype-phenotype relations particularly difficult to establish. However, correlations have been obtained in several cases. Hence, LMNA mutations identified in premature ageing syndromes lead to the accumulation of immature proteins with a toxic effect for cells. Mutations in laminopathies of the adipose tissue mainly localize in the Ig-like domain of the proteins, potentially affecting the interaction with the SREBP-1 transcription factor. In laminopathies of the striated muscles, the mutations are spread throughout the gene. These mutations are thought to induce structural modifications of the proteins, thereby affecting their polymerization into nuclear lamina. Such defect would lead to a mechanical weakness of the nuclear lamina and of the cells, particularly in striated muscles continuously stretching. The exploration of pathophysiological mechanisms of LMNA mutations largely benefits from the numerous mouse models created, which have been widely used to analyze affected molecular pathways and to test putative therapeutic treatments. PMID- 21982405 TI - [Desmin filaments and their disorganization associated with myofibrillar myopathies]. AB - Desmin, the muscle-specific intermediate filament protein, is one of the earliest markers expressed in all muscle tissues during development. It forms a three dimensional scaffold around the myofibril Z-disc and connects the entire contractile apparatus to the subsarcolemmal cytoskeleton, the nuclei and other cytoplasmic organelles. Desmin is essential for tensile strength and muscle integrity. In humans, disorganization of the desmin network is associated with cardiac and/or skeletal myopathies characterized by accumulation of desmin containing aggregates in the cells. Currently, 49 mutations have been identified in desmin gene. The majority of these mutations alter desmin filament assembly process through different molecular mechanisms and also its interaction with its protein partners. Here, we will give an overview of desmin network organization as well as the impact of desmin mutations on this process. Furthermore, we will discuss the different molecular mechanisms implicated in perturbation of the desmin filament assembly process. PMID- 21982406 TI - [Structural plasticity of the adult central nervous system: insights from the neuroendocrine hypothalamus]. AB - Accumulating evidence renders the dogma obsolete according to which the structural organization of the brain would remain essentially stable in adulthood, changing only in response to a need for compensatory processes during increasing age and degeneration. It has indeed become clear from investigations on various models that the adult nervous system can adapt to physiological demands by altering reversibly its synaptic circuits. This potential for structural and functional modifications results not only from the plastic properties of neurons but also from the inherent capacity of the glial cellular components to undergo remodeling as well. This is currently known for astrocytes, the major glial cells in brain which are well-recognized as dynamic partners in the mechanisms of synaptic transmission, and for the tanycytes and pituicytes which contribute to the regulation of neurosecretory processes in neurohemal regions of the hypothalamus. Studies on the neuroendocrine hypothalamus, whose role is central in homeostatic regulations, have gained good insights into the spectacular neuronal-glial rearrangements that may subserve functional plasticity in the adult brain. Following pioneering works on the morphological reorganizations taking place in the hypothalamo-neurohypophyseal system under certain physiological conditions such as dehydration and lactation, studies on the gonadotropic system that orchestrates reproductive functions have re emphasized the dynamic interplay between neurons and glia in brain structural plasticity processes. This review summarizes the major contributions provided by these researches in the field and also addresses the question of the morphological rearrangements that occur on a 24-h basis in the central component of the circadian clock responsible for the temporal aspects of endocrine regulations. Taken together, the reviewed data highlight the close cooperation between neurons and glia in developing strategies for functional adaptation of the brain to the changing conditions of the internal and external environment. PMID- 21982407 TI - Retention rate of Gabapentin in children with intractable epilepsies at 1 year. AB - Gabapentin (GAB) is a newer second-line antiepileptic drug (AED) used in children. This is a multi-centre retrospective observational study of the efficacy, tolerability and retention rate in 105 children, aged 0-17.5 years (mean 10.1) over a 14 year period. The median age of epilepsy onset was 2.5 years (range 0-14.6). 72% started GAB as at least the 3rd AED, with 43% having been withdrawn from at least 2 AEDs. 77% had focal and 52% symptomatic epilepsies. The maintenance doses for GAB ranged 6.0-87.3 mg/kg/day (mean 43.7). The study comprised 157 person-treatment years for GAB. GAB was well tolerated with 55% remaining on treatment beyond 1 year. No serious adverse events were reported whilst on GAB, but 39% reported possibly and probably related adverse events. Seizure improvement (<50% seizure frequency compared to baseline) at more than 12 months of treatment, was reported in 35% of patients starting GAB, including 6% who remained seizure free. The results demonstrated the efficacy and tolerability of GAB in children with difficult to treat epilepsies, and a good response to treatment beyond 12 months, in both focal and generalised epilepsies. PMID- 21982409 TI - Swimming fundamentals: turning performance of leopard sharks (Triakis semifasciata) is predicted by body shape and postural reconfiguration. AB - Turns are essential maneuvers that sharks employ when foraging, feeding, and migrating. How well any individual performs in turning is determined, in part, by the static form and postural reconfiguration of its body. Since the importance of postural reconfiguration in determining turning performance is not well understood, our goal was to examine how body form and posture correlate with turning performance in juvenile leopard sharks, Triakis semifasciata. From videos of sharks turning laterally in yaw, performance was measured as turning radius, turning angle, angular speed of the head, and translational speed of the body along its path. Body form variables included the body's length, mass, width, second moment of area, and mass moment of inertia. Postural variables included body-bending coefficient, body flexion at different longitudinal positions, and lag time between body flexion and turning of the center of rotation. Using step wise linear regression followed by multiple regression, each performance variable was regressed onto three pools of independent variables: (i) all form variables alone, (ii) all postural variables alone, and (iii) a combination of all form and postural variables. From these correlations, it appears that turning performance may be controlled primarily by the magnitude and timing of the flexion of the body. In other words, sharks alter how they turn by changing the pattern in which they bend their bodies; the body acts as a dynamically reconfiguring rudder. PMID- 21982408 TI - Bird terrestrial locomotion as revealed by 3D kinematics. AB - Most birds use at least two modes of locomotion: flying and walking (terrestrial locomotion). Whereas the wings and tail are used for flying, the legs are mainly used for walking. The role of other body segments remains, however, poorly understood. In this study, we examine the kinematics of the head, the trunk, and the legs during terrestrial locomotion in the quail (Coturnix coturnix). Despite the trunk representing about 70% of the total body mass, its function in locomotion has received little scientific interest to date. This prompted us to focus on its role in terrestrial locomotion. We used high-speed video fluoroscopic recordings of quails walking at voluntary speeds on a trackway. Dorso-ventral and lateral views of the motion of the skeletal elements were recorded successively and reconstructed in three dimensions using a novel method based on the temporal synchronisation of both views. An analysis of the trajectories of the body parts and their coordination showed that the trunk plays an important role during walking. Moreover, two sub-systems participate in the gait kinematics: (i) the integrated 3D motion of the trunk and thighs allows for the adjustment of the path of the centre of mass; (ii) the motion of distal limbs transforms the alternating forward motion of the feet into a continuous forward motion at the knee and thus assures propulsion. Finally, head bobbing appears qualitatively synchronised to the movements of the trunk. An important role for the thigh muscles in generating the 3D motion of the trunk is suggested by an analysis of the pelvic anatomy. PMID- 21982410 TI - Peritoneal macrophages are distinct from monocytes and adherent macrophages. AB - OBJECTIVE: Peritoneal macrophages are used in many studies related to atherosclerosis. In situ, they are non-adherent and upon culturing, they adhere and function as scavengers of modified lipoproteins and dead apoptotic cells. They also produce growth factors, suggesting that they may provide life supporting function as well. In this study, we propose that macrophage adherence plays a major role in their function and propose a novel concept that non adherent macrophages are poor scavengers and may delay the process of apoptosis by secretion of growth factors. METHODS AND RESULTS: We analyzed non-adherent and adherent macrophages for changes in receptor expression, growth factor production and function by microarrays, real-time PCR, and western blot analyses. Our results indicate that adherent macrophages have increased expression of scavenger receptors as compared to fresh peritoneal cells. While genes for many growth factors were expressed in both non-adherent and adherent macrophages, the milk fat globule-epidermal growth factor 8 protein (MFG-E8) that recognizes and takes up apoptotic cells was specifically enhanced in non-adherent cells. Furthermore, early apoptotic endothelial cells demonstrated signs of delayed apoptosis when incubated in the presence of peritoneal lavage fluid that was shown to contain MFG-E8. Functional arrays indicated that peritoneal non-adherent macrophages represent a class of macrophages, distinct from either blood monocytes or adherent cultured macrophages. CONCLUSIONS: These results suggest that the adherence status of macrophages may play a major role in their functions. PMID- 21982411 TI - Effect of dalcetrapib, a CETP modulator, on non-cholesterol sterol markers of cholesterol homeostasis in healthy subjects. AB - OBJECTIVE: Subjects with high HDL-C show elevated plasma markers of cholesterol absorption and reduced markers of cholesterol synthesis. We evaluated the effect of dalcetrapib, a cholesteryl ester transfer protein modulator, on markers of cholesterol homeostasis in healthy subjects. METHODS: Dalcetrapib was administered daily with or without ezetimibe in a randomized, open-label, crossover study in 22 healthy subjects over three 7-day periods: dalcetrapib 900 mg, ezetimibe 10mg, dalcetrapib 900 mg plus ezetimibe 10mg. Plasma non cholesterol sterols lathosterol and desmosterol (cholesterol synthesis markers) and campesterol, beta-sitosterol and cholestanol (intestinal cholesterol absorption markers) were measured. A hamster model was used to compare the effect of dalcetrapib and torcetrapib with or without ezetimibe on these markers and determine the effect of dalcetrapib on cholesterol absorption. RESULTS: Dalcetrapib increased campesterol, beta-sitosterol, and cholestanol by 27% (p = 0.001), 32% (p < 0.001), and 12% (p = 0.03), respectively, in man (non cholesterol sterol/cholesterol ratio). Dalcetrapib+ezetimibe reduced campesterol by 11% (p = 0.02); beta-sitosterol and cholestanol were unaffected. Lathosterol and desmosterol were unchanged with dalcetrapib, but both increased with ezetimibe alone (56-148%, p < 0.001) and with dalcetrapib + ezetimibe (32-38%, p < 0.001). In hamsters, dalcetrapib and torcetrapib increased HDL-C by 49% (p = 0.04) and 72% (p = 0.003), respectively. Unlike torcetrapib, dalcetrapib altered cholesterol homeostasis towards increased markers of cholesterol absorption; cholesterol synthesis markers were unaffected by either treatment. Dalcetrapib did not change plasma (3)H-cholesterol level but increased (3)H-cholesterol in plasma HDL vs non-HDL, after oral dosing of labeled cholesterol. CONCLUSION: Dalcetrapib specifically increased markers of cholesterol absorption, most likely reflecting nascent HDL lipidation by intestinal ABCA1, without affecting markers of synthesis. PMID- 21982412 TI - A dietary approach to increase in-stent stenosis and face validity of a rat model for arterial angioplasty and stenting. AB - OBJECTIVE: To expedite the investigation of new devices for inhibiting restenosis, we aimed to develop a modified model of arterial angioplasty and stenting in rats that showed greater face validity than the traditional rat model. METHODS: Carotid arteries from Sprague-Dawley rats fed a normal or an atherogenic diet containing a low dose of cholate underwent balloon pre-dilation followed by placement of a bare metal stent. Vessel patency was followed for 28d using ultrasound. Stented vessels were then harvested and were subjected to histologic analysis. Plasma lipid profiles and biomarkers of endothelial dysfunction, inflammation and thrombosis were assessed. RESULTS: There was significant interaction between stenting injury and the atherogenic diet, leading to higher levels of markers for inflammation, platelet activation, and endothelial dysfunction, as well as neointimal hyperplasia, compared with stented rats on normal chow. There was a significant correlation between plasma IL-6 and TXB(2) in stented rats, a relationship which may have contributed to exaggerated vessel remodeling with increased platelet sensitivity. Compared to normal chow, the atherogenic diet also increased fibrin and proteoglycan deposition near stent struts. CONCLUSIONS: Arterial stenting, in combination with the atherogenic diet, led to exacerbated endothelial dysfunction, inflammation, platelet activation, and vascular remodeling compared with stented rats on normal chow. By reproducing key features of clinical restenosis that are lacking in other rat models, this modified rat model may serve as a valuable screening tool to rapidly evaluate new coatings and devices before moving candidates into expensive, more time-consuming rabbit or porcine models. PMID- 21982413 TI - Growing up is stressful: biophysical laws of morphogenesis. AB - Would it not be nice to understand the rules that govern how a small and round zygote reforms itself into a full blown three-dimensional and structured organism? The past decades have provided us with a wealth of knowledge about molecular mechanisms, intracellular behaviors, and tissue organization. However, we still do not know how to systematically integrate molecular mechanisms into descriptions that operate at larger scales involving higher-order structures such as the actomyosin cell cortex or an entire tissue. For development, it is the biophysical laws by which these structures deform, move, and restructure that are essential for morphogenetic rearrangements at developmental length- and time scales. Recent years have seen the advent of systematic approaches for identifying these laws and ways to determine associated physical behaviors. Here I attempt to paint an intuitive picture of the mechanical concepts that are important for large-scale developmental rearrangements, and I briefly review the technique of laser ablation for measuring associated physical quantities and testing physical models. PMID- 21982414 TI - Spontaneous corneal clearing after Descemet's stripping without endothelial replacement. AB - PURPOSE: To report spontaneous corneal clearing with improved visual acuity and central endothelial cell repopulation after Descemet's stripping without endothelial replacement. DESIGN: Interventional case report. METHODS: A 34-year old woman with bilateral decreased vision secondary to corneal edema from endothelial dysfunction underwent Descemet's stripping endothelial keratoplasty (DSEK) in the right eye and Descemet's stripping only in the left eye. Histopathologic evaluation confirmed a dual diagnosis of Fuchs' endothelial dystrophy and posterior polymorphous membrane dystrophy from Descemet's membrane specimens removed from each eye. After primary graft failure with regraft in the right eye, the second posterior corneal lenticule detached and was removed and not replaced. The cornea cleared, and central endothelial cell repopulation was documented by confocal microscopy. Therefore, Descemet's stripping without endothelial replacement was performed in the left eye. The left cornea also cleared with central endothelial cell repopulation. MAIN OUTCOME MEASURES: Postoperative visual acuity and central endothelial cell repopulation. RESULTS: Endothelial migration after Descemet's stripping alone in the left eye, with probable host endothelial cell repopulation in the right eye. CONCLUSIONS: Endothelial cell migration after Descemet's stripping procedure without insertion of endothelial graft can occur, resulting from host endothelial cell repopulation with corneal clearing and improved visual acuity. PMID- 21982416 TI - Ab interno trabeculectomy versus trabeculectomy for open-angle glaucoma. AB - PURPOSE: To compare the effect of ab interno trabeculectomy with trabeculectomy. DESIGN: Retrospective, cohort study. PARTICIPANTS: A total of 115 patients who underwent ab interno trabeculectomy (study group) compared with 102 patients who underwent trabeculectomy with intraoperative mitomycin as an initial surgical procedure (trabeculectomy group). Inclusion criteria were open-angle glaucoma, age >= 40 years, and uncontrolled on maximally tolerated medical therapy. Exclusion criterion was concurrent surgery. METHODS: Clinical variables were collected from patient medical records. MAIN OUTCOME MEASURES: Intraocular pressure (IOP) and Cox proportional hazard ratio (HR) and Kaplan-Meier survival analyses with failure defined as IOP >21 mmHg or less than 20% reduction below baseline on 2 consecutive follow-up visits after 1 month; IOP <= 5 mmHg on 2 consecutive follow-up visits after 1 month; additional glaucoma surgery; or loss of light perception vision. Secondary outcome measures include number of glaucoma medications and occurrence of complications. RESULTS: Mean follow-up was 27.3 and 25.5 months for the study and trabeculectomy groups, respectively. Intraocular pressure decreased from 28.1 +/- 8.6 mmHg at baseline to 15.9 +/- 4.5 mmHg (43.5% reduction) at month 24 in the study group, and from 26.3 +/- 10.9 mmHg at baseline to 10.2 +/- 4.1 mmHg (61.3% reduction) at month 24 in the trabeculectomy group. The success rates at 2 years were 22.4% and 76.1% in the study and trabeculectomy groups, respectively (P<0.001). Younger age (P = 0.037; adjusted HR, 0.98 per year; 95% confidence interval [CI], 0.97-0.99) and lower baseline IOP (P = 0.016; adjusted HR, 0.96 per 1 mmHg; 95% CI, 0.92-0.99) were significant risk factors for failure in the multivariate analysis of the study group. With the exception of hyphema, the occurrence of postoperative complications was more frequent in the trabeculectomy group (P<0.001). More additional glaucoma procedures were performed after ab interno trabeculectomy (43.5%) than after trabeculectomy (10.8%, P<0.001). CONCLUSIONS: Ab interno trabeculectomy has a lower success rate than trabeculectomy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. PMID- 21982415 TI - Demographic and geographic features of exfoliation glaucoma in 2 United States based prospective cohorts. AB - PURPOSE: To examine prospectively the association between demographic and geographic factors in relation to exfoliation glaucoma (EG) or exfoliation glaucoma suspect (EGS). DESIGN: Prospective cohort study. PARTICIPANTS: Seventy eight thousand nine hundred fifty-five women in the Nurses' Health Study and 41 191 men in the Health Professionals Follow-up Study. METHODS: Female and male health professionals were followed prospectively from 1980 through 2008 and from 1986 through 2008, respectively. Eligible participants were 40 years of age or older, did not have EG or EGS at baseline, and reported undergoing eye examinations during follow-up. Information regarding demographic features, lifetime geographic residence, and potential confounders was collected. During follow-up, 348 EG or EGS cases were confirmed with medical record review. The relative risk of EG or EGS in each cohort was estimated separately and the results were pooled with meta-analysis. MAIN OUTCOME MEASURES: Multivariate rate ratios (MVRRs) of EG or EGS and their 95% confidence intervals (CIs). RESULTS: Exfoliation glaucoma or EGS was strongly age related with subjects 75 years of age or older at 46.22-fold (95% CI, 22.77-93.80) increased risk compared with those between 40 and 55 years of age. Although men were 68% less likely to develop EG or EGS than women (MVRR, 0.32; 95% CI, 0.23-0.46), no predisposition to EG or EGS by ancestry, particularly Scandinavian ancestry, emerged. Compared with a lifetime of living in the northern tier of the continental United States, lifetime residence in the middle geographic tier (MVRR, 0.53; 95% CI, 0.40-0.71) and in the southern geographic tier (MVRR, 0.25; 95% CI, 0.09-0.71) was associated with markedly reduced risks of EG or EGS. CONCLUSIONS: In this mainly white cohort from the United States, increasing age and female gender were significant risk factors for EG or EGS; however, Scandinavian heritage was not. Living in the middle or southern regions of the United States relative to living in the northern region was associated with a reduced risk of EG or EGS. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. PMID- 21982417 TI - Preparation of Pt Ag alloy nanoisland/graphene hybrid composites and its high stability and catalytic activity in methanol electro-oxidation. AB - In this article, PtAg alloy nanoislands/graphene hybrid composites were prepared based on the self-organization of Au@PtAg nanorods on graphene sheets. Graphite oxides (GO) were prepared and separated to individual sheets using Hummer's method. Graphene nano-sheets were prepared by chemical reduction with hydrazine. The prepared PtAg alloy nanomaterial and the hybrid composites with graphene were characterized by SEM, TEM, and zeta potential measurements. It is confirmed that the prepared Au@PtAg alloy nanorods/graphene hybrid composites own good catalytic function for methanol electro-oxidation by cyclic voltammograms measurements, and exhibited higher catalytic activity and more stability than pure Au@Pt nanorods and Au@AgPt alloy nanorods. In conclusion, the prepared PtAg alloy nanoislands/graphene hybrid composites own high stability and catalytic activity in methanol electro-oxidation, so that it is one kind of high-performance catalyst, and has great potential in applications such as methanol fuel cells in near future. PMID- 21982418 TI - The MDCK variety pack: choosing the right strain. AB - The MDCK cell line provides a tractable model for studying protein trafficking, polarity and junctions (tight, adherens, desmosome and gap) in epithelial cells. However, there are many different strains of MDCK cells available, including the parental line, MDCK I, MDCK II, MDCK.1, MDCK.2, superdome and supertube, making it difficult for new researchers to decide which strain to use. Furthermore, there is often inadequate reporting of strain types and where cells were obtained from in the literature. This review aims to provide new researchers with a guide to the different MDCK strains and a directory of where they can be obtained. We also hope to encourage experienced researchers to report the stain and origin of their MDCK cells. PMID- 21982419 TI - Managing resistance in chronic myeloid leukemia. AB - Chronic myeloid leukemia (CML) is a myeloproliferative disorder that affects 5000 new patients per year in the United States. Prior to 10 years ago, durable remission was rare and patients often underwent bone marrow transplantation with substantial morbidity and mortality. Fortunately, CML has been the epicenter of exciting advances in cancer therapy with the discovery of the Bcr-Abl gene fusion and the subsequent development of imatinib mesylate, a small molecule tyrosine kinase inhibitor, to target the kinase activity of the bcr-abl protein product. Despite unprecedented durability for complete hematologic, cytogenetic, and molecular responses seen with front-line imatinib therapy, many patients require alternative therapy because of drug intolerance, suboptimal response, primary resistance, secondary resistance, or progression to advanced phase disease. Further, up to 5% of patients present with advanced disease that does not sustain a durable response to tyrosine kinase inhibitors. Thus, up to one third of CML patients require alternate therapy. Chronic myeloid leukemia has become an exemplary model system for understanding molecular targeting and overcoming mechanisms of drug resistance. This review will discuss potential mechanisms of resistance and ongoing research into novel targets and agents for CML resistant to standard of care. PMID- 21982420 TI - [Dependence: which data to predict the future?]. PMID- 21982421 TI - Cord blood meets its match. PMID- 21982422 TI - Effect of donor-recipient HLA matching at HLA A, B, C, and DRB1 on outcomes after umbilical-cord blood transplantation for leukaemia and myelodysplastic syndrome: a retrospective analysis. AB - BACKGROUND: The importance of matching at the HLA C locus has not been well defined for unrelated umbilical-cord blood transplantation. The selection algorithm for umbilical-cord blood units generally considers intermediate resolution HLA typing at A and B and allele-level typing at DRB1. We aimed to establish the relative importance of additional matching at HLA C. METHODS: We used Cox regression to assess retrospectively the effect of donor-recipient HLA matching on outcomes of single umbilical-cord blood transplantations for leukaemia and myelodysplastic syndrome. Our primary endpoint was transplant related mortality. HLA typing was done with molecular techniques with a minimum of intermediate resolution for HLA A, B, and C, and at the allele-level for DRB1. FINDINGS: The median age of our study population was 10 years (range <1-62) and 552 (69%) of 803 patients were aged 16 years or younger at transplantation. Compared with transplantations matched at HLA A, B, C, and DRB1 (n=69), transplant-related mortality risk was higher after transplantations matched at HLA A, B, and DRB1 and mismatched at HLA C (n=23; HR 3.97, 95% CI 1.27-12.40; p=0.018). Transplant-related mortality risk was also higher after transplantations with a single mismatch at HLA A, B, or DRB1 and mismatched at HLA C (n=234; 1.70, 1.06-2.74; p=0.029) compared with transplantations matched at HLA C with a single mismatch at HLA A, B, or DRB1 (n=127). Assessing the overall effect of HLA disparity on transplant-related mortality, risks were higher with units mismatched at two (n=259; 3.27, 1.42-7.54; p=0.006), three (n=253; 3.34, 1.45-7.71; p=0.005), or four (n=75; 3.51, 1.44-8.58; p=0.006) loci compared with matched units (n=69). INTERPRETATION: Our data suggest that the present strategy for umbilical-cord blood unit selection should be reassessed; matching at HLA C for units that are matched at HLA A, B, or DRB1 or in the presence of a single locus mismatch at HLA A, B, or DRB1 should be included to minimise mortality risks. FUNDING: National Cancer Institute, National Heart Lung and Blood Institute, National Institute for Allergy and Infectious Diseases, Leukemia and Lymphoma Society, US Department of the Navy, Children's Leukemia Research Association, and INSERM. PMID- 21982423 TI - Copy number variants for schizophrenia and related psychotic disorders in Oceanic Palau: risk and transmission in extended pedigrees. AB - BACKGROUND: We report on copy number variants (CNVs) found in Palauan subjects ascertained for schizophrenia and related psychotic disorders in extended pedigrees in Palau. We compare CNVs found in this Oceanic population with those seen in other samples, typically of European ancestry. Assessing CNVs in Palauan extended pedigrees yields insight into the evolution of risk CNVs, such as how they arise, are transmitted, and are lost from populations by stochastic or selective processes, none of which are easily measured from case-control samples. METHODS: DNA samples from 197 subjects affected with schizophrenia and related psychotic disorders, 185 of their relatives, and 159 control subjects were successfully characterized for CNVs using Affymetrix Genomewide Human SNP Array 5.0. RESULTS: Copy number variants thought to be associated with risk for schizophrenia and related disorders also occur in affected individuals in Palau, specifically 15q11.2 and 1q21.1 deletions, partial duplication of IL1RAPL1 (Xp21.3), and chromosome X duplications (Klinefelter's syndrome). Partial duplication within A2BP1 appears to convey an eightfold increased risk in male subjects (95% confidence interval, .8-84.4) but not female subjects (odds ratio = .4, 95% confidence interval, .03-4.9). Affected-only linkage analysis using this variant yields a logarithm of the odds score of 3.5. CONCLUSIONS: This study reveals CNVs that confer risk to schizophrenia and related psychotic disorders in Palau, most of which have been previously observed in samples of European ancestry. Only a few of these CNVs show evidence that they have existed for many generations, consistent with risk variants diminishing reproductive success. PMID- 21982425 TI - Bucindolol, systolic blood pressure, and outcomes in systolic heart failure: a prespecified post hoc analysis of BEST. AB - BACKGROUND: In the Beta-Blocker Evaluation of Survival Trial (BEST), systolic blood pressure (SBP) <= 120 mm Hg was an independent predictor of poor prognosis in ambulatory patients with chronic systolic heart failure (HF). Because SBP is an important predictor of response to beta-blocker therapy, the BEST protocol prespecified a post hoc analysis to determine whether the effect of bucindolol varied by baseline SBP. METHODS: In the BEST, 2706 patients with chronic systolic (left ventricular ejection fraction < 35%) HF and New York Heart Association class III (92%) or IV (8%) symptoms and receiving standard background therapy were randomized to receive either bucindolol (n = 1354) or placebo (n = 1354). Of these, 1751 had SBP <= 120 mm Hg, and 955 had SBP > 120 mm Hg at baseline. RESULTS: Among patients with SBP > 120 mm Hg, all-cause mortality occurred in 28% and 22% of patients receiving placebo and bucindolol, respectively (hazard ratio when bucindolol was compared with placebo, 0.77; 95% confidence interval [CI], 0.59-0.99; P = 0.039). In contrast, among those with SBP <= 120 mm Hg, 36% and 35% of patients in the placebo and bucindolol groups died, respectively (hazard ratio, 0.95; 95% CI, 0.81-1.12; P = 0.541). Hazard ratios (95% CIs; P values) for HF hospitalization associated with bucindolol use were 0.70 (0.56-0.89; P = 0.003) and 0.82 (0.71-0.95; P = 0.008) for patients with SBP > 120 and <= 120 mm Hg, respectively. CONCLUSION: Bucindolol, a nonselective beta-blocker with weak alpha(2)-blocking properties, significantly reduced HF hospitalization in systolic HF patients regardless of baseline SBP. However, bucindolol reduced mortality only in those with SBP > 120 mm Hg. PMID- 21982424 TI - High dimensional endophenotype ranking in the search for major depression risk genes. AB - BACKGROUND: Despite overwhelming evidence that major depression is highly heritable, recent studies have localized only a single depression-related locus reaching genome-wide significance and have yet to identify a causal gene. Focusing on family-based studies of quantitative intermediate phenotypes or endophenotypes, in tandem with studies of unrelated individuals using categorical diagnoses, should improve the likelihood of identifying major depression genes. However, there is currently no empirically derived statistically rigorous method for selecting optimal endophentypes for mental illnesses. Here, we describe the endophenotype ranking value, a new objective index of the genetic utility of endophenotypes for any heritable illness. METHODS: Applying endophenotype ranking value analysis to a high-dimensional set of over 11,000 traits drawn from behavioral/neurocognitive, neuroanatomic, and transcriptomic phenotypic domains, we identified a set of objective endophenotypes for recurrent major depression in a sample of Mexican American individuals (n = 1122) from large randomly selected extended pedigrees. RESULTS: Top-ranked endophenotypes included the Beck Depression Inventory, bilateral ventral diencephalon volume, and expression levels of the RNF123 transcript. To illustrate the utility of endophentypes in this context, each of these traits were utlized along with disease status in bivariate linkage analysis. A genome-wide significant quantitative trait locus was localized on chromsome 4p15 (logarithm of odds = 3.5) exhibiting pleiotropic effects on both the endophenotype (lymphocyte-derived expression levels of the RNF123 gene) and disease risk. CONCLUSIONS: The wider use of quantitative endophenotypes, combined with unbiased methods for selecting among these measures, should spur new insights into the biological mechanisms that influence mental illnesses like major depression. PMID- 21982426 TI - PEGylating a bacteriophage endolysin inhibits its bactericidal activity. AB - Bacteriophage endolysins (lysins) bind to a cell wall substrate and cleave peptidoglycan, resulting in hypotonic lysis of the phage-infected bacteria. When purified lysins are added externally to Gram-positive bacteria they mediate rapid death by the same mechanism. For this reason, novel therapeutic strategies have been developed using such enzybiotics. However, like other proteins introduced into mammalian organisms, they are quickly cleared from systemic circulation. PEGylation has been used successfully to increase the in vivo half-life of many biological molecules and was therefore applied to Cpl-1, a lysin specific for S. pneumoniae. Cysteine-specific PEGylation with either PEG 10K or 40K was achieved on Cpl-1 mutants, each containing an additional cysteine residue at different locations To the best of our knowledge, this is the first report of the PEGylation of bacteriophage lysin. Compared to the native enzyme, none of the PEGylated conjugates retained significant in vitro anti-pneumococcal lytic activity that would have justified further in vivo studies. Since the anti microbial activity of the mutant enzymes used in this study was not affected by the introduction of the cysteine residue, our results implied that the presence of the PEG molecule was responsible for the inhibition. As most endolysins exhibit a similar modular structure, we believe that our work emphasizes the inability to improve the in vivo half-life of this class of enzybiotics using a cysteine-specific PEGylation strategy. PMID- 21982427 TI - PAHs distribution in sediments associated with gas hydrate and oil seepage from the Gulf of Mexico. AB - Six sediment samples collected from the Gulf of Mexico were analyzed. Total concentrations of the PAHs ranged from 52 to 403 ng g(-1) dry weight. The lowest PAH concentration without 5-6 rings PAHs appeared in S-1 sample associated with gas hydrate or gas venting. Moreover, S-1 sample had the lowest organic carbon content with 0.85% and highest reduced sulfur level with 1.21% relative to other samples. And, analysis of the sources of PAHs in S-1 sample indicated that both pyrogenic and petrogenic sources, converserly, while S-8, S-10 and S-11 sample suggested petrogenic origin. The distribution of dibenzothiophene, fluorine and dibenzofuran and the maturity parameters of triaromatic steranes suggested that organic matters in S-1 sample were different from that in S-8, S-10 and S-11 sample. This study suggested that organic geochemical data could help in distinguish the characteristic of sediment associated with gas hydrate or with oil seepage. PMID- 21982429 TI - Early bare-metal stent thrombosis presenting with cardiogenic shock: a case report. AB - INTRODUCTION: Although stents have improved the safety and efficacy of percutaneous coronary interventions, coronary stent thrombosis remains a serious complication. CASE PRESENTATION: We present the case of a 64-year-old Caucasian man from Greece, with symptoms and electrocardiographic findings suggestive of acute inferior myocardial infarction, who complained of chest pain and rapidly developed cardiogenic shock 48 hours after primary percutaneous coronary intervention. CONCLUSION: The most common cause of early bare-metal stent thrombosis is stent malapposition. Intravascular ultrasound is the preferred method to recognize predictors of coronary events that are not detected by angiography. PMID- 21982428 TI - SWASV speciation of Cd, Pb and Cu for the determination of seawater contamination in the area of the Nicole shipwreck (Ancona coast, Central Adriatic Sea). AB - The study reports for the first time on the heavy metal contamination of the waters surrounding a shipwreck lying on the sea floor. Square wave anodic stripping voltammetry has been used for a survey of the total and dissolved Cd, Pb and Cu contents of the seawater at the site of the sinking of the Nicole M/V (Coastal Adriatic Sea, Italy). Results show that the hulk has a considerable impact as regards all three metals in the bottom water, especially for the particulate fraction concentrations, which increased by factors of ~ 9 (Cd), ~ 3 (Pb) and ~ 5 (Cu). The contaminated plume extended downstream for about 2 miles. Much lower contamination was observed for dissolved bottom concentrations; nevertheless Pb (0.56 +/- 0.03 nmol/L) is higher than the Italian legal limits established for 2015 and Cd (0.23 +/- 0.03 nmol/L) is very close the limit of Cd will be exceeded if the hulk is not removed. PMID- 21982431 TI - Amino acids in cat fallopian tube and follicular fluids. AB - Aminograms of tubal and follicular fluids were obtained using fluids collected by aspiratory puncture from six cats. The amino acids were separated and quantified by high-performance liquid chromatography analysis. The serum of the cats was used as control. The three most prevalent amino acids quantified in cat tubal fluid were glycine, glutamic acid, and taurine. Their mean concentrations were 840 MUmol/l (MUm), 808 MUm and 596 MUm, respectively. The three most prevalent amino acids quantified in cat follicular fluid were alanine, glutamine, and taurine. Their mean concentrations were 359 MUm, 351 MUm, and 258 MUm, respectively. This result is consistent with aminograms of tubal fluid previously determined in other mammals. As previously observed in other species and humans, glycine was quantitatively the most abundant and most prevalent free amino acid in cat tubal fluid. The total quantity of amino acids in tubal fluid was similar in cats and other species. However, in contrast with other species studied, hypotaurine was not detected in tubal and follicular fluids of female cats. PMID- 21982430 TI - Factors associated with use of community mental health services by schizophrenia patients using multilevel analysis. AB - BACKGROUND: Persons with schizophrenia and related disorders may be particularly sensitive to a number of determinants of service use, including those related with illness, socio-demographic characteristics and organizational factors. The objective of this study is to identify factors associated with outpatient contacts at community mental health services of patients with schizophrenia or related disorders. METHODS: This cross-sectional study analyzed 1097 patients. The main outcome measure was the total number of outpatient consultations during one year. Independent variables were related to socio-demographic, clinical and use of service factors. Data were collected from clinical records. RESULTS: The multilevel linear regression model explained 46.35% of the variance. Patients with significantly more contacts with ambulatory services were not working and were receiving welfare benefits (p = 0.02), had no formal education (p = 0.02), had a global level of severity of two or three (four being the most severe) (p < 0.001), with one or more inpatient admissions (p < 0.001), and in contact with both types of professional (nurses and psychiatrists) (p < 0.001). The patients with the fewest ambulatory contacts were those with diagnoses of persistent delusional disorders (p = 0.04) and those who were attended by four of the 13 psychiatrists (p < 0.001). CONCLUSIONS: As expected, the variables that explained the use of community service could be viewed as proxies for severity of illness. The most surprising finding, however, was that a group of four psychiatrists was also independently associated with use of ambulatory services by patients with schizophrenia or related disorders. More research is needed to carefully examine how professional support networks interact to affect use of mental health. PMID- 21982432 TI - The effect of oviductal fluid on protein tyrosine phosphorylation in cryopreserved boar spermatozoa differs with the freezing method. AB - Sperm capacitation takes place in the oviduct and protein tyrosine phosphorylation of sperm proteins is a crucial step in capacitation and acquisition of fertilizing potential. Cryopreserved spermatozoa show altered expression of protein tyrosine phosphorylation in the oviduct. The present study compared two freezing methods (conventional-conventional freezing (CF) and simplified-simplified freezing (SF) methods) for their effect on the ability of boar spermatozoa to undergo protein tyrosine phosphorylation in response to oviductal fluid (ODF). Cryopreserved boar-spermatozoa were incubated with pre- and post-ovulatory ODF for 6 h at 38 degrees C under 5% CO(2). Aliquots of sperm samples were taken at hourly intervals and analyzed for kinematics and protein tyrosine phosphorylation. Global protein tyrosine phosphorylation in spermatozoa was measured using flow cytometry and different patterns of phosphorylation were assessed using confocal microscopy. Immediately after thawing, no significant difference was observed in post-thaw sperm motility, velocity and global tyrosine phosphorylation between the two methods of freezing although the freezing method significantly (P < 0.05) influenced the effect of oviductal fluid on these parameters during incubation. While spermatozoa frozen by the CF method showed a significantly higher (P < 0.001) proportion of phosphorylation in response to preovulatory ODF during incubation, spermatozoa frozen by the SF method did not elicit such significant response as there was no significant difference in the proportion of tyrosine phosphorylated spermatozoa between treatments at any given time during incubation. If the CF method was used, the proportion of spermatozoa displaying either tail or full sperm phosphorylation increased in response to both preovulatory (EODF) and postovulatory oviductal fluid. However, if the SF method was used, a significant increase in these patterns was noticed only in the EODF treated group. The present study demonstrates that preovulatory isthmic ODF induce tyrosine phosphorylation in a higher proportion of boar spermatozoa compared to the post-ovulatory fluid and that the method of freezing significantly influences the response of post-thaw spermatozoa to porcine ODF. PMID- 21982433 TI - Neuroprotective iridoid glycosides from Cornus officinalis fruits against glutamate-induced toxicity in HT22 hippocampal cells. AB - The methanolic extract of the fruits of Cornus officinalis S et Z. (Cornaceae) showed the significant neuroprotective activity against glutamate-induced toxicity in HT22 hippocampal cells. Chemical profile of n-BuOH fraction of the methanolic extract of C. officinalis fruits, which showed the most potent activity, was established using HPLC-diode array detector-electrospray-MS (HPLC DAD-ESI-MS). Through bioactivity-guided isolation, five iridoid glycosides including one new compound, 7-O-butylmorroniside (1), loganin (2), morroniside (3), 7R-O-methylmorroniside (4), 7S-O-methylmorroniside (5) were isolated from the n-BuOH fraction. The protective activities of the isolated compounds, themselves, were not statistically significant. However, the hydrolyzed products of compounds 1, 4 and 5 significantly protected glutamate-injured HT22 cells up to 78+/-2.2%, 60+/-3.2% and 59+/-2.5% of non-treated control, respectively. PMID- 21982434 TI - Bioactive components in the fruits of Ziziphus jujuba Mill. against the inflammatory irritant action of Euphorbia plants. AB - Chinese jujube (also known as Chinese date) is the fruit of Ziziphus jujuba Mill. (Rhamnaceae). As a famous folk medicine, it is used as antidote in traditional Chinese formula, Shi Zao Decoction, to relieve the drastic inflammatory irritant nature of Euphorbia species. The irritant activities may cause serious adverse effects in clinical practices. This study aimed to investigate the active components of Z. jujuba through the inhibitory effects on the inflammatory cells activated by Euphorbia kansui and prostratin, a phorbol ester isolated from Euphorbia fischeriana. Peritoneal macrophage of rat and splenic lymphocyte (splenocyte) of mouse were selected to evaluate these actions in vitro. Nitric oxide (NO) release of macrophage and the proliferation of splenocyte were examined through Griess method and MTT assay. TNF-alpha, as an important pro inflammatory cytokines, was detected with enzyme-linked immunosorbent assay (ELISA) method. Six fractions extracted from Z. jujuba were evaluated and fraction F (triterpene acids fraction) was demonstrated to be the most active part, and then, 21 compounds isolated from Z. jujuba were tested at the concentrations range from 1 MUg/ml to 100 MUg/ml. The results show that 7 compounds of them are likely to be active compounds concerning to their pronounced inhibitory action on the activated inflammatory cells. These effects might be helpful to attenuate the irritant action of Euphorbiaceae plants and protect the gastrointestinal tissue from potent inflammatory injury, which should be beneficial to some diseases, like inflammatory bowel disease. PMID- 21982435 TI - Anti-metastatic effects of ginsenoside Rd via inactivation of MAPK signaling and induction of focal adhesion formation. AB - Ginsenoside Rd is a protopanaxadiol-type ginsenoside found in ginseng and is the active ingredient in several Oriental herbal medicines. We investigated the effects of ginsenoside Rd on tumor invasion and metastasis in the human hepatocellular carcinoma HepG2 and its possible mechanism of action. HepG2 cells were treated with ginsenoside Rd at different concentrations. Scratch wound and Boyden chamber assays were used to determine the effects of ginsenoside Rd on the migration and invasiveness of HepG2 cells, respectively. The molecular mechanisms by which ginsenoside Rd inhibited the invasion and migration of HepG2 cells were investigated by RT-PCR, Western blotting, gelatin zymography, promoter assay, and treatment with inhibitors of MAPK signaling. Immunofluorescence analysis was conducted to evaluate the effect of ginsenoside Rd on focal adhesion formation in HepG2 cells. Treatment with ginsenoside Rd dose- and time-dependently inhibited the migration and invasion of HepG2 cells. It achieved this by reducing the expression of MMP-1, MMP-2, and MMP-7, by blocking MAPK signaling by inhibiting the phosphorylation of ERK and p38 MAPK, by inhibition of AP-1 activation, and by inducing focal adhesion formation and modulating vinculin localization and expression. Treatment of HepG2 cells with ginsenoside Rd significantly inhibited metastasis, most likely by blocking MMP activation and MAPK signaling pathways involved in cancer cell migration. These findings may be useful for the development of novel chemotherapeutic agents for the treatment of malignant cancers. PMID- 21982436 TI - Contribution of flavonoids and catechol to the reduction of ICAM-1 expression in endothelial cells by a standardised Willow bark extract. AB - INTRODUCTION: A quantified aqueous Willow bark extract (STW 33-I) was tested concerning its inhibitory activity on TNF-alpha induced ICAM-1 expression in human microvascular endothelial cells (HMEC-1) and further fractionated to isolate the active compounds. RESULTS: At 50 MUg/ml the extract, which had been prepared from Salix purpurea L., decreased ICAM-1 expression to 40% compared to control cells without showing cytotoxic effects. Further liquid-liquid partition revealed an ethyl acetate phase with potent reduction of ICAM-1 expression to 40% at 8 MUg/ml. This fraction was comprehensively characterised by the isolation of flavanone aglyca and their corresponding glycosides, chalcone glycosides, salicin derivatives, cyclohexane-1,2-diol glycosides, catechol and trans-p-coumaric acid. All compounds were investigated for their activity on TNF-alpha induced ICAM-1 expression. The flavonoid and chalcone glycosides were not active up to 50 MUM, whereas catechol and eriodictyol at the same concentration showed a significant reduction of ICAM-1 expression to 50% of control. Interestingly, other isolated flavanone aglyca like taxifolin, dihydrokaempferol and naringenin showed only weak or moderate inhibitory activity. Eriodictyol was a minor compound in the extract, whereas the catechol content in the extract (without excipients) reached 2.3%, determined by HPLC. One of the isolated cyclohexan-1,2-diol glucosides, 6' O-4-hydroxybenzoyl-grandidentin, is a new natural compound. CONCLUSION: As catechol is quantitatively important in Willow bark extracts it can be concluded from the in vitro data that not only flavonoids and salicin derivatives, but also catechol can probably contribute to the anti-inflammatory activity of Willow bark extracts. PMID- 21982437 TI - Rooibos (Aspalathus linearis) offers cardiac protection against ischaemia/reperfusion in the isolated perfused rat heart. AB - Rooibos, a unique South African herbal tea, is known to be an important source of unique polyphenolic compounds. In the present study we have quantified the main polyphenolic compounds in both fermented/traditional and unfermented/"green" rooibos (Aspalathus linearis) and evaluated its cardioprotective effects against ischaemia/reperfusion injury. Male Wistar rats consumed aqueous rooibos and green tea (Camellia sinensis) extracts (2%, w/v) for 7 weeks before their hearts were rapidly excised and perfused in a working heart perfusion apparatus. The results showed that the rooibos supplemented hearts significantly improved aortic output recovery after reperfusion when compared to the green tea supplemented hearts. Additionally, we showed that the rooibos extracts, containing the highest amount of flavonols, significantly decreased the level of cleaved caspase-3 and PARP, both pro-apoptotic proteins, during reperfusion when compared to green tea. Green tea supplementation increased phosphorylation of total PKB/Akt, Akt (threonine 308) and Akt (serine 473). The rooibos extracts did not cause significant change in the levels of the pro-survival PKB/Akt (threonine 308 and serinet 473). The GSH/GSSG ratio in the hearts of the green tea supplemented group was significantly (p<0.05) lower when compared to RF (37.78+/-28.63), RU (33.20+/ 4.13) and C (45.50+/-14.96). The results clearly demonstrate the cardio protective properties of aqueous rooibos extracts via the inhibition of apoptosis which can possibly be related to the flavonol content of this unique South African herbal tea. PMID- 21982438 TI - Endometriosis: a crosstalk between epidermal growth factor (EGF) gene polymorphism and telomerase activity? PMID- 21982439 TI - Diagnosis of peritoneal tuberculosis: random involvement of gynecologists. PMID- 21982441 TI - XRCC4 controls nuclear import and distribution of Ligase IV and exchanges faster at damaged DNA in complex with Ligase IV. AB - Non-homologous end-joining (NHEJ) is one major pathway for the repair of double stranded DNA breaks in mammals. Following break recognition, alignment and processing, broken DNA ends are finally rejoined by the essential DNA Ligase IV. In the cell, Ligase IV is unable to function without its constitutive interaction partner XRCC4 and becomes unstable when it is missing, and it has been assumed that XRCC4 may also be required for recruitment of Ligase IV to repair sites. To investigate the function of complex formation between both proteins directly in the living cell, we stably expressed them as bio-fluorescent fusion proteins in human HT-1080 cell clones. Ligase IV or XRCC4 were expressed either alone or both were co-expressed at a roughly equimolar ratio. Labelled proteins were overexpressed manifold in comparison to endogenously expressed proteins. We show that over-expressed Ligase IV was only partially imported into the nucleus and showed a diffuse distribution there, whereas XRCC4 expressed alone was entirely nuclear with a distinct exclusion from nucleoli. When Ligase IV was co-expressed with XRCC4, both proteins formed the natural complex, and Ligase IV was not only efficiently imported but also resembled the sub-nuclear distribution of XRCC4. In addition, Ligase IV, when in complex with XRCC4, acquired a delayed nuclear reimport after mitotic cell division of XRCC4. We further determined by photobleaching the kinetics with which the proteins exchange at UVA laser irradiated nuclear sites between damage-bound and diffusing states. We found that the dynamic exchange rate of the Ligase IV/XRCC4 complex at micro-irradiated sites was faster than that of XRCC4 expressed alone. In summary, our findings demonstrate a novel function of XRCC4 in controlling nuclear import and sub nuclear distribution of Ligase IV, and they suggest that XRCC4 modulates the dynamic interaction of the Ligase IV/XRCC4 complex with the NHEJ machinery at double-stranded DNA breaks. PMID- 21982442 TI - Srs2 enables checkpoint recovery by promoting disassembly of DNA damage foci from chromatin. AB - Following DNA repair, checkpoint signalling must be abated to resume cell cycling in a phenomenon known as checkpoint recovery. Although a number of genes have been implicated in the recovery process, it is still unknown whether checkpoint recovery is caused by a signalling network activated by DNA repair or whether it is the result of the loss of DNA structures that elicit the checkpoint. Here we show that checkpoint recovery can be uncoupled from bulk chromosome DNA repair if single-stranded (ss) DNA persists. This situation occurs in cells that are deficient in the Srs2 helicase, a protein that antagonizes Rad51. We report that srs2Delta cells fail to eliminate Ddc2 and RPA subnuclear foci following bulk chromosome repair due to the persistence of ssDNA. In contrast to cells with DNA double-strand breaks that remain unrepaired, srs2Delta cells remove the 9-1-1 checkpoint clamp from chromatin after repair. However, despite the loss of the 9 1-1 clamp, Dpb11 remains associated with chromatin to promote checkpoint activity. Our work indicates that Srs2 promotes checkpoint recovery by removing Rad51 after DNA repair. A failure to remove Rad51 causes persistence of ssDNA and the checkpoint signal. Therefore, we conclude that cells initiate recovery when the DNA structures that elicit the checkpoint are eliminated. PMID- 21982444 TI - Quantitative analysis of fatty-acid-based biofuels produced by wild-type and genetically engineered cyanobacteria by gas chromatography-mass spectrometry. AB - Simple and rapid quantitative determination of fatty-acid-based biofuels is greatly important for the study of genetic engineering progress for biofuels production by microalgae. Ideal biofuels produced from biological systems should be chemically similar to petroleum, like fatty-acid-based molecules including free fatty acids, fatty acid methyl esters, fatty acid ethyl esters, fatty alcohols and fatty alkanes. This study founded a gas chromatography-mass spectrometry (GC-MS) method for simultaneous quantification of seven free fatty acids, nine fatty acid methyl esters, five fatty acid ethyl esters, five fatty alcohols and three fatty alkanes produced by wild-type Synechocystis PCC 6803 and its genetically engineered strain. Data obtained from GC-MS analyses were quantified using internal standard peak area comparisons. The linearity, limit of detection (LOD) and precision (RSD) of the method were evaluated. The results demonstrated that fatty-acid-based biofuels can be directly determined by GC-MS without derivation. Therefore, rapid and reliable quantitative analysis of fatty acid-based biofuels produced by wild-type and genetically engineered cyanobacteria can be achieved using the GC-MS method founded in this work. PMID- 21982443 TI - 6-Carboxyfluorescein and structurally similar molecules inhibit DNA binding and repair by O6-alkylguanine DNA alkyltransferase. AB - Human O6-alkylguanine-DNA alkyltransferase (AGT) repairs mutagenic O6 alkylguanine and O4-alkylthymine adducts in single-stranded and duplex DNAs. These activities protect normal cells and tumor cells against drugs that alkylate DNA; drugs that inactivate AGT are under test as chemotherapeutic enhancers. In studies using 6-carboxyfluorescein (FAM)-labeled DNAs, AGT reduced the fluorescence intensity by ~40% at binding saturation, whether the FAM was located at the 5' or the 3' end of the DNA. AGT protected residual fluorescence from quenching, indicating a solute-inaccessible binding site for FAM. Sedimentation equilibrium analyses showed that saturating AGT-stoichiometries were higher with FAM-labeled DNAs than with unlabeled DNAs, suggesting that the FAM provides a protein binding site that is not present in unlabeled DNAs. Additional fluorescence and sedimentation measurements showed that AGT forms a 1:1 complex with free FAM. Active site benzylation experiments and docking calculations support models in which the primary binding site is located in or near the active site of the enzyme. Electrophoretic analyses show that FAM inhibits DNA binding (IC50~76MUM) and repair of DNA containing an O6-methylguanine residue (IC50~63MUM). Similar results were obtained with other polycyclic aromatic compounds. These observations demonstrate the existence of a new class of non covalent AGT-inhibitors. After optimization for binding-affinity, members of this class might be useful in cancer chemotherapy. PMID- 21982445 TI - From random sphere packings to regular pillar arrays: effect of the macroscopic confinement on hydrodynamic dispersion. AB - Flow and mass transport in bulk and confined chromatographic supports comprising random packings of solid, spherical particles and hexagonal arrays of solid cylinders (regular pillar arrays) are studied over a wide flow velocity range by a numerical analysis scheme, which includes packing generation by a modified Jodrey-Tory algorithm, three-dimensional flow field calculations by the lattice Boltzmann method, and modeling of advective-diffusive mass transport by a random walk particle-tracking technique. We demonstrate the impact of the confinement and its cross-sectional geometry (circular, quadratic, semicircular) on transient and asymptotic transverse and longitudinal dispersion in random sphere packings, and also address the influence of protocol-dependent packing disorder and the particle-aspect ratio. Plate height curves are analyzed with the Giddings equation to quantify the transcolumn contribution to eddy dispersion. Confined packings are compared with confined arrays under the condition of identical bed porosity, conduit cross-sectional area, and laterally fully equilibrated geometrical wall and corner effects on dispersion. Fluid dispersion in a regular pillar array is stronger affected by the macroscopic confinement and does not resemble eddy dispersion in random sphere packings, because the regular microstructure cannot function as a mechanical mixer like the random morphology. Giddings' coupling theory fails to preserve the nature of transverse dispersion behind the arrays' plate height curves, which approach a linear velocity dependence as transverse dispersion becomes velocity-independent. Upon confinement this pseudo-diffusive behavior can outweigh the performance advantage of the regular over the random morphology. PMID- 21982446 TI - The chromatographic processes in the S-chamber with the counter plate. AB - For the first time the chromatographic processes in the new variant of a S(min) chamber with a counter plate (a S(min)(CP)-chamber) positioned at a small distance above a separating plate have been studied, given the adsorption layers of the both plates (the separating plate and the counter plate) are turned to each other. It should be noted that the features of this method have not been completely studied, only two publications were devoted to the practical using of the S(CP)-chamber. Using of a dry counter plate in the S(min)-chamber having been proposed by us recently leads to the marked increase in the volume of the mobile phase that continuously migrates through the separating plate. Using of the S(min)-chamber with the dry counter plate for separation allows, first, substantially (up to 50%) increasing the value of R(f) (especially, in the range of the small meanings of R(f) (0-0.3)), second, increasing the efficiency of separation by 2.0-2.5 times, and, third, increasing the peak resolution of the method by ~25%. It should be noted that although when separating a mixture in the S(min)(CP)-chamber a slight increase in the experiment duration also occurs (by 20-50% depending on the sizes of the used plate), in all the cases chromatographic characteristics markedly improve (in comparison with separation in the same conditions, but without using of the counter plate). PMID- 21982447 TI - Separation science is the key to successful biopharmaceuticals. AB - The impact of economic change, advances in science, therapy and production processes resulted in considerable growth in the area of biopharmaceuticals. Progress in selection of microorganisms and improvements in cell culture and bioreactors is evidenced by increased yields of the desired products in the complex fermentation mixture. At this stage the downstream process of extraction and purification of the desired biopharmaceutical requires considerable attention in the design and operation of the units used for preparative chromatography. Understanding of the process, optimization of column design and experimental conditions have become critical to the biopharmaceutical industry in order to minimize production costs while satisfying new regulatory requirements. Optimization of the purification of biopharmaceuticals by preparative liquid chromatography including an examination of column preparation and bed properties is the focus of this manuscript. PMID- 21982448 TI - Antibody capture by mixed-mode chromatography: a comprehensive study from determination of optimal purification conditions to identification of contaminating host cell proteins. AB - We evaluated mixed mode chromatography for the capture of recombinant antibodies from CHO cell culture supernatants. We studied PPA HyperCel, HEA HyperCel, MEP HyperCel and Capto adhere resins, which all contain hydrophobic and cationic groups. A microplate approach combined with DoE modeling allowed the exploration of the complex behaviors of these mixed mode resins. Optimal conditions for antibody purification and host cell proteins (HCPs) elimination were determined and then directly up-scaled to laboratory columns. Then we used mass spectrometry to identify the major HCPs potentially coeluted with the antibody. Differences between the four resins in terms of amount, complexity and identity of the HCPs present in the elution fractions were investigated. PMID- 21982449 TI - Fast liquid chromatography: the domination of core-shell and very fine particles. AB - Columns packed with sub-2 MUm totally porous and sub-3 MUm core-shell particles are very widespread nowadays to conduct fast and efficient separations. In order to carry out really fast separations, short (5 cm long) columns are very popular today. The goal of this paper is to review the recent possibilities in fast or "ultra-fast" HPLC by applying short and narrow bore columns packed with modern core-shell and very fine fully porous particles. Efficiency data obtained with these recently commercialized columns from the past few years are collected, discussed and compared in terms of potential separation time and efficiency. The reasons of the success of these columns are presented. This paper also shows that theoretically expected efficiency is sometimes compromised in practical work especially in the case of narrow bore columns. The extra-column dispersion of a given LC system can also dramatically decrease the performance of small columns. It is not possible to utilize the real efficiency of these small columns in spite of their really high intrinsic separation power. PMID- 21982450 TI - Integration of algae cultivation as biodiesel production feedstock with municipal wastewater treatment: strains screening and significance evaluation of environmental factors. AB - The objectives of this study are to find the robust strains for the centrate cultivation system and to evaluate the effect of environmental factors including light intensity, light-dark cycle, and exogenous CO2 concentration on biomass accumulation, wastewater nutrient removal and biodiesel production. The results showed that all 14 algae strains from the genus of Chlorella, Haematococcus, Scenedesmus, Chlamydomonas, and Chloroccum were able to grow on centrate. The highest net biomass accumulation (2.01 g/L) was observed with Chlorella kessleri followed by Chlorella protothecoides (1.31 g/L), and both of them were proved to be capable of mixotrophic growth when cultivated on centrate. Environmental factors had significant effect on algal biomass accumulation, wastewater nutrients removal and biodiesel production. Higher light intensity and exogenous CO2 concentration with longer lighting period promote biomass accumulation, biodiesel production, as well as the removal of chemical oxygen demand and nitrogen, while, lower exogenous CO2 concentration promotes phosphorus removal. PMID- 21982451 TI - Sulphur fate and anaerobic biodegradation potential during co-digestion of seaweed biomass (Ulva sp.) with pig slurry. AB - Seaweed (Ulva sp.) stranded on beaches were utilized as co-substrate for anaerobic digestion of pig slurry in three-month co-digestion tests in pilot scale anaerobic digesters in the laboratory. The methanogenic potential of Ulva sp. was low compared to that of other potential co-substrates available for use by farmers: 148 N m3CH4/t of volatile solids or 19 N m3CH4/t of crude product. When used as a co-substrate with pig manure (48%/52% w/w), Ulva sp. seaweed did not notably disrupt the process of digestion; however, after pilot stabilisation, biogas produced contained 3.5% H2S, making it unsuitable for energy recovery without treatment. Sequentially addition of the sulphate reduction inhibitor, potassium molybdate, to a final concentration of 3mM, temporarily reduced H2S emissions, but was unable to sustain this reduction over the three-month period. According to these pilot tests, the use of seaweed stranded on beaches as co substrate in farm-based biogas plants shows some limitations. PMID- 21982452 TI - Thrombotic risk factors and cardiovascular events after endovascular intervention for peripheral arterial disease. AB - OBJECTIVES: Few data are available on thrombophilic risk factors and clinical outcome in patients undergoing percutaneous transluminal angioplasty (PTA) for peripheral arterial disease (PAD). We investigated the role of homocysteine, fibrinogen, Factor VIII (FVIII), lupus anticoagulant (LAC) and FII G20210A, and FV R506Q (FV Leiden) mutations as prognostic factors in 230 patients who underwent PTA for PAD (Fontaine's stages: IIb through IV; aged 69 +/- 1 years). DESIGN AND METHODS: A prospective study. Major adverse cardiovascular events (MACE) were the composite 'end' point. RESULTS: During the follow-up (24.3 +/- 1.5 months), 96 (41.7%) patients reached the 'end' point. According to Cox regression analysis, diabetes and critical limb ischaemia were predictors of MACE, whereas each single thrombophilic alteration was not. Thrombophilic alterations were more frequent in patients that reached the 'end' point, and the patients with two alterations (hazard ratio (HR) 2.55 confidence interval (CI): 1.20-5.46, p = 0.015) and those with three or more alterations (HR 2.91 CI: 1.31 6.45, p = 0.009) had an increased risk for MACE versus those without alterations. Thrombophilic alterations were not associated with limb loss during the follow up. CONCLUSION: The presence of multiple thrombophilic alterations in patients who underwent PTA for PAD is associated with increased risk of arterial thrombotic events. PMID- 21982453 TI - Hybrid laparoscopic technique for renal artery Takayasu arteritis. AB - OBJECTIVE: To evaluate the feasibility of combined laparoscopic technique for different types of vascular reconstruction in the treatment of Takayasu renal artery stenosis. DESIGN: Retrospective study of seven cases of renal artery stenosis caused by Takayasu arteritis (TA). MATERIALS: Institutional practice and hospitalised patients. All these patients manifested renal arterial hypertension and failed to percutaneous transluminal angioplasty (PTA) treatment. Different types of revascularisation using hybrid laparoscopic technique were applied. METHODS: Laparoscopic renal artery isolation and kidney mobilisation were first performed. Several types of vascular reconstruction were performed as two patients underwent autotransplantation, four patients aortorenal bypass and one splenorenal bypass. For bypass patients, hypogastric artery was harvested by laparoscopic approach while saphenous vein and spleen artery were dissected by conventional opening. Autotransplantation and arterial anastomosis were then performed through an open incision. RESULTS: All procedures were performed successfully without major intraoperative complications. The total operative time was 191 (130-280) min while laparoscopic part was 62 (40-105) min. The mean blood loss was 261 (150-400) ml. Postoperative blood pressure returned to normal in five patients but two others required single-agent antihypertensive medication. Minor complications included lumbar artery injury and flank pain each in one case. The anastomosis was patent in all patients and no re-stenosis occurred during 6-40 months of follow-up. CONCLUSIONS: Hybrid laparoscopic techniques involving renal artery dissection and hypogastric artery harvesting are feasible in surgical treatment of Takayasu renal arteritis. This hybrid surgical technique provides an alternative approach to revascularise the renal circulation, especially for the patients of PTA treatment failure. PMID- 21982454 TI - A phase I trial of PR-104, a pre-prodrug of the bioreductive prodrug PR-104A, given weekly to solid tumour patients. AB - BACKGROUND: The phosphate ester PR-104 is rapidly converted in vivo to the alcohol PR-104A, a nitrogen mustard prodrug that is metabolised to hydroxylamine (PR-104H) and amine (PR-104M) DNA crosslinking agents by one-electron reductases in hypoxic cells and by aldo-keto reductase 1C3 independently of oxygen. In a previous phase I study using a q 3 week schedule of PR-104, the maximum tolerated dose (MTD) was 1100 mg/m2 and fatigue, neutropenic fever and infection were dose limiting. The primary objective of the current study was to determine the dose limiting toxicity (DLT) and MTD of weekly PR-104. METHODS: Patients with advanced solid tumours received PR-104 as a 1-hour intravenous infusion on days 1, 8 and 15 every 28 days with assessment of pharmacokinetics on cycle 1 day 1. Twenty-six patients (pts) were enrolled (16 male/10 female; median age 58 yrs, range 30 to 70 yrs) who had received a median of two prior chemotherapy regimens (range, 0 to 3) for melanoma (8 pts), colorectal or anal cancer (3 pts), NSCLC (3 pts), sarcoma (3 pts), glioblastoma (2 pts), salivary gland tumours (2 pts) or other solid tumours (5 pts). PR-104 was administered at 135 mg/m2 (3 pts), 270 mg/m2 (6 pts), 540 mg/m2 (6 pts), 675 mg/m2 (7 pts) and 900 mg/m2 (4 pts) for a median of two treatment cycles (range, 1 to 7 cycles) and five infusions (range, 1 to 18) per patient. RESULTS: Dose-limiting toxicities (DLTs) during cycle one included grade four thrombocytopenia at 540 mg/m2 (1 of 6 pts) and grade four thrombocytopenia and neutropenia at 900 mg/m2 (2 of 4 pts). At an intermediate dose of 675 mg/m2, there were no DLTs among a total of seven patients given 12 treatment cycles but all experienced moderate to severe (grade 2 to 4) haematological toxicity. Thrombocytopenia was delayed in its onset and nadir, and its recovery was protracted and incomplete in many patients. There were no complete or partial tumour responses. PR-104-induced thrombocytopenia and neutropenia correlated with plasma AUC of PR-104, PR-104A and an oxidative semi mustard metabolite (PR-104S1), but no more strongly than with PR-104 dose-level. There was no significant correlation between plasma AUC for the reduced metabolites and myelotoxicity. CONCLUSIONS: Thrombocytopenia, and to a lesser extent neutropenia, was the DLT of weekly PR-104. The MTD was 675 mg/m2/week. PR 104 given weekly may be a suitable protocol for further clinical evaluation as a short course of treatment with fractionated radiotherapy or haematopoietic stem cell support, as its duration of dosing is restricted by delayed-onset and protracted thrombocytopenia. PMID- 21982455 TI - Inhibitory effect of a tyrosine-fructose Maillard reaction product, 2,4-bis(p hydroxyphenyl)-2-butenal on amyloid-beta generation and inflammatory reactions via inhibition of NF-kappaB and STAT3 activation in cultured astrocytes and microglial BV-2 cells. AB - BACKGROUND: Amyloidogenesis is linked to neuroinflammation. The tyrosine-fructose Maillard reaction product, 2,4-bis(p-hydroxyphenyl)-2-butenal, possesses anti inflammatory properties in cultured macrophages, and in an arthritis animal model. Because astrocytes and microglia are responsible for amyloidogenesis and inflammatory reactions in the brain, we investigated the anti-inflammatory and anti-amyloidogenic effects of 2,4-bis(p-hydroxyphenyl)-2-butenal in lipopolysaccharide (LPS)-stimulated astrocytes and microglial BV-2 cells. METHODS: Cultured astrocytes and microglial BV-2 cells were treated with LPS (1 MUg/ml) for 24 h, in the presence (1, 2, 5 MUM) or absence of 2,4-bis(p hydroxyphenyl)-2-butenal, and harvested. We performed molecular biological analyses to determine the levels of inflammatory and amyloid-related proteins and molecules, cytokines, Abeta, and secretases activity. Nuclear factor-kappa B (NF kappaB) DNA binding activity was determined using gel mobility shift assays. RESULTS: We found that 2,4-bis(p-hydroxyphenyl)-2-butenal (1, 2, 5 MUM) suppresses the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as the production of nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-alpha), and interleukin 1beta (IL-1beta) in LPS (1 MUg/ml)-stimulated astrocytes and microglial BV-2 cells. Further, 2,4-bis(p-hydroxyphenyl)-2-butenal inhibited the transcriptional and DNA binding activity of NF-kappaB--a transcription factor that regulates genes involved in neuroinflammation and amyloidogenesis via inhibition of IkappaB degradation as well as nuclear translocation of p50 and p65. Consistent with the inhibitory effect on inflammatory reactions, 2,4-bis(p-hydroxyphenyl)-2-butenal inhibited LPS-elevated Abeta42 levels through attenuation of beta- and gamma secretase activities. Moreover, studies using signal transducer and activator of transcription 3 (STAT3) siRNA and a pharmacological inhibitor showed that 2,4 bis(p-hydroxyphenyl)-2-butenal inhibits LPS-induced activation of STAT3. CONCLUSIONS: These results indicate that 2,4-bis(p-hydroxyphenyl)-2-butenal inhibits neuroinflammatory reactions and amyloidogenesis through inhibition of NF kappaB and STAT3 activation, and suggest that 2,4-bis(p-hydroxyphenyl)-2-butenal may be useful for the treatment of neuroinflammatory diseases like Alzheimer's disease. PMID- 21982456 TI - Automated clinical reminders for primary care providers in the care of CKD: a small cluster-randomized controlled trial. AB - BACKGROUND: Primary care physicians (PCPs) care for most non-dialysis-dependent patients with chronic kidney disease (CKD). Studies suggest that PCPs may deliver suboptimal CKD care. One means to improve PCP treatment of CKD is clinical decision support systems (CDSSs). STUDY DESIGN: Cluster-randomized controlled trial. SETTING & PARTICIPANTS: 30 PCPs in a university-based outpatient general internal medicine practice and their 248 patients with moderate to advanced CKD who had not been referred to a nephrologist. INTERVENTION: 2 CKD educational sessions were held for PCPs in both arms. The 15 intervention-arm PCPs also received real-time automated electronic medical record alerts for patients with estimated glomerular filtration rates <45 mL/min/1.73 m(2) recommending renal referral and urine albumin quantification if not done within the prior year. OUTCOMES: Primary outcome was referral to a nephrologist; secondary outcomes were albuminuria/proteinuria assessment, CKD documentation, optimal blood pressure (ie, <130/80 mm Hg), and use of renoprotective medications. RESULTS: The intervention and control arms did not differ in renal referrals (9.7% vs 16.5%, respectively; between-group difference, -6.8%; 95% CI, -15.5% to 1.8%; P = 0.1) or proteinuria assessments (39.3% vs 30.1%, respectively; between-group difference, 9.2%; 95% CI, -2.7% to 21.1%; P = 0.1). For intervention and control patients without a baseline proteinuria assessment, 27.7% versus 16.3%, respectively, had one at follow-up (P = 0.06). After controlling for clustering, these findings were largely unchanged and no significant differences were apparent between groups. LIMITATIONS: Small single-center university-based practice, use of a passive CDSS that required PCPs to trigger the electronic order set. CONCLUSIONS: PCPs were willing to partake in a randomized trial of a CDSS to improve outpatient CKD care. Although CDSSs may have potential, larger studies are needed to further explore how best to deploy them to enhance CKD care. PMID- 21982457 TI - Imatinib therapy for non-infection-related type II cryoglobulinemia with membranoproliferative glomerulonephritis. AB - Cryoglobulinemia is a systemic immune complex-mediated vasculitis that can have significant morbidity and mortality. The current treatment for cryoglobulinemia, including chlorambucil, steroids, plasmapheresis, and rituximab, is lacking in terms of efficacy, safety, and relapse rates. Imatinib, a tyrosine kinase inhibitor, has been shown to ameliorate the phenotype and kidney injury in a thymic stromal lymphopoietin transgenic mouse model of cryoglobulinemia. We present a case of type II cryoglobulinemia with severe kidney involvement treated with 400 mg of imatinib administered orally daily, plasmapheresis, and steroids, initially with resolution of symptoms, normalization of creatinine level, and marked improvement in proteinuria and cryocrit. Furthermore, on withdrawal of imatinib therapy, proteinuria, creatinine level, and cryocrit worsened until reinstitution of therapy. After treatment resumption, creatinine level, cryocrit, proteinuria, and symptoms dramatically improved and have remained stable for more than 22 months. PMID- 21982458 TI - fSpatial and temporal dynamics of cellulose degradation and biofilm formation by Caldicellulosiruptor obsidiansis and Clostridium thermocellum. AB - Cellulose degradation is one of the major bottlenecks of a consolidated bioprocess that employs cellulolytic bacterial cells as catalysts to produce biofuels from cellulosic biomass. In this study, we investigated the spatial and temporal dynamics of cellulose degradation by Caldicellulosiruptfor obsidiansis, which does not produce cellulosomes, and Clostridium thermocellum, which does produce cellulosomes. Results showed that the degradation of either regenerated or natural cellulose was synchronized with biofilm formation, a process characterized by the formation and fusion of numerous crater-like depressions on the cellulose surface. In addition, the dynamics of biofilm formation were similar in both bacteria, regardless of cellulosome production. Only the areas of cellulose surface colonized by microbes were significantly degraded, highlighting the essential role of the cellulolytic biofilm in cellulose utilization. After initial attachment, the microbial biofilm structure remained thin, uniform and dense throughout the experiment. A cellular automaton model, constructed under the assumption that the attached cells divide and produce daughter cells that contribute to the hydrolysis of the adjacent cellulose, can largely simulate the observed process of biofilm formation and cellulose degradation. This study presents a model, based on direct observation, correlating cellulolytic biofilm formation with cellulose degradation. PMID- 21982460 TI - Value of modern sonography in the assessment of meniscal lesions. AB - The aim of this prospective study was to assess the accuracy of modern ultrasonography in diagnostic imaging of meniscal tears. One hundred and sixty menisci were evaluated in 80 patients (42 females, 38 males, mean age=36.2 years, range=16-70 years). Inclusion criteria for the study were twofold: clinical suspicion of meniscal injury and clinical indication for arthroscopy. Knee examination was performed with the Voluson 730 Expert ultrasound system (General Electric). After sonographic examination, all patients underwent arthroscopic procedures within 1-4 days. The final diagnosis of meniscal tears was taken from surgical reports. The overall sensitivity, specificity, positive predictive value and negative predictive value of sonographic examination in the assessment of meniscal tears amounted to 85.4%, 85.7%, 67.3% and 94.4%, respectively. The statistical parameters were not statistically different in medial and lateral menisci. Age, sex, body mass index (BMI), weight, physical activity, mechanism on injury, and time lapse from injury did not have a statistically significant impact on the usefulness of ultrasonography. The highest sensitivity (>90%) was obtained in medial menisci and in patients with a BMI>25. The highest specificity (>90%) was obtained in lateral menisci, in patients after twisting injuries, in sports injuries, and in recent injuries (time lapse from the injury <1 month). The positive predictive value (PPV) of sonographic examination was higher than 90% only in recent injuries (<1 month), however, the negative predictive value of ultrasound is high, being less than 90% in males with lesions of lateral menisci and in sequelae of sports injuries. PMID- 21982459 TI - Study of Sylvilagus rabbit TRIM5alpha species-specific domain: how ancient endoviruses could have shaped the antiviral repertoire in Lagomorpha. AB - BACKGROUND: Since the first report of the antiretroviral restriction factor TRIM5alpha in primates, several orthologs in other mammals have been described. Recent studies suggest that leporid retroviruses like RELIK, the first reported endogenous lentivirus ever, may have imposed positive selection in TRIM5alpha orthologs of the European rabbit and European brown hare. Considering that RELIK must already have been present in a common ancestor of the leporid genera Lepus, Sylvilagus and Oryctolagus, we extended the study of evolutionary patterns of TRIM5alpha to other members of the Leporidae family, particularly to the genus Sylvilagus. Therefore, we obtained the TRIM5alpha nucleotide sequences of additional subspecies and species of the three leporid genera. We also compared lagomorph TRIM5alpha deduced protein sequences and established TRIM5alpha gene and TRIM5alpha protein phylogenies. RESULTS: The deduced protein sequence of Iberian hare TRIM5alpha was 89% identical to European rabbit TRIM5alpha, although high divergence was observed at the PRYSPRY v1 region between rabbit and the identified alleles from this hare species (allele 1: 50% divergence; allele 2: 53% divergence). A high identity was expected between the Sylvilagus and Oryctolagus TRIM5alpha proteins and, in fact, the Sylvilagus TRIM5alpha was 91% identical to the Oryctolagus protein. Nevertheless, the PRYSPRY v1 region was only 50% similar between these genera. Selection analysis of Lagomorpha TRIM5alpha proteins identified 25 positively-selected codons, 11 of which are located in the PRYSPRY v1 region, responsible for species specific differences in viral capsid recognition. CONCLUSIONS: By extending Lagomorpha TRIM5alpha studies to an additional genus known to bear RELIK, we verified that the divergent species-specific pattern observed between the Oryctolagus and Lepus PRYSPRY domains is also present in Sylvilagus TRIM5alpha. This work is one of the first known studies that compare the evolution of the antiretroviral restriction factor TRIM5alpha in different mammalian groups, Lagomorpha and Primates. PMID- 21982461 TI - Pulmonary nodules: effect of adaptive statistical iterative reconstruction (ASIR) technique on performance of a computer-aided detection (CAD) system-comparison of performance between different-dose CT scans. AB - PURPOSE: To evaluate the effects of ASIR on CAD system of pulmonary nodules using clinical routine-dose CT and lower-dose CT. MATERIALS AND METHODS: Thirty-five patients (body mass index, 22.17 +/- 4.37 kg/m(2)) were scanned by multidetector row CT with tube currents (clinical routine-dose CT, automatically adjusted mA; lower-dose CT, 10 mA) and X-ray voltage (120 kVp). Each 0.625-mm-thick image was reconstructed at 0%-, 50%-, and 100%-ASIR: 0%-ASIR is reconstructed using only the filtered back-projection algorithm (FBP), while 100%-ASIR is reconstructed using the maximum ASIR and 50%-ASIR implies a blending of 50% FBP and ASIR. CAD output was compared retrospectively with the results of the reference standard which was established using a consensus panel of three radiologists. Data were analyzed using Bonferroni/Dunn's method. Radiation dose was calculated by multiplying dose-length product by conversion coefficient of 0.021. RESULTS: The consensus panel found 265 non-calcified nodules <= 30 mm (ground-glass opacity [GGO], 103; part-solid, 34; and solid, 128). CAD sensitivity was significantly higher at 100%-ASIR [clinical routine-dose CT, 71% (overall), 49% (GGO); lower dose CT, 52% (overall), 67% (solid)] than at 0%-ASIR [clinical routine-dose CT, 54% (overall), 25% (GGO); lower-dose CT, 36% (overall), 50% (solid)] (p<0.001). Mean number of false-positive findings per examination was significantly higher at 100%-ASIR (clinical routine-dose CT, 8.5; lower-dose CT, 6.2) than at 0%-ASIR (clinical routine-dose CT, 4.6; lower-dose CT, 3.5; p<0.001). Effective doses were 10.77 +/- 3.41 mSv in clinical routine-dose CT and 2.67 +/- 0.17 mSv in lower-dose CT. CONCLUSION: CAD sensitivity at 100%-ASIR on lower-dose CT is almost equal to that at 0%-ASIR on clinical routine-dose CT. ASIR can increase CAD sensitivity despite increased false-positive findings. PMID- 21982462 TI - Isolation, culturing and characterization of feeder-independent amniotic fluid stem cells in buffalo (Bubalus bubalis). AB - Heterogeneous amniotic fluid contains various cell types. The aim of this study was to characterize and differentiate some of the key stemness attributes of the amniotic fluid-derived cells in buffalo (Bubalus bubalis). The amniotic fluid (AF) cells were cultured without feeder cells, in DMEM containing 15% FBS, 1% non essential amino acids, 1% penicillin/streptomycin/ampicillin, 1% vitamin solution, and 1% l-glutamine in 5% CO(2) in humidified air at 38.5+/-0.5 degrees C. After 6 days of culture different types of cells viz., star shaped (62.7%), spherical without nucleus (1.9%), spherical with nucleus (26.4%), pentagonal (0.4%), and free floating/rounded cells (8.3%) were observed. Most of the cells started anchorage-dependent growth after day 7 of the culture. Expression of alkaline phosphatase (AP) and Oct-4, Nestin and FGF-5 were observed from the AF cells at different passages. Using species-specific primers, a PCR amplicon of 200, 296 and 210 bp were observed for Oct-4, Nestin and FGF-5, respectively. The cells were found to have a normal karyotype at different passages. These results may contribute towards establishing non-embryonic pluripotent stem cells for various therapeutic and reproductive biotechnological applications in the species. PMID- 21982463 TI - VO(acac)(2)/H(2)O(2)/NaI: a mild and efficient combination for the cleavage of dithioacetal derivatives of sugars. AB - A wide variety of dithioacetal derivatives of sugars can be cleaved easily into the corresponding open-chain aldehydo sugars using an efficient combination of VO(acac)(2)/H(2)O(2)/NaI at 0-5 degrees C. Some of the salient features of this protocol are mild reaction conditions, good yields, short reaction times, easy work-up procedures, and non-involvement of toxic chemicals. PMID- 21982464 TI - A new urinary antigen test score correlates with severity of pneumococcal pneumonia in children. AB - BACKGROUND/PURPOSE: Streptococcus pneumoniae is the most common bacterial cause of community-acquired pneumonia in children. This study was designed to determine whether a newly designed urinary antigen test score correlated with severity of pneumococcal pneumonia in children. METHODS: We recruited 119 children hospitalized with pneumonia diagnosed by positive urinary pneumococcal antigen test at the National Cheng Kung University Hospital from 2002 through 2007. The urinary antigen reactivity score was determined by the rate of the reaction time and intensity of the pneumococcal antigen-antibody band. The children were stratified into three groups according to total score: group I, 8; group II, 5-7; and group III, 2-4. Disease severity was based on clinical presentation and radiological and laboratory findings. RESULTS: Patients in group I had significantly more respiratory distress (p = 0.01), oxygen desaturation (p = 0.04), febrile days (p = 0.03), pulmonary complications (p = 0.01), and bacteremia (p = 0.01), greater requirement for intensive care (p = 0.004), longer hospital stays (p < 0.001), and lower white blood cell counts (p = 0.01) than patients in group II or III. CONCLUSION: A new urinary pneumococcal antigen test score correlated well with the severity of pneumococcal pneumonia in children. It might provide helpful diagnostic and prognostic information. PMID- 21982465 TI - Prospective randomized study of efficacy of 1-day versus 3-day antibiotic prophylaxis for preventing surgical site infection after coronary artery bypass graft. AB - BACKGROUND/PURPOSE: Despite general recommendation of short-course antibiotic prophylaxis, prolonged antibiotic use is still commonly reported in clinical settings. This study compared the efficacy of 1-day versus 3-day antibiotic prophylaxis in preventing surgical site infection (SSI) in patients undergoing coronary artery bypass graft (CABG). METHODS: This prospective, randomized control study was performed in a tertiary-care medical center from June 2002 to April 2004. Patients underwent non-emergency CABG and were randomized into two groups receiving either 1 day or 3 days cefazolin prophylaxis. The SSI rates were compared between the two groups. RESULTS: During the study period, 231 patients were enrolled, 120 in the 1-day group and 111 in the 3-day group. Twenty-two episodes of SSI were observed within 1 month after operation: 13 (10.8%) in the 1 day group and nine (8.1%) in the 3-day group (odds ratio: 1.37; 95% confidence interval: 0.56-3.33; p = 0.48). By logistic regression analysis, 1-day prophylaxis with cefazolin was not associated with higher risk of SSI (adjusted odds ratio: 0.91; 95% confidence interval: 0.32-2.56; p = 0.85). CONCLUSION: Antibiotic prophylaxis for 1 day in CABG surgery was associated with similar rates of postoperative infection compared with antibiotic prophylaxis of 3 days. PMID- 21982466 TI - Predictors for readmission of acute ischemic stroke in Taiwan. AB - BACKGROUND/PURPOSE: Hospital readmission rates are usually higher for stroke than for other chronic conditions. To prevent readmission, effective clinical services and accurate estimates of the absolute readmission rates are required. This study examined the patterns of care received by patients with ischemic stroke, estimated stroke readmission rates, and identified predictors related to readmission in Taiwan. METHODS: A retrospective analysis of the claims database of the Bureau of National Health Insurance in 2004-2007 was performed. This study included ischemic stroke patients who survived hospitalization and whose initial admission occurred in 2006. Time-dependent Cox regression models were developed separately to identify predictors of readmission within 1 month, 6 months, and 1 year after index discharge. RESULTS: We identified 1194 patients from the data set. At the initial stroke, the care provided was almost fully concordant with evidence-based practice guidelines, and the prevalence of antiplatelet therapy was 87.8%. The percentage of patients regularly taking antiplatelet agents within 1 month, 6 months, and 1 year after the index discharge was 65.0%, 18.8%, and 8.0%, respectively. The stroke readmission rates for survivors at 1 month, 6 months, and 1 year after the index discharge were 9.9%, 23.0%, and 30.7%, respectively. Older age, diabetes, longer length of stay for the index admission, and continuous use of antiplatelet agents less than 9 months after the index discharge were all predictors of readmission for acute ischemic stroke. CONCLUSION: Stroke readmissions are not related to receipt of less than optimum or below standard health care during index admission in Taiwan. Additional stroke readmissions in Taiwan might be avoided if more patients used antiplatelet agents for a longer period. PMID- 21982467 TI - Prevalence and psychiatric comorbidity of self-reported electromagnetic field sensitivity in Taiwan: a population-based study. AB - BACKGROUND/PURPOSE: Psychological factors have been implicated in the etiology of idiopathic environmental illness in many studies. Few studies have ever reported psychiatric morbidity among individuals with electromagnetic hypersensitivity. We aimed to estimate the prevalence and identify the associated factors of self reported electromagnetic field sensitivity (SREMFS) in adults of Taiwan. METHODS: A total of 1251 adults selected from a nationwide Computer-Assisted Telephone Interviewing system received a telephone survey about the perception of risk from various environmental agents and their effects on health and well-being. RESULTS: The estimated prevalence of people with SREMFS was 13.3 % (95% confidence interval: 11.2-15.3). People aged >65 years were associated with a lower risk of reporting sensitivity to electromagnetic fields, whereas people with a very poor self-reported health status, those who were unable to work, and those who had psychiatric morbidity were associated with a higher risk of having SREMFS. CONCLUSION: The prevalence of SREMFS in the general population of Taiwan is higher than that reported in western countries. People with psychiatric morbidity are more likely to report sensitivity to electromagnetic fields. The cross sectional design precludes the causal inference of all identified correlates and electromagnetic field sensitivity. PMID- 21982468 TI - Respiratory-inductive-plethysmography-derived flow can be a useful clinical tool to detect patients with obstructive sleep apnea syndrome. AB - BACKGROUND/PURPOSE: Obstructive sleep apnea (OSA) is a common disorder characterized by recurrent episodes of a complete or partial collapse of the upper airway during sleep. The disease is traditionally diagnosed by overnight polysomnography with detection flow limitation by nasal pressure cannulas. The aim of this study was to evaluate the accuracy of flow (X flow) from calibrated respiratory inductive plethysmography. METHODS: We studied 60 male and 26 female patients who came to our sleep center in 2007. All the participants received overnight polysomnography and data were graded blindly and randomly by two experienced technicians. RESULTS: Patients with OSA were predominantly male, with higher body mass index, higher percentage of snorers, and more events of oxygen desaturation and arousal than those without OSA. There was a good correlation of X flow and flow from nasal pressure cannulas, regardless of total apnea-hypopnea, apnea or hypopnea events. The correlation was especially strong in severe OSA patients. The sensitivity and specificity to find OSA (apnea-hypopnea index >=5) from X flow versus standard polysomnography was 98% and 100%, respectively. Positive predictive value was 100% and negative predictive value was 97%. CONCLUSION: X flow could be a good clinical tool to be used instead of flow from nasal pressure cannulas in OSA patients. PMID- 21982469 TI - The allele frequency of two single nucleotide polymorphisms in the von Hippel Lindau (VHL) tumor suppressor gene in the Taiwanese population. AB - BACKGROUND: The von Hippel-Lindau (VHL) tumor suppressor gene located on chromosome 3p25-26 is implicated in VHL disease. Two informative single nucleotide polymorphisms are at positions 19 and 1149 on the nucleotide sequence from Gene Bank NM_000551. In this study we examined the allele frequencies at these two loci in the Taiwanese population and compared the results to those from European ethnic populations. METHODS: The allele frequency was examined in 616 healthy individuals including 301 university students and 315 neonates. Both A/G polymorphisms were investigated using restriction fragment length polymorphism analysis created by restriction enzymes, BsaJ I and Acc I. RESULTS: Among these subjects, the allele frequencies at 19 SNP and 1149 SNP for variant G were 0.130 and 0.133, respectively. And these results were significant differences from those of the Caucasian populations. In addition, 90% of the tested subjects had identical genotypes at these two loci suggesting the existence of nonrandom association of alleles. CONCLUSION: We found that the G allele frequency at these two loci in the Taiwanese population is much lower than that in people from Western countries. This phenomenon may be attributed to ethnic effects. PMID- 21982470 TI - Atrioventricular conduction abnormality and hyperchloremic metabolic acidosis in toluene sniffing. AB - Toluene is an aromatic hydrocarbon with widespread industrial use as an organic solvent. As a result of the euphoric effect and availability of these substances, inhalation of toluene-based products is popular among young adults and children. Chronic or acute exposure is known to cause acid-base and electrolyte disorders, and to be toxic to the nervous and hematopoietic systems. We report a 38-year-old man who suffered from general muscular weakness of all extremities after toluene sniffing, which was complicated with hypokalemic paralysis, atrioventricular conduction abnormality, and normal anion gap hyperchloremic metabolic acidosis. Renal function, serum potassium and acid-base status normalized within 3 days after aggressive potassium chloride and intravenous fluid replacement. Electrocardiography showed regression of first-degree atrioventricular block. Exposure to toluene can lead to cardiac arrhythmias and sudden sniffing death syndrome. Tachyarrhythmia is the classical manifestation of toluene cardiotoxicity. Atrioventricular conduction abnormalities have been rarely mentioned in the literature. Knowledge of the toxicology and medical complications associated with toluene sniffing is essential for clinical management of these patients. PMID- 21982471 TI - Recurrence of nasopharyngeal carcinoma in the parotid region after parotid-gland sparing radiotherapy. AB - This study reported our experience of the clinical characteristics of periparotid recurrence of nasopharyngeal carcinoma (NPC) after parotid-gland-sparing radiotherapy. We retrospectively reviewed the charts of 296 patients with NPC who underwent parotid-gland-sparing radiotherapy at the Tri-Service General Hospital from 1998 to 2008. Eighty-three patients underwent three-dimensional conformal radiotherapy, and 205 patients underwent intensity-modulated radiotherapy; parotid glands were spared bilaterally in all patients. None of these patients had undergone previous radiotherapy or surgical treatment of the head and neck. Disease recurred in a spared parotid gland in three patients (1.04%). Two of these patients had undergone three-dimensional conformal radiotherapy and the third underwent intensity-modulated radiotherapy. All three patients had undergone parotidectomy. Adjuvant radiotherapy or concurrent chemoradiation was administered. One patient died of metastatic disease 26 months after diagnosis of recurrence; the others were well with no evidence of disease at 63 and 6 months after initial recurrence. Periparotid recurrence is an uncommon pattern of locoregional failure after parotid-gland-sparing radiotherapy for NPC. Early diagnosis and aggressive therapy for patients with periparotid recurrence may improve outcomes. PMID- 21982472 TI - Accidental or linked: Noncompaction of the ventricular myocardium combined with severe hypertension and hallux valgus. PMID- 21982473 TI - Teaching medical staff in general hospitals about suicide prevention. PMID- 21982475 TI - The mechanisms of ultra-low dose opioid agonist-antagonist. PMID- 21982477 TI - Insect immune responses to nematode parasites. AB - Host innate immunity plays a central role in detecting and eliminating microbial pathogenic infections in both vertebrate and invertebrate animals. Entomopathogenic or insect pathogenic nematodes are of particular importance for the control of insect pests and vectors of pathogens, while insect-borne nematodes cause serious diseases in humans. Recent work has begun to use the power of insect models to investigate host-nematode interactions and uncover host antiparasitic immune reactions. This review describes recent findings on innate immune evasion strategies of parasitic nematodes and host cellular and humoral responses to the infection. Such information can be used to model diseases caused by human parasitic nematodes and provide clues indicating directions for research into the interplay between vector insects and their invading tropical parasites. PMID- 21982481 TI - Gross hematuria caused by a congenital intrarenal arteriovenous malformation: a case report. AB - INTRODUCTION: We report the case of a woman who presented with gross hematuria and was treated with a percutaneous embolization. CASE PRESENTATION: A 48-year old Caucasian woman presented with gross hematuria, left flank pain, and clot retention. The patient had no history of renal trauma, hypertension, urolithiasis, or recent medical intervention with percutaneous instrumentation. The patient did not report any bleeding disorder and was not taking any medication. Her systolic and diastolic blood pressure values were normal at presentation. The patient had anemia (8 mg/dL) and tachycardia (110 bpm). She underwent color and spectral Doppler sonography, multi-slice computed tomography, and angiography of the kidneys, which showed a renal arteriovenous malformation pole on top of the left kidney. CONCLUSIONS: The feeding artery of the arteriovenous malformation was selectively embolized with a microcatheter introduced using a right transfemoral approach. By using this technique, we stopped the bleeding, preserved renal parenchymal function, and relieved the patient's symptoms. The hemodynamic effects associated with the abnormality were also corrected. PMID- 21982482 TI - Intratemporal complications from acute otitis media in children: 17 cases in two years. AB - BACKGROUND: To describe the clinical features of intratemporal complications of acute otitis media (AOM) in children, a retrospective study was carried out for two years. METHODS: We considered acute mastoiditis, presence of postauricular swelling, erythema and tenderness and anteroinferior displacement of the auricle; labyrinthitis, presence of vestibular symptoms (spontaneous nystagmus and ataxia with or without vomiting; and facial nerve palsy, absence or decreased motility in hemiface. All children underwent otomicroscopy for evidence of coexistent or recent AOM. Cultures were obtained by tympanocentesis and myringotomy, drainage of subperiosteal abscess or from granulation tissue during tympanomastoidectomy. RESULTS: From January 2008 to December 2009, 17 patients fulfilled the entry criteria. Median age: 54.2 months. Of the 17 cases, 30% were infants younger than twelve months and most were boys (70.6%). 8/17 were receiving antimicrobial treatment. Diagnoses included 9/17 (52.9%) acute mastoiditis, 7/17 (41.2%) labyrinthitis and 1/17 (5.9%) facial nerve palsy. Intracranial complications were present in 17.6%. All required intravenous antimicrobial treatment. Myringotomy was performed in 16/17, drainage of subperiosteal abscess in 3/17 and tympanomastoidectomy in 2/17. Bacteriology was positive in 9/17 cases, isolating Streptococcus pyogenes (S. pyogenes) in 44% of patients. Secuelaes: One unilateral sensorineural hearing loss. CONCLUSIONS: Acute mastoiditis is the most common complication. Labyrinthitis was diagnosed in 41.2% of cases. S. pyogenes was prevalent in these serious invasive infections in our area. Associated intracranial complications were present in 17.6% cases. Resolution of AOM complications required surgical procedures in all cases (myringotomy, drainage of subperiosteal abscess or tympanomastoidectomy). PMID- 21982483 TI - Risk of cardiovascular mortality in relation to optimal low-density lipoprotein cholesterol combined with hypertriglyceridemia: is there a difference by gender? AB - PURPOSE: The objectives of the present study were to determine whether an optimal low-density lipoprotein cholesterol (LDL-C) combined with hypertriglyceridemia was associated with cardiovascular disease (CVD) mortality and whether these associations differ by gender. METHODS: A cohort of 2903 U.S. adults aged >=45 years (men) and >=55 years (women) at baseline (1988-1994) was followed through December 2006 for CVD mortality. Baseline data were collected through the Third National Health and Nutrition Examination Survey (NHANES III). The definitions of high LDL-C and high triglycerides (TG) (hypertriglyceridemia) levels were based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines. Cox proportional hazard models were used to estimate the hazard ratio (HR) with 95% confidence interval (CI) of death. RESULTS: After adjusting for age, race/ethnicity, and traditional CVD risk factors, the risk of CVD death was approximately two times as high among women with optimal LDL C/hypertriglyceridemia (2.42, 95% CI = 1.35-4.33) compared to women with optimal LDL-C/normal TG. In contrast, no significant difference was found among men on this comparison. CONCLUSIONS: Judging from this study, hypertriglyceridemia is associated with an increased risk of CVD mortality in women but not in men. The association is independent of abnormal LDL-C effect. PMID- 21982484 TI - Interaction of folate intake and the paraoxonase Q192R polymorphism with risk of incident coronary heart disease and ischemic stroke: the atherosclerosis risk in communities study. AB - PURPOSE: To investigate the potential interaction between folate intake and the paraoxonase 1 (PON1) Q192R polymorphism with the risk of incident coronary heart disease (CHD) and ischemic stroke in the Atherosclerosis Risk in Communities study, a population-based prospective cohort of cardiovascular disease in 15,792 white and African-American subject. METHODS: Race-stratified Cox proportional hazards models were performed to examine the interaction between folate intake and the PON1 Q192R polymorphism. RESULTS: A significant inverse association between folate intake and risk of incident CHD among white subjects was found (hazard rate ratio, 1.30; 95% confidence interval, 1.09-1.56; P = .004; folate intake <=155 MUg vs >=279 MUg, reference group). An interaction effect was observed between the dominant genetic model and folate intake with regards to incident ischemic stroke in white subjects (hazard rate ratio, 0.68; 95% confidence interval, 0.91-0.99; and 1.24 from 1st-4th quartile, respectively; P trend = .05). CONCLUSIONS: There was an interaction between folate intake and PON1 Q192 polymorphism with regard to the risk of ischemic stroke in white subjects. Future studies should investigate the interaction between additional polymorphisms within the PON1 gene and genetic variants in other folate metabolizing genes with folate intake on the risk of incident CHD and stroke. PMID- 21982485 TI - The effect of changing diagnostic algorithms on acute myocardial infarction rates. AB - PURPOSE: Population rates of acute myocardial infarction (AMI) are changing. Consistent case definitions to evaluate these trends and make comparisons are essential. The World Health Organization (WHO) AMI diagnostic algorithm and clinical judgments were the standards for classification. However, in recent years, five new algorithms, to include diagnostic advances, are advocated by professional organizations. This study compares AMI rates derived from six algorithms and the impact of troponins on those rates. METHODS: The authors use the population-based Minnesota Heart Survey hospital data in 1995 and 2001 to compare six published diagnostic algorithms and the impact of troponins. RESULTS: In 1995 differences in AMI rates between algorithms ranged from 281/100,000 to 440/100,000 for men and 98/100,000 to 139/100,000 for women. The use of troponin, a more sensitive biomarker, adds to the differences by increasing eligible cases. Using 2001 data in patients where creatine kinase and troponin were simultaneously measured, a 64% and 95% increase in AMI rates among men and women, respectively, was observed. CONCLUSIONS: Accurate and consistent AMI definitions are crucial for clinical trials, epidemiology and public health research. Demonstrated here is the sensitivity of AMI rates to changing case definitions and the biomarker troponin. PMID- 21982486 TI - Biased standard errors from complex survey analysis: an example from applying ordinary least squares to the national hospital ambulatory medical care survey. AB - PURPOSE: A common research interest is to identify whether there is an increasing or decreasing trend for various health-related conditions over time in national complex surveys. We examined whether standard errors from conventional regression approaches appear accurate for trend analysis of complex surveys. METHODS: We re conducted a trend analysis of the national emergency department visit rate from 1997 through 2007 published recently in JAMA. We compared standard errors from classical weighted least squares (CWLS), generalized estimating equation (GEE), information-weighted least squares (IWLS) regression, and nonparametric bootstrapping. RESULTS: The standard errors of the slope estimates from CWLS regression (0.88 per 1000 person-years) and from GEE regression (0.87 per 1000 person-years) were less than half the standard error from IWLS regression (1.98 per 1000 person-years). Nonparametric bootstrapping replicated the IWLS result. The p-value for trend from CWLS was only .002 and the GEE p-value was .00002, both much smaller than the p-value of .09 from IWLS. CONCLUSIONS: In ecologic time-trend analyses, standard errors from CWLS and GEE can be much too small. For these settings, IWLS provides more reliable inferential statistics. PMID- 21982487 TI - The metabolic syndrome and risk of prostate cancer in Italy. AB - PURPOSE: To provide information on the role of the metabolic syndrome on prostate cancer risk. METHODS: We examined data from a multicentric Italian case-control study. Cases were 1294 patients with incident, histologically confirmed prostate cancer. Controls were 1451 men hospitalized with acute, non-neoplastic conditions. All subjects were younger than 75 years. The metabolic syndrome was defined according to selected indicators of abdominal obesity, hypercholesterolemia, hypertension, and diabetes. We computed multivariate odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression. RESULTS: Considering separate components of the metabolic syndrome, the ORs were 0.98 (95% CI, 0.72-1.34) for diabetes, 1.14 (95% CI, 0.96-1.36) for hypertension, 1.54 (95% CI, 1.26-1.89) for hypercholesterolemia, and 1.02 (95% CI, 0.86-1.21) for abdominal obesity. The OR of prostate cancer was 1.66 (95% CI, 1.22-2.28) in men with metabolic syndrome compared with those without. We found ORs of 1.02 (95% CI, 0.83-1.26) for men with one component of the metabolic syndrome, 1.12 (95% CI, 0.89-1.42) for two, 1.65 (95% CI, 1.15-2.36) for three, and 3.99 (95% CI, 1.03-15.4) for four compared with no components. CONCLUSIONS: The metabolic syndrome was associated with the risk of prostate cancer in this population. PMID- 21982488 TI - Use of antiepileptic medications in pregnancy in relation to risks of birth defects. AB - PURPOSE: To evaluate use of specific antiepileptic drugs (AEDs) in pregnancy in relation to specific birth defects. METHODS: Using data from the National Birth Defects Prevention Study, we assessed use of AEDs and the risk of neural tube defects (NTDs), oral clefts (OCs), heart defects (HDs), hypospadias, and other major birth defects, taking specific agent, timing, and indication into consideration. RESULTS: Drug-specific increased risks were observed for valproic acid in relation to NTDs [adjusted odds ratio (aOR), 9.7;, 95% confidence interval (CI), 3.4-27.5], OCs (aOR, 4.4; 95% CI, 1.6-12.2), HDs (aOR, 2.0; 95% CI, 0.78-5.3), and hypospadias (aOR. 2.4; 95% CI, 0.62-9.0), and for carbamazapine in relation to NTDs (aOR, 5.0; 95% CI, 1.9-12.7). Epilepsy history without AED use did not seem to increase risk. CONCLUSIONS: Valproic acid, which current guidelines suggest should be avoided in pregnancy, was most notable in terms of strength and breadth of its associations. Carbamazapine was associated with NTDs, even after controlling for folic acid use. Sample sizes were still too small to adequately assess risks of less commonly used AEDs, but our findings support further study to identify lower risk options for pregnant women. PMID- 21982489 TI - The Procedural Index for Mortality Risk (PIMR): an index calculated using administrative data to quantify the independent influence of procedures on risk of hospital death. AB - BACKGROUND: Surgeries and other procedures can influence the risk of death in hospital. All published scales that predict post-operative death risk require clinical data and cannot be measured using administrative data alone. This study derived and internally validated an index that can be calculated using administrative data to quantify the independent risk of hospital death after a procedure. METHODS: For all patients admitted to a single academic centre between 2004 and 2009, we estimated the risk of all-cause death using the Kaiser Permanente Inpatient Risk Adjustment Methodology (KP-IRAM). We determined whether each patient underwent one of 503 commonly performed therapeutic procedures using Canadian Classification of Interventions codes and whether each procedure was emergent or elective. Multivariate logistic regression modeling was used to measure the association of each procedure-urgency combination with death in hospital independent of the KP-IRAM risk of death. The final model was modified into a scoring system to quantify the independent influence each procedure had on the risk of death in hospital. RESULTS: 275 460 hospitalizations were included (137,730 derivation, 137,730 validation). In the derivation group, the median expected risk of death was 0.1% (IQR 0.01%-1.4%) with 4013 (2.9%) dying during the hospitalization. 56 distinct procedure-urgency combinations entered our final model resulting in a Procedural Index for Mortality Rating (PIMR) score values ranging from -7 to +11. In the validation group, the PIMR score significantly predicted the risk of death by itself (c-statistic 67.3%, 95% CI 66.6-68.0%) and when added to the KP-IRAM model (c-index improved significantly from 0.929 to 0.938). CONCLUSIONS: We derived and internally validated an index that uses administrative data to quantify the independent association of a broad range of therapeutic procedures with risk of death in hospital. This scale will improve risk adjustment when administrative data are used for analyses. PMID- 21982491 TI - Complications and survival after surgical treatment of 214 metastatic lesions of the humerus. AB - BACKGROUND: The humerus is the second most common long-bone site of metastatic bone disease. We report complications, risk factors for failure, and survival of a large series of patients operated on for skeletal metastases of the humerus. MATERIALS AND METHODS: This study was based on 208 patients treated surgically for 214 metastatic lesions of the humerus. Reconstructions were achieved by intramedullary nails in 148, endoprostheses in 35, plate fixation in 21, and by other methods in 10. RESULTS: The median age at surgery was 67 years (range, 29 87 years). Breast cancer was the primary tumor in 31%. The overall failure rate of the surgical reconstructions was 9%. The reoperation rate was 7% in the proximal humerus, 8% in the diaphysis, and 33% in the distal part of the bone. Among 36 operations involving an endoprosthesis, 2 were failures (6%) compared with 18 of 178 osteosynthetic devices (10%). In the osteosynthesis group, intramedullary nails failed in 7% and plate fixation failed in 22%. Multivariate Cox regression analysis showed that prostate cancer was associated with an increased risk of failure after surgery (hazard ratio, 7; P < 0.033). The cumulative survival after surgery was 40% (95% confidence interval [CI] 34-47) at 1 year, 21% (95% CI, 15-26) at 2 years, and 16% (95% CI, 12-19) at 3 years. CONCLUSIONS: Our method of choice is the cemented hemiprosthesis for pathologic proximal humeral fractures and interlocked intramedullary nail for lesions in the diaphysis. Pathologic fractures in the distal humerus are uncommon and associated with a very high reoperation rate. PMID- 21982492 TI - Extremely rare synovial chondrosarcoma arising from the elbow joint: case report and review of the literature. PMID- 21982493 TI - The design, synthesis and biological evaluation of novel URB602 analogues as potential monoacylglycerol lipase inhibitors. AB - We have synthesised an extensive series of URB602 analogues as inhibitors of monoacylglycerol lipase (MAGL), which is the major enzyme responsible for metabolising the endocannabinoid 2-arachidonylglycerol. The recently identified crystal structure of MAGL was used in the design strategy and revealed three possible binding sites for URB602 and the proposed analogues. A test series of carbamate analogues were docked into the identified sites to predict the most favourable binding location. The synthesised analogues of URB602 explored the biological effects of isosteric replacement, ring size and substitution, para substitution of the biphenyl moiety and the incorporation of a bicyclic element. The compounds were tested for their ability to inhibit human MAGL. The carbamate analogue 16 displayed the most significant inhibitory activity, reducing MAGL activity to 26% of controls at 100 MUM compared to 73% for the parent compound URB602. PMID- 21982494 TI - Continued exploration of biphenylsulfonamide scaffold as a platform for aggrecanase-1 inhibition. AB - Design, synthesis and structure-activity relationship of a series of biphenylsulfonamido-3-methylbutanoic acid based aggrecanase-1 inhibitors are described. In addition to robust aggrecanase-1 inhibition, these compounds also exhibit potent MMP-13 activity. In cell-based cartilage explants assay compound 48 produced 87% inhibition of proteoglycan degradation at 10 MUg/mL. Good pharmacokinetic properties were demonstrated by 46 with a half-life of 6h and bioavailability of 23%. PMID- 21982495 TI - Discovery, synthesis and SAR analysis of novel selective small molecule S1P4-R agonists based on a (2Z,5Z)-5-((pyrrol-3-yl)methylene)-3-alkyl-2 (alkylimino)thiazolidin-4-one chemotype. AB - High affinity and selective S1P(4) receptor (S1P(4)-R) small molecule agonists may be important proof-of-principle tools used to clarify the receptor biological function and effects to assess the therapeutic potential of the S1P(4)-R in diverse disease areas including treatment of viral infections and thrombocytopenia. A high-throughput screening campaign of the Molecular Libraries Small Molecule Repository was carried out by our laboratories and identified (2Z,5Z)-5-((1-(2-fluorophenyl)-2,5-dimethyl-1H-pyrrol-3-yl)methylene)-3-methyl-2 (methylimino) thiazolidin-4-one as a promising S1P(4)-R agonist hit distinct from literature S1P(4)-R modulators. Rational chemical modifications of the hit allowed the identification of a promising lead molecule with low nanomolar S1P(4) R agonist activity and exquisite selectivity over the other S1P(1-3,5)-Rs family members. The lead molecule herein disclosed constitutes a valuable pharmacological tool to explore the effects of the S1P(4)-R signaling cascade and elucidate the molecular basis of the receptor function. PMID- 21982496 TI - A novel potential therapeutic avenue for autism: design, synthesis and pharmacophore generation of SSRIs with dual action. AB - Autism symptoms are currently modulated by Selective Serotonin Reuptake Inhibitors (SSRIs). SSRIs slow onset of action limits their efficiency. The established synergistic activity of SSRIs and 5HT(1B/1D) autoreceptors antagonists motivated us to incorporate SSRIs and 5HT(1B/1D) antagonists in one 'hybrid' molecule. A library of virtual 'hybrid' molecules was designed using the tethering technique. A pharmacophore model was generated derived from 16 structurally diverse SSRIs (K(i)=0.013-5000 nM) and used as 3D query. Compounds with fit values (>=2) were chosen for synthesis and subsequent in vitro biological evaluation. Our pharmacophore model is a promising milestone to a class of SSRIs with dual action. PMID- 21982497 TI - Synthesis and in vitro antitubercular evaluation of novel sansanmycin derivatives. AB - Tuberculosis (TB) is a major health problem worldwide. A series of novel sansanmycin derivatives were designed, semi-synthesized and evaluated for their activity against drug-susceptible Mycobacterium tuberculosis strain H(37)Rv with sansanmycin A (SSA) as the lead. Among these analogs tested, compound 1d possessing an isopropyl group at the amino terminal afforded an increased antimycobacterial activity with a MIC value of 8 MUg/mL in comparison with SSA. Importantly, it was active for rifampicin- and isoniazid-resistant M. tuberculosis strain isolated from patients in China. These promising results offer an opportunity for further exploration of this novel class of analogs as antitubercular agents. PMID- 21982498 TI - Designing 2-aminoimidazole alkaloids analogs with anti-biofilm activities: structure-activities relationships of polysubstituted triazoles. AB - In order to discover novel probes that may help in the investigation and the control of bacterial biofilms, we have designed a library of triazole-based analogs of 2-aminoimidazole marine alkaloids: naamine A and isonaamine A. Twenty two compounds were screened for their biofilm inhibitory activity against two strains of Gram-negative bacteria. Four compounds were shown to act as non-toxic inhibitors of biofilm development without effect on bacterial growth even at high concentrations (100 MUM). PMID- 21982499 TI - 7-(4H-1,2,4-Triazol-3-yl)benzo[c][2,6]naphthyridines: a novel class of Pim kinase inhibitors with potent cell antiproliferative activity. AB - A novel class of pan-Pim kinase inhibitors was designed by modifying the CK2 inhibitor CX-4945. Introduction of a triazole or secondary amide functionality on the C-7 position and 2'-halogenoanilines on C-5 resulted in potent inhibitors of the Pim-1 and Pim-2 isoforms, with many analogs active at single digit nanomolar concentrations. The molecules inhibited the phosphorylation at Serine 112 of the apoptosis effector BAD, and had potent antiproliferative effects on the AML cell line MV-4-11 (IC(50) <30 nM). This work delivers an excellent lead-optimization platform for Pim targeting anticancer therapies. PMID- 21982500 TI - Identification of a novel RAMP-independent CGRP receptor antagonist. AB - Identification of an HIV integrase inhibitor with micromolar affinity for the CGRP receptor led to the discovery of a series of structurally novel CGRP receptor antagonists. Optimization of this series produced compound 16, a low molecular weight CGRP receptor antagonist with good pharmacokinetic properties in both rat and dog. In contrast to other nonpeptide antagonists, the activity of 16 was affected by the presence of divalent cations and showed evidence of an alternative, RAMP-independent CGRP receptor binding site. PMID- 21982501 TI - Is the Western diet adequate in copper? AB - Copper has been known to be essential for health for more than three quarters of a century. Myriad experiments with animals reveal that the cardiovascular, musculoskeletal and nervous systems are most sensitive to deficiency. Copper in the Western diet has been decreasing at least since the 1930s; half of the adult population consumes less than the amount recommended in the European Communities and the United Kingdom. At least one fourth of adults consume less than the estimated average requirement published for the United States and Canada. Hundreds of people have been reported in journals about medicine and neurology rather than nutrition to have impaired copper nutriture based on the criteria of low copper concentrations and low activities of enzymes dependent on copper in various fluids and tissues. In contrast, only 46 people have participated in depletion/repletion experiments needed to define requirements. Almost 1000 people have benefited from supplements containing copper in controlled trials. People deficient in copper are being identified increasingly; it is unknown if unusually high requirements or unusually low diets are causal. Alzheimer's disease, ischemic heart disease and osteoporosis are the most likely human illnesses from low copper intakes. PMID- 21982502 TI - A robust method for testing urinary iodine using a microtitre robotic system. AB - PROJECT: Iodine deficiency disorders are due to inadequate thyroid hormone production and 2 billion individuals worldwide are estimated to have insufficient iodine intake. Laboratory assessment methods include urinary iodine (UI) concentration, blood FT3, FT4, TSH and Thyroglobulin. The aim of this study was to set up a robust method for testing urinary iodine using a microtitre robotic system. PROCEDURE: The UI method described is based on the Sandell-Kolthoff reaction, which utilizes the catalytic role of iodine in the reduction of ceric ammonium sulphate in the presence of arsenious acid. This method was automated for use on microtitre robotic system. RESULTS: The method was compared with the currently employed manual Sandell-Kolthoff reaction method in our laboratory as reference. The two methods correlated well using weighted Deming regression analysis (slope=1.066, intercept=6.5, r=0.994; n=211). Interassay and intraassay variations were similar to the reference method, but cost analysis indicated a large reduction in costs related to increased throughput, and reduced consumables and labour. CONCLUSIONS: We have successfully adapted UI testing to an automated method, permitting cheaper, faster and robust screening of large numbers of patients and populations. The described protocol can be used on different microtitre robotic systems permitting up to 372 patient samples per run for 4 microtitre plate systems. PMID- 21982503 TI - Tuning surface charge property by floating gate field effect transistor. AB - Tuning surface charge property by a floating gate field effect transistor (FGFET) is proposed and analyzed for the first time. The FGFET has an additional floating gate electrode embedded inside the dielectric channel wall and is superior to the conventional FET to tune the surface charge property of a dielectric material in contact with an aqueous solution. PMID- 21982505 TI - Determination of volatile organic compounds as biomarkers of lung cancer by SPME GC-TOF/MS and chemometrics. AB - A method for qualitative and quantitative the determination of concentrations volatile organic compounds (VOCs) in human breath samples using solid phase microextraction (SPME) and gas chromatography-time of flight-mass spectrometry (GC-TOF/MS) has been carried out. They are employed for the preconcentration, separation and analysis of biological samples. The technique to rapid determination compounds present in human air, at the level of parts per billion (ppb) is applied. This method was optimized and evaluated. It showed linear correlations ranging from 0.83 to 234.05 ppb, limit of detection in the range of 0.31 to 0.75 ppb and precision, expressed as the RSD, was less then 10.00%. The unique combination of statistical methods allowed reduce the number of compounds to significant ones only and indicate the potential way to find the biomarkers of the lung cancer. Presented an analytical and statistical methods for detection composition of exhaled air could be applied as a potential non-intrusive tool for screening of lung cancer. PMID- 21982506 TI - Enhanced extraction of patchouli alcohol from Pogostemon cablin by microwave radiation-accelerated ionic liquid pretreatment. AB - A microwave radiation-accelerated ionic liquid pretreatment (MRAILP) was developed to enhance extraction of patchouli alcohol from Pogostemon cablin. 1-N butyl-3-methylimidazolium chloride ([C(4)mim]Cl) was selected as microwave absorbing and cellulose dissolution medium and microwave was applied to accelerate sample dissolution. The conditions of MRAILP including particle size, solvent, microwave pretreatment time and power and the ratio of ionic liquid (IL) to sample were optimized. Under the optimized conditions, the extraction yield of patchouli alcohol by the MRAILP was 1.94%, which has increased by 166% compared with microwave-assisted extraction. The recovery was in the range of 95.71-103.7% with relative standard deviation lower than 3.0%. It was a novel alternative extraction method for the fast extraction and determination of patchouli alcohol from Pogostemon cablin. PMID- 21982504 TI - Stressful life events and the serotonin transporter gene (5-HTT) in recurrent clinical depression. AB - BACKGROUND: An interaction between recent stressful life events (SLEs) and a serotonin transporter promoter polymorphism (5-HTTLPR) in depression has been inconsistently reported. Some of this variability may be due to a previous focus on sub-clinical depression, inclusion of individuals at the lower or upper ends of the age-span, or assumptions concerning the degree of dominance of the low expressing allele. Therefore, a large sample of patients with recurrent clinically diagnosed depression and controls screened for absence of depression was utilised to examine the moderating effect of each 5-HTTLPR genetic model on the association between SLEs and severe depressive episodes. METHOD: A sample of 1236 recurrent unipolar depression cases and 598 age-matched, never psychiatrically ill controls completed the List of Threatening Experiences Questionnaire to assess the number of SLEs experienced in the 6 months prior to the most severe depressive episode (cases) or interview (controls). DNA extracted from blood or cheek swabs was genotyped for the short (s) and long (l) alleles of 5-HTTLPR. RESULTS: A greater number of SLEs were reported by cases than controls and this held across all genotypic groups. There was no main effect of 5-HTTLPR on depression and no evidence of interaction between total SLEs and any of the 5 HTTLPR genetic models. The results were the same for men and women. LIMITATIONS: Utilisation of retrospective self-reported SLEs may have reduced the accuracy of the findings and the cross-sectional design prevents causal inference. CONCLUSIONS: This study failed to find evidence of gene-environment interplay in recurrent clinical depression. PMID- 21982507 TI - Identification of biomarkers for melamine-induced nephrolithiasis in young children based on ultra high performance liquid chromatography coupled to time-of flight mass spectrometry (U-HPLC-Q-TOF/MS). AB - Milk products contaminated with melamine caused renal disease in young children in mainland China in 2008. The present study was designed to identify potential markers and assess the underlying metabolomic mechanisms of melamine-induced nephrolithiasis in young children. Urine samples were collected from healthy children (n=74) and from children diagnosed with nephrolithiasis (n=73) with either a positive (n=40) or a negative (n=33) history of melamine exposure. Ultra high-performance liquid chromatography coupled to time of flight mass spectrometry (U-HPLC-MS/MS) was applied to profile the abundances of metabolites. Partial least squares-discriminant analysis (PLS-DA) was used to discriminate between the samples. Seven compounds were found to highly discriminate between healthy controls and nephrolithiasis patients with a history of melamine exposure. The critical markers such as proline and 5C-aglycone were the predominant markers in the control group and detected only rarely in nephrolithiasis patients with a history of melamine exposure. In contrast, hypoxanthine at was the most significant compound that distinguished nephrolithiasis patients with a history of melamine exposure. It was increased to 116.12+/-23.34 MUg/L (mean+/-S.D.) in the melamine-induced nephrolithiasis group, whereas the non-melamine group was at the level of 67.47+/-9.33 MUg/L (p<0.001). The biomarkers for melamine-induced nephrolithiasis identified by this study may have clinical application in determining the aetiology of renal disease in young children. PMID- 21982508 TI - The strengths and limitations of routine staging before treatment with abdominal CT in colorectal cancer. AB - BACKGROUND: Advanced colorectal cancer (CRC), either locally advanced, metastasized (mCRC) or both, is present in a relevant proportion of patients. The chances on curation of advanced CRC are continuously improving with modern multi modality treatment options. For incurable CRC the focus lies on palliation of symptoms, which is not necessarily a resection of the primary tumor. Both situations motivate adequate staging before treatment in CRC. This prospective observational study evaluates the outcomes after the introduction of routine staging with abdominal CT before treatment. METHODS: In a prospective observational study of 612 consecutive patients (2007-2009), the ability of abdominal CT to find liver metastases (LM), peritoneal carcinomatosis (PC) and T4 stage in colon cancer (CC) was analysed. RESULTS: Advanced CRC was present in 58% of patients, mCRC in 31%. The ability to find LM was excellent (99%), cT4 stage CC good (86%) and PC poor (33%). In the group of surgical patients with emergency presentations, the incidences of both mCRC (51%) and locally advanced colon cancer (LACC) (69%) were higher than in the elective group (20% and 26% respectively). Staging tended to be omitted more often in the emergency group (35% versus 12% in elective surgery). CONCLUSIONS: The strengths of staging with abdominal CT are to find LM and LACC, however it fails in diagnosing PC. On grounds of the incidence of advanced CRC, staging is warranted in patients with emergency presentations as well. PMID- 21982509 TI - Cytokines. PMID- 21982510 TI - Regulatory cells and cell signatures in clinical transplantation tolerance. AB - Experimental models of transplantation provide strong support for the role of regulatory cells in tolerance. However, limited studies of humans who display sustained tolerance following transplantation have not definitively demonstrated a role for regulatory cells in this process. Rather than excluding or minimizing the contribution of regulatory cells to the development of transplantation tolerance, we suggest the possibility that multiple lineages of cells exert regulatory effects that contribute to the development of tolerance, that these regulatory effects are not constant but vary over time, and that the role of regulatory cells varies based on the organ transplanted. More detailed studies will be necessary to elucidate the role of regulatory cells in clinical transplantation and tolerance. PMID- 21982511 TI - Essential role for B cells in transplantation tolerance. AB - T lymphocytes are the primary targets of immunotherapy in clinical transplantation. However, B lymphocytes are detrimental to graft survival by virtue of their capacity to present antigen to T cells via the indirect pathway of allorecognition and the generation of donor specific alloantibody. Furthermore, the long-term survival of organ allografts remains challenged by chronic rejection, a process in which activated B cells have been found to play a significant role. Therefore, the achievement of transplantation tolerance will likely require induction of both T and B cell tolerance to alloantigens. Moreover, human and animal investigations have shown that subsets of B cells, Transitional and Regulatory, are inherently tolerogenic. Developing therapeutic strategies that exploit these populations may be key to achieving transplantation tolerance. In this review we describe the current evidence for the essential role of B cells in transplant tolerance and discuss emerging B cell directed strategies to achieve allograft tolerance. PMID- 21982512 TI - The genomic impact of 100 million years of social evolution in seven ant species. AB - Ants (Hymenoptera, Formicidae) represent one of the most successful eusocial taxa in terms of both their geographic distribution and species number. The publication of seven ant genomes within the past year was a quantum leap for socio- and ant genomics. The diversity of social organization in ants makes them excellent model organisms to study the evolution of social systems. Comparing the ant genomes with those of the honeybee, a lineage that evolved eusociality independently from ants, and solitary insects suggests that there are significant differences in key aspects of genome organization between social and solitary insects, as well as among ant species. Altogether, these seven ant genomes open exciting new research avenues and opportunities for understanding the genetic basis and regulation of social species, and adaptive complex systems in general. PMID- 21982513 TI - Snat: a SNP annotation tool for bovine by integrating various sources of genomic information. AB - BACKGROUND: Most recently, with maturing of bovine genome sequencing and high throughput SNP genotyping technologies, a large number of significant SNPs associated with economic important traits can be identified by genome-wide association studies (GWAS). To further determine true association findings in GWAS, the common strategy is to sift out most promising SNPs for follow-up replication studies. Hence it is crucial to explore the functional significance of the candidate SNPs in order to screen and select the potential functional ones. To systematically prioritize these statistically significant SNPs and facilitate follow-up replication studies, we developed a bovine SNP annotation tool (Snat) based on a web interface. RESULTS: With Snat, various sources of genomic information are integrated and retrieved from several leading online databases, including SNP information from dbSNP, gene information from Entrez Gene, protein features from UniProt, linkage information from AnimalQTLdb, conserved elements from UCSC Genome Browser Database and gene functions from Gene Ontology (GO), KEGG PATHWAY and Online Mendelian Inheritance in Animals (OMIA). Snat provides two different applications, including a CGI-based web utility and a command-line version, to access the integrated database, target any single nucleotide loci of interest and perform multi-level functional annotations. For further validation of the practical significance of our study, SNPs involved in two commercial bovine SNP chips, i.e., the Affymetrix Bovine 10K chip array and the Illumina 50K chip array, have been annotated by Snat, and the corresponding outputs can be directly downloaded from Snat website. Furthermore, a real dataset involving 20 identified SNPs associated with milk yield in our recent GWAS was employed to demonstrate the practical significance of Snat. CONCLUSIONS: To our best knowledge, Snat is one of first tools focusing on SNP annotation for livestock. Snat confers researchers with a convenient and powerful platform to aid functional analyses and accurate evaluation on genes/variants related to SNPs, and facilitates follow-up replication studies in the post-GWAS era. PMID- 21982516 TI - Healthy by law: the missed opportunity to use laws for public health. AB - Health is the result of biological and social determinants; both are important. Nature dictates the laws for biological determinants; people create the laws for social determinants. Nature's laws are hard to discover and are eternal whether or not they suit humanity; people's laws are easily written and can be changed at anytime to suit humanity better. So why is it that the public health community, which expends much effort and expense probing natural laws, places negligible emphasis on collection, analysis, and making greater use of the world's public health laws? PMID- 21982515 TI - Comparing the immunosuppressive potency of naive marrow stromal cells and Notch transfected marrow stromal cells. AB - BACKGROUND: SB623 cells are expanded from marrow stromal cells (MSCs) transfected with a Notch intracellular domain (NICD)-expressing plasmid. In stroke-induced animals, these cells reduce infarct size and promote functional recovery. SB623 cells resemble the parental MSCs with respect to morphology and cell surface markers despite having been in extended culture. MSCs are known to have immunosuppressive properties; whether long-term culture of MSCs impact their immunomodulatory activity has not been addressed. METHODS: To assess the possible senescent properties of SB623 cells, we performed cell cycle related assays and beta-galactosidase staining. To assess the immunomodulatory activity of these expanded NICD-transfected MSCs, we performed co-cultures of SB623 cells or MSCs with either enriched human T cells or monocytes and assessed cytokine production by flow cytometry. In addition, we monitored the immunosuppressive activity of SB623 cells in both allogenic and xenogenic mixed lymphocyte reaction (MLR). RESULTS: Compared to MSCs, we showed that a small number of senescent-like cells appear in each lot of SB623 cells. Nevertheless, we demonstrated that these cells suppress human T cell proliferation in both the allogeneic and xenogeneic mixed lymphocyte reaction (MLR) in a manner comparable to MSCs. IL-10 producing T cells were generated and monocyte-dendritic cell differentiation was dampened by co culture with SB623 cells. Compared to the parental MSCs, SB623 cells appear to exert a greater inhibitory impact on the maturation of dendritic cells as demonstrated by a greater reduction in the surface expression of the co stimulatory molecule, CD86. CONCLUSION: The results demonstrated that the immunosuppressive activity of the expanded NICD-transfected MSCs is comparable to the parental MSCs, in spite of the appearance of a small number of senescent-like cells. PMID- 21982514 TI - Human epidermal growth factor receptor bispecific ligand trap RB200: abrogation of collagen-induced arthritis in combination with tumour necrosis factor blockade. AB - INTRODUCTION: Rheumatoid arthritis (RA) is a chronic disease associated with inflammation and destruction of bone and cartilage. Although inhibition of TNFalpha is widely used to treat RA, a significant number of patients do not respond to TNFalpha blockade, and therefore there is a compelling need to continue to identify alternative therapeutic strategies for treating chronic inflammatory diseases such as RA. The anti-epidermal growth factor (anti-EGF) receptor antibody trastuzumab has revolutionised the treatment of patients with EGF receptor-positive breast cancer. Expression of EGF ligands and receptors (known as HER) has also been documented in RA. The highly unique compound RB200 is a bispecific ligand trap that is composed of full-length extracellular domains of HER1 and HER3 EGF receptors. Because of its pan-HER specificity, RB200 inhibits responses mediated by HER1, HER2 and HER3 in vitro and in vivo. The objective of this study was to assess the effect of RB200 combined with TNF blockade in a murine collagen-induced arthritis (CIA) model of RA. METHODS: Arthritic mice were treated with RB200 alone or in combination with the TNF receptor fusion protein etanercept. We performed immunohistochemistry to assess CD31 and in vivo fluorescent imaging using anti-E-selectin antibody labelled with fluorescent dye to elucidate the effect of RB200 on the vasculature in CIA. RESULTS: RB200 significantly abrogated CIA by reducing paw swelling and clinical scores. Importantly, low-dose RB200 combined with a suboptimal dose of etanercept led to complete abrogation of arthritis. Moreover, the combination of RB200 with etanercept abrogated the intensity of the E-selectin-targeted signal to the level seen in control animals not immunised to CIA. CONCLUSIONS: The human pan-EGF receptor bispecific ligand trap RB200, when combined with low-dose etanercept, abrogates CIA, suggesting that inhibition of events downstream of EGF receptor activation, in combination with TNFalpha inhibitors, may hold promise as a future therapy for patients with RA. PMID- 21982517 TI - Towards risk reduction in non-cardiac surgery. PMID- 21982518 TI - Patient blood management is key before elective surgery. PMID- 21982519 TI - Treatment intensity at end of life--time to act on the evidence. PMID- 21982520 TI - The intensity and variation of surgical care at the end of life: a retrospective cohort study. AB - BACKGROUND: Although the extent of hospital and intensive-care use at the end of life is well known, patterns of surgical care during this period are poorly understood. We examined national patterns of surgical care in the USA among elderly fee-for-service Medicare beneficiaries in their last year of life. METHODS: We did a retrospective cohort study of elderly beneficiaries of fee-for service Medicare in the USA, aged 65 years or older, who died in 2008. We identified claims for inpatient surgical procedures in the year before death and examined the relation between receipt of an inpatient procedure and both age and geographical region. We calculated an end-of-life surgical intensity (EOLSI) score for each hospital referral region defined as proportion of decedents who underwent a surgical procedure during the year before their death, adjusted for age, sex, race, and income. We compared patient characteristics with Rao-Scott chi(2) tests, resource use with generalised estimating equations, regional differences with generalised estimating equations Wald tests, and end-of-life surgical intensity scores with Spearman's partial-rank-order correlation coefficients. FINDINGS: Of 1,802,029 elderly beneficiaries of fee-for-service Medicare who died in 2008, 31.9% (95% CI 31.9-32.0; 575,596 of 1,802,029) underwent an inpatient surgical procedure during the year before death, 18.3% (18.2-18.4; 329,771 of 1,802,029) underwent a procedure in their last month of life, and 8.0% (8.0-8.1; 144,162 of 1,802,029) underwent a procedure during their last week of life. Between the ages of 80 and 90 years, the percentage of decedents undergoing a surgical procedure in the last year of life decreased by 33% (35.3% [95% CI 34.7-35.9; 8858 of 25,094] to 23.6% [22.9-24.3; 3340 of 14,152]). EOLSI score in the highest intensity region (Munster, IN) was 34.4 (95% CI 33.7-35.1) and in the lowest intensity region (Honolulu, HI) was 11.5 (11.3 11.7). Regions with a high number of hospital beds per head had high end-of-life surgical intensity (r=0.37, 95% CI 0.27-0.46; p<0.0001), as did regions with high total Medicare spending (r=0.50, 0.41-0.58; p<0.0001). INTERPRETATION: Many elderly people in the USA undergo surgery in the year before their death. The rate at which they undergo surgery varies substantially with age and region and might suggest discretion in health-care providers' decisions to intervene surgically at the end of life. FUNDING: None. PMID- 21982521 TI - Preoperative anaemia and postoperative outcomes in non-cardiac surgery: a retrospective cohort study. AB - BACKGROUND: Preoperative anaemia is associated with adverse outcomes after cardiac surgery but outcomes after non-cardiac surgery are not well established. We aimed to assess the effect of preoperative anaemia on 30-day postoperative morbidity and mortality in patients undergoing major non-cardiac surgery. METHODS: We analysed data for patients undergoing major non-cardiac surgery in 2008 from The American College of Surgeons' National Surgical Quality Improvement Program database (a prospective validated outcomes registry from 211 hospitals worldwide in 2008). We obtained anonymised data for 30-day mortality and morbidity (cardiac, respiratory, CNS, urinary tract, wound, sepsis, and venous thromboembolism outcomes), demographics, and preoperative and perioperative risk factors. We used multivariate logistic regression to assess the adjusted and modified (nine predefined risk factor subgroups) effect of anaemia, which was defined as mild (haematocrit concentration >29-<39% in men and >29-<36% in women) or moderate-to-severe (<=29% in men and women) on postoperative outcomes. FINDINGS: We obtained data for 227,425 patients, of whom 69,229 (30.44%) had preoperative anaemia. After adjustment, postoperative mortality at 30 days was higher in patients with anaemia than in those without anaemia (odds ratio [OR] 1.42, 95% CI 1.31-1.54); this difference was consistent in mild anaemia (1.41, 1.30-1.53) and moderate-to-severe anaemia (1.44, 1.29-1.60). Composite postoperative morbidity at 30 days was also higher in patients with anaemia than in those without anaemia (adjusted OR 1.35, 1.30-1.40), again consistent in patients with mild anaemia (1.31, 1.26-1.36) and moderate-to-severe anaemia (1.56, 1.47-1.66). When compared with patients without anaemia or a defined risk factor, patients with anaemia and most risk factors had a higher adjusted OR for 30-day mortality and morbidity than did patients with either anaemia or the risk factor alone. INTERPRETATION: Preoperative anaemia, even to a mild degree, is independently associated with an increased risk of 30-day morbidity and mortality in patients undergoing major non-cardiac surgery. FUNDING: Vifor Pharma. PMID- 21982522 TI - Identification, preparation and UHPLC determination of process-related impurity in zolmitriptan. AB - A new impurity was detected and determined using gradient ion-pair UHPLC method with UV detection in zolmitriptan (ZOL). Using MS, NMR and IR study the impurity was identified as (4S,4'S)-4,4'-(2,2'-(4-(dimethylamino)butane-1,1-diyl)bis(3-(2 (dimethylamino) ethyl)-1H-indole-5,2-diyl))bis(methylene)di(oxazolidin-2-one) (ZOL-dimer). The standard of ZOL-dimer was consequently prepared via organic synthesis followed by semipreparative HPLC purification. The UHPLC method was optimized in order to selectively detect and quantify other known and unknown process-related impurities and degradation products of ZOL as well. The presented method which was validated with respect to linearity, accuracy, precision and selectivity has an advantage of a very quick UHPLC chromatographic separation (less than 7 min including re-equilibration time) and therefore is highly suitable for routine analysis of related substances and stability studies of ZOL. PMID- 21982523 TI - Conditional and specific inhibition of NF-kappaB in mouse pancreatic beta cells prevents cytokine-induced deleterious effects and improves islet survival posttransplant. AB - BACKGROUND: Islets are susceptible to damage by proinflammatory cytokines via activation of transcription factor NF-kappaB. We hypothesized that inhibition of NF-kappaB activity will decrease cytokine-mediated beta-cell injury and improve islet transplant functional outcome. METHODS: We created a transgenic mouse expressing a degradation resistant N-terminally deleted IkappaBalpha (DeltaNIkappaBalpha) under the control of a commercially available tetracycline controlled transcriptional activation system using a rat insulin promoter. Isolated islets from transgenic and control mouse strains were exposed to cytokines in vitro and assayed or transplanted. RESULTS: Western blot analysis showed that DeltaNIkappaBalpha was significantly increased with doxycycline treatment. Cytokine-induced NF-kappaB activation was significantly decreased in transgenic (0.065 +/- 0.013 absorbance value/MUg protein) vs control islets (0.128 +/- 0.006; P < .05). Suppression of cytokine-mediated NF-kappaB activity decreased expression of inducible nitric oxide synthase, monocyte chemoattractant protein-1, and interferon-gamma inducible protein-10 RNA transcripts, and significantly decreased nitric oxide production in transgenic islets (0.084 +/- 0.043 MUM/MUg protein) vs. controls (0.594 +/- 0.174; P < .01). The insulin stimulation index in islets exposed to cytokines was higher in transgenic vs controls (1.500 +/- 0.106 vs 0.800 +/- 0.098; P < .01). Syngeneic transplants of a marginal mass of intraportally infused transgenic islets resulted in a reversion to euglycemia in 69.2% of diabetic recipients at a mean of 7.8 +/- 1.1 days vs. 35.7% of control islet recipients reverting at a mean of 15.8 +/- 2.9 days (P < .05). CONCLUSION: Conditional and specific suppression of NF-kappaB activity in beta cells protected islets from cytokine-induced dysfunction in vitro and in vivo. These results provide a proof of principle that inhibition of NF-kappaB activity in donor islets enhances function and improves the outcome of islet transplantation. PMID- 21982524 TI - Alveolar macrophage activation in obese patients with obstructive sleep apnea. AB - BACKGROUND: Classically, activated macrophages in adipose tissue, liver, and muscle have been implicated in many conditions associated with obesity, including insulin resistance and the metabolic syndrome. Despite numerous pulmonary comorbidities and the sentinel role alveolar macrophages play in innate immunity and lung homeostasis, their activation status has not been examined in these patients. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has been shown to be a negative regulator of inflammation in addition to regulating lipid and glucose metabolism. PPAR-gamma is expressed constitutively in healthy alveolar macrophages and decreased on activation. We hypothesized that PPAR-gamma would be downregulated in alveolar macrophages from obese patients with obstructive sleep apnea (OSA) in the absence of overt lung disease. METHODS: Alveolar macrophages were obtained by bronchoalveolar lavage from obese individuals with and without OSA and healthy controls. RESULTS: Data indicated that PPAR-gamma functional activity was decreased by 48% in obese with OSA and 26% without OSA (P < .05). In obese patients with OSA, PPAR-gamma mRNA was decreased 2-fold compared with controls (P < .05), whereas obese patients without OSA, it was not different. Regardless of OSA, alveolar macrophages of obese patients demonstrated increased interleukin-6 mRNA. CONCLUSION: These findings are consistent with the presence of classic macrophage activation and an inflammatory lung environment. Data from this study suggest that alveolar macrophage dysfunction becomes aggravated in OSA and may increase pulmonary disease susceptibility. PMID- 21982525 TI - Contrast-enhanced ultrasonography for localization of pathologic glands in patients with primary hyperparathyroidism. AB - BACKGROUND: The localization of enlarged parathyroid glands might, depending on size, histology, and concomitant goiter, be difficult in some patients. In the presented study, contrast-enhanced ultrasonography (CEUS) was applied as a new diagnostic tool to detect the site of parathyroid lesions. METHODS: Thirty patients underwent operation for primary hyperparathyroidism (pHPT) between 8/2009 and 6/2010. Contrast-enhanced ultrasonography (CEUS) using a linear probe (6-9 MHz, LOGIQE9/GE), fundamental B scan, and Doppler ultrasonography, (99m)Technetium-sestamibi scintigraphy and magnetic resonance imaging (MRI) were performed in all patients preoperatively. The diagnostic sensitivity of the procedures, time requirements, and overall costs were analyzed. RESULTS: Using CEUS, all 31 pathologic glands could be detected, compared with 23 using conventional ultrasonography, 25 using (99m)Technetium-sestamibi scintigraphy and 22 using MRI (P = .015). Costs and time requirement were less using CEUS as compared with (99m)Technetium-scintigraphy and MRI examinations (P = .002). Minimally invasive, video-assisted parathyroidectomy could be performed successfully based on CEUS findings in all but 7 patients who required concomitant thyroid surgery or had underwent previous thyroid operations. All patients showed normal serum levels of calcium and parathyroid hormone serum levels 3 months after parathyroidectomy. CONCLUSION: CEUS represents a highly sensitive and cost-efficient method for localization of pathologic parathyroid glands in patients with pHPT. Future studies should confirm these findings in order to establish CEUS as a standard diagnostic procedure. PMID- 21982527 TI - An osseous lesion in a 10-year-old boy with Hodgkin's lymphoma: a case report. AB - INTRODUCTION: Osseous involvement of Hodgkin's lymphoma is uncommon. When osteolytic lesions are seen on imaging it is important to evaluate potential other causes. CASE PRESENTATION: We report the case of a 10-year-old Caucasian boy who presented to our facility with a bony lesion of the right clavicle and enlarged cervical lymph nodes. A simultaneous biopsy of the lymph node and of the osteolytic process of his right proximal clavicle was performed and revealed two different kinds of lesions: a mixed cellularity Hodgkin's lymphoma and an osteochondroma. CONCLUSIONS: Since the latter is a common benign bone tumor, which should not interfere with the staging of the lymphoma, we emphasize the importance of ensuring that all efforts are made to acquire a diagnostic biopsy of all atypical lesions. PMID- 21982526 TI - Roles of thymidylate synthase and dihydropyrimidine dehydrogenase expression in blood as predictors of response to multimodal therapy in esophageal cancer. AB - BACKGROUND: Thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD) RNA expression in peripheral blood was examined as a noninvasive molecular predictor of response to neoadjuvant radiochemotherapy in patients with locally advanced cancer of the esophagus. METHODS: Blood samples were drawn from 29 patients with esophageal cancer (10 squamous cell carcinomas and 19 adenocarciomas) before neoadjuvant radiochemotherapy. After extraction of cellular tumor RNA from blood samples, quantitative expression analysis of TS and DPD was performed with quantitative real-time reverse-transcription polymerase chain reaction. RESULTS: Twenty of 29 (68%) of patients had a minor histopathologic response, and 9 of 29 (32%) had a major response to neadjuvant radiochemotherapy. RNA expression in the blood of patients was detectable for TS in 86%, for DPD in 97%, and in 100% for beta-actin. No significant associations were detected between TS and DPD expression levels and clinical variables of the patients. A high expression level for TS was associated with a minor response to neoadjuvant treatment (P = .046), while there was no significant association between DPD and response to therapy. Combined analysis of TS and DPD expression increased the specificity for the prediction of response to 100%. No major responder to therapy had high expression levels for both genes in their peripheral blood. CONCLUSION: Quantitation of TS and DPD in peripheral blood may be a highly specific analysis to identify a subset of patients who do not respond to neoadjuvant radiochemotherapy and may therefore prevent expensive, noneffective, and potentially harmful therapies in a substantial number of patients with esophageal cancer. PMID- 21982528 TI - Prevention of AIDS-associated cryptococcosis in resource-poor areas. PMID- 21982529 TI - Primary prophylaxis of cryptococcal disease with fluconazole in HIV-positive Ugandan adults: a double-blind, randomised, placebo-controlled trial. AB - BACKGROUND: Cryptococcal disease remains an important cause of morbidity and mortality in HIV-infected individuals in sub-Saharan Africa, despite the introduction of antiretroviral therapy. We studied fluconazole as primary prophylaxis against cryptococcal disease in patients awaiting or starting antiretroviral therapy in Uganda. METHODS: In this prospective, double-blind randomised controlled trial, we enrolled HIV-positive adults with CD4 counts less than 200 cells per MUL, cryptococcal antigen (CrAg)-negative, naive for antiretroviral therapy, and coming from five local AIDS organisations in Masaka district, Uganda. Enrolment took place between Sept 14, 2004, and Feb 1, 2008. Participants were randomly allocated to placebo or 200 mg fluconazole three times per week (1:1) in blocks of 40. Randomisation was done with ralloc procedure in Stata. Participants were reviewed after 4 weeks and referred for antiretroviral therapy, then seen every 8 weeks. Participants discontinued trial treatment when CD4 counts reached 200 cells per MUL (median 197 days). Primary endpoints were invasive cryptococcal disease and all-cause mortality. Secondary endpoints were time to first episode and incidence of oesophageal candidosis, time to first episode and incidence of oropharyngeal or vaginal candidosis, and time to first hospital admission or death. The primary safety endpoint was cessation of trial drug because of transaminase concentrations higher than five times the upper limit of normal (ULN), or other major adverse events. Analyses were done by intention to treat and included all participants enrolled in the trial. Participants and researchers were masked to group assignment. This trial is registered with controlled-trials.com, number ISRCTN 76481529. RESULTS: Of 1519 individuals enrolled, 760 participants received fluconazole and 759 received placebo. 19 developed cryptococcal disease, one in the fluconazole group and 18 in the placebo group (p=0.0001); adjusted HR (aHR) 18.7 (95% CI 2.5-140.7). One case of cryptococcal disease could be prevented by treating 44.6 patients with baseline CD4 counts lower than 200 cells per MUL. Fluconazole was effective against cryptococcal disease both before (aHR=11.0 [1.4-85.3]) and after start of antiretroviral therapy (no cases in fluconazole vs seven cases on placebo). Seven participants died from cryptococcal disease, none in the fluconazole group. All cause mortality (n=189) did not differ between the two groups (p=0.46). Fluconazole reduced the time to first episode of oesophageal, and oropharyngeal and vaginal candidosis, as well as the incidence of all candidosis (p<0.0001), but had no effect on hospital admission or death. The frequency of elevated transaminases (>5*ULN) was similar between groups (aHR=0.94 [0.65-1.35]). CONCLUSIONS: Fluconazole was safe and effective as primary prophylaxis against cryptococcal disease, both before and during early antiretroviral treatment. Cryptococcal infection was less common than anticipated because of the rapid commencement of antiretroviral therapy and exclusion of those with positive CrAg. In patients with negative CrAg on screening, fluconazole prophylaxis can prevent cryptococcal disease while waiting for and in the early weeks of antiretroviral therapy, particularly in those with CD4 counts of less than 100 cells per MUL. FUNDING: Medical Research Council, UK, and Rockefeller Foundation. PMID- 21982530 TI - I see into your mind too well: working memory adjusts the probability judgment of others' mental states. AB - Although an increasing number of studies on adults have indicated that working memory (WM) contributes to the ability to understand the mental states of others (i.e., theory of mind), the detailed mechanism by which WM contributes to successful reasoning has not previously been revealed. This study shows that WM modulates the degree of attribution of one's own knowledge to others' mental states. Participants were asked to read a story twice (Experiment 2) or as carefully as possible (Experiment 3) and to estimate the probability percentages of possible choices for a naive protagonist's behavior. The participants were then asked to maintain either a two- or seven-letter alphabet string (i.e., a light or heavy WM load, respectively) during the probability estimation but not during the story comprehension. The results showed that compared to the participants with a light WM load, those with a heavy WM load estimated a significantly higher probability of the choice indicating that the protagonist would behave on the basis of a fact that the participants knew but the protagonist did not. This result indicates that WM moderates the extent to which adults attribute their own knowledge to others' mental states. The role of WM in theory of mind and in heuristic strategy for making probability judgments was then discussed. PMID- 21982531 TI - Bayesian confusions surrounding simplicity and likelihood in perceptual organization. AB - In the study of perceptual organization, the Occamian simplicity principle (which promotes efficiency) and the Helmholtzian likelihood principle (which promotes veridicality) have been claimed to be equivalent. Proposed models of these principles may well yield similar outcomes (especially in everyday situations), but as argued here, claims that the principles are equivalent confused subjective probabilities (which are used in Bayesian models of the Occamian simplicity principle) and objective probabilities (which are needed in Bayesian models of the Helmholtzian likelihood principle). Furthermore, Occamian counterparts of Bayesian priors and conditionals have led to another confusion, which seems to have been triggered by a dual role of regularity in perception. This confusion is discussed by contrasting complete and incomplete Occamian approaches to perceptual organization. PMID- 21982532 TI - Blood parameters in Swedish dairy herds with high or low incidence of displaced abomasum or ketosis. AB - Sixty dairy herds were studied to investigate the association between long-term incidence of displaced abomasum and clinical ketosis and body condition score and blood profiles, including parameters estimating energy metabolism and hepatic lipidosis in the periparturient period and early lactation. Blood samples were taken around parturition and in early lactation from cows without apparent clinical symptoms of metabolic disorders. A difference in metabolism between high and low incidence herds was shown post-partum by a lower metabolic index (the revised Quantitative Insulin Sensitivity Check Index, RQUICKI), and tendencies for higher concentrations of glucose, insulin and non-esterified fatty acids in the high incidence herds. High incidence herds had more cows and produced on average 1400kg energy-corrected milk per cow per year more than the low incidence herds. No differences were found in parameters reflecting liver cell damage. In the first 3weeks post-partum the RQUICKI was a more sensitive marker of herds with a high incidence of displaced abomasum and clinical ketosis than any of the individual parameters, but further research is needed before practical applications of the RQUICKI can be foreseen. PMID- 21982533 TI - Electrochemical study of nitrobenzene reduction on galvanically replaced nanoscale Fe/Au particles. AB - Nanoscale Fe/Au particles were fabricated on glassy carbon substrates by electrodeposition of Fe and the subsequent galvanic replacement with Au. The particles were characterized by scanning electron microscopy and transmission electron microscopy, and a hollow structure was found. The process and mechanism of electrochemical reduction of nitrobenzene on Fe/Au particles were studied by cyclic voltammetry and constant-potential electrolysis. The results showed that nanoscale Fe/Au particles exhibited higher catalytic activity than bulk gold for nitrobenzene reduction. Nitrobenzene reduction proceeded following different pathways with different electrolyte compositions. The removal rate of nitrobenzene on nanoscale Fe/Au particles was up to 97% with electrolysis within 120 min at -0.35 V in 0.1 M H(2)SO(4) and aniline was found to be the electrolysis product. PMID- 21982534 TI - Influence of saliva, gastric and intestinal phases on the prediction of As relative bioavailability using the Unified Bioaccessibility Research Group of Europe Method (UBM). AB - In this study, As-contaminated soils (n=12) were assessed for As bioaccessibility using the Unified Bioaccessibility Research Group of Europe in vitro method (UBM) incorporating gastric, saliva-gastric or saliva-gastric-intestinal phases. Arsenic bioaccessibility was compared to previous published As relative bioavailability data for these soils to determine the correlation between in vitro and in vivo data. Comparison of in vitro and in vivo data indicated that the correlation between As bioaccessibility (UBM) and As relative bioavailability (swine assay) was similar irrespective of the in vitro phase used for its determination. The UBM incorporating all phases (saliva-gastric-intestinal) provided the best in vivo-in vitro correlation (slope=1.08; R(2)=0.59), however there was no significant difference in the goodness of fit (R(2) ranged from 0.48 to 0.59) or the slope of the lines (0.93-1.08) for either variation of the UBM (P=0.9946). This indicates that there was no improvement in the As relative bioavailability predictive capabilities when the UBM was extended from a single gastric phase to saliva-gastric or saliva-gastric-intestinal phases. PMID- 21982535 TI - Procedure to use phosphogypsum industrial waste for mineral CO2 sequestration. AB - Industrial wet phosphoric acid production in Huelva (SW Spain) has led to the controversial stockpiling of waste phosphogypsum by-products, resulting in the release of significant quantities of toxic impurities in salt marshes in the Tinto river estuary. In the framework of the fight against global climate change and the effort to reduce carbon dioxide emissions, a simple and efficient procedure for CO(2) mineral sequestration is presented in this work, using phosphogypsum waste as a calcium source. Our results demonstrate the high efficiency of portlandite precipitation by phosphogypsum dissolution using an alkaline soda solution. Carbonation experiments performed at ambient pressure and temperature resulted in total conversion of the portlandite into carbonate. The fate of trace elements present in the phosphogypsum waste was also investigated, and trace impurities were found to be completely transferred to the final calcite. We believe that the procedure proposed here should be considered not only as a solution for reducing old stockpiles of phosphogypsum wastes, but also for future phosphoric acid and other gypsum-producing industrial processes, resulting in more sustainable production. PMID- 21982536 TI - Decontamination of waters polluted with simazine by sorption on mesoporous metal oxides. AB - Two mesoporous metal oxides, Al(2)O(3) and Fe(2)O(3), were evaluated as regards their ability to remove simazine, a highly persistent herbicide of s-triazines, using a batch equilibrium method. The effect of several experimental parameters such as pH, contact time, initial concentration and sorbent dosage on the sorption of the herbicide was investigated. The maximum sorption of simazine on Al(2)O(3) and Fe(2)O(3) was observed at pH 6.5 and 3.5, respectively. The different sorption capacities of the two oxides were explained considering a set of factors affecting the sorption process such as the surface area and the porosity. The kinetics of sorption on both oxides was described using a pseudo second-order model. The sorption of simazine on Fe(2)O(3) was faster in comparison to that observed on Al(2)O(3). It was shown that aluminum oxide can be regenerated by incineration, and consequently can be considered for industrial treatment systems designed to mitigate the pesticide pollution in the aquatic environments. PMID- 21982537 TI - Polybrominated diphenyl ethers in water, sediment, soil, and biological samples from different industrial areas in Zhejiang, China. AB - Polybrominated diphenyl ethers (PBDEs) have been used extensively in electrical and electronic products, but little is known about their distribution in the environment surrounding the manufacturing factories. This study reports PBDE contamination in various matrices from the location (Liushi, Zhejiang province) that produces more than 70% of the low-voltage electrical appliances in China. Additionally, PBDE contamination was compared with other industries such as the e waste recycling business (Fengjiang) in the same region. Specifically, we measured seven PBDE congeners (BDEs - 47, 99, 100, 153, 154, 183, and 209) in water, sediment, soil, plant, and animal tissues from four different areas in this region. The present study revealed elevated PBDE concentrations in all matrices collected from Liushi and Fengjiang in comparison with highly industrialized areas without significant PBDE contamination sources. In water samples, there were large variations of PBDE content and composition across different areas. In sediment/soil and biological samples, BDE-209 was the predominant congener and this could be due to the abundant usage of deca-BDE mixtures in China. Our findings provide the very first data on PBDE contamination in the local environments surrounding the electronics industry, and also reveal widespread PBDE contamination in highly industrialized coastal regions of China. PMID- 21982538 TI - Electrocoagulation treatment of simulated floor-wash containing Reactive Black 5 using iron sacrificial anode. AB - Floor-wash from dye finishing plant is a major source of color and wastewater volume for dyes industries. Batch electrocoagulation (EC) of simulated floor-wash containing Reactive Black 5 (RB5) was studied as a possible pretreatment option. More than 90% of initial 25mg/L of RB5 was removed at current densities of 4.5, 6, and 7.5 mA/cm(2) in the presence of Na(2)SO(4) and NaCl as supporting electrolytes; in less than one hour. Identical k(obs) (pseudo first-order reaction rate constant) values were obtained at initial pH of 3.74 for both electrolytes. However, at initial pH of 6.6, k(obs) values decreased in the presence of Na(2)SO(4) and remained same for NaCl as compared to that at pH 3.74. Highest extent of decolorization and k(obs) values were obtained at initial pH 9.0 for both electrolytes. Under identical conditions, specific energy consumption (SEC) was almost half in the presence of NaCl (~29 kWh/kg RB5) than that of Na(2)SO(4). Vinyl sulfone (VS) was detected as one of the products of EC indicating reduction of azo bonds as a preliminary step of decolorization. Mechanism of decolorization with respect to various experimental conditions was delineated. Generation and accumulation of VS was dependent on initial pH and type of electrolyte. Results of this study revealed that EC in the presence of sodium chloride can be efficiently used as a primary treatment for decolorization of floor-wash containing RB5. PMID- 21982539 TI - Comparative study of NO removal in surface-plasma and volume-plasma reactors based on pulsed corona discharges. AB - Nitric oxide (NO) conversion has been studied for two different types of atmospheric-pressure pulsed-corona discharges, one generates a surface-plasma and the other provides a volume-plasma. For both types of discharges the energy cost for NO removal increases with decreasing oxygen concentration and initial concentration of NO. However, the energy cost for volume plasmas for 50% NO removal, EC(50), from air was found to be 120 eV/molecule, whereas for the surface plasma, it was only 70 eV/molecule. A smaller difference in energy cost, but a higher efficiency for removal of NO was obtained in a pure nitrogen atmosphere, where NO formation is restricted due to the lack of oxygen. For the volume plasma, EC(50) in this case was measured at 50 eV/molecule, and for the surface plasma it was 40 eV/molecule. Besides the higher NO removal efficiency of surface plasmas compared to volume plasmas, the energy efficiency of surface plasmas was found to be almost independent of the amount of electrical energy deposited in the discharge, whereas the efficiency for volume plasmas decreases considerably with increasing energy. This indicates the possibility of operating surface plasma discharges at high energy densities and in more compact reactors than conventional volume discharges. PMID- 21982540 TI - Bromate removal by anaerobic bacterial community: mechanism and phylogenetic characterization. AB - A highly bromate resistant bacterial community and with ability for bromate removal was obtained from a sulphate-reducing bacteria enrichment consortium. This community was able to remove 96% of bromate and 99% of sulphate from an aqueous solution containing 40 MUM bromate and 10 mM sulphate. Moreover, 93% of bromate was removed in the absence of sulphate. Under this condition bromate was reduced stoichiometrically to bromide. However, in the presence of sulphate only 88% of bromate was reduced to bromide. Although, bromate removal was not affected by the absence of sulphate, this anion promoted a modification on the structure of the bacterial community. Phylogenetic analysis of 16S rRNA gene showed that the community grown in the presence of bromate and sulphate was mainly composed by bacteria closely to Clostridium and Citrobacter genera, while the community grown in the absence of sulphate was predominantly composed by Clostridium genus. It is the first time that Clostridium and Citrobacter genera are reported as having bromate removal ability. Furthermore, bromate removal by the consortium predominantly composed by Clostridium and Citrobacter genera occurred by enzymatic reduction and by extracellular metabolic products, while the enzymatic process was the only mechanism involved in bromate removal by the consortium mainly composed by Clostridium genus. PMID- 21982541 TI - Crystallization evolution, microstructure and properties of sewage sludge-based glass-ceramics prepared by microwave heating. AB - A Microwave Melting Reactor (MMR) was designed in this study which improved the microwave adsorption of sewage sludge to prepare glass-ceramics. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM) were used for the study of crystallization behavior and microstructure of the developed glass-ceramics. DSC and XRD analysis revealed that crystallization of the nucleated specimen in the region of 900-1000 degrees C resulted in the formation of two crystalline phases: anorthite and wollastonite. When the crystallization temperature increased from 900 to 1000 degrees C, the tetragonal wollastonite grains were subjected to tensile microstresses, causing the cracking of crystal. Al ions substituted partially Si ions and occupied tetrahedral sites, giving rise to the formation of anorthite. The relationship between microwave irradiation and crystal growth was studied and the result indicated that the microwave selective heating suppressed the crystal growth, giving apparent improvements in the properties of the glass-ceramics. The glass-ceramics products exhibited bending strength of 86.5-93.4 MPa, Vickers microhardness of 6.12-6.54 GPa and thermal expansion coefficient of 5.29-5.75 * 10(-6)/ degrees C. The best chemical durability in acid and alkali solutions was 1.32-1.61 and 0.41-0.58 mg/cm(2), respectively, showing excellent durability in alkali solution. PMID- 21982542 TI - The use of 3D laser imaging and a new breast replica cast as a method to optimize autologous breast reconstruction after mastectomy. AB - Aesthetically pleasing and symmetrical breasts are the goal of reconstructive breast surgery. Sometimes, however, multiple procedures are needed to improve a reconstructed breast's symmetry and appearance. In order to avoid additional corrective procedures, we have developed a new method that uses a reverse engineering technique to produce what we call a new breast replica cast (NBRC). The NBRC is a mould of the contralateral healthy breast, designed according to preoperative laser 3D images. During surgery, the mould is used to help shape the new breast. With this method, we are able to achieve breast symmetry in terms of volume, projection, contour, and position on the chest wall more accurately, more quickly, and more safely than before. PMID- 21982543 TI - Anti-N-methyl-D-aspartate-receptor encephalitis: cognitive profile in two children. AB - BACKGROUND: Anti-N-Methyl D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder associated with antibodies against NMDAR resulting in a characteristic neuropsychiatric syndrome characterized by seizures, dyskinesias, and cognitive impairment. The extent and specific tasks associated with cognitive dysfunction in anti-NMDAR encephalitis have not been fully investigated. AIMS: To describe cognitive and neuropsychological profile in two children with anti-NMDAR encephalitis. METHODS: Clinical, laboratory, cognitive and neuropsychological assessments have been performed. Cognitive functions have been evaluated one year after the disease onset, at age 4 years and 10 months in one patient and at age 5 years and 5 months in the other subject. The first patient has been re-assessed one year after the first evaluation. RESULTS: Both children, who were reported to be normal before disease onset, showed a severe neurological impairment during the acute phase of disease with progressive substantial recovery following treatment. Selective and prolonged attention, activation and integration of semantic information and verbal fluency were particularly impaired. Significant improvements were observed at neuropsychological re-assessment. CONCLUSIONS: Executive dysfunction seems to be the "core" of the neuropsychological profile of children with anti-NMDAR encephalitis. Cognitive abilities may be, at least to some extent, recovered providing that immunomodulatory treatment and specific psychomotor and pedagogical therapy are started soon after disease onset. PMID- 21982544 TI - Gene expression heterogeneities in embryonic stem cell populations: origin and function. AB - Stem and progenitor cells are populations of cells that retain the capacity to populate specific lineages and to transit this capacity through cell division. However, attempts to define markers for stem cells have met with limited success. Here we consider whether this limited success reflects an intrinsic requirement for heterogeneity with stem cell populations. We focus on Embryonic Stem (ES) cells, in vitro derived cell lines from the early embryo that are considered both pluripotent (able to generate all the lineages of the future embryo) and indefinitely self renewing. We examine the relevance of recently reported heterogeneities in ES cells and whether these heterogeneities themselves are inherent requirements of functional potency and self renewal. PMID- 21982545 TI - Market Access Agreements for pharmaceuticals in Europe: diversity of approaches and underlying concepts. AB - BACKGROUND: Market Access Agreements (MAA) between pharmaceutical industry and health care payers have been proliferating in Europe in the last years. MAA can be simple discounts from the list price or very sophisticated schemes with inarguably high administrative burden. DISCUSSION: We distinguished and defined from the health care payer perspective three kinds of MAA: Commercial Agreements (CA), Payment for Performance Agreements (P4P) and Coverage with Evidence Development (CED). Apart from CA, the agreements assumed collection and analysis of real-life health outcomes data, either from a cohort of patients (CED) or on per patient basis (P4P). We argue that while P4P aim at reducing drug cost to payers without a systematic approach to addressing uncertainty about drugs' value, CED were implemented provisionally to reduce payer's uncertainty about value of a medicine within a defined time period. SUMMARY: We are of opinion that while CA and P4P have a potential to reduce payers' expenditure on costly drugs while maintaining a high list price, CED address initial uncertainty related to assessing the real-life value of new drugs and enable a final HTA recommendation or reimbursement and pricing decisions. Further, we suggest that real cost to health care payers of drugs in CA and P4P should be made publicly available in a systematic manner, to avoid a perverse impact of these MAA types on the international reference pricing system. PMID- 21982547 TI - [Congenital oral mucoceles: presentation of four new clinical cases]. PMID- 21982548 TI - [Thrombolytic therapy using a low dose of tissue plasminogen activator in children]. AB - OBJECTIVE: To analyse the efficacy and side effects of low doses of tissue plasminogen activator for the treatment of acute arterial and/or venous thrombosis in children. PATIENTS AND METHODS: Prospective observational clinical study. 18 children between 1 months and 11 years treated with low doses (0.01 0.06 mg/kg/h) of continuous intravenous thrombolytic therapy with t-PA were studied. RESULTS: A total of 94% of patients improved with low doses t-PA (72% complete resolution of the thrombosis and 22% partial resolution). One patient suffered a severe haemorrhage secondary to t-Pa and had to stop the treatment. The incidence of severe side effects was low (5%) CONCLUSIONS: Thrombolytic therapy with low doses of t-PA (0.01-0.05 mg/kg/h) is effective in a high percentage of children with acute arterial and/or venous thrombosis and produces a relatively low frequency of side effects. PMID- 21982546 TI - RNA-binding proteins and gene regulation in myogenesis. AB - Skeletal muscle development, repair and function are dependent on highly coordinated expression of many genes. RNA-binding proteins are crucial determinants of gene expression in the health and disease of various tissues, including skeletal muscle. A variety of RNA-binding proteins are associated with a transcript during its life cycle and define the lifetime, cellular localization, processing and rate at which that transcript is translated and ultimately degraded. The focus of this review is to highlight the roles of the best-characterized RNA-binding proteins in muscle, including HuR, KSRP, CUGBP1, PABPN1, Lin-28 and TTP. Recent studies indicate key functions for these RNA binding proteins in different aspects of muscle physiology. Understanding the role of specific RNA-binding proteins in skeletal muscle will provide insights not only into basic mechanisms regulating gene expression in muscle, but also into the etiology and pathology of muscle disease. PMID- 21982549 TI - [Conservative treatment of brain abcesses secondary to staphylococcal endocarditis]. PMID- 21982550 TI - [Congenital para-esophageal hiatus hernia as a cause of severe hyporegenerative anemia]. PMID- 21982551 TI - [Clostridium difficile infection in child with no previous risk]. PMID- 21982552 TI - [Symptomatic hypocalcaemia as a first sign of coeliac disease]. PMID- 21982553 TI - [3q29 microduplication syndrome]. AB - 3q29 microduplication (MIM 611936) is rare syndrome characterized by moderate mental retardation, craniofacial dysmorphic features and musculoskeletal anomalies. The size of the minimal critical region is about 1.73 Mb. It is flanked by repetitive sequences and it is similar in size to the reciprocal 3q29 microdeletion, suggesting a non-allelic homologous recombination event (NAHR) at flanking LCR sequences as its aetiological mechanism. We describe a new familial case with variable expressivity. PMID- 21982554 TI - [HTLV-1 infection. An underdiagnosed entity in paediatrics?]. PMID- 21982555 TI - Cognitive flexibility in verbal and nonverbal domains and decision making in anorexia nervosa patients: a pilot study. AB - BACKGROUND: This paper aimed to investigate cognitive rigidity and decision making impairments in patients diagnosed with Anorexia Nervosa Restrictive type (AN-R), assessing also verbal components. METHODS: Thirty patients with AN-R were compared with thirty age-matched healthy controls (HC). All participants completed a comprehensive neuropsychological battery comprised of the Trail Making Test, Wisconsin Card Sorting Test, Hayling Sentence Completion Task, and the Iowa Gambling Task. The Beck Depression Inventory was administered to evaluate depressive symptomatology. The influence of both illness duration and neuropsychological variables was considered. Body Mass Index (BMI), years of education, and depression severity were considered as covariates in statistical analyses. RESULTS: The AN-R group showed poorer performance on all neuropsychological tests. There was a positive correlation between illness duration and the Hayling Sentence Completion Task Net score, and number of completion answers in part B. There was a partial effect of years of education and BMI on neuropsychological test performance. Response inhibition processes and verbal fluency impairment were not associated with BMI and years of education, but were associated with depression severity. CONCLUSIONS: These data provide evidence that patients with AN-R have cognitive rigidity in both verbal and non verbal domains. The role of the impairment on verbal domains should be considered in treatment. Further research is warranted to better understand the relationship between illness state and cognitive rigidity and impaired decision-making. PMID- 21982556 TI - The association of maternal and fetal glucose homeostasis with fetal adiposity and birthweight. AB - OBJECTIVE: To examine the association between maternal and fetal glucose levels and fetal adiposity and infant birthweight. STUDY DESIGN: This is a prospective study of 479 healthy, non-diabetic mother and infant pairs attending the National Maternity Hospital in Ireland. Fasting glucose was measured in early pregnancy (11.8+/-2.3 weeks). At 28 weeks gestation a repeat fasting glucose was measured and 1h glucose challenge testing (1h GCT) was performed. At 34 weeks' gestation (33+5-34+5 weeks) fetal growth and fetal anterior abdominal wall width, a marker of fetal adiposity, were measured. At delivery cord glucose was measured and neonatal anthropometry recorded. RESULTS: There was a positive correlation between fasting glucose concentration during pregnancy and both infant birthweight and fetal anterior abdominal wall width at 34 weeks gestation. The incidence of macrosomia (birthweight>4.5kg) was significantly greater for maternal and cord blood glucose levels in the highest quartile compared to the lowest quartile (20.7% vs. 11.7%, p<0.05 in the first trimester, 21.3% vs. 7.2%, p<0.05, at 28 weeks, and 33.3% vs. 10%, p<0.05, in cord blood). Maternal glucose concentrations at each time point, though not cord glucose, were related to early pregnancy maternal body mass index (r=0.19, p<0.001 in first trimester, r=0.25, p<0.001 at 28 weeks, r=0.15, p<0.01 with 1h GCT). CONCLUSION: Maternal glucose homeostasis is an important determinant of fetal size. We have shown that even small variations in fasting glucose concentrations can influence fetal growth and adiposity. This effect is seen from the first trimester and maintained until delivery. PMID- 21982557 TI - Remarkable changes in the choice of timing to discuss organ donation with the relatives of a patient: a study in 228 organ donations in 20 years. AB - INTRODUCTION: We studied whether the choice of timing of discussing organ donation for the first time with the relatives of a patient with catastrophic brain injury in The Netherlands has changed over time and explored its possible consequences. Second, we investigated how thorough the process of brain death determination was over time by studying the number of medical specialists involved. And we studied the possible influence of the Donor Register on the consent rate. METHODS: We performed a retrospective chart review of all effectuated brain dead organ donors between 1987 and 2009 in one Dutch university hospital with a large neurosurgical serving area. RESULTS: A total of 271 medical charts were collected, of which 228 brain dead patients were included. In the first period, organ donation was discussed for the first time after brain death determination (87%). In 13% of the cases, the issue of organ donation was raised before the first EEG. After 1998, we observed a shift in this practice. Discussing organ donation for the first time after brain death determination occurred in only 18% of the cases. In 58% of the cases, the issue of organ donation was discussed before the first EEG but after confirming the absence of all brain stem reflexes, and in 24% of the cases, the issue of organ donation was discussed after the prognosis was deemed catastrophic but before a neurologist or neurosurgeon assessed and determined the absence of all brain stem reflexes as required by the Dutch brain death determination protocol. CONCLUSIONS: The phases in the process of brain death determination and the time at which organ donation is first discussed with relatives have changed over time. Possible causes of this change are the introduction of the Donor Register, the reintroduction of donation after circulatory death and other logistical factors. It is unclear whether the observed shift contributed to the high refusal rate in The Netherlands and the increase in family refusal in our hospital in the second studied period. Taking published literature on this subject into account, it is possible that this may have a counterproductive effect. PMID- 21982559 TI - Methylation changes associated with early maturation stages in the Atlantic salmon. AB - BACKGROUND: Early maturation in the Atlantic salmon is an interesting subject for numerous research lines. Prior to sea migration, parr can reach sexual maturation and successfully fertilize adult female eggs during the reproductive season. These individuals are known as precocious parr, mature parr or "sneakers". Reasons for early maturation are unknown and this transitory stage is usually considered to be a threshold trait. Here, we compare methylation patterns between mature and immature salmon parr from two different rivers in order to infer if such methylation differences may be related to their maturation condition. First we analyzed genetic differences between rivers by means of AFLPs. Then, we compared the DNA methylation differences between mature and immature parrs, using a Methylation-Sensitive Amplified Polymorphism (MSAP), which is a modification of the AFLPs method by making use of the differential sensitivity of a pair of restriction enzymes isoschizomeres to cytosine methylation. The tissues essayed included brain, liver and gonads. RESULTS: AFLPs statistical analysis showed that there was no significant differentiation between rivers or a significant differentiation between maturation states in each river. MSAP statistical analysis showed that among the three tissues sampled, the gonads had the highest number of significant single-locus variation among populations with 74 loci followed by brain with 70 and finally liver with only 12. Principal components analysis (PCA) of the MSAP profiles revealed different profiles among different tissues (liver, brain and testis) clearly separating maturation states in the testis tissue when compared to the liver. CONCLUSIONS: Our results reveal that genetically-similar mature and immature salmon parr present high levels of DNA methylation variation in two of the three analyzed tissues. We hypothesize that early maturation may be mostly mediated by epigenetic processes rather than by genetic differences between parrs. To our knowledge this is the first study that attempt to link phenotypic plasticity in salmonids and epigenetic changes. PMID- 21982558 TI - Toll-like receptors in cerebral ischemic inflammatory injury. AB - Cerebral ischemia triggers acute inflammation, which has been associated with an increase in brain damage. The mechanisms that regulate the inflammatory response after cerebral ischemia are multifaceted. An important component of this response is the activation of the innate immune system. However, details of the role of the innate immune system within the complex array of mechanisms in cerebral ischemia remain unclear. There have been recent great strides in our understanding of the innate immune system, particularly in regard to the signaling mechanisms of Toll-like receptors (TLRs), whose primary role is the initial activation of immune cell responses. So far, few studies have examined the role of TLRs in cerebral ischemia. However, work with experimental models of ischemia suggests that TLRs are involved in the enhancement of cell damage following ischemia, and their absence is associated with lower infarct volumes. It may be possible that therapeutic targets could be designed to modulate activities of the innate immune system that would attenuate cerebral brain damage. Ischemic tolerance is a protective mechanism induced by a variety of preconditioning stimuli. Interpreting the molecular mechanism of ischemic tolerance will open investigative avenues into the treatment of cerebral ischemia. In this review, we discuss the critical role of TLRs in mediating cerebral ischemic injury. We also summarize evidence demonstrating that cerebral preconditioning downregulates pro-inflammatory TLR signaling, thus reducing the inflammation that exacerbates ischemic brain injury. PMID- 21982560 TI - PAH biomarkers in common eelpout (Zoarces viviparus) from Danish waters. AB - Eelpouts (Zoarces viviparus) sampled at surveillance stations during the fall of 2007 and spring 2008 in different Danish coastal areas, were studied for biomarkers of polycyclic aromatic hydrocarbons (PAHs) exposure and effects. Two analytical techniques, synchronous fluorescence spectrometry (SFS) and high performance liquid chromatography with fluorescence detection (HPLC/F), were applied for detecting PAH metabolites in bile and urine. CYP1A activity, in this study regarded as potential biomarker of effect, was measured as 7 ethoxyresorufin-O-deethylase (EROD) activity in liver of eelpouts from different stations. Biliary PAH metabolite measurements were used for monitoring the environmental PAH load at the surveillance stations. There was found significant difference in biliary PAH metabolite content between sexes with male fish containing higher concentrations of PAH metabolites than females. The urinary PAH metabolite content did not show the same spatial trends as biliary PAH metabolites. However, fish from Aarhus Bight and Vejle Fjord had significantly higher levels of PAH metabolites in both urine and bile compared to the reference station Agerso. Normalisation methods applied for bile and urine matrices did not have any effect or only slightly reduced the coefficients of variation in data sets. The CYP1A activity in eelpout liver did not show the same spatial distribution trends between sampling sites as did biliary or urinary PAH metabolite contents. Male eelpouts showed significantly higher CYP1A activity than females in fall sampling period but there were no differences found in the spring period. General comparison between both seasons showed that eelpouts sampled in the fall had significantly higher CYP1A activity than fish sampled during spring season. Overall, the results of this study describe selected biomarker responses in eelpouts to environmental PAH load at the different areas along Danish coasts. PMID- 21982561 TI - Rhodotorula species infection in traumatic keratitis--a case report. AB - We report a case of keratitis due to Rhodotorula species in an agricultural worker following trauma with sugarcane leaf. There are very few cases of Rhodotorula infection in corneal grafts following lamellar keratoplasty. This is a unique case reporting Rhodotorula infection after traumatic corneal ulcer. PMID- 21982562 TI - The outpatient institutional antibiogram does not accurately reflect the susceptibility of prepartum group B streptococcal isolates to erythromycin and clindamycin. AB - This study compared the antimicrobial susceptibilities of 100 nonduplicate group B streptococcal (GBS) isolates from screening cultures of women attending OB-GYN clinics to a similar number of outpatient infection isolates recorded on the institutional antibiogram of a university teaching hospital. The screening GBS isolates were significantly more susceptible to erythromycin (72% versus 45%) and clindamycin (77% versus 48%) than the infection isolates. PMID- 21982563 TI - Surveillance of JNJ-Q2 activity tested against Staphylococcus aureus and beta hemolytic streptococci as a component of the 2010 SENTRY Antimicrobial Surveillance Program. AB - JNJ-Q2 is a novel broad-spectrum bactericidal fluorinated 4-quinolone with potent activity against Gram-positive and -negative pathogens with a balanced potency against both DNA gyrase and topoisomerase IV targets. JNJ-Q2 is in clinical development for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) and community-acquired bacterial pneumonia. With the use of reference broth microdilution methods in a central reference laboratory design, MIC values were obtained for 3650 pathogens (44.4% were from patients diagnosed with ABSSSI) obtained during the 2010 SENTRY antimicrobial surveillance program. Isolates were collected from patients in 96 medical centers in 26 countries in North America, Europe, Latin America, and Asia Pacific. JNJ-Q2 demonstrated good activity overall (MIC(50/90), 0.015/0.5 MUg/mL) and against 3081 Staphylococcus aureus with >95% of the isolates inhibited at a MIC of <=0.5 MUg/mL; against 1410 levofloxacin-resistant Staphylococcus aureus isolates, >90% were inhibited by MIC <=0.5 MUg/mL. All isolates were inhibited at a MIC of <=2 MUg/mL. In addition, JNJ-Q2 demonstrated excellent activity (MIC(90), 0.015 MUg/mL) against 569 isolates of beta-hemolytic streptococci (including 278 Streptococcus pyogenes and 161 Streptococcus agalactiae). JNJ-Q2 was the most potent fluoroquinolone tested overall and against all pathogens when compared directly to moxifloxacin, levofloxacin, and ciprofloxacin. PMID- 21982564 TI - Development of a diagnostic multiplex polymerase chain reaction microarray assay to detect and differentiate Brucella spp. AB - Brucellosis is a worldwide zoonosis leading to tremendous economic losses and severe human illness. Fast and reliable laboratory tests are needed to detect disease in both humans and animals and to monitor the production of safe food products and feed. For rapid identification of the genus Brucella and differentiation of its species, a multiplex polymerase chain reaction microarray assay based on 11 signature sequences and redundant oligonucleotide probes was developed. The gene targets included genus-specific sequences in bcsp31, perA, cgs, and omp2b, as well as chromosomal regions displaying species-specific hybridization patterns. Brucella reference strains and a representative panel of 102 field isolates were unambiguously identified by their hybridization patterns. The differentiation of species, however, was limited in members of the groups B. suis bv 3/4/B. canis and B. neotomae/B. microti. In summary, the newly developed Brucella ArrayTube(r) assay is an easy-to-handle molecular test for high throughput and parallel analysis. PMID- 21982565 TI - Development of new radiopharmaceuticals for imaging monoamine oxidase B. AB - INTRODUCTION: Imaging monoamine oxidase B (MAO-B) in the central nervous system with PET is an important goal for psychiatric studies. We here report an improved and automated radiosynthesis of N-(6-[(18)F]-fluorohexyl)-N-methylpropargylamine ([(18)F]FHMP; [(18)F]-1), as well as the radiosynthesis of two new promising candidates for imaging cerebral MAO-B, namely, carbon-11-labeled 3-(4-[(11)C] methoxyphenyl)-6-methyl-2H-1-benzopyran-2-one ([(11)C]-2) and N-((1H-pyrrol-2 yl)methyl)-N-[(11)C]-methyl-1-phenylmethanamine ([(11)C]-3). METHODS: Fluorine-18 labeled 1 was prepared via a tosyloxy precursor in 29%+/-5% uncorrected radiochemical yield, relative to [(18)F]-fluoride. Both carbon-11-labeled compounds were prepared with [(11)C]CH(3)I using the "LOOP" method in 11% and 18% uncorrected radiochemical yields, respectively, relative to starting [(11)C]CO(2). All radiotracers had specific activities >37 GBq/MUmol and were >98% radiochemically pure at end of synthesis (<40 min). All radiotracers were evaluated by ex vivo biodistribution studies in conscious rodents. RESULTS: A major radioactive metabolite in the rodent brain was observed following administration of [(18)F]-1. While [(11)C]-2 had moderate brain penetration and good clearance from normal brain tissue, distribution of radioactivity in brain was indicative of free and nonspecific binding. Good brain uptake was observed with [(11)C]-3 (0.8%-1.4% injected dose per gram at 5 min postinjection), binding appeared to be reversible and distribution conformed with regional distribution of MAO-B in the rat brain. Preinjection of 3 or L-deprenyl showed a modest reduction (up to 25%) of brain activity. CONCLUSION: Carbon-11-labeled 3 was found to have the most favorable properties of the radiotracers evaluated; however, the signal-to-noise ratio was too low to warrant further in vivo imaging studies. Alternative radiotracers for imaging MAO-B are under development. PMID- 21982566 TI - Evaluation of striatal oxidative stress in patients with Parkinson's disease using [62Cu]ATSM PET. AB - INTRODUCTION: To clarify the role of oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson's disease (PD) in living patients, positron emission tomography (PET) with [(62)Cu]diacetyl-bis(N(4) methylthiosemicarbazone) ([(62)Cu]ATSM) was applied to functional imaging of oxidative stress mainly due to mitochondrial dysfunction in the striata of patients with PD. METHODS: Fifteen PD patients who presented with lateral dominant symptoms at onset and six healthy controls underwent [(62)Cu]ATSM PET. Dynamic PET data acquisition was performed, and standardized uptake values (SUVs) were obtained from the delayed phase of dynamic data by means of region of interest analysis. The striatum-to-cerebellum SUV ratio (S/C ratio) was calculated from the SUV in all subjects of the striatum and the cerebellar cortex. RESULTS: The mean S/C ratio of the bilateral striata of the patients (1.15+/-0.10) was significantly increased compared with that of the controls (1.08+/-0.02) (P<.05). In the patients, the S/C ratio of the bilateral striata showed a positive correlation with the Unified Parkinson's Disease Rating Scale (UPDRS) rating (r=0.52, P<.05), and the S/C ratio of the striatum contralateral to the initially affected body side showed a strong positive correlation with the UPDRS rating (r=0.62, P<.05). CONCLUSIONS: [(62)Cu]ATSM PET imaging demonstrated that striatal oxidative stress was enhanced in PD patients compared with the controls and increased with the progression of disease severity, particularly in the contralateral striatum. These findings indicated that oxidative stress associates with striatal neurodegeneration in PD. PMID- 21982567 TI - Comparisons of [18F]-1-deoxy-1-fluoro-scyllo-inositol with [18F]-FDG for PET imaging of inflammation, breast and brain cancer xenografts in athymic mice. AB - INTRODUCTION: The aim of the study was to evaluate the uptake of [(18)F]-1-deoxy 1-fluoro-scyllo-inositol ([(18)F]-scyllo-inositol) in human breast cancer (BC) and glioma xenografts, as well as in inflammatory tissue, in immunocompromised mice. Studies of [(18)F]-2-fluoro-2-deoxy-d-glucose ([(18)F]-FDG) under the same conditions were also performed. METHODS: Radiosynthesis of [(18)F]-scyllo inositol was automated using a commercial synthesis module. Tumour, inflammation and normal tissue uptakes were evaluated by biodistribution studies and positron emission tomography (PET) imaging using [(18)F]-scyllo-inositol and [(18)F]-FDG in mice bearing subcutaneous MDA-MB-231, MCF-7 and MDA-MB-361 human BC xenografts, intracranial U-87 MG glioma xenografts and turpentine-induced inflammation. RESULTS: The radiosynthesis of [(18)F]-scyllo-inositol was automated with good radiochemical yields (24.6%+/-3.3%, uncorrected for decay, 65+/-2 min, n=5) and high specific activities (>=195 GBq/MUmol at end of synthesis). Uptake of [(18)F]-scyllo-inositol was greatest in MDA-MB-231 BC tumours and was comparable to that of [(18)F]-FDG (4.6+/-0.5 vs. 5.5+/-2.1 %ID/g, respectively; P=.40), but was marginally lower in MDA-MB-361 and MCF-7 xenografts. Uptake of [(18)F]-scyllo-inositol in inflammation was lower than [(18)F]-FDG. While uptake of [(18)F]-scyllo-inositol in intracranial U-87 MG xenografts was significantly lower than [(18)F]-FDG, the tumour-to-brain ratio was significantly higher (10.6+/-2.5 vs. 2.1+/-0.6; P=.001). CONCLUSIONS: Consistent with biodistribution studies, uptake of [(18)F]-scyllo-inositol was successfully visualized by PET imaging in human BC and glioma xenografts, with lower accumulation in inflammatory tissue than [(18)F]-FDG. The tumour-to-brain ratio of [(18)F]-scyllo-inositol was also significantly higher than that of [(18)F]-FDG for visualizing intracranial glioma xenografts in NOD SCID mice, giving a better contrast. PMID- 21982568 TI - Factors influencing the uptake of 18F-fluoroestradiol in patients with estrogen receptor positive breast cancer. AB - INTRODUCTION: (18)F-Fluoroestradiol (FES) PET imaging provides a non-invasive method to measure estrogen receptor (ER) expression in tumors. Assessment of factors that could affect the quantitative level of FES uptake is important as part of the validation of FES PET for evaluating regional ER expression in breast cancer. METHODS: This study examines FES uptake in tumors from 312 FES PET scans (239 patients) with documented ER+ primary breast cancer. FES uptake was compared to clinical and laboratory data, treatment prior to or at time of scan, and properties of FES and its metabolism and transport. Linear mixed models were used to explore univariate, threshold-based and multivariate associations. RESULTS: Sex hormone-binding globulin (SHBG) was inversely associated with FES SUV. Average FES uptake did not differ by levels of plasma estradiol, age or rate of FES metabolism. FES tumor uptake was greater for patients with a higher body mass index (BMI), but this effect did not persist when SUV was corrected for lean body mass (LBM). In multivariate analysis, only plasma SHBG binding was an independent predictor of LBM-adjusted FES SUV. CONCLUSIONS: Calculation of FES SUV, possibly adjusted for LBM, should be sufficient to assess FES uptake for the purpose of inferring ER expression. Pre-menopausal estradiol levels do not appear to interfere with FES uptake. The availability and binding properties of SHBG influence FES uptake and should be measured. Specific activity did not have a clear influence on FES uptake, except perhaps at higher injected mass per kilogram. These results suggest that FES imaging protocols may be simplified without sacrificing the validity of the results. PMID- 21982569 TI - The role of nucleoside/nucleotide transport and metabolism in the uptake and retention of 3'-fluoro-3'-deoxythymidine in human B-lymphoblast cells. AB - INTRODUCTION: Recent studies in the human adenocarcinoma cell line A549 have identified cell growth-dependent equilibrative nucleoside transporter-1 (hENT1) as a modifier of 3'-fluoro-3'-deoxythymidine (FLT) uptake and retention. In the present study, we used the ability to isolate human lymphoblastoid clones deficient in thymidine kinase 1 (TK1) to study how metabolism and nucleoside transport influence FLT uptake and retention. METHODS: Transport and metabolism of FLT were measured in the human lymphoblastoid cell line TK6 and in eight clones isolated from TK6. Four clones were TK1-proficient, while four were TK1 deficient. Both influx and efflux of FLT were measured under conditions where concentrative and equilibrative transport could be distinguished. RESULTS: Sodium dependent concentrative FLT transport dominated over equilibrative transport mechanisms and while inhibition of hENT1 reduced FLT uptake, there were no correlations between clonal variations in hENT1 levels and FLT uptake. There was an absolute requirement of TK1 for concentration of FLT in TK6 cells. FLT uptake reached a peak after 60 min of incubation with FLT after which intracellular levels of FLT and FLT metabolites declined. Efflux was rapid and was associated with reductions in FLT and each of its metabolites. Both FLT and FLT monophosphate were found in the efflux buffer. CONCLUSIONS: Initial rates of FLT uptake were a function of both concentrative and equilibrative transporters. TK1 activity was an absolute requirement for the accumulation of FLT. Retention was dependent on nucleoside/nucleotide efflux and retrograde metabolism of FLT nucleotides. PMID- 21982570 TI - Evaluation of F-18-labeled 5-iodocytidine (18F-FIAC) as a new potential positron emission tomography probe for herpes simplex virus type 1 thymidine kinase imaging. AB - OBJECTIVE: Herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene in combination with radiolabeled nucleoside substrates is the most widely used reporter system. This study characterized 1-(2'-deoxy-2'-[(18)F]fluoro-beta-D arabinofuranosyl)-5-iodocytosine ((18)F-FIAC) as a new potential positron emission tomography (PET) probe for HSV1-tk gene imaging and compared it with 2' deoxy-2'-[(18)F]fluoro-5-iodo-1-beta-D-arabinofuranosyluracil ((18)F-FIAU) and 2' deoxy-2'-[(18)F]fluoro-5-ethyl-1-beta-D-arabinofuranosyluracil((18)F-FEAU) (thymidine analogues) in an NG4TL4-WT/STK sarcoma-bearing mouse model. METHODS: A cellular uptake assay, biodistribution study, radioactive metabolites assay and microPET imaging of NG4TL4-WT/STK tumor-bearing mice post administration of (18)F FIAC, (18)F-FIAU and (18)F-FEAU were conducted to characterize the biological properties of these tracers. RESULTS: Highly specific uptake of (18)F-FIAC, (18)F FIAU and (18)F-FEAU in tk-transfected [tk(+)] cells was observed. The tk(+)-to tk(-) cellular uptake ratio after a 2-h incubation was 66.6+/-25.1, 76.3+/-18.2 and 247.2+/-37.2, respectively. In biodistribution studies, (18)F-FIAC showed significant tk(+) tumor specificity (12.6; expressed as the tk(+)-to-tk(-) tumor uptake ratio at 2 h postinjection) comparable with (18)F-FIAU (15.8) but lower than (18)F-FEAU (48.0). The results of microPET imaging also revealed the highly specific accumulation of these three radioprobes in the NG4TL4-tk(+) tumor. CONCLUSION: Our findings suggested that the cytidine analogue (18)F-FIAC is a new potential PET probe for the imaging of HSV1-tk gene expression. (18)F-FIAC may be regarded as the prodrug of (18)F-FIAU in vivo. PMID- 21982571 TI - PEGylation of (99m)Tc-labeled bombesin analogues improves their pharmacokinetic properties. AB - INTRODUCTION: Radiolabeled bombesin (BN) conjugates are promising radiotracers for imaging and therapy of breast and prostate tumors in which BN(2)/gastrin releasing peptide (GRP) receptors are overexpressed. However, the low in vivo stability of BN conjugates may limit their clinical application. In an attempt to improve their pharmacokinetics and counteract their rapid enzymatic degradation, we prepared a series of polyethylene glycol (PEG)-ylated BN(7-14) analogues for radiolabeling with (99m)Tc(CO)(3) and evaluated them in vitro and in vivo. METHODS: Derivatization of a stabilized (N(alpha)His)Ac-BN(7-14)[Cha(13),Nle(14)] analogue with linear PEG molecules of various sizes [5 kDa (PEG(5)), 10 kDa (PEG(10)) and 20 kDa (PEG(20))] was performed by PEGylation of the E-amino group of a beta(3)hLys-betaAla-betaAla spacer between the stabilized BN sequence and the (N(alpha)His)Ac chelator. The analogues were then radiolabeled by employing the (99m)Tc-tricarbonyl technique. Binding affinity and internalization/externalization studies were performed in vitro in human prostate carcinoma PC-3 cells. Stability was investigated in vitro in human plasma and in vivo in Balb/c mice. Finally, single photon emission computed tomography (SPECT)/X-ray computed tomography studies were performed in nude mice bearing PC 3 tumor xenografts. RESULTS: PEGylation did not affect the binding affinity of BN analogues, as the binding affinity for BN(2)/GRP receptors remained high (K(d)<0.9 nM). However, in vitro binding kinetics of the PEGylated analogues were slower. Steady-state condition was reached after 4 h, and the total cell binding was 10 times lower than that for the non-PEGylated counterpart. Besides, PEGylation improved the stability of BN conjugates in vitro and in vivo. The BN derivative conjugated with a PEG(5) molecule showed the best pharmacokinetics in vivo, i.e., faster blood clearance and preferential renal excretion. The tumor uptake of the (99m)Tc-PEG(5)-Lys-BN conjugate was slightly higher compared to that of the non-PEGylated analogue (3.91%+/-0.44% vs. 2.80%+/-0.28% injected dose per gram 1 h postinjection, p.i.). Tumor retention was also increased, resulting in a threefold higher amount of radioactivity in the tumor at 24 h p.i. Furthermore, decreased hepatobiliary excretion and increased tumor-to-nontarget ratios (tumor-to-blood: 17.1 vs. 2.1; tumor-to-kidney: 1.1 vs. 0.4; tumor-to liver: 5.8 vs. 1.0, 24 h p.i.) were observed and further confirmed via small animal SPECT images 1 h p.i. CONCLUSION: PEGylation proved to be an effective strategy to enhance the tumor-targeting potential of (99m)Tc-labeled BN-based radiopharmaceuticals and probably other radiolabeled peptides. PMID- 21982572 TI - Synthesis and evaluation of a novel 68Ga-chelate-conjugated bisphosphonate as a bone-seeking agent for PET imaging. AB - INTRODUCTION: (68)Ga is a positron-emitting nuclide that has significant imaging potential given that, unlike cyclotron-produced (18)F, the isotope can be produced on-site utilizing a (68)Ge/(68)Ga generator. We recently synthesized a novel bone-seeking agent by coupling a bisphosphonate with the (68)Ga chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). This study presents a first report on the potential of this (68)Ga bone-seeking radiopharmaceutical in the detection of bone metastases. METHODS: 4-Amino-1-hydroxybutylidene-1,1 bisphosphonate was conjugated with 2-[4,7-di(carboxymethyl)-1,4,7-triazonan-1 yl]pentanedioic acid, yielding 2-[4,7-di(carboxymethyl)-1,4,7-triazonan-1-yl]-5 [(4-hydroxy-4,4-diphosphonobutyl)amino]-5-oxopentanoic acid (NOTA-BP). (68)Ga labeled NOTA-BP ([(68)Ga]NOTA-BP) was prepared by complexation of NOTA-BP with [(68)Ga] gallium chloride and evaluated in in vitro experiments, biodistribution experiments and micro-positron emission tomography (PET) imaging experiments. RESULTS: The labeling of NOTA-BP with (68)Ga was completed by heating for 10 min. [(68)Ga]NOTA-BP was determined to have a radiochemical purity of over 95%, a high affinity for hydroxyapatite and a high stability in plasma. In in vivo biodistribution experiments, [(68)Ga]NOTA-BP demonstrated high bone uptake potential. Compared with (99m)Tc-labeled methylene diphosphonate ([(99m)Tc]MDP) and [(18)F]fluoride, [(68)Ga]NOTA-BP exhibited faster blood clearance and a higher bone-to-blood ratio. In addition, mouse model bone metastasis was detected by micro-PET imaging at 1 h postinjection of [(68)Ga]NOTA-BP. CONCLUSION: We have developed a novel (68)Ga-radiolabeled bone-seeking agent. This [(68)Ga]NOTA-BP complex was found to have a high bone affinity and rapid blood clearance, and may thus prove to be useful as a bone-seeking agent for clinical PET. PMID- 21982573 TI - Rapid synthesis and in vitro and in vivo evaluation of folic acid derivatives labeled with fluorine-18 for PET imaging of folate receptor-positive tumors. AB - In an attempt to visualize folate receptors that overexpress on many cancers, [(18)F]-fluorobenzene and pyridinecarbohydrazide-folate/methotrexate conjugates ([(18)F]-1, [(18)F]-2-folates and [(18)F]-8, [(18)F]-9-MTXs) were synthesized by the nucleophilic displacement reactions using ethyl-trimethylammonium-benzoate and pyridinecarboxylate precursors. The intermediates ethyl [(18)F]-fluorinated benzene and pyridine esters were reacted with hydrazine to produce the [(18)F] fluorobenzene and pyridinecarbohydrazides, followed by coupling with N hydroxysuccinimide-folate/MTX. Radiochemical yields were greater than 80% (decay corrected), with total synthesis time of less than 45 min. Radiochemical purities were always greater than 97% without high-performance liquid chromatography purification. These synthetic approaches hold considerable promise as rapid and simple method for the radiofluorination of folate derivatives with high radiochemical yield in short synthesis time. In vitro tests on KB cell line showed that significant amount of the radioconjugates were associated with cell fractions, and in vivo characterization in normal Balb/c mice revealed rapid blood clearance of these radioconjugates with excretion predominantly by the urinary and partially by the hepatobiliary systems. Biodistribution studies in nude mice bearing human KB cell line xenografts demonstrated significant tumor uptake and favorable biodistribution profile for [(18)F]-2-folate over the other conjugates. The uptake in the tumors was blocked by excess coinjection of folic acid, suggesting a receptor-mediated process. Micro-positron emission tomography images of nude mice bearing human KB cell line xenografts confirmed these observations. These results demonstrate that [(18)F]-2-folate may be useful as molecular probe for detecting and staging of folate receptor-positive cancers, such as ovarian cancer and their metastasis as well as monitoring tumor response to treatment. PMID- 21982574 TI - Sigma receptor binding of tetrabenazine series tracers targeting VMAT2 in rat pancreas. AB - The vesicular monoamine transporter type II (VMAT2) is highly expressed in pancreatic beta-cells and thus has been proposed to be a potential target for measuring beta-cell mass (BCM) by molecular imaging. Several tracers based on the TBZ backbone, including 9-fluoropropyl-(+)-dihydrotetrabenazine ([(18)F]AV-133), have shown some promising results as potential biomarkers for BCM despite a relatively high background signal in the pancreas. In the present study, we explore the background binding characteristics of [(18)F]AV-133 in rat pancreas. METHODS: Pancreatic exocrine cells and islet cells were isolated and purified from Sprague-Dawley rats. Membrane homogenates, prepared from both pancreatic exocrine and islet cells as well as from brain striatum regions, were used for in vitro binding studies of [(18)F]AV-133 under a selective masking condition. 1,3 Di-o-tolylguanidine (DTG), displaying high and roughly equal affinity for both sigma-1 and sigma-2 receptors, was chosen at 5 MUM concentration for the masking/blocking studies. RESULTS: [(18)F]AV-133 binding to rat striatum homogenates was not significantly altered by the presence of DTG. In contrast, [(18)F]AV-133 showed significant competition with DTG for binding sites in rat pancreatic exocrine homogenates as well as in rat islet cell homogenates. Importantly, in the presence of DTG, [(18)F]AV-133 showed a single high-affinity binding site on islet cell homogenates with a K(d) value of 3.8 nM which is consistent with the affinity reported previously for VMAT2 sites in rat pancreas. CONCLUSIONS: [(18)F]AV-133, in addition to a high-affinity VMAT2 binding site, binds with low affinity (but high capacity) to sigma components that are present in the rat pancreas. Identification of the cause of background binding of [(18)F]AV-133 to rat pancreatic tissue may lead to improved methods for quantification. PMID- 21982575 TI - Dedifferentiation of differentiated thyroid carcinoma cell line FTC-133 is enhanced by 131I pretreatment. AB - INTRODUCTION: Differentiated thyroid carcinoma (DTC) usually has a high iodine uptake. However, dedifferentiation of DTC with decreased or no radioiodine ((131)I) uptake is observed in clinical practice, with poor prognosis. The aim of this study was to investigate the effects of (131)I radiation on radioiodine uptake (RAIU) and the expression of thyroid-specific molecules. METHODS: FTC-133 cells were treated with (131)I, the dosage dictated by methylthiazol tetrazolium test results and preliminary experiments. The experimental cell group was incubated with (131)I for 48 h and then cultured for 3 months in (131)I-free medium. The control group was set without (131)I. Primary cells were defined as the blank group. Following treatment, RAIU was measured with a gamma counter as the counts/cell number. Na(+)/I(-) symporter (NIS), thyroid-stimulating hormone receptor (TSHR), thyroid peroxidase (TPO) and thyroglobulin (Tg) levels were detected by Western blotting and radioimmunoassay, and their mRNAs were detected by real-time polymerase chain reaction. RESULTS: RAIU of FTC-133 cells decreased gradually after coincubation with (131)I and did not recover even if (131)I was removed. The relative RAIU of the control and experimental groups was 0.567 and 0.182, respectively, a statistically significant difference (P<.01). Expression of NIS, TSHR, TPO and Tg decreased in the experimental group to a statistically significant degree compared to that of controls (P<.05). CONCLUSION: Changes in the mRNA levels were in accordance with the expression of thyroid-specific proteins. Thus, FTC-133 cells undergo dedifferentiation during long-term culture in vitro, and (131)I may promote this progress. PMID- 21982576 TI - Auger electron emitter against multiple myeloma--targeted endo-radio-therapy with 125I-labeled thymidine analogue 5-iodo-4'-thio-2'-deoxyuridine. AB - INTRODUCTION: Multiple myeloma (MM) is a plasma cell malignancy characterized by accumulation of malignant, terminally differentiated B cells in the bone marrow. Despite advances in therapy, MM remains an incurable disease. Novel therapeutic approaches are, therefore, urgently needed. Auger electron-emitting radiopharmaceuticals are attractive for targeted nano-irradiation therapy, given that DNA of malignant cells is selectively addressed. Here we evaluated the antimyeloma potential of the Auger electron-emitting thymidine analogue (125)I labeled 5-iodo-4'-thio-2'-deoxyuridine ([(125)I]ITdU). METHODS: Cellular uptake and DNA incorporation of [(125)I]ITdU were determined in fluorodeoxyuridine pretreated KMS12BM, U266, dexamethasone-sensitive MM1.S and -resistant MM1.R cell lines. The effect of stimulation with interleukin 6 (IL6) or insulin-like growth factor 1 (IGF1) on the intracellular incorporation of [(125)I]ITdU was investigated in cytokine-sensitive MM1.S and MM1.R cell lines. Apoptotic cells were identified using Annexin V. Cleavage of caspase 3 and PARP was visualized by Western blot. DNA fragmentation was investigated using laddering assay. Therapeutic efficiency of [(125)I]ITdU was proven by clonogenic assay. RESULTS: [(125)I]ITdU was shown to be efficiently incorporated into DNA of malignant cells, providing a promising mechanism for delivering highly toxic Auger radiation emitters into tumor DNA. [(125)I]ITdU had a potent antimyeloma effect in cell lines representing distinct disease stages and, importantly, in cell lines sensitive or resistant to the conventional therapeutic agent, but was not toxic for normal plasma and bone marrow stromal cells. Furthermore, [(125)I]ITdU abrogated the protective actions of IL6 and IGF1 on MM cells. [(125)I]ITdU induced massive damage in the DNA of malignant plasma cells, which resulted in efficient inhibition of clonogenic growth. CONCLUSION: These studies may provide a novel treatment strategy for overcoming resistance to conventional therapy in multiple myeloma. PMID- 21982577 TI - Three-dimensional finite element simulation of closed delaminations in composite materials. AB - Early stage delaminations in composite materials tend to be closed at rest. Inspection with traditional linear ultrasonic techniques generally fails to diagnose and locate such imperfections. However, if undetected and left untreated, incipient defects may gradually grow within the material and eventually lead to failure of the component. Kissing bonds or clapping contacts inherently demand a non-linear diagnostic method, applying a finite excitation amplitude that is able to overcome an activation threshold to open and close the contact. In order to obtain a better understanding and analysis of the macroscopic non-linear behavior that can be observed at the component level, we developed and investigated the results of a finite element model for a composite material containing a single circular delamination. The model makes use of local node splitting and the non-linear constitutive behavior is implemented by means of spring-damper elements at the delamination interface. The results of this parametric study allow a better insight in the behavior of the excited delamination in experimental conditions, including the appearance of localized subharmonics and harmonics of the excitation frequency. Based on the developed model, two different detection and localization techniques (using either a single frequency or a sweep excitation) were demonstrated to determine position, shape, depth and orientation of one or multiple delaminations. PMID- 21982578 TI - Modelling the relationship between obesity and mental health in children and adolescents: findings from the Health Survey for England 2007. AB - A number of studies have reported significant associations between obesity and poor psychological wellbeing in children but findings have been inconsistent. METHODS: This study utilised data from 3,898 children aged 5-16 years obtained from the Health Survey for England 2007. Information was available on Body Mass Index (BMI), parental ratings of child emotional and behavioural health (Strengths and Difficulties Questionnaire), self-reported physical activity levels and sociodemographic variables. A multilevel modelling approach was used to allow for the clustering of children within households. RESULTS: Curvilinear relationships between both internalising (emotional) and externalising (behavioural) symptoms and adjusted BMI were observed. After adjusting for potential confounders the relationships between obesity and psychological adjustment (reported externalising and internalising symptoms) remained statistically significant. Being overweight, rather than obese, had no impact on overall reported mental health. 17% of children with obesity were above the suggested screening threshold for emotional problems, compared to 9% of non-obese children. Allowing for clustering and potential confounding variables children classified as obese had an odds ratio (OR) of 2.13 (95% CI 1.39 to 3.26) for being above the screening threshold for an emotional disorder compared to non obese young people. No cross-level interactions between household income and the relationships between obesity and internalising or externalising symptoms were observed. CONCLUSIONS: In this large, representative, UK-based community sample a curvilinear association with emotional wellbeing was observed for adjusted BMI suggesting the possibility of a threshold effect. Further research could focus on exploring causal relationships and developing targeted interventions. PMID- 21982579 TI - Serving bowl selection biases the amount of food served. AB - OBJECTIVE: To determine how common serving bowls containing food for multiple persons influence serving behavior and consumption and whether they do so independently of satiation and food evaluation. METHODS: In this between-subjects experiment, 68 participants were randomly assigned to either a group serving pasta from a large-sized bowl (6.9-L capacity) or a medium-sized bowl (3.8-L capacity). RESULTS: Analysis of covariance showed that when given a large-sized bowl, diners served 77% more pasta (364.0 vs. 205.5 g; P < .01) and felt more satiated (P = .03) compared with diners given a medium-sized bowl, even though the food was not rated tastier or otherwise notable (all P > .32). CONCLUSIONS AND IMPLICATIONS: In contrast to those in studies involving larger-sized plates and spoons, people serving from larger bowls felt more satiated. These findings again highlight the role that external cues play in food consumption and show the importance of considering serving bowl size in nutrition education. PMID- 21982580 TI - The visual attention span deficit in dyslexia is visual and not verbal. AB - The visual attention (VA) span deficit hypothesis of dyslexia posits that letter string deficits are a consequence of impaired visual processing. Alternatively, some have interpreted this deficit as resulting from a visual-to-phonology code mapping impairment. This study aims to disambiguate between the two interpretations by investigating performance in a non-verbal character string visual categorization task with verbal and non-verbal stimuli. Results show that VA span ability predicts performance for the non-verbal visual processing task in normal reading children. Furthermore, VA span impaired dyslexic children are also impaired for the categorization task independently of stimuli type. This supports the hypothesis that the underlying impairment responsible for the VA span deficit is visual, not verbal. PMID- 21982581 TI - Cueing spatial attention through timing and probability. AB - Even when focused on an effortful task we retain the ability to detect salient environmental information, and even irrelevant visual stimuli can be automatically detected. However, to which extent unattended information affects attentional control is not fully understood. Here we provide evidences of how the brain spontaneously organizes its cognitive resources by shifting attention between a selective-attending and a stimulus-driven modality within a single task. Using a spatial cueing paradigm we investigated the effect of cue-target asynchronies as a function of their probabilities of occurrence (i.e., relative frequency). Results show that this accessory information modulates attentional shifts. A valid spatial cue improved participants' performance as compared to an invalid one only in trials in which target onset was highly predictable because of its more robust occurrence. Conversely, cuing proved ineffective when spatial cue and target were associated according to a less frequent asynchrony. These patterns of response depended on asynchronies' probability and not on their duration. Our findings clearly demonstrate that through a fine decision-making, performed trial-by-trial, the brain utilizes implicit information to decide whether or not voluntarily shifting spatial attention. As if according to a cost planning strategy, the cognitive effort of shifting attention depending on the cue is performed only when the expected advantages are higher. In a trade-off competition for cognitive resources, voluntary/automatic attending may thus be a more complex process than expected. PMID- 21982582 TI - Urbanization and physician maldistribution: a longitudinal study in Japan. AB - BACKGROUND: The relative shortage of physicians in Japan's rural areas is an important issue in health policy. In the 1970s, the Japanese government began a policy to increase the number of medical students and to achieve a better distribution of physicians. Beginning in 1985, however, admissions to medical school were reduced to prevent a future oversupply of physicians. In 2007, medical school entrants equaled just 92% of their 1982 peers. The urban annual population growth rate is positive and the rural is negative, a trend that may affect denominator populations and physician distribution. METHODS: Our data cover six time points and span a decade: 1998, 2000, 2002, 2004, 2006, and 2008. The spatial units for analysis are the secondary tier of medical care (STM) as defined by the Medical Service Law and related legislation. We examined trends in the geographic disparities in population and physician distribution among 348 STMs in Japan. We compared populations and the number of physicians per 100,000 populations in each STM. To measure maldistribution quantitatively, we calculated Gini coefficients for physician distribution. RESULTS: Between 1998 and 2008, the total population and the number of practicing physicians for every 100,000 people increased by 0.95% and 13.6%, respectively. However, the inequality of physician distribution remained constant, although small and mostly rural areas experienced an increase in physician to population ratios. In contrast, as the maldistribution of population escalated during the same period, the Gini coefficient of population rose. Although the absolute number of practicing physicians in small STMs decreased, the fall in the denominator population of the STMs resulted in an increase in the number of practicing physicians per population in those located in rural areas. CONCLUSIONS: A policy that increased the number of physicians and the physician to population ratios between 1998 and 2008 in all geographic areas of Japan, irrespective of size, did not lead to a more equal geographical distribution of physicians. The ratios of physicians to population in small rural STMs increased because of concurrent trends in urbanization and not because of a rise in the number of practicing physicians. PMID- 21982583 TI - Salivary cortisol profiles in patients remitted from recurrent depression: one year follow-up of a mindfulness-based cognitive therapy trial. AB - Few studies have examined changes of diurnal cortisol profiles prospectively, in relation to non-pharmacological interventions such as mindfulness-based cognitive therapy (MBCT). Fifty-six patients remitted from recurrent depression (>=3 episodes) were included in an 8-week randomized controlled trial comparing MBCT plus treatment as usual (TAU) with TAU for depression relapse prophylaxis. Saliva samples (0, 15, 30, 45, 60 min post-awakening, 3 PM, 8 PM) were collected on six occasions (pre- and post-intervention, 3-, 6-, 9-, 12-month follow-up). Cortisol awakening response (CAR), average day exposure (AUCday) and diurnal slope were analyzed with mixed effects models (248 profiles, 1-6 per patient). MBCT (n = 28) and TAU groups (n = 28) did not significantly differ with respect to baseline variables. Intra-individual variability exceeded inter-individual variability for the CAR (62.2% vs. 32.5%), AUC(day) (30.9% vs. 23.6%) and diurnal slope (51.0% vs. 34.2%). No time, group and time by group effect was observed for the CAR and diurnal slope. A significant time effect (p = 0.003) was detected for AUCday, which was explained by seasonal variations (p = 0.012). Later wake-up was associated with lower CAR (-11.7% per 1-hour later awakening, p < 0.001) and lower AUCday (-4.5%, p = 0.014). Longer depression history was associated with dampened CAR (-15.2% per 10-year longer illness, p = 0.003) and lower AUCday ( 8.8%, p = 0.011). Unchanged cortisol secretion patterns following participation in MBCT should be interpreted with regard to large unexplained variability, similar relapse rates in both groups and study limitations. Further research is needed to address the scar hypothesis of diminished HPA activity with a longer, chronic course of depression. PMID- 21982584 TI - Ten-year trends in overweight and obesity in the adult Portuguese population, 1995 to 2005. AB - BACKGROUND: There is little information regarding the trends in body mass index (BMI) and obesity in the overall Portuguese population, namely if these trends are similar according to educational level. In this study, we assessed the trends in the prevalence of overweight and obesity in the Portuguese population, overall and by educational level. METHODS: Cross-sectional national health interview surveys conducted in 1995-6 (n = 38,504), 1998-9 (n = 38,688) and 2005-6 (n = 25,348). Data were derived from the population and housing census of 1991 and two geographically-based strata were defined. The sampling unit was the house, and all subjects living in the sampling unit were surveyed. Height and weight were self-reported; the effects of gender, age group and educational level were also assessed by self-reported structured questionnaires. Bivariate comparisons were performed using Chi-square or analysis of variance (ANOVA). Trends in BMI levels were assessed by linear regression analysis, while trends in the prevalence of obesity were assessed by logistic regression. RESULTS: Mean (+/-standard deviation) BMI increased from 25.2 +/- 4.0 in 1995-6 to 25.7 +/- 4.5 kg/m2 in 2005-6. Prevalence of overweight remained stable (36.1% in 1995-6 and 36.4% in 2005) while prevalence of obesity increased (11.5% in 1995-6 and 15.1% in 2005 6). Similar findings were observed according to age group. Mean age-adjusted BMI increase (expressed in kg/m2/year and 95% confidence interval) was 0.073 (0.062, 0.084), 0.016 (0.000, 0.031) and 0.073 (0.049, 0.098) in men with primary, secondary and university levels, respectively; the corresponding values in women were 0.085 (0.073, 0.097), 0.052 (0.035, 0.069) and 0.062 (0.038, 0.084). Relative to 1995-6, obesity rates increased by 48%, 41% and 59% in men and by 40%, 75% and 177% in women with primary, secondary and university levels, respectively. The corresponding values for overweight were 6%, 1% and 23% in men and 5%, 7% and 65% in women. CONCLUSION: Between 1995 and 2005, obesity increased while overweight remained stable in the adult Portuguese population. Although higher rates were found among lesser educated subjects, the strong increase in BMI and obesity levels in highly educated subjects is of concern. PMID- 21982586 TI - Signaling by IL-31 and functional consequences. AB - Cytokines are key to control cellular communication. Interleukin-31 (IL-31) was recently discovered as a new member of the IL-6 family of cytokines. IL-31 signals through a heterodimeric receptor composed of OSMR and IL-31RA, a complex that stimulates the JAK-STAT, the RAS/ERK and the PI3K/AKT signal transduction pathways. The available data suggests that IL-31 is important for both innate and adaptive immunity in tissues that are in close contact with the environment, i.e. the skin, the airways and the lung, and the lining of the intestine. Enhanced expression of IL-31 is associated with a number of diseases, including pruritic diseases such as atopic dermatitis, but also in allergy and inflammatory bowel disease. In these tissues IL-31 coordinates the interaction of different immune cells, including T-cells, mast cells, and eosinophils, with epithelial cells. In this review we have summarized the available data on IL-31 and its receptor, their expression pattern and how they are regulated. We describe the current state of knowledge of the involvement of IL-31 in diseases, both in humans and in mouse models. From these studies it is becoming clear that IL-31 plays an important role in the proper functioning of the skin and of airway and intestinal epithelia. The findings available suggest that IL-31 might be an interesting target for directed drug therapy. PMID- 21982585 TI - Origins of landmark encoding in the brain. AB - The ability to perceive one's position and directional heading relative to landmarks is necessary for successful navigation within an environment. Recent studies have shown that the visual system dominantly controls the neural representations of directional heading and location when familiar visual cues are available, and several neural circuits, or streams, have been proposed to be crucial for visual information processing. Here, we summarize the evidence that the dorsal presubiculum (also known as the postsubiculum) is critically important for the direct transfer of visual landmark information to spatial signals within the limbic system. PMID- 21982587 TI - Cartilage regeneration in SCID mice using a highly organized three-dimensional alginate scaffold. AB - Tissue engineering for cartilage regeneration provides an alternative to surgery for degenerative osteoarthritis. Recently, a highly organized three-dimensional (3D) alginate scaffold was prepared using a microfluidic device; this scaffold is effective for chondrocyte culture in vitro. The performance of this scaffold was further demonstrated; an alginate scaffold seeded with porcine chondrocytes was implanted in the dorsal subcutaneous site of SCID mice. The recipients were sacrificed at 2, 4, and 6 weeks after transplantation. The grafted implants retrieved from the subcutaneous site were analyzed with histologic examinations. Real-time PCR was used to identify the gene expression patterns of the chondrocytes. The hematoxylin and eosin staining showed that the chondrocytes survived normally in SCID mice; cartilage-like structures were formed after 4 weeks implantation. Immunohistochemical staining revealed cells secreted type II collagen, produced glycosaminoglycans (proved by alcian blue stain), and maintained the expression of S-100. On the other hand, the cells were negative for type I and type X collagen staining. PCR showed that the mRNA expressions of aggrecan and type II collagen were up-regulated at weeks two and four, while type I and type X collagen were down-regulated during the study period. In summary, this highly organized 3D alginate scaffold provided a suitable environment and maintained functional phenotypes for chondrocytes in this animal study. PMID- 21982588 TI - Waste management project's alternatives: A risk-based multi-criteria assessment (RBMCA) approach. AB - This paper examines the evaluation of a waste management project's alternatives through a quantitative risk analysis. Cost benefit analysis is a widely used method, in which the investments are mainly assessed through the calculation of their evaluation indicators, namely benefit/cost (B/C) ratios, as well as the quantification of their financial, technical, environmental and social risks. Herein, a novel approach in the form of risk-based multi-criteria assessment (RBMCA) is introduced, which can be used by decision makers, in order to select the optimum alternative of a waste management project. Specifically, decision makers use multiple criteria, which are based on the cumulative probability distribution functions of the alternatives' B/C ratios. The RBMCA system is used for the evaluation of a waste incineration project's alternatives, where the correlation between the criteria weight values and the decision makers' risk preferences is analyzed and useful conclusions are discussed. PMID- 21982589 TI - "Who owns your poop?": insights regarding the intersection of human microbiome research and the ELSI aspects of biobanking and related studies. AB - BACKGROUND: While the social, ethical, and legal implications of biobanking and large scale data sharing are already complicated enough, they may be further compounded by research on the human microbiome. DISCUSSION: The human microbiome is the entire complement of microorganisms that exists in and on every human body. Currently most biobanks focus primarily on human tissues and/or associated data (e.g. health records). Accordingly, most discussions in the social sciences and humanities on these issues are focused (appropriately so) on the implications of biobanks and sharing data derived from human tissues. However, rapid advances in human microbiome research involve collecting large amounts of data on microorganisms that exist in symbiotic relationships with the human body. Currently it is not clear whether these microorganisms should be considered part of or separate from the human body. Arguments can be made for both, but ultimately it seems that the dichotomy of human versus non-human and self versus non-self inevitably breaks down in this context. This situation has the potential to add further complications to debates on biobanking. SUMMARY: In this paper, we revisit some of the core problem areas of privacy, consent, ownership, return of results, governance, and benefit sharing, and consider how they might be impacted upon by human microbiome research. Some of the issues discussed also have relevance to other forms of microbial research. Discussion of these themes is guided by conceptual analysis of microbiome research and interviews with leading Canadian scientists in the field. PMID- 21982590 TI - Metabolomics of aerobic metabolism in mice selected for increased maximal metabolic rate. AB - Maximal aerobic metabolic rate (MMR) is an important physiological and ecological variable that sets an upper limit to sustained, vigorous activity. How the oxygen cascade from the external environment to the mitochondria may affect MMR has been the subject of much interest, but little is known about the metabolic profiles that underpin variation in MMR. We tested how seven generations of artificial selection for high mass-independent MMR affected metabolite profiles of two skeletal muscles (gastrocnemius and plantaris) and the liver. MMR was 12.3% higher in mass selected for high MMR than in controls. Basal metabolic rate was 3.5% higher in selected mice than in controls. Artificial selection did not lead to detectable changes in the metabolic profiles from plantaris muscle, but in the liver amino acids and tricarboxylic acid cycle (TCA cycle) metabolites were lower in high-MMR mice than in controls. In gastrocnemius, amino acids and TCA cycle metabolites were higher in high-MMR mice than in controls, indicating elevated amino acid and energy metabolism. Moreover, in gastrocnemius free fatty acids and triacylglycerol fatty acids were lower in high-MMR mice than in controls. Because selection for high MMR was associated with changes in the resting metabolic profile of both liver and gastrocnemius, the result suggests a possible mechanistic link between resting metabolism and MMR. In addition, it is well established that diet and exercise affect the composition of fatty acids in muscle. The differences that we found between control lines and lines selected for high MMR demonstrate that the composition of fatty acids in muscle is also affected by genetic factors. PMID- 21982591 TI - The tubulin deglutamylase CCPP-1 regulates the function and stability of sensory cilia in C. elegans. AB - BACKGROUND: Posttranslational modifications (PTMs) such as acetylation, detyrosination, and polyglutamylation have long been considered markers of stable microtubules and have recently been proposed to guide molecular motors to specific subcellular destinations. Microtubules can be deglutamylated by the cytosolic carboxypeptidase CCP1. Loss of CCP1 in mice causes cerebellar Purkinje cell degeneration. Cilia, which are conserved organelles that play important diverse roles in animal development and sensation, contain axonemes comprising microtubules that are especially prone to PTMs. RESULTS: Here, we report that a CCP1 homolog, CCPP-1, regulates the ciliary localization of the kinesin-3 KLP-6 and the polycystin PKD-2 in male-specific sensory neurons in C. elegans. In male specific CEM (cephalic sensilla, male) cilia, ccpp-1 also controls the velocity of the kinesin-2 OSM-3/KIF17 without affecting the transport of kinesin-II cargo. In the core ciliated nervous system of both males and hermaphrodites, loss of ccpp-1 causes progressive defects in amphid and phasmid sensory cilia, suggesting that CCPP-1 activity is required for ciliary maintenance but not ciliogenesis. Affected cilia exhibit defective B-tubules. Loss of TTLL-4, a polyglutamylating enzyme of the tubulin tyrosine ligase-like family, suppresses progressive ciliary defects in ccpp-1 mutants. CONCLUSIONS: Our studies suggest that CCPP-1 acts as a tubulin deglutamylase that regulates the localization and velocity of kinesin motors and the structural integrity of microtubules in sensory cilia of a multicellular, living animal. We propose that the neuronal degeneration caused by loss of CCP1 in mammals may represent a novel ciliopathy in which cilia are formed but not maintained, depriving the cell of cilia-based signal transduction. PMID- 21982592 TI - Guarding males protect females from predation in a wild insect. AB - Males frequently remain in close proximity to their mate immediately postcopulation. This behavior has generally been interpreted as a guarding tactic designed to reduce the likelihood that a rival male can rapidly displace the ejaculate of the guarding male [1, 2]. Such attempts by males to control their mates represent a potential source of conflict [3-5], but guarding behaviors in species where it is difficult for males to control their mates suggest that conflict is not inevitable [6, 7]. We employed a network of infrared video cameras to study a wild population of individually marked and genotyped field crickets (Gryllus campestris). Lone females or males suffer similar rates of predation, but when a pair is attacked, the male allows the female priority access to their burrow, and in doing so dramatically increases his probability of being killed. In compensation for this increased predation risk, paired males mate more frequently and father more of the female's offspring. By staying with a male, females increase the sperm contribution of preferred males as well as reducing their predation risk. In contrast to conclusions based on previous lab studies, our field study suggests that mate guarding can evolve in a context of cooperation rather than conflict between the sexes. PMID- 21982593 TI - Pectin-induced changes in cell wall mechanics underlie organ initiation in Arabidopsis. AB - Tissue mechanics have been shown to play a key role in the regulation of morphogenesis in animals [1-4] and may have an equally important role in plants [5-9]. The aerial organs of plants are formed at the shoot apical meristem following a specific phyllotactic pattern [10]. The initiation of an organ from the meristem requires a highly localized irreversible surface deformation, which depends on the demethylesterification of cell wall pectins [11]. Here, we used atomic force microscopy (AFM) to investigate whether these chemical changes lead to changes in tissue mechanics. By mapping the viscoelasticity and elasticity in living meristems, we observed increases in tissue elasticity, correlated with pectin demethylesterification, in primordia and at the site of incipient organs. Measurements of tissue elasticity at various depths showed that, at the site of incipient primordia, the first increases occurred in subepidermal tissues. The results support the following causal sequence of events: (1) demethylesterification of pectin is triggered in subepidermal tissue layers, (2) this contributes to an increase in elasticity of these layers-the first observable mechanical event in organ initiation, and (3) the process propagates to the epidermis during the outgrowth of the organ. PMID- 21982594 TI - Functional analyses of mutants of the central core domain of an Avian Sarcoma/Leukemia Virus integrase. AB - Integrase (IN) is the enzyme responsible for the integration of the retroviral genome into the host cell DNA. Herein, three mutants of conserved residues (V79, S85 and I146) of the central core domain (CCD) of an Avian Sarcoma/Leukemia Virus IN were analyzed in vitro. Our data revealed (i) the inability of S85T mutant to form dimers and tetramers in the absence of DNA and (ii) a slightly reduced ability of V79A IN in tetramers formation. Surprisingly, both mutants were still able to efficiently achieve concerted DNA integration. This could be explained by the ability of the two mutants to form complexes in the presence of DNA. These data suggest a strong structural role of the region encompassing V79 and S85 residues (beta2/beta3 turn-beta3 strands) following binding to viral DNA and highlight the dynamic nature of IN. PMID- 21982595 TI - West Nile virus infection does not induce PKR activation in rodent cells. AB - dsRNA-activated protein kinase (PKR) is activated by viral dsRNAs and phosphorylates eIF2a reducing translation of host and viral mRNA. Although infection with a chimeric West Nile virus (WNV) efficiently induced PKR and eIF2a phosphorylation, infections with natural lineage 1 or 2 strains did not. Investigation of the mechanism of suppression showed that among the cellular PKR inhibitor proteins tested, only Nck, known to interact with inactive PKR, colocalized and co-immunoprecipitated with PKR in WNV-infected cells and PKR phosphorylation did not increase in infected Nck1,2-/- cells. Several WNV stem loop RNAs efficiently activated PKR in vitro but not in infected cells. WNV infection did not interfere with intracellular PKR activation by poly(I:C) and similar virus yields were produced by control and PKR-/- cells. The results indicate that PKR phosphorylation is not actively suppressed in WNV-infected cells but that PKR is not activated by the viral dsRNA in infected cells. PMID- 21982596 TI - Pivotal role of dermal IL-17-producing gammadelta T cells in skin inflammation. AB - Interleukin-23 (IL-23) and CD4(+) T helper 17 (Th17) cells are thought to be critical in psoriasis pathogenesis. Here, we report that IL-23 predominantly stimulated dermal gammadelta T cells to produce IL-17 that led to disease progression. Dermal gammadelta T cells constitutively expressed the IL-23 receptor (IL-23R) and transcriptional factor RORgammat. IL-17 production from dermal gammadelta T cells was independent of alphabeta T cells. The epidermal hyperplasia and inflammation induced by IL-23 were significantly decreased in T cell receptor delta-deficient (Tcrd(-/-)) and IL-17 receptor-deficient (Il17ra(-/ )) mice but occurred normally in Tcra(-/-) mice. Imiquimod-induced skin pathology was also significantly decreased in Tcrd(-/-) mice. Perhaps further promoting disease progression, IL-23 stimulated dermal gammadelta T cell expansion. In psoriasis patients, gammadelta T cells were greatly increased in affected skin and produced large amounts of IL-17. Thus, IL-23-responsive dermal gammadelta T cells are the major IL-17 producers in the skin and may represent a novel target for the treatment of psoriasis. PMID- 21982597 TI - Mast cell interleukin-2 production contributes to suppression of chronic allergic dermatitis. AB - The incidence of chronic allergic dermatitis is rapidly increasing. Regulatory control of this disease has not been adequately explored. Here we report that mast cell-derived interleukin-2 (IL-2) contributes to the suppression of chronic allergic dermatitis. Mice deficient in IL-2 production, or deficient in mast cells (Kit(W-sh/W-sh)), showed exacerbated dermatitis upon repeated oxazolone challenge when compared to their wild-type counterparts. Adoptive transfer of wild-type, but not Il2(-/-), mast cells into Kit(W-sh/W-sh) mice dampened the inflammatory response. During the course of disease, mast cell expansion occurred at the site of inflammation and also in the spleen, where production of IL-2 by mast cells was markedly enhanced. In the absence of mast cell IL-2 production, the ratio of activated to regulatory T cells at the site of inflammation was increased. Thus, MC-derived IL-2 contributes to the maintenance of suppression in chronic allergic skin inflammation. PMID- 21982598 TI - Interleukin-17C promotes Th17 cell responses and autoimmune disease via interleukin-17 receptor E. AB - Although several interleukin-17 (IL-17) family members and their receptors have been recently appreciated as important regulators in inflammatory diseases, the function of other IL-17 cytokines and IL-17 receptor-like molecules is unclear. Here we show that an IL-17 cytokine family member, IL-17C, was induced in a Th17 cell-dependent autoimmune disease and was required for its pathogenesis. IL-17C bound to IL-17RE, a member of IL-17 receptor family whose full-length isoform was selectively expressed in Th17 cells and signaled via an IL-17RA-RE receptor complex and the downstream adaptor Act1. IL-17C-IL-17RE induced the expression of a nuclear IkappaB family member, IkappaBzeta, in Th17 cells to potentiate the Th17 cell response. Thus, our work has identified a cytokine-receptor pair with important function in regulating proinflammatory responses. This pathway may be targeted to treat autoimmune diseases. PMID- 21982600 TI - What is evidence-based dentistry, and do oral infections increase systemic morbidity or mortality? AB - From Celsus' first reports of rubor, calor, dolor, tumor, and functio laesa, has come an understanding of inflammation's manifestations at the organ, tissue, vascular, cellular, genetic, and molecular levels. Molecular medicine now raises the opposite question: can local oral infections and their inflammatory mediators increase systemic morbidity or mortality? From these perspectives we examine the clinical evidence relating caries, periodontal disease, and pericoronitis to systemic disease. Widespread affirmation of an oral-systemic linkage remains elusive, raising sobering cautions. PMID- 21982599 TI - Determination of HCV genotypes and viral loads in chronic HCV infected patients of Hazara Pakistan. AB - Hepatitis C Virus (HCV) genotype and viral load are two significant predictive variables knowledge of which might persuade treatment decisions. The objective of the present study was to identify the distribution of different HCV genotypes circulating in the study area and to estimate viral load in chronically HCV infected patients. Out of total 305 HCV positive patients, 177 (58%) were males and 128 (42%) were females. Frequency breakup of the HCV positive patients was 169, 69, 38 and 29 from Abbottabad, Mansehra, Haripur and Battagram districts respectively. Out of the total 305 tested serum samples, 255 (83.06%) were successfully genotyped whereas 50 (16.4%) samples were found with unclassified genotypes. Among typable genotypes, 1a accounted for 21 (6.8%) 1b for 14 (4.6%), 2a for 4 (1.31%) 3a for 166 (54.42%) and genotype 3b for (8.19%). Twenty five (8.19%) patients were infected with mixed HCV genotypes. Viral load distribution was classified into three categories based on its viral load levels such as low (< 60, 0000 IU/mL), intermediate (60,0000-80,0000 IU/mL) and high (> 80,0000 IU/mL). The baseline HCV RNA Viral load in HCV genotype 3 infected patients was 50 (26.17%), 46 (24.08%) and 95 (49.73%) for low, intermediate and high categories respectively. For genotypes other than 3, these values for low, intermediate and high viral load categories were 50 (43.85), 35 (30.70) and 29 (25.43) respectively. Pre-treatment viral load in patients with untypable genotype was 19 (38.00%), 5 (20.00%) and 11 (44.00%) for low, intermediate and high viral load categories. Viral load distribution was also categorized sex wise; for males it was 58 (32.76%), 26 (14.68%) and 93 (52.54%) whereas for females it was 40 (31.25%), 34 (26.56%) and 54 (42.18%) for low, intermediate and high viral load respectively. In conclusion HCV genotype 3a is the most prevalent genotype circulating in Hazara Division like other parts of pakistan. Pre treatment viral load is significantly high (p 0.014) in patients infected with HCV genotype 3 as compared to other genotypes. PMID- 21982601 TI - What is the role of biofilms in severe head and neck infections? AB - Most infections of the head and neck and virtually all of those encountered in the practice of dentistry are caused by bacteria that are organized into biofilms. A biofilm is a complex, usually multispecies, highly communicative community of bacteria that is surrounded by a polymeric matrix. Treatment of these types of infections with traditional antibiotics alone is ineffective, and surgical removal of diseased tissue is still necessary. PMID- 21982602 TI - Should teeth be extracted immediately in the presence of acute infection? AB - Immediate extraction of teeth in the setting of an acute infection has shown to be beneficial for many reasons. It results in faster resolution of the infection, decreased pain, and earlier return of function and oral intake. The risk of seeding the infection into deeper spaces by performing immediate extraction is low. PMID- 21982603 TI - Should we wait for development of an abscess before we perform incision and drainage? AB - Deep neck infections are infections (either abscess or cellulitis) that are within the potential spaces and fascial planes of the head and neck. Deep neck infections should not be ignored, and no surgeon should underestimate the necessity of appropriate and timely treatment of deep neck infections due to the serious and potentially life-threatening nature of these infections. This article discusses and reviews the literature with regard to a question that has long been debated in the surgical literature, "Should we wait for the development of an abscess before performing incision and drainage?" PMID- 21982604 TI - What are the antibiotics of choice for odontogenic infections, and how long should the treatment course last? AB - In the everyday practice of oral and maxillofacial surgeons, empiric antibiotics are prescribed in the face of uncertainty. Is there a highly resistant organism present? Are the old-line antibiotics no longer effective? Should a broad spectrum antibiotic be used just to cover all the bases in this case? The surprising result of this systematic review is that when combined with appropriate surgery, the usual antibiotics are all effective. Safety and cost become the differentiating factors in this clinical decision. PMID- 21982605 TI - Should prophylactic antibiotics be used for patients having removal of erupted teeth? AB - Generally, antibiotics should not be required before the removal of erupted carious or periodontally involved teeth unless a significant risk of postoperative infection is present. The decision to use prophylactic antibiotics in noninfected cases should also be based on whether patients have any significant medical risk factors that could adversely affect their humoral and cellular defense mechanisms, and whether any systemic risks are associated with the bacteremia that accompanies tooth extraction. This article discusses the various indications for using prophylactic antibiotics in patients having erupted teeth extracted based on a consideration of these factors. PMID- 21982606 TI - Do antibiotics reduce the frequency of surgical site infections after impacted mandibular third molar surgery? AB - Surgical removal of impacted third molars remains the most common procedure performed by oral and maxillofacial surgeons. Given the abundance of host bacteria within the operative sites, surgical site infections are among the most common complications of third molar removal, with an estimated frequency of 1% to 30%. In this setting, significant controversy has surrounded the use of prophylactic antibiotics in the surgical management of impacted third molars. This article provides a comprehensive review of the available data on antibiotic prophylaxis in impacted third molar surgery and offers specific recommendations on antibiotic use. PMID- 21982607 TI - Does the use of prophylactic antibiotics decrease implant failure? AB - The use of prophylactic antibiotics in implant dentistry is controversial. Given the known risks of antibiotic treatment and lack of consensus on using antibiotics at the time of implant insertion, the purpose of this article was to review available studies on use of perioperative prophylactic antibiotics at the time of implant placement and to provide evidence-based recommendations for antibiotic use. The reviewed studies suggest that a single preoperative dose of 2 g amoxicillin 1 hour before implant placement or 1 g amoxicillin 1 hour preoperatively and 500 mg 4 times daily 2 days postoperatively can reduce the rate of implant failure. PMID- 21982608 TI - How can we as dentists minimize our contribution to the problem of antibiotic resistance? AB - More than 30 million pounds of antibiotics are used in the United States per year, more than 90% for nontherapeutic purposes in animals. Environmental contamination by trace amounts of antibiotics and highly resistant bacteria can lead to resistant infections in humans. Oral and maxillofacial infections are largely mediated by biofilms, which are resistant to antibiotics. Primary treatment is surgical debridement, removal of the cause of the infection, and drainage of pus. Current best practices indicate the use of antibiotics as adjunctive therapy to surgery only when regional, distant, or systemic spread of the infection is a significant risk. PMID- 21982609 TI - How can we diagnose and treat osteomyelitis of the jaws as early as possible? AB - Osteomyelitis of the jaws is an uncommon infection of the maxillofacial area. The disease is often difficult to diagnose, and thus delays in treatment are common, increasing its morbidity. The clinical, radiographic, and laboratory findings of the disease; its forms; and treatment modalities are reviewed. Suggestions for contemporary diagnosis and surgical treatment of acute and chronic suppurative osteomyelitis are discussed. PMID- 21982610 TI - Do dental infections really cause central nervous system infections? AB - In the post-World War I antibiotic era, the prevalence of central nervous system (CNS) infections is estimated to be 1 per 100,000 population. The literature is replete with anecdotal case reports of CNS infections of apparent dental etiology. Conversely, it is widely cited that the incidence of CNS infection of dental etiology is only in the range of 1% to 2%. We seek to answer the question if dental infections really cause CNS infections. In this article, we focus on septic cavernous sinus thrombosis and brain abscess and if it is a diagnosis of exclusion or evidence-based. PMID- 21982611 TI - How do we manage oral infections in allogeneic stem cell transplantation and other severely immunocompromised patients? AB - The oral cavity is among the sites in the body most susceptible to infections. In the immunocompetent population these are most frequently localized odontogenic infections caused by bacteria. In severely immunocompromised patients, such as those undergoing allogeneic stem cell transplantation, fungal and viral infections become especially prominent. Infections in this population can present in an unusual fashion, can spread rapidly to other organs in the body, and are more frequently resistant to therapies. This article discusses the current knowledge of the most frequent presentations of infections in this patient population and reviews contemporary approaches to prevention, diagnosis, and management. PMID- 21982612 TI - What are the lessons we can glean from a review of recent closed malpractice cases involving oral and maxillofacial infections? AB - OMS National Insurance Company insures over 4700 oral and maxillofacial surgeons, 83% of the fellows and members of the American Association of Oral and Maxillofacial Surgeons. The company has over 10,000 closed malpractice claims involving oral and maxillofacial surgeons. Data and trends involving infections that developed following elective surgical procedures and trends involving patients with preexisting odontogenic infections with adverse outcomes are well known to the company. Seven percent of the 10,000+ closed claims involve infections. Recognition and diagnosis of the infection leads to appropriate and timely treatment of infections. Delayed recognition, consultation, and referral leads to delay in the institution of appropriate treatment and can lead to adverse outcomes. PMID- 21982613 TI - Oral and maxillofacial infections: 15 unanswered questions. PMID- 21982615 TI - The utility of MRI for the surgical treatment of women with uterine fibroid tumors. AB - Determination of the reasonable treatment options and the appropriate clinical treatment of women with uterine fibroid tumors often depends on the ability of imaging modalities to accurately detect and localize fibroid tumors. Magnetic resonance imaging (MRI) gives the most complete evaluation (sizes, positions, number) of submucous, intramural, and subserosal myomas and is the most sensitive modality for the detection of small fibroid tumors. MRI allows the evaluation of fibroid tumor proximity to the bladder, rectum, and endometrial cavity, helps define what can be expected at surgery, and may help the gynecologist avoid missing fibroid tumors during surgery. MRI can also make the diagnosis of adenomyosis reliably and may be able to identify uterine sarcoma when present. PMID- 21982616 TI - A novel nonsense mutation in the TITF-1 gene in a Japanese family with benign hereditary chorea. AB - A Japanese family with a novel nonsense mutation in the TITF-1 gene (p.Y98X) is described. The proband showed severe generalized chorea, delayed motor development, subnormal intelligence, congenital hypothyroidism, bronchial asthma, and a history of pulmonary infection, all of which are characteristic features of Brain-Thyroid-Lung syndrome. On the other hand, her brother and mother showed a mild benign hereditary chorea (BHC) phenotype with congenital hypothyroidism. Intrafamilial phenotypic variation is common in BHC/Brain-Thyroid-Lung syndrome and suggests the existence of other genetic or environmental factors regulating TITF-1 function. Although choreic movement in BHC/Brain-Thyroid-Lung syndrome is recognized as non-progressive, the proband showed re-exacerbation of choreic movement at puberty. The dopamine agonist, ropinirole hydrochloride, reduced her choreic movements, suggesting that levodopa and/or dopamine agonists may compensate for underdeveloped dopaminergic pathways in this disorder. PMID- 21982617 TI - POEMS syndrome with prominent acute axonal lesions. AB - Polyneuropathy is a common presenting component of POEMS syndrome whose symptoms are attributed to an overproduction of vascular endothelial growth factor (VEGF). We report two female patients with POEMS syndrome presenting as a severe predominantly axonal neuropathy. A nerve biopsy was performed for these patients; pathological data confirmed unusual numerous acute axonal lesions associated with other classical signs of POEMS syndrome. POEMS syndrome is usually associated with demyelinating neuropathy (and secondary axonal loss); however, prominent axonal neuropathy (with acute axonal lesions on nerve biopsy) can also be observed in this disease. These observations illustrate the heterogeneity of peripheral nervous system involvement in POEMS syndrome. PMID- 21982618 TI - An ecological study of industry in a high-risk region of multiple sclerosis. AB - The county of Varmland, Sweden, has shown a high frequency of multiple sclerosis in several investigations. It has been presented in three studies; a period prevalence study in 1925-1934, a mortality study during 1952-1992 and a prevalence investigation in 2002. The aim of this study was to investigate the pattern of industry in this high-risk area for multiple sclerosis. The three investigations were correlated with industry in 1913 and in the 1950s, all analyzed by the Kruskall-Wallis test. Select industries from wood-pulp, paper and iron/mechanical sectors were tested also in whole Sweden. The Spearman rank correlation was used for these data and forestry data in Varmland. In Varmland, industrial data from 1913 revealed that large sawmills were associated with the period prevalence in 1925-1934 and there was a possible correlation with the prevalence for 2002. Wood-pulp factories showed a possible association with the prevalence 1925-1934 and the mortality 1952-1992. Some industries in the 1950s were correlated with the prevalence 2002. Wood and paper industries in Sweden 1913 showed an association with the MS mortality 1952-1992. In summary, data on MS prevalence in Varmland and mortality both in Varmland and all Sweden from the past 100 years suggest an association with wood-related industries in 1913 and in the 1950s, whereas no consistent association was found for other industries. PMID- 21982619 TI - Metabolism and the heart: an overview of muscle, fat, and bone metabolism in heart failure. AB - PURPOSE OF REVIEW: To review original research studies and reviews that present data on changes of body compartments and its mutual cross-talk with respect to the failing heart predominantly in non-cachectic patients with chronic heart failure (HF). RECENT FINDINGS: Thanks to the integrative approach considering the whole organism, several recent studies suggested a complex network of communication between body compartments in respect to failing heart during the natural course of body wasting in non-cachectic patients with HF. Interestingly, recent studies suggest that failing heart trough secretion of natriuretic peptides acts on fat metabolism by inducing adiponectin secretion and lipolytic actions. Soluble myostatin released from the failing heart may induce skeletal muscle wasting in HF through an endocrine-like mechanism, as well. The likelihood that adipocyte-derived hormones influence bone status has been recently proven. Increased serum adiponectin was independently associated with reduced bone mass in elderly patients with non-cachectic HF. SUMMARY: The concept of body compartments cross-talk in respect to failing heart provides a very interesting paradigm of integrative physiology. Better understanding of body compartments changes and its complex biochemical interplay may provide more efficacious and forehand treatment to prevent and/or postpone disability and improve quality of life in patients with chronic HF. PMID- 21982620 TI - Takotsubo cardiomyopathy in a patient with coronary artery--left ventricular fistulae. PMID- 21982621 TI - Eating regulation and bulimic symptoms: the differential correlates of health focused and appearance-focused eating regulation. AB - Based on Self-Determination Theory, this study aimed to gain further insight in the pathway from eating regulation to bulimic symptoms by (a) examining diet specific need frustration as an intervening mechanism, (b) investigating the associations between different types of goals underlying eating regulation and diet-specific need frustration and bulimic symptoms, and (c) considering body dissatisfaction as an antecedent of eating regulation and eating regulation goals. In a sample of 244 female adolescents, SEM analyses showed that (a) the association between eating regulation and bulimic symptoms can be accounted for by need frustration, (b) appearance-focused and health-focused eating regulation are associated differentially with need frustration and bulimic symptoms, and (c) body dissatisfaction is related positively to eating regulation and appearance focused eating regulation. These findings suggest that the goals underlying one's eating regulation and the concept of need frustration help to understand when and why eating regulation is associated with bulimic symptoms. PMID- 21982622 TI - A randomised controlled pilot study comparing Mepitel((r)) and SurfaSoft((r)) on paediatric donor sites treated with Recell((r)). AB - This randomized controlled pilot study examined the effects of a silicone net dressing (Mepitel((r))) and a monofilament polyamide woven dressing (SurfaSoft((r))) on the rate of epithelialisation and epidermal maturation, pain, and ease of dressing removal on paediatric donor sites treated with epithelial cell suspension (ReCell((r))). Fifteen children (1-15 years) admitted for acute or reconstructive burns procedures in a tertiary referral hospital in Australia were randomly assigned to the experimental group, Mepitel((r)) (n=8) and to the control group, SurfaSoft((r)) (n=7). All donor sites were treated with ReCell((r)) and covered with the assigned dressing. Measurements of rate of epithelialisation and epidermal maturation, pain, and ease of dressing removal were recorded every two days until the wound was healed. Results showed that there was no difference in the rate of epidermal maturation between the two groups. Less pain and force to remove the dressing was shown in the Mepitel((r)) group when compared to SurfaSoft((r)). The rate of epithelialisation was found to be an unreliable measure. Although additional research is required to support the results of this study, these results suggest that Mepitel's((r)) pliable, self adhesive and atraumatic properties may improve healing of ReCell((r)) treated donor sites with less pain at dressing changes. This pilot study provides a strong base for further research in this area. PMID- 21982623 TI - Traumatic pneumothorax with air mimicking lung markings. PMID- 21982624 TI - Agreement between emergency medical services and expert blood pressure measurements. AB - BACKGROUND: Emergency Medical Services (EMS)-measured blood pressures (BPs) are utilized for administering medications in the field and for triage decisions. Retrospective work has demonstrated poor agreement between EMS and Emergency Department (ED) BP but has lacked a valid, reliable reference standard. STUDY OBJECTIVES: To compare EMS BP measurements with those of trained research assistants (RA) and observe measurement technique for sources of error. METHODS: A prospective study was performed with a large urban EMS. BP measurements were made by RA within 5 min of patients presenting to the ED. EMS personnel were asked about technique. EMS personnel were then observed while RA simultaneously measured BP. Analysis was performed using methods outlined by Bland and Altman. RESULTS: There were 100 patients enrolled for each phase. In the first phase, the mean difference in systolic BP was -3.8 +/- 18.6 mm Hg (95% confidence interval [CI] -8.3 to 0.59), and the mean difference in diastolic BP was 0.42 +/- 13.8 mm Hg (95% CI -3.3 to 4.1). In the second phase, the mean difference in systolic BP was -4.6 +/- 10.1 mm Hg (95% CI -6.6 to -2.6) and the mean difference in diastolic BP was -3.6 +/- 10.6 mm Hg (95% CI -3.6 to -0.2). EMS personnel failed to properly place the cuff or deflate it 2-3 mm Hg/s in over 90% of the readings. They failed to properly inflate the cuff in 74% of the patients, and failed to properly place the stethoscope in 40%. EMS personnel demonstrated a significant preference for the terminal digit of "0" (p < 0.0001). CONCLUSIONS: EMS and expert BP measurements showed smaller discrepancies than those previously noted, especially with simultaneous measurements. However, EMS demonstrated poor adherence to American Heart Association recommendations for measuring BP. EMS also showed terminal digit preference. PMID- 21982625 TI - Drowning terminology. PMID- 21982626 TI - Charles McBurney: McBurney's point. AB - Charles McBurney published a treatise on appendicitis in 1891, in which he described the exact point on the abdomen at which tenderness was maximal in cases of acute appendicitis--the point now known as "McBurney's point." He also described his approach to both the diagnosis and management of appendicitis, which at the time consisted of careful observation, total disuse of the stomach, and early laparotomy. Since 1891, many advances in the diagnosis of acute appendicitis have been made. Emergency physicians evaluating patients with abdominal pain may rely on laboratory studies, particularly the white blood cell count, and abdominal imaging with either ultrasound or computed tomography in addition to the history and physical examination. Despite these advances, tenderness to palpation over McBurney's point remains a key finding on abdominal examination in the assessment of patients with abdominal pain. PMID- 21982627 TI - Skin ultrastructural findings in type 2 Gaucher disease: diagnostic implications. AB - BACKGROUND: Type 2 Gaucher disease is a rare and progressive subtype of this lysosomal storage disorder, marked by rapid, early-onset neurodegeneration. Distinguishing type 2 from types 1 and 3 Gaucher disease has remained challenging, due to the lack of a clear correlation between phenotype and enzymatic activity or genotype. beta-glucocerebrosidase, the enzyme deficient in Gaucher disease, also has an essential role in maintaining epidermal permeability function, by regulating the ratio of ceramides to glucosylceramides in the stratum corneum of the skin. OBJECTIVES: To further assess the diagnostic utility of epidermal evaluations in distinguishing patients with type 2 Gaucher disease in an expanded cohort. STUDY DESIGN: Epidermal samples were evaluated from twenty children with type 2, three patients with type 3 Gaucher disease and two adults with type 1 Gaucher disease with different clinical manifestations and genotypes. Electron microscopy on ruthenium tetroxide post-fixed tissue was performed. RESULTS: Compared to controls and subjects with type 1 and type 3 Gaucher disease, only patients with type 2 Gaucher disease displayed characteristic electron dense, non-lamellar clefts and immature-lamellar membranes. CONCLUSION: The appearance of characteristic alterations in epidermal ultrastructure provides an early and specific diagnostic tool to help in distinguishing type 2 from the other types of Gaucher disease. PMID- 21982628 TI - Diurnal variations in blood phenylalanine of PKU infants under different feeding regimes. AB - In phenylketonuria (PKU) patients, diurnal fluctuations of blood phenylalanine (Phe) are different from healthy individuals. Until now this pattern has been studied in PKU patients over one year of age. OBJECTIVE: The aim of this observational study was to investigate diurnal patterns in PKU infants under one year of age receiving both the natural protein and Phe-free formula at the same time or in an alternating feeding scheme. METHODS: In 7 PKU infants (aged 3-8 months), diurnal variations in blood Phe concentrations were recorded: on day A they received natural protein and Phe-free formula combined in each feeding; on day B they received these in an alternating feeding scheme. The number of feedings, total protein, and energy intake was similar on both study days. Blood samples were taken before each feeding. RESULTS: The means (+/- SD) of the difference between the individual minimum and maximum blood Phe concentrations were 81(+/- 50) MUmol/L and 104(+/- 26) MUmol/L on days A and B, respectively (n.s.). Fifty and 30% of the samples were below target range for age (120 MUmol/L), while only 3% and 6% were above target range (360 MUmol/L) on days A and B respectively (n.s.). CONCLUSION: Both feeding regimes, i.e. the natural protein and Phe-free formula combined in each feeding or alternating, resulted in comparable diurnal fluctuations of blood Phe concentrations. PMID- 21982629 TI - Endoplasmic reticulum stress induces autophagy through activation of p38 MAPK in fibroblasts from Pompe disease patients carrying c.546G>T mutation. AB - Pompe disease (glycogen storage disease type II) is an autosomal recessive myopathic disorder arising from the deficiency of lysosomal acid alpha glucosidase (GAA). Activation of autophagy is a key pathophysiological feature in skeletal muscle fibers and fibroblasts from patients with Pompe disease. The accumulation of autophagic vacuoles has been shown to interfere with the efficacy of enzyme replacement therapy with recombinant human GAA. However, the induction mechanism of autophagy in Pompe disease is still unclear. In this study, we show that misfolded GAA-induced endoplasmic reticulum (ER) stress triggers autophagy in a manner regulated by p38 MAPK signaling pathways in fibroblasts from late onset patients with Pompe disease. By studying normal fibroblasts and patient fibroblasts carrying a c.546G>T mutation, we uncovered that mutant GAA was rapidly degraded by proteasome. In addition, we found both activation of ER stress response and autophagy in these patient fibroblasts. Treatment with N butyl-deoxynojirimycin (NB-DNJ), which acts as a pharmacological chaperone for certain mutant forms of GAA, led to attenuation of not only ER stress, but also autophagy in patient fibroblasts. Levels of phosphorylated p38 MAPK observed in patient fibroblasts were decreased after treatment with NB-DNJ. The autophagic response in patient fibroblasts was also negatively regulated by treatment with the p38 MAPK inhibitor SB203580. These findings define a critical role for ER stress in the activation of autophagy due to GAA mutation, and provide evidence that chaperone therapy may be a useful treatment for alleviation of autophagy in Pompe disease patients carrying a chaperon-responsive mutation. PMID- 21982630 TI - Immigration and the health of U.S. black adults: does country of origin matter? AB - Previous work suggests that regional variation in pre-migration exposure to racism and discrimination, measured by a region's racial composition, predicts differences in individual-level health among black immigrants to the United States. We exploit data on both region and country of birth for black immigrants in the United States and methodology that allows for the identification of arrival cohorts to test whether there are sending country differences in the health of black adults in the United States that support this proposition. While testing this hypothesis, we also document heterogeneity in health across arrival cohorts and by duration of U.S. residence among black immigrants. Using data on working-age immigrant and U.S.-born blacks taken from the 1996-2010 waves of the March Current Population Survey, we show that relative to U.S.-born black adults, black immigrants report significantly lower odds of fair/poor health. After controlling for relevant social and demographic characteristics, immigrants' cohort of arrival, and immigrants' duration in the United States, our models show only modest differences in health between African immigrants and black immigrants who migrate from the other major sending countries or regions. Results also show that African immigrants maintain their health advantage over U.S.-born black adults after more than 20 years in the United States. In contrast, black immigrants from the Caribbean who have been in the United States for more than 20 years appear to experience some downward health assimilation. In conclusion, after accounting for relevant factors, we find that there are only modest differences in black immigrant health across countries of origin. Black immigrants appear to be very highly selected in terms of good health, although there are some indications of negative health assimilation for black immigrants from the Caribbean. PMID- 21982631 TI - Income inequality, social capital and self-rated health and dental status in older Japanese. AB - The erosion of social capital in more unequal societies is one mechanism for the association between income inequality and health. However, there are relatively few multi-level studies on the relation between income inequality, social capital and health outcomes. Existing studies have not used different types of health outcomes, such as dental status, a life-course measure of dental disease reflecting physical function in older adults, and self-rated health, which reflects current health status. The objective of this study was to assess whether individual and community social capital attenuated the associations between income inequality and two disparate health outcomes, self-rated health and dental status in Japan. Self-administered questionnaires were mailed to subjects in an ongoing Japanese prospective cohort study, the Aichi Gerontological Evaluation Study Project in 2003. Responses in Aichi, Japan, obtained from 5715 subjects and 3451 were included in the final analysis. The Gini coefficient was used as a measure of income inequality. Trust and volunteering were used as cognitive and structural individual-level social capital measures. Rates of subjects reporting mistrust and non-volunteering in each local district were used as cognitive and structural community-level social capital variables respectively. The covariates were sex, age, marital status, education, individual- and community-level equivalent income and smoking status. Dichotomized responses of self-rated health and number of remaining teeth were used as outcomes in multi-level logistic regression models. Income inequality was significantly associated with poor dental status and marginally significantly associated with poor self-rated health. Community-level structural social capital attenuated the covariate adjusted odds ratio of income inequality for self-rated health by 16% whereas the association between income inequality and dental status was not substantially changed by any social capital variables. Social capital partially accounted for the association between income inequality and self-rated health but did not affect the strong association of income inequality and dental status. PMID- 21982632 TI - Time-bound opportunity costs of informal care: consequences for access to professional care, caregiver support, and labour supply estimates. AB - The opportunity costs associated with the provision of informal care are usually estimated based on the reduced potential of the caregiver to partake in paid work (both in terms of whether they are able to undertake paid work, and if so the hours of work undertaken). In addition to the hours of informal care provided, these opportunity costs are also likely determined by the necessity to perform particular informal care tasks at specific moments of the day. The literature, to date, has largely overlooked this dimension of informal care. We used Dutch data from time use diaries which report patterns of informal care throughout the day which enables investigation of when particular activities are undertaken. We found that whereas some tasks must be performed at a relatively fixed time of day, others are shiftable and can be performed at other times or even on different days. Household and organisation activities are more likely to be undertaken by employed caregivers, and seem largely to be shiftable; whereas personal care contains unshiftable activities. This implies additional opportunity costs of providing personal care tasks - we term these "time-bound" opportunity costs. Since the care recipient's need for care may in part relate to unshiftable tasks, we conclude that one should be careful with using care need as an instrument of informal care in labour supply equations. PMID- 21982633 TI - Intersectionality and gender mainstreaming in international health: using a feminist participatory action research process to analyse voices and debates from the global south and north. AB - Critiques of gender mainstreaming (GM) as the officially agreed strategy to promote gender equity in health internationally have reached a critical mass. There has been a notable lack of dialogue between gender advocates in the global north and south, from policy and practice, governments and non-governmental organisations (NGOs). This paper contributes to the debate on the shape of future action for gender equity in health, by uniquely bringing together the voices of disparate actors, first heard in a series of four seminars held during 2008 and 2009, involving almost 200 participants from 15 different country contexts. The series used (Feminist) Participatory Action Research (FPAR) methodology to create a productive dialogue on the developing theory around GM and the at times disconnected empirical experience of policy and practice. We analyse the debates and experiences shared at the seminar series using concrete, context specific examples from research, advocacy, policy and programme development perspectives, as presented by participants from southern and northern settings, including Kenya, Mozambique, India, the Democratic Republic of Congo, Canada and Australia. Focussing on key discussions around sexualities and (dis)ability and their interactions with gender, we explore issues around intersectionality across the five key themes for research and action identified by participants: (1) Addressing the disconnect between gender mainstreaming praxis and contemporary feminist theory; (2) Developing appropriate analysis methodologies; (3) Developing a coherent theory of change; (4) Seeking resolution to the dilemmas and uncertainties around the 'place' of men and boys in GM as a feminist project; and (5) Developing a politics of intersectionality. We conclude that there needs to be a coherent and inclusive strategic direction to improve policy and practice for promoting gender equity in health which requires the full and equal participation of practitioners and policy makers working alongside their academic partners. PMID- 21982634 TI - Childhood- and later-onset vitiligo have diverse epidemiologic and clinical characteristics. AB - BACKGROUND: Vitiligo onset during childhood is common. There are limited data regarding childhood-onset vitiligo. OBJECTIVE: We sought to provide an epidemiologic and clinical comparison between childhood- and later-onset vitiligo. METHODS: Two groups of patients were included in this cross-sectional study. Consecutive patients examined at the Vitiligo Clinic of Andreas Sygros Hospital for Skin and Venereal Diseases, Athens, Greece, from January 2005 to December 2009 with a disease onset before the age of 12 years were included in the childhood-onset group. The later-onset group included randomly selected patients who were examined at the same period and had a disease onset after the age of 12 years. After clinical examination, a standardized questionnaire was completed for each patient. RESULTS: In all, 126 patients were included in the childhood-onset and 107 patients in the later-onset group. Childhood-onset vitiligo: (1) involved different sites at initial presentation, (2) included more cases of segmental type, and (3) was characterized by a higher prevalence of allergic diseases and a lower prevalence of thyroid diseases. Longer duration of disease and a positive family history of thyroid disease were associated with the presence of thyroid disease only in the childhood-onset group. In the later-onset group, only female sex was associated with the presence of thyroid disease. LIMITATIONS: The study was conducted in a hospital specializing in skin diseases and a selection bias toward more severe vitiligo cases is possible. CONCLUSIONS: Childhood-onset vitiligo had distinct epidemiologic and clinical characteristics, compared with later-onset disease. PMID- 21982635 TI - Saurian papulosis: a new clinicopathological entity. AB - BACKGROUND: Epidermal keratinization disorders comprise a heterogeneous group of skin diseases that share the common feature of abnormal epidermal maturation, often leading to a disturbed stratum corneum. OBJECTIVE: To describe two cases of an unusual disorder of epidermal keratinization. METHODS: The clinical features of two unrelated patients with a long-standing widespread cutaneous eruption are described. Histopathologic examination and immunohistochemical studies were performed on skin biopsy specimens. RESULTS: The eruption was characterized by symmetric erythematous, flat, discrete papules with a polygonal shape and fine scaling. The papules covered most of the skin surface and, in some areas of the trunk, they were arranged along the lines of cleavage, parallel to the ribs. There was no facial, mucosal, nail, or palmoplantar involvement; the teeth and hair were normal. The first patient had a sister with an identical eruption, and a brother of the second patient was said to have similar skin lesions. Histopathology revealed well-demarcated areas of compact eosinophilic orthokeratotic hyperkeratosis overlying a slightly acanthotic epidermis. Lesional skin showed weaker immunoexpression for connexin 43 compared with normal skin. LIMITATIONS: Only two patients and one sibling were investigated. CONCLUSION: We propose the name "saurian papulosis" to describe this newly described clinicopathologic entity. PMID- 21982636 TI - Accuracy in melanoma detection: a 10-year multicenter survey. AB - BACKGROUND: Early excision is the only strategy to reduce melanoma mortality, but unnecessary excision of benign lesions increases morbidity and healthcare costs. OBJECTIVE: To assess accuracy in melanoma detection based on number-needed-to excise (NNE) values over a 10-year period. METHODS: Information was retrieved on all histopathologically confirmed cutaneous melanomas or melanocytic nevi that were excised between 1998 and 2007 at participating clinics. NNE values were calculated by dividing the total number of excised lesions by the number of melanomas. Analyses included changes in NNE over time, differences in NNE between specialized clinical settings (SCS) versus non-specialized clinical settings (NSCS), and patient factors influencing NNE. RESULTS: The participating clinics contributed a total of 300,215 cases, including 17,172 melanomas and 283,043 melanocytic nevi. The overall NNE values achieved in SCS and NSCS in the 10-year period were 8.7 and 29.4, respectively. The NNE improved over time in SCS (from 12.8 to 6.8), but appeared unchanged in NSCS. Most of the effect on NNE in SCS was due to a greater number of excised melanomas. Higher NNE values were observed in patients younger than 40 years and for lesions located on the trunk. LIMITATIONS: No data concerning the use of dermatoscopy and digital monitoring procedures were collected from the participating centers. CONCLUSION: Over the 10 year study period, accuracy in melanoma detection improved only in specialized clinics maybe because of a larger use of new diagnostic techniques such as dermatoscopy. PMID- 21982637 TI - Role of histone deacetylase expression in intrahepatic cholangiocarcinoma. AB - INTRODUCTION: Histone deacetylase (HDAC) plays an important role in chromatin remodeling and gene expression, and in regulating cell cycle progression and differentiation. Furthermore, hypoxic conditions in the malignant tumor enhance HDAC function and increased HDAC activity is closely involved in worse malignant behavior through hypoxia inducible factor (HIF) activation. The aim of this study was to elucidate the correlation between HDAC expression and tumor malignant behavior including HIF-1alpha expression in intrahepatic cholangiocarcinoma (IHCC). METHODS: Thirty-five patients with IHCC who underwent hepatic resection were evaluated. HDAC1 and HIF-1alpha expressions were determined immunohistochemically, and the patients were divided into 2 groups: the HDAC1 positive group (n = 21) and the HDAC1 negative group (n = 14). Clinicopathologic variables including HIF-1alpha expression were compared between the 2 groups. RESULTS: HDAC1 expression correlated significantly with higher stage carcinoma, lymph node metastasis, and vascular invasion. The prognosis in the HDAC1 positive group was poorer than in the HDAC1 negative group (5-year survival: 78% vs 8%, P = .001). Furthermore, disease free survival rate in the HDAC1 positive group had significantly worse than that in the HDAC1 negative group (P = .0003). In the multivariate analysis, HDAC1 positive expression was identified as the only independent prognostic factor for disease free survival (Hazard Ratio: 7.194, P = .0018). Furthermore, there was a significant correlation between HDAC1 expression and HIF-1alpha expression (P = .007). CONCLUSION: These findings suggested that HDAC1 positive expression was a potential new prognostic indicator of IHCC, and a possible promising molecular target through the regulation of HIF-1alpha. PMID- 21982638 TI - Unrelated cord blood transplantation after myeloablative conditioning regimen in adolescent and young adult patients with hematologic malignancies: a single institute analysis. AB - We report the results of unrelated cord blood transplantation (CBT) after myeloablative conditioning regimen in 16 patients with hematologic malignancies from 15 to 20 years old. The median times of myeloid and platelet engraftment were 21 and 38 days, respectively. The cumulative incidences of acute graft-vs host disease (GVHD) was 62.0%, all of which were grade I or II, and that of extensive-type chronic GVHD was 12.5%. The probabilities of overall and disease free survival at 3 years were 68.2% and 48.6%, respectively, comparable to adult or childhood cases. Adolescents and young adult patients with hematologic malignancies who have no HLA-matched adult donors could be considered as candidates for CBT. PMID- 21982639 TI - Bloom's and myelodysplastic syndromes: Report of a rare pediatric case with gain of an isochromosome 5p. PMID- 21982640 TI - Analysis of chromosome 12p deletion in plasma cell dyscrasias. AB - The prognostic relevance of 12p deletion is controversial in multiple myeloma (MM) and the status of 12p deletion is unknown in other plasma cell disorders. We investigated 12p deletion in 88 patients with MM, 19 patients with monoclonal gammopathy of undetermined significance (MGUS), and 17 patients with plasma cell leukemia (PCL). Cytoplasmic immunoglobulin light chain immunofluorescence with simultaneous FISH analysis (cIg-FISH) detected hemizygous 12p deletion in 8% of MM and 24% of PCL, respectively, but in none of the MGUS cases (p=0.0366). 12p deletions were found in 5 of 7 (71%) MM patients at diagnosis with stage III disease (Durie-Salmon), 2 of 7 (28%) with stage I or II. Of 11 cases with 12p deletions, 6 (55%) had coexistence of p53 deletions, including 3 of 7 (42%) MM, and 3 of 4 (75%) PCL cases. There were no significant differences in progression free or overall survivals in MM patients with or without 12p deletions. Our results do not support the use of 12p deletion as a prognostic marker in MM, rather, it tends to occur in advanced disease, may represent a secondary change associated with the disease progression. PMID- 21982641 TI - Implementation of flow cytometry in the diagnostic work-up of myelodysplastic syndromes in a multicenter approach: report from the Dutch Working Party on Flow Cytometry in MDS. AB - Flow cytometry (FC) is recognized as an important tool in the diagnosis of myelodysplastic syndromes (MDS) especially when standard criteria fail. A working group within the Dutch Society of Cytometry aimed to implement FC in the diagnostic work-up of MDS. Hereto, guidelines for data acquisition, analysis and interpretation were formulated. Based on discussions on analyses of list mode data files and fresh MDS bone marrow samples and recent literature, the guidelines were modified. Over the years (2005-2011), the concordance between the participating centers increased indicating that the proposed guidelines contributed to a more objective, standardized FC analysis, thereby ratifying the implementation of FC in MDS. PMID- 21982642 TI - Au-nanoclusters incorporated 3-amino-5-mercapto-1,2,4-triazole film modified electrode for the simultaneous determination of ascorbic acid, dopamine, uric acid and nitrite. AB - A novel biosensor has been constructed by the electrodeposition of Au nanoclusters (nano-Au) on poly(3-amino-5-mercapto-1,2,4-triazole) (p-TA) film modified glassy carbon electrode (GCE) and employed for the simultaneous determination of dopamine (DA), ascorbic acid (AA), uric acid (UA) and nitrite (NO(2)(-)). NH(2) and SH groups exposed to the p-TA layer are helpful for the electrodeposition of nano-Au. The combination of nano-Au and p-TA endow the biosensor with large surface area, good biological compatibility, electricity and stability, high selectivity and sensitivity and flexible and controllable electrodeposition process. In the fourfold co-existence system, the linear calibration plots for AA, DA, UA and NO(2)(-) were obtained over the range of 2.1 50.1 MUM, 0.6-340.0 MUM, 1.6-110.0 MUM and 15.9-277.0 MUM with detection limits of 1.1*10(-6) M, 5.0*10(-8) M, 8.0*10(-8) M and 8.9*10(-7) M, respectively. In addition, the modified biosensor was applied to the determination of AA, DA, UA and NO(2)(-) in urine and serum samples by using standard adding method with satisfactory results. PMID- 21982643 TI - Handheld device for real-time, quantitative, LAMP-based detection of Salmonella enterica using assimilating probes. AB - A simple handheld instrument was designed to enable real-time detection of the LAMP reaction in a standard PCR tube using newly described assimilating probes as sequence-specific reporter molecules. The system was validated using DNA isolated from Salmonella enterica, demonstrating accurate temperature control with little power and little overshoot of setpoint temperatures, with rapid and accurate detection often in less than 30 min and within 20 min for reactions with high (>10(5)) genome copy numbers. The system could be used for quantitative determination of pathogen DNA, with a limit of detection of about 15 genome copies in purified DNA or 25 cells in DNA extracts from chicken rinsate- comparable to values obtained when running the same reaction on a commercial benchtop real-time PCR instrument. Positive classification of standards nominally containing a single genome equivalent was demonstrated, and no false positives were reported. Detection of S. enterica in rinsate from a contaminated chicken sample required 48 h enrichment prior to the LAMP reaction or plating on semi selective media. The new system demonstrates a major compelling advantage of the LAMP reaction, in that it may be enabled in simple, low-power, handheld devices without sophisticated custom miniaturized disposables. This new diagnostic system is especially promising for on-site diagnostics in the food and agricultural industries where laboratory space is often primitive if it is available at all. PMID- 21982644 TI - Invited commentary. PMID- 21982645 TI - A syndecan-4 hair trigger initiates wound healing through caveolin- and RhoG regulated integrin endocytosis. AB - Cell migration during wound healing requires adhesion receptor turnover to enable the formation and disassembly of cell-extracellular matrix contacts. Although recent advances have improved our understanding of integrin trafficking pathways, it is not known how extracellular ligand engagement controls receptor dynamics. Using atomic force microscopy, we have measured cell avidity for fibronectin and defined a mechanism for the outside-in regulation of alpha(5)beta(1)-integrin. Surprisingly, adhesive strength was attenuated by the syndecan-4-binding domain of fibronectin due to a rapid triggering of alpha(5)beta(1)-integrin endocytosis. Association of syndecan-4 with PKCalpha was found to trigger RhoG activation and subsequent dynamin- and caveolin-dependent integrin uptake. Like disruption of syndecan-4 or caveolin, gene disruption of RhoG in mice was found to retard closure of dermal wounds due to a migration defect of the fibroblasts and keratinocytes of RhoG null mice. Thus, this syndecan-4-regulated integrin endocytic pathway appears to play a key role in tissue repair. PMID- 21982647 TI - Efficacy of exercise-based cardiac rehabilitation post-myocardial infarction: a systematic review and meta-analysis of randomized controlled trials. AB - BACKGROUND: Exercise-based cardiac rehabilitation (CR) remains an underused tool for secondary prevention post-myocardial infarction (MI). In part, this arises from uncertainty regarding the efficacy of CR, particularly with respect to reinfarction, where previous studies have failed to show consistent benefit. We therefore undertook a meta-analysis of randomized controlled trials (RCTs) to (1) estimate the effect of CR on cardiovascular outcomes and (2) examine the effect of CR program characteristics on the magnitude of CR benefits. METHODS: We systematically searched MEDLINE as well as relevant bibliographies to identify all English-language RCTs examining the effects of exercise-based CR among post MI patients. Data were aggregated using random-effects models. Stratified analyses were conducted to examine the impact of RCT-level characteristics on treatment benefits. RESULTS: We identified 34 RCTs (N = 6,111). Overall, patients randomized to exercise-based CR had a lower risk of reinfarction (odds ratio [OR] 0.53, 95% CI 0.38-0.76), cardiac mortality (OR 0.64, 95% CI 0.46-0.88), and all cause mortality (OR 0.74, 95% CI 0.58-0.95). In stratified analyses, treatment effects were consistent regardless of study periods, duration of CR, or time beyond the active intervention. Exercise-based CR had favorable effects on cardiovascular risk factors, including smoking, blood pressure, body weight, and lipid profile. CONCLUSIONS: Exercise-based CR is associated with reductions in mortality and reinfarction post-MI. Our secondary analyses suggest that even shorter CR programs may translate into improved long-term outcomes, although these results need to be confirmed in an RCT. PMID- 21982646 TI - A conserved Pbx-Wnt-p63-Irf6 regulatory module controls face morphogenesis by promoting epithelial apoptosis. AB - Morphogenesis of mammalian facial processes requires coordination of cellular proliferation, migration, and apoptosis to develop intricate features. Cleft lip and/or palate (CL/P), the most frequent human craniofacial birth defect, can be caused by perturbation of any of these programs. Mutations of WNT, P63, and IRF6 yield CL/P in humans and mice; however, how these genes are regulated remains elusive. We generated mouse lines lacking Pbx genes in cephalic ectoderm and demonstrated that they exhibit fully penetrant CL/P and perturbed Wnt signaling. We also characterized a midfacial regulatory element that Pbx proteins bind to control the expression of Wnt9b-Wnt3, which in turn regulates p63. Altogether, we establish a Pbx-dependent Wnt-p63-Irf6 regulatory module in midfacial ectoderm that is conserved within mammals. Dysregulation of this network leads to localized suppression of midfacial apoptosis and CL/P. Ectopic Wnt ectodermal expression in Pbx mutants rescues the clefting, opening avenues for tissue repair. PMID- 21982648 TI - Measuring and targeting aldosterone and renin in atherosclerosis-a review of clinical data. AB - Our understanding of the development and progression of atherosclerosis has increased substantially over the past decades. A significant role for the renin angiotensin-aldosterone system (RAAS) in this process has gained appreciation in recent years. Preclinical and clinical studies have associated components of the RAAS with various cardiovascular disease conditions. Classically known for its contribution to hypertension, dysregulation of the system is now also believed to promote vascular inflammation, fibrosis, remodeling, and endothelial dysfunction, all intimately related to atherosclerosis. The reduction in cardiovascular mortality and morbidity, as seen with the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, supports the concept that RAAS is involved in the pathogenesis of atherosclerotic disease. However, the underlying molecular mechanisms of the pathophysiology remain to be completely understood. Evidence points toward additional benefit from therapeutic approaches aiming at more complete inhibition of the system and the possible utility of renin or aldosterone in the prediction of cardiovascular outcome. This review will summarize the current knowledge from clinical studies regarding the presumptive role of renin and aldosterone in the prediction and management of patients with atherosclerosis. For this purpose, a literature search was performed, focusing on available clinical data regarding renin or aldosterone and cardiovascular outcome. PMID- 21982649 TI - Interleukin-1beta inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). AB - BACKGROUND: Inflammation contributes to all phases of the atherothrombotic process, and patients with elevated inflammatory biomarkers such as high sensitivity C-reactive protein (hsCRP) have increased vascular risk. Yet, it remains unknown whether direct inhibition of inflammation will reduce cardiovascular event rates. DESIGN: The CANTOS will evaluate whether interleukin 1beta (IL-1beta) inhibition as compared with placebo can reduce rates of recurrent myocardial infarction, stroke, and cardiovascular death among stable patients with coronary artery disease who remain at high vascular risk due to persistent elevations of hsCRP (>2 mg/L) despite contemporary secondary prevention strategies. Canakinumab is a human monoclonal antibody that selectively neutralizes IL-1beta, a proinflammatory cytokine that plays multiple roles in the atherothrombotic process and that undergoes activation by the nucleotide-binding leucine-rich repeat-containing pyrin receptor 3 inflammasome, a process promoted by cholesterol crystals. Canakinumab significantly reduces systemic C-reactive protein and other inflammatory biomarker levels, is generally well tolerated, and is currently indicated for the treatment of inherited IL 1beta driven inflammatory diseases such as the Muckle-Wells syndrome. In a multinational collaborative effort using an event-driven intention-to-treat protocol, CANTOS will randomly allocate 17,200 stable postmyocardial infarction patients with persistent elevation of hsCRP to either placebo or to canakinumab at doses of 50, 150, or 300 mg every 3 months, administered subcutaneously. All participants will be followed up over an estimated period of up to 4 years for the trial primary end point (nonfatal myocardial infarction, nonfatal stroke, cardiovascular death) as well as for other vascular events, total mortality, adverse events, and specific clinical end points associated with inflammation including new onset diabetes, venous thrombosis, and atrial fibrillation. SUMMARY: If positive, CANTOS would confirm the inflammatory hypothesis of atherothrombosis and provide a novel cytokine-based therapy for the secondary prevention of cardiovascular disease and new-onset diabetes. PMID- 21982650 TI - Outcomes registry for better informed treatment of atrial fibrillation: rationale and design of ORBIT-AF. AB - BACKGROUND: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with an increased risk of stroke, heart failure, and death. Data on contemporary treatment patterns and outcomes associated with AF in clinical practice are limited. METHODS/DESIGN: The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation is a multicenter, prospective, ambulatory-based registry of incident and prevalent AF. The registry will be a nationwide collaboration of health care providers, including internists, primary care physicians, cardiologists, and electrophysiologists. Initial target enrollment is approximately 10,000 patients to be recruited from approximately 200 US outpatient practices. Enrolled patients will be observed for >=2 years. A patient-reported outcomes substudy in >=1,500 patients will provide serial quality-of-life assessments. The goal is to characterize treatment and outcomes of patients with AF, thereby promoting better quality of AF care and improved patient outcomes. CONCLUSION: The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation will provide insights into "real-world" treatment including rate and rhythm control, stroke prevention, transitions to new therapies, and clinical and patient-centered outcomes among patients with AF in community practice settings (ClinicalTrials.gov NCT01165710). PMID- 21982651 TI - Study design and rationale for the Stabilization of pLaques usIng Darapladib Thrombolysis in Myocardial Infarction (SOLID-TIMI 52) trial in patients after an acute coronary syndrome. AB - BACKGROUND: Higher levels of lipoprotein-associated phospholipase A(2) (Lp PLA(2)) are associated with a higher risk of cardiovascular events and may play a causal role in atherogenesis. Darapladib inhibits Lp-PLA(2) activity in plasma and in arterial plaques and may confer clinical benefit in preventing cardiovascular events. STUDY DESIGN: The SOLID-TIMI 52 trial is a randomized, double-blind, placebo-controlled, multicenter, event-driven trial. Approximately 13,000 subjects are being randomized to darapladib (160 mg enteric-coated tablet daily) or matching placebo within 30 days of hospitalization with an acute coronary syndrome. The primary end point is the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Secondary end points include major and total coronary events, individual components of the primary end point, and all-cause mortality. The study will continue until approximately 1,500 primary end point events have occurred to achieve 90% power to detect a 15.5% reduction in the primary end point. The median treatment duration is anticipated to be approximately 3 years, with a total study duration of approximately 4.1 years. CONCLUSIONS: The SOLID-TIMI 52 trial will determine the clinical benefit of direct inhibition of Lp-PLA(2) activity with darapladib in patients after an acute coronary syndrome. PMID- 21982652 TI - EXamination of cArdiovascular outcoMes with alogliptIN versus standard of carE in patients with type 2 diabetes mellitus and acute coronary syndrome (EXAMINE): a cardiovascular safety study of the dipeptidyl peptidase 4 inhibitor alogliptin in patients with type 2 diabetes with acute coronary syndrome. AB - Comprehensive safety evaluation of new drugs for diabetes mellitus is needed in the area of cardiovascular (CV) outcomes, particularly in populations with high CV risk. Alogliptin, a dipeptidyl peptidase 4 inhibitor, is under development for the treatment of type 2 diabetes mellitus alone or in combination with other antidiabetic therapies. Long-term CV safety of alogliptin is being established in a randomized, placebo-controlled clinical study in patients with acute coronary syndrome (ACS) using an analytical approach that has both an interim and final assessment. The primary CV end point for this trial is a composite of CV death, nonfatal myocardial infarction, and nonfatal stroke. Approximately 5,400 men and women with type 2 diabetes and ACS (acute myocardial infarction or unstable angina) are being recruited and will be followed up for up to 4.5 years postrandomization. The statistical plan for the trial uses a design that evaluates the hazard ratio (HR) of alogliptin to placebo first based on the primary CV composite end point after accrual of 80 to 150 primary CV events and again when there are 550 to 650 primary CV events. In the first series of analyses, the upper bound of a group-sequential 1-sided repeated CI for the HR must be <=1.8 for registration in the United States. At end of study, the upper bound of a subsequent group-sequential 1-sided repeated CI for the HR must be <=1.3. For both group sequential analyses, the repeated CIs are calculated to insure simultaneous coverage probabilities of 97.5% for the true HR. Study progress: More than 2,000 ACS patients were randomized as of June 2011. EXAMINE will define the CV safety profile of this dipeptidyl peptidase 4 inhibitor in patients at high risk for CV events. PMID- 21982653 TI - The National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC): results from phase I and scientific opportunities in phase II. AB - BACKGROUND: Genetically triggered thoracic aortic conditions (GenTACs) represent an important problem for patients and their families. Accordingly, the National Heart, Lung, and Blood Institute established the first phase of its national GenTAC Registry in 2006. ENROLLMENT AND DIAGNOSES: Between 2007 and 2010, 6 enrolling centers established the GenTAC I Registry consisting of 2,046 patients (Marfan syndrome 576 [28.2%], bicuspid aortic valve disease 504 [24.6%], aneurysm or dissection age <50 years 369 [18%], and others). Biologic samples for DNA analyses (white blood cells or saliva) are available in 97%, and stored plasma is available in 60% of enrollees. RESULTS: Initial scientific inquiry using the GenTAC Registry has included validation studies of genetic causes for aortic syndromes, potential usefulness of transforming growth factor beta (TGFB) blood levels in Marfan subjects, and current surgical approaches to ascending aortic conditions. FUTURE OPPORTUNITY: The second phase of GenTAC will allow biannual follow-up of GenTAC I enrollees for up to 9 years, enrollment of an additional 1,500 subjects, further integration of imaging findings with clinical and genetic data through utilization of an imaging core laboratory, important validation of phenotype-genotype correlations through a phenotyping core laboratory, and integration of a scientific advisory committee to help define the full range and depth of the Registry's scientific capabilities. The registry resources are available to the external scientific community through an application process accessible at https://gentac.rti.org. PMID- 21982654 TI - Prospective study of infective endocarditis from a developing country. AB - BACKGROUND: There has been a considerable change in the profile of infective endocarditis (IE) worldwide. However, prospective studies of IE from developing countries are rare. AIM: The aim of this study was to evaluate predisposing factors, clinical presentation, echocardiography, microbiology, in-hospital course, and outcomes of patients with definite IE. METHODS: This was a prospective observational study of consecutive cases of definite IE as per the modified Duke criteria. RESULTS: Between 2004 and 2006, a total of 104 cases of definite IE were identified. The mean age was 23.5 years (interquartile range, 9 38 years), with a male preponderance (2.5:1). Congenital heart disease accounted for 39.4% cases of IE, followed by native valve disease (29.8%), prosthetic valve disease (20%), and normal valves (7.7%). Echocardiography was diagnostic in 96.7% of the patients. Positive cultures were obtained in only 41% of the cases, with staphylococci and streptococci being the most common organisms. Seventy-three percent of the cases had at least 1 major complication. Only 15% of the cases underwent surgery for IE. The in-hospital mortality was 26%. On multivariate analysis, an underlying heart disease other than native valve disease and septic shock were independent predictors of mortality. CONCLUSION: The mean age of IE in India is significantly lower than that in the West. Unlike previous reports, congenital heart disease is the major predisposing factor. Culture positivity rates and surgery for IE are unacceptably low. In conclusion, IE in India is associated with a very high morbidity and mortality. PMID- 21982655 TI - Prognostic value of serial measurements of highly sensitive cardiac troponin I in stable outpatients with nonischemic chronic heart failure. AB - BACKGROUND: Cardiac troponin I (cTnI) is a useful biomarker in patients with chronic heart failure (CHF), and a highly sensitive cTnI (hs-cTnI) commercial assay has become available. However, the prognostic role of serial measurements of hs-cTnI in stable outpatients with CHF remains unknown. METHODS: At entry to the study, we evaluated 95 stable outpatients with nonischemic CHF showing a serum hs-cTnI (Centaur TnI-Ultra [Siemens Medical Solution Diagnostics, New York, NY], lower limit of detection 0.006 ng/mL) value >=0.006 ng/mL. To evaluate the role of repetitive measurements of hs-cTnI, we performed echocardiography and measured serum levels of cTnI and N-terminal proBNP at baseline and 6 months later and then prospectively followed up these patients for 4.25 years. RESULTS: During long-term follow-up, there were 27 cardiac deaths. On multivariate analyses, high plasma N-terminal pro-brain natriuretic peptide (>=711 pg/mL, P = .0008), high serum hs-cTnI at baseline (>=0.03 ng/mL, P = .0011), and an increase in hs-cTnI (Deltahs-cTnI >=0 ng/mL, P = .022) after 6 months were independent significant prognostic predictors. The hazard ratio for mortality of patients with high hs-cTnI (>=0.03 ng/mL) and an increase in hs-cTnI (Deltahs-cTnI >=0 ng/mL) was 3.59 (95% CI 1.3-9.9, P = .014) compared with that of those with high hs-cTnI (>=0.03 ng/mL) and a decrease in hs-cTnI (Deltahs-cTnI <0 ng/mL). CONCLUSIONS: These findings indicated that not only the serum concentration of hs cTnI at baseline but also an increase in hs-cTnI were independent and useful prognostic predictors in patients with nonischemic CHF. PMID- 21982656 TI - The impact of left ventricular size on response to cardiac resynchronization therapy. AB - Patients with nondilated (NDCM) or severely dilated cardiomyopathies (SDCM) have been underrepresented in clinical trials of cardiac resynchronization therapy (CRT). We examined changes in left ventricular ejection fraction (LVEF) and survival in patients with NDCM or SDCM compared with those with traditionally studied moderately dilated cardiomyopathy. METHODS: We evaluated 800 consecutive patients undergoing the original implantation of a biventricular pacemaker between January 2004 and August 2007. For inclusion, patients had a baseline and pre-CRT echocardiogram, an LVEF <=40%, a US social security number, and New York Heart Association class II to IV symptoms on standard medical therapy. Patients with a follow-up echocardiogram >2 months after device implantation were included in an analysis of remodeling. Using multivariate models, the impact of baseline left ventricular end-diastolic diameter (LVEDD) on change in LVEF and all-cause mortality was assessed. RESULTS: A total of 668 patients met inclusion criteria and were included in the assessment of mortality. Four hundred seventy-one had an appropriately timed follow-up echocardiogram and were included in the analysis of remodeling. Patients in all 3 groups realized improvements in LVEF (%) after CRT as follows: NDCM (n = 137; LVEDD <=5.5 cm) 10.0 +/- 12.7, P < .001; moderately dilated cardiomyopathy (n = 233; LVEDD 5.6-6.9 cm) 8.2 +/- 11.3, P < .001; and SDCM (n = 101; LVEDD >=7.0 cm) 5.4 +/- 9.4, P < .001. In multivariate analysis, baseline LVEDD was inversely associated with change in LVEF (parameter estimate 3.13 +/- 0.56, P < .001) and directly associated with increased all-cause mortality (hazard ratio 1.25 [1.05-1.47] P = .01). CONCLUSION: Patients with NDCM and SDCM experience significant improvements in LVEF after CRT. The degree of baseline left ventricular dilatation before CRT is an important predictor of subsequent changes in LVEF and survival. PMID- 21982657 TI - A double-blind, randomized, controlled, multicenter study to assess the safety and cardiovascular effects of skeletal myoblast implantation by catheter delivery in patients with chronic heart failure after myocardial infarction. AB - BACKGROUND: We sought to determine the safety and preliminary efficacy of transcatheter intramyocardial administration of myoblasts in patients with heart failure (HF). METHODS: MARVEL is a randomized placebo-controlled trial of image guided, catheter-based intramyocardial injection of placebo or myoblasts (400 or 800 million) in patients with class II to IV HF and ejection fraction <35%. Primary end points were frequency of serious adverse events (safety) and changes in 6-minute walk test and Minnesota Living With HF score (efficacy). Of 330 patients intended for enrollment, 23 were randomized (MARVEL-1) before stopping the study for financial reasons. RESULTS: At 6 months, similar numbers of events occurred in each group: 8 (placebo), 7 (low dose), and 8 (high dose), without deaths. Ventricular tachycardia responsive to amiodarone was more frequent in myoblast-treated patients: 1 (placebo), 3 (low dose), and 4 (high dose). A trend toward improvement in functional capacity was noted in myoblast-treated groups (Delta6-minute walk test of -3.6 vs +95.6 vs +85.5 m [placebo vs low dose vs high dose; P = .50]) without significant changes in Minnesota Living With HF scores. CONCLUSIONS: In HF patients with chronic postinfarction cardiomyopathy, transcatheter administration of myoblasts in doses of 400 to 800 million cells is feasible and may lead to important clinical benefits. Ventricular tachycardia may be provoked by myoblast injection but appears to be a transient and treatable problem. A large-scale outcome trial of myoblast administration in HF patients with postinfarction cardiomyopathy is feasible and warranted. PMID- 21982658 TI - Incidence and predictors of heart failure following percutaneous coronary intervention in ST-segment elevation myocardial infarction: the HORIZONS-AMI trial. AB - BACKGROUND: Congestive heart failure (CHF) is a major source of morbidity, mortality, and health-care resource consumption. However, the incidence of symptomatic CHF after primary percutaneous coronary intervention (PCI) for ST segment elevation myocardial infarction (STEMI) has rarely been fully reported. We therefore examined the early and late incidence, predictors, and implications of CHF in the large-scale, prospective, randomized HORIZONS-AMI trial. METHODS AND RESULTS: New York Heart Association (NYHA) functional classification was prospectively collected from patient-level data at baseline, 30 days, 6 months, and at 1 and 2 years from 3,343 patients with STEMI undergoing PCI at 123 centers in 11 countries. The baseline incidence of CHF (before the index STEMI) was 2.6%, increasing to 4.6% 1 month after primary PCI (P < .0001), 4.7% at 1 year, and 5.1% at 2 years. The incidence of NYHA class III/IV symptoms was 0.4% at baseline and 0.8% at 2 years (P = .03). CHF at 1 year was associated with diabetes (P < .0001), dyslipidemia (P = .009), previous MI (P < .0001), previous revascularization (P = .01), anterior STEMI (P = .02), and baseline TIMI grade 0 flow (P = .01) but not procedural anticoagulation with bivalirudin versus heparin + GPIIb/IIIa inhibitors (P = .93) or use of drug-eluting versus bare metal stents (P = .66). Among patients in whom CHF was not present at baseline but developed after PCI, the rate of all-cause mortality was significantly higher during 2-year follow-up (7.3% vs 2.0%, P < .0001), as was cardiac mortality (2.4% vs 0.8%, P = .004), reinfarction (9.4% vs 5.2%, P = .0009), stent thrombosis (7.0% vs 3.8%, P = .007), and ischemic target vessel revascularization (19.4% vs 11.8%, P < .0001). CONCLUSION: In the HORIZONS-AMI trial, the development of new-onset CHF within 2 years after contemporary PCI, although infrequent, was associated with significantly increased rates of mortality and major adverse ischemic events. PMID- 21982659 TI - Is the measurement of left ventricular ejection fraction the proper end point for cell therapy trials? An analysis of the effect of bone marrow mononuclear stem cell administration on left ventricular ejection fraction after ST-segment elevation myocardial infarction when evaluated by cardiac magnetic resonance imaging. AB - BACKGROUND: The measurement of left ventricular (LV) ejection fraction (LVEF) is a strong predictor of cardiovascular adverse events and mortality in patients with LV dysfunction and has become the most common primary end point in cardiovascular cell therapy trials after ST-segment elevation myocardial infarction (STEMI). Multiple small trials have been performed using bone marrow mononuclear stem cells (BMCs) in this setting with several meta-analyses demonstrating that BMC administration results in a small improvement in LVEF and may attenuate adverse LV remodeling. However, individual trial results have not been uniform, and the measurement of LVEF in these trials has relied on a variety of imaging techniques including LV angiograpnhy, single-photon emission computed tomography, echocardiography, or cardiac magnetic resonance imaging (cMRI). METHODS: Because cMRI provides the most accurate measurement of LVEF, LV volumes, and infarct size in patients after STEMI, we reviewed all randomized cardiovascular stem cell trials (N = 10) that administered intracoronary BMCs versus placebo/control to 686 patients after primary percutaneous coronary intervention treatment of STEMI that used cMRI as their principal imaging measurement of LVEF at baseline and 3 to 6 months later. RESULTS: Administration of BMCs was associated with a nonsignificant 0.9% +/- 0.8% absolute increase in LVEF compared with placebo or control (95% CI -0.7 to 2.4) with a small but nonsignificant decrease LV end-diastolic and LV end-systolic volumes (LV end diastolic volume -1.1 +/- 1.5 mL/m(2), LV end-systolic volume -1.6 +/- 1.4 mL/m(2)). Although infarct size uniformly decreased over time, the reduction was not improved by BMC administration (-0.3 +/- 1.7 g). CONCLUSIONS: The benefit of BMC administration after STEMI on LVEF, LV volumes, and infarct size is small when assessed by cMRI. PMID- 21982661 TI - Cardiac structure and function, remodeling, and clinical outcomes among patients with diabetes after myocardial infarction complicated by left ventricular systolic dysfunction, heart failure, or both. AB - AIMS: The mechanisms responsible for the increased risk of heart failure (HF) post-myocardial infarction (MI) may differ between patients with versus without diabetes. We hypothesized that after high-risk MI, patients with diabetes would demonstrate patterns of remodeling that are suggestive of reduced ventricular compliance and that are associated with an increased risk of death or HF. METHODS AND RESULTS: We performed quantitative echocardiographic analysis in 153 patients with diabetes and 451 patients without diabetes enrolled in the VALIANT Echo study. Diabetes was associated with a higher risk of death or HF in age-adjusted models (hazard ratio 1.44, 95% CI 1.04-2.00, P = .028). Diabetic patients were similar to nondiabetic patients with respect to left ventricular (LV) volume and ejection fraction but had higher LV mass index (104.1 +/- 27.5 vs 97.1 +/- 28.6 g/m(2), P = .009), relative wall thickness (0.41 +/- 0.08 vs 0.38 +/- 0.07, P < .0001), and left atrial volume index (LAVi) (26.2 +/- 8.1 vs 24.0 +/- 8.2 mL/m(2), P = .008)-all parameters that were significantly related to the risk of death or HF hospitalization. Changes in LV volume and ejection fraction from baseline to 20 months were not different, although diabetic patients demonstrated greater increase in LAVi (4.4 +/- 7.7 vs 2.2 +/- 6.7 mL/m(2), P = .01). CONCLUSIONS: After high-risk MI, diabetic patients were at higher risk of death or HF and demonstrated greater baseline LV mass index, relative wall thickness, and LAVi as well as greater left atrial enlargement at 20-month follow-up. These findings suggest greater baseline concentric remodeling and long-term elevation in LV diastolic pressure post-MI among diabetic patients, which may partially mediate this risk. PMID- 21982660 TI - In women with symptoms of cardiac ischemia, nonobstructive coronary arteries, and microvascular dysfunction, angiotensin-converting enzyme inhibition is associated with improved microvascular function: A double-blind randomized study from the National Heart, Lung and Blood Institute Women's Ischemia Syndrome Evaluation (WISE). AB - BACKGROUND: We investigated the role of the renin-angiotensin system in women with signs and symptoms of ischemia without obstructive coronary artery disease (CAD). Although microvascular dysfunction has been suggested to explain this syndrome and recently was found to predict adverse outcomes, the mechanisms and treatments remain unclear. METHODS: In a substudy within the WISE, 78 women with microvascular dysfunction (coronary flow reserve [CFR] <3.0 following adenosine) and no obstructive CAD were randomly assigned to either an angiotensin-converting enzyme inhibition (ACE-I) with quinapril or a placebo treatment group. The primary efficacy parameter was CFR at 16 weeks adjusted for baseline characteristics and clinical site. The secondary response variable was freedom from angina symptoms assessed using the Seattle Angina Questionnaire. RESULTS: A total of 61 women completed the 16-week treatment period with repeat CFR measurements, and treatment was well tolerated. For the primary outcome, at 16 weeks, CFR improved more with ACE-I than placebo (P < .02). For the secondary outcome of symptom improvement, ACE-I treatment (P = .037) and CFR increase (P = .008) both contributed. CONCLUSIONS: Microvascular function improves with ACE-I therapy in women with signs and symptoms of ischemia without obstructive CAD. This improvement is associated with reduction in angina. The beneficial response of the coronary microvasculature was limited to women with lower baseline CFR values, suggesting that the renin-angiotensin system may be more involved among women with more severe microvascular defects. PMID- 21982662 TI - Improvement in use of anticoagulation therapy in patients with ischemic stroke: results from Get With The Guidelines-Stroke. AB - BACKGROUND: Anticoagulation therapy reduces thromboembolic events in patients with atrial fibrillation (AF) and has a class I indication for ischemic stroke patients with AF and no contraindications. We determined the patient and hospital level characteristics associated with an increased use of anticoagulation, including participation in the Get With The Guidelines-Stroke (GWTG-Stroke) Program. METHODS: We assessed the use of anticoagulation at hospital discharge in eligible AF patients with stroke or transient ischemic attack (TIA) at 1,354 participating hospitals between April 1, 2003, and April 1, 2010. RESULTS: Patients with AF (n = 197,778) represented 20.5% of patients with ischemic stroke/TIA. Among patients with AF, 47.6% (n = 94,119) were deemed eligible for anticoagulation, and of these, 94.0% were discharged on therapy. Older patients, African American or Hispanic patients, and those with diabetes were less likely to receive anticoagulation. Hospitals with a higher volume of patients with stroke were more likely to treat with anticoagulation. The Joint Commission Primary Stroke Centers were also more likely to treat eligible patients (odds ratio 2.16, 95% CI 1.82-2.56, P < .0001). From 2003 to 2010, contraindications to anticoagulation therapy declined from 69.7% to 28.4% (P < .0001 for trend). Anticoagulation among eligible patients improved from 88.4% to 95.2% (P < .0001) for 7 years of participation. Time in GWTG-Stroke was associated with improved anticoagulation use (adjusted odds ratio per year in program, 1.11, 95% CI 1.06 1.16, P < .001). CONCLUSIONS: Use of anticoagulation among stroke patients with AF has increased to very high levels overall in GWTG-Stroke over time. Future efforts should focus on improving use among selected populations. PMID- 21982663 TI - Cluster-randomized trial to evaluate the effects of a quality improvement program on management of non-ST-elevation acute coronary syndromes: The European Quality Improvement Programme for Acute Coronary Syndromes (EQUIP-ACS). AB - BACKGROUND: Registries have shown that quality of care for acute coronary syndromes (ACS) often falls below the standards recommended in professional guidelines. Quality improvement (QI) is a strategy to improve standards of clinical care for patients, but the efficacy of QI for ACS has not been tested in randomized trials. METHODS: We undertook a prospective, cluster-randomized, multicenter, multinational study to evaluate the efficacy of a QI program for ACS. Participating centers collected data on consecutive admissions for non-ST elevation ACS for 4 months before the QI intervention and 3 months after. Thirty eight hospitals in France, Italy, Poland, Spain, and the United Kingdom were randomized to receive the QI program or not, 19 in each group. We measured 8 in hospital quality indicators (risk stratification, coronary angiography, anticoagulation, beta-blockers, statins, angiotensin-converting enzyme inhibitors, and clopidogrel loading and maintenance) before and after the intervention and compared composite changes between the QI and non-QI groups. RESULTS: A total of 2604 patients were enrolled. The absolute overall change in use of quality indicators in the QI group was 8.5% compared with 0.8% in the non QI group (odds ratio for achieving a quality indicator in QI versus non-QI 1.66, 95% CI 1.43-1.94; P < .001). The main changes were observed in the use of risk stratification and clopidogrel loading dose. CONCLUSIONS: The QI strategy resulted in a significant improvement in the quality indicators measured. This type of QI intervention can lead to useful changes in health care practice for ACS in a wide range of settings. PMID- 21982664 TI - Efficacy and safety after cessation of treatment with the cholesteryl ester transfer protein inhibitor anacetrapib (MK-0859) in patients with primary hypercholesterolemia or mixed hyperlipidemia. AB - This report describes the lipid and safety data collected during an off-drug period that followed 8 weeks of treatment with the cholesteryl ester transfer protein inhibitor, anacetrapib (ANA). A total of 589 patients with primary hypercholesterolemia or mixed hyperlipidemia were randomized to placebo, atorvastatin (ATV) 20 mg, and varying doses of ANA, provided as monotherapy or coadministered with ATV 20 mg daily. Patients were treated for 8 weeks, followed by an 8-week follow-up period, during which ANA was switched to placebo. At week 16 (8 weeks after ANA was stopped), persistent reductions in low-density lipoprotein cholesterol (LDL-C) were evident for the monotherapy groups receiving ANA 150 and 300 mg (-9.3% and -15.3%, respectively), and residual increases in high-density lipoprotein cholesterol (HDL-C) were observed for the monotherapy groups receiving ANA 40 mg (18.6%), 150 mg (40.5%), and 300 mg (43.4%). The effects on apolipoprotein B and apolipoprotein A-I were consistent with the changes observed for LDL-C and HDL-C, respectively. Corresponding residual changes in LDL-C and HDL-C were also noted in the ATV coadministration groups at the similar doses of ANA compared with ATV 20 mg alone. Residual plasma drug levels accompanied by reductions in cholesteryl ester transfer protein activity were observed at week 16 and may account for the alterations in plasma lipids 8 weeks after cessation of ANA. PMID- 21982665 TI - Adherence to the Mediterranean diet in relation to acute coronary syndrome or stroke nonfatal events: a comparative analysis of a case/case-control study. AB - BACKGROUND: Although the role of Mediterranean diet on cardiovascular disease prevention has long been evaluated and understood, its association with the development of stroke has been rarely examined. The aim of the present work was to comparatively evaluate the association between adherence to the Mediterranean diet and the development of an acute coronary syndrome (ACS) or ischemic stroke. METHODS: During the period from 2009 to 2010, 1,000 participants were enrolled; 250 were consecutive patients with a first ACS, 250 were consecutive patients with a first ischemic stroke, and 500 population-based, control subjects, 1-for-1 matched to the patients by age and sex. Sociodemographic, clinical, psychological, dietary, and other lifestyle characteristics were measured. Adherence to the Mediterranean diet was assessed by the validated MedDietScore (theoretical range 0-55). RESULTS: After various adjustments were made, it was observed that for each 1-of-55-unit increase of the MedDietScore, the corresponding odds ratio for having an ACS was 0.91 (95% CI 0.87-0.96), whereas regarding stroke, it was 0.88 (95% CI 0.82-0.94). CONCLUSIONS: The present work extended the current knowledge about the cardioprotective benefits from the adoption of the Mediterranean diet by showing an additional protective effect on ischemic stroke development. PMID- 21982666 TI - Frequency and correlates of treatment intensification for elevated cholesterol levels in patients with cardiovascular disease. AB - BACKGROUND: Although current performance measures define low-density-lipoprotein cholesterol (LDL-C) levels <100 mg/dL in patients with cardiovascular disease (CVD) as good quality, they provide a snapshot and do not address whether treatment intensification was performed to manage elevated LDL-C levels. METHODS: We determined the proportion of patients with CVD (n = 22,888) with LDL-C <100 mg/dL and the proportion with uncontrolled LDL-C levels (>=100 mg/dL) who received treatment intensification within the 45-day follow-up in a Veterans Affairs Network. We evaluated facility, provider, and patient correlates of treatment intensification. RESULTS: Low-density-lipoprotein cholesterol levels were at goal in 16,350 (71.4%) patients. An additional 2,093 (one third of those eligible for treatment intensification) received treatment intensification. Controlling for clustering between facilities and patient's illness severity: history of diabetes (odds ratio [OR] 1.15, 95% CI 1.01-1.32), hypertension (OR 1.19, 95% CI 1.01-1.42), good medication adherence (OR 2.20, 95% CI 1.91-2.54), and a higher number of lipid panels (OR 1.20, 95% CI 1.14-1.27) were associated with treatment intensification. Patients older than 75 years (OR 0.65, 95% CI 0.56-0.75) and women (OR 0.66, 95% CI 0.43-1.00) were less likely to receive treatment intensification. Teaching status of the facility, physician or specialist primary care provider, and patient's race were not associated with treatment intensification. CONCLUSIONS: Only one third of the CVD patients with elevated LDL-C received treatment intensification. Diabetic and hypertensive patients were more likely to receive treatment intensification, whereas, older patients, female patients, and patients with poor medication adherence were less likely to receive treatment intensification. Our findings highlight areas for quality improvement initiatives. PMID- 21982667 TI - Prasugrel overcomes high on-clopidogrel platelet reactivity in chronic coronary artery disease patients more effectively than high dose (150 mg) clopidogrel. AB - BACKGROUND: High on-treatment platelet reactivity (HTPR) is present in a substantial percentage of patients on chronic clopidogrel treatment and may have prognostic implications. Strategies to optimize platelet inhibition in such patients are not clear. METHODS: We performed a prospective, single-center, single-blinded, investigator-initiated randomized, crossover study of platelet inhibition by prasugrel 10 mg/day versus high-dose 150 mg/day clopidogrel, with a 14 day treatment period, in 31 patients with HTPR (out of 99 screened, 31.3%) while on chronic (>= 12 months) treatment with clopidogrel. All patients had stable coronary artery disease and 87.1% of them had a prior percutaneous coronary intervention. Platelet reactivity (PR) was assessed by the VerifyNow assay measured in platelet reactivity units (PRU). RESULTS: The primary end point of PR at the end of the two treatment periods was lower in patients receiving prasugrel compared with high dose clopidogrel ( least squares estimate 148.1, 95% CI 127.1-169.2 and 219.8, 95% CI 198.6-240.9 respectively, P < .001). The secondary end point of HTPR rate was lower for prasugrel compared with clopidogrel, 11.5% vs 46.3%, P = .003. CONCLUSIONS: Prasugrel appears more effective than double clopidogrel in inhibiting PR in patients with HTPR following chronic clopidogrel treatment. PMID- 21982668 TI - A meta-analysis of specifically designed randomized trials of sirolimus-eluting versus paclitaxel-eluting stents in diabetic patients with coronary artery disease. AB - BACKGROUND: There is an ongoing debate on the optimal drug-eluting stent (DES) in diabetic patients with coronary artery disease. We addressed this issue by making a synthesis of the available evidence on the relative long-term efficacy and safety of sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES) in these patients. METHODS: Individual patient data were analyzed from 6 randomized trials specifically designed to compare SES with PES in diabetic patients. In total, 1183 patients were followed up for a median of 3.9 years (25th, 75th percentiles 3.4-4.5 years). The primary efficacy end point was target lesion revascularization (TLR). The composite of death and myocardial infarction (MI) was the primary safety end point. Stent thrombosis was a secondary end point. Overall hazard ratios (HRs) with 95% CIs were calculated as summary estimates. RESULTS: No significant heterogeneity was seen across the 6 randomized trials for all analyzed events. Sirolimus-eluting stent was associated with a significant reduction in the risk of TLR (HR 0.65 [0.47-0.91], P = .01). No significant differences were observed regarding the risk of death or MI (HR 1.04 [0.74-1.45], P = .83) and stent thrombosis (HR 1.00 [0.31-3.30], P = .67). Mortality was also not affected by the type of DES (HR 0.95 [0.65-1.39], P = .79). CONCLUSIONS: In diabetic patients with coronary artery disease, SES leads to a sustained reduction in the risk of TLR compared with PES. Both these DES types are, however, comparable with respect to the risk of stent thrombosis, MI, or death over long-term follow-up. PMID- 21982669 TI - Predictors of fatal and nonfatal cardiovascular events in patients with type 2 diabetes mellitus, chronic kidney disease, and anemia: an analysis of the Trial to Reduce cardiovascular Events with Aranesp (darbepoetin-alfa) Therapy (TREAT). AB - AIMS: This study aims to examine predictors of cardiovascular mortality and morbidity in patients with chronic kidney disease (CKD). Individuals with the triad of diabetes, CKD, and anemia represent a significant proportion of patients with cardiovascular disease and are at particularly high risk for adverse outcomes. METHODS AND RESULTS: Using Cox proportional hazards models, we identified independent predictors of the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for myocardial ischemia, or heart failure (HF) in 3,847 patients in the TREAT, 961 (25%) of whom experienced this outcome. The predictors (ranked by chi(2) value) were prior HF (hazard ratio [HR] 1.74, 95% CI 1.51-2.01), age (HR 1.03, 95% CI 1.02-1.04 per year), log urine protein/creatinine ratio (HR 1.19, 95% CI 1.13-1.26 per log unit ), C-reactive protein >=6.6 mg/L (HR 1.44, 95% CI 1.23-1.69, compared with C-reactive protein <=3.0 mg/L), and abnormal electrocardiogram (HR 1.42, 95% CI 1.21-1.66 ), all P < .0001. Addition of cardiac-derived biomarkers (subset of first 1,000 patients enrolled) significantly enhanced risk estimation, with N-terminal pro B-type natriuretic peptide becoming the highest ranked predictor of outcome (HR 1.30, 95% CI 1.15-1.46 per log unit, P < .001) and troponin T providing additional predictive information. These biomarkers improved risk classification in 17.8% (9.4%-26.2%) of patients. CONCLUSION: In patients with diabetes, CKD, and anemia, cardiovascular risk is most strongly predicted by age, history of HF, C-reactive protein, urinary protein/creatinine ratio, abnormal electrocardiogram, and 2 specific cardiac biomarkers, serum N-terminal pro B-type natriuretic peptide and troponin T, which are elevated in many. These findings suggest ways to improve cardiovascular risk stratification of patients with predialysis CKD, support the concept of cardiorenal syndrome, and may help target therapy. PMID- 21982670 TI - Cognitive decline and ischemic microlesions after coronary catheterization. A comparison to coronary artery bypass grafting. AB - BACKGROUND: Postinterventional cognitive dysfunction (PICD) is a known complication of coronary artery bypass grafting (CABG). However, it is largely unknown whether PICD occurs after coronary catheterization. METHODS: Neuropsychologic data were obtained from 37 patients who received coronary catheterization and 47 patients who underwent elective CABG at baseline and 3 months after the interventions. The outcomes were contrasted to 33 healthy volunteers, using analysis of covariance with baseline scores as covariates. Cerebral magnetic resonance imaging with diffusion-weighted imaging (DWI) sequences was performed in 30 catheter and 39 CABG patients 2 to 4 days after the procedures. RESULTS: The rate of acute ischemic lesions amounted to 3.3% in the catheter group and to 17.9% in the CABG group. Postinterventional cognitive dysfunction was detected in 2 (of 10) tests in the catheter group as compared with the healthy controls (verbal memory: total recall, t = -2.61 (P = .005) and nonverbal memory, t = -2.60 [P = .005]). The CABG group showed PICD in 7 of 10 tests as compared with the healthy controls (statistics ranging from t = -1.95 [P = .027] to t = -5.14 [P < .001]). Scores of depression/anxiety and health-related quality of life were not associated with PICD (P > .05). CONCLUSIONS: As compared with CABG, PICD and cerebral lesions appear to be substantially milder after coronary catheter intervention, but not negligible. PMID- 21982671 TI - Downstream coronary effects of drug-eluting stents. AB - BACKGROUND: Antiproliferative agents used in drug-eluting stents (DES) attenuate atherosclerosis, yet DES implantation has been linked to endothelial dysfunction. The downstream effects of DES on new lesion formation have not been previously directly examined. We sought to compare the development of de novo stenoses and need for treatment in the downstream coronary vessel of patients treated with DES or a bare-metal stent. METHODS: Angiographic images and procedural information were prospectively collected on 463 adults who underwent implantation of a single stent in a proximal coronary artery, had an appropriate control vessel for comparison, and subsequently returned for intervention. Propensity matching identified 89 pairs of patients. End points were defined as angiographic identification of a de novo stenosis or need for secondary intervention in the downstream vessel within 12 months of initial intervention. RESULTS: In the overall (P < .01) and propensity-matched cohort (P = .01), there was reduced risk of new lesions downstream to DES. No difference was seen in respective control vessels (P = .14 and P = .99). A reduced need for downstream intervention with DES was seen in both the overall (P = .01) and propensity-matched cohorts (P = .04). No difference was seen in the control vessels (P = .98 and P = .36). Multivariate proportional hazards modeling of known atherosclerosis risk factors identified stent type as the sole predictor for downstream lesions (P < .01) and downstream events (P = .02). CONCLUSIONS: Patients receiving DES appear less likely to develop downstream stenoses and events compared with patients receiving bare-metal stents, suggesting beneficial downstream drug delivery. PMID- 21982672 TI - Appropriateness use criteria for transthoracic echocardiography: relationship with radiology benefit managers preauthorization determination and comparison of the new (2010) criteria to the original (2007) criteria. AB - BACKGROUND: In response to growth in cardiac imaging, medical societies have published appropriateness use criteria (AUC) and payers have introduced preauthorization mandates, largely through radiology benefits managers (RBM). The correlation of algorithms used to determine preauthorization with the AUC is unknown. In addition, studies applying the 2007 AUC for transthoracic echocardiography revealed that many echocardiograms could not be classified. We sought to examine the impact of the revised 2010 AUC on appropriateness ratings of transthoracic echocardiograms previously classified by the 2007 AUC and the relationship of preauthorization determination to AUC rating. METHODS: We reclassified indications for transthoracic echocardiography as appropriate, inappropriate, uncertain, or unclassifiable using the 2010 AUC in the same 625 patients previously reported using 2007 AUC. We also evaluated the relationship between preauthorization status by 2 RBM precertification algorithms and appropriateness rating by 2007 AUC. RESULTS: The appropriateness classification of 148 (24%) transthoracic echocardiograms was changed by the updated AUC (P < .001). The number of unclassifiable echocardiograms was markedly reduced from 99 (16%) to 8 (1%), and more echocardiograms were classified as inappropriate (95 [15%] vs 45 [7%]) or uncertain (43 [7%] vs 0 [0%]). Limited correlation between the 2007 AUC rating and RBM preauthorization determinations was noted, with only moderate agreement with RBM no. 1 (90%, kappa = 0.480, P < .001) and poor agreement with RBM no. 2 (72%, kappa = 0.177, P < .001). CONCLUSION: The updated AUC (2010) provide enhanced clinical value compared with 2007 AUC. There is limited agreement between RBM preauthorization determination and 2007 AUC rating. PMID- 21982673 TI - Effect of informed consent format on patient anxiety, knowledge, and satisfaction. AB - BACKGROUND: Multiple formats have been used to deliver information needed for informed consent before a medical procedure, but data comparing formats are conflicting. METHODS: Sixty-three patients (45 men, age 61 +/- 16 years) undergoing an initial diagnostic cardiac electrophysiology study were randomly assigned to 1 of 3 groups: oral, written, or video informed consent using a standardized text for all 3 formats. Anxiety levels were assessed with the Spielberger State-Trait Anxiety Inventory (STAI), and questionnaires were used to assess patient comprehension and satisfaction with the informed consent process. Physician time needed to obtain informed consent was also measured. The effect of informed consent format on anxiety state was evaluated by comparing STAI before and after consent. Multivariable analysis was performed to assess the effects of baseline characteristics on the state anxiety scores. RESULTS: For the oral, written, and video formats, the mean anxiety trait scores were 39 +/- 9, 34 +/- 8, and 31 +/- 7, respectively (P = .005), and baseline anxiety state scores were 49 +/- 12, 37 +/- 12, and 36 +/- 11, respectively (P = .0006). None of the formats had a significant effect on patient anxiety state after consent was obtained. After the procedure, anxiety state declined (P < .0001). There were no differences among the comprehension scores, and patient satisfaction was equivalent among formats. The oral format required the longest physician time (P = .06). CONCLUSION: For electrophysiologic testing, all 3 formats have similar effects on anxiety and produce equivalent patient comprehension. The oral format requires more physician time. Given the standardization achievable with a written or video format, physicians may consider these options to facilitate obtaining informed consent. PMID- 21982674 TI - Training providers in hypertension guidelines: cost-effectiveness evaluation of a continuing medical education program in South Carolina. AB - BACKGROUND: Translation of published guidelines to clinical practice through continuing medical education (CME) can be effective at changing provider practice patterns and patient outcomes. Yet, cost-effectiveness analyses of CME interventions are rare. This study analyzed the cost-effectiveness of a CME program for improving patient hypertension outcomes relative to usual care. METHODS: A CME, conducted by the Carolinas and Georgia chapter of the American Society of Hypertension, the Medical University of South Carolina, and the Heart Disease and Stroke Prevention Division of the South Carolina Department of Health and Environmental Control, trained primary care providers in evidence-based guidelines for hypertension prevention and control. A cost-effectiveness simulation model was created with inputs from primary data collection of program costs and secondary data analysis of the Hypertension Initiative Database for years 2000 through 2008. The data analysis consisted of a convenience sample of 8,183 patients in the Hypertension Initiative Database who saw a CME-trained provider at least once before and after the provider's training. Control patients saw providers who did not attend a CME program and were matched to CME patients using propensity score matching. RESULTS: Incremental life-years gained (LYG) for CME compared with no intervention were 0.003 per patient. The incremental cost effectiveness ratio was $39,494 ($19,184-$73,864) per LYG under optimistic assumptions and $54,755 ($32,423-$95,728) per LYG under pessimistic assumptions. These results were most sensitive to changes in the effectiveness of the intervention on systolic blood pressure. CONCLUSIONS: The intervention is likely a cost-effective strategy to address hypertension in a real-world setting and can serve as a model for future innovations in hypertension prevention. PMID- 21982675 TI - Letter to the editor regarding "Outcomes in patients with chronicity of left bundle-branch block with possible acute myocardial infarction". PMID- 21982676 TI - Regarding "Depressive symptoms are related to progression of coronary calcium in midlife women: the Study of Women's Health Across the Nation (SWAN) Heart Study". PMID- 21982678 TI - Escherichia coli virulence genes profile of surface waters as an indicator of water quality. AB - We compared the presence of 58 known virulence genes (VGs) associated with Escherichia coli strains causing intestinal (InPEC) and extra-intestinal (ExPEC) infections in three estuarine, four brackish and 13 freshwater sites during the dry and wet seasons. The most common VGs observed in water samples during the dry season belonged to ExPEC (traT; 80% and ompA; 70%) whilst east1 (70%) gene was the most common among InPEC. More types of VGs were observed in water samples during wet season and included those found among InPEC (e.g. eaeA; 100%; fyuA, 90%; paa, 65%; cdt, 60%; and stx(2), 60%) and ExPEC (e.g. iroN(E.coli), 90%; iss, 90% and kpsMTII, 80%). Eight VGs were found exclusively in the wet season, of which four were found in all three water types indicating their association with storm-water run off. The number of VGs associated with ExPEC were significantly (P < 0.05) higher in only brackish and estuarine waters during the wet season compared to the dry season. There was no correlation between the number of E. coli and the presence of VGs in any of the water types in both seasons but we found similarities in VG profiles of sites with similar land uses. PMID- 21982679 TI - Nutrient gradients in a granular activated carbon biofilter drives bacterial community organization and dynamics. AB - The quality of drinking water is ensured by hygienic barriers and filtration steps, such as ozonation and granular activated carbon (GAC) filtration. Apart from adsorption, GAC filtration involves microbial processes that remove biodegradable organic carbon from the ozonated ground or surface water and ensures biological stability of the treated water. In this study, microbial community dynamics in were monitored during the start-up and maturation of an undisturbed pilot-scale GAC filter at 4 depths (10, 45, 80 and 115 cm) over a period of 6 months. New ecological tools, based on 16S rRNA gene-DGGE, were correlated to filter performance and microbial activity and showed that the microbial gradients developing in the filter was of importance. At 10 cm from the top, receiving the freshly ozonated water with the highest concentration of nutrients, the microbial community dynamics were minimal and the species richness remained low. However, the GAC samples at 80-115 cm showed a 2-3 times higher species richness than the 10-45 cm samples. The highest biomass densities were observed at 45-80 cm, which corresponded with maximum removal of dissolved and assimilable organic carbon. Furthermore, the start-up period was clearly distinguishable using the Lorenz analysis, as after 80 days, the microbial community shifted to an apparent steady-state condition with increased evenness. This study showed that GAC biofilter performance is not necessarily correlated to biomass concentration, but rather that an elevated functionality can be the result of increased microbial community richness, evenness and dynamics. PMID- 21982680 TI - A novel echocardiographic parameter for predicting the ischemic etiology of cardiomyopathy and its prognosis in patients with congestive heart failure. AB - BACKGROUND: Although previous studies have established the ability of mitral annular velocities and velocity dispersion indices to differentiate between ischemic cardiomyopathy (ICM) and nonischemic cardiomyopathy, prospective data are lacking on both the use of heterogeneity of mitral annular velocities to predict the ischemic etiology in patients with left ventricular dysfunction and further cardiovascular prognosis. METHODS: A total of 232 patients with left ventricular ejection fractions < 40% were admitted between 2008 and 2010. Doppler tissue imaging was performed on six mitral annular sites for three consecutive beats and then averaged for each site. Systolic (Vs') and early (Ve') and late (Va') diastolic mitral annular velocity dispersion indices among the six mitral annular sites were calculated. RESULTS: Ve' was a significant predictor (P < .01) of ICM in multivariate logistic regression models adjusted for clinical variables and conventional echocardiography. The optimal cutoff value for predicting ICM was Ve' >= 16.7 with an area under the receiver operating characteristic curve of 0.92. Its sensitivity and specificity were 87% and 85%, respectively. During follow-up (median, 32 months), 64 participants experienced cardiac mortality. The adjusted hazard ratio in Cox proportional-hazards analysis for death in the third tertile in comparison with the first tertile of Ve' was 2.92 (P = .02). CONCLUSIONS: A high degree of heterogeneity of e', expressed as Ve', provides incremental value over clinical variables and conventional echocardiography to predict the prevalence of low left ventricular ejection fractions patients with ICM. Furthermore, elevated Ve' could also identify patients at a high risk for cardiac mortality. PMID- 21982681 TI - Swallowing dysfunction after prolonged intubation: analysis of risk factors in trauma patients. AB - BACKGROUND: The clinical significance of post-extubation swallowing dysfunction (PSD) is profound, resulting in both increased morbidity and mortality. Specific risk factors have not been described in an injured patient cohort. The purpose of this pilot study was to elucidate independent factors that predict PSD in this population. METHODS: A retrospective cohort analysis was performed on 150 consecutive trauma patients intubated for more than 48 hours. Assessment of swallowing function after extubation was performed by a simple bedside speech pathology evaluation. Patients then were divided into 2 groups: those with and those without PSD. Backwards stepwise logistic regression analysis then was used to determine independent predictors of PSD after controlling for important injury characteristics and patient demographics. RESULTS: The incidence of PSD in our study cohort was 41%. Patients with PSD, although older than non-PSD patients (48 vs 37.5 y; P = .001), were similar with respect to admission Glasgow coma score (GCS) and injury severity score. Regression analysis revealed that age older than 55 years (odds ratio, 2.60; P = .037; 95% confidence interval, 1.1-6.4) and ventilator days (odds ratio, 1.14; P = .001; 95% confidence interval, 1.1-1.2) were significant independent risk factors for PSD. Interpretation of these odds ratios revealed that those patients older than age 55 had more than a 2.5-fold greater risk of PSD. The risk increased by 14% for every day a patient required intubation. There was no significant association between PSD and injury severity score, GCS, presence of medical comorbidities, or development of nosocomial pneumonia. CONCLUSIONS: PSD is a common occurrence in trauma patients. Age older than 55 years and ventilator days are independent risk factors for PSD. Injury severity, altered GCS upon arrival, comorbidities, and nosocomial pneumonia were not independent risk factors for PSD in our cohort. These results suggest that older patients with extended intensive care unit stays and ventilator requirements may benefit from early swallowing evaluation. PMID- 21982683 TI - YHHU0895, a novel synthetic small-molecule microtubule-destabilizing agent, effectively overcomes P-glycoprotein-mediated tumor multidrug resistance. AB - P-glycoprotein-mediated multidrug resistance (MDR) is a major limiting factor in the efficacy of most microtubule-targeting agents. Here, we investigated the novel, synthetic, and small-molecule microtubule-destabilizing agent, 2-(2-amino 5-(1-ethyl-1H-indol-5-yl) pyrimidin-4-yl) phenol (YHHU0895), for its anti-tumor activity and potential for overcoming P-glycoprotein-mediated MDR. YHHU0895 inhibited purified tubulin polymerization through binding to tubulin at the colchicine-binding site and significantly inhibited human tumor cell proliferation. Notably, P-glycoprotein-overexpressing KBV200 and K562/ADR cells, which are strongly resistant to colchicine, vinorelbine and paclitaxel, were sensitive to YHHU0895 both in vitro and in vivo. These findings indicate that YHHU0895 is a novel type of microtubule-destabilizing agent that has the potential for the treatment of patients with drug resistance mediated by P glycoprotein. PMID- 21982682 TI - Immunostimulatory CpG-DNA and PSA-peptide vaccination elicits profound cytotoxic T cell responses. AB - OBJECTIVE: Novel strategies for the treatment of advanced prostate cancer (CaP), including immunotherapy or gene therapy, are currently under evaluation with Sipuleucel-T as first FDA-approved immunotherapeutic. Here, we examine cytosine phosphorothioate-guanine (CpG)-DNA oligonucleotides (ODN) to boost cytokine responses and costimulatory molecule expression on murine bone marrow-derived dendritic cells (mBMDC). Furthermore, we evaluate the potency of a PSA-peptide based vaccine in combination with CpG-DNA to elicit specific cytotoxic T cell (CTL) responses. MATERIALS AND METHODS: mBMDC were stimulated with CpG-DNA (1668: 5'-TCCATGACGTTCCTGATGCT-3') or non-stimulatory control-ODN (1720: 5' TCCATGAGCTTCCTGATGCT-3'). Subsequently, expression of the costimulatory molecules CD40 and CD86 and induction of proinflammatory cytokines (interleukin (IL)-6 and IL-12) were analyzed. For induction of PSA-peptide specific CTL, female C57BL/6 mice were immunized with PSA-peptide 65-73 (HCIRNKSVI) alone or in combination with 1668 or 1720-ODN. In vivo cytotoxicity assay determined PSA-peptide specific cytotoxicity 1 week after vaccination. RESULTS: Treatment of mBMDC with stimulatory CpG-DNA ODN resulted in pronounced up-regulation of costimulatory molecule expression on mBMDC in a dose-dependent manner. CpG-ODN significantly increased production of IL-6 and IL-12 in mBMDC (P < 0.001). Induction of PSA peptide specific CTL responses in mice immunized with PSA-peptide and CpG-DNA were significantly greater than those of PSA-peptide and control-ODN immunized mice or PSA-peptide only vaccination. CONCLUSIONS: CpG-DNA acts as potent adjuvant for vaccination therapies and elicits profound PSA-peptide specific CTL responses in combination with an immunodominant PSA-peptide. CpG-ODN mediated immunotherapy represents a potentially inexpensive, safe, easy-to-produce, and easy-to-handle treatment alternative. Therefore, further evaluation of CpG-DNA in immunization therapies against CaP is warranted. PMID- 21982684 TI - EGFR and KRAS mutations and altered c-Met gene copy numbers in primary non-small cell lung cancer and associated stage N2 lymph node-metastasis. AB - This study aimed to detect mutations in EGFR and KRAS and alterations of c-Met gene copy number (GCN) changes in primary and lymph node-metastatic NSCLCs. The data showed the concordant rate of EGFR genotype in primary and stage N2 lymph node-metastatic tumors was 95.45%. c-Met GCN in stage N2 lymph nodes was significantly higher than that of the primary tumors (P=0.038). The results suggest both primary and lymph-node metastases have relatively consistent EGFR mutations and EGFR mutations are not relevant to changes in c-Met GCN. c-Met GCN was increased significantly in EGFR TKI-naive patients with lymph node-metastatic tumors. PMID- 21982685 TI - Lead optimization at C-2 and N-3 positions of thiazolidin-4-ones as HIV-1 non nucleoside reverse transcriptase inhibitors. AB - Based on rational drug design approach, a series of novel thiazolidin-4-ones bearing different aryl/heteroaryl moieties at position C-2 and N-3 are synthesized and evaluated as potent inhibitors for human immunodeficiency virus type-1 reverse transcriptase enzyme (HIV-1 RT). An in vitro HIV-1 RT assay showed that the compounds 4, 5, 6, 8, 12, 13, 14 and 17 have shown high inhibition of reverse transcriptase (75.41, 95.50, 98.07, 91.24, 85.27, 77.59, 84.11 & 76.49% inhibition) enzyme activity. Further, cell based assay showed that compounds 4, 5, 8 &12 are identified as the best compounds of the series (EC(50) ranged from 0.09 to 0.8 MUg/ml and 0.12 to 1.06 MUg/ml) against HIV-1 III(B) and HIV-1 ADA5 strains, respectively. Moreover, the compounds which were active against HIV-1 III(B) and HIV-1 ADA5 were also found to be active against primary isolates (EC(50) ranged from 0.10 to 1.55 MUg/ml against HIV-1 UG070 and 0.07 to 1.1 MUg/ml against HIV-1 VB59), respectively. Structure-activity relationship (SAR) studies demonstrated the importance of the lipophilic bulky substituent pattern on compact heteroaryl ring at N-3, replacement of C4' at C-2 phenyl by trivalent bioisosteric nitrogen and dihalo groups at C-2 aryl/heteroaryl of thiazolidin-4 ones is crucial for anti-HIV-1 activity. Molecular modeling of compounds 4, 5, 8 and 12 in complex with HIV-1 RT demonstrate that there is good correlation of results obtained from SAR studies. Therefore the compounds 4, 5, 8 and 12 may be considered as good candidates for further optimization of anti-HIV-1 activity. PMID- 21982686 TI - [ABCB1 polymorphisms in patients with Charcot-Marie-Tooth disease. A possible relationship with neurotoxicity due to cytostatic treatment]. PMID- 21982687 TI - In-hospital cardiology consultation and evidence-based care for nursing home residents with heart failure. AB - OBJECTIVES: To determine the association between cardiology consultation and evidence-based care for nursing home (NH) residents with heart failure (HF). PARTICIPANTS: Hospitalized NH residents (n = 646) discharged from 106 Alabama hospitals with a primary discharge diagnosis of HF during 1998-2001. DESIGN: Observational. MEASUREMENTS OF EVIDENCE-BASED CARE: Preadmission estimation of left ventricular ejection fraction (LVEF) for patients with known HF (n = 494), in-hospital LVEF estimation for HF patients without known LVEF (n = 452), and discharge prescriptions of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs or ARBs) to systolic HF (LVEF <45%) patients discharged alive who were eligible to receive those drugs (n = 83). Eligibility for ACEIs or ARBs was defined as lack of prior allergy or adverse effect, serum creatinine lower than 2.5 mg/dL, serum potassium lower than 5.5 mEq/L, and systolic blood pressure higher than 100 mm Hg. RESULTS: Preadmission LVEF was estimated in 38% and 12% of patients receiving and not receiving cardiology consultation, respectively (adjusted odds ratio [AOR], 3.49; 95% CI, 2.16-5.66; P < .001). In-hospital LVEF was estimated in 71% and 28% of patients receiving and not receiving cardiology consultation, respectively (AOR, 6.01; 95% CI, 3.69 9.79; P < .001). ACEIs or ARBs were prescribed to 62% and 82% of patients receiving and not receiving cardiology consultation, respectively (AOR, 0.24; 95% CI, 0.07-0.81; P = .022). CONCLUSION: In-hospital cardiology consultation was associated with significantly higher odds of LVEF estimation among NH residents with HF; however, it did not translate into higher odds of discharge prescriptions for ACEIs or ARBs to NH residents with systolic HF who were eligible for the receipt of these drugs. PMID- 21982688 TI - The cost-benefit of biosecurity measures on infectious diseases in the Egyptian household poultry. AB - Increased animal intensification presents with increasing risks of animal diseases. The Egyptian household poultry is peculiar in its management style and housing and this present with particular challenges of risk of infection to both the flock and humans. Biosecurity remains one of the most important means of reducing risks of infection in the household poultry, however not much information is available to support its feasibility at the household level of production. In this study financial feasibilities of biosecurity were modeled and evaluated based on certain production parameters. Risks of particular importance to the household poultry were categorized and highly pathogenic avian influenza H5N1 was the most risky disease while people-related risk was the most important risk category. It was observed that basic biosecurity measures were applicable in the household poultry and it would be 8.45 times better to implement biosecurity than to do nothing against HPAI H5N1; 4.88 times better against Newcastle disease and 1.49 times better against coccidiosis. Sensitivity analyses proved that the household poultry project was robust and would withstand various uncertainties. An uptake pathway for basic biosecurity was suggested. The outcome of this work should support decisions to implement biosecurity at the household sector of poultry production. PMID- 21982689 TI - Risk factors for hip-related clinical signs in a prospective cohort study of four large dog breeds in Norway. AB - We conducted a prospective cohort study including privately owned dogs from the breeds Newfondland (NF), Labrador Retriever (LR), Leonberger (LEO), and Irish Wolfhound (IW) followed from birth until age 9 yrs. We wanted to investigate whether radiological hip dysplasia status given at approximately age 12-18 mos and other factors during growth influenced development of clinical signs due to hip-joint disease necessitating veterinary consultation. Whether or not such signs occurred due to hip dysplasia or due to secondary or primary DJD could not be distinguished, and we therefore used the term "owner-reported veterinary diagnosed hip-related clinical signs" ("the event"). The included dogs were followed from birth to the event or until a maximum of 9 yrs of age. Our objectives were to describe breed differences in time to incidence and to evaluate potential risk factors for the time to event. We used Kaplan-Meier curves to describe time to incidence, and potential risk factors were assessed by use of a Cox proportional-hazards model. We enrolled 494 dogs from 103 litters, and 46 dogs were reported as having had the event during the observation period. We observed a significant time-varying effect (TVE): LR and LEO developed clinical signs later in life than NF. If the radiological hip status was either mild, moderate, or severe the hazard of experiencing the event was significantly increased. Access to off-leash exercise at age 12 mos decreased the hazard of the event, and the hazard varied by litter. The findings supported the hypothesis that radiological hip status at screening and exercise conditions during growth influenced the time to incidence of the event and that there were breed differences in time to the event. PMID- 21982690 TI - Self-organizing ARTMAP rule discovery. AB - The self-organizing ARTMAP rule discovery (SOARD) system derives relationships among recognition classes during online learning. SOARD training on input/output pairs produces the basic competence of direct recognition of individual class labels for new test inputs. As a typical supervised system, it learns many-to-one maps, which recognize different inputs (Spot, Rex) as belonging to one class (dog). As an ARTMAP system, it also learns one-to-many maps, allowing a given input (Spot) to learn a new class (animal) without forgetting its previously learned output (dog), even as it corrects erroneous predictions (cat). As it learns individual input/output class predictions, SOARD employs distributed code representations that support online rule discovery. When the input Spot activates the classes dogand animal, confidence in the rule dog->animal begins to grow. When other inputs simultaneously activate classes cat and animal, confidence in the converse rule, animal->dog, decreases. Confidence in a self-organized rule is encoded as the weight in a path from one class node to the other. An experience based mechanism modulates the rate of rule learning, to keep inaccurate predictions from creating false rules during early learning. Rules may be excitatory or inhibitory so that rule-based activation can add missing classes and remove incorrect ones. SOARD rule activation also enables inputs to learn to make direct predictions of output classes that they have never experienced during supervised training. When input Rex activates its learned class dog, the rule dog >animal indirectly activates the output class animal. The newly activated class serves as a teaching signal which allows input Rex to learn direct activation of the output class animal. Simulations using small-scale and large-scale datasets demonstrate functional properties of the SOARD system in both spatial and time series domains. PMID- 21982691 TI - Single-cannula technique for operative arthroscopy using holmium:YAG laser. PMID- 21982692 TI - Three-dimensional reconstruction of maxillae using spiral computed tomography and its application in postoperative adult patients with unilateral complete cleft lip and palate. AB - PURPOSE: To establish a method to analyze malformed maxillae of postoperative adult patients with unilateral complete cleft lip and palate in 3 dimensions. MATERIALS AND METHODS: A total of 35 landmarks were defined and used to reconstruct 3-dimensional maxillary images of healthy Chinese Han subjects and 30 postoperative Chinese Han adult patients (17 men and 13 women, with mean age of 19.07 years) with unilateral complete cleft lip and palate. This was done using spiral computed tomography, and their corresponding parameters were analyzed using SimPlant software, version 11.04, and compared by t test using SAS software, version 6.12. RESULTS: Of the 7 centered landmarks, A and ANS in the patients were obviously deviated to the nonoperative side (P < .01) and the symmetrical landmark pairs INM'-INM, SNM'-SNM and SPr'-SPr, but not MA'-MA, SoF' SoF, and LPAC-LPA in the infraorbital region and piriform aperture peritreme in healthy subjects were shifted toward the coordinate sagittal plane S. The data also showed that the maxillae in the patients' operative side were hypoplastic, especially in the posteroanterior direction compared with the nonoperative side and healthy subjects. CONCLUSIONS: The proposed method can precisely measure the distances of the maxillary landmarks to 3-dimensional coordinates and has application potential in evaluating maxillary deformity in patients with postoperative unilateral complete cleft lip and palate. PMID- 21982693 TI - Post-traumatic implant-supported restoration of the anterior maxillary teeth using cancellous bone block allografts. AB - PURPOSE: To prospectively evaluate the outcome of dental implants placed in the post-traumatic anterior maxilla after ridge augmentation with cancellous freeze dried block bone allografts. MATERIALS AND METHODS: Patients presenting with a history of anterior dentoalveolar trauma with bony deficiencies in the sagittal (>=3 mm) and vertical (<3 mm) planes according to computed tomography were included. The recipient sites were reconstructed with cancellous bone block allografts. After 6 months of healing, implants were placed. The primary outcomes of interest were 1) bone measurements taken before grafting, at the time of implant placement, and at stage 2 operations; 2) implant survival; and 3) complications. RESULTS: The sample was composed of 20 consecutive patients with a mean age of 25 +/- 7 years. We used 28 cancellous allogeneic bone blocks, and 31 implants were inserted. Of the 31 implants, 12 were immediately restored. The mean follow-up was 42 +/- 15 months. Graft and implant survival rates were 92.8% and 96.8%, respectively. Mean bone gain in the sagittal and vertical planes was 5 +/- 0.5 mm horizontally and 2 +/- 0.5 mm (P < .001). Successful restoration was achieved in all patients with fixed implant-supported prostheses. Soft tissue complications occurred in 7 patients (35%). Complications after cementation of the crowns were seen in 3 implants (9.6%). All implants remained clinically osseointegrated at the end of the follow-up examination. There was no crestal bone loss around the implants beyond the first implant thread. CONCLUSION: Cancellous block allograft can be used successfully for post-traumatic implant supported restoration in the anterior maxilla. PMID- 21982694 TI - Change in bite force and electromyographic activity of masticatory muscle in accordance with change of occlusal plane. AB - PURPOSE: The purpose of the present study was to evaluate effects of occlusal plane on masticatory function (biting force, masticatory muscle activity, biting efficiency) after bimaxillary orthognathic surgery. PATIENTS AND METHODS: The subjects of the present study consisted of a group of 55 adults who had undergone bimaxillary surgery more than 6 months earlier. Lateral cephalographs, bite force, and electromyographic measurements of the anterior temporal [EMG(t)] and masseter muscles [EMG(m)] were recorded before and after bimaxillary surgery. Statistical analyses were performed. RESULTS: In the increased occlusal plane group, the frequency of decreased EMG(t) was significantly high. The frequency of increased EMG(t) was also significantly high in the decreased occlusal plane group. A negative correlation was found between the postoperative occlusal plane angle and the biting force efficiency change. No significant difference was found between the group that moved from an abnormal to a normal range and the group that moved from a normal to an abnormal range. The occlusal plane change was significantly greater in the decreased EMG(t) group than in the increased EMG(t) group. CONCLUSIONS: The value of EMG(t) was related to the changes in the occlusal plane, and the biting efficiency was affected by the postoperative occlusal plane angle. However, normalization of the occlusal plane might not play a major role in masticatory function. PMID- 21982695 TI - Cryptococcal immune reconstitution syndrome in HIV-negative patients. PMID- 21982696 TI - The neural correlates of object-centered processing in reading: a lesion study of neglect dyslexia. AB - Neglect dyslexia--a peripheral reading disorder generally associated with left spatial neglect--is characterized by omissions or substitutions of the initial letters of words. Several observations suggest that neglect dyslexia errors are independent of viewer-centered coordinates; the disorder is therefore thought to reflect impairment at the level of object-centered representations. This hypothesis is indirectly supported by lesion studies connecting object-centered neglect errors with damage to posterior cortical regions lying in the ventral visual stream. Here, we performed a lesion-symptom mapping study of 40 patients with spatial neglect asked to read words presented at different positions relative to a viewer-centered coordinate frame. We found that the frequency of object-centered reading errors was constant across horizontal positions, whereas the frequency of entirely neglected words (reflecting a page-centered deficit) linearly increased from right to left. Damage to the intraparietal sulcus and the angular and middle temporal gyri was the best predictor of object-centered errors. We discuss these findings with reference to a role of the posterior parietal lobe in adapting the size of the attentional focus and biasing object representations elaborated in the ventral visual stream. PMID- 21982697 TI - Problem gamblers exhibit reward hypersensitivity in medial frontal cortex during gambling. AB - Problem gambling (PG) is increasingly conceptualized as an addiction akin to substance abuse, rather than an impulse control disorder, however the mechanism of addiction remains unclear. Neuroimaging investigations have supported a "reward deficiency" hypothesis for PG by suggesting a blunted response to gambling, particularly in the striatum. Here we describe electrophysiological evidence of a hypersensitive response to gambling feedback in problem gamblers. Previous research in healthy participants has shown that feedback during gambling tasks triggers stereotypical neural responses including the Feedback-Related Mediofrontal Negativity (FRN), the feedback-related P300, and an increase in induced theta-band (4-8 Hz) power. We tested the theory that abnormal feedback processing characterizes brain activity in problem gamblers while gambling. EEG was recorded from non-gamblers and self-identified gamblers as they engaged in a computerized version of the Iowa Gambling Task. Feedback about valence (win vs. loss) triggered a FRN in both groups, but in gamblers this was preceded by an early-latency hypersensitive fronto-central difference to feedback. This early FRN was correlated with gambling severity and was localized to medial frontal cortex using distributed source imaging (CLARA). Gamblers also differed in responses to risk, showing a blunted P300 component and less EEG power in the theta band. Here we suggest that a more nuanced interpretation of reward deficiency is called for with respect to PG. For certain aspects of brain function, gamblers may exhibit hypersensitivity to reward feedback more akin to drug sensitization than reward deficiency. Our results also suggest that the neurologically normal brain employs dissociable systems in the processing of feedback from tasks involving risky decision making. PMID- 21982698 TI - Structural correlates of prospective memory. AB - Prospective memory (PM) includes the encoding and maintenance of an intention, and the retrieval and execution of this intention at the proper moment in the future. The present study expands upon previous behavioral, electrophysiological, and functional work by examining the association between grey matter volume and PM. Estimates of grey matter volume in theoretically relevant regions of interest (prefrontal, parietal, and medial temporal) were obtained in conjunction with performance on two PM tasks in a sample of 39 cognitively normal and very mildly demented older adults. The first PM task, termed focal in the literature, is supported by spontaneous retrieval of the PM intention whereas the second, termed non-focal, relies on strategic monitoring processes for successful intention retrieval. A positive relationship was observed between medial temporal volume and accuracy on the focal PM task. An examination of medial temporal lobe subregions revealed that this relationship was strongest for the hippocampus, which is considered to support spontaneous memory retrieval. There were no significant structure-behavior associations for the non-focal PM task. These novel results confirm a relationship between behavior and underlying brain structure proposed by the multiprocess theory of PM, and extend findings on cognitive correlates of medial temporal lobe integrity. PMID- 21982699 TI - Modified step-cut osteotomy for post-traumatic cubitus varus: our experience with 14 children. AB - BACKGROUND: Lateral closing wedge osteotomy is a commonly described procedure for correcting cosmetically unacceptable post-traumatic cubitus varus deformity in children. However, complications like residual deformity, lateral prominence, loss of fixation and ulnar nerve palsies commonly contribute to poor outcomes with such an osteotomy. PATIENTS AND METHODS: Fourteen children (11 boys and three girls) presenting a mal-united extension type supracondylar fracture of the humerus with an average age of 9.07 years (6-14 years) were operated around 3.6 years (1.5-7 years) after the injury using a modified step-cut osteotomy. The average follow-up period was 2.1 years (1-4 years). Objective assessment included measurement of preoperative and postoperative lateral prominence index, carrying angle and range of elbow motion. Results were graded excellent, good or poor as per the Oppenheim criteria. RESULTS: There were eight excellent, five good and one poor result. A residual varus of more than 10 degrees was seen in the single patient with poor result. None of the patients showed a prominent lateral humeral condyle or formation of hypertrophic scar. Our results were comparable to the published results of the classical lateral closing wedge osteotomy in terms of elbow motion and correction of deformity. CONCLUSION: A modified step-cut osteotomy is a safe and simple procedure which prevents lateral prominence and leads to good or excellent outcomes in most of the patients. The step-cut osteotomy procedure, mentioned here, might be beneficial over the conventional lateral closing wedge osteotomy in certain aspects like the lateral humeral condyle prominence, scar acceptibility and cosmesis. However, the apparent aforementioned advantages of this osteotomy over the conventional lateral closing wedge osteotomy needs to be further evaluated and confirmed on the basis of large, prospective randomised controlled trials. PMID- 21982700 TI - Telemedicine in heart failure: pre-specified and exploratory subgroup analyses from the TIM-HF trial. AB - BACKGROUND: Meta-analyses have suggested that remote telemedical management (RTM) positively affects clinical outcomes in chronic HF patients. The results of two recent randomised RTM trials do not corroborate these results. We aim to report prospectively defined and exploratory subgroup analyses for the TIM-HF trial and to identify a patient profile that could potentially benefit from RTM for further investigation in randomised clinical trials. METHODS: In TIM-HF, 710 stable chronic HF patients, in NYHA class II or III with a history of HF decompensation within 2 years previously or a LVEF <= 25% were randomly assigned (1:1) to RTM or usual care. The primary outcome was total death and secondary outcomes included days lost due to death or HF hospitalisation and a composite of cardiovascular death and HF hospitalisation. Twelve subgroups were prospectively defined and patient profiling was investigated for the subgroup with a prior history of HF decompensation, an LVEF >= 25% and a PHQ-9 score<10. RESULTS: The subgroup treatment effects were significant for total mortality for the PHQ-9 subgroup only (p for interaction<0.027). For the outcome 'number of days lost due to hospitalisation for HF or death', the subgroup treatment effects were significant (p for interaction<0.05) for patients with a prior HF decompensation or an ICD implant or a PHQ score of <10 and for the patient-profiling subgroup. CONCLUSIONS: Telemedicine management may not be appropriate for all HF patients. Future research needs to investigate which HF population may benefit from this intervention. PMID- 21982701 TI - Estrogens and obesity: is it all in our heads? AB - Estrogens have preventative effects on weight gain and associated comorbidities, but the tissue-specific targets remain unknown. Here, Xu et al. (2011) demonstrate that ablation of estrogen signaling in two populations of hypothalamic neurons leads to weight gain and subsequent metabolic dysregulation and could be important target sites of estrogen actions. PMID- 21982702 TI - DisseCCTing phospholipid function in lipid droplet dynamics. AB - Phospholipids provide an amphipathic barrier between lipid droplets and the cytoplasm of cells. In this issue of Cell Metabolism, Krahmer and colleagues (2011) define a role for phosphatidylcholine in preventing lipid droplet coalescence and show that the rate-limiting enzyme in phosphatidylcholine synthesis is activated through binding to lipid droplets. PMID- 21982703 TI - Of fat, beta cells, and diabetes. AB - The molecular mechanisms linking diet, obesity, and type 2 diabetes are still poorly understood. In a recent paper, Ohtsubo et al. (2011) show that high lipid levels induce nuclear exclusion of Foxa2 and HNF1alpha in beta cells, leading to impaired expression and glycosylation of proteins controlling glucose-stimulated insulin secretion. PMID- 21982704 TI - Orexin turns up the heat on obesity. AB - Brown adipocytes burn chemical energy to produce heat for protection against hypothermia and obesity. Sellayah et al. now reveal that a secreted neuropeptide, Orexin, functions a key driver of brown adipocyte differentiation through direct actions on brown adipose precursors. PMID- 21982705 TI - Metabolic flux and the regulation of mammalian cell growth. AB - The study of normal mammalian cell growth and the defects that contribute to disease pathogenesis links metabolism to cell growth. Here, we visit several aspects of growth-promoting metabolism, emphasizing recent advances in our understanding of how alterations in glucose metabolism affect cytosolic and mitochondrial redox potential and ATP generation. These alterations drive cell proliferation not only through supporting biosynthesis, energy metabolism, and maintaining redox potential but also through initiating signaling mechanisms that are still poorly characterized. The evolutionary basis of these additional layers of growth control is also discussed. PMID- 21982706 TI - Distinct hypothalamic neurons mediate estrogenic effects on energy homeostasis and reproduction. AB - Estrogens regulate body weight and reproduction primarily through actions on estrogen receptor-alpha (ERalpha). However, ERalpha-expressing cells mediating these effects are not identified. We demonstrate that brain-specific deletion of ERalpha in female mice causes abdominal obesity stemming from both hyperphagia and hypometabolism. Hypometabolism and abdominal obesity, but not hyperphagia, are recapitulated in female mice lacking ERalpha in hypothalamic steroidogenic factor-1 (SF1) neurons. In contrast, deletion of ERalpha in hypothalamic pro opiomelanocortin (POMC) neurons leads to hyperphagia, without directly influencing energy expenditure or fat distribution. Further, simultaneous deletion of ERalpha from both SF1 and POMC neurons causes hypometabolism, hyperphagia, and increased visceral adiposity. Additionally, female mice lacking ERalpha in SF1 neurons develop anovulation and infertility, while POMC-specific deletion of ERalpha inhibits negative feedback regulation of estrogens and impairs fertility in females. These results indicate that estrogens act on distinct hypothalamic ERalpha neurons to regulate different aspects of energy homeostasis and reproduction. PMID- 21982707 TI - Inositol polyphosphate 4-phosphatase B as a regulator of bone mass in mice and humans. AB - Osteoporosis is a multifactorial genetic disease characterized by reduction of bone mass due to dysregulation of osteoclast differentiation or maturation. Herein, we identified a regulator of osteoclastogenesis, the murine homolog of inositol polyphosphate 4-phosphatase type IIalpha (Inpp4balpha). Expression of Inpp4balpha is detected from early osteoclast differentiation to activation stage. Targeted expression of native Inpp4balpha ex vivo repressed whereas phosphatase-inactive Inpp4balpha stimulated osteoclast differentiation. Inpp4balpha acts on intracellular calcium level that modulates NFATc1 nuclear translocation and activation. In vivo mice deficient in Inpp4b displayed increased osteoclast differentiation rate and potential resulting in decreased bone mass and osteoporosis. Importantly, INPP4B in human was identified as a susceptibility locus for osteoporosis. This study defined Inpp4b as a major modulator of the osteoclast differentiation and as a gene linked to variability of bone mineral density in mice and humans. PMID- 21982708 TI - Orexin is required for brown adipose tissue development, differentiation, and function. AB - Orexin (OX) neuropeptides stimulate feeding and arousal. Deficiency of orexin is implicated in narcolepsy, a disease associated with obesity, paradoxically in the face of reduced food intake. Here, we show that obesity in orexin-null mice is associated with impaired brown adipose tissue (BAT) thermogenesis. Failure of thermogenesis in OX-null mice is due to inability of brown preadipocytes to differentiate. The differentiation defect in OX-null neonates is circumvented by OX injections to OX-null dams. In vitro, OX, triggers the full differentiation program in mesenchymal progenitor stem cells, embryonic fibroblasts and brown preadipocytes via p38 mitogen activated protein (MAP) kinase and bone morphogenetic protein receptor-1a (BMPR1A)-dependent Smad1/5 signaling. Our study suggests that obesity associated with OX depletion is linked to brown-fat hypoactivity, which leads to dampening of energy expenditure. Thus, orexin plays an integral role in adaptive thermogenesis and body weight regulation via effects on BAT differentiation and function. PMID- 21982709 TI - The differential role of Hif1beta/Arnt and the hypoxic response in adipose function, fibrosis, and inflammation. AB - In obesity, adipocytes distant from vasculature become hypoxic and dysfunctional. This hypoxic response is mediated by hypoxia-inducible factors (Hif1alpha, Hif2alpha, and Hif3alpha) and their obligate partner, Hif1beta (Arnt). We show that mice lacking Hif1beta in fat (FH1betaKO) are lean, exhibit reduced adipocyte size, and are protected from age- and diet-induced glucose intolerance. There is also reduced Vegf and vascular permeability in FH1betaKO fat, but diet-induced inflammation and fibrosis is unchanged. Adipocytes from FH1betaKO mice have reduced glucose uptake due to decreased Glut1 and Glut4, which is mirrored in 3T3 L1 adipocytes with Hif1beta knockdown. Hif1beta knockdown cells also fail to respond appropriately to hypoxia with reduced cellular respiration and reduced mitochondrial gene expression. Some, but not all, of these effects are reproduced by Hif1alpha knockdown. Thus, Hif1beta/Arnt regulates glucose uptake, mitochondrial gene expression, and vascular permeability to control adipose mass and function, providing a target for obesity therapy. PMID- 21982710 TI - Phosphatidylcholine synthesis for lipid droplet expansion is mediated by localized activation of CTP:phosphocholine cytidylyltransferase. AB - Lipid droplets (LDs) are cellular storage organelles for neutral lipids that vary in size and abundance according to cellular needs. Physiological conditions that promote lipid storage rapidly and markedly increase LD volume and surface. How the need for surface phospholipids is sensed and balanced during this process is unknown. Here, we show that phosphatidylcholine (PC) acts as a surfactant to prevent LD coalescence, which otherwise yields large, lipolysis-resistant LDs and triglyceride (TG) accumulation. The need for additional PC to coat the enlarging surface during LD expansion is provided by the Kennedy pathway, which is activated by reversible targeting of the rate-limiting enzyme, CTP:phosphocholine cytidylyltransferase (CCT), to growing LD surfaces. The requirement, targeting, and activation of CCT to growing LDs were similar in cells of Drosophila and mice. Our results reveal a mechanism to maintain PC homeostasis at the expanding LD monolayer through targeted activation of a key PC synthesis enzyme. PMID- 21982712 TI - Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. AB - Type 2 diabetes (T2D) has become epidemic in our modern lifestyle, likely due to calorie-rich diets overwhelming our adaptive metabolic pathways. One such pathway is mediated by nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in mammalian NAD(+) biosynthesis, and the NAD(+)-dependent protein deacetylase SIRT1. Here, we show that NAMPT-mediated NAD(+) biosynthesis is severely compromised in metabolic organs by high-fat diet (HFD). Strikingly, nicotinamide mononucleotide (NMN), a product of the NAMPT reaction and a key NAD(+) intermediate, ameliorates glucose intolerance by restoring NAD(+) levels in HFD-induced T2D mice. NMN also enhances hepatic insulin sensitivity and restores gene expression related to oxidative stress, inflammatory response, and circadian rhythm, partly through SIRT1 activation. Furthermore, NAD(+) and NAMPT levels show significant decreases in multiple organs during aging, and NMN improves glucose intolerance and lipid profiles in age-induced T2D mice. These findings provide critical insights into a potential nutriceutical intervention against diet- and age-induced T2D. PMID- 21982711 TI - Postprandial hepatic lipid metabolism requires signaling through Akt2 independent of the transcription factors FoxA2, FoxO1, and SREBP1c. AB - Under conditions of obesity and insulin resistance, the serine/threonine protein kinase Akt/PKB is required for lipid accumulation in liver. Two forkhead transcription factors, FoxA2 and FoxO1, have been suggested to function downstream of and to be negatively regulated by Akt and are proposed as key determinants of hepatic triglyceride content. In this study, we utilize genetic loss of function experiments to show that constitutive activation of neither FoxA2 nor FoxO1 can account for the protection from steatosis afforded by deletion of Akt2 in liver. Rather, another downstream target positively regulated by Akt, the mTORC1 complex, is required in vivo for de novo lipogenesis and Srebp1c expression. Nonetheless, activation of mTORC1 and SREBP1c is not sufficient to drive postprandial lipogenesis in the absence of Akt2. These data show that insulin signaling through Akt2 promotes anabolic lipid metabolism independent of Foxa2 or FoxO1 and through pathways additional to the mTORC1 dependent activation of SREBP1c. PMID- 21982713 TI - Mitochondrial complex III ROS regulate adipocyte differentiation. AB - Adipocyte differentiation is characterized by an increase in mitochondrial metabolism. However, it is not known whether the increase in mitochondrial metabolism is essential for differentiation or a byproduct of the differentiation process. Here, we report that primary human mesenchymal stem cells undergoing differentiation into adipocytes display an early increase in mitochondrial metabolism, biogenesis, and reactive oxygen species (ROS) generation. This early increase in mitochondrial metabolism and ROS generation was dependent on mTORC1 signaling. Mitochondrial-targeted antioxidants inhibited adipocyte differentiation, which was rescued by the addition of exogenous hydrogen peroxide. Genetic manipulation of mitochondrial complex III revealed that ROS generated from this complex is required to initiate adipocyte differentiation. These results indicate that mitochondrial metabolism and ROS generation are not simply a consequence of differentiation but are a causal factor in promoting adipocyte differentiation. PMID- 21982714 TI - Imaging cytosolic NADH-NAD(+) redox state with a genetically encoded fluorescent biosensor. AB - NADH is a key metabolic cofactor whose sensitive and specific detection in the cytosol of live cells has been difficult. We constructed a fluorescent biosensor of the cytosolic NADH-NAD(+) redox state by combining a circularly permuted GFP T Sapphire with a bacterial NADH-binding protein, Rex. Although the initial construct reported [NADH] * [H(+)] / [NAD(+)], its pH sensitivity was eliminated by mutagenesis. The engineered biosensor Peredox reports cytosolic NADH:NAD(+) ratios and can be calibrated with exogenous lactate and pyruvate. We demonstrated its utility in several cultured and primary cell types. We found that glycolysis opposed the lactate dehydrogenase equilibrium to produce a reduced cytosolic NADH NAD(+) redox state. We also observed different redox states in primary mouse astrocytes and neurons, consistent with hypothesized metabolic differences. Furthermore, using high-content image analysis, we monitored NADH responses to PI3K pathway inhibition in hundreds of live cells. As an NADH reporter, Peredox should enable better understanding of bioenergetics. PMID- 21982716 TI - Comparison of Mandarin tone and speech perception between advanced combination encoder and continuous interleaved sampling speech-processing strategies in children. AB - OBJECTIVE: This study was performed to compare cochlear implant (CI) users' performance in Mandarin speech and tone perception between 2 types of speech processing strategies-advanced combination encoder (ACE) and continuous interleaved sampling (CIS)-under quiet and noisy conditions. METHODS: This study involved 10 congenitally deaf children (age range, 5.7-15.3 years; mean, 9.2 years) who received the Nucleus 24-channel CI system cochlear device (CI24R; Cochlear Ltd, Lane Cove NSW, Australia). The subjects used ACE since switching on their CI devices. Speech and tone perception tests were administered under quiet and noisy (+5 dB signal-to-noise ratio) conditions with ACE and CIS strategies 20 minutes and 2 weeks apart. RESULTS: Regardless of the strategy used, subjects showed significantly higher scores in speech perception than in tone recognition. Under noisy conditions, subjects had significantly higher tone identification scores with the CIS than the ACE strategy (P = .038). There was no significant difference in speech identification score between the strategies. Subjects showed significant higher tone identification and speech perception scores under quiet than noisy (+5 dB signal-to-noise ratio) conditions. Subjectively, 6 subjects preferred the ACE strategy, and the remaining 4 preferred the CIS strategy. The strategy preference of the subjects was related to speech perception performance rather than tone identification. A significant correlation was observed between tone identification and speech recognition, regardless of whether speech was evaluated by consonants (r = 0.669, P < .001), vowels (r = 0.426, P = .001), or sentences (r = 0.294, P = .023). CONCLUSION: There are only 4 patterns of tone in Mandarin, which is far fewer than the number of speech sounds. However, tone identification is poorer than speech perception. The CIS speech-processing strategy may improve tone identification under noisy conditions. Before improved speech strategies to code acoustic characteristics of tone can be developed, it would be worthwhile to try both CIS and ACE for CI users and to select the most suitable speech-processing strategy according to the subjective preference and objective performance. PMID- 21982715 TI - Genetically encoded fluorescent sensors for intracellular NADH detection. AB - We have developed genetically encoded fluorescent sensors for reduced nicotinamide adenine dinucleotide (NADH), which manifest a large change in fluorescence upon NADH binding. We demonstrate the utility of these sensors in mammalian cells by monitoring the dynamic changes in NADH levels in subcellular organelles as affected by NADH transport, glucose metabolism, electron transport chain function, and redox environment, and we demonstrate the temporal separation of changes in mitochondrial and cytosolic NADH levels with perturbation. These results support the view that cytosolic NADH is sensitive to environmental changes, while mitochondria have a strong tendency to maintain physiological NADH homeostasis. These sensors provide a very good alternative to existing techniques that measure endogenous fluorescence of intracellular NAD(P)H and, owing to their superior sensitivity and specificity, allow for the selective monitoring of total cellular and compartmental responses of this essential cofactor. PMID- 21982717 TI - Screening for hypogonadism in diabetes 2008/9: results from the Cheshire Primary Care cohort. AB - AIM: There is increasing awareness of hypogonadism in men with type 2 diabetes but limited data from Primary Care. SUBJECTS AND METHODS: The anonymised records of 6457 male patients aged 18-80 years with diabetes were accessed. Within the last 2 years 391 men (6.0% of total) underwent measurement of serum testosterone. Data search was performed through the centralised data facility afforded by EMIS(r), the majority GP systems provider in Cheshire. RESULTS: 4.4% of type 2 diabetes men screened were frankly hypogonadal with a serum total testosterone of less than 8.0 nmol/l. For borderline hypogonadism (serum total testosterone 8 11.99 nmol/l) the proportion of type 2 diabetes men rose to 32.1%. Age adjusted mean (geometric) testosterone was lower in men with type 2 diabetes (13.6 nmol/l 95%CI: 13.1-14.2) vs type 1 diabetes (17.9 nmol/l; 95%CI 15.2-21.0), F=10.3; p=0.0014. For those screened age adjusted body mass index (BMI) was greater in type 2 diabetes at 30.7 (30.1-31.3) vs 28.4 (26.1-30.6)kg/m(2) in type 1 diabetes (F=4.3; p=0.04). Multiple linear regression analysis indicated that there was a statistically significant interaction (P=0.014) between BMI and diabetes type in their relation with log testosterone. For persons with type 1 DM and type 2 DM, testosterone can be expected to decrease by 6% (P=0.002) and by 1% (P=0.002) respectively, for every one unit increment in BMI. CONCLUSIONS: There is manifestly a subset of men with diabetes and androgen deficiency who could benefit from testosterone replacement. BMI has an independent influence on androgen status. PMID- 21982718 TI - Pentacycloundecane derived hydroxy acid peptides: a new class of irreversible non scissile ether bridged type isoster as potential HIV-1 wild type C-SA protease inhibitors. AB - Novel peptides incorporating the PCU derived hydroxy acid (5-hydroxy-4 oxahexacyclo[5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)]dodecane) were synthesized and their activity against the resistance-prone wild type C-South African (C-SA) HIV protease is reported. The attachment of peptides and peptoids to the PCU derived hydroxy acid resulted in a series of structurally diverse promising HIV-1 protease inhibitors. Amongst the nine novel compounds, 16, 17, 20 and 23 gave IC(50) values ranging from 0.6 to 5.0 MUM against the wild type C-SA HIV-1 protease enzyme. Docking studies and molecular dynamic (MD) simulations have been carried out in order to understand the binding mode of the PCU moiety at the active site of the HIV protease enzyme. A conserved hydrogen bonding pattern between the PCU derived hydroxy ether and the active site residues, ASP25/ASP25', was observed in all active compounds. PMID- 21982719 TI - Monitoring drug safety with registries: useful components of postmarketing pharmacovigilance systems. AB - OBJECTIVE: At the time of licensing by regulatory agencies, the full range of risks and possible adverse drug reactions associated with a medication is rarely fully realized. This commentary aims to describe the role of registries as useful components of postmarketing pharmacovigilance systems for monitoring highly specialized medications associated with significant financial costs. STUDY DESIGN AND SETTING: We consider the limitations of traditional pharmacovigilance programs and discuss the strengths, limitations, and uses of registries in postmarketing pharmacovigilance systems. RESULTS: Registries have become increasingly appealing in postmarketing surveillance of medications; however, their exact role continues to evolve. Key registry projects, including the Prospective Immunogenicity Surveillance Registry, British Society for Rheumatology Biologics Register, Australian Rheumatology Association Database, the Haemostasis Registry, and the Bosentan Patient Registry highlight the value of registries for monitoring the incidence of rare adverse events. CONCLUSION: Although often limited by lack of a control group and the need for complete case ascertainment to maintain data integrity, registries are a useful component of postmarketing pharmacovigilance systems for monitoring highly specialized medications associated with significant financial costs. PMID- 21982720 TI - Endothelial vascular toxicity from chemotherapeutic agents: preclinical evidence and clinical implications. AB - In cancer biology angiogenesis plays a vital role in tumour growth and its subsequent metastatic potential. By targeting the angiogenic process, a new treatment strategy was added in the clinician's therapeutic armamentarium. On the other hand, numerous classic cytotoxic agents are currently considered as potential angiogenesis inhibitors, although they were not originally developed as such, representing the so-called "accidental" anti-angiogenic drugs. The discovery of these new properties of classic cytotoxic agents led to the re evaluation of their effect on vascular cells, rendering thus the endothelium an appealing target for therapeutic intervention, either with chemotherapy alone or with combination of cytotoxics with molecular angiogenesis inhibitors. Moreover, current evidence supports that chemotherapy-induced endothelial dysfunction constitutes an integrating predictive marker of future cardiovascular events and correlates well with traditional cardiovascular risk factors. It has therefore been suggested that evaluation of endothelial function may be useful in identifying asymptomatic subjects at high risk for cardiovascular events as well as for risk stratification of patients with established cardiovascular disease. Integration of the assessment of endothelial function in the clinical setting will thus enable effective intervention strategies to prevent or minimize the impact of these late adverse effects and design accurate follow-up protocols focused on cardiovascular complications. In the current review we provide a comprehensive overview of the effects of cytotoxic chemotherapeutic agents on endothelial function and the clinical implications of chemotherapy-associated endothelial toxicity in patients with cancer. PMID- 21982721 TI - The psychometric properties of the dot-probe paradigm when used in pain-related attentional bias research. AB - In recent years, there has been increasing acknowledgment of the need for psychometric data regarding the dot-probe paradigm. The aim of the present study was to provide some data on the psychometric properties of the dot-probe paradigm in the context of pain-related research. Using the data of a large pain-free sample and a large chronic pain sample, the present study examined the psychometric properties of a picture- and word-based dot-probe task. It also examined the data of idiosyncratically selected stimuli designed to be relevant to each participant and compared this with the data of neutral stimuli and nonsalient pain-related stimuli. Poor levels of internal consistency (alpha range: -.44 to .28; split-half r range: -.35 to .11) and test-retest reliability (r range: -.14 to .13) were found among the pain-free sample, irrespective of the task used or the stimuli used. There was limited evidence of comparability between the 2 tasks among the chronic pain sample (r range: -.08 to .26) and similarly poor levels of internal-consistency (alpha range: -.56 to .17; split half r range: -.20 to .25). The findings of the present study therefore suggest that psychometric issues may be important to pain-related attentional bias research. More research is, however, undoubtedly needed. PERSPECTIVE: The aim of the present study was to provide data regarding the psychometric properties of the dot-probe paradigm within the specific context of pain-related attentional bias research. The findings of this study suggest that psychometric issues may be an important consideration in pain-related attentional biases research. PMID- 21982722 TI - Microbial enhancement of crop resource use efficiency. AB - Naturally occurring soil microbes may be used as inoculants to maintain crop yields despite decreased resource (water and nutrient) inputs. Plant symbiotic relationships with mycorrhizal fungi alter root aquaporin gene expression and greatly increase the surface area over which plant root systems take up water and nutrients. Soil bacteria on the root surface alter root phytohormone status thereby increasing growth, and can make nutrients more available to the plant. Combining different classes of soil organism within one inoculant can potentially take advantage of multiple plant growth-promoting mechanisms, but biological interactions between inoculant constituents and the plant are difficult to predict. Whether the yield benefits of such inocula allow modified nutrient and water management continues to challenge crop biotechnologists. PMID- 21982723 TI - Pharmacokinetics of three doses of sublingual testosterone in healthy premenopausal women. AB - CONTEXT: Sublingual testosterone is a single-dose treatment often used in studies regarding social, cognitive and sexual behavior. It is hypothesized that an increase in the ratio of free to total testosterone (free fraction) is indirectly, via genomic effects, responsible for the behavioral effects after sublingual testosterone administration. OBJECTIVE: To characterize the pharmacokinetics of three doses sublingual testosterone in premenopausal women. Also, to investigate the SHBG saturation threshold influencing the free level and free fraction of testosterone. DESIGN: We conducted an investigator-blind, randomized, cross-over placebo controlled study. SETTING: This study was undertaken at the research and development department of a scientific company for research regarding female sexual dysfunction. PARTICIPANTS: 16 healthy premenopausal women (mean age 27.3+/-5.3 years). INTERVENTIONS: Sublingual testosterone solution; 0.25, 0.50 and 0.75 mg. MAIN OUTCOMES MEASURE: The pharmacokinetics of three single doses sublingual testosterone solution; the influence of SHBG levels on free and total levels of testosterone. RESULTS: After sublingual testosterone administration, serum free and total testosterone levels peaked at 15 min and reached baseline levels within 150 min. The AUCs and C(max) of free and total testosterone differed significantly between the three doses (p<0.0001) and increased dose-dependently. A dose-dependent increase in free fraction of testosterone was found in women with low SHBG levels, but not in women with high SHBG levels. CONCLUSIONS: The three doses sublingual testosterone are rapidly absorbed and quickly metabolized in premenopausal women. These data demonstrate the influence of SHBG levels on the treatment induced alterations in plasma free testosterone. PMID- 21982724 TI - Bradykinin promotes TLR2 expression in human gingival fibroblasts. AB - Bradykinin (BK) is implicated in the sensation of pain, vasodilation, increases in vascular permeability and pathogenic processes associated with inflammation. Studies have shown that BK promotes the intracellular movement of calcium in human gingival fibroblasts by binding to the B2 receptor. In this study we investigated the effect of BK on regulation of Toll-like receptor 2 (TLR2) expression. Our results show that BK stimulates TLR2 receptor transcription and translation by activation of protein kinase C as well as AKT. Our study contributes important information on the regulation and expression of molecules that promote chronic inflammatory processes, which lead to periodontitis and consequently to loss of the dental organ. PMID- 21982725 TI - Senescence and pre-malignancy: how do tumors progress? AB - Cellular senescence is a tumor suppressor response that has been observed both in vitro and in vivo, and features of senescence have been documented in various human premalignant lesions, including melanoma, colon and lung adenoma, prostatic intraepithelial neoplasia, and others. The fact that a subset of these lesions eventually progress to malignant invasive tumors suggests that premalignant cells can either bypass or escape the senescent response. Much work has been done to understand the mechanisms underlying such progression, but it remains unclear whether tumors progress by evasion of senescence induction, or by disruption of senescence maintenance, or whether both mechanisms can occur in human cancer development. This review presents the current evidence for mechanisms of senescence evasion and reversion, and discusses what has been learnt about this process using in vitro and in vivo experimental systems. As we learn more about the key signaling effectors of senescence, the hope is that appropriate targets will be identified for preservation and/or re-induction of senescence in human tumors. Such knowledge may also find application in better estimation of risks of cancer progression in individual premalignant lesions, which will lead to more accurate allocation of appropriate treatment options for such patients. PMID- 21982726 TI - Ovarian hyperandrogenism in adolescents and young women with type I diabetes is primarily related to birth weight and body mass index. AB - OBJECTIVE: To clarify the effects of insulin therapy on ovarian androgen production, hyperandrogenism and polycystic ovary syndrome (PCOS) in adolescents and young women with type 1 diabetes (T1D). DESIGN: Case-control study. SETTING: Children's research hospital. PATIENT(S): Fifty-four consecutive T1D subjects (age, 15-25 years), without residual endogenous insulin secretion, treated by intensive insulin therapy (multiple injection therapy [MI] or continuous SC insulin infusion [CSII]); and one-hundred fifty age-matched healthy women. INTERVENTION(S): Analysis of the prevalence and risk factors of ovarian hyperandrogenism and PCOS in T1D adolescents and young women. MAIN OUTCOME MEASURE(S): Biometric, glycemic, and metabolic parameters. Evaluation of androgen levels and ovary ultrasound during the early follicular phase of the menstrual cycle. RESULT(S): Androgen levels were significantly higher in T1D subjects than in the control group (T, 68.8 +/- 23.4 vs. 46.1 +/- 20.8 ng/dL). Four subjects (7.4%) were affected by PCOS according to the Rotterdam criteria. No correlation was evident between HbA1c% and androgen levels. No significant differences were evident between subjects on MI or CSII therapy. Multivariable linear regression analysis showed a direct and independent effect of age and body mass index on T levels. T levels were also negatively affected by birth weight. CONCLUSION(S): Androgen levels are significantly increased in T1D adolescents and young women treated by intensive insulin therapy. The presence and severity of ovarian hyperandrogenism seem to be primarily related to common risk factors such as age, low birth weight, overweight, and obesity. PMID- 21982727 TI - Metformin reduces risk of ovarian hyperstimulation syndrome in patients with polycystic ovary syndrome during gonadotropin-stimulated in vitro fertilization cycles: a randomized, controlled trial. AB - OBJECTIVE: To test whether metformin administration reduces the incidence of ovarian hyperstimulation syndrome (OHSS) in infertile high-risk patients with polycystic ovary syndrome (PCOS) who have been treated with gonadotropins for IVF. DESIGN: Parallel, randomized, double-blind, placebo-controlled clinical trial. SETTING: Academic departments, general hospital, and IVF centers. PATIENT(S): One hundred twenty patients with PCOS at high risk for OHSS. INTERVENTION(S): Gonadotropins ovarian stimulation for IVF and metformin (500 mg three times daily) or placebo tablets (three times daily). MAIN OUTCOME MEASURE(S): The primary end point of the current clinical trial was the rate of OHSS. Anthropometric and reproductive data were evaluated. RESULT(S): The total OHSS and cancellation rates were significantly reduced in patients treated with metformin. The relative risk for OHSS was of 0.28 (95% confidence interval, 0.11 0.67). With metformin the stimulation length and the total amount of gonadotropins used were significantly increased, whereas the peak E(2) levels were significantly reduced. CONCLUSION(S): In patients with PCOS who are at high risk for OHSS and who have been stimulated with gonadotropins for IVF cycles, metformin reduces the risk of OHSS by modulating the ovarian response to the stimulation. REGISTRATION ID NUMBER FROM CLINICALTRIALS.GOV: NCT01233206. PMID- 21982728 TI - Pregnancy with cervical dysgenesis. AB - OBJECTIVE: To report a case of cervical dysgenesis in a patient who became pregnant through IVF and transmyometrial ET. DESIGN: Case report. SETTING: King Fahad Medical City. PATIENT(S): A 28-year-old nulligravida with cervical dysgenesis who underwent IVF and transmyometrial ET. INTERVENTION(S): Controlled ovarian hyperstimulation, IVF, and transmyometrial ET. MAIN OUTCOME MEASURE(S): Successful intrauterine pregnancy. RESULT(S): Single intrauterine pregnancy was achieved 30 days after transmyometrial ET. CONCLUSION(S): Successful pregnancy is possible in similar patients, eliminating the need for reconstructive surgery. PMID- 21982729 TI - Seminal leukocytes and clinical outcomes with donor sperm insemination. AB - OBJECTIVE: To report the level of leukocytospermia in fertile donors' semen. Surprisingly, seminal leukocytes protect fertilization properties of sperm and are associated with normal or improved assisted reproductive technology outcomes in infertility patients. This raises the question of whether leukocytospermia exists in fertile men as well. We report a study of sperm donors who, by law in France, have to be of proven fertility. DESIGN: Retrospective analysis. SETTING: University laboratory. PATIENT(S): One hundred fifty-five donors were selected for cryobanking. Results of their sperm analyses were compared with those from 10,242 infertile men. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The men's first ejaculate was studied by cytologic analysis to determine the round cell and polymorphonuclear cell (PMN) contents. A total of 3,875 donor sperm inseminations (DSIs) were performed, and their outcomes were analyzed over an 8-year period. RESULT(S): PMN is more elevated in semen from infertility patients than in semen from fertile donors, but some donors (6.5%) had high leukocytospermia (>=10(6)/mL). The post-DSI pregnancy rate was increased when round cells were present (P<.02) but not with higher PMN concentrations. Furthermore, high leukocytospermia was associated with an increased post-DSI miscarriage rate. CONCLUSION(S): In fertile donors, as in infertility patients, high leukocytospermia (>10(6)/mL) is associated with a normal pregnancy rate but an increased percentage of early pregnancy loss. PMID- 21982730 TI - Posthumous assisted reproduction: a survey of attitudes of couples seeking fertility treatment and the degree of agreement between intimate partners. AB - OBJECTIVE: To study attitudes about posthumous assisted reproduction (PAR) in individuals presenting for assisted reproduction, to examine the degree of concordance of attitudes within couples, and to determine whether individuals can accurately predict the attitudes of their intimate partners. DESIGN: Cross sectional survey. SETTING: University-based fertility center. PATIENT(S): One hundred six couples presenting for an initial fertility evaluation. INTERVENTION(S): Anonymous survey completed independently by each partner. MAIN OUTCOME MEASURE(S): 1) individual attitudes about PAR, 2) the rate of concordance in attitudes within couples, and 3) the ability of individuals to predict their partner's attitudes. RESULT(S): Approximately 78% of individuals stated they would permit PAR. Couples expressed concordant attitudes about 75% of the time. Statistically, women and men were equivalent in correctly predicting their partner's attitudes (79% vs. 71%). CONCLUSION(S): Although most individuals presenting for fertility treatment would agree to PAR, there was also a notable portion that stated that they would not consent with the process. Although most couples had concordant attitudes, discordance was also prevalent. Individuals often, but not always, were able to predict their partner's attitudes about PAR. PMID- 21982731 TI - Lipoprotein profiles in Mexican American and non-Hispanic white women with polycystic ovary syndrome. AB - OBJECTIVE: To compare lipid profiles between Mexican American and non-Hispanic white women with polycystic ovary syndrome (PCOS). DESIGN: Cross-sectional analysis using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. SETTING: University gynecology service. PATIENT(S): Self-identified Mexican Americans (n = 71) and non-Hispanic whites (n = 120) with PCOS defined by the 2003 European Society of Human Reproduction and Embryology and American Society of Reproductive Medicine consensus. INTERVENTION(S): Serum drawn from fasting state followed by oral glucose tolerance test. MAIN OUTCOME MEASURE(S): Age, body mass index (BMI), androgens, cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, fasting, and minimal model analyses of insulin sensitivity. RESULT(S): Mexican American women were more insulin resistant than non-Hispanic whites, but cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and calculated non-HDL cholesterol levels were similar. BMI inversely correlated with HDL cholesterol and positively with triglycerides. Approximately half of both ethnic groups had at least one lipid level in the low (HDL) or high (cholesterol, triglycerides, and LDL cholesterol) range according to National Cholesterol Education Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults guidelines. CONCLUSION(S): Despite greater insulin resistance among Mexican Americans with PCOS, lipid levels were similar to those of age- and weight matched non-Hispanic whites. Obesity adversely affected lipid levels-primarily HDL cholesterol and triglycerides-in both groups. The prevalence of dyslipidemia was approximately 50% in each ethnic group. PMID- 21982732 TI - General imprinting status is stable in assisted reproduction-conceived offspring. AB - OBJECTIVE: To evaluate whether the genomic imprinting status of assistant reproductive technology (ART)-conceived offspring is stable. DESIGN: Prospective clinical observational study. SETTING: In vitro fertilization (IVF) center, university-affiliated teaching hospital. PATIENT(S): Sixty ART-conceived babies (30 IVF and 30 intracytoplasmic sperm injection [ICSI]) and 60 naturally conceived babies. INTERVENTION(S): Collection of umbilical cord blood and peripheral blood samples. MAIN OUTCOME MEASURE(S): Expression profile was examined by microarray and real-time reverse-transcription polymerase chain reaction (PCR), allele-specific expression was studied by direct sequencing after PCR, and DNA methylation status was investigated by sodium bisulfite sequencing. RESULT(S): Hierarchic clustering demonstrated no obvious clustering between the ART- and naturally conceived offspring, suggesting similar genomic imprinting expression between the two groups. Three differentially expressed genes were identified in ART-conceived offspring, with PEG10 and L3MBTL up-regulated and PHLDA2 down-regulated. Allele-specific expression of the differentially expressed imprinted genes was maintained in the majority of the ART- and naturally conceived offspring. However, in one ICSI case, monoallelic expression of L3MBTL was disrupted and all CpGs were completely unmethylated. These were not inherited from the parents. CONCLUSION(S): The global profile of imprinting is stable in children conceived through ART. However, imprinting of a few specific imprinted genes may be vulnerable in a fraction of ART-conceived children. PMID- 21982733 TI - Profiling hydroxycinnamoyl-coenzyme A thioesters: unlocking the back door of phenylpropanoid metabolism. AB - In plants, 20 to 30% of photosynthetically fixed carbon is directed toward lignin and other phenylpropanoid compounds for which hydroxycinnamoyl-coenzyme A (CoA) esters are key intermediates. CoA thioesters, ubiquitous metabolites found in all living cells (often at trace levels), have traditionally been challenging to measure. Here we report a hydrophilic interaction liquid chromatography (HILIC) method, coupled with tandem mass spectrometry (MS/MS), that allows simultaneous sensitive quantification of previously undetectable hydroxycinnamoyl-CoA esters and an extended range of acyl-CoAs from plant tissues. This method provides rapid liquid chromatography (LC) analysis (10 min/sample) and the ability for qualitative assessment of acyl-CoAs by MS/MS precursor ion scanning. PMID- 21982734 TI - Disequilibrium in naturally occurring radioactive series in some phosphate ores. AB - Eight phosphate ore samples from Egypt and Saudi Arabia were studied by atomic absorption spectrometry for the Bi, Pb, Th and Al concentrations in ppm or ppb or per cent. Also X-ray diffraction spectrometry was applied for determining the mineral and chemical composition of the phosphate ore samples. A gamma spectrometry system, based on HPGe crystal, was applied for determining the concentrations of the radioactive elements in (238)U, (226)Ra and (232)Th series as well as (40)K, in Bq/kg dry weight. Concentrations in ppm were found to be from <10.0 to 20.48, from <7.50 to 27.30 and from <1.0 to 50.0 for Bi, Pb and Th, respectively. Al ranged from <0.05 to 3.13%. Major, minor and trace chemical and mineral compositions were assigned for each sample by XRD spectrometry. Concentrations of the different elements in both radioactive series, (238)U, (226)Ra and (232)Th were compared. Disequilibrium was found in both series. PMID- 21982735 TI - Determination of the influence factors of the radiopharmaceutical vials dimensions used for activimeter calibration at IPEN. AB - This paper presents the establishment of a quality control program and correction factors for the geometry of the vials used for distribution of radiopharmaceutical and activimeters calibration. The radiopharmaceutical produced by IPEN 67Ga, 131I, 201Tl and 99mTc had been tested using two different vials. Results show a maximum variation of 22% for 201Tl, and the minimum variation was 2.98% for 131I. The correction factors must be incorporated in the routine calibration of the activimeters. PMID- 21982736 TI - Assessment study for multi-barrier system used in radioactive borate waste isolation based on Monte Carlo simulations. AB - Radioactive waste generated from the nuclear applications should be properly isolated by a suitable containment system such as, multi-barrier container. The present study aims to evaluate the isolation capacity of a new multi-barrier container made from cement and clay and including borate waste materials. These wastes were spiked by (137)Cs and (60)Co radionuclides to simulate that waste generated from the primary cooling circuit of pressurized water reactors. Leaching of both radionuclides in ground water was followed and calculated during ten years. Monte Carlo (MCNP5) simulations computed the photon flux distribution of the multi-barrier container, including radioactive borate waste of specific activity 11.22KBq/g and 4.18KBq/g for (137)Cs and (60)Co, respectively, at different periods of 0, 15.1, 30.2 and 302 years. The average total flux for 100cm radius of spherical cell was 0.192photon/cm(2) at initial time and 2.73*10( 4)photon/cm(2) after 302 years. Maximum waste activity keeping the surface radiation dose within the permissible level was calculated and found to be 56KBq/g with attenuation factors of 0.73cm(-1) and 0.6cm(-1) for cement and clay, respectively. The average total flux was 1.37*10(-3)photon/cm(2) after 302 years. Monte Carlo simulations revealed that the proposed multi-barrier container is safe enough during transportation, evacuation or rearrangement in the disposal site for more than 300 years. PMID- 21982737 TI - Extensive or restricted ultrasound protocols to measure carotid intima-media thickness: analysis of completeness rates and impact on observed rates of change over time. AB - BACKGROUND: Ultrasound protocols to measure carotid intima-media thickness (CIMT) vary considerably with regard to carotid sites and angles that are assessed. Measurements from the carotid bifurcation and internal carotid artery are thought to be affected by large numbers of missing data. Actual published quantification of completeness rates and the relation with cardiovascular risk factors, however, is scarce. Also, it is currently unknown whether extensive ultrasound protocols including assessment of the carotid bifurcation and internal carotid artery add information in detecting rate of change in CIMT induced by drug therapy. These issues were addressed in this study using data from Measuring Effects on Intima Media Thickness: An Evaluation of Rosuvastatin (METEOR). METHODS: In METEOR, carotid ultrasound examinations were performed twice before randomization, once each at 6, 12, and 18 months after randomization, and twice after 24 months of study treatment. B-mode ultrasound images were obtained from the near and far walls of the left and right common carotid artery, bifurcation, and internal carotid artery at five predefined angles. Completeness of CIMT data was assessed by carotid site and by angle. A site was considered complete when any of the five angles was measured. The relation between completeness at baseline and cardiovascular risk factors was assessed using logistic regression analyses. Ultrasound protocols with a reduced number of carotid sites and angles were retrospectively constructed, and differences in the rate of change in maximum CIMT between ultrasound protocols were compared. RESULTS: At each visit, CIMT measurements from all 12 carotid sites were available for >94% of the participants. Incompleteness was the highest for near wall of the internal carotid artery and for the extreme angles (60 degrees and 300 degrees ). Of 12 risk factors examined, higher body mass index was related to incompleteness. Ultrasound protocols with a reduced number of angles resulted in similar estimates for the differences in rate of change in maximum CIMT. However, reductions in the number of sites gave results in the same direction but with different magnitudes and larger standard errors. CONCLUSIONS: High levels of complete data can be obtained with extensive ultrasound protocols that include measurement from the carotid bifurcation and internal carotid artery. A high body mass index contributes to incompleteness of CIMT measurements. Extensive ultrasound protocols are required to obtain the highest precision to observe a treatment effect and to fully cover the degree of atherosclerotic burden. PMID- 21982738 TI - Comparison of silk-elastinlike protein polymer hydrogel and poloxamer in matrix mediated gene delivery. AB - The silk-elastinlike protein polymer, SELP 815K, and poloxomer 407, a commercially available synthetic copolymer, were evaluated to compare their relative performance in matrix-mediated viral gene delivery. Using a xenogenic mouse tumor model of human head and neck squamous cell carcinoma, the efficacy of viral gene-directed enzyme prodrug therapy with these polymers was characterized by viral gene expression in the tumor tissue, tumor size reduction, and survivability with treatment. Viral injection in SELP 815K produced a greater level and more prolonged extent of gene expression in the tumor, a statistically greater tumor size reduction, a longer time until tumor rebound, and a significantly increased survivability, as compared to injection of virus alone or in Poloxamer 407. Safety of treatment with these polymers was evaluated in a non tumor bearing immunocompetent mouse model. Compared to virus injected alone or in Poloxamer 407, virus injected in SELP 815K had fewer and less severe indications of toxicity related to treatment as assessed by blood analysis, body weight, and histopathology of distant organs and the injection sites. Similar to virus alone or in Poloxamer 407, virus injected in SELP 815K elicited a mild injection site inflammatory response characterized primarily by a mononuclear leukocyte infiltrate and the formation of granulation tissue. Virus injected in SELP 815K resulted in fewer animals with elevated white blood cell counts and a less pronounced local toxicity reaction than was observed with virus in Poloxamer 407. In contrast to virus injected alone or in Poloxamer 407, which were not retained in the injection site tissues beyond week 1, SELP 815K was retained at the injection sites and by the end of the study (week 12), displayed limited absorption, and mild encapsulation. These results demonstrate the benefits of SELP 815K for matrix-mediated gene delivery over the injection of free virus and the injection of virus in Poloxamer 407. Virus in SELP 815K had greater efficacy of tumor suppression, promoted greater levels and greater duration of viral gene expression, and displayed reduced levels of injection site toxicity. Combining these performance and safety benefits with the degree of control with which they can be designed, synthesized and formulated, SELPs continue to show promise for their application in viral gene delivery. PMID- 21982739 TI - Towards crystal engineering via simulated pulmonary surfactant monolayers to optimise inhaled drug delivery. AB - PURPOSE: To generate theophylline monohydrate crystals underneath Langmuir monolayers composed of material expressed at the alveolar air-liquid interface. Such monolayers can act as nucleation sites to direct crystallisation. The approach offers a novel route to rationally engineer therapeutic crystals and thereby optimise inhaled drug delivery. METHODS: Langmuir monolayers consisting of either dipalmitoylphosphatidylcholine (DPPC) or a surfactant mix reflecting pulmonary surfactant were supported on an aqueous theophylline (5.7 mg/ml) subphase. The monolayers were compressed to surface pressures reflecting inhalation and exhalation (i.e. 5 mNm(-1) or 55 mNm(-1)) with a period of 16 h to allow crystallisation. Analysis involved scanning electron microscopy (SEM), atomic force microscopy (AFM) and powder X-ray diffraction (PXRD). RESULTS: Condensed isotherms were acquired, which signified surfactant-theophylline interaction. Theophylline monohydrate crystals were obtained and exhibited needle like morphology. SEM and AFM data highlighted regions of roughened growth along with smooth, stepwise growth on the same crystal face. The surfactant monolayers appeared to influence crystal morphology over time. CONCLUSIONS: The data indicate a favourable interaction between each species. The principal mechanism of interaction is thought to be an ion-dipole association. This approach may be applied to generate material with improved complementarity with pulmonary surfactant thus enhancing the interaction between inhaled drug particles and internal lung surfaces. PMID- 21982740 TI - The effects of apparatus design and test procedure on learning and memory performance of C57BL/6J mice on the Barnes maze. AB - The Barnes maze is a visuo-spatial learning and memory test originally designed for use with rats, and later adapted for use with mice. The Barnes maze design and test procedure vary across studies using mice, but the effects of variation in Barnes maze design and test procedure on learning and memory in mice have not yet been investigated. Therefore the present experiment investigates whether test procedures, such as the number of habituation trials and parameters of the probe trial (correct zone size and trial length) influence learning and memory performance on three Barnes maze designs that differed in size and the presence of a wall with intra-maze visual cues. Performance was compared across the three mazes to determine how apparatus design influences visuo-spatial cue use. The number of habituation trials and parameters of the probe trial had small effects on learning and memory performance. Apparatus design, had little effect on acquisition performance but had a significant effect on memory performance. Mice on a maze with a small diameter, external wall and intra-maze visual cues had very poor visuo-spatial memory relative to mice tested on small and large diameter mazes without a wall or intra-maze visual cues. Assessment of visuo spatial cue use indicated that mice do not rely on visuo-spatial cues to locate the escape hole on the small-diameter maze with a wall and intra-maze visual cues, but show reliable visuo-spatial cue use on small or large diameter mazes with no wall. These results indicate that apparatus design influences search strategy use and memory performance on the Barnes maze, and that including a wall around the edge of the Barnes maze decreases visuo-spatial cue use. PMID- 21982741 TI - Mannitol-facilitated perfusion staining with 2,3,5-triphenyltetrazolium chloride (TTC) for detection of experimental cerebral infarction and biochemical analysis. AB - A simple method to quantify cerebral infarction has great value for mechanistic and therapeutic studies in experimental stroke research. Immersion staining of unfixed brain slices with 2,3,5-triphenyltetrazolium chloride (TTC) is a popular method to determine cerebral infarction in preclinical studies. However, it is often difficult to apply immersion TTC-labeling to severely injured or soft newborn brains in rodents. Here we report an in vivo TTC perfusion-labeling method based on osmotic opening of blood-brain-barrier with mannitol pretreatment. This new method delineates cortical infarction correlated with the boundary of morphological cell injury, differentiates the induction or subcellular redistribution of apoptosis-related factors between viable and damaged areas, and easily determines the size of cerebral infarction in both adult and newborn mice. Using this method, we confirmed that administration of lipopolysaccharide 72 h before hypoxia-ischemia increases the damage in neonatal mouse brains, in contrast to its effect of protective preconditioning in adults. These results demonstrate a fast and inexpensive method that simplifies the task of quantifying cerebral infarction in small or severely injured brains and assists biochemical analysis of experimental cerebral ischemia. PMID- 21982742 TI - Plac8 is an inducer of C/EBPbeta required for brown fat differentiation, thermoregulation, and control of body weight. AB - Brown adipocytes oxidize fatty acids to produce heat in response to cold or to excessive energy intake; stimulation of brown fat development and function may thus counteract obesity. Brown adipogenesis requires activation of the transcription factor C/EBPbeta and recruitment of the zinc finger protein Prdm16, but upstream inducers of these proteins are incompletely defined. Here, we show that genetic inactivation of Plac8, a gene encoding an evolutionarily conserved protein, induces cold intolerance, and late-onset obesity, as well as abnormal morphology and impaired function of brown adipocytes. Using brown preadipocyte lines we show that Plac8 is required for brown fat differentiation, that its overexpression induces C/EBPbeta and Prdm16, and that upon induction of differentiation Plac8 associates with C/EBPbeta and binds to the C/EBPbeta promoter to induce its transcription. Thus, Plac8 is a critical upstream regulator of brown fat differentiation and function that acts, at least in part, by inducing C/EBPbeta expression. PMID- 21982743 TI - The arrestin domain-containing 3 protein regulates body mass and energy expenditure. AB - A human genome-wide linkage scan for obesity identified a linkage peak on chromosome 5q13-15. Positional cloning revealed an association of a rare haplotype to high body-mass index (BMI) in males but not females. The risk locus contains a single gene, "arrestin domain-containing 3" (ARRDC3), an uncharacterized alpha-arrestin. Inactivating Arrdc3 in mice led to a striking resistance to obesity, with greater impact on male mice. Mice with decreased ARRDC3 levels were protected from obesity due to increased energy expenditure through increased activity levels and increased thermogenesis of both brown and white adipose tissues. ARRDC3 interacted directly with beta-adrenergic receptors, and loss of ARRDC3 increased the response to beta-adrenergic stimulation in isolated adipose tissue. These results demonstrate that ARRDC3 is a gender sensitive regulator of obesity and energy expenditure and reveal a surprising diversity for arrestin family protein functions. PMID- 21982745 TI - Sarcopenia and predictors of the fat free mass index in community-dwelling and assisted-living older men and women. AB - The purpose of this study was to assess the relationship of the fat free mass index (FFMI), an indicator of sarcopenia in older adults, to anthropometric, gait, balance, and strength measures. We hypothesized that strength, balance, and mobility measures will correlate, and could be used to predict FFMI in older adults. Thirty-three older adults (81.5+/-7.9 years) participated. Fat free mass (FFM) was measured using Air-Displacement Plethysmography (ADP). Anthropometric measures, maximum handgrip (MG) and quadriceps strength were quantified. Clinical tests included the Berg Balance Scale (BBS), Dynamic Gait Index (DGI), and the Timed-up and Go (TUG) test. Finally, variability measures in gait and balance were calculated. Means, standard deviations (SD), correlations and multiple linear regression statistical analyses were then performed using functional predictor variables for FFMI. In total, 54.5% males and 36.3% females in our population were classified sarcopenic. FFMI correlated only to waist circumference (Total population (Pop), R(2)=0.649 p<0.01; Sarcopenics (Sarc), R(2)=0.636, p<0.05) and maximum grip strength (Pop, R(2)=0.633, p<0.01; Sarc, R(2)=0.771, p<0.01), nullifying our hypothesis. Multiple linear regression analyses revealed waist circumference, maximum handgrip strength, greater variability of time spent in double support, and anterior-posterior balance variability predicted 70.7% of the variance within the population. Results demonstrate a successful predictor model for FFMI based on a combination of strength, circumference and gait/balance variance measures. The ability to predict FFMI based on these variables will facilitate the diagnosis of sarcopenia in older adults. PMID- 21982744 TI - Autophagy, nutrition and immunology. AB - Turnover of cellular components in lysosomes or autophagy is an essential mechanism for cellular quality control. Added to this cleaning role, autophagy has recently been shown to participate in the dynamic interaction of cells with the surrounding environment by acting as a point of integration of extracellular cues. In this review, we focus on the relationship between autophagy and two types of environmental factors: nutrients and pathogens. We describe their direct effect on autophagy and discuss how the autophagic reaction to these stimuli allows cells to accommodate the requirements of the cellular response to stress, including those specific to the immune responses. PMID- 21982746 TI - Sexual conflict in viscous populations: the effect of the timing of dispersal. AB - In recent years, there has been increasing theoretical and empirical examination of how sexual conflict can arise between males and females. However, much this work has implicitly assumed that interactions take place in panmictic populations with complete dispersal, where interactions are between unrelated individuals. Here, we examine the consequences of limited dispersal and population structure for the evolution of a male phenotype that is associated with the males pre- and post-copulatory reproductive success, using an inclusive-fitness based analysis applied to group-structured populations. We show that: (i) the sex-specific timing of the dispersal phase of the life cycle can drive the evolution of sexual conflict; (ii) the inclusive fitness of a female in this conflict is determined solely by direct (i.e. personal) effects on its own competitive ability. Our analysis is supported by results from individual-based simulations of multi-level selection. Our results support the suggestion that kin selection can influence the evolution of sexual conflict, but reveal that such a role might be more complex than previously appreciated when sex-specific life histories are taken into consideration. We discuss the implications of our results for sexual conflict in various species of insects, but focus primarily on dipteran flies of the family Sepsidae. PMID- 21982747 TI - Does excessive play of violent first-person-shooter-video-games dampen brain activity in response to emotional stimuli? AB - The present case-control study investigated the processing of emotional pictures in excessive first-person-shooter-video-players and control persons. All participants of the fMRI experiment were confronted with pictures from four categories including pleasant, unpleasant, neutral content and pictures from the first-person-shooter-video-game 'Counterstrike'. Compared to controls, gamers showed a significantly lower activation of the left lateral medial frontal lobe while processing negative emotions. Another interesting finding of the study represents the higher activation of frontal and temporal brain areas in gamers when processing screen-shots from the first-person-shooter-video-game 'Counterstrike'. Higher brain activity in the lateral prefrontal cortex could represent a protection mechanism against experiencing negative emotions by down regulating limbic brain activity. Due to a frequent confrontation with violent scenes, the first-person-shooter-video-gamers might have habituated to the effects of unpleasant stimuli resulting in lower brain activation. Individual differences in brain activations of the contrast Counterstrike>neutral pictures potentially resemble the activation of action-scripts related to the video-game. PMID- 21982748 TI - Perceptual and not physical eye contact elicits pupillary dilation. AB - Eye contact is important to share communication during social interactions. However, how accurately humans can perceive the gaze direction of others toward themselves and whether pupils dilate when humans consciously or unconsciously perceive own eyes are looked by others remain unclear. In this study, we examined the relationship between the explicit perception of looking into each other's eyes and the implicit physiological response of pupillary dilation by using an original face-to-face method. We found that humans do not correctly detect the gaze direction of others. Furthermore, one's pupils dilated when one gazed at others' eyes. Awareness of others' gaze on one's eyes, rather than the actual focusing of other's gaze on one's eyes, enhanced pupillary dilation. Therefore, physiological responses are caused not when people actually look into each other's gaze, but when the consciousness of other's gaze is activated, which suggests that eye contact often involves one-way communication. PMID- 21982751 TI - Pharmaceutical care to patients treated with antidepressants. AB - Depression is considered one of the ten most disabling conditions on the planet, causing physical, personal and social limitations. Antidepressants are the most commonly used drug treatment for eliminating or controlling the symptoms of depression. A variety of factors can contribute to treatment abandonment, particularly severe side effects. The present article is aimed to provide information and guidelines on the development of a pharmacotherapy follow-up program for patients treated with antidepressant medication. According to this practice, the pharmacist evaluates whether the three following requirements of a proper pharmacotherapy are being observed: need, effectiveness and safety. If one of these requirements is not met, the pharmacist seeks to solve the problem, by intervening in the pharmacotherapy, within the scope of his/her skills. Pharmaceutical care is aimed to improve adherence to treatment and minimize side effects, as well as the occurrence of drug interactions. Thus, the present article presents and discusses the main strategies of pharmaceutical care to achieve the proposed objectives. PMID- 21982750 TI - Translational research: creating excellent evidence-based pediatric nursing practice. PMID- 21982749 TI - Sgp3 and Sgp4 control expression of distinct and restricted sets of xenotropic retroviruses encoding serum gp70 implicated in murine lupus nephritis. AB - The envelope glycoprotein gp70 of endogenous retroviruses implicated in murine lupus nephritis is secreted by hepatocytes and its expression is controlled by Sgp3 (serum gp70 production 3) and Sgp4 loci derived from lupus-prone mice. Among three different endogenous retroviruses (ecotropic, xenotropic and polytropic), xenotropic viruses are considered to be the major source of serum gp70. Although the abundance of xenotropic viral gp70 RNA in livers was up-regulated by the presence of these two Sgp loci, it has not yet been clear whether Sgp3 and Sgp4 regulate the expression of a fraction or multiple xenotropic viruses present in mouse genome. To address this question, we determined the genetic origin of xenotropic viral sequences expressed in wild-type and two different Sgp congenic C57BL/6 mice. Among 14 xenotropic proviruses present in the C57BL/6 genome, only two proviruses (Xmv10 and Xmv14) were actively transcribed in wild-type C57BL/6 mice. In contrast, Sgp3 enhanced the transcription of Xmv10 and induced the transcription of three additional xenotropic viruses (Xmv15, Xmv17 and Xmv18), while Sgp4 induced the expression of a different xenotropic virus (Xmv13). Notably, stimulation of TLR7 in Sgp3 congenic C57BL/6 mice led to a highly enhanced expression of potentially replication-competent Xmv18. These results indicated that Sgp3 and Sgp4 independently regulated the transcription of distinct and restricted sets of xenotropic viruses in trans, thereby promoting the production of nephritogenic gp70 autoantigens. Furthermore, the induced expression of potentially replication-competent xenotropic viruses by Sgp3 may contribute to the development of autoimmune responses against gp70 through the activation of TLR7. PMID- 21982752 TI - Lipopolysaccharide-induced lung injury: role of P2X7 receptor. AB - RATIONALE: P2X7 receptors have been involved in inflammatory and immunological responses, and their activation modulates pro-inflammatory cytokines production by LPS-challenged macrophages. OBJECTIVES: To determine the role of P2X7R in LPS induced acute lung injury in mice. METHODS: Wild-type (C57BL/6) and P2X7 knockout mice received intratracheal injection of saline or Escherichia coli LPS (60 MUg). After 24h, changes in lung mechanics were determined by the end-inflation occlusion method. Bronchoalveolar lavage was performed, and lungs were harvested for measurement of morphometry, fibers content, inflammatory cells and cytokine expression by histochemistry and immunohistochemistry. RESULTS: Compared with saline, LPS increased lung mechanical parameters, mast cell, collagen and fibronectin deposition in lung parenchyma, as well as nitric oxide and lactate dehydrogenase release into bronchoalveolar fluid in wild-type, but not in P2X7R knockout mice. Alveolar collapse, lung influx of polymorphonuclear and CD14(+) cells, as well as TGF-beta, MMP-2, and IL-1beta release were higher in wild-type than knockout LPS-challenged mice, while MMP-9 release where similar between the two genotypes. LPS increased macrophage immunoreactivity in lung tissue in both genotypes, but macrophages were not activated in the P2X7R knockout mice. Furthermore, LPS administration increased P2X7R immunoexpression in lung parenchyma in wild-type mice, and TLR4 in both wild-type and P2X7R knockout mice. CONCLUSION: P2X7 receptors are implicated in the pathophysiology of LPS-induced lung injury, modulating lung inflammatory and functional changes. PMID- 21982753 TI - Fatalities on Austrian ski slopes during a 5-year period. AB - BACKGROUND: While the mean injury rate from snow sports in Austria is low (less than 2 injuries per 1000 skier days), there is little information about fatalities on Austrian ski slopes. OBJECTIVE: The purpose of this study was to evaluate incidence and causes of fatalities among recreational skiers and snowboarders over a 5-season period on Austrian ski slopes. METHODS: All traumatic and nontraumatic fatal ski accidents from the 2005-2006 through the 2009-2010 winter season were compiled by members of the Federal Ministry of the Interior. Data on age, gender, nationality, gear used, altitude, accident cause, primary cause of death, and helmet use were collected. The number of fatalities was related to a million skier days during this 5-year period. RESULTS: In total, 207 fatalities were registered during this time period. An overall incidence of 0.79 deaths per million skier days was calculated. Mean age was 50.9 +/- 17.7 years. More than 85% of all fatalities occurred in males and 93.1% in skiers. Mean altitude was 1706.1 +/- 517.7 m above sea level. In total, 52.7% were nontraumatic deaths, with the majority (73%) attributed to cardiac arrest. Regarding traumatic deaths, 41.2% died after a fall, 18.6% after collision with another skier, and 35.1% after an impact with a solid object. Head injury was the primary cause of death in 46.4% of traumatic deaths. CONCLUSIONS: Death is a rare event in recreational winter sports on Austrian ski slopes. Nevertheless, awareness of potential risk factors and common dangers may impact snow riders' behavior and help reduce the incidence of on-slope fatalities. PMID- 21982755 TI - Keeping your cool: a case study of a female explorer's solo North Pole expedition. AB - OBJECTIVE: This study explored stress and coping experiences during a solo expedition to the North Pole using concurrent and retrospective methods. METHODS: A 47-year-old female explorer, with 12 years of polar experience, completed a daily diary during the expedition. On return, 2 semistructured interviews were completed to identify the challenges and coping efforts perceived as being most pertinent during her expedition. RESULTS: Inductive coding identified 4 broad stressors, including environmental conditions, personal challenges, supporting resources, and expedition progress. CONCLUSIONS: Findings highlight the importance of expedition preparation in establishing coping efficacy in managing the extreme demands placed upon polar explorers. Findings also evidence idiosyncrasies in the choice and application of coping strategies and, thus, highlight the need to avoid generalizations regarding coping outcomes. PMID- 21982756 TI - In response to "Wilderness Medical Society Practice Guidelines for the Prevention and Treatment of Frostbite". PMID- 21982757 TI - Immune responses to exercising in a cold environment. AB - Cold temperature and exercise independently impose stress on the human body that can lead to circulatory and metabolic changes, and depress the immune system. Multiple stressors applied together may amplify this immunodepression, causing greater immune impairment and heightened infection risk than with either stressor alone. As such, winter athletes and other persons who work or physically exert themselves in cold temperatures may have greater levels of stress-induced immune impairment than would be expected under mild temperatures. This review examines the literature regarding changes to physiological and immunological parameters arising from exposure to cold temperatures and to exercise. Even brief exposure to cold leads to increased levels of norepinephrine and cortisol, lymphocytosis, decreased lymphoproliferative responses, decreased levels of TH1 cytokines and salivary IgA, and increased lactate levels during exercise. Whether these changes lead to increased susceptibility to infection, as suggested by some epidemiological reports, remains to be determined. Although there is some evidence that exercising in temperatures near 5 degrees C leads to greater immune impairment compared to exercising in milder temperatures, there is a need to explore the effects of exercise on immunity in the subfreezing conditions typically encountered by winter athletes. This is required to fully determine the extent to which performing vigorous exercise in subfreezing temperatures amplifies exercise-induced immune impairment and infection risk. PMID- 21982758 TI - Improving sleep at altitude: a comparison of therapies. AB - OBJECTIVE: This study aimed to compare 3 treatment modalities during sleep at an altitude of 5300 m to identify strategies for reducing the incidence of periodic breathing at high altitude. METHODS: Fifteen trekkers, with identical ascent profiles and no signs or symptoms of altitude illness, served as subjects. All study participants arrived at 5300 m after a gradual ascent from 1300 m. On their second night at 5300 m, subjects were randomly assigned (with a computer-based random assignment procedure) to 1 of 4 different treatment groups: control (n = 4); 1 L/min O(2) via a demand system during sleep (n = 3); 1 L/min O(2)/CO(2) mix (1.5% CO(2)) via a demand system during sleep (n = 4); or 125 mg acetazolamide 30 minutes before bedtime (n = 4). Heart rate, respiration rate, blood oxygen saturation, tidal volume, minute volume, and apnea hypopnea index were measured. RESULTS: Upon comparing the 4 groups, there were no statistically significant differences between the variables. One-way analysis of variance indicated a trend toward statistical significance for SaO(2) between groups (F = 2.9, P = .08), and Tukey Honestly Significant Difference (HSD) post hoc tests indicated a trend in the SaO(2) difference between the 1 L/min oxygen and control groups (P = .07). While 1-way analysis of variance suggested no difference for respiratory rate between groups (F = 2.5, P = .1), Tukey HSD indicated a trend in statistical difference of the respiratory rate between 1 L/min O(2) and 1 L/min O(2)/CO(2) mixture (P = .08). CONCLUSIONS: These statistical trends found between control and treatment groups indicate that further study is warranted. PMID- 21982759 TI - Mapping the lateral extent of human cadaver decomposition with soil chemistry. AB - Soil below decomposing cadavers may have a different lateral spatial extent depending upon whether scavengers have access to the human cadaver or not. We examined the lateral spatial extent of decomposition products to a depth of 7cm of soils beneath two decomposing corpses, one in which the subject was autopsied, unclothed and placed under a wire cage to restrict scavenger access and one in which the subject was not autopsied, unclothed and exposed to scavengers. The two bodies had accumulated degree days (ADD) of 5799 and 5469 and post mortem interval (PMI) of 288 and 248d, respectively. The spatial extent for dissolved organic carbon (DOC) and organic nitrogen (DON) for both bodies was large but similar suggesting some movement off site for both compounds. Mean DOC was 1087+/ 727 and 1484+/-1236MUgg(-1) dry soil under the two corpses relative to 150+/ 68MUgg(-1) in upslope control soils. Sulfate tended to have 'hot spots' of lower values relative to the control soils indicative of anaerobic respiration. pH was lower and electrical conductivity was higher in the soil under both decomposing cadavers relative to control soils. Some of the nutrients examined downslope of the human remains were significantly higher than control soils upslope suggesting movement of decomposition products off-site which could be an important factor when using human remains detector dogs. PMID- 21982760 TI - Low lumbar burst fractures: a unique fracture mechanism sustained in our current overseas conflicts. AB - BACKGROUND CONTEXT: The most common location for burst fractures occurs at the thoracolumbar junction, where the stiff thoracic spine meets the more flexible lumbar spine. With our current military conflicts in Iraq and Afghanistan, we have seen a disproportionate number of low lumbar burst fractures. PURPOSE: To report our institutional experience in the management of low lumbar burst fractures. STUDY DESIGN: Retrospective review. METHODS: We performed a retrospective review of medical records and radiographs for all patients treated at our institution with combat-related injuries and thoracolumbar fractures. We included all patients who had sustained a burst fracture from T12 to L5 and had at least 1-year clinical follow-up. RESULTS: Thirty-two patients sustained burst fractures. Nineteen patients (59.4%) had low lumbar (L3-L5) burst fractures, and 12 patients (37.5%) had thoracolumbar junction (T12-L2) burst fractures as their primary injury. Additionally, seven patients sustained less severe burst fractures at an additional level. One patient sustained burst fractures at both upper and lower lumbar levels. Of the low lumbar fractures, 52.6% had evidence of neurologic injury, two of which were complete. Similarly, in the upper lumbar group, 58.2% sustained a neurologic injury, two of which were complete. Twenty two patients underwent surgical intervention, complicated by infection in 18%. At most recent follow-up, all but one patient with presenting neurologic injury had persistent deficits. CONCLUSION: Low lumbar burst fractures are the predominant combat-related spine injury in our current military conflicts. The rigidity offered by current body armor may effectively lower the transition zone that normally occurs at the thoracolumbar junction, thereby, transferring forces into the lower lumbar spine. Increased awareness of this fracture pattern is warranted by all surgeons because of unique clinical challenges associated with its treatment. Although the incidence is increased in the military population, other surgeons may be involved with long-term care of these patients on completion of their military service. PMID- 21982761 TI - Trapeziometacarpal joint osteoarthritis after proximal row carpectomy: treatment with a total joint arthroplasty. AB - The authors report a case of trapeziometacarpal osteoarthritis in a 58-year-old woman with low functional demand. The patient had a proximal row carpectomy for posttraumatic radiocarpal arthritis. The authors decided to perform arthroplasty using a total GUEPAR trapeziometacarpal prosthesis to conserve carpal stability of the first column. Eight years after the surgery, the patient is free of pain and her thumb movement is similar to the opposite thumb. No radiographic changes were observed. No similar cases have been reported in the literature. Prosthesis insertion could be a reasonable option for this indication to give long-term painless mobility and stability. PMID- 21982762 TI - Binding of L-selectin to its vascular and extravascular ligands is differentially regulated by pH. AB - Ligands for L-selectin, a leukocyte adhesion molecule, are expressed in high endothelial venules (HEVs) in lymph nodes and extravascular tissues, such as renal tubules. Here, we report that the binding of L-selectin to its vascular and extravascular ligands is differentially regulated by pH. The optimal L-selectin dependent binding of leukocytes to HEVs was observed at pH 7.4, a physiological pH in the blood. In contrast, the optimal binding of leukocytes to the renal tubules was observed at pH 5.6. Consistently, optimal binding of soluble recombinant L-selectin to a major vascular ligand, 6-sulfo sialyl Lewis X, was observed at pH 7.4. Binding to extravascular ligands, such as chondroitin sulfate (CS) B, CS E and heparan sulfate, occurred at pH 5.6. Under physiological shear stress ranging from 1 to 2 dynes/cm(2), maximal leukocyte rolling on vascular ligands was observed at pH 6.8 to 7.4, and no rolling was detected at pH conditions below 5.6. These findings suggest that the pH environment is one important factor that determines leukocyte trafficking under physiological and pathological conditions. PMID- 21982763 TI - Calpastatin is regulated by protein never in mitosis gene A interacting-1 (PIN1) in endothelial cells. AB - The peptidyl-proline isomerase, protein never in mitosis gene A interacting-1 (PIN1) binds and isomerizes proteins phosphorylated on serine/threonine before a proline. It was previously found that depletion of PIN1 greatly increased induction of cyclooxygenase-2 and inducible nitric oxide synthase by lowering calpain activity in murine aortic endothelial cells (MAEC). Here we investigated the effect of PIN1 on the endogenous inhibitor of heterodimeric MU- and m calpains, calpastatin. MAEC were transduced with small hairpin (sh) RNA to knock down PIN1 (KD) or an inactive Control shRNA. Cells were also treated with non targeted double stranded small inhibitory RNA (siRNA) or siRNA designed to deplete calpastatin. Despite reducing calpain activity, PIN1 KD did not significantly affect the expression of MU- and m-calpains, or calpastatin, compared to Control shRNA. Instead, depletion of PIN1 increased the inhibitory activity of calpastatin. Calpastatin co-immunoprecipitated with endogenous PIN1 and was pulled down with glutathione-S-transferase (GST)-PIN1 fusion protein. Adding GST-PIN1 to KD cell extracts lacking PIN1 reduced calpastatin inhibitory activity. Substrate binding and catalytic domain mutants of PIN1 failed to do so. These results suggest that protein interaction and the proline isomerase functions of PIN1 are required for it to inhibit calpastatin. Furthermore, depletion of calpastatin raised calpain activity and reduced calpain inhibitory activity to similar levels in KD and Control MAEC, indicating that calpastatin is required for PIN1 depletion to lower calpain activity. Thus, PIN1 apparently restrains the ability of calpastatin to inhibit calpain, maintaining calpain activity in endothelial cells. PIN1 may act directly via phosphorylated serine/threonine-proline motifs in calpastatin, or indirectly via other PIN1 substrates that control calpastatin. PMID- 21982764 TI - The role of TonEBP in regulation of AAD expression and dopamine production in renal proximal tubule cells upon hypertonic challenge. AB - Renal proximal tubule cells overexpress aromatic l-amino acid decarboxylase (AAD) to produce dopamine, which inhibits salt absorption in the hypertonic environment. We examined the effect of TonEBP on AAD expression in human proximal tubule epithelial cells, HK-2 cell line. Confocal microscopy showed that after 2h of exposure to the hypertonic medium, TonEBP accumulation in nuclei increased as compared to the isotonic control. The activated TonEBP enhanced the mRNA expression of the representative downstream genes (i.e., SMIT and TauT). Meanwhile, AAD protein abundance also increased with TonEBP activation. EMSA and luciferase reporter assay showed that TonEBP was involved in transcriptional regulation of AAD upon hypertonic stress. Inactivation of TonEBP by the p38 inhibitor SB203580, or TonEBP shRNA significantly reduced AAD expression, which was rescued by re-expressing Myc-tagged TonEBP. Up-regulation of AAD increased dopamine synthesis, and dopamine inhibited NKA activity in hypertonic condition. These results suggested that TonEBP played an important role in the epithelial cells of renal proximal tubule upon hypertonic stress by enhancing AAD expression, which could promote dopamine secretion to negative regulate NKA activity. The elucidation of a new mechanism described in this study combined with previous findings provides more insights into this issue. PMID- 21982765 TI - Poly(ADP-ribose) polymerase-1 protects from oxidative stress induced endothelial dysfunction. AB - BACKGROUND: Generation of reactive oxygen species (ROS) is a key feature of vascular disease. Activation of the nuclear enzyme poly (adenosine diphosphate [ADP]-ribose) polymerase-1 (PARP-1) is a downstream effector of oxidative stress. METHODS: PARP-1(-/-) and PARP-1(+/+) mice were injected with paraquat (PQ; 10 mg/kg i.p.) to induce intracellular oxidative stress. Aortic rings were suspended in organ chambers for isometric tension recording to analyze vascular function. RESULTS: PQ treatment markedly impaired endothelium-dependent relaxations to acetylcholine in PARP-1(-/-), but not PARP-1(+/+) mice (p<0.0001). Maximal relaxation was 45% in PQ treated PARP-1(-/-) mice compared to 79% in PARP-1(+/+) mice. In contrast, endothelium-independent relaxations to sodium nitroprusside (SNP) were not altered. After PQ treatment, l-NAME enhanced contractions to norepinephrine by 2.0-fold in PARP-1(-/-) mice, and those to acetylcholine by 3.3 fold, respectively, as compared to PARP-1(+/+) mice. PEG-superoxide dismutase (SOD) and PEG-catalase prevented the effect of PQ on endothelium-dependent relaxations to acetylcholine in PARP-1(-/-) mice (p<0.001 vs. PQ treated PARP 1(+/+) mice. Indomethacin restored endothelium-dependent relaxations to acetylcholine in PQ treated PARP-1(-/-) mice (p<0.05 vs. PQ treated PARP-1(+/+). CONCLUSION: PARP-1 protects from acute intracellular oxidative stress induced endothelial dysfunction by inhibiting ROS induced production of vasoconstrictor prostanoids. PMID- 21982766 TI - A 35 kDa antigenic protein from Shigella flexneri: in silico structural and functional studies. AB - Shigella flexneri serotype 2a is a major public health concern in the developing and under-developed countries which contributes to shigellosis endemic and mortality. Thus, there is an urgent need for a rapid diagnostic test for effective therapy and disease management. Previous study showed that a ~35 kDa antigenic protein from S. flexneri is a potential biomarker. We therefore modelled the three-dimensional structure of the antigen to probe its functionality which could aid in the development of an antigen-based diagnostic. Results showed that the antigen is a transmembrane protein consists of OmpA and OmpA-like domains. The OmpA domain is a beta-barrel embedded in the outer membrane with four surface-exposed extracellular loops. The OmpA-like domain is linked to the OmpA domain with a 17 amino acids linker and located in the periplasmic. Docking of peptidoglycan into the groove of OmpA-like domain might help in catalyzing the bacterial cell wall formation. Both domains are expected to be involved in the virulence, structural stability, pathogenesis and survival of Shigella thus made the 35 kDa protein a suitable shigellosis diagnostic biomarker. This structural elucidation will also enable a better identification of the epitope regions for the development of specific binders to the 35 kDa antigen. PMID- 21982767 TI - Hemagglutinating virus of Japan envelope (HVJ-E) can enhance the immune responses of swine immunized with killed PRRSV vaccine. AB - Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically detrimental pig pathogen that causes significant losses for the pig industry. The immunostimulatory effects of hemagglutinating virus of Japan envelope (HVJ-E) in cancer therapy and the adjuvant efficacy of HVJ-E have been previously evaluated. The objective of this study was to investigate the adjuvant effects of HVJ-E on immunization with killed PRRSV vaccine, and to evaluate the protective effects of this immunization strategy against virulent PRRSV infection in piglets. Next, the PRRSV-specific antibody response, lymphocyte proliferation, PRRSV-specific IL-2, IL-10 and IFN-gamma production, and the overall protection efficacy were evaluated to assess the immune responses of the piglets. The results showed that the piglets inoculated simultaneously with killed PRRSV vaccine and HVJ-E had a significantly stronger immune response than those inoculated with killed PRRSV vaccine alone. Our results suggest that HVJ-E could be employed as an effective adjuvant to enhance the humoral and cellular responses of piglets to PRRSV. PMID- 21982768 TI - Strongylophorine-8, a pro-electrophilic compound from the marine sponge Petrosia (Strongylophora) corticata, provides neuroprotection through Nrf2/ARE pathway. AB - Green plant-origin electrophilic compounds are a newly-recognized class of neuroprotective compounds that provide neuroprotection through activation of the Nrf2/ARE pathway. Electrophilic hydroquinones are of particular interest due to their ability to become electrophilic quinones upon auto-oxidation. Although marine organisms frequently produce a variety of electrophilic compounds, the detailed mechanisms of action of these compounds remain unknown. Here, we focused on the neuroprotective effects of strongylophorine-8 (STR8), a para-hydroquinone type pro-electrophilic compound from the sponge Petrosia (Strongylophora) corticata. STR8 activated the Nrf2/ARE pathway, induced phase 2 enzymes, and increased glutathione, thus protecting neuronal cells from oxidative stress. Microarray analysis indicated that STR8 induced a large number of phase 2 genes, the regulation of which is controlled by the Nrf2/ARE pathway. STR8 is the first example of a neuroprotective pro-electrophilic compound from marine organisms. PMID- 21982769 TI - miR-146a suppresses the sensitivity to interferon-alpha in hepatocellular carcinoma cells. AB - BACKGROUND: Interferon-based (IFN-based) therapy is effective in the treatment of advanced hepatocellular carcinoma (HCC). However, the issue of resistance to this therapy remains to be solved. The aim of this study was to identify microRNAs (miRNAs) that govern the sensitivity to IFN-alpha in HCC cells. METHODS: miRNA microarray analysis using IFN-alpha-resistant clones of PLC/PRF/5 (PLC-Rs) and their parental cells (PLC-P) was conducted. Changes in the anti-cancer effects of IFN-alpha were studied after gain-of-function and loss-of-function of the candidate miRNA. RESULTS: miR-146a expression was significantly higher in PLC-Rs than in PLC-P. miR-146a decreased the sensitivity to IFN-alpha through the suppression of apoptosis. Further experiments showed that miR-146a-related resistance to IFN-alpha was mediated through SMAD4. CONCLUSIONS: The results indicated that miR-146a regulated the sensitivity of HCC cells to the cytotoxic effects of IFN-alpha through SMAD4, suggesting that this miRNA could be suitable for prediction of the clinical response and potential therapeutic target in HCC patients on IFN-based therapy. PMID- 21982770 TI - Variation in Chst8 gene expression level affects PrPC to PrPSc conversion efficiency in prion-infected Mov cells. AB - The conversion of the endogenous cellular prion protein to an abnormally folded isoform is a hallmark of transmissible spongiform encephalopathies. It occurs when a misfolded prion protein contacts the cellular PrP. Among the molecular partners suggested to be involved in the misfolding process, the glycosaminoglycans seem to be good candidates. The present study was aimed to examine a possible link between PrP conversion efficiency and transcript level of Chst8 gene that encodes the carbohydrate N-acetylgalactosamine 4-O sulfotransferase 8. Mov cells expressing ovine PrP were transfected with shRNA directed against Chst8 transcripts. Resulting clones were characterized for their Chst8 and Prnp transcript levels, and for their content in sulfated glycosaminoglycans, more particularly sulfated chondroitins. Unexpectedly, the decreased amount of Chst8 transcript induced an increase of the chondroitin sulfate percentage among total GAGs, with an increased amount of 4-O-sulfation of GalNAc residues. Upon to infection by a sheep prion, a slight amount of PrP(Sc) was observed, which rapidly disappeared upon subpassaging. Together, these findings indicate that the Chst8 transcript level affects the glycosaminoglycan environment of the cellular prion protein, and as a consequence its ability for conversion into PrP(Sc). PMID- 21982772 TI - Role of the p21-activated kinases (PAKs) in influenza A virus replication. AB - Influenza A virus infection stimulates a wide range of virus-supportive or antiviral mechanisms in host cells. p21-Activated kinase 1 (PAK1) is a serine/threonine kinase that regulates a number of fundamental cellular processes and has been implicated in the modulation of virus replication. Here, we investigated the role of PAK1 activation during influenza A virus infection and found that virus propagation corresponded to stimulated PAK1 phosphorylation. Moreover, transfection of the active form of PAK1 (PAK1-T423E) in A549 cells induced higher viral titers (~10-fold differences) compared to that in the control vector or inactive PAK1 (PAK1-K299R)-transfected cells. PAK1-specific siRNA knockdown also resulted in 10-100-fold reductions in virus yields compared to that in the control siRNA-treatment (p<0.05). We further showed that treatment with PAK18, a PAK1 peptide inhibitor, resulted in marked suppression of both ERK 1/2 phosphorylation and infectious virus production, which was comparable to that by U0126, a specific MEK/ERK inhibitor. These results provide evidence for the importance of PAK1 activation during influenza virus infection and its association with ERK in regulating virus replication. The present study also implicates PAK1 as a potential therapeutic target for managing influenza virus infections. PMID- 21982771 TI - The pan-ErbB receptor tyrosine kinase inhibitor canertinib promotes apoptosis of malignant melanoma in vitro and displays anti-tumor activity in vivo. AB - The ErbB receptor family has been suggested to constitute a therapeutic target for tumor-specific treatment of malignant melanoma. Here we investigate the effect of the pan-ErbB tyrosine kinase inhibitor canertinib on cell growth and survival in human melanoma cells in vitro and in vivo. Canertinib significantly inhibited growth of cultured melanoma cells, RaH3 and RaH5, in a dose-dependent manner as determined by cell counting. Half-maximum growth inhibitory dose (IC(50)) was approximately 0.8 MUM and by 5 MUM both cell lines were completely growth-arrested within 72 h of treatment. Incubation of exponentially growing RaH3 and RaH5 with 1 MUM canertinib accumulated the cells in the G(1)-phase of the cell cycle within 24h of treatment without induction of apoptosis as determined by flow cytometry. Immunoblot analysis showed that 1 MUM canertinib inhibited ErbB1-3 receptor phosphorylation with a concomitant decrease of Akt-, Erk1/2- and Stat3 activity in both cell lines. In contrast to the cytostatic effect observed at doses <= 5MUM canertinib, higher concentrations induced apoptosis as demonstrated by the Annexin V method and Western blot analysis of PARP cleavage. Furthermore, canertinib significantly inhibited growth of RaH3 and RaH5 melanoma xenografts in nude mice. Pharmacological targeting of the ErbB receptors may prove successful in the treatment of patients with metastatic melanoma. PMID- 21982773 TI - Vitamin D receptor controls expression of the anti-aging klotho gene in mouse and human renal cells. AB - Isoforms of the mammalian klotho protein serve as membrane co-receptors that regulate renal phosphate and calcium reabsorption. Phosphaturic effects of klotho are mediated in cooperation with fibroblast growth factor receptor-1 and its FGF23 ligand. The vitamin D receptor and its 1,25-dihydroxyvitamin D(3) ligand are also crucial for calcium and phosphate regulation at the kidney and participate in a feedback loop with FGF23 signaling. Herein we characterize vitamin D receptor-mediated regulation of klotho mRNA expression, including the identification of vitamin D responsive elements (VDREs) in the vicinity of both the mouse and human klotho genes. In keeping with other recent studies of vitamin D-regulated genes, multiple VDREs control klotho expression, with the most active elements located at some distance (-31 to -46 kb) from the klotho transcriptional start site. We therefore postulate that the mammalian klotho gene is up-regulated by liganded VDR via multiple remote VDREs. The phosphatemic actions of 1,25 dihydroxyvitamin D(3) are thus opposed via the combined phosphaturic effects of FGF23 and klotho, both of which are upregulated by the liganded vitamin D receptor. PMID- 21982774 TI - An invertebrate [hydroxyproline]-modified neuropeptide: further evidence for a close evolutionary relationship between insect adipokinetic hormone and mammalian gonadotropin hormone family. AB - An octapeptide of the adipokinetic hormone (AKH) peptide family is identified in the corpora cardiaca of the stink bug, Nezara viridula, by ESI-MS(N) (electrospray ionization multistage MS). This is the second AKH in N. viridula and it has a hydroxyproline residue at position 6, whereas the major AKH (known as Panbo-RPCH) has Pro as the sixth amino acid residue. The correct sequence assignment of [Hyp(6)]-Panbo-RPCH is confirmed by retention time and MS spectra of the synthetic peptide. Various extraction procedures were followed to ascertain whether the hydroxylation is an artefact of extraction, or whether it is due to a true post-translational modification at the prohormone level. The proline hydroxylation is unique for invertebrate neuropeptides, while it has been described in the vertebrate gonadotropin-releasing hormone (GnRH). The current finding is another piece of evidence that AKH and GnRH form a peptide superfamily and are closely related evolutionarily. Biologically, [Hyp(6)]-Panbo-RPCH is active in vivo as an AKH, causing hyperlipaemia in the stink bug at low doses, indicating again that it is an endogenous, mature and functional hormone in this insect species. PMID- 21982775 TI - AICAR reverses ketone body mediated insulin resistance in isolated oxidative muscle. AB - Recently it was demonstrated that the ketone body beta-hydroxybutyrate (BOH) inhibits insulin-mediated glucose transport in isolated oxidative muscle, which was associated with decreased phosphorylation of Akt/protein kinase B. The purpose of the present study was to determine if activation of AMP-dependent protein kinase by the pharmacological activator AICAR could reverse the insulin resistance induced by BOH. Isolated mouse soleus muscle was incubated in vitro in the absence or presence of 5mM BOH for ~20 h. Following prolonged incubation, insulin increased 2-deoxyglucose glucose (2-DG) uptake 3-fold, but in the presence of BOH most of the insulin response was lost (only ~30% remained). Addition of 2mM AICAR during the last 2h of prolonged incubation increased the insulin response in the presence of BOH to ~80% of the normal insulin effect on 2 DG uptake. The AICAR-mediated reversal of the insulin resistance was not associated with a restoration of the insulin effect on Akt/protein kinase B phosphorylation. However, AICAR enhanced the insulin-induced phosphorylation of the Akt substrate, AS160. In conclusion, these data demonstrate that AICAR reverses the negative effect of BOH on insulin-mediated glucose uptake and this is attributed to activation of a late step in insulin signaling. PMID- 21982776 TI - Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1beta secretion. AB - Epigallocatechin-3-gallate (EGCG), the major polyphenolic component of green tea, has been demonstrated to possess anti-inflammatory, antioxidant, anti-mutagenic and anti-carcinogenic properties. The anti-melanoma effect of EGCG has been previously suggested, but no clear mechanism of action has been established. In this study, we demonstrated that EGCG inhibits melanoma cell growth at physiological doses (0.1-1 MUM). In the search for mechanisms of EGCG-mediated melanoma cell suppression, we found that NF-kappaB was inhibited, and that reduced NF-kappaB activity was associated with decreased IL-1beta secretion from melanoma cells. Since inflammasomes are involved in IL-1beta secretion, we investigated whether IL-1beta suppression was mediated by inflammasomes, and found that EGCG treatment led to downregulation of the inflammasome component, NLRP1, and reduced caspase-1 activation. Furthermore, silencing the expression of NLRP1 abolished EGCG-induced inhibition of tumor cell proliferation both in vitro and in vivo, suggesting a key role of inflammasomes in EGCG efficacy. This paper provides a novel mechanism for EGCG-induced melanoma inhibition: inflammasome downregulation->decreased IL-1beta secretion->decreased NF-kappaB activities >decreased cell growth. In addition, it suggests inflammasomes and IL-1beta could be potential targets for future melanoma therapeutics. PMID- 21982777 TI - Index proposal and basic estimator study for quantification of oscillation of the secondary flow pattern in tortuous vessels. AB - The development of atherosclerosis has been shown to correlate with regions of low wall shear stress and seemingly reduced mass transport. The local tortuosity of the arteries and local secondary flow oscillation also seem to be negatively correlated with the local occurrence of the disease. However there is currently no tool or physiological parameter that can be measured non-invasively to assess the local oscillation of the flow. Standard Colour Doppler imaging of secondary flow patterns during the blood pulse is studied and illustrated, and the local oscillation of the secondary flow pattern is proposed as an index, which could be an indicator of the likelihood of future disease development. Preliminary results are presented using a basic estimator developed for the proof of concept in the case of swirling flow, and based on colour-coded video signals collected in different configurations. In vitro results show that there is a correspondence between the Doppler patterns and the secondary flow patterns, the repeatability of the measures, and that the proposed index and its estimator reflect a joint influence of the local oscillation of the secondary flow pattern and of the flow rate. On another hand, while in vivo results still suffer from instabilities, noise and from scanners and processing limitations, they demonstrate that it is possible to use Colour Doppler imaging to image and characterize in vivo the secondary flow patterns and their oscillations non-invasively, and that it is possible for a trained clinician to perform manually such Doppler measurements for processing. PMID- 21982779 TI - Leigh syndrome caused by a novel m.4296G>A mutation in mitochondrial tRNA isoleucine. AB - Leigh syndrome is a severe neurodegenerative disease with heterogeneous genetic etiology. We report a novel m.4296G>A variant in the mitochondrial tRNA isoleucine gene in a child with Leigh syndrome, mitochondrial proliferation, lactic acidosis, and abnormal respiratory chain enzymology. The variant is present at >75% heteroplasmy in blood and cultured fibroblasts from the proband, <5% in asymptomatic maternal relatives, and is absent in 3000 controls. It is located in the highly conserved anticodon region of tRNA(Ile) where three other pathogenic changes have been described. We conclude that there is strong evidence to classify m.4296G>A as a pathogenic mutation causing Leigh syndrome. PMID- 21982778 TI - Visualization and quantification of cardiac mitochondrial protein clusters with STED microscopy. AB - The visualization and quantification of mitochondria-associated proteins with high power microscopy methods is of particular interest to investigate protein architecture in this organelle. We report the usage of a custom-made STimulated Emission Depletion (STED) fluorescence nanoscope with ~30nm lateral resolution for protein mapping of Percoll-purified viable mitochondria from murine heart. Using this approach, we were able to quantify and resolve distinct protein clusters within mitochondria; specifically, cytochrome c oxidase subunit 2 is distributed in clusters of ~28nm; whereas the voltage dependent anion channel 1 displays three size distributions of ~33, ~55 and ~83nm. PMID- 21982780 TI - [Effectiveness of a supportive care form for family physicians]. AB - To assess the effectiveness of a standardized form in altering family physicians knowledge regarding supportive care delivered to their patients. We conducted an uncontrolled before and after study involving 42 cancer patients who were provided with supportive care at hospital. During the intervention study period, a standardized form was sent to their family physician within 1 week of discharge. The use of the standardized form was associated with an increase in the percentages of correct answers regarding consultations with psychologists (95% versus 19%, P < 0.001), social workers (95% versus 14%, P < 0.001), nutritionists (86% versus 9%, P < 0.001), and palliative care physicians (90% versus 52 %, P = 0.006). Yet, the percentages of correct answers regarding discharge arrangements did not differ between the two study groups. The use of a standardized form improves family physician information regarding supportive care delivered to their patients during hospital course but does not alter information on discharge arrangements and follow-up. PMID- 21982781 TI - Crystallizing membrane proteins using lipidic bicelles. AB - Crystallization of membrane proteins remains a significant challenge. For proteins resistant to the traditional approach of directly crystallizing from detergents, lipidic phase crystallization can be a powerful tool. Bicelles are an excellent medium for crystallizing membrane proteins in a lipidic environment. They can be described as bilayer discs formed by the mixture of a long-chain phospholipid and an amphiphile in an aqueous medium. Membrane proteins can be readily reconstituted into bicelles, where they are maintained in a native-like bilayer environment. Importantly, membrane proteins have been shown to be fully functional in bicelles under physiological conditions. Protein-bicelle mixtures can be manipulated with almost the same ease as detergent-solubilized membrane proteins, making bicelles compatible with standard equipment including high throughput crystallization robots. A number of membrane proteins have now been successfully crystallized using the bicelle method, including bacteriorhodopsin, beta2 adrenergic receptor, voltage-dependent anion channel, xanthorhodopsin and rhomboid protease. Because of the success with a variety of membrane proteins and the ease of implementation, bicelles should be a part of every membrane protein crystallographer's arsenal. PMID- 21982782 TI - Profiling of integral membrane proteins and their post translational modifications using high-resolution mass spectrometry. AB - Integral membrane proteins pose challenges to traditional proteomics approaches due to unique physicochemical properties including hydrophobic transmembrane domains that limit solubility in aqueous solvents. A well resolved intact protein molecular mass profile defines a protein's native covalent state including post translational modifications, and is thus a vital measurement toward full structure determination. Both soluble loop regions and transmembrane regions potentially contain post-translational modifications that must be characterized if the covalent primary structure of a membrane protein is to be defined. This goal has been achieved using electrospray-ionization mass spectrometry (ESI-MS) with low-resolution mass analyzers for intact protein profiling, and high resolution instruments for top-down experiments, toward complete covalent primary structure information. In top-down, the intact protein profile is supplemented by gas-phase fragmentation of the intact protein, including its transmembrane regions, using collisionally activated and/or electron-capture dissociation (CAD/ECD) to yield sequence-dependent high-resolution MS information. Dedicated liquid chromatography systems with aqueous/organic solvent mixtures were developed allowing us to demonstrate that polytopic integral membrane proteins are amenable to ESI-MS analysis, including top-down measurements. Covalent post translational modifications are localized regardless of their position in transmembrane domains. Top-down measurements provide a more detail oriented high resolution description of post-transcriptional and post-translational diversity for enhanced understanding beyond genomic translation. PMID- 21982783 TI - Neuropathology of the area postrema in sudden intrauterine and infant death syndromes related to tobacco smoke exposure. AB - The area postrema is a densely vascularized small protuberance at the inferoposterior limit of the fourth ventricle, outside of the blood-brain barrier. This structure, besides to induce emetic reflex in the presence of noxious chemical stimulation, has a multifunctional integrative capacity to send major and minor efferents to a variety of brain centers particularly involved in autonomic control of the cardiovascular and respiratory activities. In this study we aimed to focus on the area postrema, which is so far little studied in humans, in a large sample of subjects aged from 25 gestational weeks to 10 postnatal months, who died of unknown (sudden unexplained perinatal and infant deaths) and known causes (controls). Besides we investigated a possible link between alterations of this structure, sudden unexplained fetal and infant deaths and maternal smoking. By the application of morphological and immunohistochemical methods, we observed a significantly high incidence of alterations of the area postrema in fetal and infant victims of sudden death as compared with age-matched controls. These pathological findings, including hypoplasia, lack of vascularization, cystic formations and reactive gliosis, were related to maternal smoking. We hypothesize that components from maternal cigarette smoke, particularly in pregnancy, could affect neurons of the area postrema connected with specific nervous centers involved in the control of vital functions. In conclusion, we suggest that the area postrema should be in depth examined particularly in victims of sudden fetal or infant death with smoker mothers. PMID- 21982784 TI - WITHDRAWN: Effect of blood glucose fluctuation on the function of rat pancreatic islets in vivo. AB - This article has been withdrawn at the request of the authors. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 21982785 TI - Neutral aminopeptidase and dipeptidyl peptidase IV in the development of collagen II-induced arthritis. AB - This study evaluated the hypothesis that neutral (APN) and dipeptidyl-IV (DPPIV) aminopeptidase activity levels would be critical for the susceptibility to arthritis in collagen-induced model (CIA). The macroscopic signs of arthritis in CIA rats were checked and peripheral blood, synovial fluid and synovial tissue from knee joint were withdrawn. Soluble (SF) and solubilized membrane-bound (MF) fractions from the synovial tissue and peripheral blood mononuclear cells (PBMCs) were obtained. APN and DPPIV activities were fluorometrically quantified. Severe swelling in both the entire hind paws was the minimum criterion to select CIA rats with arthritis. These arthritic rats had high APN in plasma, synovial fluid and SF of the synovial tissue, together with low APN and DPPIV in MF of PBMCs and hallmark histological changes in tibio-tarsal joint. CIA rats with no macroscopic signs of arthritis were diagnosed as resistant and they had low APN in MF of the synovial tissue, low DPPIV in SF of PBMCs and high DPPIV in plasma together with histological aspects of tibio-tarsal joint similar to healthy control rats. Data suggested that APN and DPPIV activity levels are related to the development of arthritis, being protective or inducer of the susceptibility. Understanding what is controlling the compartment-specific changes of these peptidases and looking at ways in which to manipulate their activities may lead to a better knowledge of the arthritic processes and novel treatments. PMID- 21982786 TI - Contributions of trunk muscles to anticipatory postural control in children with and without developmental coordination disorder. AB - Current evidence suggests that movement quality is impacted by postural adjustments made in advance of planned movement. The trunk inevitably plays a key role in these adjustments, by creating a stable foundation for limb movement. The purpose of this study was to examine anticipatory trunk muscle activity during functional tasks in children with and without developmental coordination disorder (DCD). Eleven children with DCD (age 7 to 14 years) and 11 age-matched, typically developing children performed three tasks: kicking a ball, climbing stairs, and single leg balance. Surface electromyography (EMG) was used to examine the neuromuscular activity of bilateral transversus abdominis/internal oblique, external oblique and L3/4 erector spinae, as well as the right tibialis anterior and rectus femoris muscles. Onset latencies for each muscle were calculated relative to the onset of rectus femoris activity. In comparison to the children with DCD, the typically-developing children demonstrated earlier onsets for right tibialis anterior, bilateral external oblique, and right transversus abdominis/internal oblique muscles. These results suggest that anticipatory postural adjustments may be associated with movement problems in children with DCD, and that timing of both proximal and distal muscles should be considered when designing intervention programs for children with DCD. PMID- 21982787 TI - Energy redistribution analysis of dynamic mechanisms of multi-body, multi-joint kinetic chain movement during soccer instep kicks. AB - The purpose of this study is to develop a model to analyze energy redistribution mechanisms of a multi-joint limb system and to examine the mechanisms underlying the production of the mechanical energy of the system during instep kicking. Kicking movements of 11 collegiate soccer players were recorded using a motion capture system, and ground reaction force during kicks was measured. Using the experimental data and the state-space power analysis developed in the current study, the kinetic energy change of the modeled segments was decomposed into causal components due to various dynamic factors (muscular and non-muscular interactive moments). The results showed that the increase of the kinetic energy of the kicking limb resulted from the energy transfer mechanisms between the decelerated segment (a proximal segment) and accelerated segment (a distal segment), induced by a non-muscular interactive moment due to the external joint force or the centrifugal force. The proximal (thigh) to distal (shank) sequential motion pattern observed was due to the energy transfer mechanism induced by the centrifugal effect acting to accelerate the shank and decelerate the thigh. The fact suggests that effective use of that mechanism may be advantageous to enhance the kinetic energy of the kicking shank. In conclusion, energy transfer mechanisms likely play a greater role in dynamic kicking than muscle power output, and better coordination to exchange kinetic energy among segments makes kicking more efficient. PMID- 21982788 TI - Furfuran lignans and a flavone from Artemisia gorgonum Webb and their in vitro activity against Plasmodium falciparum. AB - The chemical composition of the aerial parts of the Cape Verdean endemic shrub Artemisia gorgonum Webb (Asteraceae) was careful investigated, which led to the isolation and identification of six known furfuran lignans: eudesmin (1), magnolin (2), epimagnolin A (3), aschantin (4), kobusin (5), sesamin (6) and a flavone: artemetin (7). Compounds 1-7 were evaluated in vitro for their cytotoxicity in a screening panel consisting of various mammalian tumor cell lines, for their antimalarial activity against chloroquine-resistant Plasmodium falciparum (FcB1 strain) and for their cytotoxicity against murine normal cells (CFU-GM). While no promising cytotoxicity against human tumor cells were noticed, marginal potency and selectivity was found for compounds 1-5 against murine colon 38. Besides, compounds 2-7 showed mild antiplasmodial activities, 6 and 7 being the most active compounds (IC(50) 3.37 and 3.50 MUg/ml respectively) without noticeable toxicity on mammalian normal cells. This is the first report of antiplasmodial activity for furfuran lignans and the first isolation of 1-7 from Artemisia gorgonum. PMID- 21982789 TI - Commentary: Regression residual vs. Bayesian analysis of medicinal floras. PMID- 21982790 TI - Statistical tools in ethnopharmacology. PMID- 21982791 TI - Protective effect of Shenfu injection on thromboangiitis obliterans model rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Thromboangiitis obliterans (TAO) or Buerger's disease is a non atherosclerotic, segmentar inflammatory vasculitis that is incurable at present. Shenfu injection (SFI), a traditional Chinese formulation, have been confirmed to produce protective influences on several organs and limb during ischemia and reperfusion (IR) injury in rats. However, the effects of SFI on TAO remain unclear. MATERIALS AND METHODS: Adult male Sprague Dawley rats were randomly divided into sham operated group, TAO model group, SFI 2.5mg/kg (low dose), 5mg/kg (medium dose) and 10mg/kg (high dose) groups (n=8). Rats were intravenously administered SFI 2.5, 5 and 10mg/kg or saline once per day for 15 days. TAO model was prepared by injecting sodium laurate into the femoral artery of rats. Then we examined the changes of pathological signs, pathologic grading of thrombus, the indexes of hematology, the contents of thromboxane B2 (TXB2), 6 keto-prostaglandin F(lalpha) (6-K-PGF(1alpha)) in plasma following SFI or saline treatment. RESULTS: More pathological signs of lesions, higher grades of pathological thrombosis, increased blood platelet counts, the increase in the TXB2 and TXB2/6-K-PGF(1alpha) ratio, as well as the decrease of 6-K-PGF(1alpha) in TAO model group were shown in present experiments; SFI treatment significantly improved the pathological signs of lesions induced by sodium laurate injection, reduced the numbers of thrombus formation, blood platelet counts, the TXB2 and TXB2/6-K-PGF(1alpha) ratio but increased the 6-K-PGF(1alpha) compared with TAO model group. However, there were no significant alterations in the counts of red blood cell, leucocyte and neutrophil among these groups. CONCLUSIONS: Our preliminary findings first indicated that SFI can produce significant therapeutic effects on experimental Buerger's disease model rats in a dose independent manner. The underlying mechanisms may be due to its modifying hematology, inhibiting platelet aggregation and enhancing anti-thrombotic function of vessel endothelia. PMID- 21982792 TI - Validated liquid chromatographic method and analysis of content of tilianin on several extracts obtained from Agastache mexicana and its correlation with vasorelaxant effect. AB - ETHNOPHARMACOLOGICAL RELEVANCE: To optimize the obtention of tilianin, an antihypertensive flavonoid isolated from Agastache mexicana (Lamiaceae), a medicinal plant used in Mexico for the treatment of hypertension. Also, a validated HPLC method to quantify tilianin from different extracts, obtained by several extraction methods, was developed. MATERIALS AND METHODS: The aerial parts of Agastache mexicana were dried at different temperatures (22, 40, 50, 90, 100 and 180 degrees C) and the dry material was extracted with methanol by maceration to compare the content of the active constituent tilianin in the samples. Furthermore, EtOH:H(2)O (7:3), infusion and decoction extracts were prepared from air-dried samples at room temperature to compare the content and composition of the different extraction methods. Moreover, an ex vivo vasorelaxant test on endothelium-intact aortic rat rings was conducted, in order to correlate the presence of tilianin with the activity of each extract. RESULTS: Higher concentration and amounts of tilianin were determined from chromatograms in the obtained methanolic extracts from plant material dried at 90, 50, 40 and 22 degrees C, followed by 100 degrees C; however, lower concentrations were observed in dried at 180 degrees C and EtOH:H(2)O (7:3). It is worth to notice that methanolic extracts with higher amount of tilianin were the most potent vasorelaxant extracts, even though these extracts were less potent than carbachol, a positive control used. Finally, decoction, infusion and EtOH:H(2)O (7:3) extracts did not show any vasorelaxant effect. CONCLUSION: Results suggest that extracts with higher concentration of tilianin possess the best vasorelaxant activity, which allowed us to have a HPLC method for future quality control for this medicinal plant. PMID- 21982793 TI - Phyllanthus amarus: ethnomedicinal uses, phytochemistry and pharmacology: a review. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Phyllanthus amarus Schum. & Thonn. belongs to the family Euphorbiaceae is a small herb well known for its medicinal properties and widely used worldwide. P. amarus is an important plant of Indian Ayurvedic system of medicine which is used in the problems of stomach, genitourinary system, liver, kidney and spleen. It is bitter, astringent, stomachic, diuretic, febrifuge and antiseptic. The whole plant is used in gonorrhea, menorrhagia and other genital affections. It is useful in gastropathy, diarrhoea, dysentery, intermittent fevers, ophthalmopathy, scabies, ulcers and wounds. MATERIALS AND METHODS: The present review covers a literature across from 1980 to 2011. Some information collected from traditional Ayurvedic texts and published literature on ethanomedicinal uses of Phyllanthus amarus in different countries worldwide. RESULTS: Phytochemical studies have shown the presence of many valuable compounds such as lignans, flavonoids, hydrolysable tannins (ellagitannins), polyphenols, triterpenes, sterols and alkaloids. The extracts and the compounds isolated from P. amarus show a wide spectrum of pharmacological activities including antiviral, antibacterial, antiplasmodial, anti-inflammatory, antimalarial, antimicrobial, anticancer, antidiabetic, hypolipidemic, antioxidant, hepatoprotective nephroprotective and diurectic properties. CONCLUSION: The present review summarizes information concerning the morphology, ecology, ethnopharmacology, phytochemistry, biological activities, clinical applications and toxicological reports of P. amarus. This review aims at gathering the research work undertaken till date on this plant in order to provide sufficient baseline information for future works and commercial exploitation. PMID- 21982794 TI - Synthesis and anticonvulsant activity of trans- and cis-2-(2,6-dimethylphenoxy)-N (2- or 4-hydroxycyclohexyl)acetamides and their amine analogs. AB - A group of trans- and cis-2-(2,6-dimethylphenoxy)-N-(2 hydroxycyclohexyl)acetamides (1-7) and -ethylamines (8-9) have been synthesized and investigated for their anticonvulsant activity. One of them, racemic trans-2 (2,6-dimethylphenoxy)-N-(2-hydroxycyclohexyl)acetamide proved to be the most effective in MES (mice, ip), exhibiting ED(50)=42.97 mg/kg b.w. and TD(50)=105.67 mg/kg b.w. It also proved protection in focal seizures (electric kindling, rats, ip) and it raises seizure threshold. The mechanism of action is inhibition of voltage-gated sodium currents and enhancement of GABA effect. Safety pharmacology assay on threshold tonic extension revealed no lowering of the seizure threshold. PMID- 21982795 TI - Discovery of new orally active prostaglandin D2 receptor antagonists. AB - To identify an orally available drug candidate, a series of 3 benzoylaminophenylacetic acids were synthesized and evaluated as prostaglandin D(2) (PGD(2)) receptor antagonists. Some of the compounds tested were found to exhibit excellent inhibitory activity against cAMP accumulation in human platelet rich plasma (hPRP), which is one of the indexes of DP antagonism. The optimization process including improvement of the physicochemical properties such as solubility, which may result in an improved pharmacokinetic (PK) profile, is presented. Optimized compounds were studied for their pharmacokinetics and in vivo potential. A structure-activity relationship study is also presented. Some of the test compounds were found to have in vivo efficacy towards the inhibition of PGD(2)-induced and OVA-induced vascular permeability in guinea pig conjunctiva. PMID- 21982796 TI - Design, synthesis and biological evaluation of 6-pyridylmethylaminopurines as CDK inhibitors. AB - The cyclin-dependent kinase (CDK) inhibitor seliciclib (1, CYC202) is in phase II clinical development for the treatment of cancer. Here we describe the synthesis of novel purines with greater solubility, lower metabolic clearance, and enhanced potency versus CDKs. These compounds exhibit novel selectivity profiles versus CDK isoforms. Compound alphaSbetaR-21 inhibits CDK2/cyclin E with IC(50)=30 nM, CDK7-cyclin H with IC(50)=1.3 MUM, and CDK9-cyclinT with IC(50)=0.11 MUM; it (CCT68127) inhibits growth of HCT116 colon cancer cells in vitro with GI(50)=0.7 MUM; and shows antitumour activity when dosed p.o. at 50mg/kg to mice bearing HCT116 solid human tumour xenografts. PMID- 21982797 TI - 9,10-secosteroids, protein kinase inhibitors from the Chinese gorgonian Astrogorgia sp. AB - Fourteen new 9,10-secosteroids designated as astrogorgols A-N (1-14) were isolated from a Chinese gorgonian Astrogorgia sp. together with eight known analogues. The structural patterns were characterized by the presence of a sterol based 9,10-seco nucleus containing a 3-hydroxy-10-methylphenyl ring. Astrogorgol N (14) possessing a 1,4-dien-3-one unit in ring A was biogenetically considered as an intermediate to generate diverse 9,10-secosteroids. Five compounds showed significant inhibitory activities against human tumor related protein kinases, including ALK, AXL, FAK, IGF-1R, MET wt, SRC, and VEGF-R2. PMID- 21982798 TI - Genetic diversity in the merozoite surface protein 1 and 2 genes of Plasmodium falciparum from the Artibonite Valley of Haiti. AB - Describing genetic diversity of the Plasmodium falciparum parasite provides important information about the local epidemiology of malaria. In this study, we examined the genetic diversity of P. falciparum isolates from the Artibonite Valley in Haiti using the allelic families of merozoite surface protein 1 and 2 genes (msp-1 and msp-2). The majority of study subjects infected with P. falciparum had a single parasite genotype (56% for msp-1 and 69% for msp-2: n=79); 9 distinct msp-1 genotypes were identified by size differences on agarose gels. K1 was the most polymorphic allelic family with 5 genotypes (amplicons from 100 to 300 base pairs [bp]); RO33 was the least polymorphic, with a single genotype (120-bp). Although both msp-2 alleles (3D7/IC1, FC27) had similar number of genotypes (n=4), 3D7/IC1 was more frequent (85% vs. 26%). All samples were screened for the presence of the K76T mutation on the P. falciparum chloroquine resistance transporter (pfcrt) gene with 10 of 79 samples positive. Of the 2 (out of 10) samples from individuals follow-up for 21 days, P. falciparum parasites were present through day 7 after treatment with chloroquine. No parasites were found on day 21. Our results suggest that the level of genetic diversity is low in this area of Haiti, which is consistent with an area of low transmission. PMID- 21982799 TI - Regulation of matrix metalloproteinases activity studied in human endometrium as a paradigm of cyclic tissue breakdown and regeneration. AB - When abundant and activated, matrix metalloproteinases (MMPs, or matrixins) degrade most, if not all, constituents of the extracellular matrix (ECM). The resulting massive tissue breakdown is best exemplified in humans by the menstrual lysis and shedding of the endometrium, the mucosa lining the uterus. After menstruation, MMP activity needs to be tightly controlled as the endometrium regenerates and differentiates to avoid abnormal tissue breakdown while allowing tissue repair and fine remodelling to accommodate implantation of a blastocyst. This paper reviews how MMPs are massively present and activated in the endometrium at menstruation, and how their activity is tightly controlled at other phases of the cycle. Progesterone represses expression of many but not all MMPs. Its withdrawal triggers focal expression of MMPs specifically in the areas undergoing lysis, an effect mediated by local cytokines such as interleukin 1alpha, LEFTY-2, tumour necrosis factor-alpha and others. MMP-3 is selectively expressed at that time and activates proMMP-9, otherwise present in latent form throughout the cycle. In addition, a large number of neutrophils loaded with MMPs are recruited at menstruation through induction of chemokines, such as interleukin-8. At the secretory phase, progesterone repression of MMPs is mediated by transforming growth factor-beta. Tissue inhibitors of metalloproteinases (TIMPs) are abundant at all phases of the cycle to prevent any undue MMP activity, but are likely overwhelmed at menstruation. At other phases of the cycle, MMPs can elude TIMP inhibition as exemplified by recruitment of active MMP-7 to the plasma membrane of epithelial cells, allowing processing of membrane-associated growth factors needed for epithelial repair and proliferation. Finally, receptor-mediated endocytosis through low density lipoprotein receptor-related protein-1 (LRP-1) efficiently clears MMP-2 and -9 at the proliferative and secretory phases. This mechanism is probably essential to prevent any excessive ECM degradation by the active form of MMP-2 that is permanently present. However, shedding of the ectodomain of LRP-1 specifically at menstruation prevents endocytosis of MMPs allowing full degradation of the ECM. Thus endometrial MMPs are regulated at the levels of transcription, release from infiltrating neutrophils, activation, binding to the cell membrane, inhibition by TIMPs and endocytic clearance by LRP-1. This allows tight control during endometrial growth and differentiation but results in a burst of activity for menstrual tissue breakdown. This article is part of a Special Issue entitled: Proteolysis 50 years after the discovery of lysosome. PMID- 21982800 TI - The polymorphisms of P53 codon 72 and MDM2 SNP309 and renal cell carcinoma risk in a low arsenic exposure area. AB - Our recent study demonstrated the increased risk of renal cell carcinoma (RCC) associated with high urinary total arsenic levels among people living in a low arsenic exposure area. Genomic instability is important in arsenic carcinogenesis. This study evaluated the relationship between the polymorphisms of p53, p21, and MDM2, which plays a role in gene stability, and the arsenic related RCC risk. Here, we found that p53 Pro/Pro genotype and MDM2 SNP309 GG genotype significantly increased RCC risk compared to the p53 Arg/Arg genotype and MDM2 SNP309 TT genotype. RCC patients with the p53Arg/Arg genotype had a signicantly low percentage of inorganic arsenic, a low percentage of monomethylarsonic acid (MMA), and a high percentage of dimethylarsinic acid (DMA), which indicates efcient arsenic methylation capacity. Subjects with the p53 Arg/Pro + Pro/Pro genotype or MDM2 SNP309 TG+GG genotype, in conjunction with high urinary total arsenic (>=14.02MUg/L), had a signicantly higher RCC risk than those with the p53 Arg/Arg or MDM2 SNP309 TT genotypes and low urinary total arsenic. Taken together, this is the first study to show that a variant genotype of p53 Arg(72)Pro or MDM2 SNP309 may modify the arsenic-related RCC risk even in a non-obvious arsenic exposure area. PMID- 21982801 TI - D-saccharic acid-1,4-lactone ameliorates alloxan-induced diabetes mellitus and oxidative stress in rats through inhibiting pancreatic beta-cells from apoptosis via mitochondrial dependent pathway. AB - Oxidative stress plays a vital role in diabetic complications. To suppress the oxidative stress mediated damage in diabetic pathophysiology, a special focus has been given on naturally occurring antioxidants present in normal diet. D saccharic acid 1,4-lactone (DSL), a derivative of D-glucaric acid, is present in many dietary plants and is known for its detoxifying and antioxidant properties. The aim of the present study was to evaluate the beneficial role of DSL against alloxan (ALX) induced diabetes in the pancreas tissue of Swiss albino rats. A dose-dependent study for DSL (20-120 mg/kg body weight) was carried out to find the effective dose of the compound in ALX-induced diabetic rats. ALX exposure elevated the blood glucose, glycosylated Hb, decreased the plasma insulin and disturbed the intra-cellular antioxidant machineries whereas oral administration of DSL at a dose of 80 mg/kg body weight restored these alterations close to normal. Investigating the mechanism of the protective activity of DSL we observed that it prevented the pancreatic beta-cell apoptosis via mitochondria-dependent pathway. Results showed decreased mitochondrial membrane potential, enhanced cytochrome c release in the cytosol and reciprocal regulation of Bcl-2 family proteins in the diabetic rats. These events were also found to be associated with increased level of Apaf-1, caspase 9, and caspase 3 that ultimately led to pancreatic beta-cell apoptosis. DSL treatment, however, counteracted these changes. In conclusion, DSL possesses the capability of ameliorating the oxidative stress in ALX-induced diabetes and thus could be a promising approach in lessening diabetic complications. PMID- 21982802 TI - A new mechanism of action of a C2 domain-derived novel PKC inhibitor peptide. AB - Novel protein kinase Cs (nPKCs) contain an N-terminal C2 domain that cannot bind to calcium. We have previously shown that the Aplysia novel PKC Apl II's C2 domain inhibits binding of diacylglycerol (DAG) to the C1 domain and that this inhibition is removed by phosphatidic acid (PA) binding to the C1b domain. Another model for C2 domain regulation of nPKCs suggests that the C2 domain binds to receptors for activated C kinase (RACKs) to assist in kinase translocation and activation. In the present study, we examined how a pharmacological peptide derived from RACK-binding site in the vertebrate novel PKCE regulates translocation of PKC Apl II from the cytosol to the plasma membrane. We found that a C2 domain-derived inhibitor peptide inhibited PKC Apl II translocation. This inhibition was removed by R273H mutation in the C1b domain and by phosphatidic acid, which can both remove C2-domain mediated inhibition suggesting that the peptide can regulate C1-C2 domain interactions. PMID- 21982803 TI - Impaired P2X and P2Y receptor-mediated signaling in HPRT-deficient B103 neuroblastoma cells. AB - Defect of hypoxanthine phosphoribosyl transferase (HPRT) causes Lesch-Nyhan disease (LND), but the link between HPRT deficiency and the self-injurious behavior of LND is unknown. In a previous study (Pinto et al., J. Neurochem. 72 (2005) 1579-1586) we reported on a decrease in nucleotidase activity in membranes of several HPRT(-) cell lines and fibroblasts from LND patients. Since nucleotidases are involved in ATP-induced signal transduction, in the present study, we tested the hypothesis that P2X and P2Y receptor-mediated signal transduction is impaired in HPRT deficiency. As model we studied rat B103 neuroblastoma cells. Compared to control cells, in HPRT(-) cells, NTP and NDP induced Ca(2+) influx across the membrane and Ca(2+) mobilization from intracellular stores were impaired. Both P2X and P2Y receptors were involved in the responses. Quantitative real-time PCR revealed reduced expression of receptors P2X(3), P2X(5), P2Y(2), P2Y(4), P2Y(12), P2Y(13) and P2Y(14) in HPRT deficiency. Collectively, HPRT deficiency is associated with abnormal purinergic signaling, encompassing P2X and P2Y receptors and nucleotidases. PMID- 21982804 TI - The involvement of down-regulation of Cdh1-APC in hippocampal neuronal apoptosis after global cerebral ischemia in rat. AB - Anaphase-promoting complex (APC) and its coactivator Cdh1 are required for maintaining cells in G1 phase of cell cycle in proliferating cells. Recent studies showed that Cdh1-APC was active in post-mitotic neurons, which regulates neuronal survival, differentiation, axonal growth and synaptic development. However, the possible function of Cdh1-APC in ischemic brain injury has not been determined. This study aimed to investigate changes in the activity of Cdh1-APC in hippocampus after global cerebral ischemia in rat. We found that, compared with sham group, the expression of Cdh1 in hippocampus was significantly decreased on 1 and 3 days of reperfusion in ischemia group (P<0.05), while neuronal apoptosis were found in hippocampal CA1 region and the two downstream substrates of Cdh1-APC (SnoN and Skp2) were significantly increased after global cerebral ischemia (P<0.05). This study demonstrates that the down-regulation of Cdh1-APC is associated with neuronal apoptosis in hippocampus following global cerebral ischemia. It brings a prospect to explore the further function of Cdh1 APC in the injured nervous system. PMID- 21982805 TI - Effect of acupuncture on naloxone-precipitated withdrawal syndrome in morphine experienced rats: the mediation of GABA receptors. AB - Repeated morphine administration increases extracellular dopamine levels in the nucleus accumbens, which results in behavioral sensitization that can be suppressed by acupuncture at Shenmen (HT7) points. The present study was conducted to investigate the effects of acupuncture at HT7 on morphine withdrawal syndrome as well as to explore the role of GABA receptors in mediating the effects of HT7 acupuncture. We induced morphine withdrawal by injecting naloxone to rats that self-administer morphine and evaluated the effects of acupuncture and/or GABA receptor antagonists on their withdrawal symptoms. Acupuncture at HT7, but not at the control point LI5, significantly decreased symptoms of morphine withdrawal. HT7 inhibition of the withdrawal syndrome was blocked by pretreatment with either the GABA(A) receptor antagonist bicuculline or the GABA(B) antagonist SCH 50911. These findings suggest that the effects of acupuncture on suppression of morphine withdrawal syndrome are mediated, at least in part, through GABA receptors. PMID- 21982806 TI - SKF 83566 attenuates the effects of ghrelin on performance in the object location memory task. AB - Increasing research implicates ghrelin, a metabolic signaling peptide, in memory processes including acquisition, consolidation, and retention. The present study investigated the effects of ghrelin on spatial memory acquisition by utilizing the object location memory task paradigm. Given the co-expression of ghrelin and dopamine D(1) receptors within hippocampal neurons, we examined a potential interaction between these two systems on memory performance. When injected into the dorsal third ventricle (D3V) of male Sprague-Dawley rats, proximal to hippocampal tissue, ghrelin (500 pmol) increased the amount of time spent with objects in novel locations. This effect was completely reversed by the D(1) antagonist SKF 83566 (100 MUg/kg IP), although when administered alone, the antagonist had no effect on task performance (10-100 MUg/kg). We also examined the feeding effects of D3V ghrelin and found that the peptide reliably increased food intake (500 pmol) but that this effect was not blocked by SKF 83566 (100 MUg/kg). When given alone, SKF 83566 did not alter food intake (10-100 MUg/kg). Our findings indicate that, in addition to an orexigenic effect, ghrelin improves acquisition of spatial location memories. Furthermore, D(1) receptor activation is necessary for ghrelin to improve the encoding of spatial memories but does not impact the increase in food intake elicited by the peptide. PMID- 21982807 TI - Intracerebroventricular injection of human prostatic acid phosphatase has potent neuroprotective effects against transient focal cerebral ischemia in rats. AB - Though the potential use of adenosine as a neuroprotective agent has long been realized, there are currently no adenosine-based therapies for the prevention or treatment of cerebral ischemia and reperfusion injury. Prostatic acid phosphatase (PAP), an enzyme that has long served as a diagnostic marker for prostate cancer, has been recently demonstrated to exhibit ecto-5'-nucleotidase activity, and dephosphorylate endogenous extracellular AMP to adenosine. We therefore tested the hypothesis that PAP has sustained and potent neuroprotective effects against cerebral ischemia in the rat model of middle cerebral artery occlusion. We found that hPAP produced significant neuroprotection against focal cerebral ischemia, as evident from significant reduction in cerebral infarction and neurological deficits. The therapeutic time window for hPAP in rat focal cerebral ischemia model was limited from 6 h before ischemia to 1.5 h after reperfusion. The present study suggested that PAP is a potential candidate for the prevention and treatment of cerebral ischemic injury, especially during perioperative period. PMID- 21982808 TI - The effects of instruction and hand dominance on grip-to-load force coordination in manipulation tasks. AB - The force applied upon a vertically oriented hand-held object could be decomposed into two orthogonal and highly coordinated components: the grip force (GF; the component perpendicular to the hand-object contact area that provides friction) and the load force (LF; the parallel component that can move the object or support the body). The aim of this study was to investigate the underexplored effects of task instruction and hand dominance on GF-LF coordination. Sixteen right-handed subjects performed bimanual manipulation against a horizontally oriented instrumented device under different sets of instructions. The tasks involved exertion of ramp-and-hold or oscillation patterns of LF performed symmetrically with two hands, while the instructions regarding individual actions were either similar (pull with both hands) or dissimilar (pull with one hand and hold with another). The results revealed that the instruction "to pull" leads to higher indices of GF-LF coordination than the instruction "to hold", as evidenced by a lower GF-LF ratio, higher GF-LF coupling, and higher GF modulation. The only effect of hand dominance was a moderate time lag of GF relative to LF changes observed in the non-dominant hand. We conclude that the instructions could play an important role in GF-LF coordination and, therefore, they should be taken into account when exploring or routinely testing hand function. Additionally, the results suggest that the neural control of GF of the non-dominant hand could involve some feedback mechanisms. PMID- 21982809 TI - 5HT(1A) and 5HT(1B) receptors of medial prefrontal cortex modulate anxiogenic like behaviors in rats. AB - Medial prefrontal cortex (MPFC) is one of the brain regions which play an important role in emotional behaviors. The purpose of the present study was to evaluate the role of 5HT(1A) and 5HT(1B) receptors of the MPFC in modulation of anxiety behaviors in rats. The elevated plus maze (EPM) which is a useful test to investigate the effects of anxiogenic or anxiolytic drugs in rodents, was used. Bilateral intra-MPFC administration of 5HT(1A) receptor agonist, 8-OH-DPAT (5, 10, and 50 ng/rat) decreased the percentages of open arm time (OAT%) and open arm entries (OAE%), indicating an anxiogenic response. Moreover, administration of 5HT(1A) receptor antagonist, NAN-190 (0.25, 0.5, and 1 MUg/rat) significantly increased OAT% and OAE%. Pre-treatment administration of NAN-190 (0.5 MUg/rat), which was injected into the MPFC, reversed the anxiogenic effects of 8-OH-DPAT (5, 10, and 50 ng/rat). Intra-MPFC microinjection of 5HT(1B) receptor agonist, CGS-12066A (0.25, 0.5, and 1 MUg/rat) significantly decreased OAT% and OAE%, without any change in locomotor activity, indicating an anxiogenic effect. However, injection of 5HT(1B) receptor antagonist, SB-224289 (0.5, 1, and 2 MUg/rat) into the MPFC showed no significant effect. In conclusion, these findings suggest that 5HT(1A) and 5HT(1B) receptors of the MPFC region modulate anxiogenic-like behaviors in rats. PMID- 21982810 TI - Will shared decision making between patients with chronic musculoskeletal pain and physiotherapists, osteopaths and chiropractors improve patient care? AB - BACKGROUND: Chronic musculoskeletal pain (CMP) is treated in primary care by a wide range of health professionals including chiropractors, osteopaths and physiotherapists. AIMS: To explore patients and chiropractors, osteopaths and physiotherapists' beliefs about CMP and its treatment and how these beliefs influenced care seeking and ultimately the process of care. METHODS: Depth interviews with a purposive sample of 13 CMP patients and 19 primary care health professionals (5 osteopaths, 4 chiropractors and 10 physiotherapists). RESULTS: Patients' models of their CMP evolved throughout the course of their condition. Health professionals' models also evolved throughout the course of their treatment of patients. A key influence on patients' consulting behaviour appeared to be finding someone who would legitimate their suffering and their condition. Health professionals also recognized patients' need for legitimation but often found that attempts to explore psychological factors, which may be influencing their pain could be construed by patients as delegitimizing. Patients developed and tailored their consultation strategies throughout their illness career but not always in a strategic fashion. Health professionals also reflected on how patients' developing knowledge and changing beliefs altered their expectations. Therefore, overall within our analysis, we identified three themes: 'the evolving nature of patients and health professionals models of understanding CMP'; 'legitimating suffering' and 'development and tailoring of consultation and treatment strategies throughout patients' illness careers'. CONCLUSIONS: Seeking care for any condition is not static but a process particularly for long-term conditions such as CMP. This may need to be taken into account by both CMP patients and their treating health professionals, in that both should not assume that their views about causation and treatment are static and that instead they should be revisited on a regular basis. Adopting a shared decision-making approach to treatment may be useful particularly for long-term conditions; however, in some cases, this may be easier said than done due to both patients' and health professionals' sometimes discomfort with adopting such an approach. Training and support for both health professionals and patients may be helpful in facilitating a shared decision-making approach. PMID- 21982811 TI - A novel mutation in an atypical presentation of the rare infantile Farber disease. AB - BACKGROUND: Farber disease (MIM 228000) is a rare autosomal recessive condition caused by deficiency of lysosomal acid ceramidase (EC 3.5.1.23). The disease presents classically during the infantile period with a characteristic triad of clinical manifestations: (a) painful joints, (b) subcutaneous nodules, and (c) progressive hoarseness due to laryngeal involvement. All cases reported in the literature to date have presented with the above features, except for the neonatal-visceral subtype. METHODS: Here we describe a 2-year-old female, a product of a non-consanguineous Emirati union, who was quite well until 8 months of age when presented with failure to thrive, developmental delay with relative sparing of cognitive function, cherry-red spot, painful joint, progressive limitation of joint movement, and hoarseness of voice. The sibling of patient died with similar presentation and the nerve biopsy of deceased sibling showed features consistent with Farber disease. RESULTS: Gene sequencing of the ASAHI gene confirmed the diagnosis of Farber disease. Our patient has two heterozygous novel mutations, one in exon 8 (c.533 T>C) and the other in exon 13 (c.1144 A>C). The carrier status of the parents was confirmed. CONCLUSIONS: Farber disease is well known for its striking unique triad of symptoms. This study demonstrates that not all the cases essentially present with subcutaneous nodules which is considered a hallmark of the disease. PMID- 21982812 TI - Atonic variant of benign childhood epilepsy with centrotemporal spikes (atonic BECTS): a distinct electro-clinical syndrome. AB - PURPOSE: To describe the clinical and electroencephalographic features, treatment strategies and outcome in a series of children with the atonic variant of benign childhood epilepsy with centrotemporal spikes (atonic-BECTS). MATERIAL AND METHODS: Out of the 148 patients with BECTS reviewed from January 2005 to June 2010 in our Institute, there were seven (5%) with atonic-BECTS. All underwent video EEG, high-resolution magnetic resonance imaging (MRI), neuropsychological evaluation and language assessment. Their progress was followed. In addition to sodium valproate, three were treated with steroids, followed by intravenous immunoglobulin (IVIG) when the seizures relapsed while tapering or after stopping the steroids. RESULTS: All of the children had earlier onset (mean=2.4 years), increased frequency and increased duration of focal seizures compared to typical BECTS. Head drop and truncal sway due to axial or axiorhizomelic atonia occurring several times per day or week was the key manifestation. The atonic seizures worsened with carbamazepine in three, clonazepam in two and clobazam in one. When the atypical seizures commenced, some children developed one or more of the following problems: hyperactivity, attention deficit, clumsy gait, and mild cognitive or language dysfunction. Three children became seizure free, one on steroids and the other two on IVIG. CONCLUSIONS: BECTS in children with an early age of onset and frequent and prolonged seizures is more likely to evolve into atonic-BECTS. Carbamazepine and some benzodiazepines may worsen these seizures. Three children became seizure free with immunomodulatory therapy, one on steroids and the other two on IVIG, and had complete resolution of the transient motor and cognitive impairment. Atonic-BECTS needs to be differentiated from Lennox-Gastaut syndrome since it is potentially treatable and children recover with no sequel. Although all the children in this series continued to be on treatment with sodium valproate it is currently undetermined whether they would have required to do so if followed up for an extended period of time. PMID- 21982814 TI - Clinical characteristics and antibiotic resistance of Shigella gastroenteritis in Ankara, Turkey between 2003 and 2009, and comparison with previous reports. AB - OBJECTIVES: The aim of this study was to define the epidemiological, clinical, and antibiotic susceptibility patterns of Shigella gastroenteritis cases occurring during the years 2003-2009 and to compare results with those of the years 1987-2002. METHODS: A hospital-based study was conducted over a 22-year period. All 238 Shigella strains isolated between 2003 and 2009 were compared to 618 isolates from the period 1987-1994 and 218 Shigella strains isolated during 1995-2002 with regard to antimicrobial resistance patterns and patient clinical characteristics. RESULTS: The predominant species during all periods was Shigella sonnei, with an increasing predominance across the periods (64.0%, 71.5%, and 87.8%, respectively; p<0.001). Neither the prevalence of bloody diarrhea nor other clinical characteristics changed across the study periods, except for the prevalence of dehydration, which increased (11.0%, 20.6%, and 28.6%, respectively; p<0.001). During the period 2003-2009, 69.9% of Shigella were resistant to trimethoprim/sulfamethoxazole, 35.8% to ampicillin, and 4.7% to nalidixic acid. No case resistant to ciprofloxacin was detected. Multidrug resistance was also found to be similar in the last two periods (24.0% vs. 28.1%, respectively). CONCLUSIONS: There was both a microbiological and a clinical change in childhood Shigella gastroenteritis cases over the 22 years. The antibiotic resistance pattern appears to have remained stable over the last two periods. There is a need to re-examine the criteria and clinical management guidelines for suspected shigellosis cases. PMID- 21982813 TI - Neuroglial alterations in rats submitted to the okadaic acid-induced model of dementia. AB - Several types of animal models have been developed to investigate Alzheimer's disease (AD). Okadaic acid (OA), a potent inhibitor of phosphatases 1 and 2A, induces characteristics that resemble AD-like pathology. Memory impairment induced by intra-hippocampal injection of OA has been reported, accompanied by remarkable neuropathological changes including hippocampal neurodegeneration, a paired helical filament-like phosphorylation of tau protein, and formation of beta-amyloid containing plaque-like structures. Rats were submitted to bilateral intrahippocampal okadaic acid-injection (100 ng) and, 12 days after the surgery, behavioral and biochemical tests were performed. Using this model, we evaluated spatial cognitive deficit and neuroglial alterations, particularly astroglial protein markers such as glial fibrillary acidic protein (GFAP) and S100B, metabolism of glutamate, oxidative parameters and alterations in MAPKs. Our results indicate significant hippocampal changes, including increased GFAP, protein oxidation, and phosphorylation of p38(MAPK); and decreases in glutathione content, transporter EAAT2/GLT-1, and glutamine synthetase activity as well as a decrease in cerebrospinal fluid S100B. No alterations were observed in glutamate uptake activity and S100B content. In conclusion, the OA-induced model of dementia caused spatial cognitive deficit and oxidative stress in this model and, for the first time to our knowledge, specific astroglial alterations. Findings contribute to understanding diseases accompanied by cognitive deficits and the neural damage induced by AO administration. PMID- 21982815 TI - Recent developments in the diagnosis of ectoparasite infections and disease through a better understanding of parasite biology and host responses. AB - Some conventional methods of diagnosis of ectoparasite infections can have low sensitivity and/or specificity. In addition, early infestations, sub-clinical and carrier hosts often go un-diagnosed, allowing infestations to spread. This review focuses on the important ectoparasites of human, livestock and companion animals for which improved diagnostic tools are either already in use, or in development. These advances in diagnostic technologies have resulted in improved treatment, control and preventative strategies for many ectoparasitic diseases. Immunodiagnostic methods have had a large impact, with the emergence of highly sensitive and specific enzyme-linked immunosorbent assays (ELISAs) for sarcoptic and psoroptic mange, with further improved tests in development. In the present review, the advantages and limitations of such tests are discussed and the potential for future development explored. The increasing use of molecular tools, for example, PCR and other molecular methods, has improved our understanding of the epidemiology of ectoparasitic diseases, with practical consequences for community-based control programmes. Recently, the identification of specific signalling pathways during the host response to ectoparasites has led to the identification of disease biomarkers which, along with new technologies, such as multiplexed assays and microfluidic platforms, could lead to more cost-effective, rapid and accurate diagnosis of infectious diseases. PMID- 21982816 TI - Contribution of VEGF polymorphisms to variation in VEGF serum levels in a healthy population. AB - OBJECTIVE: Vascular endothelial growth factor (VEGF) is a pro-angiogenic factor. Variability in VEGF expression, induced by specific VEGFA variants, are involved in angiogenesis-related disorders. This study examined the genotype distribution and functional role (VEGF expression) of rs699947, rs833061, rs1570360, rs2010963, rs833068, rs833070, rs3025020, and rs3025039 VEGFA variants and their haplotypes in 519 healthy Bahraini individuals of both genders. METHODS AND RESULTS: The distribution of the eight VEGFA polymorphisms screened was in Hardy Weinberg equilibrium. The minor allele frequencies of rs699947 (0.42), rs833061 (0.32), rs1570360 (0.31), rs2010963 (0.33), rs833068 (0.37), rs833070 (0.42), rs3025020 (0.33), and rs3025039 (0.13) were generally compared to those established for Caucasians. Of the variants tested, rs3025020 was associated with increased VEGF serum levels (p=0.019), while rs3025039 was associated with decreased levels (p=0.038). Linkage analysis identified two VEGFA blocks, the first, spanning 16 kb, was not associated with altered VEGF levels, while the second, spanning 3 kb containing rs3025020 and rs3025039, was linked with higher VEGF expression, of which the (-583)T/(+936)T haplotype (p=0.008) was linked with higher VEGF levels compared to the (-583)C/(+936)C (all wild-type) haplotype. CONCLUSION: These results support the association of rs30250202 and rs3025039, and specific VEGF haplotypes, with altered VEGF serum levels, although the exact functional mechanisms remain to be elucidated. PMID- 21982817 TI - Abnormal ventilatory control in Parkinson's disease--further evidence for non motor dysfunction. AB - There has been increasing recognition of pre-motor manifestations of Parkinson's disease (PD) resulting from early brainstem involvement. We sought to determine whether ventilatory control is abnormal. Patients with PD without respiratory disease were recruited. Spirometry, lung volumes, diffusing capacity and respiratory muscle strength were assessed. Occlusion pressure and ventilation were measured with increasing CO(2). Arterial blood gases were taken at rest and following 20 min exposure to 15% O(2). A linear correlation assessed associations between respiratory function and indices of PD severity. 19 subjects (17 males) with mild-moderate PD were studied (mean (SD) age 66 (8) years). Respiratory flows and volumes were normal in 16/19. Maximum inspiratory and expiratory pressures were below LLN in 13/19 and 15/19 respectively. 7/15 had a reduced ventilatory response to hypercapnia and 11/15 had an abnormal occlusion pressure. There was no correlation between impairment of ventilatory response and reduction in respiratory muscle strength. Response to mild hypoxia was normal and there were no associations between disease severity and respiratory function. Our findings suggest that patients with mild-moderate PD have abnormal ventilatory control despite normal lung volumes and flows. PMID- 21982818 TI - Diversity and phylogenetic relationships among the North American Tacaribe serocomplex viruses (family Arenaviridae). AB - The purpose of this study was to extend our knowledge of the genetic diversity and phylogenetic relationships among the North American Tacaribe serocomplex viruses. Analyses of glycoprotein precursor gene sequence data separated the North American arenaviruses into 7 major phylogenetic groups. The results of analyses of Z gene and nucleocapsid protein gene sequence data were not remarkably different from the glycoprotein precursor gene tree. In contrast, the tree generated from RNA-dependent RNA polymerase gene sequences differed from the glycoprotein precursor gene tree with regard to phylogenetic relationships among the viruses associated with woodrats captured in the western United States, Texas, or northern Mexico. Further analyses of the polymerase gene sequence data set suggested that the difference in topology was a consequence of incongruence among the gene tree data sets or chance rather than genetic reassortment or recombination between arenaviruses. PMID- 21982819 TI - AAA ATPase p529 of Acidianus two-tailed virus ATV and host receptor recognition. AB - The two structural domains of p529, a predicted AAA ATPase of Acidianus two tailed virus (ATV), were expressed and purified. The N-terminal domain was demonstrated by loss-of-function mutations to carry ATPase activity with a temperature optimum of 60 degrees C. This domain also showed DNA binding activity that was stronger for the whole protein and was weakened in the presence of ATP. The C-terminal domain exhibits Mg(2+)-dependent endonuclease activity that was eliminated by site-directed mutagenesis at a conserved catalytic PD...D/ExK motif. p529 pull-down experiments with cell extracts of Sulfolobus solfataricus demonstrated a specific interaction with Sso1273, corresponding to OppA(Ss), an N linked glycoprotein that specifically binds oligopeptides. The sso1273 gene lies in an operon encoding an oligopeptide/dipeptide ABC transporter system. It is proposed that p529 is involved in ATV-host cell receptor recognition and possibly the endonuclease activity is required for cleavage of the circular viral DNA prior to cell entry. PMID- 21982820 TI - Facile production of Aspergillus niger alpha-N-acetylgalactosaminidase in yeast. AB - alpha-N-Acetylgalactosaminidase (alpha-GalNAc-ase; EC.3.2.1.49) is an exoglycosidase specific for the hydrolysis of terminal alpha-linked N acetylgalactosamine in various sugar chains. The cDNA corresponding to the alpha GalNAc-ase gene was cloned from Aspergillus niger, sequenced, and expressed in the yeast Saccharomyces cerevisiae. The alpha-GalNAc-ase gene contains an open reading frame which encodes a protein of 487 amino acid residues. The molecular mass of the mature protein deduced from the amino acid sequence of this reading frame is 54 kDa. The recombinant protein was purified to apparent homogeneity and biochemically characterized (pI4.4, K(M) 0.56 mmol/l for 2-nitrophenyl 2 acetamido-2-deoxy-alpha-d-galactopyranoside, and optimum enzyme activity was achieved at pH2.0-2.4 and 50-55 degrees C). Its molecular weight was determined by analytical ultracentrifuge measurement and dynamic light scattering. Our experiments confirmed that the recombinant alpha-GalNAc-ase exists as two distinct species (70 and 130 kDa) compared to its native form, which is purely monomeric. N-Glycosylation was confirmed at six of the eight potential N glycosylation sites in both wild type and recombinant alpha-GalNAc-ase. PMID- 21982821 TI - Effect of several analogs of 2,4,6-triphenyldioxane-1,3 on CYP2B induction in mouse liver. AB - 2,4,6-Triphenyldioxane-1,3 (TPD) is a highly effective inducer of CYP2V in rats, but not in mice. Several analogs of TPD were synthesized. All substituents were entered into the same position of TPD (R=H, cisTPD and transTPD; R=N(CH(3))(2), transpDMA; R=NO(2), transpNO(2); R=F, transpF; R=OCH(3), transpMeO). The purpose of the present study was to investigate the effect of TPD analogs on CYP2B induction in mouse livers. Among the six test compounds, four (R=-N(CH(3))(2), NO(2), -F, -OCH(3)) demonstrated a dose-dependent induction of mouse CYP2B. To further characterize the compounds, we determined ED50s using sigmoidal dose response curves. The dose-response study has shown that all active compounds have similar potencies to induce CYP2B in mouse livers. Western-blot analysis and multiplex RT-PCR have shown that the increase of CYP2B activity in mouse liver is related to the high content of CYP2B proteins and paralleled the increase of cyp2b10 mRNA level. ChIP results have demonstrated that the transcriptional enhancement of cyp2b10 gene in response to compounds is accompanied by the increased recruitment of the constitutive androstane receptor (CAR) to its specific binding site (PBREM) on the target gene. Thus, minor structural changes in TPD cause dramatic changes in its ability to induce mouse CYP2B, and it is likely several TPD analogs act by activation of mouse CAR. PMID- 21982823 TI - Interprosthetic femoral fractures: analysis of 14 cases. Proposal for an additional grade in the Vancouver and SoFCOT classifications. AB - INTRODUCTION: Interprosthetic fracture is a rare but serious entity, impairing consolidation and stability due to adverse mechanical conditions related to bone fragility and implant volume. OBJECTIVE: The present study highlights the difficulties involved in managing such fractures, details treatment options and reports findings leading to a proposed additional grade in the comparable Vancouver (hip) and French Orthopedic and Traumatologic Surgery Society (Societe francaise de chirurgie orthopedique et traumatologique: SoFCOT) (knee) classification systems. PATIENTS AND METHODS: A multicenter retrospective series included 14 interprosthetic femoral fractures: eight type double C (typeC for both hip and knee), five type C for hip and B for knee, and one type double B (type B for both hip and knee) on the Vancouver and SoFCOT classifications. Fracture occurred on standard (n=15) or revision (n =13) implants. Six cases involved a femoral shaft encumbered by a total knee replacement (TKR) femoral extension stem and eight cases TKR without femoral long stem, assimilable to type C fracture. RESULTS: None of the six fractures proximal to a constrained TKR with stem-achieved union by primary intention, whereas seven of the eight type-C fractures did so. Finally, 12 cases showed favorable evolution, with three secondary total femur replacements (TFR) and one death at 6 months without bony union or revision and one patient waiting for TFR. DISCUSSION: To describe the status of the intermediate femur and its medullary canal encumbrance, we propose adding a category D to the SoFCOT and Vancouver classifications, corresponding to interprosthetic fracture on TKR with diaphyseal extension stem. Interprosthetic fracture internal fixation should begin with long devices bridging the two prostheses. When the implant is loose, it may be replaced; in case of diaphyseal extension, however, the residual femur between the two extensions should be protected against peak stress by a plate extending upward and downward. In case of limited bone stock, due to osteolysis or initial femoral medullary canal compromise, especially if one or both implants are loose, TFR may be indicated as consolidation, is jeopardized by the uncertain mechanical situation. PMID- 21982822 TI - Interactions of cations with the cytoplasmic pores of inward rectifier K(+) channels in the closed state. AB - Ion channels gate at membrane-embedded domains by changing their conformation along the ion conduction pathway. Inward rectifier K(+) (Kir) channels possess a unique extramembrane cytoplasmic domain that extends this pathway. However, the relevance and contribution of this domain to ion permeation remain unclear. By qualitative x-ray crystallographic analysis, we found that the pore in the cytoplasmic domain of Kir3.2 binds cations in a valency-dependent manner and does not allow the displacement of Mg(2+) by monovalent cations or spermine. Electrophysiological analyses revealed that the cytoplasmic pore of Kir3.2 selectively binds positively charged molecules and has a higher affinity for Mg(2+) when it has a low probability of being open. The selective blocking of chemical modification of the side chain of pore-facing residues by Mg(2+) indicates that the mode of binding of Mg(2+) is likely to be similar to that observed in the crystal structure. These results indicate that the Kir3.2 crystal structure has a closed conformation with a negative electrostatic field potential at the cytoplasmic pore, the potential of which may be controlled by conformational changes in the cytoplasmic domain to regulate ion diffusion along the pore. PMID- 21982824 TI - Evidence of Methylobacterium spp. and Hyphomicrobium sp. in azaspiracid toxin contaminated mussel tissues and assessment of the effect of azaspiracid on their growth. AB - A flagellar protein belonging to the genus Methylobacterium or Agrobacterium was previously observed by proteomics in azaspiracids (AZA) toxic mussels. Here, we report the isolation of two different Methylobacterium spp. (NTx1 and Tx1) from non-toxic and AZA toxic mussels, respectively, which when co-cultured with AZA exhibited significantly different growth responses - isolate Tx1 growth rate was enhanced, whereas growth of isolate NTx1 was adversely affected, compared to non AZA supplemented control cultures. A Hyphomicrobium sp. (Tx2) also isolated from the toxic mussels achieved greater cell density in AZAs supplemented cultures. PMID- 21982825 TI - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a specific substrate of yeast metacaspase. AB - Yeast metacaspase (Yca1p) is required for the execution of apoptosis upon a wide range of stimuli. However, the specific degradome of this yeast protease has not been unraveled so far. By combining different methodologies described as requisites for a protein to be considered a protease substrate, such as digestome analysis, cleavage of recombinant GAPDH by metacaspase and evaluation of protein levels in vivo, we show that upon H(2)O(2)-induced apoptosis, the metabolic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a specific target of metacaspase. Nitric oxide (NO) signaling, which mediates H(2)O(2)-induced apoptosis, is required for metacaspase specific GAPDH cleavage. In conclusion, in this work we identified GAPDH as the first direct yeast metacaspase substrate described so far. Although mammalian caspases and yeast metacaspase apparently have distinct target cleavage sites, GAPDH arises as a common substrate for these proteases. PMID- 21982826 TI - The role of melatonin in parasite biology. AB - Regarded as the circadian hormone in mammals, melatonin is a highly conserved molecule, present in nearly all species. In this review, we discuss the role of this indolamine and its precursors in the cell biology of parasites and the role of the molecule in the physiology of the host. In Plasmodium, melatonin can modulate intracellular concentrations of calcium and cAMP, which in turn can regulate kinase activity and cell cycle. In Trypanosoma infections, modulation of the immune system by melatonin is extremely important in controlling the parasite population. Melatonin also contributes to the inflammatory response to Toxoplasma gondii infection. Thus, there are a number of unique adaptations involving intricate connections between melatonin and the biology of the parasite-host relationship. PMID- 21982827 TI - Differential antennal proteome comparison of adult honeybee drone, worker and queen (Apis mellifera L.). AB - To understand the olfactory mechanism of honeybee antennae in detecting specific volatile compounds in the atmosphere, antennal proteome differences of drone, worker and queen were compared using 2-DE, mass spectrometry and bioinformatics. Therefore, 107 proteins were altered their expressions in the antennae of drone, worker and queen bees. There were 54, 21 and 32 up-regulated proteins in the antennae of drone, worker and queen, respectively. Proteins upregulated in the drone antennae were involved in fatty acid metabolism, antioxidation, carbohydrate metabolism and energy production, protein folding and cytoskeleton. Proteins upregulated in the antennae of worker and queen bees were related to carbohydrate metabolism and energy production while molecular transporters were upregulated in the queen antennae. Our results explain the role played by the antennae of drone is to aid in perceiving the queen sexual pheromones, in the worker antennae to assist for food search and social communication and in the queen antennae to help pheromone communication with the worker and the drone during the mating flight. This first proteomic study significantly extends our understanding of honeybee olfactory activities and the possible mechanisms played by the antennae in response to various environmental, social, biological and biochemical signals. PMID- 21982829 TI - "Cheek-to-cheek" urinary proteome profiling via combinatorial peptide ligand libraries: A novel, unexpected elution system. AB - A new method is here reported for facile elution of the human urinary proteome after being captured with combinatorial peptide ligand libraries (CPLL, ProteoMiner). It consists in challenging the beads with 100mM Tris, pH 7.4, or with 100mM Lys, pH 7.4 or even better with a mixture of Lys, Arg, Asp and Glu (150mM final concentration). These elutions permit recovery of species in a native form, for monitoring any biological activity of the eluted species, while avoiding the noxious presence of sodium dodecyl sulphate (SDS), reported as the best eluant so far from CPLL beads. SDS, albeit permitting quantitative recovery from the beads, has to be removed from the sample prior to mass spectrometry analysis. This unorthodox elution, which most likely will work only for urine samples, seems to be due to the fact that bile salts and urinary pigments are massively adsorbed by the beads, thus masking the hydrophobic binding sites of aromatic and non-aromatic amino acids. The binding thus occurs mostly via ionic and hydrogen bond interactions via the "Grand Catchers" Arg, Lys, His, which can then be easily challenged by positively charged species, such a Tris, free Lys and free Arg in the eluant as well as by negatively charged compounds, such as Glu and Asp. When eluting with the four-amino acid mix, at least 3300 spots can be visualized in a 2D map. PMID- 21982828 TI - A differential proteomic approach identifies structural and functional components that contribute to the differentiation of brain capillary endothelial cells. AB - When in the vicinity of astrocytes, brain capillary endothelial cells (BCECs) develop the characteristic structural and functional features of the blood-brain barrier (BBB). The latter has low cellular permeability and restricts various compounds from entering the brain. We recently reported that the cytoskeleton related proteins actin, gelsolin and filamin-A undergo the largest quantitative changes in bovine BCECs after re-induction of BBB functions by co-culture with glial cells. In the present study, we used an in-depth, proteomic approach to quantitatively compare differences in Triton-X-100-solubilized proteins from bovine BCECs with limited or re-induced BBB functions (i.e. cultured in the absence or presence of glial cells, respectively). The 81 protein spots of differing abundance were linked to 55 distinct genes. According to the Protein ANalysis THrough Evolutionary Relationships classification system and an Ingenuity Pathway Analysis, these quantitative changes mainly affected proteins involved in (i) cell structure and motility and (ii) protein metabolism and modification. The fold-changes affecting HSPB1, moesin and ANXA5 protein levels were confirmed by western blot analysis but were not accompanied by changes in the corresponding mRNA expression levels. Our results reveal that the bovine BCECs' phenotype adaptation to variations in their environment involves the reorganization of the actin cytoskeleton. PMID- 21982830 TI - Global identification of transfer RNAs by liquid chromatography-mass spectrometry (LC-MS). AB - Transfer ribonucleic acid (tRNA) is the non-coding RNA that links the processes of gene transcription with protein translation. While tRNAs have, individually, been studied for many years, few approaches exist for the global identification of tRNAs at the RNA and posttranscriptional RNA levels. Previously our lab introduced the concept of signature enzymatic digestion products (SDPs) for tRNA identification using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). SDPs enable the direct determination of tRNA identity based on mass spectrometry detection of unique m/z values from enzymatic digestion products. Here we have examined the applicability of liquid chromatography-mass spectrometry (LC-MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS) for global identification of bacterial tRNAs via their SDPs using Escherichia coli as the model system. Optimal ultra high performance and high performance liquid chromatography (UPLC vs. HPLC) conditions were identified to address the hundreds of enzymatic digestion products present in the sample. The use of LC-MS/MS improves the accuracy of SDP assignments through confirming sequence information. The combination of mass unique SDP detection along with MS/MS sequencing yielded the identification of all tRNA families from E. coli and nearly doubles the number of specific SDPs detected over that previously obtained using MALDI-MS. This article is part of a Special Section entitled: Understanding genome regulation and genetic diversity by mass spectrometry. PMID- 21982831 TI - Focal adhesion kinase signaling mediates acute renal injury induced by ischemia/reperfusion. AB - Renal ischemia/reperfusion (I/R) injury is associated with cell matrix and focal adhesion remodeling. Focal adhesion kinase (FAK) is a nonreceptor protein tyrosine kinase that localizes at focal adhesions and regulates their turnover. Here, we investigated the role of FAK in renal I/R injury, using a novel conditional proximal tubule-specific fak-deletion mouse model. Tamoxifen treatment of FAK(loxP/loxP)//gammaGT-Cre-ER(T2) mice caused renal-specific fak recombination (FAK(DeltaloxP/DeltaloxP)) and reduction of FAK expression in proximal tubules. In FAK(DeltaloxP/DeltaloxP) mice compared with FAK(loxP/loxP) controls, unilateral renal ischemia followed by reperfusion resulted in less tubular damage with reduced tubular cell proliferation and lower expression of kidney injury molecule-1, which was independent from the postischemic inflammatory response. Oxidative stress is involved in the pathophysiology of I/R injury. Primary cultured mouse renal cells were used to study the role of FAK deficiency for oxidative stress in vitro. The conditional fak deletion did not affect cell survival after hydrogen peroxide-induced cellular stress, whereas it impaired the recovery of focal adhesions that were disrupted by hydrogen peroxide. This was associated with reduced c-Jun N-terminal kinase-dependent phosphorylation of paxillin at serine 178 in FAK-deficient cells, which is required for focal adhesion turnover. Our findings support a role for FAK as a novel factor in the initiation of c-Jun N-terminal kinase-mediated cellular stress response during renal I/R injury and suggest FAK as a target in renal injury protection. PMID- 21982833 TI - Antibiotic treatment duration for bloodstream infections in critically ill patients: a national survey of Canadian infectious diseases and critical care specialists. AB - An optimum duration of antibiotic therapy would eradicate infection whilst minimising adverse drug reactions, resistance and costs. However, there is a paucity of evidence guiding the duration of therapy for bloodstream infections. Canadian infectious diseases (ID) and critical care specialists were surveyed regarding their recommended antibiotic treatment durations for five common bacteraemic syndromes. A descriptive analysis was performed to assess: (i) practice heterogeneity; (ii) equipoise for a trial of shorter versus longer therapy; and (iii) the influence of pathogen and host characteristics on recommendations. In total, 172 clinicians responded to the survey (60% ID, 39% critical care and 1% combined specialists). For each syndrome, the most common recommendation was 14 days, yet the majority of respondents recommended durations of <= 10 days. Median durations were similar for each syndrome: central vascular catheter-related bloodstream infection, 10 +/- 3.6 days; bacteraemic pneumonia, 10 +/- 2.8 days; bacteraemic urinary tract infection, 10 +/- 3.8 days; bacteraemic intra-abdominal infection, 10 +/- 4.1 days; and bacteraemic skin and soft-tissue infection, 14 +/- 3.2 days. Respondents recommended the longest durations for Staphylococcus aureus and the shortest durations for coagulase negative staphylococci. Most respondents would not modify duration based on host characteristics or measures of clinical response. ID physicians recommended longer durations than critical care physicians for all five syndromes, but the majority of both specialist groups would enrol patients in a trial of shorter (7 day) versus longer (14 day) antibiotic therapy. In conclusion, significant practice variation exists amongst clinicians' recommended durations of antibiotic treatment for bacteraemia. There is equipoise for a randomised trial comparing shorter versus longer courses of antibiotics for most bacteraemic syndromes and pathogens. PMID- 21982832 TI - Stachybotrys chartarum-induced hypersensitivity pneumonitis is TLR9 dependent. AB - Hypersensitivity pneumonitis (HP), an inflammatory lung disease, develops after repeated exposure to inhaled particulate antigen and is characterized by a vigorous T helper type 1-mediated immune response, resulting in the release of IL 12 and interferon (IFN)-gamma. These T helper type 1 cytokines may participate in the pathogenesis of HP. Stachybotrys chartarum (SC) is a dimorphic fungus implicated in a number of respiratory illnesses, including HP. Here, we have developed a murine model of SC-induced HP that reproduces pathology observed in human HP and hypothesized that toll receptor-like 9 (TLR9)-mediated dendritic cell responses are required for the generation of granulomatous inflammation induced by inhaled SC. Mice sensitized and challenged with 10(6) SC spores develop granulomatous inflammation with multinucleate giant cells, accompanied by increased accumulation of neutrophils and CD4(+) and CD8(+) T cells. SC sensitization and challenge resulted in robust pulmonary expression of tumor necrosis factor-alpha, IL-12, and IFN-gamma. SC-mediated granulomatous inflammation required IFN-gamma and was TLR9 dependent, because TLR9(-/-) mice displayed reduced peribronchial inflammation, decreased accumulation and/or activation of polymorphonuclear (PMN) and CD4(+) and CD8(+) T cells, and reduced lung expression of type 1 cytokines and chemokines. T-cell production of IFN gamma was IL-12 dependent. Our studies suggest that TLR9 is critical for dendritic cell-mediated development of a type 1 granulomatous inflammation in the lung in response to SC. PMID- 21982834 TI - Comparison of microbiological and clinical characteristics based on SCCmec typing in patients with community-onset meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia. AB - Molecular identification methods based on the staphylococcal cassette chromosome mec (SCCmec) genotype are more reliable than clinical risk factors and demographic data for differentiating community-acquired and healthcare-associated (HCA) meticillin-resistant Staphylococcus aureus (MRSA). However, patients with community-onset (CO) MRSA infections, defined as a culture-positive sample obtained <48h after admission and from patients with HCA risk factors, have been infrequently studied. This study compared the clinical profiles of different SCCmec genotypes in this group of patients. From 2004 to 2008, the clinical profiles of 122 non-repetitive patients with CO-MRSA infections at a tertiary medical centre in Taiwan were retrospectively recorded and the molecular characteristics of the isolates were examined. The proportion of SCCmec IV/V genotypes increased from 9.5% to 35.3% from 2004 to 2008. There were no differences in demographic data, underlying diseases, invasive procedures or outcomes between the SCCmec II/III and IV/V groups, except that patients with SCCmec II/III genotypes tended to have more HCA risk factors (3.1 vs. 2.4; P=0.008). Multivariate logistic regression analysis revealed that having at least four HCA risk factors was independently associated with SCCmec II/III. The sensitivity of recovering SCCmec IV/V genotypes from patients with less than four HCA risk factors was 89.3%. This study revealed the emergence of SCCmec IV/V genotypes in CO-MRSA infections. Although the clinical characteristic boundaries between SCCmec II/III and IV/V diminished, having at least four HCA risk factors made the presence of SCCmec IV/V genotypes less likely in patients with CO-MRSA infections. PMID- 21982835 TI - Production of a plasmid-encoded OXA-72 beta-lactamase associated with resistance to carbapenems in a clinical isolate Acinetobacter junii. PMID- 21982836 TI - Residual dipolar coupling between quadrupolar nuclei under magic-angle spinning and double-rotation conditions. AB - Residual dipolar couplings between spin-1/2 and quadrupolar nuclei are often observed and exploited in the magic-angle spinning (MAS) NMR spectra of spin-1/2 nuclei. These orientation-dependent splittings contain information on the dipolar interaction, which can be translated into structural information. The same type of splittings may also be observed for pairs of quadrupolar nuclei, although information is often difficult to extract from the quadrupolar-broadened lineshapes. Here, the complete theory for describing the dipolar coupling between two quadrupolar nuclei in the frequency domain by Hamiltonian diagonalization is given. The theory is developed under MAS and double-rotation (DOR) conditions, and is valid for any spin quantum numbers, quadrupolar coupling constants, asymmetry parameters, and tensor orientations at both nuclei. All terms in the dipolar Hamiltonian become partially secular and contribute to the NMR spectrum. The theory is validated using experimental 11B and 35/37Cl NMR experiments carried out on powdered B-chlorocatecholborane, where both MAS and DOR are used to help separate effects of the quadrupolar interaction from those of the dipolar interaction. It is shown that the lineshapes are sensitive to the quadrupolar coupling constant of both nuclei and to the J coupling (including its sign). From these experiments, the dipolar coupling constant for a heteronuclear spin pair of quadrupolar nuclei may be obtained as well as the sign of the quadrupolar coupling constant of the perturbing nucleus; these are two parameters that are difficult to obtain experimentally otherwise. PMID- 21982837 TI - Simplified assessment of segmental gastrointestinal transit time with orally small amount of barium. AB - OBJECTIVE: To determine the effectiveness and advantage of small amount of barium in the measurement of gastrointestinal transmission function in comparison with radio-opaque pallets. METHODS: Protocal 1: 8 healthy volunteers (male 6, female 2) with average age 40+/-6.1 were subjected to the examination of radio-opaque pellets and small amount of barium with the interval of 1 week. Protocol 2: 30 healthy volunteers in group 1 (male 8, female 22) with average age 42.5+/-8.1 and 50 patients with chronic functional constipation in group 2 (male 11, female 39) with average age 45.7+/-7.8 were subjected to the small amount of barium examination. The small amount of barium was made by 30 g barium dissolved in 200 ml breakfast. After taking breakfast which contains barium, objectives were followed with abdominal X-ray at 4, 8, 12, 24, 48, 72, 96 h until the barium was evacuated totally. RESULTS: Small amount of barium presented actual chyme or stool transit. The transit time of radio-opaque pallets through the whole gastrointestinal tract was significantly shorter than that of barium (37+/-8 h vs. 47+/-10 h, P<0.05) in healthy people. The transit times of barium in constipation patients were markedly prolonged in colon (61.1+/-22 vs. 37.3+/-11, P<0.01) and rectum (10.8+/-3.7 vs. 2.3+/-0.8 h, P<0.01) compared with unconstipated volunteers. Transit times in individual gastrointestinal segments were also recorded by using small amount of barium, which allowed identifying the subtypes of constipation. CONCLUSION: The small amount barium examination is a convenient and low cost method to provide the most useful and reliable information on the transmission function of different gastrointestinal segments and able to classify the subtypes of slow transit constipation. PMID- 21982838 TI - Targeting the Wnt pathway in cancer: the emerging role of Dickkopf-3. AB - Aberrant activation of the Wnt signaling pathway is a major trait of many human cancers. Due to its vast implications in tumorigenesis and progression, the Wnt pathway has attracted considerable attention at several molecular levels, also with respect to developing novel cancer therapeutics. Indeed, research in Wnt biology has recently provided numerous clues, and evidence is accumulating that the secreted Wnt antagonist Dickkopf-related protein 3 (Dkk-3) and its regulators may constitute interesting therapeutic targets in the most important human cancers. Based on the currently available literature, we here review the knowledge on the biological role of Dkk-3 as an antagonist of the Wnt signaling pathway, the involvement of Dkk-3 in several stages of tumor development, the genetic and epigenetic mechanisms disrupting DKK3 gene function in cancerous cells, and the potential clinical value of Dkk-3 expression/DKK3 promoter methylation as a biomarker and molecular target in cancer diseases. In conclusion, Dkk-3 rapidly emerges as a key player in human cancer with auspicious tumor suppressive capacities, most of all affecting apoptosis and proliferation. Its gene expression is frequently downregulated by promoter methylation in almost any solid and hematological tumor entity. Clinically, evidence is accumulating of Dkk-3 being both a potential tumor biomarker and effective anti-cancer agent. Although further research is needed, re-establishing Dkk-3 expression in cancer cells holds promise as novel targeted molecular tumor therapy. PMID- 21982839 TI - Localisation of novel forms of glutamate transporters and the cystine-glutamate antiporter in the choroid plexus: Implications for CSF glutamate homeostasis. AB - The choroid plexus is a structure within each ventricle of the brain that is composed of fenestrated vessels surrounded by secretory epithelial cells. The epithelial cells are linked by tight junctions to create a permeability barrier. The epithelial cells are derived from neuroectoderm, and are thus defined by some authors as a subtype of macroglia. Glutamate is a tightly regulated substance in the CSF, as it is in the rest of the brain. In the brain macroglia express multiple sodium dependent and independent glutamate transporters and are the main regulators of extracellular glutamate. However, the identities of the transporters in the choroid plexus and their localisations have remained poorly defined. In this study we examined the expression and distribution of multiple splice variants of classical sodium-dependent glutamate transporters, as well as the cystine-glutamate antiporter, and the PDZ protein NHERF1, (which acts as a molecular anchor for proteins such as the glutamate transporter GLAST). We identified three forms of sodium-dependent transporters (GLAST1a, GLAST1c and GLT1b) that are expressed at the apical surface of the epithelial cells, a location that matches the distribution of NHERF1 and the cystine-glutamate antiporter. We propose that this coincident localisation of GLAST1a/GLAST1c/GLT1b and the cystine-glutamate antiporter would permit the cyclical trafficking of glutamate and thus optimise the accumulation of cystine for the formation of glutathione in the choroid plexus. PMID- 21982840 TI - Inactivation and injury assessment of Escherichia coli during solar and photocatalytic disinfection in LDPE bags. AB - Solar disinfection (SODIS) of Escherichia coli suspensions in low-density polyethylene bag reactors was investigated as a low-cost disinfection method suitable for application in developing countries. The efficiency of a range of SODIS reactor configurations was examined (single skin (SS), double skin, black backed single skin, silver-backed single skin (SBSS) and composite-backed single skin) using E. coli suspended in model and real surface water. Titanium dioxide was added to the reactors to improve the efficiency of the SODIS process. The effect of turbidity was also assessed. In addition to viable counts, E. coli injury was characterised through spread-plate analysis using selective and non selective media. The optimal reactor configuration was determined to be the SBSS bag (t(50)=9.0min) demonstrating the importance of UVA photons, as opposed to infrared in the SODIS disinfection mechanism. Complete inactivation (6.5-log) was achieved in the presence of turbidity (50NTU) using the SBSS bag within 180min simulated solar exposure. The addition of titanium dioxide (0.025gL(-1)) significantly enhanced E. coli inactivation in the SS reactor, with 6-log inactivation observed within 90min simulated solar exposure. During the early stages of both SODIS and photocatalytic disinfection, injured E. coli were detected; however, irreversible injury was caused and re-growth was not observed. Experiments under solar conditions were undertaken with total inactivation (6.5 log) observed in the SS reactor within 240min, incomplete inactivation (4-log) was observed in SODIS bottles exposed to the same solar conditions. PMID- 21982841 TI - Multiple skin lesions caused by Mycobacterium scrofulaceum infection. PMID- 21982842 TI - Mineral bridges in nacre. AB - We confirm with high-resolution techniques the existence of mineral bridges between superposed nacre tablets. In the towered nacre of both gastropods and the cephalopod Nautilus there are large bridges aligned along the tower axes, corresponding to gaps (150-200nm) in the interlamellar membranes. Gaps are produced by the interaction of the nascent tablets with a surface membrane that covers the nacre compartment. In the terraced nacre of bivalves bridges associated with elongated gaps in the interlamellar membrane (>100nm) have mainly been found at or close to the edges of superposed parental tablets. To explain this placement, we hypothesize that the interlamellar membrane breaks due to differences in osmotic pressure across it when the interlamellar space below becomes reduced at an advanced stage of calcification. In no cases are the minor connections between superimposed tablets (<60nm), earlier reported to be mineral bridges, found to be such. PMID- 21982843 TI - Plumbagin and juglone induce caspase-3-dependent apoptosis involving the mitochondria through ROS generation in human peripheral blood lymphocytes. AB - The phytochemicals plumbagin and juglone have recently been gaining importance because of their various pharmacological activities. In this study, these compounds are shown to induce concentration- and time-dependent toxicity in human peripheral blood lymphocytes via the apoptotic pathway. Flow cytometry data revealed the occurrence of about 28% early apoptotic cells after 6h exposure to 10MUM plumbagin and 35% late apoptotic cells and about 43% sub-G1 population after 24h. The cytotoxic effect of plumbagin was at least twofold higher than that of juglone as evidenced by the IC(50) value for cytotoxicity. Characteristic apoptotic features such as chromatin condensation and apoptotic body formation were observed through TEM, and membrane blebbing and cell surface smoothening were seen in SEM studies. Generation of ROS was evidenced through the HPLC analysis of superoxide-specific 2-OH-E+ formation. In addition, a decrease in GSH levels parallel to ROS production was observed. Reversal of apoptosis in both NAC and Tempol-pretreated cells indicates the involvement of both ROS generation and GSH depletion in plumbagin- and juglone-induced apoptosis. The mechanistic pathway involves a decrease in MMP; alterations in the levels of Bcl-2, Bax, and cytosolic cytochrome c; and PARP-1 cleavage subsequent to caspase-3 activation. PMID- 21982845 TI - A rhythmic change of vesicular glutamate transporter (VGLUT) 2 expression in the rat pineal gland. AB - The pineal gland secretes melatonin under circadian control via nocturnal noradrenergic stimulation, and expresses vesicular glutamate transporter (VGLUT) 1, VGLUT2 and a VGLUT1 splice variant (VGLUT1v). Although we previously reported that VGLUT2 mRNA level of rat pineal gland at postnatal day 21 is higher in the nighttime than in daytime, questions remained as to the time of postnatal onset of this phenomenon and a 24-h change in the mRNA or protein level at postnatal days. The day-night difference in VGLUT2 mRNA level was evident 14 days after birth. In the adult, VGLUT2 mRNA and protein levels increased in the dark phase, with the protein level showing a 6-h delay. The nocturnal elevation in VGLUT2 mRNA level diminished under the constant light condition but persisted under the constant dark condition. The present data suggest that VGLUT2 in the rat pineal gland is involved in some nocturnal glutamatergic function. PMID- 21982844 TI - Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease. AB - There is increasing evidence that the consumption of flavonoid-rich foods can beneficially influence normal cognitive function. In addition, a growing number of flavonoids have been shown to inhibit the development of Alzheimer disease (AD)-like pathology and to reverse deficits in cognition in rodent models, suggestive of potential therapeutic utility in dementia. The actions of flavonoid rich foods (e.g., green tea, blueberry, and cocoa) seem to be mediated by the direct interactions of absorbed flavonoids and their metabolites with a number of cellular and molecular targets. For example, their specific interactions within the ERK and PI3-kinase/Akt signaling pathways, at the level of receptors or kinases, have been shown to increase the expression of neuroprotective and neuromodulatory proteins and increase the number of, and strength of, connections between neurons. Concurrently, their effects on the vascular system may also lead to enhancements in cognitive performance through increased brain blood flow and an ability to initiate neurogenesis in the hippocampus. Additional mechanisms have been suggested for the ability of flavonoids to delay the initiation of and/or slow the progression of AD-like pathology and related neurodegenerative disorders, including a potential to inhibit neuronal apoptosis triggered by neurotoxic species (e.g., oxidative stress and neuroinflammation) or disrupt amyloid beta aggregation and effects on amyloid precursor protein processing through the inhibition of beta-secretase (BACE-1) and/or activation of alpha secretase (ADAM10). Together, these processes act to maintain the number and quality of synaptic connections in key brain regions and thus flavonoids have the potential to prevent the progression of neurodegenerative pathologies and to promote cognitive performance. PMID- 21982846 TI - Intestinal patches with an immobilized solid-in-oil formulation for oral protein delivery. AB - Oral administration of biomolecular drugs such as peptides, proteins, and DNA is an attractive delivery method because of the safety and convenience of delivery in contrast to injection administration. However, oral delivery of biomolecules has several potential barriers such as enzymatic degradation in the gastrointestinal tract and low permeability across an intestinal membrane. In this study, we proposed an intestinal patch system that included surfactant coated insulin for oral delivery. The intestinal patches, which have mucoadhesive and drug-impermeable layers, induced sustained unidirectional insulin release toward intestinal mucosa and inhibition of insulin leakage from the patches. Moreover, the surfactant-coated insulin, which has high compatibility with cell membranes, enhanced insulin transport across the intestinal membrane. This study demonstrates that the intestinal patches might improve protein permeability in the intestinal mucosa, thereby offering an innovative therapeutic strategy. PMID- 21982847 TI - A porous Cu/LDPE composite for copper-containing intrauterine contraceptive devices. AB - To improve the rates of both cupric ion release and the utilization of copper in non-porous copper/low-density polyethylene (Cu/LDPE) composite, a porous Cu/LDPE composite is proposed and developed in the present work. Here 2,5-di-tert butylhydroquinone was chosen as the porogen, ethyl acetate was chosen as the solvent for extraction, and the porous Cu/LDPE composite was obtained by using injection molding and the particulate leaching method. After any residual ethyl acetate remaining inside the porous Cu/LDPE composite had been removed by vacuum drying, the composite was characterized by X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, gas chromatography-mass spectrometry and absorption measurement. For comparison, a non-porous Cu/LDPE composite was also characterized in the same way. The results show that the porous structure was successfully introduced into the polymeric base of the non porous Cu/LDPE composite, and the porous Cu/LDPE composite is a simple hybrid of copper particles and porous LDPE. The results also show that the introduction of a porous structure can improve the cupric ion release rate of the non-porous Cu/LDPE composite with a certain content of copper particles, indicating that the utilization rate of copper can be improved either the introduction of a porous structure, and that the porous Cu/LDPE composite is another promising material for copper-containing intrauterine devices. PMID- 21982848 TI - A new tool for the transfection of corneal endothelial cells: calcium phosphate nanoparticles. AB - Calcium phosphate nanoparticles (CaP-NP) are ideal tools for transfection due to their high biocompatibility and easy biodegradability. After transfection these particles dissociate into calcium and phosphate ions, i.e. physiological components found in every cell, and it has been shown that the small increase in intracellular calcium level does not affect cell viability. CaP-NP functionalized with pcDNA3-EGFP (CaP/DNA/CaP/DNA) and stabilized using different amounts of poly(ethylenimine) (PEI) were prepared. Polyfect(r)-pcDNA3-EGFP polyplexes served as a positive control. The transfection of human and murine corneal endothelial cells (suspensions and donor tissue) was optimized by varying the concentration of CaP-NP and the duration of transfection. The transfection efficiency was determined as EGFP expression detected by flow cytometry and fluorescence microscopy. To evaluate the toxicity of the system the cell viability was detected by TUNEL staining. Coating with PEI significantly increased the transfection efficiency of CaP-NP but decreased cell viability, due to the cytotoxic nature of PEI. The aim of this study was to develop CaP-NP with the highest possible transfection efficiency accompanied by the least apoptosis in corneal endothelial cells. EGFP expression in the tissues remained stable as corneal endothelial cells exhibit minimal proliferative capacity and very low apoptosis after transfection with CaP-NP. In summary, CaP-NP are suitable tools for the transfection of corneal endothelial cells. As CaP-NP induce little apoptosis these nanoparticles offer a safe alternative to viral transfection agents. PMID- 21982849 TI - Time-resolved MR angiography of the calf arteries using a phased array cardiac coil: comparison of visibility with standard three-step bolus chase MR angiography. AB - BACKGROUND: Standard bolus chase MR angiography (MRA) is increasingly replacing digital subtraction angiography (DSA) in the diagnostic evaluation of peripheral vascular disease. However, a major limitation of bolus chase MRA is the relatively poor visibility of the calf arteries. PURPOSE: To evaluate the feasibility of visualizing the calf arteries and the visibility quality of an 8 channel cardiac phased array coil using time-resolved imaging of contrast kinetics (TRICKS) MRA compared with standard bolus chase MRA on a 1.5 Tesla MRI scanner. MATERIAL AND METHODS: MRA findings of 59 sequential patients (mean age 57.8 years, range 14-83 years; 41 men) were retrospectively evaluated. All examinations included preliminary TRICKS for the lower leg using a surface 8 channel cardiac coil, followed by a 3-step MRA of the abdominal aorta, thigh, and lower leg using a body coil. Images yielded by both methods were separately evaluated by consensus of two radiologists unaware of the patients' clinical data. Visibility of the calf arteries (popliteal, tibialis anterior, tibialis posterior, tibioperoneal trunk, and peroneal) for both sides was subjectively classified as 'diagnostic' or 'non-diagnostic'. Descriptive statistics for image diagnostic quality were assessed. RESULTS: A total of 575 calf arterial segments were evaluated. Visibility of all calf arteries was significantly better with TRICKS than with the standard bolus chase MRA (P < 0.001). The improvement of calf artery visibility with TRICKS was more pronounced in patients with peripheral vascular disease compared to those with arteritis, vascular malformation and popliteal entrapment syndrome. CONCLUSION: Using a cardiac coil for MRA of the lower extremities resulted in visibility comparable to that of a dedicated leg coil, with diagnostic superiority for the TRICKS method compared to the standard bolus chase method. PMID- 21982850 TI - Post-licensure evaluation of vaccine safety: current status and future directions. Symposium organised by the International Alliance for Biological Standardization (IABS) in Barcelona, Spain, 27-28 April 2011. AB - Adverse events following immunization, while rare, unfortunately do occur. And when they do, the public's faith in vaccines waves. It's a known fact, for example, that vaccine safety concerns are among the most important factors contributing to parents refusing vaccination for their children. How best, then, to tackle these concerns and increase public confidence in the vaccine safety system? In an effort to contribute to identifying the right mechanisms, the International Alliance for Biological Standardization organized an international symposium on "Post-Licensure Evaluation of Vaccine Safety" in Barcelona in early Spring. Delegates from 24 countries took a close look at the current status of this challenging problem and identified several practical measures which could help address the situation. They suggested an integrated vaccine safety program to be in place in all countries and standardized so that information and data can be exchanged on a routine basis. Another proposal was to put in place simple measures such as the use of bar codes on vaccine vials. PMID- 21982851 TI - Validation of model virus removal and inactivation capacity of an erythropoietin purification process. AB - Human erythropoietin (hEpo) production requires mammalian cells able to make complex post-translational modifications to guaranty its biological activity. As mammalian cell can be reservoir of pathogenic viruses and several animal origin components are usually used in the cultivation of mammalian cells, hEpo contamination with viruses is something of great concern. As consequence, this study investigated the viral removal and inactivation capacity of a recombinant hEpo (rec-hEpo) purification process. Canine parvovirus, Human poliovirus type-2, Bovine viral diarrhea virus and Human immunodeficiency virus type-1 were used for measuring process viral removal and inactivation capacities. In conclusion, this study corroborated that the assessed rec-hEpo purification process has enough capacity (5.0-19.4 Logs) for removing and inactivating these model viruses and sodium hydroxide demonstrated to be a robust sanitization solution for chromatography columns (5.0 (PV-2)-6.7 (CPV) Logs). PMID- 21982852 TI - Vaccination of sex reversed hybrid tilapia (Oreochromis niloticus * O. aureus) with an inactivated Vibrio vulnificus vaccine. AB - Vibrio vulnificus causes disease in economically important aquaculture raised fish and is an opportunistic human pathogen. This study reports on the isolation of V. vulnificus from diseased hybrid tilapia (Oreochromis niloticus * O. aureus) cultured in a North American water reuse facility. Our objectives were to characterize the isolate using biochemical and molecular methods, develop a disease challenge model, and determine the ability of a formalin inactivated whole-cell vaccine to protect against V. vulnificus. The V. vulnificus isolate recovered was biotype 1, 16S rRNA type B, vcg type C, and vvhA type 2 and caused disease in tilapia held in static salt water (1.5 g/l sea salt). Fish vaccinated with the formalin inactivated whole-cell vaccine responded to vaccination with titers from vaccinated fish ranging from 32 to 64 and titers from non-vaccinated fish ranging from 4 to 8. In two trials, vaccinated tilapia exhibited relative percent survival (RPS) of 73 and 60% following homologous isolate challenge. In two additional trials, vaccinated tilapia exhibited RPS values of up to 88% following challenge with a heterologous isolate; the use of a mineral oil adjuvant enhanced protection. This vaccine may provide an effective means of preventing infections caused by biochemically and genetically diverse V. vulnificus. PMID- 21982853 TI - Non-tubal ectopic pregnancy. PMID- 21982854 TI - Using a GIS to model interventions to strengthen the emergency referral system for maternal and newborn health in Ethiopia. AB - OBJECTIVES: To show how GIS can be used by health planners to make informed decisions about interventions to increase access to emergency services. METHODS: A combination of data sources, including the 2008 national Ethiopian baseline assessment for emergency obstetric and newborn care that covered 797 geo-coded health facilities, LandScan population data, and road network data, were used to model referral networks and catchment areas across 2 regions of Ethiopia. STATA and ArcGIS software extensions were used to model different scenarios for strengthening the referral system, defined by the structural inputs of transportation and communication, and upgrading facilities, to compare the increase in access to referral facilities. RESULTS: Approximately 70% of the population of Tigray and Amhara regions is served by facilities that are within a 2-hour transfer time to a hospital with obstetric surgery. By adding vehicles and communication capability, this percentage increased to 83%. In a second scenario, upgrading 7 strategically located facilities changed the configuration of the referral networks, and the percentage increased to 80%. By combining the 2 strategies, 90% of the population would be served by midlevel facilities within 2 hours of obstetric surgery. The mean travel time from midlevel facilities to surgical facilities would be reduced from 121 to 64 minutes in the scenario combining the 2 interventions. CONCLUSIONS: GIS mapping and modeling enable spatial and temporal analyses critical to understanding the population's access to health services and the emergency referral system. The provision of vehicles and communication and the upgrading of health centers to first level referral hospitals are short- and medium-term strategies that can rapidly increase access to lifesaving services. PMID- 21982855 TI - User fees and maternity services in Ethiopia. AB - OBJECTIVES: To examine user fees for maternity services and how they relate to provision, quality, and use of maternity services in Ethiopia. METHODS: The national assessment of emergency obstetric and newborn care (EmONC) examined user fees for maternity services in 751 health facilities that provided childbirth services in 2008. RESULTS: Overall, only about 6.6% of women gave birth in health facilities. Among facilities that provided delivery care, 68% charged a fee in cash or kind for normal delivery. Health centers should be providing maternity services free of charge (the healthcare financing proclamation), yet 65% still charge for some aspect of care, including drugs and supplies. The average cost for normal and cesarean delivery was US $7.70 and US $51.80, respectively. Nineteen percent of these facilities required payment in advance for treatment of an obstetric emergency. The health facilities that charged user fees had, on average, more delivery beds, deliveries (normal and cesarean), direct obstetric complications treated, and a higher ratio of skilled birth attendants per 1000 deliveries than those that did not charge. The case fatality rate was 3.8% and 7.1% in hospitals that did and did not charge user fees, respectively. CONCLUSION: Utilization of maternal health services is extremely low in Ethiopia and, although there is a government decree against charging for maternity service, 65% of health centers do charge for some aspects of maternal care. As health facilities are not reimbursed by the government for the costs of maternity services, this loss of revenue may account for the more and better services offered in facilities that continue to charge user fees. User fees are not the only factor that determines utilization in settings where the coverage of maternity services is extremely low. Additional factors include other out-of pocket payments such as cost of transport and food and lodging for accompanying relatives. It is important to keep quality of care in mind when user fees are under discussion. PMID- 21982856 TI - Education and capacity building are the future. PMID- 21982857 TI - Editor's final comment. PMID- 21982858 TI - Attitudes of Ghanaian women toward genetic testing for sickle cell trait. AB - OBJECTIVE: To explore the attitudes of Ghanaian women toward genetic testing for the sickle cell trait and to investigate key factors that promote or impede the decision to pursue knowledge of the carrier status. METHODS: A survey, administered in person to Ghanaian women, collected demographic information and information on the participants' knowledge about their carrier status, their attitudes toward genetic testing, and their perceptions of the implications of being a carrier. The results for women who had previously undergone testing and those who had not were compared. RESULTS: Of 124 participants, 75 had been tested for the sickle cell trait and 49 had not. Some 53% of the women who had been tested did not know their carrier status. Most women agreed that getting a prenatal genetic test was important. However, nontested women were more likely to lack the financial resources to undergo testing, to think that testing is futile because sickle cell disease is not curable, and to believe that the outcome of their child's health is determined by God. CONCLUSION: The women tended to have favorable attitudes toward genetic testing, but numerous barriers remained that precluded knowledge of their carrier status or the pursuit of this knowledge. PMID- 21982860 TI - A secreted protein microarray platform for extracellular protein interaction discovery. AB - Characterization of the extracellular protein interactome has lagged far behind that of intracellular proteins, where mass spectrometry and yeast two-hybrid technologies have excelled. Improved methods for identifying receptor-ligand and extracellular matrix protein interactions will greatly accelerate biological discovery in cell signaling and cellular communication. These technologies must be able to identify low-affinity binding events that are often observed between membrane-bound coreceptor molecules during cell-cell or cell-extracellular matrix contact. Here we demonstrate that functional protein microarrays are particularly well-suited for high-throughput screening of extracellular protein interactions. To evaluate the performance of the platform, we screened a set of 89 immunoglobulin (Ig)-type receptors against a highly diverse extracellular protein microarray with 686 genes represented. To enhance detection of low-affinity interactions, we developed a rapid method to assemble bait Fc fusion proteins into multivalent complexes using protein A microbeads. Based on these screens, we developed a statistical methodology for hit calling and identification of nonspecific interactions on protein microarrays. We found that the Ig receptor interactions identified using our methodology are highly specific and display minimal off-target binding, resulting in a 70% true-positive to false-positive hit ratio. We anticipate that these methods will be useful for a wide variety of functional protein microarray users. PMID- 21982859 TI - Introduction of misoprostol for prevention of postpartum hemorrhage at the community level in Senegal. AB - OBJECTIVE: To demonstrate that training ensures correct administration of oral misoprostol by auxiliary midwives for prevention of postpartum hemorrhage (PPH) among women giving birth at the community level in Senegal. METHODS: A 6-day training program for auxiliary midwives and supervisors, including 1 day of PPH prevention training and a practicum of 10 deliveries at health centers and 3 deliveries at maternity huts, was conducted in 2 Senegalese districts in June July 2009. Data were collected between July and December 2009 on the administration of oral misoprostol by trained auxiliary midwives among 245 women giving birth at health centers, health posts, and maternity huts. RESULTS: All participating women received the correct administration of oral misoprostol; however, few women delivering in the community-based maternity huts received the supervision that is locally required to administer misoprostol. Women were willing to pay for some or all of the costs of misoprostol for PPH prevention. CONCLUSION: Timely management of PPH is essential to reduce maternal mortality. With limited training, auxiliary midwives achieved the correct administration of oral misoprostol that can attain this goal. Community delivery supervised by a skilled attendant limits access to, and need not be a requirement for, PPH prevention. PMID- 21982861 TI - Measurement of marine osmolytes in mammalian serum by liquid chromatography tandem mass spectrometry. AB - Osmolytes are accumulated intracellularly to offset the effects of osmotic stress and protect cellular proteins against denaturation. Because different taxa accumulate different osmolytes, they can also be used as "dietary biomarkers" to study foraging. Potential osmolyte biomarkers include glycine betaine, trimethylamine N-oxide (TMAO), homarine, dimethylsulfoniopropionate (DMSP), and the osmolyte analog arsenobetaine (AsB). We present a liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for the simultaneous measurement of these osmolytes in serum or plasma. Varying concentrations of osmolytes were added to serum and samples and extracted in 90% acetonitrile and 10% methanol containing 10 MUM deuterated internal standards (D(9)-glycine betaine, D(9) trimethylamine-N-oxide, (13)C(2)-arsenobetaine, D(6)-DMSP, and D(4)-homarine). Analytes were separated on a normal-phase modified silica column and detected using isotope dilution tandem mass spectrometry in multiple reaction monitoring (MRM) mode. The assay was linear for all six compounds (r(2) values=0.983-0.996). Recoveries were greater than 85%, and precision for within-batch coefficients of variation (CVs) were less than 8.2% and between-batch CVs were less than 6.1%. Limits of detection ranged from 0.02 to 0.12 MUmol/L. LC-MS/MS is a simple method with high throughput for measuring low levels of osmolytes that are often present in biological samples. PMID- 21982862 TI - Chip-based cartilage oligomeric matrix protein detection in serum and synovial fluid for osteoarthritis diagnosis. AB - We have developed a method to detect cartilage oligomeric matrix protein (COMP) as a specific biomarker of osteoarthritis (OA). In pathological conditions of the cartilage, COMP is released first into the synovial fluid (SF) and from there into the blood. Thus, measurement of COMP in the blood and SF facilitates OA diagnosis. To determine COMP, we developed a fluoro-microbead guiding chip (FMGC) based immunoassay. The FMGC has four immunoreactive regions, each with five patterns, to allow multiple assays. A COMP-specific capture antibody was immobilized to the FMGC surface to create a self-assembled interfacial layer. SF or serum samples from patients with OA possessing the target COMP were applied to the COMP-sensing monolayer. To generate binding signal, COMP detection antibody conjugated fluoro-microbeads were applied and the numbers of fluoro-microbeads bound specifically were counted to determine COMP concentrations. This FMGC-based immunoassay clearly distinguished immunospecific from nonspecific binding by comparing optical signals from inside and outside of the patterns. The optical signals showed linear correlations with serum and SF COMP concentrations. Optical detection and quantification of COMP using fluorescence microscopy correlated well with results from commercial enzyme-linked immunosorbent assay (ELISA). This FMGC-based immunoassay offers a new approach for detecting a clinically relevant biomarker for OA in human blood and SF. PMID- 21982863 TI - In situ characterization of antibody grafting on porous monolithic supports. AB - The efficient immobilization of antibodies on monolithic support is one of the most critical steps when preparing immunoaffinity supports. In this work, the ADECA (amino density estimation by colorimetric assay) method was adapted to tridimensional supports (in a dynamic mode) and proved to be efficient to characterize the antibodies grafting efficiency on 15.3+/-0.9mg porous glycidyl methacrylate (GMA)-co-ethylene dimethacrylate (EDMA) monolithic columns. The amount of grafted antibodies measured in situ on the monolith by ADECA (8.2+/ 0.2MUg of antibodies per milligram of monolith) was consistent with values obtained by bicinchoninic acid assay (BCA) after crushing the monolith. ADECA was shown to be less time-consuming and more versatile than BCA. The ADECA method was further implemented to thoroughly study and optimize the antibody grafting conditions (influence of pH and kinetics of the grafting step) on GMA-based monoliths and to check the covalent nature of the antibody/surface linking and its stability. Using the total amount of grafted antibodies and the amount of recognized antigen, we found that 65+/-6% of antibodies were able to capture their antigen. Finally, the grafting of Fab and F(ab')(2) fragments demonstrated that no significant improvement of the global binding capacity of the monolith was obtained. PMID- 21982864 TI - Secreted heat shock protein-90 (Hsp90) in wound healing and cancer. AB - Extracellular Hsp90 proteins, including "membrane-bound", "released" and "secreted", were first reported more than two decades ago. Only studies of the past 7years have begun to reveal a picture for when, how and why Hsp90 gets exported by both normal and tumor cells. Normal cells secrete Hsp90 in response to tissue injury. Tumor cells have managed to constitutively secrete Hsp90 for tissue invasion. In either case, sufficient supply of the extracellular Hsp90 can be guaranteed by its unusually abundant storage inside the cells. A well characterized function of secreted Hsp90alpha is to promote cell motility, a crucial event for both wound healing and cancer. The reported targets for extracellular Hsp90alpha include MMP2, LRP-1, tyrosine kinase receptors and possibly more. The pro-motility activity of secreted Hsp90alpha resides within a fragment, called 'F-5', at the boundary between linker region and middle domain. Inhibition of its secretion, neutralization of its extracellular action or interruption of its signaling through LRP-1 block wound healing and tumor invasion in vitro and in vivo. In normal tissue, topical application of F-5 promotes acute and diabetic wound healing far more effectively than US FDA approved conventional growth factor therapy in mice. In cancer, drugs that selectively target the F-5 region of secreted Hsp90 by cancer cells may be more effective and less toxic than those that target the ATPase of the intracellular Hsp90. This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90). PMID- 21982865 TI - Linking impulsivity and inhibitory control using manual and oculomotor response inhibition tasks. AB - Separate cognitive processes govern the inhibitory control of manual and oculomotor movements. Despite this fundamental distinction, little is known about how these inhibitory control processes relate to more complex domains of behavioral functioning. This study sought to determine how these inhibitory control mechanisms relate to broadly defined domains of impulsive behavior. Thirty adults with attention-deficit/hyperactivity disorder (ADHD) and 28 comparison adults performed behavioral measures of inhibitory control and completed impulsivity inventories. Results suggest that oculomotor inhibitory control, but not manual inhibitory control, is related to specific domains of self-reported impulsivity. This finding was limited to the ADHD group; no significant relations between inhibitory control and impulsivity were found in comparison adults. These results highlight the heterogeneity of inhibitory control processes and their differential relations to different facets of impulsivity. PMID- 21982867 TI - Temperature effects on the magnetoplasmon spectrum of a weakly modulated graphene monolayer. AB - In this work, we determine the effects of temperature on the magnetoplasmon spectrum of an electrically modulated graphene monolayer as well as a two dimensional electron gas (2DEG). The intra-Landau band magnetoplasmon spectrum within the self-consistent field approach is investigated for both the aforementioned systems. Results obtained not only exhibit Shubnikov-de Haas (SdH) oscillations but also commensurability oscillations (Weiss oscillations). These oscillations are periodic as a function of inverse magnetic field. We find that both the magnetic oscillations, SdH and Weiss, have a greater amplitude and are more robust against temperature in graphene compared to a conventional 2DEG. Furthermore, there is a pi phase shift between the magnetoplasmon oscillations in the two systems which can be attributed to Dirac electrons in graphene acquiring a Berry's phase as they traverse a closed path in a magnetic field. PMID- 21982866 TI - Molecular dynamic simulation study of cholesterol and conjugated double bonds in lipid bilayers. AB - Conjugated linoleic acids (CLA) are found naturally in dairy products. Two isomers of CLA, that differ only in the location of cis and trans double bonds, are found to have distinct and different biological effects. The cis 9 trans 11 (C9T11) isomer is believed to have anti-carcinogenic effects, while the trans 10 cis 12 (T10C12) isomer is believed to be associated with anti-obesity effects. In this paper we extend earlier molecular dynamics (MD) simulations of pure CLA phosphatidylcholine bilayers to investigate the comparative effects of cholesterol on bilayers composed of the two respective isomers. Simulations of phosphatidylcholine lipid bilayers in which the sn-2 chains contained one of the two isomers of CLA were performed in which, for each isomer, the simulated bilayers contained 10% and 30% cholesterol (Chol). From MD trajectories we calculate and compare structural properties of the bilayers, including areas per molecule, thickness of bilayers, tilt angle of cholesterols, order parameter profiles, and one and two-dimensional radial distribution function (RDF), as functions of Chol concentration. While the structural effect of cholesterol is approximately the same for both isomers, we find differences at an atomistic level in order parameter profiles and in two-dimensional radial distribution functions. PMID- 21982868 TI - Dual targeted delivery of doxorubicin to cancer cells using folate-conjugated magnetic multi-walled carbon nanotubes. AB - By combining the advantage of multi-walled carbon nanotubes (MWCNTs) and iron oxide magnetic nanoparticles (MNs), we develop a magnetic dual-targeted nanocarrier for drug delivery. MWCNTs were functionalized with poly(acrylic acid) through free radical polymerization, decorated with MNs, conjugated with a targeting ligand folic acid (FA), for loading of an anti-cancer drug doxorubicin (DOX). The proposed methodology provides dual targeted delivery of the anti cancer drug to cancer cells under the guidance of a magnetic field and through ligand-receptor interactions. The chemico-physical properties of the nanocarrier were characterized, in addition to its drug loading efficiency and drug releasing characteristics. Doxorubicin could be loaded to MWCNTs with high efficiency via pi-pi stacking and hydrogen bonding and showed enhanced cytotoxicity toward U87 human glioblastoma cells compared with free DOX. From transmission electron microscopy and confocal laser scanning microscopy, we confirmed that DOX-FA-MN MWCNT could be efficiently taken up by U87 cells with subsequent intracellular release of DOX, followed by transport of DOX into the nucleus with the nanocarrier left in the cytoplasm. These properties make the magnetic nanocarrier a potential candidate for targeted delivery of DOX for cancer treatment. PMID- 21982869 TI - Effects of ONO-5334, a novel orally-active inhibitor of cathepsin K, on bone metabolism. AB - In the present study, we examined the in vitro and in vivo pharmacological effects of ONO-5334, a novel inhibitor of cathepsin K, on bone metabolism. In vitro experiments indicated that ONO-5334 is a potent inhibitor of cathepsin K with Ki value of 0.1 nM. Although this compound inhibited other cysteine proteases, such as cathepsin S, L and B, its inhibitory activity for these enzymes was 8 to 320 fold lower than that for cathepsin K. ONO-5334 also inhibited human osteoclasts bone resorption in vitro at a concentration more than 100 fold lower than that of alendronate, a bisphosphonate. While alendronate disrupted actin ring and induced pyknotic nuclei in osteoclasts, ONO-5334 did not have such effects, suggesting that this compound does not affect osteoclasts viability. In in vivo experiments, oral administration of ONO-5334 dose dependently reduced plasma calcium level increased by parathyroid hormone related peptide in thyroparathyroidectomized rats. Furthermore, in vivo experiment using normal monkeys demonstrated that ONO-5334 decreases serum and urine C-telopeptide of type I collagen level, a bone resorption marker, soon after oral dosing. These levels were consistently decreased below pre-dose levels by repeated oral dosing with ONO-5334 for 7 days. ONO-5334 on the other hand did not affect bone formation markers, serum osteocalcin and bone specific alkaline phosphatase. These findings indicate that ONO-5334 is a specific inhibitor for cathepsin K and thus may be a novel therapeutic agent for metabolic bone diseases. PMID- 21982870 TI - Binocular capture: the effects of spatial frequency and contrast polarity of the monocular target. AB - The influence of binocular disparate targets on the perceived visual direction of adjacent monocular targets has been termed "binocular capture". The magnitude of capture increases significantly with increasing vertical separation between monocular targets. This study sets out to elucidate the interaction between spatial frequency content, contrast polarity and vertical separation between monocular targets to establish the roles of the monocular target's positional uncertainty and the underlying position-encoding mechanism in the production of binocular capture. Relative alignment thresholds and bias were measured separately for a pair of vertically separated monocular Vernier spatial frequency ribbons and a pair of monocular Gaussian bars presented across a random dot stereogram. Ribbon pairs comprised carrier frequencies that were either matched (8 cpd or 1 cpd) or mismatched (top ribbon 1 cpd, bottom ribbon 8 cpd, and vice versa). The Gaussian bars were presented with either matched contrast (bright/bright) or opposite polarity (bright/dark) contrast. Capture magnitudes increased significantly with vertical separation for all ribbon conditions and for both contrast polarity conditions. In these conditions, capture magnitude co varied with relative alignment threshold. The matched 1 cpd ribbons showed a significant effect of separation and relative alignment threshold on capture magnitude for low contrast stimuli but not for high contrast stimuli. The results are consistent with the hypothesis that perceived visual direction of a monocular target becomes increasingly dependent on the surround visual direction when its relative position signals are poor. Furthermore, its vulnerability to capture by the surround visual direction seems to be dependent on the underlying position encoding mechanism employed to compute relative position information of the monocular target. PMID- 21982871 TI - The relationship between walking, manual dexterity, cognition and activity/participation in persons with multiple sclerosis. AB - BACKGROUND: Multiple sclerosis has a vast impact on health, but the relationship between walking, manual dexterity, cognition and activity/participation is unclear. OBJECTIVE: The specific aims were to explore the discriminative ability of measures of walking, manual dexterity and cognition, and to identify cut-off values in these measures, for prediction of independence in personal and instrumental activities of daily living (ADL) and activity/participation in social and lifestyle activities. METHODS: Data from 164 persons with multiple sclerosis were collected during home visits with the following measures: the 2 * 5 m walk test, the Nine-hole Peg Test, the Symbol Digit Modalities Test, the Katz Personal and Instrumental ADL Indexes, and the Frenchay Activities Index (measuring frequency in social and lifestyle activities). RESULTS: The 2 * 5 m walk test and the Nine-hole Peg Test had high and better discriminative and predictive ability than the Symbol Digit Modalities Test. Cut-off values were identified. The accuracy of predictions was increased above all by combining the 2 * 5 m walk test and the Nine-hole Peg Test. CONCLUSION: The proposed cut-off values in the 2 * 5 m walk test and the Nine-hole Peg Test may be used as indicators of functioning and to identify persons risking activity limitations and participation restrictions. However, further studies are needed to confirm the usefulness in clinical practice. PMID- 21982872 TI - Cesarean delivery may increase the risk of multiple sclerosis. AB - BACKGROUND: Prenatal and perinatal factors are believed to contribute to the risk of developing multiple sclerosis (MS). OBJECTIVE: This study was designed to evaluate whether mode of delivery (vaginal versus cesarean section), as a perinatal factor, affects susceptibility to MS. METHODS: MS patients were recruited from the MS registry of Isfahan Multiple Sclerosis Society (IMSS) and were compared with their healthy siblings. Data regarding mode of delivery, birth order, and gestation week of birth were obtained through a specially designed questionnaire. Preterm or post term deliveries were excluded. We used conditional logistic regression statistics and adjusted for gender and birth order. RESULTS: This study included 1349 participants (449 MS patients and 900 controls). Subjects who were born by cesarean section had significant risk of MS (odds ratio, OR = 2.51; 95% confidence interval, CI: 1.43-4.41; p = 0.001). There was significant MS risk for females who were born by cesarean section (OR = 2.69, 95% CI: 1.30-5.58; p = 0.008), but not for males (OR = 2.25, 95% CI: 0.90-5.63; p = 0.082). The mean age at onset was lower in MS patients born by cesarean section (24.58 +/- 6.33) compared with that of patients born by vaginal delivery (27.59 +/- 7.97; p = 0.041). There was no significant difference between the two groups for birth order (p = 0.417). CONCLUSION: Our results suggest that those born by vaginal delivery are at a lower risk of subsequent MS. These preliminary findings will need to be addressed in a much larger and preferably prospective study. PMID- 21982873 TI - Weight cycling and cancer: weighing the evidence of intermittent caloric restriction and cancer risk. AB - Overweight and obese individuals frequently restrict caloric intake to lose weight. The resultant weight loss, however, typically is followed by an equal or greater weight gain, a phenomenon called weight cycling. Most attention to weight cycling has focused on identifying its detrimental effects, but preclinical experiments indicating that intermittent caloric restriction or fasting can reduce cancer risk have raised interest in potential benefits of weight cycling. Although hypothesized adverse effects of weight cycling on energy metabolism remain largely unsubstantiated, there is also a lack of epidemiologic evidence that intentional weight loss followed by regain of weight affects chronic-disease risk. In the limited studies of weight cycling and cancer, no independent effect on postmenopausal breast cancer but a modest enhancement of risk for renal cell carcinoma, endometrial cancer, and non-Hodgkin's lymphoma have been reported. An effect of either intermittent caloric restriction or fasting in protecting against cancer is not supported by the majority of rodent carcinogenesis experiments. Collectively, the data argue against weight cycling and indicate that the objective of energy balance-based approaches to reduce cancer risk should be to strive to prevent adult weight gain and maintain body weight within the normal range defined by body mass index. PMID- 21982874 TI - Modulation of gene expression and cell-cycle signaling pathways by the EGFR inhibitor gefitinib (Iressa) in rat urinary bladder cancer. AB - The epidermal growth factor receptor inhibitor Iressa has shown strong preventive efficacy in the N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN) model of bladder cancer in the rat. To explore its antitumor mechanism, we implemented a systems biology approach to characterize gene expression and signaling pathways in rat urinary bladder cancers treated with Iressa. Eleven bladder tumors from control rats, seven tumors from rats treated with Iressa, and seven normal bladder epithelia were profiled by the Affymetrix Rat Exon 1.0 ST Arrays. We identified 713 downregulated and 641 upregulated genes in comparing bladder tumors versus normal bladder epithelia. In addition, 178 genes were downregulated and 96 genes were upregulated when comparing control tumors versus Iressa-treated tumors. Two coexpression modules that were significantly correlated with tumor status and treatment status were identified [r = 0.70, P = 2.80 * 10(-15) (bladder tumor vs. normal bladder epithelium) and r = 0.63, P = 2.00 * 10(-42) (Iressa-treated tumor vs. control tumor), respectively]. Both tumor module and treatment module were enriched for genes involved in cell-cycle processes. Twenty-four and twenty-one highly connected hub genes likely to be key drivers in cell cycle were identified in the tumor module and treatment module, respectively. Analysis of microRNA genes on the array chips showed that tumor module and treatment module were significantly associated with expression levels of let-7c (r = 0.54, P = 3.70 * 10(-8) and r = 0.73, P = 1.50 * 10(-65), respectively). These results suggest that let-7c downregulation and its regulated cell-cycle pathway may play an integral role in governing bladder tumor suppression or collaborative oncogenesis and that Iressa exhibits its preventive efficacy on bladder tumorigenesis by upregulating let-7 and inhibiting the cell cycle. Cell culture study confirmed that the increased expression of let-7c decreases Iressa-treated bladder tumor cell growth. The identified hub genes may also serve as pharmacodynamic or efficacy biomarkers in clinical trials of chemoprevention in human bladder cancer. PMID- 21982875 TI - Inflammatory marker changes in a yearlong randomized exercise intervention trial among postmenopausal women. AB - Chronic low-grade inflammation is a possible risk factor for cancer that may be modifiable with long-term exercise. Very few randomized controlled trials (RCT) have studied the isolated effects of exercise on low-grade inflammation exclusively in postmenopausal women. The Alberta Physical Activity and Breast Cancer Prevention Trial, a 2-armed RCT in healthy postmenopausal women, examined how 1 year of moderate to vigorous aerobic exercise, compared with usual inactivity, influenced circulating inflammatory markers. Baseline, 6-month, and 12-month serum was analyzed by direct chemiluminescent immunoassays to measure high sensitivity C-reactive protein (CRP) and ELISAs to measure interleukin 6 (IL 6) and TNF-alpha. Intention to treat analyses were conducted with linear mixed models. Statistically significant differences in CRP were observed over 12 months for exercisers versus controls (treatment effect ratio = 0.87, 95% CI = 0.79 0.96, P = 0.005), but not in IL-6 or TNF-alpha. A statistically significant trend (P(trend) = 0.021) of decreasing CRP with increasing exercise adherence and stronger intervention effects on CRP in women with higher baseline physical fitness (P(heterogeneity) = 0.040) was found. The intervention effect on CRP became statistically nonsignificant with adjustment for dietary fiber intake change and seemed to be mediated by fat loss. Low-grade inflammation may be lowered with exercise, but confounding by dietary intake occurred and should be considered in future studies. Further trials are needed to corroborate our findings about the optimal dose of exercise required to lower CRP levels and effect modification of CRP changes by levels of body fatness and fitness. PMID- 21982876 TI - Characterization of subpopulations and immune-related parameters of hemocytes in the green-lipped mussel Perna viridis. AB - The green-lipped mussel Perna viridis is distributed widely in the estuarine and coastal areas of the Indo-Pacific region and extensively cultured as an inexpensive protein source. Morphology and immunological activities of hemocytes of P. viridis were investigated using flow cytometry and light and electron microscopy. Three major types of hemocytes were identified in the hemolymph, including dense-granulocyte, semi-granulocyte (small and large size) and hyalinocyte. Other hemocytes, which occurred in low numbers, included granulocytes with different electron-dense/lucent granules and hemoblast-like cells. Based on flow cytometry, two subpopulations were identified. Granulocytes were larger cells, and the more abundant, containing numerous granules in the cytoplasm, and hyalinocytes were the smaller and less abundant with the fewest granules. Flow cytometry revealed that the granulocytes were more active in cell phagocytosis, contained the higher lysosomal content, and showed higher esterase activity and reactive oxygen species (ROS) generation compared with hyalinocytes. Immune functions assessed by the flow cytometry indicated that the granulocytes were the main hemocytes involved in the cellular defence in P. viridis. PMID- 21982877 TI - South American camelid illegal traffic detection by means of molecular markers. AB - South American camelids comprise the wild species guanaco and vicuna and their respective domestic relatives llama and alpaca. The aim of the present study was to determine by DNA analysis to which of these species belong a herd of camelids confiscated from a llama breeder but alleged to be alpacas by the prosecution, and to evaluate the usefulness of mitochondrial and autosomal DNA markers to solve judicial cases involving camelid taxa. Cytochrome b and cytochrome oxidase I mitochondrial genes and 7 STR were analyzed in 25 confiscated samples. Mitochondrial results were inconclusive because 18 of the sequestered samples presented haplotypes that corresponded to the guanaco haplogroup and the remaining seven belonged to a vicuna linage. Microsatellite data of casework samples and llama reference samples revealed different genetic profiles by the presence of private alleles at two microsatellites suggesting that the confiscated animals could be alpaca, or at least alpaca hybrids instead of pure llama. PMID- 21982878 TI - Use of postmortem computed tomography to reveal an intraoral gunshot injuries in a charred body. AB - A 53-year-old man was found dead after a fire at his residence had been extinguished. Although a pistol was recovered beside the body, external examination was unable to indicate any gunshot wound because of severe charring of the body. Postmortem computed tomography (CT) scan performed prior to autopsy suggested an entrance gunshot wound in the posterior pharynx with loss of soft tissue and an internal bullet path through the right anterior and posterior parts of the occipital bone. Autopsy revealed an entrance gunshot wound with hemorrhage in the soft tissue of the posterior pharynx, massive contusion of the right occipital lobe, and subarachnoid hemorrhage in the right temporal lobe, both occipital lobes and the superior surface of the left cerebellar hemisphere, thus being consistent with the findings of postmortem CT. A carboxyhemoglobin concentration of 5% in blood from the cadaver was consistent with the lack of soot deposition from the larynx to the bronchus. These observations confirmed that death had been caused by an intraoral gunshot resulting in severe brain damage, before the body had been burned. PMID- 21982881 TI - Characterization of BARD1 targeting and dynamics at the centrosome: the role of CRM1, BRCA1 and the Q564H mutation. AB - BARD1 heterodimerizes with BRCA1, forming an E3 ubiquitin ligase that functions at nuclear foci to repair DNA damage and the centrosome to regulate mitosis. We compared BARD1 recruitment at these structures using fluorescence recovery after photobleaching assays to measure YFP-BARD1 dynamics in live cells. In nuclei at ionizing radiation-induced foci, 20% of the BARD1 pool was immobile and 80% of slow mobility exhibiting a recovery time >500 s. In contrast, at centrosomes 83% of BARD1 was rapidly mobile with extremely fast turnover (recovery time ~20s). The ~25-fold faster exchange of BARD1 at centrosomes correlated with BRCA1 independent recruitment. We mapped key targeting sequences to a combination of the N and C-termini, and showed that mutation of the nuclear export signal reduced centrosome localization by 50%, revealing a role for CRM1. Deletion of the sequence 128-550 increased BARD1 turnover at the centrosome, consistent with a role in transient associations. Conversely, the cancer mutation Q564H reduced turnover by 25%. BARD1 is one of the most highly mobile proteins yet detected at the centrosome, and in contrast to its localization at DNA repair foci, which requires dimerization with BRCA1, targeting of BARD1 to the centrosome occurs prior to heterodimerization and its rapid turnover may provide a mechanism to regulate dimer formation. PMID- 21982879 TI - Cellular signaling and biological functions of R-spondins. AB - R-spondins (RSPOs) are a family of cysteine-rich secreted proteins containing a single thrombospondin type I repeat (TSR) domain. A vast amount of information regarding cellular signaling and biological functions of RSPOs has emerged over the last several years, especially with respect to their roles in the activation of the WNT signaling pathway. The identification of several classes of RSPO receptors may indicate that this family of proteins can affect several signaling cascades. Herein, we summarize the current understanding of RSPO signaling and its biological functions, and discuss its potential therapeutic implications to human diseases. PMID- 21982880 TI - Angiotensin II induces nephrin dephosphorylation and podocyte injury: role of caveolin-1. AB - Nephrin, an important structural and signal molecule of podocyte slit-diaphragm (SD), has been suggested to contribute to the angiotensin II (Ang II)-induced podocyte injury. Caveolin-1 has been demonstrated to play a crucial role in signaling transduction. In the present study, we evaluated the role of caveolin-1 in Ang II-induced nephrin phosphorylation in podocytes. Wistar rats-receiving either Ang II (400 ng/kg/min) or normal saline (via subcutaneous osmotic mini pumps, control) were administered either vehicle or telmisartan (3 mg/kg/min) for 14 or 28 days. Blood pressure, 24-hour urinary albumin and serum biochemical profile were measured at the end of the experimental period. Renal histomorphology was evaluated through light and electron microscopy. In vitro, cultured murine podocytes were exposed to Ang II (10(-6)M) pretreated with or without losartan (10(-5) M) for variable time periods. Nephrin and caveolin-1 expression and their phosphorylation were analyzed by Western-blotting and immunofluorescence. Caveolar membrane fractions were isolated by sucrose density gradient centrifugation, and then the distribution and interactions between Ang II type 1 receptor (AT1), nephrin, C-terminal Src kinase (Csk) and caveolin-1 were evaluated using Western-blotting and co-immunoprecipitation. Podocyte apoptosis was evaluated by cell nucleus staining with Hoechst-33342. Ang II receiving rats displayed diminished phosphorylation of nephrin but enhanced glomerular/podocyte injury and proteinuria when compared to control rats. Under control conditions, podocyte displayed expression of caveolin-1 in abundance but only a low level of phospho moiety. Nonetheless, Ang II stimulated caveolin-1 phosphorylation without any change in total protein expression. Nephrin and caveolin-1 were co-localized in caveolae fractions. AT1 receptors and Csk were moved to caveolae fractions and had an interaction with caveolin-1 after the stimulation with Ang II. Transfection of caveolin-1 plasmid (pEGFPC3-cav-1) significantly increased Ang II-induced nephrin dephosphorylation and podocyte apoptosis. Furthermore, knockdown of caveolin-1 expression (using siRNA) inhibited nephrin dephosphorylation and prevented Ang II-induced podocyte apoptosis. These findings indicate that Ang II induces nephrin dephosphorylation and podocyte injury through a caveolin-1-dependent mechanism. PMID- 21982883 TI - Long-term results of non-fludarabine versus fludarabine-based stem cell transplantation without total body irradiation in Fanconi anemia patients. AB - BACKGROUND AND OBJECTIVE: Hematopoietic cell transplantation (HCT) is the only therapeutic modality capable of correcting the hematologic manifestations of Fanconi anemia (FA). The development of well-tolerated immunosuppressive conditioning regimens for FA patients undergoing HCT has proven to be a challenging task for hematologists. DESIGN AND SETTINGS: Retrospective, patients referred to the hematology, oncology and stem cell transplantation research center. PATIENTS AND METHODS: We analyzed the outcome of 53 FA patients who had undergone HCT between 1992 and 2010. The median age at transplantation was 9 years. Patients received transplants from an HLA-identical sibling (n=39) or matched relative (n=9) and one-antigen locus mismatched other relative/sibling (n=5). All of the patients underwent transplantation with fludarabine and non fludarabine-based conditioning regimens. No radiation therapy was given. RESULTS: The median follow-up period for survivors was 13.5 months (range, 3 months-13.5 years). The 3-year overall survival (OS) was 60.6%. The 3-year OS for patients who did or did not receive fludarabine-based preparative regimens for the allograft was 36.4%, and 70%, respectively. However, there were no statistically significant differences in OS rates between these two groups (P=.112). Graft failure occurred in 4 patients (7.5%). All of these 4 patients had received fludarabine-based conditioning regimens. The incidence of acute GVHD after fludarabine-based regimens was 45% versus 79% in non-fludarabine-based regimens (P=.03). CONCLUSION: Despite the high incidence of acute GVHD (78.6%) in the non fludarabine group, which resulted in the death of some patients, the OS rate was significantly better than in fludarabine recipients. Therefore, in spite of the fact that recent studies advocate the fludarabine-based conditioning regimens, we propose to conduct a multicenter, prospective study to evaluate the outcomes of regimens employed in FA patients. PMID- 21982884 TI - The challenges of managing glioblastoma multiforme in developing countries: a trade-off between cost and quality of care. AB - BACKGROUND AND OBJECTIVES: The management of glioblastoma multiforme (GBM) in developing countries is hindered by the paucity of clear protocols due in part to growing economic constraints and the lack of availability of expensive chemotherapeutic agents. We evaluated the deliverable treatment protocols and achievable outcomes for patients with GBM in a low-income country prior and subsequent to the worldwide adoption of temozolomide. DESIGN AND SETTING: Retrospective case series. PATIENTS AND METHODS: Charts of consecutive patients with a pathologic diagnosis of high-grade glioma diagnosed between January 2003 and December 2008 were retrospectively reviewed. RESULTS: We identified 146 adult patients, including 105 males and 41 females between 19 and 81 years of age (median age, 51 years), with histologically confirmed high-grade glioma. All patients underwent craniotomy. Eighty-two patients were treated with radiotherapy and temozolomide, of whom 42 patients received temozolomide concurrent with radiation followed by adjuvant temozolomide; 40 patients received irradiation followed sequentially by 6 cycles of temozolomide. In 40 patients irradiation was utilized as a single modality treatment adjuvant to surgery. The follow-up ranged from 1 to 56 months (median, 9.4 months). The median survival for the whole cohort was 10.2 months. The median survival for the radiotherapy-alone group was 5.3 months and for combined radiotherapy/temozolomide was 14.8 months. Survival was similar in both concurrent and sequential groups. Temozolomide conferred a statistically significant survival benefit of 9 months compared with standard therapeutic modalities. CONCLUSIONS: The results compare favorably to those reported in developed nations. Current management of GBM in developing countries should include maximal surgical resection followed by radiotherapy/temozolomide whenever medically and/or financially feasible. Outcomes comparable to those obtained within the context of randomized trials can be expected in low-income settings if healthcare delivery is carefully planned. Our results indicate that concurrent and sequential regimens are equally effective in these patients. PMID- 21982882 TI - The renaissance of Ca2+-binding proteins in the nervous system: secretagogin takes center stage. AB - Effective control of the Ca(2+) homeostasis in any living cell is paramount to coordinate some of the most essential physiological processes, including cell division, morphological differentiation, and intercellular communication. Therefore, effective homeostatic mechanisms have evolved to maintain the intracellular Ca(2+) concentration at physiologically adequate levels, as well as to regulate the spatial and temporal dynamics of Ca(2+)signaling at subcellular resolution. Members of the superfamily of EF-hand Ca(2+)-binding proteins are effective to either attenuate intracellular Ca(2+) transients as stochiometric buffers or function as Ca(2+) sensors whose conformational change upon Ca(2+) binding triggers protein-protein interactions, leading to cell state-specific intracellular signaling events. In the central nervous system, some EF-hand Ca(2+)-binding proteins are restricted to specific subtypes of neurons or glia, with their expression under developmental and/or metabolic control. Therefore, Ca(2+)-binding proteins are widely used as molecular markers of cell identity whilst also predicting excitability and neurotransmitter release profiles in response to electrical stimuli. Secretagogin is a novel member of the group of EF hand Ca(2+)-binding proteins whose expression precedes that of many other Ca(2+) binding proteins in postmitotic, migratory neurons in the embryonic nervous system. Secretagogin expression persists during neurogenesis in the adult brain, yet becomes confined to regionalized subsets of differentiated neurons in the adult central and peripheral nervous and neuroendocrine systems. Secretagogin may be implicated in the control of neuronal turnover and differentiation, particularly since it is re-expressed in neoplastic brain and endocrine tumors and modulates cell proliferation in vitro. Alternatively, and since secretagogin can bind to SNARE proteins, it might function as a Ca(2+) sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. Thus, secretagogin emerges as a functionally multifaceted Ca(2+) binding protein whose molecular characterization can unravel a new and fundamental dimension of Ca(2+)signaling under physiological and disease conditions in the nervous system and beyond. PMID- 21982885 TI - Outcome of allogeneic stem cell transplantation with a conditioning regimen of busulfan, cyclophosphamide and low-dose etoposide for children with myelodysplastic syndrome. AB - BACKGROUND AND OBJECTIVES: Allogeneic stem cell transplantation (SCT) offers the best chance of cure and long-term survival for children with myelodysplastic syndromes (MDS). DESIGN AND SETTING: Retrospective analysis of pediatric patients with primary MDS treated with allogeneic SCT at a single institution treated between January 1993 and December 2008. PATIENTS AND METHODS: Of 16 consecutive children who received allogeneic SCT for treatment of MDS in our center, 14 patients met the criteria of MDS according WHO I and II criteria. The median age was 4.8 years (range, 1-14 years) and 64% were male. The median time from diagnosis to transplant was 6 months. MDS stage was refractory cytopenia (RC) in 9, refractory anemia with excess blasts (RAEB) in 5. Monosomy 7 was present in 35% of the patients. The majority of patients (11/14) were conditioned with a busulfan-based myeloablative (MA) regimen with addition of low-dose of etoposide (30 mg/kg). All but one received a bone marrow graft. RESULTS: Nine patients achieved complete remission (CR), and seven remain alive. At a median follow-up of 3 years (range, 2-14 years) the OS and EFS was 57% (95%CI, 0.28-0.78). Cumulative EFS at 10 years was 43% (95% CI, 0.14-0.70). Relapse-related mortality was 21.4%; nonrelapse mortality (NRM) was 28.57%. All the survivors had etoposide in their conditioning regimen. Patients younger than 10 years had better survival (P=.001). CONCLUSION: Children with MDS achieve encouraging OS and EFS following allogeneic SCT. A busulfan-based regimen with a lower dose of etoposide is an effective and less toxic regimen. The outcomes are best in younger patients. PMID- 21982886 TI - Retinoblastoma in Jordan: an epidemiological study (2006-2010). AB - BACKGROUND AND OBJECTIVE: The epidemiological characteristics of retinoblastoma have been extensively studied in developed countries, however epidemiological data is scarce in the Middle East. We present a de- tailed epidemiological analysis of retinoblastoma in Jordan in an attempt to aid national and regional strategies for improved cancer surveillance and control. DESIGN AND SETTING: Retrospective review of retinoblastoma cases presenting to the sole and exclusive ocular oncology referral center in Jordan. PATIENTS AND METHODS: Forty children (59 eyes) presenting with clinically and/or histologically confirmed retinoblastomas were treated at King Hussein Cancer Center (Amman, Jordan) between January 2006 and December 2010. This case series included 28 boys and 12 girls. Data relating to age at diagnosis, laterality, gender, treatment modality and survival were recorded. RESULTS: The mean age-adjusted incidence of retinoblastoma in Jordan was 9.32 cases per million children per year for children aged 0-5 years. The male: female ratio was 2.3:1. Bilateral cases were encountered in 19 pa- tients (47.5%) while 21 patients (52.5%) harbored unilateral retinoblastoma. At the time of follow-up, 38 patients (95%) were alive. Overall, 40 eyes (67.8%) were successfully preserved without the need for enucleation. CONCLUSIONS: The national epidemiological data gathered in this study indicates that the incidence of retinoblastoma in Jordan is similar to that reported in various countries of the world. Jordanian boys, however, are at significantly higher risk for developing retinoblastoma than age-matched girls. Furthermore, Jordanian patients are more likely to harbor bilateral retinoblastoma. PMID- 21982887 TI - Small lymphocytic lymphoma in a patient with CREST syndrome. AB - We report a case of a 61-year-old man with a history of CREST syndrome (calcinosis cutis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) who presented for evaluation of thrombocytopenia. He had evident cervical adenopathy and lymph node biopsy showed small lymphocytic lymphoma (SLL) with evident systemic adenopathy and bone marrow involvement. The patient achieved a complete remission with FCR (fludarabine/cyclophosphamide/rituximab) chemotherapy. About 30 cases of lymphomas are reported in the literature in association with systemic sclerosis. To our knowledge, there are no reports of a small lymphocytic lymphoma (SLL) in association with limited cutaneous systemic sclerosis with classic features of the CREST syndrome. PMID- 21982888 TI - Association of hyperplastic polyposis syndrome, colorectal cancer and meningioma. AB - Recent research has provided compelling evidence that a subset of hyperplastic polyps may be associated with a risk of colorectal cancer. Colorectal cancer with extracolonic manifestation is usually seen in a hereditary syndrome setting, but some association with meningioma has been reported. The association of colorectal cancer with hyperplastic polyposis and meningioma is extremely rare. This report in a 57-year-old female with no family history of colon cancer or polyps, could be the first case of hyperplastic polyposis syndrome, colorectal cancer and meningioma. Hyperplastic polyposis syndrome was diagnosed as per WHO criteria at the time of colon cancer diagnosis. Within 4 months of colon cancer diagnosis she developed seizures. Imaging of the brain revealed meningioma of the left cerebellopontine angle. The patient underwent surgery followed by chemotherapy. PMID- 21982889 TI - Mediastinal endodermal sinus tumor associated with fatal hemophagocytic syndrome. AB - The association of endodermal sinus tumor, known also as yolk sac tumor, of the mediastinum with hemophagocytic syndrome is exceedingly rare with only a few cases on record. We report a 24-year-old male who had a large mediastinal germ cell tumor, proven to be an endodermal sinus tumor on biopsy. The patient developed pancytopenia and coagulopathy related to associated hemophagocytic syndrome, with a fatal outcome. A brief review of the relevant literature is presented as well. PMID- 21982890 TI - Acute massive splenic infarction with complete liquefaction of the spleen in sickle cell disease. PMID- 21982891 TI - Uterine sarcoma: a rare cause of uterine inversion. PMID- 21982892 TI - Lead intoxication mimicking a malignancy. PMID- 21982893 TI - Vascular-type Ehlers-Danlos syndrome presenting as recurrent compartment syndrome. PMID- 21982894 TI - Heme oxygenase 1 is induced by miR-155 via reduced BACH1 translation in endothelial cells. AB - Heme oxygenase 1 (HO-1) is a stress-inducible enzyme that degrades redox-active heme-producing biliverdin, carbon monoxide, and Fe(2+). It protects cells under various stress conditions and mediates anti-inflammatory and vasodilatory effects in the endothelium. The expression of HMOX1, the HO-1 gene, is highly inducible and its transcriptional regulation is complex. HMOX1 is induced by various proinflammatory stimuli via NF-kappaB in human endothelial cells, but functional NF-kappaB-binding elements have not been identified from the human gene. However, the regulation of HMOX1 by the antioxidant-response element is firmly established, with the transcription factor BACH1 serving as a repressor and Nrf2 as an enhancer. miR-155 is one of the TNFalpha-inducible endothelial microRNAs predicted to bind to the BACH1 mRNA. Oligonucleotides mimicking miR-155 efficiently inhibited BACH1 protein translation, resulting in a concentration dependent increase in HMOX1 mRNA and protein expression in human umbilical vein endothelial cells. Moreover, endogenous miR-155 was upregulated by TNFalpha via an NF-kappaB-dependent mechanism with a subsequent increase in HMOX1 expression. We propose that increased HMOX1 expression in endothelial cells by TNFalpha results from miR-155-induced repression of BACH1 rather than direct induction of HMOX1 via NF-kappaB, and that miR-155 is cytoprotective during inflammation by elevating HO-1 expression in endothelial cells. PMID- 21982895 TI - An essential difference in the reactivity of the glutathione adducts of the structurally closely related flavonoids monoHER and quercetin. AB - During the scavenging of free radicals flavonoids are oxidized to electrophilic quinones. Glutathione (GSH) can trap these quinones, thereby forming GSH flavonoid adducts. The aim of this study was to compare the stability of the GSH flavonoid adduct of 7-mono-O-(beta-hydroxyethyl)rutoside (monoHER) with that of quercetin. It was found that GSH-quercetin reacts with the thiol N-acetyl-L cysteine (NAC) to form NAC-quercetin, whereas GSH-monoHER does not react with NAC. In addition, the adduct of the monoHER quinone with the dithiol dithiothreitol (DTT) is relatively stable, whereas the DTT-quercetin adduct is readily converted into quercetin and DTT disulfide. These differences in reactivity of the thiol-flavonoid adducts demonstrate that GSH-monoHER is much more stable than GSH-quercetin. This difference in reactivity was corroborated by molecular quantum chemical calculations. Thus, although both flavonoid quinones are rapidly scavenged by GSH, the advantage of monoHER is that it forms a stable conjugate with GSH, thereby preventing a possible spread of toxicity. These findings demonstrate that even structurally comparable flavonoids behave differently, which will be reflected in the biological effects of these flavonoids. PMID- 21982896 TI - Pulmonary hypertension in the newborn GTP cyclohydrolase I-deficient mouse. AB - Tetrahydrobiopterin (BH4) is a regulator of endothelial nitric oxide synthase (eNOS) activity. Deficient levels result in eNOS uncoupling, with a shift from nitric oxide to superoxide generation. The hph-1 mutant mouse has deficient GTP cyclohydrolase I (GTPCH1) activity, resulting in low BH4 tissue content. The adult hph-1 mouse has pulmonary hypertension, but whether such condition is present from birth is not known. Thus, we evaluated newborn animals' pulmonary arterial medial thickness, biopterin content (BH4+BH2), H(2)O(2) and eNOS, right ventricle-to-left ventricle+septum (RV/LV+septum) ratio, near-resistance pulmonary artery agonist-induced force, and endothelium-dependent and independent relaxation. The lung biopterin content was inversely related to age for both types, but significantly lower in hph-1 mice, compared to wild-type animals. As judged by the RV/LV+septum ratio, newborn hph-1 mice have pulmonary hypertension and, after a 2-week 13% oxygen exposure, the ratios were similar in both types. The pulmonary arterial agonist-induced force was reduced (P<0.01) in hph-1 animals and no type-dependent difference in endothelium-dependent or independent vasorelaxation was observed. Compared to wild-type mice, the lung H(2)O(2) content was increased, whereas the eNOS expression was decreased (P<0.01) in hph-1 animals. The pulmonary arterial medial thickness, a surrogate marker of vascular remodeling, was increased (P<0.01) in hph-1 compared to wild type mice. In conclusion, our data suggest that pulmonary hypertension is present from birth in the GTPCH1-deficient mice, not as a result of impaired vasodilation, but secondary to vascular remodeling. PMID- 21982897 TI - Influence of formulation variables on the biodistribution of multifunctional block copolymer micelles. AB - The physico-chemical characteristics and composition of block copolymer micelles (BCMs) may influence the pharmacokinetics and consequently, the desired delivery characteristics. In this study the influence of formulation variables such as size, density of targeting ligand [i.e. epidermal growth factor (hEGF)] and the bifunctional chelator (BFC) used for labelling the BCMs with (111)In, on the pharmacokinetics and biodistribution in mice were evaluated. BCMs were prepared from Me-PEG(x)-b-PCL(y) (x=2.5 k, y=1.2 k for 15 nm BCMs and x=5 k, y=5 k for 60 nm BCMs) with (targeted, 1 or 5 mol% hEGF) or without (non-targeted) hEGF-PEG(x) b-PCL(y). To investigate the effect of the BFC on the pharmacokinetics, the BCMs were labelled with (111)In using p-SCN-Bn-DOTA (Bn-DOTA-PEG(x)-b-PCL(y)), H(2)N DOTA (DOTA-PEG(x)-b-PCL(y)), DTPA anhydride (DTPA-PEG(x)-b-PCL(y)) or p-SCN-Bn DTPA (Bn-DTPA-PEG(x)-b-PCL(y)). The resulting 15 nm or 60 nm non-targeted or targeted (1 or 5 mol% hEGF) were injected via a tail vein to mice bearing MDA-MB 468 human breast cancer xenograft that overexpress EGFR, followed by pharmacokinetics and biodistribution studies. Pharmacokinetic parameters were determined by fitting the blood concentration vs time data using a two compartment model with i.v. bolus input. Pharmacokinetic parameters were found to depend on BCM size, the BFC used as well as the density of hEGF on the surface of the BCMs. BCMs labelled with p-SCN-Bn-DTPA ((111)In-Bn-BCMs) showed improved pharmacokinetics (i.e. extended circulation lifetime) and tumor uptake compared to those labelled with DOTA-PEG(x)-b-PCL(y), p-SCN-Bn-DOTA or DTPA dianhydride. Formulations with a high density of hEGF (5 mol% hEGF) had short circulation half lives. BCMs labelled with (111)In via p-SCN-Bn-DTPA showed highest accumulation in the liver and spleen and slower whole body elimination. Smaller sized BCMs were rapidly cleared from the circulation. Increasing the density of hEGF on the surface did not improve tumor uptake due to faster clearance from the circulation. To achieve improved pharmacokinetics and in turn effective exploitation of the EPR effect, p-SCN-Bn-DTPA emerged as the optimal BFC for radiolabelling BCMs while a lower density of hEGF gave more favourable organ distribution. PMID- 21982898 TI - Improved in vivo delivery of m-THPC via pegylated liposomes for use in photodynamic therapy. AB - Pegylated liposomal nanocarriers have been developed with the aim of achieving improved uptake of the clinical PDT photosensitiser, m-THPC, into target tissues through increased circulation time and bioavailability. This study investigates the biodistribution and PDT efficacy of m-THPC in its standard formulation (Foscan(r)) compared to m-THPC incorporated in liposomes with different degrees of pegylation (FosPEG 2% and FosPEG 8%), following i.v. administration to normal and tumour bearing rats. The plasma pharmacokinetics were described using a three compartmental analysis and gave elimination half lives of 90 h, 99 h and 138 h for Foscan(r), FosPEG 2% and 8% respectively. The accumulation of m-THPC in tumour and normal tissues, including skin, showed that maximal tumour to skin ratios were observed at <= 24 h with FosPEG 2% and 8%, whilst skin photosensitivity studies showed Foscan(r) induces more damage compared to the liposomes at drug-light intervals of 96 and 168 h. PDT treatment at 24h post administration (0.05 mg kg-1) showed higher tumour necrosis using pegylated liposomal formulations in comparison to Foscan(r), which is attributed to the higher tumour uptake and blood plasma concentrations. Clinically, this improved selectivity has the potential to reduce not only normal tissue damage, but the drug dose required and cutaneous photosensitivity. PMID- 21982899 TI - Propellant-based inhalers for the non-invasive delivery of genes via oral inhalation. AB - In this work we describe the development of a propellant-based, portable oral inhalation platform for the pulmonary delivery of genes. A core-shell strategy is utilized to efficiently disperse cationic-polymer-DNA nanoparticles in hydrofluoroalkane propellants, and to generate aerosols from the corresponding pressurized metered-dose inhaler formulations (pMDIs) that have excellent aerosol characteristics, suitable for deep lung deposition. The engineered polyplexes and core-shell structures were fully characterized, and their ability to transfect model lung alveolar epithelium cells in vitro was demonstrated. We also show that the propellant does not affect the biological activity of the plasmid DNA, and that the core-shell formulations have no in vitro cytotoxicity. The relevance of this work stems from the fact that pMDIs are the least expensive and most widely used portable oral inhalation devices, and are thus promising platforms for targeting genes to the lungs for the treatment of medically relevant diseases including asthma, cystic fibrosis, chronic obstructive pulmonary disease, and lung cancer. PMID- 21982900 TI - Sustained in vivo release from imprinted therapeutic contact lenses. AB - In this paper, we demonstrate the successful in vivo extended release of a small molecular weight therapeutic, ketotifen fumarate (MW=425), from molecularly imprinted, therapeutic contact lenses. This is the first time that a steady, effective concentration of drug is maintained in the tear film from a contact lens for an extended period of time for the entire duration of lens wear. Poly(HEMA-co-AA-co-AM-co-NVP-co-PEG200DMA) soft contact lenses were prepared (100+/-5 MUm thickness, diameter 11.8 mm, power zero), and a constant tear film concentration of 170+/-30 MUg/mL was measured for up to 26 hrs in a New Zealand white rabbit model. The results showed a dramatic increase in ketotifen mean residence time (MRT) and bioavailability compared to topical drop therapy and drug soaked lenses. The MRT for imprinted lenses was 12.47+/-3.99 hrs, ~4 and 50 fold greater than non-imprinted lenses and 0.035% eye drops (Zaditor(r)), respectively. Furthermore, AUC(0-26 hrs) was 9 and 94 fold greater for imprinted lenses than non-imprinted lenses and eye drops, respectively. The results indicate that molecular imprinting provides an exciting rational engineering strategy for sustained release. It is clear that imprinted lenses are very promising combination devices and are much more effective and efficient delivery devices than eye drops. PMID- 21982901 TI - Efficient CRM197-mediated drug targeting to monocytes. AB - Efficient delivery of drugs to specific cellular reservoirs is of particular importance for therapeutics that are not able to pass cellular barriers and that may have unwanted side effects in off-target tissues. Heparin-binding epidermal growth factor (HB-EGF) is expressed on leukocytes and may be targeted for specific drug delivery using cross-reacting material (CRM)197, a non-toxic variant of diphtheria toxin and exogenous substrate for HB-EGF. We used fluorescently labeled CRM197 and CRM197-coated liposomes to investigate their potential use for drug delivery to leukocytes. We demonstrate that CRM197-guided systems are efficiently taken up by human leukocytes in vitro. CRM197 was also found to specifically target leukocytes in vivo in mice with components of the human immune system (HIS mice) and hamsters. Monocytes represent the most prominent subset of leukocytes that showed highly specific CRM197-mediated uptake. We therefore propose the application of CRM197 as a novel targeting approach in diseases that require the selective treatment of monocytes. PMID- 21982902 TI - Ultrasound-induced cavitation enhances the delivery and therapeutic efficacy of an oncolytic virus in an in vitro model. AB - We investigated whether ultrasound-induced cavitation at 0.5 MHz could improve the extravasation and distribution of a potent breast cancer-selective oncolytic adenovirus, AdEHE2F-Luc, to tumour regions that are remote from blood vessels. We developed a novel tumour-mimicking model consisting of a gel matrix containing human breast cancer cells traversed by a fluid channel simulating a tumour blood vessel, through which the virus and microbubbles could be made to flow. Ultrasonic pressures were chosen to maximize either broadband emissions, associated with inertial cavitation, or ultraharmonic emissions, associated with stable cavitation, while varying duty cycle to keep the total acoustic energy delivered constant for comparison across exposures. None of the exposure conditions tested affected cell viability in the absence of the adenovirus. When AdEHE2F-Luc was delivered via the vessel, inertial cavitation increased transgene expression in tumour cells by up to 200 times. This increase was not observed in the absence of Coxsackie and Adenovirus Receptor cell expression, discounting sonoporation as the mechanism of action. In the presence of inertial cavitation, AdEHE2F-Luc distribution was greatly improved in the matrix surrounding the vessel, particularly in the direction of the ultrasound beam; this enabled AdEHE2F-Luc to kill up to 80% of cancer cells within the ultrasound focal volume in the gel 24 hours after delivery, compared to 0% in the absence of cavitation. PMID- 21982903 TI - Preparation of polymer-based multimodal imaging agent to visualize the process of bone regeneration. AB - The objective of this study is to design a new multimodal imaging system for the evaluation of bone regeneration process. Pamidronate (PA) of bisphosphonates with a high affinity for hydroxyapatite, was introduced to pullulan with different molecular weights (PA-pullulan). Then, two probes for fluorescence and magnetic resonance (MR) imagings were introduced into the PA-pullulan to prepare the PA pullulan conjugates containing both the imaging probes (PA-pullulan-F/M). The PA pullulan-F/M conjugates had an affinity for hydroxyapatite. A gelatin hydrogel incorporating bone morphogentic protein (BMP)-2 was prepared and implanted subcutaneously into mice to obtain an animal model of bone regeneration. When intravenously injected into mice with the bone tissue ectopically formed by the BMP-2-incorporated hydrogel to fluorescently evaluate their body distribution, the PA-pullulan-F/M conjugates were accumulated in the bone tissue regenerated. The time profile of fluorescent intensity well corresponded with that of calcium amount in the bone tissue newly formed. In addition, the PA-pullulan-F/M conjugates showed an MR ability similar to Gd-DTPA (gadopentetate dimeglumine) of a MR imaging agent clinically used. The MR signal around the bone tissue newly formed was enhanced for mice injected with PA-pullulan-F/M prepared from pullulan with the molecular weight of 6000. It is concluded that the PA-pullulan-F/M conjugate is a useful multimodal agent of polymeric delivery system to evaluate the process of bone regeneration. PMID- 21982904 TI - Uptake mechanisms of non-viral gene delivery. AB - Non-viral gene delivery is currently a hot subject for its relative safety and simplicity of use; however, it is still far from being ideal enough to be clinically used for its comparatively lower efficiency than viral gene delivery. To improve the efficiency of non-viral gene delivery needs a comprehensive understanding of the uptake mechanisms. Macromolecules are internalized into cells by a variety of mechanisms, and their intracellular fates are usually relevant with the uptake pathways. The uptake pathways of non-viral gene complexes are usually determined by not only the gene/carrier interaction but also by the interaction between complexes and target cells. The best characterized uptake pathway is the so-called clathrin-mediated endocytic pathway. However, there are numerous updates of knowledge about endocytic pathways and even non-endocytic pathways in recent years with the development of novel technologies for tracking and inhibiting. In this review, we will try to sort out our current understanding of the uptake mechanisms of non-viral gene delivery. In addition, factors for pathway selection are summarized in the third section. Finally, the useful inhibitors or tools for the study of these pathways will also be concluded in the last section. PMID- 21982905 TI - A validated LC-MS/MS assay for the simultaneous determination of the anti leukemic agent dasatinib and two pharmacologically active metabolites in human plasma: application to a clinical pharmacokinetic study. AB - Dasatinib (Sprycel) is a potent antitumor agent prescribed for patients with chronic myeloid leukemia (CML). To enable reliable quantification of dasatinib and its pharmacologically active metabolites in human plasma during clinical testing, a sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated. Samples were prepared using solid phase extraction on Oasis HLB 96-well plates. Chromatographic separation was achieved isocratically on a Luna phenyl-hexyl analytical column. Analytes and the stable labeled internal standards were detected by positive ion electrospray tandem mass spectrometry. The assay was validated over a concentration range of 1.00-1000 ng/mL for dasatinib and its two active metabolites. Intra- and inter assay precision values for replicate QC control samples were within 5.3% for all analytes during the assay validation. Mean QC control accuracy values were within +/- 9.0% of nominal values for all analytes. Assay recoveries were high (>79%) and internal standard normalized matrix effects were minimal. The three analytes were stable in human plasma for at least 22 h at room temperature, for at least 123 days at -20 degrees C, and following at least six freeze-thaw cycles. The validated method was successfully applied to the quantification of dasatinib and two active metabolites in a human pharmacokinetic study. PMID- 21982906 TI - Diabetes mellitus and risk of subsequent depression: a longitudinal study. AB - BACKGROUND: Findings of previous studies on the association between diabetes and the risk of depression are contradictory. Furthermore, much less is known concerning the association among young adults. OBJECTIVE: To investigate whether diabetes is associated with an increased risk of subsequent development of depression, with emphasis on age-specific variations. DESIGN: A cohort study. SETTING: Claims data of one million subjects randomly selected from 23 million people covered by the Taiwan National Health Insurance program. PARTICIPANTS: From the claims data, we identified 14,048 patients aged >= 20 years with newly diagnosed diabetes in 2000-2002 and randomly selected 55,608 non-diabetic subjects for comparison, that were frequency-matched by calendar year, age, and gender. Incidence rates of depression to the end of 2007 were identified, and risks were compared between the two groups. RESULTS: The incidence of depression was 1.80-times higher in the diabetic group than in nondiabetic subjects over a median follow-up of 6.5 years (adjusted hazard ratio [HR]=1.46, 95% confidence interval [CI]: 1.24-1.71). Age-specific HRs for incidence of depression in relation to diabetes were not statistically different between the patient subgroups aged 20-39, 40-49, 50-59, 60-69 and >= 70 years (p value for age diabetes interaction=0.33). Stratified analyses showed that the association was much stronger for subjects without comorbid cardiovascular disease than for those with this comorbidity. Insulin treatment was associated with a 43% reduced risk of depression in diabetic patients. CONCLUSIONS: In this population-based study, diabetic patients were at a higher risk for subsequent depression. Adequate treatment reduced the risk. PMID- 21982907 TI - What is a nursing research journal? PMID- 21982908 TI - Clinical outcomes of facial transplantation: a review. AB - A total of 18 composite tissue allotransplants of the face have currently been reported. Prior to the start of the face transplant programme, there had been intense debate over the risks and benefits of performing this experimental surgery. This review examines the surgical, functional and aesthetic, immunological and psychological outcomes of facial transplantation thus far, based on the predicted risks outlined in early publications from teams around the world. The initial experience has demonstrated that facial transplantation is surgically feasible. Functional and aesthetic outcomes have been very encouraging with good motor and sensory recovery and improvements to important facial functions observed. Episodes of acute rejection have been common, as predicted, but easily controlled with increases in systemic immunosuppression. Psychological improvements have been remarkable and have resulted in the reintegration of patients into the outside world, social networks and even the workplace. Complications of immunosuppression and patient mortality have been observed in the initial series. These have highlighted rigorous patient selection as the key predictor of success. The overall early outcomes of the face transplant programme have been generally more positive than many predicted. This initial success is testament to the robust approach of teams. Dissemination of outcomes and ongoing refinement of the process may allow facial transplantation to eventually become a first-line reconstructive option for those with extensive facial disfigurements. PMID- 21982909 TI - Synthesis of imprinted beads by aqueous suspension polymerisation for chiral recognition of antihistamines. AB - A novel non-stabilised aqueous suspension polymerisation methodology for the preparation of spherical molecularly imprinted polymers is described with chlorpheniramine (CP), d-chlorpheniramine (d-CP), brompheniramine (BP) and d brompheniramine (d-BP) as the templates, respectively. Using this rapid and simple technique, controlled polymer beads in the low micron range with narrow size distributions were generated by photo-polymerisation. The use of agitation speed as a method of controlling bead size distribution was demonstrated. Enantioselective properties of the imprinted beads were examined and the polymers prepared using d-chlorpheniramine and d-brompheniramine were capable of discriminating between the enantiomers of the template. Cross-selectivity studies were performed by batch rebinding with the influence of template size and functional group orientation of analytes on the recognition properties of the imprinted polymers investigated. Physical characteristics of all polymers were studied by nitrogen sorption porosimetry, particle size analysis and scanning electron microscopy (SEM) in order to gain an insight into the role of such properties on retention behaviour. PMID- 21982910 TI - Rapid and simple one-step membrane extraction for the determination of 8-hydroxy 2'-deoxyguanosine in human plasma by a combination of on-line solid phase extraction and LC-MS/MS. AB - A quantitative analytical method using automated on-line solid phase extraction (SPE) and liquid chromatography-electrospray tandem mass spectrometry (LC-ESI MS/MS) for the determination of 8-OHdG (8-hydroxy-2'-deoxyguanosine) in human plasma was developed and validated. A one-step membrane extraction method for the plasma sample preparation and a C18 SPE column with simple extraction and purification were used for the on-line extraction. A C18 column was employed for LC separation and ESI-MS/MS was utilized for detection. (15)N(5)-8-OHdG ((15)N(5) 8-hydroxy-2'-deoxyguanosine) was used as an internal standard for quantitative determination. The extraction, clean-up and analysis procedures were controlled by a fully automated six-port switch valve as one strategy to reduce the matrix effect and simultaneously improve detection sensitivity. Identification and quantification were based on the following transitions: m/z 284->168 for 8-OHdG and m/z 289->173 for (15)N(5)-8-OHdG. Satisfactory recovery was obtained, and the recovery ranged from 95.1 to 106.1% at trace levels in human plasma and urine, with a CV lower than 5.4%. Values for intraday and interday precision were between 2.3 and 6.8% for plasma and between 2.7 and 4.5% for urine, respectively. Values for the method accuracy of intraday and interday assays ranged from 93.0 and 100.5% for plasma and 110.2 and 119.4% for urine, respectively. The limits of detection (LOD) and LOQ were 0.008 ng/mL and 0.02 ng/mL, respectively.The applicability of this newly developed method was demonstrated by analysis of human plasma samples for an evaluation of the future risk of oxidative stress status in human exposure to nanoparticles and other diseases. PMID- 21982911 TI - Determination of four pyridine alkaloids from Tripterygium wilfordii Hook. f. in human plasma by high-performance liquid chromatography coupled with mass spectrometry. AB - A novel liquid chromatography-atmospheric-pressure chemical ionization-mass spectrometry (LC-APCI/MS) method was developed and validated for the simultaneous determination of four sesquiterpene pyridine alkaloids (wilfortrine, wilfordine, wilforgine and wilforine) in human plasma. The chromatographic separation was performed on a Shim-pack XR-ODS column using an ammonium acetate buffer solution acetonitrile in a gradient program. The detection was achieved by an ion trap mass spectrometry in the positive selected ion monitoring (SIM) mode. The method utilized acetonitrile as protein precipitation solvent and followed by solid phase extraction (SPE). Calibration curves were linear for the four alkaloids over the range of 0.5-100.0 MUg/L with the limits of quantification of 0.5 MUg/L, while the method exhibited the recovery of 86.5-98.6%, intra- and inter-day RSDs of less than 8.2% and 12.8%, respectively. Methodology was validated in line with the EU requirements (Commission Decision 2002/657/EC). Results of incurred samples demonstrated excellent reproducibility. To our knowledge, this is the first analytical method for simultaneous determination of the four sesquiterpene pyridine alkaloids in plasma. The method was applicable to clinical pharmaceutical research of alkaloids in rheumatoid arthritis volunteer patients after oral administrations. PMID- 21982912 TI - Impact of lysine-affinity chromatography on supercoiled plasmid DNA purification. AB - Gene therapy and DNA vaccination cover a variety of applications using viral and non-viral vectors as vehicles of choice for treatment of genetic or acquired diseases. Recently, most therapeutic applications have been performed with non viral biological agents preparations highly enriched in supercoiled plasmid molecules and it has been concluded that this isoform is more efficient at gene transfection than open circular isoform. This work describes for the first time a new strategy that uses lysine-chromatography to efficiently eliminate Escherichia coli impurities as well as other ineffective plasmid isoforms present in a complex clarified lysate to purify and obtain pharmaceutical-grade supercoiled plasmid DNA. The quality control tests indicated that the levels of impurities in the final plasmid product were below the generally accepted specifications. Furthermore, the delivery of the purified product to eukaryotic cells, the cell uptake and transfection efficiency were also analyzed. The results showed that the transfection efficiency reached with the application of the supercoiled plasmid conformation, purified with lysine-agarose, was higher than the values achieved for other plasmid topologies. Therefore, this study presents a new enabling technology to obtain the completely purified non-viral vector, able to act with good efficiency as gene therapy delivery vehicle in several diseases like cancer. PMID- 21982913 TI - The development of an optimized sample preparation for trace level detection of 17alpha-ethinylestradiol and estrone in whole fish tissue. AB - The purpose of this study was to develop an optimized method for the extraction and determination of 17alpha-ethinylestradiol (EE2) and estrone (E1) in whole fish tissues at ng/g levels. The optimized procedure for sample preparation includes extraction of tissue by accelerated solvent extraction (ASE-200), lipid removal by gel permeation chromatography (GPC), and a cleanup step by acetonitrile precipitation followed by a hexane wash. Analysis was performed by gas chromatography/mass spectrometry (GC/MS) in negative chemical ionization (NCI) mode after samples were derivatized with pentafluorobenzoyl chloride (PFBCl). The method was developed using high lipid content wild fish that were exposed to the tested analytes. The whole procedure recoveries ranged from 74.5 to 93.7% with relative standard deviation (RSD) of 2.3-6.2% for EE2 and 64.8 to 91.6% with RSD of 9.46-0.18% for E1. The method detection limits were 0.67 ng/g for EE2 and 0.68 ng/g for E1 dry weight. The method was applied to determine EE2 levels in male goldfish (Carrasius auratus) after a 72 h dietary exposure. All samples contained EE2 averaging 1.7ng/g (+/-0.29 standard deviation, n=5). This is the first optimized protocol for EE2 extraction from whole fish tissue at environmentally relevant concentrations. Due to high sensitivity and recovery, the developed method will improve our knowledge about the environmental fate and uptake of synthetic steroidal estrogens in fish populations. PMID- 21982914 TI - [Scarring alopecia]. AB - Scarring alopecia refers to a group of disorders of various etiologies that cause permanent hair loss. In this article, we focus on primary cicatricial alopecia, a group of diseases in which the hair follicle is the main target of the inflammatory process. These disorders are currently classified as lymphocytic, neutrophilic, or mixed according to the cells that make up the inflammatory infiltrate. The pathogenesis of the majority of these conditions is not fully understood and they may have similar clinical features, often making it necessary to perform 1 or more skin biopsies in order to reach a diagnosis. Management depends on early and accurate diagnosis and aggressive treatment in some cases in order to prevent follicular destruction and scarring. PMID- 21982915 TI - Comparative study of a new quantitative rapid test with an established ELISA method for faecal calprotectin. PMID- 21982916 TI - Quantification of p38alphaMAP kinase: a prognostic marker in HNSCC with respect to radiation therapy. AB - BACKGROUND: Translation of early findings from basic research is aimed to benefit cancer therapeutics. We report the p38alpha level in serum of head and neck squamous cell carcinoma (HNSCC) patients indicating it as a prognostic marker and established its correlation with radiation therapy (RT). METHODS: The case controlled study was performed on 120 HNSCC patients from whom 81 patients and 45 controls were statistically analyzed. The p38alpha estimation was done at pre-RT, during-RT and post-RT using a real time Surface Plasmon Resonance (SPR) technology, ELISA and western blot. RESULTS: HNSCC patients showed threefold increase in p38alpha level when compared to control (p value<0.0001). The estimated concentration of p38alpha in a temporal manner, before-RT, during-RT and post-RT was 0.61 ng/MUl (95%CI: 0.53-0.69), 0.35 ng/MUl (95%CI: 0.31-0.38) and 0.30 ng/MUl (95%CI: 0.26-0.33), respectively. Among the 81 cases, 70 patients (86.42%) showed a declined p38alpha in response to RT as evaluated by SPR and were responding clinically (clinical tumor regression). CONCLUSIONS: This study showed elevated p38alpha level at cancer diagnosis and a statistically significant decline during-RT and post-RT periods. Hence, it can emerge as a prognostic marker supporting the candidature of p38alpha as a suitable serum marker in HNSCC. PMID- 21982917 TI - Perinatal asphyxia: kidney failure does not affect S100B urine concentrations. AB - BACKGROUND: S100B protein is a well-established marker of brain damage. Its importance in urine assessment is the convenience of a collection and sampling procedure that can be repeated without risk for the newborn. Since S100B is mainly eliminated by the kidneys and perinatal asphyxia (PA) is often associated with kidney failure we investigated whether S100B release might be kidney mediated, thereby modifying the protein's reliability as a brain-damage marker. METHODS: We examined a cohort of healthy (n=432) and asphyxiated newborns (n=32) in whom kidney function parameters (blood urea and creatinine concentrations and urine gravity) and urine S100B concentrations were assessed in the first hours after birth. Data were analyzed by multiple logistic regression analysis with S100B as independent variable among a variety of clinical and laboratory monitoring parameters. RESULTS: S100B urine concentrations were significantly higher (P<0.01) in PA newborns than controls. No significant correlations (P>0.05, for all) between total urine S100B levels and kidney function parameters such as creatinine (r=0.03), urea (r=0.04) and urine gravity (r=0.06) were found. Multiple logistic regression analysis of a series of clinical and laboratory monitoring parameters (odds ratio at sampling: 9.47) with S100B as independent variable showed a positive significant correlation only between S100B levels (P<0.001) and the occurrence of PA. CONCLUSION: The present study shows that altered kidney function is not an adverse and/or confounding factor in urine S100B assessment and marks a new step towards the introduction of longitudinal monitoring of brain constituents in clinical practice. PMID- 21982918 TI - Activation of GABAA or 5HT1A receptors in the raphe pallidus abolish the cardiovascular responses to exogenous stress in conscious rats. AB - Dysfunction in serotonin (5HT) neurotransmission in the brainstem of infants may disrupt protective responses to stress and increase the risk for Sudden Infant Death Syndrome (SIDS). The raphe pallidus (NRP) and other brainstem nuclei are rich in 5HT and are thought to mediate stress responses, including increases in blood pressure (BP) and heart rate (HR). Determining how 5HT neurotransmission in the brainstem mediates responses to stress will help to explain how dysfunction in neurotransmission could increase the risk of SIDS. It was hypothesized that alterations in neurotransmission in the NRP, specifically activation of the 5HT(1A) receptor subtype, would block cardiovascular responses to various types of exogenous stress. Using aseptic techniques, male Sprague-Dawley rats were instrumented with radiotelemetry probes which enabled non-invasive measurement of BP and HR. An indwelling microinjection cannula was also stereotaxically implanted into the NRP for injection of drugs that altered local 5HT neurotransmission. Following a one week recovery period, rats were microinjected with either muscimol (GABA(A) receptor agonist), 8-OH-DPAT (agonist to the inhibitory 5HT(1A) receptor), or a vehicle control (artificial cerebral spinal fluid; ACSF) immediately prior to exposure to one of three stressors: handling, air jet, or restraint. Physical handling and restraint of the animal were designed to elicit a mild and a maximal stress response respectively; while an air jet directed at the rat's face was used to provoke a psychological stress that did not require physical contact. All three stressors elicited similar and significant elevations in HR and BP following ACSF that persisted for at least 15 min with BP and HR elevated by ~14.0 mmHg and ~56.3 bpm respectively. The similarity in the stress responses suggest even mild handling of a rat elicits a maximal sympathoexcitatory response. The stress response was abolished following 8-OH-DPAT or muscimol microinjection suggesting the cardiovascular responses to stress are mediated by the NRP and likely involve the 5HT(1A) receptor. Impairment in 5HT(1A) receptor function in the NRP likely impairs the normal cardioprotective responses to stress and may contribute to the etiology of SIDS. PMID- 21982920 TI - Mechanism of the aromatic aminotransferase encoded by the Aro8 gene from Saccharomyces cerevisiae. AB - The amino acid L-lysine is synthesized in Saccharomyces cerevisiae via the alpha aminoadipate pathway. An as yet unidentified PLP-containing aminotransferase is thought to catalyze the formation of alpha-aminoadipate from alpha-ketoadipate in the L-lysine biosynthetic pathway that could be the yeast Aro8 gene product. A screen of several different amino acids and keto-acids showed that the enzyme uses L-tyrosine, L-phenylalanine, alpha-ketoadipate, and L-alpha-aminoadipate as substrates. The UV-visible spectrum of the aminotransferase exhibits maxima at 280 and 343 nm at pH 7.5. As the pH is decreased the peak at 343 nm (the unprotonated internal aldimine) disappears and two new peaks at 328 and 400 nm are observed representing the enolimine and ketoenamine tautomers of the protonated aldimine, respectively. Addition, at pH 7.1, of alpha-ketoadipate to free enzyme leads to disappearance of the absorbance at 343 nm and appearance of peaks at 328 and 424 nm. The V/E(t) and V/K(alpha-ketoadipate)E(t) pH profiles are pH independent from pH 6.5 to 9.6, while the V/K(L-tyrosine) pH-rate profile decreases below a single pK(a) of 7.0 +/- 0.1. Data suggest the active enzyme form is with the internal aldimine unprotonated. We conclude the enzyme should be categorized as a alpha-aminoadipate aminotransferase. PMID- 21982919 TI - Manipulating substrate and pH in zymography protocols selectively distinguishes cathepsins K, L, S, and V activity in cells and tissues. AB - Cathepsins K, L, S, and V are cysteine proteases that have been implicated in tissue-destructive diseases such as atherosclerosis, tumor metastasis, and osteoporosis. Among these four cathepsins are the most powerful human collagenases and elastases, and they share 60% sequence homology. Proper quantification of mature, active cathepsins has been confounded by inhibitor and reporter substrate cross-reactivity, but is necessary to develop properly dosed therapeutic applications. Here, we detail a method of multiplex cathepsin zymography to detect and distinguish the activity of mature cathepsins K, L, S, and V by exploiting differences in individual cathepsin substrate preferences, pH effects, and electrophoretic mobility under non-reducing conditions. Specific identification of cathepsins K, L, S, and V in one cell/tissue extract was obtained with cathepsin K (37 kDa), V (35 kDa), S (25 kDa), and L (20 kDa) under non-reducing conditions. Cathepsin K activity disappeared and V remained when incubated at pH 4 instead of 6. Application of this antibody free, species independent, and medium-throughput method was demonstrated with primary human monocyte-derived macrophages and osteoclasts, endothelial cells stimulated with inflammatory cytokines, and normal and cancer lung tissues, which identified elevated cathepsin V in lung cancer. PMID- 21982921 TI - Energetics of small hydrogen-vacancy clusters in bcc iron. AB - Hydrogen may be trapped in voids in iron, leading to undesirable material properties. In this paper, the energetics of small hydrogen-vacancy clusters in body centered cubic iron are investigated. Results from two interatomic potentials are compared. We use molecular dynamics and Monte Carlo methods to find the minimum energy configurations of voids of up to ten vacancies containing up to 50 hydrogen atoms with ratios of hydrogen to vacancy of 10 or less. The formation energies and binding energies of defects to these clusters are calculated. Our results indicate that the hydrogen stabilizes bubbles by causing vacancies to be more tightly bound to clusters, while neighboring irons are less tightly bound. Hydrogen itself becomes less well bound to clusters as the inventory increases. The more physically relevant potential indicates a maximum supported ratio of hydrogen atoms to vacancies of about 4. PMID- 21982923 TI - Video analysis of dispatcher-rescuer teamwork-Effects on CPR technique and performance. AB - OBJECTIVE: We wanted to study the effect of continuous dispatcher communication on CPR technique and performance during 10min of simulated cardiac arrest. METHOD: We reviewed video recordings and manikin data from 30 CPR trained lay people who where left alone in a simulated cardiac arrest situation with a manikin in a home-like environment (in a small, confined kitchen with the disturbing noise of a radio). CPR was performed for 10min with continuous telephone instructions via speaker function from a dispatcher. The dispatcher was blinded for CPR performance and video. Dispatcher communication, compression technique and ventilation technique was scored as accomplished or failed in the 1st and 10th minute. RESULTS: 29/30 rescuers were able to hear instructions, answer questions from the dispatcher and perform CPR in parallel. Rescuer position beside manikin was initially correct for 13/30, improving to 21/30 (p=0.008). Compression technique was adequate for the whole episode, with an insignificant trend for improvement; 29 to 30/30 using straight arms, 28 to 30/30 in a vertical position over chest and 24 to 27/30 counting loudly. 17/29 placed their hands between the nipples initially, improving to 24/29 (p=0.065). Mean compression rate improved from 84 to 101min(-1) (p<0.001), and compression depth maintained adequate (43 to 42mm). Initially, 17/29 used chin-lift manoeuvre, 14/30 used head-tilt and 19/29 used nose pinch to manage open airways, compared to 18, 20 and 22/29 (ns) in the 10th minute, respectively. Successful delivery of ventilation improved from 13/30 to 23/30 (p=0.006). CONCLUSION: Bystander and dispatcher can communicate successfully during ongoing CPR using a telephone with speaker function. CPR technique and quality improved or did not change over 10min with continuous dispatcher assistance. These results suggest a potential for improved bystander CPR using rescuer-dispatcher teamwork. PMID- 21982924 TI - Initial treatment of acute coronary syndromes. Is there a future for MONA acronym after the 2010 guidelines? PMID- 21982925 TI - Distinct mechanisms of DNA repair in mycobacteria and their implications in attenuation of the pathogen growth. AB - About a third of the human population is estimated to be infected with Mycobacterium tuberculosis. Emergence of drug resistant strains and the protracted treatment strategies have compelled the scientific community to identify newer drug targets, and to develop newer vaccines. In the host macrophages, the bacterium survives within an environment rich in reactive nitrogen and oxygen species capable of damaging its genome. Therefore, for its successful persistence in the host, the pathogen must need robust DNA repair mechanisms. Analysis of M. tuberculosis genome sequence revealed that it lacks mismatch repair pathway suggesting a greater role for other DNA repair pathways such as the nucleotide excision repair, and base excision repair pathways. In this article, we summarize the outcome of research involving these two repair pathways in mycobacteria focusing primarily on our own efforts. Our findings, using Mycobacterium smegmatis model, suggest that deficiency of various DNA repair functions in single or in combinations severely compromises their DNA repair capacity and attenuates their growth under conditions typically encountered in macrophages. PMID- 21982926 TI - Lamin A/C deficiency is associated with fat infiltration of muscle and bone. AB - Sarcopenia and osteopenia are two common components of the frailty syndrome that may share a common underlying mechanism. Since frailty has been associated with increased fat infiltration in muscle and bone, we hypothesized that lamin A/C, a protein of the nuclear envelope that regulates adipose differentiation, could be associated with the pathophysiology of both osteo and sarcopenia in the frailty syndrome. Four-week-old lamin A/C null (Lmna(-/-)), heterozygous (Lmna(+/-)) and wild type (WT) mice were sacrificed and their mid-thigh analyzed for fat infiltration using invasive (histology) and non-invasive (MUCT) methods. Lmna(-/ ) mice showed a significant increase in inter- (~4-fold) and intra-myofiber (~2.5 fold) fat and marrow fat infiltration (~40-fold), with a significant decrease in muscle volume (-42.8%) and bone volume (-21.8%), as compared with WT controls. Furthermore, fat infiltration happened concomitantly with a significant decline in muscle and bone strength in Lmna(-/-) mice. From a mechanistic approach, high levels of pro-adipogenic factors PPARgamma and C/EBPalpha were associated with a reduction in myogenic and osteogenic factors from the Wnt-10b/beta-catenin signalling pathway in Lmna(-/-) mice. In conclusion, lamin A/C could constitute the determinant factor in the pathogenesis and potential treatment of both sarcopenia and osteopenia, which are commonly observed in the frailty syndrome. PMID- 21982927 TI - Measurement of bacterial volume by transmission-through-dye imaging. AB - Transmission-through-dye (TTD) microscopy makes possible direct measurement of bacterial volume, irrespective of cell shape. The technique can be realized on any brightfield microscope and is applicable to bacteria of all shapes. TTD imaging requires that intact bacteria be immobilized on a flat transparent surface, such as a glass coverslip. PMID- 21982928 TI - Neurovascular coupling is brain region-dependent. AB - Despite recent advances in alternative brain imaging technologies, functional magnetic resonance imaging (fMRI) remains the workhorse for both medical diagnosis and primary research. Indeed, the number of research articles that utilise fMRI have continued to rise unabated since its conception in 1991, despite the limitation that recorded signals originate from the cerebral vasculature rather than neural tissue. Consequently, understanding the relationship between brain activity and the resultant changes in metabolism and blood flow (neurovascular coupling) remains a vital area of research. In the past, technical constraints have restricted investigations of neurovascular coupling to cortical sites and have led to the assumption that coupling in non cortical structures is the same as in the cortex, despite the lack of any evidence. The current study investigated neurovascular coupling in the rat using whole-brain blood oxygenation level-dependent (BOLD) fMRI and multi-channel electrophysiological recordings and measured the response to a sensory stimulus as it proceeded through brainstem, thalamic and cortical processing sites - the so-called whisker-to-barrel pathway. We found marked regional differences in the amplitude of BOLD activation in the pathway and non-linear neurovascular coupling relationships in non-cortical sites. The findings have important implications for studies that use functional brain imaging to investigate sub-cortical function and caution against the use of simple, linear mapping of imaging signals onto neural activity. PMID- 21982929 TI - A geometric view of global signal confounds in resting-state functional MRI. AB - Resting-state functional magnetic resonance imaging (fMRI) is proving to be an effective tool for mapping the long-range functional connections of the brain in both health and disease. One of the primary measures of connectivity is the correlation between the blood oxygenation level dependent (BOLD) time series observed in different brain regions. The computation of the correlation is often dominated by the presence of a strong global component that can introduce significant variability across functional connectivity maps acquired from different experimental scans or subjects. To address this issue, a variety of global signal correction methods have been proposed, but there is currently a lack of a clear consensus on the best approach to use. Furthermore, there has been concern that some global signal correction methods, such as global signal regression, may produce significant negative bias in the correlation values. In this paper we introduce a framework for visualizing the signal structure of resting-state fMRI data and characterizing the properties of the global signal. Using this framework, we demonstrate that a portion of the global signal can be viewed as an additive confound that increases with the mean BOLD amplitude. An approach for minimizing the contribution of this additive confound is presented, and an initial comparison with existing global signal correction methods is provided. PMID- 21982930 TI - Nothing to lose: processing blindness to potential losses drives thrill and adventure seekers. AB - Sensation seeking has been linked to increased risk taking and is therefore crucial in influencing behavioral outcomes of risk-taking behavior. Using functional magnetic resonance imaging (fMRI), the neural underpinnings of risk appraisal were studied in a large subject sample (n=188), stratified according to thrill and adventure seeking (TAS) ratings. As defined by a median split of the sample, low and high TAS groups were compared on a simple decision-making task completed during fMRI. The task was designed such that risk (i.e., magnitude of outcome) and gains (i.e., direction of outcome) could be mapped independently. Behavioral analysis indicated that high TAS individuals are more sensitive to rewards but less discriminating between risk with and without punishment and that low TAS individuals are less sensitive to rewards but quite sensitive to receiving punishments in risky situations. Imaging results on the group differences for the interaction between level of risk and level of gain showed differences in the right superior frontal gyrus (BA6), left insula (BA21), right nucleus accumbens, left lentiform nucleus, and left precuneus (BA7). The presented data suggest a neural model of risk processing in sensation seeking individuals such that the positive response to reward outweighs the impact of equivalent loss. This imbalance in approach/avoidance is evident in differences in the underlying neural substrates in TAS individuals and leads to greater risk behavior in the face of potential loss. PMID- 21982932 TI - Grey matter alterations associated with cannabis use: results of a VBM study in heavy cannabis users and healthy controls. AB - Cannabis abuse is related to impairments in a broad range of cognitive functions. However, studies on cannabis abuse in relation to brain structure are sparse and results are inconsistent, probably due to differences in imaging methodology, severity of cannabis abuse, and use of other substances. The goal of the current MRI study was to investigate brain morphology related to current and lifetime severity of cannabis use and dependence in heavy cannabis users without intensive use of other illicit drugs. Voxel-based morphometry was used to assess differences in regional grey and white matter volume between 33 heavy cannabis users and 42 matched controls. Within heavy cannabis users, grey and white matter volume was correlated with measures of cannabis use and dependence. Analyses were focused a priori on the orbitofrontal cortex, anterior cingulate cortex, striatum, amygdala, hippocampus, and cerebellum, regions implicated in substance dependence and/or with high cannabinoid receptor-1 concentrations. Regional grey matter volume in the anterior cerebellum was larger in heavy cannabis users. Within the group of heavy cannabis users, grey matter volume in the amygdala and hippocampus correlated negatively with the amount of cannabis use or dependence. No associations were found between white matter volume and measures of cannabis use or dependence. These findings indicate that associations between heavy cannabis use and altered brain structure are complex. Differential patterns of structural changes for various cannabis use levels imply that alterations in brain structure are associated with specific characteristics of cannabis use and dependence. PMID- 21982931 TI - Repetition of letter strings leads to activation of and connectivity with word related regions. AB - Individuals learn to read by gradually recognizing repeated letter combinations. However, it is unclear how or when neural mechanisms associated with repetition of basic stimuli (i.e., strings of letters) shift to involvement of higher-order language networks. The present study investigated this question by repeatedly presenting unfamiliar letter strings in a one-back matching task during an hour long period. Activation patterns indicated that only brain areas associated with visual processing were activated during the early period, but additional regions that are usually associated with semantic and phonological processing in inferior frontal gyrus were recruited after stimuli became more familiar. Changes in activation were also observed in bilateral superior temporal cortex, also suggestive of a shift toward a more language-based processing strategy. Connectivity analyses reveal two distinct networks that correspond to phonological and visual processing, which may reflect the indirect and direct routes of reading. The phonological route maintained a similar degree of connectivity throughout the experiment, whereas visual areas increased connectivity with language areas as stimuli became more familiar, suggesting early recruitment of the direct route. This study provides insight about plasticity of the brain as individuals become familiar with unfamiliar combinations of letters (i.e., words in a new language, new acronyms) and has implications for engaging these linguistic networks during development of language remediation therapies. PMID- 21982933 TI - Quantifying additive evoked contributions to the event-related potential. AB - Event-related potentials (ERPs) are widely used in basic neuroscience and in clinical diagnostic procedures. In contrast, neurophysiological insights from ERPs have been limited, as several different mechanisms lead to ERPs. Apart from stereotypically repeated responses (additive evoked responses), these mechanisms are asymmetric amplitude modulations and phase-resetting of ongoing oscillatory activity. Therefore, a method is needed that differentiates between these mechanisms and moreover quantifies the stability of a response. We propose a constrained subspace independent component analysis that exploits the multivariate information present in the all-to-all relationship of recordings over trials. Our method identifies additive evoked activity and quantifies its stability over trials. We evaluate identification performance for biologically plausible simulation data and two neurophysiological test cases: Local field potential (LFP) recordings from a visuo-motor-integration task in the awake behaving macaque and magnetoencephalography (MEG) recordings of steady-state visual evoked fields (SSVEFs). In the LFPs we find additive evoked response contributions in visual areas V2/4 but not in primary motor cortex A4, although visually triggered ERPs were also observed in area A4. MEG-SSVEFs were mainly created by additive evoked response contributions. Our results demonstrate that the identification of additive evoked response contributions is possible both in invasive and in non-invasive electrophysiological recordings. PMID- 21982935 TI - Multibiomarker approach at different organization levels in the estuarine Perinereis gualpensis (Polychaeta; Nereididae) under chronic and acute pollution conditions. AB - This work aimed to study biochemical biomarkers and population responses in the polychaete Perinereis gualpensis (Nereididae) from two Chilean estuaries, Lenga (36 degrees 45'S; 73 degrees 10'W) and Tubul-Raqui (37 degrees 14'S,73 degrees 26'W). Lenga estuary is characterized by high mercury and PAH levels as consequence of several historic incidental spills while Tubul is mainly impacted by intensive fish activity. Raqui estuary, with low anthropogenic impact was considered the reference site. Worms were collected in winter and summer periods and tissues were differentiated between anterior (first 40 segments) and posterior region (the rest of the body). Levels of the antioxidant glutathione (GSH), glutathione-S-transferase (GST) activity, total antioxidant capacity against peroxyl radicals (ACAP), lipid peroxidation (TBARS) levels, Na+, K+ ATPase activity (NKA) and metalothioneins (MTs) content were determined in each region. L3 (combined length of prostomiun+peristomiun+first segment) length, size, frequency, histograms and density of individuals were studied in all sites and seasons. Significant differences (p<0.05) were observed among sites for most of the biochemical responses (GSH, GCL, GST, ACAP and TBARS), showing variation between seasons and body regions. Population responses in the most polluted estuary (Lenga) showed differences in size, frequency, lengths and low densities compared with lower impacted sites, indicating the costs associated with tolerance in organisms chronically exposed to estuarine pollution. PMID- 21982934 TI - A bilateral frontoparietal network underlies visuospatial analogical reasoning. AB - Our ability to reason by analogy facilitates problem solving and allows us to communicate ideas efficiently. In this study, we examined the neural correlates of analogical reasoning and, more specifically, the contribution of rostrolateral prefrontal cortex (RLPFC) to reasoning. This area of the brain has been hypothesized to integrate relational information, as in analogy, or the outcomes of subgoals, as in multi-tasking and complex problem solving. Using fMRI, we compared visuospatial analogical reasoning to a control task that was as complex and difficult as the analogies and required the coordination of subgoals but not the integration of relations. We found that analogical reasoning more strongly activated bilateral RLPFC, suggesting that anterior prefrontal cortex is preferentially recruited by the integration of relational knowledge. Consistent with the need for inhibition during analogy, bilateral, and particularly right, inferior frontal gyri were also more active during analogy. Finally, greater activity in bilateral inferior parietal cortex during the analogy task is consistent with recent evidence for the neural basis of spatial relation knowledge. Together, these findings indicate that a network of frontoparietal areas underlies analogical reasoning; we also suggest that hemispheric differences may emerge depending on the visuospatial or verbal/semantic nature of the analogies. PMID- 21982936 TI - Kinetics of ultrasound-assisted lipase-catalyzed glycerolysis of olive oil in solvent-free system. AB - This work reports experimental kinetic data of solvent-free glycerolysis of olive oil using a commercial immobilized lipase (Novozym 435) under the influence of ultrasound irradiation. The experiments were performed in a mechanically stirred reactor under ultrasound irradiation, evaluating the effects of temperature (50 70 degrees C), enzyme concentration (2.5-10 wt%) and glycerol to oil molar ratio (0.8:1-3:1). Results show that ultrasound-assisted lipase-catalyzed glycerolysis might be a potential alternative route to conventional methods, as high contents of reaction products, especially monoglycerides, were achieved at mild irradiation power supply (~130 W) and temperature, in a relatively short reaction time (2h) and low enzyme content (7.5 wt%). To completeness, two simplified kinetic modeling approaches, based on the ordered-sequential bi bi mechanism and reaction stoichiometry, were employed to represent the experimental data, thus allowing a better understanding of the reaction kinetics. PMID- 21982937 TI - Synthesis of CdSe and CdSe/TiO2 nanoparticles under multibubble sonoluminescence condition. AB - CdSe and CdSe/TiO(2) nanoparticles were synthesized under multibubble sonoluminescence (MBSL) condition. The influences of TiO(2) introduced as the sensitizer on the morphology and crystal transformation were investigated. The morphology, phase and optical properties of the final products have been characterized by X-ray powder diffraction, transmission electron microscope, UV vis absorption spectroscopy and photoluminescence spectroscopy. The results showed that as-prepared nanoparticles are well-crystallized, and the suppression of crystal pattern transition as well as the control of CdSe crystal growth can be implemented by coupling of TiO(2) semiconductor. Furthermore, the possible growth mechanism for different morphologies and crystal phases of the nanocrystals were also discussed. PMID- 21982938 TI - Seroepidemiology of herpes simplex virus type 1 and 2 in pregnant women in Switzerland: an obstetric clinic based study. AB - OBJECTIVE: To assess the seroprevalence of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) IgG antibodies and the seroincidence of HSV-1 and HSV-2 infections in pregnant women attending the maternity clinic of the University Hospital Lausanne. STUDY DESIGN: Blood samples from 1030 women were taken at the usual pregnancy visit in the first trimester to assess the prevalence rate of IgG antibodies against HSV-1 and HSV-2 using a type-specific assay. A second blood sample was taken 6-8 weeks postpartum from returning women who were seronegative for HSV-2 or HSV-1 to assess the incidence of seroconversion (primary infection). RESULTS: The seroprevalence rates were 79.4% (95% CI: 76.9-81.9) for HSV-1 and 21.2% (18.7-23.7) for HSV-2 in women 14-46 years old. Type-specific serostatus patterns were as follows: 17.3% HSV-1/-2: +/+, 62.1% HSV-1/-2: +/-, 3.9% HSV-1/ 2: -/+, 16.7% HSV-1/-2: -/-. Two hundred and sixty five women (59 of the 212 seronegative for HSV-1 (27.8%) and 265 of the 812 seronegative for HSV-2 (32.6%)) returned to the outpatient clinic for the post-delivery check and a second blood sample was obtained. One HSV-1 seroconversion was detected (HSV-1 seroconversion rate 2.4%/100 patient * year (95% CI: 0.06-13.4)) in a patient who had symptoms compatible with primary genital herpes. No HSV-2 seroconversion was detected (HSV 2 seroconversion rate: 0/100 patient * year (97.5% one-sided CI: 0-2)). CONCLUSION: Compared to a previous population-based study, our study results suggest a rise in the prevalence of HSV-2 among pregnant women in Switzerland. The low incidence of seroconversion detected during pregnancy is consistent with the very low reported incidence of neonatal herpes in Switzerland. CONDENSATION: This study in a public hospital in Western Switzerland suggests an increasing prevalence of HSV-2, but a low incidence of primary infections in women of childbearing age. PMID- 21982939 TI - Algorithm to diagnose etiology of hypoglycemia after Roux-en-Y gastric bypass for morbid obesity: case series and review of the literature. AB - BACKGROUND: Gastric bypass is a proven treatment option for weight loss and the reduction of medical co-morbid conditions in the obese population. Severe refractory and/or recurrent hypoglycemia can occur, especially in postoperative patients who do not comply with the guidelines for oral glucose consumption. In a very small number of patients, the cause is not dietary indiscretions but, instead, factitious insulin administration or nesidioblastosis. The optimal evaluation and management for these diagnoses is not completely lucid yet important for bariatric surgeons and physicians alike to be familiar. Our objectives were to review the appropriate evaluation and treatment options for etiologies of hypoglycemia after gastric bypass and to create an algorithm that biochemically assesses the etiology of hypoglycemia. The setting was a university hospital in the United States. METHODS: We present the cases of 3 patients who developed symptomatic hypoglycemia from distinct etiologies after laparoscopic Roux-en-Y gastric bypass. We also reviewed the current data regarding diagnosis and treatment. RESULTS: Each patient's evaluation and management is elaborated in detail. We propose a novel algorithm for the biochemical evaluation of hypoglycemia after gastric bypass according to our experience and the review of the literature. CONCLUSION: Most cases of symptomatic hypoglycemia that develop in gastric bypass patients are associated with dietary indiscretions. However, a small subset of patients can develop refractory, recurrent, hyperinsulinemic hypoglycemia from factitious insulin administration or nesidioblastosis. PMID- 21982940 TI - Comment on: fundoplication combined to a medio-gastric plication. PMID- 21982941 TI - Preoperative hemoglobin A1c and postoperative glucose control in outcomes after gastric bypass for obesity. AB - BACKGROUND: Hemoglobin A1c (HbA1c) is a reliable marker for long-term glycemic control in obese diabetic patients. Roux-en-Y gastric bypass improves HbA1c levels over time. However, it is not clear whether the preoperative HbA1c level is a predictor of the outcome in these patients. Our objectives were to understand the predictive capacity of the preoperative HbA1c level in gastric bypass patients at a single university-based Bariatric Center of Excellence. METHODS: We performed a retrospective review of 468 charts from 2006 to 2009 of patients who had undergone Roux-en-Y gastric bypass. Using their preoperative HbA1c status, the patients were categorized and the postoperative outcomes compared. RESULTS: Of the 468 patients reviewed, 310 (66.2%) had a HbA1c of <6.5% (group 1), 92 (19.4%) had a HbA1c of 6.5-7.9% (group 2), and 66 (14.1%) had a HbA1c level of >8.0% (group 3). No difference was found among the 3 groups in baseline body mass index, race, procedure type, length of stay, hospital cost, and smoking status. Groups 2 and 3 were associated with older age, male gender, and higher baseline creatinine. Groups 2 and 3 also had a proportionally greater inpatient postoperative blood glucose level. An elevated postoperative glucose level was independently associated with wound infection (P = .008) and acute renal failure (P = .04). Also, group 3 experienced worse outcomes, including less weight loss at 18 months and fewer diabetic remissions. Over time, however, the vast majority in all groups achieved excellent chronic glycemic control, with HbA1c <6.5% after Roux-en-Y gastric bypass. CONCLUSION: Poor preoperative glycemic control is associated with worse glucose level control postoperatively, fewer diabetic remissions, and less weight loss. An elevated mean postoperative glucose level is independently associated with increased morbidity. PMID- 21982942 TI - Laparoscopic revision of common channel length for chronic diarrhea and malnutrition complicating distal gastric bypass. PMID- 21982943 TI - Comment on: Does laparoscopic gastric banding create hiatal hernias? PMID- 21982944 TI - Developmental and behavioral effects of medetomidine following in ovo injection in chicks. AB - Developmental and behavioral effects of medetomidine were assessed in chicks following in ovo exposure on incubation day 4. Medetomidine at 25 and 50 MUg/egg injected once into the air cell on incubation day 4, dose-dependently decreased the number of viable chick embryos starting on day 10 of the incubation. The percentages of successful hatching in the control and medetomidine treated groups were 93, 60 and 47%, respectively. Embryo lethalities in these groups were 7, 40 and 53%, respectively. In ovo exposure of the chicks to medetomidine at 25 and 50 MUg/egg did not significantly affect the body weight of the chicks as well as their morphometric measurements. In another experiment, 3- and 8-day old chicks exposed to medetomidine in ovo (25 MUg/egg) were monitored in the open-field for 5 min. Medetomidine suppressed the open-field activity of both 3- and 8-day old chicks. This was manifested by a significant increase in the latency to move from the central square of the open-field arena and a decrease in the number of lines crossed (ambulation) with an additional decrease in vocalizations of the 3-day old chicks when compared with respective age-matched control values. In the same medetomidine-exposed chicks the duration of tonic immobility significantly increased in comparison with respective control values. Pharmacological challenge of the medetomidine-exposed chicks (8-day old) with medetomidine at 25 MUg/kg, intramuscularly significantly increased the latencies to onset of sedation and loss of righting reflex and decreased the duration of sleep when compared with the saline-control group challenged in the same manner. The data suggest that medetomidine could be a behavioral teratogen in chicks following in ovo exposure. PMID- 21982945 TI - Mechanism of JmjC-containing protein Hairless in the regulation of vitamin D receptor function. AB - The JmjC-domain-containing protein Hairless (HR) and the vitamin D receptor (VDR) play a critical role in the maintenance of hair growth. Mutations in HR or VDR cause alopecia in humans and mice. Here we show that HR interacts with VDR and induces VDR relocalization in the nuclei. HR associates and colocalizes with nuclear receptor co-repressor (N-CoR) which is localized to subnuclear structures termed matrix-associated deacetylase (MAD) bodies. It is found that the HR mutants (C622G, N970S, D1012N, V1136D), associated with alopecia universalis congenita (AUC) or atrichia with papular lesions (APL), exhibit an abnormal subcellular distribution in addition to the impaired co-repressor activity with VDR. Studies on deletion mutants of HR indicate that the JmjC domain contributes to the co-repressor activity of HR. Our work provides new clues and evidence for the understanding on the role of HR in hair growth. PMID- 21982946 TI - Exploring the neural basis of cognitive reserve in aging. AB - The concept of reserve arose from the mismatch between the extent of brain changes or pathology and the clinical manifestations of these brain changes. The cognitive reserve hypothesis posits that individual differences in the flexibility and adaptability of brain networks underlying cognitive function may allow some people to cope better with brain changes than others. Although there is ample epidemiologic evidence for cognitive reserve, the neural substrate of reserve is still a topic of ongoing research. Here we review some representative studies from our group that exemplify possibilities for the neural substrate of reserve including neural reserve, neural compensation, and generalized cognitive reserve networks. We also present a schematic overview of our ongoing research in this area. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease. PMID- 21982947 TI - Synemin isoforms differentially organize cell junctions and desmin filaments in neonatal cardiomyocytes. AB - Intermediate filaments (IFs) in cardiomyocytes consist primarily of desmin, surround myofibrils at Z disks, and transmit forces from the contracting myofilaments to the cell surface through costameres at the sarcolemma and desmosomes at intercalated disks. Synemin is a type IV IF protein that forms filaments with desmin and also binds alpha-actinin and vinculin. Here we examine the roles and expression of the alpha and beta forms of synemin in developing rat cardiomyocytes. Quantitative PCR showed low levels of expression for both synemin mRNAs, which peaked at postnatal day 7. Synemin was concentrated at sites of cell cell adhesion and at Z disks in neonatal cardiomyocytes. Overexpression of the individual isoforms showed that alpha-synemin preferentially localized to cell cell junctions, whereas beta-synemin was primarily at the level of Z disks. An siRNA targeted to both synemin isoforms reduced protein expression in cardiomyocytes by 70% and resulted in a failure of desmin to align with Z disks and disrupted cell-cell junctions, with no effect on sarcomeric organization. Solubility assays showed that beta-synemin was soluble and interacted with sarcomeric alpha-actinin by coimmunoprecipitation, while alpha-synemin and desmin were insoluble. We conclude that beta-synemin mediates the association of desmin IFs with Z disks, whereas alpha-synemin stabilizes junctional complexes between cardiomyocytes. PMID- 21982948 TI - Characterization of protocadherin-1 expression in primary bronchial epithelial cells: association with epithelial cell differentiation. AB - Protocadherin-1 (PCDH1) is a novel susceptibility gene for asthma that is expressed in airway epithelium. We aimed to characterize PCDH1 mRNA transcripts and protein expression in primary bronchial epithelial cells and to determine regulation of PCDH1 during mucociliary differentiation. Total RNA and protein were isolated from human primary bronchial epithelial cells. PCDH1 transcripts were characterized by rapid amplification of cDNA ends in bronchial epithelial cells of 4 subjects. PCDH1 expression was quantified by quantitative RT-PCR and Western blotting in bronchial epithelial cells directly ex vivo and after air liquid interface (ALI) or submerged culture. We identified 5 novel exons on the 5' end and 1 exon on the 3' end of PCDH1. Novel transcripts showed major variation in expression of intracellular conserved motifs. Expression levels of PCDH1 transcripts encoding exon 1-2 were 4-fold higher, and transcripts encoding exon 3-4 were 15-fold higher in freshly isolated bronchial epithelial cells than in submerged cultures. PCDH1 mRNA (3- to 8-fold) and protein levels (2- to 3 fold) were strongly up-regulated during mucociliary differentiation of primary bronchial epithelial cells in ALI cultures. In summary, PCDH1 transcripts display remarkable variability in expression of conserved intracellular signaling domains. Enhanced PCDH1 expression levels strongly correlate with differentiation of bronchial epithelial cells. PMID- 21982950 TI - Identification of CAD as an androgen receptor interactant and an early marker of prostate tumor recurrence. AB - Markers of prostate tumor recurrence after radical prostatectomy are lacking and highly demanded. The androgen receptor (AR) is a nuclear receptor that plays a pivotal role in normal and cancerous prostate tissue. AR interacts with a number of proteins modulating its stability, localization, and activity. To test the hypothesis that an increased expression of AR partners might foster tumor development, we immunopurified AR partners in human tumors xenografted into mice. One of the identified AR partners was the multifunctional enzyme carbamoyl phosphate synthetase II, aspartate transcarbamylase, and dihydroorotase (CAD), which catalyzes the 3 initial steps of pyrimidine biosynthesis. We combined experiments in C4-2, LNCaP, 22RV1, and PC3 human prostate cell lines and analysis of frozen radical prostatectomy samples to study the CAD-AR interaction. We show here that in prostate tumor cells, CAD fosters AR translocation into the nucleus and stimulates its transcriptional activity. Notably, in radical prostatectomy specimens, CAD expression was not correlated with proliferation markers, but a higher CAD mRNA level was associated with local tumor extension (P=0.049) and cancer relapse (P=0.017). These results demonstrate an unsuspected function for a key metabolic enzyme and identify CAD as a potential predictive marker of cancer relapse. PMID- 21982949 TI - Genetic deletion of TNF receptor suppresses excitatory synaptic transmission via reducing AMPA receptor synaptic localization in cortical neurons. AB - The distribution of postsynaptic glutamate receptors has been shown to be regulated by proimmunocytokine tumor necrosis factor alpha (TNF-alpha) signaling. The role of TNF-alpha receptor subtypes in mediating glutamate receptor expression, trafficking, and function still remains unclear. Here, we report that TNF receptor subtypes (TNFR1 and TNFR2) differentially modulate alpha-amino-3 hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) clustering and function in cultured cortical neurons. We find that genetic deletion of TNFR1 decreases surface expression and synaptic localization of the AMPAR GluA1 subunit, reduces the frequency of miniature excitatory postsynaptic current (mEPSC), and reduces AMPA-induced maximal whole-cell current. In addition, these results are not observed in TNFR2-deleted neurons. The decreased AMPAR expression and function in TNFR1-deleted cells are not significantly restored by short (2 h) or long (24 h) term exposure to TNF-alpha. In TNFR2-deleted cells, TNF-alpha promotes AMPAR trafficking to the synapse and increases mEPSC frequency. In the present study, we find no significant change in the GluN1 subunit of NMDAR clusters, location, and mEPSC. This includes applying or withholding the TNF alpha treatment in both TNFR1- and TNFR2-deleted neurons. Our results indicate that TNF receptor subtype 1 but not 2 plays a critical role in modulating AMPAR clustering, suggesting that targeting TNFR1 gene might be a novel approach to preventing neuronal AMPAR-mediated excitotoxicity. PMID- 21982951 TI - Can we capture the intersections? Older Black women, education, and health. AB - BACKGROUND: Race/ethnicity, gender, and socioeconomic status are the three most prominent factors to predict health outcomes. Despite the fact that persistent health inequalities are found between groups, we know little about how the interrelatedness of these social positions influences the health of older adults. PURPOSE: In this study, we apply a feminist intersectional approach to the study of health inequalities, treating social variables as multiplicative rather than additive to capture the mutually constitutive dimensions of race/ethnicity, gender, and education. METHODS: This paper makes use of data from the National Social Life, Health and Aging Project, a nationally representative sample of 3,005 community-dwelling U.S. adults aged 57 to 85 years old, to explore intersections of race, gender, and education. We use a combination of stratified analysis with an interaction term to test multiplicative effects. RESULTS: First, our findings confirm that Black women with less than a high school education have the poorest self-rated health. Second, at the bivariate level, we find highly educated White men are not the converse of lower educated Black women. Third, at the multivariate level, we find being Black and female has an effect on health beyond those already accounted for by race and gender. CONCLUSION: This research demonstrates the explanatory power of an intersectionality approach to deepen understanding of the overlapping, simultaneous production of health inequalities by race, class, and gender. PMID- 21982952 TI - PolarCath cryoplasty enhances smooth muscle cell apoptosis in a rabbit iliac artery model: an experimental in vivo controlled study. AB - PURPOSE: To in vivo investigate the histological response after single and double cryoplasty therapy in a rabbit iliac artery model. MATERIALS AND METHODS: In total, 40 New Zealand White rabbits underwent percutaneous transluminal angioplasty of the iliac artery using either PolarCath balloon or a conventional angioplasty balloon of equal diameter. Arterial injury, inflammatory response and smooth muscle cells (SMC) apoptosis with the TUNEL (Terminal deoxynucleotidyl transferase dUTP Nick End Labeling) immunohistochemical assay were analyzed. Rabbits were divided between single or double balloon inflation and histological results were compared between cryoplasty and control angioplasty both at 30 min and 72 h. RESULTS: Arterial injury and wall inflammation scores were low and similar between cryoplasty and control groups after single and double balloon inflation. Compared to conventional balloon angioplasty, Polarcath cryoplasty demonstrated superior SMC apoptosis after single inflation at 30 min [12.0+/-1.2 cells/(0.025 mm)2 vs 7.0+/-1.5 cells/(0.025 mm)(2), p=0.002], single inflation at 72 h [9.0+/-1.0 cells/(0.025 mm)(2) vs 5.4+/-1.4 cells/(0.025 mm)(2), p=0.001], double inflation at 30 min [11.6+/-1.5 cells/(0.025 mm)(2) vs 6.8+/-1.4 cells/(0.025 mm)(2), p=0.001] and double inflation at 72h [9.2+/-0.8 cells/(0.025 mm)(2) vs 5.0+/-0.7 cells/(0.025 mm)(2), p=0.001]. There were no significant differences in apoptosis between single and double cryoplasty application at 30 min and 72 h. CONCLUSION: Cryoplasty demonstrated superior rates of SMC apoptosis at 30 min and 72 h and was associated to relatively low arterial injury and inflammation scores. An immediate second PolarCath inflation did not achieve superior apoptosis. PMID- 21982953 TI - Cryosurgery and rhTNF-alpha play synergistic effects on a rat cortex C6 glioma model. AB - Glioma, a type of brain tumor originating from glioma cells, varies widely in aggressiveness and causes serious symptoms, but the treatments are limited. Studies have shown that cryosurgery has multiple effects on tumor treatments, and administration of human tumor necrosis factor-alpha (rhTNF-alpha) arguments the anti-tumor effect of cryotherapy in breast and prostate cancers. To test the hypothesis that cryosurgery and rhTNF-alpha play synergistic effects against brain tumors, we established a brain glioma model on rat cortex regions following different treatments: the G1 group was sham-operated; the G2 group was treated with cryosurgery; the G3 group was treated with rhTNF-alpha; and G4 group received combined treatment with cryosurgery and rhTNF-alpha. Tumor sizes were measured by magnetic resonance imaging; DNA fragmentation was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL assay); P21(WAF1/CIP1) and proliferating cell nuclear antigen (PCNA) expression levels were scored using immunohistochemical staining. G2 and G4 rats had significantly longer survival time than did G1 rats. Tumor sizes in each group were significantly decreased as compared with those in G1 rats. PCNA-positive cells were significantly decreased in G2, G3 and G4 rats as compared with G1 rats. In contrast, DNA fragmentation and P21(WAF1/CIP1)-positive cells were significantly increased in each treatment group. Importantly, a combined treatment enhanced the effects of cryosurgery. Combined treatment with cryosurgery and rhTNF-alpha may have a synergistic effect on glioma tumor therapy, enhancing the inhibition of proliferation and the induction of apoptosis. PMID- 21982955 TI - Luminescent quantum dots as platforms for probing in vitro and in vivo biological processes. AB - In this report we review some of the recent progress made for enhancing the biocompatibility of luminescent quantum dots (QDs) and for developing targeted bio-inspired applications centered on live cell imaging and sensing. We start with a detailed analysis of the surface functionalization strategies developed thus far, and discuss their effectiveness for providing long term stability of the quantum dots in biological media, to changes in pH and to added electrolytes. We then discuss the available conjugation techniques to couple QDs to a variety of biological receptors and compare their effectiveness. In particular, we highlight the implementation of new strategies such as the use of copper-free cyclo-addition reaction (CLICK) chemistry and chemo-selective ligation. We then discuss the advances made for intracellular delivery where ideas such as receptor driven endocytosis and uptake promoted by cell penetrating peptides are used. We then describe a few representative examples where QDs have been used to investigate specific cell biology processes. Such processes include binding of QDs conjugated to the nerve growth factor to membrane specific receptors and intracellular uptake, tracking of membrane protein at the single molecule level, and recognition of ligand bound QDs by T cell receptors. We conclude by discussing issues of toxicity associated with the use of QDs in biology. PMID- 21982956 TI - A double-blind randomized controlled comparison of APDDR-0901, a novel cosmeceutical formulation, and 0.1% adapalene gel in the treatment of mild-to moderate acne vulgaris. AB - Topical retinoids have been widely used in the treatment of acne. They comprise several products used as prescription drugs as well as cosmeceuticals. Of these products, retinol has better tolerability compared with prescription retinoids such as tretinoin, but it is only used in cosmeceuticals due to its low biologic activity. A combination formulation could be an effective alternative to address the problem of decreased therapeutic activity. Recently, hexamidine diisethionate is known to have antibacterial activity, and rose extract has been shown to possess anti-inflammatory activity. In this study, we compared the efficacy and safety of the combination product APDDR-0901 (0.03% retinol, 0.7% rose extract, and 0.05% hexamidine diisethionate) vs 0.1% adapalene gel for the treatment of mild-to-moderate acne. This 12-week, multicenter, double-blinded study included 97 patients with mild-to-moderate acne. Efficacy was evaluated using 4 discrete variables: lesion count, acne grade, physician-assessed global improvement, and patient self-assessment. We also assessed safety profiles, including cutaneous irritation. Both APDDR-0901 and adapalene showed significant improvements without significant differences. Otherwise, the APDDR-0901 group showed better safety profiles, particularly in the first 2 weeks. In conclusion, APDDR-0901 could be an effective and safe alternative in the treatment of mild-to-moderate acne. PMID- 21982954 TI - Structural remodeling of astrocytes in the injured CNS. AB - Astrocytes respond to all forms of CNS insult and disease by becoming reactive, a nonspecific but highly characteristic response that involves various morphological and molecular changes. Probably the most recognized aspect of reactive astrocytes is the formation of a glial scar that impedes axon regeneration. Although the reactive phenotype was first suggested more than 100 years ago based on morphological changes, the remodeling process is not well understood. We know little about the actual structure of a reactive astrocyte, how an astrocyte remodels during the progression of an insult, and how populations of these cells reorganize to form the glial scar. New methods of labeling astrocytes, along with transgenic mice, allow the complete morphology of reactive astrocytes to be visualized. Recent studies show that reactivity can induce a remarkable change in the shape of a single astrocyte, that not all astrocytes react in the same way, and that there is plasticity in the reactive response. PMID- 21982957 TI - Vitrectomy and internal limiting membrane peeling with and without gas tamponade for myopic foveoschisis. AB - PURPOSE: To compare clinical outcomes after vitrectomy and internal limiting membrane (ILM) peeling, with and without gas tamponade, for the treatment of myopic foveoschisis. DESIGN: Retrospective, comparative, interventional case series. METHODS: In this retrospective clinical study, 17 eyes of 17 consecutive patients underwent vitrectomy and ILM peeling for treatment of myopic foveoschisis. Eyes were divided into 2 groups, those with gas tamponade (n = 9) and those without (n = 8). Gas tamponade was chosen according to the period and surgeon's discretion. The changes of foveal anatomy on preoperative optical coherence tomography (OCT) were not considered in the decision. Main outcome measures were the rate of resolution of myopic foveoschisis measured by OCT, the time interval until resolution of myopic foveoschisis, central foveal thickness, and best-corrected visual acuity (BCVA). RESULTS: After surgery, OCT showed a resolution of myopic foveoschisis in 8 eyes (88.9%) in the gas-treated group and in 6 eyes (75.0%) in the no-gas group. This difference between the groups was statistically insignificant (P = .576). The mean period until the resolution of myopic foveoschisis was 2.25 months in the gas-treated group and 4.50 months in the no-gas group (P = .011). The mean BCVA improved significantly in both the gas treated and no-gas groups (P = .011 and P = .017, respectively). CONCLUSIONS: Vitrectomy and ILM peeling without gas tamponade appears to be as effective in the treatment of myopic foveoschisis as vitrectomy with gas tamponade. However, eyes treated with gas tamponade showed more rapid resolution of myopic foveoschisis. PMID- 21982958 TI - Near-infrared autofluorescence in patients with idiopathic submacular choroidal neovascularization. AB - PURPOSE: To investigate near-infrared autofluorescence (IR-AF) patterns and related changes in patients with idiopathic choroidal neovascularization (CNV) treated with intravitreal bevacizumab (IVB). DESIGN: Retrospective observational consecutive case series. METHODS: Bevacizumab was intravitreally injected into 12 eyes of 12 patients with idiopathic CNV as the primary treatment. Color fundus photographs, optical coherence tomography (OCT), fluorescein angiography and indocyanine green angiography (ICGA), and autofluorescence imaging short wavelength and near-infrared autofluorescence (SW-AF and IR-AF) were performed at baseline. Changes in the autofluorescence patterns were evaluated after IVB. RESULTS: All 12 eyes had classic CNV on fluorescein angiography at baseline. OCT showed CNV above the retinal pigment epithelium (RPE) in all eyes. After treatment, the final best-corrected visual acuity improved significantly (P < .001) compared with baseline. IR-AF showed ring-shaped hyperautofluorescence surrounding the CNV corresponding to the dark rim on ICGA in 6 of the 12 eyes on IR-AF at baseline. During the follow-up period after IVB, all 12 eyes had ring shaped hyperautofluorescence. The intensity of the ring-shaped autofluorescence and its contrast increased as the CNV regressed. The contrast of the ring-shaped autofluorescence partially decreased in all 3 eyes with a recurrence. CONCLUSIONS: Ring-shaped hyperautofluorescence on IR-AF in the eyes with idiopathic CNV may indicate an involutional process of CNV enveloped by the RPE because its area corresponded to the dark rim on ICGA that reflects regression of idiopathic CNV. IR-AF can be a useful noninvasive adjunctive examination to evaluate the involution of CNV. PMID- 21982959 TI - Inferior vena cava thrombosis and its relationship with the JAK2V617F mutation and chronic myeloproliferative disease. AB - BACKGROUND: Splanchnic vein thrombosis (SVT) is a typical manifestation of polycythaemia vera (PV) or essential thrombocythaemia (ET). The recently discovered JAK2V617F somatic mutation is closely associated with chronic myeloproliferative disease (CMD). We investigated whether thrombosis involving the inferior vena cava (IVC) is also related to the JAK2V617F mutation or CMD. METHODS: Blood samples were obtained from 40 IVC thrombosis patients. Fifty-three patients with isolated lower extremity deep vein thrombosis (LE-DVT) and 20 SVT patients served as controls. The presence of the JAK2V617F mutation was assessed by real-time polymerase chain reaction (RT-PCR). RESULTS: The JAK2V617F allele was not detected in any of the IVC thrombosis patients but was detected in one patient (2%) with isolated LE-DVT. However, the mutation-carrying patient did not exhibit symptoms of CMD. Even after an observation period of 30months, the patient's complete blood cell count did not exhibit any pathology. In contrast, the JAK2V617F allele was detected in four patients with SVT (20%) and CMD. CONCLUSION: According to our data, there is no evidence that IVC thrombosis is associated with the JAK2V617F mutation or the presence of chronic myeloproliferative disease. PMID- 21982960 TI - Aging and factors related to running economy. AB - The purpose of this study was to investigate the relationship that age has on factors affecting running economy (RE) in competitive distance runners. Fifty-one male and female subelite distance runners (Young [Y]: 18-39 years [n = 18]; Master [M]: 40-59 years [n = 22]; and Older [O]: 60-older [n = 11]) were measured for RE, step rate, lactate threshold (LT), VO2max, muscle strength and endurance, flexibility, power, and body composition. An RE test was conducted at 4 different velocities (161, 188, 215, and 241 m.min(-1)), with subjects running for 5 minutes at each velocity. The steady-state VO2max during the last minute of each stage was recorded and plotted vs. speed, and a regression equation was formulated. A 1 * 3 analysis of variance revealed no differences in the slopes of the RE regression lines among age groups (y = 0.1827x - 0.2974; R2 = 0.9511 [Y]; y = 0.1988x - 1.0416; R2 = 0.9697 [M]; y = 0.1727x + 3.0252; R2 = 0.9618 [O]). The VO2max was significantly lower in the O group compared to in the Y and M groups (Y = 64.1 +/- 3.2; M = 56.8 +/- 2.7; O = 44.4 +/- 1.7 mlO2.kg(-1).min( 1)). The maximal heart rate and velocity @ LT were significantly different among all age groups (Y = 197 +/- 4; M = 183 +/- 2; O = 170 +/- 6 b.min(-1) and Y = 289.7 +/- 27.0; M = 251.5 +/- 32.9; O = 212.3 +/- 24.6 m.min(-1), respectively). The VO2max @ LT was significantly lower in the O group compared to in the Y and M groups (Y = 50.3 +/- 2.0; M = 48.8 +/- 2.9; O = 34.9 +/- 3.2 mlO2.kg(-1).min( 1)). The O group was significantly lower than in the Y and M groups in flexibility, power, and upper body strength. Multiple regression analyses showed that strength and power were significantly related to running velocity. The results from this cross-sectional analysis suggest that age-related declines in running performance are associated with declines in maximal and submaximal cardiorespiratory variables and declines in strength and power, not because of declines in running economy. PMID- 21982961 TI - Computer simulation of the matrix-inclusion interphase in bulk metallic glass based nanocomposites. AB - Atomistic models for matrix-inclusion systems are generated. Analyses of the systems show that interphase layers of finite thickness appear interlinking the surface of the nanocrystalline inclusion and the embedding amorphous matrix. In a first approximation, the interphase is characterized as an amorphous structure with a density slightly reduced compared to that of the matrix. This result holds for both monatomic hard sphere systems and a Cu(47.5)Zr(47.5)Al(5) alloy simulated by molecular dynamics (MD). The elastic shear and bulk modulus of the interphase are calculated by simulated deformation of the MD systems. Both moduli diminish with decreasing density but the shear modulus is more sensitive against density reduction by one order of magnitude. This result explains recent observations of shear band initiation at the amorphous-crystalline interface during plastic deformation. PMID- 21982962 TI - Screw locking elements: a means to modify the flexibility of osteoporotic fracture fixation with DCPs without compromising system strength or stability. AB - This paper analyses whether it is possible to use dynamic compression plates (DCPs) and screw locking elements (SLEs) to vary the flexibility of osteoporotic fracture fixation without compromising the strength and stability of the construct. Compression, torsion and four-point bending static strength tests were conducted. Cyclic load tests of up to 10,000 load cycles were also carried out to determine stiffness performance. Four fixation systems were mounted onto polyurethane bone models. Group 1 consists of the DCP and six cortical screws. Group 2, idem, but with the addition of two SLEs. Group 3, idem, but with the addition of six SLEs. Group 4 used the locking compression plate (LCP) and locking screws. The results indicated no significant difference (p>0.05) in the strength of groups 2-4. It was also observed that the torsional stiffness of group 3 (0.30 Nm/ degrees ) was higher than that of group 2 (0.23 Nm/ degrees ) and similar to that of group 4 (0.28 Nm/ degrees ). Compression stiffness of group 4 (124 N/mm) was higher than that of group 2 (102 N/mm), but lower than that of group 3 (150 N/mm). No notable differences were observed for structural bending stiffness. It is concluded that by using the DCP with SLEs it is possible to modify the stiffness of the fixation construct for the repair of osteoporotic fractures and, in this way, facilitate the conditions suitable on secondary bone healing. PMID- 21982963 TI - Benefits of computed tomography versus risks of radiation for organic gastrointestinal conditions. PMID- 21982964 TI - Foaming at the mouth: ingestion of 35% hydrogen peroxide solution (with video). PMID- 21982965 TI - Making the most of imperfect high-resolution manometry studies. PMID- 21982966 TI - Virus C cure as a motivation for strong lifestyle change? PMID- 21982967 TI - Honeycomb appearance of the liver in Wilson's disease. PMID- 21982968 TI - Gastrointestinal cancer in celiac disease: "the first days are the hardest days, don't you worry anymore?". PMID- 21982969 TI - Sulfasalazine crystalluria-induced anuric renal failure. PMID- 21982970 TI - Histologic and imaging features of mural nodules in mucinous pancreatic cysts. AB - BACKGROUND & AIMS: Mural nodules predict malignancy within pancreatic cysts, but it is not clear whether endoscopic ultrasound (EUS) and computed tomography (CT) accurately identify nodules. We assessed images and the histology of mural nodules in branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) and mucinous cystic neoplasms (MCNs) and identified criteria to distinguish mural nodules from mucus. METHODS: We reviewed pathology specimens and EUS and CT images from consecutive patients with resected BD-IPMNs or MCNs. A blinded interobserver study of the EUS images was then conducted to identify features that distinguished nodules from mucus. After education about these features, the raters interpreted the EUS images again. RESULTS: On the basis of histologic analysis, 22 of 57 cases had epithelial nodules. Cancer or high-grade dysplasia was found in 23% of cysts with nodules versus 3% without nodules (P = .02). On the basis of reports, EUS detected epithelial nodules with 75% sensitivity and 83% specificity, whereas these values were 24% and 100%, respectively, for CT. Mucus accounted for 65% of intracystic lesions detected by EUS and was often diagnosed by using change in body position and fine-needle aspiration. Interobserver analysis identified 3 features that were detected by EUS (echogenicity, edge, and rim) that distinguished mucus from epithelial nodules. The diagnostic accuracy of the raters improved from a mean of 57% to 79% after education about these features (P = .004); accuracy was 90% when all 3 features of mucus were present. CONCLUSIONS: Malignancy is associated with epithelial nodules in BD-IPMNs and MCNs, but most echogenic lesions detected in cysts by EUS are mucus. Knowledge of features that discriminate mucus from mural nodules improves the diagnostic accuracy of EUS. PMID- 21982971 TI - Characterization of chicken endoglin, a member of the zona pellucida family of proteins, and its tissue expression. AB - Endoglin is a TGF-beta co-receptor expressed in endothelial cells, where it plays a crucial role in angiogenesis, cardiovascular development and vascular remodeling. In humans, mutations in the endoglin gene give rise to Hereditary Hemorrhagic Telangiectasia type 1 (HHT1), an autosomal dominant disorder associated with vascular lesions in skin, mucosa and internal organs. So far, endoglin cDNA has been sequenced in several species from mammals, amphibians and birds. While in mammals the characterization of endoglin protein expression and function is well documented, little is known about the protein homologue in birds. In silico analysis by multiple sequences alignment showed a low homology score of 30-33 between the full length chicken endoglin protein and several mammalian homologues. However, a high homology score (80-85) was observed with the cytoplasmic and transmembrane regions and the overall structure of the zona pellucida (ZP) and orphan domains of the extracellular region appear to be conserved. Transient expression of chicken endoglin allowed the identification of a 180-kDa disulfide linked homodimer similar to the mammalian homologues. To further characterize its tissue expression, the novel specific monoclonal antibody (mAb) 7H5A8 was generated against chicken endoglin transfectant cells. The mAb 7H5A8 specifically recognized chicken endoglin by western blot, immunoprecipitation, immunofluorescence flow cytometry as well as immunofluorescence microscopy assays and displayed a positive staining of the endothelium in veins and arteries from frozen tissue sections of lung and bursa of Fabricius. These results may help to further understand the endoglin expression in vertebrates. PMID- 21982972 TI - Detection change points of triplet periodicity of gene. AB - The triplet periodicity (TP) is a distinguished property of protein coding sequences. There are complex genes with more than one TP type along their sequence. We say that these genes contain a triplet periodicity change point. The aim of the work is to find all genes that contain TP change point and attempt to compare the positions of change point in genes with known biological data. We have developed a mathematical method to identify triplet periodicity changes along a sequence. We have found 311,221 genes with the TP change point in the KEGG/Genes database (version 48). It is about 8% from the total database volume (4013150). We showed that the repetitive sequences are not the only cause of such events. We suppose that the TP change point may indicate a fusion of genes or domains. We performed BLAST analysis to find potential ancestral genes for the parts of genes with TP change point. As a result we found that in 131323 cases sequences with TP change point have proper similarities for one or both parts. The relationship between TP change point and the fusion events in genes is discussed. The program realization of the method is available by request to authors. PMID- 21982975 TI - [Initial descriptive analysis of 200 obese adolescents in an adolescent care unit]. AB - Common obesity is a frequent reason for outpatient visits to adolescent clinics. Its high risk of persistence or progression into adulthood is well known. This article is a study of 200 clinical charts of obese adolescents that visited our clinic. The physical, metabolic, psychological, and social characteristics of these patients when they first started their follow-up are described. Body image disturbance and the everyday psychosocial impact of obesity were the most frequent reasons for the first visit. Two-thirds of the adolescent girls had already had unsuccessful follow-ups by other teams or doctors. The average age was 14.5 years and the average body mass index z-score was above 7.4. They suffered from musculoskeletal or respiratory disorders but had few metabolic complications at that stage. Various personal or family psychological and social characteristics were frequently observed as well as certain types of eating disorders. This data may be useful in establishing different profiles that could be used to adapt obese patient care for adolescents. PMID- 21982973 TI - Recombinant vaccines against the mononegaviruses--what we have learned from animal disease controls. AB - The mononegaviruses include a number of highly contagious and severe disease causing viruses of both animals and humans. For the control of these viral diseases, development of vaccines, either with classical methods or with recombinant DNA virus vectors, has been attempted over the years. Recently reverse genetics of mononegaviruses has been developed and used to generate infectious viruses possessing genomes derived from cloned cDNA in order to study the consequent effects of viral gene manipulations on phenotype. This technology allows us to develop novel candidate vaccines. In particular, a variety of different attenuation strategies to produce a range of attenuated mononegavirus vaccines have been studied. In addition, because of their ideal nature as live vaccines, recombinant mononegaviruses expressing foreign proteins have also been produced with the aim of developing multivalent vaccines against more than one pathogen. These recombinant mononegaviruses are currently under evaluation as new viral vectors for vaccination. Reverse genetics could have great potential for the preparation of vaccines against many mononegaviruses. PMID- 21982976 TI - [Amanita proxima poisoning in a child]. AB - Mushroom intoxication due to Amanita proxima poisoning is characterized by moderate gastrointestinal symptoms, followed by severe acute renal failure and sometimes by hepatic cytolysis. This syndrome was described in the 1990s in the southeast of France; we report here the first pediatric case, requiring dialysis but achieving complete recovery. The mother of this 11-year-old boy, who had eaten the same mushrooms but in smaller quantities, had only biological renal and hepatic involvement. PMID- 21982978 TI - Regulation of proliferation, survival, differentiation, and activation by the Signaling Platform for SHP-1 phosphatase. PMID- 21982977 TI - Comprehensive proteomic analysis of host cell lipid rafts modified by HBV infection. AB - Lipid rafts are cholesterol- and sphingolipid-rich membrane microdomains that have been shown to participate in the entry, assembly and budding of various viruses. However, their involvement in HBV replication remains poorly characterized. In a preliminary study, we observed that HBV release could be markedly impaired by methyl-beta-cyclodextrin mediated depletion of cholesterol in lipid rafts, and that this effect could be reversed by replenishment of exogenous cholesterol, suggesting that lipid rafts play an important role in the HBV life cycle. To further understanding how HBV exploited host cell lipid rafts to benefit replication, comprehensive proteomic approaches were used to profile the proteome changes of host cell lipid rafts in response to HBV infection using 2DE-MS/MS, in combination with SILAC-based quantitative proteomics. Using these approaches, a total of 97 differentially expressed proteins were identified. Bioinformatics analysis suggested that multiple host cell pathways were involved in the HBV infection processes including signal transduction, metabolism, immune response, transport, vesicle trafficking, cell adhesion and cellular ion homeostasis. These data will provide valuable clues for further investigation of HBV pathogenesis. PMID- 21982979 TI - Revisiting nuclear phospholipase C signalling in MDS. PMID- 21982981 TI - An NMR study elucidating the binding of Mg(II) and Mn(II) to spinach plastocyanin. Regulation of the binding of plastocyanin to subunit PsaF of photosystem I. AB - In this work we address the question whether light-induced changes in the Mg(II) content in the chloroplast lumen can modulate the electron donation to photosystem I, in particular the electrostatic interaction between plastocyanin (Pc) and the photosystem 1 subunit PsaF. For this, we have used 2D NMR spectroscopy to study the binding of Mg(II) ions and the isolated luminal domain of PsaF to (15)N-labelled Pc. From the chemical-shift perturbations in the (1)H (15)N HSQC spectra, dissociation constants of (4.9 +/- 1.7) mM and (1.4 +/- 0.2) mM were determined for the Pc-Mg(II) and Pc-PsaF complexes, respectively. In both cases, significant chemical-shift changes were observed for Pc backbone amide groups belonging to the two acidic patches, residues 42-45 and 59-61. In addition, competitive effects were observed upon the addition of Mg(II) ions to the Pc-PsaF complex, further strengthening that Mg(II) and PsaF bind to the same region on Pc. To structurally elucidate the Mg(II) binding site we have utilized Mn(II) as a paramagnetic analogue of Mg(II). The paramagnetic relaxation enhancement induced by Mn(II) results in line broadening in the Pc HSQC spectra which can be used to estimate distances between the bound ion and the affected nuclear spins. The calculations suggest a location of the bound Mn(II) ion close to Glu43 in the lower acidic patch, and most likely in the form of a hexaquo complex embedded within the hydration shell of Pc. The results presented here suggest a specific binding site for Mg(II) that may regulate the binding of Pc to photosystem 1 in vivo. PMID- 21982982 TI - Pure forms of the singlet oxygen sensors TEMP and TEMPD do not inhibit Photosystem II. AB - In a recent article (Hakala-Yatkin and Tyystjarvi BBA 1807 (2011) 243-250) it was reported that the singlet oxygen spin traps 2,2,6,6-tetramethylpiperidine (TEMP) and 2,2,6,6-tetramethyl-4-piperidone (TEMPD) inhibit Photosystem II (PSII), the water oxidizing enzyme. O2 evolution, chlorophyll fluorescence and thermoluminescence were measured and were shown to be greatly affected by these chemicals. This work casts doubts over an earlier body of work in which these chemicals were used as spin traps for monitoring 1O2 production when PSII was inhibited by high light intensities. Here we show that these spin probes hardly affect PSII. We show that the commercial batches of TEMPD and TEMP used by Hakala Yatkin and Tyystjarvi contained impurities and/or derivatives that inhibited PSII and caused the specific effects on fluorescence. Earlier work that used pure spin traps to measure 1O2 during photoinhibition, thus remains valid. However, concern must be expressed towards using these spin traps without proper controls. PMID- 21982980 TI - Enhanced expression of Pctk1, Tcf12 and Ccnd1 in hippocampus of rats: Impact on cognitive function, synaptic plasticity and pathology. AB - We previously identified a set of 50 genes that were differentially transcribed in the hippocampal CA1 region of aged, learning-impaired rats compared to aged, superior learning animals during a Morris water maze paradigm. In the current study, we expressed three of these genes (Pctk1, Tcf12 and Ccnd1), which had shown increased transcription in aged, learning impaired rats, in the hippocampus of young rats using viral gene transfer and tested for learning and memory deficits at age 7-14months. Pctk1 injected animals displayed a modest deficit in acquiring latency in both the Morris water maze and the reverse Morris maze. In the radial arm water maze paradigm, Pctk1, Tcf12 and Ccnd1 expressing animals all showed significant deficits in spatial working memory compared to controls. Rats injected with Ccnd1 and Tcf12, but not Pctk1, also showed a significant deficit in spatial reference memory in the radial arm water maze. Electrophysiological experiments revealed no difference in LTP in Ccnd1 and Pctk1 animals. However, LTD induced by low frequency stimulation was observed in control and Ccnd1 animals, but not in Pctk1 treated animals. In addition, neither Ccnd1 nor Pctk1 expression produced any detectable neuropathology. In contrast Tcf12 expressing animals displayed significant neurodegeneration in both CA1 and dentate gyrus. Several Tcf12 animals also developed tumors that appeared to be glioblastomas, suggesting that aberrant Tcf12 expression in the hippocampus is tumorigenic. Thus, behavioral experiments suggested that overexpression of Pctk1 and Ccnd1 produce a deficit in learning and memory, but electrophysiological experiments do not point to a simple mechanism. In contrast, the learning and memory deficits in Tcf12 animals are likely due to neuropathology associated with Tcf12 gene expression. PMID- 21982983 TI - Effect of charged lidocaine on static and dynamic properties of model bio membranes. AB - The effect of the charged lidocaine on the structure and dynamics of DMPC/DMPG (mass fraction of 95/5) unilamellar vesicles has been investigated. Changes in membrane organization caused by the presence of lidocaine were detected through small angle neutron scattering experiments. Our results suggest that the presence of lidocaine in the vicinity of the headgroups of lipid membranes leads to an increase of the area per lipid molecule and to a decrease of membrane thickness. Such changes in membrane structure may induce disordering of the tail group. This scenario explains the reduction of the main transition temperature of lipid membranes, as the fraction of lidocaine per lipid molecules increases, which was evident from differential scanning calorimetry results. Furthermore neutron spin echo spectroscopy was used for the dynamics measurements and the results reveal that presence of charged lidocaine increases the bending elasticity of the lipid membranes in the fluid phase and slows the temperature-dependent change of bending elasticity across the main transition temperature. PMID- 21982985 TI - Bilateral simultaneous traumatic upper arm compartment syndromes associated with anabolic steroids. AB - BACKGROUND: Acute compartment syndrome, a surgical emergency, is defined as increased pressure in an osseofascial space. The resulting reduction of capillary perfusion to that compartment requires prompt fasciotomy. Treatment delay has a poor prognosis, and is associated with muscle and nerve ischemia, resultant infarction, and late-onset contractures. OBJECTIVES: We report a case of traumatic bilateral upper limb acute compartment syndrome associated with anabolic steroids, requiring bilateral emergency fasciotomies. CASE REPORT: A 25 year-old male bodybuilder taking anabolic steroids, with no past medical history, presented to the Emergency Department 25 min after a road traffic accident. Secondary survey confirmed injuries to both upper limbs with no distal neurovascular deficit. Plain radiographs demonstrated bilateral metaphyseal fractures of the distal humeri. Within 2 h of the accident, the patient developed clinical features that were consistent with bilateral upper arm compartment syndrome. Bilateral fasciotomies of both anterior and posterior compartments were performed, confirming clinical suspicion. CONCLUSION: We suggest consideration of a history of anabolic steroid use when evaluating patients with extremity trauma. PMID- 21982986 TI - Perniosis: a case of painful progressive rash over the distal extremities. PMID- 21982987 TI - Foreign body (pen) in the stomach and lower esophagus. PMID- 21982988 TI - Rapid onset of bilateral lower extremity swelling and pain. PMID- 21982989 TI - Paroxysmal supraventricular tachycardia in an octogenarian. AB - BACKGROUND: Paroxysmal supraventricular tachycardia is a common dysrhythmia that occurs at all ages. Its management is determined by presenting symptoms and previous history of the patient. Patients present with a continuum of symptoms ranging from palpitations to syncope. The incidence of supraventricular tachycardia increases with age. OBJECTIVES: To discuss the etiology, precipitating factors, and acute management of supraventricular tachycardia; and to discuss nodal reentry circuits and representative electrocardiographic findings. CASE REPORT: We present the case of an 84-year-old man with gallstone pancreatitis, choledolcholithiasis, and cholecystitis complicated by paroxysmal supraventricular tachycardia. We review this dysrhythmia, emphasizing its significance in elderly patients. CONCLUSION: Supraventricular tachycardia is a common dysrhythmia that can result in syncope or myocardial infarction. We present a case of an elderly man with new-onset atrioventricular (AV) nodal reentry tachycardia, possibly precipitated by overdrive of his autonomic nervous system due to pain and infection. As the percentage of the elderly in our population is growing rapidly and the incidence of AV nodal reentry tachycardia increases with age, emergency physicians should be familiar with this dysrhythmia its etiology, precipitating factors, presentations, and treatment. It will present more frequently in the future. PMID- 21982990 TI - Feasibility of continuous glucose monitoring in critically ill emergency department patients. AB - BACKGROUND: Glucose control is important in the management of critically ill patients. However, strict glucose control requires a large amount of nursing resources, especially in overcrowded emergency departments (EDs). OBJECTIVES: A continuous glucose monitoring system (CGMS) may be beneficial for glucose control in the ED. The objective of this study was to determine the test characteristics of CGMS in critically ill ED patients. METHODS: A prospective observational study of critically ill ED patients was conducted. During a patient's visit to the ED, a CGMS sensor measured their interstitial fluid glucose levels continuously. Capillary glucose was measured every hour and used for glucose control and as a reference value. CGMS values were recorded in real time and compared with capillary glucose values. RESULTS: A total of 122 pairs of capillary and CGMS glucose values in 12 patients were analyzed. The correlation coefficient was 0.87, and Bland-Altman analysis showed that 117 pairs (95.9%) were within a 95% confidence interval. A Clarke Error Grid Analysis indicated an overall accuracy of 96.8% (Zones A and B). However, the mean absolute relative difference (MARD) was significantly higher in the hypoglycemic range than in a normo- or hyperglycemic range (p = 0.001). The sensitivity and positive predictive value of CGMS for detecting hypoglycemia were 33.3% and 16.7%, respectively. The CGMS specificity and negative predictive value were 95.8% and 98.3%, respectively. There was no linear correlation between MARD and body mass index, axillary temperature, inotrope score, and base deficit (all p-value >0.05). CONCLUSION: CGMS demonstrated good clinical accuracy by Clarke Error Grid Analysis. There also was high agreement between CGMS and capillary glucose levels. However, CGMS demonstrated only limited real-time hypoglycemia detection ability in critically ill ED patients. PMID- 21982991 TI - Automated methods for the location of the boundaries of chromatographic peaks. AB - Several simple techniques are presented for the identification of the boundaries of chromatographic peaks. These methods provide a significant reduction in the time needed to perform the rapid, automatic calculation of the central peak moments and to evaluate the quality of a separation while improving the accuracy of the measurements of column efficiencies. It was found that the identification of the peak boundaries as functions of the peak widths and the examination of the slope of the signal to noise versus time plot are viable alternatives to a manual determination. PMID- 21982992 TI - Kinetic optimisation of open-tubular liquid-chromatography capillaries coated with thick porous layers for increased loadability. AB - The kinetic optimisation of open-tubular liquid chromatography (OTLC) columns has been revisited by taking the thick-film effects for porous coatings on retention, column resistance, band broadening and mass loadability into account. Considering the most advantageous case (i.e. where the retentive layer allows for the same high internal diffusion coefficient as conventional porous particles), calculations show the need for the development of coating procedures leading to porous films filling up approximately 50-70% of the total column diameter. Furthermore, to achieve optimum kinetic performance for separations of small molecules with total analysis times of less than 8h (k'=9), total column diameters should be less than 6 MUm with lengths typically greater than 0.8m for N values of 125,000-500,000 at a pressure of 400 bar. The use of elevated temperature LC (90 degrees C) is also shown to increase the allowable total column diameter to up to 9 MUm for a larger range of N values (100,000-880,000). PMID- 21982993 TI - Preparative separation of 1,3,6-pyrenetrisulfonic acid trisodium salt from the color additive D&C Green No. 8 (pyranine) by pH-zone-refining counter-current chromatography. AB - In developing analytical methods for batch certification of the color additive D&C Green No. 8 (G8), the U.S. Food and Drug Administration needed the trisodium salt of 1,3,6-pyrenetrisulfonic acid (P3S) for use as a reference material. Since P3S was not commercially available, preparative quantities of it were separated from portions of a sample of G8 that contained ~3.5% P3S. The separations were performed by pH-zone-refining counter-current chromatography using dodecylamine (DA) as the hydrophobic counterion. The added DA enabled partitioning of the polysulfonated components into the organic stationary phase of the two-phase solvent system used, 1-butanol-water (1:1). Thus, a typical separation that involved 20.3g of G8, using sulfuric acid as the retainer acid and 20% DA in the stationary phase and 0.1M sodium hydroxide as the mobile phase, resulted in ~0.58 g of P3S of greater than 99% purity. The identification and characterization of the separated P3S were performed by elemental analyses, proton nuclear magnetic resonance, high-resolution mass spectrometry, ultra-violet spectra, and high performance liquid chromatography. PMID- 21982994 TI - Micro liquid-liquid extraction combined with large-volume injection gas chromatography-mass spectrometry for the determination of haloacetaldehydes in treated water. AB - Haloacetaldehydes (HAs) are becoming the most widespread disinfection by-products (DBPs) found in drinking water, besides trihalomethanes and haloacetic acids, generated by the interaction of chemical disinfectants with organic matter naturally present in water. Because of their high potential toxicity, HAs have currently received a singular attention, especially trichloroacetaldehyde (chloral hydrate, CH), the most common and abundant compound found in treated water. The aims of this study are focused on the miniaturisation of EPA Method 551.1, including some innovations such as the use of ethyl acetate as the extracting solvent, the enhancement of HAs stability in aqueous solutions by adjusting the pH ~3.2 and the use of a large-volume sample injection (30 MUL) coupled to programmed temperature vaporizer-gas chromatography-mass spectrometry to improve both sensitivity and selectivity. In optimised experimental conditions, the limits of detection for the 7 HAs studied ranged from 6 to 20 ng/L. Swimming pools have recently been recognized as an important source of exposure to DBPs and as a result, in this research for the first time, HAs have been determined in this type of water. Two HAs have been found in the analysed water: CH at concentrations between 1.2-38 and 53-340 MUg/L and dichloroacetaldehyde between 0.07-4.0 and 1.8-23 MUg/L in tap and swimming pool waters, respectively. PMID- 21982995 TI - Microproteomic analysis of 10,000 laser captured microdissected breast tumor cells using short-range sodium dodecyl sulfate-polyacrylamide gel electrophoresis and porous layer open tubular liquid chromatography tandem mass spectrometry. AB - Precise proteomic profiling of limited levels of disease tissue represents an extremely challenging task. Here, we present an effective and reproducible microproteomic workflow for sample sizes of only 10,000 cells that integrates selective sample procurement via laser capture microdissection (LCM), sample clean-up and protein level fractionation using short-range SDS-PAGE, followed by ultrasensitive LC-MS/MS analysis using a 10 MUm i.d. porous layer open tubular (PLOT) column. With 10,000 LCM captured mouse hepatocytes for method development and performance assessment, only 10% of the in-gel digest, equivalent to ~1000 cells, was needed per LC-MS/MS analysis. The optimized workflow was applied to the differential proteomic analysis of 10,000 LCM collected primary and metastatic breast cancer cells from the same patient. More than 1100 proteins were identified from each injection with >1700 proteins identified from three LCM samples of 10,000 cells from the same patient (1123 with at least two unique peptides). Label free quantitation (spectral counting) was performed to identify differential protein expression between the primary and metastatic cell populations. Informatics analysis of the resulting data indicated that vesicular transport and extracellular remodeling processes were significantly altered between the two cell types. The ability to extract meaningful biological information from limited, but highly informative cell populations demonstrates the significant benefits of the described microproteomic workflow. PMID- 21982996 TI - Surface-initiated molecularly imprinted polymeric column: In situ synthesis and application for semi-preparative separation by high performance liquid chromatography. AB - In this work, we prepared a monolithic and surface initiated molecularly imprinted polymeric (MIP) column for HPLC and explored its application for template separation from plant extract. The silica beads (40-60 MUm) were coupled with initiator on the surface and then packed in to a stainless steel HPLC column. The pre-polymerization mixture (the template, functional monomer and crosslinker were emodin, acrylamide and divinylbenzene, respectively) was injected into the column and polymerized by thermal initiation. The prepared MIP column exhibited excellent retention capability and large imprinted factor for template (the retention time and imprinted factor for emodin on MIP column were 16.26 min and 7.21, respectively). Moreover, the emodin-molecularly imprinted polymeric column could be applied to separate emodin from alcohol extract of Rheum palmatum L. at semi-preparative scale and 1.2 mg of emodin was obtained in 4 h. PMID- 21982997 TI - Clinical outcomes of manual bowel decompression (milking) in the mechanical small bowel obstruction: a prospective randomized clinical trial. AB - BACKGROUND: The aim of this prospective randomized study was to investigate the effects of manual bowel decompression in patients who were operated on for mechanical small bowel obstruction. METHODS: Between March 2008 and February 2010, 40 consecutive patients with mechanical small bowel obstruction were randomized into 2 clinically comparable groups. The intestinal content of the dilated small bowel was caressed to the stomach (by milking) and aspirated via a nasogastric tube in the milking group (group M, n = 20) and left uncaressed in the control Group (group C, n = 20). Patients' characteristics and general operative outcomes were compared and analyzed. RESULTS: The resumption of a regular diet and postoperative hospital stay (P = .68) were not significantly different in groups M and group C. Similarly, there were no differences between the 2 groups regarding respiratory complications (P = .34), bacterial translocation (P = 1), or wound infection (P = 1). CONCLUSIONS: The findings suggest that routine milking is unnecessary in mechanical small bowel obstruction. PMID- 21982998 TI - Subcutaneous delivery of nanoconjugated doxorubicin and cisplatin for locally advanced breast cancer demonstrates improved efficacy and decreased toxicity at lower doses than standard systemic combination therapy in vivo. AB - BACKGROUND: Combination cytotoxic agents in breast cancer carry dose-limiting toxicities. The aim of this study was to test the hypothesis that nanocarrier conjugated doxorubicin and cisplatin would have improved tumor efficacy with decreased systemic toxicity over standard drugs, even at lower doses. METHODS: Female Nu/Nu mice were injected in the breast with human MDA-MB-468LN cells and treated with either standard or nanocarrier-conjugated combination therapy (doxorubicin plus cisplatin) at 50% or 75% maximum tolerated dose (MTD) and monitored for efficacy and toxicity over 12 weeks. RESULTS: Efficacy results for mice treated with hyaluronan-conjugated doxorubicin and cisplatin at 50% MTD were as follows: 5 complete responses, 2 partial responses, and 1 case of stable disease. For hyaluronan-conjugated doxorubicin and cisplatin at 75% MTD, efficacy results were as follows: 7 complete responses, 1 partial response. All complete responses were confirmed histologically. In comparison, mice given standard doxorubicin and cisplatin at 50% MTD demonstrated progressive disease in 6, stable disease in 1, and partial response in 1. For standard doxorubicin and cisplatin at 75% MTD, there were 5 cases of progressive disease and 3 of stable disease (P < .0001 on multivariate analysis of variance). At 75% MTD, standard drug-treated mice had significant weight loss compared to nanocarrier drug treated mice (P < .001). CONCLUSIONS: Subcutaneous nanocarrier delivery of doxorubicin and cisplatin demonstrated significantly improved efficacy with decreased toxicity compared with standard agent combination therapy at all doses tested, achieving complete pathologic tumor response. PMID- 21982999 TI - Resident fatigue in 2010: where is the beef? AB - BACKGROUND: The Accreditation Council for Graduate Medical Education Common Program Requirements for all residency programs (effective July 1, 2011) will limit postgraduate year-1 duty hour length to 16 hours of call. Previous studies have shown some decrement in post-call task performance. We designed a study to evaluate if these decrements still exist in 2010 and to determine specifically when they occur. METHODS: Fourteen residents were tested on 4 simulator tasks during 5 separate call periods. These tasks were completed serially at 4 different time (T) intervals (T0, T12, T18, and T24) over a 24-hour period. Task performance was measured at each of these intervals. The residents completed a post-call survey. RESULTS: Over the 24-hour call there was a trend toward decreased time for the completion of tasks with preservation of accuracy and efficiency. The performance of some residents actually improved and there was minimal correlation between perceived fatigue and performance. CONCLUSIONS: These data show no decrease in junior or senior resident task performance over a 24 hour call period, and do not support the 2011 Accreditation Council for Graduate Medical Education maximum duty hour length of 16 hours. PMID- 21983000 TI - The professionalism curriculum as a cultural change agent in surgical residency education. AB - BACKGROUND: Teaching professionalism effectively to fully engaged residents is a significant challenge. A key question is whether the integration of professionalism into residency education leads to a change in resident culture. METHODS: The goal of this study was to assess whether professionalism has taken root in the surgical resident culture 3 years after implementing our professionalism curriculum. Evidence was derived from 3 studies: (1) annual self assessments of the residents' perceived professionalism abilities to perform 20 defined tasks representing core Accrediting Council on Graduate Medical Education professionalism domains, (2) objective metrics of their demonstrated professionalism skills as rated by standardized patients annually using the objective structure clinical examination tool, and (3) a national survey of the Surgical Professionalism and Interpersonal Communications Education Study Group. RESULTS: Study 1: aggregate perceived professionalism among surgical residents shows a statistically significant positive trend over time (P = .016). Improvements were seen in all 6 domains: accountability, ethics, altruism, excellence, patient sensitivity, and respect. Study 2: the cohort of residents followed up over 3 years showed a marked improvement in their professionalism skills as rated by standardized patients using the objective structure clinical examination tool. Study 3: 41 members of the national Surgical Professionalism and Interpersonal Communications Education Study Group rated their residents' skills in admitting mistakes, delivering bad news, communication, interdisciplinary respect, cultural competence, and handling stress. Twenty-nine of the 41 responses rated their residents as "slightly better" or "much better" compared with 5 years ago (P = .001). Thirty-four of the 41 programs characterized their department's leadership view toward professionalism as "much better" compared with 5 years ago. CONCLUSIONS: All 3 assessment methods suggest that residents feel increasingly prepared to effectively deal with the professionalism challenges they face. Although professionalism seminars may have seemed like an oddity several years ago, residents today recognize their importance and value their professionalism skills. As importantly, department chairpersons report that formal professionalism education for residents is viewed more favorably compared with 5 years ago. PMID- 21983001 TI - Comparison of perioperative outcomes in patients undergoing laparoscopic versus open abdominoperineal resection. AB - BACKGROUND: The aim of this study was to retrospectively compare the outcomes of laparoscopic abdominoperineal resection (APR) and open APR. METHODS: A multicenter, retrospective analysis was performed. The University HealthSystem Consortium database was accessed and searched for International Classification of Diseases, Ninth Revision, codes between October 2008 and January 2010. Discharge data were collected on patients undergoing laparoscopic APR and open APR. RESULTS: Six hundred sixty-seven patients underwent laparoscopic APR, and 2,443 underwent open APR. When lower risk patient groups with minor or moderate severity of illness were compared, laparoscopic APR showed lower morbidity, reduced length of stay, reduced cost, and reduced incidence of intensive care unit admission. Comparative analysis showed no significant difference in mortality rate or 30-day readmission. When higher risk patients were compared, there were significantly reduced costs and reduced incidence of intensive care unit cases in the laparoscopic group. CONCLUSIONS: Patients undergoing laparoscopic APR had overall superior perioperative outcomes compared with those undergoing open APR. Laparoscopic APR demonstrates excellent perioperative outcomes in appropriately selected patients. PMID- 21983002 TI - Three-dimensional fit of CAD/CAM-made zirconia copings. AB - OBJECTIVES: CAD/CAM-technologies aim for a standardized, accurate production of dental restorations out of high strength materials (zirconia). The three dimensional internal fit of CAD/CAM-manufactured zirconia copings was evaluated in vitro to verify the realizability of this aim. METHODS: The analysis was based on ceramic master dies of prepared teeth and corresponding virtual CAD surfaces. Five copings per die were manufactured with two different CAD/CAM-technologies: milling and grinding. The internal fit was determined by a three-dimensional replica technique by optical digitization and computer-assisted analysis. RESULTS: Mean internal gaps were 134/84MUm (SD 78/28) for molar and 93/69MUm (SD 56/35) for premolar copings (milling/grinding) using a digitizable silicone for the replicas representing the cement space; they were statistically significant regarding tooth and CAD/CAM-system (p<0.001). SIGNIFICANCE: All zirconia copings showed an internal accuracy of fit where the gap widths ranged within the current clinical recommendations. However, there still is room for improvement and further standardization of CAD/CAM-technologies. PMID- 21983004 TI - From pharmacovigilance to therapy amelioration in paediatric patients: the role of the clinical pharmacologists and family paediatricians. Part of a series on Paediatric Pharmacology, guest edited by Gianvincenzo Zuccotti, Emilio Clementi, and Massimo Molteni. AB - An active pharmacovigilance approach is advisable in paediatric pharmacotherapy as it contributes to generate knowledge promptly and to enhance the estimation of true risk in clinical practice. Reports and studies from the scientific community and regulatory agencies have shown that effective methods for early detection of adverse drug reaction and pharmacoepidemiological studies are a primary need since they increase drug safety in the paediatric population. In this perspective article we describe how pharmacologists and paediatricians may actively synergise to optimise drug therapies and their management in paediatric patients. PMID- 21983003 TI - Myocardial Tbx20 regulates early atrioventricular canal formation and endocardial epithelial-mesenchymal transition via Bmp2. AB - During early embryogenesis, the formation of the cardiac atrioventricular canal (AVC) facilitates the transition of the heart from a linear tube into a chambered organ. However, the genetic pathways underlying this developmental process are poorly understood. The T-box transcription factor Tbx20 is expressed predominantly in the AVC of early heart tube. It was shown that Tbx20 activates Nmyc1 and suppresses Tbx2 expression to promote proliferation and specification of the atrial and ventricular chambers, yet it is not known if Tbx20 is involved in early AVC development. Here, we report that mice lacking Tbx20 in the AVC myocardium fail to form the AVC constriction, and the endocardial epithelial mesenchymal transition (EMT) is severely perturbed. Tbx20 maintains expression of a variety of genes, including Bmp2, Tbx3 and Hand1 in the AVC myocardium. Intriguingly, we found Bmp2 downstream genes involved in the EMT initiation are also downregulated. In addition, re-expression of Bmp2 in the AVC myocardium substantially rescues the EMT defects resulting from the lack of Tbx20, suggesting Bmp2 is one of the key downstream targets of Tbx20 in AVC development. Our data support a complex signaling network with Tbx20 suppressing Tbx2 in the AVC myocardium but also indirectly promoting Tbx2 expression through Bmp2. The spatiotemporal expression of Tbx2 in the AVC appears to be balanced between these two opposing signals. Overall, our study provides genetic evidence that Tbx20 has essential roles in regulating AVC development that coordinate early cardiac chamber formation. PMID- 21983005 TI - The orchestration of cellular and humoral responses is facilitated by divergent intracellular antigen trafficking in nanoparticle-based therapeutic vaccine. AB - Therapeutic vaccination for the treatment of chronic hepatitis B is promising but has so far shown limited clinical efficacy. Herein, we employ polylactide nanoparticles (NPs) as the vaccine adjuvant and systematically explore their effect on activation of specific immunity and the underlying theoretical mechanisms. In vitro studies show that hepatitis B surface antigen (HBsAg) accumulates in antigen-presenting cells (APCs) to a larger content (270%) with the assistant of NP in comparison with the pure-antigen group. Besides the elevated costimulators (CD80/86) and increased major histocompatibility complex (MHC) II molecules, the MHC I molecules are also found upregulated. This result is mostly owing to the divergent antigen trafficking ways of NP-antigen in APCs, especially for the escape of exogenous HBsAg from the lysosomes to the cytosol. Interestingly, the MHC I level is downregulated in alum-antigen group, indicating a possible reason for its inefficiency in priming cellular response. Further in vivo experiments establish that NP-antigen group indeed enhances the CD8(+) CTL cytotoxicity and IFN-gamma cytokine secretion. Meanwhile, specific antibody titer is also upregulated, and even surpasses that of the commercialized alum-antigen. All these results strongly support that NP-based antigen promotes an orchestration of cellular and humoral immune response, exhibiting favorable intrinsic properties to be applied in therapeutic vaccines. PMID- 21983006 TI - Anticipatory postural adjustments in children with hemiplegia and diplegia. AB - Anticipatory postural adjustments (APAs) play an important role in the performance of many activities requiring the maintenance of standing posture. However, little is known about if and how children with cerebral palsy (CP) generate APAs. Two groups of children with CP (hemiplegia and diplegia) and a group of children with typical motor development performed arm flexion and extension movements while standing on a force platform. Electromyographic activity of six trunk and leg muscles and displacement of center of pressure (COP) were recorded. Children with CP were able to generate anticipatory postural adjustments and produce directionally specific APAs and COP displacements similar to those described in adults and typically developing children. However, children with diplegia were unable to generate APAs of the same magnitude as children with typical development and hemiplegia and had higher baseline muscle activity prior to movement. In children with diplegia, COP was posteriorly displaced and peak acceleration was smaller during bilateral extension compared to children with hemiplegia. The outcomes of the study highlight the role of APAs in the control of posture of children with CP and point out the similarities and differences in anticipatory control in children with diplegia and hemiplegia. These differences may foster ideas for treatment strategies to enhance APAs in children with CP. PMID- 21983007 TI - Effects of etanercept treatment on lipid profile in patients with moderate-to severe chronic plaque psoriasis: a retrospective cohort study. AB - Treatment with tumor necrosis factor alpha (TNF-alpha) inhibitors may have favourable effects on the lipid profile. This is the first study to assess the impact of etanercept on the lipid profile in patients with moderate-to-severe plaque psoriasis. To investigate the effect of etanercept on the lipid profile after 24 weeks of treatment in patients with moderate-to-severe plaque psoriasis. We conducted a retrospective cohort study reviewing the medical records of 45 consecutive patients who were treated for psoriasis with etanercept between June 2006 and September 2009. Demographic and clinical data were collected. Levels of total cholesterol, LDL-C, HDL-C, triglycerides, fasting glucose and C-reactive protein were recorded at the start of etanercept and at week 24. Levels of total cholesterol, LDL-C and triglycerides increased after 24 weeks of treatment with etanercept, with mean differences of 7.1 mg/dL (p=0.505), 2.0 mg/dL (p=0.718) and 2.8 mg/dL (p=0.180), respectively. HDL-C decreased, with a mean difference of 1.4 mg/dL (p=0.995). None of these changes were statistically significant. We found no favourable changes on the lipid profile after 24 weeks of treatment with etanercept in responding patients with chronic plaque psoriasis. PMID- 21983008 TI - Patterns and predictors of sexual activity among women in the Hormone Therapy trials of the Women's Health Initiative. AB - OBJECTIVE: The aim of this study was to determine the patterns and predictors of sexual activity in the Hormone Therapy (HT) Trials of the Women's Health Initiative (WHI). METHODS: Sexual activity questions were administered to 27,347 women ages 50 to 79 years at baseline and at year 1 and to a random 8.6% subsample at years 3 and 6. The associations with demographic and health characteristics were determined. RESULTS: Sexual activity at baseline was 60.7%, 44.9%, and 28.2% in the 50- to 59-, 60- to 69-, and 70- to 79-year-old age groups, respectively. Most of the participants were satisfied with their current sexual activity (63.2%). Of those dissatisfied, 57% preferred more sexual activity. Vaginal atrophy correlated with sexual inactivity at baseline (P < 0.001). The correlates associated with stopping sexual activity at year 1 included poor/fair self-rated health, lack of satisfaction with quality of life, depression, and loss of partner (P < 0.001). The strongest predictor of sexual activity at year 1 was sexual activity at baseline (odds ratio, 96.71; 95% CI, 81.90-114.20). A subset analysis of women adherent with HT or placebo at years 3 and 6 suggested that HT was associated with a higher percentage of participants reporting sexual activity (P = 0.01). CONCLUSIONS: Most women in the WHI HT Trials were satisfied with their sexual activity. Of those who were dissatisfied, the majority preferred more, rather than less, sexual activity. Vaginal atrophy at baseline correlated with sexual inactivity, and sexual activity at baseline was the strongest identified predictor of sexual activity at year 1. HT use was not predictive of ongoing sexual activity in the intent-to-treat analysis. This report further characterizes the participants in the WHI HT trials and reveals the complexity of factors related to the prevalence of sexual activity and satisfaction. PMID- 21983009 TI - Carotid and brachial arterial enlargement in postmenopausal women with hypertension. AB - OBJECTIVE: The aim of this study was to test whether systemic hypertension influences brachial and carotid artery remodeling in postmenopausal women. A secondary aim was to evaluate the possible role of pulse pressure. METHODS: We enrolled 100 postmenopausal women affected by hypertension (cases) and 100 women with blood pressure within the reference range (controls) matched for age and body mass index because the influence of these variables on artery diameter is well known. Clinical and biochemical parameters were also assessed. All women underwent B-mode ultrasonography to measure the carotid and brachial artery diameter. RESULTS: The case group had significantly larger brachial and common carotid artery diameters than control groups (P < 0.001). This result did not change after correction for confounding variables. Indeed, the women with hypertension had higher glucose and insulin levels and greater carotid atherosclerosis prevalence than did the control population. A multivariate linear regression analysis showed a correlation between artery diameters and hypertension status in the whole population. To evaluate the influence of pulse pressure, each group (cases and controls) was divided into two subgroups, according to the group-specific pulse pressure median. The women with a pulse pressure rate higher than the median value had larger artery diameters compared with those with lower pulse pressure rates in both groups with and without hypertension. CONCLUSIONS: Hypertension can promote generalized artery enlargement, and pulse pressure also plays a role in artery remodeling. Interestingly, pulse pressure seems to influence arterial diameter in individuals with blood pressure within the reference range. The role of hypertension in artery remodeling behind age and the body mass index requires further investigations on the mechanisms underlying remodeling. PMID- 21983010 TI - Correlates of human immunodeficiency virus cervicovaginal shedding among postmenopausal and fertile-aged women. AB - OBJECTIVE: The aims of this study were to compare the intensity of human immunodeficiency virus (HIV)-RNA genital shedding among postmenopausal (PM) and fertile-aged (F) women and to investigate the association between viral shedding and gynecological features, HIV plasma viral loads, and other markers of HIV disease progression. METHODS: We interviewed 146 HIV-infected women (73 PM/73 F) in search of gynecological complaints and signs and symptoms of HIV disease and obtained additional information concerning HIV infection by medical chart review. Cervicovaginal lavages (CVLs) were collected for assessment of HIV shedding. Laboratory analyses included CD4 cell counts, HIV-RNA quantitation in plasma and CVL, and screening for concurrent genital infections. RESULTS: HIV-RNA genital shedding was detected in 16.4% of PM and 21.9% of F women (P = 0.400), and the intensity of HIV shedding did not differ between both groups (means-PM: 1.4log/mL; F: 1.4log/mL; P = 0.587). Three women (2 PM/1 F) exhibited viral shedding in the absence of detectable viremia. HIV plasma viral loads correlated with HIV shedding in both groups. In multivariable analysis, HIV plasma viral loads were independently associated with HIV shedding in both groups. Moreover, the intensity of shedding was independently associated with vaginal pH, tumor necrosis factor alpha concentrations in CVL, and HIV plasma viral loads. CONCLUSIONS: Despite significant changes that occur in the vaginal mucosa of PM women, HIV cervicovaginal shedding was not significantly influenced by this state in our cohort. In contrast, increased vaginal pH and genital inflammation, evidenced by increased tumor necrosis factor alpha concentrations in CVL and HIV plasma viral loads, were independently associated with the intensity of HIV shedding in PM and F women. PMID- 21983011 TI - A matter of scholarly clarification (Comment on H. Wipfli, G. Huang, 2011. Power of the process: evaluating the impact of the framework convention on tobacco control negotiations, Health Policy, 100:107-115). PMID- 21983012 TI - Endoplasmic reticulum stress-induced CHOP activation mediates the down-regulation of leptin in human neuroblastoma SH-SY5Y cells treated with the oxysterol 27 hydroxycholesterol. AB - Epidemiological studies have suggested an inverse relationship between the adipocytokine leptin and the onset of Alzheimer's disease (AD), and leptin supplementation decreases amyloid-beta (Abeta) production and tau phosphorylation (p-tau), two major biochemical events that play a key role in the pathogenesis of AD. We have previously shown that the cholesterol oxidized product 27 hydroxycholesterol (27-OHC) inhibits leptin expression, an effect that correlated with increased levels of Abeta and p-tau. We have also shown that 27-OHC induces endoplasmic reticulum (ER) stress, a cellular response that is implicated in AD and confers leptin resistance. However the extent to which ER stress is involved in 27-OHC-induced attenuation in leptin expression has not been determined. In this study we determined the involvement of ER stress in the 27-OHC-induced attenuation of leptin expression in SH-SY5Y human neuroblastoma cells. We demonstrate that 27-OHC-induced ER stress attenuates leptin expression by activating C/EBP Homologous Protein (CHOP) which negatively regulates C/EBPalpha, a transcription factor required for leptin expression. The molecular chaperone 4 phenylbutyric acid (4-PBA) precludes 27-OHC-evoked ER stress and down-regulation of leptin. Furthermore, we demonstrate that the activation of the transcription factor CHOP in response to ER stress is pivotal in the attenuation of leptin expression as knocking-down CHOP alleviates the attenuation in leptin expression. Our study implicates ER stress as the mechanistic link in the 27-OHC-induced negative regulation of leptin, a hormone that has potential therapeutic effects in AD by reducing Abeta and phosphorylated tau accumulation. PMID- 21983013 TI - Mitochondrial localization unveils a novel role for GRK2 in organelle biogenesis. AB - Metabolic stimuli such as insulin and insulin like growth factor cause cellular accumulation of G protein coupled receptor kinase 2 (GRK2), which in turn is able to induce insulin resistance. Here we show that in fibroblasts, GRK2 is able to increase ATP cellular content by enhancing mitochondrial biogenesis; also, it antagonizes ATP loss after hypoxia/reperfusion. Interestingly, GRK2 is able to localize in the mitochondrial outer membrane, possibly through one region within the RGS homology domain and one region within the catalytic domain. In vivo, GRK2 removal from the skeletal muscle results in reduced ATP production and impaired tolerance to ischemia. Our data show a novel sub-cellular localization of GRK2 in the mitochondria and an unexpected role in regulating mitochondrial biogenesis and ATP generation. PMID- 21983014 TI - Dimethylcelecoxib induces an inhibitory complex consisting of HDAC1/NF kappaB(p65)RelA leading to transcriptional downregulation of mPGES-1 and EGR1. AB - Dimethylcelecoxib, a non-COX-2 inhibiting derivative of celecoxib, inhibits PGE(2) synthesis by transcriptional inhibition of mPGES-1. Previously we demonstrated that DMC downregulates EGR1 expression and increases nuclear NF kappaB in human cervical cancer cells (HeLa). Both transcription factors are important regulators of mPGES-1 expression. Here we show that treatment of HeLa cells with DMC inhibits EGR1 promoter activity by influencing the transactivation activity of NF-kappaB. Mutation of the NF-kappaB motif as well as downregulation of NF-kappaB(p65)RelA using siRNA repealed the inhibitory effect of DMC on the EGR1 promoter. The transactivation activity of NF-kappaB is regulated by various co-activators or co-repressors. One of these co-repressors is HDAC1. DMC did not influence HDAC1 expression, but the HDAC activity was enhanced under DMC influence. After DMC treatment NF-kappaB co-immunoprecipitated with HDAC1. Electromobility shift assays depicted an increased interaction between NF-kappaB HDAC1 and DNA containing NF-kappaB binding motives. Performing CHIP-assays we finally demonstrated the interaction of NF-kappaB and HDAC1 at the EGR1 promoter that was in part reversed by the HDAC1 inhibitor trichostatin A. Using siRNA against HDAC1 we could repeal the inhibitory effect of DMC on the EGR1 promoter. In conclusion we demonstrated that treatment of HeLa cells with DMC leads to an enhanced formation of a complex consisting of NF-kappaB and HDAC1 that binds to the EGR1 promoter resulting in downregulation of EGR1 expression which plays a major role for transcriptional inhibition of mGPES-1 expression. How these effects of DMC may contribute to a potential therapeutical benefit of various diseases is discussed. PMID- 21983015 TI - Structural basis for specificity of TGFbeta family receptor small molecule inhibitors. AB - Transforming growth factor-beta (TGFbeta) receptor kinase inhibitors have a great therapeutic potential. SB431542 is one of the mainly used kinase inhibitors of the TGFbeta/Activin pathway receptors, but needs improvement of its EC(50) (EC(50)=1 MUM) to be translated to clinical use. A key feature of SB431542 is that it specifically targets receptors from the TGFbeta/Activin pathway but not the closely related receptors from the bone morphogenic proteins (BMP) pathway. To understand the mechanisms of this selectivity, we solved the crystal structure of the TGFbeta type I receptor (TbetaRI) kinase domain in complex with SB431542. We mutated TbetaRI residues coordinating SB431542 to their counterparts in activin-receptor like kinase 2 (ALK2), a BMP receptor kinase, and tested the kinase activity of mutated TbetaRI. We discovered that a Ser280Thr mutation yielded a TbetaRI variant that was resistant to SB431542 inhibition. Furthermore, the corresponding Thr283Ser mutation in ALK2 yielded a BMP receptor sensitive to SB431542. This demonstrated that Ser280 is the key determinant of selectivity for SB431542. This work provides a framework for optimising the SB431542 scaffold to more potent and selective inhibitors of the TGFbeta/Activin pathway. PMID- 21983016 TI - Random alloy-like local structure of Fe(Se, S)(1-x)Te(x) superconductors revealed by extended x-ray absorption fine structure. AB - The local structure of Fe(Se, S)(1-x)Te(x) ternary (11-type) chalcogenides has been studied by temperature dependent Fe K-edge extended x-ray absorption fine structure measurements. We find that the Fe-Se and Fe-Te distances in ternary FeSe(1-x)Te(x) are closer to the respective distances in the binary systems, revealing significant divergence of the local structure from the average one. The mean square relative displacements show a systematic change with Te content, consistent with bond relaxation in the inhomogeneous ternary phases. Also, the Fe Te and Fe-S distances in the FeS(0.2)Te(0.8) ternary system are found to be different in the crystallographically homogeneous structure. The observed features are characteristic of ternary random alloys, suggesting that a proper consideration should be given to the atomic distribution for describing the complex electronic structure of these multi-band Fe-based chalcogenides. PMID- 21983017 TI - The slowest, the worst: demonstrating the evidence. PMID- 21983018 TI - Deep brain stimulation response in pathologically confirmed cases of multiple system atrophy. AB - Deep brain stimulation is a treatment for select cases of medication refractory movement disorders including Parkinson's disease. Deep brain stimulation has not been recommended for treatment in multiple system atrophy patients. However, the paucity of literature documenting the effects of deep brain stimulation in multiple system atrophy patients and the revelation of a levodopa responsive subtype of multiple system atrophy suggests further investigation is necessary. This study summarizes the positive and negative effects of deep brain stimulation treatment in two pathologically confirmed multiple system atrophy patients from the University of Florida Deep Brain Stimulation-Brain Tissue Network. Clinical diagnosis for the two patient cases did not match the neuropathological diagnosis. We noted that in both pathologically confirmed multiple system atrophy patients, death occurred as a result of myocardial infarction. Importantly, there was reported transient benefit in levodopa responsive features that indicate deep brain stimulation may be an option for select multiple system atrophy patients. PMID- 21983019 TI - Impulse control disorders and depression in Finnish patients with Parkinson's disease. AB - INTRODUCTION: Impulse control disorders occur frequently in patients with Parkinson's disease. However, the frequencies have been investigated mainly in patients from secondary or tertiary care centers, and thus, the prevalence rates in general community are not known. OBJECTIVE: Our objective was to study the prevalence rates of impulse control disorders and related factors in a large, non selected sample of Parkinson's disease patients. METHODS: We conducted a cross sectional survey among Parkinson's disease patients from Finnish Parkinson Association [n = 575; 365 men, 240 women, median age 64 (range 43-90) years]. Problem and pathological gambling were estimated with the South Oaks Gambling Screen, risk for impulse control disorders with the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease, and depression with the Beck Depression Inventory. RESULTS: The frequency of pathological gambling was 7.0%. The overall frequency of a positive screen for an impulse control disorder was 34.8%, and 12.5% of the patients screened positive for multiple disorders. Depressive symptoms were statistically the most important factor in explaining variance in impulse control disorder risk, even more than sex, age, age of disease onset, alcohol use, or medication. CONCLUSIONS: The high proportion of patients screened positive for impulse control disorders in a non-selected sample emphasize the importance of routine screening of these disorders in Parkinson's disease. Pathological gambling prevalence in Parkinson's disease is seven times higher than in the general population in Finland. The results underline the importance of depression in impulse control disorders associated with Parkinson's disease. PMID- 21983020 TI - High-content screening of peptide-based non-viral gene delivery systems. AB - High-content screening (HCS) uses high-capacity automated fluorescence imaging for the quantitative analysis of single cells and cell populations. Here, we developed an HCS assay for rapid screening of non-viral gene delivery systems as exemplified by the screening of a small library of peptide-based transfectants. These peptides were simultaneously screened for transfection efficiency, cytotoxicity, induction of cell permeability and the capacity to transfect non dividing cells. We demonstrated that HCS is a valuable extension to the already existing screening methods for the in vitro evaluation of non-viral gene delivery systems with the added value that multiple parameters can be screened in parallel thereby obtaining more information from a single screening event, which will accelerate the development of novel gene delivery systems. PMID- 21983021 TI - Polarized osteoclasts put marks of tartrate-resistant acid phosphatase on dentin slices--a simple method for identifying polarized osteoclasts. AB - Osteoclasts form ruffled borders and sealing zones toward bone surfaces to resorb bone. Sealing zones are defined as ringed structures of F-actin dots (actin rings). Polarized osteoclasts secrete protons to bone surfaces via vacuolar proton ATPase through ruffled borders. Catabolic enzymes such as tartrate resistant acid phosphatase (TRAP) and cathepsin K are also secreted to bone surfaces. Here we show a simple method of identifying functional vestiges of polarized osteoclasts. Osteoclasts obtained from cocultures of mouse osteoblasts and bone marrow cells were cultured for 48 h on dentin slices. Cultures were then fixed and stained for TRAP to identify osteoclasts on the slices. Cells were removed from the slices with cotton swabs, and the slices subjected to TRAP and Mayer's hematoxylin staining. Small TRAP-positive spots (TRAP-marks) were detected in the resorption pits stained with Mayer's hematoxylin. Pitted areas were not always located in the places of osteoclasts, but osteoclasts existed on all TRAP-marks. A time course experiment showed that the number of TRAP-marks was maintained, while the number of resorption pits increased with the culture period. The position of actin rings formed in osteoclasts corresponded to that of TRAP-marks on dentin slices. Immunostaining of dentin slices showed that both cathepsin K and vacuolar proton ATPase were colocalized with the TRAP-marks. Treatment of osteoclast cultures with alendronate, a bisphosphonate, suppressed the formation of TRAP-marks and resorption pits without affecting the cell viability. Calcitonin induced the disappearance of both actin rings and TRAP marks in osteoclast cultures. These results suggest that TRAP-marks are vestiges of proteins secreted by polarized osteoclasts. PMID- 21983022 TI - Functionalization of deproteinized bovine bone with a coating-incorporated depot of BMP-2 renders the material efficiently osteoinductive and suppresses foreign body reactivity. AB - The repair of critical-sized bony defects remains a challenge in the fields of implantology, maxillofacial surgery and orthopaedics. As an alternative bone defect filler to autologous bone grafts, deproteinized bovine bone (DBB) is highly osteoconductive and clinically now widely used. However, this product suffers from the disadvantage of not being intrinsically osteoinductive. In the present study, this property was conferred by coating DBB with a layer of calcium phosphate into which bone morphogenetic protein 2 (BMP-2) was incorporated. Granules of DBB bearing a coating-incorporated depot of BMP-2--together with the appropriate controls (DBB bearing a coating but no BMP-2; uncoated DBB bearing adsorbed BMP-2; uncoated DBB bearing no BMP-2)--were implanted subcutaneously in rats. Five weeks later, the implants were withdrawn for a histomorphometric analysis of the volume densities of (i) bone, (ii) bone marrow, (iii) foreign body giant cells and (iv) fibrous capsular tissue. Parameters (i) and (ii) were highest, whilst parameters (iii) and (iv) were lowest in association with DBB bearing a coating-incorporated depot of BMP-2. Hence, this mode of functionalization not only confers DBB with the property of osteoinductivity but also improves its biocompatibility--thus dually enhancing its clinical potential in the repair of bony defects. PMID- 21983023 TI - Geant4-Simulations for cellular dosimetry in nuclear medicine. AB - The application of unsealed radionuclides in radiobiological experiments can lead to intracellular radionuclide uptake and an increased absorbed dose. Accurate dose quantification is essential to assess observed radiobiological effects. Due to small cellular dimensions direct dose measurement is impossible. We will demonstrate the application of Monte Carlo simulations for dose calculation. Dose calculations were performed using the Geant4 Monte Carlo toolkit, wherefore typical experimental situations were designed. Dose distributions inside wells were simulated for different radionuclides. S values were simulated for spherical cells and cell monolayers of different diameter. Concomitantly experiments were performed using the PC Cl3 cell line with mediated radionuclide uptake. For various activity distributions cellular survival was measured. We yielded S values for dose distribution inside the wells. Calculated S values for a single cell are in good agreement to S values provided in the literature (ratio 0.87 to 1.07). Cross-dose is up to ten times higher for Y-90. Concomitantly performed cellular experiments confirm the dose calculation. Furthermore the necessity of correct dose calculation was shown for assessment of radiobiological effects after application of unsealed radionuclides. Thereby the feasibility of using Geant4 was demonstrated. PMID- 21983024 TI - GATE based Monte Carlo simulation of planar scintigraphy to estimate the nodular dose in radioiodine therapy for autonomous thyroid adenoma. AB - The recommended target dose in radioiodine therapy of solitary hyperfunctioning thyroid nodules is 300-400Gy and therefore higher than in other radiotherapies. This is due to the fact that an unknown, yet significant portion of the activity is stored in extranodular areas but is neglected in the calculatory dosimetry. We investigate the feasibility of determining the ratio of nodular and extranodular activity concentrations (uptakes) from post-therapeutically acquired planar scintigrams with Monte Carlo simulations in GATE. The geometry of a gamma camera with a high energy collimator was emulated in GATE (Version 5). A geometrical thyroid-neck phantom (GP) and the ICRP reference voxel phantoms "Adult Female" (AF, 16ml thyroid) and "Adult Male" (AM, 19ml thyroid) were used as source regions. Nodules of 1ml and 3ml volume were placed in the phantoms. For each phantom and each nodule 200 scintigraphic acquisitions were simulated. Uptake ratios of nodule and rest of thyroid ranging from 1 to 20 could be created by summation. Quantitative image analysis was performed by investigating the number of simulated counts in regions of interest (ROIs). ROIs were created by perpendicular projection of the phantom onto the camera plane to avoid a user dependant bias. The ratio of count densities in ROIs over the nodule and over the contralateral lobe, which should be least affected by nodular activity, was taken to be the best available measure for the uptake ratios. However, the predefined uptake ratios are underestimated by these count density ratios: For an uptake ratio of 20 the count ratios range from 4.5 (AF, 1ml nodule) to 15.3 (AM, 3ml nodule). Furthermore, the contralateral ROI is more strongly affected by nodular activity than expected: For an uptake ratio of 20 between nodule and rest of thyroid up to 29% of total counts in the ROI over the contralateral lobe are caused by decays in the nodule (AF 3 ml). In the case of the 1ml nodules this effect is smaller: 9-11% (AF) respectively 7-8% (AM). For each phantom, the dependency of count density ratios upon uptake ratios can be modeled well by both linear and quadratic regression (quadratic: r(2)>0.99), yielding sets of parameters which in reverse allow the computation of uptake ratios (and thus dose) from count density ratios. A single regression model obtained by fitting the data of all simulations simultaneously did not provide satisfactory results except for GP, while underestimating the true uptake ratios in AF and overestimating them in AM. The scintigraphic count density ratios depend upon the uptake ratios between nodule and rest of thyroid, upon their volumes, and their respective position in a non-trivial way. Further investigations are required to derive a comprehensive rule to calculate the uptake or dose ratios based on post therapeutic scintigraphy. PMID- 21983025 TI - Preparation and characterization of nano-hydroxyapatite/chitosan cross-linking composite membrane intended for tissue engineering. AB - In this paper, a series of nano-hydroxyapatite(n-HA)/chitosan cross-linking composite membranes (n-HA; 0, 5, 10, 15, 20 and 30 wt%) were successfully developed by a simple casting/solvent evaporation method. n-HA with size about 20 nm in vertical diameter and about 100 nm in horizontal diameter was successfully synthesized by a hydro-thermal precipitation method, and then dispersed into chitosan/genipin solution with the aid of continuous ultrasound to develop n HA/chitosan cross-linking composite membranes. The detailed characterizations including Fourier transform infrared spectroscopy (FTIR), X-ray diffractometer (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), water adsorption and tensile test were performed. With the analysis of FTIR spectra and TGA spectra, it suggested that there was existence of possible interactions between polymer and n-HA. Meanwhile, the n-HA content was greatly effected on the morphology as well as the tensile property of composite membrane. In vitro cytotoxicity test suggested that the developed n-HA/chitosan cross linking composite membrane was non-cytotoxicity against L929 cells after 24h's incubation might be suitable for further in vivo application. PMID- 21983026 TI - Balanced electrostatic blending approach--an alternative to chemical crosslinking of Thai silk fibroin/gelatin scaffold. AB - In tissue engineering, chemical crosslinking is widely used for conjugating two or more biomaterials to mainly control biodegradability and strength. For example, Thai silk fibroin/gelatin scaffold will offer mechanical strength from Thai silk fibroin and cell attraction from gelatin. However, chemical crosslinking requires crosslinking agent which could potentially pose negative impact from remaining trace amount of chemicals especially in medical application. Here we present an alternative approach to chemical crosslinking-a balance electrostatic blending approach. In this approach, two opposite charge biomaterials were selected for blending, with different ratios. Both materials were bound together with electrostatic force. The maximum binding was achieved when mixture electric potential approaches zero. In this work, we compared this approach with traditionally chemical crosslinking in terms of physical appearance, binding effectiveness, mechanical strength (in dry/wet conditions), in vitro biodegradation, and cell proliferation. We found that 50/50 weight ratio of Thai silk fibroin/gelatin scaffold had almost comparable properties to chemical crosslinked scaffold. It has similar appearance, binding effectiveness, and affinity for cell proliferation. For mechanical properties, even this approach yields lower dry compressive modulus compared with chemical crosslinking. But in wet condition, the compressive modulus from both methods is similar. However, the biodegradation time of non-crosslinked scaffolds is slightly faster than that of chemical crosslinked ones. These results demonstrate that a balance electrostatic approach is an alternative approach to chemical crosslinking when there is a concern of remaining trace amount of crosslinking agent in medical application. PMID- 21983027 TI - Anti-fatigue activity of polysaccharides extract from Radix Rehmanniae Preparata. AB - The anti-fatigue effects of the Radix Rehmanniae Preparata polysaccharides (RRPP) were studied in mice. The RRPP were orally administered at doses of 50, 100 and 200 mg/kg for 4 weeks and the anti-fatigue activity was evaluated using a weight loaded swimming test, along with the determination of serum urea nitrogen (SUN), hepatic glycogen and blood lactic acid (BLA) contents. The results showed that there was no significant difference in the body weight of mice in the three RRPP groups compared with the negative control group during initial, intermediate and terminal stages in the experiment (p>0.05). The ratio of exhausting swimming time was obviously increased 31.48% (p<0.05) and 61.51% (p<0.01) in the middle-dose group and the high-dose RRPP group, respectively. The BLA and SUN levels were decreased in middle-dose and high-dose RRPP groups (p<0.01). Hepatic glycogen level was increased in three RRPP treated groups (p<0.01). Therefore, RRPP may be responsible for the pharmacological effect of anti-fatigue of Radix Rehmanniae Preparata. The mechanism was related to the increase of the storage of hepatic glycogen and the decrease of the accumulation of SUN and BLA. PMID- 21983028 TI - Protective effects of sulfated chitooligosaccharides against hydrogen peroxide induced damage in MIN6 cells. AB - Sulfated chitooligosaccharides (COS-S) with different degrees of substitution (DS) were obtained by the chlorosulfuric acid/pyridine method. Protective effects of COS-S against hydrogen peroxide (H(2)O(2))-induced damage were investigated in pancreatic beta-cells MIN6 cell line. The cell viability, morphology, insulin contents, malondialdehyde (MDA) inhibition, lactate dehydrogenase (LDH) release and the levels of antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidise (GPx) were evaluated under oxidative damage by 150 MUM H(2)O(2) for 6h. COS-S did not show any harmful or inhibitory effect on cell growth at concentrations ranging from 0.1 to 0.5 mg/ml. While COS S could enhance the cell viability, decrease the production of ROS, and reduce the MDA level as well as LDH level in oxidative damaged beta-cells by being an antioxidant. The underlining mechanisms of protective effects of COS-S are partly due to the enhancement of antioxidant enzyme activity and inhibition of intracellular ROS production, along with suppressing MIN6 cell apoptosis subsequent to the amelioration of ROS. Moreover, increased DS might contribute to the defense mechanisms against H(2)O(2)-induced oxidative damage in MIN6 cells. These results indicated that the antioxidant properties of COS-S hold great potential for the oxidative diseases treatment, and the sulfate content of polysaccharides made great role in regulating antioxidant activities. PMID- 21983029 TI - Pharmacokinetics of bisphenol A in neonatal and adult CD-1 mice: inter-species comparisons with Sprague-Dawley rats and rhesus monkeys. AB - Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA metabolites in urine of >90% of Americans aged 6-60 suggests ubiquitous and frequent exposure at levels largely below 1 MUg/kg bw/d. The current study used LC/MS/MS to measure serum pharmacokinetics of unconjugated (active) and conjugated (inactive) BPA in adult and neonatal CD-1 mice by oral and subcutaneous (SC) injection routes. Deuterated BPA was used to avoid issues of background contamination. Significant inverse relationships were observed between postnatal age and measures of internal exposures (C(max)) to unconjugated BPA after oral administration. Phase II conjugation, area under the time concentration curve (AUC), and elimination half-time of unconjugated BPA were also inversely related to age. In postnatal day (PND) 3 mice, the combination of under-developed Phase II metabolism, rapid absorption, and slow elimination kinetics led to equivalent internal exposures for unconjugated BPA from oral and SC routes; however, maturing metabolic capabilities in PND 10 and older mice, led to large and significant route effects. The significant inverse age-related developmental profiles from PND 3 through adulthood for unconjugated BPA internal exposure metrics from oral administration to CD-1 mice and Sprague-Dawley rats were remarkably similar; however, the developmental profile was quite different for neonatal rhesus monkeys in which small insignificant age-related differences were observed. These results suggest that an adverse effect from BPA observed in rodent models, attributable to exposure during a discrete time period of neonatal development, would be less likely for comparable neonatal primate dosing based on internal dosimetry. On the other hand in all adults of all species studied, including humans, a low oral dose of BPA produced similarly small internal exposures for the unconjugated form, reflecting the dominant effect of presystemic Phase II metabolism. PMID- 21983030 TI - Translating cell polarity into tissue elongation. AB - Planar cell polarity, the orientation of single-cell asymmetries within the plane of a multicellular tissue, is essential to generating the shape and dimensions of organs and organisms. Planar polarity systems align cell behavior with the body axes and orient the cellular processes that lead to tissue elongation. Using Drosophila as a model system, significant progress has been made toward understanding how planar polarity is generated by biochemical and mechanical signals. Recent studies using time-lapse imaging reveal that cells engage in a number of active behaviors whose orientation and dynamics translate planar cell polarity into tissue elongation. Here we review recent progress in understanding the cellular mechanisms that link planar polarity to large-scale changes in tissue structure. PMID- 21983031 TI - 14-3-3 proteins as potential therapeutic targets. AB - The 14-3-3 family of phosphoserine/phosphothreonine-binding proteins dynamically regulates the activity of client proteins in various signaling pathways that control diverse physiological and pathological processes. In response to environmental cues, 14-3-3 proteins orchestrate the highly regulated flow of signals through complex networks of molecular interactions to achieve well controlled physiological outputs, such as cell proliferation or differentiation. Accumulating evidence now supports the concept that either an abnormal state of 14-3-3 protein expression, or dysregulation of 14-3-3/client protein interactions, contributes to the development of a large number of human diseases. In particular, clinical investigations in the field of oncology have demonstrated a correlation between upregulated 14-3-3 levels and poor survival of cancer patients. These studies highlight the rapid emergence of 14-3-3 proteins as a novel class of molecular target for potential therapeutic intervention. The current status of 14-3-3 modulator discovery is discussed. PMID- 21983032 TI - Stereoselective urinary MDMA (ecstasy) and metabolites excretion kinetics following controlled MDMA administration to humans. AB - The R- and S-enantiomers of racemic 3,4-methylenedioxymethamphetamine (MDMA) exhibit different dose-concentration curves. In plasma, S-MDMA was eliminated at a higher rate, most likely due to stereoselective metabolism. Similar data were shown in various in vitro experiments. The aim of the present study was the in vivo investigation of stereoselective elimination of MDMA's phase I and phase II metabolites in human urine following controlled oral MDMA administration. Urine samples from 10 participants receiving 1.0 and 1.6 mg/kg MDMA separated by at least one week were analyzed blind by liquid chromatography-high resolution-mass spectrometry and gas chromatography-mass spectrometry after chiral derivatization with S-heptafluorobutyrylprolyl chloride. R/S ratios at C(max) were comparable after low and high doses with ratios >1 for MDMA, free DHMA, and HMMA sulfate, and with ratios <1 for MDA, free HMMA, DHMA sulfate and HMMA glucuronide. In the five days after the high MDMA dose, a median of 21% of all evaluated compounds were excreted as R-stereoisomers and 17% as S-stereoisomers. Significantly greater MDMA, DHMA, and HMMA sulfate R-enantiomers and HMMA and HMMA glucuronide S-stereoisomers were excreted. No significant differences were observed for MDA and DHMA sulfate stereoisomers. Changes in R/S ratios could be observed over time for all analytes, with steady increases in the first 48 h. R/S ratios could help to roughly estimate time of MDMA ingestion and therefore, improve interpretation of MDMA and metabolite urinary concentrations in clinical and forensic toxicology. PMID- 21983033 TI - 7beta-Hydroxycholesterol-induced energy stress leads to sequential opposing signaling responses and to death of C6 glioblastoma cells. AB - 7beta-Hydroxycholesterol cytotoxicity has been shown in vivo and in vitro to be dependent on the accumulation of its esters. We show in our study, using a detergent-free raft preparation and LC/MS lipid content analysis, that membrane microdomains isolated from 7beta-hydroxycholesterol-treated C6 cells have a reduced cholesterol: cholesterol ester ratio and accumulate 7keto hydroxycholesterol, 7beta-hydroxycholesterol and 7beta-hydroxycholesterol esters. These modifications in lipid content are accompanied by a redistribution of flotillin-1 in the lipid rafts. Transient increases of AMPK phosphorylation and mitochondrial activity during the first 12 h of 7beta-hydroxycholesterol treatment indicate that C6 cells undergo energy stress and increase oxidative phosphorylation. Even so, ATP levels are maintained during 15 h until glucose uptake decreases. The cell's answers to raft modifications and energy stress are sequential activations of different signaling pathways such as ERK, AMPK and PI3K/Akt. These pathways, known to be activated under energy stress conditions, are transiently activated at 6 h (ERK, AMPK) and 12 h (Akt) of treatment respectively suggesting a shift from cell survival to cell proliferation. The persistence of 7beta-hydroxycholesterol-induced stress led after 24 h to P38 activation, loss of GSK3beta activation and to cell death. Finally we demonstrate that the observed signaling responses depend on 7beta-hydroxycholesterol esterification, confirming that esterification of 7beta-hydroxycholesterol is essential for cytotoxicity. PMID- 21983034 TI - Consideration of allosterism and interacting proteins in the physiological functions of the serotonin transporter. AB - The serotonin transporter (SERT) functions to transport serotonin (5-HT) from the extracellular space into neurons to maintain homeostatic control of 5-HT. It is the molecular target for selective serotonin reuptake inhibitor (SSRI) antidepressants. Preclinical research has shown that some SERT inhibitors can bind to two distinct binding sites on the SERT, a primary high affinity binding site and a low affinity allosteric binding site. Mutational studies of the SERT and computational modeling methods with escitalopram resulted in the identification of key amino acid residues important for the function of the allosteric binding site. While this allosteric binding site appears to influence the clinical efficacy of escitalopram under physiological conditions, the molecular mechanism of this effect is still poorly understood and may involve a large network of protein-protein interactions with the SERT. Dynamic interfaces between the SERT and the SERT interacting proteins (SIPs) potentially influence not only the SERT on its uptake function, its regulation, and trafficking, but also on known as well as yet to be identified non-canonical signaling pathways through SIPs. In this commentary, we outline approaches in the areas of selective small-molecule allosteric compound discovery, biochemistry, in vivo genetic knock in mouse models, as well as computational and structural biology. These studies of the intra-molecular allosteric modulation of the SERT in the context of the myriad of potential inter-molecular signaling interactions with SIPs may help uncover unknown physiological functions of the SERT. PMID- 21983035 TI - Robot-assisted laparoscopic repair of high vesicovaginal fistulae with peritoneal flap inlay. PMID- 21983036 TI - Volumetric and angiogenic evaluation of antitumor effects with acoustic liposome and high-frequency ultrasound. AB - Acoustic liposomes (AL) have their inherent echogenicity and can add functionality in serving as drug carriers with tissue specificity. Nonuniform vascular structures and vascular branches/bends are evaluated by imaging the intravascular movement locus of ALs with high-frequency ultrasound (HF-US) imaging. However, the evaluation of antitumor effects on angiogenesis by ALs and HF-US imaging has not been reported. Here, we show that the combination of ALs and an HF-US imaging system is capable of noninvasively evaluating antitumor volumetric and angiogenic effects in preclinical mouse models of various cancers. In this study, the antitumor effects of cisplatin on tumor growth and angiogenesis in mice bearing two different types of tumor cells were assessed. By tracking each AL flowing in the vessel and transferring the images to personal computers, microvessel structures were mapped and reconstructed using the color difference based on SD method. The antitumor effects were confirmed with an in vivo bioluminescence imaging system and immunohistochemical analysis. Our results show that cisplatin inhibits tumor growth by decreasing intratumoral vessel area but does not affect the angiogenesis ratio in the tumor. The vascular occupancy in the outer region of the tumor was larger than that in the inner region; however, both occupancies were similar to those of the control tumor. We propose that this method of mapping microvessels with ALs and an HF-US system can serve as a new molecular imaging method for the assessment of angiogenesis and can be applied to evaluate the antitumor effects by various therapeutic agents. PMID- 21983037 TI - Multiple stress signals activate mutant p53 in vivo. AB - p53 levels are tightly regulated in normal cells, and thus, the wild-type p53 protein is nearly undetectable until stimulated through a variety of stresses. In response to stress, p53 is released from its negative regulators, mainly murine double minute 2 (Mdm2), allowing p53 to be stabilized to activate cell-cycle arrest, senescence, and apoptosis programs. Many of the upstream signals that regulate wild-type p53 are known; however, limited information for the regulation of mutant p53 exists. Previously, we showed that wild-type and mutant p53R172H are regulated in a similar manner in the absence of Mdm2 or p16. In addition, this stabilization of mutant p53 is responsible for the gain-of-function metastatic phenotype observed in the mouse. In this report, we examined the role of oncogenes, DNA damage, and reactive oxygen species, signals that stabilize wild-type p53, on the stabilization of mutant p53 in vivo and the consequences of this expression on tumor formation and survival. These factors stabilized mutant p53 protein which oftentimes contributed to exacerbated tumor phenotypes. These findings, coupled with the fact that patients carry p53 mutations without stabilization of p53, suggest that personalized therapeutic schemes may be needed for individual patients depending on their p53 status. PMID- 21983038 TI - Polybrominated diphenyl ethers and their methoxylated analogs in mullet (Mugil cephalus) and sea bass (Dicentrarchus labrax) from Bizerte Lagoon, Tunisia. AB - Concentrations of ten polybrominated diphenyl ethers (PBDEs) and eight methoxylated polybrominated diphenyl ethers (MeO-PBDEs) in mullet (Mugil cephalus) and sea bass (Dicentrarchus labrax) collected from the Bizerte Lagoon and the Mediterranean Sea were investigated. To the best of our knowledge, this is the first report of these compounds in marine fishes from Tunisia. The PBDE mean concentrations in fish from Bizerte Lagoon were 45.3 and 96.2 ng g(-1) lw respectively in mullet and sea bass, while the concentrations of these compounds in mullet and sea bass from Mediterranean Sea were 7.80 and 27.9 ng g(-1) lw respectively. MeO-PBDE concentrations in mullet and sea bass from Bizerte Lagoon ranged from 6.46 to 286 ng g(-1) lw and from 49.4 to 798 ng g(-1) lw respectively, while the concentrations of these compounds in mullet and sea bass from Mediterranean Sea ranged from 190 to 401 ng g(-1) lw and from 353 to 578 ng g(-1) lw respectively. The total PBDEs and total MeO-PBDEs concentration in fish from Bizerte Lagoon were similar or slightly lower than those reported for other species from other locations around the world. PMID- 21983039 TI - Independence through social networks: bridging potential among older women and men. AB - OBJECTIVES: Most studies of older adults' social networks focus on their access to dense networks that yield access to social support. This paper documents gender differences in the extent to which older adults maintain a related, but distinct, form of social capital-bridging potential, which involves serving as a tie between two unconnected parties and thus boosts independence and control of everyday social life. METHODS: I use egocentric social network data from a national sample of 3,005 older adults--collected in 2005-2006 by the National Social Life, Health, and Aging Project--to compare older men's and women's network bridging potential using multivariate regression analysis. RESULTS: Older women are more likely than older men to have bridging potential in their networks between both kin and non-kin contacts. These gender differences increase with age. Older women are also more likely to have network members who are not connected to or monopolized by their spouse or partner. Some, but not all, of these gender differences are due to the fact that older women have larger social networks and maintain more ties to people outside of the household. DISCUSSION: These findings raise important questions about the relational advantages older women have over older men, including greater autonomy, and contradict stereotypes about women having more closely knit, kin-centered networks than men. PMID- 21983040 TI - Health behavior change following chronic illness in middle and later life. AB - OBJECTIVES: Understanding lifestyle improvements among individuals with chronic illness is vital for targeting interventions that can increase longevity and improve quality of life. METHODS: Data from the U.S. Health and Retirement Study were used to examine changes in smoking, alcohol use, and exercise 2-14 years after a diagnosis of heart disease, diabetes, cancer, stroke, or lung disease. RESULTS: Patterns of behavior change following diagnosis indicated that the vast majority of individuals diagnosed with a new chronic condition did not adopt healthier behaviors. Smoking cessation among those with heart disease was the largest observed change, but only 40% of smokers quit. There were no significant increases in exercise for any health condition. Changes in alcohol consumption were small, with significant declines in excessive drinking and increases in abstention for a few health conditions. Over the long term, individuals who made changes appeared to maintain those changes. Latent growth curve analyses up to 14 years after diagnosis showed no average long-term improvement in health behaviors. DISCUSSION: Results provide important new information on health behavior changes among those with chronic disease and suggest that intensive efforts are required to help initiate and maintain lifestyle improvements among this population. PMID- 21983042 TI - Vision deficits precede structural losses in a mouse model of mitochondrial dysfunction and progressive retinal degeneration. AB - Current animal models of retinal disease often involve the rapid development of a retinal disease phenotype; however, this is at odds with age-related diseases that take many years to manifest clinical symptoms. The present study was performed to examine an apoptosis-inducing factor (Aif)-deficient model, the harlequin carrier mouse (X(hq)X), and determine how mitochondrial dysfunction and subsequent accelerated aging affect the function and structure of the mouse retina. Vision and eye structure for cohorts of 6 X(hq)X and 6 wild type mice at 3, 11, and 15 months of age were studied using in vivo electroretinography (ERG), and optical coherence tomography (OCT). Retinal superoxide levels were determined in situ using dihydroethidium (DHE) histochemistry. Retinal cell counts were quantified post mortem using hematoxylin and eosin (H&E) staining. ERG analysis of X(hq)X retinal function indicated a reduction in b-wave amplitude significant at 3 months of age (p < 0.05), declining further with age. However, retinal neuron counts demonstrated the absence of physical degeneration at 3 and 11 months of age despite significant reduction in ERG b-wave amplitude. Superoxide anion levels were elevated in the ganglion cell, inner nuclear and outer nuclear layers of the retina (p < 0.01, p < 0.01, and p < 0.001, respectively) of 11 month-old X(hq)X mice in comparison to wild type, preceding the structural losses observed at 15 mos. Early onset of retinal function deficits occurred independently of neuron loss. Changes in neurotransmitter localization in the stressed retina may account for the early and significant reduction in retinal function. This remodeling of retinal neurochemistry in response to stress may be a relevant mechanism in the progression of normal retinal aging and early stages of some retinal degenerative diseases. PMID- 21983041 TI - Dynamic testing of regional viscoelastic behavior of canine sclera. AB - Intraocular pressure (IOP) fluctuations have gained recent clinical interest and thus warrant an understanding of how the sclera responds to dynamic mechanical insults. The objective of this study was to characterize the regional dynamic viscoelastic properties of canine sclera under physiological cyclic loadings. Scleral strips were excised from the anterior, equatorial, and posterior sclera in ten canine eyes. The dimensions of each strip were measured using a high resolution ultrasound imaging system. The strips were tested in a humidity chamber at approximately 37 degrees C using a Rheometrics Systems Analyzer. A cyclic strain input (0.25%, 1 Hz) was applied to the strips, superimposed upon pre-stresses corresponding to an IOP of 15, 25, and 45 mmHg. The cyclic stress output was recorded and the dynamic properties were calculated based on linear viscoelasticity. Uni-axial tensile tests were also performed on the same samples and the results were compared to those reported for human eyes. The results showed that the sclera's resistance to dynamic loading increased significantly while the damping capability decreased significantly with increasing pre-stresses for all regions of sclera (P < 0.001). Anterior sclera appeared to have a significantly higher damping capability than equatorial and posterior sclera (P = 0.003 and 0.018, respectively). The secant modulus from uni-axial tensile tests showed a decreasing trend from anterior to posterior sclera, displaying a similar pattern as in the human eye. In conclusion, all scleral regions in the canine eyes exhibited an increased ability to resist and a decreased ability to dampen cyclic stress insults at increasing pre-stress (i.e., increasing steady-state IOP). The regional variation of the dynamic properties differed from those of uni axial tensile tests. Dynamic testing may provide useful information to better understand the mechanical behavior of the sclera in response to dynamic IOP. PMID- 21983043 TI - Is hip muscle strength the key to walking as a bilateral amputee, whatever the level of the amputations? AB - BACKGROUND: Little data have been reported on the factors that are important in bilateral amputee walking ability especially the role of hip strength. STUDY DESIGN: Observational, case-control study where participants were evaluated at a single point in time. OBJECTIVES: The aim of this study was to investigate the factors involved in bilateral amputee walking ability by assessment of walking speed, perceived exertion, exercise intensity, physiological cost index (PCI) and hip muscle strength. METHODS: For a group of 10 bilateral amputees, with different levels of amputation, and a non-pathological reference group, walking ability was assessed using the two-minute walk test. Hip muscle strength was assessed using isokinetic strength tests. RESULTS: Bilateral amputees were found to have slower walking speeds and increased PCI of walking which were correlated to higher levels of amputation. Peak hip torques were reduced in the amputees, which was only significant for concentric extension torque (p = 0.029), and approaching significance for concentric flexion (p = 0.061) and abduction (p = 0.057). Bilateral amputee peak hip strength suggested a positive trend with increasing walking ability. CONCLUSIONS: Bilateral amputee walking ability was reduced and mainly related to level of amputation. The role of hip strength in bilateral amputee walking ability requires further investigation. PMID- 21983044 TI - Prosthetic rehabilitation of a patient with partial ear amputation using a self suspension technique. AB - BACKGROUND AND AIM: Partial ear amputations are one of the forms of ear loss. A user-friendly design of prosthesis with safe suspension and an aesthetic appearance can be helpful to a patient who has lost part of their ear due to congenital absence or trauma. Prosthetic use has social and psychological effects on the patient and their family. The aim of this paper is to describe a technique of ear prosthesis fabrication with self suspension for these patients. TECHNIQUE: To provide a snugly fitting prosthesis, the only parts of the residual ear that were covered by the prosthesis were accurately manufactured and reduced in thickness to 0.5-1 mm and 10 mm in width, so that the silicone extended over the stumps to provide adequate suspension. DISCUSSION: This paper proposes the designing and constructing of a silicone ear prosthesis which had good suspension, low cost, was easy to use and was acceptable in appearance to the patient. PMID- 21983045 TI - Psycho-markers of weight loss. The roles of TFEQ Disinhibition and Restraint in exercise-induced weight management. AB - Eating behaviour traits, namely Disinhibition and Restraint, have the potential to exert an effect on food intake and energy balance. The effectiveness of exercise as a method of weight management could be influenced by these traits. Fifty eight overweight and obese participants completed 12-weeks of supervised exercise. Each participant was prescribed supervised exercise based on an expenditure of 500 kcal/session, 5d/week for 12-weeks. Following 12-weeks of exercise there was a significant reduction in mean body weight (-3.26+/-3.63 kg), fat mass (FM: -3.26+/-2.64 kg), BMI (-1.16+/-1.17 kg/m(2)) and waist circumference (WC: -5.0+/-3.23 cm). Regression analyses revealed a higher baseline Disinhibition score was associated with a greater reduction in BMI and WC, while Internal Disinhibition was associated with a larger decrease in weight, %FM and WC. Neither baseline Restraint or Hunger were associated with any of the anthropometric markers at baseline or after 12-weeks. Furthermore, after 12-weeks of exercise, a decrease in Disinhibition and increase in Restraint were associated with a greater reduction in WC, whereas only Restraint was associated with a decrease in weight. Post-hoc analysis of the sub-factors revealed a decrease in External Disinhibition and increase in Flexible Restraint were associated with weight loss. However, an increase in Rigid Restraint was associated with a reduction in %FM and WC. These findings suggest that exercise induced weight loss is more marked in individuals with a high level of Disinhibition. These data demonstrate the important roles that Disinhibition and Restraint play in the relationship between exercise and energy balance. PMID- 21983046 TI - Dietary manipulations influence sucrose acceptance in diet induced obese mice. AB - The current studies examined the influence of a high fat diet on sucrose acceptance in diet induced obese (DIO) mice. C57BL/6J mice were placed on either a 45 kcal% fat diet (group DIO), or a control 10% kcal fat diet (group control) for 12 weeks followed by sucrose consumption tests and dietary manipulations. After 12 weeks exposure, body weights of DIO mice significantly exceeded those of the control mice. During subsequent sucrose consumption tests, DIO mice showed suppression in the total number of licks relative to controls. In a second experiment, consumption tests with water and a variety of sucrose concentrations revealed a hypophagic phenotype in naive DIO mice. Licking microstructure analyses were conducted on the licking behavior of all mice, which revealed a reduction in burst size and number for DIO mice. Subsequently, we examined whether 10 days exposure to regular lab chow would alter sucrose consumption and taste evaluation in DIO mice. As a result of this dietary switch, all mice showed comparable licking behavior suggesting that exposure to the high-fat diet and diet-induced obesity may reduce preferences for other tastants in C57BL/6J mice. PMID- 21983047 TI - Diet and anxiety. An exploration into the Orthorexic Society. AB - The modern food system has radically modified the social-anthropological framework that informs food choices. To explore factors that influence food choices within this modified framework, eight focus groups consisting of women 15 45 years old were conducted in Nova Scotia (Canada). Using a grounded theory approach, two main themes emerged centered around (1) perceptions of a changing culinary order that emphasizes individual dietary responsibility and decision making and (2) the confusion/anxiety experienced as participants try to assimilate the information generated by today's modern food system. Participants inextricably linked food and health to the point where it was the central organizing determinant guiding their food selection. They also felt the need to make informed dietary choices, but perceived their search for a healthy diet to be thwarted by the amount, type, and accuracy of information concerning the elements in today's food products. A constant search for accurate information and the instability of what participants consider expert advice contribute to feelings of anxiety around food choices and a sense of futility in their efforts to navigate through the information available. The focus group discussions reflected the emergence of an Orthorexic Society, whereby individuals are socialized to take charge of their own dietary health. They do so constrained by a food system that is increasingly complex, contradictory, and opaque and where commercial dietary regimes offer quick yet incomplete solutions. PMID- 21983048 TI - Can we cut out the meat of the dish? Constructing consumer-oriented pathways towards meat substitution. AB - The shift towards a more sustainable diet necessitates less reliance on foods of animal origin. This study presents data from a representative survey of Dutch consumers on their practices related to meat, meat substitution and meat reduction. The practices reflected a cultural gradient of meat substitution options running from other products of animal origin and conventional meat free meals to real vegetarian meals. To investigate feasible substitution options, a variety of meals without meat were presented using photos, which were rated by the participants in terms of attractiveness and chances that they would prepare a similar meal at home. The results demonstrated the influence of meal formats, product familiarity, cooking skills, preferences for plant-based foods and motivational orientations towards food. In particular, a lack of familiarity and skill hampered the preparation of real vegetarian meals. Based on the findings we propose a diversified understanding of meat substitution and we specify four policy-relevant pathways for a transition towards a more plant-based diet, including an incremental change towards more health-conscious vegetarian meals, a pathway that utilizes the trend towards convenience, a pathway of reduced portion size, and practice-oriented change towards vegetarian meals. PMID- 21983049 TI - Experimental effects of chocolate deprivation on cravings, mood, and consumption in high and low chocolate-cravers. AB - This study examined how deprivation of chocolate affects state-level chocolate cravings, mood, and chocolate consumption in high and low trait-level chocolate cravers. After identifying high and low chocolate cravers (N=58), half of the participants were instructed not to eat any chocolate for 2weeks. This created four experimental groups: deprived high-cravers (n=14), deprived low-cravers (n=14), non-deprived high-cravers (n=15), and non-deprived low-cravers (n=15). Following 2-week deprivation, state-level food cravings, mood, and chocolate intake were measured in a laboratory setting and compared across groups. Analyses revealed that anxiety increased over time for high-cravers (both deprived and non deprived); state-level chocolate- and food-craving increased over time for both deprived groups and non-deprived high-cravers; non-deprived high-cravers ate the most chocolate; and, high-cravers were more joyful and guilty than low-cravers after eating chocolate in the laboratory. Theoretically, these results suggest that chocolate consumption may be better explained by trait-level of chocolate craving than by deprivation and highlighted significant differences in mood, state-level cravings, and chocolate intake between cravers and non-cravers following deprivation. PMID- 21983050 TI - Using a novel computer-based approach to assess the acute effects of exercise on appetite-related measures. AB - Measuring food intake using standard buffet meals can be complicated by sensory and external cues which can alter energy intake. The present study was designed to examine the effects of acute exercise on non-metabolic factors related to appetite and food intake using a computer-based assessment. Twenty-seven men and women participated in two sessions in random order: 60-min walking on the treadmill (exercise trial; EX) or seated rest (control trial; CON). Subjective hunger and fullness, food liking, food utility, and ideal portion size were assessed before and immediately after exercise or rest, and hourly for 2 h. The findings showed that an acute bout of moderate intensity exercise had an anorexigenic effect; characterised by diminished hunger (-17.4%, p=0.004) and lower prospective ideal portion size (-7.7%, p=0.003) compared to no exercise. This novel, computer-based assessment, is a useful alternative to buffet meals setting and allows for the determination of non-metabolic factors associated with feeding behaviour in relation to exercise. PMID- 21983051 TI - Food cravings discriminate differentially between successful and unsuccessful dieters and non-dieters. Validation of the Food Cravings Questionnaires in German. AB - Food cravings have been strongly associated with triggering food consumption. However, definitions and measurements of food cravings are heterogeneous. Therefore, Cepeda-Benito and colleagues (2000) have suggested the Food Cravings Questionnaires (FCQs) to measure food cravings as a multidimensional construct at trait- and state-level. In the current study, we validated a German version of the FCQs in an online study (N=616). The factor structure of the state and trait versions could partially be replicated, but yielded fewer than the originally proposed factors. Internal consistencies of both versions were very good (Cronbach's alpha>.90), whereas retest reliability of the state version was expectedly lower than that of the trait version. Construct validity of the trait version (FCQ-T) was demonstrated by high correlations with related eating behavior questionnaires and low correlations with questionnaires unrelated to eating. Most importantly, FCQ-T-subscales were able to discriminate between successful and unsuccessful dieters and non-dieters. Validity of the state version was supported by positive relations with food deprivation and current negative affect. Taken together, the German version of the FCQs has good psychometric properties. Moreover, this study provided first evidence that distinct dimensions of food cravings are differentially related to success and failure in dieting. PMID- 21983052 TI - Willingness to pay for wholesome canteen takeaway. AB - The primary objective of this study was to estimate the willingness to pay (WTP) for a new intervention at the workplace: wholesome canteen takeaways (CTA), i.e. a low fat meal with a large amount of vegetables prepared at the workplace canteen that only requires re-heating. The contingent valuation method was used to elicit the WTP. Two surveys were carried out in Denmark; one large-scale Internet based survey and one survey at a workplace that introduced CTA. The results from the large-scale survey suggest that this concept attracts relevant target groups; groups of individuals with a less healthy diet, low physical activity and a high body mass index. For males and individuals with low education, who also constitute relevant target groups, the results suggest no significant difference in WTP between males and females, whereas low educated individuals have a significantly lower WTP than highly educated individuals. However, the workplace study, carried out at a hospital, found that females have a significantly higher WTP for CTA compared with males. In conclusion, the concept appears to attract relevant target groups, although for a given price a smaller fraction of low educated individuals compared to high educated individuals would be willing to buy CTA. PMID- 21983053 TI - Effects of meal frequency and snacking on food demand in mice. AB - Ad libitum feeding patterns in mice show substantial differences between laboratories, in addition to large individual and time-of-day differences. In the present study, we examine how mice work for food when access to food is temporally restricted and so they are forced to take discrete meals. In a first experiment, separate groups of ICR:CD1 mice were given access to food for 4, 8 or 16 opportunities or meals per day, with the duration of access at each opportunity adjusted reciprocally so that the total time of availability was 160 min per day in all three conditions. During the periods of availability, mice were able to earn food pellets by nose poke responses, according to an incrementing series of fixed unit prices (FUP: 2, 5, 10, 25) with each schedule in force for 3-4 days. Total food intake was similar in all three groups, indicating that mice generally were able to adjust their intake to a range of temporal availabilities. In each group, food demand fell as FUP increased. In the 8 and 16 meal groups, no food was eaten in many of the opportunities. Within an opportunity, the rate of intake generally declined with time, indicative of satiation. At low FUPs, later opportunities in each day were associated with smaller meals than earlier opportunities; in contrast, at high FUPs the first opportunity was also a small meal. Collectively, these results show that mice eat less at higher costs but not because of time constraints of the schedule: instead, they exhibit an elective anorexia. In the second experiment, we examined whether snacking between imposed meals would affect subsequent meal(s). Mice were adapted to the foregoing 8 opportunity protocol. Then, half the mice received free snacks of sugar cubes after the 3rd, 4th and 5th meal opportunities and the intakes of sugar and pellets were examined at low and high unit costs for pellets (FUP2 and 25). At FUP2, mice decreased demand for pellets and compensated energetically for the sugar they consumed. At FUP25, mice also decreased demand, but by less than the energy obtained from sugar. These data show that choice for pellets over a free palatable snack, and subsequent compensation of energy intake, is modified by effort and demand. PMID- 21983054 TI - Determinants and nutritional implications associated with low-fat food consumption. AB - OBJECTIVES: the objective was to study determinants and nutritional implications associated with low-fat food consumption. METHODS: a cross-sectional design was used, 5,000 military men were contacted and 1,852 participated. Using mailed questionnaires, the low-fat food consumption frequency was recorded and stratified in number of portions a day. The following low-fat food items were included: mayonnaise, yoghurt, milk, cheese, cottage cheese and meat. RESULTS: the two most daily consumed low-fat foods were meat and yoghurt by, respectively, 21.7% and 17.3% of the participants. Only 3.5% consumed a daily portion of low fat cheese, and 7.4% consumed one or more daily portions of low-fat milk. After adjustment, Body Mass Index (BMI), physical activity and non-smoking were associated with an increasing consumption of low-fat foods. Consumption of low fat foods was associated with a decreased daily total and saturated fat intake, from respectively, 37.9 and 14.7 energy-percent for low consumption to 30.5 and 11.6 energy-percent for high consumption. This decrease was compensated by an increased intake in carbohydrates and sugar, respectively, 42.5 and 16.7 energy percent to 46.5 and 22.6 energy-percent. CONCLUSIONS: age, BMI, physical activity and non-smoking were associated with an increasing consumption of low-fat foods. The fact that low-fat foods consumers had a higher intake of carbohydrates and proteins question the efficacy of these items in energy reducing programs. PMID- 21983055 TI - Comparative analysis of the safety and efficacy of transcatheter arterial chemoembolization and yttrium-90 radioembolization in patients with unresectable hepatocellular carcinoma. AB - PURPOSE: To compare retrospectively the safety and efficacy of yttrium-90 ((90)Y) radioembolization with the safety and efficacy of chemoembolization in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Survival and complication rates were evaluated for patients with HCC who underwent chemoembolization or radioembolization at a single institution between August 2007 and April 2010. Complications were graded according to a standardized grading system for embolization procedures. Survival was determined via the Kaplan-Meier method, and multivariable analysis for factors affecting survival was performed. RESULTS: This study included 73 patients with HCC who underwent index embolization with radioembolization (n = 38; 52.1%) or chemoembolization (n = 35; 47.9%). The two patient populations were similar in terms of demographics, etiology of cirrhosis, functional status, tumor characteristics, Child-Pugh class, previous liver-directed therapy, and number of patients with bilirubin > 2.0 mg/dL. There was no significant difference in survival between the radioembolization (median 8.0 months) and chemoembolization (median 10.3 months) cohorts (P = .33). Postembolization syndrome was significantly more severe in patients who underwent chemoembolization, which led to increased total hospitalization rates in these patients. The rates of other complications and rehospitalization were similar between groups. Increased age, Child-Pugh class B, hepatitis seropositivity, bilobar tumor distribution, tumor vascular invasion, and presence of extrahepatic metastases were associated with reduced patient survival. CONCLUSIONS: Patients treated with radioembolization did not show a survival advantage over patients treated with chemoembolization. However, patients who underwent chemoembolization had significantly higher rates of hospitalization as a result of postembolization syndrome. PMID- 21983056 TI - Percutaneous vertebroplasty for vertebral compression fractures with intravertebral cleft: cement injection under vacuum aspiration. AB - PURPOSE: To evaluate the efficacy of cement injection under vacuum aspiration (CIVAS) of cleft contents in percutaneous vertebroplasty for osteoporotic vertebral compression fractures with an intravertebral cleft. MATERIALS AND METHODS: From April 2008 to October 2010, vertebroplasty for single-level osteoporotic vertebral compression fractures with clefts was performed in 34 patients (seven women, 27 men; mean age, 77 y) with CIVAS and in 41 patients (three women, 38 men; mean age, 77 y) by conventional injection (control group). In this retrospective study, the cement volume, cement ratio, visual analog scale (VAS) pain score, and incidences of leakage, new vertebral compression fracture, and nonhealing were compared between groups. Vertebral height changes in the CIVAS group were also evaluated. RESULTS: There were significant decreases in VAS scores in both groups (P < .001). There were no significant differences in complications between groups (cement leakage, P = .70; new vertebral compression fracture, P = .17; nonhealing, P = .086). Vertebral height was significantly decreased by vacuum aspiration and increased by cement injection (P < .001). The mean cement volume was significantly higher (P = .0057) in the CIVAS group (4.87 mL) than in the control group (3.58 mL). Cement filling was achieved more sufficiently in the CIVAS group (P = .014). CONCLUSIONS: The CIVAS method is feasible and appears to improve cleft filling in the treatment of single-level vertebral compression fractures with a cleft, compared with conventional cement injection. PMID- 21983057 TI - Culture modulates brain activity during empathy with anger. AB - Interdependent cultures (such as the Chinese) and independent cultures (such as the German) differ in their attitude towards harmony that is more valued in interdependent cultures. Interdependent and independent cultures also differ in their appreciation of anger--an emotion that implies the disruption of harmony. The present study investigated if interdependent and independent cultures foster distinct brain activity associated with empathic processing of familiar angry, familiar neutral, and unfamiliar neutral faces. Using functional MRI, we scanned Chinese and German healthy subjects during an intentional empathy task, a control task (the evaluation of skin color), and a baseline condition. The subject groups were matched with regard to age, gender, and education. Behaviorally, Chinese subjects described themselves as significantly more interdependent compared to German subjects. The contrast 'intentional empathy for familiar angry'>'baseline' revealed several regions, including the left inferior frontal cortex, the left supplementary motor area, and the left insula, that showed comparable hemodynamic responses in both groups. However, the left dorsolateral prefrontal cortex had stronger hemodynamic responses in Chinese subjects in the contrast 'intentional empathy for familiar angry'>'baseline'. Germans, in contrast, showed stronger hemodynamic responses in the right temporo-parietal junction, right inferior and superior temporal gyrus, and left middle insula for the same contrast. Hemodynamic responses in the latter three brain regions correlated with interdependences scores over all subjects. Our results suggest that enhanced emotion regulation during empathy with anger in the interdependent lifestyle is mediated by the left dorsolateral prefrontal cortex. Increased tolerance towards the expression of anger in the independent lifestyle, in contrast, is associated with increased activity of the right inferior and superior temporal gyrus and the left middle insula. PMID- 21983058 TI - [Extremely prolonged neuromuscular block after a single dose of rocuronium]. AB - Postoperative curarization in patients has been established. Nevertheless, extremely prolonged neuromuscular blockades are rare. We report the case of a prolonged neuromuscular blockade (lasting 10 hours) following a single dose of rocuronium, in an elderly patient with severe renal failure. We have studied the possible causes of prolonged curarization, and discussed the interest of the use of sugammadex in such cases. PMID- 21983059 TI - Topical treatment of CHILD nevus and Sjogren-Larsson Syndrome with combined lovastatin and cholesterol. PMID- 21983060 TI - Vegetarian diets and incidence of diabetes in the Adventist Health Study-2. AB - AIM: To evaluate the relationship of diet to incident diabetes among non-Black and Black participants in the Adventist Health Study-2. METHODS AND RESULTS: Participants were 15,200 men and 26,187 women (17.3% Blacks) across the U.S. and Canada who were free of diabetes and who provided demographic, anthropometric, lifestyle and dietary data. Participants were grouped as vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian (reference group). A follow-up questionnaire after two years elicited information on the development of diabetes. Cases of diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semi-vegetarians and 2.12% of non-vegetarians. Blacks had an increased risk compared to non-Blacks (odds ratio [OR] 1.364; 95% confidence interval [CI], 1.093-1.702). In multiple logistic regression analysis controlling for age, gender, education, income, television watching, physical activity, sleep, alcohol use, smoking and BMI, vegans (OR 0.381; 95% CI 0.236-0.617), lacto ovo vegetarians (OR 0.618; 95% CI 0.503-0.760) and semi-vegetarians (OR 0.486, 95% CI 0.312-0.755) had a lower risk of diabetes than non-vegetarians. In non-Blacks vegan, lacto ovo and semi vegetarian diets were protective against diabetes (OR 0.429, 95% CI 0.249-0.740; OR 0.684, 95% CI 0.542-0.862; OR 0.501, 95% CI 0.303-0.827); among Blacks vegan and lacto ovo vegetarian diets were protective (OR 0.304, 95% CI 0.110-0.842; OR 0.472, 95% CI 0.270-0.825). These associations were strengthened when BMI was removed from the analyses. CONCLUSION: Vegetarian diets (vegan, lacto ovo, semi-) were associated with a substantial and independent reduction in diabetes incidence. In Blacks the dimension of the protection associated with vegetarian diets was as great as the excess risk associated with Black ethnicity. PMID- 21983061 TI - Quantum Hall effect in kagome lattices under staggered magnetic field. AB - The interplay of staggered magnetic field (SMF) and uniform magnetic field (UMF) on the quantum Hall effect (QHE) in kagome lattices is investigated in the weak UMF limit. The topological band gaps coming from SMF are robust against UMF although the extended bands split into a series of Landau levels. With SMF applied, in the unconventional QHE region, one plateau of Hall conductance becomes wider and the others are compressed. Meanwhile, one of the two series of integer Hall plateaus splits and the resulting two series of Hall plateaus still exhibit the integer behavior. The Hall conductance varies with SMF step by step with the step height being e(2)/h or 2e(2)/h according to the QHE being conventional or unconventional. In the transitional regions, redistribution of Chern numbers happens even in the weak UMF limit. PMID- 21983062 TI - Built environment, physical activity, and obesity: what have we learned from reviewing the literature? AB - To evaluate the growing literature on the built environment and physical activity/obesity, we conducted a review of review papers. Through a systematic search, we identified 36 reviews that met the inclusion criteria and evaluated these reviews based on key information provided, review methodology, and specificity regarding measurement. We also analyzed research gaps and areas of improvement identified by previous reviews and propose a research agenda. Future studies should develop complex conceptual and statistical models that include moderators and mediators, improve objective and perceived measures of the built environment, and strengthen evidence of causality through better research designs. PMID- 21983063 TI - Intestinal dysbiosis in inflammatory bowel disease. AB - The worldwide incidence of inflammatory bowel disease (IBD) is increasing. Abundant literature has suggested that an imbalance between harmful and protective bacteria, or dysbiosis, of the intestine is largely responsible for the rising incidence of IBD. In this review, data supporting dysbiosis as a cause of IBD are presented. A comparison of the number of scientific publications in the US versus Europe on intestinal dysbiosis and microbiota revealed the US scientific community has a lower level of interest in studying dysbiosis and microbiota compared the research community in Europe. The rising trend of antibiotic use in the US provides further evidence of the lack of concern for the effect of dysbiosis on human health. Further research to understand the causal relationship between dysbiosis and IBD are needed to better guide clinical practice in using probiotics. PMID- 21983064 TI - Waking the wimp: redox-modulation activates human beta-defensin 1. PMID- 21983065 TI - Bacteriophages: the ultimate agents of change. PMID- 21983066 TI - Further characterization of Shigella sonnei live vaccine candidates WRSs2 and WRSs3-plasmid composition, invasion assays and Sereny reactions. PMID- 21983067 TI - Influence of mother's intestinal microbiota on gut colonization in the infant. AB - The aim here was to elucidate the mother-infant association in the gut colonization of 1-6 month-old infants and to establish whether probiotics can influence this process. Fecal samples from 80 mother-infant pairs were analyzed at 1 month (mothers and infants) and 6 months (infants) by real-time polymerase chain reaction to assess bacterial numbers. This double-blind placebo-controlled trial involved 2 different probiotic combinations (1. Lactobacillus rhamnosus + Bifidobacterium longum and 2. Lactobacillus paracasei + Bifidobacterium longum) given to the mothers 2 months prior to and 2 months after delivery. Bifidobacterium bifidum colonization in the mothers significantly increased the infants' probability of being colonized by B. bifidum and their bifidobacterial diversity indexes (DI) and the mother-infant similarity indexes (SI) both at 1 and 6 months of age. The counts of Bifidobacterium genus (at 1 month) and Bifidobacterium longum (at 6 months) correlated between mothers and infants. At 6 months, a significant effect of the probiotic intervention was found in the mother-infant association of fecal bifidobacterial counts but not in the colonization frequencies, DI or SI. In conclusion, a clear association between mother and infant was found in gut colonization by bifidobacteria. Maternal colonization by B. bifidum had the most consistent effects on the infant's bifidobacterial microbiota. Maternal probiotic treatment had little effect on this mother-infant association. PMID- 21983068 TI - The fecal bifidobacterial transcriptome of adults: a microarray approach. AB - Bifidobacteria are a predominant group present among adult human intestinal microbiota and are considered to be beneficial to host health. Both the dynamics and functional activity of bifidobacteria from the intestinal tract of four adults, following ingestion of a mix consisting of short chain galactooligosaccharides, long chain fructooligosaccharides and acidic oligosaccharides from pectin hydrolysate (GFP), was investigated. The percentage of total bifidobacteria, monitored by quantitative real time PCR, was not significantly altered but marked species-specific changes occurred in all individuals over time, indicating a dynamic bifidobacterial community. Insight into the functional activity of the bifidobacteria was acquired using a clone library-based microarray comprising the genomes of various bifidobacteria to reveal the bifidobacterial transcriptome within the fecal community. Total RNA from the fecal microbial community was hybridized to the microarray and 310 clones were selected for sequencing which revealed genes belonging to a wide range of functional groups demonstrating substantial metabolic activity. While the intake of GFP did not have a significant effect on the overall change in gene expression, 82 genes showed a significant change. Most of the predicted genes were involved in metabolism of carbohydrates of plant origin, house keeping functions such as DNA replication and transcription, followed by membrane transport of a wide variety of substrates including sugars and metals and amino acid metabolism. Other genes were involved in transport, nucleotide metabolism, amino acid metabolism, environmental information processing and cellular processes and signalling. A smaller number of genes were involved in general metabolism, glycan metabolism, energy metabolism, lipid metabolism and cell surface. These results support the notion that bifidobacteria utilize mainly indigestible polysaccharides as their main source of energy and biosynthesis of cellular components. PMID- 21983069 TI - Acute necrotizing enterocolitis of preterm piglets is characterized by dysbiosis of ileal mucosa-associated bacteria. AB - Investigation of bacteria involved in pathogenesis of necrotizing enterocolitis (NEC) is limited by infant fragility, analysis restricted to feces, use of culture-based methods, and lack of clinically-relevant animal models. This study used a unique preterm piglet model to characterize spontaneous differences in microbiome composition of NEC-predisposed regions of gut. Preterm piglets (n=23) were cesarean-delivered and nurtured for 30 hours over which time 52% developed NEC. Bacterial DNA from ileal content, ileal mucosa, and colonic mucosa were PCR amplified, subjected to terminal restriction fragment length polymorphism (TRFLP) analysis and targeted 16S rDNA qPCR. Preterm ileal mucosa was specifically bereft in diversity of bacteria compared to ileal content and colonic mucosa. Preterm ileum was restricted to representation by only Proteobacteria, Firmicutes, Cyanobacteria and Chloroflexi. In piglets with NEC, ileal mucosa was uniquely characterized by increases in number of Firmicutes and diversity of phyla to include Actinobacteria and uncultured bacteria. Five specific TRFLP profiles, corresponding in closest identity to Clostridium butyricum, C. neonatale, C. proteolyticum, Streptomyces spp., and Leptolyngbya spp., were significantly more prevalent or observed only among samples from piglets with NEC. Total numbers of Clostridium spp. and C. butyricum were significantly greater in samples of NEC ileal mucosa but not ileal content or colonic mucosa. These results provide strong support for ileal mucosa as a focus for investigation of specific dysbiosis associated with NEC and suggest a significant role for Clostridium spp., and members of the Actinobacteria and Cyanobacteria in the pathogenesis of NEC in preterm piglets. PMID- 21983070 TI - Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers. PMID- 21983071 TI - Relaxin regulates myofibroblast contractility and protects against lung fibrosis. AB - Myofibroblasts are specialized contractile cells that participate in tissue fibrosis and remodeling, including idiopathic pulmonary fibrosis (IPF). Mechanotransduction, a process by which mechanical stimuli are converted into biochemical signals, regulates myofibroblast differentiation. Relaxin is a peptide hormone that mediates antifibrotic effects through regulation of collagen synthesis and turnover. In this study, we demonstrate enhanced myofibroblast contraction in bleomycin-induced lung fibrosis in mice and in fibroblastic foci of human subjects with IPF, using phosphorylation of the regulatory myosin light chain (MLC(20)) as a biomarker of in vivo cellular contractility. Compared with wild-type mice, relaxin knockout mice express higher lung levels of phospho MLC(20) and develop more severe bleomycin-induced lung fibrosis. Exogenous relaxin inhibits MLC(20) phosphorylation and bleomycin-induced lung fibrosis in both relaxin knockout and wild-type mice. Ex vivo studies of IPF lung myofibroblasts demonstrate decreases in MLC(20) phosphorylation and reduced contractility in response to relaxin. Characterization of the signaling pathway reveals that relaxin regulates MLC(20) dephosphorylation and lung myofibroblast contraction by inactivating RhoA/Rho-associated protein kinase through a nitric oxide/cGMP/protein kinase G-dependent mechanism. These studies identify a novel antifibrotic role of relaxin involving the inhibition of the contractile phenotype of lung myofibroblasts and suggest that targeting myofibroblast contractility with relaxin-like peptides may be of therapeutic benefit in the treatment of fibrotic lung disease. PMID- 21983072 TI - GGPPS, a new EGR-1 target gene, reactivates ERK 1/2 signaling through increasing Ras prenylation. AB - Cigarette smoke activates the extracellular signal-regulated kinase (ERK) 1/2 mitogen activated-protein kinase pathway, which, in turn, is responsible for early growth response gene-1 (EGR-1) activation. Here we provide evidence that EGR-1 activation can also reactivate ERK 1/2 mitogen activated-protein kinase through a positive feedback loop through its target gene (geranylgeranyl diphosphate synthase) GGPPS. For the first time, the GGPPS gene is identified as a target of EGR-1, as EGR-1 can directly bind to the predicted consensus-binding site in the GGPPS promoter and regulate its transcription. Long-term observations show that there are two ERK 1/2 phosphorylation peaks after cigarette smoke extract stimulation in human lung epithelial Beas-2B cells. The first peak (at 10 minutes) is responsible for EGR-1 accumulation, and the second (at 4 hours) is diminished after the disruption of EGR-1 transcriptional activity. EGR-1 overexpression enhances Ras prenylation and membrane association in a GGPPS dependent manner, and it augments ERK 1/2 activation. Likewise, a great reduction of the second peak of ERK 1/2 phosphorylation is observed during long-term cigarette smoke extract stimulation in cells where GGPPS is disrupted. Thus, we have uncovered an intricate positive feedback loop in which ERK 1/2-activated EGR 1 promotes ERK 1/2 reactivation through promoting GGPPS transcription, which might affect cigarette smoke-related lung pathological processes. PMID- 21983073 TI - Phosphodiesterase-5 inhibition prevents postcardiopulmonary bypass acute kidney injury in swine. AB - BACKGROUND: Acute kidney injury after cardiac surgery is common, has no effective treatments, and is associated with adverse outcomes. The aim of this study was to determine whether administration of the phosphodiesterase-5 inhibitor sildenafil citrate (SDF) would prevent the development of post-cardiopulmonary bypass (CPB) acute kidney injury in swine. METHODS: Adult pigs (n = 8 per group) were randomized to undergo sham procedure, CPB, or CPB plus administration of SDF, with recovery and reassessment at 24 hours. RESULTS: Cardiopulmonary bypass resulted in a significant reduction in creatinine clearance relative to sham pigs (mean difference CPB versus sham, -47.9 mL/min; 95% confidence interval [CI]: 93.7 to -2.2; p = 0.039). This was prevented by the administration of SDF during CPB (mean difference CPB+SDF versus CPB, +55.6 mL/min; 95% CI: +6.5 to +104.7; p = 0.024). Cardiopulmonary bypass also resulted in a significant rise in the urinary biomarker interleukin-18 compared with sham procedures (mean difference 209.3 pg/mL; 95% CI: 120.6 to 298.1; p < 0.001) that was prevented by SDF administration. Post-CPB kidney injury was associated with vascular endothelial injury and dysfunction, reduced nitric oxide bioavailability, medullary hypoxia, cortical adenosine triphosphate depletion, inflammation, and evidence of proximal tubule epithelial cell stress manifest as phenotypic change. Administration of SDF to CPB pigs preserved nitric oxide bioavailability and prevented endothelial dysfunction, regional hypoxia, inflammation, and tubular changes. CONCLUSIONS: In this model, phosphodiesterase-5 inhibition using SDF prevented post-CPB acute kidney injury by the preservation of nitric oxide bioavailability, and warrants evaluation as a renoprotective agent in clinical trials. PMID- 21983074 TI - Reoperation after the Ross procedure: incidence, management, and survival. AB - BACKGROUND: The risk of reoperation on the autograft and homograft is the major long-term drawback of the Ross procedure. The incidence and clinical implications of reoperations after the Ross procedure are reported. METHODS: Between March 1992 and February 2010, 336 consecutive patients had a Ross procedure (mean follow-up, 6.2+/-4.9 years). Autograft implant technique was freestanding root replacement in 269 patients, subcoronary implantation in 52 patients and a modified root replacement with the autograft included in a Valsalva tube graft in 15. RESULTS: Subsequently, 38 patients (11.3%) underwent reoperations, for autograft dilatation in 23 and a significant autograft insufficiency in 9, at 9.6+/-3.7 years and 2.6+/-3.9 years, respectively. Aortic and pulmonary infective endocarditis occurred in 3 patients. Three patients underwent a non valve-related cardiac reoperation. Three patients received a transcatheter pulmonary valve implantation after 12.2+/-1.7 years. At 15 years, freedoms for autograft and homograft explantation (with 95% confidence interval) were 83.3% (77.4%- to 9.2%) and 92.8% (87.6% to 97.9%), respectively. Native aortic valve regurgitation, indexed aortic annulus diameter exceeding 1.35 cm/m2 and autograft diameter were risk factors for dilated autograft reoperation (hazard ratio, 3.23 [95% confidence interval, 1.19 to 8.81], p=0.02; 3.83 [0.9 to 16.33], p=0.07 and 1.2 per mm [1.01 to 1.41], p=0.03), respectively. CONCLUSIONS: Autograft dilatation was the leading cause of reoperation in patients who underwent root replacement. Long-term follow-up is mandatory to determine whether modifications of the operative technique could limit autograft dilatation. PMID- 21983075 TI - Drosophila spoonbill encodes a dual-specificity A-kinase anchor protein essential for oogenesis. AB - spoonbill is a Drosophila female-sterile mutation, which interferes with normal egg patterning during oogenesis. Previous analyzes linked the mutation to a number of seemingly unrelated pathways, including GRK/EGFR and DPP, two major pathways essential for Drosophila and vertebrate development. Further work suggested that spoonbill may also function in actin polymerization and border cell migration. Here we describe the molecular cloning of the spoonbill gene and characterize new mutant alleles, further demonstrating that spoonbill's function is essential during oogenesis. We found spoonbill to be allelic to CG3249 (also known as yu), which encodes the only known dual-specificity A-kinase anchor protein in Drosophila. Our data indicate that similar to mammalian AKAPs, Spoonbill protein contains a number of potential kinase and phosphatase binding motifs, and is targeted, in the ovary, to mitochondria and Golgi. Finally, we address some of spoonbill's mutant phenotypes from the perspective of the published data on the AKAP protein family. PMID- 21983076 TI - Biphasic stress response in the soleus during reloading after hind limb unloading. AB - INTRODUCTION: Extreme disuse and spaceflight elicit rapid skeletal muscle atrophy, accompanied by elevated proinflammatory signaling and impaired stress response proteins (e.g., heat shock proteins (HSP), insulin-like growth factor 1 (IGF-1)). Recovery of muscle mass is delayed during the early stage of reloading after prolonged unloading, with a concomitant impairment of HSP70 and IGF-1. We postulated that proinflammatory signaling and stress response alterations would characterize early and late phases of signaling during reloading. METHODS: Twenty four adult SD rats were divided into the following groups: controls, 28 d of hind limb unloading (HU), HU + early (7 d) reloading (HU-R7), and HU + late (28 d) reloading (HU-R28). RESULTS: Soleus mass decreased (-55%) with HU and remained depressed (-41%) at HU-R7. Nuclear factor kappaB activation and oxidative stress were elevated with HU and remained high during reloading. HU elevated inducible nitric oxide synthase and returned to baseline during reloading, whereas 3 nitrotyrosine did not increase with HU and peaked at HU-R7. HU depressed levels of HSP25 phosphorylation at Ser82 and IGF-1. Although p-HSP25 and Akt phosphorylation (Ser473) recovered during early reloading, HSP70, heat shock factor 1, and IGF-1 remained depressed. HSP70, heat shock factor 1, and IGF-1 recovered, whereas p-Akt and 3-nitrotyrosine decreased to control levels at HU R28. CONCLUSIONS: Reloading elicited an early phase characterized by elevated nuclear factor kappaB activation, 3-nitrotyrosine, p-HSP25, and p-Akt levels and a delayed phase with recovery of HSP70, IGF-1, and muscle mass. We conclude that the reloading phenotype in skeletal muscle is expressed in two distinct phases related to (a) pro-inflammatory signaling and (b) muscle mass recovery. PMID- 21983077 TI - Validity, practical utility, and reliability of the activPALTM in preschool children. AB - PURPOSE: With the increasing global prevalence of childhood obesity, it is important to have appropriate measurement tools for investigating factors (e.g., sedentary time) contributing to positive energy balance in early childhood. For preschool children, single-unit monitors such as the activPALTM are promising. However, validation is required because activity patterns differ from adults. METHODS: Thirty preschool children participated in a validation study. Children undertaking usual nursery activity while wearing an activPALTM 1 h were recorded using a video camera. Video (criterion method) was analyzed on a second-by-second basis to categorize posture and activity. This was compared with the corresponding activPALTM output. In a subsequent substudy investigating practical utility and reliability, 20 children wore an activPALTM for seven consecutive 24 h periods. RESULTS: A total of 97,750 s of direct observation from 30 children were categorized as sit/lie (46%), stand (35%), and walk (16%); with 3% of time in non-sit/lie/upright postures (e.g., crawl/crouch/kneel-up). Sensitivity for the overall total time-matched seconds detected as activPALTM "sit/lie" was 86.7%, specificity was 97.1%, and positive predictive value was 96.3%. For individual children, the median (interquartile range) sensitivity for activPALTM sit/lie was 92.8% (76.1%-97.4%), specificity was 97.3% (94.9%-99.2%), and positive predictive value was 97.0% (91.5%-99.1%). The activPALTM underestimated total time spent sitting (mean difference = -4.4%, P < 0.01) and overestimated time standing (mean difference = 7.1%, P < 0.01). There was no difference in overall percent time categorized as "walk" (P = 0.2). The monitors were well tolerated by children during a 7-d period of free-living activity. In the reliability study, at least 5 d of monitoring was required to obtain an intraclass correlation coefficient of >= 0.8 for time spent "sit/lie" according to activPALTM output. CONCLUSIONS: The activPALTM had acceptable validity, practical utility, and reliability for the measurement of posture and activity during free-living activities in preschool children. PMID- 21983079 TI - Physico-chemical parameters that govern nanoparticles fate also dictate rules for their molecular evolution. AB - Nanoparticles are efficient to safely deliver therapeutic and imaging contrast agents to tumors for cancer diagnostic and therapy, if they can escape the reticuloendothelial system (RES) and accumulate in tumors either passively due to the enhanced permeability and retention (EPR) effect or actively via a specific ligand. The main hallmark of nanoparticles is their large surface areas, which, depending of their chemical compositions, surface coatings, electric charges, sizes and shapes, will generate complex, extremely dynamic and continuous interactions and exchanges between the nanoparticles and the different molecules present in the blood. Special attention will be paid to explain how the nanoparticles were improved step by step in order to adapt our increasing knowledge on their biophysics. In particular, we will discuss the influence of PEGylation, the difficulties to generate actively targeted particles and finally the actual trends in the manufacturing of "third-generation" smart particles. PMID- 21983078 TI - Transepithelial transport and toxicity of PAMAM dendrimers: implications for oral drug delivery. AB - This article summarizes efforts to evaluate poly(amido amine) (PAMAM) dendrimers as carriers for oral drug delivery. Specifically, the effect of PAMAM generation, surface charge and surface modification on toxicity, cellular uptake and transepithelial transport is discussed. Studies on Caco-2 monolayers, as models of intestinal epithelial barrier, show that by engineering surface chemistry of PAMAM dendrimers, it is possible to minimize toxicity while maximizing transepithelial transport. It has been demonstrated that PAMAM dendrimers are transported by a combination of paracellular and transcellular routes. Depending on surface chemistry, PAMAM dendrimers can open the tight junctions of epithelial barriers. This tight junction opening is in part mediated by internalization of the dendrimers. Transcellular transport of PAMAM dendrimers is mediated by a variety of endocytic mechanisms. Attachment or complexation of cytotoxic agents to PAMAM dendrimers enhances the transport of such drugs across epithelial barriers. A remaining challenge is the design and development of linker chemistries that are stable in the gastrointestinal tract (GIT) and the blood stream, but amenable to cleavage at the target site of action. Recent efforts have focused on the use of PAMAM dendrimers as penetration enhancers. Detailed in vivo oral bioavailability of PAMAM dendrimer-drug conjugates, as a function of physicochemical properties will further need to be assessed. PMID- 21983080 TI - B cells that produce immunoglobulin E mediate colitis in BALB/c mice. AB - BACKGROUND & AIMS: Induction of colitis in mice by administration of oxazolone is mediated by T-helper (Th) 2 cells and has features of human ulcerative colitis. We investigated whether activation of interleukin (IL)-4Ralpha on T and B cells determines their effector functions and mediates oxazolone-induced colitis. METHODS: We studied induction of colitis with oxazolone in wild-type mice and those with CD4(+) T cells that did not express IL-4Ralpha (Lck(cre)IL-4Ralpha( /lox)). We also generated mice with B cells that did not express IL-4Ralpha (mb1(cre)IL-4Ralpha(-/lox)) and studied induction of colitis. RESULTS: Lck(cre)IL 4Ralpha(-/lox) mice did not develop colitis in response to oxazolone, and their levels of IL-4, IL-13, and immunoglobulin (Ig) E were reduced. Adoptive transfer of naive, wild-type CD4(+) Th cells depleted of natural killer T cells to Lck(cre)IL-4Ralpha(-/lox) mice restored their susceptibility to colitis. In contrast, Lck(cre)IL-4Ralpha(-/lox) mice maintained their protection against colitis when IL-13-deficient CD4(+) T cells were transferred. These findings indicate that development of colitis involves not only natural killer T-cell functions, but also requires IL-13 production by CD4(+) T helper cells. Mb1(cre)IL-4Ralpha(-/lox) mice, which cannot produce IgE, were also protected against oxazolone-induced colitis. Blocking IgE binding significantly reduced mast cell numbers in colons and protected wild-type BALB/c mice from the onset of colitis. CONCLUSIONS: IL-4 appears to induce CD4(+) Th2 cells to produce IL-13 and B cells to produce IgE, which together mediate oxazolone-induced colitis in mice. PMID- 21983081 TI - Helminth infection does not reduce risk for chronic inflammatory disease in a population-based cohort study. AB - BACKGROUND & AIMS: Parasitic helminth infections can suppress symptoms of allergy, type 1 diabetes, arthritis, and inflammatory bowel disease in animal models. We analyzed data from a large, population-based cohort study to determine whether common childhood enterobiasis protects against these diseases. METHODS: We collected information on individual prescriptions filled for the drug mebendazole against Enterobius vermicularis for all children born in Denmark 1995 2008 from the National Register of Medicinal Product Statistics (n = 924,749; age 0-14 years); 132,383 of these children (14%) filled a prescription for mebendazole, 102,482 of the children (11%) had a household peer who was registered with a filled mebendazole prescription, and the remaining 689,884 children (75%) comprised the reference group. Children diagnosed with asthma, type 1 diabetes, juvenile arthritis, ulcerative colitis, or Crohn's disease were identified from the National Patient Registry. We used Poisson regression to estimate confounder-adjusted incidence rate ratios for first in- or outpatient hospital diagnosis of chronic inflammatory disease according to history of mebendazole treatment prescribed to children in the study. RESULTS: Chronic inflammatory disease was diagnosed in 10,352 children during 6.4 million person years of follow-up. The incidence rate ratios was 1.07 for asthma (95% confidence interval [CI]: 1.00-1.13), 1.05 for type 1 diabetes (95% CI: 0.79-1.12), 1.13 for juvenile arthritis (95% CI: 0.94-1.37), 0.77 for ulcerative colitis (95% CI: 0.41 1.46), and 1.44 for Crohn's disease (95% CI: 0.82-2.53). Results were not modified by number of treatments or age at treatment. CONCLUSIONS: Based on a population-based analysis, enterobiasis does not reduce risk for asthma, type 1 diabetes, arthritis, or inflammatory bowel disease. PMID- 21983083 TI - Distinct association of the nuclear pore protein Nup153 with A- and B-type lamins. AB - The nuclear envelope (NE) is a double membrane physical barrier, which separates the nucleus from the cytoplasm. Underlying the NE are the nuclear lamins, which in combination with inner nuclear membrane proteins form the lamina. The lamina is crucial for maintaining the structural integrity of the nucleus and for positioning of nuclear pore complexes (NPCs) within the NE. The nucleoporin Nup153 has previously been reported to bind to B-type lamins. However, the specificity of this interaction is not well established. Here we show that Nup153 exhibits multiple binding sites for A- and B-type lamins. Using GST-pull down assays, we found that both the N-terminal domain of Nup153 and its C terminus associate with the Ig-fold domain of A- and B-type lamins. By employing purified Nup153 and lamin proteins in blot overlay assays we revealed that both the N terminal and the C-terminal domain of Nup153 are directly interacting with the lamins. Moreover, we provide evidence that mutations in the lamin A Ig-fold domain selectively affect Nup153-binding, suggesting that Nup153 may play a role in lamin-associated diseases, known as laminopathies. Together our results indicate a far more intricate interplay between Nup153 and nuclear lamins than previously accepted. PMID- 21983082 TI - Reduced expression of UGT1A1 in intestines of humanized UGT1 mice via inactivation of NF-kappaB leads to hyperbilirubinemia. AB - BACKGROUND & AIMS: Bilirubin is a natural and potent antioxidant that accumulates in the blood of newborn children and leads to physiological jaundice. Breastfed infants have higher serum levels of bilirubin than formula-fed infants and are at risk for bilirubin-induced neurological dysfunction (BIND). Clearance of bilirubin requires the expression of uridine diphosphate glucuronosyltransferase (UGT) 1A1; we investigated its role in the association between breast feeding with jaundice in mice. METHODS: We studied mice in which the original Ugt1 locus was disrupted and replaced with the human UGT1 locus (hUGT1 mice); these mice spontaneously develop neonatal hyperbilirubinemia and BIND. We fed human breast milk or formula to neonatal hUGT1 mice and examined activation of the intestinal xenobiotic receptors pregnane X receptor and constitutive androstane receptor. We also examined inflammatory signaling pathways in mice with disruptions in IkappaB kinase-alpha and IkappaB kinase-beta in the intestinal epithelium. RESULTS: hUGT1 mice that were fed breast milk developed severe hyperbilirubinemia because of suppression of UGT1A1 in the gastrointestinal tract. Formula-fed hUGT1 mice had lower serum levels of bilirubin, which resulted from induction of UGT1A1 in the gastrointestinal tract. hUGT1/Pxr-null mice did not develop severe hyperbilirubinemia, whereas hUGT1/Car-null mice were susceptible to BIND when they were fed breast milk. Breast milk appeared to suppress intestinal IkappaB kinase alpha and beta, resulting in inactivation of nuclear factor-kappaB and loss of expression of UGT1A1, leading to hyperbilirubinemia. CONCLUSIONS: Breast milk reduces expression of intestinal UGT1A1, which leads to hyperbilirubinemia and BIND; suppression of this gene appears to involve inactivation of nuclear factor-kappaB. Hyperbilirubinemia can be reduced by activation of pregnane X receptor, constitutive androstane receptor, or nuclear factor-kappaB. PMID- 21983084 TI - Epigenetic control of DNA replication dynamics in mammals. AB - Every time a cell divides it must ensure that its genetic information is accurately duplicated and dis-tributed equally to the two daughter cells. This fundamental biological process is conserved through-out all kingdoms of life and relies on the correct and complete duplication of the DNA before a cell can divide and give rise to other cells or to multicellular organisms. Any mistakes in this process can result in genetic mutations or karyotype aberrations, which may lead to disease or even death. Whereas in prokaryotes the entire genome is replicated from a single origin, the increased genome size and complexity in mammals requires the spatio-temporal coordination of thousands of replica-tion origins. Furthermore, this spatio-temporal order of genome replication changes throughout de-velopment and cellular differentiation. Here we present and discuss current knowledge on the con-trol of DNA replication dynamics in mammals and the role of chromatin modifications in this basic biological process. PMID- 21983085 TI - Roles of chromatin insulator proteins in higher-order chromatin organization and transcription regulation. AB - Eukaryotic chromosomes are condensed into several hierarchical levels of complexity: DNA is wrapped around core histones to form nucleosomes, nucleosomes form a higher-order structure called chromatin, and chromatin is subsequently compartmentalized in part by the combination of multiple specific or unspecific long-range contacts. The conformation of chromatin at these three levels greatly influences DNA metabolism and transcription. One class of chromatin regulatory proteins called insulator factors may organize chromatin both locally, by setting up barriers between heterochromatin and euchromatin, and globally by establishing platforms for long-range interactions. Here, we review recent data revealing a global role of insulator proteins in the regulation of transcription through the formation of clusters of long-range interactions that impact different levels of chromatin organization. PMID- 21983086 TI - Evidence for a mammalian late-G1 phase inhibitor of replication licensing distinct from geminin or Cdk activity. AB - Pre-replication complexes (pre-RCs) are assembled onto DNA during late mitosis and G1 to license replication origins for use in S phase. In order to prevent re replication of DNA, licensing must be completely shutdown prior to entry into S phase. While mechanisms preventing re-replication during S phase and mitosis have been elucidated, the means by which cells first prevent licensing during late G1 phase are poorly understood. We have employed a hybrid mammalian / Xenopus egg extract replication system to dissect activities that inhibit replication licensing at different stages of the cell cycle in Chinese Hamster Ovary (CHO) cells. We find that soluble extracts from mitotic cells inhibit licensing through a combination of geminin and Cdk activities, while extracts from S-phase cells inhibit licensing predominantly through geminin alone. Surprisingly however, geminin did not accumulate until after cells enter S phase. Unlike extracts from cells in early G1 phase, extracts from late G1 phase and early S phase cells contained an inhibitor of licensing that could not be accounted for by either geminin or Cdk. Moreover, inhibiting cyclin and geminin protein synthesis or inhibiting Cdk activity early in G1 phase did not prevent the appearance of inhibitory activity. These results suggest that a soluble inhibitor of replication licensing appears prior to entry into S phase that is distinct from either geminin or Cdk activity. Our hybrid system should permit the identification of this and other novel cell cycle regulatory activities. PMID- 21983088 TI - Coding RNAs with a non-coding function: maintenance of open chromatin structure. AB - The multi-layered organization of the genome in a large nucleoprotein complex termed chromatin regulates nuclear functions by establishing subcompartments with distinct DNA-associated activities. Here, we demonstrate that RNA plays an important role in maintaining a decondensed and biologically active interphase chromatin conformation in human and mouse cell lines. As shown by RNase A microinjection and fluorescence microscopy imaging, digestion of single-stranded RNAs induced a distinct micrometer scale chromatin aggregation of these decondensed regions. In contrast, pericentric heterochromatin was more resistant to RNase A treatment. We identified a class of coding RNA transcripts that are responsible for this activity, and thus termed these 'chromatin-interlinking' RNAs or ciRNAs. The initial chromatin distribution could be restored after RNase A treatment with a purified nuclear RNA fraction that was analyzed by high throughput sequencing. It comprised long > 500 nucleotides (nt) RNA polymerase II (RNAP II) transcripts that were spliced, depleted of polyadenylation and was enriched with long 3'-untranslated regions (3'-UTRs) above ~800 nt in length. Furthermore, similar reversible changes of the chromatin conformation and the RNAP II distribution were induced by either RNA depletion or RNAP II inhibition. Based on these results we propose that ciRNAs could act as genome organizing architectural factors of actively transcribed chromatin compartments. PMID- 21983087 TI - The role of Lamin A in cytoskeleton organization in colorectal cancer cells: a proteomic investigation. AB - Up-regulated expression of lamin A has been implicated in increased cell invasiveness and mortality in colorectal cancer. Here we use quantitative proteomics to investigate lamin A regulated changes in the cytoskeleton that might underpin increased cell motility. Using siRNA knockdown of lamin A in a model cell line (SW480/lamA) we confirm that the presence of lamin A promotes cell motility. Using an enhanced technique to prepare cytoskeleton fractions in combination with 2D DiGE we were able to accurately and reproducibly detect changes in the representation of protein species within the cytoskeleton as low as 20%. In total 64 protein spots displayed either increased or decreased representation within the cytoskeleton of SW480/lamA cells compared to controls. Of these the identities of 29 spots were determined by mass spectrometry. A majority were multiple forms of three classes of proteins, including components of the actin and IF cytoskeletons, protein chaperones and translation initiation and elongation factors. In particular our data reveal that the representation of tissue transglutaminase 2, which is known to modify elements of the cytoskeleton and is associated with cancer progression, was highly over-represented in the cytoskeleton fraction of SW480/lamA cells. Overall, our data are consistent with changed protein cross-linking and folding that favours the formation of dynamic actin filaments over stress fibres accounting for the altered cell motility properties in SW480/lamA cells. PMID- 21983089 TI - Interaction forces between colloidal particles in a solution of like-charged, adsorbing nanoparticles. AB - We have measured the force between a weakly charged micron-sized colloidal particle and flat substrate in the presence of highly charged nanoparticles of the same sign under solution conditions such that the nanoparticles physically adsorb to the colloidal particle and substrate. The objective was to investigate the net effect on the force profile between the microparticle and flat substrate arising from both nanoparticle adsorption and nanoparticles in solution. The experiments used colloidal probe atomic force microscopy (CP-AFM) to measure the force profile between a relatively large (5 MUm) colloidal probe glass particle and a planar glass substrate in aqueous solutions at varying concentrations of spherical nanoparticles. At very low nanoparticle concentrations, the primary effect was an increase in the electrostatic repulsion between the surfaces due to adsorption of the more highly charged nanoparticles. As the nanoparticle concentration is increased, a depletion attraction formed, followed by longer range structural forces at the highest nanoparticle concentrations studied. These results suggest that, depending on their concentration, such nanoparticles can either stabilize a dispersion of weakly-charged colloidal particles or induce flocculation. This behavior is qualitatively different from that in nonadsorbing systems, where the initial effect is the development of an attractive depletion force. PMID- 21983090 TI - Superhydrophobic polyaniline hollow bars: constructed with nanorod-arrays based on self-removing metal-monomeric template. AB - Superhydrophobic hollow polyaniline (PANI) bars assembled from nanorod-arrays were prepared in the presence of metal-monomeric template. Toward preparing these PANI bars, self-assembling and "template" methods were simultaneously applied. The self-removing metal-monomeric "template" was probably formed when a high concentration of aniline (0.5 M) was added into the cadmium acetate solution, and then decomposed gradually during the oxidative polymerization of aniline. In addition, a superhydrophobic flower-like PANI hierarchical structure was also prepared without the "template" (cadmium acetate aqueous solution containing a low concentration of aniline (0.05 M)). The formation mechanism of the hollow PANI bars was discussed. PMID- 21983091 TI - Characterization and evaluation of miconazole salts and cocrystals for improved physicochemical properties. AB - Miconazole salts and cocrystals were studied to improve the physicochemical properties of miconazole. Maleate, hemifumarate, and hemisuccinate were prepared and characterized by powder X-ray diffractometry, differential scanning calorimetry, and single crystal X-ray diffractometry. The intrinsic dissolution rate and stability of each miconazole crystal form were compared to those of freebase and nitrate to evaluate the optimal crystal form. Crystal structure analysis indicated that maleate was a salt formed by proton transfer from the acid to the imidazole group of miconazole. Hemifumarate and hemisuccinate were determined to be cocrystals formed by hydrogen bonding between the acids and the base in their crystal lattices. Intrinsic dissolution tests showed that the formation of salts and cocrystals improved the dissolution rate of miconazole. Stability tests of preliminary formulations prepared with each crystal form indicated that maleate and hemifumarate were unstable at 80 degrees C and generated a specific degraded product, i.e., a Michael adduct, between miconazole and the acids. Hemisuccinate had a superior intrinsic dissolution rate and stability, and is thus considered a promising crystal form of miconazole. PMID- 21983092 TI - Controlled green tea polyphenols release from electrospun PCL/MWCNTs composite nanofibers. AB - Poly(E-caprolactone)/multi-walled carbon nanotubes (PCL/MWCNTs) composite nanofibers with various content of green tea polyphenols (GTP) were successfully fabricated via an electrospinning technology to maintain the chemical structural stability of GTP. The non-covalent interaction between MWCNTs and GTP was measured by UV-vis spectrophotometer and FT-IR. The topographical features of the nanofibers were characterized by scanning electron microscopy (SEM). The dispersibility of MWCNTs and the distribution of GTP in nanofibers were observed by transmission electron microscopy (TEM) and laser scanning confocal microscope (LSCM), respectively. In vitro degradation was also characterized in terms of the morphological change and the mass loss of the nanofiber meshes. In vitro GTP release behavior was investigated in phosphate-buffered solution (PBS) at 37 degrees C. Alamar blue assays were performed to estimate the cytotoxicity of the nanofibers with normal osteoblast cells and the antiproliferative effects to A549 and Hep G2 tumor cells. The results exhibited that the GTP-loaded composite nanofibers possessed a significant inhibition effect to tumor cells. Therefore, GTP, as a multifunctional drug, encapsulated into polymer composite nanofibers, must have broad application prospects in cancer therapy. PMID- 21983093 TI - Biodegradable hybrid recombinant block copolymers for non-viral gene transfection. AB - Thermal targeting of therapeutic genes can enhance local gene concentration to maximize their efficacy. However, lack of safe and efficient carriers has impeded the development of this delivery option. Herein, we report the preparation and evaluation of a hybrid recombinant material, p[Asp(DET)](53)ELP(1-90), that possess a thermo-responsive elastin-like polypeptide (ELP) segment and a diethylenetriamine (DET) modified poly-L-aspartic acid segment. The term, hybrid, indicates that the material was prepared by genetic engineering and synthetic chemistry. In summary, the thermal phase transition behavior and cytotoxicity of the biodegradable copolymer were studied. The polyplexes formed by the copolymer and pGL4 plasmid were characterized by dynamic light scattering and zeta potential measurements. The polyplexes retained the thermal phase transition behavior conferred by the copolymer; however, they exhibited a two-step transition process not seen with the copolymer. The polyplexes also showed appreciable transfection efficiency with low cytotoxicity. PMID- 21983094 TI - Real-time predictions of drug release and end point detection of a coating operation by in-line near infrared measurements. AB - The aim of this work was to carry out real-time near infrared (NIR) predictions of drug release from sustained release coated tablets and to determine end point of coating operation. In-line measurements were ensured by implementation of a NIR probe inside a pan coater. Tablets were coated using a functional aqueous dispersion of ethylcellulose blended with PVA-PEG graft copolymer to obtain a controlled drug release dosage form over 16h. Samples were collected at regular intervals and subjected to a standardized curing step. Percentages of released drug at 4h, 8h and 12h were selected to describe the controlled drug release of cured tablets. These dissolution criteria were used as reference values to calibrate NIR spectral information and to develop three partial least squares regressions. Low predictive errors of 1.7%, 1.9% and 1.5%, respectively, were obtained. The coating operation was stopped while desired dissolution criteria were achieved, corresponding to a coating level around 10%. The present study demonstrated that real-time NIR measurements could be performed on non-finished drug products to predict dissolution properties of cured coated tablets. This novel and innovative approach fulfils the expectations of ICH Q8 guideline on pharmaceutical development, in terms of process understanding and process analytical technology (PAT) control strategy. This approach should be however adapted to curing operation to allow a real-time release testing. PMID- 21983095 TI - Comparison of different protein concentration techniques within preformulation development. AB - Highly concentrated antibody solutions are of increasing importance in the pharmaceutical industry. During production highly concentrated solutions are usually prepared by tangential flow filtration (TFF). Since this technique is often not applicable in the early phase of formulation development, where the available amounts of protein are commonly very small, small scale techniques like dialysis or ultrafiltration with stirred cells or centrifugal filters have to be employed. In this study the small scale techniques were compared to tangential flow filtration, with regard to the quality and stability of the concentrated products. The achievable concentration of a protein, when starting from a model antibody solution with 10mg/ml, was also assessed. Concentrations above 100mg/ml could be obtained with all techniques, however with different product qualities. The stability of the highly concentrated solutions (100 mg/ml) was analyzed by turbidity measurements, size exclusion chromatography (SEC), SDS-PAGE and isoelectric focusing (IEF) after storage at 25 and 40 degrees C for 8 weeks. Solutions prepared by dialysis exhibited the smallest degree of instability, whereas those manufactured by centrifugal filtration revealed the best comparability to products obtained by tangential flow filtration with regard to the results of isoelectric focusing, turbidity measurements (UV-vis) and size exclusion chromatography. Stability differences were observed within all analytical methods, primarily after storage and not directly after the concentration process. PMID- 21983096 TI - Immunocytochemical staining for islet amyloid polypeptide in pancreatic endocrine tumors. AB - AIMS/HYPOTHESIS: Islet amyloid polypeptide is originally identified as the chief constituent of amyloid in insulinomas and type 2 diabetic islets. This study aimed to identify islet amyloid polypeptide by immunocytochemical staining in pancreatic endocrine tumors including 30 cases of insulinomas and non-beta-cell pancreatic endocrine tumors. RESULTS: In normal islets, 62% of islet cells and 52% of insulin cells were granularly positive for insulin and IAPP, respectively, with more insulin positive cells than IAPP positive cells and some densely positive staining for insulin and IAPP in irregularly shaped a nuclear, degenerating islet beta-cells. In pancreatic endocrine tumors, all 10 insulinomas were positive for islet amyloid polypeptide but 2 glucogonomas, 1 somatostatinoma, 6 of 7 pancreatic polypeptidomas, all 7 gastrinomas and all 3 non-functioning pancreatic endocrine tumors were negative for islet amyloid polypeptide whereas one pancreatic polypeptidoma was positive for islet amyloid polypeptide. METHODS: Using commercially available rabbit anti-islet amyloid polypeptide antibody, immunocytochemical staining was performed on 30 cases of pancreatic endocrine tumors, consisting of 10 insulinomas, 2 glucagonomas, 1 somatostatinoma, 7 pancreatic polypeptidomas, 7 gastrinomas and 3 non-functioning pancreatic endocrine tumors. Pancreatic tissues containing pancreatic endocrine tumors were systematically immunostained for insulin, glucagon, somatostatin, pancreatic polypeptide, gastrin and chromogranin A, in addition to islet amyloid polypeptide. When normal pancreatic tissues adjacent to pancreatic endocrine tumors were present, insulin, glucagon, somatostatin and islet amyloid polypeptide positive cells were counted for a total of 20 islets, which were divided into large islets and medium islets for each case. CONCLUSIONS/INTERPRETATIONS: All 10 insulinomas and 1 pancreatic polypeptidoma were granularly positive for islet amyloid polypeptide, suggesting all 10 insulinomas contained enough insulin granules for IAPP whereas only one non-beta cell pancreatic endocrine tumor was co-localized with islet amyloid polypeptide in their secretary granules. PMID- 21983097 TI - Effects of olmesartan and imidapril on the plasma adiponectin, P-selectin, and MDA-LDL levels of diabetic nephropathy patients. PMID- 21983098 TI - Calibrators for measuring aldosterone by liquid chromatography-tandem mass spectrometry. PMID- 21983099 TI - Nitric oxide infused in the solitary tract nucleus blocks brain glucose retention induced by carotid chemoreceptor stimulation. AB - Previous work has shown that the carotid body glomus cells can function as glucose sensors. The activation of these chemoreceptors, and of its afferent nucleus in the brainstem (solitary tract nucleus - STn), induces rapid changes in blood glucose levels and brain glucose retention. Nitric oxide (NO) in STn has been suggested to play a key role in the processing of baroreceptor signaling initiated in the carotid sinus. However, the relationship between changes in NO in STn and carotid body induced glycemic changes has not been studied. Here we investigated in anesthetized rats how changes in brain glucose retention, induced by the local stimulation of carotid body chemoreceptors with sodium cyanide (NaCN), were affected by modulation of NO levels in STn. We found that NO donor sodium nitroprusside (SNP) micro-injected into STn completely blocked the brain glucose retention reflex induced by NaCN chemoreceptor stimulation. In contrast, NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) increased brain glucose retention reflex compared to controls or to SNP rats. Interestingly, carotid body stimulation doubled the expression of nNOS in STn, but had no effect in iNOS. NO in STn could function to terminate brain glucose retention induced by carotid body stimulation. The work indicates that NO and STn play key roles in the regulation of brain glucose retention. PMID- 21983100 TI - TFPI-2 methylation predicts poor prognosis in non-small cell lung cancer. AB - BACKGROUND: Methylation of human tissue factor pathway inhibitor-2 (TFPI-2) gene has been detected in several types of cancer, including non-small cell lung cancer (NSCLC). However, an association between the methylation status of TFPI-2 gene and prognosis has not yet been investigated. METHODS: Methylation of TFPI-2 gene was examined in a consecutive series of 133 non-metastatic NSCLC patients using methylation-specific PCR (MSP). Univariate and multivariate analyses were conducted to investigate the association between clinical variables and overall survival time. RESULTS: Methylation of TFPI-2 gene was detected in 36 of 133 patients (27.1%). Of these 36 patients, seventeen individuals (47.2%) carried stage III tumors. The 5-year disease free survival rate among patients carrying methylated TFPI-2 tumors was significantly lower as compared to those with unmethylated TFPI-2 tumors (35.5% versus 6.1%, P<0.0001). Moreover, methylation of TFPI-2 gene was found to be an independent prognostic factor for poor overall survival based on multivariate analysis models (P=0.013), as was age >62 years old (P<0.0001) and TNM stage of disease (P<0.0001). CONCLUSIONS: The results of the present study suggest that methylation of TFPI-2 gene is an independent factor for an unfavorable prognosis in patients with NSCLC. PMID- 21983101 TI - Rpa43 and its partners in the yeast RNA polymerase I transcription complex. AB - An Rpa43/Rpa14 stalk protrudes from RNA polymerase I (RNAPI), with homology to Rpb7/Rpb4 (RNAPII), Rpc25/Rpc17 (RNAPIII) and RpoE/RpoF (archaea). In fungi and vertebrates, Rpa43 contains hydrophilic domains forming about half of its size, but these domains lack in Schizosaccharomyces pombe and most other eukaryote lineages. In Saccharomyces cerevisiae, they can be lost with little or no growth effect, as shown by deletion mapping and by domain swapping with fission yeast, but genetically interact with rpa12Delta, rpa34Delta or rpa49Delta, lacking non essential subunits important for transcript elongation. Two-hybrid data and other genetic evidence suggest that Rpa43 directly bind Spt5, an RNAPI elongation factor also acting in RNAPII-dependent transcription, and may also interact with the nucleosomal chaperone Spt6. PMID- 21983103 TI - Maffucci syndrome complicated with meningioma and pituitary adenoma. PMID- 21983102 TI - Decreases in valosin-containing protein result in increased levels of tau phosphorylated at Ser262/356. AB - VCP/p97 is a multifunctional AAA+-ATPase involved in vesicle fusion, proteasomal degradation, and autophagy. Reported dysfunctions of these processes in Alzheimer disease (AD), along with the linkage of VCP/p97 to inclusion body myopathy with Paget's disease and frontotemporal dementia (IBMPFD) led us to examine the possible linkage of VCP to the AD-relevant protein, tau. VCP levels were reduced in AD brains, but not in the cerebral cortex of an AD mouse model, suggesting that VCP reduction occurs upstream of tau pathology. Genetic reduction of VCP in a primary neuronal model led to increases in the levels of tau phosphorylated at Ser(262/356), indicating that VCP may be involved in regulating post translational processing of tau in AD, demonstrating a possible functional linkage between tau and VCP. PMID- 21983104 TI - Role of ghrelin system in neuroprotection and cognitive functions: implications in Alzheimer's disease. AB - Alzheimer's disease (AD) is a multifactorial progressive neurodegenerative disorder characterized by loss of memory and cognitive deficits, strongly influenced by the metabolic status, in which the impairment of neuropeptides/neurotransmitters systems has been previously observed. Ghrelin is a multifunctional hormone produced in a wide variety of tissues, which has been associated with the progression of obesity and metabolic syndrome, but has been also linked to neuromodulation, neuroprotection and memory and learning processes. In addition, ghrelin system also acts in an autocrine/paracrine fashion where the majority of its components [ghrelin variants (native ghrelin, In1-ghrelin), acylation enzyme (GOAT) and receptors (GHS-Rs)] are expressed in the different regions of central nervous system. In spite of all these pieces of information strongly suggesting a close association between ghrelin system and AD, which could be of pathophysiological relevance, few studies have been addressed to clarify this relationship. In this work, the role of ghrelin system in neuroprotection, memory consolidation and learning is reviewed, and its influence in AD, as well as the regulation of its expression in the brain of AD patients, is discussed. PMID- 21983105 TI - Endogenous opiates and behavior: 2010. AB - This paper is the thirty-third consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2010 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration (Section 16); and immunological responses (Section 17). PMID- 21983107 TI - Theoretical and experimental studies on the internal mobility of two sulfonylurea agents: glibenclamide and glimepiride. AB - Molecular dynamics of glibenclamide and glimepiride in their glassy state were studied by means of broadband dielectric spectroscopy. In both compounds we found a gamma-relaxation process, with nearly the same value of activation energy. Further, we were able to identify the origin of gamma relaxation by performing calculations within the framework of density functional theory. It was found that rotation of the chain end included cyclohexyl and neighboring carbonyl group is related to the observed mode in dielectric spectra. The calculated activation energy was only a few kJ per mole lower than the energies obtained from experiment. It is demonstrated that this fast gamma process is insensitive to pressure. Finally, another secondary mode in glibenclamide, predicted by computations, was confirmed from dielectric measurements at elevated pressure. Our calculations indicate that this mode should be pressure-sensitive. PMID- 21983106 TI - The action mechanisms of plant cryptochromes. AB - Cryptochromes (CRY) are blue-light receptors that mediate various light responses in plants. The photoexcited CRY molecules undergo several biophysical and biochemical changes, including electron transfer, phosphorylation and ubiquitination, resulting in conformational changes to propagate light signals. Two modes of CRY signal transduction have recently been discovered: the cryptochrome-interacting basic-helix-loop-helix 1 (CIB)-dependent CRY2 regulation of transcription; and the SUPPRESSOR OF PHYA1/CONSTITUTIVELY PHOTOMORPHOGENIC1 (SPA1/COP1)-dependent cryptochrome regulation of proteolysis. Both CRY signaling pathways rely on blue light-dependent interactions between the CRY photoreceptor and its signaling proteins to modulate gene expression changes in response to blue light, leading to altered developmental programs in plants. PMID- 21983108 TI - Lactic acid bacteria from chicken carcasses with inhibitory activity against Salmonella spp. and Listeria monocytogenes. AB - This study was conducted to isolate psychrotrophic lactic acid bacteria (LAB) from chicken carcasses with inhibitory activity against strains of Salmonella spp. and Listeria monocytogenes. A total of 100 broiler samples were examined for the presence of LAB. Ninety-two LAB isolates that showed antimicrobial effects against Salmonella spp. and L. monocytogenes were further analysed to examine their LAB (Gram-positive, catalase negative, oxidase negative) and psychrotrophic characteristics (ability to grow at 7 degrees C). Fifty isolates were further selected and identified initially using standard biochemical tests in miniature (Micro-kits API CH 50) and then by sequencing of the 16s-23s rRNA gene boundary region (Intergenic Spacer Region). By molecular identification, these isolates were classified into 5 different LAB species: Lactobacillus salivarius, Lactobacillus reuteri, Lactobacillus johnsonii, Pediococcus acidilactici, and Lactobacillus paralimentarius. None of the isolates produced tyramine or histamine. PMID- 21983109 TI - Brain oxygen tension monitoring following penetrating ballistic-like brain injury in rats. AB - While brain oxygen tension (PbtO(2)) monitoring is an important parameter for evaluating injury severity and therapeutic efficiency in severe traumatic brain injury (TBI) patients, many factors affect the monitoring. The goal of this study was to identify the effects of FiO(2) (fraction of inspired oxygen) on PbtO(2) in uninjured anesthetized rats and measure the changes in PbtO(2) following penetrating ballistic-like brain injury (PBBI). Continuous PbtO(2) monitoring in uninjured anesthetized rats showed that PbtO(2) response was positively correlated with FiO(2) (0.21-0.35) but PbtO(2) remained stable when FiO(2) was maintained at ~0.26. Importantly, although increasing FiO(2) from 0.21 to 0.35 improved P(a)O(2), it concomitantly reduced pH levels and elevated P(a)CO(2) values out of the normal range. However, when the FiO(2) was maintained between 0.26 and 0.30, the pH and P(a)O(2) levels remained within the normal or clinically acceptable range. In PBBI rats, PbtO(2) was significantly reduced by ~40% (16.9 +/- 1.2 mm Hg) in the peri-lesional region immediately following unilateral, frontal 10% PBBI compared to sham rats (28.6 +/- 1.7 mm Hg; mean +/- SEM, p<0.05) and the PBBI-induced reductions in PbtO(2) were sustained for at least 150 min post-PBBI. Collectively, these results demonstrate that FiO(2) affects PbtO(2) and that PBBI produces acute and sustained hypoxia in the peri lesional region of the brain injury. This study provides important information for the management of PbtO(2) monitoring in this brain injury model and may offer insight for therapeutic strategies targeted to improve the hypoxia/ischemia state in the penetrating-type brain injury. PMID- 21983110 TI - Bayesian nonparametric analysis of neuronal intensity rates. AB - We propose a flexible hierarchical Bayesian nonparametric modeling approach to compare the spiking patterns of neurons recorded under multiple experimental conditions. In particular, we showcase the application of our statistical methodology using neurons recorded from the supplementary eye field region of the brains of two macaque monkeys trained to make delayed eye movements to three different types of targets. The proposed Bayesian methodology can be used to perform either a global analysis, allowing for the construction of posterior comparative intervals over the entire experimental time window, or a pointwise analysis for comparing the spiking patterns locally, in a predetermined portion of the experimental time window. By developing our nonparametric Bayesian model we are able to analyze neuronal data from three or more conditions while avoiding the computational expenses typically associated with more traditional analysis of physiological data. PMID- 21983111 TI - The cost of clopidogrel use in atrial fibrillation in the ACTIVE-A trial. AB - BACKGROUND: The Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events-Aspirin (ACTIVE-A) demonstrated that in patients with atrial fibrillation unsuitable for vitamin K antagonist (VKA) therapy, a combination of clopidogrel and aspirin reduced stroke risk by 28% but increased major hemorrhage risk by 57%. This analysis examined cost implications of adding clopidogrel to aspirin (C+A) for ACTIVE-A patients. METHODS: Health care use was extracted for each patient. We considered only direct costs and included only hospitalization events. We used Canadian unit costs for the health care resources consumed and Canadian list price of brand clopidogrel. Costs, in 2008 Canadian dollars, were discounted at 3% per year. RESULTS: C+A reduced costs of health care use components except for the study medication. Stroke prevention resulted in important cost savings that offset the cost of clopidogrel. Total costs per patient for C+A were $14,132 (95% confidence interval [CI], $13,445-$14,842), compared with $13,756 (95% CI, $13,032-$14,544) for aspirin alone, resulting in incremental cost of $376 (95% CI, -$645 to $1397) for C+A, confirmed through bootstrap simulation. Estimates were sensitive to the price of clopidogrel, varying from cost savings to a significant increase. CONCLUSION: C+A in patients unsuitable for VKA therapy is cost neutral (following our predefined conditions) as cost of clopidogrel is offset by prevention of costly strokes. These findings support the use of C+A in ACTIVE-A patients for whom VKA therapy is unsuitable. PMID- 21983112 TI - Microaxial devices for ventricular failure: a multicentre, population-based experience. AB - BACKGROUND: Impella microaxial devices provide circulatory assistance for patients with acute decompensated heart failure. This study reviews the population-based provincial experience in British Columbia. METHODS: We performed a retrospective review of the prospectively maintained database. Impella devices were inserted for acute cardiogenic shock refractory to maximal therapy, as a bridge to decision or to long-term mechanical support. RESULTS: Between August 2007 and September 2009, 35 patients received 37 Impella devices (Impella LP 2,5, n=2; Impella LP 5,0, n=29; and Impella RD 5.0, n=6) (Abiomed Inc, Danvers, MA). Devices were inserted in the setting of dilated cardiomyopathy (n=13), acute myocardial infarction (n=6), postcardiotomy shock (n=6), and other etiologies (n=12). Mean age was 53.0+/-13.7 years. Mean left ventricular ejection fraction was 19+/-9% at the time of insertion. Nineteen patients required aggressive resuscitation, all patients were on inotropic support, 97% of patients were intubated, and 46% of patients received mechanical circulatory support prior to insertion of the Impella devices. Mean duration of support was 3.7+/-3.0 days. In all, 49% were successfully weaned, and 22% were transferred to long-term mechanical support. Four patients have subsequently undergone successful cardiac transplantation. The 30-day mortality was 40%, and 6-month mortality was 49%. Complications included gastrointestinal bleeding (n=1), hemoptysis (n=1), and thrombocytopenia (n=4). There were no cardiovascular or cerebrovascular events. CONCLUSION: Temporary support with Impella microaxial ventricular assist devices adds a valuable therapeutic option in selected patients with acute decompensated heart failure. PMID- 21983113 TI - Repeat cardiac surgery in a Jehovah's Witness patient with thrombocytopenia. AB - Complex cardiac surgery in Jehovah's Witness patients can be challenging, especially if it is a reoperation and the patient has a preexisting bleeding disorder. We operated on a patient who was declined for percutaneous aortic valve replacement and who required repeat surgery for aortic valve repeat replacement and root repair. In addition to being of Jehovah's Witness faith, the patient had chronic thrombocytopenia. We describe our strategy in managing this situation. PMID- 21983114 TI - Characterization of tissue biomechanics and mechanical signaling in uterine leiomyoma. AB - Leiomyoma are common tumors arising within the uterus that feature excessive deposition of a stiff, disordered extracellular matrix (ECM). Mechanical stress is a critical determinant of excessive ECM deposition and increased mechanical stress has been shown to be involved in tumorigenesis. Here we tested the viscoelastic properties of leiomyoma and characterized dynamic and static mechanical signaling in leiomyoma cells using three approaches, including measurement of active RhoA. We found that the peak strain and pseudo-dynamic modulus of leiomyoma tissue was significantly increased relative to matched myometrium. In addition, leiomyoma cells demonstrated an attenuated response to applied cyclic uniaxial strain and to variation in substrate stiffness, relative to myometrial cells. However, on a flexible pronectin-coated silicone substrate, basal levels and lysophosphatidic acid-stimulated levels of activated RhoA were similar between leiomyoma and myometrial cells. In contrast, leiomyoma cells plated on a rigid polystyrene substrate had elevated levels of active RhoA, compared to myometrial cells. The results indicate that viscoelastic properties of the ECM of leiomyoma contribute significantly to the tumor's inherent stiffness and that leiomyoma cells have an attenuated sensitivity to mechanical cues. The findings suggest there may be a fundamental alteration in the communication between the external mechanical environment (extracellular forces) and reorganization of the actin cytoskeleton mediated by RhoA in leiomyoma cells. Additional research will be needed to elucidate the mechanism(s) responsible for the attenuated mechanical signaling in leiomyoma cells. PMID- 21983115 TI - Laminin alpha1 is essential for mouse cerebellar development. AB - Laminin alpha1 (Lama1), which is a subunit of laminin-1 (laminin-111), a heterotrimeric ECM protein, is essential for embryonic development and promotes neurite outgrowth in culture. Because the deletion of Lama1 causes lethality at early embryonic stages in mice, the in vivo role of Lama1 in neural development and functions has not yet been possible to determine. In this study, we generated conditional Lama1 knockout (Lama1(CKO)) mice in the epiblast lineage using Sox2 Cre mice. These Lama1(CKO) mice survived, but displayed behavioral disorders and impaired formation of the cerebellum. Deficiency of Lama1 in the pial basement membrane of the meninges resulted in defects in the conformation of the meninges. During cerebellar development, Lama1 deficiency also caused a decrease in the proliferation and migration of granule cell precursors, disorganization of Bergmann glial fibers and endfeet, and a transient reduction in the activity of Akt. A marked reduction in numbers of dendritic processes in Purkinje cells was observed in Lama1(CKO) mice. Together, these results indicate that Lama1 is required for cerebellar development and functions. PMID- 21983116 TI - Membrane topology screen of secondary transport proteins in structural class ST[3] of the MemGen classification. Confirmation and structural diversity. AB - The MemGen structural classification of membrane proteins groups families of proteins by hydropathy profile alignment. Class ST[3] of the MemGen classification contains 32 families of transporter proteins including the IT superfamily. Transporters from 19 different families in class ST[3] were evaluated by the TopScreen experimental topology screening method to verify the structural classification by MemGen. TopScreen involves the determination of the cellular disposition of three sites in the polypeptide chain of the proteins which allows for discrimination between different topology models. For nearly all transporters at least one of the predicted localizations is different in the models produced by MemGen and predictor TMHMM. Comparison to the experimental data showed that in all cases the prediction by MemGen was correct. It is concluded that the structural model available for transporters of the [st324]ESS and [st326]2HCT families is also valid for the other families in class ST[3]. The core structure of the model consists of two homologous domains, each containing 5 transmembrane segments, which have an opposite orientation in the membrane. A reentrant loop is present in between the 4th and 5th segments in each domain. Nearly all of the identified and experimentally confirmed structural variations involve additions of transmembrane segments at the boundaries of the core model, at the N- and C-termini or in between the two domains. Most remarkable is a domain swap in two subfamilies of the [st312]NHAC family that results in an inverted orientation of the proteins in the membrane. PMID- 21983118 TI - Comparison of three lubricant eye drop solutions in dry eye patients. AB - PURPOSE: Lubricant eye drops that restore physiological osmolarity represent a promising strategy for dry eye syndrome as hyperosmolarity plays a central role in this disease. This preliminary study compared three lubricant eye drop solutions with different osmolarities and compositions in subjects with this condition. METHODS: Subjects with dry eye syndrome undergoing treatment with benzalkonium chloride-containing lubricant eye drops were randomized to Carnidrop (n = 9), Optive (n = 9), or Blu Sal (n = 9). Fluorescein break-up time (FBUT) and Ocular Protection Index (OPI) were measured at baseline, 15 min, and 60 min after instillation to evaluate the stability and quality of the tear film. RESULTS: At 15 min, a significant increase in FBUT vs. baseline was reported with Carnidrop (from 2.0 +/- 0.8 to 4.8 +/- 2.0; p = 0.004) but not in patients who received Optive or Blu Sal. At 60 min, FBUT was significantly increased vs. baseline with Carnidrop (from 2.0 +/- 0.8 to 6.0 +/- 2.8, p = 0.001) and Optive (from 2.9 +/- 2.8 to 4.3 +/- 2.9, p = 0.004) but not with Blu Sal. At 15 min, OPI was significantly increased from baseline in only the Carnidrop group (from 0.4 +/- 0.2 to 1.0 +/- 0.4, p = 0.003). This increase was significantly greater with Carnidrop than with Blu Sal (p = 0.003). At the 60 min evaluation, OPI remained significantly increased from baseline in only the Carnidrop group (p = 0.003). CONCLUSIONS: Carnidrop produces a larger increase in FBUT and OPI than Optive and Blu Sal in subjects with dry eye syndrome over a 1 h period, possibly because of its hypo-osmolarity and high osmolyte (in particular L-carnitine) content. The instillation of compounds that improve the quality and stability of the tear film, which are impaired in dry eye syndrome, could be effective in the treatment of this condition. PMID- 21983117 TI - Increased caspase activity primes human Lyme arthritis synovial gammadelta T cells for proliferation and death. AB - gammadelta T cells function between the innate and adaptive immune responses, promoting antigen-presenting cell function and manifesting cytolytic activity. Their numbers often increase during infections, such as human immunodeficiency virus, and at sites of chronic inflammation. However, the turnover dynamics of human gammadelta T cells are poorly understood. Here we observed that despite more rapid proliferation in vitro by human Lyme arthritis synovial gammadelta T cells of the Vdelta1 subset, they have reduced surviving cell numbers compared with alphabeta T cells because of increased cell death by the gammadelta T cells. Because caspases are involved in cell proliferation and death, and because signaling is more efficient through T cell receptor (TCR)-gammadelta than through TCR-alphabeta, we examined the levels of active caspases during cell cycling and following TCR restimulation. We observed higher overall caspase activity in Borrelia-reactive gammadelta T cells than in comparable alphabeta T cells. This was paralleled by greater spontaneous cell death and TCR restimulation-induced cell death of the gammadelta T cells, which was caspase dependent. Our current findings thus are consistent with a model in which human gammadelta T cells evolved to function quickly and transiently in an innate fashion. PMID- 21983119 TI - Adaptive astigmatism-correcting device for eyepieces. AB - PURPOSE: We describe how to construct a low-cost and robust variable astigmatism correcting device manufactured using a pair of identical commercial ophthalmic lenses. METHODS: Variable astigmatism power can be obtained by relative rotation of two cross cylinders with the same prescription (for this work: S = +2.00 D, C = -4.00 D was used). The rotation of the whole ensemble allows the user to choose the astigmatism axis. RESULTS: The lens system presented here is able to correct astigmatism for eyepieces, compensating eyeglasses prescriptions from -8.00 to 0.00 D without generation of higher order aberrations and always with mean sphere power close to 0. Theoretical description of the piece, calibration, measurement of aberrations, and examples of use within a microscope are included. CONCLUSIONS: An inexpensive and robust variable-astigmatism device for eyepieces can be manufactured using two equal ophthalmic lenses. The system is robust in the sense that small misalignments only minimally affect mean sphere power and do not affect higher order aberrations. This unique device can be adapted to many users. PMID- 21983120 TI - Myopia progression rates in urban children wearing single-vision spectacles. AB - PURPOSE: To conduct a meta-analysis on the rates of myopia progression in urban children of Asian and predominately European ethnicities who are corrected with traditional single-vision spectacles. METHODS: A search of the National Library of Medicine's PubMed literature database for articles on myopia progression was conducted using the terms "myopi*progression" and MeSH terms "myopia" and "disease progression," and limited to publications from January 1990 and only for articles reporting data for humans <16 years of age. Studies were excluded if they were non-randomized, did not use cycloplegic autorefraction, had a sample size <30 individuals, examined high myopia (worse than -6.0 D) or special subject groups, presented myopia as part of a syndrome or condition, were retrospective, or used controls wearing optical corrections other than spectacles. RESULTS: Of 175 articles identified, 20 remained after applying the exclusion criteria. The estimated myopia progression at a mean age of 9.3 years after 1 year of follow-up was -0.55 D [95% confidence interval (CI), -0.39 to -0.72 D] for populations of predominantly European extraction and -0.82 D (95% CI, -0.71 to -0.93 D) for Asians. The estimated progression rates were dependent on baseline age, with decreasing progression as age increased. The rates also varied with gender. For an average baseline age of 8.8 years, estimated annual progression (combined ethnicities) was -0.80 D/yr for females (95% CI, -0.51 to -1.10), and a significantly slower (p < 0.01) -0.71 D/yr for males (95% CI, -0.42 to -1.00). CONCLUSIONS: In children wearing single-vision spectacles, higher myopia progression rates were found in urban Asians compared with urban populations of predominantly European descent. Younger children and females demonstrated greater annual rates of progression of myopia. PMID- 21983121 TI - Changes in peripapillary retinal nerve fiber layer distribution by axial length. AB - PURPOSE: To investigate the effect of axial length on the peripapillary retinal nerve fiber layer (RNFL) distribution and the risk of misdiagnosing normal subjects when using the instrument's built-in normative database. METHODS: Healthy young volunteers underwent ophthalmologic examinations including RNFL thickness analysis with spectral-domain optical coherence tomography (OCT), autorefraction, and axial length measurement. The average RNFL thickness values reported along the calculation circle for whole circle, quadrants, and clock hours were recorded and evaluated at the 5% probability level for significant disparities in comparison with the built-in RNFL database. Angular locations with maximal RNFL thickness in the superotemporal and inferotemporal RNFL humps were determined. The relationships of axial length with these variables were analyzed using both linear regression and logistic regression models. RESULTS: A total of 485 eyes of 485 subjects were analyzed. The average 360 degrees RNFL thickness became thinner as the axial length increased (r = -0.244, p < 0.001). As the axial length increased, the average RNFL thicknesses in the 1, 2, 4, 5, 6, and 12 o'clock hour sectors decreased whereas those of the 7, 8, 9, 10, and 11-o'clock hour sectors increased. In addition, as the axial length increased, two major RNFL humps were located more temporally and it became significantly more likely for the 1, 2, 5, 6, and 12-o'clock hour sectors to fall below the p < 0.05 significance limits for normal thickness. CONCLUSIONS: Peripapillary RNFL thickness changes differently in different peripapillary locations as axial length increases. Because long eyes may lead to misleading findings of OCT parameters depending on the peripapillary location, their relationship to the axial length should be considered in the built-in RNFL thickness normative database of OCT. PMID- 21983122 TI - Multifocal pupillographic assessment of age-related macular degeneration. AB - PURPOSE: To investigate retinal function in subjects with unilateral exudative age-related macular degeneration (AMD) using multifocal pupillographic objective perimetry (mfPOP) and to assess the diagnostic accuracy of this technique. METHODS: We tested each of 20 exudative AMD patients and 20 control subjects with 4 different mfPOP stimulus variants. Multifocal stimuli consisting of 24 or 44 independent stimulus regions per eye extending from fixation to 15 degrees eccentricity were presented dichoptically. The aperiodic stimuli were presented at 1 or 4 s mean intervals. Video cameras recorded pupil responses under infrared illumination. Test duration consisted of 8 segments of 30 s. Stimuli were presented at a luminance of 250 cd/m and a background of 10 cd/m. Peak regional contraction amplitudes, time to peaks, and a linear combination of these were used to produce receiver operator characteristic (ROC) curves to measure the diagnostic accuracy of this method. RESULTS: Mean constriction amplitudes of exudative AMD subjects were decreased by 0.77 +/- 0.15 dB (p < 5 * 10). Stimulus ensembles with 44 regions and faster presentation rates produced the largest effect on response sizes (t = 3.63; p < 0.0002). When comparing the control eyes to exudative AMD eyes, the area under the curve of ROC plots was 0.96 +/- 0.03 (mean +/- SE). This was achieved for asymmetry analysis of the difference in response amplitudes obtained from the two eyes at each point in the visual field. CONCLUSIONS: The mean effect of exudative AMD on contraction amplitudes reflected the severity of disease, and ROC analysis from amplitude deviations improved the sensitivity of detection of exudative AMD. A longitudinal investigation into the mfPOP responses of patients with non-exudative AMD may detect and classify visual fields with poor prognosis. PMID- 21983123 TI - Therapeutic hypothermia and prevention of acute kidney injury: a meta-analysis of randomized controlled trials. AB - BACKGROUND: Therapeutic hypothermia has been shown to reduce neurological morbidity and mortality in the setting of out-of-hospital cardiac arrest and may be beneficial following brain injury and cardiopulmonary bypass. We conducted a systematic review to ascertain the effect of therapeutic hypothermia on development of acute kidney injury (AKI) and mortality. METHODS: We searched for randomized controlled trials in MEDLINE through February 2011. We included trials comparing hypothermia to normothermia that reported kidney-related outcomes including, development of AKI, dialysis requirement, changes in serum creatinine, and mortality. We performed Peto fixed-effect and random-effects model meta analyses, and meta-regressions. RESULTS: Nineteen trials reporting on 2218 patients were included; in the normothermia group, the weighted rate of AKI was 4.2%, dialysis requirement 3.7%, and mortality 10.8%. By meta-analysis, hypothermia was not associated with a lower odds of AKI (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.68, 1.51; P=0.95) or dialysis requirement (OR 0.81; 95% CI 0.30, 2.19; P=0.68); however, by meta-regression, a lower target cooling temperature was associated with a lower odds of AKI (P=0.01). Hypothermia was associated with lower mortality (OR 0.69; 95% CI 0.51, 0.92; P=0.01). CONCLUSIONS: In trials that ascertained kidney endpoints, therapeutic hypothermia prevented neither the development of AKI nor dialysis requirement, but was associated with lower mortality. Different definitions and rates of AKI, differences in mortality rates, and concerns about the optimal target cooling temperature preclude definitive conclusions. PMID- 21983124 TI - Predicting non-cardiac aetiology: a strategy to allocate rescue breathing during bystander CPR. AB - AIMS: Optimal care for out-of hospital cardiac arrest (OHCA) patients may depend on the underlying aetiology of OHCA. Specifically chest compression only bystander CPR may provide greater benefit among those with cardiac aetiology and chest compressions plus rescue breathing may provide greater benefit among those with non-cardiac aetiology. The aim of this study was to generate a simple predictor model to identify OHCA patients with non-cardiac aetiology in order to accurately allocate rescue breathing. METHODS: We used two independent cohorts of OHCA patients from a randomized pre-hospital trial and a prospective hospital registry (total n=3086) to assess whether the characteristics of age, gender and arrest location (private versus public) could sufficiently discriminate non cardiac aetiology. We used logistic regression models to generate a receiver operator curve and likelihood ratios. RESULTS: Overall, 965/3086 (31%) had a final diagnosis of a non-cardiac cause. Using 8 exclusive groups according to age, gender, and location, the frequency of non-cardiac aetiology varied from a low of 16% (55/351) among men >age 50 in a public location up to 58% (199/346) among women <60 in a private location. Although each characteristic was predictive in the logistic regression model, the area under the curve in the receiver operating curve was only 0.66. The associated positive likelihood ratios ranged from 1 to 3 and the negative likelihood ratios ranged from 1 to 0.4. CONCLUSION: The results highlight the challenge of accurately identifying non cardiac aetiology by characteristics that could be consistently used to allocate bystander rescue breathing. PMID- 21983125 TI - Interferon gamma receptor expression on granulocytes of cardiac surgical patients is modulated differently by the type of cardiopulmonary bypass used. AB - AIMS: To follow the IFNgamma receptor expression on monocytes and granulocytes of cardiac surgical patients with respect to the type of cardiopulmonary bypass (CPB). METHODS: Expression of IFNgamma receptor on monocytes and granulocytes of 26 cardiac surgical patients operated with the use of either "standard" or "miniaturised" CPB was determined by flow cytometry. RESULTS: The significant increase in IFNgamma receptor expression on monocytes on the 1(st) and on the 3(rd) postoperative days was revealed in both groups of patients (p<0.001) irrespective of the type of CPB used, being non-significantly different between groups. In contrast, the expression of IFNgamma on granulocytes displayed significant differences in terms of the CPB used. Whereas, in "standard" CPB patients, granulocyte INFgamma receptor expression reached its maximum immediately after surgery (p<0.01), in "miniivasive" CPB patients, the peak in INFgamma receptor expression was postponed to the 1(st) postoperative day (p<0.05). Statistically significantly higher IFNgamma receptor expression on granulocytes was found in "standard" CPB patients (p<0.05). CONCLUSION: Compared to "miniaturised" CPB patients, the significantly higher IFNgamma receptor expression on granulocytes was found in "standard" CPB patients (p<0.05) on the 1(st) postoperative day. PMID- 21983126 TI - The meaning of "aging in place" to older people. AB - PURPOSE: This study illuminates the concept of "aging in place" in terms of functional, symbolic, and emotional attachments and meanings of homes, neighbourhoods, and communities. It investigates how older people understand the meaning of "aging in place," a term widely used in aging policy and research but underexplored with older people themselves. DESIGN AND METHODS: Older people (n = 121), ranging in age from 56 to 92 years, participated in focus groups and interviews in 2 case study communities of similar size in Aotearoa New Zealand, both with high ratings on deprivation indices. The question, "What is the ideal place to grow older?" was explored, including reflections on aging in place. Thematic and narrative analyses on the meaning of aging in place are presented in this paper. RESULTS: Older people want choices about where and how they age in place. "Aging in place" was seen as an advantage in terms of a sense of attachment or connection and feelings of security and familiarity in relation to both homes and communities. Aging in place related to a sense of identity both through independence and autonomy and through caring relationships and roles in the places people live. IMPLICATIONS: Aging in place operates in multiple interacting ways, which need to be taken into account in both policy and research. The meanings of aging in place for older people have pragmatic implications beyond internal "feel good" aspects and operate interactively far beyond the "home" or housing. PMID- 21983127 TI - MicroRNA-150 directly targets MUC4 and suppresses growth and malignant behavior of pancreatic cancer cells. AB - Pancreatic cancer (PC) has the worst prognosis among all cancers due to its late diagnosis and lack of effective therapies. Therefore, identification of novel gene targets, which are differentially expressed in PC and functionally involved in malignant phenotypes, is critical to achieve early diagnosis and development of effective therapeutic strategies. We have shown previously that MUC4, an aberrantly overexpressed transmembrane mucin, promotes growth, invasion and metastasis of PC cells, thus underscoring its potential as a clinical target. Here, we report a novel microRNA (miRNA)-mediated mechanism underlying aberrant expression of MUC4 in PC. We demonstrate that the 3' untranslated region of MUC4 contains a highly conserved miRNA-150 (miR-150) binding motif and its direct interaction with miR-150 downregulates endogenous MUC4 protein levels. We also show that miR-150-mediated MUC4 downregulation is associated with a concomitant decrease in human epidermal growth factor receptor 2 and its phosphorylated form, leading to reduced activation of downstream signaling. Furthermore, our findings demonstrate that miR-150 overexpression inhibits growth, clonogenicity, migration and invasion and enhances intercellular adhesion in PC cells. Finally, our data reveal a downregulated expression of miR-150 in malignant pancreatic tissues, which is inversely associated with MUC4 protein levels. Altogether, these findings establish miR-150 as a novel regulator of MUC4 and a tumor suppressor miRNA in PC. PMID- 21983128 TI - Ling Zhi-8 mediates p53-dependent growth arrest of lung cancer cells proliferation via the ribosomal protein S7-MDM2-p53 pathway. AB - Ling Zhi-8 (LZ-8), an immunomodulatory protein, is derived from and has been cloned from the medicinal mushroom Ganoderma lucidum (Reishi or Ling Zhi); this protein exhibits immunomodulating and antitumor properties. We investigated the effects of recombinant LZ-8 protein (rLZ-8) on the proliferation of A549 human lung cancer cells. Here, we showed that rLZ-8 inhibits cell growth and that this is correlated with increased G(1) arrest. The treatment of A549 cells with rLZ-8 activated p53 and p21 expression, and both the G(1) arrest and the antigrowth effect were found to be p53 dependent. It was further demonstrated that rLZ-8 inhibited tumor growth in mice transplanted with Lewis lung carcinoma cells. Interestingly, rLZ-8 treatment was found to lead to nucleolar stress (or ribosomal stress) as evidenced by inhibition of precursor ribosomal RNA synthesis and reduced polysome formation in A549 cells. These changes resulted in an increasing binding of ribosomal protein S7 to MDM2 and a decreased interaction between MDM2 and p53. Taking these results together, we have identified a novel rLZ-8 antitumor function that positively modulates p53 via ribosomal stress and inhibits lung cancer cell growth in vitro and in vivo. Our current results suggest that rLZ-8 may have potential as a therapeutic intervention for the treatment of cancers that contain wild-type p53 and high expression of MDM2. PMID- 21983129 TI - Suppression of viral replication by drs tumor suppressor via mTOR dependent pathway. AB - The drs gene is an apoptosis-inducing tumor suppressor. By using drs-knockout (KO) mouse embryonic fibroblasts (MEFs), we showed that drs is involved in the host defense against viral infection. In drs-KO MEFs infected with vesicular stomatitis virus, the viral replication and protein synthesis were markedly enhanced without the upregulation of the cellular protein synthesis. Phosphorylation of S6K, S6, 4EBP1 and TSC2 proteins was closely correlated with the enhanced viral replication in drs-KO MEFs. Drs protein could associate with stress-inducible GADD34 to form a complex with TSC1/2, which suppresses mTOR activity. These findings indicate that Drs suppresses viral replication via mTOR dependent pathway. PMID- 21983130 TI - Expression of the tumor suppressor miR-206 is associated with cellular proliferative inhibition and impairs invasion in ERalpha-positive endometrioid adenocarcinoma. AB - This study investigated the role of miR-206 in estrogen receptor-alpha (ERalpha) positive endometrial endometrioid adenocarcinoma (EEC). We profiled miR-206 expression in 30 EEC clinical samples using qRT-PCR, and explored its relationship with ERalpha and clinical parameters. A luciferase reporter assay assessed the ERalpha targeting potential of miR-206. Functional analyses of miR 206 were performed in EEC cell lines. MiRNA-206 expression decreased in ERalpha positive EECs, and its expression was negatively correlated with ERalpha. MiRNA 206 overexpression inhibited ERalpha-dependent proliferation, impaired invasiveness and induced cell cycle arrest of ERalpha-positive EEC cell lines. Therefore, aberrantly expressed miRNA-206 may be associated with the development of ERalpha-positive EEC. PMID- 21983131 TI - Surviving cells after treatment with gemcitabine or 5-fluorouracil for the study of de novo resistance of pancreatic cancer. AB - One of the hallmarks of pancreatic cancer is its inherent insensitivity to chemotherapy. This study was undertaken to develop a cell model for the study of de novo resistance of pancreatic cancer. The surviving pancreatic cancer cells after a 3-day exposure to gemcitabine or 5-fluorouracil followed by another 7-day recovery were potentially drug-resistant. They had similar morphology and comparable growth and tumorigenic potentials to their untreated parental cells. Repeated subculture affected the cell-cycle profile and growth characteristics of the surviving cells. Our data suggest that surviving pancreatic cancer cells after drug treatment are a useful model for exploring intrinsic resistance. PMID- 21983132 TI - Viral epidemiology of acute exacerbations of chronic obstructive pulmonary disease. AB - The role of viruses in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) needs further elucidation. The aim of the present study was to evaluate the molecular epidemiology of viral pathogens in AECOPD. Patients presenting to the Emergency Room with AECOPD needing hospitalization were recruited. Oropharyngeal and sputum samples were collected in order to perform microarrays-based viral testing for the detection of respiratory viruses. A total of 200 (100%) patients were analyzed and from them in 107 (53.5%) a virus was detected. The commonest identified viruses were the human Respiratory Syncytial Virus (subtypes A and B) (40.5%), influenza virus (subtypes A, B, C) (11%), rhinovirus (8%) and human Parainfluenza Virus (subtypes A and B) (7.5%). A bacterial pathogen was isolated in 27 (14%) patients and a dual infection due to a bacterial and a viral pathogen was recognised in 14/107 patients. Patients with AECOPD and a viral infection had a lengthier hospital stay (9.2 +/- 4.6 vs 7.6 +/ 4.3, p < 0.01) while the severity of the disease was no related with significant differences among the groups of the study population. In conclusion, the isolation of a virus was strongly associated with AECOPD in the examined population. The stage of COPD appeared to have no relation with the frequency of the isolated viruses while dual infection with a viral and a bacterial pathogen was not rare. PMID- 21983133 TI - A new model for calculating auditory excitation patterns and loudness for cases of cochlear hearing loss. AB - A model for calculating auditory excitation patterns and loudness for steady sounds for normal hearing is extended to deal with cochlear hearing loss. The filters used in the model have a double ROEX-shape, the gain of the narrow active filter being controlled by the output of the broad passive filter. It is assumed that the hearing loss at each audiometric frequency can be partitioned into a loss due to dysfunction of outer hair cells (OHCs) and a loss due to dysfunction of inner hair cells (IHCs). OHC loss is modeled by decreasing the maximum gain of the active filter, which results in increased absolute threshold, reduced compressive nonlinearity and reduced frequency selectivity. IHC loss is modeled by a level-dependent attenuation of excitation level, which results in elevated absolute threshold. The magnitude of OHC loss and IHC loss can be derived from measures of loudness recruitment and the measured absolute threshold, using an iterative procedure. The model accurately fits loudness recruitment data obtained using subjects with unilateral or highly asymmetric cochlear hearing loss who were required to make loudness matches between tones presented alternately to the two ears. With the same parameters, the model predicted loudness matches between narrowband and broadband sound reasonably well, reflecting loudness summation. The model can also predict when a dead region is present. PMID- 21983134 TI - Whispering gallery mode biosensor quantification of fibronectin adsorption kinetics onto alkylsilane monolayers and interpretation of resultant cellular response. AB - A Whispering Gallery Mode (WGM) biosensor was constructed to measure the adsorption of protein onto alkysilane self-assembled monolayers (SAMs) at solution concentrations unattainable with other techniques. The high sensitivity was provided by a WGM resonance excited in a silica microsphere that was functionalized with alkylsilane SAMs and integrated in a microfluidic flow cell under laminar flow conditions. It was found that FN adsorbed at biologically relevant surface densities, however, the adsorption kinetics and concentration dependent saturation values varied significantly from work published utilizing alkanethiol SAMs. Mathematical models were applied to the experimental results to interpret the observed kinetics of FN adsorption. Embryonic hippocampal neurons and skeletal myoblasts were cultured on the modified surfaces, a live--dead assay was used to determine the viability of the FN surfaces for cell culture, and major differences were noted in the biological response to the different SAMs. The high sensitivity and simplicity of the WGM biosensor, combined with its ability to quantify the adsorption of any dilute protein in a label-free assay, establishes the importance of this technology for the study of surface accretion and its effect on cellular function, which can affect biomaterials for both in vivo and in vitro applications. PMID- 21983135 TI - The application of an alanine-substituted mutant of the C-terminal fragment of Clostridium perfringens enterotoxin as a mucosal vaccine in mice. AB - Efficient delivery of antigen to mucosal immune tissues is an essential part of mucosal vaccination. Claudin-4 is expressed on the epithelial cells that cover the mucosal immune tissues. We previously found that claudin-4-targeting is a promising strategy for mucosal vaccination by using a claudin-4 binder, the C terminal fragment of Clostridium perfringens enterotoxin (C-CPE). Substitution of Asn and Ser at positions 309 and 313, respectively, with alanine increased the affinity of C-CPE for claudin-4. However, application of the C-CPE mutant as a mucosal vaccine has never been tried. Here, we investigated whether the C-CPE mutant could serve as a mucosal vaccine. We used ovalbumin (OVA) as a model antigen and fused the C-CPE mutant to it. The resultant fusion protein was bound to claudin-4. When mice were immunized with the C-CPE mutant-fused OVA, OVA specific serum IgG and nasal IgA increased relative to levels in mice immunized with a C-CPE-fused antigen. Immunization with the C-CPE mutant-fused OVA activated Th1- and Th2-type responses and led to increased anti-tumor activity against OVA-expressing thymoma cells relative to that of mice immunized with the C-CPE-fused antigen. These findings suggest that the alanine-substituted C-CPE mutant shows promise as a claudin-targeted mucosal vaccine. PMID- 21983136 TI - Mitochondrial targeting liposomes incorporating daunorubicin and quinacrine for treatment of relapsed breast cancer arising from cancer stem cells. AB - Breast cancer stem cells play a crucial role in the relapse of breast cancers because they are resistant to a standard chemotherapy and the residual cancer stem cells are able to proliferate indefinitely. The objectives of present study were to construct a kind of mitochondrial targeting daunorubicin plus quinacrine liposomes for treating and for preventing the recurrence of breast cancer arising from the cancer stem cells. MCF-7 cancer stem cells were identified as CD44(+)/CD24(-) cells and cultured in free-serum medium. Evaluations were performed on MCF-7 cancer stem cells, MCF-7 cancer stem cell mammospheres, and the relapsed tumor by xenografting MCF-7 cancer stem cells into female NOD/SCID mice. The particle size of mitochondrial targeting daunorubicin plus quinacrine liposomes was approximately 98 nm. The mitochondrial targeting liposomes evidently increased the mitochondrial uptake of drugs, were selectively accumulated into mitochondria, activated the pro-apoptotic Bax protein, dissipated the mitochondrial membrane potential, opened the mitochondrial permeability transition pores, released cytochrome C by translocation, and initiated a cascade of caspase 9 and 3 reactions, thereby inducing apoptosis of MCF-7 cancer stem cells. The mitochondrial targeting liposomes showed the strongest efficacy in treating MCF-7 cancer cells in vitro, in treating MCF-7 cancer stem cells in vitro, and in treating the relapsed tumor in mice. Mitochondrial targeting daunorubicin plus quinacrine liposomes would provide a new strategy for treating and preventing the relapse of breast cancers arising from cancer stem cells. PMID- 21983137 TI - The phagocytosis of gas-filled microbubbles by human and murine antigen presenting cells. AB - This study was designed to evaluate the potential of gas-filled microbubbles (MB) to be internalized by antigen-presenting cells (APC). Fluorescently labeled MB were prepared, thus permitting to track binding to, and internalization in, APC. Both human and mouse cells, including monocytes and dendritic cells (DC), prove capable to phagocyte MB in vitro. Observation by confocal laser scanning microscopy showed that interaction between MB and target cells resulted in a rapid internalization in cellular compartments and to a lesser extent in the cytoplasm. Capture of MB by APC resulted in phagolysosomal targeting as verified by double staining with anti-lysosome-associated membrane protein-1 monoclonal antibody and decrease of internalization by phagocytosis inhibitors. Fluorescent MB injected subcutaneously (s.c.) in mice were found to be associated with CD11c(+)DC in lymph nodes draining the injection sites 24 h after administration. Altogether, our study demonstrates that MB can successfully target APC both in vitro and in vivo, and thus may serve as a potent Ag delivery system without requirement for ultrasound-based sonoporation. This adds to the potential of applications of MB already extensively used for diagnostic imaging in humans. PMID- 21983138 TI - Renal distal tubule proliferation and increased aquaporin 2 level but decreased urine osmolality in db/db mouse: treatment with chromium picolinate. AB - Hallmark features of type 2 diabetes mellitus include glucosuria and polyuria. Further, renal aquaporin 2 is pivotal to regulation of fluid excretion and urine osmolality. Accordingly, we tested the hypothesis that the db/db mouse displays increased glucosuria and fluid excretion but reduced urine osmolality in association with decreased renal aquaporin 2 level. In addition, we examined the effect of chromium picolinate (Cr(pic)3) which is purported to improve glycemic control. The db/db mice excreted more urine in association with marked glucose excretion but lower urine osmolality than db/m control group. Light microscopic examination of renal tissue revealed proliferation of tubular structures in db/db compared to the db/m mice, a feature validated with Ki67 immunostaining. Further, these tubules showed generally similar immunostaining intensity and pattern for aquaporin 2 indicating that proliferated tubules are of distal origin. On the other hand, renal aquaporin 2 protein level was significantly higher in the db/db than db/m group. Treatment of db/db mice with Cr(pic)3 reduced plasma glucose and hemoglobin A1c (~15-17%, p<0.05) and Ki67 positive cells but other parameters were similar to their untreated counterparts. Collectively, these findings suggest that proliferation of renal distal tubules and increased aquaporin 2 level likely represent an adaptive mechanism to regulate fluid excretion to prevent dehydration in the setting of marked glucosuria in the db/db mouse, features not affected by Cr(pic)3 treatment. These observations are of relevance to increasing interest in developing therapeutic agents that facilitate renal glucose elimination. PMID- 21983139 TI - Graminan breakdown by fructan exohydrolase induced in winter wheat inoculated with snow mold. AB - Fructan structures vary widely among plant species. Graminan-type fructans, extensions of sucrose through beta-(2,6)-linked fructosyl units with branches of beta-(2,1)-linked fructosyl units, accumulate in tissues of winter wheat (Triticum aestivum) during cold hardening and are metabolized under persistent snow cover. Snow molds such as Typhula ishikariensis and Microdochium nivale opportunistically infect wheat under snow cover. Snow mold-resistant wheat cultivars tend to heavily accumulate and slowly metabolize water-soluble carbohydrates including graminans in comparison with snow mold-susceptible cultivars. We observed time-dependent changes in the amounts of water-soluble carbohydrates in snow mold-inoculated wheat tissues, and accumulated fructan levels significantly decreased as a result of snow mold inoculation and incubation under snow cover, especially in a snow mold-susceptible wheat cultivar. Three candidates for fructan exohydrolase (FEH) cDNAs with high homology to cell wall invertases were isolated from wheat leaf tissues inoculated with snow mold and incubated under snow cover. The substrate specificity of enzymes encoded by the isolated clones was analyzed by recombinant proteins expressed in Pichia pastoris. The recombinant protein (Wfh-sm3m) encoded by one (Wfh-sm3) of the isolated clones preferentially degraded 6-kestotriose and possessed minor hydrolase activity to 1-kestotriose and 1,1-kestotetraose. Moreover, Wfh-sm3m hydrolyzed almost all graminans that accumulated in hardened wheat tissues. Wfh-sm3 transcripts increased in wheat leaf tissues inoculated with snow mold and incubated under snow cover. These results suggest that Wfh-sm3 encodes a 6-FEH with minor 1-FEH activity and is associated with degradation of fructans in wheat leaf tissues during inoculation and incubation under snow cover. PMID- 21983140 TI - Acquired digital arteriovenous malformation: clinical, dermoscopy, ultrasound and histological study. PMID- 21983141 TI - Cationic distribution and spin canting in CoFe2O4 nanoparticles. AB - CoFe(2)O(4) nanoparticles (D(NPD) ~6 nm), prepared by a thermal decomposition technique, have been investigated through the combined use of dc magnetization measurements, neutron diffraction, and (57)Fe Mossbauer spectrometry under high applied magnetic field. Despite the small particle size, the value of saturation magnetization at 300 K (M(s) = 70 A m(2) kg(-1)) and at 5 K (M(s) = 100 A m(2) kg(-1)) are rather close to the bulk values, making the samples prepared with this method attractive for biomedical applications. Neutron diffraction measurements indicate the typical ferrimagnetic structure of the ferrites, showing an inversion degree (gamma(NPD) = 0.74) that is in very good agreement with cationic distribution established from low temperature (10 K) Mossbauer measurements in high magnetic field (gamma(moss) = 0.76). In addition, the in-field Mossbauer spectrum shows the presence of a non-collinear spin structure in both A and B sublattices. The results allow us to explain the high value of saturation magnetization and provide a better insight into the complex interplay between cationic distribution and magnetic disorder in ferrimagnetic nanoparticles. PMID- 21983144 TI - Trade-off of energy metabolites as well as body color phenotypes for starvation and desiccation resistance in montane populations of Drosophila melanogaster. AB - Storage of energy metabolites has been investigated in different sets of laboratory selected desiccation or starvation resistant lines but few studies have examined such changes in wild-caught populations of Drosophila melanogaster. In contrast to parallel selection of desiccation and starvation tolerance under laboratory selection experiments, opposite clines were observed in wild populations of D. melanogaster. If resistance to desiccation and starvation occurs in opposite directions under field conditions, we may expect a trade-off for energy metabolites but such correlated changes are largely unknown. We tested whether there is a trade-off for storage as well as actual utilization of carbohydrates (trehalose and glycogen), lipids and proteins in D. melanogaster populations collected from different altitudes (512-2500 m). For desiccation resistance, darker flies (>50% body melanization) store more body water content and endure greater loss of water (higher dehydration tolerance) as compared to lighter flies (<30% body melanization). Based on within population analysis, we found evidence for coadapted phenotypes i.e. darker flies store and actually utilize more carbohydrates to confer greater desiccation resistance. In contrast, higher starvation resistance in lighter flies is associated with storage and actual utilization of greater lipid amount. However, darker and lighter flies did not vary in the rate of utilization of carbohydrates under desiccation stress; and of lipids under starvation stress. Thus, we did not find support for the hypothesis that a lower rate of utilization of energy metabolites may contribute to greater stress resistance. Further, for increased desiccation resistance of darker flies, about two-third of total energy budget is provided by carbohydrates. By contrast, lighter flies derive about 66% of total energy content from lipids which sustain higher starvation tolerance. Our results support evolutionary trade-off for storage as well as utilization of energy metabolites for desiccation versus starvation resistance in D. melanogaster. PMID- 21983143 TI - MRSI correlates of cognitive-behavioral therapy in pediatric obsessive-compulsive disorder. AB - BACKGROUND: The brain mechanisms of cognitive-behavioral therapy (CBT), a highly effective treatment for pediatric obsessive-compulsive disorder (OCD), are unknown. Neuroimaging in adult OCD indicates that CBT is associated with metabolic changes in striatum, thalamus, and anterior cingulate cortex. We therefore probed putative metabolic effects of CBT on these brain structures in pediatric OCD using proton magnetic resonance spectroscopic imaging (1H MRSI). METHOD: Five unmedicated OCD patients (4 ?, 13.5+/-2.8) and 9 healthy controls (7 ?, 13.0+/-2.5) underwent MRSI (1.5 T, repetition-time/echo-time=1500/30 ms) of bilateral putamen, thalamus and pregenual anterior cingulate cortex (pACC). Patients were rescanned after 12 weeks of exposure-based CBT. The Children's Yale Brown Obsessive-Compulsive Scale (CY-BOCS) of OCD symptoms was administered before and after CBT. RESULTS: Four of 5 patients responded to CBT (mean 32.8% CY BOCS reduction). Multiple metabolite effects emerged. Pre-CBT, N-acetyl aspartate+N-acetyl-aspartyl-glutamate (tNAA) in left pregenual anterior cingulate cortex (pACC) was 55.5% higher in patients than controls. Post-CBT, tNAA (15.0%) and Cr (23.9%) in left pACC decreased and choline compounds (Cho) in right thalamus increased (10.6%) in all 5 patients. In left thalamus, lower pre-CBT tNAA, glutamate+glutamine (Glx), and myo-inositol (mI) predicted greater post-CBT drop in CY-BOCS (r=0.98) and CY-BOCS decrease correlated with increased Cho. CONCLUSIONS: Interpretations are offered in terms of the Glutamatergic Hypothesis of Pediatric OCD. Similar to 18FDG-PET in adults, objectively measurable regional MRSI metabolites may indicate pediatric OCD and predict its response to CBT. PMID- 21983142 TI - Planar cell polarity in Drosophila. AB - In all multicellular organisms, epithelial cells are not only polarized along the apical-basal axis, but also within the epithelial plane, giving cells a sense of direction. Planar cell polarity (PCP) signaling regulates establishment of polarity within the plane of an epithelium. The outcomes of PCP signaling are diverse and include the determination of cell fates, the generation of asymmetric but highly aligned structures, such as the stereocilia in the human inner ear or the hairs on a fly wing, or the directional migration of cells during convergence and extension during vertebrate gastrulation. In humans, aberrant PCP signaling can result in severe developmental defects, such as open neural tubes (spina bifida), and can cause cystic kidneys. In this review, we discuss the basic mechanism and more recent findings of PCP signaling focusing on Drosophila melanogaster, the model organism in which most key PCP components were initially identified. PMID- 21983145 TI - Water-soluble vitamin homeostasis in fasting northern elephant seals (Mirounga angustirostris) measured by metabolomics analysis and standard methods. AB - Despite the importance of water-soluble vitamins to metabolism, there is limited knowledge of their serum availability in fasting wildlife. We evaluated changes in water-soluble vitamins in northern elephant seals, a species with an exceptional ability to withstand nutrient deprivation. We used a metabolomics approach to measure vitamins and associated metabolites under extended natural fasts for up to 7 weeks in free-ranging lactating or developing seals. Water soluble vitamins were not detected with this metabolomics platform, but could be measured with standard assays. Concentrations of measured vitamins varied independently, but all were maintained at detectable levels over extended fasts, suggesting that defense of vitamin levels is a component of fasting adaptation in the seals. Metabolomics was not ideal for generating complete vitamin profiles in this species, but gave novel insights into vitamin metabolism by detecting key related metabolites. For example, niacin level reductions in lactating females were associated with significant reductions in precursors suggesting downregulation of the niacin synthetic pathway. The ability to detect individual vitamins using metabolomics may be impacted by the large number of novel compounds detected. Modifications to the analysis platforms and compound detection algorithms used in this study may be required for improving water soluble vitamin detection in this and other novel wildlife systems. PMID- 21983146 TI - Evaluation of sevoflurane as an anesthetic agent for voiding cystourethrography in pediatric patients. AB - BACKGROUND: Sevoflurane anesthetic has recently been administered by anesthesiologists during voiding cystourethrograms in a centre where radiologists are not permitted to deliver pediatric sedation. OBJECTIVE: To determine whether sevoflurane is a satisfactory anesthetic agent for voiding cystourethrography in children. METHODS: Records of children undergoing voiding cystourethrogram while they were under sevoflurane were reviewed for anesthetic adverse effects and diagnostic quality of the cystourethrogram. The occurrence of on-table voiding and post-void residual bladder volume were documented and compared with an age- and sex-matched control group of children undergoing unsedated voiding cystourethrography. The caregivers were surveyed regarding the anesthetic experience. RESULTS: A total of 91 children underwent sevoflurane voiding cystourethrography; there were no adverse cardiorespiratory events. Voiding was observed in 96%, with residual bladder volumes minimal in 38%, moderate in 32%, and large in 28% of anesthetized children, not significantly different from the control group. Vesicoureteral reflux was observed in 53% of examinations under sevoflurane. When children with a previous history of reflux or voiding cystourethrography were excluded in a comparison with age- and sex-matched controls, vesicoureteral reflux was observed in 38% of studies under sevoflurane and in 44% of studies in the control group, P = .69; 85% of caregivers of children with prior unsedated voiding cystourethrography found voiding cystourethrography with sevoflurane easier than without sevoflurane; 89% thought the anesthetic experience reduced their child's anxiety towards medical procedures. CONCLUSION: No adverse events or effects on diagnostic quality of the pediatric voiding cystourethrogram were encountered when using sevoflurane. The majority of surveyed caregivers thought that anesthesia made voiding cystourethrography an easier experience for their child. PMID- 21983147 TI - Lifespan brain activity, beta-amyloid, and Alzheimer's disease. AB - Alzheimer's disease (AD) is the most common cause of progressive cognitive decline and dementia in adults. While the amyloid cascade hypothesis of AD posits an initiating role for the beta-amyloid (Abeta) protein, there is limited understanding of why Abeta is deposited. A growing body of evidence based on in vitro, animal studies and human imaging work suggests that synaptic activity increases Abeta, which is deposited preferentially in multimodal brain regions that show continuous levels of heightened activation and plasticity across the lifespan. Imaging studies of people with genetic predispositions to AD are consistent with these findings, suggesting a mechanism whereby neural efficiency or cognitive reserve may diminish Abeta deposition. The aggregated findings unify observations from cellular and molecular studies with human cognitive neuroscience to reveal potential mechanisms of AD development. PMID- 21983148 TI - What is so special about embodied simulation? AB - Simulation theories of social cognition abound in the literature, but it is often unclear what simulation means and how it works. The discovery of mirror neurons, responding both to action execution and observation, suggested an embodied approach to mental simulation. Over the past few years this approach has been hotly debated and alternative accounts have been proposed. We discuss these accounts and argue that they fail to capture the uniqueness of embodied simulation (ES). ES theory provides a unitary account of basic social cognition, demonstrating that people reuse their own mental states or processes represented with a bodily format in functionally attributing them to others. PMID- 21983149 TI - Does the brain calculate value? AB - How do people choose between options? At one extreme, the 'value-first' view is that the brain computes the value of different options and simply favours options with higher values. An intermediate position, taken by many psychological models of judgment and decision making, is that values are computed but that the resulting choices depend heavily on the context of available options. At the other extreme, the 'comparison-only' view argues that choice depends directly on comparisons, with or even without any intermediate computation of value. In this paper, we place past and current psychological and neuroscientific theories on this spectrum, and review empirical data that have led to an increasing focus on comparison rather than value as the driver of choice. PMID- 21983150 TI - Digital PCR provides absolute quantitation of viral load for an occult RNA virus. AB - Using a multiplexed LNA-based Taqman assay, RT-digital PCR (RT-dPCR) was performed in a prefabricated microfluidic device that monitored absolute viral load in native and immortalized cell lines, overall precision of detection, and the absolute detection limit of an occult RNA virus GB Virus Type C (GBV-C). RT dPCR had on average a 10% lower overall coefficient of variation (CV, a measurement of precision) for viral load testing than RT-qPCR and had a higher overall detection limit, able to quantify as low as three 5'-UTR molecules of GBV C genome. Two commercial high-yield in vitro transcription kits (T7 Ribomax Express by Promega and Ampliscribe T7 Flash by Epicentre) were compared to amplify GBV-C RNA genome with T7-mediated amplification. The Ampliscribe T7 Flash outperformed the T7 Ribomax Express in yield of full-length GBV-C RNA genome. THP 1 cells (a model of monocytic derived cells) were transfected with GBV-C, yielding infectious virions that replicated over a 120h time course and could be infected directly. This study provides the first evidence of GBV-C replication in monocytic derived clonal cells. Thus far, it is the only study using a microfluidic device that measures directly viral load of mammalian RNA virus in a digital format without need for a standard curve. PMID- 21983151 TI - B cells in multiple sclerosis: connecting the dots. AB - Over the past two decades B cells have increasingly moved into the spotlight in multiple sclerosis (MS) research. This interest was fuelled by growing understanding and acceptance of pathological involvement of B cells and antibodies in MS. Data derived from animal models of MS, human histopathological studies, and analyses of B cells in the peripheral blood and cerebrospinal fluid (CSF) have permitted the integration of B cells in our overall picture of MS immunopathogenesis. The as yet strongest direct evidence for a central role of B cells in MS autoimmunity was the demonstration that peripheral B cell depletion leads to a rapid decline of disease-activity in MS. While lending formidable impact to peripheral blood B cells as mediators of disease activity, the effects of anti-CD20 treatment also seemingly challenged the paradigm of a role of antibodies in targeted central nervous system (CNS) myelin destruction. This review shall attempt to provide an overview of our current understanding of B cell and antibody mediated mechanisms relevant to MS. We will include findings from, both, human studies, and animal models to highlight the complexity of B cell function as it pertains to MS. B cells appear to be effective drivers of inflammatory activity in MS by way of a diverse toolset of cellular functions. These functions appear to be closely linked to B cells that can be found in the periphery. However, by serving as the source of antibodies, B cells offer a direct humoral response that may target the CNS and lead to tissue specific destruction. Therefore, B cells participate in MS pathogenesis on both sides of the blood-brain barrier. PMID- 21983153 TI - Risk factors for lower extremity amputation among patients with diabetes in Singapore. AB - BACKGROUND: Among other risk factors, renal disease and ethnicity have been associated with diabetic lower extremity amputation (LEA) in Western populations. However, little is known about risk factors for LEA among Asian patients. OBJECTIVE: The objective was to assess the proportion of hospitalized patients with diabetes who have a LEA among all hospital patients with diabetes mellitus (DM) and to investigate risk factors for diabetic LEA (especially renal disease and ethnicity) using hospital discharge database. METHOD: A retrospective study of hospital discharge database (2004-2009) was performed to identify patients with DM, LEA and renal disease using the International Statistical Classification of Diseases and Related Health Problems, Ninth Revision, Australian Modification codes. RESULTS: Of 44 917 hospitalized patients with DM during the 6 years, 7312 (16.3%) patients had renal disease, and 1457 (3.2%) patients had LEA. DM patients with renal disease had significant higher rates of LEA (7.1%) compared to DM patients without renal disease (2.5%, P < .001). The differences were present for foot (2.7% vs. 1.2%), ankle or leg (2.8% vs. 0.9%), and knee or above amputation (1.6% vs. 0.4%, all P<.001). Malays had the highest rate of diabetic LEA (5.1%), followed by Indians (3.0%), Chinese (3.0%), and others (2.3%, P < .001). In logistic regression analyses, renal disease and ethnicity were significant predictors of diabetic LEA (renal disease: odds ratio 3.2, 95% confidence interval 2.8-3.6; ethnicity: odds ratio, 1.6, Malays vs. Chinese, P < .001; 1.0, Indians vs. Chinese, P = .784) after adjustment for age, gender, and year of discharge. CONCLUSION: DM patients with renal disease and Malay ethnicity had higher rates of LEA in this Asian patient population. Malay patients with DM and diabetic patients with renal disease should be considered as high-risk groups for LEA and therefore screened and monitored systematically. PMID- 21983152 TI - Disparities in diabetes self-management and quality of care in rural versus urban veterans. AB - BACKGROUND: There are distinct geographic differences in diabetes-related morbidity and mortality; however, data regarding self-management and clinical outcomes are limited. This study examined diabetes care among veterans residing in rural versus urban areas. METHODS: A national data set was analyzed based on 10,570 veterans with type 2 diabetes. Residence was determined according to US census-based metropolitan statistical area. Primary outcomes were self-management behaviors (lifestyle and self-monitoring) and quality of care indicators (provider visits, laboratory monitoring and preventive measures). Multivariate analyses were done using STATA v10 to assess the independent effect of veteran residence on each outcome measure and to account for the complex survey design. RESULTS: Among veterans with diabetes, 21.4% were rural residents. Compared to urban veterans, rural veterans had significantly lower education, less annual income and less received diabetes education (P = .002). The final regression model showed that daily foot self-check was the only self-management behavior significantly higher among rural veterans (odds ratio 1.36, 95% confidence interval 1.10-1.70). Provider-based quality of care was not significantly different between groups. CONCLUSIONS: Diabetes self-foot care was significantly better among rural veterans than their urban counterparts, but quality of care was equivalent. This suggests that clinical diabetes care among veterans is uniform; however, greater efforts for patient education and support in diabetes self-management are needed to improve outcomes. PMID- 21983154 TI - A randomized, double-blind noninferiority study of quadrivalent live attenuated influenza vaccine in adults. AB - BACKGROUND: Trivalent seasonal influenza vaccines contain 2 A strains and 1 B strain. B strains of 2 antigenically distinct lineages, Yamagata and Victoria, have been co-circulating annually, and the B strain included in vaccines often has not been a lineage match to the major circulating strain. Thus, a vaccine containing B strains from both lineages could broaden protection against influenza. Quadrivalent live attenuated influenza vaccine (Q/LAIV) is an investigational 4-strain formulation of LAIV that contains 2 A strains, A/H1N1 and A/H3N2, and 2 B strains, 1 from each lineage. METHODS: A randomized, double blind, active-controlled study of Q/LAIV was conducted in 1800 adults aged 18-49 years to compare the immunogenicity and safety of Q/LAIV to trivalent LAIV (T/LAIV). Subjects were randomized 4:1:1 to receive an intranasal dose of Q/LAIV (n=1200) or 1 of 2 matching T/LAIV vaccines, each containing 1 of the B strains included in Q/LAIV (n=600 total). The primary endpoint was the comparison of the post-vaccination strain-specific geometric mean titers (GMT) of hemagglutination inhibition antibody in Q/LAIV recipients to those in T/LAIV recipients, with immunologic noninferiority of Q/LAIV to be demonstrated if the upper bound of the 2-sided 95% confidence interval (CI) for the ratio of the GMTs [T/LAIV divided by Q/LAIV] was <=1.5 for all strains. RESULTS AND CONCLUSION: Q/LAIV met the criteria for noninferiority: the ratios of the GMTs for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria strains were 1.09 (95% CI, 1.01-1.18), 1.05 (95% CI, 0.96-1.14), 1.10 (95% CI, 0.97-1.25), and 0.92 (95% CI, 0.82-1.03), respectively. Solicited symptoms and adverse events were similar in the Q/LAIV and T/LAIV arms. Q/LAIV may confer increased protection against influenza by targeting B strains from both lineages. PMID- 21983156 TI - Assessment of serological evidence for mumps virus infection in vaccinated children. AB - It is estimated that at least one-third of mumps virus infections in non vaccinated individuals are asymptomatic. Little information is available whether this proportion is the same among those vaccinated. We validated a commercial oral fluid mumps IgG-specific Enzyme Immunoassays (EIA) with vaccinated control groups to identify symptomatic and asymptomatic mumps virus infections in vaccinated individuals during a mumps outbreak in The Netherlands. A vaccinated control group was required to define a new cutoff value for the assay, because of the presence of low but significant levels of IgG antibodies in oral fluid as a result of mumps vaccination in the past. With a new cutoff, calculated using receiver operator characteristic analysis, we identified an attack rate of 7-10% compared to 2.7% based on clinical symptoms among vaccinated children. This finding has important implications when studying transmission patterns, strain virulence, as well as mumps vaccine effectiveness to protect from infection rather than disease. PMID- 21983155 TI - Antibody responses and cross protection against lethal influenza A viruses differ between the sexes in C57BL/6 mice. AB - A mouse model was used to determine if protective immunity to influenza A virus infection differs between the sexes. The median lethal dose of H1N1 or H3N2 was lower for naive females than males. After a sublethal, primary infection with H1N1 or H3N2, females and males showed a similar transient morbidity, but females generated more neutralizing and total anti-influenza A virus antibodies. Immunized males and females showed similar protection against secondary challenge with a homologous virus, but males experienced greater morbidity and had higher lung viral titers after infection with a lethal dose of heterologous virus. Females develop stronger humoral immune responses and greater cross protection against heterosubtypic virus challenge. PMID- 21983157 TI - A recombinant Bacille Calmette-Guerin construct expressing the Plasmodium falciparum circumsporozoite protein enhances dendritic cell activation and primes for circumsporozoite-specific memory cells in BALB/c mice. AB - A protective malaria vaccine may induce both high levels of neutralising antibodies and strong T-cell responses. The Plasmodium falciparum circumsporozoite protein (CSp) is a leading pre-erythrocytic vaccine candidate. CSp is a week immunogen per se, but Mycobacterium bovis Bacille Calmette-Guerin (BCG) has excellent adjuvant activity and has been utilized as a vector to deliver heterologous vaccine candidate antigens. It is safe in immunocompetent individuals and inexpensive to produce. We assessed in vitro and in vivo a recombinant BCG-expressing CSp (BCG-CS) as malaria vaccine candidate. Immunisation of BALB/c mice with BCG-CS augmented numbers of dendritic cells (DCs) in draining lymph nodes and in the spleen. The activation markers MHC-class II, CD40, CD80 and CD86 on DCs were significantly upregulated by BCG-CS as compared to wild-type BCG (wt-BCG). In vitro stimulation of bone marrow-derived DCs and macrophages with BCG-CS induced IL-12 and TNF-alpha production. BCG-CS induced higher phagocytic activity in macrophages as compared to wt-BCG. Immunogenicity studies show that BCG-CS induced CS-specific antibodies and IFN gamma-producing memory cells. In conclusion, BCG-CS is highly efficient in activating antigen-presenting cells (APCs) for priming of adaptive immunity. Implications for the rational design of novel vaccines against malaria and TB, the two major devastating poverty-related diseases, are discussed. PMID- 21983158 TI - Pyrrolidine dithiocarbamate attenuates brain Abeta increase and improves long term neurological outcome in rats after transient focal brain ischemia. AB - Evidence suggests an association between brain ischemia and Alzheimer's disease (AD) development. Amyloid plaques consisted of beta-amyloid peptide (Abeta) in the brain are a pathological hallmark of AD. Little is known about how brain ischemia induces AD-like neuropathology. A strategy effective to block such brain changes has not been reported. Here, adult male Sprague-Dawley rats were subjected to a 90-min right middle cerebral artery occlusion (MCAO). Pyrrolidine dithiocarbamate (PDTC) at various doses was given daily via gastric gavage with the first dose given at 10 min after the onset of reperfusion. The MCAO increased Abeta1-42 concentrations in the ischemic brain tissues. PDTC attenuated this increase. PDTC also decreased the ischemia-reduced expression of neprilysin, an Abeta degrading enzyme. Abeta1-42 levels were negatively correlated with neprilysin protein abundance. Brain ischemia decreased the expression of beta amyloid converting enzyme 1, a key enzyme to produce Abeta, and increased the expression of insulin-degrading enzyme, another Abeta degrading enzyme. Animals had impaired learning and memory at 2 months after the MCAO. PDTC attenuated this impairment. PDTC also improved long-term neurological outcomes. Our findings suggest that PDTC improves long-term neurological outcome of rats after transient focal brain ischemia. PDTC reduces ischemia-induced Abeta accumulation, possibly via preserving neprilysin expression. PMID- 21983159 TI - miR-181 regulates GRP78 and influences outcome from cerebral ischemia in vitro and in vivo. AB - MicroRNAs (miRNA) are short (~22nt) single stranded RNAs that downregulate gene expression. Although recent studies indicate extensive miRNA changes in response to ischemic brain injury, there is currently little information on the roles of specific miRNAs in this setting. Heat shock proteins (HSP) of the HSP70 family have been extensively studied for their multiple roles in cellular protection, but there is little information on their regulation by miRNAs. We used bioinformatics to identify miR-181 as a possible regulator of several HSP70 family members. We validated GRP78/BIP as a target by dual luciferase assay. In response to stroke in the mouse we find that miR-181 increases in the core, where cells die, but decreases in the penumbra, where cells survive. Increased levels of miR-181a are associated with decreased GRP78 protein levels, but increased levels of mRNA, implicating translational arrest. We manipulated levels of miR 181a using plasmid overexpression of pri-miR-181ab or mimic to increase, and antagomir or inhibitor to reduce levels. Increased miR-181a exacerbated injury both in vitro and in the mouse stroke model. Conversely, reduced levels were associated with reduced injury and increased GRP78 protein levels. Studies in C6 cells show that if GRP78 levels are maintained miR-181a no longer exerts a toxic effect. These data demonstrate that miR-181 levels change in response to stroke and inversely correlate with levels of GRP78. Importantly, reducing or blocking miR-181a protects the brain from stroke. PMID- 21983161 TI - Mild cystic fibrosis in patients with the rare P5L CFTR mutation. AB - Over 1800 Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) mutations have been identified so far, determining different degrees of CFTR dysfunction and a range of different cystic fibrosis phenotypes. The P5L CFTR mutation is a recently described N-terminus missense variant which may cause defect of protein folding and processing/trafficking, but the functional classification is still unclear. Given the rarity of the mutation, the associated clinical phenotype is still unknown. The aim of our study was to describe the clinical phenotypes in a group of 7 patients with the P5L mutation including 2 adults, 2 adolescents and 3 children. The P5L variant was associated with DeltaF508 in 5 patients and with W1282X in two patients. All patients had positive or borderline sweat test values. All had pancreatic sufficiency, no hepatobiliary disease, no or mild respiratory symptoms and normal lung function. The two adult males were fertile. Most of the patients presented recurrent episodes of dehydration and hypochloronatremia. We conclude that, although it has been speculated that the N-terminus CFTR missense variants may severely affect the behaviour of the CFTR chloride channel, patients with the P5L CFTR mutation, in association with a severe class II mutation, may be asymptomatic or may be affected by mild disease. PMID- 21983160 TI - Identification and engineering of the cytochalasin gene cluster from Aspergillus clavatus NRRL 1. AB - Cytochalasins are a group of fungal secondary metabolites with diverse structures and bioactivities, including cytochalasin E produced by Aspergillus clavatus, which is a potent anti-angiogenic agent. Here, we report the identification and characterization of the cytochalasin gene cluster from A. clavatus NRRL 1. As a producer of cytochalasin E and K, the genome of A. clavatus was analyzed and the ~30 kb ccs gene cluster was identified based on the presence of a polyketide synthase-nonribosomal peptide synthetases (PKS-NRPS) and a putative Baeyer Villiger monooxygenase (BVMO). Deletion of the central PKS-NRPS gene, ccsA, abolished the production of cytochalasin E and K, confirming the association between the natural products and the gene cluster. Based on bioinformatic analysis, a putative biosynthetic pathway is proposed. Furthermore, overexpression of the pathway specific regulator ccsR elevated the titer of cytochalasin E from 25mg/L to 175 mg/L. Our results not only shed light on the biosynthesis of cytochalasins, but also provided genetic tools for increasing and engineering the production. PMID- 21983162 TI - Unfavorable clinical implications of circulating CD44+ lymphocytes in patients with nasopharyngeal carcinoma undergoing radiochemotherapy. AB - BACKGROUND: To evaluate the use of cellular immunity parameters as predictors of therapy response. METHODS: Circulating lymphocytes were measued by flow cytometry in 94 nasopharyngeal carcinoma (NPC) patients following radiochemotherapy. RESULTS: Significantly decreased percentage of CD3(+), CD4(+), and CD8(+) lymphocytes, significantly increased proportion of CD44(+), CD25(+), NK lymphocytes, and an increased CD4(+)/CD8(+) ratio were indicated in NPC patients as compared with healthy controls. Circulating CD44(+) lymphocytes in both the N2/N3 and III/IV groups were significantly increased as compared to the N0/N1 and I/II groups, respectively (P<0.05). A significant decrease in CD19(+) lymphocytes was observed in the III/IV group as compared with the I/II group (P<0.05). After radiochemotherapy, NPC patients had significantly (P<0.05) decreased percentages of CD4(+), CD44(+), and CD19(+) lymphocytes and a decreased CD4(+)/CD8(+) ratio, whereas the mean percentages of CD8(+) and NK lymphocytes were significantly (P<0.05) increased. However, compared with the pre-radiochemotherapy values, no significant (P>0.05) changes in CD3(+) or CD25(+) lymphocytes were observed in the NPC-treated group. Follow-up analysis indicated significantly lower DFS for patients with high CD44(+) lymphocytes compared to those with low CD44(+) lymphocytes after radiochemotherapy. CONCLUSION: Circulating CD44(+) lymphocytes seems to be a promising criterion to predict survival in NPC patients undergoing radiochemotherapy. PMID- 21983163 TI - Impact of 10 mg rosuvastatin daily or alternate-day on lipid profile and inflammatory markers. AB - BACKGROUND: Statins are commonly administrated daily, while rosuvastatin can be given every other day due to its longer half-lives. We evaluated the potential efficacy of alternate-day dosing of 10mg rosuvastatin compared with daily dosing of 10mg rosuvastatin with regarding to lipid and inflammatory markers in patients with dyslipidemia. METHODS: Thirty-seven patients were randomly divided into the 2 groups: alternate-day group (rosuvastatin 10mg every other day, n=19) and once daily group (rosuvastatin 10mg every day, n=18) for 6 weeks. The primary endpoints of the study were changes of the serum concentrations of low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP) and interleukin-6 (IL 6) following 6-week rosuvastatin therapy. RESULTS: Baseline characteristics of the 2 groups were well balanced. LDL-C decreased by 37.5% after the once-daily dosing period and by 36.9% after alternate-day dosing period (p>0.05). Both dosing regimens provided similar improvement in high-density lipoprotein cholesterol and triglyceride. And also, both dosing regimens significantly decreased serum concentrations of CRP, which had an 18.3% reduction in once-daily dosing and a 16.7% reduction in alternate-day dosing of rosuvastatin (p>0.05). Moreover, the pattern of plasma IL-6 concentrations was also similar between the two groups (p>0.05). CONCLUSIONS: Alternate-day dosing of rosuvastatin could be effective comparable with once-daily dosing of rosuvastatin in Chinese patients in improving not only lipid profile but also inflammatory markers, which may provide some cost savings and increase the compliance of patients. PMID- 21983164 TI - 3-epi-25 hydroxyvitamin D concentrations are not correlated with age in a cohort of infants and adults. AB - BACKGROUND: The implementation of mass spectrometry to measure serum 25 hydroxyvitamin D [25(OH)D] concentrations has led to concerns regarding the measurement and reporting of the C3-epimer of 25-hydroxyvitamin D(3) [3-epi 25(OH)D(3)], for which there is a near-total lack of data regarding its clinical significance. METHODS: We developed a chromatographic method to resolve (>90%) 3 epi-25(OH)D(3) from 25(OH)D(3) using a pentafluorophenyl propyl chromatographic column. Using LC-MS/MS, we determined the serum concentrations of 25(OH)D(3) and 3-epi-25(OH)D(3) in 626 patients aged 3 days to 94 years undergoing routine vitamin D testing. RESULTS: Comparison between DiaSorin RIA and the new LC-MS/MS method for total 25(OH)D had acceptable agreement. Our data indicate an increase in 25(OH)D(3) rather than a reduction in epimer concentration. An average of 3.3 ng/ml of 3-epi-25(OH)D(3) was detected in adolescents and adults. Inclusion of 3 epi-25(OH)D(3) in the total 25(OH)D(3) concentration resulted in 9% (<1 year) and 3% (1 to 94 years) potential misclassification of patients as vitamin D sufficient. CONCLUSIONS: The new LC-MS/MS method is capable of chromatographically separating 25(OH)D(3) and 3-epi-25(OH)D(3). It was used to confirm that the contribution of 3-epi-25OHD(3) to total 25OHD(3) concentrations decreases with age in infants and is detectable in adults. PMID- 21983165 TI - Increased circulating plasma lysophosphatidic acid in patients with acute coronary syndrome. AB - BACKGROUND: The platelet activator lysophosphatidic acid (LPA) has recently been identified as an ingredient in oxidized LDL and it has been isolated from atherosclerotic plaques. The lysophospholipase D activity of autotaxin produces LPA extracellularly from lysophosphatidylcholine (LPC). The present study determines whether circulating LPA is associated with acute coronary syndrome (ACS). METHODS: We enrolled 141 consecutive patients (age, 62.6+/-3.8 y; male, 69.2%) with ACS (n=38), stable angina pectoris (SAP; n=72) or angiographically normal coronary arteries (NCA; n=31). The relationships between LPA and other established biomarkers were examined. Concentrations of plasma LPA were determined using an enzymatic assay. RESULTS: Concentrations of LPA significantly correlated with LPC (r=0.549), autotaxin (r=0.370) and LDL-C (r=0.307) (all p<0.01). Lysophosphatidic acid concentrations were significantly higher in patients with ACS than with SAP and NCA (p<0.01), but did not significantly differ between patients with SAP and NCA. Multivariate logistic regression analyses revealed that the highest LPA tertile was independently associated with ACS (odds ratio 1.99, 95% CI: 1.18-3.39, p=0.02). CONCLUSIONS: The present study demonstrated that increased circulating plasma LPA concentrations are significantly associated with ACS. PMID- 21983166 TI - Optimization of petroleum refinery effluent treatment in a UASB reactor using response surface methodology. AB - An upflow anaerobic sludge blanket (UASB) bioreactor was successfully used for the treatment of petroleum refinery effluent. Before optimization, chemical oxygen demand (COD) removal was 81% at a constant organic loading rate (OLR) of 0.4 kg/m(3) d and a hydraulic retention time (HRT) of 48 h. The rate of biogas production was 559 mL/h at an HRT of 40 h and an influent COD of 1000 mg/L. Response surface methodology (RSM) was applied to predict the behaviors of influent COD, upflow velocity (V(up)) and HRT in the bioreactor. RSM showed that the best models for COD removal and biogas production rate were the reduced quadratic and cubic models, respectively. The optimum region, identified based on two critical responses, was an influent COD of 630 mg/L, a V(up) of 0.27 m/h, and an HRT of 21.4 h. This resulted in a 76.3% COD removal efficiency and a 0.25 L biogas/L feed d biogas production rate. PMID- 21983167 TI - Leaching properties of slag generated by a gasification/vitrification unit: the role of pH, particle size, contact time and cooling method used. AB - The environmental impact from the operation of thermal waste treatment facilities mainly originates from the air emissions, as well as the generated solid residues. The objective of this paper is to examine the slag residue generated by a demonstration plasma gasification/vitrification unit and investigate the composition, the leaching properties of the slag under different conditions, as well as the role of the cooling method used. The influence of pH, particle size and contact time on the leachability of heavy metals are discussed. The main outcome is that the vitrified slag is characterized as inert and stable and can be safely disposed at landfills or used in the construction sector. Finally, the water-cooled slag showed better resistance in relation to heavy metal leachability compared to the air-cooled slag. PMID- 21983168 TI - Use of gamma-hexachlorocyclohexane as a terminal electron acceptor by an anaerobic enrichment culture. AB - The use of gamma-hexachlorocyclohexane (HCH) as a terminal electron acceptor via organohalide respiration was demonstrated for the first time with an enrichment culture grown in a sulfate-free HEPES-buffered anaerobic mineral salts medium. The enrichment culture was initially developed with soil and groundwater from an industrial site contaminated with HCH isomers, chlorinated benzenes, and chlorinated ethenes. When hydrogen served as the electron donor, 79-90% of the electron equivalents from hydrogen were used by the enrichment culture for reductive dechlorination of the gamma-HCH, which was provided at a saturation concentration of approximately 10 mg/L. Benzene and chlorobenzene were the only volatile transformation products detected, accounting for 25% and 75% of the gamma-HCH consumed (on a molar basis), respectively. The enrichment culture remained active with only hydrogen as the electron donor and gamma-HCH as the electron acceptor through several transfers to fresh mineral salts medium for more than one year. Addition of vancomycin to the culture significantly slowed the rate of gamma-HCH dechlorination, suggesting that a Gram-positive organism is responsible for the reduction of gamma-HCH. Analysis of the gamma-HCH dechlorinating enrichment culture did not detect any known chlororespiring genera, including Dehalobacter. In bicarbonate-buffered medium, reductive dechlorination of gamma-HCH was accompanied by significant levels of acetogenesis as well as methanogenesis. PMID- 21983169 TI - Biosorption of cadmium by Brevundimonas sp. ZF12 strain, a novel biosorbent isolated from hot-spring waters in high background radiation areas. AB - The aim of this study is to screen cadmium biosorbing bacterial strains isolated from soils and hot-springs containing high concentrations of radium ((226)Ra) in Ramsar using a batch system. Brevundimonas sp. ZF12 strain isolated from the water with high (226)Ra content caused 50% removal of cadmium at a concentration level of 250 ppm. The biosorption equilibrium data are fitted well by the Langmuir adsorption isotherm and kinetic studies indicated that the biosorption follows pseudo second-order model. The effect of different physico-chemical parameters like biomass concentration, pH, cadmium concentration, temperature and contact time on cadmium sorption was also investigated using FTIR, SEM and XRD analytical techniques. A high desorption efficiency (above 90%) was obtained using a pH range of 2.0-4.0. Reusability of the biomass was examined under consecutive biosorption-desorption cycles repeated thrice. In conclusion, Brevundimonas sp. ZF12 is proposed as an excellent cadmium biosorbent that may have important applications in Cd removal from wastewaters. PMID- 21983170 TI - Photocatalytic degradation kinetics and mechanism of antivirus drug-lamivudine in TiO2 dispersion. AB - Photocatalytic degradation kinetics of antivirus drug-lamivudine in aqueous TiO(2) dispersions was systematically optimized by both single-variable-at-a-time and central composite design based on the response surface methodology. Three variables, TiO(2) content, initial pH and lamivudine concentration, were selected to determine the dependence of degradation efficiencies of lamivudine on independent variables. Response surface methodology modeling results indicated that degradation efficiencies of lamivudine were highly affected by TiO(2) content and initial lamivudine concentration. The highest degradation efficiency was achieved at suitable amount of TiO(2) and with maintaining initial lamivudine concentration to a minimum. In addition, the contribution experiments of various primary reactive species produced during the photocatalysis were investigated with the addition of different scavengers and found that hydroxyl radicals was the major reactive species involved in lamivudine degradation in aqueous TiO(2). Six degradation intermediates were identified using HPLC/MS/MS, and photocatalytic degradation mechanism of lamivudine was proposed by utilizing collective information from both experimental results of HPLC/MS/MS, ion chromatography as well as total organic carbon and theoretical data of frontier electron densities and point charges. PMID- 21983171 TI - [(11)C]-DASB microPET imaging in the aged rat: frontal and meso-thalamic increases in serotonin transporter binding. AB - Whereas molecular imaging studies in the aging human brain have predominantly demonstrated reductions in serotonin transporter (5-HTT) availability, the majority of the rodent studies, using autoradiographic methods, report increases in neural 5-HTT levels with age. To our knowledge, however, no previous rodent studies have assessed this topic in vivo, and therefore it remains unclear whether this discrepancy arises from methodological or inter-species differences. We performed an [(11)C]-DASB microPET study to evaluate the effects of aging on 5 HTT availability in the rat brain. To generate binding potential estimates, quantitative tracer kinetic modeling was applied using the simplified reference tissue model. A global increase in whole-brain [(11)C]-DASB binding potential was observed in the aged rats in comparison to the control group. More specifically, regional analyses revealed a highly significant increase in 5-HTT binding in the medial frontal cortex, and more modest increments in the midbrain/thalamus. Our results suggest that the frontal cortex represents a site of robust age-related alterations in the rat serotonergic system, and stress the need for further research assessing this topic in the human frontal cortex. Moreover, these findings suggest that the reported discrepancies between rodent and human data may reflect a divergence in the aging processes affecting human and rat serotonergic terminals. PMID- 21983173 TI - Androgen and androgen metabolite levels in serum and urine of East African chimpanzees (Pan troglodytes schweinfurthii): comparison of EIA and LC-MS analyses. AB - The primary male androgen testosterone (T) is often used as an endocrinological marker to investigate androgen-behaviour interactions in males. In chimpanzees and bonobos, studies investigating the relationship between T levels and dominance rank or aggressive behaviour have revealed contradictory results. The immunoassays used in these studies were originally developed for the measurement of steroids in serum. Their application to non-invasively collected samples, however, can lead to methodological problems due to cross-reacting metabolites, which might occur in urine or faeces but not in blood. The overall aim of this study, therefore, is to clarify whether a T enzyme immunoassay (EIA) is an applicable method to monitor testicular function in adult male chimpanzees. To estimate the impact of cross-reacting androgens on the used T EIA, we compared the results of an EIA measurement with a set of androgen metabolite levels measured by LC-MS. In urine from male chimpanzees, cross-reactivities appear to exist mainly with T and its exclusive metabolites, 5alpha-dihydrotestosterone (5alpha-DHT) and 5alpha-androstanediol (androstanediol). Both urinary and serum T levels of male chimpanzees were significantly higher than female T levels when measured with the T EIA, indicating a reliable measurement of testicular androgens and their exclusive metabolites with the used EIA. In urine from female chimpanzees, the comparison between LC-MS and T EIA results indicated a higher impact of cross-reactions with adrenal androgen metabolites. Therefore, the investigation of urinary T levels in female chimpanzees with a T EIA seems to be problematic. Overall our results show that a T EIA can be a reliable method to monitor testicular function in male chimpanzee urine and that LC-MS is a valuable tool for the validation of immunoassays. PMID- 21983172 TI - UBR1 promotes protein kinase quality control and sensitizes cells to Hsp90 inhibition. AB - UBR1 and UBR2 are N-recognin ubiquitin ligases that function in the N-end rule degradation pathway. In yeast, the UBR1 homologue also functions by N-end rule independent means to promote degradation of misfolded proteins generated by treatment of cells with geldanamycin, a small molecule inhibitor of Hsp90. Based on these studies we examined the role of mammalian UBR1 and UBR2 in the degradation of protein kinase clients upon Hsp90 inhibition. Our findings show that protein kinase clients Akt and Cdk4 are still degraded in mouse Ubr1(-)/(-) cells treated with geldanamycin, but that their levels recover much more rapidly than is found in wild type cells. These findings correlate with increased induction of Hsp90 expression in the Ubr1(-)/(-) cells compared with wild type cells. We also observed a reduction of UBR1 protein levels in geldanamycin treated mouse embryonic fibroblasts and human breast cancer cells, suggesting that UBR1 is an Hsp90 client. Further studies revealed a functional overlap between UBR1 and the quality control ubiquitin ligase, CHIP. Our findings show that UBR1 function is conserved in controlling the levels of Hsp90-dependent protein kinases upon geldanamycin treatment, and suggest that it plays a role in determining the sensitivity of cancer cells to the chemotherapeutic effects of Hsp90 inhibitors. PMID- 21983174 TI - Effect of electron doping on the magnetic correlations in the bilayered brownmillerite compound Ca(2.5-x)La(x)Sr(0.5)GaMn2O8: a neutron diffraction study. AB - The effect of electron doping on the magnetic properties of the brownmillerite type bilayered compounds has been investigated by neutron powder diffraction in La substituted Ca(2.5-x)La(x)Sr(0.5)GaMn(2)O(8) compounds (x = 0.05 and 0.1), in comparison with the undoped compound (x = 0). In all compounds, a long-range three-dimensional collinear antiferromagnetic (AFM) structure is found below the Neel temperature T(N) of the respective compound, whereas, well above T(N), three dimensional short-range magnetic ordering is observed. In the intermediate temperature range just above T(N), a strong effect of electron doping (La substitution) on the magnetic correlations has been observed. Here, a short-range AFM correlation with a possible dimensionality of three has been found for substituted compounds (x = 0.05 and 0.1) as compared to the reported two dimensional long-range AFM ordering in the parent compound. With increasing electron doping, a decrease in T(N) is also observed. The short-range magnetic correlations set in over a large temperature range above T(N). A magnetic phase diagram in the x-T plane is proposed from these results. PMID- 21983175 TI - Loss of MAGT1 abrogates the Mg2+ flux required for T cell signaling and leads to a novel human primary immunodeficiency. AB - Although Mg(2+) has a well-recognized role as an essential cofactor for all ATP binding enzymes, its role as a signaling ion, like Ca(2+), has been controversial. A requirement for Mg(2+)for optimal T lymphocyte stimulation was demonstrated more than 30 years ago, but the mechanism of its synergistic effect with Ca(2+)in T cell activation remains elusive. Here, we summarize our recent discovery of a signaling role for Mg(2+)in the T cell antigen receptor (TCR) signaling pathway from the study of a novel primary immunodeficiency, now named X linked immunodeficiency with Mg(2+)defect, EBV infection and neoplasia (XMEN). XMEN patients were found to have a deficiency in magnesium transporter 1 (MAGT1), an Mg(2+)-specific transporter, which leads to the absence of a TCR-stimulated Mg(2+)flux and an attenuation of T cell activation. We further showed that this Mg(2+)flux is required proximally for the temporal orchestration of phospholipase C-gamma1 (PLCgamma1) activation. Thus, our study not only provides a second messenger role for Mg(2+)to explain its synergism with calcium in T cell signaling, it also identifies a potential extracellular therapeutic target for T cell-specific immunomodulation. PMID- 21983176 TI - Treatment of polycythemia vera with imatinib mesylate. AB - We treated 37 patients with polycythemia vera with imatinib mesylate (IM). The overall response rate was 49%. Thirty percent had a complete response, and 19%, a partial response. Thirty-one patients were treated for >120 days. Frequent side effects included nausea, diarrhea, edema, and skin rash. Whereas IM was effective in controlling erythropoiesis and reducing spleen size it was ineffective in controlling thrombocytosis. Normocellular marrow developed in 4 patients who had a complete response. Progression to overt myelofibrosis occurred in 3. Nevertheless, 6 patients have had a sustained complete response while on IM for >6 years. These patients were young, had high phlebotomy requirements, and only slightly elevated platelet counts. Therefore, we believe there may be a role for IM in patients with these characteristics whose disease cannot be controlled by, or as an alternative to, other myelosuppressive treatments. PMID- 21983177 TI - Jumping translocations of 3q21 in an acute monocytic leukemia (M5) patient reveal mechanisms of multistage telomere shortening in pathogenesis of AML. PMID- 21983178 TI - Lipid peroxidation modifies the picture of membranes from the "Fluid Mosaic Model" to the "Lipid Whisker Model". AB - The "Fluid Mosaic Model", described by Singer and Nicolson, explain both how a cell membrane preserves a critical barrier function while it concomitantly facilitates rapid lateral diffusion of proteins and lipids within the planar membrane surface. However, the lipid components of biological plasma membranes are not regularly distributed. They are thought to contain "rafts" - nano-domains enriched in sphingolipids and cholesterol that are distinct from surrounding membranes of unsaturated phospholipids. Cholesterol and fatty acids adjust the transport and diffusion of molecular oxygen in membranes. The presence of cholesterol and saturated phospholipids decreases oxygen permeability across the membrane. Alpha-tocopherol, the main antioxidant in biological membranes, partition into domains that are enriched in polyunsaturated phospholipids increasing the concentration of the vitamin in the place where it is most required. On the basis of these observations, it is possible to assume that non raft domains enriched in phospholipids containing PUFAs and vitamin E will be more accessible by molecular oxygen than lipid raft domains enriched in sphingolipids and cholesterol. This situation will render some nano-domains more sensitive to lipid peroxidation than others. Phospholipid oxidation products are very likely to alter the properties of biological membranes, because their polarity and shape may differ considerably from the structures of their parent molecules. Addition of a polar oxygen atom to several peroxidized fatty acids reorients the acyl chain whereby it no longer remains buried within the membrane interior, but rather projects into the aqueous environment "Lipid Whisker Model". This exceptional conformational change facilitates direct physical access of the oxidized fatty acid moiety to cell surface scavenger receptors. PMID- 21983180 TI - Phasic deactivation of the medial temporal lobe enables working memory processing under stress. AB - Demanding cognitive tasks are sometimes carried out under stressful conditions. Several studies indicate that whereas severe stress impairs performance, moderate stress can enhance cognitive performance. In this study, we investigated how moderate stress influences the neural systems supporting working memory. We embedded an N-back working memory task in a moderately stressful context, as indicated by our physiological stress measures, and probed phasic and tonic human brain activity using two fMRI-techniques: conventional blood oxygen level dependent fMRI and arterial spin labeling (ASL). The results showed that the stress induction, as compared to the neutral control condition, led to slightly faster reaction times without changes in accuracy. In general, working memory processing was associated with increased activity in a frontoparietal network and reduced activity in the medial temporal lobe (MTL). The stress induction led to enhanced reduction of phasic MTL responses, specifically the hippocampus and amygdala. In addition, ASL showed that stress increased tonic amygdala activity, while tonic hippocampal activity was unaffected. These findings suggest that the influence of stress on MTL deactivation during working memory processing is task related rather than a general consequence of the stressful state. The temporal suspension of hippocampal processing in favor of more task relevant processes may allow subjects to maintain normal performance levels under moderate stress. PMID- 21983179 TI - Silencing of the Wnt transcription factor TCF4 sensitizes colorectal cancer cells to (chemo-) radiotherapy. AB - A considerable percentage of rectal cancers are resistant to standard preoperative chemoradiotherapy. Because patients with a priori-resistant tumors do not benefit from multimodal treatment, understanding and overcoming this resistance remains of utmost clinical importance. We recently reported overexpression of the Wnt transcription factor TCF4, also known as TCF7L2, in rectal cancers that were resistant to 5-fluorouracil-based chemoradiotherapy. Because Wnt signaling has not been associated with treatment response, we aimed to investigate whether TCF4 mediates chemoradioresistance. RNA interference mediated silencing of TCF4 was employed in three colorectal cancer (CRC) cell lines, and sensitivity to (chemo-) radiotherapy was assessed using a standard colony formation assay. Silencing of TCF4 caused a significant sensitization of CRC cells to clinically relevant doses of X-rays. This effect was restricted to tumor cells with high T cell factor (TCF) reporter activity, presumably in a beta catenin-independent manner. Radiosensitization was the consequence of (i) a transcriptional deregulation of Wnt/TCF4 target genes, (ii) a silencing-induced G(2)/M phase arrest, (iii) an impaired ability to adequately halt cell cycle progression after radiation and (iv) a compromised DNA double strand break repair as assessed by gammaH2AX staining. Taken together, our results indicate a novel mechanism through which the Wnt transcription factor TCF4 mediates chemoradioresistance. Moreover, they suggest that TCF4 is a promising molecular target to sensitize resistant tumor cells to (chemo-) radiotherapy. PMID- 21983182 TI - Imitation and observational learning of hand actions: prefrontal involvement and connectivity. AB - The first aim of this event-related fMRI study was to identify the neural circuits involved in imitation learning. We used a rapid imitation task where participants directly imitated pictures of guitar chords. The results provide clear evidence for the involvement of dorsolateral prefrontal cortex, as well as the fronto-parietal mirror circuit (FPMC) during action imitation when the requirements for working memory are low. Connectivity analyses further indicated a robust connectivity between left prefrontal cortex and the components of the FPMC bilaterally. We conclude that a mechanism of automatic perception-action matching alone is insufficient to account for imitation learning. Rather, the motor representation of an observed, complex action, as provided by the FPMC, only serves as the 'raw material' for higher-order supervisory and monitoring operations associated with the prefrontal cortex. The second aim of this study was to assess whether these neural circuits are also recruited during observational practice (OP, without motor execution), or only during physical practice (PP). Whereas prefrontal cortex was not consistently activated in action observation across all participants, prefrontal activation intensities did predict the behavioural practice effects, thus indicating a crucial role of prefrontal cortex also in OP. In addition, whilst OP and PP produced similar activation intensities in the FPMC when assessed during action observation, during imitative execution, the practice-related activation decreases were significantly more pronounced for PP than for OP. This dissociation indicates a lack of execution-related resources in observationally practised actions. More specifically, we found neural efficiency effects in the right motor cingulate basal ganglia circuit and the FPMC that were only observed after PP but not after OP. Finally, we confirmed that practice generally induced activation decreases in the FPMC during both action observation and imitation sessions and outline a framework explaining the discrepant findings in the literature. PMID- 21983181 TI - Spatial attention boosts short-latency neural responses in human visual cortex. AB - In a previous study of visual-spatial attention, Martinez et al. (2007) replicated the well-known finding that stimuli at attended locations elicit enlarged early components in the averaged event-related potential (ERP), which were localized to extrastriate visual cortex. The mechanisms that underlie these attention-related ERP modulations in the latency range of 80-200 ms, however, remain unclear. The main question is whether attention produces increased ERP amplitudes in time-domain averages by augmenting stimulus-triggered neural activity, or alternatively, by increasing the phase-locking of ongoing EEG oscillations to the attended stimuli. We compared these alternative mechanisms using Morlet wavelet decompositions of event-related EEG changes. By analyzing single-trial spectral amplitudes in the theta (4-8 Hz) and alpha (8-12 Hz) bands, which were the dominant frequencies of the early ERP components, it was found that stimuli at attended locations elicited enhanced neural responses in the theta band in the P1 (88-120 ms) and N1 (148-184 ms) latency ranges that were additive with the ongoing EEG. In the alpha band there was evidence for both increased additive neural activity and increased phase-synchronization of the EEG following attended stimuli, but systematic correlations between pre- and post stimulus alpha activity were more consistent with an additive mechanism. These findings provide the strongest evidence to date in humans that short-latency neural activity elicited by stimuli within the spotlight of spatial attention is boosted or amplified at early stages of processing in extrastriate visual cortex. PMID- 21983183 TI - N-acetylaspartate concentration in corpus callosum is positively correlated with intelligence in adolescents. AB - The corpus callosum is the largest white matter bundle in the brain and integrates inter-hemispheric cortices during sensory-motor and high-order cognitive processes. The aim of the present study was to investigate the associations between the metabolite concentrations in the corpus callosum and intelligence among adolescents. Thirty male adolescents aged between 14 and 16 years were included into the study. We measured the intelligence quotient (IQ) scores of the subjects by using the Wechsler Intelligence Scale for Children Revised (verbal, performance and full-scale IQ) test. We used proton MR spectroscopy to measure the absolute concentrations of N-acetylasparate (NAA), creatine (Cr) and choline (Cho) in the genu, midbody and isthmus/splenium regions of the corpus callosum. We also measured the whole brain parenchymal size and used it as a confounding factor in the statistical analyses. We assessed the correlations between neurometabolite concentrations and verbal, performance and full-scale IQ scores. We found a significant positive correlation between the whole brain parenchymal size and the full-scale IQ scores. And, the NAA concentration in the isthmus/splenium region was positively correlated with the performance IQ and full-scale IQ scores. NAA is a marker of neuro/axonal integrity. NAA concentration in white matter is related to the structural and functional integrity of axonal fibers. The positive correlation of the IQ scores with the NAA concentrations in the isthmus/splenium region indicates that more efficient inter-hemispheric data transfer between parieto-occipital cortices may enhance intellectual performance. PMID- 21983184 TI - Quantitative magnetization transfer provides information complementary to grey matter atrophy in Alzheimer's disease brains. AB - Preliminary studies, based on a region-of-interest approach, suggest that quantitative magnetization transfer (qMT), an extension of magnetization transfer imaging, provides complementary information to conventional magnetic resonance imaging (MRI) in the characterisation of Alzheimer's disease (AD). The aim of this study was to extend these findings to the whole brain, using a voxel-wise approach. We recruited 19AD patients and 11 healthy subjects (HS). All subjects had an MRI acquisition at 3.0T including a T(1)-weighted volume, 12 MT-weighted volumes for qMT, and data for computing T(1) and B(1) maps. The T(1)-weighted volumes were processed to yield grey matter (GM) volumetric maps, while the other sequences were used to compute qMT parametric maps of the whole brain. qMT maps were warped to standard space and smoothed, and subsequently compared between groups. Of all the qMT parameters considered, only the forward exchange rate, RM(0)(B), showed significant group differences. These images were therefore retained for the multimodal statistical analysis, designed to locate brain regions of RM(0)(B) differences between AD and HS groups, adjusting for local GM atrophy. Widespread areas of reduced RM(0)(B) were found in AD patients, mainly located in the hippocampus, in the temporal lobe, in the posterior cingulate and in the parietal cortex. These results indicate that, among qMT parameters, RM(0)(B) is the most sensitive to AD pathology. This quantity is altered in the hippocampus of patients with AD (as found by previous works) but also in other brain areas, that PET studies have highlighted as involved with both, reduced glucose metabolism and amyloid beta deposition. RM(0)(B) might reflect, through the measurement of the efficiency of MT exchange, some information with a specific pathological counterpart. Given previous evidence of a strict relationship between RM(0)(B) and intracellular pH, an intriguing speculation is that our findings might reflect metabolic changes related to mitochondrial dysfunction, which has been proposed as a contributor to neurodegeneration in AD. PMID- 21983186 TI - FT-IR, FT-Raman and quantum chemical calculations of (E)-N-carbamimidoyl-4-((3,4 dimethoxybenzylidene) amino) benzenesulfonamide. AB - FT-IR and FT-Raman spectra of (E)-N-carbamimidoyl-4-((3,4-dimethoxybenzylidene) amino) benzenesulfonamide were recorded and analyzed. The vibrational wavenumbers were computed using HF/6-31G*, B3PW91/6-31G* and B3LYP/6-31G* basis. The data obtained from vibrational wavenumber calculations are used to assign vibrational bands obtained experimentally. The results indicate that the B3LYP method is able to provide satisfactory results for predicting vibrational frequencies and structural parameters. The calculated first hyperpolarizability is comparable with the reported values of similar derivatives and is an attractive object for future studies of non-linear optics. The geometrical parameters of the title compound are in agreement with that of similar derivatives. PMID- 21983185 TI - Genetic influences on hippocampal volume differ as a function of testosterone level in middle-aged men. AB - The hippocampus expresses a large number of androgen receptors; therefore, in men it is potentially vulnerable to the gradual age-related decline of testosterone levels. In the present study we sought to elucidate the nature of the relationship between testosterone and hippocampal volume in a sample of middle aged male twins (average age 55.8 years). We found no evidence for a correlation between testosterone level and hippocampal volume, as well as no indication of shared genetic influences. However, a significant moderating effect of testosterone on the genetic and environmental determinants of hippocampal volume was observed. Genetic influences on hippocampal volume increased substantially as a function of increasing testosterone level, while environmental influences either decreased or remained stable. These findings provide evidence for an apparent gene-by-hormone interaction on hippocampal volume. To the best of our knowledge, this is the first study to demonstrate that the heritability of a brain structure in adults may be modified by an endogenous biological factor. PMID- 21983187 TI - Structural insights regarding an insecticidal Talisia esculenta protein and its biotechnological potential for Diatraea saccharalis larval control. AB - Talisin is a seed-storage protein from Talisia esculenta that presents lectin like activities, as well as proteinase-inhibitor properties. The present study aims to provide new in vitro and in silico biochemical information about this protein, shedding some light on its mechanistic inhibitory strategies. A theoretical three-dimensional structure of Talisin bound to trypsin was constructed in order to determine the relative interaction mode. Since the structure of non-competitive inhibition has not been elucidated, Talisin-trypsin docking was carried out using Hex v5.1, since the structure of non-competitive inhibition has not been elucidated. The predicted non-coincidence of the trypsin binding site is completely different from that previously proposed for Kunitz type inhibitors, which demonstrate a substitution of an Arg(64) for the Glu(64) residue. Data, therefore, provide more information regarding the mechanisms of non-competitive plant proteinase inhibitors. Bioassays with Talisin also presented a strong insecticide effect on the larval development of Diatraea saccharalis, demonstrating LD50 and ED50 of ca. 2.0% and 1.5%, respectively. PMID- 21983189 TI - Isolation and characterization of the thrombin-like enzyme from Cryptelytrops albolabris (white-lipped tree viper) venom. AB - A thrombin-like enzyme (termed albolabrase) was isolated in purified form from the venom of Cryptelytrops albolabris (white-lipped tree viper) using high performance anion ion exchange and gel filtration chromatography. The molecular mass of albolabrase was 33.7 kDa as determined by SDS-PAGE and 35.8 kDa as determined by Superose gel filtration chromatography. The N-terminal sequence was determined to be VVGGDECNINE which is homologous to many snake venom thrombin like enzymes. Albolabrase exhibits both arginine ester hydrolase and arginine amidase activities and the enzyme is fastidious towards tripeptide chromogenic anilide substrates. The fibrinogen clotting activity was optimum at 3mg/mL bovine fibrinogen, and showed distinct species differences in the following decreasing order: bovine fibrinogen>dog fibrinogen~human fibrinogen>goat fibrinogen. The enzyme failed to clot both rabbit and cat fibrinogens. Reversed-phase HPLC analysis on the breakdown products of fibrinogenolytic action of albolabrase indicated that the enzyme belongs to the AB class of snake venom thrombin-like enzyme. In the indirect ELISA, IgG anti-albolabrase reacted extensively with most crotalid venoms, except with Tropidolaemus wagleri and Calloselasma rhodostoma venoms. The double sandwich ELISA, however, showed that anti-albolabrase reacted strongly only with venoms from the Trimeresurus complex, and that the results support the proposed new taxonomy changes concerning the Trimeresurus complex. PMID- 21983188 TI - Isolation and molecular characterization of Rem2 isoforms in the rainbow trout (Oncorhynchus mykiss): Tissue and central nervous system expression. AB - REM2 is a member of the REM, RAD, and GEM/KIR (RGK) subfamily of RAS superfamily proteins and plays an important role in brain development and function. In this study, two Rem2 isoforms were isolated from the rainbow trout (Oncorhynchus mykiss). The two genes, designated O. mykiss rem2a and rem2b, both encode 304 amino acid proteins with 61% and 62% identities to zebrafish (Danio rerio) Rem2, respectively, and each with 43% identity to mammalian (human) REM2. To our knowledge, this is the first incidence of Rem2 isoforms in a species that are the result of gene duplication. Both isoforms possessed similar tissue expression profiles with the highest levels in the brain. The rem2a gene has significantly higher expression levels than rem2b in all tissues assayed except the brain and head kidney. In the central nervous system, both isoforms showed similar expression levels with the highest levels occurring in the olfactory bulb, cerebrum, and midbrain, though rem2a expression is significantly higher in the spinal cord. Based on known functional roles of Rem2 in synapse development and stem cell proliferation, the characterization of Rem2 in rainbow trout could shed light on its role in adult vertebrate neurogenesis and brain regeneration. PMID- 21983190 TI - Islet versus pancreas transplantation in Brazil: Defining criteria for pancreas allocation decision. AB - BACKGROUND: Many studies have evaluated whether there are characteristics related to pancreas donors and the islet isolation process that can influence pancreatic islet yield. However, this analysis has not yet been performed in Brazil, one of the world leaders in whole pancreas organ transplantation (WOPT), where pancreas allocation for pancreatic islet transplantation (PIT) has no officially defined criteria. Definition of parameters that would predict the outcome of islet isolation from local pancreas donors would be useful for defining allocation priority in Brazil. OBJECTIVE: To analyze the relationship between multiple donor related and islet isolation variables with the total number of isolated pancreatic islet equivalents (IEQ) in a brazilian sample of pancreas donors. METHODS: Several variables were analyzed in 74 pancreata relative to the outcome of total IEQs obtained at the end of the process. RESULTS: In univariate analysis, body mass index (BMI) (p = 0.003), the presence of fatty infiltrates in the pancreas as observed during harvesting (p = 0.042) and pancreas digestion time (p = 0.046) were identified as variables related to a greater IEQ yield. In a multivariate analysis a statistically significant contribution to the variability of islet yield was found only for the BMI (p = 0.017). A ROC curve defined a BMI = 30 as a cut-off point, with pancreata from donors with BMI > 30 yielding more islets than donors with BMI < 30 (p< 0.001). CONCLUSION: These data reinforce the importance of the donor BMI as a defining parameter for successful islet isolation and establishes this variable as a potential pancreas allocation criterion in Brazil, where there is unequal competition for good quality organs between WOPT and PIT. PMID- 21983191 TI - Validation of a photography-based goniometry method for measuring joint range of motion. AB - BACKGROUND: A critical component of evaluating the outcomes after surgery to restore lost elbow motion is the range of motion (ROM) of the elbow. This study examined if digital photography-based goniometry is as accurate and reliable as clinical goniometry for measuring elbow ROM. MATERIALS AND METHODS: Instrument validity and reliability for photography-based goniometry were evaluated for a consecutive series of 50 elbow contractures by 4 observers with different levels of elbow experience. Goniometric ROM measurements were taken with the elbows in full extension and full flexion directly in the clinic (once) and from digital photographs (twice in a blinded random manner). RESULTS: Instrument validity for photography-based goniometry was extremely high (intraclass correlation coefficient: extension = 0.98, flexion = 0.96). For extension and flexion measurements by the expert surgeon, systematic error was negligible (0 degrees and 1 degrees , respectively). Limits of agreement were 7 degrees (95% confidence interval [CI], 5 degrees to 9 degrees ) and -7 degrees (95% CI, -5 degrees to -9 degrees ) for extension and 8 degrees (95% CI, 6 degrees to 10 degrees ) and -7 degrees (95% CI, -5 degrees to -9 degrees ) for flexion. Interobserver reliability for photography-based goniometry was better than that for clinical goniometry. The least experienced observer's photographic goniometry measurements were closer to the reference measurements than the clinical goniometry measurements. CONCLUSIONS: Photography-based goniometry is accurate and reliable for measuring elbow ROM. The photography-based method relied less on observer expertise than clinical goniometry. This validates an objective measure of patient outcome without requiring doctor-patient contact at a tertiary care center, where most contracture surgeries are done. PMID- 21983192 TI - Sequential ipsilateral glenohumeral arthrodesis and scapulothoracic fusion: a case report. PMID- 21983193 TI - Needs and care of older people living at home in Iceland. AB - BACKGROUND: The Icelandic old-age care system is universal and the official goal is to support older people live independently for as long as possible. The aim of this study is to analyse living conditions and use of formal and informal care of older people in Iceland. METHODS: The results are based on the new study ICEOLD, a telephone survey which included questions on social network, health, activities of daily living, and received support from the community and/or from relatives, neighbours, and friends. RESULTS: Almost half of the sample (47%) receives some kind of care, with 27% of them receiving only informal care, which is understood to mean that informal care is of great importance and families are the main providers of help. For hypothetical future long-term care, older people wish to be cared for in their homes, but those already in need of assistance prefer to be cared for in institutions. DISCUSSION: Caring relatives are the main providers of support to older people in their homes and it is important to provide them with suitable formal support when the care responsibility increases. CONCLUSIONS: As the care system in Iceland is now under reconstruction, the important contribution of informal carers must be recognised and taken into account when planning the care of older people. PMID- 21983194 TI - Socioeconomic status, labour market connection, and self-rated psychological health: the role of social capital and economic stress. AB - AIMS: To investigate the association between socioeconomic status, unemployment and self-rated psychological health, taking economic stress and horizontal trust into account. DESIGN/SETTING/PARTICIPANTS/MEASUREMENTS: The 2008 public health survey in Skane is a cross-sectional postal questionnaire study with a 55% participation rate. A random sample was invited and 28,198 persons aged 18-80 participated. Logistic regression models were used to investigate associations between socioeconomic status by occupation (SES), labour market connection and self-rated psychological health (GHQ12). The multiple regression analyses included age, country of birth, education, economic stress and generalized (horizontal) trust. RESULTS: 13.8% of the men and 18.2% of the women had poor psychological health. Poor psychological health was more common among the young, among those born abroad, among those with lower education, with economic stress, and low horizontal trust. There were no significant differences between the employed and self-employed groups. However, the people who had retired early, the unemployed and those on long-term sick leave had significantly higher odds ratios of poor psychological health than higher non-manual employees throughout the analyses. CONCLUSIONS: There were no differences in psychological health between non-manual employees in higher positions and other employed and self-employed SES groups among men or women. In contrast, the early retired, the unemployed and the category on long-term sick leave had significantly higher odds ratios of poor psychological health among both men and women throughout the multiple analyses. Both economic stress and trust affected this association (i.e., lowered the odds ratios of poor psychological health), but affected by economic stress to a somewhat higher extent. PMID- 21983195 TI - Development of a liquid chromatography-tandem mass spectrometry assay of six antimicrobials in plasma for pharmacokinetic studies in premature infants. AB - This method provides a simple extraction procedure, as well as a validated, sensitive, and specific liquid chromatography-tandem mass spectrometry assay for the simultaneous quantification of ampicillin, piperacillin, tazobactam, meropenem, acyclovir, and metronidazole in human plasma. The method was validated over concentration ranges specific for each compound, with a lower limit of quantification of 50-300 ng/mL and a sample volume of 50 MUL. The method is accurate and precise, with within- and between-day accuracy ranging from 85 to 110% and 92 to 110%, respectively, and within- and between-day precision of 89 111% and 91-109%, respectively. Simplicity, low plasma volume, and high throughput make this method suitable for clinical pharmacokinetic studies in premature infants. PMID- 21983196 TI - Determination of HS270, a new histone deacetylase inhibitor, in rat plasma by LC MS/MS--application to a preclinical pharmacokinetic study. AB - A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) method has been developed and fully validated to determine HS270, a new histone deacetylase (HDAC) inhibitor, in rat plasma using SAHA as the internal standard (IS). After a single step liquid-liquid extraction with acetoacetate, analytes were subjected to LC-MS/MS analysis using positive electro-spray ionization (ESI(+)) under selected reaction monitoring mode (SRM). The chromatographic separation was achieved on a Hypurity C(18) column (50 mm * 2.1 mm, i.d., 5 MUm). The MS/MS detection was conducted by monitoring the fragmentation of m/z 392.3 >100.1 for HS270, m/z 265.1->232.1 for IS. The method had a chromatographic running time of 2.5 min and linear calibration curves over the concentrations of 0.5-1000 ng/mL. The recovery of the method was 70.8-82.5% and the lower limit of quantification (LLOQ) was 0.5 ng/mL. The intra- and inter-batch precisions were less than 15% for all quality control samples at concentrations of 1.0, 100.0, and 750.0 ng/mL. The validated LC-MS/MS method has successfully applied to a HS270 pharmacokinetic study after oral doses of 25, 50, 100, 200 mg/kg, and i.v. dose of 5 mg/kg to rats. PMID- 21983197 TI - Rapid determination of sixteen sulfonylurea herbicides in surface water by solid phase extraction cleanup and ultra-high-pressure liquid chromatography coupled with tandem mass spectrometry. AB - A sensitive and very fast analytical method has been developed for the simultaneous quantification of sixteen sulfonylurea herbicides in surface water. An ultra-high-pressure liquid chromatography coupled with tandem mass spectrometry method with solid phase extraction for sample cleanup has been developed for screening sixteen sulfonylurea herbicides (oxasulfuron, thifensulfuron-methyl, cinosulfuron, metsulfuron methyl, sulfometuron methyl, triasulfuron, rimsulfuron, ethametsulfuron methyl, sulfosulfuron, tribenuron methyl, bensulfuron methyl, iodosulfuron methyl, pyrazosulfuron ethyl, prosulfuron, chlorimuron ethyl, ethoxysulfuron) in water samples simultaneously within 12 min. Water samples were acidified, and the target herbicides were extracted by passing through ProElut C18 extraction cartridges. After drying by nitrogen flow, the cartridges were eluted with elution solvents, and the eluate was then evaporated to dryness, redissolved and analyzed. The mobile phase composed of 0.02% formic acid and acetonitrile using gradient elution. A triple quadrupole mass spectrometer equipped with an electrospray ionization source operated in the positive ion with selective reaction monitoring mode. Each of the analytes in all the samples was monitored using protonated molecule and its two characteristic fragment ions for confirmation. The limits of detection for all analytes were below 1.0 ng/mL, except for sulfosulfuron and prosulfuron, and limits of quantitation were between 1 and 8 ng/mL for this method. Three water types were used for the validation of the method. PMID- 21983198 TI - Simultaneous determination of ipratropium and salbutamol in rat plasma by LC MS/MS and its application to a pharmacokinetic study. AB - A novel, sensitive and specific LC-MS/MS method with silica-based solid-phase extraction was developed for simultaneous determination of ipratropium (IPR) and salbutamol (SAL) in rat plasma. Chromatographic separation was achieved on a Shiseido Capcell Pak CR column (SCX:C(18)=1:4, 150 mm * 2.0 mm, 5 MUm) with a mobile phase consisting of methanol/water (85:15, v/v) containing 20 mmol/L ammonium formate and 0.1% formic acid at a flow rate of 0.3 mL/min. A tandem mass spectrometric detection with an electrospray ionization (ESI) interface was conducted via multiple reaction monitoring (MRM) under positive ionization mode. This method was validated in terms of specificity, linearity, accuracy (within +/ 115.4%), intra- and inter-day precision (<11.4%) over the concentration range of 8-1612 pg/mL for IPR and 50-10,000 pg/mL for SAL. In addition, stability and matrix effects of IPR and SAL in plasma were evaluated. This method has been successfully applied to the pharmacokinetic study of compound ipratropium bromide aerosol mainly containing ipratropium bromide (IB) and salbutamol sulphate (SS) after inhalation in rats. PMID- 21983199 TI - Development and validation of ultra high performance liquid chromatography-mass spectrometry method for LBH589 in mouse plasma and tissues. AB - An ultra high performance liquid chromatography tandem mass spectrometry method (UHPLC-MS/MS) was developed and validated for the quantitation of LBH589, a novel histone deacetylase inhibitor (HDACi), in mouse plasma and tissues (liver, spleen, kidney and lung). Tobramycin was employed as the internal standard. Separation was performed on an Acquity UPLCTM BEH column, with a mobile phase consisting of 10% water (with 0.1% of trifluoroacetic acid) and 90% methanol (with 0.1% trifluoroacetic acid). LBH589 and tobramycin were determined using an electrospray ionization (ESI) interface. Detection was performed on electrospray positive ionization mass spectrometry by multiple reaction monitoring of the transitions of LBH589 at m/z 349.42->157.95 and of tobramycin at 468.2->163. Calibration curves for the UHPLC method (0.0025-1 MUg/mL for plasma and tissue homogenates, equivalent to 0.0357-14.2857 MUg/g for tissue samples) showed a linear range of detector responses (r>0.998). Intra-batch and inter-batch precision expressed as coefficient of variation (CV) ranged from 0.92 to 8.40%. Accuracy expressed as bias, ranged from -2.41 to 2.62%. The lower limit of quantitation (LLOQ) was 0.0025 MUg/mL for both plasma and tissue homogenate samples, equivalent to 0.0357 MUg/g tissue. This method was successfully applied to quantify LBH589 in plasma and tissue samples obtained after the intraperitoneal administration of a single dose of 20 mg/kg of LBH589 in BALB/c mice. PMID- 21983200 TI - Hsp90 in non-mammalian metazoan model systems. AB - The molecular chaperone Hsp90 has been discovered in the heat-shock response of the fruit fly more than 30years ago. Today, it is becoming clear that Hsp90 is in the middle of a regulatory system, participating in the modulation of many essential client proteins and signaling pathways. Exerting these activities, Hsp90 works together with about a dozen of cochaperones. Due to their organismal simplicity and the possibility to influence their genetics on a large scale, many studies have addressed the function of Hsp90 in several multicellular model systems. Defined pathways involving Hsp90 client proteins have been identified in the metazoan model systems of Caenorhabditis elegans, Drosophila melanogaster and the zebrafish Danio rerio. Here, we summarize the functions of Hsp90 during muscle maintenance, development of phenotypic traits and the involvement of Hsp90 in stress responses, all of which were largely uncovered using the model organisms covered in this review. These findings highlight the many specific and general actions of the Hsp90 chaperone machinery. This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90). PMID- 21983201 TI - Phosphorylation of Ind by MAP kinase enhances Ind-dependent transcriptional repression. AB - The Drosophila neuroectoderm is initially subdivided into three longitudinal domains that give rise to columns of neuroblasts. This subdivision is coordinately accomplished by the action of the signaling pathways, Dorsal and Epidermal Growth Factor Receptor (EGFR), in conjunction with the homeodomain proteins, Ventral nervous system defective, Intermediate neuroblasts defective (Ind) and Muscle Segment Homeobox. We previously demonstrated that Ind expression is activated in response to the EGFR pathway. Here we show that EGF signaling subsequently mediates the direct phosphorylation of Ind by MAP kinase, which enhances the capacity of Ind to repress target genes, such as achaete. Specifically, we show that reduced EGF signaling results in diminished repression of achaete in the intermediate column, despite the presence of high levels of Ind protein. We also demonstrate that ectopic activation of MAP kinase results in the lateral expansion of the Ind expression domain with a corresponding reduction in achaete expression. This regulation is also dependent on the co-repressor, Dichaete. Our data indicate that EGF signaling, acting through MAP kinase, impinges on multiple aspects of Ind regulatory activity. While it has been often demonstrated that MAP kinase phosphorylation of transcriptional repressors attenuates their repressor activity, here we provide an example of phosphorylation enhancing repressor activity. PMID- 21983202 TI - Better by the pound: the genetics of birth weight. PMID- 21983203 TI - Use of fresh frozen plasma in children. PMID- 21983204 TI - Advertising influences on young children's food choices and parental influence. AB - OBJECTIVE: To evaluate whether advertising for food influences choices made by children, the strength of these influences, and whether they might be easily undone by parental influences. STUDY DESIGN: Children between 3 and 8 years of age (n=75) were randomized to watch a series of programs with embedded commercials. Some children watched a commercial for a relatively healthy food item, the other children watched a commercial for a less healthy item, both from the same fast-food company. Children were also randomized either to receive parental encouragement to choose the healthy item or to choose whichever item they preferred. RESULTS: Results indicated that children were more likely to choose the advertised item, despite parental input. Parental input only slightly moderated this influence. CONCLUSION: Although advertising impact on children's food choices is moderate in size, it appears resilient to parental efforts to intervene. Food advertisements directed at children may have a small but meaningful effect on their healthy food choices. PMID- 21983205 TI - CSF from amyotrophic lateral sclerosis patients produces glutamate independent death of rat motor brain cortical neurons: protection by resveratrol but not riluzole. AB - The neurotoxic effects of cerebrospinal fluid (CSF) from patients suffering amyotrophic lateral sclerosis (ALS), have been reported by various authors. However, variable results have been communicated and the mechanism of such neurotoxicity has been attributed to excess glutamate concentrations in ALS/CSF. We have studied here the properties of 14 CSFs from control patients and 29 CSFs from patients of ALS. We found that while ALS/CSF impairs the viability of rat brain cortical motoneurons maintained in primary cultures, this effect seemed to be exerted through a glutamate-independent mechanism. Resveratrol protected against such neurotoxic effects and antagonized the [Ca(+2)](c) elevation produced by ALS/CSF. However, riluzole did not afford protection and antagonized the resveratrol-elicited neuroprotective effects. We conclude that ALS/CSF elicited neurotoxicity on in vitro cultures of rat brain cortical motor neurons may become a sound microassay to test available novel multitargeted neuroprotective compounds with potential therapeutic application in ALS patients. PMID- 21983206 TI - Altered glial gene expression, density, and architecture in the visual cortex upon retinal degeneration. AB - Genes encoding the proteins of cytoskeletal intermediate filaments (IF) are tightly regulated, and they are important for establishing neural connections. However, it remains uncertain to what extent neurological disease alters IF gene expression or impacts cells that express IFs. In this study, we determined the onset of visual deficits in a mouse model of progressive retinal degeneration (Pde6b(-) mice; Pde6b(+) mice have normal vision) by observing murine responses to a visual task throughout development, from postnatal day (PND) 21 to adult (N=174 reliable observations). Using Q-PCR, we evaluated whether expression of the genes encoding two Type III IF proteins, glial fibrillary acidic protein (GFAP) and vimentin was altered in the visual cortex before, during, and after the onset of visual deficits. Using immunohistochemical techniques, we investigated the impact of vision loss on the density and morphology of astrocytes that expressed GFAP and vimentin in the visual cortex. We found that Pde6b(-) mice displayed 1) evidence of blindness at PND 49, with visual deficits detected at PND 35, 2) reduced GFAP mRNA expression in the visual cortex between PND 28 and PND 49, and 3) an increased ratio of vimentin:GFAP-labeled astrocytes at PND 49 with reduced GFAP cell body area. Together, these findings demonstrate that retinal degeneration modifies cellular and molecular indices of glial plasticity in a visual system with drastically reduced visual input. The functional consequences of these structural changes remain uncertain. PMID- 21983207 TI - Suppression of acute morphine withdrawal syndrome by adenovirus-mediated beta endorphin in rats. AB - BACKGROUND: Endogenous beta-endorphin (beta-EP) in the central nervous system (CNS) is decreased upon opioid addiction. The current study examined whether exogenous beta-EP, delivered using an adenoviral vector into the CNS could attenuate morphine withdrawal syndrome in rats. METHODS: The model of opioid dependent rats was set up by receiving subcutaneous injection of morphine using an escalating regimen for 6days (5, 10, 20, 40, 50, 60mg/kg, three times/day). The adenovirus mediated beta-EP gene was constructed based on our previous work. The ilea of opioid-dependent rats were isolated and treated with the supernatant of Ad-NEP. The basic and naloxone-induced (4MUm/l) contractions of dependent ilea were recorded. The Ad-NEP was injected into the left lateral ventricle of the addition rats. The expression of the beta-EP gene was verified by radioimmunoassay of the cerebrospinal fluid (CSF) and immunocytochemistry for beta-EP. Withdrawal syndrome was evaluated after intraperitoneal injection of naloxone. RESULTS: The contractions of dependent ilea were attenuated with supernatant containing beta-EP expressed by Ad-NEP. Injection of the Ad-NEP resulted in significant increases in beta-EP level in the CSF and beta-EP positive neurons. Rats receiving adenovirus carrying the beta-EP gene had significantly less severe withdrawal symptoms upon naloxone challenge. CONCLUSIONS: Exogenous beta-EP mediated by adenovirus could attenuate withdrawal syndrome in morphine-dependent rats. PMID- 21983208 TI - Activation of signal transducers and activators of transcription 3 in the hippocampal CA1 region in a rat model of global cerebral ischemic preconditioning. AB - The signal transducers and activators of transcription 3 (STAT3) has been suggested to have neuroprotective roles. However, its role in ischemic preconditioning (PC) is still obscure. In this study, we examined the phosphorylation status of ser727-STAT3, which is necessary for activation of STAT3, and its roles in a rat global ischemia model with or without PC. PC was induced by 3 min of nonlethal ischemia 48 h before 5 min of lethal ischemia. Western blot analysis showed that phospho-ser727-STAT3 significantly increased from 8 to 48 h after nonlethal ischemia, while it increased only for 1h after lethal ischemia and returned to the baseline within 24h. In the preconditioned brains, phospho-ser727-STAT3 was induced at 1 to 4h after lethal ischemia, and decrease of its levels delayed compared to the nonconditioned brains. Immunohistochemistry revealed that phospho-ser727-STAT3 was expressed mainly in CA1 neurons after nonlethal ischemia. Additionally, STAT3 inhibitor peptide treatment prevented PC induced-neuroprotection. These results indicate that phosphorylation of ser727-STAT3 plays an important role in PC induced- neuroptotection. PMID- 21983209 TI - Toxicogenomic investigation on rat testicular toxicity elicited by 1,3 dinitrobenzene. AB - Rats were treated with a single oral dose of 10, 25 and 50mg/kg of 1,3 dinitrobenzene (DNB), and the testis was subjected to a GeneChip microarray analysis. A total of 186 and 304 gene probe sets were up- and down-regulated, respectively, by the DNB treatment, where spermatocyte death and Sertoli cell vacuolation in testis and increased debris of spermatogenic cell in epididymis were noted. The expression profile for four sets of genes were investigated, whose expressions are reported to localize in specific cell types in the seminiferous epithelium, namely Sertoli cells, spermatogonia plus early spermtocytes, pachytene spermatocytes and round spermatids. The data demonstrated that pachytene spermatocyte-specific genes elicited explicit down-regulation in parallel with the progression of spermatocyte death, while other gene sets did not show characteristic expression changes. In addition, Gene Ontology analysis indicated that genes associated with cell adhesion-related genes were significantly enriched in the up-regulated genes following DNB treatment. Cell adhesion-related genes, namely Cdh2, Ctnna1, Vcl, Zyx, Itgb1, Testin, Lamc3, Pvrl2 and Gsn, showed an increase in microarray and the up-regulation of Cdh2 and Testin were confirmed by real time RT-PCR. The gene expression changes of pachytene spermatocyte-specific genes and cell adhesion-related genes were thought to reflect a decrease in the number of spermatocytes and dysfunction of Sertoli-germ cells adhesion junction, and therefore these genes would be potential genomic biomarkers for assessing DNB-type testicular toxicity. PMID- 21983210 TI - The N-glycans of Trichomonas vaginalis contain variable core and antennal modifications. AB - Trichomonad species are widespread unicellular flagellated parasites of vertebrates which interact with their hosts through carbohydrate-lectin interactions. In the past, some data have been accumulated regarding their lipo(phospho)glycans, a major glycoconjugate on their cell surfaces; on the other hand, other than biosynthetic aspects, few details about their N-linked oligosaccharides are known. In this study, we present both mass spectrometric and high-performance liquid chromatography data about the N-glycans of different strains of Trichomonas vaginalis, a parasite of the human reproductive tract. The major structure in all strains examined is a truncated oligomannose form (Man(5)GlcNAc(2)) with alpha1,2-mannose residues, compatible with a previous bioinformatic examination of the glycogenomic potential of T. vaginalis. In addition, dependent on the strain, N-glycans modified by pentose residues, phosphate or phosphoethanolamine and terminal N-acetyllactosamine (Galbeta1,4GlcNAc) units were found. The modification of N-glycans by N acetyllactosamine in at least some strains is shared with the lipo(phospho)glycan and may represent a further interaction partner for host galectins, thereby playing a role in binding of the parasite to host epithelia. On the other hand, the variation in glycosylation between strains may be the result of genetic diversity within this species. PMID- 21983211 TI - The WaaL O-antigen lipopolysaccharide ligase has features in common with metal ion-independent inverting glycosyltransferases. AB - WaaL is a membrane enzyme that catalyzes a key step in lipopolysaccharide (LPS) synthesis: the glycosidic bonding of a sugar at the proximal end of the undecaprenyl-diphosphate (Und-PP) O-antigen with a terminal sugar of the lipid A core oligosaccharide (OS). Utilizing an in vitro assay, we demonstrate here that ligation with purified Escherichia coli WaaL occurs without adenosine-5' triphosphate (ATP) and magnesium ions. Furthermore, E. coli and Pseudomonas aeruginosa WaaL proteins cannot catalyze ATP hydrolysis in vitro. We also show that a lysine substitution of the arginine (Arg)-215 residue renders an active protein, whereas WaaL mutants with alanine replacements in the periplasmic exposed residues Arg-215, Arg-288 and histidine (His)-338 and also the membrane embedded aspartic acid-389 are nonfunctional. An in silico approach, combining predicted topological information with the analysis of sequence conservation, confirms the importance of a positive charge at the small periplasmic loop of WaaL, since an Arg corresponding to Arg-215 was found at a similar position in all the WaaL homologs. Also, a universally conserved H[NSQ]X(9)GXX[GTY] motif spanning the C-terminal end of the predicted large periplasmic loop and the membrane boundary of the transmembrane helix was identified. The His residue in this motif corresponds to His-338. A survey of LPS structures in which the linkage between O-antigen and lipid A-core OS was elucidated reveals that it is always in the beta-configuration, whereas the sugars bound to Und-PP are in the alpha-configuration. Together, our biochemical and in silico data argue that WaaL proteins use a common reaction mechanism and share features of metal ion independent inverting glycosyltransferases. PMID- 21983212 TI - Pathogens implicated in acute otitis media failures after 7-valent pneumococcal conjugate vaccine implementation in France: distribution, serotypes, and resistance levels. AB - BACKGROUND: Before 7-valent pneumococcal conjugate vaccine (PCV7) implementation in France, several studies had described the microbiology of acute otitis media (AOM) treatment failures. The causative pathogens were Streptococcus pneumoniae (Sp) followed by nontypable Haemophilus influenzae (NTHi). The aim of this study was to describe the epidemiology of pathogens involved in AOM treatment failures or recurrences. METHODS: This French multicentric prospective study enrolled 143 children with AOM treatment failure between 2007 and 2009 observed by 8 ear, nose, and throat specialists. Failure was defined as the persistence of AOM symptoms after at least 48 hours of antibiotic therapy or their recurrence within 4 days after the end of treatment. Standardized history and physical examination findings were recorded, and culture of middle ear fluid (MEF) was obtained. RESULTS: Mean age was 16.9 +/- 9.9 months (median, 13.7). Eighty-eight percent of children had received more than 1 dose of PCV7, and 70.6% attended day care. The most common antibiotic used at the time of treatment failure or recurrence was a combination of amoxicillin and clavulanate (51.1%). Bacteriologic sampling demonstrated that in 35% of cases (n=50), no otopathogen was cultured at the time of treatment failure or recurrence. Similar proportions of Sp and NTHi were observed in the 86 patients (60.1%) from whom only a single species was recovered from MEF (46.5% for Sp, n=40 and 45.3% for NTHi, n=39). Among Sp strains, 4.4% were penicillin susceptible, 77.8% were penicillin intermediate, and 17.8% were fully penicillin resistant, and serotype 19A represented 84.5% of all serotypes detected. Among NTHi isolates, 15.5% (n=7) were beta-lactamase-producing strains (including 2 strains with only this mechanism of resistance), and strains with reduced susceptibility by changes in protein binding to penicillin (beta lactamase-negative ampicillin resistant strains) represented 35.5% of cases. Among the 50 sterile MEF samples, polymerase chain reaction was performed in 32, of which 4 were positive for HI, 3 for Sp, and 3 for both. CONCLUSIONS: Among children with AOM treatment failures in France, Sp and NTHi were equally distributed; 19A was the main Sp serotype, and the main resistance mechanism for NTHi was beta-lactamase-negative ampicillin resistance. PMID- 21983213 TI - Prevalence of congenital anomalies in infants with in utero exposure to antiretrovirals. AB - BACKGROUND: Although use of efficacious interventions, including antiretrovirals (ARVs), has dramatically reduced the rate of mother-to-child transmission of human immunodeficiency virus, the safety of in utero ARV exposure remains of concern. METHODS: Data regarding 1112 infants enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Group protocol P1025 born between 2002 and 2007 were analyzed for this study. Congenital anomalies were classified based on the Metropolitan Atlanta Congenital Defects Program guidelines. Associations between congenital anomalies and timing of first in utero exposure to ARVs were evaluated by logistic regression analysis. RESULTS: Congenital anomalies were identified and confirmed in 61 of the 1112 infants, resulting in a prevalence of 5.49/100 live births (95% confidence interval, 4.22 6.99). Among the 80 anomalies identified, the organ systems involved included cardiovascular (n = 33), musculoskeletal (n = 15), renal (n = 9), genitourinary (n = 6), craniofacial (n = 4), and central nervous system (n = 2). First trimester exposure to efavirenz was associated with a significantly increased risk of congenital anomalies (odds ratio, 2.84; 95% confidence interval, 1.13 7.16). No significant associations were observed between exposure to other individual ARVs or classes of ARVs started at any time during pregnancy and infant congenital anomalies. CONCLUSIONS: The observed rate of congenital anomalies in this cohort is higher than previously reported for the general population, but it is consistent with rates observed in other recent studies of children born to human immunodeficiency virus-infected women. Cardiovascular anomalies occurred most frequently. With the exception of a known teratogen (efavirenz), no statistically significant associations between in utero exposure to ARVs and congenital anomalies were identified. PMID- 21983214 TI - Hemagglutination inhibition antibody titers as a correlate of protection for inactivated influenza vaccines in children. AB - INTRODUCTION: The hemagglutination inhibition (HI) titer of 1:40, which has been recognized as an immunologic correlate corresponding to a 50% reduction in the risk of contracting influenza, is based on studies in adults. Neither seasonal nor challenge-based correlates have been evaluated in children. METHODS: A total of 4707 influenza vaccine-naive healthy children 6 to 72 months old were randomized in a ratio of 2:2:1 to receive 2 doses of MF-59-adjuvanted influenza vaccine (Novartis Vaccines), trivalent inactivated influenza vaccine subunit (trivalent inactivated influenza vaccine control, GSK), or a saline placebo during the 2007 to 2008 and 2008 to 2009 influenza seasons. The second dose was given 30 days after dose 1. Clinical influenza-like illnesses cases identified by active surveillance were confirmed by reverse transcription polymerase chain reaction testing for influenza. Vaccine immunogenicity 50 days after dose 1 was evaluated in a subset of 777 children. RESULTS: Immunogenicity and efficacy results for H3N2 were evaluated against the Prentice criteria, which confirmed that the immunogenicity results warranted estimation of an immunologic correlate. We then used the Dunning model fitting the H3N2 antibody titers at day 50 and the influenza cases observed in the immunogenicity subset to estimate a correlate of protection. This analysis revealed that a cutoff HI titer of 1:110 was associated with the conventional 50% clinical protection rate against infection during the entire season, and titers of 1:215, 1:330, and 1:629 predicated protection rates of 70%, 80%, and 90%, respectively. The conventional adult HI titer of 1:40 was only associated with 22% protection. CONCLUSIONS: The use of the 1:40 HI adult correlate of protection is not appropriate when evaluating influenza vaccines in children. Although a cutoff of 1:110 may be used to predict the conventional 50% clinical protection rate, a titer of 1:330 would predict an 80% protective level, which would seem to be more desirable from a public health perspective. PMID- 21983215 TI - A strong tuberculin reaction in primary school children predicts tuberculosis in adolescence. AB - BACKGROUND: In Hong Kong, neonatal bacillus Calmette-Guerin vaccination coverage has been around 99% since 1970. Children younger than 14 years of age appear to have a relatively low risk of tuberculosis (TB), but the risk of TB increases rapidly after 15 years of age to a secondary peak in young adulthood. METHODS: We followed prospectively 19,383 students who were 6 to 10 years of age participating in the 1999/2000 bacillus Calmette-Guerin revaccination program by cross-matching with the territory-wide TB registry until December 31, 2010, using the identity card number as a unique identifier. RESULTS: After 214,753 person years of follow-up, 44 active TB cases (22 culture-confirmed) were detected for an overall incidence of 20.5/100,000 person-years. The incidence differed significantly by baseline tuberculin reaction sizes (13.0, 18.8, 22.5, 280.4 per 100,000 person-years for reaction size of 0-4, 5-9, 10-14, and >=15 mm, respectively, P < 0.001). Consistent results were observed for culture-confirmed cases and after adjustment for gender and baseline age. For those with tuberculin reaction size >=15 mm, the incidence of TB was significantly higher beyond the age of 15 years than for those less than 15 years (608.1 vs. 37.5 per 100,000 person-years, P < 0.001). Although older baseline age was associated with larger tuberculin reaction sizes, it did not independently predict subsequent development of disease. CONCLUSION: Strong tuberculin reactions in primary school children predicted TB in adolescents after an initial quiescent period. Endogenous reactivation, possibly related to changes in host immunity, might account for the upsurge of TB in adolescence. PMID- 21983216 TI - Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine in children previously immunized with 7-valent pneumococcal conjugate vaccine. AB - BACKGROUND: The 7-valent pneumococcal conjugate vaccine (PCV7) has proven highly effective in preventing diseases caused by Streptococcus pneumoniae; however, in some regions, serotype coverage is limited. A recently licensed 13-valent PCV (PCV13) was developed to provide additional coverage globally. Children previously vaccinated with PCV7 could benefit from supplemental vaccination with PCV13 to provide protection against the 6 additional serotypes in PCV13. This open-label study evaluated the immunogenicity and safety of administering PCV13 to healthy children previously vaccinated with PCV7. METHODS: Children between 15 months and 2 years of age (group 1) received 2 doses of PCV13; children between 2 and 5 years (group 2) received 1 dose. Antibodies (immunoglobulin G) against the polysaccharide antigens in PCV13 were measured before vaccination and 1 month after the final dose. Solicited local and systemic adverse events (AEs) were collected for 7 days postvaccination. Unsolicited and serious AEs were collected throughout. RESULTS: A total of 284 subjects (group 1: n = 109; group 2: n = 175) had blood available for testing. Antipneumococcal immunoglobulin G geometric mean fold rises ranged from 2- to 19-fold for the PCV7 serotypes and from approximately 2- to 124-fold for the 6 additional serotypes. Additionally, postvaccination titers in excess of 0.35 MUg/mL, the serologic correlate of immunity against pneumococcus for children, occurred in >=98% of subjects in both groups for 12 of the 13 serotypes in PCV13. Slightly lower percentage of subjects, 94.5% and 92% of subjects in group 1 and group 2, respectively, had postvaccine titers for serotype 3 exceeding the serologic correlate of immunity. Reactogenicity was typically mild and self-limited, and unsolicited AEs reported were generally consistent with common childhood illnesses. CONCLUSION: PCV13 was safe and immunogenic when administered to children who had previously received PCV7, and can be used for supplemental vaccination to provide additional protection against the 6 additional serotypes. PMID- 21983217 TI - Widespread systemic embolization with isolated tricuspid valve endocarditis. AB - Concurrent systemic and pulmonary septic emboli from isolated right-sided infective endocarditis are rare. One mechanism described is that of intrapulmonary shunting. We describe a case of widespread pulmonary and systemic septic embolization with sequelae in an intravenous drug user with concomitant chronic hepatitis C infection and discuss possible mechanisms involved in the pathogenesis. PMID- 21983218 TI - Changes in optic nerve head blood flow, visual function, and retinal histology in hypercholesterolemic rabbits. AB - We investigated the effects of hypercholesterolemia on optic nerve head (ONH) blood flow, visual function, and retinal histology in a rabbit model. Hypercholesterolemia was induced in rabbits by feeding them a high cholesterol (1%) diet for 12 weeks. Changes in blood pressure, intraocular pressure (IOP), and ONH blood flow were monitored at 6 and 12 weeks after treatment. The autoregulation of ONH blood flow as detected by laser speckle flowgraphy was verified by an artificial elevation of IOP at 12 weeks. Visually evoked potentials (VEPs) were also recorded and analyzed at 6 and 12 weeks. Finally, a histological examination as well as immunohistochemistry to endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) was performed. In the hypercholesterolemic rabbits, blood pressure, IOP, and ONH blood flow did not alter significantly throughout this study. The autoregulation of ONH blood flow against IOP elevation was found to be impaired at 12 weeks. The amplitudes of the first negative peak of VEPs were diminished. Both the density of the retinal ganglion cells and the thickness of the inner nuclear layer and photoreceptor cell layer were reduced. Immunoreactivity to eNOS was reduced and that to iNOS was enhanced in the hypercholesterolemic rabbits compared to those in the normal control rabbits. The results of this study show that hypercholesterolemia induces impairment in the autoregulation of ONH blood flow and deterioration in visual function and histology. Downregulation of eNOS activity might be one of the causes for impairment of the autoregulation. Enhanced activity of iNOS might be involved in the impaired visual function and histology. PMID- 21983219 TI - The solid-liquid interface free-energy of Pb: comparison of theory and experiments. AB - The solid-liquid interface free-energy gamma(sl) is a key parameter controlling nucleation and growth during solidification and other phenomena. Different experimental techniques are available for its evaluation but results are often widely scattered and strongly depend on the technique used. One of the best examples in this sense is the case of elemental Pb, with values for gamma(sl) differing by as much as 150% between nucleation rate experiments and contact angle data. Even using simple many-body potentials, theoretical calculations of gamma(sl) can exceed this level of accuracy and thus be employed to assess the present experimental data. To this purpose, atomistic calculations are performed in conjunction with two different many-body potentials for Pb. These show good agreement with nucleation rate and depression of melting point experiments and support the case for a reassessment of the measurements reported from contact angle data. Possible sources of errors that might have affected these experiments are critically discussed, showing how the magnitude of the anisotropy in the interfacial free energies can be important in closing the gap between the different sets of experimental data. PMID- 21983220 TI - Urinary thromboxane B2 and thromboxane receptors in bladder cancer: opportunity for detection and monitoring. AB - We have previously found increased expression of thromboxane synthase (TXAS) and thromboxane receptor (TP) beta isoform in the tissues of patients with bladder cancer. Studies in cell lines and mice have indicated a potential significant role of the thromboxane signaling pathway in the pathogenesis of human bladder cancer. This study was designed to determine if the changes observed in the tissues of patients with bladder cancer were mirrored by changes in the urine of these patients. We found increased levels of thromboxane B(2) (TXB(2)) the major metabolite of TXAS and increased levels of the TPbeta receptor. These results raised the possibility that patients with bladder cancer may be followed for progression or remission of their disease by quantitation of these substances in their urine. PMID- 21983221 TI - Role of the distal convoluted tubule in renal Mg2+ handling: molecular lessons from inherited hypomagnesemia. AB - In healthy individuals, Mg(2+) homeostasis is tightly regulated by the concerted action of intestinal absorption, exchange with bone, and renal excretion. The kidney, more precisely the distal convoluted tubule (DCT), is the final determinant of plasma Mg(2+) concentrations. Positional cloning strategies in families with hereditary hypomagnesemia identified defects in several proteins localized in the DCT as causative factors. So far, the identified actors involved in Mg(2+) handling in the DCT include: the transient receptor potential channel melastatin member 6, the pro-epidermal growth factor, the thiazide-sensitive Na(+)-Cl(-) cotransporter, the gamma-subunit of the Na(+)/K(+)-ATPase, the hepatocyte nuclear factor 1B, the potassium channels Kv1.1 and Kir4.1, and the cyclin M2. In the years to come, the identification of new magnesiotropic genes and related proteins will further clarify the role of the kidney in Mg(2+) homeostasis, and will potentially lead to new therapeutic approaches for hypomagnesemia. PMID- 21983222 TI - Designing for healthy living: supporting reflectivity on interactions in healthcare. AB - The design of an efficient and effective healthcare services is part of the design for healthy living. Contemporary models of health rely on a deeper involvement of the patient in the decision-making through the steps of the health journey. In these methods, the quality of practitioner-patient interaction is central to the successful processes and patient participation. The quality of these interactions and the ability of both medical practitioners and patients to reflect on each session is part of the design strategies for healthy living. Interactions rely on extensive, effective and empowering communication between practitioner and patient. The purpose of this work is to address the recognition of this importance, evidenced from the broad and diverse communication training for practitioners, by enabling the capture of information about the quality of these interactions. Captured information has to be encoded in a way that enables computer reasoning with it, as well as delivered to patients and practitioners in ways that allow quick interpretation from respective sides. We present the mechanics of the development of a visual language and analysis system enabling visual reasoning about the quality of interactions. The visual knowledge representation is designed based on aspects of human movement. Such design is justified from the fact that human possess implicit knowledge about human movement. The paper presents KIA (Kinetic Inter-Acting) encoding system that is the foundation of the visual language and respective visual analysis method. KIA enables both humans and machines to utilise information about how interactions unfold, which is necessary for practitioner-patient interaction. The paper concludes with discussion of KIA approach and technology in terms of the implications for designing for healthy living. PMID- 21983223 TI - A systematic review of studies concerning observer agreement during medical specialist diagnosis using videoconferencing. AB - We conducted a systematic review of studies of observer agreement for medical specialist diagnosis via videoconferencing. The review was based on searches of electronic databases and a hand search of relevant journals and reference lists between 1966 and June 2010. There were 20 studies comparing videoconferencing diagnosis with a non-telemedicine alternative by reporting a measure of agreement. Half of the studies were in the field of dermatology; these studies provided solid support for the reliability of videoconferencing. The other 10 studies were in psychiatry, geriatrics, minor injuries, neurology and rheumatology. Reliability of diagnosis via videoconferencing was confirmed in all studies. In the studies where physical examination was an element of the diagnostic process, results were reliable but authors recommended greater care during the diagnostic process (e.g. good equipment, onsite support, additional camera angles). Four studies incorporated a second group to measure agreement in paired face-to-face assessments. Although useful evidence for the reliability of diagnosis via videoconferencing was provided by the studies in the review, the range of medical specialties was small. The variation in research methodology and statistical analysis suggests a lack of clarity about which research design is appropriate for measuring observer agreement in relation to diagnostic reliability. PMID- 21983224 TI - Triage and patient satisfaction among callers in Swedish computer-supported telephone advice nursing. AB - We investigated satisfaction with a Swedish telenursing service and the health care-seeking behaviour among callers who received a less urgent level of health care than they expected. A postal questionnaire was sent to a random selection of callers (n = 273) to Swedish Healthcare Direct in October 2008. The 'cases' were 18 callers where the telenurse recommended a lower level of health care than the caller expected and who were not in complete agreement with the nurse. The 'controls' were 22 callers who either received a lower recommendation, or were in disagreement with the recommendation. There were no differences between cases, controls and other callers regarding background factors or the telenurse classification of emergency. However, both cases and controls considered their need for health care as more urgent than the other callers. An independent test of the nurses' reception, ability to listen and to take notice of the callers' health problem, showed that nurses who had served cases, had received a significantly lower rating than other nurses. For nurses who had served controls, there was no such difference in rating. Cases and controls had fewer subsequent care visits than other callers, in the three days following the call, although the proportion of emergency visits was higher among cases and controls compared to other callers. If the caller and the nurse disagree about the nurse's recommendations, the consequence can be a dissatisfied caller and more visits to unnecessary high levels of health care. Further training of the nurses may improve the telenurse service. PMID- 21983225 TI - Sodium arsenite and cadmium chloride induction of proteasomal inhibition and HSP accumulation in Xenopus laevis A6 kidney epithelial cells. AB - Sodium arsenite (NA) and cadmium chloride (CdCl(2)) are relatively abundant environmental toxicants that have multiple toxic effects including carcinogenesis, dysfunction of gene regulation and DNA and protein damage. In the present study, treatment of Xenopus laevis A6 kidney epithelial cells with concentrations of NA (20-30 MUM) or CdCl(2) (100-200 MUM) that induced HSP30 and HSP70 accumulation also produced an increase in the relative levels of ubiquitinated protein. Actin protein levels were unchanged in these experiments. In time course experiments, the levels of ubiquitinated protein and HSPs increased over a 24h exposure to NA or CdCl(2). Furthermore, treatment of cells with NA or CdCl(2) reduced the relative levels of proteasome chymotrypsin (CT) like activity compared to control. Interestingly, pretreatment of cells with the HSP accumulation inhibitor, KNK437, prior to NA or CdCl(2) exposure decreased the relative levels of ubiquitinated protein as well as HSP30 and HSP70. A similar finding was made with ubiquitinated protein induced by proteasomal inhibitors, MG132 and celastrol, known to induce HSP accumulation in A6 cells. However, the NA- or CdCl(2)-induced decrease in proteasome CT-like activity was not altered by KNK437 pretreatment. This study has shown for the first time in poikilothermic vertebrates that NA and CdCl(2) can inhibit proteasomal activity and that there is a possible association between HSP accumulation and the mechanism of protein ubiquitination. PMID- 21983227 TI - Effects of maternal stress coping style on offspring characteristics in rainbow trout (Oncorhynchus mykiss). AB - Maternal size, age, and allostatic load influence offspring size, development, and survival. Some of these effects have been attributed to the release of glucocorticoids, and individual variation in these stress hormones is related to a number of traits. Correlated traits are often clustered and used to define the proactive and reactive stress coping styles. Although stress coping styles have been identified in a number of animal groups, little is known about the coupling between stress coping style and offspring characteristics. In the present study, plasma cortisol levels in ovulated mothers and cortisol levels in non-fertilized eggs from two rainbow trout (Oncorhynchus mykiss) strains selected for high (HR) and low (LR) post-stress plasma cortisol levels were compared. Offspring characteristics such as egg size, larval growth, and energy reserves also were compared between the two strains. Maternal plasma and egg cortisol levels were correlated, but no difference between the HR and LR strains was detected in either parameter. LR females produced larger eggs, and larvae with larger yolk sacs compared to HR females, however no differences in larval body size (excluding the yolk) was detected between strains. Considering that the HR and LR strains have a number of correlated behavioral and physiological traits that resemble the reactive and proactive stress coping styles, respectively, the results suggest that proactive mothers invest more energy into their offspring, producing larvae with larger energy reserves. It is possible that larger energy reserves in proactive larvae support the energy requirement for establishing and defending territory in salmonid fish. Furthermore, in the present study we found a positive relationship between mother plasma cortisol and egg cortisol; however neither mother plasma cortisol nor egg cortisol differed between strains. These results indicate that cortisol endowment from the mother to the offspring plays a minor role in the transfer of the behavioral and physiological traits which separates these strains. PMID- 21983226 TI - Neuroticism, acculturation and the cortisol awakening response in Mexican American adults. AB - Neuroticism is associated with greater susceptibility to the adverse effects of stress and greater exposure to the stressors associated with acculturation in U.S. born Mexican Americans. Neuroticism and acculturation have been associated with injury to crucial stress response systems and are known risk factors for certain mood and anxiety disorders. The purpose of the current study was to examine the effects of neuroticism, and acculturation on the cortisol awakening response (CAR) in healthy Mexican-American adults. Salivary cortisol samples were collected at awakening and 30, 45, and 60 min thereafter, on two consecutive weekdays from 59 healthy Mexican American adult males (26) and females (33), ages 18 to 38 years. Participants were assessed for level of neuroticism and acculturation. Data were analyzed using a mixed effects regression model with repeated measures at four time points. Results showed a significant Neuroticism*Acculturation*Time interaction. The CAR was virtually eliminated in highly acculturated Mexican Americans with greater Anglo orientation and high neuroticism compared with less acculturated Mexican Americans with greater Mexican orientation and lower neuroticism. Findings suggest that some Mexican Americans with high levels of neuroticism may be particularly susceptible to certain challenges and stressors associated with acculturation leading over time to the development of allostatic load, desensitization of the Hypothalamic CRF system and attenuation of the CAR. PMID- 21983228 TI - Functionally similar acoustic signals in the corncrake (Crex crex) transmit information about different states of the sender during aggressive interactions. AB - We combined playback experiments with hormonal manipulations to study the information content of acoustic signals during aggressive interactions between male corncrakes. During territorial conflicts, fights are uncommon, but the intensity of signaling usually increases. Such signals can be temporally and contextually associated with many aggressive behaviors and most likely function as threats or as indicators of the sender's quality or motivation. However, such correlational data are unsatisfactory for the proper interpretation of the function and information content of signals. Experimental tests are required to determine whether signals and aggressive behaviors are controlled by common or independent mechanisms. In our experiment, we assigned subjects to four groups: testosterone-implanted birds, flutamide-implanted birds, birds with empty implants, and non-captured control birds. Males produced two types of calls (quiet soft calls and loud broadcast calls), both of which are known to be reliable predictors of aggressive escalation. When testosterone action was blocked with flutamide, males significantly limited the amount of time spent close to the playback speaker and stopped responding to playback with soft calls. Broadcast calling was unaffected by the blockage of testosterone. Conversely, increased levels of testosterone neither affected calling nor the time spent near the speaker, indicating a permissive, rather than a graded effect of androgens. We concluded that, despite the seemingly similar function, both signals may transmit information about different states of the sender; soft calls seem to imply a threat of force, while broadcast calls appear to be more similar to an announcement, which is only indirectly associated with a male's aggressive behavior. PMID- 21983230 TI - Inhibiting influence of testosterone on stress responsiveness during adolescence. AB - The maturation of the hypothalamo-pituitary-adrenal (HPA) axis is a key-component of the changes that occur during adolescence. In guinea pigs, HPA responsiveness during late adolescence depends strongly on the quantity and quality of social interactions: Males that lived in a large mixed-sex colony over the course of adolescence exhibit a lower stress response than males that were kept in pairs (one male/one female). Since colony-housed males have higher testosterone (T) levels than pair-housed males, and inhibiting effects of T on HPA function are well known, we tested the hypothesis that the decrease in stress responsiveness found in colony-housed males is due to their high T concentrations. We manipulated T levels in two experiments: 1) gonadectomy/sham-gonadectomy of colony-housed males (which usually have high T levels), 2) application of T undecanoate/vehicle to pair-housed males (which usually have low T levels). As expected, gonadectomized males showed a significantly increased stress response in comparison with sham-gonadectomized males, and T-injected males had a significantly lower stress response than vehicle-injected males. Both experiments thus confirm an inhibiting effect of T on HPA responsiveness during adolescence, which can mediate the influence of social interactions. The reduction in stress responsiveness is hypothesized to have a biologically adaptive value: A sudden increase in glucocorticoid concentrations can enhance aggressive behavior. Thus, pair-housed males might be adapted to aggressively defend their female ('resource defense strategy'), whereas colony-housed males display little aggressive behavior and are capable of integrating themselves into a colony ('queuing strategy'). PMID- 21983229 TI - Testosterone and sport: current perspectives. AB - Testosterone and other anabolic-androgenic steroids enhance athletic performance in men and women. As a result, exogenous androgen is banned from most competitive sports. However, due to variability in endogenous secretion, and similarities with exogenous testosterone, it has been challenging to establish allowable limits for testosterone in competition. Endogenous androgen production is dynamically regulated by both exercise and winning in competition. Furthermore, testosterone may promote athletic performance, not only through its long-term anabolic actions, but also through rapid effects on behavior. In women, excess production of endogenous testosterone due to inborn disorders of sexual development (DSD) may convey a competitive advantage. For many years, female competitors have been subject to tests of sexual genotype and phenotype known as gender verification. Although gender verification has not identified any normal man competing as a woman, this process has identified women athletes with DSD. As understanding of DSD has expanded in recent years, women with DSD are increasingly able to continue athletic competition. PMID- 21983231 TI - Visualization of cortical lamination patterns with magnetic resonance imaging. AB - The ability to image the cortex laminar arrangements in vivo is one of the holy grails of neuroscience. Recent studies have visualized the cortical layers ex vivo and in vivo (on a small region of interest) using high-resolution T(1)/T(2) magnetic resonance imaging (MRI). In this study, we used inversion-recovery (IR) MRI to increase the sensitivity of MRI toward cortical architecture and achieving whole-brain characterization of the layers, in vivo, in 3D on humans and rats. Using the IR measurements, we computed 3D signal intensity plots along the cortex termed corticograms to characterize cortical substructures. We found that cluster analyses of the multi-IR images along the cortex divides it into at least 6 laminar compartments. To validate our observations, we compared the IR-MRI analysis with histology and revealed a correspondence, although these 2 measures do not represent similar quantities. The abilities of the method to segment the cortex into layers were demonstrated on the striate cortex (visualizing the stripe of Gennari) and on the frontal cortex. We conclude that the presented methodology can serve as means to study and characterize individual cortical architecture and organization. PMID- 21983232 TI - Future direct and indirect costs of obesity and the influence of gaining weight: results from the MONICA/KORA cohort studies, 1995-2005. AB - Over the last two decades, the prevalence of obesity has risen worldwide. As obesity is a confirmed risk factor for a number of diseases, its increasing prevalence nurtures the supposition that obesity may present a growing and significant economic burden to society. The objective of this study is to analyse the correlation between body mass index (BMI) and future direct and indirect costs, as well as the correlation between changing BMI and future in(direct) costs. Health care utilisation and productivity losses were based on data from 2581 participants aged 25-65 years (1994/95) from two cross-sectional, population representative health surveys (MONICA/KORA-survey-S3 1994/95 and follow-up KORA survey-F3 2004/05) in Augsburg, Germany. The predicted average adjusted total direct costs per year and per user were estimated to be ?1029-(healthy weight), ?1093-(overweight) and ?1040-(obesity). There are significantly greater future costs in the utilisation of general practitioners per user and per year at higher obesity levels (?72; ?75; ?96). The average total direct costs per person for those who stay in the same BMI class are ?982, ?1000 and ?973. An overweight participant who becomes obese incurs significant costs of internists of ?160 compared with those who remain overweight (?124). An overweight user incurs indirect costs of ?2474, compared with ?2136 for those who remain a healthy weight. There is a trend for higher predicted (in)direct costs when people are overweight or obese compared with healthy weight persons 10 years earlier. Potential cost savings could be attained if preventive programs effectively targeted these individuals. PMID- 21983233 TI - Biopolymers production from mixed cultures and pyrolysis by-products. AB - Polyhydroxyalkanoates (PHAs) production from low value substrates and/or byproducts represents an economical and environmental promising alternative to established industrial manufacture methods. Bio-oil resulting from the fast pyrolysis of chicken beds was used as substrate to select a mixed microbial culture (MMC) able to produce PHA under feast/famine conditions. In this study a maximum PHA content of 9.2% (g/g cell dry weight) was achieved in a sequencing batch reactor (SBR) operated for culture selection. The PHA obtained with bio-oil as a carbon source was a copolymer composed by 70% of hydroxybutyrate (HB) and 30% of hydroxyvalerate (HV) monomers. Similar results have been reported by other studies that use real complex substrates for culture selection indicating that bio-oil can be a promising feedstock to produce PHAs using MMC. To the best of our knowledge this is the first study that demonstrated the use of bio-oil resulting from fast pyrolysis as a possibly feedstock to produce short chain length polyhydroxyalkanoates. PMID- 21983234 TI - Extracellular serine proteases from Stenotrophomonas maltophilia: Screening, isolation and heterologous expression in E. coli. AB - A large strain collection comprising antagonistic bacteria was screened for novel detergent proteases. Several strains displayed protease activity on agar plates containing skim milk but were inactive in liquid media. Encapsulation of cells in alginate beads induced protease production. Stenotrophomonas maltophilia emerged as best performer under washing conditions. For identification of wash-active proteases, four extracellular serine proteases called StmPr1, StmPr2, StmPr3 and StmPr4 were cloned. StmPr2 and StmPr4 were sufficiently overexpressed in E. coli. Expression of StmPr1 and StmPr3 resulted in unprocessed, insoluble protein. Truncation of most of the C-terminal domain which has been identified by enzyme modeling succeeded in expression of soluble, active StmPr1 but failed in case of StmPr3. From laundry application tests StmPr2 turned out to be a highly wash active protease at 45 degrees C. Specific activity of StmPr2 determined with suc L-Ala-L-Ala-L-Pro-l-Phe-p-nitroanilide as the substrate was 17+/-2U/mg. In addition we determined the kinetic parameters and cleavage preferences of protease StmPr2. PMID- 21983235 TI - Immobilization of Delftia tsuruhatensis in macro-porous cellulose and biodegradation of phenolic compounds in repeated batch process. AB - Delftia tsuruhatensis BM90, previously isolated from Tyrrhenian Sea and selected for its ability to degrade a wide array of phenolic compounds, was immobilized in chemically modified macro porous cellulose. The development of bacterial adhesion on the selected carrier was monitored by scanning electron microscopy. Evident colonization started already after 8h of incubation. After 72h, almost all the carrier surface was covered by the bacterial cells. Extracellular bacterial structures, such as pili or fimbriae, contributed to carrier colonization and cell attachment. Immobilized cells of D. tsuruhatensis were tested for their ability to biodegrade a pool of 20 phenols in repeated batch process. During the first activation batch (72h), 90% of phenols degradation was obtained already in 48h. In the subsequent batches (up to 360h), same degradation was obtained after 24h only. By contrast, free cells were slower: to obtain almost same degradation, 48h were needed. Thus, process productivity, achieved by the immobilized cells, was double than that of free cells. Specific activity was also higher suggesting that the use of immobilized D. tsuruhatensis BM90 could be considered very promising in order to obtain an efficient reusable biocatalyst for long-term treatment of phenols containing effluents. PMID- 21983236 TI - Testosterone-mediated sex differences in the face shape during adolescence: subjective impressions and objective features. AB - Sex identification of a face is essential for social cognition. Still, perceptual cues indicating the sex of a face, and mechanisms underlying their development, remain poorly understood. Previously, our group described objective age- and sex related differences in faces of healthy male and female adolescents (12-18 years of age), as derived from magnetic resonance images (MRIs) of the adolescents' heads. In this study, we presented these adolescent faces to 60 female raters to determine which facial features most reliably predicted subjective sex identification. Identification accuracy correlated highly with specific MRI derived facial features (e.g. broader forehead, chin, jaw, and nose). Facial features that most reliably cued male identity were associated with plasma levels of testosterone (above and beyond age). Perceptible sex differences in face shape are thus associated with specific facial features whose emergence may be, in part, driven by testosterone. PMID- 21983237 TI - Maternal tendencies in women are associated with estrogen levels and facial femininity. AB - Previous studies have shown that women with higher maternal tendencies are shorter and have lower testosterone levels than those with lower maternal tendencies. Here we report two studies that investigated the relationships between maternal tendencies and two further measures of physical masculinization/feminization; urinary estrogen metabolite (estrone-3-glucuronide: E1-3G) levels (Study 1) and rated facial femininity (Study 2). In Study 1, nulliparous women reported both their ideal number of children and ideal own age at first child and also provided urine samples. There was a significant positive correlation between measured late-follicular estrogen levels and reported ideal number of children. In Study 2, analyses of facial cues in two independent samples of women showed that the average facial characteristics of women who reported desiring many children were rated as more feminine than those desiring fewer children. Collectively, these results support the proposal that maternal tendencies are related to physical feminization and that this effect may, at least in part, reflect the influence of the hormone estrogen. PMID- 21983239 TI - How to reduce the incidence of neuropathic pain: sentinel node biopsy for diagnosis of metastatic malignant melanoma. PMID- 21983238 TI - Changes in salivary testosterone concentrations and subsequent voluntary squat performance following the presentation of short video clips. AB - Previous studies have shown that visual images can produce rapid changes in testosterone concentrations. We explored the acute effects of video clips on salivary testosterone and cortisol concentrations and subsequent voluntary squat performance in highly trained male athletes (n=12). Saliva samples were collected on 6 occasions immediately before and 15 min after watching a brief video clip (approximately 4 min in duration) on a computer screen. The watching of a sad, erotic, aggressive, training motivational, humorous or a neutral control clip was randomised. Subjects then performed a squat workout aimed at producing a 3 repetition maximum (3RM) lift. Significant (P<0.001) relative (%) increases in testosterone concentrations were noted with watching the erotic, humorous, aggressive and training videos (versus control and sad), with testosterone decreasing significantly (versus control) after the sad clip. The aggressive video also produced an elevated cortisol response (% change) and more so than the control and humorous videos (P<0.001). A significant (P<0.003) improvement in 3RM performance was noted after the erotic, aggressive and training clips (versus control). A strong within-individual correlation (mean r=0.85) was also noted between the relative changes in testosterone and the 3RM squats across all video sessions (P<0.001). In conclusion, different video clips were associated with different changes in salivary free hormone concentrations and the relative changes in testosterone closely mapped 3RM squat performance in a group of highly trained males. Thus, speculatively, using short video presentations in the pre workout environment offers an opportunity for understanding the outcomes of hormonal change, athlete behaviour and subsequent voluntary performance. PMID- 21983240 TI - New insights into the organisation and intracellular localisation of the two subunits of glucose-6-phosphatase. AB - Glucose-6 phosphatase (G6Pase), a key enzyme of glucose homeostasis, catalyses the hydrolysis of glucose-6 phosphate (G6P) to glucose and inorganic phosphate. A deficiency in G6Pase activity causes type 1 glycogen storage disease (GSD-1), mainly characterised by hypoglycaemia. Genetic analyses of the two forms of this rare disease have shown that the G6Pase system consists of two proteins, a catalytic subunit (G6PC) responsible for GSD-1a, and a G6P translocase (G6PT), responsible for GSD-1b. However, since their identification, few investigations concerning their structural relationship have been made. In this study, we investigated the localisation and membrane organisation of the G6Pase complex. To this aim, we developed chimera proteins by adding a fluorescent protein to the C terminal ends of both subunits. The G6PC and G6PT fluorescent chimeras were both addressed to perinuclear membranes as previously suggested, but also to vesicles throughout the cytoplasm. We demonstrated that both proteins strongly colocalised in perinuclear membranes. Then, we studied G6PT organisation in the membrane. We highlighted FRET between the labelled C and N termini of G6PT. The intramolecular FRET of this G6PT chimera was 27%. The coexpression of unlabelled G6PC did not modify this FRET intensity. Finally, the chimera constructs generated in this work enabled us for the first time to analyze the relationship between GSD-1 mutations and the intracellular localisation of both G6Pase subunits. We showed that GSD1 mutations did neither alter the G6PC or G6PT chimera localisation, nor the interaction between G6PT termini. In conclusion, our results provide novel information on the intracellular distribution and organisation of the G6Pase complex. PMID- 21983241 TI - Fluorodeoxyglucose positron emission tomography: emerging roles in the evaluation of putative Alzheimer's disease-modifying treatments. AB - Alzheimer's disease (AD) is associated with characteristic and progressive reductions in flourodeoxyglucose positron emission tomography (FDG PET) measurements of the regional cerebral metabolic rate for glucose. These reductions begin years before the onset of symptoms, are correlated with clinical severity, and may help predict an affected patient's clinical course and neuropathological diagnosis. Like several other AD biomarkers, FDG PET has the potential to accelerate the evaluation of AD-modifying treatments, particularly in the earliest clinical and preclinical stages. This article considers FDG PET's role in the detection and tracking of AD, its emerging roles in the evaluation of disease-slowing treatments, some of the issues involved in the acquisition, analysis, and interpretation of FDG PET data, and the evidence needed to help qualify FDG PET and other biomarkers for use in the accelerated approval of AD slowing treatments. It recommends scientific strategies and public policies to further establish the role of FDG PET and other AD biomarkers in therapeutic trials and find demonstrably effective disease-modifying and presymptomatic AD treatments as quickly as possible. PMID- 21983242 TI - Clinical trial methodologies for disease-modifying therapeutic approaches. AB - In recent years, advances in Alzheimer's disease (AD) biomarker research have provided powerful tools to improve trial design. In particular, biomarkers provide powerful methods for the selection of individuals with Alzheimer's disease prior to the onset of dementia. Data suggest that neuroimaging biomarkers will be useful as endpoints for trials in very early, even asymptomatic disease, though further work is necessary to establish validity for regulatory purposes. PMID- 21983243 TI - Development of biofuel cells based on gold nanoparticle decorated multi-walled carbon nanotubes. AB - This study focused on developing the synthesis of Au nanoparticle-decorated functionalized multi-walled carbon nanotubes (Au-NPs/f-MWCNTs) for monosaccharide (bio-fuel) oxidation reactions and practical application in air-biofuel cells. We developed a scalable and straightforward method to synthesize Au-NPs/f-MWCNTs which allow us to control the loading and size of the Au-NPs. The Au-NPs/f-MWCNTs exhibited better catalytic activities and stability than the Au sheet and subsequently resulted in a threefold increase in the power density of the air glucose fuel cell with an exceptionally high open circuit voltage (~1.3 V). The catalytic efficiency was confirmed by high performance liquid chromatography with the superior of the Au-NPs/f-MWCNTs over a bare gold electrode. In addition, the application of this advanced catalyst to other monosaccharide oxidation reactions figured out that the configuration of -OH groups at C(2) and C(3) of the reactants plays an important role in the initial adsorption process, and thus, affects the required activation energy for further oxidation. The different monosaccharides lead to significantly different fuel cell performances in terms of power density, which coherently corresponds to the difference in the configuration of C(2) and C(3). Because two small air-glucose fuel cells using Au NPs/f-MWCNTs can run a LED lamp, further applications of other monosaccharides as fuel in biofuel cells for equivalent required power devices may be possible. PMID- 21983244 TI - Commonalities between the pro-fibrotic mechanisms in COPD and IPF. AB - COPD and IPF are two chronic lung diseases which are characterized by a decline in lung function, resulting in significant morbidity and mortality. Both of these diseases are more commonly associated with an aging population and the duration for which the disease has been underlying is often unknown. Significant matrix deposition occurs, resulting in either non-reversible airways obstruction in the case of COPD and impaired gas exchange and parenchymal consolidation in IPF. There are no approved therapies that have been demonstrated to target these underlying fibrotic changes in the lung. This may in part be due to the challenges of quantitating lung fibrosis in a temporal manner in specific regions of the lung. However, this may also be due to our understanding of aberrant and pathogenic collagen deposition being somewhat limited. The core processes associated with lung fibrosis are often observed in normal wound healing. Moreover, in the extreme fibrotic setting of IPF, the remodelling is sometimes associated with uncontrolled wound healing responses. As wound healing is a critical aspect to maintaining tissue function and homeostasis, targeting this process directly may result in safety concerns. This review therefore describes some of the recent advances in ascertaining pathways promoting lung fibrosis that may be amenable to therapeutic intervention in both COPD and IPF. PMID- 21983245 TI - Potential of two new oximes in reactivate human acetylcholinesterase and butyrylcholinesterase inhibited by organophosphate compounds: an in vitro study. AB - Organophosphate (OP) compounds exert inhibition on cholinesterase (ChE) activity by irreversibly binding to the catalytic site of the enzyme. Oximes are compounds generally used to reverse the ChE inhibition caused by OP agents. In this study, we compared the in vitro reactivation potency of two new oximes (oxime 1: butane 2,3-dionethiosemicarbazone; oxime 2: 3-(phenylhydrazono) butan-2-one) against the inhibition on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities induced by chlorpyrifos, diazinon and malathion. Oximes used clinically (obidoxime and pralidoxime) were used as positive control. For this study, human blood (erythrocytes for AChE determination and plasma for BChE determination) was used and different concentrations of oximes (1-100 MUM) were tested. The concentrations of OP used were based on the IC50 for AChE and BChE. Results demonstrated that obidoxime was more effective in reactivate the AChE inhibition induced by OP compounds. However, both newly developed oximes achieved similar reactivations rates that pralidoxime for chlorpyrifos and diazinon inhibited AChE. For BChE reactivation, none of evaluated oximes achieved positives rates of reactivation, been obidoxime able to reactivate malathion inhibited BChE only in 24% at the highest concentration. We conclude that both newly developed oximes seem to be promising reactivators of OP-inhibited AChE. PMID- 21983248 TI - Intravitreal tissue plasminogen activator to treat refractory diabetic macular edema by induction of posterior vitreous detachment. AB - PURPOSE: To evaluate the effects of intravitreal injection of recombinant tissue plasminogen activator (TPA) for the treatment of refractory diabetic macular edema. METHODS: A total of 27 patients with refractory diabetic macular edema with no evidence of posterior vitreous detachment were randomly assigned into follow-up (F/U) or TPA treatment groups. To control for the effects of intravitreal injection, an additional 14 patients with diabetic macular edema who were candidates for first-time intravitreal bevacizumab injection were enrolled as the IVB group. For the TPA and IVB groups, 25 MUg of TPA or 1.25 mg of bevacizumab, respectively, were intravitreally injected. Fundoscopy, optical coherence tomography, and B-scan ultrasonography were performed at 1 week, 1 month, and 3 months after initiation of the study. RESULTS: The incidence of posterior vitreous detachment in fundoscopy over the follow-up period was 69.2% in the TPA group, which was significantly higher than that of the F/U and IVB groups (P = 0.001). Best-corrected visual acuity and changes in macular thickness did not significantly differ between the TPA and F/U groups over the 3-month period. CONCLUSION: Intravitreal TPA injection induces posterior vitreous detachment in patients with diabetic macular edema refractory to standard treatment but has no effect on macular thickness or best-corrected visual acuity within 3 months. PMID- 21983249 TI - Diagnostic and therapeutic challenges. PMID- 21983250 TI - High-definition spectral-domain optical coherence tomography of intravitreal and subretinal cysticercus cysts in intraocular cysticercosis. PMID- 21983251 TI - Acute haemodynamic changes after percutaneous mitral valve repair: relation to mid-term outcomes. AB - BACKGROUND: Percutaneous mitral valve repair (MVR) using the Evalve MitraClip has been recently introduced as a potential alternative to surgical MVR. OBJECTIVE: To assess immediate haemodynamic changes after percutaneous MVR using right heart catheterisation. Design Single-centre longitudinal cohort study. SETTING: Tertiary referral centre. PATIENTS: Fifty consecutive non-surgical patients (age 74+/-14 years, EuroSCORE 26+/-14) with moderate to severe (3+) and severe (4+) mitral regurgitation (MR) due to functional (56%), degenerative (30%) or mixed (14%) disease were selected. INTERVENTIONS: MitraClip implantation was performed under general anaesthesia with fluoroscopy and echocardiographic guidance. Haemodynamic variables were obtained before and after MVR using standard right heart catheterisation and oximetry. MAIN OUTCOME MEASURES: Haemodynamic changes immediately before and after MVR. RESULTS: Acute procedural success (reduction in MR to grade 2+ or less) was achieved in 46 (92%) patients. Mitral valve clipping reduced mean pulmonary capillary wedge pressure (mPCWP) (from 17+/-7 to 12+/-5 mm Hg), PCWP v-wave (from 24+/-11 to 16+/-7 mm Hg) and mean pulmonary artery pressure (mPAP) (from 29+/-12 to 24+/-6 mm Hg), and increased the cardiac index (CI) (from 3.1+/-1.0 to 3.9+/-1.1 l/min/m(2)) (all p<0.05). On Cox univariate regression analysis, mPCWP, PCWP v-wave- and mPAP-changes were associated with death, open-heart surgery for MR and/or hospitalisation for heart failure on follow-up. CONCLUSION: In a heterogeneous population with predominantly functional MR, percutaneous MVR with the Evalve MitraClip system lowers mPCWP, PCWP v-wave and mPAP by 20%, 20% and 8%, respectively, and increases the CI by 32%. PMID- 21983252 TI - New treatment strategies in advanced neuroendocrine tumours. AB - Malignant well-differentiated neuroendocrine tumours of the pancreas and the gastrointestinal tract are rare and clinically challenging heterogeneous neoplasms. This review focuses on neuroendocrine tumours grade 1 and grade 2 (new WHO classification 2010), in comparison to the neuroendocrine tumours grade 3 group, corresponding to poorly differentiated neuroendocrine carcinomas. Surgical resection of the primary and metastases remains the only curative treatment, however many patients with neuroendocrine tumours are diagnosed once unresectable metastases have occurred; management of functioning syndromes with somatostatin analogues remains the priority. Pasireotide, a new somatostatin analogue, is currently undergoing evaluation for carcinoid syndrome. Treatment options for advanced neuroendocrine tumours differ from pancreatic gastrointestinal tract neuroendocrine tumours: (a) in pancreatic neuroendocrine tumours, streptozotocin based chemotherapies are challenged by other cytotoxic agents (dacarbazine, temozolomide and oxaliplatin); two randomized, placebo-controlled phase III studies have demonstrated that everolimus and sunitinib significantly improved progression-free-survival; (b) in midgut neuroendocrine tumours, octreotide improved time-to-progression in patients with a low proliferation index and low liver burden; preliminary data suggesting efficacy of bevacizumab are still to be confirmed; the effect of everolimus associated with octreotide was almost significant on progression-free-survival in a phase III trial. Liver-directed therapies are effective in both tumour types. New techniques of embolization need further evaluation and must be formally compared to other therapies. Finally, peptide receptor radionuclide therapy has shown promising activity in non comparative studies in advanced neuroendocrine tumours. PMID- 21983253 TI - Evaluation of the performance of the Abbott ARCHITECT HIV Ag/Ab Combo Assay. AB - BACKGROUND: Worldwide, many countries test for HIV infection using combination assays that simultaneously detect p24 antigen and HIV antibodies. One such assay, the ARCHITECT((r)) HIV Ag/Ab Combo Assay (ARCHITECT), has recently been approved by the Food and Drug Administration (FDA) for use in the United States. OBJECTIVE: To evaluate the performance of ARCHITECT on well-characterized specimens from four CDC-funded studies. STUDY DESIGN: We evaluated 3386 HIV infected, 7551 HIV-uninfected, and 58 acute HIV infection (AHI) specimens. HIV infected specimens were repeatedly reactive by enzyme immunoassay (EIA) and Western blot (WB) or positive by nucleic acid amplification testing (NAAT). HIV uninfected specimens were EIA- and NAAT-negative. AHI specimens were seronegative or indeterminate (using antibody-based EIAs, rapid tests or WB) and NAAT positive. All specimens were de-identified and sent to Abbott Diagnostics for testing with ARCHITECT. ARCHITECT test results were compared to original study characterizations and were used to assess overall sensitivity and specificity and also sensitivity for AHI. ARCHITECT false-positive specimens with sufficient quantity were retested. RESULTS: Based on results from the initial ARCHITECT test, sensitivity was 99.94% (95% confidence interval [CI]: 99.79, 99.99) and specificity was 98.78% (95% CI: 98.51-99.01). Repeat testing resulted in corrected specificity of 99.50% (95% CI: 99.31, 99.64). Also, 48 AHI specimens (83%) were detected by this screening assay. CONCLUSION: The sensitivity and specificity of the ARCHITECT combination assay are very high and most AHIs were detected by the assay. Use of Ag/Ab combination assays may improve the number of AHIs identified relative to existing FDA-approved HIV-antibody only based serologic assays, particularly in high incidence populations. PMID- 21983254 TI - Use of a rapid HIV testing algorithm to improve linkage to care. AB - BACKGROUND: Awaiting definitive diagnosis before scheduling healthcare visits complicates HIV screening and referral. Clients screened by rapid tests as initially reactive often fail to return to receive definitive test results, are not linked to care and enter care late or not at all. OBJECTIVES: To evaluate statewide, (1) the accuracy of a single-visit, two test HIV rapid testing algorithm (RTA) and (2) its effect on referral to care for positive clients. STUDY DESIGN: A two-test RTA was implemented at 24 sites in New Jersey beginning in December 2008. All clients with a reactive rapid HIV test were offered a second rapid HIV test, and RTA results were compared with Western blot (WB). Referral to care occurred based upon two sequential positive rapid tests. RESULTS: The RTA program has screened 51,413 individuals obtaining 426 reactive rapid test results; 394 (92.5%) were reactive by a second rapid test, 32 (7.5%) had a negative second rapid test. Twenty-eight individuals refused WB testing. Of 369 RTA-positive individuals who have WB results, 368 (99.5%) were confirmed positive. Of RTA-positive clients, 290 (73.6%), including 25 (6.6%) who refused Western blot, were immediately referred for care including one individual with a false-positive RTA. CONCLUSIONS: The RTA reduced false positive results by 6.2% and agreed with WB results 99.5% of the time. Improved referral to care compared to traditional rapid HIV screening occurs when immediate referral is based on RTA verification of a preliminary positive rapid test. WB confirmation is not essential for effective screening and contributes to difficulties linking individuals to care. PMID- 21983255 TI - Pseudomorphy, surface alloys and the role of elementary clusters on the domain orientations in the Cu/Al13Co4(100) system. AB - We have used the pseudo-tenfold surface of the orthorhombic Al(13)Co(4) crystal as a template for the adsorption of Cu thin films of various thicknesses deposited at different temperatures. This study has been carried out by means of low energy electron diffraction (LEED), scanning tunnelling microscopy (STM), x ray photoelectron spectroscopy (XPS) and x-ray photoelectron diffraction (XPD). From 300 to 573 K, Cu adatoms grow pseudomorphically up to one monolayer. At 300 K, the beta-Al(Cu, Co) phase appears for coverages greater than one monolayer. For higher temperature deposition, the beta-Al(Cu, Co) phase further transforms into the gamma-Al(4)Cu(9) phase. Both beta and gamma phases grow as two (110) domains rotated by 72 degrees +/- 1 degrees from each other. Instead of following the substrate symmetry, it is the orientations of the bipentagonal motifs present on the clean Al(13)Co(4)(100) surface that dictate the growth orientation of these domains. The initial bulk composition and structural complexity of the substrate have a minor role in the formation of the gamma Al(4)Cu(9) phase as long as the amount of Al and the Cu film thickness reach a critical stoichiometry. PMID- 21983256 TI - Evidence for aluminum-binding erythropoietin by size-exclusion chromatography coupled to electrothermal absorption atomic spectrometry. AB - Erythropoietin (EPO) is a glycoprotein that stimulates erythropoiesis and is clinically used for treating anemia during chronic renal failure and for anemia in preterm infants. EPO formulations usually have elevated rates of contamination due to aluminum (Al), which is toxic to both types of patients. Size-exclusion chromatography (SEC) coupled with graphite furnace atomic absorption spectrometry (GF AAS) was employed to separate proteins and to quantify the amount of aluminum present in the elution volume corresponding to EPO and, therefore, to evaluate possible binding. Because EPO formulations contain human serum albumin (HSA), a chromatographic method was optimized for the separation of these proteins. Subsequent to the chromatographic separation, 1-mL fractions of the column effluent were collected, and the Al content in these aliquots was measured by GF AAS. EPO and HSA samples were incubated with Al for 4h at 4 degrees C and 37 degrees C as well as for 16 h at 4 degrees C and 37 degrees C. Afterwards, they were injected into the chromatographic system. These samples were also submitted to ultrafiltration (10 and 50 kDa membranes), and Al was measured in the ultrafiltrates. The results showed that Al was present in the eluent volume corresponding to the EPO peak but not in the HSA peak in the chromatograms. Temperature strengthened the interaction because the Al present in the EPO fraction was 3 times higher at 37 degrees C compared to 4 degrees C. Thirty-eight percent of the Al present in a 2.4 MUg/mL EPO standard solution, and approximately 50% of the Al in formulation samples containing approximately 11 MUg/mL EPO and either citrate or phosphate, were non-ultrafiltrable, which suggests that EPO is an effective Al acceptor in vitro. PMID- 21983257 TI - Fluorescence characterization of the interaction Suwannee river fulvic acid with the herbicide dichlorprop (2-(2,4-dichlorophenoxy)propionic acid) in the absence and presence of aluminum or erbium. AB - This study uses fluorescence spectroscopy to better understand the role of environmental metal ions in the interaction of charged herbicides with biochemical degradation product Suwannee River fulvic acid (SRFA). The interactions between the widely-used herbicide dichlorprop (2-(2,4 dichlorophenoxy)propionic acid) (DCPPA) with Al(3+) and the comparative metal Er(3+) were probed at pH 4.0. Fluorescence experiments on binary solutions at pH 4.0 clearly indicated that Al(3+) and Er(3+) strongly interact with both SRFA and DCPPA alone in solution as demonstrated by fluorescence quenching with DCPPA and enhancement with SRFA by Al(3+) and fluorescence quenching of both SRFA and DCPPA fluorescence by Er(3+). Titrating Al(3+) or Er(3+) to SRFA-DCPPA quenched SRFA fluorescence as compared to the SRFA-metal ion binary complexes. Formation constants were determined using the Ryan-Weber model for the titration data. The DCPPA fluorescence results strongly support the formation of DCPPA-Al(3+) and DCPPA-Er(3+) complexes at pH values above the pK(a) (3.0) of DCPPA. Excitation and emission data obtained on ternary solutions of SRFA-Al(3+)-DCPPA and SRFA Er(3+)-DCPPA complexes at pH 4.0 suggest that at this pH where the predominant DCPPA species is negatively-charged, Al(3+) and Er(3+) metal ions may function to "bridge" negatively-charged fulvic acids to negatively-charged pesticides. Fluorescence data collected on UV-irradiated ternary complexes indicate that both metals can also bridge DCPPA interactions with SRFA under those conditions. The results of our studies suggest that creation of a herbicide-free boundary corridor is recommended near mines and runoff areas with metal ions in surface waters to control possible complexation among fulvic acids, DCPPA and metal ions that maintains these molecules in a bioavailable state to plants and animals. PMID- 21983258 TI - The standard electrode potential (Etheta) predicts the prooxidant activity and the acute toxicity of metal ions. AB - The standard electrode potential (E(theta)) has been known for many decades to predict the toxicity of metal ions. We have compiled acute toxicity data from fifteen studies and find that the toxicity of thirty metal ions correlates with E(theta) at r(2)=0.868 when toxicity is expressed as log concentration of comparably effective doses. We have discovered an even stronger relationship between the prooxidant activity (PA) of metal ions and E(theta) (and electronegativity, chi). Data compiled from thirty-four studies demonstrate that the PA of twenty-five metal ions correlates with E(theta) at r(2)=0.983 (and chi at r(2)=0.968). PA was commonly measured as metal-induced peroxidation of cell membranes or accumulation of reactive oxygen species. None of the redox metals (capable of Fenton-like reactions) in our studies (i.e., Mn, Fe, Co, Ni, and Cu) was prooxidative or toxic beyond what was expected from E(theta) or chi. We propose that the formation of superoxide-metal ion complexes is greater at greater E(theta) or chi values and that these complexes, whether free or enzyme bound, function in PA without redox cycling of the complexed ion. PMID- 21983259 TI - African horse sickness virus induces apoptosis in cultured mammalian cells. AB - Infection of mammalian cell cultures with African horse sickness virus (AHSV) is known to result in dramatic cytopathic effects (CPE), but no CPE is observed in infected insect cell cultures despite productive virus replication. The basis for this phenomenon has not yet been investigated, but is suggestive of apoptosis being induced following virus infection of the mammalian cells. To investigate whether AHSV can induce apoptosis in infected mammalian cells, Culicoides variipennis (KC) insect cells and BHK-21 mammalian cells were infected with AHSV 9 and analyzed for morphological and biochemical hallmarks of apoptosis. In contrast to KC cells, infection of BHK-21 cells with AHSV-9 resulted in ultrastructural changes and nuclear DNA fragmentation, both of which are associated with the induction of apoptosis. Results also indicated that AHSV-9 infection of BHK-21 cells resulted in activation of caspase-3, a key agent in apoptosis, and in mitochondrial membrane depolarization. Cumulatively, the data indicate that the intrinsic pathway is activated in AHSV-induced apoptosis. PMID- 21983260 TI - Effects of antinutrient proteins on Hessian fly (Diptera: Cecidomyiidae) larvae. AB - One strategy to enhance the durability of Hessian fly resistance (R) genes in wheat is to combine them with transgenes for resistance. To identify potential transgenes for resistance a protocol for rapidly screening the proteins they encode for efficacy toward resistance is required. However, the Hessian fly is an obligate parasite of wheat and related grasses. Consequently, no protocol for in vitro delivery of antinutrient or toxic proteins to feeding larvae is available. We report here the development of a Hessian fly in plantatranslocation (HIT) feeding assay and the evaluation of eight lectins and the Bowman-Birk serine proteinase inhibitor for potential in transgenic resistance. Of the antinutrient proteins evaluated, Galanthus nivalis L. agglutinin (GNA), commonly termed snowdrop lectin, was the most efficacious. Ingestion of GNA caused a significant reduction in growth of Hessian fly larvae, disruption of midgut microvilli, and changes in transcript level of genes involved in carbohydrate metabolism, digestion, detoxification, and stress response. These effects of GNA are discussed from the perspective of larval Hessian fly physiology. PMID- 21983261 TI - Creutzfeldt-Jakob disease with the M232R mutation in the prion protein gene in two cases showing different disease courses: a clinicopathological study. AB - We report two autopsy cases of Creutzfeldt-Jakob disease (CJD) with the M232R mutation of the prion protein (PrP) gene that exhibited different clinicopathological features (age at death, 64/54 years; disease duration, 13/26 months). Both cases showed myoclonus, hyperintensity on diffusion-weighted MRI, and increased 14-3-3 protein in the cerebrospinal fluid. The initial sign in each case was memory disturbance and abnormal pharyngeal sensation, respectively. In the first case, the disease progressed rapidly with akinetic mutism developing 6 months after onset, while it occurred 23 months after onset in the second case. Pathologically, both cases had severe neuronal loss with gliosis and spongiform change in the cerebral cortex, basal ganglia, and cerebellum. PrP deposition was the diffuse synaptic type in the first case, but the second case had both diffuse synaptic and perivacuolar types. PrP(sc) immunoblotting revealed a type 1 band pattern in the first case, but both types 1 and 2 in the second case. Based on these findings, together with the results in previous CJD cases with M232R, we noted the possibility that the presence of type 2 PrP(sc) may be associated with both morphological features of PrP deposition and slow disease progression in this genetic prion disease. PMID- 21983262 TI - Solid state amorphization kinetic of alpha lactose upon mechanical milling. AB - It has been previously reported that alpha-lactose could be totally amorphized by ball milling. In this paper we report a detailed investigation of the structural and microstructural changes by which this solid state amorphization takes place. The investigations have been performed by Powder X-ray Diffraction, Solid State Nuclear Magnetic Resonance ((13)C CP-MAS) and Differential Scanning Calorimetry. The results reveal the structural complexity of the material in the course of its amorphization so that it cannot be considered as a simple mixture made of a decreasing crystalline fraction and an increasing amorphous fraction. Heating this complexity can give rise to a fully nano-crystalline material. The results also show that chemical degradations upon heating are strongly connected to the melting process. PMID- 21983263 TI - Behavioral and neurobiological characteristics of social stress versus depression in nonhuman primates. AB - The focus of the review is on the behavioral and physiological manifestations of stress versus depression. The purpose of the review is to evaluate the conceptual approach of using stress models as surrogates for depression. Social stress and depression have many characteristics in common and promote each other. Both have adverse effects on social relationships and the quality of life, and increase risk of other diseases. However, they are not the same constructs. In human and nonhuman primates, the behavior and neurobiology of stressed individuals differ from that of depressed individuals. Some similarities in stress physiology in socially stressed and depressed individuals have been used to support the use of stressed animals as models of depression, and much has been learned from stress models of depression. However, the studies reviewed here also suggest that the depressed state also has different characteristics than the stressed state, and studying the differences may be important to furthering our understanding of each of these constructs as well as their mutual relationship. PMID- 21983264 TI - Direct and indirect anticancer activity of bisphosphonates: a brief review of published literature. AB - The bone marrow microenvironment provides a site for cancer cells to evade systemic anticancer therapy. Dormant tumor micrometastases are believed to be the source of disease persistence and relapse; however, the exact characteristics of cancer stem cells vs. cancer cells with limited metastatic potential have yet to be elucidated. Bisphosphonates inhibit osteoclast-mediated bone resorption, are approved for treating malignant bone disease from advanced cancers, and have shown efficacy for preventing cancer treatment-induced bone loss. Altering the bone marrow microenvironment to make it less conducive to cancer cell survival is now emerging as an important means to prevent cancer recurrence. This review aims to distill the diverse literature and provide a brief overview of the numerous preclinical and early clinical studies of bisphosphonates demonstrating a variety of direct and indirect anticancer activities that affect both the tumor cell (the "seed") and surrounding microenvironment (the "soil"). Recently, zoledronic acid was found to improve disease-free survival and overall survival in some adjuvant breast cancer settings and prolonged survival in patients with multiple myeloma and other advanced cancers. In the prostate cancer setting, antiresorptive therapy was reported to delay the development of overt bone metastases. Ongoing studies will provide further insight regarding the anticancer potential of bisphosphonates and other antiresorptive agents. PMID- 21983265 TI - A spicamycin derivative (KRN5500) provides neuropathic pain relief in patients with advanced cancer: a placebo-controlled, proof-of-concept trial. AB - CONTEXT: Neuropathic pain in patients with cancer can be difficult to treat effectively. OBJECTIVES: The purpose of the study was to determine safety and efficacy of KRN5500, a novel, spicamycin-derived, nonopioid analgesic agent, in patients with advanced cancer and neuropathic pain of any etiology. METHODS: The study was a Phase 2a, multicenter, double-blind, placebo-controlled, dose escalation clinical trial. Patients with refractory neuropathic pain and advanced cancer were randomly assigned 2:1 to receive a maximum of eight single escalating doses of KRN5500 or placebo, ranging from 0.6 to 2.2 mg/m(2). The primary objective was safety and tolerability. The secondary objective was efficacy, measured by change in average pain intensity on a 0-10 numeric rating scale administered one week after the patient's final dose. RESULTS: Nineteen patients received treatment (KRN5500 n=12; placebo n=7). The most frequently reported adverse events were gastrointestinal symptoms, which were more frequent and severe with KRN5500 than placebo; two (17%) KRN5500 patients discontinued the study because of nausea and vomiting. At study endpoint, KRN5500 exhibited a significant median decrease in pain intensity from baseline of 24% compared with 0% for placebo (P=0.03). The median for largest weekly reduction in target pain intensity was 29.5% for KRN5500 and 0% for placebo patients (P=0.02). CONCLUSION: This proof-of-concept study for KRN5500 in patients with advanced cancer and any type of neuropathic pain found gastrointestinal adverse events to be the predominant safety concern. The results also provided the first indication of clinical and statistical efficacy in reducing pain intensity. PMID- 21983266 TI - Magnesium intake is associated with strength performance in elite basketball, handball and volleyball players. AB - Magnesium plays significant roles in promoting strength. Surveys of athletes reveal that intake of magnesium is often below recommended levels. We aimed to understand the impact of magnesium intake on strength in elite male basketball, handball, and volleyball players. Energy and nutrient intake were assessed from seven-day diet record. Strength tests included maximal isometric trunk flexion, extension, and rotation, handgrip, squat and countermovement Abalakov jump, and maximal isokinetic knee extension and flexion peak torques. Linear regression models were performed with significance at p<0.1. Mean magnesium intake was significantly lower than the recommended daily allowance. Regression analysis indicated that magnesium was directly associated with maximal isometric trunk flexion, rotation, and handgrip, with jumping performance tests, and with all isokinetic strength variables, independent of total energy intake. The observed associations between magnesium intake and muscle strength performance may result from the important role of magnesium in energetic metabolism, transmembrane transport and muscle contraction and relaxation. PMID- 21983267 TI - Interpersonal emotion regulation as a mechanism of social support in depression. AB - Although social support is widely considered to be protective against depression, the mechanisms through which it acts on depressive psychopathology are not well known. This integrative review argues that emotion regulation serves as such a mechanism. First, the literature on the effects of social support on depression is reviewed, with an emphasis on open empirical questions regarding mechanisms linking support and depression. Then, the literature on emotion regulation is reviewed, highlighting its importance as a mechanism in the psychopathology of depression. Finally, potential interpersonal influences on depressive emotion regulation and dysregulation are suggested, drawing from theory and research on psychotherapy and on close relationships. The review suggests that emotion regulation is responsive to interpersonal influences, and that this responsiveness may account for the effects of social support on depression. Implications of an interpersonal perspective for basic and clinical research on depression, close relationships, and emotion regulation are discussed. PMID- 21983268 TI - SOX9 regulates endocrine cell differentiation during human fetal pancreas development. AB - The transition of pancreatic progenitor cells to mature endocrine cells is regulated by the sequential activation and interaction of several transcription factors. In mice, the transcription factor Sox9 has been shown to support endocrine cell differentiation. However, the functional role of SOX9 during pancreas development in the human has yet to be determined. The present study was to characterize SOX9 expression during human fetal pancreas development and examine its functional role by transfection with SOX9 siRNA or SOX9 expression vectors. Here we report that SOX9 was most frequently expressed in PDX1(+) cells (60-83%) and least in mature endocrine cells (<1-14%). The proliferation of SOX9(+) cells was significantly higher at 8-10 weeks than at 14-21 weeks (p<0.05) or 20-21 weeks (p<0.01). SOX9 frequently co-localized with FOXA2, NGN3 and transcription factors linked to NGN3 (NKX2.2, NKX6.1, PAX6). siRNA knockdown of SOX9 significantly decreased islet-epithelial cell proliferation, NGN3, NKX6.1, PAX6 and INS mRNA levels and the number of NGN3(+) and insulin(+) cells (p<0.05) while increasing GCG mRNA and glucagon(+) cells (p<0.05). Examination of SOX9 associated signaling pathways revealed a decrease in phospho-Akt (p<0.01), phospho-GSK3beta (p<0.01) and cyclin D1 (p<0.01) with a decrease in nuclear beta catenin(+) (p<0.05) cells following SOX9 siRNA knockdown. In contrast, over expression of SOX9 significantly increased the number of islet cells proliferating, NGN3, NKX6.1, PAX6 and INS mRNA levels, the phospho-Akt/GSK3beta cascade and the number of insulin(+) cells. Our results demonstrated that SOX9 is important for the expression of NGN3 and molecular markers of endocrine cell differentiation in the human fetal pancreas. PMID- 21983269 TI - A variational principle for computing nonequilibrium fluxes and potentials in genome-scale biochemical networks. AB - We derive a convex optimization problem on a steady-state nonequilibrium network of biochemical reactions, with the property that energy conservation and the second law of thermodynamics both hold at the problem solution. This suggests a new variational principle for biochemical networks that can be implemented in a computationally tractable manner. We derive the Lagrange dual of the optimization problem and use strong duality to demonstrate that a biochemical analogue of Tellegen's theorem holds at optimality. Each optimal flux is dependent on a free parameter that we relate to an elementary kinetic parameter when mass action kinetics is assumed. PMID- 21983270 TI - Sugarcane improvement: how far can we go? AB - In recent years, efforts to improve sugarcane have focused on the development of biotechnology for this crop. It has become clear that sugarcane lacks tools for the biotechnological route of improvement and that the initial efforts in sequencing ESTs had limited impact for breeding. Until recently, the models used by breeders in statistical genetics approaches have been developed for diploid organisms, which are not ideal for a polyploid genome such as that of sugarcane. Breeding programs are dealing with decreasing yield gains. The contribution of multiple alleles to complex traits such as yield is a basic question underlining the breeding efforts that could only be addressed by the development of specific tools for this grass. However, functional genomics has progressed and gene expression profiling is leading to the definition of gene networks. The sequencing of the sugarcane genome, which is underway, will greatly contribute to numerous aspects of research on grasses. We expect that both the transgenic and the marker-assisted route for sugarcane improvement will contribute to increased sugar, stress tolerance, and higher yield and that the industry for years to come will be able to rely on sugarcane as the most productive energy crop. PMID- 21983271 TI - [Hemoperfusion with polymyxin B in septic shock secondary to Klebsiella pneumoniae induced liver abscesses]. PMID- 21983272 TI - Analysis, occurrence, and function of 9-cis-retinoic acid. AB - Metabolic conversion of vitamin A (retinol) into retinoic acid (RA) controls numerous physiological processes. 9-cis-retinoic acid (9cRA), an active metabolite of vitamin A, is a high affinity ligand for retinoid X receptor (RXR) and also activates retinoic acid receptor (RAR). Despite the identification of candidate enzymes that produce 9cRA and the importance of RXRs as established by knockout experiments, in vivo detection of 9cRA in tissue was elusive until recently when 9cRA was identified as an endogenous pancreas retinoid by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology. This review will discuss the current status of the analysis, occurrence, and function of 9cRA. Understanding both the nuclear receptor-mediated and non-genomic mechanisms of 9cRA will aid in the elucidation of disease physiology and possibly lead to the development of new retinoid-based therapeutics. This article is part of a Special Issue entitled Retinoid and Lipid Metabolism. PMID- 21983273 TI - Suppression of retinol-binding protein 4 with RNA oligonucleotide prevents high fat diet-induced metabolic syndrome and non-alcoholic fatty liver disease in mice. AB - Conflicting data have been reported regarding the role of retinol-binding protein (RBP4) in insulin resistance, obesity, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). In this study, we used pharmacological methods to investigate the role of RBP4. RNA oligonucleotide against RBP4 (anti-RBP4 oligo) was transfected into 3T3-L1 adipocytes. RT-PCR analysis showed that RBP4 mRNA expression decreased by 55% (p<0.01) compared with control cells. Validated RNA oligo was used in an in vivo study with high fat diet (HFD) fed - mice. 14 weeks of HFD feeding increased RBP4 expression (associated with elevated serum levels measured with immunoblotting and ELISA) by 56% in adipose tissue (p<0.05) and 68% in the liver (p<0.01). Adipose RBP4 levels were significantly reduced after 4 weeks treatment with anti-RBP4 oligo (25mg/kg, p<0.01) and rosiglitazone (RSG, 10mg/kg, p<0.05) compared with scrambled RNA oligo (25mg/kg) treated mice. Only anti-RBP4 oligo significantly inhibited RBP4 protein (p<0.01) and mRNA expression (p<0.01) in the liver and reduced serum RBP4 levels. Anti-RBP4 oligo and RSG showed comparable effects on impaired glucose tolerance, hyperinsulinaemia and hyperglycaemia. Anti-RBP4 oligo significantly enhanced adipose-GLUT4 expression (p<0.01) but did not increase muscle-GLUT4. Both RSG and anti-RBP4 oligo significantly reduced hepatic phosphoenolpyruvate carboxykinase expression (both p<0.05). Histological analysis revealed that anti-RBP4 oligo ameliorated hepatic steatosis and reduced lipid droplets associated with normalized liver function. Histological and pharmacological results of this study indicate that RBP4 is not only an adipocytokine, but also a hepatic cytokine leading to metabolic syndrome, NAFLD and type 2 diabetes. PMID- 21983275 TI - Acute toxicity bioassay of mercury and silver on Capoeta fusca (black fish). AB - Since toxicity is based on the effect that a toxicant produces at a target site within an organism, establishing the relationship between the concentration of substance at the target site and the subsequent toxic effect can provide a tool for predicting toxicity. The behavior of a single toxicant could not be fully understood without the knowledge of the fact the physical and biochemical properties of substances that can change. To understand this, the acute toxicity of mercury (as HgSO4) and silver (as AgSO4) to Capoeta fusca (6 treatments in triplicate) was determined. During September 2009, C. fusca belonging to the family Cyprinidae, weighing 2.95 (+/-0.55) g, were obtained from qanats in Birjand, East of Iran. The fish were maintained in an aquarium system at a holding temperature of 21 (+/-0.2) and were allowed to adjust to lab conditions for 1 week before experimentation. The lethal concentration 50 (LC50) values for HgSO4 at 24, 48, 72, and 96 h of exposure were 0.32, 0.28, 0.26, and 0.24 mg L-1, respectively. Also, the LC50 values for AgSO4 at 24, 48, 72, and 96 h of exposure were 0.014, 0.013, 0.013, and 0.013 mg L-1, respectively. Results of this study showed that C. fusca was very sensitive to AgSO4. PMID- 21983276 TI - Toxic impact of two organophosphate insecticides on biochemical parameters of a food fish and assessment of recovery response. AB - Sublethal effects of chlorpyrifos (CPF) and monocrotophos (MCP) on fish biochemical constituents were investigated along with the assessment of recovery response after cessation of intoxication. The fish, Clarias batrachus were exposed to 1.656 mg(-l) and 2.114 mg(-l) of CPF and MCP for 28 days. After 28 days, they were released in freshwater and allowed to recover for 21 days. The CPF exposure resulted in the decrease of carbohydrate and glycogen content, whereas MCP intoxication caused mixed response. Pyruvate and lactate contents were altered under the stress of CPF and MCP. Recovery of these alterations was observed after the cessation of toxicity. Exposure of C. batrachus to CPF and MCP resulted in decreased activity of lactate dehydrogenase in the kidney, liver and muscle but its activity increased in the gills. The CPF caused inhibition of succinate dehydrogenase enzyme in all tissues. Induction in the activity of malate dehydrogenase was caused by both insecticides. Glycogen phosphorylase a was induced in all tissues, whereas glycogen phosphorylase ab showed both induction and inhibition. Of the two insecticides, CPF was more toxic and the recovery response was less. These results are important in the assessment of the risk caused by organophosphate insecticides on nontarget organisms, especially the food fish. PMID- 21983277 TI - Psychosis and Dandy-Walker complex: report of four cases. AB - Concurrence of psychosis and Dandy-Walker complex (DWC) has been reported in some medical literature. Here, we reported four patients with concurrent psychosis and DWC of all four subtypes. Some clinical features found were juvenile or young adult age onset, high frequency of family history of psychosis, atypical psychotic symptoms, and high prevalence of cognitive deficit and refractoriness to treatment, in line with the cases in previous reports. These findings might help further illuminate the role that the cerebellum plays in the etiology of schizophrenia or bipolar disorder. PMID- 21983278 TI - Central metabolite changes and activation of microglia after peripheral interleukin-2 challenge. AB - Interleukin (IL)-2 regulates the immune response through the proliferation of activated T-cells and also exerts effects on the central nervous system (CNS). Alongside having marked neurobehavioral effects, IL-2 has been suggested to impact on various psychiatric disorders. The immune-CNS communication of IL-2 remains unclear, although, it is suggested that microglia are the source and target of IL-2. Here, we analyzed changes in brain metabolites following a peripheral IL-2 challenge and examined the contribution of microglia in mediating these effects. Rats were assessed by magnetic resonance spectroscopy (MRS) in a 9.4 T scanner for baseline metabolite levels in the prefrontal cortex (PFC) and the hippocampus. After 7 days animals were scanned again following a single injection of IL-2 (2.5 MUg/kg) and then tested on the elevated plus-maze for the correlation of IL-2-induced brain metabolites and measures of anxiety. In another experiment CD25(+) microglia cells were determined. A separate group of rats was injected either with IL-2 or vehicle, and afterward the PFC and hippocampus were dissected and fluorescence activated cell sorting (FACS) analysis was performed. The MRS scans in the intra-individual study design showed a significant increase in myo-inositol in the analyzed regions. A significant correlation of anxiety like measures and myo-inositol, a marker for microglia activity, was found in the hippocampus. The FACS analysis showed a significant increase in CD25(+) microglia in the hippocampus compared to controls. The results support the role of microglia as a mediator in the immune-CNS communication and the effects of peripheral IL-2. PMID- 21983279 TI - Adult murine hippocampal neurogenesis is inhibited by sustained IL-1beta and not rescued by voluntary running. AB - Acute neuroinflammation reduces adult hippocampal neurogenesis but the role of chronic neuroinflammation, which may be more representative of ongoing processes in CNS disorders, remains relatively unknown. Interleukin-1beta (IL-1beta) is a pro-inflammatory cytokine that has been shown to acutely impair neurogenesis. To further investigate the relationship between sustained IL-1beta expression and adult neurogenesis, a mouse model with an IL-1beta excisionally activated transgene, IL-1beta(XAT), was utilized. Upon exposure to Cre recombinase, IL 1beta overexpression in this model results in chronic neuroinflammation, which persists up to 12 months and causes glial activation, cellular recruitment, and deficits in learning and memory. We hypothesized that adult neurogenesis would be reduced by sustained hippocampal IL-1beta overexpression and rescued by voluntary running, which has been shown to enhance neurogenesis. Hippocampal inflammation in the IL-1beta(XAT) model severely impaired doublecortin (DCX) positive cells at 1 and 3 months after IL-1beta induction. Furthermore, BrdU labeling demonstrated a shift in cell lineage from neuronal to astroglial in the context of sustained hippocampal IL-1beta overexpression. Deletion of the IL-1 receptor prevented the decrease in DCX(+) cells. Voluntary running did not attenuate the effects of IL 1beta expression demonstrated by DCX staining. These results suggest that chronic neuroinflammation severely impairs adult hippocampal neurogenesis and voluntary running is not beneficial as a therapy to rescue these effects. PMID- 21983280 TI - Type D personality and course of health status over 18 months in outpatients with heart failure: multiple mediating inflammatory biomarkers. AB - BACKGROUND: The distressed (Type D) personality is associated with poor health status (HS) and increased inflammatory activation in heart failure (HF). We tested whether multiple inflammatory biomarkers mediated the association between Type D personality and the course of self-reported HS over 18 months. METHODS: HF outpatients (n=228, 80% male, mean age 67.0+/-8.7 years), filled out the Type D questionnaire (DS14) at inclusion and the Short Form-12 (SF12) and the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 0, 6, 12, and 18 months. Blood samples at inclusion were analyzed for high sensitive C-reactive protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and its soluble receptors (sTNFr1, sTNFr2). A multiple mediation latent growth model was tested using structural equation modeling. RESULTS: Type D personality (prevalence=21%) was associated with poorer HS (all scales p<0.001), deterioration of mental HS (p<0.001), and higher TNF-alpha and sTNFr2 levels in the full mediation model. A higher inflammatory burden was associated with a poorer baseline level and a deterioration of generic physical, mental and disease-specific HS. No mediating effects were found for the multiple inflammatory biomarkers on the association between Type D and baseline self-reported HS, whereas change in physical HS was significantly mediated by the group of five inflammatory biomarkers (p=0.026). CONCLUSIONS: Only the association between Type D personality and change in self reported physical health status was significantly mediated by inflammatory biomarkers. Future research should investigate whether the association between Type D personality and poor health status may be explained by other biological or behavioral factors. PMID- 21983281 TI - Early and late components of feed-forward postural adjustments to predictable perturbations. AB - OBJECTIVES: The purpose was to investigate two types of feed-forward postural adjustments associated with preparation to predictable external perturbations. METHODS: Nine subjects stood on a wedge, toes-up or toes-down while a pendulum impacted their shoulders. EMGs of leg and trunk muscles were analyzed within the framework of the uncontrolled manifold hypothesis. RESULTS: Early postural adjustments (EPAs) were seen 400-500 ms and anticipatory postural adjustments (APAs), 100-150 ms prior to the impact. EPAs and APAs were also seen in the time profiles of muscle modes representing muscle groups with linear scaling of the activation levels. Center of pressure shifts were stabilized by co-varied adjustments in muscle mode magnitudes across trials. The index of these multi muscle synergies showed two drops (anticipatory synergy adjustments, ASAs), prior to EPA and APA in each subject. The findings were consistent between the two conditions. CONCLUSIONS: The results show that feed-forward postural adjustments represent a sequence of two phenomena, EPAs and APAs. Each of those is preceded by ASAs that reduce stability of a variable that is to be adjusted during the EPAs and APAs. The findings fit a hierarchical scheme with synergic few-to-many mappings at each level of the hierarchy based on the referent body configuration hypothesis. SIGNIFICANCE: The results show the complexity of the postural preparation to action. Potentially, they have implications for the current strategies of rehabilitation of patients with neuro-motor disorders characterized by impaired postural control. PMID- 21983283 TI - Targeted delivery of small interfering RNA to angiogenic endothelial cells with liposome-polycation-DNA particles. AB - Angiogenesis is an attractive target for cancer therapy, due to its central position in tumor growth and development. Vascular Endothelial Growth Factor (VEGF) and its receptors (VEGFRs) play a key role in the angiogenic process. A promising strategy for targeting VEGF-mediated angiogenesis is RNA interference (RNAi) using short interfering RNA (siRNA). However, for efficacious RNAi a well designed siRNA delivery system is crucial. Liposome-Polycation-DNA (LPD) particles form a promising system for siRNA delivery to tumors. In order to target angiogenic endothelial cells, LPD particles may be modified with a targeting ligand, such as a cyclic Arg-Gly-Asp (RGD) peptide that specifically binds to integrins expressed on tumor-associated endothelial cells. In the current study, RGD-targeted PEGylated LPD particles containing VEGFR-2 siRNA were prepared and optimized with respect to their size and charge by varying protamine content, carrier DNA content for stronger complexation, and PEGylation density. The size of the optimized particles was around 200 nm and the zeta-potential was approximately +20 mV. The uptake and silencing efficacy of the RGD-targeted PEGylated LPD particles were evaluated in H5V cells (murine endothelial cells) and Human Umbilical Vein Endothelial cells (HUVECs). When compared to non targeted LPD particles, enhanced uptake and silencing of VEGFR-2 expression was observed for RGD-targeted PEGylated LPD particles. In conclusion, the RGD targeted PEGylated LPD particles containing VEGFR-2 siRNA presented here may be a promising approach for targeting VEGF-mediated angiogenesis in cancer therapy. PMID- 21983284 TI - E-selectin as a target for drug delivery and molecular imaging. AB - E-selectin, also known as CD62E, is a cell adhesion molecule expressed on endothelial cells activated by cytokines. Like other selectins, it plays an important part in inflammation and in the adhesion of metastatic cancer cells to the endothelium. E-selectin recognizes and binds to sialylated carbohydrates present on the surface proteins of certain leukocytes. E-selectin has been chosen as a target for several therapeutic and medical imaging applications, based on its expression in the vicinity of inflammation, infection or cancer. These systems for drug delivery and molecular imaging include immunoconjugates, liposomes, nanoparticles, and microparticles prepared from a wide range of starting materials including lipids, synthetic polymers, polypeptides and organo metallic structures. After a brief introduction presenting the selectin family and their implication in physiology and pathology, this review focuses on the formulation of these new delivery systems targeting E-selectin at a molecular level. PMID- 21983285 TI - [Citrate regional anticoagulation in continuous renal replacement therapy techniques]. PMID- 21983286 TI - [The symptoms of autism spectrum disorders in the first two years of life: a review of longitudinal prospective studies]. AB - The prospective longitudinal studies of infant siblings of children with Autism Spectrum Disorders (ASD) are revolutionising our understanding of the disorder, offering us the opportunity to examine its development in detail from birth. In this paper we will present a detailed summary of the early symptoms that characterise children with autism from birth to two years of age. The description of the symptoms description will be based on the data from longitudinal prospective studies of children with ASD published to date. The review will conclude with research employing retrospective methodologies. We will discuss the ASD symptoms reviewing those in the first and second year separately, as well as the onset patterns of the disorder. We will highlight those symptoms that allow us to differentiate ASD from other developmental disabilities. ASD are defined by a constellation of symptoms. Studies did not find any differences between ASD and typical development at 6 months of age. The data show that the earliest specific manifestations of ASD are not seen until the end of the first year of life and involve a decreased interest in social stimuli. Other social, communicative, symbolic and in some cases, repetitive and stereotyped interests and behaviours gradually appear in the second year of life, as well as atypical sensorial behaviours. In the second year of life the difficulties in sharing interests with others are noticeable. We will conclude by commenting on the relevance of the data reviewed for the theoretical models explaining autism. PMID- 21983287 TI - Calsequestrin 2 deletion shortens the refractoriness of Ca2+ release and reduces rate-dependent Ca2+-alternans in intact mouse hearts. AB - Calsequestrin (Casq2) is a low affinity Ca(2+)-binding protein located in sarcoplasmic reticulum (SR) of cardiac myocytes. Casq2 acts as a Ca(2+) buffer regulating free Ca(2+) concentration in the SR lumen and plays a significant role in the regulation of Ca(2+) release from this intracellular organelle. In addition, there is experimental evidence supporting the hypothesis that Casq2 also modulates the activity of the cardiac Ca(2+) release channels, ryanodine receptors (RyR2). In this study, Casq2 knockout mice (Casq2-/-) were used as a model to evaluate the effects of the Casq2 on the cytosolic and intra-SR Ca(2+) dynamics, and the electrical activity in the ventricular epicardial layer of intact beating hearts. Casq2-/- mice have accelerated intra-SR Ca(2+) refilling kinetics (76 +/- 22 vs. 136.5 +/- 15 ms) and a reduced refractoriness of Ca(2+) release (182 +/- 32 ms Casq2+/+ and 111 +/- 22 ms Casq2-/- ). In addition, mice display reduced Ca(2+) alternans (67% decline in the amplitude of Ca(2+) alternans at 7 Hz, 21oC) and less T-wave alternans at the electrocardiographic level. The results presented in this paper support the idea of Casq2 acting both as a buffer and a direct regulator of the Ca(2+) release process. Finally, we propose that alterations in Ca(2+) release refractoriness shown here could explain the relationship between Casq2 function and an increase in the risk for ventricular arrhythmias. PMID- 21983288 TI - Occurrence and distribution of hydrocarbons in the surface microlayer and subsurface water from the urban coastal marine area off Marseilles, Northwestern Mediterranean Sea. AB - Aliphatic (AHs) and polycyclic aromatic hydrocarbons (PAHs) were analyzed in dissolved and particulate material from surface microlayer (SML) and subsurface water (SSW) sampled at nearshore observation stations, sewage effluents and harbour sites from Marseilles coastal area (Northwestern Mediterranean) in 2009 and 2010. Dissolved and particulate AH concentrations ranged 0.05-0.41 and 0.04 4.3 MUg l(-1) in the SSW, peaking up to 38 and 1366 MUg l(-1) in the SML, respectively. Dissolved and particulate PAHs ranged 1.9-98 and 1.9-21 ng l(-1) in the SSW, amounting up 217 and 1597 ng l(-1) in the SML, respectively. In harbours, hydrocarbons were concentrated in the SML, with enrichment factors reaching 1138 for particulate AHs. Besides episodic dominance of biogenic and pyrogenic inputs, a moderate anthropisation from petrogenic sources dominated suggesting the impact of shipping traffic and surface runoffs on this urbanised area. Rainfalls increased hydrocarbon concentrations by a factor 1.9-11.5 in the dissolved phase. PMID- 21983289 TI - Is N-sulfation just a gateway modification during heparan sulfate biosynthesis? AB - Several biologically important growth factor-heparan sulfate (HS) interactions are regulated by HS sulfation patterns. However, the biogenesis of these combinatorial sulfation patterns is largely unknown. N-Deacetylase/N sulfotrasferase (NDST) converts N-acetyl-d-glucosamine residues to N-sulfo-d glucosamine residues. This enzyme is suggested to be a gateway enzyme because N sulfation dictates the final HS sulfation pattern. It is known that O-sulfation blocks C5-epimerase, which acts immediately after NDST action. However, it is still unknown whether O-sulfation inhibits NDST action in a similar manner. In this article we radically change conventional assumptions regarding HS biosynthesis by providing in vitro evidence that N-sulfation is not necessarily just a gateway modification during HS biosynthesis. PMID- 21983290 TI - Two non-vesicular ATP release pathways in the mouse erythrocyte membrane. AB - Erythrocytes are exceptionally suited for analysis of non-exocytotic release mechanisms of ATP, because these cells under physiological conditions lack vesicles. Previous studies have indicated, that Pannexin1 (Panx1) provides a key ATP permeation pathway in many cell types, including human and frog erythrocytes. Here we show that erythrocytes of Panx1(-/-) mice lend further support to this conclusion. However, ATP release, although attenuated, was still observed in Panx1(-/-) mouse erythrocytes. In contrast to Panx1(+/+) cells, this release was not correlated with uptake of extracellularly applied dyes, was insensitive to Panx1 channel blockers, and was inhibited by dipyridamole and stimulated by iloprost. Thus, in erythrocytes, two independent pathways mediate the release of ATP. We also show that glyburide is a strong inhibitor of Panx1 channels. PMID- 21983291 TI - Characterization of an optically stimulated dosimeter for dentomaxillofacial dosimetry. AB - OBJECTIVE: The objective of this study was to examine the suitability of optically stimulated luminescent dosimeters (OSLD) for point dosimetry of maxillofacial radiographic examinations. STUDY DESIGN: The dose response of OSLD nanoDot dosimeters was evaluated over the range of 10 MUGy to 4900 MUGy x radiation. The angular dependence of the OSLD nanoDots was examined and compared with that of thermoluminescent dosimeter (TLD) chips. The concordance between OSDL- and TLD-measured absorbed doses at selected anatomic sites in an anthropomorphometric phantom was examined. RESULTS: OSLD-measured doses were not significantly different from the actual delivered dose, as determined by an ionization chamber. The dose response is linear over the dose response over the examined dose range. Angular variation of OSLD dosimeters ranged from 88% to 109%; however, the magnitude of this variation was not significantly different from that of TLDs. There was a good concordance between OSLD- and TLD-measured absorbed doses. CONCLUSIONS: The OSLD nanoDots dosimeter system performs as well as currently used TLD systems and effective dose estimates using this new system did not differ significantly from current TLD-based dose estimates. PMID- 21983292 TI - Validity and reliability of patient-centered outcome measures in oral dysesthesia. AB - OBJECTIVE: The objective of this study was to investigate the validity and reliability of a quality of life instrument in patients with oral dysesthesia. STUDY DESIGN: Forty-five individuals newly diagnosed with oral dysesthesia (37 women, 8 men) were enrolled in this study. Individuals were interviewed using the Visual Analogue Scale (VAS), and the Oral Health Impact Profile (OHIP-14). Construct validity and internal reliability were examined. RESULTS: Patient rating of pain experienced, using VAS, correlated with OHIP-14 scores (P < .05), demonstrating construct validity. OHIP-14 demonstrated good internal consistency with Cronbach's alpha of 0.79. The corrected item-total correlations for items 3 (painful aching) and 12 (difficulty doing usual jobs) were below the recommended minimum of 0.20. Cronbach's alpha increased to 0.81 with the exclusion of these 2 items from OHIP-14. CONCLUSIONS: The OHIP-14 questionnaire appeared to perform relatively well in the 45 patients with oral dysesthesia enrolled in this study, demonstrating validity and reliability in the assessment of the effect of oral dysesthesia on quality of life. However, the exclusion of items 3 and 12 from the questionnaire should be considered in future studies with this patient population. PMID- 21983294 TI - Cannabis use stages as predictors of subsequent initiation with other illicit drugs among French adolescents: use of a multi-state model. AB - The aim of this study was to confirm the influence of cannabis use patterns on the probability of initiation with other illicit drugs (OID). A French nationwide retrospective cohort on drug use was reconstituted on 29,393 teenagers. A Markov multi-state model was fitted, modelling all possible pathways from initial abstinence to cannabis initiation, daily cannabis use and OID initiation. The model was adjusted for tobacco and alcohol use. The risk for OID initiation appeared 21 times higher among cannabis experimenters and 124 times higher among daily cannabis users than among non-users. Tobacco and alcohol use were associated with a greater risk of moving on to cannabis initiation (hazard ratio (HR)=1.2 for tobacco initiation, HR=2.6 for daily tobacco use and HR=2.8 for drunkenness initiation). The results of this study provide a confirmation of a stage process in drug use, mediated by cannabis and liable to lead to OID experiment. This is compatible with the literature on the gateway theory, but goes further by modelling the entire sequence of use. OID experiment could be a consequence of initial opportunity to use the more accessible illicit drug, cannabis. PMID- 21983295 TI - Both olfactory epithelial and vomeronasal inputs are essential for activation of the medial amygdala and preoptic neurons of male rats. AB - Chemosensory inputs signaling volatile and nonvolatile molecules play a pivotal role in sexual and social behavior in rodents. We have demonstrated that olfactory preference in male rats, that is, attraction to receptive female odors, is regulated by the medial amygdala (MeA), the cortical amygdala (CoA), and the preoptic area (POA). In this paper, we investigated the involvement of two chemosensory organs, the olfactory epithelium (OE) and the vomeronasal organ (VNO), in olfactory preference and copulatory behavior in male rats. We found that olfactory preferences were impaired by zinc sulfate lesion of the OE but not surgical removal of the VNO. Copulatory behaviors, especially intromission frequency and ejaculation, were also suppressed by zinc sulfate treatment. Neuronal activation in the accessory olfactory bulb (AOB), the MeA, the CoA, and the POA was analyzed after stimulation by airborne odors or soiled bedding of estrous females using cFos immunohistochemistry. Although the OE and VNO belong to different neural systems, the main and accessory olfactory systems, respectively, both OE lesion and VNO removal almost equally suppressed the number of cFos-immunoreactive cells in those areas that regulate olfactory preference. These results suggest that signals received by the OE and VNO interact and converge in the early stage of olfactory processing, in the AOB and its targets, although they have distinct roles in the regulation of social behaviors. PMID- 21983296 TI - Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert butyl-4-[(3-nitrophenoxy) methyl]-2,2-dimethyloxazolidine-3-carboxylate. AB - AIMS: We evaluated biological activity in leukemia cells lines of R and S enantiomers of tert-butyl 4-[(3-nitrophenoxy)-methyl]-2,2-dimethyloxazolidine-3 carboxylate (BNDC). MAIN METHODS: Cytotoxic activity was assessed by MTT assay. Flow cytometry assays were used to determined DNA fragmentation (Propidium Iodide PI staining) and phosphatidylserine exposure (Annexin-V and PI staining). DNA condensation was evaluated by fluorescence microscopy using double-staining in leukemia cells (Hoechst and PI). Caspase activities were measured using Z-VAD FMK, a non-selective caspase inhibitor, by flow cytometry and Z-DEVD-AMC, a selective caspase-3 substrate, by fluorescence spectrometry. KEY FINDINGS: Both enantiomers displayed cytotoxic activity against leukemia cell lines (HL60, HL60.Bcl-2, HL60.Bcl-XL and Jurkat) with low toxicity against human peripheral blood mononuclear cell--PBMC based on IC50 values. In HL60 cell lines, compounds induce exposure of phosphatidylserine and DNA fragmentation, which could be blocked by pretreatment of cells with Z-VAD-FMK. Confirming this observation, both enantiomers induced caspase-3 activation. Additional analysis revealed an increased percentage of apoptotic cells (defined as those with fragmented nuclei and condensed chromatin) after treatment with compounds. SIGNIFICANCE: Taken together, the results indicate that BNDC compounds exhibited cytotoxic and pro apoptotic activities and have a potential for developing a new class of anticancer drugs. PMID- 21983297 TI - Altered intestinal P-glycoprotein expression levels in a monosodium glutamate induced obese mouse model. AB - AIMS: P-glycoprotein (P-gp) is an important drug efflux transporter located in many tissues such as the blood-brain barrier, intestines, liver and kidneys. We have previously reported that ileal P-gp expression levels decrease via a nitric oxide synthase (NOS)-mediated pathway in a streptozotocin (STZ)-induced type 1 diabetic mouse model. Herein, our objective was to assess whether there are differences in the expression of intestinal P-gp in an obesity-induced hyperglycemic mouse model versus the type 1 diabetic mouse model. MAIN METHODS: The hyperglycemia-accompanied obese mouse model was developed through an injection of monosodium glutamate (MSG). We analyzed intestinal P-gp expression using Western blot analysis. KEY FINDINGS: Body weight, body mass index, blood glucose levels and serum insulin levels increased significantly with age in the MSG-treated mice. Furthermore, in 24week-old MSG-treated mice, while intestinal P gp expression levels were tended to increase P-gp expression in the duodenum, it was only significant in the jejunum, but not in the ileum. Additionally, the hyperglycemia-accompanied increase in intestinal NOS activity of STZ-treated mice was not evident in the MSG-treated mice. SIGNIFICANCE: Our results suggest that P gp expression levels in the upper part of the intestine increase with age in a hyperglycemia/hyperinsulinemia (i.e. type 2 diabetes) -associated MSG-treated obese mouse model, and that these results completely differ from those found in the STZ-induced type 1 diabetic mouse model. PMID- 21983298 TI - A pilot study on the association between double positive Chlamydia pneumoniae serology and serum lipid indices alterations in obese adult females. AB - AIMS: To study the relationship between Chlamydia pneumoniae serologic status and serum lipid abnormalities in apparently healthy obese female subjects living in urban areas. MAIN METHODS: Serum samples from 117 apparently healthy females (mean age 50 years), classified as overweight/obese (OW/OB,n=74) or normal weight (NW,n=43) according to their body mass index (BMI), were tested for specific IgG and IgA antibodies against C. pneumoniae using ELISA assay. Serum triglycerides (TG), total cholesterol (TChol) and high-density lipoprotein cholesterol (HDLChol) concentrations were measured using enzymatic methods. Serum low-density lipoprotein cholesterol (LDLChol) was calculated using the Friedewald formula. Lifestyle data for all subjects were collected using a validated self-reported questionnaire. KEY FINDINGS: The prevalence of C. pneumoniae infection, as indicated by single positive serology (IgG(+) or IgA(+)), was significantly higher among the OW/OB females than the NW subjects (38.5%vs.27.0%,p=0.021). Females with double-positive serology (IgG(+)/IgA(+)) in the OW/OB group indicated significantly higher (p<0.05) mean serum TG, TChol and LDLChol levels compared to the double seronegatives (IgG(-)/IgA(-)) from this group. On the contrary, no statistical differences (p>0.05) were observed in these serum lipid indices between subjects in the NW group with considered opposite C. pneumoniae serology. Multivariate regression analysis on the 42 double-seropositive subjects, including both OW/OB and NW females and adjusted for such potential confounders as age, BMI and lifestyle factors, showed a significant association of double-positive C. pneumoniae serology with serum TG (beta=0.244;p=0.049),LDLChol (beta=0.332;p=0.037) and TChol-to-HDLChol ratio (beta=0.313;p=0.042). SIGNIFICANCE: These results suggest that possible chronic C. pneumoniae infection is a potential non-dietary factor in modification of the serum lipid profile in the adult OW/OB females. PMID- 21983299 TI - mGlu5 receptor deletion reduces relapse to food-seeking and prevents the anti relapse effects of mGlu5 receptor blockade in mice. AB - AIMS: Convergent data suggest that there is a hyperglutamatergic state that arises during relapse to drug seeking. Blockade of mGlu5 receptors provides one approach to dampening glutamate tone. However, the role of mGlu5 receptors in relapse to food seeking behavior has not been explored extensively and has not been scrutinized using receptor null mice. MAIN METHODS: Wild-type (WT) and mGlu5 receptor knockout (KO) mice were compared under the acquisition of a discriminated operant response maintained by food, during extinction of the response, and during the reinstatement of the response by food and food associated stimuli. The impact of the mGlu5 receptor antagonist MTEP was investigated. KEY FINDINGS: Acquisition and extinction were not markedly different in WT and KO mice. MTEP decreased response reinstatement in WT mice. This behavioral effect of MTEP was not present in the KO mice, demonstrating the dependence of the effect of MTEP on mGlu5 receptors. As with the effect of MTEP in WT mice, receptor deletion reduced response reinstatement in KO mice. SIGNIFICANCE: This is the first report to evaluate the reinstatement of food seeking in mGlu5 receptor KO mice. The data reported here add to those in the literature that support a role for mGlu5 receptors in the control of this relapse effect. The data also reinforce the potential utility of mGlu5 receptor antagonists in relapse prevention to food-seeking behaviors. PMID- 21983300 TI - 16-hydroxycleroda-3,13-dien-15,16-olide regulates the expression of histone modifying enzymes PRC2 complex and induces apoptosis in CML K562 cells. AB - AIMS: Histone modifications play central epigenetic roles in regulating the entire genome of the cell and cell proliferation. Herein, we investigated the effects of the natural compound, 16-hydroxycleroda-3,13-dien-15,16-olide (PL3), on the expressions of histone-modifying enzymes, and examined how it induces apoptosis in leukemia K562 cells. MAIN METHODS: Cell proliferation was determined by an MTT assay, and histone-modifying enzyme gene expressions were investigated by a quantitative real-time PCR. Protein expressions were analyzed by a Western blot analysis. The histone H3K27 distribution was observed with immunofluorescence staining. To verify polycomb repressive complex 2 (PRC2) complex downstream gene expressions, a gene-expression array was performed to determine gene regulations. KEY FINDINGS: PL3 induced apoptosis and modulated many histone-modifying enzymes, especially the two PRC2 components, enhancer of zeste homolog 2 (EZH2) and suppressor of zeste 12 homolog (Suz12). Genes repressed by PRC2 were shown to be reactivated by PL3. Of these, 10 genes targeted by the PRC2 complex were identified, and expressions of 10 pro /antiapoptotic genes were significantly regulated; these effects may have contributed to PL3-induced apoptosis in K562 cells. Regulation of other histone modifying enzymes, including Aurora B, may also be involved in cell-cycle regulation. SIGNIFICANCE: Our data suggest that the induction of apoptosis by PL3 might partly occur through both a reduction in PRC2-mediated gene silencing and the reactivation of downstream tumor suppressor gene expressions. PL3 acts as a novel small-molecule histone modulator, which can potentially contribute to cancer chemotherapy singly or as a combined medication. PMID- 21983301 TI - Effect of povidone-iodine concentration and exposure time on bacteria isolated from endophthalmitis cases. AB - PURPOSE: To determine the in vitro susceptibility of post-cataract surgery endophthalmitis bacterial isolates to different concentrations of povidone-iodine at different exposure times. SETTING: Poostchi Ophthalmology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. DESIGN: Experimental study. METHODS: Ocular-fluid samples obtained from patients diagnosed with postoperative endophthalmitis were submitted to a microbiology laboratory for culture. One milliliter of microbial isolate suspension with a McFarland standard turbidity of 0.5 was mixed with 1 mL of 1%, 2%, 5%, and 10% povidone-iodine solutions. After 1 minute, 5 minutes, and 15 minutes of exposure at 37 degrees C, each solution was transferred to appropriate culture media and incubated at 37 degrees C for 24 hours. RESULTS: Organisms were isolated in 30 (68%) of the 44 patients evaluated. Coagulase-negative Staphylococcus was identified in 14 cases (47%), Streptococcus species in 8 cases (27%), Staphylococcus aureus in 5 cases (17%), Bacillus cereus in 2 cases (6%), and Pseudomonas aeruginosa in 1 case (3%). Higher povidone iodine concentrations and longer exposure times were more effective than lower povidone-iodine concentrations or shorter exposure in preventing growth of bacterial isolates. The most effective regimens were 5% povidone-iodine for 15 minutes and 10% povidone-iodine for at least 5 minutes. With a high bacterial load, 13% of bacterial isolates remain viable after exposure to 10% povidone iodine, even with a long exposure time. CONCLUSION: Results indicate that using 5% povidone-iodine for 15 minutes or 10% povidone-iodine for 5 minutes can prevent the growth of most post-cataract surgery endophthalmitis bacterial isolates. PMID- 21983302 TI - Does the clinical setting matter when performing PCI in a patient on oral anticoagulation? PMID- 21983303 TI - Update on transcatheter aortic valve implantation registries and studies. AB - For patients at increased surgical risk and those not suitable candidates for surgical aortic valve replacement, transcatheter aortic valve implantation has emerged as a promising less-invasive treatment option, with a growing body of evidence on safety and efficacy in this particular patient population. However, the enthusiasm we have been witnessing over the past decade is almost exclusively supported by registry data, with the first randomized trial published only recently. In this paper, we provide an overview on the current data set available on transcatheter aortic valve implantation using the commercially available devices, focusing on the latest publications reflecting the current opinion on this emerging technology. PMID- 21983304 TI - Review of clinical data with Paccocath- coated balloon catheters. AB - The use of drug-coated balloons (DCB) for preventing restenosis in both coronary and peripheral arteries has received increasing attention. The first successful clinical outcomes in inhibiting restenosis have been reported for paclitaxel coated balloons. Paclitaxel is a lipophilic substance characterized by rapid intracellular uptake and irreversible binding to microtubules. In this way, paclitaxel alters the cell structure, ultimately reducing proliferation, migration, and signaling. These properties make paclitaxel a very potent antiproliferative drug. Paclitaxel admixed to a small amount of the hydrophilic X ray contrast medium iopromide (UltravistTM) emerged as a very effective coating matrix from numerous in vitro and in vivo experiments and has been denoted as PaccocathTM. The randomized controlled ISR I/II-, Thunder- and FEMPAC studies have been conducted using PaccocathTM balloons. Late lumen loss as the primary endpoint at 6 months proved to be statistically significantly reduced in the coated balloon groups in coronary and peripheral arteries. The slightly modified coating on the SeQuentTM Please balloons (B.Braun, Melsungen, Germany) has been clinically studied in the PEPCAD (Paclitaxel-Eluting PTCA-Catheter in Coronary Artery Disease) clinical trial program. CotavanceTM balloons (MEDRAD Inc, Minneapolis, USA) are also coated with the PaccocathTM formulation. In this review we first outline the development of PaccocathTM balloons to then provide an overview of the clinical results obtained with the modified coating. Furthermore we examine possible mechanism of action by which single administration of an antiproliferative drug dose using paclitaxel-coated balloons inhibits restenosis. PMID- 21983305 TI - Titanium-nitride-oxide-coated Titan-2 bioactive coronary stent: a new breakthrough in interventional cardiology. AB - The introduction of drug-eluting stents (DES) has revolutionized the field of interventional cardiology, since it has reduced the incidence of restenosis by 50% to 70%. However, recent worrisome data from registries and meta-analyses emphasized higher rates of late and very late stent thrombosis associated with DES. The recently introduced titanium-nitride-oxide-coated stent bioactive stent (Titan-2) was manufactured by a proprietary process to coat titanium-nitride oxide on the surface of the stainless steel stent, based on a plasma technology using the nano-synthesis of gas and metal. This late-breaking stent has demonstrated an excellent biocompatibility, as reflected by lower rates of platelet aggregation and fibrin deposition, and better endothelialization. Preclinical and clinical trials and registries involving real-life unselected populations have shown a low rate of major adverse cardiac events at long-term follow-up. Restenosis rates were comparable with those of DES, with very rare stent thrombosis. Equally favorable results have been obtained in patients at high-risk of in-stent restenosis, such as diabetics and those with small coronary arteries. Results in patients presenting with acute coronary syndrome have been again comparable to those of DES, with tendency to lower rates of myocardial infarction and stent thrombosis. Comparisons with second generation drug-eluting stents have also been promising. PMID- 21983306 TI - Patient selection for MitraClip therapy impaired left ventricular systolic function. AB - Mitral regurgitation (MR) is a disabling disease associated with poor prognosis and high incidence of clinical events if left untreated. To reduce the invasiveness of the surgical approach, different types of transcatheter procedures are becoming available. The MitraClip procedure (Abbott Vascular Inc. Menlo Park, CA, USA) is yet the only catheter-based procedure available in clinical practice at the moment. The device has been evaluated in a number of preclinical studies, registries and in FDA approved clinical trials. (EVEREST trial, ACCESS-EU trial). Indication and timing of intervention is a crucial step in the diagnostic-therapeutic pathway of patients with mitral regurgitation. The aim of this review is to clarify the potential of MitraClip in clinical practice, particularly focusing on patient selection for this novel therapy. Patient selection and overall decision making is strongly influenced by anatomical and clinical factors. Decision-making in degenerative MR (DMR) vs. functional (FMR) can be quite different. Generally, MitraClip is effective in treating either type II or IIIb dysfunction (at the moment FMR is the main indication for MitraClip in Europe, according to the ACCESS registry data). The relative role of MitraClip and surgery in the management of patients with MR is still unclear. From the global initial experience, MitraClip therapy could be complementary to surgery in those patients at high risk for surgery who have ideal anatomical characteristics for implantation. The procedure is quite predictable in patients with favorable anatomy. In patients with suboptimal anatomy, if the risk of surgery is too high, MitraClip could be still indicated sometimes. Our preliminary experience suggests that in patients with DMR, the EVEREST anatomical criteria are strong predictors of early and mid-term success. According to it, MitraClip therapy is appropriate in those DMR patients with high surgical risk and ideal anatomy for clip implantation according to the EVEREST criteria. In FMR refractory to medical therapy and resynchronization therapy, MitraClip could be considered as first option therapy, particularly in those patients with comorbidities, or advanced age, being the operative risk of surgery above 5% in this population. In the future, novel devices, improved knowledge, more efficient imaging and transcatheter mitral prosthetic valve implantation may expand the indications to those patients currently not treated by MitraClip for anatomical unsuitability, and may improve the results both in term of early efficacy and long term durability. PMID- 21983307 TI - Contrast echo: really safe after all? AB - Echocardiography has been integrated into clinical practice as an indispensable tool providing adjunctive diagnostic and prognostic information, crucial for optimal patient management. In addition, contrast echocardiography is regarded as a major technological breakthrough in the field of cardiovascular imaging as it provides not only images of superior quality, but also extents the clinical application of echocardiography in a variety of clinical scenarios including the assessment of coronary artery disease, cardiomyopathies and structural heart disease. However, several experimental studies and data deriving from post-market observations have put contrast agents to the test due to raised concerns regarding their safety profile. Specifically, animal studies have demonstrated detrimental bioeffects, presumably attributed to a phenomenon called inertial cavitation, which lead to endothelial dysfunction of various organs including the heart. Therefore, the European Medicines Agency (EMEA) and the Food and Drug Administration (FDA), in 2004 and 2007 respectively, issued warnings, according to which contrast implementation in echocardiography was considered hazardous, as it was connected to fatalities occurring several minutes after intravenous infusion. On the other hand, multiple large clinical trials have contradicted contrast incrimination, by illustrating an excellent safety profile of contrast agent utilization in a variety of clinical settings such as hospitalized patient in the Intensive Care Unit and stress echocardiography, condition that could render patients prone to ischemic and arrhythmic events. Moreover, the documented clinical efficacy of contrast agents has led both the EMEA and the FDA to reconsider their initial statements and reinstate contrast deployment during echocardiographic examinations. As a result, the American Society of Echocardiography published in 2008 a consensus statement, according to which an extended list of applications was recommended. PMID- 21983308 TI - Contrast echo and perfusion stress (2D/3D): which role in clinical practice? AB - In this review we will clarify some key technical aspects of myocardial contrast echocardiography (MCE) but we will mostly address its potential clinical application during stress-echocardiography in today's cardiology practice, according to the literature and to the author's view. MCE is a bedside technique, it is cheap and has a very high diagnostic accuracy and safety. Nonetheless MCE use remains confined to the few echolabs which pioneered and developed the technique: Why is that? We here suggest a number of potential explanations for this research/clinical practice "mismatch", and how to overcome it, putting MCE in its proper cardinal role among diagnostic methods in cardiology. PMID- 21983309 TI - Contrast echocardiography: finding its place in stem cell therapy. AB - To date, the underlying mechanism responsible for the restoration of the injured myocardium following transplantation of stem cells has not been clearly identified. Molecular imaging is essential to the continued progress of stem cell therapy by elucidating the biology of transplanted stem cells in vivo. Currently, several imaging modalities are in development in the rapidly evolving field of molecular imaging. Contrast echocardiography has the potential to define its role in shaping the future development of stem cell therapy. We describe the current state of contrast echocardiography and its future direction herein. PMID- 21983310 TI - Coronary stenting for ST-elevation myocardial infarction vs. other indications in patients on oral anticoagulation: any difference in in-hospital management and outcome? AB - AIM: The aim of this paper was to compare the in-hospital management and outcome of patients on oral anticoagulation (OAC) undergoing coronary artery stenting (PCI-S) for ST-elevation myocardial infarction (STEMI) vs. other indications. METHODS: One hundred and sixteen patients on OAC at the time of PCI-S who were prospectively enrolled in a multi-center, observational registry, were evaluated. Patients were segregated according to whether PCI-S was performed for STEMI (group 1) or other indications, such as non ST-elevation acute coronary syndromes, stable angina, silent ischemia, etc. (group 2), and the pharmacological and procedural management, as well as the in-hospital outcome, were compared. RESULTS: No significant differences were observed in vascular access site, sheath size and type of stent implanted, nor was significantly different the use of glycoprotein IIb/IIIa inhibitors, and the use and dose of intravenous unfractionated heparin. Although not statistically different, the in hospital occurrence of death (3.7% vs. 1.1%; OR 3.3; 95% confidence intervals [CI] 0.2-56.0), stent thrombosis (3.7% vs. 1.1%; OR 3.3; 95% CI 0.2-56.0) and major bleeding (7.4% vs. 2.2%; OR 3.4; 95% CI 0.4-25.9) was consistently about 3 fold higher in group 1. CONCLUSION: The in-hospital pharmacological and procedural management of OAC patients undergoing PCI-S for STEMI vs. other indications appears not different. Although not significantly different however, the in-hospital occurrence of major bleeding, as well as of death and stent thrombosis, appears substantially higher in patients treated for STEMI, warranting therefore further larger, prospective studies. PMID- 21983311 TI - Percutaneous mitral valve treatment. AB - Over the last decade a multitude of transcatheter technologies, many of them based on surgical mitral repair techniques, are being developed. This manuscript describes some of these technologies based on their mechanism of action. PMID- 21983312 TI - Current applications of contrast echocardiography. AB - Transthoracic echocardiography is a practical, widely available non-invasive imaging technique examining cardiac structure and function at rest and during stress. However, diagnostically useful images are not provided in a non negligible proportion of patients, mainly because of obesity and lung disease. The use of echo-contrast agents (microbubbles consisting of high molecular weight gas encapsulated in a outer shell which have ultrasound characteristics distinctly different from those of the surrounding blood cells and heart tissue) solves these issues, providing cardiac chamber opacification and improving endocardial border definition, consequently allowing a more accurate quantification of left ventricular function. Besides improving the assessment of left ventricular function, echo-contrast agents may be used also to assess the myocardial perfusion at the capillary level, providing useful information about myocardial blood flow. Aim of the present paper is to provide an overview of the main clinical applications of contrast echocardiography, i.e. left ventricular opacification and myocardial contrast echocardiography. PMID- 21983313 TI - Allopurinol as a cardiovascular drug. AB - Cardiovascular disease (CVD) remains the leading cause of death in the United States. There is evidence that shows a direct relationship between an elevated uric acid level and an increased risk of cardiovascular (CV) events, which has set the foundation for the investigation of uric acid-lowering drugs for the treatment of CVD. Although traditionally the cornerstone therapy for gout, allopurinol's ability to be a competitive inhibitor of the key enzyme, xanthine oxidase, needed for uric acid formation, has prompted recent clinical research evaluating allopurinol as a CV drug. Epidemiologic and biochemical studies on uric acid formation have shown that it is not only uric acid itself that leads to worsening prognosis and increased CV events, but also the free radicals and superoxides formed during xanthine oxidase activity. The combination of uric acid formation and formed free radicals could ultimately lead to coronary endothelial dysfunction and worsening of myocardial oxidative stress. Along with preventing uric acid formation, allopurinol also has the ability to behave as a free radical scavenger of the superoxide anions and free radicals released during uric acid formation.Clinical studies have shown that allopurinol improves endothelial dysfunction and subsequently improves the exercise capacity in patients diagnosed with angina pectoris. Allopurinol has also been shown to decrease oxidative stress and ameliorate the morbidity and mortality of congestive heart failure patients by possibly improving mechanoenergetic uncoupling, with the enhancement of myocardial contractility and the left ventricular ejection fraction. This review presents the pharmacologic action of allopurinol on the CV system and describes the effectiveness of allopurinol as a potential drug to treat 2 CVD morbidities: ischemic heart disease and congestive heart failure. PMID- 21983314 TI - Bromocriptine for diabetes mellitus type II. AB - A quick-release formulation of bromocriptine is the latest drug approved by the US Food and Drug Administration for the treatment of type 2 diabetes mellitus. Most interestingly, the development of this drug stems from studies of hibernation in rodents. This article will review the physiology that led to the development of this new drug, as well as its indications, clinical use, benefits, and contraindications. PMID- 21983315 TI - Acetazolamide: a forgotten diuretic agent. AB - Acetazolamide is the only carbonic anhydrase inhibitor with significant diuretic effects. It is readily absorbed and undergoes renal elimination by tubular secretion. Its administration is ordinarily marked by a brisk alkaline diuresis. Although carbonic anhydrase inhibitors are proximal tubular diuretics (where the bulk of sodium re-absorption occurs), their net diuretic effect is modest in that sodium re-absorption in more distal nephron segments offsets proximal sodium losses. Acetazolamide use is limited by both its transient action and the development of metabolic acidosis with extended administration. Acetazolamide can, however, correct the significant metabolic alkalosis which occasionally occurs with loop diuretic therapy. PMID- 21983316 TI - Obstructive sleep apnea and cardiovascular disease. AB - Obstructive sleep apnea (OSA) is a sleep-disordered breathing condition, which is increasingly being recognized as having wide-ranging pathophysiological effects on multiple organ systems. Although multiple factors affect the incidence and severity of OSA, male sex and obesity seem to play an influential role. The apnea ventilation cycle, characterized by abnormalities in gas exchange, exaggerated respiratory effort and frequent arousals, has been shown to have deleterious effects on circulatory hemodynamics, the autonomic milieu, hormonal balance, inflammatory and coagulation cascades, endothelial function, and the redox state, with potential cardiovascular significance. Consequently, OSA is being increasingly implicated in a multitude of cardiovascular diseases (CVD) such as hypertension, congestive heart failure, atrial fibrillation, stroke, coronary artery disease, pulmonary hypertension, and metabolic syndrome. The strength of association for individual CVD is varied, and outcomes of clinical studies are conflicting. In addition, obesity, which is closely linked to both OSA and CVD, makes it harder to ascertain the independent role of OSA on CVD. Although available evidence is inconclusive, there is an increasing recognition of the direct role for OSA in CVD. Similarly, although several studies have demonstrated the cardiovascular benefits of OSA treatment, further studies are needed to confirm this. PMID- 21983317 TI - Subclinical hypothyroidism and cardiovascular risk: recommendations for treatment. AB - The definition of subclinical hypothyroidism (SCH) is solely biochemical: a serum free T4 level within the reference range in the presence of an elevated serum thyroid-stimulating hormone (TSH) level. While overt hypothyroidism is associated with an increased cardiovascular disease risk, SCH, the mildest form of hypothyroidism, may also be associated with an increased cardiovascular disease risk, but to a lesser degree. Recent evidence points to a significant trend toward an increase in cardiovascular risk at higher TSH levels, with TSH levels >=10 mIU/L associated with increased cardiovascular morbidity and mortality. It is generally recommended to treat with thyroid hormone those individuals with SCH and TSH values >=10 mIU/L. Treatment of patients with SCH and TSH values <10 is controversial but may be considered in selected patients. PMID- 21983318 TI - Azilsartan: a newly approved angiotensin II receptor blocker. AB - Hypertension is a common chronic disease that leads to significant cardiovascular morbidity and mortality. Blood pressure control is essential to prevent end-organ complications, such as stroke, myocardial infarction, heart failure, or kidney disease. Azilsartan is the eighth angiotensin II receptor blocker approved for the management of hypertension, alone or in combination with other agents. At the approved dosage, it reduces systolic blood pressure by 12 to 15 mm Hg and diastolic blood pressure by 7 to 8 mm Hg. A higher dose of azilsartan (80 mg) was superior to valsartan 320 mg or olmesartan 40 mg in lowering systolic blood pressure in short-term studies. Additional blood pressure reduction is expected when azilsartan is used adjunctively with a diuretic. However, the effects of azilsartan on cardiovascular morbidity or mortality are still lacking. Azilsartan is well tolerated; the most common side effects are headache and diarrhea. No cases of hyperkalemia have been reported in 6-week clinical trials. Worsening of renal function and hypotension should be monitored, particularly in those with baseline risk factors. It is unknown whether azilsartan would join angiotensin converting enzyme inhibitors and other angiotensin receptor blockers as the preferred hypertensive agents for end-organ protection. At this time, azilsartan should be considered as an alternative agent for mild-to-moderate hypertension, or as an adjunctive therapy when preferred agents fail to maintain optimal blood pressure control. It is also an option for those patients who have contraindications or cannot tolerate other antihypertensive agents, including dry cough induced by angiotensin-converting enzyme inhibitors. PMID- 21983319 TI - Toxicological assessment of selective pesticides towards plant growth promoting activities of phosphate solubilizing Pseudomonas aeruginosa. AB - The study was designed to assess the effect of selected pesticides (metribuzin, glyphosate, imidacloprid, thiamethoxam, hexaconazole, metalaxyl and kitazin) at the recommended and higher rates on plant growth promoting activities of Pseudomonas aeruginosa strain PS1 isolated from mustard (Brassica compestris) rhizosphere. The strain PS1 was specifically chosen owing to its substantial tolerance against pesticides, phosphate solubilization and considerable production of indole acetic acid, siderophores, exo-polysaccharides, HCN and ammonia. Plant growth promoting traits of the strain PS1 decreased consistently as the concentrations of each pesticide was increased from the recommended dose to the higher ones. Generally, the maximum toxicity to plant growth promoting traits was displayed by pesticides at three times the recommended field rate. However, the effect on the plant growth promoting activities of the P. aeruginosa strain PS1 at the recommended dose of each pesticide was less hazardous. This study revealed an additional aspect of the toxicological mechanisms of the pesticides through which they suppress the plant growth. PMID- 21983320 TI - Production of beta-carotene from deproteinized waste whey filtrate using Mucor azygosporus MTCC 414 in submerged fermentation. AB - The cheese whey, a by-product of dairy industry proved to be an attractive substrate for production of beta-carotene. The beta-carotene production from Mucor azygosporus MTCC 414 by using deproteinized waste whey filtrate under submerged fermentation was investigated. Various fermentation variables, such as lactose content in whey, initial pH, production temperature, incubation time, and carbon and nitrogen sources played significant role on beta-carotene production. Maximum beta-carotene production (385 MUg/g dcw) was obtained with the whey (pH 5.5) containing 3.5% (w/v) lactose supplemented with soluble starch at (1.0%, w/v) at 30 degrees C after a 5 days incubation. Moreover, unlike other microorganisms which utilize pre-hydrolyzed lactose, this Mucor azygosporus MTCC 414 was found to be capable of utilizing unhydrolyzed lactose present in the whey. PMID- 21983321 TI - Interaction of concanavalin a with bacterial lipopolysaccharides in agarose gel. AB - Binding of fluorescein isothiocyanate-labeled concanavalin A to a series of molecular species of lipopolysaccharide (LPS), purified from pathogenic bacteria, was studied via agarose gel precipitation experiments and the results were compared with available structural data.The LPS species could be divided into ConA-reactive and non-reactive ones. Reactivity resided in the O-specific chain of LPS, and binding to the lipid A or core moieties of LPS could not be demonstrated by the present methods. The alpha-D-glucose or alpha-D-mannose residues of the repeating O-specific oligosaccharide units appeared to be recognized by ConA, except when blocked by steric hindrance. Specificity of the reaction was verified by inhibition with 2% D-glucose. Binding by bacterium specific sugar-residues could not be demonstrated.For precipitation to occur, polyvalency was required both for LPS and ConA, and the resulting precipitation appeared to be promoted by hydrophobic interactions between the lipid A moieties of LPS molecules. The LPS species were differently retained by the agarose gel, which can be explained by differences in their micellar structure in aqueous solution. E. coli O83 LPS did not readily diffused in 1% agarose gel, but its precipitation with ConA could be demonstrated either at elevated temperature or mixing it previously with molten agarose (Mancini's arrangement). PMID- 21983322 TI - Cytochrome CYP141: a new target for direct detection of Mycobacterium tuberculosis from clinical specimens. AB - Cytochrome P450 CYP141 is an intermediary metabolic and respiratory protein that interferes with oxidation reduction in Mycobacterium tuberculosis. This conserved protein has also been debated as a hypothetical target for therapeutics. We used the sequences of CYP141 gene to develop a PCR for rapid detection of Mycobacterium tuberculosis from respiratory specimens. The sensitivity of this PCR for culture positive-smear positive and culture positive-smear negative samples were 92% and 62.5%, respectively. The overall sensitivity and specificity of this PCR was 85.7% and 97.8%. As compared with other studies, it appears that the CYP141 gene is a good target for direct detection of M. tuberculosis from respiratory specimens. PMID- 21983323 TI - Time-kill study and synergistic activity of cell-wall inhibitor antibiotics in combination with gentamicin against Enterococcus faecalis and Enterococcus faecium. AB - The synergy between gentamicin and vancomycin, teicoplanin, ampicillin and linezolid was studied by time-kill method. Two clinical vancomycin resistant enterococci (VRE) and two vancomycin susceptible enterococci (VSE) isolates were used. Different concentrations of antibiotics were combined. Two VSE strains and the control strain exhibited synergism with the combination of gentamicin, vancomycin, teicoplanin, ampicillin and linezolid. Two VRE strains exhibited synergism with the combination of gentamicin and ampicillin. Synergy between gentamicin and vancomycin, teicoplanin and linezolid was not observed against these isolates. The VRE isolates were positive for vanA, aac (6')-Ie aph (2") and aph (3')-IIIa genes and their vancomycin, teicoplanin and gentamicin MICs were 512 MUg/ml, 512 MUg/ml and >4000 MUg/ml, respectively. In order to treat serious enterococcal infections, further clinical evaluation is needed to examine the in vitro combined effects of gentamicin and vancomycin, teicoplanin and linezolid. PMID- 21983324 TI - Nasal carriage of methicillin resistant Staphylococcus aureus and their antibiotic susceptibility patterns in children attending day-care centers. AB - Nasal colonization with community acquired methicillin resistant Staphylococcus aureus (CA-MRSA) is being increasingly reported, especially in places where people are in close contact and in reduced hygiene, such as day-care centers. In this study we investigated the frequency of MRSA colonization and their antibiotic susceptibility patterns in 1-6 years old children of day-care centers in Hamadan, West of Iran.Five hundred nasal swabs were collected from children of 27 day-care centers that had no risk factors for colonization by S. aureus. The specimens were cultured for isolation of S. aureus by standard methods. Antimicrobial susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. For evaluation of the frequency of erythromycin induced clindamycin resistance, disk approximation test (D-test) was applied.Totally, 148 (29.6%) children were colonized by S. aureus. Out of 260 male, 94 (36.2%) and of 240 female, 54 (22.5%) cases were nasal carriers of S. aureus (P value = 0.001). Six (4.1%) of the 148 S. aureus isolated from children were MRSA strains. None of MRSA and methicillin susceptible S. aureus (MSSA) was resistant to vancomycin and clindamycin. Three of the 6 strains of MRSA and 7 (4.9%) of the 142 MSSA strains were resistant to erythromycin, and D-test was positive in all of them.We conclude that the rate of colonization by S. aureus is high in children attending day-care centers but colonization with MRSA is not common in our areas. Clindamycin or trimethoprim-sulfamethoxazol could be used in mild to moderataly severe diseases caused by CA-MRSA. However, if the CA-MRSA isolates are erythromycin resistant, D-test should be carried out for detection of inducible clindamycin resistance. PMID- 21983325 TI - Serratia ficaria isolated from sputum specimen. AB - Serratia ficaria was first described in 1979 as a Gram-negative facultative anaerobic rod. S. ficaria was found in figs, but also isolated from human specimens in a few cases. We now report an isolate of S. ficaria from sputum specimen.A 46-year-old man was suffering from a chronic renal failure of five years, four months of peritoneal dialysis and one week of fever due to respiratory tract infection, accompanied by cough. Sputum culture yielded a Gram negative rod. It was identified as S. ficaria and the antibiotic susceptibility test was performed by automated Vitek II (bioMerieux). The tested S. ficaria strain was susceptible to amikacin, gentamicin, cefepime, trimethoprim sulfamethoxazole, imipenem, meropenem, tigecycline and ciprofloxacin. This strain was resistant to ampicillin, amoxicillin-clavulanic acid, cephalothin, cefoxitine, cefuroxime and ceftriaxone. The patient was treated successfully (80 mg trimethoprim/400 mg sulfamethoxazole twice daily for 7 days)S. ficaria is an opportunistic pathogen responsible for intestinal colonization or serious infections such as septicaemia, gall bladder empyema in immunocompromised patients. The fig tree and fig play an important role in human colonization. It should be remembered that S. ficaria infections may be encountered frequently especially in fig tree culture zones. PMID- 21983326 TI - A marked shift in the serotypes of pneumococci isolated from healthy children in Szeged, Hungary, over a 6-year period. AB - Streptococcus pneumoniae is an important pathogen with significant morbidity and mortality rates worldwide, especially among children <5 years. Healthy carriers are the most important sources of pneumococcal infections, and the nasopharyngeal colonisation is the most prevalent among children attending communities such as day-care centres (DCCs). The conjugate pneumococcal vaccines (PCVs) were shown to have an impact on the colonisation, and so play an important role in inhibiting infections. In this study we compared the nasal carriage of healthy children attending DCCs in Szeged, Hungary in 2003/2004, when nobody was vaccinated, and in 2010, when already 1/5 of the children received PCV-7. Significant differences were observed in the serotype distribution, representing a marked shift from the previously widespread vaccine-types (mostly 6A or 14) to others (11A and 23F). The new serotypes showed higher antibiotic susceptibility. The bacterium exchange between children was clear from the pulsed-field gel electrophoresis (PFGE) patterns, and the circulation of certain international clones plays also a role in these dynamic changes. PMID- 21983327 TI - Hydrophobic switching nature of methylcellulose ultra-thin films: thickness and annealing effects. AB - We have studied the thermosensitive property of methylcellulose (MC) thin films supported on Si substrate by static sessile drop contact angle measurements, and their surface properties and thin film structure by x-ray reflectivity (XRR) and atomic force microscopy (AFM) techniques. From the static sessile drop contact angle measurements, the MC thin films showed the characteristic hydrophilic-to hydrophobic transition at ~70 degrees C, which is the lower critical solution temperature of the bulk solution volume phase separation transition. For films with thickness d <= R(g), the onset of such a transition is affected by the film thickness while very thick films, d ? R(g), yielded higher contact angles. Annealing the MC thin films with thicknesses ~200 A (near the radius of gyration, R(g), of the polymer) below the bulk glass transition temperature (T(g) ~ 195 degrees C) would not change the hydrophobic switch nature of the film but annealing 'at' and above the bulk T(g) would change its surface property. From surface topography images by AFM, there were no significant changes in either the roughness or the film texture before and after annealing. With XRR data, we were able to determine that such changes in the surface properties are highly correlated to the film thickness changes after the annealing process. This study, we believe, is the first to examine the thermal annealing affects on the thermal response function of a thermoresponsive polymer and is important for researching how to tailor the hydrophobic switching property of MC thin films for future sensing applications. PMID- 21983328 TI - How to improve exposure of tumor cells to drugs: promoter drugs increase tumor uptake and penetration of effector drugs. AB - Solid tumors are characterized by an abnormal architecture and composition that limit the uptake and distribution of antitumor drugs. Over the last two decades, drugs have been identified that improve the tumor uptake and distribution of drugs that have direct antitumor effects. We propose to refer to these drugs as promoter drugs, and as effector drugs to drugs that have direct antitumor effects. Some promoter drugs have received regulatory approval, while others are in active clinical development. This review gives an overview of promoter drugs, by classifying them according to their mechanism of action: promoter drugs that modulate tumor blood flow, modify the barrier function of tumor vessels, induce tumor cell killing, and overcome stromal barriers. Eventually, we discuss those that we feel are the main conclusions to be drawn from promoter drug research that has been performed so far, and suggest areas of future investigation to improve the efficacy of promoter drugs in cancer therapy. PMID- 21983329 TI - Liposomal drug formulations in cancer therapy: 15 years along the road. AB - Liposomes as pharmaceutical drug carriers were developed to increase antitumour efficacy and decrease drug toxicity. Doxorubicin HCl liposomal injection was the first liposomal encapsulated anticancer drug to receive clinical approval. To date, virtually all traditional anticancer drugs have been encapsulated in liposomes. The majority of clinical studies only support the concept of a decreased toxicity and better tolerability of the liposomal anticancer drug. Although liposomal anticancer drugs have grown to maturity in several indications and are now in widespread further development programmes using their theoretical advantages to fulfil the high expectations, further studies are warranted- including the development of novel liposomal formulations. PMID- 21983330 TI - Homeostatic synaptic plasticity: from single synapses to neural circuits. AB - Homeostatic synaptic plasticity remains an enigmatic form of synaptic plasticity. Increasing interest on the topic has fuelled a surge of recent studies that have identified key molecular players and the signaling pathways involved. However, the new findings also highlight our lack of knowledge concerning some of the basic properties of homeostatic synaptic plasticity. In this review we address how homeostatic mechanisms balance synaptic strengths between the presynaptic and the postsynaptic terminals and across synapses that share the same postsynaptic neuron. PMID- 21983332 TI - Design and synthesis of novel triazole antifungal derivatives by structure-based bioisosterism. AB - The incidence of life-threatening fungal infections is increasing dramatically. In an attempt to develop novel antifungal agents, our previously synthesized phenoxyalkylpiperazine triazole derivatives were used as lead structures for further optimization. By means of structure-based bioisosterism, triazolone was used as a new bioisostere of oxygen atom. This type of bioisosteric replacement can improve the water solubility without loss of hydrogen-bonding interaction with the target enzyme. A series of triazolone-containing triazoles were rationally designed and synthesized. As compared with fluconazole, several compounds showed higher antifungal activity with broader spectrum, suggesting their potential for further evaluations. PMID- 21983331 TI - L-Proline anchored multicomponent synthesis of novel pyrido[2,3-a]carbazoles; investigation of in vitro antimicrobial, antioxidant, cytotoxicity and structure activity relationship studies. AB - The newly synthesized pyrido[2,3-a]carbazoles were prepared in good yields by multicomponent reactions under L-proline as promoter and structurally characterized. Few compounds showed significant activity toward both gram positive, gram-negative bacterial strains. All compounds exerted negative efficacy for antifungal activity except compounds 5f and 7f which showed moderate activity. All compounds showed weak to moderate capacity for scavenging DPPH. The cytotoxicity was evaluated by Sulforhodamine B assay against A-549, B16F10, HCT 15, SKMel2 and SKOV3 cell lines and compared with standard drug cisplatin. Compound 5f outperformed cisplatin against A-549, HCT-15, SKMel2 and B16F10 cell lines. Compound 5e outranged cisplatin against A-549, HCT-15, and SKMel2 cell lines. 5b outperformed cisplatin specifically against B16F10. The preliminary structure activity relationships were carried out. PMID- 21983334 TI - Biomarkers of Parkinson's disease and Dementia with Lewy bodies. AB - Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) are progressive and disabling neurodegenerative disorders, in which signs and symptoms overlap with each other and with other neurodegenerative conditions. Currently, diagnosis, measurement of progression, and response to therapeutic intervention rely upon clinical observation. However, there remains a critical need for validated biomarkers in each of these areas. A definitive diagnostic test would improve clinical management and enrollment into clinical trials. An objective measure of progression is vitally important in identifying neuroprotective interventions. Biomarkers may also provide insight into pathogenesis, and might therefore suggest possible novel targets for therapeutic intervention. In addition, certain biomarkers might be of use in monitoring the biochemical and physiological effects of therapeutic interventions. Development of diagnostic biomarkers has focused until recently upon imaging techniques based upon measuring loss of dopamine neurons. Additionally, advances in understanding the genetic contribution to neurodegenerative disorders, in particular in PD, have identified multiple causative genes and risk factors that in some cases may help estimate PD risk. However, recent availability of increasingly sophisticated bioinformatics technology has rendered development of fluid biomarkers feasible, opening the possibility of generally accessible blood or cerebrospinal fluid (CSF) tests that could impact upon diagnosis, management, and research in PD, PDD, and DLB. PMID- 21983333 TI - A class of novel N-(1-methyl-beta-carboline-3-carbonyl)-N'-(aminoacid-acyl) hydrazines: aromatization leaded design, synthesis, in vitro anti-platelet aggregation/in vivo anti-thrombotic evaluation and 3D QSAR analysis. AB - High anti-thrombotic activity of aminoacid modified tetrahydro-beta-carbolines was generally correlated with a small proximity of the side chain of the aminoacid residue to the carboline-cycle. This paper explored that the aromatization of the tetrahydro-beta-carboline-cycle of N-(1-methyl-beta tetrahydrocarboline-3-carbonyl)-N'-(aminoacid-acyl)-hydrazines leaded to N-(1 methyl-beta-carboline-3-carbonyl)-N'-(aminoacid-acyl)-hydrazines and decreased the proximity of the side chain of the aminoacid residue to the carboline-cycle. The in vitro activities of inhibiting pig platelet aggregation induced by PAF, ADP, and AA, as well as the in vivo anti-thrombotic activities of inhibiting rat thrombosis of these aromatized derivatives were generally higher than that of N (1-methyl-beta-tetrahydrocarboline-3-carbonyl)-N'-(aminoacid-acyl)-hydrazines. The understanding was also obtained from the 3D QSAR analysis. PMID- 21983335 TI - Identification and mRNA expression of pi-class glutathione S-transferase and selenium-dependent glutathione peroxidase in the gudgeon Gobio gobio exposed to PCB 77. AB - In aquatic environments some pollutants are present in water and sediments and organisms possess cellular detoxification systems to face up these xenobiotics. The gudgeon, Gobio gobio, is a freshwater benthopelagic fish that appears particularly adequate for an ecotoxicological assessment of rivers. The aim of this study was the identification of GST and GPx genes in this organism in order to develop new indicators of early exposure to xenobiotics in aquatic environments. Reverse-transcription PCR using degenerate primers and RACE-PCR allowed us to identify a selenium-dependent glutathione peroxidase (Se-GPx), belonging to the class one (GPx-1), and a pi-class glutathione S-transferase (pi GST) cDNAs. These sequences encoded for 191 and 208 amino acids proteins respectively, they exhibit high identities and similarities with corresponding proteins in other fish and the residues essential to the enzymatic functions are highly conserved. The expression patterns of these two mRNA were established by real-time PCR in five gudgeon tissues: liver, gills, kidney, spleen and muscle. The mRNA levels of these genes were highest in the liver and their expression in the other tissues exhibited some differences. Gudgeons exposed to PCB 77 in the food exhibited an increase in pi-GST mRNA and a decrease in GPx-1 transcripts levels in the liver. However, no modification of the enzymatic activities was observed. The present study provides the first transcriptional data regarding pi GST and GPx-1 in the gudgeon Gobio gobio. PMID- 21983336 TI - 8-Oxoguanine DNA glycosylase 1 (OGG1) from the copepod Tigriopus japonicus: molecular characterization and its expression in response to UV-B and heavy metals. AB - 8-Oxoguanine DNA glycosylase 1 (EC 3.2.2.23) is encoded by OGG1 gene and plays a key role in removing 8-oxo-7,8-dihydroguanine (8-oxoG) base in DNA lesion by reactive oxygen species (ROS). To identify and characterize OGG1 gene (TJ-OGG1) in the copepod Tigriopus japonicus, the full-length cDNA sequence, genomic structure, and promoter region was analyzed. In addition, to investigate transcriptional change of TJ-OGG1 mRNA under oxidative stress conditions, T. japonicus were exposed to environmental oxidative inducers, H(2)O(2), UV-B, and heavy metals (Cd, Cu, and Zn), respectively. The full-length cDNA of TJ-OGG1 gene was 1708 bp in length, encoding 343 amino acid residues. The deduced amino acid sequences of TJ-OGG1 showed a 56% similarity with human. Two conserved motifs (HhH and PVD loop) and two conserved residues (lysine and aspartic acid) in active sites were also observed. TJ-OGG1 genome structure contained six exons and five introns and putative transcription factor binding sites such as Nrf-2, p53, ERE-half sites, and XRE were detected on the promoter region. TJ-OGG1 mRNA level was increased at approximately three-fold (P<0.05) at 1mM and approximately 4 fold (P<0.01) at 10mM of H(2)O(2), respectively. UV-B enhanced the expression of TJ-OGG1 mRNA at 15kJ/m(2) (P<0.05) and more (P<0.001). In a time-course experiment, TJ-OGG1 gene was highly transcribed within 12h after exposure of 10 kJ/m(2) (P<0.01) and 20 kJ/m(2) (P<0.001). The expression of TJ-OGG1 mRNA after exposure to Cu and Cd for 96 h was significantly up-regulated at 0.1 MUg/L and then remarkably reduced in a dose-dependent manner. Their transcript levels did not change at low dose (0.1 and 1 MUg/L) but were dose-dependently down-regulated at high dose (10 and 100 MUg/L). These findings suggest that H(2)O(2), UV-B, and heavy metals induce oxidative stress and generate oxidatively damaged DNA. Consequently, the enhanced TJ-OGG1 gene expression would be associated with active involvement of TJ-OGG1 gene in DNA repair process as a cellular protection mechanism. This is the first report on the cloning and characterization of OGG1 gene in aquatic animals. This study is helpful for a better understanding of the molecular mechanisms of cellular protection against various environmental oxidative stress inducers such as UV-B and heavy metals in aquatic invertebrates. PMID- 21983337 TI - From types to trees: reconstructing the spatial spread of Staphylococcus aureus based on DNA variation. AB - Tracing the spatial spread of pathogens is a key objective of molecular infectious disease epidemiology. Accordingly, a wide range of genotyping approaches have been used to monitor the dissemination of Staphylococcus aureus strains, from localized outbreaks to global spread. We provide a critical review of available methods, revealing that molecular markers currently in use for typing S. aureus acquire changes so slowly that they monitor evolutionary change over timescales that are largely irrelevant to epidemiology. Moreover, the more variable markers frequently do not reflect the pathogen's evolutionary history and, hence, provide potentially misleading information about spread. More recent work has demonstrated that staphylococcal evolution proceeds sufficiently fast that the dynamics of S. aureus spatial spread can be elucidated at great detail on the basis of genome-wide single-nucleotide polymorphisms. PMID- 21983338 TI - Livestock-associated methicillin-resistant Staphylococcus aureus in animals and humans. AB - Since 2004 MRSA emerged in animals, particularly in pigs and veal calves. This new MRSA variant was since its first appearance referred to as Livestock Associated-MRSA (LA-MRSA). In Europe and Northern America, LA-MRSA belongs predominantly to clonal complex (CC) 398 whereas in Asia ST9 seems to be dominant in pigs. Persons in direct contact with LA-MRSA-positive animals have an increased risk of becoming MRSA positive. The risk of carriage is mainly related with the intensity of animal contact and with MRSA prevalence among animals on the farm. In contrast with its success in animals, it seemed that MRSA CC398 is a poor persistent colonizer in humans. MRSA ST398 can, however, cause serious (invasive) infections and outbreaks, although, only incidentally reported so far. Farm hygiene and antimicrobial use contributed to MRSA occurrence in animals. Therefore these two determinants should in principle be incorporated into MRSA control programmes in animal production. Like any other microorganism, LA-MRSA is expected to be able to adapt to new hosts and may change over time in the potential to colonize and to produce toxins. Also, the current circulating clone CC398 may be replaced by another clone in Western countries or emerge in countries where this clone is currently low-prevalent. Ongoing MRSA surveillance in humans and animals is needed to detect changes in epidemiology and to implement effective control measures. PMID- 21983339 TI - Gender and racial/ethnic differences in body image development among college students. AB - In the present study we used longitudinal methods to examine body image development during the early part of college. Students (N=390; 54% female) who identified as African American (32%), Latino/a American (27%), and European American (41%) completed surveys during their first, second, and third semesters at college. There were overall gender and racial/ethnic differences in all three aspects of body image, and both stability and change in body image development. Female students' appearance evaluation became more positive, whereas male students' appearance evaluation showed no significant change. Individuals' body areas satisfaction increased over time, but remained stable when controlling for BMI. Appearance orientation did not change, and there were no racial/ethnic differences in body image development. Experiences in the college environment may play a role in these trends. PMID- 21983340 TI - The structure of Arabidopsis thaliana OST1 provides insights into the kinase regulation mechanism in response to osmotic stress. AB - SnRK [SNF1 (sucrose non-fermenting-1)-related protein kinase] 2.6 [open stomata 1 (OST1)] is well characterized at molecular and physiological levels to control stomata closure in response to water-deficit stress. OST1 is a member of a family of 10 protein kinases from Arabidopsis thaliana (SnRK2) that integrates abscisic acid (ABA)-dependent and ABA-independent signals to coordinate the cell response to osmotic stress. A subgroup of protein phosphatases type 2C binds OST1 and keeps the kinase dephosphorylated and inactive. Activation of OST1 relies on the ABA-dependent inhibition of the protein phosphatases type 2C and the subsequent self-phosphorylation of the kinase. The OST1 ABA-independent activation depends on a short sequence motif that is conserved among all the members of the SnRK2 family. However, little is known about the molecular mechanism underlying this regulation. The crystallographic structure of OST1 shows that ABA-independent regulation motif stabilizes the conformation of the kinase catalytically essential alpha C helix, and it provides the basis of the ABA-independent regulation mechanism for the SnRK2 family of protein kinases. PMID- 21983342 TI - Interplay of posttranslational modifications in Sp1 mediates Sp1 stability during cell cycle progression. AB - Although Sp1 is known to undergo posttranslational modifications such as phosphorylation, glycosylation, acetylation, sumoylation, and ubiquitination, little is known about the possible interplay between the different forms of Sp1 that may affect its overall levels. It is also unknown whether changes in the levels of Sp1 influence any biological cell processes. Here, we identified RNF4 as the ubiquitin E3 ligase of Sp1. From in vitro and in vivo experiments, we found that sumoylated Sp1 can recruit RNF4 as a ubiquitin E3 ligase that subjects sumoylated Sp1 to proteasomal degradation. Sp1 mapping revealed two ubiquitination-related domains: a small ubiquitin-like modifier in the N-terminus of Sp1(Lys16) and the C-terminus of Sp1 that directly interacts with RNF4. Interestingly, when Sp1 was phosphorylated at Thr739 by c-Jun NH(2)-terminal kinase 1 during mitosis, this phosphorylated form of Sp1 abolished the Sp1-RNF4 interaction. Our results show that, while sumoylated Sp1 subjects to proteasomal degradation, the phosphorylation that occurs during the cell cycle can protect Sp1 from degradation by repressing the Sp1-RNF4 interaction. Thus, we propose that the interplay between posttranslational modifications of Sp1 plays an important role in cell cycle progression and keeps Sp1 at a critical level for mitosis. PMID- 21983341 TI - Escherichia coli peptide binding protein OppA has a preference for positively charged peptides. AB - The Escherichia coli peptide binding protein OppA is an essential component of the oligopeptide transporter Opp. Based on studies on its orthologue from Salmonella typhimurium, it has been proposed that OppA binds peptides between two and five amino acids long, with no apparent sequence selectivity. Here, we studied peptide binding to E. coli OppA directly and show that the protein has an unexpected preference for basic peptides. OppA was expressed in the periplasm, where it bound to available peptides. The protein was purified in complex with tightly bound peptides. The crystal structure (up to 2.0 A) of OppA liganded with the peptides indicated that the protein has a preference for peptides containing a lysine. Mass spectrometry analysis of the bound peptides showed that peptides between two and five amino acids long bind to the protein and indeed hinted at a preference for positively charged peptides. The preference of OppA for peptides with basic residues, in particular lysines, was corroborated by binding studies with peptides of defined sequence using isothermal titration calorimetry and intrinsic protein fluorescence titration. The protein bound tripeptides and tetrapeptides containing positively charged residues with high affinity, whereas related peptides without lysines/arginines were bound with low affinity. A structure of OppA in an open conformation in the absence of ligands was also determined to 2.0 A, revealing that the initial binding site displays a negative surface charge, consistent with the observed preference for positively charged peptides. Taken together, E. coli OppA appears to have a preference for basic peptides. PMID- 21983343 TI - The therapeutic potential of the recombinant antigen from Dirofilaria immitis (rDiAg) for immune-mediated pregnancy loss. AB - The mammalian fetuses are semi-allograft for mothers. Therefore the failure of immunological tolerance often causes pregnancy loss. Recently, the effects of helminthes therapy for immune mediated diseases have been reported. In the present study we employed the murine model to examine the therapeutic potential of the recombinant antigen from a nematoda parasite, Dirofilaria immitis for immune mediated pregnancy loss. Recombinant D. immitis polyproteins (rDiAg) had been cloned and selected by us for the strongest immuno-regulatory activities in parasite antigens. Female CBA/J mice were injected with sterilized rDiAg or PBS solution using micro-osmotic pumps before mating. Pregnant CBA/J mice were sacrificed on day 13.5 for scoring the number of resorbed and viable fetuses for histological and immunological analysis. The serum cytokine concentrations were measured using suspension array system. The resorption rate of mock-treated mice was 42.9% (resorbed fetus 12/total fetus 28). The resorption rate was decreased to 11.1% (resorbed fetus 3/total fetus 27) with rDiAg treatments. The IL-4, IL-23 and TNF-alpha concentrations in serum were significantly lower in rDiAg-treated mice than mock-treated mice. The serum IL-17 level was also reduced in rDiAg treated mice but the difference was not significant. The rDiAg treatment reduced the resorption rates of CBA/J*DBA/2J mouse model, which mimic human pregnancy failures with allo-immune backgrounds. Our observations suggest as the first time of therapeutic potentials of the rDiAg for pregnancy loss. PMID- 21983344 TI - Imperatorin prevents cardiac hypertrophy and the transition to heart failure via NO-dependent mechanisms in mice. AB - Augmented endothelial nitric oxide (NO) synthase (eNOS) signaling has been reported to be associated with improvements in cardiac remodeling, and NO levels have been shown to be related to cardiac hypertrophy and heart failure. Imperatorin, a dietary furanocoumarin, has been shown to prevent cardiac hypertrophy in the spontaneous hypertension rats (SHR). Thus, we aimed to clarify whether imperatorin attenuates both cardiac hypertrophy and heart failure via the NO-signaling pathway. In neonatal mouse cardiac myocytes, imperatorin inhibited protein synthesis stimulated by either isoproterenol or phenylephrine, which was unchanged by NG-nitro-L-arginine methyl ester (L-NAME). Four weeks after transverse aortic constriction (TAC) on Kunming (KM) male mice, the ratio of heart weight to body weight was lower after imperatorin treatment than in controls (6.60 +/- 0.35 mg/g in TAC, 4.54 +/- 0.29 mg/g with imperatorin 15 mg kg(-1)d(-1), ig, P<0.01); similar changes in the ratio of lung weight to body weight (7.30 +/- 0.85 mg/g in TAC, 5.42 +/- 0.51 mg/g with imperatorin 15 mg kg( 1)d(-1), ig) and the myocardial fibrosis. All of these improvements were blunted by L-NAME. Imperatorin treatment significantly activated phosphorylation of eNOS. Myocardial mRNA levels of natriuretic peptide precursor type B and protein inhibitor of NO synthase, which were increased in the TAC mice, were decreased in the imperatorin-treated ones. Imperatorin can attenuate cardiac hypertrophy both in vivo and in vitro, and halt the process leading from hypertrophy to heart failure by a NO-mediated pathway. PMID- 21983345 TI - Two new abietane diterpenoids from the caulis and leaves of Callicarpa kochiana. AB - Previous studies revealed that diterpenoids from Callicarpa genus were mainly of clerodane-type and phyllocladane-type, and abietane-type diterpenoids were seldom reported. In this paper, we reported two new abietane diterpenoids, kochianic acid A (1) and kochianic acid B (2), together with two known abietane-type diterpenoids, pedunculatic acid B (3) and 7alpha, 15-dihydroxydehydroabietic acid (4), which were all isolated from Callicarpa kochiana. The structures of the new compounds 1 and 2 were elucidated on the basis of extensive spectroscopic analysis, including HSQC, HMBC, (1)H-(1)H COSY, ROESY and finally confirmed by single-crystal X-ray diffraction. PMID- 21983346 TI - Molecular diagnosis of sparganosis associated with pneumothorax in a dog. AB - Pneumothorax was diagnosed in a dog presenting with progressive exercise intolerance and tachypnoea. Needle thoracocentesis failed to resolve the pneumothorax, and an exploratomy thoracotomy was performed. Upon inspection of the thoracic cavity, numerous white nodules (2 to 4mm) were present throughout the mediastinum, parietal pleura and the lung lobes. The owners of the dog elected intra-operative euthanasia, and a post mortem examination was performed. At necropsy, structures consistent with the plerocercoid (larval) stage of a tapeworm were identified in association with inflammation of the pleural cavity. Molecular methods were used to identify the parasite as Spirometra erinacei. Molecular diagnosis, along with the clinical presentation and pathological findings, allowed the diagnosis of proliferative sparganosis. PMID- 21983348 TI - Extended remission of B-cell lymphoma with monoclonal gammopathy in a patient with type 1 Gaucher disease treated with enzyme replacement therapy. PMID- 21983347 TI - Angiopoietin-like-2 and -3 act through their coiled-coil domains to enhance survival and replating capacity of human cord blood hematopoietic progenitors. AB - Several angiopoietin-like (ANGPTL) molecules have been implicated in enhancement of ex-vivo expansion of murine and human (hu) hematopoietic stem cells, but there are no reports on hematopoietic progenitor cells (HPCs). We assessed purified recombinant endotoxin-free hu ANGPTL-2 Coiled-Coil (CC), -3, -3CC, -3 fibrinogen like domain (FLD), -4, -4CC, -5CC, -6 and -7 for effects on proliferation and survival of HPCs from hu cord blood (CB). None of the ANGPTL molecules stimulated CB HPC proliferation, or enhanced or inhibited colony formation of CB HPC stimulated by various growth factors. However, ANGPTL-2CC, -3, and -3CC significantly enhanced survival of HPC (CFU-GM, BFU-E, CFU-GEMM) subjected to delayed addition of growth factors. Survival enhancing effects of ANGPTL-3 were neutralized by purified anti-ANGPTL-3, but not by anti-ANGPTL-4, -6, or -7. ANGPTL-2CC, -3, and -3CC, but not -4, -6, or -7 also enhanced replating capacity of single CB CFU-GEMM colonies, an estimate of the self-renewal capabilities of HPCs, by greater than 2 fold. Effects of at least ANGPTL-3CC may in part be mediated through phosphorylation of ERK. The ANGPTL molecules did not influence ex-vivo expansion of hu CB CD34(+) cells, alone, or in combination with SCF, TPO, Flt3-ligand, with or without IL-3. Thus, among ANGPTL family members, ANGPTL-2 and -3 had enhancing activities on human HPC survival and replating activity, effects requiring the CC domain of the ANGPTL molecules. This information is of relevance to hu HPC regulation. PMID- 21983349 TI - The presence of -308A TNFalpha is associated with anemia and thrombocytopenia in patients with myelodysplastic syndromes. AB - Myelodysplastic syndromes (MDS) constitute a heterogeneous group of clonal hematological diseases characterized by refractory cytopenia(s). MDS patients show increased levels of tumor necrosis factor alpha (TNFalpha) which is a multifunctional proinflammatory cytokine. The aim of this work is to examine the presence of -308A/G TNFalpha variants and to analyze whether it is associated with clinical parameters in a cohort of 101 Argentinean de novo MDS patients. The A/A+A/G genotype at TNFalpha -308 was overrepresented 2-fold in our population (p=0.0499, odds ratio-OR: 2.107) and these differences were more evident in RA FAB subtype (p=0.0424, OR: 2.502). The presence of the high expressing -308A allele was associated with lower hemoglobin level (8.3 vs 9.9g/dL; p=0.0206), reduced platelet counts (89,000 vs 130,000/MUL; p=0.0381) and younger age (59 vs 68years; p=0.0122) at diagnosis. Also, these patients showed 3.8-fold higher risk of transfusion requirement (76% vs 46%, p=0.0105) during the follow up. In conclusion, the presence of an inherited -308A TNFalpha, which increases its transcription level, was associated with the MDS phenotype in our cohort of Argentine MDS patients. Also, an overexpression of TNFalpha may promote an underlying proinflammatory state that cooperates with intrinsic defects within MDS progenitors to increase the severity of certain phenotypic features of the disease. PMID- 21983350 TI - Serotonergic modulation in executive functioning: linking genetic variations to working memory performance. AB - Emerging evidence from studies using, for example, acute tryptophan depletion or investigating genetic variation of genes related to the serotonin signaling pathway suggest a role of serotonin in executive functions such as top-down attention, working memory and inhibitory control. In the current study, we aimed at extending this evidence by using the n-back task to examine working memory performance of 130 participants via behavioral and neurophysiological indices and by focusing on variations within genes encoding key regulators of the serotonergic system: the serotonin transporter gene-linked polymorphic region (5 HTTLPR) and a repeat polymorphism in the transcriptional control region of the monoamine-oxidase gene (MAOA-uVNTR). Because serotonin and norepinephrine systems have been shown to be structurally and functionally highly interrelated, we also examined a novel polymorphism in the promoter region of the norepinephrine transporter gene (NET -3081) in anticipation of epistatic effects. We found that carriers of 5-HTTLPR and MAOA-uVNTR alleles recently implicated in executive processing showed a more efficient executive control of working memory-related performance as evidenced by reaction time, error rate as well as N2 and P3b event related potential measures. This impact was further supported by interactions with the NET polymorphism. Linking serotonergic influence to mechanisms of inhibitory response control implicated in working memory, our results provide further support for and add new evidence concerning the importance of serotonergic neuromodulation in executive functioning. PMID- 21983351 TI - Vomiting as a reliable sign of concussion. AB - Concussion is the most common type of traumatic brain injury, with headache being the most frequent symptom of mild traumatic brain injury (MTBI) (including dizziness, vomiting, nausea, lack of motor coordination or difficulty balancing). Concussion may be caused by a blow to the head, or by acceleration forces without a direct impact. Often, MTBI occurs as the result of a sports injury. Loss of consciousness is always present, unlike vomiting. Therefore, we hypothesize vomiting to be considered as a cardinal sign of concussion. Stimulation of vomiting centres finally triggers vomiting. Professional boxers and mixed martial arts competitions reluctantly agree with stringent rules and protective clothing. We discuss the issue of further protection for those engaged in these and other sports. PMID- 21983352 TI - Circadian desynchrony and metabolic dysfunction; did light pollution make us fat? AB - Circadian rhythms are daily oscillations in physiology and behaviour that recur with a period of 24h, and that are entrained by the daily photoperiod. The cycle of sunrise and sunset provided a reliable time cue for many thousands of years, until the advent of artificial lighting disrupted the entrainment of human circadian rhythms to the solar photoperiod. Circadian desynchrony (CD) occurs when endogenous rhythms become misaligned with daily photoperiodic cycles, and this condition is facilitated by artificial lighting. This review examines the hypothesis that chronic CD that has accompanied the availability of electric lighting in the developed world induces a metabolic and behavioural phenotype that is predisposed to the development of obesity. The evidence to support this hypothesis is based on epidemiological data showing coincidence between the appearance of obesity and the availability of artificial light, both geographically, and historically. This association links CD to obesity in humans, and is corroborated by experimental studies that demonstrate that CD can induce obesity and metabolic dysfunction in humans and in rodents. This association between CD and obesity has far reaching implications for human health, lifestyle and work practices. Attention to the rhythmicity of daily sleep, exercise, work and feeding schedules could be beneficial in targeting or reversing the modern human predisposition to obesity. PMID- 21983353 TI - Obsessive-compulsive tendencies are related to indecisiveness and reliance on feedback in a neutral color judgment task. AB - BACKGROUND AND OBJECTIVES: The present study was designed to test whether OC tendencies are associated with indecisiveness and increased need for objective feedback in vague decision situations. This hypothesis was tested using a neutral color judgment task that places minimal demands on working memory. METHODS: Sixty one participants completed several measures of OC symptoms and tendencies. Indecisiveness was tested on a novel computerized task in which participants can move along a continuum marked by two colors at the extreme ends and are instructed to choose the color they judge to be the exact mid-point on the continuum. RESULTS: OC scores were positively correlated with indecisiveness on the task, as assessed by the amount of time it took participants to complete the task and the extent of their search through the color continuum. This association was most pronounced when feedback for performance was not routinely provided. Requests for feedback were also positively correlated with OC scores. OC scores were not associated with actual performance on the task (accuracy levels) or with confidence ratings. LIMITATIONS: The study relies on non-clinical participants and the extent to which these results would extend to OCD patients in unknown. Some effects may be confounded by the fixed order in which the task phases were administered. CONCLUSIONS: The findings support the hypothesis that OC tendencies are associated with general indecisiveness and reliance on external feedback. PMID- 21983354 TI - Immunogenicity and tolerability of a paediatric presentation of a virosomal hepatitis A vaccine in Chilean children aged 1-16 years. AB - We assessed the immunogenicity of the paediatric dose of Epaxal((r)) (0.25 mL) and the degrees of seroprotection achieved with the standard dose (0.5 mL) of Epaxal((r)) or a dose of Havrix((r)) Junior, in children in an open, randomised, controlled, multi-centre, parallel-group study conducted at 2 Chilean study centres. 360 healthy children and adolescents 12 months to <17 years of age not previously vaccinated against hepatitis A were enrolled. Subjects were randomised 2:2:1 to be vaccinated with either Epaxal((r)) 0.25 mL [n=146], Epaxal((r)) 0.5 mL [n=142] or Havrix((r)) Junior [n=72] intramuscularly on Day 1 and after 6 months (26 weeks+/-14 days). Primary end point was the proportion of subjects seroprotected (anti-HAV antibody concentration >=10 mIU/mL) in the ATP population at Month 1. All vaccines elicited high seroprotection rates at Month 1: 95.7% with Epaxal((r)) 0.25 mL, 99.3% with Epaxal((r)) 0.5 mL and 94.0% with Havrix((r)) Junior. After the booster vaccination, all subjects demonstrated 100% seroprotection with all vaccines. Antibody concentrations were similarly high in all age groups. The paediatric presentation achieved antibody concentrations similar to those achieved with the 0.5 mL dose across the entire age range, and there were no differences across the range of body weights from 9.0 kg to 82.7 kg. All study vaccines were well tolerated and there were no AEs leading to discontinuation. Thus, the paediatric 0.25 mL dose of Epaxal((r)) fulfilled the primary objective of showing non-inferiority to the adult 0.5 mL dose and to Havrix((r)) Junior, in terms of seroprotection rates achieved. The results show the paediatric dose of Epaxal((r)) to be an attractive option when conducting childhood-vaccination programmes. PMID- 21983356 TI - Cervical adenocarcinoma: moving towards better prevention. AB - OBJECTIVE: Although cervical screening has led to a significant decline of invasive cervical cancer (ICC) in developed countries, it remains the third leading cause of cancer in women worldwide. While the majority of the decline in ICC can be attributed to a reduction in squamous cell carcinoma (SCC), the incidence of cervical adenocarcinoma (ADC), absolute and relative to SCC, has been rising steadily, especially in younger women. This paper examines oncogenic human papillomavirus (HPV) infections, the risk of developing cervical ADC and its prognosis. It analyzes differences between ADC and SCC and considers current and future methods for prevention. METHODS: PubMed, publicly available websites and congress abstracts were searched for data and literature. RESULTS: HPV-16, 18 and -45 account for approximately 90% of ADC worldwide. Typically, alpha-7 genotypes, which include HPV-18 and -45, are more commonly associated with ADC than SCC. The difficulty in detecting ADC through screening as well as changing sexual habits and increased HPV transmission may account for its increase; an increase in SCC may not be observed because of improved detection of pre malignant SCC compared with pre-malignant ADC. HPV testing shows promise for screening women >=30years of age, but alpha-7 genotypes may be underrepresented in precancerous lesions. Clinical trial data indicate that current vaccines have high efficacy against HPV-16/18-related cervical intraepithelial neoplasia. Moreover, these vaccines also demonstrate a different level of protection beyond the HPV vaccine types, therefore increasing the overall vaccine efficacy. Such broad coverage could translate into a considerable reduction in the incidence of ADC. CONCLUSION: Prophylactic HPV vaccination may have a significant impact on the prevention of ADC and may significantly impact future strategies for primary and secondary prevention of cervical cancer. PMID- 21983355 TI - A comparison of antibody responses to commercial equine influenza vaccines following primary vaccination of Thoroughbred weanlings--a randomised blind study. AB - Many racing authorities, sales companies and equestrian bodies have mandatory vaccination policies for equine influenza (EI). The consequences of lack of vaccine efficacy include clinical disease, disruption to training programmes, the cancellation of equestrian events and the introduction of virus to susceptible populations. The correlation between antibody against the virus haemagglutinin and protection against influenza has been well established. The objective of this study was to compare the antibody responses of 66 unvaccinated Thoroughbred weanlings on four different stud farms, following primary vaccination (V1, V2 and V3) with the five EI vaccines commercially available in Ireland (Duvaxyn IET Plus, Equilis Resequin, Equip FT, Equilis Prequenza Te, ProteqFlu Te). Antibody responses were monitored for 6 months post V3 by single radial haemolysis. The pattern of antibody response was similar for all vaccines and for all antigens tested. A rapid decline of antibody level was observed by 3 months post V2 for all vaccines. The antibody response of the horses vaccinated with the whole virus vaccine Duvaxyn IET Plus was significantly higher than that of the horses vaccinated with the other four products. Five weanlings had maternally derived antibodies (MDA) at the time of V1. The canary pox recombinant vaccine, subunit vaccine and whole virus inactivated vaccines administered to these weanlings did not induce a detectable antibody response against the background of MDA but effectively primed the animals as revaccination resulted in a strong antibody response. In this study 43% of the weanlings failed to seroconvert after V1. This high incidence of poor responders has not been reported in previous experimental studies relating to these products. The poor responders were observed in all vaccine groups except those vaccinated with Duvaxyn IET Plus. Post V2 the incidence of poor responders was reduced to 7% and all horses responded to V3. The study demonstrates that independent evaluation of influenza vaccine performance in the field is critical to add to the body of knowledge gained from experimental challenge experiments carried out for regulatory or marketing purposes. PMID- 21983357 TI - Immunoglobulin deficiency in children with Hib vaccine failure. AB - Immunoglobulin deficiency has been reported in 21% of UK children with Hib vaccine failure but its clinical significance and long-term consequences are not known. This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection and to determine their risk of recurrent infections. The families of children who developed invasive Hib disease after prior immunisation were identified through national surveillance. A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection, equivalent to 1035 child years of follow-up. Nineteen (11.2%) children had immunoglobulin deficiency, including IgA (n=12), IgM (n=5) and all three immunoglobulin classes (n=2). Immunoglobulin deficiency was associated with younger age (<2 years) at initial Hib disease (12/19 [63.2%] vs. 60/151 [39.7%], P=0.05) and parental reporting of their child receiving >2 antibiotic courses annually in early childhood (11/19 [57.9%] vs. 39/151 [25.8%], P=0.004].). In a logistic regression model, Hib vaccine failure cases that had received multiple antibiotic courses in early childhood were 3.8 times (95% CI, 1.4-10.6; P=0.01) more likely to be immunoglobulin deficient at follow-up than those with fewer or no antibiotic courses. Thus, the prevalence of immunoglobulin deficiency in children with Hib vaccine failure at a median of four years after infection is half that reported at the time of the original infection. A proportion of children with Hib vaccine failure, especially where it occurs at a young age, appear to have a maturational delay in development of normal immunoglobulin concentrations. PMID- 21983359 TI - Transmission of mumps virus from mumps-vaccinated individuals to close contacts. AB - During a recent mumps epidemic in the Netherlands caused by a genotype D mumps virus strain, we investigated the potential of vaccinated people to spread mumps disease to close contacts. We compared mumps viral titers of oral fluid specimens obtained by quantitative PCR from vaccinated (n=60) and unvaccinated (n=111) mumps patients. We also investigated the occurrence of mumps infection among the household contacts of vaccinated mumps patients. We found that viral titers are higher for unvaccinated patients than for vaccinated patients during the 1st 3 days after onset of disease. While no symptomatic cases were reported among the household contacts (n=164) of vaccinated mumps patients (n=36), there were cases with serological evidence of asymptomatic infection among vaccinated household contacts (9 of 66 vaccinated siblings). For two of these siblings, the vaccinated index patient was the most probable source of infection. We conclude that, in this particular outbreak, the risk of a close contact becoming infected by vaccinated patients was small, but present. PMID- 21983358 TI - The attenuated NYCBH vaccinia virus deleted for the immune evasion gene, E3L, completely protects mice against heterologous challenge with ectromelia virus. AB - The New York City Board of Health (NYCBH) vaccinia virus (VACV) vaccine strain was deleted for the immune evasion gene, E3L, and tested for its pathogenicity and ability to protect mice from heterologous challenge with ectromelia virus (ECTV). NYCBHDeltaE3L was found to be highly attenuated for pathogenicity in a newborn mouse model and showed a similar attenuated phenotype as the NYVAC strain of vaccinia virus. Scarification with one or two doses of the attenuated NYCBHDeltaE3L was able to protect mice equally as well as NYCBH from death, weight loss, and viral spread to visceral organs. A single dose of NYCBHDeltaE3L resulted in low poxvirus-specific antibodies, and a second dose increased levels of poxvirus-specific antibodies to a level similar to that seen in animals vaccinated with a single dose of NYCBH. However, similar neutralizing antibody titers were observed following one or two doses of NYCBHDeltaE3L or NYCBH. Thus, NYCBHDeltaE3L shows potential as a candidate for a safer human smallpox vaccine since it protects mice from challenge with a heterologous poxvirus. PMID- 21983360 TI - Immunization with the RTS,S/AS malaria vaccine induces IFN-gamma(+)CD4 T cells that recognize only discrete regions of the circumsporozoite protein and these specificities are maintained following booster immunizations and challenge. AB - In a Phase 2a trial of the RTS,S/AS vaccine, we described significant association between protection against infection and vaccine-induced CD4 T cells. To determine whether processing of the circumsporozoite protein as a component of the RTS,S particulate antigen yields the same HLA-DR-restricted epitopes as those recognized by CD4 T cells from donors immunized by exposure to attenuated or infectious sporozoites we mapped the specificities of the RTS,S primed CD4 T cells by measuring IFN-gamma cultured Elispot responses to pairs of overlapping 15 a.a. peptides that span the protein's C-terminus. Peptide pairs representing the previously described TH2R, T* and CS.T3 epitopes, were immunoprevalent and immunodominant. There was no response to the peptides corresponding to the human thrombospondin homology region. Responses to the CD4 T cell epitopes were restricted by multiple HLA-DR haplotypes. Of note, HLA-DR4 and HLA-DR11 restricted epitopes in the T* region and in the location on the CS protein defined by peptide pair 4, respectively. We conclude that processing of the CS protein derived from the RTS,S antigen leads to the generation of HLA-DR restricted epitopes that are similar to those identified previously using CD4 T cells from subjects immunized with and protected by attenuated sporozoites or exposed to infectious sporozoites. This may in part account for the protective efficacy of the RTS,S/AS vaccine. PMID- 21983361 TI - Effectiveness of the new serotypes in the 13-valent pneumococcal conjugate vaccine. AB - Efficacy of the new serotypes in the 13-valent pneumococcal conjugate vaccine (PCV13) against invasive pneumococcal disease (IPD) was based on a putative correlate of protection. In England and Wales, PCV13 replaced PCV7 in the 2, 4, and 13 month schedule in April 2010. Using non-vaccine type IPD cases as controls, we estimated vaccine effectiveness (VE) for the new serotypes. Among 166 IPD cases in PCV13 eligible children reported by July 2011 with known serotype and vaccination status, VE for 2 doses under a year was 78% (95% confidence interval -18% to 96%) and 77% (38-91%) for one dose over a year. VE for 7F and 19A was 76% (21-93%) and 70% (10-90%) respectively for >=one dose. VE for serotypes 1 and 3 was 62% and 66% respectively although confidence intervals spanned zero. IPD due to PCV13-only serotypes halved in children under 2 years in the study period. PMID- 21983362 TI - Immunological responses induced by a DNA vaccine expressing RON4 and by immunogenic recombinant protein RON4 failed to protect mice against chronic toxoplasmosis. AB - The development of an effective vaccine against Toxoplasma gondii infection is an important issue due to the seriousness of the related public health problems, and the economic importance of this parasitic disease worldwide. Rhoptry neck proteins (RONs) are components of the moving junction macromolecular complex formed during invasion. The aim of this study was to evaluate the vaccine potential of RON4 using two vaccination strategies: DNA vaccination by the intramuscular route, and recombinant protein vaccination by the nasal route. We produced recombinant RON4 protein (RON4S2) using the Schneider insect cells expression system, and validated its antigenicity and immunogenicity. We also constructed optimized plasmids encoding full length RON4 (pRON4), or only the N terminal (pNRON4), or the C-terminal part (pCRON4) of RON4. CBA/J mice immunized with pRON4, pNRON4 or pCRON4 plus a plasmid encoding the granulocyte-macrophage colony-stimulating factor showed high IgG titers against rRON4S2. Mice immunized by the nasal route with rRON4S2 plus cholera toxin exhibited low levels of anti RON4S2 IgG antibodies, and no intestinal IgA antibodies specific to RON4 were detected. Both DNA and protein vaccination generated a mixed Th1/Th2 response polarized towards the IgG1 antibody isotype. Both DNA and protein vaccination primed CD4+ T cells in vivo. In addition to the production of IFN-gamma, and IL 2, Il-10 and IL-5 were also produced by the spleen cells of the immunized mice stimulated with RON4S2, suggesting that a mixed Th1/Th2 type immune response occurred in all the immunized groups. No cytokine was detectable in stimulated mesenteric lymph nodes from mice immunized by the nasal route. Immune responses were induced by both DNA and protein vaccination, but failed to protect the mice against a subsequent oral challenge with T. gondii cysts. In conclusion, strategies designed to enhance the immunogenicity and to redirect the cellular response towards a Th1 type response against RON4 could lead to more encouraging results. PMID- 21983363 TI - Construction of a non-toxigenic Escherichia coli oral vaccine strain expressing large amounts of CS6 and inducing strong intestinal and serum anti-CS6 antibody responses in mice. AB - Coli surface antigen 6 (CS6) is one of the most prevalent non-fimbrial colonization factors (CFs) of enterotoxigenic Escherichia coli (ETEC) bacteria, which are the most common cause of diarrhea among infants and children in developing countries. Since immune protection against ETEC is mainly mediated by locally produced IgA antibodies in the gut, much effort is focused on the development of an oral CF-based vaccine. Previous work has described the preparation of candidate E. coli vaccine strains expressing immunogenic amounts of fimbrial CF antigens such as CFA/I and CS2, which are retained after formalin treatment. However, attempts to generate E. coli expressing immunogenic amounts of CS6 and to preserve the immunological activity of the CS6 protein in a killed whole-cell vaccine have failed until now. Here we describe the construction of a recombinant non-toxigenic E. coli strain, with thyA as a non-antibiotic-based selection, which expresses large amounts of CS6 antigen on the bacterial surface, and show that phenol inactivation of the bacteria does not destroy the CS6 antigen properties. Oral immunization of mice with such phenol-killed CS6 over expressing E. coli bacteria induced strong fecal and intestinal IgA and serum IgG+IgM antibody responses to CS6 that exceeded the responses induced by an ETEC reference strain naturally expressing CS6 and previously used as a vaccine strain. Our data indicate that the described phenol-inactivated non-toxigenic and CS6 over-expressing E. coli strain may be a useful component in an oral ETEC vaccine. PMID- 21983364 TI - Single wire radial junction photovoltaic devices fabricated using aluminum catalyzed silicon nanowires. AB - Single nanowire radial junction solar cell devices were fabricated using Si nanowires synthesized by Al-catalyzed vapor-liquid-solid growth of the p(+) core (Al auto-doping) and thin film deposition of the n(+)-shell at temperatures below 650 degrees C. Short circuit current densities of 11.7 mA cm(-2) were measured under 1-sun AM1.5G illumination, showing enhanced optical absorption. The power conversion efficiencies were limited to < 1% by the low open circuit voltage and fill factor of the devices, which was attributed to junction shunt leakage promoted by the high p(+)/n(+) doping. This demonstration of a radial junction device represents an important advance in the use of Al-catalyzed Si nanowire growth for low cost photovoltaics. PMID- 21983365 TI - Prediction of time of death after withdrawal of life-sustaining treatment in potential donors after cardiac death*. AB - OBJECTIVE: Organ donation after cardiac death increases the number of donor organs. In controlled donation after cardiac death donors, the period between withdrawal of life-sustaining treatment and cardiac arrest is one of the parameters used to assess whether organs are suitable for transplantation. The objective of this study was to identify donation after cardiac death donor characteristics that affect the interval between withdrawal of life-sustaining treatment and cardiac death. DESIGN: Prospective multicenter study of observational data. PATIENTS: All potential donation after cardiac death donors in The Netherlands between May 2007 and June 2009 were identified. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 242 potential donation after cardiac death donors, 211 entered analysis, 76% of them died within 60 mins, and 83% died within 120 mins after withdrawal of life-sustaining treatment. The median time to death was 20 mins (range 1 min to 3.8 days). Controlled mechanical ventilation, use of norepinephrine, absence of reflexes, neurologic deficit as cause of death, and absence of cardiovascular comorbidity were associated with death within 60 and 120 mins. The use of analgesics, sedatives, or extubation did not significantly influence the moment of death. In the multivariable logistic regression analysis, controlled mechanical ventilation remained a risk factor for death within 60 mins, and norepinephrine administration and absence of cardiovascular comorbidity remained risk factors for death within 120 mins. The clinical judgment of the intensivist predicted death within 60 and 120 mins with a sensitivity of 73% and 89%, respectively, and a specificity of 56% and 25%, respectively. CONCLUSION: Despite the identification of risk factors for early death and the additional value of the clinical judgment by the intensivist, it is not possible to reliably identify potential donation after cardiac death donors who will die within 1 or 2 hrs after life-sustaining treatment has been withdrawn. Consequently, a donation procedure should be initiated in every potential donor. PMID- 21983366 TI - The impact of a lean rounding process in a pediatric intensive care unit. AB - INTRODUCTION/OBJECTIVE: Poor workflow associated with physician rounding can produce inefficiencies that decrease time for essential activities, delay clinical decisions, and reduce staff and patient satisfaction. Workflow and provider resources were not optimized when a pediatric intensive care unit increased by 22,000 square feet (to 33,000) and by nine beds (to 30). Lean methods (focusing on essential processes) and scenario analysis were used to develop and implement a patient-centric standardized rounding process, which we hypothesize would lead to improved rounding efficiency, decrease required physician resources, improve satisfaction, and enhance throughput. DESIGN: Human factors techniques and statistical tools were used to collect and analyze observational data for 11 rounding events before and 12 rounding events after process redesign. Actions included: 1) recording rounding events, times, and patient interactions and classifying them as essential, nonessential, or nonvalue added; 2) comparing rounding duration and time per patient to determine the impact on efficiency; 3) analyzing discharge orders for timeliness; 4) conducting staff surveys to assess improvements in communication and care coordination; and 5) analyzing customer satisfaction data to evaluate impact on patient experience. SETTING: Thirty-bed pediatric intensive care unit in a children's hospital with academic affiliation. PATIENTS/SUBJECTS: Eight attending pediatric intensivists and their physician rounding teams. INTERVENTIONS: Eight attending physician-led teams were observed for 11 rounding events before and 12 rounding events after implementation of a standardized lean rounding process focusing on essential processes. MEASUREMENTS AND MAIN RESULTS: Total rounding time decreased significantly (157 +/- 35 mins before vs. 121 +/- 20 mins after), through a reduction in time spent on nonessential (53 +/- 30 vs. 9 +/- 6 mins) activities. The previous process required three attending physicians for an average of 157 mins (7.55 attending physician man-hours), while the new process required two attending physicians for an average of 121 mins (4.03 attending physician man hours). Cumulative distribution of completed patient rounds by hour of day showed an improvement from 40% to 80% of patients rounded by 9:30 AM. Discharge data showed pediatric intensive care unit patients were discharged an average of 58.05 mins sooner (p < .05). Staff surveys showed a significant increase in satisfaction with the new process (including increased efficiency, improved physician identification, and clearer understanding of process). Customer satisfaction scores showed improvement after implementing the new process. CONCLUSIONS: Implementation of a lean-focused, patient-centric rounding structure stressing essential processes was associated with increased timeliness and efficiency of rounds, improved staff and customer satisfaction, improved throughput, and reduced attending physician man-hours. PMID- 21983367 TI - A comparison of the performance of a model based on administrative data and a model based on clinical data: effect of severity of illness on standardized mortality ratios of intensive care units. AB - OBJECTIVES: It has been postulated that prognostic models based on administrative data can provide valid adjusted mortality rates in specific patient populations. In this study we compared the performance and robustness of a model based on administrative data (customized hospital standardized mortality ratio) and a model based on clinical data (customized Simplified Acute Physiology Score II) in the Dutch intensive care unit population. DESIGN: Cohort study of intensive care unit records from a national intensive care unit quality registry linked to administrative records from the Dutch National Medical Registration. The hospital standardized mortality ratio and Simplified Acute Physiology Score II models were first-level customized on the intensive care unit population. SETTING: Fifty-five Dutch intensive care units. PATIENTS: A total of 66,564 intensive care unit patients admitted from 2005 to 2008. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Performance expressed by measures of discrimination, accuracy, and calibration (area under the receiver operating characteristic curve, Brier score, Hosmer-Lemeshow C-statistic, and calibration plots). Additionally, the robustness of the models was assessed by simulating changes in the population's severity of illness and analyzing the effect on the intensive care units' standardized mortality ratios.The area under the receiver operating characteristic curve and Brier score of the customized Simplified Acute Physiology Score II were significantly superior to that of the customized hospital standardized mortality ratio (0.85 and 0.11 vs. 0.77 and 0.13, respectively). Calibration plots showed good agreement between observed and predicted mortality for low-risk patients in both models, with more discrepancy in the high-risk patients when using the customized hospital standardized mortality ratio. Severity of illness had influence on the intensive care units' standardized mortality ratios in both models, but the customized Simplified Acute Physiology Score II showed more robustness. CONCLUSIONS: The customized Simplified Acute Physiology Score II outperforms the customized hospital standardized mortality ratio in the Dutch intensive care unit population. Comparing institutions based on standardized mortality ratios can be unfavorable for those with a more severely ill intensive care unit population, especially when using the customized hospital standardized mortality ratio. PMID- 21983368 TI - Use of the impedance threshold device improves survival rate and neurological outcome in a swine model of asphyxial cardiac arrest*. AB - OBJECTIVE: To assess whether intermittent impedance of inspiratory gas exchange improves hemodynamic parameters, 48-hr survival, and neurologic outcome in a swine model of asphyxial cardiac arrest treated with active compression decompression cardiopulmonary resuscitation. DESIGN: Prospective, randomized, double-blind study. SETTING: Laboratory investigation. SUBJECTS: Thirty healthy Landrace/Large-White piglets of both sexes, aged 10 to 15 wks, whose average weight was 19 +/- 2 kg. INTERVENTIONS: At approximately 7 mins following endotracheal tube clamping, ventricular fibrillation was induced and remained untreated for another 8 mins. Before initiation of cardiopulmonary resuscitation, animals were randomly assigned to either receive active compression-decompression cardiopulmonary resuscitation plus a sham impedance threshold device (control group, n = 15), or active compression-decompression cardiopulmonary resuscitation plus an active impedance threshold device (experimental group, n = 15). Electrical defibrillation was attempted every 2 mins until return of spontaneous circulation or asystole. MEASUREMENTS AND MAIN RESULTS: Return of spontaneous circulation was observed in six (40%) animals treated with the sham valve and 14 (93.3%) animals treated with the active valve (p = .005, odds ratio 21.0, 95% confidence interval 2.16-204.6). Neuron-specific enolase and S-100 levels increased in the ensuing 4 hrs post resuscitation in both groups, but they were significantly elevated in animals treated with the sham valve (p < .01). At 48 hrs, neurologic alertness score was significantly better in animals treated with the active valve (79.1 +/- 18.7 vs. 50 +/- 10, p < .05) and was strongly negatively correlated with 1- and 4-hr postresuscitation neuron-specific enolase (r = -.86, p < .001 and r = -.87, p < .001, respectively) and S-100 (r = -.77, p < .001 and r = -0.8, p = .001) values. CONCLUSIONS: In this model of asphyxial cardiac arrest, intermittent airway occlusion with the impedance threshold device during the decompression phase of active compression-decompression cardiopulmonary resuscitation significantly improved hemodynamic parameters, 24- and 48-hr survival, and neurologic outcome evaluated both with clinical and biochemical parameters (neuron-specific enolase, S-100). PMID- 21983369 TI - Systemic release of cytokines and heat shock proteins in porcine models of polytrauma and hemorrhage*. AB - OBJECTIVE: To define systemic release kinetics of a panel of cytokines and heat shock proteins in porcine polytrauma/hemorrhage models and to evaluate whether they could be useful as early trauma biomarkers. DESIGN: Prospective observational study. SETTING: Research laboratory. SUBJECTS: Twenty-one Yorkshire pigs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pigs underwent polytrauma (femur fractures/lung contusion, P), hemorrhage (mean arterial pressure 25-30 mm Hg, H), polytrauma plus hemorrhage (P/H), or sham procedure (S). Plasma was obtained at baseline, in 5- to 15-min intervals during a 60-min shock period without intervention, and in 60- to 120-min intervals during fluid resuscitation for up to 300 min. Plasma was assayed for interleukin-1beta, interleukin-4, interleukin-5, interleukin-6, interleukin-8, interleukin-10, interleukin-12/interleukin-23p40, interleukin-13, interleukin-17, interleukin-18, interferongamma, transforming growth factor-beta, tumor necrosis factor-alpha, heat shock protein 40, heat shock protein 70, and heat shock protein 90 by enzyme linked immunosorbent assay. All animals after S, P, and H survived (n = 5/group). Three of six animals after P/H died. Interleukin-10 increased during shock after P and this increase was attenuated after H. Tumor necrosis factor-alpha increased during the shock period after P, H, and also after S. P/H abolished the systemic interleukin-10 and tumor necrosis factor-alpha release and resulted in 20% to 30% increased levels of interleukin-6 during shock. As fluid resuscitation was initiated, tumor necrosis factor-alpha and interleukin-10 levels decreased after P, H, and P/H; heat shock protein 70 increased after P; and interleukin-6 levels remained elevated after P/H and also increased after P and S. CONCLUSIONS: Differential regulation of the systemic cytokine release after polytrauma and/or hemorrhage, in combination with the effects of resuscitation, can explain the variability and inconsistent association of systemic cytokine/heat shock protein levels with clinical variables in trauma patients. Insults of major severity (P/H) partially suppress the systemic inflammatory response. The plasma concentrations of the measured cytokines/heat shock proteins do not reflect injury severity or physiological changes in porcine trauma models and are unlikely to be able to serve as useful trauma biomarkers in patients. PMID- 21983370 TI - Effect of the bevel direction of puncture needle on success rate and complications during internal jugular vein catheterization. AB - OBJECTIVE: Artery puncture and hematoma formation are the most common immediate complications during internal jugular vein catheterization. This study was performed to assess whether the bevel-down approach of the puncture needle decreases the incidence of posterior venous wall damage and hematoma formation during internal jugular vein catheterization. DESIGN: Prospective, randomized, controlled study. SETTING: A university-affiliated hospital. PATIENTS: Three hundred thirty-eight patients for scheduled for thoracic surgery requiring central venous catheterization in the right internal jugular vein. INTERVENTIONS: Patients requiring internal jugular vein catheterization were enrolled and randomized to either the bevel-down group (n = 169) or the bevel-up group (n = 169). All patients were placed in the Trendelenburg position with the head turned to the left. After identifying the right internal jugular vein with ultrasound imaging, a double-lumen central venous catheter was inserted using the modified Seldinger technique. Venous entry of the needle was recognized by return of venous blood during needle advance or withdrawal. The internal jugular vein was assessed cross-sectionally and longitudinally after catheterization to identify any complications. A p value of <.05 was considered to be statistically significant. MEASUREMENTS AND MAIN RESULTS: There was no difference in the incidence of the puncture-on-withdrawal between the two groups (37 of 169 in the bevel-down group and 25 of 169 in the bevel-up group). However, the incidence of posterior hematoma formation was lower in the bevel-down group (six of 169 vs. 17 of 169, p = .031). Additionally, there was less incidence of the posterior hematoma formation associated with puncture-on-withdrawal in the bevel-down group (six of 37 vs. 11 of 25, p = .034). CONCLUSIONS: The bevel-down approach of the right internal jugular vein may decrease the incidence of posterior venous wall damage and hematoma formation compared with the bevel-up approach, which implicates a reduced probability of carotid artery puncture with the bevel-down approach during internal jugular vein catheterization. PMID- 21983371 TI - Effects of methylprednisolone infusion on markers of inflammation, coagulation, and angiogenesis in early acute respiratory distress syndrome. AB - OBJECTIVE: Evaluate the effects of methylprednisolone on markers of inflammation, coagulation, and angiogenesis during early acute respiratory distress syndrome. DESIGN: Retrospective analysis. SETTING: Four intensive care units. SUBJECTS: Seventy-nine of 91 patients with available samples enrolled in a randomized, blinded controlled trial. INTERVENTIONS: Early methylprednisolone infusion (n = 55) compared with placebo (n = 24). MEASUREMENTS AND MAIN RESULTS: Interleukin-6, tumor necrosis factor alpha, vascular endothelial growth factor, protein C, procalcitonin, and proadrenomedullin were measured in archived plasma. Changes from baseline to day 3 and day 7 were compared between groups and in subgroups based on the precipitating cause of acute respiratory distress syndrome. Methylprednisolone therapy was associated with greater improvement in Lung Injury Score (p = .003), shorter duration of mechanical ventilation (p = .005), and lower intensive care unit mortality (p = .05) than control subjects. On days 3 and 7, methylprednisolone decreased interleukin-6 and increased protein C levels (all p < .0001) compared with control subjects. Proadrenomedullin levels were lower by day 3 with methylprednisolone treatment (p = .004). Methylprednisolone decreased interleukin-6 by days 3 and 7 in patients with pulmonary causes of acute respiratory distress syndrome but only at day 3 in those with extrapulmonary causes of acute respiratory distress syndrome. Protein C levels were increased with methylprednisolone on days 3 and 7 in patients with infectious and/or pulmonary causes of acute respiratory distress syndrome (all p < .0001) but not in patients with noninfectious or extrapulmonary causes of acute respiratory distress syndrome. Proadrenomedullin levels were decreased with methylprednisolone on day 3 in patients with infectious or extrapulmonary causes of acute respiratory distress syndrome (both p <= .008) but not in noninfectious or pulmonary acute respiratory distress syndrome. Tumor necrosis factor, vascular endothelial growth factor, and procalcitonin were elevated but not differentially affected by methylprednisolone therapy. CONCLUSIONS: In early acute respiratory distress syndrome, administration of methylprednisolone was associated with improvement in important biomarkers of inflammation and coagulation and clinical outcomes. Biomarker changes varied with the precipitating cause of acute respiratory distress syndrome, suggesting that the underlying mechanisms and response to anti-inflammatory therapy may vary with the cause of acute respiratory distress syndrome. PMID- 21983372 TI - Obsessive-compulsive disorder. AB - This review article addresses obsessive-compulsive disorder from the prospective of information that is relevant to general practitioners, family physicians, and other medical health specialists, focusing on epidemiology, etiology, diagnostic criteria, comorbidity, and a summary of well recognized treatment modalities and approaches that are available to treat this condition. PMID- 21983373 TI - Relation between serum magnesium level and migraine attacks. AB - OBJECTIVE: The determination of serum magnesium levels in migraine. METHODS: In a case control study performed between January 2007 and December 2007 at Tabriz University of Medical Sciences, Tabriz, Iran, 140 migraine patients were enrolled and their level of serum magnesium was determined and the results were compared with 140 healthy people who did not have any headache, kidney, or gastrointestinal disorders, and no consumption of magnesium complements. RESULTS: Migraine patients (22 male, 118 female) with a mean age of 33.82+/-10.31 and 140 healthy people (26 male, 114 female) with a mean age of (34.19+/-9.95) were enrolled. Forty patients had aura and 100 patients did not have aura. The average serum magnesium level in the patient group (26.14+/-4.3) was significantly lower than the control (31.09+/-4.32) group (p=0.000). There was no significant difference between the mean level of serum magnesium in patients with migraine with aura and without aura, however, there was a significant linear relationship between the amount of serum magnesium and the frequency of headache. CONCLUSION: Serum magnesium in migraine patients was significantly lower than the normal population and related to the frequency of migraine attacks, supporting the use of magnesium in prevention and treatment of migraine. PMID- 21983374 TI - Relationship between the interval before high-dose methylprednisolone administration and chronic pain in traumatic spinal cord injury. AB - OBJECTIVE: To examine the relationship between the interval before the administration of high-dose methylprednisolone (MP) and pain in traumatic spinal cord injury (SCI) patients. METHODS: We retrospectively studied the medical records of admitted patients with traumatic SCI at the Department of Physical Medicine and Rehabilitation, Tri- Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan from January 2005 to January 2010. We examined the relationship between the interval before the administration of highdose MP, and the severity of pain and the presence of neuropathic pain (NeP). Patients treated with highdose MP <8 hours after their injuries were defined as the classical-MP group (n=22), and patients who received high-dose MP >/-8 hours after their injuries were defined as the delayed-MP group (n=10). The patients were mailed questionnaires including the Short-Form McGill Pain Questionnaire (SF-MPQ), and the Douleur Neuropathique 4 Questions questionnaire (DN4Q). RESULTS: The SF-MPQ score in the classical-MP group (9.54 +/- 10.4) was almost 2-fold more than in the delayed-MP group (5.9 +/- 3.5). The interval before the administration of high-dose MP was positively correlated with the DN4Q and SF-MPQ scores, although these differences, and associations were not statistically significant. The increased interval in the administration of MP resulted in slightly greater pain and an increased prevalence of NeP. CONCLUSION: Although the delayed administration of high-dose MP did not significantly increase the severity of pain or prevalence of NeP, it should still be avoided due to the increased risk of serious side effects. PMID- 21983375 TI - Cerebral venous sinus thrombosis in Saudi Arabia. AB - OBJECTIVE: To analyze the clinical patterns, etiologies, treatment, and outcome of cerebral venous sinus thrombosis (CVST) in 2 major cities of Saudi Arabia, Jeddah and Al-Baha. METHODS: One hundred and eleven patients diagnosed as CVST were identified from the medical records at King Abdulaziz Medical City, Jeddah, and King Fahad Hospital, Al-Baha, Saudi Arabia, from January 1990 through November 2010. We retrospectively analyzed the data, compared it with local and international studies, and reviewed the literature. RESULTS: There were 92 adults and 19 children. Among adults, females predominated, while more boys were affected than girls. The mean age of onset was 29.5 years. The most common clinical presentations were headache, focal neurologic deficits, seizures, papilledema, and decreased level of consciousness. The main risk factors identified were pregnancy/ puerperium, antiphospholipid antibody syndrome, oral contraceptive pills, malignancy, and infections. Multiple sinuses were affected in 51 patients (45.9%). When a single sinus was involved, the superior sagittal sinus (24.3%) was the most common. Seventy-four patients recovered completely, 23 patients recovered partially, and 10 patients died. Bad prognostic factors included incurable co-morbid conditions, late presentation, and status epilepticus. CONCLUSION: Pregnancy/puerperium was the most common etiological factor in our series. Clinical features were similar to international series. Behcet's disease was not a major etiological factor in our series. Most patients had involvement of multiple sinuses. Prompt treatment with anticoagulation resulted in complete or partial recovery in 87.4% of patients. PMID- 21983376 TI - Use of antiplatelets. A survey of secondary prevention of ischemic stroke with intracranial hemorrhage history in Chinese patients. AB - OBJECTIVE: To explore whether antiplatelet (AP) agent therapy increased intracranial hemorrhage (ICH) incidence and reduced ischemic stroke recurrence. METHODS: A single-center retrospective cohort study involving 256 cases from 336 Chinese in-patients who had ischemic stroke with ICH history in Beijing Chaoyang Hospital, Beijing, China between May 2005 and October 2009 was conducted. Subjects were divided into 2 groups (with AP and without AP), followed by stroke events for 12-38 months. Logistic regression analysis was used to evaluate the effects of AP on cerebral infarction and ICH recurrence. RESULTS: The AP agent did not increase ICH recurrence in the secondary prevention of ischemic stroke with ICH history (odds ratio [OR] 1.431, confidence interval [CI] 0.198-2.467, p=0.577). Hypertension and lobar hemorrhage were risk factors of ICH recurrence. However, there was no statistical difference between recurrence of lobar hemorrhage and AP use (x2=0.516, p=0.468). The AP agent significantly decreased the incidence of cerebral infarction (OR 0.424, CI 0.190-0.950, p=0.037). CONCLUSION: The AP agents may be beneficial to secondary prevention of ischemic stroke with ICH history, with no increased incidence of cerebral hemorrhage. It would be safer to maintain blood pressure in the normal range and to exclude lobar hemorrhage when AP is used. PMID- 21983377 TI - Characteristics of circadian rhythm in patients with intracerebral hemorrhage before death. AB - OBJECTIVE: To investigate characteristics of circadian rhythm in intracerebral hemorrhage before death. METHODS: This retrospective study was carried out from September 2002 to February 2009. One hundred and twenty-two dead cases with intracerebral hemorrhage(ICH) were collected. The study was carried out in the Department of Neurosurgery in The Second Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China. Blood pressure (BP) and heart rate (HR) were recorded every half-hour during the 72 hours before death. Data of BP and HR before deaths were divided into 3 time periods, namely, period A (72-48 hours to death), period B (48-24 hours to death), and period C (24 hours to death). Data from the 3 periods were analyzed using the Cosinor method to determine whether circadian rhythm was present or absent. The cases were divided into a present and absent group after Cosinor analysis. Prognostic factors in the 2 groups were analyzed by Student's t-test and Pearson's chi-squared test. RESULTS: Significant differences in prognostic factors between the 2 groups were not found. When circadian midline-estimating statistic of rhythms over the 3 periods were compared, there were no significant differences. However, when circadian amplitudes over the 3 periods were compared, the amplitudes during period C were significantly lower than period A or B (p<0.001). The percentage of cases in the absent and present groups was significantly different (p<0.001) over the 3 periods. CONCLUSION: As an independent factor, circadian variation could predict death in patients with ICH. PMID- 21983378 TI - Epidemiology of attempted suicide in Hatay, Turkey. AB - OBJECTIVE: To determine suicide rates, sociodemographic risk factors, and reasons for suicide attempts. METHODS: This hospital based, retrospective study consisted of 1613 suicide attempts brought to the emergency services of 8 state hospitals in Hatay, Turkey from January 2007 to December 2009. We obtained the data by retrospective analysis of patient record forms including information on age, gender, education level, marital status, occupation, reason for suicide, method of suicide, presence of previous psychiatric disease in the patient or family, previous suicidal behavior in the patient or family. We obtained current population data of the province from the Turkish State Institute of Statistics. Chi-Square test, and percentage distribution was used for the statistical analysis. RESULTS: The mean age of females (23.9+/-7.9) was lower than males (26.6+/-9.7). The mean annual rate of attempted suicides per 100,000 was 38.14 (16.11 in males, 60.42 in females). The rate decreased as the age increased, and was highest in the 15-24 age group, in women, in non-married patients, and in the individuals with high school education. Self-poisoning with a drug overdose was the most common method, and domestic conflicts were the most common reason. Psychiatric disease history in the family or patient, and suicide attempt in the family were risk factors associated with repeated suicide attempts. CONCLUSION: The suicide attempt rate was lower than in many western countries, and similar to previous studies in Turkey. The risk of recurrence in suicide attempts is high, and is associated with psychosocial factors. PMID- 21983379 TI - Degree of dependence influences the effects of smoking on psychomotor performance and working memory capacity. AB - OBJECTIVE: Exploration of the variable effect of the degree of smoking dependence on psychomotor performance and working memory capacity. METHODS: This is a randomized, controlled, prospective study conducted in the Department of Pharmacology, College of Medicine, Al-Mustansiriya University, Baghdad, Iraq from 15 January 2011 to 25 February 2011. After third stage male medical students completed the Fagerstrom Test for Nicotine Dependence questionnaire, we randomly selected a sample of 32 students and divided them into 3 groups: 10 participants with zero score (non-smokers), 11 participants with a score of 5 or less (light smokers), and 11 participants with a score of 6 or more (heavy smokers). Choice reaction time and flicker fusion were measured by the Leeds psychomotor performance test battery, and working memory capacity was measured by the N-back working memory test. RESULTS: We found significant improvement in ascending flicker fusion test in heavy smokers in comparison with non-smokers (p=0.005, confidence interval [CI] 0.99-6), and light smokers (p=0.053, CI 0.39-4.5). Heavy smokers significantly deteriorated in the 3-back task in comparison with non smokers (p=0.006, CI 4-25.8), and light smokers (p=0.009, CI 3-24.4). No significant changes were seen between groups in the descending critical flicker fusion, the components of choice reaction time, and in 1-, 2- back working memory tests. CONCLUSION: Heavy smoking (high nicotine) enhances arousal, but impairs working memory capacity. PMID- 21983380 TI - Stereological volumetric evaluation of the cerebellum in benign paroxysmal positional vertigo. AB - OBJECTIVE: To evaluate cerebellar volume changes and the asymmetry of patients with benign paroxysmal positional vertigo (BPPV). METHODS: The cerebellar hemispheres' volumetric symmetry were evaluated using a stereological method on MR images. The study included 15 patients with BPPV, and 14 age-, and gender matched control subjects. The cases were admitted to the Departments of Otolaryngology, Neurology, and Neurosurgery in the Faculty of Medicine, Kocatepe University, Afyonkarahisar, Turkey with the complaint of vertigo between January 2004 and December 2008. RESULTS: The right hemi cerebellum volumes of the subjects with BPPV and the controls were measured smaller than the left hemi cerebellar volumes, however, there was no statistically significant quantitative evidence detected in terms of cerebellar asymmetry between sagittal and axial plane estimates in the cases with vertigo. There was statistical significance between the right and left cerebellum in both the patient and control groups (p=0.023), however, the difference did not change according to gender. There were no statistically significant age and gender dependent cerebellar atrophy and asymmetry between BPPV and control subjects. CONCLUSION: There was no cerebellar atrophy and asymmetry between BPPV and age matched control groups. The stereological evaluation of hemi cerebellar symmetry and atrophy in humans is important for both clinicians and anatomists. The technique is simple, inexpensive, and reliable. PMID- 21983381 TI - Giant occipital osteoid osteoma mimicking calcified meningioma. AB - Osteoid osteoma is a benign bone tumor, which rarely occurs in the skull, and often causes local pain that is worse at night, characteristically relieved by aspirin. Giant osteoid osteoma in the occipital bone is uncommon. We present a case of a 42-year-old female with an osteoid osteoma of the occipital bone that was totally resected. We discuss the clinical presentation, radiographic findings, and differential diagnosis of occipital osteoid osteoma. PMID- 21983382 TI - Intradural lumbar cystic schwannoma. AB - Intradural lumbar cystic schwannomas are a very rare entity and only 10 case reports have been reported in the literature. The diagnosis and management remains a challenge for clinical physicians. Herein, we report a 51-year-old female presenting with lower back pain and radiating pain at the left upper thigh. Magnetic resonance images of lumbar spine demonstrated an intradural cystic mass approximately 18 x 17 x 35 mm in size occupying L4 to L5, which appeared as the same signal intensity as CSF. At operation, a well encapsulated cystic mass was found. The pathological examination confirmed a diagnosis of schwannoma. The relevant literature was also reviewed. PMID- 21983383 TI - Textiloma as a complication of transsphenoidal surgery. AB - Transsphenoidal surgery is the mainstream in the management of sellar and anterior fossa diseases. However, textiloma, as known as cotton left behind during an operation, is rarely reported as a complication of transsphenoidal surgery. In this paper, we present a case of textiloma after transsphenoidal surgery. The patient had been suffering progressive blurred vision and she received transsphenoidal surgery for the diagnosis of pituitary tumor. However, the intermittent headaches persisted for half a year after the surgery. The subsequent images revealed a rim-like enhanced tumor in the sellar region. The retained cotton material was found when she underwent transcranial surgery. The etiology and management of textiloma are discussed, and the relevant literature also reviewed. PMID- 21983384 TI - Hemangioblastoma originating from the right cerebellopontine angle. AB - The morbidity of hemangioblastoma in the supratentorial region is very low, and is seldom found in the area of the cerebellopontine angle, so it is easily misdiagnosis before surgery. We report and discuss a case of hemangioblastoma originating at the right cerebellopontine angle in a 42-year-old female patient. PMID- 21983385 TI - Down syndrome presenting with multiple sclerosis, thyroid dysfunction, and diabetes mellitus. Multiple autoimmune disorders in a genetic disorder. AB - Down syndrome (DS) is one of the most common survivable chromosomal disorders, and is well known to be associated with multiple autoimmune diseases. Multiple sclerosis (MS) is a chronic inflammatory autoimmune demyelinating disease of the central nervous system. An association of DS and other autoimmune disease has been previously reported, and we report one case of DS in coexistence with MS, diabetes mellitus, and thyroid diseases. We suggest that MS, such as other autoimmune diseases, is prevalent in DS patients. PMID- 21983386 TI - Postoperative acute sialadenitis following posterior fossa surgery. PMID- 21983387 TI - Possible role of androgens in the pathophysiology of Tourette's syndrome. A hypothesis with clinical and therapeutic implications. PMID- 21983388 TI - Post stroke depression in acute stroke: correlating with site and stroke severity. PMID- 21983389 TI - Shift work is a source of stress among Military Police in Amazon, Brazil. PMID- 21983390 TI - How MRI can contribute to the diagnosis of acute demyelinating encephalomyelitis in children. PMID- 21983391 TI - Post varicella zoster virus myelitis in immunocompetent patients. PMID- 21983392 TI - A young adult with seizure and visual field defect. PMID- 21983393 TI - Lipidomics and imaging mass spectrometry. PMID- 21983395 TI - Work-related stress and intention to quit in newly graduated nurses. AB - Hospitals are fast paced health care environments that currently staff with Registered Nurse (RN) workforce comprised of more than 10% new graduate nurses. Past research has indicated that newly graduated nurses encounter stressful challenges transitioning from student (graduate) to the professional RN in the workforce. This issue must be given unabated priority, because loss of the new graduate has financial and patient safety implications. The purpose of this research study was to investigate work-related stress among recent nursing graduates and identify factors that influence their stress levels, as well as their intention to resign from their employment. Potential factors include gender, program type, work unit and duration, graduation time, and orientation. The study results indicate that junior RNs and BSN graduates are more likely to experience stress. Of all the stressors identified, equipment issues was the only factor that correlated both statistically and significantly to the participants' intention to quit. By investigating specific work-related stressors and coping strategies that these newly graduated nurses experience, this research may provide important information to better prepare and support future nursing students successfully transitioned to practice. PMID- 21983396 TI - Levels of phthalate metabolites in urine among mother-child-pairs - results from the Duisburg birth cohort study, Germany. AB - Phthalates are used ubiquitously and human exposure is widespread. Some phthalates are anti-androgens and have to be regarded as reproductive and developmental toxicants. In the Duisburg birth cohort study we examine the associations between hormonally active environmental agents and child development. Here we report the concentrations of 21 primary and secondary phthalate metabolites from seven low molecular weight (LMW) phthalates (DMP, DEP, BBzP, DiBP, DnBP, DCHP, DnPeP) and five high-molecular weight (HMW) phthalates (DEHP, DiNP, DiDP, DPHP, DnOP) in 208 urine samples from 104 mothers and their school-aged children. Analysis was performed by multidimensional liquid chromatography coupled to tandem mass spectrometry (LC/LC-MS/MS), using internal isotope-labeled standards. In both children and mothers, 18 out of 21 phthalate metabolites were detected above the limits of quantification (between 0.2 and 1.0 MUg/l) in nearly all urine samples. Among the LMW phthalates, the excretion level (geometric mean) of the SigmaDiBP metabolites was most prominent in children (103.9 MUg/l), followed by SigmaDnBP (56.5 MUg/l), and MEP (39.1 MUg/l). In mothers SigmaDiBP (66.6 MUg/l) was highest, followed by MEP (50.5 MUg/l), and SigmaDnBP (36.0 MUg/l). Among the HMW phthalates, SigmaDEHP was highest in children and mothers (55.7/28.9 MUg/l). Compared to reference values derived from the German Human Biomonitoring Commission, children's metabolite concentrations were within background levels, whereas for mothers considerably higher exposure to the LMW phthalates DnBP and DiBP, and the HMW phthalate DEHP was detected (MiBP: 10.7%; MnBP: 11.7%; SigmaDEHP: 23.3% of the samples were above the reference values). The LMW metabolites from DMP, DiBP, and DnBP, and the HMW metabolites from DEHP and DiNP were correlated between the mothers and children, probably indicating shared exposure in the immediate surrounding environment. Children showed higher excretion levels for most of the secondary metabolites than mothers, confirming previous findings on higher oxidized metabolite levels in children. The LMW metabolites SigmaDiBP, SigmaDnBP, and MMP, and the HMW metabolites SigmaDEHP were negatively associated with children's age. The LMW metabolites SigmaDiBP, SigmaDnBP, and MBzP were inversely associated with body mass index of the children. The LMW SigmaDiBP metabolites revealed a significant association with nicotine metabolites in urine from both children and mothers. Further analyses are ongoing to study long-term phthalate exposure and the associations with puberty outcome in these children. PMID- 21983397 TI - [Systemic autoimmune disorders and pregnancy]. AB - The coincidence of systemic autoimmune diseases and pregnancy may modify the outcome of the disease and the pregnancy due to the background immunologic and hormonal processes. The great majority of patients with autoimmune diseases are young females in their reproductive years, willing to have babies. Consequently, we have to prepare for this special situation. Our concept on childbearing in autoimmune women has changed within the last 30 years. Earlier, systemic lupus erythematosus flared in about 50% of patients during pregnancy, but the flare rate has significantly decreased recently. This improvement can be attributed to increased attention to low diseases activity at the time of conception, which might reduce to the half of the risk for flare. Tight control of patients and appropriate use of corticosteroids also contribute to the better results. The adequate use of anti-thrombotic agents resulted in a significant amelioration of pregnancy outcome in antiphospholipid syndrome. The earlier use of methotrexate and the introduction of tumor necrosis factor-alpha inhibitors in the treatment of rheumatoid arthritis have changed the natural characteristics of the disease. The increase in remission rate indirectly has beneficial effect on the number of planned and carried out pregnancies. Authors review the connection between systemic autoimmune disorders and pregnancy as well as the possibilities of medical treatment of such diseases during pregnancy. PMID- 21983394 TI - The influence of sex-linked genetic mechanisms on attention and impulsivity. AB - It is now generally agreed that there are inherent sex differences in healthy individuals across a number of neurobiological domains (including brain structure, neurochemistry, and cognition). Moreover, there is a burgeoning body of evidence highlighting sex differences within neuropsychiatric populations (in terms of the rates of incidence, clinical features/progression, neurobiology and pathology). Here, we consider the extent to which attention and impulsivity are sexually dimorphic in healthy populations and the extent to which sex might modulate the expression of disorders characterised by abnormalities in attention and/or impulsivity such as attention deficit hyperactivity disorder (ADHD), autism and addiction. We then discuss general genetic mechanisms that might underlie sex differences in attention and impulsivity before focussing on specific positional and functional candidate sex-linked genes that are likely to influence these cognitive processes. Identifying novel sex-modulated molecular targets should ultimately enable us to develop more effective therapies in disorders associated with attentional/impulsive dysfunction. PMID- 21983398 TI - [The uremic toxin, indoxyl sulfate, signifies cardio-renal risk and intestinal renal relationship]. AB - Uremic syndrome and condition is primarily a result of kidney failure in which uremic toxins are accumulated. More and more attention is paid to possibilities for removal of uremic toxins, which not only means dialysis, but also takes into account special dietary considerations and treatments, which aim to absorb the toxins or reduce their production. These uremic toxins, which also increase the cardiovascular risks, play a major part in morbidity and mortality of patients suffering from chronic renal failure and those receiving renal replacement therapy. One of them is a member of the indol group, the indoxyl sulfate. This toxin is difficult to remove with dialysis and is an endogenous protein-bound uremic toxin. Today we know that indoxyl sulfate is a vascular-nephrotoxic agent, which is able to enhance progression of cardiovascular and renal diseases. It is of particular importance that because of its redox potency, this toxin causes oxidative stress and antioxidant effects at the same time and, on top of that, it is formed in the intestinal system. Its serum concentration depends on the nutrition and the tubular function and, therefore, it can also signal the progression of chronic renal failure independently of glomerular filtration rate. Successful removal of indoxyl sulfate reduces the morbidity and mortality and improves survival. Therefore, it could be a possible target or area to facilitate the reduction of uremia in chronic renal failure. The use of probiotics and prebiotics with oral adsorbents may prove to be a promising opportunity to reduce indoxyl sulfate accumulation. PMID- 21983399 TI - [Outcome of differentiated thyroid cancer after initial treatment]. AB - Incidence of differentiated thyroid cancer has increased in the last two decades. This type of cancer is now being diagnosed at an earlier stage. Treatment strategy has been modified. AIMS: The goals of this study were to analyze the outcome of differentiated thyroid cancer after initial treatment (surgery and radioiodine ablation) in patients evaluated and followed up in a single centre between l999 and 2009, to compare these results with others as well as to monitor the adoption of international recommendation. 107 patients having T1-T2 differentiated thyroid cancer were studied. Mean follow-up time was 63 months. RESULTS: After surgery patients were prepared using thyroid hormone withdrawal or recombinant human thyrotropin, then 1.1-3.7 GBq 131-iodine was administered. First year evaluation consisted of ultrasound as well as serum thyrotropin and thyroglobulin (plus thyroglobulin antibody) determinations. Ablation success rate was 83% and the five year survival was 100%. There was not any cancer specific death. CONCLUSION: In the future somewhat more radical surgery and less remnant ablation is needed with unified follow-up protocol. PMID- 21983401 TI - [Percutaneous, endovascular treatment of innominate artery lesions is a safe and effective procedure]. AB - Percutaneous endovascular treatment (transluminar balloon angioplasty with or without stent implantation) of innominate artery lesions has become the treatment of choice prior to surgery in the past decades. Authors present the diagnostics, treatment and follow-up of two patients as examples from their largest series in the literature. A 74-year-old male patient with a history of hyperlipidemia, hypertension, nicotine abuse and lower limb claudication was admitted because of acute upper limb claudication and dizziness. Physical examination revealed blood pressure difference of 30 mmHg between his arms, and poststenotic flow pattern in the common carotid artery with retrograde flow in the vertebral artery on carotid duplex scan. Diagnostic angiography showed 80% stenosis of the innominate artery, which was treated with percutaneous transluminar balloon angioplasty with stent implantation. Follow-up examination at 5 months showed no significant restenosis or neurological complication. The second patient was a 59-year-old smoker female patient with hypertension and type 2 diabetes mellitus, who was evaluated for her upper limb claudication. Initial finding was the absence of radial pulse in the right side. Color duplex scan revealed proximal subocclusion, which was confirmed by angiography. In one stage, balloon angioplasty was made, with immediate pain relief. After 15 months the patient was symptom-free. These two cases demonstrate an excellent outcome of endovascular treatment of innominate artery lesions, as authors already reported in two retrospective studies. Balloon angioplasty with, or without stent deployment appears to be a safe procedure with excellent primary success rate. Review of international studies also indicates that endovascular therapy of the innominate artery is safe and effective. PMID- 21983400 TI - ["Does happiness help healing?" Immune response of hospitalized children may change during visits of the Smiling Hospital Foundation's Artists]. AB - Psychoneuroimmunologic studies on positive emotions are few, and their clinical relevance is limited. AIMS: This "SHoRT" (Smiling Hospital Research Team) study evaluates the effects that Smiling Hospital artists have on hospitalized children. METHODS: Blood samples were taken in a non-painful way through branules in an accredited Infectology Ward, 30 minutes before and 1 hour after a visit of tale tellers, puppeteers and handicraft artists. 24 children were visited and 9 were included in the control group. Blood lymphocyte counts and Th1/Th2 cytokine levels were determined. Artists evaluated their effect on a subjective scale. RESULTS: In the visited group, the increase of lymphocytes was 8.43% higher, the decrease was 12.45% lower, and the proportion of children showing increased lymphocyte counts was more increased. Changes were more marked after more successful visits. Authors found non-significant, still considerable changes in interferon-gamma level (p < 0.055) and in Th1/Th2 cytokine ratios. CONCLUSIONS: This pediatric study suggests that immunological changes may develop when more attention is given to hospitalized children. PMID- 21983403 TI - Influence of sludge retention time on tolerance of copper toxicity for polyphosphate accumulating organisms linked to polyhydroxyalkanoates metabolism and phosphate removal. AB - This study explored the influence of sludge retention time (SRT) on tolerance of copper invasion for polyphosphate accumulating organisms (PAOs) in an enhanced biological phosphorus removal (EBPR). The experimental data showed the anaerobic polyhydroxyalkanoates (PHA) storage for the sludge at 10d SRT was less influenced by copper invasion than those at 5d and 15d SRTs. The reaction of PAOs aerobically taking up phosphate for the sludge at 5d or 15d SRT almost ceased at 2 mg Cu L(-1), whereas PAOs in the sludge at 10d SRT retained half of the ability to take up phosphate. Both the PHAs degradation and synthesis rates decreased with increasing copper concentration, regardless of the SRTs. However, the copper inhibition of the former was greater than that of the later. PMID- 21983404 TI - Catalytic pyrolysis of tobacco rob: kinetic study and fuel gas produced. AB - The pyrolysis kinetics of tobacco rob (TR) was investigated using thermogravimetric analysis (TGA) under inert atmosphere, adding chemicals (dolomite and NiO) as catalysts by catalytic-mixing method. The TGA results showed that mass loss and mass loss rates were affected by catalysts. The conversion rates increased while the activation energy decreased. Moreover, the thermal decomposition behaviors of TR were studied in the fixed-bed reactor using dolomite and NiO/gamma-Al2O3 as catalysts by catalyst-bed method. A series of experiments had been performed to explore the effects of catalysts, and reaction temperature on the composition and yield of fuel gas. The experiments demonstrated that the catalysts had a high activity of cracking tar and hydrocarbons, as well as yielding a high fuel gas production. For both methods, dolomite and NiO revealed better catalytic performance as a view of enhancing conversion rates and increasing product gas yield. PMID- 21983405 TI - Use of silicone membranes to enhance gas transfer during microbial fuel cell operation on carbon monoxide. AB - Electricity generation in a microbial fuel cell (MFC) using carbon monoxide (CO) or synthesis gas (syngas) as a carbon source has been demonstrated recently. A major challenge associated with CO or syngas utilization is the mass transfer limitation of these sparingly soluble gases in the aqueous phase. This study evaluated the applicability of a dense polymer silicone membrane and thin wall silicone tubing for CO mass transfer in MFCs. Replacing the sparger used in our previous study with the membrane systems for CO delivery resulted in improved MFC performance and CO transformation efficiency. A power output and CO transformation efficiency of up to 18 mW LR(-1) (normalized to anode compartment volume) and 98%, respectively, was obtained. The use of membrane systems offers the advantage of improved mass transfer and reduced reactor volume, thus increasing the volumetric power output of MFCs operating on a gaseous substrate such as CO. PMID- 21983406 TI - Synthesis of fatty acid methyl ester from palm oil (Elaeis guineensis) with Ky(MgCa)2xO3 as heterogeneous catalyst. AB - Fatty acid methyl esters (FAME) were produced from palm oil using eggshell modified with magnesium and potassium nitrates to form a composite, low-cost heterogeneous catalyst for transesterification. The catalyst, prepared by the combination of impregnation/co-precipitation was calcined at 830 degrees C for 4 h. Transesterification was conducted at a constant temperature of 65 degrees C in a batch reactor. Design of experiment (DOE) was used to optimize the reaction parameters, and the conditions that gave highest yield of FAME (85.8%) was 5.35 wt.% catalyst loading at 4.5 h with 16:1 methanol/oil molar ratio. The results revealed that eggshell, a solid waste, can be utilized as low-cost catalyst after modification with magnesium and potassium nitrates for biodiesel production. PMID- 21983407 TI - Comparative study of pyrolysis of algal biomass from natural lake blooms with lignocellulosic biomass. AB - Pyrolysis experiments were performed with algal and lignocellulosic feedstocks under similar reactor conditions for comparison of product (bio-oil, gas and bio char) yields and composition. In spite of major differences in component bio polymers, feedstock properties relevant to thermo-chemical conversions, such as overall C, H and O-content, C/O and H/C molar ratio as well as calorific values, were found to be similar for algae and lignocellulosic material. Bio-oil yields from algae and some lignocellulosic materials were similar; however, algal bio oils were compositionally different and contained several N-compounds (most likely from protein degradation). Algal bio-char also had a significantly higher N-content. Overall, our results suggest that it is feasible to convert algal cultures deficient in lipids, such as nuisance algae obtained from natural blooms, into liquid fuels by thermochemical methods. As such, pyrolysis technologies being developed for lignocellulosic biomass may be directly applicable to algal feedstocks as well. PMID- 21983408 TI - Anaerobic digestion challenge of raw olive mill wastewater. AB - Olive mill wastewater (OMW) was digested in its original composition (100% v/v) in an anaerobic hybrid. High concentrations (54-55 kg COD m(-3)), acid pH (5.0) and lack of alkalinity and nitrogen are some OMW adverse characteristics. Loads of 8 kg COD m(-3) d(-1) provided 3.7-3.8 m3 biogas m(-3) d(-1) (63-64% CH4) and 81-82% COD removal. An effluent with basic pH (8.1) and high alkalinity was obtained. A good performance was also observed with weekly load shocks (2.7-4.1, 8.4-10.4 kg COD m(-3) d(-1)) by introducing piggery effluent and OMW alternately. Biogas of 3.0-3.4 m3 m(-3) d(-1) (63-69% CH4) was reached. Developed biomass (350 days) was neither affected by raw OMW nor by organic shocks. Through the effluents complementarity concept, a stable process able of degrading the original OMW alone was obtained. Unlike what is referred, OMW is an energy resource through anaerobiosis without additional expenses to correct it or decrease its concentration/toxicity. PMID- 21983409 TI - Electricity generation and microbial community changes in microbial fuel cells packed with different anodic materials. AB - Four materials, carbon felt cube (CFC), granular graphite (GG), granular activated carbon (GAC) and granular semicoke (GS) were tested as packed anodic materials to seek a potentially practical material for microbial fuel cells (MFCs). The microbial community and its correlation with the electricity generation performance of MFCs were explored. The maximum power density was found in GAC, followed by CFC, GG and GS. In GAC and CFC packed MFCs, Geobacter was the dominating genus, while Azospira was the most populous group in GG. Results further indicated that GAC was the most favorable for Geobacter adherence and growth, and the maximum power densities had positive correlation with the total biomass and the relative abundance of Geobacter, but without apparent correlation with the microbial diversity. Due to the low content of Geobacter in GS, power generated in this system may be attributed to other microorganisms such as Synergistes, Bacteroidetes and Castellaniella. PMID- 21983410 TI - Ethanol production from wheat straw by recombinant Escherichia coli strain FBR5 at high solid loading. AB - Ethanol production by a recombinant bacterium from wheat straw (WS) at high solid loading by separate hydrolysis and fermentation (SHF) and simultaneous saccharification and fermentation (SSF) was studied. The yield of total sugars from dilute acid pretreated WS (150 g/L) after enzymatic saccharification was 86.3+/-1.5 g/L. The pretreated WS was bio-abated by growing a fungal strain aerobically in the liquid portion for 16 h. The recombinant Escherichia coli strain FBR5 produced 41.1+/-1.1 gethanol/L from non-abated WS hydrolyzate (total sugars, 86.6+/-0.3 g/L) in 168 h at pH7.0 and 35 degrees C. The bacterium produced 41.8+/-0.0 g ethanol/L in 120 h from the bioabated WS by SHF. It produced 41.6+/-0.7 g ethanol/L in 120 h from bioabated WS by fed-batch SSF. This is the first report of the production of above 4% ethanol from a lignocellulosic hydrolyzate by the recombinant bacterium. PMID- 21983411 TI - Protozoan predation on nitrification performance and microbial community during bioaugmentation. AB - The effects of predation on nitrification performance and microbial community during bioaugmentation were investigated. Although most of the nitrification ability of the seed source was lost in the seeded reactors, bioaugmentation significantly enhanced the activity and community of the nitrifiers. The ammonium uptake rate (AUR) increased from 2.59 to 15.25 mg NH4+-N/Lh and 2.88 to 13.36 mg NH4+-N/Lh, and the nitrite uptake rate (NUR) increased from 0.80 to 4.02 mg NO2- N/Lh and 0.76 to 4.34 mg NO2--N/Lh for the reactors with and without protozoa inhibition, respectively. The population of nitrifiers increased, and the dominant nitrite oxidizing bacteria (NOB) transferred from Nitrospira to Nitrobacter. Predation had an evident influence on the microbial community of nitrifiers, especially the K-strategist, which was more vulnerable to predation than r-strategist during bioaugmentation due to its low growth rate. However, predation did not have a significant effect on the nitrification performance. PMID- 21983412 TI - Antibiotics-free stable polyhydroxyalkanoate (PHA) production from carbon dioxide by recombinant cyanobacteria. AB - A practical antibiotics-free plasmid expression system in cyanobacteria was developed by using the complementation of cyanobacterial recA null mutation with the EscherichiacolirecA gene on the plasmid. This system was applied to the production of polyhydroxyalkanoate (PHA), a biodegradable plastic, and the transgenic cyanobacteria stably maintained the pha genes for PHA production in the antibiotics-free medium, and accumulated up to 52% cell dry weight of PHA. PMID- 21983413 TI - Treatment of fish processing wastewater with microalgae-containing microbiota. AB - Two photobioreactors inoculated with microalgae from a lagoon containing aerobically treated swine slurry and with sludge from a membrane submerged bioreactor treating winery wastewater were established to treat fish processing wastewater (FPW) at 23 and 31 degrees C, respectively. The hydraulic retention time (HRT) was decreased in the photobioreactors from 10 to 5 days. Ammonium was completely exhausted in both photobioreactors; however, volatilization was the main removal mechanism for the highest applied load whereas biomass assimilation was the main mechanism for the lowest applied load. Approximately 70% of TCOD (total chemical oxygen demand) and phosphate removal was achieved regardless of temperature. Biomass productivity was as much as 55% higher at 31 degrees C than at 23 degrees C. These results suggested that fish processing wastewater could be effectively treated using this technology. PMID- 21983414 TI - Effect of inhibitors formed during wheat straw pretreatment on ethanol fermentation by Pichia stipitis. AB - The inhibitory effect of the main inhibitors (acetic acid, furfural and 5 hydroxymethylfurfural) formed during steam explosion of wheat straw was studied through ethanol fermentations of model substrates and hydrolysates from wheat straw by Pichia stipitis. Experimental results showed that an increase in acetic acid concentration led to a reduction in ethanol productivity and complete inhibition was observed at 3.5 g/L. Furfural produced a delay on sugar consumption rates with increasing concentration and HMF did not exert a significant effect. Fermentations of the whole slurry from steam exploded wheat straw were completely inhibited by a synergistic effect due to the presence of 1.5 g/L acetic acid, 0.15 g/L furfural and 0.05 g/L HMF together with solid fraction. When using only the solid fraction from steam explosion, hydrolysates presented 0.5 g/L of acetic acid, whose fermentations have submitted promising results, providing an ethanol yield of 0.45 g ethanol/g sugars and the final ethanol concentration reached was 12.2 g/L (10.9 g ethanol/100 g DM). PMID- 21983415 TI - Fraud in biomedical research - the role of journal Editors. PMID- 21983416 TI - The effects of hippocampal opioidergic and septal GABAergic system interactions on anxiety-like behavior in rats. AB - AIMS: Previous studies have shown that the septum and hippocampus are connected and play a key role in anxiety-related behavior. In the present study, the effects of the interactions between the opioidergic system in the dorsal hippocampus (CA1) and the GABAergic system in the medial septum on anxiety in male Wistar rats were investigated. MAIN METHODS: An elevated plus maze was used to study the effects of anxiogenic and anxiolytic drugs in rodents. Male Wistar rats were used for this test. We injected morphine (2.5, 5.0, and 7.5 MUg/rat) into the CA1 and GABA(A) agonist muscimol (2.5, 5.0, and 10.0 ng/rat) into the intra-medial septum (MS). Conversely, we detected the microinjection of bicuculline, a GABA(A) antagonist (10, 20, and 30 ng/rat), into the MS. OAT%, OAE% and locomotor activity were determined by this behavioral test. KEY FINDINGS: We found that the simultaneous administration of intra-CA1 morphine (2.5 MUg/rat) and intra-MS muscimol (2.5 ng/rat) increased the magnitude of anxiolysis. On the other hand, simultaneous administration of intra-CA1 morphine (7.5 MUg/rat) and intra-MS bicuculline decreased the anxiolytic effect. SIGNIFICANCE: In conclusion, our data suggest that the opioidergic system in the CA1 is involved in anxiety-related behavior and influences the GABAergic system within the MS. In addition, we observed that the interactions between the opioidergic and GABAergic systems within the septohippocampus increased anxiety related behavior compared to stimulation of these receptor systems independently. PMID- 21983417 TI - Fraud in biomedical research--the role of journal editors. PMID- 21983418 TI - Protective effects of intraperitoneal injection of TAT-SOD against focal cerebral ischemia/reperfusion injury in rats. AB - AIMS: The intracellular superoxide anion has been shown to be involved in brain injury. TAT-Superoxide dismutase (TAT-SOD) can be transduced across the cell membrane to scavenge superoxide. This protein's unique properties make it a promising therapeutic candidate to attenuate cerebral damage. In this study, we sought further the understanding of the fusion protein's cerebral protective effects and the mechanism which is exerted in these effects. MAIN METHODS: Male Sprague Dawley rats (n=100, 230+/-20 g) were divided randomly into five experimental groups: a sham group, a cerebral Ischemia/Reperfusion (I/R) group treated with saline (20 ml/Kg, i.p.), and three cerebral I/R groups treated with TAT-SOD (25 KU/ml/Kg, i.p.) at either 2h before I/R, 2h after I/R or 4h after I/R. Cerebral I/R injury was facilitated by inducing ischemia for two hours followed by 24h reperfusion. The levels of SOD, Malondialdehyde (MDA), and ATPase in cerebral tissues were determined. The apoptotic indexes were evaluated, and apoptosis genes were analyzed immunohistochemically. KEY FINDINGS: TAT-SOD treatment significantly increased cerebral SOD and ATPase activities, decreased MDA content, and remarkably reduced apoptosis indexes. TAT-SOD treatments 2h before or after I/R significantly reduced caspase-3 and bax proteins and boosted bcl-2 protein, while the treatment at 4h after I/R showed no influence on the three proteins. SIGNIFICANCE: TAT-SOD treatment effectively enhanced cerebral antioxidant ability, reduced lipid peroxidation, preserved mitochondrial ATPase and thus inhibited nerve cell apoptosis. The effective treatment window extended from 2h before to 2h after I/R. PMID- 21983419 TI - Morphofunctional interactions between galanin and GnRH-containing neurones in the diencephalon of the ewe. The effect of oestradiol. AB - In rodents, the neuropeptide galanin (Gal) is involved in controlling the release of gonadotrophin-releasing hormone (GnRH). In the female, this peptide is colocalized in a subpopulation of GnRH neurones and its expression is stimulated by oestradiol. In the ewe, the morphofunctional relationship between these two neuronal peptides is poorly understood. The morphological interaction between Gal and GnRH was studied in ewes treated with oestradiol or with colchicine and in control animals. Five ewes were treated for 6h with oestradiol implants, a treatment known to induce a preovulatory surge of GnRH, and compared with five control animals. In addition, four animals received an intracerebroventricular injection of colchicine known to increase the intracellular level of galanin immunoreactivity. The morphological relationship between the two peptides was investigated by immunofluorescence using specific antibodies on the same sections, and the results were analysed using confocal microscopy. In colchicine treated ewes, numerous Gal-immunoreactive neurones were found in the preoptic area in the vicinity of GnRH-immunoreactive neurones, but the two peptides were never observed in the same neurone. In all animals, Gal-ir fibres were observed to be in apposition to GnRH-containing perikarya in the preoptic area and these appositions were more numerous in oestradiol-treated ewes than in control animals. In contrast with rodents, galanin was not colocalized with GnRH in the neurones of the preoptic area of ewes, but this peptide could control GnRH neuronal secretion through axosomatic interactions. However, the presence of synaptic contacts between galanin terminals and GnRH perikarya needs to be confirmed by electron microscopy. As in rodents and primates, galanin could mediate the positive feedback of oestradiol on GnRH neurones during the preovulatory surge in ewes. PMID- 21983420 TI - Transcription and translation in a package deal: the TISU paradigm. AB - The major strategy for cap dependent translation involves ribosomal scanning. In the scanning mechanism the small ribosomal subunit is recruited to the mRNA through the m7G cap and then scans the 5' UTR until it reaches an AUG codon. This short review focuses on a recently discovered alternative strategy of cap dependent translation that operates without scanning, but nonetheless is highly efficient and accurate. This non-scanning translation is directed by the Translation Initiator of Short 5' UTR (TISU) element. TISU is strictly located close to the 5' end of the mRNA, resulting in a very short 5' UTR. It is present in a sizable number of mammalian genes, many of them with fundamental cellular functions. In addition to its unique translational activity, TISU is also a transcription regulatory element that is specifically enriched in TATA-less promoters. Thus TISU represents a prototype regulatory element that links mammalian transcription to a specific mode of translation initiation. PMID- 21983421 TI - Expressed sequence tags (ESTs) based identification of genes and expression analysis of leukocyte cell-derived chemotaxin-2 (LECT2) from Epinephelus bruneus. AB - The kelp grouper, Epinephelus bruneus, is an economically important intensively cultured species in Southeast Asia. Despite the insatiable demand its large-scale production has been hindered by problems associated with water quality, nutrition, and diseases especially due to increased rearing density. It is generally accepted that in fish both innate and adaptive immune system provide protection from diseases. In the present study a cDNA library of Streptococcus iniae-challenged kelp grouper was constructed to identify the genes that reveal molecular mechanism, physiological functions, and gene expression in different tissues using expressed sequence tags (ESTs) and RT-PCR strategy. Of a total of 2170 ESTs examined 279 (12.9%) were identified as contig and 860 (39.6%) as singletons. A total of 190 important immune and enzyme related genes (16.7%) were identified in both contig and singletons. The key immune molecules identified comprise complement factors, chemotaxin, chemokine, Fas ligand, ferritins, hepcidin, lysozyme c, MHC, and TLR which are involved in the innate or adaptive immune system. Among the genes a full-length cDNA of leukocyte cell-derived chemotaxin-2 (EbLECT2) with 540 base pair (bp) was identified; it consists of a 5'-untranslated region (UTR) of 17 bp, a 3'-UTR of 76 bp, and a stop codon TAA in 3'-UTR. The EbLECT2 is an important molecule in the innate immunity. It is a multifunctional protein involved in cell growth, differentiation, and autoimmunity. The open reading frame (ORF) of the EbLECT2 encodes with 155 amino acid (aa) residues with a predicted molecular weight and isoelectric point (pI) of 17 kDa and 9, respectively. The close phylogenetic relationship of EbLECT2 shares the highest similarity with the already reported LECT2 from Epinephelus coioides (96%) and Epinephelus akaara (94%). EbLECT2 mRNA was expressed predominantly in liver, spleen, and kidney while the expression was moderate in gills, heart, and muscle in E. bruneus after being challenged with LPS from Escherichia coli and pathogenic bacterium Vibrio anguillarum both of which involve the immune defense system. Further, the recombinant mature EbLECT2 (rEbLECT2) was successfully expressed in E. coli BL21 (DE3), and the antiserum against EbLECT2 was obtained for further investigations. The significant number of ESTs genome results obtained constitutes a powerful resource for further investigation to establish the gene discovery, functional genomic research, molecular mechanisms, and development of microarrays for the gene expression studies in kelp grouper. PMID- 21983422 TI - Primary malignant fibrous histiocytoma (myxofibrosarcoma/pleomorphic sarcoma not otherwise specified) of the breast: clinicopathologic study of 19 cases. AB - We present 19 cases of primary breast malignant fibrous histiocytoma (MFH) or myxofibrosarcoma/pleomorphic sarcoma not otherwise specified, the largest series to date, and compare our results with those in the literature to better define MFH in this anatomical location. Twenty-seven cases (MFH, myxofibrosarcoma, or pleomorphic sarcoma not otherwise specified) were reviewed using World Health Organization and French Federation of Cancer Centers criteria. Inclusion required location within breast parenchyma without extensive chest wall involvement. Morphological features were recorded, and immunohistochemistry was applied. Clinical data were extracted from patients' medical records. Clinically, there was 1 male patient. Of 15 patients with follow-up, 5 (33% overall) died of disease within an average of 7 months after diagnosis. Distant metastases and older patient age were associated with poor survival. Storiform-pleomorphic subtype was most common (10/19) with myxofibrosarcoma (6/19) and giant cell subtype (1/19) also observed. Unique lymphocyte-rich (1/19) and pleomorphic hyalinizing angiectatic tumor-like (1/19) morphologies are presented. Immunohistochemistry demonstrated expression of CD68 (71%), focal smooth muscle actin (36%), with rare focal estrogen and progesterone receptor immunoreactivity. All cases were negative for CD34, S-100 protein, desmin 33, and keratins, including CK7, CK20, CK5/6, and CK18. Malignant fibrous histiocytoma occurs as a primary lesion in breast parenchyma. Attention to morphological detail and immunohistochemistry avoids misdiagnosis. Entrapped breast ductal epithelium should not be misinterpreted as the epithelial component of a biphasic tumor. A florid lymphoid response should not be confused with metaplastic carcinoma. Pleomorphic hyalinizing angiectatic tumor-like features may be observed in MFH. Our study confirms the presence of MFH in breast and presents unique morphological observations of primary breast MFH. PMID- 21983423 TI - Expression of vitellogenin in the testis and kidney of the spotted ray Torpedo marmorata exposed to 17beta-estradiol. AB - In vertebrates, the liver was long thought to be the only site of vitellogenin (Vtg) production, but recent studies demonstrated that Vtg is also expressed in extrahepatic districts. The aim of this paper is to assess, by in situ hybridization and immunohistochemistry, the expression of Vtg in the testis and kidney of Torpedo marmorata exposed to 17beta-estradiol (E(2)). In treated samples vtg mRNA and Vtg were detected contemporaneously only in the testis; differently the kidney cells were positive to Vtg antibody, but negative to vtg mRNA. This is the first study to assess that male germ cells, after an exposure to E(2), synthesize Vtg in a stage-dependent manner. The presence of Vtg and the modifications observed in the kidney after E(2) treatment are discussed. PMID- 21983424 TI - Curious eyes: individual differences in personality predict eye movement behavior in scene-viewing. AB - Visual exploration is driven by two main factors - the stimuli in our environment, and our own individual interests and intentions. Research investigating these two aspects of attentional guidance has focused almost exclusively on factors common across individuals. The present study took a different tack, and examined the role played by individual differences in personality. Our findings reveal that trait curiosity is a robust and reliable predictor of an individual's eye movement behavior in scene-viewing. These findings demonstrate that who a person is relates to how they move their eyes. PMID- 21983425 TI - Influence of alfalfa grazing-based feeding systems on carcass fat colour and meat quality of light lambs. AB - One hundred and twenty-seven lambs were fed as follows: lambs and dams grazing alfalfa (Gr); the same as Gr but lambs had access to concentrate (Gr + S); ewes grazed and lambs received milk and concentrate until weaning and thereafter concentrate and straw (Rat-Gr); ewes and lambs were stall-fed (Ind). Lambs were slaughtered at 22-24 kg live weight and fat and M. rectus abdominis colour was measured instrumentally and subjectively. The evolution of the instrumental colour and texture of M. longissimus lumborum was also recorded. There were significant differences in the instrumental colour of subcutaneous fat amongst feeding systems, but no differences were observed upon visual appraisal. On average, M. rectus abdominis colour in the four feeding systems was classed as pink. Differences in longissimus thoracis colour at 0 h disappeared at 24h of air exposure and there were no differences in pH or cooking losses. At no time were any differences in instrumental texture found. PMID- 21983426 TI - The volatile compounds in lamb fat are affected by the time of grazing. AB - This study was designed to assess whether different grazing managements affect the appearance of organic volatile compounds (VOC) in lamb fat. Forty-two lambs were divided into four groups: 9 lambs were restricted in stall and fed concentrate (S group); 12 lambs grazed from 9 am to 5 pm (8h group); 10 lambs grazed from 9 am to 1 pm (4 hAM group) and 11 lambs grazed from 1 pm to 5 pm (4 hPM group). After 72 days on feed the animals were slaughtered and the perirenal fat subjected to SPME-GC/MS analysis of VOC; the data were analyzed by stepwise discriminant analysis. The 6-methyl-2-heptanone and furanone, 2,5-dimethyl, 4 hydroxy-3(2H) allowed discrimination between the 4 hAM and the 4 hPM animals. These are the first results indicating that the time of the day in which the animals are allowed to graze affects the appearance of VOC in lamb fat. PMID- 21983427 TI - Chronic subhepatotoxic exposure to arsenic enhances hepatic injury caused by high fat diet in mice. AB - Arsenic is a ubiquitous contaminant in drinking water. Whereas arsenic can be directly hepatotoxic, the concentrations/doses required are generally higher than present in the US water supply. However, physiological/biochemical changes that are alone pathologically inert can enhance the hepatotoxic response to a subsequent stimulus. Such a '2-hit' paradigm is best exemplified in chronic fatty liver diseases. Here, the hypothesis that low arsenic exposure sensitizes liver to hepatotoxicity in a mouse model of non-alcoholic fatty liver disease was tested. Accordingly, male C57Bl/6J mice were exposed to low fat diet (LFD; 13% calories as fat) or high fat diet (HFD; 42% calories as fat) and tap water or arsenic (4.9 ppm as sodium arsenite) for ten weeks. Biochemical and histologic indices of liver damage were determined. High fat diet (+/- arsenic) significantly increased body weight gain in mice compared with low-fat controls. HFD significantly increased liver to body weight ratios; this variable was unaffected by arsenic exposure. HFD caused steatohepatitis, as indicated by histological assessment and by increases in plasma ALT and AST. Although arsenic exposure had no effect on indices of liver damage in LFD-fed animals, it significantly increased the liver damage caused by HFD. This effect of arsenic correlated with enhanced inflammation and fibrin extracellular matrix (ECM) deposition. These data indicate that subhepatotoxic arsenic exposure enhances the toxicity of HFD. These results also suggest that arsenic exposure might be a risk factor for the development of fatty liver disease in human populations. PMID- 21983429 TI - A systematic review of 'knowledge of dementia' outcome measures. AB - Knowledge of dementia measures are key to identifying areas of misinformation and establishing knowledge levels, thus guiding educational programmes and interventions. A three-step literature search was undertaken to identify measures of knowledge in dementia. An evaluation framework was employed articulating quality indicators for the psychometric properties of measures, based on their development and use within research studies. Five measures were identified: the Alzheimer's Disease Knowledge Test (ADKT, Dieckmann et al., 1988); the University of Alabama Alzheimer's Disease Knowledge Test for Health Professionals (UAB-ADKT, Barrett et al., 1997); the Dementia Quiz (DQ, Gilleard and Groom, 1994); the Knowledge of Aging and Memory Loss and Care (KAML-C, Kuhn et al., 2005) and the Alzheimer's Disease Knowledge Scale (ADKS, Carpenter et al., 2009). All measures followed a standard scale development process, generally with acceptable reliability and validity. Many studies used measures on populations beyond the target sample, without re-establishing the psychometric properties of the scales. There are limitations with all the measures, including weaknesses in psychometric properties, being outdated and having limited scope. Although the ADKT was once suited to international use and has established psychometric properties, some items are now outdated. The ADKS positions itself as an updated version of the ADKT, yet has not been used beyond the original development study. The DQ is most the suitable for family carers. All measures require periodic updates, to keep pace with the expanding field of dementia. More robust, contemporary measures of knowledge are required. PMID- 21983428 TI - Differential state-dependent modification of rat Na(v)1.6 sodium channels expressed in human embryonic kidney (HEK293) cells by the pyrethroid insecticides tefluthrin and deltamethrin. AB - We expressed rat Na(v)1.6 sodium channels in combination with the rat beta1 and beta2 auxiliary subunits in human embryonic kidney (HEK293) cells and evaluated the effects of the pyrethroid insecticides tefluthrin and deltamethrin on expressed sodium currents using the whole-cell patch clamp technique. Both pyrethroids produced concentration-dependent, resting modification of Na(v)1.6 channels, prolonging the kinetics of channel inactivation and deactivation to produce persistent "late" currents during depolarization and tail currents following repolarization. Both pyrethroids also produced concentration dependent hyperpolarizing shifts in the voltage dependence of channel activation and steady state inactivation. Maximal shifts in activation, determined from the voltage dependence of the pyrethroid-induced late and tail currents, were ~25mV for tefluthrin and ~20mV for deltamethrin. The highest attainable concentrations of these compounds also caused shifts of ~5-10mV in the voltage dependence of steady state inactivation. In addition to their effects on the voltage dependence of inactivation, both compounds caused concentration-dependent increases in the fraction of sodium current that was resistant to inactivation following strong depolarizing prepulses. We assessed the use-dependent effects of tefluthrin and deltamethrin on Na(v)1.6 channels by determining the effect of trains of 1 to 100 5-ms depolarizing prepulses at frequencies of 20 or 66.7Hz on the extent of channel modification. Repetitive depolarization at either frequency increased modification by deltamethrin by ~2.3-fold but had no effect on modification by tefluthrin. Tefluthrin and deltamethrin were equally potent as modifiers of Na(v)1.6 channels in HEK293 cells using the conditions producing maximal modification as the basis for comparison. These findings show that the actions of tefluthrin and deltamethrin of Na(v)1.6 channels in HEK293 cells differ from the effects of these compounds on Na(v)1.6 channels in Xenopus oocytes and more closely reflect the actions of pyrethroids on channels in their native neuronal environment. PMID- 21983430 TI - Improvement of the Cramer classification for oral exposure using the database TTC RepDose--a strategy description. AB - The present report describes a strategy to refine the current Cramer classification of the TTC concept using a broad database (DB) termed TTC RepDose. Cramer classes 1-3 overlap to some extent, indicating a need for a better separation of structural classes likely to be toxic, moderately toxic or of low toxicity. Groups of structurally similar compounds of high toxicity in Cramer class 1 and of moderate to low toxicity in Cramer class 3 were identified and reassigned to the appropriate Cramer class according to their observed toxicological potency in in vivo studies. This refinement results in a better discrimination of Cramer classes 1 and 3 and an increased number of substances in Cramer class 2. The TTC values are 8.7 MUmol/person/d (class 1), 6.72 MUmol/person/d (class 2) and 0.28 MUmol/person/d (class 3). Assuming a median molecular weight of 220 g/mol for the compounds of the TTC RepDose DB, the corresponding TTC values are 1930, 1478 and 63 MUg/person/d for classes 1, 2 and 3 respectively. The derived thresholds are close to the TTC values initially proposed by Munro with 1800, 540 and 90 MUg/person/d for classes 1, 2 and 3 respectively. Additional structural classes are discussed with a view to further refinement of the current Cramer classification scheme. PMID- 21983431 TI - First-principles study of ZnO cluster-decorated carbon nanotubes. AB - We have investigated the structural, electronic and carbon monoxide (CO) detection properties of the ZnO cluster-decorated single-walled carbon nanotubes (SWCNTs) by using density functional theory (DFT). The stable structures of hybrid ZnO/SWCNT materials are that the ZnO cluster plane is perpendicular to the surface of SWCNTs with the Zn atoms towards the SWCNTs (Zn atom above axial C-C bond or above the C atom). For the ZnO cluster-decorated semiconducting SWCNTs, the SWCNTs present p-type characteristics which may lead to the decrease of conductance upon illumination with ultraviolet (UV) light. The CO can be adsorbed on the hybrid ZnO/SWCNT materials due to the charge transfer between them. Compared with isolated ZnO clusters or bare SWCNTs, the ZnO/SWCNT network would have excellent CO detection ability due to their suitable adsorption energy and conductivity. PMID- 21983432 TI - Organizational factors associated with decreased mortality among Veterans Affairs patients with an ICU stay. AB - In-hospital mortality rates associated with an ICU stay are high and vary widely among units. This variation may be related to organizational factors such as staffing patterns, ICU structure, and care processes. We aimed to identify organizational factors associated with variation in in-hospital mortality for patients with an ICU stay. This was a retrospective observational cross-sectional study using administrative data from 34 093 patients from 171 ICUs in 119 Veterans Health Administration hospitals. Staffing and patient data came from Veterans Health Administration national databases. ICU characteristics came from a survey in 2004 of ICUs within the Veterans Health Administration. We conducted multilevel multivariable estimation with patient-, unit-, and hospital-level data. The primary outcome was in-hospital mortality. Of 34 093 patients, 2141 (6.3%)died in the hospital. At the patient level, risk of complications and having a medical diagnosis were significantly associated with a higher risk of mortality. At the unit level, having an interface with the electronic medical record was significantly associated with a lower risk of mortality. The finding that electronic medical records integrated with ICU information systems are associated with lower in-hospital mortality adds support to existing evidence on organizational characteristics associated with in-hospital mortality among ICU patients. PMID- 21983433 TI - Quality assurance of nursing web sites: development and implications of the ALEU method. AB - This article presents a study that evaluated the physical accessibility, readability, and usability of Spanish nursing Web sites and discusses the quality assurance issues raised, which are relevant to the wider nursing community. The Internet is recognized as an important source of health information for both nurses and the general public. Although it makes health-related information universally available, the wide variation in the overall quality of health Web sites is problematic. This raises many questions for the nursing profession: about what constitutes a good-quality Web site, about the nature of the information that nurses are finding and using to support their professional education, research, and clinical practice, and about the impact that Internet information ultimately has on health interactions and nursing care. The process of completing this small study showed that it is possible to usefully assess dimensions of Web site quality and suggested that it may be feasible to develop tools to help nurses evaluate national and international nursing Web sites. More research is needed to understand how nurses use the Internet to support their everyday professional practices, but the development and application of international Web site quality assurance tools may be important for maintaining professional nursing standards in the Internet age. PMID- 21983434 TI - Glutaredoxin 2 knockout increases sensitivity to oxidative stress in mouse lens epithelial cells. AB - Glutaredoxin belongs to the oxidoreductase family, with cytosolic glutaredoxin 1 (Grx1) and mitochondrial glutaredoxin 2 (Grx2) isoforms. Of the two isozymes, the function of Grx2 is not well understood. This paper describes the effects of Grx2 deletion on cellular function using primary lens epithelial cell cultures isolated from Grx2 gene knockout (KO) and wild-type (WT) mice. We found that both cell types showed similar growth patterns and morphology and comparable mitochondrial glutathione pool and complex I activity. Cells with deleted Grx2 did not show affected Grx1 or thioredoxin expression but exhibited high sensitivity to oxidative stress. Under treatment with H(2)O(2), the KO cells showed less viability, higher membrane leakage, enhanced ATP loss and complex I inactivation, and weakened ability to detoxify H(2)O(2) in comparison with the WT cells. The KO cells had higher glutathionylation in the mitochondrial proteins, particularly the 75-kDa subunit of complex I. Recombinant Grx2 deglutathionylated complex I and restored most of its activity. We conclude that Grx2 has a function that protects cells against H(2)O(2)-induced injury via its peroxidase and dethiolase activities; particularly, Grx2 prevents complex I inactivation and preserves mitochondrial function. PMID- 21983435 TI - Identification of oxidized phospholipids by electrospray ionization mass spectrometry and LC-MS using a QQLIT instrument. AB - Phospholipids are complex and varied biomolecules that are susceptible to lipid peroxidation after attack by free radicals or electrophilic oxidants and can yield a large number of different oxidation products. There are many available methods for detecting phospholipid oxidation products, but also various limitations and problems. Electrospray ionization mass spectrometry allows the simultaneous but specific analysis of multiple species with good sensitivity and has a further advantage that it can be coupled to liquid chromatography for separation of oxidation products. Here, we explain the principles of oxidized phospholipid analysis by electrospray mass spectrometry and describe fragmentation routines for surveying the structural properties of the analytes, in particular precursor ion and neutral loss scanning. These allow targeted detection of phospholipid headgroups and identification of phospholipids containing hydroperoxides and chlorine, as well as the detection of some individual oxidation products by their specific fragmentation patterns. We describe instrument protocols for carrying out these survey routines on a QTrap5500 mass spectrometer and also for interfacing with reverse-phase liquid chromatography. The article highlights critical aspects of the analysis as well as some limitations of the methodology. PMID- 21983436 TI - Rewiring the brain with repeated retrieval: a parametric fMRI study of the testing effect. AB - The "testing effect" refers to the beneficial effects on memory performance from being tested, a phenomenon of potentially substantial implications in educational settings. While the effect itself is firmly established in previous research, little is known of related brain changes. Here we used fMRI and a parametric design to show that repeated successful retrieval during a memory acquisition phase leads to higher brain activity in the anterior cingulate cortex (ACC) at a subsequent test phase. The extent of ACC activity increase correlated across individuals with memory performance 5 months later. In relation to recent research that associates the ACC with memory consolidation processes, the present results suggest that the testing effect may operate at the systems level by enhancing consolidation of memory representations. PMID- 21983437 TI - Synthesis and acrosin inhibitory activity of substituted 4-amino-N (diaminomethylene) benzenesulfonamide derivatives. AB - A series of new substituted 4-amino-N-(diaminomethylene) benzenesulfonamides were synthesized and their in vitro acrosin inhibitory activities were evaluated. Most of the compounds showed potent acrosin inhibitory activities with compounds 4o and 4p being significantly more potent than the control compound N-alpha-tosyl-L lysyl-chloromethyl-ketone (TLCK). The compounds provide a new scaffold for the development of acrosin inhibitory agents. PMID- 21983438 TI - Structure-activity relationship study of arylsulfonylimidazolidinones as anticancer agents. AB - In an effort to find novel N-arylsulfonylimidazolidinones as highly potent anticancer agent, the structure-activity relationship of ethyl 2-methyl-4-(2-oxo 4-phenylimidazolidin-1-ylsulfonyl)phenylcarbamate was explored through synthesis and evaluation of in vitro cytotoxicity of its analogs against HCT116, A549 and NCL-H460 cancer cell lines. Among the synthesized derivatives, the carbamate analogs (4a-f and 4k-p) exhibited superior cytotoxicity to doxorubicin for all cancer cell lines. The SAR studies of these derivatives confirm that the intact 4 phenyl-l-benzenesulfonylimidazolidinone has a pivotal role as a basic pharmacophore and hydrophobic substitutions only at 2-position of 1 aminobenzenesulfonyl moiety are beneficial for the enhancement of the activity. PMID- 21983439 TI - Design, synthesis, and SAR studies of novel polycyclic acids as potent and selective inhibitors of human 11beta-hydroxysteroid dehydrogenase type 1 (11beta HSD-1). AB - Starting from high throughput screening hit 2-adamantyl acetic acid 3, a series of polycyclic acids have been designed and synthesized as novel, potent, and selective inhibitors of human 11beta-HSD-1. Structure-activity relationships of two different regions of the chemotype (polycyclic ring and substituents on quaternary carbon) are discussed. PMID- 21983440 TI - One-class classification as a novel method of ligand-based virtual screening: the case of glycogen synthase kinase 3beta inhibitors. AB - A virtual screening system based on one-class classification with molecular fingerprints as descriptors is developed and tested on a series of 1226 inhibitors and 209 noninhibitors of glycogen synthase kinase 3beta (GSK-3beta). The suggested system outperforms the ones based on pharmacophore hypothesis and molecular docking in a retrospective study. However, in a prospective study it should not be used as a sole classifier. The system is exceptionally useful for the identification of new scaffolds among the virtual screening results obtained with other methods. PMID- 21983441 TI - Effect of the leukotriene A4 hydrolase aminopeptidase augmentor 4 methoxydiphenylmethane in a pre-clinical model of pulmonary emphysema. AB - The leukotriene A(4) hydrolase enzyme is a dual functioning enzyme with the following two catalytic activities: an epoxide hydrolase function that transforms the lipid metabolite leukotriene A(4) to leukotriene B(4) and an aminopeptidase function that hydrolyzes short peptides. To date, all drug discovery efforts have focused on the epoxide hydrolase activity of the enzyme, because of extensive biological characterization of the pro-inflammatory properties of its metabolite, leukotriene B(4). Herein, we have designed a small molecule, 4 methoxydiphenylmethane, as a pharmacological agent that is bioavailable and augments the aminopeptidase activity of the leukotriene A(4) hydrolase enzyme. Pre-clinical evaluation of our drug showed protection against intranasal elastase induced pulmonary emphysema in murine models. PMID- 21983442 TI - Synthesis and structure-activity relationship studies of dihydronaphthyridinediones as a novel structural class of potent and selective PDE7 inhibitors. AB - The synthesis and SAR studies of a series of structurally novel inhibitors of PDE7 are discussed. The best compounds from the series display low nanomolar inhibitory activity and are selective versus other PDE isoenzymes. PMID- 21983443 TI - Discovery and synthesis of novel substituted benzocoumarins as orally active lipid modulating agents. AB - The synthesis of a series of benzocoumarin keto-enamine schiff bases is reported. The novel compounds were evaluated for their antihyperlipidemic activity in the hyperlipidemic hamster model. The compound 11 at a dose of 10 mg/kg body weight significantly lowered the plasma triglyceride levels (TG) by 70%, total cholesterol (TC) by 47%, accompanied by an increase in HDL-C/TC ratio by 80% in hyperlipidemic hamsters to a greater degree than the reference drugs atorvastatin and lovastatin. PMID- 21983444 TI - Discovery of 3-hydroxy-4-cyano-isoquinolines as novel, potent, and selective inhibitors of human 11beta-hydroxydehydrogenase 1 (11beta-HSD1). AB - Derived from the HTS hit 1, a series of hydroxyisoquinolines was discovered as potent and selective 11beta-HSD1 inhibitors with good cross species activity. Optimization of substituents at the 1 and 4 positions of the isoquinoline group in addition to the core modifications, with a special focus on enhancing metabolic stability and aqueous solubility, resulted in the identification of several compounds as potent advanced leads. PMID- 21983445 TI - Synthesis of polyfunctionalized piperidone oxime ethers and their cytotoxicity on HeLa cells. AB - A series of twenty 2,6-diarylpiperidin-4-one O-methyloximes were synthesized with fluoro/chloro/bromo/methyl/methoxy/ethoxy/isopropyl substituents on various positions of the phenyl at C-2 and C-6 in association with/without methyl substituent on the secondary amino group and methyl/ethyl/isopropyl substituents on the active methylene centers. Regardless of their substitution all compounds predominantly exist in the chair conformation except 3m, which adopts a twist boat conformation. All the synthesized compounds were evaluated for their in vitro antiproliferative activity against human cervical carcinoma (HeLa) cell line. The cytotoxicity of the test compounds was determined by measuring the number of live cells after 24 h of treatment by MTT assay method. This preliminary SAR suggests some lead molecules 3c-f, 3j-k, 4d-g, and 4i with a scope of further structural optimization of the piperidone pharmacophore toward the development of anticancer drug synthesis. PMID- 21983446 TI - A double prodrug system for colon targeting of benzenesulfonamide COX-2 inhibitors. AB - The design, synthesis and delivery potential of a new type of benzenesulfonamide cyclo-oxygenase-2 (COX-2) inhibitor prodrug is investigated using celecoxib. The approach involves a double prodrug that is activated first by azoreductases and then by cyclization triggering drug release. We studied the intramolecular aminolysis of the acylsulfonamide. The cyclization was surprisingly rapid at physiological pH and very fast at pH 5. The prodrug is activated specifically under conditions found in the colon but highly stable in the presence of human and rodent intestinal extracts. Finally, the prototype with celecoxib was transported much more slowly in the Caco-2 transepithelial model than the parent. The design therefore shows significant promise for the site specific delivery of benzenesulfonamide COX-2 inhibitors to the colon. PMID- 21983447 TI - Synthesis of purine modified 2'-C-methyl nucleosides as potential anti-HCV agents. AB - Based on the anti-hepatitis C activity of 2'-C-methyl-adenosine and 2'-C-methyl guanosine, a series of new modified purine 2'-C-methyl nucleosides was prepared as potential anti-hepatitis C virus agents. Herein, we report the synthesis of both 6-modified and 2-modified purine 2'-C-methyl-nucleosides along with their anti-HCV replication activity and cytotoxicity in different cells. PMID- 21983448 TI - Skin lesions in a 16-month-old toddler with impaired zinc absorption. AB - Acrodermatitis enteropathica is a rare, autosomal recessive condition which results from impaired zinc absorption in the gastrointestinal tract. We report a 16-month-old female patient with a 7-month history of periorificial and acral skin lesions. Diagnosing of Acrodermatitis enteropathica was established on the basis of the patient's history as well as clinical and laboratory findings (a lowered zinc level in the child's serum: 17.2MUg/dL (N 70-160 MUg/dL)). Rapid clinical improvement was observed right after launching zinc supplementation. PMID- 21983449 TI - Peripheral blood mononuclear cells from patients with systemic sclerosis spontaneously secrete increased amounts of vascular endothelial growth factor (VEGF) already in the early stage of the disease. AB - PURPOSE: To investigate the capacity of the peripheral blood mononuclear cells (PBMC) from patients with systemic sclerosis (SSc) to produce vascular endothelial growth factor (VEGF), and to identify clinical associations of altered production of VEGF by PBMC in SSc. In addition, correlation with another pro-angiogenic cytokine, TNF-related weak inducer of apoptosis (TWEAK), was evaluated. METHODS: PBMC were isolated from 25 patients with SSc and 17 healthy controls (HC). VEGF and TWEAK were measured in the supernatants of cultured PBMC using commercially available ELISA kits. RESULTS: PBMC from SSc patients spontaneously released significantly greater amounts of VEGF as compared with HC. Production of VEGF was comparable between patients with early SSc and those with longer disease duration, and in both SSc groups higher than in HC. Patients without active digital ulcers produced significantly greater amounts of VEGF as compared with HC, while there was no significant difference in the production of VEGF between SSc patients with active digital ulcers and HC. VEGF/TWEAK ratio was significantly higher in PBMC from SSc patients than in HC indicating that high production of VEGF is not paralleled by increased release of TWEAK in SSc. CONCLUSIONS: PBMC form SSc patients produce increased amounts of VEGF already in the early stage of disease. There is an imbalance in the profile of pro angiogenic mediators produced by PBMC in SSc which might contribute to the pathogenesis of SSc. Further studies should address clinical significance of our findings. PMID- 21983450 TI - Iatrogenic femoral pseudoaneurysms - a simple solution of inconvenient problem? AB - PURPOSE: A femoral artery pseudoaneurysm - is the most common complication associated with invasive coronary interventions. The aim of the study was to analyze the effectiveness of various methods used for femoral pseudoaneurysm treatment and to assess how routine use of radial approach leads to reduction of these site complications. METHODS: The study comprised 1854 consecutive patients who were hospitalized in years 2005-2008 and underwent coronary angiography (with or without angioplasty) via femoral artery access. Since 2009 routine radial approach has been introduced for both coronary angiography and angioplasty. In patients with symptoms suggesting entry site complications Doppler ultrasound was performed. RESULTS: Femoral access site complications requiring additional procedures were observed in 63 patients (3.4%): in 56 femoral pseudoaneurysms (88.8%) and in 7 arteriovenous fistulas (11.1%) were diagnosed (all appeared after coronary angioplasty). The patients were treated in following ways: standard compression with an elastic bandage prolonged to 12 hours - in 14 cases (25%), ultrasound guided compression - in 13 patients (23.2%), finger compression followed by standard compression with an elastic bandage prolonged to 12 hours or ice compress - in 10 patients (17.8%), surgical treatment - in 3 patients (5.3%). Only 2 patients required thrombin injection (3.6%). Since the time routine radial approach was introduced extreme reduction in the rate of local complications was registered. CONCLUSION: Although iatrogenic femoral pseudoaneurysms following invasive percutaneous coronary interventions are still important complications, most of them can be treated conservatively. It seems that radial access completely eliminates the risk of this complication. PMID- 21983451 TI - Urinary OPN excretion in children with glomerular proteinuria. AB - PURPOSE: The aim of the study was to investigate urinary levels and clinical significance of osteopontin (uOPN) in children with different glomerular diseases according to histological diagnosis and degree of proteinuria. MATERIALS AND METHODS: The examinations were conducted in 3 groups of children: I - 20 children with minimal change disease (MCD) examined twice: A - in relapse; B - in remission, group II - 17 children with focal segmental glomerulosclerosis (FSGS), III - 12 children with IgA nephropathy (IgAN). The control group (C) contained 20 healthy children. OPN was measured in the urine using ELISA commercial available kit (R&D Quantikine) and was expressed in ng/ mg cr. RESULTS: The median uOPN/ cr. in MCD children in relapse (IA) was median 134.98 ng/ mg cr. and was higher when compared to controls (p< 0.01). In exam IB, when proteinuria subsided, OPN/ cr. increased to median 172.96 ng/ mg cr. and was higher in comparison to healthy subjects (p< 0.01) and MCD children in relapse (p<0.05). Children from group II revealed higher uOPN/ cr. levels when compared to groups I, III and C (p< 0.01). UOPN/ cr. positively correlated with protein/ creatinine ratio in all examined groups of children (p< 0.01). CONCLUSION: We found significantly higher uOPN/ cr. in all the groups of children with glomerulonephritis. The highest uOPN/ cr. levels were found in patients with FSGS and correlated significantly with both interstitial changes and mesangial expansion found in kidney biopsy. PMID- 21983452 TI - Morphological changes of the vocal fold mucosa in hyperfunctional dysphonia diagnosed by psychoacoustic and videostroboscopic methods. AB - PURPOSE: The aim of the study was to provide a morphological assessment of the laryngeal mucosa in patients with hyperfunctional dysphonia diagnosed by psychoacoustic and videostroboscopic methods. MATERIAL AND METHODS: Forty patients with voice quality disorders of hyperfunctional dysphonia were recruited for participation in the study. The diagnosis of dysphonia was based on the Voice Rating Scale GRBAS, and endoscopic and stroboscopic assessment of the vocal folds. Acoustic assessment was carried out using following parameters: fundamental frequency, Jitter, Shimmer, Noise to Harmonic Rate and Yanagihara (YG) scale. In order to evaluate the morphology of the vocal fold mucosa transmission electron microscopy was performed using postoperative material obtained from the larynx. Results of clinical and morphological analysis were compared with the reference group. The morphological material was obtained from patients with hypopharyngeal cancer without pathological changes of the vocal folds. RESULTS: The psychoacoustic assessment using the perceptual GRBAS scale enables the appropriate diagnostics of hyperfunctional dysphonia, which was confirmed by evaluation of acoustic parameters and YG scale analysis. In 40 patients with voice quality disorders causing by hyperfunctional dysphonia, in morphological assessment of the laryngeal mucosa, 4 (10%) patients demonstrated the presence of oedema and signs of intensive dysphonia in psychoacoustic and stroboscopic examination. CONCLUSIONS: Oedema of the laryngeal mucosa confirmed by stroboscopic and ultramorphological examination may coexist with hyperfunctional dysphonia. The presence of the laryngeal oedema in patients with hyperfunctional dysphonia has the negative impact on voice quality in psychoacoustic assessment with the use of the GRBAS and YG scales. PMID- 21983453 TI - High glucose impairs EDHF-mediated dilation of coronary arterioles via reduced cytochrome P450 activity. AB - Endothelium-derived hyperpolarizing factor (EDHF) is an important vasodilator that regulates the vasomotor function. However, it remains unclear whether diabetes/hyperglycemia-induced vascular impairments extend to the EDHF. The present study aims to determine the effect of high glucose (HG) on EDHF-mediated arteriolar dilation and the underlying mechanism. Porcine coronary arterioles were isolated and pressurized for vasomotor study. Cultured porcine coronary artery endothelial cells (ECs) were used for molecular and biochemical analysis. Our results demonstrate that bradykinin (BK)-simulated arteriolar dilation is mediated by nitric oxide (NO) and EDHF pathways. Direct incubation of HG impaired vasodilation to BK but not to sodium nitroprusside (endothelium-independent vasodilator). In the presence of inhibitors of endothelial NO synthase (eNOS) and cyclooxygenase, the EDHF-mediated dilation was reduced by HG incubation. The inhibitory effect of HG was prevented by treating the vessels with superoxide scavenger Tempol. In cultured coronary endothelial cells, HG reduced endothelial epoxyeicosatrienoic acid (EET) production as well as cytochrome P450 epoxygenase (CYP) activity. Furthermore, the superoxide production was elevated in ECs after HG incubation. Pretreatment with Tempol before HG incubation prevented the increase of cellular superoxide and abolished the decrease of CYP activity. Collectively, our results suggest that, in addition to NO-mediated pathway, HG impairs the EET/EDHF-mediated vasodilation in coronary arterioles via the elevated level of superoxide leading to inhibition of CYP activity in coronary ECs. PMID- 21983454 TI - Infective and inflammatory diarrhoea: mechanisms and opportunities for novel therapies. AB - There have been significant advances in unravelling the cellular mechanisms of diarrhoea in common gut infections and colonic inflammation, as well as in the identification of targets for potential antidiarrhoeal drugs. Infective diarrhoea reflects activation of electrogenic Cl- secretion, inhibition of electroneutral NaCl absorption and in some cases, downregulation of tight junctional proteins and increased apoptosis. In colonic inflammation, diarrhoea mainly reflects impairment of colonic Na+ and Cl- absorption by inflammatory cytokines, leading to decreased water absorption. Stimulation of endogenous opiate-dependent pathways, manipulation of epithelial ion (Na+, K+ and Cl-) channels and suppression of proinflammatory cytokine production by a variety of drugs and novel molecules, offer opportunities to move evaluation of these potential antisecretory and anti-inflammatory agents from the laboratory into clinical trials. PMID- 21983455 TI - Solubility and pKa determination of six structurally related phenothiazines. AB - Solubilities of six structurally related phenothiazines, namely chlorpromazine hydrochloride, fluphenazine dihydrochloride, promazine hydrochloride, thioridazine hydrochloride, trifluoperazine dihydrochloride, and triflupromazine hydrochloride at constant pH were measured in the temperature range from 290 K to 350 K in three important drugs solvents: water, ethanol and 1-octanol using the dynamic method and UV-vis method. Dissociation constants and corresponding pK(a) values of drugs were obtained with Bates-Schwarzenbach method at temperature 298.15K in the buffer solutions. Our experimental pK(a) values for chlorpromazine hydrochloride, fluphenazine dihydrochloride, promazine hydrochloride, thioridazine hydrochloride, trifluoperazine dihydrochloride, and triflupromazine hydrochloride are 9.15, 10.01, 9.37, 8.89, 8.97, and 9.03, respectively. The basic thermal properties of pure drugs i.e. melting and solid-solid phase transition as well as glass-transition temperatures, the enthalpy of melting and phase transitions and the molar heat capacity at glass transition (at constant pressure) were measured with differential scanning microcalorimetry (DSC) technique. Molar volumes were calculated with Barton group contribution method. The experimental solubility data were correlated by means of three commonly known G(E) equations: the Wilson, NRTL and UNIQUAC with the assumption that the systems studied here have revealed simple eutectic mixtures. The root-mean-square deviations of temperature were used for the precision of the correlation. The activity coefficients of drugs at saturated solutions in each correlated binary mixture were calculated from the experimental data. These new data will help in all prediction-methods and their precision. PMID- 21983456 TI - [Outcomes of using autologous peripheral-blood stem cells in patients with chronic lower arterial insufficiency]. AB - Presented herein are the outcomes of using autologous peripheral blood stem cells (SCs) in patients with stage II V lower limb chronic obliterating diseases (according to A.V. Pokrovsky's classification). Autologous SCs had previously been stimulated by means of the recombinant granulocytic colony stimulating factor (G-CSF) for five days. On day six, we performed mobilization of the peripheral blood stem cells on the MSC+ unit by means of leukopheresis followed by intramuscular administration of half of the obtained dose into the affected extremity. The mean number of the transplanted mononuclears amounted to 6.73 +/- 2.2 x 10(9) cells, with the number of CD34+ cells averaging 2.94 +/- 2.312 x 10(7). Assessing the therapeutic outcomes at 3 and 6 months of follow-up showed a statistically significant increase in the ankle-brachial pressure index (ABPI) [being at baseline 0.59 +/- 0.04, at 3 months - 0.66 +/- 0.04 (P=0.001), and after 6 months - 0.73 +/- .08 (P=0.035)], accompanied and followed by improved measures of the treadmill test, with the pain-free walking distance at baseline equalling 102.2 +/- 11.55 m, after 3 months - 129 +/- 11.13 m (P<0.001), and after 6 months - 140 +/- 13.11 m=0.021 vs baseline). The findings of the immunohistochemical study confirmed the development of neoangiogenesis in the skeletal muscle and a 25 percent increase in the capillary-network density following administration of autologous stem cells into the muscle. The method of transplanting peripheral-blood autologous stem cells for treatment of patients presenting with distal forms of chronic obliterating insufficiency of the lower limbs proved safe and efficient. The findings obtained during this study made it possible to recommend extending the indications for its application at the expense of patients with critical ischaemia. PMID- 21983457 TI - [Administration of dalteparin in reconstructive vascular surgery]. AB - The article contains a review of the literature regarding the use of low molecular-weight heparins (LMWHs) exemplified by dalteparin in the hitherto insufficiently explored area of their implementation, i. e., during the intraoperative period in patients suff ering from atherothrombosis. Presented herein is analysis of alterations in the parameters of the plasmatic and thrombocytic links of haemostatis during intraoperative administration of various molecular-weight fractions of heparin. The obtained findings make it possible to conclude that LMWHs do off er certain advantages when used during surgical interventions in patients with atherosclerotic lesions of the arterial bed. PMID- 21983458 TI - [Role of low-dose acetylsalicylic acid in comprehensive postoperative treatment of patients with lower-limb chronic arterial insufficiency]. AB - The study comprised a total of 107 patients (all men) after endured femoropopliteal bypass grafting above the genicular fissure with a synthetic stent graft manufactured by the Gore Company for stage IIB and III chronic arterial insufficiency of the lower extremities according to the Fontain Pokrovsky classification. Group One I (control group) was composed of fifty-four patients permanently taking in the postoperative period at the out-patient stage pentoxiphylline (trental 400 mg 1 tablet 3 times daily) and xantinol nicotinate at a dose of 150 mg one tablet thrice daily. Group Two (Study Group) consisted of fifty-three patients taking after reconstructive vascular surgery at the out patient stage in addition to pentoxiphylline and xantinol nicotinate acetylsalicylic acid (cardiomagnil 75 mg 1 tablet once daily). The Control Group patients within 3 to 6 months of follow up were found to have a considerable progressing improvement of the functional abilities of the microcirculatory bed requiring in 44 (81.5%) cases hospitalization to the Surgical Department for intensive vascular therapy. Despite this fact four (7.4%) patients within the time frame from 6 to 9 months after surgery developed thrombosis of the vascular implant requiring a repeat surgical intervention. In the Study Group patients, the degree of functional capabilities of the microcirculatory bed in the postoperative period was less considerable, reaching the maximum after 10-12 months of follow up, with eighteen (34.0%) patients requiring hospitalization for additional vascular therapy to perform. There were no cases of implants' thrombosis in the Study Group patients. Pathological alterations in the functional state of the peripheral vascular bed correlated with viscosimetric indices and activity of blood platelet aggregation. The addition of antithrombocytic agents to conservative postoperative therapy considerably improved the outcomes of surgical treatment. PMID- 21983459 TI - [The nearest and remote results in treatment aneurysms of the abdominal aorta and the main arteries]. AB - In the modern literature are taken widely up questions of medical tactics at an aneurysm of abdominal aorta (AA) depending on its sizes, presence of signs and presence of risk factors. The purpose of work was studying current aneurysm illnesses in various arterial parts, developments of optimum tactics of conducting patients and its influence on the remote results of operative treatment. Into research have entered 51 patient, suffering aneurism of an aorta, it branches and other main arteries. The nearest and remote results of dynamic supervision and operative treatment have been studied. The age of patients was within the limits of from 50 till 88 years, and has on the average made 71,8 +/- 6,16. A parity men and women 8:1. Diameter AA changed from 3 up to 12 sm. Aneurysms combination met in an ascending part of an aorta, subclavian arteries, brachiochephalic trunk, carotid, iliofemoral, popliteal and limb arteries. All patients had accompanying cardial pathology. Patients have been divided into 2 groups. The first was made by 34 patients by whom resection AA has been made. Patients of the second group (17 patients) has been executed by dynamic supervision. The remote results are studied at 32 (62,7%) persons. Term of supervision has made from 6 till 168 months on the average. Postoperative lethal cases at scheduled operations were 4,7%, the general postoperative lethal cases were about - 11,7%. At the analysis of the remote results it is established, that the survival rate in a year has made 100 %, 5 years - 83,3% of patients. Average life expectancy in the given group of patients has made 76,4 +/- 4 years, that there corresponds to data the WOHC for a healthy population. Dynamic supervision in both groups has shown progressing current of aneurysms combination in all arterial parts. Our data show perspectivity of surgical treatment aneurysms of an aorta and the main arteries except for patients with multistorey aneurysmosis arteries of legs in a combination to the continued thrombosis, in which treatment we adhere conservative tactics. PMID- 21983460 TI - [Therapeutic cellular angiogenesis in treatment of peripheral artery diseases]. AB - High incidence of peripheral artery disease and limited possibilities of either open or endovascular methods of treatment, as well as low efficacy of medicamentous treatment of this pathology compel the professionals concerned to search for new methods of treatment aimed at improving the condition of the distal arterial bed, decreasing peripheral resistance and stimulating the development of the capillary network. One of the possible ways to solve this problem is the use of cellular technologies for stimulating angiogenesis. This novel and rather promising method consists in using autologous cell therapy in treatment of peripheral arterial diseases. PMID- 21983461 TI - [Analysing causes of low efficacy of ultrasonographic diagnosis of stenosing major arteries of the head in hypertensive patients]. AB - The authors analyse herein the reasonable use of ultrasonographic methods of examination of carotid arteries for diagnosis of stenosing pathology in hypertensive patients. At the stage of primary medical care of the city of Chelyabinsk, a non-selective referral of patients presenting with elevated arterial pressure to duplex ultrasonography of the carotid artery is not uncommon. Doubtful criteria of selecting the hypertensive patients who really require undergoing ultrasonography of the carotid artery result in low efficacy of the examination. PMID- 21983462 TI - [Endovascular methods of treatment for acute thromboses of lower limb arteries]. AB - The article exemplifies that a group of patients presenting with acute thrombosis of lower- limb arteries appears to belong to the severest patient cohort, whose treatment remains a difficult task for a vascular surgeon, since the solution of this problem cannot be limited to thrombectomy alone, and in the overwhelming majority of cases should be completed by removing the cause of thrombogenesis, to put it more precisely, by a reconstructive vascular operation, for instance, thromboendarterectomy (bypass grafting, prosthetic repair reconstruction), or by an endovascular procedure. All this taken into consideration compels the investigators to search for safer, minimally invasive and at the same time efficient methods of treatment. Endovascular methods aimed at restoration of the arterial lumen meet these requirements to a considerable degree. To endovascular methods of treatment for acute thromboses belong the techniques of aspiration thrombectomy, fibrinolytic thrombolysis, mechanical thrombectomy, rotational, rheolytic thrombectomy, stent-grafting or balloon angioplasty. The policy of fibrinolytic thrombolysis has found rather a wide application in clinical practice. However, the use of this technique is also limited due to a variety of currently existing large disadvantages: a long list of contraindications, labour consuming and demanding nature of the procedure (requiring to be performed 6-12 hours after the onset of the symptoms of the disease, and check-up angiography within 24-48 hours) as well as rather a high rate of early haemorrhagic complications rate (up to 10-5%). The technique of rotation mechanical thrombectomy has for a long time remained insufficiently claimed for and used more frequently in experimental activity due to the presence of a series of risk factors limiting its application (a high risk of embolism of the distal portion, haemolysis, and a vascular injury). Currently, with the advent of the devices combining rotor fragmentation with simultaneous aspiration of the thrombotic masses (Rotcirex), this method of endovascular treatment is a promising technique requiring further development and widespread use in clinical practice. PMID- 21983464 TI - Surgical management of acute pulmonary artery thromboembolism. AB - We operated on a total of twenty-seven patients presenting with acute massive thromboembolism of pulmonary arteries. The patients' mean age amounted to 38.6 +/ 9.17 years. The estimated pressure in the pulmonary artery averaged 54.2 +/- 7.15 mm Hg. A total of twenty- two thromboembolectomic procedures were performed in the setting of assisted circulation. In five patients embolectomy was carried out from a thoracotomic approach without artificial circulation. The remote period was marked by a relapse of thromboembolism, with the female patient having completely refused to undergo treatment. All the patients remain in a satisfactory condition, with the estimated pressure in the pulmonary artery maintaining at an average level of 27.05 +/- 3.11 mm Hg. PMID- 21983463 TI - [Carotid endarterectomy or carotid stenting: optimal therapeutic decision-making for patients with carotid artery stenoses]. AB - The work was aimed at comparatively studying the outcomes of carotid endarterectomy and carotid stenting for optimal therapeutic decision-making in patients presenting with carotid artery stenoses. We examined and treated a total of one hundred and sixty-seven patients. In the group of endarterectomy, we performed a total of 91 operations in 85 patients, and in the group of carotid stenting, a total of 87 stenting procedures were carried out on the internal carotid artery with cerebral protection in 82 patients. This was followed by analysing both short- and long-term outcomes with a follow-up period ranging from 1 year to 3 years. We examined the following postoperative parameters: "stroke + lethality", incidence of transitory ischaemic attacks, as well as the rate of craniocerebral neuropathy and acute myocardial infarction. In the remote period we evaluated the prevalence rate of the parameter "stroke + myocardial infarction + lethality", as well as restenosis recurrence. In the carotid-endarterectomy group, the predictors of unfavourable surgical outcomes were contralateral occlusion (p=0.048) and cardial pathology (p=0.0245). In the group of carotid stenting, these predictors turned out to be a heterogeneous atherosclerotic plaque with an uneven or ulcerated contour (p=0.004), and the degree of cerebrovascular insufficiency (p=0.005). PMID- 21983465 TI - [Methods of operative interventions in postthrombotic disease of the crus]. AB - Analysed herein are the findings of examination and outcomes of surgical management of 43 patients presenting with crural postthrombotic disease. Of these, eighteen patients were diagnosed as having stage II chronic venous insufficiency (CVI) and the remaining 25 had stage III CVI. All the patients had previously experienced acute thrombosis of deep crural veins. Eight patients had developed thrombosis during or in the immediate terms after typhoid fever, seven women in the postpartum period, and a further four women after endured operations on the organs of the abdominal cavity or small pelvis. Twelve patients had developed thrombosis after a blunt injury of the limb. In a further 12 cases, the causes of thrombosis coujinot be revealed or traced properly, thus having remained unknown. The disease duration varied form twelve months to nine years. Venous haemodynamics was studied by means of duplex scanning and phlebography, with the latter used if indicated. The prevailing role in making appropriate diagnosis was found to belong duplex scanning. Thirty-one patients were subjected to combined surgical procedures. Twelve subjects underwent single-stage operations. The main stage of the intervention in combined surgery consisted in resection of the anterior tibial vein and dissection of communicating veins of the medial surface of the crus according to the Savelyev-Konstantinova's technique; phlebectomy was performed on the crus only. The remote period was marked by a decrease in the CVI's severity, i.e., transition to a lesser-severity degree in eighteen patients (41.9 %), while in twenty-five cases (58.1 %) CVI remained at the baseline level. Totally, positive results were obtained in forty patients (93.0%). Three patients (7.0 %) initially presenting with grade C5-6 CVI and subjected to single-component operations were found to have poor outcomes. Surgical correction of the venous blood fl ow does by no means cure the patient but appears to result in persistent remission of the disease, with adequate rehabilitation after surgery leading to considerable regression of CVI. PMID- 21983466 TI - [Phlebothrombosis and congenital thrombophilia]. AB - Foreign researchers have actively been studying the eff ect of certain gene polymorphisms on the development of venous thromboembolism in various anatomical regions, with such studies being merely sporadic so far in Russia. We examined a total of one hundred and fifty-seven patients diagnosed with deep vein thrombosis and forty people constituting the control group. It was determined that the presence of the factor V Leiden mutation increased by up to 15-fold the chance of developing venous thrombosis, especially an idiopathic one and in the young age; the C7351T polymorphism of tissue plasminogen activator increased the risk of the development of idiopathic venous and early thrombosis up to 5-12-fold, whereas the C677T polymorphism of methylenetetrahydrofolate reductase increased it 2-fold only. The rest polymorphisms of the genes of the plasmatic, thrombocytic haemostasis and the folate cycle enzymes along 14 loci appeared to exert no significant influence on the development of venous thrombosis. Based on the findings obtained in the genetic analysis, it is even now possible to carry out appropriate correction of conservative therapy in patients presenting with acute and chronic venous pathology. PMID- 21983467 TI - [Oxygen provision of the brain during carotid endarterectomy in the settings of general and local anaesthesia]. AB - Based on the indices of cerebral oximetry, analysed herein is efficiency of oxygen support of the brain in various types of anaesthesiological provision (total and general anaesthesia) in patients presenting with atherosclerosis of the brachiocephalic arteries during carotid endarterectomy. It was shown that at the expense of preserving the mechanism of autoregulation, the use of local anaesthesia provides higher efficiency of cerebral perfusion than general anaesthesia which is evidenced by the values of cerebral oximetry exceeding 60% at all stages of the operation. Dynamics of cerebral oxygenation during occlusion of the carotid arteries in the setting of local anaesthesia suggests high reactivity of the cerebral vessels in this cohort of patients and hence preservation of the cerebrovascular reserve in them. PMID- 21983468 TI - [Damage to craniocerebral nerves in reconstructive surgery of carotid arteries]. AB - Reconstructive operations on aortic arch branches appear to be the most efficient method of preventing acute and chronic impairments of cerebral circulation. Iatrogenic lesions of the craniocerebral nerves deteriorate the course of the immediate, and especially the remote postoperative period, decreasing quality of life and social status of the patients after endured carotid reconstructions. The authors analysed herein the outcomes in a total of 562 patients after endured carotid artery surgery for atherosclerosis or pathological tortuosity. The authors examined the incidence rate, patterns and risk factor of damage to the craniocerebral nerves in all the patients. Comprehensive prevention of damage to the craniocerebral nerves was carried out in a total of 412 patients from the Study Group and was aimed at excluding or decreasing intensity of the eff ect of the eliminable risk factors. The proposed measures made it possible to decrease the rate of lesions of craniocerebral nerves from 18.7 to 6.9% and to substantially improve the postoperative patients' quality of life. PMID- 21983469 TI - [Operations on carotid arteries in an acute stage of ischaemic stroke]. AB - The present study was aimed at specifying the indications for operations performed on carotid arteries in an acute period of ischaemic stroke and assessing the results thus obtained. Between January 2008 and July 2010, we carried out a total of 372 operations on carotid arteries in three hundred and sixty patients. Of these, thirty-two subjects were operated on in an acute period of stroke. Neurovisualization was performed by means of magnetic resonance imaging (MRI) and computed tomography (CT). The condition of the carotid arteries was assessed by means of duplex scanning (DS). The operations performed on the carotid arteries were as follows: thrombembolectomy (n=4), carotid thrombendarterectomy (n 5), carotid endarterectomy (CEAE, n=21), and stent grafting of the internal carotid arteries (1SA, n 2). Five CEAE operations were carried out after thrombolysis. The interventions on the carotid arteries were performed within 6 hours to 12 days from the onset of the first symptoms of ischaemic stroke. Neurologists were actively engaged in both determining the indications for the operations and monitoring of neurological functions. There were no perioperative complications encountered. Regression of the neurological deficit during 7 days of in-hospital follow up occurred in sixteen patients (50%) (neurological deficit scoring 1-2 by the Rankin scale). One patient (3%) developed ischaemic stroke on postoperative day 3 after CEAE. Two patients were diagnosed as having transitory ischaemic attacks. Stenting turned out successful in the both patients. The remote results at terms ranging from 12 months to 2 years were followed up in fifteen patients. Of these, twelve patients (80%) showed complete restoration of neurological functions (Rankin scale scoring 0). Neither lethal outcomes nor relapsing strokes were observed over the follow-up period. The obtained outcomes strongly suggest certain advantages and advisability of active surgical policy of treating patients presenting in an acute stage of ischaemic stroke, with appropriate observance of the strict indications for the intervention. PMID- 21983470 TI - Peculiarities of glomus-sparing eversion carotid endarterectomy. AB - Described in the article are technical peculiarities of performing eversion carotid endarterectomy with the preservation of the structure of the carotid glomus. Atherosclerosis of the carotid artery bifurcation appears to influence the onset and course of arterial hypertension. An important role therein is played by barorefl ex and glomus dysfunction. The operation of carotid endarterectomy decreases the background arterial pressure but in a series of cases, with destroyed structures of the carotid glomus, induces alterations in the pattern of arterial hypertension with the development of hyper- and hypotensive crises. The authors have worked out an operation of glomus-sparing eversion carotid endarterectomy, combining advantages of the eversion technique and prevention of glomus dysfunction. The outcomes of 25 operations demonstrated a positive antihypertensive eff ect of the new technique, with no systemic haemodynamic impairments observed in the patients after surgery. PMID- 21983471 TI - [Formation of vertebral-subclavian steal syndrome in abnormal origin of the left vertebral artery from the aortic ark]. AB - Presented herein is a clinical case report concerning the formation of vertebral subclavian steal syndrome combined with occlusion of the left subclavian artery and an abnormal origin of the left vertebral artery from the aortic arch. Duplex scanning data and angiography findings showed that the collateral compensation of haemocirculation in the upper extremity took place through the subclavian vertebral collateral net. Doppler ultrasonography signs of the latent steal syndrome were revealed in the intracranial segment of the left vertebral artery and were confirmed by the findings of the reactive hyperthermia test. Balloon angioplasty with stenting of the 1st portion of the left subclavian artery resulted in normalization of the Doppler spectrum in the intracranial segment of the left vertebral artery. PMID- 21983472 TI - [Dual left arterior coronary artery: a case report]. AB - We report an observation of one of the rarest coronary arteries anomaly, type IV dual left arterior descending artery in 43-year-old man. The patient arrived with angina pectoris and underwent multispiral computed tomography of coronary arteries, having revealed abnormal anatomy as well as atherosclerotic lesion of coronary arteries. Hemodynamically signification stenoses were successfully eliminated by the way of coronary stending. PMID- 21983473 TI - [Clinical peculiarities of posttraumatic arteriovenous fistulas]. AB - Analysed herein are clinical manifestations of, and outcomes of successful surgical management for postoperative arteriovenous fistulas. PMID- 21983474 TI - [Experience in surgical management of posttraumatic arteriovenous aneurysms of the aortorenal zone]. AB - Presented herein are two clinical case reports concerning surgical management of posttraumatic arteriovenous aneurysms of the juxtarenal portion of the aorta and left renal vein, demonstrating the informative value of multispiral computed angiography in diagnosis of the pathology involved. Two patients presenting with a stab-and-lacerated wound of the abdominal cavity and subjected to comprehensive examination were found to have an arteriovenous anastomosis between the aorta and left renal vein with the formation of an up to 35-mm aneurysm in one case, and an arteriovenous anastomosis between the left renal artery and left renal vein with the formation of a pseudoaneurysm sized up to 30 mm in the other. Both patients had a clinical picture of cardiopulmonary insufficiency induced by overloading of the right portions of the heart. Both pathologies were treated surgically in the scope of removing the arteriovenous anastomosis and aneurysm of the juxtarenal portion of the abdominal aorta and left renal artery. The postoperative period showed nothing to report and turned out uneventful, with the patients being discharged from the clinic in a satisfactory condition with good laboratory and haemodynamic parameters. PMID- 21983475 TI - Short bouts of mild-intensity physical exercise improve spatial learning and memory in aging rats: involvement of hippocampal plasticity via AKT, CREB and BDNF signaling. AB - In the present study, we investigated whether mild-intensity physical exercise represents a successful strategy to enhance spatial learning and memory and hippocampal plasticity in aging rats, as previously described for long-term exposure to running wheel or treadmill exercise. Aging Wistar rats were submitted to short bouts (4-6 min) of exercise treadmill during five consecutive weeks. This mild-intensity exercise program increased muscle oxygen consumption by soleus and heart in aging rats and reversed age-related long-term spatial learning and memory impairments evaluated in the water maze and step-down inhibitory avoidance tasks. Remarkably, the observed cognitive-enhancing properties of short bouts of exercise were accompanied by the activation of serine/threonine protein kinase (AKT) and cAMP response element binding (CREB) pro-survival signaling that culminates in the marked increase on the brain derived neurotrophic factor (BDNF) mRNA expression and BDNF protein levels on the hippocampus of aging rats. Altogether, these results indicate that short bouts of exercise represent a viable behavioral strategy to improve cognition and synaptic plasticity in aging rats which should be taken into account in further studies addressing the effects of physical exercise in aging subjects. PMID- 21983478 TI - Distribution of entomopathogenic nematodes in Southern Cameroon. AB - A first survey of entomopathogenic nematodes (EPN) was conducted in three agro ecological zones of Southern Cameroon in 2007 and 2008. Entomopathogenic nematodes were recovered from 26 of 251 soil samples (10.4%). Three species, Heterorhabditis baujardi, Steinernema sp. A and Steinernema sp. B were found. The two steinernematids were considered unidentified species. Among the positive samples, 23 samples contained only H. baujardi (88.5%), two contained Steinernema sp. A co-occurring with H. baujardi (7.7%), and one sample contained Steinernema sp. B (3.9%). H. baujardi was frequent in forest and fruit crop (cocoa and oil palm plantations). Steinernema sp. A was found in a tree plantation of teak, Steinernema sp. B in a forest habitat. Nematodes were mostly present in acidic soils with pH ranging from 3.7 to 7.0. The highest EPN presence was recorded in sandy loam, sandy clay loam, sandy clay and clay soils. EPNs were not recovered in sand, loamy sand and clay loam soils. Using principal component analysis for elucidating the major variation patterns among sampling sites, four factors explaining for 73.64% of the overall variance were extracted. Factors were a combination of geographical (latitude, longitude, altitude), soil (pH, contents of sand, silt and clay, organic carbon, texture), and moisture (wilting point, field capacity) parameters as well as climatic parameters (mean annual rainfall, mean air temperature). Logistic regression and redundancy analyses (RDA) revealed that soil pH, longitude, available water and altitude were associated with presence and absence of EPN. Both logistic regression and RDA indicated that, increasing soil pH and longitude, associated with decreasing altitude, led to higher percentages of samples containing entomopathogenic nematodes. PMID- 21983476 TI - Initial RCT of a distress tolerance treatment for individuals with substance use disorders. AB - BACKGROUND: Psychological distress tolerance, the ability to persist in goal directed activity when experiencing psychological distress, is associated with poor substance use treatment outcomes including drug and alcohol treatment dropout and relapse. OBJECTIVE: The current study examines if a brief distress tolerance intervention that was specifically developed as an adjunctive treatment for patients in residential substance abuse treatment shows efficacy in improving the patients' distress tolerance. METHODS: Seventy-six individuals who were receiving treatment at a residential substance use treatment facility and indexed low distress tolerance on laboratory distress tolerance measures were randomized into three conditions: treatment-as-usual (TAU), six sessions of Supportive Counseling (SC), or six sessions of the novel distress tolerance treatment, Skills for Improving Distress Intolerance (SIDI). MEASURES: Patients were assessed at baseline for DSM-IV psychiatric diagnoses, DSM-IV substance use disorders, distress tolerance, and depressive symptoms. Patients were again assessed at posttreatment. Therapeutic alliance and treatment expectancies and credibility were also assessed at posttreatment. RESULTS: Patients who received SIDI (n=28) evidenced significantly greater improvements than SC (n=24) and TAU participants (n=24) on the distress tolerance laboratory measures, even when controlling for changes in negative affect (in the form of depression). Additionally, a higher percentage of patients in SIDI reached clinically significant improvement compared to patients in SC and TAU. CONCLUSION: This study supports the efficacy of SIDI in improving distress tolerance levels among individuals with drug and alcohol use disorders currently receiving residential substance use treatment. SIDI appears to be a brief and feasible intervention for use within inpatient substance use facilities. PMID- 21983479 TI - Cerebral language reorganization in the chronic stage of recovery: a longitudinal fMRI study. AB - The goal of the present study was to investigate whether spontaneous functional recovery following insult to the language-dominant hemisphere continues in the so called "chronic stage," and if so, to examine its neuro-functional correlates. We used a longitudinal functional magnetic resonance imaging (fMRI) block design, where each young patient served as his/her own control. Specifically, we examined whether language functions differed significantly in two monitoring sessions conducted years apart, both in the chronic stage, where almost no functional changes are expected. We focused on a unique cohort of young brain damaged patients with aphasiogenic lesions occurring after normal language acquisition, in order to maximize the potential of plasticity for language reorganization following brain damage. The most striking finding was that the linguistic recovery of our patients was significant not just relative to their linguistic scores on initial testing (T1), but also in absolute terms, relative to the respective age-matched normal population. Such improvement, therefore, cannot be simply attributed to the natural process of development. Overall, we found that right hemisphere (RH) activation was associated with better recovery in the chronic stage. Our longitudinal findings may challenge the view of recovery as ending within the first year following onset, suggesting that the RH may provide the substrate for ongoing plasticity in the damaged brain. PMID- 21983480 TI - Analysis of stress-induced hepatic gene expression in rainbow trout (Oncorhynchus mykiss) selected for high- and low-responsiveness to stress. AB - The production and welfare of intensively reared fish would be improved by reducing stress responsiveness. One approach to achieving this goal is selective breeding utilising stress-responsive genes as direct genetic markers of the desirable trait. As a first step in this process, microarray analysis has been carried out on liver tissues of rainbow trout selectively bred for high (HR) or low (LR) responsiveness to a stressor. Microarray hybridizations provided gene expression profiles for pooled samples of fish confined for 6 h, 24 h and 168 h and for individual fish (168 h only). 161 genes were shown to be differentially regulated in HR and LR fish during confinement exposure and eight of these gene expression profiles were validated by quantitative PCR. Genes of particular interest included intelectin-2 precursor which showed greater than 100-fold higher expression in HR fish compared to LR fish irrespective of whether the fish were confined or not; interferon inducible transmembrane protein 3 which was differentially stress-induced between the two lines; and hepatic pro opiomelanocortin B (POMC B) which was upregulated during stress in HR fish but downregulated in LR fish. All these offer potential as direct markers of low stress responsiveness in a marker-assisted selection scheme. PMID- 21983481 TI - Diagnostic value, clinical utility and pathogenic significance of reactivity to the molecular targets of Crohn's disease specific-pancreatic autoantibodies. AB - Pancreatic autoantibodies (PAB) giving characteristic staining patterns of the exocrine pancreas by indirect immunoflourescence appear to be specific markers of Crohn's disease (CrD), being present in approximately 30% of patients with CrD and in less than 5% of patients with ulcerative colitis (UC). Some studies have suggested that PAB are associated with specific disease phenotypes and that their detection may be of clinical significance. Thorough investigation of the role of PAB in the immunopathogenesis of inflammatory bowel diseases (IBD) has been hampered due to the lack of identity of their antigenic targets. The recent identification of the pancreatic zymogen granule protein 2 (GP2) as the major target of PAB has led to the development of an enzyme immunoassay that helps determine the diagnostic and clinical relevance of antigen-specific immune responses. Recent studies have demonstrated that GP2 is expressed on the apical surface of intestinal membranous cells of the follicle-associated epithelium, and is essential for host-microbial interaction and the initiation of bacteria specific mucosal immune responses. This review critically discusses recent reports investigating the diagnostic and clinical utility of GP2-specific autoantibody responses in patients with IBD. Hints towards a better understanding of the immunogenicity of GP2 are also provided. PMID- 21983482 TI - An image-based skeletal model for the ICRP reference adult male-specific absorbed fractions for neutron-generated recoil protons. AB - Recoiling hydrogen nuclei are a principle mechanism for energy deposition from incident neutrons. For neutrons incident on the human skeleton, the small sizes of two contrasting media (trabecular bone and marrow) present unique problems due to a lack of charged-particle (protons) equilibrium. Specific absorbed fractions have been computed for protons originating in the human skeletal tissues for use in computing neutron dose response functions. The proton specific absorbed fractions were computed using a pathlength-based range-energy calculation in trabecular skeletal samples of a 40 year old male cadaver. PMID- 21983483 TI - Oral toxicological studies of black soybean (Glycine max) hull extract: acute studies in rats and mice, and chronic studies in mice. AB - Black soybean (Glycine max) has been used for traditional medicine and food in Asian countries, but safety of its hull has not been studied. We conducted acute and chronic oral toxicity studies. For the acute study, an extract of black soybean hull (BE; 2.5 g/kg body weight) was administered singly by intragastric intubation to Sprague-Dawley rats and C57BL/6 mice. There was no death or significant decrease in body weight in rats and mice, and the oral LD(50) of BE was >2.5 g/kg body weight. In the chronic study, BE was administered at dietary levels of 0% (control), 2.0%, and 5.0% to male and female C57BL/6 mice for 26 weeks. No mortality or toxicologically significant clinical changes were observed through the experimental period. Although body weights, as well as abdominal fat, blood levels of triglyceride and total cholesterol in 5.0% males were significantly lower than that in control and 2.0% groups, these changes were considered not to be adverse. Hematology and histopathological observation revealed no toxicologically significant changes. The no-observed adverse-effect level of BE was estimated to be 5.0% in the diet (5074.1 mg/kg body weight/day for males and 7617.9 mg/kg body weight/day for females). PMID- 21983484 TI - The fate of ingredients in and impact on cigarette smoke. AB - A series of experiments are described, undertaken on both volatile and non volatile ingredients either during cigarette smoking or under pyrolysis conditions that try to simulate cigarette smoking. In particular, the fate of a series of deuterium and (13)C labelled volatiles was studied which demonstrated that, in a similar way to unlabelled volatiles, a large proportion of each was transferred intact into mainstream smoke. The unaccounted material, which was not transferred intact, in the studies of both volatile and non-volatile ingredients was primarily transformed into products of complete combustion such as carbon monoxide or carbon dioxide with only very minor amounts transformed into products of incomplete combustion. In addition, the studies on both unlabelled and deuterium labelled compounds demonstrated that the utility of pyrolysis studies lies mainly in distinguishing between those compounds that transfer intact into mainstream smoke from those that might be liable to degrade. Pyrolysis does not provide a robust prediction of the compounds that are formed from ingredients during cigarette smoking studies. PMID- 21983485 TI - Amelioration of collagen-induced arthritis by Salix nigra bark extract via suppression of pro-inflammatory cytokines and oxidative stress. AB - Our study goals to investigate the anti-arthritic potential of Salix nigra bark methanol extract (SNME) against both inflammation and oxidative stress in the collagen-induced arthritis (CIA) rat model. Results showed that SNME exhibited maximum scavenging activity against superoxide, hypochlorous acid and hydrogen peroxide radicals along with the suppression of lipid peroxidation. Female wistar rats were immunized with porcine type II collagen and treated with SNME (100 mg/kg body weight) for 15 days starting on day 20. SNME significantly inhibited the paw swelling and arthritic score; exhibited maximum CIA inhibition of 93.7% by the end of the experimental period. Administration of SNME to arthritic rats significantly improved the histological findings in joints as evident by reduced infiltration of polymorphonuclear cells and smooth synovial lining. Roentgenograms of tibiotarsal joints of both SNME and indomethacin-treated rats showed protection against osteophyte formation, soft tissue swelling and bone resorption. Furthermore, levels of inflammatory mediators (nitric oxide, TNF alpha, IL-1beta, IL-6) measured in both plasma and joint exudates were significantly reduced by SNME treatment. Increased oxidative stress observed in the arthritic animals was also found to be significantly restored in SNME- treated rats. Taken together, our studies clearly indicate the potential of S. nigra as an anti-arthritic agent. PMID- 21983486 TI - Safety assessment of Cissus quadrangularis extract (CQR-300): subchronic toxicity and mutagenicity studies. AB - Cissus quadrangularis has been used for centuries for therapeutic and culinary purposes. Extract from this plant (CQR-300) has been claimed for its health benefits. The objective of present investigation was to delineate adverse effects, if any, of CQR-300 in subchronic toxicity, and gentotoxicity studies. In the subchronic study, Sprague Dawley rats (20/sex/group) were administered (gavage) C. quadrangularis extract (CQR-300) at dose levels of 0, 100, 1000, and 2500 mg/kg body weight (bw)/day for 90 days. No treatment related clinical signs of toxicity, mortality or changes in body weights, body weight gain or food consumption were noted. Functional observation tests and ophthalmological examination did not reveal any changes. No toxicologically significant treatment related changes in hematological, clinical chemistry, urine analysis parameters, and organ weights were noted. No treatment related macroscopic and microscopic abnormalities were noted at the end of treatment period. The results of mutagenicity studies as evaluated by Ames assay, in vitro chromosomal aberration and in vivo micronucleus assay did not reveal any genotoxicity of CQR-300. Based on the subchronic study, the no-observed-adverse-effect level (NOAEL) for C. quadrangularis extract (CQR-300) determined as 2500 mg/kg bw/day, the highest dose tested. PMID- 21983487 TI - Hepatoprotective activity of Andrographis paniculata and Swertia chirayita. AB - Andrographis paniculata (Family: Acanthaceae) and Swertia chirayita (Family: Gentianaceae) are two controversial medicinal plants used as Kiriyattu, having similar therapeutic action and are used as a hepatoprotective and hepatostimulative agent. A. paniculata grows in southern parts of India and S. chirayita in the Himalayan region. The present work concerns on the ability of the extracts of these plants to offer protection against acute hepatotoxicity induced by paracetamol (150 mg/kg) in Swiss albino mice. Oral administration of A. paniculata or S. chirayita extract (100-200mg/kg) offered a significant dose dependent protection against paracetamol induced hepatotoxicity as assessed in terms of biochemical and histopathological parameters. The paracetamol induced elevated levels of serum marker enzymes such as serum glutamate pyruvate transaminase (GPT), serum glutamate oxaloacetate transaminase (GOT), alkaline phosphatase (ALP), and bilirubin in peripheral blood serum and distorted hepatic tissue architecture along with increased levels of lipid peroxides (LPO) and reduction of superoxide dismutase (SOD), catalase, reduced glutathione (GSH) and glutathione peroxidase (GPx) in liver tissue. Administration of the plant extracts after paracetamol insult restored the levels of these parameters to control (untreated) levels. Thus the present study revealed that the extracts of A. paniculata or S. chirayita offered protection against hepatotoxicity induced by paracetamol. PMID- 21983488 TI - Evidence for alteration of calpain/calpastatin system in PBMC of cystic fibrosis patients. AB - We are here reporting that in peripheral blood mononuclear cells (PBMC) of patients homozygous for F508del-CFTR the calpain-calpastatin system undergoes a profound alteration. In fact, calpain basal activity, almost undetectable in control PBMC, becomes measurable at a significant extent in cells from cystic fibrosis (CF) patients, also due to a 40-60% decrease in both calpastatin protein and inhibitory activity. Constitutive protease activation in CF patients' cells induces a large accumulation of the mutated cystic fibrosis transmembrane conductance regulator (CFTR) in the 100kD+70kD split forms as well as a degradation of proteins associated to the CFTR complex. Specifically, the scaffolding protein Na(+)/H(+) exchanger 3 regulatory factor-1 (NHERF-1) is converted in two distinct fragments showing masses of 35kD and 20kD, being however the latter form the most represented one, thereby indicating that in CF PBMC the CFTR complex undergoes a large disorganization. In conclusion, our observations are providing new information on the role of calpain in the regulation of plasma membrane ion conductance and provide additional evidence on the transition of this protease activity from a physiological to a pathological function. PMID- 21983489 TI - Triple negative breast cancer: proposals for a pragmatic definition and implications for patient management and trial design. AB - In trials in triple negative breast cancer (TNBC), oestrogen and progesterone receptor negativity should be defined as < 1% positive cells. Negativity is a ratio of <2 between Her2 gene copy number and centromere of chromosome 17 or a copy number of 4 or less. In routine practice, immunohistochemistry is acceptable given stringent quality assurance. Triple negativity emerging after neoadjuvant treatment differs from primary TN and such patients should not enter TNBC trials. Patients relapsing with TN metastases should be eligible even if their primary was positive. Rare TN subtypes such as apocrine, adenoid-cystic and low-grade metaplastic tumours should be excluded. TN and basal-like (BL) signatures overlap but are not equivalent. Since the significance of basal cytokeratin or EGFR overexpression is not known and we lack validated assays, these features should not be used to subclassify TN tumours. Tissue collection in trials is mandatory so the effect on outcome of different tumour phenotypes and BRCA mutation can be explored. No prospective studies have established that TN tumours have particular sensitivity or resistance to any specific chemotherapy agent or radiation. TNBC patients should be treated according to tumour and clinical characteristics. PMID- 21983490 TI - Reduction of ochratoxin A in broiler serum and tissues by Trichosporon mycotoxinivorans. AB - The present study was planned to evaluate the possible transmission of ochratoxin A (OTA) in serum and targeted organs of broilers fed on two levels (500 and 1000 ppb) this toxin in the presence or absence of a toxin deactivator (containing a mycotoxin deactivating yeast Trichosporon mycotoxinivorans) at two inclusion levels (1 and 2 kg/ton of feed) to 270 day-old broiler chicks divided into nine groups (A-I) over a 42 days period. Serum samples were collected at 14, 28 and 42nd day of experiment, whereas, liver and kidney tissues were obtained from broilers slaughtered at 42nd day of experiment. The highest OTA levels were detected in serum, livers and kidneys of OTA treated groups without supplementation of toxin deactivator (groups D and G) at day 42 of experiment, while the residues were significantly (P<0.01) lower in treatment groups (F and I) supplemented with toxin deactivator at 2 kg/ton of feed. The order of OTA level was serum>kidneys>liver. PMID- 21983491 TI - Mitochondrial bioenergetic function and metabolic plasticity in stem cell differentiation and cellular reprogramming. AB - BACKGROUND: The self-renewal ability and pluripotent differentiation potential of stem cells hold great promise for regenerative medicine. Many studies focus on the lineage-specific differentiation and expansion of stem cells, but little is known about the regulation of glycolysis and mitochondrial biogenesis and function during these processes. Recent studies have demonstrated a strong correlation between cellular metabolism and the pluripotency and differentiation potential of stem cells, which indicates the importance of bioenergetic function in the regulation of stem cell physiology. SCOPE OF REVIEW: We summarize recent findings in the control of stem cell competence through the regulation of bioenergetic function in embryonic, hematopoietic, mesenchymal, and induced pluripotent stem cells, and discuss the up-to-date understanding of the molecular mechanisms involved in these biological processes. MAJOR CONCLUSIONS: It is believed that the metabolic signatures are highly correlated with the stemness status (high glycolytic flux) and differentiation potential (mitochondrial function) of stem cells. Besides, mitochondrial rejuvenation has been observed to participate in the reprogramming process. GENERAL SIGNIFICANCE: Understanding the metabolic regulation of stem cells will have great value in the characterization and isolation of stem cells with better differentiation potential. It also provides novel strategies of metabolic manipulation to increase the efficiency of cellular reprogramming. This article is part of a Special Issue entitled Biochemistry of Mitochondria, Life and Intervention 2010. PMID- 21983492 TI - Characterizing the behavioral effects of nerve agent-induced seizure activity in rats: increased startle reactivity and perseverative behavior. AB - The development and deployment of next-generation therapeutics to protect military and civilian personnel against chemical warfare nerve agent threats require the establishment and validation of animal models. The purpose of the present investigation was to characterize the behavioral consequences of soman (GD)-induced seizure activity using a series of behavioral assessments. Male Sprague-Dawley rats (n=24), implanted with a transmitter for telemetric recording of encephalographic signals, were administered either saline or 1.0 LD50 GD (110 MUg/kg, sc) followed by treatment with a combination of atropine sulfate (2 mg/kg, im) and the oxime HI-6 (93.6 mg/kg, im) at 1 min post-exposure. Seizure activity was allowed to continue for 30 min before administration of the anticonvulsant diazepam (10 mg/kg, sc). The animals that received GD and experienced seizure activity had elevated startle responses to both 100- and 120 dB startle stimuli compared to control animals. The GD-exposed animals that had seizure activity also exhibited diminished prepulse inhibition in response to 120 dB startle stimuli, indicating altered sensorimotor gating. The animals were subsequently evaluated for the acquisition of lever pressing using an autoshaping procedure. Animals that experienced seizure activity engaged in more goal directed (i.e., head entries into the food trough) behavior than did control animals. There were, however, no differences between groups in the number of lever presses made during 15 sessions of autoshaping. Finally, the animals were evaluated for the development of fixed-ratio (FR) schedule performance. Animals that experienced GD-induced seizure activity engaged in perseverative food trough directed behaviors. There were few differences between groups on other measures of FR schedule-controlled behavior. It is concluded that the GD-induced seizure activity increased startle reactivity and engendered perseverative responding and that these measures are useful for assessing the long-term effects of GD exposure in rats. PMID- 21983493 TI - Levels of cerebrospinal fluid neurofilament light protein in healthy elderly vary as a function of TOMM40 variants. AB - Neurofilament light (NFL) proteins in cerebrospinal fluid (CSF) are a marker of neuronal damage, especially subcortical axonal injury and white matter disease. Subjects with Alzheimer's disease (AD) have shown elevated levels of CSF NFL as compared to controls. However, the presence of the APOE epsilon4 allele, an established risk factor for AD, was not found to associate with higher CSF NFL concentrations. We examined whether TOMM40 variants, which have been reported to influence age of onset of AD and are in linkage disequilibrium with APOE, have an effect on CSF NFL levels, in 47 healthy, cognitively intact individuals with or without APOE epsilon4. Our results show that the presence of APOE epsilon4 alone does not affect CSF NFL levels significantly; however APOE and TOMM40 appear to interact. Subjects with APOE epsilon4 have higher CSF NFL levels than non epsilon4 carriers, only when they do not carry a short poly-T variant of TOMM40, which is associated with later age of onset of AD, and may act as protective against the dose effect of epsilon4. PMID- 21983494 TI - Age- and disease-related innate immunity of human leukocytes ex vivo. AB - Two mechanisms of innate immunity, i.e. resistance to viral infection and the production of cytokines by leukocytes, were compared in blood isolated from four groups of donors: healthy young (19-35 years old), healthy elderly (over 60), elderly Alzheimer's disease (AD) patients, and elderly patients with alimentary tract cancer (CA). Peripheral blood leukocytes (PBLs) were isolated by gradient centrifugation in Gradisol G. The degree of resistance was calculated from the kinetics of vesicular stomatitis virus (VSV) replication in the PBLs. Cytokine (TNFalpha, IFNalpha, IFNgamma, IL-12, and IL-10) levels were determined by ELISA. The antiviral resistance of the PBLs varied, but a difference was observed only between the young and elderly groups and not between the healthy elderly controls and those with AD or cancer. Differences observed in all the groups concerned the ability and intensity of cytokine production. The most impressive results were obtained for spontaneous TNF and IFNalpha release. While TNF was released spontaneously by the PBLs of the elderly CA patients and the young healthy group, it was usually undetected in the AD and only sometimes in the healthy elderly group. Leukocytes isolated from the elderly groups responded to VSV infection with more intense IFNalpha and IFNgamma production than the younger group. PMID- 21983497 TI - Medication adherence and subjective weight perception in patients with first episode psychotic disorder. AB - INTRODUCTION: Medication adherence is critical to the management of psychotic disorder. Different factors associated with medication adherence have been investigated in previous studies. However, the association with subjective weight perception, which is related to the weight gain side effect of antipsychotics, has not been thoroughly investigated. Subjective weight perception may not equal objective weight status. This study tests the hypothesis that medication adherence is related to subjective weight perception in a group of patients with first-episode psychotic disorder who have taken antipsychotics for one year. METHODS: This study recruited 160 participants with one-year histories of first episode psychotic disorder and measured their actual and perceived weights, amount of weight gain in the past year, body size satisfaction and medication adherence levels. The associations between medication adherence and both the actual and perceived weight status were analyzed controlling for other confounding factors including insight, drug attitude, illness severity and other medication side effects. RESULTS: Stepwise multiple regression analysis found that the participants' perceived weight status, negative attitude toward their drugs and insight were the major factors associated with poor medication adherence. Of the participants who perceived themselves as being overweight, 86% believed that antipsychotics were responsible. Among those who had such beliefs, 72% had reduced their antipsychotic dosages on their own. About half of the participants had gained more than 7% of their baseline weight and 43.1% of the participants were found to be overweight after one year of treatment with antipsychotics. CONCLUSIONS: The results of this study indicate that medication adherence is associated with perceived weight status. Healthcare professionals should be aware of this relationship and address this issue early in the management of patients. Apart from weight management programs, education on a correct weight perception should be carried out with the promotion of proper drug attitudes and better insight for the improvement of medication adherence in the early course of psychotic disorder. PMID- 21983496 TI - Concomitant psychotropic medication use during treatment of schizophrenia patients: longitudinal results from the CATIE study. AB - OBJECTIVE: This study is a post hoc analysis of additions of antidepressants, anxiolytics, and sedative/hypnotics in treatment of patients randomized to antipsychotic treatment in the CATIE study, which recruited a chronic, "real world" schizophrenia sample and followed patients for up to eighteen months. We examined baseline predictors of initiation, time until initiation, and duration of treatment with antidepressants, anxiolytics, and sedative/hypnotics in CATIE study participants. METHODS: Psychotropic medication use by 1,449 CATIE study participants was documented at each study visit. Baseline demographic and clinical predictors of initiation, of time to initiation, and of duration of treatment of Concomitant Psychotropic Medications (CPMs) in each category (antidepressant, anxiolytic, and sedative/hypnotics) were identified through multiple regression analyses. RESULTS: Initiation of new CPMs post baseline by CATIE clinicians was moderately frequent, with 14.6% of patients receiving antidepressants, 13.7% receiving anxiolytics, and 11.2% receiving sedative/hypnotics. Predictors of antidepressant initiation (14.6% of group) were being female or white, and having a prior diagnosis of depression or symptoms of depression at baseline. Patients with higher positive symptom scores and younger patients were started on antidepressants sooner. Duration of antidepressant treatment was longer in patients with less education and in those with a history of alcohol abuse/dependence. Predictors of anxiolytic initiation (13.7% of group) were not being of African-American race, being separated/divorced, younger age, higher body mass index, and akathisia. Time to anxiolytic initiation was shorter in patients who were separated or divorced and in patients with better neurocognitive functioning. Duration of anxiolytic treatment was shorter for African Americans and longer in patients with better instrumental role functioning. Predictors of sedative/hypnotic use (11.2% of group) were depressive symptoms and prior diagnosis of an anxiety disorder. Time to initiation of sedative/hypnotics was longer for those with depressive symptoms and shorter for those with a history of alcohol abuse/dependence. CONCLUSIONS: Sedative/hypnotics, anxiolytics, and antidepressants were commonly used CPMs in schizophrenia during the CATIE trial, where patients were being seen frequently and antipsychotic treatment was optimized. Randomized, controlled clinical trials examining adjunctive use of antidepressants, anxiolytics and sedative/hypnotics to target symptoms of anxiety, depression, and insomnia in patients with schizophrenia are needed to adequately address the efficacy of these interventions. PMID- 21983498 TI - Antipsychotics and physical attractiveness. AB - BACKGROUND: Antipsychotics are effective in treating the symptoms of schizophrenia, but they may induce adverse effects, some of which-those that impact negatively on physical appearance-have not been sufficiently discussed in the psychiatric literature. AIM: Through a narrative review, to catalog antipsychotic side effects that interfere with physical attractiveness and to suggest ways of addressing them. METHOD: PubMed databases were searched for information on the association between "antipsychotic side effects" and "attractiveness" using those two search phrases plus the following terms: "weight," "teeth," "skin," "hair," "eyes," "gait," "voice," "odor." Data from relevant qualitative and quantitative articles were considered, contextualized, and summarized. RESULTS: Antipsychotics, as a group, increase weight and may lead to dry mouth and bad breath, cataracts, hirsutism, acne, and voice changes; they may disturb symmetry of gait and heighten the risk for tics and spasms and incontinence, potentially undermining a person's attractiveness. CONCLUSIONS: Clinicians need to be aware of the impact of therapeutic drugs on appearance and how important this issue is to patients. Early in treatment, they need to plan preventive and therapeutic strategies. PMID- 21983499 TI - The comorbidity of psychotic symptoms and posttraumatic stress disorder: evidence for a specifier in DSM-5. AB - The comorbidity of posttraumatic stress disorder (PTSD) and psychotic symptoms is higher than what might be expected based on the prevalence of either disorder alone. Furthermore, the presence of psychotic symptoms is evident in PTSD patients who do not otherwise meet criteria for a psychotic spectrum disorder. The current paper discusses three existing hypotheses regarding the relation of PTSD and psychosis and presents a series of case studies that illustrates this phenomenon across a diverse group of patients and scenarios. Clinical implications in light of these case studies are offered, including the suggestion that the next edition of the Diagnostic and Statistical Manual of Mental Disorders includes a specifier of PTSD with psychotic features. PMID- 21983500 TI - Psychosis risk syndrome and DSM-5: time for a dimensional approach to at-risk mental states? AB - The development of formal, empirically grounded methods for assessing At-Risk Mental States (ARMS) is becoming prominent, especially in light of the eventual inclusion of a pertinent "Psychosis risk syndrome" category in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Indeed, the phenomenology of risk syndromes for psychosis is complex, nuanced and clinically overlapping with multifarious transitory mental states. Supplementing current prodromal/Ultra-High Risk (UHR) criteria with a dimensional psychopathological approach would favor a rational mapping of emergent needs in ARMS help seekers and provide a more fine-grained reference framework for patient-centered risk stratification and intervention. PMID- 21983501 TI - Infection-associated clozapine toxicity. AB - Three case vignettes are presented documenting the rise in serum clozapine that occurred at a time of acute infection in these patients. The literature on this phenomenon is scant. The physiological processes that occur in the acute phase of the inflammatory response are summarized and provide an explanation of how clozapine levels may rise in response to infection. The risk of clozapine toxicity occurring in association with infections is highlighted. PMID- 21983502 TI - Carbon monoxide poisoning: case studies and review. AB - This article describes carbon monoxide poisoning. Using a case study approach, the article covers pathophysiology, epidemiology, clinical presentation, and complications. A nursing care plan is presented to guide the critical care nurse in the care of patients in this type of condition. PMID- 21983504 TI - Preventing intensive care unit delirium: a patient-centered approach to reducing sleep disruption. AB - Delirium in the intensive care unit is a disorder with multifactorial causes and is associated with poor outcomes. Sleep-wake disturbance is a common experience for patients with delirium. Care processes that disrupt sleep can lead to sleep deprivation, contributing to delirium. Patient-centered care is a concept that considers what is best for each individual. How can clinicians use a patient centered approach to alter processes to decrease patient disruptions and improve sleep and rest? Could timing of blood draws and soothing music work to promote sleep? PMID- 21983506 TI - The rapid response team nurse's role in end-of-life discussions during critical situations. AB - Rapid response teams have been in existence in hospitals over the past decade. This team call may offer life-saving interventions that save lives but, in some cases, may prolong the dying process. There are times in which the rapid response team nurse and the intensive care nurses need to have an understanding of the families' perception of what is occurring and manage this situation through communication, empathy, and information sharing. The nurse must be involved during discussions surrounding end-of-life decisions. The nurse also has a role in supporting the family through this difficult time of making a decision to withhold life-supporting measures. PMID- 21983507 TI - Goal of the day: initiating goal of the day to improve patient- and family centered care. AB - Goal of the day is a current topic of interest in helping to provide patient- and family-centered care, increase their satisfaction, and improve patient outcomes. Despite advancements in health care and provision of evidence-based care, we often fail to meet a patient's other needs. These needs are related to personalizing care by taking evidence-based standards of care and incorporating the patient's desires and goals. To deliver patient- and family-centered care, we need to demonstrate respect for the patient and family, build trust, and integrate their desires and goals into the daily care plan. The purpose of this project was to institute a goal of the day, increase patient and family satisfaction, and monitor outcomes. PMID- 21983508 TI - Changes in myocardial infarction-specific sexual counseling by cardiac nurses. AB - It is largely unknown if changes in the practice of sexual counseling of myocardial infarction (MI) patients by cardiac nurses have occurred over time. Therefore, the purpose of this study was to examine changes in the practice of MI specific sexual counseling by cardiac nurses, comparing the years 1994 and 2009. Based on these results, suggestions for sexual counseling of MI patients are provided. PMID- 21983510 TI - Moral distress, compassion fatigue, and perceptions about medication errors in certified critical care nurses. AB - The primary purpose of this study was to examine the previously untested relationships between moral distress, compassion fatigue, perceptions about medication errors, and nurse characteristics in a national sample of 205 certified critical care nurses. In addition, this study included a qualitative exploration of the phenomenon of medication errors in a smaller subset of certified critical care nurses. Results revealed statistically significant correlations between moral distress, compassion fatigue, and perceptions about medication errors in this group. Implications for critical care nurses seeking to create work environments conducive to the reduction of medication errors are explored. PMID- 21983512 TI - Evidence-based practice strategy: increasing timely nutrition in mechanically ventilated trauma surgical patients. AB - Malnutrition is common in the intensive care unit (ICU) and is related to higher incidence of morbidity and mortality among seriously ill patients. Achieving a quality nutritional care plan is a challenge to critical care practitioners and dietitians worldwide. The multifaceted and advanced therapies in the ICU historically take priority over nutritional assessments and interventions and may cause delay in achieving quality nutritional care. The initiation of nutrition in mechanically ventilated adult trauma patients is inconsistent in some hospitals. The implementation plan in this early nutrition project involved an algorithm, physicians order set, and nurse advocacy plan. Early nutritional support will likely be associated with improved clinical outcomes. PMID- 21983518 TI - A guest editorial: and a bit of comic relief. PMID- 21983522 TI - Posterior motion preserving implants evaluated by means of intervertebral disc bulging and annular fiber strains. AB - BACKGROUND: The aims of motion preserving implants are to ensure sufficient stability to the spine, to release facet joints by also allowing a physiological loading to the intervertebral disc. The aim of this study was to assess disc load contribution by means of annular fiber strains and disc bulging of intact and stiffened segments. This was compared to the segments treated with various motion preserving implants. METHODS: A laser scanning device was used to obtain three dimensional disc bulging and annular fiber strains of six lumbar intervertebral discs (L2-3). Specimens were loaded with 500N or 7.5Nm moments in a spine tester. Each specimen was treated with four different implants; DSSTM, internal fixator, CoflexTM, and TOPSTM. FINDINGS: In axial compression, all implants performed in a similar way. In flexion, the Coflex decreased range of motion by 13%, whereas bulging and fiber strains were similar to intact. The DSS stabilized segments by 54% compared to intact. TOPS showed a slight decrease in fiber strains (5%) with a range of motion similar to intact. The rigid fixator allowed strains up to 2%. In lateral bending, TOPS yielded range of motion values similar to intact, but maximum fiber strains doubled from 6.5% (intact) to 13.8%. Coflex showed range of motion, bulging and strain values similar to intact. The DSS and the rigid fixator reduced these values. The implants produced only minor changes in axial rotation. INTERPRETATION: This study introduces an in vitro method, which was employed to evaluate spinal implants other than standard biomechanical methods. We could demonstrate that dynamic stabilization methods are able to keep fiber strains and disc bulging in a physiological range. PMID- 21983521 TI - Efficacy of genetically modified Bt toxins against insects with different genetic mechanisms of resistance. AB - Transgenic crops that produce Bacillus thuringiensis (Bt) toxins are grown widely for pest control, but insect adaptation can reduce their efficacy. The genetically modified Bt toxins Cry1AbMod and Cry1AcMod were designed to counter insect resistance to native Bt toxins Cry1Ab and Cry1Ac. Previous results suggested that the modified toxins would be effective only if resistance was linked with mutations in genes encoding toxin-binding cadherin proteins. Here we report evidence from five major crop pests refuting this hypothesis. Relative to native toxins, the potency of modified toxins was >350-fold higher against resistant strains of Plutella xylostella and Ostrinia nubilalis in which resistance was not linked with cadherin mutations. Conversely, the modified toxins provided little or no advantage against some resistant strains of three other pests with altered cadherin. Independent of the presence of cadherin mutations, the relative potency of the modified toxins was generally higher against the most resistant strains. PMID- 21983523 TI - Potential candidate genomic biomarkers of drug induced vascular injury in the rat. AB - Drug-induced vascular injury is frequently observed in rats but the relevance and translation to humans present a hurdle for drug development. Numerous structurally diverse pharmacologic agents have been shown to induce mesenteric arterial medial necrosis in rats, but no consistent biomarkers have been identified. To address this need, a novel strategy was developed in rats to identify genes associated with the development of drug-induced mesenteric arterial medial necrosis. Separate groups (n=6/group) of male rats were given 28 different toxicants (30 different treatments) for 1 or 4 days with each toxicant given at 3 different doses (low, mid and high) plus corresponding vehicle (912 total rats). Mesentery was collected, frozen and endothelial and vascular smooth muscle cells were microdissected from each artery. RNA was isolated, amplified and Affymetrix GeneChip(r) analysis was performed on selectively enriched samples and a novel panel of genes representing those which showed a dose responsive pattern for all treatments in which mesenteric arterial medial necrosis was histologically observed, was developed and verified in individual endothelial cell- and vascular smooth muscle cell-enriched samples. Data were confirmed in samples containing mesentery using quantitative real-time RT-PCR (TaqManTM) gene expression profiling. In addition, the performance of the panel was also confirmed using similarly collected samples obtained from a timecourse study in rats given a well established vascular toxicant (Fenoldopam). Although further validation is still required, a novel gene panel has been developed that represents a strategic opportunity that can potentially be used to help predict the occurrence of drug-induced mesenteric arterial medial necrosis in rats at an early stage in drug development. PMID- 21983520 TI - Therapeutic siRNA silencing in inflammatory monocytes in mice. AB - Excessive and prolonged activity of inflammatory monocytes is a hallmark of many diseases with an inflammatory component. In such conditions, precise targeting of these cells could be therapeutically beneficial while sparing many essential functions of the innate immune system, thus limiting unwanted effects. Inflammatory monocytes-but not the noninflammatory subset-depend on the chemokine receptor CCR2 for localization to injured tissue. Here we present an optimized lipid nanoparticle and a CCR2-silencing short interfering RNA that, when administered systemically in mice, show rapid blood clearance, accumulate in spleen and bone marrow, and localize to monocytes. Efficient degradation of CCR2 mRNA in monocytes prevents their accumulation in sites of inflammation. Specifically, the treatment attenuates their number in atherosclerotic plaques, reduces infarct size after coronary artery occlusion, prolongs normoglycemia in diabetic mice after pancreatic islet transplantation, and results in reduced tumor volumes and lower numbers of tumor-associated macrophages. PMID- 21983524 TI - Hypertonicity activates pulmonary vagal afferents independently of vasoconstriction. AB - Injecting hypertonic saline into the lung periphery causes a vagally mediated neural hyperpnea and tachypnea (the excitatory lung reflex, ELR). In the present study, we tested the hypothesis that hypertonic saline activates lung afferents mainly by increasing fluid flux from pulmonary vessels into the alveoli. If our hypothesis is correct, reducing perfusion of the vagal sensory region will reduce the fluid flux and attenuate the ELR. In anesthetized, open chest and mechanically ventilated rabbits, using intravital video microscopy, we confirmed that topical KCl (100 mM) constricted sub-pleural blood vessels and limited blood flow significantly, as indicated by a 43.3+/-9% decrease in arteriolar diameters (p<0.005), sluggish microvascular flow and paleness of alveolar walls. Then, we compared respiratory responses (assessed from phrenic nerve activity) to injections of hypertonic saline (8.1%, 0.1 ml) into the lung periphery before and after locally injecting KCl to limit fluid flux. The respiratory responses were the same with or without vasoconstriction. However, the responses were significantly decreased (from 22+/-5% to 1+/-2% for phrenic amplitude and from 75+/-9% to 13+/-6% for phrenic burst rate; n=14, p<0.02) after local injection of 2% lidocaine to block sensory endings. Since the ELR was not attenuated by vasoconstriction, increased transvascular fluid flux does not appear to be a major mechanism for hypertonic saline induced ELR. PMID- 21983526 TI - Reservoirs of Cyprinid herpesvirus 3 (CyHV-3) DNA in sediments of natural lakes and ponds. AB - Cyprinid herpesvirus 3 (CyHV-3) is a lethal DNA virus that infects common carp and koi. It has caused outbreak of the disease within both aquaculture and natural environmental ecosystems. However, there is not enough understanding of the distribution of CyHV-3 in the natural environments, partly because there is no suitable quantification method. In this study, we tested CyHV-3 extraction methods from sediment and then compared its abundance between sediment and water using real-time PCR. Sediment samples were taken from lake and pond, and total viral DNA was extracted using the viral elution method recommended by the US Environmental Protection Agency (manual method), as well as a commercial DNA extraction kit for soil (commercial kit method) before PCR detection. 7 of 12 (58%) and 5 of 10 (50%) sediment samples showed PCR positive signal for CyHV-3 DNA using the manual method and the commercial kit, respectively, and consistent results were obtained from the samples using the manual method between two independent primer sets. The quantification of CyHV-3 DNA in natural sediment using the manual method and external standard virus revealed that its concentration was 1.2*10(4) to 3.3*10(5) copies DNA/kg. The concentration in sediments was 46-1238 times higher than that in water from the same location, suggesting that sediment could act as a reservoir for CyHV-3 in natural freshwater environments. This is the first report of the existence of CyHV-3 in the sediment of a natural lake or pond. PMID- 21983525 TI - Response functions for computing absorbed dose to skeletal tissues from neutron irradiation. AB - Spongiosa in the adult human skeleton consists of three tissues-active marrow (AM), inactive marrow (IM) and trabecularized mineral bone (TB). AM is considered to be the target tissue for assessment of both long-term leukemia risk and acute marrow toxicity following radiation exposure. The total shallow marrow (TM(50)), defined as all tissues lying within the first 50 um of the bone surfaces, is considered to be the radiation target tissue of relevance for radiogenic bone cancer induction. For irradiation by sources external to the body, kerma to homogeneous spongiosa has been used as a surrogate for absorbed dose to both of these tissues, as direct dose calculations are not possible using computational phantoms with homogenized spongiosa. Recent micro-CT imaging of a 40 year old male cadaver has allowed for the accurate modeling of the fine microscopic structure of spongiosa in many regions of the adult skeleton (Hough et al 2011 Phys. Med. Biol. 56 2309-46). This microstructure, along with associated masses and tissue compositions, was used to compute specific absorbed fraction (SAF) values for protons originating in axial and appendicular bone sites (Jokisch et al 2011 Phys. Med. Biol. 56 6857-72). These proton SAFs, bone masses, tissue compositions and proton production cross sections, were subsequently used to construct neutron dose-response functions (DRFs) for both AM and TM(50) targets in each bone of the reference adult male. Kerma conditions were assumed for other resultant charged particles. For comparison, AM, TM(50) and spongiosa kerma coefficients were also calculated. At low incident neutron energies, AM kerma coefficients for neutrons correlate well with values of the AM DRF, while total marrow (TM) kerma coefficients correlate well with values of the TM(50) DRF. At high incident neutron energies, all kerma coefficients and DRFs tend to converge as charged-particle equilibrium is established across the bone site. In the range of 10 eV to 100 MeV, substantial differences are observed among the kerma coefficients and DRF. As a result, it is recommended that the AM kerma coefficient be used to estimate the AM DRF, and that the TM kerma coefficient be used to estimate the TM(50) DRF below 10 eV. Between 10 eV and 100 MeV, the appropriate DRF should be used as presented in this study. Above 100 MeV, spongiosa kerma coefficients apply well for estimating skeletal tissue doses. DRF values for each bone site as a function of energy are provided in an electronic annex to this article available at http://stacks.iop.org/0031 9155/56/6873/mmedia. PMID- 21983527 TI - [Surgical treatment of the unformed intestinal fistulae]. AB - Treatment results of 5 patients with unformed intestinal fistulae are represented. High unformed intestinal fistulae are acknowledged to be completely unsuitable for conservative treatment and should be operated on. Complex treatment should include complete parenteral feeding, adequate fecal diversion with the use of aspirational drainage. Surgical treatment must be y the increase of fistula discharge or absence of fistula formation. Low intestinal fistulae should better be surgically dissected after their organization, otherwise urgent surgery is to be performed by complications development, such as purulent leakage into the abdominal cavity or severe wound infection. PMID- 21983528 TI - [Surgical treatment of the aortic dissection type B: analysis of 15 years' experience]. AB - 65 patients with the aortic dissection type B were operated on in the period 1995 2010. The proximal local aortic prosthetics proved to be the method of choice in treatment of such patients. The method allowed the reduction of the hospital lethality on 5,7 +/- 3,9% and considerably decrease the overall hospital stay. PMID- 21983529 TI - [The autovenous by-pass by distal arterial occlusion of lower limbs in patients with diabetes mellitus]. AB - Results of the autovenous by-pass in situ by distal combined arterial occlusion of femoral-popliteal and ankle arterial segments were analyzed. The main group consisted of 43 patients with diabetes mellitus and lower limbs ischemia grade IV in 81,4%. The comparison group consisted of 77 patients without diabetes and critical lower limbs ischemia in 84,4%. The 30 days by-pass patency was 90,5% in diabetic patients; whereas in the absence of diabetes mellitus the patency rate was 89%. There were no significant difference between two groups within the 2 years following the operation. After 3 postoperative years patients with diabetes showed poorer results: cumulative by-pass patency was 45,4%, limb preservation rate was 58,7%, whereas the relevant rates in the control group were 49,6 and 87,9%, respectively. The hemodynamic features of the by-pass make it suitable for the patients with diabetes mellitus and arterial occlusion by the diabetic foot syndrome. PMID- 21983530 TI - [Clinico-morphological aspects of diagnostics and treatment of the surgical sepsis]. AB - Treatment results of 63 patients with surgical sepsis (aged 17-92 years) were analyzed. The necessity of intravenous immunoglobulin infusion in the complex treatment of sepsis was proved by the comparative morphological study of immunocompetent tissues of 30 patients, died of sepsis and nonseptic reasons. The rational use of intravenous immunoglobulin should be based on the condition of the patient and defined by the APACHE II and SOFA scores. PMID- 21983531 TI - [The use of exogenous nitrogen monoxide for the prophylaxis of postoperative wound infection]. AB - The study covers treatment results of 220 patients operated on ventral hernia and in vivo experimental treatment of 36 rats proved the nitrogen monoxide (NO) to be the effective means of wound infection prophylaxis. NO potentiates antiseptic effects, minimizing intraoperative wound contamination. It, besides, stimulates endothelial and basal cells of epidermis proliferation. Wound infection was observed only in 9,8% of patients, treated with NO intraoperatively. All cases of infective complications were serous and infiltrative, but not purulent. PMID- 21983532 TI - [The radical minimal access thoracoplasty by funnel chest in adults]. AB - A new technique of radical thoracoplasty, performed with a small size incision, using the sternocostal complex fixation with nitinol plates with shape memory and the surgical toolkit required for the purpose, has been successfully introduced. 23 patients underwent surgery using the technique. Tree patients had early postoperative complications: 2 cases of exudative pleurisy and 1 case of bronchitis aggravation. Good cosmetic results was achieved in all operated patients. The mechanical ground of the technique is based on the use of the effective force of the sternum traction and the pressure of the plate on the tissues below. The main advantage of the method is avoidance of the transverse sternotomy. PMID- 21983533 TI - [The efficacy of hand desimpatization after sympatectomy by complex regional pain syndrome]. AB - 64 patients operated on the reason of complex regional hand pain syndrome were examined with the use of laser spectral Doppler flowmetry and thermography. 33 patients had thoracoscopic Th3 ganglion clipation; 16 patients had brachial artery and vein perivascular sympathectomy; 15 patients periarterial sympathectomy on the level of brachial artery. Desympathisation (microcirculatory hemodynamic improvement and trophotropic microcirculation regulatory changes) was mostly apparent after thoracoscopic clipation and perivascular desympatisation in comparison with isolated periarterial sympatectomy. PMID- 21983534 TI - [The transosseous osteosynthesis by intra- and periarticular fractures of the knee joint]. AB - 105 patients with intra- and periarticular fractures of the knee joint were operated on with the use of nail and spin-nail apparatus constructed by A.I. Gorodnichenko. The possibility of atraumatic closed bone fragments fixation allowed quick patients' activization, and, as follows, improved their life quality, decreased the hospital stay and minimized complication rate. Fracture consolidation was achieved in all cases, the only complication registered was skin inflammation around the nail in 5 patients. PMID- 21983535 TI - [The use of ozone and low-intensive laser irradiation in complex treatment of complicated duodenal ulcer]. AB - The study is based on the examination of 12 patients with perforative duodenal ulcer and 24 patients operated on recurrent bleeding duodenal ulcer. Some component of the immune system, such as T- and B-lymphocytes rates, immunoglobulin rate and macrophagal activity, were decreased prior the beginning of the complex treatment. Normalisation of humoral and cell immunity was registered on 10-12 days after the beginning of the ozone and low-intensive laser irradiation. PMID- 21983536 TI - [The use of laser beam irradiation by the acute destructive pancreatitis]. AB - The use of intravenous laser blood irradiation and transcutaneous laserotherpy together with mini-invasive and endoscopic surgical procedures permit to avoid infection of pancreatic lesions in 67.7%. Lethality rate by sterile pancreonecrosis decreased from 24.4 to 5.1%. The complex use of laser, antioxidant and antibacterial therapy decreased the lethality rate by the infected pancreonecrosis from 42.8 to 23.1%. PMID- 21983537 TI - [The role of surgical access in postoperative ventral hernia development]. AB - Long-term follow-up of 508 patients after various surgical procedures has been conducted. Of the 351 patients were operated on using a paramedian incision, 109 had an upper median laparotomy and the rest 48 had an oblique subcostal incision. Post-operative ventral hernias were registered in 45 (8.86%) patients. The upper median laparotomy herniated in 18 (16.51%) patients, paramedian incision - in 17 (4.84%), and the oblique subcostal incision herniated in 10 (20.83%). Hernia was noticed by the patient within 12 months after the initial operation in 46.67%, of them in 85.71% - within first 6 months. 53,33% of patients were diagnosed with postoperative hernia only after thorough examination. Thus, paramedian incision is considered to be the most preferable access. Postoperative hernias develop within the first 6-12 months postoperatively, later hernia registration is a result of poor examination. PMID- 21983538 TI - [Method of local treatment of trophic ulcers of venous etiology]. AB - The study is based on the results of local treatment of trophic ulcers of 150 patients with chronic venous insufficiency of the lower extremities. Local treatment is laser treatment and diagnostic unit with a wavelength lambda=0,65 mkm and output power of 30 mW in pulsed mode for 10 minutes 1 times per day for 7 10 days. As an objective criterion for determining the speed and intensity of the healing of trophic ulcers and non-contact fixing their area of applied computer thermography. True healing of ulcers was achieved in all patients during the period from 14 to 28 days. PMID- 21983539 TI - [Salmonella as an etiological agent of hematogenous ostheomyelitis in adults]. PMID- 21983540 TI - Use of tranexamic acid to reduce bleeding in burns surgery. AB - We describe, for the first time, the use of topical tranexamic acid as an adjunct to traditional methods in the control of bleeding in burns surgery. We illustrate our use with a case example and continue to discuss the reasons we believe it is a useful, effective and safe means of achieving haemostasis. PMID- 21983541 TI - Crystal structure and role of glycans and dimerization in folding of neuronal leucine-rich repeat protein AMIGO-1. AB - AMIGO-1 is the parent member of a novel family of three cell surface leucine-rich repeat (LRR) proteins. Its expression is induced by the binding of HMGB1 (high mobility group box 1 protein) to RAGE (receptor for advanced glycation end products) on neurons. Binding of HMGB1 to RAGE is known to have a direct effect on cellular growth regulation and mobility, and AMIGO-1 directly supports growth of neuronal processes and fasciculation of neurites. In addition, the second member of the AMIGO-family, AMIGO-2, has been implicated in adhesion of tumor cells in adenocarcinoma and survival of neurons. We have determined the crystal structure of AMIGO-1 at 2.0 A resolution, which reveals a typical cell surface LRR domain arrangement with N- and C-terminal capping domains with disulfide bridges, followed by a C2-type Ig domain. AMIGO-1 is a dimer, with the LRR regions forming the dimer interface, and sequence conservation analysis and static light-scattering measurements suggest that all three AMIGO family proteins form similar dimers. Based on the AMIGO-1 structure, we have also modeled AMIGO-2 and present small-angle X-ray scattering data on AMIGO-2 and AMIGO-3. Our mutagenesis studies show that AMIGO-1 dimerization is necessary for proper cell surface expression and thus probably for proper or stable folding in the endoplastic reticulum and for the function of the protein. Based on the data presented earlier, we also suggest that dimerization through the LRR-LRR interface is likely to be involved in cell-cell adhesion by AMIGO-1, while extensive glycosylation may have a role. PMID- 21983542 TI - Unraveling framework of the ancestral Mediator complex in human diseases. AB - Mediator (MED) is a fundamental component of the RNA polymerase II-mediated transcription machinery. This multiprotein complex plays a pivotal role in the regulation of eukaryotic mRNA synthesis. The yeast Mediator complex consists of 26 different subunits. Recent studies indicate additional pathogenic roles for Mediator, for example during transcription elongation and non-coding RNA production. Mediator subunits have been emerging also to have pathophysiological roles suggesting MED-dependent therapeutic targets involving in several diseases, such as cancer, cardiovascular disease (CVD), metabolic and neurological disorders. PMID- 21983544 TI - Anchoring of bacterial effectors to host membranes through host-mediated lipidation by prenylation: a common paradigm. AB - Post-translational lipidation by prenylation of the CaaX-box C-terminal motif in eukaryotic proteins facilitates anchoring of hydrophilic proteins, such as Ras and Rab, to membranes. A large cadre of bacterial effectors injected into host cells is anchored to host membranes by unknown mechanisms. As already documented for Legionella and Salmonella, we propose a common paradigm of microbial exploitation of the host prenylation machinery for anchoring of injected effectors to host membranes. This is supported by numerous potential microbial CaaX-box-containing proteins identified using refined bioinformatic tools. We also propose utilization of the CaaX motif as a membrane-targeting tag for proteins expressed in eukaryotic cells to facilitate deciphering of biological function. PMID- 21983543 TI - Interaction between NF-kappaB signaling and Notch signaling in gliogenesis of mouse mesencephalic neural crest cells. AB - In the present study, we elucidated that nuclear factor-kappaB (NF-kappaB) participates in the gliogenic specification of mouse mesencephalic neural crest cells. Whereas transfection of the NF-kappaB expression vector stimulated gliogenesis, treatment with the dominant negative NF-kappaB expression vector or NF-kappaB small interfering RNA suppressed the promotion of gliogenic specification by FGF treatment or Notch activation. This suppression was recovered by the treatment with the Deltex-1 expression vector or mammalian hairy and enhancer of split homologs expression vectors. Furthermore, transfection of the inhibitor of kappaB (IkappaB) expression vector inhibited gliogenesis. In addition, treatment with the NF-kappaB expression vector promoted the expression of Deltex-1. These data suggest that NF-kappaB signaling is implicated in the gliogenesis through the interaction with Notch signaling. Moreover, cells that contain Sox10 expressed NF-kappaB and Deltex-1 in the presumptive trigeminal ganglia of embryonic day 9.0-9.5 mouse embryos. This observation supports our notion that the interaction between NF-kappaB signaling and Notch signaling plays an important role in the gliogenic specification of mouse mesencephalic neural crest cells. PMID- 21983545 TI - A workflow learning model to improve geovisual analytics utility. AB - INTRODUCTION: This paper describes the design and implementation of the G-EX Portal Learn Module, a web-based, geocollaborative application for organizing and distributing digital learning artifacts. G-EX falls into the broader context of geovisual analytics, a new research area with the goal of supporting visually mediated reasoning about large, multivariate, spatiotemporal information. Because this information is unprecedented in amount and complexity, GIScientists are tasked with the development of new tools and techniques to make sense of it. Our research addresses the challenge of implementing these geovisual analytics tools and techniques in a useful manner. OBJECTIVES: The objective of this paper is to develop and implement a method for improving the utility of geovisual analytics software. The success of software is measured by its usability (i.e., how easy the software is to use?) and utility (i.e., how useful the software is). The usability and utility of software can be improved by refining the software, increasing user knowledge about the software, or both. It is difficult to achieve transparent usability (i.e., software that is immediately usable without training) of geovisual analytics software because of the inherent complexity of the included tools and techniques. In these situations, improving user knowledge about the software through the provision of learning artifacts is as important, if not more so, than iterative refinement of the software itself. Therefore, our approach to improving utility is focused on educating the user. METHODOLOGY: The research reported here was completed in two steps. First, we developed a model for learning about geovisual analytics software. Many existing digital learning models assist only with use of the software to complete a specific task and provide limited assistance with its actual application. To move beyond task oriented learning about software use, we propose a process-oriented approach to learning based on the concept of scientific workflows. Second, we implemented an interface in the G-EX Portal Learn Module to demonstrate the workflow learning model. The workflow interface allows users to drag learning artifacts uploaded to the G-EX Portal onto a central whiteboard and then annotate the workflow using text and drawing tools. Once completed, users can visit the assembled workflow to get an idea of the kind, number, and scale of analysis steps, view individual learning artifacts associated with each node in the workflow, and ask questions about the overall workflow or individual learning artifacts through the associated forums. An example learning workflow in the domain of epidemiology is provided to demonstrate the effectiveness of the approach. RESULTS/CONCLUSIONS: In the context of geovisual analytics, GIScientists are not only responsible for developing software to facilitate visually-mediated reasoning about large and complex spatiotemporal information, but also for ensuring that this software works. The workflow learning model discussed in this paper and demonstrated in the G-EX Portal Learn Module is one approach to improving the utility of geovisual analytics software. While development of the G-EX Portal Learn Module is ongoing, we expect to release the G-EX Portal Learn Module by Summer 2009. PMID- 21983546 TI - Insect cells as factories for biomanufacturing. AB - Insect cells (IC) and particularly lepidopteran cells are an attractive alternative to mammalian cells for biomanufacturing. Insect cell culture, coupled with the lytic expression capacity of baculovirus expression vector systems (BEVS), constitutes a powerful platform, IC-BEVS, for the abundant and versatile formation of heterologous gene products, including proteins, vaccines and vectors for gene therapy. Such products can be manufactured on a large scale thanks to the development of efficient and scaleable production processes involving the integration of a cell growth stage and a stage of cell infection with the recombinant baculovirus vector. Insect cells can produce multimeric proteins functionally equivalent to the natural ones and engineered vectors can be used for efficient expression. Insect cells can be cultivated easily in serum- and protein-free media. A growing number of companies are currently developing an interest in producing therapeutics using IC-BEVS, and many products are today in clinical trials and on the market for veterinary and human applications. This review summarizes current knowledge on insect cell metabolism, culture conditions and applications. PMID- 21983547 TI - Severe epithelial edema in Clearkone SynergEyes contact lens wear for keratoconus. AB - OBJECTIVE: The aim was to report three cases of severe bilateral epithelial edema (central corneal clouding [CCC]) in association with ClearKone SynergEyes hybrid contact lenses for the vision rehabilitation of keratoconus. METHODS: Retrospective case series of six eyes of three patients that developed CCC with ClearKone SynergEyes hybrid contact lens wear shortly after beginning to wear those lenses. RESULTS: Severe CCC was diagnosed on removal of the lenses. Despite attempts to modify the parameters of the lenses to reduce edema, two patients discontinued lens wear entirely, and one patient was able to wear lenses only on a limited basis. CONCLUSIONS: Different degrees of CCC have been reported with the use of polymethyl methacrylate lenses; however, the condition may also occur with the use of ClearKone SynergEyes lenses. Although the lenses may provide good subjective responses, careful observation of the corneal response after 5 hrs of wear is advised. PMID- 21983548 TI - Topographic paracentral corneal thickness with pentacam and orbscan: effect of acoustic factor. AB - PURPOSE: To evaluate the effect of an acoustic factor (AF) on the comparison of central corneal thickness (CCT) and peripheral corneal thickness (PCT) measurements with Orbscan II and Pentacam. METHODS: The CCT and PCT at 1, 2, and 3 radial distances from the corneal apex were measured using Orbscan II and Pentacam in 22 right eyes of 22 healthy adults (7 men, 15 women). Three measures were obtained from each 1 of the 25 points measured and then compared to gauge the agreement between both devices at the corneal center and anular areas located at 1-, 2-, and 3-mm distances from the central measurement. Orbscan II readings were considered with and without an AF correction. RESULTS: Pentacam provides statistically significant higher values than Orbscan II does at all the 25 locations analyzed (P<0.001). With a few exceptions, the average difference was fairly constant between 20 and 40 MUm for all the corneal locations. A high correlation existed between central readings (r(2)=0.927; P<0.001) and average thickness at each one of the annular areas being analyzed (r(2)=0.897 at 1 mm, r(2)=0.876 at 2 mm, and r(2)=0.870 at 3 mm); Pentacam minus Orbscan II value averaged for all the points changed from -28+/-10 to -22+/-9 MUm after the removal of the AF in Orbscan II. CONCLUSIONS: Central and peripheral measurements of the corneal thickness obtained with Orbscan II and Pentacam are significantly different. The removal of the AF in Orbscan II renders lower mean differences but decreases the agreement between both systems and potentially induces an overestimation of CCT and PCT by Orbsan II compared with Pentacam. PMID- 21983549 TI - Anterior and posterior corneal elevation after orthokeratology and standard and customized LASIK surgery. AB - PURPOSE: To quantify the changes in the elevation topography of the front and back corneal surfaces after three different refractive treatments for correcting myopia with standard and custom laser in situ keratomileusis (LASIK) and orthokeratology using corneal refractive therapy. METHODS: We evaluated 20 eyes undergoing orthokeratology for correction of myopia spherical equivalent (mean+/ SD=-3.41+/-0.76 D), 18 eyes undergoing custom LASIK surgery (mean+/-SD=-4.14+/ 0.89 D), and 23 eyes undergoing standard LASIK (mean+/-SD=-3.61+/-0.67 D). The values of front and back corneal surfaces were derived by using Pentacam (Oculus, Inc. GmbH, Wetzlar, Germany) before and at least 3 months after each treatment, in the center of the cornea and 4 points to each side of the horizontal meridian at intervals of 1 mm. RESULTS: Corneal elevation data before treatment were not statistically different between patients in either group (P>0.070, for back and front elevation). After treatment, both surgical procedures significantly increased the positive value of the front elevation beyond an area of 6 mm. The opposite trend was found within the central 5 mm of the cornea, presenting a statistically significant decrease in elevation (P<0.001). In the case of orthokeratology, the elevation experienced a minor but a statistically significant reduction in the central region (P<0.001). On the back surface, the elevation did not undergo statistically significant alterations in any of the procedures and none of the items discussed (P>0.285). CONCLUSIONS: Differences in front corneal elevation changes between LASIK and orthokeratology reveal a much different mechanism for producing corneal power subtraction. The back corneal surface does not suffer significant changes after surgical and nonsurgical treatments for the correction of myopia. PMID- 21983550 TI - Topography-based RGP lens fitting in normal corneas: the relevance of eyelid and tear film attributes. AB - OBJECTIVES: The aim of this study was to investigate the influence of eyelid and tear film attributes on the ability of a topography-based contact lens-fitting module to correctly predict rigid gas permeable (RGP) contact lens parameters leading to successful in situ final lens fitting in normal corneas. METHODS: A total of 28 healthy eyes with spherical refraction ranging from -2.00 to -6.00 D, refractive and anterior corneal astigmatism <-0.75 D and smooth keratometric mires were fitted with diagnostic trial tricurve RGP lenses as determined through simulated fluorescein pattern analysis. Modifications in the back optic zone radius (BOZR) and total diameter (TD) were implemented to the suggested parameters until a satisfactory fit was observed, whereupon the differences from the suggested parameters were recorded. Eyelid position, upper lid tonus, blinking completeness, tear film volume, and quality and corneal eccentricity were evaluated, and their relationship with the number of required parameter modifications was explored. RESULTS: Eyelid position and tear meniscus height presented a statistically significant association with the number of parameter changes between simulated and final in situ fittings. In addition, although eyelid position influenced both BOZR (rho=0.436; P=0.020) and TD (rho=-0.398; P=0.036), tear meniscus height only prompted TD modifications (rho=0.435; P=0.021). No additional associations were discovered and, on examining the direction of the modifications, no clear tendency could be detected. CONCLUSIONS: Eyelid position and tear meniscus height attributes, not taken into consideration by topography-based lens fitting software, influence RGP lens parameter selection. PMID- 21983551 TI - Impact of cleaning regimens in silver-impregnated and hydrogen peroxide lens cases. AB - PURPOSE: Lens storage case hygiene practices are important for safe contact lens wear. However, the effectiveness of the manufacturer's direction for use and various cleaning regimens in reducing biofilm load is yet to be evaluated and compared. This in vitro study compared the effectiveness of several cleaning methods using silver-impregnated lens case and hydrogen peroxide disinfection systems. METHODS: Biofilms of Pseudomonas aeruginosa 122 and Staphylococcus aureus ATCC 6538 were grown in silver-impregnated and hydrogen peroxide lens cases. After the establishment of the biofilms, the silver-impregnated case was subjected to one of four cleaning regimens: "manufacturer's directions for use- rinsed and recapped"; "rubbed, rinsed, and recapped"; "rubbed, rinsed, and air dried"; or "rubbed, rinsed, tissue wiped, and air dried." Hydrogen peroxide cases underwent one of two regimens: "manufacturer's directions for use--rinsed with saline and air dried" or "soaked in solution for 6 hrs." The level of residual bacteria was quantified. The efficacy of each cleaning regimen was then compared. RESULTS: Mechanical rubbing and wiping of silver-impregnated cases and soaking hydrogen peroxide cases in hydrogen peroxide were the most effective treatments for reducing biofilms. Once the silver-impregnated cases were rubbed, air drying or recapping the cases did not have any significant effect on the level of the biofilm. The level of initial biofilm formation of silver-impregnated cases was significantly lower than those of polypropylene lens cases (P<0.0001). CONCLUSIONS: Rubbing and rinsing with disinfecting solution and wiping with a tissue can be considered to be effective in removing biofilms from silver impregnated lens cases. Resoaking the basket-type lens case in hydrogen peroxide between use was found to be effective in removing biofilms from these cases. PMID- 21983552 TI - Combined application of autologous serum eye drops and silicone hydrogel lenses for the treatment of persistent epithelial defects. AB - PURPOSE: We investigated the utility of a combination of autologous serum eye drops and a silicone-hydrogel (SH) lens in the treatment of persistent epithelial defects (PEDs). METHODS: Eight patients who had distinct PED conditions were treated with 50% (v/v) autologous serum eye drops in combination with silicone hydrogel contact lenses and prospectively observed. RESULTS: The pathogenesis of PEDs included Sjogren-type dry eye syndrome, graft-versus-host disease, toxic keratitis, limbal cell deficiency, superior limbic keratoconjunctivitis, and neurotrophic keratitis. The patients had PEDs for 90+/-81.76 days (range: 30-240 days). Before the initiation of the combined treatment, three patients had already been unsuccessfully treated with SH lenses, and five patients had received serum eye drops alone. The PEDs of the eight eyes healed after a treatment period of 11.8+/-4.9 days. No visible deposits were noted on the surface of any contact lens. CONCLUSIONS: These findings demonstrate that the combination of an SH lens and serum eye drops may be effective in the treatment of intractable PEDs. PMID- 21983553 TI - Maternal glutamate intake during gestation and lactation regulates adenosine A1 and A(2A) receptors in rat brain from mothers and neonates. AB - Pregnant rats were treated daily with 1 g/L of L-glutamate in their drinking water during pregnancy and/or lactation. The effect on adenosine A1 receptor (A1R) and A(2A) receptor (A(2A)R) in brains from both mothers and 15-day-old neonates was assayed using radioligand binding and real time PCR assays. Mothers receiving L-glutamate during gestation, lactation, and throughout gestation and lactation showed a significant decrease in total A1R number (water+water, 302+/ 49 fmol/mg; L-glutamate+water, 109+/-11 fmol/mg, P<0.01; water+L-glutamate, 52+/ 13 fmol/mg, P<0.01; L-glutamate+L-glutamate, 128+/-33 fmol/mg, P<0.05). No variations were detected in the Kd parameter. Concerning adenosine A(2A)R, radioligand binding assays revealed that Bmax parameter remains unaltered in maternal brain in response to glutamate exposure. However, Kd parameter was significantly decreased in all L-glutamate-treated groups (water+water, 5.3+/-1.3 nM; L-glutamate+/-water, 0.5+/-0.1 nM; water+L-glutamate, 0.9+/-0.1 nM; L glutamate+/-L-glutamate, 0.7+/-0.1 nM, P<0.01 in all cases). In both male and female neonates, A1R was also decreased after long-term glutamate exposure during gestation, lactation, and gestation plus lactation (male neonates: water+water, 564+/-68 fmol/mg; L-glutamate+water, 61+/-8 fmol/mg; water+L-glutamate, 95+/-20 fmol/mg; L-glutamate+L-glutamate, 111+/-15 fmol/mg; P<0.01 in all cases; female neonates: water+water, 216+/-35 fmol/mg; L-glutamate+water, 59+/-9 fmol/mg; water+L-glutamate, 139+/-16 fmol/mg; L-glutamate+L-glutamate, 97+/-14 fmol/mg; P<0.01 in all cases). No variations were found in mRNA level coding adenosine A(1)R in maternal or neonatal brain. Concerning adenosine A(2A)R, radioligand binding assays revealed that Bmax parameter was significantly increased in male and female neonates exposed to L-glutamate during lactation (male neonates: water+water, 214+/-23 fmol/mg; water+L-glutamate, 581+/-49 fmol/mg; P<0.01; female neonates: water+water, 51+/-10 fmol/mg; water+L-glutamate, 282+/-52 fmol/mg; P<0.05). No variations were found in mRNA level coding adenosine A(2A)R in maternal or neonatal brain. In summary, long-term L-glutamate treatment during gestation and lactation promotes a significant down-regulation of A1R in whole brain from both mother and neonates and a significant up-regulation of A(2A)R in neonates exposed to L-glutamate during lactation. PMID- 21983554 TI - An integrative model of excessive reassurance seeking and negative feedback seeking in the development and maintenance of depression. AB - Depression and interpersonal dysfunction are inextricably linked. Interpersonal behaviors in individuals with depression, specifically excessive reassurance seeking (ERS) and negative feedback seeking (NFS), have recently emerged as possible risk factors for interpersonal rejection and future depression. However, existing models integrating ERS and NFS in individuals with depression lack empirical support and fail to provide an adequate explanation for the negative social and psychological consequences that concurrent ERS and NFS create. The proposed model, based on the bias and accuracy literature in close relationships, suggests that individuals with depression desire and elicit global enhancement (through ERS) and specific verification (through NFS) from close others. This model has strong theoretical and empirical foundations and suggests that depression chronicity and interpersonal distress stem from the influence that early core-beliefs about relationships and self-views have on the seemingly adaptive combination of global enhancement and specific verification. PMID- 21983555 TI - Thiol redox proteomics seen with fluorescent eyes: the detection of cysteine oxidative modifications by fluorescence derivatization and 2-DE. AB - There is increasing evidence that several reversible oxidative post-translational modifications of protein cysteines participate in cell signalling. Specific proteomic techniques are required to identify these modifications and to study their regulation in different cell processes, that are collectively known as thiol redox proteomics. Recently, fluorescence derivatization methods have been developed that enable these post-translational modifications to be studied using proteomic workflows based on two-dimensional electrophoresis, which is a relatively accessible and affordable technique. As well as enabling a large number of samples to be processed, two-dimensional electrophoresis has the advantage that it does not rely on the intensive use of mass spectrometers. This methodology allows to "visualise" redox changes in a broad context and, although identification of the modified residues is not so straightforward, complementary derivatization can overcome this drawback. Here we review the different derivatization strategies that have been employed in these studies, comparing their advantages and potential limitations. We also review the applications and results obtained, with particular emphasis on those involving (patho)physiological stimuli, thereby showing the potential of these techniques to study the thiol redox proteome. PMID- 21983556 TI - Proteomic databases and tools to decipher post-translational modifications. AB - Post-translational modifications (PTMs) are vital cellular control mechanism, which affect protein properties, including folding, conformation, activity and consequently, their functions. As a result they play a key role in various disease conditions, including cancer and diabetes. Proteomics as a rapidly growing field has witnessed tremendous advancement during the last decade, which has led to the generation of prodigious quantity of data for various organisms' proteome. PTMs being biologically and chemically dynamic process, pose greater challenges for its study. Amidst these complexities connecting the modifications with physiological and cellular cascade of events are still very challenging. Advancement in proteomic technologies such as mass spectrometry and microarray provides HT platform to study PTMs and help to decipher role of some of the very essential biological phenomenon. To enhance our understanding of various PTMs in different organisms, and to simplify the analysis of complex PTM data, many databases, software and tools have been developed. These PTM databases and tools contain crucial information and provide a valuable resource to the research community. This article intends to provide a comprehensive overview of various PTM databases, software tools, and analyze critical information available from these resources to study PTMs in various biological organisms. PMID- 21983557 TI - PI3K/AKT/mTORC1 and MEK/ERK signaling in T-cell acute lymphoblastic leukemia: new options for targeted therapy. PMID- 21983559 TI - Molecular characterization of serotype Asia-1 foot-and-mouth disease viruses in Pakistan and Afghanistan; emergence of a new genetic Group and evidence for a novel recombinant virus. AB - Foot-and-mouth disease (FMD) is endemic in Pakistan and Afghanistan. The FMD virus serotypes O, A and Asia-1 are responsible for the outbreaks in these countries. Diverse strains of FMDV, even within the same serotype, co-circulate. Characterization of the viruses in circulation can facilitate appropriate vaccine selection and tracing of outbreaks. The present study characterized foot-and mouth disease serotype Asia-1 viruses circulating in Pakistan and Afghanistan during the period 1998-2009. Phylogenetic analysis of FMDV type Asia-1 revealed that three different genetic Groups of serotype Asia-1 have circulated in Pakistan during this time. These are Group-II, -VI and, recently, a novel Group (designated here as Group-VII). This new Group has not been detected in neighbouring Afghanistan during the study period but viruses from Groups I and II are in circulation there. Using near complete genome sequences, from FMD viruses of serotypes Asia-1 and A that are currently circulating in Pakistan, we have identified an interserotypic recombinant virus, which has the VP2-VP3-VP1-2A coding sequences derived from a Group-VII Asia-1 virus and the remainder of the genome from a serotype A virus of the A-Iran05(AFG-07) sub-lineage. The Asia-1 FMDVs currently circulating in Pakistan and Afghanistan are not efficiently neutralized by antisera raised against the Asia-1/Shamir vaccine strain. Thus, new Asia-1 vaccine strains may be required to block the spread of the current Asia-1 viruses. PMID- 21983558 TI - PET image reconstruction with anatomical edge guided level set prior. AB - Acquiring both anatomical and functional images during one scan, PET/CT systems improve the ability to detect and localize abnormal uptakes. In addition, CT images provide anatomical boundary information that can be used to regularize positron emission tomography (PET) images. Here we propose a new approach to maximum a posteriori reconstruction of PET images with a level set prior guided by anatomical edges. The image prior models both the smoothness of PET images and the similarity between functional boundaries in PET and anatomical boundaries in CT. Level set functions (LSFs) are used to represent smooth and closed functional boundaries. The proposed method does not assume an exact match between PET and CT boundaries. Instead, it encourages similarity between the two boundaries, while allowing different region definition in PET images to accommodate possible signal and position mismatch between functional and anatomical images. While the functional boundaries are guaranteed to be closed by the LSFs, the proposed method does not require closed anatomical boundaries and can utilize incomplete edges obtained from an automatic edge detection algorithm. We conducted computer simulations to evaluate the performance of the proposed method. Two digital phantoms were constructed based on the Digimouse data and a human CT image, respectively. Anatomical edges were extracted automatically from the CT images. Tumors were simulated in the PET phantoms with different mismatched anatomical boundaries. Compared with existing methods, the new method achieved better bias variance performance. The proposed method was also applied to real mouse data and achieved higher contrast than other methods. PMID- 21983560 TI - Anaplasma, Ehrlichia, and "Candidatus Neoehrlichia" bacteria: pathogenicity, biodiversity, and molecular genetic characteristics, a review. AB - The family Anaplasmataceae includes gram-negative obligate intracellular alphaproteobacteria, which amplify within membrane-bound vacuoles. The genera Anaplasma and Ehrlichia as well as the recently specified cluster "Candidatus Neoehrlichia" comprise all bacteria of the family that are transmitted by ixodid ticks to mammalian hosts and cause infections in humans and numerous domestic and wild animal species. Totally, six Anaplasma, five Ehrlichia, and two "Candidatus Neoehrlichia" species as well as a variety of Ehrlichia bacteria with undefined taxonomic position belong to tick-borne bacteria. This review briefs the ecology, pathogenic properties, and molecular genetic diversity of Anaplasmataceae validated species, "Candidatus" species, and undefined novel Ehrlichia genetic variants. PMID- 21983561 TI - Heligmosomoides polygyrus infection is associated with lower MHC class II gene expression in Apodemus flavicollis: indication for immune suppression? AB - Due to their key role in recognizing foreign antigens and triggering the subsequent immune response the genes of the major histocompatibility complex (MHC) provide a potential target for parasites to attack in order to evade detection and expulsion from the host. A diminished MHC gene expression results in less activated T cells and might serve as a gateway for pathogens and parasites. Some parasites are suspected to be immune suppressors and promote co infections of other parasites even in other parts of the body. In our study we found indications that the gut dwelling nematode Heligmosomoides polygyrus might exert a systemic immunosuppressive effect in yellow-necked mice (Apodemus flavicollis). The amount of hepatic MHC class II DRB gene RNA transcripts in infected mice was negatively associated with infection intensity with H. polygyrus. The hepatic expression of immunosuppressive cytokines, such as transforming growth factor beta and interleukin 10 was not associated with H. polygyrus infection. We did not find direct positive associations of H. polygyrus with other helminth species. But the prevalence and infection intensity of the nematodes Syphacia stroma and Trichuris muris were higher in multiple infected individuals. Furthermore, our data indicated antagonistic effects in the helminth community of A. flavicollis as cestode infection correlated negatively with H. polygyrus and helminth species richness. Our study shows that expression analyses of immune relevant genes can also be performed in wildlife, opening new aspects and possibilities for future ecological and evolutionary research. PMID- 21983562 TI - An actin-dependent mechanism for long-range vesicle transport. AB - Intracellular transport is vital for the function, survival and architecture of every eukaryotic cell. Long-range transport in animal cells is thought to depend exclusively on microtubule tracks. This study reveals an unexpected actin dependent but microtubule-independent mechanism for long-range transport of vesicles. Vesicles organize their own actin tracks by recruiting the actin nucleation factors Spire1, Spire2 and Formin-2, which assemble an extensive actin network from the vesicles' surfaces. The network connects the vesicles with one another and with the plasma membrane. Vesicles move directionally along these connections in a myosin-Vb-dependent manner to converge and to reach the cell surface. The overall outward-directed movement of the vesicle-actin network is driven by recruitment of vesicles to the plasma membrane in the periphery of the oocyte. Being organized in a dynamic vesicle-actin network allows vesicles to move in a local random manner and a global directed manner at the same time: they can reach any position in the cytoplasm, but also move directionally to the cell surface as a collective. Thus, collective movement within a network is a powerful and flexible mode of vesicle transport. PMID- 21983563 TI - Gene bookmarking accelerates the kinetics of post-mitotic transcriptional re activation. AB - Although transmission of the gene expression program from mother to daughter cells has been suggested to be mediated by gene bookmarking, the precise mechanism by which bookmarking mediates post-mitotic transcriptional re activation has been unclear. Here, we used a real-time gene expression system to quantitatively demonstrate that transcriptional activation of the same genetic locus occurs with a significantly more rapid kinetics in post-mitotic cells versus interphase cells. RNA polymerase II large subunit (Pol II) and bromodomain protein 4 (BRD4) were recruited to the locus in a different sequential order on interphase initiation versus post-mitotic re-activation resulting from the recognition by BRD4 of increased levels of histone H4 Lys 5 acetylation (H4K5ac) on the previously activated locus. BRD4 accelerated the dynamics of messenger RNA synthesis by de-compacting chromatin and hence facilitating transcriptional re activation. Using a real-time quantitative approach, we identified differences in the kinetics of transcriptional activation between interphase and post-mitotic cells that are mediated by a chromatin-based epigenetic mechanism. PMID- 21983564 TI - Misfolded proteins driven to destruction by Hul5. AB - Misfolded proteins are potentially toxic and are therefore subjected to highly selective degradation by the ubiquitin-proteasome system. The identification of the Hul5 ubiquitin ligase as a major mediator of such 'quality-control' ubiquitylation following heat shock raises new questions about the design of these pathways. PMID- 21983565 TI - Microtubules induce self-organization of polarized PAR domains in Caenorhabditis elegans zygotes. AB - A hallmark of polarized cells is the segregation of the PAR polarity regulators into asymmetric domains at the cell cortex. Antagonistic interactions involving two conserved kinases, atypical protein kinase C (aPKC) and PAR-1, have been implicated in polarity maintenance, but the mechanisms that initiate the formation of asymmetric PAR domains are not understood. Here, we describe one pathway used by the sperm-donated centrosome to polarize the PAR proteins in Caenorhabditis elegans zygotes. Before polarization, cortical aPKC excludes PAR-1 kinase and its binding partner PAR-2 by phosphorylation. During symmetry breaking, microtubules nucleated by the centrosome locally protect PAR-2 from phosphorylation by aPKC, allowing PAR-2 and PAR-1 to access the cortex nearest the centrosome. Cortical PAR-1 phosphorylates PAR-3, causing the PAR-3-aPKC complex to leave the cortex. Our findings illustrate how microtubules, independently of actin dynamics, stimulate the self-organization of PAR proteins by providing local protection against a global barrier imposed by aPKC. PMID- 21983566 TI - Hul5 HECT ubiquitin ligase plays a major role in the ubiquitylation and turnover of cytosolic misfolded proteins. AB - Cellular toxicity introduced by protein misfolding threatens cell fitness and viability. Failure to eliminate these polypeptides is associated with numerous aggregation diseases. Several protein quality control mechanisms degrade non native proteins by the ubiquitin-proteasome system. Here, we use quantitative mass spectrometry to demonstrate that heat-shock triggers a large increase in the level of ubiquitylation associated with misfolding of cytosolic proteins. We discover that the Hul5 HECT ubiquitin ligase participates in this heat-shock stress response. Hul5 is required to maintain cell fitness after heat-shock and to degrade short-lived misfolded proteins. In addition, localization of Hul5 in the cytoplasm is important for its quality control function. We identify potential Hul5 substrates in heat-shock and physiological conditions to reveal that Hul5 is required for ubiquitylation of low-solubility cytosolic proteins including the Pin3 prion-like protein. These findings indicate that Hul5 is involved in a cytosolic protein quality control pathway that targets misfolded proteins for degradation. PMID- 21983567 TI - Prosperity is associated with instability in dynamical networks. AB - Social, biological and economic networks grow and decline with occasional fragmentation and re-formation, often explained in terms of external perturbations. We show that these phenomena can be a direct consequence of simple imitation and internal conflicts between 'cooperators' and 'defectors'. We employ a game-theoretic model of dynamic network formation where successful individuals are more likely to be imitated by newcomers who adopt their strategies and copy their social network. We find that, despite using the same mechanism, cooperators promote well-connected highly prosperous networks and defectors cause the network to fragment and lose its prosperity; defectors are unable to maintain the highly connected networks they invade. Once the network is fragmented it can be reconstructed by a new invasion of cooperators, leading to the cycle of formation and fragmentation seen, for example, in bacterial communities and socio-economic networks. In this endless struggle between cooperators and defectors we observe that cooperation leads to prosperity, but prosperity is associated with instability. Cooperation is prosperous when the network has frequent formation and fragmentation. PMID- 21983568 TI - Lipid nanoparticles containing oryzalin for the treatment of leishmaniasis. AB - Oryzalin is a dinitroaniline drug that has attracted recent interest for the treatment of leishmaniasis. Its use as an antiparasitic therapeutic agent is limited by the low water solubility associated with an in vivo rapid clearance, leading to the administration of larger and possibly toxic doses in in vivo studies, and the use of solvents that may lead to undesirable side effects. In the present work oryzalin-containing lipid nanoparticles were produced by a emulsion-solvent evaporation technique using a composition suitable for parenteral administration, i.e., tripalmitin (solid lipid) and a complex mixture of three emulsifying agents (soya lecithin, Tween(r) 20 and sodium deoxycholate). Physicochemical characterization included the determination of mean particle size, polydispersity index, zeta potential, encapsulation efficiency and DSC studies. Final formulations revealed values of <140 nm (PI<0.2) and zeta potential of ~-35 mV, as well as encapsulation efficiency >75%. The effects of various processing parameters, such as lipid and surfactant and composition and concentration, as well as the stability during the harsh procedures of autoclaving (121 degrees C/15 min) and freeze-drying were also evaluated. Formulations revealed to be stable throughout freeze-drying and moist-heath sterilization without significant variations on physicochemical properties and no significant oryzalin losses. The use of a complex surfactant mixture proved crucial for preserving formulation stability. Particularly, lecithin appears as a key component in the stabilization of tripalmitin-based oryzalin-containing lipid nanoparticles. Finally, cell viability studies demonstrated that the incorporation of oryzalin in nanoparticles decreases cytotoxicity, thus suggesting this strategy may improve tolerability and therapeutic index of dinitroanilines. PMID- 21983569 TI - Substitution matters: isolating phosphorus diiminopyridine complexes. AB - The direct reactions of PI(3) with -H or -C(6)H(5) substituted diiminopyridine ligands yield the N,N',N''-chelated P(I) cations. The analogous chemistry with the ubiquitous -CH(3) substituted derivative produces a complex mixture of products underscoring the importance of the substitution on the alpha-carbon atom. The I(3)(-) counteranion of the compounds could be easily exchanged with the more robust B(12)Cl(12)(2-) dianion. Reactions of PCl(3) and PBr(3) with CH(3) and -C(6)H(5) substituted ligands led to indiscernible mixtures or no reaction. However, heating PBr(3) with the -H derivative in the presence of a halide trap produced the corresponding phosphorus(I) cation as the bromide salt. These species represent the first phosphorus diiminopyridine complexes reported. PMID- 21983570 TI - [Sternal osteosynthesis after cardiac surgery]. AB - Sternal fixation with nickelide titanium staples with shape memory effect is considered to be a novel method of wound closure after cardiac operations. The study includes data of 140 patients and is devoted to the preliminary assessment of the use of the mentioned fixators with self-regulating compression. Osteosynthesis proved to be completely effective in 136 (97,1%) patients. The use of nitinol staples allows not only a secure sternal fixation with minimal risk of underlying structures' trauma, but decreases time of postoperative patients' rehabilitation after the major cardiac surgery. PMID- 21983571 TI - [Surgical treatment of chronic abdominal ischemia]. AB - The study includes data of 139 patients with chronic abdominal ischemia, due to hemodynamically significant occlusion of impaired visceral aortic branches. The diagnosis was confirmed by aortography, computed tomoangiography and duplex color angioscanning. Immediate and long-term results of 49 reconstructive and conditionally reconstructive operations, 11 transcutaneous endovascular angioplasty, as well as postoperative complications, were analyzed. PMID- 21983572 TI - [Surgical treatment of patients with nonrheumatic aortic valve failure and ischemic heart disease]. AB - 54 patients aged 65-88 years (mean age 68,4+/-5,9) were operated during 1994 2009. 50 patients underwent aortic valve replacement combined with coronary bypass grafting, 3 patients underwent aortic and mitral valve replacement combined with bypass grafting. Ascending aorta replacement according to Bentall - de Bono method with coronary bypass grafting was carried out to 1 patient. Aortic root plasty was applied in 4 observations. 106 distal bypasses with coronary bed were formed in 54 patients; myocardial revascularization index amounted 1,9. Hospital mortality amounted 3,7% (2 patients). Causes of lethal outcome were: complex rhythm disturbances, augmenting cardiovascular failure. Low hospital mortality and low amount of complications allow recommending more aggressive approach in establishing indications for operative treatment in this group of patients. PMID- 21983573 TI - [Computed tomography in diagnostics and treatment of traumatic retroperitoneal hemorrhage]. AB - Causes of retroperitoneal bleeding (RB) were specified basing on retrospective analysis of 60 observations of closed abdominal injury. Two types of RB, with formation of blood packets and "impregnation", were marked out each having their computer tomography singes, changing during treatment. Contrast-enhanced computer tomography enabled to detect persisting bleeding from kidney or spleen, set indications for urgent laparotomy and reveal traumatic renal artery thrombosis even in the absence of hemoperitoneum. PMID- 21983574 TI - [Intraductal papillary-mucinous tumor of the pancreas: difficulties and mistakes of diagnostics and treatment]. AB - 15 patients with intraductal papillary-mucinous tumors (IPMT) of the pancreas were observed. Clinical manifestation corresponded with chronic pancreatitis. Ultrasound study, including endosonography, contrast-enhanced computer and magnetic resonance tomography were used in complex observation of the patients. Dilation of main or lateral pancreatic ducts, connection of tumor with pancreatic duct system and absence of septal calcinosis are typical signs in radiodiagnostics of IPMT. Visualization of parietal papillary proliferations and their contrast enhancement are undeniable signs f or neoplastic character of pancreatic duct dilation. Sensitivity of CT, MRT and endoUS amounted accordingly 66, 83 and 88%. All patients were operated. Extent of operation was determined by morphological character, localization and size of the tumor (pylorus-preserving pancreaticoduodenal resection was carried out to 6 patients, distal resection including robot-assisted - to 7 patients, midline resection - to 1 patient, duodenum-preserving resection of head and body of pancreas - to 1 patient). Intraoperative urgent histologic study of pancreatic section was carried out by all means. Tumors with borderline degree of malignancy were detected in 4 cases. PMID- 21983575 TI - [Rate of biliary ducts' decompression by the tumorous obstructive jaundice]. AB - Results of biliary decompression were analyzed in 185 patients with malignant obstructive jaundice. Among them 85 patients underwent nasobiliary drainage, 37 - percutaneous transhepatic bile drainage and 63 - cholecystectomy. Dynamics in biochemical indices of blood serum, cholangiomanometry and jaundice response to decompression according to T. Shimizu et K.Yoshida's formula in our modification were evaluated for estimation of bile flow rate. It is ascertained that application of nasobiliary drainage leads to low-rate decompression, percutaneous transhepatic bile drainage and cholecystectomy - to high-rate decompression. Low rate decompression enables to decrease significantly the frequency of "fast decompression syndrome" and complications, particularly augmenting of liver dysfunction, multiple organ failure and lethality in post-decompression period related to them. PMID- 21983576 TI - [Hepatopancreatoduodenal resection - are there any perspectives?]. AB - 1380 operations on liver, mostly for metastatic lesions were carried out during 1990-2010 years. Gastro-pancreaticoduodenal resection for lesions with periampullary localization was carried out to 580 patients. Combined surgical intervention on liver and pancreas was carried out in 20 cases. These observations formed our study. Direct and long-term results of treatment were analyzed in operated patients. It is shown gastropancreaticoduodenal resection though having high level of postoperative complications is well tolerated and can be recommended for wide application in clinical practice. PMID- 21983577 TI - [Prediction of acute biliary pancreatitis]. AB - Authors propose mathematical model for prediction of acute biliary pancreatitis in patients with strangulated concrements of papilla Vateri. Values of alpha amylase and lipase in blood and bile are used as main prognostic signs. It is estimated that blood lipase, bile alpha-amylase and lipase are main prognostic signs for development of acute biliary pancreatitis. PMID- 21983578 TI - [The repeated operations for focal liver lesions]. AB - Repeated operations for focal liver lesions were analyzed. 75 patients with parasitic liver lesions (alveococcosis, echinococcosis), 14 patients with liver tumors, 15 patients with cysts and abscesses were included in the study. For the first time patients underwent palliative operations or diagnostic laparotomy. In some patients relapse was observed after radical surgery in postoperative period. Ultrasound study was the main diagnostic method for detecting localization and extent of the lesion. 91 patients underwent radical surgery, including hemihepatectomy carried out to 26 patients, segmental and bisegmental liver resections carried out to 35 patients. Transparenchymatous Tung ligation was used in liver resections. Resection line was covered by hemostatic sutures according to B.I. Alperovich technique. Intraparenchymatous processing of Glisson pedicle according to E.I. Galperin method was applied in extensive liver resections. Cryodestruction was used for prophylaxis of relapses in parasitic and tumor lesions. Liver failure (4) and bleedings (2) were the most life-threatening postoperative complications. 4 patients died due to liver failure (2) and bleedings (2). Among 97 patients good results were observed in 73 (75,3%) patients, satisfactory - in 22 (22,7%), poor - in 2 (2,1%) with relapse of hepatocellular carcinoma. PMID- 21983579 TI - [Severity assessment and prognosis definition in patients with the acute pancreatitis]. AB - Investigation of white blood cell and lymphocyte concentration and white blood cell intoxication index (WBCII), integral systems APACHE II and Ranson reliably reflected the severity of clinical status in patients with acute pancreatitis and had prognostic value. At the same time white blood cell concentration and indices of APACHE II reflected to lesser extent the severity of clinical status, and white blood cell concentration didn't have any prognostic value. Application of lymphocyte concentration and WBCII can be recommended in urgent surgery for evaluation of clinical status and prognosis at early stages of diagnostics and treatment of acute pancreatitis. PMID- 21983580 TI - [Surgical treatment of colorectal cancer liver metastases with microwave thermoablation]. AB - Domestic device for destruction of tumors by microwave power was designed. Initial series of laboratory experiments were performed with microwave liver ablation. Primary series of patients with colorectal cancer metastases to the liver demonstrate positive results. Short-term exposure, programmable shapes and sizes of ablative zones are the distinctive advantages of microwave thermoablation (MTA). 329 patients underwent liver resections during 2005-2010 years.108 patients had colorectal cancer metastases to the liver. 52 (48,14%) patients had bilobar liver lesions. Among them 11 patients underwent liver resection combined with MTA of contralateral liver lesions. Reliable differences in survival rates among patients with monolobar and bilobar metastatic lesions were not observed. Median of survival rate amounted 22.8 months in patients operated for metastatic colorectal cancer. Variants of surgical treatment are proposed. PMID- 21983581 TI - [Ways to improve medical help by deep massive burns in rural area]. AB - Results of treatment were analyzed in 907 patients with extensive deep burns. It is shown that early large necrectomy and saving methods of skin plasty (microautodermoplasty) enables to improve significantly the results of surgical treatment in patients with deep burns. It is proved that introduced regional specialized hospitals with high-tech combustiology profile allow improving health care in such patients. PMID- 21983582 TI - [Robotic assisted surgery in gynecology]. AB - 80 operations for various gynecological diseases were carried out using system. The technique of operations and short-term results are described. PMID- 21983583 TI - [The assessment of long-term results of surgical treatment of patients with secondary lymphostasis lower extremity in predicting the course of the disease]. AB - With the development of vascular surgery began to attract attention to the problem of studying the long-term results of treatment. Long-term results of surgical treatment were studied in 110 patients with secondary lymphostasis lower extremities in the period 1997-2010. The estimation was made in two ways. First, the definition of value of basic clinical and social indicators, and secondly, the study target quality of life of patients. The analysis of remote results of treatment of patients with secondary lymphostasis lower extremities indicates that the quality of life and values of major clinical and social indicators quite adequately characterize the patient's condition after treatment and can be used alongside traditional medical data to assess long-term results, as well as serve as criteria in solving the optimal choice of treatment. PMID- 21983584 TI - [Robotic assisted distal pancreatic resection for insulinoma]. PMID- 21983585 TI - [Possibilities of the surgical treatment of patients with perforative duodenal ulcer, admittad in hospital in terminal state]. PMID- 21983586 TI - [The combined surgery by the full-time abdominal pregnancy]. PMID- 21983587 TI - The effectiveness of community based physical activity interventions with Aboriginal peoples. AB - Though historically rare, Aboriginal individuals continue to experience greater levels of cardiovascular disease than the general Canadian population. Increasing evidence indicates rising sedentary behaviors from the traditional healthy and active lifestyles of this population. OBJECTIVE: This investigation aimed to examine the health benefits of a community-based physical activity intervention for Aboriginal Canadians. METHODS: From 2007-2010, 273 participants from the province of British Columbia, Canada were recruited through 21 Aboriginal communities representing male and females of wide ranging ages and health statuses. Participants attended identical testing of body composition, blood pressure, total and high density lipoprotein cholesterols, and physical activity behavior pre-and post-training. Participants completed one of three self-selected 13 week interventions: walking (n=149), walk/running (n=86), or running (n=27). RESULTS: Improvements in health measures were observed for both male and female participants of all age groups and all three training programs. Male and female participants' improvements included waist circumference: 2.7 cm and 2.2 cm, total cholesterol: 0.18 mmol/L and 0.12 mmol/L, and systolic blood pressure: 2.6mm Hg and 1.5mm Hg, respectively. CONCLUSIONS: The self-selected intensities program was successful in improving health status and physical activity for Aboriginal adults of all ages, genders and activity programs. PMID- 21983588 TI - T-cell-depleting agents in kidney transplantation: is there a place for alemtuzumab? PMID- 21983590 TI - Association of the FokI polymorphism in the vitamin D receptor gene with vertebral fracture in Iranian postmenopausal women. PMID- 21983595 TI - Revisiting the Wilson-Jungner criteria: How can supplemental criteria guide public health in the era of genetic screening? AB - PURPOSE:: Advances in technology have made newborn screening for more than 50 inborn errors of metabolism possible using a dried blood sample. A framework is proposed that public health practitioners may use when considering candidate disorders for newborn screening panels. METHODS:: The framework expands on the 10 Wilson-Jungner criteria with the addition of 11 criteria specific to newborn screening. A calculation, the "pNBS Decision Score," is used to quantify results and rank candidate disorders. RESULTS:: The pNBS Decision Scores that were calculated for phenylketonuria (OMIM# 261600), cystic fibrosis (OMIM# 219700), Pompe disease (OMIM# 232300), and severe combined immunodeficiency (OMIM# 102700) support their inclusion as newborn screening disorders. The pNBS Decision Score suggests that Krabbe disease (OMIM# 245200) is not a candidate disorder for inclusion at this time. CONCLUSION:: The proposed framework adds to the ability of policy makers to quantify an essential portion of the process for adding disorders to newborn screening panels. Other factors such as ethical, legal, and social issues, clinical utility, and advocacy are also part of the policy process. The framework is not intended to replace existing nomination processes but rather to enhance those processes by encouraging iterative review of newborn screening-specific criteria. The use of the framework will provide consistency across a portion of the decision process. The public health community should take the opportunity to revisit the screening determinants of the Wilson-Jungner criteria from a 21st century perspective. The results suggest that this framework provides the public health practitioner with a consistent process for making an evidence-based decision. PMID- 21983596 TI - Brucella abortus efp gene is required for an efficient internalization in HeLa cells. AB - Numerous chromosomal virulence genes (chv) have been shown to play an important role in the ability of Agrobacterium tumefaciens to transform plants. The A. tumefaciens chvH gene encodes a protein similar in sequence to the Escherichia coli elongation factor P (EF-P). In A. tumefaciens this factor is required for tumor formation and for full expression of the vir genes, exerting its activity at a post-transcriptional level. Cross-complementation assays suggest that the chvH gene and the efp gene of E. coli are functionally homologous. We have cloned and characterized the efp homolog gene in Brucella abortus which has 45% identity to A. tumefaciens chvH and 35% identity to E. coli efp. The gene complemented detergent sensitivity and virulence in the chvH A. tumefaciens mutant, suggesting that both genes are functionally homologous; the growth rate in complex medium also increased to wild type levels. An efp mutant in B. abortus 2308 grew slower in complex media and showed more sensitivity to detergents. Infection assays in J774 macrophage like cells revealed no significant differences between the wild type and the efp mutant strains. The recovery of this mutant from spleens of inoculated mice was equivalent compared to that of the parental strain suggesting that B. abortus efp is not required for virulence in an animal model. However the efp mutant revealed significant differences at 1 h-4 h post-infection in HeLa infection assays compared to the wild type strain, indicating that cellular internalization was affected in non-professional phagocytes. Double immunofluorescence assays for detecting extracellular and intracellular bacteria, demonstrated that the mutant attaches to HeLa cells as the wild type but is deficient in the internalization process, thus indicating that efp is involved in the penetration of Brucella in non-professional phagocytes. PMID- 21983597 TI - Inhibition of HIV entry by extracellular glucuronoxylomannan of Cryptococcus neoformans. AB - Cryptococcosis, caused by Cryptococcus neoformans, is the most common opportunistic fungal disease in HIV/AIDS patients. The prognosis of AIDS patients with Cryptococcus infection is very poor. One of the major characteristics in cryptococcosis patients is the presence of high concentrations of the cryptococcal capsule polysaccharide (CCP) in the serum and cerebrospinal fluid. CCP enhances HIV replication in H9 T-cells, but the mechanism is unknown. In this study, we tested whether extracellular glucuronoxylomannan (GXM), a major component of CCP, enhances HIV entry using replication-incompetent HIV and a cell line which expresses a stable amount of CD4 and both of the HIV co-receptors. Extracellular GXM had no effect on cell-cell fusion however; viral entry surprisingly was inhibited by GXM. Hence, any enhancement of replication must be due to an effect that occurs post-entry. PMID- 21983598 TI - Isolation of laccase gene from Bacillus subtilis and analysis of its physicochemical properties. AB - The present study reports the cloning and sequencing of lac2 from Bacillus subtilis. The gene is composed of 1542 bp and encodes a 514-amino acid protein. The gene has 86% homology with a published laccase with GeneID 936023. The lac2 gene was deposited in GenBank as a new nucleotide sequence. This new sequence was cloned into the multiple cloning site of pPIC9K to generate pPIC9K-lac2, which was then transformed into Pichia pastoris GS115 via electroporation. The recombinant GS115 (pPIC9K-lac2) was grown initially in BMGY medium and transferred to BMMY to induce gene expression for 48 h. The recombinant Lac2 protein shows laccase activity with alpha-naphthol and guaiacol as substrates. The optimal pH is between 3.2 and 4.7, and the optimal temperature is 25 degrees C for enzyme reaction. PMID- 21983599 TI - Approaches to efficient molecular catalyst systems for photochemical H2 production using [FeFe]-hydrogenase active site mimics. AB - The research on structural and functional biomimics of the active site of [FeFe] hydrogenases is in an attempt to elucidate the mechanisms of H(2)-evolution and uptake at the [FeFe]-hydrogenase active site, and to learn from Nature how to create highly efficient H(2)-production catalyst systems. Undoubtedly, it is a challenging, arduous, and long-term work. In this perspective, the progresses in approaches to photochemical H(2) production using mimics of the [FeFe] hydrogenase active site as catalysts in the last three years are reviewed, with emphasis on adjustment of the redox potentials and hydrophilicity of the [FeFe] hydrogenase active site mimics to make them efficient catalysts for H(2) production. With gradually increasing understanding of the chemistry of the [FeFe]-hydrogenases and their mimics, more bio-inspired proton reduction catalysts with significantly improved efficiency of H(2) production will be realized in the future. PMID- 21983600 TI - The proteoglycan bikunin has a defined sequence. AB - Proteoglycans are complex glycoconjugates that regulate critical biological pathways in all higher organisms. Bikunin, the simplest proteoglycan, with a single glycosaminoglycan chain, is a serine protease inhibitor used to treat acute pancreatitis. Unlike nucleic acids and proteins, whose synthesis is template driven, Golgi-synthesized glycosaminoglycans are not believed to have predictable or deterministic sequences. Bikunin peptidoglycosaminoglycans were prepared and fractionated to obtain a collection of size-similar and charge similar chains. Fourier transform mass spectral analysis identified a small number of parent molecular ions corresponding to monocompositional peptidoglycosaminoglycans. Fragmentation using collision-induced dissociation unexpectedly afforded a single sequence for each monocompositional parent ion, unequivocally demonstrating the presence of a defined sequence. The biosynthetic pathway common to all proteoglycans suggests that even more structurally complex proteoglycans, such as heparan sulfate, may have defined sequences, requiring a readjustment in the understanding of information storage in complex glycans. PMID- 21983601 TI - A mass spectrometry-guided genome mining approach for natural product peptidogenomics. AB - Peptide natural products show broad biological properties and are commonly produced by orthogonal ribosomal and nonribosomal pathways in prokaryotes and eukaryotes. To harvest this large and diverse resource of bioactive molecules, we introduce here natural product peptidogenomics (NPP), a new MS-guided genome mining method that connects the chemotypes of peptide natural products to their biosynthetic gene clusters by iteratively matching de novo tandem MS (MS(n)) structures to genomics-based structures following biosynthetic logic. In this study, we show that NPP enabled the rapid characterization of over ten chemically diverse ribosomal and nonribosomal peptide natural products of previously unidentified composition from Streptomycete bacteria as a proof of concept to begin automating the genome-mining process. We show the identification of lantipeptides, lasso peptides, linardins, formylated peptides and lipopeptides, many of which are from well-characterized model Streptomycetes, highlighting the power of NPP in the discovery of new peptide natural products from even intensely studied organisms. PMID- 21983603 TI - Causes, risks, and probabilities: probabilistic concepts of causation in chronic disease epidemiology. AB - Identifying and understanding causes of disease is arguably the central aim of the discipline of epidemiology. However, while the discipline has matured over the past sixty years, developing a battery of quantitative tools and methods for data analysis, the discipline of epidemiology lacks an explicit, shared theoretical account of causation. Moreover, some epidemiologists exhibit discomfort with the concept of causation itself, concerned that it creates more confusion than clarity. This paper describes how, during the post-war period, epidemiologists began to think about causation in new ways as they encountered novel challenges in studying chronic diseases. The epidemiologic evidence linking cigarette smoking and lung cancer in the 1950s provided a focus for debates over causation. While some epidemiologists embraced probabilistic concepts of cause and effect, others maintained that causal mechanisms must ultimately be deterministic. The tension between probabilistic risk factors and deterministic causal mechanisms continues to haunt epidemiology today. PMID- 21983602 TI - Discovery of parallel pathways of kanamycin biosynthesis allows antibiotic manipulation. AB - Kanamycin is one of the most widely used antibiotics, yet its biosynthetic pathway remains unclear. Current proposals suggest that the kanamycin biosynthetic products are linearly related via single enzymatic transformations. To explore this system, we have reconstructed the entire biosynthetic pathway through the heterologous expression of combinations of putative biosynthetic genes from Streptomyces kanamyceticus in the non-aminoglycoside-producing Streptomyces venezuelae. Unexpectedly, we discovered that the biosynthetic pathway contains an early branch point, governed by the substrate promiscuity of a glycosyltransferase, that leads to the formation of two parallel pathways in which early intermediates are further modified. Glycosyltransferase exchange can alter flux through these two parallel pathways, and the addition of other biosynthetic enzymes can be used to synthesize known and new highly active antibiotics. These results complete our understanding of kanamycin biosynthesis and demonstrate the potential of pathway engineering for direct in vivo production of clinically useful antibiotics and more robust aminoglycosides. PMID- 21983604 TI - Nanocapsules prepared via nanoprecipitation and emulsification-diffusion methods: comparative study. AB - The encapsulation of hydrophobic drugs has been widely investigated using mainly oil phase in order to enhance the encapsulation efficiency. However, the effect of the starting materials on the colloidal properties of the final nanocapsules irrespective of the elaboration process has been neglected, and the hydrophobic drug location in the disperse media has not been completely elucidated. Therefore, this paper describes the effect of the oil used in the recipe and the preparation method on the behavior of nanocapsules prepared via nanoprecipitation and via emulsification-diffusion. The colloidal stability of the final dispersions, drug location and the drug release are preparation method dependent. In turn, the type of oil governs drug encapsulation efficiency regardless of the method and the size when nanocapsules are prepared by nanoprecipitation. PMID- 21983605 TI - Comparative pharmacoscintigraphic and pharmacokinetic evaluation of two new formulations of inhaled insulin in type 1 diabetic patients. AB - In this open, single-dose study, we compared the lung deposition and bioavailability of two newly developed insulin formulations for pulmonary delivery. Twelve type 1 diabetic patients were administered the two insulin products (2 U/kg b.w.), which had been radiolabelled with (99m)Tc. The formulations were either microparticles of insulin without excipients (F1) or lipid-coated insulin microparticles (F2). Lung deposition was assessed by gamma scintigraphy imaging performed immediately after administration. Bioavailability was evaluated by quantifying serum insulin levels over a period of 6 h. Lung deposition was found to be 50 +/- 9% and 24 +/- 8% for the F1 and F2 formulations, respectively. The insulin AUC0-360 ratio of F1/F2 was 188%, which was consistent with scintigraphic imaging. The concordance between imaging and biological results suggests that the lower bioavailability of F2 is due to its lower lung deposition and not to a reduced absorption into the blood stream. Additional in vitro experiments indicated that the lower performance of F2 was most probably related to a lower disaggregation efficiency of the powder when administered at a sub-optimal flow rate. The two formulations showed interesting pharmacokinetic profiles (T(max) of 26 and 16 min for F1 and F2, respectively) that mimic the physiological insulin secretion pattern. The bioavailability of the developed formulations was within the range of other DPI insulin formulations that have reached the final stages of clinical development. PMID- 21983606 TI - Design space approach in the optimization of the spray-drying process. AB - From a quality by design perspective, the aim of the present study was to demonstrate the applicability of a Bayesian statistical methodology to identify the Design Space (DS) of a spray-drying process. Following the ICH Q8 guideline, the DS is defined as the "multidimensional combination and interaction of input variables (e.g., materials attributes) and process parameters that have been demonstrated to provide assurance of quality." Thus, a predictive risk-based approach was set up in order to account for the uncertainties and correlations found in the process and in the derived critical quality attributes such as the yield, the moisture content, the inhalable fraction of powder, the compressibility index, and the Hausner ratio. This allowed quantifying the guarantees and the risks to observe whether the process shall run according to specifications. These specifications describe satisfactory quality outputs and were defined a priori given safety, efficiency, and economical reasons. Within the identified DS, validation of the optimal condition was effectuated. The optimized process was shown to perform as expected, providing a product for which the quality is built in by the design and controlled setup of the equipment, regarding identified critical process parameters: the inlet temperature, the feed rate, and the spray flow rate. PMID- 21983607 TI - [Results of fibrin clot application for acceleration of regeneration of the damaged mandible in experiment]. AB - The processes of regeneration of the damaged rat bottom jaw bone after application of enriched thrombocytes a fibrin clot were studied by morphological and radiovisiographic methods. At a natural course of regeneration the artificial aperture of bone was filled with blood and there the blood clot was formed. After 1 week the separate bone islets of a young tissue occurred in bone defect. In 2-3 weeks the aperture in a bottom jaw bone was completely closed by a young bone tissue. After operation with filling of bone bottom jaw defect by fibrin clot there was no formation of a blood clot. Already after 1 week the bone tissue defect was filled by the merged islets of again generated bone. By second week after fibrin use the further formation of bone tissue in defect and formation of a bone callosity was noted. PMID- 21983608 TI - [Effect of antibacterial and immunomodulating therapy on cytokine status in the infectious-inflammatory complications of dental surgical interventions]. AB - In patients with infectious-inflammatory complications after surgery in the oral cavity (cystectomy, dental implants, sinus lifting and removal of third molars) in the dynamics studied the content of pro-inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha). A significant change in their content in blood serum, and their contents increased in the early postoperative period with normalization of cytokine levels within 2 weeks after antibiotical and immunomodulatory treatment. PMID- 21983609 TI - [Mechanisms of bacteria translocation in generalized chronic parodontitis]. AB - Peculiarities of behavior reactions of bacteria-symbionts created conditions for the selection of translocators-strains. In microsymbiocenosis of parodontal pockets, from which translocation of bacteria into the blood was observed, the number of signals from intermicrobial communication, inhibiting the expression of the factors of colonization, virulence and persistence, was decreasing. Meanwhile, the number of signals on the increase of the expression of the factors given was increased. In 75% of cases strains-translocators were leaders; they gave more often signals on the inhibition of the growth of other strains symbionts. PMID- 21983610 TI - [Methods of roentgenologic study comprehension for appreciation of root canal obturation quality]. AB - Comparison of methods comprehension was done with intraoral roentgenography, orthopantomography (OPG), cone-beam computer tomography (CBCT) on the devices with optical amplifier of roentgenologic image (OARI) and sensor resolution (SR) 2 pair of lines per mm and without OARI with SR 2.5 pair of lines per mm. There were used extracted earlier teeth with adequate root canal obturation. According to the results of the study the image received with the help of CBCT with high SR let have the biggest information volume about filling quality of root canal and root canal structure peculiarities that testified to pro of the method over CBCT with OARI. The most widespread in the practice methods of intraoral roentgenography and orthopantomography not in all cases reflected reliably the root canal obturation degree. PMID- 21983611 TI - [Comparative evaluation of marginal adaptation of restorative materials after cavity preparation with different tools in vitro]. AB - In this article the results of laboratory studies that evaluated the marginal adaptation of restorative materials after the preparation of the cavity with different tools in vitro were presented. PMID- 21983612 TI - [Results of efficacy investigation of the toothpastes with natural compounds]. AB - The examination of hard tissues, periodontal and hygiene indices was conducted in 56 patients to determine the efficacy of toothpastes with natural compounds. According to the results, the natural compounds did not alter the color of the hard tissues, but also improved the hygienic status and lessened the periodontal inflammation manifestation in the oral cavity. PMID- 21983613 TI - [Experience in the use of frontal flap for reconstructive surgery of eyelids]. AB - Results of the use of classic Indian and petalous frontal flaps for surgical treatment of 52 patients of the age from 11 till 58 years with congenital and acquired eyelid defects were presented. In all cases eyelid form and function it was possible to restore, reduce the number of operations and achieve maximal esthetic rehabilitation in the terms to 1 year from the patient addressing to clinic and in patients with congenital oblique face clefts - before achieving the age of 14-16 years. Frontal flap use on medial, paramedical and lateral pedicles considerably widened reconstructive blepharoplastics possibilities and increased efficacy of treatment of the patients with congenital and acquired limited total and subtotal eyelid defects. PMID- 21983614 TI - [Application of ultrasonography in diagnosis and treatment of acute inflammation of soft tissues in maxillofacial region and neck]. AB - We investigated the value of ultrasonography (USG) and ultrasound-guided aspirations in diagnosis and treatment of acute inflammation of soft tissues in maxillofacial region and neck. We performed 174 USG in 136 patients (73 with abscesses and phlegmons, 27 with acute lymphadenitis, 16 with inflamed cysts, 12 with parotitis, 3 with sialolithiasis and 5 with diseases, simulated acute inflammation). Ultrasound-guided aspirations performed in 35 patients. We considered USG to be useful diagnostic tool in acute inflammation of soft tissues in maxillofacial region and neck. USG allowed to determine localization and stage of inflammation, discriminate it from non-inflammatory diseases and improve assessment of its dynamics. Ultrasound-guided aspirations was a valuable tool for diagnostic and treatment purposes in inflamed cysts. PMID- 21983615 TI - [Application of endovascular methods in complex diagnostics and treatment of tongue angiodysplasias]. AB - In article experience of diagnostics and treatment of 30 patients with angiodysplasia of the tongue was given. The surgical treatment was made to 21 patients with vascular malformation of the tongue, selective bilateral catheterization of lingual arteries and endovascular microembolization by PVA - 250-400 MU was successfully performed in 4 cases, transcutaneus sclerotherapy with solution aethoxyskleroli 0,5% in 3 cases was successfully provided. Advantages of endovascular diagnostics and treatment methods angiodysplasias of the tongue were shown. PMID- 21983616 TI - [Reactive-dystrophic processes in salivary glands (sialoadenoses) running on the background of metabolic syndrome]. AB - Basing upon comprehensive checkup of 82 patients with metabolic syndrome authors made diagnostics of different forms of sialoadenosis in them. The disease proceeded on the background of abdominal adiposity, lipid metabolism derangements, glucose toleration disturbances and diabetes mellitus of the 2nd type with reduction of tissue sensitivity to insulin (insulin resistivity). Results of the fulfilled patient treatment showed that it was necessary to include in the complex of therapeutic measures metformine (glukofagee) producing positive effect upon carbohydrate metabolism and also to normalize the work of glands increasing their secretory activity. PMID- 21983617 TI - [Diagnostics and treatment of patients with mandible salient angles]. AB - Problem of diagnostics and treatment of patients with disproportion of lower face zone was discussed which was expressed in the form of mandible salient angles and produced aesthetic problem to many people especially to womanhood. Complex of diagnostic methods was offered that gave the possibility to differentiate types of pathology into groups for easing method of treatment chose. Methods of treatment were listed allowing to receive high aesthetic and functional results. PMID- 21983618 TI - [Experience in working out of tools of quality management of maxillofacial prosthetics]. AB - Expericnce of working out of tools of quality management of maxillofacial prosthetics which can be applied in clinical practice of maxillofacial orthopedy is presented. The fragment of the algorithm of maxillofacial prosthetics developed by authors is presented. PMID- 21983619 TI - [Study of physical-mechanic characteristics of prosthetic construction after their adjustment with the use of laser welding and hot metal adding]. AB - Study of physical-mechanic characteristics of connecting joints of beam construction after laser welding and hot metal adding was performed. Increase of microhardness of joints as well as small reduction of bending strength of prosthetic constructions was established. PMID- 21983620 TI - [Long-term results following mandibular resection in newborns with autogeneous rib graft for reconstruction of mandibular defects]. AB - The authors report on the clinical course of two children, in whom benign tumors with destruction of the mandible were diagnosed at the age of 4 and 6 months respectively. Following mandibular continuity resection the lateral mandible was reconstructed with autogenous rib grafts. In both children craniofacial and mandibular growth was assessed during yearly clinical and radiological follow-up visits. A slight vertical overgrowth and transversal growth inhibition could be detected. PMID- 21983621 TI - [Classification of the formations from blood vessels of maxillofacial region and neck in children]. AB - Multidisciplinary group of investigators basing upon special literature study, analysis of their own observation (1168 cases) including retrospective for 20 years and with the help of several following methods - clinical, roentgenological, pathomorphological,immunohistochemical - picked out from wide group of the so called hemangiomas 3 types of lesions: hyperplasia, malformation, tumour and suggested their clinical biological classification. To each of lesion types characteristic was given. PMID- 21983622 TI - Nonparametric estimation of age-specific reference percentile curves with radial smoothing. AB - Reference percentile curves represent the covariate-dependent distribution of a quantitative measurement and are often used to summarize and monitor dynamic processes such as human growth. We propose a new nonparametric method based on a radial smoothing (RS) technique to estimate age-specific reference percentile curves assuming the underlying distribution is relatively close to normal. We compared the RS method with both the LMS and the generalized additive models for location, scale and shape (GAMLSS) methods using simulated data and found that our method has smaller estimation error than the two existing methods. We also applied the new method to analyze height growth data from children being followed in a clinical observational study of growth hormone treatment, and compared the growth curves between those with growth disorders and the general population. PMID- 21983623 TI - Nurse Practitioners' attitudes about cancer clinical trials and willingness to recommend research participation. AB - BACKGROUND: Recruitment and retention of human participants in cancer clinical trials remains challenging for all investigators. Nurse Practitioners (NPs) are in a prime position to discuss, educate and refer patients to clinical trials as many NPs work in ethnically and geographically diverse primary care settings in the U.S., yet they remain an untapped resource. We examined NPs' general attitudes toward cancer clinical trial recommendations and assessed their willingness to recommend such trials METHODS: We randomly surveyed 455 primary care NPs in the state of Pennsylvania during 2008 with an adjusted response rate of 55.3%. Descriptive statistics were used to characterize NPs' demographic and practice characteristics, and logistic regression was used to assess the relative influence of the various attitudes and beliefs on the likelihood that the NP would bring up clinical trials as a treatment option. RESULTS: NPs were more likely to bring up the topic of clinical trials with at least some patients if they were comfortable discussing treatment options with their cancer patients (OR=4.29, p=0.001), were comfortable discussing options of entering a clinical trial for treatment (OR=3.54, p=0.003), had adequate time during patients' visit to explain clinical trials (OR=3.40, p=0.008), and if they believed that patients in clinical trials were receiving the best medical treatment (OR=3.34, p=0.019). NPs who were comfortable discussing cancer clinical trials were almost 5 times more likely to think clinical trials were useful (OR=4.70; 95% CI=1.81-12.19; p=0.001). Nearly three-quarters (72.6%) of the entire responder sample reported three or more ethical concerns associated with clinical trials, including issues of randomization, informed consent, and patient burden. CONCLUSIONS: NPs are willing to recommend clinical trials but need more education about the benefits and burdens of clinical trials, the associated ethical concerns, and evidence regarding the translatability of research to clinical practice to increase their knowledge and comfort level with discussing clinical trials. PMID- 21983624 TI - Hybridization of conditional and predictive power for futility assessment in sequential clinical trials with time-to-event outcomes: a resampling approach. AB - Having the potential to stop a clinical trial early for futility during an interim analysis is an important feature of sequential clinical trials. Conditional power and predictive power methods are widely used to analyze interim data in determining whether a trial is likely to eventually demonstrate both statistically significant and clinically meaningful results. Herein we introduce a new approach to early stopping in clinical trial designs, which can be viewed as a hybridization of the conditional and predictive power methods and has both methods as its special cases. The proposed hybridization, along with a novel resampling method, can be used together to assess futility in sequential trials with time-to-event outcomes. The proposed approach to futility assessment applies to sequential clinical trials with interim analyses planned at either fixed calendar times or number of events. In addition, it does not resort to asymptotics and applies to general test statistics of either single or multiple dimensions. PMID- 21983625 TI - Better exercise adherence after treatment for cancer (BEAT Cancer) study: rationale, design, and methods. AB - Most breast cancer survivors do not engage in regular physical activity. Our physical activity behavior change intervention for breast cancer survivors significantly improved physical activity and health outcomes post-intervention during a pilot, feasibility study. Testing in additional sites with a larger sample and longer follow-up is warranted to confirm program effectiveness short and longer term. Importantly, the pilot intervention resulted in changes in physical activity and social cognitive theory constructs, enhancing our potential for testing mechanisms mediating physical activity behavior change. Here, we report the rationale, design, and methods for a two-site, randomized controlled trial comparing the effects of the BEAT Cancer physical activity behavior change intervention to usual care on short and longer term physical activity adherence among breast cancer survivors. Secondary aims include examining social cognitive theory mechanisms of physical activity behavior change and health benefits of the intervention. Study recruitment goal is 256 breast cancer survivors with a history of ductal carcinoma in situ or Stage I, II, or IIIA disease who have completed primary cancer treatment. Outcome measures are obtained at baseline, 3 months (i.e., immediately post-intervention), 6 months, and 12 months and include physical activity, psychosocial factors, fatigue, sleep quality, lower extremity joint dysfunction, cardiorespiratory fitness, muscle strength, and waist-to-hip ratio. Confirming behavior change effectiveness, health effects, and underlying mechanisms of physical activity behavior change interventions will facilitate translation to community settings for improving the health and well-being of breast cancer survivors. PMID- 21983626 TI - Recruitment of a hidden population: African Americans with obsessive-compulsive disorder. AB - Obsessive-compulsive disorder (OCD) is a leading cause of disability worldwide, however for reasons that are poorly understood ethnic minority groups are not well represented in clinical research studies. Thus, although African Americans experience equivalent rates of OCD according to epidemiological surveys, the generalizability of findings from clinical trials remains unknown. Research designed to improve identification, assessment and treatment of OCD is an important public health priority. The purpose of this study is to report outreach methods used to recruit African American adults for participation in an OCD research study. A variety of methods were employed, including radio advertisements, public transportation advertising, community outreach, and online advertising. A total of 83 African American adult participants were recruited over a 9.5 month period at the University of Pennsylvania in Philadelphia, and given comprehensive psychiatric assessments. African Americans with OCD symptoms were reliably identified and assessed, for a total of 75 with lifetime OCD (4 past and 71 current diagnoses). There was variability in the success and cost effectiveness of study recruitment methods. Radio ads were the most expensive means of recruitment, newspaper ads accounted for the largest number of eligible participants, and no cost methods such as Craig's List and word of mouth were also effective. The authors conclude that, with focused efforts, there are many effective methods for recruiting African Americans with OCD. Guidelines for recruitment are discussed, with a focus on cultural considerations. PMID- 21983627 TI - Fiberoptic bronchoscopy under noninvasive ventilation and propofol target controlled infusion in hypoxemic patients. AB - PURPOSE: In critically ill patients with acute respiratory failure (ARF), fiberoptic bronchoscopy and bronchoalveolar lavage (FOB-BAL) are important tools in diagnostic strategies. In nonintubated patients, the patient's agitation may lead to desaturation and compromise the realization of FOB. The aim of this study was to assess the feasibility and safety of target-controlled (TCI) propofol sedation during FOB-BAL in nonintubated hypoxemic patients. METHODS: The first end point in our prospective investigation within an intensive care unit (ICU) was the avoidance of endotracheal intubation within 24 h. Secondary end points were changes in the PaO(2)/FiO(2) ratio, hemodynamic stability, patient comfort, occurrence of adverse effects, and quality of FOB. Patients self-evaluated their comfort after FOB. RESULTS: Twenty-four FOBs were performed in 23 patients with ARF. PaO(2)/FiO(2) before FOB was 181 +/- 50 (range 85-286). All patients tolerated FOB with BAL. None was intubated during the 2 h after FOB. Loss of consciousness was obtained with an effect site concentration of propofol of 1.49 +/- 0.46 MUg/mL (range 2.6-0.6). No significant adverse events occurred. TCI propofol allowed us to obtain amnesia, patient comfort, and it did not impair airway protection. Any hemodynamic changes observed were modest and transient. CONCLUSIONS: FOB-BAL, under NIV and TCI with propofol, is feasible and safe in nonintubated patients with ARF. The TCI of propofol during FOB-BAL reduces patient discomfort with no significant adverse effects. PMID- 21983628 TI - Predicting the success of non-invasive ventilation in preventing intubation and re-intubation in the paediatric intensive care unit. AB - PURPOSE: To determine whether physiological parameters and underlying condition can be used to predict which patients can be managed successfully on non-invasive ventilation (NIV). METHODS: Review of case notes and computerised data of every paediatric intensive care unit (PICU) admission over 7 years where NIV was commenced. Data immediately prior to commencing NIV and 2 h after its establishment was collected. Univariable and multivariable statistical analysis was performed to compare variables. RESULTS: Eighty-three patients commenced NIV attempting to avoid intubation and 64% succeeded. Those who failed required a higher FiO2 (0.56 vs. 0.47, p = 0.038), had higher respiratory rates (53.3 vs. 40.3 breaths/min, p = 0.012) and lower pH (7.26 vs. 7.34, p = 0.032) before NIV and higher FiO2 after NIV commenced (0.54 vs. 0.43, p = 0.009). Those with a respiratory diagnosis were more likely to be successful. Patients with oncologic disease, particularly if septic, were less likely to avoid intubation using NIV. Multivariable models showed that after adjustment for mode of NIV and underlying diagnosis, respiratory rate before NIV was an independent predictor of success [adjusted odds ratio (OR) 0.95 (0.91, 0.99), p = 0.01]. Eighty patients were extubated to NIV but 15 required re-intubation. Those re-intubated had a higher systolic blood pressure (104 vs. 77.9 mmHg, p = 0.001) and diastolic blood pressure (64.5 vs. 54.1 mmHg, p = 0.0037) after extubation. Multivariable models showed that systolic blood pressure 2 h after extubation was independently associated with outcome [adjusted OR 0.96 (0.93, 0.99), p = 0.007]. CONCLUSIONS: Parameters relating to respiratory and cardiovascular status can determine which patients will successfully avoid intubation or re-intubation when placed on NIV. Underlying disease and reason for admission should be considered when predicting the outcome of NIV. PMID- 21983629 TI - A new blue-shifted luciferase from the Brazilian Amydetes fanestratus (Coleoptera: Lampyridae) firefly: molecular evolution and structural/functional properties. AB - Firefly luciferases usually produce bioluminescence in the yellow-green region, with colors in the green and yellow-orange extremes of the spectrum being less common. Several firefly luciferases have already been cloned and sequenced, and site-directed mutagenesis studies have already identified important regions and residues for bioluminescence colors. However the structural determinants and mechanisms of bioluminescence colors turned out to be elusive, mainly when comparing luciferases with a high degree of divergence. Thus comparison of more similar luciferases producing colors in the two extremes of the spectrum could be revealing. The South-American fauna of fireflies remains largely unstudied, with some unique taxa that are not found anywhere else in the world and that produce a wide range of bioluminescence colors. Among them, fireflies of the genus Amydetes are especially interesting because its taxonomical status as an independent subfamily or as a tribe is not yet solved, and because they usually produce a continuous bright blue-shifted bioluminescence. In this work we cloned the cDNA for the luciferase of the Atlantic rain forest Amydetes fanestratus firefly, which is found near Sorocaba municipality (Sao Paulo, Brazil). Despite showing a higher degree of identity with the South-American Cratomorphus, the European Lampyris and the Asiatic Pyrocoelia, phylogenetical analysis of the luciferase sequence support the inclusion of Amydetes as an independent subfamily. Amydetes luciferase displays one of the most blue-shifted emission spectra (lambda(max) = 538 nm) among beetle luciferases, with lower pH-sensitivity and higher affinity for ATP when compared to other luciferases, making this luciferase attractive for sensitive ATP and reporter assays. PMID- 21983630 TI - Stress, anxiety and depression: toward new treatment strategies. PMID- 21983631 TI - Significant coronary stenosis detected by coronary computed angiography in asymptomatic HIV infected subjects. AB - OBJECTIVES: increased incidence of acute coronary events, high rate of abnormal surrogate markers of atherosclerosis and increased amount of coronary calcium have been described in HIV infected population. To expand knowledge on coronary artery disease (CAD) in HIV patients, cardiac CT scan was performed in asymptomatic subjects with low cardiovascular (CV) risk. METHODS: A cross sectional study using dual-source CT (MDCT) coronary angiography.was conducted in HIV-infected subjects with the following characteristics: Framingham Risk Score (FRS) <=10, absence of metabolic syndrome, negative echocardiographic and ECG stress-test. A luminal narrowing exceeding 50% was defined as a clinically significant coronary stenosis. Calcium score was quantified using the Agatston Calcium Score method. RESULTS: Fifty-five subjects were enrolled. Significant coronary stenoses, requiring coronary angiography, were found in 16/55 (29.1%). At multivariate analysis older age was the only variable independently associated with the presence of significant luminal narrowing (p = 0.011). CONCLUSIONS: MDCT showed an unexpected, age-associated high rate of significant coronary stenosis in asymptomatic HIV positive subjects with low CV risk. These findings suggest that aggressive screening programs for coronary artery disease may be appropriate in this population; further studies are recommended to assess the appropriateness of MDCT for this purpose. PMID- 21983632 TI - Critical involvement of extracellular ATP acting on P2RX7 purinergic receptors in photoreceptor cell death. AB - Stressed cells release ATP, which participates in neurodegenerative processes through the specific ligation of P2RX7 purinergic receptors. Here, we demonstrate that extracellular ATP and the more specific P2RX7 agonist, 2'- and 3'-O-(4 benzoylbenzoyl)-ATP, both induce photoreceptor cell death when added to primary retinal cell cultures or when injected into the eyes from wild-type mice, but not into the eyes from P2RX7(-/-) mice. Photoreceptor cell death was accompanied by the activation of caspase-8 and -9, translocation of apoptosis-inducing factor from mitochondria to nuclei, and TUNEL-detectable chromatin fragmentation. All hallmarks of photoreceptor apoptosis were prevented by premedication or co application of Brilliant Blue G, a selective P2RX7 antagonist that is already approved for the staining of internal limiting membranes during ocular surgery. ATP release is up-regulated by nutrient starvation in primary retinal cell cultures and seems to be an initializing event that triggers primary and/or secondary cell death via the positive feedback loop on P2RX7. Our results encourage the potential application of Brilliant Blue G as a novel neuroprotective agent in retinal diseases or similar neurodegenerative pathologies linked to excessive extracellular ATP. PMID- 21983633 TI - Transferred antigen-specific T(H)17 but not T(H)1 cells induce crescentic glomerulonephritis in mice. AB - To explore the role of antigen-specific CD4(+) T cells in glomerulonephritis, we administered ovalbumin 323-339 peptide conjugated to glomerular-binding polyclonal antibody and induced disease in RAG1(-/-) mice with CD4(+) T cells from OT2 * RAG1(-/-) mice. These OT2 * RAG1(-/-) mice have a transgenic T-cell receptor specific for this peptide. When CD4(+) T cells were primed in vivo, crescentic glomerulonephritis developed after 21 days in mice given peptide conjugated glomerular-binding antibody but not unconjugated antibody control. We then investigated the relative roles of T(H)1 and T(H)17 cells, using Fab(2) fragments of glomerular-binding antibody to exclude a role for antibody in this model. T cells from OT2 * RAG1(-/-) mice were polarized in vitro, and T(H)1 or T(H)17 cell lines were injected into mice that were also given peptide-conjugated Fab(2) or unconjugated Fab(2) control, giving four experimental groups. After 21 days crescentic glomerulonephritis was seen in mice receiving T(H)17 cells and peptide-conjugated Fab(2) but in none of the other three groups. These results suggest that T(H)17 but not T(H)1 cells can induce crescentic glomerulonephritis. PMID- 21983634 TI - Prokineticin 1 induces inflammatory response in human myometrium: a potential role in initiating term and preterm parturition. AB - The infiltration of human myometrium and cervix with leukocytes and the formation of a pro-inflammatory environment within the uterus have been associated with the initiation of both term and preterm parturition. The mechanism regulating the onset of this pro-inflammatory cascade is not fully elucidated. We demonstrate that prokineticin 1 (PROK1) is up-regulated in human myometrium and placenta during labor. The expression of PROK1 receptor remains unchanged during labor and is abundantly expressed in the myometrium. Gene array analysis identified 65 genes up-regulated by PROK1 in human myometrium, mainly cytokines and chemokines, including IL-1beta, chemokine C-C motif ligand 3, and colony-stimulating factor 3. In addition, we demonstrate that PROK1 increases the expression of chemokine C C motif ligand 20, IL-6, IL-8, prostaglandin synthase 2, and prostaglandin E(2) and F(2alpha) secretion. The treatment of myometrial explants with 100 ng/mL of lipopolysaccharide up-regulates the expression of PROK1, PROK1 receptor, and inflammatory mediators. The infection of myometrial explants with lentiviral microRNA targeting PROK1, preceding treatment with lipopolysaccharide, reduces the expression of inflammatory genes. We propose that PROK1 is a novel inflammatory mediator that can contribute to the onset of human parturition at term and partially mediate premature onset of inflammatory pathways during bacterial infection. PMID- 21983635 TI - Expression of the IGF axis is decreased in local prostate cancer but enhanced after benign prostate epithelial differentiation and TGF-beta treatment. AB - The insulin-like growth factor (IGF) axis is a molecular pathway intensively investigated in cancer research. Clinical trials targeting the IGF1 receptor (IGF1R) in different tumors, including prostate cancer, are under way. Although studies on the IGF axis in prostate cancer have already entered into clinical trials, the expression and functional role of the IGF axis in benign prostate and in prostate cancer needs to be better defined. We determined mRNA expression levels of the IGF axis in microdissected tissue specimens of local prostate cancer using quantitative PCR. All members of the IGF axis, including IGF1, IGF2, IGF binding proteins 1 through 6, and insulin receptor, were measured in both the stromal and epithelial compartments of the prostate. IGF1, IGF2, IGF1R, and insulin receptor were down-regulated in local prostate cancer tissue compared with matched benign tissue, suggesting that the IGF axis is not induced during prostate cancer development. Using a new prostate epithelial differentiation model, we demonstrate that the expression of the IGF axis is enhanced during normal prostate epithelial differentiation and regulated by tumor growth factor (TGF)-beta. Our data reveal a functional role of the IGF axis in prostate differentiation, underscoring the importance of the IGF axis in normal development and emphasizing the importance of accurate target validation before moving to advanced clinical trials. PMID- 21983636 TI - Dissecting molecular events in thyroid neoplasia provides evidence for distinct evolution of follicular thyroid adenoma and carcinoma. AB - Benign hypofunctional cold thyroid nodules (CTNs) are a frequent scintiscan finding and need to be distinguished from thyroid carcinomas. The origin of CTNs with follicular morphologic features is unresolved. The DNA damage response might act as a physiologic barrier, inhibiting the progression of preneoplastic lesions to neoplasia. We investigated the following in hypofunctional follicular adenoma (FA) and follicular thyroid cancer (FTC): i) the mutation rate of frequently activated oncogenes, ii) the activation of DNA damage response checkpoints, and iii) the differential proteomic pattern between FA and FTC. Both FTC and FA, which did not harbor RAS, phosphoinositide-3-kinase, or PAX/peroxisome proliferator activated receptor-gamma mutations, express various proteins in common and others that are more distinctly expressed in FTC rather than in FA or normal thyroid tissue. This finding is in line with the finding of constitutive DNA damage checkpoint activation (p-Chk2, gamma-H2AX) and evidence for replicative stress causing genomic instability (increased cyclin E, retinoblastoma, or E2F1 mRNA expression) in FTC but not FA. We discuss the findings of the increased expression of translationally controlled tumor protein, phosphatase 2A inhibitor, and DJ-1 in FTC compared with FA identified by proteomics and their potential implication in follicular thyroid carcinogenesis. Our present findings argue for the definition of FA as a truly benign entity and against progressive development of FA to FTC. PMID- 21983637 TI - Apelin attenuates UVB-induced edema and inflammation by promoting vessel function. AB - Apelin, the ligand of the G protein-coupled receptor APJ, is involved in the regulation of cardiovascular functions, fluid homeostasis, and vessel formation. Recent reports indicate that apelin secreted from endothelial cells mediates APJ regulation of blood vessel caliber size; however, the function of apelin in lymphatic vessels is unclear. Here we report that APJ was expressed by human lymphatic endothelial cells and that apelin induced migration and cord formation of lymphatic endothelial cells dose-dependently in vitro. Furthermore, permeability assays demonstrated that apelin stabilizes lymphatic endothelial cells. In vivo, transgenic mice harboring apelin under the control of keratin 14 (K14-apelin) exhibited attenuated UVB-induced edema and a decreased number of CD11b-positive macrophages. Moreover, activation of apelin/APJ signaling inhibited UVB-induced enlargement of lymphatic and blood vessels. Finally, K14 apelin mice blocked the hyperpermeability of lymphatic vessels in inflamed skin. These results indicate that apelin plays a functional role in the stabilization of lymphatic vessels in inflamed tissues and that apelin might be a suitable target for prevention of UVB-induced inflammation. PMID- 21983640 TI - Soil warming alters nitrogen cycling in a New England forest: implications for ecosystem function and structure. AB - Global climate change is expected to affect terrestrial ecosystems in a variety of ways. Some of the more well-studied effects include the biogeochemical feedbacks to the climate system that can either increase or decrease the atmospheric load of greenhouse gases such as carbon dioxide and nitrous oxide. Less well-studied are the effects of climate change on the linkages between soil and plant processes. Here, we report the effects of soil warming on these linkages observed in a large field manipulation of a deciduous forest in southern New England, USA, where soil was continuously warmed 5 degrees C above ambient for 7 years. Over this period, we have observed significant changes to the nitrogen cycle that have the potential to affect tree species composition in the long term. Since the start of the experiment, we have documented a 45% average annual increase in net nitrogen mineralization and a three-fold increase in nitrification such that in years 5 through 7, 25% of the nitrogen mineralized is then nitrified. The warming-induced increase of available nitrogen resulted in increases in the foliar nitrogen content and the relative growth rate of trees in the warmed area. Acer rubrum (red maple) trees have responded the most after 7 years of warming, with the greatest increases in both foliar nitrogen content and relative growth rates. Our study suggests that considering species-specific responses to increases in nitrogen availability and changes in nitrogen form is important in predicting future forest composition and feedbacks to the climate system. PMID- 21983639 TI - Stand- and tree-level determinants of the drought response of Scots pine radial growth. AB - Characterizing the responses of key tree species to extreme climatic events may provide important information for predicting future forest responses to increased climatic variability. Here we aimed at determining which tree- and stand-level attributes were more closely associated with the effect of a severe drought on the radial growth of Scots pine, both in terms of immediate impact and recovery after the drought event. Our dataset included tree-ring series from 393 plots located close to the dry limit of the species range. Time series analysis and mixed-effects models were used to study the growth of each tree and its detailed response to a severe drought event that occurred in 1986. Our results showed that the radial growth responses of Scots pine were determined primarily by tree-level characteristics, such as age and previous growth rate, and secondarily by stand basal area and species richness, whereas local climate had a relatively minor effect. Fast-growing trees were more severely affected by the drought and retained proportionally lower growth rates up to three years after the episode. In absolute terms, however, fast-growing trees performed better both during and after the event. Older trees were found to be less resilient to drought. The effect of stand basal area and species richness indicated that competition for resources worsened the effects of drought, and suggested that the effect of interspecific competition may be particularly detrimental during the drought year. PMID- 21983638 TI - beta-Catenin and K-RAS synergize to form primitive renal epithelial tumors with features of epithelial Wilms' tumors. AB - Wilms' tumor (WT) is the most common childhood renal cancer. Although mutations in known tumor-associated genes (WT1, WTX, and CATNB) occur only in a third of tumors, many tumors show evidence of activated beta-catenin-dependent Wnt signaling, but the molecular mechanism by which this occurs is unknown. A key obstacle to understanding the pathogenesis of WT is the paucity of mouse models that recapitulate its features in humans. Herein, we describe a transgenic mouse model of primitive renal epithelial neoplasms that have high penetrance and mimic the epithelial component of human WT. Introduction of a stabilizing beta-catenin mutation restricted to the kidney is sufficient to induce primitive renal epithelial tumors; however, when compounded with activation of K-RAS, the mice develop large, bilateral, metastatic, multifocal primitive renal epithelial tumors that have the histologic and staining characteristics of the epithelial component of human WT. These highly malignant tumors have increased activation of the phosphatidylinositol 3-kinase-AKT and extracellular signal-regulated kinase pathways, increased expression of total and nuclear beta-catenin, and increased downstream targets of this pathway, such as c-Myc and survivin. Thus, we developed a novel mouse model in which activated K-RAS synergizes with canonical Wnt/beta-catenin signaling to form metastatic primitive renal epithelial tumors that mimic the epithelial component of human WT. PMID- 21983641 TI - Microbiology of the phyllosphere: a playground for testing ecological concepts. AB - Many concepts and theories in ecology are highly debated, because it is often difficult to design decisive tests with sufficient replicates. Examples include biodiversity theories, succession concepts, invasion theories, coexistence theories, and concepts of life history strategies. Microbiological tests of ecological concepts are rapidly accumulating, but have yet to tap into their full potential to complement traditional macroecological theories. Taking the example of microbial communities on leaf surfaces (i.e. the phyllosphere), we show that most explorations of ecological concepts in this field of microbiology focus on autecology and population ecology, while community ecology remains understudied. Notable exceptions are first tests of the island biogeography theory and of biodiversity theories. Here, the phyllosphere provides the unique opportunity to set up replicated experiments, potentially moving fields such as biogeography, macroecology, and landscape ecology beyond theoretical and observational evidence. Future approaches should take advantage of the great range of spatial scales offered by the leaf surface by iteratively linking laboratory experiments with spatial simulation models. PMID- 21983642 TI - Effects of taurochenodeoxycholic acid on adjuvant arthritis in rats. AB - Taurochenodeoxycholic acid (TCDCA) is one of the main bioactive substances of animals' bile acid. In this study, we aimed to investigate the anti-arthritic effects and potential mechanism of TCDCA on adjuvant arthritis (AA) in rats. Freund's complete adjuvant (FCA) was used to induce AA in rats. Paw swelling, index of thymus and spleen and body weight growth rate were measured, and polyarthritis index and radiologic changes were observed. The production of TNF alpha, IL-1beta, IL-6 and IL-10 was detected by ELISA in serum and synoviocytes. mRNA expression of TNF-alpha, IL-1beta, IL-6 and IL-10 was determined by real time RT-PCR in synovium tissue and synoviocytes. In both prophylactic and therapeutic treatment, TCDCA significantly suppressed paw swelling and polyarthritis index, increased the loss body weight and index of thymus and spleen, and amended radiologic changes in AA rats. The overproduction and mRNA expression of TNF-alpha, IL-1beta and IL-6 were remarkably suppressed in serum and synovium tissue of all TCDCA-treated rats, however, IL-10 was markedly increased in prophylactic treatment. In a definite concentration ranging from 300 MUg/mL to 500 MUg/mL, TCDCA showed marked inhibition in the overproduction and mRNA expression of TNF-alpha, IL-1beta and IL-6 in synoviocytes in a concentration-dependent manner, but opposite action on IL-10. In conclusion, treatment with TCDCA confers a good anti-adjuvant arthritis activity in rats, which its reparative effects could be mediated via reduction of the protein and mRNA expression of TNF-alpha, IL-1beta and IL-6, and augment of IL-10 in rats. PMID- 21983643 TI - Anti-inflammatory effect of novel andrographolide derivatives through inhibition of NO and PGE2 production. AB - Andrographolide (1) is a major diterpene lactone exhibiting anti-inflammatory effects and is found in the plant Andrographis paniculata (Burm. f) Nees, which is widely used in Traditional Chinese Medicine. Synthesis of more effective drugs from andrographolide is very interesting and can prove to be highly useful. In this study, we investigated the anti-inflammatory effects of andrographolide and its derivatives (compounds 2-6) through dimethylbenzene-induced ear edema in mice. Substances under study were administrated intragastrically and the structure-activity relationship was analyzed. Results showed that compounds 5 and 6 significantly inhibited ear edema compared with compound 1 (p<0.05), indicating that the introduction of p-Chlorobenzylidene to C-15 of compound 2 enhances the anti-inflammatory effect. Moreover, compound 6 exhibited the strongest anti inflammatory effect against ear edema in mice (79.4%; 1.35 mmol/kg, ig) and paw edema in rats (50.4%; 0.90 mmol/kg, ig). In addition, compound 6 significantly (p<0.05) inhibited granuloma formation and reduced the increase in vascular permeability induced by peritoneal injection of 0.6% acetic acid solution in mice. Findings indicate that compound 6 exerts its enhanced anti-inflammatory effects by decreasing serum iNOS activity, NO production, and PGE(2) production. PMID- 21983644 TI - Dose conversion coefficients for monoenergetic electrons incident on a realistic human eye model with different lens cell populations. AB - The radiation-induced posterior subcapsular cataract has long been generally accepted to be a deterministic effect that does not occur at doses below a threshold of at least 2 Gy. Recent epidemiological studies indicate that the threshold for cataract induction may be much lower or that there may be no threshold at all. A thorough study of this subject requires more accurate dose estimates for the eye lens than those available in ICRP Publication 74. Eye lens absorbed dose per unit fluence conversion coefficients for electron irradiation were calculated using a geometrical model of the eye that takes into account different cell populations of the lens epithelium, together with the MCNPX Monte Carlo radiation transport code package. For the cell population most sensitive to ionizing radiation-the germinative cells-absorbed dose per unit fluence conversion coefficients were determined that are up to a factor of 4.8 higher than the mean eye lens absorbed dose conversion coefficients for electron energies below 2 MeV. Comparison of the results with previously published values for a slightly different eye model showed generally good agreement for all electron energies. Finally, the influence of individual anatomical variability was quantified by positioning the lens at various depths below the cornea. A depth difference of 2 mm between the shallowest and the deepest location of the germinative zone can lead to a difference between the resulting absorbed doses of up to nearly a factor of 5000 for electron energy of 0.7 MeV. PMID- 21983645 TI - Lack of agreement between gross visual and histological assessment of burn reepithelialization in a porcine burn model. AB - One of the most important and earliest measures of burn healing is wound reepithelialization. Reepithelialization is a vital determinant of wound infection and scarring. Reepithelialization is generally based on gross visual assessment; however, histological assessment remains the criterion standard. We hypothesized that there would be poor agreement (r < .4) between gross visual and histological assessments of burn reepithelialization in a porcine model. The study design was prospective observational using three anesthetized female pigs (20-25 kg). Forty-eight 2.5- * 2.5-cm burns were created on the flanks of pig's using an aluminum bar (150 g) preheated to 80 degrees C for 20 seconds. Burns were treated with an occlusive or antimicrobial dressing and photographed at day 10 for determination of gross percentage reepithelialization in a 1-cm diameter circle in the center of the burn by two experienced clinicians masked to each other's measurements. A 10-mm full-thickness punch biopsy was taken from the center of the burns and evaluated by a board-certified dermatopathologist masked to clinical assessments. One clinician and the dermatopathologist repeated the assessments 1 month apart. The outcome was percentage wound reepithelialization at 10 days. The criterion standard was the histological assessment. Intraobserver and interobserver agreements were calculated with Pearson's correlation coefficients. A coefficient less than .4 was considered poor. Sixteen burns were created on each of three animals. Six wounds were excluded because of the presence of a thick eschar covering the burn, making the gross determination of reepithelialization impossible. Intraobserver agreement for histological reepithelialization was 0.96 (P < .001). Intraobserver agreement for gross visual assessment of reepithelialization was 0.75 (P < .001). Interobserver agreement for gross visual assessment of reepithelialization was 0.60 (P < .001). The agreement between gross visual and histological assessment of burn reepithelialization was -0.25. Although there was a good interobserver agreement for gross visual assessments, there was a poor agreement between gross visual and histological assessments of burn reepithelialization. Care should be used when determining burn reepithelialization based on gross visual assessments alone. PMID- 21983646 TI - Increasing the options for management of large and complex chronic wounds with a scalable, closed-system dressing for maggot therapy. AB - As reconstructive specialists, burn surgeons are often involved in managing large wounds of various etiologies. Such wounds can pose a management challenge, especially if they are chronic or occur in the setting of critical illness or multiple medical comorbidities. Medical maggots are an effective, selective, and low-risk method for wound debridement. However, their use in large and geometrically complex wounds is limited by the lack of scalability in currently available dressings, which are appropriate for smaller wounds but become cumbersome and ineffective in larger ones. This report describes a novel dressing designed for application of maggot debridement therapy in large and complex wounds. The authors then discuss how use of this dressing may create new management strategies for such wounds by allowing maggots to mechanically debride big, infected wounds. They describe the construction of a maggot containment dressing based on modified components from a negative pressure wound therapy system and provide a case report highlighting its successful clinical use in a large contaminated chronic wound resulting from Fournier's gangrene. In the case described, the novel dressing provided scalability, containment of maggots, control of secretions, and ease of use. The dressing created an environment suitable for maggot survival and allowed effective debridement of a heavily contaminated groin wound. The novel dressing described is shown to function appropriately, allowing controlled use of maggots for effective debridement of large, irregular wounds. Facilitating the use of maggots in such wounds may broaden the algorithm for their management. PMID- 21983647 TI - Development of a burn prevention teaching tool for Amish children. AB - Although there are inherent risks for burn injury associated with the Amish lifestyle, burn prevention is not taught in Amish schools. The purpose of this study was to develop a burn prevention teaching tool for Amish children. An anonymous parental survey was designed to explore the content and acceptability of a teaching tool within an Old Order Amish community. After institutional review board approval, the Amish teacher distributed surveys to 16 families of the 30 children attending the one-room school. Fourteen (88%) of the families responded to identify these burn risks in and around their homes, barns, and shops: lighters, wood and coal stoves, kerosene heaters, gasoline-powered engines, and hot liquids used for canning, butchering, mopping, washing clothes, and making lye soap. All respondents were in favor of teaching familiar safety precautions, fire escape plans, burn first aid, and emergency care to the children. There was some minor objection to more modern devices such as bath tub thermometers (25%), fire extinguishers (19%), and smoke detectors (6%). The teacher was interested in a magnetic teaching board depicting Amish children and typical objects in their home environment. Movable pieces could afford the opportunity to identify hazards and to rearrange them for a safer situation. This survey served to introduce burn prevention to one Amish community and to develop an appropriate teaching tool for the school. It is anticipated that community participation would support its acceptance and eventual utilization within this tenaciously traditional culture. PMID- 21983648 TI - The ABC daycare disaster of Hermosillo, Mexico. AB - On June 5, 2009, the ABC Daycare facility in Hermosillo, Mexico, caught on fire with an estimated 142 children and 6 adult caregivers inside. The purpose of this article is to describe the factors contributing to the disaster including care of the survivors, tertiary burn center triage, patient transport, and treatment for this international mass casualty event. Finally, the results of an investigation performed by the Mexican Government are reviewed. A summary of the Mexican Government's investigation of the circumstances of fire and an examination of prevention lapses in other Mexican daycare centers was obtained from their public Web site. The demographic and clinical characteristics of the children transported to the burn center were obtained from the patients' medical records and transport data sheets. The ABC Daycare had many fire safety breaches that contributed to the severity of the tragedy. Twenty-nine children died at the scene and more than 35 children were hospitalized throughout Mexico. A total of 12 children were transported to two Shriners Hospitals, 9 to Sacramento, and 3 to Cincinnati. The mean age of patients sent to the Shriners Hospitals was 2.9 +/- 0.16 years (2-4 years), with 5 being male and 7 female. The mean duration between injury and arrival was 9.2 +/- 2.1 days, the burn size was 43.0 +/- 6.8% TBSA (6.5-80%), and there were 3.75 operations per patient. Four had fourth-degree burns requiring finger amputations (2), flaps to cover bone (1), or a through knee amputation (1). Ten patients were admitted to the intensive care unit, and nine patients (seven with inhalation injury) required mechanical ventilation for a mean of 23.6 +/- 10.3 days. All the surviving children were discharged after a mean length of stay of 45.9 +/- 8.7 days. In the first year postinjury, seven children were readmitted a total of 11 times for reconstructive surgery, wound care, or rehabilitation. Ultimately, a total of 49 children died. A review of other daycare centers in Mexico revealed similar safety lapses that could lead to future major disasters. This burn disaster in Hermosillo was potentially preventable with adherence to standard prevention principals. The young age of the victims and the need for an international medical response posed special problems. Prevention efforts need to be improved to prevent future disasters in Mexico. PMID- 21983649 TI - Physiological responses to maximal exercise testing and the modified incremental shuttle walk test in adults after thermal injury: a pilot study. AB - The ongoing hypermetabolic response associated with burn injury contributes significantly to loss of function, morbidity, and mortality. Exercise is strongly recommended to assist recovery and overall functional outcome. To date, there have been limited studies investigating the validity and practicality of both maximal laboratory and field tests in adult burns survivors. The objective of this study was to determine the metabolic and ventilatory response to cardiopulmonary maximal exercise testing (CPET) and the modified shuttle walk test (MSWT) in adult burns patients. Fifteen people (13 male) with a mean TBSA of 38.5% (16.0%) underwent both MSWT and CPET within a 5-day period in random order. The majority of participants demonstrated a normal response to CPET. Two participants with a history of inhalation burns demonstrated a respiratory limitation to exercise with desaturation (91 and 89%) at the end of the CPET, which returned to normal within 2 minutes after exercise. The correlation between VO(2peak) as measured via CPET and distance as measured in MSWT was 0.7. Mean results measured in MSWT for maximal heart rate and perceived exertion scores were lower than those achieved with CPET results: 91 and 88%, respectively. There were no adverse events during both the MSWT and CPET. This study demonstrates that after burn injury, CPET and MSWT can be performed safely in the majority of patients early in the postdischarge rehabilitation period. MSWT is likely to be submaximal at 80 to 90% of CPET results but is easy to replicate and cost effective, thus a viable mechanism for monitoring aerobic capacity. PMID- 21983650 TI - Orthostatic convulsive syncope in a burn patient. AB - Orthostatic convulsive syncope is defined as a decrease in cerebral blood supply resulting in convulsive, seizure-like symptoms. The authors present the first case report of orthostatic convulsive syncope in a burn patient. There are many causes of transient loss of consciousness in patients. An algorithm is presented to aid in the workup and management strategies for this diagnosis. This approach in conjunction with a neurology consult should add in the assessment and treatment of transient loss of consciousness and orthostatic convulsive syncope in a burn patient. PMID- 21983651 TI - Analysis of the microbial community of the biocathode of a hydrogen-producing microbial electrolysis cell. AB - The microbial electrolysis cell (MEC) is a promising system for hydrogen production. Still, expensive catalysts such as platinum are needed for efficient hydrogen evolution at the cathode. Recently, the possibility to use a biocathode as an alternative for platinum was shown. The microorganisms involved in hydrogen evolution in such systems are not yet identified. We analyzed the microbial community of a mixed culture biocathode that was enriched in an MEC bioanode. This biocathode produced 1.1 A m(-2) and 0.63 m3 H2 m(-3) cathode liquid volume per day. The bacterial population consisted of 46% Proteobacteria, 25% Firmicutes, 17% Bacteroidetes, and 12% related to other phyla. The dominant ribotype belonged to the species Desulfovibrio vulgaris. The second major ribotype cluster constituted a novel taxonomic group at the genus level, clustering within uncultured Firmicutes. The third cluster belonged to uncultured Bacteroidetes and grouped in a taxonomic group from which only clones were described before; most of these clones originated from soil samples. The identified novel taxonomic groups developed under environmentally unusual conditions, and this may point to properties that have not been considered before. A pure culture of Desulfovibrio strain G11 inoculated in a cathode of an MEC led to a current development from 0.17 to 0.76 A m(-2) in 9 days, and hydrogen gas formation was observed. On the basis of the known characteristics of Desulfovibrio spp., including its ability to produce hydrogen, we propose a mechanism for hydrogen evolution through Desulfovibrio spp. in a biocathode system. PMID- 21983652 TI - Regulation of heat shock protein 27 phosphorylation during microcystin-LR-induced cytoskeletal reorganization in a human liver cell line. AB - Acute exposure to microcystin-LR (MC-LR) can induce the reorganization or disruption of the cytoskeleton, but proteins or enzymes correlated with this stress response have not been fully identified. Here, we report alterations to HSP27 during MC-LR-induced cytoskeletal reorganization in the human liver cell line HL7702. The cells incubated with MC-LR exhibited the rearrangement of filamentous actins and microtubules. The activity of protein phosphatase 2A was greatly decreased by MC-LR exposure. Furthermore, MC-LR markedly increased the level of HSP27 phosphorylation with the enhanced distribution of phosphorylated HSP27 to the cytoskeleton. To further determine the regulation of MC-LR-induced HSP27 phosphorylation, the activation of the MAPK superfamily was assessed. The result showed phospho-activation of p38 MAPK, JNK and ERK1/2 by MC-LR. Increases in HSP27 phosphorylation were suppressed by pretreating cells with SB203580 or SP600125, which are inhibitors of p38 MAPK or JNK, respectively. These data suggest that phosphorylated HSP27 is involved in cytoskeletal reorganization and is regulated by MAPKs, possibly as a consequence of PP2A inhibition. Moreover, the regulation of HSP27 phosphorylation may be important in MC-LR-induced cytoskeleton reassembly, which may provide helpful insights into the mechanism of MC-LR toxicity. PMID- 21983653 TI - 1,2:3,4-Diepoxybutane in blood of male B6C3F1 mice and male Sprague-Dawley rats exposed to 1,3-butadiene. AB - The important industrial chemical 1,3-butadiene (BD; CAS Registry Number: 106-99 0) is a potent carcinogen in B6C3F1 mice and a weak one in Sprague-Dawley rats. This difference is mainly attributed to the species-specific burden by the metabolically formed 1,2:3,4-diepoxybutane (DEB). However, only limited data exist on the DEB blood burden of rodents at BD concentrations below 100 ppm. Considering this, DEB concentrations were determined in the blood of mice and rats immediately after 6h exposures to various constant concentrations of BD of between about 1 and 1200 ppm. Immediately after its collection, blood was injected into a vial that contained perdeuterated DEB (DEB-D(6)) as internal standard. Plasma samples were prepared and treated with sodium diethyldithiocarbamate that derivatized metabolically produced DEB and DEB-D(6) to their bis(dithiocarbamoyl) esters, which were then analyzed by high performance liquid chromatography coupled with an electrospray ionization tandem mass spectrometer. DEB concentrations in blood versus BD exposure concentrations in air could be described by one-phase exponential association functions. Herewith calculated (+/-)-DEB concentrations in blood increased in mice from 5.4 nmol/l at 1 ppm BD to 1860 nmol/l at 1250 ppm BD and in rats from 1.2 nmol/l at 1 ppm BD to 92 nmol/l at 200 ppm BD, at which exposure concentration 91% of the calculated DEB plateau concentration in rat blood was reached. This information on the species-specific blood burden by the highly mutagenic DEB helps to explain why the carcinogenic potency of BD in rats is low compared to that in mice. PMID- 21983655 TI - Effect of 45 nm silver nanoparticles (AgNPs) upon the smooth muscle of rat trachea: role of nitric oxide. AB - AgNPs have been used to manufacture nanomaterials with new biophysical properties and functions. However, few experimental approaches have been used to assess their potential toxic or beneficial effects on human health, in association with the size, concentration, and biological target. The aim of this work was to evaluate the effects of the AgNPs on the smooth muscle of rat trachea. A single administration of AgNPs did not modify the smooth muscle tone, but, when the trachea rings were pre-treated with acetylcholine (ACh), AgNPs produced a contractile effect. Simultaneous administration of AgNPs and ACh resulted in a slight increase of smooth muscle contractility induced by ACh. AgNPs pretreatment followed by ACh administration showed that AgNPs exerted an important contraction effect induced by ACh after which muscle tone did not return to the basal level. This effect was associated with an increase in the production of nitric oxide (NO). The contractile response of the AgNPs induced by ACh was completely blocked when the rings were incubated, after the ACh but before the AgNPs administration, with 1400 W (NO blocker). The contractile effect was also abolished by atropine, which suggests that AgNPs alter ACh muscarinic receptor signaling. These data also show that AgNPs modify the contractile action of ACh through NO production and possibly induce hyper-reactivity of tracheal smooth muscle. PMID- 21983654 TI - Formaldehyde induces lung inflammation by an oxidant and antioxidant enzymes mediated mechanism in the lung tissue. AB - Formaldehyde (FA) is an indoor and outdoor pollutant widely used by many industries, and its exposure is associated with inflammation and oxidative stress in the airways. Our previous studies have demonstrated the role of reactive oxygen species (ROS) in lung inflammation induced by FA inhalation but did not identify source of the ROS. In the present study, we investigate the effects of FA on the activities and gene expression of glutathione peroxidase (GPX), glutathione reductase (GR), glutathione S-transferase (GST), superoxide dismutase (SOD) 1 and 2, catalase (CAT), nitric oxide synthase (iNOS and cNOS) and cyclooxygenase (COX) 1 and 2. The hypothesized link between NADPH-oxidase, nitric oxide synthase and cyclooxygenase, the lung inflammation after FA inhalation was also investigated. For experiments, male Wistar rats were submitted to FA inhalation (1%, 90 min daily) for 3 consecutive days. The treatments with apocynin and indomethacin before the FA exposure reduced the number of neutrophils recruited into the lung. Moreover, the treatments with apocynin and indomethacin blunted the effect of FA on the generation of IL-1beta, while the treatments with L-NAME and apocynin reduced the generation of IL-6 by lung explants when compared to the untreated group. FA inhalation increased the levels of NO and hydrogen peroxide by BAL cells cultured and the treatments with apocynin and l-NAME reduced these generations. FA inhalation did not modify the activities of GPX, GR, GST and CAT but reduced the activity of SOD when compared to the naive group. Significant increases in SOD-1 and -2, CAT, iNOS, cNOS and COX-1 expression were observed in the FA group compared to the naive group. The treatments with apocynin, indomethacin and L-NAME reduced the gene expression of antioxidant and oxidant enzymes. In conclusion, our results indicate that FA causes a disruption of the physiological balance between oxidant and antioxidant enzymes in lung tissue, most likely favoring the oxidant pathways and thus positively modulating lung inflammation. PMID- 21983656 TI - Neurological complications of foam sclerotherapy: fears and reality. PMID- 21983657 TI - Repeated measurements on individuals. PMID- 21983659 TI - [Not Available]. AB - Zeneker's diverticulum (pharyngeal diverticulum) is a pathological sac-like protrusion of the mucous membrane at the posterior nasopharyngeal wall. Surgical operation is the principal method for the treatment of this rather rare disease. In the present paper, two cases of its successful management by means of laser assisted endoscopic diverticulotomy are described. Both operations were made at the otorhinolaryngological clinic of Sankt-Peterburg State Medical University. Contact laser surgery was for the first time performed for the purpose. PMID- 21983658 TI - Efficacy of Atorvastatin combined with adipose-derived mesenchymal stem cell transplantation on cardiac function in rats with acute myocardial infarction. AB - Mesenchymal stem cells (MSCs) have been extensively applied for the restoration of cardiomyocytes loss after acute myocardial infarction (AMI). However, the optimal therapeutic efficacy of MSCs in ischemic heart diseases has been hampered by their poor survival and low differentiated rates. Therefore, the improvement of MSC survival and differentiated rates is warranted and critical for the efficacy of MSCs in AMI. In this paper, MSCs isolated from rat inguinal fat tissues were termed as adipose-derived mesenchymal stem cells (ASCs), and the fourth passage of ASCs was pre-specified by co-culturing with cardiomyocytes in a transwell system termed as co-ASCs. Fourteen days later, GATA-4 (a transcription factor) and cardiac troponin-I were detected by cellular immunofluorescence. Atorvastatin (Ator group) or vehicle (control group) was administrated for the first 24 h after AMI production in rats. Fourteen days later, inflammatory parameters and cardiac function were evaluated. The other surviving rats were injected with a total of 1 * 10(6) co-ASCs/100 MUl phosphate-buffered saline (PBS), 1*10(6) ASCs/100 MUl PBS, or 100 MUl PBS. Twenty-eight days after cell injection, survival and differentiated rates of transplanted cells and cardiac function were evaluated. The percentage of GATA-4 expression in co-ASCs was 28.5% +/- 5.6% and of cardiac troponin-I was 22.8% +/- 3.2%. Compared with the control group, the number of infiltrating inflammatory cells, myeloperoxidase activity, inflammatory cytokines (VCAM-1, TNF-alpha, Hs-CRP) mRNA expression, and Bax protein expression were significantly reduced in the three Ator groups, accompanied by a significant improvement of Bcl-2 protein expression and cardiac function (P< 0.05). Compared with the Ator2 + ASCs group and Con + co-ASCs group, the number of 4-6-diamidino-2-phenylindole-stained cells and cardiac troponin-I positive transplanted cells, concomitant with cardiac function, were improved most prominently in the Ator3 + co-ASCs group (P< 0.05). Pre-amelioration of the cardiac milieu, in conjunction with pre-specification of ASCs, was beneficial for enhancing ASCs' therapeutic efficacy on cardiac function after AMI. PMID- 21983660 TI - [About the role of chronic viral infection in etiology of proliferative diseases of the ENT organs]. AB - The role of certain viruses (human papilloma virus, Epstein-Barr virus, cytomegalovirus, and herpes virus) in the development and malignization of some pre-cancer conditions in human ENT organs is considered. The results of genetic (with the use of PCR) and histological studies of tissue biopsies and surgical specimens are presented. A total of 107 patients presenting with prolifertaive diseases of ENT organ mucosa were available for tissue sampling along with 30 other patients with histologically verified cancer of the larynx, pharynx, nasal cavity, and paranasal sinuses. The clinical data obtained are discussed. PMID- 21983662 TI - [Anesthesia and respiratory support during endoscopic correction of subcompensated laryngeal stenosis]. AB - A case of successful endoscopic correction of grade II laryngeal stenosis under general anesthesia and respiratory support is reported. High-frequency jet ventilation of the lungs was accomplished through a transtracheally introduced catheter. PMID- 21983661 TI - [The treatment of polypous suppurative rhinosinusitis in the patients presenting with the severe and moderate aspirin triad]. AB - The present study inluded 22 patients presenting either with very severe or moderately severe aspirin triad 17 of whom suffered exacerbation of chronic polypous suppurative rhinosinusitis. The reference group comprised 10 patients with exacerbation of chronic polypous suppurative rhinosinusitis in the absence of concomitant bronchial asthma. The control group included 25 practically healthy subjects having neither chronic somatic diseases nor ENT organ pathology. Conventional otorhinolaryngological examination of the patients was supplemented by cytological studies of the secretion from maxillary sinuses (MS) and inranasal mucosa, measurement of viscosity and pH of MS secretion. It was shown that eosinophil count in the MS secretion was several-fold higher than that in the secretion from nasal cavity mucosa . Polypotomy in the nasal cavity was performed after the preoperative treatment of the patients using sparing procedures, such as laser irradiation and a radiofrequency loop. This approach allowed to reduce the probability of enhancement of bronchial resistance during surgery and in the immediate postoperative period; moreover, it made it possible to continue puncture therapy of patients experiencing exacerbation of the chronic inflammatory process in the maxillary sinuses. PMID- 21983663 TI - [The potential of photodynamic therapy for the treatment of recurrent respiratory papillomatosis]. AB - The problem of recurrent respiratory papillomatosis (RRP) thus far remains unresolved despite a large number of surgical and conservative methods proposed to address it. Photodynamic therapy is an up-to-date tool for the treatment of various neoplasms based on the interaction between the light and a photosensitizing agent (PA) that gives rise to active oxygen species and causes the death of cells. The potential of photodynamic therapy for the treatment of recurrent respiratory papillomatosis remains to be elucidated. A total of 8 seances of photodynamic therapy were undertaken at the Department of Otorhinolaryngology, I.P. Pavlov Sankt-Peterburg State Medical University, during the period between 2006 and 2010 for the treatment of patients with laryngeal and tracheal lesion, two of them under local anesthesia and the remaining ones under general narcosis. Complete and partial regression of the disease was achieved in 2 and 5 cases respectively. One patient failed to benefit from the treatment. Photodynamic therapy was well tolerated by the patients and produced good functional results; none of them developed adverse effects, there were no signs of refractoriness to the treatment. PMID- 21983664 TI - [External granulation otitis]. AB - The authors repot two cases of successful treatment of external granulation otitis. Taken together, the difficulties encountered in diagnostics of this condition, concomitant disorders aggravating pathological changes in the ear, and the malignant clinical course of the disease hamper the adequate management of external granulation otitis. PMID- 21983665 TI - [A case of successful treatment of angioma of the middle and external ear]. AB - A rare form of benign tumour (angioma of the middle and external ear) is described. The preoperative treatment with the use of embolization of the feeding vessel made possible surgical intervention on a practically "dry" operating field. PMID- 21983666 TI - [Two cases of rare atypical localization of the petrosquamosal venous sinusis in the patients presenting with chronic suppurative epitympanitis complicated by cholesteatoma]. AB - The authors report their original observations of rare and difficultto diagnose atypical localization of the petrosquamosal venous sinusis in the patients presenting with chronic suppurative otitis media. Such localization of this sinus was shown to hamper surgical interventions for sanative treatment. PMID- 21983667 TI - [Epidemiological characteristic of the patients presenting with cochleovestibular disorders associated with labyrinthine hydrops]. AB - A total of 1,067 patients complaining of hearing impairment, dizziness, and tympanophony were admitted for the treatment to the Surdological Department of N.I. Pirogov City Clinical Hospital No 1 during the period from 2000 to 2010. As many as 326 (30.5%) patients were preliminarily diagnosed with Meniere's disease based on their medical histories, clinical condition, and the results of questionnaire studies. All of them were subjected to comprehensive audiologic and vestibulogic examination with the use of up-to-date techniques. The data thus obtained allowed to reveal labyrinthine hydrops in 275 (84%) patients. It is concluded that 101 (9.5%) patients presenting with the typical symptoms of Meniere's disease had labyrinthine hydrops. PMID- 21983668 TI - [Morphological and functional changes in the tympanic cavity after its filling with platelet-enriched plasma (an experimental study)]. AB - This experimental study had the objective to estimate the functional state of the sound-conducting system of the middle ear and morphological changes in the tympanic cavity after its filling with platelet-enriched plasma (PEP) obtained by one-step centrifugation of the whole venous blood. The experiments were made on 6 pigs of the Large White breed. Tympanotomy performed under general anesthesia was followed by the introduction of a clot of platelet-enriched plasma into the tympanic cavity. The results of the study indicate that the ventilation function of the pharyngotympanic tube was fully preserved. The PEP clot was completely eliminated from the tympanic cavity within the first month after filling. Neither scars nor adhesions were recorded after the treatment with PEP. The study confirms the beneficial effect of using PEP for the support of the sound conducting structures of the middle ear and stimulation of the regeneration processes after tympanoplasty. PMID- 21983669 TI - [Psychogenic mutation of the voice. Comparative analysis of objective and subjective methods of diagnostics]. AB - The present work had the following objectives: 1) to determine (using a computer program) the fundamental frequency or F0 of the colloquial speech and sonorous cough in the patients with psychogenic mutation of the voice, 2) to obtain subjective (audile) estimation of the quality of their voice, and 3) to develop relevant diagnostic criteria. The study included 10 men aged from 14 to 40 years diagnosed with mutational falsetto (n=5) and incomplete mutation of the voice (n=5). The quality of the voice was independently estimated by three experts. All the patients were exmined using laryngoscopy and laryngostroboscopy. It was demonstrated that mutational falsetto can be diagnosed by subjective estimation of the quality of voice whereas diagnostics of partial voice mutation is possible only with the use of a computer. The author concludes that the fundamental frequency (F0) of sonorous cough is an important diagnostic criterion for psychogenic voice mutation. PMID- 21983670 TI - [Canaloplasty in the rehabilitation of patients presenting with microtia]. AB - A total of 73 patients presenting with grade I, II, and III microtia were given surgical treatment, 35 ones were examined with the use of tympanometry and tonal threshold audiometry; computed tomography (CT) of the temporal bones was applied to examine 33 patients. Special attention in the analysis of CT data was given to 9 major anatomical structures. Indications for the surgical interventions to correct hearing disorders have been developed. PMID- 21983671 TI - [Diagnotsic efficacy of roentgenography and computed tomography of paranasal sinuses in children presenting with mucoviscidosis complicated by chronic rhinosinusitis]. AB - We examined 95 patients with mucoviscidosis admitted to the Russian Children's Clinical Hospital for ENT organ pathology. It was shown that pathology of paranasal sinuses is the most common condition diagnosed in 42% of the children, with chronic polypous sinusitis being its predominant form. A comparative analysis of the efficacy of the main radiodiagnostic techniques (standard roentgenography and computed tomography) in the patients of the study and control groups revealed the characteristic features of pathology of paranasal sinuses associated with mucoviscidosis and resulting from pathogenic processes characteristic of this severe disease. It is concluded that computed tomography is a valuable tool for diagnostics of pathology of paranasal sinuses; moreover, itcan be used to plan the extent of surgical intervention in children presenting with mucoviscidos is complicated by polypous sinusitis. PMID- 21983672 TI - [Endolaryngeal cold-plasma microsurgery for the treatment of benign neoplasms in the larynx and the objective assessment of its functional results]. AB - Endolaryngeal cold-plasma microsurgery for the treatment of benign neoplasms in the larynx used under conditions of high-frequency jet ventilation of the lungs is both a diagnostic tool and a method by which the extent of surgical intervention can be planned. It enables the surgeon to remain in direct contact with the operating field via the tip, to make tangential incisions and probing with a high degree of accuracy. Also, the method ensures bloodless and sterile intervention that induces a less pronounced inflammatory reaction compared with that associated with conventional surgical procedures for the removal of benign laryngeal neoplasms. The methods meet the main criteria for basal surgery; it produces the statistically significant improvement of the voice quality and of dynamic endoscopic characteristics of the larynx. PMID- 21983673 TI - [Long-term clarithromycin therapy in patients with chronic polypous rhinosinusitis]. AB - Article is dedicated to therapeutic effect of long-term therapy clarithromycin in patients with varying severity of chronic polypous rhinosinusitis. The effectiveness of therapy based on monitoring of symptoms and quality of life on a scale of SNOT-20 in an open clinical trial in the treatment in patients with varying degrees of severity of chronic polypous rhino sinusitis with the macrolide Klasid 500 SR was assessed in three months. As a result of investigations, good and excellent effect was observed mainly in patients with mild to moderate disease. Obviously, the duration of therapy should be in cases with severe forms of chronic polypous rhino sinusitismore than 3 months. PMID- 21983674 TI - [The efficacy of application of fenspiride (erespal) for the treatment of exacerbation of bronchial asthma in children]. AB - The objective of the present study was to estimate the efficacy and safety of combination of anti-inflammatory treatment of bronchial asthma (BA) and therapy with erespal. A total of 57 children aged from 6 to 14 years were available for the observation. They presented with mild intermittent (n=27), mild persisting (n=20), and moderately severe (n=10) forms of the disease. The traditional treatment of all the patients was supplemented by daily intake of erespal syrup at a dose of 4 mg/kg b.w. from the first day after admission to the hospital. It is concluded based on the results of the study that the use of erespal reduces the duration of the disease and the time of recovery of bronchial patency; also, it accelerates the process of arterial blood saturation with oxygen. PMID- 21983675 TI - [Clinical efficiency of bacterial lysates used to treat children and adolescents after adenotonsillectomy]. AB - The present study included 58 patients at the age from 12 to 17 years who had undergone adenotonsillectomy under anesthesia. The patients of group 1 (n=28) were additionally treated with IRS 19 and imudon with a view to estimating the influence of bacterial lysates for topical applications on the course of the postoperative period. The control group (group 2) comprised 30 patients. The children of group 1 showed less pronounced reactive changes in the postoperative wound and relatively low bacterial contamination of its surface, mild pain reaction and accelerated regeneration of the injured pharyngeal tissues compared with control subjects. It is concluded that topical application of IRS 19 and imudon bacterial lysates during the postoperative period after adenotonsillectomy produces the well-apparent therapeutic effect and considerably improves the quality of surgical treatment of the patients. PMID- 21983676 TI - [Mucopyocele of the ethmoidal labyrinth]. AB - An isolated affection of a single sinus is a rare occurrence in patients presenting with chronic sinusitis (especially in children). Clinically, chronic ethmoiditis usually has the form of a cattarhal (not infrequently latent) inflammatory process. When the opening of the sinus is closed during a long time, its accumulated contents cause the bone walls to distend and become thinner. A large amount of mucous exudate leads to the development of mucocele (pyocele). A case of mucopyocele in the ethmoidal labyrinth in a 7 year-old girl is reported in conjunction with the results of its treatment. PMID- 21983677 TI - [Recurring dermoid cyst of rare localization]. AB - Dermoid and epidermoid cysts are benign tumours developing from dystonic elements of the epidermal tissue during embryogenesis. They occur in different maxillofacial regions but are especially common at the bottom of the mouth and in the submandibular region; fewer cysts are located in the paotid region. A case of parotid dermoid cyst is reported. PMID- 21983678 TI - [Myxoma of the nasal septum]. PMID- 21983679 TI - [A foreign body in the laryngopharynx with an injured carotid artery that necessitated ligation of the common carotid artery]. PMID- 21983680 TI - N-heterocyclic carbenes as pi*-acceptors in luminescent Re(I) triscarbonyl complexes. AB - Two rhenium(I) carbonyl complexes of the type fac-[Re(CO)(3)(N^C)X] where N^C is an N-heterocyclic carbene [3-butyl-1-(2'-pyridyl)benzimidazolin-2-ylidene] and X is either Cl or Br have been synthesised via an in situ method from [Re(CO)(5)X] and a respective benzimidazolium salt. The complexes have been characterised by (1)H and (13)C NMR, infra-red spectroscopy and in the case of the bromo-complex by a single-crystal X-ray diffraction study. The photophysical properties of the complexes have been investigated, revealing similar phosphorescent emission which was attributed to radiative decay from a (3)MLCT state partially mixed with a (3)LLCT state. However, the analysis of excited state lifetime and quantum yield values revealed distinct photophysical behaviour for the two complexes, which was attributed to the more labile nature of the bromo ligand with respect to the chloro one. The explanation was supported by the time-dependent emission profile change in diluted acetonitrile solutions. PMID- 21983681 TI - Ivy/neurogliaform interneurons coordinate activity in the neurogenic niche. AB - Depolarization by the neurotransmitter GABA regulates adult neurogenesis. We found interneurons of the neurogliaform cell family to be a primary source of GABA for newborn neurons in mouse dentate gyrus. GABAergic depolarization occurred in concert with reduced synaptic inhibition of mature neurons, suggesting that the local circuitry coordinates the activation of new and pre existing cells. PMID- 21983682 TI - Sleep and waking modulate spine turnover in the adolescent mouse cortex. AB - Cortical development involves synaptic formation and elimination. Although synaptogenesis predominates in the early stages and pruning in the later stages, the two processes are thought to happen concurrently. In adults, synaptic strength is modulated by behavioral state, and we asked whether synaptic remodeling may be affected by sleep and waking states. Using two-photon microscopy in adolescent mice, we found that waking results in a net increase in cortical spines, whereas sleep is associated with net spine loss. PMID- 21983685 TI - Host races in Ixodes ricinus, the European vector of Lyme borreliosis. AB - Ixodes ricinus is a European tick that transmits numerous pathogenic agents, including the bacteria that cause Lyme disease (some genospecies of Borrelia burgdorferi sensu lato complex). This tick has been considered as a classic example of an extreme generalist vector. However, host-associations in such vector species are difficult to determine from field observations alone and recent work suggests that host specificity may be more frequent in ticks than previously thought. The presence of host-associated vector groups can significantly alter the circulation and evolutionary pathway of associated pathogens. In this paper, we explicitly test for host-associated genetic structure in I. ricinus. We analyzed genetic variability at 11 microsatellite markers in a large sample of ticks collected directly from trapped wild animals (birds, rodents, lizards, wild boar and roe deer) at five sites in Western and Central Europe. We found significant levels of genetic structure both among host individuals and among host types within local populations, suggesting that host use is not random in I. ricinus. These results help explain previous patterns of structure found in off-host tick samples, along with epidemiological observations of Lyme disease. PMID- 21983684 TI - How unrealistic optimism is maintained in the face of reality. AB - Unrealistic optimism is a pervasive human trait that influences domains ranging from personal relationships to politics and finance. How people maintain unrealistic optimism, despite frequently encountering information that challenges those biased beliefs, is unknown. We examined this question and found a marked asymmetry in belief updating. Participants updated their beliefs more in response to information that was better than expected than to information that was worse. This selectivity was mediated by a relative failure to code for errors that should reduce optimism. Distinct regions of the prefrontal cortex tracked estimation errors when those called for positive update, both in individuals who scored high and low on trait optimism. However, highly optimistic individuals exhibited reduced tracking of estimation errors that called for negative update in right inferior prefrontal gyrus. These findings indicate that optimism is tied to a selective update failure and diminished neural coding of undesirable information regarding the future. PMID- 21983683 TI - Bidirectional plasticity of calcium-permeable AMPA receptors in oligodendrocyte lineage cells. AB - Oligodendrocyte precursor cells (OPCs), a major glial cell type that gives rise to myelinating oligodendrocytes in the CNS, express calcium-permeable AMPA receptors (CP-AMPARs). Although CP-AMPARs are important for OPC proliferation and neuron-glia signaling, they render OPCs susceptible to ischemic damage in early development. We identified factors controlling the dynamic regulation of AMPAR subtypes in OPCs from rat optic nerve and mouse cerebellar cortex. We found that activation of group 1 mGluRs drove an increase in the proportion of CP-AMPARs, reflected by an increase in single-channel conductance and inward rectification. This plasticity required the elevation of intracellular calcium and used PI3K, PICK-1 and the JNK pathway. In white matter, neurons and astrocytes release both ATP and glutamate. Unexpectedly, activation of purinergic receptors in OPCs decreased CP-AMPAR expression, suggesting a capacity for homeostatic regulation. Finally, we found that stargazin-related transmembrane AMPAR regulatory proteins, which are critical for AMPAR surface expression in neurons, regulate CP-AMPAR plasticity in OPCs. PMID- 21983686 TI - Analyzing the genetic diversity of teschoviruses in Spanish pig populations using complete VP1 sequences. AB - Porcine teschoviruses (PTVs) have been previously shown to be the most abundant cytopathic viruses found in swine feces. In the present study, the diversity of PTVs was studied, using PTV isolates collected between 2004 and 2009 in a wide territory in Spain. In order to characterize genetically the isolates, phylogeny reconstructions were made using maximum likelihood and Bayesian inference methods, based on the 1D (VP1) gene, and including sequences available in public databases. The phylogenetic trees obtained indicated that PTVs present 12 main lineages, 11 corresponding to the PTV serotypes described to date, and one lineage distinct from the rest. The geographic distribution of the different lineages does not seem to be strongly associated to particular territories, and co-circulation of multiple lineages was found in the same geographic areas. Nevertheless, some spatial structuring of the viral populations studied is indicated by the differences found between Spanish samples with respect to other European countries. A coalescent-based approach indicated that mutation may have been the main factor in originating the genetic diversity observed in the VP1 gene region. This study revealed a high diversity of teschoviruses circulating in the pig populations studied, and showed that molecular analysis of the complete VP1 protein is a suitable method for the identification of members of the porcine teschovirus group. However, further analyses are needed to clarify the geographical structuring of the different PTV populations. PMID- 21983687 TI - A naturally occurring cowpox virus with an ectromelia virus A-type inclusion protein gene displays atypical A-type inclusions. AB - Human orthopoxvirus (OPV) infections in Europe are usually caused by cowpox virus (CPXV). The genetic heterogeneity of CPXVs may in part be due to recombination with other OPV species. We describe the characterization of an atypical CPXV (CPXV-No-H2) isolated from a human patient in Norway. CPXV-No-H2 was characterized on the basis of A-type inclusion (ATI) phenotype as well as the DNA region containing the p4c and atip open reading frames. CPXV-No-H2 produced atypical V(+/) ATI, in which virions are on the surface of ATI but not within the ATI matrix. Phylogenetic analysis showed that the atip gene of CPXV-No-H2 clustered closely with that of ectromelia virus (ECTV) with a bootstrap support of 100% whereas its p4c gene is diverged compared to homologues in other OPV species. By recombination analysis we identified a putative crossover event at nucleotide 147, downstream the start of the atip gene. Our results suggest that CPXV-No-H2 originated from a recombination between CPXV and ECTV. Our findings are relevant to the evolution of OPVs. PMID- 21983688 TI - The influence of distributional kinetics into a peripheral compartment on the pharmacokinetics of substrate partitioning between blood and brain tissue. AB - Development of CNS-targeted agents often focuses on identifying compounds with "good" CNS exposure (brain-to-blood partitioning >1). Some compounds undergoing enterohepatic recycling (ER) evidence a partition coefficient, K (p,brain) (expressed as C (brain) /C (plasma)), that exceeds and then decreases to (i.e., overshoots) a plateau (distribution equilibrium) value, rather than increasing monotonically to this value. This study tested the hypothesis that overshoot in K (p,brain) is due to substrate residence in a peripheral compartment. Simulations were based on a 3-compartment model with distributional clearances between central and brain (CL (br)) and central and peripheral (CL (d)) compartments and irreversible clearance from the central compartment (CL). Parameters were varied to investigate the relationship between overshoot and peripheral compartment volume (V (p)), and how this relationship was modulated by other model parameters. Overshoot magnitude and duration were characterized as peak C (brain)/C (plasma) relative to the plateau value (%OS) and time to reach plateau (TRP). Except for systems with high CL (d), increasing V (p) increased TRP and %OS. Increasing brain (V (br)) or central (V (c)) distribution volumes eliminated V (p)-related OS. Parallel increases in all clearances shortened TRP, but did not alter %OS. Increasing either CL or CL (d) individually increased %OS related to V (p), while increasing CL (br) decreased %OS. Under realistic peripheral distribution scenarios, C (brain)/C (plasma) may overshoot substantially K (p,brain) at distribution equilibrium. This observation suggests potential for erroneous assessment of brain disposition, particularly for compounds which exhibit a large apparent V (p), and emphasizes the need for complete understanding of distributional kinetics when evaluating brain uptake. PMID- 21983689 TI - PGC-1 family coactivators and cell fate: roles in cancer, neurodegeneration, cardiovascular disease and retrograde mitochondria-nucleus signalling. AB - Over the past two decades, a complex nuclear transcriptional machinery controlling mitochondrial biogenesis and function has been described. Central to this network are the PGC-1 family coactivators, characterised as master regulators of mitochondrial biogenesis. Recent literature has identified a broader role for PGC-1 coactivators in both cell death and cellular adaptation under conditions of stress, here reviewed in the context of the pathology associated with cancer, neurodegeneration and cardiovascular disease. Moreover, we propose that these studies also imply a novel conceptual framework on the general role of mitochondrial dysfunction in disease. It is now well established that the complex nuclear transcriptional control of mitochondrial biogenesis allows for adaptation of mitochondrial mass and function to environmental conditions. On the other hand, it has also been suggested that mitochondria alter their function according to prevailing cellular energetic requirements and thus function as sensors that generate signals to adjust fundamental cellular processes through a retrograde mitochondria-nucleus signalling pathway. Therefore, altered mitochondrial function can affect cell fate not only directly by modifying cellular energy levels or redox state, but also indirectly, by altering nuclear transcriptional patterns. The current literature on such retrograde signalling in both yeast and mammalian cells is thus reviewed, with an outlook on its potential contribution to disease through the regulation of PGC-1 family coactivators. We propose that further investigation of these pathways will lead to the identification of novel pharmacological targets and treatment strategies to combat disease. PMID- 21983690 TI - The role of mitochondria in direct cell-to-cell connection dependent rescue of postischemic cardiomyoblasts. AB - In this in vitro study we induced ischemic injury on H9c2 rat cardiomyoblasts using the oxygen-glucose deprivation model (OGD). We monitored if the addition of healthy or mitochondria-depleted cells can save OGD treated cells from post ischemic injury. We were able to significantly improve the surviving cell number of oxidatively damaged H9c2 cells by the addition of healthy cells to the culture. On the contrary, cells with disturbed mitochondria did not increase the number of surviving cells. High-resolution confocal time-lapse imaging also proved that mitochondria are drifting from cell-to-cell through tunneling membrane bridges, however, they do not get into the cytoplasm of the other cell. We conclude that addition of healthy cells to severly injured post-ischemic cardiomyoblasts can rescue them from death during the first 24h after reoxigenation. Grafted cells must maintain their mitochondria in an actively respiring state, and although cell contact is required for the mechanism, neither cell fusion nor organelle transfer occurs. This novel mechanism opens a new possiblity for cell-based cardiac repair in ischemic heart disease. PMID- 21983691 TI - Parkinson's disease-like neuromuscular defects occur in prenyl diphosphate synthase subunit 2 (Pdss2) mutant mice. AB - The Pdss2 gene product is needed for the isoprenylation of benzoquinone to generate coenzyme Q (CoQ). A fatal kidney disease occurs in mice that are homozygous for a missense mutation in Pdss2, which can be recapitulated in conditional Pdss2 knockouts targeted to glomerular podocytes. We now report that homozygous missense mutants also demonstrate significant neuromuscular deficits, as validated by behavioral and coordination assays, and these deficits are recapitulated in conditional Pdss2 knockouts targeted to dopaminergic neurons. Both conditional knockout and missense mutant mice demonstrate deficiencies in tyrosine hydroxylase-positive neurons in the substantia nigra, implicating a pathology similar to sporadic Parkinson's disease (PD). PMID- 21983692 TI - In the heart or in the head: relationship and cognitive influences on sexual risk among young couples. AB - Few studies examine how relationship factors influence sexual risk. We investigated gender differences of the influence of relationship functioning on sexual risk behavior and sexually transmitted infections (STIs) among 296 young pregnant couples. Compared to women, men were twice as likely to have a concurrent partner, were less likely to intend to be monogamous in the future, had less HIV/STI knowledge and more perceived risk for HIV/STI, negative attitudes and efficacy toward condom use (all P < 0.05). For men, poor relationship functioning related to less intentions to be monogamous, more partner concurrency, worse sexual communication, and more condom use. For women, poor relationship functioning related to worse sexual communication and less condom use. In addition, women who had good relationship functioning and women who had partners with poor relationship functioning were more likely to have an STI. These results demonstrate the need to include heterosexual men and relationship factors in HIV prevention. PMID- 21983693 TI - Estimating HIV incidence and the correlates of recent infection in venue-sampled men who have sex with men in New York City. AB - In a cross-sectional study, MSM aged >=18 years were venue-sampled in New York City in 2008, interviewed, and tested for HIV using oral fluids. Participants who reported testing HIV negative at their last test in the previous 24 months were analyzed (n = 287 of 550 sampled). Those testing positive at the interview were defined as recently infected. HIV incidence was estimated using person-time at risk methods and correlates of recent infection using proportional hazards regression. Thirty-two (11.1%) were recently infected. HIV incidence was 5.67/100 person-years at-risk. Independent correlates included: study recruitment in parks vs. bars, and in other venues vs. bars; black vs. non-black race/ethnicity; and reporting a last sex partner with a positive or unknown vs. negative HIV status. When assay-based methods are not feasible, cross-sectional HIV test results and self-reported HIV testing history and risk factor data can be used to estimate HIV incidence and the correlates of recent infection. PMID- 21983694 TI - Understanding the HIV/AIDS epidemic in transgender women of Lima, Peru: results from a sero-epidemiologic study using respondent driven sampling. AB - In Latin America, transgender women (transwomen or male to female transgenders) have been included in MSM research but without addressing their specific needs in terms of the HIV/AIDS. We present results of the first seroepidemiologic study designed for transwomen in Peru. We conducted a study using respondent driven sampling to recruit transwomen from Lima. Our survey explored sociodemographic characteristics, gender enhancement procedures and sexual behavior. In addition, we conducted laboratory based HIV, genital herpes (HSV2) and syphilis testing. A total of 450 transwomen were recruited between April and July 2009. HIV prevalence was 30%, HSV2: 79% and syphilis: 23%. Sex-work was the main economic activity (64%). Gender enhancement procedures were reported by 70% of the population. Multivariable analysis showed HIV infection to be associated with being older than 35 recent, syphilis infection and HSV2 infection. Transwomen are the group most vulnerable to HIV/AIDS in Peru. PMID- 21983695 TI - The relationship between gender role conflict and condom use among black MSM. AB - Gender role conflict may influence condom use among black MSM. We examined relationships between the Gender Role Conflict Scale (GRCS), social/demographic variables and condom use among 456 black MSM. Higher total GRCS scores did not predict unprotected insertive anal intercourse (UIAI) or unprotected receptive anal intercourse (URAI) with men, but were associated with unprotected vaginal or anal intercourse (UVI/UAI) with women among bisexually active participants (n = 69). Higher perceived HIV risk reduced the likelihood of both UIAI and URAI with men. Internet recruitment venues, sexual discrimination experiences, higher numbers of sex partners and UVI/UAI with women all increased the likelihood of UIAI with men, while education (college/technical school or college degree) was associated with URAI with men. Future sexual health interventions for black MSM should emphasize broader social/demographic and alternative gender role variables with male sexual partners, while traditional GRCS variables may prove useful among those with female sexual partners. PMID- 21983696 TI - Body mass index, depression and sexual transmission risk behaviors among HIV positive MSM. AB - Depression has been shown to be a risk factor for serodiscordant unprotected anal intercourse (SDUAI) in some studies, but not others. Body mass index (BMI) has recently been associated with SDUAI; however, to date, no published study has investigated the interactive effect of depression and BMI on SDUAI. The current study assessed the association between depression, BMI, and SDUAI among HIV positive MSM. Participants were 430 HIV-positive MSM recruited in a Boston community health center where they received primary care. Participants completed audio computer-assisted self interview (ACASI) measures. Objective height and weight and other clinical variables were accessed through participants' electronic medical records. Depression was positively associated with SDUAI. This association was significantly moderated by BMI. Elevated levels of depression were only associated with SDUAI for underweight participants. These findings suggest that underweight, depressed HIV-positive MSM may be particularly likely to engage in SDUAI. PMID- 21983697 TI - Disease progression and characteristics of HIV-infected women with and without a history of criminal justice involvement. AB - Early HIV diagnosis followed by prompt linkage to and consistent retention in HIV related care is important to decrease morbidity and mortality. Progression to AIDS is of particular interest in HIV-positive women with a history of criminal justice-involvement due to their lack of access to care in the community and poor retention in HIV primary care. In this retrospective cohort study, we characterize the risk of developing AIDS among HIV-infected women with and without a history of criminal justice-involvement. Mean time to AIDS diagnosis was longer [123 +/- 3.26 months] for women with no criminal justice-involvement when compared to women who were arrested or who went to prison. Women who were arrested (HR: 1.92, 95% CI: 1.43, 2.58) and women who went to prison (HR: 2.27, 95% CI: 1.52, 3.39) had an increased risk of developing AIDS when compared to women without criminal justice-involvement. PMID- 21983698 TI - Behaviour change counselling for ARV adherence support within primary health care facilities in the Western Cape, South Africa. AB - Health care systems have been described as ideal settings for behaviour change counselling interventions. There is little research evaluating the feasibility of implementing such interventions in routine practice in primary care facilities. We implemented an intervention called Options for Health within routine adherence counselling practice in 20 antiretroviral facilities in Cape Town, South Africa. Lay counsellors were trained to use Options to help clients to optimise ARV adherence and reduce sexual risk behaviour. Counsellors delivered the intervention to 9% of eligible patients over 12 months. Interviews with counsellors revealed barriers to implementation including a lack of counselling space, time pressure and patient resistance to counselling. Counsellors felt that Options was not appropriate for use with all patients and adherence problems, and used parts of the intervention as it suited their needs. Findings revealed weaknesses in the current adherence counselling system that have implications for the feasibility of behaviour change counselling within this context. PMID- 21983699 TI - pH-Driven dynamic stereoinduction: epimerization upon dimerization in rhenium(I) complexes. AB - Stereochemistry at the metal centre in a Re(I) complex can be modified by manipulating the pH: while acidic conditions favour a monomeric system, basic conditions induce a dimerization which concomitantly epimerizes the metal centre. PMID- 21983701 TI - A custom-built PET phantom design for quantitative imaging of printed distributions. AB - This note presents a practical approach to a custom-made design of PET phantoms enabling the use of digital radioactive distributions with high quantitative accuracy and spatial resolution. The phantom design allows planar sources of any radioactivity distribution to be imaged in transaxial and axial (sagittal or coronal) planes. Although the design presented here is specially adapted to the high-resolution research tomograph (HRRT), the presented methods can be adapted to almost any PET scanner. Although the presented phantom design has many advantages, a number of practical issues had to be overcome such as positioning of the printed source, calibration, uniformity and reproducibility of printing. A well counter (WC) was used in the calibration procedure to find the nonlinear relationship between digital voxel intensities and the actual measured radioactive concentrations. Repeated printing together with WC measurements and computed radiography (CR) using phosphor imaging plates (IP) were used to evaluate the reproducibility and uniformity of such printing. Results show satisfactory printing uniformity and reproducibility; however, calibration is dependent on the printing mode and the physical state of the cartridge. As a demonstration of the utility of using printed phantoms, the image resolution and quantitative accuracy of reconstructed HRRT images are assessed. There is very good quantitative agreement in the calibration procedure between HRRT, CR and WC measurements. However, the high resolution of CR and its quantitative accuracy supported by WC measurements made it possible to show the degraded resolution of HRRT brain images caused by the partial-volume effect and the limits of iterative image reconstruction. PMID- 21983700 TI - A new synthetic HDAC inhibitor, MHY218, induces apoptosis or autophagy-related cell death in tamoxifen-resistant MCF-7 breast cancer cells. AB - Acquired resistance to tamoxifen (Tam) is a critical problem in breast cancer therapy. Therefore, new potential strategies for Tam-resistant breast cancer are needed recently. In this study, we synthesized a novel histone deacetylase (HDAC) inhibitor, MHY218, for the development of potent inhibitors of HDAC and evaluated its biological activities by monitoring the anticancer effects in Tam-resistant MCF-7 (TAMR/MCF-7) cells via in vitro and in vivo studies. MHY218 significantly inhibited the proliferation of TAMR/MCF-7 cells in a dose-dependent manner. The total HDAC enzyme activity was significantly inhibited, corresponding with inhibition of acetylated H3 and H4 expression in TAMR/MCF-7 cells. HDAC1, 4, and 6 expression levels were decreased in response to MHY218 treatment. Cell cycle analysis indicated that MHY218 induced G2/M phase cell cycle arrest. As expected, apoptotic cell death was observed in response to MHY218 treatment. Interestingly, levels of beclin-1 and LC3-II, the markers of autophagy, were increased in TAMR/MCF-7 cells treated with MHY218. The efficacy of MHY218 was also compared with that of SAHA in vivo in a xenograft model of nude mice bearing a TAMR/MCF-7 cells. MHY218 (10 mg/kg, twice a week for 21 days) completely inhibited tumor growth and MHY218 markedly inhibited the expression of proliferative cell nuclear antigen (PCNA) in tumor tissue. These results indicate that MHY218 can induce caspase-independent autophagic cell death rather than apoptotic cell death. The MHY218-induced autophagic cell death could be a new strategy in the treatment of Tam-resistant human breast cancer. PMID- 21983702 TI - Differences in fixation stability between spacer plate and plate fixator following high tibial osteotomy. AB - PURPOSE: Since in vivo stability following high tibial osteotomy is unknown, surgeons customize the postoperative rehabilitation to the assumed implant stability, leaving us with numerous rehabilitation protocols. The purpose of the study is to quantify the fixation stability of different open-wedge high tibial osteotomy implants. It is hypothesized that the higher fixation stability of a plate fixator justifies early weight bearing. METHODS: In this prospective 30 subject clinical trial, fixation stability was determined over a 2-year period using radiostereometric analysis (RSA). Patients were assigned to two angle stable osteotomy plates: a spacer plate with 6 postoperative weeks of feather touch weight bearing versus a plate fixator with 2 postoperative weeks of feather touch weight bearing. RESULTS: Postoperative RSA data showed a significant higher lateral translation of the distal tibia and a significantly increased subsidence, varus and internal rotation of the tibial head in the spacer plate compared to the plate fixator group. Weight bearing following spacer plate fixation induced significant micromotion 6 weeks after surgery. Three months after surgery, bone healing was achieved regardless of the used implant. CONCLUSIONS: Early weight bearing is appropriate for plate fixator fixation. The 6-week period of delayed weight bearing following spacer plate fixation is inadequate and should be prolonged presumably up to 8-10 weeks to avoid pseudarthrosis and/or recurrence of varus angulation. LEVEL OF EVIDENCE: Level II, diagnostic study--investigating a diagnostic test. PMID- 21983703 TI - Molecular determinants for substrate selectivity of omega-transaminases. AB - omega-Transaminase (omega-TA) is an industrially important enzyme for production of chiral amines. About 20 (S)-specific omega-TAs known to date show remarkably similar substrate selectivity characterized by stringent steric constraint precluding entry of a substituent larger than an ethyl group in the small binding pocket (S) and dual recognition of an aromatic substituent as well as a carboxylate group in the large pocket (L). The strictly defined substrate selectivity of the available omega-TAs remains a limiting factor in the production of structurally diverse chiral amines. In this work, we cloned, purified, and characterized three new omega-TAs from Ochrobactrum anthropi, Acinetobacter baumannii, and Acetobacter pasteurianus that were identified by a BLASTP search using the previously studied omega-TA from Paracoccus denitrificans. All the new omega-TAs exhibited similar substrate specificity, which led us to explore whether the molecular determinants for the substrate specificity are conserved among the omega-TAs. To this end, key active site residues were identified by docking simulation using the X-ray structure of the omega-TA from Pseudomonas putida. We found that the dual recognition in the L pocket is ascribed to Tyr23, Phe88*, and Tyr152 for hydrophobic interaction and Arg414 for recognition of a carboxylate group. In addition, the docking simulation indicates that Trp60 and Ile262 form the S pocket where the substituent size up to an ethyl group turns out to be sterically allowed. The six key residues were found to be essentially conserved among nine omega-TA sequences, underlying the molecular basis for the high similarity in the substrate selectivity. PMID- 21983704 TI - Intermediate accumulation of metabolites results in a bottleneck for mineralisation of the herbicide metabolite 2,6-dichlorobenzamide (BAM) by Aminobacter spp. AB - Degradation and mineralisation of the groundwater contaminant 2,6-dichloro benzamide (BAM) was investigated in two Aminobacter strains focussing on the induction of BAM degradation and mineralisation and occurrence of intermediate metabolites. The BAM degradation rate was independent of whether the cells were pre-grown in the absence or presence of BAM, thus indicating that the first step in the degradation pathway was constitutively expressed. In contrast, (14)CO(2) production was stimulated when cells were pre-grown in the presence of BAM, suggesting that one or more of the subsequent steps in the degradation pathway were inducible. Accumulation of 2,6-dichlorobenzoate (DCBA) during degradation of BAM demonstrated that the first step involved amidase activity. Mass balance calculations and thin-layer chromatography coupled with autoradiographic detection indicated that degradation of DCBA and at least one unknown metabolite may comprise a bottleneck for BAM mineralisation by Aminobacter spp. The study thus provides novel information about the BAM degradation pathway and points to the involvement of unknown intermediate metabolites in degradation of this important groundwater contaminant. PMID- 21983705 TI - Population dynamics and current-generation mechanisms in cassette-electrode microbial fuel cells. AB - Cassette-electrode microbial fuel cells (CE-MFCs) have been demonstrated useful to treat biomass wastes and recover electric energy from them. In order to reveal electricity-generation mechanisms in CE-MFCs, the present study operated a bench scale reactor (1 l in capacity; approximately 1,000 cm(2) in anode and cathode areas) for treating a high-strength model organic wastewater (comprised of starch, peptone, and fish extract). Approximately 1 month was needed for the bench reactor to attain a stable performance, after which volumetric maximum power densities persisted between 120 and 150 mW/l throughout the experiment (for over 2 months). Temporal increases in the external resistance were found to induce subsequent increases in power outputs. After electric output became stable, electrolyte and anode were sampled from the reactor for evaluating their current-generation abilities; it was estimated that most of current (over 80%) was generated by microbes in the electrolyte. Cyclic voltammetry of an electrolyte supernatant detected several electron shuttles with different standard redox potentials at high concentrations (equivalent to or more than 100 MUM 5-hydroxy-1,4-naphthoquinone). Denaturing gradient gel electrophoresis and quantitative real-time PCR of 16S ribosomal RNA gene fragments showed that bacteria related to the genus Dysgonomonas occurred abundantly in association with the increases in power outputs. These results suggest that mediated electron transfer was the main mechanism for electricity generation in CE-MFC, where high concentration electron shuttles and Dysgonomonas bacteria played important roles. PMID- 21983706 TI - Exopolysaccharide-producing cyanobacteria in heavy metal removal from water: molecular basis and practical applicability of the biosorption process. AB - Microorganisms can remove metals from the surrounding environment with various mechanisms, either as metabolically mediated processes or as a passive adsorption of metals on the charged macromolecules of the cell envelope. Owing to the presence of a large number of negative charges on the external cell layers, exopolysaccharides (EPS)-producing cyanobacteria have been considered very promising as chelating agents for the removal of positively charged heavy metal ions from water solutions, and an increasing number of studies on their use in metal biosorption have been published in recent years. In this review, the attention was mainly focused on the studies aimed at defining the molecular mechanisms of the metal binding to the polysaccharidic exocellular layers. Moreover, the few attempts done in the use of EPS-producing cyanobacteria for metal biosorption at pilot scale and with real wastewaters are here reviewed, discussing the main positive issues and the drawbacks so far emerging from these experiments. PMID- 21983707 TI - Optimized procedure to generate heavy isotope and selenomethionine-labeled proteins for structure determination using Escherichia coli-based expression systems. AB - Generating sufficient quantities of labeled proteins represents a bottleneck in protein structure determination. A simple protocol for producing heavy isotope as well as selenomethionine (Se-Met)-labeled proteins was developed using T7-based Escherichia coli expression systems. The protocol is applicable for generation of single-, double-, and triple-labeled proteins ((15)N, (13)C, and (2)H) in shaker flask cultures. Label incorporation into the target protein reached 99% and 97% for (15)N and (13)C, respectively, and 75% of (non-exchangeable) hydrogen for (2)H labeling. The expression yields and final cell densities (OD600 ~16) were the same as for the production of non-labeled protein. This protocol is also applicable for Se-Met labeling, leading to Se-Met incorporation into the target protein of 70% or 90% using prototrophic or methionine auxotrophic E. coli strains, respectively. PMID- 21983708 TI - Improvement of specific growth rate of Pichia pastoris for effective porcine interferon-alpha production with an on-line model-based glycerol feeding strategy. AB - Effective expression of porcine interferon-alpha (pIFN-alpha) with recombinant Pichia pastoris was conducted in a bench-scale fermentor. The influence of the glycerol feeding strategy on the specific growth rate and protein production was investigated. The traditional DO-stat feeding strategy led to very low cell growth rate resulting in low dry cell weight (DCW) of about 90 g/L during the subsequent induction phase. The previously reported Artificial Neural Network Pattern Recognition (ANNPR) model-based glycerol feeding strategy improved the cell density to 120 g DCW/L, while the specific growth rate decreased from 0.15 to 0.18 to 0.03-0.08 h(-1) during the last 10 h of the glycerol feeding stage leading to a variation of the porcine interferon-alpha production, as the glycerol feeding scheme had a significant effect on the induction phase. This problem was resolved by an improved ANNPR model-based feeding strategy to maintain the specific growth rate above 0.11 h(-1). With this feeding strategy, the pIFN-alpha concentration reached a level of 1.43 g/L, more than 1.5-fold higher than that obtained with the previously adopted feeding strategy. Our results showed that increasing the specific growth rate favored the target protein production and the glycerol feeding methods directly influenced the induction stage. Consequently, higher cell density and specific growth rate as well as effective porcine interferon-alpha production have been achieved by our novel glycerol feeding strategy. PMID- 21983709 TI - Oxidation of arsenite by two beta-proteobacteria isolated from soil. AB - Two heterotrophic As(III)-oxidizing bacteria, SPB-24 and SPB-31 were isolated from garden soil. Based on 16S rRNA gene sequence analysis, strain SPB-24 was closely related to genus Bordetella, and strain SPB-31 was most closely related to genus Achromobacter. Both strains exhibited high As(III) (15 mM for SPB-24 and 40 mM for SPB-31) and As(V) (>300 mM for both strains) resistance. Both strains oxidized 5 mM As(III) in minimal medium with oxidation rate of 554 and 558 MUM h( 1) for SPB-24 and SPB-31, respectively. Washed cells of both strains oxidized As(III) over broad pH and temperature range with optimum pH 6 and temperature 42 degrees C for both strains. The As(III) oxidation kinetic by washed cells showed K (m) and V (max) values of 41.7 MUM and 1,166 MUM h(-1) for SPB-24, 52 MUM and 1,186 MUM h(-1) for SPB-31. In the presence of minimal amount of carbon source, the strains showed high As(III) oxidation rate and high specific arsenite oxidase activity. The ability of strains to resist high concentration of arsenic and oxidize As(III) with highest rates reported so far makes them potential candidates for bioremediation of arsenic-contaminated environment. PMID- 21983710 TI - Characterization and regulation of the 2,3-butanediol pathway in Serratia marcescens. AB - Serratia marcescens has been proved to be a potential strain for industrial 2,3 butanediol production for its high yield, productivity, and other advantages. In this study, the genes slaA, slaB, slaC, and slaR were successfully cloned which were further confirmed to be encoding acetolactate decarboxylase, acetolactate synthase, 2,3-butanediol dehydrogenase, and a LysR-like regulator, respectively. Unlike in Klebsiella sp. or Klebsiella pneumonie and Vibrio sp. or Vibrio cholerae, the gene slaC is separated from other genes. Then it showed that two regulators, SwrR and SlaR, are in charge of this process by exerting effect on the transcription of genes slaA and slaB. By contrast, the expression of gene slaC is unaffected by the two regulators. It means that these two regulators affect the production of 2,3-butanediol by regulating the production of acetoin. Based on these findings, we successfully accelerated the 2,3-butanediol production by inactivation of gene swrR. The obtained results and further investigations should lead to a more suitable fermentation strategy and strain improvement which would be applicable to the industrial production of 2,3 butanediol. PMID- 21983711 TI - Synergistic control of CO2 emissions by fish and nutrients in a humic tropical lake. AB - Using experimental mesocosms, we tested the strength of bottom-up controls by nutrients and top-down controls by an omnivorous fish (Hyphessobrycon bifasciatus; family Characidae), and the interaction between them on the CO(2) partial pressure (pCO(2)) in the surface waters of a tropical humic lake (Lake Cabiunas, Brazil). The experiment included the addition of nutrients and fish to the mesocosms in a factorial design. Overall, persistent CO(2) emissions to the atmosphere, supported by an intense net heterotrophy, were observed in all treatments and replicates over the 6-week study period. The CO(2) efflux (average +/- standard error) integrated over the experiment was similar among the control mesocosms and those receiving only fish or only nutrients (309 +/- 2, 303 +/- 16, and 297 +/- 17 mmol CO(2) m(-2) day(-1), respectively). However, the addition of nutrients in the presence of fish resulted in a high algal biomass and daytime net autotrophy, reducing the CO(2) emissions by 35% (by 193 +/- 7 mmol CO(2) m( 2) day(-1)). These results indicate that high CO(2) emissions persist following the eutrophication of humic waters, but that the magnitude of these emissions might depend on the structure of the food web. In conclusion, fish and nutrients may act in a synergistic manner to modulate persistent CO(2) emissions from tropical humic lakes. PMID- 21983712 TI - Fish mediate high food web connectivity in the lower reaches of a tropical floodplain river. AB - High levels of hydrological connectivity during seasonal flooding provide significant opportunities for movements of fish between rivers and their floodplains, estuaries and the sea, possibly mediating food web subsidies among habitats. To determine the degree of utilisation of food sources from different habitats in a tropical river with a short floodplain inundation duration (~2 months), stable isotope ratios in fishes and their available food were measured from three habitats (inundated floodplain, dry season freshwater, coastal marine) in the lower reaches of the Mitchell River, Queensland (Australia). Floodplain food sources constituted the majority of the diet of large-bodied fishes (barramundi Lates calcarifer, catfish Neoarius graeffei) captured on the floodplain in the wet season and for gonadal tissues of a common herbivorous fish (gizzard shad Nematalosa come), the latter suggesting that critical reproductive phases are fuelled by floodplain production. Floodplain food sources also subsidised barramundi from the recreational fishery in adjacent coastal and estuarine areas, and the broader fish community from a freshwater lagoon. These findings highlight the importance of the floodplain in supporting the production of large fishes in spite of the episodic nature and relatively short duration of inundation compared to large river floodplains of humid tropical regions. They also illustrate the high degree of food web connectivity mediated by mobile fish in this system in the absence of human modification, and point to the potential consequences of water resource development that may reduce or eliminate hydrological connectivity between the river and its floodplain. PMID- 21983713 TI - Biogeographical patterns and co-occurrence of pathogenic infection across island populations of Berthelot's pipit (Anthus berthelotii). AB - Pathogens can exert strong selective forces upon host populations. However, before we can make any predictions about the consequences of pathogen-mediated selection, we first need to determine whether patterns of pathogen distribution are consistent over spatiotemporal scales. We used molecular techniques to screen for a variety of blood pathogens (avian malaria, pox and trypanosomes) over a three-year time period across 13 island populations of the Berthelot's pipit (Anthus berthelotii). This species has only recently dispersed across its range in the North Atlantic, with little subsequent migration, providing an ideal opportunity to examine the causes and effects of pathogenic infection in populations in the early stages of differentiation. We screened 832 individuals, and identified two strains of Plasmodium, four strains of Leucocytozoon, and one pox strain. We found strong differences in pathogen prevalence across populations, ranging from 0 to 65%, and while some fluctuations in prevalence occurred, these differences were largely stable over the time period studied. Smaller, more isolated islands harboured fewer pathogen strains than larger, less isolated islands, indicating that at the population level, colonization and extinction play an important role in determining pathogen distribution. Individual-level analyses confirmed the island effect, and also revealed a positive association between Plasmodium and pox infection, which could have arisen due to dual transmission of the pathogens by the same vectors, or because one pathogen lowers resistance to the other. Our findings, combined with an effect of infection on host body condition, suggest that Berthelot's pipits are subject to different levels of pathogen-mediated selection both across and within populations, and that these selective pressures are consistent over time. PMID- 21983715 TI - The association between cumulative adversity and mental health: considering dose and primary focus of adversity. AB - PURPOSE: The study addressed the dose-response model in the association of cumulative adversity with mental health. METHOD: Data of 1,725 participants aged 50+ were drawn from the Israeli component of the Survey of Health, Ageing, and Retirement in Europe. Measures included an inventory of potentially traumatic events, distress (lifetime depression, depressive symptoms), and well-being (quality of life, optimism/hope). RESULTS: The maximal effect of cumulative trauma emerged in the contrast between 0-2 and 3+ events, where the higher number of events related to higher distress but also to higher well-being. While self oriented adversity revealed no, or negative, association with well-being, other oriented adversity revealed a positive association. CONCLUSIONS: The study suggests an experiential dose of cumulative adversity leading to a co-activation of distress and well-being. The source of this co-activation seems to be other oriented adversity. PMID- 21983714 TI - Reliability and validity of PDQ-39: a quality-of-life measure for patients with PD in China. AB - The syndromes of Parkinson's disease (PD) have impacts on health-related quality of life (HRQL). The 39-item Parkinson's disease Questionnaire (PDQ-39) was the first specific and a consistent instrument for the evaluation of HRQL in PD patients. PURPOSE: To test the reliability and validity of Chinese version PDQ 39. METHODS: Hundred and twenty-six PD without cognitive impairment were enrolled. The Chinese version of SF-36 was used to evaluate the congruent validity of PDQ-39 between related domains. Both PDQ-39 and SF-36 scales were fulfilled by the patients themselves. RESULTS: Five of eight subscales of PDQ-39 met the acceptable standards of reliability (Cronbach's alpha coefficient >0.80), while the other three subscales (cognition, communication, and bodily discomfort) failed to reach the above standards as reported by the others. All the item-to subscale correlations (range: 0.457-0.887) met the minimal acceptable item convergent validity criterion of 0.40 (P < 0.001). Correlation between PDQ-39 subscales and scales of the SF-36 had high negative correlations with a range of 0.759 to -0.124. Four of them had significant negative correlations (P < 0.0001). CONCLUSIONS: The Chinese version of PDQ-39 is a reliable and valid instrument for Chinese PD patients. It is recommended as the most appropriate HRQL tool for PD. PMID- 21983716 TI - [Clinical and mutation analysis of a Chinese family with muscle eye brain disease]. AB - OBJECTIVE: To study the clinical feature of a Chinese family with muscle-eye brain disease (MEB) and the mutation of protein O-linked-mannose beta-1, 2-N acetylglucosaminyltransferase 1 gene (POMGNT1). METHODS: Clinical data of the proband and his family members were collected. Genomic DNA from the patient and his parents was extracted using standard procedures from the peripheral blood leukocytes. Polymerase chain reaction and DNA direct sequencing were employed to analyze all of the exons to determine the mutation, and the relationship between genotype and phenotype was analyzed. RESULTS: The proband was diagnosed as floppy baby, presented with delayed psychomotor development and myopathic face. His serum creatine kinase (CK) level elevated moderately and brain MRI showed cerebral and cerebellar gyrus abnormalities with white matter signal intensity changes, cerebellar cysts and cerebellar and brain stem hypoplasia, consistent with congenital muscular dystrophy with eye brain disorder. Further test with DNA detected a compound heterozygous mutation of c.1896 1 G to C before exon 22 which may induce splicing error, and missense mutation c.1319T to G, p.L440R in exon 16. Both parents had a heterozygous mutation at the mutation sites. CONCLUSION: According to our study, the family is diagnosed as MEB. The proband carried compound heterozygous mutations in the POMGNT1 gene, and his parents are heterozygous carriers, which is consistent with autosomal recessive inheritance. The child is definitely diagnosed as having muscle eye brain disease. PMID- 21983717 TI - [Identification of mutations in PKD1 and PKD2 genes in two Chinese families with autosomal dominant polycystic kidney disease]. AB - OBJECTIVE: To identify the responsible mutation of autosomal dominant polycystic kidney disease (ADPKD) in two Chinese families. METHODS: Total genomic DNA of all available family members and 100 unrelated healthy controls was extracted from peripheral blood leukocytes using a standard phenol-chloroform procedure. All exons with intronic flanking sequences of the PKD1 and PKD2 genes in the probands were amplified by PCR. Mutations were detected directly by DNA sequencing. To evaluate the pathogenicity of the variations, family and control based analyses were performed. RESULTS: Five sequence variants were identified in the two families including PKD1 :c.2469G to A, PKD1:c.5014_5015delAG, PKD1:c.10529 C to T, PKD2:c.568G to A and PKD2:c.2020 1_2020delAG. Among them, PKD1:c.2469G to A and PKD2:c.2020 1_2020 delAG were novel mutations. Furthermore, the frameshift and splicing site mutations detected in the affected individuals were not detected in their unaffected relatives and 100 unrelated normal controls. CONCLUSION: PKD1:c.5014_5015delAG and PKD2:c.2020 1_2020delAG are the responsible mutations of family A and B, respectively, and PKD2:c.2020 1_2020delAG is a de novo mutation. PMID- 21983718 TI - [Mutation analysis of KIF21A gene in a Chinese family with congenital fibrosis of the extraocular muscles type I]. AB - OBJECTIVE: To determine the mutation responsible for the congenital fibrosis of the extraocular muscles type I(CFEOM1) in a Chinese family. METHODS: Direct sequencing of exons 20 and 21 in the KIF21A gene was performed for the proband. The mutation c.2860C to T in exon 21 was examined by allele specific-PCR (AS-PCR) analysis in other family members. Haplotype analysis was performed using four STR markers (D12S1668, D12S2194, D12S331 and D12S1048). RESULTS: A heterozygous mutation c.2860C to T in the KIF21A gene was identified in all three affected members with CFEOM1. Haplotype analysis suggested that the mutation might derive from maternal germline mosaicism. CONCLUSION: This Chinese family with CFEOM1 may be caused by a c.2860C to T mutation in the KIF21A gene. PMID- 21983719 TI - [Clinical characteristics and genetic mutation analysis in a Hui family with Huntington disease]. AB - OBJECTIVE: To perform clinical analysis and gene diagnosis of Huntington disease (HD) in a Hui pedigree from Xinjiang. METHODS: The IT15 gene mutation of the Hui family was analyzed by touchdown PCR, molecular cloning and gene sequencing. RESULTS: The proband carried 46 CAG repeats. Pain in bilateral lower limb was the first symptom, followed by symptoms such as dance like involuntary movements, mood disorders, impaired memory and intelligence. Asymptomatic son of the proband carried 44 CAG repeats. CONCLUSION: This family showed reduced CAG trinucleotide repeats of IT15 gene during maternal transmission. A CAA variation is also detected within the CAG repeat region. PMID- 21983720 TI - [Cellular expression of (R127W)HSPB1 and its co-localization with neurofilament light chain]. AB - OBJECTIVE: To observe the cellular expression of (R127W) HSPB1 and its influence on neurofilament light chain (NFL) self-assembly and co-localization with NFL. METHODS: Eukaryotic expression vectors pEGFPN1-(wt) HSPB1 and pEGFPN1- (R127W) HSPB1 were constructed. Hela cells were transiently transfected with pEGFPN1-(wt) HSPB1 or pEGFPN1- (R127W) HSPB1 and observed under a confocal microscope. Hela cells were also transiently co-transfected with Pcl-NFL and pEGFPN1-(wt)HSPB1, or pCL-NFL and pEGFPN1-(R127W)HSPB1. The self-assembly of NFL was observed and the co-localization study of HSPB1/ (R127W)HSPB1 with NFL was carried out in these two cell models by immunofluorescence technique. RESULTS: The aggregates formed by EGFP-(R127W)HSPB1 predominantly located around the nucleus, and EGFP-(wt)HSPB1 showed diffusion pattern in Hela cells. When co expressed with EGFP-(wt)HSPB1, NFL formed homogeneous structure in cytosol. When co-expressed with EGFP (R127W)HSPB1, however, NFL had amorphous staining pattern predominantly consisting of NFL aggregates, and NFL co-localized with (R127W)HSPB1 in these aggregates. CONCLUSION: The R127W mutant of HSPB1 may have reduced capacity to serve as a chaperone to prevent aggregate formation, and fail to correctly organize the neurofilament network. Dysfunction of the axon cytoskeleton and axon transport may be the primary mechanism of R127W mutation of HSPB1 in the pathogenesis of Charcot-Marie-Tooth disease. PMID- 21983721 TI - [The mitochondrial tRNA(Thr) A15951G mutation may be associated with Leber's hereditary optic neuropathy in two Chinese families]. AB - OBJECTIVE: To explore clinical, genetic and molecular features of two Chinese Han families with Leber's hereditary optic neuropathy (LHON). METHODS: Ophthalmologic examinations revealed variable severity and age-at-onset of visual loss among probands and other matrilineal relatives of both families. The families exhibited extremely low penetrance of visual impairment. The entire mitochondrial genome of two probands was amplified by PCR in 24 overlapping fragments using sets of oligonucleotide primers. RESULTS: Sequence analysis of complete mitochondrial genome in the pedigrees excluded three common LHON associated mutations G11778A, G3460A and T14484C, but revealed the presence of a known homoplasmic tRNA(Thr) A15951G mutation. It also showed distinct sets of mtDNA polymorphisms belonging to Eastern Asian haplogroup D4b1. The A15951G mutation is located at the extremely conserved nucleotide (conventional position 71) of tRNA(Thr). Thus, this mutation may alter the structure and stability of mitochondrial tRNA(Thr), thereby leading to a failure in the tRNA metabolism and mitochondrial dysfunction, causing visual impairment. CONCLUSION: The results suggested that the A15951G mutation might be involved in the pathogenesis of Leber's hereditary optic neuropathy in the two families. PMID- 21983722 TI - [Molecular study of two novel RHD alleles and pedigree analysis]. AB - OBJECTIVE: To study the segregation of two novel RHD alleles in Chinese pedigrees. METHODS: The Rh antigens of the samples were identified by using monoclonal antibodies. The 10 exons of the RHD gene for the 2 probands and their family members were amplified separately and sequenced. The parents of proband 2 were analyzed by sequence specific primer-polymerase chain reaction (SSP-PCR). RESULTS: The two probands were RhD negative and the RHD was D/d type. After alignment with the nucleotide sequence in GenBank, a deletion of nucleotide C at position 78 in exon 1 of proband 1 was detected, and her sister also had the deletion, which was confirmed by sequencing. The sequencing results of proband 2 showed a 10 nucleotide deletion in exon 8 as well as a RHD 520 G to A mutation in exon 4. The results of SSP-PCR and sequencing showed that the proband's mother also carried RHD 520 G to A and RHD 1080 del 10 mutation, which was transmitted to proband 2. The sequences of the novel alleles have been submitted to GenBank (accession No. GQ477180 and GU362076). CONCLUSION: The two novel RHD alleles, RHD 78delC and RHD 520 G to A+1080 del 10, were both pseudo genes and stably transmitted. PMID- 21983723 TI - [The effect of small ubiquitin-like modifier-1 modification on the formation of Lewy body-like inclusions in cytoplasm and apoptosis of HEK293 cell induced by overexpression and mutation of alpha-synuclein]. AB - OBJECTIVE: To investigate the effect of small ubiquitin-like modifier (SUMO-1) modification on the formation of Lewy body like inclusions in cytoplasm and apoptosis of HEK293 cell induced by overexpression and mutation of alpha synuclein. METHODS: cDNA encoding the human alpha-synuclein without the stop codon was cloned into a pGEM T-easy vector. Restriction enzyme mapping and DNA sequencing were performed to analyze the plasmid, which was then subcloned into a pEGFP-N1 vector. The recombinant plasmid alpha-synuclein-pEGFP was transfected into HEK293 cells by lipofectamin method. Inclusions in the cultured cells were identified with HE staining. Apoptosis of the HEK293 cell was measured by Hoechst 33258 staining, MTT and Annexin V-PE flow cytometry. RESULTS: The Lewy-body like inclusions were found in cytoplasm of cultured cells. Hoechst staining showed that the nuclei of cells were enlarged in the wild-type and A53T mutation groups 48 h after transfection, chromatin were accumulated and appeared spot-like. The nucleus stain was equitable in the K96R and K96R-A53T groups. MTT assay showed that the viability of cells transfected with empty plasmid was 96.2%, but it dropped to 53.4% and 56.1% in cells transfected with wild-type alpha-synuclein pEGFP and A53T mutant group, respectively. The viability was 72.3% and 69.8% in cells transfected with K96R and K96R-A53T, respectively (P<0.05). Forty eight hours after transfection, the apoptosis rate was 3.9% in empty plasmid group, 32.2% and 34.1% in cells transfected with wild-type and mutant alpha-synuclein pEGFP, 19.4% and 20.3% in the K96R and K96R-A53T transfected cells. There was significant difference between the two groups (P<0.05). CONCLUSION: SUMO-1 modification did not have influence on the Lewy body-like inclusions formation in cytoplasm of HEK293 cell in vitro, but had a toxic effect which could increase the apoptosis induced by wild type overexpression and mutation of alpha synuclein. PMID- 21983724 TI - [Identification of a novel HLA allele HLA-B*40:96]. AB - OBJECTIVE: To identify a novel human leukocyte antigen (HLA) allele in Chinese and investigate its inheritance in the family. METHODS: Exceptional reaction pattern was detected in HLA-B locus in HLA typing using Luminex DNA polymerase chain reaction with sequence specific oligonucleotide probe hybridization (PCR SSOP) assay. A confirmatory test for the novel HLA allele was performed by DNA sequencing based typing of the proband's family. RESULTS: The DNA sequence was confirmed to be a novel HLA B allele. There were 7 nucleotides which differed from the closest matching HLA B*40:06:01 at positions 302(G to A), 309(G to C), 311(A to C), 313(C to G), 314(T to C), 317(G to T), and 319(G to C) in exon 2, which resulted in 5 amino acid changes at codon 101 (Ser to Asn), 104 (Asn to Thr), 105 (Leu to Ala), 106 (Arg to Leu), and 107 (Gly to Arg), respectively. Family investigation indicated that the novel allele was transmitted from the proband's father. CONCLUSION: A novel HLA B allele was identified and officially named as HLA-B*40:96 (GenBank accession No. FJ374890) by the WHO Nomenclature Committee for Factors of the HLA System. PMID- 21983725 TI - [Study on the expression stability of mutant alpha-1,2 fucosyltransferase gene 293C to T and 658C to T in eukaryotic cells]. AB - OBJECTIVE: To establish the eukaryotic cell expression system for the alpha-1,2 fucosyltransferase gene FUT1 293C to T and 658C to T mutations and explore the mechanism of FUT1 mutations resulting in the reduced expression of H antigen. METHODS: Genomic DNAs were extracted from individuals with para-Bombay phenotype and full coding region of FUT1 was amplified. The amplification fragments were ligated with pcDNA3.1 plasmid to construct the recombinant expression vectors. The recombinant plasmids were transfected into the COS-7 cells using lipofectamine transfection reagent and stable expression screening was performed. FUT1 mRNA expression was determined by real-time quantitative PCR. The activity of enzyme was measured by high performance liquid chromatography. Expressed protein was identified by SDS-PAGE and Western blotting. RESULTS: pcDNA3.1-FUT1 wildtype, pcDNA3.1-FUT1 293C to T and pcDNA3.1-FUT1 658C to T recombinant vectors were constructed, respectively. COS-7 cells with stable expression of FUT1 were obtained through recombinant plasmid transfection and screening with G418. The FUT1 mRNA level of transfected cells with 293C to T and 658C to T recombinant vectors reached 97.10% and 104.74% of the wildtype FUT1 transfected cell. A specific protein band with about 46 000 was confirmed in the transfected cell lysates by SDS-PAGE electrophoresis and Western blotting with 6*His Tag antibody. The wildtype FUT1 transfected cell lysates can catalyze the enzymatic reaction, while the enzyme activity of cell lysates from 293C to T and 658C to T were abolished. CONCLUSION: The results suggested that the 293C to T and 658C to T mutations of FUT1 gene did not affect the RNA and protein expression levels, but the enzyme activity of cells with FUT1 mutations was significantly decreased which resulted in the reduced expressin of H antigen. PMID- 21983726 TI - [Exome sequencing: an efficient strategy for identifying the causative genes of monogenic disorders]. AB - The development of new generation sequencing technologies has brought new opportunities for the study of diseases. Exome sequencing has shown to be an effective, rapid, high performance technique that has already been used in research of inherited diseases such as monogenic disorders. It has already been approved by scientists in the field of monogenic disorder study, and will become widely used. This approach will accelerate discovery of the causative genes of Mendelian disorders. This article reviews some recent applications of exome sequencing in the study of gene-related diseases. PMID- 21983727 TI - [The effect of HSPB8 gene mutation on cell viability in Charcot-Marie-Tooth disease type 2L]. AB - OBJECTIVE: To study the effect of Charcot-Marie-Tooth 2L disease causing gene K141N mutation in heat shock protein B8 gene (HSPB8) on cell viability. METHODS: By using liposome transfection technique, (wt)HSPB8, (K141N)HSPB8 eukaryotic expression vector and green fluorescent protein (GFP) vector were transfected into SHSY-5Y cell, respectively. Twenty-four hours later, the cells were treated with 44 degree centigrade lethal heat shock for 40 minutes. The relative viability of SHSY-5Y cells in each group was tested by using tetrazole blue colorimetric method (methyl thiazolyl tetrazolium, MTT). RESULTS: There were significant differences among the light absorption value of GFP, pEGFP-(wt)HSPB8 and pEGFP-(K141N)HSPB8 transfected groups after heat shock (P<0.05), indicating that the relative viability of cells overexpressed with (wt)HSPB8 and (K141N)HSPB8 was different from that of control cells. The viability of cells overexpressing (wt)HSPB8 was highest, followed by cells overexpressed with (K141N)HSPB8. The viability of cells tranfected with GFP only was the lowest. CONCLUSION: HSPB8 may play an important role in the protection of cells under lethal heat shock treatment, and the K141N mutation can impair the protective effect. PMID- 21983728 TI - [Association of matrix metalloproteinase 9 polymorphisms with adolescent idiopathic scoliosis in Chinese Han female]. AB - OBJECTIVE: To determine whether the matrix metalloproteinase 9 gene (MMP9) polymorphism is associated with the onset or progression of adolescent idiopathic scoliosis (AIS) in Chinese Han female. METHODS: Three single nucleotide polymorphisms (SNPs) (rs17576, rs2250889, rs1805088) were genotyped through TaqMan-based real-time PCR assay in 190 AIS patients and 190 controls, all of whom were females from Chinese Han population with matched age. Analyses performed included Hardy Weinberg equilibrium test, Pearson chi-square test, Logistic regression analysis, linkage disequilibrium analysis and haplotype analysis. The mean maximum Cobb angles with different genotypes in case-only dataset were also compared. RESULTS: All 3 SNPs have reached Hardy-Weinberg equilibrium in the controls. Genotype and allele frequencies of all SNPs were found similar between cases and controls by Pearson chi-square test and Logistic regression. Genotype-phenotype analysis showed that patients with CC genotype in rs2250889 featured larger maximum Cobb angles. CONCLUSION: MMP9 may not be a predisposition gene of AIS in Han female. However, homozygous mutation in rs2250889 can render scoliosis more severe, implying that MMP9 defect may result in deterioration of AIS. PMID- 21983729 TI - [Prenatal diagnosis of mucopolysaccharidosis type II]. AB - OBJECTIVE: To establish a method of iduronate-2-sulfatase (IDS) activity assay and mutation analysis of IDS gene for the prenatal diagnosis of mucopolysaccharidosis type II (MPSII). METHODS: Prenatal diagnosis of two cases was performed using cultured fetal amniotic fluid cells. Enzyme activity of IDS in cultured fetal amniotic fluid cells extracted from the two pregnant women at high risk of MPS II was measured. Meanwhile, genomic DNA was extracted for fetal gender testing and mutation analysis of the IDS gene. RESULTS: Enzyme activity assay showed that IDS activity in amniotic fluid cells was significantly decreased. IDS gene sequencing showed that the male fetus was hemizygous mutant, and the female fetus was carrier of heterozygous mutation. Therefore the male fetus was an MPS II patient and the female fetus was a mutation carrier. CONCLUSION: Determination of IDS activity in fetal amniotic fluid cells together with IDS gene mutation analysis is a rapid, sensitive and accurate method of prenatal diagnosis of MPS II. Using this method, prenatal diagnosis for pregnant women at high risk of MPSII can be achieved. PMID- 21983730 TI - [A family-based association study of FXYD6 gene polymorphisms and schizophrenia]. AB - OBJECTIVE: To study the association between the single nucleotide polymorphisms (SNPs) in FXYD6 gene and schizophrenia in a family-trios population. METHODS: Six SNPs (rs10790212, rs11544201, rs555577, rs1815774, rs4938446 and rs497768) in the FXYD6 gene were genotyped by allele-specific PCR method in 101 nuclear families, and transmission disequilibrium test (TDT) was performed. RESULTS: SNPs rs10790212 and rs11544201 showed significant association with schizophrenia (P<0.05). Furthermore, significant association of schizophrenia with the haplotype rs10790212-rs11544201 was found (P<0.05). CONCLUSION: FXYD6 gene might play an important role in schizophrenia susceptibility and functional analysis of FXYD6 are needed. PMID- 21983731 TI - [Application of multiplex ligation-dependent probe amplification for rapid detection of aneuploidies in prenatal diagnosis]. AB - OBJECTIVE: To determine the applicability of multiplex ligation-dependent probe amplification (MLPA) for rapid detection of aneuploidies in prenatal diagnosis. METHODS: A total of 561 prenatal samples were analyzed in parallel by MLPA and traditional karyotyping. Another 20 clinical samples with known common chromosome abnormalities were also determined by MLPA to evaluate the accuracy and reliability of MLPA. The results obtained from MLPA were compared with that from traditional karyotyping. RESULTS: The results were available within 48 h. A total of 38 aneuploidies were identified by MLPA, including 20 cases of trisomy 21, 10 cases of trisomy 18, 1 case of trisomy 13, 4 cases of Turner syndrome, 1 case of Klinefelter syndrome, 1 case of 47, XYY trisomy and 1 case of 48,XYY, +18. MLPA was able to detect all the expected aneuploidies with 100% accuracy. The results obtained from MLPA agreed with traditional karyotyping. Among 561 prenatal samples, the results of 550 samples were concordant with those of karyotyping, and the coincidence rate of MLPA was 98.04%. CONCLUSION: MLPA is a rapid, simple and reliable method for detection of the most common chromosome aneuploidies in prenatal diagnosis. MLPA is a valuable tool in prenatal clinical practice. PMID- 21983732 TI - [Identification of an ABx09 phenotype of ABO subtype]. AB - OBJECTIVE: To analyze the molecular basis for an individual with ABx09 phenotype of ABO subtype. METHODS: The ABO group antigens on red blood cells of the proband were identified by monoclonal antibodies, and the ABO antibody in serum was detected by standard A, B, O cells. The exons 1 to 7 of ABO gene were amplified by polymerase chain reaction (PCR) respectively and the PCR products were sequenced directly. The amplified products for exons 5 to 7 were also cloned by TOPO TA cloning sequencing kit to split the two alleles apart, selected colonies were sequenced bidirectionally for exons 5 to 7 of the ABO gene. The samples of the proband's parents were collected, then serological test of the blood group and sequence analysis for exons 6 and 7 of ABO gene were preformed. RESULTS: Both A and B antigens were detected on red blood cells of the proband and there was anti-B antibody in the serum. There was no G deletion at position 261, while 297AG in exon 6, 467CT, 526CG, 657CT, 703GA, 796CA, 803GC, 889GA and 930GA heterozygote in exon 7 were detected by direct DNA sequencing, which can be assigned for A102Bx09 genotype. After cloning and sequencing, two alleles A102 and Bx09 were obtained. The sequence of Bx09 had one nucleotide changes (G to A) at position 889 compared with that of B101, which resulted in an amino acid change of Glu to Lys at 297 position. The Bx09 in the proband was inherited from her mother by family investigation. CONCLUSION: G to A at nt889 of alpha-1,3 galactosyltransferasegene can result in Bx09 phenotype, with the presence of anti B antibody in serum. PMID- 21983733 TI - [The serological and genetic identification of a CisAB blood sample]. AB - OBJECTIVE: To verify the DNA sequence of a sample serologically identified as CisAB. METHODS: Forward and reverse group methods were used to determine the blood serological type of that the sample, and PCR-sequence specific primer (PCR SSP) method was used for genotyping the sample. RESULTS: Serologically, the forward group test showed that the sample was AB, while the reverse group test showed that the sample had the anti-B and anti-H + + +. The auto antibodies were negative. PCR-SSP assay showed the sample was CisAB01. ABO genetic locus sequencing showed c.261delG in exon 6, c.297 was homozygous AA. Mutations c.467C to T and c.803G to C were found in exon 7. A novel heterozygous mutation, c.724G to T, was detected. CONCLUSION: The serological phenotype of the specimen was CisAB. The genotype was ABO *CisAB01 and ABO *O01. A novel mutation c.724G to T in exon 7 was identified (GenBank accession no. JF304777). PMID- 21983734 TI - [Association of the IL-6 gene 634C/G polymorphism with susceptibility to endometriosis]. AB - OBJECTIVE: To investigate the association of interleukin 6 gene (IL-6) promoter region 634C/G (rs1800796) single nucleotide polymorphism (SNP) with the genetic susceptibility to endometriosis (Ems) in south Han Chinese women. METHODS: A case control study was performed in 432 Ems patients and 499 control women to evaluate the SNP of IL-6 634C/G by using a fluorescent quantitative PCR-based high resolution melting (HRM) method. RESULTS: There were statistical significances in the IL-6 634C/G alleles, whether or not to carry allele G and genotype distributions between Ems patients and control women (P=0.032, 0.014 and 0.045, respectively). Allele C enhanced the risk of Ems 1.057 times while allele G reduced the risk of Ems 0.835 time. Carrying allele G reduced the risk of Ems 0.822 time, whereas not carrying allele G enhanced the risk of Ems 1.143 times. Compared with genotype CC, the risk of Ems with genotype CG reduced 0.704 time (95% CI: 0.533-0.931). There was no significant difference in whether or not carrying allele G distribution between Ems patients and control women (P=0.729). CONCLUSION: The present study demonstrated significant association between the SNP of IL-6 634C/G and genetic susceptibility to Ems in south Han Chinese women. PMID- 21983735 TI - [Relationship between follicle stimulating hormone and AZF microdeletion on Y chromosome in patients with azoospermia or severe oligozoospermia]. AB - OBJECTIVE: To investigate the relationship between follicle stimulating hormone (FSH) and AZF microdeletion on Y chromosome. METHODS: Fifteen loci of 4 regions of the AZF gene were investigated by multiplex PCR in 100 patients with azoospermia or severe oligozoospermia. The reproductive hormone FSH was detected by access 2 immunoassay system from BECKMAN COULTER. Epidata was set up and analyzed for means. F test of anova was performed. RESULTS: The rate of microdeletion was 13% (13 out of 100 patients). The deletion was on AZFa in 1 patient, AZFb+c+d in 4 patients, AZFc+d in 7 patients, AZFd in 1 patient, respectively. The level of FSH (40.8+/-11.3 U/L) in the AZFb+c+d deletion group was significantly higher than that in the group without Y chromosome deletion (16.7+/-14.3 U/L) and the other types of deletion (11.8+/-6.7 U/L) (P<0.01). CONCLUSION: The common microdeletion regions were AZFc and AZFd on Y chromosome in azoospermia or severe oligozoospermia. The microdeletion of AZFb+c+d was one of the important causes of the high level of FSH. PMID- 21983736 TI - [Association of leptin level and leptin receptor gene polymorphisms with susceptibility to severe pre-eclampsia]. AB - OBJECTIVE: To evaluate the association of serum leptin concentrations and polymorphisms of G1019A and A223G of leptin receptor gene (LEPR) with severe pre eclampsia. MEHTODS: A case-control study was carried out in 207 patients with severe pre-eclampsia (SPE group) and 252 healthy pregnant women (control group) during the third trimester of pregnancy. The serum leptin was determined by enzyme-linked immunosorbent assay. The polymorphisms of LEPR gene G1019A and A223G were detected by polymerase chain reaction restriction-fragment length polymorphism (PCR-RFLP) analysis. Miettinen's test was used to estimate the odds ratios (OR) and 95% confidence intervals (CI). RESULTS: (1) In severe pre eclampsia group, serum leptin levels and rate of premature infant birth were significantly higher than that in normal pregnant women, and birth weight was lower than that in controls (P<0.01). (2) The frequencies of GA genotype and G allele for LEPR gene G1019A in SPE group (33.8% and 20.3%) were markedly higher than that in controls (19.8% and 15.1%) (P<0.01), and the carriers of GA genotype and G allele were more frequent in SPE group than in control group, resulting in an OR 2.04 (95%CI: 0.77-5.42) and 1.43 (95%CI: 1.02-2.01) to develop severe pre eclampsia, compared with carriers of AA genotype and A allele. (3) AG genotype and A allele frequencies of LEPR gene A223G in SPE group (19.3% and 12.6%) were significantly lower than that in controls (34.5% and 19.2%) (P<0.01), resulting in an OR of 0.46 (95%CI: 0.30-0.71) and 0.60 (95%CI: 0.42-0.87) to develop severe pre-eclampsia, compared with subjects with GG genotype and G allele. (4) The "1019AA+223AG" genotype frequency was significantly lower in SPE group (6.8%) than in controls (24.6%) (P<0.01), resulting in an OR of 0.22 (95%CI: 0.12-0.39) to develop severe pr-eclampsia, while the "1019AA+223AG" was significantly higher in SPE group (22.2%) than in controls (11.9%) (P<0.05), resulting in an OR of 2.10 (95%CI: 0.78-3.45) to develop severe pre-eclampsia. (5) No significant differences were found in SBP, DBP, BMI and serum leptin levels in subjects with different genotypes in the two groups (P>0.05). CONCLUSION: Elevated serum leptin level and LEPR gene G1019A and A223G polymorphisms might play a role in severe pre-eclampsia, while the level of serum leptin was not associated with genotypes of LEPR gene G1019A and A223G polymorphisms. The genotypes GA and "1019AA+223AG"of G1019A may be genetic susceptibility factors to severe pre eclampsia. PMID- 21983737 TI - [Combined use of molecular cytogenetic techniques to detect a small chromosomal translocation]. AB - OBJECTIVE: Comprehensive use of molecular cytogenetic techniques for the detection of 1 case of small chromosome translocation. METHODS: Following conventional chromosome preparation, G-banding karyotype analysis, spectral karyotyping (SKY), whole chromosome painting, two-color fluorescence in situ hybridization (FISH) and subtelomeric probe FISH were performed. RESULTS: G banded karyotype was 46, XX, ?(22q11.3), SKY karyotype analysis was 46, XX, der (4)t(4;6) and found no abnormalities on chromosome 22, staining signal was not found with any abnormalities on chromosome 6. Two-color FISH indicated a chromosomal translocation segment of 22q13.3 to one end of the short arm of chromosome 4. Subtelomeric FISH probe showed the end of the long arm of chromosome 22 and the end of the short arm of chromosome 4 reciprocal translocation. High resolution G-banding and FISH result indicated 46, XX, t(4;22)(p15.3;q13.2). CONCLUSION: The testing of small chromosomal translocation should be combined with clinical information and integrated use of molecular cytogenetic techniques to improve the accuracy of diagnosis of chromosomal diseases. PMID- 21983738 TI - [Association of filaggrin gene polymorphism with atopic dermatitis in southern Chinese Han population]. AB - OBJECTIVE: To investigate the association of filaggrin gene (FLG) polymorphism with atopic dermatitis (AD) in southern Chinese Han population. METHODS: The frequencies of the 13 known FLG gene single nucleotide polymorphism(SNPs), including 3321delA, 441delA, 1249insG, E1795X, S3296X, R501X, 2282del4, R2447X, S2889X, 7945delA, 3702delG, Q2417X, R4307X, were detected in a cohort of 50 AD patients and 100 control individuals using polymerase chain reaction (PCR) and DNA sequencing. RESULTS: FLG 3321delA and 441delA were detected in 14 (28%) and 6 (12%) AD patients, respectively. The other 11 SNPs were not detected in the patients. None of the 13 SNPs was detected in the controls. CONCLUSION: The results suggested that the FLG gene might be associated with atopic dermatitis susceptibility in southern Chinese Han population. PMID- 21983739 TI - [Analysis of fetal chromosomal karyotype and etiology in 252 cases of early spontaneous abortion]. AB - OBJECTIVE: To investigate the relationship between fetal chromosomal karyotype and early spontaneous abortion, and the effect of the environmental factors on spontaneous abortion. METHODS: Choronic villi from 252 cases of missed abortion were sampled as patient group and 50 normal pregnancies as control group. Chorionic villi were cultured and karyotype analysis was performed by G-banding. Clinical information was collected. RESULTS: The rate of chorion chromosome abnormality in the patient group was 58.09%, significantly higher than that in the control group (4.17%) (P<0.01). Among the 140 cases of karyotype abnormalities, 81 were trisomy, 29 were monosomy X and 17 were polyploidy, accounting for 57.86%, 20.71% and 12.14% of total abnormalities, respectively. Long time and low dose radiation exposure of the pregnant female seemed to be related with spontaneous abortion(P<0.01). CONCLUSION: Chorion chromosome abnormality is a major reason of early spontaneous abortion and karyotype analysis of chorionic villus is of clinical importance. For pregnant women, long term exposure to computers and television seems a risk factor for missed abortion. PMID- 21983740 TI - [Epidemiological study of thalasaemia among children in Xishuangbanna, Dehong and Nujiang of Yunnan province]. AB - OBJECTIVE: To investigate the carrier rate of thalasaemia among the children of 10 minority ethnic groups in 3 border states (Xishuangbanna, Dehong and Nujiang) of Yunnan Province. METHODS: A total of 6562 samples of children under 10 years old were analyzed by blood cell automatic analysis and hemoglobin electrophoresis. RESULTS: The overall carrier frequency of thalasaemia was highest (46.2%) in Dehong, and lowest (30.6%) in Nujiang. The carrier frequency of beta-thalasaemia was the highest (40.6%) in Achang, and lowest (2.5%) in Dulong. The carrier frequency of alpha-thalasaemia was the highest (22.1%) in Dai from Xishuangbanna, followed by Dulong (19.1%). CONCLUSION: Thalasaemia carrier rates were high among the children of 10 minority ethnic groups in Yunnan. There were regional differences in their incidences. The results provide a valuable basis for thalasaemia prevention in Yunnan minorities in the three border states. PMID- 21983741 TI - [Association between diversity of hypoxia at different altitude and the polymorphism of EPAS1 gene]. AB - OBJECTIVE: To study the selection effect of endothelial PAS domain protein 1 (EPAS1) gene induced by high altitude hypoxia environment. METHODS: Fourteen single nucleotide polymorphism sites (SNPs) of the EPAS1 gene were genotyped using PCR-restriction fragment length polymorphism (PCR-RFLP) in three Tibetan groups (58 samples from Tibetan living in an altitude of about 3700 meters above sea level, 47 from Qinghai province, about 3100 meters above sea level, 43 from Yunnan province, about 2500 meters above sea level), and Han of Shandong (47 samples, about 50 meters above sea level). RESULTS: There were significant differences of most SNP allelic, genotypic and haplotypic frequencies when comparing Han of Shandong, Tibetan of Yunnan with Tibetan of Tibetan and Qinghai. But no difference between Han of Shandong and Tibetan of Yunnan was found. CONCLUSION: The EPAS1 gene might be under hypoxic selection induced by high altitude. PMID- 21983742 TI - Alternative startle motor patterns and behaviors in the larval zebrafish (Danio rerio). AB - In fishes, the C-start behavior, initiated with a C-shaped body bend, is a taxonomically common and widely studied escape response. Its simple neural circuit has made this behavior a model for examining neural control of movement. The S-start, initiated with an S-shaped body bend, is a physiologically distinct escape that occurs in esocid fishes. Here we examine whether zebrafish larvae perform S-starts in order to better understand startle diversity and to attempt to identify the S-start in a system that is tractable for neurobiological studies. We found that larval zebrafish startles varied in the extent of their caudal bending, resulting in C, S and intermediate-shaped responses. We recorded two distinct motor patterns: nearly simultaneous initial activity along one side of the body, characteristic of C-starts, and nearly simultaneous activity rostrally on one side and caudally on the other, characteristic of S-starts. Head stimulation generally elicited C-starts while tail stimulation elicited C- and S starts. These results demonstrate that the S-start is more common than previously documented and occurs in early developmental stages. We suggest that the S-start may be a fundamental escape behavior in fishes and may provide a comparative model to the C-start for understanding simple neural circuits. PMID- 21983743 TI - Laser-induced withdrawal test for electrophysiological recordings of nociception. AB - CO(2) lasers are often used in pain research. However, the stimulation parameters of the CO(2) lasers, such as beam diameter, laser power, etc., used for these animal nociceptive studies vary across laboratories. The differences of the parameters usually make novices who want to reproduce the laser-evoked responses confused to follow. In this study, we quantitatively measured the laser withdrawal reflex of the rat to ascertain the individual laser-withdrawal threshold and then found the thresholds were diverse among the rats we adopted. Furthermore, the optimal stimulation distance, the most conveniently modified stimulation parameter of CO(2) laser stimuli, was also determined. We suggest that laser-withdrawal tests should be applied before the electrophysiological recordings in order to verify the efficiency of the induced nociception and substantiate the operational parameters of the CO(2) laser device. PMID- 21983744 TI - Gender-dependent metabolic remodeling during heart preservation in cardioplegic celsior and histidine buffer solution. AB - Understanding heart metabolism during preservation is crucial to develop new effective cardioplegic solutions. We aim to investigate metabolic alterations during heart preservation in the clinically used Celsior (Cs) and histidine buffer solution (HBS). We also focused in gender-specific metabolic adaptations during ischemia. We followed energy metabolism in hearts from men and women preserved during 6 hours in Cs and HBS. Hearts were subjected to cold ischemia (4 degrees C) in Cs or HBS, and aliquots of the cardioplegic solution were collected throughout preservation for nuclear magnetic resonance analysis. HBS-preserved hearts from men consumed glucose mostly between 240 and 360 minutes, whereas HBS preserved hearts from women consumed glucose throughout the 6 hours of ischemia. Lactate production rates followed approximately the glucose consumption rates in HBS-preserved hearts. The lactate to alanine ratio, an indicator of the redox state, was increased in HBS-preserved hearts when compared with Cs-preserved hearts. Hearts from men presented a higher redox state than those from women preserved in Cs after 300 minutes. Both Cs and HBS were capable of preventing acidification in hearts from women but not in hearts from men, which decreased the extracellular pH. HBS-preserved hearts from men and women produced 0.1 +/- 0.01 and 0.15 +/- 0.03 MUmol.min(-1).gdw(-1) of lactate, respectively. Those rates were significantly higher than in Cs-preserved hearts. Thus, Cs was more effective in preventing lactate production. We conclude that glycolysis and lactate production are stimulated in HBS-preserved hearts. HBS shows better overall results particularly in hearts from women, which presented less extracellular acidification and were more effective in recycling the metabolic subproducts. PMID- 21983745 TI - Alteration of purinergic neurotransmission in isolated atria of streptozotocin induced diabetic rats. AB - Cardiac dysfunctions are described in diabetes. However, the role of purinergic neurotransmission in diabetes-related cardiovascular diseases is unknown. The purpose of this study was to evaluate the purinergic neurotransmission in isolated atria from streptozotocin-induced diabetic rats. The animals were grouped as control and diabetic with 30 days (D30) and 60 days (D60) after streptozotocin-induced diabetes. The isolated left and right atria were used in functional experiments. The effects of adenosine triphosphate, uridine diphosphate, and adenosine were evaluated on atrial inotropism and chronotropism. The antagonists 8-cyclopentyl-1,3-dipropylxanthine and pyridoxal-phosphate-6 azophenyl-2',4'-disulfonate were also used, as blockers of P1 and P2 receptors, respectively. A negative inotropic effect followed by a positive inotropic effect was induced by adenosine triphosphate in isolated atria. This negative inotropic effect was decreased by 25% in left atria of D30. Additionally, the apparent affinity for adenosine was diminished in left atria of D30, suggesting changes in P1 receptor function. No changes were found in the right atria of D30 stimulated by adenosine. The left atria and right atria stimulated by uridine diphosphate showed an increased inotropic effect of 92% and 17%, respectively. No changes were observed in left and right atria of D30 stimulated by uridine diphosphate. Our data showed the involvement of purinergic neurotransmission in diabetes related cardiovascular changes. PMID- 21983746 TI - Efficacy of colesevelam on lowering glycemia and lipids. AB - A few trials have investigated the efficacy of colesevelam in the reduction of glycemic and lipid outcomes. These meta-analysis pooled data from 8 such trials and found that colesevelam is associated with significant reductions in plasma fasting glucose, hemoglobin A1c, and low-density lipoprotein. Insignificant reductions in high-density lipoprotein and total cholesterol were also noted along with significant increase in triglycerides. This analysis concludes that colesevelam may be of particular benefit in managing type 2 diabetic patients with hyperlipidemia in whom low-density lipoprotein levels are of particular concern. Caution should be taken in patients who have hypertriglyceridemia or low high-density lipoprotein levels before starting therapy. PMID- 21983747 TI - Antirestenotic mechanisms of everolimus on human coronary artery smooth muscle cells: inhibition of human coronary artery smooth muscle cell proliferation, but not migration. AB - Everolimus, a pharmaceutical component of drug-eluting stents, inhibits coronary vessel restenosis, but the antirestenotic mechanisms of action remain unclear. Here, we describe the effects of everolimus on key contributors to vessel restenosis, smooth muscle cell proliferation, and migration. In a dose-dependent fashion, everolimus reduced human coronary artery smooth muscle cell (HCASMC) proliferation without toxicity in a bimodal fashion, with accentuated potency occurring at 10 MUM. Everolimus arrested the majority of HCASMCs in G1-phase, whereas it reduced the fraction of cells in S-phase at doses that inhibited DNA synthesis (bromodeoxyuridine incorporation). Consistent with this, Western blotting demonstrated that everolimus reduced activation and expression of G1 phase cell cycle progression factors, including p70S6K and cyclin D, respectively, decreased levels of proliferating cell nuclear antigen, and attenuated growth factor/serum-induced phosphorylation of the cell cycle phase transition intermediate, retinoblastoma protein. Everolimus did not, however, affect HCASMC migration. These observations suggest that everolimus acts as an antiproliferative, but not antimigratory, compound to account for at least some of the clinical efficacy exhibited by this drug as an antirestenotic agent. Moreover, everolimus-induced inhibition of the mammalian target of rapamycin complex 1 and regulation of cyclin-mediated cell cycle progression actions likely account for the antiproliferative effects of this compound on HCASMCs. PMID- 21983748 TI - Neuroprotective and anti-oxidative effects of the hemodialysate actovegin on primary rat neurons in vitro. AB - The recently described therapeutic benefits of the hemodialysate actovegin on neuropathic symptoms in diabetic patients with symptomatic polyneuropathy suggest a neuroprotective activity of the drug. To elucidate the possible cellular mechanism of the pharmacological effects of actovegin, we investigated its effects on cultured primary rat neurons in vitro. Primary neurons were cultured for up to 10 days in the presence of increasing doses of actovegin (0.3-1,000 mg/l). Total cell number, dendrite length and the number of excitatory synapses, i.e., the amount of the synaptic V-Glut1 protein, were measured by immunocytochemistry followed by fluorescence microscopy. The apoptotic level in neurons after induction of apoptosis by amyloid peptide Abeta(25-35) was assessed by the level of activated caspase-3. In addition, the capability of the neurons to diminish oxidative stress was assessed by measuring the cellular level of reactive oxygen species ROS in the presence of actovegin. Actovegin treatment yielded an increased maintenance of neuronal cells and total number of synapses and could lower the level of activated caspase-3 in a dose-dependent manner. Dendrite lengths were not significantly affected. In addition, actovegin reduced the cellular level of ROS in cultured neurons. The cellular effects observed suggest neuroprotective and anti-oxidative effects of the drug Actovegin((r)), which could at least partially explain its therapeutic benefits. PMID- 21983751 TI - Magneto-structural correlations in dinuclear Mn(III) compounds with formula [{Mn(L)(NN)}(MU-O)(MU-2-RC6H4COO)2{Mn(L')(NN)}]n+. AB - Three dinuclear Mn(III) compounds with oxo and carboxylato bridges have been synthesized and characterized by X-ray diffraction: [{Mn(L)(NN)}(MU-2 ClC(6)H(4)COO)(2)(MU-O){Mn(L')(NN)}](n+) with NN = 2,2'-bipyridine (1 and 2) or 1,10-phenanthroline (3). The counteranion is either NO(3)(-) (1 and 3) or ClO(4)( ) (2) and the monodentate positions (L, L') could be occupied by molecules of water or the counteranion. For compound 1, L = H(2)O and L' = NO(3)(-); compound 2 shows two different dinuclear units and L and L' could be H(2)O or ClO(4)(-), and for compound 3 both monodentate positions are occupied by nitrate anions. The magnetic properties of the three compounds have been analyzed using the Hamiltonian H = -JS(1).S(2). Compound 1 exhibits a dominant ferromagnetic behavior, with J = 3.0 cm(-1), |D(Mn)| = 1.79 cm(-1), |E(Mn)| = 0.60 cm(-1) with intermolecular interactions zJ' = -0.18 cm(-1). Due to the anisotropy of the Mn(III) ions, the ground state S = 4 shows ZFS with |D(4)| = 0.58 cm(-1). Compounds 2 and 3 show antiferromagnetic couplings, with J = -10.9 and -0.3 cm( 1), respectively. The magnetic interaction in this kind of compound depends on several structural factors. In the present work, the distortion around manganese ions, the torsion angle between the phenyl ring and the carboxylate group and the relative disposition of the coordination octahedra have been analyzed. PMID- 21983750 TI - The effect of high-intensity intermittent swimming on post-exercise glycogen supercompensation in rat skeletal muscle. AB - A single bout of prolonged endurance exercise stimulates glucose transport in skeletal muscles, leading to post-exercise muscle glycogen supercompensation if sufficient carbohydrate is provided after the cessation of exercise. Although we recently found that short-term sprint interval exercise also stimulates muscle glucose transport, the effect of this type of exercise on glycogen supercompensation is uncertain. Therefore, we compared the extent of muscle glycogen accumulation in response to carbohydrate feeding following sprint interval exercise with that following endurance exercise. In this study, 16-h fasted rats underwent a bout of high-intensity intermittent swimming (HIS) as a model of sprint interval exercise or low-intensity prolonged swimming (LIS) as a model of endurance exercise. During HIS, the rats swam for eight 20-s sessions while burdened with a weight equal to 18% of their body weight. The LIS rats swam with no load for 3 h. The exercised rats were then refed for 4, 8, 12, or 16 h. Glycogen levels were almost depleted in the epitrochlearis muscles of HIS- or LIS exercised rats immediately after the cessation of exercise. A rapid increase in muscle glycogen levels occurred during 4 h of refeeding, and glycogen levels had peaked at the end of 8 h of refeeding in each group of exercised refed rats. The peak glycogen levels during refeeding were not different between HIS- and LIS exercised refed rats. Furthermore, although a large accumulation of muscle glycogen in response to carbohydrate refeeding is known to be associated with decreased insulin responsiveness of glucose transport, and despite the fact that muscle glycogen supercompensation was observed in the muscles of our exercised rats at the end of 4 h of refeeding, insulin responsiveness was not decreased in the muscles of either HIS- or LIS-exercised refed rats compared with non exercised fasted control rats at this time point. These results suggest that sprint interval exercise enhances muscle glycogen supercompensation in response to carbohydrate refeeding as well as prolonged endurance exercise does. Furthermore, in this study, both HIS and LIS exercise prevented insulin resistance of glucose transport in glycogen supercompensated muscle during the early phase of carbohydrate refeeding. This probably led to the enhanced muscle glycogen supercompensation after exercise. PMID- 21983752 TI - Structural bioinformatics of Neisseria meningitidis LD-carboxypeptidase: implications for substrate binding and specificity. AB - Neisseria meningitidis, a gram negative bacterium, is the leading cause of bacterial meningitis and severe sepsis. Neisseria meningitidis genome contains 2,160 predicted coding regions including 1,000 hypothetical genes. Re-annotation of N. meningitidis hypothetical proteins identified nine putative peptidases. Among them, the NMB1620 protein was annotated as LD-carboxypeptidase involved in peptidoglycan recycling. Structural bioinformatics studies of NMB1620 protein using homology modeling and ligand docking were carried out. Structural comparison of substrate binding site of LD-carboxypeptidase was performed based on binding of tetrapeptide substrate 'L-alanyl-D-glutamyl-meso-diaminopimelyl-D alanine'. Inspection of different subsite-forming residues showed changeability in the S1 subsite across different bacterial species. This variability was predicted to provide a structural basis to S1-subsite for accommodating different amino acid residues at P1 position of the tetrapeptide substrate 'L-alanyl-D glutamyl-meso-diaminopimelyl-D-alanine'. PMID- 21983749 TI - Shiga toxin pathogenesis: kidney complications and renal failure. AB - The kidneys are the major organs affected in diarrhea-associated hemolytic uremic syndrome (D(+)HUS). The pathophysiology of renal disease in D(+)HUS is largely the result of the interaction between bacterial virulence factors such as Shiga toxin and lipopolysaccharide and host cells in the kidney and in the blood circulation. This chapter describes in detail the current knowledge of how these bacterial toxins may lead to kidney disease and renal failure. The toxin receptors expressed by specific blood and resident renal cell types are also discussed as are the actions of the toxins on these cells. PMID- 21983753 TI - Sensitivity assessment of freshwater macroinvertebrates to pesticides using biological traits. AB - Assessing the sensitivity of different species to chemicals is one of the key points in predicting the effects of toxic compounds in the environment. Trait based predicting methods have proved to be extremely efficient for assessing the sensitivity of macroinvertebrates toward compounds with non specific toxicity (narcotics). Nevertheless, predicting the sensitivity of organisms toward compounds with specific toxicity is much more complex, since it depends on the mode of action of the chemical. The aim of this work was to predict the sensitivity of several freshwater macroinvertebrates toward three classes of plant protection products: organophosphates, carbamates and pyrethroids. Two databases were built: one with sensitivity data (retrieved, evaluated and selected from the U.S. Environmental Protection Agency ECOTOX database) and the other with biological traits. Aside from the "traditional" traits usually considered in ecological analysis (i.e. body size, respiration technique, feeding habits, etc.), multivariate analysis was used to relate the sensitivity of organisms to some other characteristics which may be involved in the process of intoxication. Results confirmed that, besides traditional biological traits, related to uptake capability (e.g. body size and body shape) some traits more related to particular metabolic characteristics or patterns have a good predictive capacity on the sensitivity to these kinds of toxic substances. For example, behavioral complexity, assumed as an indicator of nervous system complexity, proved to be an important predictor of sensitivity towards these compounds. These results confirm the need for more complex traits to predict effects of highly specific substances. One key point for achieving a complete mechanistic understanding of the process is the choice of traits, whose role in the discrimination of sensitivity should be clearly interpretable, and not only statistically significant. PMID- 21983754 TI - Electroconvulsive therapy in Norway: rates of use, clinical characteristics, diagnoses, and attitude. AB - OBJECTIVES: The aim of the study was to describe the rate of use and demographic distribution of electroconvulsive therapy (ECT) in Norway in 2004, as well as the attitudes among Norwegian psychiatrists about ECT. METHODS: A 42-item questionnaire on the practice of ECT was sent to 125 Norwegian psychiatric hospitals, district psychiatric centers, and child and adolescent psychiatric units in 2004. RESULTS: A total of 67 (54%) psychiatric units responded, including 26 (67%) of 39 psychiatric hospitals, 32 (46%) of 69 district psychiatric centers, and 9 (53%) of 17 child and adolescent units. There were 672 patients who received ECT during 2004, which gives a yearly incidence of 2.4 of 10,000 inhabitants. A total of 5.3% of all inpatients received ECT.The rate of ECT use varied from 1.83 to 3.44 per 10,000 inhabitants per year between the different health regions.Of the 672 patients, 394 reported their sex (59%), of which 135 were men and 259 were women (male-female ratio, 1:2). The most common diagnosis treated with ECT was depression, followed by bipolar disorder and schizoaffective disorder.The responders expressed generally positive attitudes toward ECT. Almost all considered ECT important, that hospitals should offer ECT, and that there are solid indications for such treatment. Most of the responders expressed concern about the underuse of ECT. CONCLUSIONS: Electroconvulsive therapy is widely available in Norway but its use is unevenly distributed between health regions. The attitudes toward ECT are generally positive among psychiatrists. PMID- 21983755 TI - Access to electroconvulsive therapy services in Canada. AB - OBJECTIVES: We sought to determine factors governing access to electroconvulsive therapy (ECT) in Canada. METHODS: We contacted all 1273 registered health care institutions in Canada and invited the 175 centers identified as providing ECT to complete a comprehensive questionnaire. To determine geographic access to ECT, we used a geographic information system, population density data, and road network data. Responses to 5 questions from the questionnaire were used to identify local barriers to access. RESULTS: Approximately 84% of the population in the 10 Canadian provinces live within a 1-hour drive of an ECT center, but 5% live more than 5 hours' drive away. There was significant province-to-province variation, with all of the citizens of Prince Edward Island living within 2 hours of an ECT center but 12.5% of those in Newfoundland and Labrador living more than 5 hours' distance away. There are no ECT services at all in the 3 territories, which contain 3% of the Canadian population. Nongeographic barriers to access included inadequate human resources, particularly, a lack of anesthesiologists, in 59% of the centers; logistical impedances (52%); space limitations (45%); strictures on the hiring of adequate staff (29%); imposed limits to number of treatments or to operating or postanesthetic room time (28%); and a lack of funds to purchase up to-date ECT or related anesthesiology equipment (14%). CONCLUSIONS: Electroconvulsive therapy is geographically accessible for most Canadians. Even when geography is not a factor, however, there are significant barriers to access resulting from inadequate availability of qualified professional staff, treatment areas, and funding. PMID- 21983756 TI - Electroconvulsive therapy and ethnicity. AB - Studies on ECT and race show that ECT clinics treat predominantly white patients. It has been suggested that certain ethnic groups are less likely to receive a diagnosis of an affective disorder and are therefore less likely to be referred to the ECT clinic. In the United States, inequalities in access to health care between the different ethnic groups may be a contributory factor. In the United Kingdom, there is a mistaken predominant perception that ECT is given mainly to members of ethnic minorities; instead, there is a need to ensure that nonwhites have equal access to this effective treatment. PMID- 21983757 TI - Continuation of ECT after recovery from transient, ECT-induced, postictal cortical blindness. AB - BACKGROUND: Transient, postictal cortical blindness is a rare adverse effect of electroconvulsive therapy (ECT). There is no information on the safety of continuation of ECT in patients who recover from ECT-induced cortical blindness. METHODS: An 18-year-old woman with paranoid schizophrenia experienced cortical blindness immediately after her first bifrontotemporal ECT treatment. There was complete, spontaneous recovery of vision after 6 hours. Neurological examination, computed tomography of the brain, and electroencephalographic study revealed no abnormality. A combination of circumstances suggested that continuation of ECT was desirable. After clearances from neurological and ophthalmological teams, she received 6 more ECT treatments, starting 9 days after the first. RESULTS: After resumption of ECT, there was marked improvement in psychopathology across the ECT course. There was no recurrence of visual symptoms. CONCLUSIONS: Patients who experience transient, ECT-induced, postictal cortical blindness may not necessarily experience the same adverse effect on rechallenge with ECT. PMID- 21983759 TI - Practice of electroconvulsive therapy in a tertiary care hospital in Pakistan. AB - OBJECTIVES: This study aimed to describe the practice of an unmodified electroconvulsive therapy (ECT) in a typical urban hospital setting in Pakistan. METHODS: This is a retrospective naturalistic study of patients who received ECT at Rawalpindi General Hospital between June 2000 and June 2008 by chart review. All useful data that could be retrieved from the charts were recorded. RESULTS: The process of administering ECT at the hospital is described. During the study period, of a total of 5240 patients who were admitted to the hospital, 1520 (29%) were administered ECT. Of these, 1352 (88.9%) did not get any kind of anesthesia during the procedure. The mean age of patients was 34.89 years, and the leading diagnoses were depression (60.8%), bipolar disorder (17.8%), and schizophrenia (9.1%). The mean number of ECTs received for these diagnoses were 5.78, 5.52, and 6.34, respectively. A total of 249 (16.7%) patients discontinued ECT against medical advice. CONCLUSIONS: In countries with limited resources, ECT is practiced in a markedly different way from more developed countries; although administering ECT without anesthesia is not desirable, in the face of severe economic constraints, it is often necessary. PMID- 21983758 TI - Effect of etomidate versus thiopental on major depressive disorder in electroconvulsive therapy, a randomized double-blind controlled clinical trial. AB - BACKGROUND: Although the therapeutic effect of electroconvulsive therapy (ECT) on major depressive disorder is widely investigated, there is a gap in literature regarding the possible effects of the medications used for induction of anesthesia in ECT. To the best of the authors' knowledge, this study is the first randomized double-blind clinical trial comparing the effect of etomidate and sodium thiopental on the depression symptoms in patients who have received ECT. METHODS: The participants of this study are 60 adult patients with major depressive disorder who were referred for ECT. They were randomly allocated into 1 of the 2 groups. One group received etomidate, and the other group received sodium thiopental, as medication for induction of anesthesia. All the patients received bilateral ECT. The outcomes measures included the Beck Depression Inventory score, seizure duration, and recovery duration after induction of anesthesia. RESULTS: The sex ratio and mean age were not different between the 2 groups. Linear regression analysis showed that etomidate decreased the depression score more than did sodium thiopental. Seizure duration in all of the sessions in the etomidate group was significantly higher than that of sodium thiopental group. CONCLUSIONS: In conclusion, etomidate may improve major depressive disorder more than sodium thiopental in patients who are receiving ECT. PMID- 21983760 TI - Improvement of asymmetrical temporal blood flow in refractory oral somatic delusion after successful electroconvulsive therapy. AB - Oral cenesthopathy is a somatic delusion in the oral area and categorized as delusional disorder, somatic type. Patients experience unusual and annoying sensations in the mouth such as pulling on the teeth, moving teeth, overly secreting mucus, tingling and pain, and so on, without a somatic base. The condition is usually treatment-resistant and impairs patients' quality of life. We report a case of oral cenesthopathy successfully treated with the modified electroconvulsive therapy, who demonstrated altered regional cerebral blood flow before and after the treatment detected by single-photon emission computed tomography. PMID- 21983761 TI - Electroconvulsive therapy in a terminally ill patient: when every day of improvement counts. AB - Electroconvulsive therapy (ECT) is seldom used in a palliative setting. Although literature on the application of ECT in terminally ill patients is sparse, ECT may be useful to rapidly improve the quality of life in these patients. We present the case of a 71-year-old man with metastasized pancreas carcinoma complicated by severe depression. After 3 ECT sessions, the communication between the patient and his family in the last moments of his life improved. We conclude that ECT should be considered to treat mood disorders in terminally ill patients when every day of improvement counts. PMID- 21983762 TI - Incremental effects of serum uric acid levels, autonomic dysfunction, and low grade inflammation on nocturnal blood pressure in untreated hypertensive patients and normotensive individuals. AB - OBJECTIVES: We aimed to evaluate the associations between nocturnal blood pressure (BP) and serum uric acid (SUA) level, low-grade inflammation, and cardiac autonomic function in untreated dipper and nondipper hypertensive patients and normotensive individuals. STUDY DESIGN: The study included 92 consecutive patients (44 men, 48 women; mean age 51.6 +/- 9.7 years) who presented for initial evaluation of hypertension. All patients underwent 24-hour Holter monitoring to assess heart rate variability (HRV) and ambulatory BP. Serum high-sensitivity C-reactive protein (hs-CRP) and SUA levels were measured. Due to the non-normal distribution of hs-CRP and microalbuminuria (MAU), they were normalized by logarithmic transformation. RESULTS: Of the study group, 60 patients (65.2%) were diagnosed as hypertensive (50% nondippers). In univariate correlation analysis, log(MAU) showed a significant correlation with nocturnal BP (r=0.560, p<0.001). Among HRV parameters, SDNN, SDANN, and triangular index were inversely correlated with log(hs-CRP) (r=-0.356, p=0.001; r=-0.350, p=0.001; r= 0.314, p=0.002, respectively) and nighttime BP (r=-0.286, p=0.006; r=-0.251, p=0.02; r=-0.294, p=0.004, respectively). Log(hs-CRP) was positively correlated with nighttime BP (r=0.302, p=0.003). Serum UA levels were correlated with only nocturnal BP; i.e., nocturnal mean (r=0.260, p=0.01), systolic (r=0.249, p=0.016), and diastolic BP (r=0.249, p=0.017). In multiple linear regression analysis, log(hs-CRP) and age were independent predictors of cardiac autonomic dysfunction, and log(hs-CRP), SUA, and HRV parameters were independent predictors of nocturnal BP measurements. CONCLUSION: Our findings suggest the role of low grade inflammation, uric acid levels, and autonomic dysfunction even in the early stages of hypertension. PMID- 21983764 TI - Impaired right ventricular functions in metabolic syndrome patients with preserved left ventricular ejection fraction. AB - OBJECTIVES: Metabolic syndrome (MetS) has been shown to be independently associated with increased risk for incident heart failure and coronary artery disease. We investigated whether there was deterioration in right ventricular functions in MetS patients with preserved left ventricular functions and its association with the number of MetS components. STUDY DESIGN: The study included 192 consecutive patients (148 women, 44 men; mean age 54.3 +/- 8.5 years) with the diagnosis of MetS based on the NCEP-ATP III criteria and 20 healthy controls (12 women, 8 men; mean age 51.6 +/- 8.4 years). All subjects underwent conventional and tissue Doppler (TDI) echocardiography to assess left and right ventricular functions, including right ventricular myocardial performance index (MPI) and tricuspid annular plane systolic excursion (TAPSE). RESULTS: The number of MetS components were three in 43.8%, four in 31.3%, and five in 25% of the patients. Right ventricular TDI-derived MPI was higher in patients with MetS compared to controls [median 0.5 (range 0.2-3.3) vs. 0.3 (0.1-0.7), p=0.000]. This was possibly due to significantly shortened right ventricular ejection time in MetS patients (p<0.05). Although TAPSE was within the normal range in MetS patients, it was significantly decreased compared to controls (p=0.000), accompanied by significantly lower TDI-derived S wave, E wave, and E/A ratio (p=0.000). None of the MetS components were significantly correlated with right ventricular TDI-derived MPI. There was no association between the number of MetS components and echocardiographic parameters. CONCLUSION: Our findings show that, despite preserved left ventricular systolic functions, both systolic and diastolic functions of the right ventricle deteriorate in MetS patients. PMID- 21983763 TI - In-hospital prognostic value of admission plasma B-type natriuretic peptide levels in patients undergoing primary angioplasty for acute ST-elevation myocardial infarction. AB - OBJECTIVES: We assessed in-hospital prognostic value of admission plasma B-type natriuretic peptide (BNP) levels in patients undergoing primary percutaneous coronary intervention (p-PCI) for acute ST-elevation myocardial infarction (STEMI). STUDY DESIGN: In a retrospective design, we evaluated 992 patients (801 males, 191 females; mean age 56 +/- 12 years) treated with p-PCI for STEMI. The patients were divided into two groups according to the admission BNP levels, taking the cut-off value of BNP as 100 pg/ml; i.e, >= 100 pg/ml (n=334, 33.7%) and <100 pg/ml (n=658, 66.3%). Postprocedural angiographic and clinical in hospital results were recorded. RESULTS: No-reflow (24% vs. 9%), heart failure (32.3% vs. 5.5%) and death (15.6% vs. 1.7%) were significantly more common in patients with BNP >= 100 pg/ml (p<0.001). In multivariate analysis, elevated baseline BNP level was identified as an independent predictor of no-reflow (OR=1.83; 95% CI 1.22-2.74, p=0.003), acute heart failure (OR=2.67; 95% CI 1.55 4.58, p<0.001), and in-hospital mortality (OR=3.28; 95% CI 1.51-7.14, p=0.003). In receiver operating characteristic curve analysis, the area under the curve and sensitivity/specificity of the cut-off value of BNP (100 pg/ml) for prediction of clinical endpoints were 0.741 and 58.6%/70.3% for no-reflow, 0.822 and 75%/73.3% for heart failure, and 0.833 and 82.5%/69.4% for death, respectively (p<0.001 for all). CONCLUSION: Elevated admission BNP level is an independent predictor of angiographic no-reflow, acute heart failure, and mortality in STEMI patients during in-hospital period, suggesting that it might be incorporated into traditional risk scoring systems to improve early risk stratification. PMID- 21983765 TI - Increased aortic pulse wave velocity in obese children. AB - OBJECTIVES: Obesity may start in childhood and obese children are more likely to grow up to be obese adults. Atherosclerosis is one of the most important complications of obesity. Pulse wave velocity (PWV), a noninvasive measure of arterial stiffness, is accepted to be an indicator of subclinical atherosclerosis. The aim of the study was to determine PWV in obese children. STUDY DESIGN: The study included 30 obese (12 boys, 18 girls; mean age 13 +/- 2 years) and 30 lean children (13 boys, 17 girls; mean age 12.5 +/- 1.7 years). Weight and height were measured and obesity was defined as body mass index (BMI) of greater than the 95th percentile for age. All the subjects underwent echocardiographic evaluation and blood samples were obtained. Pulse-wave velocity was calculated using the following equation: PWV (m/sec) = height-based aortic length (cm)/(100xtransit time [sec]). The latter was measured as the difference in the time of onset of two flows at the diaphragm and the aortic valve. RESULTS: Obese subjects had significantly higher blood pressure levels compared to the control group (p<0.001). The two groups were similar with respect to fasting glucose, hemoglobin, serum creatinine, and lipid levels. Among echocardiographic parameters, left ventricular end-diastolic dimension, interventricular septum thickness, posterior wall thickness, left ventricular mass index, left atrium dimension, and aortic root dimension were significantly increased in obese subjects compared to controls (p<0.01). Obese children had significantly higher PWV values than the controls (4.0 +/- 0.8 vs. 3.3 +/- 0.7 m/sec, p<0.001). A positive significant correlation was found between PWV and BMI (r=0.391, p=0.002). CONCLUSION: Our findings show that aortic PWV is increased in obese children, suggesting that obesity may cause subclinical atherosclerosis even at early ages. PMID- 21983766 TI - [Comparative effects of nebivolol and valsartan on atrial electromechanical coupling in newly diagnosed stage 1 hypertensive patients]. AB - OBJECTIVES: Hypertension is an important cardiovascular risk factor for the development of atrial fibrillation (AF). Increased atrial electromechanical coupling time interval measured by tissue Doppler is accepted as an important factor for prediction of AF development in hypertensive patients. The aim of this study was to compare the effects of valsartan, an angiotensin receptor blocker, and nebivolol, a beta-blocker, on atrial electromechanical coupling in newly diagnosed stage 1 hypertensive patients. STUDY DESIGN: The study included 60 newly diagnosed stage 1 hypertensive patients with no other systemic disease. The patients were randomized to receive nebivolol 5 mg (30 patients; 21 women, 9 men; mean age 48.4 +/- 11.4 years) and valsartan 160 mg (30 patients; 21 women, 9 men; mean age 49.8 +/- 11.3 years). All the patients underwent tissue Doppler echocardiographic examination before and three months after treatment to compare the effects of the two drugs on atrial electromechanical coupling. RESULTS: Baseline blood pressures, electrocardiographic and echocardiographic findings, and atrial electromechanical coupling were similar in both groups (p>0.05). Both drugs significantly reduced blood pressure after treatment, with similar efficacy (p>0.05). Atrial electromechanical coupling time intervals showed significant decreases in both groups. CONCLUSION: Prolonged interatrial electromechanical time intervals in hypertensives are improved with antihypertensive treatment. PMID- 21983767 TI - [Usefulness of high-sensitivity CRP increases during circadian rhythm for prediction of long-term cardiovascular events in patients with stable coronary artery disease]. AB - OBJECTIVES: We investigated the value of circadian variations in high-sensitivity C-reactive protein (hs-CRP) levels in prediction of long-term cardiovascular events (CVE) in patients with stable coronary artery disease (CAD). STUDY DESIGN: The study included 94 patients (70 men, 24 women; mean age 58 +/- 9 years) with stable CAD. High-sensitivity CRP levels were measured at six-hour intervals, namely, morning (06:00), midday (12:00), evening (18:00), and midnight (24:00). Absolute change in hs-CRP (absolute DeltaCRP) was calculated by subtracting the midday hs-CRP level from that of the morning. Relative change in hs-CRP (relative DeltaCRP) was calculated by dividing absolute DeltaCRP by the midday hs-CRP level. The patients were followed-up for a mean of 40.2 +/- 8.0 months for monitoring of CVE. RESULTS: During the follow-up period, CVE occurred in 24 patients (25.5%). Patients who developed CVE exhibited significantly higher serum creatinine, B-type natriuretic peptide, morning, evening, and midnight hs-CRP levels, absolute and relative DeltaCRP, and left atrial end-diastolic diameter compared to patients without CVE (p<0.05). In logistic regression analysis, only left atrial end-diastolic diameter and absolute DeltaCRP were independent predictors of CVE (OR=1.11, 95% CI 1.003-1.236, p=0.044 and OR=1.58, 95% CI 1.195 2.090, p=0.001, respectively). Every 1 mg/l increase in absolute DeltaCRP represented a 58.1% increase in CVE risk. In receiver operating characteristics curve analysis, the cut-off value of 2 mg/l for absolute DeltaCRP predicted CVE with 89.5% sensitivity and 84.2% specificity. CONCLUSION: Our findings suggest that absolute circadian increases in hs-CRP levels may be helpful in predicting long-term CVEs in patients with stable CAD. PMID- 21983768 TI - Intercoronary continuity between the right and circumflex coronary arteries causing myocardial ischemia. AB - Intercoronary continuity refers to a bidirectional flow in patients with normal coronary arteries. Although such connections have been proposed to have a protective role against potential obstructive coronary artery disease, their functional significance is unclear. We report on a 53-year-old woman who presented with typical chest pain. Exercise myocardial perfusion imaging revealed perfusion defects involving the basal regions of the inferior and inferoseptal walls. Coronary angiography showed an intercoronary continuity between the right coronary artery and circumflex artery. Following institution of medical therapy, the patient's complaint improved and she had no complaint during one-year follow up. This is the first reported case in which an intercoronary continuity was associated with myocardial ischemia. PMID- 21983769 TI - Successful percutaneous epicardial ablation of an accessory pathway located at the right atrial appendage. AB - In patients with Wolff-Parkinson-White syndrome, difficulty in ablation of accessory pathways is associated with failures and recurrences. Epicardially located accessory pathways may require different management strategies when conventional ablation attempts fail. In particular, an epicardial accessory pathway communicating the right atrial appendage to the right ventricle is an extraordinary situation resulting in difficulties in ablation. Hereby, we report on a challenging case of percutaneous epicardial ablation of an epicardial accessory pathway located at right atrial appendage in a 28-year-old man with Wolff-Parkinson-White syndrome, who had a prior history of unsuccessful endocardial ablation. Percutaneous epicardial ablation may be a viable option obviating the necessity of surgical ablation procedures for difficult ablation cases with epicardial accessory pathways. PMID- 21983770 TI - Agitated saline contrast use in a case with peripheral pulmonary artery stenosis. AB - We present a case of peripheral pulmonary artery stenosis that was incidentally detected by agitated saline contrast study. A 19-year-old male patient underwent cardiologic examination to determine suitability for military service. He had exertional intolerance since early childhood. Physical examination showed a murmur over the entire right hemithorax. Echocardiography showed moderately enlarged right ventricle, right atrium, and main pulmonary artery, and color Doppler showed mild tricuspid regurgitation. Right ventricular systolic pressure was estimated as 55-60 mmHg from the tricuspid regurgitation jet. For further evaluation of the systolic murmur, agitated saline contrast echocardiography was performed. During continuous wave Doppler examination while there were remnants of bubbles in the right heart and pulmonary vascular bed, a systolodiastolic flow with a peak gradient of 30 mmHg was noted. After disappearance of the bubbles, the signal was not detectable. Repeat agitated saline contrast examination again showed a gradient of 35 mmHg. A stenosis in the distal branches of the right pulmonary artery was suspected. Finally, computed tomography revealed multiple stenoses in the pulmonary vascular bed. To our best knowledge, this is the first case in which agitated saline contrast examination enabled the diagnosis of peripheral pulmonary artery stenosis. PMID- 21983771 TI - Acute thrombus formation on an Amplatzer device during transcatheter closure of an atrial septal defect in a patient with homozygous factor V Leiden mutation. AB - A 32-year-old woman underwent transcatheter closure of a secundum type atrial septal defect with the Amplatzer device. The procedure was started under premedication with aspirin, clopidogrel, and heparin. During the procedure, a highly mobile thrombus attached to the left atrial disc of the device was detected by transesophageal echocardiography (TEE). The device and the associated thrombus were successfully withdrawn and the patient was started on a combination of heparin and tirofiban infusion. The procedure was successfully completed without any recurrent thrombus formation or residual shunt. Further investigation for thrombophilia revealed homozygous factor V Leiden mutation and the patient was started on a life-long warfarin therapy. Follow-up TEE showed proper device position with no recurrent thrombus and the follow-up was uneventful. PMID- 21983772 TI - [Development of biventricular large apical thrombi and cerebral embolism in a young woman with peripartum cardiomyopathy]. AB - Peripartum cardiomyopathy is a rare cardiac disorder. Although left ventricular apical thrombus formation is common in peripartum cardiomyopathy, biventricular apical thrombi formation is a very rare condition in these patients. A 21-year old woman presented with complaints of dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and palpitations that appeared three months after labor. Transthoracic echocardiography showed severe global hypokinesis, decreased left and right ventricular ejection fraction (left 30%, right 35%), increased left ventricular end-diastolic dimension (60 mm), grade 2 mitral regurgitation, and biventricular apical thrombi. On the second day of admission, she developed global aphasia and right hemiplegia. The patient was successfully treated with recombinant tissue plasminogen activator. Transthoracic echocardiography following treatment showed disappearance of biventricular apical thrombi. She had no neurologic deficit. Treatment for heart failure was continued due to persistence of global hypokinesis and left ventricular dilatation. PMID- 21983773 TI - [A rare cause of recurrent wheezing and respiratory distress: Scimitar syndrome]. AB - Scimitar syndrome is characterized by partial or total anomalous pulmonary venous return from the right lung. We present a 15-month-old boy who was diagnosed with Scimitar syndrome after examinations for recurrent wheezing and respiratory distress. The chest radiograph showed a scimitar sign in the right hemithorax, obscuring the contours of the right atrium. Echocardiography showed dilatation of the right heart cavities and increased flow in the inferior vena cava, without a cardiac abnormality. The patient underwent cardiac catheterization for radiographic and hemodynamic evaluations, during which a scimitar vein was detected, draining the right pulmonary veins to the inferior vena cava. Coil occlusion was performed on the abnormal artery arising from the infradiaphragmatic aorta. The patient was referred to surgery for repair of the anomalous pulmonary venous return and resection of the sequestered pulmonary segment. PMID- 21983774 TI - Almanac 2011: stable coronary artery disease. The national society journals present selected research that has driven recent advances in clinical cardiology. PMID- 21983775 TI - Almanac 2011: heart failure. The national society journals present selected research that has driven recent advances in clinical cardiology. PMID- 21983776 TI - [Suggestions on how to do: follow-up of a patient with permanent pacemaker]. PMID- 21983777 TI - Double-orifice mitral valve. PMID- 21983778 TI - Subvalvular pulmonary stenosis, right ventricular hypertrophy and patent foramen ovale. PMID- 21983779 TI - Surgical repair of interrupted aorta and ascending aortic aneurysm. PMID- 21983780 TI - Incidental detection of pulmonary hamartoma by echocardiography. PMID- 21983781 TI - Two cases of Noonan syndrome: aortic coarctation causing a giant aneurysm of the descending aorta. PMID- 21983782 TI - Which aerococcus? comment on: an unusual microorganism, aerococcus viridans, causing endocarditis and aortic valvular obstruction due to a huge vegetation (turk kardiyol dern ars 2011;39:317-9). PMID- 21983783 TI - A primary microcephaly protein complex forms a ring around parental centrioles. AB - Autosomal recessive primary microcephaly (MCPH) is characterized by a substantial reduction in prenatal human brain growth without alteration of the cerebral architecture and is caused by biallelic mutations in genes coding for a subset of centrosomal proteins. Although at least three of these proteins have been implicated in centrosome duplication, the nature of the centrosome dysfunction that underlies the neurodevelopmental defect in MCPH is unclear. Here we report a homozygous MCPH-causing mutation in human CEP63. CEP63 forms a complex with another MCPH protein, CEP152, a conserved centrosome duplication factor. Together, these two proteins are essential for maintaining normal centrosome numbers in cells. Using super-resolution microscopy, we found that CEP63 and CEP152 co-localize in a discrete ring around the proximal end of the parental centriole, a pattern specifically disrupted in CEP63-deficient cells derived from patients with MCPH. This work suggests that the CEP152-CEP63 ring-like structure ensures normal neurodevelopment and that its impairment particularly affects human cerebral cortex growth. PMID- 21983785 TI - Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3. AB - We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R, ASIP and MTAP-CDKN2A. We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 * 10(-11), OR in combined replication cohorts of 0.89 (95% CI 0.85-0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 * 10(-8)). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1. Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density. PMID- 21983786 TI - Identification of low-frequency variants associated with gout and serum uric acid levels. AB - We tested 16 million SNPs, identified through whole-genome sequencing of 457 Icelanders, for association with gout and serum uric acid levels. Genotypes were imputed into 41,675 chip-genotyped Icelanders and their relatives, for effective sample sizes of 968 individuals with gout and 15,506 individuals for whom serum uric acid measurements were available. We identified a low-frequency missense variant (c.1580C>G) in ALDH16A1 associated with gout (OR = 3.12, P = 1.5 * 10( 16), at-risk allele frequency = 0.019) and serum uric acid levels (effect = 0.36 s.d., P = 4.5 * 10(-21)). We confirmed the association with gout by performing Sanger sequencing on 6,017 Icelanders. The association with gout was stronger in males relative to females. We also found a second variant on chromosome 1 associated with gout (OR = 1.92, P = 0.046, at-risk allele frequency = 0.986) and serum uric acid levels (effect = 0.48 s.d., P = 4.5 * 10(-16)). This variant is close to a common variant previously associated with serum uric acid levels. This work illustrates how whole-genome sequencing data allow the detection of associations between low-frequency variants and complex traits. PMID- 21983784 TI - Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease. AB - More than 1,000 susceptibility loci have been identified through genome-wide association studies (GWAS) of common variants; however, the specific genes and full allelic spectrum of causal variants underlying these findings have not yet been defined. Here we used pooled next-generation sequencing to study 56 genes from regions associated with Crohn's disease in 350 cases and 350 controls. Through follow-up genotyping of 70 rare and low-frequency protein-altering variants in nine independent case-control series (16,054 Crohn's disease cases, 12,153 ulcerative colitis cases and 17,575 healthy controls), we identified four additional independent risk factors in NOD2, two additional protective variants in IL23R, a highly significant association with a protective splice variant in CARD9 (P < 1 * 10(-16), odds ratio ~ 0.29) and additional associations with coding variants in IL18RAP, CUL2, C1orf106, PTPN22 and MUC19. We extend the results of successful GWAS by identifying new, rare and probably functional variants that could aid functional experiments and predictive models. PMID- 21983788 TI - A chiral tetragonal magnesium-carboxylate framework with nanotubular channels. AB - Reported here is a rare example of a highly symmetrical chiral Mg-based MOF (CPF 1) with nanotubular channels, built from 4(1) (or 4(3)) helical chains. It exhibits a high gas sorption capacity (ca. 1.29 wt% H(2) at 77 K, 1 atm; 84 cm(3) g(-1) of CO(2) at 273 K, 1 atm). PMID- 21983790 TI - Mid-to-long term follow-up of Transcend metal-on-metal versus Interseal metal-on polyethylene bearings in total hip arthroplasty. AB - Second-generation metal-on-metal total hip arthroplasty (THA) was introduced in the early 1990s to address osteolysis and aseptic loosening resulting from polyethylene wear. We present a comparison between the Transcend metal-on-metal and Interseal metal-on-polyethylene THAs. Thirty-seven hips with Transcend metal bearings and 36 hips with Interseal polyethylene acetabular liners but identical acetabular shells were reviewed to determine clinical performance, radiographic changes, and survivorship. Patients with higher anticipated activity levels were selected to receive the Transcend bearing. Mean follow-up time was 107.0 months for the Transcend group, and 90.4 months for the Interseal group. There were no significant differences between the Transcend and Interseal groups for mode of failure and survivorship, which is notable considering the younger and more active Transcend group. However, the Transcend group showed significantly better clinical scores, which may have been a result of the selection methods. Neither surface was differentially implicated in osteolysis, aseptic loosening, or adverse local tissue reaction (ALTR). Our study shows a favorable and comparable performance for both systems. PMID- 21983791 TI - In vivo response of bone defects filled with PMMA in an ovine model. AB - The use of PMMA cement is common in arthroplasty for cemented fixation and defect filling. Concerns remain regarding effects of cement curing temperature on the viability of cancellous bone. In this study we filled surgically-created defects (mean volume 0.585+/-0.251 mL) in the cancellous bone of the distal femur and proximal tibia of 6 sheep with PMMA and measured temperature changes in surrounding bone whilst the cement cured, using 3 thermocouples per defect. Animals were euthanised at 3 (n=3) and 12 (n=3) weeks postoperatively and the bone-cement interface assessed histologically. Despite mean maximum temperatures of 49.3+/-10.2 degrees C (range: 40.9 degrees C - 82.2 degrees C) thermonecrosis was not a common histological feature at either timepoint. The exposure of bone to high cement temperatures in this study has not led to bone necrosis and/or tissue damage. PMID- 21983793 TI - Cation-dependent nutrient transport in shrimp digestive tract. AB - Purified epithelial brush border membrane vesicles (BBMV) were produced from the hepatopancreas of the Atlantic White shrimp, Litopeneaus setiferus, using standard methods originally developed for mammalian tissues and previously applied to other crustacean and echinoderm epithelia. These vesicles were used to study the cation dependency of sugar and amino acid transport across luminal membranes of hepatopancreatic epithelial cells. (3)H-D: -glucose uptake by BBMV against transient sugar concentration gradients occurred when either transmembrane sodium or potassium gradients were the only driving forces for sugar accumulation, suggesting the presence of a possible coupled transport system capable of using either cation. (3)H-L: -histidine transport was only stimulated by a transmembrane potassium gradient, while (3)H-L: -leucine uptake was enhanced by either a sodium or potassium gradient. These responses suggest the possible presence of a potassium-dependent transporter that accommodates either amino acid and a sodium-dependent system restricted only to L: -leucine. Uptake of (3)H-L: -leucine was significantly stimulated (P < 0.05) by several metallic cations (e.g., Zn(2+), Cu(2+), Mn(2+), Cd(2+), or Co(2+)) at external pH values of 7.0 or 5.0 (internal pH 7.0), suggesting a potential synergistic role of the cations in the transmembrane transfer of amino acids. (3)H-L: -histidine influxes (15 suptakes) were hyperbolic functions of external [zinc] or [manganese], following Michaelis-Menten kinetics. The apparent affinity constant (e.g., K (m)) for manganese was an order of magnitude smaller (K (m) = 0.22 MUM Mn) than that for zinc (K (m) = 1.80 MUM Zn), while no significant difference (P > 0.05) occurred between their maximal transport velocities (e.g., J (max)). These results suggest that a number of cation-dependent nutrient transport systems occur on the shrimp brush border membrane and aid in the absorption of these important dietary elements. PMID- 21983787 TI - Genome-wide association study identifies three new melanoma susceptibility loci. AB - We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 * 10( 9)), an SNP in MX2 (rs45430, P = 2.9 * 10(-9)) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 * 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 * 10(-7) under a fixed-effects model and P = 1.2 * 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series. PMID- 21983794 TI - Using real-time fMRI to learn voluntary regulation of the anterior insula in the presence of threat-related stimuli. AB - Previous studies have shown that healthy participants learn to control local brain activity with operant training by using real-time functional magnetic resonance imaging (rt-fMRI). Very little data exist, however, on the dynamics of interaction between critical brain regions during rt-fMRI-based training. Here, we examined self-regulation of stimulus-elicited insula activation and performed a psychophysiological interaction (PPI) analysis of real-time self-regulation data. During voluntary up-regulation of the left anterior insula in the presence of threat-related pictures, differential activations were observed in the ventrolateral prefrontal cortex, the frontal operculum, the middle cingulate cortex and the right insula. Down-regulation in comparison to no-regulation revealed additional activations in right superior temporal cortex, right inferior parietal cortex and right middle frontal cortex. There was a significant learning effect over sessions during up-regulation, documented by a significant improvement of anterior insula control over time. Connectivity analysis revealed that successful up-regulation of the activity in left anterior insula while viewing aversive pictures was directly modulated by dorsomedial and ventrolateral prefrontal cortex. Down-regulation of activity was more difficult to achieve and no learning effect was observed. More extensive training might be necessary for successful down-regulation. These findings illustrate the functional interactions between different brain areas during regulation of anterior insula activity in the presence of threat-related stimuli. PMID- 21983796 TI - High cortisol levels are associated with low quality food choice in type 2 diabetes. AB - Hypothalamic-pituitary-adrenal (HPA) axis control may be impaired in type 2 diabetes (T2DM). Glucocorticoids increase consumption of low quality foods high in calories, sugar, and fat. We explored the relationship between cortisol levels, poor blood glucose control, and food quality choice in T2DM. Twenty-seven healthy controls were age-, gender- and education-matched to 27 T2DM participants. Standard clinical blood tests and cortisol values were measured from fasting blood samples. Participants recorded all consumed food and drink items in a consecutive 3-day food diary. Diaries were analyzed for "high quality" and "low quality" foods using a standardized method with high reliability (0.97 and 0.86, respectively). Controlling for education, body mass index (BMI) and hemoglobin A1C (HbA1C), log-transformed cortisol (LogC) predicted the percent of low quality foods (R (2) = 0.092, beta = 0.360, P < 0.05), but not the percent of high quality foods chosen. Controlling for education, BMI, and LogC, HbA1C significantly predicted both the percent of low quality foods (DeltaR (2) = 0.079, beta = 0.348, P = 0.024) and high quality foods chosen (DeltaR (2) = 0.085, beta = -0.362, P = 0.022). The relationship between HbA1C and low quality food choice may be mediated by cortisol, controlling for BMI and education (P < 0.01). HbA1C displayed both an indirect (cortisol-mediated) effect (P < 0.05) and direct effect on low quality food choice (P < 0.05). The relationship between HbA1C and low quality food choice may be partially mediated by cortisol. Poor blood glucose control may cause HPA axis disruption, increased consumption of low quality foods. PMID- 21983797 TI - Time course responses of serum GH, insulin, IGF-1, IGFBP1, and IGFBP3 concentrations after heavy resistance exercise in trained and untrained men. AB - To investigate the effect of heavy resistance exercise on IGF-1 system, 19 healthy trained men and 15 healthy untrained men volunteered to participate in this study. The subjects were randomly divided into experimental and control groups. Subjects of experimental groups were forced to perform a heavy resistance exercise with the intensity of 70-80% of 1RM in selected movements. The blood samples were taken from all subjects four times; before (T1), immediately after (T2), 5 (T3), and 8 (T4) hours after exercise. Analysis of data showed that a session of heavy resistance exercise induced significant increase in GH at T2 (P < 0.05) and a significant decrease in insulin at T4 (P < 0.05) and a significant decrease in IGFBP3 at T4 (P < 0.05) in trained group. In untrained group, no significant change in any of the variables was observed. However, the procedure of response in variables was almost similar in two experimental groups. Although, the exercise did not appreciably affect IGF-1 levels, it decreased in all groups at length of time after exercise. In addition, the exercise did not have any notable effect on IGFBP1 levels over time. In conclusion, the findings of this study indicate that the intense resistance exercise can lead to changes in blood concentrations of IGF-1 system components which are observable in blood circulation over time and the amounts of changes depend on subjects' fitness levels and exercise variables. PMID- 21983795 TI - Regional bone metabolism at the lumbar spine and hip following discontinuation of alendronate and risedronate treatment in postmenopausal women. AB - The aim of this study was to examine the effects of bisphosphonate discontinuation on bone metabolism at the spine and hip measured using (18) F fluoride PET. Bone metabolism at the spine remained stable following discontinuation of alendronate and risedronate at 1 year but increased in the hip in the alendronate group only. INTRODUCTION: Bisphosphonates such as alendronate (ALN) or risedronate (RIS) have persistent effects on spine BMD following discontinuation. METHODS: Positron emission tomography (PET) was used to examine regional bone metabolism in 20 postmenopausal women treated with ALN (n = 11) or RIS (n = 9) for a minimum of 3 years at screening (range 3-9 years, mean 5 years for both groups). Subjects underwent a dynamic scan of the lumbar spine and a static scan of both hips at baseline and 6 and 12 months following treatment discontinuation. (18) F-fluoride plasma clearance (K(i)) at the spine was calculated using a three-compartment model. Standardised uptake values (SUV) were calculated for the spine, total hip, femoral neck and femoral shaft. Measurements of BMD and biochemical markers of bone turnover were also performed. RESULTS: With the exception of a significant decrease in spine BMD in the ALN group, BMD remained stable. Bone turnover markers increased significantly from baseline by 12 months for both study groups. Measurements of K(i) and SUV at the spine and femoral neck did not change significantly in either group. SUV at the femoral shaft and total hip increased significantly but in the ALN group only, increasing by 33.8% (p = 0.028) and 24.0% (p = 0.013), respectively. CONCLUSIONS: Bone metabolism at the spine remained suppressed following treatment discontinuation. A significant increase in SUV at the femoral shaft and total hip after 12 months was observed but for the ALN group only. This study was small, and further clinical studies are required to fully evaluate the persistence of BP treatment. PMID- 21983798 TI - Evaluation of dysphagia after cervical surgery using laryngeal electromyography. AB - The purpose of this study was to investigate the causes of dysphagia after cervical surgery using laryngeal electromyography (LEMG), and the effect of laryngeal neuropathy on the severity of dysphagia. Seventeen patients with dysphagia evident after cervical surgery were included. Video fluoroscopic swallow study (VFSS) parameters evaluated included the volume of residue in the vallecular pouch and the pyriform sinus, the Rosenbek penetration-aspiration scale (PAS), and the swallowing function scoring system (SFSS). By VFSS findings, patients were classified into a mild or severe dysphagia group. Nine of 17 patients showed voice change. SFSS scores were 0 in 2 patients, 3 in 1 patient, 4 in 1 patient, 5 in 1 patient, and 6 in 12 patients. PAS scores were 1 in 8 patients, 2 in 5 patients, 7 in 3 patients, and 8 in 1 patient. Laryngeal neuropathy was evident in seven patients (41.2%). Of these, all patients exhibited recurrent laryngeal neuropathy and 28.6% had superior laryngeal neuropathy. When we evaluated LEMG findings with respect to the severity of dysphagia, the severe dysphagia group showed significant association with the presence of laryngeal neuropathy (p = 0.006). Although the level of residue in the vallecular pouch was not associated with the presence of laryngeal neuropathy (p = 0.442), the amount of residue in the pyriform sinus did show a significant association (p = 0.020). PMID- 21983799 TI - Change in HIV-HCV risk-taking behavior and seroprevalence among opiate users seeking treatment over an 11-year period and harm reduction policy. AB - Our purpose was to assess change in HIV and HCV prevalence and risk-taking behaviors among IDUs over a period of time that included changes in French Public Health policy. Risk behavior and biological testing for serostatus were collected from cross-sectional samples of yearly new requests for opiate dependence treatment in Aquitaine, France between 1994 and 2004 (n = 648). Coincident declines in injection equipment sharing and HIV prevalence among injectors were observed, while sexual behavior remained stable. There was a decline in HCV prevalence that was not significant among injectors. After controlling for potential confounding variables, participants enrolled after 1995 were less likely to share injection material and those enrolled after 1999 were less likely to share spoons. Our findings give evidence for behavioral and seroprevalence changes among IDUs over a period of time that included changes in needle access policy. PMID- 21983800 TI - Using digital communication technology fails to improve longitudinal evaluation of an HIV prevention program aimed at Indian truck drivers and cleaners. AB - HIV prevention programs for truck drivers and cleaners (TDC) in India are limited. Longitudinal follow-up presents an obstacle to program effectiveness evaluation. We asked 3,028 TDC in a truck-driver HIV prevention program in Hyderabad to leave a cellular telephone number; we contacted participants 6 months after the intervention to assess sexual risk behavior change. Married, older, and better educated participants were more likely to leave phone numbers. Only 6.5% of TDC were reachable after 6 months. Longitudinal follow-up of this mobile sub-population remains a challenge, and more effective methods for evaluating HIV prevention programs are needed. PMID- 21983801 TI - Early onset of coronary heart disease in a young woman with familial hypercholesterolemia: coronary findings and effect of short term treatment with high dose atorvastatin. AB - We describe the case of a 22-year old woman affected by familial hypercholesterolemia, referred for chest pain and treated with angioplasty of left anterior descending coronary artery. Marked systemic inflammation associated with acute coronary syndrome was reduced by 1-month therapy with high dose atorvastatin. PMID- 21983802 TI - Molecular simulation of water removal from simple gases with zeolite NaA. AB - Water vapor removal from some simple gases using zeolite NaA was studied by molecular simulation. The equilibrium adsorption properties of H(2)O, CO, H(2), CH(4) and their mixtures in dehydrated zeolite NaA were computed by grand canonical Monte Carlo simulations. The simulations employed Lennard-Jones + Coulomb type effective pair potential models, which are suitable for the reproduction of thermodynamic properties of pure substances. Based on the comparison of the simulation results with experimental data for single-component adsorption at different temperatures and pressures, a modified interaction potential model for the zeolite is proposed. In the adsorption simulations with mixtures presented here, zeolite exhibits extremely high selectivity of water to the investigated weakly polar/non-polar gases demonstrating the excellent dehydration ability of zeolite NaA in engineering applications. PMID- 21983803 TI - The physiology of the normal human breast: an exploratory study. AB - The physiology of the nonlactating human breast likely plays a key role in factors that contribute to the etiology of breast cancer and other breast conditions. Although there has been extensive research into the physiology of lactation, few reports explore the physiology of the resting mammary gland, including mechanisms by which compounds such as hormones, drugs, and potential carcinogens enter the breast ducts. The purpose of this study was to explore transport of exogenous drugs into ductal fluid in nonlactating women and determine if their concentrations in the fluid are similar to those observed in the breast milk of lactating women. We selected two compounds that have been well characterized during lactation, caffeine and cimetidine. Caffeine passively diffuses into breast milk, but cimetidine is actively transported and concentrated in breast milk. After ingestion of caffeine and cimetidine, 14 nonlactating subjects had blood drawn and underwent ductal lavage at five time points over 12 h to measure drug levels in the fluid and blood. The concentrations of both caffeine and cimetidine in lavage fluid were substantially less than those observed in breast milk. Our results support recent evidence that the cimetidine transporter is not expressed in the nonlactating mammary gland, and highlight intriguing differences in the physiology and molecular transport of the lactating and nonlactating breast. The findings of this exploratory study warrant further exploration into the physiology of the nonlactating mammary gland to elucidate factors involved in disease initiation and progression. PMID- 21983804 TI - The biochemistry of ketogenesis and its role in weight management, neurological disease and oxidative stress. AB - Ketogenesis is the branch of mammalian metabolism concerned with the synthesis of ketone bodies. In this process, the small, water-soluble compounds acetoacetate, D-3-beta-hydroxybutyrate and propanone are produced by the liver in response to reduced glucose availability. Although ketone bodies are always present at a low level in healthy individuals, dietary manipulation and certain pathological conditions can increase the levels of these compounds in vivo. In some instances, such as in refractory epilepsy, high levels of ketone bodies can be beneficial-in this instance, by exerting an anticonvulsant effect. Conversely, if the levels of ketones rise to supraphysiological levels, as can occur in diabetes mellitus, a state of ketoacidosis can occur, which has serious consequences for cellular function. More recently, research has identified a possible link between ketogenesis and free radical-mediated pathologies, highlighting the potential application of ketogenic diets to the treatment of conditions such as Alzheimer's disease. Overall, an understanding of ketone body metabolism and its links to human disease may prove to be vital in developing new regimens for the treatment of human disease. PMID- 21983805 TI - Effects of Greek legume plant extracts on xanthine oxidase, catalase and superoxide dismutase activities. AB - Legumes are considered to have beneficial health implications, which have been attributed to their phytochemical content. Polyphenols are considered the most important phytochemical compounds extensively studied for their antioxidant properties. The aim of the present study was to examine the effects of potent antioxidant legume plant extracts on xanthine oxidase (XO), catalase (CAT) and superoxide dismutase (SOD) activities. XO exerts a dual role, as it is the major contributor of free radicals during exercise while it generates uric acid, the most potent antioxidant molecule in plasma. CAT and SOD are two of the main enzymes of the antioxidant defence of tissues. We demonstrate that the majority of the extracts inhibited XO activity, but they had no effect on CAT inhibition and SOD induction when used at low concentrations. These results imply that the tested extracts may be considered as possible source of novel XO inhibitors. However, we have shown that allopurinol administration, a known XO inhibitor, before exercise reduces performance and induces oxidative stress in rats. Considering the fact that the extracts examined had an inhibitory effect on XO activity, possibly posing a restriction in their characterization as antioxidants, phytochemical antioxidant administration before exercise should probably be reconsidered. PMID- 21983806 TI - Antioxidant-rich date palm fruit extract inhibits oxidative stress and nephrotoxicity induced by dimethoate in rat. AB - Recent investigations have proved the crucial role of nutritional antioxidants to prevent the damage caused by toxic compounds. In this study, the antioxidant effect of date palm fruit extract on dimethoate-induced oxidative stress and nephrotoxicity in rat is investigated and compared with the effect of the well known antioxidant vitamin C. Male Wistar rats were randomly divided into six groups of ten each: a control group (C), a group that received dimethoate (20 mg/kg body weight) (D), a group given Deglet Nour extract (DNE), a group treated with DNE 30 min before the administration of dimethoate (DNE + D), a group which received VitC (100 mg/kg body weight) plus dimethoate (Vit C + D), and a group given dimethoate for the first month and DNE 30 min after administration of dimethoate, during the second month (D + DNE). These components were daily administered by gavage for 2 months. After completing the treatment period, blood samples from rats were collected under inhaled diethyl ether anesthesia for serum urea, uric acid, and creatinine levels, while the rat kidneys were obtained for enzyme assays and histology. Oral administration of dimethoate in rats induced a marked renal failure characterized by a significant increase in serum creatinine and urea levels (p < 0.01) in addition to a significant decrease in serum uric acid (p < 0.05). Interestingly, these drastic modifications were accompanied by a marked enhancement of lipid peroxidation in kidney, indicating a significant induction of oxidative damage (p < 0.01) and dysfunctions of enzymatic antioxidant defenses. These biochemical alterations were also accompanied by histological changes in kidney revealed by a narrowed Bowman's space, tubular degeneration, tubular cell desquamation, and tubular dilatation of proximal tubules. Treatment with date palm fruit extract (Deglet Nour) and also with vitamin C significantly (p < 0.05) reversed the serum renal markers to their near normal levels when compared with dimethoate-treated rats. In addition, Deglet Nour extract and vitamin C significantly reduced lipid peroxidation, restored the antioxidant defense enzymes in the kidney, and improved the histopathology changes. The present findings indicate that in vivo date palm fruit may be useful for the prevention of oxidative stress-induced nephrotoxicity. PMID- 21983807 TI - Effect of the melanocortin-3 receptor Thr6Lys and Val81Ile genetic variants on body composition and substrate oxidation in Chilean obese children. AB - Mice genetically deficient in the melanocortin-3 receptor gene are characterized by normal body weight, increased body fat, mild hypophagia, reduced locomotor activity, and increased respiratory quotient compared with wild-type mice. In humans, the 6Lys-81Ile haplotype of melanocortin-3 receptor (MC3R) gene has been associated with childhood obesity, higher body fat percentage, and reduced fat oxidation compared to non-carriers. The aim of this study was to evaluate the association between MC3R 6Lys-81Ile haplotype with body composition and substrate oxidation in response to moderate exercise in obese children. Eight Chilean obese children (aged 8-12) carriers of MC3R 6Lys-81Ile haplotype were compared with eight age-gender-matched obese non-carriers. Children were identified through a previous cross-sectional study on genetic determinants of childhood obesity (n = 229). Genotypes for MC3R Thr6Lys and Val81Ile were determined by polymerase chain reaction-restriction fragment length polymorphism. Body composition was assessed by the four-compartment model (dual-energy X-ray absorptiometry, total body water by the deuterium dilution technique, and total fat mass by air-displacement plethysmography). Substrate oxidation was assessed by indirect calorimetry in response to moderate exercise (60% VO(2 max)). Wilcoxon matched-pairs test was used to compare quantitative variables. No significant differences among carriers and non-carriers were found in anthropometrical and body composition measurements. The Carriers of the 6Lys-81Ile haplotype showed higher respiratory quotient (p = 0.06) and a significantly higher glucose oxidation (p = 0.01) compared with non-carriers after standardization for fat-free mass. Our results are consistent with a possible participation of MC3R 6Lys-81Ile variants in glucose oxidation in response to moderate exercise. PMID- 21983808 TI - Acyclic boron-containing pi-ligand complexes: eta2- and eta3-coordination modes. AB - Cyclic boron-containing pi-ligands such as boratabenzenes and borollides are well established, in particular as supporting ligands. By contrast, the chemistry of acyclic boron-containing pi-ligands has remained relatively unexplored, presumably in part due to the higher reactivity of acyclic pi-ligands relative to cyclic analogues. This perspective is focused on the synthesis, structures and reactivity of isolated transition metal complexes bearing eta(n)-coordinated (n = 2 or 3) acyclic boron-containing ligands. Both monometallic and multimetallic compounds are included, and are discussed with an emphasis on metal-ligand and intraligand bonding and parallels with hydrocarbon pi-ligand complexes. PMID- 21983809 TI - Examining the relationship between psychosocial working conditions, physical work demands, and leisure time physical activity in Canada. AB - OBJECTIVE: To examine the effects of psychosocial working conditions and physical work demands on leisure time physical activity (LTPA). METHODS: Using path analysis, direct and indirect effects of self-reported working conditions on LTPA levels were assessed in a representative sample of 4167 workers from the 2000 to 2001 Canadian National Population Health Survey. RESULTS: Higher levels of skill discretion and decision latitude were associated with higher LTPA. Physical work demands had opposite effects among men versus women, and skill discretion had a stronger effect among women than among men. Job security had a stronger effect on older workers and those without children younger than 13 years. CONCLUSIONS: The results support the influence of the work environment on LTPA and suggest that certain work conditions should be targeted in future interventions seeking to impact participation in physical activity. PMID- 21983810 TI - Stress and workplace productivity loss in the Heart of New Ulm project. AB - OBJECTIVE: The impact of stress in conjunction with lifestyle factors on workplace productivity is understudied, thus the relationship between these variables was examined. METHODS: Negative binomial regression was used to test the cross-sectional association between stress and productivity loss in a sample of 2823 adults. RESULTS: After body mass index adjustment, there was an interaction between stress and physical activity (beta +/- SE = 0.002 +/- 0.001, P = 0.033). Active participants with low stress had 2% estimated productivity loss, whereas active participants with high stress had more than 11% productivity loss. Other lifestyle factors were not significant. CONCLUSIONS: Higher stress generally predicted greater productivity loss, but this association varied. At low stress, more activity was associated with less productivity loss. At high stress, more activity was associated with more productivity loss, perhaps indicating that individuals cope by exercising more and working less. PMID- 21983814 TI - Enantioseparations 2011. PMID- 21983813 TI - Skin-specifically transgenic expression of biologically active human cytoxic T lymphocyte associated antigen4-immunoglobulin (hCTLA4Ig) in mice using lentiviral vector. AB - Xenogeneic skin, especially porcine skin, has already been used to cover large wounds in clinic practice of wound care. Our previous data showed that transgenic expression of human cytoxic T-lymphocyte associated antigen4-immunoglobulin (hCTLA4Ig) in murine skin graft remarkably prolonged its survival in xenogeneic burn wounds without extensive immunosuppression in recipients, suggesting that transgenic hCTLA4Ig expression in skin graft may be an effective and safe method to prolong its survival in xenogeneic wounds for coverage. Lentiviral transgenesis provides an extremely efficient and cost-effective method to produce transgenic animals. However, tissue-targeted transgenic expression of biologically functional protein by lentiviral transgenesis is rarely reported. In this work, a recombinant lentiviral vector (LV), named FKCW in this article, was constructed by inserting a skin-specific hCTLA4Ig expression cassette consisting of keratin 14 (K14) promoter, hCTLA4Ig coding sequence and an intronic fragment. Its efficacy for transgenesis and skin-specific expression of bio-active hCTLA4Ig protein was tested using mice as models. The LV FKCW was readily to be packaged and concentrated to high titres (1.287-6.254 * 10(9) TU/ml) by conventional lentivirus package system. Using eggs collected from only five mated females having been subjected to conventional super-ovulation treatment, 8 hCTLA4Ig transgenic founder mice were generated with the concentrated FKCW vector, and transgenic founder per injected and transferred egg was 6.3%, which was nearly 9 fold higher than that for DNA micro-injection with a similar transgene construct in our previous work. The lentiviral transgenic hCTLA4Ig exhibited strictly skin specific expression at a level comparable to or even slightly higher than that of transgenic hCTLA4Ig delivered by micro-injection in a similar cassette. Lentiviral transgenic hCTLA4Ig protein remarkably suppressed human lymphocyte proliferation in vitro to a degree comparable to that of commercially purchased purified hCTLA4Ig protein with defined activity at similar concentrations. Besides, lentiviral hCTLA4Ig transgenic mouse skin grafted into rat burn wounds exhibited remarkably extended survival compared to wild-type skin of the same strain (13.8 +/- 3.8 vs. 6.8 +/- 3.0 days), indicating that lentiviral transgenic hCTLA4Ig did inhibit immune rejection against xenogeneic skin graft in vivo. These results laid down the foundation to further efficiently generate transgenic pigs skin-specifically expressing bio-active hCTLA4Ig by lentiviral transgenesis, and provided a demonstration that transgenic animals with tissue-targeted expression of biologically functional protein can be efficiently produced using LV. PMID- 21983815 TI - Chiral analysis of amphetamines, methadone and metabolites in biological samples by electrodriven methods. AB - Amphetamines and methadone are synthetic chiral drugs with a high potential for abuse. As such, several analytical methods have been developed for their enantioseparation and analysis in biological tissues, and some of these are based on electrodriven techniques. In this review, the most important and recent of these latter methods are reviewed and their main advantages and disadvantages are discussed. Particular attention is paid to the suitability of each method for the application to the biological matrix of interest: while all methods have been successfully applied for one or more biological tissues, to reach this goal they must overcome the sensitivity problem that is common to almost all capillary electrophoretic techniques. Most methods use one or more cyclodextrin derivatives as the chiral selector, thus the separation mechanism is not particularly complicated or unusual. PMID- 21983817 TI - Synthesis, analytical characterization and initial capillary electrophoretic use in an acidic background electrolyte of a new, single-isomer chiral resolving agent: heptakis(2-O-sulfo-3-O-methyl-6-O-acetyl)-beta-cyclodextrin. AB - The sodium salt of heptakis(2-O-sulfo-3-O-methyl-6-O-acetyl)cyclomaltoheptaose (HAMS), the first single-isomer sulfated beta-CD that carries the sulfo group exclusively at the C2 position, has been synthesized. The purity of each synthetic intermediate and of the final product was determined by hydrophilic interaction (HILIC) and reversed-phase HPLC. The structural identity of each intermediate and of the final product was verified by 1-D and 2-D NMR spectroscopy and MALDI-TOF MS. HAMS was used for the capillary electrophoretic separation of the enantiomers of a set of non-ionic and weak base analytes in pH 2.5 background electrolytes. Rapid separations with satisfactory peak resolution values were obtained for most enantiomers using low concentrations of HAMS. The effective mobilities and separation selectivities were dependent on the concentration of HAMS according to the predictions of the charged resolving agent migration model. The separation selectivities observed with HAMS, heptakis(2-O methyl-3-O-acetyl-6-O-sulfo)cyclomaltoheptaose and heptakis(2-O-methyl-3,6-di-O sulfo)cyclomaltoheptaose were different for some of the analytes studied in detail. PMID- 21983816 TI - Evaluation of the interaction between sitagliptin and cyclodextrin derivatives by capillary electrophoresis and nuclear magnetic resonance spectroscopy. AB - An aqueous capillary electrophoretic method was developed for chiral analysis of the novel anti-diabetic drug, sitagliptin. The acid-base profiling of the analyte was carried out using both capillary electrophoresis and nuclear magnetic resonance pH titrations. The apparent complex stability and chiral separation properties were investigated with 30 different cyclodextrins under acidic conditions. The effect of concentration and pH of the BGE, temperature of the capillary, and the type and concentration of the chiral selector on the enantiomer resolution were thoroughly investigated. The effects of dual cyclodextrin systems on separation were also extensively studied. Complete separation of racemic sitagliptin with good resolution (R(S)=2.24) was achieved within a short time (15 min) with optimized parameters (10 degrees C, pH=4.4, 40 mM phosphate buffer) of a sulfobutylether-beta-cyclodextrin (averaged degree of substitution ~4) and native beta-cyclodextrin dual system. The averaged stoichiometry of the inclusion complex was determined using the Job plot method with both (1)H and (19)F NMR experiments and resulted in a 1:1 complex. The structure of the inclusion complex was elucidated using 2-D ROESY NMR experiments. PMID- 21983818 TI - Capillary electrophoresis method for the determination of isradipine enantiomers: stability studies and pharmaceutical formulation analysis. AB - A simple enantioselective method based on CE using CD as chiral selector was developed and validated for the determination of isradipine (IRD) enantiomers in a pharmaceutical formulation and for the determination of IRD enantiomers in degradation studies. After optimization, the best results were obtained using 15 mM borate buffer at pH 9.3 and sulfobutyl ether-beta-cyclodextrin (2.5%, w/v) as chiral selector. The applied voltage was +30 kV, and the sample injection was performed in the hydrodynamic mode. All analyses were carried out in a fused silica uncoated capillary with an id of 50 MUm and total length of 60.0 cm. Under these conditions, a complete separation between IRD enantiomers was achieved in less than 7 min. Linearity was obtained in the range 50-300 MUg/mL for both enantiomers (r>=0.9978). The RSD (%) and relative errors (%) obtained in precision and accuracy studies (intra-day and inter-day) were lower than 5%. Therefore, this method was found to be appropriate for controlling pharmaceutical formulations containing IRD enantiomers and the assay was considered to be stability indicating. The drug was subjected to oxidation, hydrolysis and photolysis. In all stress conditions the drug presented considerable degradation when compared with a fresh sample (zero time). PMID- 21983819 TI - Enantiomeric separation of FMOC-amino acids by nano-LC and CEC using a new chiral stationary phase, cellulose tris(3-chloro-4-methylphenylcarbamate). AB - A novel polysaccharide-based chiral stationary phase (CSP), cellulose tris(3 chloro-4-methylphenylcarbamate), also known as Sepapak-2 or Lux Cellulose-2, has been evaluated for the enantiomeric separation of FMOC derivatives of amino acids. After mobile-phase optimization in nano liquid chromatography (nano-LC) the column enabled the enantiomeric separation of 19 out of 23 amino acids tested, indicating the high chiral recognition power of this new CSP. Subsequently, a comparison of the driving force employed (pressure or voltage) was carried out comparing nano-LC and CEC under the same conditions. Better peak efficiencies and resolution were observed by using CEC experiments, which enabled the chiral discrimination of 20 out of 23 amino acids tested. Finally, in order to show the potential of this new CSP, the determination of the content and the enantiomeric purity of the non-protein amino acid citrulline in food supplements was performed. For that purpose, the method was optimized, evaluated and applied to different commercial samples. PMID- 21983820 TI - Enantioselectivity of monolithic silica stationary phases immobilized with different concentrations cellulose tris (3,5-dimethylphenylcarbamate), analyzed with different mobile phases in capillary electrochromatography. AB - The 3,5-dimethylphenylcarbamate derivatives of cellulose bearing 3 (triethoxysilyl)propyl residues were immobilized in a capillary format onto a monolithic silica support by intermolecular polycondensation of the triethoxysilyl groups. The resulting columns were used for chiral separations using capillary electrochromatography. The effects of the synthesizing solvent, the selector coating procedure, the chiral selector concentration onto the silica monolith and the mobile phase pH value, on the separation of enantiomers were studied. The column-to-column reproducibility and stability also were evaluated. A test set of 14 chiral substances, including acidic, neutral, bifunctional and basic compounds, was used to investigate the effects of the factors mentioned above. Twelve pairs of enantiomers showed enantioselectivity at some of the different conditions tested. The column-to-column repeatability was satisfactory, and the prepared columns were stable under the adopted analysis conditions. PMID- 21983822 TI - Enantioselective capillary electrophoresis for the assessment of CYP3A4-mediated ketamine demethylation and inhibition in vitro. AB - Enantioselective CE with sulfated cyclodextrins as chiral selectors was used to determine the CYP3A4-catalyzed N-demethylation kinetics of ketamine to norketamine and its inhibition in the presence of ketoconazole in vitro. Ketamine, a chiral phencyclidine derivative, was incubated with recombinant human CYP3A4 from a baculovirus expression system as racemic mixture and as single enantiomer. Alkaline liquid/liquid extracts of the samples were analyzed with a pH 2.5 buffer comprising 50 mM Tris and phosphoric acid together with either multiple isomer sulfated beta-cyclodextrin (10 mg/mL) or highly sulfated gamma cyclodextrin (2%, w/v). Data obtained in the absence of ketoconazole revealed that the N-demethylation occurred stereoselectively with Michaelis-Menten (incubation of racemic ketamine) and Hill (separate incubation of single enantiomers) kinetics. Data generated in the presence of ketoconazole as the inhibitor could best be fitted to a one-site competitive model and inhibition constants were calculated using the equation of Cheng and Prusoff. No stereoselective difference was observed, but inhibition constants for the incubation of racemic ketamine were found to be larger compared with those obtained with the incubation of single ketamine enantiomers. PMID- 21983821 TI - Evaluation of a methacrylate-bonded cyclodextrins as a monolithic chiral stationary phase for capillary electrochromatography (CEC)-UV and CEC coupled to mass spectrometry. AB - Glycidyl methacrylate-bonded beta-cyclodextrin (GMA-beta-CD) is synthesized as a new chiral monomer by direct chemical bonding with GMA using a fast and simple alternative procedure. Next, rigid and homogenous monolithic columns were prepared by polymerization of GMA-beta-CD monomer with ethylene dimethacrylate (EDMA), in the presence of commonly used porogens and a charged achiral monomer to form a versatile chiral monolith. This is the first report in which a preparation procedure for a methacrylate-bonded CD is introduced for chiral separations in CEC. The degree of substitution of GMA-beta-CD monomer and mobile phase parameters were optimized to achieve the highest enantioselectivity and plate number. To evaluate the GMA-beta-CD monolithic column, different classes of chiral compounds were screened. Under the optimized beta-CD monolith phase and the optimum mobile-phase conditions, 30 neutral and basic chiral compounds and two acidic compounds could be separated. The high chemical and mechanical stability, homogenous microflow and no loss of material at the interface allows for the first time the feasibility of applying this polymer-based monolithic column for CEC coupled to ESI-MS. Compared with CEC-UV, CEC-ESI-MS showed higher sensitivity and lower resolution. However, resolution greater than 1.0 can still be obtained for majority of the select tested compound in CEC-ESI-MS with at least three out of seven compound providing Rs>=1.5. The results reinforce the potential of GMA-beta-CD monolithic columns for chiral separations with high sensitivity in CEC-ESI-MS. Finally, using hexobarbital as the model chiral analyte, the monolithic column demonstrated excellent stability and reproducibility of retention time and enantioselectivity. PMID- 21983823 TI - Analysis of chiral amino acids in cerebrospinal fluid samples linked to different stages of Alzheimer disease. AB - Chiral micellar electrokinetic chromatography with laser-induced fluorescence detection (chiral-MEKC-LIF) was used to investigate D- and L-amino acid contents in cerebrospinal fluid (CSF) samples related to different Alzheimer disease (AD) stages. CSF samples were taken from (i) control subjects (S1 pool), (ii) subjects showing a mild cognitive impairment who remained stable (S2 pool), (iii) subjects showing an mild cognitive impairment that progressed to AD (S3 pool) and (iv) subjects diagnosed with AD (S4 pool). The optimized procedure only needed 10 MUL of CSF and it included sample cleaning, derivatization with FITC and chiral-MEKC LIF separation. Eighteen standard amino acids were baseline separated with efficiencies up to 703,000 plates/m, high sensitivity (LODs in the nM range) and good resolution (values ranging from 2.6 to 9.5). Using this method, L-Arg, L Leu, L-Gln, gamma-aminobutyric acid, L-Ser, D-Ser, L-Ala, Gly, L-Lys, L-Glu and L Asp were detected in all the CSF samples. S3 and S4 samples (i.e. AD subjects) showed significant lower amounts of L-Arg L-Lys, L-Glu and L-Asp compared to the non-AD S1 and S2 samples, showing in the S4 group the lowest amounts of L-Arg L Lys, L-Glu and L-Asp. Moreover, gamma-aminobutyric acid was significantly higher in AD subjects with the highest amount also found for S4. No significant differences were observed for the rest of amino acids including D-Ser. Based on the obtained chiral-MEKC-LIF data, it was possible to correctly classify all the samples into the four groups. These results demonstrate that the use of enantioselective procedures as the one developed in this work can provide some new light on the investigations of AD, including the discovery of new biomarkers related to different stages of AD. PMID- 21983826 TI - Vascular access: an historical perspective from Sir William Harvey to the 1956 Nobel prize to Andre F. Cournand, Werner Forssmann, and Dickinson W. Richards. AB - Sir William Harvey (1578-1657), who had many precursors, discovered blood circulation in 1628 after a significant number of anatomic dissection of cadavers; his studies were continued by Sir Christopher Wren and Daniel Johann Major. The first central vein catheterization was performed on a horse by Stephen Hales, an English Vicar. In 1844, a century later, the French biologist Claude Bernard attempted the first carotid artery cannulation and repeated the procedure in the jugular vein, again on a horse. He was first to report the complications now well known to be associated with this maneuver. In 1929 Werner Forssmann tried cardiac catheterization on himself, but could not investigate the procedure further since his findings were rejected and ridiculed by colleagues. His work was continued by Andre Frederic Cournand and Dickinson Woodruff Richards Jr in the United States. In 1956 the three physicians shared the Nobel Prize for Medicine for their studies on vascular and cardiac systems. The genius and the perseverance of the three physicians paved the way towards peripheral and central catheter vein placement, one of the most frequently performed maneuvers in hospitals. Its history still remains unknown to most and deserves a short description. PMID- 21983827 TI - Outcomes of arteriovenous fistulae compared with heparin-bonded and conventional grafts for hemodialysis access. AB - PURPOSE: Arteriovenous fistulae (AVF) are the preferred vascular access for hemodialysis patients. However, patients who do not have suitable veins require prosthetic arteriovenous graft (AVG) placement. We analyzed the patency and complication rates of upper extremity brachiocephalic AVF compared to brachioaxillary tapered heparin-bonded AVG and conventional AVG. METHODS: We performed a retrospective analysis of patients who underwent a permanent vascular access procedure at our tertiary referral center from 2006 to 2008. Factors presumed to affect patency and complication rates including age, body-mass index, dyslipidemia, hypertension, and diabetes were analyzed. Complication rates, re interventions, primary, primary-assisted, and cumulative patency rates were compared using logistic regression analysis. RESULTS: We performed 138 upper extremity access procedures during the study period, including 64 brachiocephalic fistulae, 21 brachioaxillary heparin-bonded, and 21 brachioaxillary conventional AVGs. Nine patients were excluded from long-term follow-up. The 1-year cumulative patency rates for AVF, heparin-bonded, and conventional AVGs were 83%, 44%, and 67%, respectively (P=.0001). On multivariate regression analysis, only use of heparin-bonded AVG affected cumulative patency. CONCLUSIONS: Although selection bias cannot be excluded in this retrospective study, heparin-bonded AVGs did not perform better than conventional AVGs. Co-morbid conditions did not affect the cumulative patency or complication rates of brachiocephalic AVF or AVG in this analysis. Larger, randomized trials are needed to validate the results of this study. PMID- 21983829 TI - Medial brachial fascial compartment syndrome related to vascular access for hemodialysis. PMID- 21983828 TI - Vascular access flow reduction for arteriovenous fistula salvage in symptomatic patients with central venous occlusion. AB - PURPOSE: Vascular access patients with central vein (CV) stenosis or occlusion may have significant symptoms. Treatment is generally by balloon angioplasty, with or without stenting. However, CV lesions may not be correctable and when treated, tend to recur. Surgical bypass of CV obstruction is a major procedure and ligation of the access may leave the patient dependent on catheter dialysis. We review a precision inflow banding procedure to limit vascular access flow and pressure for symptomatic patients with CV obstruction while preserving access functionality. MATERIALS AND METHODS: All individuals with symptomatic CV occlusive disease who underwent an autogenous vascular access inflow restriction procedure by the two senior authors were identified. All had failed attempts to correct CV lesions by angioplasty and stent placement. A precision banding procedure was used for access inflow reduction with the addition of real-time intravascular flow monitoring. RESULTS: Twenty-two patients were identified. Ages were 22-72 years (mean=43 years). Nine patients (40.9%) were women, and 8 (36.4%) obese. Mean access flow was 1640 mL/minute before banding decreased to 820 mL/minute after banding (P< .01). All patients had access salvage. Swelling resolved promptly in 20 patients and was markedly improved in two individuals. Three patients underwent aneurysm repair with simultaneous inflow banding and decreased intra-access pressure after flow restriction. Two fistulas failed at eight and 13 months. Mean follow-up was 8 months. CONCLUSIONS: The symptoms of hemodialysis vascular access patients associated with non-correctable central venous lesions resolved successfully and their access was maintained using a precision inflow banding procedure. PMID- 21983830 TI - A single center study of clinical success in radiocephalic fistula creation. AB - PURPOSE: To compare standard methods (control) with a new protocol for radiocephalic fistula (RCF) creation involving ultrasound vein mapping by the surgeon in the operating room, ligation of cephalic vein branches in the lower forearm, and use of a tourniquet for the arteriovenous anastomosis. METHODS: This is a retrospective cohort study of patients who underwent radiocephalic fistula creation between April 2008 and March 2010 in a regional vascular center. Patients were identified retrospectively by reviewing hospital operating room and office billing records. The electronic charts of all patients were reviewed. The primary endpoint was functional RCF patency at last follow-up. RESULTS: A total of 118 patients underwent arteriovenous (AV) fistula creation by 3 surgeons during the two-year study period. Of these, 59 patients underwent RCF creation, 33 of whom were managed using the new protocol. The two groups were comparable, except for age (66 in the study group vs. 60 in the control group, P=.04). Tourniquet use shortened operative time from 48 to 36 minutes (P=.04). Functional patency was 82% vs 77% (P=.64). CONCLUSION: The new protocol for RCF creation results in shorter operative times and high functional patency rates. PMID- 21983831 TI - The kinase GLK controls autoimmunity and NF-kappaB signaling by activating the kinase PKC-theta in T cells. AB - Protein kinase C-theta (PKC-theta) is required for activation of the transcription factor NF-kappaB induced by signaling via the T cell antigen receptor (TCR); however, the direct activator of PKC-theta is unknown. We report that the kinase GLK (MAP4K3) directly activated PKC-theta during TCR signaling. TCR signaling activated GLK by inducing its direct interaction with the upstream adaptor SLP-76. GLK-deficient mice had impaired immune responses and were resistant to experimental autoimmune encephalomyelitis. Consistent with that, people with systemic lupus erythematosus had considerable enhanced GLK expression and activation of PKC-theta and the kinase IKK in T cells, and the frequency of GLK-overexpressing T cells was directly correlated with disease severity. Thus, GLK is a direct activator of PKC-theta, and activation of GLK-PKC-theta-IKK could be used as new diagnostic biomarkers and therapeutic targets for systemic lupus erythematosus. PMID- 21983832 TI - The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease. AB - Leucine-rich repeat kinase 2 (LRRK2) has been identified by genome-wide association studies as being encoded by a major susceptibility gene for Crohn's disease. Here we found that LRRK2 deficiency conferred enhanced susceptibility to experimental colitis in mice. Mechanistic studies showed that LRRK2 was a potent negative regulator of the transcription factor NFAT and was a component of a complex that included the large noncoding RNA NRON (an NFAT repressor). Furthermore, the risk-associated allele encoding LRRK2 Met2397 identified by a genome-wide association study for Crohn's disease resulted in less LRRK2 protein post-translationally. Severe colitis in LRRK2-deficient mice was associated with enhanced nuclear localization of NFAT1. Thus, our study defines a new step in the control of NFAT activation that involves an immunoregulatory function of LRRK2 and has important implications for inflammatory bowel disease. PMID- 21983834 TI - Sudden death due to polyarteritis nodosa. AB - Classical polyarteritis nodosa (cPAN) refers to a rare, potentially fatal systemic transmural necrotizing vasculitis that usually affects medium-sized, and occasionally small, muscular arteries, primarily involves the kidneys, gastrointestinal tract, skin, nervous system, joints, and muscles, and is rarely, if ever, expressed in the lungs. The incidence of mortality has significantly decreased with recently developed treatment modalities, in particular antiviral medications. Sudden death due to previously undiagnosed cPAN is rarely encountered. We report a case of a young man who had been evaluated on three occasions by medical personnel in the 3 weeks prior to his death. He had complained of nonspecific symptoms of abdominal and perineal/suprapubic pain, nausea, vomiting, sensation of chilling, and constipation. The spectrum of diagnoses included "gastroenteritis," enteric infection, and prostatitis. Found agonal at home and dying despite immediate cardiopulmonary resuscitation (CPR), he underwent a medicolegal autopsy, which revealed vasculitis of various organs, including heart (myocardium and epicardium) and extramural coronary arteries, liver, spleen, kidneys, adrenal glands, stomach and bowel, omentum, gallbladder, and pancreas. His sudden death was cardiac in nature due to PAN associated clinically with hepatitis B surface antigen positivity (hepatitis B virus associated PAN [HBV-PAN]). A complete autopsy with thorough histopathological examination is necessary to diagnose this uncommon yet potentially fatal vasculitis. PMID- 21983833 TI - An IL-9 fate reporter demonstrates the induction of an innate IL-9 response in lung inflammation. AB - Interleukin 9 (IL-9) is a cytokine linked to lung inflammation, but its cellular origin and function remain unclear. Here we describe a reporter mouse strain designed to map the fate of cells that have activated IL-9. We found that during papain-induced lung inflammation, IL-9 production was largely restricted to innate lymphoid cells (ILCs). IL-9 production by ILCs depended on IL-2 from adaptive immune cells and was rapidly lost in favor of other cytokines, such as IL-13 and IL-5. Blockade of IL-9 production via neutralizing antibodies resulted in much lower expression of IL-13 and IL-5, which suggested that ILCs provide the missing link between the well-established functions of IL-9 in the regulation of type 2 helper T cell cytokines and responses. PMID- 21983835 TI - Acutely elevated cortisol in response to stressor is associated with attentional bias toward depression-related stimuli but is not associated with attentional function. AB - Cortisol induces attentional bias toward a negative stimulus and impaired attentional function. Depressed individuals have high levels of cortisol, and exhibit an attentional bias toward a depression-related stimulus and impaired processing speed and executive attention, which are components of attentional function. Therefore, the study tested the hypotheses that an acute increase in cortisol in response to a stressor is associated with attentional bias toward a depression-related stimulus and impaired processing speed and executive attention. Thirty-six participants were administered the dot-probe task for the measurement of attentional bias toward a depression-related stimulus and the Trail Making Test A and B for the measurement of processing speed and executive attention before and after a mental arithmetic task. It was revealed that attentional bias toward a depression-related stimulus following the stressor was observed only among the responders (i.e., participants with cortisol elevation in response to a stressor). On the other hand, no differences in the performance of processing speed and executive attention were noted between the responders and non-responders. The results indicate that acutely elevated cortisol is related to attentional bias, but is not related to processing speed and executive attention. The results have an implication for the etiology of depression. PMID- 21983836 TI - Comparative in silico analysis of chemotaxis system of Campylobacter fetus. AB - Chemoreceptor and chemotaxis signal transduction cascade genes of C. fetus subsp. fetus 82-40 show high level of similarity to that in C. jejuni and appears to include sixteen diverse transducer-like protein (tlp) genes that appear similar to nine of the twelve tlp genes in the C. jejuni NCTC 11168 with a percent identity ranging from 15 to 50%. Sixteen putative C. fetus 82-40 tlp genes belong to three classes: A, B, and C, as well as an aerotaxis gene, based on their predicted structure. C. fetus subsp. fetus 82-40 chemoreceptor and chemotaxis signal transduction pathway genes have close phylogenetic relationship of chemotaxis genes between Campylobacteraceae and Helicobacteraceae. PMID- 21983837 TI - A comparative small-animal PET evaluation of [11C]tariquidar, [11C]elacridar and (R)-[11C]verapamil for detection of P-glycoprotein-expressing murine breast cancer. AB - PURPOSE: One important mechanism for chemoresistance of tumours is overexpression of the adenosine triphosphate-binding cassette transporter P-glycoprotein (Pgp). Pgp reduces intracellular concentrations of chemotherapeutic drugs. The aim of this study was to compare the suitability of the radiolabelled Pgp inhibitors [(11)C]tariquidar and [(11)C]elacridar with the Pgp substrate radiotracer (R) [(11)C]verapamil for discriminating tumours expressing low and high levels of Pgp using small-animal PET imaging in a murine breast cancer model. METHODS: Murine mammary carcinoma cells (EMT6) were continuously exposed to doxorubicin to generate a Pgp-overexpressing, doxorubicin-resistant cell line (EMT6AR1.0 cells). Both cell lines were subcutaneously injected into female athymic nude mice. One week after implantation, animals underwent PET scans with [(11)C]tariquidar (n = 7), [(11)C]elacridar (n = 6) and (R)-[(11)C]verapamil (n = 7), before and after administration of unlabelled tariquidar (15 mg/kg). Pgp expression in tumour grafts was evaluated by Western blotting. RESULTS: [(11)C]Tariquidar showed significantly higher retention in Pgp-overexpressing EMT6AR1.0 compared with EMT6 tumours: the mean +/- SD areas under the time-activity curves in scan 1 from time 0 to 60 min (AUC(0-60)) were 38.8 +/- 2.2 min and 25.0 +/- 5.3 min (p = 0.016, Wilcoxon matched pairs test). [(11)C]Elacridar and (R)-[(11)C]verapamil were not able to discriminate Pgp expression in tumour models. Following administration of unlabelled tariquidar, both EMT6Ar1.0 and EMT6 tumours showed increases in uptake of [(11)C]tariquidar, [(11)C]elacridar and (R)-[(11)C]verapamil. CONCLUSION: Among the tested radiotracers, [(11)C]tariquidar performed best in discriminating tumours expressing high and low levels of Pgp. Therefore [(11)C]tariquidar merits further investigation as a PET tracer to assess Pgp expression levels in solid tumours. PMID- 21983838 TI - Radioembolisation of hepatocellular carcinoma patients using 90Y-labelled microspheres: towards a diffusion of the technique? PMID- 21983840 TI - Training young oncologists in doctor-patient relationships. AB - The importance of the doctor-patient relationship is not given adequate attention during the years of study leading to a degree in medicine. This aspect is important for all patients but especially so for cancer patients. What is the best way of training young doctors to overcome this problem? PMID- 21983842 TI - Comparison of non-mesh (Desarda) and mesh (Lichtenstein) methods for inguinal hernia repair among black African patients: a short-term double-blind RCT. AB - PURPOSE: This study compared the short-term outcomes of the non-mesh (Desarda) and mesh (Lichtenstein) methods of hernia repair among Black African patients, with regard to acute postoperative pain, day of return to normal gait, operative time and complications. METHODS: A total of 101 participants (51 in the Lichtenstein arm and 50 in the Desarda arm) were enrolled into this single centre double-blind randomised controlled trial. The outcome measures were evaluated at 1-2 h, 3, 7 and 14 days. The power of the study was set at 80%, CI at 95% and a two-sided P < 0.05 was considered statistically significant. RESULTS: There was no significant difference in the mean pain score (based on Visual Analogue Scale 0-10) between the study arms [3rd postoperative day (POD): 3.33 +/- 1.75 for Lichtenstein and 2.73 +/- 1.64 for Desarda, Effect size (CI): 0.59 (-0.088-1.272) and the scores on the 7th POD were 1.31 +/- 1.19 for Lichtenstein and 1.31 +/- 1.34 for Desarda, effect size (CI): 0.00 (-0.509-0.509)]. No difference was observed in regard to mean day of resumption of normal gait [2.44 +/- 1.62 for Lichtenstein and 2.06 +/- 1.13 for Desarda, effect size (CI): 0.08 (-0.030 0.193)]. A significant difference was recorded in regard to operative time, with the Desarda repair markedly shorter in duration [15.9 +/- 3.52 min for Lichtenstein repair and 10.02 +/- 2.93 min for Desarda's repair, effect size (CI): 5.92 (4.62-7.20), P = 0.0001]. Complication rates were similar in the two study arms. CONCLUSIONS: The results of the study showed that the effectiveness of the Desarda technique with respect to influencing the early clinical outcomes of hernia repair is similar to that of the Lichtenstein method. However, the operator in this study showed that the Desarda repair requires significantly shorter operative time. PMID- 21983843 TI - Incidence of diaphragmatic hernias following minimally invasive versus open transthoracic Ivor Lewis McKeown esophagectomy. AB - OBJECTIVES: To compare the incidence of post-operative hiatal herniation after open and minimally invasive Ivor Lewis McKeown esophagectomy for malignant disease. METHODS: All patients undergoing esophageal resection were entered into a prospectively maintained database. After Institutional Review Board approval, the database was queried to identify patients who underwent minimally invasive (MIE) and open transthoracic (TTE) Ivor Lewis McKeown esophagectomy (transthoracic three-hole) with gastric pull-up for malignant disease. The cohorts were compared for the incidence of hiatal hernia on routine CT scan for cancer surveillance. Data up to 24 months post-operatively was included. Patients undergoing trans-hiatal or hybrid procedures as well as intra-thoracic anastomosis were excluded as were patients in whom jejunum or colon was used for reconstruction. RESULTS: Between 2003 and 2009, 19 MIEs and 20 open TTEs met the inclusion criteria. There was no significant difference in age, co-morbidity, pathology or perioperative morbidity and mortality between the two groups. During routine follow-up, para-gastric hiatal hernia was noted on CT scan in 5(26%) patients following MIE at a mean of 13.8 months postoperatively, with incidence ranging from 3 to 20 months postoperatively (19, 20, 18, 3, and 9 months, respectively). Hernia contents in these patients were omentum in one case and colon in the other four cases. None of the patients undergoing TTE were noted to have herniation (P = 0.01). All hernias were asymptomatic; three were repaired electively. CONCLUSIONS: There was a significantly higher incidence of para gastric hiatal hernia after Ivor Lewis McKeown minimally invasive esophagectomy compared to similar open procedures. Additional precautions to prevent para gastric hernia should be taken during laparoscopic resection. PMID- 21983844 TI - Competence in coping with stress in adolescents from three regions of the world. AB - The ways adolescents develop and use strategies to cope with stress vary according to cultural scripts and values. This cross-sectional study tested the impact of region and gender on adolescents' stress perceptions and coping styles. A total sample of 10,941 adolescents (51.3% female) from 20 countries completed questionnaires on stress and coping behaviors in four domains (school, parents, peers, and romantic relationships). Standardized samples of n = 200 were drawn from each country, resulting in a sample of N = 4,000 adolescents (mean age 15.18, SD = 1.76, balanced gender distribution). Based on the results of discriminant analysis, the adolescents could be grouped into three world regions (Western, Eastern/Asian, and Southern). Results revealed that levels of perceived stressfulness of issues in different domains were universally similar among adolescents from all three regions. Parent- and school-related stress received the highest rankings, and peer- and romance-related stress the lowest. Differences emerged with respect to coping style, depending on region and gender. Coping styles characterized by negotiating, seeking support, and emotional outlet were used more often by adolescents from the Western region than those from the Eastern/Asian or Southern regions. Females in all regions had higher rates in the use of negotiating and seeking support than males did. Adolescents from all countries, despite regional variations, exhibited more emotional outlet in response to conflicts with parents than with peers or romantic partners. Overall, adolescents from all regions of the world demonstrated an impressive level of coping competencies, as only about one fifth of all coping responses involved the use of withdrawal and denial. The findings are discussed with respect to how the effects of globalization and changing societal expectations may have contributed to similar levels of perceived stressfulness and increased coping agency in adolescents in different parts of the world. PMID- 21983846 TI - Electrolyte disturbances in acute pyelonephritis. AB - The aim of this study was to determine whether renal unresponsiveness to aldosterone associated with hyperkalemia is present in infants with acute pyelonephritis in the absence of significant urinary tract anomalies and to describe the clinical characteristics of patients presenting an inadequate renal response to hyperkalemia. The patient cohort comprised 113 infants with acute pyelonephritis (APN), based on the criteria of a temperature >38 degrees C and significant bacteriuria. Serum and urine electrolytes, creatinine, osmolality, and renal tubular function tests were performed at diagnosis. The findings were compared to those present in 75 children who had fever without significant bacteriuria. Hyperkalemia (>5.5 mmol/L) was observed in infants with an APN diagnosis, who exhibited a lower transtubular potassium concentration gradient (TTKG) and a higher fractional sodium excretion. We defined inadequate renal response to hyperkalemia as the combination of hyperkalemia and TTKG below the normal range established for the age of the subject. Infants presenting an inadequate response to hyperkalemia were younger and associated more frequently with an APN diagnosis. This alteration could be explained by the renal interstitial inflammation present in acute pyelonephritis and the immaturity of the renal tubular responsiveness to aldosterone due to infancy in the absence of urinary tract infection or obstruction. PMID- 21983848 TI - Glucose intolerance: is it a risk factor for cardiovascular disease in children with chronic kidney disease? AB - A total of 66 children and adolescents with chronic kidney disease (CKD) (20 pre dialysis patients and 46 chronic dialysis patients) were evaluated to address the prevalence of abnormalities in glucose and insulin metabolism and their association with cardiovascular disease. Glucose intolerance was assessed using an oral glucose tolerance test; insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR). Carotid artery intima-media thickness (IMT) and left ventricular hypertrophy (LVH) were examined as early markers of cardiovascular disease. Thirty-four patients (7 pre-dialysis, 27 dialysis) exhibited an abnormal glucose tolerance; however, ten patients (7 pre-dialysis, 3 dialysis) were insulin-resistant. Height-specific standard deviation scores of carotid artery IMT were above normal in three of the pre dialysis patients (15%) and in 34 of the dialysis patients (74%). LVH was present in seven pre-dialysis (35%) and 34 dialysis patients (74%). In addition, two of the pre-dialysis patients (10%) and 18 of the dialysis patients (39%) had severe LVH. The prevalence of both increased carotid artery IMT and LVH were similar in patients with or without glucose intolerance in both groups, but severe LVH was more prevalent in pre-dialysis patients with glucose intolerance (p = 0.042). The multivariate analyses showed that neither carotid artery IMT nor LVM index was predicted by serum glucose levels or HOMA-IR. In conclusion, children with CKD are at a high risk of glucose intolerance and also have a greater risk of subclinical cardiovascular disease (CVD). However, the presence of glucose intolerance does not appear to be an independent risk factor for increased carotid artery IMT or LVH. PMID- 21983849 TI - Are patients with encephalocraniocutaneous lipomatosis at increased risk of developing low-grade gliomas? AB - INTRODUCTION: Cancer-prone genetic disorders are responsible for brain tumors in a considerable proportion of children. Additionally, rare genetic syndromes associated to cancer development may potentially disclose genetic mechanisms related to oncogenesis. METHOD: We describe two pediatric patients with encephalocraniocutaneous lipomatosis (ECCL), a very rare genetic syndrome with around 60 reported cases, which developed low-grade astrocytoma at 3 and 12 years of age. RESULTS: Patients with ECCL seem to be at risk of benign forms of osseous tumors such as ossifying fibromas, odontomas, and osteomas. CONCLUSION: The association between brain tumor and ECCL was previously reported only once, in a pediatric case of a mixed neuronal-glial histology. Whether ECCL may be a genetic condition of predisposing brain tumor in children strongly needs to be addressed. PMID- 21983850 TI - Three-year-old patient with giant MCA aneurysm treated by trapping-resection plus STA-MCA bypass. Case report. PMID- 21983851 TI - Changes in activity of non-specific esterases in cadmium treated Lymantria dispar larvae. AB - Many biochemical, physiological and histological criteria have been used as indicators of exposures and effects of the contaminants. These changes can indicate the response of an organism to a specific environmental stressor. In the present paper, the effect of the acute and chronic exposure to cadmium as well as recovery from two cadmium concentrations (10 and 30 MUgCd/g dry food) on gypsy moth (Lymantria dispar) midgut esterases was investigated. The influence of cadmium on trait plasticity was also examined. Esterases showed great sensitivity to low metal concentrations during acute and chronic treatments. Their activities during short-term exposure and after recovery significantly depended on cadmium concentrations. The esterases had greater index of plasticity during chronic treatments with 10 and 30 MUgCd/dry food. Five esterase isoforms between 64 and 250 kDa were detected. Isoforms of esterases exposed to any of the two cadmium effects differed among several egg-masses. Isozymes were distinguished in one egg mass during different cadmium treatments. We conclude that these enzymes could be considered potential and sensitive non-selective biomarkers for the presence of cadmium in food. PMID- 21983852 TI - A new conformer of indium germanate InGe3O7.5(en): conformational polymorphism in germanate family. AB - A new conformer of indium germanate InGe(3)O(7.5)(en) (denoted as delta-type), constructed with the flexible unit of In(2)Ge(6)O(15)N(2) was successfully prepared through a solvothermal method. The crystal data for the delta-type InGe(3)O(7.5)(en) are listed as follows: triclinic, space group P-1 (No.2), a = 7.826(4) A, b = 8.287(3) A, c = 9.224(4) A, alpha = 71.887(17) degrees , beta = 85.343(18) degrees , gamma = 63.734(12) degrees , V = 508.64 A(3), Z = 2. Four relevant conformers of indium germanate are compared with each other. The conformational polymorphism in the germanate family is reported for the first time. PMID- 21983853 TI - Improved measures of racial mixing among men who have sex with men using Newman's assortativity coefficient. AB - OBJECTIVE: To measure sexual mixing among racial groups of men who have sex with men (MSM). METHODS: The authors explore its potential impacts, making two methodological advancements over previous work. First, the authors pioneer the use of Newman's assortativity coefficient to characterise mixing among MSM. Second, the authors examine mixing at the level of primary ties and at the level of secondary ties. RESULTS: Results from the 1142-participant sample suggest that MSM are highly assortative by all races at the secondary level. CONCLUSIONS: Networks of MSM may be more tightly contracted around racial groupings than previously supposed. These groupings may lead to increased HIV transmission in certain racial groups. PMID- 21983854 TI - Prevalence and correlates of major depressive disorder in breast cancer survivors in Shanghai, China. AB - OBJECTIVE: Our objective is to measure the prevalence and correlates of major depressive disorder (MDD) among Chinese breast cancer patients after surgery, which is essential for analyzing the service needs and allocating mental health resources. METHODS: A total of 505 patients were randomly recruited from 1580 post-surgery breast cancer outpatients from one tertiary hospital in Shanghai, and the Mini International Neuropsychiatric Interview was used to assess 1-month prevalence of MDD according to the Diagnostic and Statistical Manual Fourth Edition (DSM-IV) in a two-phase design. RESULTS: The adjusted 1-month prevalence of MDD was 20.59% (95% CI 17.06-23.82). The risk for depression within the first year was two times as higher as that in more than 1 year. Patients within 1 year after surgery, with lower income, disrupted marriage or being single, recurrent breast cancer and psychiatric history were more likely to have MDD. There was no significant association between depression and disease stage, type of surgery, receptor status and cancer treatment. CONCLUSIONS: Depression is quite common in Chinese breast cancer patients and survivors. A more sensitive and responsive mental health service is recommended for this population. PMID- 21983855 TI - Mouse atlas registration with non-tomographic imaging modalities-a pilot study based on simulation. AB - PURPOSE: This study investigates methodologies for the estimation of small animal anatomy from non-tomographic modalities, such as planar X-ray projections, optical cameras, and surface scanners. The key goal is to register a digital mouse atlas to a combination of non-tomographic modalities, in order to provide organ-level anatomical references of small animals in 3D. PROCEDURES: A 2D/3D registration method was developed to register the 3D atlas to the combination of non-tomographic imaging modalities. Eleven combinations of three non-tomographic imaging modalities were simulated, and the registration accuracy of each combination was evaluated. RESULTS: Comparing the 11 combinations, the top-view X ray projection combined with the side-view optical camera yielded the best overall registration accuracy of all organs. The use of a surface scanner improved the registration accuracy of skin, spleen, and kidneys. CONCLUSIONS: The methodologies and evaluation presented in this study should provide helpful information for designing preclinical atlas-based anatomical data acquisition systems. PMID- 21983856 TI - Epigenetic suppression of GAD65 expression mediates persistent pain. AB - Chronic pain is a common neurological disease involving lasting, multifaceted maladaptations ranging from gene modulation to synaptic dysfunction and emotional disorders. Sustained pathological stimuli in many diseases alter the output activities of certain genes through epigenetic modifications, but it is unclear how epigenetic mechanisms operate in the development of chronic pain. We show here that in the rat brainstem nucleus raphe magnus, which is important for central mechanisms of chronic pain, persistent inflammatory and neuropathic pain epigenetically suppresses Gad2 (encoding glutamic acid decarboxylase 65 (GAD65)) transcription through histone deacetylase (HDAC)-mediated histone hypoacetylation, resulting in impaired gamma-aminobutyric acid (GABA) synaptic inhibition. Gad2 knockout mice showed sensitized pain behavior and impaired GABA synaptic function in their brainstem neurons. In wild-type but not Gad2 knockout mice, HDAC inhibitors strongly increased GAD65 activity, restored GABA synaptic function and relieved sensitized pain behavior. These findings suggest GAD65 and HDACs as potential therapeutic targets in an epigenetic approach to the treatment of chronic pain. PMID- 21983857 TI - A crucial requirement for Hedgehog signaling in small cell lung cancer. AB - Small-cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer for which there is no effective treatment. Using a mouse model in which deletion of Rb1 and Trp53 in the lung epithelium of adult mice induces SCLC, we found that the Hedgehog signaling pathway is activated in SCLC cells independently of the lung microenvironment. Constitutive activation of the Hedgehog signaling molecule Smoothened (Smo) promoted the clonogenicity of human SCLC in vitro and the initiation and progression of mouse SCLC in vivo. Reciprocally, deletion of Smo in Rb1 and Trp53-mutant lung epithelial cells strongly suppressed SCLC initiation and progression in mice. Furthermore, pharmacological blockade of Hedgehog signaling inhibited the growth of mouse and human SCLC, most notably following chemotherapy. These findings show a crucial cell-intrinsic role for Hedgehog signaling in the development and maintenance of SCLC and identify Hedgehog pathway inhibition as a therapeutic strategy to slow the progression of disease and delay cancer recurrence in individuals with SCLC. PMID- 21983858 TI - Cocaine-induced kidney toxicity: an in vitro study using primary cultured human proximal tubular epithelial cells. AB - Renal failure resulting from cocaine abuse has been well documented, although the underlying mechanisms remain to be investigated. In the present study, primary cultured human proximal tubular epithelial cells (HPTECs) of the kidney were used to investigate its ability to metabolize cocaine, as well as the cytotoxicity induced by cocaine and its metabolites benzoylecgonine (BE), ecgonine methyl ester (EME) and norcocaine (NCOC). Gas chromatography/ion trap-mass spectrometry (GC/IT-MS) analysis of HPTECs exposed to cocaine (1 mM) for 72 h confirmed its metabolism into EME and NCOC, but not BE. EME levels increased along the exposure time to cocaine, while NCOC concentration diminished after reaching a maximum at 6 h, indicating a possible secondary metabolism for this metabolite. Cocaine promoted a concentration-dependent loss of cell viability, whereas BE and EME were found to be non-toxic to HPTECs at the tested conditions. In contrast, NCOC revealed to have higher intrinsic nephrotoxicity than the parent compound. Moreover, cocaine-induced cell death was partially reversed in the presence of ketoconazole (KTZ), a potent CYP3A inhibitor, supporting the hypothesis that NCOC may play a role in cocaine-induced nephrotoxicity. Cocaine-induced cytotoxicity was found to involve intracellular glutathione depletion at low concentrations and to induce mitochondrial damage at higher concentrations. Under the present experimental conditions, HPTECs death pathway followed an apoptotic pattern, which was evident for concentrations as low as 0.1 mM. PMID- 21983859 TI - Leptomeningeal carcinomatosis from ovarian cancer. AB - Ovarian cancer is the most common cause of mortality among women with gynecologic malignancies and the fifth leading cause of death in all women. It usually spreads locally; hematogenous dissemination is rare, most often involving the liver and lungs. Cerebral metastases are reported in less than 2% of cases and tend to localize to the parenchyma, usually in the cerebrum. Leptomeningeal involvement is exceptionally rare. We report a case of a woman with metastatic ovarian cancer who developed leptomeningeal carcinomatosis while receiving systemic chemotherapy. We also provide an extensive review of the existing literature on neoplastic meningitis from ovarian cancer. PMID- 21983860 TI - Urban and non-urban disparities in the use of post-mastectomy radiation for breast cancer. AB - Post-mastectomy radiation therapy (PMRT) is indicated for local-regionally advanced breast cancer (LABC). We hypothesized that candidates for PMRT from non urban areas would receive lower rates of RT than urban patients and would have poorer overall survival (OS) and disease-specific survival (DSS). We used the Surveillance, Epidemiology, and End Results database to identify patients diagnosed with LABC and treated with mastectomy in Sacramento and its surrounding 13 counties between 2000 and 2006. All patients were eligible to receive RT according to established guidelines, with tumors >5 cm size, >= 4 metastatic lymph nodes, or both. According to a United States Department of Agriculture scale, we designated counties as urban or non-urban and used multivariate logistic regression and Cox proportional hazards models to predict the use of RT, overall survival (OS), and disease-specific survival (DSS). Density of radiation oncologists in non-urban and urban counties was determined using the American Medical Association database in relation to census-derived populations of the respective counties. Entry criteria were met by 1,507 patients. Most (56.5%) were from urban counties; only 61% received RT. There was no radiation oncologist listed for 8/10 non-urban counties and 2/4 urban counties. Each radiation oncologist served 88,804 people in non-urban counties and 68,624 residents in urban counties. On multivariate analysis, non-urban patients (OR 0.56, CI 0.44 0.72) and increasing age were the only factors predicting a decreased likelihood of receiving RT (OR 0.97, CI 0.96-0.98). Patients not receiving PMRT experienced poorer OS (HR 1.77, CI 1.39-2.25; P < 0.001) and DSS (HR 1.62, CI 1.23-2.15; P = 0.001); however, non-urban status did not predict OS or DSS. Non-urban residents with LABC are less likely to receive indicated PMRT. This discrepancy may be due to limited RT access in non-urban areas. The lack of poorer OS and DSS due to this disparity requires further study. PMID- 21983861 TI - Genetic alterations of the WWOX gene in breast cancer. AB - FRA3B and FRA16D are the most sensitive common chromosomal fragile site loci in the human genome and two tumor suppressor genes FHIT (Fragile Histidine Triad) and WWOX (WW domain-containing oxidoreductase gene) map to this sites. The WWOX gene is composed of 9 exons and encodes a 46-kD protein that contains 414 amino acids. Loss of heterozygosity, homozygous deletions, and chromosomal translocations affecting WWOX has been reported in several types of cancer, including ovarian, esophageal, lung and stomach carcinoma, and multiple myeloma. The aim of this study was to determine the role of WWOX as a tumor suppressor gene in patients with breast cancer. Tumor and adjacent non-cancerous tissue samples were obtained from 81 patients with breast cancer. DNA was isolated from all tissue samples, and all exons and flanking intronic sequences of the WWOX gene were analyzed by PCR amplification and direct sequencing. We detected 14 different alterations in the coding sequence and one base substitution at the intron 6 splice site (+1 G-A). In addition to exonic and splice-site alterations, we detected 23 different alterations in the non-coding region of the gene. All coding region mutations identified in this study were in the exons between 4 and 9. We did not observe any alterations in exons 1-3. We conclude that mutations in critical region of the WWOX gene are frequent and may have an important role in breast carcinogenesis. PMID- 21983862 TI - Coexisting ductal carcinoma in situ independently predicts lower tumor aggressiveness in node-positive luminal breast cancer. AB - Primary breast invasive ductal carcinoma coexisting with ductal carcinoma in situ (IDC-DCIS) is characterized by lower proliferation rate and metastatic propensity than size-matched pure IDC. IDC-DCIS is also more often ER-positive, PR-positive and/or HER2-positive. This analysis aims to clarify whether the presence of coexisting DCIS in IDC affects tumor aggressiveness in various biological subtypes of breast cancer, respectively. Tumor data obtained from 1,355 consecutive female patients undergoing upfront surgery for primary breast cancer were analyzed retrospectively; 196 patients with pure DCIS were excluded. Based on evidence that immunohistochemistry (IHC) provides a reasonable approximation of molecular phenotypes, the tumor samples were divided into 4 groups: (1) luminal A (ER and/or PR-positive, HER2-negative, Ki67 <= 12), (2) luminal B (ER and/or PR-positive, HER2-negative, Ki67 > 12), (3) HER2 (HER2-positive) and (4) basal-like (triple-negative) disease. Ki67 expression and nodal involvement of IDC with or without DCIS in these groups were compared. The number of patients with luminal A, luminal B, HER2 and basal-like breast cancer were 396, 265, 258 and 117, respectively. Ki-67 was lower in IDC-DCIS than in size-adjusted pure IDC of both luminal A and luminal B subtypes (P = 0.15 and <0.005, respectively). In HER2 or basal-like tumors, there were no significant difference between pure IDC and IDC-DCIS. The presence of coexisting DCIS in IDC predicts lower biological aggressiveness in luminal cancers but not in the conventionally more aggressive HER2-positive and triple-negative subtypes. PMID- 21983863 TI - Motorcycles and breast cancer: the influence of peer support and challenge on distress and posttraumatic growth. AB - PURPOSE: Peer support programs based on exercise or challenge activities may have potential to improve well-being for women diagnosed with breast cancer. The current study investigated the role of social comparison and social identity based on group membership on posttraumatic growth (PTG) and distress. METHODS: Fifty-one women diagnosed with breast cancer who participated in a 1,000 mi group motorcycle ride completed pre- and post-ride surveys. Participants had a mean age of 49.82 years (SD = 7.04) and their average time since diagnosis was 6.39 years (SD = 3.89). RESULTS: Cancer-related distress significantly decreased after the ride. PTG did not significantly differ after the ride, which may have been a result of a ceiling effect on this measure. Hierarchical regression analyses showed that pre-ride PTG (p < 0.01) and upward social comparison during the ride (p < 0.05) were related to post-ride PTG. Pre-ride distress was the only variable to remain significantly related to post-ride distress (p < 0.01). CONCLUSIONS: The results of the current study highlight the potential for challenge-based activities to provide a positive peer support environment for women diagnosed with breast cancer. Identifying factors that promote personal growth and reduce cancer-related distress allow us to create a model for the delivery of these challenge-based peer support activities. PMID- 21983864 TI - Neurological pictures in paediatric Chiari I malformation. AB - The clinical features of Chiari I Malformation (CIM) may be related to the compression of dural and/or neural structures at the craniocervical junction or to the associated syringomyelia. Additionally, patients may exhibit symptoms and signs of associated disorders. CIM is a heterogeneous and multifactorial disorder including congenital and acquired forms; it can also be found as an isolated malformation or in association with many clinical conditions. We analyse the clinical features in a series of 65 children with CIM, focusing on the high frequency of associated clinical disorders. We emphasise the importance of a careful clinical and neurological assessment for a proper diagnosis and a correct management of these patients. PMID- 21983865 TI - Can Chiari malformation negatively affect higher mental functioning in developmental age? AB - Numerous studies on adults have confirmed that the cerebellum has a role in processing higher brain functions, and evidence of this role has emerged more recently in developmental age as well. Various types of congenital lesion are associated with neuropsychological impairments and behavioral changes that can sometimes even give rise to a picture of autism. Acquired cerebellar lesions (especially tumors and stroke) in children of normal intelligence have enabled different neuropsychological profiles to be identified, depending on the cerebellar site involved. In Chiari malformation, the cerebellar structures are squeezed and crowded inside the posterior fossa and along the time this could generate various kinds of cognitive and behavioral disorders. Currently available data remain inconclusive, however, and prospective longitudinal studies on sizable series will be needed to ascertain whether and to what degree Chiari malformations may negatively affect mental functioning in developmental age. PMID- 21983866 TI - Loco-regional treatments in first-diagnosis glioblastoma: literature review on association between Stupp protocol and Gliadel. AB - Loco-regional chemotherapy with carmustine wafers (Gliadel) positioned at surgery and followed by radiotherapy has been shown to prolong survival in first diagnosis glioblastoma, as well as concomitant radiochemotherapy with temozolomide. The combination of Gliadel with the Stupp protocol has mostly been investigated in retrospective studies. objective of this study was to review the literature of efficacy and toxicities in patients with first-diagnosis glioblastoma treated with surgery, Gliadel, radiotherapy and temozolomide chemotherapy. The data in the literature regarding the combined use of Gliadel with chemotherapy, concomitant with radiotherapy and adjuvant temozolomide for glioblastoma was analyzed and compared. The results on survival and toxicity are summarized. The combination of Gliadel and radiotherapy with temozolomide is well tolerated and may increase survival without a substantial increase in major toxicity. However, only prospective comparative studies will be able to address the issue of true advantage in survival with this combination. PMID- 21983867 TI - Prefibrillar aggregates of yeast prion Sup35NM and its variant are toxic to mammalian cells. AB - The deposition of proteins as insoluble amyloid aggregates is a characteristic feature of more than 20 degenerative conditions. A growing body of evidence indicates that the oligomeric species formed by proteins, but not the mature fibrils, are inherently toxic and are associated with clinical diseases. The N terminal and middle region of Sup35 (Sup35NM), a yeast prion, can assemble into oligomers and fibrils. Here we analyze the cytotoxicity of different aggregates of Sup35NM and its variant, the proteins that is not associated with clinical disease. Our results showed that prefibrillar aggregates generated from Sup35NM and its variant Sup35NM-1 were toxic to cultured mammalian cells. In addition, the activation of caspase-3, 8, and 9 were detected, suggesting that apoptosis was involved in the observed cytotoxicity. Our findings provide evidence for the underlying mechanism of amyloid aggregate-induced cytotoxicity and suggest that it may arise from common structural features of the aggregates rather than from primary amino acid sequences. PMID- 21983868 TI - Direct regulation of interleukin-6 expression by Notch signaling in macrophages. AB - Interleukin-6 (IL-6) is a pleiotropic, pro-inflammatory cytokine produced by various types of cells, including macrophages. Within the IL-6 gene promoter region, the signature binding motif of CBF1/Su(H)/Lag-1 (CSL), a key DNA-binding protein in the Notch signaling pathway, was identified and found to overlap with a consensus nuclear factor (NF)-kappaB-binding site. Notch signaling is highly conserved and is involved in the regulation of biological functions in immune cells. In this study, we investigated the role of Notch signaling in the regulation of the IL-6 transcript in murine macrophages. The upregulation of Notch1 protein levels and the appearance of cleaved Notch1 (Val1744) correlated well with the increased IL-6 mRNA expression levels in murine primary bone marrow derived macrophages (BMMphi) after activation by lipopolysaccharide (LPS) together with interferon-gamma (IFN-gamma). Treatment of BMMphi with the gamma secretase inhibitor IL-CHO to suppress the transduction of Notch signaling resulted in a partial decrease in the level of IL-6 mRNA and the amount of IL-6 protein produced. In contrast, the overexpression of a constitutively activated intracellular Notch1 protein (N(IC)) in the RAW264.7 macrophage-like cell line resulted in significantly higher IL-6 transcript expression levels than in cells transfected with the empty vector control. The NF-kappaB inhibitor completely abrogated IL-6 mRNA expression induced by the overexpression of N(IC). Chromatin immunoprecipitation (ChIP) using an anti-Notch1 antibody demonstrated that Notch1 is associated with the IL-6 promoter in RAW264.7 cells activated by LPS/IFN-gamma but not in unstimulated cells. Taken together, these results strongly suggest that Notch1 positively regulates IL-6 expression via NF-kappaB in activated macrophages. PMID- 21983869 TI - Impairment of non-muscle myosin IIA in human CD4+ T cells contributes to functional deficits in the elderly. AB - Physiological aging imposes significant alterations in the repertoire of T cells and all associated functions. Although several studies have reported defects upon antigen-induced activation of T cells during aging, the molecular mechanisms that control T-cell receptor (TCR) downmodulation remain to be fully defined. While previous studies have assessed the role of F-actin in regulating activation induced TCR internalization, few have delineated the roles of motor proteins, such as non-muscle myosin IIA (NMMIIA). In this study, we describe a series of experiments supporting the hypothesis that effective TCR downmodulation requires not only efficient reorganization of the actin cytoskeleton, but also functional NMMIIA. For the first time, we show that CD4(+) T cells from elderly human donors have dysfunctional NMMIIA that contributes to delaying activation-induced TCR internalization and impairing calcium mobilization. Additionally, our results demonstrate that chemical inhibition of NMMIIA in CD4(+) T cells from young donors also results in complete abrogation of TCR internalization, strongly supporting the fundamental role of NMMIIA in modulating this event. Recent observations that the generation of an efficient T-cell response requires migration prompted us to investigate whether NMMIIA also plays a regulatory role in CD4(+) T-cell migration. We show that chemical inhibition of NMMIIA downmodulates chemotactic migration in CD4(+) T cells from both young and elderly donors. Together, these data demonstrate a significant contribution of dysfunctional NMMIIA to TCR-mediated functional defects during aging. PMID- 21983870 TI - Alterations of peripheral CD4+CD25+Foxp3+ T regulatory cells in mice with STZ induced diabetes. AB - Complications arising from abnormal immune responses are the major causes of mortality and morbidity in diabetic patients. CD4+CD25+T regulatory cells (Tregs) play pivotal roles in controlling immune homeostasis, immunity and tolerance. The effect of hyperglycemia on CD4+CD25+Tregs has not yet been addressed. Here we used streptozotocin (STZ)-induced diabetic mice to study the effects of long-term hyperglycemia on CD4+CD25+Tregs in vivo. Four months after the onset of diabetes, the frequency of CD4+CD25+Foxp3+ T regulatory cells was significantly elevated in the spleen, peripheral blood lymphocytes (PBLs), peripheral lymph nodes (pLNs) and mesenteric LNs (mLNs). CD4+CD25+Tregs obtained from mice with diabetes displayed defective immunosuppressive functions and an activated/memory phenotype. Insulin administration rescued these changes in the CD4+CD25+ Tregs of diabetic mice. The percentage of thymic CD4+CD25+ naturally occurring Tregs (nTregs) and peripheral CD4+Helios+Foxp3+ nTregs were markedly enhanced in diabetic mice, indicating that thymic output contributed to the increased frequency of peripheral CD4+CD25+Tregs in diabetic mice. In an in vitro assay in which Tregs were induced from CD4+CD25- T cells by transforming growth factor (TGF)-beta, high glucose enhanced the efficiency of CD4+CD25+Foxp3+ inducible Tregs (iTregs) induction. In addition, CD4+CD25- T cells from diabetic mice were more susceptible to CD4+CD25+Foxp3+ iTreg differentiation than those cells from control mice. These data, together with the enhanced frequency of CD4+Helios Foxp3+ iTregs in the periphery of mice with diabetes, indicate that enhanced CD4+CD25+Foxp3+ iTreg induction also contributes to a peripheral increase iCD4+CD25+Tregs in diabetic mice. Our data show that hyperglycemia may alter the frequency of CD4+CD25+Foxp3+ Tregs in mice, which may result in late-state immune dysfunction in patients with diabetes. PMID- 21983871 TI - The efficacy of miRNA122, a novel therapeutic target, for predicting the progression of hepatocellular carcinoma (HCC). PMID- 21983872 TI - Highly selective and sensitive chromo-fluorogenic detection of the Tetryl explosive using functional silica nanoparticles. AB - Silica nanoparticles containing polyamines and thiol groups have been used as probes for the selective detection of Tetryl. PMID- 21983873 TI - The stability of perceived pubertal timing across adolescence. AB - It is unknown whether perceived pubertal timing changes as puberty progresses or whether it is an important component of adolescent identity formation that is fixed early in pubertal development. The purpose of this study is to examine the stability of perceived pubertal timing among a school-based sample of rural adolescents aged 11-17 (N=6,425; 50% female; 53% White). Two measures of pubertal timing were used, stage-normative, based on the Pubertal Development Scale, a self-report scale of secondary sexual characteristics, and peer-normative, a one item measure of perceived pubertal timing. Two longitudinal methods were used: one-way random effects ANOVA models and latent class analysis. When calculating intraclass correlation coefficients using the one-way random effects ANOVA models, which is based on the average reliability from one time point to the next, both measures had similar, but poor, stability. In contrast, latent class analysis, which looks at the longitudinal response pattern of each individual and treats deviation from that pattern as measurement error, showed three stable and distinct response patterns for both measures: always early, always on-time, and always late. Study results suggest instability in perceived pubertal timing from one age to the next, but this instability is likely due to measurement error. Thus, it may be necessary to take into account the longitudinal pattern of perceived pubertal timing across adolescence rather than measuring perceived pubertal timing at one point in time. PMID- 21983876 TI - Mature cystic teratoma of the pancreas. AB - The pancreatic teratoma is a congenital tumor which results from abnormal embryonic development of totipotent cells. The preoperative diagnosis is challenging. We report, to our knowledge, the 26th case in a 64-year-old man in whom the diagnosis was made preoperatively on imaging. PMID- 21983875 TI - Akt/GSK-3beta/eNOS phosphorylation arbitrates safranal-induced myocardial protection against ischemia-reperfusion injury in rats. AB - PURPOSE: Traditional medicine has been appropriately identified as the most productive soil for the cultivation and harvesting of modern medicines. Herein, we postulate that safranal, an active constituent of Crocus sativus, owing to its strong antioxidant and anti-apoptotic potential, could be a valuable molecule in alleviating myocardial ischemia-reperfusion (IR) injury. METHODS: To evaluate this hypothesis, safranal (0.1-0.5 mL/kg/day, i.p.) or saline were administered to rats for 14 days, and on 15th day, one-stage ligation of left anterior descending coronary artery for 45 min was performed, followed by 60 min reperfusion. RESULTS: We concluded that safranal not only significantly decreased infarct size, but also improved left ventricular functions and the overall hemodynamic status of the myocardium. Interestingly, safranal enhanced phosphorylation of Akt/GSK-3beta/eNOS and suppressed IKK-beta/NF-kappaB protein expressions in IR-challenged myocardium. Our findings also imply that safranal exhibits strong anti-apoptotic potential, as evidenced by upregulated Bcl-2 expression and downregulated Bax and caspase3 expression with decreased TUNEL positivity. Moreover, safranal dose-dependently normalized myocardial antioxidant and nitrotyrosine levels, cardiac injury markers (LDH and CK-MB), and decreased TNF-alpha level in IR-insulted myocardium. Histopathological and ultrastructural findings correlated with the functional and biochemical outcomes showing preserved myocardial architecture and decreased inflammatory cells and edema. CONCLUSIONS: Taken together, these results provide convincing evidence of safranal as an invaluable molecule in myocardial IR setting probably due to its fortified antioxidant and anti-apoptotic potential. PMID- 21983877 TI - Chemical control of the red palm mite, Raoiella indica (Acari: Tenuipalpidae) in banana and coconut. AB - The red palm mite (RPM), Raoiella indica Hirst, is a predominant pest of coconuts, date palms and other palm species, as well as a major pest of bananas (Musa spp.) in different parts of the world. Recently, RPM dispersed throughout the Caribbean islands and has reached both the North and South American continents. The RPM introductions have caused severe damage to palm species, and bananas and plantains in the Caribbean region. The work presented herein is the result of several acaricide trials conducted in Puerto Rico and Florida on palms and bananas in order to provide chemical control alternatives to minimize the impact of this pest. Spiromesifen, dicofol and acequinocyl were effective in reducing the population of R. indica in coconut in Puerto Rico. Spray treatments with etoxanole, abamectin, pyridaben, milbemectin and sulfur showed mite control in Florida. In addition, the acaricides acequinocyl and spiromesifen were able to reduce the population of R. indica in banana trials. PMID- 21983878 TI - Plant architecture and prey distribution influence foraging behavior of the predatory mite Phytoseiulus persimilis (Acari: Phytoseiidae). AB - The arrangement, number, and size of plant parts may influence predator foraging behavior, either directly, by altering the rate or pattern of predator movement, or, indirectly, by affecting the distribution and abundance of prey. We report on the effects of both plant architecture and prey distribution on foraging by the predatory mite, Phytoseiulus persimilis Athias-Henriot (Acari: Phytoseiidae), on cucumber (Cucumis sativus L.). Plants differed in leaf number (2- or 6-leafed), and there were associated differences in leaf size, plant height, and relative proportions of plant parts; but all had the same total surface area. The prey, the twospotted spider mite Tetranychus urticae Koch (Acari: Tetranychidae), were distributed either on the basal leaf or on all leaves. The effect of plant architecture on predator foraging behavior varied depending on prey distribution. The dimensions of individual plant parts affected time allocated to moving and feeding, but they did not appear to influence the frequency with which predators moved among different plant parts. Overall, P. persimilis moved less, and fed upon prey longer, on 6-leafed plants with prey on all leaves than on plants representing other treatment combinations. Our findings suggest that both plant architecture and pattern of prey distribution should be considered, along with other factors such as herbivore-induced plant volatiles, in augmentative biological control programs. PMID- 21983881 TI - Halogenation of (phosphine chalcogenide)gold(I) halides; some unexpected products. AB - The monoselenide of 1,8-bis(diphenylphosphino)naphthalene reacts with (tht)AuCl to give the gold(III) system [(dppnAuSe)(2)](2+) 2Cl(-) (1); bromination of the bromogold(I) complex of the 1,2-bis(diphenylphosphino)methane monosulfide ligand furnishes the tribromide salt (2a) of a gold(III) cation [LAuBr(2)](+); bromination of the bromogold(I) complex of the 1,2-bis(diphenylphosphino)benzene monosulfide ligand leads to a mixed bromide/tetrabromoaurate salt (3) of a heterocyclic dication involving a [-PPh(2)-S-PPh(2)-](2+) moiety; analogous reactions of triphenylphosphine sulfide and selenide complexes lead to tetrabromoaurate salts (4a and 4b) of the (bromochalcogeno)phosphonium cations Ph(3)PEBr(+). PMID- 21983879 TI - Tipifarnib-mediated suppression of T-bet-dependent signaling pathways. AB - Large granular lymphocyte (LGL) leukemia is a chronic lymphoproliferative disease in which T-bet [T-box transcription factor 21 gene (tbx21)] overexpression may play a pathogenic role. T-bet orchestrates the differentiation of mature peripheral T-cells into interferon-gamma (IFN-gamma) and tumor necrosis factor alpha producing CD4+ T-helper type I (Th1) and CD8+ T cytotoxic cells that are necessary for antiviral responses. When IL-12 is produced by antigen-presenting cells, T-bet expression is induced, causing direct stimulation of ifng gene transcription while simultaneously acting as a transcriptional repressor of the IL4 gene, which then leads to Th1 dominance and T-helper type 2 differentiation blockade. Additionally, T-bet has been shown to regulate histone acetylation of the ifng promoter and enhancer to loosen condensed DNA, creating greater accessibility for other transcription factor binding, which further amplifies IFNgamma production. We found that treatment with a farnesyltransferase inhibitor tipifarnib reduced Th1 cytokines in LGL leukemia patient T-cells and blocked T bet protein expression and IL-12 responsiveness in T-cells from healthy donors. The mechanism of suppression was based on modulation of histone acetylation of the ifng gene, which culminated in Th1 blockade. PMID- 21983882 TI - Can interfaith research partnerships develop new paradigms for condom use and HIV prevention? The implementation of conceptual events in Malawi results in a 'spiritualised condom'. AB - OBJECTIVES: The aim of this intervention research study was to engage senior leaders of faith-based organisations (FBOs) in Malawi in a participatory process to construct an interfaith theology of HIV/AIDS. This process was designed to enhance the capacity of faith leaders to respond more effectively to the HIV/AIDS pandemic. METHODS: An evidence-driven combination of ethnographic and participatory action research methodologies was utilised. Conceptual events innovative participatory action research processes-were held over the 4-year project and brought together health service providers, policy makers and a non governmental organisation in partnership with FBOs and grassroots faith-based communities. RESULTS: Through facilitated dialogue, an interfaith theology of HIV/AIDS emerged, resulting in the proposition that a 'spiritualised condom' endorses a 'theology of protecting life'. This proposition was based on the following convictions: (1) life is sacred and to be protected, (2) to kill or murder is a 'greater sin' than the 'lesser sin of infidelity', (3) protection of the innocent is a moral and religious requirement, (4) condoms have the potential to prevent the death of an innocent person and (5) condoms need to be encouraged, even in the context of marriage. CONCLUSIONS: Clinicians, non-governmental organisations, health service providers and policy makers, assisted by health social scientists, can successfully partner with FBOs and their leaders to (1) modify and transform faith-based understandings of HIV risk and (2) bring about attitudinal and behaviour changes that help to address the challenges associated with HIV/AIDS. PMID- 21983883 TI - Evaluating the respiratory bioaccessibility of nickel in soil through the use of a simulated lung fluid. AB - Simulated lung fluids are solutions designed to mimic the composition of human interstitial lung fluid as closely as possible. Analysis of mineral dusts using such solutions has been used to evaluate the respiratory bioaccessibility of various elements for which solubility in the lungs is a primary determinant of reactivity. The objective of this study was to employ simulated lung fluid analysis to investigate the respiratory bioaccessibility of nickel in soils. Current occupational guidelines in Australia regulate nickel compounds in terms of water solubility, though this may not be an accurate estimation of the total nickel that will dissociate in the lungs. Surface soils were collected from the city of Kalgoorlie in Western Australia, the site of an operational nickel smelter and metal mining activities. The fraction of the samples less than 10 MUm was extracted from the soil, and it was this sub-10-MUm fraction that was found to hold most of the total nickel present in the soil. The fine fraction was analyzed using a simulated lung fluid (modified Gamble's solution) to isolate the nickel phases soluble in the lungs. In addition, a sequential extraction was employed to compare the bioaccessible fraction to those dissolved from different binding forms in the soil. In all samples, the simulated lung fluid extracted more nickel than the two weakest leaches of the sequential extraction combined, providing a more representative nickel bioaccessibility value than the current water leach method. PMID- 21983884 TI - Overexpression of a disintegrin and metalloprotease 8 in human gliomas is implicated in tumor progression and prognosis. AB - A disintegrin and metalloprotease 8 (ADAM8) has been shown to be expressed in various cancer types, and its expression was associated with advanced progression of several tumors. However, little is known about ADAM8 in human gliomas. Therefore, we here evaluated the correlation of ADAM8 expression with the clinicopathological features and prognosis in the patients with gliomas. Immunohistochemistry and western blot were used to investigate the expression of ADAM8 protein, respectively, in 128 patients with gliomas. The expression levels of ADAM8 in glioma tissues were significantly higher (P = 0.002) than those in non-neoplastic brain tissues according to the immunohistochemistry analysis. In addition, a high level of ADAM8 expression was significantly more common in glioma tissues with advanced grade than those with low grade (P = 0.01), which were in line with the results of western blot analysis (P = 0.01). Moreover, the increased expression of ADAM8 was significantly correlated with low Karnofsky performance score (KPS) (P = 0.008), frequent intra-tumor necrosis (P = 0.01), and poor overall survival (P = 0.008). Furthermore, multivariate analysis identified the expression levels of ADAM8 (P = 0.01) and intra-tumor necrosis (P = 0.03) to be independent prognostic factors. These findings suggest for the first time that ADAM8 is frequently overexpressed in human gliomas and is closely associated with poor clinical outcome. PMID- 21983885 TI - Role and interaction of p53, BAX and the stress-activated protein kinases p38 and JNK in benzo(a)pyrene-diolepoxide induced apoptosis in human colon carcinoma cells. AB - Polycyclic aromatic hydrocarbons are ubiquitous environmental pollutants formed during incomplete combustion of organic material. For example benzo[a]pyrene (B[a]P) is a constituent and contaminant of cigarette smoke, automobile exhaust, industrial waste and even food products. B[a]P is carcinogenic to rodents and humans. B[a]P induces its own metabolism, which generates different metabolites such as the highly reactive electrophilic genotoxin and ultimal carcinogen B[a]P 7,8-dihydrodiol-9,10-epoxide (BPDE). BPDE can bind to nucleophilic macromolecules such as proteins and DNA and causes mutations. Multiple defence mechanisms have evolved to protect the cell from DNA damage. Specific signalling pathways operate to detect and repair different kinds of lesions. In case, the damage is poorly removed expansion of damaged cells can be counteracted, e.g., by the inhibition of proliferation or triggering apoptosis. Examples of damage sensors and transducers are stress-activated protein kinases (SAPKs) and the tumour suppressor protein p53. Here, we studied the role of p53 and the pro-apoptotic protein BAX in BPDE-induced cell death by using wild-type- or knock-out-human colon carcinoma cells. As reported previously, we could reconfirm a critical role of p53 in BPDE-induced apoptosis. Furthermore, induced levels of total p53 and its transcriptional target p21 declined at higher BPDE concentrations correlating with reduced rates of apoptosis. Interestingly, increased phosphorylation of p53 at serine 15 remained elevated at higher BPDE concentrations thus disconnecting p53 phosphorylation from downstream apoptosis. Hence, phosphorylation of p53 seems not only to be a more sensitive biomarker of BPDE exposure but might serve other functions unrelated to apoptosis. In addition, we identify BAX as a novel and essential factor to trigger the intrinsic pathway of apoptosis in response to BPDE. Furthermore, BPDE in parallel activates the SAPKs p38 and JNK, which are as well involved in apoptosis. Although several routes of mutual regulation of p53 and SAPK have been described, we present evidence that the SAPK pathway in response to genotoxic stress can unexpectedly operate independently of p53 and controls apoptosis by a novel mechanism possibly downstream of caspases. PMID- 21983886 TI - Association between polymorphisms of EPHX1 and XRCC1 genes and the risk of childhood acute lymphoblastic leukemia. AB - Microsomal epoxide hydrolase, EPHX1, plays a central role in the detoxification of potentially genotoxic epoxide intermediates. In this study, we firstly aimed to investigate the relationship between EPHX1 Tyr113His and His139Arg variants, and the risk of incidence of childhood acute lymphoblastic leukemia (ALL) in Turkish population, comprised of 190 healthy controls and 167 ALL patients. In exon 3 Tyr113His polymorphism, 113His/His homozygous mutant genotype with slow activity was 18.6% in ALL patients and 9% in controls, indicating 113His/His slow activity genotype was significantly associated with an increased risk of childhood ALL (OR: 2.3, 95% CI, 1.2-4.4, P = 0.01). No significant association was found between exon 4 His139Arg variant and the risk of ALL. When both exon 3 Tyr113His and exon 4 His139Arg polymorphisms were considered together, only the exon 3 113His/His, homozygous mutant, slow activity genotype with exon 4 wild type genotype 139His/His was significantly increased the risk of ALL 2.4-fold (OR: 2.4, P = 0.02). We also evaluated whether haplotype analysis for EPHX1 Tyr113His polymorphism together with DNA protein XRCC1 Arg399Gln variant known for its deficient DNA repair capacity would represent more prominent risk factors for the development of childhood ALL. Accordingly, the co-presence of Tyr113His variant of EPHX1 and Arg399Gln variant of XRCC1 in the same individuals significantly increased the risk of childhood ALL up to 2.1-fold (OR = 2.1, P = 0.03). Moreover, homozygous mutant genotype for both genes significantly and considerably increased the risk of childhood ALL 8.5-fold (OR: 8.5, P = 0.03). In conclusion, individuals with EPHX1 113His/His slow activity genotype may not detoxify reactive carcinogenic epoxides efficiently, binding of reactive epoxides to DNA cause DNA damage. With the inadequate polymorphic DNA repair protein, XRCC1, this situation ultimately leads to significantly increased susceptibility for childhood ALL. PMID- 21983887 TI - The field of tension between toxicology and basic and clinical sciences. PMID- 21983888 TI - Physiological effects of arsenate on transplant thalli of the lichen Pyxine cocoes (Sw.) Nyl. AB - INTRODUCTION: The changes in photosynthetic pigments, chlorophyll fluorescence, protein content, and antioxidant enzymes were investigated in a foliose lichen Pyxine cocoes, which was subjected to increasing concentrations of arsenate. METHODS: The arsenate concentrations of 10, 25, 50, 75, 100, and 200 MUM were sprayed every alternate day on the lichen thallus. The thalli were then harvested on 10, 20, 30, and 45 days. RESULTS: The quantity of photosynthetic pigments exhibited a decreasing trend till 20 days but increased from 30 days onwards. Concomitantly, chlorophyll fluorescence also showed a decreasing trend with increasing arsenic treatment duration as well as concentration. The higher concentration of arsenate was found to be deleterious to the photosynthesis of lichen as the chlorophyll fluorescence and the amount of pigments decreased significantly. The protein content of lichen increased uninterruptedly as the concentration of arsenate as well as duration of treatment increased. The activities of superoxide dismutase and ascorbate peroxide increased initially at lower concentration of arsenate but declined at higher concentrations and longer duration of treatment. CONCLUSIONS: The catalase activity was found to be most susceptible to arsenate stress as its activity started declining from very beginning of the experiment. P. cocoes also proved to be an excellent accumulator of arsenate whose concentration increased in the thallus corresponding to its increase in the treatment and duration. Thus, it can be utilized for active biomonitoring of arsenic pollution. PMID- 21983889 TI - Molecular control of quantum-dot internal electric field and its application to CdSe-based solar cells. AB - Inorganic nanocrystals are attractive materials for solar-cell applications. However, the performance of such devices is often limited by an insufficient alignment of energy levels in the nanocrystals. Here, we report that by attaching two different molecules to a single quantum dot or nanocrystal one can induce electric fields large enough to significantly alter the electronic and optoelectronic properties of the quantum dot. This electric field is created within the nanocrystals owing to a mixture of amine- and thiol-anchor-group ligands. Examining the steady state as well as temporal evolution of the optical properties and the nuclear magnetic resonances of the nanocrystals we found that the first excitonic peak shifts as a function of the capping-layer composition. We also demonstrate that the use of a mixed-ligand-induced electric field markedly enhances the charge generation efficiency in layer-by-layer CdSe nanocrystal-based solar cells, thus improving the overall cell efficiency. PMID- 21983890 TI - Self-assembly of highly ordered conjugated polymer aggregates with long-range energy transfer. AB - Applications of conjugated polymers (CP) in organic electronic devices such as light-emitting diodes and solar cells depend critically on the nature of electronic energy transport in these materials. Single-molecule spectroscopy has revealed their fundamental properties with molecular detail, and recent reports suggest that energy transport in single CP chains can extend over extraordinarily long distances of up to 75 nm. An important question arises as to whether these characteristics are sustained when CP chains agglomerate into a neat solid. Here, we demonstrate that the electronic energy transport in aggregates composed of tens of polymer chains takes place on a similar distance scale as that in single chains. A recently developed molecular-level understanding of solvent vapour annealing has allowed us to develop a technique to control the CP agglomeration process. Aggregates with volumes of at least 45,000 nm(3) (molecular weight ~ 21 MDa) maintain a highly ordered morphology and show pronounced fluorescence blinking behaviour, indicative of substantially long-range energy transport. Our findings provide a new lens through which the ordering of single CP chains and the evolution of their morphological and optoelectronic properties can be observed, which will ultimately enable the rational design of improved CP-based devices. PMID- 21983891 TI - Dynamic contour tonometry and goldman applanation tonometry: correlation with intracameral assessment of intraocular pressure. PMID- 21983893 TI - Phase I trial of preoperative intratumoral injection of immature dendritic cells and OK-432 for resectable pancreatic cancer patients. AB - PURPOSE: To determine the feasibility, safety and histological change of preoperative endoscopic ultrasound-guided fine-needle injection (PEU-FNI) of immature DCs (iDCs) with OK-432 in pancreatic cancer patients. METHODS: Nine patients enrolled in the trial (DC group) and were compared with 15 patients operated on without iDC injection (non-DC group). Adverse events of PEU-FNI and postoperative complications were evaluated according to CTC-AE ver.3.0 and the Clavien-Dindo classification/ISGPF definition, respectively. Histological changes within the tumor and lymph nodes were evaluated by immunohistochemical examination of infiltrating inflammatory cells (CD4+, CD8+, Foxp3+ and CD83+). RESULTS: There were no severe toxicities following PEU-FNI, except for one transient grade 3 fever, and there were no significant differences in the incidence of postoperative complications between the two groups. Colliquative necrosis and diffusely scattered TUNEL-positive cells were observed at the injection sites. CD83+ cells significantly accumulated in the regional lymph nodes of the DC group as well as Foxp3+ cells in the regional and distant lymph nodes. The two DC group patients, one of which was stage IV with distant lymph node metastasis, survived more than 5 years without requiring adjuvant theraphy. CONCLUSION: PEU-FNI was feasible and safe, and further study needs to confirm and enhance antitumor responses. PMID- 21983892 TI - Preoperative MRCP to detect choledocholithiasis in acute calculous cholecystitis. AB - PURPOSE: There are risks of common bile duct (CBD) stones in acute cholecystitis, and there is a move among surgeons to identify choledocholithiasis before surgery. Magnetic resonance cholangiopancreaticography (MRCP) has the potential to accurately detect choledocholithiasis in patients with acute cholecystitis. The aim of this study was to evaluate the predictive values of MRCP and elevated biochemical predictors for choledocholithiasis in patients with acute cholecystitis. METHODS: Between September 2006 and August 2008, of 84 patients with acute cholecystitis based on the diagnosis criteria of the Tokyo guidelines, 57 had MRCP preoperatively. The predictive values of six biochemical predictors for choledocholithiasis were also evaluated. RESULTS: Of the 57 patients, seven (12.28%) had choledocholithiasis, of whom three had CBD stones in nondilated ducts. The smallest stone detected in a dilated CBD and nondilated duct was 3.19 and 4.55 mm in diameter, respectively. None of our patients whose MRCP showed a clear CBD returned with symptomatic choledocholithiasis during the follow-up period. All biochemical predictors and CBD diameter had limited positive predictive values. CONCLUSIONS: Magnetic resonance cholangiopancreaticography is a reliable evaluation technique for the detection of choledocholithiasis. It reduces the misdiagnosis of retained choledocholithiasis with normal biochemical predictors and prevents the risk of overlooking choledocholithiasis. No single predictor or combined markers have been found to be reliable for including/excluding the presence of choledocholithiasis. PMID- 21983894 TI - Negative impact of low body mass index on surgical outcomes after hepatectomy for hepatocellular carcinoma. AB - BACKGROUND: Studies have previously indicated that surgical outcomes are poorer for obese patients. To date, few reports concerning the effect of obesity on patient outcomes following a hepatectomy for hepatocellular carcinoma (HCC) have been published. The present study, therefore, sought to determine the impact of patients' body mass index (BMI, kg/m(2)) on short- and long-term surgical outcomes and to identify potential prognostic factors for HCC following a hepatectomy. METHODS: Patient data was retrospectively collected from 181 consecutive patients between September 2002 and August 2007 who had undergone hepatectomy for HCC with curative intent. Patients were assigned to three groups according to their BMI (low <18.5, standard 18.5-25, and high >25), and the clinical and pathological data, surgical outcome, and long-term survival were analyzed and compared between the three groups. RESULTS: The overall survival rate of the low BMI group was notably below that of the standard group. Surgical outcomes were not significantly different between the three groups. Multivariate analysis revealed that a low BMI (<18.5) is a predictor of unfavorable prognosis. CONCLUSIONS: The present study suggests that a low BMI is a significant prognostic factor for low overall survival when performing a hepatectomy for HCC. PMID- 21983895 TI - Impact of healthcare-associated acquisition on community-onset Gram-negative bloodstream infection: a population-based study: healthcare-associated Gram negative BSI. AB - We performed a population-based study to examine the influence of healthcare associated acquisition on pathogen distribution, antimicrobial resistance, short- and long-term mortality of community-onset Gram-negative bloodstream infections (BSI). We identified 733 unique patients with community-onset Gram-negative BSI (306 healthcare-associated and 427 community-acquired) among Olmsted County, Minnesota, residents from 1 January 1998 to 31 December 2007. Multivariate logistic regression was used to examine the association between healthcare associated acquisition and microbiological etiology and antimicrobial resistance. Multivariate Cox proportional hazards regression was used to evaluate the influence of the site of acquisition on mortality. Healthcare-associated acquisition was predictive of Pseudomonas aeruginosa (odds ratio [OR] 3.14, 95% confidence intervals [CI]: 1.59-6.57) and the group of Enterobacter, Citrobacter, and Serratia species (OR 2.23, 95% CI: 1.21-4.21) as causative pathogens of community-onset Gram-negative BSI. Healthcare-associated acquisition was also predictive of fluoroquinolone resistance among community-onset Gram-negative bloodstream isolates (OR 2.27, 95% CI: 1.18-4.53). Healthcare-associated acquisition of BSI was independently associated with higher 28-day (hazard ratio [HR] 3.73, 95% CI: 2.13-6.93) and 1-year mortality (HR 3.60, 95% CI: 2.57-5.15). Because of differences in pathogen distribution, antimicrobial resistance, and outcomes between healthcare-associated and community-acquired Gram-negative BSI, identification of patients with healthcare-associated acquisition of BSI is essential to optimize empiric antimicrobial therapy. PMID- 21983896 TI - Dynamics of interferon-gamma release assay and cytokine profiles in blood and respiratory tract specimens from mice with tuberculosis and the effect of therapy. AB - There are limitations on diagnostic methods to differentiate between active and latent tuberculosis (TB), and the prediction of latent progression to TB disease is yet complex. Traditionally, tuberculosis-specific host immune response was visualized using the tuberculin skin test. Nowadays, IFN-gamma release assays (IGRA) provide a more specific and sensitive tool, by which exposure to Mtb could be determined. However, the merit of IGRA aids in diagnosing active TB is yet unclear. We adapted IGRA for use in mice, and quantifying bead-based flow cytometry techniques were used to assess cytokine profiles during the course of untreated infection and to investigate the value of IGRA and cytokines as biomarkers for therapy response. High variability of IGRA results during progression of active TB infection related to various phases of infection was obtained. However, a significant decrease in IGRA results and in levels of IFN gamma, IL-17, IP-10 or MIG was observed and appeared to be associated with successful therapy. This outcome does not support the value of IGRA to accurately diagnose active TB or to monitor infection progression. However, IGRA proved to be a useful biomarker to monitor therapy success. In addition, different cytokines might serve as biomarkers. PMID- 21983898 TI - p66Shc-dependent apoptosis requires Lck and CamKII activity. AB - p66Shc, an adaptor molecule which enhances reactive oxygen species (ROS) production by mitochondria, promotes T-cell apoptosis by inducing mitochondrial dysfunction and impairing Ca(2+) homeostasis. We have addressed the potential role of Lck, a kinase which has been implicated in T-cell apoptosis induced by a number of stimuli, in the proapoptotic activity of p66Shc. Lck deficiency in Jurkat T cells overexpressing p66Shc leads to impaired apoptotic responses to supraphysiological increases in [Ca(2+)](c). This defect could be rescued by reconstitution of Lck expression, indicating that Lck is required for p66Shc dependent apoptosis. Furthermore, p66Shc phosphorylation on serine 36 (S36), an event on which the proapoptotic function of p66Shc depends, requires Lck. p66Shc dependent mitochondrial dysfunction, altered Ca(2+) homeostasis and S36 phosphorylation require moreover the activity of CaMKII, a Ca(2+)/calmodulin dependent kinase known to be implicated in the proapoptotic activity of Lck in T cells. The results suggest that increases in [Ca(2+)](c) lead to CaMKII activation and subsequent Lck-dependent p66Shc phosphorylation on S36. This event causes both mitochondrial dysfunction and impaired Ca(2+) homeostasis, which synergize in promoting Jurkat T-cell apoptosis. PMID- 21983899 TI - Incorporation of active metal sites in MOFs via in situ generated ligand deficient metal-linker complexes. AB - Two novel 3D MOFs, namely MOF-647A and MOF-648 (previously unknown trinodal 4 connected net), comprised of Cu ions and pyrazole-3,5-dicarboxylate were synthesized and characterized. A strategy for incorporating open metal sites in MOFs was investigated by utilizing an in situ generated metal-linker complex as a precursor to construct MOF-648. PMID- 21983901 TI - Optic atrophy 1 is an A-kinase anchoring protein on lipid droplets that mediates adrenergic control of lipolysis. AB - Adrenergic stimulation of adipocytes yields a cAMP signal that activates protein kinase A (PKA). PKA phosphorylates perilipin, a protein localized on the surface of lipid droplets that serves as a gatekeeper to regulate access of lipases converting stored triglycerides to free fatty acids and glycerol in a phosphorylation-dependent manner. Here, we report a new function for optic atrophy 1 (OPA1), a protein known to regulate mitochondrial dynamics, as a dual specificity A-kinase anchoring protein associated with lipid droplets. By a variety of protein interaction assays, immunoprecipitation and immunolocalization experiments, we show that OPA1 organizes a supramolecular complex containing both PKA and perilipin. Furthermore, by a combination of siRNA-mediated knockdown, reconstitution experiments using full-length OPA1 with or without the ability to bind PKA or truncated OPA1 fused to a lipid droplet targeting domain and cellular delivery of PKA anchoring disruptor peptides, we demonstrate that OPA1 targeting of PKA to lipid droplets is necessary for hormonal control of perilipin phosphorylation and lipolysis. PMID- 21983900 TI - SET8 promotes epithelial-mesenchymal transition and confers TWIST dual transcriptional activities. AB - SET8 is implicated in transcriptional regulation, heterochromatin formation, genomic stability, cell-cycle progression, and development. As such, it is predicted that SET8 might be involved in the development and progression of tumour. However, whether and how SET8 might be implicated in tumourigenesis is currently unknown. Here, we report that SET8 is physically associated with TWIST, a master regulator of epithelial-mesenchymal transition (EMT). We demonstrated that SET8 and TWIST are functionally interdependent in promoting EMT and enhancing the invasive potential of breast cancer cells in vitro and in vivo. We showed that SET8 acts as a dual epigenetic modifier on the promoters of the TWIST target genes E-cadherin and N-cadherin via its H4K20 monomethylation activity. Significantly, in breast carcinoma samples, SET8 expression is positively correlated with metastasis and the expression of TWIST and N-cadherin and negatively correlated with E-cadherin. Together, our experiments revealed a novel role for SET8 in tumour invasion and metastasis and provide a molecular mechanism underlying TWIST-promoted EMT, suggesting SET8 as a potential target for intervention of the metastasis of breast cancer. PMID- 21983902 TI - Confirmation of R132H mutation of isocitrate dehydrogenase 1 as an independent prognostic factor in anaplastic astrocytoma. PMID- 21983904 TI - [Case management for moderate-need patients and recovery: what can we learn from experimental and quasi-experimental studies?]. AB - How should case management be organized for people who have severe mental illness, but do not need Assertive Community Treatment or similar high-intensity programs? To address this question, the authors conducted a systematic review of studies published in English between 1980 and 2010. Five main case management models were identified: broker, clinical case management, rehabilitation, strengths and intensive case management. In all, 11 experimental and 13 quasi experimental studies evaluating case management programs not targeted at a typical ACT clientele were identified. These studies suggest that the strengths model, which can be viewed as a way of structuring intensive case management for a moderate-need population, is the best supported by evidence if one desires to see effects not only on hospital days, but also on other domains such as symptoms, quality of life and social functioning. It is also compatible with a recovery orientation. The evidence in its favor, however, remains modest. PMID- 21983905 TI - [New parameters in community treatment practices: the contribution of community and alternative mental health groups in Quebec]. AB - This article examines the origin and the context of the implementation project of community treatment according to the perspective of community and alternative mental health groups in Quebec. The author presents results of a research on practices of these groups through a specific array that integrates the essential components of the community treatment model. The author examines six parameters characterizing devices, approaches and practices: 1) approach in supportive care and attention; 2) voluntary relation with the organization 3) the place of biomedical treatment; 4) flexibility in length and intensity of treatment; 5) the individual and collective dimension of supportive care; 6) and, participation as an active citizen. PMID- 21983903 TI - Remission after treatment of osteoarticular infections due to Pseudomonas aeruginosa versus Staphylococcus aureus: a case-controlled study. AB - PURPOSE: Osteoarticular infections due to methicillin-susceptible Staphylococcus aureus (MSSA) or its methicillin-resistant variant (MRSA) are feared due to treatment failures. According to clinical experience, Pseudomonas aeruginosa may reveal less long-term remission than S. aureus. METHODS: A case-controlled study comparing outcomes of osteoarticular infections due to P. aeruginosa vs S. aureus was performed at Geneva University Hospitals. RESULTS: A total of 111 S. aureus (including 37 MRSA) and 20 P. aeruginosa osteoarticular infections were analysed in 131 patients: arthroplasties (n = 38), fracture fixation devices (n = 56), native joint arthritis (n = 7) and osteomyelitis without implant (n = 30). The median active follow-up time was 4 years. The patients underwent a median number of two surgical interventions for P. aeruginosa infections compared to two for S. aureus (two for MRSA), while the median duration of antibiotic treatment was 87 days for P. aeruginosa and 46 days for S. aureus infections (58 days for MRSA) (all p > 0.05). Overall, Pseudomonas-infected patients tended towards a lower remission rate than those infected with S. aureus (12/20 vs 88/111; p = 0.06). This was similar when P. aeruginosa was compared with MRSA alone (12/20 vs 30/37; p = 0.08). In multivariate logistic regression analyses adjusting for case mix, odds ratios (OR) for remission were as follows: P. aeruginosa vs S. aureus [OR 0.4, 95% confidence interval (CI) 0.1-1.2], number of surgical interventions (OR 0.6, 95% CI 0.5-1.0) and duration of antibiotic treatment (OR 1.0, 95% CI 1.0 1.0). CONCLUSIONS: Despite a similar number of surgical interventions and longer antibiotic treatment, osteoarticular infections due to P. aeruginosa tended towards a lower remission rate than infections due to S. aureus in general or MRSA in particular. PMID- 21983906 TI - [Revisiting the therapeutic experience in a psychiatric day hospital six months after discharge: path and perceptions of people with mental disorders]. AB - This article presents a qualitative study on the therapeutic experience in a psychiatric day hospital six months after discharge. The study explores the impact of this experience on the lives of people with mental disorders. A qualitative design using semi-structured individual interviews was completed with 18 participants six months after their discharge of a day hospital. Results showed that the day hospital experience was particularly helpful to improve symptoms and relationship with self. It activated a self-transformational process that continued afterwards. Termination created for many, an abrupt void. Issues at stake during the first six months were continuity of care, social support and maintaining skills and knowledge acquired. PMID- 21983907 TI - [Revisiting the notion of treatment in mental health from the perspective of consumers and stakeholders of alternative community treatment resources: the issue of subjectivity]. AB - This article examines the importance of subjectivity and its complexity in psychiatric and mental health care. The question of subjectivity appears quite marginalized in current debates, especially in North America. The authors question the tendency to disregard subjectivity in mental health care and treatment. Results of a qualitative study with consumers and stakeholders of non institutional organizations identified as alternative community treatment resources, show that point of views meet regarding comprehension of treatment, thus increasing the interest and the scope of this study's findings. PMID- 21983908 TI - [Puberty, body image and dysfunctional attitudes: differences between boys and girls in depressive symptoms during the transition from elementary to secondary education]. AB - The objective of this longitudinal study was to examine the emergence of differences in girls and boys in depressive symptoms during the transition from elementary to secondary school. Four hundred and ninety nine adolescents followed through the last grade of primary school and the first year of secondary school completed measures of pubertal status, body image, dysfunctional attitudes and depressive symptoms. Results show that puberty and body image slightly mediated the relationship between sex and depressive symptoms and that dysfunctional attitudes did not mediate the relationship between puberty lived during transition to secondary school and depression. Results also demonstrate the importance of better understanding the impact of transition to secondary school on adolescents' depressive symptoms. PMID- 21983909 TI - [Eating disorders (ED) and obsessive-compulsive disorders (OCD): common factors]. AB - Several similarities exist in the phenomenology of obsessive-compulsive disorder (OCD) and eating disorders (ED : anorexia nervosa and bulimia). Both disorders include obsessive thoughts and compulsive or ritualized behaviours. Furthermore, these two disorders frequently present with similar comorbid disorders. In this article, the authors examine similarities between ED and OCD, and whether eating disorders can be conceptualized as a variant of obsessive-compulsive disorders. This raises the possibility that treatments proven effective for OCD could be successfully adapted for ED. The authors consequently further examine both treatments utilized for both disorders. PMID- 21983910 TI - [Integration in the workforce of Quebec of adults living with Autism Spectrum Disorder or Asperger Syndrome]. AB - This article presents an exploratory study evaluating the impact of the program Employment Pact: Quebec in full force (2008) aimed at the integration in the workforce of adults living with Autism Spectrum Disorder (ASD) or Asperger Syndrome (AS). This program is implemented in different regions in Quebec. The evaluation takes into consideration working conditions, integration procedures, as well as receptivity of eventual employers. Results demonstrate that the working conditions for these individuals are relatively similar, however, the type and number of services offered, as well as the training of service agents vary from one centre to another. PMID- 21983911 TI - [Methods of psychotherapy case studies: current perspectives]. AB - There is a renewal of interest among psychotherapy researchers and psychotherapists towards psychotherapy case studies. This article presents two paradigms that have greatly influenced this increasing interest in psychotherapy case studies : the pragmatic case study and the theory-building case study paradigm. The origins, developments and key-concepts of both paradigms are presented, as well as their methodological and ethical specificities. Examples of case studies, along with models developed, are cited. The differential influence of the post-modern schools on both paradigms are presented, as well as their contribution to the field of methods of psychotherapy case studies discussed and assessed in terms of relevance for the researcher and the psychotherapist. PMID- 21983912 TI - [Understanding dissociation in patients with borderline personality disorder]. AB - Dissociation is a disturbing psychiatric concept fraught with controversy. It is however encountered in clinical contexts and has to be understood by clinicians. This article based on a Pubmed/Ovid on line research with key words dissociation and borderline personality disorder and other references, describes the clinical aspects of the dissociative phenomena in patients with borderline personality disorder. Psychodynamic hypotheses and neurophysiological data are examined to explain dissociation. Neurophysiological and neuroanatomical variables provided by cerebral imagery controlled studies support hypotheses brought forward. The article concludes with a defence mechanism developed within a context of biological predisposition, deprived psychological development and in reaction to trauma. In conclusion, emerging psychotherapeutic solutions are summarized. PMID- 21983913 TI - Genetic diversity of Fusarium oxysporum f.sp. cubense isolates (Foc) of India by inter simple sequence repeats (ISSR) analysis. AB - To find out the genetic diversity of Indian Foc isolates of banana, a total of 107 isolates of Fusarium which includes 98 Foc isolates obtained from different banana growing regions of India and seven Foc isolates belong to all known VCGs obtained from Australia and two non-pathogenic Fusarium oxysporum (npFo) isolates were subjected to ISSR analysis. In the initial screening of ISSR primers, out of 34, 10 primers which generated more polymorphic bands were selected for further analysis. The Phylogenetic analysis carried out based on the fingerprints obtained through ISSR analysis indicated the presence of wide genetic diversity among the Foc isolates of India and also its polyphyletic nature. Totally, seven different clusters were obtained and these clusters differentiated the Foc isolates of India based on the races/VCGs. Besides, the cluster analysis clearly distinguished the freshly emerged Foc strain obtained from cv. Grand Naine (Cavendish-AAA) and Poovan (Mysore-AAB) from the other Foc isolates. The non pathogenic F. oxysporum isolates which have been included for comparison purpose also clustered separately. All these above said findings indicates for the first time the discriminatory power of ISSR to clearly distinguish and separate the Foc isolates according to its race/VCGs and also its virulence. This study would be useful not only to design and develop effective management strategies but also useful for quarantine purposes. PMID- 21983914 TI - A two-stage estimation in the Clayton-Oakes model with marginal linear transformation models for multivariate failure time data. AB - This paper considers the analysis of multivariate survival data where the marginal distributions are specified by semiparametric transformation models, a general class including the Cox model and the proportional odds model as special cases. First, consideration is given to the situation where the joint distribution of all failure times within the same cluster is specified by the Clayton-Oakes model (Clayton, Biometrika 65:141-151, l978; Oakes, J R Stat Soc B 44:412-422, 1982). A two-stage estimation procedure is adopted by first estimating the marginal parameters under the independence working assumption, and then the association parameter is estimated from the maximization of the full likelihood function with the estimators of the marginal parameters plugged in. The asymptotic properties of all estimators in the semiparametric model are derived. For the second situation, the third and higher order dependency structures are left unspecified, and interest focuses on the pairwise correlation between any two failure times. Thus, the pairwise association estimate can be obtained in the second stage by maximizing the pairwise likelihood function. Large sample properties for the pairwise association are also derived. Simulation studies show that the proposed approach is appropriate for practical use. To illustrate, a subset of the data from the Diabetic Retinopathy Study is used. PMID- 21983915 TI - Entadosides A-D, triterpene saponins and a glucoside of the sulphur-containing amide from the kernel nuts of Entada phaseoloides (L.) Merrill. AB - From a MeOH extract of kernel nuts of Entada phaseoloides (L.) Merrill, one new and one known sulphur-containing glucoside were isolated. From the 1-BuOH-soluble fraction of a H(2)O extract, four new triterpene saponins containing N acetylglucosamine in their sugar chains were isolated. The antiproliferative activities of the triterpene saponins were assayed. PMID- 21983916 TI - Mindfulness-based cognitive therapy for people with chronic fatigue syndrome still experiencing excessive fatigue after cognitive behaviour therapy: a pilot randomized study. AB - Cognitive behaviour therapy (CBT) is an effective treatment for chronic fatigue syndrome (CFS; sometimes known as myalgic encephalomyelitis). However, only a minority of patients fully recover after CBT; thus, methods for improving treatment outcomes are required. This pilot study concerned a mindfulness-based cognitive therapy (MBCT) intervention adapted for people with CFS who were still experiencing excessive fatigue after CBT. The study aimed to investigate the acceptability of this new intervention and the feasibility of conducting a larger scale randomized trial in the future. Preliminary efficacy analyses were also undertaken. Participants were randomly allocated to MBCT or waiting list. Sixteen MBCT participants and 19 waiting-list participants completed the study, with the intervention being delivered in two separate groups. Acceptability, engagement and participant-rated helpfulness of the intervention were high. Analysis of covariance controlling for pre-treatment scores indicated that, at post treatment, MBCT participants reported lower levels of fatigue (the primary clinical outcome) than the waiting-list group. Similarly, there were significant group differences in fatigue at 2-month follow-up, and when the MBCT group was followed up to 6 months post-treatment, these improvements were maintained. The MBCT group also had superior outcomes on measures of impairment, depressed mood, catastrophic thinking about fatigue, all-or-nothing behavioural responses, unhelpful beliefs about emotions, mindfulness and self-compassion. In conclusion, MBCT is a promising and acceptable additional intervention for people still experiencing excessive fatigue after CBT for CFS, which should be investigated in a larger randomized controlled trial. KEY PRACTITIONER MESSAGE: Only about 30% of people with chronic fatigue syndrome (CFS) recover after cognitive behaviour therapy (CBT); thus, methods for improving treatment outcomes are needed. This is the first pilot randomized study to demonstrate that a mindfulness-based intervention was associated with reduced fatigue and other benefits for people with CFS who were still experiencing excessive fatigue after a course of CBT. Levels of acceptability, engagement in the intervention and rated helpfulness were high. A larger-scale randomized controlled trial is required. PMID- 21983917 TI - Differences in delay discounting between smokers and nonsmokers remain when both rewards are delayed. AB - RATIONALE: When offered a choice between a small monetary reward available immediately (SmallNow) versus a larger reward available after a delay (LargeLater), smokers select the SmallNow alternative more than nonsmokers. That is, smokers discount the value of the LargeLater reward more than nonsmokers. OBJECTIVES: To investigate whether this group difference was due to smokers overweighting the value of rewards available immediately compared with nonsmokers, we examined whether the group difference was also seen when both alternatives were delayed, i.e., when choosing between a SmallSoon reward and a LargeLater reward. METHODS: In Experiment 1, smokers and nonsmokers completed a task including SmallNow versus LargeLater choices and SmallSoon versus LargeLater choices. In Experiment 2, smokers and nonsmokers completed the same task but with hypothetical choices. RESULTS: Analyses using hyperbolic and double exponential (beta-delta) models replicate prior findings that smokers discount the LargeLater reward more than nonsmokers when the smaller reward is available immediately. The smoker-nonsmoker difference was also seen when the smaller reward was slightly delayed, though this effect was primarily driven by heightened discounting in male smokers. However, for potentially real rewards only, this smoker-nonsmoker difference was significantly reduced when the smaller reward was delayed. CONCLUSIONS: The smoker-nonsmoker difference in discounting is not confined to situations involving immediate rewards. Differences associated with potentially real versus hypothetical rewards and gender underscore the complexity of the smoking-delay discounting relationship. PMID- 21983919 TI - Incidence and seroprevalence of dengue virus infections in Australian travellers to Asia. AB - The purpose of this study was to estimate the incidence density and prevalence of dengue virus infection in Australian travellers to Asia. We conducted a multi centre prospective cohort study of Australian travellers over a 32-month period. We recruited 467 travellers (>= 16 years of age) from three travel clinics who intended to travel Asia, and 387 (82.9%) of those travellers completed questionnaires and provide samples pre- and post-travel for serological testing for dengue virus infection. Demographic data, destination countries and history of vaccinations and flavivirus infections were obtained. Serological testing for dengue IgG and IgM by enzyme-linked immunosorbent assay (ELISA) (PanBio assay) was performed. Acute seroconversion for dengue infection was demonstrated in 1.0% of travellers, representing an incidence of 3.4 infections per 10,000 days of travel (95% confidence interval [CI]: 0.9-8.7). The seroprevalence of dengue infection was 4.4% and a greater number of prior trips to Asia was a predictor for dengue seroprevalence (p = 0.019). All travellers experienced subclinical dengue infections and had travelled to India (n = 3) and China (n = 1). This significant attack rate of dengue infection can be used to advise prospective travellers to dengue-endemic countries. PMID- 21983918 TI - Intracranial self-stimulation in FAST and SLOW mice: effects of alcohol and cocaine. AB - RATIONALE: Sensitivity to the stimulant and rewarding effects of alcohol may be genetically correlated traits that predispose individuals to develop an alcohol use disorder. OBJECTIVE: This study aimed to examine the effects of alcohol and cocaine on intracranial self-stimulation (ICSS) in FAST and SLOW mice, which were selectively bred for extremes in alcohol stimulation. METHODS: Male FAST and SLOW mice were conditioned to respond for reinforcement by direct electrical stimulation of the medial forebrain bundle (i.e., brain stimulation reward). ICSS responses were determined immediately before and after oral gavage with water or alcohol (0.3-2.4 g/kg) or intraperitoneal injection with saline or cocaine (1.0 30.0 mg/kg). In separate FAST and SLOW mice, the locomotor effects of these treatments were measured in activity chambers. RESULTS: Alcohol dose-dependently lowered the threshold for self-stimulation (theta (0)) and the frequency that maintained 50% of maximal responding (EF50) in FAST mice but did not significantly affect these parameters in SLOW mice. The largest effects of alcohol were after the 1.7- and 2.4-g/kg doses and were about 40% compared to water injection. Alcohol did not affect MAX response rates, but dose-dependently stimulated locomotor activity in FAST mice. Cocaine lowered thresholds equally in FAST and SLOW mice, although cocaine-stimulated locomotor activity was higher in the FAST than in the SLOW mice. CONCLUSIONS: Selective breeding for alcohol locomotor stimulation also renders the mice more sensitive to the effects of alcohol, but not cocaine, on ICSS. PMID- 21983920 TI - Reemerging of enterovirus 71 in Taiwan: the age impact on disease severity. AB - Enterovirus 71 (EV71) infection commonly strike children under the age of 3 years, with an occasionally unfavorable outcome in children. This study was designed to explore the relationship between age and the severity of complications, which may associate with antibody-dependent enhancement (ADE) in EV71. All EV71-infected patients during the outbreak of 2008 were recruited. In total, 134 patients were enrolled and categorized into two age groups, 0-12 months (n = 18) and >12 months (n = 116). Pulmonary edema/hemorrhage more commonly occur in patients younger than 12 months. No difference in the occurrence of herpangina/hand-foot-and-mouth disease (HFMD), uncomplicated brainstem encephalitis (BE), or autonomic nervous system (ANS) dysregulation was noted between the two age groups. Patients with pulmonary edema/hemorrhage (11.9 +/- 14.7 months) were younger than patients with herpangina/HFMD (35.8 +/- 26.4 months) or ANS dysregulation (33.9 +/- 20.9 months). Our findings are in agreement with the data regarding the outbreak in Taiwan, in which a decrease in age corresponded to an increase in disease severity with regard to central nervous system complications. A reduction of maternal antibodies to the subneutralizing level within 1 year of age may be associated with the ADE of the infection. This study could provide possible clinical significance with regard to ADE phenomena in young infants infected by EV71. PMID- 21983921 TI - Population-specific expression analysis (PSEA) reveals molecular changes in diseased brain. AB - Human diseases are often accompanied by histological changes that confound interpretation of molecular analyses and identification of disease-related effects. We developed population-specific expression analysis (PSEA), a computational method of analyzing gene expression in samples of varying composition that can improve analyses of quantitative molecular data in many biological contexts. PSEA of brains from individuals with Huntington's disease revealed myelin-related abnormalities that were undetected using standard differential expression analysis. PMID- 21983922 TI - Surrogate reporters for enrichment of cells with nuclease-induced mutations. AB - Zinc-finger nucleases (ZFNs) and TAL-effector nucleases (TALENs) are powerful tools for creating genetic modifications in eukaryotic cells and organisms. But wild-type and mutant cells that contain genetic modifications induced by these programmable nucleases are often phenotypically indistinguishable, hampering isolation of mutant cells. Here we show that transiently transfected episomal reporters encoding fluorescent proteins can be used as surrogate genes for the efficient enrichment of endogenous gene-modified cells by flow cytometry. PMID- 21983923 TI - Artificial niche microarrays for probing single stem cell fate in high throughput. AB - To understand the regulatory role of niches in maintaining stem-cell fate, multifactorial in vitro models are required. These systems should enable analysis of biochemical and biophysical niche effectors in a combinatorial fashion and in the context of a physiologically relevant cell-culture substrate. We report a microengineered platform comprised of soft hydrogel microwell arrays with modular stiffness (shear moduli of 1-50 kPa) in which individual microwells can be functionalized with combinations of proteins spotted by robotic technology. To validate the platform, we tested the effect of cell-cell interactions on adipogenic differentiation of adherent human mesenchymal stem cells (MSCs) and the effect of substrate stiffness on osteogenic MSC differentiation. We also identified artificial niches supporting extensive self-renewal of nonadherent mouse neural stem cells (NSCs). Using this method, it is possible to probe the effect of key microenvironmental perturbations on the fate of any stem cell type in single cells and in high throughput. PMID- 21983924 TI - Mining the O-glycoproteome using zinc-finger nuclease-glycoengineered SimpleCell lines. AB - Zinc-finger nuclease (ZFN) gene targeting is emerging as a versatile tool for engineering of multiallelic gene deficiencies. A longstanding obstacle for detailed analysis of glycoproteomes has been the extensive heterogeneities in glycan structures and attachment sites. Here we applied ZFN targeting to truncate the O-glycan elongation pathway in human cells, generating stable 'SimpleCell' lines with homogenous O-glycosylation. Three SimpleCell lines expressing only truncated GalNAcalpha or NeuAcalpha2-6GalNAcalpha O-glycans were produced, allowing straightforward isolation and sequencing of GalNAc O-glycopeptides from total cell lysates using lectin chromatography and nanoflow liquid chromatography mass spectrometry (nLC-MS/MS) with electron transfer dissociation fragmentation. We identified >100 O-glycoproteins with >350 O-glycan sites (the great majority previously unidentified), including a GalNAc O-glycan linkage to a tyrosine residue. The SimpleCell method should facilitate analyses of important functions of protein glycosylation. The strategy is also applicable to other O glycoproteomes. PMID- 21983925 TI - Live-cell 3D super-resolution imaging in thick biological samples. AB - We demonstrate three-dimensional (3D) super-resolution live-cell imaging through thick specimens (50-150 MUm), by coupling far-field individual molecule localization with selective plane illumination microscopy (SPIM). The improved signal-to-noise ratio of selective plane illumination allows nanometric localization of single molecules in thick scattering specimens without activating or exciting molecules outside the focal plane. We report 3D super-resolution imaging of cellular spheroids. PMID- 21983927 TI - Treatment of nonalcoholic fatty liver disease in adults and children: a closer look at the arsenal. AB - Nonalcoholic fatty liver disease encompasses a spectrum of disease from asymptomatic steatosis, with or without elevated aminotransferases, to cirrhosis with relative complications and hepatocellular carcinoma. Owing to the increasing prevalence of nonalcoholic fatty liver disease and the potential for nonalcoholic steatohepatitis to progress to cirrhosis and liver-related mortality, more research has been focused on therapy of this important liver disease over the last two decades. To date, weight loss and physical activity represent the cornerstone of treatment, with interventions being limited to subjects at risk of disease progression, but the type of treatment remains a matter of debate. A few medications have shown promising results in preliminary pilot studies, but few agents have been tested rigorously. Today, multiple therapeutic approaches are considered the way to go in treating nonalcoholic steatohepatitis patients. In this paper we review the status of current and emerging therapeutic strategies for children and adult patients with nonalcoholic steatohepatitis. PMID- 21983928 TI - Detectability of colorectal neoplasia with fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography (FDG-PET/CT). AB - BACKGROUND: The purpose of this study was to analyze the detectability of colorectal neoplasia with fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT). METHODS: Data for a total of 492 patients who had undergone both PET/CT and colonoscopy were analyzed. After the findings of PET/CT and colonoscopy were determined independently, the results were compared in each of the six colonic sites examined in all patients. The efficacy of PET/CT was determined using colonoscopic examination as the gold standard. RESULTS: In all, 270 colorectal lesions 5 mm or more in size, including 70 pathologically confirmed malignant lesions, were found in 172 patients by colonoscopy. The sensitivity and specificity of PET/CT for detecting any of the colorectal lesions were 36 and 98%, respectively. For detecting lesions 11 mm or larger, the sensitivity was increased to 85%, with the specificity remaining consistent (97%). Moreover, the sensitivity for tumors 21 mm or larger was 96% (48/50). Tumors with malignant or high-grade pathology were likely to be positive with PET/CT. A size of 10 mm or smaller [odds ratio (OR) 44.14, 95% confidence interval (95% CI) 11.44-221.67] and flat morphology (OR 7.78, 95% CI 1.79-36.25) were significant factors that were associated with false-negative cases on PET/CT. CONCLUSION: The sensitivity of PET/CT for detecting colorectal lesions is acceptable, showing size- and pathology-dependence, suggesting, for the most part, that clinically relevant lesions are detectable with PET/CT. However, when considering PET/CT for screening purposes caution must be exercised because there are cases of false-negative results. PMID- 21983931 TI - Theoretical calculations on carbocations involved in the biosynthesis of bergamotenes and related terpenes--the same and not the same. AB - Subtle differences between carbocation rearrangements leading to the pinene/camphene, ylangene/sativene and bergamotene/santalene terpenes are revealed. PMID- 21983929 TI - Comparisons of symptoms reported by elderly and non-elderly patients with GERD. AB - BACKGROUND: The characteristics of symptoms reported by elderly patients with gastroesophageal reflux disease (GERD) have not been fully investigated. We performed this study to clarify these characteristics in elderly patients with GERD. METHODS: The study subjects were 340 Japanese patients with symptoms of heartburn and/or acid regurgitation. All patients were investigated by upper gastrointestinal endoscopy, and were asked about the presence of atypical GERD symptoms, such as an epigastric burning sensation, epigastralgia, epigastric discomfort, and abdominal fullness, as well as the time of day when bothersome symptoms occurred. RESULTS: Of the 340 patients, 161 were elderly (>=65 years old) and 179 were non-elderly (age <65 years). There were 158 patients without esophageal mucosal breaks, 147 with low-grade reflux esophagitis (RE; Los Angeles classification grade A or B), and 35 with high-grade reflux esophagitis (LA grade C or D). Elderly patients with RE reported typical reflux symptoms at the same frequency as the non-elderly patients, whereas elderly patients without mucosal breaks reported typical symptoms more frequently than the non-elderly patients without mucosal breaks. Both elderly and non-elderly patients with different types of GERD reported that their symptoms occurred most frequently during the postprandial period. CONCLUSION: Elderly patients with GERD tend to show typical GERD symptoms frequently at the typical post-prandial time points in a day, irrespective of the presence of esophageal mucosal breaks. PMID- 21983932 TI - Association of hepatocyte nuclear factor 4 alpha polymorphisms with type 2 diabetes with or without metabolic syndrome in Malaysia. AB - This study investigated the association of hepatocyte nuclear factor 4 (HNF4) alpha single nucleotide polymorphisms (SNPs) with type 2 diabetes with or without metabolic syndrome in Malaysia. Nine HNF4 alpha SNPs were genotyped in 390 type 2 diabetic subjects with metabolic syndrome, 135 type 2 diabetic subjects without metabolic syndrome, and 160 control subjects. The SNPs rs4810424, rs1884613, and rs2144908 were associated with protection against type 2 diabetes without metabolic syndrome (recessive P = 0.018, OR 0.32; P = 0.004, OR 0.25; P = 0.005, OR 0.24, respectively). The 6-SNP haplotype2 CCCGTC containing the risk genotype of these SNPs was associated with higher risk for type 2 diabetes with or without metabolic syndrome (P = 0.002, OR 2.2; P = 0.004, OR 3.1). These data suggest that HNF4 alpha SNPs and haplotypes contributed to increased type 2 diabetes risk in the Malaysian population. PMID- 21983933 TI - Analysis of stromal cells in osteofibrous dysplasia and adamantinoma of long bones. AB - Adamantinoma of long bones and osteofibrous dysplasia are rare, osteolytic primary bone tumours of uncertain origin containing areas of fibrous and fibro osseous proliferation. We investigated the nature of the stromal cells in adamantinoma of long bones and osteofibrous dysplasia, and determined cellular and molecular mechanisms of osteolysis in these tumours. Cell culture, molecular (RT-PCR, western blot) and immunohistochemical studies on cases of adamantinoma of long bones and of osteofibrous dysplasia were undertaken to determine the expression of epithelial, osteoblast and osteoclast markers. Ultrastructural and immunophenotypic studies on cultured adamantinoma and osteofibrous dysplasia stromal cells showed that these cells were mainly fibroblast-like with few cells expressing epithelial markers. Osteofibrous dysplasia but not adamantinoma cells expressed alkaline phosphatase. Both osteofibrous dysplasia and adamantinoma cells expressed the ostoclastogenic factors M-CSF and RANKL. Adamantinoma and osteofibrous dysplasia cells also expressed messenger RNA for osteocalcin, osteonectin, osteopontin, osterix and collagen type 1. Adamantinoma and osteofibrous dysplasia cells cultured alone on dentine slices were not capable of lacunar resorption, but in co-cultures with monocytes induced formation of osteoclast-like cells was observered. Cultured osteofibrous dysplasia and adamantinoma stromal cells show similar ultrastructural and immunophenotypic characteristics, and differentially express osteoblast markers. Promotion of osteoclastogenesis by stromal cells may contribute to osteolysis in adamantinoma of long bones and osteofibrous dysplasia. PMID- 21983934 TI - Epithelial-mesenchymal transition in malignant mesothelioma. AB - Epithelial-mesenchymal transition is a physiopathological process by which epithelial cells acquire mesenchymal shape and properties. Malignant mesothelioma is histologically characterized by the concomitant presence of epithelioid and sarcomatoid features, the latter being associated to worse prognosis, thus suggesting a role of epithelial-mesenchymal transition in this dual phenotype. We studied 109 malignant mesotheliomas (58 epithelioid, 26 sarcomatoid, and 25 biphasic) by immunohistochemistry and qRT-PCR analysis, and demonstrated a substantial switch from epithelial markers (E-cadherin, beta-catenin, and cytokeratins 5/6) to mesenchymal markers (N-cadherin, vimentin, alpha-smooth muscle actin, Snail, Slug, Twist, ZEB1, ZEB2, S100A4, MMP2, and MMP9) through epithelioid to biphasic and sarcomatoid histotypes. In agreement with these findings, the ectopic expression of miR-205 (a repressor of ZEB1 and ZEB2 expression) in MeT-5A (mesothelial cell line), H2452 (an epithelioid malignant mesothelioma cell line) and MSTO-211H (a biphasic malignant mesothelioma cell line) not only induced a significant reduction of ZEB1 and ZEB2 and a consequent up-regulation of E-cadherin gene expression, but also inhibited migration and invasion. Moreover, miR-205 was significantly down-regulated in biphasic and sarcomatoid histotypes (qRT-PCR and in situ hybridization analyses). Collectively, our findings indicate that epithelial-mesenchymal transition has a significant part in the morphological features of malignant mesothelioma. In particular, miR-205 down-regulation correlated significantly with both a mesenchymal phenotype and a more aggressive behavior. PMID- 21983935 TI - Accumulative copy number increase of MET drives tumor development and histological progression in a subset of ovarian clear-cell adenocarcinomas. AB - Our previous study demonstrated that, among ovarian carcinomas, amplification of the MET gene and overexpression of MET specifically and commonly occur in clear cell adenocarcinoma histology. This study was conducted to address how these alterations contribute to development and progression of this highly chemoresistant form of ovarian cancer. We histologically reviewed 21 previously described MET amplification-positive clear-cell adenocarcinoma cases, and selected 11 tumors with synchronous endometriosis and 2 tumors with adjacent clear-cell adenofibroma (CCAF) components. Using double in situ hybridization and immunohistochemistry, copy number alterations of the MET gene and levels of MET protein expression were analyzed in these putative precursor lesions and the corresponding invasive carcinoma components in this selected cohort. All of the non-atypical precursor lesions analyzed (ie, non-atypical endometrioses and the benign CCAFs) were negative for MET gain. However, low-level (>=3 MET copies in >=10% and >=4 MET copies in 10-40% of tumor cells) gain of MET was detected in 4 (40%) of the 10 atypical endometrioses and 1 of the 2 borderline CCAFs. Moreover, high-level (>=4 MET copies in >=40% of tumor cells) gain of MET were detected in five (50%) of the atypical endometrioses. In 4 (31%) of the 13 cases enrolled, intratumoral heterogeneity for MET gain was documented in invasive carcinoma components, wherein all the relatively differentiated carcinoma components showed low-level gain of MET and all the corresponding poorly differentiated carcinomas showed high-level gain. The overall incidence of MET overexpression gradually increased from the precursors of non-atypical form (0%), through those of atypical form (67%) and the relatively differentiated carcinoma components (92%), to the poorly differentiated carcinoma components (100%). These results suggest that accumulative MET gene copy number alterations causing MET overexpression are associated with higher tumor grade and might drive the development and progression of the MET amplification-positive ovarian clear-cell adenocarcinoma. PMID- 21983936 TI - A nuclear grading system is a strong predictor of survival in epitheloid diffuse malignant pleural mesothelioma. AB - Epithelioid mesothelioma is the most prevalent subtype of diffuse malignant pleural mesothelioma in which only staging is prognostic for survival. In this study of epithelioid diffuse malignant pleural mesothelioma, we investigate the prognostic utility of nuclear features. The slides of 232 epithelioid diffuse malignant pleural mesothelioma patients (14 stage I, 54 stage II, 130 stage III, and 34 stage IV) from a single institution were reviewed for the following seven nuclear features: nuclear atypia, nuclear/cytoplasmic ratio, chromatin pattern, intranuclear inclusions, prominence of nucleoli, mitotic count, and atypical mitoses. MIB-1 immunohistochemistry was performed using tissue microarray, and MIB-1 labeling index was recorded as the percentage of positive tumor cells. Median overall survival of all patients was 16 months and correlated with nuclear atypia (P<0.001), chromatin pattern (P=0.031), prominence of nucleoli (P<0.001), mitotic count (P<0.001), and atypical mitoses (P<0.001) by univariate analysis. Multivariate analysis revealed nuclear atypia (P=0.012) and mitotic count (P<0.001) as independent prognostic factors, and these two factors were utilized to create a three-tier nuclear grade score. The resulting nuclear grade stratified patients into three distinct prognostic groups: grade I (n=107, median overall survival=28 months), grade II (n=91, 14 months), and grade III (n=34, 5 months). Not only was nuclear grade an independent predictor of overall survival (P<0.001), but it was also a stronger discriminator of survival than all currently available factors. Furthermore, nuclear grade was associated with time to recurrence (P=0.004) in patients who underwent complete surgical resection (n=159). MIB-1 labeling index correlated with mitotic count (P<0.001) and nuclear atypia (P=0.037) and stratified overall survival (P<0.001) and time to recurrence (P=0.048), confirming the prognostic value of the nuclear grade. Nuclear grading in epithelioid mesothelioma provides a simple, practical, and cost-effective prognostic tool that better stratifies clinical outcome and time to recurrence than currently available clinicopathologic factors. PMID- 21983937 TI - Association of microRNA-21 expression with its targets, PDCD4 and TIMP3, in pancreatic ductal adenocarcinoma. AB - Since the discovery of small non-coding RNAs, the analyses of microRNA (miRNA) expression patterns in human cancer have provided new insights into cancer biology. miRNA-21 has been suggested to be one of the miRNAs that have an important role in the development or biological behavior of a variety of malignancies, including pancreatic cancer. This study was conducted to evaluate the relationship between the expression of miRNA-21 and that of its molecular targets, programmed cell death 4 (PDCD4) and tissue inhibitor of metalloproteinase (TIMP3), in pancreatic ductal adenocarcinoma. The study included 65 pancreatic ductal adenocarcinomas and 5 normal pancreatic tissue specimens for comparison. The miRNA expression profiling of five selected pancreatic ductal adenocarcinomas and five normal pancreatic specimens was performed using a microarray platform, and was evaluated by a hierarchical clustering analysis. The miRNA most highly expressed in pancreatic ductal adenocarcinomas (ie, miRNA-21) was further assessed by quantitative real-time reverse transcription PCR (RT-PCR) assays in the 65 pancreatic ductal adenocarcinoma cases. The expression pattern of its molecular targets (eg, PDCD4 and TIMP3) in pancreatic ductal adenocarcinoma was examined immunohistochemically. In the microarray analyses, 28 miRNAs were upregulated in pancreatic ductal adenocarcinoma compared with normal pancreatic tissue, whereas 48 miRNAs were downregulated. miRNA-21 was the most significantly overexpressed miRNA in the pancreatic ductal adenocarcinomas analyzed, and was also highly expressed in 75% of the 65 pancreatic ductal adenocarcinomas examined by real time RT-PCR. High miRNA-21 expression was correlated with a worse prognosis in the pancreatic ductal adenocarcinoma patients (P=0.045). The immunohistochemical expression patterns of PDCD4 (reduced nuclear staining pattern) and TIMP3 (downregulated expression) were significantly associated with both the upregulated miR-21 expression (P<0.05) and the poor survival of the patients (P<0.001 and P=0.001, respectively). Our data suggest that an overexpression of miRNA-21 is, therefore, associated with the biological behavior of pancreatic ductal adenocarcinoma via the downregulation of the expression of tumor suppressors, PDCD4 and TIMP3, thus resulting in tumor progression and the adverse clinical course of pancreatic ductal adenocarcinoma. PMID- 21983938 TI - Predicting shifts in generalization gradients with perceptrons. AB - Perceptron models have been used extensively to model perceptual learning and the effects of discrimination training on generalization, as well as to explore natural classification mechanisms. Here, we assess the ability of existing models to account for the time course of generalization shifts that occur when individuals learn to distinguish sounds. A set of simulations demonstrates that commonly used single-layer and multilayer perceptron networks do not predict transitory shifts in generalization over the course of training but that such dynamics can be accounted for when the output functions of these networks are modified to mimic the properties of cortical tuning curves. The simulations further suggest that prudent selection of stimuli and training criteria can allow for more precise predictions of learning-related shifts in generalization gradients in behavioral experiments. In particular, the simulations predict that individuals will show maximal peak shift after different numbers of trials, that easier contrasts will lead to slower development of shifted peaks, and that whether generalization shifts persist or dissipate will depend on which stimulus dimensions individuals use to distinguish stimuli and how those dimensions are neurally encoded. PMID- 21983939 TI - The 8-plate versus physeal stapling for temporary hemiepiphyseodesis correcting genu valgum and genu varum: a retrospective analysis of thirty five patients. AB - PURPOSE: In skeletally immature patients, treatment of malalignment about the knee is possible by performing temporary hemi-epiphyseodesis. Following the well established procedure of physeal stapling, the 8-plate was introduced as a new device. The purpose of this study was to compare physeal stapling with 8-plate hemi-epiphyseodesis. We focused on evaluating deformity correction, complication rate and duration of the procedures. METHODS: We retrospectively analysed 35 patients (61 extremities, age 2.9-16.0 years) who were treated by temporary hemi epiphyseodesis about the knee for correction of genu varum or genu valgum by using Blount staples (32 extremities) or the 8-plate (29 extremities). Plain radiographs were analysed at the time of operation and at hardware removal that included measurement of mechanical axis deviation, mechanical lateral distal femoral angle and mechanical medial proximal tibial angle. Time until hardware removal, operation time and complications were recorded. RESULTS: A statistically significant improvement of all radiographic measurements could be achieved with comparable results in both groups. Complications were similar in both groups with no relevant differences in amount and severity. In the 8-plate group, however, the surgical time was significantly shorter by an average of ten minutes for implantation and 12 minutes for explantation. CONCLUSIONS: Both Blount stapling and the 8-plate technique are methods for correction of genu varum and valgum deformity in skeletally immature patients; however, a shorter operating time for implantation and explantation was noted for the 8-plate technique. PMID- 21983940 TI - Management of Vancouver B2 and B3 femoral periprosthetic fractures using a modular cementless stem without allografting. AB - PURPOSE: We reviewed our experience with the management of B2 and B3 femoral periprosthetic fractures using a distally fixed modular femoral stem in 55 patients. METHODS: All periprosthetic fractures were managed immediately after injury without using allograft; 53 hips were available for a mean follow up of 67 months. RESULTS: All fractures united, and the mean Harris hip score at the last follow up was 72. Subsidence was noted in two patients (4%) within six months postoperatively and required revision surgery. One patient developed peroneal nerve palsy. Two hips dislocated and were managed by closed reduction. CONCLUSION: In these severe cases of periprosthetic fracture, the technique reviewed here proved to be reliable. PMID- 21983941 TI - Long-term results of total knee arthroplasty following high tibial osteotomy according to Wagner. AB - PURPOSE: There is relatively little information available about the long-term results of total knee arthroplasty (TKA) following high tibial osteotomy. The aim of our study was to share our experiences and long-term results of TKA after a previous closing wedge high tibial osteotomy according to Wagner. METHODS: In a retrospective study we identified 48 consecutive patients who had undergone TKA after a previous closing wedge high tibial osteotomy according to Wagner with a follow-up of over ten years. The average duration of follow-up after the TKA was 13.3 years (min 10.0, max 15.5). X-rays were taken in two planes before TKA, one week after TKA and at the latest follow-up. Tibio-femoral alignment was measured on weightbearing long-leg anteroposterior radiographs. Radiolucent lines at the latest follow-up were documented. Functional evaluations were performed preoperatively and postoperatively (at the time of latest follow-up). RESULTS: The mean Knee Society function score increased from 63.1 points preoperatively to 90.0 points postoperatively. The mean overall Knee Society score increased from 93.2 points preoperatively to 160.8 points postoperatively. The mean average femoro-tibial angle was corrected from varus 0.8 degrees (varus 14 degrees valgus 8.0 degrees ) preoperatively to valgus 7.6 degrees (valgus 2-9 degrees ) at the last follow-up. CONCLUSIONS: The closing wedge high tibial osteotomy according to Wagner does not compromise subsequent total knee replacement and leads to good clinical and radiological results. PMID- 21983943 TI - Educating health professionals in obstetrics and gynecology regarding rapid human immunodeficiency virus (HIV) testing in labor and delivery: a local initiative. AB - Although, the Centers for Disease Control and the American College of Obstetricians and Gynecologists have advised rapid HIV testing for laboring women of unknown human immunodeficiency virus (HIV) status since 2004 to ensure that results are known prior to delivery, physicians and hospital staff have been slow to follow the recommendation. A multi-component intervention was implemented to educate physicians and hospital staff. There was low baseline knowledge (<50% correct) in the areas of HIV prevalence, use of rapid testing in the prevention of perinatal HIV transmission, and treatment. On 9 out of 14 items, participants demonstrated a >35% increase in correct responses from pre-test to 3 month post test. Baseline knowledge among obstetric health care providers about how to diagnose and treat newly diagnosed pregnant women was low. Brief exposure to an educational program yielded a marked increase in knowledge that was sustained over 3 months. Educating health professionals in obstetrics and gynecology regarding rapid human immunodeficiency virus (HIV) testing in labor and delivery: a local initiative. PMID- 21983942 TI - Claudin-1 induced sealing of blood-brain barrier tight junctions ameliorates chronic experimental autoimmune encephalomyelitis. AB - In experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), loss of the blood-brain barrier (BBB) tight junction (TJ) protein claudin-3 correlates with immune cell infiltration into the CNS and BBB leakiness. Here we show that sealing BBB TJs by ectopic tetracycline-regulated expression of the TJ protein claudin-1 in Tie-2 tTA//TRE-claudin-1 double transgenic C57BL/6 mice had no influence on immune cell trafficking across the BBB during EAE and furthermore did not influence the onset and severity of the first clinical disease episode. However, expression of claudin-1 did significantly reduce BBB leakiness for both blood borne tracers and endogenous plasma proteins specifically around vessels expressing claudin-1. In addition, mice expressing claudin-1 exhibited a reduced disease burden during the chronic phase of EAE as compared to control littermates. Our study identifies BBB TJs as the critical structure regulating BBB permeability but not immune cell trafficking into CNS during EAE, and indicates BBB dysfunction is a potential key event contributing to disease burden in the chronic phase of EAE. Our observations suggest that stabilizing BBB barrier function by therapeutic targeting of TJs may be beneficial in treating MS, especially when anti inflammatory treatments have failed. PMID- 21983944 TI - Community effects on pregnancy intention among cohabiting women in the Philippines: implications for maternal and child health. AB - Unintended pregnancy impacts both maternal and child health. International studies continue to emphasize the importance of reproductive health in the context of community. Only a few researchers have explored the impact of community factors on pregnancy intention using population-based surveys. This issue is of particular importance for women of low socioeconomic status in developing countries, where unintended fertility rates remain relatively high. Using the 1998 (n = 6,849) and 2003 (n = 6,773) Demographic and Health Surveys in the Philippines, we employed multilevel logistic models to explore whether community factors are associated with pregnancy intention among these women. The results showed community social capital, comprised of community-related variables, significantly predicted women's pregnancy intention, even after controlling for women's socioeconomic status, individual background factors, and spousal characteristics. The relationship between pregnancy intention and selected variables associated with community social capital, however, was not consistent across the two surveys. Community context, in general, has a significant influence on women's pregnancy intention. Specific components of the community context vary in their associations with pregnancy intention over time. In addition, differences in pregnancy intention may explain individual-level social disparities between communities. These findings suggest population health policies designed to promote maternal and child health must be context-specific. PMID- 21983946 TI - Photosensitized water oxidation by use of a bioinspired manganese catalyst. PMID- 21983945 TI - Natural killer inhibitory receptor expression associated with treatment failure and interleukin-28B genotype in patients with chronic hepatitis C. AB - Natural killer (NK) cells constitute a first line of defense against viral infections; their function is governed by the integration of signals from multiple activating and inhibitory surface receptors. We hypothesized that because NKs become rapidly activated by cytokines, response to anti-hepatitis C virus (HCV) therapy would be predicted by the phenotype and function of NKs. We used a cohort of 101 patients (55 African, 46 Caucasian-American) who received pegylated-interferon (IFN) and ribavirin for 48 weeks. Multiparameter FACS analysis was used to examine relative expression of 14 different inhibitory/activating receptors. Interleukin (IL)-28B genotyping (rs12979860) was also performed. Pretreatment levels of inhibitory receptors CD158a, CD158b, and CD158e were higher in patients who demonstrated poor viral decline within the first 28 days of therapy. Higher expression levels of inhibitory receptors NKG2A, CD158b, and CD158e were demonstrable in patients who failed to achieve sustained virologic response (SVR). Patients carrying the IL-28B T allele had higher NKG2A expression on effector NKs. We created a mathematical regression model incorporating race, viral level, and two inhibitory receptors. The area-under-the curve was 0.88, which is highly predictive of SVR. Moreover, the model performed complementarily with IL-28B across the CC, CT, and TT genotypes. Purified NKG2A(neg) NKs treated with pegylated-IFN-alpha for 4 hours demonstrated higher levels of IFN-gamma-inducible protein-10 (IP-10) and tumor necrosis factor related apoptosis-inducing ligand (TRAIL) compared with their NKG2A(pos) counterparts. CONCLUSIONS: These results provide novel insights into the associations of NK phenotype with IL-28B genotype and gene expression patterns, as well as the role of NKs in mediating IFN-induced viral clearance of chronic HCV infection. PMID- 21983947 TI - Nonpolar organic compounds in fine particles: quantification by thermal desorption-GC/MS and evidence for their significant oxidation in ambient aerosols in Hong Kong. AB - Nonpolar organic compounds (NPOCs) in ambient particulate matter (PM) commonly include n-alkanes, branched alkanes, hopanes and steranes, and polycyclic aromatic hydrocarbons (PAHs). The recent development of thermal desorption-gas chromatography/mass spectrometry (TD-GC/MS) has greatly reduced time and labor in their quantification by eliminating the laborious solvent extraction and sample concentration steps in the traditional approach that relies on solvent extraction. The simplicity of the TD-GCMS methods has afforded us concentration data of NPOCs in more than 90 aerosol samples in two aerosol field studies and 20 vehicular emissions-dominated source samples in Hong Kong over the past few years. In this work, we examine the interspecies relationships between select NPOCs and their concentration ratios to elemental carbon (EC) among the ambient samples and among the source samples. Our analysis indicates that hopanes were mainly from vehicular emissions and they were significantly oxidized in ambient PM. The hopane/EC ratio in ambient samples was on average less than half of the ratio in vehicular emissions-dominated source samples. This highlights the necessity in considering oxidation loss in applying organic tracer data in source apportionment studies. Select PAH/EC ratio-ratio plots reveal that PAHs had diverse sources and vehicular emissions were unlikely a dominant source for PAHs in Hong Kong. Biomass burning and other regional sources likely dominated ambient PAHs in Hong Kong. PMID- 21983948 TI - A sprayable hyaluronate/carboxymethylcellulose adhesion barrier exhibits regional adhesion reduction efficacy and does not impair intestinal healing. AB - BACKGROUND: While bioresorbable solid barriers such as Seprafilm(r) prevent adhesions, their efficacy is limited to sites of application. The aim of this study was to assess the effectiveness of the sprayable adhesion barrier Sepraspray(r) in preventing adhesions to sites of direct application and to remote sites. METHODS: Intraabdominal adhesions were induced in 30 rats by creating three ischemic buttons on each side of a midline incision. To assess efficacy, Sepraspray (5 mg/button) or Seprafilm (1 cm(2)/button) was applied over three buttons on one side of the peritoneum. Operated control animals received no treatment. On day 7, adhesions were scored as percent of buttons with adhesions. To assess safety, 81 rats underwent a colonic transection repaired with an end-to end anastomosis. Both barriers were applied circumferentially to anastomoses. Controls received no product. The integrity of healing anastomosed colonic wounds was assessed by burst pressure and tensile strength at days 3, 5, and 7 postoperatively. RESULTS: The direct application of both Sepraspray and Seprafilm significantly (p < 0.001) reduced adhesion formation compared to controls. While Seprafilm had no remote effect on adhesion formation, Sepraspray significantly (p < 0.001) reduced adhesion formation to contralateral ischemic buttons. Neither barrier affected anastomotic integrity at any time point. CONCLUSIONS: Sepraspray has widespread efficacy throughout the peritoneum in reducing adhesions without compromising intestinal healing. Furthermore, this sprayable alternative offers the potential for easier intraabdominal application. PMID- 21983949 TI - Torsion of the gallbladder. AB - INTRODUCTION: A 77-year-old woman was seen with progressive abdominal pain. CASES: A CT scan was made and showed a large gallbladder extending into the right lower abdomen. Ultrasound was performed but demonstrated no gallstones. Laparoscopy showed a tordated, necrotic gallbladder that was attached to the liver only by the cystic artery and cystic duct. Cholecystectomy was performed. CONCLUSIONS: Torsion of the gallbladder is a rare but clinically important condition in which the diagnosis seldom is made preoperatively. In radiological and clinical signs of cholecystitis without gallstones, this condition should be considered. PMID- 21983952 TI - Raynaud's phenomenon. PMID- 21983950 TI - Innate immune environment in ileal pouch mucosa: alpha5 defensin up-regulation as predictor of chronic/relapsing pouchitis. AB - Defensins are small cationic peptides with antibacterial activity expressed in Paneth cells (alpha-defensins) or generally in intestinal epithelial cells (beta defensins) that have a profound effect on gut microbiota. Chronic pouchitis, which occurs in 5% of patients after restorative proctocolectomy and can cause pouch failure, is associated to a significant increase of Clostridiaceae spp. The aim of this study was to gain further insight in the pathogenesis of pouch dysbiosis by exploring defensin expression. Thirty-two consecutive patients coming for follow-up endoscopy were recruited. On pouch biopsies, we cultured bacteria adherent to the mucosa and determined alpha- and beta-defensins and toll like receptor-4 and -2 mRNA by quantitative real-time RT-PCR. Serum and mucosal levels of IL-1beta, IL-6 and TNF-alpha were measured with immunometric assays. Faecal lactoferrin was analysed by quantitative ELISA. After a median follow-up of 23 (IQR 20-24) months, the patients were contacted for a reassessment of current and past disease activity. During the follow-up, chronic/relapsing pouchitis was diagnosed in six patients. The mucosal level of alpha-5 and alpha-6 defensins correlated with chronic/relapsing pouchitis onset (tau = 0.30, p = 0.034 and tau = 0.28, p = 0.053, respectively). High levels of alpha-5 defensin resulted to be predictive of chronic/relapsing pouchitis [AUC = 74% (95% CI = 53 89%), p = 0.052]. Patients with high levels of alpha-5 and alpha-6 defensins had earlier pouchitis relapses (p = 0.009 and p = 0.034, respectively). High levels of alpha-5 defensin were associated to a significant risk of chronic/relapsing pouchitis [OR = 10.6 (95% CI = 1.2-97.6), p = 0.027]. At multivariate analysis, the mucosal levels of alpha-5 defensin and the number of CFU of mucosa-associated Clostridiaceae spp resulted to be independent predictors of chronic/relapsing pouchitis [beta = 0.46 (0.18), p = 0.024 and beta = 0.44 (0.18), p = 0.027, respectively]. In conclusion, chronic/relapsing pouchitis is associated to increased expression of mucosal HD-5 and to increased antimicrobial activity against Escherichia coli. In patients with chronic/relapsing pouchitis, HD-5 and TLR-4 over-expression is likely to create a hostile environment against Enterobacteriaceae, thus favouring Clostridiaceae spp by decreasing competing bacteria families. PMID- 21983953 TI - Double-chambered right ventricle: an uncommon congenital heart disease. Case report and literature review. AB - A double-chambered right ventricle (DCRV) is a rare congenital heart disease and an uncommon cause of congestive cardiac failure. An anomalous muscle band divides the right ventricle into two cavities, causing variable degrees of obstruction. Echocardiography is considered a useful method for the diagnosis of this pathology, especially in children. An eight-year-old patient with a small ventricular septal defect (VSD) and double-chambered right ventricle presented with a history of palpitations, easy fatigability and recurrent fever. On presentation, she had features of congestive cardiac failure. A complete diagnosis was initially missed with transthoracic two-dimensional (2-D) echocardiography but later obtained based on transthoracic 2-D echocardiography with Doppler facility. This was confirmed with cardiac catheterisation. The patient was referred for surgical correction, which was successful. Due to the rarity of this condition and the consequences of missing the diagnosis, we present this case in order to highlight the rarity of this congenital heart disease in childhood. PMID- 21983954 TI - South Africa's PACE is a winner of Boehringer-Ingelheim's international atrial fibrillation awareness programme. PMID- 21983955 TI - Medtronic news from European Society of Cardiology congress, Paris, September 2011. PMID- 21983956 TI - Expanded coverage for warfarin patients in the USA monitoring clotting time at home. PMID- 21983957 TI - Namibia becomes first country in Africa to launch dabigatran etexilate for atrial fibrillation. PMID- 21983958 TI - New insights and results from the RE-LY trial. PMID- 21983959 TI - European Society of Cardiology congress 2011. PMID- 21983960 TI - Proteomic and phosphoproteomic comparison of human ES and iPS cells. AB - Combining high-mass-accuracy mass spectrometry, isobaric tagging and software for multiplexed, large-scale protein quantification, we report deep proteomic coverage of four human embryonic stem cell and four induced pluripotent stem cell lines in biological triplicate. This 24-sample comparison resulted in a very large set of identified proteins and phosphorylation sites in pluripotent cells. The statistical analysis afforded by our approach revealed subtle but reproducible differences in protein expression and protein phosphorylation between embryonic stem cells and induced pluripotent cells. Merging these results with RNA-seq analysis data, we found functionally related differences across each tier of regulation. We also introduce the Stem Cell-Omics Repository (SCOR), a resource to collate and display quantitative information across multiple planes of measurement, including mRNA, protein and post-translational modifications. PMID- 21983961 TI - A role for the PKC signaling system in the pathophysiology and treatment of mood disorders: involvement of a functional imbalance? AB - Mood disorders, such as bipolar and major depressive disorders, are frequent, severe, and often disabling neuropsychiatric diseases affecting millions of individuals worldwide. Available mood stabilizers and antidepressants remain unsatisfactory because of their delayed and partial therapeutic efficacy. Therefore, the development of targeted therapies, working more rapidly and being fully effective, is urgently needed. In this context, the protein kinase C (PKC) signaling system, which regulates multiple neuronal processes implicated in mood regulation, can constitute a novel therapeutic target. This paper reviews the currently available knowledge regarding the role of the PKC signaling pathway in the pathophysiology of mood disorders and the therapeutic potential of PKC modulators. Current antidepressants and mood stabilizers have been shown to modulate the PKC pathway, and the inhibition of this intracellular signaling cascade results in antimanic-like properties in animal models. Disrupted PKC activity has been found both in postmortem brains and platelet from patients with mood disorders. Finally, the PKC inhibitor tamoxifen has recently demonstrated potent antimanic properties in several clinical trials. Overall, emerging data from preclinical and clinical research suggest an imbalance of the PKC signaling system in mood disorders. Thus, PKC may be a critical molecular target for the development of innovative therapeutics. PMID- 21983962 TI - Macrophage skewing by Phd2 haplodeficiency prevents ischaemia by inducing arteriogenesis. AB - PHD2 serves as an oxygen sensor that rescues blood supply by regulating vessel formation and shape in case of oxygen shortage. However, it is unknown whether PHD2 can influence arteriogenesis. Here we studied the role of PHD2 in collateral artery growth by using hindlimb ischaemia as a model, a process that compensates for the lack of blood flow in case of major arterial occlusion. We show that Phd2 (also known as Egln1) haplodeficient (Phd2(+/-)) mice displayed preformed collateral arteries that preserved limb perfusion and prevented tissue necrosis in ischaemia. Improved arteriogenesis in Phd2(+/-) mice was due to an expansion of tissue-resident, M2-like macrophages and their increased release of arteriogenic factors, leading to enhanced smooth muscle cell (SMC) recruitment and growth. Both chronic and acute deletion of one Phd2 allele in macrophages was sufficient to skew their polarization towards a pro-arteriogenic phenotype. Mechanistically, collateral vessel preconditioning relied on the activation of canonical NF-kappaB pathway in Phd2(+/-) macrophages. These results unravel how PHD2 regulates arteriogenesis and artery homeostasis by controlling a specific differentiation state in macrophages and suggest new treatment options for ischaemic disorders. PMID- 21983963 TI - Distinct stem cells contribute to mammary gland development and maintenance. AB - The mammary epithelium is composed of several cell lineages including luminal, alveolar and myoepithelial cells. Transplantation studies have suggested that the mammary epithelium is maintained by the presence of multipotent mammary stem cells. To define the cellular hierarchy of the mammary gland during physiological conditions, we performed genetic lineage-tracing experiments and clonal analysis of the mouse mammary gland during development, adulthood and pregnancy. We found that in postnatal unperturbed mammary gland, both luminal and myoepithelial lineages contain long-lived unipotent stem cells that display extensive renewing capacities, as demonstrated by their ability to clonally expand during morphogenesis and adult life as well as undergo massive expansion during several cycles of pregnancy. The demonstration that the mammary gland contains different types of long-lived stem cells has profound implications for our understanding of mammary gland physiology and will be instrumental in unravelling the cells at the origin of breast cancers. PMID- 21983964 TI - Feedback from rhodopsin controls rhodopsin exclusion in Drosophila photoreceptors. AB - Sensory systems with high discriminatory power use neurons that express only one of several alternative sensory receptor proteins. This exclusive receptor gene expression restricts the sensitivity spectrum of neurons and is coordinated with the choice of their synaptic targets. However, little is known about how it is maintained throughout the life of a neuron. Here we show that the green-light sensing receptor rhodopsin 6 (Rh6) acts to exclude an alternative blue-sensitive rhodopsin 5 (Rh5) from a subset of Drosophila R8 photoreceptor neurons. Loss of Rh6 leads to a gradual expansion of Rh5 expression into all R8 photoreceptors of the ageing adult retina. The Rh6 feedback signal results in repression of the rh5 promoter and can be mimicked by other Drosophila rhodopsins; it is partly dependent on activation of rhodopsin by light, and relies on G(alphaq) activity, but not on the subsequent steps of the phototransduction cascade. Our observations reveal a thus far unappreciated spectral plasticity of R8 photoreceptors, and identify rhodopsin feedback as an exclusion mechanism. PMID- 21983965 TI - Active-site remodelling in the bifunctional fructose-1,6-bisphosphate aldolase/phosphatase. AB - Fructose-1,6-bisphosphate (FBP) aldolase/phosphatase is a bifunctional, thermostable enzyme that catalyses two subsequent steps in gluconeogenesis in most archaea and in deeply branching bacterial lineages. It mediates the aldol condensation of heat-labile dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (GAP) to FBP, as well as the subsequent, irreversible hydrolysis of the product to yield the stable fructose-6-phosphate (F6P) and inorganic phosphate; no reaction intermediates are released. Here we present a series of structural snapshots of the reaction that reveal a substantial remodelling of the active site through the movement of loop regions that create different catalytic functionalities at the same location. We have solved the three-dimensional structures of FBP aldolase/phosphatase from thermophilic Thermoproteus neutrophilus in a ligand-free state as well as in complex with the substrates DHAP and FBP and the product F6P to resolutions up to 1.3 A. In conjunction with mutagenesis data, this pinpoints the residues required for the two reaction steps and shows that the sequential binding of additional Mg(2+) cations reversibly facilitates the reaction. FBP aldolase/phosphatase is an ancestral gluconeogenic enzyme optimized for high ambient temperatures, and our work resolves how consecutive structural rearrangements reorganize the catalytic centre of the protein to carry out two canonical reactions in a very non-canonical type of bifunctionality. PMID- 21983966 TI - Structural basis for the bifunctionality of fructose-1,6-bisphosphate aldolase/phosphatase. AB - Enzymes catalyse specific reactions and are essential for maintaining life. Although some are referred to as being bifunctional, they consist of either two distinct catalytic domains or a single domain that displays promiscuous substrate specificity. Thus, one enzyme active site is generally responsible for one biochemical reaction. In contrast to this conventional concept, archaeal fructose 1,6-bisphosphate (FBP) aldolase/phosphatase (FBPA/P) consists of a single catalytic domain, but catalyses two chemically distinct reactions of gluconeogenesis: (1) the reversible aldol condensation of dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GA3P) to FBP; (2) the dephosphorylation of FBP to fructose-6-phosphate (F6P). Thus, FBPA/P is fundamentally different from ordinary enzymes whose active sites are responsible for a specific reaction. However, the molecular mechanism by which FBPA/P achieves its unusual bifunctionality remains unknown. Here we report the crystal structure of FBPA/P at 1.5-A resolution in the aldolase form, where a critical lysine residue forms a Schiff base with DHAP. A structural comparison of the aldolase form with a previously determined phosphatase form revealed a dramatic conformational change in the active site, demonstrating that FBPA/P metamorphoses its active-site architecture to exhibit dual activities. Thus, our findings expand the conventional concept that one enzyme catalyses one biochemical reaction. PMID- 21983967 TI - The effect of intrathecal mu, delta, kappa, and alpha-2 agonists on thermal hyperalgesia induced by mild burn on hind paw in rats. AB - PURPOSE: Mild cutaneous thermal injury, leading to a first-degree burn, induces a sensation of burning pain and enhances the pain sensitivity of the skin. Opioid and alpha(2) receptor agonists are commonly used to reduce such hyperalgesia. We investigated conditions that induced adequate thermal hyperalgesia in rats and compared the effects of MU, delta, kappa, and alpha(2) receptors at the level of the spinal cord in this model. METHODS: A total of 149 male Sprague-Dawley rats were submitted to this study. A first-degree burn injury was induced in the hind paw by contact with a hot plate. The nociceptive threshold was determined by measuring the time from the application of a light beam to the hind paw to the withdrawal response (paw withdrawal latency, PWL). Various hot-plate exposure times and light beam intensities were tested to determine the conditions that induced adequate hyperalgesia. We also tested the effects of intrathecal morphine (MU agonist), DPDPE ([D-Pen2, D-Pen5] enkephalin, a delta agonist), U50488H (trans(+)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]-benzacetamide methane sulfonate salt, a kappa agonist), and ST-91 (2-[2,6-diethyl-phenylamino] 2-imidazoline, an alpha(2) agonist) on PWL. RESULTS: A first-degree burn was induced by contact with the hot plate for 45 s. Using current of 5.0 A, PWL was reduced by 40% from baseline. Intrathecally administered morphine, DPDPE, and ST 91, but not U50488H, showed dose-dependent antinociceptive effects in both injured and normal paws. CONCLUSIONS: Based on these findings, we could find adequate conditions for thermal hyperalgesia model. In this experimental model, MU, delta, and alpha(2) receptor agonists produced antinociceptive effects at the level of the spinal cord, but the kappa receptor agonist did not. PMID- 21983968 TI - Lung injury induced by the pulmonary instillation of povidone-iodine in rats. AB - PURPOSE: Povidone-iodine (polyvinylpyrrolidone iodine, PI), which is commonly used as a pre- and postoperative oral antiseptic, has been reported to cause pneumonia secondary to its pulmonary aspiration. Because no studies have yet investigated the underlying mechanisms of PI-induced pneumonia, we conducted an animal study to analyze the effect of PI on the lung following its pulmonary instillation. METHODS: The lungs of 61 male Sprague-Dawley rats (150-250 g) were instilled with varying volumes of either phosphate-buffered saline or PI solutions varying in strength from 0.01% to 10%. The lungs were harvested from the rats 1 h or 1, 3, 5, 7, 14, or 21 days after instillation for radiologic examination, macroscopic and light and scanning electron microscopic assessment, and an assessment of pulmonary toxicity using an MTT-based cytotoxicity assay. RESULTS: Macroscopically, atelectasis was the primary pulmonary lesion after PI instillation. The primary light and scanning electron microscopic findings were an initial inflammatory phase with edema, alveolar rupture, and leukocyte infiltration into the pulmonary interstitium, which progressed into a phase of lung parenchyma loss, and then resolved itself with scar tissue formation. Lung tissue viability following 1-day exposure to 0.01%, 0.1%, 1%, or 5% PI progressively decreased in a significant dose-dependent manner. CONCLUSIONS: PI aspiration can cause lung injury, including pulmonary fibrosis. PMID- 21983970 TI - Transient expression and activity of human DNA polymerase iota in loach embryos. AB - Human DNA polymerase iota (Pol iota) is a Y-family DNA polymerase with unusual biochemical properties and not fully understood functions. Pol iota preferentially incorporates dGTP opposite template thymine. This property can be used to monitor Pol iota activity in the presence of other DNA polymerases, e.g. in cell extracts of tissues and tumors. We have now confirmed the specificity and sensitivity of the method of Pol iota activity detection in cell extracts using an animal model of loach Misgurnus fossilis embryos transiently expressing human Pol iota. The overexpression of Pol iota was shown to be accompanied by an increase in abnormalities in development and the frequency of pycnotic nuclei in fish embryos. Further analysis of fish embryos with constitutive or regulated Pol iota expression may provide insights into Pol iota functions in vertebrate animals. PMID- 21983971 TI - Viability of free and encapsulated Escherichia coli overexpressing cyclopentanone monooxygenase monitored during model Baeyer-Villiger biooxidation by confocal laser scanning microscopy. AB - Baeyer-Villiger biooxidation of 4-methylcyclohexanone-5-methyloxepane-2-one catalysed by recombinant Escherichia coli overexpressing cyclopentanone monooxygenase encapsulated in polyelectrolyte complex capsules was used to investigate effect of substrate conversion on the viability of cells. Confocal laser scanning microscopy (CLSM) was used to assess cell viability using propidium iodide fluorescence marker for necrosis, and flavin autofluorescence to identify living bacteria. Viability of encapsulated cells decreased with increasing substrate concentration from 99 +/- 1 to 83 +/- 4%, while substrate conversions from decreased 100 to 6 +/- 1%. Storage stabilization of encapsulated cells was observed by increased substrate conversion form 68 +/- 2 to 96 +/- 3%. Measurements by CLSM with standard deviations up to 5% may be regarded as powerful tool for recombinant cell viability determination during Baeyer-Villiger biooxidations. PMID- 21983972 TI - Fluorescent proteins in microbial biotechnology--new proteins and new applications. AB - The recent advances over the past 5 years in the utilisation of fluorescent proteins in microbial biotechnology applications, including recombinant protein production, food processing, and environmental biotechnology, are reviewed. We highlight possible areas where fluorescent proteins currently used in other bioscience disciplines could be adapted for use in biotechnological applications and also outline novel uses for recently developed fluorescent proteins. PMID- 21983973 TI - Photosystem I from plants as a bacterial cytochrome P450 surrogate electron donor: terminal hydroxylation of branched hydrocarbon chains. AB - The ability of cytochrome P450 enzymes to catalyze highly regio- and stereospecific hydroxylations makes them attractive alternatives to approaches based on chemical synthesis but they require expensive cofactors, e.g. NAD(P)H, which limits their commercial potential. Ferredoxin (Fdx) is a multifunctional electron carrier that in plants accepts electrons from photosystem I (PSI) and facilitates photoreduction of NADP(+) to NADPH mediated by ferredoxin-NAD(P)H oxidoreductase (FdR). In bacteria, the electron flow is reversed and Fdx accepts electrons from NADPH via FdR and serves as the direct electron donor to bacterial P450s. By combining the two systems, we demonstrate that irradiation of PSI can drive the activity of a bacterial P450, CYP124 from Mycobacterium tuberculosis. The substitution of the costly cofactor NADPH with sunlight illustrates the potential of the light-driven hydroxylation system for biotechnology applications. PMID- 21983974 TI - Redox profile in liver of Leporinus macrocephalus exposed to different dissolved oxygen levels. AB - Aquatic organisms are continuously exposed to environmental variations, which can lead to physiological and biochemical alterations. Leporinus macrocephalus, known as piavucu, is a migratory species that may be exposed to variations in dissolved oxygen levels. Studies evaluating oxidative changes undergone by this species in these conditions are scarce. Therefore, this investigation aimed at evaluating oxidative alterations in L. macrocephalus exposed to different oxygen levels for 96 h: 6.12 +/- 0.18, 3.99 +/- 0.17, 3.22 +/- 0.17, 2.47 +/- 0.30 and 0.710 +/- 0.07 mg L(-1). At the end of the experimental period, fish were euthanized and livers used to determine lipid hydroperoxides, thiobarbituric acid reactive substances, catalase, glutathione-S-transferase, superoxide dismutase and thiol groups, which are an indirect measure of reduced glutathione. Results indicated a decrease in the studied parameters in hypoxic situations, suggesting a possible metabolic depression. PMID- 21983975 TI - Navigation in minimally invasive unicompartmental knee arthroplasty has no advantage in comparison to a conventional minimally invasive implantation. AB - INTRODUCTION: Minimally invasive implantation of unicompartmental knee prostheses can shorten rehabilitation time and lead to better functional results than conventional implantation. Exact positioning of the implant should be achieved, as this is a factor for the long-term survival of the prosthesis, although malpositioning can result due to the poor intraoperative view when using the minimally invasive approach. Navigation of the unicompartmental prosthesis could lead to a better implant positioning without losing the advantages of a minimally invasive approach. MATERIALS AND METHODS: The same unicondylar knee prosthesis was implanted in a total of 40 patients, of whom 20 were implanted using navigation (kinematic navigation) and 20 using a conventional technique. The operating time was assessed in both groups. The orientation of the tibial and femoral implants was assessed radiologically postoperatively. We analysed these results according to the optimal positioning range proposed by the manufacturer. Furthermore, we examined the clinical results with the knee society score (KSS). RESULTS: A good positioning of the prosthesis was observed in both techniques with only 11% of the radiologic measurements out of the proposed optimal range in each group. The operating time was significantly longer in the navigation group (17 min). The KSS did not differ between both groups at a follow-up of 16 resp. 18 months (navigated group: 184 points, conventional group: 178 points). CONCLUSIONS: Navigation did not lead to a better positioning of the prosthesis than the conventional method and the operating time was longer. The clinical results were similar in both groups. The navigation may be a useful help for surgeons performing less unicompartmental knee arthroplasty using a minimally invasive approach. PMID- 21983976 TI - Transfer of graduating residents' continuity practices. PMID- 21983977 TI - Direct MU-flow injection isotope dilution ICP-MS for the determination of heavy metals in oil samples. AB - The determination of trace elements in oil samples and their products is of high interest as their presence significantly affects refinery processes and the environment by possible impact of their combustion products. In this context, inductively coupled plasma mass spectrometry (ICP-MS) plays an important role due to its outstanding analytical properties in the quantification of trace elements. In this work, we present the accurate and precise determination of selected heavy metals in oil samples by making use of the combination of MU-flow direct injection and isotope dilution ICP-MS (ICP-IDMS). Spike solutions of (62)Ni, (97)Mo, (117)Sn and (206)Pb were prepared in an organic solvent, mixed directly with the diluted oil samples and tested to be fit for purpose for the intended ID approach. The analysis of real samples revealed strong matrix effects affecting the ICP-MS sensitivity, but not the isotope ratio measurements, so that accurate results are obtained by ICP-IDMS. Typical relative standard deviations were about 15% for peak area and peak height measurements, whereas the isotope ratios were not significantly affected (RSD < 2%). The developed method was validated by the analysis of a metallo-organic multi-element standard (SCP-21, typically applied as a calibration standard) and the standard reference material SRM1084a (wear metals in lubricating oil). The obtained results were in excellent agreement with the certified values (recoveries between 98% and 102%), so the proposed methodology of combining MU-flow direct injection and ICP-IDMS can be regarded as a new tool for the matrix-independent, multi-element and reliable determination of trace elements in oil and related organic liquids. PMID- 21983978 TI - Advantages of a programmed temperature vaporizer inlet and parallel factor analysis in the determination of triazines in the presence of non-intentionally added substances by gas chromatography. AB - Non-intentionally added substances (NIASs) are usually detected by acquiring mass spectra in full scan mode and then identifying the compounds corresponding to the unexpected peaks. High-resolution mass spectrometry detectors are frequently used, but this does not solve the problem that an NIAS can contribute to the abundance at m/z ratios that correspond to the fragmentation of other molecules. This problem leads to false negatives when identifying compounds, even in target analysis when the maximum permitted tolerances for relative ion abundances (SANCO/10684/2009) are taken into account. In this work, the introduction of different volumes of a test sample onto a GC/MS system that has a programmed temperature vaporizer inlet and is operating in full scan mode provides a data tensor. The proposed approach consists of considering the structure of the matrix of abundances of K m/z ratios acquired at J elution times for each chromatographic peak. Upon concatenating I of such matrices, a three-way tensor X is obtained, which is then decomposed using parallel factor analysis into as many factors as there are substances coeluting, thus providing the mass spectrum and the chromatographic profile for each of them. If the amount of an analyte changes significantly during the I injections, then it can be unequivocally identified. This procedure thus identifies coeluting NIASs, provides information about their mass spectra, and guarantees the identification and quantification of target compounds. In this work, it is used to determine five triazines in the presence of NIASs which match some of the m/z ratios of the triazines and coelute with them. Decision limits (CCalpha) of between 7.5 and 25.0 MUg L(-1) were obtained. PMID- 21983979 TI - Multi-residue determination of pesticides in tropical fruits using liquid chromatography/tandem mass spectrometry. AB - Monitoring pesticide residues in tropical fruits is of great interest for many countries, e.g., from South America, that base an important part of their economy on the exportation of these products. In this work, a LC-MS/MS multi-residue method using a triple quadrupole analyzer has been developed for around 30 pesticides in seven Colombian tropical fruits of high commercial value for domestic and international markets (uchuva, tamarillo, granadilla, gulupa, maracuya, papaya, and pithaya). After sample extraction with acetonitrile, an aliquot of the extract was diluted with water and directly injected into the HPLC MS/MS system (electrospray interface) without any cleanup step. The formation of sodium adducts-of poor fragmentation-was minimized using 0.1% formic acid in the mobile phase, which favored the formation of the protonated molecule. However, the addition of ammonium acetate made the formation of the ammonium adducts in some particular cases possible, avoiding the presence of the sodium adducts. The highest sensitivity was observed in positive electrospray ionization for the wide majority of pesticides, with a few exceptions for acidic compounds that gave better response in the negative mode (e.g., 2,4-D, fluazinan). Thus, simultaneous acquisition on the positive/negative mode was applied. Two MS/MS transitions were acquired for each compound to ensure a reliable quantification and identification of the compounds detected in samples, although for malathion a third transition was acquired due to the presence of interfering isobaric compounds in the sample extracts. A detailed study of matrix effects was made by a comparison of standards in solvent and in matrix. Both ionization suppression and ionization enhancement were observed depending on the analyte/matrix combination tested. Correction of matrix effects was made by the application of calibration in matrix. Three matrices were selected (uchuva, maracuya, gulupa) to perform matrix calibration in the analysis of all seven fruit varieties studied. The method was validated by recovery experiments in samples spiked at two levels (0.05 and 0.5 mg/kg). The data were satisfactory for the wide majority of analyte/matrix combinations, with most recoveries between 70% and 110% and the RSD below 15%. Several samples collected from the market were finally analyzed. Positive findings were confirmed by evaluating the experimental Q/q ratios and retention times, and comparing them with those of reference standards. PMID- 21983980 TI - Quantitative profiling of tryptophan metabolites in serum, urine, and cell culture supernatants by liquid chromatography-tandem mass spectrometry. AB - A sensitive, selective, and comprehensive method for the quantitative determination of tryptophan and 18 of its key metabolites in serum, urine, and cell culture supernatants was developed. The analytes were separated on a C18 silica column by reversed-phase liquid chromatography and detected by electrospray ionization tandem mass spectrometry in positive ion multiple reaction monitoring (MRM) mode, except for indoxyl sulfate which was measured in negative ion MRM mode in a separate run. The limits of detection and lower limits of quantification were in the range of 0.1-50 and 0.5-100 nM, respectively. Fully (13)C isotope-labeled and deuterated internal standards were used to achieve accurate quantification. The applicability of the method to analyze serum, urine, and cell culture supernatants was demonstrated by recovery experiments and the evaluation of matrix effects. Precision for the analysis of serum, urine, and cell culture supernatants ranged between 1.3% and 16.0%, 1.5% and 13.5%, and 1.0% and 17.4%, respectively. The method was applied to analyze changes in tryptophan metabolism in cell culture supernatants from IFN-gamma-treated monocytes and immature or mature dendritic cells. PMID- 21983981 TI - First field application of a thermal desorption resonance-enhanced multiphoton ionisation single particle time-of-flight mass spectrometer for the on-line detection of particle-bound polycyclic aromatic hydrocarbons. AB - The on-line analysis of single aerosol particles with mass spectrometrical methods is an important tool for the investigation of aerosols. Often, a single laser pulse is used for one-step laser desorption/ionisation of aerosol particles. Resulting ions are detected with time-of-flight mass spectrometry. With this method, the detection of inorganic compounds is possible. The detection of more fragile organic compounds and carbon clusters can be accomplished by separating the desorption and the ionisation in two steps, e.g. by using two laser pulses. A further method is, using a heated metal surface for thermal desorption of aerosol particles. If an ultraviolet laser is used for ionisation, a selective ionisation of polycyclic aromatic hydrocarbons (PAH) and alkylated PAH is possible via a resonance-enhanced multiphoton-ionisation process. Laser velocimetry allows individual laser triggering for single particles and additionally delivers information on aerodynamic particle diameters. It was shown that particles deriving from different combustion sources can be differentiated according to their PAH patterns. For example, retene, a C(4)-alkylated phenanthrene derivative, is a marker for the combustion of coniferous wood. In this paper, the first field application of a thermal desorption resonance enhanced multiphoton-ionisation single particle time-of-flight mass spectrometer during a measurement campaign in Augsburg, Germany in winter 2010 is presented. Larger PAH-containing particles (i.e. with aerodynamic diameters larger than 1 MUm), which are suspected to be originated by re-suspension processes of agglomerated material, were in the focus of the investigation. Due to the low concentration of these particles, an on-line virtual impactor enrichment system was used. The detection of particle-bound PAH in ambient particles in this larger size region was possible and in addition, retene could be detected on several particles, which allows to identify wood combustion as generic source of these particles. The observed diurnal distribution of these larger particles, however, support the origin by traffic induced re-suspension of sedimented/agglomerated material. PMID- 21983982 TI - Fluoridized iron phosphate as a novel adsorbent for selective separation/isolation of cytochrome c. AB - Fluoridized iron phosphate (F-FePO) is prepared via a hydrothermal protocol and characterized by means of (57)Fe Mossbauer spectra, Fourier transform infrared, and surface charge analysis. For the first time, F-FePO is used as an adsorbent for the adsorption of proteins, which exhibits favorable selectivity toward cytochrome c (cyt-c) in the presence of acidic and neutral proteins under controlled experimental conditions. At pH 10.5, an adsorption efficiency of 100% is achieved for 60 mg L(-1) cyt-c in 1.0 mL of sample solution using 6.0 mg F FePO. The adsorption behavior is consistent with the Langmuir adsorption model, corresponding to a theoretical adsorption capacity of 37.59 MUg mg(-1). The retained cyt-c on F-FePO could be readily collected by 0.1 mol L(-1) Na(2)CO(3) NaHCO(3) buffer (pH 10.5), deriving a recovery of 100%. Circular dichroism spectra indicate no conformational change for cyt-c after the adsorption and desorption processes, demonstrating the favorable biocompatibility of the fluoridized iron phosphate. F-FePO is employed for the selective isolation of cyt c from a spiked human whole blood, achieving satisfactory results by assay with SDS-polyacrylamide gel electrophoresis and native polyacrylamide gel electrophoresis. PMID- 21983983 TI - Elemental fingerprint profile of beer samples constructed using 14 elements determined by inductively coupled plasma-mass spectrometry (ICP-MS): multivariation analysis and potential application to forensic sample comparison. AB - Determination of elemental fingerprint profile of 40 commercial beer samples was performed using inductively coupled plasma-mass spectrometry combined with principal component analysis and receiver operating characteristic (ROC) analysis. Fourteen trace elements, (51)V, (52)Cr, (59)Co, (60)Ni, (75)As, (82)Se, (95)Mo, (111)Cd, (115)In, (121)Sb, (133)Cs, (208)Pb, (209)Bi, and (238)U, were monitored. All 40 beer samples are distinguishable by using the proposed method. ROC analysis showed that individual beer samples can be correctly identified via the magnitude of its correlation coefficient with respect to the other beers with low false positive rate. The obtained results suggested that the elemental fingerprint technique is feasible for sample differentiation and comparison. PMID- 21983984 TI - Ductular reactions in human liver: diversity at the interface. AB - Interest in hepatic ductular reactions (DRs) has risen in recent years because of a greater appreciation of their potential roles in regeneration, fibrogenesis, and carcinogenesis. However, confusion exists because there is significant, but often unappreciated diversity at the tissue, cellular, and subcellular levels in DRs of different diseases and stages of disease. DRs are encountered in virtually all liver disorders in which there is organ-wide liver damage and cell loss, but are also present in focal lesions such as focal nodular hyperplasia and adenoma. Moreover, diverse DR phenotypes can be present within any single disease entity, and are shaped by the etiology and evolution of the disease. Although much remains to be clarified, recent studies suggest that the diversity of appearances of the DRs are likely to reflect the differing signals at the anatomic, cellular, and molecular levels driving the proliferative response. These appear to determine the relative proportions of transit-amplifying cells, the degree of hepatocytic or cholangiocytic differentiation, and their relationships with stromal, vascular, and inflammatory components. The molecular signaling pathways governing these regenerative fate decisions closely replicate those found in human and other vertebrate embryos and more generally in stem cell niches throughout the body. Like the latter, complex interactions with matrix as well as mesenchymal and inflammatory cells, vessels, and innervation are likely to be of fundamental importance. Embracing systems/tissue biological approaches to exploring DRs, in addition to more traditional cellular and molecular biological techniques, will further enhance our understanding and, thereby, we believe potentiate new therapeutic possibilities. PMID- 21983985 TI - Dialysate bath and QTc interval in patients on chronic maintenance hemodialysis: pilot study of single dialysis effects. AB - INTRODUCTION: Serum concentrations of potassium (K) and calcium (Ca) influence ionic currents and play an important role in the duration of ventricular action potential. Further, the influence of alkalosis in reducing ionized calcium has been well known for a long time. The aim of this study was to assess the effects of different dialysate electrolytes and bicarbonate concentrations on changes of QTc interval in patients on chronic hemodialysis. METHODS: The study hemodialysis sessions were performed in 22 patients, with different electrolyte and bicarbonate concentrations in dialysate. Tested dialysate concentrations were K of 2 and 3 mmol/L; Ca 1.25, 1.5 and 1.75 mmol/L; and bicarbonate 30 and 34 mmol/L. An electrocardiogram (ECG) was recorded 1 hour before, at the end and every hour for 4 hours after each study dialysis session. QTc interval was measured from the beginning of the QRS complex to the end of a T wave on a 12 lead ECG. Blood was collected and K, total Ca, ionic Ca and pH evaluated. RESULTS: At the end of the study hemodialysis session with dialysate containing low K (2 mmol/L), low Ca (1.25 mmol/L) and high bicarbonate concentration (34 mmol), mean QTc interval was significantly prolonged compared with that recorded with dialysate containing high K (3 mmol/L), high Ca (1.75 mmol/L) and bicarbonate (30 mmol) (40 +/- 10 milliseconds vs. 2 +/- 2 milliseconds; p<0.01). Dialysate with low concentration of low Ca, K and high concentration of bicarbonate was an independent predictor of QTc; the combination of low Ca and K and high bicarbonate strongly increased the risk of prolonged QTc interval. CONCLUSION: The present pilot study shows that changes in QTc interval during hemodialysis depend on both electrolyte and bicarbonate concentrations in dialysate. PMID- 21983986 TI - Abated microRNA-195 expression protected mesangial cells from apoptosis in early diabetic renal injury in mice. AB - BACKGROUND: MicroRNAs are a class of highly conserved, small, noncoding RNAs that tailor gene expression mainly at the posttranscriptional level. The aim of the present study was to investigate the renal expression profiles of microRNAs and their potential involvement in early diabetic nephropathy. METHODS: Diabetic models were induced with streptozotocin in DBA/2 mice. MicroRNAs were detected by microarray and subjected to bioinformatics analyses. Real-time PCR and Western blots were performed. The relationships between pathological changes and microRNA expression were evaluated by linear regression analysis. Apoptosis and proliferation of cultured mesangial cells treated with microRNA inhibitor were determined by flow cytometry and MTT assay, respectively. RESULTS: Nine microRNAs, including miR-1187, miR-320, miR-214, miR-34a, miR-762, miR-466f, miR 720, miR-744 and miR-1937b, were increased significantly. Another 9 microRNAs, including miR-1907, miR-195, miR-568, miR-26b, miR-703, miR-1196, miR-194, miR 805 and miR-192, were decreased remarkably in diabetic mice. The levels of microRNA repressing BCL2 decreased. Accordingly, BCL2 levels were found elevated and caspase-3 and caspase-8 levels decreased in the diabetic group. MicroRNA-195 expression was negatively related to glomeruli diameter, mesangial score and extracellular matrix (ECM) accumulation. Moreover, the microRNA-195 inhibitor protected mesangial cells from apoptosis and promoted the cellular proliferation in vitro. CONCLUSIONS: These results demonstrated that the abated microRNA-195 expression protected mesangial cells from apoptosis, suggesting that the antiapoptosis in a microRNA-regulated manner may play an important role in the early stages of diabetic nephropathy. PMID- 21983987 TI - National primary care guidelines for England: impact on chronic kidney disease prevention in South Asian populations. AB - INTRODUCTION: This study evaluated the impact of national policy for kidney disease in primary care comparing South Asian (SA) and white European (WE) population groups. METHODS: Retrospective audits of primary care records of SA and WE adults diagnosed with diabetes in 2004 and 2007 were carried out in a total sample of 707 patients across 18 general practices within Luton, Leicester and West London. RESULTS: Four hundred patients (SA: n=241, and WE: n=159) were diagnosed as diabetic in 2004, and 307 (SA: n=178, and WE: n=129) in 2007. South Asian patients were 9-10 years younger, had lower systolic blood pressure than white Europeans at diagnosis in both years (136.1 vs. 141.4 mm Hg, p=0.01, in 2004; and 134 vs. 142.3 mm Hg, p=0.000, in 2007) and significantly higher HbA1c (8.6%, 63 mmol/L vs. 7.9%, 71 mmol/L) at diagnosis in 2004 than in 2007 (8.3%, 67 mmol/L vs. 8.2%, 66 mmol/L). Recording of the majority of variables associated with diabetic kidney disease increased across both patient groups between 2004 and 2007: albumin to creatinine ratio (up 13.0% in SA to 37.9%, and 15.1% in WE to 40.3%), estimated glomerular filtration rate (up 61.7% in SA to 70.8% and 75.6% in WE to 80.6%) and proteinuria (up 19.3% in SA to 46.3% and 26.1% in WE to 51.9%). CONCLUSIONS: Recording of indicators for diabetic kidney disease at diagnosis increased in both South Asians and white Europeans following introduction of national guidance to improve early detection and quality of care in the diabetic kidney disease care pathway. PMID- 21983988 TI - Uremic pruritus. AB - Uremic pruritus remains one of the most frustrating and potentially disabling symptoms in patients with end-stage renal disease. It affects up to 90% of patients on dialysis. Several hypotheses have been postulated for the possible underlying etiology, but none is conclusive. Aside from kidney transplantation, which is the only definitive treatment, therapeutic approaches have largely been empirical, and no firm evidence-based treatments are available. The main goal of therapy remains to minimize the severity of pruritus and improve the quality of life especially among those who are not transplantation candidates or are waiting for surgery. PMID- 21983989 TI - Adherence to treatment and hospitalization risk in hemodialysis patients. AB - BACKGROUND: The aim of this study was to evaluate whether adherence to treatment is associated with hospitalization risk in hemodialysis patients. METHODS: We completed a cohort analysis of risk factors during 1 census month (November) and 1 year of follow-up during 5 consecutive years (2002-2006) in all end-stage renal disease patients hemodialyzed in the Kaunas region. During the census month, we collected data on noncompliance defined as (i) skipping of a hemodialysis (HD) session, (ii) shortening of 1 or more HD sessions, (iii) presence of hyperkalemia, (iv) presence of hyperphosphatemia, or (v) interdialytic weight gain (IDWG). In addition, data on age, sex, disability status, comorbidities, anemia control, malnutrition and inflammation, calcium-phosphorus metabolism and hospitalization rate were collected. Relative risk of hospitalization was estimated using Cox regression evaluating time to first hospitalization. RESULTS: We analyzed 559 patients for a total of 1,163 patient-years during the 5 years of the study. On multivariate analysis, adjusting for ischemic heart disease, diabetes mellitus, higher number of comorbid conditions, higher systolic blood pressure before dialysis, worse disability status, lower hemoglobin, albumin and urea before dialysis, the relative risk for hospitalization increased by 1.1 for every additional percentage point of IDWG and by 1.19 with each 1 mmol/L rise of serum phosphorus level. Skipping or shortening of hemodialysis sessions and serum potassium level were not associated with hospitalization. CONCLUSIONS: Higher IDWG and higher serum levels of phosphorus independently increased the relative risk of hospitalizations in hemodialysis patients. With skipped and shortened dialysis sessions, higher serum potassium level was not associated with hospitalization risk. PMID- 21983990 TI - GABRG2 gene polymorphisms in Egyptian children with simple febrile seizures. AB - Mutations in the gamma-aminobutyric acid type A receptor (GABRG2) gene have been associated with generalized epilepsy, childhood absence epilepsy and febrile seizures. In the present study the authors investigated the association of polymorphism of the GABRG2 with simple febrile seizures (FS) in Egyptian children. Polymorphism at GABRG2 (SNP211037, Asn196Asn), on chromosome 5q33 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 100 Egyptian children with simple FS, and 120 healthy controls. The frequency of CC genotype of GABRG2 gene was significantly higher in children with simple FS compared to healthy children (p <= 0.0001). The C allele of GABRG2 was associated with increased risk for developing simple FS (OR: 2.15. 95% CI, 1.4-3.2. p <= 0.0001). The present findings suggested that the GABRG2 (SNP211037)-C allele could be a suitable genetic marker for prediction of susceptibility to simple FS in Egyptian children. PMID- 21983991 TI - Home made pneumatic otoscopy. PMID- 21983992 TI - [Venous thrombembolism in tumour patients]. AB - Venous thrombembolism (VTE) is one of the most frequent complication in cancer patients. The current options in prophylaxis and therapy have to be balanced against the risks of major bleeding and the burden for the patients. The Gesellschaft fur Thrombose- und Hamostaseforschung, the Deutsche Gesellschaft fur Palliativmedizin and the German speaking Societies of Hematology and Oncology have recently published guidelines on VTE in cancer patients. Recommendations include diagnostics, individual prophylaxis and treatment. PMID- 21983993 TI - The ProteoRed MIAPE web toolkit: a user-friendly framework to connect and share proteomics standards. AB - The development of the HUPO-PSI's (Proteomics Standards Initiative) standard data formats and MIAPE (Minimum Information About a Proteomics Experiment) guidelines should improve proteomics data sharing within the scientific community. Proteomics journals have encouraged the use of these standards and guidelines to improve the quality of experimental reporting and ease the evaluation and publication of manuscripts. However, there is an evident lack of bioinformatics tools specifically designed to create and edit standard file formats and reports, or embed them within proteomics workflows. In this article, we describe a new web based software suite (The ProteoRed MIAPE web toolkit) that performs several complementary roles related to proteomic data standards. First, it can verify that the reports fulfill the minimum information requirements of the corresponding MIAPE modules, highlighting inconsistencies or missing information. Second, the toolkit can convert several XML-based data standards directly into human readable MIAPE reports stored within the ProteoRed MIAPE repository. Finally, it can also perform the reverse operation, allowing users to export from MIAPE reports into XML files for computational processing, data sharing, or public database submission. The toolkit is thus the first application capable of automatically linking the PSI's MIAPE modules with the corresponding XML data exchange standards, enabling bidirectional conversions. This toolkit is freely available at http://www.proteored.org/MIAPE/. PMID- 21983994 TI - Surgical management of gastric perforation in the setting of gastric cancer. AB - BACKGROUND: Gastric perforation is a rare presentation of gastric cancer and is thought to be a predictor of advanced disease and, thus, poor prognosis. Guidelines do not exist for the optimal management strategy. We aimed to identify, review, and summarize the literature pertaining to perforation in the setting of gastric cancer. METHODS: A qualitative, systematic review of the literature was performed from January 1, 1985, to January 1, 2010. Searches of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were performed using search terms related to gastric cancer surgery. Abstracts were examined by two independent reviewers and a standardized data collection tool was used to extract relevant data points. Summary tables were created. RESULTS: Nine articles were included. Perforation was reported to occur in fewer than 5% of gastric cancer patients. Preoperative diagnosis of a gastric cancer was rated and occurred in 14-57% of patients in the papers reviewed. Mortality rates for emergency gastrectomy ranged from 0 to 50% and for simple closure procedures the rates ranged from 8 to 100%. Patients able to receive an R0 gastrectomy demonstrated better long-term survival (median 75 months, 50% 5-year) compared with patients who had simple closure procedures. CONCLUSIONS: Gastric cancer patients presenting with a gastric perforation demonstrate improved overall survival with an R0 resection; however, implementation of this management technique is complicated by infrequent preoperative gastric cancer diagnosis, and inability to perform an oncologic resection due to patient instability and intra abdominal contamination. PMID- 21983996 TI - Spatial pattern analysis of cruise ship-humpback whale interactions in and near Glacier Bay National Park, Alaska. AB - Understanding interactions between large ships and large whales is important to estimate risks posed to whales by ships. The coastal waters of Alaska are a summer feeding area for humpback whales (Megaptera novaeangliae) as well as a prominent destination for large cruise ships. Lethal collisions between cruise ships and humpback whales have occurred throughout Alaska, including in Glacier Bay National Park (GBNP). Although the National Park Service (NPS) establishes quotas and operating requirements for cruise ships within GBNP in part to minimize ship-whale collisions, no study has quantified ship-whale interactions in the park or in state waters where ship traffic is unregulated. In 2008 and 2009, an observer was placed on ships during 49 different cruises that included entry into GBNP to record distance and bearing of whales that surfaced within 1 km of the ship's bow. A relative coordinate system was developed in ArcGIS to model the frequency of whale surface events using kernel density. A total of 514 whale surface events were recorded. Although ship-whale interactions were common within GBNP, whales frequently surfaced in front of the bow in waters immediately adjacent to the park (west Icy Strait) where cruise ship traffic is not regulated by the NPS. When ships transited at speeds >13 knots, whales frequently surfaced closer to the ship's midline and ship's bow in contrast to speeds slower than 13 knots. Our findings confirm that ship speed is an effective mitigation measure for protecting whales and should be applied to other areas where ship-whale interactions are common. PMID- 21983995 TI - Infiltration of silica inside fibrillar collagen. PMID- 21983997 TI - Estimated soil respiration rates decreased with long-term soil microclimate changes in successional forests in southern China. AB - The response of soil respiration to short-term environmental factors changes has been well studied, whereas the influences of long-term soil microclimate changes on soil respiration are still highly unclear, especially in tropical ecosystems. We hypothesized that soil carbon accumulation in southern China, especially in mature forest during recent years, partly resulted from reducing soil respiration rates. To test this hypothesis, we analyzed the temporal trends and variations of air temperature, soil temperature and soil water content (hereafter referred to as SWC), and then estimated soil respiration rates in the 1980s and 2000s with soil temperature and SWC by regression model in three subtropical forests which are at early-, mid-, and advanced-successional stages, respectively, in Dinghushan Nature Reserve (hereafter referred to as DNR) in southern China. The annual mean ambient air temperature increased by 1.03 +/- 0.15 degrees C in the last 50 years (1954-2007) in DNR. Rainfall amount in the corresponding period did not change significantly, but rainfall pattern changed remarkably in the last three decades (1978-2007). Soil temperature is correlated with ambient air temperature. The average SWC was 36.8 +/- 8.4%, 34.7 +/- 8.1% and 29.6 +/- 8.1% in the 1980s, and then dropped sharply to 23.6 +/- 2.9%, 20.5 +/- 4.2% and 17.6 +/- 3.9% in the 2000s, for the advanced, mid- and early-successional forests, respectively. Concurrent changes of soil temperature and SWC may have a negative effect on soil respiration rates for all three forests, implicated that soil respiration may have a negative feedback to regional climate change and carbon could be sequestered in subtropical forests in southern China. PMID- 21983998 TI - Agave salmiana plant communities in central Mexico as affected by commercial use. AB - Agave salmiana is a native plant species harvested for the commercial production of mezcal (Agave spirits) in the highlands of central Mexico. The objective of this study was to identify vegetation changes in natural communities where A. salmiana has been differentially harvested for commercial purposes. Three plant community categories were identified in the state of Zacatecas based on their history of A. salmiana utilization: short (less than 10 years of use), moderate (about 25 years), and long (60 or more years). Species cover, composition, and density were evaluated in field surveys by use category. A gradient of vegetation structure of the communities parallels the duration of A. salmiana use. A. salmiana density was greatest (3,125 plants ha(-1)) in the short-use areas and less (892 plants ha(-1)) in the moderate-use areas, associated with markedly greater density of shrubs (200%) and Opuntia spp. (50%) in moderate-use areas. The main shrubs were Larrea tridentata, Mimosa biuncifera, Jatropha dioica and Buddleia scordioides while the main Opuntia species were Opuntia leucotricha and Opuntia robusta. A. salmiana density was least (652 plants ha(-1)) in the long use areas where shrubs were less abundant but Opuntia spp. density was 25% higher than in moderate-use areas. We suggest that shrubs may increase with moderate use creating an intermediate successional stage that facilitates the establishment of Opuntia spp. Long-term Agave use is generating new plant communities dominated by Opuntia spp. (nopaleras) as a replacement of the original communities dominated by A. salmiana (magueyeras). PMID- 21984000 TI - Editorial: emergence of polymer biotechnology. PMID- 21984003 TI - Meeting report: BioVision--a sumptuous table of food-for-thought. PMID- 21984005 TI - Effect of C3 transferase on human adipose-derived stem cells. AB - Human adipose-derived stem cells (ASCs) are adult pluripotent stem cells, which have the ability to differentiate into fat, cartilage, bone, or nerves that can be applied in tissue engineering. On the other hand, the exoenzyme C3 transferase (C3) is a Rho inhibitor. Once in the cytosol, the cell-penetrating moiety is released, thereby allowing C3 transferase to freely diffuse intracellularly and inactivate RhoA, RhoB, and RhoC, but not related GTPases such as Cdc42 or Rac1. In this study, we investigated ASC cytoskeletal changes induced by the addition of C3 employing immunofluorescence staining, changes in alpha-smooth muscle actin (a-SMA) gene expression employing real-time RT-PCR, and the Rho-inhibitory effect employing the pull-down assay. C3 significantly reduced stress fiber disruption and a-SMA expression 24 h after its addition at a concentration of 1 MUg/ml, and it also reduced the Rho activity level. While the correlation of the occurrence can be assumed, it requires further examination to verify it. C3 may be an effective inhibitor of intracellular signal transmission in ASC cytoskeletal control involving Rho. PMID- 21984006 TI - Insulin-induced hypoglycemia and stress oxidative state in healthy people. AB - The purpose of this study is to assess the immediate effects of insulin-induced hypoglycemia on the natural antioxidant superoxide dismutase activity, malondialdehyde concentration, total antioxidative capacity and total thiol group concentration in young healthy subjects. In this clinical trial, 16 healthy men with the mean age of 29.3 +/- 5.3 years (range 21-39 years) became volunteers to participate the study. Hypoglycemia was induced by intravenous administration of regular insulin 0.1 U/kg. Before and after inducing hypoglycemia, SOD activity was determined in red blood cells, whereas the MDA concentration was determined by thiobarbituric acid reactive substance method, total thiol groups by high performance liquid chromatography method and total antioxidant capacity by ferric reducing/antioxidant power. A significant increase was seen in the TBARS levels following insulin-induced hypoglycemia (0.19 +/- 0.07 vs. 0.38 +/- 0.16 nmol/g, P < 0.001), while a significant decrement occurred in the antioxidant power (FRAP value) (321.4 +/- 63.4 vs. 231.4 +/- 57.5, P < 0.001), total thiol concentration (2.3 +/- 0.8 vs. 1.3 +/- 0.5, P = 0.001) and SOD enzyme activity (29.4 +/- 8.2 vs. 23.1 +/- 6.1, P < 0.001) subsequent the hypoglycemia with insulin. PMID- 21984007 TI - Fabp4-Cre-mediated deletion of the miRNA-processing enzyme Dicer causes mouse embryonic lethality. PMID- 21984008 TI - Overexpression of a chloroplast-localized small heat shock protein OsHSP26 confers enhanced tolerance against oxidative and heat stresses in tall fescue. AB - Small heat shock proteins are involved in stress tolerance. We previously isolated and characterized a rice cDNA clone, Oshsp26, encoding a chloroplast localized small heat shock protein that is expressed following oxidative or heat stress. In this study, we transferred this gene to tall fescue plants by an Agrobacterium-mediated transformation system. The integration and expression of the transgene was confirmed by PCR, Southern, northern, and immunoblot analyzes. Compared to the control plants, the transgenic plants had significantly lower electrolyte leakage and accumulation of thiobarbituric acid-reactive substances when exposed to heat or methyl viologen. The photochemical efficiency of photosystem II (PSII) (Fv/Fm) in the transgenic tall fescue plants was higher than that in the control plants during heat stress (42 degrees C). These results suggest that the OsHSP26 protein plays an important role in the protection of PSII during heat and oxidative stress in vivo. PMID- 21984009 TI - Cervical disc arthroplasty versus fusion for single-level symptomatic cervical disc disease: a meta-analysis of randomized controlled trials. AB - OBJECTIVE: To evaluate the safety and effectiveness of cervical disc arthroplasty (CDA) versus anterior cervical discectomy and fusion (ACDF) for single-level symptomatic cervical disc disease. METHODS: We identified eligible randomized controlled trials (RCTs) in PubMed (April 2011), EMBASE (April 2011) and Cochrane Central Register of Controlled Trials (April 2011). Data were collected and extracted by two reviewers independently. The methodological quality and clinical relevance of the included studies were assessed. Data analysis was conducted with RevMan 5.0. RESULTS: Six RCTs involving 1,745 patients were included. The pooled analysis showed a higher prevalence of neurological and overall success [(P = 0.004, RR = 1.06, 95% CI = 1.02-1.10), (P = 0.0005, RR = 1.14, 95% CI = 1.06 1.22)], and a lower incidence of dysphagia and reoperation related to adjacent segment degeneration [(P = 0.04, RR = 0.30, 95% CI = 0.09-0.97), (P = 0.03, RR = 0.46, 95% CI = 0.23-0.91)] with CDA compared to ACDF. However, there was no statistical difference in neck disability index (P = 0.92, SMD = 0.01, 95% CI = 0.25 to 0.27), neck and arm pain scores[(P = 0.33, SMD = -0.12, 95% CI = -0.37 to 0.13), (P = 0.54, SMD = 0.17, 95% CI = -0.36 to 0.70)], incidence of complications related to the implant or surgical procedure and reoperation related to primary surgery [(P = 0.32, RR = 0.76, 95% CI = 0.45-1.30), (P = 0.09, RR = 0.48, 95% CI = 0.20-1.12)]. CONCLUSION: Compared with ACDF, CDA carry a lower incidence of dysphagia complications and reoperation related to adjacent segment degeneration, and a higher prevalence of neurological and overall success at 2 years postoperatively. As the poor quality of the included studies, it is still uncertain whether CDR is more effective and safer than ACDF treating single level symptomatic cervical disc disease. Future large-scale RCTs with long-term follow-up are needed to provide clear evidence. PMID- 21984010 TI - The immune response to group B streptococcus type III capsular polysaccharide is directed to the -Glc-GlcNAc-Gal- backbone epitope. AB - The structures of the branched capsular polysaccharides of group B streptococcus type III (GBSIIIPS) and Streptococcus pneumoniae type 14 (Pn14PS) are identical apart from the (alpha2->3)-linked sialic acid in the side chains of GBSIIIPS. The present study tries to determine the minimal epitope in GBSIIIPS, using both a panel of anti-Pn14PS mouse sera and sera of humans vaccinated with either Pn14PS or GBSIIIPS. Type-specific Pn14PS antibodies that recognize the branched structure of Pn14PS have a low affinity for the native GBSIIIPS. Desialylation of GBSIIIPS results in dramatically higher affinity of anti-Pn14PS antibodies. Epitope specific anti-Pn14PS mouse antibodies and human sera of PCV7 vaccinees only recognized structures with the branching element -Glc-(Gal-)GlcNAc-, in particular -Gal-Glc-(Gal-)GlcNAc- in Pn14PS. On the other hand anti-GBSIIIPS human antibodies recognize predominantly the linear structure in the backbone of Pn14PS or GBSIIIPS, i.e., -Glc-GlcNAc-Gal-. This difference in antigenicity of Pn14PS and GBSIIIPS is in agreement with the difference in flexibility of the two polysaccharides caused by the presence or absence of sialic acid. PMID- 21984011 TI - Surface-attached sensors for cation and anion recognition. AB - The development of surface-attached sensors for cationic and anionic guests is of intense current research interest. In addition to the environmental flexibility, robustness and reusability of such devices, surface-confined sensors typically exhibit an amplified response to target analytes owing to preorganization of the receptor. Whereas redox-active cations may be sensed by studying the cyclic voltammetry of host-guest systems containing ion-selective receptors attached to an appropriate electrode, redox-inactive ionic species require the use of electrochemical impedance spectroscopy, with appropriately functionalized electrodes and redox probes. Alternatively, receptors may be constructed that incorporate an electrochemical or optical reporter group within their structure to provide a macroscopic response to the presence of an ionic guest. This critical review seeks to present an up-to-date, although necessarily selective, account of the progress in the field, and provides insights into possible future developments, including the utilization of receptor-nanoparticle conjugates and mechanically interlocked receptors. PMID- 21984012 TI - Development and validation of an UPLC-MS/MS method for the determination of ionophoric and synthetic coccidiostats in vegetables. AB - In poultry farming, anticoccidial drugs are widely used as feed additives for the prevention and treatment of coccidiosis. Because coccidiostats and veterinary medicines, in general, are often poorly absorbed, manure from treated animals may contain high concentrations of these compounds. Experimental studies have shown that the uptake of veterinary medicines by plants from soil containing contaminated manure may occur. This leads to several questions regarding the impact on the environment, resistance problems, and public health and allergy issues. This work describes the development of a quantification method for coccidiostats in vegetables. Vegetables were spiked at 100 MUg kg(-1) (dry weight) with coccidiostats (monensin, narasin, lasalocid A, salinomycin, diclazuril, and nicarbazin) in order to optimize the extraction and clean-up. Possible critical factors (e.g., extraction solvent) were statistically examined by linear regression with the use of Plackett-Burman and full factorial designs. Final extracts were analyzed with ultra-performance liquid chromatography tandem mass spectrometry operating in multiple-reaction monitoring mode. Both the synthetic and ionophoric coccidiostats could be determined in a single run with an analysis time of 5 min. The developed method was validated taking into account the requirements of the Commission Decision 2002/657/EC as a guideline. The method is regarded as applicable for its intended purposes with quantification limits between 0.30 and 2.98 MUg kg(-1). This method could be used to establish possible maximum residue limits for coccidiostats in vegetables, as already exist for eggs, meat, and milk. PMID- 21984013 TI - The application of tandem aza-wittig reaction to synthesize artemisinin-guanidine hybrids and their anti-tumor activity. AB - Three series of novel artemisinin-guanidine hybrids 4a-4f, 8a-8h and 9a-9h have been facilely synthesized via four-component reaction (aza-Wittig reaction) and evaluated for their anti-tumor activities against A549, HT-29 and MDA-MB-231 cell lines in vitro. All of the tested compounds showed enhanced anti-tumor activities with IC(50) values ranging from 0.02 uM to 12.0 uM as compared to DHA (dihydroartemisinin). Among them, artemisinin derived dimers, compounds 9b (IC(50) = 0.05 uM), 9d (IC(50) = 0.06 uM) and 9f (IC(50) = 0.02 uM) were found to be most active against HT29 cells. PMID- 21984014 TI - Anti-tumor activity of new artemisinin-chalcone hybrids. AB - In an attempt to develop potent and selective anti-tumor agents, three new series of artemisinin-chalcone hybrids 10a-10g, 11a-11g and 12a-12h were designed, synthesized and screened for their anti-tumor activity against five cell lines (HT-29, A549, MDA-MB-231, HeLa and H460) in vitro. Among compounds 10a-g and 11a 11g, most of them displayed enhanced activity and good selectivity toward HT-29 and HeLa cell lines with IC(50) values ranging from 0.12 to 0.85 uM as compared with DHA (dihydroartemisinin). Compounds 10a and 11a are most active toward HeLa cells with IC(50) values of 0.12 and 0.19 uM. The results revealed that the presence of chalcone moiety is beneficial to their activity and selectivity. In addition, compounds 12a-12h containing a 'reversed chalcone' moiety showed only slight improvement in activity than those of DHA. PMID- 21984016 TI - Design, synthesis and antifungal activity of some new imidazole and triazole derivatives. AB - Triazole and imidazole are incorporated into the structures of many antifungal compounds. In this study a novel series of 1,2,4-triazole, imidazole, benzoimidazole, and benzotriazole derivatives was designed as inhibitors of cytochrome P450 14alpha-demethylase (14DM). These structures were docked into the active site of MT-CYP51, using Autodock program. Sixteen compounds with the best binding energy were synthesized. The chemical structures of the new compounds were confirmed by elemental and spectral ((1) H-NMR and Mass) analyses. All compounds were investigated for antifungal activity against Candida albicans, Candida tropicalis, Candida glabrata, Candida parapeilosis, Candida kruzei, Candida dubliniensis, Aspergillus fomigatus, Aspergillus flavus, Microsporum canis, Microsporum gypseum, Trichophyton mentagrophyte, Epidermophyton floccosum. Some compounds showed excellent in-vitro antifungal activity against most of the tested fungi. Compounds 2, 9, and 10 had antifungal activity against several resistant fungi against fluconazole and itraconazole. PMID- 21984015 TI - Synthesis of some novel D-glucuronic acid acetylated derivatives as potential anti-tumor agents. AB - A structurally diverse series of Delta(4,5) -uronamide derivatives have been chemically synthesized starting from D-glucuronic acid itself by means of acetylation, activation, amide bond formation and base-catalyzed elimination protocols. Structure elucidation for all products along with optimization of the synthetic steps is described. The synthesized compounds were evaluated for their in-vitro anti-tumor activity against MCF-7, TK-10 and UACC-62 cell lines. The compounds 5, 11, 13, 15 and 16 were the most active against TK-10 cell line. On the other hand, the most active compounds against the MCF-7 cell line were 11 and 15. However, compounds 5, 7, 11, 13, 15 and 16 were the most active against the UACC-62 cell line. PMID- 21984017 TI - Synthesis of novel thiazolyl-pyrimidines and their anticancer activity in vitro. AB - A series of novel compounds 7-43 were prepared via the condensation of enaminones 4a-h and the guanidines carbonate 6a-f. The structures of these newly synthesized compounds were confirmed by (1) H-NMR, MS, EA and IR. All the compounds were tested for their cytotoxic activity in vitro against human cancer cell lines including Ishikawa, A549, BEL-7404, SPC-A-01 and SGC-7901. Most of them showed moderate cytotoxic against the tested cell lines. Among them, the most potent compounds 9 and 30 exhibited more efficient activity against Ishikawa, A549. PMID- 21984018 TI - Synthesis, characterisation and biological evaluation of copper and silver complexes based on acetylsalicylic acid. AB - Metalcarbonyl complexes with ligands derived from acetylsalicylic acid demonstrated high cytotoxic potential against various tumor cell lines and strong inhibition of the cyclooxygenase enzymes COX-1 and 2. In this study we tried to achieve comparable effects with [alkyne]silver or copper trifluoromethanesulfonate complexes which are more hydrophilic then the uncharged metalcarbonyl derivatives. All compounds were evaluated for growth inhibition against breast (MCF-7, MDA-MB 231) and colon cancer (HT-29) cell lines and for COX-1 and COX-2 inhibitory effects at isolated isoenzymes. Pure ligands showed neither cytotoxic nor COX-inhibitory effects. While the silver complexes of (but 2-ynyl)-2-acetoxybenzoate (But-ASS-Ag) and (but-2-yne-1,4-diyl)-bis(2 acetoxybenzoate) (Di-ASS-But-Ag) were strong cytostatics, only the copper complex Di-ASS-But-Cu was active. At the COX enzymes the complexes were more effective than their ligands and aspirin. PMID- 21984019 TI - Silylation of N-heterocyclic carbene with aminochlorosilane and -disilane: dehydrohalogenation vs. Si-Si bond cleavage. AB - Reactions of the aminochlorosilane RSiHCl(2) and disilane R(2)Si(2)HCl(3) (R = (2,6-iPr(2)C(6)H(3))(SiMe(3))N) with an excess of 1,3-bis(tert-butyl)imidazol-2 ylidene resulted in the silylation of the NHC while reaction with the less hindered 1,3-diisopropyl-4,5-dimethyl-imidazol-2-ylidene yielded an NHC stabilized aminochlorosilylene. PMID- 21984020 TI - Lip nodules caused by hyaluronic acid filler injection: report of three cases. AB - Many dermal fillers have been used for reducing facial skin lines and for providing lip augmentation, and hyaluronic acid (HA) is one of the most widely used agents. One of the main commercial forms of HA is Restylane (Q Med, Sweden) produced by microbiological engineering techniques. Although HA is non immunogenic, hypersensitivity and Granulomatous foreign body reactions have been reported. Herein, we report three female patients (average age 56 years) who presented with firm nodular lesions of the lip and a history of injection with HA (Restylane, Q Med, Sweden). Histopathologically, all cases showed pools of amorphous hematoxyphilic material surrounded by bands of densely collagenized connective tissue with no inflammation or foreign body reaction. Histochemical stains confirmed the presence of acid mucopolysaccharides such as hyaluronic acid. We conclude HA (Restylane, Q Med, Sweden) is an inert filler that may persist at an injection site, resulting in a tumor-like nodule. PMID- 21984023 TI - Resonant inelastic X-ray scattering and X-ray absorption spectroscopy on the cathode materials LiMnPO4 and LiMn0.9Fe0.1PO4--a comparative study. AB - We present a study of the charge-state behavior of the Li-ion battery cathode materials Li(x)MnPO(4) and Li(x)Mn(0.9)Fe(0.1)PO(4) using X-ray absorption spectroscopy (XAS) and resonant inelastic X-ray scattering (RIXS). A set of six identical battery cathodes for each material have been cycled and left in different charge states in the range of x = 0.2...1.0 before disassembly in an Ar glove box. Unexpectedly, we find that the Mn 3d-bands are almost inert to the delithiation process, suggesting that Mn ions participate to a very small extent in the charge compensation process. In Li(x)Mn(0.9)Fe(0.1)PO(4) the Fe 3d-band shows much more response to delithiation than the Mn 3d-band. The O 2p-band hybridizes with the bands of the other ions in Li(x)MnPO(4) and Li(x)Mn(0.9)Fe(0.1)PO(4) and thus, indirectly, carries useful information about the effects of delithiation at all ion sites. We conclude that the redox reactions during lithiation/delithiation of these materials are complex and involve repopulation of charges for all constituent elements. PMID- 21984024 TI - Neighborhood-preserving visualization of adaptive structure-activity landscapes: application to drug discovery. PMID- 21984025 TI - Disruption of the gene encoding beta-1, 3-glucanase in marine-derived Williopsis saturnus WC91-2 enhances its killer toxin activity. AB - As the beta-1, 3-glucanase produced by the marine-derived Williopsis saturnus WC91-2 could inhibit the activity of the killer toxin produced by the same yeast, the WsEXG1 gene encoding exo-beta-1, 3-glucanase in W. saturnus WC91-2 was disrupted. The disruptant WC91-2-2 only produced a trace amount of beta-1, 3 glucanase but had much higher activity of killer toxin than W. saturnus WC91-2. After the disruption of the WsEXG1 gene, the expression of the gene was significantly decreased from 100% in the cells of W. saturnus WC91-2 to 27% in the cells of the disruptant WC91-2-2 while the expression of the killer toxin gene in W. saturnus WC91-2 and the disruptant WC91-2-2 was almost the same. During 2-l fermentation, the disruptant WC91-2-2 could produce the highest amount of killer toxin (the size of the inhibition zone was 22 +/- 0.7 mm) within 36 h when the cell growth reached the middle of the log phase. PMID- 21984026 TI - Amelioration of ischemia-reperfusion injury in an isolated rabbit lung model using OXANOH. AB - OBJECTIVE: Acute respiratory distress syndrome (ARDS) remains a major cause of morbidity and mortality. Oxygen-free radicals (OFRs) produced during ischemia and reperfusion (IR) have been implicated as the final common pathway in the pathogenesis of this syndrome. Spin traps have been shown to decrease IR injury in several animal lung models. The hydroxylamine, OXANOH (2-ethyl-2,5,5-trimethyl 3-oxazolidine) has been proposed as an ideal spin trap that would trap extra- and intracellular OFRs producing the stable radical, OXANO* (2-ethyl-2,5,5-trimethyl 3-oxazolidinoxyl). Electron microscopy was used to investigate whether OXANOH would protect against IR injury in the rabbit lung. METHODS: OXANOH was obtained by hydrogenation of its stable radical, OXANO* using a safe laboratory technique. Several doses of OXANOH were tested to identify a nontoxic dose. Two quantitative methods were used based on the average surface area of the alveoli and average number of alveoli per unit surface area using scanning electron microscopy (SEM). A total of 20 animals were subjected to 2 hours of ischemia followed by 4 hours of reperfusion. On reperfusion, the 4 groups (N = 5) received no treatment, OXANOH, superoxide dismutase (SOD)/catalase, or oxypurinol. RESULTS: A therapeutic dose of 250 MUmol/L of OXANO* was suggested in this in vitro model. All the 3 treatments showed significantly less injury compared to the control group and that SOD/catalase was significantly different from OXANOH and oxypurinol (P < .008). CONCLUSION: OXANOH ameliorated IR injury in the isolated rabbit lung, almost as effectively as SOD/catalase and oxypurinol. PMID- 21984027 TI - Limb outcome and mortality in lower and upper extremity arterial injury: a comparison using the National Trauma Data Bank. AB - OBJECTIVE: To examine the outcomes of lower extremity (LE) and upper extremity (UE) arterial trauma. METHODS: Retrospective review of 2008 version of National Trauma Databank. Adult patient with LE and UE arterial trauma was identified and outcomes were compared. RESULTS: There were 8311 cases of extremity arterial trauma and 37% involved the LE. The LE cohort had higher blunt injury (56.2% vs 37.4%; P < .0001). The LE cohort was more likely to require fasciotomy (23.6% vs 6.7%; P < .0001) and amputation (7.8% vs 1.3%; P < .0001). Complication (18.8% vs 5.1%; P < .0001) and mortality rate (7.7% vs 2.2%, P < .0001) were higher in the LE cohort. Regardless of extremity, blunt trauma was associated with higher mortality (4.8% vs 3.8%; P = .03) and amputation (6.7% vs 1.3%; P < .0001). In multivariable analysis, LE arterial trauma was associated with increased mortality (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.7-2.9; P < .0001) and amputation (OR 4.3, 95% CI 3.2-5.8; P < .0001). CONCLUSIONS: Lower and upper extremity arterial injuries have different modes of presentation and outcomes. Lower extremity arterial trauma is more commonly caused by blunt injury and associated with worse outcomes despite more intensive intervention. PMID- 21984029 TI - Recanalization of failed autogenous conduit utilizing laser revascularization. AB - The traditional approach for the treatment of restenosis of autogenous vein bypass has been revision of bypass with vein patch angioplasty, interposition jump graft, or thrombectomy procedures for those patients with extensive occlusive disease and limb-threatening ischemia. Endovascular intervention traditionally involves angioplasty of the graft; however, vessels with diffuse disease or extensive longitudinal lesions are generally difficult to revascularize utilizing this technique. Surgical revision of a threatened autogenous vein graft may carry a morbidity rate as high as 13.6%. We present a series of cases in which excimer laser atherectomy (LA) was used to recanalize an occluded autogenous saphenous vein bypass. Of the occluded vein bypasses failed angioplasty and were successfully atherectomized with LA measuring lengths of 35 and 30 cm, respectively. The infrainguinal has a 6-month follow-up, while the infragencular has a follow-up of 1 year, with resolution of presenting symptoms. PMID- 21984028 TI - Low-dose (1 microg/kg) clonidine premedication and hypotension after carotid artery surgery. AB - We investigated the role of low-dose clonidine intravenous (IV) premedication in arterial pressure variation during and after carotid endarterectomy (CEA). A total of 84 patients, American Society of Anesthesiologists (ASA) II-III, scheduled for elective CEA under general anesthesia participated in this study. The patients were divided into 2 groups: group P (n = 42) and group C (n = 42) and received N/S 0.9% (placebo) or clonidine 1 MUg/kg IV, respectively, 15 minutes before induction of anesthesia. Recovery times, number of patients needed to be treated for circulatory events (hypertension, hypotension, and bradycardia), number of circulatory events per patient, and consumption of vasoactive drugs (nitroglycerine, phenylphrine, and atropine) intraoperatively and the first 6 hours postoperatively were recorded. Significantly less hypertensive episodes were observed intraoperatively, but more hypotensive episodes were observed postoperatively in patients receiving clonidine. Intravenous premedication with low-dose clonidine (1 MUg/kg) seems to be effective in preventing hypertensive episodes during CEA under general anesthesia but seems to increase the incidence of hypotension postoperatively. PMID- 21984030 TI - Endovascular management of symptomatic cerebral malperfusion due to carotid dissection after type A aortic dissection repair. AB - PURPOSE: Type A acute aortic dissection is a surgical emergency, and supra-aortic trunk involvement may be complicated by stroke in 6% to 20% of cases. A 66-year old Caucasian female patient underwent a composite repair of the ascending aorta for type A aortic dissection. Postoperative period was complicated by episodes of "drop attack." Doppler ultrasound of supra-aortic trunks revealed an intimal flap occluding right internal carotid artery. TECHNIQUE: Multiple stenting was performed from carotid bifurcation to internal carotid artery in order to exclude the dissection intimal flap. After endovascular procedure physiatrist considered that motor functional improvement was better than expected, and we support that endovascular resolution of carotid malperfusion led to a better outcome. CONCLUSION: According to other experience, endovascular procedure resulted as a safe and effective way. Moreover, ultrasound monitoring of supra-aortic trunks in postoperative period is recommended. PMID- 21984031 TI - Superior mesenteric artery stent fracture leading to recurrent mesenteric ischemia. AB - We report 2 cases of patients with recurrent symptoms of mesenteric ischemic disease after percutaneous transluminal angioplasty (PTA) and stenting due to superior mesenteric artery stent fracture. Both patients were treated by redo PTA and stenting successfully. Stent fractures, their complications, and management are discussed. PMID- 21984034 TI - A miniaturized, optically accessible bioreactor for systematic 3D tissue engineering research. AB - Perfusion bioreactors are widely used in tissue engineering and pharmaceutical research to provide reliable models of tissue growth under controlled conditions. Destructive assays are not able to follow the evolution of the growing tissue on the same construct, so it is necessary to adopt non-destructive analysis. We have developed a miniaturized, optically accessible bioreactor for interstitial perfusion of 3D cell-seeded scaffolds. The scaffold adopted was optically transparent, with highly defined architecture. Computational fluid dynamics (CFD) analysis was useful to predict the flow behavior in the bioreactor scaffold chamber (that was laminar flow, Re = 0.179, with mean velocity equal to 100 microns/s). Moreover, experimental characterization of the bioreactor performance gave that the maximum allowable pressure was 0.06 MPa and allowable flow rate up to 25 ml/min. A method, to estimate quantitatively and non destructively the cell proliferation (from 15 to 43 thousand cells) and tissue growth (from 2% to 43%) during culture time, was introduced and validated. An end point viability test was performed to check the experimental set-up overall suitability for cell culture with successful results. Morphological analysis was performed at the end time point to show the complex tridimensional pattern of the biological tissue growth. Our system, characterized by controlled conditions in a wide range of allowable flow rate and pressure, permits to systematically study the influence of several parameters on engineered tissue growth, using viable staining and a standard fluorescence microscope. PMID- 21984033 TI - New prodrugs of the antiprotozoal drug pentamidine. AB - Pentamidine is an effective antimicrobial agent that is approved for the treatment of African trypanosomiasis but suffers from poor oral bioavailability and central nervous system (CNS) penetration. This work deals with the development and systematic characterisation of new prodrugs of pentamidine. For this reason, numerous prodrugs that use different prodrug principles were synthesised and examined in vitro and in vivo. Another objective of the study was the determination of permeability of the different pentamidine prodrugs. While some of the prodrug principles applied in this study are known, such as the conversion of the amidine functions into amidoximes or the O-alkylation of amidoximes with a carboxymethyl residue, others were developed more recently and are described here for the first time. These newly developed methods aim to increase the affinity of the prodrug for the transporters and mediate an active uptake via carrier systems by conjugation of amidoximes with compounds that improve the overall solubility of the prodrug. The different principles chosen resulted in several pentamidine prodrugs with various advantages. The objective of this investigation was the systematic characterisation and evaluation of eight pentamidine prodrugs in order to identify the most appropriate strategy to improve the properties of the parent drug. For this reason, all prodrugs were examined with respect to their solubility, stability, enzymatic activation, distribution, CNS delivery, and oral bioavailability. The results of this work have allowed reliable conclusions to be drawn regarding the best prodrug principle for the antiprotozoal drug pentamidine. PMID- 21984032 TI - Epigenetic modifications may play a role in the developmental consequences of early life events. AB - Many aspects of postnatal development are influenced by events before birth, including cognitive and language development. An adverse intrauterine environment, for example secondary to poor maternal nutritional status, multiple pregnancy, or late preterm birth, is associated with increased risks of delayed or impaired childhood development and altered physiology in adulthood that may predispose to increased risk of adult disease. Maternal periconceptional undernutrition and twin conception can both result in late preterm birth, but it is less clear whether cases of late preterm birth not following a recognized early pregnancy event may still have their origin in the periconceptional period. Thus, the very earliest periods of pregnancy, and perhaps even the pre-pregnancy period, may be an important period determining the developmental trajectory of the fetus, and thus both pregnancy and later health outcomes. Profound epigenetic modifications to the genome occur in the early embryo as a normal part of development. Recent evidence suggests that environmental signals acting during early development may also result in epigenetic changes which may play a role in mediating the association between early life exposures and later phenotype. PMID- 21984035 TI - Awareness of the Tuskegee syphilis study: impact on offenders' decisions to decline research participation. AB - Ethnic and racial minorities are often under-represented in research. There is considerable speculation that Blacks, in particular, are discouraged from research participation because of researcher improprieties in the U.S. Public Health Service (USPHS) Syphilis Study at Tuskegee (aka the Tuskegee Syphilis Study [TSS]), a 40-year (1932-1972) study in which investigators withheld medical treatment from African-American men infected with syphilis. We debriefed 281 offenders who declined participation in a research study to assess the extent to which knowledge of the TSS impacted their decisions not to enroll. Relatively few (44/281; 15.6%) reported awareness of the TSS. Half (n = 22) of these "aware" individuals could cite factually accurate information about the TSS, and only four individuals indicated that awareness of TSS had "somewhat" influenced their decision to not participate. Findings suggest that the legacy of the TSS played a relatively minor role in these offenders' decisions to decline research participation. PMID- 21984038 TI - Comparison of efficacy of letrozole and clomiphene citrate in ovulation induction in Indian women with polycystic ovarian syndrome. AB - OBJECTIVES: The objective of this study was to compare the efficacy of letrozole versus clomiphene citrate as an ovulation induction drug in polycystic ovarian syndrome (PCOS) patients of Indian origin. METHOD: One hundred and forty seven infertile PCOS patients were randomly given letrozole (2.5 mg) (n = 69) or clomiphene (100 mg) (n = 78) from day 3 to day 7 of menstrual cycle, followed-up with transvaginal serial folliculometry from day 9. 10,000 IU of human chorionic gonadotropin (hCG) was administered when at least 1 ovarian follicle was >= 18 mm in size. RESULTS: The pertinent results of the study are as follows: on the day of hCG injection, mean E2 level was significantly higher in the clomphene citrate group (817 +/- 286.70 pg/ml) in comparison with letrozole group (444.03 +/- 85.42 pg/ml). Mean endometrial development was 8.72 +/- 1.41 mm in the letrozole and 8.78 +/- 1.16 mm in the clomiphene group (P = 0.004). CONCLUSION: Letrozole has beneficial effect on endometrium, thereby potentially increasing pregnancy rates after successful ovulation induction in women with PCOS. PMID- 21984037 TI - Post-conditioning protecting rat cardiomyocytes from apoptosis via attenuating calcium-sensing receptor-induced endo(sarco)plasmic reticulum stress. AB - Our previous studies demonstrated that caclium-sensing receptor (CaR) stimulation elicited phospholipase C (PLC)-mediated inositol triphosphate (IP(3)) formation, leading to an elevation in [Ca(2+)](i) released from the endo(sarco)plasmic reticulum (ER) to induce ER stress and perturbations of ER function, which cause cardiomyocyte apoptosis during ischemia/reperfusion (I/R). The aim of this study was to determine whether the protection of post-conditioning (PC) from I/R heart injury involved relieving calcium-sensing receptor (CaR)-induced ER stress. Male Wistar rats were subjected to 30 min of ischemia followed by 2 h of reperfusion. The rats were post-conditioned after the 30 min of ischemia by three cycles of 10 s of reperfusion followed by 10 s of ischemia at the onset of reperfusion. Meanwhile, GdCl(3), an activator of CaR, and NPS-2390, a specific inhibitor, were administered. We found that the PC and PC with NPS-2390 groups improved the recovery of cardiac function during reperfusion compared to the IR and PC groups with GdCl(3), respectively. [Ca(2+)](i) and [Ca(2+)](ER) were determined using Fluo-4 AM and Fluo-5N AM, respectively, using laser confocal microscopy. [Ca(2+)](i) was significantly increased, whereas [Ca(2+)](ER) was significantly decreased in the I/R and PC groups with GdCl(3). The rate of apoptotic cells was significantly decreased as shown by TUNEL (Terminal deoxy-nucleotidyl transferase mediated dUTP nick end labeling) assay in PC and PC with NPS-2390 groups compared to the I/R and PC groups with GdCl(3). In the I/R and PC groups with GdCl(3), the activated fragments of caspase-12, the cleavage products of activating transcription factor 6 (ATF6) and phospho-JNK (c-Jun NH(2)-terminal kinase) were increased compared to the PC and PC with GdCl(3) groups. These results demonstrated that PC could protect the myocardium from I/R injury by inhibiting CaR-induced sarcoplasmic reticulum stress. PMID- 21984036 TI - Regulation of PMA-induced MUC5AC expression by heparin in human bronchial epithelial cells. AB - Mucus hypersecretion is a major pathophysiologic feature in chronic inflammatory airway diseases. Oxidative stress plays a pivotal role in this process. Recent studies have found that heparin has antioxidant effects which can reduce free radical damage. Here, we hypothesized that heparin has some influence on the expression of mucin 5AC (MUC5AC) induced by phorbol myristate acetate (PMA) in a bronchial epithelial cell line (HBE16), also we have investigated the potential mechanism involved in the process. We found that ROS, the mRNA of Duox1, EGFR and MUC5AC, as well as the protein levels of Duox1, p-EGFR, EGFR, and MUC5AC in the PMA group were significantly increased when compared with the control group (all P < 0.01). After pretreatment with heparin however, there was a significant decrease in ROS levels, the mRNA of Duox1, EGFR, and MUC5AC, and the protein levels of Duox1, p-EGFR, EGFR, and MUC5AC, when compared with the PMA group (all P < 0.01). MUC5AC protein in the supernatant was inhibited in a dose-dependent manner by heparin. Pretreatment with DMTU resulted in a significant decrease in ROS content, the mRNA of Duox1, EGFR, and MUC5AC as well as the protein levels of Duox1, p-EGFR, EGFR, and MUC5AC when compared with the PMA group (all P < 0.01). When cells were pretreated with both heparin and DMTU, there was a further reduction in ROS content, the mRNA of Duox1, EGFR, and MUC5AC as well as the protein levels of Duox1, p-EGFR, EGFR, and MUC5AC, when compared with either the PMA group, heparin group, or DMTU group (all P < 0.01). Our results show that PMA can induce MUC5AC expression by activation of the Duox1-ROS-TACE-TGF-alpha-EGFR signaling pathway. Heparin can decrease the level of Duox1, ROS production and block the PMA-induced activation of EGFR, thus inhibiting the overexpression of mucin MUC5AC in a dose-dependent manner. In addition to reducing ROS production, heparin may also inhibit the expression of MUC5AC through other signal mechanisms. PMID- 21984039 TI - Vaginal hysterectomy and multimodal anaesthesia with bipolar vessel sailing (Biclamp((r)) forceps) versus conventional suture technique: quality results' analysis. AB - PURPOSE: The medical and economic benefits of the transvaginal approach over the abdominal and laparoscopic methods are demonstrated in many studies. Vaginal hysterectomy with bipolar vessel sailing (BiClamp((r))) represents an example of mininvasive surgery and could be a valid and cost-benefit alternative in the surgical treatment of benign gynaecologic disease. BiClamp((r)) may be carried out according to Clave's technique with a good result in postoperative pain. METHODS: Prospective randomized study (Canadian Task Force classification I). We compared the vaginal hysterectomy with salpingo-oophorectomies with BiClamp((r)) and multimodal anaesthesia (group A 30 patients) with vaginal hysterectomy with salpingo-oophorectomies and spinal anaesthesia (group B 30 patients). RESULTS: The median operating time was 33.5 min for group A and 54.5 min for group B (p < 0.0001). The median blood loss was 59.25 ml in group A and 81.75 ml in group B. The median hospital stay was 1.6 +/- 0.58 days for group A and 2.55 +/- 0.66 days for group B. Postoperative pain was statistically different between groups in the immediate postoperatory times, at 2 and at 6 h from the surgery and at 10 p.m. (p < 0.0001). Analyses of cost-effectiveness have stated advantages in terms of costs and indirect-direct benefits but also in earlier resumption of working. CONCLUSIONS: BiClamp((r)) technique with multimodal anaesthesia has advantages from surgical, anaesthesiology and economic point of view. It is a minimally invasive surgery characterised by lower morbidity, quicker surgery times and reduced costs when compared to classical vaginal hysterectomy. BiClamp((r)) technique represents a new border in vaginal surgery. PMID- 21984041 TI - Functional and sensory properties of hen eggs with modified fatty acid compositions. AB - Foaming, emulsifying, gelling, and sensory properties of fresh and stored hen eggs fed with a diet supplemented with flax oil (FO), rapeseed oil (RO), fish oil (FISH), and by-product from black currant processing (BC) were investigated. With these diets, the omega6/omega3 fatty acid ratio of eggs varied from 1.5 to 5.8, while the ratio for eggs in the control group was 6.2. Compared to eggs in the control group, FO supplementation in the feed had statistically significant influences on the foaming properties of the fresh eggs. Eggs stored for 21 days lost part of their foaming properties in FISH oil supplemented group, but the foaming properties in all test groups were technically acceptable. The emulsifying properties of eggs in FO and FISH supplemented feeding groups were statistically different compared to control group. In boiled eggs, flax oil and fish oil supplementation induced off flavours in eggs, but no changes between the control group and test groups were found in the sensory properties of mayonnaise preparations. These results suggest that the egg processing industry may produce egg-based products using oil-supplemented eggs without major problems in functional or sensory properties. PMID- 21984040 TI - Combined intra-abdominal pelvic packing during cytoreductive surgery in advanced epithelial ovarian cancer: a case series. AB - INTRODUCTION: Uncontrollable hemorrhage during cytoreductive surgery for advanced carcinoma ovary is a major cause of peri-operative mortality. This case series presents a novel technique of "combined intra pelvic and intra-abdominal packing," a life saving approach for such situations. MATERIALS AND METHODS: This case series describes the retrospectively analyzed outcome of 16 non-consecutive patients with advanced epithelial ovarian cancer who underwent this 'packing' procedure in view of diffuse oozing and deteriorating patient condition. Three to six povidone-iodine soaked roller gauges were used and removal was done through exit sites on abdomen, 48 h after packing at bedside in 14 cases. 43 patients of carcinoma ovary who underwent debulking surgery during the same period but did not need packing were analyzed to compare underlying patient- and disease-related factors and complication rates. RESULTS: Operative mortality due to excessive primary hemorrhage was avoided in 14 out of 16 packed patients (87.5%). There was no notable increase in morbidity in cases compared with controls. CONCLUSION: Post-operative complication rates were more or less acceptable. This method can achieve acceptable survival rates in patients with advanced ovarian malignancy having severe primary hemorrhage. PMID- 21984042 TI - Mutuality, empowerment and the health-wealth model: the Scottish context. AB - This paper will offer an alternative paradigm to healthcare delivery by introducing the concept of mutuality and empowerment into the existing health wealth model. The backdrop is provided by Better Health, Better Care (Scottish Government 2007), Section 1 of which is entitled 'Towards a Mutual NHS'. In detail, the paper will: revisit what is meant by mutuality; advance the meaning of the 'public interest'; explore empowerment and community empowerment and its relationship to health; and introduce a model, which tries to link these concepts and terms together. It is hoped that this analysis will help researchers and practitioners alike further appreciate the important concept of mutuality and empowerment into the existing health-wealth model. PMID- 21984043 TI - The unconstrained local hardness: an intriguing quantity, beset by problems. AB - Developing a mathematical approach to the local hard/soft acid/base principle requires an unambiguous definition for the local hardness. One such quantity, which has aroused significant interest in recent years, is the unconstrained local hardness. Key identities are derived for the unconstrained local hardness, deltaMU/deltarho(r). Several identities are presented which allow one to determine the unconstrained local hardness either explicitly using the hardness kernel and the inverse-linear response function, or implicitly by solving a system of linear equations. One result of this analysis is that the problem of determining the unconstrained local hardness is infinitely ill-conditioned because arbitrarily small changes in electron density can cause enormous changes in the chemical potential. This is manifest in the exponential divergence of the unconstrained local hardness as one moves away from the system. This suggests that one should be very careful when using the unconstrained local hardness for chemical interpretation. PMID- 21984044 TI - Step-like enhancement of luminescence quantum yield of silicon nanocrystals. AB - Carrier multiplication by generation of two or more electron-hole pairs following the absorption of a single photon may lead to improved photovoltaic efficiencies and has been observed in nanocrystals made from a variety of semiconductors, including silicon. However, with few exceptions, these reports have been based on indirect ultrafast techniques. Here, we present evidence of carrier multiplication in closely spaced silicon nanocrystals contained in a silicon dioxide matrix by measuring enhanced photoluminescence quantum yield. As the photon energy increases, the quantum yield is expected to remain constant, or to decrease as a result of new trapping and recombination channels being activated. Instead, we observe a step-like increase in quantum yield for larger photon energies that is characteristic of carrier multiplication. Modelling suggests that carrier multiplication is occurring with high efficiency and close to the energy conservation limit. PMID- 21984046 TI - Prognostic framing of stakeholders' subjectivities: a case of all-terrain vehicle management on state public lands. AB - Management of all-terrain vehicle (ATV) use on Minnesota state forest lands has a contentious history and land managers are caught between ATV riders, non motorized recreationists, private landowners, and environmental advocates. In this paper, we demonstrate the usefulness of framing distinct perspectives about ATV management on Minnesota state public forests, understand the structure of these management perspectives, identify areas of consensus and disagreement, specify which stakeholders hold the various perspectives, clarify stakeholder perceptions of other stakeholders, and explore the implications for ATV planning and management. Using Q methodology, three distinct perspectives about how we should or should not manage ATVs resulted from our analysis, labeled Expert Management, Multiple Use, and Enforcement and Balance. A surprising degree of unanimity among the three management perspectives was found. Although some of the areas of agreement would be difficult to implement, others would be relatively simple to put into place. We suggest that land managers focus on widely accepted management actions to ameliorate commonly recognized problems, which may ease tensions between stakeholders and make tackling the tougher issues easier. PMID- 21984047 TI - A hierarchical approach to forest landscape pattern characterization. AB - Landscape spatial patterns have increasingly been considered to be essential for environmental planning and resources management. In this study, we proposed a hierarchical approach for landscape classification and evaluation by characterizing landscape spatial patterns across different hierarchical levels. The case study site is the Red Hills region of northern Florida and southwestern Georgia, well known for its biodiversity, historic resources, and scenic beauty. We used one Landsat Enhanced Thematic Mapper image to extract land-use/-cover information. Then, we employed principal-component analysis to help identify key class-level landscape metrics for forests at different hierarchical levels, namely, open pine, upland pine, and forest as a whole. We found that the key class-level landscape metrics varied across different hierarchical levels. Compared with forest as a whole, open pine forest is much more fragmented. The landscape metric, such as CONTIG_MN, which measures whether pine patches are contiguous or not, is more important to characterize the spatial pattern of pine forest than to forest as a whole. This suggests that different metric sets should be used to characterize landscape patterns at different hierarchical levels. We further used these key metrics, along with the total class area, to classify and evaluate subwatersheds through cluster analysis. This study demonstrates a promising approach that can be used to integrate spatial patterns and processes for hierarchical forest landscape planning and management. PMID- 21984045 TI - On the nature of C-H...F-C interactions in hindered CF3-C(sp3) bond rotations. PMID- 21984048 TI - The glucose dysmetabolism in the acute phase of non-diabetic ST-elevation myocardial infarction: from insulin resistance to hyperglycemia. AB - In the setting of acute myocardial infarction, hyperglycemia and acute insulin resistance may represent a stress response to myocardial injury mainly related to acute catecholamine release. By measuring glucose values and insulin resistance (Homeostatic Model Assessment index-HOMA), we evaluated in 356 non-diabetic patients with ST-elevation myocardial infarction (STEMI) undergone mechanical revascularization: (a) the acute glycometabolic response by evaluating insulin resistance, glucose levels, and their combination and (b) whether insulin resistance and increased glucose values (and their combination) are able to affect in-Intensive Cardiac Care Unit (ICCU) mortality and complications. In the overall population, 226 (63.5%) patients showed glucose values <=140 mg/dl (group B), while 130 patients had glucose values >140 mg/dl (group A) (36.5%). Within group B, insulin resistance (as inferred by positive HOMA index) was present in 125 patients (55.3%), whereas 101 patients (44.7%) exhibited normal values of HOMA index. Within group A, 109 patients (83.8%) were insulin resistant, while 21 patients (16.2%) had normal values of HOMA index. At multivariable analysis, glucose values were independently associated with in-ICCU mortality (OR: 7.387; 95% CI 2.701-20.201; P < 0.001) and complications (OR: 1.786; 95% CI 1.089-2.928; P = 0.022). In the early phase of STEMI, the acute glycometabolic response to stress is heterogeneous (ranging from no insulin resistance to glucose levels >140 mg/dl and, finally, to the combination of increased glucose values and insulin resistance). Increased glucose values are stronger prognostic factors since they are independently associated with in-ICCU mortality and complications. PMID- 21984049 TI - Neonatal jaundice is associated with a small increase in the risk of childhood type 1 diabetes: a meta-analysis of observational studies. AB - Published data on the role of neonatal jaundice as a risk factor for childhood type 1 diabetes mellitus is inconsistent. We aimed to review systematically, the evidence for an increased risk of type 1 diabetes in children diagnosed with neonatal jaundice. A comprehensive search of the published literature was performed to identify studies that had recorded the occurrence of neonatal jaundice in a group of children with type 1 diabetes and in a group of control children. Odds ratios (ORs) were extracted from reports or derived from tabulated data and then combined using a random effects meta-analysis. Data were available from 12 case-control studies and one retrospective cohort study. Overall, there was only weak evidence of an increase in the risk of type 1 diabetes in children who had neonatal jaundice (OR 1.14, 95% CI 0.99-1.32; P = 0.07), and there was some evidence of heterogeneity (I(2) = 53%, P = 0.01) mainly attributable to one study. An analysis restricted to studies not relying on parental recall showed a stronger, significant relationship (OR = 1.25, 95% CI 1.03-1.51; P = 0.02), although heterogeneity remained. This analysis found evidence of a small but statistically significant increase in childhood type 1 diabetes risk associated with neonatal jaundice but only for studies which used data from obstetric records. Jaundice caused by blood group incompatibility or requiring phototherapy may be associated with a greater increase in type 1 diabetes risk and deserves further study. PMID- 21984050 TI - How I do it: the stapled ileal J pouch at restorative proctocolectomy. AB - BACKGROUND: Ileal pouch-anal anastomosis (IPAA) following proctocolectomy is the preferred option for patients with medically refractory ulcerative colitis, indeterminate colitis, and familial adenomatous polyposis. However, it remains a procedure associated with morbidity and mortality. Pelvic sepsis, pouch fistulae, and anastomotic dehiscence predispose to pouch failure. We report our experience with an adaptation for the formation of the stapled ileal J pouch using the GIATM 100 stapling device (Covidien, Mansfield, Massachusetts, USA). When creating the J pouch, we remove the bevelled plastic protector from the thin fork of the stapling device, allowing the staple line to be completed to the tip of the stapled efferent limb of the pouch, thereby minimizing potential blind ending in the efferent limb and injury to the transverse staple line. METHODS: Patients undergoing elective IPAA at our institution over a 5-year period using this adapted stapling technique for creation of the ileal J pouch were reviewed. Data were collected from a prospectively maintained inflammatory bowel disease database, theater records, and patient chart review. RESULTS: Forty-one patients underwent IPAA using this technique at our institution during the study period. Postoperative morbidity was encountered in 11 of 41 patients including pelvic sepsis, pouch fistulae, anastomotic stricture, or leak. There was no morbidity observed related to a blind efferent limb or transverse staple line disruption. No mortality was observed in this series. CONCLUSION: Maximizing the length of the efferent fork of the GIA stapling device can reduce the length of redundant efferent J limb of the ileal J pouch. This may reduce the incidence of torsion, volvulus, distension, fistulae/sinuses, and pelvic sepsis/anastomotic leak following IPAA. PMID- 21984051 TI - Metal endoclips for the closure of the appendiceal stump in laparoscopic appendectomy. AB - Closure of the appendiceal stump in laparoscopic appendectomy is the most crucial part of the procedure. In this retrospective clinical study, we describe a technique for laparoscopic appendectomy, in which the appendiceal stump is secured by metal endoclips. Medical data of the patients who underwent laparoscopic appendectomy for acute appendicitis between January 2005 and January 2011 at our institution were reviewed. The patients who had their appendiceal stump secured by metal endoclips were recruited for the study. The outcome measures were the rate of intraoperative and postoperative complications, operative time, and the length of hospital stay. A total of 233 patients were included to the study. The rate of intraoperative and postoperative complications, the mean operative time, and median length of hospital stay were 3 and 4%, 31.1 (15-75) min, and 18 (8-96) h, respectively. The closure of the appendiceal stump with metal endoclips in laparoscopic appendectomy is simple, quick, and safe with outcomes comparable to those of other methods. PMID- 21984052 TI - Biliopancreatic diversion with Roux-en-Y gastric bypass and long limbs: advances in surgical treatment for super-obesity. AB - BACKGROUND: Over the past 14 years, we have used different malabsorptive bariatric operations to treat super-obesity. We compared the efficacy and safety of our preferred procedure for the last 8 years with previous methods used in super-obese. METHODS: Our first procedure was distal Roux-en-Y gastric bypass (distal RYGBP) (gastric pouch 15 +/- 5 mL, 80 cm biliopancreatic limb, 100 cm common limb [CL]). The second was distal RYGBP with short alimentary limb (distal RYGBP-sAL) (gastric pouch 15 +/- 10 mL, alimentary limb [AL] 250 cm, CL 100 cm). Our preferred procedure for the past 8 years has been biliopancreatic diversion with RYGB and long limbs (BPD-RYGB-LL) (gastric pouch 40 +/- 10 mL, AL 400 cm, CL 100 cm). RESULTS: Seventy-five patients underwent distal RYGBP, 44 distal RYGBP sAL, and 841 BPD-RYGB-LL. Eight years postoperatively, the mean BMIs were 39.0, 29.4, and 29.2, respectively. The greatest reduction of 47.6% was achieved with BPD-RYGB-LL (distal RYGBP 30.6%; distal RYGBP-sAL 43.1%). Mean excess weight loss was 51.3% for distal RYGBP, 76.5% for distal RYGBP-sAL, and 80.9% for BPD-RYGB LL. Six patients died at the early postoperative period. Sixteen patients died during the first eight postoperative years, of whom significantly more were after distal RYGBP-sAL (P = 0.0003). Complications were significantly more frequent after distal RYGBP-sAL (P = 0.001). All procedures led to rapid and sustained resolution of major comorbidities in almost all patients affected. Metabolic and nutritional deficiencies were similar and manageable. CONCLUSIONS: Our variant of biliopancreatic diversion (BPD-RYGB-LL) results in substantial and sustained weight loss in super-obese, without compromising safety. PMID- 21984053 TI - Dual roles of polyhydroxy matrices in the homocoupling of arylboronic acids catalyzed by gold nanoclusters under acidic conditions. PMID- 21984054 TI - Bimanual coordination affects motor task switching. AB - Task-switching paradigms have generally been used to investigate cognitive processes involved in decision making or allocating attention. This work extended the task-switching paradigm into the motor domain in order to investigate the consequences of an unexpected environmental perturbation on reaction time and movement time. Typically, task-switching paradigms have investigated consequences of rearranging task sets from one trial to the next; this work explored rearranging planned movements within the context of a single trial. Of particular interest was how the motor system reorganizes coordination patterns when reaching amplitude congruency is manipulated between the two hands. Results for Experiment 1 and the far distance in Experiment 2 indicated that reaction time switch costs were the smallest during congruent task-switch trials, where reaching amplitudes between the two hands were the same. This implies that a planned movement parameter for one hand is accessible for the other hand in the circumstance of an unexpected task switch. However, the reversed congruency effects found for the near distance in Experiment 2 suggest that the ability to capitalize on stored parameter information to decrease reaction time is dependent on environmental factors and task instructions. Movement time results showed that even if a movement with one hand is aborted in mid-execution, it can still influence the performance of the other hand during a task switch. This suggests that bimanual coordination can affect prehensile performance even though only one hand has a goal to achieve. PMID- 21984055 TI - Effects of enzyme replacement therapy on five patients with advanced late-onset glycogen storage disease type II: a 2-year follow-up study. AB - We examined the efficacy of 2-year enzyme replacement therapy (ERT) using recombinant human alpha-glucosidase (GAA; Myozyme(r)) in five long-term ventilator-dependent adults and aged patients with advanced, late-onset glycogen storage disease type II (GSDII, also known as Pompe disease). Although all patients had advanced respiratory failure and were ventilator-dependent for more than 6 years, four showed obvious improvements in muscle strength, pulmonary function, and activities of daily living after ERT. Improvement in each parameter was more prominent in the first year than in the second year. Values in the second year were still significantly better than those at study entry and indicate stabilization in the clinical status of all patients. These results suggest that ERT continues to be effective in the second year of treatment even in patients suffering from advanced late-onset GSDII disease with severe respiratory failure. PMID- 21984057 TI - Raman spectroscopy probing of self-assembled monolayers inside the pores of gold nanotube membranes. AB - Electroless deposition was used to coat porous alumina membranes with gold. This process reduced the pore diameters and provided a platform suitable for surface modifications with self assembled monolayers (SAMs). The surface enhanced Raman scattering (SERS) effect was employed in order to confirm and characterise the formation of SAMs of 3-mercaptobenzoic acid (mMBA) inside the pores of gold nanotube membranes prepared using porous alumina (PA) templates. The investigation of the coverage and reproducibility of SAMs within porous matrices is of utmost importance in the design of filtration membranes and sensing platforms. Raman spectroscopy is capable of spatially resolved techniques such as mapping which was used to characterise the distribution of mMBA assembly within the pores. Due to the highly ordered structure of porous alumina and well controlled electroless gold deposition, these gold coated membranes have the potential to develop into SERS active substrates for ultrasensitive sensing technologies. PMID- 21984056 TI - Depression and frailty in later life: a synthetic review. AB - BACKGROUND: Many of the symptoms, consequences, and risk factors for frailty are shared with late-life depression. However, thus far, few studies have addressed the conceptual and empirical interrelationships between these conditions. This review synthesizes existing studies that examined depression and frailty among older adults and provides suggestions for future research. METHODS: A search was conducted using PubMed for publications through 2010. Reviewers assessed the eligibility of each report and abstracted information on study design, sample characteristics, and key findings, including how depression and frailty were conceptualized and treated in the analysis. RESULTS: Of 133 abstracted articles, 39 full-text publications met inclusion criteria. Overall, both cross-sectional (n = 16) and cohort studies (n = 23) indicate that frailty, its components, and functional impairment are risk factors for depression. Although cross-sectional studies indicate a positive association between depression and frailty, findings from cohort studies are less consistent. The majority of studies included only women and non-Hispanic Whites. None used diagnostic measures of depression or considered antidepressant use in the design or analysis of the studies. CONCLUSIONS: A number of empirical studies support for a bidirectional association between depression and frailty in later life. Extant studies have not adequately examined this relationship among men or racial/ethnic minorities, nor has the potential role of antidepressant medications been explored. An interdisciplinary approach to the study of geriatric syndromes such as late-life depression and frailty may promote cross-fertilization of ideas leading to novel conceptualization of intervention strategies to promote health and functioning in later life. PMID- 21984058 TI - Traditional endonasal and microscopic sinus surgery complications versus endoscopic sinus surgery complications: a meta-analysis. AB - The aim of this study was to compare the incidence of complications of endoscopic sinus surgery (ESS) to the incidence of complications of traditional and microscopic sinus surgery. A meta-analysis was carried out on 28 series of patients (a total of 13,405) who had undergone ESS, 8 series of patients (3,887 in total) who had undergone traditional endonasal sinus surgery and 7 series of patients (1,630 in total) who had undergone microscopic sinus surgery. The authors used the Bayesian inference package WinBUGS operating from within the statistical computer program R (version 2.7.1). Major complications had a higher incidence after traditional sinus surgery than ESS but this fact did not cause a significant statistical difference, whereas microscopic surgery had significantly more complications than ESS (p < 0.05). Carrying out our meta-analytic study, comparing major and minor complications of endonasal surgical approaches, was very difficult due to several methodological biases of data extraction and evaluation from studies concerning a broad timespan. Regarding major complications, we only found a significant statistical difference (p < 0.05) between the endoscopic (1%) and the microscopic methods (2.0%), but, if we had analyzed the data considering the natural learning curve of the latest ESS surgical approach, and if we had not considered the results produced in the first 10 years (1988-1998) concerning ESS in our meta-analysis, we would have found a statistically significant difference (p < 0.05) between the endoscopic (0.4%) and the traditional (1.1%) approach as well. PMID- 21984059 TI - Diagnostic sensitivity of 18fluorodeoxyglucose positron emission tomography for detecting synchronous multiple primary cancers in head and neck cancer patients. AB - We assessed the sensitivity of positron emission tomography (PET) for detecting synchronous multiple primary cancers, particularly synchronous esophageal cancers in head and neck cancer patients. We retrospectively reviewed 230 head and neck cancer patients. All the patients routinely underwent the following examinations: urinalysis, occult blood, tumor marker detection [squamous cell carcinoma (SCC), cytokeratin fragment (CYFRA), and carcinoembryonic antigen (CEA)], esophagogastroduodenoscopy, colonoscopy (when CEA was high or occult blood was positive), abdominal ultrasonography, plain chest computed tomography (CT), and PET. Bronchoscopy was performed when CT revealed lung shadow of central region. Synchronous multiple primary cancers were detected in 42 (18.2%) patients. The diagnostic sensitivity of PET for synchronous primary cancers was as follows: esophagus, 7.6% (1/13); stomach, 25.0% (2/8); lung, 66.7% (4/6); head and neck, 75.0% (3/4); colon, 0% (0/1); kidney, 0% (0/1); and subcutaneous, 100% (1/1). The sensitivity of PET for detecting synchronous esophageal cancers is low because these are early-stage cancers (almost stage 0-I). Therefore, it is necessary to perform esophagogastroduodenoscopy for detecting synchronous esophageal cancers. PET is an important additional tool for detecting synchronous multiple primary cancers because the diagnostic sensitivity of PET in synchronous head and neck cancer and lung cancer is high. But PET has the limitation of sensitivity for synchronous multiple primary cancers because the diagnostic sensitivity of PET in synchronous esophageal cancer is very low. PMID- 21984060 TI - Congenital aural atresia surgery: transmastoid approach, complications and outcomes. AB - Repair of complete congenital aural atresia (CAA) could be a challenging procedure due to complications reported with CAA surgery such as facial nerve palsy, canal stenosis, graft lateralization, sensorineural hearing loss or the difficulty involved in the surgical technique. From 2006 to 2009, we used a one stage-modified transmastoid approach for surgical repair of 33 ears with complete CAA via a non-randomized controlled clinical trial. Some modifications in the technique of mastoidectomy, ossiculoplasty, fascia and skin grafting and meatoplasty have been described. Patients were followed up for 12 months to assess audiometric results and post-operative complications. Changes in air-bone gap and need for revision surgery or hearing aids were assessed at follow-up. There were no cases of facial weakness, dead ear or bony canal stenosis. Hearing success in 2 months follow-up was achieved in 72.7% of all patients. Success rate increased to 92.3% in patients with Jahrsdoefer's scores of 8 and above. Overall success rate decreased to 63.6% at 12 months follow-up. There were no significant difference in Jahrsdoerfer score of patients with successful first surgical attempt and those who needed revision surgery (P value >0.056). Also patients of lower age (less than 5-years-old) did not have more need for revision surgery when compared with older patients (P value >0.36). However, being a syndromic patient did increase the need for revision surgery (P value <0.04). Age was not a predictor of meatal/canal stenosis and patients with lower Jahrsdoerfer scores could also achieve good results. PMID- 21984061 TI - Do GP referral guidelines really work? Audit of an electronic urgent referral system for suspected head and neck cancer. AB - We adapted the 2002 Scottish Referral Guidelines for suspected squamous cell carcinoma of the head and neck (SCCHN) as a set of "alarm symptoms." These were then incorporated into a new Suspected Cancer Urgent Referral Electronically (SeCURE) system enabling immediate electronic referral from primary care to the appropriate hospital-based multi-disciplinary cancer team. All referrals made via the SeCURE system during the first year of its implementation were reviewed retrospectively. One hundred and ninety patients were urgently referred, of whom 15 (8%) were ultimately diagnosed with SCCHN. This audit demonstrated overall poor compliance with the referral guidelines. Although the electronic referral system helped for speedy clinic appointments, there was a low pick up rate of positive head and neck cancer cases. Continuing education for GPs is important and following discussion with colleagues in primary care, steps have been taken to reinforce awareness and more appropriate use of the SeCURE system. PMID- 21984062 TI - Epistaxis: some aspects of laterality in 326 patients. AB - Lateralization of primary epistaxis was prospectively studied in 326 patients at Radebeul Elblandklinikum. The male-female-ratio was 1.3:1. A slight dominance of the right side (45% right vs. 39% left) was found in all patients. Further analyzed were the relationship to the localization of bleeding (anterior or posterior), the age and possible causes or risk factors. Nose bleeding from the posterior nasal portion appears to be statistically significantly higher than on both sides of anterior epistaxis. No statistically significant age dependence of laterality of epistaxis was observed in the age groups which we selected. However, nosebleed appears more frequently in women under the age of 50 years in both nostrils. With identified risk factors, idiopathic epistaxis occurs more frequently on the right side than does nosebleed. Mechanical trauma (intranasal sprays or nose picking) is a possible factor explaining the dominance of epistaxis on the right side, especially in idiopathic cases. PMID- 21984063 TI - HMGA1 expression in human gliomas and its correlation with tumor proliferation, invasion and angiogenesis. AB - High-mobility group A1 (HMGA1) protein is an architectural transcription factor widely expressed during embryonic development and tumor progression. The purpose of this research was to investigate the expression of HMGA1 in malignant gliomas with different WHO classification and to study the correlation of HMGA1 expression with tumor proliferation, invasion, and angiogenesis. Expression of HMGA1, Ki-67, MMP-9, VEGF-A, and MVD in malignant gliomas and their correlation were studied in 60 samples of different WHO classification by use of immunohistochemistry, and in 27 randomly selected samples by use of real-time quantitative PCR. Immunohistochemistry results showed that nuclear immunostaining of HMGA1 protein was not observed in normal brain tissues but was observed in 96.7% (58 of 60) of malignant gliomas including high (+++) in 15 (25.0%), moderate (++) in 28 (46.7%), and negligible to low (0-+) in 17 (28.3%) samples. Expression of HMGA1 protein was significantly higher in glioblastoma multiforme than in WHO grade II (P = 0.002) and WHO grade III gliomas (P = 0.024). HMGA1 protein expression correlated significantly with expression of Ki-67 (r = 0.530, P = 0.000), MMP-9 (r = 0.508, P = 0.000), VEGF-A (r = 0.316, P = 0.014), and MVD (r = 0.321, P = 0.012), but not with sex (r = 0.087, P = 0.510) and age (r = 0.121, P = 0.358). Real-time quantitative PCR results, also, were indicative of HMGA1 overexpression in glioblastoma multiforme compared with WHO grade II (P = 0.043) and WHO grade III (P = 0.031) gliomas. HMGA1 gene expression correlated significantly with gene expression of Ki-67 (r = 0.429, P = 0.025), MMP-9 (r = 0.443, P = 0.024), and VEGF-A (r = 0.409, P = 0.034). These results indicated that expression of HMGA1 correlates significantly with malignancy, proliferation, invasion, and angiogenesis of gliomas. We conclude that HMGA1 may be a potential biomarker and rational therapeutic target for human tumors. PMID- 21984065 TI - Droplet microfluidics--a tool for protein engineering and analysis. PMID- 21984064 TI - Phase I study of panobinostat in combination with bevacizumab for recurrent high grade glioma. AB - Bevacizumab is frequently used to treat patients with recurrent high-grade glioma (HGG), but responses are generally not durable. Panobinostat is a histone deacetylase inhibitor with anti-neoplastic and anti-angiogenic effects and may work synergistically with VEGF inhibitors. We performed a phase I study to evaluate the safety and tolerability of the combination of orally administered panobinostat with bevacizumab in patients with recurrent HGG. Patients with recurrent HGG were treated on a 3 + 3 trial design. Patients received bevacizumab 10 mg/kg every other week in combination with oral panobinostat. The starting dose of panobinostat was 20 mg three times per week, weekly (cohort 1). Due to concerns for thrombocytopenia with the weekly dosing regimen, the protocol was amended to examine an every other week regimen. Cohort 2 received panobinostat 20 mg three times per week, every other week, and cohort 3 received 30 mg three times per week, every other week. Dose-limiting toxicity during the first 30 days was used to determine the maximum-tolerated dose. Twelve patients (median age 50, median KPS 90) with recurrent HGG were enrolled. One dose-limiting toxicity (DLT) (Grade 3 thrombocytopenia) was observed in cohort 1. No DLTs were observed in cohorts 2 and 3. The following grade 3 toxicities were seen in one patient each: thrombocytopenia, hypophosphatemia, esophageal hemorrhage, and deep venous thrombosis. There were no grade 4 or 5 toxicities. There were three patients with partial responses and seven with stable disease. The recommended doses for further study are oral panobinostat 30 mg three times per week, every other week, in combination with bevacizumab 10 mg/kg every other week. A phase II clinical trial in recurrent HGG is underway. PMID- 21984066 TI - The role of curcumin on intestinal oxidative stress, cell proliferation and apoptosis after ischemia/reperfusion injury in rats. AB - The aim of this study was to demonstrate the role of curcumin on oxidative stress, cell proliferation and apoptosis in the rat intestinal mucosa after ischemia/reperfusion (I/R). A total of 30 male Wistar albino rats were divided into three groups: sham, I/R and I/R+ curcumin; each group contain 10 animals. Sham group animals underwent laparotomy without I/R injury. After I/R groups animals underwent laparotomy, 1 h of superior mesenteric artery ligation were followed by 1 h of reperfusion. In the curcumin group, 3 days before I/R, curcumin (100 mg/kg) was administered by gastric gavage. All animals were sacrificed at the end of reperfusion and intestinal tissues samples were obtained for biochemical and histopathological investigation in all groups. Curcumin treatment significantly decreased the elevated tissue malondialdehyde levels and increased of reduced superoxide dismutase, and glutathione peroxidase enzyme activities in intestinal tissues samples. I/R caused severe histopathological injury including mucosal erosions and villous congestion and hemorrhage. Curcumin treatment significantly attenuated the severity of intestinal I/R injury, with inhibiting of I/R-induced apoptosis and cell proliferation. These results suggest that curcumin treatment has a protective effect against intestinal damage induced by intestinal I/R. This protective effect is possibly due to its ability to inhibit I/R-induced oxidative stress, apoptosis and cell proliferation. PMID- 21984067 TI - A small Tim homohexamer in the relict mitochondrion of Cryptosporidium. AB - The apicomplexan parasite Cryptosporidium parvum possesses a mitosome, a relict mitochondrion with a greatly reduced metabolic capability. This mitosome houses a mitochondrial-type protein import apparatus, but elements of the protein import pathway have been reduced, and even lost, through evolution. The small Tim protein family is a case in point. The genomes of C. parvum and related species of Cryptosporidium each encode just one small Tim protein, CpTimS. This observation challenged the tenet that small Tim proteins are always found in pairs as alpha3beta3 hexamers. We show that the atypical CpTimS exists as a relatively unstable homohexamer, shedding light both on the early evolution of the small Tim protein family and on small Tim hexamer formation in contemporary eukaryotes. PMID- 21984068 TI - The architecture of long-range haplotypes shared within and across populations. AB - Homologous long segments along the genomes of close or remote relatives that are identical by descent (IBD) from a common ancestor provide clues for recent events in human genetics. We set out to extensively map such IBD segments in large cohorts and investigate their distribution within and across different populations. We report analysis of several data sets, demonstrating that IBD is more common than expected by naive models of population genetics. We show that the frequency of IBD pairs is population dependent and can be used to cluster individuals into populations, detect a homogeneous subpopulation within a larger cohort, and infer bottleneck events in such a subpopulation. Specifically, we show that Ashkenazi Jewish individuals are all connected through transitive remote family ties evident by sharing of 50 cM IBD to a publicly available data set of less than 400 individuals. We further expose regions where long-range haplotypes are shared significantly more often than elsewhere in the genome, observed across multiple populations, and enriched for common long structural variation. These are inconsistent with recent relatedness and suggest ancient common ancestry, with limited recombination between haplotypes. PMID- 21984071 TI - Time lag between Ambrosia sensitisation and Ambrosia allergy: a 20-year study (1989-2008) in Legnano, northern Italy. AB - OBJECTIVES: Ambrosia is spreading invasively in many European countries. Therefore, surveys showing the long-term consequences regarding the prevalence of sensitisation and allergy rates are needed. The aim of this study was to analyse the development of Ambrosia sensitisation and clinical symptoms over a period of 20 years among the patients of the allergy unit in Legnano in relation to the measured pollen concentrations. Legnano is situated near Milan in a region in northern Italy, known for its high Ambrosia pollen loads. METHODS: The sensitisation of patients to Ambrosia and other aeroallergens was tested by a skin prick test. The patients were interviewed about their clinical symptoms and the time of incidence of the symptoms. On average, 1100 patients per year were included in this study in the years 1989-2008. The daily pollen concentration was measured with volumetric Hirst type pollen traps. RESULTS: The sensitisation rate to Ambrosia increased from 24% to over 70% among the patients whose skin prick tests were positive to pollen. In 1989, about 45% of the Ambrosia sensitised patients suffered from respiratory symptoms (rhinitis and/or asthma) in late summer. After 5 years, this percentage increased to 70% and finally reached 90%. The prevalence of asthma was initially 30% among the Ambrosia sensitised patients and increased slightly to 40%. CONCLUSION: The extent of the consequences of high Ambrosia pollen concentrations is not ascertainable over the short term. Sensitisation rates have constantly increased over a period of more than 15 years, and moreover the incidence of allergy is delayed during the first years. PMID- 21984069 TI - Macrophage-mediated inflammation in metabolic disease. AB - Metabolism and immunity are two fundamental systems of metazoans. The presence of immune cells, such as macrophages, in metabolic tissues suggests dynamic, ongoing crosstalk between these two regulatory systems. Here, we discuss how changes in the recruitment and activation of macrophages contribute to metabolic homeostasis. In particular, we focus our discussion on the pathogenic and protective functions of classically and alternatively activated macrophages, respectively, in experimental models of obesity and metabolic disease. PMID- 21984072 TI - Neoangiogenesis of a serpentine middle cerebral artery aneurysm. PMID- 21984073 TI - A case of tremor reduction and almost complete ageusia under bilateral thalamic (VIM) deep brain stimulation in essential tremor--a therapeutic dilemma. AB - Essential tremor (ET) is a neurological disorder that can be treated effectively by means of bilateral thalamic ventral intermediate nucleus (VIM) deep brain stimulation (DBS). We present a rare case of stimulation-dependent reversible ageusia that poses a therapeutic dilemma on the one hand and serves as an instructive example to elucidate the as yet incompletely defined gustatory pathways on the other. A 69-year-old patient with successful reduction of his disabling upper extremity ET experienced an almost complete but during stimulation cessation reversible ageusia under bilateral VIM DBS. An evaluation of diffusion tensor (DTI) neuroimaging studies was performed in order to detect effective electrode positions and volumes of activated tissue (VTA) in relation to the medial lemniscus (ML) and dentato-rubro-thalamic tract (DRT). Repeated subjective gustometry was conducted with differential manipulation of stimulation settings. This case report stresses the importance of fiber tracts for DBS surgery. Reconciled with previous findings in lesion cases, we assume the coexistence of decussating and non-decussating fibers in the gustatory tract combined with hemispheric dominance in the processing of gustatory information. A therapeutic option for this dilemma may be a patient-selectable stimulation program or bipolar stimulation establishing a smaller ovoid VTA. PMID- 21984070 TI - Monocyte recruitment during infection and inflammation. AB - Monocytes originate from progenitors in the bone marrow and traffic via the bloodstream to peripheral tissues. During both homeostasis and inflammation, circulating monocytes leave the bloodstream and migrate into tissues where, following conditioning by local growth factors, pro-inflammatory cytokines and microbial products, they differentiate into macrophage or dendritic cell populations. Recruitment of monocytes is essential for effective control and clearance of viral, bacterial, fungal and protozoal infections, but recruited monocytes also contribute to the pathogenesis of inflammatory and degenerative diseases. The mechanisms that control monocyte trafficking under homeostatic, infectious and inflammatory conditions are being unravelled and are the focus of this Review. PMID- 21984074 TI - The connexin mimetic peptide Gap27 increases human dermal fibroblast migration in hyperglycemic and hyperinsulinemic conditions in vitro. AB - Significant increases in skin wound healing rates occur by reducing connexin mediated communication (CMC). Gap27, a connexin (Cx) mimetic peptide targeted to the second extracellular loop of Cx43, which inhibits CMC, increases migration of human keratinocytes and dermal fibroblasts. To examine the efficacy of Gap27 in a hyperglycemic and hyperinsulinemic in vitro environment, cell migration, gap junction, and Cx hemichannel functionality and cell-substrate adhesion assays were performed on human dermal fibroblasts and diabetic fibroblast and keratinocytes. To investigate fibroblast genes involved in these processes, extra cellular matrix (ECM) and adhesion gene expression was determined with a PCR array. Gap27 increased fibroblast migration in both euglycemia/euinsulinemia and hyperglycemia/hyperinsulinemia, and influenced migration in diabetic keratinocytes. Hyperglycemia/hyperinsulinemia reduced gap junction coupling in fibroblasts and Gap27 reduced CMC and cell adhesion to substrata in fibroblasts cultured in high glucose. Migrating dermal fibroblast ECM and cell adhesion genes were found to be differentially regulated by Gap27 in euglycemia and hyperglycemia. The PCR array showed that Gap27 upregulated 34 genes and downregulated 1 gene in euglycemic migrating fibroblasts. By contrast in hyperglycemia, Gap27 upregulated 1 gene and downregulated 9 genes. In euglycemic conditions, Gap27 induced upregulation of genes associated with ECM remodeling, whereas in hyperglycemia, ECM component genes were downregulated by Gap27. Thus, Gap27 improves cell migration during scrape-wound repair in hyperglycemia/hyperinsulinemia conditions in vitro, although migration of diabetic cells is less influenced. Our results suggest that this increase in motility may occur by decreasing gap junction and hemichannel activity and altering gene expression in the adhesion and ECM pathway. PMID- 21984075 TI - Effects of APRIL (TNFSF13) polymorphisms and splicing isoforms on the secretion of soluble APRIL. AB - Functional APRIL (TNFSF13) is a secreted trimer generated by furin protease cleavage. We previously reported the association of APRIL haplotypes formed by two nonsynonymous polymorphisms, Gly67Arg and Asn96Ser, with systemic lupus erythematosus. Here, we tested the hypothesis that polymorphisms and/or alternative splicing may influence the generation of soluble APRIL (sAPRIL). HEK 293T cells were transfected with plasmids containing one of the six combinations of splicing isoforms (alpha or beta) and haplotypes (susceptible, neutral, or protective). APRIL concentrations were quantitated in the cell lysates and supernatants using an enzyme-linked immunosorbent assay (ELISA). The association between splicing efficiency and polymorphisms was analyzed using quantitative reverse transcription polymerase chain reaction (RT-PCR). The efficiency of cleavage by furin protease was analyzed using western blotting. Although both splicing isoforms were cleaved by furin protease, sAPRIL was not detected in the supernatant of the cells transfected with the beta isoform, regardless of the haplotype. This suggested that, similarly to B-cell activating factor (BAFF), one of the major APRIL splicing isoforms may not be secreted as a functional molecule. Furthermore, the secretion of sAPRIL was decreased in the transfectants expressing the protective haplotype. An association between the polymorphisms and splicing efficiency or furin cleavage efficiency was not detected. In conclusion, these observations suggested that both alternative splicing and polymorphisms may affect the generation of functional sAPRIL. PMID- 21984076 TI - A triple spin-labeling strategy coupled with DEER analysis to detect DNA modifications and enzymatic repair. AB - In a spin: Spin-labeled oligonucleotides produced by click chemistry can be studied by EPR, by using a DEER sequence. This was used to test a complex triple labeling strategy with damaged DNA. Extensive and accurate analysis of DNA structure and enzymatic repair processes were performed after digestion by EndoIV. Modified DNA structures and DNA-protein interactions can now be readily studied. PMID- 21984111 TI - Bacterial predators possess unique membrane lipid structures. AB - Bdellovibrio-and-like organisms (BALO) are a phylogenetically diverse group of predatory prokaryotes that consists of the two families Bdellovibrionaceae and Bacteriovoracaceae. We investigated the phospholipid composition of the three important BALO strains Bacteriovorax stolpii (DSM 12778), Bdellovibrio bacteriovorus HD100 (DSM 50701) and Peredibacter starrii (DSM 17039). We confirmed the presence of sphingophosphonolipids in B. stolpii, while we characterized sphingophosphonolipids with a 2-amino-3-phosphonopropanate head group for the first time. In B. bacteriovorus HD100 phosphatidylthreonines were found and, thus, B. bacteriovorus is the second prokaryote investigated so far possessing this rare lipid class. In the third analyzed organism, P. starrii, we observed phosphatidylethanolamine structures with an additional N-glutamyl residue, which form the first reported class of amino acid-containing phosphatidylethanolamines. PMID- 21984112 TI - cis-9,trans-11,cis-15 and cis-9,trans-13,cis-15 CLNA mixture activates PPARalpha in HEK293 and reduces triacylglycerols in 3T3-L1 cells. AB - Scientific research is constantly working to find new molecules that are effective in preventing excessive accumulation of body fat. The aim of the present work was to assess the potential agonism on PPARalpha and PPARgamma of a conjugated linolenic acid (CLNA) isomer mixture, consisting of two CLNA isomers (cis-9,trans-11,cis-15 and cis-9,trans-13,cis-15). Secondly, we aimed to analyze the effects of this mixture on triacylglycerol accumulation in 3T3-L1 mature adipocytes. Luciferase transactivation assay was used to analyze whether the CLNA mixture activated PPARs. The expression of several enzymes and transcriptional factors involved in the main metabolic pathways that control triacylglycerol accumulation in adipocytes was assessed by real time RT-PCR in 3T3-L1 adipocytes treated for 20 h with the CLNA mixture. The mixture activated PPRE in cells with PPARalpha receptor over-expression, but not those with PPARgamma over-expression. Decreased triacylglycerol was found in treated adipocytes. The lowest dose (10 MUM) increased HSL expression and the highest dose (100 MUM) increased ATGL gene expression. The other genes analyzed remained unchanged. The hypothesis of an anti-obesity action of the analyzed CLNA mixture, based on increased lipid mobilization in adipose tissue, can be proposed. PMID- 21984113 TI - Relationships between airway hyperresponsiveness, inflammation, and calibre in asthma. AB - BACKGROUND: Previous studies have focused upon the relationship between airway inflammation and hyperresponsiveness with different conclusions. We re-examined the relationship between airway inflammation (FE(NO)), hyperresponsiveness to methacholine (AHR), and calibre (FEV(1) % predicted) in mild-to-moderate asthmatics. METHODS: We searched our database for asthmatics who had attended our research department. FEV(1) % predicted, FE(NO), and methacholine PC(20) were collected. Patients were divided into groups based upon AHR as follows: severe (<0.5 mg/ml, group A), moderate (>0.5-2 mg/ml, group B), and mild (>2-8 mg/ml, group C), and upon FE(NO): low (<25 ppb, group D), medium (25-50 ppb, group E), and high (>50 ppb, group F). RESULTS: In 208 asthmatics, when stratified by AHR, there was an 8.5% difference in FEV(1) % predicted (95% CI 2.6-14.4%; P = 0.002) and a 29% difference in FE(NO) between groups A and C (95% CI 2-48%; P = 0.034). When stratified by FE(NO,) there was a 1.29 doubling dilution difference in methacholine PC(20) (95% CI 0.26-2.33; P = 0.009) between groups D and F. There was no difference between FEV(1) % predicted when grouped by FE(NO). Multivariate regression analysis with covariates, including inhaled corticosteroids, supported our findings from categorical analysis. CONCLUSIONS: We found no relationship between airway inflammation and calibre, whilst showing significant relationships between AHR and airway calibre and AHR and airway inflammation. Whilst relationships exist, the lack of complete concordance highlights the important role each contributes to the assessment of the asthmatic individual. PMID- 21984114 TI - Multi-structural thermodynamics of C-H bond dissociation in hexane and isohexane yielding seven isomeric hexyl radicals. AB - The C-H bond dissociation processes of n-hexane and isohexane involve 23 and 13 conformational structures, respectively in the parent molecules and 14-45 conformational structures in each of the seven isomeric products that we studied. Here we use the recently developed multi-structural (MS) thermodynamics method and CCSD(T)-F12a/jul-cc-pVTZ//M06-2X/6-311+G(2df,2p) potential energy surfaces to calculate the enthalpy, entropy, and heat capacity of n-hexane, isohexane, and seven of the possible radical products of dissociation of C-H bonds. We compare our calculations with the limited experimental data and with values obtained by group additivity fits used to extend the experimental data. This work shows that using the MS method involving a full set of structural isomers with density functional geometries, scaled density functional frequencies, and coupled cluster single-point energies can predict thermodynamic functions of complex molecules and bond dissociation reactions with chemical accuracy. The method should be useful to obtain thermodynamic data for complex molecules for which such data has not been measured and to obtain thermodynamic data at temperatures outside the temperature range where measurements are available. PMID- 21984115 TI - Improved survival time trends for glioblastoma using the SEER 17 population-based registries. AB - The EORTC/NCIC 22981/26981 study demonstrated an improvement in median overall survival (OS) from 12.1 to 14.6 months in patients with glioblastoma (GBM) who received temozolomide with post-operative radiotherapy (RT). The current study was performed to determine if those results translated into a survival benefit in a population-based cohort. Patients diagnosed between 2000 and 2006 with a GBM who underwent surgery and post-operative RT were selected from the Surveillance, Epidemiology and End Results database. Patients were grouped into time periods: 2000-2001, 2002-2003, 2004 and 2005-2006 (which represented those treated after the EORTC/NCIC trial presentation in 2004). Relative survival (RS) was estimated by the Kaplan-Meier method, and Cox multivariable regression modeling was used to estimate proportional hazard ratios (HR). Over time, there was improvement in the median and 2-year RS of 12 months and 15% for 2000-2001, 13 months and 19% for 2002-2003, 14 months and 24% for 2004, and 15 months and 26% for 2005-2006 (P < 0.0001 compared to 2000-2001 and 2002-2003; P = 0.07 compared to 2004). The estimated adjusted HR showed that patients diagnosed in 2005-2006 had significantly improved survival when compared to patients diagnosed in 2000-2001 (HR = 0.648, 95% CI 0.604-0.696). The median and 2 year RS of 15 months and 26% in 2005-2006 was similar to the median and 2 year OS of 14.6 months and 26% seen in the EORTC/NCIC phase III study. These results are encouraging and suggest that the current treatment of glioblastoma nationwide is now associated with an improved survival compared to previous time cohorts. PMID- 21984116 TI - Feasibility of pharmacy-initiated pharmacogenetic screening for CYP2D6 and CYP2C19. AB - PURPOSE: Our purpose was to investigate the feasibility of pharmacy-initiated pharmacogenetic (PGt) screening in primary care with respect to patient willingness to participate, quality of DNA collection with saliva kits, genotyping, and dispensing data retrieved from the pharmacy. METHODS: Polypharmacy patients aged >60 years who used at least one drug with Anatomical Therapeutic Chemical (ATC) code N06AA01-N06AX19 (antidepressants), A02BC01 A02BC05 (proton-pump inhibitors), N05AA01-N05AH04 (antipsychotics), or C07AB02 (metoprolol) in the preceding 2 years were randomly selected. DNA was collected with saliva kits and genotyped for CYP2D6 and CYP2C19 with the AmpliChip. Pharmacy dispensing records were retrieved and screened for drugs interacting with the patient's CYP2D6 and CYP2C19 genotype by using the evidence-based PGt guidelines from the Dutch Pharmacogenetics Working Group. RESULTS: Out of the 93 invited patients, 54 (58.1%) provided informed consent. Nine saliva samples (16.7%) contained too little DNA. Call rates for CYP2D6 and CYP2C19 were 93.3% and 100%, respectively. Frequencies of genotype-predicted phenotype were 2.4%, 38.1%, 54.8%, and 4.8% for CYP2D6 poor metabolizers (PM), intermediate metabolizers (IM), extensive metabolizers (EM), and ultrarapid metabolizers (UM) respectively. For CYP2C19 genotype-predicted phenotype, frequencies were 2.2%, 15.6%, and 82.2% for PM, IM, and EM, respectively. CONCLUSIONS: This study shows that pharmacy-initiated PGt screening is feasible for a primary care setting. PMID- 21984117 TI - iLoc-Plant: a multi-label classifier for predicting the subcellular localization of plant proteins with both single and multiple sites. AB - Predicting protein subcellular localization is a challenging problem, particularly when query proteins may simultaneously exist at, or move between, two or more different subcellular location sites. Most of the existing methods can only be used to deal with the single-location proteins. Actually, multiple location proteins should not be ignored because they usually bear some special functions worthy of our notice. By introducing the "multi-labeled learning" approach, a new predictor, called iLoc-Plant, has been developed that can be used to deal with the systems containing both single- and multiple-location plant proteins. As a demonstration, the jackknife cross-validation was performed with iLoc-Plant on a benchmark dataset of plant proteins classified into the following 12 location sites: (1) cell membrane, (2) cell wall, (3) chloroplast, (4) cytoplasm, (5) endoplasmic reticulum, (6) extracellular, (7) Golgi apparatus, (8) mitochondrion, (9) nucleus, (10) peroxisome, (11) plastid, and (12) vacuole, where some proteins belong to two or three locations but none has >= 25% pairwise sequence identity to any other in a same subset. The overall success rate thus obtained by iLoc-Plant was 71%, which is remarkably higher than those achieved by any existing predictors that also have the capacity to deal with such a stringent and complicated plant protein system. As a user-friendly web-server, iLoc-Plant is freely accessible to the public at the web-site or . Moreover, for the convenience of the vast majority of experimental scientists, a step-by-step guide is provided on how to use the web-server to get the desired results without the need to follow the complicated mathematic equations presented in this paper for its integrity. It is anticipated that iLoc-Plant may become a useful bioinformatics tool for Molecular Cell Biology, Proteomics, Systems Biology, and Drug Development. PMID- 21984118 TI - Sleep: narcolepsy associated with the 2009 H1N1 pandemic in China. PMID- 21984119 TI - Has the European union achieved a single pharmaceutical market? AB - This paper explores price differences in the European Union (EU) pharmaceutical market, the EU's fifth largest industry. With the aim of enhancing quality of life along with industry competitiveness and R&D capability, many EU directives have been adopted to achieve a single EU-wide pharmaceutical market. Using annual 1994-2003 data on prices of molecules that treat cardiovascular disease, we examine whether drug price dispersion has indeed decreased across five EU countries. Hedonic regressions show that over time, cross-country price differences between Germany and three of the four other EU sample countries, France, Italy and Spain, have declined, with relative prices in all three as well as the fourth country, UK, rising during the period. We interpret this as evidence that the EU has come closer to achieving a single pharmaceutical market in response to increasing European Commission coordination efforts. PMID- 21984120 TI - One-dimensional polyelectrolyte/polymeric semiconductor core/shell structure: sulfonated poly(arylene ether ketone)/polyaniline nanofibers for organic field effect transistors. PMID- 21984121 TI - Risk stratification for 1-year mortality in acute heart failure: classification and regression tree analysis. AB - BACKGROUND: Simple tools for risk stratification of patients with acute heart failure (AHF) are an unmet clinical need, particularly regarding long-term mortality. METHODS: We prospectively enrolled 610 consecutive patients presenting to the emergency department with AHF. The diagnosis of AHF was adjudicated by two independent cardiologists. The classification and regression tree (CART) analysis was used to develop a simple risk algorithm. This was internally validated by cross-validation. RESULTS: One-year follow-up was complete in all patients (100%). A total of 201 patients (33%) died within 360 days. The CART analysis identified blood urea nitrogen (BUN) and age as the best single predictors of 1 year mortality and patients were categorised to three risk groups: high risk group (BUN >27.5 mg/dl and age >86 years), intermediate risk group (BUN >27.5 mg/dl and age <= 86 years) and low risk group (BUN <= 27.5 mg/dl). The Kaplan Meier curves showed a significant increase in mortality in the high risk group compared with the lower risk groups (log-rank test p <0.001). The hazard ratio regarding 1-year mortality between patients identified as low and high risk was 2.0 (95% confidence interval, 1.7-2.4), with statistically significant differences between all risk groups (p <0.001). The likelihood-based 95% confidence set for the age- and the urea-threshold is contained in the rectangular set defined by 25 mg/dl <= urea threshold <=30.6 mg/dl and 76 years <= age threshold <=96 years. CONCLUSION: These results suggest that AHF patients at low, intermediate and high risk for death within 360 days can be easily identified using patient's demographics and laboratory data obtained at presentation. Application of this simple risk stratification algorithm may help to improve the management of these patients. PMID- 21984122 TI - Plasma nucleic acid analysis by massively parallel sequencing: pathological insights and diagnostic implications. AB - Over the past 15 years there has been increasing interest in the biology and diagnostic applications of circulating DNA in the plasma of human subjects. In particular, DNA from a fetus, a tumour, a transplanted organ and injured tissues has been found in the plasma of pregnant women, cancer patients, transplant recipients and patients suffering from multiple pathologies, respectively. The advent of massively parallel sequencing has given us a quantitative and powerful tool for studying circulating DNA on a genome-wide level. Using this approach, fetal chromosomal aneuploidies can be robustly detected using maternal plasma. Furthermore, a genome-wide genetic map of a fetus can also be constructed using this approach. This method has also allowed one to identify tumour-associated chromosomal translocations, which can then be detected in plasma. The direct application of massively parallel sequencing to the serum of cancer patients has also allowed quantitative aberrations that are associated with malignancy to be detected in serum. The use of massively parallel sequencing on the plasma of transplantation recipients has opened up an approach for detecting rejection. The application of circulating DNA sequencing has also opened up a new method for elucidating the quantitative aberration of circulating DNA in many pathological conditions. Such developments would provide new modalities for molecular diagnostics and would improve our understanding of the biology of circulating nucleic acids. PMID- 21984123 TI - Notch signalling is off and is uncoupled from HES1 expression in Ewing's sarcoma. AB - Notch can act as an oncogene or as a tumour suppressor and thus can either promote or inhibit tumour cell growth. To establish Notch status in Ewing's sarcoma family of tumours (ESFT), we investigated the Notch pathway by gene expression profiling meta-analysis or immunohistochemistry in samples obtained from 96 and 24 ESFT patients, respectively. We found that although Notch receptors were highly expressed, Notch did not appear to be active, as evidenced by the absence of Notch receptors in cell nuclei. In contrast, we show that Notch receptors known to be active in colon adenocarcinoma, hepatocarcinoma, and pancreatic carcinoma stain cell nuclei in these tumours. High expression of the Notch effector HES1 transcription factor, usually used as a surrogate marker for active Notch, was also restricted to outside of the nucleus in the majority of ESFT, and analysis of HES1 gene targets indicated HES1 to be transcriptionally inactive. Neither forced activation nor pharmacological or genetic blocking of Notch affected HES1 expression in ESFT cells, indicating HES1 expression to be uncoupled from the Notch pathway. Additional functional studies in ESFT cell lines confirmed Notch to be switched off. Finally, unlike experiments in which HES1 expression was modulated, experimental activation of Notch in ESFT cell lines via several means blocked cell proliferation and reduced their clonogenic potential in soft agar. These indicate that HES1 is uncoupled from Notch in ESFT, that EWS-FLI1-mediated inhibition of Notch contributes to ESFT aggressive cell growth, and support a role for Notch in ESFT tumour suppression, at least partly through the Notch effector HEY1. PMID- 21984124 TI - Low-dose paclitaxel ameliorates fibrosis in the remnant kidney model by down regulating miR-192. AB - Transforming growth factor (TGF)-beta has been shown to play a central role in the development of tubulointerstitial fibrosis, which can be corrected via treatment with paclitaxel. The biology of microRNA (miR) can be modulated by paclitaxel. We hypothesized that paclitaxel may attenuate renal fibrosis in a rat model of remnant kidney disease by inhibiting TGF-beta induced-miRs. Rats in groups of 12 were subjected to 5/6 nephrectomy and received low-dose intraperitoneal injection of paclitaxel. Renal functions were assessed at 8 weeks. The TGF-beta signalling cascade and ECM proteins were evaluated by real time polymerase chain reaction (TRT-PCR) and immunofluorescence microscopy. Animals with remnant kidneys developed hypertension, which was not relieved with paclitaxel treatment. However, paclitaxel treatment resulted in dampening the proteinuric response, reduction in serum BUN, creatinine levels and urine protein : creatinine ratio and normalization of creatinine clearance. These effects were accompanied by the inhibition of Smad2/3 activation, attenuation of renal fibrosis and normalization of integrin-linked kinase (ILK), COL(I)A1, COL(IV)A2 and alpha-SMA expression. Also, paclitaxel down-regulated the expression of miR 192, miR-217 and miR -377, while miR-15 was up-regulated in the remnant kidney. In vitro, in tubular epithelial cells (NRK-52E), paclitaxel also inhibited TGF beta1-induced Smad2/3 activation and normalized ILK, COL(I)A1, COL(IV)A2 and alpha-SMA expression. Furthermore, ChIP analyses indicated that Taxol suppressed Smad3-mediated miR-192 transcriptional activity. Over-expression of miR-192 in NRK-52E mimicked the changes seen in the remnant kidney, while inclusion of miR 192 inhibitor in the culture medium blocked TGF-beta1-induced COL(I)A1 and COL(IV)A2 expression, while ILK and alpha-SMA were unaffected. These data suggest that low-dose paclitaxel ameliorates renal fibrosis via modulating miR-192 pathobiology and TGF-beta/Smad signalling. PMID- 21984125 TI - Kaposi's sarcoma-associated herpesviral IL-6 and human IL-6 open reading frames contain miRNA binding sites and are subject to cellular miRNA regulation. AB - Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a viral interleukin 6 (vIL 6) that mimics many activities of human IL-6 (hIL-6). Both vIL-6 and hIL-6 play important roles in stimulating the proliferation of tumours caused by KSHV. Here, we provide evidence that a miRNA pathway is involved in regulation of vIL-6 and hIL-6 expression through binding sites in their open reading frames (ORFs). We show a direct repression of vIL-6 by hsa-miR-1293 and hIL-6 by hsa-miR-608. The repression of vIL-6 by miR-1293 was reversed by disruption of the vIL-6 miR-1293 seed match through the introduction of point mutations. In addition, expression of vIL-6 or hIL-6 in KSHV-infected cells could be enhanced by transfection of the respective miRNA inhibitors. In situ hybridization of human lymph node sections revealed that miR-1293 is primarily expressed in the germinal centre but is deficient in the mantle zone of lymph nodes, where the expression of vIL-6 is often found in patients with KSHV-associated multicentric Castleman's disease, providing evidence of an anatomical correlation. Taking these factors together, our study indicates that IL-6 expression can be regulated by miRNA interactions in its ORF and provides evidence for the role of these interactions in the pathogenesis of KSHV-associated diseases. PMID- 21984126 TI - Hypoxia-inhibited dual-specificity phosphatase-2 expression in endometriotic cells regulates cyclooxygenase-2 expression. AB - Endometriosis is one of the most common gynaecological diseases that significantly reduces the life qualify of affected women and their families. Aberrant expression of cyclooxygenase-2 (COX-2), and thus over-production of prostaglandin E(2) (PGE(2) ) has been shown to play critical roles in the development of this disease. However, the mechanism responsible for COX-2 over expression remains obscure. Here, we provide evidence for what we believe is a novel mechanism in regulating COX-2 expression in endometriotic stromal cells. Dual-specificity phosphatase-2 (DUSP2), a nuclear phosphatase that inactivates mitogen-activated protein kinase (MAPK), is markedly down-regulated in stromal cells of ectopic endometriotic tissues, which results in prolonged activation of extracellular signal-regulated kinase (ERK) and p38 MAPK and increased COX-2 expression. Expression of DUSP2 is inhibited by hypoxia inducible factor-1alpha (HIF-1alpha) at the transcriptional level. Treatment of normal endometrial stromal cells with hypoxia, or chemicals that cause HIF-1alpha accumulation, results in DUSP2 down-regulation, prolonged ERK phosphorylation and COX-2 over expression. In contrast, forced expression of DUSP2 under hypoxia abolishes HIF 1alpha-induced ERK phosphorylation and COX-2 expression. Furthermore, suppression of DUSP2 by HIF-1alpha in eutopic endometrial stromal cells increases sensitivity of cox-2 gene to interleukin-1beta stimulation, a phenomenon resembling endometriotic stromal cell characteristics. Taken together, these data suggest that DUSP2 is an important molecule in endometrial physiology and that hypoxia inhibited DUSP2 expression is a critical factor for the development of endometriosis. PMID- 21984127 TI - Overexpression of the Flii gene increases dermal-epidermal blistering in an autoimmune ColVII mouse model of epidermolysis bullosa acquisita. AB - Epidermolysis bullosa (EB) is a severe genetic skin fragility syndrome characterized by blister formation. The molecular basis of EB is still largely unknown and wound healing in patients suffering from EB remains a major challenge to their survival. Our previous studies have identified the actin remodelling protein Flightless I (Flii) as an important mediator of wound repair. Here we identify Flii as a novel target involved in skin blistering. Flii expression was significantly elevated in 30 patients with EB, most prominently in patients with recessive dystrophic EB (RDEB) who have defects in production of type VII collagen (ColVII). Using an autoimmune ColVII murine model of EB acquisita (EBA) and an immunocompetent-ColVII-hypomorphic genetic mouse model of RDEB together with murine Flii alleles, we investigated the contribution of Flii to EB. Overexpression of Flii produced severe blistering post-induction of EBA, while decreased Flii reduced blister severity, elevated integrin expression, and improved ColVII production. Flii(+/-) blistered skin showed reduced alpha-SMA, TGF-beta1, and Smad 2/3 expression, suggesting that decreasing Flii may affect fibrosis. In support of this, Flii-deficient fibroblasts from EBA mice were less able to contract collagen gels in vitro; however, addition of TGF-beta1 restored collagen contraction, suggesting an interplay between Flii and TGF-beta1. Elevated Flii gene and protein expression was further observed in the blisters of ColVII hypomorphic mice, a murine model of RDEB, suggesting that reducing Flii in blistered skin could be a potential new approach for treating patients with EB. PMID- 21984128 TI - Serum IgG levels demonstrate seasonal change in connective tissue diseases: a large-scale, 4-year analysis in Japanese. AB - Hypergammaglobulinemia is often found in patients with autoimmune diseases, such as systemic lupus erythematosus (SLE), and its level may correlate with disease activity. However, it is unclear whether immunoglobulin G (IgG) displays seasonal changes. We analyzed the seasonal change in serum IgG by assessing 450 patients with connective tissue disease. The serum IgG levels in summer were compared with those in winter from 2006 to 2009. Independent samples from 355 patients were analyzed to confirm results in the first set. The differences in the IgG levels between the two seasons were analyzed in each disease and compared with disease activity. 488 patients without connective tissue disease were analyzed as reference instead of healthy people as control. We found that connective tissue disease patients tended to show higher levels of serum IgG in summer than in winter every year from 2006 to 2009, whereas patients without connective tissue disease did not demonstrate such a tendency. We observed this seasonal tendency in each disease. Seasonal changes weakly correlated with those of anti-DNA antibody in SLE patients and those of disease activity score in rheumatoid arthritis (RA) patients. Serum IgG levels of patients with connective tissue diseases display seasonal variations. Biological and clinical significance of these variations should be elucidated. PMID- 21984129 TI - Nephrocalcinosis: a rare presenting manifestation of primary Sjogren's syndrome. AB - Renal involvement in primary Sjogren's syndrome (pSS) is not uncommon. Autoimmune tubulointerstitial disorders and distal renal tubular acidosis (dRTA) account for majority of the cases of renal involvement. While dRTA may precede the onset of sicca syndrome in pSS, nephrocalcinosis as a presenting manifestation of pSS is rare. Here, to emphasize the need for initiating investigations for pSS in any patient presenting with nephrocalcinosis due to dRTA, we report a 21-year-old woman presenting with nephrocalcinosis long before pSS was objectively diagnosed. PMID- 21984130 TI - Definitive differences in laboratory and radiological characteristics between two subtypes of juvenile idiopathic arthritis: systemic arthritis and polyarthritis. AB - We performed this study to investigate the differences in radiological and laboratory findings between systemic juvenile idiopathic arthritis (s-JIA) and polyarthritis (p-JIA). Twenty-two patients with s-JIA and 18 with p-JIA were enrolled. Their laboratory findings and radiographs were examined retrospectively. Plain radiographs were obtained before the induction of biological agents. All radiographs were examined for the presence of soft tissue swelling, juxta-articular osteopenia, joint space narrowing, subchondral bone cyst, erosion, epiphyseal irregularity, and growth abnormalities. Carpal length and bone mineral density of the lumbar spine, an indicator of generalized osteoporosis, were also investigated in all the patients enrolled. Laboratory examinations involved white blood cell counts, platelets, C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibody, and matrix metalloproteinase (MMP)-3. Comparisons of the laboratory findings between s-JIA and p-JIA indicated that the titers of anti-CCP antibody and RF were significantly increased in p-JIA sera (P < 0.05). There was no difference in BMD between the two groups of patients. Carpal length was significantly shorter in p-JIA patients than in s-JIA patients (P < 0.05). The most frequent radiological abnormality in s-JIA was juxta-articular osteopenia (93.8%), in comparison to a frequency of 50.0% in p-JIA. Joint space narrowing was shown in 9.8% of the s-JIA patients compared to 35.7% of the p-JIA patients. Subchondral bone cyst and erosion were more frequent in p-JIA than s-JIA. In conclusion, there were differences in radiographic characteristics and laboratory data between s-JIA and p-JIA in this study. In the radiological evaluation, bone related abnormality was prominent in s-JIA and joint-related abnormality was striking in p-JIA, and these results indicated that the pathogenic bases of arthritis appear to differ between these two subtypes of JIA. PMID- 21984131 TI - Cosmetic outcome 1-5 years after breast conservative surgery, irradiation and systemic therapy. AB - The late side-effects of the local therapy of early breast cancer depend on many patient- and therapy-related parameters. We aimed at investigating the factors that influence the cosmetic and functional outcomes among our breast cancer patients after breast-conserving surgery and conformal radiotherapy, with or without adjuvant systemic therapy. A study was made of the association of the cosmetic outcome after a median follow-up time of 2.4 years and the clinical data on 198 patients extracted from a prospectively compiled database. Breast tenderness occurred more frequently among patients <=50 years old (p < 0.05). Long-term side effects were related to radiotherapy-related factors the most, while no effect of the systemic therapy could be detected. The risk of hyperpigmentation, breast edema and breast fibrosis increased by 18%, 23% and 7%, respectively for every 100 cm(3) increase in the irradiated breast volume, while that of breast edema and breast fibrosis increased by 21% and 12%, respectively for every 10 cm(3) increase in the boost volume. Patients who received a photon boost were significantly more likely to develop breast edema and fibrosis than those who received electrons (p < 0.005). Dose inhomogeneity was related to the volume of the irradiated breast (p = 0.037). Dyspigmentation developed more often among patients older than 50 years, while smoking favoured both dyspigmentation and teleangiectasia. Breast edema was related to dyspigmentation (p = 0.003), fibrosis (p < 0.001) and breast asymmetry (p = 0.032), whereas none of these abnormalities were associated with teleangiectasia. Body image changes were more frequent at a younger age (p < 0.005), while the need to change clothing habits occurred more often at an older age (p < 0.05). Radiotherapy-related parameters appear to exert the greatest effect on the overall cosmetic outcome after breast conserving surgery and postoperative radiotherapy. PMID- 21984132 TI - Efficacy and toxicity of CyberKnife re-irradiation and "dose dense" temozolomide for recurrent gliomas. AB - BACKGROUND: Stereotactic radiosurgery (SRS) can be a useful adjunct to the treatment of recurrent glioblastoma multiforme (GBM). Its combination with chemotherapy is attractive for the possible radiosensitization effect and cytotoxicity on tumor cells in distant areas. The aim of this study was to evaluate the efficacy and toxicity of CyberKnife SRS alone and combined with a "dose-dense" administration of temozolomide (TMZ) for recurrent GBM. METHODS: Between July 2007 and July 2010, 23 patients underwent CyberKnife SRS. In 12 patients irradiation was combined with TMZ at 75 mg/m(2)/day for 21 days every 28 days. The median prescription dose in this group was 20 Gy (mean 20.7 +/- 4 Gy) with a median number of fractions of 2. The median dose for the 11 patients who underwent SRS alone was 20 Gy (mean 19.9 +/- 4.4 Gy; p = NS). RESULTS: The median survival was 12 months for patients who underwent SRS/TMZ and 7 months for those who received SRS alone (p < 0.01). The 6-month progression-free survival (PFS) of the SRS/TMZ group was 66.7% vs. 18% for those who underwent SRS alone (p = 0.03). The median time to progression (TTP) was 7 months for patients who underwent SRS/TMZ and 4 months for those who underwent SRS alone (p = 0.01). Corticosteroid dependency was developed by most patients; radionecrosis was evident in one patient (4.3%) receiving TMZ. Grade 3 hematological toxicity was recorded in >40% of patients receiving chemotherapy. CONCLUSIONS: The results suggest that Cyberknife re-treatments are relatively safe using selected dose/fraction schemes. The combination with TMZ improved patients' outcomes with OS and 6-month PFS that favorably compares with alternative treatments, but the incidence of major adverse effects was >40%. Further studies are warranted. PMID- 21984133 TI - Effects of hypoxia on coronary microcirculation during postnatal development. PMID- 21984134 TI - Impact of chronic cyanosis and reoxygenation on the microheterogeneity of the myocardial blood flow: digital radiographic study in neonatal rats. AB - PURPOSE: This study sought to show the heterogeneity of myocardial blood flow in the chronically hypoxic infantile myocardium and its response to reoxygenation using a novel type of digital radiography. METHODS: Newborn rats were housed in a hypoxic chamber or in a normal chamber (controls). After 4 or 8 weeks, the control rats were ventilated with normoxic conditions, and the rats housed under hypoxia were ventilated with either hypoxic (cyanotic group) or normoxic conditions (reoxygenation group). Desmethylimipramine labeled with tritium (HDMI) was injected into the left ventricle, and both ventricular free walls were sectioned and sliced from the subepicardium to the subendocardium at 10 mm thickness. The within-layer distribution of HDMI density was measured by digital radiography, and its spatial heterogeneity (i.e., flow heterogeneity) was quantified by the coefficient of variation (CV) of flows. RESULTS: There were no differences in the CV between the groups in either ventricle at 4 weeks of age and no differences in the right ventricle at 8 weeks of age. There was a trend toward a higher left ventricular CV in the cyanotic group than in the control group at 8 weeks of age (0.637 +/- 0.099 vs. 0.510 +/- 0.060, P = 0.06). At 8 weeks of age, the CV was lower in both ventricles in the reoxygenation group than in those of the control and cyanotic groups. CONCLUSION: The chronically hypoxic infantile myocardium exhibits regional flow heterogeneity similar to that observed in the normal myocardium in both ventricles and exhibits reduced flow heterogeneity in response to reoxygenation. PMID- 21984135 TI - Off-pump coronary artery bypass grafting with an aortic nonclamping technique may reduce the incidence of cerebral complications. AB - PURPOSE: Cerebrovascular accidents after coronary artery bypass grafting (CABG) remain a complication despite the advancements in techniques. Aortic partial clamping should be avoided to prevent this cerebral complication. We use pedicle arterial grafts (bilateral internal-mammary arteries and the right gastroepiploic artery) and saphenous vein graft with a proximal anastomosis device for off-pump CABG without aortic partial clamping. We call this technique the aortic nonclamping technique. METHODS: Between 2001 and 2007, a total of 468 patients underwent coronary bypass operations; 8 who were operated on with cardiopulmonary bypass were excluded from this study. Altogether, 451 patients underwent off-pump CABG using the aortic nonclamping technique. Among the procedures, 354 were performed using pedicle arterial grafts alone, and 99 were done using a saphenous vein graft with a proximal anastomosis device. Nine were performed with aortic partial clamping for any reason. Postoperative cerebral complications, especially cerebral infarction, were analyzed. RESULTS: Cerebral infarction occurred in two cases (0.47%) in the aortic nonclamping group. They were delayed in both cases, one occurring on the third day after operation and the other on the fourth day. One patient in the aortic clamping group had an intraoperative (early) cerebral infarction. CONCLUSION: The aortic nonclamping technique might reduce the incidence of cerebral complications and produce ideal bypass grafts using arterial grafts and saphenous vein grafts with a proximal anastomosis device. PMID- 21984136 TI - Long-term results of total cavopulmonary connection with low ejection fraction. AB - PURPOSE: The aim of this study was to investigate the surgical outcomes and change in cardiac performance after total cavopulmonary connection (TCPC) in patients with reduced ventricular ejection preoperatively. METHODS: Among the 195 patients undergoing TCPC between 1990 and 2001 were 52 who had a preoperative ejection fraction of <=50% (30%-50%, mean 44%). A dominant ventricle was of the morphologically right type in 81% of patients. RESULTS: A total of 9 of the 52 patients died early. Two patients died in the intermediate term. Postoperative exercise testing showed maximum oxygen uptake of 26.4 +/- 5.8 ml/kg/min (anaerobic threshold 18.3 +/- 3.2 ml/kg/ min). The cardiac index was 3.1 +/- 0.9 l/min/m(2) at 1 year after TCPC, with no fundamental change at 5 years (3.1 +/- 0.8 l/min/m(2)). The end-diastolic volume of the dominant ventricle was 130% +/- 74% of the anticipated normal value at 1 year and 93% +/- 27% at 5 years after TCPC, with ejection fractions of 48% +/- 13% and 49% +/- 9%, respectively. When these parameters were plotted for the individual patients, the ejection fraction increased during the first postoperative year, with the percent end-diastolic volume decreasing in 31 survivors; the trend appeared atypical in the remaining 12 survivors. Even in these patients, however, the parameters eventually changed toward favorable circumstances 5 years after TCPC. CONCLUSION: Change in ventricular function was not necessarily pessimistic after TCPC in patients with reduced ventricular contraction preoperatively. PMID- 21984137 TI - Early experience using the da Vinci Surgical System for the treatment of mediastinal tumors. AB - PURPOSE: The da Vinci Surgical System has been used in only a few cases for treating mediastinal tumors in Japan. Recently, we used the da Vinci Surgical System for various types of anterior and middle mediastinal tumors in clinical practice. We report our early experience using the da Vinci Surgical System. METHODS: Seven patients gave written informed consent to undergo robotic surgery for mediastinal tumor dissection using the da Vinci Surgical System. We evaluated the safety and feasibility of this system for the surgical treatment of mediastinal tumors. RESULTS: Two specialists in thoracic surgery who are certified to use the da Vinci S Surgical System and another specialist acted as an assistant performed the tumor dissection. We were able to access difficult-to reach areas, such as the mediastinum, safely. All the resected tumors were classified as benign tumors histologically. The average da Vinci setting time was 14.0 min, the average working time was 55.7 min, and the average overall operating time was 125.9 min. The learning curve for the da Vinci setup and manipulation time was short. CONCLUSION: Robotic surgery enables mediastinal tumor dissection in certain cases more safely and easily than conventional video assisted thoracoscopic surgery and less invasively than open thoracotomy. PMID- 21984138 TI - Prognosis of surgically resected lung cancer with extremely high preoperative serum carcinoembryonic antigen level. AB - PURPOSE: The aim of this study was to investigate the prognosis of resected lung cancer patients with extremely high carcinoembryonic antigen (CEA) levels. Several reports have indicated that increased preoperative serum CEA levels are associated with a dismal outcome after surgery, whereas others have reported long term survival among patients with extremely high preoperative CEA levels. We investigated whether preoperative serum CEA levels, especially extremely high levels, were related to the prognosis of non-small-cell lung cancer (NSCLC) after surgery. METHODS: From September 1996 to January 2008, a total of 649 patients underwent surgical treatment for NSCLC at Juntendo University Hospital. We conducted a retrospective review to investigate the prognostic significance of the preoperative CEA level in these patients. We also investigated the prognosis of patients with an extremely high preoperative CEA level (>30 ng/ml). RESULTS: The 5-year survival rates were 78.4% and 63.0% for patients with normal and abnormal preoperative CEA levels, respectively. The survival rate was significantly worse for patients with abnormal preoperative CEA levels (P = 0.0002). In all, 28 patients had preoperative CEA levels >30 ng/ml. Although most of these patients showed a poor prognosis, 7 (25.0%) were longterm survivors (>4 years). CONCLUSION: An abnormal preoperative CEA level suggests a poor prognosis for patients with NSCLC after surgery. Nevertheless, a few patients with an extremely high preoperative CEA level had long-term survival. Even if the preoperative CEA is extremely high, we perform a careful survey for distant or intrathoracic metastases and should not overlook operable cases. PMID- 21984139 TI - Reports of four surgical treatments of acute pulmonary embolism with a floating thrombus in the right atrium. AB - Acute pulmonary embolism (APE) is a serious disease. Recently, multidetector-row computed tomography (MDCT) has proven to be valuable in detecting APE and deep vein thrombosis. APE is classified as massive, submassive, and nonmassive. The incidence of submassive APE and the number of therapeutic approaches for clinically diagnosed critical submassive APE have both increased. However, most strategies for submassive APE have been conservative, e.g., transvenous catheter pulmonary embolectomy, and there are few reports on surgical pulmonary embolectomy. We examined the surgical outcomes in four cases of submassive APE with a floating thrombus in the right atrium (RA) from August 2003 to July 2008. All patients appeared to have no neurological complications and showed an event free survival of up to 65 months (37 +/- 25 months). Surgical pulmonary embolectomy was effective for submassive APE with a floating thrombus in the RA. PMID- 21984140 TI - Surgical removal of a fractured guidewire entrapped in the coronary artery. AB - We experienced a case with a remnant of a fractured guidewire in the coronary artery. Surgical removal of the total wire by manual traction was unsuccessful. The wire was then cut near the right coronary orifice, and its proximal portion was removed. Cardiac interventionists should recognize that percutaneous coronary intervention is associated with the risk of various cardiovascular accidents. Patients should be informed of such risks. PMID- 21984141 TI - Papillary fibroelastoma of the aortic valve in a beta-thalassemia patient. AB - Papillary fibroelastomas are uncommon benign tumors with frond-like growths usually arising from the heart valves. The identification of their presence is of major clinical importance owing to the fact that although rarely symptomatic they can cause coronary occlusion, stroke, and even sudden cardiac death. We present an asymptomatic 38-year-old woman with homozygous beta-thalassemia in whom transthoracic echocardiography incidentally discovered an aortic mass. Two dimensional echocardiography and magnetic resonance imaging confirmed the diagnosis of papillary fibroelastoma. Valvesparing tumor resection, even in asymptomatic patients, is recommended as the standard therapy procedure. PMID- 21984142 TI - Localized nodular amyloidosis of the lung. AB - Pulmonary localized nodular amyloidosis is a rare disorder and is not associated with primary systemic amyloidosis. We herein report a patient with a growing lung nodule who underwent thoracic surgery and was diagnosed with this condition. This case study suggests that localized nodular amyloidosis should be considered during a differential diagnosis of growing lung nodules and that a histological examination should be performed to distinguish this disorder from lung malignancies. PMID- 21984143 TI - Video-assisted thoracic resection for intralobar pulmonary sequestration. AB - We present a case in which video-assisted thoracic resection for intralobar pulmonary sequestration (ILPS) was successfully performed. A 36-year-old woman had repeated pneumonia. Chest computed tomography (CT) showed a round mass in the right lower lobe of the lung. Subsequent three-dimensional CT revealed that a large anomalous artery arising from the descending thoracic aorta was distributing to the posterior basal segment containing the lesion and was draining into the inferior pulmonary vein. The patient was diagnosed with ILPS and underwent surgery. The anomalous artery was divided, and the sequestered segment was completely resected by video-assisted thoracic surgery (VATS). We think that VATS resection for ILPS is feasible and is a major therapeutic option as noninvasive surgery. PMID- 21984146 TI - [GVHD with GVL separation strategy in allogeneic hematopoietic stem cell transplantation]. PMID- 21984145 TI - Local anesthesia: a strategy for reducing surgical site infections? AB - BACKGROUND: Surgical site infections (SSIs) contribute to increased morbidity, mortality, and hospitalization costs. A previously unidentified factor that may reduce SSIs is the use of local anesthesia. The objective of this study was to determine if the use of local anesthesia is independently associated with a lower incidence of SSIs compared to nonlocal anesthesia. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database (2005 2007), we identified all patients undergoing surgical procedures that could be performed using local or general anesthesia, depending on the preference of the surgeon. Logistic regression was used to identify factors independently associated with the use of local anesthesia. Propensity matching was then used to match local and nonlocal anesthesia cases while controlling for patient and operative characteristics. SSI rates were compared using a chi(2) test. RESULTS: Of 111,683 patients, 1928 underwent local anesthesia; and in 109,755 cases the patients were given general anesthesia where a local anesthetic potentially could have used. In the unmatched analysis, patients with local anesthesia had a significantly lower incidence of SSIs than patients with nonlocal anesthesia (0.7 vs. 1.4%, P = 0.013). Similarly, after propensity matching, the incidence of SSIs in patients given local anesthesia was significantly lower than for that of patients given nonlocal anesthesia (0.8 vs. 1.4%, P = 0.043). CONCLUSIONS: Use of local anesthesia is independently associated with a lower incidence of SSIs. It may provide a safe, simple approach to reducing the number of SSIs. PMID- 21984144 TI - Long-term results of surgery for small intestinal neuroendocrine tumors at a tertiary referral center. AB - BACKGROUND: Small intestinal neuroendocrine tumors (SI-NETs) are uncommon, with an annual incidence of about 1 per 100,000 individuals. The primary tumor (PT) is generally small, but nevertheless the majority of patients have mesenteric lymph node metastases and liver metastases at diagnosis. Our aim was to identify prognostic factors for survival and to evaluate outcome after surgery in SI-NET patients. MATERIAL AND METHODS: We included 603 consecutive patients (325 men; age at diagnosis 63 +/- 11 years [mean +/- SD]) with histopathologically verified SI-NET, who were diagnosed between 1985 and 2010. Hospital charts were reviewed and were scrutinized for carcinoid heart disease (CHD), flush and/or diarrhea, proliferation by Ki-67 index, mesenteric lymph node metastases (m.lgllm), distant abdominal lymph node metastases (da.lgllm), liver tumor load (LTL), extra abdominal metastases (EAM), locoregional resective surgery, as well as debulking of LTL, and adverse events after surgery. RESULTS: Median overall survival (OS) was 8.4 years; 5-year OS was 67%, and 5-year relative survival was 74%. Independent prognostic factors by univariate and multivariate analysis were age at diagnosis, CHD, m.lgllm, da.lgllm, LTL, EAM, peritoneal carcinomatosis (PC), and proliferation. Locoregional resective surgery was associated with increased survival on crude and multivariate analysis. The 30-day mortality in our institution after initial locoregional resective surgery was 0.5% (1/205). CONCLUSIONS: For the first time, m.lgllm and da.lgllm, LTL, PC, and EAM are demonstrated to be independent prognostic factors by multivariate analysis. Locoregional removal of the PT/m.lgllm. was a positive prognostic factor by crude and adjusted analysis and may influence survival. PMID- 21984147 TI - [Effects of mycophenolic acid on human bone marrow-derived mesenchymal stem cells in vitro]. AB - OBJECTIVE: To investigate the effects of mycophenolic acid (MPA) on the proliferation and differentiation of human bone marrow-derived mesenchymal stem cells (MSCs). METHODS: MSCs were treated with MPA at the concentration of 1 MU mol/L, 10 MU mol/L, 50 MU mol/L, and 100 MU mol/L, respectively. Cell proliferation was analyzed using CCK-8 method. Apoptosis was detected by PI/Annexin V assay kit. The mRNA expression of inosine-5'-monophosphate dehydrogenase (IMPDH) in MSCs was analyzed by RT-PCR. Osteogenic differentiation was analyzed by Von Kossa staining, Ca(2+) quantification and real-time PCR. RESULTS: In the range of 1 MU mol/L to 100 MU mol/L, MPA caused a significant subdued proliferation rate of MSCs in a concentration-and time-dependent manner by guanosine depletion, and PI/Annexin staining showed no apoptosis induced by MPA. RT-PCR results showed that MSCs expressed both IMPDH I and IMPDH II. von Kossa staining and Ca(2+) quantification indicated that MPA inhibited osteogenic differentiation of MSCs, and real-time PCR detected a dose-dependent decrease in expression of Osteopontin and BMP-2. Further investigation showed that MPA down regulated the expression of Runx2 and Osterix. CONCLUSION: MPA can inhibit the proliferation of MSCs by guanosine depletion in a concentration-and time dependent manner and inhibit the osteogenic differentiation of MSCs by down regulation of the expression of Runx2 and Osterix. PMID- 21984148 TI - [Effects of blocking inhibitory KIR receptors on cytotoxic activity of human NK cells in vitro]. AB - OBJECTIVE: To investigate the effect of blocking the inhibitory receptors KIR2DL1 and KIR2DL2/2DL3 with monoclonal antibody on cytotoxic activity of human NK cells. METHODS: Human peripheral blood NK cells were isolated by Rosettesep NK sorting kit. The cytotoxic activity of NK cells against human leukemia NB4, K 562, Raji cells and allogeneic mature or dendritic cells (DCs) was detected before or after KIR2DL1 and KIR2DL2/2DL3 were blocked. The effect of NK cells on T lymphocyte proliferation was detected by mixed lymphocyte reaction and TGF beta1 concentration in culture supernatant was measured. RESULTS: The cytotoxicity of NK cells to NB4 cells was augmented with increasing concentration of the antibody. Combination of both antibodies enhanced killing activity of NK cells. NK cells had strong cytotoxicity to K-562 cells, but were not enhanced by the blockade of inhibitory receptors. The cytotoxicity to Raji cells was not evidently augmented. The cytotoxicity of NK cells to mature DC was enhanced remarkably with the increase of concentration of the antibodies (2.20% +/-1.10% compared with 37.59% +/-5.06%, P<0.05). In mixed lymphocyte reaction, the blockade of two antibodies enhanced the inhibition effect of NK cells on T cell proliferation (77.85% +/- 8.31% compared with 43.05% +/- 5.95%, P<0.05) and the content of TGF-beta1 in the supernatant was increased. CONCLUSION: The cytotoxic effects of human NK cells against target cells were significantly enhanced with the blockade of inhibitory KIR receptor; and the cytokine TGF-beta1 secreted by NK cells further inhibits T cells proliferation. PMID- 21984149 TI - [Synergistic cytotoxic effects of rapamycin and idarubicin on human acute T-cell lymphoblastic leukemia Jurkat cells]. AB - OBJECTIVE: To investigate the cytotoxic effects of mTOR inhibitor rapamycin (Rapa) and idarubicin (IDA) on human T-cell acute lymphoblastic leukemia Jurkat cell line. METHODS: The proliferation of Jurkat cells was observed by CCK-8 assay. The combined index was analyzed by Isobologram method. Apoptosis was detected by electron microscopy and flow cytometry with Annexin V/PI staining. Protein expressions of Caspase 3, PARP, Caspase 8, Caspase 9, Akt, p-Akt, P85S6K, p-P85S6K, P70S6K, p-P70S6K, ERK1/2 and p-ERK1/2 were determined by Western blotting. RESULTS: The IC(50) of IDA for Jurkat cells was significantly reduced when combined with 10 nmol/L rapamycin. The combined index was <1. Both electron microscopy and Annexin V/PI staining flow cytometry revealed that rapamycin significantly increased apoptotic sensitivity to IDA. The combination of IDA with rapamycin enhanced the expressions of Caspase 3, PARP, Caspase 8 and Caspase 9. Rapamycin significantly inhibited mTOR signaling upstream Akt and downstream S6K activation triggered by IDA, and the combination of the two agents led to synergistic inhibition of ERK phosphorylation. CONCLUSION: Combination of IDA with rapamycin exerted a synergistic anti-proliferative effect and promoted apoptosis by both extrinsic and intrinsic apoptotic pathways in Jurkat cells. Inhibition of ERK phosphorylation and mTOR signaling by rapamycin may play a certain role in this synergistic effect. PMID- 21984150 TI - [Induction of dendritic cells with multidrug resistance from K562/MDR1 cells]. AB - OBJECTIVE: To induce the differentiation of K562/MDR1 cells into dendritic cells (DC) with multidrug resistance property. METHODS: K562/MDR1 cells and K562 cells were cultured in the presence of GM-CSF and IL-4 to generate DC and matured by TNF-alpha. On d14 K562/MDR1-DC and K562-DC cells were harvested and the expressions of CD1a, CD83, CD80, CD86, HLA-ABC and HLA-DR were assessed by flow cytometry (FCM). The antigen presentation function of K562/MDR1-DC and K562-DC was determined by allogenic mixed lymphocyte reaction (Allo-MLR). The expression of P-glycoprotein and the intracellular accumulation of daunorubicin (DNR) were detected by FCM. The sensitivity of K562/MDR1-DC and K562-DC cell to vincristine, adriamycin was measured using MTT assay. RESULTS: Both K562/MDR1 and K562 cells were differentiated into dendritic cells in the presence of cytokine cocktails, showing the morphologic and immunophenotypic characteristics of DC. K562/MDR1-DC more markedly enhanced proliferation of allogeneic lymphocytes in MLR than K562 DC. High level expression of P-glycoprotein and efflux of DNR were demonstrated in K562/MDR1-DC. K562/MDR1-DC showed multidrug resistance property, with higher IC(50) to VCR and ADM than that of K562-DCs. CONCLUSION: K562/MDR1 cells can be differentiated into DC with the presence of cytokines, the induced K562/MDR1-DC cells express high level of P-glycoprotein and acquire the multidrug resistance property. PMID- 21984151 TI - [TLR4 and organ transplant rejection]. AB - Organ transplant has become one of the strategies for treatment of malignant disease. The transplant-related complications restricted the further development of organ transplantation; graft rejection is most prominent among these complications, which remains a major cause of morbidity and mortality after organ transplant. Toll like receptors 4 (TLR-4) has been shown as a key molecule in innate immunity and immune tolerance. The role of TLR4 in graft rejection after organ transplant is still unknown. This article will review the role and the mechanism of TLR4 to control APC mature, activate T cells, trigger immune attack to organ graft; therefore bring new insights into the pathophysiology of graft rejection and foster the development of new therapies to control graft rejection after organ transplant. PMID- 21984152 TI - [Serial recombinant expression and anti-tumor activity in vitro of antibiotic peptide Alloferon-1]. AB - OBJECTIVE: To generate a recombinant expression system of repeated serial antibiotic peptide Alloferon-1 DNA segment with trypsin digestion site and to determine its anti-tumor activity in vitro. METHODS: A 14 repeated serial DNA segment of Alloferon-1 with a lysine residual at the C-end that acts as the trypsin digestion site was constructed. pET42a vector and E.coli BL21DE3 were applied to generate the prokaryotic expression system of the repeated serial DNA segment of Alloferon-1. The yield of target recombinant product was measured by SDS-PAGE and Bio-Rad Gel image system. Ni-NTA affinity column, trypsin digestion and Sephadex G-50 column were used to purify 14 rAlloferon-1-K fusion protein and rAlloferon-1-K monomer. By using the co-cultivation of BALB/c mouse splenocyte with K562, KB or SGC tumor cells and CCK-8 detection method, the effects of rAlloferon-1-K, chemosynthetic Alloferon-1 (cAlloferon-1) and Alloferon-1-K (cAlloferon-1-K) on the growth and proliferation of tumor cells were detected. RESULTS: The prokaryotic expression system E.coli BL21DE3pET42a-14 Alloferon-1-K efficiently expressed 14 rAlloferon-1-K fusion protein under inducement of IPTG,and the yield of fusion protein was approximate 30% of the total bacterial proteins. 0.1?10 ng/ml rAlloferon-1-K remarkably increased the effect of mouse splenocytes to inhibit the growth and proliferation of K562, KB and SGC cells (P<0.05), and there was no statistically significant difference of the anti-tumor ability of rAlloferon-1-K compared to that of cAlloferon-1 or cAlloferon-1-K (P>0.05). CONCLUSION: A prokaryotic expression system of repeated serial Alloferon-1 DNA segment has been successfully constructed with high yield of rAlloferon-1-K, which maintains anti-tumor activity in vitro. PMID- 21984153 TI - [Anti-proliferation and chemo-sensitization effects of apigenin on human lung cancer cells]. AB - OBJECTIVE: To investigate the antitumor effect of apigenin on human lung cancer cells. METHODS: The anti-proliferation and sensitization effects of apigenin on human lung cancer cells was accessed by counting cells after Trypan blue staining and MTS assay. RESULTS: (1) Apigenin significantly suppressed the proliferation of four types of human lung cancer cells (A549:P=0.041, H460:P=0.050, LTEP a2:P=0.039, H292:P=0.016); (2) Apigenin significantly increased the susceptibility of human lung cancer cells to antitumor drugs (P<0.05 or P<0.01) in a synergistic way (almost all of the combination index values are less than 1). CONCLUSION: Apigenin widely inhibits cell proliferation of various lung cancer cell lines in a dose-dependent manner and the combination treatment of apigenin and antitumor drugs is very effective in human lung cancer cells, and Nrf2-ARE pathway may contribute to the mechanism. PMID- 21984154 TI - [Effects of Mycobacterium tuberculosis on apoptosis of mouse dendritic cells and activation of caspase-3, caspase-8]. AB - OBJECTIVE: To investigate the effects of Mycobacterium tuberculosis on apoptosis of mouse dendritic cells (DC 2. 4) and the activation of caspase-3, caspase-8. METHODS: Mycobacterium tuberculosis H37Rv strain was co-cultured with DC 2. 4 cells. The morphological changes of DC 2. 4 cells were observed with fluorescence microscope after DAPI staining and transmission electron microscope. The apoptosis of DC 2. 4 cells were examined by DNA agarose gel electrophoresis. The activities of caspase-3 and caspase-8 were detected by colorimetric assay. RESULTS: Bacterial invasion was observed while DC 2. 4 cells and H37Rv were co cultured for 2 h; and the rates of invasion were (16.1 +/- 4.3)%, (35.8 +/- 5.1)%, (50.2 +/- 5.7)%, (58.3 +/- 6.2)% and(65.9 +/- 6.9)% at 4, 6, 8,10, 12 h, respectively. The phenomenon of nuclear condensation and marginalization were shown by DAPI staining and transmission electron microscope in DC 2. 4 cells at 6 h of co-cultivation with H37Rv. The characteristic bands of apoptosis by DNA electrophoresis were detected. The activities of caspase-3 and caspase-8 were increased in a time-dependent manner. The rates of DC 2. 4 cell apoptosis were (6.4 +/- 2.5)%, (11.8 +/- 5.3)% and (31.1 +/- 8.7)% at 6 h,12 h and 24 h after co cultivation with H37Rv, respectively. The maximal activities of intracellular caspase-3 and caspase-8 at 10 h and 6 h were (2.01 +/- 0.09) U/MUg and (2.40 +/- 0.07)U/MUg, respectively, which was significantly different compared with the control groups(P<0.05). The activation of caspase-8 was earlier than that of caspase-3. CONCLUSION: Mycobacterium tuberculosis can induce the apoptosis of DC 2. 4 cells, which is associated with the activation of intracellular caspase-3 and caspase-8. PMID- 21984155 TI - [Effects of beta-lactam antibiotics ceftriaxone on expression of glutamate in hippocampus after traumatic brain injury in rats]. AB - OBJECTIVE: To investigate the effect of beta-lactam antibiotics ceftriaxone on the levels of glutamate in hippocampus following traumatic brain injury in rat. METHODS: Rats were divided randomly into three groups:sham group; trauma group and trauma+ceftriaxone group. Rats in the later two groups were subjected to a lateral cortical impact injury caused by a free-falling object, and trauma+ceftriaxone group was treated with ceftriaxone immediately after injury. The levels of glutamate in hippocampus was determined by HPLC at 12 h after trauma; the pathological change at 24 h after trauma was examined and water content of brain tissue at 3, 12 and 24 h after trauma was measured in three groups. RESULTS: Compared with the trauma group,the water content in brain tissue (P<0.05), neuronal death in hippocampus CAl area and the levels of glutamate and aspartate in hippocampus at 12 h (P<0.05) were significantly decreased in trauma+ceftriaxone group. CONCLUSION: beta-lactam antibiotics ceftriaxone can reduce the level of brain glutamate, brain edema and neuronal death after traumatic brain injury in rat. PMID- 21984156 TI - [Effect of venlafaxine on cognitive function and hippocampal brain-derived neurotrophic factor expression in rats with post-stroke depression]. AB - OBJECTIVE: To evaluate the effect of venlafaxine on the cognitive impairment of learning and memory in rats with post-stroke depression (PSD) and to investigate its relationship with the expression of brain-derived neurotrophic factor (BDNF) in hippocampus. METHODS: Fifty male adult SD rats were randomly divided into control group, model group and three treatment groups (5,10, 20 mg*kg(-1) venlafaxine) with ten in each group. After the procedure of selective cerebral right middle artery embolism, a paradigm of continuous 3-week chronic unpredictable mild stress (CUMS) was used to induce PSD. Along with the course of CUMS the peritoneal injection at different dose levels of venlafaxine were performed once a day in PSD rats in a fixed time interval. Morris water maze test was applied to assess the spatial learning and memory function and immunohistochemical staining was used to detect the change of BDNF expression. RESULTS: The learning function decreased significantly in PSD rats compared with the control (P<0.05), as well as in spatial exploring time (14.2 s +/- 4.8 s Compared with 45.9 s +/- 4.5 s) and frequency of spanning platform (1.3 +/- 0.3 Compared with 8.3 +/- 1.1). Moreover,very fewer BDNF positive cells were found in CA3 area of hippocampus in model group in comparison with the control group (9.8 +/- 3.2 Compared with 18.5 +/- 4.7). After different dosage of venlafaxine treatment, the BDNF expression and cognition increased markedly. CONCLUSION: Venlafaxine can improve PSD-induced learning and memory dysfunction, possibly through the enhancement of the BDNF level in the CA3 area of hippocampus. PMID- 21984157 TI - [Effect of hydrogen sulfide-induced delayed preconditioning on glutathione S transferase expression during myocardial ischemia-reperfusion in rats]. AB - OBJECTIVE: To investigate the effect of hydrogen sulfide-induced delayed preconditioning on glutathione S-transferase (GST) expression during myocardial ischemia-reperfusion in rats. METHODS: Sprague-Dawley male rats were randomly divided into 4 groups (n= 10 in each): Group S (sham operation group), Group IR (ischemia/reperfusion group), Group H (IR+ NaHS 0.05 mg/kg iv, 24 h before ischemia) and Groups D receiving IR+NaHS 24 h before ischemia and 5 hydroxydecanoate (5-HD)15 min before ischemia. Animals in groups IR, H and D were subjected to ischemia by 30 min of coronary artery occlusion followed by 2 h of reperfusion. At the end of the reperfusion, myocardial infarct size (IS) was examined. Glutathione S-transferase (GST) was measured by Western blotting. The myocardial ultrastructures were observed under the electron microscopy. RESULTS: The IS was significantly smaller in Group H than that in Group IR [(25.40 +/- 3.54)% compared with (38.27 +/- 5.64)%, P<0.05]. The GST expression in myocardium was significantly higher in Group H than that in Group IR. Microscopic examination showed less myocardial damage in Group H than in Group IR. The protective effects of delayed preconditioning by hydrogen sulfide was prevented by 5-HD pre-treatment. CONCLUSION: The hydrogen sulfide-induced delayed preconditioning attenuates myocardial IR injury possibly through up-regulating glutathione S-transferase expression in rats. PMID- 21984158 TI - [Expression of neural salient serine-/arginine-rich protein 1 (NSSR1) in colorectal cancer]. AB - OBJECTIVE: To investigate the expression of neural salient serine/arginine-rich protein 1 (NSSR1) in colorectal cancer. METHODS: RT-PCR, Western blot and immunohistochemical staining were used to detect the expression of NSSR1 mRNA and protein in different mouse tissues and human colorectal cancer, respectively. RESULTS: NSSR1 mRNA was expressed in mouse cerebrum, cerebellum, heart, liver, intestine, kidney and lung tissue, but NSSR1 protein was only expressed in neural tissues. In normal human intestinal mucosa, NSSR1 was expressed in the colorectal epithelial cells. In colorectal cancer, NSSR1 was highly expressed in the nucleus of tumor cells. CONCLUSION: The extensive expression of NSSR1 in colorectal cancer cells may hint it's roles in the biological function of colorectal cancer. PMID- 21984159 TI - [Effects of 100 Hz sinusoidal vibration on H reflex and M wave in rat soleus muscle following immobilization]. AB - OBJECTIVE: To investigate the effects of 100 Hz sinusoidal vibration on H reflex and M wave in rat soleus muscle following immobilization. METHODS: The immobilization of rat soleus muscle was induced as a disuse muscle model, and 100 Hz sinusoidal vibration was generated by a vibrator and applied to the immobilized soleus muscle, then the changes of H reflex and M wave in muscle were observed after 14 d. RESULTS: Compared to control, after 14 d of immobilization M(max) in soleus muscle decreased (P<0.01), stimulus threshold and S(max) increased (P<0.01); Hmax and H(max)/M(max) decreased (P<0.05, S(max) increased (P<0.05). Compared to immobilized soleus muscle, after 14 d of immobilization with 100 Hz sinusoidal vibration, the M(max) increased(P<0.01), stimulus threshold and S(Mmax) decreased (P<0.05), H(max) (P<0.01) increased and H(max)/M(max) increased (P<0.05). CONCLUSION: 100 Hz sinusoidal vibration plays a significant antagonist role against the changes in H reflex and M wave in rat soleus muscle following immobilization. PMID- 21984160 TI - [Aortic elastic properties and its clinical significance in intracranial aneurysms]. AB - OBJECTIVE: To investigate the aortic elastic properties and its clinical significance in intracranial aneurysms (IAs). METHODS: One hundred and seven IAs patients (57 with hypertension) and 108 healthy subjects were recruited. The internal aortic diameters in systole and diastole were measured by the M-mode echocardiography, the aortic elasticity indexes were calculated and compared. RESULTS: The aortic distensibility (DIS) was lower and the aortic stiffness index (SI) was higher in IAs patients than those in controls (both P <0.001). DIS was lower and SI was higher in IAs patients with hypertension (IAs-HP) than those in IAs with no hypertension (P <0.001). Similar results were obtained when the aortic elasticity index were adjusted for body surface area and body mass index. CONCLUSION: Abnormal aortic elasticity is a common finding in IAs patients and hypertension is closely related to the severity of aortic elasticity. PMID- 21984161 TI - [Clinical and genetic analysis of a pedigree of Kennedy disease]. AB - OBJECTIVE: To review the clinical and genetic features of a pedigree of Kennedy disease in China. METHODS: The clinical data of patients from a Kennedy disease family were collected. The numbers of trinucleotide CAG repeats in exon 1 of the androgen receptor gene were determined by DNA sequencing and repeat fragment analysis. RESULTS: In the pedigree, 4 patients were identified as Kennedy disease. Clinical manifested with adult-onset, progressive proximal limb muscle weakness and atrophy, gynecomastia, oligospermia were also presented. The number of trinucleotide CAG repeats in exon 1 of the androgen receptor gene was 51 in the proband. The electrophysiological study showed sensory and motor involvement and their serum triglycerides values were elevated significantly. CONCLUSION: Androgen receptors gene testing is the most reliable diagnosing method, the patients suspected as Kennedy disease should have a gene testing of androgen receptors. PMID- 21984162 TI - [HIF-1 signal pathway in cellular response to hypoxia]. AB - HIF-1 is composed of HIF-1alpha and HIF-1beta subunits. It promotes target genes transcription under hypoxia and plays essential roles in cell development, physiological adaptations, and pathological processes. In the past 10 years, the research on signaling pathways of HIF-1 in response to cell hypoxia stress, especially on HIF-1alpha-mediated gene transcription has made great progress. PMID- 21984163 TI - [Polysaccharides activate signaling pathways of macrophage]. AB - Polysaccharides extracted from various sources are natural active substances, which may lead to the activation of macrophage via multiple pathways and mechanisms. This article intends to illustrate the signaling pathways of polysaccharides from plants, fungi, algae and other sources, to identify the mechanisms on the molecular level, and to explore the novel target immunomodulatory agents. PMID- 21984164 TI - [Laparoscopic multi-point tie MESH repair of white line hernia: a case report]. PMID- 21984166 TI - Effects of fall conditions and biological variability on the mechanism of skull fractures caused by falls. AB - In a forensic investigation, there is considerable difficulty in distinguishing between different mechanisms that could explain the head injury sustained. The key question is often whether the injury was the consequence of a fall, a blow, or a fall caused by a blow. Better understanding of the parameters influencing the mechanism of skull fracture could be of use when attempting to distinguish between different causes of injury. Numerous parameters concerning fall conditions and biological variability are reported in the literature to influence the mechanism of skull fracture. At the current time, there are no studies that investigate both the effect of a fall and biological parameters. The aim of this paper is to study the influence of these parameters on the mechanism of skull fracture using a numerical approach. We focused on accidental falls from a standing height. A multibody model was used to estimate head impact velocities and a finite element model was used to investigate the effect of the fall conditions and of biological variability on skull fracture. The results show that the mechanism of skull fractures is influenced by a combination of at least four parameters: impact velocity, impact surface, cortical thickness and cortical density. PMID- 21984167 TI - Wound ballistic evaluation of the Taser(r) XREP ammunition. AB - The Taser(r) eXtended Range Electronic Projectile (XREP(r)) is a wireless conducted electrical weapon (CEW) designed to incapacitate a person from a larger distance. The aim of this study was to analyze the ballistic injury potential of the XREP. Twenty rounds were fired from the Taser(r)X12 TM shotgun into ballistic soap covered with artificial skin and clothing at different shooting distances (1 25 m). One shot was fired at pig skin at a shooting distance of 10 m. The average projectile velocity was 67.0 m/s. The kinetic energy levels on impact varied from 28-52 J. Depending on the intermediate target, the projectiles penetrated up to 4.2 cm into the ballistic soap. On impact the nose assembly did not separate from the chassis, and no electrical activation was registered. Upon impact, a skin penetration of the XREP cannot be excluded. However, it is very unlikely at shooting distances of 10 m or more. Clothing and a high elasticity limit of the target body area can significantly reduce the penetration risk on impact. PMID- 21984168 TI - Electronic structures and thermochemical properties of the small silicon-doped boron clusters B(n)Si (n=1-7) and their anions. AB - We perform a systematic investigation on small silicon-doped boron clusters B(n)Si (n=1-7) in both neutral and anionic states using density functional (DFT) and coupled-cluster (CCSD(T)) theories. The global minima of these B(n)Si(0/-) clusters are characterized together with their growth mechanisms. The planar structures are dominant for small B(n)Si clusters with n<=5. The B(6)Si molecule represents a geometrical transition with a quasi-planar geometry, and the first 3D global minimum is found for the B(7)Si cluster. The small neutral B(n)Si clusters can be formed by substituting the single boron atom of B(n+1) by silicon. The Si atom prefers the external position of the skeleton and tends to form bonds with its two neighboring B atoms. The larger B(7)Si cluster is constructed by doping Si-atoms on the symmetry axis of the B(n) host, which leads to the bonding of the silicon to the ring boron atoms through a number of hyper coordination. Calculations of the thermochemical properties of B(n)Si(0/-) clusters, such as binding energies (BE), heats of formation at 0 K (DeltaH(f)(0)) and 298 K (DeltaH(f)([298])), adiabatic (ADE) and vertical (VDE) detachment energies, and dissociation energies (D(e)), are performed using the high accuracy G4 and complete basis-set extrapolation (CCSD(T)/CBS) approaches. The differences of heats of formation (at 0 K) between the G4 and CBS approaches for the B(n)Si clusters vary in the range of 0.0-4.6 kcal mol(-1). The largest difference between two approaches for ADE values is 0.15 eV. Our theoretical predictions also indicate that the species B(2)Si, B(4)Si, B(3)Si(-) and B(7)Si(-) are systems with enhanced stability, exhibiting each a double (sigma and pi) aromaticity. B(5)Si(-) and B(6)Si are doubly antiaromatic (sigma and pi) with lower stability. PMID- 21984165 TI - Postmortem chemistry update part II. AB - As a continuation of "Postmortem Chemistry Update Part I," Part II deals with molecules linked to liver and cardiac functions, alcohol intake and alcohol misuse, myocardial ischemia, inflammation, sepsis, anaphylaxis, and hormonal disturbances. A very important array of new material concerning these situations had appeared in the forensic literature over the last two decades. Some molecules, such as procalcitonin and C-reactive protein, are currently researched in cases of suspected sepsis and inflammation, whereas many other analytes are not integrated into routine casework. As in part I, a literature review concerning a large panel of molecules of forensic interest is presented, as well as the results of our own observations, where possible. PMID- 21984170 TI - Interfacial mechanisms governing cyclopentane clathrate hydrate adhesion/cohesion. AB - The present work uses a micromechanical force apparatus to directly measure cyclopentane clathrate hydrate cohesive force and hydrate-steel adhesive force, as a function of contact time, contact force and temperature. We present a hydrate interparticle force model, which includes capillary and sintering contributions and is based on fundamental interparticle force theories. In this process, we estimate the cyclopentane hydrate tensile strength to be approximately 0.91 MPa. This hydrate interparticle force model also predicts the effect of temperature on hydrate particle cohesion force. Finally, we present the first direct measurements of hydrate cohesive force in the gas phase to be 9.1 +/ 2.1 mN/m at approximately 3 degrees C (as opposed to 4.3 +/- 0.4 mN/m in liquid cyclopentane). PMID- 21984169 TI - Combination effects of sodium butyrate and pyridoxine treatment on cell proliferation and neuroblast differentiation in the dentate gyrus of D-galactose induced aging model mice. AB - We previously reported that sodium butyrate (SB), a histone deacetylase inhibitor, robustly increased pyridoxine-induced cell proliferation and neuroblast differentiation in the dentate gyrus of the adult mouse. In this study, we investigated the effects of treatment with SB combined with pyridoxine on cell proliferation and neuroblast differentiation in the dentate gyrus of a mouse model of aging induced by D: -galactose (D: -gal). D: -gal was administered to 20-week-old male mice (D: -gal mice) for 10 weeks to induce changes that resemble natural aging in animals. Seven weeks after D: -gal (100 mg/kg) treatment, vehicle (physiological saline; D: -gal-vehicle mice) and SB (300 mg/kg) combined with pyridoxine (Pyr; 350 mg/kg) were administered to the mice (D: -gal-Pyr-SB mice) for 3 weeks. Escape latency under water maze in the D: -gal mice was longer than that in the control mice. In the D: -gal-Pyr-SB mice, escape latency was similar to that in the control mice. In the D: -gal mice, many cells in the granule cell layer of the dentate gyrus showed pyknosis and condensation of the cytoplasm. However, in the D: -gal-Pyr-SB mice, such cellular changes were rarely found. Furthermore, the D: -gal mice showed a great reduction in cell proliferation (Ki67-positive cells) and neuroblast differentiation (doublecortin positive neuroblasts) in the dentate gyrus compared to control mice. However, in the D: -gal-Pyr-SB mice, cell proliferation and neuroblast differentiation were markedly increased in the dentate gyrus. Furthermore, the administration of pyridoxine with sodium butyrate significantly increased Ser133-phosphorylated cyclic AMP response element binding protein in the dentate gyrus. These results indicate that the combination treatment of Pyr with SB in D: -gal mice ameliorated the D: -gal-induced reduction in cell proliferation, neuroblast differentiation, and memory deficits. PMID- 21984171 TI - Cognitive impairment following cardiopulmonary bypass: strategies for its prevention. PMID- 21984172 TI - New treatment options for atrial fibrillation: towards patient tailored therapy. PMID- 21984173 TI - Pregnancy in congenital and valvular heart disease. PMID- 21984176 TI - Order parameter dependence of the viscosity coefficients of a biaxial nematic liquid crystal. AB - We derive expressions for the order parameter dependence of the viscosity coefficients of a biaxial nematic liquid crystal by comparing its dissipation function expressed in terms of directors with that expressed in terms of order tensors. The results enable us to identify the dominant flow viscosity coefficients and to compare their temperature variation according to their dependence on the dominant scalar order parameters. By considering different orientations of an external field, we identify three characteristic switching times corresponding to three rotational viscosities, and we estimate the ratio of the switching times of the primary and the secondary directors. PMID- 21984177 TI - A simple molecular theory for photo-induced smectic phase. AB - The response of liquid crystals to light is very important for applications of liquid crystals in display and memory devices. Recently experiments have been carried out on liquid crystals doped with photoactive azo compounds. It is seen that UV rays incident on such systems can lower the nematic isotropic transition temperature T (NI). Also, in some mixtures, a photo-induced smectic phase is observed. This is attributed to the change in the trans (longer) isomer to cis (shorter) isomer of the photoactive dopant. We have earlier developed a molecular mean-field model assuming the medium to consist of inter-converting anti-parallel and parallel pairs to explain the molecular origin of "two lengths". The model was used to explain double re-entrance, the effect of electric field on T (NI), etc. This model is modified to include the change of trans to cis isomer which is equivalent to an increase of fraction of parallel (shorter) pairs. The calculated phase diagram with respect to incident UV radiation energy shows an induced smectic phase. This is in qualitative agreement with experimental trends. PMID- 21984178 TI - Efficiency of pseudo-spectral algorithms with Anderson mixing for the SCFT of periodic block-copolymer phases. AB - This study examines the numerical accuracy, computational cost, and memory requirements of self-consistent field theory (SCFT) calculations when the diffusion equations are solved with various pseudo-spectral methods and the mean field equations are iterated with Anderson mixing. The different methods are tested on the triply periodic gyroid and spherical phases of a diblock-copolymer melt over a range of intermediate segregations. Anderson mixing is found to be somewhat less effective than when combined with the full-spectral method, but it nevertheless functions admirably well provided that a large number of histories is used. Of the different pseudo-spectral algorithms, the 4th-order one of Ranjan, Qin and Morse performs best, although not quite as efficiently as the full-spectral method. PMID- 21984179 TI - Continuous direct spinning of fibers of single-walled carbon nanotubes with metallic chirality. PMID- 21984180 TI - Responses to positive affect predict mood symptoms in children under conditions of stress: a prospective study. AB - Rumination to negative affect has been linked to the onset and maintenance of mood disorders in adults as well as children. Responses to positive affect have received far less attention thus far. A few recent studies in adults suggest that responses to positive affect are involved in the development of both depressive and hypomanic symptoms, but thus far no study has investigated their role in childhood mood problems. The purpose of the present study was to validate a child version of the Responses to Positive Affect questionnaire and examine the extent to which responses to positive affect prospectively predict mood symptoms over a 3-month interval. The Responses to Positive Affect questionnaire for Children was found to assess two types of responses to positive affect: Positive Rumination and Dampening. Both subscales showed sufficient internal consistency and moderate stability over a 3-month interval. Low levels of positive rumination and high levels of dampening were concurrently associated with depressive symptoms, over and above responses to negative affect. Importantly, low levels of positive rumination also predicted increases in depressive symptoms over a 3-month interval over and above baseline symptoms in children reporting high levels of stress. Both positive rumination and dampening were positively related to concurrent hypomanic symptoms and high levels of positive rumination predicted increases in hypomanic symptoms over a 3-month interval over and above baseline symptoms in children reporting high levels of stress. The results underscore the added value of assessing responses to positive affect in addition to responses to negative affect. PMID- 21984181 TI - Interaction of HIF and USF signaling pathways in human genes flanked by hypoxia response elements and E-box palindromes. AB - Rampant activity of the hypoxia-inducible factor (HIF)-1 in cancer is frequently associated with the malignant progression into a harder-to-treat, increasingly aggressive phenotype. Clearly, anti-HIF strategies in cancer cells are of considerable clinical interest. One way to fine-tune, or inhibit, HIF's transcriptional outflow independently of hydroxylase activities could be through competing transcription factors. A CACGTG-binding activity in human hepatoma cells was previously found to restrict HIF's access to hypoxia response cis elements (HRE) in a Daphnia globin gene promoter construct (phb2). The CACGTG factor, and its impact on hypoxia-responsive human genes, was analyzed in this study by genome-wide computational scans as well as gene-specific quantitative PCR, reporter and DNA-binding assays in hepatoma (Hep3B), cervical carcinoma (HeLa), and breast carcinoma (MCF7) cells. Among six basic helix-loop-helix transcription factors known to target CACGTG palindromes, we identified upstream stimulatory factor (USF)-1/2 as predominant phb2 CACGTG constituents in Hep3B, HeLa, and MCF7 cells. Human genes with adjacent or overlapping HRE and CACGTG motifs included with lactate dehydrogenase A (LDHA) and Bcl-2/E1B 19 kDa interacting protein 3 (BNIP3) hypoxia-induced HIF-1 targets. Parallel recruitment of HIF-1alpha and USF1/2a to the respective promoter chromatin was verified for all cell lines investigated. Mutual complementing (LDHA) or moderating (BNIP3) cross-talk was seen upon overexpression or silencing of HIF-1alpha and USF1/2a. Distinct (LDHA) or overlapping (BNIP3) promoter-binding sites for HIF-1 and USFs were subsequently characterized. We propose that, depending on abundance or activity of its protein constituents, O(2)-independent USF signaling can function to fine-tune or interfere with HIF-mediated transcription in cancer cells. PMID- 21984182 TI - alphaB-crystallin, an effector of unfolded protein response, confers anti-VEGF resistance to breast cancer via maintenance of intracrine VEGF in endothelial cells. AB - Effective inhibition of angiogenesis targeting the tumor endothelial cells requires identification of key cellular and molecular mechanisms associated with survival of vasculatures within the tumor microenvironment. Intracellular autocrine (intracrine) VEGF production by endothelial cells plays a critical role on the vasculature homeostasis. In vitro breast cancer cell-stimulated activation of the unfolded protein response (UPR) of the endothelial cells contributes to maintenance of the intracrine VEGF levels in the endothelial cells through the upregulation of a previous undescribed downstream effector- alphaB-crystallin (CRYAB). siRNA-mediated knockdown of two major UPR proteins-inositol requiring kinase 1 and ATF6, led to attenuated CRYAB expression of the endothelial cells. Finally, inhibition of CRYAB blocked the breast cancer cell-stimulated increase in the endogenous VEGF levels of the endothelial cells. A VEGF limited proteolysis assay further revealed that CRYAB protected VEGF for proteolytic degradation. Here, we report that the molecular chaperone-CRYAB was significantly increased and colocalized with tumor vessels in a breast cancer xenograft. Specifically, neutralization of VEGF induced higher levels of CRYAB expression in the endothelial cells cocultured with MDA-MB-231 or the breast cancer xenograft with a significant survival benefit. However, knockdown of CRYAB had a greater inhibitory effect on endothelial survival. These findings underscore the importance of defining a role for intracrine VEGF signaling in sustaining aberrant tumor angiogenesis and strongly implicate UPR/CRYAB as dichotomous parts of a crucial regulation pathway for maintaining intracrine VEGF signaling. PMID- 21984183 TI - Patient characteristics of deceased organ donors in Switzerland 1998-2008. AB - BACKGROUND: Transplantation today faces two major issues: organ shortage, and the increasing age of deceased donors. The former leads to growing waiting lists and, as a consequence, to a higher mortality of patients in need of an organ. The latter results in an augmentation of the proportion of organs from so called extended criteria donors, which, in the past, have been associated with inferior outcomes. METHODS: Retrospective analysis of the patient characteristics of all deceased organ donors in Switzerland from 1 January 1998 to 31 December 2008. A total of 1004 patient records of brain-dead organ donors (59.4% male, 40.6% female) were analysed for demographic data and causes of death. RESULTS: The average donor age increased from 43.8 +/- 16.9 years in 1998 to 51.7 +/- 18.0 years in 2008 (+27.6%; p <0.05). When comparing 2008 with 1998, cerebral haemorrhage accounts for 52.8% of the causes of death in 2008 (+16.7 percentage points), whereas the proportion of cranio-cerebral trauma decreased by 22 percentage points to 16.9%. The largest group of donors are the 16-55 year-olds with a 50% quota in 2008 (-23.6% compared with 1998). During the study period, the >=65 year-old group had a 216.2% growth rate, and it accounts 26.6% of the donors in 2008 (p <0.05). CONCLUSIONS: A shift in the causes of death significantly increased the average age of donors, and transplantation medicine is confronted with a growing number of extended criteria donors. Nevertheless, 10 year survival of transplant recipients is better than ever before. PMID- 21984184 TI - miRNA repression involves GW182-mediated recruitment of CCR4-NOT through conserved W-containing motifs. AB - miRNA-mediated repression in animals is dependent on the GW182 protein family. GW182 proteins are recruited to the miRNA repression complex through direct interaction with Argonaute proteins, and they function downstream to repress target mRNA. Here we demonstrate that in human and Drosophila melanogaster cells, the critical repressive features of both the N-terminal and C-terminal effector domains of GW182 proteins are Gly/Ser/Thr-Trp (G/S/TW) or Trp-Gly/Ser/Thr (WG/S/T) motifs. These motifs, which are dispersed across both domains and act in an additive manner, function by recruiting components of the CCR4-NOT deadenylation complex. A heterologous yeast polypeptide with engineered WG/S/T motifs acquired the ability to repress tethered mRNA and to interact with the CCR4-NOT complex. These results identify previously unknown effector motifs functioning as important mediators of miRNA-induced silencing in both species, and they reveal that recruitment of the CCR4-NOT complex by tryptophan-containing motifs acts downstream of GW182 to repress mRNAs, including inhibiting translation independently of deadenylation. PMID- 21984185 TI - miRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT. AB - miRNAs recruit the miRNA-induced silencing complex (miRISC), which includes Argonaute and GW182 as core proteins. GW182 proteins effect translational repression and deadenylation of target mRNAs. However, the molecular mechanisms of GW182-mediated repression remain obscure. We show here that human GW182 independently interacts with the PAN2-PAN3 and CCR4-NOT deadenylase complexes. Interaction of GW182 with CCR4-NOT is mediated by two newly discovered phylogenetically conserved motifs. Although either motif is sufficient to bind CCR4-NOT, only one of them can promote processive deadenylation of target mRNAs. Thus, GW182 serves as both a platform that recruits deadenylases and as a deadenylase coactivator that facilitates the removal of the poly(A) tail by CCR4 NOT. PMID- 21984186 TI - Two classes of silencing RNAs move between Caenorhabditis elegans tissues. AB - Organism-wide RNA interference (RNAi) is due to the transport of mobile silencing RNA throughout the organism, but the identities of these mobile RNA species in animals are unknown. Here, we present genetic evidence that both the initial double-stranded RNA (dsRNA), which triggers RNAi, and at least one dsRNA intermediate produced during RNAi can act as or generate mobile silencing RNA in C. elegans. This dsRNA intermediate requires the long dsRNA-binding protein RDE 4, the endonuclease DCR-1, which cleaves long dsRNA into double-stranded short interfering RNA (ds-siRNA), and the putative nucleotidyltransferase MUT-2 (RDE 3). However, single-stranded siRNA and downstream secondary siRNA produced upon amplification by the RNA-dependent RNA polymerase RRF-1 do not generate mobile silencing RNA. Restricting intertissue transport to long dsRNA and directly processed siRNA intermediates rather than amplified siRNA may serve to modulate the extent of systemic silencing in proportion to available dsRNA. PMID- 21984187 TI - Effect of phospholipid bilayer phase asymmetry on phospholipase d reaction induced vesicle rupture. AB - Spherical phospholipid bilayers, vesicles, were formed with respect to phase of each layer via a double emulsion technique. At the outer layer of the vesicles, phospholipase D catalyzed for the conversion of phosphatidylcholine (PC) to phosphatidic acid (PA). The reaction caused by phospholipase D (PLD) induced a curvature change in the vesicles, which eventually led them to rupture. Response time from the PLD injection to the rupture was monitored for the phase of each layer by using fluorescence intensity changes of pH-sensitive dye encapsulated in the vesicles. It was found that low ionic strength and asymmetric phase retarded response time. The retardation seems to be related to the stability of the vesicles, which is due to the interaction between the lipid molecules. In the liquid phases of the outer lipid layers, the unexpected slow response time may be attributed either to the fast lateral diffusion, which relieves the curvature change of the vesicles, or to the low concentration of PCs, which are less for the reaction compared to the solid phase of the outer lipid layer, rather than the stability. PMID- 21984188 TI - The diversity of protein turnover and abundance under nitrogen-limited steady state conditions in Saccharomyces cerevisiae. AB - To establish more advanced models of molecular dynamics within cells, protein characteristics such as turnover rate and absolute instead of relative abundance have to be analyzed. We applied a proteomics strategy to analyze protein degradation and abundance in Saccharomyces cerevisiae. We used steady-state chemostat cultures to ascertain well-defined growth conditions and nitrogen limited media, which allowed us to rapidly switch from (14)N to (15)N-isotope containing media and to monitor the decay of the (14)N mono-isotope signals in time. We acquired both protein abundance information and degradation rates of 641 proteins. Half-lives of individual proteins were very diverse under nitrogen limited steady-state conditions, ranging from less than 30 min to over 20 h. Proteins that act as single physical complexes do not always show alike half lives. For example the chaperonin-containing TCP-1 complex showed similar intermediate half-lives ranging from 7 to 20 h. In contrast, the ribosome exhibited a wide diversity of half-lives ranging from 2.5 to over 20 h, although their cellular abundances were rather similar. The stabilities of proteins involved in the central sugar metabolism were found to be intermediary, except for the glycolytic enzymes Hxk1p and Fba1p and the TCA-cycle proteins Lsc2p and Kgd1p, which showed half-lives of over 20 h. These data stress the need for inclusion of quantitative data of protein turn-over rates in yeast systems biology. PMID- 21984189 TI - ApoE gene polymorphism and vascular dementia in Chinese population: a meta analysis. AB - Vascular dementia is the second common cause of dementia, only second to Alzheimer's disease in later life. The Apolipoprotein E (ApoE) gene polymorphism as a risk factor in vascular dementia has been suggested, but direct evidence from genetic association studies remains inconclusive even in Chinese population. Therefore, we performed this meta-analysis in order to evaluate the relationship between ApoE gene polymorphism and susceptibility to vascular dementia in Chinese population by pooling data from all relevant case-control studies published domestically and abroad from January 1990 to May 2011. 18 case-control studies were selected. Meta-analysis results showed that the pooled OR value of vascular dementia subjects in Chinese population with epsilon4 allele carriers was 2.07 [95% CI (1.69, 2.53)], and the pooled OR value of vascular dementia subjects with E4/E4 genotype was 3.34 [95% CI (1.89, 5.88)]. These results suggest that ApoE polymorphism is significantly associated with susceptibility to vascular dementia in Chinese population. The subject with at least one epsilon4 allele or E4/E4 genotype has higher risk suffering from vascular dementia than others. PMID- 21984190 TI - CHA(2)DS(2)-VASc score and prognosis in ischemic strokes with atrial fibrillation. AB - The CHA(2)DS(2)-VASc score was developed to improve stroke risk stratification in atrial fibrillation (AF) patients. We sought to analyze the distribution and prognostic value of the CHA(2)DS(2)-VASc score in a cohort of ischemic stroke patients with AF. In total, 439 consecutive stroke patients with AF were studied. The CHA(2)DS(2)-VASc score was calculated according to clinical status before stroke onset. Poor outcome was defined as a modified Rankin score of 3 to 6 at 3 months. Association between CHA(2)DS(2)-VASc score and poor outcome was analyzed using logistic regression analysis. In 95.6% of patients, CHA(2)DS(2)-VASc was >1 and only 41.8% of those with previously diagnosed AF were using oral anticoagulation at the time of the stroke. Poor outcome was found in 53.1% of the patients. In univariate analysis age, female sex, current smoking, previous stroke, CHA(2)DS(2)-VASc score, and stroke severity were associated with outcome. In multivariate analysis, CHA(2)DS(2)-VASc score was independently associated with poor outcome [OR 1.36 (95% CI: 1.14-1.62), P = 0.001] as well as NIHSS [OR 1.22 (95% CI: 1.17-1.26), P < 0.001]. After removing stroke severity, therapeutic anticoagulation was also associated with stroke prognosis [OR 0.45 (95% CI: 0.23 0.86), P = 0.016]. Most patients with ischemic stroke and AF have a high CHA(2)DS(2)-VASc score. Independent of stroke severity, CHA(2)DS(2)-VASc score is associated with 3-month outcome. Despite all the available information and guidelines, our AF patients are clearly undertreated. PMID- 21984191 TI - Case-control study of blink rate in Parkinson's disease under different conditions. AB - Standard neurology texts list a reduced blink rate as one of the clinical features of Parkinson's disease. However, there are few clinical studies which have quantified this clinical sign. Here we present the results of a quantified study in a cohort of cases and controls using a standard protocol. Cases meeting standard criteria for a diagnosis of Parkinson's disease were studied together with age- and sex-matched controls. Baseline data included age, sex, duration of disease, Hoehn and Yahr stage, mini-mental state examination and treatment. Subjects were videoed undertaking three different tasks: being interviewed, watching a video, and reading from a book. Blink rates were calculated as a mean 'per minute' figure for each of the three tasks. A meta-analysis of previous studies of blink rate was undertaken. A total of 20 cases and 41 controls were studied. A decline in blink rate with increasing age was seen for cases but not controls. A significant reduction in blink rate was seen in cases when compared with controls for each of the test conditions. Blink rates were highest in subjects when being interviewed and were lowest whilst reading a passage in both cases and controls. No effect of disease duration, severity or treatment was observed. We have quantified the reduction in blink rate which has long been recognised as a feature of Parkinson's disease. We have identified factors which determine blink rate within individuals. We have also been able to define normal and abnormal levels for blink rate which may be of value clinically and for future research. PMID- 21984192 TI - Conjugate downward and upward vertical gaze palsy due to unilateral rostral midbrain infarction. PMID- 21984193 TI - Autoimmunity as a prognostic factor in sporadic adult onset cerebellar ataxia. AB - Cerebellar adult onset ataxia is a heterogeneous condition. The aim of this study was to ascertain if there is a heightened autoimmune background in patients with sporadic cerebellar ataxia of unknown origin, and if autoimmunity correlates with a more rapid evolution of the ataxia. We selected patients with sporadic progressive adult onset cerebellar ataxia with a follow-up of >5 years. As controls we included 43 patients with genetically demonstrated hereditary ataxia. All patients were tested for a panel of neuronal (onconeuronal, glutamate decarboxylase [GAD], IgG/IgA transglutaminase 6 antibodies) and systemic non neuronal antibodies (including IgG/IgA gliadin and transglutaminase 2, thyroperoxidase, thyroglobulin, antinuclear, striational, smooth muscle, mitochondrial, liver kidney microsomal, and parietal gastric cells antibodies). Correlation between the antibodies and disease progression was studied with Cox regression models and Kaplan-Meier plots. Forty-four patients were included. All patients were negative for onconeuronal or GAD antibodies. There were no significant differences between patients and controls in the prevalence of transglutaminase 6, 2, gliadin, or thyroid antibodies. However, when we studied the panel of systemic non-neuronal autoantibodies as a group, antibodies were more frequent in patients with sporadic ataxia (p = 0.018). The presence of one or more systemic non-neuronal antibodies correlated with a faster evolution to stage 2 (loss of independent gait) (p = 0.03) and shorter survival (p = 0.03) in patients with sporadic ataxia. We conclude that there is probably a heightened autoimmune background in some patients with sporadic cerebellar ataxia of unknown origin. The presence of systemic non-neuronal autoantibodies is a prognostic marker. PMID- 21984195 TI - Multiple abdominal peritoneal and intestinal variations and their accompanying clinical implications. AB - Accessory peritoneal sac and cystoduodenal ligament as peritoneal variations were observed in a cadaver in our laboratory. Slender stomach, thin transverse colon, redundant sigmoid colon, absent ascending colon and doubly distended gall bladder were also reported in the same cadaver. Relevant anatomical and clinical implications are discussed. PMID- 21984194 TI - Needs assessment of cancer survivors in Connecticut. AB - INTRODUCTION: There are knowledge gaps regarding the needs of cancer survivors in Connecticut and their utilization of supportive services. METHODS: A convenience sample of cancer survivors residing in Connecticut were invited to complete a self-administered (print or online) needs assessment (English or Spanish). Participants identified commonly occurring problems and completed a modified version of the Supportive Care Needs Survey Short Form (SNCS-SF34) assessing needs across five domains (psychosocial, health systems/information, physical/daily living, patient care /support, and sexuality). RESULTS: The majority of the 1,516 cancer survivors (76.4%) were women, 47.5% had completed high school or some college, 66.1% were diagnosed <=5 years ago, and 87.7% were non-Hispanic white. The breast was the most common site (47.6%), followed by the prostate, colorectal, lung, and melanoma. With multivariate adjustment, need on the SCNS-SF34 was greatest among women, younger survivors, those diagnosed within the past year, those not free of cancer, and Hispanics/Latinos. We also observed some differences by insurance and education status. In addition, we assessed the prevalence of individual problems, with the most common being weight gain/loss, memory changes, paying for care, communication, and not being told about services. CONCLUSIONS: Overall and domain specific needs in this population of cancer survivors were relatively low, although participants reported a wide range of problems. Greater need was identified among cancer survivors who were female, younger, Hispanic/Latino, and recently diagnosed. IMPLICATIONS FOR CANCER SURVIVORS: These findings can be utilized to target interventions and promote access to available resources for Connecticut cancer survivors. PMID- 21984196 TI - Tracheal dimensions in human fetuses: an anatomical, digital and statistical study. AB - PURPOSE: Rapid advances in perinatal medicine have resulted in increased number of various tracheo-bronchial interventions on fetal and neonatal airways. The present study was performed to compile normative data for external dimensions of the trachea at varying gestational age. MATERIALS AND METHODS: Using anatomical dissection, digital image analysis (NIS-Elements BR 3.0) and statistical analysis (ANOVA, regression analysis), a range of measurements (prebifurcation and bifurcation lengths, proximal and distal external transverse diameters, proximal external cross-sectional area, and external volume) for the trachea in 73 spontaneously aborted fetuses (39 male, 34 female) aged 14-25 weeks was examined. RESULTS: No significant male-female differences were found (P > 0.05). The prebifurcation and bifurcation lengths ranged from 8.14 +/- 1.90 to 20.77 +/- 0.50 mm and from 2.23 +/- 0.25 to 5.77 +/- 0.76 mm, according to the functions y = -54.291 + 23.940 * ln (Age) +/- 1.681 (R (2) = 0.78) and y = -10.756 + 4.860 * ln (Age) +/- 0.731 (R (2) = 0.44), respectively. Their relative growth, expressed as the bifurcation-to-prebifurcation length ratio, was stable from the age of 16 weeks and attained the value 0.22 +/- 0.05. The proximal external transverse diameter of the trachea was greater (36 fetuses, 49.3%), smaller (34 fetuses, 46.6%) or similar (3 fetuses, 4.1%), when compared to the distal external transverse diameter. The values for proximal and distal transverse diameters ranged from 2.39 +/- 0.04 to 5.20 +/- 0.17 mm and from 2.42 +/- 0.20 to 4.93 +/- 0.08 mm, expressed by the functions: y = -9.659 + 4.574 * ln (Age) +/- 0.313 (R (2) = 0.79) and y = -10.897 + 4.984 * ln (Age) +/- 0.327 (R (2) = 0.81). The values of proximal external cross-sectional area ranged from 3.38 +/- 0.12 to 15.98 +/- 1.04 mm(2), according to the linear function y = -11.798 + 1.077 * Age +/- 1.463 (R (2) = 0.78). The values of external volume of the trachea ranged from 34.3 +/- 11.6 to 370.6 +/- 94.1 mm(3) and generated the quadratic function y = -154.589 + 0.858 * Age(2) +/- 34.196 (R (2) = 0.87). CONCLUSIONS: The tracheal parameters do not show male-female differences. The developmental dynamics of prebifurcation and bifurcation lengths and proximal and distal external transverse diameters of the trachea follow linear functions dependent on the natural logarithm of fetal age, its external cross-sectional area-according to a linear function, and its external volume-according to a quadratic function. PMID- 21984198 TI - Sublytic C5b-9 complexes induce proliferative changes of glomerular mesangial cells in rat Thy-1 nephritis through TRAF6-mediated PI3K-dependent Akt1 activation. AB - The proliferation of glomerular mesangial cells (GMCs) and secretion of extracellular matrix (ECM) in rat Thy-1 nephritis (Thy-1N), resembling human mesangioproliferative glomerulonephritis (MsPGN), have been studied for many years, but the mechanisms, especially the role of signalling pathway activation and its regulation in GMCs triggered by sublytic C5b-9 complexes in Thy-1N rats remain largely unclear. In the study, the proliferation of GMCs and production of ECM as well as the role of PI3K/Akt and its regulation, both in GMCs induced by sublytic C5b-9 (in vitro) and in the renal tissues of rats with Thy-1N (in vivo), were determined and the results revealed that GMCs proliferation and ECM secretion, both in vitro and in vivo, were notably increased, and that PI3K/Akt1 activation and its regulation, such as TNF receptor-associated factor 6 (TRAF6) mediated Akt1 ubiquitination and PI3K-dependent Akt1 phosphorylation, were involved in the process of Thy-1N induction. On the other hand, silence of the TRAF6, PI3K or Akt1 genes could obviously diminish the proliferative damages and urinary protein secretion of Thy-1N rats. Together, these data implicated that sublytic C5b-9 complexes in Thy-1N rats could promote GMCs proliferation and ECM production through TRAF6-mediated PI3K-dependent Akt1 activation, in which the ubiquitination and phosphorylation of the Akt1 signal molecule played an important role in the initiation and development of the proliferative changes in the rats with Thy-1N. PMID- 21984197 TI - Interplay between insulin resistance and estrogen deficiency as co- activators in carcinogenesis. AB - Both insulin resistance and estrogen deficiency result in complex metabolic disorder based mainly on defective cellular glucose uptake and on an atherogenic serum lipid profile. These alterations may be regarded as high risks for several life-threatening human diseases, such as type-2 diabetes, cardiovascular lesions and malignancies. Insulin resistance and estrogen deficiency are concomitant disorders with mutual interrelationship. Insulin resistance and the compensatory hyperinsulinemia provoke increased androgen synthesis at the expense of decreased estrogen production. Similarly, a moderate or severe decrease in serum estrogen levels enhances the prevalence of insulin resistant states both in men and women. Healthy premenopausal women enjoy the defensive effect of estrogens against metabolic and hormonal disorders. However, even a slight decrease in their circulatory estrogen levels associated with insulin resistance may increase the risk for cancers, particularly in the organs having high estrogen demand (breast, endometrium and ovary). On the other hand, postmenopausal state with profound estrogen deficiency confers high risk for cancers in different organs with either high or moderate estrogen demand. After menopause, hormone replacement therapy improves insulin sensitivity and decreases the enhanced inclination to malignancies in postmenopausal women. Recognition of the thorough interplay between insulin resistance and estrogen deficiency may illuminate many apparently controversial experimental and clinical findings concerning cancer development and therapeutic possibilities. Moreover, their interactions in the initiation and progression of human malignancies may supply new strategies in primary cancer prevention and cancer cure. PMID- 21984199 TI - Protection against protein aggregation by alpha-crystallin as a mechanism of preconditioning. AB - Anesthetic preconditioning occurs when cells previously exposed to inhaled anesthetics are protected against subsequent injury. We hypothesize that inhaled anesthetics may cause slight protein misfolding that involves site-specific dehydration, stimulating cytoprotective mechanisms. Human neuroblastoma cells were exposed to ethanol (as the dehydration agent) followed by quantitative analysis of the expression of five heat shock genes: DNAJC5G, CRYAA, HSPB2, HSF4 and HSF2. There was an ethanol-induced upregulation of all genes except HSF4, similar to previous observations using isoflurane. CRYAA (the gene for alphaA crystallin) exhibited a 23.19 and 17.15-fold increase at 24 and 48 h post ethanol exposure, respectively. Additionally, we exposed glyceraldehyde 3-phosphate dehydrogenase to ethanol, which altered oligomeric subspecies and caused protein aggregation in a concentration-dependent manner. Ethanol-mediated dehydration induced protein aggregation was prevented by incubation with alpha-crystallin. These data indicate that ethanol mimics the effects of isoflurane presumably through a cellular preconditioning mechanism that involves dehydration-induced protein aggregation. PMID- 21984200 TI - Influence of intraventricular application of baclofen on arterial blood pressure and neurotransmitter concentrations in the hypothalamic paraventricular nucleus of rats. AB - The hypothalamic paraventricular nucleus (PVN) is a key site for regulating neuroendocrine functions in the magnocellular part and autonomic activities in the parvocellular part. Its anatomical proximity to the third ventricle could be a good target for intrathecal injection of baclofen. We investigated the correlation of intrathecal application of baclofen (a specific GABAB receptor agonist) and the release of epinephrine, norepinephrine, dopac, homovanillinic acid (HVA), glutamate and aspartate from the PVN. The decomposition products HVA, dopa and dopac of norepinephrine, epinephrine and dopamine, respectively, were used as parameters for the secretion of dopamine. We implanted a microdialysis probe in the PVN of 25 Wistar rats. In 13 rats, 1.5 MUg baclofen was injected in the lateral ventricle and the equivalent quantity of Ringer's lactate solution injected in the remaining 12 rats as a control group. Neurotransmitters and amino acids were quantified by high-performance liquid chromatography. There was a conspicuous but not significant effect of baclofen concerning the secretion of epinephrine, norepinephrine, dopac, glutamate and aspartate from the PVN. A significant increase in HVA concentration was observed only in rats treated with baclofen compared with the control group. These findings suggest that baclofen influences the secretion of neurotransmitters and amino acids involved in autonomic activities mediated by GABAB receptors. PMID- 21984201 TI - Relationship between Sonic hedgehog protein, brain-derived neurotrophic factor and oxidative stress in autism spectrum disorders. AB - The etiology of autism spectrum disorders (ASD) is not well known but oxidative stress has been suggested to play a pathological role. We report here that the serum levels of Sonic hedgehog (SHH) protein and brain-derived neurotrophic factor (BDNF) might be linked to oxidative stress in ASD. By using the whole blood or polymorphonuclear leukocytes, we demonstrated that autistic children produced a significantly higher level of oxygen free radicals (OFR). In addition, we found significantly higher levels of serum SHH protein in children with mild as well as severe form of autism. We also found that the serum level of BDNF was significantly reduced in autistic children with mild form of the disorder but not with severe form of the disorder. Our findings are the first to report a correlation between SHH, BDNF and OFR in autistic children, suggesting a pathological role of oxidative stress and SHH in autism spectrum disorders. PMID- 21984202 TI - Neutral and ion chemistry in low pressure dc plasmas of H2/N2 mixtures: routes for the efficient production of NH3 and NH4(+). AB - The chemistry in low pressure (0.8-8 Pa) plasmas of H(2) + 10% N(2) mixtures has been experimentally investigated in a hollow cathode dc reactor using electrical probes for the estimation of electron temperatures and densities, and mass spectrometry to determine the concentration of ions and stable neutral species. The analysis of the measurements by means of a kinetic model has allowed the identification of the main physicochemical mechanisms responsible for the observed distributions of neutrals and ions and for their evolution with discharge pressure. The chemistry of neutral species is dominated by the formation of appreciable amounts of NH(3) at the metallic walls of the reactor through the successive hydrogenation of atomic nitrogen and nitrogen containing radicals. Both Eley-Rideal and Langmuir-Hinshelwood mechanisms are needed in the chain of hydrogenation steps in order to account satisfactorily for the observed ammonia concentrations, which, in the steady state, are found to reach values ~30 70% of those of N(2). The ionic composition of the plasma, which is entirely due to gas-phase processes, is the result of a competition between direct electron impact dissociation, more relevant for high electron temperatures (lower pressures), and ion-molecule chemistry that prevails for the lower electron temperatures (higher pressures). At the lowest pressure, products from the protonation of the precursor molecules (H(3)(+), N(2)H(+) and NH(4)(+)) and others from direct ionization (H(2)(+) and NH(3)(+)) are found in comparable amounts. At the higher pressures, the ionic distribution is largely dominated by ammonium. It is found that collisions of H(3)(+), NH(3)(+) and N(2)H(+) with the minor neutral component NH(3) are to a great extent responsible for the final prevalence of NH(4)(+). PMID- 21984203 TI - Surgical treatment of acute fingernail injuries. AB - The fingernail has an important role in hand function, facilitating the pinch and increasing the sensitivity of the fingertip. Therefore, immediate and proper strategy in treating fingernail injuries is essential to avoid aesthetic and functional impairment. Nail-bed and fingertip injuries are considered in this review, including subungual hematoma, wounds, simple lacerations of the nail bed and/or matrix, stellate lacerations, avulsion of the nail bed, ungual matrix defect, nail-bed injuries associated with fractures of the distal phalanx, and associated fingertip injuries. All these injuries require careful initial evaluation and adequate treatment, which is often performed under magnification. Delayed and secondary procedures of fingernail sequelae are possible, but final results are often unpredictable. PMID- 21984204 TI - Appendectomy and cancer risk in Jewish BRCA1 and BRCA2 mutation carriers. AB - Previous studies suggested that appendectomy may affect cancer risk in the general population. No data on the effect of appendectomy on cancer risk in BRCA1 and BRCA2 carriers is available. Data on appendectomy, cancer type, and age at diagnosis were collected from BRCA1 (n = 677) and BRCA2 (n = 270) female Jewish Israeli mutation carriers counseled in a single medical center. Data were also collected on 225 consecutive ovarian cancer cases treated at the same medical center. Overall, 367/947 (38.7%) of mutation carriers had breast cancer (age at diagnosis 44.1 +/- 10.4 years), 142 (15.0%) ovarian cancer (53.6 +/- 10.1 years), and 438 (46.25%) were asymptomatic carriers (age at counseling 41.4 +/- 11.2 years). Mean age at diagnosis of consecutive ovarian cancer cases was 53.6 +/- 10.1 years. Of mutation carriers, 28/367 breast cancer cases (7.6%), 15/142 ovarian cancer cases (10.6%), and 11/438 asymptomatic carriers (2.5%) underwent prior appendectomy (P = 0.001 for breast/ovarian cancer when compared with asymptomatic carriers). In all but two cases, appendectomy was performed more than 10 years before cancer diagnosis or age at counseling. Of ovarian cancer patients, 12/225 (5.3%) underwent appendectomy, and in 10 appendectomy was performed 10 years or more before ovarian cancer diagnosis (P = 0.068 when compared with inherited ovarian cancer cases). This study suggests that prior appendectomy is more frequently noted in BRCA1 and BRCA2 carriers with breast and ovarian cancer than in unaffected mutation carriers. The mechanism for this association is elusive, and future analyses of ethnically diverse mutation carriers are needed to validate these results. PMID- 21984205 TI - Open vs robot-assisted laparoscopic gastric resection with D2 lymph node dissection for adenocarcinoma: a case-control study. AB - BACKGROUND: A population-based case-control study was conducted in order to investigate the advantages of robot-assisted gastric resection (RGR) for gastric cancer as opposed to traditional open gastrectomy (OG). METHODS: Data were collected in two prospectively maintained databases on patients who underwent a D2 gastrectomy with curative intent for primary gastric adenocarcinoma. All (n = 29) the first consecutive gastric cancer patients submitted to RGR from a referral centre for minimally invasive surgery were matched to control cancers (n = 120) extrapolated from a high volume centre database including patients submitted to OG. RESULTS: Robot-assisted laparoscopic procedures implied increased operative time (290 vs 222 min, p = 0.004), decreased blood loss (197.6 vs 386.1 mL, p = 0.0001) and shorter hospital stay (9.6 vs 13.4 days, p < 0.0009). There was no difference in the mean number of harvested lymph nodes between the two groups (28.0 vs 31.7, p = 0.023). The total morbidity rate, including major complications such as anastomotic and duodenal suture failure, was comparable between groups (41.4% vs 42.5%; in the RGR and OG, respectively, p = 0.764). Preliminary data on overall survival did not show prognostic differences between the two groups (p = 0.615). CONCLUSIONS: Robot-assisted surgery fulfils oncologic criteria for D2 dissection and has an oncologic outcome comparable with that of OG. RGR resulted in shorter hospital stays, the loss of less blood and morbidity comparable with that of OG. Randomized clinical trials and longer follow-up are needed to evaluate whether RGR achieves long-term survival rates equivalent to that of open and laparoscopic surgery. PMID- 21984206 TI - Core/Sheath organic nanocable constructed with a master-slave molecular pair for optically switched memories. PMID- 21984207 TI - Severe toxicity due to injected but not oral or nasal abuse of methylphenidate tablets. AB - BACKGROUND: Non-medical use of methylphenidate is increasing. Little is known about potential acute medical complications associated with recreational use of methylphenidate. STUDY AIM: To identify medical problems associated with methylphenidate abuse. METHODS: Retrospective case series of methylphenidate abuse cases presenting to an inner city emergency department. RESULTS: We identified 14 cases of methylphenidate abuse between 2003 and 2010. Ten of these patients abused methylphenidate alone while four co-ingested other drugs, mainly alcohol. The route of ingestion was oral in nine patients, nasal in one and intravascular in four. Severe toxicity was exclusively observed in users who injected the drug. Two cases involved accidental intra-arterial injection and resulted in tissue necrosis leading to the amputation of a forearm and of fingertips, respectively. Clinical findings in the non-serious cases included mild to moderate symptoms and signs of sympathetic nervous stimulation such as agitation, tachycardia, hypertension, anxiety, hallucination, headache, tremor and dizziness. Nine of the fourteen patients were taking methylphenidate as a prescribed drug. Eight patients were former or current multiple substance abusers. CONCLUSION: Methylphenidate misuse is not a significant burden for emergency departments in Switzerland. Oral and nasal administration of methylphenidate did not result in severe toxicity. However, injection of crushed methylphenidate pills lead to serious local toxicity. Most patients with methylphenidate abuse had a prescription for the drug indicating deviation from medical use. A history of multiple substance use may be a risk factor for non medical use of methylphenidate. PMID- 21984208 TI - Crystal structures of aprataxin ortholog Hnt3 reveal the mechanism for reversal of 5'-adenylated DNA. AB - Aprataxin is a DNA deadenylase that resolves DNA 5'-AMP termini and reverses abortive DNA ligation. The crystal structures of Schizosaccharomyces pombe aprataxin Hnt3 in its apo form and in complex to dsDNA and dsDNA-AMP reveal how Hnt3 recognizes and processes 5'-adenylated DNA in a structure-specific manner. The bound DNA adopts a 5'-flap conformation that facilitates 5'-AMP access to the active site, where AMP cleavage occurs by a canonical catalytic mechanism. PMID- 21984209 TI - Crystal structures of the extracellular domain of LRP6 and its complex with DKK1. AB - Low-density-lipoprotein (LDL) receptor-related proteins 5 and 6 (LRP5/6) are Wnt co-receptors essential for Wnt/beta-catenin signaling. Dickkopf 1 (DKK1) inhibits Wnt signaling by interacting with the extracellular domains of LRP5/6 and is a drug target for multiple diseases. Here we present the crystal structures of a human LRP6-E3E4-DKK1 complex and the first and second halves of human LRP6's four propeller-epidermal growth factor (EGF) pairs (LRP6-E1E2 and LRP6-E3E4). Combined with EM analysis, these data demonstrate that LRP6-E1E2 and LRP6-E3E4 form two rigid structural blocks, with a short intervening hinge that restrains their relative orientation. The C-terminal domain of DKK1 (DKK1c) interacts with the top surface of the LRP6-E3 YWTD propeller and given their structural similarity, probably also that of the LRP6-E1 propeller, through conserved hydrophobic patches buttressed by a network of salt bridges and hydrogen bonds. Our work provides key insights for understanding LRP5/6 structure and the interaction of LRP5/6 with DKK, as well as for drug discovery. PMID- 21984210 TI - Structure of an aprataxin-DNA complex with insights into AOA1 neurodegenerative disease. AB - DNA ligases finalize DNA replication and repair through DNA nick-sealing reactions that can abort to generate cytotoxic 5'-adenylation DNA damage. Aprataxin (Aptx) catalyzes direct reversal of 5'-adenylate adducts to protect genome integrity. Here the structure of a Schizosaccharomyces pombe Aptx-DNA-AMP Zn(2+) complex reveals active site and DNA interaction clefts formed by fusing a histidine triad (HIT) nucleotide hydrolase with a DNA minor groove-binding C(2)HE zinc finger (Znf). An Aptx helical 'wedge' interrogates the base stack for sensing DNA ends or DNA nicks. The HIT-Znf, the wedge and an '[F/Y]PK' pivot motif cooperate to distort terminal DNA base-pairing and direct 5'-adenylate into the active site pocket. Structural and mutational data support a wedge-pivot-cut HIT-Znf catalytic mechanism for 5'-adenylate adduct recognition and removal and suggest that mutations affecting protein folding, the active site pocket and the pivot motif underlie Aptx dysfunction in the neurodegenerative disorder ataxia with oculomotor apraxia 1 (AOA1). PMID- 21984211 TI - Structure and nucleosome interaction of the yeast NuA4 and Piccolo-NuA4 histone acetyltransferase complexes. AB - We have used EM and biochemistry to characterize the structure of NuA4, an essential yeast histone acetyltransferase (HAT) complex conserved throughout eukaryotes, and we have determined the interaction of NuA4 with the nucleosome core particle (NCP). The ATM-related Tra1 subunit, which is shared with the SAGA coactivator complex, forms a large domain joined to a second region that accommodates the catalytic subcomplex Piccolo and other NuA4 subunits. EM analysis of a NuA4-NCP complex shows the NCP bound at the periphery of NuA4. EM characterization of Piccolo and Piccolo-NCP provided further information about subunit organization and confirmed that histone acetylation requires minimal contact with the NCP. A small conserved region at the N terminus of Piccolo subunit enhancer of Polycomb-like 1 (Epl1) is essential for NCP interaction, whereas the subunit yeast homolog of mammalian Ing1 2 (Yng2) apparently positions Piccolo for efficient acetylation of histone H4 or histone H2A tails. Taken together, these results provide an understanding of the NuA4 subunit organization and the NuA4-NCP interactions. PMID- 21984212 TI - Body packers: a plea for conservative treatment. AB - BACKGROUND: The incidence of smuggling and transporting of illegal drugs by internal concealment, also known as body packing, is increasing in the Western world. The objective of this study was to determine the outcome of conservative and surgical approaches in body packers. MATERIALS AND METHODS: Clinical data on body packers admitted to our hospital from January 2004 until December 2009 were collected. The protocol for body packers required surgery when packets were present in the stomach for >48 h. Outcomes of the conservative and surgical group were assessed and analyzed. Morbidity and mortality were assessed in body packers with drug packets present in the stomach for <48 h and in those with gastric packets for >48 h. RESULTS: During the study period, more body packers were treated conservatively. Mortality was 2% in all patients and was due to intoxication. There were no significant differences of mortality, hospital admission time, and ICU admission time in the compared groups with drug packets in the stomach for less or >48 h. In 24% (4/17) of the patients with bad package material, a ruptured drug packet was found during surgery. This resulted in death in only one patient. CONCLUSION: Drug packets in the stomach for >48 h are not an indication for surgery. We recommend that surgery should only be performed in body packers with signs of intoxication or ileus and reserve conservative treatment for all other patients. PMID- 21984213 TI - Heart rate variability in children with Fontan circulation: lateral tunnel and extracardiac conduit. AB - The technique in Fontan surgery has developed from the lateral tunnel (LT) toward the extracardiac conduit (EC) used to reduce long-term complications such as atrial arrhythmia and sinus node dysfunction. Heart rate variability (HRV) examines cardiac nervous activity controlling the sinus node. This study aimed to investigate HRV in a cohort of children with univentricular hearts, focusing on the relation between HRV and surgical procedure. For 112 children with Fontan circulation, HRV was analyzed using power spectral analysis. Spectral power was determined in three regions: very-low-frequency (VLF), low-frequency (LF), and high-frequency (HF) regions. Patients were compared with 66 healthy controls subject. Patients with LT were compared with patients who had EC. The children with Fontan circulation showed a significantly reduced HRV including total power (P < 0.0001), VLF (P < 0.0001), LF (P < 0.0001), and HF (P = 0.001) compared with the control subjects. The LT and EC patients did not differ significantly. Reduced HRV was found in both the LT and EC patients. In terms of HRV reduction, EC was not superior to LT. PMID- 21984215 TI - Abstracts of the Irish Thoracic Society Scientific Meeting. November 11-1, 2011. Stillorgan, County Dublin, Ireland. PMID- 21984214 TI - Emotional and behavioral adjustment in typically developing siblings of children with autism spectrum disorders. AB - Research findings describing the emotional and behavioral functioning of typically developing (TD) siblings of children with autism spectrum disorders (ASD) are contradictory. Methodological issues, such as small study sample sizes and reliance on parent report, may contribute to inconsistent findings. The purpose of this study was to use parent and teacher report to describe presence of internalizing and externalizing behaviors among a large sample (n = 486) of TD siblings of children with ASD. Results indicated that siblings did not exhibit a disproportionate prevalence of internalizing or externalizing symptoms in comparison to the standardization sample of the rating scale. The presence of a sibling with an ASD may not be considered a risk-factor for adjustment problems among TD siblings. PMID- 21984216 TI - Costo-iliac distance: a physical sign of understated importance. AB - INTRODUCTION: Osteoporosis is a common condition, especially affecting the older female population. The ability to predict loss of lumbar height using simple anatomical measurements would be a useful tool. METHODS: Forty subjects were recruited. Mean age was 72 years. Arm span (AS) and the costo-iliac distance (CID) were measured. The CID/AS ratio was calculated. The L(1)-L(4) vertebral height of each patient was obtained from dual-energy X-ray absorptiometry (DEXA). RESULTS: There was a statistically significant correlation between the lumbar height and CID/AS ratio (R (2) = 0.79, p < 0.001). CONCLUSION: The CID/AS ratio may be a useful bedside test in identifying loss of lumbar vertebral height. PMID- 21984217 TI - Complete genome sequences and phylogenetic analysis of hepatitis delta viruses isolated from nine Turkish patients. AB - Hepatitis delta virus (HDV) is a subviral agent of hepatitis B virus (HBV), and its life cycle is dependent on HBV. It is commonly accepted that HDV has eight distinct genotypes. In this study, the complete nucleotide sequences of HDV genomes isolated from nine Turkish patients were obtained by RT-PCR using two pairs of primers that cover the entire HDV genome. PCR products were sequenced directly. The results showed that these 9 isolates were approximately 1680 base pairs in length and clustered in the genotype HDV-1 branch when phylogenetic analysis was done with the sequences together with the complete sequences of HDV genomes representing each genotype retrieved from GenBank. Analysis of a portion of the large hepatitis D antigen (L-HDAg) gene showed that sequence similarity among these Turkish isolates is between 87.4 and 97.1%, and the Turkish isolates have the most sequence similarity to HDV-1 (90.5%), while they have the least sequence similarity to HDV-3 (64.1%). Full-genome analysis indicates that the sequence similarity is between 80.7 and 95.4%, and the highest sequence similarity is 84.8% (between the Turkish isolates and HDV-1). The lowest sequence similarity is 56.4% (between the Turkish isolates and HDV-3). In conclusion, phylogenetic analysis shows that the Turkish HDV isolates belong to HDV-1. PMID- 21984218 TI - Comparative full-length sequence analysis of Marek's disease virus vaccine strain 814. AB - The complete DNA sequence of Marek's disease virus (MDV) serotype 1 vaccine strain 814 was determined. It consisted of 172,541 bp, with an overall gene organization identical to that of the MDV-1 type strains. Comparative genomic analysis of vaccine strains (814 and CVI988) and other strains (CU-2, Md5, and Md11) showed that 814 was most similar to CVI988. Several unique insertions, deletions, and substitutions were identified in strain 814. Of note, a 177-bp insertion in the overlapping genes encoding the Meq, RLORF6, and 23-kDa proteins of strain 814 was identified, and a 69-bp deletion was also located in the origin of replication site (Ori) in the gene encoding RLORF12. Compared to the CVI988 vaccine strain, a deletion of 510 bp was identified in the UL36 gene. These analyses identified key mutations in the 814 strain and the vaccine strain that could be exploited for future MDV vaccine design. PMID- 21984219 TI - Copper toxicity and the origin of bacterial resistance--new insights and applications. AB - The bioavailability of different metals has likely changed over the course of Earth's history. Based on geochemical models, copper became much more bioavailable with the advent of an oxidizing atmosphere. This posed both a challenge and an opportunity for the organisms at that time. Specifically, copper resistance mechanisms were required first and to do this Bacteria appear to have modified already existing protein structures. Later, Cu-utilizing proteins evolved and continue to be used sparingly, at least relative to later evolving Eukarya, by Bacteria but with significant biogeochemical consequences. Copper is a strong soft metal that can attack intracellular iron-sulfur centers of various proteins under primarily anoxic conditions. In oxic conditions, copper can catalyze a Fenton-like reaction that may cause lipid peroxidation and protein damage. The inherent ability of copper to inflict damage upon multiple cellular functions has been harnessed by macrophages and perhaps amoeba to kill and later digest bacteria and other microorganisms. Notably, these organisms, unlike Bacteria, most likely evolved after increases in copper availability, implying that Eukarya utilized their own trafficking and resistance mechanisms, in addition to the natural toxicity of copper, as leverage in interactions with Bacteria. In an "arms race," some pathogenic bacteria have evolved new mechanisms for copper resistance, which is relevant given renewed interest in the use of copper surfaces due to their antimicrobial properties. PMID- 21984220 TI - In vitro evaluation of clinical activity and toxicity of anticancer drugs using tumor cells from patients and cells representing normal tissues. AB - PURPOSE: The aim of this study was to evaluate a phenotypic cell panel with tumor cells from various patients and normal cells for preclinical profiles of antitumor efficacy and toxicity of anticancer drugs. METHODS: The antitumor activity of fourteen anticancer drugs was tested in over one hundred tumor samples from patients with solid or hematological malignancies. Drug activity against four normal cell types was used for the assessment of normal tissue toxicity. In vitro activity of the drugs was compared with indications approved by the Food and Drug Administration and established adverse event profiles. RESULTS: In general, in vitro drug activity in tumor cells from patients reflected known clinical activity of the drugs investigated. For example, the clinical activity of imatinib in chronic myeloid leukemia was clearly detected in the tumor panel. Further, and in accordance with clinical use, cisplatin and bortezomib showed high activity in ovarian cancer and myeloma samples, respectively. The normal cell models roughly reflected known clinical toxicity profiles and were able to detect differences in therapeutic index, e.g., between targeted drugs and classical cytotoxic agents. For example, the high tolerability of imatinib and the well-known renal toxicity of cisplatin were demonstrated. CONCLUSIONS: In preclinical drug development, primary tumor cells from patients can be used for the prediction of cancer diagnosis-specific activity and may aid in the selection of diagnoses for clinical trials. By using tumor and toxicity panels together, information about therapeutic index may be derived, which may be useful when choosing among drug candidates with similar tumor effects. PMID- 21984221 TI - The role of MTHFR and RFC1 polymorphisms on toxicity and outcome of adult patients with hematological malignancies treated with high-dose methotrexate followed by leucovorin rescue. AB - PURPOSE: In the last years, the influence of different genes involved in metabolism of chemotherapeutic agents has been studied. Methotrexate (MTX) is a key compound of chemotherapeutic regimens used in the treatment of acute lymphoblastic leukemia (ALL), primary central nervous system lymphoma (PCNSL) and Burkitt's lymphomas (BL). This study aims to evaluate the role of MTHFR C677T and A1298C polymorphisms and G80A reduced folate carrier gene (RFC1) in a cohort of adult patients with lymphoproliferative malignancies submitted to high-dose MTX followed by leucovorin rescue. METHODS: We performed the analysis of these polymorphisms on genomic DNA with RFLP-PCR. RESULTS: Patients carrying MTHFR A1298C variant showed decreased hepatic and hematological toxicity (P = 0.03). Overall survival (OS) and progression-free survival (PFS) between homozygous wild type and variant patients for the RFC1 G(80)A were significantly different (P = 0.035 and P = 0.02, respectively). A significant correlation between hematological toxicity and age (P = 0.003) was observed. There was no significant influence of MTHFR C677T genotype on toxicity, OS and PFS. CONCLUSIONS: Leucovorin rescue given after high-dose MTX probably accounts for the lack of influence of C677T polymorphism. To better define a role of RFC1 polymorphism on patients outcome, it would be worthwhile to perform a study on intracellular MTX level and RFC1 substrate binding affinities in different genotypes. PMID- 21984222 TI - Pharmacokinetic drug interaction between AEE788 and RAD001 causing thrombocytopenia in patients with glioblastoma. AB - PURPOSE: Treating glioblastoma through the simultaneous inhibition of multiple transduction pathways may prove more effective than single-pathway inhibition. We evaluated the safety, biologic activity, and pharmacokinetic profile of oral AEE788, a selective inhibitor of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), plus oral RAD001, a mammalian target of rapamycin inhibitor, in glioblastoma patients. METHODS: This phase IB/II, open label, multicenter, 2-arm, dose-escalation study enrolled adult glioblastoma patients at first or second recurrence/relapse. Primary objective was to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of AEE788 combined with RAD001. Secondary objectives included determining the safety/tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of the combination. RESULTS: Sixteen patients were enrolled (AEE788 200 mg/day + RAD001 5 mg/day, 2 patients; AEE788 150 mg/day + RAD001 5 mg every other day [qod], 14); all patients discontinued the study most commonly because of disease progression. Four patients experienced DLT (AEE788 200 mg/day + RAD001 5 mg/day, 1 patient; AEE788 150 mg/day + RAD001 5 mg qod, 3). Both patients receiving AEE788 (200 mg/day) plus RAD001 (5 mg/day) experienced clinically significant thrombocytopenia requiring a dose reduction/interruption. AEE788 appeared to inhibit the metabolism of RAD001. The study was terminated prematurely before an MTD was determined because of safety findings in other studies evaluating AEE788 monotherapy. CONCLUSIONS: The coadministration of AEE788 and RAD001 in glioblastoma patients caused a clinically significant thrombocytopenia and a higher-than-expected RAD001 area under the curve concentration when dosed at 200 and 5 mg/day, respectively. After a dose reduction to AEE788 (150 mg/day) and RAD001 (5 mg qod), the combination appeared to be better tolerated. PMID- 21984223 TI - Cost-effectiveness of open versus laparoscopic appendectomy: a multilevel approach with propensity score matching. AB - OBJECTIVE: To compare postoperative complications and cost of treatment of laparoscopic (LA) versus open appendectomy (OA) and to identify the most cost effective treatment method. METHODS: Patients treated for appendectomy in US veterans health administration (VHA) hospitals in 2005 were included into our study. Direct medical cost and postoperative complications during hospitalization were used as outcomes. Propensity score matching was employed to adjust for baseline imbalances between treatment groups. It was adjusted for the severity of appendicitis, comorbidities according to Charlson Comorbidity Index, and demographic variables. 1:1 optimal matching with replacement was performed. Based on the matched samples, we estimated generalized linear mixed regression models for costs (gamma model) and postoperative complications (logit model). Besides patients' covariates, predictors of hospital resource use and quality of care at the hospital level were considered as explanatory variables. RESULTS: The total study population comprised of 1,128 patients (370 LA, 758 OA) from 95 VHA hospitals. Type of appendectomy had a significant influence on total costs (P=0.005), with predicted costs for LA being 17.1% lower in comparison to OA (OA: 10,851 US$ [95%CI: 9,707 US$; 12,131 US$] vs. LA: 8,995 US$ [95%CI: 8,073 US$; 10,022 US$]). Differences in the predicted overall postoperative complication were not significant between LA and OA (P=0.6311). Severity of appendicitis had a significant impact on costs and postoperative complications. CONCLUSION: Predicted costs for LA were 1,856 US$ lower than for OA while the postoperative complication rate did not differ significantly. Thus, LA is the treatment of choice from a provider's perspective. PMID- 21984224 TI - The welfare implications of disability for older people in Ireland. AB - Recent data analysed for Ireland suggest a strong link between disability status and household poverty, while there exists substantial evidence to suggest that disability is highly prevalent among persons of older age. Within this context, this paper estimates the welfare implications of disability for older people in Ireland. We define and estimate models of the private costs borne by households with older persons who have a disability in Ireland, both in general and by severity of illness or condition. Our modelling framework is based on the standard of living approach to estimating the cost of disability. The model quantifies the extra costs of living associated with disability and is estimated by comparing the standard of living of households with and without disabled members at a given income, controlling for other sources of variation. The analysis suggests that the estimated economic cost of disability for older people in Ireland is significant and varies by severity of disability, as well as by household type. The results also suggest that the cost of disability increases in proportionate terms as the number of people in the household decreases. Our results are important when considering the effectiveness of policies that aim to address the economic problems associated with disability for older people, suggesting that current policy in Ireland does not go far enough. They indicate that older people face a double jeopardy through age and disability, which is not reflected in official poverty rates and support the case for the introduction of disability-adjusted poverty payments. PMID- 21984225 TI - Individual and institutional influences on faith-based health and wellness programming. AB - The majority of the US population is affiliated with faith-based organizations (FBO). Health and wellness activities (HWAs) within FBOs have great potential for reach, though the factors influencing faith-based HWA are not well understood. The purpose of this study was to examine individual faith leader and institutional influences on HWAs offered within FBOs. A national convenience sample of faith leaders (N = 844) completed an online survey assessing individual (demographics, health, health behaviors and attitudes) and institutional influences (size, location and external support) on health and HWA within FBO. Respondents were primarily White (93%), male (72%), middle-aged and affiliated with Methodist (42.5%) or Lutheran (20.2%) religions. Respondents reported 4.8 +/ 3.2 HWA within their FBO per year. Faith leader education, length of service to the FBO, physical activity and fruit/vegetable intake were positively related to HWA and body mass index was negatively related. Denomination, congregation diversity, location and size were also related to HWA. Results show a strong relationship between faith leaders' health and HWA, indicating the influence of the social environment on health promotion in FBOs. Institutional variables, though not modifiable, were significant predictors of HWA and should be considered when delivering interventions to achieve a significant impact. PMID- 21984226 TI - Evaluation of doripenem utilization and susceptibilities at a large urban hospital. AB - BACKGROUND: Bacterial resistance presents a constant challenge in the treatment of hospitalized patients, particularly with Gram-negative infections. Carbapenems have an important role in the treatment of resistant nosocomial organisms. Doripenem, a recently approved carbapenem, has shown efficacy in clinical trials, but there is little published data on utilization in a general patient population. OBJECTIVE: The clinical utilization of doripenem in a general adult inpatient population was evaluated during a carbapenem formulary conversion. SETTING: A 706-bed acute care tertiary hospital serving an urban community. METHODS: After formulary conversion to doripenem, the first 100 patients to receive doripenem were included in the analysis. Baseline characteristics were recorded for each patient, along with indication for treatment, prescribing physician, dose and frequency of doripenem and duration of treatment. Patients were monitored for adverse reactions to doripenem. Bacterial culture results were recorded. For positive cultures, doripenem susceptibility was determined by Etest. Patients were followed until discontinuation of antibiotic therapy, discharge or death to determine treatment outcomes. Successful treatment was defined as clinical or microbiological cure, while patients with infection related mortality or requiring subsequent antibiotics for the index infection were considered treatment failure. MAIN OUTCOME MEASURES: Clinical utilization of doripenem, including indications and doses used. RESULTS: Doripenem treatment was recorded in 102 patients. The most common indications for treatment were pneumonia and sepsis. The majority of doripenem orders were written by Infectious Disease or Pulmonology Services. Forty-nine patients were treated successfully with doripenem and six patients experienced treatment failure. The remainder of patients were not evaluable by predefined outcomes criteria. Adverse events were reported in eight patients and included acute renal failure, Clostridium difficile-associated diarrhea and seizures. Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa were the most common organisms in culture results. Doripenem demonstrated in vitro activity against 81% of all organisms and susceptibility results had >90% correlation with meropenem and imipenem susceptibilities. CONCLUSION: In our limited sample size, doripenem was safe and effective against various types of infections in a general inpatient population with similar bacterial susceptibilities to other cabapenems. Doripenem was utilized for appropriate indications, but doses were frequently outside the manufacturers labeling. Adverse events were uncommon, and no serious adverse events were directly associated with doripenem treatment. PMID- 21984228 TI - The adenoma hunt in colorectal cancer screening: defining the target. AB - Colorectal adenomas are precursor lesions of colorectal cancer. Different biological and metabolic processes contribute to adenomagenesis. Subsequent progression to carcinoma occurs in only about 5% of the cases. Detection and removal of all adenomas would reduce CRC incidence and mortality, but at the cost of major over-treatment. Classical morphological characteristics fail to accurately discriminate between adenomas that will become malignant and those that will not. Understanding the biology of cancer development will help to better characterize adenomas at high risk of progression, and subsequently establish triage tests that allow to safely reserve colonoscopy only for individuals at high probability of having truly high-risk colorectal adenomas. Screening tests based on genomic changes that affect relevant biological and metabolic processes hold most promise in this respect. PMID- 21984227 TI - Slovenian pharmacy performance: a patient-centred approach to patient satisfaction survey content development. AB - OBJECTIVE: To identify content of pharmacy performance relevant to patient satisfaction. SETTING: Interviews with pharmacy users were conducted at their homes. The Delphi meeting was run at the Faculty of Pharmacy, Ljubljana, Slovenia. METHOD: A two-phase process was employed. In Phase I, interviews with 43 pharmacy users were conducted to identify patients' experiences and expectations relating to pharmacies. The content analysis of their responses resulted in a list of themes from which items were generated. In Phase II, a 10 member expert panel was employed in a two round Delphi technique to rate the importance of each item for the patient satisfaction. MAIN OUTCOME MEASURE: Themes derived from the interviews and their importance for patient satisfaction as assessed by the expert panel. RESULTS: Seventy-nine themes were generated from the survey responses which were grouped into four main categories: 'Relations', 'Counseling', 'Physical facilities and location' and 'Process'. In total, 69 items were generated. The expert panel rated 84% of generated items as very or somewhat important. CONCLUSION: The qualitative study provides insights on the content of pharmacy performance relevant to patients. Identified categories encompass a wide range of issues that contribute to patient satisfaction with pharmacy performance. PMID- 21984229 TI - Unpredicted electron injection in CdS/CdSe quantum dot sensitized ZrO2 solar cells. AB - A quantum dot sensitized solar cell based on a porous ZrO(2) film, sensitized with CdSe quantum dots using CdS as an intermediate layer is presented. We observe electron injection from photo-excited quantum dots into the ZrO(2), which is unexpected due to the much higher conduction band edge (closer to the vacuum level) of bulk ZrO(2) compared to TiO(2). PMID- 21984230 TI - Organocatalytic synthesis of 1,2,3-triazoles from unactivated ketones and arylazides. PMID- 21984231 TI - A vision guided hybrid robotic prototype system for stereotactic surgery. AB - BACKGROUND: Robot-assisted surgery (RAS) systems help surgeons performing accurate operations, but a number of drawbacks render them not yet suitable for clinical theaters and procedures. In this paper, a novel vision guided robotic system is proposed to facilitate navigation procedures. METHODS: A vision guided hybrid robotic system is designed, consisting of a passive serial arm and an active parallel frame. Navigation is accomplished in three steps: approaching, aiming and insertion. First, the target is safely approached with the passive arm. Second, the trajectory is automatically aligned using the parallel frame. And then the target is reached by manual insertion. A stereo camera is used to position fiducials, the robot and the surgical tool. It also provides working area images for professional surgeons at a remote site. RESULTS: The prototype system accomplished phantom and animal trials with satisfactory accuracy. The robot can easily be adjusted to avoid obstacles and quickly set up on an optimal 'approaching' place. The surgical tool is automatically aligned with the trajectory. The system can withdraw from the working area and restore the aiming posture freely. With the help of the working area images, some important navigation steps can be handled remotely. CONCLUSIONS: A novel vision guided robotic system is proposed and validated. It enables surgeons to fit the system to the clinical theater. System safety and feasibility are enhanced by multi-step navigation procedures and remote image monitoring. The system can be operated easily by general clinical staff. PMID- 21984232 TI - Vitamin D and mammographic breast density: a systematic review. AB - Studies suggest a protective relationship between Vitamin D and breast cancer risk. Several studies assessed the association of Vitamin D with mammographic breast density, a known and strong breast cancer risk factor. Understanding the potential role of Vitamin D in the modification of breast density might open new avenues in breast cancer prevention. This systematic review summarizes published studies that investigated the association between Vitamin D and mammographic breast density and offers suggestions for strategies to advance our scientific knowledge. PMID- 21984233 TI - Evidence of differences between the communities of arbuscular mycorrhizal fungi colonizing galls and roots of Prunus persica infected by the root-knot nematode Meloidogyne incognita. AB - Arbuscular mycorrhizal fungi (AMF) play important roles as plant protection agents, reducing or suppressing nematode colonization. However, it has never been investigated whether the galls produced in roots by nematode infection are colonized by AMF. This study tested whether galls produced by Meloidogyne incognita infection in Prunus persica roots are colonized by AMF. We also determined the changes in AMF composition and biodiversity mediated by infection with this root-knot nematode. DNA from galls and roots of plants infected by M. incognita and from roots of noninfected plants was extracted, amplified, cloned, and sequenced using AMF-specific primers. Phylogenetic analysis using the small subunit (SSU) ribosomal DNA (rDNA) data set revealed 22 different AMF sequence types (17 Glomus sequence types, 3 Paraglomus sequence types, 1 Scutellospora sequence type, and 1 Acaulospora sequence type). The highest AMF diversity was found in uninfected roots, followed by infected roots and galls. This study indicates that the galls produced in P. persica roots due to infection with M. incognita were colonized extensively by a community of AMF, belonging to the families Paraglomeraceae and Glomeraceae, that was different from the community detected in roots. Although the function of the AMF in the galls is still unknown, we hypothesize that they act as protection agents against opportunistic pathogens. PMID- 21984234 TI - In vitro fermentation of sugar beet arabino-oligosaccharides by fecal microbiota obtained from patients with ulcerative colitis to selectively stimulate the growth of Bifidobacterium spp. and Lactobacillus spp. AB - The potential prebiotic properties of arabino-oligosaccharides (AOS) derived from sugar beet pulp was studied using mixed cultures of human fecal bacteria from patients with ulcerative colitis (UC), in remission or with active disease, and in healthy controls. These results were compared to those for fructo oligosaccharides (FOS), which are known to have a prebiotic effect. Fermentation studies were carried out using a small-scale static batch system, and changes in the fecal microbial communities and metabolites were monitored after 24 h by quantitative real-time PCR and short-chain fatty acid analysis. With a few minor exceptions, AOS affected the communities similarly to what was seen for FOS. Quantitative real-time PCR revealed that Bifidobacterium spp. and Lactobacillus spp. were selectively increased after fermentation of AOS or FOS by fecal microbiota derived from UC patients. The stimulation of growth of Lactobacillus spp. and Bifidobacterium spp. was accompanied by a high production of acetate and hence a decrease of pH. The fermentation of AOS may help improve the inflammatory conditions in UC patients through stimulation of bacteria eliciting anti inflammatory responses and through production of acetate. AOS may therefore represent a new prebiotic candidate for reduction of the risk of flare-ups in UC patients. However, human trials are needed to confirm a health-promoting effect. PMID- 21984235 TI - The dent stage of maize kernels is the most conducive for fumonisin biosynthesis under field conditions. AB - The fungal pathogen Fusarium verticillioides infects maize ears and produces fumonisins, known for their adverse effects on human and animal health. Basic questions remain unanswered regarding the kernel stage(s) associated with fumonisin biosynthesis and the kernel components involved in fumonisin regulation during F. verticillioides-maize interaction under field conditions. In this 2 year field study, the time course of F. verticillioides growth and fumonisin accumulation in developing maize kernels, along with the variations in kernel pH and amylopectin content, were monitored using relevant and accurate analytical tools. In all experiments, the most significant increase in fumonisin accumulation or in fumonisin productivity (i.e., fumonisin production per unit of fungus) was shown to occur within a very short period of time, between 22/32 and 42 days after inoculation and corresponding to the dent stage. This stage was also characterized by acidification in the kernel pH and a maximum level of amylopectin content. Our data clearly support published results based on in vitro experiments suggesting that the physiological stages of the maize kernel play a major role in regulating fumonisin production. Here we have validated this result for in planta and field conditions, and we demonstrate that under such conditions the dent stage is the most conducive for fumonisin accumulation. PMID- 21984236 TI - Method enabling gene expression studies of pathogens in a complex food matrix. AB - We describe a simple method for stabilizing and extracting high-quality prokaryotic RNA from meat. Heat and salt stress of Escherichia coli and Salmonella spp. in minced meat reproducibly induced dnaK and otsB expression, respectively, as observed by quantitative reverse transcription-PCR (>5-fold relative changes). Thus, the method is applicable in studies of bacterial gene expression in a meat matrix. PMID- 21984237 TI - Characterization of the poly-beta-1,6-N-acetylglucosamine polysaccharide component of Burkholderia biofilms. AB - We demonstrated the production of poly-beta-1,6-N-acetylglucosamine (PNAG) polysaccharide in the biofilms of Burkholderia multivorans, Burkholderia vietnamiensis, Burkholderia ambifaria, Burkholderia cepacia, and Burkholderia cenocepacia using an immunoblot assay for PNAG. These results were confirmed by further studies, which showed that the PNAG hydrolase, dispersin B, eliminated immunoreactivity of extracts from the species that were tested (B. cenocepacia and B. multivorans). Dispersin B also inhibited biofilm formation and dispersed preformed biofilms of Burkholderia species. These results imply a role for PNAG in the maintenance of Burkholderia biofilm integrity. While PNAG was present in biofilms of all of the wild-type test organisms, a DeltapgaBC mutant of B. multivorans (Mu5) produced no detectable PNAG, indicating that these genes are needed for Burkholderia PNAG formation. Furthermore, restoration of PNAG production in PNAG negative E. coli TRXWMGDeltaC (DeltapgaC) by complementation with B. multivorans pgaBCD confirmed the involvement of these genes in Burkholderia PNAG production. While the confocal scanning laser microscopy of untreated wild-type B. multivorans showed thick, multilayered biofilm, Mu5 and dispersin B-treated wild-type biofilms were thin, poorly developed, and disrupted, confirming the involvement of PNAG in B. multivorans biofilm formation. Thus, PNAG appears to be an important component of Burkholderia biofilms, potentially contributing to its resistance to multiple antibiotics and persistence during chronic infections, including cystic fibrosis-associated infection. PMID- 21984238 TI - Imaging and analysis of Pseudomonas aeruginosa swarming and rhamnolipid production. AB - Many bacteria spread over surfaces by "swarming" in groups. A problem for scientists who study swarming is the acquisition of statistically significant data that distinguish two observations or detail the temporal patterns and two dimensional heterogeneities that occur. It is currently difficult to quantify differences between observed swarm phenotypes. Here, we present a method for acquisition of temporal surface motility data using time-lapse fluorescence and bioluminescence imaging. We specifically demonstrate three applications of our technique with the bacterium Pseudomonas aeruginosa. First, we quantify the temporal distribution of P. aeruginosa cells tagged with green fluorescent protein (GFP) and the surfactant rhamnolipid stained with the lipid dye Nile red. Second, we distinguish swarming of P. aeruginosa and Salmonella enterica serovar Typhimurium in a coswarming experiment. Lastly, we quantify differences in swarming and rhamnolipid production of several P. aeruginosa strains. While the best swarming strains produced the most rhamnolipid on surfaces, planktonic culture rhamnolipid production did not correlate with surface growth rhamnolipid production. PMID- 21984239 TI - Evaluation of subsampling-based normalization strategies for tagged high throughput sequencing data sets from gut microbiomes. AB - Several subsampling-based normalization strategies were applied to different high throughput sequencing data sets originating from human and murine gut environments. Their effects on the data sets' characteristics and normalization efficiencies, as measured by several beta-diversity metrics, were compared. For both data sets, subsampling to the median rather than the minimum number appeared to improve the analysis. PMID- 21984240 TI - Ruminant rhombencephalitis-associated Listeria monocytogenes alleles linked to a multilocus variable-number tandem-repeat analysis complex. AB - Listeria monocytogenes is among the most important food-borne pathogens and is well adapted to persist in the environment. To gain insight into the genetic relatedness and potential virulence of L. monocytogenes strains causing central nervous system (CNS) infections, we used multilocus variable-number tandem-repeat analysis (MLVA) to subtype 183 L. monocytogenes isolates, most from ruminant rhombencephalitis and some from human patients, food, and the environment. Allelic-profile-based comparisons grouped L. monocytogenes strains mainly into three clonal complexes and linked single-locus variants (SLVs). Clonal complex A essentially consisted of isolates from human and ruminant brain samples. All but one rhombencephalitis isolate from cattle were located in clonal complex A. In contrast, food and environmental isolates mainly clustered into clonal complex C, and none was classified as clonal complex A. Isolates of the two main clonal complexes (A and C) obtained by MLVA were analyzed by PCR for the presence of 11 virulence-associated genes (prfA, actA, inlA, inlB, inlC, inlD, inlE, inlF, inlG, inlJ, and inlC2H). Virulence gene analysis revealed significant differences in the actA, inlF, inlG, and inlJ allelic profiles between clinical isolates (complex A) and nonclinical isolates (complex C). The association of particular alleles of actA, inlF, and newly described alleles of inlJ with isolates from CNS infections (particularly rhombencephalitis) suggests that these virulence genes participate in neurovirulence of L. monocytogenes. The overall absence of inlG in clinical complex A and its presence in complex C isolates suggests that the InlG protein is more relevant for the survival of L. monocytogenes in the environment. PMID- 21984241 TI - Application of a bacteriophage lysin to disrupt biofilms formed by the animal pathogen Streptococcus suis. AB - Bacterial biofilms are crucial to the pathogenesis of many important infections and are difficult to eradicate. Streptococcus suis is an important pathogen of pigs, and here the biofilm-forming ability of 32 strains of this species was determined. Significant biofilms were completely formed by 10 of the strains after 60 h of incubation, with exopolysaccharide production in the biofilm significantly higher than that in the corresponding planktonic cultures. S. suis strain SS2-4 formed a dense biofilm, as revealed by scanning electron microscopy, and in this state exhibited increased resistance to a number of antibiotics (ampicillin, amoxicillin, ciprofloxacin, kanamycin, and rifampin) compared to that of planktonic cultures. A bacteriophage lysin, designated LySMP, was used to attack biofilms alone and in combination with antibiotics and bacteriophage. The results demonstrated that the biofilms formed by S. suis, especially strains SS2 4 and SS2-H, could be dispersed by LySMP and with >80% removal compared to a biofilm reduction by treatment with either antibiotics or bacteriophage alone of less than 20%; in addition to disruption of the biofilm structure, the S. suis cells themselves were inactivated by LySMP. The efficacy of LySMP was not dose dependent, and in combination with antibiotics, it acted synergistically to maximize dispersal of the S. suis biofilm and inactivate the released cells. These data suggest that bacteriophage lysin could form part of an effective strategy to treat S. suis infections and represents a new class of antibiofilm agents. PMID- 21984242 TI - Wastewater utilization for poly-beta-hydroxybutyrate production by the cyanobacterium Aulosira fertilissima in a recirculatory aquaculture system. AB - Intensive aquaculture releases large quantities of nutrients into aquatic bodies, which can lead to eutrophication. The objective of this study was the development of a biological recirculatory wastewater treatment system with a diazotrophic cyanobacterium, Aulosira fertilissima, and simultaneous production of valuable product in the form of poly-beta-hydroxybutyrate (PHB). To investigate this possible synergy, batch scale tests were conducted under a recirculatory aquaculture system in fiber-reinforced plastic tanks enhanced by several manageable parameters (e.g., sedimentation, inoculum size, depth, turbulence, and light intensity), an adequate combination of which showed better productivity. The dissolved-oxygen level increased in the range of 3.2 to 6.9 mg liter-1 during the culture period. Nutrients such as ammonia, nitrite, and phosphate decreased to as low as zero within 15 days of incubation, indicating the system's bioremediation capability while yielding valuable cyanobacterial biomass for PHB production. Maximum PHB accumulation in A. fertilissima was found in sedimented fish pond discharge at 20-cm culture depth with stirring and an initial inoculum size of 80 mg dry cell weight (dcw) liter-1. Under optimized conditions, the PHB yield was boosted to 92, 89, and 80 g m-2, respectively for the summer, rainy, and winter seasons. Extrapolation of the result showed that a hectare of A. fertilissima cultivation in fish pond discharge would give an annual harvest of ~17 tons dry biomass, consisting of 14 tons of PHB with material properties comparable to those of the bacterial polymer, with simultaneous treatment of 32,640 m3 water discharge. PMID- 21984243 TI - Fate of Escherichia coli O26 in corn silage experimentally contaminated at ensiling, at silo opening, or after aerobic exposure, and protective effect of various bacterial inoculants. AB - Shiga toxin-producing Escherichia coli (STEC) strains are responsible for human illness. Ruminants are recognized as a major reservoir of STEC, and animal feeds, such as silages, have been pointed out as a possible vehicle for the spread of STEC. The present study aimed to monitor the fate of pathogenic E. coli O26 strains in corn material experimentally inoculated (105 CFU/g) during ensiling, just after silo opening, and after several days of aerobic exposure. The addition of 3 bacterial inoculants, Propionibacterium sp., Lactobacillus buchneri, and Leuconostoc mesenteroides (106 CFU/g), was evaluated for their abilities to control these pathogens. The results showed that E. coli O26 could not survive in corn silage 5 days postensiling, and the 3 inoculants tested did not modify the fate of pathogen survival during ensiling. In the case of direct contamination at silo opening, E. coli O26 could be totally eradicated from corn silage previously inoculated with Leuconostoc mesenteroides. The combination of proper ensiling techniques and the utilization of selected bacterial inoculants appears to represent a good strategy to guarantee nutritional qualities of cattle feed while at the same time limiting the entry of pathogenic E. coli into the epidemiological cycle to improve the microbial safety of the food chain. PMID- 21984244 TI - Quantitative PCR enumeration of total/toxic Planktothrix rubescens and total cyanobacteria in preserved DNA isolated from lake sediments. AB - The variability of spatial distribution and the determinism of cyanobacterial blooms, as well as their impact at the lake scale, are still not understood, partly due to the lack of long-term climatic and environmental monitoring data. The paucity of these data can be alleviated by the use of proxy data from high resolution sampling of sediments. Coupling paleolimnological and molecular tools and using biomarkers such as preserved DNA are promising approaches, although they have not been performed often enough so far. In our study, a quantitative PCR (qPCR) technique was applied to enumerate total cyanobacterial and total and toxic Planktothrix communities in preserved DNA derived from sediments of three lakes located in the French Alps (Lake Geneva, Lake Bourget, and Lake Annecy), containing a wide range of cyanobacterial species. Preserved DNA from lake sediments was analyzed to assess its quality, quantity, and integrity, with further application for qPCR. We applied the qPCR assay to enumerate the total cyanobacterial community, and multiplex qPCR assays were applied to quantify total and microcystin-producing Planktothrix populations in a single reaction tube. These methods were optimized, calibrated, and applied to sediment samples, and the specificity and reproducibility of qPCR enumeration were tested. Accurate estimation of potential inhibition within sediment samples was performed to assess the sensitivity of such enumeration by qPCR. Some precautions needed for interpreting qPCR results in the context of paleolimnological approaches are discussed. We concluded that the qPCR assay can be used successfully for the analysis of lake sediments when DNA is well preserved in order to assess the presence and dominance of cyanobacterial and Planktothrix communities. PMID- 21984245 TI - Inhibition of Staphylococcus aureus by lysostaphin-expressing Lactobacillus plantarum WCFS1 in a modified genital tract secretion medium. AB - Lactobacillus species are a predominant member of the vaginal microflora and are critical in maintaining an acidic vaginal environment thought to contribute to the prevention of a number of urogenital diseases. However, during menstruation the pH of the vaginal environment increases to neutrality, a pH conducive for Staphylococcus aureus proliferation and the production of toxic shock syndrome toxin 1 (TSST-1) in susceptible women. In order to generate Lactobacillus species capable of expressing lysostaphin (an endopeptidase that cleaves the cell wall of S. aureus) in a modified genital tract secretion medium (mGTS) under neutral-pH conditions, six prominent proteins from Lactobacillus plantarum WCFS1 spent medium were identified by mass spectrometry. Sequences for promoters, signal peptides, and mature lysostaphin were used to construct plasmids that were subsequently transformed into L. plantarum WCFS1. The promoter and signal sequences of Lp_3014 (putatively identified as a transglycosylase) or the promoter sequence of Lp_0789 (putatively identified as glyceraldehyde 3-phosphate dehydrogenase) with the signal sequence of Lp_3014 exhibited lysostaphin activity on buffered medium containing heat-killed S. aureus. The cassettes were integrated into the chromosome of L. plantarum WCFS1, but only the cassette containing the promoter and signal sequence from Lp_3014 had integrated into the appropriate site. Coculture assays using buffered mGTS showed that lysostaphin expressed from L. plantarum WCFS1 reduced the growth of TSST-1-producing strains of S. aureus under neutral-pH conditions. This study provides the basis for determining whether lysostaphin-producing Lactobacillus strains could potentially be used as a means to inhibit the growth of S. aureus during menstruation. PMID- 21984246 TI - Production of a particulate hepatitis C vaccine candidate by an engineered Lactococcus lactis strain. AB - Vaccine delivery systems based on display of antigens on bioengineered bacterial polyester inclusions can stimulate cellular immune responses. The food-grade Gram positive bacterium Lactococcus lactis was engineered to produce spherical polyhydroxybutyrate (PHB) inclusions which abundantly displayed the hepatitis C virus core (HCc) antigen. In mice, the immune response induced by this antigen delivery system was compared to that induced by vaccination with HCc antigen displayed on PHB beads produced in Escherichia coli, to PHB beads without antigen produced in L. lactis or E. coli, or directly to the recombinant HCc protein. Vaccination site lesions were minimal in all mice vaccinated with HCc PHB beads or recombinant protein, all mixed in the oil-in-water adjuvant Emulsigen, while vaccination with the recombinant protein in complete Freund's adjuvant produced a marked inflammatory reaction at the vaccination site. Vaccination with the PHB beads produced in L. lactis and displaying HCc antigen produced antigen-specific cellular immune responses with significant release of gamma interferon (IFN gamma) and interleukin-17A (IL-17A) from splenocyte cultures and no significant antigen-specific serum antibody, while the PHB beads displaying HCc but produced in E. coli released IFN-gamma and IL-17A as well as the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and IL-6 and low levels of IgG2c antibody. In contrast, recombinant HCc antigen in Emulsigen produced a diverse cytokine response and a strong IgG1 antibody response. Overall it was shown that L. lactis can be used to produce immunogenic PHB beads displaying viral antigens, making the beads suitable for vaccination against viral infections. PMID- 21984247 TI - Tricholoma matsutake dominates diverse microbial communities in different forest soils. AB - Fungal and actinobacterial communities were analyzed together with soil chemistry and enzyme activities in order to profile the microbial diversity associated with the economically important mushroom Tricholoma matsutake. Samples of mycelium soil aggregation (shiro) were collected from three experimental sites where sporocarps naturally formed. PCR was used to confirm the presence and absence of matsutake in soil samples. PCR-denaturing gradient gel electrophoresis (DGGE) fingerprinting and direct sequencing were used to identify fungi and actinobacteria in the mineral and organic soil layers separately. Soil enzyme activities and hemicellulotic carbohydrates were analyzed in a productive experimental site. Soil chemistry was investigated in both organic and mineral soil layers at all three experimental sites. Matsutake dominated in the shiro but also coexisted with a high diversity of fungi and actinobacteria. Tomentollopsis sp. in the organic layer above the shiro and Piloderma sp. in the shiro correlated positively with the presence of T. matsutake in all experimental sites. A Thermomonosporaceae bacterium and Nocardia sp. correlated positively with the presence of T. matsutake, and Streptomyces sp. was a common cohabitant in the shiro, although these operational taxonomic units (OTUs) did not occur at all sites. Significantly higher enzyme activity levels were detected in shiro soil. These enzymes are involved in the mobilization of carbon from organic matter decomposition. Matsutake was not associated with a particular soil chemistry compared to that of nearby sites where the fungus does not occur. The presence of a significant hemicellulose pool and the enzymes to degrade it indicates the potential for obtaining carbon from the soil rather than tree roots. PMID- 21984248 TI - Stimulation of methanotrophic growth in cocultures by cobalamin excreted by rhizobia. AB - Methanotrophs play a key role in the global carbon cycle, in which they affect methane emissions and help to sustain diverse microbial communities through the conversion of methane to organic compounds. To investigate the microbial interactions that cause positive effects on methanotrophs, cocultures were constructed using Methylovulum miyakonense HT12 and each of nine nonmethanotrophic bacteria, which were isolated from a methane-utilizing microbial consortium culture established from forest soil. Three rhizobial strains were found to strongly stimulate the growth and methane oxidation of M. miyakonense HT12 in cocultures. We purified the stimulating factor produced by Rhizobium sp. Rb122 and identified it as cobalamin. Growth stimulation by cobalamin was also observed for three other gammaproteobacterial methanotrophs. These results suggest that microbial interactions through cobalamin play an important role in methane oxidation in various ecosystems. PMID- 21984249 TI - Biosecurity-based interventions and strategies to reduce Campylobacter spp. on poultry farms. AB - The prevention and control of Campylobacter colonization of poultry flocks are important public health strategies for the control of human campylobacteriosis. A critical review of the literature on interventions to control Campylobacter in poultry on farms was undertaken using a systematic approach. Although the focus of the review was on aspects appropriate to the United Kingdom poultry industry, the research reviewed was gathered from worldwide literature. Multiple electronic databases were employed to search the literature, in any language, from 1980 to September 2008. A primary set of 4,316 references was identified and scanned, using specific agreed-upon criteria, to select relevant references related to biosecurity-based interventions. The final library comprised 173 references. Identification of the sources of Campylobacter in poultry flocks was required to inform the development of targeted interventions to disrupt transmission routes. The approach used generally involved risk factor-based surveys related to culture positive or -negative flocks, usually combined with a structured questionnaire. In addition, some studies, either in combination or independently, undertook intervention trials. Many of these studies were compromised by poor design, sampling, and statistical analysis. The evidence for each potential source and route of transmission on the poultry farm was reviewed critically, and the options for intervention were considered. The review concluded that, in most instances, biosecurity on conventional broiler farms can be enhanced and this should contribute to the reduction of flock colonization. However, complementary, non-biosecurity-based approaches will also be required in the future to maximize the reduction of Campylobacter-positive flocks at the farm level. PMID- 21984253 TI - Estrogen receptors and type 1 metabotropic glutamate receptors are interdependent in protecting cortical neurons against beta-amyloid toxicity. AB - We examined the interaction between estrogen receptors (ERs) and type 1 metabotropic glutamate receptors (mGlu1 receptors) in mechanisms of neurodegeneration/neuroprotection using mixed cultures of cortical cells challenged with beta-amyloid peptide. Both receptors were present in neurons, whereas only ERalpha but not mGlu1 receptors were found in astrocytes. Addition of 17beta-estradiol (17betaE2) protected cultured neurons against amyloid toxicity, and its action was mimicked by the selective ERalpha agonist, 1,3,5 tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) as well as by a cell-impermeable bovine serum albumin conjugate of 17betaE2. The selective ERbeta agonist, diarylpropionitrile (DPN), was only slightly neuroprotective. The mGlu1/5 receptor agonist, 3,5-dihydroxyphenylglycine (DHPG), was also neuroprotective against amyloid toxicity, and its action was abolished by the mGlu1 receptor antagonist, (3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-(cis-4-methoxycyclohexyl) methanone (JNJ 16259685). Neuroprotection by 17betaEpsilon2 or PPT (but not DPN) and DHPG was less than additive, suggesting that ERalpha and mGlu1 receptors activate the same pathway of cell survival. More important, neuroprotection by 17betaEpsilon2 was abolished not only by the ER antagonist fulvestrant (ICI 182,780) but also by JNJ 16259685, and neuroprotection by DHPG was abolished by ICI 182,780. ERalpha and mGlu1 receptors were also interdependent in activating the phosphatidylinositol-3-kinase pathway, and pharmacological blockade of this pathway abolished neuroprotection by 17betaE2, DHPG, or their combination. These data provide the first evidence that ERalpha and mGlu1 receptors critically interact in promoting neuroprotection, information that should be taken into account when the impact of estrogen on neurodegeneration associated with central nervous system disorders is examined. PMID- 21984254 TI - The LRRC26 protein selectively alters the efficacy of BK channel activators. AB - Large conductance, Ca(2+)-activated K channel proteins are involved in a wide range of physiological activities, so there is considerable interest in the pharmacology of large conductance calcium-activated K (BK) channels. One potent activator of BK channels is mallotoxin (MTX), which produces a very large hyperpolarizing shift of the voltage gating of heterologously expressed BK channels and causes a dramatic increase in the activity of BK channels in human smooth muscle cells. However, we found that MTX shifted the steady-state activation of BK channels in native parotid acinar cells by only 6 mV. This was not because the parotid BK isoform (parSlo) is inherently insensitive to MTX as MTX shifted the activation of heterologously expressed parSlo channels by 70 mV. Even though MTX had a minimal effect on steady-state activation of parotid BK channels, it produced an approximate 2-fold speeding of the channel-gating kinetics. The BK channels in parotid acinar cells have a much more hyperpolarized voltage activation range than BK channels in most other cell types. We found that this is probably attributable to an accessory protein, LRRC26, which is expressed in parotid glands: expressed parSlo + LRRC26 channels were resistant to the actions of MTX. Another class of BK activators is the benzimidazalones that includes 1,3-dihydro-1-(2-hydroxy-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl) 2H-benzimidazol-2-one (NS-1619). Although the LRRC26 accessory protein strongly inhibited the ability of MTX to activate BK channels, we found that it had only a small effect on the action of NS-1619 on BK channels. Thus, the LRRC26 BK channel accessory protein selectively alters the pharmacology of BK channels. PMID- 21984255 TI - Diflavin oxidoreductases activate the bioreductive prodrug PR-104A under hypoxia. AB - The clinical agent PR-104 is converted systemically to PR-104A, a nitrogen mustard prodrug designed to target tumor hypoxia. Reductive activation of PR-104A is initiated by one-electron oxidoreductases in a process reversed by oxygen. The identity of these oxidoreductases is unknown, with the exception of cytochrome P450 reductase (POR). To identify other hypoxia-selective PR-104A reductases, nine candidate oxidoreductases were expressed in HCT116 cells. Increased PR-104A cytotoxicity was observed in cells expressing methionine synthase reductase (MTRR), novel diflavin oxidoreductase 1 (NDOR1), and inducible nitric-oxide synthase (NOS2A), in addition to POR. Plasmid-based expression of these diflavin oxidoreductases also enhanced bioreductive metabolism of PR-104A in an anoxia specific manner. Diflavin oxidoreductase-dependent PR-104A metabolism was suppressed >90% by pan-flavoenzyme inhibition with diphenyliodonium chloride. Antibodies were used to quantify endogenous POR, MTRR, NDOR1, and NOS2A expression in 23 human tumor cell lines; however, only POR protein was detectable and its expression correlated with anoxic PR-104A reduction (r(2) = 0.712). An anti-POR monoclonal antibody was used to probe expression using human tissue microarrays; 13 of 19 cancer types expressed detectable POR with 21% of cores (185 of 874) staining positive; this heterogeneity suggests that POR is a useful biomarker for PR-104A activation. Immunostaining for carbonic anhydrase 9 (CAIX), reportedly an endogenous marker of hypoxia, revealed only moderate coexpression (9.6%) of both CAIX and POR across a subset of five cancer types. PMID- 21984256 TI - Wall shear stress distribution inside growing cerebral aneurysm. AB - BACKGROUND AND PURPOSE: Hemodynamic stimulation has been suggested to affect the growth of cerebral aneurysms. The present study examined the effects of intra aneurysmal hemodynamics on aneurysm growth. MATERIALS AND METHODS: Velocity profiles were measured for 2 cases of AcomA aneurysms. Realistically shaped models of these aneurysms were constructed, based on CT angiograms. Flow fields and WSS in the models were measured by using particle image velocimetry and LDV. In 1 case, hemodynamic changes were observed in 4 stages of growth over a 27 month period, whereas no development was observed in the other case. RESULTS: The growing model had a smaller and more stagnant recirculation area than that in the nongrowth model. The WSS was markedly reduced in the enlarging region in the growing models, whereas extremely low WSS was not found in the nongrowth model. In addition, a higher WSSG was consistently observed adjacent to the enlarging region during aneurysm growth. CONCLUSIONS: The results indicated that the flow structure of recirculation itself does not necessarily lead to high likelihood of cerebral aneurysm. However, WSSG and WSS were distinctly different between the 2 cases. Higher WSSG was found surrounding the growing region, and extremely low WSS was found at the growing region of the growing cerebral aneurysm. PMID- 21984257 TI - Assessment of dietary exposure related to dietary GI and fibre intake in a nutritional metabolomic study of human urine. AB - There is a need for a tool to assess dietary intake related to the habitual dietary glycaemic index (GI) and fibre in groups with large numbers of individuals. Novel metabolite-profiling techniques may be a useful approach when applied to human urine. In a long-term, controlled dietary intervention study, metabolomics were applied to assess dietary patterns. A targeted approach was used to evaluate the effects on urinary C-peptide excretion caused by the dietary treatments. Seventy-seven overweight subjects followed an 8-week low-calorie diet (LCD) and were then randomly assigned to a high-GI or low-GI diet for 6 month during which they completed 24-h urine collections at baseline (prior to the 8 week LCD) and after randomisation to the dietary intervention, at month 1, 3 and 6, respectively. Metabolite profiling in 24-h urine was performed by (1)H NMR and chemometrics. Partial least squares (PLS) analysis indicated that urinary formate could discriminate between high-GI and low-GI diets (correlation coefficient r = 0.82), and this finding was confirmed statistically (P = 0.01). PLS analysis also indicated that urinary hippurate could be associated with fibre intake, but this finding was not confirmed statistically. No associations between GI and urinary C peptide were found. Our results emphasise that application of metabolomics is useful in the assessment of dietary exposure related to dietary GI and fibre seen at group level in a nutritional metabolomic study of human urine. As our design allowed for large variations in individually selected food items, biomarkers identified at group level may be interpreted as more general and robust markers, largely not confounded with markers from single dietary factors. PMID- 21984258 TI - Benfotiamine increases glucose oxidation and downregulates NADPH oxidase 4 expression in cultured human myotubes exposed to both normal and high glucose concentrations. AB - The aim of the present work was to study the effects of benfotiamine (S benzoylthiamine O-monophosphate) on glucose and lipid metabolism and gene expression in differentiated human skeletal muscle cells (myotubes) incubated for 4 days under normal (5.5 mM glucose) and hyperglycemic (20 mM glucose) conditions. Myotubes established from lean, healthy volunteers were treated with benfotiamine for 4 days. Glucose and lipid metabolism were studied with labeled precursors. Gene expression was measured using real-time polymerase chain reaction (qPCR) and microarray technology. Benfotiamine significantly increased glucose oxidation under normoglycemic (35 and 49% increase at 100 and 200 MUM benfotiamine, respectively) as well as hyperglycemic conditions (70% increase at 200 MUM benfotiamine). Benfotiamine also increased glucose uptake. In comparison, thiamine (200 MUM) increased overall glucose metabolism but did not change glucose oxidation. In contrast to glucose, mitochondrial lipid oxidation and overall lipid metabolism were unchanged by benfotiamine. The expression of NADPH oxidase 4 (NOX4) was significantly downregulated by benfotiamine treatment under both normo- and hyperglycemic conditions. Gene set enrichment analysis (GSEA) showed that befotiamine increased peroxisomal lipid oxidation and organelle (mitochondrial) membrane function. In conclusion, benfotiamine increases mitochondrial glucose oxidation in myotubes and downregulates NOX4 expression. These findings may be of relevance to type 2 diabetes where reversal of reduced glucose oxidation and mitochondrial capacity is a desirable goal. PMID- 21984259 TI - Professional satisfaction of radiologists in Switzerland. AB - QUESTIONS UNDER STUDY: To gain insight into the determinants of radiologists' professional satisfaction in Switzerland. METHODS: Data from 254 members of the Swiss Society of Radiology (76% men) obtained in a questionnaire survey were analysed by logistic regression analysis using socio-demographic, person- and workplace-related factors as independent variables (determinants) and satisfaction at work as the outcome variable. RESULTS: In terms of person-related factors within a complex logistical regression model, radiologists with low occupational self-efficacy and especially those with low mental wellbeing were at elevated risk for low professional satisfaction, with the latter determinant being the strongest predictor in the whole model. Regarding work-related determinants, low career satisfaction and high workload increased the risk of low job satisfaction while working in a university hospital was a protection factor against low job satisfaction with private practice being the reference. A total of 42% of the respondents enjoyed their job more, and 19% enjoyed it less compared to five years previously, while 39% experienced no change. CONCLUSION: Despite high workload, time and economic pressure, the majority of radiologists were professionally satisfied at a high level, which had even increased within the last five years. However, to keep this level of job satisfaction, career possibilities, especially in private practices, have to be improved. Furthermore, the radiologists' important contribution to the diagnostic and therapeutic process has to be recognised professionally as well as economically. PMID- 21984260 TI - Passive smoking: the democratic right of nonsmokers to survive. PMID- 21984261 TI - Left ventricular diastolic dysfunction and increased left atrial volume predict arrhythmia recurrence in patients with atrial fibrillation. PMID- 21984262 TI - Functional characterization of an acidic SK(3) dehydrin isolated from an Opuntia streptacantha cDNA library. AB - Cactus pears are succulent plants of the Cactaceae family adapted to extremely arid, hot and cold environments, making them excellent models for the study of molecular mechanisms underlying abiotic stress tolerance. Herein, we report a directional cDNA library from 12-month-old cladodes of Opuntia streptacantha plants subjected to abiotic stresses. A total of 442 clones were sequenced, representing 329 cactus pear unigenes, classified into eleven functional categories. The most abundant EST (unigen 33) was characterized under abiotic stress. This cDNA of 905 bp encodes a SK(3)-type acidic dehydrin of 248 amino acids. The OpsDHN1 gene contains an intron inserted within the sequence encoding the S-motif. qRT-PCR analysis shows that the OpsDHN1 transcript is specifically accumulated in response to cold stress, and induced by abscisic acid. Over expression of the OpsDHN1 gene in Arabidopsis thaliana leads to enhanced tolerance to freezing treatment, suggesting that OpsDHN1 participates in freezing stress responsiveness. Generation of the first EST collection for the characterization of cactus pear genes constitutes a useful platform for the understanding of molecular mechanisms of stress tolerance in Opuntia and other CAM plants. PMID- 21984263 TI - Energy from residual waste. PMID- 21984264 TI - Transseptal catheter decompression of the left ventricle during extracorporeal membrane oxygenation. AB - Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can result in left ventricular distension and the development of pulmonary edema. We present the case of a 13-year-old girl who presented with cardiogenic shock. VA-ECMO was initiated, but after 6 days, severe left-ventricular distension resulted in decreased VA-ECMO flows. With guidance by bedside transesophageal echocardiography, a percutaneous atrial transseptal cannula was placed and connected to the venous circuit, thus decompressing the left ventricle. The patient improved, was weaned from VA-ECMO 5 days later, and was discharged from the hospital. Bedside transseptal catheter insertion is an effective method of left-ventricular decompression. PMID- 21984265 TI - Hypoplastic left heart syndrome, restrictive patent foramen ovale, and pulmonary valve stenosis: an unusual combination. AB - An infant presented with a rare combination of hypoplastic left heart syndrome, restricted patent foramen ovale, and moderately dysplastic pulmonary valve. In preparation for heart transplantation, bilateral pulmonary artery banding was performed to protect the pulmonary vasculature. PMID- 21984266 TI - Infectious bursal disease DNA vaccination conferring protection by delayed appearance and rapid clearance of invading viruses. AB - The present study was undertaken to determine the kinetics of viral load and immune response in protection against infectious bursal disease virus (IBDV) by DNA vaccination. Chickens were DNA-vaccinated and challenged with IBDV one week after the third vaccination. Tissues were collected at 12 hours postinfection (HPI), 1 day postinfection (DPI), 3, 5, 7 and 10 DPI. The vaccinated chickens had less viral RNA, with delayed appearance and shorter duration in the bursa of Fabricius, spleen, and cecal tonsil than the challenged control chickens. Their ELISA and neutralizing antibody titers were decreased at 12 HPI and significantly lower (P < 0.05) than those in the challenged control chickens at later time points. Their spleen IFNgamma expression was up-regulated compared to that in the DNA-vaccinated chickens without IBDV challenge. These results indicate that DNA vaccination confers protection against IBDV challenge by delayed appearance and rapid clearance of the invading viruses. PMID- 21984267 TI - Antigenicity, animal protective effect and genetic characteristics of candidate vaccine strains of enterovirus 71. AB - Enterovirus 71 (EV71) is one of the major causative agents of hand, foot and mouth disease. Recently, several EV71 inactivated vaccine candidates have been development in mainland China. To compare the antigenicity and genetic characteristics of different candidate vaccine strains for EV71, the genomes of 11 EV71 strains were sequenced. The cross-protection capacities were determined by neutralizing antibody test and were further assessed in neonatal mice. The results showed 93.0%-99.8% genome homology of the VP1 regions, but their cross neutralization capacities varied. These results showed that vaccine strains with good cross-neutralization capacities had the potential to be vaccine strains. PMID- 21984268 TI - Discovery of novel human acrosin inhibitors by virtual screening. AB - Human acrosin is an attractive target for the discovery of male contraceptive drugs. For the first time, structure-based drug design was applied to discover structurally diverse human acrosin inhibitors. A parallel virtual screening strategy in combination with pharmacophore-based and docking-based techniques was used to screen the SPECS database. From 16 compounds selected by virtual screening, a total of 10 compounds were found to be human acrosin inhibitors. Compound 2 was found to be the most potent hit (IC(50) = 14 MUM) and its binding mode was investigated by molecular dynamics simulations. The hit interacted with human acrosin mainly through hydrophobic and hydrogen-bonding interactions, which provided a good starting structure for further optimization studies. PMID- 21984269 TI - Pain disorders and erythromelalgia caused by voltage-gated sodium channel mutations. AB - Voltage-gated sodium channels play a pivotal role in pain transmission. They are widely expressed in nociceptive neurons, and participate in the generation of action potentials. Alteration in ionic conduction of these channels causes abnormal electrical firing, thus renders neurons hyperexcitable. So far, mutations in the Na(v)1.7 sodium channel, which is expressed in the dorsal root ganglia cells and sympathetic neurons, have been described to cause perturbations in pain sensation. Until recently, gain-of-function Na(v)1.7 mutations were known to cause two neuropathic pain syndromes: inherited erythromelalgia and paroxysmal extreme pain syndrome. These syndromes are inherited in a dominant trait; they usually begin in childhood or infancy, and are characterized by attacks of severe neuropathic pain accompanied with autonomic symptoms. Recently, small fiber neuropathy and chronic nonparoxysmal pain have been described in patients harboring gain-of-function mutations in Na(v)1.7 channel. Loss-of-function mutations in Na(v)1.7 are extremely rare, and invariably cause congenital inability to perceive pain. PMID- 21984271 TI - Iron-based redox centres of reductase and oxygenase components of phenol hydroxylase from A. radioresistens: a redox chain working at highly positive redox potentials. AB - This is the first report of the direct electrochemistry of the reductase (PHR) and oxygenase (PHO) components of phenol hydroxylase from Acinetobacter radioresistens S13 studied by cyclic and differential pulse voltammetry. The PHR contains one 2Fe2S cluster and one FAD that mediate the transfer of electrons from NAD(P)H to the non-heme diiron cluster of PHO. Cyclic and differential pulse voltammetry (CV and DPV) on glassy carbon showed two redox pairs with midpoint potentials at +131.5 +/- 13 mV and -234 +/- 3 mV versus normal hydrogen electrode (NHE). The first redox couple is attributed to the FeS centre, while the second one corresponds to free FAD released by the protein. DPV scans on native and guanidinium chloride treated PHR highlighted the presence of a split signal (DeltaE ~ 100 mV) attributed to heterogeneous properties of the 2Fe2S cluster interacting with the electrode, possibly due to the presence of two protein conformers and consistently with the large peak-to-peak separation and the peak broadening observed in CV. DPV experiments on gold electrodes performed on PHO confirm a consistently higher reduction potential at +396 mV vs. NHE. The positive redox potentials measured by direct electrochemistry for the FeS cluster in PHR and for the non-heme diiron cluster of PHO show that the entire phenol hydroxylase system works at higher potentials than those reported for structurally similar enzymes, for example methane monooxygenases. PMID- 21984270 TI - Susceptibility of Pseudomonas aeruginosa urinary tract isolates and influence of urinary tract conditions on antibiotic tolerance. AB - Pseudomonas aeruginosa is an opportunistic human pathogen, which can cause severe urinary tract infections (UTIs). Because of the high intrinsic antibiotic resistance of P. aeruginosa and its ability to develop new resistances during antibiotic treatment, these infections are difficult to eradicate. The antibiotic susceptibility of 32 P. aeruginosa isolates from acute and chronic UTIs were analysed under standardized conditions showing 19% multi-drug resistant strains. Furthermore, the antibiotic tolerance of two P. aeruginosa strains to ciprofloxacin and tobramycin was analysed under urinary tract-relevant conditions which considered nutrient composition, biofilm growth, growth phase, and oxygen concentration. These conditions significantly enhance the antibiotic tolerance of P. aeruginosa up to 6000-fold indicating an adaptation of the bacterium to the specific conditions present in the urinary tract. This reversible phenomenon is possibly due to the increased formation of persister cells and is based on iron limitation in artificial urine. The results suggest that the general high antibiotic resistance of P. aeruginosa urinary tract isolates together with the increasing tolerance of P. aeruginosa grown under urinary tract conditions decrease the efficiency of antibiotic treatment of UTIs. PMID- 21984272 TI - High prevalence of methicillin-resistant Staphylococcus aureus among residents and staff of long-term care facilities, involving joint and parallel evolution. AB - Six long-term care facilities were surveyed for methicillin-resistant Staphylcoccus aureus (MRSA). Among 191 residents, 14% were carriers; 1 strain predominated (ST5-SCCmec II). Among 132 staff members, 11% were positive; 2 strains predominated (ST5-SCCmec II, ST8-SCCmec IV). All strains were Panton Valentine leukocidin-negative. The epidemiology of MRSA among residents and staff involved joint and parallel evolution. PMID- 21984274 TI - Bowel "infarction" in a postpartum patient. PMID- 21984283 TI - Cytokinesis, ploidy and aneuploidy. AB - Cytokinesis is the last step of cell division that physically separates the daughter cells. As such, it ensures the proper inheritance of both nuclear and cytoplasmic contents. Accomplishment of cytokinesis in eukaryotes is dictated by several key events: establishment of the division plane, furrow ingression through contraction of an actomyosin ring and abscission via membrane fusion. Most mammalian somatic cells are diploid. Polyploidy can result from cytokinesis failure and may contribute to the development of pathologies such as cancer. However, polyploidy is essential for cellular differentiation and function in some contexts (eg hepatocytes, megakaryocytes and others). Consequently, the degree of ploidy and the achievement of cytokinesis must be tightly regulated throughout an organism and among different cell types. In this review we will highlight several examples of normal and pathological polyploidy, focusing on those caused by a controlled failure or dysregulation of cytokinesis, respectively. Last, we propose therapeutic routes to control cytokinesis to restore or block cell division. PMID- 21984284 TI - Too many journals--too little good research. PMID- 21984285 TI - Professional autonomy demands professional cooperation. PMID- 21984286 TI - [Vaginal bleeding also alarming]. PMID- 21984287 TI - [Stroke neurology and interdisciplinarity]. PMID- 21984288 TI - [Diagnosis of neck bias in children-bad practice?]. PMID- 21984289 TI - [Stroke requires specialized treatment]. PMID- 21984290 TI - [Intestinal auto-intoxication--still a current disease mechanism?]. PMID- 21984291 TI - [Peter F. Hjort's contribution to palliative medicine]. PMID- 21984292 TI - [Do differences in referral rates threaten the goal of equity in health care?]. AB - BACKGROUND: In comparison with the national average, and particularly in comparison with the region Helse Vest, which it forms part of, Sogn og Fjordane county has a high level of specialist health care utilization. Apart from the fact that it has two small community hospitals, little is known that could explain this county's high expenditure, and especially whether contrasts exist between its municipalities. MATERIALS AND METHODS: Based on data from the National Patient Registry and the administrative hospital registry DIPS for the year 2009, age and sex-adjusted utilization rates are compared at municipality level and at the level of the primary health care doctor. RESULTS: Marked contrasts between the municipalities were observed, both with respect to contact and DRG point rates. A further comparison of three comparable municipalities with different utilization rates revealed high and concurrent differences in referral rates between primary health doctors in the three municipalities. INTERPRETATION: The high and diverse utilization rates of specialist health care between municipalities in Sogn og Fjordane seem to be associated with correspondingly high and even more pronounced differences in referral rates from primary health care doctors. PMID- 21984293 TI - [Treating morbid obesity with laparoscopic biliopancreatic diversion with duodenal switch]. AB - BACKGROUND: Biliopancreatic diversion with duodenal switch is used in the treatment of morbid obesity. Few centres perform the procedure laparoscopically. We aimed to evaluate the perioperative outcomes and weight loss after laparoscopic duodenal switch. MATERIAL AND METHODS: All patients operated with biliopancreatic diversion with duodenal switch at the Centre for Morbid Obesity at Oslo University Hospital (2004-2009) were included. The perioperative period was defined as within 30 days of surgery. RESULTS: A total of 48 patients were operated, all laparoscopically. Median preoperative BMI was 54 kg/m2 (range 41 88), and 33 patients (69 %) were women. Ten patients (21 %) were operated in two steps: first gastric sleeve and later duodenal switch. Median operation time was 200 minutes (100-658). Twelve patients (25 %) had complications, four (8 %) were reoperated, and one died. Median postoperative hospital stay was three (1-56) days. After two years, median BMI was 32 kg/m2 (24-45), median weight loss 39 % (22-60) and median excess BMI (> 25 kg/m2) loss 73 % (43-106). INTERPRETATION: Duodenal switch was applied in a minority of patients operated for morbid obesity. The procedure can be performed laparoscopically with a short hospital stay and leads to a substantial weight loss. Perioperative morbidity was high and was comparable to the results from other series. PMID- 21984294 TI - [Follow-up after bariatric surgery]. AB - BACKGROUND: The number of bariatric surgical procedures in Norway is increasing. Patients who undergo bariatric surgery may experience surgical, medical and nutritional complications. Follow-up of these patients is therefore important. METHODS: The article is based on non-systematic literature searches in PubMed and on the clinical experience of the authors. RESULTS: Bariatric surgery induces significant and sustained weight loss and improves obesity-related disorders. Gastric bypass is the most commonly performed bariatric procedure in Norway. This procedure is associated with a 30-day mortality of below 0.5 %, while severe complications occur in approximately 5 % of patients. Late complications include internal herniation, intestinal ulcers and gallbladder disease. After surgery all patients are given iron, vitamin D/calcium and vitamin B12 supplements to prevent vitamin and mineral deficiencies. Gastrointestinal symptoms and postprandial hypoglycaemia after surgery can be improved by dietary modifications, and the need for anti-diabetic and blood pressure lowering medications is reduced. Dose adjustment of other medications may also be necessary. Pregnancy is not recommended during the first year after bariatric surgery. Many patients need plastic surgery after the operation. INTERPRETATION: Complications after bariatric surgery may manifest in the long term. Regular follow-up is required. General practitioners should be responsible for follow-up in the long term, and should be familiar with common and serious complications as well as normal symptomatology after bariatric surgery. PMID- 21984295 TI - [Denosumab for treatment of postmenopausal osteoporosis]. AB - BACKGROUND: Treatment with bisphosphonates reduces the risk of new fractures and is the treatment of choice for osteoporosis. Denosumab inhibits bone resorption via a different mechanism than bisphosphonates, and is a new option in the treatment of osteoporosis. In this paper we give an overview of the mode of action and clinical effects. MATERIAL AND METHODS: The paper is based on a non systematic literature search in Pubmed/Medline. RESULTS: Denosumab is a human monoclonal antibody to receptor-activated nuclear factor kappa B (RANKL), a member of the TNF family that is formed in the osteoblast. Binding to RANKL results in reduced recruitment and activity of osteoclasts. Denosumab 60 mg given subcutaneously every six months is shown to inhibit bone resorption to a greater degree than bisphosphonates. In a three-year study of 7,868 women with postmenopausal osteoporosis, a reduction in the relative risk of vertebral, non vertebral and hip fractures compared to placebo was found (68. 20 and 40 %, correspondingly). In the clinical trials with denosumab, the safety profile was similar to placebo, except for a slightly higher incidence of cellulitis and exanthema. Denosumab has also shown promising skeletal effects in the treatment of cancer and rheumatoid arthritis. INTERPRETATION: Treatment with denosumab has an effect on postmenopausal osteoporosis and may be an alternative to treatment with bisphosphonates. There are few adverse effects and it is simple to administer. PMID- 21984296 TI - [A young woman with kidney failure]. PMID- 21984297 TI - [Dangerous herbs?]. PMID- 21984299 TI - Millennium Development Goals for health--will we reach them by 2015? PMID- 21984300 TI - Reproductive health--the millennium goal farthest from being achieved. PMID- 21984301 TI - The battle against HIV is not over--invest locally. PMID- 21984302 TI - It is dangerous to become a mother. PMID- 21984303 TI - [Poison control center 50 years--treatment of poisoning then and now]. PMID- 21984306 TI - Impact of hysterectomy and bilateral oophorectomy prevalence on rates of cervical, uterine, and ovarian cancer among American Indian and Alaska Native women, 1999-2004. AB - OBJECTIVE: To present more accurate incidence rates of cervical, uterine, and ovarian cancer by geographic region in American Indian/Alaska Native (AI/AN) women. METHODS: The authors used data from central cancer registries linked to Indian Health Service (IHS) patient registration database, the Behavioral Risk Factor Surveillance System, IHS National Data Warehouse, and the National Hospital Discharge Survey. Cancer incidence rates were adjusted for hysterectomy and oophorectomy prevalence and presented by region for non-Hispanic White (NHW) and AI/AN women. RESULTS: AI/AN women had a higher prevalence of hysterectomy (23.1%) compared with NHW women (20.9%). Correcting cancer rates for population at-risk significantly increased the cancer incidence rates among AI/AN women: 43% for cervical cancer, 67% for uterine cancer, and 37% for ovarian cancer. Risk correction led to increased differences in cervical cancer incidence between AI/AN and NHW women in certain regions. CONCLUSIONS: Current reporting of cervical, uterine, and ovarian cancer underestimates the incidence in women at risk and can affect the measure of cancer disparities. Improved cancer surveillance using methodology to correct for population-at-risk may better inform disease control priorities for AI/AN populations. PMID- 21984307 TI - Associations of whole-blood fatty acids and dietary intakes with prostate cancer in Jamaica. AB - OBJECTIVE: To investigate the association of whole-blood fatty acids and reported intakes of fats with risk of prostate cancer (PCa). DESIGN: Case-control study of 209 men 40-80 years old with newly diagnosed, histologically confirmed prostate cancer and 226 cancer-free men attending the same urology clinics. Whole-blood fatty acid composition (mol%) was measured by gas chromatography and diet assessed by food frequency questionnaire. RESULTS: High whole-blood oleic acid composition (tertile 3 vs. tertile 1: OR, 0.37; CI, 0.14-0.0.98) and moderate palmitic acid proportions (tertile 2: OR, 0.29; CI, 0.12-0.70) (tertile 3: OR, 0.53; CI, 0.19-1.54) were inversely related to risk of PCa, whereas men with high linolenic acid proportions were at increased likelihood of PCa (tertile 3 vs. tertile 1: OR, 2.06; 1.29-3.27). Blood myristic, stearic and palmitoleic acids were not associated with PCa. Higher intakes of dietary MUFA were inversely related to prostate cancer (tertile 3 vs. tertile 1: OR, 0.39; CI 0.16-0.92). The principal source of dietary MUFA was avocado intake. Dietary intakes of other fats were not associated with PCa. CONCLUSIONS: Whole-blood and dietary MUFA reduced the risk of prostate cancer. The association may be related to avocado intakes. High blood linolenic acid was directly related to prostate cancer. These associations warrant further investigation. PMID- 21984308 TI - Structural dynamics of low-symmetry Au nanoparticles stimulated by electron irradiation. PMID- 21984309 TI - Economical and effective sulfide catalysts for dye-sensitized solar cells as counter electrodes. AB - Molybdenum sulfide (MoS(2)) and tungsten sulfide (WS(2)) are proposed as counter electrode (CE) catalysts in a I(3)(-)/I(-) and T(2)/T(-) based dye-sensitized solar cells (DSCs) system. The I(3)(-)/I(-) based DSCs using MoS(2) and WS(2) CEs achieved power conversion efficiencies of 7.59% and 7.73%, respectively. PMID- 21984311 TI - Politeness and social signals. AB - In the literature, politeness has been researched within many disciplines. Although Brown and Levinson's theory of politeness (1978, 1987) is often cited, it is primarily a linguistic theory and has been criticized for its lack of generalizability to all cultures. Consequently, there is a need for a more comprehensive approach to understand and explain politeness. We suggest applying a social signal framework that considers politeness as a communicative state. By doing so, we aim to unify and explain politeness and its corresponding research and identify further research needed in this area. PMID- 21984310 TI - Toward operational architectonics of consciousness: basic evidence from patients with severe cerebral injuries. AB - Although several studies propose that the integrity of neuronal assemblies may underlie a phenomenon referred to as awareness, none of the known studies have explicitly investigated dynamics and functional interactions among neuronal assemblies as a function of consciousness expression. In order to address this question, EEG operational architectonics analysis (Fingelkurts and Fingelkurts 2001, 2008) was conducted in patients in minimally conscious (MCS) and vegetative states (VS) to study the dynamics of neuronal assemblies and operational synchrony among them as a function of consciousness expression. We found that in minimally conscious patients and especially in vegetative patients neuronal assemblies got smaller, their life span shortened and they became highly unstable. Furthermore, we demonstrated that the extent/volume and strength of operational synchrony among neuronal assemblies was smallest or even absent in VS patients, intermediate in MCS patients, and highest in healthy fully conscious subjects. All findings were similarly observed in EEG alpha as well as beta1 and beta2 frequency oscillations. The presented results support the basic tenets of operational architectonics theory of brain-mind functioning and suggest that EEG operational architectonics analysis may provide an objective and accurate means of assessing signs of (un)consciousness in patients with severe brain injuries. Therefore, this methodological approach may complement the existing "gold standard" of behavioral assessment of this population of challenging patients and inform the diagnostic and treatment decision-making processes. PMID- 21984312 TI - Neuroanatomical changes in a mouse model of early life neglect. AB - Using a novel mouse model of early life neglect and abuse (ENA) based on maternal separation with early weaning, George et al. (BMC Neurosci 11:123, 2010) demonstrated behavioral abnormalities in adult mice, and Bordner et al. (Front Psychiatry 2(18):1-18, 2011) described concomitant changes in mRNA and protein expression. Using the same model, here we report neuroanatomical changes that include smaller brain size and abnormal inter-hemispheric asymmetry, decreases in cortical thickness, abnormalities in subcortical structures, and white matter disorganization and atrophy most severely affecting the left hemisphere. Because of the similarities between the neuroanatomical changes observed in our mouse model and those described in human survivors of ENA, this novel animal model is potentially useful for studies of human ENA too costly or cumbersome to be carried out in primates. Moreover, our current knowledge of the mouse genome makes this model particularly suited for targeted anatomical, molecular, and pharmacological experimentation not yet possible in other species. PMID- 21984313 TI - Aseptic loosening of total hip replacement presenting as an anterior thigh mass. AB - Aseptic loosening is one of the commonest complications of total hip replacement that can cause pain and instability. The chronic inflammatory response to the wear debris from the polyethylene or metal can cause osteolysis and implant failure. We report a case of aseptic loosening of the hip, presented with a swelling over the anterior thigh without any pain or instability in the joint. This mass was a foreign body granuloma formed secondary to the polyethylene wear debris due to the instability of the polyethylene in the metal shell. The patient underwent successful revision hip arthroplasty after the removal of the foreign body granuloma. PMID- 21984314 TI - Effects of chloroplast dysfunction on mitochondria: white sectors in variegated leaves have higher mitochondrial DNA levels and lower dark respiration rates than green sectors. AB - Co-ordination between plastids and mitochondria is so essential that there should be extensive inter-organellar crosstalk during development of plant cells. Indeed, chloroplast dysfunction in white leaves of plastid ribosome-deficient mutant barley, albostrians, is reportedly accompanied by increases in the levels of mitochondrial DNA and mitochondrial transcripts, suggesting that (i) developmental/physiological status of plastids (or heterotrophic growth condition of albino leaves) can affect the status of mitochondrial genome, and (ii) the function of the affected mitochondria may also be up-regulated accordingly. However, functional aspects of the mitochondria affected by chloroplast dysfunction have not yet been examined in detail. Here, we examined the effects of chloroplast dysfunction on mitochondrial DNA level and dark respiration rate, by comparing white and green sectors within individual variegated leaves, using 12 ornamental plants as experimental materials. The pattern of leaf variegation differed from species to species, suggesting that different mechanisms were involved in the formation of white sectors in different species. Quantitative hybridization analysis revealed that mitochondrial DNA levels were generally higher in white sectors than in green sectors. In spite of the elevated mitochondrial DNA levels, however, dark respiration rates in white sectors were generally lower than those in green sectors. Several possible mechanisms for elevation of mitochondrial DNA level and suppression of dark respiration rates in white sectors are discussed. PMID- 21984315 TI - Robotic presacral neurectomy - technique and results. AB - BACKGROUND: The feasibility, safety and outcomes of robotic presacral neurectomy were evaluated. METHODS: A retrospective analysis was performed of 33 patients with midline chronic pelvic pain, who underwent robotic presacral neurectomy. Data were collected during the period March 2004-March 2010. RESULTS: All patients underwent robotic presacral neurectomy and additional robotic procedures. Mean operating time for robotic presacral neurectomy was 5.8 (range 4.4-6.9) min. Mean blood loss, including concomitant procedures, was 39 (range 15 150) ml. Most patients were discharged the same day (60%) and mean hospital stay was 0.39 (range 0-2) days. There were no conversions or intra-operative complications. There were two postoperative complications: one pelvic abscess and one Clostridium difficile colitis. Pain improvement was reported by 73% (22/30) of patients. CONCLUSION: Robotic presacral neurectomy is safe and feasible, resulting in improvement of pelvic pain in selected patients. PMID- 21984316 TI - Multimodality imaging manifestations of the Meckel diverticulum in children. AB - Meckel diverticulum is the most common congenital abnormality of the gastrointestinal (GI) tract, occurring in approximately 2% of the general population. The lifetime complication rate from a Meckel diverticulum is 0.5%-2%. The most common complications include bleeding, obstruction, inflammation and perforation. However, the clinical manifestations of a Meckel diverticulum are frequently nonspecific. As a result, complications secondary to Meckel diverticulitis can mimic a variety of more common intra-abdominal processes, such as appendicitis, inflammatory bowel disease and any other cause of small bowel inflammation or obstruction. The radiologist should be aware of potential manifestations of the disease on different imaging modalities. In this pictorial essay, we illustrate several complications related to the Meckel diverticulum, in multiple modalities. PMID- 21984317 TI - Disseminated subarachnoid chordoma: long-term favorable follow-up of a pediatric patient. AB - We describe a case of extraosseous chordoma disseminated in the subarachnoid space with favorable long-term follow-up. During work-up of headaches in a 13 year-old girl, MRI revealed multiple cystic subarachnoid masses in the posterior fossa and spinal canal. She underwent posterior fossa craniectomy and was found to have multicentric subarachnoid chordomas with positive CSF cytology. Six years after the operation and radiotherapy, the girl is without neurological deficits despite persistent multiple subarachnoid cystic masses. PMID- 21984321 TI - Transnasal pharyngoscopy to assist nasobiliary tube placement: a simple technique to avoid injury to the patient, endoscopist, and endoscope. PMID- 21984318 TI - Relative contributions of local cell and passing fiber activation and silencing to changes in thalamic fidelity during deep brain stimulation and lesioning: a computational modeling study. AB - Deep brain stimulation (DBS) and lesioning are two surgical techniques used in the treatment of advanced Parkinson's disease (PD) in patients whose symptoms are not well controlled by drugs, or who experience dyskinesias as a side effect of medications. Although these treatments have been widely practiced, the mechanisms behind DBS and lesioning are still not well understood. The subthalamic nucleus (STN) and globus pallidus pars interna (GPi) are two common targets for both DBS and lesioning. Previous studies have indicated that DBS not only affects local cells within the target, but also passing axons within neighboring regions. Using a computational model of the basal ganglia-thalamic network, we studied the relative contributions of activation and silencing of local cells (LCs) and fibers of passage (FOPs) to changes in the accuracy of information transmission through the thalamus (thalamic fidelity), which is correlated with the effectiveness of DBS. Activation of both LCs and FOPs during STN and GPi-DBS were beneficial to the outcome of stimulation. During STN and GPi lesioning, effects of silencing LCs and FOPs were different between the two types of lesioning. For STN lesioning, silencing GPi FOPs mainly contributed to its effectiveness, while silencing only STN LCs did not improve thalamic fidelity. In contrast, silencing both GPi LCs and GPe FOPs during GPi lesioning contributed to improvements in thalamic fidelity. Thus, two distinct mechanisms produced comparable improvements in thalamic function: driving the output of the basal ganglia to produce tonic inhibition and silencing the output of the basal ganglia to produce tonic disinhibition. These results show the importance of considering effects of activating or silencing fibers passing close to the nucleus when deciding upon a target location for DBS or lesioning. PMID- 21984323 TI - Timing of endoscopy in high-risk patients with nonvariceal upper gastrointestinal bleeding. PMID- 21984325 TI - Giant colonic ulcer and pseudopolyps in an immunodepressed patient. PMID- 21984328 TI - Tocilizumab-induced intestinal injury. PMID- 21984330 TI - Feasibility of repeated use of the Health Risk Appraisal for Older people system as a health promotion tool in community-dwelling older people: retrospective cohort study 2001-05. PMID- 21984331 TI - Another new tool for the diagnostic bronchoscopist. PMID- 21984332 TI - Publics in the making: mediating different methods of engagement and the publics these construct : commentary on: "Technologies of democracy: experiments and demonstrations". AB - The potential for public engagement to democratise science has come under increasing scrutiny amid concerns that conflicting motivations have led to confusion about what engagement means to those who mediate science and publics. This raises important yet relatively unexplored questions regarding how publics are constituted by different forms of engagement used by intermediary scholars and other actors. It is possible to identify at least two possible 'rationalities of mediation' that mobilise different versions of the public and the roles they are assumed to play, as 'citizens' or 'users', in discussions around technology. However, combinations of rationalities are found in practice and these have significant implications for the 'new' scientific democracy. PMID- 21984333 TI - Negotiating plausibility: intervening in the future of nanotechnology. AB - The national-level scenarios project NanoFutures focuses on the social, political, economic, and ethical implications of nanotechnology, and is initiated by the Center for Nanotechnology in Society at Arizona State University (CNS ASU). The project involves novel methods for the development of plausible visions of nanotechnology-enabled futures, elucidates public preferences for various alternatives, and, using such preferences, helps refine future visions for research and outreach. In doing so, the NanoFutures project aims to address a central question: how to deliberate the social implications of an emergent technology whose outcomes are not known. The solution pursued by the NanoFutures project is twofold. First, NanoFutures limits speculation about the technology to plausible visions. This ambition introduces a host of concerns about the limits of prediction, the nature of plausibility, and how to establish plausibility. Second, it subjects these visions to democratic assessment by a range of stakeholders, thus raising methodological questions as to who are relevant stakeholders and how to activate different communities so as to engage the far future. This article makes the dilemmas posed by decisions about such methodological issues transparent and therefore articulates the role of plausibility in anticipatory governance. PMID- 21984335 TI - Modeling the dynamics of woody plant-herbivore interactions with age-dependent toxicity. AB - In this paper we study the effects that woody plant chemical defenses may have on interactions between boreal hares that in winter feed almost entirely on twigs. We focus particularly on the fact that toxin concentration often varies with the age of twig segments. The model incorporates the fact that the woody internodes of the youngest segments of the twigs of the deciduous angiosperm species that these hares prefer to eat are more defended by toxins than the woody internodes of the older segments that subtend and support the younger segments. Thus, the per capita daily intake of the biomass of the older segments of twigs by hares is much higher than their intake of the biomass of the younger segments of twigs. This age-dependent toxicity of twig segments is modeled using age-structured model equations which are reduced to a system of delay differential equations involving multiple delays in the woody plant-hare dynamics. A novel aspect of the modeling was that it had to account for mortality of non-consumed younger twig segment biomass when older twig biomass was bitten off and consumed. Basic mathematical properties of the model are established together with upper and lower bounds on the solutions. Necessary and sufficient conditions are found for the linear stability of the equilibrium in which the hare is extinct, and sufficient conditions are found for the global stability of this equilibrium. Numerical simulations confirmed the analytical results and demonstrated the existence of limit cycles over ranges of parameters reasonable for hares browsing on woody vegetation in boreal ecosystems. This showed that age dependence in plant chemical defenses has the capacity to cause hare-plant population cycles, a new result. PMID- 21984336 TI - A coordination polymer of (Ph3P)AuCl prepared by post-synthetic modification and its application in 1-hexene/n-hexane separation. AB - PCM-10 is a porous phosphine coordination material based on Ca(II) and tris(p carboxylated) triphenylphosphine. The material provides a unique 3-dimensional surface of P(III) Lewis base sites, which is ideal for post-synthetic functionalization. The addition of Au(I) yields an advanced material that can selectively adsorb 1-hexene over n-hexane at room temperature. PMID- 21984337 TI - Toll-like receptor-2 and interleukin-6 mediate cardiomyocyte protection from apoptosis during Trypanosoma cruzi murine infection. AB - Local innate immunity plays a key role in initiating and coordinating homeostatic and defense responses in the heart. We have previously reported that the cardiotropic parasite Trypanosoma cruzi, the etiological agent of Chagas disease, protects cardiomyocytes against growth factor deprivation-induced apoptosis. In this study, we investigated cardiomyocyte innate immune response to T. cruzi infection and its role in cellular protection from apoptosis. We found that Toll like receptor (TLR) 2-expressing cells were strongly increased by the parasite in BALB/c neonatal mouse cardiomyocyte cultures. Using a dominant-negative system, we showed that TLR2 mediated cardiomyocyte survival and the secretion of interleukin (IL) 6, which acted as an essential anti-apoptotic factor. Moreover, IL6 released by infected cells, as well as the recombinant bioactive cytokine, induced the phosphorylation of the signal transducers and activators of transcription-3 (STAT3) in cultured cardiomyocytes. In accord with the in vitro results, during the acute phase of the infection, TLR2 expression increased 2.9 fold and the anti-apoptotic factor Bcl-2 increased 4.5-fold in the cardiac tissue. We have clearly shown a cross-talk between the intrinsic innate response of cardiomyocytes and the pro-survival effect evoked by the parasite. PMID- 21984338 TI - Carbon nanotube wires and cables: near-term applications and future perspectives. AB - Wires and cables are essential to modern society, and opportunities exist to develop new materials with reduced resistance, mass, and/or susceptibility to fatigue. This article describes how carbon nanotubes (CNTs) offer opportunities for integration into wires and cables for both power and data transmission due to their unique physical and electronic properties. Macroscopic CNT wires and ribbons are presently shown as viable replacements for metallic conductors in lab scale demonstrations of coaxial, USB, and Ethernet cables. In certain applications, such as the outer conductor of a coaxial cable, CNT materials may be positioned to displace metals to achieve substantial benefits (e.g. reduction in cable mass per unit length (mass/length) up to 50% in some cases). Bulk CNT materials possess several unique properties which may offer advantages over metallic conductors, such as flexure tolerance and environmental stability. Specifically, CNT wires were observed to withstand greater than 200,000 bending cycles without increasing resistivity. Additionally, CNT wires exhibit no increase in resistivity after 80 days in a corrosive environment (1 M HCl), and little change in resistivity with temperature (<1% from 170-330 K). This performance is superior to conventional metal wires and truly novel for a wiring material. However, for CNTs to serve as a full replacement for metals, the electrical conductivity of CNT materials must be improved. Recently, the conductivity of a CNT wire prepared through simultaneous densification and doping has exceeded 1.3 * 10(6) S/m. This level of conductivity brings CNTs closer to copper (5.8 * 10(7) S/m) and competitive with some metals (e.g. gold) on a mass normalized basis. Developments in manipulation of CNT materials (e.g. type enrichment, doping, alignment, and densification) have shown progress towards this goal. In parallel with efforts to improve bulk conductivity, integration of CNT materials into cabling architectures will require development in electrical contacting. Several methods for contacting bulk CNT materials to metals are demonstrated, including mechanical crimping and ultrasonic bonding, along with a method for reducing contact resistance by tailoring the CNT-metal interface via electroless plating. Collectively, these results summarize recent progress in CNT wiring technologies and illustrate that nanoscale conductors may become a disruptive technology in cabling designs. PMID- 21984339 TI - Let-7c functions as a metastasis suppressor by targeting MMP11 and PBX3 in colorectal cancer. AB - Accumulating evidence shows that microRNAs, functioning as either oncogenes or tumour suppressors by negatively regulating downstream target genes that are actively involved in tumour initiation and progression, may be promising biomarkers and therapy targets. Data mining through a microRNA chip database indicated that let-7c may be associated with tumour metastasis. Here, we confirmed that down-regulation of let-7c in primary cancer tissues was significantly associated with metastases, advanced TNM stages and poor survival of colorectal cancer patients. Moreover, ectopic expression of let-7c in a highly metastatic Lovo cell line remarkably suppressed cell migration and invasion in vitro by the down-regulation of K-RAS, MMP11 and PBX3, as well as tumour growth and metastases in vivo, whereas inhibition of let-7c in low-metastatic HT29 cells increased cell motility and invasion by the enhanced gene expression of K-RAS, MMP11 and PBX3. Interestingly, the luciferase reporters' activities with the 3' UTRs of K-RAS, MMP11 and PBX3 were inhibited significantly by let-7c. Importantly, rescue experiments involving the over-expression of these genes without their 3'-UTRs completely reversed the effects of let-7c on tumour metastasis, both in vitro and in vivo. Finally, the levels of let-7c were inversely correlated with those of MMP11 and PBX3, but not with those of K-RAS. Taken together, these results demonstrate that let-7c, apart from its tumour growth suppression role, also functions as a tumour metastasis suppressor in colorectal cancer by directly destabilizing the mRNAs of MMP11 and PBX3 at least. PMID- 21984340 TI - Compounds from Arnebia euchroma and their related anti-HCV and antibacterial activities. AB - Three new hydroquinone terpenoids with benzogeijerene skeletons, euchroquinols A C (1- 3), and a new monoterpenylbenzenoid, 9,17-epoxyarnebinol (4), along with five known compounds were isolated from the stem bark of ARNEBIA EUCHROMA. Shikonin (6) exhibited potent anti-HCV activity with a selective index of 43.56, and compounds 1, 6, and des-O-methyllasiodiplodin (7) showed anti-Staphylococcus aureus activity with MICs of 0.5, 0.125, and 0.125 mg/mL, respectively. PMID- 21984334 TI - Dynamic intra-japonica subspecies variation and resource application. AB - We constructed a physical map of O. sativa ssp. japonica cv. ZH11 and compared it and its random sample sequences with the Nipponbare RefSeq derived from the same subspecies. This comparison showed that the two japonica genomes were highly syntenic but revealed substantial differences in terms of structural variations, rates of substitutions and indels, and transposable element content. For example, contractions/expansions as large as 450 kb and repeat sequences that were present in high copy numbers only in ZH11 were detected. In tri-alignment regions using the indica variety 93-11 sequence as an outgroup, we found that: (1) the substitution rates of the two japonica-indica inter-subspecies comparison combinations were close but almost a magnitude higher than the substitution rate between the japonica rice varieties ZH11 and Nipponbare; (2) of the substitutions found between ZH11 and Nipponbare, 47.2% occurred in ZH11 and 52.6% in Nipponbare; (3) of the indels found between ZH11 and Nipponbare, the indels that occurred in ZH11 were 15.8 times of those in Nipponbare. Of the indels that occurred in ZH11, 75.67% were insertions and 24.33% deletions. Of the indels that occurred in Nipponbare, 48.23% were insertions and 51.77% were deletions. The ZH11 comparative map covered four Nipponbare physical gaps, detected assembly errors in the Nipponbare sequence, and was integrated with the FSTs of a large ZH11 T-DNA insertion mutant library. ZH11 BAC clones can be browsed, searched, and obtained at our website, http://GResource.hzau.edu.cn. PMID- 21984342 TI - Use of Oncotype DX in Women with Node-Positive Breast Cancer. AB - Women with early stage breast cancer frequently receive adjuvant chemotherapy to prevent recurrence; however, not all patients benefit. Recently, gene expression marker panels, such as Oncotype DX, that may better predict risk of breast cancer recurrence have become commercially available and are being used to guide treatment decisions. Oncotype DX analyzes the expression of 21 genes within a tumor to determine a recurrence score that corresponds to a specific likelihood of breast cancer recurrence within 10 years of the initial diagnosis, as well as response to adjuvant treatment. We examined the published literature on the analytic validity, clinical validity, and clinical utility of Oncotype DX in guiding adjuvant treatment decisions in women with lymph node-positive breast cancer. PMID- 21984341 TI - Gossypin induces G2/M arrest in human malignant glioma U251 cells by the activation of Chk1/Cdc25C pathway. AB - Gossypin is a flavone that was originally isolated from Hibiscus vitifolius and has traditionally been used for the treatment of diabetes, jaundice, and inflammation. Recently, gossypin was found to have potent anticancer properties; however, its effect on human gliomas still remain unknown. To investigate the potential anticancer effects of gossypin on malignant gliomas and analyze the associated molecular mechanisms, we treated human glioma U251 cells with gossypin. Our study showed that the treatment of U251 cells with gossypin inhibited cell proliferation in a dose- and time-dependent manner and was observed to be minimally toxic to normal human astrocytes. Gossypin's effect on cell cycle distribution was observed, and we found that it induced G2/M-phase arrest in U251 cells. An analysis of cell-cycle regulatory proteins indicated that the arresting effect of gossypin on the cell cycle at G2/M phase was involved in the phosphorylation of cell division cycle 25C (Cdc25C) tyrosine phosphatase via the activation of checkpoint kinase 1 (Chk1). These findings indicate that gossypin is a potential treatment of gliomas because of gossypin's potential to regulate the proliferation of U251 cells via the cell-cycle regulatory proteins Chk1 and Cdc25C. PMID- 21984343 TI - Design of an integrated master-slave robotic system for minimally invasive surgery. AB - BACKGROUND: Minimally invasive surgery (MIS) robots are commonly used in hospitals and medical centres. However, currently available robotic systems are very complicated and huge, greatly raising system costs and the requirements of operating rooms. These disadvantages have become the major impediments to the expansion of MIS robots. METHODS: An integrated MIS robotic system is proposed based on the analysis of advantages and disadvantages of different MIS robots. In the proposed system, the master manipulators, slave manipulators, image display device and control system have been designed as a whole. Modular design is adopted for the control system for easy maintenance and upgrade. The kinematic relations between the master and the slave are also investigated and embedded in software to realize intuitive movements of hand and instrument. Finally, animal experiments were designed to test the effectiveness of the robot. RESULTS: The robot realizes natural hand-eye movements between the master and the slave to facilitate MIS operations. The experimental results show that the robot can realize similar functions to those of current commercialized robots. CONCLUSIONS: The integrated design simplifies the robotic system and facilitates use of the robot. Compared with the commercialized robots, the proposed MIS robot achieves similar functions and features but with a smaller size and less weight. PMID- 21984345 TI - Deterrence and transmission as mechanisms ensuring reliability of gossip. AB - Spreading information about the members of one's group is one of the most universal human behaviors. Thanks to gossip, individuals can acquire the information about their peers without sustaining the burden of costly interactions with cheaters, but they can also create and revise social bonds. Gossip has also several positive functions at the group level, promoting cohesion and norm compliance. However, gossip can be unreliable, and can be used to damage others' reputation or to circulate false information, thus becoming detrimental to people involved and useless for the group. In this work, we propose a theoretical model in which reliability of gossip depends on the joint functioning of two distinct mechanisms. Thanks to the first, i.e., deterrence, individuals tend to avoid informational cheating because they fear punishment and the disruption of social bonds. On the other hand, transmission provides humans with the opportunity of reducing the consequences of cheating through a manipulation of the source of gossip. PMID- 21984344 TI - Host cell processes to accomplish mechanical and non-circulative virus transmission. AB - Mechanical vector-less transmission of viruses, as well as vector-mediated non circulative virus transmission, where the virus attaches only to the exterior of the vector during the passage to a new host, are apparently simple processes: the viruses are carried along with the wind, the food or by the vector to a new host. We discuss here, using the examples of the non-circulatively transmitted Cauliflower mosaic virus that binds to its aphid vector's exterior mouthparts, and that of the mechanically (during feeding activity) transmitted Autographa californica multicapsid nucleopolyhedrovirus, that transmission of these viruses is not so simple as previously thought. Rather, these viruses prepare their transmission carefully and long before the actual acquisition event. Host-virus interactions play a pivotal and specialised role in the future encounter with the vector or the new host. This ensures optimal propagation and enlarges the tremendous bottleneck transmission presents for viruses and other pathogens. PMID- 21984347 TI - Regulation of bacterial communities through antimicrobial activity by the coral holobiont. AB - Interactions between corals and associated bacteria and amongst these bacterial groups are likely to play a key role in coral health. However, the complexity of these interactions is poorly understood. We investigated the functional role of specific coral-associated bacteria in maintaining microbial communities on the coral Acropora millepora (Ehrenberg 1834) and the ability of coral mucus to support or inhibit bacterial growth. Culture-independent techniques were used to assess bacterial community structures whilst bacterial culture was employed to assess intra- and inter-specific antimicrobial activities of bacteria. Members of Pseudoalteromonas and ribotypes closely related to Vibrio coralliilyticus displayed potent antimicrobial activity against a range of other cultured isolates and grew readily on detached coral mucus. Although such bacterial ribotypes would be expected to have a competitive advantage, they were rare or absent on intact and healthy coral colonies growing in situ (analysed using denaturing gradient gel electrophoresis and 16S rRNA gene sequencing). The most abundant bacterial ribotypes found on healthy corals were Gammaproteobacteria, previously defined as type A coral associates. Our results indicate that this group of bacteria and specific members of the Alphaproteobacteria described here as 'type B associates' may be important functional groups for coral health. We suggest that bacterial communities on coral are kept in check by a combination of host-derived and microbial interactions and that the type A associates in particular may play a key role in maintaining stability of microbial communities on healthy coral colonies. PMID- 21984346 TI - Ultrafast time-resolved spectroscopy of the light-harvesting complex 2 (LH2) from the photosynthetic bacterium Thermochromatium tepidum. AB - The light-harvesting complex 2 from the thermophilic purple bacterium Thermochromatium tepidum was purified and studied by steady-state absorption and fluorescence, sub-nanosecond-time-resolved fluorescence and femtosecond time resolved transient absorption spectroscopy. The measurements were performed at room temperature and at 10 K. The combination of both ultrafast and steady-state optical spectroscopy methods at ambient and cryogenic temperatures allowed the detailed study of carotenoid (Car)-to-bacteriochlorophyll (BChl) as well BChl-to BChl excitation energy transfer in the complex. The studies show that the dominant Cars rhodopin (N=11) and spirilloxanthin (N=13) do not play a significant role as supportive energy donors for BChl a. This is related with their photophysical properties regulated by long pi-electron conjugation. On the other hand, such properties favor some of the Cars, particularly spirilloxanthin (N=13) to play the role of the direct quencher of the excited singlet state of BChl. PMID- 21984348 TI - Genotypic characterization of phage-typed indigenous soybean bradyrhizobia and their host range symbiotic effectiveness. AB - Analysis of genetic diversity among indigenous rhizobia and its symbiotic effectiveness with soybean cultivar is important for development of knowledge about rhizobial ecology. In India, little is known about the genetic resources and diversity of rhizobia nodulating soybean. Indigenous bradyrhizobia isolated from root nodules of soybean plants, collected from traditional cultivating regions of two states (Madhya Pradesh and Uttar Pradesh) of India, were screened for bacteriophage sensitivity to identify successful broad host range symbiotic effectivity. Of 172 rhizobial isolates, 91 showed sensitivities to eight lytic phages and form ten groups on the basis of sensitivity patterns. The genetic diversity of 23 isolates belonging to different phage groups was assessed along with that of strains USDA123 and USDA94 by the restriction fragment length polymorphism (RFLP) analysis of 16S rDNA, intergenic spacer (IGS) (16S-23S rDNA), and DnaK regions. RFLP analysis of 16S rDNA formed 5 groups, whereas 19 and 9 groups were revealed by IGS and the DnaK genes, respectively. The IGS regions showed many amplified polymorphic bands. Nine isolates which revealed high RFLP polymorphism in the abovementioned regions (16S rRNA, IGS, DnaK) were used for 16S rRNA sequence analyses. The results indicate that taxonomically, all isolates were related to Rhizobium etli, Bradyrhizobium spp., and Bradyrhizobium yuanmingense. The doubling time of isolates varied from 9 h (MPSR155) to 16.2 h (MPSR068) in YM broth. Five isolates which did not show cross infectivity with isolated phage strains were studied for symbiotic efficiency. All isolates showed broad host range symbiotic effectiveness forming effective nodules on Vigna mungo, Vigna radiata, Vigna unguiculata, and Cajanus cajan. The present study provides information on genetic diversity and host range symbiosis of indigenous soybean rhizobia typed by different phages. PMID- 21984349 TI - Biliary stents in the millennium. AB - Biliary stents have now been in use for over two decades. Although a plethora of literature has been published on them, this review article is unique in its attempt to summarize important landmark trials and their implications on the management of various pancreatico-biliary disorders. This article will cover the various types of stents currently being used, established and upcoming indications, techniques of placement, and complications associated with stent use. PMID- 21984350 TI - Preparation of highly stable and water-dispersible silicon quantum dots by using an organic peroxide. PMID- 21984352 TI - Fractures of the shoulder girdle: editorial comment. PMID- 21984351 TI - Multilevel surgery improves gait in spastic hemiplegia but does not resolve hip dysplasia. AB - BACKGROUND: Multilevel orthopaedic surgery may improve gait in Type IV hemiplegia, but it is not known if proximal femoral osteotomy combined with adductor release as part of multilevel surgery in patients with hip dysplasia improves hip development. QUESTIONS/PURPOSES: We asked whether varus derotational osteotomy of the proximal femur, combined with adductor release, influenced hip development in patients with Type IV hemiplegia having multilevel surgery. PATIENTS AND METHODS: We retrospectively reviewed 11 children and adolescents with Type IV hemiplegia who had a proximal femoral osteotomy due to unilateral hip displacement to correct gait dysfunction between 1999 and 2006. The mean age at the time of surgery was 11.1 years (range, 7 to 16 years). We obtained the Movement Analysis Profile and Gait Profile Score before and after surgery. We also measured the Migration Percentage of Reimers and applied the Melbourne Cerebral Palsy Hip Classification System (MCPHCS). The minimum followup was 2 years 3 months (mean, 6 years 6 months; range, 2 years 3 months to 10 years 8 months). RESULTS: The majority of gait parameters improved but hip development was not normalized. According to the MCPHCS at last followup, no hips were classified as Grade I, two hips were classified as Grade II, and the remainder were Grade III and IV. CONCLUSIONS: Unilateral surgery including a proximal femoral osteotomy improved gait and walking ability in individuals with spastic hemiplegic cerebral palsy. However, hip dysplasia persists. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 21984353 TI - Does a modified gap-balancing technique result in medial-pivot knee kinematics in cruciate-retaining total knee arthroplasty? A pilot study. AB - BACKGROUND: Normal knee kinematics is characterized by posterior femorotibial rollback with tibial internal rotation and medial-pivot rotation in flexion. Cruciate-retaining TKAs (CR-TKAs) do not reproduce normal knee kinematics. QUESTIONS/PURPOSES: We hypothesized a more anatomic reconstruction of the medial femoral condyle, simultaneously preserving the tension of the PCL and medial collateral ligament, resulted in (1) medial-pivot rotation and tibial internal rotation, (2) lateral femoral rollback, and (3) reduced liftoff. PATIENTS AND METHODS: We compared 10 patients who underwent CR-TKA using the new technique at their 1-year followup to a matched control group of nine patients using a traditional gap-balancing technique at their 2- to 4-year followup. All patients received lateral radiographs in extension and flexion, which we utilized for three-dimensional implant matching to calculate tibial internal rotation, lateral rollback, and lateral liftoff in extension and flexion. RESULTS: The new gap balancing technique resulted in a median of 3.5 degrees tibial internal rotation with 2.7-mm rollback of the lateral femoral condyle relative to the medial condyle in flexion, which was different from the control group. We found no differences in liftoff between the groups. CONCLUSIONS: The new technique resulted in tibial internal rotation with flexion and lateral rollback comparing the lateral to the medial condyle in flexion, but no differences in condylar liftoff. These preliminary results were comparable to published kinematic results of an asymmetric CR-TKA or medial-pivot CR-TKA but not to symmetric CR-TKA. PMID- 21984354 TI - Pain relief and functional improvement remain 20 years after knee arthroplasty. AB - BACKGROUND: TKA provides demonstrable pain relief and improved health-related quality of life. Yet, a decline in physical function may occur over the long term despite the absence of implant-related problems. QUESTIONS/PURPOSES: (1) Does pain relief diminish over 20 years after TKA? (2) Does function decline over 20 years in terms of Knee Society function, knee, and walking scores? And (3) what is the patient-reported activity level at most recent followup? PATIENTS AND METHODS: We retrospectively identified 1471 patients with 1757 primary cruciate retaining TKAs implanted between 1975 and 1989 and identified 128 living patients (8.7%) with 171 TKAs. Ninety-three patients were women. We determined Knee Society scores prospectively and UCLA scores retrospectively. Minimum followup was 20 years (average, 21.1 years; range, 20-27 years). Average age at last followup was 82.3 years (range, 45-103 years). Of the 128 patients, 66 (73 TKAs) died after 20-year followup. RESULTS: Pain scores did not diminish over time (average, 49; range, 20-50). Average knee score was 78 (range, 39-97). Function, stair, and walking scores diminished over time. Average function score was 70 (range, 5-100), primarily due to an average stair score of 35 (range, 0-50); average walking score was 37 (range, 10-50). All but two patients (two TKAs) could negotiate stairs; 95 patients (124 TKAs) could walk at least five blocks; three patients (three TKAs) were housebound. Of the 62 patients still living (98 TKAs), the average UCLA activity score was 8.3 (range, 5-10). CONCLUSIONS: Although aging may cause a gradual decline in physical activity, an improved functional capacity and activity level continue 20 years or more after TKA. PMID- 21984355 TI - 50 years ago in CORR: recurrent dislocating patella: a long-term follow-up study James B. Jones, MD, Kenneth C. Francis, MD, John R. Mahoney, MD CORR 1961;20:230 240. PMID- 21984356 TI - Hydrogen exchange during cell-free incorporation of deuterated amino acids and an approach to its inhibition. AB - Perdeuteration, selective deuteration, and stereo array isotope labeling (SAIL) are valuable strategies for NMR studies of larger proteins and membrane proteins. To minimize scrambling of the label, it is best to use cell-free methods to prepare selectively labeled proteins. However, when proteins are prepared from deuterated amino acids by cell-free translation in H(2)O, exchange reactions can lead to contamination of (2)H sites by (1)H from the solvent. Examination of a sample of SAIL-chlorella ubiquitin prepared by Escherichia coli cell-free synthesis revealed that exchange had occurred at several residues (mainly at Gly, Ala, Asp, Asn, Glu, and Gln). We present results from a study aimed at identifying the exchanging sites and level of exchange and at testing a strategy for minimizing (1)H contamination during wheat germ cell-free translation of proteins produced from deuterated amino acids by adding known inhibitors of transaminases (1 mM aminooxyacetic acid) and glutamate synthetase (0.1 mM L: methionine sulfoximine). By using a wheat germ cell-free expression system, we produced [U-(2)H, (15)N]-chlorella ubiquitin without and with added inhibitors, and [U-(15)N]-chlorella ubiquitin as a reference to determine the extent of deuterium incorporation. We also prepared a sample of [U-(13)C, (15)N]-chlorella ubiquitin, for use in assigning the sites of exchange. The added inhibitors did not reduce the protein yield and were successful in blocking hydrogen exchange at C(alpha) sites, with the exception of Gly, and at C(beta) sites of Ala. We discovered, in addition, that partial exchange occurred with or without the inhibitors at certain side-chain methyl and methylene groups: Asn-H(beta), Asp H(beta), Gln-H(gamma), Glu-H(gamma), and Lys-H(epsilon). The side-chain labeling pattern, in particular the mixed chiral labeling resulting from partial exchange at certain sites, should be of interest in studies of large proteins, protein complexes, and membrane proteins. PMID- 21984357 TI - CO2 emission free co-generation of energy and ethylene in hydrocarbon SOFC reactors with a dehydrogenation anode. AB - A dehydrogenation anode is reported for hydrocarbon proton conducting solid oxide fuel cells (SOFCs). A Cu-Cr(2)O(3) nanocomposite is obtained from CuCrO(2) nanoparticles as an inexpensive, efficient, carbon deposition and sintering tolerant anode catalyst. A SOFC reactor is fabricated using a Cu-Cr(2)O(3) composite as a dehydrogenation anode and a doped barium cerate as a proton conducting electrolyte. The protonic membrane SOFC reactor can selectively convert ethane to valuable ethylene, and electricity is simultaneously generated in the electrochemical oxidative dehydrogenation process. While there are no CO(2) emissions, traces of CO are present in the anode exhaust when the SOFC reactor is operated at over 700 degrees C. A mechanism is proposed for ethane electro-catalytic dehydrogenation over the Cu-Cr(2)O(3) catalyst. The SOFC reactor also has good stability for co-generation of electricity and ethylene at 700 degrees C. PMID- 21984358 TI - Expected distance between terminal nucleotides of RNA secondary structures. AB - In "The ends of a large RNA molecule are necessarily close", Yoffe et al. (Nucleic Acids Res 39(1):292-299, 2011) used the programs RNAfold [resp. RNAsubopt] from Vienna RNA Package to calculate the distance between 5' and 3' ends of the minimum free energy secondary structure [resp. thermal equilibrium structures] of viral and random RNA sequences. Here, the 5'-3' distance is defined to be the length of the shortest path from 5' node to 3' node in the undirected graph, whose edge set consists of edges {i, i + 1} corresponding to covalent backbone bonds and of edges {i, j} corresponding to canonical base pairs. From repeated simulations and using a heuristic theoretical argument, Yoffe et al. conclude that the 5'-3' distance is less than a fixed constant, independent of RNA sequence length. In this paper, we provide a rigorous, mathematical framework to study the expected distance from 5' to 3' ends of an RNA sequence. We present recurrence relations that precisely define the expected distance from 5' to 3' ends of an RNA sequence, both for the Turner nearest neighbor energy model, as well as for a simple homopolymer model first defined by Stein and Waterman. We implement dynamic programming algorithms to compute (rather than approximate by repeated application of Vienna RNA Package) the expected distance between 5' and 3' ends of a given RNA sequence, with respect to the Turner energy model. Using methods of analytical combinatorics, that depend on complex analysis, we prove that the asymptotic expected 5'-3' distance of length n homopolymers is approximately equal to the constant 5.47211, while the asymptotic distance is 6.771096 if hairpins have a minimum of 3 unpaired bases and the probability that any two positions can form a base pair is 1/4. Finally, we analyze the 5'-3' distance for secondary structures from the STRAND database, and conclude that the 5'-3' distance is correlated with RNA sequence length. PMID- 21984359 TI - Transition probabilities for general birth-death processes with applications in ecology, genetics, and evolution. AB - A birth-death process is a continuous-time Markov chain that counts the number of particles in a system over time. In the general process with n current particles, a new particle is born with instantaneous rate lambda(n) and a particle dies with instantaneous rate MU(n). Currently no robust and efficient method exists to evaluate the finite-time transition probabilities in a general birth-death process with arbitrary birth and death rates. In this paper, we first revisit the theory of continued fractions to obtain expressions for the Laplace transforms of these transition probabilities and make explicit an important derivation connecting transition probabilities and continued fractions. We then develop an efficient algorithm for computing these probabilities that analyzes the error associated with approximations in the method. We demonstrate that this error controlled method agrees with known solutions and outperforms previous approaches to computing these probabilities. Finally, we apply our novel method to several important problems in ecology, evolution, and genetics. PMID- 21984360 TI - Transforming terpene-derived aldehydes into 1,2-epoxides via asymmetric alpha chlorination: subsequent epoxide opening with carbon nucleophiles. AB - Merging Jorgensen's and MacMillan's organocatalytic aldehyde chlorinations enables the synthesis of chiral vinylcyclopropanes and (-)-cis-aerangis lactone via terpene-derived 1,2-epoxides. PMID- 21984361 TI - Transcoronary ethanol ablation for recurrent ventricular tachycardia after failed catheter ablation: an update. AB - BACKGROUND: Despite substantial progress, radiofrequency catheter ablation (RFCA) fails in some patients. After encouraging results with transcoronary ethanol ablation (TCEA), we began offering TCEA routinely when endocardial and epicardial RFCA failed or a deep intramural substrate was likely. METHODS AND RESULTS: Among 274 consecutive patients who underwent 408 ventricular tachycardia (VT) ablation procedures, 27 patients (21 men; age, 63 +/- 13 years; left ventricular ejection fraction, 30 +/- 11%; ischemic cardiomyopathy, 14) had 29 TCEA procedures attempted. In 5 patients, TCEA was abandoned because of unfavorable anatomy. In 22 patients, a mean of 1.3 +/- 0.6 arteries (range, 1-3 arteries) were targeted for TCEA. After ablation, the targeted VT was no longer inducible in 18 of 22 (82%) patients. Complete heart block occurred in 5 patients, and 3 patients with advanced heart failure died within 30 days of the procedure. After the last TCEA procedure, a VT recurred in 64% of patients, and overall, 32% of patients died. Of 11 patients with prior VT storm, 9 were free of VT storm. At repeat study in 8 patients who had a recurrence, 7 had a new QRS morphology of VT originating from the same general substrate region as the prior VT. CONCLUSIONS: In patients with difficult-to-control VT in whom RFCA fails, TCEA prevents all VT recurrences in 36% and improves arrhythmia control in an additional 27%. Inadequate target vessels, collaterals, and recurrence of modified VTs limit efficacy, but TCEA continues to play an important role for difficult VTs in these high-risk patients. PMID- 21984362 TI - Forecasting hepatocellular carcinoma mortality in Taiwan using an age-period cohort model. AB - Hepatocellular carcinoma (HCC) is a common primary malignancy of the liver. Estimates of the future HCC burden are important for health planning. The authors applied an age-period-cohort (APC) model for a 15-year forecast of HCC mortality in Taiwan (based on mortality data between the years 1976 and 2005). It is found that for men, the mortality trend reverses itself in the period 2011-2015, from an increasing one to a slightly deceasing one. For women, the increasing trend reverses itself in the period 2001-2005. The age-adjusted HCC mortality for men and women in the most recent available years, 2006-2008, both fall in the range forecast by the APC model. Forecasting using the APC model can provide an advanced warning of trend reversals. PMID- 21984363 TI - Comparison of injuries experienced by international tourists visiting Australia and Australian residents. AB - This article compares the epidemiological profile of injury-related hospitalized morbidity of international tourists in New South Wales (NSW) with the hospitalized injury profile of NSW residents. Injury-related hospitalizations were identified from the NSW Admitted Patients Data Collection during 1 July 2000 to 30 June 2009. Injuries were identified using a principal diagnosis code of injury (ie, ICD-10-AM range S00-T98) and the presence of an external cause code (ie, ICD-10-AM range V00-Y98). Overseas tourists were more likely to be hospitalized for an injury following air and water transport, near-drowning, and pedestrian-related injuries. Sport or leisure-related activities were the most common activity conducted at the time of the incident. International tourists are at a higher risk of experiencing injuries particularly following recreational pursuits, while as a pedestrian, in vehicle crashes for older age groups, as a result of interpersonal violence for young males, and following a poisoning or cut/pierce injury for young females. Prevention measures should be undertaken to limit the incidence of injury among international tourists, particularly during active recreational activities and while using the roadways. PMID- 21984364 TI - Asthma and pregnancy: do they give clues to abnormal antiviral activity? PMID- 21984365 TI - Rhodium-catalyzed redox allylation reactions of ketones. AB - Ketones react with allyl acetate to generate tertiary homoallylic alcohols in the presence of a rhodium catalyst and bis(pinacolato)diboron. A range of substrates, including aryl, alkyl and cyclic ketones react smoothly under these conditions. Diastereoselective allylation reactions of functionalized ketones such as pregnenolone acetate are also reported. PMID- 21984367 TI - Haplosporidium nelsoni (MSX) in Japanese scallops Patinopecten yessoensis (Jay, 1857) from Dalian along the northern coast of the Yellow Sea, China. AB - The protozoan parasite Haplosporidium nelsoni (MSX) was identified in Japanese scallops Patinopecten yessoensis (Jay, 1857) from Dalian along the northern coast of the Yellow Sea, China by histopathologic examination, polymerase chain reaction (PCR) amplification, and in situ hybridization (ISH) assay. H. nelsoni plasmodia-like structures were identified in the digestive glands of scallops by histologic examination, but no parasite spores were observed. PCR using the Hap F2, R2 primer pair produced a sequence with 100% homology with the corresponding small subunit rDNA region of H. nelsoni. An ISH assay using the oligonucleotide probe MSX1347 produced a positive reaction with the Japanese scallop parasite. This is the first report of H. nelsoni in P. yessoensis in China. PMID- 21984368 TI - Effects of Metarhizium anisopliae conidia mixed with soil against the eggs of Aedes aegypti. AB - The effectiveness of Metarhizium anisopliae IP 46 conidia mixed with soil was tested against Aedes aegypti eggs. Mycelium and new conidia developed first on eggs between 4.8 and 15 days respectively after incubation of fungus-treated soils at 3.3 * 10(3) up to 3.3 * 10(5) conidia/g soil at 25 degrees C and relative humidities close to saturation. After 15-day incubation, 53.3% of the eggs exposed to soil with 3.3 * 10(5) conidia/g showed external development of mycelium and conidia. Fungus-inoculated soils (but not untreated controls) showed some mycelial growth and sporulation apart from the eggs. Some eggs on treated soils hatched; those larvae died and eventually showed fungal development on their bodies. The cumulative relative eclosion of larvae after submersion of treated eggs in water decreased from 52.2% at 3.3 * 10(3) conidia/g to 25.3% at 3.3 * 10(5) conidia/g. These findings clearly showed that A. aegypti eggs can be infected by M. anisopliae when deposited on fungus-contaminated soil. The effectiveness of M. anisopliae against gravid females, larvae, and also eggs of A. aegypti underscored the possible usefulness of this fungus as a mycoinsecticide, whether naturally occurring or artificially applied, in the breeding sites of this mosquito. PMID- 21984369 TI - Comparative efficacy of new commercial pediculicides against adults and eggs of Pediculus humanus capitis (head lice). AB - The use of pyrethroids to control head louse infestations have suffered considerable loss of efficacy due to the development of resistance. In the last past years, several new alternative products to synthetic pyrethroids have been developed and are sold in the Argentinean market against head lice. The present study investigated the efficacy of two new Argentinean products Nopucid Qubit(r) and Nopucid Bio Citrus(r) and its comparison with two reference products Nyda(r) and Hedrin(r). Nopucid Qubit(r) is a two-phase lotion containing geraniol and citronellol (phase 1) and ciclopentaxiloxane (phase 2); while Nopucid Bio Citrus(r) contains dimethicone, ciclopentaxiloxane, and bergamot essential oil. These products are physically acting compounds. The sensitivity of two laboratory assays for testing insecticide activity of new formulations was also compared. Mortality (100%) of motile forms occurred after they were exposed to any product for 1 and 2 min, either by in vitro or ex vivo test. Concerning ovicidal activity, the most effective pediculicides were Nopucid Bio Citrus(r) and Nyda(r), followed by Hedrin(r) and Nopucid Qubit(r). The present study revealed, for the first time, the efficacy of over-the-counter commercial pediculicides available in Argentine (Nopucid Bio Citrus(r) and Nopucid Qubit(r)) on either motile stages or eggs against head lice. PMID- 21984371 TI - The roots of evil: the amazing history of trichinellosis and Trichinella parasites. AB - This review aims to investigate, from a historical point of view, the roots of the Trichinella pathogens and the disease they produce, beginning from the times first recorded in the Bible and continuing until the scientific mysteries of the pathogen were finally unveiled. Our journey sheds light on "strange" epidemics developing before the discovery of the parasite and bearing a clinical similitude to trichinellosis; it follows the controversies that erupted after the nineteenth century discovery of the parasite and the subsequent official outbreaks, and then examines the pioneering methods used for its visualization. Finally, it tries to reveal the possible relationship of trichinellosis with the arts. Furthermore, it seems that the saga of the helminth, "destined to remain with us, both in nature and in the laboratory," will continue to haunt and fascinate scientists from both developing and developed countries, as they try to answer new questions about the parasite's "evil" nature. PMID- 21984370 TI - New insight into praziquantel against various developmental stages of schistosomes. AB - Praziquantel, due to high efficacy, excellent tolerability, few and transient side effects, simple administration, and competitive cost, is virtually the only drug of choice for treatment of human schistosomiasis. Treatment of schistosomiasis has shown great advances with the introduction of the drug into the therapeutic arsenal in areas that are endemic for the parasite. However, the drug presents various efficacies against different developmental stages of schistosomes, appearing an oddity intermitted mode. The present review article reviews the effects and mechanism of action of praziquantel against schistosomes briefly and suggests the research on this oddity phenomenon. PMID- 21984372 TI - CD24 promotes tumor cell invasion by suppressing tissue factor pathway inhibitor 2 (TFPI-2) in a c-Src-dependent fashion. AB - CD24 is a glycosyl-phosphatidylinositol-anchored protein with mucin-type structure that resides exclusively in membrane microdomains. CD24 is often highly expressed in carcinomas and correlates with poor prognosis. Experimentally, the over-expression or depletion of CD24 alters cell proliferation, adhesion, and invasion in vitro and tumor growth in vivo. However, little is known about the mechanisms by which CD24 mediates these cellular effects. Here we have studied the mechanism of CD24-dependent cell invasion using transient CD24 knock-down or over-expression in human cancer cell lines. We show that CD24 depletion reduced tumor cell invasion and up-regulated expression of Tissue Factor Pathway Inhibitor 2 (TFPI-2), a potent inhibitor of extracellular matrix degradation that can block metastases formation and tumor cell invasion. Over-expression of CD24 in A125 cells resulted in reduced TFPI-2 expression and enhanced invasion. We provide evidence that the activity of c-Src is reduced upon CD24 knock-down. The silencing of c-Src, similar to CD24, was able to enhance TFPI-2 expression and reduce tumor cell invasion. An inverse expression of CD24 and TFPI-2 was observed by immunohistochemical analysis of primary breast cancers (N = 1,174). TFPI-2 expression was highest in CD24 negative samples and lowered with increasing CD24 expression. Patients with a CD24 low/TFPI-2 high phenotype showed significantly better survival compared to CD24 high/TFPI-2 low patients. Our results provide evidence that CD24 can regulate cell invasion via TFPI-2 and suggests a role of c Src in this process. PMID- 21984373 TI - Notch1 regulates chemotaxis and proliferation by controlling the CC-chemokine receptors 5 and 9 in T cell acute lymphoblastic leukaemia. AB - Tumour cells often express deregulated profiles of chemokine receptors that regulate cancer cell migration and proliferation. Notch1 pathway activation is seen in T cell acute lymphoblastic leukaemia (T-ALL) due to the high frequency of Notch1 mutations affecting approximately 60% of patients, causing ligand independent signalling and/or prolonging Notch1 half-life. We have investigated the possible regulative role of Notch1 on the expression and function of chemokine receptors CCR5, CCR9 and CXCR4 that play a role in determining blast malignant properties and localization of extramedullary infiltrations in leukaemia. We inhibited the pathway through gamma-Secretase inhibitor and Notch1 RNA interference and analysed the effect on the expression and function of chemokine receptors. Our results indicate that gamma-Secretase inhibitor negatively regulates the transcription level of the CC chemokine receptors 5 and 9 in T-ALL cell lines and patients' primary leukaemia cells, leaving CXCR4 expression unaltered. The Notch pathway also controls CCR5- and CCR9-mediated biological effects, ie chemotaxis and proliferation. Furthermore, engaging CCR9 through CCL25 administration rescues proliferation inhibition associated with abrogation of Notch activity. Finally, through RNA interference we demonstrated that the oncogenic isoform in T-ALL, Notch1, plays a role in controlling CCR5 and CCR9 expression and functions. These findings suggest that Notch1, acting in concert with chemokine receptors pathways, may provide leukaemia cells with proliferative advantage and specific chemotactic abilities, therefore influencing tumour cell progression and localization. PMID- 21984374 TI - Tunable fluorescent pH sensor based on water-soluble perylene tetracarboxylic acid/Fe(3+). AB - A novel fluorescent pH sensor with tunable response range was designed based on highly fluorescent 3,4:9,10-perylene tetracarboxylic ammonium, which could coordinate the paramagnetic Fe(3+) ions to turn off its fluorescence and could also release Fe(3+) to turn on the fluorescence again at higher pH. The fluorescent pH sensor was tunable in the presence of different ligands in aqueous solution. PMID- 21984375 TI - Biophysical functionality in polysaccharides: from Lego-blocks to nano-particles. AB - The objective of the paper is to show the very important biophysical concepts that have been developed with polysaccharides. In particular, an attempt will be made to relate "a posteriori" the fundamental aspects, both experimental and theoretical, with some industrial applications of polysaccharide-based materials. The overview of chain conformational aspects includes relationships between topological features and local dynamics, exemplified for some naturally occurring carbohydrate polymers. Thus, by using simulation techniques and computational studies, the physicochemical properties of aqueous solutions of polysaccharides are interpreted. The relevance of conformational disorder-order transitions, chain aggregation, and phase separation to the underlying role of the ionic contribution to these processes is discussed. We stress the importance of combining information from analysis of experimental data with that from statistical-thermodynamic models for understanding the conformation, size, and functional stability of industrially important polysaccharides. The peculiar properties of polysaccharides in industrial applications are summarized for the particularly important example of nanoparticles production, a field of growing relevance and scientific interest. PMID- 21984376 TI - Erythrocyte glutathione transferase: a potential new biomarker in chronic kidney diseases which correlates with plasma homocysteine. AB - The erythrocyte glutathione S-transferase (e-GST) is a member of a superfamily of inducible enzymes involved in cell detoxification that shows an increased expression in chronic kidney disease (CKD) patients. We propose a new automated analysis procedure for e-GST activity that has been validated in 72 CKD patients and 62 maintenance hemodialysis patients (MHD). Regression analysis was carried out to assess association between e-GST activity data, main clinical variables, and plasma homocysteine (Hcy), a modified sulfur amino acid known as potential risk factor for cardiovascular disease that is increased above normal levels in more than 90% of the uremic patients. An increased e-GST activity was confirmed in MHD patients (N=62; 10.2+/-0.4 U/gHb) compared with healthy subjects (N=80; 5.8+/-0.4 U/gHb), and as an original finding, a significant increase of e-GST activity was observed in pre-dialysis CKD patients with a positive correlation with disease severity weighted according to the four stages of "Kidney Disease Outcomes Quality Initiative" classification (7.4+/-0.5, 8+/-1, 9.5+/-0.6, 12+/-1 U/gHb, respectively). No correlation was found between e-GST activity and hemoglobin, transferrin, blood iron and the markers of systemic inflammation and renal function such as alpha-1 acid glycoprotein and high-sensitive C-Reactive Protein, beta-2 microglobulin and the index of malnutrition-inflammation PINI, while a significant correlation was observed for the first time between plasma Hcy and e-GST activity (r2=0.64, P<0.0001) in MHD patients. Hcy, however, was not identified as an inhibitor of e-GST enzyme. The results in this study suggest the potential for automated e-GST analysis as a valuable tool to further explore phase II-related uremic toxicity in CKD and MHD patients. PMID- 21984377 TI - Insulin resistance and the metabolism of branched-chain amino acids in humans. AB - Peripheral resistance to insulin action is the major mechanism causing the metabolic syndrome and eventually type 2 diabetes mellitus. The metabolic derangement associated with insulin resistance is extensive and not restricted to carbohydrates. The branched-chain amino acids (BCAAs) are particularly responsive to the inhibitory insulin action on amino acid release by skeletal muscle and their metabolism is profoundly altered in conditions featuring insulin resistance, insulin deficiency, or both. Obesity, the metabolic syndrome and diabetes mellitus display a gradual increase in the plasma concentration of BCAAs, from the obesity-related low-grade insulin-resistant state to the severe deficiency of insulin action in diabetes ketoacidosis. Obesity-associated hyperinsulinemia succeeds in maintaining near-normal or slightly elevated plasma concentration of BCAAs, despite the insulin-resistant state. The low circulating levels of insulin and/or the deeper insulin resistance occurring in diabetes mellitus are associated with more marked elevation in the plasma concentration of BCAAs. In diabetes ketoacidosis, the increase in plasma BCAAs is striking, returning to normal when adequate metabolic control is achieved. The metabolism of BCAAs is also disturbed in other situations typically featuring insulin resistance, including kidney and liver dysfunction. However, notwithstanding the insulin-resistant state, the plasma level of BCAAs in these conditions is lower than in healthy subjects, suggesting that these organs are involved in maintaining BCAAs blood concentration. The pathogenesis of the decreased BCAAs plasma level in kidney and liver dysfunction is unclear, but a decreased afflux of these amino acids into the blood stream has been observed. PMID- 21984378 TI - Nitric oxide regulates tissue transglutaminase localization and function in the vasculature. AB - The multifunctional enzyme tissue transglutaminase (TG2) contributes to the development and progression of several cardiovascular diseases. Extracellular rather than intracellular TG2 is enzymatically active, however, the mechanism by which it is exported out of the cell remains unknown. Nitric oxide (NO) is shown to constrain TG2 externalization in endothelial and fibroblast cells. Here, we examined the role of both exogenous and endogenous (endothelial cell-derived) NO in regulating TG2 localization in vascular cells and tissue. NO synthase inhibition in endothelial cells (ECs) using N-nitro L-arginine methyl ester (L NAME) led to a time-dependent decrease in S-nitrosation and increase in externalization of TG2. Laminar shear stress led to decreased extracellular TG2 in ECs. S-nitrosoglutathione treatment led to decreased activity and externalization of TG2 in human aortic smooth muscle and fibroblast (IMR90) cells. Co-culture of these cells with ECs resulted in increased S-nitrosation and decreased externalization and activity of TG2, which was reversed by L-NAME. Aged Fischer 344 rats had higher tissue scaffold-associated TG2 compared to young. NO regulates intracellular versus extracellular TG2 localization in vascular cells and tissue, likely via S-nitrosation. This in part, explains increased TG2 externalization and activity in aging aorta. PMID- 21984379 TI - Transglutaminase 6: a protein associated with central nervous system development and motor function. AB - Transglutaminases (TG) form a family of enzymes that catalyse various post translational modifications of glutamine residues in proteins and peptides including intra- and intermolecular isopeptide bond formation, esterification and deamidation. We have characterized a novel member of the mammalian TG family, TG6, which is expressed in a human carcinoma cell line with neuronal characteristics and in mouse brain. Besides full-length protein, alternative splicing results in a short variant lacking the second beta-barrel domain in man and a variant with truncated beta-sandwich domain in mouse. Biochemical data show that TG6 is allosterically regulated by Ca(2+) and guanine nucleotides. Molecular modelling indicates that TG6 could have Ca(2+) and GDP-binding sites related to those of TG3 and TG2, respectively. Localization of mRNA and protein in the mouse identified abundant expression of TG6 in the central nervous system. Analysis of its temporal and spatial pattern of induction in mouse development indicates an association with neurogenesis. Neuronal expression of TG6 was confirmed by double labelling of mouse forebrain cells with cell type-specific markers. Induction of differentiation in mouse Neuro 2a cells with NGF or dibutyryl cAMP is associated with an upregulation of TG6 expression. Familial ataxia has recently been linked to mutations in the TGM6 gene. Autoantibodies to TG6 were identified in immune mediated ataxia in patients with gluten sensitivity. These findings suggest a critical role for TG6 in cortical and cerebellar neurons. PMID- 21984380 TI - In vivo targeting of HER2-positive tumor using 2-helix affibody molecules. AB - Molecular imaging of human epidermal growth factor receptor type 2 (HER2) expression has drawn significant attention because of the unique role of the HER2 gene in diagnosis, therapy and prognosis of human breast cancer. In our previous research, a novel cyclic 2-helix small protein, MUT-DS, was discovered as an anti HER2 Affibody analog with high affinity through rational protein design and engineering. MUT-DS was then evaluated for positron emission tomography (PET) of HER2-positive tumor by labeling with two radionuclides, 68Ga and 18F, with relatively short half-life (t1/2<2 h). In order to fully study the in vivo behavior of 2-helix small protein and demonstrate that it could be a robust platform for labeling with a variety of radionuclides for different applications, in this study, MUT-DS was further radiolabeled with 64Cu or 111In and evaluated for in vivo targeting of HER2-positive tumor in mice. Design 1,4,7,10 tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) conjugated MUT-DS (DOTA MUT-DS) was chemically synthesized using solid phase peptide synthesizer and I2 oxidation. DOTA-MUT-DS was then radiolabeled with 64Cu or 111In to prepare the HER2 imaging probe (64Cu/111In-DOTA-MUT-DS). Both biodistribution and microPET imaging of the probe were evaluated in nude mice bearing subcutaneous HER2 positive SKOV3 tumors. DOTA-MUT-DS could be successfully synthesized and radiolabeled with 64Cu or 111In. Biodistribution study showed that tumor uptake value of 64Cu or 111In-labeled DOTA-MUT-DS was 4.66+/-0.38 or 2.17+/-0.15%ID/g, respectively, in nude mice bearing SKOV3 xenografts (n=3) at 1 h post-injection (p.i.). Tumor-to-blood and tumor-to-muscle ratios for 64Cu-DOTA-MUT-DS were attained to be 3.05 and 3.48 at 1 h p.i., respectively, while for 111In-DOTA-MUT DS, they were 2.04 and 3.19, respectively. Co-injection of the cold Affibody molecule ZHER2:342 with 64Cu-DOTA-MUT-DS specifically reduced the SKOV3 tumor uptake of the probe by 48%. 111In-DOTA-MUT-DS displayed lower liver uptake at all the time points investigated and higher tumor to blood ratios at 4 and 20 h p.i., when compared with 64Cu-DOTA-MUT-DS. This study demonstrates that the 2-helix protein based probes, 64Cu/111In DOTA-MUT-DS, are promising molecular probes for imaging HER2-positive tumor. Two-helix small protein scaffold holds great promise as a novel and robust platform for imaging and therapy applications. PMID- 21984382 TI - Study of the urinary and faecal excretion of Nepsilon-carboxymethyllysine in young human volunteers. AB - The dietary habits of the adolescent population with a high intake of snack and fast foods mean that they consume a high rate of which in turn leads to the development of different degenerative disorders. There are few studies available on MRP absorption and metabolism. We investigated the effects of a MRP-high and a MRP-low diet on carboxymethyllysine (CML) intake and excretion in 11-14 years adolescent males. In a 2-period crossover trial, 20 healthy subjects were randomly assigned to two groups. The first group consumed the MRP-low diet for 2 weeks, observed a 40-day washout period, and then consumed the MRP-high diet for 2 weeks. The second group received the diets in the reverse order. Subjects collected urine and faeces on the last 3 days of each dietary period. The consumption of the MRP-high diet led to a higher CML input (P < 0.05) (11.28 vs. 5.36 mg/day CML for MRP-high and -low diet, respectively). In parallel, the faecal excretion was also greater (P < 0.05) (3.52 vs. 1.23 mg/day CML, respectively) and proportional to the dietary intake. The urinary elimination of CML was not increased significantly when the MRP-high diet was consumed compared to consumption of the MRP-low diet, and was not proportional to the dietary exposure of CML. In conclusion it was shown that CML absorption and faecal excretion were highly influenced by dietary CML levels. Since the compound has long-term effects on health, an excessive intake deserves attention, especially in a population nutritionally at risk as adolescents. PMID- 21984381 TI - Efficacy and toxicity of the antimicrobial peptide M33 produced with different counter-ions. AB - The tetra-branched peptide M33 (Pini et al. in FASEB J 24:1015-1022, 2010) is under evaluation in animal models for its activity as antimicrobial agent in lung infections and sepsis. The preclinical development of a new drug requires medium scale manufacture for tests of efficacy, biodistribution, pharmacokinetics and toxicity. In order to produce the most suitable peptide form for these purposes, we evaluated the behaviour of the peptide M33 obtained with different counter ions. We compared activity and toxicity in vitro and in vivo of the peptide M33 produced as trifluoroacetate salt (TFacetate) and as acetate salt. The two forms did not differ substantially in terms of efficacy in vitro or in vivo but showed different toxicities for human cells and in animals. M33-TFacetate proved to be 5 30% more toxic than M33-acetate for cells derived from normal bronchi and cells carrying DeltaF508 mutation in the CFTR gene, the most frequent variant in cystic fibrosis. M33-TFacetate produced manifest signs of in vivo toxicity immediately after administration, whereas M33-acetate only generated mild signs, which disappeared within a few hours. The peptide M33-acetate proved more suitable for the development of a new drug, and was therefore chosen for further characterization. PMID- 21984383 TI - A miniemulsion polymerization technique for encapsulation of silicon quantum dots in polymer nanoparticles. AB - Miniemulsion polymerization techniques were used to encapsulate luminescent alkylated silicon quantum dots (Si-QDs) within polymer nanoparticles composed of styrene and 4-vinylbenzaldehyde monomers. The polymer nanoparticles had mean diameters in the range 90-150 nm depending on the reaction conditions, however all samples showed narrow particle size distributions, as determined by dynamic light scattering and atomic force microscopy. The Si-QDs were found to have a small, but beneficial effect on the polymerization process by reducing the polydispersity of the final polymer particles, which we attribute to co surfactant action of the undecene used to form the alkyl capping layer on the Si QDs. Confocal microspectroscopy was used to confirm that the luminescent alkylated Si-QDs were encapsulated within the polymer nanoparticles and also provided luminescence and Raman spectra which show peaks corresponding to both alkylated Si-QDs and the polymer nanoparticles. Treatment of the polymer nanoparticles with dilute aqueous sodium hydroxide solution, which is known to corrode Si and extinguish the luminescence of alkylated Si-QDs, results in only a partial reduction in luminescence suggesting that the majority of the alkylated Si-QDs are encapsulated sufficiently deep within the polymer matrix to protect them from alkaline attack. Miniemulsion polymerization of the monomers styrene and 4-vinylbenzaldehyde affords polymer nanoparticles displaying reactive aldehyde groups upon their surfaces, which could then be decorated with a selection of molecules through imine, oxime or hydrazone condensation reactions. We speculate that polymer-SiQD composite nanoparticles whose surfaces can be further decorated will increase the utility of luminescent Si-QDs in applications such as anti-counterfeiting and as probes of biological processes. PMID- 21984384 TI - The effect of different ethoxylations for sorbitan monolaurate on enhancing simultaneous saccharification and fermentation (SSF) of wheat straw to ethanol. AB - In this paper, four nonionic surfactants with different hydrophilic-lipophilic balance (HLB) based on sorbitan monolaurate were synthesized by introducing ethylene oxide gas (n = 20, 40, 60, and 80 ethylene oxide units). The chemical structure of the prepared ethoxylated surfactants was confirmed using Fourier transform-infrared and (1)H NMR spectroscopes. The surface tension and thermodynamic properties of the prepared surfactants have been studied. The simultaneous saccharification and fermentation (SSF) process for ethanol production from microwave/alkali pretreated wheat straw has been assayed using nonionic surfactants have different ethylene oxide units. Ethanol yield was 82% and 61% for Kluyveromyces marxianus and Saccharomyces cerevisiae, respectively, with the addition of 2.5 g/l of the prepared nonionic surfactant (HLB = 18.2). Results show that the production of ethanol from microwave/alkali pretreated wheat straw increased with increasing the (HLB) value of the nonionic surfactant. PMID- 21984385 TI - A simple colorimetric enzymatic-assay for okadaic acid detection based on the immobilization of protein phosphatase 2A in sol-gel. AB - Okadaic acid (OA), a lipophilic toxin, is produced by Dinophysis and Prorocentrum, and causes diarrheic shellfish poisoning to humans. The mechanism of OA action is based on the reversible inhibition of protein phosphatase type 2A (PP2A) by the toxin. Therefore, this inhibition could be used to develop assay for OA detection. In this work, a colorimetric test based on the PP2A inhibition was developed for OA detection. PP2A from GTP and Millipore was immobilized on silica sol-gel, and the detection was performed. A limit of detection of 0.29 and 1.14 MUg/L was respectively observed for enzyme from GTP and Millipore. The immobilization technique provided a tool to preserve the enzymatic activity, which is very unstable in solution. The PP2A immobilized sol-gel exhibited a storage stability of near 5 months, when microtiter plate with enzyme-immobilized polymer was kept at -18C degrees . The combination of the simplicity of the colorimetric method, along with long storage stability achieved by sol-gel immobilization, demonstrated the potentiality of this technique to be used for commercial purpose. PMID- 21984386 TI - N-acetylgalactosamine kinase: a naturally promiscuous small molecule kinase. AB - N-acetylgalactosamine kinase is a member of the GHMP family of small molecule kinases which catalyses the ATP-dependent phosphorylation of N acetylgalactosamine. It is highly similar in structure and sequence to galactokinase. Alteration of galactokinase at a key tyrosine residue (Tyr-379 in the human enzyme) has been shown to dramatically enhance the substrate range of this enzyme. Here, we investigated the substrate specificity of the wild type N acetylgalactosamine kinase and demonstrated that it can also catalyse the phosphorylation of N-acetylglucosamine and N-acetylmannosamine. In human N acetylgalactosamine kinase, the equivalent residue to Tyr-379 in galactokinase is Phe-444. Alteration of this residue did not result in dramatic changes to the specificity of the enzyme. The more relaxed substrate specificity of N acetylgalactosamine kinase, compared to galactokinase, can be explained by the greater flexibility of a glycine rich loop in the active site of the enzyme. These results suggest that N-acetylgalactosamine kinase is a potential biocatalyst for the phosphorylation of N-acetyl sugars. However, it is unlikely that it will be possible to further broaden the substrate range by alteration of Phe-444. PMID- 21984387 TI - Interest in participating in smoking cessation treatment among Latino primary care patients. AB - Smoking is the leading preventable cause of disease and death for U.S. Latinos. This study identified correlates of interest in participating in a smoking cessation program among urban Latinos seen in community clinics. Interviews were completed with 141 current smokers. Participants were predominantly Spanish speaking (93%) males (66%), who were on average 37.6 years old and smoked 8.7 cigarettes per day. Over two-thirds (63%) of participants were "definitely interested" in participating in a smoking cessation program. Participants who smoked more cigarettes per day and reported greater nicotine dependence, depression, and readiness to quit were more likely to be interested, while those employed fulltime were less likely to report high interest. Treatment preferences were consistent with Clinical Practice Guidelines recommending counseling, social support, and pharmacotherapy. Results support recommendations that healthcare providers intervene with all Latino smokers, including light smokers and those who do not report initial interest in smoking cessation. PMID- 21984388 TI - Cytochrome c6-like protein as a putative donor of electrons to photosystem I in the cyanobacterium Nostoc sp. PCC 7119. AB - Most organisms performing oxygenic photosynthesis contain either cytochrome c(6) or plastocyanin, or both, to transfer electrons from cytochrome b(6)-f to photosystem I. Even though plastocyanin has superseded cytochrome c(6) along evolution, plants contain a modified cytochrome c(6), the so called cytochrome c(6A), whose function still remains unknown. In this article, we describe a second cytochrome c(6) (the so called cytochrome c(6)-like protein), which is found in some cyanobacteria but is phylogenetically more related to plant cytochrome c(6A) than to cyanobacterial cytochrome c(6). In this article, we conclude that the cytochrome c(6)-like protein is a putative electron donor to photosystem I, but does play a role different to that of cytochrome c(6) and plastocyanin as it cannot accept electrons from cytochrome f. The existence of this third electron donor to PSI could explain why some cyanobacteria are able to grow photoautotrophically in the absence of both cytochrome c(6) and plastocyanin. In any way, the Cyt c(6)-like protein from Nostoc sp. PCC 7119 would be potentially utilized for the biohydrogen production, using cell-free photosystem I catalytic nanoparticles. PMID- 21984390 TI - Multifunctional composite core-shell nanoparticles. AB - In this review paper, the state-of-the-art knowledge of the core-shell multifunctional nanoparticles (MNPs), especially with unique physiochemical properties, is presented. The synthesis methods were summarized from the aspects of both the advantages and the demerits. The core includes the inexpensive and easily oxidized metals and the noble shells include the relatively noble metals, carbon, silica, other oxides, and polymers. The properties including magnetic, optical, anti-corrosion and the surface chemistry of the NPs are thoroughly reviewed. The current status of the applications is reviewed with the detailed examples including the catalysis, giant magnetoresistance (GMR) sensing, electromagnetic interface shielding or microwave absorption, biomedical drug delivery, and the environmental remediation. PMID- 21984389 TI - [Colposcopy in the diagnosis of early cervical cancer]. AB - Cervical intraepithelial neoplasia and early cervical cancer are characterized by colposcopic minor and major changes and vessel abnormalities. In minor changes check-ups in most cases are sufficient. To avoid R1-resection and conization associated premature birth, conization should be performed under colposcopic visualization. In the USA and UK evidence based colposcopic guidelines were issued based on cytologic and colposcopic classifications. The German Society of Colposcopy (AG-CPC) published recommendations for the daily practice for all findings. For screening purposes there is no evidence to recommend colposcopy. In these cases, cytology is at the forefront, whereas colposcopy is only indicated in cases of conspicuous or unclear cytological results. PMID- 21984391 TI - One-step method for plasma determination of ibuprofen by chemiluminescence coupled ultrafiltration and application in a pharmacokinetic study. AB - A simple one-step method is established for plasma determination of ibuprofen and its pharmacokinetic study. The method involves simple sample pre-treatment by dilution, rapid separation by ultrafiltration (UF) and online sensitive detection by chemiluminescence (CL) based on significant intensity enhancement of ibuprofen on the weak CL of potassium permanganate and sodium sulphite in an acidic system. The calibration curve for ibuprofen is linear in the range 0.1-50.0 ug/mL in rat plasma. Average recoveries of ibuprofen at 0.80, 12.0 and 40.0 ug/mL amounted to 98.0 +/- 4.2%, 101.2 +/- 3.6% and 99.3 +/- 5.4%, respectively. Standard deviations of intra- and inter-day measurement precision and accuracy are within +/-10.0%. The detection limit for ibuprofen is 10.0 ug/L in plasma samples. Pharmacokinetic study of ibuprofen by the validated method shows that the mean plasma drug concentration-time course confirms to a classical two-compartment open model with first-order absorption. The proposed method will be an alternative for pre-clinical pharmacokinetic study of ibuprofen and other non steroidal anti-inflammatory drugs. PMID- 21984392 TI - Dynamic changes in the microbial community composition in microbial fuel cells fed with sucrose. AB - The performance and dynamics of the bacterial communities in the biofilm and suspended culture in the anode chamber of sucrose-fed microbial fuel cells (MFCs) were studied by using denaturing gradient gel electrophoresis (DGGE) of PCR amplified partial 16S rRNA genes followed by species identification by sequencing. The power density of MFCs was correlated to the relative proportions of species obtained from DGGE analysis in order to detect bacterial species or taxonomic classes with important functional role in electricity production. Although replicate MFCs showed similarity in performance, cluster analysis of DGGE profiles revealed differences in the evolution of bacterial communities between replicate MFCs. No correlation was found between the proportion trends of specific species and the enhancement of power output. However, in all MFCs, putative exoelectrogenic denitrifiers and sulphate-reducers accounted for approximately 24% of the bacterial biofilm community at the end of the study. Pareto-Lorenz evenness distribution curves extracted from the DGGE patterns obtained from time course samples indicated community structures where shifts between functionally similar species occur, as observed within the predominant fermentative bacteria. These results suggest the presence of functional redundancy within the anodic communities, a probable indication that stable MFC performance can be maintained in changing environmental conditions. The capability of bacteria to adapt to electricity generation might be present among a wide range of bacteria. PMID- 21984393 TI - Ligand-independent transforming growth factor-beta type I receptor signalling mediates type I collagen-induced epithelial-mesenchymal transition. AB - Evidence suggests epithelial-mesenchymal transition (EMT) as one potential source of fibroblasts in idiopathic pulmonary fibrosis. To assess the contribution of alveolar epithelial cell (AEC) EMT to fibroblast accumulation in vivo following lung injury and the influence of extracellular matrix on AEC phenotype in vitro, Nkx2.1-Cre;mT/mG mice were generated in which AECs permanently express green fluorescent protein (GFP). On days 17-21 following intratracheal bleomycin administration, ~4% of GFP-positive epithelial-derived cells expressed vimentin or alpha-smooth muscle actin (alpha-SMA). Primary AECs from Nkx2.1-Cre;mT/mG mice cultured on laminin-5 or fibronectin maintained an epithelial phenotype. In contrast, on type I collagen, cells of epithelial origin displayed nuclear localization of Smad3, acquired spindle-shaped morphology, expressed alpha-SMA and phospho-Smad3, consistent with activation of the transforming growth factor beta (TGFbeta) signalling pathway and EMT. alpha-SMA induction and Smad3 nuclear localization were blocked by the TGFbeta type I receptor (TbetaRI, otherwise known as Alk5) inhibitor SB431542, while AEC derived from Nkx2.1 Cre;Alk5(flox/KO) mice did not undergo EMT on collagen, consistent with a requirement for signalling via Alk5 in collagen-induced EMT. Inability of a pan specific TGFbeta neutralizing antibody to inhibit effects of collagen together with absence of active TGFbeta in culture supernatants is consistent with TGFbeta ligand-independent activation of Smad signalling. These results support the notion that AECs can acquire a mesenchymal phenotype following injury in vivo and implicate type I collagen as a key regulator of EMT in AECs through signalling via Alk5, likely in a TGFbeta ligand-independent manner. PMID- 21984396 TI - Nocardia scleritis-clinical presentation and management: a report of three cases and review of literature. AB - AIM: This study aims to describe the clinical features and management of Nocardia scleritis. METHODS: The authors retrospectively reviewed medical charts of three patients with microbiologically proven Nocardia scleritis and reviewed literature. RESULTS: All the patients presented with areas of well-demarcated, circumscribed abscess. No specific clinical feature could be attributed to the causative organism. Nocardia was identified by smear and culture from the scleral exudates. The medical management was based on the antibiotic sensitivity. Surgical exploration of the suppurated area along with the healthy margins was done on all patients. Two patients required multiple explorations. All three patients resolved with a good visual and tectonic outcome. The literature review also suggests a good outcome with prolonged medical management though the preferred antibiotic has changed over the years. CONCLUSION: Though the prevalence of a disease like Nocardia scleritis is low, the results suggest that specific diagnosis and appropriate management can lead to a good outcome. PMID- 21984395 TI - Phosphorylated pVEGFR2/KDR receptor expression in uveal melanomas: relation with HIF2alpha and survival. AB - Hypoxia and its down-stream activated pathways are commonly involved in tumor progression. Genes involved in angiogenesis and glycolysis, i.e. vascular endothelial growth factor (VEGF) and lactase dehydrogenase A (LDHA), respectively, are transcriptionally controlled by the hypoxia inducible factors 1alpha and 2alpha (HIF1alpha and HIF2alpha). A series of 60 uveal melanomas were immunohistochemically assessed for the expression of VEGF and the phosphorylated/activated form of VEGF receptor 2 (pVEGFR2/KDR), after binding to VEGF. The expression of HIF1alpha, HIF2alpha and LDH5 was also investigated. Uveal melanomas overexpressing HIF2alpha (but not that of HIF1alpha) were significantly associated with high VEGF (P = 0.005), pVEGFR2/KDR (P < 0.0001) and LDH5 (P <= 0.0001). High LDH5 was linked with tumor necrosis (P = 0.01) and increased tumor size (P = 0.03). High VEGF was linked with phosphorylated pVEGFR2/KDR receptors. In univariate analysis high pVEGFR2/KDR receptor expression was significantly related with poor prognosis (P = 0.02). It is concluded that HIF2alpha plays an important role in the progression of uveal melanomas possibly by promoting the autocrine loop VEGF-pVEGFR2/KDR, and by enhancing the expression of LDHA gene, conferring thus a growth advantage. As pVEGFR2/KDR expression was significantly related with poor prognosis, inhibitors of this receptor may improve the clinical outcome of patients with pVEGFR2/KDR overexpressing uveal melanomas. PMID- 21984397 TI - Plasma cortisol concentrations and perceived anxiety in response to on-sight rock climbing. AB - Previous research suggested plasma cortisol concentrations in response to rock climbing have a cubic relationship with state anxiety and self-confidence. This research, however, was conducted in a situation where the climbers had previously climbed the route. The purpose of our study was to examine this relationship in response to on-sight climbing. Nineteen (13 male, 6 female) intermediate climbers volunteered to attend anthropometric and baseline testing sessions, prior to an on-sight ascent (lead climb or top-rope) of the test climb (grade 19 Ewbank/6a sport/5.10b YDS). Data recorded included state anxiety, self-confidence and cortisol concentrations prior to completing the climb. Results indicated that there were no significant differences in state anxiety, self-confidence and plasma cortisol concentration regardless of the style of ascent (lead climb or top-rope) in an on-sight sport climbing context. Regression analysis indicated there was a significant linear relationship between plasma cortisol concentrations and self-confidence (r= - 0.52, R2=0.267, p=0.024), cognitive (r=0.5, R2=0.253, p=0.028), and somatic anxieties (r=0.46, R2=0.210, p=0.049). In an on-sight condition the relationships between plasma cortisol concentrations with anxiety (cognitive and somatic) and self-confidence were linear. PMID- 21984394 TI - Facioscapulohumeral muscular dystrophy (FSHD): an enigma unravelled? AB - Facioscapulohumeral muscular dystrophy (FSHD) is the third most common muscular dystrophy after the dystrophinopathies and myotonic dystrophy and is associated with a typical pattern of muscle weakness. Most patients with FSHD carry a large deletion in the polymorphic D4Z4 macrosatellite repeat array at 4q35 and present with 1-10 repeats whereas non-affected individuals possess 11-150 repeats. An almost identical repeat array is present at 10q26 and the high sequence identity between these two arrays can cause difficulties in molecular diagnosis. Each 3.3 kb D4Z4 unit contains a DUX4 (double homeobox 4) gene that, among others, is activated upon contraction of the 4q35 repeat array due to the induction of chromatin remodelling of the 4qter region. A number of 4q subtelomeric sequence variants are now recognised, although FSHD only occurs in association with three 'permissive' haplotypes, each of which is associated with a polyadenylation signal located immediately distal of the last D4Z4 unit. The resulting poly-A tail appears to stabilise DUX4 mRNAs transcribed from this most distal D4Z4 unit in FSHD muscle cells. Synthesis of both the DUX4 transcripts and protein in FSHD muscle cells induces significant cell toxicity. DUX4 is a transcription factor that may target several genes which results in a deregulation cascade which inhibits myogenesis, sensitises cells to oxidative stress and induces muscle atrophy, thus recapitulating many of the key molecular features of FSHD. PMID- 21984398 TI - Peak BMD assessment in a Chinese infantry recruit group. AB - Peak bone mass is an important factor influencing the occurrence of osteoporosis and osteoporotic fracture in adulthood. We measured the areal bone mineral density (BMD) in a Chinese male infantry recruit group ranging in age from 17 to 23 years and subsequently assessed peak BMD at the lumbar vertebrae and hip. This study included 812 Chinese men of Han ethnicity from 11 provinces and municipalities of China. The BMD, bone mineral content and the bone area of the lumbar vertebrae (L1-4), left femoral neck and total hip were measured using dual energy X-ray absorptiometry. Height, weight, waist and hip circumference were also measured at the same time. BMD at the lumbar vertebrae, femoral neck and total hip reached a plateau at 22 years of age. The peak value of BMD at these 3 sites was 1.209+/-0.175, 1.098+/-0.177 and 1.122+/-0.151 (g/cm2), respectively. Stepwise regression analysis showed that age and weight most contributed to the variance in BMD (P<0.001). The average age when reaching peak BMD in this study is earlier than the ages reported in previous studies, and the value of peak BMD is higher than that reported previously in Chinese males. This study provides the newest peak BMD data on Chinese men. PMID- 21984399 TI - Effect of astaxanthin on cycling time trial performance. AB - We examined the effect of Astaxanthin (AST) on substrate metabolism and cycling time trial (TT) performance by randomly assigning 21 competitive cyclists to 28 d of encapsulated AST (4 mg/d) or placebo (PLA) supplementation. Testing included a VO2max test and on a separate day a 2 h constant intensity pre-exhaustion ride, after a 10 h fast, at 5% below VO2max stimulated onset of 4 mmol/L lactic acid followed 5 min later by a 20 km TT. Analysis included ANOVA and post-hoc testing. Data are Mean (SD) and (95% CI) when expressed as change (pre vs. post). Fourteen participants successfully completed the trial. Overall, we observed significant improvements in 20 km TT performance in the AST group (n=7; -121 s; 95% CI, -185, -53), but not the PLA (n=7; -19 s; 95% CI, -84, 45). The AST group was significantly different vs. PLA (P<0.05). The AST group significantly increased power output (20 W; 95% CI, 1, 38), while the PLA group did not (1.6 W; 95% CI, 17, 20). The mechanism of action for these improvements remains unclear, as we observed no treatment effects for carbohydrate and fat oxidation, or blood indices indicative of fuel mobilization. While AST significantly improved TT performance the mechanism of action explaining this effect remains obscure. PMID- 21984400 TI - Serum levels of S-100B after recreational scuba diving. AB - Recreational scuba diving is a sport of increasing popularity. Previous studies indicating subtle brain injury in asymptomatic divers imply a cumulative effect of minor neural insults in association with diving for professional and/or recreational purposes, over the long-term. This is the first study to investigate putative neural tissue burden during recreational scuba diving by measuring circulating levels of S-100B, a sensitive biomarker of brain injury. 5 male divers performed 3 consecutive dives under conservative recreational diving settings (maximum depth 15 m, duration of dive 56 min, ascend rate 1.15 m/min) with an interval of 12 h between each session. Although a small increase in serum S-100B levels after each dive was apparent, this increase did not quite reach statistical significance (p=0.057). Moreover, no abnormal S-100B values were recorded (mean baseline: 0.06 MUg/L, mean post-dive: 0.086 MUg/L) and no effect of the 3 consecutive dives on changes in S-100B levels was detected. These results suggest that under the experimental conditions tested, diving does not seem to have a discernible and/or cumulative impact on central nervous system integrity. The extent to which variable diving settings and practices as well as individual susceptibility factors underlie putative neural tissue burden in asymptomatic divers, remains to be established. PMID- 21984401 TI - A test for determining endurance capacity in fencers. AB - Until now endurance in fencers has been tested by non-specific ergometer tests even though the movement patterns during fencing are considerably different. The aim of the study was to evaluate a newly developed fencing-specific endurance test (FET). 2 studies were carried out: 28 fencers were tested by FET with fencing-specific footwork and incremental tests on cycle (CE) and treadmill ergometer (TM) in a random order. Afterwards fencing bouts (BOU) were conducted to determine specific physical load. Blood lactate and heart rates were measured. In a second study another group of 18 international and 20 national level fencers conducted FET to explore differences between groups. Comparison of CE, TM, FET and BOU revealed a significant correlation between FET and BOU (r=0.80, p<0.01), heart rates during CE and TM were significantly lower than in bouts (p<0.01). Performance at CE and TM hardly correlated with FET (r=0.30, p<0.05; r=0.31, p<0.05). Elite-fencers showed significantly better performance than non-elite fencers in FET (p<0.01). FET was suitable for determining specific endurance in fencers, allows a better assessment of physical demands during bouts than conventional ergometry and can be used to distinguish between fencers of different levels. PMID- 21984402 TI - COMMUNITY SERVICES AND OUT-MIGRATION. AB - This paper investigates the relationship between changing community context and out-migration in one of today's poor countries, seeking to document the various mechanisms by which infrastructure affects the migratory behavior. We focus on the expansion of social and physical facilities and services near to rural people's homes, including transportation, new markets, employment, schools, health clinics, and mass media outlets such as movie halls. We draw upon detailed data from Nepal to estimate the hypothesized effects. The direct effects of expanding economic and human capital infrastructure are clearly negative, reducing out-migration. However, increased economic infrastructure is associated with a greater accumulation of human and social capital among respondents and their parents. Through these intervening mechanisms, economic and social infrastructure increased the odds of migrating out. These results reveal the often countervailing nature of short- and long-term effects of economic and social change and the complex pathways influencing migration outcomes. PMID- 21984403 TI - Clinical and biological correlates of adolescent anorexia nervosa with impaired cognitive profile. AB - Some neuropsychological studies of anorexia nervosa (AN) have yielded conflicting results, and it has been established that not all adult patients with AN are cognitively impaired. The objective of this study is to determine the percentage of adolescents with AN who present worse cognitive functioning according to neuropsychological criteria of cognitive impairment, and to study their clinical characteristics. Thirty-seven adolescents (11-18 years) with a diagnosis of AN in an acute state of the illness and with low body mass index (BMI) were compared with 41 healthy subjects of the same sex and similar age and intelligence using a comprehensive neuropsychological battery. Overall, AN patients took longer to copy Rey's Figure than the control group (p = 0.001). Thirty per cent of patients showed impaired neuropsychological functioning (defined as scoring two standard deviations lower than the average or lower than their intelligence level in two tasks) with worse performance on visuo-spatial tasks. This subgroup of patients presented lower BMI (p = 0.023) and higher trait anxiety (p = 0.028). The performance of adolescents in an acute state of AN was similar to that of the healthy control group, with the exception of lower time to completion in copying a complex figure. However, cognitive performance varied in these patients, being clearly impaired in one-third of the sample. The cognitive impairment subgroup showed lower BMI and higher anxiety. Longitudinal follow-up studies are necessary to assess the stability of this profile after longer treatment periods. PMID- 21984404 TI - Relationship between serum calcium and magnesium concentrations and metabolic syndrome diagnostic components in middle-aged Korean men. AB - It is thought that calcium and magnesium may be related to metabolic disorders such as obesity and metabolic syndrome; however, to date, there have been few studies investigating the association between serum calcium and magnesium levels and metabolic syndrome in middle-aged male adults. We aimed to investigate the association between serum calcium and magnesium levels and metabolic syndrome in Korean middle-aged male adults. Study subjects included 213 men aged 30~60 years. MetS risk score is determined by adding the number of risk factors, waist circumference, triacylglyceride (TG), HDL cholesterol, glucose, and blood pressure (BP). The study population was divided into three groups according to the MetS risk score: group I (MetS risk score <=1; n = 106), group II (MetS risk score = 2; n = 51), and group III (MetS risk score >=3; n = 56). The serum Ca, according to increase of MetS risk score, was significantly higher (p < 0.001), and there was no significant difference in serum Mg concentration among the three groups. Subjects with high TG and high BP had higher serum calcium levels than those without such abnormalities. Subjects with higher glucose had lower serum magnesium levels than those without such abnormality. The correlation analysis indicated that the serum Ca had positive correlations with the MetS risk score (r = 0.1769, p < 0.01), serum TG (r = 0.2516, p < 0.001), and DBP (r = 0.2246, p < 0.01). The correlation analysis indicated that the serum Mg had an inverse relationship with serum glucose (r = -0.2404, p < 0.001). In conclusion, serum Ca had positive association with TG and BP, while serum Mg had negative association with serum glucose after adjusting age and BMI among the middle-aged Korean male adults. PMID- 21984405 TI - Characteristics and kinetics of iron release from the ferritin under the EGCG reduction. AB - The mechanism of iron release from ferritin in vivo is still unclear even though it represents a key step of the metabolism of iron in vivo. Here, both interaction intensity and binding stability between epigallocatechin gallate (EGCG) from tea and liver ferritin of Dasyatis akajei (DALF) were investigated using UV-visible, fluorescence and circular dichroism (CD) spectrometry, respectively. The results indicated that EGCG could reduce the iron within the ferritin shell directly in the absence of chemical reducers such as Na(2)S(2)O(4), but this process was strictly pH-dependent, and the rate of iron release is faster at low pH than at high pH. The kinetic study of iron release showed that this process fitted the law of zero order reaction, which differed from that of first order reaction by various chemical reducers such as Vitamin C. In addition, Both fluorescence and CD spectrometry were further used to study the reduction mechanism of iron release in vitro, showing that there was a slight conformation change of the ferritin shell during EGCG reduction because of a complex formation of DALF-EGCG. It appears that chemical reducers with large molecular sizes reduce the iron across the protein shell by the way of an electron transfer pathway (ETP). A novel pathway for iron release from DALF with EGCG reduction is suggested to explain for a reductive route of iron metabolism by biological reducers in vivo. PMID- 21984406 TI - Household emergency preparedness: a literature review. AB - Global policies on disaster risk reduction have highlighted individual and community responsibilities and roles in reducing risk and promoting coping capacity. Strengthening local preparedness is viewed as an essential element in effective response and recovery. This paper presents a synthesis of available literature on household preparedness published over the past 15 years. It emphasizes the complexity of preparedness, involving personal and contextual factors such as health status, self-efficacy, community support, and the nature of the emergency. In addition, people require sufficient knowledge, motivation and resources to engage in preparedness activities. Social networks have been identified as one such resource which contributes to resilience. A predominant gap in the literature is the need for evidence-informed strategies to overcome the identified challenges to household preparedness. In particular, the construct of social capital and how it can be used to foster individual and community capacity in emergency situations requires further study. PMID- 21984407 TI - Psychiatrist characteristics related to patient outcome in Japan. AB - We evaluated psychiatric care in terms of the relationship between patient outcome (length of stay, Global Assessment of Functioning (GAF) at discharge, GAF difference, and GAF change per day) and psychiatrist characteristics (gender and years in psychiatric practice) in patients with schizophrenia, schizotypal, or delusional disorders (ICD-10 codes F20-F29) and in those with mood disorders (ICD 10 codes F30-F39). The sample consisted of inpatients discharged from an institute in Japan between April 2007 and March 2008. Multivariate analyses were performed to identify patient and psychiatrist characteristics related to outcome. We found that psychiatrist characteristics, such as gender and years in practice, were associated with GAF-related outcomes in patients in the F20-F29 and F30-F39 code groups (P < 0.05, P < 0.001, respectively). Patient characteristics and clinical factors such as GAF at admission, ward type, arrival by ambulance, admission type, seclusion, restraint, diagnosis, and patient age, were associated with outcome in both diagnostic groups. These findings show that gender and years in psychiatric practice had a significant effect on psychiatric patient outcome. Further studies in multiple institutes using a follow-up design are necessary to verify these findings. PMID- 21984408 TI - R. J. Reynolds goes international with new dissolvable tobacco products. PMID- 21984409 TI - Effects of dislocation density and sample-size on plastic yielding at the nanoscale: a Weibull-like framework. AB - Micro-compression tests have demonstrated that plastic yielding in nanoscale pillars is the result of the fine interplay between the sample-size (chiefly the diameter D) and the density of bulk dislocations rho. The power-law scaling typical of the nanoscale stems from a source-limited regime, which depends on both these sample parameters. Based on the experimental and theoretical results available in the literature, this paper offers a perspective about the joint effect of D and rho on the yield stress in any plastic regime, promoting also a schematic graphical map of it. In the sample-size dependent regime, such dependence is cast mathematically into a first order Weibull-type theory, where the power-law scaling the power exponent beta and the modulus m of an approximate (unimodal) Weibull distribution of source-strengths can be related by a simple inverse proportionality. As a corollary, the scaling exponent beta may not be a universal number, as speculated in the literature. In this context, the discussion opens the alternative possibility of more general (multimodal) source strength distributions, which could produce more complex and realistic strengthening patterns than the single power-law usually assumed. The paper re examines our own experimental data, as well as results of Bei et al. (2008) on Mo alloy pillars, especially for the sake of emphasizing the significance of a sudden increase in sample response scatter as a warning signal of an incipient source-limited regime. PMID- 21984410 TI - Synthesis and luminescence properties of a blue-emitting Sr3.5Y6.5O2(PO4)1.5SiO4(4.5) :Eu2+ phosphor. AB - A novel blue-emitting Sr3.5Y6.5O2(PO4)1.5SiO4(4.5) :Eu2+ phosphor was synthesized via a solid-state reaction. Powder X-ray diffraction (XRD) analysis demonstrated that the Sr3.5Y6.5O2(PO4)1.5(SiO4)4.5 host had a hexagonal crystal structure in the space group P6(3) /m and unit cell parameters a = 9.418 A, c = 6.900 A. The as-prepared phosphor showed a blue emission and all the main emission peaks were located at around 466 nm for different excitation wavelengths of 297, 333 and 391 nm. The temperature dependence of the photoluminescence property was investigated in the range 20-250 degrees C, and the emission intensity decreased to 71% of the initial value at room temperature on increasing the temperature to 150 degrees C. According to the classical theory of fluorescent thermal quenching, the activation energy (DeltaE) for the thermal quenching luminescence of the as prepared Sr3.45Y6.5O2(PO4)1.5(SiO4)4.5 :0.05Eu2+ phosphor was determined to be 0.20 eV. PMID- 21984411 TI - Photocatalytic growth of dendritic silver nanostructures as SERS substrates. AB - We report a one-step photocatalytic synthesis method of dendritic silver nanostructures. These self-organised structures show an excellent Raman enhancement enabling the detection of analytes from dilute solutions by surface enhanced Raman spectroscopy. PMID- 21984412 TI - Phosphorylation of SRSF1 is modulated by replicational stress. AB - DNA ligase I-deficient 46BR.1G1 cells show a delay in the maturation of replicative intermediates resulting in the accumulation of single- and double stranded DNA breaks. As a consequence the ataxia telangiectasia mutated protein kinase (ATM) is constitutively phosphorylated at a basal level. Here, we use 46BR.1G1 cells as a model system to study the cell response to chronic replication-dependent DNA damage. Starting from a proteomic approach, we demonstrate that the phosphorylation level of factors controlling constitutive and alternative splicing is affected by the damage elicited by DNA ligase I deficiency. In particular, we show that SRSF1 is hyperphosphorylated in 46BR.1G1 cells compared to control fibroblasts. This hyperphosphorylation can be partially prevented by inhibiting ATM activity with caffeine. Notably, hyperphosphorylation of SRSF1 affects the subnuclear distribution of the protein and the alternative splicing pattern of target genes. We also unveil a modulation of SRSF1 phosphorylation after exposure of MRC-5V1 control fibroblasts to different exogenous sources of DNA damage. Altogether, our observations indicate that a relevant aspect of the cell response to DNA damage involves the post translational regulation of splicing factor SRSF1 which is associated with a shift in the alternative splicing program of target genes to control cell survival or cell death. PMID- 21984413 TI - Overcoming natural replication barriers: differential helicase requirements. AB - DNA sequences that form secondary structures or bind protein complexes are known barriers to replication and potential inducers of genome instability. In order to determine which helicases facilitate DNA replication across these barriers, we analyzed fork progression through them in wild-type and mutant yeast cells, using 2-dimensional gel-electrophoretic analysis of the replication intermediates. We show that the Srs2 protein facilitates replication of hairpin-forming CGG/CCG repeats and prevents chromosome fragility at the repeat, whereas it does not affect replication of G-quadruplex forming sequences or a protein-bound repeat. Srs2 helicase activity is required for hairpin unwinding and fork progression. Also, the PCNA binding domain of Srs2 is required for its in vivo role of replication through hairpins. In contrast, the absence of Sgs1 or Pif1 helicases did not inhibit replication through structural barriers, though Pif1 did facilitate replication of a telomeric protein barrier. Interestingly, replication through a protein barrier but not a DNA structure barrier was modulated by nucleotide pool levels, illuminating a different mechanism by which cells can regulate fork progression through protein-mediated stall sites. Our analyses reveal fundamental differences in the replication of DNA structural versus protein barriers, with Srs2 helicase activity exclusively required for fork progression through hairpin structures. PMID- 21984414 TI - The RNA recognition motif protein RBM11 is a novel tissue-specific splicing regulator. AB - Mammalian tissues display a remarkable complexity of splicing patterns. Nevertheless, only few examples of tissue-specific splicing regulators are known. Herein, we characterize a novel splicing regulator named RBM11, which contains an RNA Recognition Motif (RRM) at the amino terminus and a region lacking known homology at the carboxyl terminus. RBM11 is selectively expressed in brain, cerebellum and testis, and to a lower extent in kidney. RBM11 mRNA levels fluctuate in a developmentally regulated manner, peaking perinatally in brain and cerebellum, and at puberty in testis, in concomitance with differentiation events occurring in neurons and germ cells. Deletion analysis indicated that the RRM of RBM11 is required for RNA binding, whereas the carboxyl terminal region permits nuclear localization and homodimerization. RBM11 is localized in the nucleoplasm and enriched in SRSF2-containing splicing speckles. Transcription inhibition/release experiments and exposure of cells to stress revealed a dynamic movement of RBM11 between nucleoplasm and speckles, suggesting that its localization is affected by the transcriptional status of the cell. Splicing assays revealed a role for RBM11 in the modulation of alternative splicing. In particular, RBM11 affected the choice of alternative 5' splice sites in BCL-X by binding to specific sequences in exon 2 and antagonizing the SR protein SRSF1. Thus, our findings identify RBM11 as a novel tissue-specific splicing factor with potential implication in the regulation of alternative splicing during neuron and germ cell differentiation. PMID- 21984415 TI - Molecular architecture of a multifunctional MCM complex. AB - DNA replication is strictly regulated through a sequence of steps that involve many macromolecular protein complexes. One of them is the replicative helicase, which is required for initiation and elongation phases. A MCM helicase found as a prophage in the genome of Bacillus cereus is fused with a primase domain constituting an integrative arrangement of two essential activities for replication. We have isolated this helicase-primase complex (BcMCM) showing that it can bind DNA and displays not only helicase and primase but also DNA polymerase activity. Using single-particle electron microscopy and 3D reconstruction, we obtained structures of BcMCM using ATPgammaS or ADP in the absence and presence of DNA. The complex depicts the typical hexameric ring shape. The dissection of the unwinding mechanism using site-directed mutagenesis in the Walker A, Walker B, arginine finger and the helicase channels, suggests that the BcMCM complex unwinds DNA following the extrusion model similarly to the E1 helicase from papillomavirus. PMID- 21984416 TI - The genotoxic and anti-genotoxic effects of Stachys petrokosmos leaf extract in human lymphocytes using microsomal fractions. AB - The genotoxic and anti-genotoxic effects of Stachys petrokosmos leaf extracts (Sp) were investigated in human lymphocytes. The cells were treated with 1.5, 3.0 and 6.0 MUL/mL concentrations of Sp leaf extracts for 24 and 48 h treatment periods in the absence and presence of metabolic activator (S9mix). In the absence of S9mix, Sp alone did not induce chromosome aberrations and formation of micronucleus while inducing the mean sister chromatid exchange at the highest concentration. In addition, Sp decreased the mutagenic effect of mitomycin-c. Sp alone showed a cytotoxic effect determined by a decrease in the proliferation index, mitotic index and nuclear division index. On the other hand a mixture of Sp and mitomycin-c resulted in a higher cytotoxic effect especially for 48 h treatment period. In the presence of S9mix, Sp was not genotoxic and cytotoxic however, it showed an anti-genotoxic effect by decreasing the effects of cyclophosphamide. PMID- 21984417 TI - A method for the automatic quantification of the completeness of pulmonary fissures: evaluation in a database of subjects with severe emphysema. AB - OBJECTIVES: To propose and evaluate a technique for automatic quantification of fissural completeness from chest computed tomography (CT) in a database of subjects with severe emphysema. METHODS: Ninety-six CT studies of patients with severe emphysema were included. The lungs, fissures and lobes were automatically segmented. The completeness of the fissures was calculated as the percentage of the lobar border defined by a fissure. The completeness score of the automatic method was compared with a visual consensus read by three radiologists using boxplots, rank sum tests and ROC analysis. RESULTS: The consensus read found 49% (47/96), 15% (14/96) and 67% (64/96) of the right major, right minor and left major fissures to be complete. For all fissures visually assessed as being complete the automatic method resulted in significantly higher completeness scores (mean 92.78%) than for those assessed as being partial or absent (mean 77.16%; all p values <0.001). The areas under the curves for the automatic fissural completeness were 0.88, 0.91 and 0.83 for the right major, right minor and left major fissures respectively. CONCLUSIONS: An automatic method is able to quantify fissural completeness in a cohort of subjects with severe emphysema consistent with a visual consensus read of three radiologists. KEY POINTS: * Lobar fissures are important for assessing the extent and distribution of lung disease * Modern CT allows automatic lobar segmentation and assessment of the fissures * This segmentation can also assess the completeness of the fissures. * Such assessment is important for decisions about novel therapies (eg for emphysema). PMID- 21984418 TI - Percutaneous removal of sentinel lymph nodes in a swine model using a breast lesion excision system and contrast-enhanced ultrasound. AB - OBJECTIVES: To investigate the feasibility of percutaneous removal of the entire sentinel lymph node (SLN) in an animal model using a breast lesion excision system after identifying these nodes using contrast-enhanced ultrasound (CEUS) and intradermal microbubbles. METHODS: Animal studies approval was obtained. SLNs were identified using CEUS and intradermal injection of microbubbles in two young pigs. Microbubbles were mixed with blue dye and injected around the mammary papillae to access lymphatic drainage to the superficial inguinal lymph nodes. When enhancing nodes were identified, the breast lesion excision system (BLES) was used to remove these nodes percutaneously. Both animals then underwent surgical lymph node dissection. Histopathological examination of all the samples was performed. RESULTS: Removal of the entire SLN was successful in three groins in the pigs. All three nodes were stained with blue dye. No other stained nodes were observed in the node dissection specimens. The nodal architecture of removed lymph nodes was well preserved on microscopy. There were no signs of excess trauma within the biopsy bed. CONCLUSION: The results obtained from the swine model demonstrated that it is feasible to remove the entire SLN percutaneously under the guidance of CEUS and microbubbles. KEY POINTS: Intradermal injection of microbubbles and CEUS can identify sentinel lymph nodes * Ultrasound could then guide percutaneous removal of intact and complete SLNs * We have shown this was feasible in pigs but not yet in humans * This technique may eventually have the potential to reduce futile SLN biopsies. PMID- 21984419 TI - Origin of pancreatic ductal adenocarcinoma from atypical flat lesions: a comparative study in transgenic mice and human tissues. AB - Pancreatic ductal adenocarcinoma (PDAC) and its precursor lesions, pancreatic intraepithelial neoplasia (PanIN), display a ductal phenotype. However, there is evidence in genetically defined mouse models for PDAC harbouring a mutated kras under the control of a pancreas-specific promoter that ductal cancer might arise in the centroacinar-acinar region, possibly through a process of acinar-ductal metaplasia (ADM). In order to further elucidate this model of PDAC development, an extensive expression analysis and molecular characterization of the putative and already established (PanIN) precursor lesions were performed in the Kras(G12D/+) ; Ptf1a-Cre(ex1/+) mouse model and in human tissues, focusing on lineage markers, developmental pathways, cell cycle regulators, apomucins, and stromal activation markers. The results of this study show that areas of ADM are very frequent in the murine and human pancreas and represent regions of increased proliferation of cells with precursor potential. Moreover, atypical flat lesions originating in areas of ADM are the most probable precursors of PDAC in the Kras(G12D/+); Ptf1a-Cre(ex1/+) mice and similar lesions were also found in the pancreas of three patients with a strong family history of PDAC. In conclusion, PDAC development in Kras(G12D/+); Ptf1a-Cre(ex1/+) mice starts from ADM and a similar process might also take place in patients with a strong family history of PDAC. PMID- 21984420 TI - Rhamnolipid-producing thermophilic bacteria of species Thermus and Meiothermus. AB - Novel rhamnolipid-producing strains of three thermophilic bacteria, Thermus sp., T. aquaticus and Meiothermus ruber were identified that have not been previously described as rhamnolipid producers. Rhamnolipids were extracted from supernatant and further purified by thin-layer chromatography. Mass spectrometry with negative electrospray ionization revealed 77 rhamnolipid homologues varying in chain length and unsaturation. Tandem mass spectrometry identified mono rhamnolipid and di-rhamnolipid homologues containing one or two 3-hydroxy-fatty acids, saturated, monounsaturated or diunsaturated, even- or odd-chain, up to unusual long chains with 24 carbon atoms. The stereochemistry of rhamnose was L and that of 3-hydroxy-fatty acids was R, the position of double bonds in monoenoic acids was cis omega-9. All three strains produced a rhamnolipid that differs in structure from Pseudomonas aeruginosa rhamnolipids and exhibits excellent surfactant properties. Importantly, in comparison to P. aeruginosa both strains, i.e., Thermus and Meiothermus, are Biosafety level 1 microorganisms and are not pathogenic to humans. PMID- 21984421 TI - [Continuing education of AG (Working Group) curriculum of the DGOU (German Society of Orthopedics and Trauma Surgery]. PMID- 21984422 TI - [Total hip arthroplasty with shortening subtrochanteric osteotomy and custom-made prosthesis in Crowe type IV developmental dysplasia]. AB - AIM: Total hip arthroplasty in patients with a Crowe type IV developmental dysplasia is a technically demanding procedure with a higher complication rate compared to a standard total hip replacement. Specific anatomic features and the necessity of a femoral shortening osteotomy are the reasons for more complications. In this retrospective study we intended to find out whether the use of a custom-made stem based on a CT scan will lead to a better outcome including a lower complication rate. MATERIAL UND METHOD: From 2003 to 2010 we implanted a cementless CTX(r) individual stem in combination with a subtrochanteric Z-shaped shortening osteotomy in 25 patients with a high hip dislocation, four of them were men (one bilateral) and 16 women (four bilateral). Mean age of the patients was 44.6 years. In all cases the cup was implanted at the level of the anatomic hip centre. Patients were followed with a clinical and radiographic assessment. The morphology of the femur was analysed by CT scans. RESULTS: The average amount of femoral shortening was 3.4 cm (max. 4.2/min. 2.6 cm). Lengthening of the leg was achieved with an average of 3.8 cm (max. 4.4/min. 3.2 cm). The remaining leg length discrepancy was 0.8 cm (max. 1.2/min. 0.4 cm). In none of the cases did an intraoperative fracture of the femur occur, either in the proximal or in the distal part of the femur. Enlargement of the intramedullary canal was not necessary in any case. The planned depth of the prosthesis could be achieved in all patients. We did not observe any problems with wound healing in our patients. The average Harris hip score was 90 (83 up to 100). Additional cerclage wires are not necessary with this technique when the osteotomy is well adapted. After complete healing the osteotomy can just be noticed by a certain hypertrophy of the cortical bone. In our cases we had a complication rate of 16 %, significantly lower in comparison to literature values. CONCLUSIONS: Total hip arthroplasty in type IV developmental dysplasia with a custom-made stem based on a CT scan is a procedure that respects the special anatomic features preoperatively und is able to correct the deformity with the individually manufactured prosthesis. High femoral anteversion is corrected at the level of the neck of the stem. There is no necessity for a derotation at the level of the osteotomy. The osteotomy is stabilised by the Z shape and through a perfect intramedullary fit of the stem. The anatomic shape of the subtrochanteric region is perfectly suitable to perform a femoral shortening. PMID- 21984423 TI - [Different pathoanatomic circumstances in bony lumbar foraminal stenosis have no influence on surgical outcome]. AB - OBJECTIVES: The purpose of this prospective observational study was to evaluate the clinical efficacy of nerve decompression in bony foraminal stenosis in different pathoanatomical circumstances. MATERIAL AND METHODS: Thirty-three consecutive patients (mean age: 63 years) were evaluated. All had leg-dominant monoradicular pain and were treated via a midline approach (lateral foraminotomy, with caudal resection of the pedicle in selected cases). Thirteen patients (39 %) had undergone prior lumbar surgery. The patients were divided into four pathoanatomic groups: (A) facet joint hypertrophy, n = 16; (B) dorsolateral spondylosis, n = 7; (C) height reduction of intervertebral disc, n = 3; (D) mixed group, n = 7. The clinical outcome was graded using a modified Prolo scale (pain and medication) and a visual analogue scale (VAS) after 2 and 12 months. RESULTS: Based on the Prolo scale score, an excellent (n = 18) or good (n = 12) outcome was achieved in 91 % of the patients. There were no outcome differences among the four pathoanatomic groups. However, the groups B, C and D are small. Three patients in group B required revision surgery because of osteophytes in the transition area of the intra- and extraforaminal regions. All but one (97 %) of the patients experienced significant leg pain reduction following surgery as assessed by VAS (including the three revisions). No statistically significant associations were found between back pain, symptom duration, previous surgery, segment level, or pediculotomy and the outcome. There were no surgery-related complications. CONCLUSIONS: Foraminal decompression alone for leg-dominant symptoms is a clinically effective procedure in the majority of patients without differences in the four pathoanatomic groups. PMID- 21984424 TI - [Injuries to the upper cervical medulla in severe brain injuries]. AB - BACKGROUND: Cranial magnetic resonance imaging (MRI) was performed in 250 patients who had been unconscious post-trauma for at least 24 hours. The frequency and the characteristics of injuries to the upper cervical myelon were determined. PATIENTS AND METHODS: Between 1996 and 2009, MRI was carried out within 8 days of trauma. RESULTS: No lesions of the upper cervical medulla were found without accompanying damage to the medulla oblongata. Two groups were found to have a lesion in the upper cervical myelon. (i) In 3.2 % of the patients in a state of deep coma MRI revealed lesions in the entire brain stem. These died without waking from coma. (ii) 2 % of the patients were found to have additional damage to the distal medulla oblongata. These victims of high-speed traumas awoke from coma after 2-3 days. They revealed frontal contusions of the brain and traumatic subarachnoidal hemorrhages. Injuries to the bony upper cervical spine and/or the skull base were frequent. Four of them died, one patient survived with severe disabilities. CONCLUSION: Two types of lesions involving the upper cervical myelon could be differentiated, both of which occur only in association with lesions in the medulla oblongata. PMID- 21984426 TI - [Outpatient treatment of metacarpal and phalangeal fractures leads to similar outcomes compared to inpatient treatment]. AB - Metacarpal and phalangeal fracture fixation may be conducted in ambulatory or inpatient settings. However, to date, little is known about the outcomes of the surgical treatment of metacarpal and phalangeal fractures in the two population groups. The aim of this study was to compare the surgical outcomes of patients undergoing treatment for metacarpal and phalangeal fractures in the ambulatory setting as compared to those in in-hospital settings. All patients who were surgically treated for metacarpal and phalangeal fractures at our institution were enrolled in this study. All patients treated non-surgically, as well as those who had sustained open fractures, were excluded from the study. A total of 85 patients met our inclusion criteria. Based on the length of hospital stay, patients were divided into two groups: inpatient (> 24 hours) and outpatient (< 24 hours). Fifty-three out of the eighty-five patients were available for follow up examination. Patients were re-evaluated at a mean 17.9 months (range: 4-48 months; SD = 10 months) after surgery. Physical function in everyday life and specific hand function were compared between the groups using the DASH and Cooney outcome questionnaires. Range of motion of the affected side was measured using a standard goniometer and was evaluated as a proportion of total active motion (% TAM) relative to the contralateral uninjured side. Complication rates were calculated and compared between groups. There were no differences for the DASH outcome scores for phalangeal and metacarpal fractures on comparing both groups. There was also no statistically significant difference for the mean Cooney score for phalangeal fractures in both groups. The inpatient group had a significantly higher mean Cooney score (mean: 93.5; range, 70-100; SD 8.8; 95 % CI = 87.2, 99.8) after metacarpal fracture fixation than the outpatient group (mean: 82.5; range: 55-100; SD 14.5; 95 % CI = 75.3, 89.7) (p = 0.01). There was no statistically significant difference on comparing the mean proportion of total active motion (% TAM) relative to the contralateral uninjured side between the inpatient and outpatient groups (p > 0.05). The overall complication rate was 20.7 % (n = 11). The most common complication was postoperative infection with six cases (three inpatients; three outpatients). Outpatient surgical treatment of metacarpal and phalangeal fractures results in similar outcomes compared to inpatient treatment. Outpatient treatment of metacarpal and phalangeal fractures should be considered whenever possible. PMID- 21984425 TI - [Diagnostic value of CT discography in unclear radiculopathy]. AB - A clinically evident radiculopathy without correlation in the imaging studies represents a serious problem regarding the indication, planning and execution of an operative procedure for its treatment. Both the diagnosis and treatment of such cases are deemed to be difficult without clear morphological correlation. Moreover, the surgeon lacks an important basis for the adequate planning and above all the justification of surgical treatment. Although discography with post discographic computer tomography (CT discography) is still controversially discussed as an invasive diagnostic measure, the literature shows that this method is not only useful but also indispensable in certain cases. Based on these findings and our own empirical data, we recommend CT discography to be considered for imaging in patients suffering from lumbar radiculopathy with equivocal or insufficient MRI findings. The technique allows an accurate diagnosis and precise planning of a targeted surgical intervention such as endoscopic sequestrotomy or decompression. PMID- 21984427 TI - [An educational skills programme for undergraduate training in orthopaedic and trauma surgery]. AB - INTRODUCTION: Practical training on clinical cases and work with patients is one of the most important steps within the educational programme of undergraduates. Until now a general programme with specific learning targets for undergraduate training in orthopedic and trauma surgery is lacking. MATERIAL AND METHOD: In this article we present an educational skills programme developed by a national committee composed of specialists in the field of orthopaedic and trauma surgery. This programme is based on existing guidelines of German medical universities. RESULTS: The facultative and obligatory guidelines developed by the national committee are presented. CONCLUSION: The presented learning programme contains chapters regarding the increasing requirements within the field of orthopaedic and trauma surgery and provides reproducible contents with the possibility for learning control. PMID- 21984429 TI - [Return to play decisions in professional soccer: a decision algorithm from a team physician's viewpoint]. AB - Especially in competitive professional sports, associated injuries often imply a specific challenge for the physicians responsible for team sports or tournaments. Besides choosing an optimal treatment strategy, in particular the time of absence from sports is of major relevance, not least because especially an "early return to play" may often qualify or disqualify a sports physician in the perception of the involved persons. Time pressure of a club and an athlete as well as an increasing number of matches per season may often result in inadequate rehabilitation periods or doubtful medical decisions and thus an increasing risk of reinjuries. On the other hand, professional sports may often reveal decisive circumstances, e.g., playing a final or special sportive pretensions of an athlete or a club, when - from a medical point of view - the classical "can or cannot play"-decision seams inappropriate. This article describes the borderline dilemma between responsible medical acting, irrespective of any sportive pressure of an athlete or the club and the need to concurrently take account of special circumstances in professional soccer sports. Furthermore, regarding the actual literature, a new decision model is presented which facilitates a responsible and well-balanced return to play decision respecting all the above named aspects. PMID- 21984428 TI - [Impact of magnetic resonance therapy on sickness absence of patients with nerve root irritation following a lumbar disc problem]. AB - BACKGROUND: The prevalence of spinal symptoms in Western industrialised countries ranges up to 80 %. Back pain ranks second among the most common reasons to seek medical advice. The resulting financial burden on the health-care system is proportional to the subjectively experienced pain. The aim of the present study was to determine whether the use of magnetic resonance therapy alters the duration of sickness absence in patients with discogenic radiculopathy. PATIENTS AND METHOD: In a double-blind prospective randomised study, the use of magnetic resonance therapy for back pain in patients with discogenic radiculopathy was evaluated in the context of health economics. Patients aged 20 to 55 years with lumboischialgia and no indication for surgery were included in the study. The primary variable was the number of days of sickness absence in a study group before and after magnetic field therapy, and in a control group. The number of days of sickness absence was determined on the basis of a pain diary and by telephone inquiry. RESULTS: Patients who were treated with an activated magnetic resonance therapy device had significantly fewer days of sickness absence (p = 0.009) when evaluated by personal telephone calls. The duration of sickness absence before therapy was 14.7 days and that after therapy 5.8 days. In contrast, the days of sickness absence in the control group were 7.6 days before therapy and 13.8 days after therapy. The duration of symptoms was negatively correlated with the days of sickness absence. Patients who reported a burden at work had more days of sickness absence (8.3 days) than those with no burden at work (3.2 days). This correlation does not apply to familial burden. The cost effectiveness analysis showed different degrees of compensation of the cost of magnetic resonance therapy, depending on the occupational group. Direct and indirect costs of magnetic resonance therapy were compensated by 16.9 fewer days of sickness absence among workers, 11.4 fewer days of sickness absence among employees, and 9.1 fewer days of sickness absence among civil servants. CONCLUSION: Based on the number of days of sickness absence, the study confirmed that a relatively economical alternative technique is able to provide pain relief as well as benefit the health economy. Unemployed patients or patients who have submitted an application for a pension may be problematic because they may not wish to be pronounced healthy by their doctors. PMID- 21984430 TI - [Ligamentous injuries to the ankle joint]. AB - Injuries to the lateral ankle ligaments are the most common sports injuries. Determination of their severity and exclusion of relevant accompanying injuries requires a subtle clinical and a focussed radiological assessment. Treatment is non-operative and functional in the majority of cases. Consequent application of orthoses limiting supination and proprioceptive training are essential to avoid chronic instability. With recurrent ankle sprains one has to distinguish between functional and mechanical instability. The latter can be treated successfully with anatomic reconstruction and ligamentoplasty in more than 80 % of cases. Extraanatomic tenodeses should be reserved for cases of combined ankle and subtalar instability. Isolated injuries to the medial collateral ligaments are rare. Therefore, osseous injuries or underlying deformities have to be excluded. Isolated deltoid ligament ruptures may be treated non-operatively. Unstable injuries to the distal tibiofibular syndesmosis resulting in a manifest or latent diastasis are treated with open reduction and fixation with two tibiofibular set screws. Anatomic reduction of the distal fibula into the tibial groove is of utmost prognostic relevance and therefore should be reliably proved with either intraoperative 3D fluoroscopy or postoperative CT scanning. For chronic syndesmotic instability an anatomic ligamentoplasty using half the peroneus longus tendon is recommended. PMID- 21984432 TI - Alterations in expression levels of deafness dystonia protein 1 affect mitochondrial morphology. AB - Deafness-Dystonia-Optic Neuropathy (DDON) Syndrome is a rare X-linked progressive neurodegenerative disorder resulting from mutations in the TIMM8A gene encoding for the deafness dystonia protein 1 (DDP1). Despite important progress in identifying and characterizing novel mutations in this gene, little is known about the underlying pathomechanisms. Deficiencies in the biogenesis of hTim23 and consecutive alterations in biogenesis of inner membrane and matrix proteins have been proposed to serve as one possible mechanistic explanation. To shed new light on the role of DDP1 in the biogenesis of mammalian mitochondria, we investigated the effects of reduced or elevated DDP1 levels on mitochondrial dynamics and function. Our results show a reduction in the import of beta-barrel proteins into mitochondria from cells overexpressing DDP1. This effect was not observed when the DDON-related mutant form DDP1-C66W was overexpressed. Live cell microscopy of primary fibroblasts derived from DDON patients and of DDP1 downregulated HeLa cells displayed alterations of mitochondrial morphology with notable extensions in the length of mitochondrial tubules, whereas overexpression of DDP1 induced the formation of hollow spherical mitochondria. Of note, knockdown of the TIMM8A gene by RNA interference did not show an influence on the oxygen respiration rate and the mitochondrial membrane potential. Taken together, these results suggest that alterations in the levels of DDP1 can affect the morphology of mitochondria and thus shed new light on the pathogenic mechanisms of DDON. PMID- 21984431 TI - Methicillin resistant S. aureus in human and bovine mastitis. AB - Staphylococcus aureus is a ubiquitous organism that causes a variety of diseases including mastitis in cattle and humans. High-level resistance of S. aureus to beta-lactams conferred by a mecA gene encoding a modified penicillin binding protein (PBP2a) was first observed in the early 1960's. These methicillin resistant S. aureus (MRSA) have been responsible for both hospital acquired infections (HA-MRSA) and, more recently, community acquired MRSA (CA-MRSA). A small number of human MRSA mastitis cases and outbreaks in maternity or neonatal units have been reported which are generally the result of CA-MRSA. The establishment of the sequence type 398 (ST398) in farm animals, primarily pigs, in the early 2000's has provided a reservoir of infection for humans and dairy cattle, particularly in continental Europe, described as livestock-associated MRSA (LA-MRSA). Prior to the emergence of ST398 there were sporadic reports of MRSA in bovine milk and cases of mastitis, often caused by strains from human associated lineages. Subsequently, there have been several reports describing bovine udder infections caused by ST-398 MRSA. Recently, another group of LA-MRSA strains was discovered in humans and dairy cattle in Europe. This group carries a divergent mecA gene and includes a number of S. aureus lineages (CC130, ST425, and CC1943) that were hitherto thought to be bovine-specific but are now also found as carriage or clinical isolates in humans. The emergence of MRSA in dairy cattle may be associated with contact with other host species, as in the case of ST398, or with the exchange of genetic material between S. aureus and coagulase negative Staphylococcus species, which are the most common species associated with bovine intramammary infections and commonly carry antimicrobial resistance determinants. PMID- 21984433 TI - Deregulation of the A-to-I RNA editing mechanism in psychiatric disorders. AB - Schizophrenia and bipolar disorder (BPD) are common neurodevelopmental disorders, characterized by various life-crippling symptoms and high suicide rates. Multiple studies support a strong genetic involvement in the etiology of these disorders, although patterns of inheritance are variable and complex. Adenosine-to-inosine RNA editing is a cellular mechanism, which has been implicated in mental disorders and suicide. To examine the involvement of altered RNA editing in these disorders, we: (i) quantified the mRNA levels of the adenosine deaminase acting on RNA (ADAR) editing enzymes by real-time quantitative polymerase chain reaction, and (ii) measured the editing levels in transcripts of several neuroreceptors using 454 high-throughput sequencing, in dorsolateral-prefrontal cortices of schizophrenics, BPD patients and controls. Increased expression of specific ADAR2 variants with diminished catalytic activity was observed in schizophrenia. Our results also indicate that the I/V editing site in the glutamate receptor, ionotropic kainate 2 (GRIK2) transcript is under-edited in BPD (type I) patients (45.8 versus 53.9%, P= 0.023). GRIK2 has been implicated in mood disorders, and editing of its I/V site can modulate Ca(+2) permeability of the channel, consistent with numerous observations of elevated intracellular Ca(+2) levels in BPD patients. Our findings may therefore, at least partly, explain a molecular mechanism underlying the disorder. In addition, an intriguing correlation was found between editing events on separate exons of GRIK2. Finally, multiple novel editing sites were detected near previously known sites, albeit most with very low editing rates. This supports the hypothesis raised previously regarding the existence of wide-spread low-level 'background' editing as a mechanism that enhances adaptation and evolvability. PMID- 21984434 TI - Identification of four novel variants that influence central corneal thickness in multi-ethnic Asian populations. AB - Central corneal thickness (CCT) is a highly heritable trait. Genes that significantly influence CCT can be candidate genes for common disorders in which CCT has been implicated, such as primary open-angle glaucoma (POAG) and keratoconus. Because the genetic factors controlling CCT in different Asian populations are unclear, we have built on previous work conducted on Singaporean Indians and Malays and extended our hypothesis to individuals of Chinese descent. We have followed up on all suggestive signals of association with CCT (P < 10( 4)) from the previously reported meta-analysis comprising Indians and Malays in a sample of Chinese individuals (n= 2681). In the combined sample (n= 7711), strong evidence of association was observed at four novel loci: IBTK on chromosome 6q14.1; CHSY1 on chromosome 15q26.3; and intergenic regions on chromosomes 7q11.2 and 9p23 (8.01 * 10(-11) < lambda(GC) corrected P(meta) < 8.72 * 10(-8)). These four new loci explain an additional 4.3% of the total CCT variance across the sample cohorts over and above that of previously identified loci. We also extend on a previous finding at a fifth locus (AKAP13) where a new single-nucleotide polymorphism (rs1821481, P(meta) = 9.99 * 10(-9)) was found to be significantly more informative compared with the previously reported rs6496932 (P(meta) = 3.64 * 10(-5)). Performing association analysis in Asians may lead to the discovery of ethnic-specific genes that control CCT, offering further mechanistic insights into the regulation of CCT. In addition, it may also provide several candidate genes for interrogation for POAG, keratoconus and possible racial/ethnic variations. PMID- 21984435 TI - Insights into molecular recognition of Lewis(X) mimics by DC-SIGN using NMR and molecular modelling. AB - In this work, we have studied in detail the binding of two alpha-fucosylamide based mimics of Lewis(X) to DC-SIGN ECD (ECD = extracellular domain) using STD NMR and docking. We have concluded that the binding mode occurs mainly through the fucose moiety, in the same way as Lewis(X). Similarly to other mimics containing mannose or fucose previously studied, we have shown that both compounds bind to DC-SIGN ECD in a multimodal fashion. In this case, the main contact is the interaction of two hydroxyl groups one equatorial and the other one axial (O3 and O4) of the fucose with the Ca(2+) as Lewis(X) and similarly to mannose-containing mimics (in this case the interacting groups are both in the equatorial position). Finally, we have measured the K(D) of one mimic that was 0.4 mM. Competitive STD NMR experiments indicate that the aromatic moiety provides additional binding contacts that increase the affinity. PMID- 21984437 TI - Surveillance strategy of atrophic gastritis and intestinal metaplasia in a country with a high prevalence of gastric cancer. AB - BACKGROUND: It is not clear which screening examinations are best suited for gastric cancer prevention, especially in patients with atrophic gastritis and intestinal metaplasia. Therefore, we investigated the gastric cancer screening methods and intervals that are performed in clinical practice in an area with a high prevalence of gastric cancer. METHODS: Eighty-seven physicians voted by keypad and discussed the consistency of endoscopic diagnosis of atrophic gastritis and intestinal metaplasia at the Annual Symposium of the Korean College of Helicobacter and Upper Gastrointestinal Research. Additionally, 100 core members of this academic society were asked via e-mail to complete the questionnaires related to screening strategies for gastric cancer. RESULTS: The most common recommendation for the subjects with intestinal metaplasia was an annual endoscopic follow-up (95.5% vs. 80.4% in the expert and non-expert groups, respectively; P = 0.118). Annual endoscopic follow-up was also the most predominant recommendation for atrophic gastritis (95.5% vs. 76.5%; P = 0.092), regardless of the physicians' endoscopic experience, position, and degree of the hospital. However, the correct answer rate for the diagnosis of normal endoscopic findings was only 16.7 and 14.1% in the expert and non-expert groups, respectively (P = 0.883). CONCLUSIONS: The most common practical screening strategy for patients with atrophic gastritis and intestinal metaplasia in Korea was annual endoscopic examination. However, a new program estimating individualized gastric cancer risk might be needed because of the low inter observer agreement in the endoscopic diagnosis of atrophic gastritis and intestinal metaplasia. PMID- 21984438 TI - Circulating vitamin D and colorectal adenoma in asymptomatic average-risk individuals who underwent first screening colonoscopy: a case-control study. AB - BACKGROUND: A higher circulating vitamin D level is inversely associated with the risk of colorectal cancer, but the association with adenoma risk is less clear. AIMS: We examined the association between the circulating 25-hydroxyvitamin D(3) [25(OH)D(3)] concentration and colorectal adenoma in asymptomatic average-risk participants undergoing initial screening colonoscopy. METHODS: The study subjects were comprised of 143 cases of colorectal adenomas and 143 age- and gender-matched controls with normal colonoscopy among the 586 asymptomatic average-risk subjects (median age, 58 years; range, 50-73 years) who underwent first screening colonoscopy and measurement of the serum 25(OH)D(3) between December 2009 and April 2010, consistent with winter months of the region. RESULTS: The mean concentration of serum 25(OH)D(3) in the adenoma and control groups was 20.0 +/- 11.0 ng/ml and 25.0 +/- 20.0 ng/ml, respectively (P = 0.009). Using multivariate analysis, higher levels of 25(OH)D(3) were associated with a statistically significant decreased risk of colorectal adenoma after multivariable adjustment (highest vs. lowest quartile OR 0.38, 95% CI 0.18-0.80, P (trend) = 0.012). The inverse association of circulating 25(OH)D(3) with colorectal adenoma was stronger among the patients with proximal adenoma than that among the patients without proximal adenoma (highest vs. lowest quartile OR 0.29, 95% CI 0.13-0.66, P (trend) = 0.001). CONCLUSIONS: The present study suggests that high levels of circulating vitamin D are associated with a decreased risk of colorectal adenoma, and especially adenoma located in the proximal colon. PMID- 21984436 TI - Molecular mechanisms of Barrett's esophagus. AB - Barrett's esophagus (BE) is defined as the metaplastic conversion of esophageal squamous epithelium to intestinalized columnar epithelium. As a premalignant lesion of esophageal adenocarcinoma (EAC), BE develops as a result of chronic gastroesophageal reflux disease (GERD). Many studies have been conducted to understand the molecular mechanisms of this disease. This review summarizes recent results involving squamous and intestinal transcription factors, signaling pathways, stromal factors, microRNAs, and other factors in the development of BE. A conceptual framework is proposed to guide future studies. We expect elucidation of the molecular mechanisms of BE to help in the development of improved management of GERD, BE, and EAC. PMID- 21984439 TI - Increased frequency of circulating Th17 cells in acute-on-chronic hepatitis B liver failure. AB - BACKGROUND: T helper (Th) 17 cells participate in the pathogenesis of liver diseases but their exact role in acute-on-chronic hepatitis B liver failure (ACHBLF) still remains obscure. AIMS: This present study was aimed to characterize the circulating Th17 cells and to analyze their association with disease progression in ACHBLF. METHODS: This retrospective study consisted of 40 ACHBLF patients, 40 chronic hepatitis B (CHB) patients and 20 healthy controls. The frequency of peripheral Th17 cells and IL-17 mRNA level in peripheral blood mononuclear cells (PBMCs) were estimated by flow cytometry and relative quantitative real-time polymerase chain reaction. RESULTS: We found that the frequency of peripheral Th17 cells, as well as the level of IL-17 mRNA in PBMCs, was significantly increased in ACHBLF patients compared with CHB patients and healthy controls. In ACHBLF patients, the frequency of Th17 cells was positively correlated with serum total bilirubin (r = 0.392, P = 0.012) and model for end stage liver disease scores (r = 0.383, P = 0.015), but negatively correlated with prothrombin activity (r = -0.317, P = 0.046). The same trend was observed as for relative expression of IL-17. Furthermore, the frequency of Th17 cells and IL-17 mRNA level were significantly elevated in non-survivors compared with survivors in ACHBLF patients. CONCLUSIONS: These results suggested that Th17 cells as well as IL-17 might be related with disease severity and prognosis in ACHBLF patients. PMID- 21984442 TI - Comment on the special issue--green tea and cancer. PMID- 21984440 TI - Duodenal and colonic stent placement with 0.025" and 0.035" guidewires is equally safe and effective. AB - BACKGROUND: The overwhelming majority of reported duodenal and colonic SEMS placements in the literature have used the 0.035" guidewire almost to the exclusion of guidewires of other diameters. AIMS: The purpose of this study was to compare technical and clinical outcomes in patients undergoing duodenal or colonic SEMS placement with 0.025" or 0.035" guidewires. METHODS: This was a retrospective study to compare technical and clinical outcomes and complications of patients receiving duodenal or colonic SEMS placement with a 0.035" guidewire to those undergoing placement with a 0.025" guidewire. RESULTS: A total of 34 duodenal and 30 colonic stent placement procedures were performed in 59 patients. Technical success was achieved in all duodenal stent placement procedures. The difference in mean GOOSS score increase after stent placement was not statistically significant between the 0.035" and 0.025" guidewire groups (P = 0.49). Complications were not statistically significantly different between the two groups undergoing gastroduodenal stenting. Technical and clinical success was achieved in all colonic stent placement procedures. There were no statistically significant differences in complication rates between the two groups undergoing colonic stenting. Procedure times were not significantly different using either wire type. CONCLUSIONS: Our study shows that both 0.035" and 0.025" guidewires were equally effective with regards to technical success, clinical success, and with regards to the development of complications. PMID- 21984443 TI - A food matrix reduces digestion and absorption of food allergens in vivo. AB - SCOPE: Food allergy is caused by primary (class 1) food allergens, e.g. Bos d 5 (cow's milk) and Cor a 8 (hazelnut) or secondary (class 2) food allergens, e.g. Mal d 1 (apple). The latter cannot sensitize susceptible individuals but can cause allergy due to immunological cross-reactivity with homologous respiratory allergens. Here, we studied the effects of food matrix on gastrointestinal proteolysis, epithelial transport and in vivo absorption of class 1 and class 2 food allergens. METHODS AND RESULTS: Mal d 1 lost its IgE-reactivity immediately after simulated gastric digestion whereas Bos d 5 and Cor a 8 did not. Only Cor a 8 maintained IgE-binding capacity after simulated intestinal proteolysis. The presence of hazelnut and peanut extracts, which served as protein-rich model food matrices, delayed gastrointestinal degradation and reduced epithelial transport rates of all allergens through CaCo-2 monolayers. Finally, IgE-reactive allergens were assessed at different time points in sera from rats fed with all three allergens with or without hazelnut extract. The levels of all allergens peaked 2 h after animals were fed without matrix and increased over 8 h after feeding. CONCLUSIONS: A protein-rich food matrix delays gastrointestinal digestion and epithelial transport of food allergens and thereby may affect their sensitizing capacity and clinical symptoms. PMID- 21984444 TI - Local coronary flow is associated with an unsuccessful complete block line at the mitral isthmus in patients with atrial fibrillation. AB - BACKGROUND: The addition of a mitral isthmus (MI) block line after pulmonary vein isolation could lead to a favorable outcome of catheter ablation in patients with atrial fibrillation (AF). However, it is sometimes tough to create a complete MI block line, and the cooling effect because of the local coronary flow may prevent the creation of a successful MI block line. METHODS AND RESULTS: This study enrolled 81 AF patients in whom the creation of an MI block line was attempted in those with persistent or pacing-inducible AF after pulmonary vein isolation. A local coronary artery (LCA) across the MI block line was observed in 43 (53%) of 81 patients, and a bidirectional MI block was successfully accomplished in 53 (65%) of 81 patients, at the estimated MI line. The ratio of a successful MI block line was significantly lower in the patients with an LCA than in those without an LCA (42% versus 92%; P<0.001). The mean diameter of the coronary sinus (0.59 +/- 0.18 versus 0.82 +/- 0.22 cm; P<0.001) and length of the estimated MI line (33.4 +/- 9.9 versus 29.4 +/- 7.1 mm; P=0.032) were significantly shorter in the patients with a successful MI block line than in those without a successful MI block line. In the multivariable analysis, an LCA at the MI and a larger coronary sinus diameter were independent risk factors for an unsuccessful MI block line. CONCLUSIONS: Local coronary flow at the MI is associated with an increased incidence of an unsuccessful MI block line. PMID- 21984446 TI - Electrogram fractionation: the relationship between spatiotemporal variation of tissue excitation and electrode spatial resolution. AB - BACKGROUND: Fractionated electrograms are used by some as targets for ablation in atrial and ventricular arrhythmias. Fractionation has been demonstrated to result when there is repetitive or asynchronous activation of separate groups of cells within the recording region of a mapping electrode(s). METHODS AND RESULTS: Using a computer model, we generated tissue activation patterns with increasing spatiotemporal variation and calculated virtual electrograms from electrodes with decreasing resolution. We then quantified electrogram fractionation. In addition, we recorded unipolar electrograms during atrial fibrillation in 20 patients undergoing atrial fibrillation ablation. From these we constructed bipolar electrograms with increasing interelectrode spacing and quantified fractionation. During modeling of spatiotemporal variation, fractionation varied directly with electrode length, diameter, height, and interelectrode spacing. When resolution was held constant, fractionation increased with increasing spatiotemporal variation. In the absence of spatial variation, fractionation was independent of resolution and proportional to excitation frequency. In patients with atrial fibrillation, fractionation increased as interelectrode spacing increased. CONCLUSIONS: We created a model for distinguishing the roles of spatial and temporal electric variation and electrode resolution in producing electrogram fractionation. Spatial resolution affects fractionation attributable to spatiotemporal variation but not temporal variation alone. Electrogram fractionation was directly proportional to spatiotemporal variation and inversely proportional to spatial resolution. Spatial resolution limits the ability to distinguish high-frequency excitation from overcounting. In patients with atrial fibrillation, complex fractionated atrial electrogram detection varies with spatial resolution. Electrode resolution must therefore be considered when interpreting and comparing studies of fractionation. PMID- 21984445 TI - Unique properties of the ATP-sensitive K+ channel in the mouse ventricular cardiac conduction system. AB - Background- The specialized cardiac conduction system (CCS) expresses a unique complement of ion channels that confer a specific electrophysiological profile. ATP-sensitive potassium (K(ATP)) channels in these myocytes have not been systemically investigated. Methods and Results- We recorded K(ATP) channels in isolated CCS myocytes using Cntn2-EGFP reporter mice. The CCS K(ATP) channels were less sensitive to inhibitory cytosolic ATP compared with ventricular channels and more strongly activated by MgADP. They also had a smaller slope conductance. The 2 types of channels had similar intraburst open and closed times, but the CCS K(ATP) channel had a prolonged interburst closed time. CCS K(ATP) channels were strongly activated by diazoxide and less by levcromakalim, whereas the ventricular K(ATP) channel had a reverse pharmacological profile. CCS myocytes express elevated levels of Kir6.1 but reduced Kir6.2 and SUR2A mRNA compared with ventricular myocytes (SUR1 expression was negligible). SUR2B mRNA expression was higher in CCS myocytes relative to SUR2A. Canine Purkinje fibers expressed higher levels of Kir6.1 and SUR2B protein relative to the ventricle. Numeric simulation predicts a high sensitivity of the Purkinje action potential to changes in ATP:ADP ratio. Cardiac conduction time was prolonged by low-flow ischemia in isolated, perfused mouse hearts, which was prevented by glibenclamide. Conclusions- These data imply a differential electrophysiological response (and possible contribution to arrhythmias) of the ventricular CCS to K(ATP) channel opening during periods of ischemia. PMID- 21984447 TI - Utility of diffusion-weighted imaging in the evaluation of liver fibrosis. AB - OBJECTIVES: To evaluate the usefulness of diffusion- weighted MRI (DWI) in the detection and staging of liver fibrosis and inflammation. METHODS: DWI was performed with b-factors of 0, 500 and 1000 s/mm2. ADC values were obtained by placing circular regions of interest in four segments of the liver. Differences between the study (n = 34) and control groups' (n = 25) ADC values were examined. Further, this study investigated if and how ADC values were related to fibrosis stages and histological activity index (HAI) scores. RESULTS: The mean ADC value of the liver was smaller in the study group compared with the control group (P < 0.001). Spearman rho correlation analyses showed lower ADC values were associated with higher fibrosis and HAI scores (P < 0.01). There were statistically significant differences in liver ADC values between each combination of fibrosis stages (e.g. stages 0 and 1, 0 and 2) except for stages 1 and 2. CONCLUSIONS: ADC values prove to be a valuable technique for the diagnosis of liver fibrosis and inflammation. They can also be useful in fibrosis staging, particularly in distinguishing later stages of fibrosis from intermediate and early stages. KEY POINTS: Diffusion Weighted MRI is a promising technique for diagnosis of liver fibrosis. Apparent Diffusion Coefficients provide valuable information for staging of liver fibrosis. DWI may offer alternative to biopsy for assessing liver fibrosis. PMID- 21984448 TI - Radiation dose considerations by intra-individual Monte Carlo simulations in dual source spiral coronary computed tomography angiography with electrocardiogram triggered tube current modulation and adaptive pitch. AB - OBJECTIVES: To evaluate radiation dose levels in patients undergoing spiral coronary computed tomography angiography (CTA) on a dual-source system in clinical routine. METHODS: Coronary CTA was performed for 56 patients with electrocardiogram-triggered tube current modulation (TCM) and heart-rate (HR) dependent pitch adaptation. Individual Monte Carlo (MC) simulations were performed for dose assessment. Retrospective simulations with constant tube current (CTC) served as reference. Lung tissue was segmented and used for organ and effective dose (ED) calculation. RESULTS: Estimates for mean relative ED was 7.1 +/- 2.1 mSv/100 mAs for TCM and 12.5 +/- 5.3 mSv/100 mAs for CTC (P < 0.001). Relative dose reduction at low HR (<=60 bpm) was highest (49 +/- 5%) compared to intermediate (60-70 bpm, 33 +/- 12%) and high HR (>70 bpm, 29 +/- 12%). However lowest ED is achieved at high HR (5.2 +/- 1.5 mSv/100 mAs), compared with intermediate (6.7 +/- 1.6 mSv/100 mAs) and low (8.3 +/- 2.1 mSv/100 mAs) HR when automated pitch adaptation is applied. CONCLUSIONS: Radiation dose savings up to 52% are achievable by TCM at low and regular HR. However lowest ED is attained at high HR by pitch adaptation despite inferior radiation dose reduction by TCM. KEY POINTS: * Monte Carlo simulations allow for individual radiation dose calculations. * ECG-triggered tube current modulation (TCM) can effectively reduce radiation dose. * Slow and regular heart rates allow for highest dose reductions by TCM. * Adaptive pitch accounts for lowest radiation dose at high heart rates. * Women receive higher effective dose than men undergoing spiral coronary CT-angiography. PMID- 21984449 TI - Quantifying differences in hepatic uptake of the liver specific contrast agents Gd-EOB-DTPA and Gd-BOPTA: a pilot study. AB - OBJECTIVES: To develop and evaluate a procedure for quantifying the hepatocyte specific uptake of Gd-BOPTA and Gd-EOB-DTPA using dynamic contrast-enhanced (DCE) MRI. METHODS: Ten healthy volunteers were prospectively recruited and 21 patients with suspected hepatobiliary disease were retrospectively evaluated. All subjects were examined with DCE-MRI using 0.025 mmol/kg of Gd-EOB-DTPA. The healthy volunteers underwent an additional examination using 0.05 mmol/kg of Gd-BOPTA. The signal intensities (SI) of liver and spleen parenchyma were obtained from unenhanced and enhanced acquisitions. Using pharmacokinetic models of the liver and spleen, and an SI rescaling procedure, a hepatic uptake rate, K (Hep), estimate was derived. The K (Hep) values for Gd-EOB-DTPA were then studied in relation to those for Gd-BOPTA and to a clinical classification of the patient's hepatobiliary dysfunction. RESULTS: K (Hep) estimated using Gd-EOB-DTPA showed a significant Pearson correlation with K (Hep) estimated using Gd-BOPTA (r = 0.64; P < 0.05) in healthy subjects. Patients with impaired hepatobiliary function had significantly lower K (Hep) than patients with normal hepatobiliary function (K (Hep) = 0.09 +/- 0.05 min(-1) versus K (Hep) = 0.24 +/- 0.10 min(-1); P < 0.01). CONCLUSIONS: A new procedure for quantifying the hepatocyte-specific uptake of T (1)-enhancing contrast agent was demonstrated and used to show that impaired hepatobiliary function severely influences the hepatic uptake of Gd-EOB-DTPA. KEY POINTS: * The liver uptake of contrast agents may be measured with standard clinical MRI. * Calculation of liver contrast agent uptake is improved by considering splenic uptake. * Liver function affects the uptake of the liver specific contrast agent Gd-EOB-DTPA. * Hepatic uptake of two contrast agents (Gd EOB-DTPA, Gd-BOPTA) is correlated in healthy individuals. * This method can be useful for determining liver function, e.g. before hepatic surgery. PMID- 21984450 TI - Focal adhesion kinase and tumour angiogenesis. AB - Angiogenesis, the formation of new blood vessels from pre-existing ones, is essential for tumour development. It is initiated and regulated by growth factors via their surface receptors, which activate several intracellular signalling pathways in endothelial cells. Cell adhesion molecules, such as integrins, also regulate angiogenesis. Despite these facts, inhibitors of endothelial cell growth factor receptors or integrins have not been as effective as initially hoped in the long-term inhibition of angiogenesis in cancer patients. Signalling downstream of growth factor receptors and integrins converge on the ubiquitously expressed non-receptor tyrosine kinase focal adhesion kinase (FAK). FAK is involved in endothelial cell proliferation, migration and survival, is up regulated in many cancers and has recently been shown to control tumour angiogenesis. Indeed, FAK inhibitors are presently being developed for the treatment of cancer. However, recent studies have indicated the complexities of understanding the precise role for FAK in angiogenesis. Here we have summarized some of the key features of FAK, addressed some of the apparently contradictory roles of this molecule in angiogenesis and provided some perspectives for future studies. PMID- 21984451 TI - Recurrent collapses following permanent pacemaker implantation. PMID- 21984452 TI - Inguinal hernia disease in Africa: a common but neglected surgical condition. AB - BACKGROUND: Hernia surgery is one of the most frequent procedures done by surgeons - paediatric and general surgeons -in the African continent. OBJECTIVE: To review the surgical literature, on the epidemiology, clinical features, treatment and outcome of inguinal hernia surgery in Africa. DATA SOURCE: The search terms used were groin hernias in Africa, hernia surgery in Africa, inguinal hernias in Africa, hernias in adults and hernias in children in Africa using Medline, Cochrane Central Register of Controlled Trials and EMBASE. SELECTION CRITERIA: All journal articles on inguinal hernias performed in Africa and published in the world journals from 1990-2010 were retrieved. DATA EXTRACTION AND ANALYSIS: All articles containing information on inguinal hernias in children and adults were carefully studied for epidemiology, clinical presentation, method of hernia repair, complications (including morbidity and mortality rates) and the future of hernia surgery in Africa. RESULTS: There was an absolute dearth of knowledge of the burden of inguinal hernias in the various communities in Africa, especially, in sub-Saharan Africa. There were non-existent population-based studies in the sub-Saharan context that could inform us about the epidemiology of inguinal hernias and hence estimate the necessity for surgery in Africa. The studies were all clinical in nature and did not reflect the true burden of the disease among Africans. In many of these hospital-based studies, the method of inguinal hernia repair used most was the Bassini repair. Not much was found in the literature about the use of the Lichtenstein tension-free mesh repair of inguinal hernias, the reason being that the mesh was too expensive for the patients to afford. Scarcely, was laparoscopic hernia repair mentioned. CONCLUSION: Based on the clinical studies reviewed, there is a large disease burden of inguinal hernias in Africa. There is, understandably, also a limited surgical capacity to reduce this burden. The authors advocate the formation of an African Hernia Society to partner with corporate and international organisations to make hernias a public health problem and to attempt to determine, using population-based studies, the actual burden of the disease in Africa and then to take modern hernia surgery to most parts of the continent to help reduce the hernia burden, especially its complications. PMID- 21984453 TI - Relationship of reported clinical features of pre-eclampsia and postpartum haemorrhage to demographic and other variables. AB - BACKGROUND: Maternal death and disability remain significant problems in developing countries and are predominantly caused by preeclampsia and postpartum haemorrhage. The diagnostic criteria for preeclampsia and postpartum haemorrhage require medical technologies not readily available in underdeveloped areas. OBJECTIVE: To determine the correlates of pre-eclampsia and postpartum haemorrhage using symptoms in a rural setting. METHODS: This was a cross sectional study in which 577 women from the Kwahu South District of the Eastern Region of Ghana completed questionnaires that sought for signs and symptoms of pre-eclampsia and postpartum haemorrhage in their current or prior pregnancies. The study was conducted over a period of two months, symptoms of pre-eclampsia assessed included headache, visual disturbance, urination, breathing, leg swelling and seizures. For postpartum haemorrhage, the following features were assessed: placenta delivery, length of labour, difficult delivery of placenta, lacerations associated with delivery, size of newborn, headache, visual disturbance and amount of vaginal bleeding. RESULTS: There was a significant association between education and the number of signs and symptoms of preeclampsia, (Chi2 =9.059, =0.018; OR no education vs >7 years=6.8). Mothers with no education were about seven times more likely to have all six signs and symptoms of preeclampsia than those with seven or more years of education. There was no significant association between education and postpartum haemorrhage, (Chi2 = 1.835, = 0.400). However, the OR of 1.59, indicated an inverse association between the two variables. CONCLUSION: The high number of symptoms associated with preeclampsia among women with no formal education strongly supports the need for educational outreach and basic prenatal care in rural Ghana. PMID- 21984454 TI - Asymptomatic bacteriuria among an obstetric population in Ibadan. AB - BACKGROUND: Asymptomatic bacteriuria in pregnancy is the major risk factor for symptomatic urinary tract infection during pregnancy. Screening and identification of bacteriuria during pregnancy have been recommended. OBJECTIVE: To determine the prevalence and pattern of asymptomatic bacteriuria associated with pregnancy. METHODS: The study was a descriptive, cross sectional survey of pattern of asymptomatic bacteriuria among consecutive patients presenting for the first antenatal visit at a University College Hospital, during a period of two months. Relevant information obtained from all the patients recruited for the study included age, parity, educational level, gestational age and occupation of participant. Haemoglobin electrophoresis patterns were also retrieved and recorded. Main outcome measures were prevalence of asymptomatic bacteriuria, bacterial isolates and their antibiotic sensitivities. RESULTS: There were 205 eligible participants with a mean age of 30.6 +/- 4.3 years and a mean gestational age at booking of 20.9 +/-7.0 weeks. The prevalence of asymptomatic bacteriuria was 22(10.7%). The isolated pathogens were predominantly coliforms (Klebsiella and E. coli) accounting for 45.5% and Staphylococcus saprophyticus (27.3%). Only gentamycin, nitrofurantoin and ofloxacin demonstrated high efficacy against these uropathogens with antibiotic sensitivity rates of 72.7%-81.8%. CONCLUSION: Prevalence of asymptomatic bacteriuria in this centre is relatively high. This underscores the need for routine screening of pregnant women for bacteriuria. PMID- 21984455 TI - Glycaemic response to some commonly eaten fruits in type 2 diabetes mellitus. AB - BACKGROUND: It is not known which of the commonly consumed fruits in Nigeria are suitable for persons with diabetes mellitus especially with regards to the attendant plasma glucose response (PGR) to consumption of such fruits. OBJECTIVES: To determine and compare the PGR to commonly eaten fruits in patients with diabetes mellitus. METHODS: Ten persons with type 2 diabetes mellitus were studied. Fifty-gram portions of five fruits containing 50 g carbohydrate [ banana, Musa paradisiaca; orange, Citrus sinensis; pineapple, Ananus comosus; mango, Magnifera indica; pawpaw, Carica papaya], and glucose were randomly fed to the study subjects at one-week intervals. Blood samples were collected in the fasting state and half-hourly over a 2- hour period post-ingestion of the fruits or glucose for plasma glucose determination. Plasma glucose responses were assessed by the peak plasma glucose concentration (PPPG), maximum increase in postprandial plasma glucose (MIPG), two-hour postprandial plasma glucose level (2hPG) and incremental area under the glucose curve (IAUGC). RESULTS: The mean +/ SEM PPPG in mmol/L were: banana, 9.0+/- 1.6; orange, 8.1+/- 0.8; pineapple, 9.2+/-1.1; mango, 8.0 +/- 1.1; and pawpaw, 7.8+/-0.9. The mean +/-SEM IAUGC in mmol.min/L were: banana, 131.7+/-53.4; orange, 108.7+/-29.8; pineapple, 115.3+/ 33.2; mango, 101.6 +/- 28.7; and pawpaw, 124.1+/- 46.1. However, mango showed the least MIPG (1.8 +/- 0.5 mmol/l) followed by orange and pawpaw. The IAUGC also followed this pattern. There were no significant differences among the glycaemic indices of the fruits. Glucose load produced a significantly higher IAUGC than the fruits (orange, pineapple, mango, pawpaw, p<0.005; banana, p<0.025). CONCLUSION: The plasma glucose response to consumption of Nigeria fruits are similar. The PGR indices to all fruits were less than the PGR after an equivalent carbohydrate load of glucose. It appears safe to recommend these Nigerian fruits to persons with diabetes within the prescribed daily total calorie intake. PMID- 21984456 TI - Relationship between bioelectrical impedance analysis and body mass index in adolescent urban Nigerians. AB - BACKGROUND: Body mass index is often used to assess adiposity but it does not differentiate between fat and non-fat components of body mass. However, body fat composition may be assessed using bioelectrical impedance analysis. OBJECTIVE: The study aimed to relate body mass index to fat in the assessment of overweight and obesity among adolescent Nigerians. METHODS: Adolescent pupils aged 10 years to 18 years from randomly selected secondary schools in Lagos, Nigeria were studied. Body mass index was calculated while percentage body fat was measured using Tanita body(r) fat scale model BF 681. Overweight and obesity were defined using age and sex specific criteria for body mass index and for body fat. RESULTS: There were 753 pupils {377(50.1%) males and 376(49.9%) females}. The overall mean values of body mass index for males and females were 18.1+/-2.72 and 18.9+/-3.41 (p < 0.05) respectively. The corresponding figures for body fat were 9.5+/-4.48 and 18.9+/-7.51 (p<0.05) respectively. About three quarters (76.2%) of the females who had body mass index in the overweight and obesity range had high body fat in comparison to 44.4% of males (p < 0.05). CONCLUSION: Body mass index is more related to body fat in adolescent females than in their male counterparts. PMID- 21984457 TI - African programme for Onchoceriasis control: ophthalmological findings in Bushenyi, Uganda. AB - BACKGROUND: The overall prevalence of blindness from Onchoceriasis in Bushenyi is relatively low, most of which is to be found in the elderly. Onchoceriasis is a major health problem in Africa. The Community-Directed treatment with invermectin is a control strategy to address the problem, but baseline data are generally lacking in several countries. OBJECTIVE: To describe baseline ophthalmological data in order to assess the impact of Community-Directed with Ivermectin (CDTI) in Uganda. METHODS: The study site was in Bushenyi, Western Uganda. In a cross sectional study, 367 persons aged 10 years or older from seven selected villages received eye examination using a standardised protocol and Wu-Jones Motion Sensitivity Testing (MSST). Besides MSST, other information sought included visual acuity, slit lamp examination, testicular opacities and intraocular presence. RESULTS: Of the 367 subjects, 219(57.2%) were males. Subjects less than 25 years of age were 104(28.3). The prevalence of blindness were 1.9% while 4.1% was visually impaired by acuity criteria alone. A further 9.1% had moderate visual field loss while 2.8% had severe field loss. There was no case of anterior chamber microfilaria but dead microfilariae were seen in two cases. Punctate keratitis was present in 1.8% with sclerosing keratitis was twice as common at 3.8%. Optic atrophy was also relatively common at 12.4%, while chorioretinitis was present in 3.3%. CONCLUSION: There was an apparent paucity of acute onchocerciasis-related lesions but a significant presence of irreversible onchocerciasis-related lesions. The most significant problem requiring intervention would appear to be cataract. PMID- 21984458 TI - Evaluation of tension-free mesh inguinal hernia repair in Nigeria: a preliminary report. AB - BACKGROUND: Tension-free mesh inguinal hernia repair is becoming increasingly popular worldwide. However, reports are sparse in Nigeria. OBJECTIVE: To evaluate the impact, outcome and cost implication of tension free inguinal hernia repair in a Nigerian setting. METHODS: A prospective study of all consecutive adults patients with uncomplicated inguinal hernia who had mesh repair over a period of 12 months was undertaken. A large sheet of 900cm2 polyproylene mesh material was used for all the patients in the study. All wounds were opened on the third postoperative day while sutures were removed on the eight day. Patients were followed up for one year. RESULTS: A total number of 30 patients had tension-free mesh ingunal hernia repair. Their ages ranged from 21 to 78 years (mean 47.2+/ 15.5) years with a female to male ratio of 1:15. Complete inguinoscrotal hernia was the commonest type of groin hernia accounting for 40% of the cases. The repair of posterior wall which entailed placement of mesh was completed at a median time of 15 minutes. While two (6.7%) and one (3.3%) had wound oedema and groin pain respectively at one month, none of the patients had these complications or recurrence at a median of five months follow-up period. CONCLUSION: Tension-free mesh inguinal hernia repair was well tolerated and affordable to our patients. Pain and infections, reported to be the common complications of this procedure were infrequent in this study. A larger study is recommended to help confirm these findings. PMID- 21984459 TI - Oro-dental and maxillofacial trauma in epilepsy at a tertiary hospital in Lagos. AB - BACKGROUND: Seizure-related injuries are common and are a major cause of morbidity in subjects with epilepsy. OBJECTIVE: To determine the frequency and types of oro-facial injuries in epileptic patients attending a tertiary hospital. METHODS: A structured questionnaire was used to obtain information about injuries to the oral and maxillofacial region in epileptic patients at the Neurology Clinic of the Lagos University Teaching Hospital over a period of two years. Information sought included patient's sociodemographics, type of seizure, self management of seizures, and history of injuries during seizures. RESULTS: Of the 138 epileptic patients seen, 87 (63.0%) reported the occurrence of oral and maxillofacial injuries. Mean age of these patients (29.6+/-12.1 years) was not significantly different from that of those who had no injuries (33.5+/-15.6 years). Prevalence of seizure-related injuries was not significantly different in males and females (50 [58.8%] vs 37 [71.2%]). Injuries were more likely in those who had convulsive seizures than in those who had non-convulsive seizures. Patients who had hard objects forced between their clenched teeth during seizure episodes were more likely to sustain injuries. Soft tissue injuries were more common than injuries to the facial bones and teeth. Of these, the tongue was the most commonly injured. Majority of those with soft tissue injuries did not receive treatment in hospital. Although fractures of the cheek and jaw bones were not so common, all such cases received surgical treatment in hospital. CONCLUSION: A high proportion of epileptic patients in Lagos appear to suffer seizure-related oro-facial injuries. Measures for the prevention and management of these injuries are needed to help reduce the morbidity caused by such injuries. PMID- 21984460 TI - Visual morbidities among elderly patients presenting at a primary care clinic in Nigeria. AB - BACKGROUND: Visual challenges compromise mobility, increase dependency on family members and constitute a major health problem mainly seen by the primary care physicians among the elderly. However, there is little information on the pattern of visual problems of elderly patients attending the primary care clinics in Nigeria. OBJECTIVE: To describe the visual problems among elderly subjects in a hospital setting. METHODS: Five hundred consecutive patients (311 females and 189 males) aged 60 years and above were interviewed using a structured questionnaire based on the World Organization of Family Doctors (Wonca) format between September 2004 and April 2005. The main outcome measurements were sociodemographic characteristics, visual acuity and ocular problems. RESULTS: The main visual problems reported by the elderly were impaired vision 224 (44.8%) and abnormal sensations in the eyes 64 (12.8%). Cataract 198 (39.7%) was the commonest eye disorder diagnosed by the Family Physician, followed by pterygium 32 (6.4%). Assessment of binocular acuity revealed blindness in 109 (21.8%) and low-vision in 68 (13.6%). The prevalence of visual impairment increased significantly with age. CONCLUSION: Visual impairment is a common problem of the elderly people in the hospital setting, with cataract being the main cause. Efforts should be made to detect these conditions early and institute treatment promptly. PMID- 21984461 TI - Negative pressure pulmonary oedema following adenoidectomy under general anaesthesia: a case series. AB - BACKGROUND: Negative pressure pulmonary oedema (NPPE) is a potentially life threatening complication of laryngospasm that occurs during or after general anaesthesia. It is a complication of poorly treated or unrecognized laryngospasm occurring at extubation or later in the postoperative period. OBJECTIVE: To emphasize prompt recognition of laryngospasm during or after general anaesthesia and to prevent its progression to NPPE in a resource-challenged environment. METHODS: Three children aged two to four years, one of whom was a known sickle cell anaemia patient presented with adenoid hypertrophy. Surgery was postponed on account of upper respiratory tract infection in each of them. RESULTS: Following treatment of upper respiratory tract infection, they had adenoidectomy under general anaesthesia. They all developed severe laryngospasm at extubation. This progressed to NPPE which was diagnosed on clinical parameters. The children were subsequently admitted to the intensive care unit (ICU) for mechanical ventilation with high FiO2 (0.7-1) and PEEP between 12-24hours. While two of the children survived, the child with sickle cell anaemia died in the ICU. CONCLUSION: Negative pressure pulmonary oedema is a self limiting complication of laryngospasm if it is well managed. However, its outcome may not be good in a patient with intercurrent medical illness such as sickle cell anaemia in which hypoxaemia is deleterious. PMID- 21984462 TI - Isolation and molecular identification of Fusobacterium nucleatum from Nigerian patients with oro-facial infections. AB - BACKGROUND: Fusobacterium nucleatum is one of the most common anaerobic bacteria present in the oral cavity and is often isolated from infections involving other body sites. OBJECTIVE: To characterise F. nucleatum strains from patients attending a teaching hospital in Nigeria in order to provide information on the methods for accurate identification of anaerobes in clinical specimen. METHODS: Fusobacterium nucleatum specie from 50 patients presenting with oro-facial infections were studied by culture on Fusobacterium selective agar and fastidious anaerobe agar. The isolates were characterised based on colonial morphology, microscopy, lipase production, susceptibility to kanamycin and colistin and resistance to vancomycin. Biochemical tests were performed using a commercial test kit. The identity of the isolates was confirmed based on molecular characterization performed using polymerase chain reaction (PCR) analysis. RESULTS: Forty-eight (96%) F. nucleatum isolates were obtained from the 50 patients by culture and all the isolates were identified by colonial appearance and microscopy based on their unique spindle shape with tapered ends. Only 26 (54.2%) of the 48 isolates were identified by commercial API 20A test kit while PCR confirmed the identity of all the isolates. CONCLUSION: Anaerobes are involved in human infections and their study is quite cumbersome due to tedious nature and high cost of the techniques involved. Cultural method is reliable in the isolation and identification of F. nucleatum species. PCR is a rapid and simple method that can complement the phenotypic identification of anaerobes and would assist in their full identification. PMID- 21984463 TI - Profile and outcome of unilateral tuberculous lung destruction in Ilorin, Nigeria. AB - BACKGROUND: Unilateral tuberculous lung destruction is a serious chronically disabling and often fatal complication of pulmonary tuberculosis. A few previous studies have dealt with some aspects of this entity among Nigerians with pulmonary tuberculosis but these studies may not truly reflect its current trends. OBJECTIVE: To describe the presenting profiles and outcome of unilateral tuberculous lung destruction among patients with pulmonary tuberculosis. METHODS: The study was a chart review of the medical records of adult patients with pulmonary tuberculosis complicated by unilateral lung destruction seen between January 1999- December 2008. Data extracted included demographic, and outcome of treatment. The clinical features, sputum results and illustrative cases are presented. RESULTS: Unilateral lung destruction complicated 74(1.3%) of 5,926 pulmonary tuberculosis cases seen over the review period. Most cases occurred in males [45(60.8%)] and they were predominantly [51(68.9%)] below 40 years of age. Most of them [52(70.2%)] presented after six months of symptoms. Forty-seven (63.5%) of them had had previous exposure to antituberculosis drugs. The left lung was affected in 49 (66.2%) patients. Only 25 (33.8%) of them were cured while the adjusted mortality rate was 25.5%. Male gender, presence of dyspnoea on mild exertion and right ventricular failure were significantly associated with increased mortality. CONCLUSION: Unilateral tuberculous lung destruction has unacceptably high mortality rate which can be prevented by patient presenting early to the hospital, prompt diagnosis and strict adherence to the standard treatment. PMID- 21984464 TI - Acute retrocaecal appendicitis: a case report. AB - BACKGROUND: Acute abdomen is a clinical diagnosis and not a definitive one. The use of ultrasound in management and diagnosis of acute abdomen is rarely invoked in our environment. The importance of definite diagnosis in surgical and medical management cannot be overemphasized OBJECTIVE: To report a case of ultrasound diagnosis of retrocaecal appendicitis. METHODS: A nine-year-old male child presented with vomiting, vague abdominal pain, diarrhoea, and fever, which led to the following differential diagnoses; acute food poison gastro-enteritis, typhoid enteritis, malaria and acute appendicitis. He was investigated along these lines. He had abdominal ultrasonography and CT scan . RESULTS: The ultrasound showed evidence of acute appendicitis. The findings on CT and surgery confirmed the diagnosis. Post-operatively, he made uneventful recovery. CONCLUSION: The use of ultrasound in acute abdomen is rarely invoked in our environment which may lead to unquantifiable consequences both in management and complications. PMID- 21984465 TI - Alternating hemiplegia in a child misdiagnosed as intractable epilepsy successfully treated with aripiprazole: a case report. AB - BACKGROUND: Alternating hemiplegia of children is a rare neurological disorder that in its characteristic form has few differential diagnosis. The diagnosis of intractable seizures is difficult to avoid for physicians not aware of the disease. OBJECTIVE: To describe the clinical characteristics of Alternating Hemiplegia of Childhood (AHC), and response to various drugs METHODS: A Ghanaian child with AHC was followed up for three years at the Neurology Clinic, Korle Bu Teaching Hospital, Accra. Her characteristics including EEG and MRI findings were documented. She was severely unsuccessfully treated as an epileptic. Further clinical re-evaluation provided clues to the diagnosis of alternating hemiplegia of childhood. RESULTS: The child, a female patient, was seen within the first week of life. The initial complaints were abnormal eye movements, and subsequently recurrent hemiplegic episodes, that started at age two and lasted hours to days. Attacks occurred at a frequency of about three per month and lasted from several hours to three days. An established trigger was bathing with cold water. Sleep relieved symptoms. The child had evidence of global developmental delay and neurological abnormalities including ataxia. EEG and MRI were both reported as abnormal. She experienced recurrent seizures. Topiramate and several anti-convulsants were not helpful but aripiprazole reduced the frequency of attacks. CONCLUSION: The case highlights the fact that AHC starts very early in life and is commonly misdiagnosed as epilepsy .It can coexist with epilepsy and abnormal MRI findings. Aripiprazole appears effective in its treatment. PMID- 21984466 TI - Relationship between health-related quality of life and clustering of metabolic syndrome diagnostic components. AB - PURPOSE: To examine the association of the number of metabolic syndrome diagnostic components (MetS-DC) with health-related quality of life (HR-QOL). METHODS: We examined the baseline data from 4,480 healthy workers in Japan (3,668 men and 812 women) aged 19-69 years. We assessed HR-QOL based on scores for five scales of the SF-36. We defined four components for MetS in this study as follows: (1) high blood pressure (BP); (2) dyslipidemia; (3) impaired glucose tolerance; and (4) overweight: a body mass index >=25 kg/m(2). Logistic regression analysis adjusted for lifestyle factors was used to examine the association of the number of MetS-DC with the HR-QOL sub-scales. RESULTS: Those who had 0-4 MetS-DC accounted for 2,287, 1,135, 722, 282, and 54 participants. The number of MetS-DC inversely contributed significantly to General Health (norm based scoring >50) (odd ratios [OR] 0.59-0.82, P < 0.05) and positively associated with Mental Health (OR 1.37, P < 0.05). CONCLUSION: When adjusted for lifestyle factors, the number of MetS-DC was inversely associated with General Health and positively with Mental Health in men and women. PMID- 21984467 TI - Validation of the Swedish translation of the General Self-Efficacy scale. AB - PURPOSE: To study the internal consistency, factorial structure, and convergent validity of the Swedish translation of the General Self-Efficacy scale (S-GSE). METHODS: The S-GSE and two items on mental and physical work capacity were completed by a randomized population cohort (n = 4,027) and two cohorts (n = 3,310 and n = 498) of incident cases of sick-leave (>14 days). RESULTS: S-GSE means were higher among men than women in two of the cohorts and higher in the randomized population cohort than in the two sick-leave cohorts. Internal consistency was high with alpha = .90. Unidimensionality was indicated and factor loadings ranged between .64 and .80. Moderate correlations (.35-.38) between the S-GSE and mental work capacity were found in all cohorts. Yet, the correlation between S-GSE and physical work capacity was weaker in the sick-leave cohorts. The psychometric properties showed similar patterns across gender. CONCLUSIONS: Across three cohorts, additionally stratified by gender, the S-GSE comprised one single latent factor and showed high internal consistency. However, since S-GSE was more strongly related to self-assessments of mental work capacity than physical work capacity regardless of sick-leave status, the S-GSE may not be a strong predictor of beliefs about physical work capacity across all populations. PMID- 21984468 TI - Reliability of adverse symptom event reporting by clinicians. AB - PURPOSE: Adverse symptom event reporting is vital as part of clinical trials and drug labeling to ensure patient safety and inform risk-benefit decision making. The purpose of this study was to assess the reliability of adverse event reporting of different clinicians for the same patient for the same visit. METHODS: A retrospective reliability analysis was completed for a sample of 393 cancer patients (42.8% men; age 26-91, M = 62.39) from lung (n = 134), prostate (n = 113), and Ob/Gyn (n = 146) clinics. These patients were each seen by two clinicians who independently rated seven Common Terminology Criteria for Adverse Events (CTCAE) symptoms. Twenty-three percent of patients were enrolled in therapeutic clinical trials. RESULTS: The average time between rater evaluations was 68 min. Intraclass correlation coefficients were moderate for constipation (0.50), diarrhea (0.58), dyspnea (0.69), fatigue (0.50), nausea (0.52), neuropathy (0.71), and vomiting (0.46). These values demonstrated stability over follow-up visits. Two-point differences, which would likely affect treatment decisions, were most frequently seen among symptomatic patients for constipation (18%), vomiting (15%), and nausea (8%). CONCLUSION: Agreement between different clinicians when reporting adverse symptom events is moderate at best. Modification of approaches to adverse symptom reporting, such as patient self reporting, should be considered. PMID- 21984470 TI - Removing material using atomic force microscopy with single- and multiple-tip sources. AB - Atomic force microscopy (AFM) has been an effective material removing tool for fabricating various nanostructures because of its sub-nanometer precision and simplicity in operation. AFM material removing techniques have evolved from a solely mechanical process to one in which the tip can be loaded by additional energy sources, such as thermal, electric, or chemical, to enhance its fabrication abilities. In this paper, these material removing techniques are reviewed with an emphasis on their capabilities and recent progress. The recent hardware and software developments are first presented to provide a general view on the current status of the technology to be assessed. Following an overview of the feasibility and effectiveness of using mechanical scratching for removing various types of soft and hard materials, the processes of a wide range of approaches using multiple tip sources are then assessed with a focus on their principles, versatilities, and potentials for future applications. PMID- 21984471 TI - Gender-dependent cancer-specific survival following radical cystectomy. AB - OBJECTIVE: To assess the impact of detailed clinical and histopathological criteria on gender-dependent cancer-specific survival (CSS) in a large consecutive series of patients following radical cystectomy (RCE) for muscle invasive bladder cancer (MIBC). PATIENTS AND METHODS: Between 1992 and 2007, 388 men and 133 women (25.5%) underwent RCE for MIBC. A prospectively maintained database was analysed retrospectively. Uni- and multivariable Cox-regression analyses calculated the impact of detailed clinical and histopathological criteria on CSS. Median follow-up was 59 months (2-162). RESULTS: Among clinical and histopathological parameters, only type of urinary diversion differed between men and women. In univariable analysis, CSS did not differ between genders. In multivariable Cox-regression analysis, advanced pT-stage (HR = 2.12; P < 0.001), lymphovascular invasion (LVI) (HR = 3.47; P < 0.001), time interval between diagnosis of MIBC and RCE exceeding 90 days (HR = 2.07; P < 0.001) and female gender (HR = 1.35; P = 0.048) were related to reduced CSS. In separate multivariable Cox-models for time period of surgery between 1992 an 1999 (HR = 1.52; P = 0.050), age <=55 years (HR = 3.00; P = 0.022), presence of LVI (HR = 1.45; P = 0.031) and female gender were associated with independent reduced CSS. CONCLUSION: Established clinical and histopathological parameters do not differ significantly between both genders in the present series. Reduced CSS in women is present in historic cohorts possibly suggesting improvement in management over the last years. In particular, female gender has a significant negative impact on CSS in patients younger of age and with positive LVI status possibly suggesting different clinical phenotypes. PMID- 21984469 TI - Mastitis therapy and antimicrobial susceptibility: a multispecies review with a focus on antibiotic treatment of mastitis in dairy cattle. AB - Mastitis occurs in numerous species. Antimicrobial agents are used for treatment of infectious mastitis in dairy cattle, other livestock, companion animals, and humans. Mastitis is an economically important disease of dairy cattle and most mastitis research has focused on epidemiology and control of bovine mastitis. Antibiotic treatment of clinical and subclinical mastitis in dairy cattle is an established component of mastitis control programs. Research on the treatment of clinical and subclinical mastitis in other dairy species such as sheep and goats has been less frequent, although the general principles of mastitis therapy in small ruminants are similar to those of dairy cattle. Research on treatment of clinical mastitis in humans is limited and as for other species empirical treatment of mastitis appears to be common. While antimicrobial susceptibility testing is recommended to direct treatment decisions in many clinical settings, the use of susceptibility testing for antibiotic selection for mastitis treatments of dairy cattle has been challenged in a number of publications. The principle objective of this review is to summarize the literature evaluating the question, "Does antimicrobial susceptibility predict treatment outcome for intramammary infections caused by common bacterial pathogens?" This review also addresses current issues related to antimicrobial use and treatment decisions for mastitis in dairy cattle. Information on treatment of mastitis in other species, including humans, is included although research appears to be limited. Issues related to study design, gaps in current knowledge and opportunities for future research are identified for bovine mastitis therapy. PMID- 21984472 TI - The result of adjuvant chemotherapy for localized pT3 upper urinary tract carcinoma in a multi-institutional study. AB - PURPOSE: To determine through the analysis of our multi-institutional database whether postoperative adjuvant chemotherapy for upper urinary tract carcinoma with localized invasive upper urinary tract carcinoma (UUTC) is beneficial. METHODS: A study population of 93 patients with pT3N0/xM0 UUTC was eligible for this study. Clinical features evaluated were sex, tumor location, adjuvant chemotherapy status, tumor pathology (histology, grade, infiltrating growth, lymphovascular invasion (LVI)), and cause of death. Cancer-specific survival (CSS) was estimated by Kaplan-Meier method. Prognostic factors related to CSS were analyzed by Cox proportional hazards regression model for multivariate analysis. RESULTS: In pT3 patients, overall 5-year CSS rate was 68.4% and median CSS time was 31 months (range 3-114 months). In the adjuvant chemotherapy group, 5-year CSS rate was 80.8%, whereas 5-year CSS rate was 64.4% in the non-adjuvant chemotherapy group. By multivariate analysis, adjuvant chemotherapy status was significantly associated with CSS (P = 0.008) were sex, tumor grade, tumor histology, and LVI presence. CONCLUSIONS: This study, although it was retrospective study, revealed that adjuvant chemotherapy after RNU may be beneficial in pT3N0/X patients by multivariate analysis. Prospective studies evaluating adjuvant therapy regimens for UTTC are required. PMID- 21984473 TI - Pelvic floor muscle training in treatment of female stress urinary incontinence, pelvic organ prolapse and sexual dysfunction. AB - OBJECTIVES: The objectives of the present review was to present and discuss evidence for pelvic floor muscle (PFM) training on female stress urinary incontinence (SUI), pelvic organ prolapse (POP) and sexual dysfunction. METHODS: This manuscript is based on conclusions and data presented in systematic reviews on PFM training for SUI, POP and sexual dysfunction. Cochrane reviews, the 4th International Consultation on Incontinence, the NICE guidelines and the Health Technology Assessment were used as data sources. In addition, a new search on Pubmed was done from 2008 to 2011. Only data from randomized controlled trials (RCTs) published in English language is presented and discussed. RESULTS: There is Level 1, Grade A evidence that PFM training is effective in treatment of SUI. Short-term cure rates assessed as <2 g of leakage on pad testing vary between 35 and 80%. To date there are 5 RCTs showing significant effect of PFM training on either POP stage, symptoms or PFM morphology. Supervised and more intensive training is more effective than unsupervised training. There are no adverse effects. There is a lack of RCTs addressing the effect of PFM training on sexual dysfunction. CONCLUSIONS: PFM training should be first line treatment for SUI and POP, but the training needs proper instruction and close follow-up to be effective. More high quality RCTs are warranted on PFM training to treat sexual dysfunction. PMID- 21984474 TI - Canalicular ABC transporters and liver disease. AB - Bile is a complex mixture that includes bile salts, the membrane phospholipid phosphatidylcholine (PC), cholesterol and various endobiotic and xenobiotic toxins, each of which is secreted across the canalicular membrane of the hepatocyte by different ATP-binding cassette (ABC) transporters. The bile salts are essential for the emulsification of dietary fat and lipophilic vitamins. They are synthesized from cholesterol in the hepatocyte and their secretion by the bile salt export pump (BSEP or ABCB11) drives bile flow and is the starting point for the enterohepatic cycle. The detergent nature of bile salts that is key to their physiological role also means that they are inherently cytotoxic, and failure to secrete bile (intraheptic cholestasis) can precipitate severe liver disease and mortality. Such progressive familial intrahepatic cholestasis (PFIC) comes in three types of autosomal recessive disease. PFIC2 is caused by mutation to ABCB11. PFIC3 is caused by mutation of a closely related ABC transporter, ABCB4, which flops PC into the outerleaflet of the canalicular membrane. The flopped PC is extracted by the bile salts in the canaliculus to form a mixed micelle that reduces bile salt detergent activity. The third protein that is essential for bile flow from the hepatocyte is a member of a different class of transporter protein, a P-type ATPase, ATP8B1. Mutation of ATP8B1 causes PFIC1, but ATP8B1 does not transport a component of bile into the canaliculus. Data from different laboratories, published this year, suggests two different roles for ATP8B1 in the hepatocyte: a lipid flippase, that counterbalances the deleterious effects of ABCB4 on barrier function of the canalicular membrane; and an anchor of the actin cytoskeleton necessary to form the microvilli of the brush border. These latest discoveries are described, along with a spectrum of cholestatic disorders whose aetiologies lie in these and other transporters of the canalicular membrane. PMID- 21984475 TI - NAPP: the Nucleic Acid Phylogenetic Profile Database. AB - Nucleic acid phylogenetic profiling (NAPP) classifies coding and non-coding sequences in a genome according to their pattern of conservation across other genomes. This procedure efficiently distinguishes clusters of functional non coding elements in bacteria, particularly small RNAs and cis-regulatory RNAs, from other conserved sequences. In contrast to other non-coding RNA detection pipelines, NAPP does not require the presence of conserved RNA secondary structure and therefore is likely to identify previously undetected RNA genes or elements. Furthermore, as NAPP clusters contain both coding and non-coding sequences with similar occurrence profiles, they can be analyzed under a functional perspective. We recently improved the NAPP pipeline and applied it to a collection of 949 bacterial and 68 archaeal species. The database and web interface available at http://napp.u-psud.fr/ enable detailed analysis of NAPP clusters enriched in non-coding RNAs, graphical display of phylogenetic profiles, visualization of predicted RNAs in their genome context and extraction of predicted RNAs for use with genome browsers or other software. PMID- 21984476 TI - Rational design of a small molecule-responsive intramer controlling transgene expression in mammalian cells. AB - Aptamers binding proteins or small molecules have been shown to be versatile and powerful building blocks for the construction of artificial genetic switches. In this study, we present a novel aptamer-based construct regulating the Tet Off system in a tetracycline-independent manner thus achieving control of transgene expression. For this purpose, a TetR protein-inhibiting aptamer was engineered for use in mammalian cells, enabling the RNA-responsive control of the tetracycline-dependent transactivator (tTA). By rationally attaching the theophylline aptamer as a sensor, the inhibitory TetR aptamer and thus tTA activity became dependent on the ligand of the sensor aptamer. Addition of the small molecule theophylline resulted in enhanced binding to the corresponding protein in vitro and in inhibition of reporter gene expression in mammalian cell lines. By using aptamers as adaptors in order to control protein activity by a predetermined small molecule, we present a simple and straightforward approach for future applications in the field of Chemical Biology. Moreover, aptamer-based control of the widely used Tet system introduces a new layer of regulation thereby facilitating the construction of more complex gene networks. PMID- 21984477 TI - Genomic risk variants at 1p13.3, 1q41, and 3q22.3 are associated with subsequent cardiovascular outcomes in healthy controls and in established coronary artery disease. AB - BACKGROUND: Genome-wide association studies have identified gene variants associated with coronary artery disease risk; however, whether they affect disease progression is largely unknown. This study investigated associations between polymorphisms at 1p13.3 (rs599839), 1q41 (rs17465637), and 3q22.3 (rs9818870) and cardiovascular outcomes in healthy volunteers and in patients with established heart disease. METHODS AND RESULTS: Canterbury Healthy Volunteer study (HV) (n=1649), Coronary Disease Cohort Study (CDCS) (n=1797), and Post Myocardial Infarction study (PMI) (n=906) participants (New Zealand), were genotyped for rs599839, rs9818870, and rs17465637. Associations between genotype and anthropometric characteristics, neurohormonal analysis, echocardiography, and clinical outcomes over medium-long-term follow-up (median HV, 5.9 years; CDCS, 3.7 years; PMI, 11.3 years) were tested. At 1p13.3, HV and CDCS participants carrying 1 or more rs599839 G allele had a lower prevalence of dyslipidemia (P <= 0.005) or lower levels of low-density lipoprotein (P=0.031) and total (P=0.004) cholesterol and/or less history of myocardial infarction (P <= 0.04) compared with AA participants. Moreover, CDCS and PMI AG/GG participants had better cardiac function as indicated by echocardiography (P <= 0.026), and fewer CDCS AG/GG participants were readmitted for a non-ST-segment elevation MI (P=0.012) during follow-up. The polymorphism at 1q41 (rs17465637) was associated with better cardiovascular outcomes in the HV (P=0.028) and PMI (P=0.008) cohorts, and 3q22.3 (rs9818870) was a predictor of death/admission in the HV cohort (P=0.045). CONCLUSIONS: These data suggest that coronary artery disease genomic risk variants at 1p13.3 and 1q41 are associated with subsequent clinical outcome in heart patients and confirm rs9818870 at 3q22.3 as a predictor of cardiovascular risk in individuals free of overt heart disease. PMID- 21984478 TI - Association of known loci with lipid levels among children and prediction of dyslipidemia in adults. AB - BACKGROUND: Recent genome-wide association studies have found 95 distinct genetic loci associated with high-density (HDL-C) and low-density (LDL-C) lipoprotein cholesterol, total cholesterol (TC), and triglycerides (TG), using adult samples. It is not known if these variants are associated with lipid levels in children and adolescents and if the genetic risk score (GRS), based on these variants, could improve adulthood dyslipidemia prediction over the childhood lipid measurements. METHODS AND RESULTS: We used 2443 participants of the Cardiovascular Risk in Young Finns study cohort with up to 5 measurements of serum lipids taken between ages 3 and 45 years to estimate the effect of individual single-nucleotide polymorphisms and the GRS on lipids. The GRSs were strongly associated with lipids in all age groups (1.5 * 10(-20)